MSP Mondal’s
Deogiri College Aurangabad
MSc Organic Chemistry SY Third Semester
Organic Synthesis, CHEO-314
1. Oxidation
by
Mr. Anand V Dhirabassi
Assistant Professor
Department of Chemistry
Deogiri College Aurangabad
Content
* (A)Oxidation of alcohol to aldehyde, ketone or acid: Jones
reagent, Swern oxidation, Collins reagent, Fetizones
reagent, PCC, PDC, PFC, IBX, Activated MnO2, Chromyl
chloride (Etard reaction), TEMPO, CAN, NMO, Moffatt
oxidation
* (b)Oxidative cleavage of Carbon-Carbon double bonds:
KMnO4, Ozonolysis.
* (c)Allylic Oxidation: SeO2, PhSeBr.
* (d)Selective cleavages at functional groups: Cleavage of
glycols, IO-4, Pb(OAc)..
Introduction
* You are undoubtedly already familiar with the general idea of
oxidation and reduction: you learned in general chemistry that
when a compound or atom is oxidized it loses electrons, and
when it is reduced it gains electrons. You also know that
oxidation and reduction reactions occur in pairs: if one species is
oxidized, another must be reduced at the same time - thus the
term 'redox reaction'.
* In organic chemistry, redox reactions look a little different.
Electrons in an organic redox reaction often are transferred in the
form of a hydride ion - a proton and two electrons. Because they
occur in conjunction with the transfer of a proton, these are
commonly referred to as hydrogenation and dehydrogenation
reactions:
* When a carbon atom in an organic compound loses a bond to
hydrogen and gains a new bond to a heteroatom (or to another
carbon), we say the compound has been dehydrogenated, or
oxidized. A very common biochemical example is the
oxidation of an alcohol to a ketone or aldehyde:
* When a carbon atom loses a bond to hydrogen and gains a
bond to a heteroatom (or to another carbon atom), it is
considered to be an oxidative process because hydrogen, of all
the elements, is the least electronegative. Thus, in the process
of dehydrogenation the carbon atom undergoes an overall loss
of electron density - and loss of electrons is oxidation.
* Conversely, when a carbon atom in an organic compound gains a
bond to hydrogen and loses a bond to a heteroatom (or to another
carbon atom), we say that the compound has been hydrogenated,
or reduced. The hydrogenation of a ketone to an alcohol, for
example, is overall the reverse of the alcohol dehydrogenation
shown above. Illustrated below is another common possibility,
the hydrogenation (reduction) of an alkene to an alkane.
* Hydrogenation results in higher electron density on a carbon
atom(s), and thus we consider process to be one of reduction of
the organic molecule.
* Notice that neither hydrogenation nor dehydrogenation involves
the gain or loss of an oxygen atom. Reactions which do involve
gain or loss of one or more oxygen atoms are usually referred to
as 'oxygenase' and 'reductase' reactions,
* For the most part, when talking about redox reactions in organic
chemistry we are dealing with a small set of very recognizable
functional group transformations. It is therefore very worthwhile
to become familiar with the idea of 'oxidation states' as applied
to organic functional groups.
* By comparing the relative number of bonds to hydrogen atoms,
we can order the familiar functional groups according to
oxidation state. We'll take a series of single carbon compounds
as an example. Methane, with four carbon-hydrogen bonds, is
highly reduced. Next in the series is methanol (one less carbon-
hydrogen bond, one more carbon-oxygen bond), followed by
formaldehyde, formate, and finally carbon dioxide at the highly
oxidized end of the group.
* This pattern holds true for the relevant functional groups on
organic molecules with two or more carbon atoms:
* Alkanes are highly reduced, while alcohols - as well as alkenes,
ethers, amines, sulfides, and phosphate esters - are one step up
on the oxidation scale, followed by aldehydes/ketones/imines
and epoxides, and finally by carboxylic acid derivatives.
* Ethanol and ethene are considered to be in the same oxidation
state. You know already that alcohols and alkenes are
interconverted by way of addition or elimination of water. When
an alcohol is dehydrated to form an alkene, one of the two
carbons loses a C-H bond and gains a C-C bond, and thus is
oxidized. However, the other carbon loses a C-O bond and gains a
C-C bond, and thus is considered to be reduced. Overall,
therefore, there is no change to the oxidation state of the
molecule.
* You should learn to recognize when a reaction involves a change
in oxidation state in an organic reactant : an alcohol functional
group is converted to a ketone, which is one step up on the
oxidation ladder.
* The oxidation of an alcohol to form an aldehyde or ketone is
very important in synthesis. In this process, the hydroxy
hydrogen of the alcohol is replaced by a leaving group (X in the
figure below).
* Then, a base can abstract the proton bound to the alcohol
carbon, which results in elimination of the X leaving group and
formation of a new carbon-oxygen double bond. As you can
see by looking closely at this general mechanism, tertiary
alcohols cannot be oxidized in this way – there is no hydrogen
to abstract in the final step!
*
Jones Reagent
* The Jones Oxidation allows a relatively inexpensive conversion
of secondary alcohols to ketones. The Jones reagent is an
excellent reagent for the oxidation of secondary alcohols that do
not contain acid-sensitive group such as acetals.
* Jones described for the first time a conveniently and safe
procedure for a chromium (VI)-based oxidation,
CrO3 + dil. H2SO4 H2O HO-CrO2-OH (Jones reagent)
* Mechanism of the Jones Oxidation
* The Jones Reagent is a mixture of chromic trioxide or sodium
dichromate in diluted sulfuric acid, which forms chromic acid
in situ.
* The alcohol and chromic acid form a chromate ester that
either reacts intramolecularly or intermolecularly in the
presence of a base (water) to yield the corresponding
carbonyl compound:
* Examples
* Oxidation of primary alcohols to carboxylic acids.. Aldehydes
that can form hydrates in the presence of water are further
oxidized to carboxylic acids:
* Oxidation of primary alcohols with Jones reagent may result in
the conversion of the aldehydes initially formed to the
corresponding carboxylic acids. The reagent is added to the
alcohol contained in acetone at 0-25 °C,
Mechanism of Oxidation of Primary alcohol to carboxylic Acid by jones reagent.
* The oxidation of primary allylic and benzylic alcohols
gives aldehydes.
* Chromium can oxidize allylic alcohols to α,β-unsaturated
ketones on the opposite side of the unsaturated bond from
the alcohol. This is via a concerted hetero-Claisen reaction,
although there are mechanistic differences since the
chromium atom has access to d-orbitals which allow the
reaction under a less constrained set of geometries.
* Examples
Collins Reagent
* A solution of CrO3 • 2 Py (Sarett Reagent) in methylene
chloride is called the "Collins Reagent". One advantage over
the Sarett Reagent is that the addition of one equivalent
chromium trioxide to a stirred solution of two equivalents of
pyridine in methylene chloride allows the convenient and safe
preparation of the oxidant. Thus, most acid and base-sensitive
substrates can be oxidized with Collins Reagent, unlike Jones
Reagent.
* Preparation of Collins Reagent
* The reagent is prepared by adding CrO3 to a mixture of
pyridine-CH2Cl2 .
* As the Collins Reagent does not contain water (compared
to the Jones Reagent) and is not as hygroscopic as is the
Sarett Reagent, the oxidant is especially useful for the
oxidation of primary alcohols to aldehydes where traces of
water can lead to over oxidation.
* Mechanism of oxidation by collins reagent
* Examples
PCC (Pyridinium Chloro Chromate)
PFC (Pyridinium Fluoro Chromate)
* PCC/PFC is a milder version of chromic acid.
Essentially, what it does is oxidize alcohols one rung up
the oxidation ladder, from primary alcohols to aldehydes
and from secondary alcohols to ketones. Unlike chromic
acid, PCC will not oxidize aldehydes to carboxylic acids.
* Preparation of PCC Reagent
* PCC is used as an oxidant. In particular, it has proven to be
highly effective in oxidizing primary and secondary
alcohols to aldehydes and ketones, respectively. The reagent
is more selective than the related Jones reagent.
Mechanism of Oxidation by PCC
* Llll
* Example
* Tertiary Allylic alcohol Oxidized by PCC to gives
unsaturated ketone.
PDC (Pyridinium Dichromate)
* Pyridinium dichromate is the pyridinium salt of dichromate
that can be obtained by addition of pyridine to a solution
of chromium trioxide in water.
* The oxidation of alcohols by PDC (Pyridinium
Dichromate) works under mild conditions and can be used
for compounds containing unstable functional groups. This
method is useful to synthesize aldehydes.
* PDC is closer to neutral.
* Pyridinium dichromate (PDC), (C5H5NH)2Cr2O7 is an orange
colored solid used as an oxidizing agent.
* PDC is less acidic than PCC ( Pyridinium Chloro Chromate)
and hence is more suitable in the oxidation of acid sensitive
compounds.
Preparation of PDC
* Pyridinium dichromate, PDC can be obtained by gradual
addition of a solution of chromic anhydride (CrO3) in water to
pyridine in ice cold conditions.
* It is soluble in water, DMF and DMSO. But sparingly
soluble in CH2Cl2 or CH3Cl.
* The reaction conditions are mild and neutral. It can be
employed to oxidize compounds containing acid sensitive
functional groups.
* PDC is less acidic than PCC ( Pyridinium Chloro Chromate)
and hence is more suitable in the oxidation of acid sensitive
compounds.
* Mechanism of oxidation by PDC
* Examples of PDC oxidation
* Acid sensitive groups, such as enol ethers, are not
affected during the oxidation with PDC.
* .
* In DMF, the reaction of primary alcohols with PDC (except
for ally alcohols) leads to complete oxidation to carboxylic
acids. But in DCM reaction is stop at the aldehyde as
product only.
* PDC in CH2Cl2 or DMF is also called as Corey-Schmidt
reagent. In this case, PDC is maintained in anhydrous
conditions.
* Over oxidation mechanism of primary alcohol to
carboxylic acid by PDC In DMF as solvent
* Examples
* Non-conjugated primary alcohols are oxidized to carboxylic
acids with excess of PDC in moist DMF. But in
Dichloromethane, the oxidation stops at aldehyde level
only.
* However the conjugated primary alcohols are only oxidized
to aldehydes even in DMF.
Swern Oxidation
* The Swern oxidation, named after Daniel Swern, is
a chemical reaction whereby a primary or secondary alcohol
is oxidized to an aldehyde or ketone using oxalyl chloride,
dimethyl sulfoxide (DMSO) and an organic base, such as
triethylamine. It is one of the many oxidation reactions
commonly referred to as 'activated DMSO' oxidations. The
reaction is known for its mild character and wide tolerance
of functional groups.
* Dichloromethane is usually the solvent of choice for this
reaction, but Et2O or THF may also be used.
* For secondary alcohols, warming the reaction to -40 °C
after the addition of the alcohol for 20 min may help.
* Base is must for the oxidation.
* Mechanism of Swern oxidation
* Examples
Moffatt Oxidation
* The Pfitzner–Moffatt oxidation, sometimes referred to as
simply the Moffatt oxidation, is a chemical reaction for
the oxidation of primary and secondary alcohols to aldehydes
and ketones, respectively. The oxidant is a combination
of dimethyl sulfoxide (DMSO) and dicyclohexylcarbodiimide
(DCC).
*
* Mechanism of Moffatt Oxidation
Examples
Parikh – Doering Oxidation reaction : Modified reaction
of Moffatt oxidation. DMSO – SO3 mediated reaction.
* Omura- Sharma- Swern Oxidation reaction : Modified
reaction of Moffatt oxidation. DMSO –TFAA mediated
reaction.
* Albright-Goldman Oxidation reaction : Modified
reaction of Moffatt oxidation. DMSO –Aceticunhydride
mediated reaction.
Etard Oxidation
* The Etard reaction is an organic transformation in which a
methyl group (-CH3) bonded to an aromatic (benzene) ring
undergoes an oxidation reaction and becomes an aldehyde
functional group. Consider as an example the oxidation of
toluene to produce benzaldehyde. The general reaction looks
like:
* The specific oxidizing agent the Etard reaction employs is
chromyl chloride. Chromyl chloride is a chromium-based,
mild oxidizing agent that is excellent at making aldehydes.
* Reaction:
* Mechanism of Etard Oxidation Reaction
* Examples of Etard Oxidation
* 2-Methylfuran can also participate in the Etard reaction, and
the product is furfural, which itself is an industrially and
synthetically useful organic building block.
* Organic compounds that contain nitrogen atoms can also
undergo an Etard reaction. For example, 2-methylpyridine
can be taken and transformed into 2-formylpyridine easily
by virtue of the Etard reaction
Iodoxybenzoic Acid (IBX)
* A mild and efficient oxidation of alcohols with o-
iodoxybenzoic acid (IBX) is catalyzed by β-cyclodextrin
in a water/acetone mixture (86:14). Various alcohols
were oxidized at room temperature in excellent yields.
* Preparation of IBX
* IBX is prepared from 2-iodobenzoic acid, potassium
bromate, and sulfuric acid.
* IBX oxidized secondary alcohol to Ketone.
IBX Oxidized Primary alcohol to aldehyde
Mechanism of IBX Oxidation
* Selective oxidation of secondary hydroxyl groups in the
presence of primary hydroxyl groups is possible.
* IBX also oxidized ketone into the α-β unsaturated ketone
while using more equivalent of IBX.
* Mechanism
* Oxidative cleavage of diols by IBX
* IBX is notable for oxidizing vicinal diols (or glycols) to
diketones without cleavage of the carbon-carbon bond, but
oxidative cleavage of glycols to two aldehydes or ketones
can occur when modified conditions are used (elevated
temperatures or trifluoroacetic acid solvent)
* Mechanism of oxidative cleavage of diols by IBX
* Examples
Dess Martine Periodinate (DMP)
* Alcohols can be oxidized to aldehydes, ketones, and
carboxylic acids depending on their structure and the type of
oxidizing agent. In general, we can classify oxidizing agents
as strong and mild. Soluble with organic solvent than IBX.
* Mild oxidizing reagents stop the oxidation of the alcohol once
the carbonyl group is formed. And if the alcohol is a primary,
the product is an aldehyde while the oxidation of a secondary
alcohol results in a ketone.
* This periodinane has several advantages over chromium-
and DMSO-based oxidants that include milder conditions
(room temperature, neutral pH), shorter reaction times, higher
yields, simplified workups, high chemoselectivity, tolerance
of sensitive functional groups, and a long shelf life. However,
use on an industrial scale is made difficult by its cost and its
potentially explosive nature.
* Preparation of DMP.
*
* Dess–Martin periodinane (DMP oxidation) is a selective
method for oxidizing primary alcohols to aldehydes.
Secondary alcohol to ketone.
* Mechanism of DMP Oxidation
* When a diol or more than one equivalent of alcohol is used,
acetoxydialkoxyperiodinane is formed instead. Due to
the labile nature of this particular periodinane, oxidation
occurs much faster.
* Examples of DMP Oxidation
