Presentation on pharmaceutical and synthetic application of Hofmann reactions.

Hofmann reactions are too much important reactions in pharmaceutical chemistry. Here we tried to give some information about these reactions.

1. A PresentAtion on
PhArmAceuticAl And synthetic
APPlicAtions of hofmAnn reAction
Submitted by:
Arabindu kha
Roll no: 121112 &
MD. Sohanur
Rahaman
Roll no: 121113

2. Hofmann degradation: The Hofmann degradation is the organic reaction of a
primary amide to a primary amine with one fewer carbon atoms. This reaction is also
sometimes called the Hofmann rearrangement reaction.
Hofmann Reactions
Hofmann elimination: Hofmann elimination, also known as exhaustive
methylation, is a process where an amine is reacted to create a tertiary amine and
an alkene by treatment with excess methyl iodide followed by treatment with
silver oxide, water, and heat.

3. Applications of Hofmann reactions
:
Pharmaceutical uses:
Anthranilic acid is used to produce-
Saccharin, a sweetening agent
Loop diuretics such as furosemide
 Outlawed euphoric sedative drug methaqualone
Benzene and its derivatives.
It is the precursor of tryptophan.
Synthesis of anthranilic acid from sodium salt of phthalamic
acid by Hofmann rearrangement reaction

4. Anthranilic acid derivatives are used to inhibit the formation of
advanced glycation end products to reduce complications in diabetes.
Other uses:
In preparing perfumes to imitate jasmine and orange.
An intermediate in the production of azo dyes.
Corrosion inhibitors for metals .
Mold inhibitors in soya sauce.
Anthranilate esters could be efficient insect repellents.
Preparation of indigo from anthranilic acid.

5. Synthesis of 3-Aminopyridine from
nicotinamide by Hofmann degradation:
Pharmaceutical uses: 3- Amino pyridine is used as-
Pharmaceutical intermediates
Intermediate of colorant.
In the menufacturing of Piroxicam , Tenoxicam, and
Ampiroxicam.
In the synthesis of organic ligand 3-pyridylnicotinamide.

6. Other uses:
An intermediate for agrochemicals.
As chelate ligands to form a complex with a transition metal ion.
Aminopyridine is used as a monomer for polymerization.
3-Aminopyridines are involved in photosensitizer chemistry, luminescent
materials, metal complex chemistry and liquid crystal.
Precautions:
3-Aminopyridine can easily be absorbed through the skin. It is fatal if swallowed or
absorbed through the skin. High concentrations can be extremely destructive to the
tissues of mucous membranes and upper respiratory tract eyes and skin. Symptoms
may also include convulsions and death. It also causes damage to the nervous
system. Thermal decomposition leads to evolution of toxic gases such as carbon
monoxide and oxides of nitrogen.

7. Synthesis of 4-Aminopyridine from pyridine-4-
carboxamide via the Hofmann rearrangement.
Pharmaceutical uses: There are various applications of 4-Aminopyridine in
pharmacy such as,
as a precursor to the drug pinacidil, which affects potassium ion channels.
In the laboratory, 4-AP is a useful pharmacological tool in studying various
potassium conductance in physiology and biophysics.
NaOCl

8. At very low concentration it selectively and reversibly inhibits Shaker
channels without significant effect on other sodium, calcium, and potassium
conductance.
As a drug, to manage some of the symptoms of multiple sclerosis, and is
indicated for symptomatic improvement of walking in adults with several
variations of the disease.
4-Aminopyridine is a potent convulsant and is used to generate seizures in
animal models for the evaluation of antiseizure agents.
Clinically used in Lambert-Eaton myasthenic syndrome and multiple
sclerosis.
To improve visual function and motor skills and relieve fatigue in patients
with multiple sclerosis.
4-AP works as a potassium channel blocker and a potent calcium channel
activator.
Spinal cord injury patients have also seen improvement with 4-AP therapy.
As an antidote for tetrodotoxin poisoning.
Treatment of Parkinson's Disease.

9. Other uses:

4-Aminopyridine is also used in bird control bait. It causes convulsions
and, infrequently, death, depending on dosage. If the dose is sub-
lethal, the birds will recover after 4 or more hours without long-term
ill effect.

The amount of bait should be limited so that relatively few
birds are poisoned, causing the remainder of the flock to be frightened
away with a minimum of mortality. A lethal dose will usually cause
death within an hour.

10. Synthesis of drug, Phentermine, by Hofmann
degradation reaction:
Friedel-Craft’s alkylation
And acylation NaNH
2
Sodamide
Hofmann
degradation
Phentermine

11. Phenetermine is a sympathomimetic agent employed as an anorectic in
the treatment of obesity.
Dose: Usual, adult 15to 30mg at breakfast.

12. Synthesis of methyl amine from acetamide by
Hofmann degradation reaction.
CH
3
CONH
2
+Br
2
+4NaOH CH
3
NH
2
+Na
2
CO
3
+2NaBr+2H
2
O

13. Determination of alkaloid structure by Hofmann
reaction:
The Hofmann degradation has been a useful tool in structure determination of
alkaloids. The correct structure of lobelia alkaloids, of which lobelanine is typical,
was first deduced from the Hofmann degradations of the quaternary hydroxide.
Figure: Structure of lobelanine

14. Physiological importance of Hofmann
elimination reaction:
The design of atracurium, a neuromuscular-blocking drug or
skeletal muscle relaxant was based on the structure of
tubocurarine and suxamethomum but superior to both because
of its lack of cardiac side effects and self destruction
mechanism into blood by Hofmann elimination reaction.
Figure: Hofmann elimination of Atracurium.

15. References
1.Chemistry of Natural Products, S.V. Bhat, B.A.
Nagasampagi, M. Sivakumar.
2.Medicinal Chemistry, Ashutosh kar.
3.An Introduction to Medicinal Chemistry, Graham L. Patrick.
4.Organic Chemistry, Stereochemistry and The Chemical
natural Products, I.L. Finar.
5.www.wikipedia.com