Reaction of Tertiary 2-Chloroketones with Cyanide Ions: Application to 3-Chloroquinolinediones.

3-Chloroquinoline-2,4-diones react with cyanide ions in dimethyl formamide to give 3-cyanoquinoline-2,4-diones in small yields due to the strong hindrance of the substituent at the C-3 atom. Good yields can be achieved if the substituent at this position is the methyl group. In the methanol solution, the reaction proceeds by an addition mechanism to form 2-oxo-1a,2,3,7b-tetrahydrooxireno[2,3-c]quinoline-7b-carbonitriles, from which 4-hydroxy-3-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline-4-carbonitriles are subsequently formed by opening of the epoxide ring with methanol.

Preparation of Quinoline-2,4-dione Functionalized 1,2,3-Triazol-4-ylmethanols, 1,2,3-Triazole-4-carbaldehydes and 1,2,3-Triazole-4-carboxylic Acids.

(1-(2,4-Dioxo-1,2,3,4-tetrahydroquinolin-3-yl)-1H-1,2,3-triazol-4-yl)methyl acetates substituted on nitrogen atom of quinolinedione moiety with propargyl group or (1-substituted 1H-1,2,3-triazol-4-yl)methyl group, which are available from the appropriate 3-(4-hydroxymethyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-diones unsubstituted on quinolone nitrogen atom by the previously described procedures, were deacetylated by acidic ethanolysis. Thus obtained primary alcohols, as well as those aforenamed unsubstituted on quinolone nitrogen atom, were oxidized to aldehydes on the one hand with pyridinium chlorochromate (PCC), on the other hand with manganese dioxide, and to carboxylic acids using Jones reagent in acetone. The structures of all prepared compounds were confirmed by 1H, 13C and 15N NMR spectroscopy.

Synthesis of Bis(1,2,3-Triazole) Functionalized Quinoline-2,4-Diones.

Derivatives of 3-(1-1,2,3-triazol-1-yl)quinoline-2,4(1,3)-dione unsubstituted on quinolone nitrogen atom, which are available by the previously described four step synthesis starting from aniline, were exploited as intermediates in obtaining the title compounds. The procedure involves the introduction of propargyl group onto the quinolone nitrogen atom of mentioned intermediates by the reaction of them with propargyl bromide in ,-dimethylformamide (DMF) in presence of a potassium carbonate and the subsequent formation of a second triazole ring by copper catalyzed cyclisation reaction with azido compounds. The products were characterized by ¹H, C and N NMR spectroscopy.

Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones.

In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 μM and against Mycobacterium bovis AN5A below 15 μM but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox™ assay at the active concentration range.

Synthesis of 1,4-Benzodiazepine-2,5-diones by Base Promoted Ring Expansion of 3-Aminoquinoline-2,4-diones.

An unprecedented reactivity of 3-aminoquinoline-2,4-diones is reported. Under basic conditions, these compounds undergo molecular rearrangement to furnish 1,4-benzodiazepine-2,5-diones. The transformations take place under mild reaction conditions by using 1,1,3,3-tetramethylguanidine, NaOEt, or benzyltrimethylammonium hydroxide as a base.

Fischer indolisation of N-(α-ketoacyl)anthranilic acids into 2-(indol-2-carboxamido)benzoic acids and 2-indolyl-3,1-benzoxazin-4-ones and their NMR study.

N-(α-ketoacyl)anthranilic acids reacted with phenylhydrazinium chloride in boiling acetic acid to afford 2-(indol-2-carboxamido)benzoic acids in good to excellent yields and 2-indolyl-3,1-benzoxazin-4-ones as by-products. The formation of the latter products could easily be suppressed by a hydrolytic workup. Alternatively, by increasing the reaction temperature and/or time, 2-indolyl-3,1-benzoxazin-4-ones can be obtained exclusively.

4-Hy-droxy-1-methyl-3-phenyl-quinolin-2(1H)-one.

In the title compound, C(16)H(13)NO(2), the quinoline system is approximately planar with a maximum deviation from the least-squares plane of 0.059 (1) Å for the N atom. The phenyl ring is rotated by 62.

3-Ethyl-3-hy-droxy-8-meth-oxy-quinoline-2,4(1H,3H)-dione monohydrate.

In the title hydrate, C(12)H(13)NO(4)·H(2)O, the piperidine ring that is fused to the benzene ring is in a sofa conformation with the chiral C atom lying 0.4084 (18) Å out of the plane of the nine fused-ring atoms. In the crystal, O-H⋯O and N-H⋯O hydrogen bonds link the organic mol-ecules and water mol-ecules into chains running along the b-axis direction.

3-Ethyl-4-hy-droxy-8-meth-oxy-quinolin-2(1H)-one.

In the title compound, C(12)H(13)NO(3), the quinoline ring system is approximately planar with a maximum deviation from the least-squares plane of 0.058 (2) Å. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds link the mol-ecules into chains running along the b-axis direction.

2-Hy-droxy-2-methyl-1-phenyl-indolin-3-one.

In the title compound, C(15)H(13)NO(2), the indole and benzene rings make a dihedral angle of 60.61 (4)°. In the crystal, dimeric pairs (twofold symmetry) are formed via O-H⋯O hydrogen bonds.

Selective formation of glycosidic linkages of N-unsubstituted 4-hydroxyquinolin-2-(1H)-ones.

A comparative study for selective glucosylation of N-unsubstituted 4-hydroxyquinolin-2(1H)-ones into 4-(tetra-O-acetyl-beta-D-glucopyranosyloxy)quinolin-2(1H)-ones is reported. Four glycosyl donors including tetra-O-acetyl-alpha-D-glucopyranosyl bromide, beta-D-glucose pentaacetate, glucose tetraacetate and tetra-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate were tested, along with different promoters and reaction conditions. The best results were obtained with tetra-O-acetyl-alpha-D-glucopyranosyl bromide with Cs(2)CO(3) in CH(3)CN.

3-Ethyl-8-meth-oxy-4-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranos-yloxy)quinolin-2(1H)-one.

The structure of the title compound, C(26)H(31)NO(12), contains an essentially planar quinoline skeleton, with the maximum deviation from the best plane being 0.055 (2) Å, and an oxane ring in a classical chair conformation with the following Cremer and Pople puckering parameters: Q = 0.586 (2) Å, θ = 11.

Formation and structure elucidation of two novel spiro[2H-indol]-3(1H)-ones.

The molecular structures of two byproducts 1,1''-diphenyl-3',4'-dihydrodispiro[indole-2,2'-furan-5',2''-indole]-3,3''(1H, 1''H)-dione (3) and 1,5'-diphenyl-4',5'-dihydro-3'H-spiro[indole-2,2'-pyrano[3,2-b]indol]-3(1H)-one (4), which accompanied the rearrangement of 3-hydroxy-3-methyl-1-phenylquinoline-2,4(1H,3H)-dione (1) to 2-hydroxy-2-methyl-1-phenyl-1,2-dihydro-3H-indol-3-one (2), have been elucidated by NMR, MS, and X-ray diffraction.

New modification of the Perkow reaction: halocarboxylate anions as leaving groups in 3-acyloxyquinoline-2,4(1H,3H)-dione compounds.

Substituted 3-(fluoroacyloxy)quinoline-2,4(1H,3H)-diones including 3-(fluoroiodoacetoxy) derivatives react with triethyl phosphite to afford either the product of the Perkow reaction or the corresponding 4-ethoxyquinolin-2(1H)-one. In both reactions, the fluorocarboxylate anion acts as the first observed leaving group. This observation restricts the application of the intramolecular Horner-Wadsworth-Emmons synthesis to modify quinoline-2,4(1H,3H)-diones by the annulation of fluorinated but-2-enolide rings.