Acta Cryst. (2008). E64, o742 [ doi:10.1107/S1600536808005576 ]
The title compound, C13H16N2O5, is useful as an intermediate in the field of agrochemicals. Intramolecular C-H
O hydrogen bonds result in the formation of one six- and one five-membered nearly planar ring; the six-membered ring is also nearly coplanar with the adjacent benzene ring. In the crystal structure, intermolecular C-HO hydrogen bonds link the molecules.
For the preparation of the title compound, methyl 4-amino-3-methylbenzoate (8.25 g, 50 mmol) was acylated with butyryl chloride (50 mmol, 5.3 ml) in chlorobenzene at 373 K. The resulting amide was reacted with fuming nitric acid in sulfuric acid (60%) at 273 K. The reaction mixture was poured into ice-water. The residue was filtered and recrystallized from methylene chloride to give the title compound, (I), (yield; 10.8 g, 77%). Crystals suitable for X-ray analysis were obtained by slow evaporation of an ethanol solution.
H 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.
Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: X-CAD4 (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).
![[Figure 1]](./hk2408fig1thm.gif)
| 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]](./hk2408fig2thm.gif)
| Fig. 2. A packing diagram of (I). Hydrogen bonds are shown as dashed lines. |
| C13H16N2O5 | Z = 2 |
| Mr = 280.28 | F000 = 296 |
| Triclinic, P1 | Dx = 1.349 Mg m−3 |
| Hall symbol: -P 1 | Mo Kα radiation λ = 0.71073 Å |
| a = 7.6370 (15) Å | Cell parameters from 25 reflections |
| b = 8.7880 (18) Å | θ = 9–14º |
| c = 11.329 (2) Å | µ = 0.11 mm−1 |
| α = 81.06 (3)º | T = 294 (2) K |
| β = 78.48 (3)º | Block, colorless |
| γ = 68.39 (3)º | 0.30 × 0.20 × 0.10 mm |
| V = 689.9 (3) Å3 |
| Enraf–Nonius CAD-4 diffractometer | Rint = 0.032 |
| Radiation source: fine-focus sealed tube | θmax = 26.0º |
| Monochromator: graphite | θmin = 1.8º |
| T = 294(2) K | h = −9→9 |
| ω/2θ scans | k = −10→10 |
| Absorption correction: ψ scan (North et al., 1968) | l = 0→13 |
| Tmin = 0.959, Tmax = 0.980 | 3 standard reflections |
| 2919 measured reflections | every 120 min |
| 2704 independent reflections | intensity decay: none |
| 1650 reflections with I > 2σ(I) |
| Refinement on F2 | Secondary atom site location: difference Fourier map |
| Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
| R[F2 > 2σ(F2)] = 0.056 | H-atom parameters constrained |
| wR(F2) = 0.161 | w = 1/[σ2(Fo2) + (0.06P)2 + 0.4P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.01 | (Δ/σ)max < 0.001 |
| 2704 reflections | Δρmax = 0.20 e Å−3 |
| 181 parameters | Δρmin = −0.18 e Å−3 |
| Primary atom site location: structure-invariant direct methods | Extinction correction: none |
| C13H16N2O5 | γ = 68.39 (3)º |
| Mr = 280.28 | V = 689.9 (3) Å3 |
| Triclinic, P1 | Z = 2 |
| a = 7.6370 (15) Å | Mo Kα |
| b = 8.7880 (18) Å | µ = 0.11 mm−1 |
| c = 11.329 (2) Å | T = 294 (2) K |
| α = 81.06 (3)º | 0.30 × 0.20 × 0.10 mm |
| β = 78.48 (3)º |
| Enraf–Nonius CAD-4 diffractometer | 1650 reflections with I > 2σ(I) |
| Absorption correction: ψ scan (North et al., 1968) | Rint = 0.032 |
| Tmin = 0.959, Tmax = 0.980 | 3 standard reflections |
| 2919 measured reflections | every 120 min |
| 2704 independent reflections | intensity decay: none |
| R[F2 > 2σ(F2)] = 0.056 | 181 parameters |
| wR(F2) = 0.161 | H-atom parameters constrained |
| S = 1.01 | Δρmax = 0.20 e Å−3 |
| 2704 reflections | Δρmin = −0.18 e Å−3 |
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. |
| x | y | z | Uiso*/Ueq | ||
| N1 | 0.2769 (4) | −0.1219 (3) | −0.0125 (2) | 0.0492 (6) | |
| H1A | 0.3013 | −0.2242 | 0.0119 | 0.059* | |
| O1 | 0.2083 (4) | 0.0590 (3) | −0.1748 (2) | 0.0845 (9) | |
| C1 | 0.2766 (5) | −0.3253 (4) | −0.3938 (3) | 0.0681 (10) | |
| H1B | 0.2607 | −0.2909 | −0.4769 | 0.102* | |
| H1C | 0.1823 | −0.3727 | −0.3551 | 0.102* | |
| H1D | 0.4016 | −0.4056 | −0.3901 | 0.102* | |
| N2 | 0.1750 (4) | 0.4161 (3) | 0.1056 (2) | 0.0454 (6) | |
| O2 | 0.0124 (3) | 0.5069 (2) | 0.1365 (2) | 0.0693 (7) | |
| C2 | 0.2531 (5) | −0.1773 (4) | −0.3296 (3) | 0.0520 (8) | |
| H2A | 0.3459 | −0.1278 | −0.3706 | 0.062* | |
| H2B | 0.1270 | −0.0962 | −0.3341 | 0.062* | |
| O3 | 0.3005 (3) | 0.4618 (3) | 0.0453 (2) | 0.0634 (7) | |
| C3 | 0.2792 (4) | −0.2244 (3) | −0.1980 (2) | 0.0454 (7) | |
| H3A | 0.1893 | −0.2776 | −0.1582 | 0.054* | |
| H3B | 0.4066 | −0.3034 | −0.1941 | 0.054* | |
| O4 | 0.2265 (3) | 0.1922 (2) | 0.46212 (17) | 0.0595 (6) | |
| C4 | 0.2510 (4) | −0.0805 (3) | −0.1302 (2) | 0.0445 (7) | |
| O5 | 0.2355 (3) | 0.4105 (2) | 0.33631 (17) | 0.0585 (6) | |
| C5 | 0.2695 (4) | −0.0219 (3) | 0.0744 (2) | 0.0397 (6) | |
| C6 | 0.2311 (4) | 0.1466 (3) | 0.0483 (2) | 0.0383 (6) | |
| H6A | 0.2122 | 0.1962 | −0.0291 | 0.046* | |
| C7 | 0.2217 (4) | 0.2382 (3) | 0.1391 (2) | 0.0356 (6) | |
| C8 | 0.2483 (4) | 0.1712 (3) | 0.2565 (2) | 0.0394 (6) | |
| C9 | 0.2896 (4) | 0.0022 (3) | 0.2777 (2) | 0.0461 (7) | |
| H9A | 0.3106 | −0.0474 | 0.3548 | 0.055* | |
| C10 | 0.3010 (4) | −0.0948 (3) | 0.1907 (2) | 0.0456 (7) | |
| C11 | 0.3466 (7) | −0.2777 (4) | 0.2205 (3) | 0.0822 (13) | |
| H11A | 0.3653 | −0.3065 | 0.3035 | 0.123* | |
| H11B | 0.4607 | −0.3358 | 0.1691 | 0.123* | |
| H11C | 0.2428 | −0.3069 | 0.2079 | 0.123* | |
| C12 | 0.2353 (4) | 0.2736 (3) | 0.3534 (2) | 0.0402 (6) | |
| C13 | 0.2136 (6) | 0.2797 (4) | 0.5634 (3) | 0.0723 (11) | |
| H13A | 0.2095 | 0.2093 | 0.6370 | 0.108* | |
| H13B | 0.0999 | 0.3754 | 0.5674 | 0.108* | |
| H13C | 0.3230 | 0.3125 | 0.5531 | 0.108* |
| U11 | U22 | U33 | U12 | U13 | U23 | |
| N1 | 0.0804 (19) | 0.0346 (12) | 0.0354 (12) | −0.0212 (12) | −0.0131 (12) | −0.0035 (9) |
| O1 | 0.165 (3) | 0.0436 (13) | 0.0494 (13) | −0.0360 (15) | −0.0326 (15) | 0.0018 (10) |
| C1 | 0.090 (3) | 0.072 (2) | 0.0495 (19) | −0.032 (2) | −0.0078 (18) | −0.0197 (16) |
| N2 | 0.0652 (17) | 0.0380 (13) | 0.0380 (13) | −0.0210 (13) | −0.0154 (12) | −0.0009 (10) |
| O2 | 0.0695 (16) | 0.0383 (12) | 0.0819 (17) | 0.0019 (11) | −0.0134 (13) | −0.0029 (11) |
| C2 | 0.059 (2) | 0.0473 (16) | 0.0487 (17) | −0.0144 (14) | −0.0101 (15) | −0.0114 (13) |
| O3 | 0.0922 (18) | 0.0483 (12) | 0.0568 (13) | −0.0405 (12) | −0.0019 (12) | 0.0022 (10) |
| C3 | 0.0543 (18) | 0.0422 (15) | 0.0443 (16) | −0.0216 (13) | −0.0042 (13) | −0.0099 (12) |
| O4 | 0.1073 (18) | 0.0430 (11) | 0.0345 (11) | −0.0323 (11) | −0.0149 (11) | −0.0013 (9) |
| C4 | 0.0537 (18) | 0.0375 (15) | 0.0423 (16) | −0.0169 (13) | −0.0060 (13) | −0.0029 (12) |
| O5 | 0.1011 (18) | 0.0393 (11) | 0.0447 (12) | −0.0343 (11) | −0.0136 (11) | −0.0036 (9) |
| C5 | 0.0521 (17) | 0.0328 (13) | 0.0365 (14) | −0.0161 (12) | −0.0063 (12) | −0.0072 (11) |
| C6 | 0.0496 (17) | 0.0333 (13) | 0.0312 (13) | −0.0133 (12) | −0.0063 (12) | −0.0035 (10) |
| C7 | 0.0435 (16) | 0.0272 (12) | 0.0377 (14) | −0.0140 (11) | −0.0081 (12) | −0.0007 (10) |
| C8 | 0.0469 (17) | 0.0336 (13) | 0.0402 (15) | −0.0168 (12) | −0.0065 (12) | −0.0036 (11) |
| C9 | 0.071 (2) | 0.0356 (14) | 0.0319 (14) | −0.0193 (14) | −0.0096 (13) | 0.0002 (11) |
| C10 | 0.070 (2) | 0.0306 (13) | 0.0362 (14) | −0.0193 (13) | −0.0060 (13) | −0.0003 (11) |
| C11 | 0.164 (4) | 0.0358 (16) | 0.0499 (19) | −0.035 (2) | −0.026 (2) | 0.0017 (14) |
| C12 | 0.0459 (17) | 0.0356 (14) | 0.0384 (15) | −0.0138 (12) | −0.0063 (12) | −0.0028 (11) |
| C13 | 0.129 (3) | 0.0519 (19) | 0.0386 (18) | −0.032 (2) | −0.0169 (19) | −0.0070 (14) |
| N1—C4 | 1.361 (3) | O4—C13 | 1.446 (3) |
| N1—C5 | 1.398 (3) | O5—C12 | 1.190 (3) |
| N1—H1A | 0.8600 | C5—C6 | 1.394 (3) |
| O1—C4 | 1.202 (3) | C5—C10 | 1.399 (4) |
| C1—C2 | 1.524 (4) | C6—C7 | 1.377 (3) |
| C1—H1B | 0.9600 | C6—H6A | 0.9300 |
| C1—H1C | 0.9600 | C7—C8 | 1.391 (3) |
| C1—H1D | 0.9600 | C8—C9 | 1.391 (4) |
| N2—O3 | 1.218 (3) | C8—C12 | 1.490 (4) |
| N2—O2 | 1.218 (3) | C9—C10 | 1.370 (4) |
| N2—C7 | 1.474 (3) | C9—H9A | 0.9300 |
| C2—C3 | 1.516 (4) | C10—C11 | 1.512 (4) |
| C2—H2A | 0.9700 | C11—H11A | 0.9600 |
| C2—H2B | 0.9700 | C11—H11B | 0.9600 |
| C3—C4 | 1.507 (4) | C11—H11C | 0.9600 |
| C3—H3A | 0.9700 | C13—H13A | 0.9600 |
| C3—H3B | 0.9700 | C13—H13B | 0.9600 |
| O4—C12 | 1.327 (3) | C13—H13C | 0.9600 |
| C4—N1—C5 | 129.3 (2) | C7—C6—C5 | 118.9 (2) |
| C4—N1—H1A | 115.4 | C7—C6—H6A | 120.6 |
| C5—N1—H1A | 115.4 | C5—C6—H6A | 120.6 |
| C2—C1—H1B | 109.5 | C6—C7—C8 | 123.3 (2) |
| C2—C1—H1C | 109.5 | C6—C7—N2 | 115.7 (2) |
| H1B—C1—H1C | 109.5 | C8—C7—N2 | 121.0 (2) |
| C2—C1—H1D | 109.5 | C7—C8—C9 | 115.8 (2) |
| H1B—C1—H1D | 109.5 | C7—C8—C12 | 122.1 (2) |
| H1C—C1—H1D | 109.5 | C9—C8—C12 | 122.1 (2) |
| O3—N2—O2 | 124.3 (2) | C10—C9—C8 | 123.4 (3) |
| O3—N2—C7 | 117.5 (2) | C10—C9—H9A | 118.3 |
| O2—N2—C7 | 118.1 (2) | C8—C9—H9A | 118.3 |
| C3—C2—C1 | 112.0 (3) | C9—C10—C5 | 119.0 (2) |
| C3—C2—H2A | 109.2 | C9—C10—C11 | 120.3 (2) |
| C1—C2—H2A | 109.2 | C5—C10—C11 | 120.7 (2) |
| C3—C2—H2B | 109.2 | C10—C11—H11A | 109.5 |
| C1—C2—H2B | 109.2 | C10—C11—H11B | 109.5 |
| H2A—C2—H2B | 107.9 | H11A—C11—H11B | 109.5 |
| C4—C3—C2 | 113.6 (2) | C10—C11—H11C | 109.5 |
| C4—C3—H3A | 108.8 | H11A—C11—H11C | 109.5 |
| C2—C3—H3A | 108.8 | H11B—C11—H11C | 109.5 |
| C4—C3—H3B | 108.8 | O5—C12—O4 | 123.6 (2) |
| C2—C3—H3B | 108.8 | O5—C12—C8 | 124.7 (2) |
| H3A—C3—H3B | 107.7 | O4—C12—C8 | 111.7 (2) |
| C12—O4—C13 | 116.5 (2) | O4—C13—H13A | 109.5 |
| O1—C4—N1 | 122.4 (3) | O4—C13—H13B | 109.5 |
| O1—C4—C3 | 123.6 (3) | H13A—C13—H13B | 109.5 |
| N1—C4—C3 | 114.0 (2) | O4—C13—H13C | 109.5 |
| C6—C5—N1 | 122.0 (2) | H13A—C13—H13C | 109.5 |
| C6—C5—C10 | 119.7 (2) | H13B—C13—H13C | 109.5 |
| N1—C5—C10 | 118.3 (2) | ||
| C1—C2—C3—C4 | −178.2 (3) | C6—C7—C8—C12 | −179.3 (3) |
| C5—N1—C4—O1 | −3.1 (5) | N2—C7—C8—C12 | −1.3 (4) |
| C5—N1—C4—C3 | 177.3 (3) | C7—C8—C9—C10 | −1.1 (4) |
| C2—C3—C4—O1 | 1.4 (4) | C12—C8—C9—C10 | 179.5 (3) |
| C2—C3—C4—N1 | −179.1 (3) | C8—C9—C10—C5 | −0.1 (5) |
| C4—N1—C5—C6 | 0.1 (5) | C8—C9—C10—C11 | 180.0 (3) |
| C4—N1—C5—C10 | 179.8 (3) | C6—C5—C10—C9 | 1.3 (4) |
| N1—C5—C6—C7 | 178.5 (3) | N1—C5—C10—C9 | −178.4 (3) |
| C10—C5—C6—C7 | −1.2 (4) | C6—C5—C10—C11 | −178.8 (3) |
| C5—C6—C7—C8 | −0.1 (4) | N1—C5—C10—C11 | 1.5 (4) |
| C5—C6—C7—N2 | −178.3 (2) | C13—O4—C12—O5 | 1.0 (4) |
| O3—N2—C7—C6 | −75.9 (3) | C13—O4—C12—C8 | 179.9 (3) |
| O2—N2—C7—C6 | 101.7 (3) | C7—C8—C12—O5 | −13.9 (4) |
| O3—N2—C7—C8 | 105.9 (3) | C9—C8—C12—O5 | 165.5 (3) |
| O2—N2—C7—C8 | −76.5 (3) | C7—C8—C12—O4 | 167.1 (3) |
| C6—C7—C8—C9 | 1.2 (4) | C9—C8—C12—O4 | −13.5 (4) |
| N2—C7—C8—C9 | 179.3 (3) |
| D—H···A | D—H | H···A | D···A | D—H···A |
| C6—H6A···O1 | 0.93 | 2.20 | 2.809 (3) | 122 |
| C9—H9A···O4 | 0.93 | 2.41 | 2.734 (3) | 100 |
| C13—H13A···O1i | 0.96 | 2.33 | 3.284 (4) | 174 |
| Symmetry codes: (i) x, y, z+1. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| C6—H6A···O1 | 0.93 | 2.20 | 2.809 (3) | 122 |
| C9—H9A···O4 | 0.93 | 2.41 | 2.734 (3) | 100 |
| C13—H13A···O1i | 0.96 | 2.33 | 3.284 (4) | 174 |
| Symmetry codes: (i) x, y, z+1. |
The authors thank the Center of Testing and Analysis, Nanjing University, for the support.
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
Boustany, C. M., Bharadwaj, K., Daugherty, A., Brown, D. R., Randall, D. C. & Cassis, L. A. (2004). Am. J. Physiol. Regul. Integr. Comp. Physiol. 287, R943–R949.
Engeli, S., Negrel, R. & Sharma, A. M. (2000). Hypertension, 35, 1270–1277.
Enraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.
Goossens, G. H., Blaak, E. E. & van Baak, M. A. (2003). Obes. Rev. 4, 43–55.
Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.
Kintscher, U., Lyon, C. J. & Law, R. E. (2004). Front. Biosci. 9, 359–369.
North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
Ries, U. J., Mihm, G., Narr, B., Hasselbach, K. M., Wittneben, H., Entzeroth, M., van Meel, J. C. A., Wolfgang Wienen, W. & Hauel, N. H. (1993). J. Med. Chem. 36, 4040–4051.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
The title compound, (I), is useful as an intermediate and agrochemicals. It is important as an intermediate for the preparation of telmisartan (Ries et al., 1993), that 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; Boustany et al., 2004). As part of our ongoing studies in this area, we report herein the synthesis and crystal structure of the title compound, (I).
In the molecule of (I) (Fig. 1), the ligand bond lengths and angles are within normal ranges (Allen et al., 1987). The intramolecular C—H···O hydrogen bonds (Table 1) result in the formations of one six- and one five-membered nearly planar rings; B (N1/O1/C4—C6/H6A) and C (O4/C8/C9/C12/H9A). Ring A (C5—C10) is, of course, planar and the dihedral angles between them are A/B = 2.01 (3)°, A/C = 6.76 (3)° and B/C = 8.73 (2)°. So, rings A and B are also nearly co-planar.
In the crystal structure, intermolecular C—H···O hydrogen bonds (Table 1) link the molecules (Fig. 2), in which they seem to be effective in the stabilization of the structure.