5. Carbonyls

Question 1

What are tetrahedral intermediates in nucleophilic substitution at carbonyls?

Answer 1

Tetrahedral intermediates are formed when good nucleophiles rapidly displace good leaving groups.

The overall energy barrier is influenced by the leaving group quality.

Question 2

What is the significance of the leaving group in nucleophilic substitution reactions?

Answer 2

The leaving group determines the height of the second barrier beyond the tetrahedral intermediate.

Poor leaving groups contribute to a higher energy barrier.

Question 3

What is the preferred angle of attack for nucleophiles in tetrahedral intermediates?

Answer 3

The preferred angle of attack is approximately 110 degrees.

This angle is related to the repulsion between the incoming nucleophile and the adjacent orbital.

Question 4

What are the two main mechanisms for ester hydrolysis?

Answer 4

• B2 (Base-induced, acyl-oxygen cleavage, bimolecular)
• A2 (Acid-catalyzed, acyl-oxygen cleavage, bimolecular)

B2 is not a base-catalyzed reaction despite its name.

Question 5

What does isotopic labeling in ester hydrolysis help to track?

Answer 5

Isotopic labeling helps to track the oxygen atoms in the tetrahedral intermediate.

This can show which bonds are broken during the reaction.

Question 6

What happens when the OR’ group is labeled during ester hydrolysis?

Answer 6

Labeling the OR’ group produces labeled alcohol, HOR’, indicating that the O-R’ bond has been broken.

This confirms the role of the leaving group in the reaction.

Question 7

What is the result of labeling the hydroxide during the hydrolysis reaction?

Answer 7

Labeling the hydroxide produces labeled carboxylate, confirming that the acyl oxygen bond has been broken.

This indicates the pathway of the reaction.

Question 8

What does the kinetic expression for ester hydrolysis indicate about the reaction mechanism?

Answer 8

The kinetic expression suggests a simple bimolecular displacement with a single tetrahedral intermediate.

This implies that the reaction does not provide evidence for multiple intermediates.

Question 9

True or False: Hindered acids react more quickly in nucleophilic substitution reactions.

Answer 9

False. Hindered acids react more slowly.

This results in a bimolecular reaction likelihood.

Question 10

Fill in the blank: The rate of ester hydrolysis is proportional to ______.

Answer 10

[K] * [ester] * [HO-].

Question 11

What is the relationship between the quality of the leaving group and the rate of reaction in ester hydrolysis?

Answer 11

RCox with a good leaving group (e.g., X - OPh) has a higher rate constant than RCOX with a bad leaving group (e.g., amide).

This underscores the importance of leaving group ability in reaction kinetics.

Question 12

What is Au2 in the context of acid-catalysed ester hydrolysis?

Answer 12

Acid-catalysed, acyl-oxygen cleavage, bimolecular

This mechanism describes a specific type of reaction involving esters in the presence of an acid catalyst.

Question 13

Why is water considered a poor nucleophile in ester hydrolysis?

Answer 13

Water is a poor nucleophile, so it will only participate under specific conditions.

This limits the rate of reaction, as nucleophiles are essential for the reaction to proceed.

Question 14

What characterizes the steps in acid-catalysed ester hydrolysis?

Answer 14

All steps are reversible and the reaction continues until it reaches an equilibrium.

This implies that the concentration of reactants and products will stabilize at a certain point.

Question 15

What is the significance of kinetic measurements in acid-catalysed ester hydrolysis?

Answer 15

Only rates in the early stages of the reaction are significant for kinetic measurements.

This means that later stages are influenced by previous steps and are not useful for determining reaction rates.

Question 16

What does isotopic labeling reveal about the mechanism of ester hydrolysis?

Answer 16

Isotopic labeling shows that the reaction involves acyl-oxygen cleavage through tetrahedral intermediates.

This method helps track the movement of atoms during the reaction.

Question 17

What is the role of tetrahedral intermediates in acid-catalysed ester hydrolysis?

Answer 17

Tetrahedral intermediates are formed during the reaction, but there is also a third, neutral intermediate.

This third intermediate has a different energy profile compared to the other two.

Question 18

How do hindered esters react compared to less hindered ones?

Answer 18

Hindered esters react more slowly due to steric hindrance.

This affects the accessibility of the reactive site for nucleophiles.

Question 19

What is the rate equation for the reaction involving tetrahedral intermediates?

Answer 19

Rate = k[H2O][ester].

This indicates that the reaction rate depends on the concentration of both water and the ester.

Question 20

What are the two less common mechanisms for acid hydrolysis of esters?

Answer 20

1. Au1 mechanism
2. An alternative mechanism that does not go via tetrahedral intermediates.

These mechanisms can lead to stable cations in strong acid.

Question 21

What is required for the Au1 mechanism to occur?

Answer 21

Protonation on the alcohol oxygen is required to facilitate the reaction.

This is crucial for the formation of a stable intermediate.

Question 22

What is the rate equation for the Au1 mechanism?

Answer 22

Rate = k[ester][H2O].

This suggests that the reaction behaves as pseudo-first order due to excess acid.

Question 23

How do ortho-methyl groups affect the hydrolysis of esters?

Answer 23

Ortho-methyl groups force the ester group out of the plane of the benzene ring, shielding the carbon from attack.

This steric hindrance can significantly affect the reaction rate.

Question 24

What is the effect of resonance on acylium ions in ester hydrolysis?

Answer 24

Acylium ions are particularly stable due to resonance, influencing the mechanism of hydrolysis.

This stability can direct the reaction towards specific pathways.

Question 25

What is the reaction mechanism described from the alcohol’s perspective?

Answer 25

5,1 reaction

In this mechanism, the protonated ester is a key intermediate.

Question 26

What common types of esters hydrolyse by the mechanism described?

Answer 26

• Triphenylmethyl (trityl) ester
• tert-butyl ester

These esters are known for their hydrolysis under specific conditions.

Question 27

What does isotopic labelling indicate in the hydrolysis of an OR labelled ester?

Answer 27

The @-R bond must have broken

This is inferred because hydrolysis yields HO-R’ from the labelled ester.

Question 28

How does steric hindrance affect the structure of the esters discussed?

Answer 28

Not sensitive to steric hindrance

The mechanism remains effective regardless of steric factors.

Question 29

What is the rate expression for the kinetics of the reaction?

Answer 29

Rate = k_on[ester][H2O]

This indicates a first-order reaction with respect to both ester and water.

Question 30

What is the mechanism of hydrolysis when terf-butyl ester is present?

Answer 30

Protonated to a small extent; slow step is alkyl-oxygen cleavage

Acid catalysis is involved in this process.

Question 31

What is unusual about the hydrolysis of substituted ethyl benzoates in concentrated sulfuric acid?

Answer 31

The concentration of nucleophiles is completely protonated

This leads to the generation of an unstable ethyl cation.

Question 32

In the reaction where acylium ion pathway becomes lower in energy, which substituent is changed?

Answer 32

OMe

This change affects the reaction mechanism and its energy profile.

Question 33

What are the characteristics of the B2 mechanism summary?

Answer 33

• Stoichiometric
• Requires stable acylium ion
• Detects alkyl-O cleavage

This mechanism is identified by specific labelling techniques.

Question 34

What does the p-ve probe in the B2 mechanism detect?

Answer 34

Tet. intermediate(s)

This indicates the presence of stable intermediates in the reaction.

Question 35

What is required for the Ac. 1 mechanism to function?

Answer 35

Stable acylium ion

Pre-protonation is crucial for this mechanism.

Question 36

What does labelling show in the Ac. 1 mechanism?

Answer 36

Acylo-O cleavage

This indicates the breakdown of the acyl-oxygen bond.

Question 37

What is needed for the AN1 mechanism to be effective?

Answer 37

Stable alkyl cation

Pre-protonation in strong acid conditions facilitates this mechanism.

Question 38

What does labelling in the AN1 mechanism detect?

Answer 38

Alkyl-O cleavage

This shows the breakdown of the alkyl-oxygen bond.