Homo and hetero glaser coupling involving acetylene derivatives of trifluoromethanesulfonamide

Glaser homocoupling of N,N-bispropargyltriflamide led to the formation of N,N'-hexa-2,4-diyne-1,6-diylbis(N-prop-2-yne-1-triflamide). Further condensation into a 14-membered heterocycle, 1,8-bis-(triflyl)-1,8-diazacyclotetradeca-3,5,10,12-tetrayne did not occur evidently because of rigid steric requirements to the cyclization. In the Glaser heterocoupling of N-propargyltriflamide with arylacetylenes ArC≡CH (Ar = Ph, p-CNC₆H₄) the condensation products formed in 20–30% yields.     

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.     

<Emphasis Type="Italic">N</Emphasis>-allyl and <Emphasis Type="Italic">N</Emphasis>-propargyl trifluoromethanesulfonimides. Theoretical analysis

Tautomers of N-allyl- and N-propargyl-substituted trifluoromethanesulfonimides (CF₃SO₂)₂NR (R = CH₂CH=CH₂, Z/E-CH=CHMe, CH₂C≡CH, CH=CH=CH₂, C≡CCH₂) were calculated by the DFT (B3LYP, wB97XD, PBE1PBE), MP2, and CBS-QB3 methods. The results were compared with the theoretical data for the corresponding amines and amides NHRR¹ (R¹ = H, CF₃SO₂). It was shown that there is no conjugation between the nitrogen atom and C=C bond and that conjugation exists with the C≡C bond with electron density displacement toward the nitrogen atom. The calculations of anions derived from N-allyl- and N-propargyl-trifluoromethanesulfonimides revealed the possibility of their rearrangement with elimination of trifluoromethanesulfinate anion and formation of its H-complex with N-(prop-2-en-1-ylidene)trifluoromethanesulfonamide or N-(prop-2-yn-1-ylidene)trifluoromethanesulfonamide.     

Cyclization of trifluoro-<Emphasis Type="Italic">N</Emphasis>-(prop-2-yn-1-yl)methanesulfonamides to <Emphasis Type="Italic">N</Emphasis>-(hydroxymethyl)-1,2,3-triazoles

Three-component heterocyclizations of trifluoro-N-(prop-2-yn-1-yl)methanesulfonamide, trifluoro-N-pheny-N-(prop-2-yn-1-yl)methanesulfonamide, and trifluoro-N,N-di(prop-2-yn-1-yl)methanesulfonamide with formaldehyde and sodium azide afforded N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-, N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-N-phenyl-, and N,N-bis{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}trifluoromethanesulfonamides as the major products together with minor 1-(hydroxymethyl)-1H-1,2,3-triazole isomers.     

3-(1-Methyl-1-nitroethyl-1-<Emphasis Type="Italic">ONN</Emphasis>-azoxy)-4-aminofuroxan. Synthesis and transformations of the amino group

A four-step procedure to convert 4-(1-methyl-1-nitroethyl-1-ONN-azoxy)-3-cyanofuroxan into 3-(1-methyl-1-nitroethyl-1-ONN-azoxy)-4-aminofuroxan was developed. The pathways of transformation of the amino group of the synthesized compound into N-nitramino-, N-alkyl-N-nitramino-, N,N’-methylenediamino-, N,N’-methylene-N,N’-dinitramino-, and azo groups were studied.     

Design,synthesis and anti-mycobacterial evaluation of some new <Emphasis Type="Italic">N</Emphasis>-phenylpyrazine-2-carboxamides

N-Phenylpyrazine-2-carboxamides (anilides of pyrazinoic acids with simple substituents in various positions) were previously shown to possess significant biological activities in vitro, markedly anti-mycobacterial and photosynthesis-inhibiting activity. Based on structure-activity relationships (SAR) extracted from previously published series, 25 new anilides of non-substituted pyrazinoic acid (POA), 5-CH₃-POA, 6-Cl-POA, 5-tert-butyl-POA and 5-tert-butyl-6-Cl-POA were designed and synthesised. The phenyl part was substituted with simple hydrophobic substituents chosen from methyl and halogens. 5-tert-Butyl-N-(5-fluoro-2-methylphenyl)pyrazine-2-carboxamide (9), N-(3-chloro-4-methylphenyl)-5-methylpyrazine-2-carboxamide (12), 6-chloro-N-(3-chloro-4-methylphenyl)pyrazine-2-carboxamide (13) and 6-chloro-N-(5-iodo-2-methylphenyl)pyrazine-2-carboxamide (18) possessed whole cell anti-mycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of around 10 μM. Importantly, no cytotoxicity in the HepG2 model was detected in vitro at the concentrations tested and the estimated IC50 values were in hundreds of μM, indicating promising selectivity. N-(3-Chloro-4-methylphenyl)pyrazine-2-carboxamide (11) and N-(4-chloro-2-iodophenyl)pyrazine-2-carboxamide (21) exerted significant activity against Mycobacterium kansasii with MIC 12.6 μM and 8.7 μM, respectively. No activity was detected against Mycobacterium avium. SAR were in accordance with those observed for the derivatives previously published.     

Synthesis of Dicarboxylic Acid Amides and Diamides on the Basis of [4-(4-Methoxyphenyl)tetrahydro-2<Emphasis Type="Italic">H</Emphasis>-pyran-4-yl]methanamine

The condensation of various nonaromatic amines with ethyl N-{[4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methyl}oxamate prepared from [4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methanamine and diethyl oxalate afforded the corresponding N,N'-disubstituted oxamides. N-Aryloxamides were synthesized by the reaction of [4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methanamine with ethyl N-aryloxamates. The condensation of N-{[4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methyl}succinamic acid with primary amines gave N,N'-disubstituted siccinamides.     

Thermooxidative decomposition of heterocyclic <Emphasis Type="Italic">N</Emphasis>-oxides

Thermooxidative decomposition of pyridine N-oxide, 4-(4-dimethylaminostyryl)pyridine N-oxide, 4-(4-methoxystyryl)pyridine N-oxide, quinoline N-oxide, 2-methylquinoline N-oxide, 4-chloroquinoline N-oxide, 2-styrylquinoline N-oxide, and 2-(4-dimethylaminostyryl)quinoline N-oxide was studied. The kinetic parameters of the thermooxidative processes were calculated according to three independent procedures. The relation between the nature of heterocyclic N-oxide and its stability to thermal oxidation was analyzed.     

Azanorbornenes in radical polymerization reactions

Activity of azanorbornenes: N-benzyl-2-azanorborn-5-ene, (2-azanorborn-5-en-2-yl)methyl acetate, and N-allyl-2-azanorborn-5-ene in radical homo-and copolymerization with vinyl monomers and sulfur dioxide was studied.     

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.     

Reactions of arylsulfinyl chlorides and <Emphasis Type="Italic">N</Emphasis>-(arylsulfonyl)arylsulfinimidoyl chlorides with <Emphasis Type="Italic">p</Emphasis>-aminophenols

In reactions of arylsulfinyl chlorides and N-(arylsulfonyl)arylsulfinimidoyl chlorides with p-aminophenols formed N-arylthio-1,4-benzoquinone imines, evidently through a stage of N-arylsulfinyl-4-aminophenols and N-(N-arylsulfonyl)arylsulfinylimidoyl-4-aminophenols that under the reaction conditions eliminate respectively H₂O and ArSO₂NH₂.     

Synthesis of corn rootworm pheromones from commercial diols

A mixture of stereoisomers of the corn rootworm pheromones was synthesised via the Grignard coupling of protected bromohydrins with alkylcuprate as a key step. The synthesis of 8-methyldec-2-yl propanoate (I), the northern corn rootworm Diabrotica longicornis Say pheromone, was achieved from pentane-1,5-diol in four steps with an overall yield of 35.1 % and 10-methyltridecan-2-one (II), the southern corn rootworm Diabrotica undecimpunctata howardi Barber pheromone, was synthesised from octane-1,8-diol as commercially available starting material in five steps with an overall yield of 28.7 %.     

Synthesis of New Cyclopenta[<Emphasis Type="Italic">b</Emphasis>]quinoline Derivatives

A series of new 11-(R-phenyl)-8,9-dihydro-7H-benzo[f]cyclopenta[b]quinolin-10(11H)-ones and 7,14-bis(R-phenyl)-2,3,9,10,11,14-hexahydrocyclopenta[2,3]quinolino[8,7-h]cyclopenta[b]quinoline-1,8(4H,7H)-diones were synthesized by three-component condensation of naphthalen-2-amine or naphthalene- 1,5-diamine with substituted benzaldehydes and cyclopentane-1,3-dione in one step through intermediate formation of unstable arylaminoketoenol.     

Electrophilic cyclization of <Emphasis Type="Italic">N</Emphasis>-allyl(propargyl)-5-amino-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-4-carboxamides. Synthesis of 4-[(dihydro)oxazol-2-yl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-5-amines

N-Allyl-5-amino-1H-pyrazole-4-carboxamides in reactions with polyphosphoric acid, with N-halosuccinimides in chloroform, and with (chlorosulfanyl)benzenes in nitromethane in the presence of lithium perchlorate underwent cyclization involving the N-allylamide fragment to give 4-[5-methyl(halomethyl)-4,5-dihydrooxazol-2-yl]-1H-pyrazol-5-amines and 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methyl]-4,5-dihydro-1,3-oxazolium perchlorates, respectively. Analogous reactions of N-propargyl-5-amino-1H-pyrazole-4-carboxamides with polyphosphoric acid afforded 4-(5-methyloxazol-2-yl)-1H-pyrazol-5-amines, and with (chlorosulfanyl) benzenes, 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methylidene]-4,5-dihydro-1,3-oxazolium perchlorates.     

Reactions of 1,3-Dialkyl-5-amino-1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-ones with acetylacetone and ethyl acetoacetate

1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones reacted with acetylacetone to give the corresponding 4-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)pent-3-en-2-ones which underwent intramolecular cyclization to 1,3-dialkyl-5,7-dimethyl-1,3-dihydro-2H-imidazo[4,5-b]-[1,8]naphthyridin-2-ones on heating in polyphosphoric acid or diphenyl ether. Analogous reaction of 1,3-dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones with ethyl acetoacetate led to the formation of ethyl 3-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)but-2-enoates whose cyclization afforded 1,3-dialkyl-8-hydroxy-7-methyl-1,3-dihydro-2H-imidazo[5,4-b][1,8]naphthyridin-2-ones.     

3-(4-fluorophenyl)-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-4-carbaldehyde in the synthesis of aza-and diazaphenanthrene derivatives

Condensation of 3-(4-fluorophenyl)-1H-pyrazole-4-carbaldehyde with 2-naphthyl-or 6-quinolylamine and CH-acids (acetone, acetophenone, cyclic mono-and β-diketones) provided new derivatives of benzo[f]quinoline, benzo[a]phenanthridine, benzo[a]acridine, and 4,7-phenanthroline. The arising in the course of the reaction [3-(4-fluorophenyl)-1H-pyrazole-4-ylmethylene]-2-naphthyl-(or 6-quinolyl)amines, [3-(4-fluorophenyl)-1H-pyrazole-4-ylmethylene]-1,3-indandione, and octahydro-1,8-xanthenedione derivatives were isolated.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-(Polychloroethylidene)arene-and - trifluoromethanesulfonamides with indoles

N-(Polychloroethylidene)arene-and -trifluoromethanesulfonamides reacted with indole and N-substituted indoles to give the corresponding N-[2,2-dichloro(or 2,2,2-trichloro)-1-(1H-indol-3-yl)ethyl]-substituted sulfonamides. Unlike N-(2,2,2-trichloroethylidene)trifluoromethanesulfonamide, less electrophilic N-(poly-chloroethylidene)arenesulfonamides failed to react with 1-(4-nitrophenyl)-1H-indole. Previously unknown N,N’-bis(2,2-dichloroethylidene)biphenyl-4,4’-disulfonamide reacted with 1-benzyl-1H-indole at both azomethine fragments. Likewise, reactions of 1,6-bis(1H-indol-1-yl)hexane and 1,4-bis(1H-indol-1-ylmethyl)-benzene with N-sulfonyl trichloroacetaldehyde imines involved both indole rings in the former.     

<Emphasis Type="Italic">N</Emphasis>-(4-methoxy-3-nitrobenzyl) derivatives of some nitrogen-containing heterocycles

A number of nitrogen heterocycles reacted with 4-methoxy-3-nitrobenzyl chloride in dimethyl-formamide in the presence of potassium carbonate to give the corresponding N-(4-methoxy-3-nitrobenzyl) derivatives. The reaction of 5-fluoro-1,3-bis(4-methoxy-3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione with aqueous methylamine afforded N,N′-bis(4-methylamino-3-nitrobenzyl)urea, whereas analogous reaction with 1-(4-methoxy-3-nitrobenzyl)-2-(methylsulfanyl)-1H-benzimidazole resulted in substitution of the methoxy group by methylamino.     

Synthesis and transformations of 3-allyl-7,10-dimethyl-2-sulfanylidene-2,3,5,6-tetrahydrospiro[benzo[<Emphasis Type="Italic">h</Emphasis>]quinazoline-5,1′-cyclopentan]-4(1<Emphasis Type="Italic">H</Emphasis>)-one

Ethyl 4′-amino-5′,8′-dimethyl-1′H-spiro[cyclopentane-1,2′-naphthalene]-3′-carboxylate reacted with allyl isothiocyanate to give 3-allyl-7,10-dimethyl-2-sulfanylidene-2,3,5,6-tetrahydrospiro[benzo[h]quinazoline- 5,1′-cyclopentan]-4(1H)-one. Reactions of the latter with alkyl halides and hydrazine hydrate and subsequent transformations of the products afforded a series of new benzo[h]quinazoline derivatives containing an allyl group in the 3-position.     

New green fluorescent polymer sensors for metal cations and protons

A new 4-(N-methylpiperazine)-N-allyl-1,8-naphthalimide with intense yellow-green fluorescence has been synthesized. Then it has been copolymerized with styrene and methylmetacrylate. The photophysical characteristics of the fluorescent dye and its copolymers (poly(St-co-NI) and poly(MAA-co-NI)) have been determined viewing their sensor properties for protons and transition metal cations (Cu²⁺, Fe³⁺ and Zn²⁺). Fluorescence enhancement is the photophysical response of the 4-(N-methylpiperazine)-N-allyl-1,8-naphthalimide to the presence of metal cations and protons, while fluorescence quenching is observed for both copolymers.