Title of Invention

"AN IMPROVED PROCESS FOR THE PREPARATION OF 2-(ARYL-1-HYDROXY METHYLENE)CYCLOALKANONES"

Abstract

ABSTRACT Title: An Improved process for the preparation of 2- (aryl-l-hydroxy methylene) cydoalkanones which comprises; reacting silyl enol ether derivative of cydoalkanone An improved process for the preparation of 2- (aryh l-hydroxy methylene) cydoalkanones which comprises; reacting silyi enol ether derivative of cydoalkanone of formula 2 with aromlatlc aldehydes in presence of a solid super-acid catalyst such as herein described, and a chlorinated solvent such as herein described, at ambient temperature in an inert atmosphere for a period ranging from 24 to 52 hours, filtering the reaction mixture to recover the super-acid catalyst, washing the filtrate with water, drying filtrate over a dehydrant, removing the chlorinated solvent under reduced pressure and recovering the product by column chromatography using an organic solvent as an eluent, to get the pure monabdditive 2-(aryl-l-hydroxy methylene) cydoalkanones of formula 1.

Full Text

This invention relates to an improved process for the preparation of 2-(aryl-1-hydroxy;methylene) cycloalkanones. More particularly it relates to the preparation of the monoadditive 2(aryl-l-hydroxy) methylene cycloalkanones of high regioselectivity having general formula 1 given in the drawing accompanying this specification wherein R = nil, -CH2-, -CH(CH3)-; X = cyano, nitro and hydroxy, synthesised from compound having general formula 2 given in the drawing accompanying this specification wherein R = nil, -CH2-, -CH(CH3)-. The compounds prepared by the process of this invention are useful for the preparation of mesogens that would find applications in the synthesis of side chain liquid crystalline polymers. In particular, this invention describes a process for the preparation of monoadditive phenyl-1-hydroxy methylene cycloalkanones, that offer high regio-selectivity. Mesogens are moieties which form part of the polymeric structure in liquid crystalline polymers. If the mesogens form part of the backbone of the polymers, then the polymers are known as main chain liquid crystalline polymers and if these are present as pendant groups along the backbone of the polymers, then the polymers are referred to as side chain liquid crystalline polymers. The mesogens prepared as per the process of this invention are useful for the synthesis of side chain liquid crystalline polymers that could be used for non¬linear optical applications. The hitherto known processes for the preparation of phenyl-1-hydroxy methylene cycloalkanones involve the reaction of cycloalkanones with aromatic aldehydes in the presence of a base in a suitable solvent. These processes do not offer any regio selectivity to obtain mono addition product' and bis condensed products are obtained. Another known process that offers regio selectivity to give mono addition product involves the reaction of cyclohexane silyl enol ether with aromatic aldehydes in the presence of titanium tetrachloride. This reaction offers exclusively mono addition product. The process however suffers from the following disadvantages : 1. Equimolar amount of titanium tetrachloride needs to be added, though the function of titanium tetrachloride is that of a Lewis acid catalyst. 2. The catalyst, titanium tetrachloride is hygroscopic and hazardous to handle. 3. The catalyst cannot be recovered at the end of the reaction giving rise to disposal and environmental hazards. 4. The reaction is carried out at -78°C. It is difficult to maintain this reaction condition in the laboratory. The object of the present invention is to provide an improved process for the preparation of 2-(aryl-1-hydroxy methylene) cycloalkanones that eliminates the above mentioned disadvantages in the hitherto known process. Another object of the present invention is to provide a process in which catalyst used in the process of this invention can be recovered and reused. Accordingly, the present invention provides an improved process for the preparation of 2-(aryl-1-hydroxy methylene) cycloalkanones which comprises; reacting silyl enol ether derivative of cycloalkanone of formula 2 with aromiatic aldehydes in presence of a solid super-acid catalyst such as herein described, and a chlorinated solvent such as herein described, at ambient temperature in an inert atmosphere for a period ranging from 24 to 52 hours, filtering the reaction mixture to recover the super-acid catalyst, washing the filtrate with water, drying filtrate over a dehydrant, removing the chlorinated solvent under reduced pressure and recovering the product by column chromatography using an organic solvent as an eluent, to get the pure monabdditive 2-(aryl-l-hydroxy methylene) cycloalkanones of formula 1. In one of the embodiment of the present inveniton the silyl enol ether used may be such as silyl enol ether of cyclopentene, cyclohexene and 4-cyano benzaldehyde, 4-nitro benzaldehyde, 4-hydroxy benzaldehyde. In yet another feature of the invention, the inert atmosphere may be maintained by using inert gas like nitrogen or argon. According to yet another feature of the invention, the aliphatic chlorinated solvent used may be such as dichloromethane, chloroform, carbon tetrachloride, tetrachloroethane. According to yet another feature of the invention, the solid super-acid catalyst chosen is sulphated zirconia. According to yet another feature of the invention, the dehydrant used to dry the washed product is may be such as sodium sulphate, magnesium sulphate and calcium chloride. The invention is described with reference to the examples given below which are illustrative in nature and should not be construed to limit the scope of this invention. Example 1 The 1-trimethyl silyloxy-1-cyclohexene is prepared by the known process and is described first. 32.6 gram of 1-trimethyl silyl chloride and 60.6 gram of triethylamine in 100 ml dry dimethyl formamide and 24.5 gram of cyclohexanone were stirred together in an inert atmosphere. The reaction mixture was refluxed for 6 hours. The reaction was then cooled to ambient temperature and diluted with 2 00 ml of pentane, washed with 3 00 ml of cold aqueous sodium bicarbonate. The organic layer was then washed with cold 1.5 N hydrochloric acid. The resulting organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure and distilled under vacuum to get 32 gram of colourless 1-trimethyl silyloxy-1-cyclohexene. 1.36 gram of 1-trimethyl silyloxy-1-cyclohexene was mixed with 0.95 gram of 4-cyano benzaldehyde and 0.24 gram of sulphated zirconia in 40 ml of dichloromethane. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 35°C for 40 hours. The reaction mixture was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over sodium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (5:1 V/V) as an eluent to get the pure 2-(4-cyano phenyl-1-hydroxy methylene) cyclohexanone. The yield obtained was 1.4 gram. Example 2 0.68 gram of 1-trimethyl silyloxy-1-cyclohexene was mixed with 0.54 gram of 4-nitro benzaldehyde and 0.12 gram of sulphated zirccr.ia in 20 ml of dichloromethane. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 3 5°C for 4 8 hours. The reaction mixture was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over sodium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chrorr.atographed through a silica gel column using a petroleum ethei- : acetone mixture (5:1 V/V) as an eluent to get the pure 2-(4-nitro phenyl-1-hydroxy methylene) cyclohexanone. The yield obtained was 0.76 gram. Example 3 0.68 gram of 1-trimethyl silyloxy-1-cyclohexene was mixed with 0.44 gram of 4-hydroxy benzaldehyde and 0.12 gram of sulphated zirconia in 20 ml of dichloromethane. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 35°C for 48 hours. The reaction mass was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over anhydrous magnesium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (5:1 V/V) as the eluent to get the pure 2-(4-hydroxy phenyl-1-hydroxy methylene) cyclohexanone. The yield obtained was 0.76 gram. Example 4 The 1-trimethyl silyloxy-1-cyclopentene is prepared by the known process and is described first. 32.6 gram of 1-trimethyl silyl chloride and 60.6 gram of triethylamine in 100 ml dry dimethyl formamide and 21.0 gram of cyclopentanone were stirred together in an inert atmosphere. The reaction mixture was refluxed for 7 hours. The reaction was then cooled to ambient temperature and diluted with 200 ml of pentane, washed with 300 ml of cold aqueous sodium bicarbonate. The organic layer was then washed with cold 1.5 N hydrochloric acid. The resulting organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure and distilled under vacuum to get 18 gram of colourless 1-trimethyl silyloxy-1-cyclopentene. 1.26 gram of 1-trimethyl silyloxy-1-cyclopentene was mixed with 0.94 gram of 4-cyano benzaldehyde and 0.24 gram of sulphated zirconia in 40 ml of dichloromethane. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 40°C for 48 hours. The reaction mixture was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (5:1 V/V) as an eluent to get the pure 2-(4-cyano phenyl-1-hydroxy methylene) cyclopentanone. The yield obtained was 1.34 gram. Example 5 0.46 gram of 1-trimethyl silyloxy-1-cyclopentene was mixed with 0.54 gram of 4-nitro benzaldehyde and 0.12 gram of sulphated zirconia in 20 ml of dichloromethane. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 40°C for 40 hours. The reaction mixture was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (5:1 V/V) as an eluent to get the pure 2-(4-nitro phenyl,1-hydroxy methylene) cyclopentanone. The yield obtained was 1.34 gram. Example 6 0.95 gram of 1-trimethyl silyloxy-1-cyclopentene was mixed with 0.66 gram of 4-hydroxy benzaldehyde and 0.18 gram of sulphated zirconia in 3 0 ml of dichloromethane. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 35°C for 50 hours. The reaction mixture was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (5:1 V/V) as an eluent to get the pure 2-(4-hydroxy phenyl,1-hydroxy methylene) cyclopentanone. The yield obtained was 1.04 gram. Example 7 The 4-methyl-l-trimethyl silyloxy-1-cyclohexene is prepared by the known process and is described first. 32.6 gram of 1-trimethyl silyl chloride and 60.6 gram of triethylamine in 100 ml dry dimethyl formamide and 28.0 gram of 4-methyl cyclohexanone were stirred together in an inert atmosphere. The reaction mixture was refluxed for 5 hours. The reaction was then cooled to ambient temperature and diluted with 200 ml of pentane, washed with 300 ml of cold aqueous sodium bicarbonate. The organic layer was then washed with cold 1.5 N hydrochloric acid. The resulting organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure and distilled under vacuum to get 32 gram of colourless 4-methyl-1-trimethyl silyloxy-1-cyclohexene. 1.40 gram of 4-methyl-1-trimethyl silyloxy-1-cyclohexene was mixed with 0.94 gram of 4-cyano benzaldehyde and 0.24 gram of sulphated zirconia in 40 ml of dichloromethane. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 50°C for 36 hours. The reaction mixture was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (5:1 V/V) as an eluent to get the pure 2-(4-cyano phenyl-1-hydroxy methylene)-4-methyl cyclohexanone. The yield obtained was 1.56 gram. Example 8 0.72 gram of 4-methyl-l-trimethyl silyloxy-1-cyclohexene was mixed with 0.55 gram of 4-nitro benzaldehyde and 0.12 gram of sulphated zirconia in 3 0 ml of dichloromethane. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 4 0°C for 4 8 hours. The reaction mixture was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over anhydrous magnesium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (5:1 V/V) as an eluent to get the pure 2-(4-nitro phenyl-1-hydroxy methylene)-4-methyl cyclohexanone. The yield obtained was 0.79 gram. Example 9 0.72 gram of 4-methyl-l-trimethyl silyloxy-1-cyclohexene was mixed with 0.43 gram of 4-hydroxy benzaldehyde and 0.13 gram of sulphated zirconia in 3 0 ml of chloroform. A nitrogen atmosphere was maintained. The reactants were stirred at a temperature of 45°C for 52 hours. The reaction mixture was filtered to recover the solid catalyst. The filtrate was washed with distilled water, dried over anhydrous magnesium sulphate and the solvent was removed under reduced pressure. The resultant mass was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (5:1 V/V) as an eluent to get the pure 2-(4-hydroxy phenyl-1-hydroxy methylene)-4-methyl cyclohexanone. The yield obtained was 0.71 gram. The process of the present invention has following advantages : 1. The process is stereoselective in addition to regioselective. For the reaction at temperatures in the range of 30 to 40°C, preferential syn-selectivity is observed. 2. Sulphated zirconia acts as Lewis acid and hence the process offers the use. of a single catalyst. 3. The process can be carried out as a one pot synthesis for the preparation of monoadditive 2-(phenyl-1-hydroxy methylene) cycloalkanones. 4. Sulphated zirconia as the super-acid catalyst is used in small amounts compared to equimolar quantities of the Lewis acid used as the catalyst in known processes. 5. The super-acid catalyst can be recovered and used repeatedly after activation. The process is thus environmentally clean. 6. The product obtained as per the process of this invention meets the stringent purity requirements for use as mesogens in the synthesis of side chain liquid crystalline polymers for non-linear optical applications. 7. The process is amenable to scale up to meet the requirements which are usually small. We Claim: 1. An improved process for the preparation of 2- (aryl-1-hydroxy methylene) cycloalkanones which comprises; reacting silyl enol ether derivative of cycloalkanone of formula 2 with aromiatic aldehydes in presence of a solid super¬acid catalyst such as herein described, and a chlorinated solvent such as herein described, at ambient temperature in an inert atmosphere for a period ranging from 24 to 52 hours, filtering the reaction mixture to recover the super-acid catalyst, washing the filtrate with water, drying filtrate over a dehydrant, removing the chlorinated solvent under reduced pressure and recovering the product by column chromatography using an organic solvent as an eluent, to get the pure monabdditive 2-(aryl-l-hydroxy methylene) cycloalkanones of formula 1. 2. An improved process as claimed in claim 1 wherein, the silyl enol ether used is such as silyl enol ether of cyclopentene, cyclohexene and 4-methyl cyclohexene. 3. An improved process as claimed in claims 1 and 2 wherein, the aromatic aldehydes used is such as 4-cyano benzladehyde, 4-nitro benzaldehyde, 4-hydroxy benzaldehyde. 4. An improved process as claimed in claims 1 to 3 wherein, the inert atmosphere may be maintained by using inert gas like nitrogen or argon. 5. An improved process as claimed in claims 1 to 4 wherien, the aliphatic hlorinated solvent used is such as tetrachloro ethane. An improved process as claimed in claims 1 to 5 wherein, the solid super-acid catalyst chosen is sulphated zirconia. An improved process as claimed in claims 1 to 6 wherein, the dehydrant used to dry the washed product is such as sodium sulphate, magnesium sulphate and calcium chloride. An improved process for the preparation of 2-(aryl-l- hydroxy methylene) cycloalkanones as substantially described hereinbefore with reference to the examples.

Documents:

428-del-1997-abstract.pdf

428-del-1997-claims.pdf

428-del-1997-complete specification (granted).pdf

428-del-1997-correspondence-others.pdf

428-del-1997-correspondence-po.pdf

428-del-1997-description (complete).pdf

428-del-1997-drawings.pdf

428-del-1997-form-1.pdf

428-del-1997-form-19.pdf

428-del-1997-form-2.pdf