Synthesis by Phase Transfer Catalysis of N-Benzyl, N-Diphenylmethyl and N-Triphenylmethyl Azoles and Benzazoles: Proton NMR and Chromatographic Data as a Tool for Identification

Pyrazole, imidazole, 1.2.4-triazole, indaaole and benzotriazale were alkylated under phase transfer catalysis IPTCI with beneyl-, diphenylmethyl-and trityl chloride.Alkylation occurred only at the ring nitrogen atoms of the heterocycle, except for indazole in which substitution took also place at position 3.A systematic study of the Nand C-substituted derivatives by proton NMR and chromatographic techniques has been done.This work is concerned with the preparation of N-substituted derivatives of azoles, 1analogous to the widely used antifungal agent chlotrimazole .All products studied are assembled in Scheme L unless s. and that had not been obtained in our reaction conditions: alkylation of the azole or its benzo derivative under liquid-liquid or solid-liquid phase transfer catalysis 2'3'4 using equimolecular amounts of the reactants (azole or benzaaole 1 : alkylating agent 1).tetrabutylammonium bromide or bisulfate as catalyst and xylene as the solvent.Far the reaction of azoles with simpler halides in the presence of PTC see reference 5.When the starting materials were pyrazole, imidazole.1.2.4-triazole and benzotriazole only N-substituted derivatives were formed with the three alkylating agents: benzyl-, diphenylmethyl and trityl chloride.Relative percentages showing the re- gioselectivity of the reaction are gathered in Table 1 and are in agreement with the general reactivity of five membered aromatic nitrogenated heterocycles that 5 possess several nucleophilic sites .1-Benzyl-and 2-benzylindazoles had been prepared previously by von Auwers6 in 1921 from indazale and benzyl chloride in ethanol-sodium ethoxide.This author se- parates the two isomers and describes the physical characteristics of the bases and their picrates, but does not provide any chemical support to the assignment made.We have reprepared the picrate of 2-benzylindazole obtained by PTC, whose Structure was confirmed by proton NMR spectroscopy, checking that the previous attribution made by von Auwers was correct.