Keto-enol isomers

The aldehyde or ketone is called the keto form and the keto enol equilibration referred to as keto-enol isomerism or keto-enol tautomerism Tautomers are constitu tional isomers that equilibrate by migration of an atom or group and their equilibration IS called tautomerism The mechanism of keto-enol isomerism involves the sequence of proton transfers shown m Figure 9 6... 

The compounds 2- (16) and 4-pyridone (38) undergo chlorination with phosphoms oxychloride however, 3-pyridinol (39) is not chlotinated similarly. The product from (38) is 4-chloropyridine [626-61-9]. The 2- (16) and 4-oxo (38) isomers behave like the keto form of the keto—enol tautomers, whereas the 3-oxo (39) isomer is largely phenolic-like, and fails to be chlotinated (38). 

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. 

After succeeding in the asymmetric reductive acylation of ketones, we ventured to see if enol acetates can be used as acyl donors and precursors of ketones at the same time through deacylation and keto-enol tautomerization (Scheme 8). The overall reaction thus corresponds to the asymmetric reduction of enol acetate. For example, 1-phenylvinyl acetate was transformed to (f )-l-phenylethyl acetate by CALB and diruthenium complex 1 in the presence of 2,6-dimethyl-4-heptanol with 89% yield and 98% ee. Molecular hydrogen (1 atm) was almost equally effective for the transformation. A broad range of enol acetates were prepared from ketones and were successfully transformed into their corresponding (7 )-acetates under 1 atm H2 (Table 19). From unsymmetrical aliphatic ketones, enol acetates were obtained as the mixtures of regio- and geometrical isomers. Notably, however, the efficiency of the process was little affected by the isomeric composition of the enol acetates. 

In this context, 14 different reaction conditions were investigated in 14 hours. By software-supported process optimization (factorial design), the initial yield of 49% could be improved to 78% with a simultaneous increase in keto/enol isomer ratio (A B) of65 35 to95 5. 

N. Blechta et al. [63] used LC-NMR experiments with H- Si indirect detection to analyze mixtures of siloxan polymers. Other studies take advantage of the unique ability of NMR to study dynamic processes like isomerization, for example, the interconversion of rotational isomers or enol-keto tautomers [64,65]. 

All the isomers 27-31 of benzoxazinotropone are subject to keto-enol tautomerism (Figure 4), which was proven by their O-acetylation. However, the keto forms were predicted to be favored energetically by calculations using the... 

Structural isomers existing in rapid equilibrium are tautomers and the equilibrium reaction is tautomerism. The above is a keto-enol tautomerism. 

Many simple organic compounds exist as mixtures of two or more rapidly interconvertible isomers or tautomeric forms. Tautomers can sometimes be separated one from the other at low temperatures where the rate of interconversion is low. The classic example is the oxo-enol (or keto-enol) equilibrium (Eq. 2-1). 

Unlike phenols (Section 26-l), structural analysis of many of the hydroxy-substituted aza-aromatic compounds is complicated by isomerism of the keto-enol type, sometimes called lactim-lactam isomerism. For 2-hydro xypyrimidine, 19, these isomers are 19a and 19b, and the lactam form is more stable, as also is true for cytosine, 15, thymine, 16, and the pyrimidine ring of guanine, 18. 

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. 

Yoshino (51) studied the abundance ratios of the gauche and trans forms of dichloroethane and the keto-enol isomers of acetyl acetone when these compounds were adsorbed (less than monolayer quantities) on silica gel. The gauche-trans ratio, which is unity in chloroform solution and 1.4 in the pure liquid, was found to be 1.9 in the adsorbed state. The 1430-cm.-1 gauche band and the 1450-cm.-1 trans band were not affected by the adsorption. The absorption bands of acetyl acetone were measured for a 1.5 % chloroform solution, the pure liquid, liquid saturated with water, and the adsorbed state. The relative intensity of the 1600-cin. 1 enol band and the 700-cm.-1 keto baud were used to determine the isomer ratio. The 1600-... 

The above examples show that proton transfer resulting in keto-enol tau-tomerism cannot be studied separately from the environment. The equilibrium between keto and enol forms, both in solution and in the solid state is a derivative of numerous noncovalent interactions that can stabilize a particular isomer. In this context, host-guest chemistry can shed more light towards understanding of the proton-transfer mechanism in biological systems. 

However, carbacepham derivatives 179 and 180 could be generated from 178 by Jones oxidation to furnish a mixture (10 90) of keto-enol isomers 179 and 180, which can be methylated using diazomethane to give 181 in 63% yield (Scheme 24). Evaluation of various carbacepham analogues as well as carbapenam analogues indicated that some are promising potent antibiotics. 

The initial product has a hydroxy group attached to a carbon-carbon double bond. Compounds such as this are called enols (ene + ol) and are very labile—they cannot usually be isolated. Enols such as this spontaneously rearrange to the more stable ketone isomer. The ketone and the enol are termed tautomers. This reaction, which simply involves the movement of a proton and a double bond, is called a keto—enol tautomerization and is usually very fast. In most cases the ketone is much more stable, and the amount of enol present at equilibrium is not detectable by most methods. The mechanism for this tautomerization in acid is shown in Figure 11.6. The mercury-catalyzed hydration of alkynes is a good method for the preparation of ketones, as shown in the following example ... 

The term keto enol tautomerism implies two isomers and for most purposes this simple view is adequate. However for a symmetric /3-diketone, RCOCH2COR, or for MDA, HCOCH2COH, there are three diketo conformers and six enol ones, assuming that is, that the skeletal framework of oxygens and carbon atoms is planar Fig. 2. For an asymmetric /3-diketone or /3-ketoaldehyde this increases to four and eleven respectively since it is possible to distinguish the various conformers of RC(OH)=CHCOR from those of RCOCH=C(OH)R. The same is true of symmetric /J-thioketones, RCSCH2COR. 

Because the system exists essentially completely as the thiol isomer, a carbon-acid acidity constant for ionization starting with the thio-keto form as the initial state, QJ, could not be measured, and a keto-enol equilibrium constant, ATe, could not be determined. A lower limit for can nevertheless be estimated on the assumption that 5% of the keto isomer would have produced a detectable signal in the H NMR spectrum of the enol form. Because no such signal was seen, must be greater than 20, which makes pK less than —1.3. The relationship = KeQJ then leads to > 1.1 x 10 M, pQ <2.1. 

Tautomers are Isomers in which the site of a hydrogen atom and a double bond are different, The tautorTiers are in dynamic equilibrium with each other. We have already rnet keto-enol taufomerism, of which this is a variation, in Chapter 6, Imine-enaiTiine taufomerism is another example ... 

In many of these cases, both the enolate anion and substrate can exist as (Z) or (E) isomers. With enolates derived from ketones or carboxylic esters. The (E) enolates gave the syn pair of enantiomers (p. 166), while (Z) enolates gave the anti pair. Nitro compounds add to conjugated ketones in the presence of a dipeptide and a piperazine. ° Malonate derivatives also add to conjugated ketones, and keto esters add to conjugated esters.Addition of chiral additives to the reaction, such as metal-salen complexes,proline derivatives, or (—)-sparteine, ... 

Tautomerism Isomerism in which isomers, called tautomers, are readily interconvertible. Keto-enol tautomerism is an example... 

When two constitutional isomers are present in a rapidly established equilibrium, the two molecular types are designated tautomers and the phenomenon tautomerism. Tautomers differ in the position of a double bond and a flexible group. For the keto-enol tautomerism, the tautomeric forms are the keto and the enol form. Mostly, the equilibrium is on the left hand side. 

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