Search

The crystal structure of a new compound Ca(4-ClC6H4SCH2COO)2·Н2О obtained as a part of the study of biologically active metal protatranes is determined by single crystal X-ray diffraction. The coordination polyhedron of the calcium atom is heptacoordinated; the interatomic distances and atomic packing in the unit cell are analyzed.

Methods for the synthesis of 4-chlorophenylsulfonylacetic acid and its tris(2-hydroxyethyl)ammonium salt (“sulfacetamine”) were studied. The results of in vitro and in vivo experiments showed that sulfacetamine possesses high antithrombotic, antioxidant, hypocholesterolemic, immunostimulating, and protective-adaptive activities.

Difficultly accessible 1-R-indol-3-ylsulfanyl(sulfonyl)acetic acids 1-R-IndYCH2CO2H (R = H, Me, Bn; Y = S, SO2) 1a–Id were prepared. Their reaction with tris(2-hydroxyethyl)amine yielded tris(2-hydroxyethyl) ammonium 1-R-indol-3-ylsulfanyl(sulfonyl)aceetates (protatranes) 2a–2d. The immunoactive properties of 2a–2d were studied. Protatranes 2a, 2c, and 2d proved to be effective immunosuppressive agents (up to 99.5% inhibition of mice splenocyte proliferation in vitro).

Sulfones are known to be biologically active compounds. X-ray diffraction is used to determine the crystal and molecular structure of methyl-(4-chlorophenyl)sulfone. The closest molecules are in pairs oriented to each other by their chlorine atoms. The crystal architecture is formed by endless ribbons of paired associates of the molecules under study.

A number of tris(2-hydroxyethyl)ammonium arylchalcogenylacetates ArYCH2CO2–• •HN+(CH2CH2OH)3 (1—4) (Ar = aryl; Y = O, S, SO2) were synthesized. Their structure was established by IR and 1H, 13C, 15N NMR spectroscopy. The influence of compounds 1—4 on the growth and development of yeast fungi Saccharomyces cerevisiae was studied. Compounds 1—4 were found to be efficient, safe, and available synthetic stimulants of these processes. The use of compounds 1—4 in low concentrations (from 10–8 to 10–4 wt.%, depending on the time of cultivation, concentration, and the anion type) reduced the lag-phases of development and increased the generation rate of yeast cells by 2—5 times. The amount of yeast cells increased by 2—3 times, while the content of protein in the biomass increased by 13—15%. The fermentation of sugar- and starch-containing raw material with yeast Saccharomyces cerevisiae increased the yield of ethyl alcohol (biofuel) by 5—9%.

Highlights • We have synthesized a wide range of tris-(2-hydroxyethyl)ammonium arylchalcogenylacetates, “protatranes”. • “Protatranes” are growth stimulators of hydrocarbon-oxidizing Rhodococcus erythropolis bacteria isolated from Lake Baikal. • The effect of “protatranes” on growth of Pseudomonas fluorescens is less obvious. • The effect of stimulants on Rhodococcus erythropolis is likely due to the structure of protatranes and the cell wall of bacteria., Under natural conditions, biodegradation processes proceed slowly, especially in regions with low temperature. To activate vital processes in hydrocarbon-oxidizing microorganisms at low temperatures, biologically active compounds can be employed as growth stimulants. A low-temperature (10 °C) study has shown that tris-(2 hydroxyethyl) ammonium arylchalcogenylacetates, “protatranes” exert an effect on the growth of hydrocarbon-oxidizing strains of Rhodococcus erythropolis and Pseudomonas fluorescens, isolated from natural oil seepage on Lake Baikal. It has been found that “protatranes”, at microconcentrations, increase the growth rate of R. erythropolis bacteria by 2–16 times. It has been established that compounds slightly effect the growth of P. fluorescens. The positive effect of “protatranes” compounds on the growth rate of hydrocarbon-oxidizing microorganisms at low positive temperatures can be used for the development of environmentally benign methods for the restoration of natural objects after their contamination with oil.

The 1Н, 13С, 15N, and 111Cd NMR spectra of a series of metallated alkanol ammonium ionic liquids (MAIL) series [n N(CН2СН2ОН)3М]+ · mХ−, where М = Cd, Mg, Zn, Fe, Rh; Х = Cl, ООCСН3, obtained in a wide range of temperatures of the studied samples, have been analyzed. It is found that, under biomimetic conditions (Н2О, 25 °С), the compounds studied exist as mono- bi- and the tricyclic structures, which are in equilibrium. Shift of the equilibrium depends upon nature of a metal and effects all the parameters of the NMR spectra. Peculiarities of ligand exchange, typical for the studied compounds, have been studied in a wide range of temperatures. It is found that the NMR data can be used to control structure of the compounds formed in the course of synthesis.

According to the 1Н, 13С, and 15N NMR spectral data, metallated alkanolammonium ionic liquids exist as equilibrium of mono-, bi-, and tricyclic structures under the biomimetic conditions (Н2О, 25 °C). The equilibrium shift depends on the metal nature and affects the change of all parameters in the NMR spectra.

New potentially pharmacologically active complexes of general formula n[(HOCH2CH2)3N—O]·MX2 (M = Zn, Co, Ni, Cu; X = Cl, MeCO2, ArOCH2CO2; n = 1, 2) were synthesized by the reaction of triethanolamine N-oxide with essential metal salts.

The reaction of pharmacological active protic ionic liquid tris-(2-hydroxyethyl)ammonium 4-chlorophenylsulfanylacetate H + N(CH 2 CH 2 OH) 3 ∙ ( - OOCCH 2 SC 6 H 4 Cl-4) (1) with zinc or nickel chloride in a ratio of 2:1 affords stable at room temperature powder-like adducts [H + N(CH 2 CH 2 OH) 3 ] 2 ∙ [M(OOCCH 2 SC 6 H 4 Cl-4) 2 Cl 2 ] 2- , M = Zn (2), Ni (3). By recrystallization from aqueous alcohol compound 2 unexpectedly gives Zn(OOCCH 2 SC 6 H 4 Cl-4) 2 ∙ 2H 2 O (4). Unlike 2, compound 3 gives crystals [N(CH 2 CH 2 OH) 3 ] 2 Ni 2+ · [ - OOCCH 2 SC 6 H 4 Cl-4] 2 (5), which have a structure of metallated ionic liquid. The structure of 5 has been proved by X-ray diffraction analysis. It is the first example of the conversion of a protic ionic liquid into potentially biological active metallated ionic liquid (1 → 3 → 5).

The title compound was prepared by the reaction of 1,4,10,13-tetraoxa-7,16-diazacyclo-octadecane with 4-chloro-2-methyl-phenoxyacetic acid in a ratio of 1:2. The structure has been proved by the data of elemental analysis, IR spectroscopy, NMR (1H, 13C) technique and by X-ray diffraction analysis. Intermolecular hydrogen bonds between the azonium protons and oxygen atoms of the carboxylate groups were found. Immunoactive properties of the title compound have been screened. The compound has the ability to suppress spontaneous and Con A-stimulated cell proliferation in vitro and therefore can be considered as immunodepressant.

The review summarizes the data on the synthesis, physicochemical properties, structure, and pharmacological activity elucidation of salts and ionic liquids synthesized based on 2-hydroxyethylamines, aryl chalcogenylacetic acids, and essential metals. The practical application prospects of these novel compounds in medicine and biotechnology are discussed.

By X-ray diffraction the crystal and molecular structure of N-methyl-bis(2-hydroxyethyl)ammonium (4-chlorphenylsulfonyl)acetate 4-ClC6H4SO2CH2COO−·CH3N+H(CH2CH2OH)2 synthesized by the interaction of (4-chlorphenylsulfonyl)acetic acid with N-methyl-bis(2-hydroxyethyl)amine is studied.

Methods for the synthesis of 4-chlorophenylsulfonylacetic acid and its tris-(2-hydroxyethyl)ammonium salt (sulfacetamine) were developed. Results of in vitro and in vivo experiments showed that sulfacetamine possessed high antithrombotic, membrane-stabilizing, antioxidant, hypocholesterolemic, and adaptogenic activity with low toxicity to animals.

The interaction of ethanolamines Me 3− n N(CH 2 CH 2 OH) n ( n = 1–3) with arylheteroacetic acids Ar Y CH 2 COOH (Ar = 2-CH 3 C 6 H 4 , 4-ClC 6 H 4 ; Y = O, S, SO 2 ) as well as acetic acid itself has been studied. For isolated state, the geometries and electronic structures of the complexes obtained were calculated using DFT method at B3LYP/6-311+G ** level of theory. The energy of the compounds has been calculated by means B3LYP/6-311+G ** and MP2/6-311+G ** //B3LYP/6-311+G ** methods. It has been shown that proton transfer (PT) and hydrogen bonding (HB) complexes are formed from triethanolamine (TEA) and the studied acids, while only НВ complexes is generated from diethanolamine and ethanolamine derivatives. The TEA complexes are stabilized by N H + ⋯O − (PT) or O Н⋯N (HB) hydrogen bonds and O H⋯O bonds of its hydroxyl groups and oxygen atoms of acid. The N H + ⋯О − and О H⋯N bonds in the complexes have a partial covalent character as predicted by the quantum theory of atoms in molecule (QTAIM). According to the second-perturbation energies E (2) in the NBO scheme, highest charge transfer is along the О H⋯N hydrogen bond for HB complexes of TEA with Ar Y CH 2 COOH. The GIAO calculated 15 N NMR chemical shifts are well correlated with NBO electron charges on the nitrogen atom for both type complexes.

A general method for the synthesis of 1-alkyl(allyl)(benzyl)-substituted (indol-3-yl)-sulfanylalkanecarboxylic acids and hexane-1,6-diyl(1,4-phenylenemethylene)bisindol-3-ylsulfanylalkanecarboxylic acids from the corresponding N-substituted indoles and bisindoles, thiourea, iodine, and halogencarboxylic acids was developed. The oxidation of substituted (indol-3-yl)sulfanylalkanecarboxylic acids for the first time afforded their analogs containing the sulfonyl group. New (2-hydroxyethyl)ammonium salts of 1-R-indol-3-ylsulfanyl(sulfonyl)-alkanecarboxylic acids, which are structural analogs of highly active immunomodulators of indacetamin and VILIM, were synthesized. Among the studied (2-hydroxyethyl)ammonium salts of 1-R-indol-3-ylsulfanylacetic and -sulfonylalkanecarboxylic acids, the compounds exhibiting high dose-dependent antiproliferative activity by the ability to affect the spontaneous and mitogen-stimulated splenocyte proliferation of mice in vitro were found.

According to the data of the 15N NMR, IR spectroscopy, and quantum-chemical calculations the products of interaction of chlorides of biogenic metals MCl2 (M = Zn, Ni, Ca) with triethanolammonium salts of acetic and p-chlorophenylsulfanylacetic acids are complexes formed by metal di(p-chlorophenylsulfanylacetates) with protonated triethanolamine via the coordination bonds M…OH.

Quaternary ammonium salts 2(RCH2COO)−·(2H·DACE)+ were synthesized in up to 98% yield by the reaction of biologically active organylheteroacetic acids (OHA) RCH2COOH with diaza-18-crown-6 ether (DACE).

A series of two- and three-component complexes was synthesized of triethanolamine with zinc salts of organylheteroacetic acids, promising biologically active compounds for the search for immunomodulating, antistressor, antitumor, etc. drugs.

A series of previously unknown promising biologically active compounds, complexes of biogenic metal salts, aroxyacetic acid salts, and triethanolamine, were prepared. The structure and acid-base properties of these compounds were studied by NMR and IR spectroscopy and by potentiometric titration.

The reaction of chloroacetyl chloride with 1,2-dichloroethene in the presence of AlCl3 unexpectedly led to the formation of (E)-1,1,4-trichlorobut-3-en-2-one whose structure was proved by 1H and 13C NMR, IR, and mass spectra and independent synthesis. A probable reaction scheme was proposed, which involves transformation of initially formed 1,2,4-trichloro-3-oxobutan-2-yl cation by the action of AlCl3. The high reactivity of the vinylic halogen atom in (E)-1,1,4-trichlorobut-3-en-2-one was demonstrated by its reactions with nitrogen-centered nucleophiles (triethylamine, aniline, 3,5-dimethyl-1H-pyrazole) and sodium sulfide. These reactions involved only the C-Cl bond in the vinyl fragment and afforded (4,4-dichloro-3-oxobut-2-en-1-yl)triethylammonium chloride, 1,1-dichloro-4-phenylaminobut-3-en-2-one, 1-(4,4-dichloro-3-oxobut-2-en-1-yl)-3,5-dimethyl-1H-pyrazole, and 4,4′-thiobis(1,1-dichlorobut-3-en-2-one), respectively. The reaction of 1,1,4-trichlorobut-3-en-2-one with benzylhydrazine gave a mixture of 1,3- and 1,5-disubstituted pyrazoles.

The article gives a survey of methods of synthesis and specific biological activity of hydroxyalkylammonium salts derived from organylsulfanyl(sulfinyl, sulfonyl)acetic acids which can be used as growth stimulators with respect to beneficial bacteria, yeasts, and fungi in large-scale biotechnology processes for manufacture of fodder and baker’s yeasts and citric acid, barley sprouting for the preparation of brewer’s malt, and breeding of silkworms.

(1-Benzyl-1H-pyrrol-2-ylsulfanyl)acetic acid, 2- and 3-(1-benzyl-1H-pyrrol-2-ylsulfanyl)propionic acids, 1,1′-[1,4-phenylenebis(methylene)]bis[(1H-pyrrol-2-ylsulfanyl)acetic acid], and 1,1′-(hexane-1,6-diyl)bis-[(1H-pyrrol-2-ylsulfanyl)acetic acid] were synthesized for the first time by reactions of 1-benzyl-1H-pyrrole, 1,1′-[1,4-phenylenebis(methylene)]bis(1H-pyrrole), and 1,1′-(hexane-1,6-diyl)bis(1H-pyrrole) with thiourea, iodine, and the corresponding halogen-substituted alkanoic acids. 1-(4-Nitrophenyl)-1H-pyrrole failed to react with thiourea and iodine.

A series of complexes of triethanolamine with metal salts of aroxyacetic acids has been prepared. The complexes are perspective biologically active compounds for search for new immunomodulating, antistress, anti-inflammatory and other types of agents. The structure and acid-base properties of these compounds were studied by NMR and IR spectroscopy and potentiometric titration.

Regioselective heterocyclization of alkyl 2-chloro-and 2,2-dichlorovinyl ketones with 1,1-dialkyl-hydrazines to 1,3-dialkyl-1H-pyrazoles and 1,3-dialkyl-5-chloro-1H-pyrazoles involves intermediate formation of the corresponding dialkylhydrazones. Fragmentation pattern of chlorine-containing pyrazoles, 3-chloromethyl-1-methyl-1H-pyrazole and 5-chloro-1-methyl-3-propyl-1H-pyrazole, depends on the position of the halogen atom.

2-Chlorovinyl alkyl ketones react with alkylhydrazines to give mixtures of 1-R-3-R′- and 1-R-5-R′-pyrazoles: The 1-R-3-R′-pyrazoles form through the heterocyclization of 2-chlorovinyl ketone alkylhydrazones whereas in the heterocyclization into 1-R-5-R′-pyrazoles N1-alkyl-N2-(2-acylvinyl)hydrazines are involved. The regiospecific heterocyclization of 2-chloro-and 2,2-dichlorovinyl ketones with arylhydrazines and also of 2,2-dichloro(bromo)vinyl trifluoromethyl ketones with C alkylhydrazines into pyrazoles and 5-chloro(bromo)-pyrazoles proceeds through a stage of haloenones hydrazones formation. The study of the structure of the obtained 1-alkyl-3(5)-alkylpyrazoles by means of two-dimenaional 1H and 13C NMR spectroscopy and GC-MS method made it possible to assign the proton and carbon signals of isomeric pyrazoles and to establish the diagnostic ions for the pair of 1,3-and 1,5-isomers.

N-(2,2-Dichloro-2-phenylethylidene)arenesulfonamides were synthesized by a modified procedure, and their reactions with secondary amines were studied for the first time. Reactions of imines with dialkylamines proceed at room temperature to afford α,α-dichloromethylbenzene and N,N-dialkyl-N′-(arenesulfonyl)formamidines arising from the haloform cleavage of the initially formed unstable N-(1-dialkylamino-2,2-dichloro-2-phenylethyl)arenesulfonamides. When the reaction is carried out upon cooling to 0°C, the products of the nucleophilic addition of secondary amines to azomethines, N-(1-dialkylamino-2,2-dichloro-2-phenylethyl) are formed in yields of no higher than 5%. Nonempirical calculations of 13C-1H spin-spin coupling constants and their experimental measurements for the series of the synthesized N-arenesulfonamides were performed to show that these compounds exist in solutions exclusively as E isomers. Preferable conformations of the investigated compounds and the relative energies of their E and Z isomers in the gas phase were determined by quantum-chemical calculations at the MP2/6-311G** level of theory. The NMR spectral data revealed restricted rotation of the N,N-dialkylamino group about the partially double C-NAlk2 bond in the molecules of N-arenesulfonylformamidines.

Conditions were developed where the reaction of alkyl 1,2-dichlorovinyl ketones with alcohols and 1,2-dihydroxybenzenes led to the formation of the corresponding open-chain and cyclic α-chloro-β-ketoacetals. The reaction of α-chloro-β-alkylketodimethoxyacetals with alkyl-, benzyl-, and arylhydrazines resulted in 1,3-substituted 4-chloropyrazoles in 70–90% yields demonstrating that primarily formed 2,2-dimethoxy-1-chloroethyl alkyl ketones hydrazones underwent heterocyclization.

Reactions of N,N,N′,N′-tetrachlorobiphenyl-4,4′-disulfonamide, 4,4′-methylenebis(N,N-dichlorobenzenesulfonamide), and 4,4′-oxybis(N,N-dichlorobenzenesulfonamide) with 1,2-dichloroethylene and trichloroethylene open convenient synthetic approach to highly electrophilic bissulfony limines of dichloroacetic aldehyde and chloral: N,N′-bis(polychloroethylidene)biphenyl-4,4′-disulfonamides, 4,4′-methylenebis[N-(polychloroethylidene)benzenesulfonamides] and 4,4′-oxybis[N-(polychloroethylidene)benzenesulfonamides]. The synthetic opportunities of the bisazomethines obtained were demonstrated by examples of their reactions with water, methanol, chloroacetamide, and toluene where products of O-, N-nucleophiles addition to the azomethine bond and products of C-amidoalkylation of aromatic compound with imines were formed.

Reaction of aryl-and trifluoromethanesulfonic acids N,N-dichloroamides with tribromoethylene led to the formation of a mixture of N-(2,2-dibromo-2-chloroethylidene)-and N-(2,2,2-tribromoethylidene)amides of the corresponding sulfonic acids. The azomethines ratio is governed by the reaction temperature.

Reactions of alkyl-, allyl-, and arylamines and o-aminophenol with 1,2-dichlorovinyl alkyl ketones involve replacement of only one chlorine atom in the β-position with respect to the carbonyl group with formation of 2-alkylamino-, 2-allylamino-, and 2-arylamino-1-chlorovinyl ketones. Diamines of the aromatic and aliphatic series react with 1,2-dichlorovinyl alkyl ketone molecules to give N,N′-bis(2-acyl-2-chlorovinyl)-substituted diamines.

Immunoactive ionic liquids (2-hydroxyethyl)ammonium 1-R-indol-3-ylsulfanyl-acetates HN+R1R2(CH2CH2OH) ∙ -O(O)CCH2S-Ind-R3-1 (1-5), were synthesized by the reaction of (2-hydroxyethyl)amines with indol-3-ylsulfanylacetic- or 1-benzylindol-3-ylsulfanylacetic acid. 1: R1 = R2 = CH2CH2OH, R3 = H; 2: R1 = СН3,R2=CH2CH2OH, R3 = H; 3: R1 = R2 = CH3, R3 = H; 4: R1 = R2 = CH2CH2OH, R3 = СH2С6Н5; 5: R1 = СН3; R2 = CH2CH2OH; R3 = СH2С6Н5. The structure of each compound was elucidated by IR, NMR 1H, 13С, and 15N techniques and their composition was confirmed by elemental analysis. The crystal structure of tris-(2-hydroxyethyl) ammonium indol-3-ylsulfanylacetate was investigated by X-ray diffraction analysis. Immunoactive properties of the title compounds were screened.

Hydrolytic transformations of 4-[2,2,2-trichloro-1-(arylsulfonylamino)-and-(ethoxycarbonylamino)ethyl]phenyloxy(or sulfanyl)acetic acids under microwave irradiation in alkaline medium involve both trichloromethyl group and ester fragment to give N-arylsulfonyl-2-[4-carboxymethyloxy(or sulfanyl)phenyl]-2-aminoacetic acids in good yields. Hydrolysis of methyl 4-[2,2,2-trichloro-1-(arylsulfonylamino)ethyl]phenyloxy(or sulfanyl)acetates without microwave activation occurs only at the ester group with quantitative formation of 4-[2,2,2-trichloro-1-(arylsulfonylamino)ethyl]phenyloxy(or sulfanyl) acetic acids. N-[2,2,2-Trichloro-1-(1-naphthyl, 2-furyl, and 1-methylindol-3-yl)ethyl]-4-chlorobenzenesulfonamides in alkaline medium under microwave irradiation were converted in 10–15 min into the corresponding N-(4-chlorophenylsulfonyl)-2-aryl-2-aminoacetic acids in preparative yields.

The nitration of 5-chloropyrazoles with a mixture of 100% nitric acid and 65% oleum or a mixture of 60% nitric acid and polyphosphoric acid gave substituted 5-chloro-4-nitropyrazoles in 45–91% yield. The nitration of 3-aryl-5-halopyrazoles was accompanied by introduction of a nitro group into the aromatic ring. 4-Chloropyrazoles failed to undergo nitration under these conditions. The reaction of 5-chloro-1,3-dimethyl-4-nitropyrazole with ethyl cyanoacetate in DMSO in the presence of K2CO3 led to the formation of ethyl 2-cyano-2-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)acetate.

The interaction of N -(1-aryl-2,2,2-trichloroethyl)amides of arenesulfonic acids with secondary amines or their salts in the presence of inorganic bases involves the formation of chloroaziridine intermediates. Depending upon the solvent and reagent ratio, the reaction results in N -[1-dialkylamino-2-chloro-2-arylethylidene]-, N -[2-dialkylamino-1-chloro-2-arylethylidene]-, N -[1,2-bis(dialkylamino)-2-arylethylidene]-, and N -(1,2-dioxo-2-arylethene)amides of arenesulfonic acids.

A method has been developed for obtaining 3-alkyl(phenyl)-4(5)-chloro-1-(2,4-dinitrophenyl)pyrazoles from appropriate dinitrophenylhydrazones of 1-chloro-, 1,2-, and 2,2-dichlorovinyl ketones by heating the latter in polyphosphoric acid. The structure of the pyrazoles was studied by IR and 1H NMR spectroscopy.

Reactions of trifluoromethanesulfonic acid N-(2,2,2-trichloroethylidene)amide with 1,3-dialkyl-5-chloropyrazoles and 1-phenyl-3-methylpyrazole afforded 4-(amidotrichloroethyl)-substituted pyrazole derivatives. 4-Chloropyrazoles were not involved into this process. The structure of compounds synthesized was studied by means of IR and NMR spectroscopy. The presence of intra- and intermolecular hydrogen bonds was revealed by a decrease in the absorption frequencies and a complicated form of ν(NH) and νas(SO2) absorption bands in the IR spectra, and also in splitting of signals in 1H and 13C NMR spectra.

New potentially pharmacologically active tris(2-hydroxyethyl)hydroxyammonium salts were synthesized by the reaction of triethanolamine N-oxide with biologically active acetic acid derivatives RYCH2CO2H (R = Ar, 3-indolyl; Y = O, S, SO2).

C-Amidoalkylation of aroxy- and arylsulfanylacetic acids and their methyl esters was effected by reaction with N-(2,2,2-trichloro-1-hydroxyethyl)sulfonamides and -carboxamides in the presence of methane- or trifluoromethanesulfonic acids as catalyst and solvent. The process is regioselective, and the substitution occurs at the para-position with respect to the heteroelement-containing group.