Remarkable Similarity of Molecular Packing in Crystals of Racemic and Enantiopure 2-Phenylpropionamide: Z′ = 4 Structures, Molecular Disorder, and the Formation of a Partial Solid Solution,Crystal Growth & Design

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Remarkable Similarity of Molecular Packing in Crystals of Racemic and Enantiopure 2-Phenylpropionamide: Z′ = 4 Structures, Molecular Disorder, and the Formation of a Partial Solid Solution
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2022-06-27 , DOI: 10.1021/acs.cgd.2c00509
Raúl Castañeda ₁ , Sergei V Lindeman ₂ , Arcadius V Krivoshein ₁ , Alejandro J Metta-Magaña ₃ , Yongli Chen ₄ , Tatiana V Timofeeva ₁

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Substituted acetamides (many of which are chiral) are known to be pharmacologically active. 2-Phenylpropionamide (2PPA) is one of the simplest chiral α-substituted acetamides and thus is of interest as a model compound in the growth and design of pharmaceutical crystals. In this study, the crystal structures of racemic and enantiopure forms of 2PPA were determined for the first time using single-crystal X-ray diffraction at 100 K. The relationship between the signs of optical rotation and the absolute configurations is (+)-(S)-2PPA and (−)-(R)-2PPA. Four symmetrically independent molecules with different conformations are observed in crystals of both racemic and enantiopure forms. Remarkably, all forms adopt very similar supramolecular structures, H-bonded corrugated layers, that can be described using a R₂²(8)R₆⁴(16) graph set. The outer surfaces of these layers are built of nonpolar phenyl groups, and their inner structures are composed of H-bonded amide groups. The presence of these layers determines the thin plate shape of 2PPA crystals. Spectroscopically, the racemic and enantiopure forms substantially differ only in the low-frequency Raman region. X-ray diffraction data suggest that the racemic form of 2PPA is a partial solid solution made possible by statistical occupancy of molecular positions by (R)- and (S)-enantiomers.

中文翻译：

外消旋和对映体纯 2-苯基丙酰胺晶体中分子堆积的显着相似性：Z′ = 4 结构、分子无序和部分固溶体的形成

已知取代的乙酰胺（其中许多是手性的）具有药理学活性。 2-苯基丙酰胺 (2PPA) 是最简单的手性 α-取代乙酰胺之一，因此作为药物晶体生长和设计中的模型化合物受到关注。本研究首次利用100 K单晶X射线衍射测定了2PPA的外消旋体和对映体纯体的晶体结构。旋光符号与绝对构型之间的关系为(+)-( S )-2PPA 和 (−)-( R )-2PPA。在外消旋和对映体纯形式的晶体中观察到四个具有不同构象的对称独立分子。值得注意的是，所有形式都采用非常相似的超分子结构，即 H 键合波纹层，可以使用R ₂ ² (8) R ₆ ⁴ (16) 图形集进行描述。这些层的外表面由非极性苯基构成，其内部结构由氢键酰胺基组成。这些层的存在决定了 2PPA 晶体的薄板形状。从光谱上看，外消旋和对映体纯形式仅在低频拉曼区域存在显着差异。 X 射线衍射数据表明，2PPA 的外消旋形式是部分固溶体，通过 ( R )- 和 ( S )- 对映异构体对分子位置的统计占据而成为可能。

更新日期：2022-06-27

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