1. Carboxylic acids and their derivatives
Synthesis of acids
Properties of acids
Nomenclature of acids
Reactions of acids
Acid derivatives and their properties
Nomenclature of acid derivatives
Reactions of acid derivatives

2. Carboxylic acids
The carboxylic acid functional group consist of a carbonyl group that has a hydroxyl group attached to the carbonyl carbon.
Carboxylic acid groups are generally written as R-COOH or
R-CO2H
Carboxylic acids are generally weak acids that are only partially ionized.
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3. Properties of carboxylic acids
Boiling Points
Higher boiling points than similar alcohols, due to dimer formation.
Acetic acid, b.p. 118C
Melting Points
Aliphatic acids with more than 8 carbons are solids at room temperature.
Double bonds (especially cis) lower the melting point. Note these 18-C acids:
Stearic acid (saturated): 72C
Oleic acid (one cis double bond): 16C
Linoleic acid (two cis double bonds): -5 (cis,cis-9,12-octadecadienoic acid)

4. Properties of carboxylic acids
Solubility
Water solubility decreases with the length of the carbon chain.
Up to 4 carbons, acid is miscible in water.
More soluble in alcohol.
Also soluble in relatively nonpolar solvents like chloroform because it dissolves as a dimer.

5. Acidity

6. Structure of Carboxyl Carbon is sp2 hybridized.
Bond angles are close to 120.
O-H eclipsed with C=O, to get overlap of  orbital with orbital of lone pair on oxygen.

7. Substituent Effects on Acidity
Acid + Base salt + “water”

8. Naming Carboxylic acids
Historical names are commonly used for many carboxylic acids.
Positions of substituents on the chain are labeled with Greek letters.

9. Common Carboxylic acid Names
formic acid acetic acid propionic acid butyric acid
Benzoic acid phthalic acid

10. Common Carboxylic acid Names
oxalic acid malonic acid succinic acid
adipic acid IUPAC: hexanedioic acid

11. Naming Carboxylic acids
IUPAC Names
Remove -e from alkane (or alkene) name, add -oic acid. The carboxylic acid group has priority over all over groups.
The carbon of the carboxyl group is #1.
2-chlorobutanoic acid
trans-3-phenyl-2-propenoic acid (cinnamic acid)

12. o-hydroxybenzoic acid
Naming Cyclic Acids
When the -CO2H is bonded to a cycloalkane ring the compound is named as a cycloalkanecarboxylic acids.
Aromatic acids are named based on benzoic acids.
o-hydroxybenzoic acid
(salicylic acid)
2-isopropylcyclopentanecarboxylic acid

13. Dicarboxylic Acids
Aliphatic diacids are usually called by their common names (to be memorized).
For IUPAC name, number the chain from the end closest to a substituent.
Two carboxyl groups on a benzene ring indicate a phthalic acid.
3-bromohexanedioic acid
-bromoadipic acid
1,3-benzenedicarboxylic acid
m-phthalic acid

14. Common Carboxylic acid Names
Long chain carboxylic acids are called fatty acid. Fatty acids are generally found as ester in nature.
Fat - a triglyceride - three fatty acids esterified to glycerol (propane-1,2,3-triol) - that is solid at room temperature. Generally animal source. Fatty acid chains are generally saturated.
Oil - a triglyceride that is liquid at room temperature. Generally plant source. Fatty acid chains are generally unsaturated.
See handout for the composition of different fats and oils.

15. Common Carboxylic acid Names
For fatty acids containing double bonds, the location of the double bond is sometimes specified relative to the last carbon in the chain - the omega () carbon.
Linoleic acid (an -6 fatty acid)
Alpha-linolenic acid (an -3 fatty acid)

16. Common Carboxylic acid Names
A deprotonated acid is a carboxylate ion. The -oic acid becomes -oate in the deprotonated form. The name of the metal counterion comes first in the compound name.
Acetic acid
Sodium acetate
Sodium benzoate
benzoic acid

17. Acidity of Carboxylic acids
[RCOO][H+]
Ka =
[RCOOH]
The larger the Ka values the stronger the acid.
Since most carboxylic acids have small Ka values (104 and lower), acid strength is often expressed using pKa values.

18. Strong acids have small pKas
Acidity of Carboxylic acids
pKa = log Ka
pKa and acid strength are inversely related
Strong acids have small pKas
Most carboxylic acids have pKa vales in the 4.0 to 5.0 range.
HCOOH pKa = 3.75
CH3COOH pKa = 4.74
Benzoic acid pKa = 4.19

20. Acidity of Carboxylic acids
Which to the stronger acid?
pKa

21. Acidity of Carboxylic acids
The proximity of electron withdrawing groups has an effect.
pKa = 2.86
pKa = 4.52

22. Acid-Base reaction

24. spectroscopy of carboxylic acids
C=O of COOH cm1 (conjugation lowers )
-O-H stretch of carboxylic acid cm1
-O-H stretch of alcohol cm1
( cm1)

25. Proton NMR
10-12 ppm
1.0
1.6
2.4
13C-NMR 34 31
181 ppm 22 25 14

26. Synthesis of acids

27. Synthesis of acids

28. Synthesis of acids

29. Synthesis of acids

30. Synthesis of acids
Nitriles can undergo either acid or base catalyzed hydrolysis to form carboxylic acids or carboxylates.
Nitriles can easily be prepared from the corresponding halides.

31. Synthesis of acids Malonic ester synthesis: Diethyl malonate
This second step is a decarboxylation reaction.

32. Synthesis of acids

33. Synthesis of acids Commercial sources
Many carboxylic acids are derived commercially from natural sources. Straight chain acid with 6 to 18 are readily obtained from fats and oil. Fats and oils are composed of triesters of glycerol (triglyceride). The acid is obtained by either acid or base hydrolysis of the ester groups. The base hydrolysis is called saponification (the making of soap) produces the carboxylate salt. Acid hydrolysis gives the free acid.

34. Synthesis of acids Commercial sources
Acetic acid is produced via both fermentation and catalytic processes.
Other acids such as benzoic acid, phthalic acid and adipic acid are produced via oxidation of an appropriate substrate.

35. Reactions of acids
The reactivity of these acid derivatives is dependent on the basicity of the leaving group. (List the leaving groups in order of increasing basicity.)

36. Synthesis of acid chlorides

37. Synthesis of esters from acids
Ester synthesis

38. Esterification under acid conditions (Fischer esterification)

39. Esterification using diazomethane
Yields of the methyl ester are very good. However, diazomethane is a toxic, explosive gas. The reagent is generated just before it is used. Ether solutions of this reagent are relatively safe to work with.

40. Ester from acid Chlorides
What is the mechanism for this reaction?

41. Synthesis of amide from acids
The initial formation of the ammonium carboxylate salt is an exothermic reaction. The reaction mixture is then typically heated to °C to convert the salt to the amide with loss of water.

42. Synthesis of amide from acid chlorides
The HCl that is generated by this reaction must be neutralized or scavenged from the reaction mixture to prevent the protonating of unreacted amine. This is often done with pyridine, NaOH or Na2CO3. The reaction must be kept dry since acid chloride will react with water to give the acid.

43. Synthesis of acid anhydrides
Acid anhydrides react similarly to acid chlorides to form esters and amides.

44. Reduction of Acids
Note that esters undergo an analogous reaction with LAH.

45. Reduction of Acid Chlorides

46. Nomenclature and reactions of acid derivatives

47. Naming Esters Esters are named as alkyl carboxylates.
Alkyl from the alcohol, carboxylate from the carboxylic acid precursor.

48. 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.
4-hydroxybutanoic acid lactone
γ -hydroxybutyrolactone
4-hydroxybutanoic acid
γ-hydroxybutyric acid

49. Reactions of Esters
transesterification
saponificaton

50. Amides
Product of the reaction of a carboxylic acid and ammonia or an amine.
Not basic because the lone pair on nitrogen is delocalized by resonance.

51. Classes of Amides 1 amide has one C-N bond (two N-H).
2 amide or N-substituted amide has two C-N bonds (one N-H).
3 amide or N,N-disubstituted amide has three C-N bonds (no N-H).

52. Classes of Amides
DMF is a common polar and aprotic solvent that is often used in the laboratory. Because of the very strong hydrogen bonding in 1° and 2° amides they have very high melting and boiling points.

53. 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.
N-ethyl-N,2-dimethylpropanamide
N-ethyl-N-methylisobutyramide

54. 4-aminobutanoic acid lactam
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.
4-aminobutanoic acid lactam
-butyrolactam

55. Reactions of Amides
(only work with 1 amides)

56. Naming Nitriles For IUPAC names, add -nitrile to the alkane name.
Common names come from the carboxylic acid. Replace -ic acid with -onitrile.
5-bromohexanenitrile
-bromocapronitrile
Cyclohexanecarbonitrile

57. Nitriles synthesis
Unlike other acid derivatives nitriles do not contain a carbonyl.
Nitriles can be prepared by treating an amide with POCl3 or at high temperature over an alumina catalyst.

58. Reactions of Nitriles
(Note: shorter periods of hydrolysis can yield an intermediate amide)

59. Acid Halides Named by replacing -ic acid with -yl halide.
3-bromobutanoyl bromide
-bromobutyryl bromide
benzoyl chloride

60. Acid Halides
(Pyridine or NaHCO3(aq) is used to help control acidity since protonating the N stops the reaction.

61. To name an anhydride drop the word acid and replace with anhydride.
Acid Anhydrides
Two molecules of acid combine with the loss of water to form the anhydride.
A carboxylate ion is the leaving group in nucleophilic acyl substitution reactions.
To name an anhydride drop the word acid and replace with anhydride. R C O H

62. 1,2-benzenedicarboxylic anhydride
Acid Anhydrides
ethanoic anhydride
acetic anhydride
1,2-benzenedicarboxylic anhydride
phthalic anhydride

63. Acid Anhydrides
(Note: The benzene ring cannot be strongly deactivated.)

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

65. Solubility
Acid chlorides and anhydrides are too reactive to be used with water or alcohol.
Esters, 3 amides, and nitriles are good polar aprotic solvents.
Solvents commonly used in organic reactions:
Ethyl acetate
Dimethylformamide (DMF)
Acetonitrile

69. 1H NMR Spectroscopy

70. 13C NMR Spectroscopy

74. Acid Chloride to Anhydride
Acid or carboxylate ion attacks the C=O.
Tetrahedral intermediate forms.
Chloride ion leaves, C=O is restored, H+ is abstracted.

75. Acid Chloride to Ester Alcohol attacks the C=O.
Tetrahedral intermediate forms.
Chloride ion leaves, C=O is restored, H+ is abstracted.

76. Acid Chloride to Amide Ammonia yields a 1 amide
A 1 amine yields a 2 amide
A 2 amine yields a 3 amide

77. Anhydride to Ester
Alcohol attacks one C=O of anhydride.
Tetrahedral intermediate forms.
Carboxylate ion leaves, C=O is restored, H+ is abstracted.

78. Anhydride to Amide
Ammonia yields a 1 amide
A 1 amine yields a 2 amide
A 2 amine yields a 3 amide

79. Ester to Amide Nucleophile must be NH3 or 1 amine.
Prolonged heating required.

80. Transesterification
One alkoxy group can be replaced by another with acid or base catalyst.
Use large excess of preferred alcohol.