The enzymatic resolution of 1‐(4‐chlorophenyl)ethylamine by Novozym 435 to prepare a novel triazolopyrimidine herbicide

Abstract

The kinetic resolution of (R,S)‐1‐(4‐chlorophenyl)ethylamine was accomplished using a commercial lipase from Candida antarctica (Novozym 435). The performance of this lipase was investigated for the enantioselective amidation of (R,S)‐1‐(4‐chlorophenyl)ethylamine, leaving the target product (S)‐1‐(4‐chlorophenyl)ethylamine in its unreacted form. The effects of various types of solvents and an acyl donor, the molar ratio of the substrate to the acyl donor, and the reaction temperature were studied. The optimum reaction conditions were found to result in amidation with methyl 2‐tetrahydrofuroate at 40°C in methyl tert‐butyl ether, with a substrate/acyl donor molar ratio of 1:2.4. The conversion rate of (R,S)‐1‐(4‐chlorophenyl)ethylamine was 52%, with an enantiomeric excess of 99% towards the unreacted substrate in a reaction time of 22 hours. Finally, using optically pure (S)‐1‐(4‐chlorophenyl)ethylamine as the raw material, the chemical synthesis of (S)‐N‐(1‐(4‐chlorphenyl)ethyl)‐2‐(5,7‐dimethyl‐[1,2,4]triazolo[1,5‐a]pyrimidin‐2‐ylthio)acetamide, a novel triazolopyrimidine herbicide, was achieved, and the total yield and purity were 83.5% and 95.3%, respectively.

Novozym 435: the “perfect” lipase immobilized biocatalyst?

“…319 The resolution of (R,S)-1-(4-chlorophenyl)ethylamine was achieved employing N435. 320 The target unreacted product (S)-1-(4chlorophenyl)ethylamine was obtained with an ee of 99% after a conversion of 52%. N435 was used as an example of the use of CO 2 -expanded bio-based liquids.…”

Immobilization of lipases on hydrophobic supports: immobilization mechanism, advantages, problems, and solutions

“…As a clear example of the simplicity and usefulness of this immobilization protocol, Novozym 435, that is the immobilized form of the lipase B from Candida antarctica and very likely the most utilized commercial immobilized biocatalysts, has been prepared using this strategy employing Lewatit VP OC 1600 as support (Bansode et al, 2017;Du et al, 2004;Endo et al, 2018;Galgali et al, 2018;Kaar et al, 2003;Ortiz et al, 2019;Polloni et al, 2017;Sbardelotto et al, 2018;Zhang et al, 2018). Table 1 shows a compilation of the most utilized hydrophobic supports and the lipases that have been immobilized on them (from 2010 until present).…”

New Advances in the Synthetic Application of Enantiomeric 1-Phenylethylamine (α-PEA): Privileged Chiral Inducer and Auxiliary

“…Recently, for the synthesis of ring-substituted, optically active isomers of 1-phenylethylamines, the chemo-enzymatic method has also been developed [ 11 ]. The method is particularly attractive because of the commercial availability of the immobilized enzymes.…”

“…The method is particularly attractive because of the commercial availability of the immobilized enzymes. Thus, for ( S )-1-(4-chlorophenyl)ethylamine, a key intermediate for the synthesis of the corresponding acetamide (a herbicide), the resolution catalyzed by the immobilized lipase (Novozym 435) was chosen ( Scheme 3 ) [ 11 ].…”