Substituent Effects on the Crystal Structures of Salts Prepared from (R)-2-Methoxy-2-(1-naphthyl)propanoic Acid and (R)-1-Arylethylamines

Akio Ichikawa,Yuji Mikata,Hiroshi Ono

doi:10.3390/cryst7090263

Abstract

The crystal structures of salts 6–9 prepared from (R)-2-methoxy-2-(1-naphthyl)propanoic acid [(R)-MαNP acid, (R)-1] and (R)-1-arylethylamines [salt 6, (R)-1-(4-methoxyphenyl)ethylamine∙(R)-1; salt 7, (R)-1-(4-fluorophenyl)ethylamine∙(R)-1; salt 8, (R)-1-(4-chlorophenyl)ethylamine∙(R)-1; and salt 9, (R)-1-(3-chlorophenyl)ethylamine∙(R)-1] were elucidated by X-ray crystallography. The solid-state associations and conformations of the MαNP salts were defined using the concepts of supramolecular- and planar chirality, respectively, and the crystal structures of salts 6–9 were interpreted as a three-step hierarchical assembly. The para-substituents of the (R)-1-arylethylammonium cations were found on sheet structures consisting of 21 columns. Thus, salts possessing smaller para-substituents, that is, salt 7 (p-F) and salt 9 (p-H), and larger para-substituents, that is, salt 6 (p-OMe) and salt 8 (p-Cl), crystallized in the space groups P21 and C2, respectively. Additionally, weak intermolecular interactions, that is, aromatic C–H···π, C–H···F, and C–H···O interactions, were examined in crystalline salts 6–9.

Highlights

Stereochemistry is important in biofunctional molecules [1]
In 2011, we examined the crystal structures of the less-soluble salt 4 [(R)-3·(R)-1] and the more-soluble diastereomeric salt (R)-3·(S)-1 by X-ray crystallography [6]
Results have shown that intercolumnar aromatic C–H···π interactions [7,8,9] are more effective with the less-soluble salt 4

Summary

Introduction

Stereochemistry is important in biofunctional molecules [1]. methods that facilitate the elucidation of absolute configurations and the preparation of single enantiomers are highly desired [2]. Based on stereochemical studies of biofunctional molecules, we synthesized a chiral resolving agent, MαNP acid (acid 1, Figure 1) [3,4]. In 2011, we examined the crystal structures of the less-soluble salt 4 [(R)-3·(R)-1] and the more-soluble diastereomeric salt (R)-3·(S)-1 by X-ray crystallography [6]. Those crystal structures revealed a chiral recognition mechanism during the enantioresolution process. With the less-soluble salt 4, the (R)-MαNP anion and the (R)-PEA cation form a close ion-pair via a methoxy-group-assisted salt bridge and aromatic C–H···π interactions (Figure 2A). The close ion-pairs join with the salt bridges to form 21 columns. Results have shown that intercolumnar aromatic C–H···π interactions [7,8,9] are more effective with the less-soluble salt 4

Methods

Results

Conclusion