Comparison of computational methods applied to oxazole,thiazole, and other heterocyclic compounds

A variety of computational methods, including the semiempirical techniques AM1, PM3, and MNDO, and the thermochemical basis sets of Benson and Stine, was used to calculate and compare heats of formation (ΔH_f°) data for optimized geometries of a variety of aromatic and nonaromatic heterocycles. Detailed analyses, including 6-31G* and MP2/6-31G* ab initio calculations, were performed for the oxazole and thiazole heterocycles. The results indicate a scatter among the methods sensitive to the nature of the heterocycle. This was in particular evident in the oxazole molecule, where AM1 gave a singularly high value of ΔH_f° consistent with longer calculated bond lengths, particularly about the oxygen atom. Aromatic stabilization energy appears to be addressed differently among the employed methods. Implications of this contrast applied to calculation of macromolecular systems containing heterocyclic units are discussed.     

Vacuum-ultraviolet ionization spectroscopy of the jet-cooled RNA-base uracil

Adiabatic ionization potential (9.3411 +/- 0.0008 eV) and cationic vibrational structure of the jet-cooled RNA-base uracil are both accurately and precisely determined for the first time using a vacuum-ultraviolet mass-analyzed threshold ionization spectroscopy.     

Synthesis of thiazole,oxazole and heterocyclic ring‐substituted 1,2‐dioxanes

The reactions of 4‐bromoacetyl‐3‐methoxy‐3‐methyl‐6,6‐diphenyl‐1,2‐dioxane with thioureas or thioamides gave 3‐methoxy‐3‐methyl‐6,6‐diphenyl‐4‐(4‐thiazolyl)‐1,2‐dioxanes in 63–90% yields. The similar reaction of 4‐bromoacetyl‐3‐methoxy‐3‐methyl‐6,6‐diphenyl‐1,2‐dioxane with acetamide gave 3‐methoxy‐3‐methyl‐4‐(2‐methyl‐4‐oxazolyl)‐6,6‐diphenyl‐1,2‐dioxane in 39% yields. The reactions of 4‐bromoacetyl‐3‐methoxy‐3‐methyl‐6,6‐diphenyl‐1,2‐dioxane with 3‐alkyl‐4‐amino‐5‐mercaptot[1,2,4]triazoles yielded 3‐methoxy‐3‐methyl‐6,6‐diphenyl‐4‐[3‐(5‐alkyl[1,2,4]triazolo[3,4‐b]‐2,3‐dihydro‐6H‐[1,3,4]thiadiazinyl)]‐1,2‐dioxanes in moderate yields (43–46%).     

Synthesis of sansalvamide A peptidomimetics: triazole, oxazole, thiazole, and pseudoproline containing compounds

Peptidomimetic-based macrocycles typically have improved pharmacokinetic properties over those observed with peptide analogs. Described are the syntheses of 13 peptidomimetic derivatives that are based on active Sansalvamide A structures, where these analogs incorporate heterocycles (triazoles, oxazoles, thiazoles, or pseudoprolines) along the macrocyclic backbone. The syntheses of these derivatives employ several approaches that can be applied to convert a macrocyclic peptide into its peptidomimetic counterpart. These approaches include peptide modifications to generate the alkyne and azide for click chemistry, a serine conversion into an oxazole, a Hantzsch reaction to generate the thiazole, and protected threonine to generate the pseudoproline derivatives. Furthermore, we show that two different peptidomimetic moieties, triazoles and thiazoles, can be incorporated into the macrocyclic backbone without reducing cytotoxicity: triazole and thiazole.     

Ionization spectroscopy of a DNA base: vacuum-ultraviolet mass-analyzed threshold ionization spectroscopy of jet-cooled thymine

The high-resolution ionization spectroscopy of DNA bases is reported for the first time. Vacuum-UV mass-analyzed threshold ionization (VUV-MATI) spectrum of jet-cooled thymine provides not only the most precise ionization potential but also its vibrational structure in the ground cationic state.     

Resonant two-photon ionization spectroscopy of jet-cooled OsN: 520-418 nm

The optical transitions of supersonically cooled OsN have been investigated in the range from 19,200 to 23,900 cm(-1) using resonant two-photon ionization spectroscopy. More than 20 vibronic bands were observed, 17 of which were rotationally resolved and analyzed. The ground state is confirmed to be (2)Δ(5/2), deriving from the 1σ(2) 2σ(2) 1π(4) 1δ(3) 3σ(2) electronic configuration. The X (2)Δ(5/2) ground state rotational constant for (192)Os(14)N was found to be B(0) = 0.491921(34) cm(-1), giving r(0) = 1.62042(6) ? (1σ error limits). The observed bands were grouped into three band systems with Ω' = 7/2 and four with Ω' = 3/2, corresponding to the three (2)Φ(7/2) and four (2)Π(3/2) states expected from the 1σ(2) 2σ(2) 1π(4) 1δ(3) 3σ(1) 2π(1) and 1σ(2) 2σ(2) 1π(4) 1δ(2) 3σ(2) 2π(1) electronic configurations. In addition, two interacting upper states with Ω' = 5/2 were observed, one of which is thought to correspond to a 1σ(2) 2σ(2) 1π(3) 1δ(3) 3σ(2) 2π(1), (2)Δ(5/2) state. Spectroscopic constants are reported for all of the observed states, and comparisons to related molecules are made. The ionization energy of OsN is estimated as IE(OsN) = 8.80 ± 0.06 eV.     

Two-color resonantly enhanced multiphoton ionization and zero-kinetic-energy photoelectron spectroscopy of jet-cooled indan

We report studies of supersonically cooled indan using two-color resonantly enhanced multiphoton ionization and two-color zero-kinetic-energy photoelectron spectroscopy. With the aid of ab initio and density-functional calculations, vibrational modes of the first electronically excited state of the neutral species and those of the cation have been assigned, and the adiabatic ionization energy has been determined to be 68458 +/- 5 cm(-1). Similar to the ground state and the first electronically excited state of the neutral molecule, the ground state of the cation is also proven to be nonplanar, with an estimated barrier of 213 cm(-1) and a puckering angle of 15.0 degrees. These conclusions will be discussed in comparison with a previous study of an indan derivative 1,3-benzodioxole.     

Convenient method for introduction of cyano group into nitrogen,sulfur, and oxygen heterocyclic compounds

A number of heterocyclic aldehydes were transformed via their NN-dimethythydrazones to nitriles in high yields using a one-pot procedure.Department of Organic Chemistry, Slovak Technical University, Bratislava, Slovakia. Institute of Organic Chemistry. Technical University, Wroclaw, Poland. Published in Khimiya Geterotsiklicheskikh Soedinerui, No. 10, pp. 1356–1357, October, 1995. Original article submitted August 24, 1995.     

Resonantly enhanced two photon ionization and zero kinetic energy spectroscopy of jet-cooled 4-aminopyridine

We report studies of supersonically cooled 4-aminopyridine (4-AP) using two-color resonantly enhanced multiphoton ionization (REMPI) and two-color zero kinetic energy (ZEKE) photoelectron spectroscopy. With the aid of ab initio and density functional calculations, vibrational modes of the first electronically excited state (S1) of the neutral species and those of the cation have been assigned, and the adiabatic ionization potential has been determined to be 62291+/-6 cm(-1). The REMPI spectrum of the S1 state is dominated by ring deformation modes and the inversion mode of the amino group, while the ZEKE spectra demonstrate a strong propensity of Deltav=0, where v is the vibrational quantum number of the intermediate vibronic state from S1. In addition, the ZEKE spectra obtained via different vibrational levels of the S1 state contain four common features, corresponding to the activation of four different vibrational modes of the cation. These observations are explained in terms of the structural changes from the ground state to S1 and further to the cation. The vibrational mode distributions in both the REMPI and the ZEKE spectra, the excitation energy of the S1 state, and the ionization potential of 4-AP, are remarkably similar to those of aniline, suggesting that the electronic activity is centered on the ring.     

Researches on compounds with oxygen in the heterocyclic ring

Alkylation of furan and sylvan with 2-phenyl-2-chloropropane and cinnamyl chloride, and alkylation of sylvan with tert-butyl chloride in the presence of zinc chloride and zinc acetate are described.For Part IV see [1].     

X-ray emission spectroscopy and the electronic structure of heterocyclic compounds

The electronic structure of the pyridine molecule has been investigated by x-ray emission spectroscopy. The NK _y and CK _y emission spectra have been measured. Ab initio and MNDO calculations have been carried out and individual bands in the spectra have been identified subsequently. The calculations produce spectral contours which approximate those of the experimental spectra.For Communication 3 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1484–1487, November, 1993.     

Laser induced fluorescence and resonant two-photon ionization spectroscopy of jet-cooled 1-hydroxy-9,10-anthraquinone

We carried out laser induced fluorescence and resonance enhanced two-color two-photon ionization spectroscopy of jet-cooled 1-hydroxy-9,10-anthraquinone (1-HAQ). The 0-0 band transition to the lowest electronically excited state was found to be at 461.98 nm (21,646 cm(-1)). A well-resolved vibronic structure was observed up to 1100 cm(-1) above the 0-0 band, followed by a rather broad absorption band in the higher frequency region. Dispersed fluorescence spectra were also obtained. Single vibronic level emissions from the 0-0 band showed Stokes-shifted emission spectra. The peak at 2940 cm(-1) to the red of the origin in the emission spectra was assigned as the OH stretching vibration in the ground state, whose combination bands with the C=O bending and stretching vibrations were also seen in the emission spectra. In contrast to the excitation spectrum, no significant vibronic activity was found for low frequency fundamental vibrations of the ground state in the emission spectrum. The spectral features of the fluorescence excitation and emission spectra indicate that a significant change takes place in the intramolecular hydrogen bonding structure upon transition to the excited state, such as often seen in the excited state proton (or hydrogen) transfer. We suggest that the electronically excited state of interest has a double minimum potential of the 9,10-quinone and the 1,10-quinone forms, the latter of which, the proton-transferred form of 1-HAQ, is lower in energy. On the other hand, ab initio calculations at the B3LYP/6-31G(d,p) level predicted that the electronic ground state has a single minimum potential distorted along the reaction coordinate of tautomerization. The 9,10-quinone form of 1-HAQ is the lowest energy structure in the ground state, with the 1,10-quinone form lying approximately 5000 cm(-1) above it. The intramolecular hydrogen bond of the 9,10-quinone was found to be unusually strong, with an estimated bond energy of approximately 13 kcal/mol (approximately 4500 cm(-1)), probably due to the resonance-assisted nature of the hydrogen bonding involved.     

One-photon mass-analyzed threshold ionization spectroscopy of 1,3,5-trifluorobenzene: the Jahn-Teller effect and vibrational analysis for the molecular cation in the ground electronic state

One-photon mass-analyzed threshold ionization spectrum of 1,3,5-trifluorobenzene was obtained by using vacuum ultraviolet radiation generated by four-wave difference frequency mixing in Kr. The Jahn-Teller parameters for the e' modes (nu(8)-nu(14)) of 1,3,5-C(6)H(3)F(3)(+) in the ground electronic state needed for spectral analysis were taken from the density functional theory results initially and were upgraded through fits to the experimental results. Excellent agreement was achieved between the experimental and calculated Jahn-Teller energy levels. Assignments of the Jahn-Teller inactive modes were accomplished by referring to the calculated frequencies and the selection rule. The ionization energy of 1,3,5-trifluorobenzene determined from the position of the 0-0 band was 9.6359+/-0.0006 eV.     

Thermodynamic analysis of strain in the five-membered oxygen and nitrogen heterocyclic compounds

Cyclopentane is conventionally strained. Replacement of a carbon atom by a heteroatom obviously impacts angular strain in the five-membered ring compounds. Changes of strains in the five-membered cycles are also caused by a double bond or atttached benzene rings. We studied the thermochemical properties of Indane, 2,3-dihydrobenzofuran, indoline, N-methyl-indoline, carbazole, and N-ethyl-carbazole to obtain a better quantitative understanding of the energetics associated with these compounds containing five-membered ring units. We used combustion calorimetry, transpiration method, and high-level first-principles calculations to derive gaseous enthalpies of formation of the five-membered heterocyclic compounds. Our new values together with the selected values for parent heterocyclic compounds, available from the literature, were used for calculation of the strain energies H(S) of five-membered C-, N-, and O-containing cycles. Quantitative analysis of the resulting stabilization or destabilization of a molecule due to interaction of benzene rings with the heteroatom has been performed.     

The anti-HIV potential of imidazole,oxazole and thiazole hybrids: A mini-review

Human immunodeficiency virus (HIV) especially HIV-1 infection and its progression to acquired immune deficiency syndrome (AIDS) remains a significant global health challenge. The advent of the highly active antiretroviral therapy (HAART) has greatly extended the life expectancy of patients living with HIV, but it has become evident that long-term HAART will not eliminate the HIV reservoir and cure the infection. Moreover, the drug resistance and undesirable side effects hamper efficacious therapy, creating an urgent need to develop novel, more effective and less toxic anti-HIV therapeutics. Imidazole, oxazole and thiazole with two heteroatoms at meta-position of five-membered rings are fascinating structures and constitute an important class of heterocycles in drug discovery. Their derivatives could exert the anti-HIV activity through diverse mechanisms and possess promising antiviral activity against both drug-sensitive and drug-resistant HIV strains. This review summarizes the research progress made regarding the anti-HIV potential of imidazole, oxazole and thiazole hybrids, and the structure–activity relationships (SARs) are also discussed to facilitate further rational design of more effective candidates, covering articles published from 2012 to 2022.     

Synthesis and NMR spectral assignments of novel nitrogen and sulfur heterocyclic compounds

Synthesis and NMR spectral studies of multidentate N and S heterocycles, 1,3,5-tris(N-methylbenzimidazolyl)benzene, 1,3,5-tris(benzimidazolyl)benzene,1,3,5-tris(benzothiazolyl) benzene, 2,2'-bipyridine 3,3'-bis(benzothiazolyl)benzene and 1,2,4,5-tetrakis(benzothiazolyl) benzene have been carried out. 2D (1)H-(1)H PFG-COSY as well as (1)H-(13)C single and multiple bond correlated (2D GRASP-HSQC and GRASP-HMBC) experiments have been employed to characterize the compounds. 1D NOE experiments have been useful in understanding the structure of 1,3,5-tris(N-methylenzimidazolyl)benzene.