5-Halo-1,2,3-triazoles - important heterocycles in biochemistry and pharmacy - can be synthezised by reaction of α-diazonitriles with hydrogen halides. The effect of substituents on the ease of this cyclization reaction is investigated experimentally and computationally. Computed enthalpies of activation are in good agreement with experimental data: ΔH^≠_calc = 21 kcal/mol; ΔH^≠_exp = 21 kcal/mol for 2-cyano-2-diazoacetamide. Considerably larger enthalpies of activation are calculated for 2-diazo-4,4,4-trifluoro-3-oxo-butyronitrile and 2-diazomalononitrile, ΔH^≠_calc ≥ 30 kcal/mol; no cyclization of these diazo compounds to the triazole is observed experimentally. The reaction proceeds in two steps: first, in the rate determining step, a hydrogen halide adduct is formed; the second step consists in the cyclization of these intermediates to the triazoles. Calculated enthalpies of activation for this second step are < 10 kcal/mol. The first step can be interpreted as a strongly asynchronous [2+2] cycloaddition of the hydrogen halide onto the triple bond of the nitrile group and the second one as a pseudopericyclic heteroelectrocyclization reaction. The overall reaction is strongly exothermic, ΔH^react_calc = -15 kcal/mol.

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1. Centipedolide A: Isolation, Structure and Absolute Configuration