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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 intermediates 1 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.
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  • 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).

  • 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

  • 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

  • 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

  • 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').

  • 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

  • 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

  • 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').

  • 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').

  • 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).

  • 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-).