1. Dr. Wolf's CHM 201 & 202 20-1 Ester Hydrolysis in Base: Saponification

2. 20-2 is called saponification is irreversible, because of strong stabilization of carboxylate ion if carboxylic acid is desired product, saponification is followed by a separate acidification step (simply a pH adjustment) Ester Hydrolysis in Aqueous Base RCO – O+ R'OH RCOR' O+ HO –

3. 20-3 Soap-Making R 2 COCH R 2 COCH CH 2 OCR 1 O CH 2 OCR 3 O O Basic hydrolysis of the glyceryl triesters (from fats and oils) gives salts of long-chain carboxylic acids. These salts are soaps. NaOH, H 2 O, heat R 1 CONa R 1 CONaO R 2 CONa R 2 CONaO R 3 CONa R 3 CONaO

4. 20-4 Which bond is broken when esters are hydrolyzed in base? + –OH RC O OR'OR'OR'OR' + OR' – nucleophilic acyl substitution. RC O OH

5. Dr. Wolf's CHM 201 & 202 20-5 Stereochemistry gives the same answer alcohol has same configuration at chirality center as ester; therefore, nucleophilic acyl substitution CH 3 CONa O+ CH 3 C O C OH C6H5C6H5C6H5C6H5 CH 3 C HOHOHOHOH C6H5C6H5C6H5C6H5 NaOH, H 2 O

6. 20-6 Involves two stages: 1)formation of tetrahedral intermediate 2)dissociation of tetrahedral intermediate Mechanism of Ester Hydrolysis in Base

7. 20-7 First stage: formation of tetrahedral intermediate RCOHOH OR' + H2OH2OH2OH2O RCOR' O water adds to the carbonyl group of the ester this stage is analogous to the base-catalyzed addition of water to a ketone HO –

8. Mechanism of formation of tetrahedral intermediate

9. Step 1 RC O OR' RC O OR' O H – O H –

10. Step 2 RC O OR' O H – HO H RC O OR' O H H – O H

11. Dr. Wolf's CHM 201 & 202 Dissociation of tetrahedral intermediate

12. Step 3 RC O OR' O H H – O H HO H OR' – RC O O H

13. Step 4 OR' – RC O O H HO – RC O O – H OR' H2OH2OH2OH2O

14. Nucleophilic addition of hydroxide ion to carbonyl group in first step Tetrahedral intermediate formed in first stage Hydroxide-induced dissociation of tetrahedral intermediate in second stage Key Features of Mechanism