Synthetic Antimicrobials. II. Synthesis of Pyrazolo [1, 5-a] pyridine Derivatives. (1)

2-Alkyl-3-acyloxypyrazolo [1, 5-a] pyridines (III) were prepared by refluxing 1-amino-2-hydroxymethylpyrioinium chloride (Ia) in excess acyl anhydride in the presence of a base. III were converted into 2-alkyl-3-hydroxy derivatives (IVa-f) by acid hydrolysis. Ia was refluxed with ethyl orthoformate in acetic acid containing sodium acetate to give 3-hydroxy derivative (IVg). Reaction of Ia with benzoyl chloride in H2O-K2CO3 gave mainly O, N-dibenzoyl ylide (VIIa) and 2-phenyl-3-benzoyloxypyrazolo [1, 5-a] pyridine (IXa). Pyrolysis of VIIa gave 2-phenyl-3-hydroxy derivative (VIIIa), which was also obtained from 1-ben-zimido-2-hydroxymethylpyridine (VIa) by treatment with H2SO4, followed by alkali treatment. Further the compound (VIIIa) was prepared by the reaction of 1-benzimido-2-picoline (XVIIa) with I2 in pyridine. Analogously various 2-substituted-3-hydroxy derivatives (VIIIb-1 and IVa) were obtained. 1-Anilinothiocarbonylimino-2-hydroxymethylpyridine (XIXa) was converted into cyclic pyridinium salt (XXa) by treating with H2SO4, and XXa was treated with K2CO3 to give 2, 2'-dianilinopyrazolo [1, 5-a] pyridine-3, 3'-disulfide (XXIIa). XXIIa was converted into 2-anilino derivative (XXIIIa) by Raney Ni reduction. Analogously 2-benzamido derivative (XXIIIb) was obtained from 1-benzamidothiocarbonylimino-2-hydroxymethylpyridine (XIXa) by the same procedure. 2-Acetamido derivative (XXIX) was obtained by heating pyridine-2-acetamidoxime (XXVII) with acetic anhydride. The compounds (XXIIIa and XXIX) were also converted into the corresponding 3-thiocyano and 3-nitro derivatives (XXIV, XXV, XXXIb and XXXIc). The tuberculostatic activities of the pyrazolo [1, 5-a] pyridine derivatives were also indicated.