University College of Pharmacy,

University of the Punjab, Lahore

Unit 9: CARBONIUM IONS

REARRANGEMENTS
Carbonium Ion:

 Carbonium ion is any action that has a pentavalent carbon atom.

 The name carbonium may also be used for the simplest member of the class,
properly called methanium (CH+5), where the five valences are filled
with hydrogen atoms.
 The current definitions were proposed by the chemist George Andrew Olah in
1972.

Preparation:

Carbonium ions can be obtained by treating alkanes with very strong

acids. Industrially, they are formed in the refining of petroleum during primary
thermal cracking.

Rearrangement Reaction:

 The term “rearrangements” is used to describe organic reactions which

involve the migration of a Hydrogen atom or of a larger molecular fragment.
 A rearrangement reaction is a broad class of organic reactions where the
carbon skeleton of a molecule is rearranged to give a structural isomer of the
original molecule.

There are three types of rearrangements in organic chemistry.

 Carbonium ion rearrangement

 Carbanion rearrangements
 Radical rearrangements

Carbonium Ion Rearrangement:

Carbonium ion rearrangement may be of two types:
Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
 Without change in carbon skeleton (Allylic rearrangement)
 With change in carbon skeleton
o Neopentyl rearrangement
o Pinacol-pinacolone rearrangement
o Wolf rearrangement
o Rearrangement of hydrocarbons

“Wagner-Meerwein Rearrangement”
Introduction:

 The rearrangements involving change in carbon skeleton are collectively

known as Wagner-Meerwein rearrangements.
 A Wagner-Meerwein rearrangement is a class of carbocation 1, 2 rearrange-
ment reactions in which a hydrogen, alkyl or aryl group migrates from one
carbon to a neighboring carbon.
 The rearrangement was first discovered in bicyclic terpenes for example the
conversion of isoborneol to camphene.

Definition:
Wagner-Meerwein Rearrangements are [1,2]- rearrangements of H atoms or
alkyl groups in carbonium ions that do not contain any heteroatom attached to the
valence-saturated center C-1 or to the valence-unsaturated center C-2.
1 1
R(H) R(H)
+
C C+ C C
1' 2' 1' 2'

For example “Neopentyl rearrangement”

Neopentyl Rearrangement:
The driving force for the actual migration of a substituent in step two of the
rearrangement is the formation of a more stable intermediate. For instance a tertiary
carbocation is more stable than a secondary carbocation and therefore the SN1
reaction of neopentyl bromide with ethanol yields tert-pentyl ethyl ether.

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore

The neopentyl alcohol after rearrangement can be converted into two major
forms.

Example:

1-Bromopropane isomerizes quantitatively to 2-bromopropane under Friedel-

Crafts conditions. The [1, 2]-shift A→B involved in this reaction again is an H-atom
shift.

Wagner-Meerwein rearrangement as a part of Isomerizing E1

elimination:

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore

Conversion of p-xylene to m-xylene:

In the presence of acid methyl group moves to meta position, which is

energetically more stable.

Example:

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore

“Pinacol-Pinacolone Rearrangements”
Definition:

 The conversion of an alcohol having two adjacent OH groups (pinacol) to a

ketone (pinacolone) by the action of acid is known as Pinacol-pinacolone
rearrangement.
 The pinacol–pinacolone rearrangement is a method for converting a 1,2-
diol to a carbonyl compound in organic chemistry. The 1,2-
rearrangement takes place under acidic conditions. The name of the
rearrangement reaction comes from the rearrangement
of pinacol to pinacolone.

General Reaction:

Mechanism:

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Mechanism of the pinacol rearrangement of a symmetrical glycol is as follows.

In the course of this organic reaction, protonation of one of the –OH groups
occurs and a carbocation is formed. If both the –OH groups are not alike, then the
one which yields a more stable carbocation participates in the reaction.
Subsequently, an alkyl group from the adjacent carbon migrates to the carbocation
center. The driving force for this rearrangement step is believed to be the relative
stability of the resultant oxonium ion, which has complete octet configuration at all,
centers (as opposed to the preceding carbocation). The migration of alkyl groups in
this reaction occurs in accordance with their usual migratory aptitude, i.e.
hydride > Phenyl > tertiary carbocation (if formed by migration) > secondary
carbocation (if formed by migration) > methyl cation . The conclusion which group
stabilizes carbocation more effectively is migrated.

Facts:

 1, 2 shift takes place in carbonium ion which is already a tertiary carbonium

ion.
 It is probably due to stabilization of rearranged ion that can be affected by
delocalization involving the electron pair on the oxygen atom, and ready loss
of proton from the oxygen to produce a stable end product.

The stable cation formed superior for stabilization.

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Bromohydrin to Pinacolone:

Hydroxyamine to Pinacolone:

Facts:

 It seems that migration of alkyl group is extremely fast on the loss of leaving
group, taking place simultaneously
 That migrating group is from the opposite side of the leaving group
o Because rearrangement is much more easy in compounds having trans
configuration than that having cis configuration

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Pinacol Rearrangement of an Asymmetrical Glycol:
Me Ph Me
Ph O Me
H2SO4
HO OH HO + Ph
Me Ph Me Ph Me Ph
A B C

Me Ph
+ OH
Me Ph
D
Et Ph Et Ph O Et
H2SO4
HO OH HO + _ + Ph
Ph H
Et Ph Et Et Ph
E F

Which group migrates?

Phenyl group move first because of greater chances of

stabilization due to delocalization

The steric chemistry of Pinacol Rearrangements:

 It is found that o-MeOPh migrate more than a 1000 time less readily that p-
substituent and even much less than phenyl. This is due to interference in the
transition state with non-migrating group.

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Explain the following Experimental facts:
R R R
R
R
C R +
H2SO4 O O
OH OH
(A) (B) (C)

When R = CH3, (B) and (C) are formed; when R = Ph, only (C) is formed.

When R=Me:
R R
+ C R
C R
+O H 2 OH OH
(1) (2)
R R
+ +
C R -H C R
R
+
+H :O H O
C R (3) (B)
OH OH
R R
(A)
+
C R C R
+ OH2
OH
(4) OH (5)
R + R
-H
+ R R
:O H
(6) O (C)

When R=Ph:

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore

“Wolff Rearrangement”
Definition:

 The Wolff rearrangement is a reaction in organic chemistry in which an α-

diazocarbonyl compound is converted into a ketene by loss of dinitrogen with
accompanying 1,2-rearrangement.
 It involves migration of a substituent to an uncharged, electron deficient,
carbon atom called carbene.
o That is a molecule containing a neutral carbon atom with two unshared
valence electrons. The general formula is RR'C.
 The term "carbene" may also refers to the compound H2C:, also called
methylene
 Carbenes are classified as either singlets or triplets depending upon their
electronic structure
 Most of the carbenes are very short lived, although persistent carbenes are
known.

Common Reaction:

 In this rearrangement α-diazoketones lose nitrogen to form highly reactive

ketenes.

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Example with Mechanism:
R C CHN2

R
C CH N N
**
+
O -N2

R R
C C C CH
**
H
O O

Two aspects of the mechanism can be agreed upon. First, α-diazocarbonyl

compounds are in an equilibrium of s-cis and s-trans-conformers, the distribution of
which may influence the mechanism of the reaction. Generally, under photolysis,
compounds in the s-cis conformation react in a concerted manner due to
the antiperiplanar relationship between the leaving and migrating groups, whereas
compounds in the s-trans conformation react stepwise through a carbene
intermediate or do not rearrange. Second, regardless of the reaction mechanism, the
rearrangement gives a ketene intermediate, which can be trapped by a weakly acidic
nucleophile, such as an alcohol or amine, to give the corresponding ester or amide,
or an olefin, to give a [2+2] cycloaddition adduct. Strong acids do not rearrange, but
rather protonate the α-carbon and give SN2 products.

Applications:
 Synthesis of analogues of carboxylic acids
 Synthesis of acid amides from carboxylic acids
 Synthesis of esters from carboxylic acids
SOCl2
R C OH R C Cl
O O CH2N2

R
C CH N N
** +
O -N2

R R
C C C CH
**
H
O O
CH OH

NH
H2O
3

3
O
O
O R-CH2-C-NH2
R-CH2-C-OH
R-CH2-C-O CH3

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore

“The Hofmann Rearrangement”

Introduction:

 The movement of alkyl or aryl groups etc. that involves the migration to carbon
atom, either cation or electron deficient (carbene).
 Like carbon, nitrogen can easily be made electron deficient, R2N** or RN
 Hence, it is expected to facilitate migration to itself as it is observed in R 3C+ of
R2C**
 E.g. Hofmann Rearrangement

General Reaction:

Conversion of an amide to an amine containing 1 carbon less by the action of

alkaline hypobromite BrO-

Treatment of amides with bromine in basic solution gives an amine with loss
of the carbonyl carbon in the form of carbon dioxide.

Examples:

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Mechanism of Rearrangement:

The reaction of bromine with sodium hydroxide forms sodium hypobromite in

situ, which transforms the primary amide into an intermediate isocyanate. The
formation of an intermediate nitrene is not possible because it implies also the
formation of an hydroxamic acid as a byproduct, which has never been observed.
The intermediate isocyanate is hydrolyzed to a primary amine, giving off carbon
dioxide.

Note:

Applications:

 Aliphatic & Aromatic amides are converted into aliphatic and aromatic amines,
respectively
 In the preparations of anthranilic acid from phthalimide
 Nicotinic acid is converted into 3-Amino pyridine
 The Symmetrical structure of α-phenyl propanamide does not change after
Hofmann reaction.

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore

“Beckmann Rearrangement”
Oximes:
Compounds, containing the grouping C = N-OH, derived from aldehydes and
ketones by condensing them with hydroxylamine are called as oximes.

+
H
R2CO + NH2OH R2C=NOH

Types of Oximes:
Oximes are of two types:

 Aldoxime: combination of aldehydes with hydroxylamine.

 Ketoxime: Combination of ketones with hydroxylamine.

RCHO + RHC=NOH
H
+ NH2OH

R2CO R2C=NOH

Chemical Properties:

 The ketoximes by the action of acids undergo a peculiar intramolecular re-

arrangement known as the BECKMAN REARRANGEMENT yielding an acid-
amide or anilide as a final product. OH HO
 Named: German Chemist Ernst Beckmann N N

Isomers: R R' R R'

If we use aldehydes or asymmetrical ketones, there is the possibility of getting

TWO STEREOISOMERS of the oximes.

Possible Isomers:

2, p-bromophenyl ethyloxime is an asymmetric oxime, hence two possible

products. OH HO
N N

CH 3 CH 3

Br Br
Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Definition:

It is an acid-catalyzed rearrangement of an oxime to an N substituted amide.

R1R2C == N - OH R2- CO - NR1

OR
R1- CO - NR2

 Open Chain oxime gives an open chain amide

 Cyclic oximes give lactam

 The Beckmann solution, acetic acid, hydrochloric acid and acetic anhydride, is
widely used to catalyze the rearrangement
 Other acids, such as polyphosphoric acid, sulfuric acid or phosphorous
pentachloride can also be used

Mechanism:
The reaction mechanism of the Beckmann rearrangement is generally
believed to consist of:

1. An alkyl migration (trans to –OH) with expulsion of the hydroxyl group to

form a nitrilium ion R1 R2 R2
OH
2. Followed by hydrolysis
C C

N N

OH R1

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Beckman Rearrangement Mechanism (In the presence of acid
chlorides/acid halides):
R1 R2 R1 R2

C RCOCl C

N N

OH OCl
-OCl-
R2
R1 R2
+C
C
N
N+
R1
H2O

+ OH R2
OH2 R2

C
C -H+
R2CO N H R1
N
N
R1
R1

Cyclic Oxime:

Muhammad Muneeb
D16M137
University College of Pharmacy,
University of the Punjab, Lahore
Beckman Rearrangement Mechanism In the presence of strong acids:
R1 R2 R1 R2

C H+ C

N N

OH OH2+
-H2O
R2
R1 R2
+C
C
N
N+
R1
H2O

+ OH R2
OH2 R2

C
C -H+
R2CO N H R1
N
N
R1
R1

Application:

 Amides can also be prepared from the Beckmann Rearrangement because it is

an acid catalyzed rearrangement of an oxime to an amide.
 An industrial synthesis of paracetamol developed by Hoechst-Celanese
involves the conversion of ketone to a ketoxime with hydroxylamine.

Muhammad Muneeb
D16M137