The reaction of carboxylic acid amides with malonyl chloride in acetonitrile or tetrahydrofuran without heating leads to the formation of previously unknown 2-substituted 5-hydroxypyrano[2,3-d][1,3]oxazines. The structure of the obtained compounds was established by high resolution mass spectrometry, NMR spectroscopy, and X-ray analysis.

4-Hydroxy-6H-1,3-oxazin-6-ones with a coumarin fragment in position 2 of the oxazine ring were synthesized. Their hydrolysis, alcoholysis, and hydrazinolysis afforded a number of new coumarin derivatives containing malonamic acid and 1,2,4-triazole residues. The low stability of the title compounds toward oxygencentered nucleophiles was interpreted by quantum chemical calculations.

2-(2-Furyl)- and 2-(2-thienyl)-5-alkyl-4-hydroxy-6 H -1,3-oxazin-6-ones react with guanidine in methanol in the presence of an equimolar amount of sodium methoxide to give previously unknown sodium 4-amino-6-hetaryl-1,3,5-triazin-2-ylacetates. The reactions of 2-(2-furyl)- and 2-(2-thienyl)-5-phenyl-4-hydroxy-6 H -1,3-oxazin-6-ones with guanidine under analogous conditions are accompanied by decarboxylation, yielding 4-benzyl-6-hetaryl-1,3,5-triazin-2-amines. The corresponding decarboxylation products are also obtained by treatment of sodium 2-(4-amino-6-hetaryl-1,3,5-triazin-2-yl)propionates with aqueous HCl.

Reactions of 2-alkylsulfanyl- and 2-alkoxy-4-hydroxy-6H-1,3-oxazin-6-ones with oxygen-centered nucleophiles were studied. 2-Alkoxy-4-hydroxy-6H-1,3-oxazin-6-ones reacted with water and alcohols to give the corresponding alkyl 3-amino-3-oxopropanoates as a result of opening of the oxazine ring at the C6-O bond, whereas their 2-alkylsulfanyl analogs turned out to be stable toward O-nucleophiles. The different reactivities of the title compounds were interpreted in terms of quantum-chemical calculations of their electronic structure.

Aromatic and heteroaromatic acid hydrazides reacted with oxalyl chloride in benzene or chloroform to give previously unknown 2-aryl(hetaryl)-4H-1,3,4-oxadiazine-5,6-diones whose structure was confirmed by the NMR, IR, and mass spectra. According to the spectral data and the results of quantumchemical calculations, the products exist mainly in the lactam form.

The reaction of methyl thiocarbamate with malonyl dichloride at low temperatures provides an N-substituted thiocarbamate, whereas prolonged boiling in high-boiling solvents gives rise to 4-hydroxy-2-(methylsulfanyl)-6H-1,3-oxazin-6-one that was also prepared by treatment of the N-substituted thiocarbamate with malonyl chloride in toluene and chlorobenzene.

4-Hydroxy-6H-1,3oxazin-6-ones exhibit properties of weak OH acids. These compounds are readily methylated with diazomethane to give the corresponding 4-methoxy derivatives. According to the potentiometric titration data, the pKa values of 2-methoxy-and 2-methylsulfanyl-substituted 4-hydroxy-6H-1,3-oxazin-6-ones range from 7.45 to 8.42, depending on the substituent in position 5 of the heteroring. 4-Hydroxy-6H-1,3-oxazin-6-ones in biological media exist mainly in the neutral form.

Phenylmalonyl dichloride reacted with 3-phenylpropynamide to give 4-hydroxy-5-phenyl-2-phenylethynyl-6 H -1,3-oxazin-6-one. Treatment of the latter with hydrazine afforded 3,5-disubstituted 1,2,4-triazole. Reactions of 4-hydroxy-5-phenyl-2-phenylethynyl-6 H -1,3-oxazin-6-one with methanol and ethanol led to formation of the corresponding malonamic acid esters. The structure of the products was proved by the 1 H and 13 C NMR and IR spectra, quantum-chemical calculations (PM3, MNDO, MINDO3), and some chemical transformations.

Alkyl carbamates and S-alkyl thiocarbamates react with substituted malonyl dichlorides in boiling benzene to give the corresponding 2,5-substituted 4-hydroxy-6H-1,3-oxazin-6-ones. The reaction of S-methyl thiocarbamate with unsubstituted malonyl dichloride in boiling diethyl ether or benzene leads to formation of S-methyl (3-methylsulfanylaminocarbonyl-3-oxopropionyl)thiocarbamate and is not accompanied by cyclization, whereas in boiling toluene 4-hydroxy-2-methylsulfanyl-6H-1,3-oxazin-6-one is obtained.

The review summarizes published data on the methods for preparation, chemical properties, and biological activity of 4-hydroxy-2H-pyran-2-ones and their derivatives.

Methylmalonyl dichloride reacts with (2E)-3-phenylacrylamides and (2E)-3-(2-furyl)acrylamide to give the corresponding E-isomeric 2-substituted 4-hydroxy-5-methyl-6H-1,3-oxazin-6-ones. The reaction of methylmalonyl dichloride with acrylamide afforded N-(3-chloropropionyl)-2-methylmalonamic acid. The structure of the products was confirmed by the 1H and 13C NMR, IR, and UV spectra.

4-Hydroxy-5-methyl(phenyl)-2-styryl-6H-1,3-oxazin-6-ones react with hydrazine and phenylhydrazine to give the corresponding 3,5-substituted triazoles. Treatment of the title compounds with ethanol and methanol leads to formation of N-cinnamoylmalonamates. The structure of the products was confirmed by the IR and 1H and 13C NMR spectra.

Alkoxy(alkylthio)-4-hydroxy-2H-pyran-2-ones readily react with electrophiles to give substitution products at C3. Hard electrophilic reagents replace hydrogen both in position 3 and in position 5 of the pyran ring. Methylation of 6-alkoxy(alkylthio)-4-hydroxy-2H-pyran-2-ones with diazomethane leads to formation of O- and N-methyl derivatives.

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6-Alkoxy-2-aryl-4H-1,3-oxazin-4-ones 1a-e react with hydrazine (2a) and phenylhydrazine (2b) with ring opening at the C-2-O followed by recyclization to 1,2,4-triazole-5-acetic acid esters 3a-e. Reactions of the title compounds with unsymmetrical dimethylhydrazine 2c led to formation of 2-substituted 4-hydroxyimidazole-5-carboxylates 5a-c.