CARBOXYLIC ACID DERIVATIVES Chapter-21

1. CARBOXYLIC ACID DERIVATIVES Chapter-21 Farshid Zand

2. Carboxylic Acid Derivatives Ester Farshid Zand

3. Carboxylic Acids • The primary suffix name for a carboxylic acid is based on the "longest carbon chain name *"+"oic acid" for the COOH acidic bond system • Ex. methanoic acid, ethanoic acid Farshid Zand

4. Naming of Acid Halides • Identify the acyl group first, followed by identification of the halide. • Replace the –ic acid suffix of carboxylic acids with –yl. • If the acyl group is a branch of a cyclic compound, replace the ending from carboxylic acid to -carbonyl. Farshid Zand

5. Acetal Chloride Benzoyl Bromide Examples of Acid Halides Farshid Zand

6. Naming of Acid Anhydrides • Unsubstituted monocarboxylic acids and cyclic anhydrides of dicarboxylic acids are named by replacing the word acid with anhydride. Acetic Anhydride Farshid Zand

7. Substituted monocarboxylic are named by adding the prefix bis- to the acid name. Naming of Acid Anhydrides Bis(chloroacetic) anhydride Farshid Zand

8. Naming of Acid Anhydrides • Unsymmetrical anhydrides are those composed of two different carboxylic acids. • They are named alphabetically. Acetic benzoic anhydride Farshid Zand

9. Naming of Esters • Identify the alkyl group attached to the oxygen, then the carboxylic acid. The –ic acid suffix is replaced with –ate. Ethyl-4-pentenoate Farshid Zand

10. Naming of Amides • An unsubstituted –NH2 group is named by replacing the –oic acid of the carboxylic acid with –amide and –carboxylic acid with –carboxamide. • A substituted compound is named by identification of the substituents followed by the parent amide • Each substituent is preceded by the letter N Farshid Zand

11. Example of Amides N,N-dimethyl-3-acetylbenzamide Acetamide Farshid Zand

12. Nuclephilic Acyl Substitution • the major reaction of carboxyl derivatives • starts like nucleophilic addition, but becomes substitution when the leaving group departs • the tetrahedral intermediate is like that of carbonyl additions • the product is often another carboxyl derivative(depending on what the nucleophile is) Farshid Zand

13. Nucleophilic Acyl Substitution Y is a leaving group: -OR, -NR2, -Cl Farshid Zand

14. Types of Nucleophilic Acyl Substitution • Hydrolysis: Reaction with water to create carboxylic acids • Alcoholysis: Reaction with alcohol to yield an ester • Aminolysis: Reaction with ammonia or an amine to yield an amide • Reduction: Reaction with a hydride reducing agent to create an anhydride or an alcohol • Grignard: Reaction with an organometallic reagent to yield a ketone or an alcohol Farshid Zand

15. Comparison to other Nucleophilic Substitutions: • SN2 - simultaneous bonding of nucleophile and loss of leaving group • SN1 - first loss of leaving group, then bonding of nucleophile (cation intermediate) • Acyl - first bonding of nucleophile, then loss of leaving group (anion intermediate) Farshid Zand

16. Reactivity in Acyl Nucleophilic Substitution • better leaving groups increase reactivityacid halides > acid anhydrides > esters > amides • reactive derivatives can be easily converted to the others • all the derivatives can be hydrolyzed to the carboxylic acid (water as the nucleophile - using acid or base catalysis) Farshid Zand

17. REACTIVITY LESS REACTIVE MORE REACTIVE AMIDE < ESTER < ACID ANHYDRIDE < ACID HALIDE Farshid Zand

18. Base-induced Ester Hydrolysis • Base promotes hydrolysis of esters by providing the strongly nucleophilic reagent OH-.  This reaction is essentially irreversible, since a resonance-stabilized carboxylate anion shows little tendency to react with an alcohol.  Thus, basic hydrolysis of esters has a large equilibrium constant and it is sufficient to use only one equivalent of water in order for the reaction to proceed to completion. Farshid Zand

19. HYDROLYSIS: Conversion of Acid Halides into Alcohols :Base Farshid Zand

20. ALCOHOLYSIS: Conversion of Acid Halides into Esters Pyridine Benzoyl Chloride Cyclohexanol Cyclohexyl benzoate Farshid Zand

21. AMINOYLSIS : Conversion of Acid Halides into Amides N,N-Dimethylbenzamide Benzoyl Chloride Farshid Zand

22. REDUCTION: Conversion of Acid Chlorides into Alcohols Farshid Zand

23. Reaction of Acid Chlorides with Organometallic Reagents Farshid Zand

24. Preparation of Acid Anhydrides The most general method for the preparing an acid anhydride is by nucleophilic acyl substitution reaction of an acid chloride with a carboxylate anion. Farshid Zand

25. Reactions of Acid Anhydrides The chemistry of acid anhydrides is similar to that of acid chlorides. The anhydrides react slower than acid chlorides, but the kinds of reactions the two groups have are the same Farshid Zand

26. Preparation of Esters • conversion to esters with alcohol and acid catalysis(Fisher esterification method) a reversible equilibriumfavored to the right with excess alcoholfavored to the left with excess water (hydrolysis) Farshid Zand

27. BASE CATAYLZED ESTER HYDROLYSIS _ + + Farshid Zand

28. ACID CATALYZED ESTER HYDROLYSIS + R’OH + H3O+ Farshid Zand

29. AMINOLYSIS: Conversion of Esters into Amides Farshid Zand

30. REDUCTION: Conversion of Esters into Alcohols Farshid Zand

31. Reaction of Esters with Grignard Reagents Farshid Zand

32. REDUCTION: Conversion of Amides into Amines Farshid Zand

33. Reactions of Acyl Chlorides Farshid Zand

34. Reactions of Acid Anhydrides Farshid Zand

35. Reactions of Esters Farshid Zand

36. Reactions of Esters Farshid Zand

37. Reactions of Amides + Farshid Zand