Candida antartica lipase B catalyzed polycaprolactone synthesis:: Effects of organic media and temperature

Engineering of the reaction medium and study of an expanded range of reaction temperatures were carried out in an effort to positively influence the outcome of Novozyme-435 (immobilized Lipase B from Candida antarctica) catalyzed epsilon -CL polymerizations. A series of solvents including acetonitrile, dioxane, tetrahydrofuran, chloroform, butyl ether, isopropyl ether, isooctane, and toluene (log P from -1.1 to 4.5) were evaluated at 70 degreesC. Statistically (ANOVA), two significant regions were observed. Solvents having log P values from -1.1 to 0.49 showed low propagation rates (less than or equal to 30% epsilon -CL conversion in 4 h) and gave products of short chain length (M-n less than or equal to 5200 g/mol). In contrast, solvents with log P values from 1.9 to 4.5 showed enhanced propagation rates and afforded polymers of higher molecular weight (M-n = 11500-17000 g/mol). Toluene, a preferred solvent for this work, was studied at epsilon -CL to toluene (wt/vol) ratios from 1:1 to 10:1. The ratio 1.2 was selected since, for polymerizations at 70 degreesC, 0.3 mL of epsilon -CL and 4 h, gave high monomer conversions and M-n values (similar to 85% and similar to 17 000 g/mol, respectively). Increasing the scale of the reaction from 0.3 to 10 mt of CL resulted in a similar isolated product yield, but the M-n increased from 17 200 to 44 800 g/mol. Toluene appeared to help stabilize Novozyme-435 so that lipase-catalyzed polymerizations could be conducted effectively at 90 degreesC. For example, within only 2 h at 90 degreesC (toluene-d(8) to epsilon -CL, 5:1, similar to1% protein), the % monomer conversion reached similar to 90%. Also, the controlled character of these polymerizations as a function of reaction temperature was evaluated.