Development of an Efficient Synthetic Process for Broflanilide

Abstract

This article describes the development of an efficient and scalable synthetic route to the novel insecticide broflanilide (1). This redesigned synthetic sequence starts from 2-fluoro-3-nitrobenzoic acid and 4-(perfluoropropan-2-yl)-2-(trifluoromethyl) aniline and provides the target product in a high overall yield through condensation, nitro group reduction, N-methylation, amidation, and subsequent bromination steps. The desired amide moiety is established under mild conditions, and imide generation is avoided. Using paraformaldehyde and Pt/C for N-methylation and NaBr-NaClO for bromination increased the industrial suitability of this route. Unlike existing routes, this new route requires isolation at only six steps (including the heptafluorination), and the overall yield was 60.3%, representing a significant improvement. Broflanilide (1) crystals were obtained from recrystallization in 98% aqueous CH3OH, and the structure was confirmed by X-ray analysis. This work provides a reliable strategy for the large-scale manufacturing of broflanilide (1).

Bromide Oxidation: A Safe Strategy for Electrophilic Brominations

“…Advantages of this method are, as mentioned before, the low cost and lower hazard of NaOCl, and the simplicity of the reaction [9a,26b,27a] . Additionally, while NaOCl is strong enough to oxidise bromide, it is not a very strong oxidant.…”

“…To the best of our knowledge, bromine, hypobromous acid or hypobromite generated in situ from NaOCl have the same reactivity as standard bromine starting product [26] . NaOCl has been used to brominate arenes [26b,27] and double bonds [9a,b,10,28] . It also has been used to regenerate organic ammonium tribromides from the corresponding bromide salt [29] .…”

Design, Synthesis, and Insecticidal and Fungicidal Activities of Ether/Oxime-ether Containing Isoxazoline Derivatives

“…The use of agricultural insecticides has greatly reduced the damage caused by pests . However, with the widespread use of insecticides, insect resistance and harm to the environment and human health have become more and more obvious . For example, cyclopentadiene, phenylpyrazole, and macrolide insecticides, which are agents targeting GABA receptors, have been restricted for use due to various existing factors and problems. − …”

Visible-Light-Induced Metal-Free Decarboxylative Perfluoroalkylation of Aryl Acrylic Acids

“…17 5c) is an important intermediate in the synthesis of broflanilide. 18 Herein, we realized the efficient one-pot two-steps synthesis of intermediate with our method (68%) (Scheme 3) (see the Supporting Information for experimental procedure).…”

“…Broflanilide is a novel pesticide which has distinctive mode of action from traditional γ-aminobutyric acid receptor (GABAR) inhibitor . 2-Fluoro-3-nitro- N -(4-(perfluoropropan-2-yl)-2-(trifluoromethyl)­phenyl)­benzamide ( 5c ) is an important intermediate in the synthesis of broflanilide . Herein, we realized the efficient one-pot two-steps synthesis of intermediate with our method (68%) (Scheme ) (see the Supporting Information for experimental procedure).…”