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Acta Cryst. (2009). E65, o226    [ doi:10.1107/S1600536808043420 ]

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

B. Xu, L. Yong, D. Wang, R. Zhang and X. Li

Abstract top

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.

Comment top

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.

Related literature top

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

Experimental top

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 top

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.

Computing details top

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

Figures top
[Figure 1] Fig. 1. The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2] Fig. 2. Crystal packing of the title compound with hydrogen bonds drawn as dashed lines.
4-Methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid top
Crystal data top
C12H14N2O2Dx = 1.251 Mg m−3
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 mm−1
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 top
Enraf–Nonuis CAD-4
diffractometer		1304 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 top
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) = 0.195 w = 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 Å−3
133 parametersΔρmin = −0.39 e Å−3
2 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008)
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.039 (3)
Crystal data top
C12H14N2O2Z = 16
Mr = 218.25Mo Kα radiation
Tetragonal, I41/aµ = 0.09 mm−1
a = 12.0548 (17) ÅT = 293 K
c = 31.899 (6) Å0.30 × 0.30 × 0.10 mm
V = 4635.5 (13) Å3
Data collection top
Enraf–Nonuis CAD-4
diffractometer		1304 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.042
Tmin = 0.975, Tmax = 0.991θmax = 25.2°
4426 measured reflections3 standard reflections every 200 reflections
2105 independent reflections intensity decay: none
Refinement top
R[F2 > 2σ(F2)] = 0.072H-atom parameters constrained
wR(F2) = 0.195Δρmax = 0.62 e Å−3
S = 1.00Δρmin = −0.39 e Å−3
2105 reflectionsAbsolute structure: ?
133 parametersFlack parameter: ?
2 restraintsRogers parameter: ?
Special details top

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) top
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) top
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, °) top
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, °) top
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.
Table 1
Hydrogen-bond geometry (Å, °) top
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.
Acknowledgements top

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

references
References top

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