CARBOXYLIC ACIDS AND NITRILES
Chapters 20, 21 Organic Chemistry, 8th Edition John McMurry
1 CARBOXYLIC ACID DERIVATIVES
2 CARBOXYLIC ACID DERIVATIVES
R C N
nitrile R = CH3 acetonitrile 3 STRUCTURE AND BONDING
4 NOMENCLATURE—THE IUPAC SYSTEM
heptanoic acid benzoic acid cyclopentane carboxylic acid
4,5-dimethyl 3-pentenoic 3-bromobenzoic p-toluic 1-methyl- hexanoic acid acid acid acid cyclopropanecarboxylic acid
5 NOMENCLATURE-COMMON NAMES
προτοσ πιον
6 NOMENCLATURE-POLYIACIDS
Oxalis acetosella Malon Succinum
HOOC COOH
COOH propane-1,2,3-tricarboxylic acid 7 PHYSICAL PROPERTIES • Carboxylic acids exhibit dipole-dipole interactions because they have polar C—O and O—H bonds.
• They also exhibit intermolecular hydrogen bonding.
• In the gas phase and in apolar solvents, carboxylic acids often exist as dimers held together by two intermolecular hydrogen bonds.
8 PHYSICAL PROPERTIES
9 ACIDITY OF CARBOXYLIC ACIDS
The acetate anion has two C—O bonds of equal length (1.27 Å) and intermediate between the length of a C—O single bond (1.36 Å) and C=O (1.21 Å).
10 CARBOXYLIC ACIDS—STRONG ORGANIC BRØNSTED-LOWRY ACIDS
11 THE INDUCTIVE EFFECT IN ALIPHATIC CARBOXYLIC ACIDS
12 THE INDUCTIVE EFFECT IN ALIPHATIC CARBOXYLIC ACIDS
13 SUBSTITUTED BENZOIC ACIDS
14 SUBSTITUTED BENZOIC ACIDS
15 PREPARATION OF CARBOXYLIC ACIDS [1] Oxidation of 1° alcohols
[2] Oxidation of alkyl benzenes
16 PREPARATION OF CARBOXYLIC ACIDS
[3] From alkyl halides CN
CN- i. NaOH + ii.H3O
Br COOH
i. CO2 Mg + ii. H3O MgBr
R MgBr R OMgBr H O+ R OH 3 + Mg++ + Br- O C O O O
17 PREPARATION OF CARBOXYLIC ACIDS
[5] From alkyl halides. Malonic ester synthesis
a) Acidity of malonate esters O O- O EtOOC EtO EtO EtO pKa 13 EtOOC EtO EtO EtO O O O-
b) Synthesis - Br i. OH EtOOC - EtOOC EtOOC ii. H+, ΔΔ EtO HOOC EtOOC EtOOC COOEt
c) Mechanism for decarboxylation of β-ketoacids
OH(R') OH(R') OH(R') R R R O OH O H O C O O O 18 REACTIONS OF CARBOXYLIC ACIDS
acyl chloride
anhydride
ester
19 DERIVATIVES: PHYSICAL PROPERTIES
• Because all carbonyl compounds have a polar carbonyl group, they exhibit dipole-dipole interactions.
• Because they contain one or two N—H bonds, 1° and 2° amides are capable of intermolecular hydrogen bonding.
20 DERIVATIVES: PHYSICAL PROPERTIES
O C MW = 60 bp 118 °C H3C OH
21 REACTION OF CARBOXYLIC ACID DERIVATIVES: NUCLEOPHILIC ACYL SUBSTITUTION
22 DERIVATIVES: STRUCTURE AND BONDING
• Three resonance structures stabilize carboxylic acid derivatives (RCOZ) by delocalizing electron density.
stability reactivity
23 INTRODUCTION TO NUCLEOPHILIC ACYL SUBSTITUTION
All derivatives are hydrolysed to carboxylic 24 acids ACID CHLORIDES: NOMENCLATURE
25 ACID CHLORIDES: SYNTHESIS
By the reaction of a carboxylic acid with thionyl chloride (SOCl2).
26 ACID CHLORIDES: REACTIONS • Acyl chlorides are the most reactive among carboxylic acid derivatives • A weak, non nucleophilic, base like pyridine is often added to the reaction mixture to remove the byproduct HCl.
anhydride
ester
(acid chlorides are readily acid decomposed by water)
amide 27 ANYDRIDES: NOMENCLATURE
acetic benzoic acetic benzoic anhydride anhydride anhydride
succinic maleic phthalic anhydride anhydride anhydride
succinic maleic phthalic acid acid acid 28 ANHYDRIDES: SYNTHESIS
1. By dehydration of carboxylic acids at high temperatures (700-800 °C) and/or in the presence of condensing agents
Formation of cyclic anhydrides is easier
2. From an acid and an acyl chloride
29 ANHYDRIDES: REACTIONS
• Anhydrides are strong acylating agents • A weak acid is formed as by-product.
ester
(anhydrides are readily acid decomposed by water)
amide
30 REACTIONS OF ANHYDRIDES
Anhydrides are very common acylating agents for the synthesis of esters and amides:
31 ESTERS: NOMENCLATURE
Esters are the (formal) condensation products of an acid and an alcohol
Lactones are cyclic esters
Butyrolactone 4-hydroxybutanoic acid Valerolactone 5-hydroxypentanoic (valeric) acid (a γ-lactone) (a γ-hydroxyacid) (a δ-lactone) (a δ-hydroxyacid) 32 INTERESTING ESTERS
Many low molecular weight esters have pleasant and very characteristic odors.
33 ESTERS: SYNTHESIS
34 ESTERS FROM CARBOXYLIC ACIDS
• SN2 (mainly for methyl esters).
• Fischer esterification.
35 FISCHER ESTERIFICATION
The reaction is an equilibrium, so it is driven to the right by using excess alcohol or by removing water as it is formed.
36 ESTERS: REACTIONS
Acid hydrolysis
37 ESTERS: REACTIONS • Basic hydrolysis of an ester is also called saponification.
• Hydrolysis is base promoted, not base catalyzed, because the base (OH–) is the nucleophile that adds to the ester and forms part of the product. It participates in the reaction and is not regenerated later.
38 LIPID HYDROLYSIS
Soap is prepared by the basic hydrolysis or saponification of a triacylglycerol. Heating an animal fat or vegetable oil with aqueous base hydrolyzes the three esters to form glycerol and sodium salts of three fatty acids. These carboxylate salts are soaps.
39 SOAP • Soap molecules self-aggregate in water to form micelles
Micelles are water-soluble because the heads are hydrophilic. Fats and oils from dirt dissolve in the hydorphobic core and are taken into solution
• Synthetic detergents O O Na+ sodium laurylsulfate S SDS O O- cetyltrimethylammonium + - bromide N Br CTAB
40 ESTERS: OTHER REACTIONS
acid H+, H2O or OH-
transesterification H+, ROH or RO-
amide
Mechanism of amide formation
41 AMIDES: STRUCTURE
42 AMIDES: STRUCTURE H H H + δ+ Amide resonance N N N O O- Oδ-
C, N, O: sp2 O planar restricted rotation H N
H R' R N R N Trans amides are more R' H stable than cis amides O O N-METHYLACETAMIDE • The rotational barrier is unusually high in amides (15-20 kcal/mol) due to the partial double bond character of the C-N bond. • Trans-amides are more stable than cis-amides.
16,0
12,0
8,0 E (kcal/mol)
4,0 15 kcal/mol cis
trans 2 kcal/mol 0,0 trans 180 150 120 90 60 30 0 -30 -60 -90 -120 -150 -180 O-C-N-H Dihedral angle AMIDES: BASICITY
pKa = 9
pKa = -1 AMIDES: NOMENCLATURE All 1° amides are named by replacing the -ic acid, -oic acid, or -ylic acid ending with the suffix amide.
2° and 3° amides are named as N-substituted (2°) or N,N- disubstituted (3°) derivatives of 1° amides
derived from butanoic acid
N-cyclohexyl-N-methylbutanamide 46 SYNTHESIS OF AMIDES
47 AMIDES FROM CARBOXYLIC ACIDS
Carboxylic acids cannot be converted into amides by reaction with
NH3 or an amine.
Carboxylic acids are converted into amides by reaction with NH3 or an amine in the presence of a condensing agent (DCC).
48 REACTIONS OF CARBOXYLIC ACIDS: AMIDES
49 AMIDES: REACTIONS
Amides are the least reactive of the carboxylic acid derivatives.
50 AMIDES: REACTIONS The mechanism of amide hydrolysis is exactly the same as the mechanism of ester hydrolysis.
Amide hydrolysis is hard in acid because the nucleophile (H2O) and the electrophile (amide) are poor. Amide hydrolysis is hard in base because the electrophile - and the leaving group (NR2 ) are poor. 51 SUMMARY OF NUCLEOPHILIC ACYL SUBSTITUTIONS
52 REDUCTION: ACID CHLORIDES, ANHYDRIDES AND ESTERS
Acid chlorides, anhydrides and esters are reduced to 1ry alcohols by Al hydrides, e.g. LiAlH4 A two-step reaction:
1. Nucleophilic acyl substitution
Z = Cl, OCOR, OR’
53 REDUCTION OF ACID CHLORIDES, ANHYDRIDES AND ESTERS
• LiAlH4 is a strong reducing agent that reduces acids, acid chlorides, anhydrides and esters to primary alcohols.
• Diisobutylaluminum hydride ([(CH3)2CHCH2]2AlH, abbreviated DIBAL-H, has two bulky isobutyl groups which makes this
reagent less reactive than LiAlH4. • DIBAL-H reduces acid chlorides, anhydrides and esters to aldehydes.
DIBAL-H
54 REDUCTION OF ACID CHLORIDES, ANHYDRIDES AND ESTERS
55 REDUCTION OF CARBOXYLIC ACIDS AND THEIR DERIVATIVES
56 SELECTIVE REDUCTION OF CARBONYL COMPOUNDS
57 REDUCTION OF AMIDES
• Amides are reduced to amines by Al hydrides, e.g. LiAlH4 • A two-step reaction:
Nucleophilic addition-elimination
imminium ion
Nucleophilic addition
58 REDUCTION OF AMIDES
59 REACTION OF ORGANOMETALLIC REAGENTS WITH CARBOXYLIC ACID DERIVATIVES.
• Both esters and acid chlorides form 3° alcohols when treated with two equivalents of either Grignard or organolithium reagents. • A two-step reaction:
1. Nucleophilic acyl substitution
2. Nucleophilic addition
60 REACTION OF ORGANOMETALLIC REAGENTS WITH CARBOXYLIC ACID DERIVATIVES.
• Organocuprates (R’2CuLi) are less reactive than organolithium and organomagnesium compounds.
• R’2CuLi react only with acid chlorides, which are the more reactive among carboxylic acid derivatives, to give a ketone as the product.
• Esters do not react with R’2CuLi.
61 REACTION OF ORGANOMETALLIC REAGENTS WITH CARBOXYLIC ACID DERIVATIVES.
62 SUMMARY: IMPORTANT REACTIONS OF ACID CHLORIDES.
63 SUMMARY: IMPORTANT REACTIONS OF ANHYDRIDES.
64 SUMMARY: IMPORTANT REACTIONS OF ESTERS.
65 SUMMARY: IMPORTANT REACTIONS OF AMIDES.
66 NATURAL AND SYNTHETIC FIBERS
• Fibers like wool and silk are proteins obtained from animals. • Cotton and linen are derived from carbohydrates having the general structure of cellulose.
67 NATURAL AND SYNTHETIC FIBERS: NYLON—A POLYAMIDE
Nylon 6 H O H O N N N N H O H O monomers: or
6-aminohexanoic acid ε-caprolactam
NH2 HOOC monomers: H2N COOH hexamethylenediamine adipic acid 68 NATURAL AND SYNTHETIC FIBERS: NYLON—A POLYAMIDE
• Nylon is a condensation polymer
69 NATURAL AND SYNTHETIC FIBERS: POLYESTERS
70 NITRILES
• Nitriles are not common in nature.
• Cyanohydrins are the most common natural nitriles.
71 NOMENCLATURE — NITRILES
72 NITRILES
• Nitriles are prepared by SN2 reactions of unhindered methyl and 1° alkyl halides with ¯CN.
• Nitriles are prepared by dehydration of amides (more general).
73 ACID CHLORIDES: SYNTHESIS
By the reaction of a carboxylic acid with thionyl chloride (SOCl2).
74 REACTIONS OF NITRILES – NUCLEOPHILIC ADDITION TO THE CN GROUP
- - Nu: = H ([Al]-H); R (R-[M]); H2O
75 SUMMARY: IMPORTANT REACTIONS OF NITRILES.
76 REACTIONS OF NITRILES — REDUCTION
LiAlH4 (more reactive)
77 REACTIONS OF NITRILES — REDUCTION
DIBAL-H (less reactive)
78 ADDITION OF ORGANOMETALLIC REAGENTS
Both Grignard and organolithium reagents react with nitriles to form ketones with a new C—C bond.
79 ADDITION OF ORGANOMETALLIC REAGENTS
80 REACTIONS OF NITRILES—HYDROLYSIS
81 REACTIONS OF NITRILES — HYDROLYSIS
82