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

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

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[Refaat, H. M. (2010). Eur. J. Med. Chem. 45, 2949-2956.]); Laryea et al. (2010[Laryea, D., Gullbo, J., Isakssoon, A., Larsson, R. & Nygren, P. (2010). Anti-Cancer Drugs, 21, 33-42.]); Horton et al. (2003[Horton, D. A., Bourne, G. T. & Sinythe, M. L. (2003). Chem. Rev. 103, 893-930.]); Ries et al. (2003[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.]); Spasov et al. (1999[Spasov, A. A., Yozhitsa, I. N., Bugaeva, L. I. & Anisimova, V. A. (1999). Pharm. Chem. J. 33, 232-243.]); Matsui et al. (1994[Matsui, T., Nakamura, Y., Ishikawa, H., Matsuura, A. & Kobayashi, F. (1994). Jpn J. Pharmacol. 64, 115-124.]); Porcari et al. (1998[Porcari, A. R., Devivar, R. V., Kucera, L. S., Drach, J. C. & Townsend, L. B. (1998). J. Med. Chem. 41, 1252-1262.]); Rath et al. (1997[Rath, T., Morningstar, M. L., Boyer, P. L., Hughes, S. M., Buckheitjr, R. W. & Michejda, C. J. (1997). J. Med. Chem. 40, 4199-4207.]); Migawa et al. (1998[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.]). For a description of the Cambridge Structural Database, see: Allen (2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]).

[Scheme 1]

Experimental

Crystal data
  • C9H9ClN2

  • Mr = 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[Bruker (2002). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.874, Tmax = 0.937

  • 2191 measured reflections

  • 1523 independent reflections

  • 1361 reflections with I > 2σ(I)

  • Rint = 0.018

Refinement
  • R[F2 > 2σ(F2)] = 0.042

  • wR(F2) = 0.122

  • S = 1.06

  • 1523 reflections

  • 109 parameters

  • H-atom parameters constrained

  • Δρmax = 0.20 e Å−3

  • Δρmin = −0.32 e Å−3

Data collection: SMART (Bruker, 2002[Bruker (2002). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2002[Bruker (2002). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; 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: ORTEPIII (Burnett & Johnson, 1996[Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.]) and ORTEP-3 for Windows (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]); software used to prepare material for publication: SHELXL97.

Supporting information


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.

Refinement top

All H atoms were fixed geometrically and treated as riding with C—H = 0.96 Å (methyl), 0.97 Å (methylene) and 0.93 Å (aromatic) with Uiso(H) = 1.2Ueq(C, aromatic or methylene) and Uiso(H) = 1.5Ueq(C, methyl).

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
[Figure 1] 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
C9H9ClN2Z = 2
Mr = 180.63F(000) = 188
Triclinic, P1Dx = 1.365 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 6.607 (2) ÅCell parameters from 2191 reflections
b = 8.168 (2) Åθ = 2.3–25.1°
c = 8.925 (3) ŵ = 0.38 mm1
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 tube1361 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.018
ϕ and ω scansθmax = 25.1°, θmin = 2.3°
Absorption correction: multi-scan
(SADABS; Bruker, 2002)
h = 75
Tmin = 0.874, Tmax = 0.937k = 99
2191 measured reflectionsl = 1010
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)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.122H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0552P)2 + 0.1656P]
where P = (Fo2 + 2Fc2)/3
1523 reflections(Δ/σ)max < 0.001
109 parametersΔρmax = 0.20 e Å3
0 restraintsΔρmin = 0.32 e Å3
Crystal data top
C9H9ClN2γ = 68.134 (4)°
Mr = 180.63V = 439.6 (2) Å3
Triclinic, P1Z = 2
a = 6.607 (2) ÅMo Kα radiation
b = 8.168 (2) ŵ = 0.38 mm1
c = 8.925 (3) ÅT = 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)
Tmin = 0.874, Tmax = 0.937Rint = 0.018
2191 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0420 restraints
wR(F2) = 0.122H-atom parameters constrained
S = 1.06Δρmax = 0.20 e Å3
1523 reflectionsΔρmin = 0.32 e Å3
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
xyzUiso*/UeqOcc. (<1)
C10.2259 (4)0.4372 (3)0.6995 (2)0.0610 (6)
H1A0.34240.47810.71090.073*
H1B0.09850.53930.67900.073*
C20.1665 (3)0.3458 (2)0.8432 (2)0.0498 (5)
C30.2214 (4)0.3954 (3)0.8004 (3)0.0666 (6)
H3A0.34050.36380.85630.100*0.50
H3B0.17880.34440.70170.100*0.50
H3C0.26830.52150.78880.100*0.50
H3D0.18460.45600.70820.100*0.50
H3E0.34630.47540.86280.100*0.50
H3F0.25680.29830.77570.100*0.50
C40.0294 (3)0.2393 (2)1.0212 (2)0.0488 (5)
C50.1859 (4)0.1843 (3)1.1144 (3)0.0600 (6)
H50.32420.20691.08850.072*
C60.1250 (4)0.0947 (3)1.2471 (3)0.0675 (6)
H60.22580.05741.31370.081*
C70.0842 (4)0.0581 (3)1.2848 (3)0.0673 (6)
H70.11980.00411.37510.081*
C80.2384 (4)0.1119 (3)1.1915 (2)0.0605 (6)
H80.37730.08711.21730.073*
C90.1803 (3)0.2046 (2)1.0572 (2)0.0495 (5)
Cl10.31643 (17)0.29247 (10)0.54306 (8)0.1088 (4)
N10.3008 (3)0.2749 (2)0.94299 (19)0.0535 (4)
N20.0342 (3)0.3294 (2)0.88264 (18)0.0498 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0686 (13)0.0587 (12)0.0545 (12)0.0238 (11)0.0075 (10)0.0029 (10)
C20.0509 (11)0.0472 (10)0.0489 (11)0.0161 (8)0.0037 (8)0.0048 (8)
C30.0599 (13)0.0680 (14)0.0736 (15)0.0195 (11)0.0252 (11)0.0030 (11)
C40.0505 (10)0.0436 (10)0.0495 (11)0.0146 (8)0.0031 (8)0.0077 (8)
C50.0550 (12)0.0568 (12)0.0676 (14)0.0235 (10)0.0018 (10)0.0068 (10)
C60.0741 (15)0.0634 (13)0.0630 (14)0.0314 (12)0.0101 (11)0.0041 (11)
C70.0840 (16)0.0602 (13)0.0512 (12)0.0235 (12)0.0033 (11)0.0048 (10)
C80.0609 (13)0.0639 (13)0.0540 (12)0.0198 (10)0.0100 (10)0.0006 (10)
C90.0513 (11)0.0483 (10)0.0474 (10)0.0173 (9)0.0040 (8)0.0042 (8)
Cl10.1675 (9)0.0837 (5)0.0523 (4)0.0326 (5)0.0147 (4)0.0069 (3)
N10.0494 (9)0.0588 (10)0.0518 (10)0.0203 (8)0.0065 (7)0.0006 (8)
N20.0465 (9)0.0509 (9)0.0520 (9)0.0170 (7)0.0082 (7)0.0028 (7)
Geometric parameters (Å, º) top
C1—C21.488 (3)C4—N21.377 (3)
C1—Cl11.786 (2)C4—C51.389 (3)
C1—H1A0.9700C4—C91.398 (3)
C1—H1B0.9700C5—C61.373 (3)
C2—N11.310 (3)C5—H50.9300
C2—N21.363 (3)C6—C71.397 (4)
C3—N21.453 (3)C6—H60.9300
C3—H3A0.9600C7—C81.373 (3)
C3—H3B0.9600C7—H70.9300
C3—H3C0.9600C8—C91.390 (3)
C3—H3D0.9600C8—H80.9300
C3—H3E0.9600C9—N11.393 (3)
C3—H3F0.9600
C2—C1—Cl1110.86 (15)H3B—C3—H3F56.3
C2—C1—H1A109.5H3C—C3—H3F141.1
Cl1—C1—H1A109.5H3D—C3—H3F109.5
C2—C1—H1B109.5H3E—C3—H3F109.5
Cl1—C1—H1B109.5N2—C4—C5131.59 (19)
H1A—C1—H1B108.1N2—C4—C9105.69 (17)
N1—C2—N2114.14 (18)C5—C4—C9122.71 (19)
N1—C2—C1123.36 (19)C6—C5—C4116.3 (2)
N2—C2—C1122.49 (18)C6—C5—H5121.9
N2—C3—H3A109.5C4—C5—H5121.9
N2—C3—H3B109.5C5—C6—C7121.9 (2)
H3A—C3—H3B109.5C5—C6—H6119.1
N2—C3—H3C109.5C7—C6—H6119.1
H3A—C3—H3C109.5C8—C7—C6121.5 (2)
H3B—C3—H3C109.5C8—C7—H7119.3
N2—C3—H3D109.5C6—C7—H7119.3
H3A—C3—H3D141.1C7—C8—C9117.9 (2)
H3B—C3—H3D56.3C7—C8—H8121.1
H3C—C3—H3D56.3C9—C8—H8121.1
N2—C3—H3E109.5C8—C9—N1130.36 (19)
H3A—C3—H3E56.3C8—C9—C4119.77 (19)
H3B—C3—H3E141.1N1—C9—C4109.87 (17)
H3C—C3—H3E56.3C2—N1—C9104.17 (16)
H3D—C3—H3E109.5C2—N2—C4106.13 (16)
N2—C3—H3F109.5C2—N2—C3128.34 (18)
H3A—C3—H3F56.3C4—N2—C3125.52 (17)

Experimental details

Crystal data
Chemical formulaC9H9ClN2
Mr180.63
Crystal system, space groupTriclinic, 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)
V3)439.6 (2)
Z2
Radiation typeMo Kα
µ (mm1)0.38
Crystal size (mm)0.37 × 0.29 × 0.18
Data collection
DiffractometerBruker SMART APEX CCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2002)
Tmin, Tmax0.874, 0.937
No. of measured, independent and
observed [I > 2σ(I)] reflections
2191, 1523, 1361
Rint0.018
(sin θ/λ)max1)0.597
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.042, 0.122, 1.06
No. of reflections1523
No. of parameters109
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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

First citationAllen, F. H. (2002). Acta Cryst. B58, 380–388.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationBruker (2002). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationBurnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.  Google Scholar
First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals Google Scholar
First citationHorton, D. A., Bourne, G. T. & Sinythe, M. L. (2003). Chem. Rev. 103, 893–930.  Web of Science CrossRef PubMed CAS Google Scholar
First citationLaryea, D., Gullbo, J., Isakssoon, A., Larsson, R. & Nygren, P. (2010). Anti-Cancer Drugs, 21, 33–42.  Web of Science CrossRef PubMed CAS Google Scholar
First citationMatsui, T., Nakamura, Y., Ishikawa, H., Matsuura, A. & Kobayashi, F. (1994). Jpn J. Pharmacol. 64, 115–124.  CrossRef CAS PubMed Web of Science Google Scholar
First citationMigawa, 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
First citationPorcari, 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
First citationRath, 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
First citationRefaat, H. M. (2010). Eur. J. Med. Chem. 45, 2949–2956.  Web of Science CrossRef CAS PubMed Google Scholar
First citationRies, 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
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSpasov, A. A., Yozhitsa, I. N., Bugaeva, L. I. & Anisimova, V. A. (1999). Pharm. Chem. J. 33, 232–243.  CrossRef CAS Google Scholar

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