organic compounds
Ethyl 1H-indole-2-carboxylate
aGeorgia Southern University, Department of Chemistry and Biochemistry, Box 8064, Statesboro, GA 30460, USA
*Correspondence e-mail: wlynch@georgiasouthern.edu
Our work in the area of synthesis of tris indole compounds as a potential chelator led to the synthesis and crystallization of ethyl 1H-indole-2-carboxylate, C11H11NO2, an indole that was synthesized by the thionyl chloride reaction of 1H-indole-2-carboxylic acid, followed by dissolution in ethanol. The molecular packing exhibits a herringbone pattern with the zigzag running along the b-axis direction; the compound crystallizes as a hydrogen-bonded dimer resulting from O⋯H—N hydrogen bonds, between the indole N—H group and the keto oxygen atom, which build centrosymmetric R22(10) ring motifs in the crystal.
Keywords: crystal structure; indole; hydrogen bonding.
CCDC reference: 2026531
Structure description
Indole H-indole-2-carboxylic acid via an isolated acyl chloride intermediate followed by dissolving the residue in the appropriate alcohol solvent. These indole-type compounds are of interest because of their prevalence in nature (Stempel & Gaich, 2016). Derivatives of this type of compound have also been implicated in a number of biological roles including antifungal (Kipp et al., 1999), antitumor (Lu et al., 2016) and anti-inflammatory (Liu et al., 2016) agents. These types of compounds have also been reported as potential cellular inhibitors of kinase (Jobson et al., 2009) as well as an antagonist for glycine-binding sites (Ohtani et al., 2002). Previous reports include the structures of indole-2-carboxylic acid (Morzyk-Ociepa et al., 2004) and methyl 1H-indole-2-carboxylate (Almutairi et al., 2017).
can easily be prepared from 1Herein we report the H-indole-2-carboxylate (Fig. 1), which forms a hydrogen-bonded dimer. The hydrogen bonding occurs between N atoms of the indole ring and the keto oxygen atoms with an R(10) synthon. The hydrogen bond between N1 and O2i is characterized by an N⋯O separation of 2.877 (3) Å [symmetry code: (i) −x + 2, −y + 1, −z + 1; Table 1], and the ring motifs, R22(10), are placed on inversion centres in the P21/c (Fig. 2). The exhibits a classic herringbone pattern (Fig. 2) with the blocks consisting of the hydrogen-bonded dimers, with the zigzag running along the b-axis direction. The molecule is nearly planar, with a r.m.s.d. of 0.028 Å for the non-hydrogen atoms. There are no other short contacts or π–π interactions observed in the crystal.
of ethyl 1Synthesis and crystallization
The title compound was synthesized by modification of an early method laid out by Terent'ev et al. (1969). Indole-2-carboxylic acid (0.50 g, 3.1 mmol) was dissolved in SOCl2 (19 ml) at 0°C. After stirring for 1 h, the solution was rotary evaporated and to the resulting oil was added absolute ethanol (17 ml) at room temperature. After stirring overnight, the solution was vacuum filtered to yield ethyl 1H-indole-2-carboxylate as a beige solid, which was recrystallized from methanol to yield 0.54 g (2.9 mmol, 93%) of the product. Further recrystallization by slow evaporation from methanol solution resulted in X-ray quality crystals.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 2026531
https://doi.org/10.1107/S2414314620012055/bh4054sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314620012055/bh4054Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314620012055/bh4054Isup3.cml
Data collection: CrysAlis PRO (Rigaku OD, 2018); cell
CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: ShelXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C11H11NO2 | F(000) = 400 |
Mr = 189.21 | Dx = 1.280 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 5.5622 (7) Å | Cell parameters from 611 reflections |
b = 18.891 (2) Å | θ = 2.4–21.1° |
c = 9.6524 (13) Å | µ = 0.09 mm−1 |
β = 104.454 (13)° | T = 170 K |
V = 982.1 (2) Å3 | Needle, colourless |
Z = 4 | 0.4 × 0.05 × 0.05 mm |
Rigaku XtaLAB mini diffractometer | 1804 independent reflections |
Radiation source: fine-focus sealed X-ray tube, Rigaku (Mo) X-ray Source | 991 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.047 |
ω scans | θmax = 25.3°, θmin = 2.2° |
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2018) | h = −6→6 |
Tmin = 0.998, Tmax = 1.000 | k = −22→22 |
5586 measured reflections | l = −6→11 |
Refinement on F2 | Primary atom site location: dual |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.049 | Hydrogen site location: mixed |
wR(F2) = 0.144 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.01 | w = 1/[σ2(Fo2) + (0.0611P)2] where P = (Fo2 + 2Fc2)/3 |
1804 reflections | (Δ/σ)max < 0.001 |
132 parameters | Δρmax = 0.28 e Å−3 |
0 restraints | Δρmin = −0.16 e Å−3 |
Refinement. All carbon-bound H atoms were positioned geometrically and refined as riding, with C—H = 0.95, 0.98 or 0.99 Å and Uiso(H) = 1.2Ueq(C) or Uiso(H) = 1.5Ueq(C) for C(H) and CH3 groups, respectively. Hydrogen atom of the N—H group was refined freely. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.4202 (3) | 0.51968 (8) | 0.18977 (19) | 0.0674 (5) | |
O2 | 0.8074 (3) | 0.53509 (10) | 0.32447 (19) | 0.0769 (6) | |
N1 | 0.7445 (4) | 0.41313 (12) | 0.4844 (2) | 0.0618 (6) | |
C1 | 0.6528 (4) | 0.35476 (13) | 0.5376 (2) | 0.0546 (6) | |
C6 | 0.4072 (4) | 0.34466 (13) | 0.4568 (2) | 0.0561 (6) | |
C9 | 0.6121 (5) | 0.50269 (13) | 0.2963 (3) | 0.0603 (7) | |
C8 | 0.5633 (4) | 0.44041 (13) | 0.3735 (3) | 0.0559 (6) | |
C7 | 0.3542 (4) | 0.39987 (13) | 0.3545 (3) | 0.0604 (7) | |
H7 | 0.201542 | 0.407332 | 0.285492 | 0.072* | |
C2 | 0.7649 (5) | 0.30983 (14) | 0.6497 (3) | 0.0667 (7) | |
H2 | 0.931108 | 0.317126 | 0.703333 | 0.080* | |
C10 | 0.4457 (5) | 0.58135 (13) | 0.1043 (3) | 0.0713 (8) | |
H10A | 0.570546 | 0.572318 | 0.049089 | 0.086* | |
H10B | 0.499351 | 0.622958 | 0.166698 | 0.086* | |
C5 | 0.2734 (5) | 0.28695 (15) | 0.4909 (3) | 0.0713 (8) | |
H5 | 0.107754 | 0.278384 | 0.437693 | 0.086* | |
C3 | 0.6258 (5) | 0.25482 (14) | 0.6791 (3) | 0.0745 (8) | |
H3 | 0.696946 | 0.223507 | 0.755363 | 0.089* | |
C4 | 0.3833 (5) | 0.24349 (15) | 0.6006 (3) | 0.0760 (8) | |
H4 | 0.292584 | 0.204613 | 0.624028 | 0.091* | |
C11 | 0.1971 (5) | 0.59444 (16) | 0.0056 (3) | 0.0935 (10) | |
H11A | 0.149807 | 0.553780 | −0.058508 | 0.140* | |
H11B | 0.204101 | 0.637068 | −0.051138 | 0.140* | |
H11C | 0.073960 | 0.601063 | 0.061479 | 0.140* | |
H1 | 0.879 (5) | 0.4339 (15) | 0.520 (3) | 0.087 (10)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0631 (11) | 0.0688 (12) | 0.0625 (11) | −0.0022 (9) | 0.0009 (9) | 0.0064 (9) |
O2 | 0.0672 (13) | 0.0828 (13) | 0.0715 (13) | −0.0150 (10) | 0.0001 (10) | 0.0024 (10) |
N1 | 0.0537 (14) | 0.0712 (15) | 0.0544 (13) | −0.0052 (12) | 0.0021 (12) | −0.0023 (12) |
C1 | 0.0522 (15) | 0.0606 (16) | 0.0496 (14) | −0.0010 (12) | 0.0101 (12) | −0.0062 (13) |
C6 | 0.0500 (15) | 0.0628 (15) | 0.0530 (14) | 0.0000 (12) | 0.0082 (12) | −0.0084 (13) |
C9 | 0.0573 (17) | 0.0670 (17) | 0.0524 (15) | 0.0007 (14) | 0.0054 (14) | −0.0125 (14) |
C8 | 0.0564 (16) | 0.0586 (15) | 0.0486 (14) | 0.0021 (12) | 0.0054 (12) | −0.0056 (13) |
C7 | 0.0487 (15) | 0.0709 (17) | 0.0557 (15) | 0.0014 (13) | 0.0021 (12) | −0.0063 (14) |
C2 | 0.0571 (16) | 0.0769 (18) | 0.0607 (17) | 0.0033 (14) | 0.0046 (13) | 0.0009 (15) |
C10 | 0.0766 (19) | 0.0626 (17) | 0.0715 (18) | −0.0028 (14) | 0.0127 (15) | 0.0068 (14) |
C5 | 0.0549 (16) | 0.0793 (18) | 0.0742 (19) | −0.0090 (14) | 0.0056 (14) | −0.0001 (16) |
C3 | 0.0708 (19) | 0.0766 (19) | 0.0727 (19) | 0.0011 (15) | 0.0115 (16) | 0.0111 (15) |
C4 | 0.0697 (19) | 0.0777 (19) | 0.078 (2) | −0.0072 (14) | 0.0136 (16) | 0.0097 (16) |
C11 | 0.088 (2) | 0.089 (2) | 0.091 (2) | 0.0041 (17) | −0.0015 (18) | 0.0239 (18) |
O1—C9 | 1.324 (3) | C2—H2 | 0.9500 |
O1—C10 | 1.455 (3) | C2—C3 | 1.367 (3) |
O2—C9 | 1.217 (3) | C10—H10A | 0.9900 |
N1—C1 | 1.368 (3) | C10—H10B | 0.9900 |
N1—C8 | 1.374 (3) | C10—C11 | 1.491 (3) |
N1—H1 | 0.84 (3) | C5—H5 | 0.9500 |
C1—C6 | 1.406 (3) | C5—C4 | 1.359 (4) |
C1—C2 | 1.394 (3) | C3—H3 | 0.9500 |
C6—C7 | 1.416 (3) | C3—C4 | 1.389 (4) |
C6—C5 | 1.404 (3) | C4—H4 | 0.9500 |
C9—C8 | 1.454 (3) | C11—H11A | 0.9800 |
C8—C7 | 1.366 (3) | C11—H11B | 0.9800 |
C7—H7 | 0.9500 | C11—H11C | 0.9800 |
C9—O1—C10 | 117.45 (19) | O1—C10—H10A | 110.4 |
C1—N1—C8 | 108.9 (2) | O1—C10—H10B | 110.4 |
C1—N1—H1 | 127 (2) | O1—C10—C11 | 106.8 (2) |
C8—N1—H1 | 123 (2) | H10A—C10—H10B | 108.6 |
N1—C1—C6 | 107.6 (2) | C11—C10—H10A | 110.4 |
N1—C1—C2 | 130.2 (2) | C11—C10—H10B | 110.4 |
C2—C1—C6 | 122.2 (2) | C6—C5—H5 | 120.3 |
C1—C6—C7 | 106.9 (2) | C4—C5—C6 | 119.3 (2) |
C5—C6—C1 | 118.3 (2) | C4—C5—H5 | 120.3 |
C5—C6—C7 | 134.8 (2) | C2—C3—H3 | 119.1 |
O1—C9—C8 | 112.1 (2) | C2—C3—C4 | 121.8 (3) |
O2—C9—O1 | 123.6 (2) | C4—C3—H3 | 119.1 |
O2—C9—C8 | 124.3 (2) | C5—C4—C3 | 121.3 (3) |
N1—C8—C9 | 120.5 (2) | C5—C4—H4 | 119.4 |
C7—C8—N1 | 109.2 (2) | C3—C4—H4 | 119.4 |
C7—C8—C9 | 130.3 (2) | C10—C11—H11A | 109.5 |
C6—C7—H7 | 126.4 | C10—C11—H11B | 109.5 |
C8—C7—C6 | 107.3 (2) | C10—C11—H11C | 109.5 |
C8—C7—H7 | 126.4 | H11A—C11—H11B | 109.5 |
C1—C2—H2 | 121.4 | H11A—C11—H11C | 109.5 |
C3—C2—C1 | 117.2 (2) | H11B—C11—H11C | 109.5 |
C3—C2—H2 | 121.4 |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O2i | 0.84 (3) | 2.08 (3) | 2.877 (3) | 158 (3) |
Symmetry code: (i) −x+2, −y+1, −z+1. |
Funding information
The authors wish to thank Georgia Southern University and the Department of Chemistry and Biochemistry for financial support of the department X-ray facility, and Georgia Southern College of Science and Mathematics Office of Undergraduate Research for partial support.
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