Chemistry, Organic Second Edition
Janice Gorzynski Smith
University of Hawaii
Chapter 12
Lecture Outline
Prepared by Rabi Ann Musah
State University of New York at Albany
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1
Oxidation and Reduction
Introduction
Recall that oxidation results in an increase in the number
of CZ bonds (usually CO bonds) or a decrease in the
number of CH bonds.
Recall that reduction results in a decrease in the number of
CZ bonds (usually CO bonds) or an increase in the
number of CH bonds.
Figure12.1
A general scheme for the
oxidation and reduction of
a carbon compound
2
Oxidation and Reduction
Introduction
Sometimes two carbon atoms are involved in a single
oxidation or reduction reaction, and the net change in the
number of CH or CZ bonds at both atoms must be
taken into account.
The conversion of an alkyne to an alkene, or an alkene
to an alkane are examples of reduction because each
process adds two new CH bonds to the starting
material.
Figure12.2
Oxidation and reduction of
hydrocarbons
3
Oxidation and Reduction
Reducing Agents
There are three types of reductions differing in how H2 is
added.
The simplest reducing agent is H2. Reductions using H2
are carried out with a metal catalyst.
A second way is to add two protons and two electrons to
a substratethat is, H2 = 2H+ + 2e-.
Reductions of this sort use alkali metals as a source
of electrons, and liquid ammonia as a source of
protons.
These are called dissolving metal reductions.
4
Oxidation and Reduction
Reducing Agents
The third way to add H2 is to add hydride (H) and a
proton (H+).
The most common hydride reducing agents contain a
hydrogen atom bonded to boron or aluminum. Simple
examples include sodium borohydride (NaBH4) and
lithium aluminum hydride (LiAlH4).
NaBH4 and LiAlH4 deliver H to the substrate, and then a
proton is added from H2O or an alcohol.
5
Oxidation and Reduction
Reduction of AlkenesCatalytic Hydrogenation
The addition of H2 occurs only in the presence of a metal
catalyst, and thus it is called catalytic hydrogenation.
The catalyst consists of a metalusually Pd, Pt, or Ni, adsorbed
onto a finely divided inert solid, such as charcoal.
H2 adds in a syn fashion.
6
Oxidation and Reduction
Reduction of AlkenesCatalytic Hydrogenation
The Ho of hydrogenation, also known as the heat of
hydrogenation, can be used as a measure of the relative stability
of two different alkenes that are hydrogenated to form the same
alkane.
When hydrogenation of two alkenes gives the same alkane, the
more stable alkene has the smaller heat of hydrogenation.
7
Oxidation and Reduction
Reduction of AlkenesCatalytic Hydrogenation
8
Oxidation and Reduction
Reduction of AlkenesCatalytic Hydrogenation
The mechanism explains two facts about hydrogenation:
9
Oxidation and Reduction
Reduction of AlkenesCatalytic Hydrogenation
When unsaturated vegetable oil is treated with hydrogen, some
or all of the bonds add H2. This increases the melting point of
the oil.
Margarine is prepared by partially hydrogenating vegetable oils
to give a product with a consistency that more closely resembles
butter.
Figure12.4
Partial
hydrogenation of
the double bonds
in a vegetable oil
10
Oxidation and Reduction
Reduction of Alkynes
There are three different ways in which H 2 can add to the triple
bond:
11
Oxidation and Reduction
Reduction of an Alkyne to an Alkane
Alkane formation:
12
Oxidation and Reduction
Reduction of an Alkyne to a Cis Alkene
Palladium metal is too reactive to allow hydrogenation of
an alkyne to stop after one equivalent of H2 adds.
To stop at a cis alkene, a less active Pd catalyst is used
Pd adsorbed onto CaCO3 with added lead(II) acetate and
quinoline. This is called Lindlars catalyst.
Compared to Pd metal, the Lindlar catalyst is deactivated
or poisoned.
With the Lindlar catalyst, one equivalent of H2 adds to an
alkyne to form the cis product. The cis alkene product is
unreactive to further reduction.
13
Oxidation and Reduction
Reduction of an Alkyne to a Cis Alkene
Reduction of an alkyne to a cis alkene is a stereoselective
reaction, because only one stereoisomer is formed.
14
Oxidation and Reduction
Reduction of an Alkyne to a Trans Alkene
In a dissolving metal reduction (such as Na in NH3), the
elements of H2 are added in an anti fashion to form a trans
alkene.
15
Oxidation and Reduction
Reduction of an Alkyne to a Trans Alkene
16
Oxidation and Reduction
Reduction of an Alkyne to a Trans Alkene
Dissolving metal reduction of a triple bond with Na in NH3 is a
stereoselective reaction because it forms a trans product
exclusively.
Dissolving metal reductions always form the more stable trans
product preferentially.
The trans alkene is formed because the vinyl carbanion
intermediate that is formed is more stable when the larger R
groups are further away from each other to avoid steric
interactions. Protonation of this anion leads to the more stable
trans adduct.
17
Oxidation and Reduction
Summary of Alkyne Reductions
Figure12.5
Summary: Three methods to
reduce a triple bond
18
Oxidation and Reduction
Reduction of Polar CX Bonds
Alkyl halides can be reduced to alkanes with LiAlH 4.
Epoxide rings can be opened with LiAlH4 to form alcohols.
Figure12.6
xamples of reduction of C X
bonds with LiAIH4
19
Oxidation and Reduction
Reduction of Polar CX Bonds
This reaction follows an SN2 mechanism.
Unhindered CH3X and 1 alkyl halides are more easily reduced
than more substituted 2 and 3 halides.
In unsymmetrical epoxides, nucleophilic attack of H (from
20
LiAlH4) occurs at the less substituted carbon atom.
Oxidation and Reduction
Oxidizing Agents
There are two main categories of oxidizing agents:
1. Reagents that contain an oxygen-oxygen bond
2. Reagents that contain metal-oxygen bonds
Oxidizing agents containing an OO bond include O2, O3
(ozone), H2O2 (hydrogen peroxide), (CH3)COOH (tert-butyl
hydroperoxide), and peroxyacids.
Peroxyacids (or peracids) have the general formula
RCO3H.
Figure12.7
Common peroxyacids
21
Oxidation and Reduction
Oxidizing Agents
The most common oxidizing agents with metal-oxygen bonds
contain either chromium +6 (six CrO bonds) or manganese
+7 (seven MnO bonds).
Common Cr6+ reagents include CrO3 and sodium or potassium
dichromate (Na2Cr2O7 and K2Cr2O7). Pyridinium chlorochromate
(PCC) is a more selective Cr6+ oxidant.
The most common Mn7+ reagent is KMnO4 (potassium
permanganate).
Other oxidizing agents that contain metals include OsO4
(osmium tetroxide) and Ag2O [silver(I) oxide]. 22
Oxidation and Reduction
Oxidizing Reactions
Figure12.8
Oxidation reactions of alkenes,
alkynes, and alcohols
23
Oxidation and Reduction
Epoxidation
Epoxidation is the addition of a single oxygen atom to an alkene
to form an epoxide.
Epoxidation is typically carried out with a peroxyacid.
24
Oxidation and Reduction
Epoxidation
Epoxidation occurs via syn addition of an O atom to
either side of a planar double bond. Thus, a cis alkene
gives an epoxide with cis substituents. A trans alkene
gives an epoxide with trans substituents.
Epoxidation is stereospecific because cis and trans
alkenes yield different stereoisomers as products.
25
Oxidation and Reduction
The Synthesis of Disparlure
Disparlure, the sex pheromone of the gypsy moth, is synthesized
by a stepwise sequence that uses an epoxidation reaction as the
final step.
Retrosynthetic analysis of disparlure illustrates three key
operations:
26
Oxidation and Reduction
The Synthesis of Disparlure
Figure12.9
The synthesis of disparlure
27
Oxidation and Reduction
Dihydroxylation
is Dihydroxylation the addition of two hydroxy groups to
a double bond, forming a 1,2-diol or glycol.
Depending on the reagent, the two new OH groups can
be added to the opposite sides (anti addition) or the
same side (syn addition) of the double bond.
28
Oxidation and Reduction
Dihydroxylation
Anti dihydroxylation is achieved in two stepsepoxidation,
followed by ring opening with OH or H3O+.
29
Oxidation and Reduction
Dihydroxylation
Syn hydroxylation results when an alkene is treated with
either KMnO4 or OsO4.
30
Oxidation and Reduction
Dihydroxylation
Each reagent adds two oxygen atoms in a syn fashion.
Hydrolysis of the cyclic intermediate cleaves the metal oxygen
bonds, forming a cis-1,2-diol.
31
Oxidation and Reduction
Dihydroxylation
Dihydroxylation can also be carried out by using a catalytic
amount of OsO4, if the oxidant N-methylmorpholine N-oxide
(NMO) is also added.
In the catalytic process, dihydroxylation of the double bond
converts the Os8+ oxidant into an Os6+ product, which is then reoxidized by NMO to Os8+.
32
Oxidation and Reduction
Oxidative Cleavage of Alkenes
Oxidative cleavage of an alkene breaks both the and bonds
of the double bond to form two carbonyl compounds. Cleavage
with ozone (O3) is called ozonolysis.
33
Oxidation and Reduction
Oxidative Cleavage of Alkenes
Addition of O3 to the bond of an alkene forms an unstable
intermediate called a molozonide, which rearranges to an
ozonide in a stepwise process.
The unstable ozonide is reduced to afford carbonyl compounds.
Zn (in H2O) or dimethylsulfide (CH3SCH3) are two common
reagents used to convert the ozonide into carbonyl compounds.
34
Oxidation and Reduction
Oxidative Cleavage of Alkenes
Ozonolysis of dienes or other polyenes results in oxidative
cleavage of all C=C bonds.
It is important to note that when oxidative cleavage involves a
double bond that is part of a ring, the ring opens up affording a
single chain with two carbonyls at the carbons where the double
bonds were originally.
35
Oxidation and Reduction
Oxidative Cleavage of Alkynes
Alkynes undergo oxidative cleavage of the and both
bonds.
Internal alkynes are oxidized to carboxylic acids (RCOOH).
Terminal alkynes afford a carboxylic acid and CO2 from the
sp hybridized CH bond.
36
Oxidation and Reduction
Oxidation of Alcohols
Alcohols are oxidized to a variety of carbonyl compounds.
37
Oxidation and Reduction
Oxidation of Alcohols
Recall that the oxidation of alcohols to carbonyl compounds is
typically carried out with Cr6+ oxidants, which are reduced to Cr3+
products.
CrO3, Na2Cr2O7, and K2Cr2O7 are strong, nonselective oxidants
used in aqueous acid (H2SO4 + H2O).
PCC is soluble in CH2Cl2 (dichloromethane) and can be used
without strong acid present, making it a more selective, milder
oxidant.
38
Oxidation and Reduction
Oxidation of 2 Alcohols
Any of the Cr6+ oxidants effectively oxidize 2 alcohols to
ketones.
39
Oxidation and Reduction
Oxidation of 1 Alcohols
1 Alcohols are oxidized to either aldehydes
carboxylic acids, depending on the reagent.
40
or
Oxidation and Reduction
Oxidation of 1 Alcohols
41
Oxidation and Reduction
Oxidation of 1 Alcohols
Cr6+ oxidations are characterized by a color change, as the redorange Cr6+ reagent is reduced to green Cr3+.
Some devices used to measure blood alcohol content make use
of this color changeOxidation of CH3CH2OH, the 1 alcohol in
alcoholic beverages, with orange K2Cr2O7 forms CH3COOH and
green Cr3+.
Blood alcohol level can be determined by having an individual
blow into a tube containing K2Cr2O7, H2SO4, and an inert solid.
The alcohol in the exhaled breath is oxidized by the Cr6+ reagent,
which turns green in the tube.
The higher the concentration of CH3CH2OH in the breath, the
more Cr6+ is reduced, and the farther the green Cr3+ color extends
down the length of the sample tube.
The extent of the green color is then correlated with blood
42
alcohol levels.
Oxidation and Reduction
Oxidation of 1 Alcohols
Figure12.10
Blood alcohol screening
43
Oxidation and Reduction
Green Chemistry
Green chemistry is the use of environmentally benign
methods to synthesize compounds.
Its purpose is to use safer reagents and less solvent, and
develop reactions that form fewer by-products and generate
less waste.
Since many oxidation methods use toxic reagents (such as
OsO4 and O3) and corrosive acids such as H2SO4, or generate
carcinogenic by-products (such as Cr3+), alternative less
problematic regents have been developed.
One methods uses a polymer supported Cr3+ reagent
Amberlyte A-26 resin-HCrO4that avoids the use of strong
acid, and forms a Cr3+ by-product that can easily be removed
from the product by filtration.
The Amberlyte A-26 resin consists of a complex hydrocarbon
network with cationic ammonium ion appendages that serve
44
as counterions to the anionic chromium agent, HCrO .
Oxidation and Reduction
Green Chemistry
Heating the insoluble polymeric reagent with an alcohol
results in oxidation to a carbonyl compound, with
formation of an insoluble Cr3+ by-product which can be
regenerated and reused in a subsequent reaction.
45
Oxidation and Reduction
Green Chemistry
With Amberlyst A-26 resin-HCrO4, 1 alcohols are
oxidized to aldehydes and 2 alcohols are oxidized to
ketones.
46
Oxidation and Reduction
Applications: The Oxidation of Ethanol
In the body, ingested ethanol is oxidized in the liver first to
CH3CHO (acetaldehyde), and then to CH3COO (the acetate
anion).
This oxidation is catalyzed by alcohol dehydrogenase.
If more ethanol is ingested than can be metabolized, the
concentration of acetaldehyde increases. Acetaldehyde, which is
toxic, is responsible for the feelings associated with a hangover.
If methanol is ingested, it is metabolized by the same enzyme to
formaldehyde and formic acid. These compounds are extremely
toxic since they cannot be used by the body. Blood pH
decreases, and blindness and death can follow.
47
Oxidation and Reduction
The Sharpless Epoxidation
Recall that in the reactions we have discussed thus far,
an achiral starting material has reacted with an achiral
reagent to give either an achiral product, or a racemic
mixture of two enantiomers.
48
Oxidation and Reduction
The Sharpless Epoxidation
In the Sharpless epoxidation, the double bonds of allylic alcohols
are oxidized to epoxides.
Since the formation of only one enantiomer is favored, the
reaction is said to be enantioselective.
An enantioselective reaction affords predominantly or
exclusively one enantiomer.
A reaction that converts an achiral starting material into
predominantly one enantiomer is called an asymmetric reaction.
49
Oxidation and Reduction
The Sharpless Epoxidation
The Sharpless reagent consists of three different
components: tert-butylhydroperoxide (CH3)3COOH; a titanium
catalystusually titanium(IV) isopropoxide, Ti[OCH(CH3)2]4;
and diethyl tartrate (DET).
There are two different chiral diethyl tartrate isomers, labeled
as (+)-DET or (-)-DET to indicate the direction in which they
rotate plane polarized light.
The identity of the DET isomer determines which enantiomer
is the major product obtained in the epoxidation.
50
Oxidation and Reduction
The Sharpless Epoxidation
Reactions [1] and [2] are highly enantioselective as each has
an enantiomeric excess of 95% (i.e., 97.5% of the major
5
enantiomer and 2.5% of the minor enantiomer). 1
Oxidation and Reduction
The Sharpless Epoxidation
To determine which enantiomer is formed from a given isomer
of DET, draw the allylic alcohol in a plane, with the OH group
in the bottom right hand corner; then note that:
52