EXPERIMENTAL
The 1H NMR spectra of the acetylquinoline 1 and hydrazone 5 were recorded on a Varian Mercury VX-200
spectrometer (200 MHz) using DMSO-d6 solvent and TMS internal standard. Mass spectra for the acylhydrazones
4a-h were obtained on a Varian 1200L instrument in full scanning mode in the range 45-550 m/z with 70 eV EI
ionization and direct introduction of the sample. The ethyl esters and hydrazides of the 1-R-4-hydroxy-2-oxo-
1,2 dihydroquinoline-3-carboxylic acids were prepared by the methods reported in [15] and [16] respectively.
3-Acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline (1). A mixture of freshly distilled acetoacetic ester
(13.9 ml, 0.11 mol), xylene (20 ml, commercial mixture of isomers), and triethanolamine (1 g) was heated to
reflux. A solution of methyl anthranilate 2 (12.9 ml, 0.1 mol) in xylene (30 ml) was added dropwise to the
refluxing solution not allowing a marked fall in temperature. The ethanol formed in the reaction was removed
via a fractionating column. After addition of all of the methyl anthranilate the refluxing was continued for about
1 h while distilling from it a mixture of xylene and alcohol (20 ml). The solution of the 2-carbomethoxyanilde 3
in xylene obtained was cooled and a solution of NaOH (12.0 g, 0.3 mol) in water (100 ml) was added to it with
stirring. Cyclization occurred with a marked evolution of heat and required much external cooling ! Stirring was
continued for 1 h, the organic layer was separated, and the aqueous was purified using carbon and then acidified
using dilute (1:1) HCl to pH 4-5. The precipitated acetylquinoline 1 produced was filtered off, washed with cold
1
water, and dried. Yield 18.5 g (91%); mp 252-254ºC (DMF). H NMR spectrum, δ, ppm (J, Hz): 16.81 (1H, s,
OH); 11.52 (1H, s, NH); 7.96 (1H, d, J = 8.0, H-5); 7.66 (1H, td, J = 7.8 and J = 1.5, H-7); 7.27 (1H, d, J = 8.0,
H-8); 7.21 (1H, t, J =7.5, H-6); 2.70 (3H, s, CH3).
X-ray Crystallographic Investigation. Crystals of the acetylquinoline 1 are monoclinic (DMF), at 20ºC: a
= 9.309(2), b = 5.209(2), c = 18.505(6) Å, β = 91.53(2)º, V = 897.0(5) Å3, Mr = 203.19, Z = 4, space group P21/n,
d
calc = 1.505 g/cm3, µ(MoKα) = 0.111 mm-1, F(000) = 424. Unit cell parameters and intensities of 4955 reflections
(1564 independent, Rint = 0.023) were measured on an Xcalibur-3 diffractometer (MoKα radiation, CCD detector,
graphite monochromator, ω-scanning to 2θmax = 50º). The structure was solved by a direct method using the
SHELXTL package [17]. The positions of the hydrogen atoms were revealed from electron density difference
synthesis and refined using the "riding" model with Uiso = nUeq (n = 1.5 for a methyl group and n = 1.2 for other
hydrogen atoms). The positions of the hydrogen atoms taking part in hydrogen bonding were refined in the
isotropic approximation. The structure was refined by F2 full matrix least squares analysis in the anisotropic
approximation for non-hydrogen atoms to wR2 = 0.083 for 1541 reflections (R1 = 0.033 for 994 reflections with
F > 4σ(F), S = 0.860). The full crystallographic information has been placed in the Cambridge structural database
(reference No. CCDC 672206). Interatomic distances and valence angles are given in Tables 1 and 2.
3-(1-Hydrazonoethyl)-4-hydroxy-1H-quinolin-2-one (5). An 80% aqueous solution of hydrazine
hydrate (2 ml) was added to a solution of the acetylquinoline 1 (2.03 g, 0.01 mol) in ethanol (50 ml) and
refluxed for 2 h. The product was cooled and the precipitated hydrazone 5 was filtered, washed with cold water,
1
and dried. Yield 1.87 g (86%); mp 291-293ºC (DMF). H NMR spectrum, δ, ppm (J, Hz): 16.12 (1H, s, OH);
10.60 (1H, s, NH); 7.90 (1H, dd, J = 8.1 and J = 1.5, H-5), 7.41 (1H, td, J = 7.7 and J = 1.6, H-7); 7.11 (1H, d,
J = 8.2, H-8); 7.03 (1H, td, J = 7.5 and J = 1.0, H-6); 6.00 (1H, s, NH2); 2.66 (3H, s, CH3). Found, %: C 60.71;
H 5.02; N 19.45. C11H11N3O2. Calculated, %: C 60.82; H 5.10; N 19.34.
4-Hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylc Acid [1-(4-Hydroxy-2-oxo-1,2-dihydro-
quinolin-3-yl)ethylidene]hydrazide (4a). A. 4-Hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid
hydrazide (2.33 g, 0.01 mol) was added to a solution of the acetylquinoline 1 (2.03 g, 0.01 mol) in DMF (30 ml) and
refluxed for 30 min. The acylhydrazone 4a was formed as a bulky light-yellow precipitate. It was filtered, washed
several times with alcohol, and dried.
B. Ethyl 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate (2.47 g, 0.01 mol) was added
to a solution of the hydrazone 5 (2.17 g, 0.01 mol) in DMF (30 ml) and refluxed for 1 h. The target compound
was separated by the method described above.
174