Carbonyl compounds tautomers

Carbanions derived from carbonyl compoimds are often referred to as etiolates. This name is derived from the enol tautomer of carbonyl compounds. The resonance-stabilized enolate anion is the conjugate base of both the keto and enol forms of carbonyl... 

The study of the chemistry of carbonyl compounds has shown that they can act as carbon nucleophiles in the presence of acid catalysts as well as bases. The nucleophilic reactivity of carbonyl compounds in acidic solution is due to the presence of the enol tautomer. Enolization in acidic solution is catalyzed by O-protonation. Subsequent deprotonation at carbon gives the enol ... 

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. 

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 enol tautomer is even less for carboxylic acids, esters, and amides. Even though enols are difficult to isolate and are present only to a small extent at equilibrium., they are nevertheless responsible for much of the chemistry of carbonyl compounds because they are so reactive. 

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... 

Whilst reactions of a, -unsaturated carbonyl compounds with 2 have been the subject of a number of studies, the corresponding reactions of their enolic tautomers have received little attention. Reaction of the /S-hydroxy-a, /i-unsaturated ketones... 

The Mannich reaction is best discussed via an example. A mixture of dimethylamine, formaldehyde and acetone under mild acidic conditions gives N,N-dimethyl-4-aminobutan-2-one. This is a two-stage process, beginning with the formation of an iminium cation from the amine and the more reactive of the two carbonyl compounds, in this case the aldehyde. This iminium cation then acts as the electrophile for addition of the nucleophile acetone. Now it would be nice if we could use the enolate anion as the nucleophile, as in the other reactions we have looked at, but under the mild acidic conditions we cannot have an anion, and the nucleophile must be portrayed as the enol tautomer of acetone. The addition is then unspectacular, and, after loss of a proton from the carbonyl, we are left with the product. 

Heterocyclic methylene-active carbonyl compounds (or their tautomers) with arylidenemalononitriles yield 2-amino-4H-pyrans condensed with... 

Another possible mechanism for this reaction was suggested by Dr. G.R. Krow (private communication), this one involving a a bona fide a-amino nitrite ester as an intermediate. If the qumone monoxime tautomer of the nitrosophenol were reacting as an electrophilic carbonyl compound with the amine according to Fig. 3, the resulting immonium ion, VII, could attack nitrite to yield the nitrosamine via intermediate Ih with regeneration of the nitrosophenol. This proposal is summarized in Fig. 9. 

Ring Carbonyl Compounds and their Hydroxy Tautomers 3.3.2.5.1 Survey of structures... 

Hydrolytic replacement of a fluorine attached to a C = C bond by a hydroxy group leads to the hydroxy compound or its tautomeric carbonyl compound. For example, 2,3,3,4,4,4-hexa-fluoro-l-(phenyldiazenyl)but-l-ene (7) is hydrolyzed in acidic media to give the phenyl-hydrazone in a mixture with its tautomer.13... 

The second main aspect of reactions of carbonyl compounds is one we have already touched upon in Chapter 3. The carbonyl group increases the acidity of C—H bonds on a carbon directly attached to it by many powers of ten over an unactivated carbon-hydrogen bond. Removal of such a proton leaves the conjugated ambident enolate ion (29), which can be reprotonated either at the carbon, to give back the original keto tautomer, or at oxygen to give the enol (Equation 8.61).135 Acid also promotes interconversion between enol and keto... 

Because acid conditions are used so this process does not involve an enolate ion. Instead, the reaction occurs through the enol tautomers of the carbonyl compound. The enol tautomer acts as a nucleophile with a halogen by the mechanism shown below. In the final step, the solvent acts as a base to remove the proton. 

Fig. 12.16. Electrophilic functionalization of carbonyl compounds A, whose enol tautomer is unsuitable or unavailable at sufficient concentration, via the related enamines D a survey of mechanistic details and important intermediate products.

Section 11.6 discussed the acid-catalyzed addition of water to alkynes. The initial product of this reaction, called an enol, has a hydroxy group attached to one of the carbons of a CC double bond. The enol is unstable and rapidly converts to its tautomer, a carbonyl compound. The carbonyl and enol tautomers of acetone are shown in the following equation ... 

Anhydro-4-hydroxyoxazoIium hydroxides, such as compound (231), behave as carbonyl ylides (232) in cycloaddition reactions, yielding bicyclic adducts with alkenes and carbonyl compounds (Scheme 24). The adducts produced by combination with alkynes fragment spontaneously in a retro-Diels-Alder reaction, giving furans (equation 57). The formation of a furan by the action of DMAD on the 4(5//)-oxazolone (233) shows that the latter exists in equilibrium with the mesoionic tautomer (234 equation 58) (79JOC626). 

The enol rather than the keto tautomer is the intermediate leading to the ketohydroperoxide form (through autoxidation). The catalytic effectiveness of carbonyl compounds would therefore be expected to be directly proportional to their degree of enolization and the reactivity of their enol forms. 

In contrast to kinetic data, thermodynamic data on enol and enolate formation are far more scarce. This results from the usually very low enol and enolate stabilities which, at equilibrium, make it difficult to measure their proportions relative to the carbonyl compound. This section deals with available data on keto-enol equilibria as well as on acidity constants of the two tautomers. 

Ring Carbonyl Compounds and their Hydroxy Tautomers... 

Draw keto-enol tautomers of carbonyl compounds, identify acidic hydrogens, and draw the resonance forms of enolates. 

Baae-catalyzed enol Formation occurs by an acid-base reamion between catalyst and carbonyl compound. The carbonyl compound acta as a weak protre acid and donates- one of its e. The rss-uJtant anion—an enolatc ion —is then reprotonated to yield a neutral compound. Since the enolate iun is a resonance hybrid of two forms, it can be proto-nated either on the or carbon to regenerate the keto tautomer or on oxygen to give the enol tautomer (Figure 22.2, p, 905). 

In line with the mechanistic results from above and from the oxidation of stable enols (Sect. 3.1), the following mechanism was postulated (Scheme 8). Considering the multistep nature of the mechanism it is obvious that several, sometimes conflicting requirements have to be accomodated in the reaction system to maximize yields. For example, the redox potential of the oxidant has to be low in order to avoid dir rt oxidation of the carbonyl compound, but should still allow oxidation of the enol tautomer. In this case the chosen oxidant may turn out to be too weak for fast oxidation of the a-carbonyl radical intermediate, and as a consequence only radical reactions will be triggered. 

The Claiscn rearrangement of allyl vinyl ethers is usually an irreversible reaction due to the energetic benefit of forming aC-O double bond. However, in strained bicyclic systems the retro-Claisen rearrangement (3-oxa-Cope rearrangement) of y,<5-unsaturated aldehydes has been observed32. Sometimes equilibrium mixtures of vinyl ether and carbonyl compound were found. For example, the ratio of the valence tautomers, bicyclo[3.1.0]hex-2-ene-6-cWo-methanal to 2-oxabicyclo[3.2.l]octa-3,6-diene, is approximately 7 333. Nevertheless this reaction was used in the preparation of a key intermediate in a prostacyclin synthesis34. 

Let s first examine the conversion of a general enol A to the carbonyl compound B. A and B are called tautomers A is the enol form and B is the keto form of the tautomer. 

Recall from Chapter 11 that the keto and enol tautomers of a carbonyl compound are in equilibrium, but the keto form is lower in energy, so it is highly favored in most cases. 

The mechanism of this reaction involves the formation of an amide tautomer. Two tautomers can be drawn for any carbonyl compound, and those for a 1° amide are as follows ... 

The imidic acid and amide tautomers are interconverted by treating with acid or base, analogous to the keto-enol tautomers of other carbonyl compounds. In fact, the two amide tautomers are exactly the same as keto-enol tautomers except that a nitrogen atom replaces a carbon atom bonded to the carbonyl group. 

---