Efficient Regioselective Iodination of Pyrazole Derivatives Mediated by Cadmium(II) Acetate

Abstract

The present study focuses on the iodination of pyrazoles mediated by cadmium (II) acetate. The objects of research were compounds with pyrazole rings substituted by N-propargyl, C, N-alkyl groups. Depending on the molar ratios of the reagents effective ways of obtaining mono- and triiodo-substituted products with the participation of the propargylic fragment in DMSO were elucidated. Induced by the cadmium (II) acetate principles of electrophilic iodination of the C-4 position of the pyrazole ring containing electron-donating groups were revealed. The iodination of the pyrazole derivative with only propargylic substituent was found to target the CH-acidic center of the triple bond and to lead to the corresponding iodoalkyne. An iodo-substituted product with triple bond is more reactive and prone to further electrophilic iodination forming a triiodo-substituted derivative. The introduction of methyl groups in the pyrazole ring of derivatives with propargylic substituent contributed to the promotion of competitive iodination reactions due to the increase in nucleophilicity of the pyrazole ring. Dimerized pyrazole rings with carbon atoms in the 4-th position did not succeed in being iodinated by the mentioned way. Possible pathways for both triple bond and pyrazole ring iodination involving acetyl hypoiodite were proposed.