<Emphasis Type="Italic">S</Emphasis>-functional derivatives of 3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>-1,4-thiasilines

The first cyclic unsaturated S-functional derivatives of 4,4-diphenyl-3,4-dihydro-2H-1,4-thiasiline, S-oxide, S,S-dioxide, and S-sulfonimide, were prepared. Oxidation of the hydrolytically less stable 4,4-dimethyl-3,4-dihydro-2H-1,4-thiasiline leads to the corresponding sulfoxide and sulfone along with the ring opening products, siloxanes containing the sulfoxide or sulfonyl group.     

Regioselective synthesis of polyfluoroalkyl-substituted 7-(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-1-yl)-6,7-dihydro-1<Emphasis Type="Italic">H</Emphasis>-indazol-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

3-Polyfluoroalkyl-6,6-dimethyl-7-(1H-1,2,3-triazol-1-yl)-6,7-dihydro-1H-indazol-4(5H)-ones were synthesized with high regioselectivity by 1,3-dipolar cycloaddition of terminal alkynes (phenylacetylene, hex- 1-yne, hept-1-yne, and but-3-yn-1-ol) to 7-azido-6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol-4(5H)-ones which were prepared by bromination of 6,6-dimethyl-3-polyfluoroalkyl-6,7-dihydro-1H-indazol- 4(5H)-ones with N-bromosuccinimide in anhydrous carbon tetrachloride, followed by treatment of the corresponding 7-bromo derivatives with sodium azide.     

Synthesis of isoxazole derivatives of 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole

Cyclocondensation of pent-1-en-4-yn-3-one with phenylhydrazine and p-tolylhydrazine occurs at the positions 1, 3. Proceeding from the 1-aryl-3-ethynyl-4,5-dihydro-1H-pyrazoles formed in the reaction in yields up to 95% we prepared potentially biologically active isoxazole derivatives of pyrazoline. The structure of 5-[1-(4-methylphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-3-phenyl-1,2-oxazole was studied by X-ray diffraction analysis.     

New synthesis of 5,5-dimethyl-3-oxo-4,5-dihydro-3<Emphasis Type="Italic">H</Emphasis>-pyrrole 1-oxide

A procedure has been developed for the synthesis of 5,5-dimethyl-3-oxo-4,5-dihydro-3H-pyrrole 1-oxide via oxidation of 2,2,6,6-tetramethyl-4-oxopiperidine 1-oxyl with chlorine in aqueous sodium perchlorate and subsequent ring contraction in the resulting 2,2,6,6-tetramethyl-1,4-dioxopiperidinium perchlorate in dilute perchloric acid. The relative rates of proton exchange between the CH₂ and CH groups in the title compound were determined by ¹H NMR spectroscopy in D₂O, and the acidity constant was estimated on the basis of the dependence of the UV spectrum upon pH (pK _a = 13.2).     

Nitration of 1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-one derivatives

Nitration of 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one and its N-methyl derivatives at 0–5°C and 60°C gives 5-nitro-and 5,6-dinitro-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones, respectively. The latter can also be obtained by nitration of 5-mononitro derivatives under similar conditions. The nitration of 6-chloro-and 6-bromo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones and their N-methyl-substituted analogs leads to the formation of the corresponding 6-chloro(bromo)-5-nitro compounds. The same products are formed in the nitration of 5,6-dichloro-and 5,6-dibromo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones. In this case, the process involves replacement of the halogen atom in position 5 of the pyridine fragment by nitro group. The nitration of 6-bromo-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one is accompanied by oxidation of the 5-methyl group to carboxy.     

3-(4,5-Dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-ylmethyl)oxazolidines and 3-(4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-ylmethyl)perhydro-1,3-oxazines

3-(4,5-Dihydro-1H-pyrazol-1-ylmethyl)oxazolidines and 3-(4,5-dihydro-1H-pyrazol-1-ylmethyl)perhydro-1,3-oxazines were synthesized in 54–85% yield by reactions of α-amino alcohols and 3-aminopropan-1-ol, respectively, with formaldehyde and 4,5-dihydro-1H-pyrazoles.     

Recyclization of 1,3-dialkyl-6-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,5(3<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>)-diones into imidazole derivatives

Treatment of 5-amino-1,3-dialkyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones with sodium nitrite in aqueous HCl gave 1,3-dialkyl-1H-imidazo[4,5-b]pyridine-2,5(3H,4H)-diones which were nitrated with potassium nitrate in sulfuric acid to 6-nitro derivatives, and the latter underwent recyclization into 4-amino-1,3-dialkyl-5-(1H-pyrazol-5-yl)-2,3-dihydro-1H-imidazol-2-ones by the action of hydrazine hydrate.     

Tautomerism of azacycles: III. Molecular and crystal structures of 3<Emphasis Type="Italic">H</Emphasis>-and 2-phenyl-1<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>-4,5-dihydro-1,2,4-triazole-5-thiones

Compounds capable of tautomerism: sulfanyl-1,2,4-triazole, its C-phenyl derivative, and the crystal hydrate of the latter, were studied by single crystal X-ray diffraction. In the crystals they exist in the form of 3-R-1(H),4(H)-4,5-dihydro-1,2,4-triazole-5-thione with a considerable contribution of the bipolar structure. Published data on the tautomerism of sulfanyl-1,2,4-triazoles and their N-substituted analogs and on the correlation between the spectral characteristics and structures of sulfanyl-1,2,4-triazoles capable of tautomerism are discussed.     

Carboxamides of Dihydropyridin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

Summary. 3-Carboxamides and 3-carboxanilides of 6-alkyl and 6-aryldihydropyridin-2(1H)-ones have been prepared via different reaction pathways. All synthesized amides show hydrogen bonds in their NMR spectra. The 4-hydroxy compounds were obtained as a mixture of tautomers. Their configurations were elucidated by NMR experiments.Received December 16, 2002; accepted December 20, 2002 Published online June 2, 2003     

Enantioselective microbial synthesis of (<Emphasis Type="Italic">S</Emphasis>)-7,8-difluoro-3,4-dihydro-3-methyl-2<Emphasis Type="Italic">H</Emphasis>-[1,4]benzoxazine

New strains of Rhodococcus erythropolis 25 and Microbacterium paraoxydans 20-11c actinobacteria were used to obtain (S)-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (99.6% ee) by enantioselective microbial hydrolysis of the corresponding racemic N-acetyl derivative.     

3-aryl(alkyl)quinazoline-2,4(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>)-diones and their alkyl derivatives

Two-stage reaction of methyl anthranilate with aryl(alkyl) isocyanates in keeping with the quantumchemical calculations and XRD analysis resulted in 3-aryl(alkyl)quinazoline-2,4(1H,3H)-diones that by treatment with alkyl halides, phenacyl bromides, esters and amides of chloroacetic acid were converted into the corresponding 1-alkyl derivatives.     

<Emphasis Type="Italic">C</Emphasis>(2)-Functionalization of pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-one derivatives in the synthesis of its biologically active derivatives

Different approaches to the formation of biologically active isocytosine, uracil, and 2-thiouracil derivatives based on the C(2)-regioselective functionalization of pyrimidin-4(3H)one framework were considered.     

Alkylation of 2-(hydroxyimino)-5<Emphasis Type="Italic">H</Emphasis>-[1,3]thiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]-pyrimidin-3(2<Emphasis Type="Italic">H</Emphasis>)-ones

Alkylation products were obtained from ethyl 2-(hydroxyimino)-7-methyl-3-oxo-5-aryl-2,3- dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-6-carboxylates at the treatment with alkyl halides, dimethyl sulfate, and diazomethane. Diazomethane alkylated the initial substrate at the oxygen atom of the carbonyl group of the thiazolidine fragment, the other reagents, at the oxygen atom of the hydroxyimino group.     

Synthesis of carbamate derivatives of 2,3-dihydro-4<Emphasis Type="Italic">H</Emphasis>-1,4-benzoxazine

Alkylation of methyl 2-hydroxyphenylcarbamates with 1,2-dibromoethane in acetone in the presence of K₂CO₃ gave the corresponding methyl 6(7)-R-2,3-dihydro-4H-1,4-benzoxazine-4-carboxylate. Alkylation of methyl 2-hydroxyphenylcarbamates with chloromethyloxirane was accompanied by recyclization of the oxirane ring with formation of methyl 6(7)-R-3-hydroxymethyl-2,3-dihydro-4H-1,4-benzoxazine-4-carboxylates.     

Reaction 5-(Arylmethylidene)pyrimidine-2,4,6(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>,5<Emphasis Type="Italic">H</Emphasis>)-triones with L-Proline and Aldehydes

Boiling in toluene of 5-(arylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-triones with L-proline and aldehyde led to the formation of previously unknown substituted 1′-arylhexahydro-1H-spiro[pyrimidine-5,2′-pyrrolysine]-2,4,6(1H,3Н,5Н)-triones.     

Synthesis and biotests of 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4<Emphasis Type="Italic">H</Emphasis>)-ones and <Emphasis Type="Italic">N</Emphasis>-methyl-3,5-dihydro-4<Emphasis Type="Italic">H</Emphasis>-imidazol-4-ones as combretastatin A-4 analogs

A series of 2-aryl-5-arylmethylidene-1,3-oxazol-5(4H)-ones and 2-aryl-5-arylmethylidene-N-methyl-3,5-dihydro-4H-imidazol-4-ones was synthesized as structural analogs of combret- astatin A-4 (a compound possessing antitumor activity). (5Z)-5-[(4-Methoxyphenyl)methyl-idene]-3-methyl-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one was found to exhibit the highest cytotoxicity against cells of human A549 lung carcinoma line (EC₅₀ = 6±0.8 μmol L^?1).     

Chemistry of 2-ylidenefuran-3(2<Emphasis Type="Italic">H</Emphasis>)-ones: XIX. Reaction of 5-aryl-2(oxoylidene)furan-3(2<Emphasis Type="Italic">H</Emphasis>)-ones with carboxylic acid hydrazides

2-[2-(4-Chlorophenyl)-2-oxoethylidene]-5-phenylfuran-3(2H)-one and methyl (5-aryl-3-oxo-2,3-dihydrofuran-2-ylidene)acetates react with carboxylic acid hydrazides to give the corresponding 3-substituted 2-acyl-6-aryl-3-hydroxy-2,3-dihydropyridazin-4(1H)-ones. Specificities of the product structure are discussed.     

Reaction of 5-arylfuran-2(3<Emphasis Type="Italic">H</Emphasis>)-ones with amines

5-(4-Chlorophenyl)- and 5-phenylfuran-2(3H)-ones reacted with guanidine carbonate at the methylene group in the unsaturated lactone molecule, leading to the formation of 4-(2-aryl-5-oxo-2,5-dihydrofuran-2-yl)-5-aryltetrahydrofuran-2-ones, while 5-(4-methylphenyl)furan-2(3H)-one under analogous conditions gave rise to N,N′-bis[4-(4-methylphenyl)-4-oxobutanoyl]guanidine. The reactions of 5-arylfuran-2(3H)- ones with thioacetamide afforded 4-aryl-N-{1-[5-aryl-2-oxo-2,3-dihydrofuran-3-ylidene]ethyl}-4-oxobutanamides. The corresponding N-(4-aryl-4-oxobutanoyl)thioureas were obtained by heating 5-arylfuran-2(3H)-ones with thiourea.