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.     

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.     

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.     

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.     

Structural elucidation of nitro-substituted five-membered aromatic heterocycles utilizing GIAO DFT calculations

The GIAO (Gauge Including Atomic Orbitals) DFT (Density Functional Theory) method is applied at the B3LYP/6-31+G(d,p)//B3LYP/6-31+G(d), B3LYP/6-311++G(d,p)//B3LYP/6-31+G(d), B3LYP/6-311+G (2d,p)//B3LYP/6-31+G(d) and B3LYP/6-311++G(d,p)//B3LYP/6-311++G(d,p) levels of theory for the calculation of proton and carbon chemicals shifts and coupling constants for 25 nitro-substituted five-membered heterocycles. Difference (1D NOE) spectra in combination with long-range gHMBC experiments were used as tools for the structural elucidation of nitro-substituted five-membered heterocycles. The assigned NMR data (chemical shifts and coupling constants) for all compounds were found to be in good agreement with theoretical calculations using the GIAO DFT method. The magnitudes of one-bond (1JCH) and long-range (nJCH, n>1) coupling constants were utilized for unambiguous differentiation between regioisomers of nitro-substituted five-membered heterocycles.     

Ozonolysis of five-membered heterocycles

The relative reaction rate of five-membered heterocycles with ozone was evaluated. These relative rates were correlated to the highest bond order value in the corresponding ring, calculated by the convenient HMO method. From this correlation, the reactivity of heterocycles with ozone was able to be predicted. Also it was concluded that the predominant product in the ozonolysis of five-membered heterocycles containing an oxygen atom was the corresponding carboxylic acid, while nitrogen heterocycles gave the corresponding amide.     

NMR spectra, GIAO and charge density calculations of five-membered aromatic heterocycles

The B3LYP/6-31+G(d) molecular geometry optimized structures of 17 five-membered heterocycles were employed together with the gauge including atomic orbitals (GIAO) density functional theory (DFT) method at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p) and B3LYP/6-311+G(2d,p) levels of theory for the calculation of proton and carbon chemicals shifts and coupling constants. The method of geometry optimization for pyrrole (1), N-methylpyrrole (2) and thiophene (7) using the larger 6-311++G(d,p) basis sets at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p), B3LYP/6-31+G(2d,p) and B3LYP/cc-pVTZ levels of theory gave little difference between calculated and experimental values of coupling constants. In general, the (1)H and 13C chemical shifts for all compounds are in good agreement with theoretical calculations using the smaller 6-31 basis set. The values of nJHH(n=3, 4, 5) and rmnJ(CH)(n=1, 2, 3, 4) were predicted well using the larger 6-31+G(d,p) and 6-311++G(d,p) basis sets and at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p), B3LYP/6-31+G(2d,2p) levels of theory. The computed atomic charges [Mülliken; Natural Bond Orbital Analysis (NBO); Merz-Kollman (MK); CHELP and CHELPG] for the B3LYP/6-311++G(d,p) geometry optimized structures of 1-17 were used to explore correlations with the experimental proton and carbon chemical shifts.     

Quantum-chemical investigation of the 1,2-proton shift in protonated five-membered aromatic heterocycles

Calculations of the energetics of the 1,2-proton shift in protonated five-membered aromatic heterocycles — pyrrole, furan, and thiophene — have been carried out by the SCF MO LCAO method in the MINDO/3 approximation and nonempirically on the OST-3GF (OST-3GF*) basis. The general features of this process, and also the influence of solvation and of taking into account the vacant d-AOs of the sulfur atom in the protonated form of thiophene on the results of the calculation are considered. The results obtained have been used for a discussion of the activity and selectivity of the heterocycles considered in aromatic electrophilic substitution reactions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1186–1190, September, 1984.     

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.     

σ Derivatives of cyclopentadienyldicarbonyliron with five-membered heterocycles

Russian Chemical Bulletin -     

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.     

Synthesis,insecticidal activity and stability study of novel nitromethylene neonicotinoids with five-membered aromatic heterocycles

Twenty-four novel neonicotinoid analogues with nitromethylene and five-membered aromatic heterocycles were designed and synthesized. All target molecular structures have been confirmed by analytical and spectral data. Some compounds exhibited notable insecticidal activities against aphid (Aphis medicaginis) and brown planthopper (Nilaparvata lugens). The aqueous stability test confirmed that the stabilities of those compounds were superior to the leading compound, and the photostability was even better than that of imidacloprid.     

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.     

Synthetic approaches to unsaturated five-membered heterocycles containing both ring and side-chain phosphorus atoms

The syntheses of several structurally interesting 2-diphenylphosphinyl-substituted 2-phospholenes and phospholanes are reported together with a discussion of the ₃₁P and 13° C nmr spectral properties of these compounds. Several of these syntheses were found to be highly stereoselective and the potential of some of the products of these reactions as precursors to phosphole derivatives bearing phosphorus-containing side-chains has also been explored. A new, and possibly general, route to 4-oxo-2-phospholene oxides or sulfides from the corresponding 4-methylene compounds is also reported. This route involves an unusual free-radical catalyzed oxidative cleavage of the 4-methylene group by molecular oxygen and a probable mechanism for this reaction is proposed.     

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.     

Electrophilic behavior of the pi delocalized azepinium ion: Friedel-Crafts reactions with benzenes and five-membered aromatic heterocycles

[reaction: see text] Although the reactivity of tropylium ion with aromatic substrates is low, the reaction of azepinium ion with aromatic substrates such as benzene, phenol, furan, and thiophene resulted in the formation of 2-aryl-2H-azepine as a major product. An exceptional result in the formation of ring-contracted product was observed in the reaction with pyrrole.