In Situ Separation of the Chiral Target Compound (S)-2-Pentanol in Biocatalytic Reactive Distillation
In Situ Separation of the Chiral Target Compound (S)-2-Pentanol in Biocatalytic Reactive Distillation
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DOI：
10.1021/acs.iecr.7b01163
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发表时间：
2017-06-07
影响因子：
4.2
通讯作者：
Liese, Andreas
中科院分区：
文献类型：
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作者：
Kuehn, Steffen;Sluyter, Gerrit;Liese, Andreas
首次实现了手性目标化合物作为集成生物催化间歇反应蒸馏塔顶部馏出物的原位分离。应用的反应体系是在固定化南极假丝酵母脂肪酶 B (Novozym435) 的催化下，与丁酸丙酯发生酯交换反应，进行 (R/S)-2-戊醇的外消旋拆分。生物催化剂集成在作为塔内件的金属丝网催化填料篮中实现。通过低沸点丙醇和目标化合物(S)-2-戊醇的分馏，平衡限制反应转移至产物侧。 (S)-2-戊醇的摩尔分数增加至 x(S)-2-PeOH = 65 +/- 4%，对映体过量 90 +/- 4%，总转化率达到 51 +/- 3%。在我们的预选工具中研究了反应系统的可行性。该工具的开发目的是根据有关生物催化剂稳定性和反应物之间沸点差异的标准来评估酯交换反应塔设置中的预定义操作条件。随后选定的(R/S)-2-戊醇与丁酸丙酯的反应在间歇反应蒸馏塔中成功进行，并原位分离了我们的目标化合物(S)-2-戊醇。与文献中当前的例子相比，这清楚地证明了应用生物催化反应蒸馏在手性合成中一锅式目标化合物分离的可能性。
In situ separation of a chiral target compound is realized for the first time as distillate on top of an integrated biocatalytic batch reactive distillation column. The applied reaction system is the racemic resolution of (R/S)-2-pentanol in a transesterification with propyl butyrate, which is catalyzed by immobilized Candida antarctica lipase B (Novozym435). Biocatalyst integration is realized in baskets of wire gauze catalytic packings as column internals. The equilibrium limited reaction is shifted to the product side by fractional distillation of low boiling propanol and the target compound (S)-2-pentanol. Increased molar fractions up to x(S)-2-PeOH = 65 +/- 4% with an enantiomeric excess of 90 +/- 4% and 51 +/- 3% overall conversion are reached for (S)-2-pentanol. Feasibility of the reaction system is investigated in our preselection tool. This tool is developed to evaluate predefined operation conditions in the column setup for transesterification reactions based on criteria regarding biocatalyst stability and boiling point differences between the reactants. The subsequently selected reaction of (R/S)-2-pentanol with propyl butyrate is successfully carried out in a batch reactive distillation column with in situ separation of our target compound (S)-2-pentanol. In contrast to current examples in the literature, this clearly demonstrates the possibility of one-pot target compound isolation within chiral synthesis applying biocatalytic reactive distillation.