Keto-enols tautomerism

When a ketone has an alpha proton, there is an interesting thing that can happen. In the presence of either acid or base, the ketone exists in equilibrium with another compound  

This other compound is called an enol, because it has a C=C bond ( ene ) and an OH group ( ol). The equilibrium shown above is actually very important, because you will see it in many mechanisms. So, let s take a closer look. 

If we focus on the connections of atoms, we wiU find that the two compounds differ from each other in the placement of one proton. The ketone has the proton attached to an alpha carbon, and the enol has the proton connected to oxygen  

It is true that the tt bond is also in a different location. But when we just focus on the atoms (which atoms are connected to which other atoms), we find that the difference is in the placement of just one proton. We have a special name to describe the relationship between compounds that differ from each other in the placement of just one proton. We call them tautomers. So, the enol above is said to be the tautomer of the ketone, and similarly, the ketone is the tautomer of the enol. The equilibrium shown above is called keto-enol tautomerism. 

Keto-enol tautomerism is NOT resonance. The two compounds shown above are NOT two representations of the same compound. They are, in fact, different compounds. These two compounds are in equilibrium with each other. 

A carbonyl compound with a hydrogen atom on its a carbon rapidly equilibrates with its corresponding enol (Section 8.5). This rapid interconversion between two substances is a special kind of isomerism known as tau-tomerism, from the Greek tauto, the same, and meros, part. The individual isomers are called tautomers. 

Note the difference between tautomers and resonance forms Tautomers are different compounds (isomers) with different structures, while resonance forms are different representations of a single structure. Tautomers hatj their atoms arranged differently, while resonance forms differ only in the position of their electrons. Note also that tautomers are rapidly interconvertible. Thus, keto and enol isomers are tautomers, but alkene isomers such as 1-butene and 2-butene are not, because they don t interconvert rapidly under normal circumstances. 

Most carbonyl compounds exist almost exclusively in the keto form at equilibrium, and it s usually difficult to isolate the pure enol. For example, cyclohexanone contains only about 0.0001% of its enol tautomer at room temperature, and acetone contains only about 0.000 000 1% enol. The percentage of end tautomer is even les.s for carbox lic acids, esters, and amides. Even though ends are difficult to isolate and are present only to a small extent at equilibrium, they are nevertheless extremely important in much of the chemistry of carbonyl compounds because they are so reactive. 

Note that only the hydrogens on the a positions of carbonyl compounds are acidic. Hydrogens at /3, y, S, and so on, are not acidic and can t be removed by base. We ll account for this unique behavior of a hydrogens shortly. 

Problem 22.1 Draw structures for the enol tautomers of the following compounds  

Aldehydes and ketones may exist as an equilibrium mixture of two forms, called the keto form and the enol form. The two forms differ in the location of a proton and a double bond. 

Write formulas for the keto and enol forms of acetone. 

PROBLEM 9.23 Draw the structural formula for the enol form of 

14b (194 ppm)] were not so characteristically different according to integration of the CDClj NMR spectrum the ratio of 14a to 14b is about 88 12. In former studies, DMSO-dg was used as the NMR solvent where only 14a and 35% of the enolized form were found. 

The tautomerism of slow keto-enol and fast enol-enol tautomeric equilibria of a number of l-(2-hydroxyphenyl)-3-naphthylpropane-l,3-diones can be easily monitored also by NMR spectroscopy, making this nucleus as suitable as and for this kind of studies [diketo form 5( 0) 469 and 548ppm, respectively enol forms 5( 0) 332 to 313 ppm (higher double bond character) and i5( 0) 156 to 135 ppm (lower double bond character)] [34]. Also computed chemical shifts were included in the analysis of the extremely fast tautomeric equilibrium of the two enol forms in asymmetric 1,3-diketones [35], for example, acetylacetone [5(C=0) 473.8 ppm 5(0-H) 191.2 ppm]. The equilibrium constants fCp thus obtained were compared with earlier experimental results based on 5( 0) in model or blocked tautomeric structures. The theoretical methodology could complement some inadequacies in experimental NMR techniques in evaluating equilibrium constants of compounds with rapid dynamic exchange [35]. 

Keto-enol tautomerism of monosubstituted phenylpyruvic acid was quantified, and both kinetic and thermodynamic aspects were discussed [46]. 

The keto-enol tautomerism of 2-nitroalkanones was restudied by NMR spectroscopy [5(0-H) 14.5-15.0ppm 5(a-CH2) 4.5-5.0ppm] and the equiHbrium constants Kp were calculated at 25 °C [48]. When employing similarly the 5(OH) signal in estimating tautomerism, it should be considered that potential moisture and acidic traces could be risky. 

Keto-enol tautomeric equilibria were further studied [49] by conventional NMR spectroscopy in self-assembled cylindrical capsules providing a nanoscale 

Carbonyl (or keto) compounds are interconvertible with their corresponding enols. This rapid interconversion of structural isomers under ordinary conditions is known as tautomerism. Keto-enol tautomerism is catalysed by acids or bases. 

This is an example of prototropy, which is the movement of an (acidic) hydrogen atom and a double bond. 

For most carbonyl compounds, the keto structure is greatly preferred, mainly due to the extra strength of the C = 0 bond. However, the enol form is stabilised if the C=C bond is conjugated with a second Jl-system or if the OH group is involved in intramolecular hydrogen bonding. Example 

Deprotonation of an ct-hydrogen atom forms an enolate ion that is stabilised by resonance (Section 1.6.3) 

Notice that the intramolecular H-bond forms a 6-membered ring 

O Protonation of the carbonyl oxygen atom by an acid catalyst HA yields a cation that can be represented by two resonance structures. 

Q Loss of H from the a position by reaction with a base A then yields the enol tautomer and regenerates HA catalyst. 

Carbonyl compounds and derivatives of vinyl alcohol exist together in an equilibrium that involves change of position of a proton and a shift of a double bond. Although the amount of enol form is immeasurably small in most aldehydes and ketones, these two forms coexist in comparable amounts when 

This phenomenon is generally described as tautomerism when rapid and reversible interchange leads to amounts of the two components of the same order of magnitude. 

Equilibrium mixtures can be converted wholly into the enolic form through the enolate, but there is no actual chemical method of bringing ketonization about—of shifting the equilibrium completely in that direction—although it can be accelerated catalytically. 

Weygand and Koch37 isolated a pure enolic form of 2-methyl-l-phenyl-1,3-butanedione as follows  

The oily 3-methyl-l-phenyl-1,3-butanedione(l g) is added to a solution of sodium (0.15 g) in methanol (3 ml), and the deep yellow solution is at once filtered and dropped into 5n-sulfuric acid (30 ml) cooled in ice-salt. The emulsion that is thus first formed must be whipped vigorously with a glass rod to cause solidification, so that most of the material becomes finely powdered and readily filterable if the oil globules once become large the product does not crystallize well and is unstable. The solid precipitate is at once filtered off, washed with very dilute hydrochloric acid, followed by ice-cold ethanol and then light petroleum, and is finally recrystallized from low-boiling light petroleum in a quartz vessel. The m.p. is 51° and the yield almost quantitative. 

Mechanism of base-catalyzed enol formation. The intermediate enolate ion, a resonance hybrid of two forms, can be protonated either on carbon to regenerate the starting keto tautomer or on oxygen to give an enol. 

Base-catalyzed enol formation occurs because the presence of a carbonyl group makes the hydrogens on the a carbon weakly acidic. Thus, a carbonyl 

I The carbonyl oxygen is protonated by an acid H-A, giving a cation with two resonance structures. 

Despite some early claims to the contrary, it was concluded in CHEC-I 84CHEC-l(3B)l that most aminopyridazines and cinnolines exist in the amino form. This generalization also extends to aminophthalazines, but 1,4-di(pyridylamino)phthalazines (29) are an exception and the presence of the imino tautomers is clearly shown by the unsymmetrical proton NMR spectrum with two distinct NH resonances, and a marked difference in the shifts of the peri benzo protons 83JHC345 . 

It may be noted that one can sometimes lose signals for nuclei due to equilibration between tautomeric forms. This is so because the signal-to-noise ratio in C-NMR spectra is sometimes poor, resulting in weak signals. If an equilibrium process is simultaneously occurring and the temperature at which 

The classical problem in the heterocychc series for the hydroxypyridine/pyridone system was discussed in Section 6.5.1.3. In the aliphatic series, the tautomeric equUibria that are mostly investigated are those for malondialdehyde and acety-lacetone, each of them possessing the critical substructure. 

In-solution NMR investigations were performed in chloroform by Bothner-By and Harris [85]. Later, Bertz and Dabbagh [86] hsted former publications in different solvents as well. These studies revealed that the s-trans enol form (28) of malondialdehyde exists in water, protic, and polar organic solvents, whereas the enol adopts the s-cis form in nonpolar solvents. Bothner-By and Harris presented a 

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Space does not permit any further detailed discussion except for a brief account of two interesting subjects. The first is concerned with keto-enol tautomerism. The classical example is ethyl acetoacetate, which can exist in the keto form (I) and the enol form (II) ... 

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... 

Enols are related to an aldehyde or a ketone by a proton transfer equilibrium known as keto-enol tautomerism (Tautomensm refers to an mterconversion between two struc tures that differ by the placement of an atom or a group)... 

A single Kekule structure does not completely descnbe the actual bonding in the molecule Ketal (Section 17 8) An acetal denved from a ketone Keto-enol tautomerism (Section 18 4) Process by which an aldehyde or a ketone and its enol equilibrate... 

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). 

The keto-enol tautomerization in the excited triplet state of 2-methylacetophenone involves the transfer of an H atom in the CHO fragment... 

Figure 1.11. NMR analysis of the keto-enol tautomerism of 2,4-pentanedione [CDCIa, 50% v/v, 25 °C, 60 MHz for H, 20 MHz for C]. (a) H NMR spectrum with integrais [resuit keto enoi = 13 87] (b) H broadband de-coupied C NMR spectrum (c) C NMR spectrum obtained by inverse gated H decoupiing with integrals [result keto enol = 15 85 ( 1)]...

Many nitrogen-containing compounds engage in a proton-transfer equilibrium that is analogous to keto-enol tautomerism ... 

The aromaticity of the pyrimidine and purine ring systems and the electron-rich nature of their —OH and —NHg substituents endow them with the capacity to undergo keto-enol tautomeric shifts. That is, pyrimidines and purines exist as tautomeric pairs, as shown in Figure 11.6 for uracil. The keto tautomer is called a lactam, whereas the enol form is a lactim. The lactam form vastly predominates at neutral pH. In other words, pA) values for ring nitrogen atoms 1 and 3 in uracil are greater than 8 (the pAl, value for N-3 is 9.5) (Table 11.1). 

Methylphenylhydrazine and both 1- and 2-naphthylhydrazines are also reported to react similarly. Phenols, in general, do not undergo this reaction, which is favoured by compounds exhibiting keto-enol tautomerism. ... 

Naphtho[2,l-h]furan-2-(3 -one 28 has been described as a keto tautomer (91JA2301). Naphtho[l,2-h]furan-3-(2//)-ones of type 29 (R = H, Me, Et, Pr, pentyl, heptyl) show keto-enol tautomerism with the enol form predominating (88RRC917). 

Armulated thiophenes of types 195 and 197 (A benzo, naphtho) were studied concerning keto-enol tautomerism. The ring fusion has a remarkable influence upon these equilibria. Whereas for the c-fused thiophenes 197 only keto tautomers were present, for h-fused derivatives 195 also the enol forms 196 were found (the equilibria are solvent dependent) (82JOC705). 

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... 

Keto-enol tautomerism of carbon) ] compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that Joses H+ from its a carbon to yield a neutral enol (Figure 22.1). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H+ to form an alkene (Section 11.10). 

Carbonyl compounds are in a rapid equilibrium with called keto-enol tautomerism. Although enol tautomers to only a small extent at equilibrium and can t usually be they nevertheless contain a highly nucleophilic double electrophiles. For example, aldehydes and ketones are at the a position by reaction with Cl2, Br2, or I2 in Alpha bromination of carboxylic acids can be similarly... 

Figure 25.8 Fructose, a ketose, is a reducing sugar because it undergoes two base-catalyzed keto-enol tautomerizations that result in conversion to an aldose.

Glucose 6-phosphate is isomerized to fructose 6-phosphate by ring opening followed by a keto-enol tautomerization. 

Reduction of the acyl phosphate gives glyceraldehyde 3-phosphate, which Q undergoes keto-enol tautomerization to yield dihydroxyacetone phosphate. 

Following hydrolysis, keto-enol tautomerization of the carbonyl group from C2 to Cl gives glucose 6-phosphate. The isomerization is the reverse of step 2 in glycolysis. 

Keto-enol tautomerism (Sections 8.4, 22.1) The rapid equilibration between a carbonyl form and vinylic alcohol form of a molecule. 

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