PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1802–o1803.
Published online 2009 July 8. doi:  10.1107/S1600536809025379
PMCID: PMC2977149

Ethyl 1-acetyl-1H-indole-3-carboxyl­ate

Abstract

The title compound, C13H13NO3, was synthesized by acetyl­ation of ethyl 1H-indole-3-carboxyl­ate. The aromatic ring system of the mol­ecule is essentially planar, but the saturated ethyl group is also located within this plane and the overall r.m.s. deviation from planarity is only 0.034 Å. Pairs of C—H(...)O inter­actions connect mol­ecules into chains along the diagonal of the unit cell. Mol­ecules also form weakly connected dimers via π(...)π stacking inter­actions of the indole rings with centroid–centroid separations of 3.571 (1) Å. C—H(...)π inter­actions between methyl­ene and methyl groups and the indole and benzene ring complete the directional inter­molecular inter­actions found in the crystal structure.

Related literature

For the biological properties of tryptophan derivatives, see: Ma et al. (2001 [triangle]); Zhou et al. (2006 [triangle]); Zhao, Smith et al. (2002 [triangle]); Zhao, Liao & Cook (2002 [triangle]). For synthetic procedures towards tryptophan-like compounds, see: Ager & Laneman (2004 [triangle]); Amir-Heidari et al. (2007 [triangle]); Carlier et al. (2002 [triangle]); Hengartner et al. (1979 [triangle]); Moriya et al. (1980 [triangle]). For the synthesis of 2-acetamido-3-eth­oxy-3-oxopropanoic acid, see: Hellmann et al. (1958 [triangle]). For NMR data for the title compound, see: Reimann et al. (1990 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1802-scheme1.jpg

Experimental

Crystal data

  • C13H13NO3
  • M r = 231.24
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1802-efi1.jpg
  • a = 7.519 (1) Å
  • b = 8.479 (1) Å
  • c = 10.187 (2) Å
  • α = 97.38 (1)°
  • β = 95.78 (2)°
  • γ = 114.28 (1)°
  • V = 578.58 (15) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 296 K
  • 0.51 × 0.41 × 0.20 mm

Data collection

  • Siemens P4 diffractometer
  • Absorption correction: multi-scan [XSCANS (Siemens, 1996 [triangle]) and XPREP (Siemens, 1994 [triangle])] T min = 0.823, T max = 0.981
  • 2536 measured reflections
  • 2027 independent reflections
  • 1696 reflections with I > 2σ(I)
  • R int = 0.019
  • 3 standard reflections every 97 reflections intensity decay: <1%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.042
  • wR(F 2) = 0.120
  • S = 1.09
  • 2027 reflections
  • 155 parameters
  • H-atom parameters constrained
  • Δρmax = 0.17 e Å−3
  • Δρmin = −0.18 e Å−3

Data collection: XSCANS (Siemens, 1996 [triangle]); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: XPREP (Siemens 1994 [triangle]) and SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809025379/bh2233sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809025379/bh2233Isup2.hkl

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

Acknowledgments

TAS acknowledges the College of Arts and Science at TSU for release time.

supplementary crystallographic information

Comment

Indole substituted at 3-position leads to variety of compounds that are precursors to biologically active important alkaloids. One of the most important compounds of this type is tryptophan, which possesses anticancerous, antimalarial, antiamoebic, and antihypertensive activities (Ma et al., 2001; Zhou et al., 2006; Zhao, Smith et al. 2002; Zhao, Liao, & Cook, 2002). α,β-Dehydroaminoacid esters (e.g.1, Fig. 1) are precursors to synthesizing tryptophan derivatives, which upon hydrogenation yield optically active tryptophan and its analogues (Ager & Laneman, 2004).

α,β-Dehydroamino acid esters were also synthesized using Erlenmeyer condensation (Amir-Heidari et al., 2007), Schmidt olefinations (Carlier et al., 2002), condensation of indole aldehyde with acetylamino malonic acid ester (Hengartner et al., 1979), and Knoevenagel-type condensation (Moriya et al. 1980). One such effort to synthesize hydroxyl dehydrotryptophan (3) from indoleester (1) using mono acid malonic ester (2) and aceticanhydride-pyridine mixture (Fig. 1) proved to be unsuccessful. The reaction resulted in 1H-indole-3-carboxylic acid-N-acetylethyl ester (4) instead. We rationalize that it is the electron withdrawing effect of the ester group which increases the acidity of the molecule. Consequently, in presence of a base, like pyridine, deprotonation and introduction of an acylium ion may occur. In this article we report the crystal structure of this compound.

The structure of the title compound is shown in Figure 2. The aromatic ring system of the molecule is essentially planar, but also the saturated ethyl group is located within this plane and the overall r.m.s. deviation from planarity is only 0.034 Å. Pairs of C—H···O interactions connect molecules into chains along the diagonal of the unit cell (Fig. 3). Molecules form weakly connected dimers viaπ···π stacking interactions of the indole rings with centroid to centroid distances of 3.571 (1) Å [symmetry operator for the second indole ring: (iii) 1 - x, 2 - y, 2 - z]. C—H···π interactions between methylene and methyl groups and the indole and benzene ring complete the range of intermolecular interactions [C12—H12B···Cg1iii = 2.95 Å, X—H···Cg1iii = 127°, X···Cg1iii = 3.618 (3) Å; C13—H13B···Cg2iii = 2.78 Å, X—H···Cg2iii = 142°, X···Cg2iii = 3.587 (3) Å; Cg1 and Cg2 are the centroids of the indole and the benzene rings, respectively].

Experimental

2-Acetamido-3-ethoxy-3-oxopropanoic acid (one of the starting materials) was prepared from acetylamino malonic acid diethylester following the process developed by Hellmann et al. (1958). The title compound was prepared as follows: to a mixture of 0.37 g (1.97 mmol) of the indole ester ethyl 1H-indole-3-carboxylate, 1.1 g (5.9 mmol) of 2-acetamido-3-ethoxy-3-oxopropanoic acid, and 4.54 ml of pyridine was added at 288 K (15 °C) over 15 minutes 1.6 ml of acetic anhydride. The reaction mixture turned yellow and was stirred at 333 K (60 °C) for 3 h. An additional 0.18 g (0.9 mmol) of ethyl acetamido malonate was added and stirring was continued for 22 h. Ice (10 ml) was added, and the mixture was stirred for 2 h and then diluted with 20 ml of water. The resulting solution was extracted with EtOAc (2 × 20 ml), the combined organic layer was dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. 0.4 g (99%) of 1H-indole-3-carboxylicacid-N-acetyl ethyl ester was isolated. 1HNMR CDCl3δ (p.p.m.): 8.70–8.50 (m,1H and 2H), 7.60–7.30 (m, 2H), 4.45 (q, J = 7 Hz, OCH2CH3), 2.70 (s, COCH3), 1.45 (t, J = 7 Hz, OCH2CH3). The NMR data agree with those reported previously (Reimann et al., 1990). Crystals suitable for X-ray structural analysis were obtained by recrystallization form ethanol in a refrigerator.

Refinement

All hydrogen atoms were added in calculated positions with a C—H bond distances of 0.97 (methylene), 0.93 (aromatic) and 0.96 Å (methyl). They were refined with isotropic displacement parameters Uiso of 1.5 (methyl) or 1.2 times Ueq (all others) of the adjacent carbon atom.

Figures

Fig. 1.
Synthesis of the title compound (4).
Fig. 2.
Thermal ellipsoid plot of the title compound with the atom labeling scheme. Displacement ellipsoids are shown at the 50% probability level and H atoms are shown as capped sticks.
Fig. 3.
Packing view of the title compound showing C—H···O interactions (blue lines).

Crystal data

C13H13NO3Z = 2
Mr = 231.24F(000) = 244
Triclinic, P1Dx = 1.327 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.519 (1) ÅCell parameters from 23 reflections
b = 8.479 (1) Åθ = 3.7–11.4°
c = 10.187 (2) ŵ = 0.10 mm1
α = 97.38 (1)°T = 296 K
β = 95.78 (2)°Block, colourless
γ = 114.28 (1)°0.51 × 0.41 × 0.20 mm
V = 578.58 (15) Å3

Data collection

Siemens P4 diffractometer1696 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.019
graphiteθmax = 25.0°, θmin = 2.1°
2θ/ω scansh = −8→1
Absorption correction: multi-scan [XSCANS (Siemens 1996) and XPREP (Siemens, 1994)]k = −9→9
Tmin = 0.823, Tmax = 0.981l = −12→12
2536 measured reflections3 standard reflections every 97 reflections
2027 independent reflections intensity decay: <1%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.120w = 1/[σ2(Fo2) + (0.0647P)2 + 0.0738P] where P = (Fo2 + 2Fc2)/3
S = 1.09(Δ/σ)max = 0.001
2027 reflectionsΔρmax = 0.17 e Å3
155 parametersΔρmin = −0.18 e Å3
0 restraintsExtinction correction: SHELXTL (Bruker, 2003; Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 constraintsExtinction coefficient: 0.103 (12)
Primary atom site location: structure-invariant direct methods

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
C10.3179 (2)0.9158 (2)0.76860 (15)0.0474 (4)
C20.3276 (2)0.8319 (2)0.64495 (16)0.0560 (4)
H20.39260.89520.58260.067*
C30.2364 (3)0.6502 (2)0.61896 (18)0.0641 (5)
H30.24020.58980.53710.077*
C40.1394 (3)0.5554 (2)0.71141 (19)0.0658 (5)
H40.08040.43300.69070.079*
C50.1286 (3)0.6392 (2)0.83389 (17)0.0572 (4)
H50.06290.57470.89550.069*
C60.2186 (2)0.8227 (2)0.86285 (15)0.0477 (4)
C70.2359 (2)0.9517 (2)0.97738 (15)0.0477 (4)
C80.3421 (2)1.1130 (2)0.95024 (15)0.0491 (4)
H80.37471.21891.00770.059*
C90.1539 (2)0.9133 (2)1.10037 (16)0.0526 (4)
C100.5038 (3)1.2371 (2)0.76197 (16)0.0563 (4)
C110.5648 (3)1.4194 (3)0.8383 (2)0.0756 (6)
H11A0.63921.43360.92480.113*
H11B0.44911.43770.84970.113*
H11C0.64521.50370.78940.113*
C120.1351 (3)1.0333 (3)1.31867 (17)0.0613 (5)
H12A0.19500.96831.36340.074*
H12B−0.00760.96671.30450.074*
C130.1950 (3)1.2107 (3)1.40273 (18)0.0724 (5)
H13A0.15081.19701.48750.109*
H13B0.13611.27431.35720.109*
H13C0.33661.27471.41750.109*
N10.39555 (19)1.09788 (17)0.82406 (12)0.0489 (4)
O10.0559 (3)0.76795 (18)1.11828 (14)0.0845 (5)
O20.20161 (17)1.05915 (15)1.19112 (11)0.0559 (3)
O30.5434 (2)1.20764 (19)0.65295 (13)0.0814 (5)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0485 (8)0.0506 (9)0.0420 (8)0.0226 (7)0.0046 (6)0.0028 (6)
C20.0594 (10)0.0612 (10)0.0452 (9)0.0262 (8)0.0100 (7)0.0006 (7)
C30.0707 (11)0.0617 (11)0.0531 (10)0.0282 (9)0.0083 (8)−0.0092 (8)
C40.0744 (11)0.0493 (10)0.0660 (11)0.0245 (9)0.0072 (9)−0.0049 (8)
C50.0631 (10)0.0494 (9)0.0552 (10)0.0216 (8)0.0084 (8)0.0070 (7)
C60.0492 (8)0.0497 (8)0.0437 (8)0.0231 (7)0.0043 (6)0.0036 (7)
C70.0521 (8)0.0502 (9)0.0419 (8)0.0239 (7)0.0077 (6)0.0062 (7)
C80.0569 (9)0.0503 (9)0.0405 (8)0.0245 (7)0.0102 (6)0.0032 (6)
C90.0617 (9)0.0541 (10)0.0467 (9)0.0283 (8)0.0122 (7)0.0108 (7)
C100.0656 (10)0.0570 (10)0.0478 (9)0.0254 (8)0.0155 (7)0.0131 (7)
C110.0980 (15)0.0525 (11)0.0726 (12)0.0247 (10)0.0284 (11)0.0146 (9)
C120.0718 (11)0.0789 (12)0.0442 (9)0.0395 (10)0.0208 (8)0.0160 (8)
C130.0812 (13)0.0925 (14)0.0491 (10)0.0451 (11)0.0156 (9)0.0023 (9)
N10.0562 (8)0.0484 (7)0.0406 (7)0.0215 (6)0.0105 (5)0.0044 (5)
O10.1286 (12)0.0546 (8)0.0692 (9)0.0304 (8)0.0424 (8)0.0197 (6)
O20.0660 (7)0.0586 (7)0.0430 (6)0.0256 (6)0.0172 (5)0.0069 (5)
O30.1158 (11)0.0731 (9)0.0556 (8)0.0346 (8)0.0377 (7)0.0162 (7)

Geometric parameters (Å, °)

C1—C21.389 (2)C9—O11.197 (2)
C1—C61.399 (2)C9—O21.3367 (19)
C1—N11.4186 (19)C10—O31.201 (2)
C2—C31.379 (2)C10—N11.400 (2)
C2—H20.9300C10—C111.497 (3)
C3—C41.384 (3)C11—H11A0.9600
C3—H30.9300C11—H11B0.9600
C4—C51.381 (2)C11—H11C0.9600
C4—H40.9300C12—O21.449 (2)
C5—C61.393 (2)C12—C131.494 (3)
C5—H50.9300C12—H12A0.9700
C6—C71.449 (2)C12—H12B0.9700
C7—C81.352 (2)C13—H13A0.9600
C7—C91.467 (2)C13—H13B0.9600
C8—N11.391 (2)C13—H13C0.9600
C8—H80.9300
C2—C1—C6122.32 (15)O2—C9—C7112.43 (14)
C2—C1—N1130.20 (15)O3—C10—N1120.26 (16)
C6—C1—N1107.48 (13)O3—C10—C11123.11 (16)
C3—C2—C1116.89 (17)N1—C10—C11116.63 (15)
C3—C2—H2121.6C10—C11—H11A109.5
C1—C2—H2121.6C10—C11—H11B109.5
C2—C3—C4121.75 (17)H11A—C11—H11B109.5
C2—C3—H3119.1C10—C11—H11C109.5
C4—C3—H3119.1H11A—C11—H11C109.5
C5—C4—C3121.27 (17)H11B—C11—H11C109.5
C5—C4—H4119.4O2—C12—C13107.88 (15)
C3—C4—H4119.4O2—C12—H12A110.1
C4—C5—C6118.33 (17)C13—C12—H12A110.1
C4—C5—H5120.8O2—C12—H12B110.1
C6—C5—H5120.8C13—C12—H12B110.1
C5—C6—C1119.44 (14)H12A—C12—H12B108.4
C5—C6—C7133.47 (15)C12—C13—H13A109.5
C1—C6—C7107.10 (14)C12—C13—H13B109.5
C8—C7—C6107.50 (14)H13A—C13—H13B109.5
C8—C7—C9126.52 (15)C12—C13—H13C109.5
C6—C7—C9125.98 (15)H13A—C13—H13C109.5
C7—C8—N1110.33 (14)H13B—C13—H13C109.5
C7—C8—H8124.8C8—N1—C10126.27 (14)
N1—C8—H8124.8C8—N1—C1107.60 (13)
O1—C9—O2123.51 (15)C10—N1—C1126.12 (13)
O1—C9—C7124.06 (16)C9—O2—C12116.25 (13)
C6—C1—C2—C3−0.9 (2)C8—C7—C9—O1177.82 (17)
N1—C1—C2—C3−179.95 (15)C6—C7—C9—O1−2.6 (3)
C1—C2—C3—C40.1 (3)C8—C7—C9—O2−2.5 (2)
C2—C3—C4—C50.5 (3)C6—C7—C9—O2177.09 (13)
C3—C4—C5—C6−0.2 (3)C7—C8—N1—C10179.14 (15)
C4—C5—C6—C1−0.6 (2)C7—C8—N1—C10.04 (17)
C4—C5—C6—C7179.54 (17)O3—C10—N1—C8179.02 (16)
C2—C1—C6—C51.2 (2)C11—C10—N1—C8−1.0 (3)
N1—C1—C6—C5−179.57 (13)O3—C10—N1—C1−2.1 (3)
C2—C1—C6—C7−178.95 (14)C11—C10—N1—C1177.96 (15)
N1—C1—C6—C70.31 (16)C2—C1—N1—C8178.95 (16)
C5—C6—C7—C8179.58 (17)C6—C1—N1—C8−0.23 (16)
C1—C6—C7—C8−0.29 (17)C2—C1—N1—C10−0.1 (3)
C5—C6—C7—C90.0 (3)C6—C1—N1—C10−179.32 (15)
C1—C6—C7—C9−179.90 (14)O1—C9—O2—C122.7 (2)
C6—C7—C8—N10.15 (18)C7—C9—O2—C12−177.03 (13)
C9—C7—C8—N1179.76 (14)C13—C12—O2—C9−177.54 (14)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C2—H2···O3i0.932.613.296 (2)131
C5—H5···O1ii0.932.643.273 (2)125
C12—H12B···Cg1iii0.962.953.618 (3)127
C13—H13B···Cg2iii0.962.783.587 (3)142

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BH2233).

References

  • Ager, D. J. & Laneman, S. (2004). Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions, edited by H. U. Blaser & E. Schmidt, p. 30. Weinheim: WILEY-VCH Verlag GmbH & Co KGaA.
  • Amir-Heidari, B., Thirlway, J. & Micklefield, J. (2007). Org. Lett.9, 1513–1516. [PubMed]
  • Carlier, P. R., Lam, P. C.-H. & Wong, D. M. (2002). J. Org. Chem.67, 6256–6259. [PubMed]
  • Hellmann, H., Teichmann, K. & Lingens, F. (1958). Chem. Ber.91, 2427–2431.
  • Hengartner, U., Valentine, D. Jr, Johnson, K. K., Larscheid, M. E., Pigott, F., Scheidl, F., Scott, J. W., Sun, R. C., Townsend, J. M. & Williams, T. H. (1979). J. Org. Chem.44, 3741–3747.
  • Ma, C., Liu, X., Li, X., Flippen-Anderson, J., Yu, S. & Cook, J. M. (2001). J. Org. Chem.66, 4525–4542. [PubMed]
  • Moriya, T., Hagio, K. & Yoneda, N. (1980). Chem. Pharm. Bull.28, 1711–1721.
  • Reimann, E., Hassler, T. & Lotter, H. (1990). Arch. Pharm.323, 255–258.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Siemens (1994). XPREP Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.
  • Siemens (1996). XSCANS Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.
  • Zhao, S., Liao, X. & Cook, J. M. (2002). Org. Lett.4, 687–690. [PubMed]
  • Zhao, S., Smith, K. S., Deveau, A. M., Dieckhaus, C. M., Johnson, M. A., Macdonald, T. L. & Cook, J. M. (2002). J. Med. Chem.45, 1559–1562. [PubMed]
  • Zhou, H., Liao, X., Yin, W., Ma, J. & Cook, J. M. (2006). J. Org. Chem.71, 251–259. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography