Question

Consider the following molecules:
 
The order of rate of hydrolysis is:

• A. \( r>q>p>s \)
• B. \( q>p>r>s \)
• C. \( p>q>r>s \)
• D. \( p>r>q>s \)

Hint:

For nucleophilic substitution reactions, the stability of the leaving group is key. Chlorine, being a good leaving group, affects the rate of hydrolysis.

Answer 1

The Correct Option is C

The objective is to rank the rate of hydrolysis for four carboxylic acid derivatives: an acyl chloride (p), an acid anhydride (q), an ester (r), and an amide (s).

Concept Used:

Hydrolysis of carboxylic acid derivatives proceeds via nucleophilic acyl substitution. The mechanism involves nucleophilic attack by water on the carbonyl carbon, followed by the expulsion of a leaving group.

The reaction rate is governed by two principal factors:

1. Carbonyl Carbon Electrophilicity: A more positively charged carbonyl carbon (higher \(\delta+\)) is more susceptible to nucleophilic attack, thus increasing the reaction rate. Electron-withdrawing substituents enhance electrophilicity, while electron-donating substituents diminish it.
2. Leaving Group Stability: The rate of hydrolysis is directly proportional to the stability of the departing group. A good leaving group is the conjugate base of a strong acid, meaning it is a weak base. This factor is predominant.

Step-by-Step Solution:

Step 1: Identify the leaving group for each molecule during hydrolysis.

In hydrolysis, the bond between the carbonyl carbon and the leaving group (L) cleaves.

• For propanoyl chloride (p), the leaving group is chloride ion, Cl\(^-\).
• For the acid anhydride (q), the leaving group is the carboxylate ion, CH\( _3 \)COO\( ^- \) (ethanoate).
• For ethyl propanoate (r), the leaving group is the ethoxide ion, CH\( _3 \)CH\( _2 \)O\( ^- \).
• For propanamide (s), the leaving group is the amide ion, NH\( _2 ^- \).

Step 2: Compare leaving group stability based on their basicity.

Leaving group stability is inversely correlated with basicity; weaker bases are more stable leaving groups. Basicity is inferred from the acidity of their conjugate acids (HCl, CH\( _3 \)COOH, CH\( _3 \)CH\( _2 \)OH, NH\( _3 \)).

The acidity order of the conjugate acids is:

\[ \text{HCl} > \text{CH}_3\text{COOH} > \text{CH}_3\text{CH}_2\text{OH} > \text{NH}_3 \]

(Strongest acid) \(\quad\) (Weakest acid)

Conversely, the basicity order of the conjugate bases (leaving groups) is:

\[ \text{NH}_2^- > \text{CH}_3\text{CH}_2\text{O}^- > \text{CH}_3\text{COO}^- > \text{Cl}^- \]

(Strongest base / Poorest leaving group) \(\quad\) (Weakest base / Best leaving group)

Step 3: Relate leaving group ability to the rate of hydrolysis.

The ease with which a leaving group departs directly influences the reaction rate. Therefore, the hydrolysis reactivity order mirrors the leaving group ability order (which is the inverse of their basicity).

Order of leaving group ability:

\[ \text{Cl}^- > \text{CH}_3\text{COO}^- > \text{CH}_3\text{CH}_2\text{O}^- > \text{NH}_2^- \]

This corresponds to the molecules:

\[ \text{(p) > (q) > (r) > (s)} \]

Step 4: Confirm the order by considering carbonyl carbon electrophilicity.

Substituents attached to the carbonyl carbon affect its electrophilicity through inductive (-I) and resonance (+M) effects.

• (p) Acyl Chloride (-Cl): Exhibits a strong -I effect and a weak +M effect (due to poor 2p-3p orbital overlap), resulting in high carbonyl carbon electrophilicity.
• (q) Anhydride (-OCOR): The electron-withdrawing nature of this group renders the carbonyl carbon highly electrophilic.
• (r) Ester (-OR): The oxygen lone pair provides a strong +M effect, donating electron density and reducing carbonyl electrophilicity more than its -I effect increases it.
• (s) Amide (-NH\( _2 \)): Nitrogen's lone pair is more available for donation (+M effect) than oxygen's due to lower electronegativity. This very strong +M effect significantly reduces carbonyl electrophilicity, making it the least reactive.

This analysis reinforces the determined order of reactivity.

Consequently, the order of hydrolysis rates is (p) > (q) > (r) > (s).