1. 13 13-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown

2. 13 13-2 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Chapter 13 CarboxylDerivatives

3. 13 13-3 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 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. 13 13-4 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure: Acid Chlorides The functional group of an acid halide is an acyl group bonded to a halogen -ic acid -yl halide to name, change the suffix -ic acid to -yl halide

5. 13 13-5 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 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) acidanhydride to name, replace acid of the parent acid by anhydride

6. 13 13-6 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acid Anhydrides Cyclic anhydrides are named from the dicarboxylic acids from which they are derived

7. 13 13-7 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acid Anhydrides A phosphoric acid anhydride contains two phosphoryl groups bonded to an oxygen atom

8. 13 13-8 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Esters The functional group of an ester is an acyl group bonded to -OR or -OAr -ic acid ate 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. 13 13-9 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Lactones Cyclic esters are called lactones -ic acidolactone Name the parent carboxylic acid, drop the suffix -ic acid, and add -olactone

10. 13 13-10 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 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. 13 13-11 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Phosphoric Esters to name more complex phosphoric esters, name the organic molecule followed by the name phosphate

12. 13 13-12 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Amides The functional group of an amide is an acyl group bonded to a nitrogen atom -oic acid amide to name, drop -oic acid from the name of the parent acid and add -amide N if the amide nitrogen is bonded to an alkyl or aryl group, name the group and show its location on nitrogen by N-

13. 13 13-13 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Amides Cyclic amides are called lactams -ic acidlactam name the parent carboxylic acid, drop the suffix -ic acid, and add -lactam

14. 13 13-14 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Amides The penicillins are a family of  -lactam antibiotics

15. 13 13-15 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Penicillin G

16. 13 13-16 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Amides The cephalosporins are also  -lactam antibiotics

17. 13 13-17 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Cefetamet

18. 13 13-18 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Characteristic Reactions Nucleophilic acyl substitution Nucleophilic acyl substitution: an addition- elimination sequence resulting in substitution of one nucleophile for another

19. 13 13-19 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Characteristic Reactions The leaving group as an anion, Y -, to illustrate an important point: the weaker the base, the better the leaving group

20. 13 13-20 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 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. 13 13-21 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with H 2 O - 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. 13 13-22 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with H 2 O - 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. 13 13-23 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with H 2 O - 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. 13 13-24 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with H 2 O - Esters Acid-catalyzed ester hydrolysis

25. 13 13-25 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with H 2 O - Esters saponification 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. 13 13-26 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with H 2 O - Esters base-promoted ester hydrolysis

27. 13 13-27 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with H 2 O - Amides hydrolysis of an amide in aqueous acid requires 1 mol of acid per mol of amide

28. 13 13-28 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with H 2 O - Amides hydrolysis of an amide in aqueous base requires 1 mol of base per mol of amide

29. 13 13-29 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 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. 13 13-30 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with Alcohols Acid anhydrides react with alcohols to give one mol of ester and one of carboxylic acid

31. 13 13-31 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexn with Alcohols Synthesis of aspirin synthesized

32. 13 13-32 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 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. 13 13-33 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 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. 13 13-34 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 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. 13 13-35 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Interconversion Relative reactivities of carboxyl derivatives

36. 13 13-36 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Esters with RMgX A formic ester with 2 moles of RMgX followed by hydrolysis gives a 2° alcohol

37. 13 13-37 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Esters with RMgX An ester than a formate with 2 moles of RMgX gives a 3° alcohol

38. 13 13-38 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Esters with RMgX Steps 1 & 2

39. 13 13-39 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Esters with RMgX Steps 3 & 4

40. 13 13-40 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Red'n - Esters by LiAlH 4 Most reductions of carbonyl compounds are now accomplished by hydride reducing agents Esters are reduced by LiAlH 4 to two alcohols the alcohol derived from the carbonyl group is primary

41. 13 13-41 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Red'n - Esters by LiAlH 4 NaBH 4 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. 13 13-42 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Red'n - Amides by LiAlH 4 LiAlH 4 reduction of an amide gives a 1°, 2°, or 3° amine, depending on the degree of substitution of the amide

43. 13 13-43 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Interconversions Problem Problem: show reagents and experimental conditions to bring about each conversion

44. 13 13-44 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. CarboxylDerivatives End Chapter 13