Murali Chebrolu, Shashidhar Mysore S, Gonnade Rajesh G, Bhadbhade Mohan M
Division of Organic Chemistry, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411 008, India.
Chemistry. 2009;15(1):261-9. doi: 10.1002/chem.200801484.
Racemic 2,4-di-O-benzoyl-myo-inositol-1,3,5-orthoacetate, which normally crystallizes in a monoclinic form (form I, space group P2(1)/n) could be persuaded to crystallize out as a metastable polymorph (form II, space group C2/c) by using a small amount of either D- or L- 2,4-di-O-benzoyl-myo-inositol-1,3,5-orthoformate as an additive in the crystallization medium. The structurally similar enantiomeric additive was chosen by the scrutiny of previous experimental results on the crystallization of racemic 2,4-di-O-benzoyl-myo-inositol-1,3,5-orthoacetate. Form II crystals can be thermally transformed to form I crystals at about 145 degrees C. The relative organization of the molecules in these dimorphs vary slightly in terms of the helical assembly of molecules, that is, electrophile (El)...nucleophile (Nu) and C-H...pi interactions, but these minor variations have a profound effect on the facility and specificity of benzoyl-group-transfer reactivity in the two crystal forms. While form II crystals undergo a clean intermolecular benzoyl-group-transfer reaction, form I crystals are less reactive and undergo non-specific benzoyl-group transfer leading to a mixture of products. The role played by the additive in fine-tuning small changes that are required in the molecular packing opens up the possibility of creating new polymorphs that show varied physical and chemical properties. Crystals of D-2,6-di-O-benzoyl-myo-inositol-1,3,5-orthoformate (additive) did not show facile benzoyl-group-transfer reactivity (in contrast to the corresponding racemic compound) due to the lack of proper juxtaposition and assembly of molecules.
外消旋2,4 - 二 - O - 苯甲酰基 - 肌醇 - 1,3,5 - 原乙酸酯通常以单斜晶形式（晶型I，空间群P2(1)/n）结晶，通过在结晶介质中使用少量D - 或L - 2,4 - 二 - O - 苯甲酰基 - 肌醇 - 1,3,5 - 原甲酸酯作为添加剂，可以促使其以亚稳多晶型（晶型II，空间群C2/c）结晶析出。通过对先前关于外消旋2,4 - 二 - O - 苯甲酰基 - 肌醇 - 1,3,5 - 原乙酸酯结晶的实验结果进行仔细研究，选择了结构相似的对映体添加剂。晶型II晶体在约145℃时可热转变为晶型I晶体。这些双晶型中分子的相对排列在分子的螺旋组装方面略有不同，即亲电体（El）...亲核体（Nu）和C - H...π相互作用，但这些微小差异对两种晶型中苯甲酰基转移反应的难易程度和特异性有深远影响。虽然晶型II晶体发生清晰的分子间苯甲酰基转移反应，但晶型I晶体反应性较低，发生非特异性苯甲酰基转移，导致产物混合物。添加剂在微调分子堆积所需的微小变化中所起的作用，为创造具有不同物理和化学性质的新多晶型物开辟了可能性。D - 2,6 - 二 - O - 苯甲酰基 - 肌醇 - 1,3,5 - 原甲酸酯（添加剂）的晶体由于分子缺乏适当的并置和组装，未表现出容易的苯甲酰基转移反应性（与相应的外消旋化合物相反）。
