Theoretical study on keto–enol tautomerism and isomerization in pyruvic acid

Isomerization and tautomerism of 12 isomers of pyruvic acid including 4 keto and 8 enol forms were studied at the MP2 and B3LYP levels of theory using 6‐311++G(2df,p) basis set, separately. Activation energy (E_a), imaginary frequency (υ), and Gibbs free energy (ΔG^#) of the considered isomerization and tautomerism reactions were calculated. Interconversion of the enol forms proceeds through two paths: (i) proton transfer and (ii) internal rotation. Activation energies for the proton transfer paths were in the range of 125–145 kJ/mol and for the internal rotation paths were in the range of 5–45 kJ/mol. Keto–enol tautomerism of pyruvic acid proceeds only through proton transfer route and their activation energies were in the range of 200–300 kJ/mol. Effect of microhydration on the transition state structures and activation energies was also investigated. It was found that the presence of a water molecule catalyzes the isomerization and tautomerism reactions of pyruvic acid so that the activation energies decrease. © 2013 Wiley Periodicals, Inc.     

High-yield and sustainable synthesis of quinoidal compounds assisted by keto–enol tautomerism

The classical synthesis of quinoids, which involves Takahashi coupling and subsequent oxidation, often gives only low to medium yields. Herein, we disclose the keto–enol-tautomerism-assisted spontaneous air oxidation of the coupling products to quinoids. This allows for the synthesis of various indandione-terminated quinoids in high isolated yields (85–95%). The origin of the high yield and the mechanism of the spontaneous air oxidation were ascertained by experiments and theoretical calculations. All the quinoidal compounds displayed unipolar n-type transport behavior, and single crystal field-effect transistors based on the micro-wires of a representative quinoid delivered an electron mobility of up to 0.53 cm² V⁻¹ s⁻¹, showing the potential of this type of quinoid as an organic semiconductor.

Facilitated by the highly efficient Pd-catalyzed coupling and keto–enol-tautomerism-assisted spontaneous air oxidation, various indandione-terminated quinoidal compounds have been synthesized in isolated yields up to 95%.     

Solvent-assisted catalysis mechanism on Keto–enol tautomerism of cyameluric acid

The keto–enol tautomerism of cyameluric acid, both in gas phase and in water and methanol solution, has been studied at the B3LYP/6-31++g(d,P) level of theory in this paper. The harmonic frequencies of all the structures are calculated. The results show that the transition states of the tautomerism are 4-membered ring conformations in gas phase, whereas 6-membered ring conformations in solution. In the first proton transfer, activation energy ΔE^# is 56.4 and 50.9 kJ/mol for water and methanol solution, respectively, which is much lower than that in gas phase (163.2 kJ/mol). Solvent molecules (water and methanol) produce an important catalytic effect in the tautomerism, especially for methanol-solvated system. NBO analysis shows that there is a strong interaction between cyameluric acid and solvent molecules in transition states. AIM charge analysis indicates that the keto–enol tautomerism shows a certain degree of proton transfer character. From the reaction enthalpy and reaction rate point of view, keto–enol tautomerism in water-solvated and methanol-solvated system is easier than that in gas phase. The keto–enol tautomerisms are endothermic both in gas phase and in solution, so the enol forms are less stable than the keto ones.     

An investigation of keto–enol tautomerism in N-vinyl-2-, and 3-pyrrolidinones using ab initio and density functional theory calculations

We investigated the protomeric tautomerism of N-vinyl-2-pyrrolidinone (NV2P) and N-vinyl-3-pyrrolidinone (NV3P) molecules, and considered the three neutral tautomers for NV2P (1a, 1b, 1c) and the five for NV3P (2a, 2b, 2c, 2d, 2e). Full geometry optimizations were carried out at the HF/6-31G**, HF/6-31+G** and B3LYP/6-31+G** levels in the gas phase and in water. Additionally, single-point MP2/6-31+G** calculations were performed on the HF/6-31+G** optimized geometries. The tautomerization processes in water (=78.54) were studied using the self-consistent reaction field theory. According to our estimations, the tautomerization of NV2P and NV3P molecules are not strongly influenced by the polar solvents, the improvement of the basis set quality and the electron correlation effects in the gas phase and in water. The calculated relative free energies (ΔG) predict that 1a and 2a are the energetically preferred tautomers in the gas phase and in water.     

Separation of keto–enol tautomers in β-ketoesters: a gas chromatography–mass spectrometric study

The gas chromatographic behaviour for some β-ketoesters was studied. Additionally, the feasibility of the gas chromatographic separation of the corresponding tautomer forms was examined. In this work mass spectrometric detection allowed identification of both keto and enol forms and an estimation of their relative amounts for methylacetoacetate, -chloromethylacetoacetate, ethylacetoacetate and -chloroethylacetoacetate. This finding demonstrates slow tautomerisation kinetics permitting the chemical identity maintenance of the tautomers.     

Distinguishing between keto–enol and acid–base forms of firefly oxyluciferin through calculation of excited‐state equilibrium constants

Although recent years have seen much progress in the elucidation of the mechanisms underlying the bioluminescence of fireflies, there is to date no consensus on the precise contributions to the light emission from the different possible forms of the chemiexcited oxyluciferin (OxyLH₂) cofactor. Here, this problem is investigated by the calculation of excited‐state equilibrium constants in aqueous solution for keto–enol and acid–base reactions connecting six neutral, monoanionic and dianionic forms of OxyLH₂. Particularly, rather than relying on the standard Förster equation and the associated assumption that entropic effects are negligible, these equilibrium constants are for the first time calculated in terms of excited‐state free energies of a Born–Haber cycle. Performing quantum chemical calculations with density functional theory methods and using a hybrid cluster‐continuum approach to describe solvent effects, a suitable protocol for the modeling is first defined from benchmark calculations on phenol. Applying this protocol to the various OxyLH₂ species and verifying that available experimental data (absorption shifts and ground‐state equilibrium constants) are accurately reproduced, it is then found that the phenolate‐keto‐OxyLH^– monoanion is intrinsically the preferred form of OxyLH₂ in the excited state, which suggests a potential key role for this species in the bioluminescence of fireflies. © 2014 Wiley Periodicals, Inc.     

N.m.r. studies on aromatic compounds. I—13C n.m.r. spectra of some mono- and disulpho-substituted hydroxycarboxylic acids

Carbon-13 n.m.r. spectra of 3-hydroxy-4-sulpho-2-naphthoic, 3-hydroxy-5-sulpho-2-naphthoic, 3-hydroxy-7-sulpho-2-naphthoic, 5-sulphosalicylic, 3-hydroxy-5,7-disulpho-2-naphthoic, 1-hydroxy-4,7-disulpho-2-naphthoic, and 3,5-disulphosalicylic acids were recorded with and without proton noise-decoupling. Analyses of the spectra were carried out for all compounds except 3-hydroxy-5-sulpho-2-naphthoic acid which dimerized. The fine splitting caused by long-range coupling was used in identifying the lines of the ¹³C n.m.r. spectra.     

N.m.r. studies in the heterocyclic series: XVII—carbon-13 spectra of indazole derivatives

The ¹³C chemical shifts of 17 indazole derivatives are discussed as a function of substituent effects and the N-1—H or N-2—H structure of indazole. The presence in solution of the N-1—H tautomer is confirmed.     

N.m.r. studies in the heterocyclic series: XVI—determination of the structure of 3-azidoindazole by 1H and 13C n.m.r. spectroscopy

The 1-NH structure for 3-azidoindazole has been demonstrated by the observation of ¹H? ¹H and ¹³C? ¹H couplings involving the hydrogen atom attached to nitrogen. A comparison between 3-azidoindazole and indazole shows that both compounds have the same tautomeric structure.     

N.m.r. characterisation of linkage isomers

Summary Halogenation of Ln^III, Ce^IV and ZrO^II -diketone/-ketoester derivatives and their mixed ligand complexes of the types Ln(AA)₂(Sal) and Ln(AA)(Sal)₂ by NCS, NBS and PyHBr₃ yield different isomeric products depending on the nature of the solvent medium, the reagent and the reaction time. The halogenation, if carried out in glacial acetic acid, irrespective of the reagent, yields the stable S-hall, product wherein the three chelate rings remain imperturbed in respect of metal coordination. When the reaction is carried out in 5% v/v DMF-CHCl₃ employingN-halosuccinimide and maintaining correct reaction times, it is possible to isolate individually three other isomeric products. The isomers prepared are Ln(OO)₃, Ln(OO)₂(OX), Ln(OO)(OX)₂ and Ln(OX)₃ where (OO) represents diketone oxygen linkage and (OX) represents diketone oxygen and substituted halogen linkage to the central metal ion. The four linkage isomers have been identified by a comparison of the number of observed³H n.m.r. or¹³C n.m.r. signals with those expected for a given isomer on the basis of symmetry considerations in the tris-chelated octahedral structures.     

Nitrogen-15 n.m.r. studies of 13C, 15N labeled arginine

¹⁵N n.m.r. spectra of [¹³C-2, 3-¹⁵N₂-guanidino]arginine and [¹³C, ¹⁵N₂] urea were obtained in D₂O and H₂O at a variety of pH values both with and without proton decoupling. The effects of the proton exchange rate are readily observable in the proton coupled ¹⁵N spectra. When the guanidino group is deprotonated (pK = 12.5), the terminal nitrogens give a single resonance 6.6 ppm downfield of the protonated species, indicating a rapid tautomeric exchange. The observed NH and CN couplings are compared with calculated values, and good agreement is found for ¹J(CN) using a Blizzard–Santry type calculation. The ramifications of the proton exchange on ¹⁵N n.m.r. spectra of amino acids and peptides are discussed.     

The keto→enol photoisomerization of N‐salicilydenemethylfurylamine: Nonadiabatic ab initio dynamics simulation

The photoinduced isomerization of cis‐keto and trans‐keto isomers in N‐salicilydenemethylfurylamine has been studied using the surface‐hopping approach at the CASSCF level of theory. After the cis‐keto or trans‐keto isomer is excited to S₁ state, the molecule initially moves to a excited‐state local minimum. The torsional motion around relative bonds in the chain drives the molecule to approach a keto‐form conical intersection and then nonadiabatic transition occurs. According to our full‐dimensional dynamics simulations, the trans‐keto and enol photoproducts are responsible for the photochromic effect of cis‐keto isomer excited to S₁ state, while no enol isomer was obtained in the photoisomerization of trans keto on excitation. The cis keto to enol and cis keto to trans keto isomerizations are reversible photochemical reactions. It is confirmed that this aromatic Schiff base is a potential molecular switch. Furthermore, the torsion of C N bond occurs in the radiationless decay of trans‐keto isomer, while it is completely suppressed by an intramolecular hydrogen bonding interaction in the dynamics of cis‐keto form. Moreover, the excited‐state lifetime of cis keto is longer than that of trans‐keto form due to the O···H N hydrogen bond.     

Nuclear magnetic resonance studies: VII—13C and 15N n.m.r. of diazo compounds

The ¹³C and ¹⁵N n.m.r. results for a series of diazo compounds are reported. It is found that the diazo carbon is shielded by an extraordinary amount compared with normal sp² hybridized carbons. The ¹⁵N chemical shifts reveal that the terminal nitrogen is deshielded relative to the central one. This is contrary to that expected from charge effects but support is found for this phenomenon in other systems. One-bond ¹³C? ¹⁴N coupling in diazomethane is also reported for the first time. INDO MO calculations of the charges and finite perturbation calculations of ¹³C? ¹⁴N and C? H couplings are compared with the experimental results.     

N.m.r. studies of a rate process in a bridged biphenyl: Resolution of a discrepancy between n.m.r. and polarimetric kinetic data

Total bandshape analysis of the temperature-dependent n.m.r. spectrum of the bridge methylene protons in 6,6-dicarbethoxy-1,2,3,4-dibenzcyclohepta-1,3-diene has been carried out to yield the following activation parameters: ΔG = 60.96 ± 0.17 kJmol^?1 (14.57 ± 0.04 kcal mol^?1), ΔH^? = 47.3 ± 0.8 kJ mol^?1 (11.3 ± 0.2 kcal mol^?1) and ΔS^? = ?45.6 ± 3.3 J mol^?1 K^?1 (?10.9 ± 0.8 cal mol^?1 K^?1). A value of ΔG^? in agreement with the above may be obtained from a bandshape analysis (at a suitable temperature) of the spectrum of the methylene protons in the carbethoxy groups. In our opinion, the rate process described by these activation parameters must be the configurational inversion of the biphenyl system, and thus the polarimetric data on this compound reported by Iffland and Siegel [J. Am. Chem. Soc. 80, 1947 (1958); half-life of 80 min at room temperature] are seriously called to question, as previously noted by Sutherland and Ramsay [Tetrahedron 21, 3401 (1965)]. We have attempted unsuccessfully to repeat the polarimetric work, and have been able to show by means of thin-layer chromatography in the cold, mass spectral analysis and polarimetry that an optically active impurity (as yet unidentified) is the most probable cause of the discrepancy.     

Polyaromatic ether–ketones and ether–keto–sulfones having various hydrophilic groups

Polyaromatic ether–ketones and polyaromatic ether–keto–sulfones were sulfonated by suspending the polymer powders in dichloroethane containing liquid sulfur tiroxide and trialkyl phosphate at room temperature. It was found that more than one sulfonic group can be introduced per each repeating unit of the polymers without degradation. The sulfonated polymers were soluble in various organic solvents, and solubility and mechanical properties depended on the initial molecular weight of polymers as well as the degrees of sulfonation. Strong films can be cast from their dimethylformamide solutions.     

Differences in the keto–enol equilibrium of [M + H]+ ions of bupropion formed by electron impact and fast atom bombardment ionization

The fragmentation of the protonated molecular ion of bupropion produced by collisionally induced decomposition is shown to depend on the ionization method used to form the [M + H]⁺ ion. The daughter ion products do not depend on the energy of decomposition, i.e. high- or low-energy collisions, but on the ratio of the keto-enol equilibrium as influenced by the ionization process.     

N.m.r. studies of complexes of molybdenum(VI) with tartaric acid in aqueous solution

Summary Complex formation between molybdate ions and R,R-(+)-tartaric acid has been studied in aqueous solution, and to a limited extent in DMSO, over a range of concentrations and pH at 298K, using¹H and¹³C n.m.r. techniques. Only four main species are evident; two, which have Mo: L ratios of 11 and 12, are bondedvia a carboxylic oxygen atom and an adjacent hydroxyl oxygen atom. The 12 species forms stereospecifically. The other two main species contain bridging tartaric acid molecules, and a 22 species, also formed stereo-specifically in solution, have been isolated and characterised in the solid state. A limited number of experiments with racemic acid and meso-tartaric acid indicate that only a few species are formed in these systems and with a good deal of stereospecificity also.     

Uracil–4-Hydroxyuracil tautomerism revisited

The tautomerism of the uracil-4-hydroxyuracil system is examined with the 3–21G basis set and full geometry optimization using gradient techniques. Single-point calculations at the 6-31G level were also done and the results compared with the 2-pyridone–2-hydroxypyridine system. The best ΔE(taut) obtained in this work is 74.1 kJ/mol.     

N.m.r. determination of wax esters in marine lipids

The proton n.m.r. spectra of lipids containing triglycerides and wax esters dissolved in CDCl₃ are characterized by seven sets of signals. The areas of the signals of terminal methyl group and of methylene protons of both wax ester and triglyceride were integrated. These were used to calculate the content of wax esters in lipids or oils. The rapid n.m.r. procedure is directly usable for natural lipids containing as low as 3 mg of wax esters in 50-mg samples with an error of about 7%. The method described compares favorably with t.l.c. determination.