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

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

doi:10.1107/S1600536808013408

organic compounds

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ISSN: 2056-9890

Volume 64| Part 6| June 2008| Page o1063

doi:10.1107/S1600536808013408

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

Xiang Li,^a Lian-shan Yuan,^a Dan Wang ^b and Cheng Yao ^a ^*

^aDepartment of Applied Chemistry, College of Sciences, Nanjing University of Technolgy, Xinmofan Road No. 5, Nanjing 210009, People's Republic of China, and ^bBioengineering Department, Xuzhou Higher Vocational College of Bioengineering, Mine West Road, Xuzhou 221006, People's Republic of China
^*Correspondence e-mail: yaocheng@njut.edu.cn

(Received 15 March 2008; accepted 6 May 2008; online 14 May 2008)

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 ). For related literature, see: Engeli et al. (2000 ); Goossens et al. (2003 ); Kintscher et al. (2004 ); Kurtz & Pravenec (2004 ); Ries et al. (1993 ).

Experimental

Crystal data

C₁₃H₁₈N₂O₃
M_r = 250.29
Monoclinic, P 2₁ /c
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 ) 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[F² > 2σ(F²)] = 0.074
wR(F²) = 0.174
S = 1.02
2404 reflections
158 parameters
H-atom parameters constrained
Δρ_max = 0.50 e Å⁻³
Δρ_min = −0.40 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1ⁱ	0.86	2.60	3.141 (4)	122
N2—H2A⋯O2ⁱⁱ	0.86	2.33	3.077 (4)	145
N2—H2B⋯N1	0.86	2.46	2.780 (4)	103
N2—H2B⋯O1ⁱ	0.86	2.36	3.089 (4)	142
C11—H11A⋯N1	0.96	2.45	2.901 (5)	108
Symmetry codes: (i) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (ii) -x+1, -y, -z+1.

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ); cell refinement: CAD-4 Software; 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: SHELXL97.

Supporting information

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

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

checkCIF report

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.

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

	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.

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

Crystal data top

C₁₃H₁₈N₂O₃	F(000) = 536
M_r = 250.29	D_x = 1.238 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 10.547 (2) Å	θ = 10–13°
b = 16.258 (3) Å	µ = 0.09 mm⁻¹
c = 8.430 (2) Å	T = 293 K
β = 111.69 (3)°	Block, colourless
V = 1343.2 (5) Å³	0.40 × 0.20 × 0.10 mm
Z = 4

Data collection top

Enraf–Nonius CAD-4 diffractometer	1511 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.028
Graphite monochromator	θ_max = 25.2°, θ_min = 2.1°
ω/2θ scans	h = −12→11
Absorption correction: ψ scan (North et al., 1968)	k = 0→19
T_min = 0.965, T_max = 0.991	l = 0→10
2579 measured reflections	3 standard reflections every 200 reflections
2404 independent reflections	intensity decay: none

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.075	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.174	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.05P)² + 1.5P] where P = (F_o² + 2F_c²)/3
2404 reflections	(Δ/σ)_max = 0.002
158 parameters	Δρ_max = 0.50 e Å⁻³
0 restraints	Δρ_min = −0.40 e Å⁻³

Crystal data top

C₁₃H₁₈N₂O₃	V = 1343.2 (5) Å³
M_r = 250.29	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 10.547 (2) Å	µ = 0.09 mm⁻¹
b = 16.258 (3) Å	T = 293 K
c = 8.430 (2) Å	0.40 × 0.20 × 0.10 mm
β = 111.69 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	1511 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.028
T_min = 0.965, T_max = 0.991	3 standard reflections every 200 reflections
2579 measured reflections	intensity decay: none
2404 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.075	0 restraints
wR(F²) = 0.174	H-atom parameters constrained
S = 1.02	Δρ_max = 0.50 e Å⁻³
2404 reflections	Δρ_min = −0.40 e Å⁻³
158 parameters

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

	x	y	z	U_iso*/U_eq
N1	0.7939 (3)	0.28652 (17)	0.4910 (3)	0.0609 (8)
H1A	0.7889	0.2893	0.3870	0.073*
O1	0.9151 (2)	0.31431 (18)	0.7622 (3)	0.0722 (8)
C1	1.2201 (4)	0.4441 (3)	0.6344 (6)	0.1018 (16)
H1B	1.2826	0.4734	0.7305	0.153*
H1C	1.1791	0.4818	0.5418	0.153*
H1D	1.2685	0.4023	0.5994	0.153*
O2	0.3477 (2)	0.05447 (17)	0.6104 (4)	0.0760 (8)
N2	0.7806 (3)	0.11598 (19)	0.5029 (4)	0.0669 (8)
H2A	0.7778	0.0632	0.5085	0.080*
H2B	0.8469	0.1395	0.4845	0.080*
C2	1.1113 (4)	0.4052 (3)	0.6834 (5)	0.084
H2C	1.1555	0.3715	0.7836	0.100*
H2D	1.0630	0.4487	0.7163	0.100*
O3	0.2717 (2)	0.17791 (16)	0.6464 (3)	0.0690 (7)
C3	1.0098 (4)	0.3540 (2)	0.5540 (4)	0.0620 (9)
H3A	1.0570	0.3098	0.5213	0.074*
H3B	0.9645	0.3872	0.4533	0.074*
C4	0.9036 (3)	0.31730 (19)	0.6119 (4)	0.0483 (8)
C5	0.6835 (3)	0.2489 (2)	0.5237 (4)	0.0522 (8)
C6	0.5855 (3)	0.2967 (2)	0.5521 (4)	0.0543 (8)
C7	0.4796 (3)	0.2576 (2)	0.5839 (4)	0.0537 (8)
H7A	0.4141	0.2888	0.6061	0.064*
C8	0.4715 (3)	0.1723 (2)	0.5825 (3)	0.0479 (8)
C9	0.5702 (3)	0.1258 (2)	0.5536 (4)	0.0511 (8)
H9A	0.5644	0.0687	0.5541	0.061*
C10	0.6789 (3)	0.1628 (2)	0.5235 (4)	0.0515 (8)
C11	0.5897 (4)	0.3891 (2)	0.5480 (5)	0.0723 (11)
H11A	0.6766	0.4066	0.5478	0.108*
H11B	0.5768	0.4109	0.6468	0.108*
H11C	0.5185	0.4088	0.4467	0.108*
C12	0.3588 (3)	0.1281 (2)	0.6125 (4)	0.0540 (8)
C13	0.1601 (4)	0.1399 (3)	0.6781 (5)	0.0876 (13)
H13A	0.1050	0.1817	0.7013	0.131*
H13B	0.1953	0.1038	0.7746	0.131*
H13C	0.1056	0.1090	0.5794	0.131*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0727 (19)	0.078 (2)	0.0357 (14)	−0.0270 (16)	0.0244 (14)	−0.0037 (14)
O1	0.0547 (14)	0.120 (2)	0.0446 (13)	−0.0178 (14)	0.0212 (11)	−0.0041 (13)
C1	0.088 (3)	0.127 (4)	0.099 (3)	−0.049 (3)	0.044 (3)	−0.021 (3)
O2	0.0629 (16)	0.0679 (18)	0.106 (2)	−0.0081 (13)	0.0415 (15)	0.0052 (15)
N2	0.0536 (17)	0.074 (2)	0.082 (2)	−0.0098 (15)	0.0355 (16)	−0.0048 (17)
C2	0.084	0.084	0.084	0.000	0.031	0.000
O3	0.0547 (14)	0.0824 (18)	0.0749 (17)	−0.0004 (13)	0.0296 (13)	0.0048 (13)
C3	0.063 (2)	0.072 (2)	0.059 (2)	−0.0144 (19)	0.0328 (18)	−0.0081 (18)
C4	0.0546 (19)	0.0550 (19)	0.0413 (17)	0.0012 (16)	0.0248 (15)	−0.0036 (15)
C5	0.056 (2)	0.069 (2)	0.0284 (15)	−0.0165 (17)	0.0127 (14)	−0.0038 (15)
C6	0.060 (2)	0.060 (2)	0.0363 (16)	−0.0098 (17)	0.0099 (15)	0.0002 (15)
C7	0.0500 (19)	0.061 (2)	0.0455 (18)	−0.0014 (16)	0.0124 (15)	0.0019 (16)
C8	0.0437 (17)	0.061 (2)	0.0325 (15)	−0.0059 (15)	0.0059 (13)	0.0010 (14)
C9	0.0435 (18)	0.0570 (19)	0.0483 (18)	−0.0042 (15)	0.0118 (15)	0.0038 (15)
C10	0.0456 (18)	0.066 (2)	0.0382 (16)	−0.0081 (16)	0.0102 (14)	−0.0020 (15)
C11	0.082 (3)	0.067 (2)	0.066 (2)	−0.010 (2)	0.025 (2)	0.0051 (19)
C12	0.0473 (19)	0.069 (2)	0.0418 (17)	0.0004 (18)	0.0121 (15)	0.0052 (17)
C13	0.063 (2)	0.123 (4)	0.093 (3)	0.004 (2)	0.048 (2)	0.020 (3)

Geometric parameters (Å, º) top

N1—C4	1.325 (4)	C3—H3A	0.9700
N1—C5	1.430 (4)	C3—H3B	0.9700
N1—H1A	0.8600	C5—C6	1.384 (5)
O1—C4	1.229 (3)	C5—C10	1.400 (5)
C1—C2	1.496 (5)	C6—C7	1.394 (4)
C1—H1B	0.9600	C6—C11	1.503 (5)
C1—H1C	0.9600	C7—C8	1.391 (4)
C1—H1D	0.9600	C7—H7A	0.9300
O2—C12	1.202 (4)	C8—C9	1.379 (4)
N2—C10	1.378 (4)	C8—C12	1.488 (4)
N2—H2A	0.8600	C9—C10	1.399 (4)
N2—H2B	0.8600	C9—H9A	0.9300
C2—C3	1.472 (5)	C11—H11A	0.9600
C2—H2C	0.9700	C11—H11B	0.9600
C2—H2D	0.9700	C11—H11C	0.9600
O3—C12	1.333 (4)	C13—H13A	0.9600
O3—C13	1.439 (4)	C13—H13B	0.9600
C3—C4	1.500 (4)	C13—H13C	0.9600

C4—N1—C5	123.7 (2)	C5—C6—C7	118.6 (3)
C4—N1—H1A	118.1	C5—C6—C11	121.8 (3)
C5—N1—H1A	118.1	C7—C6—C11	119.5 (3)
C2—C1—H1B	109.5	C8—C7—C6	120.3 (3)
C2—C1—H1C	109.5	C8—C7—H7A	119.8
H1B—C1—H1C	109.5	C6—C7—H7A	119.8
C2—C1—H1D	109.5	C9—C8—C7	120.0 (3)
H1B—C1—H1D	109.5	C9—C8—C12	117.9 (3)
H1C—C1—H1D	109.5	C7—C8—C12	122.1 (3)
C10—N2—H2A	120.0	C8—C9—C10	121.3 (3)
C10—N2—H2B	120.0	C8—C9—H9A	119.4
H2A—N2—H2B	120.0	C10—C9—H9A	119.4
C3—C2—C1	117.2 (3)	N2—C10—C9	120.9 (3)
C3—C2—H2C	108.0	N2—C10—C5	121.7 (3)
C1—C2—H2C	108.0	C9—C10—C5	117.4 (3)
C3—C2—H2D	108.0	C6—C11—H11A	109.5
C1—C2—H2D	108.0	C6—C11—H11B	109.5
H2C—C2—H2D	107.2	H11A—C11—H11B	109.5
C12—O3—C13	117.1 (3)	C6—C11—H11C	109.5
C2—C3—C4	114.2 (3)	H11A—C11—H11C	109.5
C2—C3—H3A	108.7	H11B—C11—H11C	109.5
C4—C3—H3A	108.7	O2—C12—O3	122.5 (3)
C2—C3—H3B	108.7	O2—C12—C8	123.9 (3)
C4—C3—H3B	108.7	O3—C12—C8	113.6 (3)
H3A—C3—H3B	107.6	O3—C13—H13A	109.5
O1—C4—N1	120.2 (3)	O3—C13—H13B	109.5
O1—C4—C3	123.4 (3)	H13A—C13—H13B	109.5
N1—C4—C3	116.4 (3)	O3—C13—H13C	109.5
C6—C5—C10	122.3 (3)	H13A—C13—H13C	109.5
C6—C5—N1	120.4 (3)	H13B—C13—H13C	109.5
C10—C5—N1	117.2 (3)

C1—C2—C3—C4	−179.7 (4)	C7—C8—C9—C10	−0.7 (4)
C5—N1—C4—O1	0.2 (5)	C12—C8—C9—C10	179.7 (3)
C5—N1—C4—C3	179.6 (3)	C8—C9—C10—N2	176.8 (3)
C2—C3—C4—O1	−15.3 (5)	C8—C9—C10—C5	0.0 (4)
C2—C3—C4—N1	165.4 (3)	C6—C5—C10—N2	−176.9 (3)
C4—N1—C5—C6	79.5 (4)	N1—C5—C10—N2	3.8 (4)
C4—N1—C5—C10	−101.3 (4)	C6—C5—C10—C9	−0.1 (5)
C10—C5—C6—C7	0.9 (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—C11	0.7 (5)	C9—C8—C12—O2	−1.2 (5)
C5—C6—C7—C8	−1.6 (5)	C7—C8—C12—O2	179.2 (3)
C11—C6—C7—C8	177.8 (3)	C9—C8—C12—O3	177.3 (3)
C6—C7—C8—C9	1.6 (5)	C7—C8—C12—O3	−2.4 (4)
C6—C7—C8—C12	−178.8 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱ	0.86	2.60	3.141 (4)	122
N2—H2A···O2ⁱⁱ	0.86	2.33	3.077 (4)	145
N2—H2B···N1	0.86	2.46	2.780 (4)	103
N2—H2B···O1ⁱ	0.86	2.36	3.089 (4)	142
C11—H11A···N1	0.96	2.45	2.901 (5)	108

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

Experimental details

Crystal data
Chemical formula	C₁₃H₁₈N₂O₃
M_r	250.29
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	10.547 (2), 16.258 (3), 8.430 (2)
β (°)	111.69 (3)
V (Å³)	1343.2 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.40 × 0.20 × 0.10

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.965, 0.991
No. of measured, independent and observed [I > 2σ(I)] reflections	2579, 2404, 1511
R_int	0.028
(sin θ/λ)_max (Å⁻¹)	0.598

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.075, 0.174, 1.02
No. of reflections	2404
No. of parameters	158
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.50, −0.40

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), XCAD4 (Harms & Wocadlo,1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱ	0.8600	2.6000	3.141 (4)	122.00
N2—H2A···O2ⁱⁱ	0.8600	2.3300	3.077 (4)	145.00
N2—H2B···N1	0.8600	2.4600	2.780 (4)	103.00
N2—H2B···O1ⁱ	0.8600	2.3600	3.089 (4)	142.00
C11—H11A···N1	0.9600	2.4500	2.901 (5)	108.00

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

Acknowledgements

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

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. 1–19. CrossRef Web of Science Google Scholar
Engeli, S., Negrel, R. & Sharma, A. M. (2000). Hypertension 35, 1270–1277. Web of Science CrossRef PubMed CAS Google Scholar
Enraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands. Google Scholar
Goossens, G. H., Blaak, E. E. & Baak, M. A. (2003). Obes. Rev. 4, 43–55. CrossRef PubMed CAS Google Scholar
Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany. Google Scholar
Kintscher, U., Lyon, C. J. & Law, R. E. (2004). Front. Biosci. 9, 359–369. Web of Science CrossRef PubMed CAS Google Scholar
Kurtz, T. W. & Pravenec, M. (2004). J. Hypertens. 22, 2253–2261. Web of Science CrossRef PubMed CAS Google Scholar
North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359. CrossRef IUCr Journals Web of Science Google Scholar
Ries, U. J., Mihm, G. & Narr, B. (1993). J. Med. Chem. 36, 4040–4051. CrossRef CAS PubMed Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar