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Volume 68 
Part 9 
Pages o332-o334  
September 2012  

Received 19 June 2012
Accepted 20 July 2012
Online 1 August 2012

An optically resolved crystal of thiomalate: (S)-1-phenylethanaminium (R)-thiomalate

aDepartment of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan
Correspondence e-mail: konno@chem.sci.osaka-u.ac.jp

The asymmetric unit of the optically resolved title salt, C8H12N+·C4H5O4S-, contains a 1-phenylethanaminium monocation and a thiomalate (3-carboxy-2-sulfanylpropanoate) monoanion. The absolute configurations of the cation and the anion are determined to be S and R, respectively. In the crystal, cation-anion N-H...O hydrogen bonds, together with anion-anion O-H...O and S-H...O hydrogen bonds, construct a two-dimensional supramolecular sheet parallel to the ab plane. The two-dimensional sheet is linked with the upper and lower sheets through C-H...[pi] interactions to stack along the c axis.

Comment

Thiomalic acid (2-mercaptosuccinic acid, H3msa) is one of the simplest chiral thiol-containing dicarboxylic acids and has been widely employed as a raw material for sulfur-containing organic materials. Because commercially available H3msa is a racemic mixture of the S and R enantiomers, the preparation of enantiopure H3msa has been intensively investigated, prompted by the finding of efficient antirheumatic activity in a gold(I) adduct of the thiomalate ion, viz. {Na2[Au(msa)]·1.75H2O}n, by Nomiya et al. (1995[Nomiya, K., Yokoyama, H., Nagano, H., Oda, M. & Sakuma, S. (1995). Bull. Chem. Soc. Jpn, 68, 2875-2883.]). For example, LeBlanc et al. (1997[LeBlanc, D. J., Smith, R. W., Wang, Z., Howard-Lock, H. E. & Lock, C. J. L. (1997). J. Chem. Soc. Dalton Trans. pp. 3263-3267.]) reported the asymmetric synthesis of pure (R)-thiomalic acid from L-aspartic acid in three steps, while Shiraiwa et al. (1998[Shiraiwa, T., Ohkubo, M., Kubo, M., Miyazaki, H., Takehata, M., Izawa, H., Nakagawa, K. & Kurokawa, H. (1998). Chem. Pharm. Bull. 46, 1364-1369.]) reported the optical resolution of the racemic H3msa with the use of (S)-pea (pea = 1-phenylethanamine), which led to the preferential crystallization of the title compound, [(S)-Hpea]+·[(R)-H2msa]-, (I)[link]. The latter method is undoubtedly superior to the former, but the resulting salt, (I)[link], has not been crystallographically characterized.

As part of our studies on the rational construction of coordination systems based on chiral thiol-containing multidentate ligands (Konno, 2004[Konno, T. (2004). Bull. Chem. Soc. Jpn, 77, 627-649.]; Igashira-Kamiyama & Konno, 2011[Igashira-Kamiyama, A. & Konno, T. (2011). Dalton Trans. 40, 7249-7263.]), we started to investigate the coordination system derived from H3msa. In the course of this investigation, we obtained an optically active single crystal of (I)[link] from the reaction of racemic H3msa and (S)-pea, and its structure was determined by X-ray crystallography. The optical activity of the compound was confirmed by circular dichroism spectroscopy.

[Scheme 1]

The asymmetric unit of (I)[link] contains an [(S)-Hpea]+ cation and an [(R)-H2msa]- anion. The absolute configurations of cation and anion, which were confirmed by the Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]) parameter, are consistent with the previous prediction made by optical rotation measurements (Shiraiwa et al., 1998[Shiraiwa, T., Ohkubo, M., Kubo, M., Miyazaki, H., Takehata, M., Izawa, H., Nakagawa, K. & Kurokawa, H. (1998). Chem. Pharm. Bull. 46, 1364-1369.]). In (I)[link], the amine group of pea is protonated to form a [Hpea]+ cation, while one of the two carboxy groups of thiomalic acid (C3, O1 and O2) is protonated and the other (C4, O3 and O4) is deprotonated to form a [H2msa]- anion (Fig. 1[link]). Reflecting the protonation of the O1 atom, the C3-O1 bond length [1.297 (3) Å] is obviously longer than that of C3-O2 [1.213 (3) Å]. On the other hand, the difference between the C4-O3 [1.276 (2) Å] and C4-O4 [1.237 (3) Å] bond lengths is smaller, which is consistent with the deprotonated form of the COO- group. The other bond lengths and angles of the cation and the anion are in the ranges normally observed for related compounds.

In the crystal, the protonated carboxy group of each [(R)-H2msa]- anion acts as a hydrogen-bond donor, forming an intermolecular O-H...O hydrogen bond with a deprotonated carboxylate group of a neighbouring anion [O1...O3ii = 2.501 (2) Å; symmetry code: (ii) -x, y - [{1\over 2}], -z + 1]. In addition, its protonated carboxy group acts as a hydrogen-bond acceptor, forming an intermolecular S-H...O hydrogen bond with a thiol group of another neighbouring anion [S1...O2i = 3.2741 (19) Å; symmetry code: (i) -x + 1, y + [{1\over 2}], -z + 1]. Based on these two kinds of hydrogen bonds, [(R)-H2msa]- anions construct a two-dimensional grid network having rectangular cavities surrounded by four anions parallel to the ab plane (Fig. 2[link]). It is noted that each rectangular cavity accommodates an ammonium group of an [(S)-Hpea]+ cation through three N-H...O hydrogen bonds [N1...O4 = 2.751 (3) Å, N1...O3iii = 2.797 (2) Å and N1...O2iv = 2.845 (3) Å; symmetry codes: (iii) -x, y + [{1\over 2}], -z + 1; (iv) x, y + 1, z]. Besides these hydrogen-bonding interactions, two kinds of C-H...[pi] interactions exist in the crystal; one is a contact between a methine group of an [(R)-H2msa]- anion and a phenyl group of an [(S)-Hpea]+ cation [H1E...Cgii = 2.62 Å; Cg is the centroid of the C6-C12 ring; symmetry code: (ii) -x, y - [{1\over 2}], -z + 1], and the other is between a methine group of an [(S)-Hpea]+ cation and a phenyl group of a neighbouring cation [H6...Cgv = 2.85 Å; symmetry code: (v) -x, y + [{1\over 2}], -z] (Fig. 3[link]). The latter interaction connects the two-dimensional grids along the c axis, giving a three-dimensional structure in (I)[link].

From these structural features, it is likely that [(S)-Hpea]+ selects the R isomer of [H2msa]- such that each [(S)-Hpea]+ ammonium group forms multiple hydrogen bonds with three [H2msa]- carboxy groups and that each [(S)-Hpea]+ phenyl group forms a C-H...[pi] interaction with a [H2msa]- methine group, leading to the excellent optical resolution of the racemic H3msa with the use of (S)-pea.

[Figure 1]
Figure 1
A view of the asymmetric unit of (I)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2]
Figure 2
The two-dimensional grid network of [(R)-H2msa]- anions which incorporates ammonium groups of [(S)-Hpea]+ cations in (I)[link], viewed parallel to the crystallographic c axis. [(S)-Hpea]+ cations, except for their NH3+ groups, have been omitted for clarity. The grey dashed lines (red in the electronic version of the paper) show the hydrogen bonds between anions and the black broken lines show the hydrogen bonds between anions and cations. [Symmetry codes: (i) -x + 1, y + [{1\over 2}], -z + 1; (ii) -x, y - [{1\over 2}], -z + 1; (iii) -x, y + [{1\over 2}], -z + 1; (iv) x, y + 1, z.]
[Figure 3]
Figure 3
A view of the C-H...[pi] interaction network in (I)[link]. Dashed lines indicate the C-H...[pi] interactions.

Experimental

Compound (I)[link] was prepared according to the method of Shiraiwa et al. (1998[Shiraiwa, T., Ohkubo, M., Kubo, M., Miyazaki, H., Takehata, M., Izawa, H., Nakagawa, K. & Kurokawa, H. (1998). Chem. Pharm. Bull. 46, 1364-1369.]). (RS)-H3msa (5.0 g, 33 mmol) and (S)-pea (4.0 g, 33 mmol) were dissolved in propan-1-ol (27 ml). After allowing the mixture to stand in a freezer for one week, the crude product of (I)[link] (4.6 g) was collected by filtration. This product was dissolved in propan-1-ol at 353 K to give a colourless solution. The solution was cooled slowly to room temperature and colourless plate-shaped crystals of (I)[link] appeared after several hours.

Crystal data
  • C8H12N+·C4H5O4S-

  • Mr = 271.33

  • Monoclinic, P 21

  • a = 9.0547 (7) Å

  • b = 8.2304 (5) Å

  • c = 9.3016 (7) Å

  • [beta] = 92.760 (2)°

  • V = 692.39 (9) Å3

  • Z = 2

  • Mo K[alpha] radiation

  • [mu] = 0.24 mm-1

  • T = 200 K

  • 0.30 × 0.15 × 0.05 mm

Data collection
  • Rigaku R-AXIS RAPID diffractometer

  • Absorption correction: multi-scan (ABSCOR; Rigaku, 1995[Rigaku (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan.]) Tmin = 0.788, Tmax = 0.988

  • 6800 measured reflections

  • 3100 independent reflections

  • 2723 reflections with I > 2[sigma](I)

  • Rint = 0.034

Refinement
  • R[F2 > 2[sigma](F2)] = 0.041

  • wR(F2) = 0.107

  • S = 1.12

  • 3100 reflections

  • 179 parameters

  • 4 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • [Delta][rho]max = 0.40 e Å-3

  • [Delta][rho]min = -0.26 e Å-3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 1408 Friedel pairs

  • Flack parameter: 0.07 (8)

Table 1
Selected bond lengths (Å)

S1-C1 1.817 (2)
O1-C3 1.297 (3)
O2-C3 1.213 (3)
O3-C4 1.276 (2)
O4-C4 1.237 (3)

Table 2
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C6-C12 ring.

D-H...A D-H H...A D...A D-H...A
S1-H1...O2i 1.24 (3) 2.16 (3) 3.2741 (19) 148.0 (19)
O1-H1A...O3ii 0.96 (3) 1.54 (3) 2.501 (2) 177 (3)
N1-H1B...O4 0.94 (2) 1.84 (2) 2.751 (3) 162 (3)
N1-H1C...O3iii 0.92 (2) 1.94 (2) 2.797 (2) 154 (3)
N1-H1D...O2iv 0.89 (2) 2.10 (2) 2.845 (3) 141 (3)
C1-H1E...Cgii 1.00 2.62 3.56 156
C6-H6...Cgv 1.00 2.85 3.83 166
Symmetry codes: (i) [-x+1, y+{\script{1\over 2}}, -z+1]; (ii) [-x, y-{\script{1\over 2}}, -z+1]; (iii) [-x, y+{\script{1\over 2}}, -z+1]; (iv) x, y+1, z; (v) [-x, y+{\script{1\over 2}}, -z].

H atoms bound to C atoms were placed at calculated positions [C-H = 0.98 (CH3), 0.99 (CH2) and 1.00 Å (CH)] and refined as riding, with Uiso(H) = 1.2Ueq(C) for CH2 and CH groups, and 1.5Ueq(C) for methyl groups (rotating group model). H atoms bound to O and S atoms were located in a difference Fourier map and were refined with constrained displacement parameters [Uiso(H) = 1.2Ueq(O,S)]. H atoms bound to N atoms were located in a difference Fourier map and refined with distance restraints and constrained displacement parameters [N-H = 0.89 (2) Å and Uiso(H) = 1.5Ueq(N)].

Data collection: RAPID-AUTO (Rigaku, 2000[Rigaku (2000). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan.]); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SIR92 (Altomare et al., 1994[Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: Yadokari-XG 2009 (Kabuto et al., 2009[Kabuto, C., Akine, S., Nemoto, T. & Kwon, E. (2009). Nihon Kessho Gakkaishi, 51, 218-224.]); software used to prepare material for publication: Yadokari-XG 2009.


Supplementary data for this paper are available from the IUCr electronic archives (Reference: UK3047 ). Services for accessing these data are described at the back of the journal.


Acknowledgements

This work was supported by a Grant-in-Aid for Science Research (grant No. 23350026) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Izumi Science and Technology Foundation.

References

Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.  [CrossRef] [details]
Flack, H. D. (1983). Acta Cryst. A39, 876-881.  [CrossRef] [details]
Igashira-Kamiyama, A. & Konno, T. (2011). Dalton Trans. 40, 7249-7263.  [ChemPort] [PubMed]
Kabuto, C., Akine, S., Nemoto, T. & Kwon, E. (2009). Nihon Kessho Gakkaishi, 51, 218-224.  [CrossRef]
Konno, T. (2004). Bull. Chem. Soc. Jpn, 77, 627-649.  [ISI] [CrossRef] [ChemPort]
LeBlanc, D. J., Smith, R. W., Wang, Z., Howard-Lock, H. E. & Lock, C. J. L. (1997). J. Chem. Soc. Dalton Trans. pp. 3263-3267.  [CrossRef]
Nomiya, K., Yokoyama, H., Nagano, H., Oda, M. & Sakuma, S. (1995). Bull. Chem. Soc. Jpn, 68, 2875-2883.  [CrossRef] [ChemPort] [ISI]
Rigaku (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan.
Rigaku (2000). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Shiraiwa, T., Ohkubo, M., Kubo, M., Miyazaki, H., Takehata, M., Izawa, H., Nakagawa, K. & Kurokawa, H. (1998). Chem. Pharm. Bull. 46, 1364-1369.  [CrossRef] [ChemPort]


Acta Cryst (2012). C68, o332-o334   [ doi:10.1107/S0108270112032933 ]