Nitration of 3-Methylaceperidazines with a Large Excess of Fuming Nitric Acid

Nitration of N-acetyl-3-methylaceperidazine with a 2–3-fold excess of nitric acid (d 1.36, 1.48) in glacial acetic acid results in the exclusive formation of mono- and dinitroderivatives. The nitration of 3-methylaceperidazine and its N-alkyl- and N-acetyl-substituted derivatives with a 6–9-fold excess of fuming nitric acid (d 1.54) in the same conditions results in the formation of both the expected products of mono- and dinitration and a product of the electrophilic addition of nitric acid to a double bond of acenaphthene scaffold of the molecule of nitration product.     

Epoxidation and Heterocyclization of Arenesulfonamides of the Norbornene Series

Reactions of previously known and newly synthesized N-(bicyclo[2.2.1]hept-5-en-endo-2-ylmethyl)arenesulfonamides with monoperoxyphthalic acid generated in situ from phthalic anhydride and 30% hydrogen peroxide lead mostly to the corresponding N-arylsulfonyl-exo-2-hydroxy-4-azatricyclo[4.2.1.0^3,7]nonanes (azabrendanes). In some cases, N-(exo-5,6-epoxybicyclo[2.2.1]hept-5-en-exo-2-ylmethyl)arenesulfonamides were isolated as the only products or mixtures of alternative oxidation products were obtained. The presence of electron-acceptor nitro groups in the benzene ring and bulky substituents, primarily in the ortho position, is considered to be a structural factor preventing the primary oxidation products (epoxy derivatives) from undergoing heterocyclization.     

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.     

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.     

Analytical Methods for the Determination of <Emphasis Type="Italic">Alternaria</Emphasis> Mycotoxins

The genus Alternaria comprises ubiquitous pathogens and saprophytes. They can even grow at low temperature, so they are the main fungi responsible for the spoilage of various fruits, vegetables, grains and their products during long-distance transport and refrigerated storage. Alternaria mycotoxins are the secondary metabolite of the genus Alternaria. They can be divided into five main classes according to their chemical structures, including dibenzopyrone derivatives, tetramic acid derivatives, perylene derivatives, AAL toxins and miscellaneous structures. Alternaria mycotoxins are associated with many health effects because of their mutagenicity, teratogenicity and carcinogenicity, which can cause economic losses to agriculture and serious diseases in humans and animals. So far, there is still a lack of monitoring data on these contaminants of Alternaria mycotoxins. Moreover, there are still no statutory or guideline limits set for Alternaria mycotoxins in food and feed by regulatory authorities worldwide. Until now, many analytical methods have been developed for the detection and quantification of Alternaria mycotoxins. On the basis of briefly introducing the chemical structures and toxicities of Alternaria mycotoxins, this article provides an overview of the progress achieved in the detection techniques for Alternaria mycotoxins, focusing on the analytical methods of thin layer chromatography (TLC), gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS), liquid chromatography (LC), liquid chromatography-mass spectrometry (LC-MS), enzyme-linked immunosorbent assay (ELISA) and so on. Finally, the problems of these analytical methods and future development trends are discussed.     

5-Trifluoromethylfuryl derivatives of phosphocarboxylic acids

Methods of synthesis of trifluoromethylfuryl derivatives of phosphonocarboxylic acids are studied. By addition of diethyl hydrogen phosphite to alkyl 3-(5-trifluoromethylfur-2-yl)acrylate under the conditions of the Pudovik reaction the corresponding derivative of 3-phosphonopropionic acid was prepared. Diethyl (5-trifluoromethylfur-2-yl)methanephosphonate in presence of potassium tert-butylate reacts with ethyl acrylate to form trifluoromethylfuryl derivative of 4-phosphonobutyric or 4-phosphonopimelic acid depending on the reaction conditions. In the products of reaction of the alkyl 3-(5-trifluoromethylfur-2-yl)-3-(diethoxyphosphoryl) propionate with ethyl acrylate in the presence of potassium tert-butylate formation of trifluoromethylfuryl derivative of the 3-phosphonoadipic acid is detected. 3-(5-Trifluoromethylfur-2-yl)-3-(diethoxyphosphoryl) propionic acid and its acid chloride are synthesized. The latter compound is used for acylation of glycine to form the corresponding N-acyl derivative. It is suggested that such compounds may be transported in the cell using usual channels of transportation of the amino acids and short peptides.     

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.     

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.     

Rearrangements of <Emphasis Type="Italic">N</Emphasis>-ethoxycarbonylmethyl-1,2,3,4-tetrahydroquinolinium halogenalkylates effected by sodium hydride. Synthesis of 2,3,4,5-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-3-benzazepines

Quaternary salts obtained from N-alkyl-1,2,3,4-tetrahydroisoquinolines and ethyl haloacetates or diethyl bromomalonate under the action of sodium hydride in boiling 1,4-dioxane were converted into N-alkyl-N-ethoxycarbonyl-2,3,4,5-tetrahydro-1H-3-benzazepines in 49–60% yield. From the reaction mixture by column chromatography products of β-elimination by Hofmann reaction, 2-(N-methyl-N-ethoxycarbonylmethyl)-aminomethylstyrenes were also isolated (yield 0.6–16%).     

Reaction of anthranilic acid 2-<Emphasis Type="Italic">N</Emphasis>-phenylhydrazide with cyclic anhydrides

In the reaction with cyclic anhydrides the anthranilic acid 2-N-phenylhydrazide depending on conditions yielded either anthranilic acid 2-N-acyl-2-N′-phenylhydrazides, 2-R-3-anilinoquinazolin-4(3H)-ones, or derivatives of 1-phenylpyridazino[3,2-b]quinazoline-2,10-dione.     

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 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.     

Nitration of 3-methyl-6,7-dihydro-1<Emphasis Type="Italic">H</Emphasis>-indeno[6,7,1-<Emphasis Type="Italic">def</Emphasis>]cinnoline and its <Emphasis Type="Italic">N</Emphasis>-substituted derivatives

The nitration of 3-methylaceperidazine (3-methyl-6,7-dihydro-1H-indeno[6,7,1-def]cinnoline) and its N-substituted derivatives with nitric acid of different concentrations requires harsh conditions and is accompanied by dehydrogenation and dimerization of the initial compound.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-acetyl- and <Emphasis Type="Italic">N</Emphasis>-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with <Emphasis Type="Italic">meta</Emphasis>-cloroperbenzoic acid

Reaction of N-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with meta-cloroperbenzoic acid leads to the corresponding 2-[1-o-(3-chlorobenzoyl)-2-hydroxycyclopent-1-yl]anilines. 5-(2-Acetylaminophenyl)-5-oxopentanic or 6-oxohexanic acids are formed as main products in the reaction of N-acetyl-2-(1-cycloalken-1-yl)anilines with m-chloroperbenzoic acid in CH₂Cl₂. N-Acetyl-2-(1-cyclopenten-1-yl)-3,6-dimethylaniline is an exception in this series since its reaction stops at the stage of epoxide formation.     

Reaction of N-substituted 2,5-dialkyl-1,4-benzoquinone imines with arenesulfinic acids

Reactions of N-aroyl-, N-arylsulfonyl-, and N-(N-arylsulfonylbenzimidoyl)-2,5-dialkyl-1,4-benzoquinone imines with sodium arenesulfinates in acetic acid gave the corresponding 1,4-, 6,1-, and 1,6-addition products. Variation of the size and donor power of substituents in positions 2 and 5 of the quinoid ring almost does not affect the ratio of the addition products, which is determined mainly by the nature of substituent on the nitrogen atom.     

Synthesis of benzimidazolone derivatives based on 2-acylcyclohexane-1,3-diones alkoximes

2-(1-Alkoxyiminoalkyl)cyclohexane-1,3-diones undergo at heating Beckmann rearrangement to give 6,7-dihydro-1,3-benzoxazol-4(5H)-one derivatives that under treatment with amines in acid medium are converted into 1,5,6,7-tetrahydro-4H-benzimidazol-4-ones. In reaction of 6,7-dihydro-1,3-benzoxazol-4(5H)-ones with O-ethylhydroxylamine 4-ethoxyimino derivatives were obtained that treated with hydrochloric acid formed the corresponding N-ethoxybenzimidazolones.     

Diastereoselective synthesis of novel <Emphasis Type="Italic">N</Emphasis>-substituted pyrrolidine-2-one containing piperazine derivatives

Synthesis of novel hybrid derivatives of two known scaffolds, pyrrolidine-2-one and piperazine, is described. Initially, the Ugi reaction of phenylglyoxal, aromatic amines, coumarin-3-carboxylic acid and isocyanides in methanol resulted in the formation of dihydrochromeno[3,4-c]pyrrole-3,4-diones. The obtained products were then treated with N-alkylpiperazines in dichloromethane to afford the novel N-substituted pyrrolidine-2-one containing piperazine derivatives in satisfactory yields. The proof of the structures was carried out by means of spectroscopic information and X-ray crystallography.     

Thermodynamics of the Protonation of an Analogue of Glyphosate, <Emphasis Type="Italic">N</Emphasis>-(phosphonomethyl)-<Emphasis Type="SmallCaps">l</Emphasis>-proline,in Aqueous Solutions

N-(phosphonomethyl)-l-proline is an analogue of glyphosate. The protonation for N-(phosphonomethyl)-l-proline was studied by potentiometry, calorimetry, ³¹P NMR spectroscopy and quantum chemical calculations to further understand the protonation process of glyphosate. The results confirmed that the order of successive protonation sites of totally deprotonated N-(phosphonomethyl)-l-proline are a phosphonate oxygen, amino nitrogen, and finally the carboxylate oxygen. The results can improve the understanding of the biological activity of these types of molecules in solution.     

Acyl iodides in organic synthesis. Reactions of acetyl iodide with urea,thiourea, and their <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>′-disubstituted derivatives

Acetyl iodide reacted with urea and its derivatives to give the corresponding N-substituted products. The reactions of acetyl iodide with thiourea, N,N′-dimethylthiourea, imidazolidine-2-thione, and hexahydropyrimidine-2-thione resulted in the formation of S- or N-acetyl derivatives, depending on the temperature and structure of the sulfur functionality (thione or thiol). By contrast, in the reaction of acetyl iodide with N,N′-bis(3-triethoxysilylpropyl)thiourea one ethoxy group on the silicon atom was replaced by iodine with formation of N-{3-[(diethoxy)iodosilyl]propyl}-N′-[3-(triethoxysilyl)propyl]thiourea. The latter decomposed on heating to give 3-triethoxysilylpropyl isothiocyanate and silicon-containing polymer with the composition C₄₅H₉₇IN₆O_14.5S₃Si₆.     

Efficient access to novel tetra- and pentacyclic dihydroquinolin-2-ones by catalyst-free domino Knöevenagel hetero-Diels–Alder reactions from <Emphasis Type="Italic">N</Emphasis>-(2-formylphenyl)-<Emphasis Type="Italic">N</Emphasis>-methylcinnamamides and cyclic 1,3-dicarbonyls in water

An efficient catalyst-free synthesis of novel annulated hybrid derivatives of two known scaffolds, dihydroquinolinone and pyranopyranone, pyranopyrimidinedione, pyranocoumarin or chromenone is described. N-(2-Formylphenyl)-N-methylcinnamamides underwent a one-pot domino Knöevenagel hetero-Diels–Alder reaction with dimedone, N,N-dimethylbarbituric acid, 1,3-indanedione, 4-hydroxycoumarins and 4-hydroxy-6-methyl-2H-pyran-2-one in water, affording the desired tetra and pentacyclic pyranoquinolinones in excellent yields.