Chapter 13, Problem 13.33P

Interpretation Introduction

(a)

Interpretation:

It is to be determined whether the solvent would interfere with producing the intended target in the proposed synthetic step. For those that would, another solvent that can be used is to be suggested with an explanation.

Concept introduction:

Solvent plays an important role in the proposed synthetic step by not interfering with the reactant molecule or intermediates. For E2 elimination reactions, a strong base is used in the presence of a polar aprotic solvent to yield the most substituted alkene is the major product. The requirement of the solvent for E2 reactions is aprotic, as aprotic solvents do not solvate the anions (negatively charged ions) as strongly as they solvate cations (positively charged ions). If the base used in the reaction and the base produced by the deprotonation of solvent molecules is the same, then the reaction proceeds in the forward direction and the proposed synthetic step is valid and acceptable. If the base used in the reaction is different from the base produced by the deprotonation of solvent molecules, then they would compete and the proposed synthetic route then would not be the valid route.

Answer to Problem 13.33P

The solvent for the proposed synthetic step is appropriate. The proposed synthetic step is an example of an E2 reaction, which favors the Zaitsev product (most substituted alkene). If the solvent ethanol is deprotonated, the result is still an ethoxide ion which is the same base that is already shown.

Explanation of Solution

The given proposed synthetic step is:

The reactant molecule has a good leaving group, $\text{-OTs}$. The reagent used in this step is sodium ethoxide which is a source of ethoxide ions and a good nucleophile as well as a good base. The product molecule is the alkene, this indicates that the reaction type is an elimination reaction, E2. An E2 elimination reaction needs a good base and an aprotic solvent. The solvent in the given step is ethanol, which is a polar protic solvent. But, sodium ethoxide in ethanol would produce ethoxide ions, ${\text{-OCH}}_{\text{2}}{\text{CH}}_{\text{3}}$. Thus, the solvent ethanol will not interfere in the proposed synthetic step. Hence, the proposed synthetic step is acceptable.

Conclusion

The requirement of the solvent for E2 reactions is aprotic, as aprotic solvents do not solvate the anions (negatively charged ions) as strongly as they solvate cations (positively charged ions).

Interpretation Introduction

(b)

Interpretation:

It is to be determined whether the solvent would interfere with producing the intended target in the proposed synthetic step. For those that would, another solvent that can be used is to be suggested with an explanation.

Concept introduction:

Solvent plays an important role in the proposed synthetic step by not interfering with the reactant molecule or intermediates. For E2 elimination reactions, a strong base is used in the presence of a polar aprotic solvent to yield the most substituted alkene is the major product. The requirement of the solvent for E2 reactions is aprotic, as aprotic solvents do not solvate the anions (negatively charged ions) as strongly as they solvate cations (positively charged ions). If the base used in the reaction and the base produced by the deprotonation of solvent molecules is the same, then the reaction proceeds in the forward direction and the proposed synthetic step is valid and acceptable. If the base used in the reaction is different from the base produced by the deprotonation of solvent molecules, then they would compete and the proposed synthetic route then would not be the valid route.

Answer to Problem 13.33P

The solvent ethanol for the proposed synthetic step is not appropriate. The proposed synthetic step is an example of an E2 reaction, which favors the Zaitsev product (most substituted alkene). The alkoxide ion shown ${{\text{(CH}}_{\text{3}}\text{)}}_{\text{3}}{\text{CO}}^{\text{-}}$ is a strong base and is sufficiently strong to deprotonate the given solvent, which is ethanol. This will generate ethoxide ion, which is a good nucleophile. This would allow a ${\text{S}}_{\text{N}}\text{2}$ reaction that competes with the desired E2 reaction. Instead of ethanol tert-butanol should be used, which will generate the same anion that is a tert-butoxide ion.

Explanation of Solution

The given proposed synthetic step is:

The reactant molecule has a good leaving group, $\text{-Br}$. The reagent used in this step is potassium tert. butoxide which is a source of tert-butoxide ions and is a good base. The product molecule is the alkene, this indicates that the reaction type is an elimination reaction which is E2. An E2 elimination reaction needs a good base and an aprotic solvent. The solvent in the given step is ethanol, which is a polar protic solvent. The alkoxide ion shown ${{\text{(CH}}_{\text{3}}\text{)}}_{\text{3}}{\text{CO}}^{\text{-}}$ is a strong base and is sufficiently strong to deprotonate the given solvent, which is ethanol. This will generate ethoxide ion, which is a good nucleophile. This would allow a ${\text{S}}_{\text{N}}\text{2}$ reaction that competes with the desired E2 reaction. Thus, the solvent ethanol will interfere in the proposed synthetic step. Instead of ethanol tert-butanol should be used, which will generate the same anion that is a tert-butoxide ion or any other aprotic solvent such as DMSO could be used.

Conclusion

The requirement of the solvent for E2 reactions is aprotic, as aprotic solvents do not solvate the anions (negatively charged ions) as strongly as they solvate cations (positively charged ions).

Interpretation Introduction

(c)

Interpretation:

It is to be determined whether the solvent would interfere with producing the intended target in the proposed synthetic step. For those that would, another solvent that can be used is to be suggested with an explanation.

Concept introduction:

Solvent plays an important role in the proposed synthetic step by not interfering with the reactant molecule or intermediates.

For a substitution reaction which follows ${\text{S}}_{\text{N}}\text{2}$ mechanism, a strong nucleophile is required that can attack the electrophilic center in the reactant molecule. The solvent used for a ${\text{S}}_{\text{N}}\text{2}$ reaction has to be aprotic. As aprotic solvents do not solvate the anions (negatively charged ions) as strongly as they solvate cations (positively charged ions). If there are two sufficiently strong nucleophiles are generated in the reaction mechanism, then two different substitution products would be formed instead of the single desired product.

Answer to Problem 13.33P

The solvent ethanol for the proposed synthetic step is not appropriate. The proposed synthetic step is an example of a ${\text{S}}_{\text{N}}\text{2}$ reaction. The alkoxide ion shown is cyclohexanolate ion is a strong base and is sufficiently strong to deprotonate the given solvent, which is ethanol. This will generate ethoxide ion, which is a good nucleophile. This would allow a ${\text{S}}_{\text{N}}\text{2}$ reaction that competes with the desired E2 reaction. Instead of ethanol cyclohexanol should be used, which will generate the same anion that is a tert-butoxide ion or any other aprotic solvent such as DMSO could be used.

Explanation of Solution

The given proposed synthetic step is:

The reactant molecule has a moderate leaving group, $\text{-Cl}$. The reagent used in this step is sodium cyclohexanolate which is a source of cyclohexanolate ions and is a good base. The product molecule is the substitution product. This indicates that it is a ${\text{S}}_{\text{N}}\text{2}$ reaction.

A ${\text{S}}_{\text{N}}\text{2}$ reaction needs a good nucleophile and an aprotic solvent. The solvent in the given step is ethanol, which is a polar protic solvent. The cyclohexanolate ion shown is a strong nucleophile and is sufficiently strong to deprotonate the given solvent, which is ethanol. This will generate ethoxide ion, which is also a good nucleophile. This would allow another ${\text{S}}_{\text{N}}\text{2}$ reaction and a different product than the desired product.

Thus, the solvent ethanol will interfere in the proposed synthetic step. Instead of ethanol cyclohexanol should be used, which will generate the same anion that is cyclohexanolate ion or any other aprotic solvent such as DMSO could be used.

Conclusion

The requirement of the solvent for ${\text{S}}_{\text{N}}\text{2}$ reactions is aprotic, as aprotic solvents do not solvate the anions (negatively charged ions) as strongly as they solvate cations (positively charged ions).

Interpretation Introduction

(d)

Interpretation:

It is to be determined whether the solvent would interfere with producing the intended target in the proposed synthetic step. For those that would, another solvent that can be used is to be suggested with an explanation.

Concept introduction:

Solvent plays an important role in the proposed synthetic step by not interfering with the reactant molecule or intermediates.

For a substitution reaction which follows ${\text{S}}_{\text{N}}\text{2}$ mechanism, a strong nucleophile is required that can attack the electrophilic center in the reactant molecule. The solvent used for a ${\text{S}}_{\text{N}}\text{2}$ reaction has to be aprotic. As aprotic solvents do not solvate the anions (negatively charged ions) as strongly as they solvate cations (positively charged ions). If there are two sufficiently strong nucleophiles are generated in the reaction mechanism, then two different substitution products would be formed instead of the single desired product.

Answer to Problem 13.33P

The solvent for the proposed synthetic step is appropriate. The proposed synthetic step is an example of an E2 reaction, which favors the Zaitsev product (most substituted alkene). If the solvent ethanol is deprotonated, the result is still an ethoxide ion which is the same base that is already shown.

Explanation of Solution

The given proposed synthetic step is:

The reactant molecule has a good leaving group, $\text{-Cl}$. The reagent used in this step is sodium phenoxide which is a source of phenoxide ion and is a good nucleophile as well as a good base. The product molecule is the substitution product. This all indicates that the reaction follows a ${\text{S}}_{\text{N}}\text{2}$ mechanism. The requirement of the solvent for a ${\text{S}}_{\text{N}}\text{2}$ reaction is polar protic. The solvent in the given step is ethanol, which is a polar protic solvent. But, sodium phenoxide is not sufficiently strong to deprotonate the solvent ethanol. Thus, the solvent ethanol will not interfere in the proposed synthetic step. Hence, the proposed synthetic step is acceptable.

Conclusion

The requirement of the solvent for ${\text{S}}_{\text{N}}\text{2}$ reactions is aprotic, as aprotic solvents do not solvate the anions (negatively charged ions) as strongly as they solvate cations (positively charged ions).