GB951940A - A process for producing aromatic ª‡-acylaminoalkyl and aminoalkyl compounds - Google Patents

Abstract

Acylamino compounds which contain the group: -CH(R).NH.CO.R1 directly attached to an aromatic or heterocyclic ring are made by reacting an alkylidene bisamide: <FORM:0951940/C2/1> with the appropriate cyclic compound having a substitutable hydrogen atom in the ring, in the presence of a phosphorus oxyhalide. In the above formulae, R is a hydrogen atom, a lower alkyl group or a phenyl group and R1 is a lower alkyl group or a hydrogen atom. The cyclic compound may have one or more hydroxy, methoxy, nitro, carboxylic or acetylamino substituents. The acylamino compounds, made by the above process, may be hydrolysed to obtain methylamines substituted by cyclic groups. In Example 1, a mixture of phenol, N,N1-methylene bis-acetamide, chloroform and phosphorus oxychloride is refluxed for 4 hours on a water-bath. The mixture is poured into water, and neutralized with sodium bicarbonate. The organic layer is separated, and distilled to remove chloroform. The residue is distilled under reduced pressure to isolate N-(2-hydroxybenzyl)-acetamide and N-(4-hydroxybenzyl)-acetamide. The former amide is hydrolysed with sodium hydroxide solution to obtain 2-hydroxybenzylamine. Example 3 describes the preparation of N-(2-hydroxy-5-nitro-benzyl)-acetamide, and its subsequent hydrolysis to 2-hydroxy-5-nitrobenzylamine. In Example 5, methylene bis-acetamide is reacted with N-2-tolylacetamide, in the presence of phosphorus oxychloride, to give N,N1-diacetyl-2-amino-5-aminomethyl-toluene. Example 8 describes the preparation of N-acetyl-5-amino-methyl-8-hydroxyquinoline. Example 9 describes the preparation of N-acetyl-5-methylamino-2-hydroxy-benzoic acid, and its subsequent hydrolysis to 2-hydroxy-5-aminomethyl-benzoic acid. In Examples 12 and 13, methylene bis-propion-amide and methylene bis-formamide, respectively, are reacted with 2, 4-xylenol to give N-(2-hydroxy-3, 5-dimethylbenzyl)-propionamide and N-(2-hydroxy-3, 5-dimethylbenzyl)-formamide. In Example 14, benzylidene bis-acetamide is reacted with 2, 4-xylenol to give N-(2-hydroxy-3, 5 - dimethyldiphenylmethyl) - acetamide. Example 16 describes the preparation of N-(2-hydroxy-5-nitrodiphenylmethyl)-acetamide, and its subsequent hydrolysis to 2-hydroxy-5-nitro-diphenylmethylamine Examples 7, 10 and 18 describe the preparation of compounds having a benzene ring with a methoxy substituent. Examples 4 and 15 describe the preparation of compounds with a naphthalene ring.