Methyl 2-[(tert-but­oxy­carbon­yl)amino]-3-(3-methyl-2-sulfanyl­idene-2,3-dihydro-1H-imidazol-1-yl)propano­ate

Chin-Feng Chan; Yi-Cin Guo; Bor-Hunn Huang; Ming-Jen Chen

doi:10.1107/S1600536812043486

. 2012 Oct 24;68(Pt 11):o3206. doi: 10.1107/S1600536812043486

Methyl 2-[(tert-butoxycarbonyl)amino]-3-(3-methyl-2-sulfanylidene-2,3-dihydro-1H-imidazol-1-yl)propanoate

Chin-Feng Chan ^a, Yi-Cin Guo ^a, Bor-Hunn Huang ^b, Ming-Jen Chen ^a,^*

PMCID: PMC3515294 PMID: 23284514

Abstract

In the title compound, C₁₃H₂₁N₃O₄S, the mean plane of the –N(H)—C(=O)—O– group of the carbamate unit forms a dihedral angle of 64.7 (2)° with the mean plane of the –C—C(=O)—O– group of the ester unit. In the crystal, molecules are linked by N—H⋯O=C hydrogen bonds, forming chains along the c-axis direction.

Related literature

The title compound is a mercaptoimidazole derivative. For applications of mercaptoimidazole derivatives in the treatment of hyperpigmentation, see: Kasraee (2002 ▶); Kasraee et al. (2005 ▶) and for inhibiting tyrosinase, see: Liao et al. (2012 ▶). For typical bond lengths of intermolecular N—H⋯O=C hydrogen bonds, see: Taylor et al. (1984 ▶).

Experimental

Crystal data

C₁₃H₂₁N₃O₄S
M _r = 315.39
Monoclinic,
a = 8.7636 (1) Å
b = 19.1184 (2) Å
c = 9.6735 (2) Å
β = 98.485 (1)°
V = 1603.02 (4) Å³
Z = 4
Cu Kα radiation
μ = 1.97 mm⁻¹
T = 110 K
0.60 × 0.50 × 0.30 mm

Data collection

Agilent Xcalibur (Sapphire3, Gemini) diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ▶) T _min = 0.550, T _max = 1.000
12262 measured reflections
3093 independent reflections
2923 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.137
S = 1.05
3093 reflections
190 parameters
H-atom parameters constrained
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.53 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Click here for additional data file.^{(17.6KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812043486/lh5544sup1.cif

e-68-o3206-sup1.cif^{(17.6KB, cif)}

Click here for additional data file.^{(151.8KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812043486/lh5544Isup2.hkl

e-68-o3206-Isup2.hkl^{(151.8KB, hkl)}

Click here for additional data file.^{(6KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812043486/lh5544Isup3.cml

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
N3—H3A⋯O1ⁱ	0.88	2.25	2.9819 (14)	140

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Symmetry code: (i) Inline graphic .

Acknowledgments

We gratefully acknowledge financial support in part from the National Science Council, Taiwan (NSC 99–2119-M-241-001-MY2). Helpful comments from the reviewers are also greatly appreciated.

supplementary crystallographic information

Comment

Methimazole causes hypopigmentation in some patients during the clinical oral antithyroid medication (Kasraee, 2002; Kasraee et al., 2005). Ergothioneine has a potent inhibition effect on inhibiting tyrosinase enzyme activity, resulting from the presence of the sulfur substituted imidazole ring (Liao et al., 2012). It shows that molecules with a mercaptoimidazole group have potential as depigmenting agents. The title compound (I) is the key intermediate for the synthesis of the amino acid derivatives containing methimazole moiety. Methimazole exists between the 2-thiol and 2-thione forms and has been observed to react in both guizes, depending upon the reaction conditions. Compound (I) is the nitrogen-substituted product from the 2-thione form.

Herein we report the synthesis and crystal structure of the title compound. The molecular structure of (I) is shown in Fig. 1. The essentially planar carbamate group (N3/C7/O1/O2) forms a dihedral angle of 64.7 (2)° with the mean plane of the carboxylate group (C6/C12/O3/O4). In the crystal, molecules are linked by N—H···O═C hydrogen bonds involving the amino and carbamate group forming chains along the c-axis direction. Intermolecular N—H···O═C hydrogen bonds are are highlighted in the literature by Taylor et al. (1984).

Experimental

To a mixture of 1-methyl-2-mercaptoimidazole (390 mg, 3.4 mmole) and methyl 3-bromo-2-[(tert-butoxycarbonyl)amino]propanoate (970 mg, 3.4 mmol) in 17 ml of N,N-dimethylformamide was added potassium carbonate (940 mg, 6.8 mmole). The reaction mixture was stirred at 343 K for 1.5 h under N₂ atmosphere. The resulting mixture was partitioned between dichloromethane (70 ml) and H₂O (35 ml). The organic layer was dried over MgSO₄ and concentrated in vacuo. The residue was separated by chromatography over silica gel and eluted with hexane/ethyl acetate (3/7) to afford 776 mg of the title compound (I) in 72% yield. Single crystals suitable for X-ray measurements were obtained by recrystallization from a dichloromethane/hexane solution of the title compound at room temperature.