Organic Chemistry

1. Organic Chemistry William H. Brown & Christopher S. Foote

2. Carboxyl Derivatives

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

4. Carboxyl Derivatives • an amide is formally related to a carboxyl group by loss of -OH from the carboxyl and -H from ammonia • loss of -OH and -H from an amide gives a nitrile

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

6. Acid Chlorides • replacement of -OH in a sulfonic acid by -Cl gives a sulfonyl chloride

7. 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, replace acid of the parent acid by anhydride

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

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

10. 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 followed by the name of the acid • change the suffix -ic acid to -ate

11. Esters • Cyclic esters are called lactones • name the parent carboxylic acid, drop the suffix -ic acid, and add -olactone

12. Amides • The functional group of an amide is an acyl group bonded to a nitrogen atom • IUPAC: drop -oic acidfrom 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. Penicillins • The penicillins are a family of -lactam antibiotics

15. Penicillins • Amoxicillin

16. Cephalosporins • The cephalosporins are also -lactam antibiotics

17. Cefetamet

18. Nitriles • The functional group of a nitrile is a cyano group • IUPAC: name as an alkanenitrile • Common: drop the -ic acidand add -onitrile

19. Acidity of N-H bonds • Amides are comparable in acidity to alcohols • water-insoluble amides do not react with NaOH or other alkali metal hydroxides to form water soluble salts • Sulfonamides and imides are more acidic than amides

20. Acidity of N-H bonds • Imides are more acidic than amides because 1. the electron-withdrawing inductive of the two adjacent C=O groups weakens the N-H bond, and 2. the imide anion is stabilized by resonance delocalization of the negative charge

21. Acidity of N-H • imides such as phthalimide readily dissolve in aqueous NaOH as water-soluble salts

22. IR Spectroscopy

23. NMR Spectroscopy • 1H-NMR • H on the -carbon to a C=O group are slightly deshielded and come into resonance at  2.1-2.6 • H on the carbon of the ester oxygen are more strongly deshielded and come into resonance at  3.7-4.7 • 13C-NMR • the carbonyl carbons of esters show characteristic resonance at  160-180

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

25. Characteristic Reactions • in this general reaction, we have shown the leaving group as an anion to illustrate an important point about them: the weaker the base, the better the leaving group

26. 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

27. 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

28. Rexn with H2O - RCO2OR • 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

29. 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 role of the acid catalyst is to protonate the carbonyl oxygen and increase its electrophilic character toward attack by water to form a tetrahedral carbonyl addition intermediate • collapse of this intermediate gives the carboxylic acid and alcohol

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

31. Rexn with H2O - Esters • Hydrolysis of an esters in aqueous base is often called saponification • each mole of ester hydrolyzed requires 1 mole 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

32. Rexn with H2O - Amides • Hydrolysis of an amide in aqueous acid requires 1 mole of acid per mole of amide

33. Rexn with H2O - Amides • Hydrolysis of an amide in aqueous base requires 1 mole of base per mole of amide

34. Rexn with H2O - Nitriles • The cyano group is hydrolyzed in aqueous acid to a carboxyl group and ammonium ion

35. Rexn with H2O - Nitriles • protonation of the cyano nitrogen gives a cation that reacts with water to give an imidic acid • keto-enol tautomerism of the imidic acid gives the amide

36. Rexn with H2O - Nitriles • hydrolysis of a cyano group in aqueous base gives a carboxylic anion and ammonia; acidification converts the carboxylic anion to the carboxylic acid

37. Rexn with H2O - Nitriles • Hydrolysis of nitriles is a valuable route to carboxylic acids

38. Rexn with Alcohols • Acid halides react with alcohols to give esters • acid halides are so reactive toward even weak nucleophiles such as alcohols that no catalyst is necessary • where the alcohol or resulting ester is sensitive to HCl, reaction is carried out in the presence of a 3° amine to neutralize the acid

39. Rexn with Alcohols • sulfonic acid esters are prepared by the reaction of an alkane- or arenesulfonyl chloride with an alcohol or phenol

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

41. Rexn with Alcohols • cyclic anhydrides react with alcohols to give one ester group and one carboxyl group

42. Rexn with Alcohols • aspirin is synthesized by treatment of salicylic acid with acetic anhydride

43. Rexn with Alcohols • Esters react with alcohols in the presence of an acid catalyst in a reaction called transesterification, an equilibrium reaction

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

45. 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

46. 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

47. Interconversions

48. Acid Chlorides with Salts • Acid chlorides react with salts of carboxylic acids to give anhydrides • most commonly used are sodium or potassium salts

49. Rexns with Grignards • treatment of a formic ester with 2 moles of Grignard reagent followed by hydrolysis with aqueous acid gives a 2° alcohol

50. Rexn with Grignards • treatment of an ester other than formic with a Grignard reagent followed by hydrolysis in aqueous acid gives a 3° alcohol