Question

The Williamson ether synthesis involves treatment of a haloalkane with a metal alkoxide. Following are two reactions intended to give benzyl tert-butyl ether. One reaction gives the ether in good yield and the other reaction does not. Which reaction gives the ether? What is the product of the other reaction, and how do you account for its formation? (a) C C ( C ) ( C ) C (b) X c 1 c c c ( C O C ( C ) ( C ) C

Short answer

Answer: The reaction between benzyl chloride and tert-butoxide gives benzyl tert-butyl ether in good yield. The unsuccessful reaction between tert-butyl chloride and phenoxide produces isobutylene instead.

Step-by-step solution

Identify the target ether and starting materials

The target molecule is benzyl tert-butyl ether. To form this ether, we would need two possible combinations of starting materials: 1. Benzyl chloride (a haloalkane) and tert-butoxide (an alkoxide) 2. tert-Butyl chloride (a haloalkane) and phenoxide (an alkoxide, derived from phenol) Now, let's analyze both reactions.

Evaluate the formation of benzyl tert-butyl ether in Reaction 1

In the first reaction, we have benzyl chloride reacting with tert-butoxide. The Williamson ether synthesis mechanism involves a nucleophilic attack of the alkoxide on the haloalkane. It comprises of an SN2 reaction in which the alkoxide acts as the nucleophile, and the haloalkane acts as the electrophile. In this case, tert-butoxide is a bulky nucleophile, and benzyl chloride is a primary halide. The reaction between them should proceed with the sn2 mechanism, to give the desired benzyl tert-butyl ether.

Evaluate the formation of benzyl tert-butyl ether in Reaction 2

In the second reaction, we have tert-butyl chloride reacting with phenoxide. tert-Butyl chloride is a tertiary halide, which is unlikely to undergo an SN2 mechanism due to steric hindrance. Since the Williamson ether synthesis relies on the SN2 mechanism, it won't work well in this case. The reaction might instead undergo an E2 elimination mechanism, leading to the formation of a different product, like an alkene.

Determine the successful reaction and the product of the unsuccessful reaction

Based on the analysis in Steps 2 and 3, we can conclude that Reaction 1 will give benzyl tert-butyl ether in good yield. This is because the reaction between benzyl chloride and tert-butoxide proceeds via the SN2 mechanism as required for the Williamson ether synthesis. On the other hand, Reaction 2 does not give benzyl tert-butyl ether. The reaction between tert-butyl chloride and phenoxide most likely proceeds via the E2 elimination mechanism instead, leading to the formation of an alkene product. In this case, the alkene would be isobutylene. In conclusion, the Williamson ether synthesis involving the treatment of benzyl chloride with tert-butoxide gives benzyl tert-butyl ether in good yield. The other reaction gives isobutylene due to the E2 elimination mechanism.

Key concepts

Haloalkane and Metal Alkoxide Reaction

The Williamson ether synthesis is a classic organic chemistry reaction involving haloalkanes and metal alkoxides to produce ethers. When a haloalkane (a compound containing a halogen attached to an alkane) reacts with a metal alkoxide (a metal ion bonded to an alkoxide ion), an ether is formed through a nucleophilic substitution mechanism.

For the reaction to be successful, the choice of haloalkane is critical. Primary haloalkanes are ideal because they are less hindered, allowing the alkoxide nucleophile better access to the electrophilic carbon atom. In contrast, tertiary haloalkanes are often not suitable for this reaction due to steric hindrance which prevents the nucleophile from attacking the electrophilic carbon effectively.

Steric hindrance refers to the difficulty caused by the size of groups within a molecule, slowing down or preventing certain reactions. In the context of the exercise, tert-butoxide, a bulky nucleophile, reacts well with benzyl chloride (a primary haloalkane), facilitating the ether formation. However, tert-butyl chloride (a tertiary haloalkane) is hindered, making it unsuitable for the desired substitution reaction.

SN2 Reaction Mechanism

The SN2 reaction mechanism is a type of nucleophilic substitution where 'SN' stands for nucleophilic substitution and '2' denotes the bimolecular nature of the reaction. This implies that the rate of the reaction depends on the concentration of both the nucleophile and the electrophile.

In this mechanism, the nucleophile attacks the electrophilic carbon atom from the opposite side of the leaving group, resulting in a backside attack. This leads to an inversion of configuration at the carbon center, resembling an umbrella turning inside out. The reaction proceeds in a single step, without any intermediates, as the bond formation with the nucleophile and bond breaking of the leaving group occur simultaneously.

An ideal SN2 reaction requires a strong nucleophile, such as a metal alkoxide, and a less sterically hindered (generally primary) haloalkane. Benzyl chloride and an alkoxide form benzyl tert-butyl ether through the SN2 mechanism effectively because the primary halide and the nucleophile's reactivity are well-suited for this type of reaction.

E2 Elimination Mechanism

The E2 elimination mechanism stands for 'Elimination Bimolecular,' indicating that the reaction's rate depends on the concentrations of both the base and the substrate. During an E2 reaction, the base removes a proton (hydrogen ion) from the substrate, while the halide (leaving group) also leaves, resulting in the formation of a pi bond—a double bond between the adjacent carbon atoms.

This elimination mechanism often competes with SN2 reactions, particularly when sterically hindered tertiary haloalkanes are involved. In the educational exercise, tert-butyl chloride is more likely to undergo E2 elimination due to its tertiary structure, producing an alkene such as isobutylene. Factors favoring the E2 mechanism include a strongly basic nucleophile, high steric hindrance of the substrate, and typically a higher reaction temperature.

Understanding both the SN2 and E2 mechanisms is crucial in predicting the outcome of reactions involving haloalkanes and nucleophiles/bases. Knowledge of these mechanisms allows students to not only interpret the reactions but also design synthetic pathways for creating desired products efficiently.