1. Carboxylic acids and derivatives
Dr. Sheppard
CHEM 2412
Summer 2015
Klein (2nd ed.) sections: 21.1, 21.2, 21.6, 21.3, 21.15,
21.4, 21.5, 21.10, 21.7, 21.8,
21.9, 21.11, 21.12, 21.13, 21.14

2. Carboxylic Acids and Derivatives
Found in nature
Carboxylic acid derivatives:

3. Carboxylic Acids and Derivatives
Nomenclature Review
Physical Properties
Acidity of Carboxylic Acids
Spectroscopy
Preparation of Carboxylic Acids
Reactions of Carboxylic Acids
Nucleophilic Acyl Substitution

4. I. Nomenclature (Review)
Carboxylic acids
Parent chain contains carbon of –CO2H
Suffix is “-oic acid”
–CO2H is carbon 1
Cyclic molecules with –CO2H substituents
–CO2H is bonded to carbon 1 of ring
Add “carboxylic acid” to end of ring parent name

5. Examples
Structure
Name

6. Naming Acid Chlorides Name corresponding carboxylic acid
Change “-ic acid” to “-yl chloride”
Examples:
Structure
Name

7. Naming Acid Anhydrides
If R = R’, name carboxylic acid RCO2H. Replace “acid” with “anhydride”
If R ≠ R’, list the two acids alphabetically and add the word “anhydride”
Examples:
Structure
Name

8. Naming Esters Name alkyl group bonded to oxygen (R’)
Name carboxylic acid RCO2H
Change “-ic acid” to “-ate”
Examples:
Structure
Name

9. Naming Amides Name corresponding carboxylic acid
Change “-oic acid” to “-amide”
Examples:
Structure
Name

10. Naming Nitriles Two methods
Nitrile carbon is carbon 1 of parent chain. Add “-nitrile” to end of alkane name.
Name as carboxylic acid derivative. Replace “-ic acid” with “-onitrile”

11. II. Physical Properties
Carboxylic acids form a hydrogen bond dimer
Boiling points
Carboxylic acids are very high
CA > alcohols > aldehyde/ketones > hydrocarbons
Carboxylic acid derivatives are less predictable
Generally amides > carboxylic acids > acid halides/esters
Tertiary amides < primary and secondary amides
no H-bonding in liquid phase (neat)

12. II. Physical Properties
Solubility in water
Low MW CAs and CADs are soluble
Solubility decrease as MW increases
Salts of carboxylic acids are more soluble
CADs also react with water (to form carboxylic acids)
Odor
Esters = sweet or floral
Carboxylic acids = unpleasant

13. III. Acidity of Carboxylic Acids
Weak acids (pKa ~ 4-5)
Stronger than alcohols because conjugate base is resonance-stabilized

14. III. Acidity of Carboxylic Acids
Conjugate base can be further stabilized if electronegative atom is present
Inductive effect
Position of en atom affects pKa

15. III. Acidity of Carboxylic Acids
Substituted benzoic acids
If Z = electron-donating group, acid is weaker
If Z = electron-withdrawing group, acid is stronger

16. IV. Spectroscopy of CAs: IR
Absorption at cm-1 for COOH
Absorption at cm-1 for C=O

17. IV. Spectroscopy of CAs: NMR
13C-NMR:
1H-NMR:
COOH signal d11-12

18. IV. Spectroscopy of CADs: IR
Absorption at cm-1 for C=O

19. IV. Spectroscopy of CADs: NMR
13C-NMR:
Carbonyl carbon slightly upfield from aldehydes and ketones
1H-NMR:
H adjacent to C=O around d2, but doesn’t always help you determine functional group
Look for OH (CA), NH (amide), or OR (ester)

20. V. Preparation of Carboxylic Acids
Oxidation of primary alcohols and aldehydes (section 13.10)

21. V. Preparation of Carboxylic Acids
Oxidative cleavage of alkenes or alkynes (section 10.9)

22. V. Preparation of Carboxylic Acids
Oxidation of alkylbenzenes
We will see this in the aromatic chapters

23. V. Preparation of Carboxylic Acids
Hydrolysis of nitriles
Requires aqueous acid and heat

24. V. Preparation of Carboxylic Acids
Carboxylation of Grignard reagents
Addition of CO2, followed by H3O+
Mechanism:
Example:

25. Show two methods that could be used to make butanoic acid from 1-bromopropane

26. VI. Reactions of Carboxylic Acids
Types of reactions
Deprotonation
a-Substitution
Oxidation?
Reduction?
Conversion to CADs

27. Reduction Need a strong reducing agent Reduce to primary alcohol LAH
Remember reducing agent chart from alcohol chapter

28. Conversion to CADs Fischer esterification
Carboxylic acid + alcohol → ester + water
Needs acid catalyst (H2SO4 or HCl)
Reaction is reversible
Push to the right with excess alcohol or remove water

29. Conversion to CADs Formation of acid chlorides Reagent = SOCl2
Where have we seen this reagent before?

30. Conversion to CADs Formation of acid anhydrides
Anhydride = without water
Apply heat to carboxylic acids to remove water

31. Conversion to CADs Formation of amides
Reaction is difficult with N nucleophile because the N (base) reacts with the carboxylic acid (acid)

32. VII. Nucleophilic Acyl Substitution
Include all of the CA → CAD reactions
Also used to make CAs from CADs and convert between CADs
Z is leaving group
Compare to nucleophilic addition (aldehydes/ketones)

33. VII. Nucleophilic Acyl Substitution
Mechanism
Acid or base catalyst typically needed
Acid makes electrophile more electrophilic
Base makes nucleophile more nucleophilic

34. VII. Nucleophilic Acyl Substitution
Reactivity:
Less substituted molecules are more reactive

35. VII. Nucleophilic Acyl Substitution
Reactivity:
Molecules with better leaving groups are more reactive
Less reactive compounds need heat or catalyst to react and are limited in the number of reactions they will undergo
Example: amides only undergo hydrolysis and reduction

36. VII. Nucleophilic Acyl Substitution
Reactivity:
More reactive compounds can be converted to less reactive compounds
Can an ester be converted into an amide?
Can an amide be converted into an ester?

37. VII. Nucleophilic Acyl Substitution
Types of reactions

38. VII. Nucleophilic Acyl Substitution
Types of reactions:
Reaction
Nucleophile
Product
Special Notes
Hydrolysis
H2O
Carboxylic acid
Alcoholysis
ROH
Ester
Aminolysis
NH3
1° amine
2° amine
1° amide
2° amide
3° amide
With acid chlorides, 2 eq. of amine are needed:
the nucleophile
neutralizes HCl byproduct
Reduction
Hydride from LAH
CA → 1° ROH
Ester → 1° ROH
Anhydride → 1° ROH
Acid chloride → 1° ROH
Amides → amines
Hydride from DIBALH
aldehyde
Ester only
Grignard
RMgX
3° alcohol
Ester and acid halide only

39. VII. Nucleophilic Acyl Substitution
Summary of reactions: acid halide
Also Grignard
Anhydride formation:

40. VII. Nucleophilic Acyl Substitution
Summary of reactions: anhydrides
Example: commercial preparation of aspirin

41. VII. Nucleophilic Acyl Substitution
Summary of reactions: esters
Hydrolysis
Alcoholysis
Aminolysis
Reduction (to 1° alcohols and aldehydes)
Grignard
Alcoholysis of esters = transesterification

42. VII. Nucleophilic Acyl Substitution
Summary of reactions: amides
Hydrolysis
Acid or base catalyst
Heat
Reduction

43. VII. Nucleophilic Acyl Substitution
Summary of reactions: nitriles
Hydrolysis
Acid or base catalyst
Heat
Reduction

44. VII. Nucleophilic Acyl Substitution
Complete the chart with the functional group that will form from the following reactions.
H2O
ROH
NH3
LAH
Grignard
Carboxylic acid
Acid halide
Acid anhydride
Ester
Amide
Nitrile

45. VII. Nucleophilic Acyl Substitution
Specific reactions:
Saponification (soap-making)
Hydrolysis of ester in base
Irreversible reaction

46. VII. Nucleophilic Acyl Substitution
Condensation polymerization
A step-growth reaction
Example: polyamide
What is a polyester? How could a polyester be synthesized?

47. VII. Nucleophilic Acyl Substitution
Step-growth polymerization
Compare Fischer esterification…
…to polymerization

48. VII. Nucleophilic Acyl Substitution
Step-growth polymerization
Biodegradable polymers

49. What is the order of decreasing activity (most reactive = 1, least reactive = 4) toward nucleophilic acyl substitution for the following carboxylic acid derivatives?

50. Draw the products of these reactions.

51. Synthesis
Propose a synthesis for ethyl acetate from ethanol.

52. Provide reagents to complete the reaction scheme

53. Provide reagents for the following reactions: