(Z)-3-(1-Methyl-1H-indol-3-yl)-2-(thio­phen-3-yl)­acrylo­nitrile

The title compound, C₁₆H₁₂N₂S, has been synthesized by base-catalyzed condensation of 1-methyl­indole-3-carbox­aldehyde with thio­phene-3-aceto­nitrile. The product assumes an approx­imately planar Z configuration. The mol­ecule has a thienyl-ring flip disorder.

S1. Comment

There has been an increasing demand for new antituberculosis agents, as the fast development of mycobacterial resistance to conventional drugs is one of the major difficulties in the treatment of tuberculosis. Encouraged by the antitubercular activity of 3-aryl-substituted 2-[1H(2H)benzotriazol-1(2)-yl]acrylonitriles (Sanna et al., 2000), we have synthesized a series of substituted aryl/heteroaryl 2-thiophen-3-yl-acrylonitriles and evaluated them for antitubercular activity against Mycobacterium tuberculosis H37R_v. In the present paper, we present the results of an X-ray structural investigation of the title compound, (I), which was prepared by base catalyzed condensation of 1-methylindole-3-carboxaldehyde with thiophen-3-acetonitrile. The compound was initially identified by NMR spectroscopy. In order to confirm the geometry, and to obtain detailed information on the structural conformation of the molecule, its X-ray structure determination has been carried out, and the results are presented here.

Fig. 1 shows an ellipsoid plot of (I), and selected geometric parameters are presented in Table 1. In (I), the indole ring is in a trans disposition with respect to the thiophene, across the double bond linking the two rings. Deviations from the ideal bond-angle geometry around the sp² C atoms of the double bonds are observed. The C10—C11—C16 and C13—C12—C11 bond angles are 120.3 (2) and 121.1 (4)°, respectively, close to the ideal geometry (120°); the C2—C3—C10, C11—C10—C3, C10—C11—C12 and C16—C11—C12 angles [129.8 (2), 129.8 (2), 125.3 (2) and 114.4 (2)°, respectively] are distorted because of steric hindrance of the double? linking the two ring systems. The C3—C10, C11—C12 and C11—C16 bond lengths are slightly shorter [1.436 (3), 1.472 (3) and 1.435 (4) Å, respectively], providing evidence of some delocalization in the bridging units of this molecule (International Tables for Crystallography, 1992, Vol. C, Table 9.5.1.1.). The C2—C3—C10—C11, C10—C11—C12—C13, C3—C10—C11—C16 and C16—C11—C12—C13 torsion angles [−5.7 (4), 176.4 (9), 0.0 (4) and −1.3 (10)°] indicate that the indole and thiophene ring plane deviates little from the plane of the double bond. Furthermore, the conformation is stabilized by intramolecular C—H.·N and C—H..π interactions (Table 2). The molecule has a thienyl-ring flip disorder, the thiophene ring being disordered over two conformations about the C11—C12 bond, with a major:minor ratio of about 75:25.

The mode of packing of (I) along the a direction is illustrated in Fig. 2. Van der Waal's forces contribute to the stabilization of the crystal structure.

S2. Experimental

A mixture of 1-methylindole-3-carboxaldehyde (0.796 g, 5 mmol) and thiophene-3-acetonitrile (0.616 g, 5 mmol) was dissolved in 5% methanol sodium methoxide (15 ml) and the solution was refluxed for 2 h. The cooled reaction mixture was poured into crushed ice (100 g) and the yellow solid that separated was collected by filtration and dried. Crystallization from methanol afforded yellow needles, which were suitable for X-ray analysis. ¹H NMR (CDCl₃, p.p.m.): 3.87 (s, 3H), 7.25–7.39 (m, 5H), 7.45 (t, 1H), 7.73 (s, 1H), 7.75 (s, 1H), 8.24 (s, 1H); ¹³C NMR (CDCl₃, p.p.m.): 33.8, 99.8, 110.2, 110.4, 118.2, 120.2, 121.1, 121.2, 123.2, 124.2, 127.1, 128.1, 130.4, 132.0, 136.7, 137.1.

S3. Refinement

The geometric and displacement parameters of the atoms involved were restrained to be similar, approximately isotropic, and to obey the rigid-bond criterion. As such, the geometry should not be considered definitive.

Computing details

Data collection: COLLECT (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO–SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL (Sheldrick, 1995); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997) and local procedures.

Figures

	Fig. 1. A view of (I), with displacement ellipsoids drawn at the 50% probability level.
	Fig. 2. The crystal packing of (I), viewed along the a direction.

(Z)-3-(1-Methyl-1H-indol-3-yl)-2-(thiophen-3-yl)acrylonitrile

Crystal data

C16H12N2S	F(000) = 552
Mr = 264.34	Dx = 1.366 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 15.4031 (8) Å	Cell parameters from 2486 reflections
b = 5.8621 (4) Å	θ = 1.0–25.4°
c = 15.4902 (9) Å	µ = 0.24 mm^−1
β = 113.237 (3)°	T = 90 K
V = 1285.22 (13) Å^3	Splintered lath, yellow
Z = 4	0.40 × 0.10 × 0.05 mm

Data collection

Nonius KappaCCD diffractometer	2253 independent reflections
Radiation source: fine-focus sealed tube	1594 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.050
Detector resolution: 18 pixels mm^-1	θmax = 25.0°, θmin = 1.4°
ω scans at fixed χ = 55°	h = −18→18
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	k = −6→6
Tmin = 0.911, Tmax = 0.988	l = −18→18
4061 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.052	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.126	H-atom parameters constrained
S = 1.57	w = 1/[σ^2(Fo^2) + (0.0537P)^2 + 0.4997P] where P = (Fo^2 + 2Fc^2)/3
2253 reflections	(Δ/σ)max = 0.023
210 parameters	Δρmax = 0.23 e Å^−3
249 restraints	Δρmin = −0.31 e Å^−3

Special details

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.

The thiophene ring is disordered into two conformations about the C11—C12 bond, with major:minor ratio of about 75:25. The geometry of these pieces were made similar (SAME in SHELXL) and the displacement parameters of the atoms involved were restrained to be similar (SIMU), approximately isotropic (ISOR) and to obey the rigid bond criterion (DELU). As such, the geometry should not be considered definitive.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
N1	0.17821 (14)	0.4694 (4)	0.52307 (13)	0.0272 (5)
C1	0.10681 (17)	0.6189 (5)	0.45847 (17)	0.0319 (7)
H1A	0.0439	0.5652	0.4508	0.048*
H1B	0.1120	0.6179	0.3974	0.048*
H1C	0.1163	0.7745	0.4837	0.048*
C2	0.16214 (17)	0.2776 (5)	0.56377 (16)	0.0282 (6)
H2	0.1013	0.2251	0.5567	0.034*
C3	0.24576 (17)	0.1690 (4)	0.61668 (15)	0.0251 (6)
C4	0.31928 (17)	0.3060 (5)	0.60580 (15)	0.0251 (6)
C5	0.41763 (17)	0.2901 (5)	0.63978 (16)	0.0297 (6)
H5	0.4499	0.1676	0.6797	0.036*
C6	0.46720 (18)	0.4551 (5)	0.61448 (17)	0.0319 (7)
H6	0.5341	0.4452	0.6372	0.038*
C7	0.42025 (18)	0.6379 (5)	0.55556 (17)	0.0329 (7)
H7	0.4560	0.7489	0.5392	0.040*
C8	0.32334 (18)	0.6586 (5)	0.52122 (16)	0.0287 (6)
H8	0.2914	0.7819	0.4816	0.034*
C9	0.27420 (16)	0.4902 (4)	0.54735 (15)	0.0251 (6)
C10	0.26214 (17)	−0.0316 (4)	0.67420 (15)	0.0261 (6)
H10	0.3256	−0.0843	0.6998	0.031*
C11	0.20065 (17)	−0.1572 (4)	0.69753 (15)	0.0252 (6)
C12	0.22589 (17)	−0.3566 (4)	0.76036 (15)	0.0265 (6)	0.754 (3)
C13	0.1592 (6)	−0.466 (2)	0.7841 (11)	0.0279 (14)	0.754 (3)
H13	0.0946	−0.4230	0.7614	0.034*	0.754 (3)
S1	0.20622 (12)	−0.6902 (3)	0.85915 (15)	0.0296 (4)	0.754 (3)
C14	0.3142 (7)	−0.635 (2)	0.8613 (8)	0.042 (2)	0.754 (3)
H14	0.3688	−0.7202	0.8982	0.051*	0.754 (3)
C15	0.3163 (6)	−0.459 (2)	0.8056 (13)	0.0282 (12)	0.754 (3)
H15	0.3715	−0.4095	0.7977	0.034*	0.754 (3)
C12'	0.22589 (17)	−0.3566 (4)	0.76036 (15)	0.0265 (6)	0.246 (3)
C13'	0.3175 (18)	−0.438 (8)	0.801 (4)	0.029 (3)	0.246 (3)
H13'	0.3690	−0.3725	0.7910	0.035*	0.246 (3)
S1'	0.3282 (5)	−0.6688 (15)	0.8715 (6)	0.0288 (13)	0.246 (3)
C14'	0.2121 (14)	−0.650 (4)	0.851 (2)	0.036 (3)	0.246 (3)
H14'	0.1831	−0.7438	0.8825	0.043*	0.246 (3)
C15'	0.1644 (18)	−0.492 (7)	0.787 (3)	0.029 (3)	0.246 (3)
H15'	0.0978	−0.4730	0.7634	0.034*	0.246 (3)
C16	0.10273 (19)	−0.0946 (5)	0.66319 (16)	0.0291 (6)
N2	0.02315 (16)	−0.0550 (4)	0.63686 (15)	0.0404 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0328 (12)	0.0274 (13)	0.0253 (11)	0.0021 (11)	0.0159 (9)	0.0021 (10)
C1	0.0323 (15)	0.0351 (17)	0.0305 (14)	0.0091 (13)	0.0149 (12)	0.0059 (12)
C2	0.0309 (15)	0.0324 (16)	0.0255 (13)	−0.0021 (13)	0.0156 (12)	−0.0023 (12)
C3	0.0289 (14)	0.0277 (15)	0.0199 (12)	0.0003 (13)	0.0110 (11)	−0.0027 (11)
C4	0.0320 (14)	0.0256 (15)	0.0205 (12)	−0.0013 (13)	0.0134 (11)	−0.0020 (11)
C5	0.0315 (15)	0.0348 (16)	0.0233 (13)	−0.0004 (13)	0.0115 (11)	0.0007 (12)
C6	0.0283 (15)	0.0377 (18)	0.0304 (14)	−0.0030 (13)	0.0123 (12)	−0.0004 (13)
C7	0.0350 (15)	0.0368 (17)	0.0316 (14)	−0.0066 (14)	0.0180 (12)	0.0021 (13)
C8	0.0351 (15)	0.0291 (16)	0.0243 (13)	0.0024 (13)	0.0143 (11)	0.0011 (11)
C9	0.0276 (14)	0.0296 (15)	0.0218 (12)	−0.0006 (13)	0.0137 (11)	−0.0047 (12)
C10	0.0296 (14)	0.0299 (16)	0.0204 (12)	0.0026 (13)	0.0117 (11)	−0.0039 (11)
C11	0.0290 (13)	0.0290 (15)	0.0203 (12)	−0.0007 (12)	0.0124 (10)	−0.0032 (11)
C12	0.0338 (13)	0.0274 (14)	0.0211 (11)	0.0000 (11)	0.0139 (10)	−0.0046 (10)
C13	0.034 (2)	0.029 (3)	0.022 (2)	0.0015 (19)	0.0124 (19)	0.001 (2)
S1	0.0350 (6)	0.0300 (8)	0.0268 (6)	−0.0003 (5)	0.0153 (4)	0.0036 (5)
C14	0.044 (3)	0.042 (4)	0.037 (3)	0.007 (3)	0.012 (2)	−0.006 (3)
C15	0.035 (2)	0.027 (3)	0.027 (3)	−0.0015 (19)	0.0160 (16)	−0.001 (2)
C12'	0.0338 (13)	0.0274 (14)	0.0211 (11)	0.0000 (11)	0.0139 (10)	−0.0046 (10)
C13'	0.036 (4)	0.030 (5)	0.024 (4)	−0.001 (4)	0.014 (4)	0.001 (4)
S1'	0.030 (2)	0.032 (3)	0.027 (2)	0.0004 (19)	0.0151 (18)	−0.0012 (17)
C14'	0.041 (4)	0.037 (4)	0.031 (4)	−0.005 (4)	0.016 (3)	−0.004 (4)
C15'	0.032 (4)	0.032 (4)	0.027 (4)	−0.001 (4)	0.017 (3)	−0.005 (4)
C16	0.0362 (17)	0.0295 (16)	0.0246 (13)	−0.0003 (14)	0.0153 (12)	0.0042 (12)
N2	0.0369 (15)	0.0448 (16)	0.0427 (13)	0.0031 (13)	0.0193 (11)	0.0111 (12)

Geometric parameters (Å, º)

N1—C2	1.359 (3)	C10—C11	1.356 (3)
N1—C9	1.380 (3)	C10—H10	0.9500
N1—C1	1.453 (3)	C11—C16	1.435 (4)
C1—H1A	0.9800	C11—C12	1.472 (3)
C1—H1B	0.9800	C12—C13	1.379 (8)
C1—H1C	0.9800	C12—C15	1.421 (8)
C2—C3	1.379 (3)	C13—S1	1.712 (7)
C2—H2	0.9500	C13—H13	0.9500
C3—C10	1.436 (3)	S1—C14	1.682 (10)
C3—C4	1.451 (3)	C14—C15	1.355 (12)
C4—C5	1.397 (3)	C14—H14	0.9500
C4—C9	1.404 (3)	C15—H15	0.9500
C5—C6	1.382 (4)	C13'—S1'	1.702 (19)
C5—H5	0.9500	C13'—H13'	0.9500
C6—C7	1.408 (4)	S1'—C14'	1.693 (17)
C6—H6	0.9500	C14'—C15'	1.34 (2)
C7—C8	1.378 (3)	C14'—H14'	0.9500
C7—H7	0.9500	C15'—H15'	0.9500
C8—C9	1.398 (3)	C16—N2	1.152 (3)
C8—H8	0.9500
C2—N1—C9	108.6 (2)	N1—C9—C8	128.9 (2)
C2—N1—C1	126.3 (2)	N1—C9—C4	108.2 (2)
C9—N1—C1	125.0 (2)	C8—C9—C4	122.9 (2)
N1—C1—H1A	109.5	C11—C10—C3	129.8 (2)
N1—C1—H1B	109.5	C11—C10—H10	115.1
H1A—C1—H1B	109.5	C3—C10—H10	115.1
N1—C1—H1C	109.5	C10—C11—C16	120.3 (2)
H1A—C1—H1C	109.5	C10—C11—C12	125.3 (2)
H1B—C1—H1C	109.5	C16—C11—C12	114.4 (2)
N1—C2—C3	111.0 (2)	C13—C12—C15	111.1 (4)
N1—C2—H2	124.5	C13—C12—C11	121.1 (4)
C3—C2—H2	124.5	C15—C12—C11	127.8 (4)
C2—C3—C10	129.8 (2)	C12—C13—S1	112.2 (5)
C2—C3—C4	105.3 (2)	C12—C13—H13	123.9
C10—C3—C4	124.8 (2)	S1—C13—H13	123.9
C5—C4—C9	118.8 (2)	C14—S1—C13	91.0 (4)
C5—C4—C3	134.4 (2)	C15—C14—S1	113.9 (7)
C9—C4—C3	106.9 (2)	C15—C14—H14	123.0
C6—C5—C4	119.0 (2)	S1—C14—H14	123.0
C6—C5—H5	120.5	C14—C15—C12	111.7 (7)
C4—C5—H5	120.5	C14—C15—H15	124.1
C5—C6—C7	121.1 (2)	C12—C15—H15	124.1
C5—C6—H6	119.4	S1'—C13'—H13'	123.5
C7—C6—H6	119.4	C14'—S1'—C13'	90.1 (11)
C8—C7—C6	121.2 (2)	C15'—C14'—S1'	114.3 (16)
C8—C7—H7	119.4	C15'—C14'—H14'	122.9
C6—C7—H7	119.4	S1'—C14'—H14'	122.9
C7—C8—C9	117.0 (2)	C14'—C15'—H15'	124.2
C7—C8—H8	121.5	N2—C16—C11	176.6 (3)
C9—C8—H8	121.5
C9—N1—C2—C3	1.0 (3)	C5—C4—C9—C8	0.2 (3)
C1—N1—C2—C3	176.3 (2)	C3—C4—C9—C8	−179.9 (2)
N1—C2—C3—C10	177.1 (2)	C2—C3—C10—C11	−5.7 (4)
N1—C2—C3—C4	−1.0 (3)	C4—C3—C10—C11	172.0 (2)
C2—C3—C4—C5	−179.5 (3)	C3—C10—C11—C16	0.0 (4)
C10—C3—C4—C5	2.3 (4)	C3—C10—C11—C12	−177.6 (2)
C2—C3—C4—C9	0.6 (3)	C10—C11—C12—C13	176.4 (9)
C10—C3—C4—C9	−177.6 (2)	C16—C11—C12—C13	−1.3 (10)
C9—C4—C5—C6	−0.3 (3)	C10—C11—C12—C15	−2.0 (12)
C3—C4—C5—C6	179.9 (2)	C16—C11—C12—C15	−179.7 (12)
C4—C5—C6—C7	0.1 (4)	C15—C12—C13—S1	−0.4 (17)
C5—C6—C7—C8	0.1 (4)	C11—C12—C13—S1	−179.1 (6)
C6—C7—C8—C9	−0.2 (4)	C12—C13—S1—C14	1.2 (12)
C2—N1—C9—C8	179.3 (2)	C13—S1—C14—C15	−1.8 (15)
C1—N1—C9—C8	3.9 (4)	S1—C14—C15—C12	2 (2)
C2—N1—C9—C4	−0.5 (2)	C13—C12—C15—C14	−1 (2)
C1—N1—C9—C4	−175.9 (2)	C11—C12—C15—C14	177.7 (10)
C7—C8—C9—N1	−179.8 (2)	C13'—S1'—C14'—C15'	6 (5)
C7—C8—C9—C4	0.0 (3)	C10—C11—C16—N2	164 (4)
C5—C4—C9—N1	−179.9 (2)	C12—C11—C16—N2	−18 (4)
C3—C4—C9—N1	−0.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···C16	0.95	2.49	3.014 (4)	115
C2—H2···N2	0.95	2.62	3.403 (3)	140
C13—H13···C16	0.95	2.49	2.780 (8)	98