Patent GB-767148-A (GB)
Title: New acetanilide derivatives and the manufacture thereof
Inventor: BRISTOW NORMAN WILLIAM
IPC: C07C233/00
Filed: 1954-07-22
Abstract: The invention comprises compounds of the formula <FORM:0767148/IV(b)/1> in which R is an alkyl or aralkyl radical, and in which the phenyl radical X is substituted by one or more groups (which may be the same or different) selected from nitro, hydroxy, alkoxy, aralkoxy, aryloxy, carboxyalkoxy, alkenoxy, alkylenedioxy, and -NR1R2 groups wherein R1 and R2 may be the same or different and represent hydrogen, or alkyl groups; also a process for their preparation by reacting the corresponding N-alkyl or aralkylamino compound (except those substituted by primary or secondary amino groups) with dichloracetyl chloride in the presence of an acid-binding agent, which may be sodium acetate or an excess of the amine reactant.  The compounds wherein X contains one or more nitrogroups may also be produced by direct nitration and the corresponding primary amino compounds then obtained by reduction, preferably with stannous chloride.  The alkoxy and aralkoxy compounds may be prepared from the corresponding hydroxy compounds by alkylation or aralkylation. In examples: dichloroacetyl chloride in benzene is added slowly to a cooled mixture of p-methylaminophenol sulphate, sodium bisulphite and sodium acetate trihydrate in benzene, when dichloroacet-4-hydroxy-N-methylanilide separates; other dichloracetanilides similarly prepared are 2-hydroxy - N - methyl-, 2 - hydroxy - N - ethyl-, 3 - hydroxy - N - methyl-, 4 - hydroxy - N - ethyl-, 4 - butoxy - N - methyl-, 4 - methoxy - N - methyl-, 4 - methoxy - N - ethyl-, 4-ethoxy-N - methyl-, 4 - hydroxy - N - propyl-, 4 - hydroxy - N - benzyl-, 3 - methoxy - N - methyl-, 4 - methoxy - N - propyl-, 4 - n - propoxy - N - methyl-, 4 - isopropoxy - N - methyl-, 4 - allyl - oxy - N - methyl-, 4 - phenoxy - N - methyl-, 2-methoxy - N - methyl-, 3,4 - dimethoxy - N - methyl-, 2 - n - butoxy - N - methyl-, 3 - nitro-N - methyl-, 4 - nitro - N - methyl-, and 4-dimethylamino - N - methyl- and using methyl propyl ketone as solvent 3,4-dihydroxy-N-methyl-, and 3,5 - dihydroxy - N - ethyl-. Phloroglucinol and aqueous methylamine are reacted in the absence of air, and then treated with dichloroacetyl chloride in methyl propyl ketone, giving dichloracet-3,5-dihydroxy-N-methylanilide; dichloracet - 4 - methoxy - N - methyl-, 4 - butoxy - N - methyl-, 3 - butoxy-N - methyl- and 4 - benzyloxy - N - methyl-anilides and 4-(dichloro - N - methylacetamido)-phenoxyacetic acid are prepared from the corresponding hydroxy compounds by etherification using potassium carbonate and the appropriate alkyl or aralkyl halide or ethyl bromoacetate.  4-Methylaminoveratrole, acetic acid and aqueous HBr are refluxed together, the solvent distilled off and the residue treated with dichloracetyl chloride and sodium acetate in aqueous benzene, giving dichloracet-3-hydroxy-4 -methoxy-N-methylanilide; 4-nitromethylenedioxybenzene is hydrogenated over palladium charcoal and the resulting 4-aminomethylenedioxy benzene formylated to give 3,4-methylenedioxyformanilide, which is N-methylated using methyl iodide, potassium hydroxide in acetone, and then heated with dilute HCl to yield N-methyl - 3,4 - methylenedioxyaniline hydrochloride which on treatment with dichloracetyl chloride gives dichloracet - 3,4 - methylene dioxy - N - methylanilide; dichloracet - 4 - hydroxy - N - methylanilide is nitrated to the corresponding 3-nitro derivative and reduced with stannous chloride to the 3-amino derivative; similar reduction of dichloracet-N-methyl-4-nitroanilide yields the corresponding 4-amino compound; dichloracet - 4 - hydroxy - 3 - nitro - N - methylanilide is further nitrated with fuming nitric to yield dichloracet - 4 - hydroxy - 3,5 - dinitro - N-methylanilide.  Starting materials.  3,4 - Dihydroxy - N - methylaniline hydrobromide is prepared by refluxing 3,4-dimethoxy-N-methylaniline hydrochloride with aqueous HBr; 3,5-dihydroxy-N-ethylaniline is obtained by treating phloroglucinol with aqueous ethylamine; and N-methyl-m-anisidine by refluxing form-m-anisidide with potassium hydroxide in acetone and then with methyl iodide, finally hydrolysing the product with hydrochloric acid and liberating the base with alkali.  Other intermediates similarly prepared from the corresponding formylated amines are the hydrochlorides of 4 - methoxy - n - propyl-, 4 - n - propoxy - N - methyl-, 4 - allyloxy - N - methyl-, 4 - phenoxy - N - methyl - 2 - methoxy - N - methyl and 2-butoxy -N-methyl-aniline.  The third Provisional Specification further refers to compounds of the above general formula wherein R1 and R2 of the -NR1R2 substituent may represent aralkyl or aryl radicals.