Synthesis of 1-(R-Phenyl)-5-(R-Methyl)-1H-1,2,3-triazole-4-carboxylic Acids by One-Pot Tandem Reaction

Abstract

Substituted 1H-1,2,3-triazole-4-carboxylic acids were synthesized by a three-component reaction of arylazides, ethyl 4-chloro-3-oxobutanoate, and either O- or S-nucleophiles in the presence of a base catalyst. The reaction most probably proceeded as a [3 + 2] cyclocondensation reaction between arylazide and ethyl 4-chloro-3-oxobutanoate with the further nucleophilic substitution of chlorine in the chloromethyl group. Reaction optimization was performed to carry out the reaction with an O-nucleophile. Conditions were found under which diethyl 2,5-dihydroxyterephthalate (the product of self-condensation of two molecules of ethyl 4-chloro-3-oxobutanoate with the further oxidation by azide) was obtained.

Keywords:

• Azides
• cyclocondensation
• multicomponent reactions
• 1H-1,2,3-triazoles

Notes

^a Isolated yields of acids 6a–j when the reaction occurred in a boiling solution.

Note. Conditions: sodium (0.25 g, 11 mmol); 5 mmol of azide 1, ester 2, and nucleophile 4; MeOH (20 mL).

^a Isolated yields of acids 6a, b, and d.

^b Boiling solution.