Study Of Tautomerism Research Articles

Theorectical Study of Tautomerism, Physicochemical and ADMET Properties of 2-Pyridone Derivatives

Theorectical Study of Tautomerism, Physicochemical and ADMET Properties of 2-Pyridone Derivatives

15N NMR study of azo-hydrazo tautomerism in some industrially produced azo dyes

15N NMR data (1J (15N, 1H) coupling constants and 15N chemical shifts) were used to characterize quantitatively azo-hydrazo tautomerism in some industrially produced azo dyes. Both 1J (15N, 1H) coupling constants and 15N chemical shifts were obtained at the natural abundance level of 15N using inverse detection of resonances. All three possible types of azo dye existence were found: (i) dyes existing completely in azo forms, (ii) dyes existing completely in hydrazo forms or (iii) dyes forming azo-hydrazo tautomeric equilibria.

Experimental and theoretical study of the cytosine tautomerism through excited states.

The irradiation of water solution of cytosine with UV light (λmax = 254nm) shows oxo-hydroxy tautomerism with a rate constant of 6.297 × 10-3min-1. The order of the reaction implies a tautomeric conversion. After removing the UV light source, we observed a dark reaction with a rate constant of 1.473 × 10-3min-1 which leads to a restoration of the initial tautomer as before the irradiation. The mechanism of oxo-hydroxy tautomerism of cytosine in water solution was studied in the excited state. It was found that the transformations occur along the 1πσ* excited-state reaction paths which link the Franck-Condon geometries of the tautomers and the conical intersections S0/S1 connected with the H-detachment processes of the corresponding bonds. Furthermore, we established that the conical intersections S0/S1 are also mutually accessible along the 1πσ* excited-state reaction paths. The ground-state equilibrium geometries were optimized at the B3LYP/aug-cc-pVDZ level of theory in water environment according to PCM as well as at the CC2/aug-cc-pVDZ level in the gas phase. The TD B3LYP and CC2 methods were applied for the study of the excited states. The tautomerization mechanisms were studied with the use of the linear interpolation in internal coordinates approach using the optimized geometries of tautomers minima and conical intersections S0/S1 at the CASSCF(6,6)/6-31G* level. All calculations were performed with the GAUSSIAN 16 commercial software.

Single-crystal X-ray diffraction studies of pressure-induced valence tautomerism in a cobalt–dioxolene complex

Single-crystal X-ray diffraction studies of pressure-induced valence tautomerism in a cobalt–dioxolene complex

Structural study of some unsaturated malononitriles using mass spectrometry and theoretical models

AbstractThe study of tautomerism has gained relevance in the scientific community because several cellular processes occur through different tautomeric forms of certain compounds. The percentage of each tautomer in compounds with tautomerism capability depends on numerous factors, such as temperature and solvent polarity, among others; and, by changing the external conditions, equilibrium displacement can be established very quickly. This manuscript deals with nitrile–ketenimine tautomerism in some unsaturated malononitriles. This kind of compounds with two nitrile groups conjugated to a double bound is able to rearrange accessible hydrogens and provide new and complex structures of different functionalities. The authors' motivation for investigating these compounds lies in understanding their tautomeric behavior in solution and gas phases and to predict reaction deportment to then account for the final products obtained. Four unsaturated malononitriles were synthesized to study the substituent effect on equilibrium displacement. Characterization was performed using nuclear magnetic resonance (NMR) and tautomeric equilibrium in gas phase was evaluated by mass spectrometry. Correlation with theoretical calculations was carried out in order to comprehend the system behavior.

15N NMR study of azo-hydrazo tautomerism: Past and present

15N NMR data (1J(15N, 1H) coupling constants and 15N chemical shifts) seem to be the most suitable ones to characterize azo-hydrazo tautomerism quantitatively. The reason is that nitrogen atoms of –NN−/−NH-N = fragments are directly involved in azo-hydrazo equilibrium.First data was measured and published in 1970 and 15N selectively enriched compounds had to be prepared since electro magnets were used in NMR spectrometers at that time providing very low resonance frequencies (from 60 to 100 MHz for protons) and have had, consequently, very low sensitivity. Moreover, a choice of 15N enriched 15N anilines was very limited and these compounds were relatively very expensive.At present, the situation is completely different. There has been a huge increase of NMR spectrometer frequencies used for measurement of NMR spectra and even routinely used NMR spectrometers having 400–600 MHz proton frequencies are sufficiently sensitive to provide 1J(15N, 1H) coupling constants and 15N chemical shifts at the natural abundance level of15N. Inverse detection of resonances is now routinely used. The lower magnetogyric ratio of appropriate nucleus the higher signal enhancement is achieved: this is the very case of the 15N isotope. Theoretical enhancement factor obtained for inverse detection of 15N compared with direct one is ca 300! Application of cryoprobes where electronics is chilled either by liquid nitrogen or even liquid helium reducing electric noise allows to reduce time of accumulation from 8 to 16 times!Some representative examples are presented both from past to present demonstrating the fact that thorough analyses of NMR spectra allow determining the proper constitutions of compounds studies and excluding the wrong ones.

Experimental and theoretical studies on prototropic tautomerism of 1-tetralone-2-carbothioamides and synthesis of regioselectively designed fused 2H-indazole derivatives

Condensation of 1-tetralones with phenylisothiocyanate in presence of sodium hydride produced 1-oxo-N-phenyl-1,2,3,4-tetrahydronaphthalene-2-carbothioamides 2a–b. The structure of carbothioamides 2 was established on the basis of spectral data. Prototropic tautomerism studies of carbothioamide 2a were investigated in solution by NMR (1H and 13C NMR), electronic spectroscopy and gas chromatography techniques. The proton transfer behaviour in solid state and gaseous phase was studied utilizing FT-IR and Mass spectral studies, respectively. DFT approach was used to accomplish the theoretical computations. The ground state geometries of different tautomers were optimized using B3LYP method and 6-31G(d) basis set. The vibrational and NMR spectra of different tautomers were calculated and correlated with the experimental results. HOMO-LUMO studies of different probable tautomers of carbothioamide 2a were employed in determination of chemical reactivity descriptors.The dynamic photoisomerization experiments were performed in chloroform under UV irradiation (UV lamp, 15W) and spectra were recorded to investigate the photo dynamic keto ⇌ enol ⇌ thioenol tautomerization. Further, condensation of carbothioamides 2 with hydrazine and its aryl derivatives regioselectively furnished 4,5-dihydro-2H-benzo[g]indazole derivatives 3. Spectrochemical characterizations and single crystal X-ray diffraction analysis of representative indazole derivative 3b resolved the structural ambiguity between the possible 2H-indazole 3 and 1H-indazole 4 regioisomers. Also, the optimized geometric bond lengths and bond angles, obtained by using DFT studies, were compared with the values obtained from X-ray diffraction. The regioselectivity of 3 was justified by root mean square deviations (RMSD) calculations which shows the minimum deviation for 2H-indazole derivative 3.

Theoretical study of keto-enol tautomerism in 7-epi-clusianone by quantum chemical calculations of NMR chemical shifts.

Plants from the Garcinia genus have been used worldwide due to their therapeutic properties. Among the various metabolites isolated from this genus, 7-epi-clusianone, a tetraprenylated benzophenone, stands out for its wide range of identified biological activities. This benzophenone can exist in five tautomeric forms, although the benzene-d6 and chloroform-d3 solution nuclear magnetic resonance (NMR) spectra revealed only two tautomeric forms (B and C) in equilibrium, with concentration ratio depending on the solvent in which the spectrum was obtained. Calculated energy values suggested that tautomeric forms B and E would be prevalent in benzene-d6 solution, in contrast to the experimental data. Considering this conflicting result, we employed the statistical DP4 + method based on 13C and 1H NMR chemical shift calculations, in the gas phase and in benzene-d6 solution, to confirm that the B and C tautomeric forms of 7-epi-clusianone are the most prevalent in the experimental conditions.

Synthesis and study of azide-tetrazole tautomerism in 2-azido-6-phenylpyrimidin-4(3H)-one and 2-azido-4-chloro-6-phenylpyrimidine

Synthesis and study of azide-tetrazole tautomerism in 2-azido-6-phenylpyrimidin-4(3H)-one and 2-azido-4-chloro-6-phenylpyrimidine

A theoretical study of the valence tautomerism of 1H-pyrazolium-4-olates (X = O) and related compounds (X = S, Se, NH): relative stabilities, protonation effects, and tautomerization barriers

The valence isomerism of a series of heterocyclic mesomeric betaines (HMBs) belonging to class 5, called pseudo-semi-conjugated HMBs, has been studied theoretically both the neutral and the protonated species. These HMBs are 1H-pyrazol-2-ium-4-olates and related compounds where the oxygen atom has been replaced by S, Se atoms, and an NH group. The main conclusion of the present work is that the ring/open valence tautomerism is possible both for neutral and protonated although it has never been observed experimentally.

Synthesis, prototropic tautomerism studies of indenocarbothioamides and their conversion to biologically active indenothiazole derivatives

Indenocarbothioamides 2, obtained from reaction of indane-1,3-dione with aryl isothiocyanates, on condensation with 3-chloropentane-2,4-dione and chloroacetyl chloride furnished 1,3-indanedione coupled thiazole and thiazolidin-5-one derivatives, respectively. The structure of the obtained products was assigned on the basis of spectral data (IR, NMR and Mass). Prototropic tautomerism studies of carbothioamides 2 were carried out in solution (1H NMR, 13C NMR and UV–vis), gas phase (Mass) and solid state (IR and X-ray). X-ray diffraction studies of carbothioamide 2a have revealed the existence of enolic form in the solid state. DFT studies of various possible tautomeric forms in gas phase as well as in solution state corroborated by the experimental results. Antibacterial studies of indenothiazole and indenothiazolidin-5-one derivatives have been reported.

Synthesis, Tautomerism Study, Antimicrobial Evaluation and Cytotoxicity of Some New Bis(Arylazo)-Terpyrazoles

The chemistry of α-(arylhydrazono)-β-ketoaldehydes has recently received considerable attention and they are frequently employed as synthons in organic synthesis and their structural features are part of biologically active compounds. Thus, the present studies research describe the novel series synthesis of 3,3'-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis(2-arylhydrazono-3-oxo-propanal) 3a-i via coupling reactions of sodium 3,3'-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis(3-ox

Synthesis and computationally assisted spectroscopic study of tautomerism in 3-(phenyl(2-arylhydrazineylidene)methyl)quinoxalin-2(1H)-ones

Implicit and explicit quantum mechanical modeling of solutions of a series of quinoxalinone-based hydrazones allowed to describe their tautomeric/isomeric/conformational composition and IR and UV-Vis spectra.

Spectroscopic, X-ray and DFT studies of prototropic tautomerism and photophysical properties of regioselectively designed new 3-, 2,3-substituted tetrahydro[4H]indazol-4-ones

• Regioselective synthesis of new 3-, 2,3-substituted tetrahydro[4 H ]indazol-4-one derivatives • Prototropic tautomerism studies by spectral, LC-MS and DFT studies • Computational studies on tautomers and regioisomers for structure validation • X-ray diffraction studies of representative compound • Photophysical studies of new obtained products have been reported Reaction of dimedone and arylisothiocyanate in triethyl amine produced carbothioamide 2 which on condensation with hydrazine or phenyl hydrazine generated 3-substitued-2 H -indazole 3 or 2,3-disubstituted-2 H -indazole 5, respectively instead of the expected regioisomers 3-substitued-1 H -indazole 4 or 1,3-disubstituted-1 H -indazoles 6. Spectral data (IR, NMR and Mass) were of little help for structural differentiation. The prototropic tautomerism studies of 3-substituted-2 H -indazol-4-ones have been described on the basis of spectral, LC-MS and DFT studies. The structural ambiguity was resolved by X-ray diffraction studies of compound 5 and validated by theoretical studies on the structure 5a and its regioisomer 6a . Photophysical studies (UV and fluorescence) of compounds 3 and 5 in different solvents are also reported.

The Reactivity of Azidonitrobenzofuroxans towards 1,3-Dicarbonyl Compounds: Unexpected Formation of Amino Derivative via the Regitz Diazo Transfer and Tautomerism Study.

Herein, we report on the reaction of nitro-substituted azidobenzofuroxans with 1,3-dicarbonyl compounds in basic media. The known reactions of benzofuroxans and azidofuroxans with 1,3-dicarbonyl compounds in the presence of bases are the 1,3-dipolar cycloaddition and the Beirut reaction. In contrast with this, azidonitrobenzofuroxan reacts with 1,3-carbonyl compounds through Regitz diazo transfer, which is the first example of this type of reaction for furoxan derivatives. This difference is seemingly due to the strong electron-withdrawing effect of the superelectrophilic azidonitrobenzofuroxan, which serves as the azido transfer agent rather than 1,3-dipole in this case.

15N, 13C and 1H NMR study of tautomerism in 2-(phenyldiazenyl-4-substituted naphthalen-1-ols. Influence of substitution in passive components on azo-hydrazo tautomerism

The one- and two-dimensional 15N, 13C and 1H NMR spectra of benzenediazonium chloride coupling product with 4-R-naphthalene-1-ols (R = NO2(1), Br (2), Cl (3), H (4), OCH3(5)) were measured and analysed. It was found that the reaction products exist predominantly in hydrazone forms. Contrary to previously published influence of substituents in diazonium salts, where more electron acceptor types of substituents cause increase contents of hydrazo forms, the situation in compounds 1–5 is completely opposite. Moreover, hydrazone content in 4-nitro-2-[(E)-(4-nitro-phenyl)diazenyl]naphtalen-1-ol (6) combining substitution both in position 4 of passive component and position 4 of active component (i. e. diazonium salt) is higher compared with that in 4-nitro-2-[(E)-(phenyl)diazenyl]naphtalen-1-ol (1).

Comparative studies of excited state intramolecular proton transfer (ESIPT) and azo-hydrazone tautomerism in naphthalene-based fluorescent acid azo dyes by computational study

Abstract We found that benzothiazole is responsible for enhancing fastness properties of dyes. On comparing the total electronic energies of naphthol tautomers (−1425.16 eV) and its analogs (−2146.59 eV), we found that benzothiazolyl series is more stable than the naphthol series. Frontier Molecular Orbitals (FMOs) also show flow of charge transfer from the donor to the acceptor in benzothiazole-containing compounds, whereas it is absent in plane naphthol series. Among the benzothiazolyl isomers, the hydrazone form is found to be more stable and responsible for fluorescence possession. Highest Occupied Molecular Orbital (HOMO)–Lowest Occupied Molecular Orbital (LUMO) energy band gap also indicates the same. Electrophilicity index and hyper-hardness values of both the series were found to be positive which directly ratifies photostability and reactivity. Benzothiazolyl series was found to be more stable, hence light fastness, enhanced.

DFT and TD-DFT Study of Favipiravir Tautomerism as RNA Polymerase Inhibitors : COVID-19

Favipiravir is an antiviral medication currently being trialled as a COVID-19 treatment. To help accelerate these efforts, we have performed a research for tautomers formations of favipiravir as possible RNA polymerase enzyme inhibitors and mitigating the virus ability. This study provides important electronic and optical properties of tautomers determined by density functional theory (DFT) and time-dependent density function theory (TD-DFT) calculations in gas phase and in water. A series of favipiravir derivatives was designed, and study the effect of the HOMO-LUMO energy gap on the efficacy of inhibitors. It has been determined that H-atom positions change and substituting fluorine (F) by hydroxyl (OH) group of tautomers affects the energy gap and dipole moment values. Among all compounds, the results have shown that Fb4 form with OH is most potent inhibitory activity in both gas phase and water. These investigations indicated that these tautomers could be potentially developed into drugs, but further investigations are still required to examine the cytotoxicity and consequent side reactions.

Spectral study of thione-thiol tautomerization of thiourea in aqueous alcohol solution

In this work we studied the equilibrium of thione–thiol tautomerization by Raman and UV spectroscopies. This type of tautomerization influences on the course and direction of the reaction between thiourea and other organic compounds. The studies were carried out in water and aqueous alcohol medium. Мethanol, ethanol, propanol-1 and propanol-2 were used as alcohols. Hydrochloric acid was used to protonate thiourea in water and aqueous alcoholic solutions. UV spectroscopy made it possible to establish the tautomer ratio in water and aqueous alcohol solutions as the ratio of the intensities of absorption bands at 236 and 200 nm. There is an increase in the content of the thiol form and a decrease of the thione form observed in the row water-methanol-ethanol-propanol-isopropyl alcohol. The addition of hydrochloric acid to the thiourea water or aqueous alcohol solutions leads to the increase of the thione form and to the decrease of the thiol form in the composition. The thione form of thiourea can be determine by Raman spectra of –C=S group. The thiol form of thiourea is difficult to detect by Raman spectroscopy due to the overlap of the –S–H bond absorption band with alcohols absorption bands.

Tautomeric Study of Schiff Bases Derived from o‐Dihydroxybenzaldehyde by UV‐Vis, IR, 1H NMR, 13C NMR Spectroscopy and Computational Modeling.

AbstractTautomeric equilibria at room temperature were studied for three aromatic imine polyol compounds, previously reported 2‐((2‐hydroxybenzylidene)amino)‐2‐(hydroxymethyl)propane‐1,3‐diol 1 and two new compounds 2‐(((1,3‐dihydroxy‐2‐(hydroxymethyl)propan‐2‐yl)imino)methyl)benzene‐1,4‐diol 2 and 3‐(((1,3‐dihydroxy‐2‐(hydroxymethyl)propan‐2 yl)imino)methyl)benzene‐1,2‐diol 3. The dynamic behavior of these equilibria is described by a combination of IR, UV‐Vis and NMR spectroscopic measurements with DFT and TDDFT calculations in condensed phase. Among the different approaches, the combination of UV‐Vis experimental spectra with the oscillator strengths values estimated from TDDFT calculations allowed for the assessment of the tautomeric populations in DMSO and methanol. These results were consistent with different functionals employed GGA, Hybrid and MetaGGA.