Chapter 21 Carboxylic Acid Derivatives

1. Chapter 21Carboxylic Acid Derivatives

2. Chapter 21 2

3. Chapter 21 3 Naming Esters Esters are named as alkyl carboxylates. Alkyl from the alcohol, carboxylate from the carboxylic acid precursor.

4. Chapter 21 4 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.

5. Chapter 21 5 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.

6. Chapter 21 6 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). =>

7. Chapter 21 7 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.

8. Chapter 21 8 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.

9. Chapter 21 9 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).

10. Chapter 21 10 Naming Nitriles For IUPAC names, add -nitrile to the alkane name. Common names come from the carboxylic acid. Replace -ic acid with -onitrile.

11. Chapter 21 11 Acid Halides More reactive than acids; the halogen withdraws e- density from carbonyl. Named by replacing -ic acid with -yl halide.

12. Chapter 21 12 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.

13. Chapter 21 13 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.

14. Chapter 21 14 Multifunctional Compounds The functional group with the highest priority determines the parent name. Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne.

15. Chapter 21 15 Boiling Points

16. Chapter 21 16 Melting Points Amides have very high melting points. Melting points increase with increasing number of N-H bonds.

17. Chapter 21 17 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  =>

18. Chapter 21 18 IR Spectroscopy

19. Chapter 21 19 1H NMR Spectroscopy

20. Chapter 21 20 13C NMR Spectroscopy

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

22. Chapter 21 22 Reactivity Reactivity decreases as leaving group becomes more basic.

23. Chapter 21 23 Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives.

24. Chapter 21 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. =>

25. Chapter 21 25 Acid Chloride to Ester Alcohol attacks the C=O. Tetrahedral intermediate forms. Chloride ion leaves, C=O is restored, H+ is abstracted. =>

26. Chapter 21 26 Acid Chloride to Amide Ammonia yields a 1? amide A 1? amine yields a 2? amide A 2? amine yields a 3? amide

27. Chapter 21 27 Anhydride to Ester Alcohol attacks one C=O of anhydride. Tetrahedral intermediate forms. Carboxylate ion leaves, C=O is restored, H+ is abstracted. =>

28. Chapter 21 28 Anhydride to Amide Ammonia yields a 1? amide A 1? amine yields a 2? amide A 2? amine yields a 3? amide

29. Chapter 21 29 Ester to Amide Nucleophile must be NH3 or 1? amine. Prolonged heating required.

30. Chapter 21 30 Leaving Groups A strong base is not usually a leaving group unless it’s in an exothermic step.

31. Chapter 21 31 Transesterification One alkoxy group can be replaced by another with acid or base catalyst. Use large excess of preferred alcohol.

32. Chapter 21 32 Hydrolysis of Acid Chlorides and Anhydrides Hydrolysis occurs quickly, even in moist air with no acid or base catalyst. Reagents must be protected from moisture.

33. Chapter 21 33 Acid Hydrolysis of Esters Reverse of Fischer esterification. Reaches equilibrium. Use a large excess of water.

34. Chapter 21 34 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. =>

35. Chapter 21 35 Hydrolysis of Amides Prolonged heating in 6 M HCl or 40% aqueous NaOH is required.

36. Chapter 21 36 Hydrolysis of Nitriles Under mild conditions, nitriles hydrolyze to an amide. Heating with aqueous acid or base will hydrolyze a nitrile to an acid.

37. Chapter 21 37 Reduction to Alcohols Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols.

38. Chapter 21 38 Reduction to Aldehydes Acid chlorides will react with a weaker reducing agent to yield an aldehyde.

39. Chapter 21 39 Reduction to Amines Lithium aluminum hydride reduces amides and nitriles to amines. Nitriles and 1? amides reduce to 1? amines. A 2? amide reduces to a 2? amine. A 3? amide reduces to a 3? amine.

40. Chapter 21 40 Organometallic Reagents Grignard reagents and organolithium reagents add twice to acid chlorides and esters to give alcohols after protonation.

41. Chapter 21 41 Grignard Reagentsand Nitriles A Grignard reagent or organolithium reagent attacks the cyano group to yield an imine which is hydrolyzed to a ketone.

42. Chapter 21 42 Acid Chloride Synthesis Use thionyl chloride, SOCl2, or oxalyl chloride, (COCl)2. Other products are gases.

43. Chapter 21 43 Acid Chloride Reactions (1)

44. Chapter 21 44 Acid Chloride Reactions (2)

45. Chapter 21 45 Industrial Synthesis of Acetic Anhydride Four billion pounds/year produced. Use high heat (750°C) and triethyl phosphate catalyst to produce ketene.

46. Chapter 21 46 Lab Synthesisof Anhydrides React acid chloride with carboxylic acid or carboxylate ion.

47. Chapter 21 47 Anhydride Reactions

48. Chapter 21 48 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.

49. Chapter 21 49 Synthesis of Esters

50. Chapter 21 50 Reactions of Esters

51. Chapter 21 51 Lactones Formation favored for five- and six-membered rings.

52. Chapter 21 52 Synthesis of Amides

53. Chapter 21 53 Reactions of Amides

54. Chapter 21 54 Lactam Formation Five- and six-membered rings can be formed by heating ?- and ?-amino acids.

55. Chapter 21 55 ?-Lactams Highly reactive, 4-membered ring. Found in antibiotics isolated from fungi.

56. Chapter 21 56 Synthesis of Nitriles

57. Chapter 21 57 Reactions of Nitriles

58. Chapter 21 58 Thioesters More reactive than esters because: -S-R is a better leaving group than -O-R Resonance overlap is not as effective.

59. Chapter 21 59 Carbonic Acid Esters CO2 in water contains some H2CO3. Diesters are stable. Synthesized from phosgene.

60. Chapter 21 60 Urea and Urethanes Urea is the diamide of carbonic acid. Urethanes are esters of a monoamide of carbonic acid.

61. Chapter 21 61 Polymers Polycarbonates are long-chain esters of carbonic acid. Polyurethanes are formed when a diol reacts with a diisocyanate.

62. Chapter 21 62 End of Chapter 21