Complete deracemization by attrition-enhanced Ostwald ripening elucidated
Complete deracemization by attrition-enhanced Ostwald ripening elucidated
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DOI：
10.1002/anie.200801846
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Vlieg, Elias
中科院分区：
文献类型：
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作者：
Noorduin, Wim L.;Meekes, Hugo;Vlieg, Elias
通过晶种或加入特制添加剂诱导外消旋混合物结晶的直接拆分构成了使用非对映异构体盐分离的有吸引力的替代方案。[1-4]不幸的是，在单一拆分步骤中的产率低，并且每种对映异构体的总产率限于50%。直接拆分与溶液中的外消旋作用相结合，可实现对映体的完全转化。[5-14]在一次操作中完全解决问题将具有很大的实际用途，但实例有限。最近，维埃德马已经证明了一个本质上的非手性分子，氯酸钠，通过研磨的总分辨率。[15受维埃德马的启发，[15]用手性氨基酸衍生物的固相与发生外消旋的溶液接触来证明原理;这在研磨时平稳地演变为单一手性固体终态。[17]这在N-（2-甲基亚苄基）-苯基甘氨酸酰胺（1）的聚集体中得到了证实（方案1）。以固相中略微富集一种对映异构体的混合物开始该方法，固相通过溶液相外消旋反应完全转化为主要对映异构体。在几周内，可以定量地获得任一固体对映体，ee> 99.9%。蒙特卡罗模拟得出的模型表明，两个过程是导致去消旋化的原因：晶体的持续磨损和奥斯特瓦尔德熟化，这导致以较小晶体为代价生长大晶体。[18-20]在这里，我们探讨这种去种族化的参数
Direct resolution by crystallization of racemic mixtures, induced by seeding or by adding tailor-made additives, constitutes an attractive alternative to separation using diastereomeric salts.[1–4] Unfortunately, the yield in a single resolution step is low and the overall yield limited to 50% of each enantiomer. Combination of a direct resolution with racemization in the solution permits a total enantiomeric transformation.[5–14] Complete resolution in a single operation would be of great practical use but examples have been limited. Recently, Viedma has demonstrated the total resolution of an intrinsically achiral molecule, NaClO3, by means of abrasive grinding.[15, 16]Inspired by Viedma,[15] proof of principle was given with a solid phase of a chiral amino acid derivative in contact with a solution in which racemization occurs; this evolved smoothly to a single chiral solid end state on abrasive grinding.[17] This was demonstrated for the conglomerate N-(2-methylbenzylidene)-phenylglycine amide (1)(Scheme1). Starting the process with a mixture slightly enriched in one enantiomer in the solid phase, the solid phase is completely converted into the major enantiomer through the solution-phase racemization reaction. Within a few weeks either solid enantiomer can be obtained quantitatively with ee> 99.9%. Monte Carlo simulations led to a model that showed that two processes are responsible for the deracemization: continuous attrition of crystals and Ostwald ripening, which leads to growth of large crystals at the cost of smaller ones.[18–20] Here we explore the parameters of this deracemization