1-[3,5-Bis(trifluoro­meth­yl)phen­yl]-3-[(5-ethenyl-1-aza­bicyclo­[2.2.2]octan-2-yl)(6-methoxy­quinolin-4-yl)meth­yl]thio­urea–l-proline–methanol (1/1/1)

Savitha Muramulla; Hadi D Arman; Cong-Gui Zhao; Edward R T Tiekink

doi:10.1107/S1600536809047072

. 2009 Nov 14;65(Pt 12):o3070. doi: 10.1107/S1600536809047072

1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl)(6-methoxyquinolin-4-yl)methyl]thiourea–l-proline–methanol (1/1/1)¹

Savitha Muramulla ^a, Hadi D Arman ^a, Cong-Gui Zhao ^a,^‡, Edward R T Tiekink ^b,^*

PMCID: PMC2972067 PMID: 21578800

Abstract

In the methanol solvate of the title 1:1 cocrystal, C₂₉H₂₈F₆N₄OS·C₅H₉NO₂·CH₄O, the l-proline molecule exists as a zwitterion. In the crystal, the disubstituted thiourea, l-proline and methanol molecules are linked by N—H⋯O and N—H⋯N hydrogen bonds, forming a two-dimensional array in the ab plane.

Related literature

For background to pre-catalyst molecules for the Michael addition of acetone to trans-β-nitrostyrene, see: Mandal & Zhao (2008 ▶). For a related structure, see: Muramulla et al. (2009 ▶). For discussion on the definition of a co-crystal, see: Zukerman-Schpector & Tiekink (2008 ▶). For the synthesis, see: Vakulya et al. (2005 ▶). graphic file with name e-65-o3070-scheme1.jpg

Experimental

Crystal data

C₂₉H₂₈F₆N₄OS·C₅H₉NO₂·CH₄O
M _r = 741.79
Orthorhombic,
a = 11.597 (3) Å
b = 13.044 (4) Å
c = 23.907 (7) Å
V = 3616.4 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.17 mm⁻¹
T = 98 K
0.28 × 0.25 × 0.05 mm

Data collection

Rigaku AFC12K/SATURN724 diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T _min = 0.722, T _max = 1.000
26093 measured reflections
8250 independent reflections
7519 reflections with I > 2σ(I)
R _int = 0.059

Refinement

R[F ² > 2σ(F ²)] = 0.060
wR(F ²) = 0.149
S = 1.06
8250 reflections
471 parameters
3 restraints
H-atom parameters constrained
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.27 e Å⁻³
Absolute structure: Flack (1983 ▶), 3638 Friedel pairs
Flack parameter: −0.03 (10)

Data collection: CrystalClear (Rigaku/MSC 2005 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809047072/hb5216sup1.cif

e-65-o3070-sup1.cif^{(31.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809047072/hb5216Isup2.hkl

e-65-o3070-Isup2.hkl^{(395.5KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1n⋯O2ⁱ	0.88	1.87	2.749 (3)	177
N2—H2n⋯O3ⁱ	0.88	1.95	2.806 (3)	165
N5—H5a⋯N4	0.92	2.16	2.912 (3)	138
N5—H5a⋯O3ⁱ	0.92	2.40	3.111 (3)	134
N5—H5b⋯O4ⁱⁱ	0.92	2.03	2.858 (3)	149
O4—H4o⋯N3ⁱⁱⁱ	0.84	1.98	2.805 (4)	168

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

CGZ thanks the National Science Foundation (grant No. CHE-0909954) for financial support of this project.

supplementary crystallographic information

Comment

The title co-crystal (Zukerman-Schpector & Tiekink, 2008), (I), has been evaluated as a pre-catalyst for the Michael addition of acetone to trans-β-nitrostyrene (Mandal & Zhao, 2008; Muramulla et al., 2009). The combination of quinidine thiourea and L-proline is activating both the nucleophile and electrophile of the Michael reactions. The asymmetric Michael addition of acidic carbon pronucleophiles to nitroolefins is an important carbon-carbon bond forming reaction that provides access to synthetically useful enantioenriched nitroalkanes.

The absolute structure of the co-crystal, isolated as a methanol solvate, (I), has been determined, Figs 1 and 2, and reveals the chirality at the N4, C10, C21, C23, C24 and C30 atoms of the disubstituted thiourea molecule to be S, R, R, R, S and S, respectively. The L-proline molecule exists as a zwitterion, a conclusion confirmed by the equality of the C35–O2 (1.257 (3) Å) and C35–O3 distances (1.250 (4) Å), and by the pattern of hydrogen bonding interactions involving both ammonium-H atoms. The proline ring conformation is an envelope on atom C(32).

In the crystal structure, molecules are connected into a supramolecular chain along the a axis which, in turn, are connected into layers in the ab plane, Table 1. Each N–H atom of the disubstituted urea molecule is hydrogen bonded to a carboxylate-O atom. One of the ammonium-H atoms of the proline molecule links a neighbouring molecule by forming an N5–H5a···N4 hydrogen bond with the nitrogen atom of the dabco residue; the H5a atom also forms a weak N–H···O contact with a carboxylate-O3 atom to provide extra stability to the chain. The second ammonium-H forms a N–H···O hydrogen bond with the solvent methanol molecule. As shown in Fig. 3, the hydrogen bonding scheme described thus far leads to the formation of a supramolecular chain. The pyridine-N3 atoms are directed to the periphery of this chain and these hydrogen bond with the methanol molecule to form links between chains to generate a 2-D array, Fig. 4.

Experimental

Compound (I) was prepared from the reaction of quinidine thiourea (30 mg, 0.05 mmol), prepared using a literature procedure (Vakulya et al., 2005), and L-proline (Sigma Aldrich; 0.05 mmol) in a 1:1 ratio in methanol (2 ml). The vial was left uncorked and kept in a beaker half filled with pentane sealed with parafilm. After 1 day, crystals were isolated.