Patent GB-507565-A (GB)
Title: Process for the preparation of amidine derivatives
Filed: 1937-12-10
Abstract: 507,565. Amidines. MAY & BAKER, Ltd., EWINS, A. J., BARBER, H. J., NEWBERY, G., ASHLEY, J. N., and SELF, A. D. H. Dec. 10, 1937. Nos. 34288/37, 1074/38, 1075/38, 3133/38, 5606/38, 7376/38, and 11559/38. [Class 2 (iii)] Diamidines are prepared from dicyano compounds of the formula NCRXRCN, where each R represents a benzene nucleus and X is a simple linkage or a group (CH2)n, where n is 1-12 and one or more of the CH2 groups may be replaced by oxygen or sulphur or by a group NH. The method of preparing the diamidines consists in treating the dicyano compounds in solution in an anhydrous aliphatic alcohol with dry hydrogen chloride or hydrogen bromide, optionally in the presence of an additional solvent, whereby the corresponding iminoether hydrohalides are obtained ; the latter are then converted into amidines by reaction with ammonia, optionally in alcoholic solution. Examples are given of the manufacture of diamidines from (1) 4 : 41-dicyanodiphenylmethane, prepared from 4 : 4<1>-diaminodiphenylmethane by the Sandmeyer reaction ; (2) 4 : 4- dicyanodiphenyl, prepared from benzidine by the Sandmeyer reaction; (3) 4 : 4<1>-dicyanodiphenyl sulphide, prepared from 4 : 4<1>-diaminodiphenyl sulphide; (4) 4 : 4<1>-dicyanodiphenyl ether, prepared from 4 : 4<1>-diaminodiphenyl ether; (5) 4 : 4<1>-dicyanobenzyl aniline, prepared by condensing p-cyanobenzyl chloride with p-aminobenzonitrile; (6) 4 : 4<1>-dicyanophenylbenzyl ether, prepared from p-cyanobenzyl chloride and p-cyanophenol; (7) 4 : 4<1>-dicyanodibenzyl, prepared by dehydrating the oxime of dibenzyl-4 : 4<1>-dialdehyde; (8) 4 : 4<1>-dicyanoalpha, #-diphenoxyethane, prepared by condensing p-hydroxybenzonitrile with ethylene dibromide; (9) 4 : 4<1>-dicyano-alpha, gamma-diphenoxypropane, prepared from p-hydroxybenzonitrile and alpha, gamma-dibromopropane; (10) 4 : 4<1>-dicyano-#-phenoxyethylaniline, prepared by heating p-aminobenzonitrile with # - (p - cyanophenoxy)ethyl bromide, which is itself prepared from phydroxybenzonitrile and ethylene dibromide; (11) 4: 4<1>-dicyanodibenzyl sulphide; (12) 4 : 4'- dicyanodibenzylamine; (13) 4 : 41-dicyanodibenzyl ether, prepared by condensing 4-cyanobenzyl chloride with 4-cyanobenzyl alcohol, or from dibenzyl ether 4 : 4<1>-dicarboxylic acid by known methods; (14) p, p<1>-dicyano-1 : 5-diphenoxypentane, prepared from p-hydroxybenzonitrile and pentamethylene dibromide, and (15) p, p<1>-dicyano-1 : 10-diphenoxydecane, prepared from p-hydroxybenzonitrile and 1 : 10- dibromodecane. The products are of therapeutic value. The first Provisional Specification refers to the manufacture of amidine derivatives of di- and tri-aryl-methanes, and states that these may be prepared from the corresponding cyano compounds (a) by converting the cyano compounds into imino-ethers, and treating the latter with ammonia or an alkyl- or aryl-amine, or (b) by converting the cyano compounds into carboxylic acids, and treating the amides of the acids with phosphorus pentachloride to yield the corresponding imide chlorides, which are then condensed with ammonia or an alkyl- or aryl-amine. The second Provisional Specificat,ion refers to the manufacture of diamidines of diaryl and substituted, diaryl compounds, and indicates that these may be prepared from the corresponding cyano compounds by the methods set out above or by treating the corresponding carboxylic acid amides with phosphorus pentasulphide to form the thioamides, which are then treated with ammonia or an amine. The third Provisional Specification refers to the manufacture of diamidine derivatives of diaryl oxides, sulphides, sulphoxides or sulphones, and indicates that these may be prepared from the corresponding cyano compounds by any of the methods set out above. The fourth Provisional Specification refers to the manufacture in similar manner of mono- or di-amidine derivatives of compounds of the formula RNHR<1>, where R and R<1> are aryl or aralkyl groups, which may be substituted ; the amidine group or groups may be attached directly to a nucleus or to the side chain of an aralkyl -or alkyl-substituted aryl group. It includes an example in which 4-cyano-4'-carboxyamidodipheny lamine is converted into 4- amidino-4<1>-carboxyamidodiphenylamine by way of the imino-ether. The fifth Provisional Specification refers to the manufacture, by the methods described above, of diamidine derivatives of aryl-aralkyl or diaralkyl ethers, sulphides, sulphoxides or sulphones. The sixth Provisional Specification refers to the manufacture, in similar manner, of mono- or diamidine derivatives of compounds of the formula R(CH2)nR<1>, in which R and R<1> are identical or different aryl groups, which may contain substituents such as methyl, hydroxy or amino groups ; the specified products include #-amidino- and #, #<1>-diamidinodimethyldibenzyl.