Chuyen de Boi Duong Hoc Sinh Gioi Hoa 12

7/22/2019 Chuyen de Boi Duong Hoc Sinh Gioi Hoa 12

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Bin son v hng dn: PGS.TS Trn HinCHUYN BI DNG HC SINH GII-----------------------------------------------------------

CHNG I: AMIN V MUI IAZONIBi: AMIN

I.KHI NIM1.nh ngha

Amin l dn xut th H ca NH3, bng cc gc hirocacbon bo hay thm.Amin loi bo: gc hirocacbon l gc ankyl hay xicloankyl

CH3-CH2CH2-NH2Amin thm, gc hyrocacbon l nhn thm:

NH2

2.Bc amin:Amin bc 1, c nhm chc amin -NH2 nh vi 1 gc hirocacbonAmin bc 2, c nhm chc amin NH nh vi hai gc hirocacbonAmin bc 3, N nh vi 3 gc hirocacbon

RNH2 (CH3)2CNH2 R2NH CH3CH2NHCH3 R3N (CH3)3Namin bc nht amin bc hai amin bc baII.DANH PHPAmin thng c gi theo tn thng thng hn l IUPAC

Tn gc hirocacbon+amin(vit lin 1 ch)

X-amino + tn hirocacbon

Tn thng thng Tn IUPACCH3NH2(CH3)2NH

(CH2CH2CH2)3NCH3CH

2CH-NH

2

CH3

CH3CH

2CH - N - CH

2CH

3

CH3

CH3

NH2

N(CH3)2

NH2

CH3

metylaminimetylamin

tri-n-propylaminsec-butylamin

metyletyl-sec-butylamin

phenylamin,anilin

imetylphenylaminimetylanilin

p-toluiin

aminometanN-metylaminometan

N,N-ipropylaminopropanAmino-2-butan

N, N-etylmetylamino-2-butan

aminobenzen(benzenamin)

N, N-imetylbenzenaminN, N-imetylanilin

p-aminotoluen


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NHR NR2

CH3

NH2

CH(CH3)2

CH3

NO2

CH(CH3)2

CH3

NH2

NH2

CH3

NO2

NO2

Bin son v hng dn: PGS.TS Trn Hin

III.PHNG PHP TNG HP1. Ankyl ha trc tip amoniac hay amin

NH3 tc dng vi RX to thnh mui:CH3CH2-Br + NH3 CH3CH2NH3+Br- NaOH CH3CH2NH22.Phn ng kh

a, Kh hp cht nitroNhm nitro b kh thnh amin bc nht. Phn ng ch yu dng iu ch amin thm. Tc nhn kh c thl hiro ha xc tc hay tc nhn kh ha hc trong dung dch.

[H]p, to

FeC2H5OH, HCl, to

b,Kh hp cht nitrinNitrin b kh bng hiro trn xc tc hoc bng LiAlH4 trong dung dch to thnh amin bc nht:

H2/NiR-CN R-CH2-NH2

hay LiAlH4IV.CU TRC

Amin l sn phm th ca NH3, nn ni chung c cu trc ging cu trc ca NH3:NH3 R-NH2 R-NH-R R-N-R

|R

V.TNH CHT HA HC1. Tnh baz

Amin l baz Lewis do amin c cp electron n khng lin kt N tng t nh ancol, ete. Khi xt mtamin c tnh baz, cn so snh tnh n nh ca amin so vi mui amoni. Nu ion amoni n nh hnamin th amin c tnh baz. Khi so snh tnh baz ca amin bo, cn ch hai nhn t: nhn t phn ccv nhn t solvat ha.

Nu xt theo nhn t phn cc, khi tng gc R s lm tng mt electron N, va lm tng kh nngkt hp proton, va lm tng tnh n nh ca ion amoni. Do tnh baz gim theo th t:R3N > R2NH > RNH2

Nu xt theo nhn t solvat ha ca ion amoni, s lng proton ion amoni cng nhiu th kh nngsolvat ha ca ion cng ln, do , tnh baz thay i theo th t:

RNH3+ > R2NH+2 > R3NH+Tng hp c hai nhn t trn, s thay i tnh baz ca cc amin c bc khc nhau nh sau:RNH2 < R2NH > R3NTnh baz ca cc amin thm bo cng thay i theo th t nh trn:

< >NH2


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)(+

Bin son v hng dn: PGS.TS Trn HinArN

)(+

NX(-) (t ArNH2). C ch phn ng ca amin bc mt tng t trng hp amin bc hai ch lc

u cng to ra hp cht nitroso, sau phn ng tip nh sau:

R - N = NOH2 NR- NH - N = OH

R- NH = NOH

+ H-+

R - N = NOHH

+ +R - N

ng ch l mui iazoni dy bo RN N khng bn nn chuyn ho ngay thnh ancol gii phong kh nit.

Trong khi y, mui iazoni dy thm li bn nhit thp v ch phn hu thnh phenol ng thi giiphng N2 khi un nng. Th d:

C2H

5- NH

2

NaNO2

C2H

5- N NCl

OH2

N2

C2H

5OH

HCl, 00C

+ -+ + HCl

C6H

5- NH

2

NaNO2

OH2

N2

C6H

5OHC

6H

5- N NCl

HCl, 00C

+ -+ + HCl

un

Mui iazoni thm ArN2(+)X(-) c dng rng ri trong tng hp hu c.3.4. Phn ng th nhn thm:

Cc nhm -NH2, -NHR v - NR2 (R = ankyl) u hot ho nhn thm v nh hng ortho - para.a, Halogen hoNc brom d dng phn ng vi anilin cho 2, 4, 6 - tribromoannilin (kt ta trng), vi p - toluidin p -

CH3C6H4NH2 cho 2,6 - ibrom - 4 - metylanilin.Brom lng tc dng vo v tr para ca N - axetylanilin (hay axetanilit) C6H5NH - COCH3; thu

phn sn phm sinh ra s c p - bromanilin.Iot trong hn hp vi NaHCO3 ( trung ho HI sinh ra trong phn ng) tc dng vi anilin cho ta p -

Iotanilin.b, Nitro ho

Khng th trc tip nitro ho anilin bng HNO 3, v khi y amin b proton ho tr thnh mui amoni; nhm -

3

)(

HN

+

sinh ra s phn hot ho rt mnh v nh hng th vo v tr meta, mun mononitro ho anilin phibo v nhm - NH2 ri mi nitro ho, sau gii phng - NH2.

NH2 NHCOCH

3NHCOCH

3

NO2

NH2

NO2

(CH3CO)

2O HNO

3, H

2SO

4H

3O+

OH-

1)

2)

Nu muna nhm nitr vo v tr ortho phi kho v tr para ri mi nitro ho:


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Bin son v hng dn: PGS.TS Trn HinNH

2 NHCOCH3

NHCOCH3

SO3H

(CH3CO)

2O H

2SO

4HNO

3, H

2SO

4

NHCOCH3

SO3H

HNO3, H

2SO

4

NHCOCH3

SO3H

NO2

H2SO

4

OH2

NHCOCH3

NO2

Bi: MUI IAZONI

I.CU TRC CA CATION IAZONIIon iazoni c nhm N2 hay NN mang in tch dng phn b trn c hai nit nhng tp trung Nnh vi phn t benzen nhiu hn:

N N N N

(Ar-N2)hay

++ +

trong h lin hp, mt lin kt lin hp c vi h ca nhn benzen cn mt lin kt nm thng gcvi mt phng ny

II.TNH CHT HA HCMui iazoni thm ArN2(+)X(-) c th ng vai tr l cht phn ng trong cc phn ng thay th nhm -

N2(+), mt khc c th l tc nhn electrophin tham gia phn ng th electrophin nhn thm, l phn ngghp.1. Phn ng th nhm -N2(+)

1.1. Th -N2(+)bng -OH v bng -I

Ar - N N-N

2

Ar - Y+

Ar+Y

-

Khi un nng dung dch ArN2(+), H2SO4(-) trong nc s sinh ra ArOH theo c ch nu trn (H2SO4(-) c tnhnucleophin km H2O). Phn ng ny c dng tng hp phenol t amin thm. Th d:

m - NO2C

6H

4NH

2

NaNO2, H2SO4, H2Om - NO

2C

6H

4N

2HSO

4OH2 m - NO

2C

6H

4OH N2

+ -

t0+

Khc vi H2SO4(-) c tnh nucleophin km nc, anion I(-) c tnh nucleophin cao hn nc nhiu, nn d tcdng vi mui iazoni sinh ra ArI. Th d:

C6H

5NH

2

NaNO2, HCl

C6H

5N

2Cl

KIC

6H

5I

0 - 50C 250C

+ -


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Bin son v hng dn: PGS.TS Trn Hin1.2.Th -N2(+) bng - Cl, -Br v -CN (phn ng Sandmeyer)

Nh tng git huyn ph ca Cu2X2 (X = Cl, Br hoc CN) vo dung dch ArN2(+)X(-) lnh s xy ra phnng th -N2(+) bng -X. Th d:

C6H

5NH

2

NaNO2, HCl

C6H

5N

2Cl

KIC

6H

5I

0 - 50C 250C

+ -

o-ClC6H

4NH

2

NaNO2, HBro-ClC

6H

4N

2Br

Cu2Cl2o-ClC

6H

4Br

0 - 50C

+-

p-CH

3C

6H

4NH

2

NaNO2, HCl

p-CH3C

6H

4N

2Cl

Cu(CN)2

p-CH3C

6H

4CN

0 - 50C

+ --

1.3. Th -N2(+) bg -F v -NO2 Sau khi iu ch mui areniazoni tetrafluoroborat ArN2(+) BF4(-) em nhit phn s c ArF hoc cho tcdng vi NaNO2/Cu s c ArNO2. Th d:

p-NO2C6H4NH2

NaNO2

HBF4 p-NO2C6H4N2BF4

-N2, -BF3

NaNO2/Cu

p-NO2C

6H

4F

p-(NO2)2C

6H

4

+ -

to

1.4. Th -N2(+) bng -H. Phn ng kh:Dng axit hipophotphor(H3PO2) hoc etanol c th kh c mui iazoni ArN2(+) thnh ArH:

ArNH2

NaNO2, H

ArN2

H3PO2

C2H

5OH

+

0 - 50C hocArH

Nh phn ng ny ngi ta c th loi b nhm amino trong vng thm v do tng hp c nhng dnxut th khng th iu ch bng phn ng th trc tip. Th d t toluen tng hp m - bromotoluen:


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CH3

NHCOCH3

Br

CH3

CH3

NH2

Br

CH3

N2(+)Cl-

Br

CH3

Br

CH3

NO2

CH3

NH2

CH3

NHCOCH3

HNO3 Sn, HCl (CH3CO)2O Br2

H3PO

2

-H3PO

3

NaNO2

OH2

xtHCl

2. Phn ng ghp:

Ion arenddiazoni ArN2(+) l nhng tc nhn electrophin khng mnh, thng ch tc dng vi nhng chtthm giu mt electron nh amin, phenol,...theo c ch electronphinin:

R - N N YH YR-N=NS+

+E 2

Cu t iazo Cu t azo Hp cht azo2.1.Phenol v dn xut

Nu cu t azo l phenol, phn ng ghp xy ra v tr para v pH ti u l 9 - 10 chuyn -OHthnh -O(-) c hiu ng +C mnh hn. pH cao hn ArN )(+

N s chuyn thnh ArN = NOH v Ar - N = N-O(-)

khng cn tnh electrophin. Th d:

C6H

5- N N O C6H5-N=N

S

O+

+E

2(-) (-)

2.2.Amin thmNu cu t azo l amin thm bc 3 nh C6H5 - NR2pH thun li l 5-9, phn ng cng xy ra v tr

para. Th d:

C6H

4-N N N(CH

3)2 N(CH3)2C6H5-N=N

+

+

Phnng mui iazoni vi amin thm bc mt xy ra nguyn t nit. Th d:

C6H

5- N N C

6

H5

-N=N - NH - C6

H5

H2N - C

6H

5

+

+

i vi amin thm bc hai nh C6H5NHCH3 phn ng xy ra c nit ln v tr para ca vng thm.Th d:


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C6H

5- N N NHCH

3

C6H

5- N=N NHCH

3

C6H

5- N=N - N(CH

3)2

+

+


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CHNG II: AMINOAXIT - PROTIT

Bi: AMINOAXITI. NH NGHA-CU TRC - DANH PHP

1.nh ngha: Aminoaxit l cc HCHC tp chc, phn t c cha ng thi

nhm chc -NH2

(amino) v -COOH (-cacboxyl)2.Cng thc tng qut: CT chung: (NH2)x R (COOH)y

x = y hoc x > y hoc y > x Khi x=1, y= 1, R: no, mch h th CT l

NH2 - CnH2n - COOHVD: C3H7O2N ng phn aa?(2 p) 3.Cu trc: a s cc aa thin nhin l cc , dy L

trng thi rn tn ti ion lng cc, trong dung dch tn ti dng cn bngV d 1: Cu hnh R/S v D/L ca hu ht cc amino axit l g ? (b) Vit cu hnh tuyt i ca (i) L- cystein v (ii)

L-serin.

(a) S v L

(b) (i)

COO

CH2SH

HH3N

(ii)

COO

CH2OH

HH3N

V d: (a) Vit tt c cc ng phn lp th ca threonin (dng cng thc Fischer).(b) Xc nh L-threonin v cho bit danh php R/S ca n.

(a)COO

-

CH3

H

OH

H3N+

H

COO-

CH3

+NH3

H

H

HO

COO-

CH3

H

H

H3N+

HO

COO-

CH3

+NH3

OH

H

H

racemat-1 (threo) racemat-2 (erythro)

(b) Cc cu hnh tng ng vi racemat-1 l L- v D-threonin, vi racemat-2 l L- v D-allothreonin, L- cxc nh theo cu hnh ca C . Nu c mt C bt i trong nhm R, cu hnh ca n khng lin quan n khiu D,L hay R,S ca amino axit. L-threonin l (2S,3R). ng phn lp th dia - (2S,3S)-threonin- c gi l

L-allothreonin4.Danh php:

a,Tn thng:Axit +K hiu v tr (-NH2) [(,,,...)]+ amino + tn thng thng ca axit tng ng

b,Tn quc t:Axit+v tr nhm -NH2 +amino+tn quc t ca axit HC.


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5.Tnh axit , baz ca aa

Tn K hiu Cng thc

Monoaminomonocacboxylic

Glixin Gly H3N+CH2COO-Alanin Ala H3N+CH(CH3)COO-

Valin* Val H3N+CH(i-Pr)COO-

Leuxin* Leu H3N+CH(i-Bu)COO-

Isoleuxin* ILeu H3N+CH(s-Bu)COO-

Serin Ser H3N+CH(CH2OH)COO-

Threonin* Thr H3N+CH(CHOHCH3)COO-

Monoaminodicacboxylic v dn xut amit

Axit aspatic Asp HOOC-CH2-CH(+NH3)COO-

Asparagin Asp(NH2) H2NOC-CH2-CH(+NH3)COO-Axit glutamic Glu HOOC-(CH2)2-CH(+NH3)COO-

Glutamin Glu(NH2) H2NOC-(CH2)2-CH(+NH3)COO-

Diaminomonocacboxylic

Lysin* Lys H3N+-(CH2)4-CH(NH2)COO-

Hydroxylizin Hylys H3N+-CH2-CHOH-CH2-CH2-CH(NH2)COO-

Arginin* Arg H2N+=C(NH2)-NH-(CH2)3-CH(NH2)COO-

Aminoaxit cha lu hunh

Systein CySH H3N+CH(CH2SH)COO-

Cystin CySSCy-

OOC-CH(+

NH3)CH2S-SCH2CH(+

NH3)COO-

Methionin* Met CH3SCH2CH2CH(+NH3)COO-

Aminoaxit thm

Phenylalanin* Phe PhCH2CH(+NH3)COO-

Tyrosin Tyr p-C6H4CH2CH(+NH3)COO-

Aminoaxit d vng

Histidin* His

N

HN

CH2 CH+NH3

COO-

Prolin ProN

H H

H

COO-


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Hydroxyprolin Hypro

NH H

H

COO-

H

HO

Tryptophan*

TryNH

CH2 CH

+NH3

COO-

II. Tnh cht vt l:Cht rn, khng mu, a s tan tt, c nhit nc tng i cao.

III. Tnh cht ho hc:1. Tnh cht axit-baz: im ng inTnh lng tnh

baztnh

axittnh

OH- + H3N+CHRCOOH D H3N+CHRCOO- +H2O

D H2NCHRCOO- + H3O+

cation A ion lng tnh B anion C(+1) (0) (-1)

Gi tr pH m ti phn t aminoaxit tn ti dng ion lng cc (I) cn bng v in tch v khng dichuyn v mt in cc no c c gi l im ng in v k hiu l pH1.

Gi tr v im ng in ca cc aminoaxit thin nhin c gii thiu bng 17.1.im ng in ca cc axit monoaminomonocacboxylic tnh c theo biu thc:

2

21

1

aa pKpKpH

+

=

Gi tr pKa1 ng vi nhm -COOH, pKa2 ng vi nhm .3HN+

V d i vi glyxin, pKa1 = 9,6 tnh c

pH1 = (2,34 + 9,6) : 2 = 5,97.Cc aminoaxit c gi tr pH1 khc nhau nn mt gi tr pH xc nh cc aminoaxit s dch chuyn v catot

hoc anot vi nhng vn tc khc nhau. Da vo c tnh ny ngi ta xy dng phng php in di phn tch aminoaxit t hn hp ca chng.2. Tnh cht ca nhm cacboxyl:

a, Phn ng este ho:Tng t axit cacboxylic, aminoaxit phn ng vi ancol c axit v c xc tc cho este ( dnh mui). V

d:

H3N - CH(R) - COO C

2H

5OH H

3N - CH(R) - COOC

2H

5

OH2Cl+

bo ha kh HCl+

+ - +

Ra sn phm bng dung dch NH3 s thu c este:H2N- CH(R) - COOC2H5.

b, Phn ng ecacbolxyl ho:Phn ng tch CO2 t nhm cacboxyl xy ra trong c th nh enzim ecacboxyllaza:

H2N - CH(R) - COOH zadecaboxyla R - CH2 - NH2 + CO2


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Bin son v hng dn: PGS.TS Trn Hin3. Tnh cht ca nhm amino:

a, Phn ng vi axit nitr HNO2 Tng t cc amin bc mt, aminoaxit phnu ng vi axit nitr gii phng ra N2 v to thnh hiroxiaxxit:

OHNCOOHRCHHOHONOOCORCHNH 223 )()( ++++

Da vo th tch N2 thot ra c th tnh c lng aminoaxit trong dung dch. b, Phn ng eamino ho (tch nhm amino)

Phn ng xy ra trong c th nh enzim, aminoaxit chuyn thnh xetoaxit v NH3. V d:CH3 - CH(NH2) - COOH [ ] enzimO , CH3 - C - COOH + NH3

OAlamin Axitpiruvic

c, Phn ng ankyl ho hoc aryl hoNhm amino ca aminoaxit c ankyl ho hoc aryl ho bng dn xut halogen to ra dn xut N-ankyl

hoc N - aryl tng ng. V d :

CH3I H3N - CH2 - COO N

H

H

CH3 CH2-COO+ + HI

-+ + -

FO2N

NO2

H3N - CH

2- COO O2N

NO2

NH-CH2-COOH

-++ + HF

N-(2,4-dinitrophenyl) glyxin d, Phnng axyl ho:

Nhm amino ca phn t aminoaxit c axyl ho dng bi halogenua axit trong mi trng kim.Vd:

O

C6H

5- C - Cl H

3N - CH(R) - COO

OH /H2O

HO

C6H

5- C - NH(R) - COOH + HCl-

+

+

1) -

2)+

Cng c th axyl ha bng anhirit axetic:Cng c th axyl ha bng anhirit axetic:

O

(CH3- CO)

2O H

3N - CH(R) - COO

O

CH3

- C - NH(R) - COOH + CH3COOH+

-+ t0

e, Phn ng ngng t vi anehit fomic (Phn ng sorenxen)

Aminoaxit phn ng d dng vi anehit fomic to thnh dn xut cha nhm metylenamino: OHCOOHRCHNCHOHCHOCORCHNH 223 )()( +==+

+

Do nhm amino b kho nn c th chun nhm cacboxyl bng kim. y l phn ng quantrng dng nh lng aminoaxit v nh gi mc thu phn protein.4. Tnh cht ca c phn t: a, Tc dng ca nhit


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Bin son v hng dn: PGS.TS Trn HinCc-aminoaxit (hoc este cachng) khi un nng to thnh iamitvng 6 cnh c gi l

ixetopiperazin, do hai phn t aminoaxit b tch hai phn t nc (hoc hai phn t ancol). V d:

O

CH2

NH

NH

CH2

O

OH2

NH3

CH2

O

C

OH

3N-CH

2

C = OO Dixetpiperazin

+t0

+

+ -

-

+

NH2

R - C OC2H

5C

O

H2N-CH - R

C = OC2H5O

O

R-CH

NH

NH

CH-R

O

C2H

5OH

++

+t0

Diankyldixetopiperazin

Tng t cc amit, cc i xetopiperazin b phn hu trong mi trng axit hoc baz, trc ht m vng

tao thnh hai phn t aminoaxit:

O

CH2

NH

NH

CH2

O

H2O, H

O

H3N CH

2- C - NH - CH

2- COOH

H2O, H

H3N - CH

2- COO

++

(nhm peptit) Dipeptit

+-+

2

Khi un nng, ipeptit li khp vng to thnh ixetopiperazin.Cc -aminoaxit b tch NH3 bi nhit to thnh axit, -khng no:

H

3N - CH

2- CH

2- COO CH2=CH-COOH +NH3

-+ t0

Cc va, -aminoaxit di tc dng cuat nhit b tch nc to thnh amit vng, thng gi llactam:

CH2

- CH2

- CH2

C = OONH3C=O

C

H2

C

H2

CH2

NH

OH2-+

to

+

Butirolactam

b, Phn ng to hp cht phcCc -aminoaxit phn ng c vi mt s ion kim loi nng cho hp cht phc kh tan, thng c mu

c trng. V d hp cht phc ca glyxin vi Cu2+:


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OH2Cu

OC1

CH2

NH2

O

O C1

CH2

NH2

O

CH2

- COO

NH3

Cu(OH)2 +

-

+

2 +

Kt ta mu xanh

2

5. Phn ng mu ca aminoaxit: a, Phn ng vi ninhirin

Cc -aminoaxit phn ng vi ninhirin (cn gi l trixeto hirinen hirat) cho sn phm mu tm xanhtan trong nc (ring prolin cho sn phm mu vng):

OH

OH

O

O

R - CH - COOH

NH2

OH

H

O

O

NH3 CO2 RCH=O

O

O

N

O

O

NH3

+ + + +

tm xanh

+ Ninhidrin

+

Phn ng rt nhy, c th pht hin n microgam -aminoaxit, v vy phn ng ny c dng phntch nh tnh v inh lng cc -aminoaxit. nh lng -aminoaxit c th dng phng php so muo cng mu dung dch phn ng, hoc dng phng php o th tch CO2. b, Phn ng xangtoproteic

Cc aminoaxit c gc hirocacbon thm (Phe, Tyr, Trp...) phn ng vi HNO 3 c nng cho sn phmmu vng.

c, Phn ng vi thuc th MilonCc aminoaxit c gc phenol (Tyr...) phn ng vi thuc th Milon (hn hp Hg(NO3)2 v HNO3 c) khiun nng cho sn phm mu . d, Phn ng Pauli

Phn ng Pauli c trng cho tryptophan. Tryptophan phn ng vi axit iazobenzensunfonic trong dungdch kim cho sn phm c mu anh o. e, Phn ng Aamkevic v Hopkin

Phn ng c trng cho aminoaxit cha vng inol nh tryptophan. Tryptophan phn ng vi axit gloxilic(O=CH-COOH) c mt H2SO4 c cho sn phm c mu tm. g, Phn ng Sacaguchi

Phn ng c cho arginin. Arginin phn ng vi hn hp natri -naphtolat v natri hipobromat cho sn

phm mu .IV-IU CH AMINOAXIT1.Thu phn protein

Thu phn protein nh xc tc axit, hoc kim hay enzim thu c hn hp cc L-aminoaxit:


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H2N-CH

R

CO NH-CH CO -

R'

HN-CH

R"

CO - ...H

2O/H

H2N-CH

R

COOH H2N-CH

R'

CO HN-CH

R"

COOH+ + ....

Nh cc phng php thch hp (sc, k, in li...) c th tch ring r tng aminoaxit.2.Amin ho axit -halogencacboxylic (phong php Peckin)

Cho axit -halogencacbylic tc dng vi dung dch amoniac c nhit phng thu c -aminoaxit.

H2N-CH

X

COOH NH3

H2N-CH

NH3

COO - NH4Br+ 2

++

3.Ankyl ho cc este ca axit aminomalonic N-thEste ca axit aminomolonic N-th (III) c iu ch t ietyl monobrommalonat (I) v kali phtalimiat

(II):

O

O

N-

BrCH(COOC2H

5)2

O

O

N CH(COOC2H5)2K+

+-KBr

DietylN-phtalimitmalonat

(I)

(II)(III)

ietylN-phtalimit malonat (III) c ankyl ho bi ankyl halogenua hoc hp cht caconyl , -khng no, sau un nng sn phm ankyl ho trong mi trng axit xy ra qua qu trnh thu phn este v ecacboxyl ho

thu c -aminoaxit:

O

O

N CH(COOC2H5)2

O

O

N CR(COOC2H5)2

H3O+

-CO2

R-CH - COO

NH3

COOH

COOH

C2H

5OH

(III)

1)Bazo

RX2)(III)

-

+ ++

Phng php ny c dng iu ch nhiu a-aminoaxit, v d methionin, axit glutanic...:


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O

O

N CH(COOC2H5)2

C2H

5ONa

C2H

5ONa

CH3SCH

2CH

2Cl

CH2=CH-COOC

2H

5

H2O/H+

H2O/H+

CH3SCH

2CH

2-CH - COO

NH3

HOOCCH2CH

2-CH - COO

NH3

(III)

1)

2)

2)

1)

to

to

-

+

+

-

Me thionin

Axit glutamic 4.Tng hp Streck (Strecker)

Cc -aminoaxit cng c tng hp bng cch thu phn cc -aminnonitrin theo s phn ng:

RCH=O +NH3

+ HCN R-CH-N N

NH2

H2O/H R-CH

NH3

COO -+ +

+

5. iu ch v -aminoaxitAxit - aminocaproic v axit - aminoenantoic (u khng c trong thin nhin) l nguyn liu quan

trng sn xut t capron v t enang.

Axit - aminocaproic c iu ch t oxim ca xiclohexanon. Khi un nng oxim ny vi H 2SO4 c thuc caprolactam, sau thu phn thnh axit -aminocaproic:

O H2N-OH

OH2

N-OHH

2SO

4

C

H2

C

H2

C=OCH

2NH

CH

2

CH

2

H2O/H H

2N-(CH

2)5-COOH

Oxim ca xiclohexanon

c

+

Axit -aminoenantoicc iu ch t etilen v cacbon tetraclorua nh phn ng telome ho to thnh 1,1, 1, 7 - tetraclohepan, sau thu phn v amin ho:

CH2=CH

2

CCl4 ClCH

2-(CH

2)5-CCl

3

H2O/H

2SO

4

ClCH2-(CH

2)5-COOH

NH3 NH

2CH

2-(CH

2)5-COOH

3

Bi: PEPTITI - Trng thi thin nhin:

Mt s cht peptit c trong c th ngi. V d nh trong m c c cacnozin v anserin (u l ipeptit), gan v no c glutation (tripeptit). Glutation cn c trong mm la m v mt s loi nm. Mt s peptit lhormon trong c th sinh vt nh insulin, oxytoxin...II - Cu trc v danh php: 1. Cu trc

Peptit thin nhin l hp cht polime ca cc oaxitamin , gm t 2 n khong 50 n voaxitamin kt hp vi nhau nh cc lin kt peptit.

Lin kt peptit


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... - HN-CH

R

CO NH -CH

R1

CO - ...

Nhm peptitTu thuc vo s n v (2, 3, 4, ..., n) aminoaxit trong phn t ngi ta phn chia thnh ipeptit, tripeptit,

tetrapeptit...polipeptit. Theo quy c mt peptit c phn t khi trn 10000 c gi l polipeptit; nhngpeptit c phn t khi thp hn c gi l oligopeptit.

Trong phn t peptit, u mch cha n v aminoaxit cn nhm -NH 2 ( +NH3) c gi l u N, cnu mch kia cha n v aminoaxit cn nhm -COOH (hay COO --) c gi l ui C. Theo quy c, umch c nhm -NH2 c vit pha bn tri, cn u c nhm -COOH c vit pha bn phi:

-CH

R

CONHH2N-CH

R

CO NH - CH

R

COOH

Aminoaxit u N Aminoaxit u C

Nhm peptit -CO -NH- c cu trc phng, nguyn t H ca nhm -NH- nm v tr anti i nguyn t Oca nhm cacbonyl. Lin kt peptit C-N mang mt phn c im ca lin kt i C=NDo vy lin kt peptit kh quay t do xung quanh trc C-N, trong khi kh nng quay t do ca cc lin

kt n gia C vi nhm peptit l rt ln. l nguyn nhn dn n cu trc xon ca mch polipeptit(xem bi protein).

Tng t aminoxit, phn t peptit cng tn ti dng ion lng cc, peptit l hp cht lng tnh.*Tnh axit v baz

V d: C mt hn hp protit gm pepsin (pHI = 1,1), hemoglobin (pHI = 6,8) v prolamin (pHI = 12,0).Khi tin hnh in di dung dch protit nu trn pH = 7,0 thi c ba vt cht (xem hnh)

Xut ph t

Cc (+) Cc (-)

A B C

Cho bit mi vt cht c trng cho protit no ? Gii thch.

Bi gii :Vt A l pepsin, vt B l hemoglobin v vt C l prolamin.Gii thch : Pepsin l protit c tnh axit mnh (pH I = 1,1) nn tn ti dng anion khi pH =7, di tcdng ca in trng s chuyn v cc dng (anot). Hemoglobin (pH I = 6,8) hu nh tn ti lng ccvi in tch bng khng khi pH = 7, do gn nh khng chuyn dch. Prolamin l protit c tnh bazmnh (pHI = 12,0) nn tn ti dng cation khi pH =7, di tc dng ca in trng s chuyn v ccm (catot).

2. Danh phpTn ca cc peptit c gi theo quy tc sau:- Ghp tn cc aminoaxit to nn phnt peptit theo trt t sp xp ca chng trong mch.- Nhng aminoaxit c nhm cacboxyl tham gia to lin kt peptit c gi tn bng cch i ui in thnh

ui yl (xem bi 17.1), aminoaxit ng cui mch cn nhm cacboxyl (ui C) c gi nguyn tn. V d:H2N CH2 CO NH CH(CH3) COOH Glyxylalanin (Gly Ala)

H2N CH(CH3) CO NH CH2 COOH Alanyl glyxin (Ala Gly)


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Bin son v hng dn: PGS.TS Trn HinH2N CH2 CO NH CH CO NH CH2 COOH Glyxyl phenylalanylglyxin

C6H5 CH2 (Gly-Phe-Gly)III- Tnh cht: 1. Tnh cht vt l:

Nhng peptit c phn t khi thp l nhng cht kt tinh tan tt trong nc. Cc peptit c phn t khi lnl nhng cht v nh hnh, to thnh dung dch keo vi nc. 2. Tnh cht ho hc: a, Phn ng thu phn:

Cc peptit b thu phn hon ton trong dung dch axit nng hoc dung dch kim nng cho sn phm cuicng l hn hp cc aminoaxit. Thng thu phn bng dung dch HCl 2N 110 0C trong khong 24 - 72 gi.V d: H+, t0

H2N-CH

R

CO NH -CH CO -

R'

HN-CH

R"

CO - ... nH2O

H2N-CH

R

COOH H2N-CH

R'

COOH H2N-CH

R"

COOH

+

+ + + ....

Cc peptit c th c thu phn khng hon ton nhng on peptit ngn hn nh cc enzim c hiu:- Aminoaxit N -u mch c tch ra khi mch nhenzim aminopeptiaza. V d:aminopeptiaza

H2N-CH

R

CO NH -CH CO -

R'

HN-CH

R"

CO - ... nH2O

H2N-CH

R

COOH H2N-CH

R'

CO HN-CH

R"

COOH

+

+ + ....

- Aminoaxit C-u mch c tch ra khi mch nhenzim cacboxipeptiaza.cacboxipeptiaza

... - HN-CH

R

CO NH-CH CO -

R'

HN-CH

R"

COOH nH2O

... - HN-CH

R

CO HN-CH

R'

COOH H2N-CH

R"

COOH

+

+ + ....

- phn cch mt s lin kt peptit xc nh trong phn t peptit (hoc protein) c th dng cc enzimproteaza nh tripsin, chimotri-psin, pepsin... . Trpin xc tc cho s phn ct lin kt peptit sau gc lysin

hoc arginin. Chimotripsin xc tc cho s phn ct lien kt peptit sau cc gc phenylalanin, tryptophan,tyrosin, leuxin, axit aspactic hoc axit glu tamic. V d:

NHCHCO-......-NHCHCO

R

...-NHCHCOO

R

-H

3NCHCO-...

1

enzim

R1

++

Enzim Aminoaxit u N


19/37

Bin son v hng dn: PGS.TS Trn HinTripsin Lys, ArgChi motripsin Phe, Trp, Tyr Pepsin Phe, Trp, Tyr, Leu, Asp, Glu

b, Phn ng vi 2,4 - initroflobenzen: Tng t aminoaxit, nhm -NH2 ca n v aminoaxit N-u mch phn ng c vi 2,4-

initroflobenzencho dn xut 2,4-initro-phenyl (DNP) mu vng :

O2N F

NO2

H2NCH-CONH-CH-CO- O2N

NO2

NHCHCONH-CHCO-

R R R R

+HF+

Phn ng ny c dng xc nh trt t sp xp cc n v aminoixit trong phn t peptit (Phngphp Sanger). c, Phn ng mu biure

Phn ng mu biure c trng cho lin kt peptit, tt c c peptit c t hai lin kt peptit tr ln u phnng vi dung dch CuSO4 long trong mi trng kim cho dung dch hp cht phc c mu tm hoc tm .

Phn ng biure c dng phntch nh tnh (nhn bit) v phn tch nh lng peptit v prrotein.IV - Tng hp peptit:

Khc vi nhiu loi hp cht hu c khc, cc phn ng tng hp (iu ch) peptit rt phc tp. Khng thtng hp c peptit mong mun nh phn ng trng ngng cc phn t aminoaxit khc nhau, v s to rahn hp cc peptit. V d trng hp n gin nht l ngng t hai phn t aminoaxit khc nhau s to ra 4ipeptit:

Glixin + Alanin-H

2O

Gly-Gly

Ala-Ala

Gly-Ala

Ala-Gly

Do vy tng hp mt peptit c trt t xc nh cc n v aminoaxit trong phn t cn phi bo vnhm amino hay nhm cacboxyl no khi khng cn chngs tham gia phn ng to ra lin kt peptit. Nhmbo v cn tho mn mt s tiu chun sau:

- D gn vo phn t aminoaxit.- Bo v c nhm chc trong iu kin hnh thnh cc lin kt peptit.- D loi ra m khng nh hng n s tn ti ca cc lin kt peptit.

1. Bo v nhm amino:Nhm amino thng c bo v bi nhm benzyloxicacbonyl (C6H5 - CH2O - C -, cn gi l

Ocacbobenzonxi v c k hiu l Cbz)bng cch cho aminoaxit phn ng vi benzyl clofomiat (C6H5-CH2-O-CO-Cl, cacbonbenzoxi clorua) trong dung dch. V d:


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C6H

5CH

2OCOCl H

3NCH

2COO

-C

6H

5CH

2OCONHCH

2COO

H3O

C6H

5CH

2OCONHCH

2COOH

+

+ - dd NaOH

5oC 30 ht

-

+

Benzyloxicacbonylglyxyl

Sau khi tng hp c peptit nhm bo v s c loi ra khi phn t peptit nh phn ng hiro phn:

NHCHCO-...C6H5CH2-OCONHCHCO

R

H2/Pd

C6H

5CH

3 NHCHCO-...HOCONHCHCO

R

CO2 NHCHCO-...H2NCHCO

R

R1

+R1

+

R1

2. Bo v nhm cacboxyl: Nhm cacbonxyl thng c bo v bng cch chuyn thnh metyl hay etyl hoc benzyl este. Nhm ested thu phn hn nhm peptit nn c loi ra khi phn t peptit bng cch thu phn bi dung dch kim:

C6H5CH3 NHCHCO-...HOCONHCHCOR

CO2 NHCHCO-...H2NCHCOR

...- C-NHCH(R)-COOCH3

O

OH/H2O H3O+

...- C-NHCH(R1)-COOH

O

CH3OH

+R1

+R1-

+

Ringnhm benzyloxi (C6H5CH2O-) cn c loi nh phn ng hiro phn:

...- C-NHCH-CO(R)OCH2C

6H

5

O

H2/Pd

...- C-NH(R)CH-COOH

O

C6H

5CH

3+

3. Ngng t cc aminoaxit c bo v

Thc hin phn ng ngng t cc aminoaxit c nhm chc c bo v s thu c peptit mong mun.V d tng hp i peptitthreonylalanin:

C6H

5CH

2OCONHCH-COOH H2NCHCOOCH2C6H5

DDC

-H2O

CH3CHOH CH

3

C6H

5OCONHCH-CO

CH3CHOH

HNCHCOOCH2C

6H

5

CH3

-NH2

DDC

-H2O

-CH2C

6H

5H

2/Pd/C

CH3COOH

H3NCH-CO

CH3CHOH

HNCHCOO

CH3

C6H5CH3 CO2

+

Alanin bo v-COOH

Cbz-Thr-Ala-

+_

2+ +

Threonin bo v

V XC NH CU TRC

xc nh cu trc ca peptit thng thc hin cc bc c bn sau: 1. Xc nh thnh phn cc aminoaxit trong phn t peptit:

Thu phn hon ton peptit thnh hn hp cc aminoaxit (thng thu phn bng dung dch HCl 6N 1100C trong khong 24-72 gi). Sau khi lm sch dung dch thu phn, tch ring tng aminoaxit nh phng


21/37

Ph

C=SNH

CHR

C=O

NH

CHR'

C=O

NHCHR''

C=O

Ph

N=C=S

NH2

CHR

C=O

NH

CHR'

C=O

NHCHR''

C=O

phenyl iso thioxyanat

+

CHR'

C=O

NH

CHR''

C=O

N

O=C

CH

C=S

NHR

Ph

NH2

phenyl thiohydantoin+

Bin son v hng dn: PGS.TS Trn Hinphp sc k. nhn bit tng aminoaxit cn tin hnh sc k thm mt dung dch chun cha hn hp ccaminoaxit bit v c nng xc nh. So snh cc sc k ca dung dch chun s bit c thnh phnv t l tng aminoaxit trong phn t peptit.

2. Xc nh trnh t sp xp cc n v aminoaxit trong phn t peptit: 2.1. Xc nh aminoaxit u N

- Phng php Sanger Cho peptit phn ng vi 2,4-initro-flobenzen thu c dn xut 2,4-initrophenyl ca peptit. Thu phndn xut ny trong mi trng axit thu c hn hp cc aminoaxit v 2,4-initrophenyl ca aminoaxit uN, dn xut DNP ca aminoaxit c th nhn bit c bng cc phng php sc k, t suy ra n vaminoaxit u N:

O2N F

NO2

O2N

NO2

NHCHCONH-CHCO-

O2N NHCHCOOH

NO2

H3N CH-COO

H2NCH-CONH-CH-CO-

R R

R R

+

R R

+

2,4-dinitroflobenzen

HCl, to+

-

N-(2,4-initrophenyl) aminoaxit- Phng php Edman

Cho peptit tc dng vi phenylosothioxionat C6H5N=C=S, nhm NH2 ca n v aminoaxit u N phnng to ra dn xut penylisothicacbamonyl peptit (dn xut phenyl thioure ca peptit), sau cho dn xutthu c tc dng vi HCl trong mitrometan s xy ra s phn ct lin kt peptit gc aminoaxit u N, tothnh peptit ngn hn v phenylthiohiantoin:

HClH2O

peptit phenylthiocacbamoylpeptit peptit ngn hn


22/37

N

CH

CH2

CH2SCH

3

H

N

H

CCH

RO

O

C

N

H

CH2

CH2

O

CO

CHCH

R

CONH2

CH3SCN

+ +

Bin son v hng dn: PGS.TS Trn HinSn phm phenylthiohiantoin c nhn bit nh phng php sc k, trn c s so snh vi cht chun

bit c th suy ra aminoaxit u N, peptit ngn hn c tinh ch v li tip tc thc hin phng phpEdman nhn ra n v aminoaxit u N ca n... 2.2. Xc nh aminoaxit u C

Thu phn peptit nh enzim cacboxipeptiaza

-NH-CHR3-CO-NH-CHR2-CO-CHR1-COO- tidzcacboxypep -NH-CHR3-CO-NH-CHR2-COO-

+-NH3+CHR1-COO-Aminoaxit xut hin u tin trong dung dch chnh l aminoaxit u C. Hn ch ca phng php ny l

enzim cacboxipeptidata khng tch c cc aminoaxit ui C l prolin hoc hiroxiprolin ra khi mchpeptit. 2.3. Thu phn tng phn mch peptit

Thu phn peptit nh cc enzim proteaza (tripsin, chimotripsin, pepsin...) thu c hn hp cc peptit cmch ngn hn; cc peptit ny c tch ring nh phng php sc k, tinh ch sch r xc nh trnh t spxp cc n v aminoaxit trong phn t ca chng theo cc phng php nu trn.

phn ct peptit thnh cc peptit c mch ngn hn cn dng cc tc nhn xian bromua BrCN. Tc nhnny ch phn ct mch peptit sau gc methiomin:

BrCN

homoserin lactoni vi mt mch peptit, nu dng cc xc tc phn ct mch khc nhau s thu c nhng phn on khcnhau. Chng hn phn ct on mch sau:

Phn ct bng trypsin

Ala Leu Gly Met Lys Trp Phe Arg Ala Ala Ser Met Ala Phe Lys

Phn ct bng BrCN


23/37


MT S BI TP V HP CHT CA NIT

Cu 1:( thi HSG quc gia nm 2000-2001) Xut pht t Brombenzen cha 14C v tr 1 v cc ha cht v c cn thit khng cha 14C, hy iu chcc hp cht thm cha 14C v tr 3:

a) anilin b) Iotbenzen c) Axit benzoicCu 2: So snh tnh baz ca cc hp cht sau y: R3N, R2NH, RNH2Gii thch v sao c s sp xp ?

Cu 3: (Chn i HSG Tnh 2006- 2007)Mt pentapeptit (A) khi thu phn hon ton cho 2 mol Gly, 1 mol Ala, 1 mol Val v 1mol Phe. Trong

s thu phn tng phn (A) thy c Ala-Gly, Gly-Ala. A tc dng vi HNO2 khng thy gii phng N2. Xcnh cng thc cu to ca A.Cu 4: Mui C6H5N2

+Cl- (phenyliazoni clorua) c sinh ra khi cho C6H5-NH2 (anilin) tcdng vi NaNO2 trong dung dch HCl nhit thp (0-5

oC). iu ch c 14,05 gam C6H5N2+Cl-

(vi hiu sut 100%), lng C6H5-NH2 v NaNO2 cn dng va lA. 0,1 mol v 0,4 mol. B.0,1 mol v 0,2 mol. C.0,1 mol v 0,1 mol. D.0,1 mol v 0,3 mol.

Cu 5: Cho 8,9 gam mt hp cht hu c X c cng thc phn t C3H7O2N phn ng vi 100 ml dungdch NaOH 1,5M. Sau khi phn ng xy ra hon ton, c cn dung dch thu c 11,7 gam cht rn. Cngthc cu to thu gn ca X l

A. HCOOH3NCH=CH2. B. H2NCH2CH2COOH.C. CH2=CHCOONH4. D. H2NCH2COOCH3.

( thi H 2008)Cu 6: C cc dung dch ring bit sau y:

C6HH5NH3Cl(phenylamoniclorua, H2N-CH2-CH2-CH(NH2)-COOH, ClH3N-CH2-COOH,HOOC-CH2-CH2-CH(NH2)-COOH, H2N-CH2-COONa.

S lng cc dung dch c pH


24/37

Bin son v hng dn: PGS.TS Trn Hin3. (CD3)2CHCHCOO- 4. HOO14CCH2CHCOO-

Hy vit s iu ch cc cht trn

Cu 10: ( thi HSG quc gia - 1997)Khi thy phn hon ton 1 mol polipeptit X thu c 2 mol CH3CH(NH2)COOH (Alanin hay vit tt

l Ala), 1 mol HOOC(CH2)2CH(NH2)COOH (Axit glutamic hay Glu), 1 mol H2N(CH2)4CH(NH2)COOH

(Lysin hay Lys) v 1 mol (Histidin hay His)

Nu cho X phn ng vi 2,4-dinitroflobenzen (k hiu ArF) ri mi thy phn th thu c Ala, Glu, Lys vhp cht :

Mt khc nu thy phn X nh enzim cacboxipeptidaza th thu c Lys v mt tetrapeptit. Ngoi ra khithy phn khng hon ton X cho ta cc dipeptit Ala-Glu, Ala-Ala v His-Ala.

1.Xc nh cng thc cu to v tn ca polipeptit X.2.Sp xp cc amino axit trn theo trt t tng dn pHI, bit cc gi tr pHI l 3,22; 6,00; 7,59 v 9,74.

3.Vit cng thc cu to dng ch yu ca mi aminoaxit trn cc pH bng 1 v 13.4.Di tc dng ca enzim thch hp aminoaxit c th b decacboxyl ha (tch nhm cacboxyl). Vitcng thc cu to cc sn phm decacboxyl ha Ala v His. So snh tnh baz ca cc nguyn t N trongphn t gia hai sn phm . Gii thch.

Cu 11: ( thi HSG quc gia - 2000)t chy 0,2 mol hp cht A thuc loi tp chc thu c 26,2 gam kh CO2; 12,6 gam hi H2O v 2,24 lt

kh N2 (ktc). Nu t chy 1 mol A cn 3,75 mol O2.1.Xc nh cng thc phn t ca A .2.Xc nh cng thc cu to v tn A. Bit rng A c tnh cht lng tnh, phn ng vi axit nitr

gii phng nit; vi ancol etylic c axit lm xc tc to thnh hp cht c cng thc C 5H11O2N. Khi un nngA chuyn thnh hp cht vng c cngthcC6H10N2O2 . Hy vit y cc phng trnh phn ng xy ra

v ghi iu kin (nu c). A c ng phn loi g?Cu 12: ( thi HSG quc gia - 2001)

1.C mt hn hp protit gm pepsin (pHI = 1,1), hemoglobin (pHI = 6,8) v prolamin (pHI = 12,0).Khi tin hnh in di dung dch protit nu trn pH = 7,0 thi c ba vt cht (xem hnh)

Xu t ph t

Cc (+) Cc (-)

A B C

Cho bit mi vt cht c trng cho protit no ? Gii thch.

2.Khi thy phn hon ton 1 mol tripeptit X thu c 2 mol axit glutamic(HOOC(CH2)2CH(NH2)COOH), 1 mol alanin (CH3CH(NH2)COOH) v 1 mol NH3. X khng phn ng vi2,4-dinitroflobenzen v X ch c mt nhm cacboxyl t do. Thy phn X nh enzim cacboxipeptidaza thuc alanin v mt dipeptit Y. Vit cng thc cu to ca X, Y v gi tn chng.

Cu 13: ( thi HSG quc gia - 2002)Thu phn mt protein (protit) thu c mt s aminoaxit c cng thc v pKa nh sau:

Ala : CH3CH(NH2)COOH (2,34; 9,69; Ser : HOCH2CH(NH2)COOH (2,21; 9,15)Asp : HOOCCH2CH(NH2)COOH (1,88; 3,65;9,60)

N

NH

CH2 CH COO

NH-Ar

NNH

CH2 CH COOHNH2


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Bin son v hng dn: PGS.TS Trn HinOrn : H2N[CH2]3CH(NH2)COOH (2,10; 8,90; 10,50)Arg : H2NC(=NH)NH[CH2]3CH(NH2)COOH (2,17; 9,04; 12,48)

ProNH

COOH

(1,99; 10,60)1.Vit tn IUPAC v cng thc Fisher pH I ca Arg, Asp, Orn. Trn mi cng thc hy ghi (trong

ngoc) gi tr pKa bn cnh nhm chc thch hp. Bit nhm -NHC(=NH)NH2 c tn l guanidino.2.Ala v Asp c trong thnh phn cu to ca aspactam (mt cht c ngt cao hn saccaroz ti

160 ln). Thu phn hon ton aspactam thu c Ala, Asp v CH 3OH. Cho aspactam tc dng vi 2,4-dinitroflobenzen ri thu phn th c dn xut 2,4-dinitrophenyl ca Asp v mt sn phm c cng thcC4H9NO2. Vit cng thc Fisher v tn y ca aspactam, bit rng nhm -COOH ca Asp khng cn tdo.

3.Arg, Pro v Ser c trong thnh phn cu to ca nonapeptit bradikinin. Thu phn bradikinin sinh raPro-Pro-Gly ; Ser-Pro-Phe ; Gly-Phe-Ser ; Pro-Phe-Arg ; Arg-Pro-Pro ; Pro-Gly-Phe ; Phe-Ser-Pro. (a) Dngk hiu 3 ch ci (Arg, Pro, Gly,...), cho bit trnh t cc aminoaxit trong phn t bradikinin. (b) Vit cngthc Fisher v cho bit nonapeptit ny c gi tr pHI trong khong no ? ( 6; > 6).Cu 14: ( thi HSG quc gia - 2003)

1.Hp cht A (C5H11O2N) l mt cht lng quang hot. Kh A bng H2 c xc tc Ni s c B(C5H13N) quang hot. Cho B tc dng vi axit HNO2 thu c hn hp gm ancol C quang hot v ancol tert-amylic (2- metyl-2-butanol).

Xc nh cng thc cu to ca A.Dng cng thc cu to, vit phng trnh cc phn ng tothnhB, C v ancol tert-amylic t A.

2.Hp cht A (C5H9OBr) khi tc dng vi dung dch it trong kim to kt ta mu vng. A tc dngvi dung dch NaOH to ra 2 xeton B v C cng c cng thc phn t C5H8O. B, C u khng lm mt mudung dch kalipemanganat lnh, ch c B to kt ta mu vng vi dung dch it trong kim. Cho B tc dngvi CH3MgBr ri vi H2O th c D (C6H12O). D tc dng vi HBr to ra hai ng phn cu to E v F ccng thc phn t C6H11Br trong ch c E lm mt mu dung dch kalipemanganat lnh.

Dng cng thc cu to, vit s phn ng t A to thnh B, C, D, E, F. Vit tn A v D theo danhphp IUPAC.Cu 15: ( thi HSG quc gia - 2005)

L-Prolin hay axit (S)-piroliin-2-cacboxylic c pK1 = 1,99 v pK2 = 10,60. Piroliin (C4H9N) l aminvng no nm cnh.

1. Vit cng thc Fis v cng thc phi cnh ca L-prolin. Tnh pHI ca hp cht ny.2. Tnh gn ng t l dng proton ho H2A+ v dng trung ho HA ca prolin

pH = 2,50.3. Tnh gn ng t l dng eproton ho A v dng trung ho HA ca prolin

pH = 9,70.4. T metylamin v cc ho cht cn thit khc (benzen, etyl acrilat, natri etylat v cc cht v c),

hy vit s iu ch N-metyl-4-phenylpiperiin.Bi 16: ( thi HSG quc gia, Vit Nam - 2007)1. Thy phn hon ton mt hexapeptit M thu c Ala, Arg, Gly, Ile, Phe v Tyr. Cc peptit E (cha

Phe, Arg) v G (cha Arg, Ile, Phe) c to thnh trong s cc sn phm thy phn khng hon ton M.Dng 2,4-dinitroflobenzen xc nh c amino axit Ala. Thy phn M nh tripsin thu c tripeptit A (chaAla, Arg, Tyr) v mt cht B.

a. Xc nh th t lin kt ca cc amino axit trong M.b. Amino axit no c pHI ln nht v amino axit no c pHI nh nht?


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Bin son v hng dn: PGS.TS Trn HinBit cu to chung ca cc amino axit l H2N-CHR-COOH

AA: Ala Arg Gly Ile Phe TyrR : CH3 (CH2)3NHC(=NH)NH2 H CH(CH3)C2H5 CH2C6H5 p-HOC6H4CH22. Isoleuxin c iu ch theo dy cc phn ng sau (A, B, C, D l k hiu cc cht cn tm):

A B C D 3NH IsoleuxinC2H5ONa 2. HCl

Hy cho bit cng thc ca cc cht A, B, C, D v Isoleuxin.Cu 17: ( chon i tuyn QT 2006)Ala, Val, Leu l ch vit tt tn cc aminoaxit thin nhin, cng thc ln lt l CH 3CH(NH2)COOH,

(CH3)2CHCH(NH2)COOH, (CH3)2CHCH2CH(NH2)COOH.1. Vit cc phng trnh phn ng tng hp tripeptit Leu-Ala-Val t cc cht:Ala, Val, Leu, photpho pentaclorua, BOC-Cl (tert-butyloxicacbonyl clorua), ancol benzylic, DCC

(ixiclohexylcacboiimit), axit trifloaxetic, axit axetic, hiro, palai v cacbon.2. C bao nhiu tripeptit c to thnh m mi tripeptit c 3 aminoaxit trn, nu khng s dng

nhm bo v.3. Biu din cng thc phi cnh ca tripeptit Leu-Ala-Val.4. Ghi gi tr pKa vo nhm tng ng v tnh pH I ca tripeptit ny, bit rng pKa1 = = 3,42; pKa2 =

7,94.

CH

Br

CH3CH2 CH3 2252 CHOOC)H(C

KOH.1

2Br

0t


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COO

CHNH2

CH2

COO

COOH

CHNH3

(CH2)3

CH2NH3

OH

H

COO

CHNH3

(CH2)3

CH2NH3

OH

H


MT S BI TP C LI GII

V d 1: Di tc dng ca in trng, aminoaxit di chuyn v pha in cc no khipH < pI, (b) pH > pI v pH = pI ? Gii thch.

Bi gii:

pH < pI: cation A chim u th, nn di chuyn v pha catot, (b) pH > pI : anion C chim u th nn dichuyn v pha anot v (c) khi pH = pI in tch cn bng nn amino axit khng chuyn dch.V d 2: Vit cn bng in ly ca lysin (mt baz) v tnh im ng in ca n.Xem gi tri pKa trong bng

Bi gii: COO

CHNH2

(CH2)3

CH2NH3

OH

H

COO

CHNH2

(CH2)3

CH2NH2(+2) (+1) (0) (-1)

in tch tng cng ca mi dng c ghi trong ngoc n trn, dng c in tch bng khng tn ti giahai dng c pKa tng ng l 8,95 v 10,53. Nh vy pI = (8,95+10,53)/2 = 9,74.

V d 3: Vit cn bng in ly ca axit aspatic v tnh im ng in ca n.Bi gii:

COOH

CHNH3

CH2

COOH

OH

H

COO

CHNH3

CH2

COOH

OH

H

COO

CHNH3

CH2

COO

OH

H

(+1) (0) (-1) (-2)Dng c in tch bng khng tn ti gia hai dng c pKa tng ng l 1,88 v 3,65.Nh vy pI = (1,88 + 3,65)/2 = 2,77.

V d 4: Khi thy phn hon ton 1 mol tripeptit X thu c 2 mol axit glutamic[HOOC(CH2)2CH(NH2)COOH], 1 mol alanin [CH3CH(NH2)COOH] v 1 mol NH3. Cht X khng phn ngvi 2,4-dinitroflobenzen v X ch c mt nhm cacboxyl t do. Thy phn X nh enzim cacboxipeptidaza thu

c alanin v mt dipeptit Y.Vit cng thc cu to ca X, Y v gi tn chng.Bi gii:

Xc nh cu to X v Y :-Thy phn X nh enzim cacboxipeptidaza thu c alanin v mt dipeptit Y aminoaxit C-u mch lAla v nh vy tripeptit X c cu to theo trt t : Glu-Glu-Ala.-X khng phn ng vi 2,4-dinitroflobenzen v X ch c mt nhm cacboxyl t do nhm -NH2 caaminoaxit N-u mch to lactam vi nhm cacboxyl ca Glu th nht.


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Bin son v hng dn: PGS.TS Trn Hin-Khi thy phn hon ton 1 mol tripeptit X thu c 1 mol NH 3 nhm cacboxyl ca Glu th hai tn ti dng amit -CONH2.

Vy X v Y l :

O C

CH2

NH CH

CH2

CO NH CH CO

(CH2)2CONH2

NH CH

CH3

COOH

X :

Glutamolactamylglutaminylalanin

Y :

Glutamolactamylglutamin

O C

CH2

NH CH

CH2

CO NH CH COOH

(CH2)2CONH2

V d 5: Xc nh cng thc cu to v tn ca A(C 3H7O2N). Bit rng A c tnh cht lng tnh, phn ngvi axit nitr gii phng nit; vi ancol etylic c axit lm xc tc to thnh hp cht c cng thc C 5H11O2N.Khi un nng A chuyn thnh hp cht vng c cng thc C6H10N2O2. Hy vit y cc phng trnh phn

ng xy ra v ghi iu kin (nu c). A c ng phn loi g ?Bi gii:

a) Cng thc cu to ca A :A phn ng vi axit nitr gii phng nit A cha nhm -NH2A phn ng vi ancol etylic to C5H11O2N A cha nhm -COOHun nng A to hp cht vng C6H10N2O2 A l -aminoaxitCng thc cu to ca A : CH3CH(NH2)COOH (alanin)

b) Phng trnh phn ng :

2222273 N2

1OH

2

7CO3O

4

15NOHC +++

CH3 CH

NH2

COOH + HONO CH3 CH

OH

COOH + N2 + H2O

CH3 CH

NH2

COOH + C2H5OH CH3 CH

NH3Cl

COOC2H5 + H2OHCl

CH3 CH

NH3Cl

COOH + NH3 CH3 CH

NH2

COOC2H5 + NH4Cl

CH3 CHNH2

COOH + H2O

to2

HN

NHCH3

O

CH3O

(c) A c ng phn quang hc do phn t c nguyn t cacbon bt i :


29/37


H C

CH3

NH2

COOH

H2N C

CH3

H

COOH


30/37


V d 6: Xut pht t brombenzen cha 14 C v tr 1 v cc ho cht v c cn thit khng cha 14 C, hyiu ch cc hp cht thm cha 14 C v tr 3 :

a) Anilin ; b) Iotbenzen ; c) Axit benzoic.Bi gii:

a,

C14

Br

Mgete khan

C14

MgBr

C14

MgBr

CO2

COOMgBr

COOMgBr

H3O

COOH

C14

COOH

HNO3

H2SO

4

C14

COOH

NO2

HOH

+ (1)

+ (2)

++ (3)

+ +(4)


31/37


C14

COOH

NO2

Na2CO

3

C14

NO2

COONa

HOH CO2

C14

NO2

COONa

CaOC14

NO2

Na2CO

3

C14

NO2

C14

NH3Cl

FeCl3

HOH

C14

NH3Cl

NaOH

C14

NH2

NaCl HOH

+ + +(5)

+ NaOH rn + (6)

22

+ 3 Fe + 7 HCl + 3 + 2 (7)

+ + + (8)

b,

C14

NH2

NaNO2

C14

N N

C14

I

N2 KCl

-

C14

N N

-

+ + 2 HCl+

+ NaCl +2HOH

+ KI + +

(9)

(10)

Cl

+ Cl

c,

C14

N N

C14

C N

N2

CuCl

H+ C

14

COOH

NH4

C

14

C N

+ + CuCN-+

+ 2HOH + ++

2

Cl

(11)

(12)

V d 7:( thi HSG quc gia 1997)

Thu phn hon ton 1mol polipeptit X cho ta:2mol CH3 - CH(NH2) - COOH (Alanin hay vit tt l Ala).


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H2N - CH - C - NH - CH - C - NH - CH - C - NH - CH - C - NH - CH - COOH

CH3 CH3O O O ON

N

CH2

H

(CH2)2

COOH

(CH2)2

NH2

Bin son v hng dn: PGS.TS Trn Hin1mol (HOOC - CH2 - CH2 - CH(NH2) - COOH (axit gluconic hay Glu).1mol H2N-(CH2)4-CH(NH2)-COOH (Lizin hay Lis)1mol (Histidin hay His)

Nu cho X tc dng vi 2,4 (NO2)2 C6H3F (k hiu ArF) ri mi thy phn th tm c Ala, Glu,Lys v hp cht

Mt khc nu thu phn X nh enzim cacboxipetidaza th thu c Lys v mt tetrapeptit. Ngoi ra khi thuphn khng hon ton X cho ta cc ipeptit Ala - Glu, Ala-Ala v His- Ala.

1. Xc nh cng thc cu to v tn ca poliptit X.2. Sp xp cc aminoaxit trn theo th t tng dn pH I(pHI c gi l im ng in, ti pH d

aminoaxit tn ti dng ion tng cc trung ho v in tch v khng di chuyn v mt din cc no c).Bit gi tr pHI l 3,22 ; 6,0; 7,59; 9,74.

3. Vit cng thc cu to dng ch yu ca mi aminoaxit trn cc pH bng 1v 13.4. Di tc dng ca enzim thch hp aminoaxit c th b decacboxyl ho (tch nhm cacboxyl). Vit

cng thc cu to ca cc sn phm ecacboxyl ho Ala v His. So snh tnh baz ca cc nguyn t nittrong phn t gia hai sn phm . Gii thch.

Bi gii:1. T s mol v cng thc cu to ca cc aminoaxit suy ra X l mt pentapeptit.

T kt ta thu phn sn phm phn ng gia X v ArF suy ra u N (u cha nhm -NH2 t do) caX l His.

T sn phm thu phn X nh enzim cacboxipeptitdaza suy ra u C (u cha nhm -COOH t do)ca X l Lys.

Khi thu phn khng hon ton X cho cc ipeptit His-Ala, Ala-Ala, Ala-Glu.

Trt t sp xp cc aminoaxit trong mch: His - Ala - Ala - Glu Lys.

Cng thc cu to ca X:

NH

N CH2 CH

NH2

COOH

NH

N CH2 CH COOH

NH Ar


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CH3 - CH - COOH

+NH3

CH3 - CH - COO-

NH2

HOOC - (CH2)

2- CH - COOH

+NH3

-OOC - (CH2)

2- CH - COO-

NH2

N

N

CH2-CH-COOH

H

H

+NH3

+

N

N

CH2-CH-COO-

H

NH2


(Th sinh c th vit cng thc trong nhm - CO NH - gia Glu v Lys c to ra bi nhm COOH v tr ca Glu vi nhm NH2 v tr ca Lys.

1. Th t tng dn pHI:

Glu < Ala < His < Lys

pHI 3.22 6.00 7.59 9.74

Gii thch: tnh axit ca aminoaxit cng ln th gi tr pHI cng nh, tnh baz cng ln th pHI cng ln.

- Glu c pHI nh nht (3.22) v s nhm COOH nhiu hn s nhm NH2. Mun tn ti dng HOOC- (CH2)2 CH - COO phi thm H+ (a v pH thp) nhm -COOH th hai khng phn li.

NH2

- Lys c pHI ln nht (9.74) v s nhm -NH2 nhiu hn s nhm -COOH.

- Ala c pHI = 6.00 v c mt nhm -COOH v mt nhm -NH2.

- His c pHI trung gian gia Ala v Lys, v tuy c s nhm -COOH v - NH2 bng nhau nhng d vngcha N cng l trung tm baz (tuy yu hn -NH2).

3. pH = 1 pH = 13

Ala :

Glu :

His :


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H3N - (CH2)4 - CH - COOH

+NH3

+

H2N - (CH

2)

4- CH - COO-

NH2

CH3

- CH - COOH

NH2

enzim

-CO2

N

N

CH2-CH-COOH

H

NH2

enzim

-CO2

N

N

CH2-CH

2-NH

2

H


Lys:

4.

CH3 CH2 NH2

(c)

(d)

- Tnh baz gim dn: N(a) > N(b) > N(c) > N(d).Gii thch: Tnh baz nguyn t N tng khi mt electron trn n tng. Mt electron N (a) >

N(b) v N(a) lin kt vi gc C2H5 y e, trong khi N (b) nh hng bi gc d vng ht e. Mt e N(c) CSP2 > CSP3ion lng cc

2.

+

+


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NH2O2N

CH2-NH

2CH

2-NH

2 -CH3NH<

Chuyen de Boi Duong Hoc Sinh Gioi Hoa 12

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