Synthesis and biological activity of hydrazones of <Emphasis Type="Italic">o</Emphasis>- and <Emphasis Type="Italic">p</Emphasis>-hydroxybenzoic acids. Spatial structure of 5-Bromo-2-hydroxybenzylidene-4-hydroxybenzohydrazide

A series of hydrazones based on hydrazides of o- and p-hydroxybenzoic acids have been prepared. N-(5-Bromo-2-hydroxybenzylidene)-4-hydroxybenzohydrazide has been studied by X-ray diffraction analysis; its molecule forms hydrogen bond with a solvating ethanol molecule. Biological activity of the synthesized hydrazones towards cathepsin Е and(or) elastase of human neutrophils has been determined.     

Synthesis and properties of ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-3-carboxylates

Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates reacted with phenylhydrazine to give the corresponding hydrazones, ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1H-pyrazole-3-carboxylates, which were converted to ethyl 1′-aryl-4-formyl-5′-methyl-1-phenyl-1H,1′H-3,4′-bipyrazole-3′-carboxylates by treatment with the Vilsmeier–Haack reagent. No indole derivatives were formed from the same hydrazones under the Fischer reaction conditions, but cyclization to 2-aryl-3,4-dimethyl-6-phenyl-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-ones was observed.     

2-Halobenzoyl chlorides in the synthesis of [1,3,4]thiadiazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]quinazolin-5-one derivatives

New nitro and sulfonamide derivatives of [1,3,4]thiadiazolo[3,2-a]quinazolin-5-one have been synthesized by cyclocondensation of 1,3,4-thiadiazol-2-amines with 2-halobenzoyl chlorides containing electron-withdrawing substituents in positions 3, 4, and 5. An improved procedure has been proposed for the preparation of intermediate 2-fluoro-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamides containing a sulfamoyl group in the 5-position via selective acylation of 5-methyl-1,3,4-thiadiazol-2-amine with 5-chlorosulfonyl-2-fluorobenzoyl chloride, followed by sulfonylation of amines.     

Ultrasound-assisted synthesis of pyrazolo[1,2-<Emphasis Type="Italic">b</Emphasis>]phthalazines and dihydrospiro[indoline-3,1'-pyrazolo[1,2-<Emphasis Type="Italic">b</Emphasis>]phthalazines] using TBAF as an efficient phase-transfer catalyst

Tetrabutylammonim fluoride has been used as an efficient catalyst for synthesis of pyrazolo[1,2-b]-phthalazine-5,10-diones and dihydrospiro[indoline-3,1'-pyrazolo[1,2-b]phthalazines] by one-pot three-component reaction of phthalhydrazide, aromatic aldehydes or isatin derivatives, with malononitrile in water under ultrasond irradiation. This rapid method gave the products in high yield.     

Synthesis of 6-methyl-2-[2-phenyl-2-(arylhydrazono)ethyl]-3<Emphasis Type="Italic">Н</Emphasis>-pyrimidine-4-ones and their oxidation by hydrogen peroxide and selenium dioxide

The reaction of 6-methyl-2-(2-oxo-2-phenylethylidene)-2,3-dihydropyrimidine-4(1H)-one with arylhydrazines leads in high yields to the corresponding hydrazones, in which the ethylidene fragment of the starting compound is transformed to the ethylene fragment. By oxidation of the hydrazones with hydrogen peroxide or selenium dioxide the corresponding 6-methyl-2-[2-phenyl-2-(arylhydrazono)acetyl]-3H-pyrimidine-4-ones were synthesized.     

Chemistry of 1,5-diketones: V. Hydrazination of acyclic and heterocyclic (poly)carbonyl compounds

Reactions of 2-(1-aryl-3-oxo-3-phenylpropylidene)-3,4-dihydronaphthalen-1(2H)-ones, 3-(1-aryl-3-oxo-3-phenylpropyl)-3,4-dihydro-2H-chromene-2,4-diones, and 3,3'-(arylmethylene)bis(3,4-dihydro-2H-chromene-2,4-diones) with hydrazine hydrate have been studied. Depending on the substrate structure, these reactions involve intramolecular heterocyclization with participation of the exocyclic double bond and sidechain carbonyl group or both oxo groups to give new pyrazole, indazole, and diazepine derivatives, as well as hydrazones.     

<Emphasis Type="Italic">N</Emphasis>′-tetrazolylmethoxyl derivatives of <Emphasis Type="Italic">N</Emphasis>-methyldiazene <Emphasis Type="Italic">N</Emphasis>-oxides

A preparation method was developed for previously unknown tetrazole derivatives containing in the 1, 2, and/or 5 positions of the tetrazole ring N-methyldiazene-N-oxide-N′-oxymethyl groups.     

Click chemistry methodology in the synthesis of anabasine and cytisine conjugates with isoxazole derivatives

Cytisine and anabasine derivatives containing an acetylenic fragment were used as building blocks in 1,3-dipolar cycloaddition reactions with substituted N-hydroxybenzenecarboximidoyl chlorides, catalyzed by copper(I) salt. The reactions with N-propargylcytisine were not selective, and the products were mixtures of 3,5-disubstituted isoxazoles and small amounts (5–8%) of 3,4-disubstituted isomers. 1,3-Dipolar cycloaddition with N-propargylanabasine afforded 3,5-disubstituted isoxazole derivatives with high regioselectivity.     

Bis[1,3]thiazolo[4,5-<Emphasis Type="Italic">f</Emphasis>:5',4'-<Emphasis Type="Italic">h</Emphasis>]thieno[3,4-<Emphasis Type="Italic">b</Emphasis>]quinoxaline Derivatives as New Building Blocks of Polymers for Organic Electronics

New derivatives of bis[1,3]thiazolo[4,5-f:5',4'-h]thieno[3,4-b]quinoxaline containing the fused thiadiazoloquinoxaline moiety have been prepared. Monomer M1 shows strong light absorption within 600–800 nm due to intramolecular charge transfer. The optical bandgap E _g ^opt determined from the absorption edge in a film is 1.44 eV. The HOMO and LUMO levels are–5.44 and–3.12 eV, respectively. The new structural fragment has a rather low frontier molecular orbital energies and a small bandgap; therefore, it is a promising building block for the synthesis of polymers for organic electronics.     

Azines and azoles: CXXV. New regioselective synthesis of 1-amino-6-methyluracils

Readily accessible 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione reacts with substituted hydrazines and carboxylic acid hydrazides under mild conditions to give the corresponding hydrazones. Under severe conditions (heating in boiling dimethylformamide) the reaction is accompanied by extrusion of COS with formation of substituted 1-amino-6-methyluracils. Reactions of 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione with monosubstituted alkyl-and arylhydrazines take different pathways, depending on the conditions. Heating of equimolar mixtures of the reactants in ethanol or propan-1-ol leads to the formation of 2-substituted 5-methyl-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxamides rather than 1-amino-6-methyluracil derivatives.     

Synthesis of new hydrazones based on <Emphasis Type="Italic">o</Emphasis>- and <Emphasis Type="Italic">p</Emphasis>-hydroxybenzohydrazides

o- and p-Hydroxybenzohydrazides reacted with various unsaturated aromatic aldehydes to give the corresponding N′-(hydroxybenzoyl)hydrazones. Inhibitory activity of the obtained hydrazones against cathepsin E was evaluated.     

Sensitive RP-HPLC Enantioseparation of (<Emphasis Type="Italic">RS</Emphasis>)-Ketamine via Chiral Derivatization Based on (<Emphasis Type="Italic">S</Emphasis>)-Levofloxacin

Enantioseparation of (RS)-ketamine has been achieved in the form of its diastereomeric hydrazones. A new chiral reagent was synthesized from enantiomerically pure (S)-levofloxacin by converting its carboxyl group into a hydrazide derivative: the reagent provided a reaction site for the ketonic group present in (RS)-ketamine. Because of the structural feature of the chiral reagent formation of diastereomeric hydrazones of (RS)-ketamine was successful without protection of its amino group. The diastereomeric hydrazones were separated on a reversed-phase C₁₈ column with a mobile phase consisting of MeCN and 0.1% TFA under gradient elution from 35 to 65% of MeCN. The limit of detection was found to be 3.2 and 3.4 nmol for first and second eluting diastereomeric hydrazones, respectively. The separation mechanism and elution order of the diastereomeric hydrazones were proposed and supported by developing the geometry optimized ‘lowest energy’ structures of the two diastereomeric hydrazones using DFT-based Gaussian software.     

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.     

Synthesis of Macrocyclic Stereoisomers Substituted with Oligolactide Fragments

Acylation of cone and 1,3-alternate stereoisomers of hydrazides of p-tert-butylthaicalix[4]arene tetrasubstituted at the lower rim with S,S-lactide in dimethylsulfoxide has afforded the macrocyclic oligolactide derivatives containing 16 (cone) to 24 (1,3-alternate) lactide fragments. It has been shown that nanosized aggregates (80 nm) are formed with silver nitrate in the case of the cone stereoisomer containing the oligolactide fragments at one side of the macrocyclic rim, whereas submicron particles (400 nm) are formed in the case of the 1,3-alternate conformation when the substituents are at different sides of the macrocycle.     

Addition of phthalimide and acetone to phosphorylated methylene quinones

New method for synthesis of phosphorylated methylene quinones via bromination of the sterically hindered phenol [prepared via benzylation of secondary chlorophosphines with 4-(methoxymethyl)-2,6-di-tert-butylphenol] with N-bromosuccinimide followed by dehydrobromination with trimethyl orthoformate has been developed. Tertiary phosphine oxides containing the fragment of sterically hindered phenol and amine or acetonyl group have been synthesized for the first time in the reaction of phosphorylated methylene quinones with N- and C-nucleophiles.     

Synthesis,characterization, and antimicrobial activities of palladium Schiff base complexes derived from aminosalicylic acids

Six Schiff base compounds have been prepared from the condensation of o-vanillin, 2,3-dihydroxybenzaldehyde and 2,3,4-trihydroxybenzaldehyde with 4-aminosalicylic acid and 5-aminosalicylic acid (5-ASA). Addition of these Schiff bases to [Pd(OAc)₂] afforded the corresponding bis(salicylaldiminato)palladium(II) complexes in moderate to excellent yields. All new palladium complexes have been characterized fully using standard spectroscopic methods, elemental analyses and a single-crystal X-ray diffraction study in the case of 2e, the palladium complex containing Schiff base ligands derived from 5-ASA and 2,3-dihydroxybenzaldehyde. All derivatives of 5-ASA were examined for potential antimicrobial activities against two species of fungi, Aspergillus niger and Saccharomyces cerevisiae, as well as two species of bacteria, Bacillus cereus (Gram-positive) and Pseudomonas aeruginosa (Gram-negative).     

Reactivity of double bonds of substituted <Emphasis Type="Italic">p</Emphasis>-(methacryloyloxy)-<Emphasis Type="Italic">N</Emphasis>-phenylmaleimides in free-radical polymerization

The thermoinduced free-radical polymerization of model systems, namely, methyl methacrylate and N-phenylmaleimide derivatives, has been studied. It has been shown that, in the polymerization of p-(methacryloyloxy)-N-phenylmaleimides, the yield of the polymer and its molecular-mass distribution (mono-or bimodal) and polydispersity depend on the degree of substitution and the nature of a substituent in a double bond of a maleimide fragment. The structure of the maleimide fragment, in turn, determines its capability to copolymerize with the methacryloyl group of a bifunctional monomer as well as the occurrence of chain-transfer and termination reactions.     

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.     

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.     

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.