2-Chloro­methyl-1-methyl-1,3-benzimidazole

Han, J.; Zhang, J.; Yang, Q.; Zhao, M.; Fan, G.

doi:10.1107/S1600536811028376

organic compounds

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ISSN: 2056-9890

Volume 67| Part 8| August 2011| Page o2104

doi:10.1107/S1600536811028376

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2-Chloromethyl-1-methyl-1,3-benzimidazole

Jie Han,^a Jun Zhang,^a Qi Yang,^a Ming-gao Zhao ^a ^* and Guang Fan ^b

^aDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Chang-le West Road 17, Xi'an 710032, Shaanxi, People's Republic of China, and ^bCollege of Chemistry & Chemical Engineering, Xianyang Normal University, Xianyang 712000, Shaanxi, People's Republic of China
^*Correspondence e-mail: minggao@fmmu.edu.cn

(Received 7 July 2011; accepted 15 July 2011; online 23 July 2011)

The title compound, C₉H₉ClN₂, was prepared from the reaction of N-methylbenzene-1,2-diamine and 2-chloroacetic acid in boiling 6 M hydrochloric acid. The benzimidazole unit is approximately planar, the largest deviation from the mean plane being 0.008 (1) Å. The Cl atom is displaced by 1.667 (2) Å from this plane. The methyl group is statistically disordered with equal occupancy.

Related literature

For the biological activity of benzimidazoles, see: Refaat (2010 ); Laryea et al. (2010 ); Horton et al. (2003 ); Ries et al. (2003 ); Spasov et al. (1999 ); Matsui et al. (1994 ); Porcari et al. (1998 ); Rath et al. (1997 ); Migawa et al. (1998 ). For a description of the Cambridge Structural Database, see: Allen (2002 ).

Experimental

Crystal data

C₉H₉ClN₂
M_r = 180.63
Triclinic, $[P \overline 1]$
a = 6.607 (2) Å
b = 8.168 (2) Å
c = 8.925 (3) Å
α = 84.566 (3)°
β = 79.682 (4)°
γ = 68.134 (4)°
V = 439.6 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.38 mm⁻¹
T = 296 K
0.37 × 0.29 × 0.18 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2002 ) T_min = 0.874, T_max = 0.937
2191 measured reflections
1523 independent reflections
1361 reflections with I > 2σ(I)
R_int = 0.018

Refinement

R[F² > 2σ(F²)] = 0.042
wR(F²) = 0.122
S = 1.06
1523 reflections
109 parameters
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.32 e Å⁻³

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ) and ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811028376/dn2705sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811028376/dn2705Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811028376/dn2705Isup3.cml

checkCIF report

Comment top

Benzimidazole and its derivatives are present in various bioactive compounds possessing antiparasitic, antimicrobial, and antifungal properties (Refaat, 2010; Laryea et al., 2010; Horton et al., 2003; Ries et al., 2003; Spasov et al., 1999; Matsui et al. 1994). They also play very important role in the synthesis of many natural products and synthetic drugs. Compounds possessing the benzimidazole moiety express significant activity against several viruses such as HIV (Porcari, et al., 1998; Rath, et al., 1997), Herpes (HSV-1) (Migawa, et al., 1998), human cytomegalovirus (HCMV) and influenza. As a part of our ongoing investigations of benzimidazole derivatives, the title compound was synthesized and its crystal structure is reported herein.

The two fused rings forming the benzimidazole moiety are planar with the largest deviation from the mean plane being 0.008 (1)Å. The Cl atom is out of this plane by -1.667 (2)Å (Fig. 1). The methyl group is statistically disordered. The distances and angles within the methyl-benzimidazole agree with the values reported in the literature (43 hits found in the Cambridge Structural Database, Conquest, version 1.13; Allen, 2002).

The packing is only stabilized by electrostatic and van der Waals interactions.

Related literature top

For the biological activity of benzimidazoles, see: Refaat (2010); Laryea et al. (2010) ; Horton et al. (2003); Ries et al. (2003); Spasov et al. (1999); Matsui et al. (1994); Porcari et al. (1998); Rath et al. (1997); Migawa et al. (1998). For a description of the Cambridge Structural Database, see: Allen (2002).

Experimental top

For the preparation of the title compound N-methylbenzene-1,2-diamine (5.0 mmol) and 2-chloroacetic acid(6.0 mmol) was dissolved in 6 N hydrochloric acid (30.0 ml) and refluxed for 6 h. The reaction mixture was cooled in to room temperature, then neutralized with aqueous sodium hydroxide. The precipitate was filtered off and washed with cold water. The crude product was crystallized from ethanol to give white block-like crystals of the title compound.

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

Fig. 1. The asymmetric unit of (1) with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radii.

2-Chloromethyl-1-methyl-1,3-benzimidazole top

Crystal data top

C₉H₉ClN₂	Z = 2
M_r = 180.63	F(000) = 188
Triclinic, P1	D_x = 1.365 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.607 (2) Å	Cell parameters from 2191 reflections
b = 8.168 (2) Å	θ = 2.3–25.1°
c = 8.925 (3) Å	µ = 0.38 mm⁻¹
α = 84.566 (3)°	T = 296 K
β = 79.682 (4)°	Block, white
γ = 68.134 (4)°	0.37 × 0.29 × 0.18 mm
V = 439.6 (2) Å³

Data collection top

Bruker SMART APEX CCD diffractometer	1523 independent reflections
Radiation source: fine-focus sealed tube	1361 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.018
ϕ and ω scans	θ_max = 25.1°, θ_min = 2.3°
Absorption correction: multi-scan (SADABS; Bruker, 2002)	h = −7→5
T_min = 0.874, T_max = 0.937	k = −9→9
2191 measured reflections	l = −10→10

Refinement top

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)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.122	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.0552P)² + 0.1656P] where P = (F_o² + 2F_c²)/3
1523 reflections	(Δ/σ)_max < 0.001
109 parameters	Δρ_max = 0.20 e Å⁻³
0 restraints	Δρ_min = −0.32 e Å⁻³

Crystal data top

C₉H₉ClN₂	γ = 68.134 (4)°
M_r = 180.63	V = 439.6 (2) Å³
Triclinic, P1	Z = 2
a = 6.607 (2) Å	Mo Kα radiation
b = 8.168 (2) Å	µ = 0.38 mm⁻¹
c = 8.925 (3) Å	T = 296 K
α = 84.566 (3)°	0.37 × 0.29 × 0.18 mm
β = 79.682 (4)°

Data collection top

Bruker SMART APEX CCD diffractometer	1523 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2002)	1361 reflections with I > 2σ(I)
T_min = 0.874, T_max = 0.937	R_int = 0.018
2191 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.042	0 restraints
wR(F²) = 0.122	H-atom parameters constrained
S = 1.06	Δρ_max = 0.20 e Å⁻³
1523 reflections	Δρ_min = −0.32 e Å⁻³
109 parameters

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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

	x	y	z	U_iso*/U_eq	Occ. (<1)
C1	0.2259 (4)	0.4372 (3)	0.6995 (2)	0.0610 (6)
H1A	0.3424	0.4781	0.7109	0.073*
H1B	0.0985	0.5393	0.6790	0.073*
C2	0.1665 (3)	0.3458 (2)	0.8432 (2)	0.0498 (5)
C3	−0.2214 (4)	0.3954 (3)	0.8004 (3)	0.0666 (6)
H3A	−0.3405	0.3638	0.8563	0.100*	0.50
H3B	−0.1788	0.3444	0.7017	0.100*	0.50
H3C	−0.2683	0.5215	0.7888	0.100*	0.50
H3D	−0.1846	0.4560	0.7082	0.100*	0.50
H3E	−0.3463	0.4754	0.8628	0.100*	0.50
H3F	−0.2568	0.2983	0.7757	0.100*	0.50
C4	−0.0294 (3)	0.2393 (2)	1.0212 (2)	0.0488 (5)
C5	−0.1859 (4)	0.1843 (3)	1.1144 (3)	0.0600 (6)
H5	−0.3242	0.2069	1.0885	0.072*
C6	−0.1250 (4)	0.0947 (3)	1.2471 (3)	0.0675 (6)
H6	−0.2258	0.0574	1.3137	0.081*
C7	0.0842 (4)	0.0581 (3)	1.2848 (3)	0.0673 (6)
H7	0.1198	−0.0041	1.3751	0.081*
C8	0.2384 (4)	0.1119 (3)	1.1915 (2)	0.0605 (6)
H8	0.3773	0.0871	1.2173	0.073*
C9	0.1803 (3)	0.2046 (2)	1.0572 (2)	0.0495 (5)
Cl1	0.31643 (17)	0.29247 (10)	0.54306 (8)	0.1088 (4)
N1	0.3008 (3)	0.2749 (2)	0.94299 (19)	0.0535 (4)
N2	−0.0342 (3)	0.3294 (2)	0.88264 (18)	0.0498 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0686 (13)	0.0587 (12)	0.0545 (12)	−0.0238 (11)	−0.0075 (10)	0.0029 (10)
C2	0.0509 (11)	0.0472 (10)	0.0489 (11)	−0.0161 (8)	−0.0037 (8)	−0.0048 (8)
C3	0.0599 (13)	0.0680 (14)	0.0736 (15)	−0.0195 (11)	−0.0252 (11)	0.0030 (11)
C4	0.0505 (10)	0.0436 (10)	0.0495 (11)	−0.0146 (8)	−0.0031 (8)	−0.0077 (8)
C5	0.0550 (12)	0.0568 (12)	0.0676 (14)	−0.0235 (10)	0.0018 (10)	−0.0068 (10)
C6	0.0741 (15)	0.0634 (13)	0.0630 (14)	−0.0314 (12)	0.0101 (11)	−0.0041 (11)
C7	0.0840 (16)	0.0602 (13)	0.0512 (12)	−0.0235 (12)	−0.0033 (11)	0.0048 (10)
C8	0.0609 (13)	0.0639 (13)	0.0540 (12)	−0.0198 (10)	−0.0100 (10)	0.0006 (10)
C9	0.0513 (11)	0.0483 (10)	0.0474 (10)	−0.0173 (9)	−0.0040 (8)	−0.0042 (8)
Cl1	0.1675 (9)	0.0837 (5)	0.0523 (4)	−0.0326 (5)	0.0147 (4)	−0.0069 (3)
N1	0.0494 (9)	0.0588 (10)	0.0518 (10)	−0.0203 (8)	−0.0065 (7)	0.0006 (8)
N2	0.0465 (9)	0.0509 (9)	0.0520 (9)	−0.0170 (7)	−0.0082 (7)	−0.0028 (7)

Geometric parameters (Å, º) top

C1—C2	1.488 (3)	C4—N2	1.377 (3)
C1—Cl1	1.786 (2)	C4—C5	1.389 (3)
C1—H1A	0.9700	C4—C9	1.398 (3)
C1—H1B	0.9700	C5—C6	1.373 (3)
C2—N1	1.310 (3)	C5—H5	0.9300
C2—N2	1.363 (3)	C6—C7	1.397 (4)
C3—N2	1.453 (3)	C6—H6	0.9300
C3—H3A	0.9600	C7—C8	1.373 (3)
C3—H3B	0.9600	C7—H7	0.9300
C3—H3C	0.9600	C8—C9	1.390 (3)
C3—H3D	0.9600	C8—H8	0.9300
C3—H3E	0.9600	C9—N1	1.393 (3)
C3—H3F	0.9600

C2—C1—Cl1	110.86 (15)	H3B—C3—H3F	56.3
C2—C1—H1A	109.5	H3C—C3—H3F	141.1
Cl1—C1—H1A	109.5	H3D—C3—H3F	109.5
C2—C1—H1B	109.5	H3E—C3—H3F	109.5
Cl1—C1—H1B	109.5	N2—C4—C5	131.59 (19)
H1A—C1—H1B	108.1	N2—C4—C9	105.69 (17)
N1—C2—N2	114.14 (18)	C5—C4—C9	122.71 (19)
N1—C2—C1	123.36 (19)	C6—C5—C4	116.3 (2)
N2—C2—C1	122.49 (18)	C6—C5—H5	121.9
N2—C3—H3A	109.5	C4—C5—H5	121.9
N2—C3—H3B	109.5	C5—C6—C7	121.9 (2)
H3A—C3—H3B	109.5	C5—C6—H6	119.1
N2—C3—H3C	109.5	C7—C6—H6	119.1
H3A—C3—H3C	109.5	C8—C7—C6	121.5 (2)
H3B—C3—H3C	109.5	C8—C7—H7	119.3
N2—C3—H3D	109.5	C6—C7—H7	119.3
H3A—C3—H3D	141.1	C7—C8—C9	117.9 (2)
H3B—C3—H3D	56.3	C7—C8—H8	121.1
H3C—C3—H3D	56.3	C9—C8—H8	121.1
N2—C3—H3E	109.5	C8—C9—N1	130.36 (19)
H3A—C3—H3E	56.3	C8—C9—C4	119.77 (19)
H3B—C3—H3E	141.1	N1—C9—C4	109.87 (17)
H3C—C3—H3E	56.3	C2—N1—C9	104.17 (16)
H3D—C3—H3E	109.5	C2—N2—C4	106.13 (16)
N2—C3—H3F	109.5	C2—N2—C3	128.34 (18)
H3A—C3—H3F	56.3	C4—N2—C3	125.52 (17)

Experimental details

Crystal data
Chemical formula	C₉H₉ClN₂
M_r	180.63
Crystal system, space group	Triclinic, P1
Temperature (K)	296
a, b, c (Å)	6.607 (2), 8.168 (2), 8.925 (3)
α, β, γ (°)	84.566 (3), 79.682 (4), 68.134 (4)
V (Å³)	439.6 (2)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.38
Crystal size (mm)	0.37 × 0.29 × 0.18

Data collection
Diffractometer	Bruker SMART APEX CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2002)
T_min, T_max	0.874, 0.937
No. of measured, independent and observed [I > 2σ(I)] reflections	2191, 1523, 1361
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.597

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.122, 1.06
No. of reflections	1523
No. of parameters	109
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.32

Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEPIII (Burnett & Johnson, 1996) and ORTEP-3 for Windows (Farrugia, 1997).

Acknowledgements

This work was supported by 2009ZX09103–111 and the China Postdoctoral Science Foundation (No. 2009041446). We thank the Instrumental Analysis Center of Northwest University for the data collection at the CCD facility.

References

Allen, F. H. (2002). Acta Cryst. B58, 380–388. Web of Science CrossRef CAS IUCr Journals Google Scholar
Bruker (2002). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA. Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Horton, D. A., Bourne, G. T. & Sinythe, M. L. (2003). Chem. Rev. 103, 893–930. Web of Science CrossRef PubMed CAS Google Scholar
Laryea, D., Gullbo, J., Isakssoon, A., Larsson, R. & Nygren, P. (2010). Anti-Cancer Drugs, 21, 33–42. Web of Science CrossRef PubMed CAS Google Scholar
Matsui, T., Nakamura, Y., Ishikawa, H., Matsuura, A. & Kobayashi, F. (1994). Jpn J. Pharmacol. 64, 115–124. CrossRef CAS PubMed Web of Science Google Scholar
Migawa, M. T., Girardet, J. L., Walker, J. A., Koszalka, G. W., Chamberlain, S. D., Drach, J. C. & Townsend, L. B. (1998). J. Med. Chem. 41, 1242–1251. Web of Science CrossRef CAS PubMed Google Scholar
Porcari, A. R., Devivar, R. V., Kucera, L. S., Drach, J. C. & Townsend, L. B. (1998). J. Med. Chem. 41, 1252–1262. Web of Science CrossRef CAS PubMed Google Scholar
Rath, T., Morningstar, M. L., Boyer, P. L., Hughes, S. M., Buckheitjr, R. W. & Michejda, C. J. (1997). J. Med. Chem. 40, 4199–4207. PubMed Google Scholar
Refaat, H. M. (2010). Eur. J. Med. Chem. 45, 2949–2956. Web of Science CrossRef CAS PubMed Google Scholar
Ries, U. J., Priepke, H. W. M., Hauel, N. H., Haaksma, E. E. J., Stassen, J. M., Wienen, W. & Nar, H. (2003). Bioorg. Med. Chem. Lett. 13, 2297–2321. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spasov, A. A., Yozhitsa, I. N., Bugaeva, L. I. & Anisimova, V. A. (1999). Pharm. Chem. J. 33, 232–243. CrossRef CAS Google Scholar