Azines and Their Acyclic Derivatives as Transferers of One-carbon Fragment in Reactions with Pyrazolones

Enehydrazine derivatives have been obtained by the reaction of 6-phenyl-1,2,4-triazine 4-oxide with pyrazolones 2, which on further heating with pyrazolones 2 are converted into the corresponding symmetrical or unsymmetrical derivatives of dipyrazolylmethane. Enehydrazine derivatives of 1,3-dimethyl-5-nitrosouracil and 1,3-dimethylimidazolidine interact with 3-methyl-1-phenyl-5-pyrazolone (2a) with the formation of dipyrazolylmethane derivative. On interacting compound 2a or 3-methyl-1-(p-nitrophenyl)-5-pyrazolone with 3,6-diphenyl-1,2,4-triazine 4-oxide 12 the corresponding 4,4'-bispyrazolones are formed, but the interaction of compound 12 with 3-(p-nitrophenyl)-1-phenyl-5-pyrazolone leads to dipyrazolylmethane derivative. Dipyrazolylmethane derivative is obtained on heating of fervenulin 4-oxide, 2,4-dihydroxy-5-nitropyrimidine, and 1,3,5-triazines: 6-azauracil, 5-azauracil, azacytosine, and 2,4-diamino-s-triazine with pyrazolone 2a.     

Multiple pathways in the synthesis of new annelated analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (emivirine)

Condensation of 3-(3,5-dimethylphenyl)-2-oxocyclopentanecarboxamide (11) with oxalyl chloride and condensation of ethyl 2-benzylamino-5-methyl-3-phenylcyclopent-1-enecarboxylate (17a) with trimethylsilyl isothiocyanate gave 7-(3,5-dimethylphenyl)-6,7-dihydro-5H-cyclopenta[e][1,3]oxazine-2,4-dione (12) and 1-benzyl-5-methyl-7-phenyl-2-thioxo-1,2,3,5,6,7- hexahydrocyclopentapyrimidin-4-one (18a), respectively. Acid catalyzed ring-closure of 6-(4-methyl-1-phenylpent-3-enyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (26) and radical mediated ring-closure of 1,3-bis(benzyloxymethyl)-5-bromo-6-(1-phenylbut-3-enyl)-1H-pyrimidine-2,4- dione (32a) gave 5,5-dimethyl-8-phenyl-5,6,7,8-tetrahydro-1H-quinazoline-2,4- dione (28) and 1,3-bis(benzyloxymethyl)-5-methyl-7-phenyl-1,5,6,7- tetrahydrocyclopentapyrimidine-2,4-dione (33), respectively. Annelated emivirine analogues 7-(3,5-dimethylphenyl)-1- ethoxymethyl-1,5,6,7-tetrahydrocyclopentapyrimidine-2,4-dione (4), 1-ethoxymethyl-5,5-dimethyl-8-phenyl-5,6,7,8-tetrahydro-1H-quinazoline- 2,4-dione (5) and 1-ethoxymethyl-5-methyl-7-phenyl-1,5,6,7- tetrahydrocyclopentapyrimidine-2,4-dione (6) were obtained in few steps from 12, 28 and 18a/33, respectively. These new analogues can be considered as conformationally locaTed analogues of emivirine. However, the compounds 4 6 showed lower activities against HIV-1 than emivirine and it is concluded that the locked conformation disfavours activity against HIV-1.     

Thermal and photochemical rearrangements of 1,4-dithiin sulfoxides

Thermolysis of 2,5-diphenyl-1,4-dithiin-1-oxide afforded 2-formyl-2,4-diphenyl-1,3-dithiole, which was obtained also in photolysis along with another rearranged product, 2-benzoyl-4-phenyl-1,3-dithiole.     

Synthesis and steric structure of 1,3(1,5)-dimethyl-2-phenyl-and -2,4-diphenyl-4-piperidols

1,3(1,5)-dimethyl-2-phenyl- and -2,4-diphenyl-4 piperidols were respectively obtained with the reaction of 1,3-and 1,5-dimethyl-2 phenyl-4-piperidoraes with sodium borohydride and phenyllithium. The steric isomers of the compounds obtained were separated and identified by spectral methods.Moscow State Academy of Precision Chemical Technology, Moscow 117571. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 941–945, July, 1994. Original submitted July 11, 1994.     

Synthesis of 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones as intermediates for the synthesis of C-azanucleosides

The method for the synthesis of 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones is described. It is shown that the reaction of phosphorus trichloride, 2-pyrrolidones and 6-aminopyrimidines brings to condensation producing 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones as intermediates for the synthesis of C-azanucleosides. The reaction of 6-imino-1,3-dimethyl-5-tetrahydro-2-pyrrolylidenhexahydro-2,4-pyrimidinedione with benzoyl chloride produces 10-benzoyl-2,4-dimethyl-6-phenyl-1,2,3,4,8,9-hexahydropyrimido[5,4-e]pyrrolo[1,2-c]pyrimidine-1,3-dione. A method for the selective reduction of the carbomethoxy group of methyl 5-(4-imino-1,3-dimethyl-2,6-dioxohexahydro-5-pyrimidinyliden)-2-pyrrolidine carboxylate by system NaBH₄/1,4dioxane/CoCl₂/PEG-400 is described.     

1,3-Dimethyl-2-phenyl-1,3-diazaphospholidine-2-oxide as ligand for the preparation of luminescent lanthanide complexes

Abstract

Europium(III) coordination compounds having general formula [Eu(β-dike)₃L₂] (β-dike?=?dibenzoylmethanate, tenoyltrifluoroacetonate; L?=?1,3-dimethyl-2-phenyl-1,3-diazaphospholidine-2-oxide) were isolated and characterized. The complexes exhibited bright red emission associated to the ⁵D₀→⁷F_J transitions of the metal center upon excitation with near-UV light, with intrinsic quantum yields around 51% and 65%, respectively, for the dibenzoylmethanate and tenoyltrifluoroacetonate derivatives. More information about the behavior of 1,3-dimethyl-2-phenyl-1,3-diazaphospholidine-2-oxide as an antenna-ligand towards trivalent lanthanide ions was obtained by its coordination to [Ln(NO₃)₃] (Ln?=?Eu, Gd, Tb) metal fragments.     

Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .     

Fluorinated dioxolanes. 3. Nucleophilic reactions of perfluoro-4-methyl-1,3-dioxolanes

Conclusions Perfluoro-2,4-dimethyl-2-fluorocarbonyl-1,3-dioxolane reacts with sodium carbonate to give perfluoro-2-methylene-2-methyl-1,3-dioxolane. Under the reaction conditions, the latter dimerizes to perfluoro-2-(2,4-dimethyl-1,3-dioxolan-2-ylmethylene)-4-methyl-1,3-dioxolane, and on treatment with CsF is converted into perfluoromethyl-(1,3-dioxolany-2-yl)ketone.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 938–942, April, 1989.     

A convenient one-pot synthesis of substituted 2-pyrone derivatives

2-Pyrone derivatives were prepared in a one step procedure from readily available (chlorocarbonyl)phenyl ketene and 1,3-diketones such as 2,4-pentanedione, 1,3-diphenyl-1,3-propanedione, 1-phenyl-1,3-butanedione, 1,3-cyclohexanedione, 5,5-dimethyl-1,3-cyclohexanedione, 1,3-dimethyl-pyrimidine-2,4,6-trione and ethyl 2,4-dioxopentanoate. A mechanism is presented to account for the formation of the products. This method provides an easy route to prepare 3,4,5,6-tetrasubstituted 2-pyrones in good to excellent yields and in a short experimental time.     

Synthesis of Some New Thiazoles and Pyrazolo[1,5-a]pyrimidines Containing an Antipyrine Moiety

Ethyl 2-{2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-(pyrazolin-4-yl)]-2-cyano-1-(phenylamino)vinylthio}-acetate, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]2-(4-oxo-3-phenyl-(1,3-thiazoilidin-2-ylidene))ethanenitrile, 2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]-2-(4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))ethanenitrile, 2-(5-acetyl-4-methyl-3-phenyl(1,3-thiazolin-2-ylidene))-2-[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]ethanenitrile, and ethyl 2-(cyano(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)methylene)-2,3-dihydro-4-methyl-3-phenylthiazole-5-carboxylate were synthesized by treatment of 2-(4-(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)thiazol-2-yl)-3-mercapto-3-(phenylamino)-acrylonitrile with appropriate halo ketones or halo esters. Also, 4-{2-[5,7-dimethyl-2-(phenylamino)(7a-hydropyrazolo[1,5-a]pyrimidin-3-yl](1,-thiazol-4-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one derivatives were synthesized via reaction of 4-{2-[5-amino-3-(phenylamino)pyrazolin-4-yl](1,3-thiazol-2-yl)}-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one with β-diketone or β-keto ester. All synthesized compound were established by elemental analysis, spectral data, and alternative synthesis whenever possible.     

Regioselective 1,3-Dipolar Cycloaddition Reactions of Unsymmetrical Münchnones (1,3-Oxazolium-5-olates) with 2- and 3-Nitroindoles. A New Synthesis of Pyrrolo[3,4-b]indoles

The unsymmetrical mesoionic münchnones 13 (3-benzyl-2-methyl-4-phenyl-1,3-oxazolium-5-olate) and 14 (3-benzyl-4-methyl-2-phenyl-1,3-oxazolium-5-olate) react with the N-protected 2- and 3-nitroindoles 1 (ethyl 2-nitroindole-1-carboxylate), 6 (3-nitro-1-(phenylsulfonyl)indole), and 17 (ethyl 3-nitroindole-1-carboxylate) in refluxing THF to afford in good to excellent yields the pyrrolo[3,4-b]indoles 15 (2-benzyl-1-methyl-3-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 16 (2-benzyl-3-methyl-1-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 18 (2-benzyl-1-methyl-3-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole), and 19 (2-benzyl-3-methyl-1-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole). In several cases the regiochemistry, which is opposite to that predicted by FMO theory, is very high and leads essentially to a single pyrrolo[3,4-b]indole; e.g., 6+13→19 in 74% yield.     

Condensation of aldehydes and ketones

The Mannich reaction with methylene- and benzylidenediacetophenones has given: 1,3-dibenzoyl-4-piperidinobutane, 1,3-dibenzoyl-4-morpholinobutane, 1,3-dibenzoyl-4-diethylamino-2-phenylbutane, 1,3-dibenzoyl-2-phenyl-4-piperidinobutane, 1,3-dibenzoyl-4-diethylaminobutane, and 1,3-dibenzoyl-4-dimethylamino-2-phenylbutane. From the latter two compounds, 3-diethylaminomethyl-2,6-diphenylpyridine and 3-dimethylaminomethyl-2,4,6-triphenylpyridine have been obtained.For part XVII, see [7].     

Oxidation of 1,3-Dioxacycloalkanes with Dimethyldioxirane

The kinetic regularities of the reactions of dimethyldioxirane with 1,3-dioxane, 2-propyl-, 2-isopropyl-, 2-phenyl-, 2,2-pentamethylene-, 2,2-dimethyl-, and 4-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolanes, as well as with 2-isopropyl-, 2-phenyl-, 2,2,4-trimethyl-, 2-isopropyl-4-methyl-, 4-methyl-, 4-methyl-2-phenyl-, and 5,5-dimethyl-2-phenyl-1,3-dioxanes in acetone were studied by spectrophotometry. The reaction kinetics are described by a second-order equation (first order in dioxirane and first order in dioxacycloalkane). The reaction rate is independent of the concentration of oxygen in the reaction mixture. The activation parameters of the reactions were determined.     

Studies in ring-opening polymerization. IV. Thermal polymerization of phenyl-substituted 1,3-dioxolan-2,4-diones

The effect of C-5 phenyl substituents on the thermal decomposition of the 1,3-dioxolan-2,4-dione ring has been examined. Unlike the dimethyl-substituted ring, 5-methyl-5-phenyl-1,3-dioxolan-2,4-dione decomposes smoothly in dry nonhydroxylic solvents to yield polymer and carbon dioxide. The introduction of a second C-5 phenyl substituent produces a similar but more rapid decomposition, with the added complication of a competing ring fragmentation leading to ketone formation. An analogy is drawn between the observed behavior of the phenyl-substituted 1,3-dioxolan-2,4-diones and that of the previously studied 1,3,2-dioxanthiolan-4-one 2-oxides. These monomers therefore provide another example of the thermal polymerisation mechanism first observed with 5,5-dimethyl-1,3,2-dioxathiolan-4-one 2-oxides. In these reactions the rate-determining step is the first-order ring-scission process leading to the formation of an α-lactone intermediate. This intermediate then takes part in a very rapid chain-growth process which governs the characteristics of the polymer formed.     

Photochemical synthesis of a 4,5-dihydrofuroazetidinone, a novel β-lactam system

2,4-Dimethyl-3-phenylisoxazole anhydrobases were easily prepared from the corresponding 5-chloroisoxazolium trifluoromethanesulfonate and carbon anions of 1,3-dioxo compounds in the presence of triethylamine. Photorearrangement of 2-(2,4-dimethyl-3-phenyl-2H-isoxazol-5-ylidene)malonic acid diethyl ester gave a 4,5-dihydrofuroazetidinone in good yield.     

Reactions with Hydrazonoyl Halides 611: Synthesis of 2,3-Dihydro-1,3,4-Thiadiazoles

2-[1,2-Diaza-3-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))prop-2-enylidene]-3-phenyl-5-substituted 1,3,4-thiadiazolines and 2-{[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]cyanomethylene}-3-phenyl-5-substitu- ted 1,3,4-thiadiazolines were synthesized from hydrazonoyl halides and 4-{-2-aza-2-[(methylthiothioxomethyl)amino]vinyl}-2,3-dimethyl-1-phenyl-3-pyrazoin-5-one and 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl)-1,3-thiazol-2-yl]ethane-nitrile, respectively. All synthesize compounds were elucidated by elemental analysis, spectra, and alternative synthesis routes, whenever possible.     

Thermische Reaktionen mit 3-Phenyl-2H-azirinen; 1, 3-dipolare Cycloadditionen und En-Reaktionen

Benzonitrile p-nitrobenzylide ( 5 ) undergoes 1,3-dipolar cyclo-additions in the presence of 3-phenyl-2H-azirines ( 1 ), yielding in benzene at 0° 2-(p-nitrophenyl)-4,5-diphenyl-1,3-diazabicyclo[3.1.0]hex-3-enes ( 7 , scheme 2). Under the basic conditions of the reaction mixture, 7 a and 7 b are partially converted to 2-(p-nitrophenyl)-4,5-diphenyl-1,6-dihydropyrimidines ( 8a, b ) which are dehydrogenated by oxygen to the corresponding pyrimidines 9a and 9b , respectively. 3-Phenyl-2H-azirines ( 1 ) form, on heating at 145° in xylene in the presence of the azalactone 32 (2,4-diphenyl-Δ²-oxazolin-5-one), 4-(aziridin-2′-yl)-2,4-diphenyl-Δ²-oxazolin-5-ones ( 33 , scheme 11). 33 arises from an ene reaction of the enol form of 32 with 1 . Similar ene reactions are observed with the azirines 1 and dimedone ( 37 , scheme 12). Under the ene reaction conditions (xylene, 145°), the non-isolated intermediate primary adducts ( 38a and 38b ) undergo rearrangements of the vinylcyclopane-cyclopentene type to give 6,6-dimethyl-4-oxo-1,3-diphenyl-4, 5, 6, 7-tetrahydroisoindole ( 40 ) and 6, 6-dimethyl-4-oxo-3-phenyl-4, 5, 6, 7-tetrahedroindole ( 42 ), respectively.     

Substituted pyrimidines. II. 1,3-Dimethylisocytosine and related compounds

1,3-Dimethyl-1,2-dihydro-2-imino-4(3H)pyrimidinone (1,3-dimethylisocytosine) was prepared by methylation of 2-amino-3-methyl-4(3H)pyrimidinone and was degraded in alkaline solution to a mixture of 3-methyl-2-methylamino-4(3H)pyrimidinone, 1,3-dimethyl-2,4-(1H,3H)pyrimid-indione, 2-methylamino-l-methyl-4(1H)pyrimidinone, 1-methyl-2,4-(1H,3H)pyrimidindione and 3-methyl-2,4-(1H,3H)pyrimidindione. Thiation of the title compound gave both 1,2-dihydro-1,3-dimethyl-2-thio-4(3H)pyrimidinone and 1,3-dimethyl-2,4-(1H,3H)pyrimidinedithione. The title compound is a tautomerically fixed pyrimidine and its uv spectra were compared with related compounds, notably 3-methyl-2-dimethylarnino-4(3H)pyrimidinone which is also tautomerically fixed.     

[f]-Fused purine-2,6-diones: Synthesis of new [1,3,5]- and [1,3,6]-thiadiazepino-[3,2-f]-purine ring systems

Summary 6-Phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,8,9-hexahydro-[1,3,5]-thiadiazepino-[3,2-f]-purine (5) was obtained by a three-step synthesis from 8-mercapto-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (1) and 2-(benzoylamino)-ethyl chloride (2)via 8-(benzoylaminoethylthio)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (3) and its chloromido derivative4. The analogous 9-phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,6,7-hexahydro-[1,3,6]-thiadiazepino-[3,2-f]-purine (7) was synthesized either from compound1 and N-(2-chloroethyl)-benzimido chloridevia N-(chloroethyl)-S-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-7H-purin-8-yl)-benzothioimide (6), or alternatively from 7-(2-benzoylaminoethyl)-8-bromo-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (9), its 8-mercapto derivative10 and the corresponding chloroimido compound11 being the intermediates.Part of this paper was presented as a preliminary report at the Congress of Czech and Slovak Chemical Societies, Olomouc, Czech Republic, September 13–16, 1993     

First direct detection of 2,3-dimethyl-2,3-diphenylcyclopropanone

3,5-dihydro-3,5-dialkyl-3,5-diaryl-4H-pyrazol-4-ones stimulate interest as potential precursors for 2,3-diarylcyclopropanones. Photoreactions of trans-3,5-dihydro-3,5-dimethyl-3,5-diphenyl-4H-pyrazol-4-one were studied by continuous-wave (CW) and pulsed laser UV photolysis revealing an intermediate that undergoes rearrangement to form cis- and trans-1,3-dimethyl-1-phenyl-2-indanones with the yield of ca. 60%. Steady-state photolysis (254 and 350 nm excitation) in different solvents produced an intermediate cyclohexadiene as evidenced by UV/vis, IR, and 1H NMR spectra. In contrast, the nanosecond laser pulsed photolysis at 355 nm produced 2,3-dimethyl-2,3-diphenylcyclopropanone along with two products of retro-1,3-dipolar addition phenylmethylketene and 1-phenyldiazoethane. These can be observed by time-resolved IR (TRIR) spectroscopy as characteristic absorption bands at 1814, 2101, and 2038 cm-1, respectively. Similar retro-1,3-dipolar addition showed 1-phenyldiazoethane formed following flash photolysis of 1-pyrazoline (trans-4,5-dihydro-3,5-dimethyl-3,5-diphenyl-3H-pyrazol-4-ol). The formation of the corresponding cyclopropanone as well the products of retro-1,3-dipolar addition during photoreaction of starting pyrazol-4-one is directly confirmed by the nanosecond TRIR spectroscopy for the first time. On the basis of the CW and pulsed laser UV photolysis, a dynamic equilibrium between cyclopropanone and intermediate 2,4-diphenyl-3-pentanone-2,4-diyl (dimethyldiphenyloxyallyl) was proposed.