Studies toward an Improved Process for N⁴,N⁴-Disubstituted-2-cyano-N¹,N¹-dimethyl-1H-imidazole-1,4-disulfonamides

Abstract

The development of a practical and cost-effective process for the manufacture of the title fungicidal compounds is described. In particular, substantial improvements in the chlorosulfonation of imidazole, studies on the stability of various cyanating agents, and a novel formylation/oximation/dehydration sequence to introduce the 2-cyano group are described.

Design and Synthesis of an Fmoc-SPPS-Compatible Amino Acid Building Block Mimicking the Transition State of Phosphohistidine Phosphatase

“…The synthesis (Scheme ) commenced by heating imidazole ( 2 ) in chlorosulfonic acid. Subsequent addition of thionyl chloride yielded 4(5)-imidazolesulfonyl chloride ( 3 ) in 62% after aqueous workup . Reaction of 3 with N , N -bis(2,4-dimethoxybenzyl)amine (DMB 2 NH) in the presence of DIPEA in DCM at 0 °C resulted in sulfonamide 4 in high yield (90%).…”

Synthesis and Chemistry of 4,5-Dimagnesioimidazole Dianions

“…The generation of imidazolyl carbanions, either by metal−halogen exchange or by direct metalation, followed by their reaction with electrophiles provides a powerful method for the synthesis of functionalized imidazoles . For example, fungicidally active cyanoimidazoles, the antitumor agent carmethizole, the α 2 -adrenergic agonist medetomidine, and the histamine H 3 antagonist thioperamide have all been efficiently prepared using imidazolyl anion chemistry. Most synthetic examples have utilized imidazolyl monoanions, but dianions are also known.…”