Patent GB-548349-A (GB)
Title: Improvements in and relating to the synthesis of heterocyclic compounds
IPC: C07D219/04
Filed: 1941-03-04
Abstract: 548,349. Heterocyclic compounds, PETROW, V., and IMPERIAL CHEMICAL INDUSTRIES, Ltd. March 4, 1941, No. 2922. [Class 2 (iii)] Heterocyclic compounds are prepared by reacting a formyl ketone of the general formula R.CH 2 .CO CH (CHO) R<SP>1</SP> with one molecule of a primary aromatic amine and then reacting the resulting anil with another molecule of the amine with ring-closure and the elimination of one molecular proportion of the amine. In the above formula Rand R<SP>1</SP> may represent aliphatic groups or hydrogen or many together with CH 2 .CO.CH 2  form a cyclohexanone ring. The aromatic amine must have at least one ortho position unsubstituted. The first condensation is preferably effected in aqueous or alcoholic solution, and the second condensation is preferably effected by heating in an anhydrous solvent in the presence of a dehydrating agent such as fused zinc chloride. In an alternative procedure the entire reaction may be carried out in one stage. Formyl ketones mentioned include formyl acetone, 2- formyl-3-butanone, 2-formylcyclohexanone, 2- formyl-4-methyl-cyclohexanone, 2-formyl-5- methyl - cyclohexanone. Primary amines mentioned include aniline, 1-naphthylamine, 2- naphthylamine, o-, m-, or p-toluidine, pxylidine, o-, m-, or p-chloraniline, o- or panisidine, o-, m-, or pbromoaniline, p-iodoaniline, p-phenylaniline, macetylaniline, m- or p-carbethoxyaniline, p-hydroxyaniline, p-nitroaniline or p-aminodiphenylamine. In examples (1) formylacetone is reacted with aniline hydrochloride in aqueous solution to give phenyliminomethylacetone which is further reacted with aniline hydrochloride in absolute. alcohol in the presence of zinc chloride to give quinoline which is isolated as its picrate. (2) Aniline is reacted with 2-formyl-3 butanone to give 2 - (phenyliminomethyl) - 3 - butanone which is further treated with aniline to form 2:3-dimethyl-quinoline. (3) 2-formyl-3- butanone is reacted with 1-naphthylamine to give 2-(1<SP>1</SP>-naphthyliminomethyl)-3-butanone which on further treatment with 1-naphthylamine gives 2:3-dimethyl-7:8-benzoquinoline. (4) 2-formylcyclohexanone is reacted with 2- naphthylamine to give 2-(2<SP>1</SP>-naphthyliminomethyl) cyclohexanone which on further treatment with 2-naphthylamine gives 1:2:3:4- tetrahydro-6:7-benzacridine. (5) 2-formylcyclohexanone is reacted with p-anisidine to give 2 - (p - - methoxyphenyliminomethyl) - cyclohexanone, which on further treatment with p-anisidine yields 7-methoxy-1:2:3:4- tetrahydroacridine. (6) 2-formylcyclohexanone is reacted with two molecules of o-toluidine in one step to produce 9-methyl-1:2:3:4-tetrahydroacridine. (7) 2- formylcyclohexanone is reacted with o-chloraniline in two stages as in example (1) to give 9-chloro-1:2:3:4-tetrahydroacridine. (8) 2-formyl cyclohexanone is reacted with molten p-carbethoxyaniline to give 2- (p-carbethoxyphenyliminomethyl)-cyclohexanone which is treated with additional pcarbethoxyaniline hydrochloride in absolute alcohol solution with zinc chloride to give 7- carbethoxy-1:2:3:4-tetrahydroacridine. (9) 2- formylcyclohexanone is reacted with p-aminodiphenylamine to give 2-(p-phenylaminophenyliminomethyl)-cyclohexanone, which on further treatment with p-amino-diphenylamine gives 7-phenylamino-1:2:3:4-tetrahydroacridine