Synthesis of Boscalidviaa three-step telescoped continuous flow process implemented on a MJOD reactor platform

Abstract

A three step continuous/semi-flow process leading to the fungicide Boscalid® is disclosed.

A Sustainable 1-Pot, 3-Step Synthesis of Boscalid Using Part per Million Level Pd Catalysis in Water

“…In the patented route by the BASF, although complete details about the process are lacking, the sequence involved (1) a Pd(0)-catalyzed Suzuki–Miyaura (SM) coupling, (2) reduction of the nitrobiaryl intermediate, and (3) an amide bond construction. A few new routes have appeared recently, including one utilizing flow chemistry; however, all involve use of organic solvents, high catalyst loadings, and especially high temperatures. Moreover, selective nitro group reduction in the presence of an aryl chloride required expensive Pt/C under high pressure of hydrogen. , Dunst and Knochel used an alternative approach to replace the Suzuki–Miyaura (SM) reaction by a Kumada-type coupling leading to the desired biarylamine in 70% yield with 1 mol % of a Pd catalyst .…”

“…A few new routes have appeared recently, including one utilizing flow chemistry; however, all involve use of organic solvents, high catalyst loadings, and especially high temperatures. Moreover, selective nitro group reduction in the presence of an aryl chloride required expensive Pt/C under high pressure of hydrogen. , Dunst and Knochel used an alternative approach to replace the Suzuki–Miyaura (SM) reaction by a Kumada-type coupling leading to the desired biarylamine in 70% yield with 1 mol % of a Pd catalyst . In short, none of these methods offer an environmentally sustainable, benign approach.…”

Synthesis and process optimization of Boscalid by catalyst Pd-PEPPSI-IPrDtBu-An

“…Schwarze et al 15 reported an environmentally friendly solvents for synthesis of Boscalid, the Suzuki reaction was catalyzed by watersoluble homogeneous Pd/SPhos, together with an easily recyclable heterogeneous PtIr@TiO 2 , the condensation reaction under the conditions of triethylamine, the catalysts used are not easily available. Audun Drageset et al 16 reported a three step continuous/semi-flow process for synthesis of Boscalid, the Suzuki coupling reaction was catalyzed by Pd(PPh 3 ) 4 , the reduction reaction was used of NaBH 4 /CoSO 4 .…”

A Comment on Continuous Flow Technologies within the Agrochemical Industry

“…Recently, using a similar reaction sequence adapted to run on a multijet oscillating disk (MJOD) continuous flow reactor platform, a group at the University of Bergen in Norway reported the production of boscalid at a rate of around 8.4 g/h in 42% overall yield for the three steps. 23 In that route, a lowertemperature (80 °C) Suzuki−Miyaura coupling was used, which was followed by a cobalt boride reduction step to efficiently convert the nitro group to the required amine substituent. The final coupling was achieved through the in situ formation of an iminosulfanone using SOCl 2 followed by condensation with 2-chloropyridine-3-carboxylic acid.…”