Synthesis of 5-Alkyl(aryl)-2-alkylsulfanyl(alkoxy)-4-hydroxy-6H-1,3-oxazin-6-ones

Alkyl carbamates and S-alkyl thiocarbamates react with substituted malonyl dichlorides in boiling benzene to give the corresponding 2,5-substituted 4-hydroxy-6H-1,3-oxazin-6-ones. The reaction of S-methyl thiocarbamate with unsubstituted malonyl dichloride in boiling diethyl ether or benzene leads to formation of S-methyl (3-methylsulfanylaminocarbonyl-3-oxopropionyl)thiocarbamate and is not accompanied by cyclization, whereas in boiling toluene 4-hydroxy-2-methylsulfanyl-6H-1,3-oxazin-6-one is obtained.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005, pp. 468–472.Original Russian Text Copyright © 2005 by Lalaev, Yakovlev, Zakhs.     

Reactions of 4-Hydroxy-5-methyl(phenyl)-2-styryl-6H-1,3-oxazin-6-ones with Nucleophiles

4-Hydroxy-5-methyl(phenyl)-2-styryl-6H-1,3-oxazin-6-ones react with hydrazine and phenylhydrazine to give the corresponding 3,5-substituted triazoles. Treatment of the title compounds with ethanol and methanol leads to formation of N-cinnamoylmalonamates. The structure of the products was confirmed by the IR and ¹H and ¹³C NMR spectra.     

First preparation and reaction of polymer-bound 1,2-diaza-1,3-butadienes. A convenient entry to 4-triphenylphosphoranylidene-4,5-dihydropyrazol-5-ones

The first general protocol for the preparation of different polymer-bound 1,2-diaza-1,3-butadienes is reported. The utility of these supported reagents in the solid-phase synthesis of 4-triphenylphosphoranylidene-4,5-dihydropyrazol-5-ones by reaction with triphenylphosphine is presented.     

Preparative synthesis of 4-methyl-2-(trifluoromethyl)-1,3-oxazin-6-one

Russian Chemical Bulletin -     

Synthesis of 1,3-dialkyl-5-(hetaryl-1-yl)-1,3-dihydrobenzimidazol-2-ones

Reactions of 5-amino-1,3-dialkyl-1,3-dihydrobenzimidazol-2-ones with 2,5-dimethoxytetrahydrofuran and 2,6-dimethyl-γ-pyranone led to the formation of 1,3-dialkyl-1,3-dihydro-5-(pyrrol-1-andл)benzimidazol-2-ones and 1-(1,3-dialkyl-2-oxo-1,3-dihydrobenzimidazol-5-yl)-2,6-dimethylpyridin-4-ones.     

Synthesis and biological evaluation of novel 2-(substituted isoxazol-4-yl)-5-arylamino-1,3,4-oxadiazoles

A series of 2-(5-methyl-3-(4-chloro/trifluoromethylphenyl)isoxazol-4-yl)-5-arylamino-1,3,4-oxadiazoles were synthesized from 4-chloro/trifluoromethyl benzaldehyde, ethyl acetoacetate, hydroxylamine hydrochloride, hydrazine hydrate, and aryl isocyanate by multi-step reactions. The structures of the target compounds were elucidated by IR, ¹H NMR, MS, and elemental analysis. All these compounds were tested for in vitro antifungal activities against Botrytis cinerea and Rhizoctonia cerealis by the mycelium growth rate method, and the results indicated that some compounds displayed high antifungal activity against Botrytis cinerea.     

Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.     

Enantiocatalytic activity of substituted 5-benzyl-2-(pyridine-2-yl)imidazolidine-4-one ligands

Currently, asymmetric synthesis represents one of the main streams of organic synthesis. Although an extensive research has been carried out in this area, the synthesis of chiral compounds with the required enantiomeric purity is still a challenging issue. Herein, we focus on the preparation of new enantioselective catalysts based on pyridine-imidazolidinones. The substituted 5-benzyl-2-(pyridine-2-yl)imidazolidine-4-ones 5–8 were prepared by condensation of chiral amino acid amides (α-methylDOPA and α-methylphenylalanine) with 2-acetylpyridine and pyridine-2-carbaldehyde. The individual isomers of the described ligands 5–8 were separated chromatographically. The copper(II) complexes of these chiral ligands were studied as enantioselective catalysts for the asymmetric Henry reaction of substituted aldehydes with nitromethane or nitroethane. The ligands containing a methyl group at the 2-position of the imidazolidinone ring 6a and 8a exhibit a high degree of enantioselectivity (up to 91% ee). The nitroaldols derived from nitroethane (2-nitropropan-1-ols) were obtained with a comparable enantiomeric purity to derivatives of 2-nitroethanol. This group of ligands represents a new and promising class of enantioselective catalysts, which deserve further attention.     

Synthesis of new 1,3-thiazole derivatives from 2(5)-hydroxyalkyl-1,3-thiazole-5(2)-carbaldehydes

Reactions of substituted 2-hydroxyalkyl-1,3-thiazole-5-carbaldehydes and 5-hydroxyalkyl-1,3-thiazole-2-carbaldehydes with phenylhydrazine, isoniazid, N-substituted rhodanines were performed as well as Biginelli reaction with acetoacetic ester and urea. As a result, new 1,3-thiazole derivatives were obtained. They are of interest as potential bioactive substances.     

Recyclization of 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydro-pyridin-2-ones into 1,6-annelated derivatives of 3-alkylcarbamoyl-5-benzoylpyridin-2-one

For the first time the possibility has been shown of recyclizing 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones into 1,6-annelated bicyclic derivatives of 3-alkylcarbamoyl-5-benzoylpyridin-2-one, which takes place on reacting the former with 1,4- and 1,5-nitrogen-containing dinucleophiles. The structure of the recyclization products was demonstrated by spectral methods and X-ray structural analysis.     

Efficient synthesis of new chiral 1,2-benzothiazin-3-one 1,1-dioxide derivatives via lateral lithiation of 3-N-mesitylenesulfonyl-1,3-oxazolidin-2-ones

Chiral 3-N-mesitylenesulfonyl-1,3-oxazolidin-2-ones 4a-e derived from (l)- and (d)-amino acids 1a-e undergo lateral lithiation with lithium diisopropylamide and TMEDA in anhydrous THF to provide new optically-active 1,2-benzothiazin-3-one 1,1-dioxide derivatives 5a-e with yields ranging from 63% to 79%.     

Ring opening of 2-(bromomethyl)-1-sulfonylaziridines towards 1,3-heteroatom substituted 2-aminopropane derivatives

1,3-Heteroatom substituted 2-aminopropane derivatives have been prepared from 2-(bromomethyl)-1-sulfonylaziridines for the first time using sodium azide or different potassium phenoxides in water in the presence of silica gel. The applicability of 1-arenesulfonyl-2-(bromomethyl)aziridines for the synthesis of functionalized sulfonamides has also been demonstrated towards different 1,3-dialkoxy-2-(tosylamino)propanes and 1,3-dialkylthio-2-(tosylamino)propanes upon treatment with the appropriate sodium alkoxide or sodium alkylthiolate in the corresponding alcohol or in methanol, respectively.     

A convenient method for the synthesis of 2-[(5-benzyl-1,3-thiazol-2-yl)imino]-1,3-thiazolidin-4-one derivatives

It was found that the reaction of 2-chloroacetamido/chloropropioamido-5-benzylthiazole with potassium thiocyanate gave, via rearrangement, 2-[(5-benzyl-1,3-thiazol-2-yl)imino]-1,3-thiazolidin-4-ones.     

Synthesis and anti-proliferative activity studies of 2-(2-(trifluoromethyl)-6-(substituted)imidazo[1,2-b]pyridazin-3-yl)-N-(substituted)acetamide derivatives

A series of novel imidazo[1,2-b]pyridazin-3-yl acetamide derivatives (9a-9j) were synthesized from a 3,6-dichloropyridazine. We have developed a simple strategy for the synthesis of functionally diverse imidazole, and pyridiazine derivatives were reported via a series of steps. The work involves bicyclic imidazo-pyridazine ring formation, halogenation, cynation, hydrolysis, peptide coupling, and Buchwald reaction. The structure of the synthesized compounds was confirmed by IR, ¹H NMR, ¹³C NMR,¹⁹F NMR, mass spectra, and elemental analysis, and purity is checked by HPLC. All synthesized compounds were screened for anticancer activity against A-549 and Du-145 cancer cell lines by MTT assay. The preliminary bioassay suggests that most of the compounds show anti-proliferation with different degrees; doxorubicin was used as positive control. The synthesized compound shows IC₅₀ values in the range of 1.74μM to 16.17μM in both cell lines. The compounds 9e , 9g , and 9h were active compared with doxorubicin in both the cell lines. The compounds having cyclopentyl ring are active compared with higher and lower carbon analogues.     

Aldol addition of lithium and boron enolates of 1,3-dioxan-5-ones to aldehydes. A new entry into monosaccharide derivatives

Methods allowing control of stereoselectivity in aldol reactions of enolates derived from 1,3-dioxan-5-ones (4) are described. Boron enolates, generated in situ, react with benzaldehyde to give the corresponding anti aldol selectively (the anti:syn ratio of up to 96:4) and in high yield. Lithium enolates give high anti selectivity only with aldehydes branched at the alpha-position. Enantioselective deprotonation of C(S) symmetrical dioxanones (e.g., 4b) can be accomplished efficiently, with enantiomeric excess of up to 90%, with chiral lithium amide bases of general structure PhCH(Me)N(Li)R (9, 10) if the R group is sufficiently bulky (e.g, R = adamantyl) or is fluorinated (e.g., R = CH2CF3). Dioxanone boron and lithium enolates react readily with glyceraldehyde derivatives (19), yielding protected ketohexoses (20 and 21).     

Synthesis of 1,3-dialkyl-5-(pyrrol-1-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones

Russian Journal of Organic Chemistry -