4-Hydroxy-2-quinolones. 107. Reaction of triethyl methanetricarboxylate with indoline

Abstract

Keywords: amides of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids, heterocyclic derivatives of tricarbonylmethane, ethyl esters, X-ray structural analysis, thermolysis.The condensation of N-substituted anilines with a double or triple excess of methanetricarboxylic acid triethyl ester is used as one of the variants of the synthesis of ethyl esters of 1-substituted 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids [2,3]. We have shown in the example of indoline [4] and diphenylamine [5] that this reaction may also be fairly effectively carried out at an equimolar ratio of reactants, and the obtained 3-ethoxycarbonyl-4-hydroxy-2-oxoquinolines are best isolated and purified as the corresponding 4-O-sodium salts.On repeating the described method with indoline 1 many times it was noted that occasionally after treatment of the reaction mixture with aqueous Na 2 CO 3 solution, a portion of the obtained product remains insoluble. The original hypothesis that the isolated substance is a secondary acyclic methanetri-N-(indolin-1-yl)carboxamide is not justified since in its 1 H NMR spectrum there are two ethoxy groups (judging by the integral intensity of the signals). After recrystallization from ether monocrystals were successfully obtained, X-ray structural analysis of which gave the unequivocal answer that the sample investigated is the diethyl ester of 2-(indoline-1-carbonyl)malonic acid (2). The indoline fragment of this compound is planar with a precision of 0.01 Å (Fig.

4-Hydroxy-2-quinolones 120. Synthesis and structure of ethyl 2-hydroxy-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylate

“…Since these occur in the unassigned spectrum at 90.23 and 159.90 ppm the first must be the C (3) carbon atom and the second C (2) . 735 The 13 C NMR spectra of esters 1a-e also proved to be similar and a detailed study showed that the C (2) and C (9) signals had a width 3-4 time greater than the width of the remainder. These signals correspond to the carbon atoms placed close to the N (1) atom.…”

“…It was not possible to avoid formation of pyridyl-2-amide 3a in any of the experiments. However, this is a direct result of the direct amidation of the initially formed heterocyclic ester 1a by 2-aminopyridine since, in the first place amide 3a is separated even when carrying out the reaction in the comparatively low boiling toluene and, in the second, a thermal intramolecular cyclization of the intermediate ethyl bis(pyridin-2-ylcarbamoyl)acetate needs much more forcing conditions [9]. None the less, exchange of bromobenzene for xylene leads to some increase in the yield of the target ester 1a and simultaneous lowering of the amount of the unwanted pyridyl-2-amide 3a.…”

4-Hydroxy-2-quinolones. 118. Synthesis, structure, and chemical properties of 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo-[3,2-a]quinoline-4-carboxylic acid and its ethyl ester

“…However, the presence of a more powerful nucleophile in the structure of this intermediate (the bipolar 1,4-dihydro form 13, whose formation from 4-hydroxy-2-quinolinones has been noted by us before [8,9]) leads to the fact that the reaction finishes with heterocyclization. The significant factors responsible for such a reaction course are undoubtedly the size of the ring formed and the extreme convenience of the spatial positioning of the two reaction centers for its closing.…”

Improved synthesis, spectral characteristics and spatial structure of ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate

“…Сейчас найдено, что лучшие результаты могут быть достигнуты при использовании триэтилметантрикарбокси-лата в качестве ацилирующего и конденсирующе-го агента, а также высококипящего теплоноси-теля одновременно, что позволяет не только зна-чительно упростить его регенерацию, но и прак-тически полностью избежать нежелательного обра-зования 2-гидрокси-4-оксо-N-(пиридин-2-ил)-4Н-пиридо[1,2-а]пиримидин-3-карбоксамидов. Для подавления побочных реакций важен также и порядок введения исходных веществ в реакцию: вместо обычного постепенного нагревания ре-акционной смеси с последующим ее кипячени-ем, способствующим формированию триамидов метантрикарбоновой кислоты [23], следует к уже горячему триэтилметантрикарбоксилату прибав-лять раствор аминопиридина в триэтилметан-трикарбоксилате. На примере синтеза этилово-го эфира 2-гидрокси-8-метил-4-оксо-4Н-пиридо [1,2-а]пиримидин-3-карбоновой кислоты (1) по-казано, что такая несложная в исполнении моди-фикация позволяет получать целевой продукт с более высоким выходом и чистотой.…”