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Preparation and Reactions of
Carboxylic Acids
Learning Objectives
1- Synthesis (preparation) of carboxylic acids by:
1.1 Oxidation of primary alcohol
1.2 Carboxylation of Grignard reagents
1.3 Hydrolysis of Nitriles
2-Reactions of carboxylic acids:
2.1 Neutralization
2.2 Reduction
2.3 Alkylation
2.4 Decarboxylation of β-dicarboxylic acids
Acid base definitions
First Theory : Brønsted–Lowry acid–base theory
Acid
Base
It donates hydrogen ions (H+) It accepts hydrogen ions (H+)
such as HCl, HNO3
such as NH3, CH3COO-, OHCH3COOH
Acid + Base
HA + B
CH3COOH + H2O
conjugate base + conjugate acid
ACH3COO-
+
BA+
+
H3O +
Second theory: Lewis definitions
Acid
Base
 Lewis acid : electron pair
Acceptor
 Lewis Acids are Electrophilic
 Lewis Base: Lone pair Donor
 Lewis Bases are Nucleophilic
Examples
1. All cations are Lewis acids since
they are able to accept electrons. (e.g.,
Cu2+, Fe2+ )
2. An atom, ion, or molecule with an
incomplete octet of electrons can
act as an Lewis acid (e.g., BF3,
AlF3).
3. Molecules that have multiple bonds
between two atoms of different
electronegativities (e.g., CO2, SO2)
Examples of lewis base are
electron pair donors which include
1. simple anions, such as OH-, CN, RCOO- and F2. lone-pair containing species,
such as H2O, NH3, CO
3. electron rich π-system Lewis
bases, such as pyridine and
benzene
Electrophile (El)
Nucleophile (Nu)
-Electron deficient group
accepting an electron pair
-It can be neutral or positively
charged
- It has affinity to bond to a Lewis
base or a nucleophile
Because electrophiles accept
electrons, they are Lewis acids
Examples :
1. Cations such as H+ and NO+
2. Neutral molecules such as HCl,
Cl2 and Br2,
3. Carbon in alkyl halides, acyl
halides, and carbonyl
compounds
( e.g keton and ester)
1. Carbon electrophiles in alkyls
-Electron rich group donating an electron pair
- It can be neutral or negatively charged
-It attacks the + charge on electrophile, or bonds
to a Lewis acid
Because nucleophiles donate electrons, they are
by definition Lewis bases
Examples
1. Anions, such as Cl-, CN-, and F2. lone-pair containing species, such as NH3
3. Carbon nucleophiles in the Grignard reagent
(CH3 – MgBr) and organolithium reagent
(CH3 – Li).
4. Oxygen nucleophiles are H2O, OH-, RCOO−,
5. Sulfur nucleophiles: H2S,RSH, RS6. Nitrogen nucleophiles include ammonia,
azide N3-, amines, and nitrites.
Common electrophiles and nucleophiles
Chemical group
proton (H3O+)
alkyl halide (CH3-Br)
alcohol (CH3-OH)
aldehyde (CH3 - CHO)
ketone (CH3 - CO - CH3)
acid chloride (CH3 - CO - Cl)
Type
electrophile
electrophile
electrophile
electrophile
electrophile
electrophile
ester (CH3 - CO - OCH3)
boron trifluoride (BF3)
thionyl chloride (Cl - SO - Cl)
phosphorous trichloride (PCl3)
chloride ion (Cl-)
hydroxide ion (OH-)
methoxide ion (CH3O-)
cyanide (CN-)
Organolithium compound (CH3 - Li)
Grignard reagent (CH3 - MgBr)
amine (N(CH3)3)
phosphine (P(CH3)3)
pi bond (H2C = CH2)
electrophile
electrophile
electrophile
electrophile
nucleophile
nucleophile
nucleophile
nucleophile
nucleophile
nucleophile
nucleophile
nucleophile
nucleophile
Example : Decide if each molecule or ion shown below will react
as a nucleophile or electrophile, or both.
Solution :
a. Bromide ion: This atom has four lone pairs and a formal negative
charge, suggesting it is electron-rich and can therefore function as a
nucleophile. If it has none of the features that would suggest it might
behave as an electrophile.
b. Ammonium ion: This ion has a formal positive charge, suggesting it is
electron-poor and can therefore function as an electrophile. It has no lone
pairs or negative charge, suggesting it will not function as a nucleophile.
c. Water: The oxygen atom of water has two lone pairs and a δ - charge
(oxygen is more electronegative than hydrogen). This suggests that water
can behave an a nucleophile. Each hydrogen atom bears a δ + charge, so
the molecule can behave as an electrophile as well.
Many molecules can be both nucleophiles and electrophiles. How they
behave depends upon what they react with. For example, if water is
reacted with an electrophile, the water will behave as a nucleophile.
Examples of electrophile-electrophile reactions
Leaving Group LG
It is a group that tends- or favours -to leave with a pair of electrons
It can be neutral ( e.g NH3 & H2O) or anions ( OH-, halides)
What makes a Good Leaving Group ( LG)?
As for acidity, the more stable A- is, the more the
equilibrium will favour dissociation, and release of
H meaning that HA is more acidic.
For the leaving group, the more stable LG- is, the
more it favours "leaving“, meaning that the better
leaving group LG- is .
Examples of Leaving groups
Synthesis of Carboxylic acids
(1) oxidation of 1o alcohols
• Carboxylic acids can be prepared by oxidizing primary
alcohols or aldehydes. The oxidation of primary
alcohols leads to the formation of aldehydes that
undergo further oxidation to yield acids.
• The oxidation of ethanol produces ethanoic acid (acetic
acid).
OH
|
CH3—CH2
O
[O]
||
[O]
CH3—C—H
ethanol
(ethyl alcohol)
ethanal
(acetaldehyde)
O
||
CH3—C—OH
ethanoic acid
(acetic acid)
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(1) oxidation of 1o alcohols
All strong oxidizing agents (potassium permanganate
KMnO4 , potassium dichromate K2Cr2O7, and chromium
trioxide CrO₃) can easily oxidize the aldehydes that are
formed.
CH3CH2CH2CH2-OH + CrO3  CH3CH2CH2COOH
n-butyl alcohol
butyric acid
1-butanol
butanoic acid
CH3
CH3CHCH2-OH + KMnO4 
isobutyl alcohol
2-methyl-1-propanol`
CH3
CH3CHCOOH
isobutyric acid
2-methylpropanoic acid
(2) Carboxylation of Grignard Reagents
Grignard reagents are strong nucleophiles reacting with electrophiles
such as carbonyl compound
Grignard Reagents Increase the carbon chain by one carbon.
Grignard reagents are also very strong bases and will react with acidic
hydrogens (such as alcohols, water, and carboxylic acids).
Grignard reagents react with carbon dioxide to yield acid salts, which,
upon acidification, produce carboxylic acids.
hydrolysis
Gringard reagent
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NUCLEOPHILIC ADDITION OF RMgX
TO CARBON DIOXIDE
( carbon in Gringard reagent is partly negative and magnesium is partly
positive because the C is more elctronegative than Mg)
Step 1:
The nucleophilic C in the Grignard reagent adds to
the electrophilic C in the polar carbonyl group,
electrons from the C=O move to the
electronegative O creating an intermediate
magnesium carboxylate complex.
Step 2:
Protonation of the carboxylate oxygen creates the
carboxylic acid product from the intermediate
complex.
(3) Hydrolysis of Nitriles
Nitriles are compounds which contain cyanide ion CN- attached to
a hydrocarbon group (R).
Cyanide ion is an excellent nucleophile and will react with alkyl
halides to give nitriles. This reaction involves 2 steps and results in
an increase in the length of the carbon chain because of the extra
carbon in the -CN group. The nitrile can be hydrolyzed to a
carboxylic acid
General Example
nitrile
hydrolysis
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Step 1. Nitriles are prepared by SN2 (Nucleophilic
substitution ) reactions of alkyl halids ( R-X) with Sodium
cyanide NaCN
Step 2. Hydrolysis of the nitriles yields a carboxylic acids
(-C≡N is converted to –COOH)
Specific Examples
1.
2.
CH3-Br
CH3-CN
CH3COOH + NH4+
Learning Check
What alcohol could be used to prepare the
following:
1. butanoic acid
2. propanoic acid
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Solution
What alcohol could be used to prepare
the following:
[O]
1. butanol
[O]
butanal
[O]
2. propanol
acid
butanoic acid
[O]
propanal
propanoic
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Reactions of Carboxylic Acids
1.Neutralization
Salts of Carboxylic Acids
 Carboxylic acids are neutralized by strong bases to
give carboxylate salts.
 as long as the molecular weight of the acid is not too
high, sodium and potassium carboxylate salts are
soluble in water
1.Neutralization
O
RCOH
O
+
HO–
RCO–
+
H2O
weaker
acid
stronger
acid
salt
Fatty Acids; Carboxylic Acids (R-CO2H) where R
group contains 12-18 carbons.
Soaps/detergents; Salts of long chain fatty acids
Micelles: substances with polar (hydrophilic) head groups and
hydrophobic tail groups form aggregates in water with the
carboxylate groups on the outside and nonpolar tails on the inside.
Steric acid
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Micelles
O
O
CH3(CH2)16C OH + NaOH
nonpolar
–
CH3(CH2)16CO Na+ + H2O
polar
2.Reduction
Reduction to a 1° alcohol
Use strong reducing reagent: LiAlH4.
It reduces carboxylic acid to alcohol.
Reduction to Aldehyde
• Difficult to stop reduction at aldehyde.
• Use a more reactive form of the acid
(an acid chloride) and a weaker reducing
agent, lithium aluminum
tri(tbutoxy)hydride.
benzaldehyde
3.Alkylation to Form Ketones
React 2 equivalents of an organolithium reagent
(e.g CH3-Li) with a carboxylic acid to produce
keton.
CH2CH3
Benzoic acid
Ethyl phenyl ketone
4. Decarboxylation
Decarboxylation: is loss of carbon dioxide, Reaction type: Elimination
Simple carboxylic acids do not decarboxylate readily
O
RCOH
RH + CO2
most carboxylic acids, if heated to a very high temperature, undergo
thermal decarboxylation
most carboxylic acids, however, are quite resistant to moderate heat and
melt or even boil without decarboxylation
4. Decarboxylation
Carboxylic acids with a carbonyl group at the 3- (or β-) position
readily undergo thermal decarboxylation, e.g. derivatives of
malonic acid.
The reaction proceeds via a cyclic transition state giving an enol
intermediate that tautomerizes to the carbonyl
O
O
HOCCH2COH
150°C
O
CH3COH +
CO2
4. Decarboxylation
Step 1:
Remember curly arrows flow.... Start at the
protonation of the carbonyl, break the O-H
bond and form the p bond, break the C-C
and make the C=C. Note the concerted
nature of this reaction and the cyclic
transition state.
Step 2:
Tautomerization of the enol of the
carboxylic acid leads to the acid product
(not shown here).