4-Hydroxy-2-quinolones. 26. Bromination of 3-substituted 2-oxo-4-hydroxyquinolones

Сидоренко

Golovchenko

2007

Chem Heterocycl Comp

Self Cite

The spatial structural features of 3-bromo-3-ethoxycarbonyl-2,4-dioxo-1,2,3,4-tetrahydroquinolines have been studied by X-ray analysis. It has been experimentally confirmed that these compounds can be regarded as potential brominating agents.The bromination route of ethyl 1R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids using molecular bromine in acetic acid depends on the presence of water in the reaction mixture. Its presence predetermines the formation of 1-R-3-bromo-3-ethoxycarbonyl-2,4-dioxo-1,2,3,4-tetrahydroquinolines. This reaction occurs instantly upon addition of bromine. On the other hand, after thorough dehydration of the reagents and solvent an electrophilic attack occurs only at position 6 of the quinolone ring and in this case completion of the bromination requires several hours [2]. In practice, carrying out the reaction with a strictly stoichiometric ratio of the reacting material and in absolutely anhydrous conditions could not always be achieved. As a consequence there was sometimes observed a partial formation of the 3-bromo-substituted isomers which, in contrast to the colorless 6-bromoquinolines, are bright yellow in color. This process does not, however, cause a significant problem since the high solubility in most organic solvents allows a ready removal of the unwanted admixture from the target 6-bromo derivatives.This formation of the 6-bromoquinolines has been confirmed by us via a counter synthesis using intermediate products with a well known position for the bromine atom in the molecule [3], e.g. from X-ray analysis. At the same time, the steric structural features of their 3-bromo-substituted isomers has remained obscure for a long time.In one of the bromination experiments [2] of ethyl 4-hydroxy-2-oxo-1-propyl-1,2-dihydroquinoline-3-carboxylate (1), prolonged cooling of the filtrate remaining after separation of the basic 6-bromoquinoline 2 at -25ºC caused the growth of several yellow single crystals which were subjected to X-ray analysis.

“…Water was removed from commercial carbon tetrachloride using P 2 O 5 . Ethyl 3-bromo-2,4-dioxo-1,2,3,4-tetrahydroquinoline-3-carboxylate (4) was prepared by the method given in [9].…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

4-hydroxy-2-quinolones 125. Ethyl 3-bromo-2,4-dioxo-1,2,3,4-tetrahydroquinoline-3-carboxylates as potential brominating agents

Сидоренко

Golovchenko

2007

Chem Heterocycl Comp

Self Cite

“…The colorless crystals produced were separated and repeatedly crystallized from aqueous acetone to give the furoquinolone hydrobromide 5 (1.94 g, 53%) (precipitation of salt 5 from the mixture using anhydrous ether gave a yield of 96%); mp 228-230ºC. 1 13 C NMR spectrum, δ, ppm: 165.3 (C (9a ), 164.6 (C=O), 139.2 (C (8a) ), 132.6 (C (7) ), 125.4 (C (6) ), 124.0 (C (5) ), 120.7 (C (80 ), 120.5 (C (4a) ), 102.4 (C (3a) ), 85.1 (CHO), 36.7 (CH 2 Br), 31.3 (C (3 B. A mixture of conc.…”

Section: -Allyl-4-hydroxy-2-oxo-12-dihydroquinoline (1) Was Preparementioning

confidence: 99%

“…Hence the reaction is not necessarily accompanied by heterocyclization and can present itself as a normal addition of bromine to the unsaturated allyl bond giving the 2,3-dibromopropyl derivative 2. We also do not exclude a bromination of the quinolone ring at position 3 [6] characteristic of 3-alkyl-4-hydroxy-2-oxo-1,2-dihydroquinolines to give the 3-allyl-3-bromo-2,4-dioxo-1,2,3,4-tetrahydroquinoline (3). However, if cyclization none the less occurs it leads to a furo-rather than oxazoloquinolone.…”

mentioning

confidence: 94%

4-Hydroxy-2-quinolones 131. Bromination of 3-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline

Bereznyakova

Gorokhova

et al. 2007

Chem Heterocycl Comp

Self Cite

Keywords: furo[2,3-b]quinolines, bromination, heterocyclization, X-ray structural analysis.Addition of molecular bromine to the unsaturated bond of the allyl fragments in 1-allyl substituted 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids and their ethyl esters occurs almost instantly in the absence of any kind of catalyst and is accompanied by the closure of an oxazole ring [2]. 1-Allyl-4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid reacts similarly with bromine with the difference that the final reaction product is 2-bromomethyl-4-carboxy-5-methyl-1,2-dihydrooxazolo[3,2-a]quinolinium bromide [3] because the tautomeric 1,4-dihydro form cannot occur. Hydrogenation of the benzene part of the N-allylquinolone molecule in no way affects the path of this interesting reaction [4]. But in the case of the 1-allyl-4-hydroxy-2-oxo-1,2-dihydroquinolines and pyridines unsubstituted in position 3 only the 4-bromo-2-bromomethyl-1,2-dihydrooxazolo[3,2-a]quinolin-and pyridin-5-ones can be separated because the initially formed 4H-2-bromomethyloxazoles are again brominated by the bromine not taking part in the reaction much more readily than the starting N-allyl derivatives [5].On the basis of the experiments carried out by us previously we can conclude that a necessary condition for formation of the 2-bromomethyloxazole ring annelated to the azaheterocycle is the presence in the molecule undergoing bromination of an N-allyl-1,2-dihydropyridin-2-one fragment. This does not exclude other nitrogen containing heterocycles containing a carbonyl or, possibly a hydroxyl group in the ortho position to the cyclic allyl substituted nitrogen atom undergoing a similar reaction but for now such a proposal has not been confirmed experimentally.In this investigation we have studied the bromination of 3-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline (1).

“…It is known that 3-alkyl-, 3-phenyl-, and 3-alkoxycarbonyl-substituted 4-hydroxy-2-oxo-1,2-dihydroquinolines (including N-phenyl) are brominated by molecular bromine in glacial acetic acid at position 3 to give 3-bromo-3-R-2,4-dioxo-1,2,3,4-tetrahydroquinolines [13,14].…”

mentioning

confidence: 99%

4-hydroxy-2-quinolones. 110. Bromination of 1-r-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides

Ткач

Сидоренко

et al. 2006

Chem Heterocycl Compd

Self Cite

1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides have been prepared. It has been shown experimentally that these compounds are brominated by molecular bromine in glacial acetic acid at position 4 of the anilide fragment. The antitubercular properties of the compounds synthesized are discussed.Keywords: 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid amides, bromination, X-ray analysis, antitubercular activity.1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides possess a broad spectrum of biological activity. They include substances with antithyroid [2], antitubercular [3,4], analgesic, antiinflammatory [5], and antioxidant properties [6]. In medicine, the antineoplastic linomide (roquinimex, 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid N-methylanilide [7]) is used. Many investigation of the modification of the structure of this medicinal compound have revealed potential compounds with antinephritic [8] and anti-angiogenic [9, 10] properties in a given series as well as novel synthetic immunomodulators [11].In this report we continue our work studying the physicochemical and biological properties of 4-hydroxyquinol-2-ones and have investigated 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides 1 and their 4-bromo-substituted analogs 2. The target compounds (Tables 1-3) were prepared by amidation of the ethyl esters 3 with aniline and 4-bromoaniline respectively according to a previously developed method [12].It is known that 3-alkyl-, 3-phenyl-, and 3-alkoxycarbonyl-substituted 4-hydroxy-2-oxo-1,2-dihydroquinolines (including N-phenyl) are brominated by molecular bromine in glacial acetic acid at position 3 to give 3-bromo-3-R-2,4-dioxo-1,2,3,4-tetrahydroquinolines [13,14].However, we later showed that with completely anhydrous solvents and reagents the indicated reaction occurs differently with electrophilic attack exclusively at position 6 of the quinolone [15]. With the anilides 1 a still further possible center for halogenation occurs (the phenylamide ring).