Enolization and Related Reactions

The effects of cationic and zwitterionic micelles on the keto-enol tautomerism of 2-phenylacetyl-furan and -thiophene (73, X = O, S) have been studied in aqueous media.285 While the micelles perturb the equilibrium only slightly, the apparent acidity of one or other tautomer is increased, as the micelles have an affinity for the enolate. The systems also show lowered water rates at the minima of their pH-rate profiles, allowing an otherwise undetectable metal ion catalysis to be observed. 

Solvent and concentration effects on keto-enol tautomerization have been investigated in DMSO-water mixtures and aqueous micellar solutions, for 2-acetylcyclo-hexanone and 2-acetyl-1-tetralone.286 Dramatic rate increases aboves 60% DMSO content have been explained in terms of solvent structure solvent polarity alone cannot rationalize the effect. 

Using a transition state model for enolate formation and a database search, a thiourea with a pendant amine has been designed as a catalyst, and its ability to hydrogen bond the enolate of acetone explored.287 Both in-plane and out-of-plane hydrogen bonds, to a lone a pair and the carbonyl 7r-bond, respectively, were considered. 

Charge density analysis has been carried out for three reaction paths involving intramolecular hydrogen transfer the keto-enol tautomerism of acetaldehyde, the pinacol rearrangement of protonated ethane-1,2-diol, and the unimolecular decomposition of methanediol, reactions involving H-transfer between C O, C C, and O O atoms.288 

A computational study of intramolecular proton transfer in acetylacetone has been carried out.289 

Rate and equilibrium constant measurements for the enolization of 3-phenylcoumaran-2-one (82) in aqueous dioxane indicate an enol content of ca 0.1%, a pKg, of 8.9 (6.0 for the enol tautomer), and a fairly symmetrical transition state for enolate anion formation the Brpnsted Pb = 0.52 Below pH 5, enolization is independent of pH, occurring via O-protonation of the enolate. 

2-Bis [(trifluoromethyl)thio] acetaldehyde (83a) has been prepared from an enam-ine precursor (84), although refluxing in aqueous ethanolic HCl is required to effect this reaction.The aldehyde is less stable than its enol tautomer (83b), and many reactions typical of aldehydes fail. For example, addition of aqueous silver nitrate immediately yields the silver salt of (83b), rather than giving precipitation of (elemental) silver. The (trifluoromethyl)thio substituent has pseudohalogenic character and, together with the hydroxy group, stabilizes the alkene tautomer in the manner of a push-pull alkene. The enol-aldehyde equilibrium mixture in acetonitrile shows an apparent of 2.6 when titrated with aqueous hydroxide. 

Enolization and ketonization kinetics and equilibrium constants have been reported for phenylacetylpyridines (85a), and their enol tautomers (85b), together with estimates of the stability of a third type of tautomer, the zwitterion (85c). The latter provides a nitrogen protonation route for the keto-enol tautomerization. The two alternative acid-catalysed routes for enolization, i.e. O- versus Af-protonation, are assessed in terms of pK differences, and of equilibrium proton-activating factors which measure the C-H acidifying effects of the binding of a proton catalyst at oxygen or at nitrogen. 

Concerted acid-base catalysed enolizations of a range of simple aldehydes and ketones have been measured in water at 25 °C, using a range of substituted acetic acid-acetate buffers.The buffer plots yield rate constants for acid (A a) and base ( b) catalytic terms in the normal way at low buffer concentrations. Extension up to higher concentrations (as far as [total buffer] = 2 m, typically) yields the third-order term ( ab) via upward curvature of the plots. While ab does not have a simple correlation with either k or b, it does correlate with their product, i.e. 

Malonaldehyde, CH2(CHO)2, exists as an intramolecularly hydrogen-bonded enol (86) in the vapour phase. Molecular dynamics calculations suggest that while a short 

Isomer stabilities and activation energies have been calculated for keto-enol tautomerization of simple carbonyl compounds, MeC(R)=X (X = O R = H, Me) 129 both specific and bulk solvent effects have been analysed. Related isomerizations of acid derivatives (R = F, CN) and other related structures (R = H X = CF12, NH, S) are compared. 

Ah initio methods have been used to compare enzyme-catalysed enolization mechanisms.130 Acid- and base-catalysed stepwise mechanisms have been compared with the concerted reaction the latter is favoured by several hydrogen-bonding interactions. 

Simple enols stabilized by bulky aryl groups have been reviewed.131 Amide enols, tip2C=C(OH)NR1R2 (tip = 2,4,6-triisopropylphenyl), can be generated by reaction of amines with ditipyl ketene, are observable by NMR, and slowly tautomerize. Vinyl alcohols with two or three bulky aryls have propeller conformations and are chiral, but are not easily resolved. 

Acyclic perfluoroenols are strongly destabilized relative to their cyclic counterparts 132 the result is general for alkene systems.133 

Acetoacetic acid, MeCOCH CC H, can enolize via its ketone- or acid-carbonyl groups calculations suggest the former route is thermodynamically more favourable134 by 11.3kcalmol.  

Magnesium bis(hexamethyldisilazide), Mg(HMDS)2, catalyses the enolization of ketones.287 On addition to propiophenone in toluene at ambient temperature, a ca 3 1 E Z mixture of enolates (103, R=SiMe3) is formed. These enolates, and an initial ketone complex, have been characterized by NMR, X-ray, IR, and UV-visible spectroscopy and computational studies. Kinetics of tautomerization have been measured, with proton transfer confirmed as rate determining ( hAd = 18.9 at 295 K). The significant temperature dependence of the primary isotope effect is indicative of tunnelling. 

Enol (104), generated rapidly in acidic solution from a precursor acetal, shows remarkable stability fi/2 3 h in 0.1 mol dm-3 DC1 in CD3OD at 300 K, allowing its characterization by 2D NMR spectroscopy. A DFT study of a simple model, 2,2-difluoroethenol, indicates that there are significant differences in timing of the protonation TS compared with the non-fluorinated enol.288 

Keto-enol tautomerization of 3-hydropyridazine derivatives has been investigated using DFT the 2-hydropyridazin-3-one tautomer is typically found to be the most stable.289 

Triethylgallium has been used as a non-nucleophilic base to generate enolates from ketones, both cyclic and acyclic, without forming carbonyl addition products.290 The gallium enolates can then be C-benzoylated, and can participate in aldol reactions. Unsymmetrical ketones preferentially enolized at the methylene, under kinetic control. 

Silyl enol ethers of decalones have been synthesized which allow stereoselective protonation of the corresponding enol to be initiated and followed kinetically.291 Pendant groups have been placed so that the relative rates of intermolecular protonation and intramolecular protonation (by the proximate group) can be measured. Examples of groups which give one or other mechanism are detailed CO2- and CO2H typify the latter. 

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