Introduction to Organic Chemistry 2 ed William H. Brown

1. Introduction to Organic Chemistry2 edWilliam H. Brown

2. Carboxyl Derivatives Chapter 13

3. Carboxyl Derivatives • In this chapter, we study four classes of organic compounds. • under the structural formula of each is a drawing to help you see its relationship to the carboxyl group.

4. Structure: Acid Chlorides • The functional group of an acid halide is an acyl group bonded to a halogen • to name, change the suffix -ic acid to -yl halide

5. Acid Anhydrides • The functional group of an acid anhydride is two acyl groups bonded to an oxygen atom • the anhydride may be symmetrical (two identical acyl groups) or mixed (two different acyl groups) • to name, replaceacidof the parent acid by anhydride

6. Acid Anhydrides • Cyclic anhydrides are named from the dicarboxylic acids from which they are derived

7. Acid Anhydrides • A phosphoric acid anhydride contains two phosphoryl groups bonded to an oxygen atom

8. Esters • The functional group of an ester is an acyl group bonded to -OR or -OAr • name the alkyl or aryl group bonded to oxygen; follow by the name of the acid but with the suffix -ic acid changed to -ate

9. Lactones • Cyclic esters are called lactones • Name the parent carboxylic acid, drop the suffix -ic acid, and add -olactone

10. Phosphoric Esters • Phosphoric acid has three -OH groups and forms mono-, di-, and triesters • name the alkyl or aryl group bonded to oxygen followed by the word phosphate

11. Phosphoric Esters • to name more complex phosphoric esters, name the organic molecule followed by the name phosphate

12. Amides • The functional group of an amide is an acyl group bonded to a nitrogen atom • to name, drop -oic acid from the name of the parent acid and add -amide • if the amide nitrogen is bonded to an alkyl or aryl group, name the group and show its location on nitrogen by N-

13. Amides • Cyclic amides are called lactams • name the parent carboxylic acid, drop the suffix -ic acid, and add -lactam

14. Amides • The penicillins are a family of b-lactam antibiotics

15. Penicillin G

16. Amides • The cephalosporins are also b-lactam antibiotics

17. Cefetamet

18. Characteristic Reactions • Nucleophilic acyl substitution: an addition-elimination sequence resulting in substitution of one nucleophile for another

19. Characteristic Reactions • The leaving group as an anion, Y-, to illustrate an important point: the weaker the base, the better the leaving group

20. Characteristic Reactions • halide ion is the weakest base and the best leaving group; acid halides are the most reactive toward nucleophilic acyl substitution • amide ion is the strongest base and the poorest leaving group; amides are the least reactive toward nucleophilic acyl substitution

21. Rexn with H2O - RCOCl • Low-molecular-weight acid chlorides react rapidly with water • Higher-molecular weight acid chlorides are less soluble in water and react less readily

22. Rexn with H2O - Esters • Low-molecular-weight acid anhydrides react readily with water to give two molecules of carboxylic acid • Higher-molecular-weight acid anhydrides also react with water, but less readily

23. Rexn with H2O - Esters • Esters are hydrolyzed only slowly, even in boiling water • hydrolysis becomes more rapid if they are heated with either aqueous acid or base • Hydrolysis in aqueous acid is the reverse of Fischer esterification • the acid catalyst protonates the carbonyl oxygen and increases its electrophilic character toward attack by water to form a tetrahedral carbonyl addition intermediate • collapse of this intermediate gives the carboxylic acid and alcohol

24. Rexn with H2O - Esters • Acid-catalyzed ester hydrolysis

25. Rexn with H2O - Esters • Hydrolysis of an esters is aqueous base is often called saponification • each mol of ester hydrolyzed requires 1 mol of base; for this reason, ester hydrolysis in aqueous base is said to be base-promoted • hydrolysis of an ester in aqueous base involves formation of a tetrahedral carbonyl addition intermediate followed by its collapse and proton transfer

26. Rexn with H2O - Esters • base-promoted ester hydrolysis

27. Rexn with H2O - Amides • hydrolysis of an amide in aqueous acid requires 1 mol of acid per mol of amide

28. Rexn with H2O - Amides • hydrolysis of an amide in aqueous base requires 1 mol of base per mol of amide

29. Rexn with Alcohols • Acid halides react with alcohols to give esters • because acid halides are so reactive toward even weak nucleophiles such as alcohols, no catalyst is necessary

30. Rexn with Alcohols • Acid anhydrides react with alcohols to give one mol of ester and one of carboxylic acid

31. Rexn with Alcohols • Synthesis of aspirin synthesized

32. Rexn with Ammonia, etc. • Acid halides react with ammonia, and 1° and 2° amines to form amides • 2 moles of the amine are required per mole of acid chloride

33. Rexn with Ammonia, etc. • Acid anhydrides react with ammonia, and 1° and 2° amines to form amides. • 2 moles of ammonia or amine are required per mole of anhydride

34. Rexn with Ammonia, etc. • Esters react with ammonia, and 1° and 2° amines to form amides • esters are less reactive than either acid halides or acid anhydrides • Amides do not react with ammonia, or 1° or 2° amines

35. Interconversion • Relative reactivities of carboxyl derivatives

36. Esters with RMgX • A formic ester with 2 moles of RMgX followed by hydrolysis gives a 2° alcohol

37. Esters with RMgX • An ester than a formate with 2 moles of RMgX gives a 3° alcohol

38. Esters with RMgX • Steps 1 & 2

39. Esters with RMgX • Steps 3 & 4

40. Red'n - Esters by LiAlH4 • Most reductions of carbonyl compounds are now accomplished by hydride reducing agents • Esters are reduced by LiAlH4 to two alcohols • the alcohol derived from the carbonyl group is primary

41. Red'n - Esters by LiAlH4 • NaBH4 does not normally reduce esters, but it does reduce aldehydes and ketones • Selective reduction is often possible by the proper choice of reducing agents and experimental conditions

42. Red'n - Amides by LiAlH4 • LiAlH4 reduction of an amide gives a 1°, 2°, or 3° amine, depending on the degree of substitution of the amide

43. Interconversions • Problem: show reagents and experimental conditions to bring about each conversion

44. Carboxyl Derivatives End Chapter 13