Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536805040092/ci6710sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536805040092/ci6710Isup2.hkl |
CCDC reference: 296534
A mixture of p-methylacetophenone (4.64 g, 35 mmol) and indole-3-aldehyde (2.00 g, 14 mmol) in MeOH (50 ml) was stirred and then 60% KOH aqueous solution (17 ml) was added dropwise at 298 K. The mixture was stirred for 42 h at 323–333 K and then cooled to room temperature and poured on water. The resulting precipitate was purified by preparative thin-layer chromatography (CH2Cl2/MeOH 18:1 as eluant) to give a yellow powder product, E-1-(3'-indolyl)-3-(4'-methyl)phenyl-1-propenone (0.593 g, m.p. 430–431 K, yield 16.5%). A mixture of E-1-(3'-indolyl)-3-(4'-methyl)phenyl-1-propenone (0.25 g, 1 mmol) and oxammonium hydrochloride (0.17 g, 2.5 mmol) in EtOH (30 ml) was stirred, and NaOH (0.04 mg, 1 mmol) and water (8 drops) were added. The mixture was refluxed for 42 h and then cooled to 298 K. The mixture was filtered, the filtrate was dried under pressure and the obtained solid was crystallized from EtOH to give a solid product (yield 54.3%). Single crystals of the title compound, suitable for X-ray diffraction study, were obtained by slow evaporation of a methanol solution (m.p. 440–442 K). 1H NMR (CDCl 3 , p.p.m.): 2.39 (s, 3H), 6.02 (dd, 1H, 1J = 9.03 Hz, 2J = 10.71 Hz), 3.52 (dd, 1H, 1J = 10.86 Hz, 2J = 16.56 Hz), 3.76 (dd, 1H, 1J = 10.86 Hz, 2J = 16.60 Hz), 7.09–7.64 (m, 9H), 8.15 (br s, 1H).
Atom H1A was located in a difference map and refined isotropically. The other H atoms were positioned geometrically (C—H = 0.93–0.97 Å) and constrained to ride on their parent atoms, with Uiso(H) values of 1.5Ueq(carrier atom) for methyl and 1.2Ueq(C) for the remaining H atoms. The methyl group was allowed to rotate freely about the C—C bond. In the absence of significant anomalous dispersion effects, Friedel pairs were merged before the final refinement.
Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL.
Fig. 1. A view of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. |
C18H16N2O | Dx = 1.238 Mg m−3 |
Mr = 276.33 | Melting point: 441 K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 1772 reflections |
a = 8.1881 (19) Å | θ = 2.9–21.2° |
b = 12.713 (3) Å | µ = 0.08 mm−1 |
c = 14.239 (3) Å | T = 294 K |
V = 1482.3 (6) Å3 | Block, purple |
Z = 4 | 0.30 × 0.24 × 0.12 mm |
F(000) = 584 |
Bruker SMART CCD area-detector diffractometer | 1747 independent reflections |
Radiation source: fine-focus sealed tube | 1120 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.050 |
ϕ and ω scans | θmax = 26.4°, θmin = 2.2° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −9→10 |
Tmin = 0.968, Tmax = 0.991 | k = −12→15 |
8368 measured reflections | l = −17→15 |
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)] = 0.039 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.093 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0374P)2 + 0.1511P] where P = (Fo2 + 2Fc2)/3 |
1747 reflections | (Δ/σ)max = 0.001 |
195 parameters | Δρmax = 0.11 e Å−3 |
0 restraints | Δρmin = −0.13 e Å−3 |
C18H16N2O | V = 1482.3 (6) Å3 |
Mr = 276.33 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 8.1881 (19) Å | µ = 0.08 mm−1 |
b = 12.713 (3) Å | T = 294 K |
c = 14.239 (3) Å | 0.30 × 0.24 × 0.12 mm |
Bruker SMART CCD area-detector diffractometer | 1747 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 1120 reflections with I > 2σ(I) |
Tmin = 0.968, Tmax = 0.991 | Rint = 0.050 |
8368 measured reflections |
R[F2 > 2σ(F2)] = 0.039 | 0 restraints |
wR(F2) = 0.093 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.02 | Δρmax = 0.11 e Å−3 |
1747 reflections | Δρmin = −0.13 e Å−3 |
195 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 1.0214 (3) | −0.03619 (14) | 0.58725 (13) | 0.0585 (6) | |
N1 | 0.7346 (4) | −0.2791 (2) | 0.4315 (2) | 0.0720 (9) | |
H1A | 0.686 (6) | −0.335 (3) | 0.424 (3) | 0.125 (17)* | |
N2 | 1.0613 (3) | 0.06924 (18) | 0.61107 (15) | 0.0537 (6) | |
C1 | 0.8258 (4) | −0.1266 (2) | 0.4900 (2) | 0.0512 (7) | |
C2 | 0.8890 (3) | −0.1382 (2) | 0.39596 (19) | 0.0506 (7) | |
C3 | 0.9899 (4) | −0.0790 (3) | 0.3374 (2) | 0.0676 (9) | |
H3 | 1.0326 | −0.0151 | 0.3577 | 0.081* | |
C4 | 1.0255 (5) | −0.1167 (3) | 0.2486 (2) | 0.0878 (11) | |
H4 | 1.0924 | −0.0774 | 0.2092 | 0.105* | |
C5 | 0.9634 (5) | −0.2120 (4) | 0.2172 (3) | 0.0971 (13) | |
H5 | 0.9896 | −0.2352 | 0.1571 | 0.117* | |
C6 | 0.8643 (5) | −0.2726 (3) | 0.2727 (3) | 0.0831 (11) | |
H6 | 0.8230 | −0.3366 | 0.2517 | 0.100* | |
C7 | 0.8282 (4) | −0.2347 (2) | 0.3618 (2) | 0.0603 (9) | |
C8 | 0.7342 (4) | −0.2139 (2) | 0.5070 (3) | 0.0670 (9) | |
H8 | 0.6787 | −0.2270 | 0.5628 | 0.080* | |
C9 | 0.8496 (4) | −0.0396 (2) | 0.5576 (2) | 0.0573 (8) | |
H9 | 0.7820 | −0.0536 | 0.6130 | 0.069* | |
C10 | 0.8191 (4) | 0.0732 (2) | 0.5261 (2) | 0.0588 (8) | |
H10A | 0.8329 | 0.0812 | 0.4588 | 0.071* | |
H10B | 0.7110 | 0.0973 | 0.5439 | 0.071* | |
C11 | 0.9497 (4) | 0.1296 (2) | 0.57947 (17) | 0.0465 (6) | |
C12 | 0.9562 (4) | 0.2435 (2) | 0.59429 (17) | 0.0459 (7) | |
C13 | 1.0595 (4) | 0.2882 (2) | 0.66125 (19) | 0.0539 (7) | |
H13 | 1.1280 | 0.2452 | 0.6965 | 0.065* | |
C14 | 1.0607 (4) | 0.3958 (2) | 0.67571 (19) | 0.0579 (8) | |
H14 | 1.1309 | 0.4240 | 0.7204 | 0.070* | |
C15 | 0.9599 (4) | 0.4624 (2) | 0.62517 (19) | 0.0519 (7) | |
C16 | 0.8611 (4) | 0.4184 (2) | 0.5577 (2) | 0.0574 (8) | |
H16 | 0.7948 | 0.4617 | 0.5214 | 0.069* | |
C17 | 0.8587 (4) | 0.3108 (2) | 0.54274 (19) | 0.0533 (7) | |
H17 | 0.7899 | 0.2832 | 0.4970 | 0.064* | |
C18 | 0.9587 (4) | 0.5789 (2) | 0.6439 (2) | 0.0702 (9) | |
H18A | 0.9517 | 0.6162 | 0.5854 | 0.105* | |
H18B | 1.0574 | 0.5984 | 0.6758 | 0.105* | |
H18C | 0.8663 | 0.5963 | 0.6823 | 0.105* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0610 (13) | 0.0443 (11) | 0.0703 (13) | 0.0098 (10) | −0.0141 (11) | −0.0086 (10) |
N1 | 0.071 (2) | 0.0399 (15) | 0.105 (2) | −0.0066 (15) | −0.0145 (18) | −0.0076 (17) |
N2 | 0.0581 (16) | 0.0495 (15) | 0.0536 (13) | 0.0066 (13) | −0.0051 (13) | −0.0096 (11) |
C1 | 0.0511 (18) | 0.0375 (16) | 0.0651 (18) | −0.0016 (14) | −0.0046 (15) | 0.0014 (15) |
C2 | 0.0450 (16) | 0.0459 (16) | 0.0611 (17) | −0.0019 (14) | −0.0081 (14) | −0.0055 (15) |
C3 | 0.056 (2) | 0.074 (2) | 0.072 (2) | −0.0112 (18) | −0.0038 (17) | −0.0008 (19) |
C4 | 0.071 (3) | 0.126 (3) | 0.067 (2) | −0.008 (3) | 0.0053 (19) | −0.002 (2) |
C5 | 0.076 (3) | 0.139 (4) | 0.076 (2) | 0.012 (3) | −0.005 (2) | −0.032 (3) |
C6 | 0.071 (2) | 0.081 (3) | 0.096 (3) | 0.015 (2) | −0.024 (2) | −0.043 (2) |
C7 | 0.0524 (19) | 0.0495 (19) | 0.079 (2) | 0.0024 (16) | −0.0130 (18) | −0.0109 (17) |
C8 | 0.072 (2) | 0.0520 (19) | 0.077 (2) | −0.0011 (18) | 0.0023 (18) | 0.0069 (19) |
C9 | 0.0527 (19) | 0.0526 (18) | 0.0667 (19) | 0.0008 (15) | 0.0005 (16) | −0.0039 (16) |
C10 | 0.0540 (19) | 0.0516 (18) | 0.0708 (19) | 0.0048 (16) | −0.0092 (16) | −0.0135 (16) |
C11 | 0.0431 (15) | 0.0491 (16) | 0.0474 (15) | 0.0046 (15) | −0.0002 (14) | −0.0055 (13) |
C12 | 0.0447 (16) | 0.0479 (16) | 0.0451 (14) | 0.0029 (14) | 0.0016 (15) | −0.0047 (13) |
C13 | 0.0591 (18) | 0.0523 (18) | 0.0503 (15) | −0.0005 (16) | −0.0043 (16) | −0.0001 (14) |
C14 | 0.065 (2) | 0.0589 (19) | 0.0501 (16) | −0.0112 (17) | −0.0004 (16) | −0.0085 (15) |
C15 | 0.0539 (18) | 0.0484 (17) | 0.0533 (16) | −0.0012 (16) | 0.0079 (16) | −0.0023 (14) |
C16 | 0.0563 (19) | 0.0533 (19) | 0.0626 (18) | 0.0111 (16) | −0.0048 (16) | −0.0018 (15) |
C17 | 0.0501 (18) | 0.0534 (18) | 0.0563 (17) | 0.0065 (15) | −0.0087 (15) | −0.0090 (15) |
C18 | 0.077 (2) | 0.0535 (19) | 0.080 (2) | −0.0043 (19) | 0.008 (2) | −0.0075 (16) |
O1—N2 | 1.421 (3) | C9—C10 | 1.524 (4) |
O1—C9 | 1.469 (4) | C9—H9 | 0.98 |
N1—C8 | 1.358 (4) | C10—C11 | 1.495 (4) |
N1—C7 | 1.375 (4) | C10—H10A | 0.97 |
N1—H1A | 0.82 (4) | C10—H10B | 0.97 |
N2—C11 | 1.275 (3) | C11—C12 | 1.464 (3) |
C1—C8 | 1.361 (4) | C12—C17 | 1.382 (3) |
C1—C2 | 1.443 (4) | C12—C13 | 1.395 (4) |
C1—C9 | 1.479 (4) | C13—C14 | 1.383 (4) |
C2—C3 | 1.395 (4) | C13—H13 | 0.93 |
C2—C7 | 1.410 (4) | C14—C15 | 1.384 (4) |
C3—C4 | 1.383 (5) | C14—H14 | 0.93 |
C3—H3 | 0.93 | C15—C16 | 1.375 (4) |
C4—C5 | 1.388 (5) | C15—C18 | 1.505 (4) |
C4—H4 | 0.93 | C16—C17 | 1.385 (4) |
C5—C6 | 1.370 (5) | C16—H16 | 0.93 |
C5—H5 | 0.93 | C17—H17 | 0.93 |
C6—C7 | 1.389 (4) | C18—H18A | 0.96 |
C6—H6 | 0.93 | C18—H18B | 0.96 |
C8—H8 | 0.93 | C18—H18C | 0.96 |
N2—O1—C9 | 108.48 (19) | C10—C9—H9 | 108.3 |
C8—N1—C7 | 108.7 (3) | C11—C10—C9 | 100.6 (2) |
C8—N1—H1A | 129 (3) | C11—C10—H10A | 111.7 |
C7—N1—H1A | 122 (3) | C9—C10—H10A | 111.7 |
C11—N2—O1 | 108.6 (2) | C11—C10—H10B | 111.7 |
C8—C1—C2 | 106.2 (3) | C9—C10—H10B | 111.7 |
C8—C1—C9 | 124.5 (3) | H10A—C10—H10B | 109.4 |
C2—C1—C9 | 129.3 (3) | N2—C11—C12 | 121.2 (3) |
C3—C2—C7 | 118.2 (3) | N2—C11—C10 | 113.8 (2) |
C3—C2—C1 | 135.4 (3) | C12—C11—C10 | 125.0 (3) |
C7—C2—C1 | 106.4 (3) | C17—C12—C13 | 117.5 (2) |
C4—C3—C2 | 119.0 (3) | C17—C12—C11 | 121.0 (2) |
C4—C3—H3 | 120.5 | C13—C12—C11 | 121.5 (2) |
C2—C3—H3 | 120.5 | C14—C13—C12 | 120.6 (3) |
C3—C4—C5 | 121.3 (3) | C14—C13—H13 | 119.7 |
C3—C4—H4 | 119.3 | C12—C13—H13 | 119.7 |
C5—C4—H4 | 119.3 | C13—C14—C15 | 121.5 (3) |
C6—C5—C4 | 121.5 (4) | C13—C14—H14 | 119.2 |
C6—C5—H5 | 119.3 | C15—C14—H14 | 119.2 |
C4—C5—H5 | 119.3 | C16—C15—C14 | 117.8 (3) |
C5—C6—C7 | 117.2 (3) | C16—C15—C18 | 121.3 (3) |
C5—C6—H6 | 121.4 | C14—C15—C18 | 120.9 (3) |
C7—C6—H6 | 121.4 | C15—C16—C17 | 121.1 (3) |
N1—C7—C6 | 129.4 (3) | C15—C16—H16 | 119.4 |
N1—C7—C2 | 107.8 (3) | C17—C16—H16 | 119.4 |
C6—C7—C2 | 122.8 (3) | C12—C17—C16 | 121.5 (3) |
N1—C8—C1 | 110.9 (3) | C12—C17—H17 | 119.3 |
N1—C8—H8 | 124.6 | C16—C17—H17 | 119.3 |
C1—C8—H8 | 124.6 | C15—C18—H18A | 109.5 |
O1—C9—C1 | 109.6 (2) | C15—C18—H18B | 109.5 |
O1—C9—C10 | 102.3 (2) | H18A—C18—H18B | 109.5 |
C1—C9—C10 | 119.4 (2) | C15—C18—H18C | 109.5 |
O1—C9—H9 | 108.3 | H18A—C18—H18C | 109.5 |
C1—C9—H9 | 108.3 | H18B—C18—H18C | 109.5 |
C9—O1—N2—C11 | −14.5 (3) | C2—C1—C9—O1 | −66.9 (4) |
C8—C1—C2—C3 | −179.3 (3) | C8—C1—C9—C10 | −128.9 (3) |
C9—C1—C2—C3 | 1.1 (6) | C2—C1—C9—C10 | 50.6 (4) |
C8—C1—C2—C7 | 0.3 (3) | O1—C9—C10—C11 | −22.9 (3) |
C9—C1—C2—C7 | −179.3 (3) | C1—C9—C10—C11 | −144.1 (3) |
C7—C2—C3—C4 | 0.3 (4) | O1—N2—C11—C12 | 179.2 (2) |
C1—C2—C3—C4 | 179.8 (3) | O1—N2—C11—C10 | −2.0 (3) |
C2—C3—C4—C5 | −0.2 (5) | C9—C10—C11—N2 | 16.5 (3) |
C3—C4—C5—C6 | 0.0 (6) | C9—C10—C11—C12 | −164.8 (2) |
C4—C5—C6—C7 | 0.2 (5) | N2—C11—C12—C17 | 164.8 (3) |
C8—N1—C7—C6 | 179.7 (3) | C10—C11—C12—C17 | −13.8 (4) |
C8—N1—C7—C2 | 0.4 (4) | N2—C11—C12—C13 | −15.8 (4) |
C5—C6—C7—N1 | −179.3 (3) | C10—C11—C12—C13 | 165.5 (3) |
C5—C6—C7—C2 | −0.1 (5) | C17—C12—C13—C14 | 1.0 (4) |
C3—C2—C7—N1 | 179.2 (3) | C11—C12—C13—C14 | −178.4 (3) |
C1—C2—C7—N1 | −0.4 (3) | C12—C13—C14—C15 | 0.4 (4) |
C3—C2—C7—C6 | −0.1 (4) | C13—C14—C15—C16 | −1.9 (4) |
C1—C2—C7—C6 | −179.8 (3) | C13—C14—C15—C18 | 178.0 (3) |
C7—N1—C8—C1 | −0.2 (4) | C14—C15—C16—C17 | 2.0 (4) |
C2—C1—C8—N1 | 0.0 (4) | C18—C15—C16—C17 | −177.9 (3) |
C9—C1—C8—N1 | 179.6 (3) | C13—C12—C17—C16 | −0.9 (4) |
N2—O1—C9—C1 | 151.5 (2) | C11—C12—C17—C16 | 178.5 (3) |
N2—O1—C9—C10 | 23.8 (3) | C15—C16—C17—C12 | −0.6 (5) |
C8—C1—C9—O1 | 113.6 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···O1i | 0.82 (4) | 2.13 (4) | 2.937 (4) | 170 (5) |
Symmetry code: (i) x−1/2, −y−1/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C18H16N2O |
Mr | 276.33 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 294 |
a, b, c (Å) | 8.1881 (19), 12.713 (3), 14.239 (3) |
V (Å3) | 1482.3 (6) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.30 × 0.24 × 0.12 |
Data collection | |
Diffractometer | Bruker SMART CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.968, 0.991 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8368, 1747, 1120 |
Rint | 0.050 |
(sin θ/λ)max (Å−1) | 0.626 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.039, 0.093, 1.02 |
No. of reflections | 1747 |
No. of parameters | 195 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.11, −0.13 |
Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SAINT, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997), SHELXTL.
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···O1i | 0.82 (4) | 2.13 (4) | 2.937 (4) | 170 (5) |
Symmetry code: (i) x−1/2, −y−1/2, −z+1. |
Indole skeletons play an important role as an intermediate for the design of many pharmacologically active compounds (Sundberg, 1996). Indole derivatives have been widely studied because of their biological activities, such as anti-inflammatory, antibacterial response etc. Isoxazole compounds demonstrate antiproliferative activity on tumor cells of different lineages and are able to induce erythroid differentiation and adipogenic conversion (Simoni et al., 1991). Isoxazoline derivatives act as inhibitors of Human Leukocyte Elastase (HLE) and cathepsin G (Cath G) (William et al., 1995). In view of these potential uses, we have recently focused our attention on the preparation of isoxazoline derivatives, using chalcone synthons (Darid et al., 1998). The title compound, (I), was synthesized by the cyclocondensation of 1–3'-indolyl-3-(4'-methyl)-phenyl-1-propene-3-one in the presence of oxammonium hydrochloride. An X-ray crystal structure determination of (I) was carried out to elucidate the structure, and the results are presented here.
In compound (I), the indole ring system is essentially planar (Fig. 1). The isoxazoline ring adopts an envelope conformation. Atom C9 deviates from the O1/N2/C10/C11 plane by 0.385 (4) Å. The N1/C1–C8 and C12–C17 planes form dihedral angles of 86.3 (1) and 14.8 (2)°, respectively, with the O1/N2/C10/C11 plane. Symmetry-related molecules are linked via N—H···O hydrogen bonds (Table 1) into a chain along the a axis.