Reactions of 1,3-Dialkyl-5-amino-1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-ones with acetylacetone and ethyl acetoacetate

1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones reacted with acetylacetone to give the corresponding 4-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)pent-3-en-2-ones which underwent intramolecular cyclization to 1,3-dialkyl-5,7-dimethyl-1,3-dihydro-2H-imidazo[4,5-b]-[1,8]naphthyridin-2-ones on heating in polyphosphoric acid or diphenyl ether. Analogous reaction of 1,3-dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones with ethyl acetoacetate led to the formation of ethyl 3-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)but-2-enoates whose cyclization afforded 1,3-dialkyl-8-hydroxy-7-methyl-1,3-dihydro-2H-imidazo[5,4-b][1,8]naphthyridin-2-ones.     

Heterocyclic compounds from 2-(alkoxycarbonylcyanomethylene)-1,3-dioxolanes

2-(Alkoxycarbonylcyanomethylene)-1,3-dioxolanes reacted with hydrazines and hydroxylamine to yield 1-substituted 4-alkoxycarbonyl-5-amino-3-(2′-hydroxyethoxy)pyrazoles and 4-alkoxycarbonyl-5-amino-3-(2′-hydroxyethoxy)isoxazoles respectively. With guanidine and benzamidine 2-substituted (R = NH₂, C₆H₅) 5-cyano-6-(2′-hydroxyethoxy)pyrimidin-4-ones were obtained. Reaction of 2-(cyanomethoxycarbonylmethylene)-1,3-dioxolane with 1,3-diaminopropane afforded 2-(cyanomethoxycarbonylmethylene)-1,3-hexahydro-pyrimidine whereas treatment of the same compound with 4,5-dimethyl-1,2-phenylenediamine gave 2-(cyanomethoxycarbonylmethylene)-5,6-benzimidazoline. The structures of pyrazoles and pyrimidones were assigned on the basis of ¹H-{¹H} and ¹³C-{¹H}-nOe experiments.     

Synthesis of Some 3-Substituted 1,2-Dihydroindoles

The reaction of 4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6-methyl carboxylate 2 with hydrazine hydrate in methanol gave 4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6-carbonylhydrazine 3. Furthermore, the reaction of 3 with carbon disulfide and then hydrazine hydrate afforded 3-[6-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4-oxo-1,3-thiazin-2-yl] hydrazone-1,3-dihydroindol-2-one 5. the latest reacted with DMAD to give {6-hydroxy-3-[4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6yl]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-ylidene}methoxycarbonylmethylene 6.     

Synthesis of putative radioprotectors on the basis of cyclic isotioureas derivatives

The present work deals with the synthesis of sixteen compounds with putative inhibiting activity towards NO-synthase on the basis of 2-amino-2-thiazoline and 2-amino-5,6-dihydro-4H-1,3-thiazine.     

Crystal and Molecular Structures of Phosphonolactone Derivatives of Chromone

The crystal structure of chromone hydrazonium salt (±)-1-hydroxy-1-oxo-3-phenyl-1,3-dihydro-1λ⁵-2,1-oxaphospholo[4,5-b]-4H-1-benzopyran-4-one (2) and its acid (±)-1-hydroxy-1-oxo-3-phenyl-1,3-dihydro-1λ⁵-2,1-oxaphospholo[4,5-b]-4H-1-benzopyran-4-one (3) have been solved. Condensed rings are almost planar, the P atom adopts nearly tetragonal geometry. The molecular packing is influenced by inter- and intramolecular contacts, which can be recognized as hydrogen bonds.     

Dinuclear rhenium(I) carbonyl complexes based on π-conjugated polypyridyl ligands with tetrathiafulvalenes: Syntheses, crystal structures, properties and DFT calculations

A series of tetrathiafulvalene-substituted 2,3-di(2-pyridyl)quinoxaline (dpq) ligands, 2-(4,5-bis(methylthio)-1,3-dithiol-2-ylidene)-6,7-di(pyridin-2-yl)- [1,3]dithiolo[4,5-g]quinoxaline (L₁), dimethyl-2-(6,7-di(pyridin-2-yl)-[1,3]dithiolo[4,5-g]quinoxalin-2-ylidene)-1,3-dithiole-4,5-dicarboxylate (L₂), and 2-(5,6-dihydro-[1,3]dithiolo[4,5-b] [1,4]dithiin-2-ylidene)-6,7-di(pyridin-2-yl)-[1,3]dithiolo[4,5-g]quinoxaline (L₃), have been prepared. Reactions of these ligands with Re(CO)₅Cl afford the corresponding dinuclear rhenium(I) carbonyl complexes, Re₂(L)(CO)₆Cl₂ (L = L₁, 5a; L = L₂, 5b; L = L₃, 5c). All new compounds are fully characterized by ¹H NMR, IR and mass spectroscopies. The crystal structures of 5a and 5b have been studied. Optimized conformations and molecular orbital diagrams of 5a−5c have been calculated with density functional theory (DFT). The spin-allowed singlet−singlet electronic transitions of all complexes have been calculated with time-dependent DFT (TDDFT), and the UV-Vis−NIR spectra are discussed based on the theoretical calculations.     

Tetraaryl-1,3-dioxolane-4,5-dimethanols as catalysts for the addition of trimethylsilyl cyanide to benzaldehyde and the oxirane ring

The synthesis of 1,2-, 1,3-, and 1,4-phenylene-bis[(4R,5R)-4,5-di(hydroxydiphenylmethyl)-1,3-dioxolane]s (ortho-, meta-, and para-bis-(R,R)-TADDOLs) and bis[4-{[(4R, 5R)-4,5-di(hydroxydiphenylmethyl)]-1,3-dioxolan-2-yl}phenyl]methane was carried out. The possibilities of the use of these compounds as catalysts for the C-C bond formation in the addition of Me₃SiCN to benzaldehyde and the oxirane ring opening in cyclohexene oxide by Me₃SiCN were investigated. The catalytic activity of different bis-(R, R)-TADDOLs in this series depends on their structure. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1451–1458, August, 2007.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor^® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.     

Synthesis of 2-(3,3-Dicyano-2-propenylidene)-4,4,5,5-tetramethyldioxolane and Its Reactions with Hydrazine and Primary Amines

Reactions of 2-(-ethoxyvinyl)-4,4,5,5-tetramethyl-4,5-dihydro-1,3-dioxol-1-ium salts with cyanomethylene compounds gave the corresponding 2-(2-propenylidene)-1,3-dioxolane derivatives which reacted with hydrazine and primary amines to afford, respectively, 3-(2-hydroxy-1,1,2-trimethylpropoxy)pyrazole and 1-substituted 6-amino-5-cyanopyridin-2(1H)-ones.     

Synthesis of 2-substituted-5-rnethylthiazolo[ 3,2-b ] -1,2,4-lriazoles and acylatcd 3-amino-2-imino-4-methyl-2-thiazolines

3-Amino-2-imino-4-mcthyl-2-thiazoline, 1, underwent ring closure with ethyl formate, cyanogen bromide and carbon disulfide, giving moderate yields of 2-substituted-5-methylthiazolo[ 3,2-b ]-1,2,4-triazoles, II. Reaction of I-HCl with acid anhydrides (acetic, propionie, trifluoroacetic) resulted in the formation of the corresponding II compounds, whereas other anhydrides (benzoic, perfluoropropionic, perfluorobutyric) gave high yields of 3-aeylamido-2-acylimido-4-melhyl-2-thiazolines. With acid chlorides and I-HCl, in the presence of trielhylamine, mixtures of 2-acyl-irnino-3-aniino-4-methyl-2-thiazolines and 2-aeylimino-3-(diacylamido)-4-methyl-2-thiazolines are formed. Spectral characteristics are reported.     

Synthesis of some sym-triazole derivatives

3,5-Di(hydroxyalkyl) derivatives of 4-amino-1,2,4-triazole and the corresponding derivatives of 1,2,4-triazole obtained by diazotizing them are converted by reaction with SOCl₂ into the hydrochlorides of 4-amino-3,5-di(chloroalkyl)-1,2,4-triazoles and 3,5-di(chloroalkyl)-1, 2,4-triazoles. The dinitrate of 3,5-di(hydroxymethyl)-1,2,4-triazole has been prepared. When the cyanohydrazide of glycolic acid is heated with hydrazine hydrate, 4,5-diamino-3-hydroxymethyl-1, 2,4-triazole is formed.     

Photochemical synthesis of 2-amino-1-hydroxy-9,10-anthraquinone-9-alkyl(aryl)imines

Irradiation of a mixture of 1-aryloxy-2-amino-9,10-anthraquinone and amines in benzene results in formation of the derivatives of 2-amino-1-hydroxy-9,10-anthraquinone-9-alkyl(aryl)imines in a high yield. 2-Amino-1-hydroxy-9,10-anthraquinone-9-aikylimines were shown by¹³C and¹⁵N NMR to exist predominantly in the enaminoquinoid form whereas 2-amino-1-hydroxy-9,10-anthraquinone-9-arylimines exist in the oxyimine form. Sunlight irradiation of the derivatives of 2-benzoylamino-9,10-anthraqumone-9-alkylimines results in formation of the photocyclization products — 4-benzoylaminoanthra-[9,1-d,e]-1,3-oxasinones-7.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 940–944, May, 1993.     

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.     

Synthesis of 2-amino-5,6-dihydro-4H-1,3-thiazines and related compounds by acid catalyzed cyclization of allylic isothiuronium salts

Several allylic isothiuronium salts 6 have been shown to yield 4-substituted 2-amino-5,6-dihydro-4H-1,3-thiazines ( 2 ; R³ = H) and the 2-phenylimino compound 10 on exposure to trifluoroacetic acid or trifluoroacetic acid-stannic chloride. The overall process constitutes a convenient transformation of readily available ketones or aldehydes 3 into the target hetero-cycles. The scope and limitations of this approach are discussed in terms of carbenium ion intermediates ( 7 ). Whereas this method successfully led to the imidazo[2,l-b][1,3]thiazine 13 (93% from 12 ), its application to the synthesis of 2-amino-2-thiazolines (eg. 14 → 15 ) or imidazo-[2,1-b]thiazoles (eg. 16 → 17 ) was unsuccessful. The 2-acetylimino derivatives 9 were found to be useful for purification of the 2-aminothiazines.     

A Convenient Route to New 4,5-Dimercapto-1,3-thiazole Derivatives

A series of 2-X-4-tosyl-5-chloro-1,3-thiazoles (X = OH, OAlk, SH, SAlk, NH₂, NHAlk, NAlk₂, NHAr, etc.) were prepared from accessible 1-tosyl-2,2-dichloroethenyl isothiocyanate. Only some of these compounds containing a moderately labile hydrogen atom peculiarly react with thiophenols in the presence of triethylamine to give 4,5-di(arylthio)-2-(hydroxy- or arylamino)-1,3-thiazoles, which are difficult to prepare by other routes. It is quite possible that, in the course of nucleophilic substitution of the chlorine atom and tosyl residue by the corresponding arylthio groups, a significant role is played by nonaromatic tautomeric forms of functionally 2-substituted 1,3-thiazoles formed by proton transfer to positions 3 and 5 of the heteroring.     

The reaction of 2,2,4,4-tetramethyl-1,3-cyclobutanedione with o-aminophenols,o-aminothiophenol and with aliphatic 2- and 3-hydroxy- and -mercaptoamines

Studies of the reaction of the dione dimer of dimethylketene ( 1 ) with a series of o-aminophenols and with o-aminothiophenol have been carried out. These reactions give 2-[2-(2,4-dimethyl-3-oxopentyl)]benzoxazoles and -benzothiazole, respectively. Aliphatic 2- and 3-hydroxy- and 2- and 3-mercaptoamines yield 2-substituted 2-oxazolines, 5,6-dihydro-4H-1,3-oxazines, 2-thiazolines and 5,6-dihydro-4H-1,3-thiazines.     

Substituted ethyl 2-acyl-3-amino-6-methylthieno[2,3-b]pyridine-4-carboxylates as synthons for novel heterocycles

The triethylamine-catalyzed reaction of 4-substituted ethyl 2-acyl-3-amino-6-methylthieno[2,3-b]pyridine-4-carboxylates IIIa-h with 2,2,6-trimethyl-4H-1,3-dioxin-4-one IV gave 4-substituted ethyl 3-acetyl-2-hydroxy-7-methylthieno[2,3-b:4,5-b′]dipyridine-9-carboxylates Va-h. Some of the thienodipyridines ( V ) reacted with excess IV to give 5-substituted ethyl 3-acetyl-4,8-dimethyl-2-oxo-2H-pyrano[2,3-b]-pyrido[3′,2′:4,5]thieno[2,3-e]pyridine-10-carboxylates VI .     

Five-membered 2,3-dioxo heterocycles: LXXVI. Reaction of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

Methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione to give methyl 11-aryl-12-benzoyl-9-hydroxy-4,6-dimethyl-3,5,10-trioxo-4,6,8,11-tetraazatricyclo[7.2.1.0^2,7]dodec-2(7)-ene-1-carboxylates which underwent thermal recyclization to 1-aryl-3-benzoyl-4-hydroxy-1′,3′-dimethylspiro[pyrrole-2,5′-pyrrolo[2,3-d]pyrimidine]-2′,4′,5,6′(1H,1′H,3′H,7′H)-tetraones.     

Five-membered 2.3-dioxo heterocycles: LXVIII. Three pathways in the reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 3-amino-5,5-dimethylcyclohex-2-en-1-one

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-amino-5,5-dimethylcyclohex-2-en-1-one having no substituent on the nitrogen atom to give 3-aroyl-4-arylamino-6′,6′-dimethyl-6′,7′-dihydro-5H-spiro[furan-2,3′-indole]-2′,4′,5′(1′H,5′H)-triones or methyl 12-aroyl-11-aryl-9-hydroxy-5,5-dimethyl-3,10-dioxo-8,11-diazatricyclo[7.2.1.0^2,7]dodec-2(7)-ene-1-carboxylates. The latter underwent thermal recyclization to 3′-aroyl-1′-aryl-4′-hydroxy-6,6-dimethyl-6,7-dihydrospiro[indole-3,2′-pyrrole]-2,4,5′(1H,1′H,5H)-triones.