Gold and silver assisted synthesis of five-membered oxygen and nitrogen containing heterocycles

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 the present review is to focus on the applications of gold- and silver-catalytic systems for the synthesis of five-membered oxygen- and nitrogen-heterocycles.     

Experimental and theoretical investigation of new furan and thiophene derivatives containing oxazole,isoxazole, or isothiazole subunits

Structural Chemistry - Herein, we present joint experimental and theoretical studies on newly designed thiophene- or furan-based oxazole, isoxazole, and isothiazole derivatives. Our synthetic...     

Synthesis and NMR studies of 2- and 3-fluorosubstitued five-membered heterocycles

A set of 2-fluoro- and 3-fluoro-substituted thiophenes, pyrroles and furans has been synthesized by a treatment of the corresponding lithio derivatives with N-fluorodibenzenesulfonamide. For all these compounds, and coupling constants and NMR chemical shifts have been measured. In all cases, a dramatic increase of the couplings has been observed in 2-fluoro- and 3-fluoro-substituted compounds in comparison with those measured for the parent compounds. The same is valid for measured in 3-fluoro derivatives.The DFT calculations performed for 2- and 3-fluoro-substituted compounds reproduce very well the experimental coupling values and show that the Fermi contact contribution is the main factor determining their magnitude. Also the trends observed in the NMR shieldings are well reflected in the calculated DFT data.     

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.     

Quantum chemical study of the structure and thermochemistry of the five-membered nitrogen-containing heterocycles and their anions and radicals

The nitrogen-containing heterocycles are of interest as high-energy-density materials for use as propellants and explosives, while the pyrolysis of these compounds is also important in understanding the evolution of unwanted NO and NO2 (NOx) from organic fuels such as coal and biomass. We have used ab initio and density functional methods to study the molecular structures and thermochemical properties of the five-membered nitrogen-containing heterocycles and their anions and radicals corresponding to respective heterolytic and homolytic loss of a hydrogen atom from either a nitrogen or carbon site. Many of these thermochemical properties have not previously been measured, especially for the heterocycles containing three and four nitrogen atoms. Using the theoretical methods CBS-APNO, G3, and G3B3, we calculate enthalpies of formation of 26.5, 42.4, 31.9, 63.7, 46.8, 81.0, and 79.0 kcal mol-1 for pyrrole, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, 1H-tetrazole, and 2H-tetrazole. A correlation is developed between the number of nitrogen atoms in a heterocycle and its enthalpy, and we extrapolate this relationship to predict the enthalpy of formation of pentazole. N-H BDEs in the heterocycles typically increase with the number of nitrogen atoms in the molecule, while C-H BDEs are similar in all of the studied heterocycles, at around 120 kcal mol-1. In all cases the N-H BDEs are weaker than the C-H BDEs, suggesting abstraction of the N-H hydrogen atom is more likely. Deprotonation enthalpies and free energies reveal that the N-H protons become more acidic with increasing number of nitrogen atoms in the heterocycle. C-H protons are less acidic than N-H protons by ca. 49 kcal mol-1, or ca. 35 kcal mol-1 when adjacent to the NH group. Trends in N-H and C-H acidities can be qualitatively explained by electrostatic effects and electron affinities. From its use as a reference species in our calculations, we identify that the experimental enthalpy of pyrimidine (1,3-diazine) may be in error by ca. 1-3 kcal mol-1, and we recommend an enthalpy of formation of 44.8 +/- 1.0 kcal mol-1.     

Theoretical investigation of photoelectron spectra of furan,pyrrole, thiophene,and selenole

The ionization spectra of furan, pyrrole, thiophene, and selenophene have been calculated within the framework of the nonempirical quantum-chemical method with the Green's one-particle function in the approximation of the third order algebraic diagram construction [ADC(3)]. The calculated energies and the intensity of vertical transitions pertaining to the ionization of outer and inner shells are compared with the newest experimental data. The good agreement of theoretical and experimental results enabled a detailed assignment and interpretation of the observed photoelectron spectra to be carried out. Problems of disturbing the picture of orbital ionization are considered; the mechanism of formation of low-lying photoelectron satellites is explained. Certain general rules and trends of the behavior of the spectra of the systems studied are considered. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70^th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1366–1379. September, 2008.     

Solvent-assisted intramolecular proton transfer in thiopurinol: application of M06-2X functional

All available conformers of tisopurine as an important pharmaceutical molecule are optimized and frequency calculations calculated at M06-2X/6-311++G(2d,2p) level of theory. These conformers are classified in 22 different tautomers, tautomer Z showing the most stable tautomer in the gas phase. Effects of four different solvents on the most stable conformer of each tautomer is calculated. Solvents cause stabilization of all conformers and relative solvent stabilization is as follows: water > DMSO > acetone > toluene. Energy profile for such stabilization is illustrated and mechanism of proton transfer studied at the same level of theory. Solvent-assisted proton transfer performed when water and methanol used as solvents. Results indicate that explicit solvent effect has much more stabilization on tautomerization processes compared to implicit solvent effect.     

An ab initio investigation of the Buckingham birefringence of furan, thiophene, and selenophene in cyclohexane solution

Using a recently developed quadratic response methodology for the calculation of frequency-dependent third-order properties of molecules in solution, we investigate the Buckingham birefringence of furan, thiophene, and selenophene in cyclohexane solution. These systems are chosen since accurate experimental data are available, allowing for a direct comparison of experimental observations with our theoretical estimates. Our model for describing the solvent effects is based on a dielectric continuum approach for the solvent, and uses a molecule-shaped cavity. Our results show qualitatively different Buckingham constants and effective quadrupole centers calculated with and without the solvent, and only when the solvent is included are the qualitative trends observed experimentally reproduced. It is demonstrated that a significant part of this effect arises from the geometry relaxation of the molecules in the solvent.     

Unrestricted Hartree-Fock calculations of spin density distributions in the radical anions of some heterocycles derived from thiophene,furan and pyrrole

Spin density distributions in the radial anions of some heterocycles derived from thiophene, furan and pyrrole have been obtained using the unrestricted Hartree-Fock method. Good agreement between the calculated results and experimental data has been observed.     

Synthesis and second-order nonlinear optical properties of new chromophores containing benzimidazole, thiophene, and pyrrole heterocycles

A new series of thermally stable benzimidazole-based nonlinear optical (NLO) chromophores 4 and 5 have been developed. These chromophores possess a thienylpyrrolyl π-conjugated system attached to functionalized benzimidazole heterocycles. This feature leads to robust chromophores with excellent solvatochromic properties, high thermal stabilities and good molecular optical nonlinearities.     

Improved preparation of racemic 2-amino-3-(heteroaryl)propanoic acids and related compounds containing a furan or thiophene nucleus

Racemic 2-amino-3-(heteroaryl)propanoic acids (1), mostly with a furan or thiophene nucleus as a heteroaryl group, were synthesized in 48-94% yield by the reduction of 3-(heteroaryl)-2-(hydroxyimino)propanoic acids (5) with zinc dust and formic acid in the presence of a catalytic amount of iron dust at 60 degrees C for 2 h. Under these conditions, unfavorable hydrogenolysis of bromine on the thiophene nucleus does not occur. Traditional N-formylation of the prepared 3-(heteroaryl)alanine (1) with a mixture of formic acid and acetic anhydride afforded 2-(formylamino)-3-(heteroaryl)propanoic acids (6) in 51-95% yield.     

Dissolution thermochemistry of alkali metal dianion salts (M2X1, M = Li+, Na+, and K+ with X = CO3(2-), SO4(2-), C8H8(2-), and B12H12(2-))

The dissolution Gibbs free energies (ΔG°(diss)) of salts (M(2)X(1)) have been calculated by density functional theory (DFT) with Conductor-like Polarizable Continuum Model (CPCM) solvation modeling. The absolute solvation free energies of the alkali metal cations (ΔG(solv)(M(+))) come from the literature, which coincide well with half reduction potential versus SHE data. For solvation free energies of dianions (ΔG(solv)(X(2-))), four different DFT functionals (B3LYP, PBE, BVP86, and M05-2X) were applied with three different sets of atomic radii (UFF, UAKS, and Pauling). Lattice free energies (ΔG(latt)) of salts were determined by three different approaches: (1) volumetric, (2) a cohesive Gibbs free energy (ΔG(coh)) plus gaseous dissociation free energy (ΔG(gas)), and (3) the Born-Haber cycle. The G4 level of theory, electron propagator theory, and stabilization by dielectric medium were used to calculate the second electron affinity to form the dianions CO(3)(2-) and SO(4)(2-). Only the M05-2X/Pauling combination with the three different methods for estimating ΔG(latt) yields the expected negative dissolution free energies (ΔG°(diss)) of M(2)SO(4). Salts with large dianions like M(2)C(8)H(8) and M(2)B(12)H(12) reveal the limitation of using static radii in the volumetric estimation of lattice energies. The value of ΔE(coh) was very dependent on the DFT functional used.     

Absorption and Emission Spectra of p-Phenylbenzoyl Methanthiol: Methanol Effect Based on M06-2X Calculations

The absorption and emission spectra, as well as the photolysis mechanism of p-phenylbenzoyl methanthiol in methanol and in gas phase were elucidated in detail based on the molecular structures of the ground states, excited states and their spectroscopic characters. The TD-M062 X calculations demonstrate that the S_1 state in gas phase will decompose into SH and p-phenylbenzoyl radical via a barrierless process, but the T_1 and T_2 do not photolyze. By adding 1 and 2 methanol molecules onto p-phenylbenzoyl methanthiol, the CPCM model can perfectly describe the solvation effects of methanol. Methanol may stabilize the excitation states, but also protects the resulting radical products from recombination.     

Investigations on stabilities and intermolecular interactions of different naphthalene derivatives dimers by using B3LYP and M06-2X density functional calculations

In this paper, the stabilities and hydrogen bond interactions of 4-chloro-1-naphthol, 1-hydrox-ynaphthalene and 1,4-dihydroxynaphthalene dimers have been theoretically investigated by means of study on binding energies with nonlocal hybrid three-parameter Lee-Yang-Parr, B3LYP, and M06-class functional calculations. Calculations on dimers aim to provide as a test of the efficacy of M06 calculations for intermolecular interaction calculations and more strongly bound systems. For hydroxyl- and halo-substituted derivatives of naphthalene, total electronic energies, their correction for the zero point vibrational energies with some calculated thermodynamic properties and their relative differences are together in order to discuss the rotamer structures. Static (hyper) polarizabilities and the electric dipole moments, frontier molecular orbital energy gaps and the relationships between them have been interpreted. Generally, they are seen that the calculated geometric parameters and spectral results were in a good agreement with the corresponding experimental data.     

Study on the antioxidant activity and quantification of thioamides based on nitrogen five-membered heterocycles by the kinetic technique

The antioxidant activity of heterocyclic thioamides based on imidazole, triazole, tetrazole, thiazole, thiazoline, and thiadiazole is estimated by spectrophotometry using the rate constant of reaction with the chromogenic radical 2,2′-diphenyl-1-picrylhydrazyl. The rate constant of direct transfer of a hydrogen atom to the radical in carbon tetrachloride is maximal for 1-methylimidazoline-2-thione. The protective antioxidant effect of the preparations in ethanol falls down abruptly from 4-phenylthiazoline-2-thione (k = 1.06 × 10⁴ M⁻¹min⁻¹) to the thioamides based on triazole and thiazoline (k ∼ 20 M⁻¹min⁻¹). In acetonitrile, thiazole derivatives show the most substantial antioxidant activity, k = n ×10⁴ M⁻¹min⁻¹, which goes down to zero if the aromaticity of the heterocycle is broken. As established, for the pseudo first order reaction between thioamides and the chromogenic radical, the reaction rate linearly depends on the concentration of thioamides. A spectrophotometry kinetic method for the quantification of heteroaromatic thioamides is elaborated.     

Quantum-chemical interpretation of the mass spectra of pyrrole,furan, and thiophene

A simple quantum-chemical interpretation of the mass-spectrometric fragmentation of organic molecules in which the probability of the cleavage of the bonds under the influence of electron impact is related to their self-consistent -electron orders and the possible rearrangement processes are described on the basis of the long-range bond orders is proposed. This approach was tested in the case of pyrrole, furan, and thiophene.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 620–624, May, 1987.     

Angular distributions in the photoelectron spectroscopy of furan,thiophene, and pyrrole

The photoelectron angular distributions of furan, thiophene, and pyrrole are reported. The trends in the value of the asymmetry parameter β and in the shapes and positions of bands in the spectra are used to assign the peaks that correspond to ionization from the π orbitals in these molecules.     

Quantum-chemical investigation of the electrophile affinity of molecules of five-membered heterocycles with one hetero-atom and some model systems

Quantum-chemical calculations have been made of the energy characteristics of the molecules of pyrrole, furan, thiophene, and selenophene, the simplest derivatives of N, O, S, and Se with sp³-and sp²-hybridized C atoms and heteroatoms, and also of the products of addition of proton and certain other electrophiles to these molecules. The calculations were carried out by HF, B3LYP, and MP2 methods with the 6−31+G(d) basis set with corrections to the energy of zero-point vibrations. It was shown that the values of the affinity of the nitrogen-containing systems towards the electrophile were significantly greater than for their analogs, derivatives of chalcogens, while the relative stability of the onium states of the latter depends both on the hybridization of the heteroatoms, and also on the nature of the electrophile. Analysis of the obtained results made it possible to build a stability series of the onium compounds and to interpret the special features of the positional selectivity in electrophilic substitution reactions of five-membered heteroaromatic compounds with one heteroatom. Dedicated to the remarkable heterocyclic chemist Aleksandr Fedorovich Pozharskii on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1645–1654, November, 2008.     

Unsaturated five-membered selenium-silicon containing heterocycles based on the reactions of selenium di- and tetrahalides with diorganyl diethynyl silanes

Reactions of SeBr₂ and SeCl₂ with diorganyl diethynyl silanes RR¹Si(CCH)₂ in CHCl₃ at room temperature result in regio- and stereoselective formation of a new class of unsaturated five-membered heterocycles, 4,4-R,R¹-3,6-dichloro(dibromo)-1,4-selenasilafulvenes (Z-isomers predominately), in preparative yields. Under similar conditions the reaction of SeBr₄ and SeCl₄ with diorganyl diethynyl silanes RR¹Si(CCH)₂ proceeds regioselectively to afford another new class of unsaturated five-membered heterocycles, 2-dichloro(dibromo)-methyl-2,4-dichloro(dibromo)-3,3-diorganyl-1-selena-3-silacyclopentenes-4. The structures of the heterocycles were proved by multinuclear (¹H, ¹³C, ²⁹Si, ⁷⁷Se) NMR spectroscopy, 2D NOESY NMR spectroscopy and mass-spectrometry. A long-range spin-spin interaction of protons through five bonds lacking in E-isomers was revealed in Z-isomers of fulvene-type heterocycles. In the MS spectra heterocycles of cyclopentene structure were shown to manifest themselves as fragmentary ions [M−HX]⁺ or [M−X]⁺.