Research on five-membered heterocycles

Replacement of the nitro group in polynitroimidazoles by a halogen atom by the action of POBr₃ in dimethylformamide or by means of hydrohalic acids was studied. It is shown that the second method is the most convenient method in the preparation of chloro- and bromonitroimidazoles.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1666–1668, December, 1977.     

Research on five-membered heterocycles

Nitrochloroimidazoles were synthesized by replacement of the nitro group in dinitroimidazoles by chlorine by the action of POCl₃. It is shown that in the case of 4,5-dinitroimidazoles substitution takes place when both dimethylformamide (DMF) and pyridine are used as the solvents, while only DMF is suitable for 2,4-dinitroimidazoles. The location of the halogen in the synthesized nitrochloroimidazoles was confirmed by alternative synthesis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, May, 1977.     

Bioisosteric equivalence of five-membered heterocycles

A variety of factors can affect bioisosteric relationships between structural motifs in a medicinal chemistry optimization project, both in terms of ligand affinity to a given target and off-target profile. Such parameters, e.g. the ability to participate in hydrogen bonding and π–π interactions, basicity, and solubility are discussed with a particular focus on five-membered heterocycles and their application in drug design.     

Nickel-catalyzed synthesis of five-membered heterocycles

In recent decades, a large number of reports related to the synthesis of N-, O- and S-containing heterocycles have appeared owing to a wide variety of their biological activity. The investigation of methods for the chemical synthesis is a growing area of interest due to increasing environmental issues. The use of catalysts in organic reactions has gained extensive interest. Metal and nonmetal catalysts provided a new improved alternative to traditional methods in modern synthetic chemistry. The aim of present review is to focus on the applications of nickel for the synthesis of five-membered heterocylces.     

New five-membered nitrogen and phosphorus heterocycles

Conclusions Substituted 2,5-dioxo-1,2-azaphospholanes have been obtained by the reaction of ethyl--chloroformylethylphosphinyl and ethyl--chloroformylpropylphosphinyl chlorides with primary amine in the presence of triethylamine.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1375–1378, June, 1968.     

σ Derivatives of cyclopentadienyldicarbonyliron with five-membered heterocycles

Russian Chemical Bulletin -     

Lightfast filter dyes derived from five-membered heterocycles

The lightfastness of new potential filter dyes derived from furan and pyrazole in three polymer matrices, cellulose acetobutyrate, poly(methyl methacrylate), and styrene-acrylonitrile copolymer, was studied.     

The magnetic circular dichroism of five-membered ring heterocycles

The MCD spectra of pyrrole, furan, thiophene, selenophene and teburophene and some of their derivatives are reported and the corresponding energies, oscillator strengths, transition moment directions, and MCD terms are calculated from semi-empirical quantum mechanical calculations hi the π-electron approximation. The MCD spectrum of thiophene is only slightly perturbed by substituents, and this is also expected to be true of the quite similar MCD spectra of selenophene and tellurophene. These molecules can then be classified as “hard” chromophores. On the other hand, pyrrole and furan have different and much weaker MCD spectra which change shape considerably when substituents are introduced. The implications of these observations are further discussed.     

Reactions of methyl trifluoropyruvate with five-membered electron-rich heterocycles

A study was carried out on the reactions of methyl trifluoropyruvate with Nmethylpyrrole, furan, and thiophene. Conditions were found for the selective monoalkylation and dialkylation of these heterocycles. The sites of substitution of the heterocycle in the monoalkylation and dialkylation reactions were determined.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2369–2371, October, 1989.     

Phosphorylation of five-membered aromatic heterocycles with phosphorus tribromide

Phosphorus trichloride in a basic medium is a convenient reagent for the direct C-phosphorylation of electron-rich aromatic heterocycles. The compounds obtained can be used for the synthesis of various types of heteroaryl and diheteroaryl derivatives of tri- and pentavalent phosphorus. © 1995 John Wiley & Sons, Inc.     

Benzene fused five-membered heterocycles. A theoretical approach

The Nuclear Independent Chemical Shift of each ring, as a criterion of aromaticity, is used to explain the stability order of benzopyrrole, benzofuran and benzothiophene, and their isomers. The results indicate that the benzene ring is aromatic in all the systems. The five-membered rings of benzopyrrole, benzofuran and benzothiophene are also aromatic, whereas those of isobenzopyrrole, isobenzofuran and isobenzothiophene are non-aromatic. This could be an explanation of the stability of the former molecules. The molecular orbitals and the condensed Fukui functions derived from the electronic structure calculations are also reported. These reactivity indices explain the expected electrophilic substitution of these compounds. The theoretical structure, ionization energies, order of aromaticity, stability and reactivity are in good agreement with the experimental results. The usefulness of this approach to determine the reactivity is discussed since their stability and reactivity may be understood. The reactivity indices are useful to explain and confirm the experimental information, and for molecules with unknown reactive behavior, this approach could help to predict some of the reactions.     

五元氮杂环的开环反应研究进展

综述了近年来各种五元氮杂环的开环反应及其在有机合成中的应用。杂环化合物在有机合成中的作用越来越重要,五元氮杂环是其中最重要的一部分,其开环反应可以用来合成某些用其它方法难以合成的多官能团化合物,或通过开环和修饰合成其它环状化合物,还可以作为保护基以及研究仿生合成领域中各类复杂的生化反应等。     

Determination of substitution sites in monosubstituted five-membered aromatic heterocycles

Similar magnitudes of proton-proton couplings across three, four, and five bonds and proton-carbon couplings across two and three bonds combined with difficult to predict substituent effects make the results of an indiscriminate use of routine (COSY, HSQC, HMBC, etc.) techniques for substitution site determination in C-monosubstituted five-membered heteroaromatics suspect. As demonstrated on two examples of natural products, the use of 1,1-ADEQUATE leads to unambiguous substitution site determination lending thus further support to suggested inclusion of 1,1-ADEQUATE data into computer-assisted structure elucidation (CASE) protocols.     

Acid-base properties of five-membered nitrogen-containing heterocycles (review)

The acid-base properties of five-membered nitrogen-containing heterocycles with one, two, three, and four nitrogen atoms in the ring are discussed. The factors that determine the properties of these compounds as acids and bases are analyzed. The problems that arise in comparing the basicities of heterocycles, the protonation of which is described by different acidity scales are stressed. A significant amount of space is allotted to an examination of the acid-base properties of nitrogen-containing heterocycles in the gas phase and to the use of quantum-chemical methods in the study of the protolytic equilibria of these compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 579–592, May, 1988.     

Thermal transformation of cyclopropylazoarenes into the five-membered nitrogen-containing heterocycles

Cyclopropylazoarenes containing methoxy groups in the aromatic ring give the corresponding N-arylpyrazolines on the reflux in o-dichlorobenzene or on SnCl₂ catalysis at 80 °C in good yields. The products can be smoothly oxidized into the corresponding pyrazoles. Thermolysis of cyclopropylazoarenes containing hydroxy groups in the aromatic ring proceeds more complicated. Thus in the case of resorcin azo derivative, strong resinification of the reaction mixture is observed and the corresponding N-arylpyrazoline is isolated only in −40% yield. Under similar conditions, thermolysis of 1-cyclopropyl- and 1-(1-methylcyclopropyl)azo-2-naphthol proceeds otherwise and unexpectedly leads to naphtho[1,2-d]oxazole derivatives with degradation of the cyclopropane ring. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1686–1692, August, 2008.     

Isotopic hydrogen exchange in methyl derivatives of five-membered aromatic heterocycles

The kinetics of isotopic exchange of the hydrogen atoms of the methyl groups in an alcohol solution of potassium ethoxide were studied for an extensive series of methyl derivatives of azoles and di-, tri-, and tetrazoles. The electronic effect of one or several heteroatoms and substituents on the rate of deuterium exchange of five-membered heterocycles is satisfactorily conveyed by the correlation relationship previously established for a series of substituted toluenes and six-membered heteroaromatic compounds ( _25°=7.6). The limitations that exist in a number of cases are discussed in connection with the peculiarities of the electron-density distribution in five- and six-membered heterocycles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1196–1201, September, 1977.     

Deprotonative metalation of five-membered aromatic heterocycles using mixed lithium-zinc species

Deprotonation of benzoxazole, benzothiazole, benzo[b]thiophene, benzo[b]furan, N-Boc-protected indole and pyrrole, and N-phenylpyrazole using an in situ mixture of ZnCl(2).TMEDA (0.5 equiv) and lithium 2,2,6,6-tetramethylpiperidide (1.5 equiv) in THF at room temperature is described. The reaction was evidenced by trapping with iodine, regioselectively giving the expected functionalized derivatives in 52-73% yields. A mixture of mono- and disubstituted derivatives was obtained starting from thiazole. Cross-coupling reactions of 2-metalated benzo[b]thiophene and benzo[b]furan with heteroaromatic chlorides proved possible under palladium catalysis. A reaction pathway where the lithium amide and zinc diamide present in solution behave synergically was proposed for the deprotonation reaction, taking account of NMR and DFT studies carried out on the basic mixture.     

Phase transfer catalysis in the chemistry of five-membered nitrogen-containing heterocycles

The methods for synthesis and reactions of five-membered nitrogen-containing heterocycles under the conditions of phase transfer catalysis as well as the application of quaternized heterocycles as phase transfer catalysts are discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2115–2121, November, 1995.     

Rearrangements of cyclopropenes into five-membered aromatic heterocycles: mechanistic aspect

This review covers rearrangements of cyclopropenes into aromatic five-membered heterocyclic compounds, namely furans and pyrroles; accompanied by small ring cleavage proceeding in the presence of catalytic amounts of transition metals, Lewis acids, or under UV irradiation.