Title of Invention

"AN IMPROVED PROCESS FOR THE PREPARATION OF MONOCODENSED BENZYLIDINE CYCLOALKANONES"

Abstract

This invention relates to an improved process for the preparation of monocondensed benzylidene cycloalkanones. This compounds are useful for the preparation of mesogens that would find applications in the synthesis of side chain liquid crystalline polymers. The compounds offers high regio-selectivity. The known processes are i) two step process, ii) catalyst is hygroscopic and hazardous iii) catalyst cannot be recovered. These drawbacks have been removed in the present invention.

Full Text

This invention relates to an improved process for the preparation of monocondensed benzylidene cycloalkanones. More particularly it relates to the preparation of the monocondensed benzylidene cycloalkanones 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 pclymers. In particular, this invention describes a process for the preparation of monocondensed benzylidene cycloalkanones, that offers high regio-selectivity. Mesogens are moieties which form part of the polymeric structure ir. liquid crystalline polymers. If the mesogens form part of the backbone of the polymer, then the polymer is known as main chain liquid crystalline polymer and if it is in the form of pendant grcups 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 fcr the synthesis of side chain liquid crystalline polymers that cculd be used for non-linear optical applications. The hitherto known processes for the preparation of benzylidene 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 condensed product and bis condensed products are obtained (J.Am.Chem.Soc. (1959), 628 and references cited therein). Another known process that offers regio selectivity to give monocondensed product involves the reaction of cyclohexene silyl enoi ether with aroiaatic aldehydes in the presence of titanium tetrachloride. This reaction offers exclusively monocondensed product. The known process however suffers from the following disadvantages : (J.Am.Chem.Soc. (1974), 96, 7503). 1. The reaction is two step process - the first one involves the formation of an intermediate aldol using a Lewis acid which is isolated followed by the second step of dehydration with the use of a Bronsted acid. Thus the process needs the use of two catalysts. 2. Equimolar amount of titanium tetrachloride needs to be added, though the function of titanium tetrachloride is that of a Lewis acid catalyst. 3. The catalyst, titanium tetrachloride is hygroscopic and hazardous to handle. 4. The catalyst cannot be recovered at the end of the reaction giving rise to disposal and environmental hazards. o 5. The reaction is carried out at -78 C. It is difficult to maintain this reaction condition in the laboratory. The main object of the present invention is to provide an Improved process for the preparation of monocondensed benzylidene cycloalkanones that eliminates the above mentioned disadvantages such as elimination of a second catalyst in the hitherto known process. Another object of the present invention is to provide a prcosess 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 monocondensed benzylidene cycloalkanones of formula 1 shown in drawing accompanying with the specification which comprises : reacting silyl enol ether derivative of cycloalkanone of formula 2 of the drawing with aromatic aldehydes as herein described in the ratio 1.1:1 to 1.7 :1 (w/w) in an inert atmosphere in the presence of a solid super acid catalyst such as sulphated zirconia at a temperature in the range of 110 to 140 deg.C for a period ranging from 24 to 52 hrs, dispersing the reaction mixture in a aliphatic chlorinated solvent as herein described, filtering the reaction mixture to recover the super acid catalyst followed by washing the filtrate first with aliphatic chlorinated solvent and then with water, drying the filtrate over a conventional dehydrant as herein described, removing the chlorinated solvent under reduced pressure and purifying the product by column chromatography using an organic solvent system to get the pure monocondensed benzylidene cycloalkanones of formula 1 of the drawing accompanying this specification. In one of the embodiment of the present invention the silyl enol used may be such as silyl enol ether of cyclohexene, cyclopentene and 4-methyl cyclohexene. In another embodiment the aromatic aldehydes used may be such as 4-cyano benzaldehyde, 4-nitro benzaldehyde, 4-hydroxy benzaldehyde. According to 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, tetrachloro ethane. According to yet another feature of the invention, the solid super-acid catalyst used may be such as sulphated zirconia. According to yet another feature of the invention, the dehydrant used to dry the washed product may be such as sodium sulphate, magnesium sulphate. According to yet another feature of the invention, the eluent mixture used for separation in chromatography may be such as petroleum ether : Acetone in the range of increasing polarity. 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 prepared by the known process 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 200 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 under nitrogen atmosphere. The reactants were refluxed at a temperature of 125°C for 36 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of dichloromethane and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture {6:1 V/V) as the eluent to get the pure 2-(4-cyano benzylidene) cyclohexanone. The yield obtained was 1.3 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 zirconia. A nitrogen atmosphere was maintained. The reactants were re fluxed at a temperature of 13 5°C for 4 0 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of chloroform and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (6:1 V/V) as the eluent to get the pure 2-(4-nitro benzylidene) cyclohexanone. The yield obtained was 0.73 gram. Example 3 0.68 gram of 1-trimethyl silyloxy-1-cyclohexene was mixed with 0.44 gram of 4 -hydroxy benzaldehyde and 0.13 gram of sulphated zirconia. An argon atmosphere was maintained. The reactants were refluxed at a temperature of 14 0°C for 42 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of dichloroethane and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (6:1 V/V) as the eluent to get the pure 2- (4-hydroxy benzylidene) cyclohexanone. The yield obtained was 0.62 gram. Example 4 The 1-trimethyl silyloxy-1-cyclopentene prepared by the known process 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 l-trimethyl silyloxy-1-cyclopentene. 1.26 gram of l-trimethyl silyloxy-1-cyclopentene was mixed with 0.95 gram of 4-cyano benzaldehyde and 0.25 gram of sulphated zirconia. An argon atmosphere was maintained. The reactants were refluxed at a temperature of 110°C for 4 8 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of dichloromethane and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (6:1 V/V) as the eluent to get the pure 2- (4-cyano benzylidene) cyclopentanone. The yield obtained was 1.28 gram. Example 5 0.65 gram of l-trimethyl silyloxy-1-cyclopentene was mixed with 0.55 gram of 4-nitro benzaldehyde and 0.125 gram of sulphated zirconia. A nitrogen atmosphere was maintained. The reactants were refluxed at a temperature of 125°C for 42 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of chloroform and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (6:1 V/V) as the eluent to get the pure 2-(4-nitro benzylidene) cyclopentanone. The yield obtained was 0.70 gram. Example 6 0.63 gram of 1-trimethyl silyloxy-1-cyclopentene was mixed with 0-45 gram of 4-hydroxy benzaldehyde and 0.13 gram of sulphated zirconia. A nitrogen atmosphere was maintained. The reactants were refluxed at a temperature of 130°C for 52 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of dichloromethane and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (6:1 V/V) as the eluent to get the pure 2- {4-hydroxy benzylidene) cyclopentanone. The yield obtained was 0.63 gram. Example 7 The 4-methyl-1-trimethyl silyloxy-1-cyclohexene prepared by the known process is described first. 32.6 gram of 1-trimethyl silyl chloride and 60.6 gram of triethylamine in 100 ml dry dimethyl f ormamide 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. 1.24 gram of 4-methyl-1-trimethyl silyloxy-1-cyclohexene was mixed with 0.94 gram of 4-cyano benzaldehyde and 0.25 gram of sulphated zirconia. A nitrogen atmosphere was maintained. The reactants were refluxed at a temperature of 140°C for 40 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of dichloromethane and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (6:1 V/V) as the eluent to get the pure 2- (4-cyano benzylidene)-4-methyl cyclohexanone. The yield obtained was 1.4 0 gram. Example 8 0.72 gram of 4-methyl-1-trimethyl silyloxy-1-cyclohexene was mixed with 0.54 gram of 4-nitro benzaldehyde and 0.12 gram of sulphated zirconia. An argon atmosphere was maintained. The reactants were refluxed at a temperature of 130°C for 48 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of chloroform and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture {6:1 V/V) as the eluent to get the pure 2-(4-nitro benzylidene)-4-methyl cyclohexanone. The yield obtained was 1.4 0 gram. Example 9 1.08 gram of 4-methyl-1-trimethyl silyloxy-1-cyclohexene was mixed with 0.65 gram of 4-hydroxy benzaldehyde and 0.18 gram of sulphated zirconia. A nitrogen atmosphere was maintained. The reactants were refluxed at a temperature of 140°C for 40 hours. The reaction mixture was cooled to ambient temperature and dispersed in 50 ml of dichloromethane and 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 mixture was then chromatographed through a silica gel column using a petroleum ether : acetone mixture (6:1 V/V) as the eluent to get the pure 2-(4-hydroxy benzylidene)-4-methyl cyclohexanone. The yield obtained was 1.05 gram. The process of the present invention has following advantages : 1. The process is steroselective in addition to regio selective. In the reaction at temperatures in the range of 110 to 140°C/ preferential syn-selectivity is observed. 2. Sulphated zirconia acts both as Lewis acid and Bronsted 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 monocondensed benzylidene cyclohexanones without the separation of the aldol formed first. 4. Sulphated zirconia as the super acid catalyst is used in small amounts compared to eguimolar 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 a mesogen 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 monocondensed benzylidene cycloalkanones of formula 1 shown in drawing accompanying with the specification which comprises : reacting silyl enol ether derivative of cycloalkanone of formula 2 of the drawing with aromatic aldehydes as herein described in the ratio 1.1:1 to 1.7 :1 (w/w) in an inert atmosphere in the presence of a solid super acid catalyst such as sulphated zirconia at a temperature in the range of 110 to 140 deg.C for a period ranging from 24 to 52 hrs, dispersing the reaction mixture in a aliphatic chlorinated solvent as herein described, filtering the reaction mixture to recover the super acid catalyst followed by washing the filtrate first with aliphatic chlorinated solvent and then with water, drying the filtrate over a conventional dehydrant as herein described, removing the chlorinated solvent under reduced pressure and purifying the product by column chromatography using an organic solvent system to get the pure monocondensed benzylidene cycloalkanones of formula 1 of the drawing accompanying this specification. 2. An improved process as claimed in claim 1, wherein the silyl enol ether used is such as of cyclohexanone,cyclopentanone, 4-methyl cyclohexanone. 3. An improved process as claimed in claims 1 and 2, wherein the aromatic aldehydes used is such as 4-cyano benzaldehyde, 4-nitro benzaldehyde, 4-hydroxy benzaldehyde. 4. An improved process as claimed in claims 1-3, wherein the inert atmosphere may be maintained by using inert gas like nitrogen or argon. 5. An improved process as claimed in claims 1-4, wherein the aliphatic chlorinated solvent used is such as dichloromthane, chloroform, carbon tetrachloride, tetrachloro ethane. 6. An improved process as claimed in claims 1-5, wherein the dehydrant used to dry the washed product is such as sodium sulphate, magnesium sulphate and calcium chloride. 7. An improved process as claimed in claims 1-6, wherein the eluent mixture used for separation in chromatography is petroleum ether : acetone in the ratio of increasing polarity. 8. An improved process for the preparation of monocondensed benzylidene cycloalkanones as substantially described hereinbefore with reference to the examples.

Documents:

434-del-1997-abstract.pdf

434-del-1997-claims.pdf

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

434-del-1997-correspondence-others.pdf

434-del-1997-correspondence-po.pdf

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

434-del-1997-drawings.pdf

434-del-1997-form-1.pdf

434-del-1997-form-19.pdf

434-del-1997-form-2.pdf