Chapter 11 Carboxylic Acid Derivatives

1. Chapter 11Carboxylic Acid Derivatives Chapter 11

2. Acid Derivatives • All can be converted to the carboxylic acid by acidic or basic hydrolysis. • Esters and amides common in nature. Chapter 11

3. ethyl ethanoate ethyl acetate ethanol ethyl alcohol ethanoic acid acetic acid Naming Esters • Esters are named as alkyl carboxylates. • Alkyl from the alcohol, carboxylate from the carboxylic acid precursor. Chapter 11

4. Name These Chapter 11

5. Name These Chapter 11

6. benzyl formate benzyl methanoate Name These isobutyl acetate 2-methylpropyl ethanoate Chapter 11

7. 4-hydroxy-2-methylpentanoic acid lactone -methyl--valerolactone Cyclic Esters • Reaction of -OH and -COOH on same molecule produces a cyclic ester, lactone. • To name, add word lactone to the IUPAC acid name or replace the -ic acid of common name with -olactone. Chapter 11

8. Bond angles around N are close to 120. Amides • Product of the reaction of a carboxylic acid and ammonia or an amine. • Not basic because the lone pair on nitrogen is delocalized by resonance. Chapter 11

9. Classes of Amides • 1 amide has one C-N bond (two N-H). • 2 amide or N-substituted amide has two C-N bonds (one N-H). • 3 amide or N,N-disubstituted amide has three C-N bonds (no N-H). Chapter 11

10. N-ethyl-N,2-dimethylpropanamide N-ethyl-N-methylisobutyramide Naming Amides • For 1 amide, drop -ic or -oic acid from the carboxylic acid name, add -amide. • For 2 and 3 amides, the alkyl groups bonded to nitrogen are named with N- to indicate their position. Chapter 11

11. 4-aminopentanoic acid lactam -valerolactam Cyclic Amides • Reaction of -NH2 and -COOH on same molecule produces a cyclic amide, lactam. • To name, add word lactam to the IUPAC acid name or replace the -ic acid of common name with -olactam. Chapter 21

12. Nitriles • -CN can be hydrolyzed to carboxylic acid, so nitriles are acid derivatives. • Nitrogen is sp hybridized, lone pair tightly held, so not very basic (pKb about 24). Chapter 11

13. Naming Nitriles • For IUPAC names, add -nitrile to the alkane name. • Common names come from the carboxylic acid. Replace -ic acid with -onitrile. 5-bromohexanenitrile -bromocapronitrile Cyclohexanecarbonitrile Chapter 11

14. Acid Halides • More reactive than acids; the halogen withdraws e- density from carbonyl. • Named by replacing -ic acid with -yl halide. 3-bromobutanoyl bromide -bromobutyryl bromide benzoyl chloride Chapter 11

15. Acid Anhydrides • Two molecules of acid combine with the loss of water to form the anhydride. • Anhydrides are more reactive than acids, but less reactive than acid chlorides. • A carboxylate ion is the leaving group in nucleophilic acyl substitution reactions. Chapter 11

16. 1,2-benzenedicarboxylic anhydride phthalic anhydride => Naming Anhydrides • The word acid is replaced with anhydride. • For a mixed anhydride, name both acids. • Diacids may form anhydrides if a 5- or 6-membered ring is the product. ethanoic anhydride acetic anhydride Chapter 11

17. ethyl o-cyanobenzoate Multifunctional Compounds • The functional group with the highest priority determines the parent name. • Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne. Chapter 11

18. Boiling Points Even 3 amides have strong attractions. Chapter 11

19. m.p. 79C Melting Points • Amides have very high melting points. • Melting points increase with increasing number of N-H bonds. m.p. -61C m.p. 28C Chapter 11

20. Solubility • Acid chlorides and anhydrides are too reactive to be used with water or alcohol. • Esters, 3 amides, and nitriles are good polar aprotic solvents. • Solvents commonly used in organic reactions: • Ethyl acetate • Dimethylformamide (DMF) • Acetonitrile Chapter 11

21. Interconversion ofAcid Derivatives • Nucleophile adds to the carbonyl to form a tetrahedral intermediate. • Leaving group leaves and C=O regenerates. Chapter 11

22. Reactivity Reactivity decreases as leaving group becomes more basic. Chapter 11

23. Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. Chapter 11

24. Acid Chloride to Anhydride • Acid or carboxylate ion attacks the C=O. • Tetrahedral intermediate forms. • Chloride ion leaves, C=O is restored, H+ is abstracted. Chapter 11

25. Acid Chloride to Ester • Alcohol attacks the C=O. • Tetrahedral intermediate forms. • Chloride ion leaves, C=O is restored, H+ is abstracted. Chapter 11

26. Acid Chloride to Amide • Ammonia yields a 1 amide • A 1 amine yields a 2 amide • A 2 amine yields a 3 amide Chapter 11

27. Anhydride to Ester • Alcohol attacks one C=O of anhydride. • Tetrahedral intermediate forms. • Carboxylate ion leaves, C=O is restored, H+ is abstracted. => Chapter 11

28. Anhydride to Amide • Ammonia yields a 1 amide • A 1 amine yields a 2 amide • A 2 amine yields a 3 amide Chapter 11

29. Surprise! Ester to Amide • Nucleophile must be NH3 or 1 amine. • Prolonged heating required. Chapter 11

30. Leaving Groups A strong base is not usually a leaving group unless it’s in an exothermic step. Chapter 11

31. Transesterification • One alkoxy group can be replaced by another with acid or base catalyst. • Use large excess of preferred alcohol. Chapter 11

32. TRANSESTERIFICATION OF COCAINE

33. => Hydrolysis of Acid Chlorides andAnhydrides • Hydrolysis occurs quickly, even in moist air with no acid or base catalyst. • Reagents must be protected from moisture. Chapter 11

34. => Acid Hydrolysis of Esters • Reverse of Fischer esterification. • Reaches equilibrium. • Use a large excess of water. Chapter 11

35. Saponification • Base-catalyzed hydrolysis of ester. • “Saponification” means “soap-making.” • Soaps are made by heating NaOH with a fat (triester of glycerol) to produce the sodium salt of a fatty acid - a soap. • One example of a soap is sodium stearate, Na+ -OOC(CH2)16CH3. Chapter 11

36. Hydrolysis of Amides Prolonged heating in 6 M HCl or 40% aqueous NaOH is required. Chapter 11

37. Hydrolysis of Nitriles • Under mild conditions, nitriles hydrolyze to an amide. • Heating with aqueous acid or base will hydrolyze a nitrile to an acid. Chapter 11

38. Reduction to Alcohols Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols. Chapter 11

39. Acid Chloride Synthesis • Use thionyl chloride, SOCl2, or oxalyl chloride, (COCl)2. • Other products are gases. Chapter 11

40. acid anhydride Acid Chloride Reactions (1) acid ester amide Chapter 11

41. Lab Synthesis of Anhydrides • React acid chloride with carboxylic acid or carboxylate ion. • Heat dicarboxylic acids to form cyclic anhydrides. Chapter 11

42. acylbenzene Anhydride Reactions acid ester amide AlCl3 Chapter 11

43. Anhydride vs. Acid Chloride • Acetic anhydride is cheaper, gives a better yield than acetyl chloride. • Use acetic formic anhydride to produce formate esters and formamides. • Use cyclic anhydrides to produce a difunctional molecule. Chapter 11

44. acid acid chloride acid anhydride methyl ester Synthesis of Esters Chapter 11

45. acid acid chloride acid anhydride ester nitrile Synthesis of Amides Chapter 11

46. nitrile Reactions of Amides acid and amine amine 1° amine Chapter 11

47. Polyamides Nylon 6.6 Chapter 11

48. 1° amide alkyl halide diazonium salt aldehyde or ketone cyanohydrin Synthesis of Nitriles Chapter 11

49. Polycarbonates Long-chain esters of carbonic acid Chapter 11

50. Polyurethanes A diol reacts with a diisocyanate. Chapter 11