Antonín Klásek

Syntheses of 3-Aminoquinoline- 2,4(1H,3H)-diones

Reaction of 3-chloro- (2) and 3-bromoquinoline-2,4(1H,3H)-diones (3) with excess of primary alkyl- or arylamines in dimethylformamide provides the corresponding 3-alkyl- or 3-arylamino derivatives (4). Compounds (4) with the primary amino group at the 3 position were best prepared by reaction of 2 with in situ generated ammonia under anhydrous conditions. An alternative approach to the primary amines (4) via reduction of 3-azidoquinoline-2,4(1H,3H)-diones (5) was investigated. The reduction of 5 with zinc in acetic acid gave moderate to good yields of the desired products, while the reaction with triphenylphosphine afforded exclusively 4-hydroxyquinolin-2(1H)-one (1).

Synthesis of novel 3-acyloxy-1,3-dihydro-2H-indol-2-ones and isomeric 4- acyl-1,4-dihydro-3,1-benzoxazin-2-ones: Double rearrangement of 3- hydroxyquinoline-2,4(1H,3H)-diones

Abstract Substituted 3-hydroxyquinoline-2,4(1 H ,3 H )-diones 3 were transformed into 3-acyloxy-1,3-dihydro-2 H -indol-2-ones 4 and isomeric 4-acyl-1,4-dihydro-3,1-benzoxazin-2-ones 5 . The influence of the substituents and the reaction conditions on the course of the reaction was studied. In the proposed mechanism a double rearrangement takes place; α-ketol rearrangement of 3 , leading to α-hydroxy-β-diketone intermediate 8 , is followed by a rearrangement to the isomeric α-ketol-esters 4 and 5 .

Unprecedented reactivity of 3-amino-1H,3H-quinoline-2,4-diones with urea: an efficient synthesis of 2,6-dihydro-imidazo(1,5-c)quinazoline-3,5-diones

Abstract Substituted 3-amino-1H,3H-quinoline-2,4-diones react with urea in acetic acid to give novel 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones in high yields. The same compounds were obtained, albeit with small yields, from 3-chloro-1H,3H-quinoline-2,4-diones and urea. In the proposed reaction mechanism, a molecular rearrangement of the primarily formed mono-substituted urea takes place. The prepared 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones were characterized by their 1H, 13C, 15N NMR and IR spectra and atmospheric pressure chemical ionisation mass spectra.

Reaction of 1-alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones with urea. Synthetic route to novel 3-(3-acylureido)-2,3-dihydro-1H-indol-2-ones, 4-alkylidene-1′H-spiro[imidazolidine-5,3′-indole]-2,2′-diones, and 3,3a-dihydro-5H-imidazo[4,5-c]quinoline-2,4-diones

Abstract 1-Substituted 3-alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with urea in boiling acetic acid to give products depending on the type of substitution in position 3 and at the nitrogen atom of the 3-amino group. Starting compounds bearing a primary amino group in position 3 give 3-(3-acylureido)-2,3-dihydro-1H-indol-2-ones. Starting compounds bearing a secondary amino group in position 3 react according to the character of the other substituent in position 3. If there is a hydrogen atom α to the carbon atom C(3), 4-alkylidene-1′H-spiro[imidazolidine-5,3′-indole]-2,2′-diones arise. If a hydrogen atom is not present in this position, the reaction leads to 3,3a-dihydro-5H-imidazo[4,5-c]quinoline-2,4-diones. Reaction mechanisms for these transformations are proposed. All compounds were characterized by their 1H, 13C, IR and atmospheric pressure chemical ionization mass spectra and some of them also by 15N NMR data.

Preparation of 1‐monoacyIgIyceroIs from gIycidoI and fatty acids cataIyzed by the chromium(III)‐fatty acid system

A description is given for preparing 1-monoacylglycerols by the reaction of fatty acids with glycidol catalyzed by Cr(III)-fatty acid complexes. These complexes were found to possess catalytic efficiency substantially greater than catalysts employed earlier. Effects of catalyst type, its content in the mixture, molar ratio of reactants, and reaction temperature during the course of acid conversion were studied. With a catalyst content of 0.5% by mass of charged reactants and at 90 °C a 90— 95% conversion of the acid can be achieved within 60 min. In addition to the corresponding 1-monoacylglycerol, only unreacted starting substances and the catalyst were detected in resulting reaction mixtures.

Thermal rearrangement of 3-hydroxy-1H, 3H-quinoline-2,4-diones to 3-acyloxy-2,3-dihydro-1H-indol-2-ones

3-Alkyl/aryl-3-hydroxy-1H,3H-quinoline-2,4-diones (2) were transformed into isomeric 3-acyloxy-2,3-dihydro-1H-indol-2-ones (3) by thermally induced molecular rearrangement. All products were characterized by their 1 H NMR, 1 3 C NMR, and IR spectra.

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.

A new synthesis of 4-alkyl/aryl-5,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5-diones and molecular rearrangement of their 3-bromo derivatives to 2-alkyl/aryl-4-oxo-4,5-dihydrofuro[3,2-c]quinoline-3-carboxylic acids

The treatment of 3-acyl-4-hydroxy-1H-quinolin-2-ones (1) with ethyl (triphenylphosphoranylidene)acetate leads to 5,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5-diones (2), which were brominated to 3-bromo derivatives (4). Alkaline hydrolysis of 4 gives 2-alkyl/aryl-4-oxo-4,5-dihydrofuro[3,2-c]quinoline-3-carboxylic acids (6), which were decarboxylated to 2-alkyl/aryl-5H-furo[3,2-c]quinolin-4-ones (8). The reaction of 3-acetyl-4-hydroxy-1-methyl-1H-quinolin-2-one (la) with ethyl (triphenylphosphoranylidene)chloroacetate proceeds not only at the acetyl but also at the amide group to give a mixture of ethyl 3,5-dimethyl-4-oxo-4,5-dihydrofuro[3,2-c]quinoline-2-carboxylate (11a) and ethyl 4,6-dimethyl-2-oxo-5,6-dihydro-2H-pyrano[3,2-c]quinolin-5-ylidene-(chloro)acetate (12a). The reaction mechanism of the molecular rearrangement of 4 to 6 is discussed.

Esters with imidazo [1,5-c] quinazoline-3,5-dione ring spectral characterization and quantum-mechanical modeling

Abstract1-phenyl-2H,6H-imidazo[1,5-c]quinazoline-3,5-dione reacts with ethyl bromoacetate under mild conditions to give 2-(ethoxycarbonylmethyl)-1-phenyl-6H-imidazo[1,5-c]quinazoline-3,5-dione (MEPIQ) and next 2,6-bis(ethoxycarbonylmethyl)-1-phenylimidazo[1,5-c]quinazoline-3,5-dione (BEPIQ). The products were isolated at high yield and identified on the basis of IR, 1H- and 13C-NMR, UV spectroscopy, and X-ray crystallography. Diester (BEPIQ) can be presented by 16 possible pair of enantiomers. Only one pair of them is the most stable and crystallizes which is shown crystallographic research. Based on quantum-mechanical modeling, with the use of DFT method, which conformers of mono- and diester and why they were formed was explained. It was calculated that 99.93% of the monoester (MEPIQ) is formed at position No. 2 and one pair of the monoester conformers, from six possible, has the largest share (51.63%). These results afforded to limit the number of diester conformers to eight. Unfortunately, the quantum-mechanical calculations performed that their shares are similar. Further quantum-mechanical modeling showed that conformers are able to undergo mutual transformations. As a result only one pair of diester conformers forms crystals. These conformers have substituents in trans position and these substituents are located parallel to imidazoquinazoline ring. This allows for the denser packing of the molecules in the unit cell.

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. A proposed mechanism of the rearrangement and the conformational equilibrium of 1,4-benzodiazepine-2,5-dione rings are discussed.