Patent GB-983661-A (GB)
Title: Benzyloxyamines and compositions containing them
Filed: 1962-01-17
Abstract: The invention comprises (1) compounds of the formula <FORM:0983661/C2/1> (wherein X is hydrogen, one or two alkyl groups each of at most 3 carbon atoms or halogen, Y is hydrogen, -COR, -CO.OR, -CO.NH2 or -CO.NHCO.R, and Z is hydrogen or aralkyl; or wherein X is alkoxy, Y is hydrogen, -CO.R or -CO.OR and Z is aralkyl; or wherein X is trifluoromethyl, Y is -CO.R or -CO.OR and Z is hydrogen or aralkyl; R being an alkyl, alkoxyalkyl or aryl group; Z, when aralkyl, being unsubstituted or substituted by one or two alkyl groups, an alkoxy or trifluoromethyl group or a halogen atom; the aralkyl groups containing 7 to 12 carbon atoms, the group R when alkyl, containing 1 to 20 carbon atoms and, when aryl, 6 to 10 carbon atoms; with the provisos that (1) when X is a halogen atom and Z is hydrogen, then Y cannot be hydrogen, -CO.OC2H5 or -CO.NH2; (2) when X is a halogen atom and Z is aralkyl then Y cannot be hydrogen; and (3) when X is hydrogen and Z is hydrogen or a benzyl group then Y cannot be hydrogen, -CO.NH2, -CO.OC2H5, -CO.CH3 or -CO.C6H5) and their acid-addition salts when Y and Z are hydrogen atoms or Z is an aralkyl group; and their preparation by reacting a hydroxylamine derivative NY1Z1OH (wherein Y1 and Z1 are Y and Z or hydrolysable protecting groups) with one or two moles of a compound of the formula <FORM:0983661/C2/2> (wherein K is a halogen atom or the residue of a sulphonic acid or ester) and then, if desired, when the protecting group is -CO.R or -CO.Or, hydrolysing to form a product in which Z is hydrogen, or when the protecting group is -CO.OR, treating with ammonia to form a product in which Y is -CO.NH2, and hydrolysing all other protecting groups to form a product in which Z is hydrogen; and then, if desired, when Y and Z in the product are hydrogen atoms or Z is an aralkyl group, acylating to give a product in which Y is -CO.R, or reacting with cyanic acid to give a product in which Y is -CO.NH2, or reacting with a haloformate Hal.CO.OR, a carbonate RO.CO.OR or with phosgene and then an alcohol ROH or ammonia to give a product in which Y is -CONH2 or -CO.OR.  The hydroxylamine derivative used as starting material may, inter alia, have the formula HO.NH.CO.R or HO.NH.CO.OR or it may have the formula <FORM:0983661/C2/3> wherein K is an organic residue to form a cyclic imide, or it may be an aldoxime or ketoxime, or it may be a metal salt of hydroxylamine disulphonic acid.  One mole each of different starting materials of the second general formula above may be used to give products in which X-C6H4-CH2- and Z are different.  Extensive examples and lists of products are provided.ALSO:Compositions for reducing blood cholesterol in warm-blooded animals comprise one or more benzyloxyamines of the formula <FORM:0983661/A5-A6/1> (wherein X is hydrogen, one or two alkyl groups each of at most 3 carbon atoms or halogen; Y is hydrogen, -CO.R, -CO.OR, -CO.NH2 or -CO.NHCO.R; and Z is hydrogen or aralkyl; or wherein X is alkoxy; Y is hydrogen, -CO.R or -CO.OR; and Z is aralkyl; or wherein X is trifluoromethyl; Y is -CO.R or -CO.OR, and Z is hydrogen or aralkyl; R being an alkyl, alkoxyalkyl or aryl group; and Z, when aralkyl being unsubstituted or substituted by one or two alkyl groups, an alkoxy or trifluoromethyl group, or a halogen atom; the aralkyl groups containing 7 to 12 carbon atoms, and the group R, when alkyl, containing 1 to 20 carbon atoms and when aryl, 6 to 10 carbon atoms) or their acid-addition salts when Y and Z are hydrogen atoms or Z is an aralkyl group, and suitable carriers therefor. They may take the form of tablets or capsules.  Specified ingredients are N-(p-methylbenzyl)-N - (p - methylbenzyloxy) - amine or its hydrochloride, N - benzyl - N - benzyloxy - urea, p - chlorobenzylcarbethoxyhydroxamate, m-methylbenzyl N - m - methylbenzylcarbethoxyhydroxamate, benzyl N - benzylcarbethoxyhydroxamate, N - benzyl - N - benzyloxyamine or its hydrochloride, benzyl carbethoxyhydroxamate, m - methylbenzylcarbethoxyhydroxamate, p - chlorobenzyl N - p - chlorobenzylcarbethoxyhydroxamate, p - methylbenzyl N-p - methylbenzylcarbethoxyhydroxamate, benzyl N - benzylcarbophenoxyhydroxamate, benzyl N - benzylbenzhydroxamate, benzyl N - benzylacethydroxamate, benzyl N - benzylisobutyrhydroxamate, N - (gamma - phenylpropyl) - N - benzyloxyamine hydrochloride, N - benzyl - N - (m - methylbenzyloxy) - amine, p - chlorobenzyloxyamine, p - methoxybenzyl N - p - methoxybenzylcarbethoxyhydroxamate and m - trifluoromethylbenzyl N - m - trifluoromethylbenzyl carbethoxyhydroxamate.