Heteroannulation of 6-polyfluoroalkyl-2-thiouracils

A multi-component double Mannich cyclocondensation of 6-polyfluoroalkyl-2-thiouracils with formalin and heterocyclic amines (2-aminopyridine, 2-aminopyrimidine, 4-aminoantipyrine) proceeded regiospecifically at the C=S and NH centers giving rise to 3-hetaryl-8-polyfluoroalkylpyrimido[2,1-b][1,3,5]thiadiazines. The regioisomeric structure of the products was established by X-ray crystallography, IR and NMR spectroscopy, GLC-MS spectrometry. 6-Trifluoromethyl-2-thiouracil and 8-polyfluoroalkylpyrimido[2,1-b]thiadiazines exhibited weak tuberculostatic activity.     

Synthesis and Functionalization of 5-Alkyl-6-methyl-2-thiouracils

Russian Journal of General Chemistry - A number of 5-alkyl-6-methyl-2-thiouracils were obtained, the further introduction of which into the reaction with dialkyl chloroethynylphosphonates afforded...     

Intramolecular cyclization of 1-allyl- and 1-methallyl-6-amino-2-thiouracils

Intramolecular cyclization of 1-allyl- and 1-methallyl-6-amino-2-thiouracils afforded 5-amino-2,3-dihydrothiazolo[3,2-a]pyrimidin-4-ones, whose structures were proved by chemical transformations. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1694–1696, July, 2005.     

Alkylation of 4-hydroxy-6-methyl-2-methylthio-pyrimidine with chloroacetonitrile

The sodium salt of 4-hydroxy-6-methyl-2-methylthiopyrimidine is alkylated with chloroacetonitrile in hexamethyltriamidophosphate on the O-atom, and in dioxane or tetrahydrofuran on the N₃-atom, with the formation of 6-methyl-2-methylthio-4-cyanomethoxypyrimidine and 6-methyl-2-methylthio-3-cyanomethyl-4-pyrimidone, respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1525–1527, November, 1992.     

Synthesis,Phosphonylation, and Anti-Viral Activity of Some 6-Aryl-5-cyano-2-thiouracils

Russian Journal of General Chemistry - A series of 6-aryl-5-cyano-2-thiouracils was synthesized, the reaction of which with diethyl chloroethynylphosphonate leads to the selective formation of new...     

Reaction of S-allyl and propargyl derivatives of 2-thiouracils with hydrobromic acid

Hydrobromic acid reacts with 2-methallylthio- and 2-prenylthio-4(3Н)-pyrimidinones with participation of the double bond to give the products of heterocyclization, and with 2-allylthio- and 2-propargylthio-6-methyl-4(3Н)-pyrimidinones, with the retention of the double bond and the formation of hydrobromides.     

2-Aryl-6-Polyfluoroalkyl-4-Pyrones as Promising RF-Building-Blocks: Synthesis and Application for Construction of Fluorinated Azaheterocycles

A convenient and general method for the direct synthesis of 2-aryl-6-(trifluoromethyl)-4-pyrones and 2-aryl-5-bromo-6-(trifluoromethyl)-4-pyrones has been developed on the basis of one-pot oxidative cyclization of (E)-6-aryl-1,1,1-trifluorohex-5-ene-2,4-diones via a bromination/dehydrobromination approach. This strategy was also applied for the preparation of 2-phenyl-6-polyfluoroalkyl-4-pyrones and their 5-bromo derivatives. Conditions of chemoselective enediones bromination were found and the key intermediates of the cyclization of bromo-derivatives to 4-pyrones were characterized. Synthetic application of the prepared 4-pyrones has been demonstrated for the construction of biologically important CF₃-bearing azaheterocycles, such as pyrazoles, pyridones, and triazoles.     

Alkylation of 2-methylimidazole with iodomethylsilanes

2-Methyl-1,3-bis[(1-methylsilolan-1-yl)methyl]-1H-imidazolium triiodide, 1,3-bis{[dimethyl-(phenyl)silyl]methyl}-2-methyl-1H-imidazolium iodide and triiodide, and cyclic 3,3,5,5,10-pentamethyl-4-oxa-7-aza-1-azonia-3,5-disilabicyclo[5.2.1]deca-1(10),8-diene iodide were synthesized by solvent-free reactions of 2-methyl-1H-imidazole with 1-(iodomethyl)-1-methylsilolane, (iodomethyl)(dimethyl)phenylsilane, and ethynyl(iodomethyl)(dimethyl)silanes, respectively, in the absence of base catalyst.     

6-Amino-2-thio- and 6-Aminouracils as Precursors for the Synthesis of Antiviral and Antimicrobial Methylenebis(2-thiouracils), Tricyclic Pyrimidines,and 6-Alkylthiopurine-2-ones

Summary. Several derivatives of 5-arylmethylenebis(1-methyl-6-amino-2-thiouracils) and 5-aryldipyrimidopyridines were prepared by stirring of 6-amino-1-methyl-2-thiouracil and 6-amino-1-benzyluracil with different aromatic aldehydes in ethanol in the presence of HCl or refluxing with AcOH. On the other hand, 6-alkylthio-3,9-dimethylpurine-2-ones were synthesized by the alkylation of 3,9-dimethyl-6-thioxanthine which was prepared by treatment of 3,9-dimethylxanthine with P₂S₅. The structures of the novel compounds were characterized by spectroscopic methods. The effects of the novel compounds on both HAV and HSV type 1 were investigated. Also, some compounds showed inhibitory effects on Gram-positive and Gram-negative bacteria as well as yeast and fungi. On leave from Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt     

Synthesis and anti-HIV-1 activity of 1,5-dialkyl-6-(arylselenenyl)uracils and -2-thiouracils

The 1,5-dialkyl-6-(arylselenenyl)uracils 10a-h and -2-thiouracils 10i-p have been synthesized as potential anti-HIV-1 agents. Cyclization of N-alkyl-N'-[3,3-di(methylthio)-2-alkylacryloyl]ureas 6a-d and -thioureas 6e-h in acetic acid either containing a catalytic amount of methanesulfonic acid at 80°or containing 1 equivalent of methanesulfonic acid at room temperature afforded 1,5-dialkyl-6-(methylthio)uracils 7a-d in 84–96% yields and 1,5-dialkyl-5,6-dihydro-6,6-di(methylthio)-2-thiouracils 11a-d in 88–99% yields, respectively. Oxidation of 7a-d and 11a-d with either 3-chloroperoxybenzoic acid in benzene or aqueous sodium periodate solution in methanol gave 1,5-dialkyl-6-(methylsulfonyl)uracils 8a-d in 88–98% yields and 1,5-dialkyl-6-(methylsulfinyl)-2-thiouracils 12a-d in 57–73% yields, respectively, which were subsequently treated with arylselenol 9a-b in ethanolic sodium hydroxide solution to afford 10a-p in 6099% yields. Of these compounds, 6-[(3,5-dimethylphenyl)selenenyl]-5-isopropyl-1-(3-phenylpropyl)uracil ( 10h ) inhibited HIV-1 replication in MT-4 cells at a 50% effective concentration (EC₅₀) of 0.0006 μM with a selective index of 44833, which is 7.7-fold more potent than AZT.     

Unimolecular photochemistry of 4-thiouracils

Unimolecular phototautomeric reactions in 4-thiouracil, 1-methyl-4-thiouracil and 6-aza-4-thiouracil were studied using the matrix-isolation technique combined with infrared absorption spectroscopy. For monomers of these compounds, isolated in solid argon at 10 K, an intramolecular proton-transfer photoreaction was observed. Upon UV (lambda > 345 nm) irradiation, the initial oxo-thione forms of 4-thiouracils were converted into the corresponding oxo-thiol tautomers. The photogenerated oxo-thiol isomers were identified by comparing their experimental IR spectra with the spectra theoretically calculated at the DFT(B3LYP)/6-311++G(2d,p) level. Good agreement between the observed and predicted pattern of spectral bands allowed a reliable identification. This is the first report on experimental observation of isomeric forms of 4-thiouracils other than the canonical oxo-thione tautomers.     

Alkylation of aromatic hydrocarbons with 2-bromo-2-phenyl-gem-dichlorocyclopropane

The alkylation of aromatic hydrocarbons with 2-bromo-2-phenyl-gem-dichlorocyclopropane in the presence of catalytic quantities of aluminum chloride was found to afford the corresponding 2-aryl-3-phenyl-1,1-dichloroprop-1-enes. It was shown that the yield of the alkylation products depended on the nature of substituents in the aromatic ring. Compared with the thermal heating, microwave irradiation allows reducing the reaction time and increasing the yield of the corresponding 2-aryl-3-phenyl-1,1-di-chloroprop-1-enes, wherein the ortho-/para-isomers ratio changes.     

Alkylation of 2-aminothiazoles

Alkylation of 3,4-dimethylthiazolon-2-imide with isopropanol or tert-butanol gives 3,4-dimethyl-5-alkylthiazolon-2-imides in up to 60% yield. Acyl derivatives are prepared.For Part V see [5].     

Alkylation of 2-ammopyridine

Alkylation of 2-aminopyridine with cyclohexanol or isopropanol in sulfuric acid gives yields of up to 70% of 2-alkylaminopyridines.