Reaction of polychloroacetaldehyde arylsulfonylimines with 2-amino-6<Emphasis Type="Italic">H</Emphasis>-1,3-thiazine-6-thiones and 2-amino-4-phenyl-6<Emphasis Type="Italic">H</Emphasis>-1,3-thiazin-6-one

2-Amino-4-R-6H-1,3-thiazine-6-thiones and 2-amino-4-phenyl-6H-1,3-thiazin-6-one react with highly electrophilic N-arylsulfonylimines of chloral and phenyldichloroacetic aldehyde at the exocyclic amino group affording in good yields products of nucleophilic addition to the azomethine group of imines: N-[2-polychloro-1-(6-thioxo-4-R-6H-1,3-thiazin-2-ylamino)ethyl]- or -[2-polychloro-1-(6-oxo-4-phenyl-6H-1,3-thiazin-2-ylamino)ethyl]arenesulfonamides.     

Efficient syntheses of novel indeno[1,2-b]chromenone derivatives via hetero-Diels-Alder reactions of 2-(arylmethylene)-1H-indene-1,3(2H)-diones with enaminones

Efficient syntheses of novel 10-aryl-5a-(arylamino)-9-hydroxy-5a,6,7,8-tetrahydroindeno[1,2-b]chromen-11(10H)-one derivatives has been reported by [4+2] cycloaddition reactions of electron-deficient 2-(arylmethylene)-1H-indene-1,3(2H)-dione heterodienes with electron-rich enaminones in [bmim]BF₄ at 80?°C and in acetic acid at 80?°C. Dimedone/cyclohexane-1,3-dione enaminones have been used as dienophiles in Inverse Electron Demand hetero-Diels-Alder reactions. The products were obtained in high yields by a simple work up.     

Preparation of 2-Alkyl- and 2-Acylpropenals from 5-(Trifluoromethanesulfonyloxy)-4H-1,3-dioxin: A Versatile Acrolein α-Cation Synthon

5-(Trifluoromethanesulfonyloxy)-4H-1,3-dioxin (3) participates in a variety of nucleophilic substitution reactions with cuprate reagents or in palladium catalyzed cross-coupling reactions to provide 5-substituted-4H-1,3-dioxins 5. Upon thermolysis, these compounds undergo facile retrocycloaddition reactions to generate the corresponding 2-substituted acroleins which, if necessary, can be trapped in situ with dienes or heterodienophiles. In particular, the heretofore unknown 2-acylacroleins can be generated using this methodology and trapped with enol ethers to afford 5-acyl-3,4-dihydro-2H-pyrans (6g,h), a substructural unit common to many natural products.     

Preparative synthesis of 2,2-dimethyl-5-(trifluoroacetyl)-1,3-dioxane-4,6-dione (2-trifluoroacetyl Meldrum's acid) and 2,2-dimethyl-6-(trifluoromethyl)-4H-1,3-dioxin-4-one and their synthetic usefulness as (trifluoroacetyl)ketene precursors

A simple and reliable method for the preparation of 2,2-dimethyl-5-(trifluoroacetyl)-1,3-dioxane-4,6-dione and 2,2-dimethyl-6-(trifluoromethyl)-4H-1,3-dioxin-4-one on a multigram scale was developed. These (trifluoroacetyl)ketene precursors were used in the hetero-Diels-Alder reaction with dialkylcyanamides and 1-ethoxyprop-1-yne, as well as in some reactions with nucleophiles.     

Condensation of 5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with haloacetic acids

Reactions of triazolethiones with haloacetic acids were studied with 5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione as an example. It was proved for the first time by X-ray diffraction that the cyclocondensation of these compounds proceeds regiospecifically to give 2-(4-methylphenyl)[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-one rather than its isomer 3-(4-methylphenyl)[1,3]thiazolo[2,3-c][1,2,4]triazol-5(6H)-one.     

Synthesis of novel chiral bis(2-oxazolinyl)xanthene (xabox) ligands and their evaluation in catalytic asymmetric 1,3-dipolar cycloaddition reactions of nitrones with 3-crotonoyl-2-oxazolidinone

Chiral 4,5-bis(2-oxazolinyl)-(2,7-di-tert-butyl-9,9-dimethyl)-9H-xanthenes (xabox) were synthesized and the chiral environments were evaluated in catalytic asymmetric 1,3-dipolar cycloaddition reactions of nitrones resulting in good to excellent enantioselectivities. 1,3-Dipolar cycloaddition reactions of nitrones with 3-crotonoyl-2-oxazolidinone in the presence of a bis(2-oxazolinyl)xanthene (4c; xabox-Bn) and Mn(II) or Mg(II) complex as a chiral Lewis acid catalyst proceeded smoothly to give the corresponding cycloadducts ranging from 96:4 to >99:1 of endo:exo ratio and ranging from 91% to 98% ee for the endo adduct.     

New Cycloadditon Reaction of 2-Chloroprop-2-enethioamides with Dialkyl Acetylenedicarboxylates: Synthesis of Dialkyl 2-[4,5-bis(alkoxycarbonyl)-2-(aryl{alkyl}imino)-3(2H)-thienylidene]-1,3-dithiole-4,5-dicarboxylates

The 1,3-dipolar cycloaddition of 1,2-dithiole-3-thiones with alkynes to form 1,3-dithioles is one of the most studied reactions in this class of polysulfur-containing heterocycles. Nucleophilic substitution of chlorine atoms in dimethyl 2-(1,2-dichloro-2-thioxoethylidene)-1,3-dithiole-4,5-dicarboxylate, which was obtained by addition one molecules of DMAD to 4,5-dichloro-3H-1,2-dithiole-3-thione, led to a series of 2-chloro-2-(1,3-dithiol-2-ylidene)ethanethioamides. Cycloaddition reaction of 2-chloro-2-(1,3-dithiol-2-ylidene)ethanethioamides with activated alkynes led to the unexpected formation of 2-(thiophen-3(2H)-ylidene)-1,3-dithioles via new intermediate, 1-(1,3-dithiol-2-ylidene)-N-phenylethan-1-yliumimidothioate. Structure of dimethyl 2-(4,5-bis(methoxycarbonyl)-2-(phenylimino)thiophen-3(2H)-ylidene)-1,3-dithiole-4,5-dicarboxylate was finally proven by single crystal X-ray diffraction study. Optimized reaction conditions and a mechanistic rationale for the 1,3-dipolar cycloaddition of novel intermediate are presented.     

Synthesis of 7-iodo(arylsulfanyl)methyl-7,8-dihydro-[1,3]thiazolo[2,3-i]purinium pentaiodide (perchlorates) and their transformation into 4-amino-5-(1,3-thiazol-2-yl)imidazole derivatives

Intramolecular electrophilic cyclization of 6-allylsulfanylpurine by the action of iodine and arenesulfenyl chlorides gave 7-iodomethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium pentaiodide and 7-arylsulfanylmethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium perchlorates, respectively. 7-Iodomethyl-7,8-dihydro-[1,3]thiazolo[2,3-i]purin-6-ium iodide reacted with sodium and potassium alkoxides to produce alkyl N-[5-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-4-yl]formimidates, and its reaction with secondary cyclic amines afforded 5-(4-methyl-1,3-thiazol-2-yl)-N-[morpholin-4-yl(or piperidin-1-yl)methylidene]-1H-imidazol-4-amines. Successive treatment of 7-arylsulfanylmethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium perchlorates with sodium acetate and morpholine led to the formation of 5-(4-arylsulfanylmethyl-4,5-dihydro-1,3-thiazol-2-yl)-N-(morpholin-4-ylmethylidene)-1H-imidazol-4-amines.     

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).     

Synthesis of 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids

Nitration of 2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one gave its 5-nitro derivative which was subjected to alkylation with dimethyl sulfate, diethyl sulfate, and benzyl(dimethyl)phenylammonium chloride. The resulting 1,3-dimethyl-, 1,3-diethyl-, and 1,3-dibenzyl-5-nitro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones were reduced to the corresponding 1,3-dialkyl-5-amino-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones, and the latter reacted with itaconic acid to produce 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids. 1-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acid was obtained by analogous reaction with 5-amino-2,3-dihydro-1H-imidazo[4,5-b]-pyridin-2-one.     

The unexpected cyclization routes of N,N′-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines in polyphosphoric acid medium

The unexpected results of the cyclization reactions of N,N′-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines [1,3-C₆H₄-(NHCRCHC(O)CF₃)₂], where R = H, Me, and Ph, in a strongly acidic medium (PPA), allowing the synthesis of new trifluoromethylated heterocycles containing the 1,7-phenanthroline nucleus in 32-40% yields and 7-aminoquinolines (38-40% yields), is reported. The bis-enaminoketone intermediates were easily isolated from the reactions of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones with 1,3-phenylenediamine in ethanol under mild conditions (68-86% yields).     

Electrophilic cyclization of <Emphasis Type="Italic">N</Emphasis>-allyl(propargyl)-5-amino-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-4-carboxamides. Synthesis of 4-[(dihydro)oxazol-2-yl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-5-amines

N-Allyl-5-amino-1H-pyrazole-4-carboxamides in reactions with polyphosphoric acid, with N-halosuccinimides in chloroform, and with (chlorosulfanyl)benzenes in nitromethane in the presence of lithium perchlorate underwent cyclization involving the N-allylamide fragment to give 4-[5-methyl(halomethyl)-4,5-dihydrooxazol-2-yl]-1H-pyrazol-5-amines and 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methyl]-4,5-dihydro-1,3-oxazolium perchlorates, respectively. Analogous reactions of N-propargyl-5-amino-1H-pyrazole-4-carboxamides with polyphosphoric acid afforded 4-(5-methyloxazol-2-yl)-1H-pyrazol-5-amines, and with (chlorosulfanyl) benzenes, 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methylidene]-4,5-dihydro-1,3-oxazolium perchlorates.     

A new domino-Knoevenagel-hetero-Diels-Alder reaction

Various novel 3,5a,6,11b-tetrahydro-2H,5H-chromeno[4′,3′:4,5]thiopyrano[2,3-d][1,3]thiazol-2-ones were synthesized in 60-80% yields via domino-Knoevenagel-hetero-Diels-Alder reactions of 4-thioxo-1,3-thiazolidin-2-one with 3,7-dimethyl-6-octenal, 2-allyloxybenzaldehydes and 2-formylphenyl (E)-3-aryl-2-propenoates with base catalysis. The possibility of stereo- and regioselective cycloaddition was investigated.     

Synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones

An efficient method for the synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones from various 2-dimethylaminomethylidenecyclohexane-1,3-diones, (1,3-thiazol-2-yl)acetonitriles, and dimethylformamide dimethyl acetal was developed. These transformations proceeded through intermediate 2-[2-(4-aryl-1,3-thiazol-2-yl)-2-cyanoethenyl]-3-oxocyclohex-1-en-1-olates. They were isolated as piperidinium salts and used in further heterocyclization reactions with aromatic amines, giving novel 1-aryl-3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones. These compounds were also obtained by preparative three-step “one pot” synthesis under controlled microwave irradiation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 412–417, February, 2008.     

Effect of solvent on the regioselective synthesis of spiropyrazoles

1,3-Dipolarcycloaddition reactions of 6-arylmethylene-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones (1) with nitrilimines 3 were investigated in benzene and chloroform. The reaction products were 2′,4′,6,7,8,9-hexahydro-2′,4′,5′-triaryl spiro[benzocycloheptene-6(5H),3′(3H-pyrazol)-5-ones (4) or 2′,3′,6,7,8,9-hexahydro-2′,3′,5′-triaryl spiro[benzocycloheptene-6(5H),4′(4H-pyrazol)-5-ones (5). X-ray crystallographic analysis was carried out for compound 5b. It was found that the regioselectivity of the produced compounds was altered based on changing solvent type.     

Isopropylidenemalononitrile in the synthesis of 2-amino-4,6,6-trimethylcyclohexa-2,4-diene-1,1,3-tricarbonitrile, 6-amino-2-(4-methoxybenzoylmethylsulfanyl)-4,4-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrile, and fused 2-aminopyrans according to Michael

Michael reactions of isopropylidenemalononitrile with cyanothioacetamide (in the presence of 4-methoxyphenacyl bromide), cyclohexane-1,3-dione, and 4-hydroxycoumarin, gave 6-amino-2-(4-methoxy-benzoylmethylsulfanyl)-4,4-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrile, 2-amino-4,4-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile, and 2-amino-4,4-dimethyl-5-oxo-4H,5H-pyrano[3,2-c]-chromene-3-carbonitrile, respectively. In the reaction of isopropylidenemalononitrile with cyanoacetamide, only dimerization product of the former, 2-amino-4,6,6-trimethylcyclohexa-2,4-diene-1,1,3-tricarbonitrile, was isolated. Its structure was proved by X-ray analysis.     

Five-membered 2,3-dioxo heterocycles: CVI. Acylation of substituted (Z)-2-[1,3,4,4a,5,10b-Hexahydrophenanthridin-6(2H)-ylidene]acetamide with aroylketenes. crystal and molecular structure of substituted N-{(Z)-2-[1,3,4,4a,5,10b-Hexahydrophenanthridin-6(2H)-ylidene]acetyl}acrylamide

Aroylketenes generated by thermolysis of 6-aryl-2,2-dimethyl-4H-1,3-dioxin-4-ones reacted with (Z)-2-[4a,7,10-trimethyl-1,3,4,4a,5,10b-hexahydrophenanthridin-6(2H)-ylidene]acetamide to give (Z)-3-aryl-3-hydroxy-N-{(Z)-2-[4a,7,10-trimethyl-1,3,4,4a,5,10b-hexahydrophenanthridin-6(2H)-ylidene]acetyl}acrylamides whose structure was confirmed by X-ray analysis.     

Synthesis, structure, and photoisomerization of derivatives of 2-(2-quinolyl)-1,3-tropolones prepared by the condensation of 2-methylquinolines with 3,4,5,6-tetrachloro-1,2-benzoquinone

A series of novel derivatives of the 1,3-tropolone (β-tropolone) system—2-(2-quinolyl)-5,6,7-trichloro-1,3-tropolones and 2-(2-quinolyl)-4,5,6,7-tetrachloro-1,3-tropolones have been prepared by the acid-catalyzed reaction of 2-methylquinolines with 3,4,5,6-tetrachloro-1,2-benzoquinone. The molecular structures of two compounds, 2-(4-chloro-6,8-dimethyl-5-nitro-2-quinolyl)-5,6,7-trichloro-1,3-tropolone 8 and 2-(4-chloro-7,8-dimethyl-5-nitro-2-quinolyl)-4,5,6,7-tetrachloro-1,3-tropolone 9, have been determined using X-ray crystallography. According to the performed DFT B3LYP/6-311++G^∗∗ calculations the tautomeric (OH) and (NH) forms of β-tropolones 8 and 9 are nearly energy equivalent, the latter being more stabilized in polar media. Photolysis of 2-(2-quinolyl)-1,3-tropolones in heptane solution leads to the disrotatory electrocyclic rearrangement resulting in the formation of a mixture of E- and Z-isomers of 3-[2(1H)-quinolinylyden]-bicyclo[3.2.0]hept-6-en-2,4-dione derivatives.     

Cyclisation of 4-[2-Cyclofentenyl]-3-Hydroxy [1] Benzopypan-2-One

4-[2-cyclopentenyl]-3-hydroxy [1] bonzopyran-2-one(3) was cyclised to the bicyclie coumar in-1,3-ethano-2-bromo-1,2-dihydro-3H-pyrano [2,3-c] [1] benzopyran-5-one (6) by a sequence of reactions viz. acetylation of 3, addition of bromine to cyclopenteny double bond and treating the resulting acetyldibromo compound (5) with 4% alcoholic KOH, Cyclisation of compound (3) with mercuric acetate in methanol gave condensed furan derivative 7 which on reductive demercuration with zinc borohydride in dimethoxyethane gave the 1,3-propano-1,2-dihydrofuro [2,3-c] [1] benzopyran-4-one, 8. Cyclisation of compound 2 with come. H₂SO₄ furnished a mixture of bicyclic derivative 9 ad furo coumarin derivative 8.     

Synthesis of annelated [a]aza-anthracenones and thieno[3,2-g]aza-naphthalenones through ring transformation of 2H-pyran-2-one followed by photocyclization

A concise synthesis of some new classes of heterocycles (4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a-diaza-cyclopenta[a]anthracen-6-carbonitriles and 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a-diazabenzo[a]anthracene-7-carbonitriles) has been developed by the ring transformation of suitably functionalized 2H-pyran-2-one with α-oxoketene cyclic aminals to intermediates (8-aroyl-5-aryl-2,3-dihydro-1H-imidazo[1,2-a]pyridine-7-ylidene)-acetonitriles and (9-aroyl-6-aryl-1,2,3,4-tetrahydropyrido[1,2-a]pyrimidin-8-ylidene)-acetonitriles) followed by their photocyclization either in CHCl₃ or acetonitrile. This reaction was further explored for the synthesis of methyl 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carboxylate, 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carbonitriles, 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a,10-triazabenzo[a]anthracene-7-carbonitriles, 4-aryl-10-oxo-1,2,3,10-tetrahydro-9-thia-1,3a-diazadicyclopenta[a,g]naphthalene-6-carbonitriles and 5-aryl-11-oxo-1,3,4,11-tetrahydro-2H-10-thia-1,4a-diazacyclopenta[b]phenanthrene-7-carbonitriles from the similar reactions.