organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

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

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 ππ stacking inter­actions [centroid-centroid separation = 3.8416 (10) A°] connect the mol­ecules into a three-dimensional network.

Related literature

For background to the pharmacological activity of pyrrole derivatives, see: Toja et al. (1987[Toja, E., Depaoli, A., Tuan, G. & Kettenring, J. (1987). Synthesis, pp. 272-274.]); Muchowski et al. (1985[Muchowski, J. M., Unger, S. H., Ackrell, J., Cheung, P., Cook, J., Gallegra, P., Halpern, O., Koehler, R. & Kluge, A. F. (1985). J. Med. Chem. 28, 1037-1049.]); Dannhardt et al. (2000[Dannhardt, G., Kiefer, W., Kramer, G., Maehrlein, S., Nowe, U. & Fiebich, B. (2000). Eur. J. Med. Chem. 35, 499-510.]); Burnham et al. (1998[Burnham, B. S., Gupton, J. T., Krumpe, K. E., Webb, T., Shuford, J., Bowers, B., Warren, A. E., Barnes, C. & Hall, I. H. (1998). Arch. Pharm. Pharm. Med. Chem. 331, 337-341.]); Krowicki et al. (1988[Krowicki, K., Jan Balzarini, T., Clercq, E. D., Robert, A., Newman, J. & Lawn, J. W. (1988). J. Med. Chem. 31, 341-345.]).

[Scheme 1]

Experimental

Crystal data
  • C7H6F3NO2

  • Mr = 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[Bruker (2009). APEX2, SADABS and SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.963, Tmax = 0.969

  • 3752 measured reflections

  • 707 independent reflections

  • 645 reflections with I > 2σ(I)

  • Rint = 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

  • Δρmax = 0.37 e Å−3

  • Δρmin = −0.32 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Bruker (2009). APEX2, SADABS and SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT-Plus (Bruker, 2009[Bruker (2009). APEX2, SADABS and SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]); software used to prepare material for publication: SHELXL97.

Supporting information


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 OC(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).

Refinement top

The H atom of the NH group was located in a difference map and later refined freely. The other H atoms were positioned with idealized geometry using a riding model with C—H = 0.93–0.96 Å. All H atoms were refined with isotropic displacement parameters (set to 1.2 times of the Ueq of the parent atom).

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
[Figure 1] Fig. 1. Molecular structure of the title compound, showing displacement ellipsoids drawn at the 50% probability level. Symmetry code for F2a: (x, -y, z).
[Figure 2] 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.
[Figure 3] Fig. 3. π-π stacking interactions observed in the crystal structure.
Methyl 4-(trifluoromethyl)-1H-pyrrole-3-carboxylate top
Crystal data top
C7H6F3NO2prism
Mr = 193.13Dx = 1.576 Mg m3
Monoclinic, C2/mMelting point: 405 K
Hall symbol: -C 2yMo Kα radiation, λ = 0.71073 Å
a = 16.643 (2) ÅCell parameters from 645 reflections
b = 7.1118 (10) Åθ = 3.0–24.4°
c = 6.9618 (11) ŵ = 0.16 mm1
β = 98.903 (7)°T = 293 K
V = 814.1 (2) Å3Prism, colourless
Z = 40.24 × 0.22 × 0.20 mm
F(000) = 392
Data collection top
Bruker APEXII CCD
diffractometer
707 independent reflections
Radiation source: fine-focus sealed tube645 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.076
Detector resolution: 1.08 pixels mm-1θmax = 24.4°, θmin = 3.0°
ω scansh = 1919
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
k = 88
Tmin = 0.963, Tmax = 0.969l = 37
3752 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.065H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.180 w = 1/[σ2(Fo2) + (0.1299P)2 + 0.3175P]
where P = (Fo2 + 2Fc2)/3
S = 1.09(Δ/σ)max < 0.001
707 reflectionsΔρmax = 0.37 e Å3
81 parametersΔρmin = 0.32 e Å3
0 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 constraintsExtinction coefficient: 0.08 (2)
Primary atom site location: structure-invariant direct methods
Crystal data top
C7H6F3NO2V = 814.1 (2) Å3
Mr = 193.13Z = 4
Monoclinic, C2/mMo Kα radiation
a = 16.643 (2) ŵ = 0.16 mm1
b = 7.1118 (10) ÅT = 293 K
c = 6.9618 (11) Å0.24 × 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)
Tmin = 0.963, Tmax = 0.969Rint = 0.076
3752 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0650 restraints
wR(F2) = 0.180H atoms treated by a mixture of independent and constrained refinement
S = 1.09Δρmax = 0.37 e Å3
707 reflectionsΔρmin = 0.32 e Å3
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
xyzUiso*/UeqOcc. (<1)
H0.275 (3)0.00000.341 (8)0.073 (13)*
C10.0515 (2)0.00000.2701 (6)0.0765 (12)
H1A0.04560.12540.31710.115*0.50
H1B0.07010.08160.37770.115*0.50
H1C0.00000.04380.20420.115*0.50
C20.18890 (17)0.00000.2149 (4)0.0436 (9)
C30.24211 (16)0.00000.0673 (4)0.0391 (8)
C40.21641 (19)0.00000.1280 (4)0.0480 (8)
H40.16250.00000.18810.058*
C50.3504 (2)0.00000.0863 (5)0.0563 (10)
H50.40340.00000.11370.068*
C60.32889 (16)0.00000.0952 (4)0.0443 (8)
C70.38690 (18)0.00000.2762 (5)0.0544 (9)
F10.46353 (14)0.00000.2439 (4)0.1048 (12)
F20.38017 (10)0.1475 (2)0.3904 (2)0.0853 (8)
N0.28189 (18)0.00000.2200 (5)0.0587 (9)
O10.20994 (15)0.00000.3872 (3)0.0718 (9)
O20.11034 (12)0.00000.1358 (3)0.0586 (8)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.057 (2)0.116 (3)0.058 (3)0.0000.0154 (17)0.000
C20.0503 (16)0.0517 (15)0.026 (2)0.0000.0038 (11)0.000
C30.0478 (15)0.0422 (13)0.0235 (19)0.0000.0066 (11)0.000
C40.0574 (17)0.0589 (16)0.0237 (19)0.0000.0065 (12)0.000
C50.0570 (17)0.0708 (19)0.042 (2)0.0000.0092 (14)0.000
C60.0491 (16)0.0483 (14)0.0331 (18)0.0000.0007 (11)0.000
C70.0481 (16)0.0667 (17)0.045 (2)0.0000.0052 (13)0.000
F10.0486 (13)0.185 (3)0.076 (2)0.0000.0056 (11)0.000
F20.0959 (13)0.0903 (13)0.0570 (14)0.0019 (7)0.0278 (8)0.0240 (7)
N0.077 (2)0.0781 (18)0.020 (2)0.0000.0034 (13)0.000
O10.0645 (15)0.125 (2)0.0230 (17)0.0000.0013 (10)0.000
O20.0470 (13)0.0914 (16)0.0352 (16)0.0000.0006 (9)0.000
Geometric parameters (Å, º) top
C1—O21.455 (4)C4—H40.9300
C1—H1A0.9600C5—N1.356 (5)
C1—H1B0.9600C5—C61.366 (5)
C1—H1C0.9600C5—H50.9300
C2—O11.196 (4)C6—C71.464 (5)
C2—O21.338 (4)C7—F11.329 (4)
C2—C31.457 (4)C7—F2i1.332 (3)
C3—C41.360 (4)C7—F21.332 (3)
C3—C61.427 (4)N—H0.84 (5)
C4—N1.347 (4)
O2—C1—H1A109.5N—C5—H5125.6
O2—C1—H1B109.5C6—C5—H5125.6
H1A—C1—H1B109.5C5—C6—C3106.2 (3)
O2—C1—H1C109.5C5—C6—C7124.3 (3)
H1A—C1—H1C109.5C3—C6—C7129.5 (3)
H1B—C1—H1C109.5F1—C7—F2i105.81 (19)
O1—C2—O2121.9 (3)F1—C7—F2105.81 (19)
O1—C2—C3126.3 (3)F2i—C7—F2104.0 (3)
O2—C2—C3111.8 (3)F1—C7—C6112.2 (3)
C4—C3—C6106.9 (3)F2i—C7—C6114.12 (17)
C4—C3—C2125.0 (3)F2—C7—C6114.12 (17)
C6—C3—C2128.1 (3)C4—N—C5109.3 (3)
N—C4—C3108.8 (3)C4—N—H119 (3)
N—C4—H4125.6C5—N—H131 (3)
C3—C4—H4125.6C2—O2—C1116.6 (3)
N—C5—C6108.8 (3)
Symmetry code: (i) x, y, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N—H···O1ii0.83 (6)2.03 (5)2.810 (4)156
C5—H5···F1iii0.932.523.442 (4)171
Symmetry codes: (ii) x, y, z1; (iii) x+1, y, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N—H···O1i0.83 (6)2.03 (5)2.810 (4)156
C5—H5···F1ii0.932.523.442 (4)171
Symmetry codes: (i) x, y, z1; (ii) x+1, y, z.
 

Acknowledgements

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

References

First citationBruker (2009). APEX2, SADABS and SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationBurnham, B. S., Gupton, J. T., Krumpe, K. E., Webb, T., Shuford, J., Bowers, B., Warren, A. E., Barnes, C. & Hall, I. H. (1998). Arch. Pharm. Pharm. Med. Chem. 331, 337–341.  CrossRef CAS
First citationDannhardt, G., Kiefer, W., Kramer, G., Maehrlein, S., Nowe, U. & Fiebich, B. (2000). Eur. J. Med. Chem. 35, 499–510.  Web of Science CrossRef PubMed CAS
First citationKrowicki, K., Jan Balzarini, T., Clercq, E. D., Robert, A., Newman, J. & Lawn, J. W. (1988). J. Med. Chem. 31, 341–345.  CrossRef CAS PubMed Web of Science
First citationMacrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.  Web of Science CrossRef CAS IUCr Journals
First citationMuchowski, J. M., Unger, S. H., Ackrell, J., Cheung, P., Cook, J., Gallegra, P., Halpern, O., Koehler, R. & Kluge, A. F. (1985). J. Med. Chem. 28, 1037–1049.  CrossRef CAS PubMed Web of Science
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationToja, E., Depaoli, A., Tuan, G. & Kettenring, J. (1987). Synthesis, pp. 272–274.  CrossRef

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