Mechanistic Insights on Azide−Nitrile Cycloadditions: On the Dialkyltin Oxide−Trimethylsilyl Azide Route and a New Vilsmeier−Haack-Type Organocatalyst

Abstract

The mechanism of the azide-nitrile cycloaddition mediated by the known dialkylltin oxide-trimethylsilyl azide catalyst system has been addressed through DFT calculations. The catalytic cycle for this tin/silicon complex-based mechanism has been thoroughly examined, disclosing the most plausible intermediates and the energetics involved in the rate enhancement. In addition, a new catalyst, 5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide, is presented for the formation of tetrazoles by cycloaddition of sodium azide with organic nitriles under neutral conditions. The efficiency of this organocatalyst, generated in situ from N-methyl-2-pyrrolidone (NMP), sodium azide, and trimethylsilyl chloride under reaction conditions, has been examined by preparation of a series of 5-substituted-1H-tetrazoles. The desired target structures were obtained in high yields within 15-25 min employing controlled microwave heating. An in depth computational analysis of the proposed catalytic cycle has also been addressed to understand the nature of the rate acceleration. The computed energy barriers have been compared to the dialkylltin oxide-trimethylsilyl azide metal-based catalyst system. Both the tin/silicon species and the new organocatalyst accelerate the azide-nitrile coupling by activating the nitrile substrate. As compared to the dialkylltin oxide-trimethylsilyl azide method, the organocatalytic system presented herein has the advantage of higher reactivity, in situ generation from inexpensive materials, and low toxicity.

Tetrazole substituted polymers for high temperature polymer electrolyte fuel cells

“…To enhance the reaction kinetics, usually acidic catalysts are added. 32 An apparently safe procedure for the kilogram scale was reported by Girardin et al 33 As shown by Du et al, also aromatic nitrile group containing polymers can react with sodium azide in a polymer analogous reaction. large head space in which hydrazoic acid remains under the detonation threshold of 15 000 ppm), the potential evolution of HN 3 may raise safety issues especially for larger batches.…”

Microwave-Assisted Syntheses in Organic Chemistry

“…The catalyst (5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide) was formed in situ. The cycloaddition of azides with organic nitriles resulted in a series of 5-substituted-1H-tetrazoles in high yields (Scheme 2.60) [96].…”

Microwave Reactors: A Brief Review on Its Fundamental Aspects and Applications

“…7) Sequential coupling-imination-annulation reactions of ortho-bromoarylaldehydes and terminal alkynes with ammonium acetate in the presence of a palladium catalyst under microwave irradiation furnishes different substituted isoquinolines, furopyridines and thienopyridines in good yields [68]. 8) MW irradiation of the nitrile substrates by the Brønsted or Lewis acid catalyst has been found to be responsible for rate enhancement in azide-nitrile cycloaddition [69]. Lewis acids such as Zn or Al salts perform in a similar manner, activating the nitrile moiety and leading to an open-chain intermediate that subsequently cyclizes to produce the tetrazole nucleus.…”