Methyl 4-(tri­fluoro­meth­yl)-1H-pyrrole-3-carboxyl­ate

Suchetan, P.A.; Sreenivasa, S.; Palakshamurthy, B.S.; ManojKumar, K.E.; Madan Kumar, S.; Lokanath, N.K.

doi:10.1107/S160053681302549X

organic compounds

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ISSN: 2056-9890

Volume 69| Part 10| October 2013| Page o1566

doi:10.1107/S160053681302549X

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Methyl 4-(trifluoromethyl)-1H-pyrrole-3-carboxylate

P. A. Suchetan,^a S. Sreenivasa,^b ^* B. S. Palakshamurthy,^c K. E. ManojKumar,^b S Madan Kumar ^d and N. K. Lokanath ^d

^aDepartment of Studies and Research in Chemistry, U.C.S., Tumkur University, Tumkur, Karnataka 572 103, India, ^bDepartment of Studies and Research in Chemistry, Tumkur University, Tumkur, Karnataka 572 103, India, ^cDepartment of Studies and Research in Physics, U.C.S., Tumkur University, Tumkur, Karnataka 572 103, India, and ^dDepartment of Studies in Physics, University of Mysore, Manasagangotri, Mysore, India
^*Correspondence e-mail: drsreenivasa@yahoo.co.in

(Received 9 September 2013; accepted 13 September 2013; online 18 September 2013)

In the title compound, C₇H₆F₃NO₂, all the non-H atoms except for one of the F atoms lie on a crystallographic mirror plane. In the crystal, the molecules are linked into inversion dimers by pairs of C—H⋯F interactions, forming R₂²(10) loops. These dimers are connected into C(6) chains along [001] through N—H⋯O hydrogen bonds. Aromatic π–π stacking interactions [centroid-centroid separation = 3.8416 (10) A°] connect the molecules into a three-dimensional network.

CCDC reference: 960926

Related literature

For background to the pharmacological activity of pyrrole derivatives, see: Toja et al. (1987 ); Muchowski et al. (1985 ); Dannhardt et al. (2000 ); Burnham et al. (1998 ); Krowicki et al. (1988 ).

Experimental

Crystal data

C₇H₆F₃NO₂
M_r = 193.13
Monoclinic, C 2/m
a = 16.643 (2) Å
b = 7.1118 (10) Å
c = 6.9618 (11) Å
β = 98.903 (7)°
V = 814.1 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.16 mm⁻¹
T = 293 K
0.24 × 0.22 × 0.20 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ) T_min = 0.963, T_max = 0.969
3752 measured reflections
707 independent reflections
645 reflections with I > 2σ(I)
R_int = 0.076

Refinement

R[F² > 2σ(F²)] = 0.065
wR(F²) = 0.180
S = 1.09
707 reflections
81 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.32 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N—H⋯O1ⁱ	0.83 (6)	2.03 (5)	2.810 (4)	156
C5—H5⋯F1ⁱⁱ	0.93	2.52	3.442 (4)	171
Symmetry codes: (i) x, y, z-1; (ii) -x+1, y, -z.

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT-Plus (Bruker, 2009); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2008 ); software used to prepare material for publication: SHELXL97.

Supporting information

CCDC reference: 960926

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: 10.1107/S160053681302549X/hb7136sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053681302549X/hb7136Isup2.hkl

Supporting information file. DOI: 10.1107/S160053681302549X/hb7136Isup3.cml

checkCIF report

Comment top

Pyrrole derivatives are given considerable attention due to their synthetic importance and their extensive use in drug discovery (Toja et al., 1987) and pharmacological activity such as anti-inflammatory (Muchowski et al., 1985), cytotoxicity (Dannhardt et al., 2000), in vitro cytotoxic activity against solid tumour models (Burnham et al., 1998), antitumour agents (Krowicki et al., 1988]) etc. As part of our studies in this area, the title compound was synthesized and its structure determined.

In the title compound, C₇H₆F₃NO₂, the C=O and O—C(methoxy) bonds are syn to each other (Fig 1). The molecules are linked into inversion dimers along a axis through C5—H5···F1 interactions, thus forming R₂²(10) loops (Fig 2). These dimers are further connected into C(6) chains through strong N—H···O1 hydrogen bonds along c axis (Fig 2). Further, π-π stacking interactions [centroid-centroid separation = 3.8416 (10) A°] connects the molecules into a three dimensional network (Fig 3).

Related literature top

For background to the pharmacological activity of pyrrole derivatives, see: Toja et al. (1987); Muchowski et al. (1985); Dannhardt et al. (2000); Burnham et al. (1998); Krowicki et al. (1988).

Experimental top

Sodium hydride (0.02 mol) and methyl 4,4,4-trifluorobut-2-enoate (0.01 mol) were taken in dry Tetrahydrofuran (THF). The reaction mixture was stirred for 15 min. Toluenesulfonylmethyl isocyanide (TosMIC, 0.01 mol) was added to the reaction mixture and the mixture was heated to 50°C for 2 h. Reaction was monitored by TLC. Ethyl acetate was added to the mixture. Sodium hydride was quenched by using saturated solution of ammonium chloride and the organic layer was separated, dried and concentrated. The crude compound was purified by column chromatography using petroleum ether / ethyl acetate (7:3) as eluent to give the title compound as a colorless solid.

Colourless prisms were obtained from slow evapouration of the solution of the compound in a mixture of petroleum ether/ethyl acetate (7:3).

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT-Plus (Bruker, 2009); data reduction: SAINT-Plus (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure of the title compound, showing displacement ellipsoids drawn at the 50% probability level. Symmetry code for F2a: (x, -y, z).
	Fig. 2. Molecular packing in the title compound displaying R₂²(10) loops and C(6) chains. H atoms not involved in H-bonding is omitted for clarity.
	Fig. 3. π-π stacking interactions observed in the crystal structure.

Methyl 4-(trifluoromethyl)-1H-pyrrole-3-carboxylate top

Crystal data top

C₇H₆F₃NO₂	prism
M_r = 193.13	D_x = 1.576 Mg m⁻³
Monoclinic, C2/m	Melting point: 405 K
Hall symbol: -C 2y	Mo Kα radiation, λ = 0.71073 Å
a = 16.643 (2) Å	Cell parameters from 645 reflections
b = 7.1118 (10) Å	θ = 3.0–24.4°
c = 6.9618 (11) Å	µ = 0.16 mm⁻¹
β = 98.903 (7)°	T = 293 K
V = 814.1 (2) Å³	Prism, colourless
Z = 4	0.24 × 0.22 × 0.20 mm
F(000) = 392

Data collection top

Bruker APEXII CCD diffractometer	707 independent reflections
Radiation source: fine-focus sealed tube	645 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.076
Detector resolution: 1.08 pixels mm^-1	θ_max = 24.4°, θ_min = 3.0°
ω scans	h = −19→19
Absorption correction: multi-scan (SADABS; Bruker, 2009)	k = −8→8
T_min = 0.963, T_max = 0.969	l = −3→7
3752 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.065	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.180	w = 1/[σ²(F_o²) + (0.1299P)² + 0.3175P] where P = (F_o² + 2F_c²)/3
S = 1.09	(Δ/σ)_max < 0.001
707 reflections	Δρ_max = 0.37 e Å⁻³
81 parameters	Δρ_min = −0.32 e Å⁻³
0 restraints	Extinction correction: SHELXL, Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 constraints	Extinction coefficient: 0.08 (2)
Primary atom site location: structure-invariant direct methods

Crystal data top

C₇H₆F₃NO₂	V = 814.1 (2) Å³
M_r = 193.13	Z = 4
Monoclinic, C2/m	Mo Kα radiation
a = 16.643 (2) Å	µ = 0.16 mm⁻¹
b = 7.1118 (10) Å	T = 293 K
c = 6.9618 (11) Å	0.24 × 0.22 × 0.20 mm
β = 98.903 (7)°

Data collection top

Bruker APEXII CCD diffractometer	707 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2009)	645 reflections with I > 2σ(I)
T_min = 0.963, T_max = 0.969	R_int = 0.076
3752 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.065	0 restraints
wR(F²) = 0.180	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	Δρ_max = 0.37 e Å⁻³
707 reflections	Δρ_min = −0.32 e Å⁻³
81 parameters

Special details top

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
H	0.275 (3)	0.0000	−0.341 (8)	0.073 (13)*
C1	0.0515 (2)	0.0000	0.2701 (6)	0.0765 (12)
H1A	0.0456	0.1254	0.3171	0.115*	0.50
H1B	0.0701	−0.0816	0.3777	0.115*	0.50
H1C	0.0000	−0.0438	0.2042	0.115*	0.50
C2	0.18890 (17)	0.0000	0.2149 (4)	0.0436 (9)
C3	0.24211 (16)	0.0000	0.0673 (4)	0.0391 (8)
C4	0.21641 (19)	0.0000	−0.1280 (4)	0.0480 (8)
H4	0.1625	0.0000	−0.1881	0.058*
C5	0.3504 (2)	0.0000	−0.0863 (5)	0.0563 (10)
H5	0.4034	0.0000	−0.1137	0.068*
C6	0.32889 (16)	0.0000	0.0952 (4)	0.0443 (8)
C7	0.38690 (18)	0.0000	0.2762 (5)	0.0544 (9)
F1	0.46353 (14)	0.0000	0.2439 (4)	0.1048 (12)
F2	0.38017 (10)	0.1475 (2)	0.3904 (2)	0.0853 (8)
N	0.28189 (18)	0.0000	−0.2200 (5)	0.0587 (9)
O1	0.20994 (15)	0.0000	0.3872 (3)	0.0718 (9)
O2	0.11034 (12)	0.0000	0.1358 (3)	0.0586 (8)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.057 (2)	0.116 (3)	0.058 (3)	0.000	0.0154 (17)	0.000
C2	0.0503 (16)	0.0517 (15)	0.026 (2)	0.000	−0.0038 (11)	0.000
C3	0.0478 (15)	0.0422 (13)	0.0235 (19)	0.000	−0.0066 (11)	0.000
C4	0.0574 (17)	0.0589 (16)	0.0237 (19)	0.000	−0.0065 (12)	0.000
C5	0.0570 (17)	0.0708 (19)	0.042 (2)	0.000	0.0092 (14)	0.000
C6	0.0491 (16)	0.0483 (14)	0.0331 (18)	0.000	−0.0007 (11)	0.000
C7	0.0481 (16)	0.0667 (17)	0.045 (2)	0.000	−0.0052 (13)	0.000
F1	0.0486 (13)	0.185 (3)	0.076 (2)	0.000	−0.0056 (11)	0.000
F2	0.0959 (13)	0.0903 (13)	0.0570 (14)	−0.0019 (7)	−0.0278 (8)	−0.0240 (7)
N	0.077 (2)	0.0781 (18)	0.020 (2)	0.000	0.0034 (13)	0.000
O1	0.0645 (15)	0.125 (2)	0.0230 (17)	0.000	−0.0013 (10)	0.000
O2	0.0470 (13)	0.0914 (16)	0.0352 (16)	0.000	−0.0006 (9)	0.000

Geometric parameters (Å, º) top

C1—O2	1.455 (4)	C4—H4	0.9300
C1—H1A	0.9600	C5—N	1.356 (5)
C1—H1B	0.9600	C5—C6	1.366 (5)
C1—H1C	0.9600	C5—H5	0.9300
C2—O1	1.196 (4)	C6—C7	1.464 (5)
C2—O2	1.338 (4)	C7—F1	1.329 (4)
C2—C3	1.457 (4)	C7—F2ⁱ	1.332 (3)
C3—C4	1.360 (4)	C7—F2	1.332 (3)
C3—C6	1.427 (4)	N—H	0.84 (5)
C4—N	1.347 (4)

O2—C1—H1A	109.5	N—C5—H5	125.6
O2—C1—H1B	109.5	C6—C5—H5	125.6
H1A—C1—H1B	109.5	C5—C6—C3	106.2 (3)
O2—C1—H1C	109.5	C5—C6—C7	124.3 (3)
H1A—C1—H1C	109.5	C3—C6—C7	129.5 (3)
H1B—C1—H1C	109.5	F1—C7—F2ⁱ	105.81 (19)
O1—C2—O2	121.9 (3)	F1—C7—F2	105.81 (19)
O1—C2—C3	126.3 (3)	F2ⁱ—C7—F2	104.0 (3)
O2—C2—C3	111.8 (3)	F1—C7—C6	112.2 (3)
C4—C3—C6	106.9 (3)	F2ⁱ—C7—C6	114.12 (17)
C4—C3—C2	125.0 (3)	F2—C7—C6	114.12 (17)
C6—C3—C2	128.1 (3)	C4—N—C5	109.3 (3)
N—C4—C3	108.8 (3)	C4—N—H	119 (3)
N—C4—H4	125.6	C5—N—H	131 (3)
C3—C4—H4	125.6	C2—O2—C1	116.6 (3)
N—C5—C6	108.8 (3)

Symmetry code: (i) x, −y, z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N—H···O1ⁱⁱ	0.83 (6)	2.03 (5)	2.810 (4)	156
C5—H5···F1ⁱⁱⁱ	0.93	2.52	3.442 (4)	171

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

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N—H···O1ⁱ	0.83 (6)	2.03 (5)	2.810 (4)	156
C5—H5···F1ⁱⁱ	0.93	2.52	3.442 (4)	171

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

Acknowledgements

The authors acknowledge the IOE X-ray diffractometer Facility, University of Mysore, Mysore, for collecting the data.

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