164 KHIIVIIYA GETEROTSIKLICHESKIKH SOEDINENII SYNTHESIS OF HYDROXY DERIVATIVES OF 2, 5-DIARYL-1, 3, 4-OXADIAZOLES V. P. Tkach, A. P. Grekov, V. V. Medvedeva, and K. A. Kornev Khimiya Geterotsiklicheskikh Soedinenii, Vol. 5, No. 2, pp. 218-220, 1969 UDC 547.793.4 A method for the synthesis of hydroxy derivatives of 2, 5-diaryl- 1, 3, 4-oxadiazoles has been developed which consists in the prepara- tion of ocetoxy derivatives of oxadiazole with their subsequent sapon- ification by means of an alcoholic solution of sodium hydroxide. Hydroxy derivatives of 1, 3, 4-oxadiazole are being used in the preparation and stabilization of polymeric materials [1,2], as physiologically active prepara- tions [3, 4], in scintillation techniques [3], etc. The methods for the synthesis of hydroxy derivatives of 1, 3, 4-oxadiazole known in the literature have a par- tial nature in the majority of cases and cannot be regarded as general methods for their preparation [4-6]. In view of this, an investigation of hydroxy derivatives of 2, 5-diaryl-1, 3, 4-oxadiazoles with the objects of finding convenient methods for their syn- thesis and of studying their properties appeared of interest. The present work was devoted to the development of a method for the synthesis of 2-(p-acetoxyphenyl)- and 2-(p-hydroxyphenyl)-5-aryl-1,3, 4-oxadiazoles, which were obtained in accordance with the equation o CH3COOC6H4COCI I[ RCONHNH2 RCONHNHCOC6H4OCCH 3 -- --HCI SOCl~ N--N 0 OH- N--N [I H - O ~--C6H40 E ~ R_C,,oC_C~H40H The diaroylhydrazines were obtained by the reaction of p-acetoxybenzoyl chloride with earboxylic acid hydrazides at room temperature in dry pyridine. When a 1-(p-acetoxybenzoyl)-2-aroylhydrazinewas boiled in an excess of thionyl chloride, hydrogen chlo- ride and sulfur dioxide were liberated and a 2-acetoxy- benzoyl-5-aryl-1, 3, 4-oxadiazole was formed. The cyelodehydration of the 1-acetoxybenzoyl-2-aroylhy- drazines can also be effected in phosphorus oxyehlo- ride. However, in this case, side reactions evidently take place which affect the purity of the resulting product. When an equimolecular amount of sodium hydroxide was added to an ethanolic solution of a 2-acetoxy- phenyl-5-aryl-1, 3, 4-oxadiazole, saponification of the acetoxy group took place. The resulting 2-hydroxy- phenyl-5-aryl-1, 3, 4-oxadiazole was isolated by acid- ifying the reaction mixture with hydrochloric acid. This did not lead to the cleavage of the oxadiazole ring, as takes place in the alkaline saponification of 2-(p- ethoxycarbonylphenyl)-5-phenyl-1,3, 4-oxadi azole where, in addition to the hydrolysis of the ester group- ing, the opening of the oxadiazole ring takes place with the formation of the corresponding 1-benzoyl-2-(p- carboxybenzoyl)hydrazine [7]. In the case of 2-(p- acetoxyphenyl) -5-(p-ethoxycarbonylphenyl)-l,3, 4- oxadiazole, hydrolysis is likewise accompanied by the cleavage of the oxadiazole ring. EXPERIMENTAL 1-(p-Acetoxybenzoyl)-2-aroylhydrazines. A 50-ml three-necked flask fitted with a mechanical stirrer, dropping funnel, calcium chloride tube, and thermometer was charged with 0.l mole of a carboxylic acid hydrazide and 10-15 ml of dry pyridine. To the resulting solution, with stirring and cooling, 0.1 mole of p-acetoxy- benzoyl chloride in 5-8 ml of dry benzene was slowly added. The temperature of the reaction mixture was kept between 20~ and 26~C. Then the mixture was stirred for 30 rain, the benzene was distilled off in the vacuum of a water pump, and the contents of the flask were treated with water. The crystalline product that separated out was filtered off and was washed with water, 3% hydrochloric acid, and water again to neutrality. The diaroylhydrazines obtained form colorless substances sparingly soluble in water and in aliphatie and aromatic hydrocarbons (see Table 1). 2-(p-Acetoxyphenyl)- 5-a~yl-1, 3, 4-oxadtazoles. A round-bot- tomed flask fitted with a reflux condenser and a bubble counter was charged with 1-(p-acetoxybenzoyl)-2-aroylhydrazine and a tenfold amount (by weight) of thionyl chloride. The initial hydrazine dis- solved completely with the evolution of hydrogen chloride and sulfur dioxide. After the end of the reaction, the excess of thionyl chlorides was distilled off. The contents of the flask were treated with water and the precipitate that separated was filtered off, dried, and crys- tallized. This process gave pure acetoxyoxadiazoles which formed colorless crystalline substances insoluble in water and readily soluble in aromatic hydrocarbons (see Table 2). 5-Azyl-2-(p-hydroxyphenyl)-l,3,4-oxadtazoles. A solutionof 1 mM of a 2-(p-acetoxyphenyl)-5-aryl-1, 3, 4-oxadiazole in 20-30 Table 1 1-(p-Acetoxybenzoyl)-2-aroylhydrazinesCH3COOCsH4CONHNHCOR C8H5 ~-CH3CsH4 p-CHsC6H4 o-NO2C~H4 ~-NO2C6H4 p-C2HsOOCCsH4 Mp, ~ 192 191--192 198--199 225--226 228--229 202--204 Solvent for crystallization Methanol Methanol Methylethylketone Methanol MethyleellosoNe Methanol Empkical formula CmHI4N204 CtTHIsN204 C17HIsN204 CIsHmN30~ C~sHlsNsO6 CmHIsN~O~ N,~ / Yield, calcu- % found lated - ] 9,29 9.39 [ 92 8,96 8.97 I 90 9.07 8.97 / 98 12,36 12.241 91 12.20 12.24 95 7.92 7.95 91