Lipase-catalyzed kinetic resolution of (±)-mandelonitrile under conventional condition and microwave irradiation

Abstract

A resolução cinética da (±)-mandelonitrila foi realizada utilizando a lipase de Candida antarctica sob condição convencional (agitação orbital) e irradiação de micro-ondas em tolueno, produzindo o acetato de (S)-mandelonitrila com elevada seletividade (92-98% ee, excesso enantiomérico). O álcool remanescente da (R)-mandelonitrila sob irradiação de micro-ondas e agitação orbital foi parcialmente convertido em benzaldeído via equilíbrio químico espontâneo. O acetato de (S)-mandelonitrila foi produzido com 92% ee e rendimento de 35% em 8 h de reação sobre irradiação de micro-ondas. A transesterificação da (±)-mandelonitrila em agitador orbital produziu a (R)-mandelonitrila (51% ee) remanescente e o acetato da (S)-mandelonitrila (98% ee) de acordo com a regra Kazlauskas com 184 h de reação.The kinetic resolution of (±)-mandelonitrile was carried out using lipase from Candida antarctica under conventional condition (orbital shaker) and microwave irradiation in toluene, producing the (S)-mandelonitrile acetate with high selectivity (up to > 98% ee, enantiomeric excess). The unreacted (R)-mandelonitrile under microwave irradiation and conventional condition was partially converted into benzaldehyde by spontaneous chemical equilibrium. The (S)-mandelonitrile acetate under microwave irradiation was produced with 92% ee and 35% yield for 8 h of reaction. Conventional transesterification of (±)-mandelonitrile in an orbital shaker produced unreacted (R)-mandelonitrile (51% ee) and (S)-mandelonitrile acetate (98% ee) in accordance with Kazlauskas rule for 184 h of reaction.

One-Dimensional 13C NMR Is a Simple and Highly Quantitative Method for Enantiodiscrimination

“…Several high-performance liquid chromatography (HPLC) methods have been described in which different types of chiral stationary phases (CSPs) are used: Chiralcel OB-H [ 18 ], Chiralcel OJ-H [ 19 , 20 , 21 , 22 ], Sumichiral OA-4400 [ 23 ], Chiralpak IA [ 24 ] and Chiralcel OD-H [ 25 ]. These stationary phases were used in combination with either mixtures of n-hexane and isopropanol [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], n-hexane, ethanol and 1,2-dichloroethane [ 23 ], or n-hexane, isopropanol and trifluoroacetic acid [ 24 ]. By means of these chiral HPLC methods, enantiomeric excess values of mandelonitrile up to 99% could be established [ 18 , 20 ].…”

Chemoenzymatic resolution of fluorinated compounds by lipase CALB under microwave irradiation

“…Chemoenzymatic resolution yielded the (S)-4 with better enantioselectivity and conversion in orbital shaker (48 h, c=49%, >99% ee) and microwave irradiation (14 h, c=49%, 98% ee). In the literature, excellent results have been reported by us using microwave irradiation in chemoenzymatic reactions of fluorinated compounds 3,4 . Scheme 1 …”

The influence of conventional heating and microwave irradiation on the resolution of (RS)-sec-butylamine catalyzed by free or immobilized lipases

“…[12][13][14][15][16][17] Besides, in some enzymatic reactions the selectivity, such as stereoselectivity or regioselectivity, are clearly influenced. [17][18][19] Yu et al 18 observed that MW irradiation increased both the activity and enantioselectivity of novozym 435, and also the thermal stability and reusability in the resolution of (RS)-2-octanol with vinyl acetate as the acyl donor. A conversion of 50% was achieved in a 3 h reaction under MW irradiation while around 12 h was required to obtain the same conversion under conventional heating.…”

“…In both conditions, the (S)-mandelonitrile acetate was obtained with high selectivity (ee of 92-98%). 19 However, most enzymes are deactivated by the fast increase in temperature under MW irradiation. 18 This problem may be solved by the use of immobilized enzymes which, in general, exhibit higher thermal stability than the free form.…”