Regioselective Synthesis, NMR, and Crystallographic Analysis of N1-Substituted Pyrazoles

Article abstract of DOI:10.1021/acs.joc.7b01006

A systematic study of the N-substitution reactions of 3-substituted pyrazoles under basic conditions has been undertaken. Regioselective N1-alkylation, -arylation, and -heteroarylation of 3-substituted pyrazoles have been achieved using K₂CO₃-DMSO. The regioselectivity is justified by the DFT calculations at the B3LYP/6-31G??(d) level. A consistent steric effect on chemical shift has been observed for N-alkyl pyrazole analogues. Twenty-five X-ray crystallographic structures have been obtained to confirm the regiochemistry of the major products.