organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

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

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

(Received 12 October 2012; accepted 19 October 2012; online 24 October 2012)

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, B. (2002). J. Invest. Dermatol. 118, 205-207.]); Kasraee et al. (2005[Kasraee, B., Handjani, F., Parhizgar, A., Omrani, G. R., Fallahi, M. R., Amini, M., Nikbakhsh, M., Tran, C., Hügin, A., Sorg, O. & Saurat, J.-H. (2005). Dermatology, 211, 360-362.]) and for inhibiting tyrosinase, see: Liao et al. (2012[Liao, W. C., Wu, W. H., Tsai, P.-C., Wang, H.-F., Liu, Y.-H. & Chan, C.-F. (2012). Appl. Biochem. Biotechnol. 166, 259-267.]). For typical bond lengths of inter­molecular N—H⋯O=C hydrogen bonds, see: Taylor et al. (1984[Taylor, R., Kennard, O. & Versichel, W. (1984). Acta Cryst. B40, 280-288.]).

[Scheme 1]

Experimental

Crystal data
  • C13H21N3O4S

  • Mr = 315.39

  • Monoclinic, P 21 /c

  • 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[Agilent (2010). CrysAlis PRO. Agilent Technologies, Yarnton, England.]) Tmin = 0.550, Tmax = 1.000

  • 12262 measured reflections

  • 3093 independent reflections

  • 2923 reflections with I > 2σ(I)

  • Rint = 0.019

Refinement
  • R[F2 > 2σ(F2)] = 0.036

  • wR(F2) = 0.137

  • S = 1.05

  • 3093 reflections

  • 190 parameters

  • H-atom parameters constrained

  • Δρmax = 0.39 e Å−3

  • Δρmin = −0.53 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N3—H3A⋯O1i 0.88 2.25 2.9819 (14) 140
Symmetry code: (i) [x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}].

Data collection: CrysAlis PRO (Agilent, 2010[Agilent (2010). CrysAlis PRO. Agilent Technologies, Yarnton, England.]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97.

Supporting information


Comment top

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···OC hydrogen bonds involving the amino and carbamate group forming chains along the c-axis direction. Intermolecular N—H···OC hydrogen bonds are are highlighted in the literature by Taylor et al. (1984).

Related literature top

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···OC hydrogen bonds, see: Taylor et al. (1984).

Experimental top

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.

Refinement top

All H atoms were placed in geometrically idealized positions and treated as riding on their parent atoms, with C—H = 0.95 - 1.00 Å, N—H = 0.88 Å and Uiso(H) = 1.2Ueq(C,N).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2010); cell refinement: CrysAlis PRO (Agilent, 2010); data reduction: CrysAlis PRO (Agilent, 2010); 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).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) with ellipsoids for non-H atoms shown at the 50% probability level.
Methyl 2-[(tert-butoxycarbonyl)amino]-3-(3-methyl-2-sulfanylidene- 2,3-dihydro-1H-imidazol-1-yl)propanoate top
Crystal data top
C13H21N3O4S-
Mr = 315.39Dx = 1.307 Mg m3
Monoclinic, P21/cMelting point: 379 K
Hall symbol: -P 2ybcCu Kα radiation, λ = 1.54178 Å
a = 8.7636 (1) ÅCell parameters from 9755 reflections
b = 19.1184 (2) Åθ = 4.6–71.5°
c = 9.6735 (2) ŵ = 1.97 mm1
β = 98.485 (1)°T = 110 K
V = 1603.02 (4) Å3Cube, colourless
Z = 40.60 × 0.50 × 0.30 mm
F(000) = 672
Data collection top
Agilent Xcalibur (Sapphire3, Gemini)
diffractometer
3093 independent reflections
Radiation source: fine-focus sealed tube2923 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.019
Detector resolution: 16.0690 pixels mm-1θmax = 71.6°, θmin = 4.6°
ω scansh = 109
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2010)
k = 2323
Tmin = 0.550, Tmax = 1.000l = 1011
12262 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.137H-atom parameters constrained
S = 1.05 w = 1/[σ2(Fo2) + (0.120P)2]
where P = (Fo2 + 2Fc2)/3
3093 reflections(Δ/σ)max = 0.001
190 parametersΔρmax = 0.39 e Å3
0 restraintsΔρmin = 0.53 e Å3
Crystal data top
C13H21N3O4SV = 1603.02 (4) Å3
Mr = 315.39Z = 4
Monoclinic, P21/cCu Kα radiation
a = 8.7636 (1) ŵ = 1.97 mm1
b = 19.1184 (2) ÅT = 110 K
c = 9.6735 (2) Å0.60 × 0.50 × 0.30 mm
β = 98.485 (1)°
Data collection top
Agilent Xcalibur (Sapphire3, Gemini)
diffractometer
3093 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2010)
2923 reflections with I > 2σ(I)
Tmin = 0.550, Tmax = 1.000Rint = 0.019
12262 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0360 restraints
wR(F2) = 0.137H-atom parameters constrained
S = 1.05Δρmax = 0.39 e Å3
3093 reflectionsΔρmin = 0.53 e Å3
190 parameters
Special details top

Experimental. CrysAlis PRO, Oxford Diffraction Ltd., Version 1.171.33.66 (release 28–04-2010 CrysAlis171. NET) (compiled Apr 28 2010,14:27:37) 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S0.73233 (4)0.397097 (16)0.68939 (3)0.01934 (17)
O11.13487 (11)0.21854 (5)0.76481 (9)0.0166 (2)
O21.21653 (11)0.16902 (5)0.97808 (10)0.0159 (2)
O31.39031 (11)0.39024 (5)0.96950 (12)0.0242 (3)
O41.20097 (10)0.46673 (5)0.89321 (11)0.0185 (2)
N10.65404 (12)0.27506 (6)0.81002 (12)0.0173 (3)
N20.85617 (12)0.32536 (6)0.92269 (12)0.0154 (3)
N31.18007 (12)0.28264 (5)0.96527 (11)0.0128 (3)
H3A1.21740.28161.05480.015*
C10.51211 (16)0.26296 (8)0.71401 (16)0.0257 (3)
H1A0.50020.29930.64170.039*
H1B0.42400.26450.76560.039*
H1C0.51670.21700.67010.039*
C20.74673 (14)0.33203 (7)0.80813 (13)0.0133 (3)
C30.70687 (16)0.23359 (8)0.92408 (16)0.0237 (3)
H3B0.66210.19090.94840.028*
C40.83277 (16)0.26432 (8)0.99458 (15)0.0222 (3)
H4A0.89380.24761.07730.027*
C50.98306 (14)0.37429 (7)0.95850 (14)0.0150 (3)
H5A1.00540.37941.06130.018*
H5B0.95310.42070.91800.018*
C61.12846 (13)0.34846 (6)0.90267 (13)0.0124 (3)
H6A1.10170.34120.79960.015*
C71.17322 (13)0.22218 (6)0.89111 (13)0.0117 (3)
C81.21603 (16)0.09602 (6)0.92637 (15)0.0155 (3)
C91.32792 (18)0.08866 (7)0.82123 (18)0.0255 (4)
H9A1.43120.10320.86460.038*
H9B1.29380.11830.73990.038*
H9C1.33090.03980.79140.038*
C101.27314 (18)0.05494 (7)1.05848 (16)0.0228 (3)
H10A1.19980.06021.12510.034*
H10B1.37430.07281.10040.034*
H10C1.28210.00541.03510.034*
C111.05181 (16)0.07481 (7)0.86891 (15)0.0215 (3)
H11A0.98590.08090.94150.032*
H11B1.05020.02570.83990.032*
H11C1.01350.10420.78820.032*
C121.25754 (15)0.40293 (6)0.92748 (14)0.0131 (3)
C131.31275 (16)0.52315 (7)0.90481 (17)0.0236 (3)
H13A1.26000.56730.87740.035*
H13B1.38970.51370.84320.035*
H13C1.36410.52661.00170.035*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S0.0231 (3)0.0120 (2)0.0207 (3)0.00343 (11)0.00411 (17)0.00477 (11)
O10.0231 (5)0.0148 (5)0.0116 (5)0.0038 (3)0.0021 (4)0.0014 (3)
O20.0216 (5)0.0103 (5)0.0145 (5)0.0009 (3)0.0014 (4)0.0014 (3)
O30.0128 (5)0.0217 (5)0.0364 (6)0.0026 (4)0.0020 (4)0.0038 (4)
O40.0153 (5)0.0110 (5)0.0281 (6)0.0027 (3)0.0001 (4)0.0003 (4)
N10.0109 (5)0.0163 (6)0.0243 (6)0.0033 (4)0.0010 (4)0.0038 (4)
N20.0115 (5)0.0145 (6)0.0198 (6)0.0016 (4)0.0011 (4)0.0042 (4)
N30.0147 (5)0.0121 (5)0.0108 (5)0.0002 (4)0.0008 (4)0.0005 (4)
C10.0149 (7)0.0260 (8)0.0345 (9)0.0096 (5)0.0017 (6)0.0024 (6)
C20.0113 (6)0.0110 (6)0.0178 (7)0.0000 (4)0.0031 (5)0.0004 (4)
C30.0182 (7)0.0200 (7)0.0335 (8)0.0042 (5)0.0055 (6)0.0119 (6)
C40.0175 (7)0.0226 (7)0.0264 (8)0.0010 (5)0.0031 (5)0.0125 (6)
C50.0114 (6)0.0156 (7)0.0173 (7)0.0015 (5)0.0002 (5)0.0019 (5)
C60.0116 (6)0.0129 (6)0.0122 (6)0.0015 (4)0.0002 (5)0.0007 (5)
C70.0078 (5)0.0122 (6)0.0155 (6)0.0027 (4)0.0022 (4)0.0004 (5)
C80.0208 (7)0.0078 (6)0.0179 (7)0.0042 (5)0.0028 (6)0.0017 (5)
C90.0321 (8)0.0118 (6)0.0366 (9)0.0032 (6)0.0184 (7)0.0024 (6)
C100.0297 (7)0.0129 (6)0.0242 (7)0.0019 (5)0.0014 (6)0.0028 (5)
C110.0231 (7)0.0198 (7)0.0200 (7)0.0105 (5)0.0019 (5)0.0023 (5)
C120.0139 (6)0.0127 (6)0.0126 (6)0.0018 (4)0.0010 (5)0.0008 (4)
C130.0189 (7)0.0137 (6)0.0369 (9)0.0064 (5)0.0004 (6)0.0010 (6)
Geometric parameters (Å, º) top
S—C21.6852 (13)C4—H4A0.9500
O1—C71.2204 (16)C5—C61.5370 (16)
O2—C71.3380 (16)C5—H5A0.9900
O2—C81.4825 (14)C5—H5B0.9900
O3—C121.1993 (17)C6—C121.5301 (16)
O4—C121.3398 (15)C6—H6A1.0000
O4—C131.4502 (16)C8—C111.5193 (18)
N1—C21.3605 (16)C8—C91.5199 (19)
N1—C31.3819 (18)C8—C101.5204 (19)
N1—C11.4567 (17)C9—H9A0.9800
N2—C21.3604 (17)C9—H9B0.9800
N2—C41.3890 (17)C9—H9C0.9800
N2—C51.4553 (16)C10—H10A0.9800
N3—C71.3571 (16)C10—H10B0.9800
N3—C61.4402 (16)C10—H10C0.9800
N3—H3A0.8800C11—H11A0.9800
C1—H1A0.9800C11—H11B0.9800
C1—H1B0.9800C11—H11C0.9800
C1—H1C0.9800C13—H13A0.9800
C3—C41.344 (2)C13—H13B0.9800
C3—H3B0.9500C13—H13C0.9800
C7—O2—C8121.10 (10)C5—C6—H6A108.1
C12—O4—C13115.91 (10)O1—C7—O2126.64 (11)
C2—N1—C3109.86 (11)O1—C7—N3124.20 (11)
C2—N1—C1125.02 (12)O2—C7—N3109.16 (11)
C3—N1—C1124.88 (12)O2—C8—C11109.28 (11)
C2—N2—C4110.38 (11)O2—C8—C9110.05 (10)
C2—N2—C5123.76 (11)C11—C8—C9113.60 (12)
C4—N2—C5125.80 (11)O2—C8—C10102.62 (11)
C7—N3—C6122.36 (10)C11—C8—C10110.26 (11)
C7—N3—H3A118.8C9—C8—C10110.47 (12)
C6—N3—H3A118.8C8—C9—H9A109.5
N1—C1—H1A109.5C8—C9—H9B109.5
N1—C1—H1B109.5H9A—C9—H9B109.5
H1A—C1—H1B109.5C8—C9—H9C109.5
N1—C1—H1C109.5H9A—C9—H9C109.5
H1A—C1—H1C109.5H9B—C9—H9C109.5
H1B—C1—H1C109.5C8—C10—H10A109.5
N2—C2—N1105.34 (11)C8—C10—H10B109.5
N2—C2—S126.68 (10)H10A—C10—H10B109.5
N1—C2—S127.98 (10)C8—C10—H10C109.5
C4—C3—N1107.92 (13)H10A—C10—H10C109.5
C4—C3—H3B126.0H10B—C10—H10C109.5
N1—C3—H3B126.0C8—C11—H11A109.5
C3—C4—N2106.51 (12)C8—C11—H11B109.5
C3—C4—H4A126.7H11A—C11—H11B109.5
N2—C4—H4A126.7C8—C11—H11C109.5
N2—C5—C6110.72 (10)H11A—C11—H11C109.5
N2—C5—H5A109.5H11B—C11—H11C109.5
C6—C5—H5A109.5O3—C12—O4124.96 (12)
N2—C5—H5B109.5O3—C12—C6124.98 (11)
C6—C5—H5B109.5O4—C12—C6110.05 (10)
H5A—C5—H5B108.1O4—C13—H13A109.5
N3—C6—C12110.47 (10)O4—C13—H13B109.5
N3—C6—C5110.99 (10)H13A—C13—H13B109.5
C12—C6—C5110.99 (10)O4—C13—H13C109.5
N3—C6—H6A108.1H13A—C13—H13C109.5
C12—C6—H6A108.1H13B—C13—H13C109.5
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N3—H3A···O1i0.882.252.9819 (14)140
Symmetry code: (i) x, y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC13H21N3O4S
Mr315.39
Crystal system, space groupMonoclinic, P21/c
Temperature (K)110
a, b, c (Å)8.7636 (1), 19.1184 (2), 9.6735 (2)
β (°) 98.485 (1)
V3)1603.02 (4)
Z4
Radiation typeCu Kα
µ (mm1)1.97
Crystal size (mm)0.60 × 0.50 × 0.30
Data collection
DiffractometerAgilent Xcalibur (Sapphire3, Gemini)
diffractometer
Absorption correctionMulti-scan
(CrysAlis PRO; Agilent, 2010)
Tmin, Tmax0.550, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections
12262, 3093, 2923
Rint0.019
(sin θ/λ)max1)0.615
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.137, 1.05
No. of reflections3093
No. of parameters190
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.39, 0.53

Computer programs: CrysAlis PRO (Agilent, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N3—H3A···O1i0.882.252.9819 (14)139.9
Symmetry code: (i) x, y+1/2, z+1/2.
 

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

First citationAgilent (2010). CrysAlis PRO. Agilent Technologies, Yarnton, England.
First citationKasraee, B. (2002). J. Invest. Dermatol. 118, 205–207.  Web of Science CrossRef PubMed CAS
First citationKasraee, B., Handjani, F., Parhizgar, A., Omrani, G. R., Fallahi, M. R., Amini, M., Nikbakhsh, M., Tran, C., Hügin, A., Sorg, O. & Saurat, J.-H. (2005). Dermatology, 211, 360–362.  Web of Science CrossRef PubMed CAS
First citationLiao, W. C., Wu, W. H., Tsai, P.-C., Wang, H.-F., Liu, Y.-H. & Chan, C.-F. (2012). Appl. Biochem. Biotechnol. 166, 259–267.  Web of Science CrossRef CAS PubMed
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationTaylor, R., Kennard, O. & Versichel, W. (1984). Acta Cryst. B40, 280–288.  CrossRef CAS Web of Science IUCr Journals

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