Lec-6,7

Mechanism of Hofmann Rearrangement

Uses
Industrially, anthranilic acid is used as an intermediate for production of dyes, pigments, and
saccharin. It and its esters are used in preparing perfumes to imitate jasmine.

Synthesis of phthalimide and then anthranilic acid

Pinacol rearrangement
The pinacol rearrangement is the acid-catalyzed dehydration of glycols, which converts the glycol into an aldehyde or
a ketone.

Glycols are alcohols with two OH groups on adjacent carbon atoms

Methyl tert-butyl ketone is formed (pinacolone)

Use of Pinacolone (3,3-dimethyl-2-butanone) is an important ketone in organic chemistry. It has an
odour reminiscent of peppermint and was discovered in 1866. Its primary use is in the synthesis of
triazolylpinacolone in the synthesis of the fungicide triadimefon and in synthesis of the herbicide
metribuzin.

Pinacol rearrangement is regioselective; the major or only product is derived from the rearrangement of the
more stable carbocation.
eg:

mechanism:
Diels-Alder Reaction (Nobel Prize in 1950)
 The Diels-Alder reaction is a conjugate addition reaction of a conjugated diene to an alkene
(the dienophile).
 The simplest example is the reaction of 1,3-butadiene with ethene to form cyclohexene:

Diene dienophile cyclic compound

Diene: an unsaturated hydrocarbon containing two double bonds between carbon atoms.

Dienophile : A compound that readily reacts with a diene; especially an alkene in the Diels-Alder reaction.

Diels-Alder reaction is favoured by electron withdrawing groups on the dienophile and by electron donating
groups on the diene.

electron withdrawing groups on the dienophile like: Examples of electron releasing groups are
o Nitro groups (-NO )2

o Aldehydes (-CHO)  alkyl groups;

 alcohol groups;
o Ketones (-C=OR)  amino groups.
o Cyano groups (-CN)
o Carboxylic acid (-COOH)
o Esters (-COOR)

Halogens are also electron-withdrawing

 Since the reaction forms a cyclic product, via a cyclic transition state, it can also be described
as a "cycloaddition".
 The reaction is a concerted process:

 The analogous reaction of 1,3-butadiene with ethyne to form 1,4-cyclohexadiene is also

known:
  Due to the high degree of regio- and stereoselectivity (due to the concerted mechanism), the
Diels-Alder reaction is a very powerful reaction and is widely used in synthetic organic
chemistry.
 The reaction usually thermodynamically favourable due to the conversion of 2 π-bonds into 2
new stronger σ-bonds.
 The two reactions shown above require harsh reaction conditions, but the normal Diels-Alder
reaction is favoured by electron withdrawing groups on the electrophilic dienophile and by
electron donating groups on the nucleophilic diene.

Examples of electron withdrawing groups are

 halogens (F, Cl);

 nitriles CN;
 carbonyls RCOR';
 nitro groups NO2.

An electron releasing group or ERG (may also be called electron donating groups or EDG's) releases electrons into
a reaction center and as such stabilizes electron deficient carbocations.

Examples of electron releasing groups are

 alkyl groups;
 alcohol groups;
 amino groups.

 Some common examples of the components are shown below:

Dienes
 Dienophiles

Stereoselectivity:

 The Diels-Alder reaction is stereospecific with respect to both the diene and the dienophile.
 Addition is syn on both components (bonds form from same species at the same time)
 This is illustrated by the examples below:

a cis-dienophile gives cis-substituents in the product.

a trans-dienophile gives trans-substituents in the product

1. Stereochemistry In The Diels-Alder: A Tale of Two Dienophiles (cis– and trans-)

A pi bond is broken on the dienophile during the course of the Diels-Alder reaction, and the hybridization goes from
sp2 to sp3. So what happens to the stereochemistry of the groups attached the pi bond?

Take the two dienophiles maleic acid and fumaric acid for example. These two molecules are diastereomers, differing
only in the orientation of the two carboxylic acid groups about the double bond.

Diastereomers are defined as compounds which have the same molecular formula and sequence of bonded elements
but which are nonsuperimposable, non-mirror images.

1. Stereochemistry In the Diels-Alder: A Tale of Two Dienophiles (cis– and trans-)

A pi bond is broken on the dienophile during the course of the Diels-Alder reaction, and the hybridization goes from
sp2 to sp3. So what happens to the stereochemistry of the groups attached the pi bond?

Take the two dienophiles maleic acid and fumaric acid for example. These two molecules are diastereomers, differing
only in the orientation of the two carboxylic acid groups about the double bond.
2. The Relationship Of The Substitutents About The Double Bond In The Dienophile Is
Preserved In The Diels-Alder Product

Let’s call this Diels-Alder Stereochemistry Rule #1:

cis– dienophiles give us cis- products, and trans– dienophiles give us trans- products.

What about the diene?

3. Stereochemistry of The Diene Substituents In The Diels-Alder Product: “Outside” And

“Inside” Substituents

Substituents on C-2 and C-3 of the diene aren’t an issue: they start the reaction on a (flat) sp2 hybridized carbon and
end the reaction on a (flat) sp2 hybridized carbon. No chiral centers are created here, so there’s no stereochemistry
issues to concern ourselves with.

But what about the substituents on C-1 and C-4? They are on an sp2 hybridized carbon in the starting material and end
up on an sp3 hybridized carbon in the product.

Here’s what we observe from experiment:

It turns out that the two “outside groups” on the diene (labelled “A“, below) when drawn in the s-cis conformation
end up on one face of the new six-membered ring, and the two “inside” groups (labelled “B“) both end up on the
other face of the ring. Let’s call this Diels-Alder Stereochemistry Rule #2.