Question

Attempted Grignard reaction of cyclohexanone with tert-butylmagnesium bromide yields only about \(1 \%\) of the expected addition product along with \(99 \%\) unreacted cyclohexanone. If \(D_{3} \mathrm{O}^{+}\) is added to the reaction mixture after a suitable period, however, the "unreacted" cyclohexanone is found to have one deuterium atom incorporated into it. Explain.

Short answer

The steric hindrance of tert-butylmagnesium bromide inhibits the Grignard reaction, but D3O+ causes deuterium incorporation by proton exchange.

Step-by-step solution

Identify Reaction Mechanism

The reaction in question is a Grignard reaction, where an organometallic compound, tert-butylmagnesium bromide, acts as a nucleophile and attacks the carbon of the carbonyl group in cyclohexanone.

Analyze Steric Hindrance

Tert-butyl groups are large and bulky, creating significant steric hindrance. This makes it difficult for the tert-butylmagnesium bromide to effectively attack the carbonyl carbon in cyclohexanone, leading to only about 1% successful reaction and limiting the formation of the expected addition product.

Consider Reaction Inhibition

Due to steric hindrance and potential electronic effects, the Grignard reagent interacts very little with the carbonyl carbon, resulting in cyclohexanone largely remaining unreacted.

Role of D3O+ Addition

Adding D3O+ to the reaction mixture results in an acidic environment. The unreacted Grignard reagent, tert-butylmagnesium bromide, is sensitive to acidic conditions and reacts with D3O+.

Protonation and Deuterium Exchange

In the presence of D3O+, a proton (or deuteron in this case) transfer can occur with cyclohexanone, leading to the exchange of a proton for a deuteron in the alpha position relative to the carbonyl group of the cyclohexanone.

Conclusion

Thus, although the Grignard reagent does not add to the carbonyl carbon in most cases, it can facilitate protonation when D3O+ is added, resulting in the incorporation of deuterium in the cyclohexanone.

Key concepts

Organometallic Compounds

Organometallic compounds like tert-butylmagnesium bromide are unique and important in chemistry. They consist of a metal atom bonded to carbon. In the Grignard reaction, the organometallic compound acts as a nucleophile, seeking out positively charged or electron-deficient areas to interact with. These compounds form the basis for many vital chemical transformations and are particularly sensitive to the specific conditions of their reactions.
- Key players in carbon-carbon bond formation.
- Often used as nucleophiles in reactions with carbonyl groups.
- Require careful handling as they react swiftly with water or air. Their reactivity is what makes Grignard reagents useful but also challenging to work with. Their sensitivity to sterics and electronics in a molecule, such as bulky groups or electron-withdrawing effects, can significantly influence the course of a reaction.

Steric Hindrance

Steric hindrance refers to the impediment to chemical reactions caused by the physical size of groups within molecules. - Occurs when bulky groups surround a reactive center.
- Can prevent nucleophiles from approaching or interacting with the target atom. In the case of the Grignard reaction with tert-butylmagnesium bromide, the large, space-occupying tert-butyl group creates a barrier around the magnesium center.
This makes it challenging for the organometallic compound to effectively reach and react with the carbonyl carbon of cyclohexanone. As a result, the reaction yield is very low (about 1%).
Understanding steric hindrance is crucial for predicting and controlling the outcomes of organic reactions, as it often dictates whether a reaction will proceed or not.

Carbonyl Chemistry

Carbonyl chemistry is a fascinating area focusing on reactions involving carbonyl groups, characterized by a carbon double-bonded to an oxygen atom (C=O).
These groups are highly polar, with the carbon atom partially positive and the oxygen atom partially negative. - Carbonyls are important in forming many products through addition reactions.
- Reactivity varies with different substituents on the carbonyl carbon. In the attempted Grignard reaction with cyclohexanone, the carbonyl carbon is the target of attack by the organometallic compound. However, steric hindrance and other factors, such as electronic effects, can thwart this interaction.
Exploring carbonyl chemistry involves understanding how these groups can be manipulated to create new bonds, essential for building more complex molecules.

Deuterium Exchange

Deuterium exchange is a process used to investigate reaction mechanisms by replacing hydrogen atoms with deuterium, a heavier isotope of hydrogen.
In the experiment with cyclohexanone, when D3O+ is introduced, it provides deuterons (D+ ions) in the mixture.
- In acidic environments, deuterium can exchange with hydrogens, especially those in the alpha position relative to carbonyl groups. Although the main Grignard reaction product is not significantly formed due to steric hindrance, the cyclohexanone can still undergo deuterium exchange in the presence of D3O+. Here, the cyclohexanone molecule incorporates a deuterium atom, altering its structure slightly.
Deuterium exchange is invaluable for researchers wanting to track changes in a molecule and study the dynamics of reactions more deeply.