Ethyl 1H-indole-2-carboxyl­ate

Lynch, W.E.; Whitlock, C.R.; Padgett, C.W.

doi:10.1107/S2414314620012055

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 5| Part 9| September 2020| x201205

https://doi.org/10.1107/S2414314620012055

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Ethyl 1H-indole-2-carboxylate

Will E. Lynch,^a ^* Christine R. Whitlock ^a and Clifford W. Padgett ^a

^aGeorgia Southern University, Department of Chemistry and Biochemistry, Box 8064, Statesboro, GA 30460, USA
^*Correspondence e-mail: wlynch@georgiasouthern.edu

Edited by S. Bernès, Benemérita Universidad Autónoma de Puebla, México (Received 3 August 2020; accepted 31 August 2020; online 8 September 2020)

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 esters can easily be prepared from 1H-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 ).

Herein we report the crystal structure of ethyl 1H-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 space group P2₁/c (Fig. 2). The crystal structure 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.

Table 1
Hydrogen-bond geometry (Å, °)

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.

Figure 1
A view of the molecular structure of the title compound, with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
Crystal packing diagram of title compound viewed along [100]. Hydrogen bonds are coloured red.

Synthesis 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 refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₁H₁₁NO₂
M_r	189.21
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	170
a, b, c (Å)	5.5622 (7), 18.891 (2), 9.6524 (13)
β (°)	104.454 (13)
V (Å³)	982.1 (2)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.09
Crystal size (mm)	0.4 × 0.05 × 0.05

Data collection
Diffractometer	Rigaku XtaLAB mini
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction Ltd, Yarnton, England.]$ )
T_min, T_max	0.998, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	5586, 1804, 991
R_int	0.047
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.144, 1.01
No. of reflections	1804
No. of parameters	132
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.16
Computer programs: CrysAlis PRO (Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction Ltd, Yarnton, England.]$ ), SHELXT (Sheldrick, 2015a ), SHELXL (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 2026531

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314620012055/bh4054sup1.cif

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

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: 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).

Ethyl 1H-indole-2-carboxylate top

Crystal data top

C₁₁H₁₁NO₂	F(000) = 400
M_r = 189.21	D_x = 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

Data collection top

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	R_int = 0.047
ω scans	θ_max = 25.3°, θ_min = 2.2°
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2018)	h = −6→6
T_min = 0.998, T_max = 1.000	k = −22→22
5586 measured reflections	l = −6→11

Refinement top

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(F_o²) + (0.0611P)²] where P = (F_o² + 2F_c²)/3
1804 reflections	(Δ/σ)_max < 0.001
132 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.16 e Å⁻³

Special details top

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 U_iso(H) = 1.2U_eq(C) or U_iso(H) = 1.5U_eq(C) for C(H) and CH₃ groups, respectively. Hydrogen atom of the N—H group was refined freely.

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

	x	y	z	U_iso*/U_eq
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)*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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

Hydrogen-bond geometry (Å, º) top

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.

References

Almutairi, M. S., Ghabbour, H. A. & Attia, M. I. (2017). Z. Kristallogr. New Cryst. Struct. 232, 431–432. Web of Science CSD CrossRef CAS Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Jobson, A. G., Lountos, G. T., Lorenzi, P. L., Llamas, J., Connelly, J., Cerna, D., Tropea, J. E., Onda, A., Zoppoli, G., Kondapaka, S., Zhang, G., Caplen, N. J., Cardellina, J. H., Yoo, S. S., Monks, A., Self, C., Waugh, D. S., Shoemaker, R. H. & Pommier, Y. (2009). J. Pharmacol. Exp. Ther. 331, 816–826. Web of Science CrossRef PubMed CAS Google Scholar
Kipp, C. & Young, A. R. (1999). Photochem. Photobiol. 70, 191–198. Web of Science CrossRef PubMed CAS Google Scholar
Liu, Z., Tang, L., Zhu, H., Xu, T., Qiu, C., Zheng, S., Gu, Y., Feng, J., Zhang, Y. & Liang, G. (2016). J. Med. Chem. 59, 4637–4650. Web of Science CrossRef CAS PubMed Google Scholar
Lu, J.-J., Fu, L., Tang, Z., Zhang, C., Qin, L., Wang, J., Yu, Z., Shi, D., Xiao, X., Xie, F., Huang, W. & Deng, W. (2016). Oncotarget, 7, 2985–3001. Web of Science CrossRef PubMed Google Scholar
Morzyk-Ociepa, B., Michalska, D. & Pietraszko, A. (2004). J. Mol. Struct. 688, 79–86. Web of Science CSD CrossRef CAS Google Scholar
Ohtani, K.-I., Tanaka, H., Yoneda, Y., Yasuda, H., Ito, A., Nagata, R. & Nakamura, M. (2002). Brain Res. 944, 165–173. Web of Science CrossRef PubMed CAS Google Scholar
Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction Ltd, Yarnton, England. Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Stempel, E. & Gaich, T. (2016). Acc. Chem. Res. 49, 2390–2402. Web of Science CrossRef CAS PubMed Google Scholar
Terent'ev, A. P., Yudin, L. G., Smirnova, G. V. & Kost, A. N. (1969). Chem. Heterocycl. Compd. 3, 455–455. Google Scholar

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