Synthesis and fluorescence properties of novel benzo[a]phenoxazin-5-one derivatives

Thirteen, benzo[a]phenoxazin-5-one derivatives 3a-m were synthesized from 4-nitrosoaniline hydrochlorides 1a-m and ethyl 1,3-dihydroxynaphthoate 2 and their fluorescence properties were discussed in terms of the electronic effect of substituents. A coupling reaction was carried out with 6-carbethoxy-9-N-(2-hydroxyethyl)-N-methylamino-5H-benzo[a]phenoxazin-5-one (3k) and acetyl-DL-alanine to afford N-[(6-carbethoxy-5-oxo-5H-benzo[a]phenoxazin)-9-yl]-N-methylaminoethylene acetyl-DL-alanine ester (4).     

Synthesis of 11-aza-5H-benzophenoxazin-5-one and 11-Aza-5H-pyridophenoxazin-5-one derivatives

The 1,6-disubstituted- and 4,6-disubstituted-11-aza-5H-benzo[a]phenoxazin-5-one as well as 6-substituted-11-aza-5H-pyrido[a]phenoxazin-5-one derivatives were prepared by the condensation of 2-amino-3-hydroxypyridine with 5-substituted-2,3-dihalogeno-1,4-naphthoquinones and 6,7-dibromo-5,8-quinolinequinone respectively. The resulting compounds were subjected to reduction, acetylation, dehalogenation and reaction with aniline.     

The photochemical reactions of 5H-benzo[a]phenoxazin-5-one with alkylthiols and thiophenol

6-Alkylthio- and 6-phenylthio-5H-benzo[a]phenoxazin-5-ones have been synthesized by the photochemical reaction of 5H-benzo[a]phenoxazin-5-one with alkylthiols and thiophenol.     

Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

Synthesis of some 5H-benzo[a]phenoxazin-5-one derivatives

The substituted 6-bromo and 6-chloro-5H-benzo[a]phenoxazin-5-ones, prepared by condensation of substituted 2-aminophenols with 2,3-dibromo or 2,3-dichloro-1,4-naphthoquinone in methanolic potassium hydroxide solution, have been dehalogenated to substituted 5H-benzo[a]phenoxazin-5-ones in the presence of sodium hydrosulfite dissolved in aqueous pyridine under nitrogen atmosphere.     

Synthesis of pyrido[2,3-d]pyrimidin-4-one derivatives

This paper describes one-pot synthesis of 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidin-5-one 4 , 5H-dipyri-do[1,2-a:3′,2′-e]pyrimidin-5-one 10 and 5H-pyrido[3,2-e]pyrimido[1,2-a]pyrimidin-5-one 15 and some of their derivatives, starting with 2-chloro-3-pyridine carboxilic acid 1. Compounds 4 and 10 reacted with phosphorus pentasulfide to give the respective 5-thione analogues, 5 from 4 and 11 from 10 . Boiling the 5-thione derivatives with hydrazine hydrate, the respective 5-hydrazono derivatives 6 from 5 and 12 from 11 were obtained. The 5-acetyl hydrazono, 7 , and the 5-isopropylidenehydrazono, 8 , derivatives were also prepared from 6 , and the 5-propionylhydrazono derivatives, 13 , from 12 . Compound 4 reacted with hydrazine to give an adduct with two molecules of hydrazine and the probable structure 16 . Treating this adduct with acetone a monohydrazone 17 was obtained. Boiling a suspension of this adduct in DMF, it gave 6,10-dihydro-6H-pyrido[3′,2′:5,6]pyrimido[2,1-c][1,2,4]triazin-5-one 20 .     

Synthesis of 6-amino-2-aryl-1,2-dihydro-3H-pyrido[2,3-d]pyrimidin-4-one derivatives

This paper reports the synthesis of new pyrido[2,3-d]pyrimidin-4-one derivatives as diuretic agents. Starting with 1,2-dihydro-5-nitro-2-oxo-3-pyridinecarboxylic acid 1 , ethyl 2-ethoxy-5-nitro-3-pyridincarboxylate 4 was obtained. Compound 4 reacts with ammonia, methylamine or S-methylpseudothiourea to give the respective 2-amino-5-nitro-3-pyridinecarboxamide derivatives 5 and 6 or 2-methylthio-6-nitro-3H-pyrido[2,3-d]pyrimidin-4-one 8. Treating carboxamide 5 with arylaldehydes and zinc dichloride, new 2-aryl-1,2-dihydro-6-nitro-3H-pyrido[2,3-d]pyrimidin-4-ones 9 were synthetised. These compounds reduced with iron(II) hydroxide gave 6-amino-2-aryl-1,2-dihydro-3H-pyrido[2,3-d]pyrimidin-4-ones 10 as expected.     

Simple synthesis of 6-alkyl-5H-benzo[a]phenoxazin-5-ones

6-Alkyl-5H-benzo[a]phenoxazin-5-ones were prepared by the reaction of 5H-benzo[a]phenoxazin-5-one with carboxylic acid in the presence of silver ion and peroxydisulfate.

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Eine einfache Synthese von 6-Alkyl-5H-benzo[a]phenoxazin-5-onen (Kurze Mitteilung)

Zusammenfassung 6-Alkyl-5H-benzo[a]phenoxazin-5-one wurden mittels Reaktion von 5H-Benzo[a]phenoxazin-5-onen mit Carbonsäuren in Gegenwart von Silberionen und Peroxydisulfat dargestellt.

     

Synthesis of azolo[a]pyridines from 5-(bromomethyl)hept-4-en-3-one and 5-bromopent-3-en-2-one derivatives

Alkyl derivatives of 1H-imidazo[1,2-a]pyridin-4-ium, 5H-pyrido[1,2-a]benzimidazol-10-ium, 1H-[1,2,4]-triazolo[4,3-a]pyridin-4-ium, and 3-methylthiazolo[3,2-a]pyridin-4-ium bromides were obtained in two stages from (4Z)-5-(bromomethyl)-2,2,6,6-tetramethylhept-4-en-3-one, 5-bromo-4-methylpent-3-en-2-one, or (3E)-5-bromopent-3-en-2-one by alkylation of 1-alkyl-1H-imidazoles, 1-alkyl-1H-benz-imidazoles, 1-methyl-1H-1,2,4-triazole, and 4-methylthiazole and subsequent cyclization of the quaternary azolium salts in the presence of bases.     

The reaction of 2-acetoacetamidopyridines with phosgene. A route to novel 3-Acetyl-2-chloro-4H-pyrido[ 1,2-a] pyrimidin-4-ones

2-(Acetoacetamido)pyridine, 1 , and its 5-methyl derivative, 2 , with phosgene, gave 3-acetyl-2-chloro-4H-pyrido[1,2-a]pyrimidin- 4 -one, 5 , and 3-acetyl-2-chloro-7-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one, 6 , respectively. The structures of these compounds followed from their elemental analyses, and interpretations of their uv, ir, pmr, and X-ray spectra. An alternative route to 5 and 6 , which sought first to react 1 and 2 with methyl - and benzyl chloroformates, was unsuccessful, and led, instead, to elimination of the acetoacetyl group with concomitant formation of the carbamate derivatives, 10 and 11 .     

Electronic structure of 4H-pyrido[1,2-a]pyrimidin-4-ones

The characteristic features of ir and uv spectra of 43 4H-pyrido[1,2-a]pyrimidin-4-one derivatives with electron donor or acceptor groups in position 3, and positions 6, 7, 8, or 9, respectively, have been systematically studied. On the basis of the spectra some conclusions have been drawn for the molecular structure. The negative solvent effect of the lowest-energy π → π* transition is investigated by the PPP method.     

8,9,10-Trifluoro-6-oxo-6H-pyrido[1,2-a]quinoline-5-carbonitrile in the synthesis of novel 1-heteryl-3,3-dimethyl-3,4-dihydroisoquinolines

3,4-Dihydroisoquinolines containing the 8,9,10-trifluoro-6H-pyrido[1,2-a]quinolin-6-one substituent in position 1 were obtained by three-component reactions between arenes, isobutyraldehyde, and 8,9,10-trifluoro-6-oxo-6H-pyrido[1,2-a]quinoline-5-carbonitrile in H2SO4.     

The photochemical synthesis of 6-acyl-5H-benzo[a]phenoxazin-5-ones

6-Acyl-5H-benzo[a]phenoxazin-5-ones were prepared by the photochemical reaction of 5H-benzo[a]phenoxazin-5-one with aldehydes.

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Die photochemische Synthese von 6-Acyl-5H-benzo[a]phenoxazin-5-one (Kurze Mitteilung)

Zusammenfassung Die Titelverbindungen wurden mittels photochemischer Reaktion von 5H-Benzo[a]phenoxazin-5-onen mit Aldehyden hergestellt.

     

Synthesis and anticonvulsant activities of 5-(2-Chlorophenyl)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepines

A group of 5-(2-chlorophenyl)-10-(substituted)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepines 7a-c were synthesized by the acid catalyzed reaction of 5-(2-chlorophenyl)-2-hydrazino-3H-pyrido[3,4-e]-[1,4]diazepine ( 6 ) with either trimethyl orthoformate, triethyl orthoacetate or triethyl orthobenzoate, respectively. 5-(2-Chlorophenyl)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepine ( 7a ) and 5-(2-chlo-rophenyl)-10-methyl-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepine ( 7b ) exhibited good anticonvulsant activity in the subcutaneous metrazol anticonvulsant screen which serves as a model for absence (petit mal) epilepsy.     

Syntheses of 10-Oxo-10H-pyrido[1,2-a]thieno[3,4-d]pyrimidines and 10-Oxo-10H-pyrido[1,2-a]thieno[3,2-d]pyrimidines from methyl tetrahydro-4-oxo-3-thiophenecarboxylate and methyl tetrahydro-3-oxo-2-thiophenecarboxylate,respectively

A general synthesis of 10-Oxo-10H-pyrido[1,2-a]thieno[3,4-d]pyrimidines and 10-Oxo-10H-pyrido[1,2-a]-thieno[3,2-d]pyrimidines is described. Methyl tetrahydro-4-oxo-3-thiophenecarboxylate ( 13 ) was condensed with 6-aminonicotinic acid ( 18 ) to give 3,10-dihydro-10-oxo-1H-pyrido[1,2-a]thieno[3,4-d]pyrimidine-7-carboxylic acid ( 19 ). Treatment of 19 successively with chlorotrimethylsilane, N-chlorosuccinimide and water gave 10-oxo-10H-pyrido[1,2-a]thieno[3,4-d]pyrimidine-7-carboxylic acid ( 17 ). Methyl tetrahydro-3-oxo-2-thiophenecarboxylate ( 21 ) was converted to 10-oxo-10H-pyrido[1,2-a]thieno[3,2-d]pyrimidine-7-carboxylic acid ( 25 ) by an analogous route.     

Unexpected formation of a 11H-pyrido[2,1-b]quinazolin-11-one derivative from 5,11-dihydro-6H-pyrido[2,3-b]-1,4-benzodiazepin-6-one

The unexpected formation of 11H-pyrido[2,1-b]quinazolin-11-one derivative 6 from 5,11-dihydro-6H-pyrido[2,3-b]-1,4-benzodiazepin-6-one (2) has been observed. Its structure 6 was determined by X-ray crystallography. Detailed nmr study provided a complete set of proton and carbon-13 nmr parameters of compound 6 in solution.     

Catalyst- and Oxidant-Free Electrochemical Regioselective Halogenation and Trifluoromethylation of 4H-Pyrido[1,2-a]pyrimidin-4-ones

The catalyst-free electrochemical halogenation and trifluoromethylation of 4H-pyrido[1,2-a]pyrimidin-4-ones was realized under external-oxidant-free conditions. This strategy provides an easy and green access to functionalized new 4H-pyrido[1,2-a]pyrimidin-4-one derivatives with broad scope, good functional group tolerance and high regioselectivity.     

Synthesis of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives

The reaction of 2-aminothiazoles with ethyl acetoacetate in acetic or polyphosphoric acid gave a series of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives which were nitrated with a mixture of nitric and sulfuric acid to 6-nitro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-ones, and the latter were reduced to the corresponding amines.     

Benzimidazole condensed ring systems. 2. New synthesis of substituted 1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitriles and related derivatives

The synthesis of some 3-substituted and 2,3-disubstituted-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbo-nitriles 5,6 by fusing 1H-benzimidazole-2-acetonitrile 1 with some β-keto esters 2,4 in the presence of ammonium acetate or with ethyl β-aminocrotonate 3 is described. The tricyclic compounds were converted to their N-5 methyl of N-5 ethyl derivatives 8,9. Vilsmeir-Haack formylation of 3-methyl-1-oxo-1H,5H-pyrido[1,2-a]-benzimidazole-4-carbonitrile 5a afforded its 2-formyl derivative 10. Chlorination of 5 and 6 with phosphorus oxychloride yielded the respective 1-chloropyrido[1,2-a]benzimidazole-4-carbonitriles 11,12 which were utilized to prepare the 1-azido, 1-amino, 1-piperidino and 1-methoxy derivatives of the ring system. Compound 11a exhibited strong in vitro activity against S. aureus. Four compounds were screened against P-388 lymphocytic leukemia in mice but were inactive.     

Oxidation of 3-hydroxykynurenine. A reexamination

The oxidation mixture of 3-hydroxykynurenine ( 1 ), treated with aqueous acetic anhydride and, subsequently, with acidic methanol, yields the 1-hydroxy-3-carbomethoxy-5-methoxy-11-(β-aspartoyl-N-acetyl-methyl ester)pyrido[3,2-a]phenoxazine ( 5 ), the 1-hydroxy-11-(β-aspartoyl-N-acetyl-methyl ester)-5.H-pyrido[3,2-a]-phenoxazin-5-one ( 6 ), the 1-methoxy-11-(β-aspartoyl-N-acetyl-methyl ester)-5H-pyrido[3,2-a]phenoxazin-5-one ( 6a ), the l,5-dimethoxy-11-(β-aspartoyl-N-acetyl-methyl ester)pyrido[3,2-a]phenoxazine ( 7 ) and the 1-methyl-1(1′-[11-(β-aspartoyl-methyl esterimino)]ethenyl)ketal-1H,5H-pyrido[3,2-a]phenoxazin-5-one ( 8 ). A probable scheme, for the compound formation, is reported.