organic compounds
tert-Butyl 2-sulfanylidene-2,3-dihydro-1H-imidazole-1-carboxylate
aDepartment of Applied Cosmetology and Graduate Institute of Cosmetic Science, Hungkuang University, Taichung 433, Taiwan, and bDepartment of Chemistry, National Chung Hsing University, Taichung 402, Taiwan
*Correspondence e-mail: mjchen@sunrise.hk.edu.tw
In the title molecule, C8H12N2O2S, the imidazole ring forms a dihedral angle of 5.9 (2)° with the mean plane of the carboxylate group. In the crystal, molecules are linked by pairs of N—H⋯S hydrogen bonds, forming inversion dimers.
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 related structures containing intermolecular N—H⋯S hydrogen bonds, see: Krepps et al. (2001).
Experimental
Crystal data
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Refinement
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Data collection: CrysAlis PRO (Agilent, 2011); cell 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.
Supporting information
https://doi.org/10.1107/S1600536812027924/lh5490sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812027924/lh5490Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536812027924/lh5490Isup3.cml
To a mixture of 2-mercaptoimidazole (351 mg, 3.5 mmole) and potassium carbonate (968 mg, 7 mmole) in 7 ml of N,N-dimethylformamide was added di-tert-butyl dicarbonate (1.1 ml, 5.2 mmol). The reaction mixture was stirred at 298 K for 24 h under N2 atmosphere. The resulting mixture was partitioned between ethyl acetate (40 ml) and H2O (20 ml). The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was separated by
over silica gel and eluted with hexane/ethyl acetate (3/7) to afford 297 mg of the title compound (I) in 42% yield. Single crystals suitable for X-ray measurements were obtained by recrystallization from a dichloromethane/hexane solution of the title compound at room temperature. Anal. Calcd for C8H12N2O2S: C, 47.98; H, 6.04; N, 13.99; Found: C, 47.86; H, 6.14; N, 13.92.All H atoms were placed in geometrically idealized positions and treated as riding on their parent atoms, with C—H = 0.93 - 0.96 Å, N—H = 0.86 Å and Uiso(H) > 1.2Ueq(C,N) or 1.5 Ueq(Cmethyl).
1-methyl-2-mercaptoimidazole causes hypopigmentation by inhibiting tyrosinase in the clinical oral antithyroid medication (Kasraee (2002); Kasraee et al., 2005). Ergothioneine has a significant effect on inhibiting tyrosinase
resulting from the presence of the sulfur substituent in the imidazole ring (Liao et al., 2012). It shows that molecules with a 2-mercaptoimidazole group have potential as skin whitening agents. In this regard, we report here the synthesis and of the title compound. The molecular structure of the title compound is shown in Fig. 1. The essentially planar imidazoline ring (C1/C2/C3/N1/N2) forms a dihedral angle of 5.9 (2)° with the mean plane of the carboxylate group (N2/C4/O1/O2). In the crystal, pairs of molecules are linked by N—H···S hydrogen bonds to form inversion dimers. Intermolecular N—H···S hydrogen bonds are highlighted in the literature by Krepps et al. (2001).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 related structures containing intermolecular N—H···S hydrogen bonds, see: Krepps et al. (2001).
Data collection: CrysAlis PRO (Agilent, 2011); cell
CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); 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 (Sheldrick, 2008).Fig. 1. The molecular structure of (I), with ellipsoids for non-H atoms shown at the 50% probability level. |
C8H12N2O2S | - |
Mr = 200.26 | Dx = 1.248 Mg m−3 |
Monoclinic, P21/c | Melting point: 439 K |
Hall symbol: -P 2ybc | Mo Kα radiation, λ = 0.71073 Å |
a = 6.8316 (3) Å | Cell parameters from 1507 reflections |
b = 8.8893 (5) Å | θ = 3.0–29.2° |
c = 17.5458 (15) Å | µ = 0.28 mm−1 |
β = 90.789 (6)° | T = 293 K |
V = 1065.42 (12) Å3 | Parallelpiped, colourless |
Z = 4 | 0.60 × 0.50 × 0.35 mm |
F(000) = 424 |
Agilent Xcalibur Sapphire3 Gemini diffractometer | 2472 independent reflections |
Radiation source: fine-focus sealed tube | 1808 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.047 |
Detector resolution: 16.0690 pixels mm-1 | θmax = 29.2°, θmin = 3.0° |
ω scans | h = −9→9 |
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011) | k = −11→11 |
Tmin = 0.859, Tmax = 1.000 | l = −23→21 |
4722 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.070 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.213 | H-atom parameters constrained |
S = 1.09 | w = 1/[σ2(Fo2) + (0.120P)2] where P = (Fo2 + 2Fc2)/3 |
2472 reflections | (Δ/σ)max < 0.001 |
118 parameters | Δρmax = 0.37 e Å−3 |
0 restraints | Δρmin = −0.67 e Å−3 |
C8H12N2O2S | V = 1065.42 (12) Å3 |
Mr = 200.26 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 6.8316 (3) Å | µ = 0.28 mm−1 |
b = 8.8893 (5) Å | T = 293 K |
c = 17.5458 (15) Å | 0.60 × 0.50 × 0.35 mm |
β = 90.789 (6)° |
Agilent Xcalibur Sapphire3 Gemini diffractometer | 2472 independent reflections |
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011) | 1808 reflections with I > 2σ(I) |
Tmin = 0.859, Tmax = 1.000 | Rint = 0.047 |
4722 measured reflections |
R[F2 > 2σ(F2)] = 0.070 | 0 restraints |
wR(F2) = 0.213 | H-atom parameters constrained |
S = 1.09 | Δρmax = 0.37 e Å−3 |
2472 reflections | Δρmin = −0.67 e Å−3 |
118 parameters |
Experimental. Absorption correction: CrysAlisPro, Agilent Technologies, Version 1.171.35.19 (release 27-10-2011 CrysAlis171 .NET) (compiled Oct 27 2011,15:02:11) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
S | 0.27124 (9) | 0.62848 (7) | 0.03744 (6) | 0.0726 (4) | |
O1 | 0.3738 (3) | 0.9165 (2) | 0.12448 (15) | 0.0823 (8) | |
O2 | 0.1365 (3) | 1.08602 (18) | 0.14513 (10) | 0.0541 (5) | |
N1 | −0.1123 (3) | 0.6966 (2) | 0.03370 (11) | 0.0468 (5) | |
H1A | −0.1457 | 0.6126 | 0.0129 | 0.056* | |
N2 | 0.0567 (3) | 0.87696 (19) | 0.08377 (11) | 0.0389 (5) | |
C1 | 0.0732 (3) | 0.7337 (2) | 0.05224 (13) | 0.0415 (5) | |
C2 | −0.2421 (3) | 0.8086 (3) | 0.05181 (14) | 0.0508 (6) | |
H2A | −0.3770 | 0.8061 | 0.0440 | 0.061* | |
C3 | −0.1412 (3) | 0.9201 (3) | 0.08217 (13) | 0.0472 (6) | |
H3A | −0.1916 | 1.0109 | 0.0994 | 0.057* | |
C4 | 0.2096 (3) | 0.9595 (3) | 0.11969 (14) | 0.0469 (6) | |
C5 | 0.2572 (4) | 1.1899 (3) | 0.19323 (15) | 0.0587 (7) | |
C6 | 0.1128 (6) | 1.3169 (4) | 0.2072 (2) | 0.0962 (12) | |
H6A | 0.0046 | 1.2795 | 0.2360 | 0.144* | |
H6B | 0.0656 | 1.3553 | 0.1592 | 0.144* | |
H6C | 0.1769 | 1.3960 | 0.2352 | 0.144* | |
C7 | 0.4278 (5) | 1.2477 (4) | 0.1471 (2) | 0.0896 (11) | |
H7A | 0.5177 | 1.1669 | 0.1379 | 0.134* | |
H7B | 0.4935 | 1.3264 | 0.1748 | 0.134* | |
H7C | 0.3800 | 1.2865 | 0.0992 | 0.134* | |
C8 | 0.3180 (8) | 1.1119 (4) | 0.2653 (2) | 0.1084 (15) | |
H8A | 0.4083 | 1.0327 | 0.2538 | 0.163* | |
H8B | 0.2047 | 1.0702 | 0.2893 | 0.163* | |
H8C | 0.3798 | 1.1829 | 0.2992 | 0.163* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S | 0.0365 (4) | 0.0442 (5) | 0.1370 (8) | −0.0011 (3) | 0.0015 (4) | −0.0349 (4) |
O1 | 0.0419 (11) | 0.0628 (12) | 0.142 (2) | 0.0071 (9) | −0.0166 (12) | −0.0510 (13) |
O2 | 0.0475 (10) | 0.0450 (9) | 0.0696 (11) | 0.0052 (8) | −0.0040 (8) | −0.0234 (8) |
N1 | 0.0350 (10) | 0.0458 (11) | 0.0598 (11) | −0.0064 (9) | 0.0021 (8) | −0.0122 (9) |
N2 | 0.0304 (9) | 0.0365 (9) | 0.0501 (10) | 0.0008 (7) | 0.0051 (7) | −0.0070 (8) |
C1 | 0.0348 (12) | 0.0363 (11) | 0.0535 (12) | −0.0065 (9) | 0.0045 (9) | −0.0055 (10) |
C2 | 0.0310 (11) | 0.0640 (16) | 0.0574 (14) | 0.0018 (11) | 0.0019 (10) | −0.0141 (12) |
C3 | 0.0346 (12) | 0.0546 (14) | 0.0525 (13) | 0.0079 (10) | 0.0028 (9) | −0.0103 (11) |
C4 | 0.0383 (12) | 0.0404 (12) | 0.0622 (14) | 0.0022 (10) | 0.0011 (10) | −0.0125 (11) |
C5 | 0.0710 (18) | 0.0431 (13) | 0.0619 (15) | −0.0010 (13) | −0.0053 (13) | −0.0206 (12) |
C6 | 0.104 (3) | 0.0696 (19) | 0.115 (3) | 0.014 (2) | −0.003 (2) | −0.048 (2) |
C7 | 0.090 (2) | 0.0680 (19) | 0.111 (3) | −0.0256 (19) | 0.000 (2) | −0.029 (2) |
C8 | 0.167 (5) | 0.082 (3) | 0.075 (2) | 0.001 (2) | −0.038 (2) | −0.0115 (19) |
S—C1 | 1.668 (2) | C5—C8 | 1.496 (5) |
O1—C4 | 1.186 (3) | C5—C7 | 1.518 (4) |
O2—C4 | 1.312 (3) | C5—C6 | 1.521 (4) |
O2—C5 | 1.492 (3) | C6—H6A | 0.9600 |
N1—C1 | 1.345 (3) | C6—H6B | 0.9600 |
N1—C2 | 1.374 (3) | C6—H6C | 0.9600 |
N1—H1A | 0.8600 | C7—H7A | 0.9600 |
N2—C1 | 1.394 (3) | C7—H7B | 0.9600 |
N2—C3 | 1.405 (3) | C7—H7C | 0.9600 |
N2—C4 | 1.417 (3) | C8—H8A | 0.9600 |
C2—C3 | 1.316 (3) | C8—H8B | 0.9600 |
C2—H2A | 0.9300 | C8—H8C | 0.9600 |
C3—H3A | 0.9300 | ||
C4—O2—C5 | 120.9 (2) | O2—C5—C6 | 101.3 (2) |
C1—N1—C2 | 112.04 (19) | C8—C5—C6 | 112.4 (3) |
C1—N1—H1A | 124.0 | C7—C5—C6 | 109.8 (3) |
C2—N1—H1A | 124.0 | C5—C6—H6A | 109.5 |
C1—N2—C3 | 108.91 (18) | C5—C6—H6B | 109.5 |
C1—N2—C4 | 125.90 (19) | H6A—C6—H6B | 109.5 |
C3—N2—C4 | 124.82 (19) | C5—C6—H6C | 109.5 |
N1—C1—N2 | 103.84 (18) | H6A—C6—H6C | 109.5 |
N1—C1—S | 126.03 (17) | H6B—C6—H6C | 109.5 |
N2—C1—S | 130.11 (16) | C5—C7—H7A | 109.5 |
C3—C2—N1 | 107.6 (2) | C5—C7—H7B | 109.5 |
C3—C2—H2A | 126.2 | H7A—C7—H7B | 109.5 |
N1—C2—H2A | 126.2 | C5—C7—H7C | 109.5 |
C2—C3—N2 | 107.6 (2) | H7A—C7—H7C | 109.5 |
C2—C3—H3A | 126.2 | H7B—C7—H7C | 109.5 |
N2—C3—H3A | 126.2 | C5—C8—H8A | 109.5 |
O1—C4—O2 | 128.0 (2) | C5—C8—H8B | 109.5 |
O1—C4—N2 | 123.7 (2) | H8A—C8—H8B | 109.5 |
O2—C4—N2 | 108.25 (19) | C5—C8—H8C | 109.5 |
O2—C5—C8 | 109.7 (2) | H8A—C8—H8C | 109.5 |
O2—C5—C7 | 109.3 (2) | H8B—C8—H8C | 109.5 |
C8—C5—C7 | 113.7 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···Si | 0.86 | 2.47 | 3.324 (2) | 174 |
Symmetry code: (i) −x, −y+1, −z. |
Experimental details
Crystal data | |
Chemical formula | C8H12N2O2S |
Mr | 200.26 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 6.8316 (3), 8.8893 (5), 17.5458 (15) |
β (°) | 90.789 (6) |
V (Å3) | 1065.42 (12) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.28 |
Crystal size (mm) | 0.60 × 0.50 × 0.35 |
Data collection | |
Diffractometer | Agilent Xcalibur Sapphire3 Gemini |
Absorption correction | Multi-scan (CrysAlis PRO; Agilent, 2011) |
Tmin, Tmax | 0.859, 1.000 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4722, 2472, 1808 |
Rint | 0.047 |
(sin θ/λ)max (Å−1) | 0.687 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.070, 0.213, 1.09 |
No. of reflections | 2472 |
No. of parameters | 118 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.37, −0.67 |
Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···Si | 0.86 | 2.47 | 3.324 (2) | 173.9 |
Symmetry code: (i) −x, −y+1, −z. |
Acknowledgements
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.
References
Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, England. Google Scholar
Kasraee, B. (2002). J. Invest. Dermatol. 118, 205–207. Web of Science CrossRef PubMed CAS Google Scholar
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1-methyl-2-mercaptoimidazole causes hypopigmentation by inhibiting tyrosinase in the clinical oral antithyroid medication (Kasraee (2002); Kasraee et al., 2005). Ergothioneine has a significant effect on inhibiting tyrosinase enzyme activity, resulting from the presence of the sulfur substituent in the imidazole ring (Liao et al., 2012). It shows that molecules with a 2-mercaptoimidazole group have potential as skin whitening agents. In this regard, we report here the synthesis and crystal structure of the title compound. The molecular structure of the title compound is shown in Fig. 1. The essentially planar imidazoline ring (C1/C2/C3/N1/N2) forms a dihedral angle of 5.9 (2)° with the mean plane of the carboxylate group (N2/C4/O1/O2). In the crystal, pairs of molecules are linked by N—H···S hydrogen bonds to form inversion dimers. Intermolecular N—H···S hydrogen bonds are highlighted in the literature by Krepps et al. (2001).