N-{4-[4-(4-Fluoro-phen-yl)-1-methyl-2-[(R)-methyl-sulfin-yl]-1H-imidazol-5-yl]-2-pyridyl}acetamide dihydrate.

In the crystal structure of the title compound, C(18)H(17)FN(4)O(2)S·2H(2)O, the organic mol-ecules are linked by inter-molecular O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds with the water mol-ecules, generating a three-dimensional network. The imidazole ring system forms a dihedral angle of 24.9 (2)° with the 4-fluoro-phenyl ring. The pyridine ring is oriented approximately perpendicular [72.24 (8)°] to the imidazole ring system.

Related literature

For general background and the biological activity of chiral sulfoxides and their potential use as therapeutic agents, see: Jia et al., (2004 ▶). Sulfoxide enanti­omers can differ in their pharmacodynamic and/or pharmacokinetic properties, see: Lu (2007 ▶). For the preparation of tri- and tetra­substituted 2-thio­imidazoles, see: Wagner et al. (2003 ▶); Laufer, Hauser, Domeyer et al. (2008 ▶); Laufer, Hauser & Liedtke (2008 ▶).

Experimental

Crystal data

C18H17FN4O2S·2H2O

M = 408.45

Orthorhombic,

a = 5.8178 (2) Å

b = 14.3233 (5) Å

c = 23.3694 (9) Å

V = 1947.37 (12) Å3

Z = 4

Mo Kα radiation

μ = 0.21 mm−1

T = 193 K

0.50 × 0.10 × 0.10 mm

Data collection

Bruker SMART APEXII diffractometer

10703 measured reflections

4628 independent reflections

2634 reflections with I > 2σ(I)

R int = 0.089

Refinement

R[F 2 > 2σ(F 2)] = 0.046

wR(F 2) = 0.099

S = 0.84

4628 reflections

256 parameters

H-atom parameters constrained

Δρmax = 0.27 e Å−3

Δρmin = −0.30 e Å−3

Absolute structure: Flack (1983 ▶), 1949 Friedel pairs

Flack parameter: −0.08 (11)

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809051873/nc2170sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809051873/nc2170Isup2.hkl

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

C18H17FN4O2S·2H2O	F(000) = 856
Mr = 408.45	Dx = 1.393 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1669 reflections
a = 5.8178 (2) Å	θ = 2.9–23.5°
b = 14.3233 (5) Å	µ = 0.21 mm−1
c = 23.3694 (9) Å	T = 193 K
V = 1947.37 (12) Å3	Needle, colourless
Z = 4	0.50 × 0.10 × 0.10 mm

Bruker SMART APEXII diffractometer	2634 reflections with I > 2σ(I)
Radiation source: sealed Tube	Rint = 0.089
graphite	θmax = 27.9°, θmin = 1.7°
CCD scan	h = −7→7
10703 measured reflections	k = −18→15
4628 independent reflections	l = −24→30

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.046	H-atom parameters constrained
wR(F2) = 0.099	w = 1/[σ2(Fo2) + (0.0293P)2] where P = (Fo2 + 2Fc2)/3
S = 0.84	(Δ/σ)max = 0.001
4628 reflections	Δρmax = 0.27 e Å−3
256 parameters	Δρmin = −0.29 e Å−3
0 restraints	Absolute structure: Flack (1983), 1949 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: −0.08 (11)

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
C1	−0.0028 (5)	0.38294 (18)	0.67677 (10)	0.0247 (6)
N2	0.0086 (5)	0.38684 (16)	0.73573 (9)	0.0301 (6)
C3	0.1670 (5)	0.44957 (18)	0.74681 (10)	0.0299 (7)
N4	0.2625 (4)	0.48701 (15)	0.69850 (7)	0.0276 (5)
C5	0.1496 (5)	0.44518 (18)	0.65318 (10)	0.0244 (6)
C6	−0.1622 (5)	0.31718 (18)	0.64897 (11)	0.0265 (7)
C7	−0.1212 (6)	0.2827 (2)	0.59361 (11)	0.0334 (7)
H7	0.0139	0.3008	0.5736	0.040*
C8	−0.2761 (6)	0.2227 (2)	0.56802 (13)	0.0406 (8)
H8	−0.2504	0.2003	0.5303	0.049*
C9	−0.4667 (6)	0.1961 (2)	0.59797 (14)	0.0428 (9)
C10	−0.5117 (6)	0.2250 (2)	0.65250 (13)	0.0391 (8)
H10	−0.6438	0.2036	0.6725	0.047*
C11	−0.3591 (5)	0.2864 (2)	0.67776 (12)	0.0326 (7)
H11	−0.3885	0.3082	0.7154	0.039*
F13	−0.6195 (4)	0.13680 (13)	0.57211 (9)	0.0687 (6)
S14	0.25518 (17)	0.48524 (5)	0.81652 (3)	0.0404 (2)
O15	0.3625 (4)	0.40219 (16)	0.84497 (7)	0.0490 (6)
C16	−0.0249 (7)	0.4982 (3)	0.84489 (11)	0.0636 (12)
H16C	−0.0151	0.5104	0.8861	0.095*
H16B	−0.1127	0.4408	0.8383	0.095*
H16A	−0.1020	0.5506	0.8260	0.095*
C17	0.4374 (6)	0.5604 (2)	0.69480 (12)	0.0439 (9)
H17A	0.4180	0.6041	0.7267	0.066*
H17B	0.4205	0.5940	0.6585	0.066*
H17C	0.5906	0.5321	0.6967	0.066*
C18	0.2057 (5)	0.47072 (17)	0.59317 (9)	0.0244 (6)
C19	0.4114 (5)	0.44302 (19)	0.56902 (11)	0.0285 (7)
H19	0.5209	0.4092	0.5909	0.034*
C20	0.4555 (6)	0.4653 (2)	0.51252 (11)	0.0331 (7)
H20	0.5962	0.4448	0.4961	0.040*
N21	0.3106 (4)	0.51404 (17)	0.47977 (8)	0.0294 (6)
C22	0.1152 (5)	0.54307 (19)	0.50371 (11)	0.0262 (7)
C23	0.0530 (5)	0.52212 (19)	0.56027 (10)	0.0264 (6)
H23	−0.0896	0.5426	0.5756	0.032*
N24	−0.0213 (4)	0.59582 (16)	0.46634 (9)	0.0314 (6)
H24	0.0221	0.5970	0.4291	0.047*
C25	−0.1937 (6)	0.65639 (19)	0.47982 (12)	0.0327 (7)
O26	−0.2713 (4)	0.66543 (13)	0.52821 (8)	0.0405 (5)
C27	−0.2867 (7)	0.7123 (2)	0.43046 (12)	0.0530 (10)
H27A	−0.2501	0.7784	0.4361	0.080*
H27C	−0.4538	0.7044	0.4284	0.080*
H27B	−0.2166	0.6904	0.3948	0.080*
O1L	0.2647 (6)	0.21319 (16)	0.85452 (9)	0.0726 (8)
H1L	0.2717	0.2057	0.8945	0.109*
H2L	0.2448	0.2723	0.8557	0.109*
O2L	0.0400 (5)	0.16661 (18)	0.75536 (11)	0.0795 (9)
H3L	0.1051	0.1806	0.7863	0.119*
H4L	−0.0357	0.2127	0.7435	0.119*

	U11	U22	U33	U12	U13	U23
C1	0.0296 (16)	0.0238 (15)	0.0207 (13)	0.0027 (13)	−0.0021 (14)	0.0000 (11)
N2	0.0400 (16)	0.0291 (14)	0.0211 (11)	−0.0024 (12)	−0.0021 (12)	0.0038 (10)
C3	0.0408 (19)	0.0302 (15)	0.0186 (13)	−0.0020 (14)	−0.0058 (14)	0.0009 (11)
N4	0.0324 (13)	0.0299 (12)	0.0206 (10)	−0.0038 (13)	−0.0037 (12)	0.0004 (9)
C5	0.0266 (17)	0.0261 (14)	0.0206 (13)	0.0042 (13)	−0.0028 (13)	0.0002 (11)
C6	0.0312 (19)	0.0238 (14)	0.0245 (13)	0.0029 (13)	−0.0061 (14)	0.0038 (11)
C7	0.0332 (18)	0.0328 (17)	0.0341 (16)	0.0031 (16)	−0.0017 (15)	−0.0034 (13)
C8	0.044 (2)	0.0349 (17)	0.0434 (16)	0.0021 (19)	−0.0093 (19)	−0.0141 (14)
C9	0.036 (2)	0.0325 (19)	0.060 (2)	−0.0051 (17)	−0.0175 (19)	−0.0050 (16)
C10	0.0320 (19)	0.0342 (18)	0.0512 (19)	−0.0045 (16)	−0.0054 (17)	0.0131 (15)
C11	0.0333 (18)	0.0325 (17)	0.0318 (15)	0.0013 (15)	−0.0020 (15)	0.0071 (13)
F13	0.0562 (14)	0.0548 (13)	0.0950 (15)	−0.0195 (12)	−0.0165 (14)	−0.0227 (12)
S14	0.0586 (5)	0.0411 (4)	0.0215 (3)	−0.0017 (5)	−0.0099 (4)	−0.0032 (3)
O15	0.0636 (17)	0.0592 (15)	0.0243 (10)	0.0236 (14)	−0.0124 (11)	−0.0030 (10)
C16	0.072 (3)	0.091 (3)	0.0272 (15)	0.030 (3)	−0.0050 (18)	−0.0117 (18)
C17	0.048 (2)	0.046 (2)	0.0385 (17)	−0.0163 (17)	−0.0022 (17)	0.0006 (14)
C18	0.0316 (18)	0.0237 (14)	0.0180 (12)	−0.0032 (14)	−0.0011 (12)	−0.0002 (10)
C19	0.0288 (17)	0.0322 (17)	0.0243 (14)	0.0034 (14)	−0.0031 (14)	0.0050 (12)
C20	0.0310 (18)	0.040 (2)	0.0288 (15)	0.0034 (15)	0.0038 (14)	0.0011 (13)
N21	0.0311 (15)	0.0318 (13)	0.0254 (11)	0.0066 (12)	0.0012 (11)	0.0013 (10)
C22	0.0313 (18)	0.0258 (16)	0.0214 (13)	−0.0029 (14)	−0.0005 (13)	−0.0007 (11)
C23	0.0289 (17)	0.0288 (16)	0.0214 (13)	0.0013 (14)	0.0018 (12)	−0.0020 (12)
N24	0.0385 (16)	0.0373 (15)	0.0185 (11)	0.0101 (14)	0.0004 (12)	0.0032 (10)
C25	0.037 (2)	0.0295 (16)	0.0318 (15)	0.0049 (15)	−0.0035 (15)	−0.0010 (12)
O26	0.0463 (14)	0.0462 (12)	0.0289 (10)	0.0108 (13)	0.0015 (12)	−0.0037 (9)
C27	0.065 (3)	0.052 (2)	0.0415 (17)	0.026 (2)	−0.006 (2)	0.0082 (15)
O1L	0.105 (2)	0.0615 (16)	0.0516 (13)	0.0245 (19)	0.0045 (17)	−0.0070 (12)
O2L	0.086 (2)	0.0676 (18)	0.0850 (18)	−0.0002 (17)	−0.0200 (19)	0.0271 (15)

C1—C5	1.373 (4)	C17—H17A	0.9800
C1—N2	1.380 (3)	C17—H17B	0.9800
C1—C6	1.473 (4)	C17—H17C	0.9800
N2—C3	1.313 (4)	C18—C19	1.381 (4)
C3—N4	1.368 (3)	C18—C23	1.386 (4)
C3—S14	1.783 (3)	C19—C20	1.382 (3)
N4—C5	1.383 (3)	C19—H19	0.9500
N4—C17	1.465 (4)	C20—N21	1.336 (3)
C5—C18	1.485 (3)	C20—H20	0.9500
C6—C11	1.400 (4)	N21—C22	1.333 (3)
C6—C7	1.405 (4)	C22—N24	1.402 (3)
C7—C8	1.382 (4)	C22—C23	1.403 (3)
C7—H7	0.9500	C23—H23	0.9500
C8—C9	1.365 (5)	N24—C25	1.363 (4)
C8—H8	0.9500	N24—H24	0.9072
C9—C10	1.365 (4)	C25—O26	1.224 (3)
C9—F13	1.370 (4)	C25—C27	1.505 (4)
C10—C11	1.382 (4)	C27—H27A	0.9800
C10—H10	0.9500	C27—H27C	0.9800
C11—H11	0.9500	C27—H27B	0.9800
S14—O15	1.499 (2)	O1L—H1L	0.9410
S14—C16	1.769 (4)	O1L—H2L	0.8545
C16—H16C	0.9800	O2L—H3L	0.8400
C16—H16B	0.9800	O2L—H4L	0.8400
C16—H16A	0.9800
C5—C1—N2	110.1 (2)	H16C—C16—H16A	109.5
C5—C1—C6	130.1 (2)	H16B—C16—H16A	109.5
N2—C1—C6	119.8 (2)	N4—C17—H17A	109.5
C3—N2—C1	105.0 (2)	N4—C17—H17B	109.5
N2—C3—N4	113.0 (2)	H17A—C17—H17B	109.5
N2—C3—S14	125.3 (2)	N4—C17—H17C	109.5
N4—C3—S14	121.7 (2)	H17A—C17—H17C	109.5
C3—N4—C5	105.6 (2)	H17B—C17—H17C	109.5
C3—N4—C17	127.7 (2)	C19—C18—C23	118.7 (2)
C5—N4—C17	126.5 (2)	C19—C18—C5	120.3 (2)
C1—C5—N4	106.3 (2)	C23—C18—C5	120.9 (2)
C1—C5—C18	132.9 (2)	C18—C19—C20	119.0 (3)
N4—C5—C18	120.8 (2)	C18—C19—H19	120.5
C11—C6—C7	118.1 (3)	C20—C19—H19	120.5
C11—C6—C1	120.3 (2)	N21—C20—C19	123.4 (3)
C7—C6—C1	121.6 (3)	N21—C20—H20	118.3
C8—C7—C6	120.4 (3)	C19—C20—H20	118.3
C8—C7—H7	119.8	C22—N21—C20	117.4 (2)
C6—C7—H7	119.8	N21—C22—N24	112.9 (2)
C9—C8—C7	118.8 (3)	N21—C22—C23	123.3 (3)
C9—C8—H8	120.6	N24—C22—C23	123.8 (3)
C7—C8—H8	120.6	C18—C23—C22	118.1 (3)
C10—C9—C8	123.4 (3)	C18—C23—H23	121.0
C10—C9—F13	118.4 (3)	C22—C23—H23	121.0
C8—C9—F13	118.3 (3)	C25—N24—C22	128.0 (2)
C9—C10—C11	117.9 (3)	C25—N24—H24	114.5
C9—C10—H10	121.0	C22—N24—H24	116.8
C11—C10—H10	121.0	O26—C25—N24	123.5 (2)
C10—C11—C6	121.4 (3)	O26—C25—C27	121.3 (3)
C10—C11—H11	119.3	N24—C25—C27	115.2 (3)
C6—C11—H11	119.3	C25—C27—H27A	109.5
O15—S14—C16	107.50 (16)	C25—C27—H27C	109.5
O15—S14—C3	107.32 (12)	H27A—C27—H27C	109.5
C16—S14—C3	96.18 (15)	C25—C27—H27B	109.5
S14—C16—H16C	109.5	H27A—C27—H27B	109.5
S14—C16—H16B	109.5	H27C—C27—H27B	109.5
H16C—C16—H16B	109.5	H1L—O1L—H2L	94.9
S14—C16—H16A	109.5	H3L—O2L—H4L	109.5
C5—C1—N2—C3	−0.7 (3)	F13—C9—C10—C11	−178.6 (3)
C6—C1—N2—C3	178.7 (3)	C9—C10—C11—C6	−1.1 (4)
C1—N2—C3—N4	−0.4 (3)	C7—C6—C11—C10	−0.9 (4)
C1—N2—C3—S14	179.4 (2)	C1—C6—C11—C10	179.8 (3)
N2—C3—N4—C5	1.4 (3)	N2—C3—S14—O15	64.5 (3)
S14—C3—N4—C5	−178.5 (2)	N4—C3—S14—O15	−115.7 (2)
N2—C3—N4—C17	177.9 (3)	N2—C3—S14—C16	−46.0 (3)
S14—C3—N4—C17	−2.0 (4)	N4—C3—S14—C16	133.8 (3)
N2—C1—C5—N4	1.5 (3)	C1—C5—C18—C19	−107.8 (4)
C6—C1—C5—N4	−177.8 (3)	N4—C5—C18—C19	71.7 (3)
N2—C1—C5—C18	−178.9 (3)	C1—C5—C18—C23	71.8 (4)
C6—C1—C5—C18	1.8 (5)	N4—C5—C18—C23	−108.7 (3)
C3—N4—C5—C1	−1.7 (3)	C23—C18—C19—C20	−1.7 (4)
C17—N4—C5—C1	−178.2 (3)	C5—C18—C19—C20	177.9 (3)
C3—N4—C5—C18	178.7 (2)	C18—C19—C20—N21	1.2 (4)
C17—N4—C5—C18	2.1 (4)	C19—C20—N21—C22	0.8 (4)
C5—C1—C6—C11	−155.5 (3)	C20—N21—C22—N24	178.2 (2)
N2—C1—C6—C11	25.2 (4)	C20—N21—C22—C23	−2.3 (4)
C5—C1—C6—C7	25.2 (5)	C19—C18—C23—C22	0.3 (4)
N2—C1—C6—C7	−154.0 (3)	C5—C18—C23—C22	−179.3 (2)
C11—C6—C7—C8	2.1 (4)	N21—C22—C23—C18	1.8 (4)
C1—C6—C7—C8	−178.6 (3)	N24—C22—C23—C18	−178.8 (3)
C6—C7—C8—C9	−1.3 (4)	N21—C22—N24—C25	−160.2 (3)
C7—C8—C9—C10	−0.8 (5)	C23—C22—N24—C25	20.3 (4)
C7—C8—C9—F13	179.8 (3)	C22—N24—C25—O26	−8.5 (5)
C8—C9—C10—C11	2.0 (5)	C22—N24—C25—C27	172.0 (3)

D—H···A	D—H	H···A	D···A	D—H···A
N24—H24···O15i	0.91	2.08	2.983 (3)	177
O1L—H2L···O15	0.85	2.00	2.775 (3)	151
O1L—H1L···O26ii	0.94	1.90	2.825 (3)	169
O2L—H3L···O1L	0.84	1.90	2.743 (4)	177
O2L—H4L···N2	0.84	2.51	3.193 (3)	138

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N24—H24⋯O15i	0.91	2.08	2.983 (3)	177
O1L—H1L⋯O26ii	0.94	1.90	2.825 (3)	169
O1L—H2L⋯O15	0.85	2.00	2.775 (3)	151
O2L—H3L⋯O1L	0.84	1.90	2.743 (4)	177
O2L—H4L⋯N2	0.84	2.51	3.193 (3)	138

Symmetry codes: (i) ; (ii) .