164 Organic Chemistry II (Chem 2042)

Unit 4. Oxidation–Reduction reactions

Contents
4.1. Oxidation Reactions
4.1.1. Alcohols
4.1.2. Aldehydes
4.1.3. Multiple Bonds
4.2. Reduction Reaction
4.2.1. Catalytic Hydrogenation
4.2.2. Dissolving metal reduction
4.2.3. Hydride Reduction
4.3. Summary
4.4. Exercise

Learning outcome

 identify the species that have undergone oxidation and those that have undergone
reduction.
 know the oxidation states of different compounds
 Study chemistry of different oxidizing reagents
 choose appropriate reagent for selective oxidation.
 understand the chemistry of different reducing reagents.
 select appropriate reagent for selective reduction.

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Oxidation–Reduction reactions
The reaction involving the transfer of electrons from one molecule to another are called
oxidation-reduction reactions or redox reactions. These reactions are used in the synthesis
of a large variety of compounds and are known in biological systems as well. In an oxidation-
reduction reaction, one compound is oxidized by losing electrons while the other compound
is reduced by gaining electrons. Oxidation and reduction both undergo simultaneously in a
reaction; a compound cannot gain electrons (be reduced) unless another compound in the
reaction simultaneously loses electrons (is oxidized). The compound that is oxidized is called
the reducing agent because it transfers electrons to the other compound to reduce it.
Similarly, the compound that is reduced is called the oxidizing agent because it gains the
electrons given up by the other compound when it is oxidized.
However, most organic compounds are uncharged, and gain or loss of electrons is not
obvious. In an organic reaction, the oxidation and reduction of a compound is determined by
the replacement of hydrogen atom with an electronegative atom (O, N, halogen) or vice
versa. Thus, a compound is reduced, if the reaction increases the number of CH bonds or
decreases the number of CO, CN or CX (a halogen) bonds. A compound is oxidized if
the reaction decreases the CH bonds or increases the number of CO, CN or CX (a
halogen) bonds. For example:

The total number of CO, CN or CX (a halogen) bonds of a carbon is called the oxidation
state of that carbon.

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In the organic reactions, several oxidizing and reducing agents are used for the transformation
of one functional group to another functional group. Some oxidizing and reducing agents are
very selective to oxidize or reduce one functional group and not the other. Such type of
oxidizing and reducing agents are very helpful in getting desirable results if the reactants
contain more than one functional group.
4.1. Oxidation Reactions
As described earlier, the oxidation at carbon decreases the number of CH bond or
increases the number of CO, CN or CX bonds. The oxidation is carried out with
oxidizing agents which are grouped into two categories:
a) Reagents that contain oxygen-oxygen bonds – These reagents include O2
(oxygen), O3 (ozone), H2O2 (hydrogen peroxide), (CH3)3COOH (tert-butyl
hydroperoxide), and peracids. They all contain a weak OO bond which is
cleaved during oxidation.
b) Reagents that contain metal-oxygen bonds – These reagents mostly contain
either chromium in +6 oxidation state (six CrO bonds) or manganese in +7
oxidation state (seven MnO bonds). For example, CrO3 (chromium oxide),
K2Cr2O7 (potassium dichromate), Na2Cr2O7 (sodium dichromate), KMnO4
(potassium permanganate). These reagents are used in presence of strong
aqueous acids like H2SO4. Other oxidizing agents are OsO4 (osmium
tetraoxide) and Ag2O (Silver oxide). Pyridinium chlorochromate (PCC) is
soluble in halogenated organic solvents and can be used without strong acid
present. This is a mild oxidizing agent, and thus is more selective oxidant.
4.1.1. Oxidation of Alcohols
Oxidation of an alcohol results in the formation of an aldehyde, a ketone, or a
carboxylic acid depending on the alcohol and on the oxidizing agent.

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 Depending on the oxidizing agent used in the reaction, primary alcohols are
oxidized to aldehydes or carboxylic acids by replacing either one or two CH
bonds by CO bonds.

 Secondary alcohols on oxidation yield ketones by replacing one CH bond by

CO bond.

 Tertiary alcohols contain no H atoms on the carbon with the OH group, so they
don’t react with most of the oxidizing agents.

Different oxidizing agents are used to oxidize alcohols based on the product desired.
The oxidation of primary alcohols with strong oxidizing agents results in the
formation of aldehydes which is further oxidized to carboxylic acids while mild
oxidizing agents produce aldehydes.
Oxidation by strong oxidizing agents:
Chromic acid (H2CrO4) is generally used to oxidize primary alcohols to carboxylic
acids, and secondary alcohols to ketones. Chromic acid is prepared by dissolving
either chromium trioxide (CrO3) or sodium (or potassium) dichromate in aqueous
H2SO4.

A solution of chromic acid in aqueous sulfuric acid is known as the Jones

reagent.Because most of the organic compounds are insoluble (or slightly soluble) in

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water, they are first dissolved in acetone and then Jones reagent is added to complete
the oxidation.Acidified KMnO4 is also used to oxidize alcohols.
Primary alcohols are initially oxidized to aldehydes by these reagents. The reaction,
however, does not stop at the aldehyde. Instead, the aldehyde is further oxidized to a
carboxylic acid. Secondary alcohols are oxidized to ketones which do not oxidize
further because ketones don’t have any CH bond to be converted to CO bond.
O O
CrO3/H2SO4 or further
CH3CH2CH2OH CH3CH2CH CH3CH2COH
Na2Cr2O7/H2SO4 or oxidation
a primary alcohol an aldehyde a carboxylic acid
KMNO4/H2SO4

OH O
CrO3/H2SO4 or
CH3CH2CHCH3 CH3CH2CCH3 no further oxidation
Na2Cr2O7/H2SO4 or
a secondary alcohol a ketone
KMNO4/H2SO4
However, ketones are cleaved t carbonyl carbon on either side to give carboxylic acid
in presence of strong oxidizing agents such as conc. HNO3.
O conc. HNO3
O O
R C R' R C OH + HO C R'

Mechanism:
Oxidation of secondary alcolol:
Step 1 and 2: Formation of chromate ester. Nucleophilic attack of the alcohol on
the electrophilic metal followed by proton transfer forms a chromate ester. No
oxidation takes place in these steps.

Step 3: Elimination of the chromate ester and oxidation of the carbinol carbon
(formation of ketone).A base (H2O or alkoxide of the starting alcohol) removes a
proton, with the electron pair in the CH bond forming the new π bond of the CO.
Oxidation at carbon occurs in this step because the number of CH bonds decreases
and the number of CO bonds increases.

Oxidation of primary alcohol:

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Oxidation of primary alcohol undergoes in two parts – oxidation to aldehyde and then
further oxidation of aldehydes to carboxylic acid.
Part 1: Oxidation to aldehydes. The mechanism of oxidation of primary alcohol to
aldehyde is same as described in the oxidation of secondary alcohol to ketone.
Part 2: Oxidation of aldehydes to carboxylic acid. Aldehyde itself is not oxidized
by chromic acid, because chromic acid can only react with an –OH, not with
carbonyl. Therefore, aldehyde is first converted to its hydrate by the addition of a
molecule of water to the aldehyde carbonyl group. Then, an –OH of the aldehyde
hydrate reacts with chromic acid to complete the oxidation of the aldehydes to
carboxylic acids.

Mild oxidizing agents:

Pyridinium chlorochromate (PCC): The oxidation of a primary alcohol can be easily
stopped at the aldehyde if pyridinium chlorochromate (PCC) or pyridinium
dichromate (PDC) (C6H5NH)22+Cr2O72- are used as the oxidizing agents. PCC, also
known as Corey’s reagent, is a complex of chromium trioxide with pyridine and
HCl, and oxidizes most primary alcohols to aldehydes in excellent yields.

Unlike most other oxidants, PCC and PDC are soluble in nonpolar solvents such as
dichloromethane (CH2Cl2), which is an excellent solvent for most organic
compounds. Moreover, as the reaction undergoes in absence of water, the product
aldehyde is not converted to aldehyde hydrate; therefore, further oxidation of
aldehyde to carboxylic acid is stopped.
PCC and PDC are not only selective for the oxidation of primary alcohols to
aldehydes but also do not affect carbon-carbon double bonds or other easily oxidized
functional groups. For example,

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Secondary alcohols are also oxidized by PCC or PDC to ketone.

Swern Oxidation:

Because of the toxicity of chromium-based reagents discussed above, other methods

like Swern oxidation is widely in practice for the oxidation of alcohols, which uses
dimethyl sulfoxide (DMSO) as the oxidizing agent to convert primary alcohols to
aldehydes and secondary alcohols to ketones. DMSO and oxalyl chloride are added to
the alcohol at low temperature, followed by a hindered base such as triethylamine.
The actual reactive species (CH3)2S+Cl (dimethylchlorosulfonium ion), formed in the
solution from the reaction of dimethyl sulfoxide and oxalyl chloride, is the oxidizing
agent in the Swern oxidation.

Since the reaction is not carried out in an aqueous solution, the oxidation of a primary
alcohol (like PCC oxidation) stops at the aldehyde. Secondary alcohols are oxidized to
ketones. The by-products of this reaction are all volatile and are easily separated from
the organic products.

Mechanism:
Like chromic acid oxidation, the Swern oxidation uses an E2 reaction to form the
aldehyde or ketone.

Oxidation of Glycols (vicinal diols):

Glycols, on oxidation with periodic acid, HIO4 or lead tetraacetate, Pb(OCOCH3)4
result in the formation of acid and/or ketone depending upon the substitution. In the
process, periodic acid is reduced to iodic acid.

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In case of small-ring cyclic glycols, cis-isomer oxidizes faster than the trans-isomer;
for example, cis-cyclohexan-1, 2-diol is oxidized to dialdehyde while trans-isomer
remains unchanged.
4.1.2. Oxidation of Aldehydes
Aldehydes are oxidized much more readily; therefore, in addition to chromic acid (a
strong oxidizing agent), potassium permanganate, and potassium dichromate
oxidation, as discussed above, aldehydes undergo oxidation even with mild oxidizing
reagents, e.g. Tollens reagent, Fehling’s solution, and Benedict’s reagent. Ketones do
not get oxidized by these reagents; hence these reagents are used to distinguish
aldehydes and ketones.
Tollens reagent: Tollens reagent is an ammonical silver nitrate solution. Tollens
reagent on heating with aldehydes forms a black suspension with shiny silver mirror
deposited on the side of the test tube; silver ion (Ag+ in silver nitrate) oxidizes
aldehydes to carboxylic acids and itself gets reduced to metallic silver. Hence the
reaction is called silver mirror test.
O O
H2O
R C H + 2Ag(NH3)2 +
-
3OH 2Ag + R C O- + 4NH3 + 2H2O
aldehyde Tollens reagent silver carboxylate

Simple hydrocarbons, ethers, ketones and even alcohols do not react with the Tollens
reagent. The reaction is used industrially to produce shiny silver mirror on glass
surfaces, such as the inside of Thermos flasks.
Fehling’s solution: The Fehling’s solution is a mixture of two solutions – Fehling’s
solution A (alkaline CuSO4) and Fehling’s solution B (sodium potassium tartarate in
sodium hydroxide). The two solutions are mixed in equal amounts which results in the
formation of deep blue coloured copper tartarate complex furnishing cupric (Cu++)
ions. The cupric ion on heating with aldehydes is reduced to cuprous oxide giving a
red precipitate, and the aldehydes are oxidized to carboxylic acids.
O O
H2O
R C H + 2Cu ++
+ 5OH - Cu2O + R C O- + 3H2O
aldehyde red ppt. carboxylate
Benedict solution: An alkaline solution of copper sulfate, sodium acetate, and sodium
carbonate is called Benedict solution. The reaction of aldehydes with Benedict
solution is same as with Fehling’s solution. Like Fehling’s solution, it furnishes
cupric ion which oxidizes aldehydes to carboxylic acid and itself get reduced to form
red precipitate of cuprous oxide.

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Baeyer-Villiger oxidation:
Ketones do not react with most of the reagents used to oxidize aldehydes. However,
both aldehydes and ketones can be oxidized by a peroxyacid. Aldehydes are oxidized
to carboxylic acids and ketones are oxidized to esters. An oxygen atom is inserted
between the carbonyl carbon and the H of an aldehydes or the R of a ketone.
O O O O
+ +
C C C C
R H R' OOH R OH R' OH
aldehyde peroxyacid carboxylic acid

O O O O
+ +
C C C C
R CH3 R' OOH R OCH3 R' OH
ketone peroxyacid ester
A cyclic ketone undergoes Baeyer-Villiger rearrangement to form a cyclic ester called
lactone.

Mechanism:
The nucleophilic addition of peroxyacid to carbonyl carbon results in the formation of
unstable tetrahedral intermediate with a very weak OO bond. This step is analogous
to the formation of hemiacetal. The weak OO bond breaks with the 1, 2-shift of H of
aldehydes or alkyl group of ketone to form carboxylic acid or ester, respectively.

When the two alkyl groups attached to the carbonyl group of the ketone are different,
the migration of the alkyl group occurs in the following order:
CH3< 1o alkyl < 2o alkyl ~ phenyl < cyclohexyl < 3o alkyl < H
For example:
Baeyer-Villiger oxidation of cyclohexyl methyl ketone results in the formation of
cyclohexyl acetate, not methyl cyclohexanecarboxylate because cyclohexyl group is
more likely to migrate than a methyl group.

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Aldehydes are always oxidized to carboxylic acids, since H has the greatest tendency
to migrate.

4.1.3. Oxidation of Multiple Bonds

Compounds having multiple bonds like alkenes and alkynes are oxidized to produce
different compounds depending on the type of oxidizing reagent as well as on the
reaction conditions.
With cold alkaline KMnO4 (Baeyer’s reagent):
The aqueous alkaline solution of potassium permanganate oxidizes alkenes and results
to the formation of cis-diols; hydroxylation occurs at the double bond position. The
permanganate adds to the alkene double bond to form a cyclic ester which is
hydrolyzed by the base to form diol.
H2C CH2 H2O H2C CH2
H2C CH2 + MnO4-
O -MnO2 OH OH
Ethene O
Mn Ethane-1,2-diol
O O
cis-addition
A similar reaction occurs with alkynes. An alkyne on treatment with cold, aqueous
potassium permanganate under nearly neutral conditions oxidized to a -diketone.
This is conceptually the same as hydroxylating each of the two pi bonds of the alkyne,
then losing two molecules of water to give the diketone.

The reaction is known as Baeyer’s test is used to test unsaturation. KMnO4 solution is
purple in colour and after reacting with unsaturated compounds (alkene or alkyne)
produce colourless diols; the decolourization of purple KMnO4 solution indicates the
presence of unsaturation.
With osmium tetroxide (OsO4):
Reaction of alkene with osmium tetroxide is same as with potassium permanganate;
alkene reacts with OsO4 to form an osmate ester which on hydrolysis produces cis-
diols.

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H2C CH2 H2O H2C CH2

H2C CH2 + OsO4
O O NaHSO3 OH OH
Ethene
Os Ethane-1,2-diol
O O
cis-addition
Oxidative cleavage with acidified or hot KMnO4 or acidified K2Cr2O7:
A cold aqueous KMnO4 solution oxidizes an alkene to a cis-diol. However, acidified
or hot KMnO4 solution is much stronger oxidizing agent and oxidizes diol further to
give carboxylic acid or ketones through the cleavage of CC double bond. The
terminal =CH2 group is oxidized completely to produce CO2 and H2O. Acidified
K2Cr2O7 or Na2Cr2O7 also give the same reaction.
O O
KMnO4 /H+
CH3CH CH2 CH3C OH + HC OH
or hot KMnO4
or K2Cr2O7/ H+ [O]
CO2 + H2O

Olefinic carbon with no hydrogen attached to it gets oxidized only upto ketones,
which are very difficult to oxidize further to carboxylic acids.
KMnO4 /H+
CH3C CHCH3 CH3C O + CH3C OH
or hot KMnO4
CH3 or K2Cr2O7/ H+ CH3 O
ketone carboxylic acid
With ozone:
Electrophilic addition of ozone to alkene produces a cyclic peroxide known as
ozonide; the reaction results in the cleavage of CC double bond. The ozonide being
explosive is not isolated; rather further decomposition of ozonide is carried out by
reduction (known as reductive ozonolysis) or by oxidation (called oxidative
ozonolysis).
 The reductive ozonolysis with Zn/H2O forms aldehydes and/or ketone;
aldehyde is formed if the sp2 carbon of the alkene contains atleast one
hydrogen atom, and ketone is formed if the sp2 carbon of the alkene is bonded
to two alkyl substituents.
 The oxidative ozonolysis with H2O2 produces carboxylic acid and /or ketones.
Carboxylic acids are formed instead of aldehydes because any aldehyde that is
initially formed will be immediately oxidized to a carboxylic acid by hydrogen
peroxide.

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R R
O3
C C
R H

The reaction of alkynes with ozone followed by hydrolysis results in the cleavage of
triple bond and forms two carboxylic acids. Unlike in alkenes, no oxidizing or
reducing agents are required here to react with ozonide; only hydrolysis is required.
The terminal alkyne group is oxidized to CO2.

Ozonolysis is used to determine the position of double or triple bond in a compound.

With peroxyacids:
The reaction of peroxyacids with alkene gives epoxide i.e. three-membered oxygen
containing ring. The reaction is called epoxidation and follows the electrophilic
addition mechanism. meta-Chloroperoxybenzoic acid (MCPBA), the magnesium salt
of monoperoxyphthalic acid (MMPP), and peroxyacetic acid are commonly used
peroxyacids.

Epoxidation of alkenes with peroxy acids is a syn addition to the double bond.
Substituents that are cis to each other in the alkene remain cis in the epoxide;
substituents that are trans in the alkene remain trans in the epoxide.
The reactivity of alkenes toward peroxycarboxylic acids increases with alkyl
substitution, allowing for selective oxidations. For example,

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4.2. Reduction Reaction

In general, gain of one or more electrons by an atom is called reduction. However, in
organic chemistry, reduction is defined as a gain of electron density by carbon, which
is achieved either by bond formation between carbon and a less electronegative atom
(usually hydrogen) or by bond-breaking between carbon and a more electronegative
atom (usually O, N, or a halogen). In other words, in reduction reactions, number of
CH bonds increases and/or number of CZ (where Z = O, N, or halogen) decreases.

During reduction hydrogen is added in three different forms to the compound to be

reduced corresponding three different mechanisms:

Catalytic hydrogenation Dissolving metal reduction Hydride reduction

4.2.1. Catalytic Hydrogenation (Reduction by addition of two

hydrogen atoms)
Catalytic hydrogenation is carried out by
passing hydrogen, in the presence of
catalyst to the unsaturated organic
compounds to yield corresponding reduced Without catalyst

products. The catalyst reduces the energy of

With catalyst
activation of the reaction and hence allows
the reaction to occur more rapidly. Without
catalyst, the reaction pathway has a very
high energy of activation and thus
undergoes too slow to be of practical use. A
number of metals are used as catalyst; the
most widely used metals are palladium, nickel, platinum, and nickel. Platinum and
palladium are used in finely divided state absorbed over charcoal (Pt/C or Pd/C) to

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maximize surface area. Platinum is also used in the form of oxide (PtO2) and is then
called as Adam’s catalyst. Nickel is generally used at a higher temperature (~300oC)
and the reaction is called Sabatier Senderens reaction.
Different compounds are catalytically reduced by using selective catalyst,
temperature, pressure, and solvent.
 Alkene and alkyne both are reduced to alkane by catalytic hydrogenation in
presence of Pd, Pt, or Ni.

The hydrogenation generally occurs with syn stereochemistry; both hydrogens

add to the double bond from the same face.

Partial hydrogenation of alkyne may be carried out by using specific

catalysts/reagents, which results in the formation of alkenes with specific
stereochemistry. For example, cis-alkene is formed if partially deactivated
Lindlar’s catalyst (Pd/CaCO3 in lead acetate poisoned with a small amount of
quinolone) is used in the reaction. Quinoline partially deactivates (“poison”) the
catalyst making it a poor catalyst for alkene hydrogenation while retaining its
ability to catalyze the addition of hydrogen to alkynes.

The hydrogenation of alkene or alkyne is exothermic reaction, and the energy

released in the reaction is called heat of hydrogenation. More heat of
hydrogenation of a compound means more easily it can be hydrogenated. The
more alkyl substituents bonded to sp2 carbons of an alkene, the greater is its
stability, and less is its heat of hydrogenation; means more substituted alkenes are
less reactive for hydrogenation. The order of reactivity of substituted alkenes
towards hydrogenation is:
Ethene > mono-substituted alkene >trans-alkene (di-substituted) >cis-alkene (di-
substituted) > tri-substituted alkene > tetra-substituted alkenes

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The heat of hydrogenation of an alkyne is greater than twice the heat of

hydrogenation of the derived alkene. Therefore, the first hydrogenation step of an
alkyne is more exothermic than the second.
 Carbon-nitrogen double and triple bonds can be reduced by catalytic
hydrogenation to yield amines:

 Catalytic hydrogenation of carbonyl compounds is mostly carried out in presence

of Raney nickel as a catalyst. Raney nickel is a finely divided hydrogen-bearing
form of nickel made by treating a nickel–aluminum alloy with a strong sodium
hydroxide solution. The aluminum in the alloy reacts to form hydrogen, leaving
behind a finely divided nickel powder saturated with hydrogen. As it already has
adsorbed hydrogen, so no external hydrogen is needed. Pt and Rh catalysts are
also used for hydrogenation of aldehydes and ketones. Aldehydes and acid
chlorides produce primary alcohols while ketones give secondary alcohols on
hydrogenation.

R
H2
C O R CH2OH
Raney Ni
Cl
acid chloride a primary alcohol
Catalytic reduction of aldehydes and ketones is simple to carry out, yields are
generally very high, and isolation of the final product is very easy. A
disadvantage is that some other functional groups are also reduced under these
conditions, for example, carbon-carbon double and triple bonds.

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The reduction of acid chloride can be stopped at an aldehyde by using partially

deactivated catalyst such as Pd catalyst supported over BaSO4 and poisoned with
little sulfur, which prevents further reduction of aldehyde to alcohol. The reaction
is known as Rosenmund reduction.

 The order of reactivity of different functional groups towards catalytic

hydrogenation is:
Acid chlorides > Alkyne > Aldehydes > Alkenes > Ketones > Nitriles > Imines
 Carboxylic acids, esters and amides are less reactive, and thus, cannot be reduced
by catalytic hydrogenation, except under extreme conditions.

Mechanism:
The process of hydrogenation is believed to begin with the interaction of hydrogen on
the surface of metal catalyst, effectively breaking the HH bonds and forming
individual hydrogen atoms adsorbed to the surface of the metal. Then -bond of the
alkene coordinates with the metal surface, and that allows the reaction between the -
bond of alkene and two hydrogen atoms. As the alkane, so formed, no longer has any
-bond to complex with the metal, it is released from the catalyst surface. In this
process two hydrogen atoms add to the same side of the alkene; that is called syn
addition.

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The reaction is extremely sensitive to the steric environment around the double bond.
The less hindered side of the alkene makes complex with the metal. For example, in
-pinene, the top side of the double bond is blocked by the methyl; therefore it
complexes with the metal from downside and thus the hydrogenation also takes place
exclusively from downside.

4.2.2. Dissolving metal reduction (Reduction by addition of an

electron, a proton, an electron and a proton)
Reduction of alkyne to trans-alkenes: As described in previous section that alkynes
are reduced to cis-alkenes by catalytic hydrogenation. Alkynes can be reduced to
trans-alkenes also by using sodium or lithium metal in liquid ammonia. The reaction
is called dissolving metal reduction.

Ammonia is a gas at room temperature (b.p. -33oC), so it is kept in the liquid state by
using dry ice/acetone mixture, and the reaction is carried out at low temperature.
When dissolved in liquid ammonia, sodium atom serves as a source of electrons and
ammonia provides proton:

The overall reaction adds two electrons and two protons to the compound.

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Mechanism:
Step 1: A single electron is transferred from the sodium atom to the alkyne,
generating a radical anion intermediate. One carbon of alkyne carries negative charge
while other contains an unpaired electron – thus called radical anion.

Step 2: The anion radical is a strong base and removes H+ from ammonia to give an
alkenyl radical.

Step 3: Another electron is transferred from the second sodium atom to the alkenyl
radical, generating trans-alkenyl anion because trans-isomer is more stable than cis-
isomer, and the stereochemistry of the final product is decided in this step.

Step 4: Alkenyl anion abstracts another proton from ammonia to give trans-alkene.

Dissolving metal reductions are stereoselective; they always form the more stable
trans product preferentially, because trans-isomer is more stable than cis-isomer.

Sodium (or lithium) in liquid ammonia cannot reduce a carbon–carbon double bond,
making it useful for reducing a triple bond in a compound that also contains a double
bond.

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Also it does not reduce terminal alkynes.

Birch reduction: Benzene and its derivatives can also be reduced to non-conjugated
cyclohexa-1,4-dienes by treatment with sodium or lithium in a mixture of liquid
ammonia and an alcohol.

These metal-ammonia-alcohol reductions of aromatic rings are called Birch

reductions. The Birch reduction not only provides a method to prepare dienes from
arenes, which cannot be accomplished by catalytic hydrogenation, but also gives a
non-conjugated diene system rather than the more stable conjugated one.

Mechanism:
Mechanism of Birch reduction is analogous to the mechanism of dissolving metal
reduction of alkyne. In this case the proton is provided by the alcohol instead of
ammonia.
Step 1: Transfer of an electron from sodium (the reducing agent) to the -system of
the aromatic ring produces an anion radical.

Step 2: Radical anion abstracts a proton from methanol to form cyclohexadienyl

radical.

Step 3: Transfer of another electron from sodium to cyclohexadienyl radical converts

it to cyclohexadienyl anion.

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Step 4: Transfer of another proton from methanol produces the final product 1,4-
cyclohexadiene.

Electron-withdrawing substituents stabilize the carbanions, while electron-donating

substituents destabilize them. Therefore, reduction takes place on carbon atoms
bearing electron-withdrawing substituents (such as those containing carbonyl groups)
and not on carbon atoms bearing electron-releasing substituents (such as alkyl or
alkoxy groups).

4.2.3. Hydride Reduction (Reduction by addition of a hydride ion and

a proton)
The third way of reducing a compound is the addition of hydride (H) and a proton
(H+). The most common hydride reducing agents contain hydrogen bonded to boron
or aluminum, for example, sodium borohydride (NaBH4) and lithium aluminum
hydride (LiAlH4). These reagents provide hydride (H) and thereby behave as a
nucleophile. Thereafter, a proton is added from the solvent (H2O or an alcohol).

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Metal hydride reagents act as a source of H– because they contain polar metal–
hydrogen bonds that place a partial negative charge on hydrogen.

Aluminum is less electronegative than boron, so more of the negative charge in the
AlH4- is borne by the hydrogen atoms. Therefore, lithium aluminum hydride (LiAlH4)
is more powerful reducing agent than sodium borohydride (NaBH4) and it is much
more difficult to work with than sodium borohydride. Lithium aluminum hydride
reacts violently with water, alcohols, and other protic solvents to liberate hydrogen
gas and form metal hydroxides and alkoxides. Therefore, reductions of aldehydes and
ketones using this reagent must be carried out in aprotic solvents, most commonly
diethyl ether or tetrahydrofuran. Sodium borohydride is safer to use as it reacts very
slowly with water or alcohol. Therefore, reductions using sodium borohydride are
most commonly carried out in aqueous methanol, in pure methanol, or in ethanol.
Both LiAlH4 and NaBH4 can be used to reduce reactive carbonyl compounds like
aldehyde, ketones and acid halides, but less reactive carbonyl compounds like
carboxylic acids, amides, esters can be reduced only by using LiAlH4; they cannot be
reduced with milder reducing agents like NaBH4. Therefore, NaBH4 being safer is
generally used to reduce aldehydes, ketones, and acid halides, while LiAlH4 being
more reactive is used to reduce carboxylic acids, esters, and amides.
Two other milder reagents are used to reduce these compounds.
 Diisobutylaluminum hydride (abbreviated as DIBAL-H), is less reactive
than LiAlH4 because of the two bulky isobutyl groups. Unlike LiAlH4, which
provides four H atom for reduction, DIBAL-H gives only one H atom for
reduction.
 Lithium tri-tert-butoxyaluminum hydride is less nucleophilic than LiAlH4.
The three hydrogen atoms of LiAlH4 are replaced by –OR groups, which
decreases its nucleophilic activity. Three electronegative oxygen atoms
bonded to aluminum makes aluminum more electronegative and thus reduce
electron density on hydride ion.

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LiAlH4 is a strong, non-selective reducing agent. NaBH4, DIBAL-H and Lithium tri-
tert-butoxyaluminum hydride are milder, more selective reducing agents.
Alkenes and alkynes are generally not affected by metal hydride reducing agents.
These reagents function as hydride ion donors, that is, as nucleophiles, and alkenes
and alkynes are not attacked by nucleophiles.

 Reduction of aldehydes, ketones and acid halides (or acyl halides) to alcohol -
Aldehydes, ketones, and acid halides can be reduced either by LiAlH4 or NaBH4.
But sodium borohydride is generally used for this purpose because it is milder,
selective and much safer than LiAlH4.
Reductions using sodium borohydride are most commonly carried out in aqueous
methanol, in pure methanol, or in ethanol. The initial product of reduction is a
tetraalkyl borate, which, on warming with water, is converted to an alcohol and
sodium borate salts. One mole of sodium borohydride reduces four moles of
aldehyde or ketone.

In case of lithium aluminum hydride, the reaction is carried out in aprotic

solvents, generally diethyl ether or tetrahydrofuran. One mole of lithium
aluminum hydride reduces four moles of aldehyde or ketone. After reduction, a
separate hydrolysis step is required to liberate the alcohol product. Because of the
formation of gelatinous aluminum salts, aqueous acid or base work-up is usually
used to dissolve these salts.

On reduction with LiAlH4 or NaBH4, aldehydes and acid halides produce primary
alcohol, while ketones give secondary alcohol.

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 Reduction of acid chloride to aldehyde – Strong reducing agents like LiAlH4

reduce acid chlorides all the way to primary alcohols. Lithium tri-tert-
butoxyaluminum hydride is a milder reducing agent that reacts faster with acid
chlorides than with aldehydes. Reduction of acid chlorides with lithium tri-tert-
butoxyaluminum hydride gives good yields of aldehydes.

 Reduction of carboxylic acid to alcohol - Lithium aluminum hydride, LiAlH4

(LAH), reduces a carboxylic acid to a primary alcohol in excellent yield, although
heating is required. LAH is usually dissolved in diethyl ether or tetrahydrofuran
(THF). When carboxylic acids react with LiAlH4, the initial product is a
tetraalkoxy aluminate ion, which is then treated with water to give the primary
alcohol and lithium and aluminum hydroxides. These hydroxides are insoluble in
diethyl ether and THF and are removed by filtration. Evaporation of the solvent
then yields the primary alcohol.

 Reduction of an ester to alcohol or aldehyde – Esters are more easily reduced than
carboxylic acids. Depending on the reducing agent, esters give either primary
alcohols or aldehyde. When treated with LiAlH4, a strong reducing agent, acyl
group of ester is cleaved to produce two alcohols, while diisobutylaluminum
hydride, [(CH3)2CHCH2]2AlH abbreviated as DIBAL-H, a mild reducing agent
reduces ester to aldehyde.

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In the reaction, CH3O- comes off as a leaving group, which on protonation gives
alcohol.
Mechanism of reduction of acid chloride and ester by LiAlH4:
Part 1: Nucleophilic substitution forms an aldehyde.

Part 2: Nucleophilic addition forms a primary alcohol.

First part of the reaction ended with the formation of aldehyde. If the reaction is
carried out by using LiAlH4, a strong reducing agent, aldehyde is further reduced to
form an alcohol. However, when DIBAL-H, a mild reducing agent, is used at a low
temperature the reduction of the ester can be stopped after the addition of one
equivalent of hydride ion. The reaction is carried out at -78oC to avoid further
reduction of aldehyde to alcohol. Hence the final products are an aldehyde and an
alcohol (formed by protonation of CH3O-, a leaving group).
 Reduction of epoxide to an alcohol – On treatment with LiAlH4, ethylene epoxide
is reduced to primary alcohol while substituted epoxides are reduced to secondary
alcohols because the hydride ion attacks preferentially at the less hindered carbon
of epoxide, consistent with SN2 mechanism.

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H2C CH2
(1) LiAlH4, ether
H3C CH2OH
(2) H+, H2O
O
Ethylene epoxide Ethanol

H2C CHCH3
(1) LiAlH4, ether H3C CHCH3
(2) H+, H2O
O OH
substituted epoxide propan-2-ol

 Reduction of amides – Unlike the LiAlH4 reduction of other carboxylic acid

derivatives, which results in the formation of primary alcohols, the LiAlH4
reduces amides to 1o, 2o and 3o amines depending upon the degree of substitution
of the amide. Both CO bonds are reduced to CH bonds. Because –NH2 (or –
NHR or –NR2) are poor leaving group, it remain intact during the reaction and
therefore the final product is amine.

This is widely used method for the synthesis of amines as the yield is very good
with no side products.
 Reduction of nitriles to primary amines – Nitriles are reduced to primary amines
by using LiAlH4 as reducing agent.

This is an important method for the preparation of amines and is used for
increasing the length of carbon chain during the synthesis of amine from
haloalkanes; alkyl halides are converted to nitriles by the reaction with KCN (or
NaCN), thereafter nitriles are reduced by catalytic hydrogenation or by LiAlH4 to
amines.
 Reduction of haloalkanes to alkanes – Haloalkanes are reduced, by using LiAlH4,
to alkanes with the loss of halide ion (X-) as a leaving group.

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Because H- is strong nucleophile, the reaction follows one-step SN2 mechanism.

Selective reductions
 Sodium borohydride cannot reduce following groups:
O O O O
C OH C OR C NH2
carboxylic acid ester amide epoxide

C C C C C N
H H
alkene alkyne nitrile
Therefore, it can be used to selectively reduce an aldehyde or a ketone group in a
compound that also contains a less reactive group. Acid is not used in the second
step of the following reaction, in order to avoid hydrolysis of the ester:

Note → LiAlH4 would reduce both keto and ester functions.

 The selective reduction of ester is not possible when the compound contains keto
or aldehyde functions because aldehydes and ketones are more reactive so they
will be reduced first.
Acetals are unreactive to bases, hydride reducing agents, Grignard reagents,
catalytic hydrogenation conditions, but they are cleaved by acids. Therefore, the
selective reduction of ester group is accomplished by first protecting the keto
group as an acetal, then reducing the ester with LiAlH4, and then removing the
acetal by treatment with aqueous acid.

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 The metal hydride reducing agents like LiAlH4 and NaBH4 being nucleophilic
reagent cannot reduce alkenes and alkynes because they are not electrophiles.
Therefore, selective reduction of a carbonyl group in presence of a carbon-carbon
double or triple bonds can be carried out by using metal hydrides without
affecting multiple bonds as long as they are not conjugated.

 Selective reduction of a carbon-carbon double in presence of carbonyl group can

be achieved by using rhodium on powdered charcoal as a catalyst.

 A chemoselective reaction is a reaction in which a reagent reacts with one

functional group in preference to another. For example, NaBH4 in isopropyl
alcohol reduces aldehydes faster than it reduces ketones.

On the other hand, ketones are reduced faster than aldehyde with NaBH4 in
aqueous ethanol at -15oC in presence of cerium trochloride.

4.3. Summary
 Oxidation is coupled with reduction: A reducing agent is oxidized and an oxidizing
agent is reduced.
 Oxidation results in an increase in the number of C–Z bonds (usually C–O bonds)
or a decrease in the number of C–H bonds.
 Reduction results in a decrease in the number of C–Z bonds (usually C–O bonds)
or an increase in the number of C–H bonds.
 The oxidation state of a carbon atom equals the total number of its C–O, C–N and
C–X bonds.

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 An organic compound is reduced by the addition of by one of three mechanisms:

Catalytic hydrogenations add two hydrogen atoms, dissolving metal reductions add
two electrons and two protons, and metal hydride reductions involve the addition
of a hydride ion followed by a proton.
 Multiple bonds can be reduced by catalytic hydrogenation.
 An alkyne is reduced by sodium and liquid ammonia to a trans alkene
 LiAlH4 is stronger reducing agent than NaBH4.
 NaBH4 is used to reduce aldehydes, ketones, and acyl halides; LiAlH4 is used to
reduce carboxylic acids, esters, and amides.
 Primary alcohols are oxidized to carboxylic acids by chromium-containing
reagents and to aldehydes by PCC or a Swern oxidation.
 A peroxyacid oxidizes an aldehyde to a carboxylic acid, a ketone to an ester (in a
Baeyer–Villiger oxidation), and an alkene to an epoxide.
 A regioselective reaction forms predominantly or exclusively one constitutional
isomer
 A stereoselective reaction forms predominantly or exclusively one stereoisomer.
 An enantioselective reaction affords predominantly or exclusively one enantiomer.
 Alkenes are oxidized to 1,2-diols by potassium permanganate (KMnO4) in a cold
basic solution or by osmium tetraoxide (OsO4).

4.4. Exercise
4.4.1. Draw the organic products formed in each hydrogenation.

4.4.2. Give the products of the following reactions.

4.4.3. Give the products of the following reactions:

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4.4.4. What stereoisomers would be formed from the reaction of each of the following
alkenes with OsO4 followed by H2O2?
(a) trans-2-butene
(b) cis-2-butene
(c) cis-2-pentene
(d) trans-2-pentene

Wollo University, Department of Chemistry, 2015