On keto-enol tautomerism

In the free state and in their reactions the simple aldehydes and ketones are in general known only in the aldo- and keto-forms. Erlen-meyer suggested the rule that the isomeric enol-structure, which might be formed at first in the production of acetaldehyde from glycol, for example, should in no case be capable of existence. 

Chiefly as a result of the work of Claisen, this rule has been proved to be erroneous. We know now that even simple aldehydes and ketones exhibit a detectable tendency to enolise , by the wandering of an H-atom and the simultaneous shift of a double bond. 

Thus it has been possible to show that in the bromination of acetone, a process which has been found to be unimolecular, not the normal keto-form, but the tautomeric enol-form reacts. The enol-form is present, in equilibrium with the keto-form, in amount too small to be measured. As soon as this amount has reacted a further quantity is formed and the process is repeated. That the reaction is unimolecular follows from the fact that it is the rate of rearrangement (I) which is measured, whilst the reaction of the enol with bromine (II) takes place with immeasurable rapidity (Lapworth). 

It may be mentioned here that, if water is excluded, acetone and also 

The Mechanism of the Ethyl Acetoacetate Synthesis—Before the tautomerism of ethyl acetoacetate is discussed we must consider the mechanism of its formation, which for decades has been the subject of lively discussion and was conclusively explained only in recent years (Scheibler). It has been found that even the C=0-group of the simple carboxylic esters, although in other respects inferior in activity to the true carbonyl group, can be enolised by alkali metals. Thus ethyl acetate is converted by potassium into the potassium salt of the tautomeric enol with evolution of hydrogen  

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At the end of the war, he returned to Munich as Associate Professor and Director of the Laboratory of Organic Chemistry. The Department was then under Richard Willstatter s direction, and Meyer occupied the same position as the one held for many years by Willstatter under Baeyer s leadership. He resumed his investigation on keto-enol tautomerism, and, in collaboration with H. Hopff, isolated by distillation the pure enol form of ethyl acetoacetate. Other work from the same period included an examination of the action of nitric acid on phenol and phenol ether (with W. Reppe and W. E. Elbers), and a study of narcosis (with H. G. Billroth)— an extension of his father s work. 

Scheme 1.3 The effect of solvent polarity on keto-enol tautomerization of ethyl acetoacetate...

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. 

Bertolasi, V., Ferretti, V., Gilli, P., etcd. (2008) Substituent effects on keto-enol tautomerization of fS-diketones from X-ray structural data and DFT calculations. New Journal of Chemistry, 32, 694-704. 

In 1906, at the age of twenty-nine, Hibbert came to the United States on a two-year appointment at Tufts College, in Boston, Massachusetts. There he worked under Professor Arthur Michael on keto-enol tautomerism and the effect of solvent on the equilibrium. Hibbert s association with Michael, with whom he published some half-dozen papers, was to have a profound and lasting influence on his subsequent career,... 

Ferrari, E., Saladini, M., Pignedoli, F., Spagnolo, F., and Benassi, R. (2011) Solvent effect on keto-enol tautomerism in a new 3-diketone a comparison between experimental data and different theoretical approaches. New J. Chem., 35, 2840-2847. 

Hydroxyquinolines (Quinolinols). A number of methods have been employed for their preparation. A modified Chichibabia reaction of quinoline ia fused KOH—NaOH at 240°C produces 70% of 2-hydroxyquiQoline [59-31-4] (121). Alternative names based on the facile keto—enol tautomerism of two of these compounds are 2(1H) and 4(lJd)-quiQolinone none of the other quinolinols show this property. The treatment of... 

The keto-enol tautomerism of 1,2-benzisoxazoles has been examined and the existence of either form can be postulated on the basis of reactivity. IR analysis on the solid indicates the exclusive existence of the enol form, while in CHCI3 solution both appear to be present (71DIS(B)4483). 

Interestingly, the product actually isolated from alkyne hydration is not the vinylic alcohol, or enol (ene + ol), but is instead a ketone. Although the enol is an intermediate in the reaction, it immediately rearranges to a ketone by a process called keto-enol tautomerisni. The individual keto and enol forms are said to be tautomers, a word used to describe constitutional isomers that interconvert rapidly. With few exceptions, the keto-enol tautomeric equilibrium lies on the side of the ketone enols are almost never isolated. We ll look more closely... 

A carbonyl compound with a hydrogen atom on its a carbon rapidly equilibrates with its corresponding enol (Section 8.4). This rapid interconversion between two substances is a special kind of isomerism known as keto-enol tautomerism, from the Greek Canto, meaning "the same," and meros, meaning "part." The individual isomers are called tautomers. 

In addition to heterocycles, other molecular systems have attracted theoretical attention with respect to prediction of tautomeric equilibria and solvation effects thereon. The most commonly studied example in this class is the equilibrium between formamide and formamidic acid, discussed in the next section. In addition, some continuum modeling of solvation effects on keto/enol equilibria have appeared these are presented in section 4.2.2.2. We note that the equilibrium... 

The last step of the reaction is the keto-enol tautomerization from T 4-cyclohexadienone intermediates (15) to aromatic products (16). Such a step is accompanied with a considerable gain in energy about 80 kJ mol 1 for vinylcarbenes [29], (where a phenol system is formed by the tautomerization step), and about 175 kJ mol 1 for phenylcarbenes [25] (where a naphtol system is produced). The energy barrier for such step should be lower than 40 kJ mol 1 according to previous calculations on similar systems [42],... 

Like reaction rates, the effect of solvent polarity on equilibria may be rationalized by consideration of the relative polarities of the species on each side of the equilibrium. A polar solvent will therefore favour polar species. A good example is the keto-enol tautomerization of ethyl acetoacetate, in which the 1,3-dicarbonyl, or keto, form is more polar than the enol form, which is stabilized by an intramolecular H-bond. The equilibrium is shown in Scheme 1.3. In cyclohexane, the enol form is slightly more abundant. Increasing the polarity of the solvent moves the equilibrium towards the keto form [28], In this example, H-bonding solvents will compete with the intramolecular H-bond, destabilizing the enol form of the compound. 

The mixture of quinone methides initially formed by combination of the coniferyl radicals in their various mcsomeric forms, i.e. (I), (III), (V), (IX) and others, can be detected by means of their characteristic spectrum with a maximum at about 312 mp (52) the haU-hfe of the mixture in 70 % aqueous dioxan is 1 hour. Those quinone methides that can rearomatize by keto-enol tautomerism, e.g. (IX), or intramolecular additions, e.g. (I) or (III) may become stabilized faster than those of type (V) which rely on addition of a foreign molecule. The quinone methides that rearomatize intramolecularly appear to react exclusively in this way, probably by a concerted mechanism that represents collapse of the activated transition state. 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

This is achieved by two keto-enol tautomerism reactions and a common enol (see Box 10.1). Mechanistically, it is identical to the isomerization of glucose 6-phosphate to fructose 6-phosphate seen earlier in the sequence, so we can move on to the next step of the pathway. 

On the one hand. Rueping s protocol involved a combination of chiral BINOL phosphate (R)-3j (10 mol%, R = 2-naphthyl) bearing 2-naphthyl substituents and achiral acetic acid (20 mol%) [62], While stronger Brpnsted acid 3j is expected to activate electrophile 86, the weaker Brpnsted acid is proposed to facilitate the keto-enol tautomerism of nucleophile 101 (Scheme 40). On the other hand, Gong... 

X,Y=0,S,Se,Te], has been undertaken.628 The stabilities of different tautomeric forms of 4-hydroxycoumarins have been evaluated629 by MNDO calculations, and the four lowest-energy oxo-hydroxy tautomers of 5-fluorouracil have been studied630 using density functional methods. Semiempirical calculations have been carried out on the keto-enol tautomerism of triazolopyrimidines.631 A base-catalysed keto-enol tautomer-ism has been proposed632 to be responsible for the observed deuterium exchange of the hydrogens at the 3-position of diazepam when the molecule is treated with alkaline deuteriated methanol. 

Pterins belong to a family of nitrogen heterocyclic compounds and consist of 2-amino-4-hydroxypteridine. Due to keto-enol tautomerism (Eq. 1), pterin exists generally as the 4-keto, i.e. amido, form that is illustrated as 2-aminopteridin-4(3H)one (4) rather than the enol form (3). Various pterin derivatives have been unexceptionally isolated from almost all kinds of living organisms and almost all such pterin derivatives have carbon substituents on the C(6) position. 

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. 

Tautomerism is an extremely solvent-dependent chemical process which affects the chemical properties of molecules. A well known example is the keto-enol equilibrium of (3-diketones, in which the enol form is the most populated species in apolar solvents, whereas the keto species is the most stable tautomer in aqueous solution [70], Another classical example is the solvent influence on the keto-enol tautomerism of 4-pyridone, where the population ratio between the keto and enol tautomers changes by a factor of 104 upon its transfer from the gas phase to an aqueous solution [71]. 

When a terminal alkyne is treated with an excess of hydrogen halide the halogens both end up on the more substituted carbon (Fig. F). This is in accordance with the Markovnikov s rule which states that the additional hydrogens end up on the carbon which already has the most hydrogens. The same rule applies for the reaction with acid and mercuric sulphate which means that a ketone is formed after keto-enol tautomerism instead of an aldehyde (Fig. G). 

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