[3+2]-Cycloaddition of in Situ Generated Nitrile Imines and Acetylene
A novel synthetic methodology for the preparation of 1,3-disubstituted pyrazoles from in situgenerated 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 CaC2 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.
Reference: J. Org. Chem., 2018, ASAP
DOI: 10.1021/acs.joc.8b00155
On-line version: https://pubs.acs.org/doi/10.1021/acs.joc.8b00155
