Synthesis of 2-Chloromethyl-5-aryl-, 2-Chloromethyl-5-(5-methyl-2-furyl)-, and 2-Chloromethyl-5-(1,5-dimethyl-2-pyrrolyl)-1,3,4-oxadiazoles from Tetrazole Derivatives

Abstract

Acetylation of 5-aryltetrazoles, 5-(5-methyl-2-furyl)tetrazole, and 5-(1,5-dimethyl-2-pyrrolyl)tetrazole with chloroacetyl chloride was studied.1,3,4-Oxadiazoles are key fragments of various drugs, from antiviral agents to antidepressants; they are used as organic scintillators and are components of specialty polymerizing formulations, etc.[1].The goal of this study is the development of a onepot procedure for preparing 5-aryl-2-chloromethyl-1,3,4-oxadiazoles and previously unknown 2-chloromethyl-5-(5-methyl-2-furyl)-and 2-chloromethyl-5-(1,5-dimethyl-2-pyrrolyl)-1,3,4-oxadiazoles from appropriate tetrazole derivatives. These 1,3,4-oxadiazoles are of interest as biologically active substances and reagents for further fine organic synthesis. Similarly to other 1,3,4-oxadiazoles [2], they can be involved in the peptide synthesis by the subsequent reactions with amino acids.2,5-Disubstituted 1,3,4-oxadiazoles of various structures can be prepared by several procedures. The starting compounds can be carboxylic acids and hydrazine; they are converted into diacylhydrazides via several intermediates. The cyclodehydration of diacylhydrazides under the action of POCl 3 yields 1,3,4-oxadiazoles; these compounds can also be prepared by cyclodehydration of diaroylhydrazines and diacylhydrazines under the action of various dehydrating agents (organic acid anhydrides, PCl 5 , H 2 SO 4 [235]).A procedure developed in [6] for preparing 2,5-diaryl-1,3,4-diazoles by the reactions of tetrazoles with benzoyl chlorides in o-xylene or toluene on heating was applied here to the synthesis of 2-chloromethyl-5-aryl-, 2-chloromethyl-5-(5-methyl-2-furyl)-, and 2-chloromethyl-5-(1,5-dimethyl-2-pyrrolyl)-1,3,4-oxadiazoles from tetrazoles and chloroacetyl chloride.Tetrazoles are prepared starting from aromatic and heterocyclic nitriles [7]. Their azidation with NaN 3 is performed in the presence of NH 4 Cl in DMF at 110 3 120oC. Following the procedures from [8310], we prepared 5-phenyltetrazole I, 5-(2-chlorophenyl)tetrazole II, 5-(2-nitrophenyl)tetrazole III, 5-(2-ethoxyphenyl)tetrazole IV, 5-(3-methylphenyl)tetrazole V, 5-(2,4-dimethoxyphenyl)tetrazole VI, 5-(3,4,5-trimethoxyphenyl)tetrazole VII, and also previously unknown 5-(1,5-dimethyl-2-pyrrolyl)tetrazole VIII and 5-(5-methyl-2-furyl)tetrazole IX. The reaction conditions, yields, melting points, and analytical data for

Synthetic Approaches and Pharmacological Activity of 1,3,4-Oxadiazoles: A Review of the Literature from 2000–2012

“…Tetrazole 89 with chloroacetyl chloride ( 90 ) give disubstituted oxadiazole 91 (Entry a , Scheme 34 ) [ 58 ]. Reflux of 4-methoxyphenyltetrazole ( 92 ) with 4- tert -butylbenzoyl chloride for 2 h affords 2-(4- tert -butylphenyl)-5-(4-methoxyphenyl)-1,3,4-oxadiazole ( 93 ) in 96% yield (Entry b , Scheme 34 ) [ 59 ].…”

Utilization of Cyanoacetohydrazide and Oxadiazolyl Acetonitrile in the Synthesis of Some New Cytotoxic Heterocyclic Compounds

“…1,3,4-Oxadiazole derivatives were synthesized via the reaction of hydrazide derivatives using different reagents such as CS 2 [47], POCl 3 /aromatic carboxylic acid [48], thionyl chloride [49][50][51], triphenylphosphine oxide, [52] silica-supported dichlorophosphate [53] and ZrCl 4 [54]. The syntheses of 1,3,4-oxadiazoles via the Huisgen reaction [55,56] is a less popular methodology than the methods mentioned above. On the other hand, Efimova et al reported [57] the synthesis of 1,3,4-oxadiazole derivatives via the acylation of tetrazoles with acetic and benzoic anhydrides.…”

Advances of rejected unsymmetrical dimethylhydrazine(UDMH) reuse technology

“…Experiments [20][21][22] showed that nucleophilic substitution reaction of 5-aryl-2-chloromethyl-1,3,4-oxadiazoles with UDMH produced a series of corresponding chlorides in 64%~84% yield which are all water soluble and biologically active: UDMH involved in the pyrazole cyclization directly in the synthesis process of pyrazole, but it is on the side chain of oxadiazole by nucleophilic substitution reaction in the synthesis of oxadiazoles.…”