Trifluoroacetylation of 3-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2-diazaphenalenes of the naphthalene and acenaphthene series

Acylation of 3-methyl-1H-1,2-diazaphenalenes of the naphthalene and acenaphthene series with trifluoroacetic anhydride afforded the corresponding N- and C-trifluoroacetyl derivatives and dimerization products of 3-methyl-6-methoxy-1H-1,2-diazaphenalene.     

Alkylation of 2-(methylsulfanyl)-6-polyfluoroalkylpyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones with haloalkanes

The alkylation of ambident anions of 2-(methylsulfanyl)-6-(polyfluoroalkyl)pyrimidin-4(3H)-ones with 4-bromobutyl acetate leads to concurrent formation of O- and N-(4-acetoxybutyl) derivatives. Polar aprotic solvents favor formation of the O-isomer, and weakly polar dioxane favors N-alkylation. The reaction of 2-(methylsulfanyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one with an equimolar amount of 1,2-dibromoethane in polar acetonitrile gives a mixture of N,N-, O,O-, and N,O-bridged bis-pyrimidines, as well as N- and O-[2-(methylsulfanyl)ethyl] derivatives, whereas in the presence of 10 equiv of 1,2-dibromoethane the N,O-isomer is formed as the only product. The reaction in weakly polar tetrahydrofuran yields N,N- and N,O-bispyrimidines.     

Synthesis of <Emphasis Type="Italic">ortho</Emphasis>-carboranyl derivatives of (<Emphasis Type="Italic">S</Emphasis>)-asparagine and (<Emphasis Type="Italic">S</Emphasis>)-glutamine

(S)-Asparagine and (S)-glutamine ortho-carboranyl derivatives with free amino and carboxy groups in the α-position were synthesized. By an example of N ^γ-(1,2-dicarba-closo-dodecarboran-3-yl)-(S)-glutamine it was demonstrated that the developed synthetic approach carboranyl derivatives of amino acids allowed the preparation of optically pure isomers.     

Stereochemistry of dihydroxylation of <Emphasis Type="Italic">N</Emphasis>-arylbicyclo[2.2.1]-hept-5-ene-<Emphasis Type="Italic">endo</Emphasis>- and -<Emphasis Type="Italic">exo</Emphasis>-2,3-dicarboximides

Stereochemistry of the oxidation of N-arylbicyclo[2.2.1]hept-5-ene-endo-and-exo-2,3-dicarboximides at the double bond with peroxyacetic acid generated in situ in the presence of sulfuric acid and with an anhydrous dioxane solution of peroxyacetic acid was studied. In both cases, the reaction was stereospecific, regardless of the substituent in the N-aryl group and configuration of the imide ring, but the reaction direction depended on the presence of water in the system. In the first case, the corresponding trans-5,6-dihydroxy derivatives were formed, while in the second, exo-5,6-epoxy derivatives. The oxidation of N-arylbicyclo[2.2.1]-hept-5-ene-endo-and-exo-2,3-dicarboximides with a solution of potassium permanganate in aqueous acetone gave the corresponding N-aryl-cis-5,6-dihydroxybicyclo[2.2.1]heptane-endo-and-exo-2,3-dicarboximides. The exo,cis,exo and exo,cis,endo configurations of the synthesized compounds were determined by ¹H NMR spectroscopy.     

Diels-alder reactions of alumina-and magnesacyclopentadienes

[4π + 2π]-Cycloaddition of substituted alumina-and magnesacyclopenta-2,4-dienes with such dienophiles as maleic anhydride, N-methylmaleimide, 1,4-benzoquinone, and 1,4-naphthoquinone resulted in the formation of the corresponding fused alumina-and magnesanorbornenes whose hydrolysis gave isobenzofuran, isoindole, naphthalene, and anthracene derivatives in high yields.     

New functionalization opportunities for <Emphasis Type="Italic">peri</Emphasis>-hydroxynaphthoyl and <Emphasis Type="Italic">peri</Emphasis>-fused heterocyclic compounds

A capability was studied of hydrogenated α-pyrone heterocycle in 7-methoxy-4-(4-methoxy-phenyl)-3,4-dihydro-2H-benzo[h]chromen-2-one to undergo aminolysis under the treatment with hydrazine hydrate, primary and secondary aliphatic and aromatic amines. A new approach was developed to the preparation of perihydroxyketone of naphthalene series containing a specific functional substituent in the ortho-position with respect to hydroxy group. The effect was revealed of an acetyl group in the position 9 of 7-methoxy-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[h]chromen-2-one on the reaction of this compound with aliphatic amines and hydrazine hydrate. 9-Methoxy-1-(4-methoxyphenyl)-6-methyl-3H-benzo[de]pyrido[3,2,1-if]cinnolin-3-one [9-methyl-6-methoxy-3-(4-methoxyphenyl)-10,10a-diazapyren-1-one] was obtained, a new bis-peri-fused heteroaromatic system.     

Regioselectivity in the reactions of <Emphasis Type="Italic">N</Emphasis>-(polychloroethylidene)-sulfonamides with 1<Emphasis Type="Italic">H</Emphasis>-pyrrole and 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrrole

N-(2,2,2-Trichloroethylidene)arenesulfonamides react with 1H-pyrrole and 1-methyl-1H-pyrrole to give the corresponding N-[2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethyl]arenesulfonamides. The reaction of N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide with pyrrole leads to a mixture of 2-mono-and 2,5-disubstituted pyrroles, whereas in the reaction with 1-methyl-1H-pyrrole only the 2-substituted compound is formed. N-(2,2-Dichloro-2-phenylethylidene)-4-methylbenzenesulfonamide reacts with 1H-pyrrole to form N-[2,2-dichloro-2-phenyl-1-(1H-pyrrol-2-yl)ethyl]-4-methylbenzenesulfonamide, and its reaction with 1-methyl-1H-pyrrole gives a mixture of 2-and 3-monosubstituted derivatives. The results of quantum-chemical calculations of the initial reactants and products indicate that the process is orbital-controlled. A good agreement is observed between the experimental data and theoretical conclusions concerning the dependence of the reaction regioselectivity on the nature of substituents in the electrophile molecule.     

Synthesis and in vitro antibacterial evaluation of 6-substituted 4-amino-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

Pyrazolo[3,4-d]pyrimidines are one of the most important classes of fused heterocyclic compounds which exhibit a broad range of biological and medicinal properties. They are known as anticancer, antifungal, antibacterial, antiviral and anti-inflammatory agents. In this study, some new 6-substituted 4-amino-pyrazolo[3,4-d]pyrimidine derivatives were prepared via reaction of 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carbonitrile with various nitriles in the presence of sodium ethoxide as catalyst. The inhibitory properties of synthesized compounds were studied according to CLSI guidelines against some pathogenic bacteria including four gram-positive strains (Streptococcus pyogenes, Staphylococcus aureus, Bacillus cereus and Bacillus subtilis subsp. spizizenii) and three gram-negative strains (Pseudomonas aeruginosa, Shigella flexneri and Salmonella enterica subsp. enterica). The antibacterial effects of all derivatives were compared with those of antibiotics belonging to different classes. The values were reported as inhibition zone diameter (IZD), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The effect of substituents on the biological activity of derivatives was discussed as well. The inhibitory effect of compound 6a, was shown to be the most, with MIC values in the range of 32–4096 μg/mL. Since most of the synthesized compounds were effective against Streptococcus pyogenes and Pseudomonas aeruginosa, they can be considered as inhibitors of these two bacteria.     

Synthesis and structural study of 3-phenyl-6,7,8,9-tetrahydrocyclopenta[<Emphasis Type="Italic">a</Emphasis>]naphthalene-containing <Emphasis Type="Italic">ansa</Emphasis>-complexes of zirconium

The zirconium rac- and meso-complexes of the ansa-type that contain a 3-phenyl-6,7,8,9-tetrahydrocyclopenta[a]naphthalene fragment and a dimethylsilylene bridge are synthesized. The compounds obtained are characterized by NMR spectroscopy; the structure of rac-complex is studied by X-ray diffraction, which maked it possible to evaluate the steric availability of the zirconium center in the corresponding catalysts for the olefin polymerization.     

Compounds of the menthane series. Synthesis of unsaturated primary alcohols with the <Emphasis Type="Italic">o</Emphasis>- and <Emphasis Type="Italic">p</Emphasis>-menthane skeletons

Precursors to terpene alcohols of the o- and p-menthane series (o-cimen-7-ol and o- and p-cimen-9-ols) were synthesized, and their reduction with lithium in ethylenediamine was studied. The reduction of o- and p-cimen-9-ols in the presence of isopropyl alcohol selectively afforded the corresponding 1,4-dihydro derivatives. Under analogous conditions, o-cimen-7-ol was converted into a mixture of unsaturated hydrocarbons. The reduction with lithium in ethylenediamine in the absence of isopropyl alcohol in all cases gave mixtures of menthene alcohols.     

Synthesis of oxo derivatives of <Emphasis Type="Italic">N</Emphasis>-(<Emphasis Type="Italic">p</Emphasis>-tolysulfonyl)hexahydrocycloalka[<Emphasis Type="Italic">b</Emphasis>]indoles

Hydroxymercuration-demercuration of N-p-tolysulfonyl-4,4a,9,9a-tetrahydro-3H-carbazoles and N-p-tolyl(or methyl)sulfonyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles leads to the formation of the corresponding N-p-tolylsulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-2-ols and N-p-tolyl(or methyl)sulfonyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indol-2-ols. The latter are oxidized to 2-oxo derivatives with potassium dichromate. The oxidation of 2-methoxy-8-methyl-N-p-tolylsulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-1-ol under analogous conditions gives 2-methoxy-8-methyl-N-p-tolysulfonyl-2,3,4,4a,9,9a-hexahydro-1H-carbazol-1-one.     

Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-sulfonyl derivatives of 1,4-benzoquinone monoimine with substituted hydrazines

Reaction direction of N-sulfonyl derivatives of 1,4-benzoquinone monoimine with substituted hydrazines depends on the redox potential of the quinone imine and on the basicity of the hydrazine. Aryl (alkyl)hydrazines of high basicity favor the reduction of quinone monoimine. In reactions with less basic aroylhydrazones N'-(4-oxocyclohexa-2,5-dienylidene)aroylhydrazides were obtained only from the alkylsubstituted in the quinoid ring N-sulfonyl derivatives possessing a lower redox potential.     

<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.     

Chemoselective acylation of monosubstituted thiacalix[4]arene with di-<Emphasis Type="Italic">tert</Emphasis>-butyl dicarbonate

Mono-, di-, and tetrasubstituted derivatives of p-tert-butylthiacalix[4]arene containing tert-butylcarbamate, tert-butylcarbonate, and tert-butyl fragments have been prepared for the first time. Depending on the reaction conditions (reagents ratio, temperature, and the presence of a base), the interaction of the monoamine derivative of p-tert-butylthiacalix[4]arene with di-tert-butyl dicarbonate can lead to the formation of mono-, di-, and tetrasubstituted products.     

3,5-Di-<Emphasis Type="Italic">tert</Emphasis>-butyl-1,2-benzoquinone in the synthesis of quinolino[4,5-<Emphasis Type="Italic">bc</Emphasis>][1,5]benzoxazepines,aminophenols, and phenoxazines

Reaction of 3,5-di-tert-butyl-1,2-benzoquinone with 5-amino-4-chloroquinolines gave derivatives of a new fused heterocyclic system, substituted quinolino[4,5-bc][1,5]benzoxazepines. The molecular structure of 9,11-di-tert-butyl-2,4,6-trimethyl-7H-quinolino[4,5-bc][1,5]benzoxazepine was determined by X-ray analysis. 3,5-Di-tert-butyl-1,2-benzoquinone reacted with o-nitro-, o-acyl-, and o-methoxycarbonylanilines and some amino-substituted nitrogen-containing heterocycles to form the corresponding sterically hindered N-aryl-(hetaryl)-o-aminophenols. Di-tert-butyl-substituted phenoxazines were obtained as a result of thermal cyclization of intermediately formed quinone imines.     

Synthesis and membrane-protective activity of 2,6-diisobornylphenol derivatives with <Emphasis Type="Italic">N</Emphasis>- and <Emphasis Type="Italic">O</Emphasis>-containing fragments at position 4

Two series of new amide derivatives containing 2,6-diisobornylphenol moiety were synthesized based on 3,5-diisobornyl-4-hydroxybenzoic acid and 4-butylaminomethyl-2,6-diisobornylphenol. Toxicity, membrane-protective (MP) and antioxidant (AO) activity of the obtained compounds were evaluated using red blood cells of laboratory mice as the test object. The tests demonstrated the absence of hemolytic activity for all the synthesized derivatives and the presence of high MP and AO activity under conditions of acute H₂O₂-induced oxidative stress for (3,5-diisobornyl-4-hydroxyphenyl)(morpholino)methanone and N-n-butyl-N-(3,5-diisobornyl-4-hydroxybenzyl)acetamide. A comparison of the data of the newly obtained compounds and those of described earlier 2,6-diisobornylphenol derivatives with N- and O-containing fragments at position 4 (alkoxymethyl, carboxy, and aminomethyl derivatives) led to a conclusion that the most promising for further studies of pharmacological activity are compounds containing methoxycarbonyl, methoxymethyl, ethoxymethyl, morpholinomethyl, di-n-butylaminomethyl, (azepan-1-yl)methyl, or N-acetyl-N-alkylaminomethyl function, which provide low toxicity and high MP and AO activity.     

Cyclizations of monocyclic 5-nitropyridin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

Reactions of 5-nitropyridin-2(1H)-one and its N-methyl derivative with hydrazine hydrate led to the formation of (1H-pyrazol-3-yl) acetohydrazide. Under analogous conditions, 1,3-dimethyl-5-nitropyridin2(1H)-one gave rise to 2-(1H-pyrazol-3-yl)propionohydrazide, while 6-methyl-5-nitropyridin-2(1H)-one was converted into (5-methyl-1H-pyrazol-3-yl)acetohydrazide. Hydrazinolysis of 4-methyl-5-nitropyridin-2(1H)-one resulted in the formation of 3-methyl-4-nitro-1H-pyrazole. The mechanism of recyclization of nitropyridine derivatives by the action of hydrazine hydrate was studied using 5-nitropyridin-2(1H)-one and 1-methyl-5-nitropyridin-2(1H)-one as examples.     

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.     

Reaction of anthranilic acid 2-<Emphasis Type="Italic">N</Emphasis>-phenylhydrazide with cyclic anhydrides

In the reaction with cyclic anhydrides the anthranilic acid 2-N-phenylhydrazide depending on conditions yielded either anthranilic acid 2-N-acyl-2-N′-phenylhydrazides, 2-R-3-anilinoquinazolin-4(3H)-ones, or derivatives of 1-phenylpyridazino[3,2-b]quinazoline-2,10-dione.