Development of a Trimethylamine-Catalyzed Novel Synthesis of Azoxystrobin

Abstract

We report the development of a novel method for the synthesis of Azoxystrobin, which employs trimethylamine as a catalyst. This appealing catalytic system offers several advantages, including low cost, excellent reactivity, easy recovery, and the ability to be used repeatedly with minimal environmental impact. Mechanistic studies and density functional theory (DFT) calculations suggest that the involvement of a highly active quaternary ammonium salt intermediate is likely responsible for the efficient catalysis. This can be attributed to the low steric hindrance, flexible bare nature of the lone pair of electrons on the nitrogen atom, and low activation energy barrier of trimethylamine. These findings hold great promise for the mass production of Azoxystrobin.

2-(1-Methoxycarbonyl-2-phenyleth-1-yl)-1-benzylpyridin-1-ium Bromide

“…Within organic chemistry, ammonium cations are widely present in structures of phase-transfer compounds [1] (for instance, tetrabutylammonium bromide), drugs (neuromuscular-blocking drugs, cholinergic drugs, antimicrobials [2]), surfactants (phosphatidylcholines) and many others. In synthesis, due to their electrophilic nature, quaternary ammonium cations are also exploited as leaving groups in nucleophilic substitutions [3,4]. The most common method of synthesizing quaternary pyridinium or ammonium salts is the Menšutkin reaction, i.e., simple alkylation with alkyl halides, which often requires heat [5][6][7].…”