-
27
Introduction
1,3-Dipheylpropan-1,3-diones commonly known as dibenzoylmethanes
occupy an
important place in synthetic organic chemistry. These have been
used as the
intermediates1 for the synthesis of various heterocyclic
compounds such as isoxazoles,
pyrimidines, benzodiazepines etc.
Synthesis of isoxazoles
Simoni et al.2 reported the synthesis of isoxazoles starting
from methyl ketones which on
reaction with diethyl oxalate in presence of sodium ethoxide at
room temperature gave
ethoxyoxalyl derivatives which were further reacted
regiospecifically with an excess of
hydroxylamine hydrochloride in ethanol solution to afford
isoxazoles in good yields
(scheme 1).
Scheme 1.
-
28
Synthesis of pyrimidines
Kuzueva et al.3
reported the synthesis of
(2-hydroxy/2-mercapto)-4-trifluoromethyl-6-
(fluoroalkyl)pyrimidines by dehydration of
4,5-bis(hydroxy)-4-trifluoromethyl-6-
(fluoroalkyl)hexahydropyrimidn-2-ones obtained by reacting ureas
(thioureas) with
di(fluoroalkyl) substituted 1,3-diketones (scheme 2).
Scheme 2.
Synthesis of benzodiazepines
Kumar and Joshi4
reported the synthesis of benzodiazepines which are very
important
heterocyclic compounds as they have attracted attention in the
field of drugs and
pharmaceuticals. Chlorination of
5-(2-ethoxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-
pyrazolo[4,3-d]pyridin-7-one (a) with phosphorus oxychloride
afforded 5-(2-
ethoxyphenyl)-1-methyl-7-chloro-1H-pyrazolo[4,3-d]pyridine (b)
which was further
condensed with -diketones to obtain -diketones (c). These newly
synthesized -
diketones were condensed with o-phenylenediamine in presence of
p-toluene sulphonic
acid to give biologically active 3H-1,5-benzodiazepines (scheme
3).
-
29
Scheme 3.
-Diketones have been found to exhibit various pharmacological
activities which are
briefly described below.
Diana et al.5 reported -diketones (2) to exhibit antiviral
activity.
(2)
Acton et al.6 synthesized retinylidene 1,3-diketones (3) and
found these compounds to
show good antitumor activity.
-
30
(3)
Crouse et al.7 synthesized polyfluoro 1,3-diketones (4) and
found these compounds to act
as systematic insecticides.
(4)
Andrae et al.8 synthesized substituted dibenzoylmethanes (5) and
found these compounds
to protect human lymphoid cells efficiently and hence act as
sunscreen agent.
Singletary et al.9 studied the effect of diferuloylmethane (6;
curcumin) and
dibenzoylmethane (7) on rat mammary DNA adducts and found these
products as breast
cancer chemopreventive agents.
-
31
(6)
(7)
Bennet et al.10
synthesized -diketone acrylate bioesters of pseudomonic acid (8)
and
found these compounds to exhibit antibacterial activity.
Singletary and MacDonald11
found dibenzoylmethane (7) to inhibit benzo[a]pyrene- and
1,6-dinitropyrene-DNA adduct formation in human mammary
epithelial cells.
Nishiyama et al.12
synthesized 1,3-indanones (9) and concluded that these
compounds
exhibit significant antioxidant activity.
(9)
-
32
Tchertanov and Mouscadet13
found ketoenols (10, 11) to inhibit HIV-1 integrase.
Importance of 2-hydroxydibenzoylmethanes/
2-hydroxybenzoylcinnamoylmethanes
Joshi and Wadodkar14
identified 2,2'-dimethoxydibenzoylmethane (12), the only
dibenzoylmethane of natural occurrence, and found it to be a
neuroprotective agent
which prevented the production of reactive oxygen species
(ROS).
(12)
These compounds have been used for the synthesis of flavones, a
sub group of naturally
occurring flavonoids, and other related compounds viz.
3-bromoflavones and 3-
alkylflavones.
Synthesis of flavones
Flavones are mainly synthesized by cyclodehydration of
2-hydroxydibenzoylmethanes
(Scheme 4).
-
33
Various reagents have been used under different conditions which
include hydroiodic
acid15
, conc. sulphuric acid in cold16
, hydrobromic acid in acetic acid17
, potassium
carbonate in acetone18
under refluxing conditions, p-toulenesulphonic acid in
benzene19
,
iodine in dimethylsulphoxide20
, heteropolyacids in toluene21
, potassium hydrogen
sulphate22
and bis-(trichloromehtyl)carbonate23
. Also cyclodehydration using mont. K-
1024
and cupric chloride25
under microwave conditions and using phosphorus pentoxide26
using grinding technique have also been reported.
Synthesis of 3-alkylflavones
3-Alkylflavones have been obtained from
-methyl-2-hydroxydibenzoylmethanes which
in turn have been prepared by C-alkylation of
2-hydroxydibenzoylmethanes. C-alkylation
has been reported using dimethylsulphate in potassium carbonate
and acetone27
,
hexamethylphosphotriamide (HMPT)28
and methyl iodide in presence of fluoride ions29
.
But yield in these methods is low due to the formation of
,-dimethyl product alongwith
o-methylation.
A successful method for selective mono--methylation of 2-
hydroxydibenzoylmethanes was reported by Makrandi and Kumari
using phase transfer
catalysis30
. Reaction of 2-hydroxydibenzoylmethanes with methyl iodide
under these
conditions gave -methyl-2-hydroxydibenzoylmethanes which on
heating with pyridine
hydrochloride gave 3-methylflavones, dealkylation and
cyclodehydration taking place
simultaneously in the same step (Scheme 5).
Scheme 5.
-
34
Synthesis of 3-bromoflavones
Most common method used for the synthesis of 3-bromoflavones
involves bromination of
2-hydroxydibenzoylmethanes to give
-bromo-2-hydroxydibenzoylmethanes followed by
cyclization (Scheme 6).
Scheme 6.
Various reagents have been used for bromination which include
bromine in sodium
acetate-acetic acid buffer31
, bromine in dioxane32
, ammonium bromide in hydrogen
peroxide using phase transfer catalysis33
and ammonium bromide with ammonium
persulphate using grinding technique34
.
Synthesis of styrylchromones
2-Styrylchromones constitute an important class of naturally
occurring flavonoids having
similar structure to that of flavones (2-phenylchromones). These
compounds have been
prepared from 2-hydroxybenzoylcinnamoylmethanes following
similar methods that are
used for the synthesis of flavones (scheme 7).
-
35
Scheme 7.
Various reagents have been used for the cyclodehydration of
2-
hydroxybenzoylcinnamoylmethanes which include sulphuric acid in
acetic acid35
, p-
toluenesulphonic acid in dinethyl sulphoxide36
, iodine in dimethyl sulphoxide under
refluxing37
, p-toluenesulphonic acid under microwave irradiations38
and phosphorus
pentoxide26
under grinding conditions.
Synthesis of 2-hydroxydibenzoylmethanes
Various methods have been reported in the literature for the
synthesis of 2-
hydroxydibenzoylmethanes but the base catalyzed
Baker-Venkataraman rearrangement
of 2-aroyloxyacetopenones is the most convenient one. A brief
description of these
methods is given below:
Kostanecki Method15
. This method involves the condensation of various substituted
2-
alkoxyacetophenones and alkylbenzoates in presence of sodium or
sodamide to give 2-
alkoxydibenzoylmethanes (scheme 8).
Scheme 8.
-
36
Allan-Robinson Method39
. This method involves the heating of appropriately
substituted 2-hydroxyacetophenone with anhydride of aromatic
acid in the presence of its
sodium salt at 180oC to give 2-hydroxydibenzoylmethane (scheme
9).
Teoule et al.40
modified Allan-Robinson method by heating phenol with
ethyl-3-oxo-3-
(3,4,5-trimethoxyphenyl)proanoate to get dibenzoylmethanes
(scheme 10).
Scheme 10.
-
37
via Baker Venkataraman rearrangement
Baker and Mahal & Venkataraman developed synthesis of
2-hydroxydibenzoylmethanes
almost simultaneously by base catalyzed rearrangement of
2-aroyloxyacetophenones.
Baker16
synthesized 2-hydroxydibenzoylmethane from 2-hydroxyacetophenone
by
refluxing it with benzoyl chloride in presence of potassium
carbonate in dry benzene
medium. Benzoylation of 2-hydroxyacetophenone followed by its
rearrangement to 2-
hydroxydibenzoylmethane took place simultaneously in the same
pot (scheme 11).
Scheme 11.
Mahal and Venkataraman41
prepared 2-acetyl-1-naphthobenzoate from 2-acetyl-1-
naphthol and rearranged it to 2-(-benzoylacetyl)-1-naphthol by
reacting it with
sodamide in dry ether (scheme 12).
-
38
After that number of modifications have been reported for
obtaining 2-
hydroxydibenzoylmethanes by Baker-Venkataraman rearrangement of
2-
aroyloxyactetophenone which are briefly described below.
Ullal and Wheeler17
used pulverised sodium in dry ether for rearrangement of 2-
aroyloxyacetophenones to 2-hydroxydibenzoylmethanes (scheme 13)
and later Dunne et
al.42
reported the use of powdered potassium hydroxide in dry pyridine
for this
rearrangement. The later conditions were found to be much
superior for this reaction and
have been used as a general reaction by various workers (scheme
14).
Scheme 13.
Scheme 14.
Seshadri et al.18
synthesized various flavones from 2-hydroxyacetophenones by
heating
them with aroyl chloride or acid anhydride43
in dry acetone in presence of anhydrous
potassium carbonate and resulting 2-hydroxydibenzoymethane
intermediates further got
cyclised in the same pot to give flavones but the yields were
very low and it took longer
times (48-72 hours) for the reaction (scheme 15).
-
39
Banerji and Goomer44
reported the synthesis of 2-hydroxydibenzoylmethanes by
reaction
of substituted 2-hydroxyacetophenones with lithium diisopropyl
amide in tetrahydrofuran
at -25oC and the dianion formed was reacted with aroyl chloride
at -78
oC. 2-
Hydroxydibenzoylmethanes were directly obtained in moderate
yield on acidification
with conc. HCl (scheme 16).
Scheme 16.
Jain et al.19
used phase transfer catalysis for the formation of 2-
hydroxydibenzoylmethanes. Substituted 2-hydroxyacetophenones
were stirred with
substituted aroyl chlorides at 80oC in benzene-aqueous potassium
carbonate biphase
medium in the presence of tetra-n-butylammonium hydrogensulphate
to yield the
required compounds (scheme 17).
-
40
Scheme 17.
Hirao et al.45
reported the conversion of 2-aroyloxyacetophenones to 2-
hydroxydibenzoylmethanes by using sodium hydride in
dimethylsulphoxide under inert
atmosphere at room temperature (scheme 18).
Bansal et al.46
reported the formation of 2-hydroxydibenzoylmethanes from 2-
benzoyloxyacetophenone in methanolic sodium hydroxide by
irradiating the solution
with ultraviolet radiations in nitrogen atmosphere (scheme
19).
-
41
Makrandi et al.47
reported the synthesis of 2-hydroxydibezoylmethanes by
reacting
appropriately substituted 2-hydroxyacetophenones with anhydride
of aromatic acid in the
presence of barium hydroxide in dimethyl sulphoxide medium under
thermal as well as
microwave conditions (scheme 20).
Scheme 20.
Krayushkin et al.48
reported the synthesis of 2-hydroxydibenzoylmethanes by reaction
of
2-aroyloxyacetophenons with potassium t-butoxide in
dimethylformamide at room
temperature (scheme 21).
Scheme 21.
Sharma et al.49
synthesized 2-hydroxydibenzoylmethanes by Baker-Venkataraman
rearrangement of 2-aroyloxyacetophenones in presence of
potassium hydroxide using
grinding technique (scheme 22).
-
42
Some other methods for the synthesis of
2-hydroxydibenzoylmethanes have also been
reported by various workers, but these require tedious
experimental conditions and some
of them are listed below.
Nagarathnam and Cushman50
reported the synthesis of 2-hydroxydibenzoylmethanes
from methyl salicylate by reacting it with
tert-butyldimethylsilyl chloride. The o-silyl
protected ether obtained on reaction with 2-hydroxyacetophenone
in presence of lithium
hexamethyldisilazide (LiHMDS) in THF provided dibenzoylmethane
with 2-hydroxyl
protected. Deprotection with tetra n-butylammonium fluoride gave
2-
hydroxydibenzoylmethane (scheme 23).
Scheme 23.
2-Hydroxydibenzoylmethanes were synthesized by the reaction of
polyanions generated
from 2-hydroxyacetophenones with O-silyloxylated benzoate in
presence of lithium
hexamethyldisilazide (LiHMDS) in THF at -78oC
51 (scheme 24).
-
43
Lee et al.52
synthesized 2-hydroxydibenzoylmethanes by condensation of
various
substituted 2-hydroxyacetophenones with benzoylating reagent,
N-methoxy-N-
methylbenzamide, in presence of two equivalent of lithium
diisdopropylamide in THF for
24 hours (scheme 25).
Synthesis of 2-hydroxybenzoylcinnamoylmethanes
2-Hydroxybenzoylcinnamoylmthanes (13) are the compounds having
the structural
similarity with 2-hydroxydibenzoylmethanes and are used as
intermediates for the
synthesis of 2-styrylchromones.
Gaggad et al.35
reported the synthesis of 2-hydroxybenzoylcinnamoylmethanes by
base
catalyzed Baker-Venkataraman rearrangement of cinnamoyl esters
of substituted 2-
hydroxyacetophenones using potassium hydroxide in pyridine
medium (scheme 26).
-
44
Scheme 26.
Makrandi and Kumari36
reported the synthesis of 2-hydroxybenzoylcinnamoylmethanes
under phase transfer catalyzed conditions.
2-Hydroxyacetophenones and cinnamic
anhydride were stirred in benzene-aqueous potassium carbonate
biphase medium in
presence of tetra-n-butylammonium hydrogensulphate at 70-80oC to
give 2-
hydroxybenzoylcinnamoylmethanes (scheme 27).
Scheme 27.
-
45
Pinto et al.53
reported the synthesis of 2-hydroxybenzoylcinnamoylmethanes by
refluxing
cinnamoyl esters of substituted 2-hydroxyacetophenones with
sodium hydride in dry
tetrahydrofuran (scheme 28).
Scheme 28.
Goel et al.38
reported the synthesis of 2-hydroxybenzoylcinnamoylmethanes by
reacting
appropriately substituted 2-hydroxyacetophenones with cinnamic
anhydride in presence
of barium hydroxide in dimethylsulphoxide medium under microwave
irradiations
(scheme 29).
Scheme 29.
Gomes et al.54
reported the synthesis of 2-hydroxybenzoylcinnamoylmethanes
by
reaction of substituted 2-cinnamoyloxyacetophenones with
potassium hydroxide in dry
dimethylsulphoxide at room temperature (scheme 30).
-
46
Scheme 30.
Sharma et al.55
reported the synthesis of 2-hydroxybenzoylcinnamoylmethanes
by
reaction of 2-cinnamoyloxyacetophenones with potassium hydroxide
using grinding
trechnique (scheme 31).
Scheme 31.
-
47
Present work
2-Hydroxydibenzoylmethanes constitute an important class of
compounds which have
been used as intermediates for the synthesis of flavones,
3-alkylflavones, the compounds
of natural occurrence, 3-bromoflavones and also for the
synthesis of various heterocyclic
compounds such as isoxazoles, pyrimidines, benzodiazepines,
styrylchromones etc.
These -diketones themselves have been found to possess a broad
spectrum of
pharmacological activities and 2,2'-dimethoxydibenzoylmethane
(4) was found to be a
neuroprotective agent and prevented the production of reactive
oxygen species (ROS).
2-Hydroxydibenzoylmethanes are easily obtainable compounds by
base catalyzed
Baker-Venkataraman rearrangement of 2-aroyloxyacetophenones.
These esters are
normally prepared by the reaction of 2-hydroxyacetophenones with
aroyl chlorides or
anhydrides in pyridine under anhydrous conditions. These esters
have also been prepared
by direct condensation of 2-hydroxyacetophenones with
corresponding acids in presence
of phosphorus oxychloride in pyridine medium35
or DCCI.
As now a days, emphasis is being laid to develop eco-friendly
methods for the
synthesis of compounds avoiding the toxic and hazardous
chemicals being used during
the reaction. The use of green solvents, i.e. water and ethanol
as reaction medium is being
encouraged to achieve the greener procedures for the reaction.
But the problem in using
water as reaction medium is that the reactions are quite slow
due to non-homogeneity of
the reaction medium. But, the reaction in aqueous medium can be
carried out effectively
either by carrying them using microwave radiations in which
higher energy is directly
provided to the molecules or by using grinding technique in
which collision frequency
increases because of molecules being in direct contact which has
been described earlier
(Ch.1, p-4). Therefore, it was thought worth to study the
reaction of 2-
hydroxyacetophenones with aroyl chloride or acid anhydride in
aqueous medium using
grinding which could provide a simple eco-friendly procedure for
the synthesis of 2-
aroyloxyacetophenones. But before this, ester formation of
simple phenols was taken up
under grinding conditions in order to achieve the optimum
conditions for ester formation
and potassium carbonate was chosen as a base due to its moderate
basicity.
-
48
A mixture of phenol (5 mmol), benzoyl chloride (5 mmol) and
potassium
carbonate (10 mmol) homogenized with 5 drops of water was ground
in a mortar with a
pestle. The progress of the reaction was monitored by TLC when
phenol was found to
have reacted completely only after 3 min. The reaction mixture
was acidified with conc.
HCl after diluting it with ice cold water and the compound thus
obtained was identified
as phenyl benzoate from its IR which showed absorption at 1726
cm-1
due to C=O
stretching and comparison of m.p. with literature56
value (68oC).
The above reaction was repeated omitting water from the
reaction, but in this case
the reaction was found to have taken place in a sluggish manner
showing tailing on the
TLC and no pure compound could be isolated. Thus, it was
concluded that the presence
of water is necessary to homogenize the reaction mixture.
Scheme 32.
The above reaction was also carried out using benzoic anhydride
in place of
benzoyl chloride under similar conditions and phenyl benzoate
was obtained in 80% yield
(scheme 32). This appears to be a simple and efficient method
for the preparation of
esters in aqueous medium at room temperature in very short
interval of time.
Following above reaction conditions various other phenols were
converted into
corresponding benzoates showing the reaction to be of general
nature and these benzoates
are listed below:
(i) phenyl benzoate
(14)
-
49
(ii) p-cresyl benzoate
(15)
(iii) -naphthyl benzoate
(16)
(iv) -naphthyl benzoate
(17)
(v) resorcinol dibenzoate
(18)
(vi) hydroquinone dibenzoate
(19)
-
50
(vii) phloroglucinol tribenzoate
(20)
Using above reaction conditions,
7-hydroxy-4-methylcoumarin55
(21), prepared by
grinding resorcinol with ethylacetoacetate in presence of
p-toluenesulphonic acid, was
converted into 7-benzoyloxy-4-methylcoumarin (22) in 92% yield
(scheme 33 ).
Scheme 33.
Due to simple nature of the reaction, benzoylation of anilines
was next taken up.
A mixture of aniline (5 mmol), benzoyl chloride (5 mmol) and
potassium carbonate (10
mmol) moist with few drops of water was ground in mortar with
pestle and reaction
mixture on working up as described earlier gave benzanilide in
90% yield.
-
51
Scheme 34.
Following above procedure, other substituted anilines were also
converted into
corresponding N-benzoyl derivatives which are listed below:
(i) benzanilide
(23)
(ii) p-toluanilide
(24)
(iii) p-anisanilide
(25)
N-Tosyl derivatives of aniline are the important compounds that
have been used
as the intermediates during the synthesis of various compounds.
Therefore, tosylation of
anilines using grinding conditions was next taken up. A mixture
of aniline (5 mmol), p-
toluenesulphonyl chloride (5 mmol) and potassium carbonate (10
mmol) moist with a few
drops of water was ground under similar conditions and the
reaction mixture on working
-
52
up gave 4-methyl-N-phenyl-benzenesulphonamide (27; m.p.
101-02oC) in 80-90% yield
whose identity was confirmed by its IR spectrum which showed
absorption at 3324 cm-1
due to N-H stretching, at 1510 cm-1
due to N-H bending, at 1334 and 1161 cm-1
due to
symmetric and asymmetric S=O stretching and comparison of m.p.
with literature60
value (103oC).
Scheme 35.
Following this method other substituted benzene sulphonamides
from substituted anilines
were prepared which are listed below:
(i) 4-methyl-N-phenylbenzenesulphonamide
(27)
(ii) 4-methyl-N-p-tolylbenzenesulphonamide
(28)
-
53
(iii) N-(4-methoxyphenyl)-4-methylbenzenesulphonamide
(29)
After meeting success in benzoylation of phenols, anilines and
formation of
sulphonamides from aniline, the synthesis of
2-aroyloxyacetophenones, the key
intermediates for the synthesis of 2-hydroxydibenzoylmethanes
from 2-
hydroxyacetophenones was next taken up.
A mixture of 2-hydroxyacetophenone (5 mmol), benzoyl chloride (5
mmol) and
potassium carbonate (10 mmol) homogenized with a few drops of
water was ground in a
mortar with a pestle and progress of the reaction was monitored
by TLC and the reaction
was found to be completed in 3 minutes. The reaction mixture was
worked up as
described earlier and 2-benzoyloxyacetophenone (30; m.p.
86-87oC) was obtained in 92%
yield whose identity was confirmed by its IR which showed
absorption at 1736 cm-1
and
1682 cm-1
due to C=O stretching. Its 1H NMR showed signal at 2.54 due to
three
methyl protons and a multiplet between 7.22-8.22 due to nine
aromatic protons. Finally
the identity was confirmed by comparison with authentic sample
(Co-TLC) and
comparison of the melting point with literature61
value (87-88oC).
The above reaction was also repeated using benzoic anhydride in
place of benzoyl
chloride, the reaction took 8 minutes for the completion and
2-benzoyloxyacetophenone
(30) was obtained in 78% yield.
It was preferred to use acid chloride, which is obtained easily
by reaction of acids
with thionyl chloride, over acid anhydride because of
preparation of acid anhydrides,
which are generally obtained by the reaction of acids with POCl3
in pyridine or by
reacting them with DCCI in solvent like DMSO. Moreover, after
the reaction, half of the
acid from anhydride is used up while other half goes waste.
-
54
Scheme 36.
Using above reaction conditions various substituted
2-aroyloxyacetophenones
were prepared which are listed below:
(i) 2-benzoyloxyacetophenone
(30)
(ii) 2-benzoyloxy-5-methylacetophenone
(32)
-
55
(iii) 2-benzoyloxy-4-methoxyacetophenone
(34)
(iv) 2-anisoyloxyacetophenone
(36)
(v) 2-anisoyloxy-5-methylacetophenone
(37)
-
56
(vi) 2-anisoyloxy-4-methoxyacetophenone
(38)
(vii) 2-(o-anisoyloxy)acetophenone
(40)
(viii) 2-(o-anisoyloxy)-5-methylacetophenone
(41)
2-Hydroxyacetophenones were further reacted with cinnamoyl
chloride (42) in
presence of potassium carbonate under grinding conditions as
described above to give 2-
-
57
cinnamoyloxyacetophenones, the required intermediates for the
synthesis of 2-
hydroxybenzoylcinnamoylmethanes which in turn are required for
the synthesis of 2-
styrylchromones.
Differently substituted 2-cinnamoyloxyacetophenones prepared are
listed below:
(i) 2-cinnamoyloxyacetophenone
(ii) 2-cinnamoyloxy-5-methylacetophenone
-
58
(iii) 2-cinnamoyloxy-4-methoxyacetophenone
(45)
This appears to be the efficient procedure for ester formation
and excludes the use
of organic solvents and toxic reagents such as pyridine at any
stage of the reaction and
thus, is an eco-friendly method.
-
59
Experimental
Phenyl benzoate (14)
a) Using benzoyl chloride
A mixture of phenol (0.50 g), benzoyl chloride (0.6 ml) and
potassium carbonate (1.40 g)
homogenized with 5 drops of water was ground in a mortar with a
pestle. The progress of
the reaction was monitored by TLC and it was found to be
completed in 3 min. The
reaction mixture was diluted with ice cold water and acidified
with conc. HCl and the
colourless solid that separated out was filtered, washed with
water and recrystallized
from aqueous ethanol to give the phenyl benzoate (14; 0.90 g),
m.p. 66-67oC (lit.
56 m.p.
68oC).
IR (KBr): 1726 cm-1
(C=O), 1598, 1477 cm-1
(C=C).
b) Using benzoic anhydride
A mixture of phenol (0.50 g), benzoic anhydride (1.10 g) and
potassium carbonate (1.40
g) homogenized with 5 drops of water was ground in a mortar with
a pestle. The progress
of the reaction was checked by TLC and was found to be completed
in 8 min. The
reaction mixture was diluted with ice cold water and acidified
with conc. HCl and the
colourless solid that separated out was filtered, washed with
water and recrystallized
from aqueous ethanol to give phenyl benzoate (14; 0.76 g), m.p.
66-67oC (lit.
56 m.p.
68oC).
p-Cresyl benzoate (15)
A mixture of p-cresol (0.5 ml), benzoyl chloride (0.6 ml) and
potassium carbonate (1.40
g) homogenized with 5 drops of water was ground for 4 min in a
mortar with a pestle.
The completion of the reaction was checked by TLC. The reaction
mixture was diluted
with ice cold water and acidified with conc. HCl. The colourless
solid that separated out
was filtered, washed with water and recrystallized from aqueous
ethanol to give p-cresyl
benzoate (15; 1.00 g), m.p. 55-56oC (lit.
56 m.p. 56
oC).
IR (KBr): 1726 cm-1
(C=O), 1596, 1451 cm-1
(C=C).
-
60
-Naphthyl benzoate (16)
A mixture of -naphthol (0.72 g), benzoyl chloride (0.6 ml) and
potassium carbonate
(1.40 g) homogenized with 5 drops of water was ground for 5 min
in a mortar with a
pestle. The completion of the reaction was checked by TLC. The
reaction mixture was
diluted with ice cold water and acidified with conc. HCl. The
colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
give -naphthyl benzoate (16; 1.14 g), m.p. 54-55oC (lit.56 m.p.
56oC).
IR (KBr): 1735 cm-1
(C=O), 1598, 1450 cm-1
(C=C).
-Naphthyl benzoate (17)
A mixture of -naphthol (0.72 g), benzoyl chloride (0.6 ml) and
potassium carbonate
(1.40 g) homogenized with 5 drops of water was ground for 5 min
in a mortar with a
pestle. The completion of the reaction was checked by TLC. The
reaction mixture was
diluted with ice cold water and acidified with conc. HCl. The
colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
give -naphthyl benzoate (17; 1.10 g), m.p. 106-07oC (lit.56 m.p.
107oC).
IR (KBr): 1731 cm-1
(C=O), 1595, 1449 cm-1
(C=C).
Resorcinol dibenzoate (18)
A mixture of resorcinol (0.55 g), benzoyl chloride (1.2 ml) and
potassium carbonate (1.40
g) homogenized with 5 drops of water was ground for 5 min in a
mortar with a pestle.
The completion of the reaction was checked by TLC. The reaction
mixture was diluted
with ice cold water and acidified with conc. HCl. The colourless
solid that separated out
was filtered, washed with water and recrystallized from aqueous
ethanol to give
resorcinol dibenzoate (18; 1.50 g), m.p. 114-15oC (lit.
56 m.p. 117
oC).
IR (KBr): 1734 cm-1
(C=O), 1596, 1478 cm-1
(C=C).
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61
Hydroquinone dibenzoate (19)
A mixture of hydroquinone (0.55 g), benzoyl chloride (1.2 ml)
and potassium carbonate
(1.40 g) homogenized with 5 drops of water was ground for 5 min
in a mortar with a
pestle. The completion of the reaction was checked by TLC. The
reaction mixture was
diluted with ice cold water and acidified with conc. HCl. The
colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
give hydroquinone dibenzoate (19; 1.20 g), m.p. 196-99oC
(lit.
56 m.p. 199
oC).
IR (KBr): 1730 cm-1
(C=O), 1598, 1451 cm-1
(C=C).
Phloroglucinol tribenzoate (20)
A mixture of phloroglucinol (0.63 g), benzoyl chloride (1.8 ml)
and potassium carbonate
(1.40 g) homogenized with 5 drops of water was ground for 4 min
in a mortar with a
pestle. The completion of the reaction was checked by TLC. The
reaction mixture was
diluted with ice cold water and acidified with conc. HCl. The
colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
give phloroglucinol tribenzoate (20; 1.60 g), m.p. 182-83oC
(lit.
57 m.p. 185
oC).
IR (KBr): 1738 cm-1
(C=O), 1600, 1451 cm-1
(C=C).
7-Hydroxy-4-methylcoumarin (21)
A mixture of resorcinol (1.10 g) and ethylacetoacetate (1.3 ml)
was ground with dry p-
toluene sulphonic acid (1.76 g) in a mortar by pestle for 10 min
when a colour change of
the mixture took place. The reaction mixture was kept at room
temperature for about 20
minutes. The completion of the reaction was checked by TLC and
the reaction mixture
was diluted with ice cold water. The solid that separated out
was filtered at vacuum,
washed with water and recrystallized from ethanol to give
7-hydroxy-4-methylcoumarin
(21; 1.60 g), m.p. 183-84oC (lit.
55 m.p. 184-86
oC).
7-Benzoyloxy-4-methylcoumarin (22)
A mixture of 7-hydroxy-4-methylcoumarin (21; 0.80 g), benzoyl
chloride (0.6 ml) and
potassium carbonate (1.40 g) homogenized with 5 drops of water
was ground for 4 min in
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62
a mortar with a pestle. The completion of the reaction was
checked by TLC. The reaction
mixture was diluted with ice cold water and acidified with conc.
HCl. The colourless
solid that separated out was filtered, washed with water and
recrystallized from aqueous
ethanol to give 7-benzoyloxy-4-methylcoumarin (22; 1.28 g), m.p.
122-23oC.
IR (KBr): 1738 cm-1
(ester, C=O), 1728 cm-1
(coumarin, C=O).
1H NMR (CDCl3): 2.46 (s, 3H, CH3), 6.29 (s, 1H, H-3), 7.20-8.20
(m, 8H, Ar-H).
Benzanilide (23)
A mixture of aniline (0.5 ml), benzoyl chloride (0.6 ml) and
potassium carbonate (1.40 g)
homogenized with 5 drops of water was ground for 4 min in a
mortar with a pestle. The
completion of the reaction was checked by TLC. The reaction
mixture was diluted with
ice cold water and acidified with conc. HCl. The colourless
solid that separated out was
filtered, washed with water and recrystallized from aqueous
ethanol to give benzanilide
(23; 1.10 g), m.p.112-13oC (lit.
58 m.p. 114
oC).
IR (KBr): 3325 cm-1
(N-H), 1642 cm-1
(C=O), 1596, 1488 cm-1
(C=C).
p-Toluanilide (24)
A mixture of toluidine (0.54 g), benzoyl chloride (0.6 ml) and
potassium carbonate (1.40
g) homogenized with 5 drops of water was ground for 3 min in a
mortar with a pestle.
The completion of the reaction was checked by TLC. The reaction
mixture was diluted
with ice cold water and acidified with conc. HCl. The colourless
solid that separated out
was filtered, washed with water and recrystallized from aqueous
ethanol to give p-
toluanilde (24; 0.95 g), m.p. 147-48oC (lit.
58 m.p. 148
oC).
IR (KBr): 3310 cm-1
(N-H), 1647 cm-1
(C=O), 1598, 1490 cm-1
(C=C).
p-Anisanilide (25)
A mixture of p-anisidine (0.63 g), benzoyl chloride (0.6 ml) and
potassium carbonate
(1.40 g) homogenized with 5 drops of water was ground for 5 min
in a mortar with a
pestle. The completion of the reaction was checked by TLC. The
reaction mixture was
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63
diluted with ice cold water and acidified with conc. HCl. The
colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
give p-anisanilide (25; 1.20 g), m.p. 164-65oC (lit.
58 m.p. 169
oC).
IR (KBr): 3318 cm-1
(N-H), 1649 cm-1
(C=O), 1590, 1488 cm-1
(C=C).
p-Toluenesulphonyl chloride (26)
A solution of p-toluenesulphonic acid (10.00 g) and thionyl
chloride (15 ml) was refluxed
in a round bottom flask fitted with a water condenser carrying a
calcium chloride guard
tube on a water bath for one hr until the evolution of SO2 and
HCl almost ceased. Excess
of thionyl chloride was distilled off under reduced pressure and
the solid residue thus
obtained was p-toluenesulphonyl chloride (26; 10.80 g), m.p.
66-67oC (lit.
59 m.p. 69
oC).
4-Methyl-N-phenylbenzenesulphonamide (27)
A mixture of aniline (0.5 ml), p-toluenesulphonyl chloride (26;
0.95 g) and potassium
carbonate (1.40 g) homogenized with 5 drops of water was ground
in a mortar with a
pestle. The progress of the reaction was monitored by TLC and
the reaction was found to
be completed in 5 min. The reaction mixture was diluted with ice
cold water and acidified
with conc. HCl and the colourless solid that separated out was
filtered, washed with water
and recrystallized from aqueous ethanol to give
4-methyl-N-phenylbenzenesulphonamide
(27; 0.96 g), m.p. 101-02oC (lit.
60 m.p. 103
oC).
IR (KBr): 3234 cm-1
(N-H), 1596, 1463 cm-1
(C=C), 1510 cm-1
(N-H bend.), 1334, 1161
cm-1
(S=O).
4-Methyl-N-p-tolylbenzenesulphonamide (28)
A mixture of p-toluidine (0.54 g), p-toluenesulphonyl chloride
(26; 0.95 g) and potassium
carbonate (1.40 g) homogenized with 5 drops of water was ground
for 4 min in a mortar
with a pestle. The completion of the reaction was checked by
TLC. The reaction mixture
was diluted with ice cold water and acidified with conc. HCl.
The colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
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64
give 4-methyl-N-p-tolylbenzenesulphonamide (28; 1.00 g), m.p.
117-18oC (lit.
60 m.p.
118oC).
IR (KBr): 3251 cm-1
(N-H), 1598, 1483 cm-1
(C=C), 1510 cm-1
(N-H bend.), 1339, 1158
cm-1
(S=O).
N-(4-Methoxyphenyl)-4-methylbenzenesulphonamide (29)
A mixture of p-anisidine (0.60 g), p-toluenesulphonyl chloride
(26; 0.95 g) and potassium
carbonate (1.40 g) homogenized with 5 drops of water was ground
for 6 min in a mortar
with a pestle. The completion of the reaction was checked by
TLC. The reaction mixture
was diluted with ice cold water and acidified with conc. HCl.
The colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
give N-(4-methoxyphenyl)-4-methylbenzenesulphonamide (29; 1.10
g), m.p. 111-12oC
(lit.60
m.p. 114oC).
IR (KBr): 3268 cm-1
(N-H), 1598, 1466 cm-1
(C=C), 1510 cm-1
(N-H bend.), 1332, 1160
cm-1
(S=O).
2-Benzoyloxyacetophenone (30)
Method A: Using benzoyl chloride
A mixture of 2-hydroxyacetophenone (0.6 ml), benzoyl chloride
(0.6 ml) and potassium
carbonate (1.40 g) homogenized with 5 drops of water was ground
for 3 min in a mortar
by a pestle and completion of the reaction was checked by TLC.
The reaction mixture
was diluted with ice cold water and acidified with conc. HCl and
the colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
give 2-benzoyloxyacetophenone (30; 1.02 g), m.p. 86-87oC
(lit.
61 m.p. 87-88
oC).
IR (KBr): 1736 cm-1
(C=O, ester), 1682 cm-1
(C=O, ketone).
1H NMR (CDCl3): 2.54 (s, 3H, CH3), 7.22-8.22 (m, 9H, H-3, H-4,
H-5, H-6, H-2', H-3',
H-4', H-5', H-6').
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65
Method B: Using benzoic anhydride
A mixture of 2-hydroxyacetophenone (0.6 ml), benzoic anhydride
(1.13 g) and potassium
carbonate (1.40 g) homogenized with 5 drops of water was ground
for 8 min in a mortar
by a pestle and completion of the reaction was checked by TLC.
The reaction mixture
was diluted with ice cold water and acidified with conc. HCl and
the colourless solid that
separated out was filtered, washed with water and recrystallized
from aqueous ethanol to
give 2-benzoyloxyacetophenone (30; 0.86 g), m.p. 86-87oC
(lit.
61 m.p. 87-88
oC).
IR (KBr): 1736 cm-1
(C=O, ester), 1682 cm-1
(C=O, ketone).
p-Tolylacetate
A mixture of p-cresol (25 ml), acetic anhydride (50 ml) and
anhydrous sodium acetate
(40 g) was refluxed in a 250 ml round bottom flask fitted with a
calcium chloride guard
tube for 4 hr. The reaction mixture was poured over crushed ice
and left overnight,
extracted with ethyl acetate, organic layer was washed with
water, dried over calcium
chloride and solvent was removed by distillation. The residue
was distilled to give p-
tolylacetate as colourless liquid (17 ml), b.p. 210-12oC
(lit.
62 b.p. 212-13
oC).
2-Hydroxy-5-methylacetophenone (31)
Powdered aluminium chloride (30 g) was added to p-tolylacetate
(9.6 ml) in a 250 ml
round bottom flask fitted with calcium chloride guard tube at
0oC. The temperature was
slowly raised to 120oC in oil bath in 30 min and maintained at
160
oC for 2 hr. Aluminium
chloride complex was decomposed with crushed ice (150 g) and
hydrochloric acid (15
ml). The solid that separated out was filtered, washed with
water, dried and recrystallized
from petroleum ether to give 2-hydroxy-5-methylacetophenone (31;
10 g) as light brown
needles, m.p. 52-53oC (lit.
63 m.p. 52
oC).
2-Benzoyloxy-5-methylacetophenone (32)
A mixture of 2-hydroxy-5-methylacetophenone (31; 0.75 g),
benzoyl chloride (0.6 ml)
and potassium carbonate (1.40 g) homogenized with 5 drops of
water was ground for 4
min in a mortar with a pestle and completion of the reaction was
checked by TLC. The
reaction mixture was diluted with ice cold water and acidified
with conc. HCl and the
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66
colourless solid that separated out was filtered, washed with
water and recrystallized
from aqueous ethanol to give 2-benzoyloxy-5-methylacetophenone
(32; 1.14 g), m.p. 86-
87oC (lit.
64 m.p. 87-88
oC).
IR (KBr): 1736 cm-1
(C=O, ester), 1682 cm-1
(C=O, ketone).
1H NMR (CDCl3): 2.39 (s, 3H, CH3) 2.51 (s, 3H, COCH3), 7.09-8.21
(m, 8H, H-3, H-4,
H-6, H-2', H-3', H-4', H-5', H-6').
2,4-Dihydroxyacetophenone
Anhydrous zinc chloride (33 g) was dissolved in glacial acetic
acid (32 ml). To the hot
mixture at 1100C, dry resorcinol (22 g) was added with stirring
and the solution was
heated on sand bath at 140-450C for 20 min. Dilute hydrochloric
acid (1:1, 100 ml) was
added to the reaction mixture and the resulting solution was
cooled, and the solid that
separated out was filtered, washed with water and recrystallized
from hot dilute
hydrochloric acid (1:1) to give 2,4-dihydroxyacetophenone as
yellow needles (22 g), m.p.
145-47oC (lit.
65 m.p. 147
oC).
2-Hydroxy-4-methoxyacetophenone (33)
A solution of 2,4-dihydroxyacetophenone (15 g) in acetone (250
ml) in a 500 ml round
bottom flask was refluxed with anhydrous potassium carbonate (40
g) and
dimethylsulphate (10.0 ml) on a water bath using water condenser
and calcium chloride
guard tube for 1 hr. The acetone solution was filtered and
residue was washed with
acetone. The solvent was removed from combined acetone solution
by distillation, water
(400 ml) was added to the residue and solution was cooled in ice
bath. The solid that
separated out was filtered, washed with water and dried. The dry
solid on crystallization
from diethyl ether-petroleum ether gave
2-hydroxy-4-methoxyacetophenone (33; 13 g) as
long needles, m.p. 50-510C (lit.
66 m.p. 52-53
oC).
2-Benzoyloxy-4-methoxyacetophenone (34)
A mixture of 2-hydroxy-4-methoxyacetophenone (33; 0.85 g),
benzoyl chloride (0.6 ml)
and potassium carbonate (1.40 g) homogenized with 5 drops of
water was ground for 5
min in a mortar with a pestle and completion of the reaction was
checked by TLC. The
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67
reaction mixture was diluted with ice cold water and acidified
with conc. HCl and the
colourless solid that separated out was filtered, washed with
water and recrystallized
from aqueous ethanol to give 2-benzoyloxy-4-methoxyacetophenone
(34; 1.14 g), m.p.
87-88oC (lit.
67 m.p. 85-86
oC).
IR (KBr): 1734 cm-1
(C=O, ester), 1686 cm-1
(C=O, ketone).
1H NMR (CDCl3): 2.46 (s, 3H, COCH3), 3.90 (s, 3H, OCH3), 6.71
(s, 1H, H-3), 7.04-
8.12 (m, 7H, H-5, H-6, H-2', H-3', H-4', H-5', H-6').
p-Anisoyl chloride (35; 4-methoxybenzoylchloride)
A mixture of anisic acid (10 g) and thionyl chloride (15 ml) was
refluxed in a 100 ml
round bottom flask fitted with a water condenser carrying a
calcium chloride guard tube
on a water bath for one hr until the evolution of SO2 and HCl
gases almost ceased. Excess
of thionyl chloride was distilled off from the reaction mixture
under reduced pressure and
the residue was further distilled under reduced pressure to give
p-anisoyl chloride as
colourless liquid (35; 6.0 ml), b.p. 129-31oC/11 mm (lit.
68 b.p. 131
oC/11 mm).
2-Anisoyloxyacetophenone (36)
A mixture of 2-hydroxyacetophenone (0.6 ml), p-anisoyl chloride
(35; 0.7 ml) and
potassium carbonate (1.40 g) homogenized with 5 drops of water
was ground for 3 min in
a mortar by a pestle and completion of the reaction was checked
by TLC. The reaction
mixture was diluted with ice cold water and acidified with conc.
HCl and the colourless
solid that separated out was filtered, washed with water and
recrystallized from ethanol to
give 2-anisoyloxyacetophenone (36; 1.60 g), m.p. 114-15oC
(lit.
69 m.p. 113-14
oC).
IR (KBr): 1726 cm-1
(C=O, ester), 1682 cm-1
(C=O, ketone).
1H NMR (CDCl3): 2.53 (s, 3H, CH3), 3.88 (s, 3H, OCH3), 6.99 (d,
2H, J = 8.04 Hz, H-
3', H-5'), 7.22 (d, 1H, J = 8.04 Hz, H-3), 7.34 (t, 1H, J = 7.00
& 7.08 Hz, H-4), 7.56 (t,
1H, J = 6.92 & 7.20 Hz, H-5), 7.84 (d, 1H, J = 7.24 Hz,
H-6), 8.16 (d, 2H, J = 8.04 Hz,
H-2', H-6').
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68
2-Anisoyloxy-5-methylacetophenone (37)
A mixture of 2-hydroxy-5-methylacetophenone (31; 0.75 g),
p-anisoyl chloride (35; 0.7
ml) and potassium carbonate (1.40 g) homogenized with 5 drops of
water was ground for
5 min in a mortar with a pestle and completion of the reaction
was checked by TLC. The
reaction mixture was diluted with ice cold water and acidified
with conc. HCl and the
colourless solid that separated out was filtered, washed with
water and recrystallized
from aqueous ethanol to give 2-anisoyloxy-5-methylacetophenone
(37; 1.38 g), m.p. 114-
15oC (lit.
70 m.p. 116
oC).
IR (KBr): 1725 cm-1
(C=O, ester), 1682 cm-1
(C=O, ketone).
1H NMR (CDCl3): 2.4 (s, 3H, CH3), 2.5 (s, 3H, COCH3), 3.89 (s,
3H, OCH3), 6.99 (d,
2H, J = 8.64 Hz, H-3', H-5'), 7.11 (d, 1H, J = 8.16 Hz, H-3),
7.36 (d, 1H, J = 7.80 Hz, H-
4), 7.64 (s, 1H, H-6), 8.16 (d, 2H, J = 8.64 Hz, H-2',
H-6').
2-Anisoyloxy-4-methoxyacetophenone (38)
A mixture of 2-hydroxy-4-methoxyacetophenone (33; 0.83 g),
p-anisoyl chloride (35; 0.7
ml) and potassium carbonate (1.40 g) homogenized with 5 drops of
water was ground for
5 min in a mortar with a pestle and completion of the reaction
was checked by TLC. The
reaction mixture was diluted with ice cold water and acidified
with conc. HCl and the
colourless solid that separated out was filtered, washed with
water and recrystallized
from aqueous ethanol to give 2-anisoyloxy-4-methoxyacetophenone
(38; 1.30 g), m.p.
85-85oC (lit.
70 m.p. 84
oC).
IR (KBr): 1728 cm-1
(C=O, ester), 1674 cm-1
(C=O, ketone).
1H NMR (CDCl3): 2.48 (s, 3H, COCH3), 3.88, 3.89 ( each s, 6H,
2OCH3), 6.71 (s, 1H,
H-3), 6.85 (d, 1H, J = 7.64 Hz, H-5), 6.99 (d, 2H, J = 7.48 Hz,
H-3', H-5'), 7.88 (d, 1H, J
= 8.20 Hz, H-6), 8.16 (d, 2H, J = 7.48 Hz, H-2', H-6').
o-Anisoyl chloride (39; 2-methoxybenzoyl chloride)
A mixture of 2-methoxybenzoic acid (10 g) and thionyl chloride
(15 ml) was refluxed in
a round bottom flask fitted with a water condenser carrying a
calcium chloride guard tube
-
69
on a water bath for one hr until the evolution of SO2 and HCl
gases almost ceased. Excess
of thionyl chloride was distilled off from the reaction mixture
under reduced pressure and
the residue was further distilled to give o-anisoyl chloride as
colourless liquid (39; 6.5
ml), b.p. 252-53oC (lit.
68 b.p. 253-54
oC).
2-(o-Anisoyloxy)acetophenone (40;
2-(2-mehoxybenzoyloxy)acetophenone))
A mixture of 2-hydroxyacetophenone (0.6 ml), o-anisoyl chloride
(39; 0.75 ml) and
potassium carbonate (1.40 g) homogenized with 5 drops of water
was ground for 5 min in
a mortar with a pestle and completion of the reaction was
checked by TLC. The reaction
mixture was diluted with ice cold water and acidified with conc.
HCl and the colourless
solid that separated out was filtered, washed with water and
recrystallized from aqueous
ethanol to give 2-(o-anisoyloxy)acetophenone (40; 1.17 g), m.p.
76-77oC (lit.
71 m.p.
78oC).
IR (KBr): 1744 cm-1
(C=O, ester), 1666 cm-1
(C=O, ketone).
1H NMR (CDCl3): 2.55 (s, 3H, COCH3), 3.9 (s, 3H, OCH3),
7.01-7.59 (m, 6H, H-3, H-
4, H-5, H-3', H-4', H-5'), 7.82 (dd, 1H, J = 7.80 & 1.64 Hz,
H-6'), 8.10 (dd, 1H, J = 7.72
& 1.76 Hz, H-6).
2-(o-Anisoyloxy)-5-methylacetophenone (41)
A mixture of 2-hydroxy-5-methylacetophenone (31; 0.75 g),
o-anisoyl chloride (39; 0.75
ml) and potassium carbonate (1.40 g) homogenized with 5 drops of
water was ground for
4 min in a mortar by a pestle and completion of the reaction was
checked by TLC. The
reaction mixture was diluted with ice cold water and acidified
with conc. HCl and the
colourless solid that separated out was filtered, washed with
water and recrystallized
from aqueous ethanol to give
2-(o-anisoyloxy)-5-methylacetophenone (41; 1.20 g), m.p.
111-13oC (lit.
72 m.p. 112
oC).
IR (KBr): 1744 cm-1
(C=O, ester), 1690 cm-1
(C=O, ketone).
1H NMR (CDCl3): 2.39 (s, 3H, CH3), 2.54 (s, 3H, COCH3), 3.84 (s,
3H, OCH3), 6.97-
7.62 (m, 5H, H-3, H-4, H-3', H-4', H-5'), 8.00 (dd, 1H, J = 7.80
& 1.80 Hz, H-6), 8.08
(dd, 1H, J = 7.72 & 1.76 Hz, H-6').
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70
Cinnamoyl Chloride (42)
A mixture of cinnamic acid (10 g) and thionyl chloride (15 ml)
was refluxed in a round
bottom flask fitted with a water condenser carrying a calcium
chloride guard tube on a
water bath for one hr until the evolution of SO2 and HCl gases
almost ceased. Excess of
thionyl chloride was distilled off from the reaction mixture
under reduced pressure and
the residue was further distilled under reduced pressure to give
cinnamoyl chloride as
colourless liquid (42; 8.0 ml), b.p.130-31oC/11 mm (lit.
68 b.p. 131
oC/11 mm).
2-Cinnamoyloxyacetophenone (43)
A mixture of 2-hydroxyacetophenone (0.6 ml), cinnamoyl chloride
(42; 0.7 ml) and
potassium carbonate (1.40 g) homogenized with 5 drops of water
was ground for 3 min in
a mortar by a pestle and completion of the reaction was checked
by TLC. The reaction
mixture was diluted with ice cold water and acidified with conc.
HCl and the colourless
solid that separated out was filtered, washed with water and
recrystallized from aqueous
ethanol to give 2-cinnamoyloxyacetophenone (43; 1.20 g), m.p.
75-76oC (lit.
71 m.p. 76-
77oC).
IR (KBr): 1720 cm-1
(C=O, ester), 1682 cm-1
(C=O, ketone), 1636 cm-1
(C=C).
1H NMR (CDCl3): 2.55 (s, 3H, CH3), 6.67 (d, 1H, J = 16.00 Hz,
CH=CH- ), 7.18
(dd, 1H, J = 8.08 & 0.96 Hz, H-3), 7.32 (td, 1H, J = 7.64
& 1.60 Hz, H-4), 7.36-7.64 (m,
6H, H-5, H-2', H-3', H-4', H-5', H-6'), 7.82 (dd, 1H, J = 7.76
& 1.60 Hz, H-6), 7.89 (d,
1H, J = 16.00 Hz, -CH=CH-).
2-Cinnamoyloxy-5-methylacetophenone (44)
A mixture of 2-hydroxy-5-methylacetophenone (31; 0.75 g),
cinnamoyl chloride (42; 0.7
ml) and potassium carbonate (1.40 g) homogenized with 5 drops of
water was ground for
4 min in a mortar by a pestle and completion of the reaction was
checked by TLC. The
reaction mixture was diluted with ice cold water and acidified
with conc. HCl and the
colourless solid that separated out was filtered, washed with
water and recrystallized
from aqueous ethanol to give 2-cinnamoyloxy-5-methylacetophenone
(44; 1.26 g), m.p.
72-73oC (lit.
73 m.p. 72
oC).
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71
IR (KBr): 1728 cm-1
(C=O, ester), 1682 cm-1
(C=O, ketone), 1636 cm-1
(C=C).
1H NMR (CDCl3): 2.36 (s, 3H, CH3), 2.53 (s, 3H, COCH3), 6.66 (d,
1H, J = 16.00 Hz,
-CH=CH- ), 7.06 (d, 1H, J = 8.20 Hz, H-3), 7.32 (dd, 1H, J =
8.20 & 1.96 Hz, H-4), 7.3-
7.57 (m, 5H, H-2', H-3', H-4', H-5', H-6'), 7.60 (d, 1H, J =
1.88 Hz, H-6), 7.87 (d, 1H, J =
16.00 Hz, -CH=CH-).
2-Cinnamoyloxy-4-methoxyacetophenone (45)
A mixture of 2-hydroxy-4-methoxyacetophenone (33; 0.83 g),
cinnamoyl chloride (42;
0.7 ml) and potassium carbonate (1.40 g) homogenized with 5
drops of water was ground
for 5 min in a mortar with a pestle and completion of the
reaction was checked by TLC.
The reaction mixture was diluted with ice cold water and
acidified with conc. HCl and
the colourless solid that separated out was filtered, washed
with water and recrystallized
from aqueous ethanol to give
2-cinnamoyloxy-4-methoxyacetophenone (45; 1.40 g), m.p.
87-88oC (lit.
72 m.p. 90
oC).
IR (KBr): 1728 cm-1
(C=O, ester), 1680 cm-1
(C=O, ketone), 1636 cm-1
(C=C).
1H NMR (CDCl3): 2.50 (s, 3H, COCH3), 3.82 (s, 3H, OCH3), 6.66
(d, 1H, J = 15.95 Hz,
CH=CH- ), 6.88 (d, 1H, J = 2.44 Hz, H-3), 6.82 (dd, 1H, J = 8.80
& 2.44 Hz, H-5),
7.37-7.58 (m, 5H, H-2', H-3', H-4', H-5', H-6'), 7.85 (d, 1H, J
= 8.8 Hz, H-6), 7.89 (d, 1H,
J = 15.95 Hz, -CH=CH-).