Patent GB-360957-A (GB)
Title: Manufacture of arsenobenzene compounds
IPC: C07F9/70
Filed: 1930-08-12
Abstract: Arseno compounds; arsinic acids; arsenoxides and arsines.--Asymmetrical arseno compounds containing a p  --OCH2.COOH group and a substituted amino group are prepared by (1) reducing a phenoxyacetic acid-arsinic acid or an arylarsinic acid having an imidazole ring containing a glycollic acid residue with another arylarsinic acid, (2) converting the corresponding trivalent arsenic compounds, e.g. arsines and arsenoxides, into the said products by known methods, or (3) treating a symmetrical or asymmetrical arseno compound containing an hydroxyl group with a limited amount of chloracetic acid; in each case, at least one of the components contains an amino or substituted amino group, whilst in cases in which the product contains a free amino group it is either treated with an acylating agent or condensed with formaldehydebisulphite, glycide, &c.  The products possess therapeutic properties.  According to the examples, (1) 4-acetylamino-2 : 3 - dimethyl - 1 - phenylpyrazolone-p-arsinic acid (obtained by acetylating the 4-amino compound, which is itself prepared by reduction of the corresponding nitroso compound) and 1-methyl-2-hydroxyacetic acid-benzimidazole-5-arsinic acid (prepared by interaction of 1-methylbenzimidazolone-5-arsinic acid with chloracetic acid) are reduced with hypophosphorous acid; (2) 2-methyl-4-phenoxyacetic acid-1-arsinic acid (obtained by treating 2-methyl-4-hydroxybenzene-1-arsinic acid with chloracetic acid) is reduced with hydrosulphite in the presence of 3-acetylamino-4-hydroxybenzene-1-arsinic acid; (3) 3-hydroxybenzaldehyde semicarbazone-4-arsinic acid and 3-acetylamino - 4 - phenoxyacetic acid - 1 - arsinic acid (obtained by causing chloracetic acid to react upon 3 - acetylamino-4 - hydroxybenzene - 1 - arsinic acid) are together reduced with hypophosphorous acid; (4) 3-amino-4-hydroxybenzene-1-arsinic acid and 3-methyl-4-phenoxyacetic acid-1-arsinic acid (formed by interaction of 3-methyl-4-hydroxybenzene-1-arsinic acid and chloracetic acid) are reduced with hypophosphorous acid and the resulting arseno compound then converted into its formaldehyde-sodium bisulphite compound; (5) the arseno compound resulting from the hydrosulphite reduction of 3-amino-4-hydroxybenzene-1-arsinic acid in admixture with 1-methyl-2-hydroxyacetic acid-benzimidazole-5-arsinic acid is converted into its formaldehyde-sodium bisulphite compound; (6) 3-acetylamino-4-hydroxybenzene-1-arsinic acid and 3-acetylamino-4-phenoxyacetic acid-1-arsinic acid are reduced with sodium hydrosulphite; (7) 2-methyl-4-phenoxyacetic acid-1-arsinic acid and 4-amino - 2 : 3 - dimethylpyrazolone (5) - 1 - phenyl-p-arsinic acid are reduced with hydrosulphite and the arseno compound treated with formaldehyde and sodium bisulphite; (8) the formaldehyde-sodium bisulphite compound is prepared from the hydrosulphite reduction product of 3-acetylamino-4-phenoxyacetic acid-1-arsinic acid and 4-amino-2 : 3-dimethylpyrazolone (5)-1-phenyl-p-arsinic acid; (9) an arseno compound is prepared by reduction with hydrosulphite of 1-methyl-2-hydroxyacetic acid-benzimidazole-5-arsinic acid and 3-acetylamino-4-hydroxybenzene-1-arsinic acid; (10) 4-acetylamino-2-phenoxyacetic acid-1-arsinic acid (prepared by reaction between 2-hydroxy-4-acetylaminobenzene-1-arsinic acid and chloracetic acid) and 3-acetylamino-4-hydroxybenzene-1-arsinic acid are reduced with hydrosulphite; (11) the arseno compound of example 8 is treated with glycide, which condenses with the free amino group; (12) 3-methyl-4-phenoxyacetic acid-1-arsinic acid (prepared from 3-methyl-4-hydroxybenzene-1-arsinic acid and chloracetic acid) and 3-acetylamino-4-phenoxyacetic acid-1-arsinic acid are reduced with hypophosphorous acid; (13) the arseno compound obtained by reduction of 4-amino-2 : 3-dimethylpyrazolone (5)-1-phenyl-p-arsinic acid and 1-methyl-2-hydroxyacetic acid-benzimidazole-5-arsinic acid with hydrosulphite, is converted into its formaldehyde-sodium bisulphite compound; (14) 4-amino-2 : 3-dimethylpyrazolone (5)-1-phenyl-p-arsinic acid and 3-methyl-4-phenoxyacetic acid-1-arsinic acid are reduced with hydrosulphite and the arseno product transformed into the formaldehydesodium bisulphite compound; (15) 2-methyl-4-glycollylaminobenzene-1-arsinic acid (obtained by treating 2-methyl-4-aminobenzene-1-arsinic acit with chloracetyl chloride and boiling the producd with alkali) and 1-methyl-2-hydroxyacetic acidbenzimidazole-5-arsinic acid are reduced with hypophosphorous acid; (16) 3-acetylamino-4-phenoxyacetic acid-1-arsenoxide (prepared by reducing the arsinic acid with sulphur dioxide in presence of hydrogen iodide) is treated with 3-acetylamino-4-hydroxybenzene-1-arsine (obtained by acetylating 3-amino-4-hydroxybenzene-1-arsine); (17) 3-acetylamino-4-hydroxy-5-chlorobenzene-1-arsinic acid and 3-acetylamino-5-chloro-4-phenoxyacetic acid-1-arsinic acid are reduced with hypophosphorous acid; (18) 3 : 3<1>-diacetylamino-4 : 4<1>-dihydroxy-5 : 5<1>-dichloroarsenobenzene is treated with 1 mol. of chloracetic acid; (19) 3 : 3<1>-dihydroxy-4 : 4<1>-diacetylaminoarsenobenzene (obtained by acetylating 4 - amino - 3 - hydroxybenzene-1-arsinic acid and reducing with hydrosulphite) is heated with 1 mol. of chloracetic acid; (20) 2 : 2<1>-diacetylamino-3 : 3<1>-dihydroxy-4 : 4<1>-dichloroarsenobenzene (obtained by reducing 2-nitro-3-hydroxy-4-chlorobenzene-1-arsinic acid and acetylating the product) is treated with 1 mol. of chloracetic acid.  The Provisional Specification includes also the following examples: (1)1-methyl-2-hydroxyacetic acid-benzimidazole-5-arsinic acid and 1-methylbenzimidazolone-5-arsinic acid are reduced to the arseno compound with hydrosulphite; (2) 1-methyl-2-hydroxyacetic acid-benzimidazole-5-arsinic acid and 2-methylphenoxyacetic acid-1-arsinic acid are reduced with hypophosphorous acid; (3) the arseno compound is prepared by reduction with hypophosphorous acid of 1-methyl-2-hydroxyacetic acidbenzimidazole-5-arsinic acid and 3-hydroxybenzaldehyde semicarbazone-4-arsinic acid; (4) 2-hydroxymethylbenzimidazole-5-arsinic acid (obtained by heating 3 : 4-diaminobenzene-1-arsinic acid with glycollic acid) and 1-methyl-2-hydroxyacetic acidbenzimidazole-5-arsinic acid are reduced with hydrosulphite.