Novel Synthesis of Acylaminomethylene Meldrum's Acids and Their Thermolysis to 4-Methylthio-and 4-Amino-2-aryl-6H-1,3-oxazin-6-ones

Bismethylthiomethylene Meldrum's acid reacts with amides in the presence of potassium hydroxide to afford methylthioacylaminomethylene Meldrum's acid 5. Aminolysis of 5 gives aminoacylaminomethylene Meldrum's acids 7. Thermolysis of 5 and 7 supplies a novel synthetic method of 4-methylthio- and 4-amino-2-aryl-6H-1,3-oxazin-6-ones.     

4-Substituted-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones. III (2,3). Solvolytic-reductive transformation of 4-(2-keto)-benzoxazin-2-ones into oxazin-2-ones

A series of 4-(2-keto-substituted)-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones 1 (Table I) was synthesized by condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazin-2-ones 4 with ketones 5 having active alpha hydrogens. In the presence of alcoholic potassium borohydride, compounds 1 underwent reductive transacylation to give 1,3-oxazin-2-one derivatives 3 (Table III, a,b,c). When the other side of the ketone possessed substituents other than hydrogen, there were always also normal reduction products, i.e., secondary alcohols 2 (Table II) in addition to 3.     

On the synthesis of 5‐ethyl meldrum's acid

Reductive alkylation of Meldrum's acid with acetaldehyde can give, depending on the experimental conditions, either a new dimer (5‐[3‐(2,2‐dimethyl‐4,6‐dioxo‐1,3‐dioxan‐5‐yl)butyl]‐2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione) or ethyl Meldrum's acid (2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione). A best way to obtain this latter product is synthesis of 1‐ethoxyethylidene Meldrum's acid from reaction of Meldrum's acid with triethyl orthoacetate, followed by a sodium borohydride reduction.     

Reaction of 2,3-Dihydro-1,5-benzothiazepines and Phenylacetyl Chloride in the Presence of Triethylamine： A New Aspect on the Formation Mechanism of Dihydro-1,3-oxazin-4-one Derivatives

2a,4-Disubstituted 2,2a,3,4-tetrahydro-2-phenyl-1H-azeto[2,1-d][ 1,5]benzothiazepin-1-ones, as well as 2-substi-tuted 2,3-dihydro-3-phenylacetyl-2-styryl-benzothiazoles and 4a,6-disubstituted 3- .benzyl-4a,5-d/hydro-2-phenyl-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, were obtained from the reaction of 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepines with phenylacetyl chloride in the presence of triethylamine. The mechanism for the formation of 4a,5-dihydro-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, 2,3-dihydro-1,3-oxazin-4-one derivatives, was suggested.     

Studies on condensation of chlorocarbonyl phenyl ketene with <Emphasis Type="Italic">N</Emphasis>-unsubstituted amides: synthesis of some new 1,3-oxazin-6-ones

A series of 1,3-oxazin-6-one derivatives has been synthesized upon treatment of N-unsubstituted amides with chlorocarbonyl phenyl ketene under reflux in toluene for several minutes. In this simple way, 2,5-disubstituted derivatives of 1,3-oxazin-6-ones have been obtained in high yields.     

Electron ionization mass spectra of some 4β-phenyl-substituted cycloalkane-cis-fused 1,3-oxazin-2(3H)-ones, -2(3H)-thiones and 1,4-oxazepin-3(4H)-ones

The 70 eV mass spectra of 4β-phenyl-substituted cyclopentane- and cyclohexane cis-fused 1,3-oxazin-2(3H)-ones, the two related 2-thiones, 6,7-cis-trimethylene-5β-phenyl-1,4-oxazepin-3(4H)-one and its 2β-methyl derivative were recorded and their fragmentations examined by means of metastable ion analysis, collision induced dissociation technique and exact mass measurement. The fragmentation patterns of the 1,3-oxazin-2(3H)-ones were relatively simple: the favored formation of cycloalkene ions implied that a considerable proportion of the molecular ions might possess an enol structure. Changes in the size of the fused cycloalkane ring had little or no effect on the fragmentations. Instead, small changes in the heterocyclic part of the molecule caused remarkable effects on the fragmentation behavior. Compared to 1,3-oxazin-2(3H)-ones studied, both 1,3-oxazine-2(3H)-thiones and 1,4-oxazepin-3(4H)-ones showed much more complicated fragmentation patterns.     

Chemistry of oxalyl derivatives of methyl ketones. 40. Reaction of 5-aryl-2,3-dihydro-2,3-furandiones with aryl and aroyl cyanamides

Starting from 5-aryl-2,3-dihydro-2,3-furandiones and benzoyl cyanamide, 2-benzoylamino-6-aryl-1,3-oxazin-4-ones were obtained. It was shown that on reaction of o-chlorophenyl cyanamide with furandiones, 2-imino-3-(o-chlorophenyl)-5-phenacyliden-4-oxazolidones are formed which in acid medium rearrange to 3-(o-chlorophenyl)-5-phenacylideneimidazolidin-2,4-diones and on thermolysis in acid medium they form 2-(o-chloroanilino)-6-aryl-1,3-oxazin-4-ones.For Communication 39, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 166–169, February, 1985.     

Reactions of 2-alkylsulfanyl- and 2-alkoxy-4-hydroxy-6<Emphasis Type="Italic">H</Emphasis>-1,3-oxazin-6-ones with O-nucleophiles

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.     

Reactions of 2-acyl-1,3-indandiones with monosubstituted hydrazines and hydrazides

Methyl- and phenylhydrazines react with 2-(diphenylacetyl)-1,3-indandione ( 1 ) to yield respectively the 1-(methylhydrazone) and the 1-(phenylhydrazone) of 2-(diphenylacetyl)-1,3-indandione ( 2a and 2b ). In comparison, acetic and benzoic acid hydrazides react with 1 to give respectively the α-(acetylhydrazone) and the α-(benzoylhydrazone) of 2-(diphenylacetyl)-1,3-indandione ( 3a and 3b ). Cyclization of 2a and 2b gives 2,3-disubstituted indeno[1,2-c]pyrazol-4(2H)-ones ( 7a and 7b ). Cyclization of 3a and 3b , followed by methylation, gives 1-methyl- and 2-methyl-3-(diphenylmethyl)indeno[1,2-c]pyrazol-4(1 and 2H)-ones ( 9a and 9b ). 2-Isovaleryl-1,3-indandione reacts with phenylhydrazine to give directly 3-isobutyl-1-phenylindeno[1,2-c]-pyrazol-4(1H)-one ( 10 ).     

Reaction of difluorocarbene with 2H-azirines: generation and transformations of strained azomethine ylides -- aziriniodifluoromethanides

The reaction of difluorocarbene with azirines affords a new type of azomethine ylides, viz., strained aziriniodifluoromethanides. 1,3-Dipolar cycloadditions of ylides derived from 2-unsubstituted 3-arylazirines to dimethyl acetylenedicarboxylate and aldehydes give derivatives of 2,2-difluoro-1-azabicyclo[3.1.0]hex-3-ene-3,4-dicarboxylic acids and 1,4-oxazin-3(4H)-ones, respectively. Ylides derived from 2-mono- and 2,2-disubstituted azirines undergo isomerization to 2-aza-1,3-diene derivatives. 2,2-Difluoro-1-azabicyclo[3.1.0]hex-3-enes are transformed into 2-fluoropyridine derivatives in high yields and react with amines to give 2,4-diamino-1-azabicyclo[3.1.0]hex-2-ene derivatives.     

Synthesis of 2,7-disubstituted-5,6-dimethylpyrrolo-[2,3-d]-1,3-oxazin-4-ones as antifungal agents

A series of novel 5,6-dimethylpyrrolo[2,3-d]-1,3-oxazin-4-ones were synthesized from 2-amino-3-tert-butoxy-carbonyl-4,5-dimethylpyrroles. Two methods were used, cyclodehydration of 2-acylamino-3-carboxypyrroles with acetic anhydride and direct conversion of the 5,6-dimethylpyrrolo[2,3-d]-1,3-oxazin-2,4-diones to the title compounds with an anhydride directly providing the 2 substituent. Molecular modeling techniques revealed that these pyrrolo[2,3-d]oxazinones were rigid analogues of the allylamine antifungals. The compounds were tested for in vitro activity against Tricophyton and Scopulariopsis sp.     

New organic nitrates. II. Synthesis of 2H-pyrido[2,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazin-4(3H)-ones, 2H-thieno[2,3-e]-1,3-oxazin-4(3H)-ones and 2H-thieno[3,4-e]-1,3-oxazin-2,4(3H)-diones

The preparation and the physico-chemical characterization of 2H-pyrido[2,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazin-4(3H)-ones, 2H-thieno[2,3-e]-1,3-oxazin-4(3H)-ones and 2H-thieno[3,4-e]-1,3-oxazine-2,4(3H)-diones are reported.     

Synthesis of pyrazolo[1,5-a]pyrimidines in the reaction of 5-amino-3-arylpyrazoles with methoxymethylene meldrum's acid derivatives and thermolysis of their pyrazolylaminomethylene derivatives

A series of pyrazolo[1,5-a]pyrimidin-3-ones 3 was prepared from Meldrum's acid and 5-amino-3-arylpyrazoles 1 by cyclization in nitrobenzene of the corresponding 5-pyrazolylaminomethylene Meldrum's acid derivatives 2 . The structure of pyrazolo[1,5-a]pyrimidin-3-ones and their precursors were determined by nmr measurements.     

Heterocyclization of functionalized heterocumulenes with C,N-and C,O-binucleophiles: VI. Synthesis of carbofused 2,3-dihydro-1,3-oxazin-4-ones and 3,4-dihydro-1,3-oxazin-2-ones

Condensations of 1-phenyl-2,2,2-trifluoro-1-chloroethyl isocyanate and 1-chlorobenzyl isocyanate with cyclic 1,3-diketones yield respectively carbofused 2,3-dihydro-1,3-oxazin-4-ones and 3,4-dihydro-1,3-oxazin-2-ones.     

Hetero-diels-alder reaction of N-cyanoaniline and pyridinium cyano-(ethoxycarbonyl)methylide with aroylketenes generated in situ in thermolysis of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones

We have used thermolysis of 6-aryl-2,2-dimethyl-1,3-dioxin-4-ones in the presence of N-cyanoaniline, pyridinium cyano(ethoxycarbonyl)methylide, and 4-hydroxybenzonitrile to obtain the corresponding 6-aryl-2-phenylamino-1,3-oxazin-4-ones, pyridinium ethoxycarbonyl(4-oxo-6-aryl-4H-1,3-oxazin-2-yl)methylides, and p-cyanophenyl esters of 3-aryl-3-oxopropanoic acids. We present the results of a preliminary investigation of the biological activity of these compounds. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 764–768, May, 2006.     

Preparation of 5-sulfonylpyrimidines from β-keto, β-cyano-, and β-ethoxycarbonyl-β-sulfonylenamines

β-Keto-β-sulfonylenamines 2a,b reacted with benzamidine or guanidines to give 2,4-disubstituted 5-methanesulfonylpyrimidines 3a-d , whose methanesulfonyl groups were substituted by n-butyllithium or alkylmagnesium bromides to yield 2,4-disubstitued 5-alkylpyrimidines 6a-d. 2-Substituted 4-amino-5-sulfonylpyrimidines 7a,b, 8 and 2-substituted 5-benzenesulfonylpyrimidin-4-ones 9a,b were similarly obtained from β-cyano-β-sulfonylenamines 2c,d and β-ethoxycarbonyl-β-sulfonylenamine ( 2e ), respectively.     

A convenient synthesis of 1,3-oxazolidin-4-ones and 1,3-oxazin-4-ones

1,3-Oxazolidin-4-ones and 1,3-oxazin-4-ones were synthesized by formal cyclocondensation of imines with α- or β-hydroxy acids.     

Carbamoylation of B6 vitamins

The reaction of B₆ vitamins 1–3 with cyanate, in the presence of equivalent amounts of hydrochloric acid, yields different adducts according to the structure of the starting material. Regiospecific attack on the amino group or the phenolic hydroxy group was found for 2a,b and 3a,b , respectively. From the aldehydes 1a,b , the 2H-pyrido[3,4-e]-1,3-oxazin-2-ones 7a,b were obtained through an attack on both the phenolic and aldehyde group.     

Potentiometric study on acid properties of some 4-hydroxy-6H-1,3-oxazin-6-ones. Structure-biological activity relationship

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 pK _a 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.     

Eine überraschende Ringerweiterung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin zu 4,5-Dihydropyridin-2(3H)-on-Derivaten

An Unexpected Ring Enlargement of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine to 4,5-Dihydropyridin-2(3H)-one Derivatives The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1a ) and 4,4-disubstituted 2-(trifluoromethyl)-1,3-oxazol-5(4H)-ones 7 in MeCN at 70° afforded 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 10 (Scheme 4), whereas no reaction could be observed between 1a and 2-allyl-4-phenyl-2-(trifluoromethyl)-1,3-oxazol-5(2H)-one ( 8a ) or 4,4-dibenzyl-2-phenyl-1,3-oxazol-5(4H)-one ( 9 ). The formation of 10 is rationalized by a mechanism via nucleophilic attack of 1a onto 7 . The failure of a reaction with 9 shows that only activated 1,3-oxazol-5(4H)-ones bearing electron-withdrawing substituents do react as electrophiles with 1a . The amino-azirine 1a and 2,4-disubstituted 1,3-oxazol-5(4H)-ones 2b – e in refluxing MeCN undergo a novel ring enlargement to 4,5-dihydropyridin-2(3H)-ones 11 (Scheme 5). Several side products were observed in these reactions. Two different reaction mechanisms for the formation of 11 are proposed: either 1a undergoes a nucleophilic addition onto the open-chain ketene tautomer of 2 (Scheme 6), or 2 reacts as CH-acidic compound (Scheme 7).