Ethyl 1H-indole-2-carboxyl­ate

The synthesis and structure of 1H-indole-2-carboxyl­ate is presented.

Abstract

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 R ² ₂(10) ring motifs in the crystal.

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, (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.

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.

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) .

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 ▸)
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[F 2 > 2σ(F 2)], wR(F 2), 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
Δρmax, Δρmin (e Å−3)	0.28, −0.16

Computer programs: CrysAlis PRO (Rigaku OD, 2018 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL (Sheldrick, 2015b ▸) and OLEX2 (Dolomanov et al., 2009 ▸).

Supplementary Material

CCDC reference: 2026531

Additional supporting information: crystallographic information; 3D view; checkCIF report

full crystallographic data

Crystal data

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

Data collection

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

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

Special details

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.

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

	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)*

Atomic displacement parameters (Ų)

	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)

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)

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 Statement

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.