Formation of pyrazol‐1,3,4‐thiadiazoles through 1,3‐dipolar cycloadditions of 3‐thioxo‐[1,2,4]‐triazepin‐5‐one with nitrilimines: an experimental and computational study

Abstract

In this work the results of experimental and computational study of the title compounds and some ancillary compounds are reported. Two bicyclic pyrazol-1,3,4-thiadiazole derivatives were synthesized by reaction between 6-dimethylaminomethylene-3-thioxo-[1,2,4]-triazepin-5-one 1 and several nitrilimines 2a-f to give corresponding spirocycloadducts 3a-f, which undergo a rapid rearrangement leading to the new bicyclic compounds, 4a-f and 5a-f.These obtained bicyclic products were characterized by 1 H and 13 C NMR spectroscopy and finally by X-ray crystallography. Theoretical calculations have been carried out using DFT methods to rationalize the formation of the two new bicyclic compounds. Two reaction types are involved in the formation of the compounds 4a-f and 5a-f. The first one is a 1,3-dipolar cycloaddition reaction between 1 acting as dipolarophile and 2a-f as dipoles. The results indicate that the cycloaddition between 1 and 2g, as model of 2a-c, takes place via a high asynchronous bond-formation process. The regioselectivity obtained from the calculations is in complete agreement with the formation of the unique spirocycloadducts 3a-f. The second reaction leading to the formation of the final products is a domino process that is initiated by the quick and irreversible cleavage in a catalytic acid environment of triazepenic ring. Messaoudi 1975Messaoudi -2003 2 ¤ dedicated to the memory of Tourya El

Computational Insight into the Carbenic Character of Nitrilimines from a Reactivity Perspective

“…6 Previous efforts using computational chemistry to shed light on cycloaddition reactions from nitrilimines seem to have been focused almost entirely on their [3+2] cycloadditions. Thus, regioselectivity has been probed through a comparison of transition state energies, 14,15 and an understanding has been sought using reactivity indices. 16 Transition state energies have ABSTRACT: Nitrilimines (R-CNN-R) can be described through a carbenic valence bond structure, and although intermolecular carbenic reactions from nitrilimines are unknown, intramolecular reaction products from ortho-vinyl MeCOO-CNN-Ph (1) and Ph-CNN-Ph (2) that seem to have followed two typical carbene reaction mechanisms, [1+2] cycloaddition and C-H insertion, have been reported.…”

“…17 Addition of MeCOO-CNN-Ph to a CdS moiety required a B3LYP/6-31G(d) gas phase activation energy around 3.5 kcal mol À1 for attack from the electron rich sulfur onto the electrophilic CNN carbon atom. 15 The regioisomeric C 3 3 3 C interaction, on the other hand, was determined to be a relatively high-energy process, with a barrier of about 21 kcal mol À1 . 15 In contrast, for the [3+2] cycloaddition of MeCOO-CNN-Me to indenone determined with B3LYP/6-311G(d), the transition states with their C 3 3 3 C interactions leading to the two regioisomers are closer in energy, 5.4 and 9.0 kcal mol À1 .…”

“…15 The regioisomeric C 3 3 3 C interaction, on the other hand, was determined to be a relatively high-energy process, with a barrier of about 21 kcal mol À1 . 15 In contrast, for the [3+2] cycloaddition of MeCOO-CNN-Me to indenone determined with B3LYP/6-311G(d), the transition states with their C 3 3 3 C interactions leading to the two regioisomers are closer in energy, 5.4 and 9.0 kcal mol À1 . 14 For the intramolecular [3+2] cycloaddition of RCOO-CNN-Ph, where R = (S)ÀCH 2 dCH-CHMeÀ, relative energies for the two diastereomeric transition states from MP2/cc-PVDZ are 4.6 and 5.9 kcal mol À1 and drop to as low as 2.7 kcal mol À1 for a single point energy calculation with the aug-cc-PVDZ basis set.…”

“…Previous efforts using computational chemistry to shed light on cycloaddition reactions from nitrilimines seem to have been focused almost entirely on their [3+2] cycloadditions. Thus, regioselectivity has been probed through a comparison of transition state energies, , and an understanding has been sought using reactivity indices . Transition state energies have been compared to rationalize an observed stereoselectivity in enantiomerically pure tethered nitrilimines .…”

“…With PBE0/6-311++G(2df,pd), the corresponding zero-point vibrational corrected activation energy was reported at 8.4 kcal mol –1 . Addition of MeCOOCNNPh to a CS moiety required a B3LYP/6-31G(d) gas phase activation energy around 3.5 kcal mol –1 for attack from the electron rich sulfur onto the electrophilic CNN carbon atom . The regioisomeric C···C interaction, on the other hand, was determined to be a relatively high-energy process, with a barrier of about 21 kcal mol –1 .…”