Patent GB-1249383-A (GB)
Title: Benzylthio-benzylsulphinyl- and benzylsulfonylbenzoic acid derivatives
IPC: A61K31/18
Filed: 1969-02-18
Abstract: 1,249,383. Benzylthio-, benzylsulphinyl-, benzylsulphonyl-benzoic acids and derivatives thereof. PFIZER Inc. 18 Feb., 1969 [22 April, 1968; 3 Oct., 1968], No. 8843/69. Heading C2C. Novel compounds I to XIII (including salts, amides and C 1-6  alkyl esters thereof) wherein R signifies CH 3 , CF 3  or NO 2 , X signifies H, CH 3 , mono- or di-CH 3 O, NO 2 , Cl, Br, F, I, CF 3  or CF 3 SO 2 , R<SP>1</SP> signifies Cl, Br, F, OCF 3 , CH 3 O, CF 3 SO 2 , (CH 3 OCH 2 CH 2 ) 2 NSO 2  or (R<SP>2</SP>R<SP>3</SP>)NSO 2  wherein R<SP>2</SP> and R<SP>3</SP> signify H, C 1-16  alkyl, aryl and arylalkyl up to 10 carbons or taken together signify polymethylene or alkylpolymethylene containing up to 15 carbons provided that R<SP>2</SP> and R<SP>3</SP> are not simultaneously H, R<SP>4</SP> signifies H, CH 3 , CF 3 , NO 2 , Cl, Br, F, CH 3 O, OCF 3 , CF 3 SO 2 , (CH 3 OCH 2 CH 2 ) 2  NSO 2  or (R<SP>2</SP>R<SP>3</SP>)NSO 2  and R<SP>5</SP> signifies -CH 2 -α (or -#-)-naphthyl, -CH 2 -α (or -#-) -thienyl, -CR<SP>6</SP>R<SP>7</SP>.(CH 2 ) n .C 6 H 4 .X or -CR<SP>6</SP>R<SP>7</SP>.CH: CH.C 6 H 4 .X wherein n is 0, 1, 2 or 3 and R<SP>6</SP> and R<SP>7</SP> signify H, C 1-6  alkyl or -C 6 H 4 .X provided that R<SP>6</SP> and R<SP>7</SP> are not simultaneously H when n is 0, are obtained: (a) by reacting the appropriate X-substituted benzyl halide (or R<SP>5</SP>.Halogen) with the appropriate R<SP>4</SP>-substituted-mercapto-benzoic acid (prepared by fission of the corresponding disulphide) and optionally oxidizing the product so obtained; (b) by reacting the appropriate X-substituted-benzyl mercaptan (or R<SP>5</SP>.SH) with the appropriate R<SP>4</SP> - substituted - halogen - substituted - benzoic acid, or corresponding nitrile in which case a subsequent hydrolysis step is included, and optionally oxidizing the product so obtained; or (c) by reacting the appropriate X-substitutedbenzyl halide with the appropriate R<SP>4</SP>-substituted-sulphino-sbustituted benzoic acid and hydrolysing the product so obtained. 3 - Sulphino - 5 - trifluoromethylbenzoic acid, obtained by diazotization of 3-amino-5-trio fluoromethylbenzoic acid utilizing sulphur dioxide in the presence of copper, is converted to benzyl 3 - benzylsulphonyl - 5 - trifluoromethylbenzoate by refluxing with benzyl chloride. 2 - Mercapto 4 - trifluoromethylbenzoic acid is prepared by hydrolysing 2-carboxy-5-trifluoromethylphenyl ethyl dithiocarbonate (obtained by diazotization of 2-amino-4-trifluoromethylbenzoic acid utilizing potassium ethyl xanthate). 2 - Benzylthio - 5 - trifluoromethylbenzonitrile is prepared by the interaction of 4-chloro-3- cyanobenzotrifluoride and benzylmercaptan. 2 - Chloro - 5 - chlorosulphonylbenzoic acid, obtained by the interaction of o-chlorobenzoic acid and chlorosulphonic acid, is converted to the corresponding 2 - chloro - 5 - (R<SP>2</SP>R<SP>3</SP>)NSO 2 - benzoic acid by reaction with an amine (R<SP>2</SP>R<SP>3</SP>)NH. 3 - Iodo - 5 - trifluoromethylbenzoic acid is obtained by diazotization of 3-amino-5-trifluoromethylbenzoic acid utilizing potassium iodide in the presence of copper; other 3- iodo - 5 - R<SP>4</SP> - substituted - benzoic acids are similarly obtained. 2,2<SP>1</SP> - Dicarboxy - di - 4 - tolyl disulphide is prepared by treating 5-methylanthranilic acid with sodium polysulphide. Pharmaceutical preparations effective as hypolipemic agents and suitable for the treatment of atherosclerosis and related cardiovascular diseases contain as active ingredient compounds I to XV; administration is orally or parenterally.