Patent GB-1367691-A (GB)
Title: Process for the manufacture of benzene derivatives
IPC: C07D225/06
Filed: 1971-08-18
Abstract: 1367691 Benzene derivatives F HOFFMANNLA ROCHE & CO AG :18 Aug 1971 [19 Aug 1970] 38756/71 Heading C2C Benzene derivatives are prepared by chloromethylating, by reaction with formaldehyde and hydrogen chloride, a protected amine of the general formula wherein each of R 2  and R 3  is a C 1-7  alkyl or C 1-7  alkoxy group or R 2  and R 3  together form a methylenedioxy group, R 4  is a hydrogen atom, a C 1-7  alkyl or carboxy group, or an aryl group optionally substituted by a halogen atom or C 1-7  alkyl, nitro or trifluoromethyl group, X is a protecting group and n is 1 or 2, optionally converting the chloromethyl group in the product of the general formula to a cyanomethyl group, by treatment with an alkali metal cyanide, converting the resulting nitrile of the general formula  to an ester of the general formula by a method known per se, hydrolysing the ester, splitting off the protecting group X from the resulting acid by a method known per se, optionally benzylating or C 1-7  alkylating the resulting amine of the general formula intramolecularly condensing the resulting substituted amine of the general formula wherein R 10 <SP>1</SP> is a benzyl Or C 1-7  alkyl group, or the amine from which it is obtained, optionally reducing the resulting lactam of the general formula  wherein R 10  is a hydrogen atom or benzyl or C 1-7  alkyl group, optionally debenzylating by catalytic hydrogenation a resulting heterocyclic amine of the general formula or a lactam of the immediately preceding general formula, optionally introducing by a method known per se a substituent R 6  into an obtained lactam or heterocyclic amine in which R 10  is a hydrogen atom to give a compound of the general formula wherein B is -CH 2 - or -CO- and R 5  is a hydrogen atom or a C 1-7  alkyl, hydroxy-C 1-7  alkyl, C 2-8  alkanoyl, halo-C 2-8  alkanoyl, amino- C 2-8  alkanoyl, mono- or di-C 1-7  alkyl-amino- C 2-8  alkanoyl, C 2-7  alkenyl, amino-C 1-7  alkyl, mono- or di-C 1-7  alkyl-amino-C 1-7  alkyl, carboxy-C 1-7  alkyl, C 2-8  carbalkoxy-C 1-7  alkyl, di- C 1-7  alkyl-carbamoyl-C 1-7  alkyl, benzoyl-C 1-7  alkyl, halobenzoyl-C 1-7  alkyl or -COCH 2 R 6  group (in which R 6  is a phenyl group, optionally substituted by a halogen atom or C 1-7  alkyl, nitro or trifluoromethyl group), optionally halogenating this compound in the benzene ring and optionally converting the product of the general formula  wherein R 1  is a hydrogen or halogen atom, into an acid addition salt thereof; or catalytically hydrogenating 4,5-methylenedioxy-1,2-benzenediacetonitrile in the presence of ammonia and Raney nickel, optionally introducing a substituent R 5  or R 10 <SP>1</SP> into the resulting 2,3,4,5- tetrahydro - 7,8 - methylenedioxy - 1H - 3- benzazepine, and optionally converting the product to an acid addition salt thereof. N - Acetyl - α - methylhomopiperonylamine is prepared by reacting α-methylhomopiperonylamine with acetic anhydride. 4,5 - Methylenedioxy - 1,2 - benzene - diacetonitrile is prepared by treating 4,5-methylenedioxy-1,2-bis-(chloromethyl)benzene with NaCN Protected amines of the first general formula above wherein X is a phthaloyl group are prepared by reaction of the free amine with phthalic anhydride.