2-(2,4-Di­chloro­phenyl)-5-fluoro-6-morpholin-4-yl-1H-benz­imidazole monohydrate

The crystal structure of the title compound, C₁₇H₁₄Cl₂FN₃O·H₂O, is stabilized by hydrogen bonds. The morpholine ring exhibits a typical chair conformation, while the benz­imidazole system is planar.

Key indicators

• Single-crystal X-ray study
• T = 295 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.038
• wR factor = 0.106
• Data-to-parameter ratio = 14.3

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

General Notes



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S1. Comment

The benzimidazole nucleus, which is a useful structure for further molecular exploration and for the development of new pharmaceutical compounds, has received much attention in recent years (Mann et al., 2001; Nakano et al., 2000). Owing to the versatility of this heterocycle, we are focusing our research efforts on new and potent benzimidazole derivatives. In our previous studies we described the synthesis and antimicrobial activities of some benzimidazole derivatives (Göker et al., 2001; Kuş et al., 2001). 2-(substituted phenyl)- benzimidazoles have different pharmaceutical activities such as antibacterial, antiviral, antitumoral and anti-inflammatory (Coburn et al., 1987; Roth et al., 1997; Chen et al., 1993; Denny et al., 1993; Evans et al., 1996).

To evaluate their antimicrobial activities, we synthesized 2-(2,4-Dichlorophenyl)-5-fluoro-6-morpholin-4-yl-1H-benzimidazole and its analogues. The synthesis and physical and spectroscopic data of this compound, which has a substituted phenyl ring at the 2 position of the benzimidazole nucleus, has been reported by us (Kuş, 2002). In this research, the X-ray structure of its monohydrate, (I), was determined in order to establish its conformation.

The intramolecular bond distances and angles (Table 1) for the benzimidazole moiety of (I) are in good agreement with those observed in other benzimidazole derivatives (Göker et al., 1995; Özbey et al., 1998; Kendi et al., 1999; Vasudevan et al., 1994; Balasubramanian et al., 1996). The bond lengths C15—Cl1 and C17—Cl2 (Table 1) are within the expected range (Allen et al., 1987).

As expected, the benzimidazole ring system is essentially planar [maximum deviation 0.017 (3) Å for C9], with a dihedral angle of 1.54 (9) Å between the imidazole and the benzene ring planes. The F atom lies −0.077 (2) Å from the least-squares plane defined by all the atoms of the two fused rings. In the molecule, the benzimidazole system is coplanar with the phenyl substituent owing to the hydrogen bonding between the imidazole N atoms and the chlorine and one of the carbon atoms of the phenyl moiety (Table 2). The dihedral angle between the best planes of these rings is 0.15 (7)°, so the structure is almost planar except for the morpholin ring, as shown in Fig. 1. The dichlorophenyl ring is planar and the Cl1 atom is situated 0.0240 (9) Å above this plane.

The morpholin ring deviates from planarity, with atoms N2 and O1 displaced from the C10/C11/C12/C13 mean plane by 0.689 (2) and −0.645 (2) Å, respectively. The dihedral angle between the best planes of the morpholin ring and the benzimidazole ring is 40.8 (1)°. The puckering parameters (Cremer & Pople, 1975) of this ring are Q=0.581 (2) Å, θ=177.1 (3)° and ϕ=-43 (5)°, thus the morpholin ring adopts a chair conformation.

The crystal structure of the title compound is stabilized by intra- and intermolecular hydrogen bonds (Table 2, Fig. 2).

S2. Experimental

In order to obtain 2-(2,4-Dichlorophenyl)-5-fluoro-6-morpholin-4-yl-1H-benzimidazole (Kuş, 2002), to a suspension of 4-fluoro-5-morpholin-4-yl-benzene-1,2-diamine (Sanna et al., 1998) (0,211 g, 1 mmol) in DMF (5 ml), the sodium metabisulfite adduct of 2,4-dichlorobenzaldehyde (0.191 g, 1 mmol) was added and the mixture was heated under a nitrogen atmosphere for 4 h at 333 K. Water was added to the reaction medium and the solid product obtained was collected by filtration and washed with water. The residue was chromatographed [EtOAc: n-hexane (1:2)] and recrystallized from ethanol, affording 0,311 mg (85%) of (I); m.p. 485–487 K. The assigned structure was substantiated by IR, ¹H NMR and MS data.

S3. Refinement

The H atoms of N1 and water molecule were located from a difference Fourier map and refined freely. The other H atoms were positioned geometrically at distances 0.93 and 0.97 Å for methylene and aromatic H atoms, respectively, and refined riding on their parent atoms.

Computing details

Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP (Johnson, 1965); software used to prepare material for publication: PLATON (Spek, 2000).

Figures

	Fig. 1. ORTEP (Johnson, 1965) drawing of the asymmetric unit of the title compound with the atomic numbering scheme. The displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as small circles of arbitrary radii.
	Fig. 2. The intermolecular hydrogen bonds in (I).

(I)

Crystal data

C17H14Cl2FN3O·H2O	Dx = 1.519 Mg m^−3
Mr = 384.23	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 25 reflections
a = 7.4455 (7) Å	θ = 10.2–18.0°
b = 15.310 (3) Å	µ = 0.41 mm^−1
c = 29.487 (3) Å	T = 295 K
V = 3361.2 (8) Å^3	Prism, light yellow
Z = 8	0.48 × 0.36 × 0.24 mm
F(000) = 1584

Data collection

Enraf-Nonius TurboCAD4 diffractometer	Rint = 0.079
non–profiled ω scans	θmax = 26.3°, θmin = 2.7°
Absorption correction: psi scan (north et al., 1968) ?	h = 0→9
Tmin = 0.826, Tmax = 0.907	k = 0→19
3893 measured reflections	l = 0→36
3403 independent reflections	3 standard reflections every 120 min
2174 reflections with I > 2σ(I)	intensity decay: 4%

Refinement

Refinement on F^2	5 restraints
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.038	w = 1/[σ^2(Fo^2) + (0.0454P)^2 + 1.0249P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.106	(Δ/σ)max < 0.001
S = 1.02	Δρmax = 0.23 e Å^−3
3403 reflections	Δρmin = −0.32 e Å^−3
238 parameters

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O2	0.4415 (3)	−0.16610 (12)	0.09903 (7)	0.0535 (5)
H1	0.133 (4)	0.2013 (13)	0.1179 (9)	0.056 (8)*
H21	0.382 (4)	−0.1131 (15)	0.1033 (10)	0.068 (10)*
H22	0.572 (3)	−0.170 (3)	0.0908 (15)	0.150 (19)*
C2	0.2107 (3)	0.07292 (15)	0.13048 (8)	0.0339 (5)
C4	0.2742 (4)	0.00320 (17)	0.01776 (8)	0.0454 (7)
H4	0.3125	−0.0544	0.0154	0.054*
C5	0.2488 (4)	0.05422 (16)	−0.01928 (8)	0.0419 (6)
C6	0.1896 (3)	0.14190 (15)	−0.01880 (8)	0.0346 (5)
C7	0.1546 (3)	0.17945 (15)	0.02315 (8)	0.0338 (5)
H7	0.1151	0.2369	0.0255	0.041*
C8	0.1809 (3)	0.12803 (14)	0.06172 (8)	0.0325 (5)
C9	0.2396 (3)	0.04220 (16)	0.05994 (8)	0.0363 (6)
C10	0.0377 (4)	0.15492 (17)	−0.09148 (9)	0.0479 (7)
H10A	−0.0798	0.1671	−0.0787	0.058*
H10B	0.0494	0.0922	−0.0951	0.058*
C11	0.0566 (4)	0.19969 (18)	−0.13705 (9)	0.0532 (7)
H11A	0.1737	0.1864	−0.1497	0.064*
H11B	−0.0338	0.1772	−0.1576	0.064*
C12	0.1692 (4)	0.32403 (17)	−0.10326 (9)	0.0504 (7)
H12A	0.1539	0.3867	−0.1002	0.061*
H12B	0.2872	0.3135	−0.1161	0.061*
C13	0.1595 (4)	0.28246 (16)	−0.05668 (8)	0.0410 (6)
H13A	0.2541	0.3057	−0.0376	0.049*
H13B	0.045	0.296	−0.0427	0.049*
C14	0.2112 (3)	0.06133 (16)	0.18017 (8)	0.0356 (6)
C15	0.1623 (4)	0.12234 (16)	0.21325 (8)	0.0387 (6)
C16	0.1670 (4)	0.10329 (16)	0.25924 (8)	0.0430 (6)
H16	0.134	0.1451	0.2806	0.052*
C17	0.2212 (4)	0.02148 (17)	0.27270 (8)	0.0449 (7)
C18	0.2695 (4)	−0.04135 (17)	0.24157 (9)	0.0497 (7)
H18	0.3052	−0.0966	0.251	0.06*
C19	0.2638 (4)	−0.02068 (16)	0.19617 (9)	0.0443 (6)
H19	0.2964	−0.0632	0.1752	0.053*
Cl1	0.08997 (13)	0.22705 (4)	0.19919 (2)	0.0626 (3)
Cl2	0.22726 (12)	−0.00354 (5)	0.32997 (2)	0.0651 (3)
F1	0.2899 (3)	0.01926 (10)	−0.06064 (5)	0.0644 (5)
N1	0.1615 (3)	0.14605 (13)	0.10721 (7)	0.0351 (5)
N2	0.1796 (3)	0.18785 (12)	−0.06074 (6)	0.0341 (5)
N3	0.2587 (3)	0.00853 (12)	0.10326 (7)	0.0389 (5)
O1	0.0371 (3)	0.29124 (12)	−0.13328 (6)	0.0526 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O2	0.0563 (14)	0.0337 (10)	0.0704 (13)	−0.0020 (10)	0.0069 (11)	−0.0007 (9)
C2	0.0351 (14)	0.0306 (12)	0.0359 (13)	−0.0041 (11)	0.0000 (10)	−0.0030 (10)
C4	0.0626 (19)	0.0325 (13)	0.0410 (14)	0.0075 (13)	0.0058 (13)	−0.0048 (11)
C5	0.0594 (17)	0.0363 (13)	0.0300 (12)	0.0041 (12)	0.0067 (12)	−0.0073 (10)
C6	0.0352 (14)	0.0330 (12)	0.0357 (12)	−0.0021 (11)	0.0020 (11)	0.0005 (10)
C7	0.0363 (14)	0.0294 (12)	0.0359 (12)	0.0021 (11)	0.0015 (11)	−0.0027 (10)
C8	0.0327 (13)	0.0299 (12)	0.0350 (12)	−0.0022 (10)	0.0013 (10)	−0.0044 (10)
C9	0.0423 (14)	0.0321 (12)	0.0344 (12)	−0.0014 (11)	0.0021 (11)	−0.0017 (10)
C10	0.0517 (17)	0.0462 (15)	0.0458 (15)	−0.0092 (14)	−0.0077 (13)	−0.0026 (12)
C11	0.068 (2)	0.0495 (16)	0.0417 (15)	−0.0008 (15)	−0.0164 (15)	−0.0018 (12)
C12	0.072 (2)	0.0354 (14)	0.0442 (15)	0.0002 (14)	−0.0039 (14)	0.0020 (12)
C13	0.0496 (16)	0.0326 (12)	0.0409 (14)	0.0045 (12)	−0.0028 (12)	−0.0045 (11)
C14	0.0376 (15)	0.0333 (13)	0.0360 (13)	−0.0047 (11)	−0.0001 (11)	−0.0012 (10)
C15	0.0455 (15)	0.0320 (13)	0.0386 (14)	0.0008 (12)	0.0000 (12)	−0.0002 (10)
C16	0.0531 (17)	0.0391 (13)	0.0369 (15)	0.0019 (12)	0.0018 (13)	−0.0053 (11)
C17	0.0539 (18)	0.0473 (16)	0.0337 (14)	0.0013 (13)	0.0002 (12)	0.0019 (11)
C18	0.071 (2)	0.0391 (14)	0.0393 (15)	0.0096 (14)	−0.0006 (14)	0.0016 (11)
C19	0.0597 (18)	0.0343 (13)	0.0389 (14)	0.0044 (13)	0.0030 (13)	−0.0052 (11)
Cl1	0.1075 (7)	0.0377 (4)	0.0426 (4)	0.0179 (4)	0.0048 (4)	−0.0013 (3)
Cl2	0.1003 (7)	0.0616 (5)	0.0335 (3)	0.0178 (5)	−0.0003 (4)	0.0039 (3)
F1	0.1121 (16)	0.0465 (10)	0.0345 (8)	0.0205 (9)	0.0113 (9)	−0.0066 (7)
N1	0.0418 (12)	0.0311 (11)	0.0324 (11)	0.0014 (10)	0.0018 (9)	−0.0032 (9)
N2	0.0378 (12)	0.0305 (10)	0.0339 (10)	−0.0014 (9)	−0.0006 (9)	−0.0019 (8)
N3	0.0485 (13)	0.0323 (11)	0.0360 (11)	−0.0002 (10)	0.0022 (10)	−0.0010 (9)
O1	0.0608 (13)	0.0492 (11)	0.0479 (11)	0.0115 (10)	−0.0109 (10)	0.0004 (8)

Geometric parameters (Å, º)

O2—H21	0.935 (18)	C11—H11A	0.97
O2—H22	1.004 (18)	C11—H11B	0.97
C2—N3	1.321 (3)	C12—O1	1.415 (3)
C2—N1	1.363 (3)	C12—C13	1.516 (3)
C2—C14	1.476 (3)	C12—H12A	0.97
C4—C5	1.356 (4)	C12—H12B	0.97
C4—C9	1.404 (3)	C13—N2	1.461 (3)
C4—H4	0.93	C13—H13A	0.97
C5—F1	1.367 (3)	C13—H13B	0.97
C5—C6	1.413 (3)	C14—C19	1.397 (4)
C6—C7	1.389 (3)	C14—C15	1.399 (3)
C6—N2	1.425 (3)	C15—C16	1.387 (3)
C7—C8	1.397 (3)	C15—Cl1	1.741 (3)
C7—H7	0.93	C16—C17	1.375 (4)
C8—N1	1.377 (3)	C16—H16	0.93
C8—C9	1.386 (3)	C17—C18	1.377 (4)
C9—N3	1.385 (3)	C17—Cl2	1.732 (2)
C10—N2	1.481 (3)	C18—C19	1.376 (4)
C10—C11	1.515 (4)	C18—H18	0.93
C10—H10A	0.97	C19—H19	0.93
C10—H10B	0.97	N1—H1	0.927 (18)
C11—O1	1.413 (3)
H21—O2—H22	123 (3)	C13—C12—H12A	109.1
N3—C2—N1	112.3 (2)	O1—C12—H12B	109.1
N3—C2—C14	120.9 (2)	C13—C12—H12B	109.1
N1—C2—C14	126.8 (2)	H12A—C12—H12B	107.8
C5—C4—C9	116.3 (2)	N2—C13—C12	109.7 (2)
C5—C4—H4	121.9	N2—C13—H13A	109.7
C9—C4—H4	121.9	C12—C13—H13A	109.7
C4—C5—F1	117.5 (2)	N2—C13—H13B	109.7
C4—C5—C6	125.6 (2)	C12—C13—H13B	109.7
F1—C5—C6	116.8 (2)	H13A—C13—H13B	108.2
C7—C6—C5	117.4 (2)	C19—C14—C15	115.9 (2)
C7—C6—N2	124.0 (2)	C19—C14—C2	116.4 (2)
C5—C6—N2	118.5 (2)	C15—C14—C2	127.7 (2)
C6—C7—C8	117.8 (2)	C16—C15—C14	122.3 (2)
C6—C7—H7	121.1	C16—C15—Cl1	115.72 (19)
C8—C7—H7	121.1	C14—C15—Cl1	121.95 (19)
N1—C8—C9	105.1 (2)	C17—C16—C15	118.8 (2)
N1—C8—C7	131.7 (2)	C17—C16—H16	120.6
C9—C8—C7	123.2 (2)	C15—C16—H16	120.6
N3—C9—C8	110.5 (2)	C16—C17—C18	121.4 (2)
N3—C9—C4	129.8 (2)	C16—C17—Cl2	119.4 (2)
C8—C9—C4	119.7 (2)	C18—C17—Cl2	119.2 (2)
N2—C10—C11	108.8 (2)	C19—C18—C17	118.7 (2)
N2—C10—H10A	109.9	C19—C18—H18	120.7
C11—C10—H10A	109.9	C17—C18—H18	120.7
N2—C10—H10B	109.9	C18—C19—C14	122.9 (2)
C11—C10—H10B	109.9	C18—C19—H19	118.5
H10A—C10—H10B	108.3	C14—C19—H19	118.5
O1—C11—C10	111.7 (2)	C2—N1—C8	107.31 (19)
O1—C11—H11A	109.3	C2—N1—H1	129.8 (17)
C10—C11—H11A	109.3	C8—N1—H1	122.4 (17)
O1—C11—H11B	109.3	C6—N2—C13	115.07 (18)
C10—C11—H11B	109.3	C6—N2—C10	113.62 (19)
H11A—C11—H11B	107.9	C13—N2—C10	108.3 (2)
O1—C12—C13	112.6 (2)	C2—N3—C9	104.77 (19)
O1—C12—H12A	109.1	C11—O1—C12	109.3 (2)
C9—C4—C5—F1	176.9 (2)	Cl1—C15—C16—C17	179.4 (2)
C9—C4—C5—C6	−0.6 (4)	C15—C16—C17—C18	−0.4 (4)
C4—C5—C6—C7	0.1 (4)	C15—C16—C17—Cl2	−179.8 (2)
F1—C5—C6—C7	−177.3 (2)	C16—C17—C18—C19	0.4 (4)
C4—C5—C6—N2	176.5 (3)	Cl2—C17—C18—C19	179.9 (2)
F1—C5—C6—N2	−1.0 (4)	C17—C18—C19—C14	0.0 (4)
C5—C6—C7—C8	0.2 (4)	C15—C14—C19—C18	−0.5 (4)
N2—C6—C7—C8	−176.0 (2)	C2—C14—C19—C18	−179.5 (2)
C6—C7—C8—N1	178.8 (2)	N3—C2—N1—C8	−0.7 (3)
C6—C7—C8—C9	0.0 (4)	C14—C2—N1—C8	−179.7 (2)
N1—C8—C9—N3	−0.9 (3)	C9—C8—N1—C2	1.0 (3)
C7—C8—C9—N3	178.1 (2)	C7—C8—N1—C2	−178.0 (3)
N1—C8—C9—C4	−179.5 (2)	C7—C6—N2—C13	10.1 (3)
C7—C8—C9—C4	−0.5 (4)	C5—C6—N2—C13	−166.0 (2)
C5—C4—C9—N3	−177.6 (3)	C7—C6—N2—C10	−115.6 (3)
C5—C4—C9—C8	0.7 (4)	C5—C6—N2—C10	68.3 (3)
N2—C10—C11—O1	−60.6 (3)	C12—C13—N2—C6	174.4 (2)
O1—C12—C13—N2	57.9 (3)	C12—C13—N2—C10	−57.2 (3)
N3—C2—C14—C19	−0.3 (4)	C11—C10—N2—C6	−172.2 (2)
N1—C2—C14—C19	178.6 (2)	C11—C10—N2—C13	58.6 (3)
N3—C2—C14—C15	−179.2 (2)	N1—C2—N3—C9	0.1 (3)
N1—C2—C14—C15	−0.2 (4)	C14—C2—N3—C9	179.2 (2)
C19—C14—C15—C16	0.6 (4)	C8—C9—N3—C2	0.5 (3)
C2—C14—C15—C16	179.4 (3)	C4—C9—N3—C2	178.9 (3)
C19—C14—C15—Cl1	−179.0 (2)	C10—C11—O1—C12	59.0 (3)
C2—C14—C15—Cl1	−0.1 (4)	C13—C12—O1—C11	−57.6 (3)
C14—C15—C16—C17	−0.1 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···Cl1	0.93 (2)	2.45 (3)	3.029 (2)	121 (2)
C19—H19···N3	0.93	2.41	2.776 (3)	104
C10—H10B···F1	0.97	2.34	2.944 (3)	120
N1—H1···O2^i	0.93 (2)	2.18 (2)	2.986 (3)	145 (2)
O2—H21···N3	0.93 (2)	2.07 (2)	3.002 (3)	172 (3)
O2—H22···N2^ii	1.00 (2)	2.07 (3)	3.057 (3)	168 (4)
C12—H12A···F1^i	0.97	2.38	3.257 (3)	150
C12—H12A···Cl2^iii	0.97	2.78	3.408 (3)	123

Symmetry codes: (i) −x+1/2, y+1/2, z; (ii) −x+1, −y, −z; (iii) x, −y+1/2, z−1/2.