3-(3-Chloro­phen­yl)-1-(2-methyl­imidazo[1,2-a]pyridin-3-yl)prop-2-en-1-one

The title compound, C₁₇H₁₃ClN₂O, was synthesized from 1-(2-methyl­imidazo[1,2-a]pyridin-3-yl)ethanone and 3-chloro­benzaldehyde in ethanol. The dihedral angle between the imidazopyridine ring system and the benzene ring is 7.43 (1)°. In the solid state, mol­ecules form centrosymmetric R²₂(14) dimeric units via a non-classical C—H...O hydrogen bond. These dimers are arranged in zigzag fashion along the [010] direction.

Key indicators

• Single-crystal X-ray study
• T = 295 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.047
• wR factor = 0.091
• Data-to-parameter ratio = 13.7

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT029_ALERT_3_A _diffrn_measured_fraction_theta_full Low .......       0.94

Author Response: The data have been collected on kappa CCD area-detector diffractometer and processed using Denzo. The low value of diffrn_mesured_fraction_theta_full is due to the fact that the Denzo image processing package has problems with certain strong reflections. These are often excluded from the data set. However, it present no problem since the data/parameter ratio is superior to 10.

Alert level C
PLAT022_ALERT_3_C Ratio Unique / Expected Reflections too Low ....       0.93

   1 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   1 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Chalcones and their derivatives and imidazo[1,2-a]pyridine derivatives represent two important classes of compound in chemistry, biochemistry and pharmacology. They are the focus of increasing attention because of their potential bioactive profile.

Chalcones and their derivatives have been found to have beneficial biological properties such as anti-inflammatory, anticancer, antibacterial, antiviral, antiprotozoal, antifungal, antiherpes, antitubercular, anti-invasive activities and cytotoxicity, insecticidal, enzyme inhibitory properties (Dimmock et al., 1999; Opletalova & Sedivy, 1999; Lawrence et al., 2001; Mukherjee et al., 2001; Lin et al., 2002). They are also used as intermediates in the synthesis of flavonocols (Bruneton, 1999). Furthermore, it has been reported that several chalcone derivatives present non-linear optical (NLO) properties (Goto et al., 1991; Sarojini et al., 2006).

As for imidazo[1,2-a]pyridine derivatives, they are important intermediates in the organic synthesis of therapeutic agents including anticonvulsant (Trapani et al., 2003) and antiviral (Gueiffier et al., 1998; Mavel et al., 2002) agents and are also used in clinical application as anxiolytics and hypnotics (Casacchia et al., 1989; Morton and Lader, 1992; Depoortere et al., 1986). For example, Zolpidem which contains the imidazo[1,2-a]pyridine ring system and better known as Stilnox® is the hypnosedative most prescribed in France (Giordanella, 2006). It is well known that while modifying the subtituents around the imidazopyridine nucleus, it is possible to obtain molecules having considerable biological properties. The title compound, highly functionalized, is a chalcone including an imidazo[1,2-a]pyridine ring system. This has been synthesized during a research project aimed at searching for new potential therapeutic uses of chalcones and eventually to improve their known properties.

The molecular structure of the title compound and its atomic numbering scheme are illustrated in Fig. 1. The values of bond lengths and angles in the molecule are comparable to those obtained in recent studies of imidazo[1,2-a]pyridine derivatives (Zhang and Hu, 2005; Duan et al., 2006). The imidazopyridine ring system is essentially planar, as usually observed, with a maximum deviation of 0.0095 (2) Å for atom C15. This ring system and the benzene ring form a dihedral angle of 7.43 (1)°. The ketone group (C7/C8/C9/O1) is almost planar, with a maximum deviation of 0.0392 (2) Å for C9 from the mean plane. In the benzene ring, bond lengths and angles are within normal ranges (Allen et al.,1987). In the three-dimensional crystal packing, carbon atom C5 in molecule at (x,y,z) acts as a hydrogen-bond donor via H5 to carbonyl atom O1 in the molecule at (-x + 2,-y + 1,-z + 1), thus forming a centrosymmetric R²₂(14) (Bernstein et al., 1995) dimeric unit (Fig. 2). These centrosymmetric R²₂(14) dimers are arranged in zigzag fashion along the [010] direction (Fig. 3).

Related literature

For related crystal structures, see: Zhang and Hu (2005); Duan et al. (2006). For properties of chalcones, see: Dimmock et al.(1999); Opletalova & Sedivy (1999); Lawrence et al. (2001); Mukherjee et al. (2001); Lin et al. (2002); Bruneton, (1999); Goto et al., (1991); Sarojini et al. (2006). For properties of imidazo[1,2-a]pyridine derivatives, see: Trapani et al. (2003); Gueiffier et al. (1998); Mavel et al. (2002); Casacchia et al.(1989); Morton & Lader (1992); Depoortere et al. (1986). For related literature, see: Allen et al. (1987); Bernstein et al. (1995); Giordanella (2006). For the refinement weighting scheme, see: Watkin (1994); Prince (1982).

S2. Experimental

10 ml of NaOH (20%) were added to a cold solution of ethanol (20 ml) and 1-(2-methylimidazo[1,2-a]pyridin-3-yl) ethanone (1 g, 5.8 mmol). After 5 minutes of cold agitation, 3-chlorobenzaldehyde (7 mmol) were added in small quantities. The mixture was stirred at ambient temperature for 3 h. 100 ml of water were added to this suspension. The resulting mixture was neutralized with acetic acid (20%). The precipitate was then filtered, washed many times with water, dried and recrystallized from a mixture of hexane/DCM (3:1). Yellow acicular single crystals of the title compound were obtained for X-ray diffraction analysis (yield: 75%; m.p.: 457 K).

¹H (DMSO-d₆) δ:2.83 (s, 3H); 7.20 (t, 1H, arom); 7.50 (m, 2H, H vinyl + Harom.); 7.65 (m, 2H, H vinyl + Harom.); 7.80 (m, 2H, H arom.); 7.90 (m, 2H, H arom.); 9.70 (d, 1H, H arom.). ¹³C (DMSO-d₆) δ:18.10 (C, CH3); 110 (C arom.); 118 (2 C arom.); 120 (C arom.); 124 (C arom.); 126 (C vinyl); 128 (2 C arom.); 130 (2 C arom.); 135 (C—Cl); 138 (C arom.); 140 (C arom.); 146 (C vinyl); 152 (C arom.); 179 (C=O). TOF+, SM: 296; m/z(%): M+1= 297 (35), 296 (100), 268 (47), 185 (77), 132 (53), 90 (38), 78 (58), 51 (42).

S3. Refinement

The H atoms were all located in a difference Fourier map. They were all initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.99 Å and U_iso(H) in the range 1.2–1.5 times U_eq of the parent atom), after which their positions were refined with riding constraints.

Computing details

Data collection: COLLECT (Nonius, 1997); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: ORTEP-3 (Farrugia, 1997) and PLATON (Spek, 2003); software used to prepare material for publication: CRYSTALS.

Figures

	Fig. 1. The molecular structure of the title compound and the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius.
	Fig. 2. Part of the crystal structure, showing the formation of a centrosymmetric R^22(14) dimer. For the sake of clarity, the unit-cell outline has omitted. Dashed lines indicate C—H···O hydrogen bonds. Atom O1a belongs to the molecule at symmetry position (-x + 2,-y + 1,-z + 1).
	Fig. 3. Crystal packing of the title compound, viewed down the c axis, showing centrosymmetric R^22(14) dimers arranged in a zigzag fashion along the b axis. H atoms not involved in hydrogen bonds have been omitted for clarity. Dashed lines indicate C—H···O hydrogen bonds.

3-(3-Chlorophenyl)-1-(2-methylimidazo[1,2-a]pyridin-3-yl)prop-2-en-1-one

Crystal data

C17H13ClN2O	F(000) = 616
Mr = 296.76	Dx = 1.382 Mg m^−3
Monoclinic, P21/n	Melting point: 457 K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71070 Å
a = 4.784 (2) Å	Cell parameters from 9741 reflections
b = 21.690 (2) Å	θ = 1.8–26.0°
c = 13.773 (9) Å	µ = 0.27 mm^−1
β = 93.425 (4)°	T = 295 K
V = 1426.6 (11) Å^3	Needle, yellow
Z = 4	0.55 × 0.50 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer	2076 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.05
ϕ scans	θmax = 26.0°, θmin = 1.8°
Absorption correction: multi-scan DENZO/SCALEPACK (Otwinowski & Minor, 1997)	h = −5→5
Tmin = 0.90, Tmax = 0.95	k = −24→26
9741 measured reflections	l = −16→16
2608 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.047	H-atom parameters constrained
wR(F^2) = 0.091	Method, part 1, Chebychev polynomial, (Watkin, 1994, Prince, 1982) [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)^2]^2 Ai are: 211. 268. 175. 53.2
S = 0.88	(Δ/σ)max = 0.001
2608 reflections	Δρmax = 0.19 e Å^−3
190 parameters	Δρmin = −0.20 e Å^−3
0 restraints

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

	x	y	z	Uiso*/Ueq
Cl1	1.77966 (16)	0.56077 (4)	0.06407 (5)	0.0783
O1	0.8443 (4)	0.40641 (8)	0.44145 (11)	0.0596
N1	0.5302 (4)	0.31509 (7)	0.33536 (12)	0.0418
N2	0.4943 (4)	0.29997 (8)	0.17382 (13)	0.0512
C1	1.4942 (4)	0.52402 (9)	0.21641 (14)	0.0415
C2	1.6944 (4)	0.56347 (10)	0.18489 (15)	0.0442
C3	1.8321 (5)	0.60495 (10)	0.24604 (17)	0.0527
C4	1.7694 (5)	0.60653 (11)	0.34198 (18)	0.0554
C5	1.5692 (5)	0.56696 (10)	0.37618 (16)	0.0488
C6	1.4298 (4)	0.52513 (9)	0.31395 (14)	0.0381
C7	1.2198 (4)	0.48419 (10)	0.35239 (14)	0.0419
C8	1.0923 (4)	0.43741 (9)	0.30706 (14)	0.0428
C9	0.8804 (4)	0.40006 (9)	0.35401 (14)	0.0417
C10	0.7160 (4)	0.35647 (9)	0.29491 (14)	0.0387
C11	0.4667 (5)	0.30482 (10)	0.43006 (17)	0.0554
C12	0.2703 (6)	0.26144 (11)	0.4480 (2)	0.0666
C13	0.1361 (6)	0.22782 (11)	0.3726 (2)	0.0668
C14	0.1991 (5)	0.23756 (10)	0.2791 (2)	0.0591
C15	0.4012 (5)	0.28214 (9)	0.25937 (17)	0.0475
C16	0.6838 (4)	0.34500 (9)	0.19497 (15)	0.0434
C17	0.8231 (5)	0.37501 (11)	0.11281 (15)	0.0549
H5	1.5256	0.5682	0.4424	0.0574*
H8	1.1478	0.4266	0.2439	0.0522*
H4	1.8610	0.6348	0.3850	0.0640*
H7	1.1715	0.4923	0.4162	0.0505*
H1	1.4001	0.4976	0.1730	0.0487*
H14	0.1088	0.2156	0.2262	0.0709*
H3	1.9803	0.6298	0.2218	0.0636*
H11	0.5623	0.3271	0.4800	0.0676*
H12	0.2278	0.2543	0.5120	0.0808*
H13	−0.0031	0.1991	0.3867	0.0814*
H171	0.8229	0.4197	0.1193	0.0802*
H172	0.7273	0.3636	0.0530	0.0805*
H173	1.0211	0.3612	0.1109	0.0818*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0880 (5)	0.0987 (6)	0.0507 (4)	−0.0175 (4)	0.0246 (3)	0.0127 (3)
O1	0.0692 (12)	0.0695 (11)	0.0415 (8)	−0.0186 (8)	0.0148 (7)	−0.0005 (7)
N1	0.0425 (10)	0.0342 (8)	0.0500 (10)	0.0049 (7)	0.0135 (7)	0.0046 (7)
N2	0.0505 (12)	0.0480 (10)	0.0550 (11)	−0.0002 (8)	0.0029 (8)	−0.0014 (8)
C1	0.0365 (12)	0.0463 (11)	0.0419 (10)	−0.0009 (8)	0.0035 (8)	0.0004 (9)
C2	0.0404 (13)	0.0486 (12)	0.0444 (11)	0.0015 (9)	0.0078 (9)	0.0082 (9)
C3	0.0430 (14)	0.0449 (12)	0.0708 (15)	−0.0053 (10)	0.0074 (11)	0.0078 (11)
C4	0.0532 (15)	0.0464 (13)	0.0664 (15)	−0.0071 (10)	0.0008 (11)	−0.0095 (11)
C5	0.0508 (14)	0.0510 (12)	0.0449 (11)	0.0015 (10)	0.0061 (9)	−0.0057 (9)
C6	0.0331 (11)	0.0414 (10)	0.0400 (10)	0.0036 (8)	0.0039 (8)	0.0020 (8)
C7	0.0395 (12)	0.0496 (12)	0.0376 (10)	0.0040 (9)	0.0094 (8)	0.0032 (9)
C8	0.0405 (12)	0.0474 (11)	0.0414 (10)	0.0013 (9)	0.0106 (8)	0.0012 (9)
C9	0.0407 (13)	0.0423 (11)	0.0428 (11)	0.0050 (9)	0.0094 (8)	0.0040 (8)
C10	0.0388 (12)	0.0357 (10)	0.0426 (10)	0.0037 (8)	0.0118 (8)	0.0035 (8)
C11	0.0688 (16)	0.0437 (12)	0.0561 (13)	−0.0014 (11)	0.0243 (11)	0.0063 (10)
C12	0.080 (2)	0.0451 (13)	0.0779 (17)	−0.0036 (12)	0.0345 (14)	0.0106 (12)
C13	0.0590 (17)	0.0384 (12)	0.106 (2)	−0.0038 (11)	0.0255 (15)	0.0096 (13)
C14	0.0498 (15)	0.0388 (12)	0.0890 (18)	0.0002 (10)	0.0063 (12)	0.0028 (12)
C15	0.0424 (13)	0.0356 (11)	0.0650 (14)	0.0047 (9)	0.0058 (10)	0.0012 (10)
C16	0.0417 (12)	0.0410 (11)	0.0479 (11)	0.0072 (9)	0.0064 (8)	0.0021 (9)
C17	0.0624 (16)	0.0618 (14)	0.0413 (12)	−0.0014 (11)	0.0091 (10)	0.0040 (10)

Geometric parameters (Å, º)

Cl1—C2	1.738 (2)	C7—C8	1.321 (3)
O1—C9	1.234 (2)	C7—H7	0.939
N1—C10	1.402 (2)	C8—C9	1.477 (3)
N1—C11	1.375 (3)	C8—H8	0.954
N1—C15	1.382 (3)	C9—C10	1.448 (3)
N2—C15	1.341 (3)	C10—C16	1.398 (3)
N2—C16	1.353 (3)	C11—C12	1.363 (3)
C1—C2	1.374 (3)	C11—H11	0.936
C1—C6	1.396 (3)	C12—C13	1.394 (4)
C1—H1	0.926	C12—H12	0.930
C2—C3	1.373 (3)	C13—C14	1.355 (4)
C3—C4	1.373 (3)	C13—H13	0.941
C3—H3	0.967	C14—C15	1.406 (3)
C4—C5	1.389 (3)	C14—H14	0.952
C4—H4	0.942	C16—C17	1.496 (3)
C5—C6	1.391 (3)	C17—H171	0.973
C5—H5	0.948	C17—H172	0.951
C6—C7	1.463 (3)	C17—H173	0.995
C10—N1—C11	131.44 (19)	C8—C9—C10	118.41 (17)
C10—N1—C15	107.16 (17)	O1—C9—C10	121.23 (19)
C11—N1—C15	121.40 (19)	C9—C10—N1	122.03 (17)
C15—N2—C16	105.81 (19)	C9—C10—C16	133.92 (18)
C2—C1—C6	119.42 (19)	N1—C10—C16	104.01 (18)
C2—C1—H1	120.2	N1—C11—C12	118.5 (2)
C6—C1—H1	120.4	N1—C11—H11	119.2
Cl1—C2—C1	119.31 (17)	C12—C11—H11	122.3
Cl1—C2—C3	118.54 (17)	C11—C12—C13	121.2 (2)
C1—C2—C3	122.1 (2)	C11—C12—H12	118.7
C2—C3—C4	118.8 (2)	C13—C12—H12	120.2
C2—C3—H3	119.2	C12—C13—C14	120.5 (2)
C4—C3—H3	121.7	C12—C13—H13	119.5
C3—C4—C5	120.4 (2)	C14—C13—H13	120.0
C3—C4—H4	120.1	C13—C14—C15	119.1 (2)
C5—C4—H4	119.5	C13—C14—H14	122.1
C4—C5—C6	120.6 (2)	C15—C14—H14	118.8
C4—C5—H5	120.2	C14—C15—N1	119.4 (2)
C6—C5—H5	119.2	C14—C15—N2	129.6 (2)
C1—C6—C5	118.62 (19)	N1—C15—N2	111.09 (19)
C1—C6—C7	122.23 (18)	C10—C16—N2	111.93 (18)
C5—C6—C7	119.15 (18)	C10—C16—C17	129.7 (2)
C6—C7—C8	127.05 (18)	N2—C16—C17	118.32 (19)
C6—C7—H7	116.0	C16—C17—H171	111.1
C8—C7—H7	116.9	C16—C17—H172	109.2
C7—C8—C9	121.61 (19)	H171—C17—H172	109.6
C7—C8—H8	118.2	C16—C17—H173	110.9
C9—C8—H8	120.1	H171—C17—H173	108.0
C8—C9—O1	120.4 (2)	H172—C17—H173	108.0

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5···O1^i	0.95	2.52	3.339 (4)	145

Symmetry code: (i) −x+2, −y+1, −z+1.