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

Abstract

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 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.

Acetylene as a Dicarbene Equivalent for Gold(I) Catalysis: Total Synthesis of Waitziacuminone in One Step

“…Herein, we report the use of acetylene gas in intermolecular gold(I)‐catalyzed reactions leading, stereoselectively, to Z , Z ‐dienes 4 , biscyclopropanes 5 , and tricyclo[5.1.0.0 2,4 ]octanes 6 (Scheme ). Acetylene was conveniently produced in situ in small quantities from calcium carbide and water using a Y shaped two‐chamber flask …”

Calcium‐Based Sustainable Chemical Technologies for Total Carbon Recycling

“…with acetylene generation and the reaction mixture separated into different compartments (Figure C). This approach is useful for reaction mixtures sensitive to water and calcium salts . Potentially, such a setup should be compatible with different reaction types because direct contact of the reaction mixture and acetylene generation mixture is avoided.…”

“…Synthesis of 1,3-disubstituted pyrazoles from in situ generated nitrile imines and acetylene is carried out in as imple twochamber reactor. [26] One part of the reactori sl oaded with hydrazonoyl chloride precursors of active nitrile imine species and ab ase. The other part is used to generate acetylene from CaC 2 andw ater (Scheme5).…”

“…This approach is useful for reaction mixtures sensitivet ow ater and calcium salts. [26] Potentially,s uch as etup should be compatible with different reaction types because direct contact of the reactionm ixture and acetylene generation mixture is avoided. Direct reactioni nt he solid state ( Figure 2D)h as advantages in terms of powerful mechanochemical activation and as olvent-free approach.…”

Acetylene in Organic Synthesis: Recent Progress and New Uses

“…Cycloaddition reactions with acetylene ( Scheme 1 , path h ) provide a shortcut to isoxazoles, pyrazoles, and triazoles [ 41 , 42 , 43 , 44 ]. This segment of acetylene chemistry is especially promising for obtaining novel heterocyclic molecules.…”