Crystal structures of four chiral imine-substituted thiophene derivatives

Thiophenes substituted in position 2 and 5 by chiral imine groups display non-crystallographic or crystallographic twofold symmetry.


Chemical context
Thiophenedicarbaldehydes have a variety of applications (Dean, 1982a,b), for instance in the synthesis of annulenones and polyenyl-substituted thiophenes (Sargent & Cresp, 1975), in the preparation of macrocyclic ligands for bimetallic complexes that are able to mimic enzymes (Nelson et al., 1983), in crown ether chemistry (Cram & Trueblood, 1981) and, more recently, in the preparation of azomethines for photovoltaic applications (Bolduc et al., 2013a,b;Petrus et al., 2014). In regard to this latter application, most of the conjugated materials used in organic electronics are synthesized using time-consuming Suzuki-, Wittig-, or Heck-type coupling reactions that require expensive catalysts, stringent reaction conditions, and tedious purification processes. In order to afford a more economic route towards organic photovoltaic materials, Schiff bases derived from 2,5-thiophenedicarbaldehyde as the conjugated linker unit have recently been used. The azomethine bond, which is isoelectronic with the vinyl bond and possesses similar optoelectronic and thermal properties, is easily accessible through the Schiff condensation under near ambient reaction conditions (Morgan et al., 1987;Pé rez Guarìn et al., 2007;Sicard et al., 2013). ISSN 2056-9890 We report here the synthesis and X-ray characterization of such thiophene derivatives, as a continuation of a partially published record (Bernè s et al., 2013;Mendoza et al., 2014). We are improving a general solvent-free approach for these syntheses, recognising that ecological aspects in organic chemistry have become a priority, in order to minimize the quantity of toxic waste and by-products, and to decrease the amount of solvent in the reaction media or during work-up (Tanaka & Toda, 2000;Noyori, 2005).
In the synthesis of the thiophenes reported here, the Schiff condensation generates a single by-product, water, and a onestep recrystallization affords the pure substituted thiophene in nearly quantitative yields. Our protocol may be readily extended to any low molecular weight 2,5-susbtituted thiophene, providing that a liquid amine is used for the condensation. In the present work, the starting material is 2,5thiophenedicarbaldehyde, a low melting-point compound (m.p. = 388-390 K), and four chiral amines were used. We took advantage of the anomalous dispersion of the sulfur sites to confirm that the configuration of the chiral amine is retained during the condensation.

Structural commentary
The first compound was synthesized using (S)-(+)-1-aminotetraline. The Schiff base (I), C 26 H 26 N 2 S, crystallizes in the space group P1, with the expected absolute configuration ( Fig. 1). The general shape of the molecule displays a pseudotwofold axis, passing through the S atom and the midpoint of the thiophene C-C -bond. As a consequence, the independent benzene rings are placed above and below the thiophene ring, and are inclined to one another at a dihedral angle of 73.76 (15) . The central core containing the thiophene ring and the imine bonds is virtually planar, and the imine bonds are substituted by the tetralin ring systems, which present the same conformation. The aliphatic rings C9-C13/C18 and C19-C23/C28 each have a half-chair conformation.
Compound (II), C 24 H 26 N 2 O 2 S, was obtained using (R)-(+)-(4-methoxy)phenylethylamine as the chiral component in the Schiff condensation. The twofold molecular axis, which was a latent symmetry in the case of (I), is a true crystallographic symmetry in (II), and this compound crystallizes in the space group C2 (Fig. 2). The asymmetric unit thus contains half a The molecular structure of (I), with displacement ellipsoids for non-H atoms at the 30% probability level.

Figure 2
The molecular structure of (II), with displacement ellipsoids for non-H atoms at the 30% probability level. Non-labeled atoms are generated by symmetry code (1 À x, y, 1 À z).

Figure 3
The molecular structures of isomorphous compounds (III) and (IV), with displacement ellipsoids for non-H atoms at the 30% probability level. Notice the different configuration for chiral center C5 in (III) and (IV). Non-labeled atoms are generated by symmetry codes (1 À x, Ày, z) and (1 À x, 2 À y, z) for (III) and (IV), respectively. molecule, and the molecular conformation for the complete molecule is similar to that of (I). The benzene rings have a free relative orientation, since these rings are not fused in a bicyclic system, as in (I); the dihedral angle between symmetry-related rings is 61.30 (7) .
Compounds (III) and (IV), synthesized with enantiomerically pure (4-halogen)phenylethylamines (halogen = F, Cl) are isomorphous and crystallize with orthorhombic unit cells. The latent twofold symmetry of (I) is again observed, since both molecules lie on the crystallographic twofold axes of the space group P2 1 2 1 2 (Fig. 3). The dihedral angle between the benzene rings is close to that observed for (II): 64.18 (8) for (III) and 62.03 (9) for (IV). The same Schiff base but with Br as the halogen substituent has been published previously (Mendoza et al., 2014), but is not isomorphous with (III) and (IV). Instead, this molecule was found to crystallize in the space group C2, with unit-cell parameters and a crystal structure very similar to those of (II). A systematic trend is thus emerging for these 2,5-substituted thiophenes, related to the potential twofold molecular symmetry: they have a strong tendency to crystallize in space groups that include at least one C 2 axis, such as C2 and P2 1 2 1 2 for the chiral crystals. This trend extends to achiral molecules, which also have twofold crystallographic symmetry in the space group C2/c (Kudyakova et al., 2011;Suganya et al., 2014;Boyle et al., 2015;Moussallem et al., 2015). The features shared by these related compounds could also be a signature of a propensity towards polymorphism between monoclinic and orthorhombic systems.
The difference between non-crystallographic symmetry in (I) and exact C 2 molecular symmetry in (II)-(IV) is also reflected in the degree of conjugation between thiophene rings and imine bonds. For (I), dihedral angles between the thiophene and C N-C * mean planes (C * is the chiral C atom bonded to the imine functionality) are 6.9 (7) and 1.9 (6) . Other crystals have a symmetry restriction, inducing a small deconjugation of the imine bonds. The corresponding dihedral angles with the thiophene rings are 8.5 (4), 10.1 (3), and 9.8 (3) , for (II), (III) and (IV), respectively.

Supramolecular features
Although all compounds have benzene rings, neithernor C-HÁ Á Á contacts stabilize the crystal structures. However, these compounds share a common supramolecular feature. Lone pairs of S atoms interact with thiophenic CH groups of a neighboring molecule in the crystal, forming chains along the short cell axes: [100] for (I), [010] for (II) and [001] for (III) and (IV). An example is presented in Fig. 4, for compound (II). These bifurcated SÁ Á ÁC-H contacts have a significant strength for (I), perhaps as a consequence of the relaxed molecular symmetry in space group P1. The contacts are weaker for (II), (III) and (IV), which have a geometry restrained by the crystallographic symmetry (Table 1).
The group of chiral molecules belonging to this family is much less populated, with two examples reported by our group in this journal. Both are molecules with the C 2 point group and crystallize in space groups C2 (Mendoza et al., 2014) and P22 1 2 1 (Bernè s et al., 2013).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. No unusual issues appeared, and refinements were carried out on non-restricted models. All H atoms were placed in calculated positions, and refined as riding on their carrier C atoms, with C-H bond lengths fixed to 0.93 (aromatic CH), 0.96 (methyl CH 3 ), 0.97 (methylene   CH 2 ), or 0.98 Å (methine CH). Isotropic displacement parameters were calculated as U iso (H) = 1.5U eq (C) for methyl H atoms and U iso (H) = 1.2U eq (C) for other H atoms. For all compounds, the absolute configuration was based on the refinement of the Flack parameter (Parsons et al., 2013), confirming that the configuration of the chiral amine used as the starting material was retained during the Schiff condensation.