Synthesis and Characterization of 1,4-Benzodioxane-6-Carboxylic Acid Amide Analogs

A library of new 1,4-benzodioxane-6-carboxylic acid amide analogs was designed and synthesized. These analogs were obtained in six steps from gallic acid. Firstly, esterification of the commercially available gallic acid in methanol in the presence of sulfuric acid afforded methyl 3,4,5-trihydroxybenzoate (9) in satisfactory yield. The ester 9 was then reacted with an excess of 1,2-dibromoethane in the presence of K2CO3 in acetone to furnish the 6,8-disubstituted-1,4-benzodioxane (10) in 45% yield. The reaction of 10 with various mercaptans gave the sulfide derivative 11, 12, and 13 in moderate yield. Subsequent hydrolysis of the methyl ester in 13 followed by conversion to the acid chloride and reaction of the acid chloride intermediate with different commercially available primary and secondary amines gave the amide analogs 18 - 32 with an average yield of 43%. Conversion of the sulfide group in Compound 23 to Sulfoxide 33 or Sulfone 34 was accomplished by reaction with either 30% H2O2/TeO2 or 30% H2O2, respectively. The structures of the synthesized compounds were characterized using FTIR, 1H-NMR, 13C-NMR, and high-resolution ESI-MS.