Organic chemistry, 3rd.

class
Dr. Munera Yousif

Rearrangements
In a rearrangement reaction a group moves from one atom to another in the same molecule. Most are
migrations from an atom to an adjacent one (called 1,2-shifts), but some are over longer distances.

The migrating group (W) may move with its electron pair (these can be called nucleophilic or
anionotropic rearrangements; the migrating group can be regarded as a nucleophile), without its
electron pair (electrophilic or cationotropic rearrangements; in the case of migrating hydrogen,
prototropic rearrangements), or with just one electron (free-radical rearrangements).

In any rearrangement, we can in principle distinguish between two possible modes of reaction: In
one of these, the group W becomes completely in the other W goes from A to B in the same molecule
(intramolecularrearrangement), detached from A and may end up on the B atom of a different
molecule (intermolecular rearrangement).

Nucleophilic Rearrangements
Since the migrating group carries the electron pair with it, the migration terminus B must be an atom
with only six electrons in its outer shell:

such rearrangements occure with carbocation and consist of three steps:

1) Formation of a Carbocation, the most common methods when a rearrangement is desired is the
acid treatment of an alcohol to give a carbocation from an intermediate oxonium ion:

2) Actual migration is the second step.

3) Give the final product.

Carbocations usually rearrange to more stable carbocations. Thus the direction of rearrangement is
usually, primary → secondary → tertiary.

Free-Radical Rearrangements
1
Organic chemistry, [Link]
Dr. Munera Yousif

1,2-Free-radical rearrangements are much less common than the nucleophilic type previously
considered,. Where they do occur, the general pattern is similar. There must first be generation of a
free radical, and then the actual migration in which the migrating group moves with one electron:

Finally, the new free radical must stabilize itself by a further reaction.

Electrophilic Rearrangements
Rearrangements in which a group migrates without its electrons are much rarer than the two kinds
previously considered, but the general principles are the same. A carbanion (or other negative ion) is
created first, and the actual rearrangement step involves migration of a group without its electrons:

The product of the rearrangement may be stable or may react further, depending on its nature. Such
rearrangements occure with carbanions.

Rearrangement of carbonium ions

Carbonium ions, we know, can rearrange through migration of an organic group or a hydrogen atom,
with its pair of electrons, to the electron-deficient carbon:

Loss of water from the protonated alcohol gives the n-butyl carbonium ion which can rearrange to
form a more stable carbonium ion, sec-butyl cation, which loses a hydrogen ion to give 2-butene:

2
Organic chemistry, [Link]
Dr. Munera Yousif

A migration of hydrogen with apair of electrons and the migrating group moves from one atom to the
very next atom is known as 1,2- hydride shift :

Pinacol rearrangement
Such rearrangment,the alkyl group is migrating with apair of electrones to carbocation and known
as 1,2-alkyl shift. Upon treatment with mineral acids, 2,3-dimethyl-2,3-butanediol (often called
pinacol) is converted into methyl tert-butyl ketone (often called pinacolone):

The glycol undergoes dehydration, and in such a way that rearrangement of the carbon skeleton
occurs. The pinacol rearrangement is believed to involve two important steps: (1) loss of water from
the protonated glycol to form a carbonium iori; and (2) rearrangement of the carbonium ion by 1,2-
shift to yield the protonated ketone:

When the groups attached to the carbon atoms bearing OH differ from one another, the pinacol
rearrangement can conceivably give rise to more than one compound. The product actually obtained
is determined (a) by which OH group is lost in step (1), and then (b) by which group migrates in step

3
Organic chemistry, [Link]
Dr. Munera Yousif

(2) to the electrondeficient carbon thus formed. For example, the rearrangement of l-phenyl-l,2-
propanediol. The structure of the product actually obtained, methyl benzyl ketone, indicates that the
benzyl carbonium ion (I) is formed in preference to the secondary carbonium ion (II), and that H
migrates in preference to-CH3 :

Migration takes place according to the sequence Ar > R. Hydrogen can migrate, too, but we cannot
predict its relative migratory aptitude. Hydrogen may migrate in preference to R or Ar, but this is not
always the case; indeed, it sometimes happens that with a given pinacol either H or R can migrate,
depending upon experimental conditions.

Problem: Of each of the following glycols show which carbonium ion you would expect to be the
more stable :

(a) 1 ,2-propanedio (b) 2-methyl-l,2-propanediol (c) 2-methyl-3-ethyl-2,3-pentanediol

If such an amino group is located alpha to a hydroxyl group, then treatment with nitrous acid causes
a reaction closely related to the pinacol rearrangement:

Hofmann rearrangement. Migration to electron-deficient nitrogen

4
Organic chemistry, [Link]
Dr. Munera Yousif

A reaction that we encountered as a method of synthesis of amines: the Hofmann degradation of

amides:

The reaction is believed to proceed by the following steps:

Step (1) is the halogenation of an amide. This is a known reaction, an Nhaloamide being isolated.

Step (2) is the abstraction of a hydrogen ion by hydroxide ion.

Step (3) involves the separation of a halide ion, which leaves behind an electron-deficient nitrogen
atom. Step (4) the actual rearrangement occurs. Steps (3) and (4) are generally occur at the same
time.

Step (5) is the hydrolysis of an isocyanate (R N - C=O) to form an amine and carbonate ion.

Hofmann rearrangement. Intramolecular or intermolecular?

5
Organic chemistry, [Link]
Dr. Munera Yousif

does the migrating group move from one atom to another atom within the same molecule, or does it
move from one molecule to another? The Hofmann rearrangement is shown as intramolecular. How?

. The degradation of a mixture of m-deuteriobenzamide and benzamide- l5N. When they analyzed the
product with the mass spectrometer, they found only m-deuterioaniline and aniline- 15N. There was
none of the mixture of cross-products that would have been formed if a phenyl group from one
molecule had become attached to the nitrogen of another. The results show that the Hofmann
rearrangement rs intramolecular:

Rearrangement of hydroperoxides. Migration to electron-deficient oxygen

The synthesis of phenol via cumene hydroperoxide:

The rearrangement takes place, it involves 1,2-shift to electrondeficient oxygen:

6
Organic chemistry, [Link]
Dr. Munera Yousif

(step 1) The peroxide I converts into the protonated peroxide.

(step 2) loses a molecule of water to form an intermediate in which oxygen bears only six electrons. A
1,2-shift of the phenyl group from carbon to electron-deficient oxygen.

(step 3) yields the carbonium ion II .

(step 4) carbonium ion II reacts with water gives the hydroxy compound III .

(step 5) Compound III is a hemi-acetal which breaks down to give phenol and acetone.

*The rate of overall reaction is speeded up by electron-releasing substituents in migrating

aryl groups.

In cumene hydroperoxide, If, instead of phenyl, methyl were to migrate, reaction would be expected
to yield methanol and acetophenone:

Actually, phenol and acetone are formed quantitatively, showing that a phenyl group migrates much
faster than a methyl, why?

Migration of an alkyl group must involve a transition state containing pentavalent carbon (IV).
Migration of an aryl group, on the other hand, takes place via a structure of the benzenonium ion type
(V); transition state or actual intermediate, V clearly offers an easier path for migration than does IV:

7
Organic chemistry, [Link]
Dr. Munera Yousif

The hydroperoxide may contain several aryl groups, for example, when p-nitrotriphenylmethyl
hydroperoxide (VI) is treated with acid, it yields exclusively phenol and p-nitrobenzophenone (VII); as
we would have expected, phenyl migrates in preference to p-nitrophenyl.

Problem: Treatment of aliphatic hydroperoxides, RCH2O-OH and R2CHO-OH, with aqueous acid
yields aldehydes and ketones as the only organic products. What conclusion do you draw about
migratory aptitudes?

Neighboring group effects

In a rearrangement, a near-by group carries electrons to an electron-deficient satom, and then stays
there. But sometimes, it happens, a group brings electron and then goes back to where it camefrom.

8
Organic chemistry, [Link]
Dr. Munera Yousif

This gives rise to what are called neighboring group effects: Neighboring group effects involve the
same basic process as rearrangement Indeed, in many cases there is rearrangement, but it is hidden.
What we see on the surface may be this:

But what is actually happening may be this:

The neighboring group, acting as an internal nucleophile, attacks carbon at the reaction center; the
leaving group is lost, and there is formed a bridged intermediate (I), usually a cation. This undergoes
attack by an external nucleophile to yield the product. If a neighboring group is to form a bridged
cation, it must have electrons to form the extra bond. These may be unshared pairs on atoms like
sulfur, nitrogen, oxygen, or bromine; * electrons of a double bond or aromatic ring:

When treated with concentrated hydrobromic acid, the bromohydrin 3-bromo-2-butanol is

converted into 2,3-dibromobutane. This is simply nucleophilic attack (SN 1 or SN2) by bromide ion on
the protonated alcohol. But in 1939 Winstein and Howard described the stereochemistry of this
reaction and, in doing this, opened the door to a whole new concept in organic chemistry: the
neighboring group effect:

In step (1) the protonated bromohydrin loses water to yield, not the open carbonium ion, but a
bridged bromonium ion. In step (2) bromide ion attacks this bromonium ion to give the dibromide. But
it can attack the bromonium ion at either of two carbon atoms: attack at one gives the product with
retention at both chiral centers; attack at the other gives the product with inversion about both
centers:

9
Organic chemistry, [Link]
Dr. Munera Yousif

10