Download Redox Reactions

Chemistry 213
Clark College
Redox Reactions: A Review
Redox reactions are plentiful in organic chemistry as we learn to selectively convert one functional
group into another. We will review most of the redox reactions we have learned thus far, consider
some new reactions, and focus on selectively reducing or oxidizing one functional group in the
presence of others.
Reductions
To an organic chemist, a reduction reaction is the process of adding a molecule of H2 to a molecule,
typically to a pi bond. This can be achieved in three different ways:
1) Addition of H2 – catalytic hydrogenation. This method uses a metal catalyst to add H2 gas to a
molecule. This works primarily on nonpolar and slightly polar molecules.
2) Addition of 2e-, 2H+. This method uses alkali metals as an electron source in conjunction with a
protic solvent.
3) Addition of H-, H+ – hydride reagents. Hydride reactions are nucleophilic reactions that reduce
polar compounds. They are typically followed by an aqueous or acidic work-up that provides
the proton.
Addition of H2
These reductions rely on transition metal catalysts to split a molecule of H2 and to provide a template
for the pi bond and the H atom to react. Since they happen on the surface of the metal catalyst, the
addition of H2 is a syn addition, with both H atoms adding to the same face of the pi bond.
For most functional groups, a whole host of transition metals will work as catalysts. The traditional
catalysts are Pt, Pd, or Ni.
H2
Pt, Pd or Ni
Carbon-Carbon bonds:
H2
Pt, Pd or Ni
H2
Lindlar's Catalyst
C N
H2
Ni
R C N
H2
Ni
Carbon-Nitrogen bonds:
O
Carbon-Oxygen bonds:
R
H
H2
Ni
R'
H2
Ni
O
R
Redox Review Notes
*Lindlar's catalyst is a "poisoned"
Pd catalyst - Pd/CaCO3, Pb2+
H C N
H2
R C
R
H
NH2
OH
OH
R
R'
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Chemistry 213
Clark College
Since many functional groups can be reduced with H2 and a metal catalyst, how do we get selectivity?
One method would be to protect an aldehyde or ketone, perform the reduction, and then deprotect the
carbonyl. However, this takes 3 synthetic steps, and is not an option for the nitrogen functional groups.
To selectively reduce an alkene, in the presence of another functional group, a rhodium catalyst is
employed.
O
O
H2
Rh
Addition of 2e-, 2H+
Alkali metal reductions are used for the stereochemistry of the reduction: the addition of an electron to
each side of the double bond forces a “trans” configuraton of the addition of H2.
Na0
NH3, -78°C
Addition of H-, H+
Hydride reagents provide H- as a nucleophile, therefore they only react with polar substrates containing
an electrophile. They do not react with alkenes or alkynes, so they provide additional selectivity
between the functional groups. The reaction mechanism involves the nucleophilic attack of the
carbonyl carbon by H-, creating an O-. An acid or aqueous work-up protonates the O- to form the
alcohol.
Sodium borohydride (NaBH4) is a milder reducing agent that is easier to use, but less reactive. It reacts
only with the most reactive carbonyl compounds – aldehydes, ketones and some acid chlorides.
O
H
1) NaBH4
2) H3O+
O
1) NaBH4
2) H3O+
O
1) NaBH4
2) H3O+
Cl
OH
OH
*Acid chlorides are the
OH only acid derivative that
will react with NaBH4.
In order to reduce the less-reactive acids and derivatives, a stronger, more polar reducing agent is
used: Lithium aluminum hydride (LiAlH4). This reagent is extremely reactive and air and moisture
sensitive, and is used only when required by the starting material.
O
OEt
O
NH2
1) LiAlH4
2) H2O
OH
1) LiAlH4
2) H2O
NH2
Note that imines and nitriles are also reduced to amines by lithium aluminum hydride. Acid derivatives
are reduced all the way to the alcohol with LiAlH4. Is there a way to stop at the aldehyde, and reduce
these molecules “half-way”? The reduction still requires a hydride reagent, but one that has been
modified to control stoichiometry. This reagent, DIBALH, is also used specifically with esters, which
have a lower reactivity than other acid derivatives.
Redox Review Notes
Page 2 of 4
Chemistry 213
O
OEt
Clark College
1) DIBALH,
-78°C
2) H2O
O
DIBALH = diisobutyl aluminum hydride =
H
Al
H
If we look back at the carbonyl reductions, most (except the nitrogen-containing compounds) convert
the carbonyls to alcohols, so the oxygen in the molecule is retained. There are two reductions that
convert carbonyls down to a –CH2– group, completely removing the oxygen. These reductions work
specifically on aldehydes and ketones, and differ by being in either acidic or basic conditions, which
allow for compatibility with other functional groups.
O
Clemmensen Reduction
H
O
Wolff-Kishner Reduction
H
Zn(Hg)
HCl
H
H
N2H4
KOH
A summary
CN
H2N
H2
Ni
O
O
Et
O
OH
CN
Redox Review Notes
Et
NH2
1) LiAlH4
2) H2O
1) NaBH4
2) H3O+
O
O
O
Et
O
H2
Rh
CN
O
OH
OH
O
O
Et
OH
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Chemistry 213
Clark College
Oxidation Reactions
The oxidation reactions that we will review will not be adding initial oxygens to a molecule, rather most
will increase bonding to existing oxygens or adding secondary ones. We will first consider the various
chromium oxidations, and then look at an aldehyde-specific reaction – the Tollens’ test. We need to
remember that for an oxidation to take place, there needs to be a hydrogen on the carbon attached to
the oxygen – 3° alcohols and ketones cannot be oxidized because they lack this hydrogen.
Chromium Oxidations
The most common, and strongest oxidizing agent is chromic acid, H2CrO4. This reagent is often
generated in situ by dissolving either CrO3 or K2Cr2O7 in aqueous acidic solution. Because of the
aqueous medium that the reactions take place in, chromic acid oxidations are complete – each starting
material is oxidized to the highest possible oxidation state. To stop at an intermediate oxidation state,
chromium can still be employed, however water must be removed. An alternate reagent, pyridinium
chlorochromate (PCC) has been developed to satisfy these requirements. The table below
summarizes chromium oxidations.
OH
PCC
pyridine
O
O
H2CrO4
H
OH
H2CrO4
OH
H2CrO4
O
or PCC/pyr
Tollens’ Test
The Tollens test is a reaction that is specific to aldehydes – the reaction selectively oxidizes aldehydes
to carboxylic acids. This reaction is commonly used as a chemical tests for aldehydes and reducing
sugars (which contain aldehyde functional groups) as the byproduct of the reaction is metallic silver
which coats the reaction vessel with a mirror.
O
H
Redox Review Notes
1) Ag+, NH3
2) H3O+
O
OH
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