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Acta Cryst. (2008). E64, o1063    [ doi:10.1107/S1600536808013408 ]

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

X. Li, L. Yuan, D. Wang and C. Yao

Abstract top

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.

Comment top

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).

Related literature top

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

Experimental top

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 top

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.

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: SHELXS97 (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. A packing diagram for (I). Hydrogen bonds are shown as dashed lines.
Methyl 3-amino-4-butanamido-5-methylbenzoate top
Crystal data top
C13H18N2O3F000 = 536
Mr = 250.29Dx = 1.238 Mg m−3
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 mm−1
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 top
Enraf–Nonius CAD-4
diffractometer		Rint = 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 top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.075H-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 Å−3
158 parametersΔρmin = −0.40 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C13H18N2O3V = 1343.2 (5) Å3
Mr = 250.29Z = 4
Monoclinic, P21/cMo Kα
a = 10.547 (2) ŵ = 0.09 mm−1
b = 16.258 (3) ÅT = 293 (2) K
c = 8.430 (2) Å0.40 × 0.20 × 0.10 mm
β = 111.69 (3)º
Data collection top
Enraf–Nonius CAD-4
diffractometer		1511 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.028
Tmin = 0.965, Tmax = 0.9913 standard reflections
2579 measured reflections every 200 reflections
2404 independent reflections intensity decay: none
Refinement top
R[F2 > 2σ(F2)] = 0.075158 parameters
wR(F2) = 0.174H-atom parameters constrained
S = 1.02Δρmax = 0.50 e Å−3
2404 reflectionsΔρmin = −0.40 e Å−3
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
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) top
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, °) top
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, °) top
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.
Table 1
Hydrogen-bond geometry (Å, °) top
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.
Acknowledgements top

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

references
References top

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