Localized molecular orbitals and chemical binding in five-membered heterocycles. II

The localized molecular orbitals (LMOs) of thiophene, furan, and pyrrole are derived from ab initio 4-31G wavefunctions using Boys' criteria for localization. From the transferability point of view, these LMOs are classified as (i) completely different and nontransferable LMOs (these are the lone-pair orbitals on O and N on one hand and those on S on the other hand), (ii) chemically similar lone pairs and inner shells on O and N (of furan and pyrrole, respectively), and (iii) chemically equivalent C? C, C?C, and C? H LMOs in the three heterocycles. The sp³ hybridization of the L core of sulfur, its appreciable polarization, and considerable involvement in bonding in the C? S bond region have been discussed. The present investigation indicates the limitation of the application of semiempirical MO methods to molecules that contain second-row atoms due to both the appreciable core—valence and π-σ interactions involving such atoms. Qualitative investigation of aromaticity and reactivity of the studied heterocycles agrees satisfactorily with experimental observations and shows that conclusions drawn based solely on static factor considerations (charge distribution in the noninteracting molecules) might very well be misleading and such factors determine the ease rather than the final orientation of the substituent.     

Effect of the heteroatom on the one-electron reduction of α-nitro derivatives of five-membered heterorings

The potentials of the first polarographic half waves of the electrical reduction in dimethylformamide (DMF) of -nitro derivatives of furan, thiophene, selenophene, and their analogs in the benzene series and the hfs constants of the EPR spectra of the electrochemically generated anion radicals of these compounds are presented. It was established that these parameters in the series of examined heterorings regularly follow the electron affinities of the heteroatoms in their s²p²pp valence state. The relative conductivity of the electronic effects of substituents is higher (1.08) in the level of the unpaired electron of the furan ring, while the conductivities in the thiophene (0.95) and selenophene (0.94) ring are lower, than in the case of the benzene ring. The conductivity through the heterorings in the molecular state is higher by a factor of 1.2 than in the level of the unpaired electron.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1606–1612, December, 1980     

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.     

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.     

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.     

Reaction of amino substituted heterocycles with one heteroatom in a five-membered ring as enamines. A revision

2-Aminoheterocycles (pyrrole, furan, and thiophene) exist in solution in the amino form of type 1 and 5 . They undergo protonation at the exocyclic nitrogen in DMSO/TFA and protonation at position 5 in TFA. However when the electrophile is different from proton the 2-aminoheterocyles do not react as enamines (C-acylation is never observed), but their behavior is typical of aromatic amines, giving rise to N-acylated product of type 9 .     

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.     

On a definition of bond energies based on localized molecular orbitals

A theoretical model is presented for defining bond energies based on localized molecular Orbitals. These bond energies are obtained by rearranging the total SCF energy including the nuclear repulsion term to a sum over orbital and orbital interaction terms and then to total orbital terms, which can be interpreted as the energies of localized orbitals in a molecule. A scaling procedure is used to obtain a direct connection with experimental bond dissociation energies. Two scale parameters are employed, the C-C and the C-H bond dissociation energy in C₂H₆ for A-B and C-H type bonds, respectively. The implications of this scaling procedure are discussed. Numerical applications to a number of organic molecules containing no conjugated bonds gives in general a very satisfactory agreement between experimental and theoretical bond energies.     

Substitution in a number of five-membered heterocycles with one heteroatom catalytic alkylation of N-methylpyrrole and thiophene with olefins

It has been found that a decrease in the yield of -substituted products during alkylation with olefins is observed in a number of five-membered heterocycles (furan, thiophene, and N-methylpyrrole). The change in the -orienting effect depends not only on the nature of the heteroatom but also on the type of reaction and on the conditions of the process. In the case of N-methylpyrrole, the possibility of C-alkylation of the pyrrole ring with olefins was demonstrated for the first time.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 502–506, April, 1973.     

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 functionalized derivatives of mono- and diphosphonic acids substituted with five-membered nitrogen heterocycles

New types of (hydroxymethyl)phosphonic and (methylene)diphosphonic acids bearing heterocyclic fragments were synthesized by addition of tris(trimethylsilyl) phosphite to N-formyl derivatives of five-membered nitrogen heterocycles.     

Inversion of the highest occupied molecular orbitals of imidazole derivatives

Conclusions Photoelectron spectroscopy data and quantum chemical calculations for imidazoles and their benzologs indicate that the fusion of the five-membered heterocycle with a benzene ring leads to the inversion of the highest occupied molecular orbitals.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2591–2595, November, 1987.     

The tautomerism of hydroxy derivatives of five-membered oxygen,nitrogen, and sulfur heterocycles

The unstable enolic tautomers 3-hydroxyfuran, 2- and 3-hydroxythiophene, 3-hydroxy-pyrrole, 3-hydroxy-1-methyl-pyrrole and their benzo-derivatives have been generated in solution and the rate and equilibrium constants for their ketoization determined.     

σ Derivatives of cyclopentadienyldicarbonyliron with five-membered heterocycles

Russian Chemical Bulletin -     

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.     

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.     

Correlation of the molecular orbitals of organic sulfides (selenides) and five-membered heterocyclic compounds by photoelectron spectroscopy

The structure and the correlation of the molecular orbitals were studied for divinyl chalcogenides and the isoelectronic five-membered heterocyclic compounds by photoelectron spectroscopy (PES). It was shown that the two frontier orbitals are inverted in the transition from divinyl sulfide to thiophene, while the heterocyclization of divinyl selenide is accompanied by quasidegeneration. According to PES, the orbital structure of the alkyl vinyl chalcogenides does not depend on the nature of the heteroatom (S, Se) or on the structure of the alkyl radical: ₂ < ₁ < ₂ < ₂. Linear correlations were obtained between the energies of the ₁ and ₂ MOs of the investigated groups of compounds, i.e., one for the vinyl Sulfides (selenides) and thiophenes (selenophenes) and another for the saturated derivatives of sulfur and selenium. The correlations in the compounds of the various chalcogens do not coincide, although they are similar.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2317–2324, October, 1991.