HOAÙ HOÏC HÖÕU CÔ

1. HOAÙ HOÏC HÖÕU CÔ CHÖÔNG 12 ACID CARBOXYLIC Organic Chemistry

2. The Importance of Carboxylic Acids (RCO2H) • Starting materials for acyl derivatives (esters, amides, and acid chlorides) • Abundant in nature from oxidation of aldehydes and alcohols in metabolism • Acetic acid, CH3CO2H, - vinegar • Butanoic acid, CH3CH2CH2CO2H (rancid butter) • Long-chain aliphatic acids from the breakdown of fats

3. GIÔÙI THIEÄU

4. DANH PHAÙP

5. DANH PHAÙP

6. DANH PHAÙP

7. Alternative Names • Compounds with CO2H bonded to a ring are named using the suffix -carboxylic acid • The CO2H carbon is not itself numbered in this system • Use common names for formic acid (HCOOH) and acetic acid (CH3COOH) – see Table 20.1

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

9. Nomenclature of Acyl Halides • Name the acyl group and add the word chloride, fluoride, bromide, or iodide as appropriate. • Acyl chlorides are, by far, the most frequently encountered of the acyl halides

10. Nomenclature of Acyl Halides - Examples acetyl chloride 3-butenoyl chloride p-fluorobenzoyl bromide

11. Nomenclature of Acid Anhydrides • When both acyl groups are the same, name the acid and add the word anhydride • When the groups are different, list the names of the corresponding acids in alphabetical order and add the word anhydride

12. Nomenclature of Acid Anhydrides - Examples acetic anhydride benzoic anhydride benzoic heptanoic anhydride

13. Nomenclature of Acid Esters • name as alkyl alkanoates • cite the alkyl group attached to oxygen first (R') • name the acyl group second; substitute the suffix-ate for the -ic ending of the corresponding acid

14. Nomenclature of Acid Esters - Examples ethyl acetate methyl propanoate 2-chloroethyl benzoate

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

16. 4-hydroxy-2-methylpentanoic acid lactone -methyl--valerolactone => 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.

17. Nomenclature of Primary Amides • identify the corresponding carboxylic acid • replace the -ic acid or -oic acid ending by -amide

18. Nomenclature of Primary Amides - Examples acetamide 3-methylbutanamide benzamide

19. N-ethyl-N,2-dimethylpropanamide N-ethyl-N-methylisobutyramide => 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.

20. Nomenclature of Secondary & Tertiary Amides • name the amide as before • precede the name of the amide with the name of the appropriate group or groups • precede the names of the groups by the letter N- (standing for nitrogen and used as a locant) and

21. Nomenclature of Secondary & Tertiary Amides N-methylacetamide N,N-diethylbenzamide N-isopropyl-N-methylbutanamide

22. 4-aminopentanoic acid lactam -valerolactam => Cyclic Amides • Reaction of -NH2 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.

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

24. IR Spectroscopy => =>

25. 1H NMR Spectroscopy =>

26. 13C NMR Spectroscopy =>

27. => Interconversion ofAcid Derivatives • Nucleophile adds to the carbonyl to form a tetrahedral intermediate. • Leaving group leaves and C=O regenerates.

28. Reactivity Reactivity decreases as leaving group becomes more basic. =>

29. Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. =>

30. CAÙC PHÖÔNG PHAÙP TOÅNG HÔÏP

31. CAÙC PHÖÔNG PHAÙP TOÅNG HÔÏP

32. CAÙC PHÖÔNG PHAÙP TOÅNG HÔÏP

33. CAÙC PHÖÔNG PHAÙP TOÅNG HÔÏP

34. Carboxylation of Grignard Reagents

35. Mechanism of Grignard Carboxylation

36. CAÙC PHÖÔNG PHAÙP TOÅNG HÔÏP

37. CAÙC PHÖÔNG PHAÙP TOÅNG HÔÏP

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

39. Hydrolysis of Nitriles

40. CAÙC PHÖÔNG PHAÙP TOÅNG HÔÏP

41. => 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.

42. => Acid Hydrolysis of Esters • Reverse of Fischer esterification. • Reaches equilibrium. • Use a large excess of water.

43. 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(CH2)16CH3. =>

44. O O O Manufacture of Soap • Basic hydrolysis of the glyceryl triesters (from fats and oils) gives salts of long-chain carboxylic acids. • These salts are soaps. K2CO3, H2O, heat CH3(CH2)xCOK CH3(CH2)yCOK CH3(CH2)zCOK

45. •• •• O O •• •• – – •• •• •• •• + RCO + R' OH R'OH RCO •• •• •• •• •• •• Is the Mechanism BAL2 or BAC2? • One possibility is an SN2 attack by hydroxide on the alkyl group of the ester. Carboxylate is the leaving group. • This mechaism would be designated BAL2: • B (Basic conditions) • AL (Carbonyl-OAlkyl bond breaking in rate-determining step) • 2 (Reaction is second order - rate = k[ester][hydroxide]

46. •• •• O O •• •• – – •• •• •• •• RC OR' OH OR' RC OH •• •• •• •• •• •• Is the Mechanism BAL2 or BAC2? • A second possibility is nucleophilic acyl substitution. + +

47. O + CH3CH2COCH2CH3 NaOH O + CH3CH2CONa CH3CH2OH 18O Labeling gives the answer • 18O retained in alcohol, not carboxylate; therefore nucleophilic acyl substitution.

48. •• •• O O •• •• – – •• •• •• •• RC OR' OH OR' RC OH •• •• •• •• •• •• Does it proceed via a tetrahedral intermediate? • Does nucleophilic acyl substitution proceed in a single step, or is a tetrahedral intermediate involved? + +

49. O COCH2CH3 O COCH2CH3 18O Labeling Studies + H2O • Ethyl benzoate, labeled with 18O at the carbonyl oxygen, was subjected to hydrolysis in base. • Ethyl benzoate, recovered before the reaction had gone to completion, had lost its 18O label. • This observation is consistent with a tetrahedral intermediate. HO– + H2O

50. O COCH2CH3 OH OCH2CH3 C OH O COCH2CH3 18O Labeling Studies + H2O HO– HO– + H2O