1. CHE 242 Unit VIII The Structure, Properties, Reactions and Mechanisms of Carboxylic Acids and Their Derivatives CHAPTER TWENTY-ONE Terrence P. Sherlock Burlington County College 2004

2. Chapter 212 Acid Derivatives All can be converted to the carboxylic acid by acidic or basic hydrolysis. Esters and amides common in nature. =>

3. Chapter 213 Naming Esters Esters are named as alkyl carboxylates. Alkyl from the alcohol, carboxylate from the carboxylic acid precursor. isobutyl acetate 2-methylpropyl ethanoate benzyl formate benzyl methanoate =>

4. Chapter 214 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. 4-hydroxy-2-methylpentanoic acid lactone  -methyl-  -valerolactone =>

5. Chapter 215 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. Bond angles around N are close to 120 . =>

6. Chapter 216 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 217 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. N-ethyl-N,2-dimethylpropanamide N-ethyl-N-methylisobutyramide =>

8. Chapter 218 Cyclic Amides Reaction of -NH 2 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. 4-aminopentanoic acid lactam  -valerolactam =>

9. Chapter 219 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. (pK b about 24). =>

10. Chapter 2110 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 =>

11. Chapter 2111 Acid Halides More reactive than acids; the halogen withdraws e - density from carbonyl. Named by replacing -ic acid with -yl halide. benzoyl chloride 3-bromobutanoyl bromide  -bromobutyryl bromide =>

12. Chapter 2112 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 2113 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 1,2-benzenedicarboxylic anhydride phthalic anhydride =>

14. Chapter 2114 Multifunctional Compounds The functional group with the highest priority determines the parent name. Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne. ethyl o-cyanobenzoate =>

15. Chapter 2115 Melting Points Amides have very high melting points. Melting points increase with increasing number of N-H bonds. m.p. -61  Cm.p. 28  Cm.p. 79  C =>

16. Chapter 2116 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 =>

17. Chapter 2117 IR Spectroscopy =>

18. Chapter 2118 1 H NMR Spectroscopy =>

19. Chapter 2119 Interconversion of Acid Derivatives Nucleophile adds to the carbonyl to form a tetrahedral intermediate. Leaving group leaves and C=O regenerates. =>

20. Chapter 2120 Reactivity Reactivity decreases as leaving group becomes more basic. =>

21. Chapter 2121 Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. =>

22. Chapter 2122 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. =>

23. Chapter 2123 Acid Hydrolysis of Esters Reverse of Fischer esterification. Reaches equilibrium. Use a large excess of water. =>

24. Chapter 2124 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(CH 2 ) 16 CH 3. =>

25. Chapter 2125 Hydrolysis of Amides Prolonged heating in 6 M HCl or 40% aqueous NaOH is required. =>

26. Chapter 2126 Hydrolysis of Nitriles Under mild conditions, nitriles hydrolyze to an amide. Heating with aqueous acid or base will hydrolyze a nitrile to an acid. =>

27. Chapter 2127 Reduction to Alcohols Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols. =>

28. Chapter 2128 Reduction to Aldehydes Acid chlorides will react with a weaker reducing agent to yield an aldehyde. =>

29. Chapter 2129 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. =>

30. Chapter 2130 Organometallic Reagents Grignard reagents and organolithium reagents add twice to acid chlorides and esters to give alcohols after protonation. =>

31. Chapter 2131 Grignard Reagents and Nitriles A Grignard reagent or organolithium reagent attacks the cyano group to yield an imine which is hydrolyzed to a ketone. =>

32. Chapter 2132 Acid Chloride Synthesis Use thionyl chloride, SOCl 2, or oxalyl chloride, (COCl) 2. Other products are gases. =>

33. Chapter 2133 Acid Chloride Reactions (1) acid ester amide acid anhydride =>

34. Chapter 2134 Acid Chloride Reactions (2) 3° alcohol ketone 1° alcohol aldehyde acylbenzene =>

35. Chapter 2135 Anhydride Reactions acid ester amide => acylbenzene

36. Chapter 2136 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. =>

37. Chapter 2137 Synthesis of Esters acid acid chloride acid anhydride methyl ester =>

38. Chapter 2138 Reactions of Esters acid ester amide 1° alcohol 3° alcohol =>

39. Chapter 2139 Lactones Formation favored for five- and six- membered rings. For larger rings, remove water to shift equilibrium toward products =>

40. Chapter 2140 Synthesis of Amides acid acid anhydrideesternitrile => acid chloride

41. Chapter 2141 Reactions of Amides acid and amine amine 1° amine => nitrile

42. Chapter 2142 Lactam Formation Five- and six-membered rings can be formed by heating  - and  -amino acids. Smaller or larger rings do not form readily. =>

43. Chapter 2143  -Lactams Highly reactive, 4-membered ring. Found in antibiotics isolated from fungi. Amide  ester !! =>

44. Chapter 2144 Synthesis of Nitriles 1° amide alkyl halide diazonium salt aldehyde or ketone cyanohydrin =>

45. Chapter 2145 Reactions of Nitriles ketone => amide acid 1° amine

46. Chapter 2146 Thioesters More reactive than esters because:  - S-R is a better leaving group than - O-R  Resonance overlap is not as effective. =>

47. Chapter 2147 Carbonic Acid Esters CO 2 in water contains some H 2 CO 3. Diesters are stable. Synthesized from phosgene. =>

48. Chapter 2148 Urea and Urethanes Urea is the diamide of carbonic acid. Urethanes are esters of a monoamide of carbonic acid. =>

49. Chapter 2149 Polymers Polycarbonates are long-chain esters of carbonic acid. Polyurethanes are formed when a diol reacts with a diisocyanate. =>

50. Chapter 2150 POWER POINT IMAGES FROM “ORGANIC CHEMISTRY, 5 TH EDITION” L.G. WADE ALL MATERIALS USED WITH PERMISSION OF AUTHOR PRESENTATION ADAPTED FOR BURLINGTON COUNTY COLLEGE ORGANIC CHEMISTRY COURSE BY: ANNALICIA POEHLER STEFANIE LAYMAN CALY MARTIN