Regioselective synthesis of pyrrolin-3-ones and 2,3,4,5-tetrahydro[1,3]-oxazines from N-vinylic amidines

Achiral and optically active N-vinylic amidines are obtained by simple addition of amidines to acetylenic esters. Thermal intramolecular cyclization of these substrates containing a carboxylate group in position 3 gives pyrrolin-3-ones. The enaminone character of these compounds towards propargyl bromide, diethyl azodicarboxylate, diethyl acetylenedicarboxylate, ethyl propiolate and phenyl isocyanate is studied and functionalized pyrrolin-3-one derivatives are obtained. The reaction of the pyrrolinones prepared with diethyl ketomalonate leads to new 1,3-oxazine derivatives.     

A rapid and direct access to symmetrical/unsymmetrical 3,4-diarylmaleimides and pyrrolin-2-ones

1,8-Diazabicyclo[5.4.0]undec-7ene (DBU) facilitated the oxidative cyclization of phenacyl amide in the presence of atmospheric oxygen under environmentally friendly conditions. The reaction has been studied under various conditions and a plausible mechanism is proposed. This ‘green’ reaction proceeds via intramolecular ring closure of the amide followed by subsequent reaction with molecular oxygen where DBU played a crucial role. A variety of phenacyl amides were treated with DBU in acetonitrile under an oxygen atmosphere to give the symmetrical/unsymmetrical 3,4-diarylsubstituted maleimides in good yields. Corresponding pyrrolin-2-ones however, were obtained in good to excellent yields when K₂CO₃ was used in place of DBU affording a practical synthesis of these compounds of potential biological interest.     

A substituent-controlled general approach to access arylated pyran-2-ones and pyrano[3,4-c]pyran-1,8-diones

2H-Pyran-2-ones are useful precursors for the synthesis of various aromatic and heterocyclic compounds. In this Letter, we describe substituent-controlled direct access to functionalized 4-(2-oxo-1,2-diarylethyl)-5,6-diaryl-pyran-2-ones by stirring a mixture of 3-cyano-5,6-diaryl-2H-pyran-2-ones and functionalized deoxybenzoins through an unusual decyanation reaction. Under similar reaction conditions, the reactions of 3-carbomethoxy-5,6-diaryl-2H-pyran-2-ones with either substituted acetophenones or deoxybenzoins led to the synthesis of pyrano[3,4-c]pyran-1,8-diones in excellent yields.     

Synthesis of arylidene derivatives of N-unsubstituted pyrrolin-2-ones

5-Alkyl(aryl)-3-arylidene-3H-pyrrolin-2-ones were synthesized by ammonolysis of their O-heteroanalogs or by the reactions of 5-alkyl(aryl)-3H-pyrrolin-2-ones with aromatic aldehydes. The structures of the compounds obtained were confirmed by ¹H NMR spectra.     

Photoinduced Regioselective Chalcogenation and Thiocyanation of 4H-Pyrido[1,2-a] pyrimidin-4-ones Under Benign Conditions

A lenient approach for regioselective C3−H chalcogenation and thiocyanation of 4H-pyrido[1,2-a] pyrimidin-4-ones is developed using visible light photocatalysis. This operationally straightforward method furnishes a broad array of C-3, Ar−S/Ar−Se and -SCN functionalized derivatives in moderate to high yields. This protocol employs visible light as an environmentally friendly energy source, cost effective inorganic persulfate-based oxidant and easily procurable dichalcogenides for regioselective C−H chalcogenation of the substrate at room temperature. Further, regioselective thiocyanation of 4H-pyrido[1,2-a] pyrimidin-4-ones was also developed. Mechanistic path for these transformations has been proposed based on light on/off and Stern-Volmer studies as well as quantum yield calculations.     

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.     

The synthesis of methyl 2-(benzyloxycarbonyl)amino-3-dimethylaminopropenoate. The synthesis of trisubstituted pyrroles, 3-amino-2H-pyran-2-ones,fused 2H-pyran-2-ones and 4H-pyridin-4-ones

Methyl 2-(benzyloxycarbonyl)aimno-3-dimemylaminopropenoate ( 2 ) was prepared from methyl N-(benzyloxycarbonyl)glycinate ( 1 ) and t-butoxybis(dimethylamino)methane, and used as a reagent for preparation of substituted 3-(benzyloxycarbonyl)amino-4H-quinolizin-4-ones 5 and 6 , ?2H-pyran-2-ones 17–19 , ?2H-1-benzopyran-2-ones 28–31 , and -naphthopyrans 32–35 , ?2H-pyrano[3,2-c]pyridine-2,5-dione 46 , -pyrano-[4,3-b]pyran-2,5-dione 47 , -pyrano[3,2-c]benzopyran-2,5-dione 48 , -pyrano[2,3-c]pyrazol-6-ones 49 and 50 , -pyrano[2,3-d]pyrirnidin-7-ones 51 and 52 derivatives. In the reaction of 2 with 1,3-diketones trisubsti tuted pyrroles 14–16 were formed. Selective removal of benzyloxycarbonyl group was achieved by cat alytic transfer hydrogenation with Pd/C in the presence of cyclohexene to afford free 3-amino compounds 7 , 8 , 20 , 36–38 and 53–57 in yields better than 80%.     

Fused Polycyclic Nitrogen-Containing Heterocycles: IX. Oxidative Fusion of Imidazole Ring to 3-Benzoylquinoxalin-2-ones

3--Chlorobenzyl- and 3-benzoylquinoxalin-2-ones react with benzylamine in DMSO to give intermediate 3-(-benzyliminobenzylidene)quinoxalin-2-one which is capable of existing in several tautomeric forms. The subsequent oxidative cyclocondensation leads to imidazo[1,5-a]quinoxalin-4-one. This new procedure for building up imidazo[1,5-a]quinoxalin-4-one system has been applied to the synthesis of various bis(imidazo[1,5-a]quinoxalin-4-ones).     

Angular Regioselectivity in the Reactions of 2-Thioxopyrimidin-4-ones and Hydrazonoyl Chlorides: Synthesis of Novel Stereoisomeric Octahydro[1,2,4]triazolo[4,3-a]quinazolin-5-ones

The regioselective synthesis of cis and trans stereoisomers of variously functionalized octahydro[1,2,4]triazolo[4,3-a]quinazolin-5-ones was performed. The 2-thioxopyrimidin-4-ones used in the synthesis reacted with hydrazonoyl chlorides in a regioselective manner to produce the angular regioisomers [1,2,4]triazolo[4,3-a]quinazolin-5-ones rather than the linear isomers [1,2,4]triazolo[4,3-a]quinazolin-5-ones. The synthesis process took place with electronic control. The angular regiochemistry of the products was confirmed by X-ray experiments and two-dimensional NMR studies.     

1,2,4-Triazines. 8. Reduction of 4-methyl-1,2,4-triazin-5(4H)-ones with sodium borohydride. Regioselective preparation of dihydro-1,2,4-triazin-5(4H)-ones

Reduction of 3-methylthio-1,2,4-triazin-5(4H)-one ( 1a ) with sodium borohydride afforded 3-methylthio-1,6-dihydrotriazin-5(4H)-one ( 2b ) selectively. 3-Methylthio-6-t-butyl-1,2,4-triazin-5(4H)-one ( 1d ) reacted with sodium borohydride to give mainly 6-t-butyl-2,3-dihydro-1,2,4-triazin-5(4H)-one ( 3d ). The reaction of various 4-methyl-1,2,4-triazin-5(4H)-ones with sodium borohydride and the influence of bulkiness and electronic effect of the substituents at the 3- and 6-positions upon the product ratio, are also discussed.     

Metal-Free,Photoredox-Catalyzed Synthesis of Quinazolin-4(3H)-ones and Benzo[4,5]imidazo[1,2-c]quinazolines Using Trialkylamines as Alkyl Synthon

Highly functionalized quinazolin-4(3H)-ones were synthesized from reactions of N-aryl-2-aminobenzamides with trialkylamines under photocatalytic conditions by using eosin Y (EY) as a catalyst. The reaction proceeds under mild conditions in aqueous acetonitrile and has a broad substrate scope. Mechanistic studies disclosed the electron-donor nature of the intermediate 2,3-dihydroquinazolin-4(1H)-one ( 3’ ) in the photocatalytic cycle to afford the 2,3-disubstituted-quinazolin-4(3H)-ones ( 3 ). This methodology has been extended to synthesize benzo [4,5] imidazole[1,2-c] quinazolines and 3 aa on a large scale. Furthermore, the synthesis of potent central nervous system depressant (CNS) drug molecules such as methaqualone ( 3 la ) and mecloqualone ( 3 pa ) was also achieved successfully.     

Synthesis of some 5-Aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones from benzoxepinoisoxazolone and benzocycloheptaisoxazolone derivatives

Some 5-aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones were synthesized by hydrogenolytic cleavage of the isoxazole ring of 4-aryl-3-oxo-3,3a,4,10-tetrahydro[1]-benzoxepino[3,4-c]isoxazoles or 4-aryl-3-oxo-3a,4,9,10-tetrahydro-3H-benzo[4,5]cyclohepta[1,2-c]isoxazoles which in turn were prepared from ethyl 3-oxo-4-phenoxybutanoate or ethyl 3-oxo-5-phenylpentanoate by simple methods.     

Configurational and conformational aspects of some 5-methylenedisubstituted-3-pyrrolin-2-ones

The influence of the disubstitution at the exocyclic carbon atom of 5-methylene-3-pyrrolin-2-ones upon the configurational and conformational equilibria is studied. The results obtained confirm and extend the observations reported in the literature about the factors determining the configurational and conformational equilibria in monosubstituted systems, i.e.: 5-arylmethylene-3—pyrrolin-2-ones and 5(1H)-pyrromethenones.

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Zur Konfiguration und Konformation von einigen 5-Methylen-disubstituierten-3-pyrrolin-2-onen

Zusammenfassung Es wird der Einfluß der Disubstitution des exocyclischen C-Atoms von 5-Methylen-3-pyrrolin-2-onen auf das Konfigurations- und Konformationsgleich-gewicht untersucht. Die erhaltenen Resultate stehen im Einklang mit der Literatur, die sich auf monosubstituierte Verbindungen [5-Arylmethylen-3-pyrrolin-2-one, 5 (1H)-Pyrromethenone und strukturverwandte Gallenpigmente] beziehen, und vertiefen das Verständnis der Faktoren, die für diese Gleichgewichte maßgebend sind.

     

Novel heterocycles derived from substituted aroylthioureas: Synthesis of 3, l-benzothiazin-4-ones,thieno[3,2-d][1,3]thiazin-4-ones and 1,2,4-thiadiazolo[2,3-a][3,1]benzothiazin-5-ones

A series of heterocyclic aroylthioureas has been prepared and investigated as starting materials for ring closure reactions. The formation of several new 3,1-benzothiazin-4-ones and thieno[3,2-d][1,3]thiazin-4-ones (via cyclocondensation reactions) is reported. Oxidative cyclizations were carried out to produce methyl benzothiazole-4-carboxylates (via formation of an S-C bond) as well as 1,2,4-thiadiazolo-[2,3-a][3,1]benzothiazin-5-ones (via formation of an S? N bond).     

Synthesis of 5-phenylpyrrolo[1,2-b][1,2,5]-triazepin-2(3H)-ones

The synthesis of a series of 5-phenylpyrrolo[1,2-b][1,2,5]triazepin-2(3H)-ones 1 as potential anxiolytic agents is described. Benzoylation of 1-phthalimidopyrrole, followed by hydrolysis, gave the 1-amino-2-benzoylpyrroles 3 . These were further functionalized to give the penultimate 1-aminoacetamido-2-benzoylpyrroles 8 and 9 , which were cyclized to the target pyrrolotriazepines 1.     

Synthesis of indeno[2,1-b][1,4]benzothiazine derivatives from 2-bromoinden-1-ones

2-Bromoinden-1-ones 2 were condensed with 6-substituted 3-aminopyridine-2(1H)-thiones to produce a new type of 4-azaindeno[2,1-b][1,4]benzothiazine derivatives 3 . Substituted 6-phenylindeno[2,1-b][1,4]benzothiazines 4 were also prepared by reacting 2-bromo-5-methoxy- and 2,6-dibromo-5-methoxyinden-1-ones with o-aminobenzenethiol.     

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.     

Facile Synthesis of 2-Alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones

Isothiocyanate 2, obtained from aza-Wittig reaction of iminophosphorane 1 with CS₂, reacted with amine to give 2-thioxo-2,3,5,6,7,8-hexahydrobenzothieno[2,3-d]pyrimidin-4(1H)-ones 4 in the presence of sodium ethoxide. S-Alkylation of 4 produced 2-alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones 5 in good yields.     

Reduction of 6/7-substituted 3-phenyltrop-3-en-2-ones: stereoselectivity and conformational analysis of the products

Reduction of 6/7-carboethoxy-3-phenyltrop-3-en-2-ones with H₂/Pd/C and NaBH₄ was studied in order to find a stereoselective route to the corresponding 3-phenyltropan-2-ones and 2α/2β-hydroxy-3-phenyltropanes. The 6/7-exo-carboethoxy-3-phenyltrop-3-en-2-ones were selectively reduced by Pd/C to 3β-phenyltropan-2-ones and 2α-hydroxy-3β-phenyltropanes. The corresponding 2β-hydroxy-3β-phenyl analogues were synthesized using NaBH₄, with a yield of 40%. Reduction of 6-endo-carboethoxy-3-phenyltrop-3-en-2-one yielded several products. The corresponding 7-endo-substituted analogue was selectively reduced with both Pd/C and NaBH₄ to 7-endo-carboethoxy-3β-phenyltropin-2-one. Analysis of stereochemically important ¹H NMR spectroscopy parameters was performed for all the products and used for conformational analysis in solution. X-ray analysis was performed for selected compounds.     

Methyl and Phenylmethyl 2-Acetyl-3-{[2-(dimethylamino)-1-(methoxycarbonyl)ethenyl]amino}prop-2-enoate in the Synthesis of heterocyclic systems: Preparation of 3-amino-4H-pyrido-[1,2-a]pyrimidin-4-ones

Methyl 2-acetyl-3-{[2-(dimethylamino)-1-(methoxycarbonyl)ethenyl]amino}prop-2-enoate ( 4 ) and phenyl-methyl 2-acetyl-3-{[2-(dimethylamino)-1(methoxycarbonyl)ethenyl]amino}prop-2-enoate ( 5 ) were prepared in three steps from the corresponding acetoacetic esters, and used as reagents for the preparation of N³-protected 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 10 – 12 , 5H-thiazolo[3,2-a]pyrimidin-5-one 13 , 4H-pyrido[1,2-a]-pyridin-4-one 19 and 2H-1-benzopyran-2-ones 20 – 23 . Free 3-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 24 – 26 were prepared from 10 – 12 by removal of the 2-(methoxycarbonyl)-3-oxobut-1-enyl or 3-oxo-2-[(phenyl-methoxy)carbonyl]but-1-envl as N-protecting group by various methods.