
Supporting information
![]() | Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536803011462/wn6158sup1.cif |
![]() | Structure factor file (CIF format) https://doi.org/10.1107/S1600536803011462/wn6158Isup2.hkl |
CCDC reference: 217612
A mixture of levulinic acid and o-chlorobenzaldehyde, containing HCl at room temperature, gave the phenylmethyllevulinic acid, which was treated with hydrazine in boiling ethanol to give 5-(o-chlorobenzylidene)-6-methylpyridazin-3-one. Addition of 2-bromoethanol, in the presence of potassium carbonate in boiling tetrahydrofuran, yielded 5-(2-chlorobenzyl)-2-(2-hydroxyethyl)-6-methylpyridazin-3(2H)-one. Single crystals were obtained by recrystallization from ethanol.
All H atoms were located in a difference Fourier synthesis and were refined with fixed individual displacement parameters [Uiso(H) = 1.2Ueq(C) or 1.5Ueq(Cmethyl)], using a riding model with C—H(aromatic) = 0.95 Å, C—H(methyl) = 0.98 Å and C—H(methylene) = 0.99 Å. The methyl group was allowed to rotate but not to tip. The hydroxy H atom was refined isotropically.
Data collection: X-AREA (Stoe & Cie, 2001); cell refinement: X-AREA; data reduction: X-AREA; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL-Plus (Sheldrick, 1991); software used to prepare material for publication: SHELXL97.
![]() | Fig. 1. Perspective view of (I), with the atom-numbering scheme; displacement ellipsoids are drawn at the 50% probability level. |
C14H15ClN2O2 | F(000) = 584 |
Mr = 278.73 | Dx = 1.306 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 5126 reflections |
a = 10.6426 (13) Å | θ = 3.5–25.1° |
b = 7.3564 (8) Å | µ = 0.27 mm−1 |
c = 18.467 (2) Å | T = 173 K |
β = 101.409 (9)° | Block, colourless |
V = 1417.2 (3) Å3 | 0.29 × 0.15 × 0.14 mm |
Z = 4 |
Stoe IPDS-II two-circle diffractometer | 2526 independent reflections |
Radiation source: fine-focus sealed tube | 1680 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.063 |
ω scans | θmax = 25.2°, θmin = 3.6° |
Absorption correction: empirical (using intensity measurements) (MULABS; Spek, 1990; Blessing, 1995) | h = −12→12 |
Tmin = 0.936, Tmax = 0.970 | k = −8→8 |
9173 measured reflections | l = −20→22 |
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)] = 0.036 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.078 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.88 | w = 1/[σ2(Fo2) + (0.0382P)2] where P = (Fo2 + 2Fc2)/3 |
2526 reflections | (Δ/σ)max < 0.001 |
177 parameters | Δρmax = 0.17 e Å−3 |
0 restraints | Δρmin = −0.25 e Å−3 |
C14H15ClN2O2 | V = 1417.2 (3) Å3 |
Mr = 278.73 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 10.6426 (13) Å | µ = 0.27 mm−1 |
b = 7.3564 (8) Å | T = 173 K |
c = 18.467 (2) Å | 0.29 × 0.15 × 0.14 mm |
β = 101.409 (9)° |
Stoe IPDS-II two-circle diffractometer | 2526 independent reflections |
Absorption correction: empirical (using intensity measurements) (MULABS; Spek, 1990; Blessing, 1995) | 1680 reflections with I > 2σ(I) |
Tmin = 0.936, Tmax = 0.970 | Rint = 0.063 |
9173 measured reflections |
R[F2 > 2σ(F2)] = 0.036 | 0 restraints |
wR(F2) = 0.078 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.88 | Δρmax = 0.17 e Å−3 |
2526 reflections | Δρmin = −0.25 e Å−3 |
177 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 | ||
C1 | 0.38571 (18) | 0.4615 (2) | 0.65428 (9) | 0.0235 (4) | |
C2 | 0.33171 (19) | 0.5641 (2) | 0.59548 (9) | 0.0274 (4) | |
H2 | 0.2410 | 0.5682 | 0.5812 | 0.033* | |
C3 | 0.4085 (2) | 0.6675 (2) | 0.55394 (10) | 0.0294 (4) | |
O3 | 0.36219 (15) | 0.7598 (2) | 0.49852 (8) | 0.0443 (4) | |
N4 | 0.53815 (17) | 0.6559 (2) | 0.57966 (8) | 0.0285 (4) | |
N5 | 0.59594 (16) | 0.5555 (2) | 0.63933 (8) | 0.0276 (4) | |
C6 | 0.52376 (19) | 0.4621 (2) | 0.67516 (9) | 0.0244 (4) | |
C61 | 0.5932 (2) | 0.3547 (3) | 0.74023 (11) | 0.0317 (4) | |
H61A | 0.5805 | 0.2245 | 0.7301 | 0.048* | |
H61B | 0.5594 | 0.3866 | 0.7842 | 0.048* | |
H61C | 0.6849 | 0.3830 | 0.7488 | 0.048* | |
C7 | 0.31126 (19) | 0.3526 (3) | 0.70088 (10) | 0.0286 (4) | |
H7A | 0.3384 | 0.2240 | 0.7006 | 0.034* | |
H7B | 0.3344 | 0.3966 | 0.7525 | 0.034* | |
C8 | 0.6310 (2) | 0.7559 (3) | 0.54534 (11) | 0.0347 (5) | |
H8A | 0.5845 | 0.8231 | 0.5017 | 0.042* | |
H8B | 0.6894 | 0.6684 | 0.5281 | 0.042* | |
C9 | 0.7088 (2) | 0.8882 (3) | 0.59861 (10) | 0.0342 (5) | |
H9A | 0.7551 | 0.8208 | 0.6422 | 0.041* | |
H9B | 0.7734 | 0.9470 | 0.5745 | 0.041* | |
O9 | 0.63120 (18) | 1.02425 (19) | 0.62231 (8) | 0.0433 (4) | |
H9 | 0.612 (3) | 1.100 (4) | 0.5903 (17) | 0.078 (10)* | |
C11 | 0.16773 (19) | 0.3608 (2) | 0.67672 (10) | 0.0283 (4) | |
C12 | 0.1004 (2) | 0.2468 (3) | 0.62183 (11) | 0.0327 (5) | |
Cl12 | 0.18342 (6) | 0.08265 (8) | 0.58149 (3) | 0.04721 (17) | |
C13 | −0.0316 (2) | 0.2588 (3) | 0.59889 (13) | 0.0444 (6) | |
H13 | −0.0749 | 0.1816 | 0.5608 | 0.053* | |
C14 | −0.0994 (2) | 0.3828 (4) | 0.63147 (14) | 0.0554 (7) | |
H14 | −0.1898 | 0.3909 | 0.6161 | 0.066* | |
C15 | −0.0361 (3) | 0.4955 (3) | 0.68653 (15) | 0.0535 (6) | |
H15 | −0.0832 | 0.5802 | 0.7095 | 0.064* | |
C16 | 0.0957 (2) | 0.4855 (3) | 0.70835 (12) | 0.0403 (5) | |
H16 | 0.1382 | 0.5653 | 0.7457 | 0.048* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0308 (11) | 0.0200 (8) | 0.0199 (8) | −0.0025 (7) | 0.0054 (8) | −0.0035 (7) |
C2 | 0.0313 (11) | 0.0268 (9) | 0.0229 (9) | −0.0054 (8) | 0.0029 (8) | −0.0001 (8) |
C3 | 0.0407 (13) | 0.0252 (9) | 0.0215 (9) | −0.0076 (9) | 0.0043 (9) | −0.0005 (8) |
O3 | 0.0527 (11) | 0.0481 (9) | 0.0289 (8) | −0.0121 (8) | −0.0001 (7) | 0.0168 (7) |
N4 | 0.0381 (10) | 0.0268 (8) | 0.0230 (8) | −0.0066 (7) | 0.0121 (7) | 0.0010 (6) |
N5 | 0.0315 (9) | 0.0259 (8) | 0.0271 (8) | 0.0006 (7) | 0.0098 (7) | −0.0006 (7) |
C6 | 0.0343 (11) | 0.0186 (8) | 0.0218 (9) | −0.0007 (8) | 0.0094 (8) | −0.0021 (7) |
C61 | 0.0319 (12) | 0.0281 (9) | 0.0343 (10) | 0.0015 (8) | 0.0043 (9) | 0.0061 (8) |
C7 | 0.0308 (11) | 0.0298 (9) | 0.0250 (9) | −0.0073 (8) | 0.0044 (8) | 0.0035 (7) |
C8 | 0.0457 (13) | 0.0357 (10) | 0.0271 (10) | −0.0126 (10) | 0.0181 (10) | −0.0022 (8) |
C9 | 0.0444 (13) | 0.0329 (10) | 0.0282 (10) | −0.0102 (10) | 0.0143 (9) | −0.0002 (8) |
O9 | 0.0750 (12) | 0.0285 (7) | 0.0291 (8) | −0.0010 (8) | 0.0171 (8) | 0.0037 (6) |
C11 | 0.0331 (12) | 0.0285 (9) | 0.0242 (9) | −0.0057 (8) | 0.0081 (8) | 0.0053 (7) |
C12 | 0.0350 (12) | 0.0358 (10) | 0.0294 (10) | −0.0103 (9) | 0.0113 (9) | −0.0002 (8) |
Cl12 | 0.0564 (4) | 0.0474 (3) | 0.0415 (3) | −0.0104 (3) | 0.0186 (3) | −0.0148 (3) |
C13 | 0.0350 (14) | 0.0584 (14) | 0.0389 (12) | −0.0169 (11) | 0.0050 (11) | 0.0029 (10) |
C14 | 0.0319 (13) | 0.0766 (18) | 0.0578 (15) | 0.0006 (13) | 0.0091 (12) | 0.0144 (14) |
C15 | 0.0489 (16) | 0.0545 (14) | 0.0613 (16) | 0.0143 (12) | 0.0211 (13) | 0.0055 (12) |
C16 | 0.0458 (14) | 0.0377 (11) | 0.0387 (11) | −0.0015 (10) | 0.0112 (10) | −0.0027 (9) |
C1—C2 | 1.354 (3) | C8—H8A | 0.9900 |
C1—C6 | 1.443 (3) | C8—H8B | 0.9900 |
C1—C7 | 1.510 (2) | C9—O9 | 1.421 (3) |
C2—C3 | 1.443 (3) | C9—H9A | 0.9900 |
C2—H2 | 0.9500 | C9—H9B | 0.9900 |
C3—O3 | 1.246 (2) | O9—H9 | 0.81 (3) |
C3—N4 | 1.370 (3) | C11—C16 | 1.395 (3) |
N4—N5 | 1.367 (2) | C11—C12 | 1.399 (3) |
N4—C8 | 1.472 (2) | C12—C13 | 1.387 (3) |
N5—C6 | 1.304 (2) | C12—Cl12 | 1.748 (2) |
C6—C61 | 1.504 (3) | C13—C14 | 1.374 (3) |
C61—H61A | 0.9800 | C13—H13 | 0.9500 |
C61—H61B | 0.9800 | C14—C15 | 1.380 (4) |
C61—H61C | 0.9800 | C14—H14 | 0.9500 |
C7—C11 | 1.506 (3) | C15—C16 | 1.383 (4) |
C7—H7A | 0.9900 | C15—H15 | 0.9500 |
C7—H7B | 0.9900 | C16—H16 | 0.9500 |
C8—C9 | 1.509 (3) | ||
C2—C1—C6 | 117.45 (17) | C9—C8—H8A | 109.3 |
C2—C1—C7 | 124.44 (18) | N4—C8—H8B | 109.3 |
C6—C1—C7 | 118.07 (15) | C9—C8—H8B | 109.3 |
C1—C2—C3 | 121.66 (19) | H8A—C8—H8B | 107.9 |
C1—C2—H2 | 119.2 | O9—C9—C8 | 112.17 (18) |
C3—C2—H2 | 119.2 | O9—C9—H9A | 109.2 |
O3—C3—N4 | 121.78 (18) | C8—C9—H9A | 109.2 |
O3—C3—C2 | 123.4 (2) | O9—C9—H9B | 109.2 |
N4—C3—C2 | 114.86 (16) | C8—C9—H9B | 109.2 |
N5—N4—C3 | 125.06 (15) | H9A—C9—H9B | 107.9 |
N5—N4—C8 | 112.57 (16) | C9—O9—H9 | 110 (2) |
C3—N4—C8 | 122.36 (16) | C16—C11—C12 | 116.9 (2) |
C6—N5—N4 | 118.51 (16) | C16—C11—C7 | 120.73 (18) |
N5—C6—C1 | 122.44 (16) | C12—C11—C7 | 122.37 (18) |
N5—C6—C61 | 115.88 (17) | C13—C12—C11 | 121.7 (2) |
C1—C6—C61 | 121.68 (16) | C13—C12—Cl12 | 118.73 (17) |
C6—C61—H61A | 109.5 | C11—C12—Cl12 | 119.54 (16) |
C6—C61—H61B | 109.5 | C14—C13—C12 | 119.8 (2) |
H61A—C61—H61B | 109.5 | C14—C13—H13 | 120.1 |
C6—C61—H61C | 109.5 | C12—C13—H13 | 120.1 |
H61A—C61—H61C | 109.5 | C13—C14—C15 | 120.0 (2) |
H61B—C61—H61C | 109.5 | C13—C14—H14 | 120.0 |
C11—C7—C1 | 115.23 (15) | C15—C14—H14 | 120.0 |
C11—C7—H7A | 108.5 | C14—C15—C16 | 120.1 (2) |
C1—C7—H7A | 108.5 | C14—C15—H15 | 119.9 |
C11—C7—H7B | 108.5 | C16—C15—H15 | 119.9 |
C1—C7—H7B | 108.5 | C15—C16—C11 | 121.5 (2) |
H7A—C7—H7B | 107.5 | C15—C16—H16 | 119.3 |
N4—C8—C9 | 111.71 (15) | C11—C16—H16 | 119.3 |
N4—C8—H8A | 109.3 | ||
C6—C1—C2—C3 | 1.3 (3) | C6—C1—C7—C11 | 178.97 (15) |
C7—C1—C2—C3 | 178.96 (16) | N5—N4—C8—C9 | −60.6 (2) |
C1—C2—C3—O3 | 178.21 (18) | C3—N4—C8—C9 | 118.4 (2) |
C1—C2—C3—N4 | −1.3 (3) | N4—C8—C9—O9 | −62.3 (2) |
O3—C3—N4—N5 | −179.01 (17) | C1—C7—C11—C16 | −94.8 (2) |
C2—C3—N4—N5 | 0.5 (3) | C1—C7—C11—C12 | 84.6 (2) |
O3—C3—N4—C8 | 2.1 (3) | C16—C11—C12—C13 | 1.1 (3) |
C2—C3—N4—C8 | −178.41 (16) | C7—C11—C12—C13 | −178.41 (18) |
C3—N4—N5—C6 | 0.2 (2) | C16—C11—C12—Cl12 | −178.18 (14) |
C8—N4—N5—C6 | 179.24 (15) | C7—C11—C12—Cl12 | 2.4 (2) |
N4—N5—C6—C1 | −0.2 (2) | C11—C12—C13—C14 | −1.3 (3) |
N4—N5—C6—C61 | −179.98 (15) | Cl12—C12—C13—C14 | 177.91 (17) |
C2—C1—C6—N5 | −0.5 (2) | C12—C13—C14—C15 | 0.4 (4) |
C7—C1—C6—N5 | −178.33 (15) | C13—C14—C15—C16 | 0.8 (4) |
C2—C1—C6—C61 | 179.20 (16) | C14—C15—C16—C11 | −1.1 (4) |
C7—C1—C6—C61 | 1.4 (2) | C12—C11—C16—C15 | 0.2 (3) |
C2—C1—C7—C11 | 1.4 (3) | C7—C11—C16—C15 | 179.63 (19) |
D—H···A | D—H | H···A | D···A | D—H···A |
O9—H9···O3i | 0.81 (3) | 2.00 (3) | 2.751 (2) | 154 (3) |
Symmetry code: (i) −x+1, −y+2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C14H15ClN2O2 |
Mr | 278.73 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 173 |
a, b, c (Å) | 10.6426 (13), 7.3564 (8), 18.467 (2) |
β (°) | 101.409 (9) |
V (Å3) | 1417.2 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.27 |
Crystal size (mm) | 0.29 × 0.15 × 0.14 |
Data collection | |
Diffractometer | Stoe IPDS-II two-circle diffractometer |
Absorption correction | Empirical (using intensity measurements) (MULABS; Spek, 1990; Blessing, 1995) |
Tmin, Tmax | 0.936, 0.970 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9173, 2526, 1680 |
Rint | 0.063 |
(sin θ/λ)max (Å−1) | 0.600 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.036, 0.078, 0.88 |
No. of reflections | 2526 |
No. of parameters | 177 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.17, −0.25 |
Computer programs: X-AREA (Stoe & Cie, 2001), X-AREA, SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), XP in SHELXTL-Plus (Sheldrick, 1991), SHELXL97.
C3—N4 | 1.370 (3) | N5—C6 | 1.304 (2) |
N4—N5 | 1.367 (2) | C9—O9 | 1.421 (3) |
N4—C8 | 1.472 (2) | C12—Cl12 | 1.748 (2) |
N5—N4—C3 | 125.06 (15) | C3—N4—C8 | 122.36 (16) |
N5—N4—C8 | 112.57 (16) | C6—N5—N4 | 118.51 (16) |
D—H···A | D—H | H···A | D···A | D—H···A |
O9—H9···O3i | 0.81 (3) | 2.00 (3) | 2.751 (2) | 154 (3) |
Symmetry code: (i) −x+1, −y+2, −z+1. |
Many pyridazine compounds have been reported to be anticonvulsive agents (Rubat et al., 1990; Foussard-Blanc & Lacroix, 1991). Furthermore, Gehrlein et al. (1981) have described the antihypertensive effects of novel hydroxyethylpyridazine compounds. In continuation of this line of investigation, we have synthesized compound (I); it will be subjected to further pharmacological investigations, especially tests of its anticancer activity. Compound (I) is stable at room temperature, and its structure has been determined by IR, MS and NMR (1H and 13C) spectroscopy. Since these techniques did not provide sufficient information about the conformation of the reaction product, we have carried out an X-ray structure analysis. The bond lengths and angles of (I) are normal (Table 1). The dihedral angle between the two rings is 85.71 (5)°. In the crystal structure, molecules of (I) form hydrogen-bonded centrosymmetric dimers (Table 2).
The structure of a very similar compound, (II), in which the N atom carries a H atom instead of a 2-hydroxyethyl group, has been determined by Moreau et al. (1995). However, the conformations of the two compounds are completely different, as can be seen by the torsion angle C12—C11—C7—C1, which is 84.6 (2)° in the title compound and 149.6° in (II). The reason for this difference may be due to the different packing patterns. Whereas the title compound crystallizes as centrosymmetric hydrogen-bonded dimers, compound (II) contains hydrogen-bonded zigzag chains.