Russian Journal of Organic Chemistry最新文献

A procedure has been developed for the synthesis of 3,5-difluoroadamantan-1-yl isocyanate from 3,5-difluoroadamantane-1 carboxylic acid and diphenylphosphoryl azide using a new fluorinating agent, Ishikawa reagent, in one stage of the synthesis. The reaction of 3,5-difluoroadamantan-1-yl isocyanate with aliphatic diamines and trans-4-[(4-aminocyclohexyl)oxy]benzoic acid afforded a series of N,N′-disubstituted ureas and bis-ureas in 43–96% yields. The hydrolysis of 3,5-difluoroadamantan-1-yl isocyanate in the presence of a catalytic amount of DBU gave symmetrical N,N′-bis(3,5-difluoroadamantan-1-yl)urea in 47% yield. A relation between the number of fluorine atoms in the adamantane fragment on the melting points and lipophilicities of the synthesized ureas has been revealed, which makes it possible to control these important properties of ureas as potential enzyme inhibitors.

The review considers the mechanism of intramolecular cyclization (intramolecular Diels–Alder reaction) of quaternary ammonium salts simultaneously containing β,γ-unsaturated and various enyne fragments.

Over the past two decades, acridinediones have attracted considerable attention in organic and medicinal chemistry, drug discovery, and materials science. The present review covers recent literature on the synthesis of acridine-1,8-dione derivatives, including cyclocondensation and multicomponent reactions. These compounds exhibit significant biological activity and have found application in the production of antimicrobial, anticancer, and anti-inflammatory drugs. They are also used in materials science, acting as fluorescent probes. Recent advancements have been focused on developing more efficient synthetic approaches to acridine-1,8-diones and exploring novel applications. The versatility and wide range of functionalities make acridine-1,8-dione derivatives valuable in both pharmaceutical and industrial fields, highlighting their potential for future research and development.

A new procedure for the synthesis of novel ketonitrones has been developed. The procedure involves the coupling of Grignard reagents with the easily accessible and stable N-substituted α-(1H-benzotriazol-1-yl) nitrones in the presence of catalytic amounts of zinc bromide.

The review summarizes, systematizes, and analyzes the published data concerning the reactions of saturated and unsaturated oxazol-5(4H)-ones with various organosilicon reagents. Examples of the synthesis of heterocyclic compounds, 4,4-disubstituted oxazol-5(4H)-ones, and α,α-disubstituted α-amino acids and their esters by these reactions are considered. For some processes, plausible mechanisms are presented. Examples of the synthesis of biologically active and natural compounds based on reactions involving oxazol-5(4H)-ones and organosilicon reagents are described.

Dialkyl(4-hydroxybut-2-ynyl)(3-phenylprop-2-enyl)ammonium bromides in the presence of catalytic amounts of aqueous alkali do not undergo intramolecular [4+2]-cyclization of the diene synthesis type, because the 3-phenylprop-2-enyl group does not take part in the reaction as a diene fragment, and the initial salts are formed again. In the presence of a double amount of aqueous alkali, contrary to our expectations, the salts undergo Stevens rearrangement with transfer of the reaction center in both the host and migrating groups, followed by intramolecular cyclization rather than intramolecular cyclization–recyclization.

This paper presents an efficient and practical protocol for the synthesis of rufinamide (anti-epileptic drugs) active pharmaceutical ingredient (API) and several process impurities by a 1,3-dipolar cycloaddition reaction, starting from commercially available benzyl bromides. The earlier reported syntheses of rufinamide had encountered challenges in isolating by-products from the mother liquor. In this work, the impurities were synthesized via the retrosynthesis route to serve as reference samples for assessing the purity level of drugs. These impurities, characterized by the presence of N-group and azole derivatives, find wide-range applications in academic and industrial settings, including organic synthesis, drug discovery, polymer chemistry, chemical biology, and supramolecular chemistry. The primary objective of this synthesis was to propose a reliable and pragmatic method for producing rufinamide and its impurities to address diverse scientific and industrial requirements. The protocol outlined in this research aims to contribute to the development of robust methodologies for the synthesis of pharmaceuticals and associated impurities, with potential implications for drug development and chemical research.

A method for the synthesis of 2-amino-3-(3,4-dihydroxyphenyl)propanoic acid (dioxyphenylalanine, DOPA), a racemic form of the antiparkinsonian drug Levodopa and a biosynthetic precursor of melanins, was developed. The synthesis involves 3 stages, and an overall yield of the target product 59%, which is higher than in the previously reported syntheses. At the first stage, 3,4-dimethoxybenzaldehyde was introduced in condensation reaction with benzoylglycine to obtain azlactone with 83% yield. The subsequent hydrolysis and reduction by Raney alloy in an alkaline medium, carried out in one stage, gave 3-(3,4-dimethoxyphenyl)-2-(benzoylamino)propanoic acid with 90% yield. Further, the removal of the protective groups with hydrobromic acid followed by treatment with aqueous ammonia resulted in the formation of 2-amino-3-(3,4-dihydroxyphenyl)propanoic acid with 80% yield. The structure of all the synthesized compounds was confirmed by NMR and IR spectroscopy and elemental analysis, as well as by the X-ray diffraction analysis of (Z)-2-benzamido-3-(3,4-dimethoxyphenyl)acrylic acid, an intermediate in the synthesis of DOPA.

Novel 5'-methylamino-2'-nitro-m-terphenyls were obtained by the rearrangement of quaternary nitropyridinium salts under the action of aqueous alcoholic alkali and aqueous methylamine. Hantzsch 4-aryl-2-methyl-5-nitro-6-phenyl-1,4-dihydropyridines obtained by the cyclocondensation of nitrochalcones with various enamines were used as starting compounds. The oxidation of 1,4-dihydropyridines with sodium nitrite in acetic acid gave 4-aryl-2-methyl-5-nitro-6-phenylpyridines. The synthesized nitropyridines were alkylated with dimethyl sulfate and methyl fluorosulfonate.

The amination of 1,4-benzoquinone monoxime and 5-(hydroximino)quinoline-8(5H)-one with diamines H₂N-R-NH₂ [R = -(CH₂)₂-; -(CH₂)₄-; and trans-cyclohexane-1,4-diyl] gave the corresponding N,N'-bis(4-nitrosophenyl)diamines and N,N'-bis(5-nitrosoquinolin-8-yl)diamines. Stable alkane- and cycloalkanediammonium salts of 1,4-benzoquinone monooxime and 5-(hydroximino)quinolin-8(5H)-one were synthesized.