Organic azides in heterocyclic synthesis, 11. Ring closure of 3‐acetyl‐4‐azido‐2‐quinolones to isoxazolo[4,3‐c]quinolones

Abstract

Thermolysis of the 3-acetyl-4-azido-2-quinolone 6, which was obtained from the corresponding 4-tosyloxy derivative 5, afforded the ring closed isoxazoloquinolone ? in good yield.The cyclization of ortho-substituted azido arenes and heteroarenes by thermo-or photolysis is a well-known reaction'). These reactions have been applied by us to some heterocyclic systems (e.g. coumarins, quinolines, pyrimidines and pyridazines) bearing aryl or benzyl groups in ortho position3). Another type of ortho substituents which should cyclize easily with azido groups are carbonyl groups as in acyl or cyano groups4).We studied the thermolysis of 4-azido-2-quinolones, which bear an acetyl group in the 3-position. According to the findings of Suschitzky and co-workers 5, also the influence of the ortho substituent on the thermolysis temperature was of interest.3-Acetyl-4-hydroxy-l-methyl-2(1H)-quinolone (3) was prepared by an improved two-step procedure developed for pyridones6) from N-methylaniline and diethyl malonate. By the addition of diphenyl ether the yield of the pyrone 2 increased from 55%7) to 66%. The degradation of 2 to the 3-acetylquinolone 3 was performed in 1,2ethanediol/aqueous sodium hydroxide during 1 h (instead of 24 h in aqueous sodium hydroxide solution7)) to yield the highly pure acetyl compound 3.The usually applied method for preparing 4-azidoquinolones proceeds via the corresponding 4-chloroquinoloness~. However, all attempts to convert the 4-hydroxyquinolone 3 into the 4-chloroquinolone 4 failed. Either no reaction took place or, under drastic conditions, the 3-acetyl group was cleaved to yield the 3-unsubstituted 4-hydroxy-1-methyl-2-quinolone.Another method to introduce the azido group is the conversion of the hydroxy group into the reactive tosyloxy group**). Direct tosylation of 3-acetyl-4-hydroxyquinolone 3 failed, but reaction of the sodium salt of 3 resulted in the formation of the desired 3acetyl-4-tosyloxyquinolone 5, a very reactive compound, which can

On the Energy Efficiency of Microwave‐Assisted Organic Reactions

“…120 8C) reaction mixture led to crystallization of the crude reaction product, which was subsequently collected by filtration to furnish the pyranoquinolone in 81 % yield and excellent purity (> 98 % by HPLC and 1 H NMR spectroscopy). To compare the energy efficiency of this microwave-assisted synthesis with the corresponding conventional preparation, [30,31] two additional control experiments on the same scale employing a similar experimental setup were performed, one in a conventional oil bath (3.3 L oil, maximum temperature 240 8C) and one employing a high-powered heating mantle (300 W, maximum temperature > 350 8C, no stirring). Confirming previous reports, [31] the formation of the pyranoquinolone in the comparatively inert oil bath with a temperature limit of 240 8C required 26 h to reach completion and provided the desired product in a moderate (46 %) yield.…”

“…To compare the energy efficiency of this microwave-assisted synthesis with the corresponding conventional preparation, [30,31] two additional control experiments on the same scale employing a similar experimental setup were performed, one in a conventional oil bath (3.3 L oil, maximum temperature 240 8C) and one employing a high-powered heating mantle (300 W, maximum temperature > 350 8C, no stirring). Confirming previous reports, [31] the formation of the pyranoquinolone in the comparatively inert oil bath with a temperature limit of 240 8C required 26 h to reach completion and provided the desired product in a moderate (46 %) yield. In contrast, the heating-mantle experiment at a maximum end temperature of 260 8C allowed us to more closely mimic the time-temperature profile followed in the microwave experiment and therefore also required a similar time period (120 min).…”

Novel heterocyclic derivatives of pyrano[3,2-c]quinolinone from 3-(1-ethy1-4-hydroxy-2-oxo-2(1H)-quinolin-3-yl)-3-oxopropanoic acid

“…For example, degradation of 1 in boiling 2N sodium hydroxide aqueous solution yielded 1-ethyl-3-acetyl-4-hydroxyquinolin-2(1H)-one through pyrone ring opening, followed by decarboxylation [11,12]. In continuation to previous research on 4-hydroxyquinolin-2(1H)-ones [13][14][15][16][17][18], the present paper reports the synthesis of the new 3-(1-ethy1-4-hydroxy-2-oxo-2(1H)-quinolin-3-yl)-3-oxo-propanoic acid (2) and the study of its chemical reactivity towards some ortho-hydroxyaldehydes and ortho-aminoaldehydes, in search of new quinolinone derivatives of potential biological activity.…”

Synthesis of Quinolin‐4‐yl Substituted Malonates, Cyanoacetates, Acetoacetates and Related Compounds.

“…These compounds were prepared from 3-acetyl-4-hydroxy-2(1H)-quinolones and tosylchloride according to ref. [11].…”