Organic Chemistry: Concepts and Applications - Headley Allan D. 2020
Addition Reactions Involving Carbonyls and Nitriles
9.4 Addition of Water to Carbonyl Compounds
In a similar manner, the addition of water to the carbon—oxygen double bond can be easily predicted. The general reaction showing the regiospecificity of the addition is given in Reaction (9-13).
(9-13)
As mentioned earlier, this type of addition can take place under either acidic or basic conditions. Let us look at a specific example of the addition of water and the mechanism for the formation of the product, in this case, the hydrate. The acid-catalyzed addition of water to acetone (2-proponone) is shown in Reaction (9-14).
(9-14)
Since an acidic medium has an excess of protons, the proton is added in a first step to form a protonated ketone. In the next step, the nucleophilic water adds to the electrophilic carbon of the carbonyl carbon to form a tetrahedral intermediate in which there is a formal charge of positive one (+1) on the oxygen since one pair of electrons are used from the water to form a covalent bond to the carbon atom of the protonated carbonyl compound. In the next step of the mechanism, a proton is lost to generate the neutral hydrate of acetone. Thus, the proton is a catalyst since it is used in the first step of the mechanism and regenerated in the last step.
The exact same product of Reaction (9-14) can be obtained if the conditions were basic instead of acidic. In an aqueous basic medium, there is an excess of the nucleophilic hydroxide anions, which will bond to electrophilic carbonyl carbon in the first step of the mechanism as shown in Reaction (9-15) to form a tetrahedral intermediate.
(9-15)
The initially formed tetrahedral intermediate is basic and will abstract a proton from water to form the hydrate and regenerate the catalyst, OH−. Thus, this reaction is often described as base catalyzed.
Problem 9.3
Give the hydrates that would be formed from each of the following ketones or aldehydes.
9.4.1 Reactivity of Carbonyl Compounds Toward Hydration
Depending on the groups that are bonded to the carbonyl carbon, the electrophilicity of the carbonyl carbon varies. Owing to the greater electronegativity of fluorine, compared to that of hydrogen, the positive character of the carbon of difluoroformaldehyde is greater than that of the carbonyl carbon of formaldehyde. As a result, a nucleophilic attack will be much favored for the difluoroformaldehyde, compared to formaldehyde. Thus, the equilibrium constants for the hydration of these two compounds are different. The equilibrium favors the hydrate of difluoroformaldehyde (Reaction 9-16), compared to equilibrium for the hydrate of formaldehyde (9-17). As a result, difluoroformaldehyde is more reactive than formaldehyde toward hydration.
(9-16)
(9-17)
Carbonyl compounds that have electronegative atoms and that are close to the carbonyl carbon are more reactive than comparable compounds that have electronegative groups further from the carbonyl carbon. Reactions (9-18) and (9-19) are examples that illustrate this concept.
(9-18)
(9-19)
Since the fluorine in 2-fluorobutanal is closer to the carbonyl carbon, that carbon is more electrophilic than the carbonyl carbon of 4-fluorobutanal (Reaction 9-19) in which the fluorine is further from the carbonyl carbon. The same analysis can be applied to determine the reactivity of carbonyl compounds that have groups of different electronegativities that are within the same proximity from the carbonyl carbon as shown in Reactions (9-20) and (9-21).
(9-20)
(9-21)
Due to the presence of a highly electronegative fluorine adjacent to the carbonyl compound in 2-fluorobutanal, the carbonyl carbon is very electrophilic, compared to the carbonyl carbon in 2-methylbutanal, which contains the less electronegative methyl group in the same position. Thus, the equilibrium in Reaction (9-20) lies further to the right, compared to the equilibrium in Reaction (9-21). An extension of this analysis would imply that 2,2-difluorobutanal is more reactive than 2-fluorobutanal.
The same type of analysis can be carried out to determine the relative reactivity of carbonyl compounds that have crowding around the carbonyl carbon. A more crowded carbonyl compound is less reactive than one that is not crowded. Let us consider the acid-catalyzed hydration of 2,2,4,4-tetramethyl-3-pentanone. The first step of the mechanism is shown in Reaction (9-22) where the carbonyl carbon is protonated.
(9-22)
In the next step of the reaction mechanism, the nucleophilic water attacks the protonated carbonyl to form a tetrahedral intermediate, which leads to the last step of the mechanism which involves the regeneration of the proton catalyst. These steps are shown in Reaction (9-23).
(9-23)
It becomes obvious that the tetrahedral intermediate that is formed is very crowded, hence not as stable as one that is not as crowded. You will recall that the ideal bond angle about an sp3 carbon is 109.5o. As a result, the tetrahedral intermediate is very strained and not very stable, compared to another tetrahedral intermediate that is not as crowded. Thus, a very crowded carbonyl compound is not as reactive as another that is not as crowded. The hydration of 2,2,4,4-tetramethyl-3-pentanone (Reaction 9-24) and propanone (Reaction 9-25) illustrates this concept.
(9-24)
(9-25)
Problem 9.4
i. Determine which of each of the following pairs of carbonyl compounds is more reactive toward hydration.
ii. Determine which of each of the following pairs of ketones is more reactive toward hydration.