Thermolysis of Triazoles as Melts − Is the 3,5-Diphenyl-1,2,4-triazole Group a Good Leaving Group?

Abstract

The mechanism of the rearrangement of 4‐alkyltriazoles to the corresponding 1‐alkyltriazoles on thermolysis at 330 °C is shown to involve initial formation of an intermediate 1,4‐dialkyltriazolium triazolate salt. The triazolate ion subsequently attacks at the alkyl group bearing 1‐ and 4‐positions of the dialkyltriazolium ion, yielding the observed products. No evidence for unimolecular reaction steps has been found. The triazole moiety in these compounds is only a weak leaving group, which requires activation by alkylation. Unimolecular reaction steps never take place, neither from neutral triazole species nor from activated dialkyl‐substituted triazolium species.

Regioselectivity in the Thermal Rearrangement of Unsymmetrical 4-Methyl-4H-1,2,4-triazoles to 1-Methyl-1H-1,2,4-triazoles

“…The rearrangement of 4-methyl-3,5-diaryl-4 H -1,2,4-triazoles to the corresponding 1-methyl-3,5- diaryl-1 H -1,2,4-triazoles exhibited regioselectivity comparable to that for the alkylation of 3,5-diaryl-1 H -1,2,4-triazoles, providing further support to the previously proposed mechanism for the rearrangement [ 19 ], which would involve consecutive nucleophilic displacements steps ( Scheme 3 ).…”

1,2,4-Triazoles: Synthetic approaches and pharmacological importance. (Review)

“…The general reactions are shown in Scheme 5. The rearrangement of 3,5-diaryl-4-methyl-4H-1,2,4-triazoles to the corresponding 3,5-diaryl-1-methyl-1H-1,2,4-triazoles exhibited a regioselectivity comparable to that for alkylation of 3,5-diaryl-1H-1,2,4-triazoles, providing further support to the previously proposed mechanism for the rearrangement [61], which would involve consecutive nucleophilic displacement steps (Scheme 6). Nair et al [62] recently reported an extensive review on the synthesis of 1,2,4-triazoles and thiazoles from thiosemicarbazide and its derivatives.…”

A Simple Protocol for the Stereoselective Construction of Enaminyl Sulfonyl Fluorides

“…However, due to the properties of amine as both a nucleophile and a base, as well as the different reactivity of the two leaving groups, the sequence of substitution and elimination reaction on the new reagent and the preference for substitution on the primary carbon or secondary carbon were difficult to determine, which could result in the formation of a series of unexpected byproducts I – IX (Scheme ). In theory, triazole and bromide both can act as leaving groups, and the triazole group was less reactive than bromide when it was connected with saturated carbon . Therefore, we anticipated that with the promotion of base (amines) intermediate I could be generated initially followed by sequential Michael addition and elimination to provide the desired N -ESF.…”

“…Quantitative yields of 3b and 4-phenyl-1 H -1,2,3-triazole 6 were generated under the standard reaction conditions (Scheme , a). When a similar starting material 7 without the substitution of bromine atom was used (Scheme , b), only the SuFEx reaction occurred with 98% yield of sulfamide 8 generated, which revealed that the triazole group was not reactive enough as a leaving group when it was connected directly with a saturated carbon . Interestingly, when pure ( E )-2-(4-phenyl-1 H -1,2,3-triazol-1-yl)­ethene-1-sulfonyl fluoride I (for more details, see the SI) was used, the corresponding 3b and triazole 6 were obtained in 96% and 95% yields, respectively (Scheme , c), which indicated vinyl triazole I was a key intermediate during the formation of N -ESF.…”