CHAPTER TWENTY Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution First stage: Formation of the tetrahedral intermediate by nucleophilic addition of Acyl chloride Tetrahedral intermediate Second stage: Dissociation of the tetrahedral intermediate by dehydrohalogenation R Tetrahedral Water Carboxylic FIGURE 20. 3 Hydrolysis of acyl chloride proceeds by way of a tetrahedral intermediate. For- mation of the tetrahedral intermediate is rate-determini The mechanisms of all the reactions cited in Table 20.2 are similar to the mecha- nism of hydrolysis of an acyl chloride outlined in Figure 20.3. They differ with respect to the nucleophile that attacks the carbonyl group In the first stage of the mechanism, water undergoes nucleophilic addition to the carbonyl group to form a tetrahedral intermediate. This stage of the process is analogous to the hydration of aldehydes and ketones discussed in Section 17.6. The tetrahedral intermediate has three potential leaving groups on carbon: two hydroxyl groups and a chlorine. In the second stage of the reaction, the tetrahedral inter mediate dissociates, Loss of chloride from the tetrahedral intermediate is faster than loss of hydroxide; chloride is less basic than hydroxide and is a better leaving group. The tetrahedral intermediate dissociates because this dissociation restores the resonance- tabilized carbonyl group PROBLEM 20.4 Write the structure of the tetrahedral intermediate formed each of the reactions given in Problem 20. 3. Using curved arrows, show how each tetrahedral intermediate dissociates to the appropriate products SAMPLE SOLUTION (a)The tetrahedral intermediate arises by nucleophilic addi- tion of acetic acid to benzoyl chloride C6HsCCI CH3COH C6HsCOCCH3 Benzoyl Acetic acid Tetrahedral intermediate Loss of a proton and of chloride ion from the tetrahedral intermediate yields the mixed anhydride Back Forward Main MenuToc Study Guide ToC Student o MHHE WebsiteThe mechanisms of all the reactions cited in Table 20.2 are similar to the mecha￾nism of hydrolysis of an acyl chloride outlined in Figure 20.3. They differ with respect to the nucleophile that attacks the carbonyl group. In the first stage of the mechanism, water undergoes nucleophilic addition to the carbonyl group to form a tetrahedral intermediate. This stage of the process is analogous to the hydration of aldehydes and ketones discussed in Section 17.6. The tetrahedral intermediate has three potential leaving groups on carbon: two hydroxyl groups and a chlorine. In the second stage of the reaction, the tetrahedral inter￾mediate dissociates. Loss of chloride from the tetrahedral intermediate is faster than loss of hydroxide; chloride is less basic than hydroxide and is a better leaving group. The tetrahedral intermediate dissociates because this dissociation restores the resonance￾stabilized carbonyl group. PROBLEM 20.4 Write the structure of the tetrahedral intermediate formed in each of the reactions given in Problem 20.3. Using curved arrows, show how each tetrahedral intermediate dissociates to the appropriate products. SAMPLE SOLUTION (a) The tetrahedral intermediate arises by nucleophilic addi￾tion of acetic acid to benzoyl chloride. Loss of a proton and of chloride ion from the tetrahedral intermediate yields the mixed anhydride. C6H5CCl O Benzoyl chloride C6H5COCCH3 HO Cl O Tetrahedral intermediate CH3COH O Acetic acid 782 CHAPTER TWENTY Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution O H H Water C R C R O slow O  O H H fast H O C R O H Acyl chloride Tetrahedral intermediate First stage: Formation of the tetrahedral intermediate by nucleophilic addition of water to the carbonyl group Second stage: Dissociation of the tetrahedral intermediate by dehydrohalogenation H O C R O Cl Tetrahedral intermediate H O H H Water fast C R O H O H H Carboxylic acid Hydronium ion O H Cl Chloride ion  Cl Cl Cl FIGURE 20.3 Hydrolysis of acyl chloride proceeds by way of a tetrahedral intermediate. For￾mation of the tetrahedral intermediate is rate-determining. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website