Salicylanilide
is a white, crystalline solid which has found extensive use as a fungicide'-" and bacteriostat". In recent years there has been considerable interest in this product as a starting material for the production of halogenated salicylanilides"~0. Laboratory, pilot plant, and production studies for its synthesis required a knowledge of the impurities present, a method of assay, and methods for the determination of impurities. A review of the literature shows a complete lack of information on this subject.
Salicylanilide is generally produced by the reaction of salicylic acid and aniline in the presence of phosphorus trichloride 718. In addition to the starting materials, four impurities were isolated and identified in salicylanilide. An assay method and methods of analysis for impurities are described in this paper.
Apparattcs and reagents
Spectrophotometric measurements were made on a Cary 15 recording spectrophotometer.
A Cary model r6 spectrophotometer was used for measurements at a single waveleng-th. Silica cells of 1.00 cm path length were used for all ultraviolet spectrophotometric measurements. A Precision Scientific Company, catalogue No. 670 13, autoclave was employed for hydrolysis studies. Continuous flow electrophoresis separations were made on a Beckman Spinco model CP continuous flow electrophoresis cell.
Ion-exchange separations were made on Dowex z-X8, acetate form, 200-400 mesh resin. Preparation of resin, chromatographic columns, and gradient elution equipment have already been described".
Diagnostic thin-layer chromatographic separations were made on o.zs-mm silica gel GFZW thin-layer plates (E. Merck AG, Darmstadt, Germany). Preparative separations employed r.o-mm plates of the same silica gel GFss4 prepared in the laboratory.
A.C.S. methanol was used without further purification. Salicylic acid, methyl salicylate, and aniline of 99% or better purity were used without further purification. 4-Hydroxybenzanilide was prepared by condensing +hydroxybenzoic acid and aniline in the presence of phosphorus trichloride. Salicylsalicylanilide was prepared by con-