Kinetic study of 2-butanol O-acylation and sec-butylamine N-acylation catalyzed by Candida antarctica lipase B

Abstract

The aim of this work was to study the differential behavior shown by Candida antarctica lipase B during the O-acylation and N-acylation of monofunctional alcohols and monofunctional amines. To achieve this, 2-butanol and sec-butylamine were used as model molecules. Yields, kinetics and enantioselectivity were studied for both reactions. Although a steady-state ordered ternary complex bi-bi mechanism was obtained for the O-acylation of 2butanol, a ping-pong bi-bi mechanism was obtained for the N-acylation in case of low secbutylamine concentrations. The values of apparent kinetics parameters were calculated: the enantiomeric ratios (E) were evaluated and confirmed the preference of Candida antarctica lipase B for the (R)-enantiomer, which was consistent with the literature. The enantioselectivity was calculated for the alcohol (E ≈ 3.17) and for the amine (E ≈ 1.34). Concerning the O-acylation, the yields were found to be very similar for both enantiomers R and S. However, both initial rates and yields of the (R)-enantiomer N-acylation were higher than those of the (S)-enantiomer. In the last part of our study, the chemoselectivity of Candida antarctica lipase B was evaluated, showing that Candida antarctica lipase B was a chemoselective enzyme that preferentially catalyzed the O-acylation to the detriment of the N-acylation (C ≈ 92, for the selective acylation of (R)-enantiomers). These results provide new insights for the synthesis of products issued from the selective acylation of multifunctional substrates such as amino-alcohols.

Catalytic amide formation from non-activated carboxylic acids and amines

“…This reaction has been considered 35 challenging due to the competing acid-base reaction, which occurs when the amine and the carboxylic acid are mixed. Although the amide bond can be formed from the corresponding ammonium carboxylate salt upon heating, this reaction has generally been considered to be of limited preparative value.…”

“…15 The literature on thermal amidation is not covered in this review unless the non-catalysed reaction is specifically mentioned by the 30 authors. 35 …”

“…Not too surprisingly, the diacylated product was favoured by an excess of the fatty acid; a 2-4 molar excess of the carboxylic acid gave rise to 70-90% yield of the N,O-diacylated product. Additional studies by Fernandez-Perez and Otero on secondary amines concluded that an excess of diethanolamine resulted in 35 full chemoselectivity in favour of the tertiary amide product. 38 It was also found that the monoacylated ester was a rapidly formed intermediate in dioxane, which subsequently was transformed into the thermodynamically more stable amide.…”

“…Rhizopus arrhizus lipase-catalysed amidation of 35 carboxylic acids of different chain lengths (Tuccio, 1991).…”

“…34 The mechanism and origin of selectivity of the immobilized CAL-B was investigated, as well as the kinetics of O-vs N-acylation of 105 myristic acid with 2-butanol and sec-butylamine. 35 The catalytic amidation of ethanolamine with fatty acids was studied by Fernandez-Perez and Otero. It was found that high yields (90-94%) of the amide surfactants could be obtained using Novozym® 435 as amidation catalyst.…”