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Acta Crystallogr Sect E Struct Rep Online. 2008 June 1; 64(Pt 6): o1063.
Published online 2008 May 14. doi:  10.1107/S1600536808013408
PMCID: PMC2961411

Methyl 3-amino-4-butanamido-5-methyl­benzoate

Abstract

The title compound, C13H18N2O3, is an inter­mediate in the synthesis of compounds with medicinial applications. The crystal structure is stabilized by inter­molecular N—H(...)O, C—H(...)N and C—H(...)O hydrogen bonds.

Related literature

For bond-length data, see: Allen et al. (1987 [triangle]). For related literature, see: Engeli et al. (2000 [triangle]); Goossens et al. (2003 [triangle]); Kintscher et al. (2004 [triangle]); Kurtz & Pravenec (2004 [triangle]); Ries et al. (1993 [triangle]).

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Object name is e-64-o1063-scheme1.jpg

Experimental

Crystal data

  • C13H18N2O3
  • M r = 250.29
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1063-efi1.jpg
  • a = 10.547 (2) Å
  • b = 16.258 (3) Å
  • c = 8.430 (2) Å
  • β = 111.69 (3)°
  • V = 1343.2 (5) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 293 (2) K
  • 0.40 × 0.20 × 0.10 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.965, T max = 0.991
  • 2579 measured reflections
  • 2404 independent reflections
  • 1511 reflections with I > 2σ(I)
  • R int = 0.028
  • 3 standard reflections every 200 reflections intensity decay: none

Refinement

  • R[F 2 > 2σ(F 2)] = 0.074
  • wR(F 2) = 0.174
  • S = 1.02
  • 2404 reflections
  • 158 parameters
  • H-atom parameters constrained
  • Δρmax = 0.50 e Å−3
  • Δρmin = −0.40 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: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808013408/im2061sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808013408/im2061Isup2.hkl

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

Acknowledgments

The authors thank the Center of Testing and Analysis, Nanjing University, for supporting the data collection.

supplementary crystallographic information

Comment

3-Amino-4-butyrylamino-5-methyl-benzoic acid methyl ester is important as an intermediate in the synthesis of telmisartan, an angiotensin II receptor blocker, and in the development of obesity and related metabolic disorders in diet-induced obese mice (Ries et al., 1993). Telmisartan can be used as a therapeutic tool for metabolic syndrome, including visceral obesity (Engeli et al., 2000; Kintscher et al., 2004; Goossens et al., 2003; Kurtz et al., 2004). As part of our studies in this area, we report herein the synthesis and crystal structure of the title compound, (I).

In the molecule of (I) (Fig. 1), bond lengths and angles are within normal ranges (Allen et al., 1987). The aromatic ring (C3—C8) is, of course, planar.

The crystal structure is stabilized by intermolecular N—H···O, C—H···N and C—H···O hydrogen bonds (Table 1, Fig. 2).

Experimental

4-Amino-3-methyl-benzoic acid methyl ester (8.25 g 50 mmol) was acylated with butyryl chloride (5.3 ml 50 mmol) in chlorobenzene at 373 K. The resulting amide was reacted with fuming nitric acid in sulfuric acid (60%) at 273 K. The resulting 4-(butyrylamino)-3-methyl -5-nitrobenzoic acid methyl ester was reduced with hydrogen (5 bar) and palladium (10% on charcoal) in methanol. Then palladium was filtered by suction. The produce separates as a colourless flocculent solid.

Crystals of (I) suitable for X-ray diffraction were obstained by slow evaporation of an ethanolic solution.

Refinement

H atoms were positioned geometrically, with N—H = 0.86 Å (for NH) and C—H = 0.93, 0.98 and 0.96 Å for aromatic, methene 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.
A packing diagram for (I). Hydrogen bonds are shown as dashed lines.

Crystal data

C13H18N2O3F000 = 536
Mr = 250.29Dx = 1.238 Mg m3
Monoclinic, P21/cMo Kα radiation λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 10.547 (2) Åθ = 10–13º
b = 16.258 (3) ŵ = 0.09 mm1
c = 8.430 (2) ÅT = 293 (2) K
β = 111.69 (3)ºBlock, colourless
V = 1343.2 (5) Å30.40 × 0.20 × 0.10 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometerRint = 0.028
Radiation source: fine-focus sealed tubeθmax = 25.2º
Monochromator: graphiteθmin = 2.1º
T = 293(2) Kh = −12→11
ω/2θ scansk = 0→19
Absorption correction: ψ scan(North et al., 1968)l = 0→10
Tmin = 0.965, Tmax = 0.9913 standard reflections
2579 measured reflections every 200 reflections
2404 independent reflections intensity decay: none
1511 reflections with I > 2σ(I)

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.075H-atom parameters constrained
wR(F2) = 0.174  w = 1/[σ2(Fo2) + (0.05P)2 + 1.5P] where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max = 0.002
2404 reflectionsΔρmax = 0.50 e Å3
158 parametersΔρmin = −0.40 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
N10.7939 (3)0.28652 (17)0.4910 (3)0.0609 (8)
H1A0.78890.28930.38700.073*
O10.9151 (2)0.31431 (18)0.7622 (3)0.0722 (8)
C11.2201 (4)0.4441 (3)0.6344 (6)0.1018 (16)
H1B1.28260.47340.73050.153*
H1C1.17910.48180.54180.153*
H1D1.26850.40230.59940.153*
O20.3477 (2)0.05447 (17)0.6104 (4)0.0760 (8)
N20.7806 (3)0.11598 (19)0.5029 (4)0.0669 (8)
H2A0.77780.06320.50850.080*
H2B0.84690.13950.48450.080*
C21.1113 (4)0.4052 (3)0.6834 (5)0.084
H2C1.15550.37150.78360.100*
H2D1.06300.44870.71630.100*
O30.2717 (2)0.17791 (16)0.6464 (3)0.0690 (7)
C31.0098 (4)0.3540 (2)0.5540 (4)0.0620 (9)
H3A1.05700.30980.52130.074*
H3B0.96450.38720.45330.074*
C40.9036 (3)0.31730 (19)0.6119 (4)0.0483 (8)
C50.6835 (3)0.2489 (2)0.5237 (4)0.0522 (8)
C60.5855 (3)0.2967 (2)0.5521 (4)0.0543 (8)
C70.4796 (3)0.2576 (2)0.5839 (4)0.0537 (8)
H7A0.41410.28880.60610.064*
C80.4715 (3)0.1723 (2)0.5825 (3)0.0479 (8)
C90.5702 (3)0.1258 (2)0.5536 (4)0.0511 (8)
H9A0.56440.06870.55410.061*
C100.6789 (3)0.1628 (2)0.5235 (4)0.0515 (8)
C110.5897 (4)0.3891 (2)0.5480 (5)0.0723 (11)
H11A0.67660.40660.54780.108*
H11B0.57680.41090.64680.108*
H11C0.51850.40880.44670.108*
C120.3588 (3)0.1281 (2)0.6125 (4)0.0540 (8)
C130.1601 (4)0.1399 (3)0.6781 (5)0.0876 (13)
H13A0.10500.18170.70130.131*
H13B0.19530.10380.77460.131*
H13C0.10560.10900.57940.131*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0727 (19)0.078 (2)0.0357 (14)−0.0270 (16)0.0244 (14)−0.0037 (14)
O10.0547 (14)0.120 (2)0.0446 (13)−0.0178 (14)0.0212 (11)−0.0041 (13)
C10.088 (3)0.127 (4)0.099 (3)−0.049 (3)0.044 (3)−0.021 (3)
O20.0629 (16)0.0679 (18)0.106 (2)−0.0081 (13)0.0415 (15)0.0052 (15)
N20.0536 (17)0.074 (2)0.082 (2)−0.0098 (15)0.0355 (16)−0.0048 (17)
C20.0840.0840.0840.0000.0310.000
O30.0547 (14)0.0824 (18)0.0749 (17)−0.0004 (13)0.0296 (13)0.0048 (13)
C30.063 (2)0.072 (2)0.059 (2)−0.0144 (19)0.0328 (18)−0.0081 (18)
C40.0546 (19)0.0550 (19)0.0413 (17)0.0012 (16)0.0248 (15)−0.0036 (15)
C50.056 (2)0.069 (2)0.0284 (15)−0.0165 (17)0.0127 (14)−0.0038 (15)
C60.060 (2)0.060 (2)0.0363 (16)−0.0098 (17)0.0099 (15)0.0002 (15)
C70.0500 (19)0.061 (2)0.0455 (18)−0.0014 (16)0.0124 (15)0.0019 (16)
C80.0437 (17)0.061 (2)0.0325 (15)−0.0059 (15)0.0059 (13)0.0010 (14)
C90.0435 (18)0.0570 (19)0.0483 (18)−0.0042 (15)0.0118 (15)0.0038 (15)
C100.0456 (18)0.066 (2)0.0382 (16)−0.0081 (16)0.0102 (14)−0.0020 (15)
C110.082 (3)0.067 (2)0.066 (2)−0.010 (2)0.025 (2)0.0051 (19)
C120.0473 (19)0.069 (2)0.0418 (17)0.0004 (18)0.0121 (15)0.0052 (17)
C130.063 (2)0.123 (4)0.093 (3)0.004 (2)0.048 (2)0.020 (3)

Geometric parameters (Å, °)

N1—C41.325 (4)C3—H3A0.9700
N1—C51.430 (4)C3—H3B0.9700
N1—H1A0.8600C5—C61.384 (5)
O1—C41.229 (3)C5—C101.400 (5)
C1—C21.496 (5)C6—C71.394 (4)
C1—H1B0.9600C6—C111.503 (5)
C1—H1C0.9600C7—C81.391 (4)
C1—H1D0.9600C7—H7A0.9300
O2—C121.202 (4)C8—C91.379 (4)
N2—C101.378 (4)C8—C121.488 (4)
N2—H2A0.8600C9—C101.399 (4)
N2—H2B0.8600C9—H9A0.9300
C2—C31.472 (5)C11—H11A0.9600
C2—H2C0.9700C11—H11B0.9600
C2—H2D0.9700C11—H11C0.9600
O3—C121.333 (4)C13—H13A0.9600
O3—C131.439 (4)C13—H13B0.9600
C3—C41.500 (4)C13—H13C0.9600
C4—N1—C5123.7 (2)C5—C6—C7118.6 (3)
C4—N1—H1A118.1C5—C6—C11121.8 (3)
C5—N1—H1A118.1C7—C6—C11119.5 (3)
C2—C1—H1B109.5C8—C7—C6120.3 (3)
C2—C1—H1C109.5C8—C7—H7A119.8
H1B—C1—H1C109.5C6—C7—H7A119.8
C2—C1—H1D109.5C9—C8—C7120.0 (3)
H1B—C1—H1D109.5C9—C8—C12117.9 (3)
H1C—C1—H1D109.5C7—C8—C12122.1 (3)
C10—N2—H2A120.0C8—C9—C10121.3 (3)
C10—N2—H2B120.0C8—C9—H9A119.4
H2A—N2—H2B120.0C10—C9—H9A119.4
C3—C2—C1117.2 (3)N2—C10—C9120.9 (3)
C3—C2—H2C108.0N2—C10—C5121.7 (3)
C1—C2—H2C108.0C9—C10—C5117.4 (3)
C3—C2—H2D108.0C6—C11—H11A109.5
C1—C2—H2D108.0C6—C11—H11B109.5
H2C—C2—H2D107.2H11A—C11—H11B109.5
C12—O3—C13117.1 (3)C6—C11—H11C109.5
C2—C3—C4114.2 (3)H11A—C11—H11C109.5
C2—C3—H3A108.7H11B—C11—H11C109.5
C4—C3—H3A108.7O2—C12—O3122.5 (3)
C2—C3—H3B108.7O2—C12—C8123.9 (3)
C4—C3—H3B108.7O3—C12—C8113.6 (3)
H3A—C3—H3B107.6O3—C13—H13A109.5
O1—C4—N1120.2 (3)O3—C13—H13B109.5
O1—C4—C3123.4 (3)H13A—C13—H13B109.5
N1—C4—C3116.4 (3)O3—C13—H13C109.5
C6—C5—C10122.3 (3)H13A—C13—H13C109.5
C6—C5—N1120.4 (3)H13B—C13—H13C109.5
C10—C5—N1117.2 (3)
C1—C2—C3—C4−179.7 (4)C7—C8—C9—C10−0.7 (4)
C5—N1—C4—O10.2 (5)C12—C8—C9—C10179.7 (3)
C5—N1—C4—C3179.6 (3)C8—C9—C10—N2176.8 (3)
C2—C3—C4—O1−15.3 (5)C8—C9—C10—C50.0 (4)
C2—C3—C4—N1165.4 (3)C6—C5—C10—N2−176.9 (3)
C4—N1—C5—C679.5 (4)N1—C5—C10—N23.8 (4)
C4—N1—C5—C10−101.3 (4)C6—C5—C10—C9−0.1 (5)
C10—C5—C6—C70.9 (5)N1—C5—C10—C9−179.3 (2)
N1—C5—C6—C7−179.9 (3)C13—O3—C12—O2−1.1 (5)
C10—C5—C6—C11−178.5 (3)C13—O3—C12—C8−179.6 (3)
N1—C5—C6—C110.7 (5)C9—C8—C12—O2−1.2 (5)
C5—C6—C7—C8−1.6 (5)C7—C8—C12—O2179.2 (3)
C11—C6—C7—C8177.8 (3)C9—C8—C12—O3177.3 (3)
C6—C7—C8—C91.6 (5)C7—C8—C12—O3−2.4 (4)
C6—C7—C8—C12−178.8 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.862.603.141 (4)122
N2—H2A···O2ii0.862.333.077 (4)145
N2—H2B···N10.862.462.780 (4)103
N2—H2B···O1i0.862.363.089 (4)142
C11—H11A···N10.962.452.901 (5)108

Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+1, −y, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IM2061).

References

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  • 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]
  • Kurtz, T. W. & Pravenec, M. (2004). J. Hypertens 22, 2253–2261. [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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