TY - JOUR

T1 - [3 + 2]-Cycloaddition of in Situ Generated Nitrile Imines and Acetylene for Assembling of 1,3-Disubstituted Pyrazoles with Quantitative Deuterium Labeling

AU - Воронин, Владимир Владимирович

AU - Ледовская, Мария Сергеевна

AU - Гордеев, Евгений

AU - Родыгин, Константин Сергеевич

AU - Анаников, Валентин Павлович

N1 - Funding Information: Experimental work was supported by Russian Science Foundation (RSF grant 16-13-10301). Theoretical study was supported by Russian Foundation for Basic Research (grant 17-03-01148). The authors also express their gratitude to the Resource Centers of Saint Petersburg State University: Magnetic Resonance Research Centre; Chemical Analysis and Materials Research Centre.

PY - 2018/4/6

Y1 - 2018/4/6

N2 - A novel synthetic methodology for the preparation of 1,3-disubstituted pyrazoles from in situ generated nitrile imines and acetylene is reported. The reactions are performed in a simple two-chamber reactor. One part of the reactor is loaded with hydrazonoyl chloride precursors of active nitrile imine species and a base. The other part is used to generate acetylene from CaC 2 and water. Partitioning of the reactants improves the yields of desired pyrazoles up to 99% and simplifies their isolation to a simple procedure of solvent evaporation. The approach requires no complex equipment and utilizes inexpensive, safe, and easy to handle calcium carbide as a starting material. A model deuterium incorporation is carried out according to the developed methodology, producing a series of novel 4,5-dideuteropyrazoles with excellent deuterium enrichment. Theoretical calculations on reaction mechanism and characterization of possible intermediate structures were performed.

AB - A novel synthetic methodology for the preparation of 1,3-disubstituted pyrazoles from in situ generated nitrile imines and acetylene is reported. The reactions are performed in a simple two-chamber reactor. One part of the reactor is loaded with hydrazonoyl chloride precursors of active nitrile imine species and a base. The other part is used to generate acetylene from CaC 2 and water. Partitioning of the reactants improves the yields of desired pyrazoles up to 99% and simplifies their isolation to a simple procedure of solvent evaporation. The approach requires no complex equipment and utilizes inexpensive, safe, and easy to handle calcium carbide as a starting material. A model deuterium incorporation is carried out according to the developed methodology, producing a series of novel 4,5-dideuteropyrazoles with excellent deuterium enrichment. Theoretical calculations on reaction mechanism and characterization of possible intermediate structures were performed.

UR - http://www.scopus.com/inward/record.url?scp=85045097358&partnerID=8YFLogxK

U2 - 10.1021/acs.joc.8b00155

DO - 10.1021/acs.joc.8b00155

M3 - Article

VL - 83

SP - 3819

EP - 3828

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 7

ER -