Keto–enol tautomerism

In organic chemistry, keto–enol tautomerism refers to a chemical equilibrium between a keto form (a ketone or an aldehyde) and an enol (an alcohol). The keto and enol forms are said to be tautomers of each other. The interconversion of the two forms involves the movement of an alpha hydrogen atom and the reorganisation of bonding electrons; hence, the isomerism qualifies as tautomerism. In organic chemistry, keto–enol tautomerism refers to a chemical equilibrium between a keto form (a ketone or an aldehyde) and an enol (an alcohol). The keto and enol forms are said to be tautomers of each other. The interconversion of the two forms involves the movement of an alpha hydrogen atom and the reorganisation of bonding electrons; hence, the isomerism qualifies as tautomerism. A compound containing a carbonyl group (C=O) is normally in rapid equilibrium with an enol tautomer, which contains a pair of doubly bonded carbon atoms adjacent to a hydroxyl (−OH) group, C=C-OH. The keto form predominates at equilibrium for most ketones. Nonetheless, the enol form is important for some reactions. The deprotonated intermediate in the interconversion of the two forms, referred to as an enolate anion, is important in carbonyl chemistry, in large part because it is a strong nucleophile. Normally, the keto–enol tautomerization chemical equilibrium is highly thermodynamically driven, and at room temperature the equilibrium heavily favors the formation of the keto form. A classic example for favoring the keto form can be seen in the equilibrium between vinyl alcohol and acetaldehyde (K = / ≈ 3 × 10−7). However, it is reported that in the case of vinyl alcohol, formation of a stabilized enol form can be accomplished by controlling the water concentration in the system and utilizing the kinetic favorability of the deuterium-produced kinetic isotope effect (kH+/kD+ = 4.75, kH2O/kD2O = 12). Deuterium stabilization can be accomplished through hydrolysis of a ketene precursor in the presence of a slight stoichiometric excess of heavy water (D2O). Studies show that the tautomerization process is significantly inhibited at ambient temperatures ( kt ≈ 10−6 M/s), and the half-life of the enol form can easily be increased to t1/2 = 42 minutes for first-order hydrolysis kinetics. Another exception is the 1,3-diketones, such as acetylacetone (2,4-pentanedione), which favor the enol form. The acid catalyzed conversion of an enol to the keto form proceeds by a two-step mechanism in an aqueous acidic solution. For this, it is necessary that the alpha carbon atom (the carbon atom closest to the functional group) contains at least one hydrogen atom known as the alpha hydrogen atom. This alpha hydrogen atom must additionally be positioned such that it may line up parallel with the antibonding pi-orbital of the carbonyl group. The hyperconjugation of this bond with the C–H bond at the alpha carbon atom reduces the electron density of the C–H bond and weakens it, making the alpha hydrogen atom more acidic. When the alpha hydrogen atom is not aligned with the pi orbital, for example in the adamantanone or other polycyclic ketones, the enolization is impossible or very slow. In the first step of the mechanism, the exposed electrons of the C=C double bond of the enol are donated to a hydronium ion (H3O+). This addition follows Markovnikov's rule, thus the proton is added to the carbon atom with more attached hydrogen atoms. This is a concerted step with the oxygen atom in the hydroxyl group donating electrons to produce the eventual carbonyl group. One of the early investigators into keto–enol tautomerism was Emil Erlenmeyer. His Erlenmeyer rule, developed in 1880, states that all alcohols in which the hydroxyl group is attached directly to a double-bonded carbon atom become aldehydes or ketones. This conversion occurs because the keto form is, in general, more stable than its enol tautomer. The keto form is therefore favored at equilibrium because it is the lower energy form. If R1 and R2 (note equation at top of page) are different substituents, there is a new stereocenter formed at the alpha position when an enol converts to its keto form. Depending on the nature of the three R groups, the resulting products in this situation would be diastereomers or enantiomers.