20.6 Sources of Esters

1. 20.6Sources of Esters

2. O CH3COCH2CH2CH(CH3)2 Esters are very common natural products • also called "isopentyl acetate" and "isoamyl acetate" • contributes to characteristic odor of bananas 3-methylbutyl acetate

3. O CH2OCR' O RCOCH CH2OCR" O Esters of Glycerol • R, R', and R" can be the same or different • called "triacylglycerols," "glyceryl triesters," or "triglycerides" • fats and oils are mixtures of glyceryl triesters

4. O CH2OC(CH2)16CH3 O CH3(CH2)16COCH CH2OC(CH2)16CH3 O Esters of Glycerol Tristearin: found in many animal and vegetable fats

5. O CH2(CH2)6CH3 O H H Cyclic Esters (Lactones) (Z)-5-Tetradecen-4-olide(sex pheromone of female Japanese beetle)

6. Preparation of Esters • Fischer esterification (Sections 15.8 and 19.14) • from acyl chlorides (Sections 15.8 and 20.3) • from carboxylic acid anhydrides (Sections 15.8and 20.5) • Baeyer-Villiger oxidation of ketones (Section 17.16)

7. 20.7Physical Properties of Esters

8. CH3 CH3CHCH2CH3 OH CH3CHCH2CH3 Boiling Points boilingpoint • Esters have higher boiling points than alkanes because they are more polar. • Esters cannot form hydrogen bonds to other ester molecules, so have lower boiling points than alcohols. 28°C O 57°C CH3COCH3 99°C

9. CH3 CH3CHCH2CH3 OH CH3CHCH2CH3 Solubility in Water Solubility(g/100 g) • Esters can form hydrogen bonds to water, so low molecular weight esters have significant solubility in water. • Solubility decreases with increasing number of carbons. ~0 O 33 CH3COCH3 12.5

10. 20.8Reactions of Esters:A Review and a Preview

11. Reactions of Esters • with Grignard reagents (Section 14.10) • reduction with LiAlH4 (Section 15.3) • with ammonia and amines (Sections 20.13) • hydrolysis (Sections 20.9 and 20.10)

12. 20.9Acid-Catalyzed Ester Hydrolysis

13. O O H+ + RCOR' H2O RCOH Acid-Catalyzed Ester Hydrolysis is the reverse of Fischer esterification • maximize conversion to ester by removing water • maximize ester hydrolysis by having large excess of water • equilibrium is closely balanced because carbonyl group ofester and of carboxylic acid are comparably stabilized + R'OH

14. O + H2O CHCOCH2CH3 Cl HCl, heat O + CH3CH2OH CHCOH Cl Example (80-82%)

15. Mechanism of Acid-CatalyzedEster Hydrolysis • Is the reverse of the mechanism for acid-catalyzed esterification. • Like the mechanism of esterification, it involves two stages: • 1) formation of tetrahedral intermediate (3 steps) • 2) dissociation of tetrahedral intermediate (3 steps)

16. O + RCOR' H2O OH OR' RC OH First stage: formation of tetrahedral intermediate • water adds to the carbonyl group of the ester • this stage is analogous to the acid-catalyzed addition of water to a ketone H+

17. O RCOH OH OR' RC OH Second stage: cleavage of tetrahedralintermediate + R'OH H+

18. Mechanism of formationoftetrahedral intermediate

19. H •• O H O •• •• + H RC O R' •• •• Step 1

20. H H O •• + H H O •• •• H O R' Step 1 •• O •• RC O R' •• •• •• + H O RC •• ••

21. •• H O •• RC + O R' •• •• + H O RC O R' •• Step 1 • carbonyl oxygen is protonated because cation produced is stabilized by electron delocalization (resonance) ••

22. •• + H O H RC O •• •• H O R' •• Step 2 ••

23. •• OH H •• + RC O •• H OR' •• •• •• + H O H RC O •• •• H O R' •• Step 2 ••

24. •• OH H •• + H RC O •• O H •• •• OR' •• •• H Step 3

25. •• OH H •• + H RC O •• O H •• •• OR' •• •• H •• OH H •• H RC O •• + •• O H •• OR' •• •• H Step 3

26. Cleavage of tetrahedralintermediate

27. •• OH •• •• RC OH H •• O O H •• •• •• R' + H Step 4

28. •• OH •• •• H RC OH •• + O •• •• O H •• R' H •• OH •• •• RC OH H •• O O H •• •• •• R' + H Step 4

29. •• OH •• •• RC OH •• + O H •• R' Step 5

30. •• OH •• •• RC OH •• + O H •• R' •• OH •• •• O RC H •• R' + •• OH •• Step 5 +

31. •• •• + OH OH •• RC RC + •• •• OH OH •• •• Step 5

32. •• H H O + H •• O •• •• H H O RC •• •• OH •• •• + O H RC •• OH •• Step 6

33. Key Features of Mechanism • Activation of carbonyl group by protonation of carbonyl oxygen • Nucleophilic addition of water to carbonyl groupforms tetrahedral intermediate • Elimination of alcohol from tetrahedral intermediate restores carbonyl group

34. O COCH2CH3 O COCH2CH3 18O Labeling Studies + H2O • Ethyl benzoate, labeled with 18O at the carbonyl oxygen, was subjected to acid-catalyzed hydrolysis. • Ethyl benzoate, recovered before the reaction had gone to completion, had lost its 18O label. • This observation is consistent with a tetrahedral intermediate. H+ + H2O

35. O COCH2CH3 OH OCH2CH3 C OH O COCH2CH3 18O Labeling Studies + H2O H+ H+ + H2O

36. 20.10Ester Hydrolysis in Base:Saponification

37. O O + RCOR' HO– RCO– Ester Hydrolysis in Aqueous Base • is called saponification • is irreversible, because of strong stabilization of carboxylateion • if carboxylic acid is desired product, saponification is followedby a separate acidification step (simply a pH adjustment) + R'OH

38. O O + RCOR' HO– RCO– O RCOH Ester Hydrolysis in Aqueous Base + R'OH H+

39. O CH2OCCH3 CH3 O CH2OH CH3CONa CH3 Example + NaOH water-methanol, heat + (95-97%)

40. O H2C CCOCH3 CH3 1. NaOH, H2O, heat 2. H2SO4 O H2C CCOH CH3 Example + CH3OH (87%)

41. O CH2OC(CH2)xCH3 O CH3(CH2)yCOCH CH2OC(CH2)zCH3 O O O O Soap-Making • Basic hydrolysis of the glyceryl triesters (from fats and oils) gives salts of long-chain carboxylic acids. • These salts are soaps. K2CO3, H2O, heat CH3(CH2)xCOK CH3(CH2)yCOK CH3(CH2)zCOK

42. •• •• O O •• •• – – •• •• •• •• + RCO + R' OH R'OH RCO •• •• •• •• •• •• Which bond is broken when esters arehydrolyzed in base? • One possibility is an SN2 attack by hydroxide on the alkyl group of the ester (alkyl-oxygen cleavage). Carboxylate is the leaving group.

43. •• •• O O •• •• – – •• •• •• •• RC OR' OH OR' RC OH •• •• •• •• •• •• Which bond is broken when esters arehydrolyzed in base? • A second possibility is nucleophilic acyl substitution (acyl-oxygen cleavage). + +

44. O + CH3CH2COCH2CH3 NaOH O + CH3CH2CONa CH3CH2OH 18O Labeling gives the answer • 18O retained in alcohol, not carboxylate; therefore nucleophilic acyl substitution (acyl-oxygen cleavage).

45. H O C6H5 CH3C C O CH3 H O C6H5 CH3COK C HO CH3 Stereochemistry gives the same answer • alcohol has same configuration at stereogenic center as ester; therefore, nucleophilic acyl substitution (acyl-oxygen cleavage) • not SN2 KOH, H2O +

46. •• •• O O •• •• – – •• •• •• •• RC OR' OH OR' RC OH •• •• •• •• •• •• Does it proceed via a tetrahedral intermediate? • Does nucleophilic acyl substitution proceed in a single step, or is a tetrahedral intermediate involved? + +

47. O COCH2CH3 O COCH2CH3 18O Labeling Studies + H2O • Ethyl benzoate, labeled with 18O at the carbonyl oxygen, was subjected to hydrolysis in base. • Ethyl benzoate, recovered before the reaction had gone to completion, had lost its 18O label. • This observation is consistent with a tetrahedral intermediate. HO– + H2O

48. O COCH2CH3 OH OCH2CH3 C OH O COCH2CH3 18O Labeling Studies + H2O HO– HO– + H2O

49. Mechanism of Ester Hydrolysisin Base • Involves two stages: • 1) formation of tetrahedral intermediate2) dissociation of tetrahedral intermediate

50. O + RCOR' H2O OH OR' RC OH First stage: formation of tetrahedral intermediate • water adds to the carbonyl group of the ester • this stage is analogous to the base-catalyzed addition of water to a ketone HO–