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Acta Crystallogr Sect E Struct Rep Online. 2008 April 1; 64(Pt 4): o671–o672.
Published online 2008 March 5. doi:  10.1107/S1600536808005886
PMCID: PMC2961028

1-Methyl-6-nitro-1H-benzimidazole

Abstract

The title compound, C8H7N3O2, a potential anti­tumour drug and an anti­oxidant agent, was studied in order to give more insight into structure–function relationships. The 1-methyl­benzimidazole unit of the mol­ecule was found to be exactly planar and the nitro group is inclined at an angle of 10.4 (2)° to the plane of the heterocycle. The bond lengths in the present derivative were analyzed in details and compared with those of the parent unsubstituted analogues in the Cambridge Structural Database. The results have shown that the additional nitro group is not involved in conjugation with the adjacent π-system and hence has no effect on the charge distribution of the heterocyclic ring.

Related literature

For related literature on related crystal structures, see for example: Türktekin et al., (2004 [triangle]) as retrieved from the Cambridge Structural Database (Version of 2007; Allen, 2002 [triangle]). For the synthesis, see: Ellis & Jones (1974 [triangle]). For the length of the pure Csp 2—Nsp 2 single bond, see: Adler et al. (1976 [triangle]). For related literature on biological aspects of the benzimidazole derivatives in general, see: Alpan et al. (2007 [triangle]); Kettmann et al. (2004 [triangle]); Le et al. (2004 [triangle]); Nguyen et al. (2004 [triangle]); Statkova-Abeghe et al. (2005 [triangle]). Anti­oxidant properties of the compound are discussed by Hanus et al. (2004 [triangle]); Katuščák (2003 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-0o671-scheme1.jpg

Experimental

Crystal data

  • C8H7N3O2
  • M r = 177.17
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o671-efi1.jpg
  • a = 12.852 (3) Å
  • b = 7.043 (2) Å
  • c = 17.690 (4) Å
  • V = 1601.2 (7) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.11 mm−1
  • T = 296 (2) K
  • 0.30 × 0.20 × 0.15 mm

Data collection

  • Siemens P4 diffractometer
  • Absorption correction: none
  • 3027 measured reflections
  • 2325 independent reflections
  • 1493 reflections with I > 2σ(I)
  • R int = 0.035
  • 3 standard reflections every 97 reflections intensity decay: none

Refinement

  • R[F 2 > 2σ(F 2)] = 0.045
  • wR(F 2) = 0.130
  • S = 0.96
  • 2325 reflections
  • 119 parameters
  • H-atom parameters constrained
  • Δρmax = 0.18 e Å−3
  • Δρmin = −0.15 e Å−3

Data collection: XSCANS (Siemens, 1991 [triangle]); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2003 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Selected bond lengths (Å)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808005886/nc2091sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808005886/nc2091Isup2.hkl

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

Acknowledgments

This work was supported by the Grant Agency of the Slovak Republic (project Nos. 1/4298/07 and 1/0225/08) as well as by the Science and Technology Assistance Agency (APVV-20–007304). The authors also thank the Ministry of Education of the Slovak Republic (contract No. 2003SP200280301).

supplementary crystallographic information

Comment

Benzimidazole derivatives are known to possess a variety of biological properties (Le et al., 2004), the anti-cancer activity being one of the most important (Nguyen et al., 2004). Recently, it has been reported that the cytotoxic activity of 1H-benzimidazoles is related to inhibition of the DNA-topoisomerase binary complex and is potentiated by introduction to the 6-position of a small substituent containing an oxygen atom able to accept a hydrogen bond (e.g. nitro, acetyl, amide) (Alpan et al., 2007; Statkova-Abeghe et al., 2005). It was, however, unclear whether the influence of the substituents reflects their effect on the charge distribution of the heterocycle or results from interaction of the substituents with additional DNA or enzyme functionalities. Consequently, we prepared a series of 6-substituted 1-methylbenzimidazoles and determined and compared their molecular and electronic structures by using theoretical and experimental techniques. In this communication we report the crystal structure of the 6-nitro derivative, (I). Another point of interest in (I) stems from its use in paper processing as an antioxidant agent (Katuščák, 2003; Hanus et al., 2004), a property which is also dependent on the molecular and electronic structures of the compound.

As expected, the 1-methylbenzimidazole substructure is planar to within experimental error and the nitro group is rotated by 10.4 (2)° from the plane of the heterocycle (Fig.1).

As mentioned above, the main purpose of this work was to compare precise molecular dimensions in the present derivative, (I), with those of the unsubstituted 1-methylbenzimidazole. As the latter compound has no entry in the Cambridge Structural Database (CSD, Version of 2007; Allen & Kennard, 1983), the CSD was searched for compounds possessing the benzimidazole nucleus and just 1-substituent with methylene group in the α-position; 42 such compounds [hereafter (II)] were found. The comparison have shown that the corresponding bond lengths in the benzimidazole heterocycle in (I) and in the molecules of (II) are equal within the limits of experimental error. This, along with the single-bond character of C6—N4 (Adler et al., 1976) indicates that the nitro group is deconjugated with the benzimidazole ring. This implies that the large difference in cytotoxic activities between (I) and (II) lies in the interaction of the 6-substituent with additional DNA intercalation component or enzyme amino acid residues which surrounds the intercalation site (Kettmann et al., 2004). These results will serve as a basis for subsequent molecular-modelling studies of the DNA-enzyme-ligand interactions.

Experimental

The synthesis of the title compound, (I), was described earlier (Ellis & Jones, 1974). In short, a solution of formaldehyde (4 g, 0.133 mol) in absolute ethanol (40 ml) was heated under reflux for 30 min with commercially available 4-nitro-1,2-phenylenediamine (7.1 g, 0.046 mol) and concentrated hydrochloric acid (3 ml). On basification with ammonia, (I) was obtained as yellow crystals (25% yield; m.p. 454–456 K).

Refinement

H atoms were visible in difference maps but were placed in calculated positions and were refined isotropic (Uiso of the H atoms were set to 1.2 (1.5 for the methyl H atoms) times Ueq of the parent atom) using a riding model with C—H = 0.93 Å (CHarom) and 0.96 Å (CH3).

Figures

Fig. 1.
Displacement ellipsoid plot of the title molecule with the labelling scheme for the non-H atoms, which are drawn as 35% probability ellipsoids.

Crystal data

C8H7N3O2Dx = 1.470 Mg m3
Mr = 177.17Melting point: 455 K
Orthorhombic, PbcaMo Kα radiation λ = 0.71073 Å
Hall symbol: -P 2ac 2abCell parameters from 20 reflections
a = 12.852 (3) Åθ = 7–19º
b = 7.043 (2) ŵ = 0.11 mm1
c = 17.690 (4) ÅT = 296 (2) K
V = 1601.2 (7) Å3Prism, yellow
Z = 80.30 × 0.20 × 0.15 mm
F000 = 736

Data collection

Siemens P4 diffractometerRint = 0.035
Radiation source: fine-focus sealed tubeθmax = 30.0º
Monochromator: graphiteθmin = 2.3º
T = 296(2) Kh = −1→18
ω/2θ scansk = −1→9
Absorption correction: nonel = −24→1
3027 measured reflections3 standard reflections
2325 independent reflections every 97 reflections
1493 reflections with I > 2σ(I) intensity decay: none

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.045H-atom parameters constrained
wR(F2) = 0.130  w = 1/[σ2(Fo2) + (0.0722P)2] where P = (Fo2 + 2Fc2)/3
S = 0.96(Δ/σ)max = 0.002
2325 reflectionsΔρmax = 0.18 e Å3
119 parametersΔρmin = −0.15 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

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.
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)

xyzUiso*/Ueq
N10.42194 (9)0.26257 (16)0.47003 (6)0.0416 (3)
C20.52515 (10)0.2941 (2)0.45973 (9)0.0497 (4)
H20.55250.33600.41400.060*
N30.58338 (9)0.26080 (19)0.51910 (7)0.0532 (3)
C40.53023 (11)0.1419 (2)0.64798 (8)0.0553 (4)
H40.59680.14190.66860.066*
C50.44659 (12)0.0845 (2)0.68983 (8)0.0544 (4)
H50.45610.04320.73930.065*
C60.34599 (10)0.08772 (19)0.65813 (7)0.0425 (3)
C70.32568 (9)0.14664 (19)0.58497 (7)0.0390 (3)
H70.25870.14960.56500.047*
C80.41167 (10)0.20061 (17)0.54376 (7)0.0374 (3)
C90.51357 (10)0.20067 (19)0.57335 (8)0.0444 (3)
C100.33948 (11)0.2912 (3)0.41540 (9)0.0555 (4)
H10A0.34280.41850.39620.083*
H10B0.27330.27110.43930.083*
H10C0.34760.20290.37450.083*
N40.25815 (11)0.03037 (18)0.70486 (7)0.0499 (3)
O10.16986 (9)0.0586 (2)0.68211 (6)0.0653 (3)
O20.27589 (11)−0.0462 (2)0.76606 (6)0.0721 (4)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0348 (5)0.0474 (6)0.0425 (6)−0.0030 (4)−0.0002 (4)0.0008 (5)
C20.0376 (7)0.0532 (8)0.0583 (8)−0.0041 (6)0.0085 (6)−0.0036 (7)
N30.0334 (6)0.0599 (8)0.0663 (8)−0.0019 (5)0.0008 (5)−0.0071 (6)
C40.0428 (7)0.0662 (9)0.0570 (8)0.0084 (7)−0.0178 (6)−0.0072 (8)
C50.0592 (9)0.0607 (9)0.0434 (7)0.0103 (7)−0.0138 (7)−0.0029 (7)
C60.0460 (7)0.0436 (7)0.0379 (6)0.0027 (6)−0.0017 (5)−0.0048 (5)
C70.0350 (6)0.0417 (6)0.0404 (6)0.0007 (5)−0.0039 (5)−0.0044 (6)
C80.0349 (6)0.0376 (6)0.0398 (6)0.0011 (5)−0.0036 (5)−0.0046 (5)
C90.0348 (6)0.0450 (7)0.0535 (8)0.0029 (5)−0.0055 (6)−0.0089 (6)
C100.0477 (8)0.0748 (10)0.0441 (7)−0.0036 (7)−0.0071 (6)0.0084 (7)
N40.0605 (8)0.0515 (7)0.0377 (6)−0.0001 (6)0.0029 (5)−0.0052 (5)
O10.0503 (6)0.0928 (9)0.0527 (6)−0.0051 (6)0.0055 (5)0.0053 (6)
O20.0891 (10)0.0851 (9)0.0420 (6)0.0051 (7)0.0043 (6)0.0149 (6)

Geometric parameters (Å, °)

N1—C21.3571 (17)C6—C71.3840 (19)
N1—C81.3817 (17)C6—N41.4563 (18)
N1—C101.4483 (18)C7—C81.3775 (18)
C2—N31.3107 (19)C7—H70.9300
C2—H20.9300C8—C91.4104 (17)
N3—C91.3803 (18)C10—H10A0.9600
C4—C51.366 (2)C10—H10B0.9600
C4—C91.4001 (19)C10—H10C0.9600
C4—H40.9300N4—O11.2202 (16)
C5—C61.4095 (19)N4—O21.2308 (16)
C5—H50.9300
C2—N1—C8105.76 (11)C8—C7—H7122.4
C2—N1—C10127.08 (12)C6—C7—H7122.4
C8—N1—C10127.15 (11)C7—C8—N1131.56 (12)
N3—C2—N1114.93 (13)C7—C8—C9123.28 (12)
N3—C2—H2122.5N1—C8—C9105.17 (11)
N1—C2—H2122.5N3—C9—C4130.31 (13)
C2—N3—C9103.93 (12)N3—C9—C8110.22 (12)
C5—C4—C9118.57 (13)C4—C9—C8119.46 (13)
C5—C4—H4120.7N1—C10—H10A109.5
C9—C4—H4120.7N1—C10—H10B109.5
C4—C5—C6120.08 (13)H10A—C10—H10B109.5
C4—C5—H5120.0N1—C10—H10C109.5
C6—C5—H5120.0H10A—C10—H10C109.5
C7—C6—C5123.36 (13)H10B—C10—H10C109.5
C7—C6—N4117.89 (12)O1—N4—O2122.26 (14)
C5—C6—N4118.74 (12)O1—N4—C6119.23 (12)
C8—C7—C6115.24 (11)O2—N4—C6118.50 (13)
C8—N1—C2—N3−0.55 (16)C10—N1—C8—C9−178.72 (13)
C10—N1—C2—N3178.49 (14)C2—N3—C9—C4178.82 (15)
N1—C2—N3—C90.52 (16)C2—N3—C9—C8−0.29 (15)
C9—C4—C5—C6−0.9 (2)C5—C4—C9—N3−178.51 (14)
C4—C5—C6—C70.2 (2)C5—C4—C9—C80.5 (2)
C4—C5—C6—N4−178.40 (14)C7—C8—C9—N3179.82 (12)
C5—C6—C7—C80.9 (2)N1—C8—C9—N3−0.02 (15)
N4—C6—C7—C8179.47 (11)C7—C8—C9—C40.6 (2)
C6—C7—C8—N1178.54 (13)N1—C8—C9—C4−179.25 (12)
C6—C7—C8—C9−1.26 (19)C7—C6—N4—O1−9.28 (19)
C2—N1—C8—C7−179.50 (14)C5—C6—N4—O1169.38 (13)
C10—N1—C8—C71.5 (2)C7—C6—N4—O2170.32 (13)
C2—N1—C8—C90.32 (14)C5—C6—N4—O2−11.02 (19)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: NC2091).

References

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