Regioselective dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones mediated by ceric ammonium nitrate

Ceric ammonium nitrate (CAN) has been explored for the regioselective oxidation of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs). Interestingly, we obtained ethyl 2,4-dioxo-6-phenyl-tetrahydropyrimidin-5-carboxylates as the major products during the oxidation of DHPMs by CAN/AcOH at 80 °C. The reaction afforded a mixture of products while employing CAN in organic solvents without additives. However, the regioselective dehydrogenated product, ethyl 6-methyl-4-aryl(alkyl)-pyrimidin-2(1H)-one-5-carboxylate was obtained by performing the reaction with NaHCO₃. The single crystal X-ray crystallography of ethyl 6-methyl-4-(2-phenyl)-pyrimidin-2(1H)-one-5-carboxylate revealed that the oxidized product existed in amidic form rather than aromatized enol form of pyrimidines. The efficiency of the present protocol enabled the synthesis of structurally diverse pyrimidines in moderate to good yields under milder reaction conditions.     

Potassium peroxydisulfate as an efficient oxidizing agent for conversion of ethyl 3,4-dihydropyrimidin-2(1H)-one-5-carboxylates to their corresponding ethyl pyrimidin-2(1H)-one-5-carboxylates

Various ethyl 3,4-dihydropyrimidin-2(1H)-one-5-carboxylates were oxidized to their corresponding ethyl pyrimidin-2(1H)- one-5-carboxylates by potassium peroxydisulfate in refluxing aqueous acetonitrile. The products were obtained in good to excellent yields. The effect of the nature of 4-substituent and also the nature of solvent play an important role on the rate of oxidation.     

Synthesis of 2-Aryl-4-(R-sulfanylmethyl)-3-methyl-6,7-dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyridazin-7-ones

Bromination of ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates gave ethyl 1-aryl-4-(bromoacetyl)-5-methyl-1H-pyrazol-3-carboxylates which were used to alkylate benzenethiol and heterocyclic thiones at the sulfur atom. Reactions of the resulting S-alkylation products with hydrazine or methylhydrazine involved closure of pyridazine ring to afford 2-aryl-3-methyl-4-[phenyl(or hetaryl)sulfanylmethyl]-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-7-ones.     

Synthesis and properties of ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-3-carboxylates

Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates reacted with phenylhydrazine to give the corresponding hydrazones, ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1H-pyrazole-3-carboxylates, which were converted to ethyl 1′-aryl-4-formyl-5′-methyl-1-phenyl-1H,1′H-3,4′-bipyrazole-3′-carboxylates by treatment with the Vilsmeier–Haack reagent. No indole derivatives were formed from the same hydrazones under the Fischer reaction conditions, but cyclization to 2-aryl-3,4-dimethyl-6-phenyl-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-ones was observed.     

Reaction of aromatic aldehydes with β-dicarbonyl compounds in a catalytic system: Piperidinium acetate-1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid

Condensation of aromatic (heteroaromatic) aldehydes with 1,3-dicarbonyl compounds under the 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF₄]) ionic liquid-piperidinium acetate catalytic system (0.2 equiv. of each component) in the absence of a solvent affords, depending on the structures of the reagents, 2-arylidene derivatives of methyl acetoacetate and acetylacetone, diethyl 2,4-bis(trifluoroacetyl)-3-phenylpentanedioate, or dimethyl 2-aryl-4-hydroxy-6-oxocyclohexane-1,3-dicarboxylates. The reactions of the resulting 2-arylidene derivatives with O-methylisourea in the [Bmim][BF₄] ionic liquid produced methyl 2-methoxy-4-methyl-6-aryldihydropyrimidine-5-carboxylates and 1-(2-methoxy-4-methyl-6-phenyldihydropyrimidin-5-yl)ethanone (mixtures of 3,6- and 1,6-dihydro isomers), which were transformed into the corresponding 3,4-dihydropyrimidin-2(1H)-one derivatives. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1199–1204, May, 2005.     

Synthesis of (<Emphasis Type="Italic">S</Emphasis>)-(-)-1,4-diaryl-6-methyl-4-trifluoromethyl-3,4-dihydropyrimidine-2(1<Emphasis Type="Italic">H</Emphasis>)-thiones

(S)-(+)-4-Amino-4-aryl-5,5,5-trifluoropentan-2-one reacted with aryl isothiocyanates containing electron-withdrawing substituents to give (S)-(−)-1,4-diaryl-6-methyl-4-trifluoromethyl-3,4-dihydropyrimidine-2(1H)-thiones.     

Molecular design of pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyridazines

Reactions of arenediazonium chlorides with ethyl 2-methyl-and 2-chloro-4-oxobutanoates gave, respectively, ethyl 2-(arylhydrazono)propanoates and chloro(arylhydrazono)acetates. Ethyl 2-(arylhydrazono)-propanoates reacted with the Vilsmeier-Haak reagent to give ethyl 1-aryl-4-formyl-1 H-pyrazole-3-carboxylates. Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates were obtained by reaction of chloro(arylhydrazono) acetates with acetylacetone. Reactions of the obtained pyrazole derivatives with hydrazine and methylhydrazine led to the formation of the corresponding 3,4-R ₂ ¹ -6-R²-2-aryl-2,6-dihydro-7H-pyrazolo-[3,4-d]pyridazin-7-ones (R¹, R² = H, Me) which were subjected to alkylation and sulfurization.     

Synthesis of 2-(Pyrazol-1-yl)pyrimidine Derivatives by Cyclocondensation of Ethyl Acetoacetate (6-Methyl-4-oxo-3,4-dihydropyrimidin-2-yl)hydrazone with Aromatic Aldehydes

2-(4-Arylidene-3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-6-methylpyrimidin-4(3H)-ones were obtained by reaction of ethyl acetoacetate (6-methyl-4-oxo-3,4-dihydropyrimidin-2-yl)hydrazone with aromatic aldehydes. Successful cyclization occurs with aldehydes containing an auxochromic substituent in the para position.     

An efficient synthesis of 4H,5H-pyrano[3,4-c]pyran-4,5-diones from a suitably functionalized 2H-pyran-2-one

An efficient synthesis of ethyl 7-aryl-2-methyl-4H,5H-pyrano[3,4-c]pyran-4,5-dione-1-carboxylate 5, and ethyl 6-aryl-3-cyano-2H-pyran-2-one-4-acetate 6 has been delineated by reaction of suitably functionalized 2H-pyran-2-ones 1 with ethyl acetoacetate 2.     

Synthesis of phenylpyrrolylpyrroles. Part III

Several ethyl 3-[(3-aryl-4-methyl)-2(1H)-pyrrolyl]-4-methyl-1H-pyrrole-2-carboxylates have been synthesized using two successive ethyl isocyanide addition-cyclizations to the appropriate nitropropene derivatives.     

Catalytic Potential of Pyrazolone Based Dioxidomolybdenum(VI) Complexes for Multicomponent Biginelli Reactions,Epoxidation of Olefins and Oxidative Bromination of Phenol Derivatives

Three different types of dioxidomolybdenum(VI) complexes of 4-acetyl-3-methyl-1-phenyl-5-pyrazolone (Hmp, I )), 3-methyl-1-phenyl-4-propionyl-5-pyrazolone (Hpp, II ), 4-butyryl-3-methyl-1-phenyl-5-pyrazolone (Hbutp, III ), and 4-isobutyryl-3-methyl-1-phenyl-5-pyrazolone (isobutp, IV ) have been isolated and characterized by various spectroscopic (FT-IR, UV/Vis, ¹H and ¹³C NMR) techniques, thermal analysis and single crystal X-ray analysis. These complexes adopt a distorted six-coordinate octahedral geometry where ligands act as bidentate, coordinating through the two O atoms. These complexes have been used as catalysts to explore a single pot multicomponent (benzaldehyde or its derivatives, urea/thiourea and ethyl acetoacetate/phenyl acetoacatate) Biginelli reaction producing biologically active 3,4-dihydropyrimidin-2-(1H)-one and 3,4-dihydropyrimidin-2-(1H)-thione based biomolecules under solvent-free conditions. Presence of H₂O₂ improves the yield of dihydropyrimidin-2-(1H)-one but it acts as poison for the later molecule. Epoxidation of internal and terminal alkenes mainly resulted in the formation of the corresponding epoxide. The catalytic oxidative bromination of thymol, a reaction facilitated by vanadium dependent haloperoxidases, resulted in the formation of three product namely 2-bromothymol, 4-bromothymol and 2,4-bromothymol. Other phenol derivatives have also been brominated effectively.     

Bromination-Dehydrobromination of 4-Aryl-5-nitro-6-phenyl-3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

Depending on the conditions, bromination of 4-aryl-5-nitro-6-phenyl-3,4-dihydropyrimidine-2(1H)-ones and subsequent dehydrobromination gives either 4-aryl-5-nitro-6-phenylpyrimidin-2(1H)-ones or their mixtures with the corresponding 4-aryl-5-bromo-6-methoxy-5-nitro-6-phenyltetrahydropyrimidin-2-ones which are formed as two diastereoisomers.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 3, 2005, pp. 425–430.Original Russian Text Copyright © 2005 by Sedova, Gatilov, Shkurko.     

Direct heterocyclization of tetrahydroisoquinolin-1-ylideneacetic acids by the action of 5-arylfuran-2,3-diones

Aroylketenes generated in situ by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (1Z,3Z)-4-aryl-4-hydroxy-1-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)-ylidene]but-3-en-4-ones. The crystalline and molecular structure of (1Z,3Z)-4-hydroxy-1-[6,7-dimethoxy-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-4-phenylbut-3-en-2-one was studied by X-ray diffraction.     

Über die Einwirkung von Ammoniak auf 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon

Zusammenfassung 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon (6 b) reagiert mit flüss. NH₃ zu 6-Chlor-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (7), mit NH₃ in absol. Alkohol zu 6-Chlor-4-hydroxy-3-jod-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (9). Der Mechanismus dieser Reaktionen wird diskutiert.

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The reaction of ammonia with 5-Chloro-2-(N-methyl-iodo-methanesulfonamido)-benzophenone

The reaction of 5-chloro-2-(N-methyl-jodomethanesulfon-amido)-benzophenone (6b) with liquid or absol. alcoholic ammonia leads to 6-chloro-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (7) and 6-chloro-4-hydroxy-3-jodo-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (9) resp. The mechanism of these reactions is discussed.

     

1,6- and 1,7-naphthyridines. II. Synthesis from acyclic precursors

A number of 8-hydroxy-6-methyl-1,6-naphthyridin-5(6H)-one-7-carboxylic acid alkyl esters 3 and the isomeric 5-hydroxy-7-methyl-1,7-naphthyridin-8(7H)-one-6-carboxylic acid alkyl esters 4 were synthesized from acyclic precursors obtained starting from quinolinic anhydride 5. Thus, methanolysis of 5 afforded the hemiester 6 which treated with oxalyl chloride and sarcosine ethyl ester gave 3-(N-ethoxycarbonylmethyl-N-methylcarbamoyl)pyridine-2-carboxylic acid methyl ester 8. Compound 8 was cyclized to naphthyridines 3a-e with sodium alkoxides. The isomeric naphthyridines 4a-c were obtained by cyclization of the open intermediary 2-(N-ethoxycarbonylmethyl-N-methylcarbamoyl)pyridine-3-carboxylic acid methyl ester 9 obtained by a route that involves treatment of 5 with sarcosine ethyl ester and esterification with diazomethane. Spectroscopic properties (¹H nmr, uv, ir) of compounds 3 and 4 are discussed and confirmed the proposed structures.     

Five-membered 2,3-dioxo heterocycles: LV. Reaction of methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with ethyl 3-arylaminobut-2-enoates

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with ethyl 3-aryl-aminobut-2-enoates to give the corresponding ethyl 1,7-diaryl-4-aroyl-3-hydroxy-8-methyl-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-9-carboxylates.     

Reaction of (S)-(+)-4-amino-4-aryl-5,5,5-trifluoropentan-2-ones with α-chlorobenzyl isocyanates. Synthesis of (S)-(+)-4-aryl-6-(2-arylethenyl)-4-trifluoromethyl-3,4-dihydro-pyrimidin-2(1H)-ones

(S)-(+)-4-Amino-4-aryl-5,5,5-trifluoropentan-2-ones reacted with 6h-chlorobenzyl isocyanates with formation of (S)-(+)-4-aryl-6-(2-arylethenyl)-4-trifluoromethyl-3,4-dihydropyrimidin-2(1H)-ones.     

N-ethoxycarbonylamidines as starting materials and intermediates in the synthesis of heterocyclic compounds

Treatment of N-ethoxycarbonylthioamides ( 1 ) with primary aromatic amines yields N-aryl-N′-ethoxy-carbonylamidines ( 2 ), which thermally cyclize to 2-aryl-4(3H)-quinazolinones ( 6 ). Analogous reactions of 1 with ethyl 3-aminocrotonate and with 2-amino-2-thiazoline lead respectively to ethyl 2-aryl-3,4-dihydro-6-methyl-4-oxo-5-pyrimidinecarboxylates ( 10 ) and to 2-aryl-6,7-dihydro-4H-thiazolo[3,2-a]-1,3,5-triazin-4-ones ( 14 ), presumably through the corresponding N-ethoxycarbonylamidines.     

An unusual oxidation-dealkylation of 3,4-dihydropyrimidin-2(1H)-ones mediated by Co(NO3)2·6H2O/K2S2O8 in aqueous acetonitrile

4-Aryl-6-methyl-3,4-dihydropyrimidin-2(1H)-one (DHPM) scaffolds of Biginelli type were oxidized using Co(II)/S₂O₈²⁻ and the reaction afforded 6-unsubstituted pyrimidin-2(1H)-ones through an unprecedented dealkylation process. 4-Alkyl DHPMs under similar conditions afforded yet another unusual product, ethyl tetrahydropyrimidin-2,4(1H,3H)-dione-5-carboxylate.     

Microwave assisted synthesis of some new thiazolopyrimidine, thiazolodipyrimidine and thiazolopyrimidothiazolopyrimidine derivatives with potential antioxidant and antimicrobial activity

Biginelli reaction of ethyl acetoacetate, thiourea and the appropriate aromatic aldehyde was used to produce ethyl 4-aryl-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylates, that reacted with bromomalononitrile to give ethyl 3-amino-5-aryl-2-cyano-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylates rather than the isomeric 7H-thiazolo[3,2-a]pyrimidines. Thiazolopyrimidine derivatives reacted with carbon disulphide to yield ethyl 9-aryl-7-methyl-2,4-dithioxo-2,3,4,9-tetrahydro-1H-thiazolo[3,2-a:4,5-d']dipyrimidine-8-carboxylates, that reacted with phenacyl bromide to produce ethyl 8-methyl-10-(4-methoxyphenyl)-3-substituted-5-thioxo-2(un)subatituted-10H-thiazolo[3',2':1',2']pyrimido[4',5':4,5]thiazolo[3,2-a]pyrimidine-9-carboxylates. The aforementioned reactions were carried out using both conventional chemical methods and with the assistance of microwave irradaition. Comparison between both methods showed that the microwave assisted method is preferable because of the time reduction and yield improvements achieved. The new compounds were tested for their biological activity as antioxidants, antibacterial or antifungal agents. Some of the new compounds were found to have moderate to good antioxidant and antimicrobial activities.