Synthesis and reactions of 3-(3-ethoxycarbonyl-1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)propenic acid

The reaction of ethyl 4-formyl-1-phenyl-1H-pyrazole-3-carboxylate with the malonic acid led to the formation (2E)-3-(3-ethoxycarbonyl-1-phenyl-1H-pyrazol-4-yl)propenic acid. In reactions of this acid chloride with 4-amino-5-aryl(hetaryl)-4H-1,2,4-triazole-3-thiols were obtained ethyl 4-[(E)-2-{3-aryl(hetaryl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl}ethenyl]-1-phenyl-1H-pyrazoe-3-carboxylates, with 5-aryltetrazoles, ethyl 4-[(E)-2-(5-aryl-1,3,4-oxadiazol-2-yl)-ethenyl]-1-phenyl-1H-pyrazole-3-carboxylates, with 1-(2-hydroxy-3,5-dimethylphenyl) followed by the Baker-Venkataraman rearrangement and the cyclization, ethyl 4-[(E)-2-(6,8-dimethyl-4-oxo-4Hchromen-2-yl)ethenyl]-1-phenyl-1H-pyrazole-3-carboxylate.     

Synthesis and antimicrobial activity of some acridone derivatives bearing 1,3,4-oxadiazole moiety

Novel acridone derivatives bearing 1,3,4-moiety were synthesized by intramolecular cyclization of N´-[2-(9-oxoacridin-10(9H)-yl)acetyl]arylhydrazides. Study of antimicrobial activity of the synthesized compounds reveals that some of them are more active than the comparator drug rivanol.     

Crystal structure of 9-(5,5-dimethyl-2,4,5,6-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-phenalen-2-yl)-5,5,9-trimethyl-5,6,8,9-tetrahydrocyclopenta[<Emphasis Type="Italic">a</Emphasis>]phenalen-10(4<Emphasis Type="Italic">H</Emphasis>)-one

The structure of 9-(5,5-dimethyl-2,4,5,6-tetrahydro-1H-phenalen-2-yl)-5,5,9-trimethyl-5,6,8,9-tetrahydrocyclopenta[а]phenalen-10(4H)-one was determined by X-ray crystallography. The intermolecular interaction energies were calculated by the atom-atomic approach for the crystal structure. The character of the crystal structure and the structural subclass were established.     

Quantum chemical studies of azoles 3. Thermodynamic stabilities of neutral molecules and intermediates formed in electrophilic substitution of azoles containing three or four heteroatoms

Density functional theory quantum chemical calculations of thermodynamic stabilities in the gas phase and in water were carried out for 1,3,4-oxadiazole and 1,3,4-thiadiazole, 1,2,4-1H-triazole and 1,2,4-4H-triazole, 1,2,3,4-1H-tetrazole and 1,2,3,4-2H-tetrazole molecules, and for cationic and bipolar (carbenoid) intermediates formed by these molecules in electrophilic substitution reactions (with proton as model electrophile) and the results obtained are compared. Differences in the chemical behavior of pairs of isomeric 1H- and 4H-1,2,4-triazoles and 1H- and 2H-tetrazoles are analyzed.     

Synthesis,Structure, and Anti-influenza Activity of 2-(Adamantan-1-yl)-5-aryl-1,3,4-oxadiazoles and 2-(Adamantan-1-yl)-5-aryltetrazoles

Two series of new adamantyl derivatives of polynitrogen heterocycles, 2-(adamantan-1-yl)-5-aryl- 1,3,4-oxadiazoles and 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles, have been synthesized, and their structure has been determined by NMR spectroscopy, mass spectrometry, and X-ray analysis. Biological studies in vitro have revealed high inhibitory activity of some of the synthesized 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles against H1N1 influenza A viruses in combination with a relatively low selectivity.     

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 1,2,4- and 1,3,4-oxadiazoles from 1-aryl-5-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-4-carbonyl chlorides

5-Substituted 2-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazoles were synthesized by reaction of 1-aryl-5-methyl-1H-1,2,3-triazole-4-carbonyl chlorides with the corresponding 5-substituted 1H-tetrazoles. 5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl chloride reacted with N′-hydroxybenzimidamides to give 3-aryl-5-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazoles. Reactions of 4-(5-methyl-1H-1,2,3-triazol-1-yl)benzoic acid with N′-hydroxybenzimidamides resulted in the formation of 3-aryl-5-[4-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl]-1,2,4-oxadiazoles.     

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.     

Synthesis of heterocycles based on arylation products of unsaturated compounds: XVII. Arylation of 2-acetylfuran and synthesis of 3-R-6-(5-aryl-2-furyl)-7<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazines

Reaction of 2-acetylfuran with arenediazonium chlorides under Meerwein reaction conditions led to the formation of 5-aryl-2-acetylfurans. The bromination of these compounds gave 2-bromo-1-(5-aryl-2-furyl)-ethanones that reacted with 4-amino-4H-5-R-1,2,4-triazole-3-thiols to form 3-R-6-(5-aryl-2-furyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines.     

Functionalization of methyl 3-acetyl-5-[(methoxycarbonyl)amino]-2-methyl-1<Emphasis Type="Italic">H</Emphasis>-indole-1-carboxylate

Oxidative heterocyclization of methyl 3-{1-[2-(carbamoylhydrazinylidene)]ethyl}-2-methyl-5-[(methoxycarbonyl)amino]-1H-indole-1-carboxylate by the action of selenium dioxide in acetic acid and heating of the corresponding thiosemicarbazone in boiling acetic anhydride gave 1,2,3-selenadiazole and 2,3-dihydro-1,3,4-thiadiazole derivatives, respectively. Methyl 3-acetyl-2-methyl-5-[(methoxycarbonyl)amino]-1H-indole-1-carboxylate reacted with selenium dioxide in dioxane–water (30: 1) at 80?90°C to form methyl 5-[(methoxycarbonyl)amino]-2-methyl-3-(2-oxoacetyl)-1H-indole-1-carboxylate whose condensation with o-phenylenediamine afforded methyl 2-methyl-5-[(methoxycarbonyl)amino]-3-(quinoxalin-2-yl)-1H-indole-1-carboxylate.     

Fused pyrimidine systems: XVI. Electrophilic intramolecular cyclization of 2-(alkenylsulfanyl)pteridin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

2-[Allyl(but-3-en-1-yl, pent-4-en-1-yl)sulfanyl]pteridin-4(3Н)-ones at heating in polyphosphoric acid undergo an intramolecular cyclization affording respectively 9-methyl-8,9-dihydro-5H-[1,3]thiazolo[3,2-a] pteridin-5-one and 10-methyl(ethyl)-9,10-dihydro-5Н,8Н-[1,3]thiazino[3,2-a]pteridin-5-ones of angular structure. The cyclization of 2-(alkenylsulfanyl)pteridin-4(3Н)-ones under the action of iodine or arylsulfenyl chlorides afforded iodo(arylsulfanyl) derivatives of angularly fuzed thiazolo- and thiazinopteridines.     

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.     

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.     

Synthesis of 2-(halomethyl)-3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>-pyrido[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]oxazinium halides

Alkylation of pyridin-2(1H)-one and 5-nitropyridin-2(1H)-one with 4-bromobut-1-ene afforded a mixture of N- and O-butenyl derivatives. 1-(But-3-en-1yl)pyridin-2(1H)-one and 1-(but-3-en-1-yl)-5-nitropyridin- 2(1H)-one reacted with bromine and iodine to give 2-(halomethyl)-3,4-dihydro-2H-pyrido[2,1-b][1,3]-oxazinium halides.     

Synthesis of nitrogen-containing heterocycles on the basis of 3-(4-acetylphenyl)-1-methylquinolin-2(1<Emphasis Type="Italic">H</Emphasis>)-one

The Meerwein reaction of 1-methylquinolin-2(1H)-one with 4-acetylbenzenediazonium chloride gave 3-(4-acetylphenyl)-1-methylquinolin-2(1H)-one which was brominated to 3-[4-(2-bromoacetyl)phenyl]-1-methylquinolin-2(1H)-one. The latter reacted with pyridine, 4-methylpyridine, quinoline, benzo[f]quinoline, and triphenylphosphine to afford the corresponding quaternary salts, and its reactions with thioacetamide, thiourea, 2-aminopyridine, and 2-aminopyrimidine led to the corresponding thiazole, imidazo[1,2-a]pyridine, and imidazo[1,2-a]pyrimidine derivatives containing a 2-oxoquinoline fragment. 3-(4-{2-[2-(Arylmethylidene)-hydrazinyl]-1,3-thiazol-4-yl}phenyl)-1-methylquinolin-2(1H)-ones were obtained by condensation of 3-[4-(2-bromoacetyl)phenyl]-1-methylquinolin-2(1H)-one with thiosemicarbazide and aromatic aldehydes.     

Some Transformations of 2-(Chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[<Emphasis Type="Italic">h</Emphasis>]quinazolin-4(3<Emphasis Type="Italic">H</Emphasis>)-one

The condensation of 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-carbonitrile with chloroacetyl chloride afforded chloro-N-(2-cyano-3,3-dimethyl-3,4-dihydronaphthalen-1-yl)acetamide which underwent cyclization to 2-(chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin-4(3H)-one. The latter reacted with various nucleophiles (alkali metal alkoxides, piperazine, 2-sulfanylethanol) to give 2-(alkoxymethyl)-, 2-(piperazin-1-ylmethyl)-, and 2-{[(2-hydroxyethyl)sulfanyl]methyl}-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin- 4(3H)-ones. The condensation of 2-(chloromethyl)benzo[h]quinazoline with 2-thioxo derivatives of quinazoline and benzo[h]quinazolines led to the formation of bis-quinazolines in which 5,5-dimethyl-5,6- dihydrobenzo[h]quinazolin-4(3H)-one fragment is linked to quinazoline or benzo[h]quinazoline system through a CH₂S bridge.     

Synthesis and antioxidant evaluation of some new 2-benzoylamino-5-hetaryl-1,3,4-oxadiazoles

A series of new functionalized 2-benzoylamino-5-hetaryl-1,3,4-oxadiazoles were efficiently synthesized via the reaction of the versatile key intermediates, 2-benzoylamino-5-cyanomethyl-1,3,4-oxadiazole (1) and N-(5-(5-amino-3-phenylamino)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)-benzamide (13), with some appropriate electrophilic reagents. The structures of the newly synthesized compounds were established on the basis of elemental analyses, spectral data, and by alternative synthesis wherever possible. The mechanisms of the studied reactions are discussed. Also, we evaluate the antioxidant activity of some representative examples of the newly prepared compounds. Among the synthesized compounds, 2-benzoylamino-5-cyanomethyl-1,3,4-oxadiazole (1) and N-(5-(7-methyl-5-oxo-2-(phenylamino)-4,5-dihydropyrazolo[1,5-a]pyrimidin-3-yl)-1,3,4-oxadiazol-2-yl)benzamide (17) showed excellent antioxidant activity and exhibited high protection against DNA damage induced by the Bleomycin iron complex.     

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.     

Crystal structures of <Emphasis Type="Italic">trans</Emphasis>-dichlorobis(ethylendiamine) rhodium(III) with univalent anions

The crystal structures of the compounds trans-[Rh(en)₂Cl₂]Cl₂ · H₅O₂ (I), trans-[Rh(en)₂Cl₂]ClO₄ (II), and trans-[Rh(en)₂Cl₂]ReO₄ (III) are determined. The crystal data are: I, a = 10.860(3) Å, b = 7.795(2) Å, c = 9.023(3) Å; β = 111.56(10)°, P2₁/c space group, Z = 4, d _x = 1.875 g/cm³; II, a = 6.593(2) Å, b = 8.309(3) Å, c = 11.922(4) Å, α = 83.55(10)°, β = 79.80(10)°, γ = 75.38(10)°, P \(\bar 1\) space group, Z = 2, d _x = 2.106 g/cm³; III, a = 6.533(2) Å, b = 16.391(4) Å, c = 12.411(3) Å; β = 98.30(10)°, P2₁/c space group, Z = 4, d _x = 2.749 g/cm³. The compounds are examined by IR spectroscopy and powder XRD. The solubility of the isolated crystalline phases in water decreases in the following order: trans-[Rh(en)₂Cl₂]Cl₂·H₅O₂ > trans-[Rh(en)₂Cl₂]ClO₄ > trans-[Rh(en)₂Cl₂]ReO₄.     

Reaction of Imidazoles and Triazoles with 1-(Benzotriazol-1-yl)-2-iodoethanone

Reactions of 2-methyl-1H-imidazole, 1H-benzimidazole, 4H-1,2,4-triazole, and 1H-benzotriazole with 1-(1H-benzotriazol-1-yl)-2-iodoethan-1-one in the absence of a base gave the corresponding N-mono- and N,N′-disubstituted derivatives. 4H-1,2,4-Triazole-3-thiol reacted with 1-(1H-benzotriazol-1-yl)-2-iodoethan-1- one to afford 1-([1,3]thiazolo[2,3-c][1,2,4]triazol-5-yl)-1H-benzotriazolium triiodide.