Hosseinalipour Mercedeh Sadat, Deck Leif-Thore, Mazzotti Marco
Institute of Energy and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland.
Cryst Growth Des. 2024 Apr 23;24(9):3925-3932. doi: 10.1021/acs.cgd.4c00233. eCollection 2024 May 1.
Temperature cycling represents an effective means for the deracemization of chiral compounds that crystallize as conglomerates and racemize in solution. In such a process, a suspension enriched in the desired enantiomer is converted into an enantiopure one through periodic cycles of crystal dissolution and crystal growth. We show that performing temperature cycling at higher temperatures leads to faster deracemization and, consequently, higher productivity. However, this comes at the cost of lower recovery, as the solution contains potentially relevant amounts of solute due to the higher solubility at an elevated temperature. In this work, we introduce and compare two process variants that mitigate this issue. The first involves temperature cycling, followed by linear cooling, whereas the second is based on merging the temperature cycles and cooling crystallization. Experiments carried out with the chiral compound -(2-methylbenzylidene)-phenylglycine amide show that the former variant is faster than the latter, and it is easier to design and implement. In this process, the choice of an appropriate cooling rate is essential to avoid nucleation of the undesired enantiomer.
温度循环是一种有效的外消旋化手段，适用于以聚集体形式结晶并在溶液中发生消旋的手性化合物。在这样一个过程中，富含所需对映体的悬浮液通过晶体溶解和晶体生长的周期性循环转化为对映体纯的悬浮液。我们表明，在较高温度下进行温度循环会导致更快的外消旋化，从而提高生产率。然而，这是以较低的回收率为代价的，因为在较高温度下溶解度较高，溶液中含有潜在的大量溶质。在这项工作中，我们介绍并比较了两种缓解此问题的工艺变体。第一种方法是温度循环，然后线性冷却，而第二种方法是基于合并温度循环和冷却结晶。用手性化合物-(2-甲基亚苄基)-苯甘氨酸酰胺进行的实验表明，前一种变体比后一种变体更快，并且更容易设计和实施。在这个过程中，选择合适的冷却速率对于避免不需要的对映体成核至关重要。
