A rapid and facile synthesis of new spiropyrimidines from 5-(2-arylethylidene-2-oxo)-1,3-dimethylpyrimidine-2,4,6-triones

A series of new tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraones have been obtained by reaction of 5-(2-arylethylidene-2-oxo)-1,3-dimethylpyrimidine-2,4,6-triones with ureas. A three-component one-pot procedure to the spiranes synthesis was also developed. One-pot reaction of arylglyoxals, 1,3-dimethylbarbituric acid, and dimethylurea led to imidazolyl-1,3-dimethylbarbituric acids. Mechanisms of studied reactions were discussed.     

Regioselective synthesis of pyrano[3,2-c]pyrimidine derivatives via a palladium-catalyzed unusual [1,3] aryloxy shift and cycloisomerization: first report of a [1,3] shift of an aryloxy group

Uracil-annulated pyrano heterocycles are regioselectively synthesized in excellent yields (92-100%) via a palladium-catalyzed unusual [1,3] aryloxy shift followed by 6-endo dig cyclization and [1,3] prototropic shift.     

A NOVEL SYNTHESIS OF SPIRO 1,3-DITHIIN AND SPIRO 1,3-THIAZINE DERIVATIVES UNDER PHASE TRANSFER CATALYSIS (PTC) CONDITIONS

Ketene S,S-acetals 1a, b or ketene N,S-acetals 2a, b reacts in situ with a variety of ylidenemalononitriles to afford the desired spiro [1,3]dithiin heterocycles 3a, b–11a, b or spiro[1,3]thiazine heterocycles 12a, b–20a, b. Treatment of 2-(1-acetyl-2-oxopropylidene)spiro[1,3]thiazine derivatives 13b, 17d, and 18d with malononitrile afforded the corresponding dispiro heterocycles 21, 22, and 23.     

由N-苯基[1,3]苯并噁嗪正离子与烯烃[4+2]反应合成喹啉并[1,2-c][1,3]苯并噁嗪-6-酮衍生物

以BF3·OEt2 为催化剂, 在室温下通过4-羟基-N-苯基[1,3]苯并噁嗪-2-酮的脱羟基产生N-苯基[1,3]苯并噁嗪正离子, 然后与富电子烯烃发生Diels-Alder反应, 合成出了一系列喹啉并[1,2-c][1,3]苯并噁嗪-6-酮和喹啉并[1,2-c][1,3]萘并噁嗪-6-酮衍生物.     

From thiourea to bicyclic structures: an original route to imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines,and 2H,6H-pyrimido[2,1-b][1,3]thiazines

We report an example of an efficient regioselective synthesis of biheterocyclic compounds using thiourea as starting material. In fact, N,N'-bis(dimethylaminomethylene)thiourea (1), easily prepared by double condensation of N,N-dimethylformamide dimethyl acetal with thiourea, can be reacted with haloketones or acrylic dienophiles to give thiazolic (2) and thiazinic (3) diazadienes, respectively, themselves undergoing cyclization reactions to yield imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines without any regioisomeric ambiguity. This straightforward route represents an original and unambiguously regioselective pathway to these valuable heterocycles.     

Facile syntheses of novel benzo-1,3-dioxolo-, benzothiazolo-, pyrido-, and quinolino-fused 5H-benzo[d]-pyrazolo[5,1-b][1,3]-oxazines and 1H-pyrazoles

A number of novel benzo-1,3-dioxolo-, benzothiazolo-, pyrido-, and quinolino-fused 5H-benzo[d]pyrazolo[5,1-b][1,3]-oxazines and 1H-pyrazoles were synthesized utilizing an easy and effective N,N-bond forming heterocyclization reaction. In so doing, the substrate scope of this heterocyclization reaction, which starts with o-nitroheterocyclic aldehydes, was expanded to provide several unique heterocyclic compounds for biological screening. This work further demonstrates the versatility of this simple, base-mediated, one-pot heterocyclization method in the construction of novel heterocycles.     

Heterocycles derived from the condensation of 1,3-propanediamine with phthalic acid derivatives

The condensation of phthalic anhydride with 1,3-propanediamine afforded N-(o-carboxybenzoyl)-1,3-propanediamine (I) which by intravolecular cyclization was transformed into 2,3,4,6-b-tetrahydropyrimido[2,1-a]isoindol-6-one (II) rather than the benzodiazonine (III). An intermediate in the condensation is proposed. The reaction of 1,3-propanediamine with dimethyl phthalate also did not afford III, but rather a more complex product, dibenzo[c,l]-1,6,10,15-tetraazacyclooctadecane-5,11,16,22-tetraone (IX). Reaction of 1,3-propanediamine with phthaloyl chloride gave 6,13-propanodibenz[c,h]-1,6-diazecine-5,7,12,14-tetrone (XII). Spectroscopic data of the heterocycles obtained and chemical properties of II are given.     

Synthesis of Novel Dispiro 1,4-Benzothiazine Hybrid Heterocycles Through 1,3-Dipolar Cycloaddition

The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of acenaphthylene-1,2-dione or isatins and α-amino acids to (E)-methyl/ethyl 2-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-2-ylidene)acetate led to the stereoselective formation of novel dispiro 1,4-benzothiazine hybrid heterocycles in good yields.     

Heteroaromatic annulation studies on 2-[bis(methylthio)methylene]-1,3-indanedione: efficient routes to indenofused heterocycles

2-[Bis(methylthio)methylene]-1,3-indanedione has been shown to be a useful three carbon 1,3-dielectrophilic synthon for the highly efficient regiospecific synthesis of a variety of indenofused five- and six-membered heterocycles via heteroaromatic annulation. The methodology has been further elaborated to the corresponding N,S-acetals leading to amino substituted heterocycles, thus providing further point of diversity in the newly synthesized heterocyclic frameworks. Further, the facile access to cytotoxic indeno[2,1-c]quinolin-7-ones and the novel polycyclic heteroaromatics demonstrates the versatility of heteroaromatic annulation protocol via α-oxoketene-S,S-acetal in generating novel biologically important polycyclic heteroaromatics.     

Synthesis of condensed heterocycles containing a pyrimido[5,4-e][1,3]-thiazine fragment

The cyclocondensation of 4,6-dichloro-2-methylthiopyridine-5-carbaldehyde and heterocyclic thiones such as 1,2,4-triazole-5-thione, imidazolidine-2-thione, imidazole-2-thione, and 4,5-diphenylimidazole-2-thione in dimethylformamide gave tricyclic heterocycles containing a pyrimido[5,4-e][1,3]thiazine fragment. The reaction of 6-chloro-8-methylthio-5H-pyrimido[5,4-e][1,2,4]triazolo[5,1-b][1,3]thiazin-5-ol with diethylamine, pyrrolidine, and morpholine gave the corresponding 6-dialkylaminopyrimidotriazolothiazines.Vilnius University, 2006 Vilnius, Lithuania; e-mail: sigitas.tumkevicius@chf.vu.lt. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 854–856, June, 2000.     

Reaktionen von 4,4-Bis(trifluormethyl)-1,3-diazabuta-1,3-dienen. Synthese trifluormethyl-substituierter Heterocyclenvia Baylis-Hillman-Reaktion

Summary 4,4-Bis(trifluoromethyl)-1,3-diazabuta-1,3-dienes and ,-unsaturated heteromultiple bond systems react to givebis(trifluoromethyl) substituted heterocycles. The first step of the formal [4+2] cycloaddition represents aBaylis-Hillman reaction.

Prof. Dr. Rolf Huisgen zum 75. Geburtstag gewidmet     

Synthesis of [1,3]dithiole and spiro[1,3]dithiole thiopyran derivatives of the [1,2]dithiolo[1,4]thiazine ring system

We report the synthesis of some new polysulfur-nitrogen heterocycles by cycloaddition reactions to readily available tricyclic condensed 1,2-dithiole-3-thiones. Thus, treatment of bis[1,2]dithiolopyrrole ketothione 1 with diacyl acetylenes gave the bis-aducts 2a-d. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine ketothione 3 with 1 equiv of acyl or diacyl acetylenes gave [1,3]dithiolylidenyl[1,2]dithiolo[1,4]thiazines 4a-f in fair to high yields. Catalysis by scandium triflate was used in the reactions that implied the less reactive dipolarophiles. Treatment of 3 with 2 equiv of DBA gave the bis-aduct 5a, and reaction of 4c with DMAD gave the mixed bis-adduct 5b. Cyclic voltammetry of selected examples showed irreversible processes that were influenced by the electrochemical activity of peripheral groups bonded to the heterocyclic system.     

One-step synthesis of some polyfluoroalkylated 1,3-benzodioxoles, 4H-1,3-benzodioxins and dibenzo[d,f] [1,3]dioxepins

Several polyfluoroalkylated heterocyclic compounds containing methylenedioxy group such as 2-(F-alkyl) substituted 1,3-benzodioxole, piperonal, 4H-1,3-benzodioxin, 1,3-dioxolane and 6-(F-alkyl) substituted dibenzo[d, f][1,3]dioxepin have been prepared through double Michael-addition reactions of 2,2-dihydropolyfluoroalkanoates with the corresponding diphenols or diols in high yields.     

亚甲胺叶立德参与的不对称1,3-偶极环加成构建含连续季碳中心的螺四氢吡咯衍生物

Cu(I)催化的亚甲胺叶立德和亚环丙基乙酸乙酯参与的不对称endo-1,3-偶极环加成反应,高效构建了多官能化、含有多个连续季碳中心的5-氮杂-[2,4]庚烷化合物.此反应具有广泛的底物适用性,α-取代的和α-非取代的亚甲胺叶立德和亚环丙基乙酸乙酯都能很好的参与反应,并以很高的产率、优秀的非对映选择性(95:5–98:2 d.r)和对映选择性(87%–98%ee)生成相应的在2,3,4位上含有连续季碳中心的螺四氢吡咯化合物.     

Discovery of 2-aminobuta-1,3-enynes in asymmetric organocascade catalysis: construction of drug-like spirocyclic cyclohexanes having five to six contiguous stereocenters

We present herein for the first time the asymmetric synthesis of drug-like spiranes through reflexive-Michael reaction by using 2-aminobuta-1,3-enyne catalysis under mild conditions.     

[HCo(CO)4]‐Catalyzed Three‐component Cycloaddition of Epoxides,Imines, and Carbon Monoxide: Facile Construction of 1,3‐Oxazinan‐4‐ones

The three‐component [3+2+1] cycloaddition of epoxides, imines, and carbon monoxide to produce 1,3‐oxazinan‐4‐ones has been developed by using [HCo(CO)₄] as the catalyst. The reaction occurs for a wide variety of imines and epoxides, under 60 bar of CO pressure at 50 °C, to produce 1,3‐oxazinan‐4‐ones with different substitution patterns in high yields, and provides an efficient and atom‐economic route to heterocycles from simple and readily available starting materials. A plausible mechanism involves [HCo(CO)₄]‐induced ring‐opening of the epoxide, followed by sequential addition of carbon monoxide and the imine, and then ring closure to form the product accompanied by regeneration of [HCo(CO)₄].     

[HCo(CO)4]‐Catalyzed Three‐component Cycloaddition of Epoxides,Imines, and Carbon Monoxide: Facile Construction of 1,3‐Oxazinan‐4‐ones

The three‐component [3+2+1] cycloaddition of epoxides, imines, and carbon monoxide to produce 1,3‐oxazinan‐4‐ones has been developed by using [HCo(CO)₄] as the catalyst. The reaction occurs for a wide variety of imines and epoxides, under 60 bar of CO pressure at 50 °C, to produce 1,3‐oxazinan‐4‐ones with different substitution patterns in high yields, and provides an efficient and atom‐economic route to heterocycles from simple and readily available starting materials. A plausible mechanism involves [HCo(CO)₄]‐induced ring‐opening of the epoxide, followed by sequential addition of carbon monoxide and the imine, and then ring closure to form the product accompanied by regeneration of [HCo(CO)₄].     

The Divergent Synthesis of Nitrogen Heterocycles by Rhodium(II)‐Catalyzed Cycloadditions of 1‐Sulfonyl 1,2,3‐Triazoles with 1,3‐Dienes

The first rhodium(II)‐catalyzed aza‐[4+3] cycloadditions of 1‐sulfonyl 1,2,3‐triazoles with 1,3‐dienes have been developed, and enable the efficient synthesis of highly functionalized 2,5‐dihydroazepines from readily available precursors. In some cases, the reaction pathway could divert to formal aza‐[3+2] cycloadditions, thus leading to 2,3‐dihydropyrroles. In this context, the titled reaction represents a capable tool for the divergent synthesis of two types of synthetically valuable aza‐heterocycles from common rhodium(II) iminocarbene intermediates.     

Metabolites of felbamate; synthesis of 2-(4-hydroxyphenyl)-1,3-propanediol dicarbamate, 2-phenyl-2-hydroxy-1,3-propanediol dicarbamate,and 2-phenyl-1,3-propanediol monocarbamate

Three major metabolites of felbamate, namely 2-(4-hydroxyphyenyl)-1, 3-propanediol dicarbamate. [4], 2-hydroxy-2-phenyl-1,3-propanediol dicarbamat [12], and 2-phenyl-1,3-propanediol monocarbamate [17] were prepared. The first metabolite, 4, was synthesised from p-methoxy-phenylacetic acid [1] via five steps involving carboxylation, reduction, phosgenation, demethylation, and carbonation. The second one, 12, was prepared from 2-phenyl-1,3-propanediol [7] by the following five steps; phosgenation, halogenation, carbonation, dehalogenation, and ammonolysis. The synthesis of the third metabolite, 17, started with 7, via the following five steps: methylation, phosgenation, carbonation, and demethylation.     

Chemical transformations of 3-aminopyrrolidin-2-ones of the norbornane and cyclopropane series

3-Aminopyrrolidin-2-ones containing a fused norbornane or spirocyclopropane fragment react with benzaldehyde to give azomethines, which can be transformed into N-substituted 3-aminopyrrolidin-2-ones by reduction with sodium borohydride. Diazotization of amino-pyrrolidinones with NaNO₂ in acetic acid results in the elimination of molecular nitrogen and in the formation of acetoxy or unsaturated derivatives (through stabilization of intermediate carbocations). 6-Methylidene4-azaspiro[2.4]heptan-5-one obtained by diazotization of 6-amino-6-methyl-4-azaspiro[2.4]heptan-5-one easily reacts with diazomethane, diazocyclo-propane, and benzonitrile oxide to yield heterocyclic spiranes by means of 1,3-dipolar cycloaddition.