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Acta Cryst. (2008). E64, o785    [ doi:10.1107/S1600536808005989 ]

Ethyl 4-amino-3-methylbenzoate

W.-L. Song, D. Wang, X.-H. Li and D.-C. Wang

Abstract top

The asymmetric unit of the title compound, C10H13NO2, contains two molecules which are linked via an N-H...N hydrogen bonds to form a dimer. These dimers are further linked via N-H...O intermolecular hydrogen bonds.

Comment top

Ethyl 3-methyl-4-aminobenzoate is a material for preparing the important intermidates of bis-(2-haloethyl)aminophenyl substituted distamycin derivatives(Baraldi et al., 2007), which are used as antitumor alkylating and antiviral agents related to the known antibiotic distamycin A (Baraldi et al., 1999). Distamycin A belongs to the family of the pyrroleamidine antibiotics (Baraldi et al., 2000) and is reported to interact reversibly and selectively with DNA-AT sequences interfering with both replication and transcription (Baraldi et al., 2003). Bis-(2-haloethyl)aminophenyl substituted distamycin derivatives can therefore be used in a treatment to ameliorate a cancer (Wang et al., 2003). They may be administered to improve the condition of a patient having a leukaemia lymphoma, sarcoma, such as myeloblastic leukaemia, neuroblastoma, Wilm's tumor or malignant neoplasm of the bladder, breast, lung or thyroid. (Zaffaroni et al., 2002).

The molecular structure of (I) is shown in Fig. 1. The bond lengths and angles are within normal ranges (Allen et al., 1987).

The asymmetric unit of the title compound, contains two molecules which are linked via N—H···N hydrogen bonds to form dimers. In the crystals, molecules are linked via N—H···O Intermolecular hydrogen bonds (Table 1), which may be effective in the stabilization of the crystals.

Related literature top

For related literature, see: Baraldi et al. (1999, 2000, 2003, 2007); Wang et al. (2003); Zaffaroni et al. (2002). For bond-length data, see: Allen et al. (1987).

Experimental top

The title compound was prepared from 3-Methyl-4-aminobenzoic acid (15.2 g, 100 mmole) in ethanol (40.4 ml, 1000 mmole). After the solid has melted, concentrated hydrochloric acid (142 g, 120 ml) was added dropwise from a dropping funnel at 90°C, the the reaction mixture was cooled with ice and water and finaly the product was filtered by suction. Suitable crystals were obtained by evaporation of a methanol solution for about 3 d.

Refinement top

All H atoms were placed geometrically at the distances of 0.93–0.97 Å for C—H and 0.86 Å for N—H and included in the refinement in riding motion approximation with Uiso(H) = 1.2 or 1.5Ueq of the carrier atom.

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: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. A view of the molecular structure of (I), showing displacement ellipsoids at the 50% probability level. N—H···N hydrogen bonds are shown as dashed lines.
Ethyl 4-amino-3-methylbenzoate top
Crystal data top
C10H13NO2Z = 4
Mr = 179.21F000 = 384
Triclinic, P1Dx = 1.190 Mg m−3
Hall symbol: -P 1Mo Kα radiation
λ = 0.71073 Å
a = 8.0110 (16) ÅCell parameters from 25 reflections
b = 8.7030 (17) Åθ = 10–14º
c = 15.835 (3) ŵ = 0.08 mm−1
α = 90.78 (3)ºT = 298 (2) K
β = 95.13 (3)ºBlock, colorless
γ = 114.34 (3)º0.30 × 0.20 × 0.10 mm
V = 1000.3 (3) Å3
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.052
Radiation source: fine-focus sealed tubeθmax = 25.2º
Monochromator: graphiteθmin = 1.3º
T = 298(2) Kh = −9→9
ω/2θ scansk = −10→10
Absorption correction: ψ scan
(North et al., 1968)		l = 0→18
Tmin = 0.975, Tmax = 0.9913 standard reflections
3874 measured reflections every 200 reflections
3594 independent reflections intensity decay: none
2146 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) = 0.177  w = 1/[σ2(Fo2) + (0.04P)2 + 1.2P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max < 0.001
3594 reflectionsΔρmax = 0.23 e Å−3
235 parametersΔρmin = −0.22 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C10H13NO2γ = 114.34 (3)º
Mr = 179.21V = 1000.3 (3) Å3
Triclinic, P1Z = 4
a = 8.0110 (16) ÅMo Kα
b = 8.7030 (17) ŵ = 0.08 mm−1
c = 15.835 (3) ÅT = 298 (2) K
α = 90.78 (3)º0.30 × 0.20 × 0.10 mm
β = 95.13 (3)º
Data collection top
Enraf–Nonius CAD-4
diffractometer		2146 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.052
Tmin = 0.975, Tmax = 0.9913 standard reflections
3874 measured reflections every 200 reflections
3594 independent reflections intensity decay: none
Refinement top
R[F2 > 2σ(F2)] = 0.075235 parameters
wR(F2) = 0.177H-atom parameters constrained
S = 1.02Δρmax = 0.23 e Å−3
3594 reflectionsΔρmin = −0.22 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
O11.2476 (4)0.4839 (3)1.01662 (15)0.0684 (7)
O21.2577 (4)0.5912 (3)0.88836 (15)0.0742 (8)
N10.5942 (5)−0.1423 (4)0.8227 (2)0.0872 (11)
H1A0.5484−0.21920.85800.105*
H1B0.5509−0.16040.77010.105*
C11.4390 (7)0.6205 (6)1.1432 (2)0.0884 (13)
H1C1.53890.72201.16740.133*
H1D1.47180.52671.15050.133*
H1E1.33110.60121.17120.133*
C21.3999 (6)0.6384 (5)1.0501 (2)0.0695 (10)
H2A1.36810.73381.04200.083*
H2B1.50770.65711.02110.083*
C31.1842 (5)0.4730 (4)0.9338 (2)0.0549 (8)
C41.0343 (5)0.3145 (4)0.9073 (2)0.0514 (8)
C50.9506 (5)0.1886 (4)0.9638 (2)0.0620 (10)
H5A0.99320.20721.02120.074*
C60.8093 (5)0.0413 (4)0.9358 (2)0.0629 (10)
H6A0.7590−0.04100.97430.075*
C70.7362 (5)0.0087 (4)0.8503 (2)0.0607 (9)
C80.8176 (5)0.1308 (4)0.7910 (2)0.0579 (9)
C90.9597 (5)0.2792 (4)0.8216 (2)0.0537 (8)
H9A1.01030.36200.78340.064*
C100.7439 (6)0.0996 (5)0.6984 (2)0.0790 (12)
H10A0.81840.19260.66720.119*
H10B0.61920.08890.69240.119*
H10C0.7471−0.00260.67670.119*
O30.2589 (4)0.2954 (3)0.47872 (15)0.0695 (7)
O40.1772 (4)0.3743 (3)0.59841 (17)0.0836 (9)
N20.2153 (5)−0.3189 (4)0.69728 (19)0.0828 (11)
H2C0.1979−0.33800.74960.099*
H2D0.2337−0.39030.66560.099*
C110.3055 (7)0.4392 (6)0.3509 (3)0.0990 (15)
H11A0.30720.53700.32290.149*
H11B0.21520.33910.32040.149*
H11C0.42480.43750.35230.149*
C120.2570 (6)0.4456 (5)0.4406 (2)0.0764 (11)
H12A0.34650.54660.47220.092*
H12B0.13600.44610.44030.092*
C130.2119 (5)0.2726 (5)0.5596 (2)0.0608 (9)
C140.2194 (5)0.1199 (4)0.59291 (19)0.0543 (8)
C150.1854 (5)0.0871 (4)0.6782 (2)0.0545 (8)
H15A0.16320.16490.71080.065*
C160.1840 (5)−0.0559 (4)0.7146 (2)0.0549 (8)
C170.2137 (5)−0.1753 (4)0.6644 (2)0.0597 (9)
C180.2476 (6)−0.1425 (5)0.5793 (2)0.0682 (11)
H18A0.2686−0.22000.54580.082*
C190.2499 (5)0.0029 (5)0.5451 (2)0.0660 (10)
H19A0.27240.02210.48870.079*
C200.1455 (6)−0.0876 (5)0.8067 (2)0.0768 (12)
H20A0.12790.00550.83120.115*
H20B0.2479−0.09860.83790.115*
H20C0.0363−0.18970.80890.115*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0901 (18)0.0660 (16)0.0515 (14)0.0347 (14)0.0056 (13)0.0157 (12)
O20.100 (2)0.0594 (15)0.0596 (16)0.0282 (14)0.0118 (14)0.0263 (13)
N10.099 (3)0.072 (2)0.078 (2)0.021 (2)0.013 (2)0.0202 (18)
C10.114 (4)0.099 (3)0.063 (3)0.059 (3)−0.010 (2)−0.008 (2)
C20.090 (3)0.060 (2)0.067 (2)0.040 (2)0.000 (2)0.0075 (19)
C30.068 (2)0.055 (2)0.051 (2)0.0334 (18)0.0094 (17)0.0118 (16)
C40.068 (2)0.0485 (19)0.0467 (18)0.0319 (17)0.0108 (16)0.0142 (15)
C50.087 (3)0.060 (2)0.048 (2)0.037 (2)0.0177 (18)0.0259 (17)
C60.078 (3)0.057 (2)0.057 (2)0.030 (2)0.0191 (19)0.0255 (18)
C70.072 (2)0.049 (2)0.067 (2)0.0285 (18)0.0145 (19)0.0180 (17)
C80.073 (2)0.062 (2)0.049 (2)0.0373 (19)0.0100 (17)0.0149 (17)
C90.073 (2)0.0505 (19)0.0439 (18)0.0305 (18)0.0133 (16)0.0173 (15)
C100.096 (3)0.076 (3)0.056 (2)0.026 (2)0.006 (2)0.012 (2)
O30.0994 (19)0.0705 (16)0.0524 (15)0.0462 (15)0.0200 (13)0.0246 (12)
O40.140 (3)0.0684 (17)0.0626 (17)0.0603 (18)0.0224 (16)0.0110 (14)
N20.148 (3)0.070 (2)0.0511 (18)0.065 (2)0.0102 (19)0.0136 (16)
C110.135 (4)0.104 (4)0.066 (3)0.053 (3)0.022 (3)0.038 (3)
C120.102 (3)0.068 (2)0.066 (3)0.041 (2)0.012 (2)0.027 (2)
C130.077 (2)0.064 (2)0.047 (2)0.034 (2)0.0102 (17)0.0113 (17)
C140.072 (2)0.055 (2)0.0380 (17)0.0288 (17)0.0062 (15)0.0088 (15)
C150.079 (2)0.056 (2)0.0427 (18)0.0406 (18)0.0107 (16)0.0082 (15)
C160.076 (2)0.061 (2)0.0390 (17)0.0380 (18)0.0113 (16)0.0099 (15)
C170.094 (3)0.055 (2)0.0438 (19)0.045 (2)0.0064 (17)0.0099 (15)
C180.117 (3)0.064 (2)0.0439 (19)0.057 (2)0.011 (2)0.0021 (17)
C190.099 (3)0.069 (2)0.0382 (18)0.041 (2)0.0134 (18)0.0084 (17)
C200.120 (3)0.095 (3)0.042 (2)0.068 (3)0.022 (2)0.0199 (19)
Geometric parameters (Å, °) top
O1—C31.351 (4)O3—C131.362 (4)
O1—C21.446 (4)O3—C121.452 (4)
O2—C31.232 (4)O4—C131.207 (4)
N1—C71.369 (5)N2—C171.365 (4)
N1—H1A0.8600N2—H2C0.8600
N1—H1B0.8600N2—H2D0.8600
C1—C21.503 (5)C11—C121.513 (5)
C1—H1C0.9600C11—H11A0.9600
C1—H1D0.9600C11—H11B0.9600
C1—H1E0.9600C11—H11C0.9600
C2—H2A0.9700C12—H12A0.9700
C2—H2B0.9700C12—H12B0.9700
C3—C41.432 (5)C13—C141.458 (5)
C4—C51.407 (4)C14—C191.374 (5)
C4—C91.409 (4)C14—C151.411 (4)
C5—C61.349 (5)C15—C161.375 (4)
C5—H5A0.9300C15—H15A0.9300
C6—C71.404 (5)C16—C171.409 (4)
C6—H6A0.9300C16—C201.522 (4)
C7—C81.414 (5)C17—C181.409 (4)
C8—C91.367 (5)C18—C191.376 (5)
C8—C101.509 (5)C18—H18A0.9300
C9—H9A0.9300C19—H19A0.9300
C10—H10A0.9600C20—H20A0.9600
C10—H10B0.9600C20—H20B0.9600
C10—H10C0.9600C20—H20C0.9600
C3—O1—C2118.2 (3)C13—O3—C12116.0 (3)
C7—N1—H1A120.0C17—N2—H2C120.0
C7—N1—H1B120.0C17—N2—H2D120.0
H1A—N1—H1B120.0H2C—N2—H2D120.0
C2—C1—H1C109.5C12—C11—H11A109.5
C2—C1—H1D109.5C12—C11—H11B109.5
H1C—C1—H1D109.5H11A—C11—H11B109.5
C2—C1—H1E109.5C12—C11—H11C109.5
H1C—C1—H1E109.5H11A—C11—H11C109.5
H1D—C1—H1E109.5H11B—C11—H11C109.5
O1—C2—C1107.6 (3)O3—C12—C11106.2 (3)
O1—C2—H2A110.2O3—C12—H12A110.5
C1—C2—H2A110.2C11—C12—H12A110.5
O1—C2—H2B110.2O3—C12—H12B110.5
C1—C2—H2B110.2C11—C12—H12B110.5
H2A—C2—H2B108.5H12A—C12—H12B108.7
O2—C3—O1120.3 (3)O4—C13—O3121.9 (3)
O2—C3—C4126.2 (3)O4—C13—C14125.8 (3)
O1—C3—C4113.5 (3)O3—C13—C14112.2 (3)
C5—C4—C9116.4 (3)C19—C14—C15118.2 (3)
C5—C4—C3123.1 (3)C19—C14—C13123.8 (3)
C9—C4—C3120.5 (3)C15—C14—C13118.0 (3)
C6—C5—C4121.0 (3)C16—C15—C14122.3 (3)
C6—C5—H5A119.5C16—C15—H15A118.8
C4—C5—H5A119.5C14—C15—H15A118.8
C5—C6—C7121.8 (3)C15—C16—C17118.7 (3)
C5—C6—H6A119.1C15—C16—C20120.9 (3)
C7—C6—H6A119.1C17—C16—C20120.4 (3)
N1—C7—C6121.1 (3)N2—C17—C16121.3 (3)
N1—C7—C8119.7 (3)N2—C17—C18119.7 (3)
C6—C7—C8119.1 (3)C16—C17—C18119.0 (3)
C9—C8—C7117.5 (3)C19—C18—C17120.8 (3)
C9—C8—C10121.9 (3)C19—C18—H18A119.6
C7—C8—C10120.6 (3)C17—C18—H18A119.6
C8—C9—C4124.2 (3)C14—C19—C18121.0 (3)
C8—C9—H9A117.9C14—C19—H19A119.5
C4—C9—H9A117.9C18—C19—H19A119.5
C8—C10—H10A109.5C16—C20—H20A109.5
C8—C10—H10B109.5C16—C20—H20B109.5
H10A—C10—H10B109.5H20A—C20—H20B109.5
C8—C10—H10C109.5C16—C20—H20C109.5
H10A—C10—H10C109.5H20A—C20—H20C109.5
H10B—C10—H10C109.5H20B—C20—H20C109.5
C3—O1—C2—C1178.1 (3)C13—O3—C12—C11−177.7 (3)
C2—O1—C3—O21.4 (5)C12—O3—C13—O4−2.5 (5)
C2—O1—C3—C4179.7 (3)C12—O3—C13—C14−179.4 (3)
O2—C3—C4—C5−176.4 (3)O4—C13—C14—C19176.4 (4)
O1—C3—C4—C55.4 (5)O3—C13—C14—C19−6.9 (5)
O2—C3—C4—C92.0 (5)O4—C13—C14—C15−0.8 (6)
O1—C3—C4—C9−176.2 (3)O3—C13—C14—C15176.0 (3)
C9—C4—C5—C61.4 (5)C19—C14—C15—C160.8 (5)
C3—C4—C5—C6179.9 (3)C13—C14—C15—C16178.1 (3)
C4—C5—C6—C7−1.9 (6)C14—C15—C16—C17−1.4 (5)
C5—C6—C7—N1179.2 (4)C14—C15—C16—C20−179.6 (3)
C5—C6—C7—C82.7 (6)C15—C16—C17—N2179.5 (4)
N1—C7—C8—C9−179.6 (3)C20—C16—C17—N2−2.3 (6)
C6—C7—C8—C9−3.0 (5)C15—C16—C17—C181.3 (5)
N1—C7—C8—C102.9 (5)C20—C16—C17—C18179.5 (4)
C6—C7—C8—C10179.4 (3)N2—C17—C18—C19−178.9 (4)
C7—C8—C9—C42.8 (5)C16—C17—C18—C19−0.7 (6)
C10—C8—C9—C4−179.7 (3)C15—C14—C19—C18−0.1 (6)
C5—C4—C9—C8−2.0 (5)C13—C14—C19—C18−177.2 (4)
C3—C4—C9—C8179.6 (3)C17—C18—C19—C140.0 (6)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O2i0.862.333.023 (5)138
N1—H1B···N20.862.613.242 (5)131
N2—H2C···O2i0.862.353.160 (4)157
N2—H2D···O4ii0.862.152.967 (4)158
Symmetry codes: (i) x−1, y−1, z; (ii) x, y−1, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O2i0.862.333.023 (5)138
N1—H1B···N20.862.613.242 (5)131
N2—H2C···O2i0.862.353.160 (4)157
N2—H2D···O4ii0.862.152.967 (4)158
Symmetry codes: (i) x−1, y−1, z; (ii) x, y−1, z.
Acknowledgements top

All authors thank Dr Shan Liu for useful discussion.

references
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