Enolization Process Research Articles

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas.

Solutions of 1,3-diketones and 1,3-ketoester derivatives react with fluorine to give the corresponding 2,2-difluoro-1,3-dicarbonyl derivatives in the presence of quinuclidine. Quinuclidine reacts with fluorine in situ to generate a fluoride ion that facilitates limiting enolization processes, and an electrophilic N-F fluorinating agent that is reactive towards neutral enol species.

Chiral Lewis Acid-Catalyzed Norrish Type II Cyclization to Synthesize α-Oxazolidinones via Enantioselective Protonation

Chiral Lewis Acid-Catalyzed Norrish Type II Cyclization to Synthesize α-Oxazolidinones via Enantioselective Protonation

Photoenolization/nucleophilic addition enables direct access to 3-alkyl-3-hydroxy-indolin-2-ones

A light-driven, catalyst- and additive-free photoenolization/nucleophilic addition reaction for the synthesis of 3-benzyl-3-hydroxyindolin-2-ones is presented. In this reaction, 2-methylbenzophenones undergo light-induced enolization process to afford hydroxy-o-quinodimethanes (hydroxy-o-QDMs), which are then immediately captured by the electrophilic isatins. The reaction utilizes green and clean light energy to realize the C–H activation of the inert benzyl position of 2-methylbenzophenones. This method tolerates a wide scope of substrates and provides concise access to a series of novel 3-benzyl-3-hydroxyindolin-2-ones with 60–99% yields.

Ni-Catalyzed asymmetric reduction of α-keto-β-lactams via DKR enabled by proton shuttling.

Chiral α-hydroxy-β-lactams are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective dynamic kinetic resolution (DKR) of α-keto-β-lactams was realized via a novel proton shuttling strategy. A wide range of α-keto-β-lactams were reduced efficiently and enantioselectively by Ni-catalyzed asymmetric hydrogenation, providing the corresponding α-hydroxy-β-lactam derivatives with high yields and enantioselectivities (up to 92% yield, up to 94% ee). Deuterium-labelling experiments indicate that phenylphosphinic acid plays a pivotal role in the DKR of α-keto-β-lactams by promoting the enolization process. The synthetic potential of this protocol was demonstrated by its application in the synthesis of a key intermediate of Taxol and (+)-epi-Cytoxazone.

Palladium-Catalyzed Controllable Reductive/Oxidative Heck Coupling between Cyclic Enones and Thiophenes via C-H Activation.

Herein, we report a straightforward, environmentally friendly, and controllable palladium/ligand catalytic system to enable reductive/oxidative Heck reactions of cyclic enones with thiophene or furan derivatives via C-H activation. The key to this tunable reaction is the appropriate intercepting thienyl-Pd(II)-enolate during the enolization process. Such a controllable and economic protocol would not only provide efficient methods to construct various value-added β-heteroarylated cyclic ketones/enones but also shed light on developing other conjugate addition reactions via C-H activation.

Effect of beryllium bonds on the keto–enol tautomerism of formamide derivatives: a subtle basicity–acidity balance

The effects of the association of BeH2 to formamide derivatives have been investigated through the use of G4 high-level ab initio calculations. The association takes place preferentially at the carbonyl group of the amide in the keto tautomer and to the imino group in the enol form. In both cases, the complexes formed are stabilized through the formation of beryllium and dihydrogen bonds. The relative stability of these complexes is the result of a subtle balance between the changes induced by the formation of the beryllium bond on the intrinsic basicity and acidity of the amide. One of the main consequences of this balance is the significant stabilization of the enol tautomer due to the concomitant increase in the basicity of the imino group with respect to the carbonyl group and the significant acidity enhancement of the OH group, which leads to the formation of very strong BeH···HO dihydrogen bonds in the enol complexes. For the Cl-, Br- and NO2-formamide derivatives, this dihydrogen bond is so strong that a spontaneous formation of hydrogen molecule takes place. The formation of the beryllium bond not only stabilizes the enol forms, but also leads to a significant decrease in the activation barriers involved in the enolization process.

Mechanistic insights on the iodine(III)-mediated α-oxidation of ketones.

The synthesis of α-substituted carbonyl compounds is of great importance due to their ubiquity in both natural and man-made biologically active compounds. The field of hypervalent iodine chemistry has been a great contributor to access these molecules. For example, the α-oxidation of carbonyl compounds has been one of the most investigated iodine(III)-mediated stereoselective transformations. Yet, it is also the transformation that has met the most challenge in terms of achieving high stereoselectivities. The different mechanistic pathways of the iodine(III)-mediated α-tosyloxylation of ketones have been investigated. The calculations suggest an unprecedented iodine(III)-promoted enolization process. Indications that iodonium intermediates could serve as proficient Lewis acids are reported. This concept could have broad impact and foster new developments in the field of hypervalent iodine chemistry.

Why Is the Spontaneous Deprotonation of [Cu(uracil)2](2+) Complexes Accompanied by Enolization of the System?

The reaction-force formalism is applied to carry out a detailed analysis of the mechanisms behind the enolization processes undergone by the complexes formed on interaction of uracil dimers with Cu(2+) ions after spontaneous deprotonation of the resulting complexes. These enolization processes apparently involve a single proton transfer (PT) from an NH group to a carbonyl group of the same uracil moiety, which should involve a rather high activation barrier that prevents the process occurring. However, the reaction-force, chemical-potential, and electronic-flux profiles unambiguously indicate that the actual mechanism involves three low-barrier elementary steps, and this explains why enolization of the [Cu(uracil-H)(uracil)](+) complexes is a highly facile, assisted PT process. All of the observed PT processes show a typical profile for both the chemical potential and the electronic flux associated with the bond-breaking and the bond-formation processes.

Photoenolization via excited state double proton transfer induces "turn on" fluorescence in diformyl diaryl dipyrromethane.

A light triggered enolization in diformyl diaryl dipyrromethane by excited state dual proton transfer (ESDPT) induces "turn on" fluorescence. The role of diaryl and diformyl groups in the enolization process was confirmed by photophysical and theoretical studies.

Photothermal Tautomerization of a UV Sunscreen (4-tert-Butyl-4′-methoxydibenzoylmethane) in Acetonitrile Studied by Steady-State and Laser Flash Photolysis

The photothermal tautomerization processes between enol and keto forms of 4-tert-butyl-4'-methoxydibenzoylmethane (trade name, Avobenzone) in acetonitrile have been studied by steady-state and laser flash photolysis. The keto form is produced upon photolysis of the enol in only acetonitrile with a quantum yield of 0.014. The molar absorptivity of the keto form was determined. Phototautomerization from the keto to the enol form was not seen. Laser flash photolysis of the keto form recognized the formation of the triplet state. In the dark, the keto form underwent thermal tautomerization to the enol with a lifetime of 5.1 h at 295 K. The enolization rate in acetonitrile was not accelerated by the presence of alcohols and/or water but increased with increasing temperature and followed the Arrhenius expression. The activation energy and the frequency factor were determined for the enolization process from the keto to the enol form. On the basis of the energy states of the tautomers and isomers as estimated by DFT calculations, a schematic energy diagram was determined for the photothermal tautomerization processes in acetonitrile.

Functionalized Graphene for High Performance Lithium Ion Capacitors

Lithium ion capacitors (LICs) have recently drawn considerable attention because they utilize the advantages of supercapacitors (high power) and lithium ion batteries (high energy). However, the energy densities of conventional LICs, which consist of a pair of graphite and activated carbon electrodes, are limited by the small capacities of the activated carbon cathodes. To overcome this limitation, we have engaged urea-reduced graphene oxide. The amide functional groups generated during the urea reduction facilitate the enolization processes for reversible Li binding, which improves the specific capacity by 37 % compared to those of conventional systems such as activated carbon and hydrazine-reduced graphene oxide. Utilizing the increased Li binding capability, when evaluated based on the mass of the active materials on both sides, the LICs based on urea-reduced graphene oxide deliver a specific energy density of approximately 106 Wh kg(total) (-1) and a specific power density of approximately 4200 W kg(total) (-1) with perfect capacity retention up to 1000 cycles. These values are far superior to those of previously reported LICs and supercapacitors, which suggests that appropriately treated graphene can be a promising electrode material for LICs.

Theoretical studies on the isomers and tautomers of 22-membered macrocyclic ligand

Density functional theory (DFT) calculations at B3LYP/6-31+G(d) in the gas phase and ethanol have been used to study different isomers and tautomers of a novel macrocyclic ligand ( L) synthesized recently from diethyloxalate and dipropylenetriamine. The relative stability of 21 isomers and tautomers shows that this compound exists mainly, in the gas phase and ethanol solution, as a tetra-keto tautomer. The most stable form has all C O and NH moieties in anti configurations with each other. Flipping of one NH group to the syn position destabilizes the resulting isomer by 11 kcal/mol with an energy barrier of 38 kcal/mol. Enolization processes are hindered by higher energy barriers of 42 and 45 kcal/mol in the gas phase and ethanol, respectively. Charges on different atoms and NBO analysis, were used to explain the electronic structures of these systems. The calculated structures and frequencies of the ligand agree with the previously reported experimental data.

ChemInform Abstract: Diastereoselective Aldol Condensation of Directly Generated Titanium Enolates of Activated Esters.

Abstract Simply generated (TiCl 4 , Et 3 N, −78°C) titanium enolates of some thioesters and α-thio substituted esters undergo aldol condensations with achiral and chiral aldehydes with low to high stereoselectivity. An 1 H-NMR study of the TiCl 4 /ester complexation and of the enolization process is presented. The relation between the enolate structure and the aldol product stereochemistry is discussed.

Photoacoustic measurement of ethylene as a real time biomarker of lipid peroxidation processes in mice

In some diseases the accumulated endogenous δ-aminolevulinic acid (δ-ALA), with a pH between 7 and 8, undergoes an enolization process that produces free radicals. It is expected that most of the exogenously-supplied δ-ALA in healthy organisms will be converted into protoporphyrin IX (PpIX), and ultimately to the hem group, but a small accumulation of δ-ALA, when present, will initiate a lipid peroxidation process due to the generation of oxygen-reactive species. Some of the end products commonly found in lipid peroxidation include ethane, pentane, and ethylene as well as other hydrocarbons. As these gases are normally produced at trace levels, sensitive techniques are needed for their measurement. In this work, the peroxidative effect of exogenously-supplied δ-ALA and CCl4 in female CD1 mice has been studied by photoacoustic trace gas detection. Exhaled ethylene from δ -ALA-administered mice reached concentrations of few ppbV for approximately 30 minutes, after application of δ-ALA.

Additive effects of methyl ketones in the Belousov-Zhabotinsky reactions

The role of the methyl ketones in oscillating reactions of the Belousov-Zhabotinsky (BZ) type is to eliminate bromine through an enolization process, but its importance in the dynamic of the reaction depends upon the organic compound that is used as substrate. This work shows that in a binary mixture of methyl ketones every ketone acts independently, but with an additive effect in the dynamics of the BZ reaction. The results obtained are supported by numerical simulations based upon the mechanisms for both reactions.

Ab Initio Study on the Effects of the Substituent and the Functional Group on the Isomerization of H3CC(X)Y and H2C(X)CHY (Y = SiH2, PH, S; X = H, CH3, NH2, OH, F)

We report the effects of the substituent and functional group on the tautomerizations of H3CC(X)Y and H2C(X)CHY (Y = SiH2, PH, S; X = H, CH3, NH2, OH, F) at the G2 level of theory. In the Y = SiH2 series, the enol forms (H2CCXSiH3) are thermodynamically more stable than their counterparts, by ca. 20−30 kcal/mol, regardless of their site of substitution. In the Y = PH and S cases, the keto forms (H3CC(X)PH, H3CC(X)S) are thermodynamically more stable than their counterparts by ca. 2−12 kcal/mol for the 1-substituted series, while for the 2-substituted series the enolization processes are either endothermic or exothermic, with their relative energies near 0. Combining these results with those from the previous study, the enolization is endothermic when the non-hydrogen atom in Y is more electronegative than a carbon atom and is exothermic if the former is more electropositive than the latter. Substituents with π-donating ability in the 1-substituted series increase the relative energy when Y = PH and S, but they decrease it when Y = SiH2. On the other hand, in the 2-substituted series, the relative energies decrease in the sequence H > CH3 > F > OH > NH2, which is the opposite order of the increasing π-donating abilities of these substituents. The barriers to enolization in this study range from 36 to 61 kcal/mol at the G2 level of theory. The effects of the functional groups and substituents on the energy barriers are explained by interpreting Hammond's postulate in terms of the position of the transition structure along the reaction coordinate, nT, defined by Agmon, Pearson's principle of hard and soft acids and bases, and Hammett's electron push/pull effect. By Mulliken population analysis, the electronic charge of the migrating hydrogen atom becomes gradually negative, which indicates the tautomeric interconversion is as an Hδ- transfer (or a hydride transfer). This is in contrast with that of the analogous process that occurs for compounds of the second period (Y = O, NH, and CH2).

Transition State Structures and Intermediates Modeling Carboxylation Reactions Catalyzed by Rubisco. A Quantum Chemical Study of the Role of Magnesium and Its Coordination Sphere

The reactive sequences mimicking the carboxylation chemistry catalyzed by Rubisco are characterized at HF/3-21G and HF/6-31G** calculation levels. Hydroxypropanone, C1H3−C2O−C3H2OH, represents the substrate D-ribulose-1,5-bisphosphate, while the enzyme active site is modeled with residues found at the coordination sphere of magnesium: a carbamylated ammonia (Lys 201), two formiate (Asp 202 and Glu 204), and one water molecule. Theoretical characterization of saddle points of index one, transition state (T-S) structures, starts with an intramolecular enolization process previously reported, yielding an enediol intermediate (carbonyl oxygen at C2 is transformed into alcohol, C2-OH). The CO2 addition, with a concomitant hydrogen transfer from the C3-OH to carbon dioxide constitutes the second step, with formation of a carboxy-ketone (carboxy-aldehyde in our model) intermediate, C1H3−C2OH(COOH)−C3HO. Adding a water molecule at C3 is the third step, followed by the C2−C3 bond break. This process is coupled with another intramolecular hydrogen transfer, yielding in the real substrate 3-phospho-D-glycerate and an intermediate. A final step involving this intermediate is associated with the C2 inversion with formation of another molecule of 3-phospho-D-glycerate. A detailed comparison of T-Ss with and without inclusion of the residues forming the magnesium coordination sphere is presented. Except for the already reported enolization T-S and also for one of the C2−C3 bond rupture T-Ss, the key geometric elements and the amplitudes of the transition vectors are fairly invariant to the presence of the magnesium coordination sphere. The reported transition structures are joined in order by appropriate precursor and successor complexes reflecting the real chemistry. The present model can hence be related to a sequential ordered kinetics. Most experimental aspects of the reaction pathways catalyzed by this key enzyme find explanation within the molecular mechanism obtained from the present theoretical results.

Chlorodicyclohexylborane-mediated aldol additions of alpha,alpha'-dioxygenated ketones.

Boron aldol additions of variously O-protected alpha,alpha'-dioxygenated ketones using dicyclohexylboron chloride and a tertiary amine have been investigated. The stereoselectivity of the process was dependent on the protecting group on the alpha-oxygen atoms. Notably, ketones with bulky silyloxy groups gave syn aldols, most likely via Z enolates. This rules out the participation of chelates during the enolization process, at least in the presence of such sterically crowded protecting groups. An alternative explanation is offered.

Monitoring Carbonyl−Amine Reaction and Enolization of 1-Hydroxy-2-propanone (Acetol) by FTIR Spectroscopy

Infrared absorption bands characteristic of the aldehydo, keto, and enediol forms of 1-hydroxy-2-propanone (acetol) were identified and used to study the effect of solvent on the absorption frequencies and the effect of temperature and acid/base catalysis on the enolization reactions. The data indicated that, in addition to water, acids and bases can catalyze the enolization of 1-hydroxy-2-propanone and that the temperature inversely effects the rate of enolization under basic conditions. However, under acidic conditions, increasing the temperature favors the enolization process. In addition, the reaction of 1-hydroxy-2-propanone with a primary and a secondary amine was also monitored by Fourier transform infrared spectroscopy. The data indicated that at room temperature the rate of amine reaction was faster than the rate of its catalysis of enolization; however, below room temperature, the rate of base-catalyzed enolization became comparable with the rate of carbonyl-amine reaction forming both Heyns and Amadori adducts.

Ab initio study of the adsorption of acetone and keto-enol equilibrium on the MgO(100) surface

An ab-initio quantum mechanical study of the adsorption of acetone and 2-propenol on a clean MgO(100) surface is reported. Ab-initio Hartree-Fock calculations have been carried out using an embedded-cluster approach in which the environment is described by total ion potentials and point charges. Optimized geometries for both acetone and 2-propenol adsorbed on the surface have been obtained using two basis sets and several model clusters. The adsorbate-surface interaction is found to be weak and electrostatic in nature, although there is a relative stabilization of the enol tautomer. The effect of the surface on the keto-enol equilibrium is analyzed and explained on the basis of this differential adsorption. Surface reconstruction induced by the adsorbate is also considered. While the surface relaxation effects are found to be negligible for acetone, they appear to be larger for 2-propenol, and allowing the surface to relax changes the qualitative description of the enolization process since in this case an enolate species is found to be adsorbed on the surface.