Aniline → 3-Nitro-2-phenylaminobenzoic acid

Participants

Reaction Steps

Reaction scheme 7 illustrates the synthesis of a 1-carboxy N-ethyl phenazine (29a) and 8-methyl 1-carboxy N-ethyl phenazine (29b) derivative. A mixture of aniline (or ortho toluidine) and 2-bromo-3-nitrobenzoic acid is reacted in the presence of CuCl, Cu powder and N-ethylmorpholine in butane-2,3-diol at 70 to 80° C. for 8 to 24 hours. This reaction mixture is diluted with 0.1 M NH4OH solution and filtered through a bed of celite. The resulting solution is slowly poured over into 2N HCl to give N-phenyl-3-nitro anthranilic acid (25a) or the methyl substituted derivative (25b). Intermediates (25a) or (25b) are reacted with sodium borohydride in 2N NaOH solution under reflux conditions to effect ring closure and provide the sodium salt of a phenazine, which, upon acidification, provides (26a) or (26b). The acid chloride of the phenazine 1-carboxy derivative (or 8-methyl 1-carboxyphenazine) is prepared by the reaction with thionyl chloride and the resulting acid chloride is converted to methyl ester by the reaction with methanol in HCl. The resulting phenazine methyl ester (27a) or (27b) is alkylated with diethyl sulfate and potassium carbonate to give corresponding N-ethyl phenazine derivatives (28a) or (28b). Finally, the methyl ester group of phenazines (28a) or (28b) is hydrolyzed with dilute hydrochloric acid to give (29a) or (29b).

Provenance & Evidence