Structure and Reactivity of Bicyclo[2.2.1]hept-2-ene-<Emphasis Type="Italic">endo</Emphasis>-5,<Emphasis Type="Italic">endo</Emphasis>-6-dicarboxylic (endic) Acid Hydrazide

Establishing of the structure of hydrazinolysis product obtained from bicyclo[2.2.1]hept-2-ene-endo-5, endo-6-dicarboxylic (endic) acid was performed by preparation of the compound under alternative conditions followed by comparison of the characteristics and spectral parameters of the resulting substances, and also by quantum-chemical calculations by the density functional method of the chemical shifts in ¹H and ¹³C NMR spectra of different reaction products. The X-ray diffraction analysis of the hydrazide was also carried out. The compound obtained was assigned a structure of N-aminobicyclo[2.2.1] hept-2-ene-endo-5,endo-6-dicarboximide. The products were prepared by its reactions with arylsulfonyl chlorides, benzoyl chlorides, m-tolyl and p-toluene-sulfonyl isocyanates, phenyl isothiocyanate, with o-nitrobenzaldehyde, and oxiranes (1,2-epoxycyclohexane and 2,3-epoxypropylcarbazole). The aromatic sulfonamides, carboxamides, and ureas were epoxidized by performic acid obtained in situ from the formic acid and hydrogen peroxide. Products of [3+2]-cycloaddition of aryl azides to the strained double bond in the N-aminobicyclo[2.2.1] hept-2-ene-endo-5,endo-6-dicarboximide and its derivatives. The structures of compounds obtained were confirmed by their IR, 1H and 13C NMR spectra.     

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.     

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 of fluoroquinoxalin-2(1<Emphasis Type="Italic">H</Emphasis>)-one derivatives containing substituents in the pyrazine and benzene fragments

6,7-Difluoroquinoxalin-2-one reacted with indoles, 5,5-dimethylcyclohexane-1,3-dione, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, resorcinol, and pyrogallol on heating in acetic acid to give products of hydrogen substitution in the heterocyclic fragment. Heating of 6,7-difluoro-3-(1H-indol-3-yl)quinoxalin-2(1H)-ones with N-methylpiperazine gave the corresponding 7-(4-methylpiperazin-1-yl) derivatives.     

Nitration of 3-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2-diazaphenalene and its n-substituted derivatives

1-Substituted 1H-1,2-diazaphenalenes (1H-benzo[de]cinnolines) undergo nitration with nitric acid leading to the formation of di- and trinitro derivatives. The yield of nitration products depends on nitric acid concentration.     

<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.     

Thebaine Adducts with Maleimides. Synthesis and Transformations

Diels-Alder reaction of thebaine with maleimides is structurally specific and yields [7,8,3′,4′ ]-succinimido-endo-ethenotetrahydrothebaines containing N′-alkyl, cycloalkyl, aralkyl or aryl substituents. N′-[1(S)-hydroxymethyl-2-methylpropyl]-succinimido-6,14-endo-ethenotetrahydrothebaine formed in reaction of S-valinol with (7α,8α)-anhydrido-6,14-endo-ethenotetrahydrothebaine. The reduction of the adducts by LiAlH₄ afforded N′-substituted 7,8-pyrrolidino-endo-ethenotetrahydrothebaines. The reduction of fused succinimides by NaBH₄ resulted in the corresponding 2′α-hydroxylactam derivatives. O-Demethylation of the tetrahydrothebaine pyrrolidine derivatives effected by BBr₃ afforded compounds of the tetrahydrooripavine series. The O-demethylation of tetrahydrothebaine succinimide derivatives gave rise to the corresponding 6-demethyl-endo-ethenotetrahydrooripavines. Alkylation conditions were found for N′-(4-hydroxyphenethyl)-substituted tetrahydrothebaine succinimide derivatives.     

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.     

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.     

Polyfunctional imidazoles: XIV. 4-sulfonyl-5-formyl-1<Emphasis Type="Italic">H</Emphasis>-imidazoles

Oxidative chlorination of 1-aryl-4-benzylsulfanyl-1H-imidazole-5-carbaldehydes gave 1-aryl-5-formyl-1H-imidazole-4-sulfonyl chlorides which reacted with secondary amines and phenols to produce the corresponding N,N-disubstituted 5-formylimidazole-4-sulfonamides and aryl sulfonates. The reaction of 1-aryl-5-formyl-1H-imidazole-4-sulfonyl chlorides with sodium azide, followed by reduction of the resulting sulfonyl azides, led to the formation of N-unsubstituted 5-formylimidazole-4-sulfonamides, and the reaction with alcohols, to 5-formylimidazole-4-sulfonic acids.     

Sc(OTf)<Subscript>3</Subscript> catalyzed synthesis of novel 6-phenyl-6<Emphasis Type="Italic">H</Emphasis>-chromeno[4,3-b]quinolines and evaluation of their cytotoxicity

Novel 6-phenyl-6H-chromeno[4,3-b]quinoline derivatives have been prepared by reaction of 4-chloro-2-phenyl-2H-chromene-3-carbaldehyde with various aromatic amines using 5 mol % of Sc(OTf)3 in acetonitile. This is the first example of one-pot synthesis of 6-phenyl-6H-chromeno[4,3-b]quinoline from 4-chloro-2-phenyl-2H-chromene-3-carbaldehyde at ambient temperature. Preliminary evaluation of cytotoxic activity of these chromeno[4,3-b]quinoline derivatives has been carried out. Some products exhibited anti cancer activity against two carcinoma cell lines A549 and B-16.     

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.     

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.     

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.     

Polymerization of methyl methacrylate in the presence of <Emphasis Type="Italic">o</Emphasis>-iminoquinones: Reversible and irreversible inhibition

New regulators of radical polymerization of methyl methacrylate based on N-(aryl)-o-iminoquinones of various structures are proposed. It is shown that samples of polymethylmethacrylate with the participation of N-(aryl)-o-iminobenzoquinones could be used as macroinitiators of polymerization. Optimal conditions to synthesize polymers in the presence of o-iminobenzoquinones are determined, which make it possible to obtain polymethylmethacrylate with a polydispersity coefficient of no more than 1.5 on deep conversions during bulk polymerization.     

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.     

Synthesis of new aryl(hetaryl)vinyl-substituted benzo[<Emphasis Type="Italic">f</Emphasis>]quinolines and 4,7-phenanthrolines

Previously unknown 1-[2-aryl(quinolin-2-yl)ethenyl]-3-[aryl(quinolin-2-yl)]benzo[f]quinolines and 3-aryl-1-(2-arylethenyl)-4,7-phenanthrolines were synthesized by reactions of 1-methylbenzo[f]quinolines and 1-methyl-4,7-phenanthrolines with substituted N-benzylideneanilines and N-(quinolin-2-ylmethylidene)aniline on heating in dimethylformamide in the presence of potassium hydroxide.     

Novel route of the reaction of trifluoromethyl-containing N-methyl(4-ethoxyphenyl)imidazolidin-2-ones with urea

The reactions of perfluorobiacetyl with N-(4-ethoxyphenyl)- and N-methylurea afforded cis- and trans-isomers of 1-methyl-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-one and 1-(4-ethoxyphenyl)-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-one in a yield of ～60—75%. N-Alkyl(aryl)bis(trifluoromethyl)imidazooxazoles were obtained as unexpected products in the reaction of 1-alkyl(aryl)-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-ones with urea in dimethylacetamide. The reaction is accompanied by the rearrangement of imidazolidin-2-ones to N-alkyl(aryl)-5,5-bis(trifluoromethyl)hydantoins with CF₃ group migration from position 5 to position 4 of the starting heterocycle. A similar rearrangement is observed on boiling of the studied imidazolidin-2-ones in dimethylacetamide. The molecular structures of 3-(4-ethoxyphenyl)-5,5-bis(trifluoromethyl)imidazolidine-2,4-dione and 6-(4-ethoxyphenyl)-3a,6a-bis(trifluoromethyl)tetrahydroimidazo[4,5-d]oxazole-2,5-dione were studied by X-ray diffraction analysis.     

Cyclocondensation of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 2-aminoimidazole and 2-aminobenzimidazole

Cyclization of N-aryl-3-oxobutanethioamides with 2-aminoimidazole and 2-aminobenzimidazole gave 7-methyl-5,8-dihydroimidazo[1,2-a]pyrimidine-5-thione or 2-methylpyrimido[1,2-a]benzimidazole-4(1H)-thione and 4-(arylamino)-2-methylpyrimido[1,2-a]benzimidazoles whose ratio depends on the nature of aryl substituents in the initial butanethioamides and on the presence of a protic solvent.     

Reactions of trifluoromethanesulfonamide with amides and paraformaldehyde

Two- and three-component condensations of paraformaldehyde with trifluoromethanesulfonamide, acetamide, trifluoroacetamide, 1H-benzotriazole, methanesulfonamide, and malonamide were studied. N-Hydroxymethyl derivatives of trifluoroacetamide and 1H-benzotriazole reacted with trifluoromethanesulfonamide to give N-(trifluoroacetylaminomethyl)- and N-(1H-benzotriazol-1-ylmethyl)-substituted derivatives of tri-fluoromethanesulfonamide, as well as N,N′-methylenebis(trifluoromethylsulfonamide) and N-(trifluoromethyl-sulfonylaminomethyl)trifluoroacetamide as transamination products. Three-component condensation of trifluoromethanesulfonamide with paraformaldehyde and methanesulfonamide led to the formation of 1-methylsulfonyl-3,5-bis(trifluoromethylsulfonyl)hexahydro-1,3,5-triazine, and the reaction of trifluoromethanesulfonamide with paraformaldehyde and malonamide gave 4,10-bis(trifluoromethylsulfonyl)-2,4,8,10-tetraazaspiro-[5.5]undecane-1,7-dione whose structure was proved by X-ray analysis.