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Acta Crystallogr Sect E Struct Rep Online. 2009 February 1; 65(Pt 2): o226.
Published online 2009 January 8. doi:  10.1107/S1600536808043420
PMCID: PMC2968158

4-Methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid

Abstract

In the title compound, C12H14N2O2, the benzene ring and imidazole ring are almost coplanar, making a dihedral angle of 2.47 (14)°. Inter­molecular O—H(...)N, N—H(...)O and C—H(...)O hydrogen bonds stabilize the crystal structure.

Related literature

For the use of the title compound as an inter­mediate in the preparation of telmisartan, see: Ries et al. (1993 [triangle]). For the biological activity of telmisartan, see: Engeli et al. (2000 [triangle]); Goossens et al. (2003 [triangle]). For reference structural data, see: Allen et al. (1987 [triangle]). For related literature, see: Kintscher et al. (2004 [triangle]).

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Object name is e-65-0o226-scheme1.jpg

Experimental

Crystal data

  • C12H14N2O2
  • M r = 218.25
  • Tetragonal, An external file that holds a picture, illustration, etc.
Object name is e-65-0o226-efi1.jpg
  • a = 12.0548 (17) Å
  • c = 31.899 (6) Å
  • V = 4635.5 (13) Å3
  • Z = 16
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 293 (2) K
  • 0.30 × 0.30 × 0.10 mm

Data collection

  • Enraf–Nonuis CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.975, T max = 0.991
  • 4426 measured reflections
  • 2105 independent reflections
  • 1304 reflections with I > 2σ(I)
  • R int = 0.042
  • 3 standard reflections every 200 reflections intensity decay: none

Refinement

  • R[F 2 > 2σ(F 2)] = 0.072
  • wR(F 2) = 0.195
  • S = 1.00
  • 2105 reflections
  • 133 parameters
  • 2 restraints
  • H-atom parameters constrained
  • Δρmax = 0.62 e Å−3
  • Δρmin = −0.39 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius,1989 [triangle]); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo,1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808043420/sj2567sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808043420/sj2567Isup2.hkl

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

Acknowledgments

The authors thank the Center of Testing and Analysis, Nanjing University, for support.

supplementary crystallographic information

Comment

The title compound (I), Fig. 1, 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid is an important intermediate in the preparation of the angiotensin II receptor blocker telmisartan (Ries et al.,1993). Telmisartan is used as a therapeutic tool for metabolic problems, including visceral obesity (Engeli et al., 2000; Goossens et al., 2003). Bond lengths in the compound are within normal ranges (Allen et al., 1987) and the benzene and imidazole rings are coplanar with a dihedral angle of 2.47 (14)° between them.

In the crystal structure, intermolecular O—H···N, N—H···O and C—H···O hydrogen bonds, Table 1, link the molecules, Fig. 2, and stabilise the crystal packing.

Experimental

The title compound was prepared from methyl 4-(butyrylamino)-5-methyl -3-aminobenzoate (13 g 52 mmol) in xylene (60 mL) and hydrochloric acid (130 mL). The mixture was refluxed for 3 h at 423 K, concentrated under reduced pressure then 80mL of methanol and 110 mL 15% sodium hydroxide were added. This solution was further , refluxed for 5 h at 383 K. The pH was adjusted to below 7 and the product filtered. Recrystallization of product from a mixture of ethanol/water (5:1) afforded the white powder. Crystals were obtained by dissolving the product (1.0 g) in acetone (10 ml) and evaporating slowly at room temperature for about 30 d.

Refinement

H All atoms were positioned geometrically, with N—H = 0.86 Å (for NH) and C—H = 0.93, 0.97 and 0.96 Å for aromatic, methine and methyl H, and constrained to ride on their parent atoms, with Uiso(H) = xUeq(C,N), where x = 1.5 for methyl H, and x = 1.2 for all other H atoms.

Figures

Fig. 1.
The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
Fig. 2.
Crystal packing of the title compound with hydrogen bonds drawn as dashed lines.

Crystal data

C12H14N2O2Dx = 1.251 Mg m3
Mr = 218.25Mo Kα radiation, λ = 0.71073 Å
Tetragonal, I41/aCell parameters from 25 reflections
Hall symbol: -I 4adθ = 10–13°
a = 12.0548 (17) ŵ = 0.09 mm1
c = 31.899 (6) ÅT = 293 K
V = 4635.5 (13) Å3Block, colorless
Z = 160.30 × 0.30 × 0.10 mm
F(000) = 1856

Data collection

Enraf–Nonuis CAD-4 diffractometer1304 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.042
graphiteθmax = 25.2°, θmin = 1.8°
ω/2θ scansh = −9→10
Absorption correction: ψ scan (North et al., 1968)k = 0→14
Tmin = 0.975, Tmax = 0.991l = 0→38
4426 measured reflections3 standard reflections every 200 reflections
2105 independent reflections 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)] = 0.072H-atom parameters constrained
wR(F2) = 0.195w = 1/[σ2(Fo2) + (0.1P)2 + 5P] where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
2105 reflectionsΔρmax = 0.62 e Å3
133 parametersΔρmin = −0.39 e Å3
2 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008)
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.039 (3)

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
O10.7815 (2)0.4947 (2)0.07388 (7)0.0591 (8)
O20.7256 (2)0.32125 (18)0.07006 (6)0.0471 (7)
H2C0.70770.33410.09440.071*
N10.8807 (2)0.3584 (2)−0.11544 (7)0.0376 (7)
N20.8170 (2)0.2123 (2)−0.08282 (7)0.0420 (7)
H2D0.79400.1458−0.07850.050*
C10.6545 (5)0.2486 (5)−0.18175 (17)0.104
H1B0.58910.2171−0.19410.155*
H1C0.68430.3042−0.20010.155*
H1D0.63580.2818−0.15530.155*
C20.7407 (4)0.1577 (5)−0.17491 (18)0.100
H2A0.70970.1043−0.15540.120*
H2B0.75130.1195−0.20140.120*
C30.8501 (3)0.1904 (3)−0.15925 (10)0.0561 (10)
H3A0.88600.2355−0.18050.067*
H3B0.89450.1239−0.15570.067*
C40.8509 (3)0.2525 (3)−0.11926 (9)0.0402 (8)
C50.8656 (2)0.3874 (3)−0.07355 (9)0.0324 (7)
C60.8820 (2)0.4885 (2)−0.05283 (9)0.0341 (7)
C70.8539 (2)0.4896 (3)−0.01107 (9)0.0351 (7)
H7A0.86530.55430.00420.042*
C80.8085 (2)0.3966 (2)0.00960 (9)0.0315 (7)
C90.7938 (3)0.2969 (2)−0.01128 (9)0.0353 (8)
H9A0.76450.23500.00210.042*
C100.8246 (3)0.2941 (2)−0.05289 (9)0.0325 (7)
C110.9269 (3)0.5876 (3)−0.07572 (11)0.0523 (10)
H11A0.94100.5681−0.10440.078*
H11B0.99470.6112−0.06270.078*
H11C0.87370.6467−0.07470.078*
C120.7704 (3)0.4069 (2)0.05433 (9)0.0352 (7)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.097 (2)0.0411 (14)0.0391 (14)−0.0157 (14)0.0171 (13)−0.0130 (11)
O20.0713 (17)0.0394 (13)0.0306 (12)−0.0073 (12)0.0238 (11)−0.0056 (10)
N10.0401 (16)0.0475 (17)0.0250 (13)0.0030 (13)0.0022 (11)0.0055 (12)
N20.0599 (19)0.0366 (15)0.0295 (13)−0.0022 (13)0.0098 (13)0.0006 (12)
C10.1040.1040.1040.0000.0000.000
C20.1000.1000.1000.0000.0000.000
C30.062 (2)0.079 (3)0.0275 (18)0.006 (2)0.0032 (16)−0.0106 (17)
C40.0392 (19)0.056 (2)0.0250 (16)0.0079 (16)0.0066 (14)0.0000 (15)
C50.0309 (16)0.0392 (18)0.0271 (15)0.0063 (13)0.0052 (13)0.0077 (13)
C60.0356 (17)0.0303 (17)0.0365 (17)−0.0015 (13)0.0005 (14)0.0093 (13)
C70.0379 (18)0.0330 (17)0.0345 (16)−0.0008 (13)0.0032 (13)−0.0027 (13)
C80.0410 (18)0.0273 (16)0.0261 (15)0.0038 (13)0.0033 (13)0.0040 (12)
C90.0472 (19)0.0318 (17)0.0269 (16)−0.0020 (14)0.0091 (13)0.0032 (13)
C100.0454 (19)0.0293 (16)0.0229 (14)0.0015 (13)0.0046 (13)0.0015 (12)
C110.064 (2)0.041 (2)0.052 (2)−0.0089 (17)0.0104 (18)0.0146 (17)
C120.0430 (19)0.0321 (17)0.0305 (16)0.0009 (14)0.0040 (14)−0.0042 (14)

Geometric parameters (Å, °)

O1—C121.237 (4)C3—H3A0.9700
O2—C121.268 (3)C3—H3B0.9700
O2—H2C0.8200C5—C101.394 (4)
N1—C41.332 (4)C5—C61.400 (4)
N1—C51.393 (4)C6—C71.374 (4)
N2—C41.324 (4)C6—C111.501 (4)
N2—C101.376 (4)C7—C81.411 (4)
N2—H2D0.8600C7—H7A0.9300
C1—C21.526 (6)C8—C91.385 (4)
C1—H1B0.9600C8—C121.504 (4)
C1—H1C0.9600C9—C101.379 (4)
C1—H1D0.9600C9—H9A0.9300
C2—C31.465 (6)C11—H11A0.9600
C2—H2A0.9700C11—H11B0.9600
C2—H2B0.9700C11—H11C0.9600
C3—C41.479 (4)
C12—O2—H2C109.5N1—C5—C6130.7 (3)
C4—N1—C5107.0 (2)C10—C5—C6121.9 (3)
C4—N2—C10109.1 (3)C7—C6—C5115.5 (3)
C4—N2—H2D125.5C7—C6—C11123.5 (3)
C10—N2—H2D125.5C5—C6—C11120.9 (3)
C2—C1—H1B109.5C6—C7—C8122.7 (3)
C2—C1—H1C109.5C6—C7—H7A118.6
H1B—C1—H1C109.5C8—C7—H7A118.6
C2—C1—H1D109.5C9—C8—C7120.9 (3)
H1B—C1—H1D109.5C9—C8—C12119.2 (3)
H1C—C1—H1D109.5C7—C8—C12119.8 (3)
C3—C2—C1118.0 (5)C10—C9—C8116.7 (3)
C3—C2—H2A107.8C10—C9—H9A121.6
C1—C2—H2A107.8C8—C9—H9A121.6
C3—C2—H2B107.8N2—C10—C9131.9 (3)
C1—C2—H2B107.8N2—C10—C5105.9 (2)
H2A—C2—H2B107.2C9—C10—C5122.1 (3)
C2—C3—C4115.8 (4)C6—C11—H11A109.5
C2—C3—H3A108.3C6—C11—H11B109.5
C4—C3—H3A108.3H11A—C11—H11B109.5
C2—C3—H3B108.3C6—C11—H11C109.5
C4—C3—H3B108.3H11A—C11—H11C109.5
H3A—C3—H3B107.4H11B—C11—H11C109.5
N2—C4—N1110.7 (3)O1—C12—O2122.9 (3)
N2—C4—C3124.8 (3)O1—C12—C8121.1 (3)
N1—C4—C3124.5 (3)O2—C12—C8116.0 (3)
N1—C5—C10107.3 (3)
C1—C2—C3—C456.3 (6)C6—C7—C8—C12−174.6 (3)
C10—N2—C4—N1−0.2 (4)C7—C8—C9—C10−0.6 (5)
C10—N2—C4—C3−177.3 (3)C12—C8—C9—C10176.5 (3)
C5—N1—C4—N20.5 (4)C4—N2—C10—C9175.5 (3)
C5—N1—C4—C3177.5 (3)C4—N2—C10—C5−0.1 (4)
C2—C3—C4—N263.9 (5)C8—C9—C10—N2−176.8 (3)
C2—C3—C4—N1−112.7 (4)C8—C9—C10—C5−1.8 (5)
C4—N1—C5—C10−0.5 (3)N1—C5—C10—N20.4 (3)
C4—N1—C5—C6−178.6 (3)C6—C5—C10—N2178.6 (3)
N1—C5—C6—C7177.2 (3)N1—C5—C10—C9−175.7 (3)
C10—C5—C6—C7−0.6 (4)C6—C5—C10—C92.5 (5)
N1—C5—C6—C11−2.5 (5)C9—C8—C12—O1−179.5 (3)
C10—C5—C6—C11179.7 (3)C7—C8—C12—O1−2.4 (5)
C5—C6—C7—C8−1.8 (4)C9—C8—C12—O2−0.4 (4)
C11—C6—C7—C8177.9 (3)C7—C8—C12—O2176.7 (3)
C6—C7—C8—C92.4 (5)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C3—H3B···O2i0.972.563.399 (4)144
C11—H11A···O2ii0.962.663.587 (4)163
O2—H2C···N1iii0.821.802.562 (3)153
N2—H2D···O1iv0.861.832.673 (3)165

Symmetry codes: (i) y+3/4, −x+3/4, z−1/4; (ii) −y+5/4, x−1/4, z−1/4; (iii) y+1/4, −x+5/4, z+1/4; (iv) x, y−1/2, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ2567).

References

  • Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
  • Engeli, S., Negrel, R. & Sharma, A. M. (2000). Hypertension, 35, 1270–1277. [PubMed]
  • Enraf–Nonius (1989). CAD-4 Software Enraf–Nonius, Delft, The Netherlands.
  • Goossens, G. H., Blaak, E. E. & van Baak, M. A. (2003). Obes. Rev.4, 43–55. [PubMed]
  • Harms, K. & Wocadlo, S. (1995). XCAD4 University of Marburg, Germany.
  • Kintscher, U., Lyon, C. J. & Law, R. E. (2004). Front. Biosci 9, 359–369. [PubMed]
  • North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
  • Ries, U. J., Mihm, G. & Narr, B. (1993). J. Med. Chem.36, 4040–4051. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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