Methyl 1-methyl-1H-indole-3-carboxyl­ate

Furuya, T.; Yagi, S.; Yamazaki, S.; Haraguchi, T.; Akitsu, T.; Mahesha, N.; Sagar, B.K.; Yathirajan, H.S.

doi:10.1107/S2414314618017285

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 3| Part 12| December 2018| x181728

https://doi.org/10.1107/S2414314618017285

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Methyl 1-methyl-1H-indole-3-carboxylate

Tetsundo Furuya,^a Shiomi Yagi,^a Shu Yamazaki,^a Tomoyuki Haraguchi,^a Takashiro Akitsu,^a ^* Ninganayaka Mahesha,^b Belakavadi K. Sagar ^b and Hemmige S. Yathirajan ^b

^aDepartment of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan, and ^bDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570 006, India
^*Correspondence e-mail: akitsu2@rs.tus.ac.jp

Edited by L. Van Meervelt, Katholieke Universiteit Leuven, Belgium (Received 3 December 2018; accepted 5 December 2018; online 11 December 2018)

The title indole derivative, C₁₁H₁₁NO₂, was synthesized from 1-methyl-1H-indole-3-carboxylic acid and methanol. The molecule is planar as it is situated on a mirror plane present in the space group Pbcm. In the crystal, molecules form three kinds of intermolecular C—H⋯O hydrogen bonds, resulting in a sheet structure in the ab plane. Parallel sheets interact by C—H⋯π stacking, stabilizing the crystal packing.

Keywords: indole; crystal structure; carboxylate; hydrogen bonding; coplanar.

CCDC reference: 1883282

Structure description

The indole moiety is found in a large array of natural products and pharmaceuticals and widely used for its anti-allergic (Shigenaga et al., 1993 ), central-nervous-system depressant (Sen Gupta et al., 1982 ) and muscle relaxant (Butera et al., 1978 ) properties. Indolecarboxylic acid derivatives show biological activity (Morzyk-Ociepa et al., 2004 ). 5-Fluoroindole-3-acetic acid has plant-growth regulating activity (Antolic et al., 1996 ). A comprehensive review on the biological importance of the indole nucleus in recent years was published by Sharma et al. (2010 ) and the biomedical importance of indoles was reported on by Kaushik et al. (2013 ). Reviews on indoles as anticancer agents (El Sayed et al., 2015 ) and on recent developments of indole-containing antiviral agents (Zhang et al., 2015 ) have been published.

The crystal structures of similar compounds viz. indole-3-carboxylic acid (Smith et al., 2003 ), indole-2-carboxylic acid (Morzyk-Ociepa et al., 2004), methyl 5-fluoro-1H-indole-2-carboxylate (Harrison et al., 2006 ), 5-fluoro-1H-indole-2-carbohydrazide (Harrison et al., 2006a ), methyl 5-chloro-1H-indole-2-carboxylate (Butcher et al., 2006 ), methyl 5-bromo-1H-indole-2-carboxylate (Butcher et al., 2007 ), (4-bromophenyl)(1H-indol-7-yl)methanone (Dutkiewicz et al., 2009 ), 6-fluoro-1H-indole-3-carboxylic acid (Lou & Luo, 2012 ), 5-fluoro-1H-indole-3-carboxylic acid (Lu et al., 2012 ) and 6-bromo-1H-indole-3-carboxylic acid (Zhao & Wang, 2012 ) have been reported.

The molecular structure of the title compound consists of an indole substituted by one methyl and one carboxymethyl group (Fig. 1). The molecule is planar as it is situated on a mirror plane belonging to the space group Pbcm (except for hydrogen atoms H10B, H10C, H11B and H11C). The N1—C11 bond length of the methyl substituent is 1.453 (3) Å, the C7—C9 bond length of the carboxymethyl substituent is 1.467 (3) Å and the O2—C10 bond of the carboxymethyl substituent is 1.445 (3) Å.

Figure 1
The molecular structure of the title compound, showing the atom-numbering scheme and displacement ellipsoids drawn at the 50% probability level.

In the crystal, molecules are connected along the a- and b-axis directions by C—H⋯O hydrogen bonds, forming two-dimensional sheets (Table 1 and Fig. 2). In addition, a weak C—H⋯π interaction C11—H11B⋯Cg1 (2.69 Å) is observed between neighboring sheets (Table 1 and Fig. 3; Cg1 is the centroid of the C1–C6 ring). In the packing of the similar structure methyl indole-3-carboxylate (Hu et al., 2005 ), the molecules are linked by intermolecular hydrogen bonds and form chains along the b-axis direction.

Table 1
Hydrogen-bond geometry (Å, °) for (I)

Cg1 is the centroid of the C1–C6 ring.

D—H⋯A	D—H	H⋯A	A⋯H	D—H⋯A
C4—H4⋯O2ⁱ	0.95	2.39	3.318 (3)	167
C11—H11A⋯O1ⁱⁱ	0.98	2.53	3.505 (4)	176
C2—H2⋯O1ⁱⁱ	0.95	2.46	3.400 (3)	172
C11—H11B⋯Cg1ⁱⁱⁱ	0.98	2.69	3.412	131
Symmetry codes: (i) x − 1, y, z; (ii) −x + 1, y − $[{1\over 2}]$ , −z + $[{3\over 2}]$ ; (iii) −x + 1, −y + 1, z − $[{1\over 2}]$ .

Figure 2
A view of the C—H⋯O hydrogen bonds (dashed lines) present in the crystal structure of the title compound.

Figure 3
Part of the crystal packing showing the C—H⋯π stacking interactions. Cg1 is the centroid of the C1–C6 ring.

Synthesis and crystallization

1-Methyl-1H-indole-3-carboxylic acid (Sigma–Aldrich) (2 g) was taken in a 100 ml round-bottomed flask. 20 ml of methanol and a catalytic amount of conc. H₂SO₄ (2 drops) was added and the reaction mixture was refluxed overnight. The completion of the reaction was confirmed by TLC and the reaction mixture was quenched with water; the precipitate formed was collected by filtration and dried. The product was recrystallized from methanol solution (m.p. 410 K). IR (KBr, cm⁻¹): 1704 (C=O). The UV–vis spectrum was measured in MeOH solution (concentration ≃ 1.0×10 ⁻² mM): λ_max = 297 nm.

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	Orthorhombic, Pbcm
Temperature (K)	173
a, b, c (Å)	8.3019 (17), 16.628 (3), 6.7622 (14)
V (Å³)	933.5 (3)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.09
Crystal size (mm)	0.50 × 0.24 × 0.17

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2013 )
T_min, T_max	0.88, 0.98
No. of measured, independent and observed [I > 2σ(I)] reflections	4700, 1142, 1053
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.065, 0.208, 1.12
No. of reflections	1142
No. of parameters	85
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.72, −0.98
Computer programs: APEX2 and SAINT (Bruker, 2013), SHELXT2014 (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), ORTEP-3 for Windows (Farrugia, 2012 ) and SHELXTL (Sheldrick, 2008 ).

Structural data

CCDC reference: 1883282

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314618017285/vm4039sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314618017285/vm4039Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314618017285/vm4039Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Methyl 1-methyl-1H-indole-3-carboxylate top

Crystal data top

C₁₁H₁₁NO₂	D_x = 1.346 Mg m⁻³
M_r = 189.21	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbcm	Cell parameters from 3337 reflections
a = 8.3019 (17) Å	θ = 2.5–27.5°
b = 16.628 (3) Å	µ = 0.09 mm⁻¹
c = 6.7622 (14) Å	T = 173 K
V = 933.5 (3) Å³	Prism, colorless
Z = 4	0.50 × 0.24 × 0.17 mm
F(000) = 400

Data collection top

Bruker APEXII CCD diffractometer	1142 independent reflections
Radiation source: fine-focus sealed tube	1053 reflections with I > 2σ(I)
Detector resolution: 8.3333 pixels mm^-1	R_int = 0.018
φ and ω scans	θ_max = 27.5°, θ_min = 2.5°
Absorption correction: multi-scan (SADABS; Bruker, 2013)	h = −10→10
T_min = 0.88, T_max = 0.98	k = −20→21
4700 measured reflections	l = −8→6

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.065	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.208	H-atom parameters constrained
S = 1.12	w = 1/[σ²(F_o²) + (0.1286P)² + 0.595P] where P = (F_o² + 2F_c²)/3
1142 reflections	(Δ/σ)_max < 0.001
85 parameters	Δρ_max = 0.72 e Å⁻³
0 restraints	Δρ_min = −0.98 e Å⁻³

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. All H atoms were located in difference Fourier maps. C-bound H atoms were constrained using a riding model [C—H = 0.95 Å and U_iso(H) = 1.2U_eq(C) for indole H atoms, and C—H = 0.98 Å and U_iso(H) = 1.5U_eq(C) for methyl H atoms].

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.6055 (2)	0.79479 (11)	0.75	0.0350 (6)
N1	0.6285 (3)	0.52415 (12)	0.75	0.0240 (5)
O2	0.8514 (2)	0.73850 (12)	0.75	0.0445 (7)
C8	0.7251 (3)	0.58886 (12)	0.75	0.0179 (5)
H8	0.8395	0.589	0.75	0.021*
C7	0.6279 (3)	0.65316 (14)	0.75	0.0233 (6)
C6	0.4631 (3)	0.62971 (13)	0.75	0.0225 (6)
C1	0.4691 (3)	0.54488 (14)	0.75	0.0228 (6)
C11	0.6944 (3)	0.44316 (16)	0.75	0.0290 (6)
H11A	0.606	0.4041	0.75	0.044*
H11B	0.7607	0.4354	0.6317	0.044*	0.5
H11C	0.7607	0.4354	0.8683	0.044*	0.5
C9	0.6900 (3)	0.73575 (15)	0.75	0.0254 (6)
C2	0.3304 (3)	0.49675 (16)	0.75	0.0284 (6)
H2	0.3362	0.4397	0.75	0.034*
C5	0.3130 (3)	0.66896 (16)	0.75	0.0277 (6)
H5	0.3062	0.726	0.75	0.033*
C4	0.1759 (3)	0.62199 (17)	0.75	0.0315 (7)
H4	0.0733	0.6473	0.75	0.038*
C3	0.1847 (3)	0.53694 (18)	0.75	0.0325 (7)
H3	0.0877	0.5066	0.75	0.039*
C10	0.9213 (4)	0.81809 (17)	0.75	0.0488 (10)
H10A	1.0391	0.8138	0.75	0.073*
H10B	0.8862	0.8472	0.6317	0.073*	0.5
H10C	0.8862	0.8472	0.8683	0.073*	0.5

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0301 (10)	0.0179 (9)	0.0569 (13)	0.0022 (7)	0	0
N1	0.0231 (11)	0.0175 (10)	0.0315 (11)	0.0010 (8)	0	0
O2	0.0240 (10)	0.0187 (10)	0.0908 (19)	−0.0017 (7)	0	0
C8	0.0178 (11)	0.0123 (10)	0.0235 (11)	0.0001 (7)	0	0
C7	0.0244 (12)	0.0181 (12)	0.0273 (12)	0.0022 (9)	0	0
C6	0.0251 (13)	0.0181 (11)	0.0244 (11)	−0.0001 (9)	0	0
C1	0.0232 (13)	0.0198 (11)	0.0253 (12)	0.0047 (9)	0	0
C11	0.0314 (13)	0.0181 (12)	0.0375 (14)	0.0056 (9)	0	0
C9	0.0244 (12)	0.0202 (13)	0.0315 (12)	0.0008 (8)	0	0
C2	0.0268 (13)	0.0223 (12)	0.0360 (13)	−0.0003 (10)	0	0
C5	0.0268 (13)	0.0219 (12)	0.0343 (13)	0.0049 (9)	0	0
C4	0.0236 (13)	0.0302 (14)	0.0407 (15)	0.0043 (10)	0	0
C3	0.0226 (12)	0.0300 (14)	0.0450 (16)	−0.0015 (10)	0	0
C10	0.0281 (14)	0.0199 (13)	0.098 (3)	−0.0039 (10)	0	0

Geometric parameters (Å, º) top

O1—C9	1.206 (3)	C11—H11A	0.98
N1—C8	1.342 (3)	C11—H11B	0.98
N1—C1	1.368 (3)	C11—H11C	0.98
N1—C11	1.453 (3)	C2—C3	1.382 (4)
O2—C9	1.341 (3)	C2—H2	0.95
O2—C10	1.445 (3)	C5—C4	1.380 (4)
C8—C7	1.340 (3)	C5—H5	0.95
C8—H8	0.95	C4—C3	1.416 (4)
C7—C6	1.423 (3)	C4—H4	0.95
C7—C9	1.467 (3)	C3—H3	0.95
C6—C5	1.407 (3)	C10—H10A	0.98
C6—C1	1.412 (3)	C10—H10B	0.98
C1—C2	1.402 (4)	C10—H10C	0.98

C8—N1—C1	112.1 (2)	O1—C9—O2	123.6 (2)
C8—N1—C11	121.2 (2)	O1—C9—C7	123.9 (2)
C1—N1—C11	126.7 (2)	O2—C9—C7	112.5 (2)
C9—O2—C10	115.6 (2)	C3—C2—C1	116.3 (2)
C7—C8—N1	106.3 (2)	C3—C2—H2	121.9
C7—C8—H8	126.9	C1—C2—H2	121.9
N1—C8—H8	126.9	C4—C5—C6	117.9 (2)
C8—C7—C6	111.1 (2)	C4—C5—H5	121.1
C8—C7—C9	122.4 (2)	C6—C5—H5	121.1
C6—C7—C9	126.5 (2)	C5—C4—C3	121.5 (2)
C5—C6—C1	119.7 (2)	C5—C4—H4	119.3
C5—C6—C7	136.5 (2)	C3—C4—H4	119.3
C1—C6—C7	103.9 (2)	C2—C3—C4	121.9 (2)
N1—C1—C2	130.6 (2)	C2—C3—H3	119.0
N1—C1—C6	106.6 (2)	C4—C3—H3	119.0
C2—C1—C6	122.8 (2)	O2—C10—H10A	109.5
N1—C11—H11A	109.5	O2—C10—H10B	109.5
N1—C11—H11B	109.5	H10A—C10—H10B	109.5
H11A—C11—H11B	109.5	O2—C10—H10C	109.5
N1—C11—H11C	109.5	H10A—C10—H10C	109.5
H11A—C11—H11C	109.5	H10B—C10—H10C	109.5
H11B—C11—H11C	109.5

C1—N1—C8—C7	0	C7—C6—C1—C2	180.0
C11—N1—C8—C7	180.0	C10—O2—C9—O1	0
N1—C8—C7—C6	0	C10—O2—C9—C7	180.0
N1—C8—C7—C9	180.0	C8—C7—C9—O1	180.0
C8—C7—C6—C5	180.0	C6—C7—C9—O1	0
C9—C7—C6—C5	0	C8—C7—C9—O2	0
C8—C7—C6—C1	0	C6—C7—C9—O2	180.0
C9—C7—C6—C1	180.0	N1—C1—C2—C3	180.0
C8—N1—C1—C2	180.0	C6—C1—C2—C3	0
C11—N1—C1—C2	0	C1—C6—C5—C4	0
C8—N1—C1—C6	0	C7—C6—C5—C4	180.0
C11—N1—C1—C6	180.0	C6—C5—C4—C3	0
C5—C6—C1—N1	180.0	C1—C2—C3—C4	0
C7—C6—C1—N1	0	C5—C4—C3—C2	0
C5—C6—C1—C2	0

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O2ⁱ	0.95	2.39	3.318 (3)	167
C11—H11A···O1ⁱⁱ	0.98	2.53	3.505 (4)	176
C2—H2···O1ⁱⁱ	0.95	2.46	3.400 (3)	172
C11—H11B···Cg1ⁱⁱⁱ	0.98	2.69	3.412	131

Symmetry codes: (i) x−1, y, z; (ii) −x+1, y−1/2, −z+3/2; (iii) −x+1, −y+1, z−1/2.

Hydrogen-bond geometry (Å, °) for (I) top

Cg1 is the centroid of the C1–C6 ring.

D—H···A	D—H	H···A	A···H	D—H···A
C4—H4···O2ⁱ	0.95	2.39	3.318 (3)	167
C11—H11A···O1ⁱⁱ	0.98	2.53	3.505 (4)	176
C2—H2···O1ⁱⁱ	0.95	2.46	3.400 (3)	172
C11—H11B···Cg1ⁱⁱⁱ	0.98	2.69	3.412	131

Symmetry codes: (i) x-1, y, z; (ii) -x+1, y-1/2, -z+3/2; (iii) -x+1, -y+1, z-1/2.

Acknowledgements

NM is grateful to the University of Mysore for research facilities.

Funding information

HSY is grateful to the UGC, New Delhi for the award of BSR Faculty Fellowship for three years. BKS thanks the UGC, New Delhi, for the award of an RGNF.

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