CRYSTAL GROWTH & DESIGN
Polymorphs of a Cocrystal with Achiral and Chiral Structures Prepared by Pseudoseeding: Tryptamine/ Hydrocinnamic Acid
2001 VOL. 1, NO. 5 355-357
Hideko Koshima* and Masashi Miyauchi Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama 790-8577, Japan Received April 12, 2001;
Revised Manuscript Received July 5, 2001
ABSTRACT: Helical-type of chiral cocrystal of tryptamine and hydrocinnamic acid was prepared by crystallization in the presence of different chiral crystals having similar crystal structures, despite spontaneous crystallization itself giving only achiral crystal. Chiral crystals formed from achiral molecules are utilized as reactants for absolute asymmetric synthesis by means of solid-state reactions.1-3 Such chiral crystals are also important for the development of new functional materials such as those used in nonlinear optics.4 Although chiral crystallization of achiral molecules occurs statistically with a low probability of around 5%,5-7 we have already succeeded in preparing various chiral two-component crystals through self-assembly of flexible molecules.3,8,9 In particular, a series of helicaltype crystals formed from tryptamine and achiral carboxylic acids were obtained with a probability of around 50%.9 Furthermore, their enantiomorphous control could be achieved by “pseudoseeding” based on utilizing these various helical-type crystals as seeds for each other. 10,11 This was significant because chiral crystallization of achiral molecules by itself always gives both enantiomorphous (left and right) crystals. Polymorphism, whereby a compound can crystallize in more than one different crystal structure, often occurs for organic molecules. However, it is sometimes difficult to obtain all such possible polymorphs due to the different crystallization variables required. Herein, we found that pseudoseeding could be successfully utilized to prepare chiral crystals, which is one of the polymorph forms, despite achiral crystals being usually formed by spontaneous crystallization. Crystals incorporating tryptamine (1) and hydrocinnamic acid (3-phenylpropionic acid) (2) were first prepared by spontaneous crystallization from a solution of both components in methanol (Chart 1). Achiral crystals 1‚2A in space group P21/n were the product obtained (Table 1). Our previous success in helicity control of a series of helical-type crystals by pseudoseeding10,11 reminded us that this method might be applicable in producing the chiral crystals 1‚2C, if these exist as one of the stable polymorphs. Chiral crystal 1‚311 formed from 1 and trans-cinnamic acid (3) was selected from a series of available helicaltype crystals as a pseudo-seed crystal, because the molecular structures of 2 and 3 are similar (Chart 1). The space group of 1‚3 belongs to P212121, and the absolute structures of P-1‚3 (clockwise helix) and M-1‚3 (counterclockwise helix) are also known.11 * To whom correspondence should be addressed. Fax: +81-89-9278523. E-mail:
[email protected].
Chart 1
Table 1. Crystal Data for Achiral 1‚2A and Chiral 1‚2C of the Tryptamine/Hydrocinnamic Acid Cocrystal cryst syst cryst size/mm temp/K a/Å b/Å c/Å space group cell vol/Å3 calcd density/g cm-3 Z data/params R Rw
1‚2A
1‚2C
monoclinic 0.3 × 0.4 × 0.2 293 15.658(5) 6.599(1) 16.411(2) P21/n 1679.1(7) 1.228 4 2547/221 0.045 0.062
orthorhombic 0.3 × 0.1 × 0.03 293 9.616(2) 26.251(8) 6.816(1) P212121 1720.6(7) 1.198 4 1516/209 0.130 0.103
A piece of a small single crystal of P-1‚3 was added to a slightly supersaturated solution of 1 and 2 in methanol and acetonitrile (1:1). The covered vessel was allowed to stand at room temperature, and fine needle crystals formed in a radial manner on the surface of the pseudo-seed crystal. These crystals were collected to afford around 10% yield, of which the amount of seed crystal was less than 0.1%. Next, measurement of solidstate CD spectra as Nujol mulls gave curve a in Figure 1, showing the formation of one-handed crystals of 1‚2C which are most probably the P-form on the analogy of successful enantiocontrol by pseudoseeding.10,11 Conversely, seeding using M-1‚3 in the same solution gave opposite handed crystals, most probably M-1‚2C, cor-
10.1021/cg0155189 CCC: $20.00 © 2001 American Chemical Society Published on Web 08/14/2001
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Crystal Growth & Design, Vol. 1, No. 5, 2001
Figure 1. Solid-state CD spectra of (a) P-1‚2C and (b) M-1‚2C.
responding to the CD curve b with a mirror image relationship to the curve a. The X-ray crystallographic analysis of 1‚2C confirmed its chiral nature, the space group being the same P212121 (Table 1) as that of seed crystal 1‚3, but with different unit cell dimensions from those of 1‚3 (a ) 9.681(3) Å, b ) 29.00(1) Å, c ) 5.931(4) Å). Thus, the effectiveness of pseudoseeding was confirmed for the chiralilty induction as well as the enantiocontrol. In addition, the chiral crystal 1‚411
Koshima and Miyauchi
formed from 1 and 4-chlorocinnamic acid (4) (Chart 1) also acts as a seed crystal for the formation of 1‚2C. The melting point of 1‚2A (146-148 °C) is slightly lower than 1‚2C (150-152 °C), but its density (1.228 g cm-3) is slightly larger than that of 1‚2C (1.198 g cm-3). The IR (KBr) absorptions are similar: 3226, 2446-3058 (broad), and 1537 cm-1 for 1‚2A and 3219, 2456-3059 (broad), and 1536 cm-1 for 1‚2C. These small differences in physical properties suggest the similarity of the molecular arrangements in the lattices of both crystals. In fact, NH3+‚‚‚CO2- quaternary ammonium salt bridge and In-NH‚‚‚O-C hydrogen bonding are commonly formed between the molecules of 1 and 2, both of which distances obtained from the X-ray crystallographic analyses are very similar. The NH3+‚‚‚CO2- distances are 1.86, 1.86, and 2.01 Å in 1‚2A and 1.88, 1.89, 1.98 Å in 1‚2C, and the In-NH‚‚‚O-C distances are 1.92 Å in 1‚2A and 1.95 Å in 1‚2C. In the lattice of achiral 1‚2A, a symmetrical molecular unit is formed between the two molecules of each component through the two kinds of intermolecular bonding (Figure 2a). The two pairs of symmetrical units are centrosymmetrically arranged in the unit cell (Z ) 4). On the other hand, a 2-fold helix is formed in chiral 1‚2C between the two components through the two types of intermolecular bonding (Figure 2b), and it is the existence of two pairs of unidirectional helices in the unit cell that induces the crystal chirality of 1‚2C.
Figure 2. Molecular arrangements of (a) symmetrical unit in the achiral crystal 1‚2A and (b) clockwise 2-fold helix in the chiral crystal P-1‚2C.
Polymorphs of a Cocrystal Prepared by Pseudoseeding
The InC-C-C-N torsion angles (62.2° and 63.1°) of the tryptamine aminoethyl group as well as the dihedral angles (86.7° and 96.8°) of the indole plane of 1 and phenyl plane of 2 are similar between the symmetrical unit (1‚2A) and the helix (1‚2C). The PhC-C-C-CO torsion angles of propionic acid group of 1 are, however, almost opposite at 66.2° and -68.7°, respectively. Thus, whether the molecules of 1 and 2 are arranged into the symmetrical unit or the helical structure depends on the conformation of the propionic acid group of 1. The following explanation may explain these successful chirality inductions. Strong intermolecular bondings of the NH3+‚‚‚CO2- salt bridge and the In-NH‚‚‚O-C hydrogen bond are common among all of the achiral and chiral crystals. The similar melting points as well as the similar crystal densities between 1‚2A and 1‚2C suggest their small energy differences in crystallization. Therefore, at the initial crystallization process from solution, the amino and imino groups of the tryptamine molecule and the carboxyl group of the acid molecule in solution are abstracted with highest priority to the helical binding sites on the surface of the seed crystals followed by continuing assembly in the same manner as the seed crystals, to form the corresponding chiral crystals. In other words, the seed helical binding sites act as templating growth points for crystal growth. Acknowledgment. We thank Dr. Motoo Shiro in Rigaku Corp. for the help of X-ray data analysis. This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology in Japan. Supporting Information Available: X-ray crystallographic information files (CIF) are available for 1‚2A and
Crystal Growth & Design, Vol. 1, No. 5, 2001 357 1‚2C. This material is available free of charge via the Internet at http://pubs.acs. org.
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