Acetic Anhydride → 2-Acetamido-1-acetoxy-4,5-dimethylbenzene

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The diamino compound required as intermediate is synthesised in the following manner from 2-amino-4,5-dimethylphenol (see E. Diepolder, Chem. Ber., 42, 2916/1909). This phenol compound is acetylated with acetic anhydride in ethyl acetate/pyridine to give 2-acetamido-1-acetoxy-4,5-dimethylbenzene (m.p. 156°-158° C.) which is nitrated in acetic anhydride with 100% nitric acid in acetic anhydride at 20° C. From the nitration mixture there is isolated, in 43% yield, 2-acetamido-1-acetoxy-4,5-dimethyl-3-nitrobenzene; m.p. 209°-211° C. After saponification of this compound in 2 N hydrochloric acid, there is isolated 2-amino-4,5-dimethyl-3-nitrophenol; m.p. 176°-178° C. This compound is converted into the sodium salt with a methanolic solution of sodium methylate. This salt is reacted in dioxan/dimethylformamide with excess 3-chloro-1,2-epoxypropane at 75° C. After evaporation, the residue is taken up in chloroform, treated with water and active charcoal and freed from solvent. The amorphous residue of 2-amino-4,5-dimethyl-1-(2,3-epoxypropoxy)-3-nitrobenzene is reacted in boiling ethanol with tert.-butylamine to give 2-amino-4,5-dimethyl-1-(2-hydroxy-3-tert.-butylaminopropoxy)-3-nitrobenzene. This compound is then quantitatively hydrogenated in ethanol over platinum dioxide to give 2,3-diamino-4,5-dimethyl-1-(2-hydroxy-3-tert.-butylaminopropoxy)-benzene, which is isolated as its trihydrochloride.

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