Question

When nucleophilic substitution occurs at a carbonyl, the weakest base is usually the best leaving group. What is the order of reactivity in a nucleophilic substitution reaction from most reactive to least reactive for the following compounds? 1\. acid chloride II. ester III. amide A. 1, II, III B. I. III, II C. III, I, II D. III, II, I

Short answer

A. I, II, III

Step-by-step solution

Identify the functional groups

Understand the compounds given: acid chloride, ester, and amide. These are compounds with the following structures: - Acid chloride: RCOCl- Ester: RCOOR'- Amide: RCONH2

Review leaving groups and their stability

Recall that the best leaving group is usually the weakest base. Compare the leaving groups for each compound:- Acid chloride: Cl- (relatively weak base)- Ester: OR'- (stronger base than Cl-, but still relatively weak)- Amide: NH2- (strongest base among the groups)

Determine the reactivity order

Since weaker bases are better leaving groups, the reactivity decreases as the base strength of the leaving group increases. The order from most to least reactive is: 1. Acid chloride (Cl-)2. Ester (OR'-)3. Amide (NH2-)

Match to the given choices

The given order of reactivity from most to least reactive corresponds to Choice A: I, II, III. Therefore, A is the correct answer.

Key concepts

Functional Groups in Organic Chemistry

Understanding functional groups is crucial in organic chemistry. Functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules.
In the exercise, the functional groups we focus on are:

• Acid Chlorides (RCOCl) - contain a carbonyl group (C=O) attached to a chlorine atom.
• Esters (RCOOR') - have a carbonyl group bonded to an alkoxy group (OR').
• Amides (RCONH2) - contain a carbonyl group bonded to an amino group (NH2).

These groups influence the molecule's reactivity, especially in nucleophilic substitution reactions. The reactivity order of these molecules can be explained by examining the leaving groups and their ability to stabilize the negative charge after departure.

Leaving Groups Stability

Leaving group stability is critical in determining the reactivity of compounds in nucleophilic substitution reactions. A leaving group is an atom or group that can depart with a pair of electrons, thus stabilizing the negative charge it carries.
The best leaving groups are usually the weakest bases because they can better stabilize their negative charge. For the compounds in the exercise:

• Acid Chloride (Cl-): Chloride ion (Cl-) is a weak base, making it an excellent leaving group.
• Ester (OR'): Alkoxy group (OR') is a stronger base than chloride but still relatively weak, making it a fair leaving group.
• Amide (NH2-): Amino group (NH2-) is a strong base, making it a poor leaving group.

With this understanding, we can determine that acid chlorides are the most reactive in nucleophilic substitution reactions, followed by esters, and then amides, due to the stability of their leaving groups.

Reactivity Order of Carbonyl Compounds

The reactivity of carbonyl compounds in nucleophilic substitution reactions depends on the stability of their leaving groups.
Since weaker bases make better leaving groups, the order of reactivity from most to least reactive for the given compounds is:

• Acid Chlorides: With Cl- as the leaving group, acid chlorides are the most reactive because Cl- is a weak base and a very stable leaving group.
• Esters: Having OR' as the leaving group, esters are moderately reactive. OR' is a weaker base than NH2- but stronger than Cl-.
• Amides: With NH2- as the leaving group, amides are the least reactive. NH2- is a strong base and a poor leaving group.

Therefore, the reactivity hierarchy in nucleophilic substitution reactions for these carbonyl compounds is: acid chloride > ester > amide. This matches the correct choice in the exercise: I, II, III.