SYNTHESIS WITH THIO SUGARS - OhioLINK ETD

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BELL, Reuben Hays, 1942- SYNTHESIS WITH THIO SUGARS: FORMATION AND DECOMPOSITION OF ACETYLATED GLYCOSYLSULFENYL BROMIDES.

The Ohio State University, Ph.D., 1969 Chemistry, organic

University Microfilms, Inc., Ann Arbor, Michigan

SYNTHESIS WITH THIO SUGARS:

FORMATION AND DECOMPOSITION OF ACETYLATED

GLYCOSYLSULFENYL BROMIDES

DISSERTATION

P resen ted in P a r t i a l F u lf i llm e n t of th e Requirements fo r the Degree Doctor o f Philosophy in th e Graduate

School o f The Ohio S ta te U n iv e rs ity

By

Reuben Hays B e l l , B .S ., M,S

The Ohio S ta te U n iv e rs ity 1969

Approved by

A dviser Department of Chemistry

DEDICATION

To my m other, Alma Hays B e ll , and

my l a t e f a th e r , Duane H a z le tt B e ll .

ii

ACKNOWLEDGMENTS

The au tho r thanks Dr. Derek Horton fo r h is guidance and

advice throughout t h i s re se a rc h . The au tho r a lso i s ind eb ted to

th e U nited S ta te s Department of A g ricu ltu re fo r f in a n c ia l support

under g ra n ts No. 12-14-100-7208 (71) and 12-14-9201 (71)

(O .S.U .R.F. P ro je c ts 1827 and 2573). The au tho r thanks h is w ife ,

K aren, fo r p a tien c e and understand ing throughout h is g raduate

c a re e r . Many thanks a re due to P h ilip p e D u re tte , John L auterbach ,

and Joseph Wander fo r a s s is ta n c e w ith th e n .m .r . sp e c tra and to

th e o th e r members o f th e re se a rc h group fo r h e lp fu l d iscu ss io n s

throughout t h i s re sea rch p ro je o t .

i i i

VITA

A p ril 24, 1 9 4 2 ...............................Born - L am artine, Pennsylvania

I 964. .....................................................B .S . , Grove C ity C o llege,Grove C ity , Pennsylvania

I 964- I 966 ............................................ Teaching A s s is ta n t , Department ofC hem istry, The Ohio S ta te U n iv e rs ity , Columbus, Ohio

1966-1969 ............................................ Graduate Research A sso c ia te ,Department o f C hem istry, The Ohio S ta te U n iv e rs ity , Columbus, Ohio

1967 . . . . . . M .S ., The Ohio S ta te U n iv e rs ity ,Columbus, Ohio

PUBLICATIONS

R. H. B e ll , D. H orton , and Diana M. W illiam s, "P h o to ly s is o f D im ethylth iocarbam ates as a Route t o D eoxy-sugars," Chera. Commun., 323 (1968).

R. H. B e ll and D. H orton, "The Action o f Bromine on T etra-O -A cetyl- 1 -S -A cety l-l-T hio-p-D -G lucopyranose. Form ation and Decomposition o f T etra-O -ace ty l-p -D -G Iucopyranosy lsu lfeny l Brom ide," Carbohyd. R es., 2 , 187 (1969). “

R. H. B e ll , D. H orton , and M artha J . M il le r , "R eactions of T e tra -O -A cetyl-B -D -G lucopyranosylsulfenyl Bromide," Carbohyd. R e s ., 2*201 (1969 ).“

FIELDS OF STUDY

Major F ie ld : Organic Chem istry

iv

TABLE OF CONTENTS

Page

DEDICATION........................................... i i

ACKNOWLEDGMENTS.......................................................................... l i i

VITA ............................................. ivLIST OF TABLES.............................................................. v i i

LIST OF FIG U R ES..................................... v i i i

LIST OF ILLUSTRATIONS............................................ ix

INTRODUCTION AND STATEMENT OF THE PROBLEM.................. 1

HISTORICAL ................................................................................... . 3

A. N a tu ra lly o ccu rrin g 1 -th io -D -g l u c o s id e s ....................................................................... 4.

B. S yn thesis o f a c e ty la te d 1-th io g ly c o s id e s and a c e ty la te d1 - th io sugars 13

C. S yn thesis o f 1 - th io g lu c o s id e s bya c id -c a ta ly z e d g ly c o s id a t io n .. 22

D. Form ation and r e a c t i v i ty o f t e t r a -O -ace ty l-p -D -g lucopyranosy l-s u lfe n y l bromide • • • • * • • • • « * 27

E. Photochem istry of carbohydrates . . . . 31

RESULTS AND DISCUSSION

A. A cety la ted g ly co sy l h a l i d e s ..........................

B. P re p a ra tio n o f 2 -g ly c o sy l-2 -th iopseudourea hy d ro h alid es 43

C. P e ra c e ty la te d 1 - th io su g a rs • • • • • • • 48

v

TABLE OF CONTENTS (Continued)

Page

D. T e tra -O -ace ty l-p -D -g lucopy ranosy ls u lfe n y l bromide ................................................ 52

E. N.m*r, s p e c tra l s tu d ie s o f th ebrom ination of v a rio u s a c e ty la te d 1 - th io a ld o s e d e r iv a tiv e s incarbon te t r a c h lo r id e .................. . . . . 55

F. Form ation o f b i s ( t e t r a - 0 - a c e ty l - p -D -glucopyranosyl) d is u l f id e (2^)and b is ( te tra -O -a c e ty l-p -D -g lucopyranosy l) d is u l f id e ”mono-oxide (^0 ) 63

G. Extended brom ination o f 1 - th iosu g a r d e r i v a t i v e s ....................................... . 67

H. R eaction of te tra -O -a c e ty l-p -D -g lu co p y ran o sy lsu lfen y l bromide(2 2 ) -with e le c t ro n - r ic h c e n te rs . . . . 67

I . R eaction of p e ra c e ty la te d 1 - th iosugars w ith bromine and i s o la t io n o f tra p p in g p roducts ............................... 72

J . P h o to ly s is o f sugar th iocarbam ates . . . . go

K. N .m .r. s p e c t r a l s tudy o f deoxys u g a r s ......................................................................

EXPERIMENTAL

P a r t A: 1-Thio s u g a r s ................................................ 95

P a rt B: P h o to ly sis of su g a r th io carbam ates ................................................ I 5I

APPENDIXA. F igu res 1 - 8 ............................................................... 172-179

B, O rig in a l C o n trib u tio n s to Chem istry . . . 180

v i

LIST OF TABLES

Table Page

1 . Groups Common to Amino Acids and M ustard-O il D -glucosides ............................................ . . . . . 10

2 . Groups Found on M ustard-O il D -glucosidesn o t Common to Amino Acids 7 .......................................... 11

3 . Energy Values fo r S in g le Bonds ...................... 32

4 . A ce ty la ted G lycosyl Bromides ............................................. 42

5 . 2-G lycosyl-2-T hiopseudourea H ydrohalides . . . . . 44

6 . P e ra c e ty la te d - l-T h io Sugars ...................... 49

7 . D im ethylth iocarbam ates of Sugars .................................... 82

8 . Chemical S h i f t Data f o r 1-T hio D eriv a tiv es . . . . 167

9 . F irs t-O rd e r C oupling-C onstants fo r1-Thio D eriv a tiv es . . ..................................................... 168

10. Chemical S h if t Data f o r Deoxy S u g a r s .......................... 169

11, F irs t-O rd e r C oupling-C onstants fo rDeoxy S u g a r s .......................................................................... 170

v i i

LIST OF FIGURES Figure Page1. The i . r . sp e c tra (KBr p e l l e t ) o f te t r a -O -a c e ty l-

p rP -g lu co p y ran o sy lsu lfen y l bromide (22y , b is - ( t e t r a - 0 -acety l-p -!> -g lucopyranosy l) d is u lf id e (24 ) , and b is ( t e t r a - 0 -ace ty l-p -j> g lu c o p y ran o sy l d is u l f id e mono-oxide (30) .......................... . . . . . 172

2 . P a r t ia l n .m .r . spectrum o f phenyl t r i - O -a c e ty l-p-jD-xylopyranosyl d is u l f id e ( 3 9 ) ............................... 173

3 . P a r t ia l n .m .r . spectrum o f phenyl t r i -O -a c e ty l-a -L -arab inopy ranosy l d is u l f id e (41) ........................... 174

4 . N .m .r. spectrum o f phenyl te t r a -0 - a c e ty l - pg a lac to p y ran o sy l d is u l f id e (4-3"5 • .................. 175

5. N .m .r. spectrum o f th e crude re a c tio n producto f te tra -O -a c e ty l-a -D -g lu c o p y ra n o sy lsu lfe n y lbromide (25) and b e n z e n e th io l.................................................176

6 . N .m .r. spectrum o f 3“d o o x y - l ,2 :5 ,6 -d i-0 - is o -p ropy lidene-a -D -ribo -hoxo fu ranose (49) ...................... 177

7 . N .m .r. spectrum of 6 -d e o x y - l ,2 :3 ,4 -d i-0 - is o -p ropy lidene-a -D -galac topy ranose (56)- ................................178

8 . N .m .r. spectrum o f 1 ,6-anhydro-4-deoxy-2 ,3 -0 -isopropylidene-B -D -ly xo -hexopyranose (59) . . . . 179

v i i i

LIST OP ILLUSTRATIONS

Sch em e P a g e

I . M echanistic r a t io n a le fo r fo rm ation of t e t r a -O -a ce ty l-p -g -g lu co p y ran o sy lsu lfen y l bromide and te tra -O -ace ty l-a -D -g lu co p y ran o sy l bromide ...........................~ . . . . . . 5U

I I . Formation o f b is(tetra-0-acety l-*p-D **glucopyranosy l) d is u lf id e and b i s ( t e t r a - 0- ace ty l-p -D -g lucopy ranosy l d is u lf id e m o n o -o x id e .......................................................................... 65

I I I . High tem pera tu re (105°) r e a c t io n of t e t r a -O -ace ty l-p -D -^ lucopy ranosy lsu lfeny l bromide and- N ,N -d im ethy lan iline ............................... 71

IV, Form ation o f phenyl tr i-O -a c e ty l-p -D - xylopyranoqyl d is u l f id e and benzy l“ tr i-O -a ce ty l-p -D -x y lo p y ra n o sy ld is u lf id e . 74.

V. P re p a ra tio n o f 3 -d e o x y -ll 2 :5 ,6 -d i-0 - i3 o - p ropy lidene-a-D -r ib o -hexofuranose and 3 -deoxy-l,2-0-isopropylidene-< x-D -r ib o -hexofuranose by a known r o u t e ..................... 86

ix

INTRODUCTIONAND

STATEMENT OF THE PROBLEM

This p ro je c t was p lanned as p a r t o f a major s tudy on th e

r e a c t iv i ty w ith halogen of p ro te c te d l - th io a ld o s e sugars having

v a rio u s s u b s t i tu e n ts on th e s u l f u r atom, and to exp lo re th e re a c

t io n as a fu n c tio n of th e s u b s t i tu e n t a t th e s u lfu r atom and th e

n a tu re o f th e g ly co sy l group. The stu d y was in ten d ed , in p a r t , to

ex tend our knowledge o f a c e ty la te d g ly c o sy lsu lfe n y l bromides as

r e la te d t o t h e i r u t i l i t y and scope in sy n th e s is o f pharm aco log ica lly

im portan t compounds. A f u r th e r ex ten sio n o f th e program was p o in te d

toward ex p lo rin g s im ila r re a c t io n s in which th e s u l fu r atom was l o

ca ted on carbon atoms o th e r th an C -l o f an a ld o se su g ar. When th e

s u lfu r atom i s lo c a te d a t C -l of an a ldose i t i s p a r t o f a hem ith io -

a c e ta l group. When i t i s lo c a te d a t p o s i t io n s o th e r th an C -l i t

becomes a p rim ary , o r secondary t h i o l . One ro u te from a secondary

a lco h o l group in a su g ar r in g to th e corresponding secondary th io l

I s by p y ro ly s is of a x an th a te e s t e r : R-o(C=S)S2t-* R-S(C=0)SEt, bu t

th e re a c t io n g iv es low y ie ld s and I s no t o f g e n e ra l u t i l i t y . I t

was proposed to exp lo re th e p h o to ly s is o f compounds of t h i s ty p e , in

p a r t i c u la r th e r e l a te d d im othylth iocarbam ates^ - R-0 (C=S)NMe2 - t o

( l ) D, Horton and H. S . P r ih a r , Carbohyd. R e s ., 115 (1967).

1

determ ine whether such a rearrangem ent could be e f fe c te d p h o to ly t-

i c a l l y . I t i s known th a t C-S bonds in carbohydrate d e r iv a tiv e s can

be c leaved by l i g h t and a p o s s ib i l i ty e x is te d th a t th e p h o to ly s is

might a l t e r n a t iv e ly g ive r i s e to a deoxy sugar (RH), i t s e l f a u se fu l

s y n th e tic o b je c tiv e in carbohydrate chem istry .

HISTORICAL

pThe c la s s ic a l work on th io sugars was reviewed by Raymond

(2) A. L. Raymond, Advan. Carbohyd. Chem., 1 , 129 (1945).

3in 1945. More re c e n t review s have been made by Reid and by Horton

(3 ) E. E. R eid, "Organic Chemistry of B iv a len t S u lfu r ,"

Chemical P ub lish ing C o., I n c . , New York, N. Y ., 1958, Vol. I , pp.

391-394; I 9 60 , Vol. I I , pp . 221- 222 ; i 9 60 , Vol. I l l , pp. 349-361.

and H utson .^ G eneral p re p a ra tiv e methods fo r 1 - th io su g a rs , and

(4 ) D. Horton and D. H. Hutson, Advan. Carbohyd. Chem., 18 t

123 (1963).

5t h o i r l -S -a lk y l and a ry l d e r iv a tiv e s aB w ell as a review o f th e

(5) D. H orton, Methods Carbohyd. Chem., 2 , 433 (1963) .

1 - th io g ly c o s id e s^ were d esc rib ed by Horton.

(6) D. H orton, i b id . f 2 , 368 (1963).

3

A. N a tu ra lly occu rring 1 - th io - D -glucosides

The most common source of n a tu r a l ly occu rring g ly co sid es of

1 -th io -D -g lu co se i s found in th e m u sta rd -o il g lu co s id es of the

C ru c ife ra e r Cap p arid aceae . and Hesodaceae p la n t f a m ilie s .^ - This2 7 * 8—10su b je c t has been review ed by Raymond, Z inner, K ja e r , and

(7) G. Z inner, Deut. A po theker-Z tg ., 335 (1958).

(8 ) A. K ja e r , in "Organic S u lfu r Compounds," N. K harasch,

e d . , Pergamon P re s s , London, 1961, Vol. I . , p . 409.

(9) A. K ja e r , F o rtsc h r , Chem. Org. N a tu rs to ffe , 18, 122

(I960).

(10) A. K ja e r , in "Handbuch der P flan zen p h y sio lo g ie ,"

W. Ruhland, e d . , S p ringer V erlag , B e r l in , 1958, Vol. 9 , p . 71.

Horton and H utson,^ The f i r s t example of t h i s s e r ie s was i s o la te d in

1831 by Robiquet and B o u tro n ,^ The most tho rough ly s tu d ie d example

(11) R. J . Robiquet and F . Boutron, J . Pharm ., 17, 279 (1831)

o f t h i s group has been s in ig r in . This compound was i s o la te d in 1839

from seeds o f b lack m ustard , B ra ss lc a n ig ra Koch. S tru c tu re ( i ) fo r12s in ig r in , proposed by Gadamer, was accep ted f o r many y e a rs . The

(12) J . Gadamer, Arch. Pharm ., 235, 44 (1897).

s t ru c tu r e assignm ent was based on th e enzymic h y d ro ly s is of s in ig r in

to a l l y l iso th io c y a n a te , _D-glucose, and hydrogen s u l f a te io n . The

5

S tru c tu re I

s t ru c tu re was supported by th e cleavage of s in ig r in w ith s i lv e r13n i t r a t e to give D-glucose and s i l v e r s in ig r a te and by trea tm en t o f

(13) W. S chneider, H. F is c h e r , and W. Specht, B e r ., 63.

2787 (1930).

s in ig r in w ith sodium m eth o x id e^ to o b ta in 1 - th io -D -g lu co se . E t t l in g e r

(l/O W. Schneider and F. Wrede, i b id . , LI. 2225 (1 9 H ) .

and lu n d e e n ^ p o in ted out t h a t s t ru c tu re ( I ) c o n tra d ic te d th e f a c t

(15) M. G. E tt l in g e r 'a n d A. J . Lundeen, J . Amer. Chem. S o c .,

2 8 , 4172 (1956).

th a t s in ig r in y ie ld e d a n i t r i l e and carb o x y lic a c id having th e same

number o f carbon atoms as th e enzym ically formed iso th io c y n a te , and

no t th e amine expected from ( I ) . When s in ig r in was reduced w ith

Raney n ic k e l , n-butylam ine was formed and i s o la te d in y ie ld as

th e £ -n itrobenzam ide . Acid h y d ro ly s is of s in ig r in gave v in y la c e tic

^ ( fo r s i n ig r in , R=CH sCH-CHg-)

S tru c tu re ( I I )

The enzymic breakdown of th e m u sta rd -o il D -glucosides to is o -

th io c y a n a te s can be d esc rib ed as an i n i t i a l lo s s o f th e g lycosy l

m oiety fo llow ed by a 1 , 2 - in tra m o le c u la r s h i f t .

a c id and hydroxylam ine. E t t l in g e r and Lundeen^-5 proposed s t ru c tu re ( I I )

f o r th e m u sta rd -o il D -g lucosides.

HC

R-N=C=S+

HSO. “ 4

7

E tt l in g e r and Lundeen l a t e r v e r i f i e d th e newly proposed

(16) M. G. E t t l in g e r and A. J . Lundeen, i b id . . 79T 1764

(1957).

s t r u c tu r e by sy n th e s iz in g g lu c o tro p a e o lin ( s t r u c tu r e I I , R=C£|H ch2- ) .17Waser and Watson confirm ed th e proposed s t ru c tu r e fo r s in ig r in

(17) J . Waser and W. H. Watson, N a tu re , 198T 1297 (1963).

( s t r u c tu r e I I , R^CP^CH-CI^-) by X -ray c ry s ta l lo g ra p h ic a n a ly s is , and

e s ta b l is h e d th e svn d is p o s i t io n between th e s u l f a te group and th e 1 -

th io -D -g lu co se m oiety about th e C=N double bond. The f i r s t sy n th e s is

o f th e c la s s ic a l exam ple, s i n i g r in , was accom plished by Benn and

E t t l i n g e r B e n n -*-9*20 r e p o r te d a new sy n th e s is of m u s ta rd -o il

(18) M. H. Benn and M. G. E t t l in g e r , Chem. Commun., 445

(1965).

(19) M. H. Benn, Can. J . Chem., 41j 1 (1965).

(20) M. H. Benn, i b i d . , £L, 2836 (1963).

D -glucosides and th e m ajor r e a c t io n sequence i s g iven on th e fo llow ing

page fo r g lu c o a u b r ie t in . Benn and co-w orkers have sy n th e s ize d g lu co -

s in a lb in 19 ( I I , R ^-H O C ^C H g), g lu c o a u b r ie tin ( I I , R ^ p -C ^ O C ^ C I^ ) ,

g lu c o tro p a e o lin 20 ( I I , R=PhCH2 ) , g lucoapparin 21 ( I I , R=CH3) , g lu co -

n a s tu r i in 22 ( I I , R=PhCH2CH2 >, g lu c o p u tra n jiv in 23 [ I I j .R ^ C I ^ C I I ] , g luco-p/

c o c h le a r in [ I I , R=(CH3CH2 )(CH3 )CH] as potassium or tetramethylammoniura

s a l t s by t h i s method.

R C l

E tpRO-

/ , vx NOH ^ ^ - C H C C l S ^

E tpH O N - d "

2.

R = CKCHOAc >SH

AcO

R O \ _ / C H â r s r ^ T )C=N0S0'X+ AcOCHj s

■O

AcO

i)py-S03AcO CH , S/C ^QH

OAc

2) KHCG3 AcOOAc OAc

Structure n ( R=0H3O-v^ / CHz) Glucoaubrietin

9

(21) M. H. Benn, ib id . T £2 , 163 (1964).

(22) M. H. Benn, J . Chem. S o c ., 4072 (1964).

(23) M. E. Benn and D. Meakin, Can. J . Chem., 42» 1874

(1965).

(24) M. H. Benn and L. Y elland , i b id . t 4 5 . 1595 (1967).

The s im i la r i ty of sev o ra l s id e -c h a in s of th e m u sta rd -o il

D -glucosides to those of amino a c id s in p ro te in s suggests a common

pathway in b io g e n e s is .9 ,15 ,23 ,25 ^gee fa b le 1) .

(25) A. K jae r, Acta Chem. S can d ., 8 , 1110 (1954).

O ther m u s ta rd -o il D -glucosides have no obvious re la t io n s h ip

to known amino ac id s (see Table 2 ) , suggesting e i th e r th a t th ey were

formed by a d i f f e r e n t b io sy n th e tic pathway, or th a t a-am ino ac ids23e x is t in Nature th a t have not been recogn ized as y e t . Recent work-

ers*^"29 have lin k e d c e r ta in a-am ino a c id s as b io g e n e tic p rec u rso rs

(26) M. H. Benn, Chem. In d . (London), 1907 (1962).

(27) H. K in d i, Monatsh. Chem., 26 , 527 (1965).

(28) E. W. U n d erh ill and M. D. Chisholm, Biocheiu. Biophys.

Res. Coramun., 1 4 , 425 (1964) .

(29) E. W. U n d e rh ill , M. D. Chisholm, L. R. W etter, Can.

J . Biochem. P h y s io l . , 42 , 1505 (1962).

TABLE 1

GROUPS COMMON TO AMINO ACIDS AND MUSTARD-OIL D-GLUCOSIDES

R* Amino a c id M u sta rd -o il D -glucosides

< W H2 phen y la lan in e g lu c o tro p a e o lin '

e - h o - c ^ c h 2 ty ro s in e g lu c o s in a lb in

CH3 a la n in e g lucoapparin

CH^C^CHCCH^) iso le u c in e g lu co co ch lea rin

(CH3) 2CH v a lin e g lu e o p u tra n jiv in

R i s th e group common to amino a c id s of th e g en e ra l

s t r u c tu r e , R-CHtNH^CO^H, and to th e m u sta rd -o il 1 -th io -D -

g lu c o s id e s , s t ru c tu r e I I .

TABLE 2

GROUPS FOUND ON MUSTARD-OIL D-GLUCOSIDES

NOT COMMON TO AMINO ACIDS

R* M ustard -o il D -glucoside

ch3s (c h 2) 5 g lu c o b e rte rio n

ch3 so(ch2 ) 5 g lu c o a ly ss in

CH SO(CH )3 2 8

g lu c o h irsu tin

c h s o (c h )3 2 9

g lu co arab in

#See s t ru c tu r e I I fo r m u s ta rd -o il D-gluco

s id e s w ith s u b s t i tu e n t R.

12

I t hag been suggested^ th a t th e D -glucosyl s u b s ti tu e n t e x is ts

as a removable b lock ing group fo r b io lo g ic a l s t a b i l i z a t i o n o f re a c

t iv e th io l d e r iv a t iv e s . The D -glucosyl group can be enzym ically

c leaved when th e t h i o l d e r iv a tiv e i s req u ire d in a b io lo g ic a l system .

Most 1 - th io sugar d e r iv a tiv e s do not commonly r e a c t by

cleavage between th e aglycon and th e s u lfu r atom^ (bond b , s t ru c tu re

I I I ) . S c is s io n u s u a l ly occurs between th e sugar and th e s u lfu r atom

Sugar— S — R

S tru c tu re I I I

(bond a , s t r u c tu r e I I I ) . Chemical cleavage of m u s ta rd -o il th io g lu c o -

s id e s as f i r s t shown by S c h n e id e r^ i s an example of th e former

(cleavage a t bond b) to y ie ld l- th io -D -g lu c o s e . Many 1 - th io sugars

have been sy n th e s ize d in th e la b o ra to ry ; however, a review o f the

e n t i r e f i e l d o f th io sugars i s beyond th e scope o f th is d i s s e r ta t io n .

Examples o f th io sugars having th e s u l f u r atom a t p o s it io n s

in th e sugar m olecule o th er th an C-l have been syn thesized^- but have

no t y e t been dem onstrated to occur n a tu r a l ly , w ith th e s o le excep tion

o f 5 - th io -D -r ib o se , which i s a component fragm ent of nS-adenosyl-

m ethionine" th e f a c to r invo lved in methyl g ro u p - tra n s fe r in b io lo g ic a l

r e a c t io n s .

NHZ

H N HqCCCHCH.

NH

OH OH

" S-Adenosylmethionine”

B. S ynthesis o f a c e ty la te d 1 -th io g ly c o - s id e s and a c e ty la te d 1- th io sugars

30The f i r s t recorded p re p a ra tio n of a 1 -th io g ly c o s id e was

(30) E. F isch er and K. Delbruck, B e r ., 4 2 , 1476 (1909).

th a t of phenyl 1 -th io -p -D -g lucopyranoside ob tained by condensation

of te tra -O -ace ty l-c -D -g lu co p y ran o sy l bromide w ith the sodium s a l t

of b e n z e n e th io l, a re a c tio n th a t involved concom itant d e a c e ty la tio n .

This re a c t io n o f a po ly -O -ace ty lg ly co sy l h a lid e w ith a s a l t o f a

t h io l has become a genera l method fo r th e p re p a ra tio n of 1- th io -

g ly co s id e s . Various workers have used th i s method or s l ig h t m odifi

ca tio n s th e re o f to p ropare 1 -th io -p -D -g lucopyranosides ^1*33,34-37*39

1 -th io -p -D -g a lac to p y ran o sid o s ,^ 2 1 -th io -p -D -xy lopy ranosides^8 and

1 -th io -a -L -a rab in o p y ran o s id e s ,^ 0 The condensation of potassium

u

AcOCH. AcOCH

KSAc

AcOOAc

(31) C. B. Purves, J . Amer. Chem. S o c ., 2 i , 3619 (1929).

(32) B. H e lfe r ic h and 0 . Turk, B e r ., 82, 2215 (1956).

(33) W. S chneider, D. C libbens, G. Hiillweck, and W. S t e ib e l t ,

i M i . , 61, 1258 (1914).

(34) W. T. H askins, R. M. Hann, and C. S. Hudson, J . Amer.

Chem. S o c ., 62., 1668 (1947).

(35) E, M. Montgomery, N. K. Richtm yer, and C. S . Hudson,

J . Org. Chem., 11 , 301 (1946).

(36) J . S tanek , K. Malkovsky, M. Nov&, and D. P e tr ic e k ,

C o lle c t. Czech. Chem. Commun., 22, 336 (1958).

(37) W. S chneider, J . Sepp, and 0 . S t ie h le r , B e r . , 51,

220 (1917).

(38) H. Z inner, A. Koine, and H. Nimz, i b i d . , 22 , 2705

(I9 6 0 ).

(39) C. V, H olland, D. H orton, M. J . M il le r , and N. S.

Bhacca, J . Org. Chem., 22 , 3077 (1967).

15

(4-0) B. Coxon, P . M. C o ll in s , A. A. Levy, and W. G.

Overend, J . Chen. S o c ., 3242 (1964).

th io la c e ta te w ith tri-O -ace ty l-c trD -x y lo p y ran o sy l bromide gave 1 - th io -

(41) M. Gehrke and W. K oh le r, B e r . , 6 4 , 2696 (1931)*

(42) D. Horton and M. L. Wolfrom, J . Org. Chem., 27,

1794 (1962) .

(43) F. D a n ie l l i , M. D a n ie l l i , J . B. F ra se r , P . D.

M itc h e ll , L. N. Owen, and G. Shaw, Biochem. J . , 325 (1947).

39and 1 -th io -p -D -g a lac to p y ran o se p e n ta a c e ta te . The ste reochem ica l

outcome a t C -l in th e se condensations i s not th e r e s u l t of an SN2

type o f re a c t io n bu t i s governed by th e form ation o f an in te rm e d ia te ,

c y c l ic , 1 , 2 -acetoxonium ion which i s opened s te r e o s p e c i f ic a l ly by

th e th io la c e ta te n u c le o p h ile .

p-D-xylopyranose t e t r a a c e t a t e . T h e method was extended fo rZ.2 13th e p re p a ra tio n o f 1 -th io -p -D -g lucopyranose p e n ta a c e ta te , *

I©SAcAcOCH AcOCH AcOCH

In o rd er to o b ta in the a-D anomer i t i s n ecessa ry to e f f e c t

a condensation in a system wherein th e C-2 s u b s t i tu e n t i s a le s s

e f f e c t iv e p a r t i c ip a t in g group, and w ith th e p ro p er o r ie n ta t io n of

th e h a lid e group so th a t an SN2 type o f d isplacem ent can be e f fe c te d .

A ccordingly , Tejima and c o -w o rk e rs ^ condensed potassium

(44) M* S ak a ta , M. Haga, S. Tejim a, and M, Akagi, Chem.

Pharm. B u ll. (Tokyo), 12, 652 (1964-).

th io la c e ta te w ith 3 ,A ,6 - tr i-0 -a c e ty l-p -D -g lu c o p y ra n o sy l ch lo rid e w ith

subsequent a c e ty la t io n to g ive 1 - t h i o —a-D -glucopyranose p e n ta a c e ta te .

AcOCH.

AcO

OAcAcOCH AcOCH.

PCI,

AcOOAc

KSAc

AcOCH

AcO

AcOCHz

NaOAc

S A c ^ ° " AcOQA:

SAc

17

Schneider and E i s f e l d ^ re f lu x e d te tra -O -a c e ty l-a -D -g lu c o -

(4-5) W. Schneider and K. E is f e ld , B e r . , 61, 1260 (1928).

pyranosy l bromide in d ry to lu e n e u i th th io u re a to o b ta in a product

in moderate y ie ld d e sig n a ted as 2 - (2 ,3 ,4 ,6 - te tra -O -a c e ty l-p -D -

g lu co p y ran o sy l)-2 -th io p seu d o u rea hydrobrom ide. They observed a

AcOpH* AcOCH, NHHBr

(NHJC=S

AcOOA: OA:

SCNH

s im ila r condensation re a c tio n when p h en y lth io u rea was used in s te a d

o f th io u re a . Bonner and K ah n ^ m odified th e method by s u b s t i tu t in g

(46) W. A. Bonner and J . E. Kahn, J . Amer. Chem. S o c ., 73,

2241 (1951).

iso p ro p y l a lco h o l fo r to lu e n e as th e re a c tio n s o lv e n t, and in c reased

th e y ie ld of th e 2 -g lu co sy l-2 -th io p seu d o u re a hydrobromide to 64$ .

T h e y ^ extended th e method to th e p re p a ra tio n of 2 - (2 ,3 ,4 ,6 - to t r a -0 -

ace ty l-p -D -g a la c to p y ran o sy l)-2 -th io p se u d o u re a hydrobrom ide, 2 -(2 ,3 ,4 -

tr i-O -a ce ty l-p -D -x y lo p y ra n o sy l)-2 -th io p se u d o u re a hydrobrom ide, and

to a p o ly a c e ty la te d c e l lo b io s y l pseudourea hydrobrom ide.

18

Corny, Vrkoc, and S ta n e k ^ fu r th e r improved th e y ie ld of th e

(47) M. Cerny, J . Vrkoc, and J . S tanek , C o lle c t . Czech.

Chem. Commun., 24, 64 (1959)*

2 -g lu c o sy l-2 -th io p seu d o u rea hydrohalide by s u b s t i tu t in g acetone f o rfrj

iso p ro p y l a lc o h o l as th e r e a c t io n s o lv e n t. These workers p repared

2 - ( 2 , 3 ,4 ,6- te tra -O -a c e ty l-p -B -g lu c o p y ra n o sy l)-2 -th iopseudourea hydro

gen ca rb o n a te , a compound p re v io u s ly d escrib ed by Schneider and 45E is fe ld , by adding a s o lu t io n o f sodium hydrogen carbonate to an

aqueous s o lu tio n of th e g lu co sy l th iopseudourea hydrobrom ide. The

2 -g lu c o s y l-2 -th io p seu d o u rea hydrogen carbonate was th en decomposed

to 2 ,3 ,4 ,6 - te tra -O -a c e ty l- l- th io -p -D -g lu c o p y ra n o se by h e a tin g w ith

sodium hydrogen s u l f i t e in e th y l a c e ta te . The l-th io -D -g lu co p y ran o se

AcOCH WKHC°3scnh2

AcO

AcOCH

NaHSO,

AcOOAc OAc

d e r iv a tiv e was a ls o o b ta in ed when an aqueous s o lu tio n of th e th io -

pseudourea hydrobromide was combined w ith a s a tu ra te d aqueous s o lu t io n

o f sodium hydrogen s u l f i t e . The p re lim in a ry in v e s t ig a t io n le d to a

g e n e ra l procedure f o r th e p re p a ra tio n o f p e r-O -a c e ty la te d g lycosy l

19

t h i o l s . The l a t t e r could be S -a c e ty la te d to g ive p e ra c e ty la te d

1 - th io a ld o p y ra n o s e s .^ ”^ The method c o n s is te d of d isso lv in g an

(48) J . S tanSk, M. § in d le ro v a , and M. Cerny, i b i d . , ^0 ,

297 (1965).

(49) M. fe rn y , J . StanSk, and J . Pacak, Monatsh. Chem.,

24 , 290 (1963).

AcOCHz NH-HBr AcOpHz S C N h ^

_NaHSQ

AcO

Water AcO / OrganicSoluble 1 J Soluble

AcOCH2■Q

a c e ty la te d g ly co sy lth io p seu d o u rea hydrohalide in aqueous sodium

hydrogen s u l f i t e . . The O -ace ty la ted 1 - th io sugar formed was immedi

a te ly p a r t i t io n e d by way of an heterogeneous so lv e n t system between

w ater and e i th e r carbon te t r a c h lo r id e o r chloroform . This method

20

was u s e d ^ fo llow ed by a c e ty la t io n o f th e 1 - th io sugar to p repare

1-th io -p -D -g lucopyranose p e n ta a c e ta te and 1- th io -a -D -a ra b in o -

pyrano3e t e t r a a c e ta te from t h e i r corresponding 2 -g ly c o sy l-2 ~ th io -

p-D -ribopyranose t e t r a a c e ta te and 1 - th io -a -L -a rab in o p y ran o se

t e t r a a c e ta t e from th e i r corresponding th iopseudourea hydrobromides

the g e n e ra l i ty o f th e method to inc lude th e p re p a ra tio n o f 2 , 3 , 4 - t r i -

Q -ace ty l-l- th io -p -D -x y lo p y ran o se and 2 ,3 , 4 ,6- t e t r a - 0 - a c e ty l - l - t h lo -

p -p -g a lac to p y ran o se .

A p rev ious p re p a ra tiv e ro u te fo r te t r a -O -a c e ty l- l - th io -p -D -

glucopyranose had been by red u c tiv e cleavage o f b is(p-D -g lucopyranosy l)

d is u l f id e o c ta a c e ta te .^ ^ » ^ » ^

pseudourea hydrobrom ides. Horton and co-workers-3 p rep a red 1 - th io

by an a d a p ta tio n o f t h i s method. Cerny and c o -w o rk e rs^ extended

(50) W. Schneider and A. Bansa, B e r . , 64 , 1321 (1931).

(51) F . Wrede, Z. P h y s io l. Chem., 119, 46 (1922).

AcOC H2 5 S

EtOH, 50% HQAc , Al-Hg

AcOCH

AcOCH,L - O

\O A c

CAc

AcOCAc

21

The 1 -th io -p -D -g lucopyranose p e n ta a c e ta te was ob ta in ed by

a c e ty la t io n o f th e 1 - th io group. Another ro u te was by c leavage of

te tra -O -a c e ty l-p -D -g lu c o p y ran o sy l e th y lx a n th a te w ith m ethanolic52ammonia fo llow ed by a c e ty l a t i o n . '

(52) W. S ch n e id er, R. G i l le , and K. E is f e ld , B e r . , 61,

1244 (1928).

AcOCH AcOCHsfiO EtKSCOEt

-f Br OAc

AcO AcOOAcMeOHNH»

AcOCH AcOCHSAc QSHacetylation

OAc OAcAcO Ac

OAc

22

C. S yn thesis o f l- th io g ly c o s id e s by a c id -c a ta ly z e d g ly c o s id a tio n

The re a c t io n o f an a lc o h o l w ith the aldehyde group of a

sugar in th e presence of an a c id c a ta ly s t to produce a g lycoside

i s a well-known re a c t io n . F is c h e r rep e a te d t h i s procedure

(53) E. F is c h e r , i b i d . , 26, 2400 (1893).

(54) E. F is c h e r , i b id . . 27 , 673 (1894).

CHOH CHOH

MeOHOH OM ePH

HO HOOH OH

w ith various t h io l s in p la c e o f a lc o h o ls , bu t o b ta in ed in s te a d th e

corresponding d i th io a c e ta ls .

CH(SR\HCOH

h o 6 hH<iOHHCOH

OH dHOHX

23

Schneider and S e p p ^ sy n th esized an e th y l 1 -th io -D -g lu co sid e

(55) W. Schneider and J . Sepp, B e r ., £ 2 , 2054 (1916).

by decomposing D-glucose d ie th y l d i th io a c e ta l i n the presence of56 57m ercuric c h lo r id e and b ase . Pacsu and co-w orkers J favored an

(56) J . W. Green and E. Pacsu , J . Amer. Chem. S o c .,

1205 (1937).

(57) E. Pacsu and E. J . W ilson, J r . , i b i d . , 61, 1450 (1939).

a -D -fu ranoside s t r u c tu r e fo r th e e th y l 1 -th io -D -g lu co sid e by o p t ic a l

r o ta r y evidence based on Hudson's ru le s o f r o ta t io n and by ease ofCg

h y d ro ly s is in 0.01N h y d ro ch lo ric a c id . Wolfrom and co-w orkers3

(58) M. L. Wolfrom, S. W. W aisbrot, D. X. W eisb la t, and

A. Thompson, i b id . , 66, 2063 (1944).

su b je c te d th e e th y l 1 -th io -D -g lu co s id e t o p e rio d a te o x id a tio n and

showed th a t 1 mole o f form aldehyde was produced, thus e s ta b l is h in g

th e fu ran o s id e s t r u c tu r e .

Under ex tended tim es o f re a c tio n and a t h igher tem p era tu re s ,

th e a c id -c a ta ly z e d m erc ap ta la tio n re a c tio n s o f sugars may g ive

l- th io g ly c o s id e s in moderate y ie ld s . F rie d and Walz^9 were ab le to

(59) J . F rie d and D. E. Walz, i b id . . 71 , 140 (1949).

24

o b ta in a m oderate y ie ld o f e th y l l-th io -p -J^m annopyranoside ( is o -

l a t e d as th e t e t r a a c e ta te ) when m ethyl o - o r p-D-mannopyranoside

was e q u i l ib ra te d f o r 18 hours w ith e th a n e th io l and hydroch lo ric

a c id a t room tem p era tu re . A sm all p ro p o rtio n o f th e a-D anomer

was o b ta in ed in th e re a c t io n w ith m ethyl p-D-mannopyranoside. A

s l i g h t l y b e t t e r y i e ld was ob ta ined when th e f r e e sugar was used.

Wolfrom, H orton, and Garg^® ob ta ined a 31% y ie ld o f e th y l

(60) M. L . Wolfrom, D, H orton, and H. G. Garg, J . Org.

Chem., 28 , 1569 (1963).

1 - th io - a - and p-D-mannopyranosides ( i s o la te d as th e t e t r a a c e ta te s )

upon p ro longed trea tm en t o f D-mannose w ith e th a n e th io l and concen

t r a t e d (12N) h y d ro ch lo ric a c id a t room tem p era tu re . They were ab le

t o show by paper chrom atographic evidence th a t a f t e r 5 m inutes a l l

o f th e mannose had re a c te d and th e m ajor p roduct was th e d ie th y l

d i th io a c e ta l accompanied by minor p ro p o rtio n s o f th e two th io g ly c o -

s id e s . At longer r e a c t io n tim es th e zones corresponding to th e

CHO CKSEt) CHOHOCH HOCH CHpH Ho 6 - iHOCH HOCH / - O HOCH

H(?OH ~TT+—*“ h ?OH / OHHpV s E t ♦ HCOHHCOH H HCOH h 6 \L _ Y HCOH

CHpH CHpH CH2OH

l - th io g ly c o s id e s in c reased in in te n s i ty w hile th e in te n s i ty o f the

d i th io a c e ta l zone decreased and an a d d it io n a l zone appeared c o r re s

ponding to D-mannose.~ 61,62

The re a c tio n of th e d ie th y l d i th io a c e ta ls o f D-glucose

(61) E. Pacsu and E. J . W ilson, J r . , J . Amer. Chem. S o c .,

61, 1930 (1939).

(62) P. B r ig l , K. Gronemeier, and A. S chu lz , B e r ., 72,

1052 (1939).

and D -g a la c to s e ^ w ith a m ineral a c id gave low y ie ld s of 1 -th io -D -

g lycopyranosides. As a p re p a ra tiv e ro u te fo r 1 -tb io a ld o p y ran o sid es

th e aldose d ia lk y l d i th io a c e ta ls have not proven to he s a t i s f a c to r y

p re c u rso rs fo r a g e n e ra l, h ig h -y ie ld in g method.

B r ig l and S c h in le ^ t r e a te d p-D -glucopyranose pentabenzoate

(63) P. B r ig l and R. S c h in le , i b id . . 6£, 1890 (1932).

w ith e th a n e th io l in th e presence o f h yd roch lo ric a c id , but ob ta in ed

a complex m ixture o f p ro d u c ts . Wolfrom and Thompson * m odified

(64) M. L. Wolfrom and A. Thompson, J . Amer. Chem. S o c .,

56 , 880 (1934).

(65) M. L. Wolfrom and A. Thompson, i b i d . , 5 6 , 1804 (1934).

B r ig l and S ch in le*s co n d itio n s by th e use o f z in c c h lo rid e a s th e

c a ta ly s t in th e p resence o f a d ry ing agent to minimize acid

h y d ro ly s is of a c e ty l groups in th e m ercap to ly sis of p -p -fru c to se

p e n ta a c e ta te . They showed th a t p -D -fruc tose p e n ta a c e ta te undergoes

m ercap to ly sis in th e presence of e th a n e th io l to form e th y l 2 - th io -

in c lu d e th e use o f o - and p-D-glucopyranose p e n ta a c e ta te and -D-

ga lactopyranose p e n ta a c e ta te to form t h e i r corresponding e th y l 1 - th io -

g ly co s id e t e t r a a c e ta t e s . He ob ta in ed a 71.2$ y ie ld o f e th y l 1 - th io -

p-D -glucopyranoside te t r a a c e ta te and a 75 .6% y ie ld o f e th y l 1 - th io -p -

D -galactopyranoside t e t r a a c e ta te from th e i r re s p e c tiv e p-D -aldopyranose

p e n ta a c e ta te s , bu t found m ercap to ly sis of th e a -p e n ta a c e ta te s was not

a p ra c t ic a b le method fo r sy n th e s is of l - th io g ly c o s id e s . The re a c tio n

was d e s c r ib e d ^ as a b s tra c tio n of th e O -acety l group a t C -l i i i th

p -D -fru c to s id e t e t r a a c e ta t e , L em ieux^ extended th e procedure to

(66) R. U. Lemieux, Can, J . Chem., 2£, 1079 (1951).

(67) R. U. Lemieux, M van. Carbohyd. Chem., 2 , 1 (1954).

AcOCH* £n O AcOCH* K- AcOCH

O-CCH©

27

synchronous a tta c k of th e 2 -a c e ty l group to form th e c y c lic carbonium

ion follow ed by a tta c k of th e s u lfu r atom of e th a n e th io l t o g ive th e

e th y l 1 -th io -p -D -g ly co sid e t e t r a a c e t a t e .

The re a c tio n method has been extended to fo rm ation of e th y l

tetra-0-acetyl-l-thio-a-D-mannopyranoside.^>^ F le tc h e r and co-70workers have dem onstrated th e a p p l i c a b i l i ty of th e method fo r

(68) R. U. Lemieux and C, B r ic e , Can. J . Chem.,21 , 109

(1955).

(69) F. Weygand and H. Ziemann, Ann., 657. 179 (1962).

(70) H. B. Wood, J r . , B. Coxon, H. W. D ie h l, and H. G.

F le tc h e r , J r . , J . Org. Chem., 22, 461 (1961).

p re p a ra tio n of t e r t -b u tv l 1 -th io -p -D -g lu co p y ran o sid e t e t r a a c e ta te

from p-D -glucopyranose p e n ta a c e ta te .

D. Form ation and r e a c t i v i ty o f t e t r a - 0 - ace ty l-p -D -g lu c o p y ran o sy lsu lfen y l bromide ~

A s u lfe n y l compound may be defined*^ as a compound th a t

(71) N. K harasch, in "Organic S u lfu r Compounds," Vol. 1 ,

K harasch, e d . , Pergamon P re s s , New York, 1961, pp . 375-396.

(72) 0 . F oss, Acta Chem. S cand ., 1 , 307 (1947).

(73) R. H. B e ll , M.S. t h e s i s , The Ohio S ta te U n iv e rs ity ,

1967.

28

can undergo re a c tio n s ty p ic a l of th e p o la r iz a t io n R ^+ — X^- and th e

compound where X i s a h a lid e io n i s known as a su lfe n y l h a lid e .7 AA ry lsu lfen y l c h lo r id e s have been known fo r over 50 y e a r s '^ and

75m ethanesu lfenyl c h lo r id e was d esc rib ed by Rathke,J in 1870.

(74-) T. Z incke, B e r . , 769 (1911).

(75) B. R athke, i b id . . 2 , 858 (1870).

The f i r s t carbohydrate su lfe n y l h a lid e was rep o rte d by H orton, 76

Wolfrom, and Garg. They brom inated a carbon te t r a c h lo r id e so lu tio n

(76) D. H orton, M. L . Wolfrom, and H. G. Garg, J . Org.

Chem., 28, 2992 (1963).

o f 1 -th io -p-D -glucopyranose p e n ta a c e ta te and were ab le to o b ta in

te tra -O -a c e ty l-p -D -g lu c o p y ran o sy lsu lfe n y l bromide in h igh y ie ld .76These workers exp la ined th e form ation o f th e s u lfe n y l bromide as

shown below.

BrAcOCH, f AcOCH, I

* S~Ac T _ i S-AcQ / —Ov I©

AcO

AcOCH

AcOOAc

SB r

29

The r e a c t io n proceeds w ith i n i t i a l h a lo g en atio n o f s u lfu r

fo llow ed by h e te ro ly s is o f th e s u lfu r to a c e ty l bond (bond a) to

g ive corresponding g lu c o sy lsu lfe n y l bromide and acetylium io n ,

which combines w ith th e h a lid e to form a c e ty l brom ide. H e te ro ly s is

o f th e C -l to S bond (bond b ) , and subsequent a tta c k o f th e bromide

ion a t C -l would have formed te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l

brom ide. Bonner*^ d escrib ed th e l a t t e r type o f re a c t io n in th e

(77) W. A. Bonner, J . Amer, Chem. S o c ., 70, 3491 (1948)

broraination of phenyl te tra -O -a c e ty l- l- th io -p -D -g lu c o p y ra n o s id e .

D p —-

AcOCH, AcOCH* , | Br AcOCH,*SPh }— 0

OAc OAc + OAcPhSBr

78 73Horton and M il le r ' and B e ll ^ dem onstrated th e g en e ra l

(78) D. Horton and M. J . M il le r , Carbohyd. R e s ., 1 , 335

(1965).

r e a c t i v i ty o f te tra -O -a c e ty l-p -D -g lu c o p y ra n o sy lsu lfe n y l bromide by

form ing adducts w ith b e n z e n e th io l, a - to lu e n e th io l , £ -c h lo ro a n il in e ,

30

and cyciohexene. The y ie ld o f g lu c o sy lsu lfe n y l bromide was alm ost

q u a n t i ta t iv e when a sm all p o r tio n (0 .5 g) o f 1 -th io -p -D -g lucopyranose

AcOCH* S-NhHy^) A c0^ o S - S Q

/ ^ ci / ~ ° \ l

AcO

OAc

AcOOAc

AcOPhSH

AcO C 'A - o S B r

OAc

AcOCH*• o s

PhCH SHZ

A c O C H i

OAc

76p e n ta a c e ta te was b ro rainated , b u t th e y ie ld and p u r i ty o f the p roduct

were e r r a t i c w ith la rg e r b rom ination re a c t io n s . I t was d e m o n s tra te d ^

th a t th e g lu c o sy lsu lfe n y l bromide cou ld be o b ta in ed in la rg e amounts

( ~ 2 0 g) i f th e carbon te t r a c h lo r id e suspension of 1 -th io -p -D -g lu co -

pyranose p e n ta a c e ta te were coo led to about -15° b efo re b rom ination .

E. Photochem istry of carbohydrates

Chemists have been concerned w ith th e photochem istry of

carbohydrate d e r iv a tiv e s fo r many y e a r s . A d e ta i le d review of

th e e a r ly work, m ainly on d eg rada tions o f th e f r e e su g a rs , t h e i r79a l d i t o l s , and g ly c o s id e s , i s g iven by G. 0 . P h i l l ip s and i s

no t e la b o ra te d upon in t h i s d i s s e r t a t io n .

(79) G. 0 . P h i l l i p s , Advan. Carbohyd. Chem., 18, 9 (1963).

80Noyes, P o r te r , and J o l l e y , have d e fin ed a prim ary

(80) W. A. Noyes, J r . , G. P o r te r , and J . G. J o l l e y ,

Chem. R ev ., £6 , 49 (1956).

photochem ical p ro cess as " th e s e r ie s o f even ts beginning w ith th e

a b so rp tio n of a photon by a m olecule and ending e i th e r w ith th e

d isappearance o f th a t m olecule o r w ith i t s conversion to a s t a te

such th a t i t s r e a c t i v i ty i s s t a t i s t i c a l l y no g re a te r th an th a t o f

s im ila r m olecules In therm al e q u ilib riu m w ith t h e i r su rro u n d in g s."

The energy va lues fo r s in g le bonds occu rrin g most f re q u e n tly81in carbohydrate compounds a re g iven in Table 3 .

(81) L. P a u lin g , "The N ature o f th e Chemical Bond," C o rn e ll

U n iv e rs ity P re s s , I th a c a , N. Y ., I960 , p . 85.

32

TABLE 3

ENERGY VALUES FOR SINGLE BONDS

Bond Bond energy (Kcal/m ole)

C-C 83.1

C-H 98.8

C-N 69.7

C-0 84.0

c -s 62.0

C-I 57.4

82P h i l l ip s and B arber i r r a d i a t e d aqueous so lu tio n s o f D -g luc i-

(82) G. 0 . P h i l l ip s and P . B a rb e r , J . Chem. S o c ., 3990

(1963).

t o l fo r extended p e rio d s of tim e and ob ta ined v a rio u s deg radation

p ro d u c ts . They showed th a t l i g h t from a m edium -pressure mercury a rc

lamp o f 2300-2537A., co rrespond ing to 124-113 k cal/m o le was s u f f ic ie n t

to cause d eg rad a tio n o f D -g lu c i to l. L igh t in t h i s wavelength range

i s s u f f i c i e n t to ru p tu re any bond l i s t e d in Table 3 .

Recent photochem ical re a c t io n s w ith carbohydrates have been

undertaken from e i th e r a m ech an istic o r p re p a ra tiv e approach. Horton 81

and Turner * r e p o r te d th e fo rm ation o f 6 -S -ace ty l-5 -deoxy-l,2 -£L -

(83) D. Horton and W. N. T urner, Ghem. In d . (London), 76

(1964); Carbohyd. R e s ., 1 , IM (1966).

33

is r ip rn p v lid en e -6 -th io -c -D -x v lo -hexofuranose by th e pho toca ta lyzed

a d d itio n o f t h io l a c t i c a c id to 5 ,6 “d id eo x y -l,2 -0 -iso p ro p y lid e n e -

c-D-x v lo -hex-5-enofurano3e. The re a c tio n proceeded w ith n e t a n t i -

Markownikoff a d d it io n , presum ably by a f r e e - r a d ic a l mechanism.

CH* qi^SAcn *CH (X

MeCOSH ,OH

CMe.

P H J \Q hv

8AIn an analogous r e a c t io n , W h is tle r , Wang, and Inokawa ^

(84) R. L . W h is tle r , C. Wang, and S. Inokawa, J . Org.

Chem., 32., 2495 (1968).

d e sc rib ed th e photochem ical a d d it io n o f phosphines to 5 ,6 -d id e o x y -l,2

O -isopropy lidene-q -D -xv lo -hex -5 -enofu ranose to g ive b is (5 ,6 -d id e o x y -

1 .2 -0 -iso p ro n y lid e n e -q -D -x v lo -hexofurano3e-6-v l)phosph ine oxide.

Another m ajor p roduct was p o s tu la te d as th e p rim ary phosphine and

a minor product was th e phosphonous a c id . I t was no t p o s s ib le to

i s o l a t e th e phosphine from th e phosphonous ac id because o f apparen t

a i r o x id a tio n o f th e form er to th e l a t t e r . The phosphonous a c id

was i s o la te d as i t s cyclohexylammonium s a l t .

P h o to ad d itio n o f phenyl phosphine to th e sugar o le f in gave

a good y ie ld o f a secondary phosphine o x id e . I t was p o s tu la te d

34

CHPHL

Q hvXM exCMe.

OH,CMe

^ C M e ,

th a t th e phosphine oxide formed by a i r o x id a tio n o f th e secondary

phosphine.

h/.PhPH2MeOH

CHrP-PhI 2

C 12-g-Ph

35

P h o to ly sis o f a m ethanolic s o lu t io n of D -galactose d ie th y l85d i th io a c o ta l gave a m ixture o f p ro d u c ts . The i n i t i a l product

(85) D. Horton and J . S. J e w e ll , J . Org. Chem,, 21 , 509

(1966).

was 1 - S - e tb y l- l - th io - D - g a la c t i to l , f u r th e r i r r a d ia t io n gave 1-deoxy-

D - g a la c t i to l , 1 -d e o x y - l-e tb y ls u lf in y l-D -g a la c ti to l and a sm all

CH(SEt)z

hv'

HCOH HOCH HOCH MeOH

HCOH C H pH

CHjSEtHCOH

HOCHHOCH

HCOHin OH

CH, HCOH

HOCH + HOCH

HCOH CHOH

9C H jS E t

H(ioH HOCH + HOCH

HCOH C H p H

C H p HHCOH

HOCHHOCH

h £ o h

CHpH

amount o f g a l a c t i t o l . P h o to ly sis o f pure 1 -S -e th y l- l- th io -D -

g a l a c t i t o l in m ethanol gave l-d e o x y -B -g a la c ti to l , 1 -d eo x y -l-

e th y ls u l f in y l- D - g a la c t i to l , and g a l a c t i t o l . P h o to ly sis o f 1-deoxy-

1 - e th y ls u l f in y l -D -g a la c t i to l in m ethanol gave g a l a c t i t o l .

I r r a d ia t io n o f the sodium s a l t o f 2 -d e o x y -2 -(2 ,4 -d in itro -

a n ilin o )-D -g lu c o n ic ac id in e i th e r w ater or aqueous sodium hydrogen86carbonate gave D -arabinose, I r i ’a d ia tio n of an aqueous m ethanolic

36

(86) A. E. El Ashmawy, D. H orton, and K. D. P h i l l ip s ,

Carbohyd. R e s ., % 350 (1969).

m © © NaCC\

H O ? H N O 7 - J O LHCOH i 3 h r HCOH

in p H2

s o lu tio n o f l - d e o x y - l- (2 ,4 -d in i t ro a n i l in o ) -D -g lu c i to l fo r 96 hr

gave no decom position.87B inkley and B inkley photo lyzed a m ethanolic s o lu t io n o f

(87) W. W. B inkley and R. W. B ink ley , i b id . , 8 , 370 (1968).

6 -d eo x y -6 ~ io d o -l,2 ,3 ,A 'd i-0 -iso p ro p y lid en e -a -D -g a lac to p y ran o se and

re p o rte d an 83^ y ie ld o f 6 -d eo x y -l,2 ,3 ,4 "d i-0 -iso p ro p y lid en e -tt-D -

ga lactopyranose and an u n id e n tif ie d p ro d u c t. When iso p ro p y l a lco h o l

37

CHCbLI

M eCM eC MeOH

CMe.

was su b stitu ted for methanol as so lv e n t , the y ie ld of 6-deoxy-

1 »2,3,4-di-O -isopropylidene-c-D -galactopyranose was 32$ and an

a d d it io n a l p ro d u c t, 6 -d eo x y -l, 2 :3 ,4 -d i-O -iso p ro p y lid en e -L -a rab in o -

hex-5-enopyranose, was o b ta in ed in 36$ y ie ld .

G enera tion o f an aldehyde group was e f fe c te d in a p ro te c te d

sugar by p h o to ly s is o f a p rim ary azide,® â I r r a d i a t i o n of m ethyl

(88a) D. H orton, A. E. Luetzow, and J . C. Wease, i b i d . , 8 ,

366 (1967). (b) D. M. C lode, M. H. M eshreki, H. S h o ji , Chem.

Commun., 694 (1969)•

38

2 , 3 , 4 - t r i - 0- a c e ty l - 6- a z id o -6-deoxy-a-D -glucopyranoside in cyclo-

hexane, fo llow ed by m ild h y d ro ly s is gave 2 ,3 ,4 ~ tr i -0 -a c e ty l-6 -

aldehydo-a-D -g luco-h e x o d ia ld o -l.5 -p y ra n o se . c h a ra c te r iz e d by means«

of i t s (2 ,4 ~ d in itro p h en y l)-h y d razo n e and i t s a c e ty la te d a ld eh y d ro l.

m N

OAcCH.Ac

CHO

OCHAcOOAc

The re a c t io n has been u t i l i z e d fo r p rep a rin g th e 6-aldehydo d e r iv a -88bt iv e o f th e p o ly sacch a rid e am ylose, a component of s ta r c h .

A pho tochem ically induced r in g c o n tra c tio n has been rep o rte d 89by C o llin s . I r r a d ia t io n of a pentano s o lu t io n of m ethyl 6-deoxy-

(89) P. M. C o l l in s , i b i d . , 403 (1968).

2 f3 -0 -iso p ro p v lid e n e -a -L -lvxo -hexopyranosid-A -ulose gave a 60%

y ie ld of two p ro d u c ts . The m ajor p roduct {55%) was id e n t i f i e d as

5 -deoxy-2t 3 -0 -isop ropy lidene-B -D -r ib o ~ furanoside and th e minor

p roduct (5$) was id e n t i f i e d as 5 -d eo x y -2 ,3 -0 -iso p ro p y lid en e-a -L -

ly x o -fu ra n o s id e .

39

9 CH3hv, pen tan e0 - <

-CO

Q JO

c h 3 o c k 1 > n ] 5

OCK.

CMe

■ i

C M e.

+

CMe.

results and discussion

General

In t h i s d isc u ss io n S ec tio n s A, B, and C d ea l w ith p rep a ra

t io n of th e 1 -th io a ld o se d e r iv a tiv e s used . R eactions of c e r ta in

o f th e se p roducts w ith bromine to g ive te tra -O -a c e ty l-p -D -g lu c o -

p y ran o sy lsu lfen y l bromide a re g iven in S ec tio n D. The use o f

n .m .r . spectroscopy t o fo llow th e g e n era l course of th e re a c tio n s

of a range of 1 - th io a ld o se d e r iv a tiv e s w ith bromine i s g iven in

S ec tion E. S ec tions F and G d e a l w ith c h a ra c te r iz a t io n of d is u l

f id e d e r iv a tiv e s and a c e ty la te d g ly co sy l brom ides, r e s p e c t iv e ly ,

as p roducts of th e r e a c t io n o f 1 -th io a ld o se d e r iv a tiv e s w ith bromine

under c e r ta in c o n d itio n s . R eactions fo r c h a ra c te r iz a t io n o f t e t r a -

O -ace ty l-p -D -g lucopy ranosy lsu lfeny l bromides a re g iven in S ec tio n H,

and s im ila r re a c tio n s fo r o th e r a c e ty la te d g ly c o sy lsu lfe n y l bromides

a re given in S ec tio n I . S ec tions J and K d e a l w ith th e p h o to ly s is

o f d im ethy lth iocarbam ates o f su g a rs .

A. A cety la ted g ly co sy l h a lid e s

The a c e ty la te d g ly co sy l bromides were p rep a red d i r e c t ly

from th e f r e e a ld o ses e s s e n t ia l ly accord ing to th e procedure of

B arczai-K artos and K o ro s y ,^ The p h y s ic a l d a ta m easured on th e

(90) M. B arczai-M artos and F. Korosy, N a tu re , 165, 3&9 (1950).

ho

4 i

p ro d u cts were in good agreem ent w ith values in th e l i t e r a t u r e , A

summary o f th e mode of c h a ra c te r iz a t io n o f th e a c e ty la te d g ly co sy l

bromides i s g iven in Table 4-.

T ri-O -acetyl-a-D -xylopyranosyl chloride (5) was prepared97acco rd ing to th e method o f Hudson and Jo h n so n ,7 The compound

(97) C. S . Hudson and J . M. Johnson, J . Amer. Chem, S o c .,

22, 274.8 (1915).

gave a m.p. and r o ta t io n corresponding w ith th e known v a lu e s .

The method used f o r th e p re p a ra tio n o f 3 ,4 ,6 - t r i - O - a c e ty l -

2 -0 - tr ic h lo ro a c e ty l-p -D -g lu c o p y ra n o sy l c h lo rid e (6) was e s s e n t ia l ly98 99th a t adapted by Lemieux and Howard and Lemieux and Huber from

th e o r ig in a l p rocedure o f B r ig l ,^ ® The r e p o r t e d ^ y ie ld of^40 g

(98) R. U, Lemieux and J . Howard, Methods in Carbohyd.

Chem., 2 , 400 (1963).

(99) R. U. Lemieux and G. Huber, Can, J . Chem,, 31,

1040 (1953).

(100) P . B r ig l , Z. P h y s io l. Chem., 116, 1 (1921).

was im possib le t o re p e a t by th e co n d itio n s g iven and th e l i t e r a t u r e

v a lu es o f m.p. 140-142°, La 3j) +8.9° (c 1 .4 , c h lo ro fo rm )^ were

only ob ta ined a f t e r two r e c r y s t a l l i z a t i o n s o f crude 6 from e th e r .

Compound 6, which was d i f f i c u l t t o c r y s t a l l i z e , was only ob ta ined

c r y s ta l l in e by p e r io d ic a g i ta t io n o f th e co ld e th e re a l

TABLE X

ACETXLATED GLICOSYL BROMIDES

Compound Mode o f c h a ra c te r iz a tio n L ite ra tu re re fe ren ce

m .p .; [ajpCCHCl^); o ther

T etra -O -ace ty l-a -D -glucopyranosyl bromide ( l ) 88-89° +198° n*ni#r • 91,92

T etra-O -ace ty l-a -D - galac topyranosy l bromide (2)0m 82-83° +213° n.nu r • 93 ,92

T ri-O -a ce ty l-p -L -a ra b in o - pyranosyl b ro lid e (3)0m 138-1X0° +279° 9X,92

T ri-O -ace ty l-a -D -xy lo - pyranosyl broSide (X)0m 101-102° +211° 95,96,92

(91) R. U. Lemieux, Methods Carbohyd. Chem., 2 , 221 (1963).

(92) D. Horton and tf. N. T urner, J . Org. Chem., 20 , 3387 (1965).

(93) J . Conchle and G. A. L ew y, Methods Carbohyd. Chem., 2 , 336 (1963).

(9X) M. Gehrke and F. X. A ichner, B e r ., 69, 918 (1927).

(95) F. Weygand, Methods Carbohyd. Chem., 1 , 182 (1962).

(96) J . K. D ale, J . Amer. Chem. S o c ., 27, 27X5 (1915).

43

c r y s ta l l i z in g m ixture over a two day p e rio d . Various m o d ifica tio n s

of th e method, in c lu d in g p u r i f ic a t io n of th e s t a r t in g m a te r ia l,

(pen ta-O -acety l-p -D -g lucopyranose, 7 ) , and in c re ased tim e of evapora

t io n under vacuum a t an e le v a te d tem pera tu re o f 85° to e lim in a te

unwanted s id e p ro d u c ts , d id not in c re a se th e y ie ld o f 6.

3 ,4 ,6 -T ri-p -ac e ty l-p -D -g lu co p y ra n o sy l c h lo rid e (8) from

3 ,4 ,6 - tr i-p -a c e ty l-2 -p - tr ic h lo ro a c e ty l-p -D -g lu c o p y ra n o s y l ch lo rid e

was p repared by B r ig l 's ^ ® method as d esc rib ed by Lemieux and

H ow ard .^ The rep o rte d va lues f o r th e m.p. and r o ta t io n were

ob ta ined a f t e r a len g th y p u r i f ic a t io n p ro cess fo r th e g lucopyranosyl

ch lo rid e (8 ) ,

B. P re p a ra tio n o f 2 -g ly co sy l-2 - th iopseudourea hydrohalides

The 2 - (a c e ty la te d g lycopy ranosy l)-2 -th iopseudou rea hydro

h a lid e s were p repared accord ing to th e method of Cerny, Vrkoc, andI tj

Stan&k, (a m o d ifica tio n o f th e o r ig in a l procedure o f Schneider

and E is fe ld ^ 1'*). The a c e ty la te d g ly co sy l h a lid e s were condensed w ith

th io u re a in acetone to g ive th e corresponding th iopseudourea hydro

h a lid e d e r iv a t iv e s . A summary o f th e mode o f c h a ra c te r iz a t io n of

th e th iopseudourea hydrohalides i s given in Table 5.

An attem pt was made to o b ta in 100 MHz n .m .r . sp e c tra o f

th e 2 -g ly co sy l-2 -th io p seu d o u rea hydrohalide d e r iv a tiv e s in d e u te r

ium oxide s o lu tio n w ith sodium 2 ,2 -d im e th y l-2 -s ila p e n ta n e -5 -s u l-

fo n a te (DSS) as an in te r n a l s tan d a rd and to c o r r e la te the s t ru c tu re

of each compound w ith i t s n .m .r . d a ta . Compound 9 p r e c ip i ta te d

TABLE 5

2-GLYC0SYL-2-THI0FSEUD0UREA HIDROKALIDES

Mode o f c h a ra c te r iz a tio n L ite ra tu re re fe ren ceCompound m.p. [ a ] D o th e r

2 - (2 ,3>4 »6- t e t r a -0 -ace ty l-P -D - glucopyranosyl)T2- th io - “ pseudourea hydrobromide (£) 205° -8 .7 ° (HÔ) 45 ,46 ,47

2 - ( 2 ,3 A »6 - t e t r a - 0- a c e ty l i3- D -galactopyranosy l)-2 - th iopseudourea hydrobromide( io )

„ o169-5 +16.9° (BtOH) n .m .r . 46,

2- ( 2 ,3 ,4 - t r i- J J -a c e ty l-a - L-a rab inopyranosy l) - 2 -th iopseudourea hydrobromide (11) 174-173° +6 . 8° (IÔ) n .m .r . 39

2 -(2 >3 ,4—1t r i-O -a c e ty l-p - D -xylopyranosyl)- 2-th iopseudourea hydrobromide ( 12 ) _ h.o

173 - 36° (HgO) 48

2 -(2 ,3 » 4 - tr i~ <O -acetyl-0 - D -xylopyranosyl)- 2-th iopseudourea hydroch loride (13) 181° - 89° ( 1 0 ) n .m .r . k6

45

from s o lu t io n when a s u f f ic ie n t amount o f DSS was added to o b ta in a

lo c k s ig n a l f o r th e 100 MHz n .m .r . sp ec tro m ete r. N .m .r. sp e c tra

were o b ta in ed fo r compounds 10, 11, 12, and 13* -As was a n t ic ip a te d ,MfW Msf MWth e p ro to n s a tta c h e d to th e n itro g e n atoms underwent deuterium ex

change w ith th e so lv e n t and t h e i r s ig n a ls were not observed . In

each case th e n .m .r . spectrum was no t amenable to complete f i r s t -

o rd e r a n a ly s is , bu t p a r t i a l an a ly ses made were based upon known chemi-

39c a l - s h i f t d a ta fo r a c e ty la te d 1 -th io -a ld o p y ra n o se s .

The r in g p ro tons of th e 2 -g a la c to sy l-2 -th io p seu d o u re a hydro

bromide (10) gave r i s e to a 4 -p ro to n m u lt ip le t a t 1*4.39-4*77 Qnd aMM3 -p ro to n m u lt ip le t a t 1*5.45-5.85. The lo w -f ie ld m u lt ip le t was

a ss ig n e d to H -l, 2 , 3 , and 4 nnd th e h ig h e r - f ie ld m u lt ip le t was

a ss ig n e d to H-5, 6 , and 6*. The h ig h e r - f ie ld m u lt ip le t was p a r t i a l l y

masked by appearance o f th e HOD s ig n a l . The methyl p ro tons of

th e a c e ty l groups o f 10 were a ssig n ed to fo u r sharp s in g le t s , a t T7.79,

7 .8 6 , 7 .9 1 , and 7 .9 8 . No attem pt was made to a ss ig n th e se s ig n a ls to

s p e c i f i c a c e ty l g r o u p s ." ^

(101) D. Horton and J . H. L auterbach, J . Org. Chem., 34,

86 (1969 ).

The n .m .r . spectrum o f 2 - ( t r i - 0 - a c e ty l - a -L -a r a b in o s y l) - 2 -

th io p seu d o u rea hydrobromide 11 showed a lo w -f ie ld m u lt ip le t T4.44-MM4 .7 9 . This m u lt ip le t was assigned to H -l, 2 , 3 , and 4 . Two

q u a r te ts a t h ig h e r f i e l d , T5.76 and 5.97 were d esig n a ted as H-5a

(low er f i e l d ) and H-5b (h igher f i e l d ) . The J , f. coup lings were

th en J . _ = 3 .2 Hz, J = 1 .8 Hz, and J = 13 .0 Hz. These " 4 ,5a 4 ,5b 5a,5bco n stan ts were in agreement fo r those rep o rte d -^ for* a benzene-d^

S o lu tio n o f 1 -th io -a -L -a rab in o p y ran o se te t r a a c e ta te (1 4 ), which

showed ^ = 3 .9 Hz, 5b = 2 .0 Hz, - 12 .4 Hz. The pro tons

a t C-5 were no t c le a r ly d i f f e r e n t ia te d as e q u a to r ia l o r a x ia l s in c e

bo th o f th e se p ro tons are gauche-disposed to th e v ic in a l p ro tons a t

C-4.

The n .m .r , sp e c tra o f the 2 -D -xy lopyranosy l-2-th iopseudourea

hydrobromide 12 and th e 2-D -xylopyranosy l-2 -th iopseudourea hydro

c h lo r id e 13 were s im ila r . Each showed a doub let a t T4 .2 6 assigned

t o H -l w ith a spac ing of 5 .0 Hz. The m u lt ip le ts a t T4 . 6 8 -5 .13 and

T4 . 66-5 .16 were a ssig n ed to H-2, 3 , and 4 o f th e re s p e c tiv e compounds

12 and l ^ . Two q u a r te ts a t h ig h er f i e l d , T 5 .6 0 and T6.17 in th e

case o f 12 and T5.59 and T6.17 in th e case o f 13 , were desig n a ted

as H-5a (low f ie ld ) and H-5b (high f i e ld ) fo r th e low and high f i e l d

H-5 p ro to n s of each compound. The coupling c o n stan ts f o r J . _ ,

”4 5b* and "5a 5b were s jniâ r fo r exam ples, th u s fo r 12,

"4 5a ~ 3 '^ - 4 5b = and ^5a 5b Hz, ôr £3-4 5a ~ ^ -9 Hz, = 6 .1 Hz, and J^ & ^ = 12 .3 Hz. The sm all

coup ling c o n stan ts f o r J - ^ and and ^ fo r 12 and 1^, com

p ared w ith those f o r a chloroform -d s o lu t io n o f 1 -th io -p -D -x y lo -

pyranose t e t r a a c e t a t e 39 (15) (£, _ = 8 .1 Hz, J . _ = 4 .7 Hz, and

"4 5a = ^*3 in d ic a te d th a t th e re i s v e ry p robably a conforma

t io n a l e q u ilib riu m between c h a ir conformers fo r 12 and 13 , w ith th e

observed spectrum re p re se n tin g a tim e average o f th e c h a ir conformers

in

p re se n t in comparable amount.-*-02,103 p o la r e f f e c t of th e

(102) P . L. D urette, D. Horton, and N. S. Bhacca, Carbohyd.

R e s ., 10, 565 (1969).

(103) P . L. Durette and D. Horton, Chem. Commun., 516 (1969).

H 0 NH

Br o r C

OAcAcO

B ro r Cl'

S -s u b s ti tu e n t would account f o r a g re a te r amount o f th e 1C (d)

conformer f o r 12 o r 13 as opposed to th e r e l a t iv e ly minor amount

of 1C (g) conformer observed in the n .m .r . s tu d y of 1-thio-jS-D -

xylopyranose te tra a c e ta te -77 (1 5 ). A more complete n .m .r . study

of 2 -g ly co sy l-2 -th io p seu d o u rea hydrohalides of t h i s type needs

to be made befo re meaningful conclusions can be ob ta ined .

C. P e ra c e ty la te d 1 - th io sugars

a . From a c e ty la te d 2 -g lycosy l-2 -th lopseudou rea hydro-

h a l i d e s ,—The method fo r p re p a ra tio n of most of th e p o ly a c e ty la te d

1 - th io sugars was th a t of Cerny, Vrkoc, and S ta n e k .^ This method

invo lved th e decom position of th e 2 -g ly co sy l-2 -th iopseudou rea

hyd ro h alid es to th e corresponding 1 - th io l by sodium hydrogen s u l

f i t e , fo llow ed by a c e ty la t io n of th e re s u l t in g th io l w ith p y rid in e

and a c e t ic anhydride. The compounds prepared in t h i s manner a re

g iven in Table 6 .

1-T hio-p-D -glucopyranose p e n ta a c e ta te ^ (16) and 1 - th io - c -39L -arabinopyranose te t r a a c e ta te ( l£ ) have p re v io u s ly been p repared

from t h e i r corresponding 2 -g ly co sy l-2 -th io p seu d o u rea hydrobrom ides./Q

The corresponding th io l has been p repared from 2 -D -g a lac to sy l-2 -

th iopseudourea hydrobrom ide, but to th e a u th o r’s knowledge t h i s

p re p a ra tio n of 1 -th io -p -D -g a lac to p y ran o se p e n ta a c e ta te i s th e f i r s t

complete tran sfo rm a tio n o f 10 in to 17. This p rocess a ls o re p re se n ts

th e f i r s t p re p a ra tio n of 1 -th io -p-D -xylopyranose t e t r a a c e ta te (15)

from th e 2 -xy lopyranosy l-2 -th iopseudourea hydrobromide 12 and th e

hyd roch lo ride 13.MMb . From a c e ty la te d a ld o s e s .—The a c id -c a ta ly z e d e q u il ib ra

t io n of pen ta-O -acety l-p-D -g lucopyranose p e n ta a c e ta te (7) w ith z in c

c h lo r id e in th io la c e t ic a c id gave 92% y ie ld of c r y s ta l l in e 1 -th io -p -B -

g lucopyranose p e n ta a c e ta te (16 ). The compound was id e n t i f i e d by

comparison o f th e m .p ., o p t ic a l r o ta t io n , and n .m .r . spectrum w ith

th a t p re v io u s ly re p o rte d in th e l i t e r a t u r e . 39,42,43 n . m#r#

spectrum (60 MHz) of th e crude re a c tio n product showed only th e

TABLE 6

PERACETTLATED-1-THIO SUGARS

Compound Mode

m .p .;

of c h a ra c te r iz a tio n

[ a ] D(CHCl3) ; o ther

L ite ra tu re re fe ren ce

1-Thio-p-D -gluc opyranose p e n ta ac e ta te (16) 118-119° +10° n .m .r. 39 ,42,99

1-T hio-p-D -galact opyranos e p e n ta ac e ta te (17)

M M114-115° +30.1° n .m .r . 39

1-Thio-a-L-arabinopyranose te t r a a c e ta te (14)

MM77-78° +33.3 n .m .r . 39

1-Thio-p-D -xylopyranose te t r a a c e ta te (15)

m m99-100° -7 .0 ° n .m .r .

j 39,41

p resence of 1-th io-B -D -glucopyranose p e n ta a c e ta te (16) and no

s ig n a l -was v i s ib le a t low f i e l d (T3 . 76) th a t would have in d i

c a te d th e presence o f l- th io -a -p -g lu c o p y ra n o se p e n ta a c e ta te (18 ).

The method employed fo r th e e q u il ib ra t io n re a c tio n was analogous

t o t h a t d e sc rib e d by Wolfrom and Thompson^ fo r th e m ercap to lysis

o f p -D -fru c to se p e n ta a c e ta te with e th a n e th io l and a Lewis a c id

(z in c c h lo r id e ) and to th e method d escrib ed by Wood, Coxon, D ieh l,70and HLetcher fo r th e p re p a ra tio n of t e r t -b u ty l 1 -th io -p -D -g lu co -

pyranose t e t r a a c e ta te (1 9 ). L em ieux^ ob ta ined a 71 .2^ y ie ld of

e th y l te tra -O -a c e ty l- l- th io -p -D -g lu c o p y ra n o s id e by th e z inc

c h lo r id e -c a ta ly z e d m ercap to ly sis o f 7 w ith e th a n e th io l . The re a c - 66 67t io n i s thought ' to proceed by a ro u te analogous t o th a t o f

th e e th a n e th io l w ith m ercap to ly sis of p-D -glucopyranose p e n ta a c e ta te

(7 ) . Loss o f th e 1 -ace to x y group w ith synchronous p a r t i c ip a t io n of

th e 2 -ace to x y group forms a c y c lic carbonium io n . The carbonium

ion i s th en a tta c k e d by th e su lfu r atom o f th io la c e t i c a c id .

u PAcOCH, AcOCHj7—0 f » il-bSA c

\O A c )k ~ A c O ^ — Y Q

n - C C R

The method o ffe rs a p o te n t ia l rou te fo r a one-step p rep a ra tio n

of 1 ,2 - t r a n s p e ra c e ty la te d 1 - th io a ld o p y ra n o s id e s .

c . By re a c tio n o f potassium th io la c e ta te w ith 3 .4 ,6 - t r i -O -

ace tv l-B -D-plncopvranosyl c h lo r id e ( 8 ) .—The p re p a ra tio n of 1 - th io -

a-D -glucopyranose p e n ta a c e ta te (18) p re se n ts s p e c ia l problems because— mwth e s u b s ti tu e n ts a t C-l and C-2 are .c is -d isp o se d . Potassium t h i o l

a c e ta te was condensed w ith 8 in acetone and th e product was a c e ty la te dUaccording to th e procedure o f Tejima .et a l . The d e s ire d 1 - th io -o -

D-glucopyranose p e n ta a c e ta te (18) was i s o la te d from a m ixture o f

th re e p ro d u c ts and th e m.p. and s p e c if ic r o ta t io n were c o n s is te n t

w ith th e v a lu es o f Tejima e t a l , ^ The r o ta t io n , [ a ] ^ +135° (c 1 ,0 ,

ch lo ro fo rm ), d i f f e r e d somewhat from th a t re p o rte d by Schneider and

c o -w o rk e rs ,^ [a ] ^ +120.2° (c 0 .416 , ch lo ro fo rm ). The German 52 . ~workers ob ta ined 18 by a c e ty la t in g a m u taro ta ted sample of 1 - th io -

p-D-glucopyranose and s e p a ra tio n of th e m ixture of p ro d u c ts . T heir

p roduct may no t have been se p a ra ted com pletely from th e p-D anomer.

The s ig n a l observed f o r H-l in the 60 MHz n .m .r . spectrum

of th e 1 - th io -a -D -p e n ta a c e ta te 18 in chloroform -d was an apparent— MWq u a r te t (T3.76) having sp ac in g s of about 1 .2 Hz. When th e spectrum

was measured a t 100 Mz, th e s ig n a l f o r H-l was observed as a . t r ip l e t

having spacings o f about 2 ,1 Hz. When th e so lv e n t was changed to

benzene-d^ th e H -l s ig n a l appeared as a sharp d o u b le t, T3»49,

2 = p e rtu rb e d s ig n a l fo r H-l in chloroforra-d was

a t t r ib u te d to v i r tu a l coup ling of H -l w ith H-3 as th e r e s u l t o f close

p rox im ity of th e H-2 and H-3 s ig n a ls .10^ 106 For f u r th e r d e ta i l s

of th e n .m .r . s p e c tra of 18 se e the Experim ental sec tioD .

52

(104.) J . I . Musher and E. J . Corey, T etrahedron , 18, 791

(1962).

(105) N. S, Bhacca and D. H. "Williams, A p p lica tio n s of UMR

Spectroscopy in Organic C hem istry , Holden-Day, I n c . , San F ra n c isco ,

C a l i f . , 1964, p . 36.

(106) R, U. Lemieux and J . D. S tevens, Can. J . Chem., 43.

2059 (1965).

d . P re p a ra tio n of phenyl (20) and benzyl 2 ,3 ,4 ,6 - te t r a -O -

a c e ty l- l- th io -p -D -g lu c o p y ra n o s id e (2 1 ) .—These compounds, 20 and 21,■ ...... - ■ = .............. « ■ ■ ■ mw *

were p rep a red by condensation o f th e corresponding b en zen th io l and

a - to lu e n e th io l w ith te tra -O -ace ty l-a -D -g lu co p y ran o sy l bromide ( l ) .

The p h y s ic a l c o n s tan ts ob tained were in agreement w ith rep o rte d

v a lu es fo r 2(P®*^ and 2l | 7 * ^MM

D. T etra-O -ace ty l-p -D -g lucopy ranosy l- su lfe n y l bromide ” (22)

The o r ig in a l p re p a ra tio n of te tra -O -a c e ty l-p -E -g lu c o p y ra n o sy l-

s u lfe n y l bromide ( 2 2 ) ^ was d e sc rib e d in th e a u th o r 's M aster ofMM

Science t h e s i s . ^ The s u lfe n y l bromide 22 was a ls o ob ta ined byMM **

brorainating t e r t - b u ty l 1 -th io -p -D -g lucopyranose t e t r a a c e ta te (19)-^ Mm

* no rf/1 ngThe compound I s o la te d was id e n t ic a l w ith an a u th e n tic sample of 22 9 *

by comparison of p h y s ic a l c o n s ta n ts , and was c h a ra c te r iz e d by trap p in g

w ith b en ze n e th io l to g ive the known phenyl te tra -O -a c e ty l-p -D -

g lucopyranosy l d is u lf id e (23) . 73 ,7 8 Form ation of th e su lfe n y l

53

bromide 22 from th e te r t .-b u ty l th io -D -g lu co sid e 19 as w ell as from

AcOCH^ AcOCHj. AcOCH^.q SCMe3 J— q SBr J— q SSPh

1 ' Brx ' . / \ | PhSHCCL \OAc

4 Ac

th e th io la c e ta te 16 , support th e m echanistic r a t io n a le (se e Scheme I )

o r ig in a l ly p ro p o se d ^ fo r th e fo rm ation of the su lfe n y l bromide 22,

based on th e h e te ro ly s is o f an in te rm e d ia te bromosulfonium ion a t

p o in t b , i f R+ i s a c a tio n more s ta b le th an th e g ly co sy l c a tio n th a t

would r e s u l t from s c is s io n a t p o in t a . The r e a c t io n re q u ire s more

th an one m olecule o f bromine p e r m olecule; th e re fo re , th e a c tu a l

t r a n s i t i o n s t a te may invo lve an a d d it io n a l m olecule o f bromine th a t

in te r a c t s w ith th e bromosulfonium io n . Conversion of th e su lfe n y l

bromide 22 in to th e te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l bromide U )

i s , p re d ic ta b ly a slow er p ro cess than form ation o f 1 . becauso th eM *

s u lfu r atom in 22 would be expected t o be much l e s s su sc e p tib le t o

a tta c k by (p o s i t iv e ) bromine th an th e s u lfu r atom in th e th io a c e ta te

J.6 or th io -2 -g lu c o s id e 19. I t was decided to in v e s t ig a te th e brom in-

a t io n of a number o f a c e ty la te d 1 -th io a ld o p y ran o ses and a c e ty la te d

1 -th io g ly c o s id e s and to a ttem p t to fo llow the re a c t io n by th e use

o f n .m .r . spectroscopy .

54

AcO

SB r

AcOa_-RSBr

Br (slow)

BrSBr-SBr

AcO'

0 . 0Br

BrAcOAcO

Scheme I . —M echanistic r a t io n a le f o r fo rm ation of te tra -O - a c e ty l-p -D -g lu c o sy lsu lfe n y l bromide (22) and te t r a -O -a c e ty l- a -p - g lucopyranosy l bromide ( l ) .

55

S. N .m .r. s p e c t r a l s tu d ie s o f th e brom ination o f various a c e ty la te d 1 -th io a ld o se d e riv a t iv e s in carbon te t r a c h lo r id e

a . For l - th io -p -D -glucopyranose p e n ta a c e ta te 1 6 .—Treatm ent

o f th io a c e ta te 16 w ith a 6 .3-fflolar excess of bromine caused complete

cleavage of th e S -a c e ty l group from ^ w ith in 1 rain, as shown by th e

d isappearance o f th e 3**proton s in g le t a t ^7.59 (SAc) observed in

th e spectrum o f 1J5, flad th e appearance o f a s ig n a l corresponding t o

a c e ty l bromide a t T7.19. T e tra -O -ace ty l-a -D -g lucopy ranosy l bromide

(i) was d e f in i te ly ab sen t from th e re a c tio n m ixture a t t h i s s ta g e ,92

because no lo v - f ie ld doub le t ( f o r H -l o f 1) was observed in the

spectrum . The spectrum in d ic a te d th e p roduct was th e su lfe n y l

bromide 22. The d a ta from e lem en ta l a n a ly s is and th e r e a c t iv i ty o f

AcOCH AcOCH AcOCHOSAc

Br; Br,OAc OAc OAc

J B r OAc

AcO AcO AcOOAc OAc

16 22 1

th e p roduct i s o la te d c le a r ly e s ta b l i s h th a t i t i s 22 and no t

b is ( te tra -O -a c e ty l-p -D -g lu c o p y ra n o sy l) d is u l f id e (24 ).*^ The n .m .r .

s p e c tra of the su lfe n y l bromide 22 and th e d is u l f id e 24 d i f f e r on ly

in m inor d e t a i l s , and in n e i th e r case can th e H^l s ig n a l be observed

c le a r ly to the lo w -f ie ld s id e o f th e 11 envelope" of s ig n a ls fo r th e

m ethine p ro to n s , because th e s u l f u r atom a t C-i e x e r ts a much

sm a lle r d e sh ie ld in g e f f e c t th an an oxygen or halogen atom .39

b . For l - t h i o - g -D-glucopyranose p e n ta a c e ta te (1 8 ) .—As in

th e case o f 16. trea tm en t o f th io a c e ta te 18 w ith a 7-m olar excess

o f bromine a t 34° caused c leavage of most o f th e S -a ce ty l group

from 18 w ith in 1 min as shown by th e d isappearance o f th e 3 -p ro to n

s in g le t a t T7.60 (SAc) observed in th e spectrum of 18, and th e

appearance of a s ig n a l a t T7.19 th a t corresponded to a c e ty l brom ide.

A lo w -f ie ld doublet was p r e s e n t , T4.12 having a coupling co n stan t

of 4 .0 Hz. The s ig n a l fo r H -l of 18 was no t observed in th e i n i t i a l

spectrum b e fo re b rom ination due to th e low s o lu b i l i t y o f 18 in c a r

bon t e t r a c h lo r id e , however H -l o f 18 gave a complex s ig n a l a t T3.76*

in chloroform -d. I t i s no t l i k e l y th a t th e change in so lv e n t sy s

tems from chloroform -d to carbon te t r a c h lo r id e would cause a s h i f t

of t h i s magnitude fo r th e H -l s ig n a l . An a d d it io n a l lo w -f ie ld

d o u b le t, T 3 .28 , 2 = Hz of> t e tr a -0 -a c e ty l-a -5 -g lu c o -

pyranosy l b ro m id e ^ ) was p re s e n t in l e s s than 55 sec a f t e r broraina-

t io n and th e s ig n a l a t T7.60 (S -a c e ty l) had com plete ly d isappeared .

The s ig n a l a t '*'4.12 g ra d u a lly decreased in in te n s i ty and th e s ig n a l

a t *3.28 in c re a sed in in te n s i ty u n t i l th e lo w -f ie ld doublet was th e

only s ig n a l observed. Three compounds th a t could conceivab ly ac

count fo r th e doublet a t T 4 .12 , a re te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l-

bromide (2j>), b is(a -D -g lu co p y ran o sy l) d is u l f id e o c ta a c e ta te (2 6 ) ,

and te tra -O -a c e ty l-p -D -g lu c o p y ran o sy l bromide (27 ). German

w orkers-^? re p o rte d th e H -l s ig n a l as p a r t o f a m u lt ip le t , T 4.6 -5 .0

(107) K. Heyns, W. T rau tw ein , F. G. E sp inosa , and

H. P au lsen , B e r . , 22» 1183 (1966).

57

A c O C h ^

AcOCH AcOCH

AcO OAc18 25«"<M AcOCHo r

)AcAc

OAc27«v*

f o r a chloroform -d so lu tio n o f 27. They observed th e H -l s ig n a l

o f 27 by d is so lv in g th e compound in a c e to n i t r i l e fo llow ed by a d d i

t io n of tetramethylammonium c h lo r id e . No chem ical s h i f t was

reco rded for- H -l because th e s h i f t changed w ith c h lo r id e - io n concen

tra t io n } however, a coupling co n stan t of 8 Hz was reco rd ed . Thus,

th e doublet a t T4 .1 2 cannot be a t t r ib u te d to H -l of 27.

The th io a c e ta te 18 was converted alm ost e n t i r e ly in to th e

a-D -glucopyranosyl bromide 1 in l e s s than 1 h r a t 3 4 ° , as d e te r

mined by th e in te g ra te d in te n s i ty o f th e H -l s ig n a l r e l a t iv e to th a t

o f th e a c e ty l methyl p ro to n s . I s o la t io n of 1 from th e re a c tio n

m ixture in a y ie ld o f 36% s u b s ta n t ia te d th e conversion of 18 in to 1 .

Q u a n tita tiv e i s o la t io n of 1 was d i f f i c u l t due to th e i n s t a b i l i t y o f 1 ,

to p o ss ib le decom position on s i l i c a g e l, and f a i lu r e to c r y s ta l

l i z e in th e p resence o f minor im p u r it ie s . T . l . c . showed 1 as th e

m ajor re a c tio n p ro d u c t.

c . For 1 -th io -p -D -ga lac topy ranose p e n ta a c e ta te (17) ,

1 -th io -a -L -a rab in o p y ran o se te t r a a c e ta te ( l £ ) , 1 -th io -p -D -x y lo -

pyranose t e t r a a c e ta te (1 5 ), and l- th io -p -p - r ib o p y ra n o se t e t r a

a c e t a t e ^ ( 2 8 ) .—Treatment of th e 1 - th io a c e ta te s , 17 . 14-, 15.___ ^ 7 MM1 7

and 28, in carbon te t r a c h lo r id e w ith 7 , 4 .2 , 5 .9 and 5 .9 molart, MM * * *

eq u iv a len ts of brom ine, re s p e c t iv e ly , caused complete cleavage of

th e S -ace ty l groups a t a r a te f a s t e r than was m easurable by th e

n .m .r , techn ique d e sc rib e d . The appearance of s ig n a ls corresponding

to a c e ty l bromide and t o H-l fo r th e re sp e c tiv e a c e ty la te d g lycosy l

h a lid e s were observed in each experim ent. In te g ra tio n of th e

AcOCH2

W Q BrzCCL

AcOCHAcO/* O-

BrOAc

B r-

CCl

AcOOAc

Br

59SAc

OAcAcO

OAc

B r ,

CCL OAcB rA c

QAc

15

SAc

AcOAc

28

BrzCCL

O B r

AcO OAc

s p e c tra , in l e s s th an 10 rain a f t e r b ro m in a tio n , in d ic a te d complete

conversion of th e th io a c e ta te s I n to t h e i r re s p e c tiv e a c e ty la te d g ly -

cosy l h a lid e s as determ ined by th e in te g ra te d i n te n s i t i e s of th e H-l

s ig n a ls r e l a t iv e to th o se o f the a c e ty l methyl p ro to n s . T . l . c . in d i

ca ted th a t th e m ajor r e a c t io n component was th e a c e ty la te d g ly co sy l

h a lid e and th e id e n t i ty o f th e re a c t io n p roduct was v e r i f i e d by i s o

la t i o n o f th e a c e ty la te d g ly co sy l h a lid e in each experim ent.

d . For phenyl 2 . 3 .4 .6 - t e t r a -O-a c e ty l - l - t h i o - a -D-glucopyrano-

s id e (20) and benzyl 2 ,3 .A .6 - te t r a - 0 - a c e ty l - l - th io - p -D-glucopyranoside

( 2 1 ) .—B o n n er^ had p re v io u s ly d e sc rib e d th e brom ination o f 20 in

a c e tic a c id to y ie ld te tra -O -a c e ty l-a -D -g lu c o p y ra n o sy l bromide ( l ) .

This n .m .r . s p e c t r a l s tu d y a ls o shows th e fo rm ation o f 1 . O ther 69*108,109

workers showed th a t v a rio u s a c e ty la te d a lk y l th io g ly c o s id e s

gave g ly co sy l bromides on b rom ination .

60

(108) F . Weygand, H. Ziemann, and H. J . Bestmann, B e r ., 21,

2534- (1958).

(109) H. Z inner, A, K oine, and H. Nimz, i b i d . . 93 , 2705

(I960).

The i n s o lu b i l i ty o f the phenyl 1 - th io g lu c o s id e 20 in carbonMMt e t r a c h lo r id e made the b rom ination re a c t io n d i f f i c u l t t o fo llo w . A

scan o f th e n .m .r . spectrum was i n i t i a t e d 40 sec a f t e r th e a d d it io n

o f bromine to th e suspension of 20 and a lo w -f ie ld doublet was ob-WMse rv e d fo r H -l o f te tra -O -ace ty l-a -D -g lu co p y ran o sy l bromide ( l ) .

I n te g ra t io n a f t e r 7 min in d ic a te d complete conversion of 20 in to 1 .

AcOCHSPh

OAcAcO

CAc

AcOCH

B ri■> CAcCCI Ac

CAc2 0 1#>W A* ^

T . l . c . of th e re a c t io n product showed th e m ajor r e a c t io n product

t o be 1 and i s o la t io n o f c r y s ta l l in e 1 confirm ed th e id e n t i ty o f

th e r e a c t io n p ro d u c t.

B rom ination of th e benzyl 1 -th io -D -g lu c o s id e 21 in carbon— M M

te t r a c h lo r id e a t 34° caused complete cleavage o f th e benzyl group

from 21 w ith in one min a s in d ic a te d by th e s h i f t o f th e ben^ylic CH2

pro to n s from T6.44 t o T5.77. No lo w -f ie ld doublet fo r H -l o f th e

g ly co sy l h a lid e 1 was observed u n t i l 7 min 30 sec a f t e r b rom ination .

At t h i s tim e th e H -l s ig n a l o f ^ began to appear. A fte r 25 min th e

H -l s ig n a l o f 1 had an in te g ra te d in te n s i ty o f 0 .34 r e l a t i v e to th e

a c e ty l p ro to n s and a f t e r 1 h r 30 min th e in te g ra te d in te n s i ty of

th e H -l s ig n a l in c re a se d to 1 . T . l . c . of th e re a c t io n m ixture showed

th e g ly co sy l h a lid e 1 was th e major re a c t io n product o f extended

brom ination o f 21. The re a c t io n p roduct was v e r i f i e d as 1 when i tM Wwas i s o la te d in c r y s ta l l in e form.

of 21 and th e absence a t th a t tim e o f a lo w -f ie ld s ig n a l fo r th e

g ly co sy l bromide 1 suggest th a t th e su lfe n y l bromide 22 was formed

i n i t i a l l y . However i f th e s u lfe n y l bromide had been p re sen t a t

t h i s p o in t i t would c e r t a in ly have been converted in to th e g ly co sy l

bromide 1 a t th e r e l a t i v e ly slow r a te d e sc rib ed fo r th e conversion

of 22 in to 1 in th e b rom ination of 1 -th io -p -D -g lucopyranose p e n ta

a c e ta te (1 6 ). P o s s ib ly , th e re a c tio n proceeds by brom ination o f th e

The immediate s h i f t o f th e b e n zy lic p ro tons upon brom ination

AcOCH AcOCH AcOCHSCHPh

B r

21 1

b en zy lic CH„ p o s i t io n of th e th io g ly c o s id e 21* fo llow ed by(L ~ mm

brom ina tion of th e r e s u l t in g sp ec ie s to g ive th e g lycosy l

h a lid e 1 .

e . For 2 ,3 ,4 ,6 - t e t r a -Q-a c e ty l - l -S -b e n z o y l- l- th io -p -D -

g lucopyranose (29) . —Treatment of th e 1 -th io b en zo a te 29 w ith

bromine was d i f f i c u l t to fo llow because of th e i n i t i a l in s o lu

b i l i t y o f 29 in carbon te t r a c h lo r id e . A s ig n a l o f low in te n s i ty

was p re se n t fo r H -l of th e g lu co sy l bromide 1 a f t e r 1 min. The

lo w -f ie ld doublet was c le a r ly v i s ib le 2 min 20 sec a f t e r th e»

a d d it io n o f brom ine. The in te g ra te d in te n s i ty of th e lo w -f ie ld

AcOCHAcOCHAcOCH*SB rSCPh

Br,OAcOAcOAc CCiCC1 4 AcO B r

>AcAcAc

OAcOAc12229

doub le t r e l a t i v e t o th e a c e ty l methyl s ig n a l was 1 a f t e r 7 min.

T . l . c . o f th e r e a c t io n m ixture showed 1 as th e major re a c tio n

p roduct and th e conversion of 29 to 1 was v e r i f ie d by is o la t io n

o f c r y s ta l l in e te tra-O -acety l-a r-D -g lucopy ranosy l bromide 1 .— AT

F. Form ation of b is { te tra -0 -a c e ty l-p -D - g lucopyranosyl) d is u l f id e (2A) and b is ( te tra -O -a c e ty l-p -D -g lu c o p y ran o sy l) d is u l f id e mono-oxide T30)

Treatment of t e r t -b u ty l 1 -th io -p -D -g lucopyranoside t e t r a

a c e ta te ( lg ) in carbon te t r a c h lo r id e w ith dropwise a d d itio n of

bromine during 3 hr ( in s te a d o f ra p id a d d it io n , which g ives th e

su lfe n y l bromide) gave a h igh y ie ld of b is ( te tr a -0 -a c e ty l-p -D -

g lucopyranosy l) d is u l f id e (2 4 ). I t may be supposed th a t bromine

r e a c ts w ith 19 to g ive th e su lfe n y l bromide 22, which then r e a c tsMw iw rww ith excess 1 -th io g ly c o s id e 19 to g ive th e g lucosy l d is u lf id e 24

and t e r t -b u ty l brom ide. Such a re a c t io n would be f a c i l i t a t e d by

22 + 19 — *- 24 + He^CBrm m Mm m m ^

th e ease o f h e te ro ly s is o f th e C -l-S bond in 19 during a tta c k ofMMth e e le c t ro p h i l ic s u l fu r atom of 22 on th e n u c le o p h ilic s u lfu r

atom of 19. Support fo r t h i s mechanism i s p rov ided by th e observa-MMt io n t h a t , in carbon te t r a c h lo r id e , compound 22 r e a c ts w ith 19 to

MM Mm

g ive th e d is u lf id e 24 in h igh y ie ld , and a v o la t i l e t e r t -b u ty l

d e r iv a tiv e i s produced.

The s u lfe n y l bromide 22 was decomposed ra p id ly by dry e th a n o l,MM "

and th e m ajor p roduct o f re a c tio n a f t e r 0 .5 h r a t 25° was b i s ( t e t r a -

O -ace ty l-p -g -g lucopy ranosy l) d is u lf id e 24j none of th e su lfe n y l

bromide 22 could be d e te c te d . V/ater, a ls o , caused ra p id decomposi

t io n of th e su lfe n y l bromide 22, bu t in t h i s case th e p r in c ip a l

c r y s ta l l in e p ro d u c t, i s o la te d in 59^ y ie ld , was a compound having

th e em p irica l form ula ^28^38^19S2* CorresPonding to a mono-oxide of

th e d is u lf id e 24; compound 24 was ob tained c o n c u rre n tly , in 6$

64

y ie ld . The mono-oxide 30 m igra ted more slow ly th an th e d is u lf id e

on t . l . c . , and was absen t from th e product o f r e a c t io n of th e

su lfe n y l bromide 22 w ith dry e th a n o l. S ep ara tio n of th e mono-oxide

30 from th e d is u l f id e 24 could be e ffe c te d r e a d i ly , because o f th e

extreme low s o l u b i l i t y o f th e form er in co ld e th a n o l. The n .m .r .

s p e c tra of 24 and th e mono-oxide 30 were very c lo s e ly s im i la r , and

d i f f e r e n t n o tic e a b ly only in th e p a t te rn of th e a c e ty l-g ro u p s ig n a ls

a t h igh r e s o lu t io n ; th e two compounds were r e a d i ly d i f f e r e n t ia te d ,

however, by t h e i r i . r . sp e c tra (see F igure 1) and X-ray powder d i f

f r a c t io n p a t te r n s .

O x ida tion of th e d is u l f id e 2£ w ith nj-chloroperoxybenzoic

a c id gave a mono-oxide d e r iv a tiv e id e n t ic a l w ith th a t ob ta ined by

t r e a t i n g th e s u lfe n y l bromide 22 w ith w ater. An excess of th e o x i-

dant d id not appear t o cause o x id a tio n to a more h ig h ly oxygenated

d e r iv a tiv e . Treatm ent o f th e su lfe n y l bromide 22 w ith 95$ e thano l

gave a m ixture o f th e mono-oxide and th e d is u l f id e 24.

The mono-oxide may be fo rm ula ted e i th e r as a s u lfe n ic

anhydride (R-S-O-S-R) o r as a t h io l s u l f in a te [R -S-S (o)-R ]; th e

fo rm u la tio n R-0-S-S-R i s excluded by th e n .m .r . d a ta . By analogy

w ith work on sim ple compounds o f r e la te d s t r u c tu r e ,^ ® th e

(110) E. V inkler and F. KLive'nyi, Acta Chim. Acad. S c i.

Hung., 11, 15 (1957).

(111) E . V ink ler and F. K liv en y i, i b i d . , 22, 345 ( i9 6 0 ) .

(112) J . L. Kice and G. B. L arge, J . Amer. Chem, S o c .,

20 , 4069 (1968).

65

AcOCHAcOCH,,o sO S B r

dry EtOHOAcOAc

AcOAcAcOAc22 Ac

OAcAc

OAc

24AcOCH*

OAcAcO

OAcAcOCH

AcAc

Scheme I I . —Form ation o f b is ( te t r a - 0 - a c e ty l - p - p - g lu c o - pyranosy l) d is u l f id e (2£) and b is ( te tra -O -a c e ty l-p -B -g lu c o p y ra n o sy l) d is u lf id e mono-oxide TSQ) •

t h io l s u l f in a te s t r u c tu r e (30) may be considered th e more p ro b ab le ,

a lthough t h i s su p p o s itio n has not been proved r ig o ro u s ly . A com

pound having s t ru c tu r e (30) should be capable of e x is te n ce in two

d ia s te re o iso m e ric form s. I n v a rio u s p re p a ra tio n s o f th e mono-oxide,

th e crude product had a m eltin g p o in t much low er th a n th a t o f th e

p roduct a f t e r r e c r y s t a l l i z a t i o n from hot e th a n o l. P o s s ib ly , th e

crude p roduct was a d i f f e r e n t s t r u c tu r a l isom er o f th e mono-oxide

o r a m ixture of d ia s te re o iso m e rs o f 30.

A p la u s ib le ro u te fo r th e fo rm ation o f th e mono-oxide ^0

In th e re a c t io n o f th e s u lfe n y l bromide 22 w ith w ater would involve

h y d ro ly s is of one m olecule of 22 t o th e s u lfe n ic a c id , fo llow ed byMfW 9

r e a c t io n o f the l a t t e r w ith a second m olecule of 22 to g ive the

R-S-Br + H20 V " - RSBP . R—S -O n | u “ H B r V v"' H

R - S - B r 10 VR — S " B r

‘“ H B rR— S - > 0I

R—S

t h io l s u l f i n a t e . I n th e r e a c t io n w ith e th a n o l, i t i s conceivable

t h a t th e observed d i s u l f id e 24 may a r i s e by th e r e a c t io n o f a

m olecule o f an e th y l s u lfe n a te w ith a m olecule o f th e su lfe n y l

brom ide, w ith fo rm ation o f e th y l hypobrom ite by su lfu r-o x y g en

67

bond-cleavage, s in c e th e E t-0 bond would not be su s c e p tib le to

R-S-Br+EtOH R-S-OEt — R-S-S-R+EtOBr

a b s tra c tio n of th e Et group by bromide io n . These r a t io n a l iz a t io n s

have no t been proved ex p e rim en ta lly .

G. Extended brom ination o f 1 - th io sugar d e r iv a tiv e s

Brom ination of th e t e r t - b u ty l l- th io -D -g lu c o s id e 19, th e» ■■ ■ ■. — *****

d is u lf id e 24. or th e d is u lf id e mono-oxide 30 in carbon t e t r a -

c h lo rid e fo r an extended p e rio d o f tim e gave te tra -0 -a c e ty l-a .-D -73glucopyranosyl bromide ( l ) . I t had p re v io u s ly been dem onstrated

th a t th e s u lfe n y l bromide 22 and 1-th io-B -D -glucopyranose p e n ta -#W|W 1 —a c e ta te ( l6 ) a ls o formed te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l bromide

when re a c te d w ith an excess of bromine in carbon te t r a c h lo r id e fo r

an extended p e rio d of tim e . A p o s s ib le m echan istic r a t io n a le i s

o u tlin e d in Scheme I .

H. R eaction of te t r a -O -a c e ty l-p - p luco p y ran o sy lsu lfen y l bromide(22) w ith e le c t ro n - r ic h c e n te rs

a . R eaction of 22 w ith a n i l i n e .—The su lfe n y l bromide 22

re a c te d r e a d i ly w ith a n i l in e to g ive the c r y s ta l l in e sulfanam ide

31 in 82$ y ie ld . A t r a c e o f th e d is u l f id e 24 was formed in th e******

re a c t io n m ixture as in d ic a te d by t . l . c . The e lem ental an a ly ses of

th e p roduct e s ta b lis h e d th a t i t had been formed by condensation of

one m olecule of th e amino w ith one m olecule o f s u lfe n y l bromide w ith

th e lo s s o f a m olecule o f hydrogen brom ide. This evidence does not

68

prove th e sulfenam ide s t r u c tu r e , because a tta c k o f th e su lfe n y l

bromide 22 on th e a ry l r in g -p o s i t io n s cannot be excluded. The

n .m .r . s p e c tra p rov ided c le a r con firm ation of th e sulfanam ide

s t r u c tu r e , A one-pro ton s in g le t was observed ( a t YA.76, w ith

chloroform -d as so lv en t) th a t cou ld be a ssig n ed to th e NH p ro to n of

a su lfenam ide, because i t was exchanged slow ly when the sample was

d e u to ra te d . The reg ion fo r a ry l p ro to n s in te g ra te d fo r f iv e p ro to n s

th u s p rov ing th a t s u b s t i tu t io n on th e a ry l nucleus had not taken

p la c e .

r in g p ro to n s on th e sugar m oiety b y 'f i r s t - o r d e r in sp e c tio n (see

T a b le s8 and 'SO, The assignm ents were v e r i f ie d by sp in decoupling .

A s t r ik in g fe a tu re of th e spectrum i s th e h igh f i e ld - p o s i t io n of

th e H -l s ig n a l . Because th e H -l s ig n a l i s s h i f t e d away from th e

H-2, H -3, and H-4 s ig n a ls , i t i s p o s s ib le t o analyze th e l a t t e r

s ig n a ls r e a d i ly . In most o f th e a c e ty la te d d e r iv a tiv e s o f 1 - th io -

p-D -glucopyranose, th e p ro x im ity o f th e H -l s ig n a l t o th o se of H-2,

H-3, and H-4 makes d e ta i le d s p e c t r a l a n a ly s is d i f f i c u l t . ^ j t has

AcOCl-^

OAc

31

The n .m .r . spectrum of 31 was analyzed com pletely fo r th e

69

no t been e s ta b l is h e d whether th e unusual sh ie ld in g o f H-l i s on

in d u c tiv e e f fe c t of th e sulfenam ide group, or whether i t i s th e

e f f e c t o f th e lo c a t io n of H -l in th e sh ie ld in g re g io n of th e n -c lo u d

above or below th e arom atic r in g .

b . R eaction o f th e s u lfe n y l bromide 22 w ith an a c tiv a te d■ ■ ■■ IP * ■ I — ■ i ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ P • n mm m ,m ■ ■■ ■1.11 ■

a ry l d e r iv a t iv e .—The s u lfe n y l bromide 22 was a llow ed to r e a c t in

a carbon te t r a c h lo r id e medium w ith two molar e q u iv a le n ts of N,N-

d im e th y la n ilin e . The l a t t e r was s e le c te d as an a c t iv a te d , arom atic

m olecule th a t r e a d i ly undergoes s u b s t i tu t io n , p r in c ip a l ly a t th e

p a ra p o s i t io n , by e le c t r o p h i l i c re a g e n ts . The m ajor p roduct i s o

l a t e d was, th e g lu co sy l d is u l f id e 2A (y ie ld 62^), a lthough th e

a n tic ip a te d p ro d u c t, 4,-(dim ethylam ino)phenyl t e t r a - O - a c e ty l - l - th io -

p-D -glucopyranoside (^ 2 ), was formed sim u ltan eo u s ly , in low y ie ld .

The s t ru c tu r e o f th e product was apparen t from th e d a ta of e lem ental

a n a ly s is and n.m.r. sp ec tro sco p y ; th e spectrum was amenable to f i r s t -

o rder a n a ly s is o f th e carbohydrate p o r t io n , and th e assignm ents

(se e T ab le s8 and 9 ) were confirm ed by sp in decoup ling . Chemical

co n firm atio n of th e s t ru c tu r e of 32 was ob ta ined by independent

sy n th e s is through coup ling o f te tra -O -a c e ty l-o -D -g lu c o p y ran o sy l

bromide w ith js-d im ethylam inobenzeneth io l, as f i r s t describ ed by

Montgomery, R ichtm yer, and H u d so n .^ The p rocedure was improved

by p rep a rin g th e t h i o l from p,-(dim ethylam ino)phenyl th io cy an a te by

re d u c tio n w ith l i th iu m aluminum hydride in s te a d o f t i n and a c id .

A complex serieB o f secondary re a c t io n s ensued if, after*th e su lfe n y l bromide 22 had been t r e a te d w ith two m olar p o rtio n s

o f H ,N -d im ethy lan iline , th e r e a c t io n m ix ture (presum ably

70

co n ta in in g th e p roduct 32; N ,N -d iraethy lan iline hydrobrom ide; p robably

th e g lu co sy l d is u l f id e 24 ; and, p o s s ib ly o th e r pi’oducts) was heated

f o r 20 min a t a r e l a t i v e ly h igh tem pera tu re (1 0 5 °). F ra c tio n a tio n

o f th e r e a c t io n m ixture gave (see Scheme I I I ) in a d d it io n to

b is ( te tra -O -a c e ty l-p -D -g lu c o p y ra n o sy l) d is u lf id e (2 4 ), 2,-bromo-77

N ,N -d im ethy lan iline (3 3 ), b is(p-d im ethylam inophenyl) d is u l f id e (,34),

te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l bromide ( l ) f and a product

c lo s e ly resem bling th e adduct of 32 i n i t s n .m .r . s p e c tr a l d a ta ,

b u t c o n ta in in g an a d d it io n a l s u lfu r atom; i t was fo rm ulated as p -

(dim ethylem ino)phenyl te tra -O -ace ty l-p -D -g lu co p y ran o sy l d is u lf id e

(3 5 ). These p ro d u cts p ro b ab ly a r i s e by a s e r ie s o f m e ta th e tic a l

re a c t io n s between prim ary re a c t io n p ro d u c ts , and f r e e - r a d ic a l

b rom ination of th e amine by 22 i s a p o ss ib le ro u te to 33. Thewiw *

f a c to r s c o n tro l l in g th e d is t r ib u t io n of th e se p roducts were not

In v e s t ig a te d .

c . R eaction o f th e s u lfe n y l bromide 22 w ith ke tones and" " " ■ ■ ■ ■ ■ ■ ■ ■ i n i i - — — ■ ■ - ■ n i— i a * A * ■ ' ■ « ■ ■■ n ■

ph en o l. —To determ ine w hether the su lfe n y l bromide would r e a c t

w ith e n o liz a b le ke tones by a tta c k o f th e s u lfu r a t th e a -p o s i t io n

t o th e carbonyl group, se p a ra te experim ents were conducted w ith

22 and acetophenone, a c e to n e , and cyclohexanone, r e s p e c t iv e ly .

In each c a se , th e r e a c t io n gave b is ( te tra -0 -a c e ty l* -p -D -g lu c o -

p y ranosy l) d is u l f id e (2£) in h igh y ie ld . P o s s ib le , f r e e - r a d ic a l

brom ination of th e k e to n es p ro v id es a more favo red re a c t io n

pathway th an e le c t r o p h i l i c a t ta c k by s u lfu r on th e e n o lic forms of

th e k e to n e s . The g lu co sy l d is u l f id e 2^. was ob ta ined in h igh

71

NMe,

22 +

AcOCH

AcOOAc

AcOCH.

OAcAcO

OAc24

AcOCH

OAc+

B rAcOOAc

AcOCHj, * / = N T e2

B r

33

Me.

34

AcOCHa / = \ kS - ^ N M ^

Scheme I I I . —High tem pera tu re (105°) re a c t io n o f t e t r a - 0 - a ce ty l-p -D -g lu co p y ran o sy lsu lfen y l bromide (22) and N ,N -dim ethyl- a n i l in e . ”

y ie ld i n th e r e a c t io n between th e s u lfe n y l bromide 22 and pheno l,

and no product o f a tta c k on th e a ry l r in g by s u lfu r was d e te c te d .

I . R eaction o f p e ra c e ty la te d 1 - th io sugars w ith bromine and i s o la t io n o f tra p p in g p ro d u c ts

The n .m .r . s p e c t r a l s tudy of th e brom ination o f 1 - th io sugars

in carbon te t r a c h lo r id e was used as a guide fo r determ ining re a c t io n

tim es i n an a ttem p t to t r a p u n s ta b le su lfe n y l bromide in te rm e d ia te s .

I t was dem onstra ted by th e n .m .r . study th a t b rom ination o f 1 - th io -p -

D-xylopyranose t e t r a a c e t a t e (15 ) o r 1 - th io -a -L -a rab in o p y ran o se t e t r a

a c e ta te (1 4 ) gave immediate fo rm ation of th e corresponding g lycosy l

bromide a t a p robe tem peratu re o f 34-°. Thus, th e re a c t io n m ixture

was coo led to abou t - 10° b e fo re brom ination in an a ttem pt t o r e ta r d

fo rm ation of th e g ly c o sy l brom ide. The u t i l i t y o f t h i s method was

dem onstrated e a r l i e r in th e la rg e s c a le p re p a ra tio n of t e t r a - 0 -

a c e ty l-p -D -g lu co p y ra n o sy lsu lfen y l bromide (22 ) .

1-T hio-p-D -xylopyranose t e t r a a c e ta t e (15) was brom inated a tSilow tem pera tu re and v o l a t i l e r e a c t io n components were im m ediately

removed by e v ap o ra tio n . An excess o f b en zen eth io l was added in an

a ttem p t t o t r a p any tr i-O -a c e ty l-p -D -x y lo p y ra n o sy lsu lfe n y l bromide

(38) p r e s e n t . T . l . c . showed th e p resence of a major component, .

R£ 0 .8 9 , b u t an n .m .r . spectrum o f the crude syrup in chloroform -d

showed more th an one m ajor re a c t io n p ro d u c t. A lo w -f ie ld doublet

was a ss ig n e d to H -l of tri-O -ace ty l-cs-D -xy lopy ranosy l bromide (^ ) ,

and th e In te g ra te d in te n s i t y o f t h i s p ro to n to th e a c e ty l p ro tons

was in a r a t i o o f 1 j1 6 , which in d ic a te d th a t ^ was th e p r in c ip a l

73

re a c tio n p ro d u c t. In an analogous experim ent th e bromide A was

i s o la te d in 61% y ie ld .

Phenyl tr i-O -a ce ty l-p -D -x y lo p y ra n o sy l d is u lf id e (39) was

p re se n t in th e r e a c t io n m ixture and was i s o la te d in 3% y ie ld a f t e r

decom position o f th e x y lo sy l bromide

Trapping o f th e x y lo sy lsu lfe n y l bromide 38 w ith a -to lu e n e -

t h i o l gave an 18% y ie ld o f benzyl tri-O -ace ty l-p -D -x y lo p y ran o sy l

d is u l f id e (AO) is o la te d by column chromatography and c r y s ta l l iz e d

from e th e r —petro leum e th e r .

The s t r u c tu r e s o f th e tra p p in g p roducts 22 an^ £2 were e s~

ta b l is h e d by e lem ental a n a ly s is and n .m .r . s p e c tra l d a ta a t 100 MHz

w ith chloroform -d as so lv e n t (see F igure 2 , and Tables 8 and 9 ) .

Each compound showed a lo w -f ie ld reg io n fo r th e a ry l p ro tons w ith

an In te g ra te d in te n s i ty o f f iv e p ro tons and an a c e ty l reg ion w ith

an in te g ra te d in te n s i ty o f n ine p ro to n s , A tw o-proton s in g le t

was a ssig n ed to th e b e n zy lic CH,. protons fo r AO. The C-5 methylene

groups were analyzed as th e AB p o r tio n o f an ABXX system and th e

h ig h e r - f ie ld q u a r te t was a ss ig n ed to th e a x ia l H-5 in th e Cl (D)

conform ation on th e b a s is o f a la rg e coupling co n stan t = 8 .9 Hz

f o r 39 and 9 .0 Hz fo r AO and th e lo w e r - f ie ld q u a r te t was assigned

t o th e e q u a to r ia l H-5 based on th e sm a lle r coupling c o n s ta n t,

—A ,5s = ô r *22 ôr T his system was analogous

t o th a t re p o rte d f o r l- th lo -p -D -x y lo p y ran o se t e t r a a c e t a t e ^ (!,§)•

T ri-O -ace ty l-a -D -x y lo p y ran o sy l bromide (A) can conceivably

be formed d i r e c t ly by cleavage o f th e sugar to s u l fu r bond or by

way o f tr i-O -a c o ty l-p -D -x y lo p y ra n o sy lsu lfe n y l brom ide. Perhaps

74

SAc S B r

B r ,OAcOAc>Ac CCI CC!

B rAcO AcOAcOOAc)Ac

38

PhCH.SHPhSH

Q SSPh ■O SSCH^Ph

OAc>AcAcO Ac

OAc OAc

39 40

Scheme IV .—Formation o f phenyl tr i-O -a c e ty l-p -D -x y lo pyranosy l d is u lf id e (39) and benzyl tri-O -ace ty l-B -D -x y fo p y ran o sy l d is u l f id e (4 0 ) . “

75

both mechanisms a re o p e ra tiv e . A d e f in i te mechanism cannot be

determ ined from th e experim ental evidence a v a ila b le .

s u i t s s im ila r to th o se encountered in th e fo rm ation o f the phenyl

D -xylosyl d is u lf id e 39. I t -was dem onstrated th a t t r i -O -a c e ty l- p -

L -arab inopyranosy l bromide (3) was formed in high y ie ld , even w ith

b rom ination of 14 a t low tem p era tu re . Phenyl tr i-O -a c e ty l-a -L -

arab inopyranosy l d is u lf id e (4 1 ) was i s o la te d from th e re a c tio n

m ixture in 45& y ie ld . N .m .r. s p e c t r a l da ta showed th e presence

of a compound s im ila r in s t r u c tu r e to 41 and t h i s compound i s probably

Low-temperature brom ination of 1 -th io -a -L -arab in o p y ran o se

t e t r a a c e ta te (14 ) follow ed by tra p p in g w ith b en zen eth io l gave r e -

Br2 ,CCI4

AcC

OAc OAcOAc14 45 3

PhSH

41

76

phenyl 1 -th io -a -L -a rab in o p y ran o s id e t r i a c e t a t e (4-2). R eaction of

excess b en zen e th io l and tr i-O -a c e ty l-p -L -a ra b in o p y ra n o sy l bromide

(3 ) p re s e n t in th e re a c tio n m ixture could account fo r th e presence

of 42.

The s t r u c tu r e o f 41 was e s ta b lis h e d by e lem ental a n a ly s isMMand n .m .r . s p e c t r a l da ta a t 100 MHz fo r a so lu tio n of 41 in

chloroform -d. A wide doublet a t 75 .27 was a ssig n ed to H -l of 41.*■ A/M

The coupling co n stan t of 7 .2 Hz i s in accord w ith th e d ia x ia l

r e la t io n s h ip o f H -l to H-2 in th e Cl (L) conformer fo r 41. The

spectrum showed a ry l and a c e ty l reg ions c o n s is te n t w ith th e assigned

s t r u c tu r e . Q u arte ts a t h ig h e r f i e l d were assigned to H -5 ,51,

however, no a ttem p t was made to d i f f e r e n t i a t e between a x ia l and

e q u a to r ia l p ro to n s due t o th e sm all d iffe re n c e in coupling observed

(see F igu re 3 and Tables 8 and 9 ) .

T . l . c . of th e re a c tio n product o f low -tem perature brom ination

o f 1 -th io -B -D -galac topyranose p e n ta a c e ta te (17) showed th a t incom-ZZ a/m

p le te b rom ination of 17 had occu rred , a lthough th e n .m .r . sp e c tra l

s tu d y of th e brom ination o f 18 a t a probe tem perature of 34° showedMWfo rm ation of te tra -O -a c e ty l-a -D -g a la c to p y ra n o sy l bromide (2) a t a

r a te f a s t e r th an was measurable by th e n .m .r . techn ique a p p lie d .

B rom ination o f 17 a t room tem peratu re follow ed by tra p p in g w ith

b en zen e th io l gave a m ixture of th re e p ro d u c ts , a s in d ic a te d by t . l . c .

One o f th e components corresponded to s t a r t in g m a te r ia l 17 and wasPm**

l e s s in te n se th an th e corresponding component observed fo r th e

brom ination experim ent a t low tem pera tu re . A 60-MHz n .m .r . spec

trum o f a s o lu t io n o f th e crude re a c tio n product in chloroform -d

77

showed th e p resence o f s t a r t i n g m a te r ia l and a b enzeneth io l adduct,

a s in d ic a te d by th e a ry l reg io n p re sen t in th e spectrum . No low-

f i e l d dou b le t was p re se n t t o in d ic a te th e p resence of te tra -O -

ae e ty l-a -D -g a la c to p y ra n o sy l bromide (2) and v e r i f i c a t io n was made

by th e lac k o f decom position of th e product during a p rocess de

s ig n e d to decompose th e r e l a t i v e ly u n s ta b le 2 . A low y ie ld (6%)

o f phenyl te tra -O -a c e ty l-B -D -g a lac to p y ra n o sy l d i s u l f id e (A3) was*“ SI

i s o la t e d c r y s t a l l i n e from th e re a c tio n m ix tu re . S tru c tu re

assignm ent f o r j 3 was based on elem ental a n a ly s is and s p e c tra l d a ta .

A 100 MHz spectrum fo r a chloroform -d s o lu tio n o f A3 showed th e a ry l -

p ro to n s ig n a ls as a c h a r a c te r i s t i c lo w -f ie ld m u lt ip le ! . H-2 and H-A

gave a complex m u lt ip le t , and a q u a r te t a t Â.91 was a ssig n ed to

H-3. A wide dou b le t having a spacing of 10 Hz was a ss ig n ed to H -l.

The wide coup ling i s a t t r ib u te d to th e a x ia l - a x ia l re la t io n s h ip

f o r H -l and H-2 in th e C l-(2 ) conformer fo r A3. A m u lt ip le t a t

T 5 .6 7 -6 .0 6 was a ssig n ed to H-5, 6 , and 6 *. The a c e ty l s ig n a ls were

in acco rd w ith th e s t r u c tu r e o f A3 (see F igure A and Tables 8IWMand 9 ) .

AcOCH2AcO/— Q\ /— \OAc ■

AcOCI-AcO > ~ Q

\ OAc

Ac OCH2

A c O ^ Q\G A c

17 44 43

78

The poor y ie ld of 43 can be a t t r ib u te d to i t s d i f f i c u l ty

in c r y s t a l l i z a t io n except when r e l a t i v e ly p u re . S ep ara tio n o f 43

from th e m ixture o f re a c t io n p ro d u cts was d i f f i c u l t .

B rom ination of 1 -th io -a-D -g lucopy ranose p e n ta a c e ta te (18)

a t a probe tem p era tu re of 34° gave e i th e r te tra -O -a c e ty l-a -D -

g lu co p y ran o sy lsu lfen y l bromide (25) or b is ( te tra -0 -a c e ty l-a ~ D -

glucopyranosy l) d i s u l f id e (26) as evidenced by th e n .m .r . s p e c tra l

d a ta . An attem pt was made to brom inate 18 a t room tem pera tu re and

to t r a p 25. S p e c tra l evidence was ob tained th a t an a ry l tra p p in g - *****product had formed (see F igu re 5)> however th e product could not be

is o la te d p u re . T h ere fo re , i t cannot be s ta te d d e f in i te ly th a t j2§

was a re a c t io n p roduct in th e b rom ination of 1 - th io -a -D -g lu co -

pyranose p e n ta a c e ta te (L8 ) .

B rom ination of 2 ,3 ,4 ,6 - te t r a -O -a c e ty l- l -S -b e n z o y l- l - th io -

p-p-glucopyranose (29 ) a t room tem pera tu re fo llow ed by trap p in g

of th e product w ith b en zen e th io l gave a 295& y ie ld of phenyl t e t r a -

O -acety l-p -D -g lucopyranosy l d is u l f id e (23 ) , id e n t ic a l w ith an 73a u th e n tic sample'-^ by m .p ., n .m .r . d a ta , and X-ray powder d i f f r a c

t io n p a t te r n . Form ation o f 23 as a trap p in g product of te tra -O -

a ce ty l-p -D -g lu co p y ro n o sy lsu lfe n y l bromide (22 ) f u r th e r supported

th e m echan istic r a t io n a le proposed fo r th e fo rm ation o f the s u lfe n y l

bromide 22 (see Scheme I ) . I f th e aglycon i s a c a tio n more s ta b lemm w

th an th e g ly co sy l c a t io n , th e g lu c o sy lsu lfe n y l bromide form s.

However, i f th e aglycon forms a c a tio n l e s s s ta b le th a n th e g ly co sy l

c a t io n , th e n te tra -O -a c e ty l-a -D -g lu c o p y ra n o sy l bromide ( l ) i s th e

79

AcOCH. AcOCH.AcOCH

PhSH

re a c tio n p ro d u c t. This r a t io n a le appears to be t r u e w ith 1 - th io -

p-D -glucose p re c u rso rs as dem onstrated by th e fo rm ation of th e

g lu c o sy lsu lfe n y l bromide 2 2 , i d e n t i f i e d by i s o la t io n of c r y s ta l -

l in e 22 or by tra p p in g w ith e le c t r o n - r ic h reag en ts such as th io l s

or am ines.

The s u lfe n y l bromide 22 was found to be a product of th e

brom ination o f 1 -th io -p -D -g lucopy ranose p e n ta a c e ta te (1 6 ), t e r t -—. mm ~~b u ty l 1 - th io -p -D -g lu c o p y ra n o s id e te tra a c e ta te (1 9 ), and 2 ,3 .4 ,6 -

Z * MM

te tra -O -a c o ty l- l-S -b e n z o y l- l- th io -p -D -g lu c o p y ra n o se (29 ). In each

case extended b rom ina tion , w ith carbon te t r a c h lo r id e as s o lv e n t,

gave te tra -O -a c e ty l-a -p -g lu c o p y ra n o sy l bromide ( l ) .

The brom ination o f phenyl (20) and benzyl 2 ,3 ,4 ,6 - te t r a -O -

a c e ty l- l- th io -p -D -g lu c o p y ra n o s id e (21 ) gave no evidence th a t 22

had form ed. The brom ination o f 21 a p p a re n tly proceeded by way ofM M

th e benzyl p ro to n s o f th e ag lycon . In each case extended brom ina

t io n gave th e g ly co sy l bromide 1 .

Trapping p ro d u cts w ith b en zen e th io l wero ob ta ined from th e

brom ination o f 1 -th io -p -D -xy lopy ranose t e t r a a c o ta te ( l§ ) ,

80

l- th io -a -L -a ra b in o p y ra n o se t e t r a a c e ta te (1 4 ), and 1 -th io -p -D -

g a lac to p y ran o se p e n ta a c e ta te (17)* Form ation of th e s e trap p in g

p ro d u c ts in d ic a te d th e p resence of th e re s p e c tiv e s u lfe n y l brom ides.

T e t r a -0-ace ty l-B -D -g a lac to p y ran o 3y ls u lfe n y l bromide (44) appeared

t o be more s ta b le th an tr i-O -a c e ty l-p -D -x y lo p y ra n o sy lsu lfe n y l

brom ide (38 ) or tr i-O -a c e ty l-a -L -a ra b in o p y ra n o sy lsu lfe n y l bromide

(4 5 ) , as evidenced by th e la c k of form ation o f th e g a la c to sy l

brom ide 2 a t room tem peratu re in th e sh o rt- te rm brom ination of 17.

(113) K. Freudenberg and A. V/olf, B e r . , 60, 232 (1927).

been known f o r many y e a rs and g ives r e l a t i v e ly low y ie ld s o f

J . P h o to ly s is of sugar d im ethylth iocarbam ates

The Freudenberg rearrangem ent'* '^ of sugar x a n th a te s has

rearrangem ent p ro d u c t.H 3 ,1 1 4

CSM e

(114) M. L. Wolfrom and A. B. F o s te r , J . Amer, Chera S o c ., 28, 1399 (1956).

81

Horton and P rih a r sy n th esized various d im ethy lth iocarba-115mates of sugars and P rih a r has dem onstrated by th e rm o ly tic

(115) H. S. P rih a r K .S. t h e s i s , The Ohio S ta te U n iv e rs ity ,

1967.

s tu d ie s on th e dim ethylth iocarbair.ates th a t th e se compounds do not

o f fe r s ig n i f ic a n t advantage over th e x an th a tes fo r rearrangem ent to

g ive a th io - s u b s t i tu te d sugar r in g . I t had been dem onstrated th a t

carbon to s u lfu r bond cleavage occurs®J under p h o to ly tic co n d itio n s

viith carbohydrate m olecules to g ive deoxy su g a rs . I t was a n t i c i

p a te d th a t p h o to ly s is o f sugar N ,N -dim ethylthiocarbam ates might

le a d to a Freudenberg type of rearrangem ent, g iv ing carbohydrate

d e r iv a tiv e s w ith su lfu r a tta c h ed to th e sugar r in g , or g ive a new

p h o to ly tic ro u te to deoxy su g a rs .

a . P rep a ra tio n of d im ethy lth iocarbam ates. —The d im ethyl-

th iocarbam ates were syn thesized accord ing to th e method o f Horton

and P r ih a r . The sugars used fo r th e se p re p a ra tio n s were blocked

so th a t only one f re e OH group was a v a ila b le fo r r e a c t io n w ith N,N-

dim etbylthiocarbarnoyl c h lo r id e . The p h y sic a l d a ta of th e dim ethyl

th iocarbam ates p repared were in reasonab le agreement w ith those

p re v io u s ly re p o rte d (see Table 7 fo r compounds p repared and mode

of c h a ra c te r iz a t io n ) .

b* .P h o to ly sis of th e d im ethylth iocarbam ates 46, 47 , and 4 8 .—" - l i t -it w iw * m m * ’

M ethanolic so lu tio n s of 4 6 , £ 7 , and ^8 wore pbotolyrsed f o r extended

p erio d s of time w ith in te rm it te n t p ro cess in g to e lim in a te polym eric

TABLE 7

DIKETHILTKEO CARBAMATES OF SUGARS

Compound Mode of c h a ra c te r iz a tio n

m.p. [a]jj(CHCl^) o ther

3 -0 -D im ethy lth iocarbam oyl-l,2 : 5 ,6 -d i-O - isopropy lidene-a-D -g lucofuranose U6) 105-106° -62 .6 ° n .m .r .

1 ,6 -Anhydro-A-0 -dim ethylthiocarbam oyl- 2 ,3 -0 - is opr opylidene-p-D-mannopyranose (A7; ~ 136-137° -83° n .m .r.

6-0-D Im ethylthiocarbam oyl-1,2 :3 ,4--d i-0- isopropy lidene-a-D -galactopyranoseU s)MM 90-91° -5 8 .9 ° n .m .r .

83

re s id u e formed* The re a c tio n s were m onitored by n .m .r . and

t . l . c . to determ ine necessary p h o to ly s is times and product forma

t io n . T . l . c . in each experim ent showed th e p resence of an a rra y

o f p ro d u c ts ; however, two major p roducts were p re se n t in each

p h o to ly s is m ix tu re , and were se p a ra ted by column chromatography

and id e n t i f i e d .

P h o to ly s is of 3 -Q -d im e th y lth io ca rb am o y l-l,2 :5 ,6 -d i-0 -

isopropylidene-o .-D -glucofuranose (46) gave a 17? y ie ld o f 3~deoxy-

l , 2 : 5 , 6 - d i - 0 -iso p ropy lidene-a -D -ribo -hexo fu ranose (49) and a 26?

y ie ld o f l ,2 :5 ,6 -d i-0 -iso p ro p y lid e n e -a -D -g lu c o fu ra n o se (jjO).

VJhen th e re a c tio n was re p e a te d , re sp e c tiv e y ie ld s of 22 .5? and

32? were ob ta ined .

~ O C K MeC I ‘2 sOCHr ^ O C N M e , - p o

Y J o * W

J)-CMe2 f Q-CMea q -<

4 6 49 5 0

Compound 50 was id e n t ic a l w ith an a u th e n tic sample by m .p .,

(116) W, L. Glenn, G. S. M eyers, and G. A. G ran t, J . Chem.

S o c ., 2568 (1951).

n .m .r . spectrum , and by X-ray powder d i f f r a c t io n p a tte rn

84

The 3-deoxy-a-B -hexofuranose 49 was p u r i f ie d by d i s t i l -

l a t i o n . The o p t ic a l r o ta t io n of 49 was in good agreement w ith th efWMknown v a lu e ^ , , ^ ^ and th e n .m .r . d a ta (60 MHz) were c o n s is te n t

(117) M. Cerny and J . Pacak, C o lle c t, Czech. Chem.

Commun., 21, 1003 (1956).

(118) E. J . Hedgley, W. G. Overend, and R. A. C. Rennie,

J . Chem. S o c ., 4701 ( 1963) .

119w ith those re p o rte d f o r a carbon te t r a c h lo r id e s o lu t io n of 49.

(119) D. M. Brown and G. H. Jo n es, i b id . . 252 (1967).

A c r y s ta l l in e d e r iv a t iv e , 3 -d e o x y -l,2 -0 -iso p ro p y lid e n e -a -D -rib o -

hexofuranose (5 1 ), was p rep a red by p a r t i a l h y d ro ly s is o f 40 byX18th e procedure o f Hedgley, Overend, and Rennie.

An a u th e n tic sample o f 3 -d e o x y - l,2 :5 ,6 -d i-0 - iso p ro p y lid e n e -

g-D -ribo-hexofuranose (4£) was prepared according to the method of

Brown and J o n e s ^ ^ from 3 -d e o x y -3 -io d o -l,2 :5 ,6 -d i* '0 -iso p ro p y lid e n e -

o -D -g lucofuranose (5 2 ). l ,2 :5 ,6 -D i-0 - is o p ro p y l id e n e -3 -0 -£ - to ly l-

su lfonyl-a-D -glucofurano3 e (5 3 )^ 0 -1 2 2 vas trea ted with hydrazine*

(120) K. Freudenberg and 0 . I v e r s , B e r ., 929 (1922),

(121) D. H orton, J , S . J e w e ll , and H. S. P r ih a r , Can. J .

Chem., £6 , 1580 (1967).

(122) R. J . Abraham, L. D, H a ll , L. Hough, and K, A,

McLaughlan, J . Chem. S o c ., 3699 (1962).

85

t o form 3 -deoxy-3 -h y d ra z in o - l ,2 : 5 , 6 - d i - 0-isopropylidene~a-]D -

a l lo fu ra n o s e (5 4 ) .1^ * 1^ ' R eaction o f 54 w ith io d in e gave

(123) M, L. Wolfrom, J . Bernsmann, and D. Horton, J . Org.

Chem., 27, 4505 (1962).

(124) B. Coxon and L. Hough, J . Chem. S o c ., 1643 (1961).

3 -deoxy-3 - i o d o - l ,2 : 5 , 6 -d i-O -isop ropy lideno -a-D -g luco fu ranose

( 5 2 ) . ^ ^ R eduction of 52 w ith Raney n ic k e l11^ gave 3 -d e o x y - l,2 :5 ,6 -

d l-O -iso p ro p y lid en e-q -D -r ib o -hexofuranose (4 9 ). P a r t ia l a c id

h y d ro ly s is o f 49 gave an a u th e n tic sample o f 3 -deoxy-1 , 2- 0 -

iso p ro p y lidene-q -D -ribo -hoxo fu ranose (51 , H 8 ( see Scheme V)

i d e n t i c a l w ith 51 p repared from 49 by th e p h o to ly s is o f 46 by com-

p a r is o n of m .p ., X-ray powder d i f f r a c t io n p a t te rn and n .m .r .

s p e c t r a .

Cerny and Pacak117 re p o rte d [ c ]18 -3 7 .8 ° (c 0 .635 , e th an o l)

f o r 3 -deoxy-1,2 -0 - isop ropy lideno -a-D -ribo -hexo fu ranose (5 1 ); however,

th e o p t ic a l r o ta t io n fo r t h i s p re p a ra tio n of 51 was [ c ]?3 - 1 2 . 6°+*** JD(c 1 .1 , e th a n o l) and [ a j j*1 -1 9 .0 ° (c 1 .7 , ch lo ro fo rm ).

D e su lfu r iz a tio n o f b is ( l ,2 :5 ,6 -d i-O - iso p ro p y lid e n e -a -D -

g lac o fu ran o se ) d is u lf id e (55) 113 w ith Raney n ic k e l gave l , 2 : 5 ,6 - d l -

O -isop ropy lidene-a-D -ribo -hexo fu ranose (49 ) id e n t ic a l w ith au thon-

^ o p t ic a l r o ta t io n and n .m .r . spectrum . P a r t i a l a c id

h y d ro ly s is o f 49 gave 3~ deoxy-1 ,2 -0 -isopropy lidene-g-D -r ib o -

hexofuranose (51) id e n t ic a l w ith an a u th e n tic sam ple.

P h o to ly s is of a m ethanolic s o lu tio n o f 6 -0 -d im e th y lth io -

c a rb a m o y l- l,2 :3 ,4 “d i-0 -iso p ro p y lid e n e -a -p -g a la c to p y ra n o se (^8 )

86

OCH, M « £ |

OCH OCHMezC(

OCH*

nh2n h 2

CMe*

53

HOCK

HOCH

OCH

NH 0 X M e 2 NH,

CHCL,

"2

54

.O C K M eC / I 2

2 NOCH

^ - £ 2 1N H C I ^

H 0 X M e 2

0 /C M e 2

Ra[Ny H

CMe,

51 4 9

Scheme V.— P re p a ra tio n o f 3 -deoxv-l 2-Z « m n -t*. dene-a-D -ribo -hexofu ranose (49) and 3 - d ^ x v - l 2 n ,dJ " ^ i s °Pr J P y l i - c-D -rlho-hexofaranosa ( 51) i f a k i l n ^ / • 2- < K « l > r w ‘l i d ™ -

87

gave a 15% y ie ld o f 6 -d eo x y -l,2 :3 ,4 .-d i-0 -i3 o p ro p y lid en e-a -D -

ga lac topyranose (56) and a 35.5% y ie ld of 1 ,2 :3 ,4-“d i“0 - iso p ro p y li-

dene-a-D -gal a c t opyranos o (5 7 ).

sQ p f i N M e ,

MeC cT ^

48 56.

CHpHo ) — Q

+ W\eC-\o

57O - 0 M e 2.

H ; *a c e to n eTsCI>

p y rid in e

6 -D eoxy-l,2 :3 ,4 --d i-Q -isop ropy lidene-a -D -galac topy ranose (56)

c ry s ta l l iz e d n ea t and was id e n t ic a l w ith an a u th e n tic sample p re

p ared accord ing to Freudenberg and R a s c h ig .^ ^

(125) K. Freudenberg and K. R aschig, B e r ., 60, 1633 (1927).

8 8

The n .m .r . spectrum o f an acetone-d^ s o lu tio n of 56 was id e n t ic a l

to th a t described by Cone and Hough.

(126) C. Cone and L, Hough, Carbohyd. R e s ., 1 , 1 (1965)*

Compound 57, a sy ru p , was p u r i f ie d by d i s t i l l a t i o n and was

id e n t i f i e d as l , 2 : 5 , 6-d i-Q -iso p ro p y lid en e-a -D -g a lac to p y ran o se (57)127 128 126by comparison o f th e o p t ic a l r o ta t io n ’ and n .m .r . spectrum

(127) 0 . T, Schm idt, Methods Carbohyd. Chem., 2 , 324

(1963).

(128) D. H orton, M, Na3cadate, and J . M. J , T ronchet,

Carbohyd. R es ., 2 , 56 (1968).

w ith th o se p re v io u s ly r e p o r te d . The syrupy product was c h a ra c te r iz e d

a s i t s 6 -£ - to lu e n e su lfo n a te (58) and th e m .p ., X -ray powder d i f f r a c -

t io n p a t te r n , and n .m .r . spectrum o f a chloroform -d s o lu tio n of

58 were in good agreement w ith l i t e r a t u r e v a lu e s .

P h o to ly s is o f a m ethanolic s o lu tio n of l,6 -a n h y d ro -4 -0 -

d im ethylth iocarbam oyl-2 ,3-0-isopropylidene-p-D -m annopyranose (47)

gave a 19$ y ie ld of a p roduct fo rm ula ted as l , 6 -anhydro**4 “deoxy-

2 .3 -Q -isopropy lidene-B -D -ly x o -hexopvranose ( 59) and a 17$ y ie ld

o f l,6 -anhydro -2 ,3 -0 -isop ropy lidene-p -D -m annopyranose (6 0 ). The

r e a c t io n was rep e a te d and gave 26$ and 29$ of 59 and 60 re sp e c -ww wwt i v e ly .

Form ulation of 59 as th e 4**deo^ sugar was based on

89

CMe.

47

hrMeOH

ChL— O

59 60

elem ental a n a ly s i s , n .m .r . s p e c t r a l d a ta (see T ables 10 and 11 ) ,

and by analogy w ith th e fo rego ing p h o to ly s is r e a c t io n s .

The l,6 -anbydro -2 ,3 -0 -ispp ropy lidene-p -D -m annopyranose

(60) was i d e n t i c a l w ith an a u th e n tic s a m p le .^ 9 j l3 0

(129) A. E. Knauf, R. M. Hann, and C. S. Hudson, J . Amer.

Chem. S o c ., 6 ^ , UU7 (1941).

(130) D. H orton and J . S. Je w e ll, Carbohyd. R e s ., 2 , 251

(1966).

c . P h o to ly s is o f 3 -d eo x y -3 -io d o -l,2 :5 » 6 ~ d i-0 - iso p ro p y lid en e"

a-D-g lu co fu ran o se ( 52) . —B inkley and B in k le y ^ showed th a t p h o to ly s is

of a prim ary io d o - s u b s t i tu te d sugar in m ethanol gave a deoxy sugar’

in h ig h y ie ld . I t was a n t ic ip a te d th a t p h o to ly s is of a secondary

io do -sugar would g ive s im ila r r e s u l t s and t h i s was dem onstrated by

p h o to ly s is o f a m ethano lic s o lu t io n o f 3 -d e o x y -3 - io d o - l ,2 :5 ,6 -d i-

O -isop ropy lideno-a-D -g luco fu ranose (5 2 ). T . l . c . o f th e crude

p h o to ly s is r e a c t io n p ro d u ct rev e a le d th e presence o f th re e components.

90

One of th e m ajor components, R . 0 .8 5 , was I s o la te d in 3%% y ie ld by

column chrom atography and was id e n t i f i e d as 3 - d e o x y -l,2 :5 ,6 -d i-O -

.OCH M eC ;' I

^ OCHhv, MeOH Wj

NaOH+

o th e r p ro d u c ts

52 49

iso p ro p y lid en e-g -D -r ib o -hexoCuranose (49) by comparison of n .m .r .

s p e c t r a l d a ta and o p t ic a l r o ta t io n w ith those o f a known sam ple.

Compound 1$ v,as f u r th e r c h a ra c te r iz e d by conversion in to a known

c r y s ta l l in e d e r iv a t iv e , 3 -d eo x y -lf2 -O iso p ro p y lid en e -a -D -r ib o -

D -glucofuranose (52) i s thought t o proceed by hom olysis o f the C -I

bond fo llow ed by a b s tr a c t io n o f a p ro ton from th e s o lv e n t, m ethanol,

as was d e sc rib e d f o r fo rm ation of a deoxy sugar from 6-deoxy-6-iodo-

P h o to ly s is o f d im ethy lth iocarbam ates o f v a rio u s p ro te c te d

sugars in m ethanol s o lu t io n thus a ffo rd s a p re p a ra tiv e method f o r

deoxy su g a rs . A lthough th e y ie ld s a re no t h igh th e a lc o h o l s id e -

p ro d u ct can bo r e - e s t e r i f i e d and recy c led in th e p h o to ly s is , and

th e n e t y ie ld s compare fav o rab ly w ith those th a t can be achieved by

conven tiona l m u lt i- s to p ro u te s . The re a c t io n appears t o p roceed by

hexofuranose117’118 (51)V w #

P h o to ly s is o f 3 -d eo x y -3 - io d o -l,2 :5 J6 -d i-0 -iso p ro p y lid e n e “Ci-

1 ,2 :3 ,4 “d i - 0 - i s opropy lidene-a-D -galactopyranose

rearrangem ent of S-dim ethylcarbam oyl d e r iv a tiv e s o f th e c o r re s

ponding th io sugars and subsequent C-S s c is s io n to g ive a deoxy

ROH — ROCNMe^,-S n

ORSCNM ez RH

R = s u g a r

sugar; a concu rren t p ro cess invo lves sim ple cleavage o f th e d im ethy l-

thiocarbam oyl group to g ive th e a lc o h o l. These r a t io n a l iz a t io n s

have not been proved ex p erim en ta lly .

K. N .m .r. s p e c t r a l study o f deoxy sugars

a . 3 "D ao x y -l,2 :5 ,6 -d i-0 -iso p ro p y lid en e-c :-D -rib o -h ex o -

furanose (4-9).—Broun and J o n e s ^ ^ re p o rte d 60 KHz n .m .r . d a ta■ MMf o r a carbon te t r a c h lo r id e s o lu t io n o f 4-9. The spectrum fo r aMM *

chloroform -d s o lu t io n of 49 showed s ig n a ls o f H -l, H-2, and H-3a, 3b#

c le a r ly ; however, th e H-4, H-5, and H-6a, 6b s ig n a ls were

observed a s m u lt ip le ts . The H -l s ig n a l was a doub le t w ith 2 =

4 .0 Hz; th a t o f H-2 uas a t r i p l e t which in d ic a te d la c k of coupling

between one of th e H-3 p ro to n s and H-2. I r r a d ia t io n o f the h ig h -

f i e l d H-3 m u lt ip le t r e s u l te d in p e r tu rb a tio n o f th e H-2 s ig n a l , and

th e l o u - f ie ld H-3 m u lt ip le t . I r r a d ia t io n of th e H-2 s ig n a l r e s u l te d

in c o lla p se o f th e H -l doub le t to a s in g le t and p e r tu rb a tio n o f

th e h ig h - f ie ld H-3 s ig n a l; however, no change was observed in th e

* a , lo w -f ie ld s ig n a l; b , h ig h - f ie ld s ig n a l .

92

lo w - f ie ld H-3 m u l t ip le t . No advantage was gained 'by th e use of

aco tone-d^ as s o lv e n t fo r 49 . Uhen benzene-d^ was used a s s o l

v e n t, th e H-4 s ig n a l was observed as a m u tl ip le t , T6.69-6.90*

Spin decoup ling o f th e lo w e r - f ie ld H-3 q u a r te t (T7.82) caused

p e r tu rb a tio n o f th e H-4 s ig n a l . The h ig h - f ie ld H-3 s ig n a l was

s h i f t e d under th e s ig n a ls o f th e iso p ro p y lid en e p ro to n s (see

F igu re 6 .

b . 6“D e o x y -l,2 i3 » 4 -d i-0 -iso p ro p y lid e n e -a -D-galactopyranose

(5 6 ) .—Cone and H ough^^ re p o rte d 60 MHz n .m .r . d a ta f o r an

ace to n o -d / s o lu t io n o f 56. P ro tons were a ssig n ed on a f i r s t - o r d e r

b a s i s f o r a 100 MHz spectrum o f an acetone-d^ s o lu tio n o f £6 . The

C-6 m ethyl p ro to n s gave a doub let a t '*'8.84 w ith an in te g ra te d i n

t e n s i t y of th r e e p ro to n s in d ic a t in g th a t th e H-6 pro tons were

e q u iv a le n t and were coupled w ith H-5. A dd itiona l narrow s p l i t t i n g

(" 1 .0 Hz) was observed fo r th e p r in c ip a l q u a r te ts of H-2 and H-3.131-135The a d d it io n a l co u p lin g i s p robab ly long-range coupling ^

(131) D. R. D av is, R. P. L u tz , and J . D, R o b e rts , J .

Amer. Chem. S o c ., 83 . 246 (1961).

(132) J . Keinwald and A. Lewis, i b id . . 2769 (1961).

(133) L . D. H a ll and L. Hough, P roc . Chem. S o c ., 382 (1962).

(134) K. Heyns, J . Weyer, and H. P au lsen , B e r ., 28 , 327

(1965).

(135) D. H orton and J . S. J e w e ll , Carbohyd. R e s ., £ ,

149 (1967).

93

a lthough no a ttem p t -was made to a ss ig n t h i s coupling to s p e c if ic

p ro to n s . The 100 MHz n .m .r . d a ta fo r a chloroform -d so lu tio n was

s im ila r ly f i r s t - o r d e r w ith th e excep tion th a t a s l i g h t overlap of■

H-4 and H-5 occurred and a d d it io n a l sm all coupling (presumably

long -range coupling) was observed fo r th e p r in c ip a l q u a r te ts of

H-2 and H-3. A ll p ro ton assignm ents were v e r i f ie d by sp in -decoup ling

experim ents (see Tables 10 and 11 fo r fu r th e r s p e c tr a l d e t a i l s ) .

c . l,6 -A nhydro -4 -deoxy-2 ,3 -0“l3opropy lidene-p -D -lyxo-

hexopyranose (5 9 ) .—The 100 MHz n .m .r , spectrum in e i th e r c h lo ro

form -d o r ace to n e -d . was complex. For a chloroform -d s o lu t io n ofo ”H -l was observed as a broadened d o u b le t. In a d d itio n to coupling

o f H -l w ith H-2, th e p o s s ib i l i ty e x is ts f o r long-range coupling w ith

H-3, H-5, and p o ss ib ly H-6 ( e x o ) .^ 5 The s ig n a l fo r H-2 i s a sharp

q u a r te t w ith = 3 .0 Hz and ^ = 5-9 Hz, A m u lt ip le t , T5 . 4 I -

5 .70 was a ss ig n ed to H-6a# and H-3. The h ig h - f ie ld m u lt ip le ts ,

T7.70 and 7 .92 were a ssigned to H-4a* and H-4b*. H-5 was a ssig n ed

to a m u l t ip le t , T 6 .25 . The p r in c ip a l s t ru c tu re o f th e m u lt ip le t ap

peared as a t r i p l e t . The a d d it io n a l s p l i t t i n g o f th e t r i p l e t can be

a t t r ib u te d to long-range coupling w ith H -l and H-3. A q u a r te t a t T

5.94 w ith ^ = 0 , J^ a ^ = 6 .4 was assigned to H-6b and an

a d d it io n a l coupling was p re se n t o f 1 .5 Hz w ith e i th e r H -l or H-4.

Spin decoupling was an a id in a ssig n m en t.o f p ro to n s . I r r a d ia t io n

o f th e s ig n a l assigned to H-2 caused c o lla p se of th e H -l s ig n a l to

a s in g le t and p e r tu rb a tio n of th e m u ltip le t assigned to H-3 and H-6a.

£The lo w -f ie ld H-6 p ro to n i s in d ic a te d by a and th e

h ig h - f ie ld H-6 p ro to n is in d ic a te d by b.

94

I r r a d i a t i o n of th e s ig n a l a ssigned to H-4.a and H-4b r e s u l te d in p e r

tu rb a t io n o f th e H-3 and H-6a m u lt ip le t in a d d it io n to narrow ing th e

m u lt ip le t a ssig n ed to H-5. I r r a d ia t io n of th e H-5 m u lt ip le t r e s u l te d

i n p o s s ib le p e r tu rb a tio n o f th e H-3 and H-6a m u lt ip le t , c o llap se of

th e H-6b s ig n a l , and c o lla p se o f th e H-4a and H-4b s ig n a ls to q u a r

t e t s , = 5 .0 Hz, = 2 .8 Hz, and J^ a ^ = 15 .0 Hz. Assign

ments were d i f f i c u l t to make due to th e complex n a tu re o f the

spectrum (see F igure 8 and Tables 30 and 11 f o r f u r th e r d e t a i l s ) ,

d . 3 -D3oxy~3 ‘‘io d o -d l- 0 - i 3op ro p y lid en e-a -D-g lucofuranose

( 5 2 ) .—A 100 MHz spectrum of 52 w ith chloroform -d as so lv e n t showed

th e H -l, 2 , and 3 s ig n a ls as d o u b le ts a t T 4.08 , 4 .99 and 5.58

r e s p e c t iv e ly . Brown and Jones‘S assigned a h ig h - f ie ld m u lt ip le t ,

T 6 .85 , t o H-5 fo r a carbon te t r a c h lo r id e s o lu t io n of ^ 2 . I r r a d ia

t io n of th e h ig h - f ie ld m u lt ip le t c o llap sed th e doub let assigned

t o H-3 t o a s in g l e t . I r r a d ia t io n o f th e H-3 s ig n a l caused p e r tu rb a

t io n of th e h ig h - f ie ld m u lt ip le t . I r r a d ia t io n of th e H -l doub let

c o lla p se d th e H-2 doub let to a s in g l e t . I r r a d ia t io n o f th e H-2

d oub le t c o lla p se d th e H -l doub let t o a s in g le t and no change was

observed fo r the H-3 s ig n a l , which showed th a t th e H-2 and H-3

p ro to n s a re t r a n s d isposed and th a t Jg 3 i s approx im ate ly equal to

z e ro . Thus, th e g luco c o n fig u ra tio n assig n ed by Brown and Jones^"^

was re a ff irm e d . A m u lt ip le t , T 5 .83- 6 .0 8 , was ass ig n ed to H-5, 6 ,

and 6 1.

EXPERIMENTAL - PART A

G eneral methods. —Evaporations were perform ed under dimin

ish e d p re s su re (~10 mm) on a r o ta r y ev ap o ra to r. S p e c if ic ro ta t io n s

were measured in e i th e r a 1-dm tu b e (Perkin-E lm er 141 p h o to e le c tr ic

p o la rim e te r) o r a 2-dm tube (Rudolph manual p o la r im e te r ) . M elting

p o in ts were determ ined w ith a Thomas Hoover Unimelt a p p a ra tu s . I . r .

s p e c tra were measured w ith a Perkin-E lm er "In fraco rd " in f r a re d

spectropho tom eter. N .m .r. s p e c tra were measured a t 60 or 100 14Hz

w ith Varian A-60 or HA-100 n .m .r . sp ec tro m ete rs . Chemical s h i f t s

r e f e r to an in te r n a l s tan d ard o f te tra m e th y ls i la n e (IMS) (t=10.00)

f o r o rgan ic so lu tio n s and sodium 2 ,2 -d im e th y l-2 -s ila p e n ta n e -5 -

su lfo n a te (D3S) (T=10.00) fo r aqueous s o lu t io n s . Spin-decoupling

experim ents were perform ed w ith th e HA-100 in strum en t o p e ra tin g in

th e frequency-sw eep mode. U lt r a v io le t sp e c tra were measured w ith a

Bausch and Lomb "S pectron ic 505" reco rd in g sp ec tro m ete r. M icro-

an a ly ses were determ ined by W. N. Rond. X-ray powder d i f f r a c t io n

d a ta g ive in te rp la n a r sp a c in g s , 2 , fo r CuKa r a d ia t io n . The camera

d iam eter was 114.59 mm. R e la tiv e i n t e n s i t i e s were e stim ated v is u a l ly :

a , m oderate; s , s tro n g ; v , ve ry ; w, weak. The s tro n g e s t l in e s a re

numbered ( l , s t r o n g e s t ) ; double numbers in d ic a te approxim ately

equal i n t e n s i t i e s . Thin la y e r chrom atography ( t . l . c . ) was perform ed

w ith Desaga equipment and S i l i c a Gel G (E. Merck, D arm stadt, Germany)

95

96

a c t iv a te d a t 120° as th e ad so rb en t, 3:1 dichlorom ethane—e th e r as

developer (u n less s p e c if ie d o therw ise) and s u l f u r ic a c id as th e in d i

c a to r . Column chromatography was perform ed w ith s i l i c a g e l No. 7734

(0 .0 5 -0 .2 mm) o f E. Merck AG, Darm stadt, Germany w ith 1 g o f th e mix

tu re t o be se p a ra te d p e r 30 g o f ad so rb en t. Columns were packed by

a llow ing a s lu r r y of th e adsorbent in th e e lu en t to s e t t l e under

g ra v i ty . The e lu e n t was 3*1 d ichlorom ethane—e th e r (so lv en t A) or

9 :1 d ichlorom ethane—e th e r (so lv e n t B). Solvent A i s th e e lu e n t of

choice where no s p e c i f ic e lu e n t i s in d ic a te d . Petroleum e th e r usedo

in r e c r y s ta l l i z a t io n s was a f r a c t io n having a b o i l in g range 60-110 .

P re p a ra tio n of t e t r a -O-a c e ty l- f t-D-g lucopyranosyl bromide ( l ) . —

Compound 1 was p repared e s s e n t ia l ly accord ing to th e procedure of

B arczai-M artos and Korosy^® as d esc rib ed by L em ieux .^ A cetic an

hydride (400 ml) was cooled ('“10°) and 70% p e rc h lo r ic ac id (2 .4 ml)

was added dropw ise. The cooled s o lu tio n was brought to room

tem peratu re and D-glucose (100 g , 55.5 mmoles) was added to

th e v ig o ro u s ly s t i r r e d s o lu tio n over a p e rio d of 30 min as to

c o n tro l th e tem pera tu re between 30 and 4 0 ° . The re a c tio n m ixture

was cooled below 20° and red phosphorus (32 g) was added to th e

r e a c t io n m ixture fo llow ed by th e dropwise a d d itio n o f bromine (62 m l,

193.4 g) over a p e rio d o f 1 h r . Water (36 ml) was added dropwise

over a 30 min p e r io d so as to m ain tain th e re a c tio n tem perature be

low 2 0 ° . The m echanical s t i r r e r was removed from th e re a c tio n

m ixture and th e re a c t io n Diixture was removed from th e ice b a th and

allcw ed to rem ain u n d is tu rb ed a t room tem peratu re f o r a pEriod of

2 h r . D ichlorom ethane (300 ml) was added to th e m ix tu re , which

97

was th en f i l t e r e d th rough C e li te to remove excess phosphorus. The

f i l t r a t e was added w ith c au tio n to ic e and w ater (*“700 g ) . The

o rg an ic phase was s e p a ra te d and washed su c ce ss iv e ly w ith an ic e -c o ld ,

s a tu ra te d s o lu t io n o f sodium hydrogen carbonate ('“600 m l) , and w ater

(~600 m l). The d r i e d (magnesium s u l f a te ) s o lu tio n was evaporated

to g ive a c r y s t a l l i n e , w hite mass. The crude p roduct was d ig es te d

w ith 250 ml o f e th e r , warmed on a steam b a th , and r e f r ig e r a te d

o v e rn ig h t. The p ro d u c t was c o l le c te d in th re e c ry s ta l c ro p s , y ie ld

182.8 g , 44*5 mmoles (8 0 ^ ), m.p. 88-89°, [ o ] ^ +198° (c 1 .2 , ch lo ro

form) [ l i t . ^ m.p. 8 8 -8 9 ° , +198° (c 2 ,“ch lo ro fo rm )]. The

n .m .r . d a ta fo r a ch lo ro fo rm -d s o lu t io n co incided w ith th a t rep o rte d92p re v io u s ly by H orton and Turner.

P re p a ra tio n o f t e t r a -O-a c e ty l -a-D -g a lac to p y ran o sy l bromide

. —A cetic anhydride was coo led to “ 10° and 2 .4 ml of a 7C$ s o lu

t io n o f p e rc h lo r ic a c id was added dropwise w ith s t i r r i n g . The

coo led s o lu t io n was brought to room tem perature and D -galactose

(100 g , 55 .5 mmoles) was added to th e re a c tio n m ixture over a 30 min

p e rio d in o rd e r t o m a in ta in th e tem perature between 30-40°. The

re a c t io n m ix ture was t r e a te d w ith re d phosphorus (32 g ) , bromine

(62 m l, 1 9 3 .4 g ) , and then w ater (36 m l) , by th e procedure used

in th e fo reg o in g experim ent and th e work-up was e s s e n t ia l ly th e

same as t h a t d e sc r ib e d fo r 1 , however, a syrup was ob ta ined in s te a d

o f a c r y s ta l l in e p ro d u c t. The syrup would not c r y s t a l l i z e from

e th e r or e th e r —p etro leu m e th e r . A em ail amount ('■'1 g) of th e

syrup was passed down a column o f s i l i c a g e l w ith so lv e n t A as

98

e lu e n t. F ra c tio n s th a t con ta ined th e product were c o lle c te d and

evapo ra ted to g ive a c o lo r le s s sy ru p . The syrup was d isso lv e d in a

few ml of e th e r (~2 ml) and r e f r ig e r a te d o v e rn ig h t. White need les

formed and th e y were added to an e th e r so lu tio n o f th e m ajor syrupy

p ro d u c t. The p roduct c r y s ta l l i z e d overn igh t as a w hite c r y s ta l l in e

m ass, y i e ld 90 .0 g , 21 .9 mmoles (40$), m.p. 82 -83°, Ca ] ^ +212.9°

(c 2 .9 , chloroform ) [ l i t . 93 m, p , 83-84°, [a ]^ ° +215° (c=l , ch lo ro

fo rm )]. The n .m .r . spectrum o f 2 in a ch loroform -d s o lu t io n wasM92c o n s is te n t w ith th a t rep o rte d p re v io u s ly .

The f i l t r a t e was evapo ra ted to a syrup and th e syrup was r e

d isso lv e d in e th e r and seeded w ith c ry s ta l l in e 2 . The s o lu t io n was

r e f r ig e r a te d , but fu r th e r c r y s t a l l i z a t io n d id no t occur. The e th e r

s o lu t io n was re -e v ap o ra ted to a sy ru p , 108.4 g , 2 6 .4 mmoles (48$).

P re p a ra tio n o f tr i-0 -n c e ty l-8 -L -a ra b in o p y ra n o sy l bromide ( 3 ) .—■ 1 1 ! ■ . ■ ■ ■ ■ .1 I P I I . , I T, H +— I . I ■ I - I I - . . . . ts t

A cetic anhydride (300 ml) was cooled to about 20° and 1 .8 ml of 70$

p e rc h lo r ic a c id was added dropw ise. The re a c t io n so lu tio n waB

s t i r r e d and L -arab inose (75 .0 g , 50.0 mmoles) was added over a

30 min p e rio d and th e tem pera tu re was no t allow ed to exceed 30°.

The re a c t io n m ixture was t r e a te d w ith re d phosphorus (22 .5 g ) , bromine

(52 m l, 162.2 g ) , and w ater (27 ml) by th e procedure used f o r th e

p re p a ra tio n o f te tra -O -a c e ty l-c -D -g lu co p y ra n o sy l bromide ( l ) and

th e work-up was th e same a s d e sc rib e d fo r ( l ) . The dichlorom ethane

e x tr a c t was evaporated to g ive a c rude , c r y s t a l l i n e p ro d u c t. The

crude p roduct was d i lu te d w ith e th e r (400 m l) ,warmed to e f f e c t s o lu

t i o n , and d i lu te d w ith petro leum o th e r (50 m l). The p roduct

99

c r y s ta l l i z e d a f t e r r e f r ig e r a t io n overn igh t to g ive 3 as f in e w hite

n e e d le s , y ie ld 84 .7 g , 2 5 .0 mmoles (50$), m.p. 138-140°, [ ° ] ^ +278.9

(c 2 .1 , chloroform ) [ l i t . 9/1 m .p. 139°, +283.6° ( in ch lo ro fo rm )].

The n .m .r . d a ta fo r a ch loroform -d s o lu tio n were c o n s is te n t w ith92th o se re p o r te d p re v io u s ly .

P re p a ra tio n of tr i-O -a c e ty l-f t-D -xylopyranosy l bromide ( £ ) .—

The method used f o r th e p re p a ra tio n of ^ was e s s e n t ia l ly t h a t of

B arczai-M artos and Korb'sy9^ as d esc rib ed by Weygand.9 -* A cetic

anhydride was coo led to 10° and 70$ p e rc h lo r ic a c id (2 .4 ml) was

added to th e s t i r r e d , coo led s o lu tio n fo llow ed by D-xylose (100 g ,

6 6 .6 mmoles) a t a r a te such th a t th e re a c t io n tem pera tu re d id not

exceed 40° . Rad phosphorus (32 g ) , bromine (62 m l, 193 g) » and

w ater (36 ml) were added to th e cooled s o lu t io n as d e sc rib ed fo r

th e p re p a ra tio n o f 1 . The work-up was th e same as d e sc rib e d p re v i-

ously fo r 1 and a d ichlorom ethane s o lu tio n o f th e product was

ev apo ra ted to a sy ru p . The syrup was d i lu te d w ith e th e r (200 ml)

and r e f r ig e r a te d o v e rn ig h t. A w hite mass o f need les formed and was

f i l t e r e d , y ie ld 105.2 g , 31 .0 mmoles (4 7 $ ), m.p. 101-102°,

[ct]jp +211° (c 1 .2 , chloroform ) [ l i t . 95 m .p. 102°, [a]j-° +272°

(a 2 .5 , chloroform ) and l i t . 9^ m .p. 102°, [ n ] j^ +212.2° (c, 2 .5 ,

ch lo ro fo rm )]. An n .m .r . spectrum of th e p roduct in a chloroform -d

s o lu t io n was id e n t ic a l w ith th a t rep o rte d by Horton and T u rner.9^

P re p a ra tio n of t r i -O -a c e ty l - a -jj-xy lopyranosy l c h lo rid e ( j ) . - -

Compound was p repared e s s e n t ia l l y accord ing to th e method of

Hudson and Johnson ,9^ To D-xylose (100.0 g , 66 .6 mmoles) was

added a c e ty l c h lo r id e (410 m l, 454 g) and a c a ta ly t i c p o r t io n of

100

f r e s h ly fu sed z inc c h lo r id e . The r e a c t io n m ix ture was re f lu x e d u n t i l

d is s o lu t io n occurred (about 2 h r ) . The s o lu t io n was co o led , d i lu te d

w ith dichlorom ethane (300 m l) , and poured onto about 1 kg o f ic e

and w a te r. The o rgan ic phase was se p a ra te d and washed w ith a s a tu

ra te d s o lu t io n o f sodium hydrogen carbonate u n t i l th e o rgan ic phase

was n e u tr a l . The organ ic phase was washed w ith w ater (200 m l) ,

d r ie d (magnesium s u l f a t e ) , and evapo ra ted to a l ig h t-y e llo w sy rup .

The syrup was d isso lv e d in e th e r (150 ml) and d i lu te d w ith petro leum

e th e r (50 m l). The s o lu t io n was r e f r ig e r a te d overn igh t to g ive

w hite n e e d le s , in two c r y s ta l c ro p s , y ie ld 9 0 .9 g , 3 0 .8 mmoles (/&%),

m.p. 101-102°, [a ]18 +171 . 4° (£ 2 .4 , chloroform ) [ l i t . 97 m.p. 95-97°,

[a ]^ 9+ l65° (c. 12 , c h lo ro fo rm )]. N .m .r. d a ta (60 MHz, CDCl^) i

73.72 (one-pro ton d o u b le t, g 3 .7 Hz, H - l ) , 7 $ ,4 4 (one-p ro ton

t r i p l e t , J£ 3 ^ 3 ^ 10 Hz, H -3 ), T4 , 69-5 .21 (tw o-pro ton m u lt ip le t ,

H-2 and H-4.) , T5 . 61-6 .32 (tw o-pro ton m u l t ip le t , H-5, 5 ' ) , 7 7 .8 8 ,

7 .95 ( th re e -a n d s ix -p ro to n s i n g l e t s , OAc).

P re p a ra tio n o f 3 ,4 . ,6 - t r i -0 -a c e ty l-2 -0 - tr ic h lo ro a c e ty l-p -D -

g lucopyranosy l c h lo r id e (6 ) . —The method used fo r th e p re p a ra tio n■ " ■ 1 1 ■■■■ *■ — ■ 1 1 - ■o f & was e s s e n t ia l l y th a t adap ted by Lemieux and Howard9** from th e

o r ig in a l p rocedure o f B r ig l . 100 F in e ly powdered p e n ta -0 -a c e ty l-p -

D-glucopyranose (7 , 78.0 g , 200 mmoles, m .p. 129-131°, P fa n s t ie h l

L a b o ra to r ie s , I n c . , Waukegan, I l l i n o i s ) was mixed w ith 177 g of

powdered phosphorus p e n ta c h lo r id e , and carbon te t r a c h lo r id e (40 ml)

was added to th e r e a c t io n m ix tu re . The r e a c t io n v e sse l was equipped

w ith a condenser and dry ing tu b e and th e m ixture was re f lu x e d fo r

101

5 hr a t a tem p era tu re o f 120° ( o i l b a th ) . The r e s u l t in g lig h t-y e llo w

so lu t io n was evaporated under d im inished p re ssu re (w ater a s p ira to r )

u n t i l th e b a th tem pera tu re had r is e n to 85°. The syrup was d isso lv e d

in anhydrous e th e r (160 ml) and r e f r ig e r a te d overn igh t a t -15°» The

c r y s ta l l in e p r e c ip i t a te was b a re ly v i s ib le on th e f la s k bottom . The

c o ld e th e re a l s o lu t io n was shaken v ig o ro u sly p e r io d ic a l ly over a two

day p e r io d . A c r y s ta l l in e mass was observed on th e f la s k bottom and

was c o lle c te d in two c ry s ta l c ro p s , y ie ld 21 ,3 g , 4 5 .3 mmoles

(2 2 .7 ^ ), m.p. 129-132°, ( l i t . ^ m .p.132-138°). The product was r e

c ry s ta l l i z e d tw ice from e th e r to g ive f in e , w hite n e e d le s , m.p. 140-

141°, 1>]30 +8 . 49° (c 1 .15 chloroform ) [ l i t . 100 m .p. 142° and l i t . "“ O q

m .p. 140-142 , [a ] jj +8 .9 (c 1 . 4 , c h lo ro fo rm )]. N .m .r. d a ta (100

MHz, CDCl^): T4 . 4 8 -4 .9 4 (fo u r-p ro to n m u ltip le t (H -l, 2 ,3 ,4 ) ,

T6.6 (one-proton q u a r t e t , J , 4 .9 Hz, H-6 low f i e l d ) , T6.82 (one-p ,b ap ro to n q u a r te t , J ^ 6 2 .5 Hz, J$ a 6b 2 .5 Hz, H-6b h igh f i e l d ) , T7 . 8 9 ,

7 .9 7 , and 7.99 ( th re e -p ro to n s in g l e t s , OAc).

The experim ent was rep e a te d s e v e ra l tim es w ith th e co n d itio n s

and amounts o f s t a r t i n g m a te r ia l and rea g en ts rem aining th e same as

i n th e p rev ious experim ent. The y ie ld d id not improve when 7 was

p u r i f ie d by r e c r y s ta l l i z a t io n from e th an o l to g ive m .p. 132° nor

d id th e y ie ld improve when ev ap o ra tio n tim e a t 85° was extended to

1 h r . The y ie ld s ranged from 12.5 g t o 22.5 g and were m ostly near

th e form er v a lu e . In a l l a ttem p ts to p rep a re 6 , s e v e ra l days o f

coo ling a t -15° w ith in te r m i t te n t shaking was re q u ire d fo r c r y s ta l

l i z a t i o n to occur.

102

P re p a ra tio n of 3 , 4 , 6 - t r i -O-a c e ty l-p -D-glucopyranosyl

c h lo rid e ( 8 ) .—The method used fo r th e p re p a ra tio n of 8 was th a t98

d escrib ed by Lemieux and Howard, Anhydrous e th e r (200 ml) was

s a tu ra te d a t room tem perature w ith anhydrous ammonia. The s o lu tio n

was cooled to 0 ° and f i n e ly powdered 3 ,4 ,6 - t r i - 0 - a c e ty l - 2 - 0 - t r i -

ch lo roacety l-p -D -g lucopyranosy l c h lo r id e (6 , 1 0 .0 g , 21.3 mmoles)

was added to th e cooled s o lu t io n . The m ixture was shaken v ig o ro u sly

fo r about 20 min a t room tem peratu re and a t no tim e was complete98d is s o lu tio n observed as d esc rib ed by Lemieux and Howard. The

re a c tio n m ixture was cooled fo r 5 min in ic e and th e white c ry s ta l -98

l in e re s id u e was c o lle c te d to y ie ld 6 .8 g , m.p. 129-134-° [ l i t .

y ie ld 6 .7 g , m.p. 156-158°, +29° (c , 1 , c h lo ro fo rm )]. The

w h ite , c r y s t a l l in e re s id u e was sw irle d in chloroform (50 ml) and

th e in so lu b le re s id u e was f i l t e r e d o f f . The f i l t r a t e was evaporated

to a c r y s ta l l in e re s id u e and re d is so lv e d in chloroform . This p ro

cedure was rep ea ted fo u r tim es and th e r e s u l ta n t re s id u e was c r y s ta l

l iz e d from e th e r to y ie ld 8, 2 .5 g , 7 .7 mmoles (36$ ), as w hite

n e e d le s , m .p. 152-154°, [ a ] ^ +26.3° (c 1 .4 9 , ch lo ro fo rm ).

P re p a ra tio n of 2 - ( 2 )3 ,4 ,6 - t e t r a -0 -ace ty l-p -D -g lu co p y ran o sy l)-

2 -th iopseudourea hydrobromide ( 9 ) .—The method used fo r th e p rep a ra

t io n o f 9 was according to th e g en era l method o f fierny and c o -w o rk e rs .^

T etra-O -ace ty l-a -D -g lucopyranosy l bromide ( l , 164 g , 399 mmoles) was

d isso lv ed in warm acetone (300 ml) and th io u re a (30 ,5 g , 401 mmoles)

was added to th e s o lu t io n . The r e a c t io n m ixture was re f lu x e d fo r

15 min and s o l id began to form in th e so lu tio n . The re a c t io n m ixture

103

appeared to be com pletely s o l id w ith c ry s ta ls a f te r re f lu x in g fo r

an a d d itio n a l 15 min. The s o l id was d igested w ith an a d d it io n a l

75 ml o f acetone and r e f r ig e r a te d o v e rn ig h t. The y ie ld of 9 a s a

w hite s o l id was 148,7 g , 305 mmoles (76^). A sm all p o r t io n o f the

s o l id (20 g) was re f lu x e d in acetone (100 ml) and f i l t e r e d to give

9 a s w hite n e e d le s , m .p. 204°, [o]n^ -8 .6 5 ° (c 2 .0 8 , w ater) [ l i t , ^*W JJ

m.p. 178° from ace to n e , l i t . ^ m.p. 205° from iso p ro p y l a lc o h o l,

[a ] jp - 7 . 6° (c 1 . 4 4 3 , w a te r) , and l i t . ^ m.p. 192° from e th a n o l,

-8 ,7 2 ° (c 5 .102, w a te r ) ] . An attem pt was made to o b ta in the

n .m .r . spectrum w ith deuterium oxide as so lv en t and DSS as an i n

te r n a l s ta n d a rd , however th e compound was not so lu b le .

P re p a ra tio n o f 2 - ( 2 t3 ,4 ,6 - t e t r a -Q-a c e ty l- f l-D -g a la c to -

p y ra n o sy l)-2 -th iopseudou rea hydrobromide (10 ) . —Compound 10 was" - - r - -i . ..j- •' *' i MW

A 6prepared e s s e n t ia l ly acco rd ing to th e method of Bonner and Kahn

except acetone was used as so lv e n t in s te a d o f iso p ro p y l a lc o h o l.

C ry s ta ll in e te tra -O -a c e ty l-a -D -g a la c to p y ra n o sy l bromide (88 .5 g ,

215 mmoles) was d isso lv e d in acetone (300 ml) and th io u re a (16 .6 g ,

218 mmoles) was added to th e s o lu t io n . The re a c t io n m ixture was

re flu x e d fo r 40 rain when s o l id p roduct began to re a p p e a r . The re a c

t io n m ixture was d i lu te d w ith petro leum e th e r to opalescence and

r e f r ig e r a te d overn igh t t o g ive a s o l id mass o f c r y s t a l s , y ie ld

91 .8 g , 188 mmoles (8 7 ^ ), m.p. 161-163°. A 10-g p o r t io n of th e

product was re f lu x e d in acetone fo r an a d d it io n a l 1 h r and allow ed

to s ta n d a t room tem p era tu re . The w h ite , c r y s t a l l in e product gave

m.p, 16 9 .5 ° , +16.9° (c 1 . 4 6 , e th an o l) [ l i t . ^ m .p. 169 . 5°

a f t e r fo u r c r y s ta l l i z a t io n s from iso p ro p y l a lc o h o l, [ c ] ^ +1 6 . 0 °

104

(c 1 .5 6 0 , e th a n o l) ] . N .m .r. d a ta (100 MHz, deuterium o x id e):

T4 . 39- 4.77 ( fo u r-p ro to n m u lt ip le t , H -l, 2 , 3 , 4-), T-5.45-5.25 1( th re e -p ro to n m u lt ip le t , H-5, 6 , 6 1) , T 7.79 , 7 .8 6 , 7 .9 1 , and 7 .92

( th re e -p ro to n s in g l e t s , OAc).

The re a c t io n was rep e a te d w ith syrupy te t r a -O -a c e ty l- a -

D -ga lactopyranosy l bromide (2 , 108.4 g , 264 mmoles) and th io u re a

(20 .1 g , 264 mmoles). The y ie ld of c r y s ta l l in e 10 was 89 .1 g ,

183 mmoles (69$).

P re p a ra tio n o f 2 -(2 ,3 ,4 --b r i-0 -a c e ty l-a -L -a ra b in o p y ra n o sy l)-

2 -th io p seu d o u rea hydrobromide ( l l ) . —Compound 11 was p repared■■■■■■ ■ — i ..■■■■ - — . ■■39e s s e n t ia l l y acco rd ing to Horton and co-w orkers. A m ix ture of

tr i-O -a c e ty l-p -L -a ra b in o p y ra n o sy l bromide (84 .0 g , 248 mmoles) was

d is so lv e d in warm acetone (300 ml) and th io u re a (1 9 .0 g , 249 mmoles)

was added to th e s o lu t io n . The m ixture was re f lu x e d and th e product

began to c r y s t a l l i z e out o f s o lu t io n a f t e r 15 min. The m ixture was

re f lu x e d fo r an a d d it io n a l 15 min and th e s o lu tio n was coo led to

room te m p e ra tu re . Petroleum e th e r (50 ml) was added and th e m ixture

was r e f r ig e r a te d o v e rn ig h t. The product c r y s ta l l i z e d as f in e w hite

n e e d le s , y i e l d 8 3 .1 g , 200 mmoles, 81$, m .p. 174-175°, +6 . 8°

(c 1 .6 3 , w ate r) [ l i t . 39 m.p. 169-171°, [a]21 +8 . 8 ° (c 1 .3 ," w a te r ) ] .

N .m .r. d a ta (100 MHz, deuterium oxide s o lu t io n ) : T4.44~4.79 ( fo u r-

p ro to n m u l t ip le t , H -l, 2 , 3 , 4 ) , T5.76 (one-p ro ton q u a r te t ,

3 .2 Hz, J ^ a ^ 13 .0 Hz, H-5a low f i e l d ) , T7 .9 7 (one-pro ton q u a r te t ,

^4 , 5b ^ z > H-5b h ig h f i e l d ) , T 7.84 , 7 .8 5 , and 7 .9 4 ( th re e -p ro to n

s i n g le t s , OAc).

1 0 5

P re p a ra tio n o f 2 - ( 2 ,3 , 4 - t r i - 0 - a c e ty l- f t-g - :xylopyrano3y l ) -

2 - th io p 3eudourea hydrobromido (1 2 ) .—Compound 12 was p repared

e s s e n t ia l ly according to th e procedure of S tan£k, S in d lero v a ,

and £ e r n ^ .^ An acetone s o lu tio n of (30 ml) 2 , 3 , 4-**tri-0 - a c e ty l-

a-D -xylopyranosyl bromide (104 E, 307 mmoles) and th io u re a (23.4- E,

307 mmoles) was re f lu x e d 15 min and s o l id p roduct formed in th e

r e a c t io n m ix tu re . The re a c tio n m ixture was re f lu x e d an a d d itio n a l

30 min and th e s o l id mass was d i lu te d w ith acetone (100 ml) and

r e f r ig e r a te d o v e rn ig h t. White c ry s ta ls were c o lle c te d in two

c r y s ta l c ro p s , y ie ld 105.1 g , 253 mmoles, 82%. A 10-g p o r tio n of

th e p roduct was re f lu x e d in acetone (100 ml) and f i l t e r e d from warm

a ce to n e . The c ry s ta l s had m .p. 173°, -3 6 .0 (c 1 .3 , w ater)

[ l i t . ^ m .p, 176-178°, [c-]p -7 1 .0 ° (c 0 .2 7 , e th a n o l-w a te r , 1 :1 ) .

N .m .r. d a ta (100 MHz, deuterium o x id e): T4..26 (one-p ro ton d o u b le t,

—1 2 Y4-.68-5.13 ( th re e -p ro to n m u lt ip le t , H-2, 3 , 4-),

T5.60 (one-pro ton q u a r te t , J . e 3 .6 Hz, J_ 12 .3 Hz, H-5a low

f i e l d ) , 76 .17 (one-p ro ton q u a r te t , ^ 6 .0 Hz, H-5b h igh f i e l d ) ,

T 7.85 , 7 .8 7 , and 7 .89 ( th re e -p ro to n s in g le t s , OAc).

P re p a ra tio n o f 2 - ( 2 ,3 ,4 - - t r i - 0 -a c e ty l-p -D -xy lopyranosy l)-

2 -th iopseudou rea hydroch lo ride (1 3 ).--T h e method used f o r p rep a ra

t io n o f 13 was t h a t o f Bonner and K a h n ,^ however acetone was used

a s so lv e n t in s te a d of iso p ro p y l a lc o h o l. T ri-O -ace ty l-a -D -x y lo -

py ranosy l c h lo rid e (jj, 8 5 .6 g , 290 mmoles) was d isso lv e d in warm

acetone (200 ml) and th io u re a (2 2 .1 g , 290 mmoles) was added to

th e s o lu t io n . The m ix ture was re f lu x e d fo r 0 ,5 h r and th e re a c tio n

106

m ixture appeared as a w hite s o l id mass. Another 250 ml of acetone

was added and th e re a c t io n m ix ture was re f lu x e d an a d d it io n a l 1 .5 h r .

The re a c t io n m ix ture was coo led , d i lu te d w ith petro leum e th e r (50 m l),

and r e f r ig e r a te d to g ive f l u f f y need les in th re e c r y s ta l c ro p s ,

y ie ld 7 6 .6 g , 207 mmoles (71%), m .p. 163-165°. The product (5 g)

was re f lu x e d in acetone (500 ml) fo r 6 .5 h r . The p roduct d id not

d is s o lv e and was f i l t e r e d from th e hot ace tone s o lu t io n to g ive m.p.

181°, [ a j j p -8 9 .2 ° (c 2 .6 , w ater) [ l i t / 6 m.p. 181°, [ a ]^5 -7 1 .5 °

(c 0 .5 8 7 , e th a n o l) ] ; X^Br 5.69 (OAc), ~ 3 .2 (b ro a d ) , 6 .01 pm *“ max(am idinium )^;X ® t8 H 214. nm ( 6 6000); n .m .r . d a ta (100 MHz,

maxdeuterium o x id e ): TA.26 (one-p ro ton d o u b le t, J 5 .0 Hz, H -l,

1,2

T 4.66-5 .16 ( th re e -p ro to n m u lt ip le t , H-2, 3 , 4 ) , ^5 .59 (one-p ro ton

q u a r t e t , J ^ 5a 3 .9 Hz, 12 .3 Hz, H-5a low f i e l d ) , 76 .17 (one-

p ro to n q u a r te t , ^ 6 .1 Hz, H~5b high f i e l d ) , T 7 .85 , 7 .8 6 , and

7 .88 ( th re e -p ro to n sin g le ts* OAc). X -ray powder d i f f r a c t io n d a ta :

16 .66 w, 8 .8 8 s ( 1 ,1 ) , 7 .89 s (1 ,1 ) , 6 .30 vw, 5.89 w, 5.57 w, 5.30

s (2) , 4 .9 0 s ( 3 ) , 4 .56 m, 4 .29 m, 3 .8 6 s ( 5 ,5 ) , 3 .6 9 s ( 5 ,5 ) ,

3 ;53 m, 3 .29 s ( 4 ) .

A nal. C alcd . fo r C^H ^ClhÔ yS; C, 38 .87 ; H, 5 .16 ;

C l, 9 .5 6 ; N, 7 .5 6 ; S , 8 .6 5 . Found: G, 38 .75 ; H, 5 .1 7 ; C l, 9 .7 3 ;

N, 7 .6 4 ; S , 8 .8 9 .

P reparation o f 1 -th io -p -D -g lu cop yran ose p en ta a ceta te (1 6 ) .—

The g en era l procedure o f Cerny and co -w o rk ers^ was e s s e n t ia l ly

fo llo w e d . Sodium hydrogen s u l f i t e (35 .3 g) was d is so lv e d in water

(300 ml) and the s o lu t io n was heated to 85°. To th e s o lu t io n was

added 2 -(2 ,3 ,4 ,6 -te tr a -0 -a c e ty l-p -D -g lu c o p y r a n o sy l) -2 -th io p se u d o u r e a

107

hydrobromide (9 , 127 £ , 261 mmoles) fo llow ed by carbon te t r a c h lo r id e

(300 m l). The heterogeneous s o lu t io n was re f lu x e d 30 min and

cooled to room tem p era tu re . The organ ic la y e r was se p a ra te d and

th e aqueous la y e r was e x tra c te d tw ice w ith 100 -ml p o r tio n s o f c a r

bon te t r a c h lo r id e . The combined organ ic e x tr a c t was washed w ith

w ater (300 m l) , d r ie d (magnesium s u l f a t e ) , and evaporated to a

sy rup . The syrup was d isso lv e d in a m ixture of p y rid in e (200 ml)

and a c e t ic anhydride (175 ml) and r e f r ig e r a te d o v e rn ig h t. The

s o lu tio n was poured onto ic e and w ater (about 1000 g) w ith vigorous

s t i r r i n g . Vfhite c r y s ta l s formed and were c o lle c te d a f t e r 1 h r . The

c ry s ta l s were washed w ith w ater (200 m l), d r ie d in a i r , and r e

c r y s ta l l i z e d from e th an o l to g ive 16 as w hite n e e d le s , y ie ld 8 6 .0 g ,

212 mmoles (8 1 ^ ), m .p. 118- 119° , Ca ]^8 +10° (° chloroform )

[ l i t .43 m .p. 120° , +1 2 .4 ° (c 5 j te tra c h lo rd e th a n e and l i t . ^

m .p. 119-120° +10 .5° (c 0 .6 , c h lo ro fo rm )]. The n .m .r . d a ta

(100 MHz, CDCl^) were c o n s is te n t w ith th o se p re v io u s ly r e p o r t e d .^

l-T h io -p -D-g a lac topy ranose p o n ta a c e ta te (17) from 2 - ( 2 ,3 - 4 ,6 -

t e t r a -0 -a c e ty l - p -D -g a lac to p y ran o sy l)-2 -th io p se u d o u re a hydrobrom ide. —

Sodium hydrogen s u l f i t e (40 g) was d isso lv e d in w ater (200 ml) and

th e s o lu tio n was h e a ted to 85°. To th e s o lu t io n was added 2 - ( 2 ,3 ,4 ,6 -

t e t r a - 0 -a c e ty l-p -D -g a la c to p y ra n o s y l) -2 -th io p seu d o u rea hydrobromide

(1 0 , 120 g , 246> mmoles) fo llow ed by a d d it io n o f carbon te t r a c h lo r id e

(300 m l). The r e a c t io n c o n d itio n s and work-up were th e same as

d esc rib ed i n th e fo reg o in g experim ent. The y ie ld o f w h ite , coarse

need les was 81 .5 g , 201 mmoles, 82%, m.p. 114- 115° +30 .1°

108

(c 2 .1 6 ; chloroform ) [ l i t . ^ ^ m.p. 115-116°, C11] ^ +31*3 (c

c h lo ro fo rm )]. The n .m .r . d a ta (100 MHz, CDCl^) were c o n s is te n t

19w ith th o se p re v io u s ly re p o rte d .

P re p a ra tio n o f 1 - th io - c -L -arabinopyranose t e t r a a c e ta te

(14-).—Compound 14 was p repared from 2 - ( 2 ,3 ,4 - t r i - 0 - a c e ty l - a - L -fWM *******------------------------------------- -a rab in o p y ran o sy l)-2 -th io p seu d o u rea hydrobromide (11, 7 3 .0 g , 176

39mmoles) by th e method d escrib ed by Horton and co-w orkers. J The

method was e s s e n t ia l ly th a t d e sc rib ed f o r th e p re p a ra tio n of 16

from 9 . The a c e ty la te d m ixture d id no t c r y s t a l l i z e when poured#wonto ic e and w ater ("1000 g ) . The syrupy p roduct adhered to th e

s id e s o f th e f la s k and th e aqueous so lu tio n was decan ted . The

syrup was d isso lv e d in dichlorom ethane (200 ml) and th e o rganic

s o lu t io n was washed w ith w ater (100 m l), aqueous sodium hydrogen

carbonate (100 m l), d r ie d (magnesium s u l f a t e ) , and evaporated to

a sy rup . The syrup was d i s t i l l e d tw ice from 100-ml p o rtio n s o f

to lu e n e and tw ice from 100-ml p o r tio n s o f carbon te t r a c h lo r id e .

The r e s u l t in g syrup was d isso lv e d in e th a n o l, seeded , and r e f r i g e r

a te d o v e rn ig h t. White n e e d le - l ik e c ry s ta l s o f 14 were c o lle c te d in

two c ro p s , y ie ld 25 .3 g, 76 mmoles (43*), m.p. 77-78°, [ a ] D +33.3°

(c 1 .7 , chloroform ) [ l i t . 39 m .p. 8 1 .5 -8 2 ° , [a ]^ ° +39.4° (c 2 .2 ,

c h lo ro fo rm )]. The n .m .r . d a ta (100 MHz, CDCl^T were c o n s is te n t w ith

th o se p re v io u s ly r e p o r te d .39

P re p a ra tio n o f l - t h i o - p - D-jcylopyranose te t r a a c e ta t e ( l ^ ) .

From 2 - ( 2 , 3 ,4 - t r i - 0 -a c e ty l-p -p -xy lop yran osy l)-2 -th iop seu d ou rea

hydrobromide (1 2 ) .—Compound 15 was prepared from (81 .0 g , 195

mmoles) by the method d escribed fo r the p rep aration o f

109

1-th io-p -D -g lucopyranose p e n ta a c e ta te (16) from i t s corresponding

th iopseudourea hydrobromide (9)» The a c e ty la te d m ixture d id not

c r y s ta l l i z e when poured onto ic e and w ater (~1000 g) and th e work-up

d escrib ed in th e fo rego ing experim ent was used . The c ry s ta l l in e

y ie ld of lj> was 21,5 g , 64 mmoles (335°)• The p roduct had m.p.

99-100° and [&]]) -7 .0 ° (c 1 .1 , chloroform ) [ l i t . ^ m.p. 99°,

[a]j*^ -6 .8 8 ° (chloroform ) and l i t . . ^ m.p, 103°, Ca ] ^ - 7 .7 (c 1 .4 ,

ch lo ro fo rm )]. The n .m .r . d a ta (100 KHz, CDCl^) were th e same as

p rev io u s ly re p o r te d .39

B, From 2 - ( 2 ,3 t4 - t r i - 0 -a c e ty l- f l-D-x y lo p y ran o sy l)-2 -

th iopseudourea hyd roch lo ride (1 3 ) .—Compound 13 (70 .0 g , 189 mmoles)

when t r e a te d e s s e n t ia l ly as describ ed in th e fo rego ing experim ent

gave 15 (39 .9 g , 119 mmoles, 63%) as w h ite , s to u t n e e d le s , m.p.

99-100° a f t e r one r e c r y s ta l l i z a t io n from e th a n o l.

P re p a ra tio n of 1 -th io -a-D -g lucopyranose p e n ta a c e ta te (1 8 ) .—^ ■ - - ............. ■ I - w 1 ■ ■ * 1 > ■ I ■ 1 ■ ■ ■ — — — — — — A M W

The method used f o r th e p re p a ra tio n of 18 was e s s e n t ia l ly th a t of

M, S akata , M. Haga, S. Tejim a, and M. A k a g i.^ ' To an acetone so lu

t io n (50 ml) o f crude 3 ,4 ,6 -tr i-O -a c e ty l-p -D -g lu c o p y ra n o sy l ch lo rid e

(5 , 6 .2 g , 19 .1 mmoles, m .p. 129-134°) uas added potassium th io la c e -

t a t e (2 ,16 g , 19.1 mmoles) and th e m ixture was re flu x e d fo r 5 min.

The p r e c ip i ta te o f potassium c h lo rid e was f i l t e r e d o f f and th e

acetone f i l t r a t e was evaporated to a syrup* The syrup was d isso lv e d

in p y rid in e (20 m l), a c e t ic anhydride (15 ml) was added to th e s o lu

t io n , and th e s o lu tio n was k ep t overn igh t a t room tem pera tu re . The

s o lu t io n was poured onto ic e and w ater ("500 g) and s t i r r e d fo r

1 h r . The aqueous so lu tio n was decanted and th e rem aining syrup

110

•gas d isso lv e d in d ichlorom ethane (100 m l). The organ ic s o lu tio n

was washed w ith a s a tu ra te d s o lu t io n of sodium hydrogen carbonate

(100 m l), w ater (100 m l) , d r ie d (magnesium s u l f a t e ) , and evaporated

to a sy rup . The syrup was evaporated tw ice from 100-ml p o r tio n s of

to lu e n e , and tw ice from 100-ml p o r tio n s o f carbon te t r a c h lo r id e .

T . l . c . o f th e syrupy p roduct rev ea led th re e components, 0 .86

(m ajo r), 0 .7 3 , and 0 .54 (very m inor). The syrup was c ry s ta l l iz e d

from e th an o l to g ive f l u f f y , n e e d le - l ik e c ry s ta ls th a t were d i f f i

c u l t to f i l t e r , y i e l d 2 .5 g , m .p. 102-105°. T . l . c . o f th e c r y s ta l l in e

p roduct and th e f i l t r a t e rev e a le d th e same th re e components d esc rib ed

f o r th e crude syrupy p ro d u c t. R e c ry s ta l l iz a t io n from e th an o l gave

n e e d le - l ik e c r y s ta l s , m .p. 105-108°. The re a c t io n p roduct was sub

je c te d to column chromatography w ith s i l i c a g e l as th e adsorben t and

so lv e n t A as e lu e n t . The s e p a ra tio n was m onitored by t . l . c . and th e

f r a c t io n s th a t con ta ined th e component having R , 0 .86 were combined,

evaporated to a sy ru p , and c ry s ta l l i z e d from e th a n o l to g ive f lu f f y ,

white n e ed le s . The y ie ld of c r y s ta l l in e 18 was 2 .193 g, 5 .4 mmoles

(2 8 .3 $ ), m .p. 125°, +135° (c 1 .1 2 , chloroform ) [ l i t . ^ m.p.

125°, M f +135° (c 1 .0 , chloroform ) and l i t . '* 2 m .p. 126-127°

[tt]gO +120.2° (c 0 .416 , c h lo ro fo rm )]. N .m .r. d a ta (100 MHz, CDCl^):

73 .76 (apparen t t r i p l e t , H -l, spacing - 2 .1 Hz), 7 ^ .6 8 -5 .0 3 (m u lti-*p l o t , H-2, 3 , 4 ) , 7 5 .7 0 , 5*95 ( q u a r te ts , H-6a and H-6b, low- and

h ig h - f ie ld r e s p e c t iv e ly , J ^ 6a 4 .0 Hz, J ^ 6h 2 .0 H z), 75 .9 2 -6 .1 4

(m u lt ip le t overlapp ing H-6b, H -5), T7 .5 8 ( s in g le t , SAc), T 7.94,

7 .98 ( th re e - and n in e -p ro to n s i n g l e t s , OAc): The H -l s ig n a l a t

60 MHz was an apparen t q u a r te t a t 73 .76 w ith sp ac in g s o f - 1 .2 Hz;

Ill

(100 MHz, benzene-d^): 7 3 .A9 (d o u b le t, H -l, A .7 H z), TA.36-

A.86 (m u lt ip le t , H-2, 3 , A), '•'5.68 (q u a r te t , H-6a, J 5 j6a A.8 Hz),

1*5.88-6.13 (m u lt ip le t , H-6b, H-5) 7 8 .1 7 , 8 .2 6 , and 8 .36 ( s in g le t s ,

th r e e - , n in e - , and th re e -p ro to n s , a c e ty l methyl p ro to n s ) . X-ray

powder d i f f r a c t io n d a ta : 1 2 .5A vw, 9 .AO s ( l ) , 7 .19 vw, 5.AA s (2 ,2 ) ,

5.09 s (2 ,2 ) , A.69 m, A.AO m, A.15 m, 3 .58 m, 3.AA s (3) , 3.29 w,

3 .12 m, 2 .99 w.

A cid -cata lyzed e q u il ib ra t io n of p e n ta -O-a c e ty l -p -D-g luco-

pyranose (7 ) i n t h io l a c t i c a c id w ith z in c c h lo r id e . —F resh ly fu sed

z in c c h lo rid e (5 g) was added to anhydrous e th e r (25 m l). The

f la s k was stoppered and th e suspension was s t i r r e d a t room tem pera

tu r e u n t i l th e s o l id was evenly d isp e rse d on th e bottom o f the f la s k ,

T hio lecdic a c id (15 ml) and pen ta-O -acety l-p -D -g lucopyranose (^ ,

10 .0 g , 25 .6 mmoles) (P fa n s t ie h l L a b o ra to r ie s , I n c . , Waukegan, 111 .)

were added to th e r e a c t io n m ixture and s t i r r i n g was con tinued fo r

16 h r a t room tem p era tu re . Carbon te t r a c h lo r id e (25 ml) was added

and th e so lv e n t was removed under vacuum. The r e s u l t in g crude ,

syrupy re a c tio n product was d i lu te d w ith w ater (100 ml) and carbon

te t r a c h lo r id e (100 ml) and f i l t e r e d . The re s id u e was washed w ith

carbon te t r a c h lo r id e (50 ml) and th e o rganic phase was se p a ra ted from

th e aqueous phase and washed w ith two 100-ml p o r tio n s o f an aqueous

s o lu t io n o f sodium hydrogen ca rb o n a te , w ater (100 m l), and d ried

(magnesium s u l f a t e ) , and evaporated to a dark yellow sy ru p . An n .m .r .

spectrum (60 MHz) of a s o lu t io n o f th e syrup in chloroform -d showed

only th e p resence of 1 -th io -p -D -g lucopyranose p e n ta a c e ta te (16)■“*» mm *and no low f i e l d s ig n a l , T 3 .76 , f o r th e anomerlc p ro to n o f

112

1 -th io -a -D -g lucopy ranose (1 8 ). The syrup was c r y s ta l l i z e d from

e th a n o l to give th e th io a c e ta te 16 in th re e c ry s ta l c ro p s , y ie ld2^ Q

9 .6 g , 2 3 .6 mmoles (92^), m.p. 117-118 , Ca ]j) +9 .5 (c 1 .1 ,

chloroform ) [ l i t . ^ m.p. 120°, [ o ] ^ +12.A° Tc 5, t e t r a c h lo ro -

e thane and l i t . ^ m .p. 119-120°, [ * 0 ^ +10 .5° (c 0 .6 , ch lo ro fo rm )].

The n .m .r . s p e c t r a l da ta (100 MHz, CDCl^) corresponded to th a t39p re v io u s ly re p o rte d fo r 1 -th io -p -D -g lucopyranose p e n ta a c e ta te (16 ).* WM

P re p a ra tio n of benzy l 2 , 3 ,4 ,6 - t e t r a - Q-a c e ty l - l - t h io - p -D-

g lucopyranoside (2 1 ) .—T his compound was p repared acco rd ing to the

method d escrib ed by Horton and c o -w o rk ers .-^ T etra -O -ace ty l-c -D -

g lucopyranosy l bromide (100 g , 2£0 mmoles) was d isso lv e d in 320 ml

o f warm a b so lu te e thano l and th e e th an o l s o lu t io n was added to a

s o lu t io n o f a - to lu e n e th io l (30 ml, 24-0 mmoles) in 3 N e th a n o lic

po tassium hydroxide (80 m l) . The m ix ture was shaken f o r 5 h r a t

room tem p era tu re , co n cen tra ted to a sy ru p , and d isso lv e d in 170 ml

o f a c e t ic anhydride co n ta in in g 10 g o f sodium a c e ta te . The s o lu

t io n was re f lu x e d and poured onto ic e and w ater (-1000 g) and s t i r r e d

f o r 2 h r . C ry s ta l l iz a t io n d id no t occur and the aqueous s o lu t io n was

d ecan ted . The syrupy re s id u e was d is so lv e d in d ichlorom ethane (200

ml) and th e o rgan ic s o lu t io n was washed w ith two 100-ml p o r tio n s o f

a s a tu ra te d s o lu t io n of sodium hydrogen ca rb o n a te , w ater (100 m l),

d r ie d (magnesium s u l f a t e ) , and re -e v a p o ra te d to a sy ru p . The syrup

was c r y s ta l l i z e d from m ethanol to g ive 21 as w hite n e e d le s , c o lle c te d

in two c r y s ta l c ro p s , y ie ld 6 0 .1 g , 132. mmoles, (5550, m .p. 97-99°,

r ° ]p ^ -88° (c 1 .5 , chloroform ) [ l i t . ^ m.p. 100-101°, -94°

(c 0 .6 , chloroform ) and l i t . ^ 7 m .p. 98°, -9 3 .1 °

113

( 1 ,1 ,2 , 2 - te t r a c h lo r e th a n e ) ] . The n .m .r . d a ta (60 MHz, CDCl^)39were c o n s is te n t w ith those re p o rte d p re v io u s ly . T . l . c . o f the

f i l t r a t e showed th e presence o f a m ajor component, R . 0 . 88 , which

corresponded to th e p ro d u c t, however f u r th e r c r y s ta l l i z a t io n d id

no t o ccu r.

P re p a ra t io n o f phenyl 2 ,3 ,4 ,6 - t e t r a -Q -a c e ty l- l- th io -p -D -

g lucopy ranoside (20 ) . —P re p a ra tio n o f 20 was analogous t o th a t fo r

p re p a ra t io n o f 21 d esc rib ed in th e fo rego ing experim ent. Benzene-

t h i o l (3 sal, 29 mmoles) in 3 N e th a n o lic po tassium hydroxide (8 ml)

was added to te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l bromide (10 .0 g,

24 m m oles), t h a t had been d isso lv e d in warm a b so lu te e thano l (25 m l).

The m ix tu re was shaken fo r 5 h r a t room tem pera tu re and was concen

t r a t e d t o g iv e a crude w hite s o l id . The s o l id was d isso lv e d in

a c e t i c anhydride (20 m l), sodium a c e ta te ( l g) was added, and the

m ix tu re was re f lu x e d fo r 2 h r and th en poured onto ic e and w ater

(500 g ) . The aqueous la y e r was decanted and th e rem aining res id u e

was d is so lv e d in dichlorom ethane (200 ml) and washed w ith s a tu ra te d

sodium hydrogen carbonate (100 m l), w ater (100 m l), and d r ie d

(magnesium s u l f a t e ) . The dichlorom ethane s o lu t io n was concen tra ted

to a sy ru p . The syrup c ry s ta l l iz a e d to g ive 20 in two c ry s ta l crops

as w hite n e e d le s , y ie ld 7 .4 g , 17 mmoles (71%), m .p. 116-117°,

M d 3 “1 5 .8 ° (c 2 . 2 , chloroform ) [ l i t . ^ ° m .p. 117°, [o ]^ ° -4 0 .1 °

( to lu e n e ) and l i t . 31 [ tt]20 - 1 7 .5 0 (c 2 . 5 , c h lo ro fo rm )]."

A nal. C alcd. for~CgQHÔgS: C, 54.53,* H, 5 .49 ; S , 7 .2 8 .

Found: C, 54 .35; H, 5 .44 ; S, 7 .1 6 .

1 HP re p a ra tio n of 2 ,3 ,A ,6 - te tra -Q -a c e ty l- l-S -b e n z o y l~ l- th io -

p-D -glucopyranose (2 9 ) .—Compound 29 was p rep a red by C, V. Holland

accord ing to th e procedure d esc rib ed by H olland , H orton, M il le r ,20

and B h a c c a . ^ 9 compound had m .p. 130-131°, [a ]j) -1 2 ,5 °

(c 1 , chloroform ) [ l i t . 50 m .p. 126°, [c ]^ ° - 1 2 . 44°” ( l , l , 2 , 2 -

te t r a c h lo ro e th a n e ) ] ,

N .m .r. s p e c t r a l s tu d y o f the re a c tio n o f 1 - th io -p -D-g luco -

pyranose p e n ta a c e ta te (16 ) in carbon te t r a c h lo r id e w ith brom ine. —

A suspension o f th e th io a c e ta te (16 , 126 mg) in carbon te t r a c h lo r id e

(1 ml) was p rep a red in an n .m .r . sample tu b e , and a sm all drop of

te tra m e th y ls i la n e was added. The spectrum a t 60 MHz Bhowed a 3 -

p ro to n s in g le t a t T7.59 (SAc), peaks (12 p ro to n s) a t T 7.92, 7 . 9 8 ,

and 8 .00 (OAc) and no s ig n a ls below TA.5. From a s to ck s o lu tio n

o f bromine (15 .60 g , 5 .0 ml) in carbon te t r a c h lo r id e (20 ml) a

250-p l a liq u o t (correspond ing to 6 .3 mmoles o f bromine p e r mole of

16 was added by means o f a sy rin g e to th e suspension o f 16 a t ' “AO0.

The suspended m a te r ia l d isso lv e d ra p id ly . A scan of th e n .m .r .

spectrum was i n i t i a t e d 60 sec a f t e r a d d itio n o f the brom ine, and

was completed 100 sec l a t e r . The spectrum showed no s ig n a ls below

?A .5 , bu t th e SAc s ig n a l had d isap p eared com plete ly and a 3 -p ro to n

s in g le t a t T7.19 had appeared (a c e ty l bromide in carbon te t r a c h lo r id e

shows i t s p ro to n s ig n a l a t T7. 19) . A 12-p ro to n m u lt ip le t was ob

se rv ed a t T " 7.9 (OAc), The spectrum was rescanned 200 sec a f t e r

th e a d d it io n of th e brom ine: t h i s scan , com pleted 100 sec l a t e r ,

resem bled th e p rev io u s one, excep t th a t a lo w - in te n s i ty doub let a t

7 3 .3 , having 2 4 -0 (H" l g ly co sy l bromide l ) ,^ 2 was* 0* *

115

p re s e n t. The l a t t e r s ig n a l in c re a se d in in te n s i ty w ith tim e , and,

a f t e r 1 h r , i t had an in te g ra te d in te n s i ty of one p ro to n ( r e la t iv e

to th e 12-pro ton s ig n a l a t 7 " 7 .9 ) . At t h i s tim e , th e spectrum

was id e n t ic a l w ith th a t o f the g ly co sy l bromide 1 in carbon t e t r a

c h lo r id e , except fo r th e a d d it io n a l 3 -p ro ton s in g le t a t 17.19 (AcBr).#

The re a c tio n so lu tio n was evaporated to dryness and th e re s id u e was

d isso lv e d in carbon t e t r a c h lo r id e . The n .m .r . spectrum of th e so lu

t io n was unchanged, except th a t th e s ig n a l a t 17.19 had d isappeared .

N .m .r. s p e c tra l study o f th e re a c tio n of l - t h i o - a -D-g luco -

pyranose p e n ta a c e ta te (18) in carbon te t r a c h lo r id e w ith brom ine. —

The th io a c e ta te (18, 114- mg) was suspended in carbon te t r a c h lo r id e

(2 ml) in an n .m .r . sample tube and a sm all drop of te tra m e th y l-

s i la n e was added. Although th e th io a c e ta te (18) was q u ite in so lu b le

in carbon te t r a c h lo r id e , th e spectrum a t 60 KHz showed a broadened

3 -p ro ton s in g le t a t 7 " 7 .6 0 (SAc) and a 9 -p ro to n m u lt ip le t a t

7 "8 .0 5 (OAc). A s ig n a l fo r H -l o f 18 was not observed because ofMWth e low s o lu b i l i t y of 18 in carbon te t r a c h lo r id e and no o th er s ig n a l

was observed below 7 ^ ,0 . From th e stock s o lu tio n of bromine des

c rib e d in th e fo rego ing experim ent, a 250-p l a liq u o t (corresponding

to 7 moles o f bromine p e r mole o f 18) was added to th e suspension

of 18 and th e n .m .r . tu b e was shaken v ig o ro u s ly to a id d is s o lu tio n .

A scan of th e n .m .r . spectrum a t a probe tem pera tu re o f 34° was

i n i t i a t e d 35 sec a f t e r th e a d d it io n o f bromine and completed 50 sec

#An n .m .r . spectrum o f a c e ty l bromide in carbon t e t r a

c h lo r id e w ith IMS as a s tan d a rd showed i t s s ig n a l a t 7 7 ,1 9 . The exac t f i e l d p o s i t io n was determ ined by th e normal sidebanding techn ique w ith IKS as th e in te r n a l s ta n d a rd .

116

l a t e r . The spectrum showed no s ig n a ls below bu t a doublet

was p re se n t a t 74 .12 having 2 4 .0 Hz. Most of th e SAc s ig n a l

a t T "7 .6 0 had d isappeared and a s in g le t was p re s e n t a t 77.19

(AcBr). A second scan was i n i t i a t e d 1 min 35 sec a f t e r th e a d d i

t io n of bromine and completed 50 sec l a t e r . The spectrum -was th e

same as th a t d e sc rib e d f o r th e f i r s t scan w ith the excep tion th a t

th e s ig n a l corresponding to SAc a t 7 "7 .6 0 was a b sen t. No s ig n a ls

were observed below 7 4 .0 . A th i r d scan w b s i n i t i a t e d 2 min 35 sec

a f t e r th e a d d itio n o f bromine and completed 50 sec l a t e r . A low

in te n s i ty doub let a t 73 .28 having J-^ 2 4*0 Hz (H-l o f th e g ly co sy l

bromide 1) was p re se n t in a d d itio n to th e s ig n a l a t 7 4 .1 2 , The

l a t t e r s ig n a l was th e more in te n se s ig n a l . A fo u rth scan was

i n i t i a t e d 3 min 50 sec a f t e r th e a d d itio n of bromine and com pleted

100 sec l a t e r . The doub le t a t 74.12 was more in te n se than th e

doublet a t T3.28 and th e rem aining p o r tio n o f the spectrum was ana lo

gous to th a t o f th e t h i r d sc an . At 5 min 50 sec a f t e r bromine ad d i

t io n and a t a scan tim e o f 250 sec th e low f i e l d d o u b le ts , 73 .28 and

T 4 .12 , were o f approx im ate ly equal i n te n s i ty . At 10 min 20 sec a f te r

bromine a d d it io n and a t a scan time o f 250 s e c , the low f i e l d doublet

T3 .28 was much more in te n se than th e doublet a t 74.12* At 14 min

50 sec a f t e r bromine a d d it io n and a t a scan tim e of 250 se c , no s ig

n a l was observed a t 74.12 and the doub let a t 73 .28 p re v a ile d . At

42 min a f t e r th e a d d it io n o f brom ine, the spectrum was id e n t ic a l

w ith th a t o f in carbon te t r a c h lo r id e , except fo r th e a d d it io n a l

3 -p ro to n s in g le t a t 77 .19 (AcBr). The doublet a t 73 .28 had an in

te g ra te d in te n s i t y o f one p ro to n ( r e la t iv e to th e 12 -pro ton s ig n a l

117

a t T *“7 .9 ) . The carbon te t r a c h lo r id e s o lu t io n was evaporated to

a syrup and th e syrup was re d is so lv e d in ch loroforra-d . The 3“

p ro to n s in g le t a t T7.19 was absen t and th e n .m .r . spectrum was

id e n t ic a l to th a t rep o rte d p r e v io u s ly .^ T . l . c , o f th e so lu tio n

rev e a le d a v e ry major component a t Rp 0.87 and f iv e very minor

components, Rf 0 .6 9 , 0 .4 9 , 0 .4 1 , 0 .3 3 , and 0 .2 2 . The so lv e n t was

evapo ra ted to g ive a syrupy re s id u e th a t was su b je c te d to column

chromatography on s i l i c a g e l (5 g) w ith so lv en t A as e lu e n t. The

s e p a ra tio n was m onitored by t . l . c . and ~2 ml f r a c t io n s were c o l

l e c te d . Component, R , 0 .8 7 , was c o lle c te d and evaporated to a sy ru p .

The syrup c ry s ta l l i z e d from e th e r —petro le iu m e th e r to g ive t e t r a - 0 -

ace ty l-a -D -g lu co p y ran o sy l bromide ( l ) , y ie ld 42 mg, 0 .1 mmoles (36%),

m .p. 84-85°, l i t . m . p . 88 -89°. The i . r . spectrum was superposable

w ith th a t of an a u th e n tic sample of

N .m .r. s p e c t r a l s tu d y o f th e re a c tio n o f 1 - th io -p -D -g a lac to -

pyranose p e n ta a c e ta te (17) in carbon te t r a c h lo r id e w ith brom ine.—

A suspension o f th e th io a c e ta te (17, 119 mg) in carbon te t r a c h lo r id e

Cl ml) was p repared in an n .m .r . sample tu b e , and a drop of t e t r a -

m e th y ls ilan e was added. The spectrum a t 60 MHz showed a 3~pnoton

s in g le t a t T7.64 (SAc), peaks (12 p ro to n s) a t T 7.87, 7 .9 3 , 8 . 02 ,

and 8 .07 (OAc), and no s ig n a ls below T4 . 5 . From th e stock s o lu tio n

o f bromine in carbon te t r a c h lo r id e , d e sc rib ed f o r th e brom ination

o f 1 6 , a 250-p.l a liq u o t (corresponding to 7 moles o f bromine p e r

mole o f 17) was added to th e suspension o f 17 a t 34°. The suspended

m a te r ia l d isso lv e d , A scan o f th e n .m .r . spectrum was i n i t i a t e d 30

se c a f t e r a d d itio n of brom ine, and was completed 50 sec l a t e r . The

spectrum showed a d o u b le t a t T3 .3 3 , having g 3 *^ (H -l o f

th e g ly co sy l bromide 2) . 92 The SAc s ig n a l had d isappeared com

p le t e ly and a 3 -p ro to n s in g le t a t T7.19 had appeared (AcBr). A

1 2 -p ro ton m u lt ip le t was observed a t T ~ 7 .9 (OAc). Scanning o f th e

n .m .r . spectrum was con tinued w ith no s ig n i f ic a n t change in th e

spectrum . A fte r 7 min th e low f i e l d d o u b le t, T 3 .33 , had an in

te g ra te d in te n s i t y o f one pro ton ( r e la t iv e to th e 12 -p ro to n s ig n a l

a t 7 ~ 7 .9 ) . A f te r about 2 h r th e s o lu t io n in th e n .m .r . tube was

evaporated t o a sy ru p . T . l . c . rev ea led th e p resence of a p r in c ip a l

component, Rf 0.62 and th re e very minor components, 0 .4 4 , 0 . 32 ,

and 0 .2 1 . The syrup was d isso lv e d in chloroform -d and the n .m .r .

spectrum showed th e absence of th e 3~proton s in g le t a t 77 .19 (AcBr).

The n .m .r . spectrum was id e n t ic a l w ith th a t re p o rte d p re v io u s ly fo rno

te tra -O -a c e ty l-a -D -g a la c to p y ra n o sy l bromide (2 ) . The c h lo ro

form -d s o lu t io n was re -e v ap o ra ted to a syrup and the syrup was

su b je c te d to column chromatography on s il ic a * g e l (5 g) w ith so lv e n t A

as e lu e n t. The s e p a ra tio n was m onitored by t . l . c . and th e major com

ponent (Rf 0 .82 ) was c o l le c te d , evaporated to a sy ru p , and c r y s ta l

l i z e d from ether*—petro leum e th e r to g ive te tra -O -a c e ty l-a -D -

g a la c to p y ran o sy l bromide (2 ) , y ie ld 53.7 mg, 0 .13 mmoles (45^), m .p.

8 1 -82°, [c ] j’8 +206° (c 1 .76 chloroform ) l i t . 93 m.p. 83-84°,

+2i5° (c 1 , ch lo ro fo rm ).

N .m .r. s p e c t r a l s tu d y o f the re a c t io n of 1 - t h io - a - L -arab in o -

pyranose t e t r a a c e t a t e (14) in carbon te t r a c h lo r id e w ith brom ine. —

A s o lu t io n o f th e th io a c e ta te ( ^ , 155 mg) in carbon te t r a c h lo r id e

( l ml) was p rep a red in an n .m .r . tu b e , and a sm all drop of

te tra m e th y ls i la n e was added. The spectrum a t 60 MHz showed a 3"

p ro to n s in g l e t a t T7.66 (SAc) peaks (12 p ro to n s) a t T7.93 an^ 8*00

(OAc) and no peaks below From a s to ck s o lu t io n of bromine,

d e sc rib e d p re v io u s ly f o r th e brom ination of 16, a 250-pl a liq u o t

(co rrespond ing to 4 .2 moles of bromine p e r mole o f 14) was added

to th e s o lu t io n . A scan o f the n .m .r . spectrum a t a probe tem pera

tu r e of 34° was i n i t i a t e d 25 sec a f t e r a d d itio n o f brom ine, and was

com pleted 50 sec l a t e r . The spectrum showed a doub let a t 73 .37 ,

having ^ 3 ,7 Hz (H -l o f th e g ly co sy l bromide %)* The SAc s ig n a l

had d isap p ea red com plete ly and a 3 -p ro to n s in g le t a t 7 7 .1 9 had

appeared (A cBr), A 9 -p ro to n m u lt ip le t was observed a t T ~ 7 .9 (OAc).

F u rth e r scann ing o f th e n .m .r . spectrum over a 5 min p e rio d rev ea led

no s ig n i f ic a n t change in the spectrum . A fte r 5 .5 min th e low f i e l d

d o u b le t, T3 .3 7 and an in te g ra te d in te n s i ty of one p ro to n ( r e la t iv e

t o th e 9 -p ro to n s ig n a l a t 7 ~ 7 .9 ) , A fte r about 3 b r th e so lu tio n

i n th e n .m .r . tube was evaporated to a yellow sy ru p . T . l . c . o f th e

sy rup re v e a le d th e p resence of fo u r components. There was one major

component, R . 0 .92 and th re e minor components, 0 .4 4 , 0 .3 7 , and

0 .2 1 . The syrup was d isso lv e d in chloroform -d and an n .m .r . spec

trum was made o f th e s o lu t io n . The spectrum was id e n t ic a l w ith

t h a t re p o r te d by Horton and T u rn e r^ f o r tr i-O -a co ty l-J i-D -a ra b in o -

py ranosy l brom ide. The chloroform -d s o lu t io n was evaporated to a

syrup and th e syrup was c r y s ta l l i z e d from e th e r —petro leum e th e r to

g iv e 2 , y ie ld 45 mg, 0 .13 mmoles (2850, m.p. 133-139°, [c ]^ 8 +279°

(c 1 .24 chloroform ) [ l i t . 9^ m.p. 139°, [ a ] Q +283.6° (ch lo ro fo rm )].

120

N .m .r. s p e c t r a l s tu d y o f th e re a c tio n of l - th io - f t - D-x y lo -

pyranose t e t r a a c e t a t e (15) in carbon te t r a c h lo r id e w ith brom ine.—■........I —* ' I .1.11. .. fttfV ■ I ■ ■■■■ — —W — I — ■ I.— ■ 1 . .!■■■■ ■The th io a c e ta te (lj>, 109 mg) was m ostly d isso lv e d in carbon t e t r a

c h lo rid e ( l ml) in an n .m .r , sample tube and a drop o f te tra m e th y l-

s i la n e was added. The spectrum a t 60 MHz showed a 3 -p ro to n s in g le t

a t '*'7.63 (SAc) and a 9 -p ro to n broadened s in g le t a t T8.00 (OAc) and

no s ig n a ls below T 4 .5 . From th e s to c k s o lu tio n o f bromine in carbon

te t r a c h lo r id e d e sc rib e d f o r th e b rom ination of 16 was added a 250-ul

a liq u o t (co rrespond ing to 5 .9 moles o f bromine p e r mole o f 15) to

th e s o lu tio n of 15. A scan o f the n .m .r . spectrum a t a probe tem-

p e ra tu re o f 34° was i n i t i a t e d 30 sec a f t e r a d d it io n of bromine and

was completed 50 sec l a t e r . The spectrum showed a d o u b le t a t T 3.44,

having 4*0 Hz (H -l o f th e g ly co sy l bromide A). The SAc s ig n a l

had d isappeared com plete ly and a 3 -p ro to n s in g le t a t T7.19 had

appeared (AcBr). A 9 -p ro ton m u lt ip le t was observed a t T -7 .9 5 (OAc).

Scanning o f th e n .m .r . spectrum was con tinued fo r 7 min w ith no s ig

n i f ic a n t change in the spectrum . A f te r 7 min th e low f i e l d d o u b le t,

T 3.44 , had an in te g ra te d in te n s i t y o f one p ro to n ( r e l a t iv e to th e

9 -p ro to n s ig n a l a t T - 7 .9 5 ) . A fte r about 2 h r th e s o lu t io n in the

n .m .r . tube was evapora ted to a sy ru p . T . l . c . o f th e syrup rev ea led

th e p resence o f fo u r components, Rf 0 .92 (very m ajor) and 0 .5 2 , 0 .4 4 ,

and 0 .21 (m inor). The syrupy re s id u e was d isso lv e d in chloroform -d

and th e n .m .r . spectrum was id e n t i c a l w ith th a t re p o r te d previously^**

fo r tr i-O -a c e ty l-a -D -x y lo p y ra n o sy l bromide (4 ) . The chloroform -d

s o lu tio n was evapora ted to a c r y s ta l l in e re s id u e . The re s id u e was

r e c r y s ta l l i z e d from e th e r—petro leum e th e r to g ive th e bromide 4

121

as f in e n e e d le s , y ie ld 75 .1 mg, 0 ,22 mmoles (6 7 $ ), m .p, 99-100°,

[a]28 +215° (c 1 .4 , chloroform ) [ l i t . 96 m.p. 102°, [a ]g ° +212.2° (c

2 .5 , ch lo ro form ).

N .m .r. s p e c t r a l s tu d y o f th e re a c tio n of 1 -th io -fJ-D -rib o -

pyranose t e t r a a c e ta t e (28) in carbon te t r a c h lo r id e w ith brom ine.—^ ■ I ■ I ■ ■ I ........................................ I I I I ■ I ■ I I ■ . ! ■ 1 ■ * 1 " 1

The th io a c e ta te (28 , 110 mg) was d isso lv e d in carbon te t r a c h lo r id e4WM

( l ml) in an n .m .r . tube and a drop o f te tra m e th y ls i la n e was added

to th e s o lu t io n . The spectrum a t 60 MHz showed a 3 -p ro to n s in g le t

a t 7 7 .6 7 (SAc), and peaks (9 p ro to n s) a t 77 .92 and 8 .02 (OAc) and

no s ig n a ls below 7 4 .4 . From th e s to c k s o lu t io n of bromine d escrib ed

fo r th e brom ination o f 16 , was added a 250-pl a l iq u o t (c o rre s

ponding to 5 .9 moles o f bromine p e r mole of 28) to th e so lu tio n

o f 28. A scan o f th e n .m .r . spectrum a t a probe tem perature o f 34°

was i n i t i a t e d 13 sec a f t e r th e a d d it io n of bromine and was completed

50 sec l a t e r . A broadened s in g le t was observed a t 7 3 .7 0 (H-l o f

th e g ly co sy l bromide ^ 6 ) . The SAc s ig n a l had d isappeared com pletely

and a 3 -p ro to n s ig n a l a t T 7.19 had appeared (AcBr), A 9 -p ro ton

m u lt ip le t was observed a t 7 - 8 .0 (OAc). Scanning o f th e n .m .r .

spectrum was con tinued f o r 7 min w ith no s ig n i f ic a n t change in th e

spectrum . A fte r 7 min th e low f i e l d , broadened s i n g l e t , 7 3 .7 0 ,

had an in te g ra te d i n t e n s i t y o f one p ro to n ( r e l a t iv e to th e 9 -p ro ton

s ig n a l a t 7 —8 .0 ) . A f te r about 4 h r th e carbon te t r a c h lo r id e s o lu

t io n was evaporated to a syrupy re s id u e . T . l . c . of th e res id u e

rev ea led a major component, R^, 0 .84 and th re e minor components,

“ £ 0*34, and 0 . 2 3 , The re s id u e was d isso lv e d in chloroform -^

and th e n .m .r . spectrum was id e n t ic a l w ith th a t p re v io u s ly

122

r e p o r t e d ^ fo r tr i-O -a c e ty l-p -D -r ib o p y ra n o sy l bromide (^6 ) . The

w idth a t h a lf -h e ig h t o f th e H -l s ig n a l was 3*0 Hz. A fte r about

4 h r th e chloroform -d s o lu t io n was evaporated to a syrup and th e

syrup was c r y s ta l l i z e d from e th e r to g ive 36 as c o lo r le s s , s to u tJVMc r y s ta l s , y ie ld 39 mg, 0 .11 mmoles (33%), m.p. 9 5 ° , [a ]p -208°

(c 1 . 3 , chloroform ) [ l i t .^ ^ 1 m.p. 96° , Ca 3^ -209 .3 ° (ch lo ro fo rm )].

(136) P. A. Levene and R. S. T ipson, J . B io l. Chem., 22,

109 (1931).

N .m .r. s p e c t r a l study o f th e re a c tio n o f benzyl 2 ,3 ,4 ,6 -

t e t r a - Q-a c e ty l - l - t b i o - p - D-glucopyranoside (21) in carbon t e t r a -

c h lo rid e w ith b rom ine.—The l- th io -D -g lu c o s id e (21, 122 mg) was■ ' t t — — —-p a r t ly d is so lv e d in carbon te t r a c h lo r id e ( l ml) in an n .m .r . sample

tube and a drop o f te tra ra e th y ls i la n e was added. The 60 MHz spec

trum showed a 5 -p ro ton s in g l e t , 72 .80 (P h ), '*4 . 83- 5 .28 and 5 .60-

5 .99 (m u lt ip le ts , th r e e and th re e p ro to n s , H -l, 2 , 3 , 4 , 6 , 6 ' ) ,

T6.14 (2 -p ro to n d o u b le t, b en zy lic CH^), 7 6 ,2 8 -6 .6 9 (m u lt ip le t , H-5) ,

77 •94, 8 .0 5 , and 8 .0 8 ( th r e e , s i x , and th re e p ro to n s in g le t s , OAc).

From th e s to c k s o lu t io n o f bromine in carbon te t r a c h lo r id e d escrib ed

f o r th e brom ination o f 16 was added a 250-p l a l iq u o t (corresponding

to 7 .2 moles o f bromine p e r mole o f 2 1 ). A scan o f th e n .m .r .JVMspectrum a t a probe tem pera tu re of 34° was i n i t i a t e d 17 sec a f t e r

a d d it io n o f bromine and was com pleted 50 sec l a t e r . The spectrum

showed th e absence o f a doub let a t 76 .14 (b en zy lic CH,,) and the

appearance o f a broadened s in g le t a t T5.77 and no lo w -f ie ld doublet

123

was p re se n t t o in d ic a te the p resence o f g ly co sy l bromide J,. The

spectrum was scanned fo r 7 min 30 sec a f t e r th e a d d itio n of bromine

and no a p p re c ia b le change in th e spectrum occurred . The spectrum

was scanned a t 8 min 35 sec a f t e r th e a d d itio n of bromine a t a scan

speed o f 250 sec and a lo w -f ie ld doub let appeared as a weak s ig n a l

T 3 .4 0 , having 2 4 .0 Hz of "t*10 g lycosy l bromide 1 ) . The

spectrum was scanned 25 min a f te r th e ad d itio n o f bromine and th e

lo w -f ie ld d o u b le t, T3 . 4 0 , had an in te g ra te d in te n s i ty o f 0 .32 p ro tons

( r e l a t iv e t o OAc p ro to n s ) . The lo w -f ie ld doub let had an in te g ra te d

in te n s i ty o f 1 p ro to n ( r e la t iv e to OAc p ro to n s) 1 h r 30 min a f t e r

th e a d d it io n o f brom ine. At t h i s tim e , the spectrum was id e n t ic a l

w ith th a t o f th e g ly co sy l bromide 1 in carbon te t r a c h lo r id e , except

fo r th e a d d it io n a l 5-proton s in g le t a t T2.71 and a 2-proton s in g le t

a t T5 . 57# The carbon te t r a c h lo r id e s o lu tio n was evaporated to a

syrupy re s id u e . T . l . c . o f th e re s id u e rev ea led a m ajor component,

■'fi 0 .8 3 and th re e minor components, R^ 0 .51 , 0 .4 3 , and 0 .3 2 . The

nbsidue was d is so lv e d in chloroform -d and th e n .m .r . spectrum was92e s s e n t ia l ly th e same as rep o rte d p re v io u s ly fo r jj, w ith th e ex

c e p tio n o f th e p resence o f a 5 -p ro ton s in g le t a t T2.72 and a 2 -p ro to n

s in g le t T 5 .5 3 . The chloroform -d s o lu t io n was evaporated to a syrup

and th e syrup was chrom atographed 01 s i l i c a g e l (5 g) w ith so lv e n t A/

as e lu e n t. The s e p a ra tio n was m onitored by t . l . c . and th e compound

Rf 0 .83 was i s o la te d and evaporated to a c o lo i le s s sy rup . The

syrup c r y s ta l l i z e d from e th e r—petroleum e th e r to give t e t r a - 0 -

a c e ty l-a -p -g lu c o p y ra n o sy l bromide ( l ) , y ie ld 31 mg, 0 .07 mmoles (26%),

12 U

m .p. 86 -87°, [a ]^ 8 +188° (c 1 .0 , chloroform ) [ l i t . 91 m .p. 88-89°,

[a ] j. +198° (c 2 , c h lo ro fo rm )]. The c r y s ta l l in e compound was d i s

so lv ed in ch loroform -d . I t s n .m .r . spectrum was id e n t ic a l w ith

t h a t p re v io u s ly r e p o r t e d .^ The i . r . spectrum was superposab le

on th a t o f an a u th e n tic sample of 1 .

N .m .r. s p e c t r a l s tu d y o f the re a c t io n o f phenyl 2 ,3 ,A ,6 -

t e t r a - O-a c e ty l-1 -1 h io -p -D-glucopyranos ide (20) in carbon t e t r a -

c h lo r id e w ith b rom ine .—The 1 -th io -D -g lu co sid e (20, 103 mg) was ■ ■ 1 11 1 1 1 ■■■■ ~ *alm ost in so lu b le in carbon te t r a c h lo r id e (2 ml) in an n .m .r ,

sample tu b e . A drop of te tra m e th y ls i la n e was added to th e carbon

t e t r a c h lo r id e . The 60 MHz spectrum showed a weak a c e ty l s ig n a l as

a broadened doub let T *“8 ,0 and a weak a ry l s ig n a l as a very broad

s i n g l e t , T ~ 2 .7 . From th e stock s o lu t io n of bromine in carbon

te t r a c h lo r id e d escrib ed f o r the brom ination o f 3,j5 was added a

2 5 0 -p l a l iq u o t (co rrespond ing to 8 ,5 moles of bromine p e r mole of

2 0 ) . The n .m .r . tube and i t s co n ten ts were shaken v ig o ro u s ly to

a id d is s o lu t io n . A scan o f th e n .m .r . spectrum a t a probe tem pera

tu r e o f 34-° was i n i t i a t e d A0 sec a f t e r a d d it io n o f bromine and was»

com pleted 50 sec l a t e r . The spectrum showed a lo w -f ie ld d o u b le t,

T3.A2 (H -l of the g ly co sy l bromide 1 ) , having J-^ 2 4*0 Hz and a

low f i e l d m u lt ip le t **2.13-2.69 (a ry l p ro to n s ) . Scanning o f the

spectrum was con tinued w ith no observable change. At 7 min a f t e r

th e a d d it io n o f bromine th e in te g ra te d in te n s i ty o f th e low f i e l d

d o u b le t, T3 .A2 , was 1 p ro to n ( r e la t iv e to th e OAc). The carbon

te t r a c h lo r id e s o lu t io n was evaporated to a sy ru p . T . l . c . of th e

syrup rev ea led a m ajor component R . 0 .80 and fo u r minor components,

125

Rf 0.4.9, 0 .4 3 , 0 .33 , and 0 .2 5 . The syrup was d isso lv e d in c h lo ro

form -d. The n .m .r . spectrum o f the p roduct was the same as th a t92rep o rte d by Horton and Turner w ith th e excep tion o f a lo w -f ie ld

m u lt ip le t cen te red a t 7 2 .6 8 , The chloroform -d s o lu t io n was evaporated

to a syrup and th e syrup was chromatographed on s i l i c a g e l (5 g) w ith

so lv e n t A as e lu e n t. Component R , 0 .80 was se p a ra te d and c r y s ta l l i z e d

from e th e r—petroleum e th e r to y ie ld te tra -O -ace ty l-a -D -g lu co p y ran o -

s y l bromide ( l ) , 23 mg, 0 .06 mmoles (26%), m.p. 87-88°, [ a ] ^ +199°

(c 0 .7 6 , chloroform ) [ l i t . ^ * m .p. 88-89°, +198° (c 2 , ch lo ro fo rm )].

A chloroform -d so lu tio n o f the product gave the same n .m .r , spectrum

as th a t rep o rte d p re v io u s ly f o r te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l

bironiide (].)

N .m .r. s p e c tr a l s tu d y o f th e a c tio n o f bromine on 2 ,3 ,4 ,6 -

t e t r a -O- a c e ty l - l - S -b e n z o y l- l- th io -p -D-glucopyranose (29) in carbon

t e t r a c h lo r id e .—A suspension of 29 (123 mg) in carbon te t r a c h lo r id e

(1 ml) was p repared in an n .m .r . tu b e , and a drop o f te tra m e th y l-

s i la n e was added. The spectrum a t 60 MHz showed a low f i e l d m u lti

p l e t , T 2 .0 -2 .7 (a ry l p ro tons) and s in g l e t s , T 7 .99 , 8 .0 2 , and 8.05

( th re e , th re e , and s ix p ro to n s , OAc). The rem aining p o r tio n of th e

spectrum was no t observable because o f th e low s o lu b i l i t y o f 29 in

carbon te t r a c h lo r id e . From th e s to ck s o lu tio n of bromine in carbon

te t r a c h lo r id e d escrib ed fo r th e brom ination o f 16 was added a

250-p l a liq u o t (corresponding to 7 .5 moles o f bromine p e r mole of

2 9 ) . A scan o f the n .m .r . spectrum a t a probe tem perature o f 34°

was i n i t i a t e d 17 sec a f t e r bromine a d d itio n and was completed 50 sec

l a t e r . The n .m .r , spectrum showed a weak s ig n a l fo r a low f i e l d

126

doub let a t 7 3 .4 0 , having 2 4 .0 Hz (H -l o f th e g ly co sy l bromide l ) .

A second scan o f th e n .m .r . spectrum uas i n i t i a t e d 1 min 80 sec

a f t e r th e a d d itio n o f bromine and completed 50 sec l a t e r . The lo u -

f i e l d doublet uas c le a r ly d is c e rn ib le . Scanning o f th e n .m .r .

spectrum uas continued fo r 7 min u i th no ap p rec iab le change in th e

spectrum . At th i s tim e th e in te g ra te d in te n s i ty of th e low f i e l d

doub let uas one p ro to n ( r e l a t iv e to th e a c e ty l s ig n a ls a t 7 '“7 .9 )

and th e spectrum was id e n t ic a l u i th th a t of th e g ly co sy l bromide jL

in carbon te t r a c h lo r id e , excep t fo r a m u lt ip le t T i .8 4 -2 .6 0 . The

s o lu t io n was evaporated to a syrupy re s id u e . T . l . c . o f th e syrup

rev ea led a m ajor component, R^ 0.82 and th re e minor components,

Rf 0 .5 1 , 0 .4 3 , and 0 ,2 2 . The syrup uas d isso lv e d in chloroform -d

and the n .m .r . spectrum uas id e n t ic a l w ith th a t p re v io u s ly rep o rte d92by Horton and Turner u i th th e excep tion o f th e p resence of a low

f i e l d m u lt ip le t , 7 1 .9 4 -2 ,8 0 . The s o lu tio n was evaporated to a

syrup and th e syrup uas chrom atographed on s i l i c a ge l (5 g) u i th

so lv e n t A as e lu e n t. The component, 0.82 uas i s o la te d and

c ry s ta l l iz e d from e th e r—petro leum e th e r to y ie ld 1 , 27 mg, 0 ,07

mmoles (27^), m.p, 85-86° [ l i t . ^ m .p. 8 8 -8 9 °]. A s o lu t io n o f th e

product in chloroform -d gave th e same n .m .r , d a ta as rep o rte d

p r e v io u s ly ^ and th e i . r , spectrum was superposab le u i th th a t o f

an a u th e n tic sample o f te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l bromide ( l ) •

T e tra -Q -ace ty l-p -D -g lu co p y ran o sy lsu lfen v l bromide (22)~~ _ 11 __r“ - - - - - mm

A. From 16 in carbon t e t r a c h lo r id e .—The s u lfe n v l bromide 227^W ' ■ ■ i ■uas p repared accord ing to th e method d e sc rib e d .b y the au th o r in h is

M aster of Science t h e s i s . ^ To a suspension o f

127

1 -th io -p -D -g lucopy ranose p e n ta a c e ta te ( l6 , 20 .00 g , 4 9 .2 mmoles) ino

anhydrous carbon te t r a c h lo r id e (200 ml) cooled to about -10 uas

added a s o lu t io n o f bromine (9 .0 ml, 176 mmoles) in carbon t e t r a

c h lo r id e (40 ml) and th e m ix ture uas s t i r r e d fo r 2 -3 min a t about

-1 0 ° . V o la ti le m a te r ia ls were then ra p id ly removed on a ro ta ry

ev ap o ra to r a t '■*30O/ ;:10 t o r r . , t o g ive 22 as a p a le - y e l l ou ,• c r y s t a l

l i n e r e s id u e , y ie ld 22 .27 g (102^, m .p. 102-104°, Ca ] ^ -6 6 .7 ° (c 2 .1 ,

te tra h y d ro fu ra n ) changing to -114° a f t e r 14 h r ;X 5.72 (OAc),max

11.20 pm (a x ia l H a t C - l ) , SAc absen t n .m .r . d a ta (100 MHz,

ch lo ro fo rm -d ): T4 . 55-5 .02 (3 -p ro to n m u l t ip le t ) , 5.35 ( l -p ro to n

m u lt ip le t (H -l, 2 , 3» 4)» T5 . 6 3 -5 .99 (2 -p ro ton m u lt ip le t , H-6, 6 1) ,

T6.14 (1 -p ro to n m u lt ip le t , H -5),39 T 7.90 , 7 .9 2 , 7 .9 7 , 8 .0 0 (12 p ro to n s ,

a c e ty l s ) .

A nal. C alcd. fo r C^H-^BrOqS: C, 3 7 .9 3 ; H, 4 .3 2 ; B r, 18.03;

S , 7 .2 3 . Found: C, 3 7 .9 9 ; H, 4 .3 9 ; B r, 17 .52 ; S, 7 .5 1 .

The product gave an X-ray pouder d i f f r a c t io n p a t te rn id e n t ic a l

u i th th a t p re v io u s ly r e p o r te d .9^ Rapid r e c r y s t a l l i z a t i o n of th e

p roduct from carbon te t r a c h lo r id e gave an alm ost q u a n ti ta t iv e r e

covery o f 22 , having p h y s ic a l c o n s ta n ts e s s e n t ia l ly id e n t ic a l u i th

those of th e m a te r ia l f i r s t i s o la t e d . T . l . c . o f 22 shoued a

p r in c ip a l component having Rf 0.45 and minor components having R ,

0 .7 6 , 0 .7 1 , and 0 .2 9 , a lthough none o f th ese components could

a c tu a l ly be a t t r ib u te d to 22 i t s e l f , because o f th e p ro b a b i l i ty

t h a t 22 undergoes decom position on th e ad so rb en t.

Compound 22 p rep a red by the above procedure uas used in a l l

p re p a ra tio n s d e sc rib ed in t h i s d i s s e r t a t io n , u n le s s s t a te d o th e ru is e .

X 28

B. By brom ination o f t e r t - b u ty l t e t r a -Q-a c e ty l - l - t h io - p -D-

g lucopyranoside (19) in carbon te t r a c h lo r id e .- -T o a s o lu t io n of■ — ■ i i ■ ' — 1 "■ ' ■■ --- 1 -th io g ly c o s id e 1^ (516 mg, 1 .2 3 mmoles) i n carbon te t r a c h lo r id e

(20 ml) a t -10° was added bromine (0.75 m l, 15 mmoles); a f t e r 1 .5

min a t -1 0 ° , th e m ixture was ra p id ly evaporated a t 30° t o g ive

th e s u lfe n y l bromide as a ye llow , c r y s ta l l in e s o l id , y ie ld 548 mgo

(101%), m .p. 97-99 . By com parative i . r . and n .m .r . s p e c tra , and

by X-ray powder d i f f r a c t io n d a ta , t h i s p roduct was id e n t ic a l w ith

22 p repared by method A,Mm *”

To a suspension o f th e product (463 mg) i n carbon t e t r a

c h lo rid e (40 ml) was added a s o lu tio n o f b en ze n e th io l (0 ,5 g) in

carbon te t r a c h lo r id e (9 .5 m l) ,7and th e m ixture was kep t 1 h r a t

25°. The r e s u l t in g s o lu tio n was washed su c c e ss iv e ly w ith w ater,

s a tu ra te d aqueous sodium hydrogen ca rb o n a te , and w a te r, d r ie d

(magnesium s u l f a t e ) , and evaporated to d ryness. The re s id u e was

c r y s ta l l i z e d from e th a n o l—petro leum e th e r to g ive phenyl t e t r a - 0 -

ace ty l-p -D -g lu co p y ran o sy l d is u l f id e (2 ^ ) ,7^ ,7S y ie ld 200 mg (34%),

m .p. 123-125°, id e n t ic a l w ith an a u th e n tic sample*^ >78 by mixed

m .p ., com parative i . r . and n .m .r . s p e c t r a , and X -ray powder d i f - 73f r a c t io n d a ta .

Extended brom ination of t e r t - b u ty l t e t r a -O -a c e ty l - l - t h io -

p-D-glucopyranoside (1 9 ) .—To a suspension of the 1 -th io g ly co s id e

19 (534 mg, 1 .27 mmoles) in carbon te t r a c h lo r id e (20 ml) was added

bromine (1 .5 m l, 29 mmoles). The r e s u l t a n t , c le a r s o lu t io n was

k ep t fo r 60 h r a t 25°, and evaporated to d ryness; a s o lu tio n of

th e r e s u l ta n t syrup in d ichlorom ethane was washed w ith aqueous

129

sodium hydrogen carb o n ate , d r ie d (magnesium s u l f a t e ) , d eco lo rized

u i th carbon , and evaporated to a syrup . C ry s ta l l iz a t io n of th e

syrup from e th e r—petroleum e th e r gave te tra -O -a c e ty l-a -D -g lu c o -

pyranosy l bromide ( l ) , y ie ld 167 mg (32^), m.p. 82-85°, id e n t ic a l

w ith an a u th e n tic sample of 1 by t . l . c . and i . r . and n .m .r .

s p e c tra . T . l . c . o f the mother l iq u o r s in d ic a te d th a t 1 was

th e p r in c ip a l component, a minor component had 0 .4 6 .

When th e re a c tio n was fo llow ed by n .m .r . spectroscopy a t

" 4 0 ° , th e 9 -p ro to n s ig n a l a t T8.61 fo r th e t e r t -b u ty l group of 19

was absent 1 min a f t e r th e a d d itio n of brom ine, and th e spectrum

showed no s ig n a l below T 4 .5 . A 9 -p ro ton s ig n a l a t T8.19 was ob

se rv ed , A fte r 14 h r , th e spectrum showed a 1 -p ro to n doublet a t

3 .2 7 , 2 ^z * an( was cl ° SGly s im ila r to th a t of th e g lucosy l

bromide 1 , except fo r th e p resence o f th e 9“pro to n s in g le t a t T g.19.

Form ation o f b i s ( t e t r a -O-a c e ty l- f l-D-g lucopyranosy l) d is u lf id e

(?4) by slow brom ination of th e 1 -th io g ly c o s id e (1 9 ) .—Bromine" ■ - i - i i . _ r _ . _

(0 ,35 ml, ~7 mmoles) was added dropwise during 3 h r to a so lu tio n

o f 19 (544 mg, 1 .29 mmoles) in carbon te t r a c h lo r id e (30 m l), and

th e r e a c t io n was m onitored by t . l . c . At th e end of th e 3 -h r p e rio d ,

on ly a t r a c e o f 1J? rem ained, and th e m ajor component corresponded

t o th e d ig lu c o sy l d is u lf id e 24; a t r a c e of th e p roduct having Rf

0 .39 was a ls o p re s e n t . E vaporation of th e s o lu t io n , and c r y s ta l

l i z a t i o n o f th e re s id u e from e th e r—petroleum e th e r , gave th e

d ig lu co sy l d i s u l f id e 2£, y ie ld 358 mg (765(1), m .p. ( one r e c r y s ta l

l i z a t i o n ) 140-1410 , id e n t ic a l w ith a u th e n tic 2 4 ^ by mixed m .p .,

1 . r . and n .m .r . s p e c tra , and X -ray powder d i f f r a c t io n p a t te rn .

130

F ra c t io n a l r e c r y s ta l l i z a t io n of th e mother l iq u o rs gave

1 3 .A mg (2.5%) o f th e s t a r t i n g m a te r ia l l g .

R eac tio n of th e su lfe n y l bromide 22 w ith t e r t - b u ty l t e t r a -

O -a ce ty l- l- th io -ji-D -g lu c o p y ran o s id e (19) to g ive th e d is u lf id e" ■ " 1 1 * ~ ~ ■— “ ■ — ■ 1 ■ - — ............................. i i i • ii

(24.)'.—A suspension of th e g lu co sy l s u lfe n y l bromide 22 (1.151 g ,AAV2 .6 0 mmoles) in carbon te t r a c h lo r id e (50 ml) was mixed u i th a s o lu

t io n o f 19 (1 .060 g , 2 .52 mmoles) in carbon te t r a c h lo r id e (20 ml)

and th e m ix tu re uas shaken fo r 16 h r a t room tem p era tu re . The

r e s u l t a n t , c le a r s o lu tio n uas washed su c c e ss iv e ly w ith aqueous

sodium hydrogen carbonate and u a te r , d r ie d (magnesium s u l f a te )

and ev ap o ra ted to d ry n ess . C ry s ta l l iz a t io n of th e re s id u e from

e th a n o l—petro leum e th e r gave th e d ig lu c o sy l d is u lf id e 24; y ie ld

( in th r e e c ro p s) 1.314 g (70$), id e n t ic a l w ith an a u th e n tic sample

by t . l . c . , mixed m .p ., i . r . and n .m .r , s p e c tra , and X-ray powder

d i f f r a c t i o n p a t te r n .

T . l . c . o f the mother l iq u o rs showed a m ajor component co r

respond ing t o 24 and a minor component corresponding to 19.

An a liq u o t o f th e re a c tio n m ixture a f t e r 16 h r was examined

by n .m .r . spectroscopy a t 60 MHz. The 9 -p ro to n s in g le t a t T8.61

(SCMe_) p re s e n t in th e spectrum o f th e s t a r t i n g 1 -th io g ly c o s id e 19

had d im in ish ed to low in te n s i ty , and a sh arp s in g le t a t "*8.19,

co rresp o n d in g to t e r t - b u ty l bromide form ed, was observed. The

r e a c t io n m ix tu re was evaporated , and th e re s id u e was d isso lv e d in

carbon t e t r a c h lo r id e . The s ig n a l a t T8.19 (Me^CBr) was no lo n g er

o b se rv ab le in th e n .m .r . spectrum o f th i s s o lu t io n .

131

R eaction of* the su lfe n y l bromide 22 w ith dry e thano l to1 " MM ' - ' - 1 v- _rgive the d is u l f id e 2 4 . —Dry e thano l (50 ml) was added to th e s u l

fe n y l bromide 22 (p repared from 1 .90 g of 16 ) .and th e yellow re a c tio n«k*M ++++

m ixture was k ep t f o r 20-30 min a t room tem pera tu re ; w hite need les

were then p re s e n t , and t . l . c . in d ic a te d th e presence o f a s in g le

component, R . 0 .5 3 , corresponding to th e d is u lf id e 24 , No component

having Rp 0 .39 (corresponding to the oxide ^ 0 ) was d e te c te d . To the

re a c tio n m ixture was added 50 ml o f s a tu ra te d aqueous sodium hydro

gen carbonate s o lu t io n , and the m ixture was co n cen tra ted to remove

e th a n o l. The r e s u l t in g aqueous suspension was e x tra c te d w ith two

50-ml p o r tio n s o f d ichlorom ethane, and th e e x tra c ts were combined,

washed w ith w ater, d r ie d (magnesium s u l f a t e ) , and evaporated . C ry s ta l

l i z a t i o n o f the re s id u e from e th an o l gave th e d ig lu co sy l d is u lf id e

24 , y ie ld 847 mg ( 50/6) , m.p. ( a f t e r r e c r y s ta l l i z a t io n from e th an o l)

141-142°, id e n t ic a l w ith a u th e n tic 24 by t . l . c . and X-ray powderMMd i f f r a c t io n p a t te r n .

T . l . c , o f th e mother l iq u o rs showed a m ajor component having

th e m o b ility of th e d is u l f id e 2 4 , and tr a c e s o f components having

Rf 0.77 and 0 .1 2 . No component corresponding to the oxide 30h.(Rf 0 .39) was p re s e n t .

The experim ent was rep ea ted w ith su lfe n y l bromide 22 (fromMM2 .3 2 g o f 16) in d ry e th an o l (50 m l). A f te r 20 min, the w hite

need les o f 24 th a t had formed were f i l t e r e d oCQ y ie ld 548 mg (26%)

m.p. 142-143°. The f i l t r a t e was c o lle c te d in a f la s k co n ta in in g

a - to lu e n e th io l ( l ml) in dry e th an o l (10 m l). A fte r 10 min a t

132

25° , t . l . c . o f the m ixture showed no component having th e m o b ility

(Rf 0 . 88 ) of benzyl to tra -O -ace ty l-p -D -g lu co p y ran o sy l d is u lf id e

(37 )73 ,78 in d ic a t io n th a t th e s u lfe n y l bromide 22 had been com-

p l e t e ly decomposed by e th an o l w ith in 20 min.

B is ( te tra -O -a c e ty l-p -D -glucopyranosy l d is u lf id e mono-oxide

(30) by o x id a tio n o f d is u l f id e 24 w ith m-chloroperoxybenzoic a c id . —

A s o lu t io n o f the d is u l f id e 24- (264 mg, 360 nmoles) and m -chloro-MMperoxybenzoic a c id (49 mg, 80% pure by t . l . c . , 230 pmoles of o x idan t)

in chloroform (50 ml) was k e p t a t 25°. A fte r 40 min, t . l . c . in d i

c a ted the p resence o f two components, R^ 0 .51 and 0 . 3 9 , in app rox i

m ately equal amountsj no change was no ted a f t e r 4 h r . A dd itiona l

ox idan t ("50 mg, 230 pmoles) was added, and a f t e r 1 h r t . l . c .

in d ic a te d no s ig n i f ic a n t change in th e m ix tu rej i t was th e re fo re

washed su c c e ss iv e ly w ith aqueous sodium hydrogen carbonate s o lu tio n

(50 ml) and w ater (50 m l), d r ie d (magnesium s u l f a t e ) , and evaporated

t o d ryness, and th e re s id u e was t r i t u r a t e d w ith e th an o l (10 m l),

whereupon th e mono-oxide 30 c r y s ta l l i z e d as c o lo r le s s , m icroscopic

n e ed le s , y ie ld 110 mg (41%), m .p. 150-151°. R e c ry s ta l l iz a tio n

from ho t e th an o l gave pure ,30 , m.p. 152 . 5- 153° , - 52 . 1 °

(c 2 .5 , chloroform )} R^ 0.39} 1 5.72 pm (OAc); n .m .r . d a ta

(100 MHz, ch lo ro fo rm -d): ? 4 .36-5 .18 (m u lt ip le ts , H - l , 2 , 3 , 4 ) ,

T5 .76 (m u lt ip le t , H-6 ) , T "6 .1 7 (m u lt ip le t , H -5), T7 . 90 , 7 .9 5 ,

7 .9 6 , and 7 .98 ( s in g le t s , a c e ty l s ) ; X -ray powder d i f f r a c t io n d a ta :

11.86 s (2 , 2 ) , 10.45 s (2 , 2 ) , 7 .68 s (2 , 2 ) , 5 .43 s ( 3 ,3 ) , 5.07 m,

4 .9 5 s (3 ,3 ) , 4 .67 vw, 4 .44 vs ( l ) , 4 .2 9 w.

133

A nal. Calcd. fo r ^28^38^19^2* 5 .16 ; S , 8 .6 3 ;

0 , 4 .9 2 . Found: C, 45 .17 ; H, 5 .18 ; S, 8 . 86 ; 0 , 4 0 .9 4 .

The p roduct 30 had extrem ely low s o lu b i l i t y in cold e th a n o l,MWi n c o n tra s t t o th e d is u lf id e 24, which was m oderately so lu b le ; th eAMtwo compounds were r e a d i ly sep a rab le because o f th i s d if fe re n c e .

R eac tion o f th e s u lfe n y l bromide 22 w ith w ater to g ive■ » . ■ — . I ......................................... « I ■ ■ I I WI I ■ M W ■■ I I . I I I I ■ ■ —

th e d is u l f id e mono-oxide 30 . —A suspension of 22 p repared from

1.043 g o f 16 in carbon te t r a c h lo r id e (40 ml) was shaken w ithMWw ater (3 ml) fo r 40 min a t 25°. The so lv e n ts were evaporated

from th e r e s u l ta n t w hite su spensio n , th e re s id u e was d isso lv e d

in dichlorom ethane (100 m l), and th e s o lu t io n was washed su cces

s iv e ly w ith s a tu r a te d aqueous sodium hydrogen carbonate s o lu t io n

and w a te r, d r ie d (magnesium s u l f a t e ) , and evaporated to a sy rup .

A ddition o f e th an o l to th e syrup caused immediate c r y s t a l l i z a t io n ,

t o g ive th e oxide ^ 0 , y ie ld 560 mg ( 59^ ) , m.p. 151° , id e n t ic a l

w ith an a u th e n tic sample by t . l . c . , i . r . and n .m .r . s p e c tra , and

X -ray powder d i f f r a c t io n d a ta .

T . l . c . o f th e mother l iq u o rs showed th a t e s s e n t ia l ly a l l

o f th e oxide 30 had been removed by c r y s t a l l i z a t io n , b u t a com

ponent having th e m o b ility (R^ 0 . 51) of th e d ig lu c o sy l d is u lf id e

24 was p re s e n t . Column chrom atographic f r a c t io n a t io n o f th e mother

l iq u o rs gave th e d is u l f id e 2 4 , y ie ld 60 mg (6%), m.p. 140° , i d e n t i

c a l w ith an a u th e n tic sample by t . l . c . , i . r . and n .m .r . s p e c tra ,

and X -ray powder d i f f r a c t io n p a t te r n .

134

R eaction o f the su lfe n y l bromide 22 w ith 95% e th an o l to------------------ - — - - - - - — - A / M i i , ------ i , i — ■

g ive th e d is u l f id e 24 and th e mono-oxide 3 0 .--To th e su lfe n y la..— —... — ........wmbromide 22 (p repared from 2,317 g of 16) was added 95^ e thano lMW(40 ml) a t room tem pera tu re . The m ixture became c le a r a f t e r a

few min, and then became tu rb id and d ep o sited w h ite , f lu f f y n eed les .

A fte r 8 h r , th e re a c tio n m ixture was p rocessed as in th e preced ing

experim ent, to g ive the mono-oxide 30, y ie ld 1.239 g (59/>), m.p.

( a f t e r r e c r y s t a l l i z a t i o n from ho t e th an o l) 151- 152° , id e n t ic a l

w ith an a u th e n tic sample by mixed m .p ., i . r . and n .m .r . s p e c tra ,

and X-ray powder d i f f r a c t io n p a t te r n .

The mother l iq u o rs from th e re a c t io n con ta ined a s in g le

component, ch rom atograph ica lly id e n t ic a l w ith th e d is u l f id e 2 4 JMWt . l . c . o f th e i n i t i a l re a c tio n -p ro d u c t in d ic a te d th a t 2£ and £0

were p re s e n t in approxim ately equal amounts.

The fo rego ing experim ent and the p reced ing one were rep ea ted

se v e ra l t im e s , e i th e r by th e procedure d esc rib ed o r by f i l t e r i n g o f f

d i r e c t ly th e p roduct th a t c ry s ta l l iz e d from th e re a c t io n m ix tu re .

F req u en tly , th e e th a n o l- in so lu b le product ob ta in ed i n i t i a l l y had a

m elting p o in t low er than th a t o f th e m a to ria l ob ta ined a f t e r r e

c r y s t a l l i z a t io n from ho t e thanol} va lues o f 101-103° , 111- 113° ,

113-114°, 132-134°, and 138-139° were observed in d i f f e r e n t e x p e ri

m ents. In each in s ta n c e , the p ro d u ct was f r e e from th e d is u lf id e

£4 ( t . l . c . ) , and a f t e r re f lu x in g w ith e th a n o l, r e c r y s ta l l i z a t io n

gave the oxide ^0 having m.p. 152 . 5- 153° , w ith re c o v e rie s o f ~60

A second form o f ^ 0 ,having m.p. 157-158°, was a ls o encountered .

135

Brom ination of th e d is u lf id e £4 to give th e bromide j , . —

To a suspension of 24 (196 mg, 270 mmoles) in carbon te t r a c h lo r id e

(30 ml) was added bromine (1 .5 ml, 29 mmoles), and th e r e s u l ta n t

s o lu t io n was kep t f o r 23 h r a t 35°. The s o lu tio n was evaporated

to dryness a t 30° , carbon te t r a c h lo r id e was added t o , and evapo

r a te d from , th e re s id u e , and the l a t t e r was d isso lv ed in dry

c h lo ro fo rm 'd . The n .m .r . spectrum o f the s o lu t io n was id e n t ic a l92

w ith th a t o f th e te tra -O -ace ty l-a -D -g lu co p y ran o sy l bromide 1 ,

and th e in te g ra te d in te n s i t i e s of th e H-l s ig n a l (T’3 .2 5 , 2

4 .0 Hz) and o f th e ace ty l-g roup s ig n a ls were in th e r a t i o of 1 :12 .

T . l . c , o f th e s o lu tio n showed a p r in c ip a l component (ft 0 . 80 )

ch rom atog raph ica lly in d is tin g u ish a b le from JL} very minor s id e -

p ro d u c ts , having 0 . 4 2 , 0 . 31 , 0 . 2 9 , 0 . 2 0 , and 0 .1 were a ls o

p re s e n t .

B rom ination of the mono-oxide 30 to g ive th e bromide 1 .—' - ■ 1 ■ — ■■ ■ ■ MM> ■ ■■ ■ H- ■ MThe mono-oxide 30 (133 mg, 180 mmoles) was t r e a te d w ith bromine

(1 .5 ml» 29 mmoles) by e x a c tly the procedure used in th e p reced ing

experim ent, and id e n t ic a l r e s u l t s were ob ta ined .

T etra-O -acety l-p-D -g lucopyranosy lsu lfenam idobenzene (3 1 ) .—" . _1 T - i - r n. - . t «- i -

To a suspension o f the s u lfe n y l bromido 22 (3 .24 g , 7 .3 mmoles)

in carbon te t r a c h lo r id e (40 ml) was added a n i l in e (1 .4 m l, 1 5 .4

mmoles), and the m ixture was kep t f o r 1 h r a t room tem pera tu re .

Water (100 ml) was added to th e cloudy, ye llow , r e a c t io n m ix tu re ,

and th e m ixture was shaken. The o rganic la y e r was se p a ra te d ,

d r ie d (magnesium s u l f a t e ) , and evaporated to a sy ru p . The syrup

was d isso lv e d in e th e r (50 m l), and th e s o lu tio n was d eco lo rized

136

w ith carbon , concen tra ted to o n e -h a lf volume and petroleum e th e r

was added to opalescence. R e fr ig e ra tio n of th e s o lu tio n gave 31

as c o lo r le s s , f in e n eed les ; y ie ld 2 .7 6 g (83^), m .p. ( a f t e r one

r e c r y s t a l l i z a t i o n ) 116-117°, Ca ]p^ "330° (c 2 .A, ch loroform ); Rp

0 .85 homogeneous); 5.72 (OAc), 6 .2 3 , and 6 .70 urn ( a r y l ) ;Til S I X

\EtOH 288 ( e 2 ,000) (shoulder), 2V* (10 ,300), and 206 nm (13 ,900); max

n .m .r . d a ta , see Tables 8 and 9 ; X -ray powder d i f f r a c t io n d a ta :

12.53 w w , 10.13 vs (1) , 7 .16 w, 6 .40 w, 5.69 w, 5.31 s (2 ) ,

5.14- m, 4 .4 9 m, 4 .27 m, 3 .96 w, 3.67 m, and 3.52 m.

Anal. Calcd. fo r C ^ ^ N O g S : C, 52.73; H, 5 .53 ; N, 3 .0 8 ;

S , 7 .0 4 . Found: C, 52.78; H, 5 .45; N, 3 .2 8 ; S, 6 .8 5 .

T . l . c . o f th e mother l iq u o rs in d ic a te d th e p resence o f J l

and a minor component having th e m o b ility o f th e d ig lu c o sy l d i s u l

f id e 24.

4 “ (Dimethylaniino)phenyl t e t r a -O-a c e ty l - l - t h io - p -D-g luco-

pyranoside ( 3 2 ) .—A. From s u lfe n y l bromide. 22 and N ,N -dim ethyl-M M " — ■ i MM " , r " “

a n i l i n e . —To a suspension o f th e s u lfe n y l bromide 22 (2 .972 g ,

6 .7 mmoles) in carbon te t r a c h lo r id e (50 ml) was added N ,N-dim ethyl-

a n i l in e (2 ml, 15 .8 mmoles); th e m ixture tu rn ed g reen . A fte r 1 h r

a t room tem p era tu re , th e m ixture was evaporated (bath tem perature

4 3 ° ) , and th e r e s u l ta n t syrup was d isso lv ed in dichlorom ethane

(lOO m l). The so lu tio n was t r e a te d as d esc rib ed in th e fo rego ing

experim ent. The r e s u l ta n t , green syrup was d isso lv e d in e th e r , and

petro leum e th e r was added to opalescence. S evera l crops o f c ry s ta ls

were c o lle c te d ; th e f i r s t th r e e ( t o t a l y ie ld 1 .522 g , 62j£, m.p.

137

126-127°) were r e c r y s ta l l i z e d to g ive pure b i s ( t e t r a - 0 - a c e ty l - p -

D -glucopyranosyl) d is u l f id e 24 (1 ,348 g ) , m.p. 141-142 , in d is

tin g u is h a b le from an a u th e n tic sample*^ by t . l . c . , i . r . s p e c tra ,

and X -ray powder d i f f r a c t io n p a t te r n . The fo u rth and f i f t h c ry

s t a l f r a c t io n s , y ie ld 206 mg, were shown by t . l . c . to co n ta in 24

as a minor component, to g e th e r w ith a p r in c ip a l component (32)

having Rf 0 .8 1 . R e c ry s ta l l iz a t io n (tw ice) from e th an o l gave J2

a s c o lo r le s s n e ed le s , m .p. 150°, -5 4 .7 ° (c 0 .9 , chloroform )

[ l i t . 35 m.p. 150-151°, C®]20 "47° in “ ch lo ro fo rm )]; 0 .8 1 ;

Xmax 5 ,72 (°Ac)> 6*2^ and im â r y l^ J 276 12»5°°)

and 208 nm (16 ,900); n .m .r . d a ta , see T ables 8 and 9 ; X-ray

powder d i f f r a c t io n d a ta : 15.63 vw, 12.71 vw, 10.58 vs ( l , l ) ,

8 .48 vs (1 ,1 ) 6 .9 6 m, 5 .60 m, 5.27 m, 5 .00 m, 4 .74 w, 4 .51 w,

4 .3 9 s (2 ,2 ) , 4 .2 3 s ( 2 ,2 ) , and 4 .04 w.

Anal. C alcd. f o r 54.64; H, 6 .05 ; N, 2 .90 ;

S , 6 .6 3 . Found: C, 54 .87 ; H, 6 .1 1 ; N, 3 .2 1 ; S, 6 .9 6 .

B. From te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l bromide ( l ) and

p - d im ethylam inobenzeneth io l. —The procedure of Montgomery, R ich t- 35m yer, and Hudson was m odified . p-Dim ethylaminophenyl th io c y an a te

(18 g , 101 mmoles) in d ry e th e r (200 ml) was added w ith s t i r r i n g

to a suspension of l i th iu m aluminum hydride (4 .0 g , 105 mmoles) in

d ry e th e r (200 ml) th a t was m ain tained a t 0 ° , and s t i r r i n g was con

t in u e d fo r 45 min. The m ix ture was p rocessed by th e g en era l procedurif37

(137) L. H. Amundsen and L. S. N elson, J . Amer. Chem.

S o c ., 72, 242 (1951).

used f o r th e re d a c tio n of n i t r i l e s -with l ith iu m aluminum h y d ride .

The r e s u l ta n t , e th e re a l s o lu t io n was decanted from the gray-w hite

r e s id u e , and evaporated to g ive p-dim ethylam inobenzeneth io l (9*0 g ,

59 mmoles). The l a t t e r was n o t p u r i f ie d , because of th e ease w ith

which i t undergoes o x id a tiv e d im e riz a tio n , and i t was condensed

im m ediately w ith te tra -O -a c e ty l-a -D -g lu co p y ra n o sy l bromide ( l ,~ 31

20 g , 4 8 .6 mmoles) by th e g e n e ra l method o f Purves. E vaporation

of th e ye llow , tu r b id re a c tio n -m ix tu re gave a yellow sy ru p , which

was p a r t i t io n e d between dichlorornethane (100 ml) and w ater (100 m l).

The tu rb id m ixture was f i l t e r e d , and the o rgan ic phase was se p a ra te d ,

d r ie d (magnesium s u l f a te ) , and evaporated to g ive a yellow sy rup .

C ry s ta l l iz a t io n o f th e syrup from e th e r —petro leum e th e r gave 32;

y ie ld 5 .2 g (22$), m.p. ( a f t e r r e c r y s ta l l i z a t io n ) 149-150°, i d e n t i

c a l by mixed m .p ., i . r . spectrum , and X-ray powder d i f f r a c t io n p a tte rn

w ith 32 p repared by method A.

R eaction o f s u lfe n y l bromide 22 w ith N,N-d im e th y la n ilin e to

give p - ( dim othylam ino)phenyl t e t r a -O-a ce ty l-f t-D-g lucopyranosyl d i

s u lf id e (3 5 ) .—To a suspension o f 22 (3 .086 g , 7 .0 mmoles) in carbon

te t r a c h lo r id e (50 ml) was added N ,N -dim ethylan iline (2 m l, 15.8

mmoles), and th e m ixture was k ep t f o r 0 .5 h r a t 30°. The r e s u l ta n t

s o lu t io n was evaporated t o a syrup a t **90°, th e syrup was d isso lv e d

in dichlorornethane (100 m l), and th e so lu tio n was p rocessed as des

c rib e d fo r compound ^ 1 . The syrup ob ta ined showed m ajor components

having 0 .88 and 0*51 ( t . l . c . )• The m ixture was su b je c te d to

column chrom atography. The f i r s t f r a c t io n s e lu te d from th e column

were evaporated to a syrup th a t was d i s t i l l e d a t 180° (b a th ) /0 .1 5 to r r

139

t o g ive g.-bromo N ,N -d im ethy lan iline C^3); y ie ld 0.168 g , m.p.

52-54° [lit.-*-38,139 5 4 .7 ° ] , R£ 0 .9 9 (d e te c te d very slow ly)

(138) A. Weber, B e r ., 8 , 714 (1875).

(139) R. J . B. Marsden and L. E. S u tto n , J . Chem. S o c .,

599 (1936).

by s u l f u r i c a c id .

Anal. C alcd . fo r CgH^QBr N: C, 48 .02 ; H, 4 .8 9 ; B r, 39 .82 ;

K, 7 .0 0 . Found: C, 47 .85 ; H, 4 .8 9 ; B r, 39 .94 ; N, 7 .0 9 .

C ontinued e lu t io n o f th e column gave a ch rom atograph ica lly

homogeneous component, Rf 0 .8 8 , th a t c ry s ta l l iz e d from e thano l to

g ive th e d i s u l f id e 35 as p a le -y e llo w n e ed le s ; y ie ld 307 mg (8.555),

m .p. ( a f t e r one r e c r y s t a l l i z a t i o n ) 156-157°, -324° (c 1 .6 ,

c h lo ro fo rm ); R» 0 .9 ; 5.72 (OAc), 6 .2 5 , and 6.65 ^m ( a ry l ) ;m&xÊtOH 311 ( e l l f500), 268 (8 ,8 0 0 ), and 208 nm (12 ,700); n .m .r . max

d a ta , see T ables 8 and 9 ; X -ray powder d i f f r a c t io n d a ta : 16.50 w w ,

15 .22 w w , 10 .84 vs ( l ) , 8 .4 8 s (3 ,3 ) , 7 .76 u , 6 .76 w u , 6 .05 w,

5 .74 w w , 5 .4 0 m, 5 .09 m, 4 .80 s (2 ) , 4 .41 w, 4 .2 2 w, 4 .06 s ( 3 ,3 ) ,

3 .7 8 s ( 3 ,3 ) , and 3 .6 8 m.

A nal. C alcd. fo r C22H2gN09S2 : C, 51.25; H, 5 .67 ; N, 2 .7 2 ;

S , 1 2 .4 4 . Found: C, 51.06; H, 5 .78 ; K, 2 .9 7 ; S , 12 .13 .

Continued e lu t io n of th e column gave, f i r s t , a m ixture o f

components having R^ 0 .88 and 0 .5 0 , and th en th e component having R^

0 .50 a lo n e ; from th e l a t t e r f r a c t io n s , th e c r y s ta l l in e d ig lu c o sy l

d i s u l f id e was o b ta in ed , y ie ld 1 .11 g (44^), m .p. ( a f t e r

140

r e c r y s t a l l i z a t i o n from e th a n o l) 141- 142° , id e n t ic a l w ith a u th e n tic

24 by mixed m .p ., i . r . and n .m .r . s p e c t r a , and X -ray powder d i f -

f r a c t io n p a t te r n .

A second experim ent was perform ed under s im ila r c o n d itio n s ,

excep t th a t 5 .0 g (11.3 mmoles) o f 22 and 5 ml (39 .4 mmoles) o f

N ,N -d im ethy lan iline was used , and th e i n i t i a l syrupy p roduct was

h ea ted fo r “ 20 rain a t 1 0 5 ° /0 .2 t o r r . Coluran-chromatographic

f r a c t io n a t io n of th e p roduct gave, in th e e a r ly f r a c t io n s , b i s -

(p-dim ethylam inoplienyl) d is u l f id e ( 34 )» i s o la te d c r y s ta l l in e from

e th e r j y ie ld 566 mg, m.p. 1 1 7 .5 -1 1 8 .5 ° [ l i t . ^ ® m .p. 118°].

(140) V. Merz and V, W eith, B e r ., ! £ , 1570 (1886).

A nal. C alcd. fo r C16 I 0 K2 % ! c > 63 .11 ; H, 6.62} N, 9.20}

S , 21 .06 . Found: C, 63.18} H, 6.56} N, 9 .2 0 ; S, 2 0 .9 8 .

F u rth e r e lu t io n o f th e column gave f r a c t io n s th a t con ta ined t e t r a -

O -ace ty l-a -D -g lucopyranosy l bromide ( l ) , y ie ld 2 .155 g (46^),

id e n t i c a l w ith an a u th e n tic sample by i . r . and n .m .r . s p e c tra .

The next compound to be e lu te d from th e column was th e

a r y l g ly co sy l d is u l f id e 3 5 , y ie ld 324 xng (6$ ) , id e n t i c a l w ith th e

p roduct ob ta ined in th e p re p a ra tio n a lre a d y d e sc r ib e d . Subsequent

f r a c t io n s y ie ld e d th e d ig ly c o sy l d is u l f id e 2 4 , y ie ld 446 mg ( 5/6) ,

m .p. 141-142°.

In a t h i r d experim en t, th e r e a c t io n between 22 (1 .17 g)

and 2 e q u iv a le n ts o f N ,N -d im ethy lanIline was allow ed to proceed

f o r 60 h r a t 3 0 ° , and th e p roduct was i s o la te d w ithou t h e a tin g

141

I t above 4 0 ° . F ra c t io n a t io n gave th e a ry l g ly co sy l m onosulfide

32 (188 mg, 15$), and th e d ig ly c o sy l d is u lf id e 24 (579 mg, 6o£).

R eaction o f s u lfe n y l bromide 22 w ith (a) acetophenone,' x J - i - n - n - 1- -1 ' " '

(b ) a ce to n e , (c) cyclohexanone, and (d) p h en o l. —Suspensions o f

th e su lfe n y l bromide 22 in carbon te t r a c h lo r id e were t r e a te d , in

se p a ra te experim en ts, w ith th e fo llow ing ke tones or e n o ls , in

th e m olar p ro p o rtio n s in d ic a te d ( r e l a t iv e t o 0 .1 o f 22 ) : a c e to

phenone (l.O m o le), acetone (4 .4 m o les), cyclohexanone (l.O m ole),

and phenol ( l . l m o les). The r e a c t io n m ixture was k e p t fo r 1-3 h r

a t room tem p era tu re , and th e n p rocessed by th e g e n e ra l procedures

used fo r i s o la t in g coupling p ro d u c ts formed from 22, In each

o f the fo u r experim en ts, th e p r in c ip a l p ro d u c t, i s o la te d c r y s t a l

l in e in 70 , 63, 76 , and 15% y ie ld s , r e s p e c t iv e ly , was b i s ( t e t r a - 0 -

ace ty l-p -D -g lu co p y ran o sy l) d is u l f id e 24, m .p. 142-143°, id e n t ic a l

w ith an a u th e n tic sample by mixed m .p ., i . r , spectrum , and X -ray

powder d i f f r a c t io n d a ta .

Phenyl t r i -O-a c e ty l- f t-D-xy lopyranosy l d is u l f id e (39) from

1 -th io -p -D -xy lopy ranose t e t r a a c e t a t e (1 5 ) .—A suspension o f 1 5 .

(1.867 g , 5.6 mmoles) in carbon te t r a c h lo r id e (50 ml) was cooled

to about - 10° and bromine (2 ml) in carbon te t r a c h lo r id e (8 ml)

was added to th e coo led su sp en s io n . V o la ti le m a te r ia ls were im

m ed ia te ly removed on .a r o ta r y ev ap o ra to r a t ~30° / c l 0 t o r r , to

g iv e a s e ro irc ry s ta l l in e , ye llow re s id u e . T . l . c . o f a carbon t e t r a

c h lo r id e s o lu tio n (50 ml) o f th e re s id u e showed th re e components in

about equal in te n s i t y , Rp 0 .7 6 , 0 .5 0 , and 0 .4 3 . B enzeneth io l

U2

( l ml) was added to th e r e a c t io n m ixture and an immediate c o lo r

change, from yellow t o c o lo r le s s , was observed. T . l . c . of th e

s o lu t io n , a f t e r 10 min a t room tem p era tu re , showed a m ajor com

p o n e n t, Rf 0 .8 9 , and th re e minor components, Rr* 1 .0 0 , 0 .5 0 , and

0 .4 3 . The s o lu t io n was k ep t f o r 1 h r a t room tem p era tu re , washed

w ith aqueous sodium hydrogen carbonate (100 m l), d r ie d (magnesium

s u l f a te ) ,a n d evapora ted to a sy rup . An n .m .r . spectrum of a

ch lo ro fo rm -d s o lu t io n o f th e crude p roduct showed a lo w -f ie ld

d o u b le t , T3 . 4 0 , J-^ 2 [ tr i-O -a c e ty l-a -D -x y lo p y ra n o sy l bromide

(4 ) , l i t . 92 T 3 .3 0 , J l j 2 4 .0 Hz], T ~ 2 .25 -2 .90 (a ry l p ro to n s ) ,

7 ~ 4 .2 5 -5 .4 0 (complex m u l t ip le t ) , T ~ 5 .6 5 -6 .7 0 (complex m u lt ip le t ) ,

and T 7 .94 , 7 .9 8 ( s in g le t s , OAc). The r a t i o o f th e in te g ra te d i n

t e n s i t y of th e lo w - f ie ld d oub le t to th e a c e ty l s ig n a l was 1 :1 6 .

A carbon te t r a c h lo r id e s o lu t io n of th e p roduct was kep t 2 days a t

room tem p era tu re and evapo ra ted to a sy rup . E vaporation was con

t in u e d u n t i l th e w ater b a th tem pera tu re reached 70°. The b la c k ,

syrupy re s id u e was d is so lv e d in carbon te t r a c h lo r id e (75 m l),

aqueous sodium hydrogen carbonate (75 ml) was added t o th e s o lu t io n ,

and th e heterogeneous m ix ture was k ep t f o r 24 h r a t room tem pera tu re .

The phases were se p a ra te d and th e organ ic phase was d r ie d (magnesium

s u l f a t e ) and ev apo ra ted to a sy rup . T . l . c . o f th e syrup rev ea led

th re e m ajor com ponents, Rc 0 . 8 9 , 0 . 59 , and 0 .17 (p o in t o f a p p li

c a tio n ) and two minor components, Rf 1 .0 0 and 0 .2 8 . The syrup was

su b je c te d to column chromatography and th e component, Rf 0 ,8 9 was

c o l le c te d , ev ap o ra ted to a sy ru p ,m d c ry s ta l l i z e d from a sm all

volume o f e th e r —petro leum e th e r to g ive a p roduct fo rm ula ted as

143

phenyl tr i-O -ace ty l-p -D -x y lo p y ran o sy l d is u lf id e (39) , y ie ld

69,6 mg, 0 ,17 mmoles (3/5), D eco lon iza tion (a c tiv a te d charcoa l)

of an e th e r so lu tio n o f th e product and r e c r y s t l l i z a t io n gave 39

as f in e , white n e e d le s , m.p. 120-121° , “242° (c 1 , 2 , c h lo ro

form ); 5.72 (OAc) and 6 .7 7 , 6 .96 pm ( I r y l ) ; X ^ H 288 ( ^3 ,500)

(sh o u ld e r) , 238 (6 , 500) , and 200 nm (1 0 , 000) ; n .ra .r . d a ta see

Tables 8 and 9 and F igure 2 ; X-ray powder d i f f r a c t io n data :

13.63 w, 11.94 in, 10.64 s ( l ) , 8.05 s (2 ) , 6 .98 vw, 5.33 s (3 ,3 ) ,

4 .76 s (3 ,3 ) , 4 .45 m, 4 .19 m, 3 .99 m, 3 .79 u , 3 .64 w, 3.45 s (4 ) .)

A nal. Calcd. fo r ^ 78200^82 ! C, 50.98; H, 5 .03 ; S, 16 .01 .

Found: C, 51.23; H, 5 .46 ; S , 15 .86 .72 oIn a b r i e f re p o r t Horton and M ille r gave f o r ^9 m .p. 122 ,

[ a ] ^ - 250° (ch lo ro form ).

The re a c tio n was rep ea ted w ith 2.04-2 g (6 .1 mmoles) o f

however, th e decom position procedure was e lim in a ted and th e p ro

duct was worked up 1 h r a f t e r a d d it io n of b en zen e th io l as describ ed

in th e fo rego ing experim ent. The syrupy product was c ry s ta l l iz e d

from e th e r to g ive tr i-O -a c e ty l-a -D -x y lo p y ra n o sy l bromide

y ie ld 1.262 g , 3 .7 mmoles (61$ ), The p roduct had m .p. 100-102°

[lit.95,96 102° ] . The n .m .r . d a ta were c o n s is te n t w ith those

02p rev io u s ly re p o r te d . 7

Benzyl t r i -O-a c e ty l -p -D-xylopyranosy l d is u l f id e (40) from

1-th io -p -D -xy lopyranose t e t r a a c e ta te (1 5 ) .—A suspension of 15.

(557 mg, 1 .67 mmoles) in carbon te t r a c h lo r id e (30 ml) was

brom inated under th e c o n d itio n s d esc rib ed in th e fo rego ing

144

experim ent and a - to lu e n e th io l (0 .5 ml) was added to a carbon

te t r a c h lo r id e so lu tio n (50 ml) of th e crude brom ination p ro d u c t.

A fte r 10 min a t room tem pera tu re , t . l . c . o f th e re a c tio n m ixture

showed a m ajor component, R^ 0 .86 and th re e minor components, Rp

0 .5 1 , 0 .4 1 , and 0 .3 2 . A fte r 1 h r a t room tem perature the so lu tio n

was evaporated to a sy rup , which was d isso lv ed in dichlorom ethane

(60 m l). The s o lu tio n was washed w ith aqueous sodium hydrogen

carbonate (50 m l), d r ie d (magnesium s u l f a te ) and evaporated to a

sy rup . Column chromatography o f th e p roduct gave the component

having Rp 0 .86 as a sy ru p , th a t c ry s ta l l iz e d from e th e r—petroleum

e th e r to g ive benzyl 2 ,3 ,4 - tr i-O -a c e ty l-p -D -x y lo p y ra n o sy l d is u lf id e

(40) as w hite n eed le s , y ie ld 125 mg, 0 .30 mmoles (18$). Two r e

c ry s ta l l i z a t io n s from e th e r—-petroleum e th e r gave th e a n a ly tic a l

sam ple, m .p. 126°, [ c ] D -229° (c 0 .8 , ch loroform ); XKBr 5.72 (oAc),insoc6 .76 and 6 .90 pm (aryl)"; *2t0H 270 ( e 1 ,5 0 0 ), 220 (8,500) (sh o u ld e r) ,maxand 209 nm (10 ,000); n .m .r . d a ta , see Tables 8 and 9 ; X-ray

powder d i f f r a c t io n d a ta : 10 .10 m, 8 .54 s (3 ) , 6 .55 w, 5.96 w,

5.45 s ( 2 ,2 ) , 5.02 s ( l ) , 4 .78 s (2 ,2 ) , 4 .39 vvw, 4 .12 m, 3.97 vyw,

3 .7 4 w, 3 .41 m, 3 .26 m, 3 .12 w.

Anal. Calcd. f o r C j^ E ^ O ^ : C, 52.16; H, 5 .35; S , 15 .47 .

Found: C, 51 .98 ; H, 5 .32 ; S, 15 .20 .

Phenyl t r i - Q-acetyl-OT-L-arab inopyranosy l d is u lf id e (41)

from 1 -th io -a -L -a rab in o p y ran o se te t r a a c e ta te (1 4 ) .—A so lu tio n■ 1 ■■ in- 1 1 11 ■ ■ — — - ------------------ -----------

14 (1.977 g , 5 .9 mmoles) in carbon te t r a c h lo r id e (50 ml) was

oooled to about -10° and t r e a te d by th e procedure d esc rib ed fo r

th e b rom ination of 1 -th io -p -D -xy lopyranose t e t r a a c e ta te ( l j j ) .

145

The p roduct a f t e r evapo ra tion was a yellow sy rup . T . l . c . of a

carbon te t r a c h lo r id e s o lu tio n (50 ml) o f the syrup showed th re e

components of approxim ately equal in te n s i ty , Rp 0 .7 2 , 0 .5 1 , and

0 .44 . B enzeneth io l ( l ml) was added to th e carbon te t r a c h lo r id e

so lu tio n and th e r e a c t io n m ixture was t r e a te d e x a c tly as described

fo r th e p re p a ra tio n of the phenyl x y lo sy l d is u lf id e 39. An n .m .r .

spectrum (60 MHz) of a s o lu tio n of the crude syrup in ch loroform -d

showed a lo w -f ie ld d o u b le t, ? 3 .2 9 (H -l o f t r i-O -a c e ty l-p -L -92arab inopyranosy l bromide (3) [ l i t . "*3.25 fo r th e p-D isom er),

T "2 .2 5 -2 .9 5 (a ry l p ro to n s ) , T ~ 4 .4 -5 .4 (complex m u lt ip le t ) ,

T *“5 .65 -6 .55 (complex m u l t ip le t ) , and T 7 .8 9 , 7 .9 5 , 7 .99 (m u lt ip le t ,

OAc). The syrup was d isso lv e d in carbon te t r a c h lo r id e and the

so lu t io n was t r e a te d as d e sc rib ed fo r th e p re p a ra tio n of th e phenyl

x y lo sy l d is u lf id e 39. T . l . c . o f th e dark syrup showed a major

component, R , 0 .89 and fo u r m inor components, Rp 0 .5 5 , 0 .4 8 , 0 .2 8 ,

and 0 .1 8 . The p roduct was f i l t e r e d th rough s i l i c a g e l w ith s o l

vent A as e lu e n t; however, no s e p a ra t io n occu rred . The product was

c ry s ta l l iz e d from e th e r —petroleum e th e r to g ive 0.564 g o f f lu f f y ,

white n e ed le s . T . l . c . showed only a s in g le component, Rp 0 .89 .

An n .m .r . spectrum (100 MHz) o f a s o lu t io n of tho p roduct in

chloroform -d showed th e compound to be impure by an unexpectedly

la rg e number o f s ig n a ls f o r H-5 , 5 ' , T5 . 85- 6 .16 (8 - l in e m u lt ip le t ) ,

T 6.29-6 .65 (7 - l in e m u l t ip le t ) . A d o u b le t, T 5 .29 , 2 was

assig n ed to K-l of phenyl 2 ,3 ,4 - tr i-O -a c e ty l-o -L -a ra b in o p y ra n o sy l

d is u lf id e (41 )J however, th e s ig n a l had an in te n s i ty to o g re a t

f o r a s in g le p ro to n . An n .m .r . spectrum (100 MHz) of a s o lu tio n

of the p roduct in benzene-d^ showed th e p resence o f two d o u b le ts ,

'•’5*33 and 5 .4 5 , each having a spacing of 7 .8 Hz. The m u lt ip le ts

a ss ig n e d to H-5, 5' fo r th e chloroform -d s o lu t io n were observed

as narrow er m u lt ip le ts w ith benzene-d^ as s o lv e n t, *^6.15-6.47

(m u ltip le t) and **6 .8 5 -7 .05 (m u lt ip le t ) .

The p roduct was allow ed to c r y s ta l l i z e im com pletely from

e th a n o l, and pure phenyl tr i-O -a c e ty l-a -L -a ra b in o p y ra n o sy l d i

s u l f id e (£1 ) was o b ta in ed , y ie ld 8 3 .6 mg, 0 .2 1 mmoles (4^ ) , m.p.

124°, [a ]g 8 -171° (c 0 . 8 , ch lo ro fo rm ); 5 .72 (OAc), 6 .77 and

6 .9 6 pm ( a r y l ) ; 288 (e 2 ,300) (sh o u ld e r) , 238 (9 , 000) , and

200 nm (16 ,000); n .m .r . d a ta : soe Tables 8 and 9 and F igure 4- j

X -ray powder d i f f r a c t io n d a ta : 10.23 m, 9 .22 m, 7 .57 m, 7 .70 w,

6 .91 vw, 5.77 m, 5 .49 m, 5 .05 s ( l ) , 4 .42 m, 4 .1 9 m, 4 .0 6 m.

Anal. Calcd. fo r C17H2Q07 S2 : C, 50.98; H, 5 .03 ; S, 16 .01 .

Found: C, 50.78; H, 5 .05 ; S, 16 .22 .

T . l . c , o f th e r e s id u a l s o lu t io n showed component, 0 .8 9 ,

as th e m ajor p ro d u c t; however, f u r th e r c r y s t a l l i z a t io n d id not

occu r. The re a c t io n was rep e a te d w ith 2.032 g , 6 .1 mmoles o f 2 £ ,

b u t the decom position procedure was e lim in a ted and th e product was

is o la te d 1 h r a f t e r th e a d d it io n o f b e n ze n e th io l. A fte r th e u su a l

work-up th e o rgan ic s o lu t io n was evaporated to g ive a sy ru p , th a t

c r y s ta l l i z e d from e th e r to y ie ld c o lo r le s s n eed les o f t r i - 0 -a c e ty l '

p -L -arab inopyranosy l bromide (3 ) , y ie ld 1.257 g , 3 .7 mmoles (6 l £ ) ,

m .p. 138-139° [ l i t . 94 139°],, The n .m .r . d a ta f o r a s o lu tio n

of th e product wore c o n s is te n t w ith th o se p re v io u s ly re p o rte d f o r Q2th e p-D isom er.

147

Phenyl te tra -O -a c e ty l-g -D -g a lac to p y ran o sy l d is u lf id e (A3)

from 1 -th io -p -D -g a lac to p y ran o se p e n ta a c e ta te (17)*—Compound JL7

(1.854 g , 4 .56 mmoles) was brom inated a t low tem pera tu re a s d es-

sc r lb e d f o r the p re p a ra tio n of th e pbenyl x y lo sy l d is u lf id e 39

and b en zen e th io l ( l ml) was added. T . l . c . o f th e re a c t io n m ixture

'1 0 min a f t e r th e a d d itio n of b en zen e th io l showed th e re a c tio n

m ixture to co n ta in th re e components o f approxim ately equal in te n

s i t y , Rj, 0 .8 9 , 0 .83 ( s t a r t in g m a te r ia l ) , and O.6 3 . The re a c tio n

was rep e a te d w ith 17 (2 .030 g , 4 .9 9 mmoles); however, th e carbon

te t r a c h lo r id e s o lu tio n o f 17 was no t cooled b e fo re b rom ination .

Bromine (2 ml) in carbon te t r a c h lo r id e (8 ml) was added to the

s o lu t io n , which was kep t fo r *“30 sec a t room tem pera tu re b e fo re

e v a p o ra tio n . A fte r ra p id ev ap o ra tio n of the v o l a t i l e components

and d is s o lu t io n o f the syrupy p roduct in carbon te t r a c h lo r id e (50 m l),

t . l . c . showed th re e minor components, R , 0 .9 1 , O.83 , and 0 .4 0 , and

a major component, R^ 0 .6 4 . B enzeneth io l ( l ml) was added to th e

s o lu t io n and a f t e r 10 min a t room tem perature t . l . c . showed th e

same th re e components d e sc rib ed f o r th e low tem pera tu re experim ent;

however, th e component, O.83 , was o f d im inished in te n s i ty . A fte r

1 h r a t room tem p era tu re , th e r e a c t io n m ixture was worked up in th e

u su a l manner and an n .m .r . spectrum (60 MHz) o f th e crude product

in ch lo ro fo i’m-d showed a complex m u l t ip le t , *>’2 .2 6 -3 .1 0 ( a r y l ) ,

m u lt ip le ts T4 . 3 9 - 5 . 1 3 and 75 .23- 6 .2 5 , a s in g le t a t T 6.47 , a s in g le t

a t T7.58 (SAc), and a complex m u lt ip le t cen te red a t T **7.95. No

lo w -f ie ld doub let^2 was observed a t T3 .2 3 th a t would in d ic a te th e

048

presence of te tra -O -a c e ty l-a -D -g a la c to p y ra n o sy l bromide (2 ) .

The syrupy p roduct was d isso lv e d in carbon te t r a c h lo r id e and

t r e a te d as d esc rib ed in the p re p a ra tio n of the phenyl x y lo sy l

d is u lf id e 39. however, no decom position was observed , A p o rtio nMM * 9

of th e compound having 0 .9 1 , was se p a ra ted by column chromatog

raphy. Complete se p a ra tio n o f th e components R , 0 .91 and 0.83 was

not o b ta in ed . The f r a c t io n s t h a t co n ta in ed on ly component,

0.91 were combined and evaporated to a syrup ,w hich c r y s ta l l i s e d

as w h ite , s to u t need les to g ive a p roduct fo rm ula ted as phenyl

te tra -O -a c o ty l-p -D -g a la c to p y ran o sy l d is u lf id e (4 3 ) , y ie ld 161 mg,

0.3 mmole (6%). The p roduct had m.p. 126-127° ( a f t e r one r e c r y s ta l

l i z a t i o n from e th e r ) , -155° (c 1 .4 , ch lo ro fo rm ); 5.75

(0AC) , 6 .8 0 , 6 .97 pm ( a r y l ) ; 288 ( 6 2,800) (sh o u ld e r) ; 238

(7 ,7 0 0 ), and 200 nm (1 5 ,5 0 0 ); n .m .r . d a ta : see Tables 8 and 9 and

Figure h ; X -ray powder d i f f r a c t io n d a ta : 10.52 s ( 3 ,3 ) , 7.03 s ( l ) ,

6.07 s (2 ,2 ) , 5.47 m, 5 .07 m, 4 .7 0 s (4 ) , 4 .37 m, 4 .24 m, 4 .05 s

(3 ,3 ) , 3 .87 w, 3 .67 s ( 2 ,2 ) , 3 .5 0 s (3 , 3 ) .

Anal. Calcd. f o r C ^ H ^ O ^ : C, 50.83; H, 5 .12 ; S, 13 .57 .

Found: C, 50 .69 ; H, 5 .2 4 ; S, 13 .19 .

Phenyl te tra -O -a c e ty l-p -D -g lu c o p y ran o sy l d is u l f id e (23)r S ■l ' ' 1 ■"« ■ 1 1 1 " ' ■ 1 1 ' ■ MMfrom 2 ,3 ,4 ,6 - t e t r a - Q -a ce ty l-l-S -b en zo y l-l-th io -ft-D -g lu co p y ra n o se

( 2 9 ) .—Bromine ( l ml) in carbon te tr a c h lo r id e (9 ml) was added toMM '

compound 22 (556 mg, 1 .2 mmoles) in carbon te t r a c h lo r id e (50 m l).

The re a c t io n m ixture was k ep t f o r 3 min a t room tem pera tu re befo re

rap id ev ap o ra tio n of v o l a t i l e components to give a yellow c r y s ta l

l in e re s id u e . The re s id u e was d is so lv e d in carbon te t r a c h lo r id e

(50 ml) and b en zen e th io l (0 .3 ml) was added, T . l . c . o f th e re a c

t io n m ixture a f t e r 10 min a t room tem peratu re showed 2 components,

0 .8 9 (major) and 0 .5 6 . A fte r 1 hr a t room tem p era tu re , th e

r e a c t io n m ixture was washed w ith a s a tu ra te d s o lu t io n o f aqueous

sodium hydrogen ca rb o n a te , d r ie d (magnesium s u l f a t e ) , and evapo

ra te d t o a sy rup , th a t c r y s ta l l i z e d from e th e r—petro leum e th e r

t o y ie ld phenyl te tra -O -a c e ty l-p -D -g lu c o p y ran o sy l d is u l f id e (2 3 ),

165 mg, 0 .35 mmole (2 9 $ ), in two c ry s ta l c ro p s . The product73had m .p. 121-122° ( a f t e r 1 r e c r y s t a l l i z a t i o n from e th a n o l) , [ l i t .

m.p. 123-124°]. The p roduct was id e n t ic a l to an a u th e n tic sample

by X -ray powder d i f f r a c t io n p a t te r n and by comparison of n .m .r .73s p e c t r a l d a ta fo r a ch lo ro fo rm -d s o lu t io n .

T . l . c . o f th e mother l iq u o rs a f t e r 5 days showed a m ixture

of components, 0 .89 (m ajo r), 0 .7 0 , 0 .6 3 , 0 .5 6 , 0 .3 2 , and 0.19

(m ajo r, p o in t o f a p p lic a t io n ) .

B rom ination o f 1 - th io - a - D-glucopyranose p e n ta a c e ta te (18)

and tra p p in g o f th e re a c tio n p roduct w ith b e n z e n e th io l. —Compound

18 (360 mg, 0 .9 mmole) was suspended in carbon te t r a c h lo r id e and

bromine (~1 ml) was added to th e suspension a t room tem p era tu re .

V o la ti le m a te r ia ls were r a p id ly evaporated to g ive a yellow

c r y s ta l l in e r e s id u e . The re s id u e l o s t weight on th e ba lance pan ,

thus a ttem pt a t f u r th e r c h a ra c te r iz a t io n was te rm in a te d . The

re s id u e was d isso lv e d in carbon te t r a c h lo r id e (50 ml) and benzene

th io l (0 .3 ml) was added. The re a c t io n m ixture was k ep t 1 h r a t

room tem pera tu re and th e work-up was i n th e u su a l manner. The

re a c tio n p ro d u c t, a sy ru p , was evaporated tw ice from carbon

150

te t r a c h lo r id e (50 m l). An n .m .r . spectrum of a s o lu tio n of the

syrup in chloroform -d showed a m u lt ip le t , T 2.25- 2 .75 (a ry l p ro to n s ) ,

7 ~3.65 (H -l o f 1 8 ), 74 .03 (low in te n s i ty doublet w ith a spacing of

*“6 .0 Hz, 74,.20 d o u b le t,w ith a spacing of *“5 .8 Hz), 7 4 .4 -5 .1

(m u lt ip le t ) , T **5.4-6.5 ( m u lt ip le t ) , 7 7 . 54. (SAc), 7 *'7.90 (m u lti

p l e t , OAc). The r a t i o o f th e in te g ra te d in te n s i ty o f the S -a c e ty l

s ig n a l to th e 0 -a c e ty l s ig n a l in d ic a te d th a t **40$ o f th e s t a r t i n g

m a te r ia l was p re s e n t , T . l . c . o f th e product showed two major

components, 0 .86 and 0 .8 0 , and fo u r minor components, 0 .6 6 ,

0 .5 4 , 0 .2 8 , and 0 .21 (p o in t o f a p p l ic a t io n ) . The component, R^

0 .80 corresponded to 18. The f a s t e r moving components, R„ 0.86

and 0.83 were se p a ra te d from th e m ixture w ith th e use o f column

chrom atography. An u n su ccessfu l a ttem pt was made t c se p a ra te th e se

components by f r a c t io n a l c r y s t a l l i z a t io n from e th a n o l. A m ixture

o f the compounds was ob ta ined as in d ic a te d by th e rw nr. spectrum

(lOO MHz) of th e p roduct in a chloroform -.^ s o lu t io n . See F igure 5

fo r th e n .m .r . spectrum o f th e crude p ro d u c t. F urther a ttem pts

a t p u r i f ic a t io n o f th e se compounds were u n su c ce ss fu l.

EXPERIMENTAL - PART B

P h o to ly s is p rocedu re . —The u l t r a v io l e t source fo r

p h o to ly s is experim ents was a m ercury-arc lamp (Hanovia Type L,

Model 697A, Hanovia Lamp D iv is io n , Engelhard Hanovia I n c , ,

Newark, N. J . ) , The lamp was equipped w ith a w ater-coo led ,

q u a rtz im m ersion-w ell (Hanovia Model 194-31) flnd th e assembly

was mounted in a Pyrex re a c t io n v e s s e l . P h o to ly s is was e ffe c te d

w ith u n f i l te r e d l i g h t and th e so lu tio n s undergoing p h o to ly s is

were s t i r r e d w ith a m agnetic s t i r r i n g b a r and th e appara tus was

c o n tin u a lly f lu sh e d w ith n itro g e n . The p h o to ly s is so lv e n t was

methanol (S pectro g rade , Eastman O rganic Chemicals, R ochester,

Neu Y ork), A ll N ,N -dim ethyltbiocarbam ates were su b je c ted to

column chromatography befo re p h o to ly s is to ensure p u r i ty . A ll

o th er g en era l p rocedures were as d esc rib ed fo r G eneral methods,,

P a rt A.

P re p a ra tio n o f 3-0 -d im ethy lth iocarbam oyl- 1 ,2 ; 5 ,6 -d i-O-

isopropy lidene-a-D -g lucopyranose (4 6 ) .—Compound 46 was p repared

accord ing to th e method o f Horton and P r ih a r .^ A s o lu t io n of

l ,2 :5 ,6 -d i-0 - iso p ro p y lid e n e -a -D -g lu c o fu ra n o se 11^ (50, 25 .0 g , 96.0— wiw 1

mmoles) in N,N-dimethylformamide (200 ml) was t r e a te d w ith 3 .30 g

o f a 61% sodium hydride d isp e rs io n in m ineral o i l (M etal H ydrides,

I n c . , B everly , M assach u se tts) . The m ixture was coo led and main

ta in e d below 2 0 ° , w hile being s t i r r e d under a n itro g e n atmosphere

151

3.52

fo r 1 h r . To th e s t i r r e d m ixture was added dim ethylthiocarbam oyl

ch lo rid e (12 ,3 g ) . The m ixture was s t i r r e d 1 .5 h r and poured

onto ic e and w ater (~5Q0 g) w ith v igorous s t i r r i n g . S o lid product

(27 .0 g , 77 .6 mmoles, 80 .8%) sep a ra ted and was r e c r y s ta l l iz e d from

e th an o l to g iv e 46 , y ie ld 18 .0 g , 51 .8 mmoles (54.0/6), m.p. 105-

106°, [o]** -6 2 .6 ° (c 1 .3 , chloroform ) [ l i t . 1 m.p. 1 0 5 .5 ° , [ a ]22

-70° (c 2 , ch lo ro fo rm )]. The n .m .r . d a ta (60 KHz) were c o n s is te n t

w ith those p re v io u s ly r e p o r te d .1

P re p a ra tio n of l ,6 -a n h y d ro -4 -0 -d im ethy lth iocarbam oyl-2 ,3 -

O-isopropylidene-p-D-m annopyranose (4 7 ) .—Compound 47 was p repared■ ' ■ | | * ' | 1 ■ » . , — '■ ■■ ■■■ iwm129from l,6 -anhydro-2 ,3-0-isopropylidene-p-D -m annopyranose accord ing

to th e method of Horton and P rih ar^ by Diana M. W illiams (N ational

Science Foundation Undergraduate R esearch P a r t ic ip a n t , Summer, 1967).

The n .m .r . d a ta (A-60 n .m .r ; spectrom eter) were c o n s is te n t w ith1 28 those p re v io u s ly re p o rte d , m.p. 136-137° [c ]^ -8 3 .0 ° (c 1 .080 ,

chloroform ) [ l i t . m.p. 135°, [a ]^ 0 -6 4 .5 ° (c 2 , ch lo ro fo rm )].

P re p a ra tio n o f 6 -0 -d ira e th y lth io c a rb a m o y l- l,2 :3 ,4 -d l-0-

isop ropy lidene-a-D -galac topyranose ( 4 8 ) .--Compound 48 was p repared■ " ” " ' ' ' — i - i ■ I.. ■ .1 ■ MA#

from l,2 :3 ,4 -d i-0 -iso p ro p y lid e n e -o -D -g a la c to p y ra n o se (57) (A ldrich

Chemical Company, I n c . , Milwaukee, W isconsin) according to th e

method of Horton and P r ih a r .1 Compound 57 (14 .0 g , 53.8 mmoles)

was d isso lv e d in N,N-dimethylformamide (200 ml) and t r e a te d w ith

a 6 l£ sodium hydride d isp e rs io n (1 .94 g) and th en w ith d im e th y lth io

carbamoyl c h lo rid e (6.65 g) by the procedure used in th e p re p a ra tio n

o f 46 . The crude y ie ld o f 48 was 14 .5 g , 41.7rcmoles- 7 7 .5£. Re-

c r y s t a l l i z a t io n from e th an o l gave 12 .0 g , 34.5mmoles (64.156),

153

m .p. 90-91°, Ca ] ^ “59 .4° (c 3 .1 , ch lo ro fo rm ). The n .m .r . da ta

were c o n s is te n t w ith those re p o rte d p re v io u s ly .1 [Lit.'* ' m .p.

88-89°, [o ]^ ° -4-7.3 (c 2 , ch lo ro fo rm )].

P re p a ra tio n of l , 2 : 5 ,6 - d i -0 “iso p ro p y lid en e -3 -0 -p - t o i y l -

s u lfo n y l-a -D-glucofuranose (5 3 ) .—To a s o lu t io n o f l ,2 :5 ,6 - d i - £ -

isop ropy lidene-c-D -g luco fu ranose (50, 25 .0 g , 96 .0 mmoles) in

p y rid in e (250 ml) was added j)- to lu en e su lfo n y l c h lo rid e (21 .0 g,

110 mmoles). A fte r 2 days a t room tem pera tu re , w ater (25 ml) was

added and s t i r r i n g was con tinued f o r an a d d it io n a l 1 h r . The reac

t io n m ixture was poured onto v ig o ro u s ly s t i r r e d ic e and w ater

(~400 g) and th e c r y s ta l l in e p roduct was f i l t e r e d , uashed w ith

w ater, and r e c r y s ta l l i z e d from e th an o l to g ive f in e , w hite need les

in two c ro p s , y ie ld 28 .0 g , 67 .5 mmoles (70.320» m.p. 120-121°,

[a ]28 -6 8 .8 ° (c 1 .0 3 , chloroform ) [ l i t . 120 m.p. 120-121°, [ a ] D

-8 1 .7 ° (1 ,1 ,2 ,2 - te t r a c h lo ro e th a n e ) ] , The n .m .r . d a ta (60 MHz

n .m .r , sp ec tro m eter) were c o n s is te n t w ith those re p o rte d by21Je w e ll, H orton, and P r ih a r .

P re p a ra tio n of 3-deoxy-3“h y d ra z in o - l ,2 :5 ,6 -d i-0 - iso p ro p y li-

dene-a-D -allo fu ranose ( 5 4 ) .--Compound 54 was p repared accord ing to ™ " — ' '' "' " ' “ ' ’th e method o f Coxon and Hough12 - and Uolfrom and co -w orkers.12^

To 97+^ anhydrous hydrazine (100 ml) was added l ,2 :5 ,6 - d i - 0 -

iso p ro p y lid en e-3 -Q -p -to ly lsu lfo n y l-a -D -g lu co fu ran o se (53, 2 5 .0 g,

60.3 mmoles) and th e re a c t io n m ixture was re flu x e d under a stream

o f n itro g e n f o r 40 h r . The s o lu t io n was cooled and e x tra c te d w ith

th re e 100-ml p o r tio n s o f p e ro x id e -fre e e th e r . The combined o r

ganic e x tr a c t was washed w ith 20 ml o f 50% (w/v) potassium

154

hydroxide and d r ie d (magnesium s u l f a t e ) . The o rganic so lu tio n

was concen tra ted and f in e w hite needles formed in th e f la s k . The

product was f i l t e r e d to y ie ld 5 .8 g , 21.1 mmoles (35*0%) of 54,

0 .6 3 , m.p. 90-93°. The product showed signs of decom position

a f t e r 4 h r a t room tem pera tu re . N .m .r. d a ta (CDpl^, 60 MHz):

T4..28 (d o u b le t, H -l, J - ^ 4 .0 Hz), T5 .31 ( t r i p l e t , H-2, J 2 ^

4 .0 H z), T5 , 69-7 .00 (8-p ro to n m u lt ip le t , H-3, 4 , 5 , 6 , 6 ',-NHNH2 ) ,119T8 . 4 6 , 8 .5 7 , 8 .6 6 (3 - , 3~, and 6 -p ro ton s in g le t s , -CMe ) [ l i t .

iC(CCl^, 60 MHz): T4.28 (d o u b le t, 2 4 Hz, H - l) , T5.4 ( t r i p l e t ,

J 2 j3 0 Hz, H -2 )].

Examination of th e e th e re a l mother l iq u o rs by t . l . c .

rev ea led th e presence o f f iv e components, 0 .8 8 , 0 .7 5 , O.63

(m ajor) . 0 .43 , and 0.16 (sp o ttin g p o in t) . F u rth e r c r y s ta l l i z a t io n

did no t occur.

P h o to ly sis of 6 -0 -d im e th y lth io c a rb a m o y l- l,2 - :3 ,4 -d i-0 -

isopropylidene-c^-D -galactopyranose (4 8 ) .—A so lu tio n of 48 (4.82 g ,“ ' ' ' - — 1 " + * + *

13.9 mmoles) in methanol (150 ml) was photo lyzed f o r 113 h r . The

brown p h o to ly s is s o lu tio n was evaporated to y ie ld a brown sy rup .

The res id u e was p a r t i a l l y d isso lv e d in e th e r (50 ml) and f i l t e r e d

to g ive 553 mg of brown s o l id . The s o l id remained a t the p o in t

o f a p p lic a tio n on t . l . c . The f i l t r a t e was d eco lo rized w ith

charcoa l and evaporated to give a l ig h t yellow sy ru p . Th«

syrup was d isso lv e d in methanol (150 ml) and photo lyzed fo r an

a d d it io n a l 48 h r . The above work-up was rep ea ted to give an

a d d it io n a l 4-10 mg of re s id u e and 2.933 g of yellow syrup . An

155

n .m .r . spectrum (60 MHz) of th e crude syrup rev ea led th e absence

o f a s ig n a l f o r th e -NMe2 p ro tons o f 48 a t 16 .60 and 6 .8 2 .^

T . l . c . (so lv e n t A) rev ea led fo u r components, 0 .9 8 , 0 .93

(yellow-brown, m ajo r), 0 .7 8 , and 0 .56 (b la c k ) . T . l . c , (so lv en t B)

rev ea led n ine components, 0 .93 (very weak), 0 .86 (very weak),

0 .80 (very weak), 0 .74 (very weak), 0 .70 (m ajor, yellow -brow n),

0 .54 (weak), 0 .41 (very weak), 0 .38 (very weak), and 0.32 (m ajor,

brow n-black).

The syrup was su b je c te d to column chrom atography on s i l i c a

g e l w ith so lv e n t B as e lu e n t. F ra c tio n s (10 ml) were c o lle c te d

and m onitored by t . l . c . The f ra c t io n s c o n ta in in g th e m ajor com

ponent (R^ 0 .7 0 )were combined and evaporated to y ie ld 6 -d e o x y - l,2 :3 ,4

d l-O -iso p ro p y lid en e-a -D -g alac to p y ren o se ( 56) as a l i g h t yellow

sy ru p , 505 mg, 2 .1 inmoles (15$). The syrup was m ain tained a t -15°

and a s o l id mass o f c ry s ta l s formed o v e rn ig h t. The compound was

d i s t i l l e d a t a b a th tem pera tu re of 100-110°/0 .2 t o r r to g ive a

c o lo r le s s sy rup . The syrup c r y s ta l l i z e d upon seed in g , m.p. 33-35°,

[a ]^9 - 53 . 6 ° (c 1 .2 , ch lo ro fo rm ). Freudenberg and R a sc h ig ^ ^

re p o rte d m .p. 37°, -5 2 .4°* Cone and H ough^^ re p o rte d m.p.

30-35° a f t e r d i s t i l l a t i o n of th e p ro d u c t. The 60 MHz n .m .r .

spectrum in ace tone-d^ was id e n t ic a l to th a t d e sc rib e d by Cone T26and Hough. See T ab lesD and 11 f o r 100 MHz n .m .r . d a ta fo r

chloroform -d and ace tone-d^ s o lu t io n s ; X -ray powder d i f f r a c t io n

d a ta : 11.86 m, 9 .11 s (2 ,2 ) , 6 .57 s ( 2 ,2 ) , 6 .24 s ( 3 ,3 ) , 5.58 s

(3 ,3 ) , 5.22 s ( 1 ,1 ) , 4 .8 8 s (1 ,1 ) , 4 .56 s (1 ,1 ) .

156

The f r a c t io n s co n ta in in g th e m ajor component, 0*32

were combined and evaporated to y ie ld l ,2 :3 ,4 -d i-0 - is o p ro p y lid e n e -

a-D -galac topyranose (57 ), 1.287 g , A .94- mmoles (35.550. The l ig h t

yellow syrup was d i s t i l l e d (bath tem pera tu re 1 5 0 -l6 5 ° /0 .2 -0 .3 t o r r ) ;

[a ] 19 -5 3 .1 ° (c 6 .2 , ch lo ro fo rm ), [ l i t . [a]D -55° (ch loroform )127

and~[a]^° -59° (c 1 .4 , ch loroform )12®]. The n .m .r . spectrum fo r

a chloroform -d s o lu tio n o f 57 was comparable w ith th a t d escribed “ *****126by Cone and Hough.

C h a ra c te r iz a tio n o f l , 2 : 3 , 4 - d i -0 “iso p ro p y lid e n e -a -D-

galactopyranoso as i t s 6 -p - to lu e n e su lfo n a te (j>8).—Compound J58 was

p repared as a c r y s ta l l in e d e r iv a tiv e o f th e p h o to ly s is p ro d u c t, J 7 ,

e s s e n t ia l ly by th e method d esc rib ed by Cone and Hough.12^ Com

pound j57 (311 mg, 1 .2 mmoles) ob ta ined from the p rev ious experim ent

was d isso lv e d in p y rid in e (10 ml) and p -to lu e n e su lfo n y l ch lo rid e

(288 mg, 1 .51 mmoles) was added. The re a c t io n m ixture was

s t i r r e d f o r 2 days a t room tem peratu re and then poured onto ic e

and w ater (~100 g ) . C ry s ta l l iz a t io n d id no t occur. The aqueous

so lu t io n was decanted and 30-ml p o r tio n s o f to lu en e were tw ice

evaporated from th e syrupy re s id u e . The syrup was d isso lv ed in

e th e r (30 m l), d eco lo rized w ith a c t iv a te d carbon and evaporated

to a sy ru p . The syrup was d isso lv e d in e th an o l (2 ml) and seeded

w ith 58. C r y s ta l l iz a t io n occurred im m ediately . The c r y s ta l l i z a t io n

m ixture was r e f r ig e r a te d and j38 was ob ta ined in two c r y s ta l crops

as w hite p l a t e l e t s , y ie ld 280 mg, 0 .7 mmole (58J6), m.p. 100-101°

( l i t . m .p. 99 -1 0 0 °). The x -ra y d i f f r a c t io n p a t te r n and n .m .r .

spectrum (ch lo ro fo rm -d , 60 MHz) were id e n t ic a l w ith those

157128

p re v io u s ly re p o r te d by H orton, Nakadate, and T ronchet.

P re p a ra tio n o f 6 -d e o x y - l ,2 :5 ,6 -d i-Q -isopropylidene-c-D -125galac topy ranose ( 5 6 ) .—The procedure o f Freudenberg and Raschig

•was fo llow ed f o r th e p re p a ra tio n of an a u th e n tic sample of 56.

S u lfu r ic a c id ( l ml) was added to 6-dooxy-a-D -galactopyranose

(D -fucose, 1 .009 g , 6 .1 mmoles) (P fa n s tie h l L a b o ra to rie s , I n c . ,

Waukegan, I l l i n o i s ) In acetone (30 m l). The re a c tio n m ixture was

k ep t f o r i h r a t room tem pera tu re . The s o lu tio n was n e u tra liz e d

w ith sodium c a rb o n a te , f i l t e r e d , and evaporated to a sy ru p . T . l . c ,

o f th e syrup re v e a le d a m ajor component, 0 ,65 and 0*13 (po in t

o f a p p l ic a t io n ) . D i s t i l l a t i o n of the syrup a t 0 ,2 -0 .3 t o r r (b a th

tem pera tu re 100-116°) gave a c o lo r le s s sy ru p , y ie ld 1.15 g , A.7

mmoles (77$). The syrup was r e f r ig e r a te d (-15°) overn igh t and

w hite c ry s ta l s form ed im m ediately upon removal from r e f r ig e r a t io n ,

m .p. 35-36°. T h is compound was id e n t ic a l w ith 56 p repared by

p h o to ly s is o f AS by comparison o f n .m r. s p e c tra l d a ta and X-ray

powder d i f f r a c t i o n d a ta .

P h o to ly s is o f 3 -0 -d im ethy lth iocarbam oyl-1 ,2 :5 ,6 -d i-0 -

iso p ro p y lid o n e-a-D -g lu co fu ran o se (A 6).—A s o lu tio n of A6

(5.0A9 g , 1A.5 mmoles) in m ethanol (150 ml) was photo lyzed fo r

37 h r and th e broun p h o to ly s is s o lu t io n was t r e a te d by th e p ro

cedure used f o r p re p a ra tio n o f J 6 from £8 and the amount o f brown

re s id u e formed was 393 mg. The yellow syrup ob ta ined a f t e r d e c o lo r i-

z a tio n o f th e f i l t r a t e was re d is so lv e d in m ethanol (150 ml) and the

s o lu t io n was pho to lyzed fo r an a d d it io n a l 31 h r . P rocessing the

p roduct as b e fo re gave 262 mg o f brown re s id u o . An e th e re a l

158

s o lu t io n of th e syrup was d e co lo riz ed and evaporated to y ie ld a

yellow sy rup . The syrup was re d is so lv ed in m ethanol (150 ml) and

pho to lyzed fo r 65 h r . I s o la t io n as p re v io u s ly d esc rib ed gave

324. mg o f brown re s id u e and 2 .746 g o f yellow sy rup . An n .m .r .

spectrum (60 MHz n .m .r . spectrom eter) in d ic a te d th e absence of1s ig n a ls fo r th e -NMe? p ro to n s o f 46 a t <6.61 and 6 , 86 . The res id u e

rem ained a t th e s p o tt in g p o in t on t . l . c . (so lv e n t A). T . l . c . of

th e syrup in th e same so lv e n t system rev ea led f iv e components, Rj*

0 .9 7 , 0 .9 3 , 0.85 (m ajo r), 0 .62 (very m inor), and 0.57 (m ajor).

T . l . c . o f th e syrup (so lv en t B) as e lu e n t gave e ig h t components

R£ 0.75 (very m inor), 0.71 (very m inor), 0 .6 6 (very m inor), O.64

(very m inor), 0 .60 (m ajor), 0 ,49 (very m inor), and 0.3& (m ajor).

The syrup was su b je c te d to column chromatography on s i l i c a

g e l w ith so lv e n t A as e lu e n t. F rac tio n s were c o lle c te d every 10 ml

and m onitored by t . l . c . The f ra c t io n s co n ta in in g th e major com

ponent Rj. 0.85 were combined and evaporated to give 3 -d e o x y - l,2 :5 ,6 -

d i - 0 - is opr opylidene -c-D -r ibo-hexo'f uranos e (49) as a lig h t-y e llo w— * #***sy ru p , y ie ld 610 mg, 2 .50 mmolts (17$). The syrup was d i s t i l l e d

a t 0 .4 t o r r (b a th tem perature 115 - 125°) to g ive a c o lo r le s s syrup

“6 .3 ° (c 1 .9 , ch lo ro fo rm ). Cerny and Pacek1^ gave

-8 .6 ° (c 3 .7 , e th an o l) and HedgJoyj Overend, and Rennie‘S® gave

-5 .7 8 ° (c 4*2, e th a n o l) . The 60-MHz n .m .r . d a ta fo r carbon

te t r a c h lo r id e s o lu t io n o f 49 were In agreement w ith those rep o rte d

by Brown and J o n e s .11*? (gee T ab les30 and 11 f o r 100 MHz n .m .r ,

d a ta f o r ch loroform -d , benzene-d^, and acetone-d^ s o lu t io n s ) .

A c r y s ta l l in e d e r iv a tiv e 3 -d o o x y -l,2 -0 - iso p ro p y lid e n e -a -p -r ib p -

159

hexofuranose (51) vas p repared from 49 (44 mg, 0 .18 mmolo) by<WMp a r t i a l h y d ro ly s is accord ing to the method of Hedgley, Overend,

118and Rennie. The y ie ld o f syrupy J 1 was 32 mg, 0 .16 mmole

(89$). The syrup vas c r y s ta l l iz e d from chloroform —petroleum

e th e r to y ie ld 17 n g , 0 .08 mmole (44$) o f 51 as w hite n e ed le s ,MM118 om .p. 82-83°, [ l i t . m.p. 84 ) . The compound was id e n t ic a l by

X -ray powder d i f f r a c t i o n d a ta w ith an a u th e n tic sam ple.

The f r a c t io n s c o n ta in in g the major component (R^ 0.57)

were c o lle c te d and evaporated to g ive l ,2 :5 ,6 -d i-0 - is o p ro p y lid e n e -

a-D -g lucofuranose (50) as a sy rup , th a t c r y s ta l l i z e d : y ie ld 967 mg,

3 .71 mmoles (26$). R e c ry s ta l l iz a t io n from cyclohexane gave w hite

n e e d le s , m .p. 106° ( l i t . ^ ^ m.p. 105-109°). The n .m .r . spectrum1

o f 50 in ch lo ro fo rm -d was comparable w ith th a t p re v io u s ly rep o rted ,

and the X -ray powder d i f f r a c t io n p a t te rn d a ta were id e n t ic a l w ith

th a t of an a u th e n tic sample o f 50; X-ray powder d i f f r a c t io n d a ta :

11.62 m, 9 .73 s ( 3 ) , 8 .07 w, 6 .05 w, 5.80 vw, 5.33 s ( l ) , 4 .96 s

( 2 ,2 ) , 4 .67 w, 4 .1 6 s ( 2 ,2 ) , 3 .89 w, 3 .72 w.

The p h o to ly s is o f 46 was rep e a te d . The y ie ld of 49 wasM M «VM

2 2 .5$ and th e y ie ld o f jjO was 32$.

P h o to ly s is o f l,6 -a n h y d ro -4 - 0 - d im ethy lth iocarbam oyl-2 ,3 -

O -isopropylidene-p-D -m annopyranose ( 4 7 ) .—A s o lu t io n of 47— I .-i « i « M M MM

(1 .838 g , 6 .4 mmoles) in m ethanol was pho to lyzed fo r 69 h r and

th e brown p h o to ly s is so lu tio n was t r e a te d by th e procedure used

f o r p re p a ra tio n o f 56 from &S and th e brown re s id u e c o lle c te d was

52 mg. The d e c o lo r iz e d , e th e re a l s o lu tio n was evaporated to g ive

a yellow sy ru p . An n .m .r . spectrum o f the crude syrup in

160

chloroform -d in d ic a te d th e absence o f th e s in g le ts a t T6.62 and

T6.82 corresponding to th e -HMe protons'^ o f 47 . The syrup

c r y s ta l l i z e d spontaneously to g ive w hite n e ed le s , 806 mg. The

brown re s id u e remained a t th e p o in t of a p p lic a t io n on t . l . c .

(so lv en t A). The w hite need les were d isso lv e d in chloroform .

T . l . c . o f th e s o lu tio n (so lv e n t A) rev ea led seven components,

0.98 (m inor), 0 .96 (m inor), 0.91 (m inor), 0.88 (m inor), 0 .80 (m ajor),

0 .73 (very m inor), and 0.43 m ajor. T . l . c . of th e so lu tio n ( s o l

ven t B) showed n ine components, R£ 0 .93 (very m inor), 0.86 (m inor),

0.78 (m inor), 0 .70 (m inor), 0 ,63 (m inor), 0.57 (m ajo r), 0.46 (m inor),

0 .33 (m inor), and 0 .28 (m ajo r). The chloroform so lu tio n was evapo

ra te d to g ive w hite c ry s ta ls o f crude p ro d u c t. The product was

su b je c ted to column chromatography w ith so lv en t A as e lu e n t and

10-ml f r a c t io n s were c o lle c te d and m onitored by t . l . c . The f r a c

t io n s co n ta in in g th e major component R . 0 .80 were combined and

evaporated to y ie ld a crude c r y s ta l l in e product form ulated as 1 ,6 -

anhydro“4-deoxy-2 t3 -0 -iso n ro p y lid en e-p -D -lvxo-hexopvranose (5 9 ),

y ie ld 228 mg, 1 .2 mmoles (19^), m.p. 119-120°. R e c ry s ta ll iz a tio n

from e th an o l gave w hite n e e d le s , m.p. 120-121°, -1 6 .7 °

(c 1 .0 5 , ch lo ro fo rm ). A fte r th re e r e c r y s ta l l i z a t io n s from e thano l

th e p roduct had m .p. 125-126°, [ o ] ^ -2 1 .9 ° (c 0 .8 , ch loroform ).

N .m .r. d a ta : see TableslO and 11 f o r s o lu tio n s in chloroform -d

and ace tone-d^ ; X -ray powder d i f f r a c t io n d a ta : 7.42 s (3 ) , 6 .14 m,

5*73 s (3 ) , 5.5C s ( l ) , 5.13 m, 4 .82 s (2 ,2 ) , 4 .4 0 vvw, 4 .2 0 s

(2 ,2 ) , 3 .96 w, 3 .85 w w , 3.71 w, 3.53 v , 3 .09 w, 3.02 v .

Anal. Calcd, fo r CqH-Ô^: C, 58.49; Hf 7 .5 7 . Found:

C, 58.52; H, 7 .6 1 .

The f ra c t io n s co n ta in in g th e major component R , 0.28 were

c o lle c te d and th e so lven t was evaporated to y ie ld l ,6 -a n h y d ro -2 ,3 “

isopropylidene-fJ-D-mannopyranose (6 0 ), y ie ld 220 mg, 1 .1 mmoles

(17/6), m.p. 157-159°. R e c ry s ta l l iz a tio n from b u ty l a lco h o l gave

m.p. 160-161° ( l i t . m . p . 161-162°). The product was id e n t ic a l1*30w ith an a u th e n tic sample by n .m .r . spectrum in chloroform -d and

by X-ray powder d i f f r a c t io n p a t te r n . The p h o to ly s is o f 47 was

rep ea ted to y ie ld 26# o f J59 and 29# of 60.

P re p a ra tio n of 3 -d e o x y -3 - io d o - l,2 :5 ,6 -d i-0 - iso p ro p y lid en e -

a-D -glucofuranose (5 2 ) .—The procedure of Brown and J o n e s ^ ^ was

follow ed e s s e n t ia l ly except th a t tr ie th y la m in e was used as a base

in p lac e of N-m ethylmorpholine, and the p roduct was i s o la te d by

column chromatography in s te a d of by d i s t i l l a t i o n . To 3-deoxy-3-

h y d raz in o -l,2 :5 ,6 -d i-0 -iso p ro p y lid en e -o -D -g lu co fu ran o se (54)

(15 .0 g, 5 .5 moles) d isso lv ed in chloroform (100 m l)con ta in ing

tr ie th y la m in e (0 .77 ml, 560 mg, 5 .5 mmoles) was added iod ine

(870 mg, 11 .0 mmoles) in chloroform (200 m l). The s o lu t io n was kep t

u n t i l t . l . c . showed th a t 54 had com pletely re a c te d . The s o lu tio n

was then washed w ith aqueous sodium hydrogen s u l f i t e (io d in e co lo r

d isappeared) and d ried (magnesium s u l f a te ) . Evaporation gave

crude 52 as a l ig h t yellow sy rup , y ie ld 11 .0 g , 3 .0 mmoles (55#).

T . l . c . revea led a p r in c ip a l component, R£ 0.91 and f iv e very minor

components, Rj> 0 .8 0 , 0 .4 9 , 0 .3 3 , and 0 .2 1 . The product having R^

0 .91 was se p a ra te d by column chromatography w ith so lv e n t A as

162

e lu e n t. The so lv e n t was evaporated to g ive a l ig h t yellow syrup .

The syrup was d isso lv e d in e th e r (200 m l), d e co lo riz ed , and r e -

evaporated to g ive 52 as a c o lo r le s s sy ru p , y ie ld 8 .4 g , 2 .3«wwmmoles (4255). The syrup s o l id i f i e d spon taneously or could be

c r y s ta l l i z e d from a sm all volume o f dichlorom ethan'? to g ive c o lo r

le s s p l a t e l e t s m.p. 38-41°, -1 5 .1 ° (c 3 .0 , ch lo ro fo rm ).

The p l a t e l e t s re v e r te d to a syrup in a i r a t room tem peratu re a f t e r

a sh o r t tim e . The n .m .r . spectrum in carbon te t r a c h lo r id e was th e

same as th a t re p o r te d p r e v i o u s l y , h o w e v e r , th e rep o rte d p ro to n

assignm ents were in c o r r e c t . (See TableslO and H fo r 100 MHz

n .m .r . d a ta w ith ch loroform -d as th e s o lv e n t) .

P re p a ra tio n o f 3 ~ d e o x y -l,2 ;5 ,6 -d i-0 - iso p ro p y lid e n e -c -D-

ribo -hexofu ranose ( 4 9 ) .—A re fe re n c e sample o f 49 was prepared■ 11

from 52 accord ing to th e method o f Brown and J o n e s , C o m p o u n dMlW *

52 (1.964 g , 5 .3 mmoles) was d isso lv e d in 50 ml of e th an o l andMM

0 .5 g o f sodium a c e ta te was added to g e th e r w ith 4 g of Raney

n ic k e l No. 28 (W, R. Grace and C o., So. P i t t s b u rg , T en n .) . The

m ix ture was hydrogenated a t 20 lb in -2 u n t i l uptake ceased . The

s o lu t io n was f i l t e r e d and evapora ted to a sy ru p . The syrup was

d isso lv e d in dichlorom ethane (50 m l), washed tw ice w ith w ater,

d r ie d (magnesium s u l f a t e ) , and re -e v a p o ra te d to a sy ru p . The syrup

was d i s t i l l e d a t a b a th tem pera tu re o f 115-130°/0 .1 t o r r to give

1*173 g , 4 .8 0 mmoles (91$) o f c o lo r le s s sy ru p . T . l . c . rev ea led

th e p resence o f two coaiponents, R^ 0.87 (minor) and 0 .74 (m ajo r).

The syrup was su b je c te d to column chromatography w ith so lv e n t A

as e lu e n t and th e se p a ra tio n was m onitored by t . l . c . The f ra c t io n s

163

co n ta in in g th e component having R*. 0 .74 were c o lle c te d and evaporated20t o g ive 642 mg, 2 .6 mmoles (49^) o f 49 as a c o lo r le s s sy rup , [ a ] D

-6 .0 ° (c 5 .5 , chloroform ) [ l i t . 117 [u]£® -8 .6 ° (c 3 .7 e th an o l) and

lit.-* -1® [o]p® -5 .7 8 ° (c 4 .2 , e th a n o l) ] . The n .m .r . d a ta were in= 119 agreement w ith th o se d escrib ed p re v io u s ly . (see Tables 10 and

11 f o r n .m .r . d a ta o f ch loroform -d , benzene-d^, and ace to n e -d^

s o lu t io n s .

P re p a ra tio n o f 3~ deoxy-l,2 - 0 - iso p ro p y lid e n e -a -D -rib o -

hexofuranose (5 1 ) .—A re fe ren c e sample o f 51 was p repared as a

c r y s ta l l in e d e r iv a tiv e o f 49 p repared from 52 by an e s ta b lis h e d

ro u te . The method was a s l ig h t m o d ifica tio n o f th e one used by

Hedgley, Overend, and R ennie .11® Compound 49 (266 mg, 1 .1 mmole)

was d isso lv e d in 10 ml o f e th an o l and th e s o lu t io n was added to 400

ml o f 0 .01 N h y d ro ch lo ric a c id . The re a c tio n m ixture was kep t un

d is tu rb e d f o r 5 h r a t room tem peratu re and was then n e u tra liz e d

w ith sodium hydrogen ca rb o n a te . The aqueous s o lu tio n was evaporated

to dryness and th e re s id u e was e x tra c te d w ith th re e 30-ml p o r tio n s of

ch lo ro fo rm . The combined e x tr a c ts were evaporated to give a c o lo r le s s

sy ru p , y ie ld 0.177 g , 0 .87 mmole (79$). T . l . c . of th e syrup rev ea led

two v e ry minor components, 0 .79 and 0 .75 and a m ajor component a t

th e p o in t o f a p p lic a t io n . The syrup was c ry s ta l l iz e d from c h lo ro

form—petroleum e th e r to y ie ld 51 as w hite n e e d le s , 109 mg, 0 .53

mmole (4 8 ^ ), m.p. 82°, [ a ] jp -1 2 .6 ° (c 1 .1 , e th a n o l) , [o ]^1 -1 9 .0 °

(c 1 .6 9 , chloroform ) [ l i t . 11? m.p. 8 4 °]; X-ray powder d i f f r a c t io n

d a ta : 9 .89 vw, 8 .71 vw, 7 .51 s (2 ) , 5.42 m, 4 .8 7 s ( 1 ,1 ) , 4 .35 m,

3 .9 0 w, 3 .62 m, 3 .45 vw, 3 .20 vw. See Tables 10 a n d H fo r 100 MHz

n .m .r . d a ta in chloroform -d .

164

P h o to ly sis o f 3-deoxy-3“ io d o -1 .2 :5 .6 -d i-0 -iso p ro p y lid e n e -

g-D-e luco fu ranose ( 52) . —Compound 52 (1 .16 g , 3 .1 mmoles) was

d isso lv e d in m ethanol (150 ml) co n ta in in g d isso lv ed sodium

hydroxide (163 mg, 4*08 mmoles, 1 .3 e q u iv a le n ts ) . The so lu tio n

was pho to lyzed f o r 4 h r and evaporated to a syrup. The re s id u e

was sw irled w ith e th e r (50 ml) and yellow -w hite in so lu b le m ater

i a l (574 mg, presum ably sodium io d id e and excess sodium hydroxide)

was f i l t e r e d o f f . T . l . c . o f th e e th e r so lu tio n rev ea led a major

component (R^ 0 . 85 ) , a m inor component (Rf 0 . 55) , and a s u b s ta n t ia l

component having 0 .47 . S treak ing was observed on th e t . l . c .

p la te from th e component having 0 .4 7 to the p o in t o f a p p lic a t io n .

The e th e r s o lu tio n was evaporated to a sy rup , which was d isso lv ed

in dichlorom ethane (50 m l) . The s o lu t io n was washed w ith w ater

(50 m l), d r ie d (magnesium s u l f a t e ) , and re -ev ap o ra ted to a syrupj

y ie ld 440 mg. The p roduct was su b jo c te d to column chromatography

w ith so lv e n t A as e lu e n t. The se p a ra tio n was m onitored by t . l . c .

and th e f r a c t io n s c o n ta in in g th e component having R^ 0 .85 were

c o lle c te d and evaporated to give 49 as a c o lo r le s s sy rup , y ie ld

248 mg, 1 .0 mmoles (32^). The syrup was d i s t i l l e d a t a b a th tem

p e ra tu re o f 100- 110° / 0 .2 t o r r j [ c ]^1 - 7 . 1 ° (c 1 . 6 , chloroform )

[ l l t . 11,', [a]p® -8 .1 6 ° (c 3 .7 , e th a n o l) and lit .* * ® -5 .7 8 °

(c 4 .2 , e th a n o l) ) . The n .m .r . spectrum co inc ided w ith th a t

d e sc rib ed p re v io u s ly 11^ (see T ablesk) and 11 f o r n .m .r . d a ta of

ch loroform -d, benzene and ace tone-d^ s o lu t io n s .

The p roduct 43 (45 mg, 0 .2 mmole) was converted in to

165

c ry s ta l l in e (3 -d eo x y -l,2 -0 -iso p ro p y lid en e-a -D -rib o -h ex o fu ran o se)

by th e method a lre ad y d esc rib ed . The y ie ld o f syrup vas 26 mg,

0.13 mmole (65^). C ry s ta l l iz a tio n of th e syrup from chloroform —

petroleum e th e r gave 51 as w hite n eed les , y ie ld 18 mg, 0 .09 mmole

(£5%)f m.p. 80-81°. The compound was id e n t ic a l w ith an a u th e n tic

sample of 51 by comparison o f n .m .r . sp e c tra and X -ray powder d i f -M m

f r a c t io n p a t te r n s .

D e su lfu riz a tio n of b i s ( 1 ,2 :5 ,6 -d i-O -isop ropy lidene-a-D -

glucofuranos/1) d is u lf id e (5 5 )^ -- Compound 55 (328 mg, 0 .6 mmole)- - - - - - ■ _ - . - . - ■ ■ _ M M M M '

was d isso lv ed in ab so lu te e th an o l (40 ml) and excess Raney n ic k e l

No. 28 (W. R. Grace and Company, So. P i t ts b u rg , Tenn.) ("10 g)

was added to the so lu tio n . The re a c tio n m ixture was re flu x e d fo r

5 h r and the e th an o l so lu tio n was f i l t e r e d o f f . The Raney n ic k e l

was re flu x ed w ith two a d d itio n a l 30-ml p o rtio n s o f e thano l and the

n ic k e l was f i l t e r e d o f f . The combined e thano l f i l t r a t e was evapo

ra te d to a sy rup . T . l . c . o f the syrup revea led fo u r components,

Rj* 0,85 (m ajo r), 0.53 (very m inor), 0.36 (m inor), and a s u b s ta n t ia l

component was observed a t the a p p lic a tio n p o in t . The syrup was

su b jec ted to column chromatography w ith so lv e n t A as e lu e n t. The

chrom atographic se p a ra tio n was follow ed by t . l . c . and the f ra c tio n s

co n ta in in g th e m ajor component, Rj 0 .85 were combined and evaporated

to y ie ld 49 as a c o lo r le s s sy ru p , y ie ld 102 mg, 0 .4 mmole (33^)j

-6 .3 ° (c 1 .9 , ch lo ro fo rm ), [ l i t . 117 [ o ] ^ -8 .6 ° (c 3 .7 ,

e th an o l) and l i t . H ^ [a]^® -5 .7 8 ° (c 4 .2 , e th a n o l) ] . An n .m .r .

spectrum o f th e syrup was id e n t ic a l w ith th a t o f an a u th e n tic

166

sample o f 49 (see TableslO and 11 fo r n .m .r . d a ta fo r ch loroforra-d ,MWbenzene-d^, and a c e to n e -d ^ s o lu tio n s ) .

P a r t ia l h y d ro ly sis of the p roduct a s a lre a d y d escrib ed

fo r c h a ra c te r iz a t io n o f 49 gave 3 ~ d eo x y -l,2 -0 -iso p ro p y lid e n a -a -MMD -ribo-hexofuranose (^ l) as white need les from chloroform —

petro leum e th e r , y ie ld 41 mg, 0 .20 mraole (5 7 ^ ), m .p. 81-82°.

This p roduct was id e n t ic a l w ith an a u th e n tic sample by comparison

o f n .m .r . s p e c tra and by X-ray powder d i f f r a c t io n d a ta .

TABLE 8a

CHEMICAL SHIFT DATA FOR 1-THIO DERIVATIVES

C o m po u n d

Chemical sh ifts ( t ) and signal multiplicities*H 5 H 6

H-1 H-2 H-3 H4 H6 a H-5b H-6 a H-6 b

D

OAcintegral

Aryl p ro tons in tegral

O th e rp ro to n s

31c 5.72d 4 8 5 t 4 6 8 t 5.021 631o 573q 5 .95q786,799(61 2.74-327(6) 4.76(1) NHd8 .0 8

35 -4 .6 9 -4 .9 8 (3 ) and 6 2 6 m 572q 5 9 0 q 7 .92 ,7 .97 247,256,2.74, 7.04 (6 )5 .32 -5 4 3 (1 ) 8 0 0 ,8 .0 4 3 .3 8 ,3 4 7 (4 ) NMez

32C 5.51d 5.13 t 4 .8 0 t6 0 2 t 634m 575q 5.87q 789 ,791 , 2 .58,267, 2.72 7 .0 0 (6 )7 .99 ,801 2 32 , 3.40(4) NMe^

4 3 537d 4 4 0 - 491q 4 .40- ----- 5 .8 5 -6 .1 3 ------786, 7.89, 222-241 and4.65m 4.65m 8.03(6) 255-2.79(5)

39 4 .70 - 5 .39 5.81q 6 8 2 q e 8 9 7 8 .9 8 2 3 0 -2 5 1 and2 5 3 -2 8 0 (5 )

4 0 5.58m -4 .7 0 -5 .2 0 ------5.82q 6 .6 6 q e 7.96(9) 2 6 8 (5 ) 6 . 0 2 (2)s c h 2

41 5 2 6 d - 4 5 1 - 4 .9 8 ----- 5 .9 0 q 6 3 3 q e 784,789, 2 2 6 -2 5 2 and7.94 2 5 6 -2 8 2 (5 )

a Data from 100-MHz spec tra m easu red in CDCI3 .bS igna!sare singlets unless a range o r multiplicity ^doublet;m ^m ultip letjo ,octet; q quartet; t,triplet) is g iven .A ssig n m en ts verified by spin decoupling

^ Signal d isappears a f te r d e u te ra tio n .c Not applicable. 5

T A B L E 9

FIRST-ORDER C O U P L 1 N G - C O N S T A N T S F O R 1-THIO DERIVATIVES3

Coupling c o n s ta n ts in Hz*3

pound J4 (5 ^ 6

______________ J 1,2 J 2,3 J 3,4 J4 ,5a * J4,5b J 5a,5b J5 ,6 a J5,6b J 6 a,6 b

31 9.4 9.5 9.5 9.6 d 2.7 4.2 1 2 . 2

3 5/w *■» c c c c d 4.5 2 . 6 12.3

32 9.5 9.5 8 . 8 9.3 d 3.0 4 .5 13.0

4 3 1 0 . 0 1 0 . 2 3 3 c d c c c

3 9 c c c 5 .0 8 .9 11.9 d d d

4 0 c c c 5 .0 9.0 11.9 d d d

41-W fV______ 7.2 c c 4.2 2.3 12.3 d d d

a Data from 100M Hz sp ec tra m easu red in CDCI3- ^F or H-5a 5b 6 a 6 b(azhigh-field andb=lcw- field p ro to n s ) .c N ot m easu red due to second o r d e r e f fe c ts .^ N ot applicable.

5 6

4 9

5 9

5 2

51

TABLE 10

CHEMICAL SHIFT CATA FO R DEOXY SUGARS"

C hem ical s h i f t s ( r ) and signal m u lt ip l ic i t ie s - C om - H-3 H-4 H- 6

pound Solvent H-1__ H-2 H-3a H-3b H-4a H-4b H-5 H-6a H-6b -CMe* protons

C D C lf

(CD3)2CO

C D C lf

C < A

(CC&CO

C D C lf

(CD3)2CO

CDCIj—

C D C L

4 4 4 d 5 .68q 5.37q 5 .9 0 q 6.05 0 8.74d

4 .5 0 d 5 .68q 5 .3 6 q 5 .8 8 q 6 0 7 o 6 8 4 d a H v J ) 61'

, _ 0 0 . 7 .64 - 8 .08 - c -v rvm -s 6 .05- 8 4 9 . 8 5 8 ,4.16 d 5 2 2 1 7 g 3 r T | 8 61nn5.70-6.03 m 6 .29m 5 7 0 "6 '0 3 m 8 .64 >8 . 6 8 (S)

532d 5.601 7.82q 9 3 9 e6 .69-6 .90m |;||m5.98-6.23m gf® ’ ggfea8 2 5 - c___ 5.75- _ _ _ 8.57, 8 .65,

4 .1 9 d 5 .191 7.88q 3 5 5 ,^ 5 .7 5 - 8 3 0 1 x 1 Qi3Qm 5 .7 5 -8 .3 0 m q 71j 3 .7 3 (5 )

4 .6 6 d 6 .0 4 q 5 4 1 -5 .7 2 m 7 .70rn 7 .9 2 m 6 .2 5 m |j2 m 5 9 4 c > l o V c s ^

4 .7 8 d 6.11q 541 5 .7 0 m 7.75q d 6 .3 6 m |410 rr |6.01 q

4 .0 8 d 4 .9 9 d 5 5 8 d 6 .6 3 -6 8 9 m l o g ^ . 8 3 - 6 . 0 8 m 8 6 9 ’ 872<s)

4.14 d 5.20 1 7 .90q 8.17o 5 6 2 5 8 6 m 5 5 9 — 6 3 9 m 642q 8.47 8 8 6 s7.32 Cs)-OH

£ D ata fro m 100*MHz sp e c tra . ^ Signal multiplicity is g iv en a s s,singlet; d ,doublet; t,tr ip le t; q,quartet*, o ,o c te t; m ,m ultip le t - A ssig n m en ts v e r if ie d by spin decoupling. — Obscured by so lven t impurity ^ U n d e r a n o th e r s ig n a l

T A B L E 11F I R S T O R D E R C O U P L I N G C O N S T A N T S F O R D E O X Y S U G A R S "

Coupling c o n s ta n ts in Hz

C o m - ^23 J3,4 J4,5 J56pound S o lv en t J1<2 J~23a ^23b J3a4 J3b,4â3bJ3,4aJ34b ,4lJ4a,5 J4b,5 J5,6a%t6bJ6a,6b5 6A* — CDCIS 5.1 2.3 7 .8 c c c c 1.9 6 . 6 c

(CD^CO 5.2 2.3 7 .8 c c c c 1.9 6 . 6 c

4 9 CDCI3 4 .0 0 4.3 4.1 d 14.0 c c c d d d

CfeD6 4 .0 0 4 .3 4 .3 d 13.9 c c c d d d

(CD^CO 4 .0 0 4 .4 3.7 d d c c c d d d

5 9 CDCI3 3 .0 5 .9 c c c 5 .0e 2 .8 e 15.CP d d d 0 6.4

(CD^CO 3.0 5.9 c c c 4 .9 d 16.0 d d d 1 . 0 6.4

5 2 . CDCIS 3.6 0 3.1 c c c c d d d

51 c d c i 3 3.8 0 4 .6 4 .9 10.8 132 c c c d d 6 . 0 1 1 . 6

- D a ta from 100MHz sp e c tra .~ a = lo w field p ro to n ; b r h i g h field p ro to n ." n o t applicable ^ N o t m e a su re d d u e t o sec o n d o r d e r e ffe c ts .-O b ta in e d from spin decoupling d a ta

A P P E N D I X

171 •

3 0 0 0 2 0 0 0 1500 ' 1200 1000 900 80 0 700 cm'1m r j r i r r j r I ■ i | i i j—i

22

2 4

3 0

3 12 137 9 10 14 j rri4 5 6 8F ig . 1 . —The i . r . s p e c tra (KBr p e l l e t ) of te tra -O -a c e ty lrp -D

g lu co p y ran o sy lsu lfen y l bromide (22 ), b is ( te tra -0 -a c e ty l-p -D -g lu c o - = py ranosy l) d is u lf id e (24 ), and b is(te tra -O -ace ty l-B -D -g lu co p y ran o sy l d is u l f id e mono-oxide ($})! “ =

SSPh

OAcAcO

1 0 0 MHz CDCI,

At

1 , 1 1 1 1 1 1 1 I - i - l - l . - i - l f i l ■ I i I ■ . ■ r i r 1 1 i < r l l . i ■ i I l .. . . r l l l l < 1 i | I I 1 i _l i l l ......................... i ) I i i 1 i i 1 I I I I

1.0 2 0 3 0 4 0 5 0 6 0 70TF ig . 2 . —P a r t ia l n .m .r . spectrum of phenyl tr i-O -a ce ty l-p -2 -x y lo p y ran o sy l d is u lf id e (39).

Co

100M HzCDCL

SSPhAcO

OAc

OAc

!----- 1_______!—________ !____ 1 . ....______ !___________ I__________ 1____ I1.5 a s 35 4.5 5 5 5 5 7.5T

F ig . 3 . - - P a r t i a l n .m .r . spectrum of phenyl tr i-O -a ce ty l-a -L -a rab in o p y ran o sy l d is u lf id e (/Vl).

AcOCHx100 MHz

CDCI,

OAc

■ ■ 1 I I I 1 1 1 I I I I t I I I I I I I I I . I t I ■ I I 1 I t . I I I I I ■ I h I

1.0 2 0 3.0 4 .0 5.0 6 0 7.0 8.0

F ig . A .—N .m .r. spectrum of phenyl te tra -O -ace ty l-p -D -g a lac to p y ran o sy l d is u lf id e U 3 ).

90T

175

1 0 0 M H zCDCI,

asr1.5 2 5 7.535 6 54 5 5 5F ig . 5 .—N .m .r. spectrum o f th e crude re a c tio n product o f te tra -O -ace ty l-a -D -g lucopy ranosy l

su lfe n y l bromide (25) and b e n ze n e th io l. -

o>

(vjq oCH

H O

100M H z CDCL

ii *

j

' ■ ■ ■ 1 1 ■ ■ ■ 1 I ■ ■ ‘ - j - * ■ ‘ * ■ . i ■ < i I ■ i i i i » i ■ ■ I ■ ■ 1 . < i i i . ■ < ■ I i ■ ■ ■ i ■ ■ i i I ^ f i 1 ■ ■ i i ■ i i i i 1 i i i i i i i i i 1

4 .0 5 .0 6.0 7 .0 8 .0 90TF ig . 6 .—N .m .r. spectrum of 3 -d e o x y -l,2 : 5 ,6 - d i - 0-lsopropylidene-& -a-ribo-hexoT uranose VAVJ.

CH.

100MHzaceton e-d

CMe.

5.5 6.5 7.54.5 9.5TF ig . 7 .—N.m.r. spectrum of 6-deoxy-l,2:3,Z-di-0-isopropylidene-a-D -gal£ictopyTanose (56).

178

C H — O

!

1 0 0 MHz CDCI,

Ww»r

* A »

-----------------J

4 .0 5 .0 6 .0 7.0 BO 9.0TF ig . 8 , --N .m .r. spectrum of 1 t6-anhydro-4.-deoxy-2.3 -0 -13opropylidene-B-D-lyxo-hexopyranose (59).

-ovO

180

ORIGINAL CONTRIBUTIONS TO CHEMISTRY

The o r ig in a l c o n tr ib u tio n s t o chem istry by t h i s au th o r a re

l i s t e d below. L is t A g ives new methods of sy n th e s is developed in

con junc tion w ith t h i s re sea rch p ro je c t and L is t B g ives new com

pounds sy n th esized as p a r t of t h i s re se a rc h p r o je c t .

LIST A. NEW METHODS OF SYNTHESIS

1 . 1 -T h io -p -D -galac topyranose p e n ta a c e ta te from 2 - ( 2 ,3 ,4 ,6 -

te tra -O -a c e ty l-p -D -g a lac to p y ra n o sy l)-2 -th io p se u d o u rea

hydrobrom ide.

2 . 1-T hio-p-D -xylopyranose te t r a a c e ta te : .

a . From 2 - ( 2 ,3 ,4 -tr i-O -a c o ty l-p -D -x y lo p y ra n o sy l)-

2 -th iopseudou rea hyd roch lo ride

b . From 2 - ( 2 ,3 ,4 -- tr i-0 -ac e ty l-p -D -x y lo p y ran o sy l) -

2 -th iopseudou rea hydrobromide

3 . 1-T hio-p-D -glucopyranose p e n ta a c e ta te by a c id -c a ta ly z e d

exchange from p-D -glucopyranose p e n ta a c e ta te in

th io la c e t i c a c id .

4* N .m .r. s tu d ie s o f re a c tio n s of th e fo llow ing 1 - th io sugars

and 1 -th io g ly c o s id e s in carbon te t r a c h lo r id e w ith bromine:

a . 1-Thio-p-D -glucopyranoso p e n ta a c e ta te

b . 1-T hio-a-D -glucopyranose p e n ta a c e ta te

c . 1 -T h io -p-D -galactopyranose p e n ta a c e ta te

d . 1 -T hio-a-L -arab inopyranose te t r a a c e ta te

e . 1-Thio-p-D -xylopyranose te t r a a c e ta te

f . 1 -T hio-p-D -ribopyranose t e t r a a c e ta te

g . Benzyl 2 ,3 ,4 ,6 - te t r a -O -a c e ty l- l - th io -p -D -

glucopyranoside

h . Phenyl 2 ,3 ,4 .,6 - te tra -O -a c e ty l- l- th io -p -D -

glucopyranoside

i . 2 ,3 ,4 ,6 -T e tra -O -a c e ty l- l -S -b e n z o y l- l- th io -

p-D -glucopyranose

T etra -O -ace ty l-a -D -g lucopy ranosy l bromide by brom ination o f:

a . 1-Thio-p-D -glucopyranose p e n ta a c e ta te

b . Benzyl 2 ,3 ,4 - j6 - te tra -0 -a c e ty l-p -D -

g lucopyranoside

c . 2 ,3 ,4 ,6 -T e tra -O -a c e ty l- l-S -b e n z o y l- l-

th io -p -D -g lucopyranose

d . B is(te tra -O -ace ty l-p -D -g lu co p y ran o sy l)

d is u l f id e

e . B is (te tra -O -ace ty l-p -D -g lu co p y ran o sy l)

d is u l f id e mono-oxide

f . T e r t - b u ty l - te t r a -O -a c e ty l- l - th io -p -

E -glucopyranoside

T e tra -O -ace ty l-a -D -g a lac to p y ran o sy l bromide from 1 - th io -

p -D -galactopyranose p e n ta a c e ta te

T ri-O -ace ty l-p -L -a rab in o p y ran o sy l bromide from 1 - th io -

a-L -arab inopyranose te t r a a c e ta te

T ri-O -ace ty l-ct-D -xylopyranosyl bromide from 1 - th io -

p-D -glucopyranose te t r a a c e ta te

T ri-O -ace ty l-p -D -rib o p y ran o sy l bromide from 1 - th io -

p-D -ribopyranose t e t r a a c e ta te

T e tra -O -ace ty l-p -D -g lu co p y ran o sy lsu lfen y l bromide

from t e r t -b u ty l te tr a -O -a c e ty l- l - th io -p -D -

glucopyranoside

B is(te tra -O -ac e ty l-p -D -g lu c o p y ran o sy l) d is u l f id e by:

a . Slow brom ination of t e r t -b u ty l te tra -O -

a c e ty l- l- th io -p -D -g lu c o p y ra n o s id e

b . R eaction of d ry e thano l w ith te tra -O -

a ce ty l-p -D -g lu co p y ran o sy lsu lfen y l

bromide

c . R eaction of te tra -O -ace ty l-p -D -g lu co p y ran o -

s y ls u lfe n y l bromide w ith t e r t -b u ty l t e t r a - 0 -

a c e ty l- l- th io -p -D -g lu c o p y ra n o s id e

d . R eaction of te tra -O -ace ty l-p -D -g lu co p y ran o -

s y ls u lfe n y l bromide w ith :

(1) Acetophenone

(2) Acetone

(3) Cyclohexanone

(A) Phenol

B is(te tra -O -ace ty l-p -D -g lu co p y ran o sy l) d is u l f id e

mono-oxide by:

a . O xidation o f b is ( te tra -O -a c e ty l-p - I ) -

g lucopyranosy l) d is u lf id e w ith

m -chloroperoxybenzoic a c id

183

b. Reaction of tetra-O-acetyl-p-D-glucopyrano-sylaulfenyl bromide with water

c . Reaction of tetra-O-acetyl-p-D-glucopyrano-s y ls u lfe n y l bromide w ith 95% e th an o l

13. £-(D im ethylam ino)phenyl te t r a -O -a c e ty l- l - th io -p -D -

glucopyranoside from te tra -O -a c e ty l-p -D -g lu c o -

p y ran o sy lsu lfen y l bromide and N ,N -dim ethylaniline

14- A ro u te t o deoxy sugars by p h o to ly s is o f d im e th y lth io -

carbam ates:

a . 6-D eoxy-lJ2 :3 j4 --d i-0 -iso p ro p y lid e n e -a -p -g a la c to -

pyranose from p h o to ly s is o f 6 -0 -d im e th y lth io -

ca rb am o y l-l,2 :3 ,4 -d i-O -iso p ro p y lid en e -a -D -

galactopyranose

b . l,6 -A nhydro-4-deoxy-2 ,3“0-isopropylidenG-{3-D-

ly x o -hexopvranose from p h o to ly s is o f 1 ,6 -anhydro-

A -Q -d im ethy lth iocarbam oyl-2 ,3 -0 -is opropylidene-

p-D-mannopyranose

c . 3 * 'D 3 o x y -l,2 :5 ,6 -d i-0 -iso p ro p y lid en e -a -p -rib p -

hexofuranose. from p h o to ly s is o f:

(1) 3“0-D im ethy lth iocarbam oy l-1 ,2 :5 ,6 -

d i-O -isop ropy lidene-a -D -g luco fu ranosc

(2) 3 -D eo x y -3 -io d o -l,2 :5 J6 -d i-0 -iso p ro p y lid e n e -

o-D -glucofuranose

(3) By re d u c tio n o f b i s ( l ,2 :5 ,6 - d i - 0 - i s o p r o p y l i -

dene-a-D -g lucofuranosy l) d is u l f id e with

Raney n ic k e l

LIST B. NEW CHEMICAL COMPOUNDS1 . B is (te tra -O -ace ty l-p -D -g lu co p y ran o sy l) d is u lf id e

mono-oxide

2 . T etra-O -acety l-p-D -glucopyranosylsu lfenam idobenzene

3 . £-(D im ethylan)ino)phenyl te tra -O -a c e ty l-p -D -

g lucopyranosyl d is u l f id e

4 . Phenyl tri-O -a ce ty l-p -D -x y lo p y ra n o sy l d is u l f id e

5. Benzyl tr i- tt-a c e ty l-p -D -x y lo p y ra n o sy l d is u lf id e

6 . Phenyl te tra -O -a c e ty l-p -D -g a lac to p y ra n o sy l d is u lf id e

7* Phenyl tr i-O -a e e ty l-a -L -a ra b in o p y ra n o sy l d is u l f id e

8 . l 16-A nhydro-4-deoxy-2.3-Q -isopropylidene-P-D -lyxo-

hexopyranose

SYNTHESIS WITH THIO SUGARS - OhioLINK ETD

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