Michael Addition reaction is included in the syllabus of Advance Organic Chemistry M pharm (Pharmaceutical Chemistry) 1st semester

1. CHHATRAPATI SHAHU JI MAHARAJ UNIVERSITY
KANPUR
TOPIC- STUDY OF MICHAELADDITION REACTION
Diwakar Kumar Mishra
M PHARM 1ST YEAR
PHARMACEUTICAL CHEMISTRY
SCHOOL OF PHARMACEUTICAL SCIENCES
PRESENTED BY-

2. Topic
• Introduction
• Michael reaction
• Reaction Mechanism
• Applications

3. Definition:- Michael Addition can be defined as the nucleophilic
addition of a nucleophile (or a carbanion) to an 𝛼,𝛽-unsaturated
carbonyl compound, and it belongs to a group of reactions that are
considered very useful in the mild formation of carbon- carbon
bonds. Michael donor Michael acceptor
Enolates of carbonyl compounds will add to an α,β- unsaturated
carbonyl compounds to give dicarbonyl compounds. This is called
the Michael reaction.
INTRODUCTION

4. In this scheme, R and R' on the nucleophile (the Michael donor) represent
electron-withdrawing substituents such as acyl and cyano groups, which make the
adjacent methylene hydrogen acidic enough to form a carbanion when reacted
with the base, B:. The R" substituent on the activated alkene, also called a
Michael acceptor, is usually a ketone, Nitro groups. Michael reaction was first
defined by Arthur Michael, an American organic chemist.
MICHAEL ADDITION REACTION

5. MECHANISM

6. Michael Addition Mechanism
Step 1:- The carbonyl-containing compound is attacked by the base in the
first step of the Michael addition mechanism. Subsequently, the alpha
hydrogen of the carbonyl compound is deprotonated by the base, leading to
the formation of the carbanion (which has enolate ion).
Step 2:- The electron withdrawing groups of the carbanion give it stability.
The enolate ion and the Michael acceptor now react together, leading to the
formation of a new carbon- carbon bond. Thus, the enolate ion completes a
1,4 addition on the 𝛼,𝛽-unsaturated carbonyl compound

7. Step 3:-
The compound formed from the 1,4 addition of the enolate on the 𝛼,
𝛽-unsaturated carbonyl compound is now protonated, giving the
required product. The Michael addition mechanism is illustrated
above along with the list of bonds formed and broken during the
Michael reaction. Thus, the 1,5 dicarbonyl compound is formed from
the addition of the enolate of a carbonyl compound to an 𝛼,𝛽-
unsaturated carbonyl compound. This product is commonly referred
to as a Michael Adduct

8. A well-known Michael reaction is the synthesis of warfarin from 4- hydroxycoumarin
and benzylideneacetone It is an anticoagulant. It is commonly used to treat blood
clots such as deep vein thrombosis and pulmonary embolism, and to prevent stroke
in people who have atrial fibrillation, valvular heart disease or artificial heart valves.
Warfarin decreases blood clotting by blocking an enzyme called vitamin K epoxide
reductase that reactivates vitamin K1 Base Hydroxycoumarin Warfarin.
APPLICATION
1. Preparation of warfarin

9. 2.Formation of methyl acrylate
from diethyl malonate

10. The above-shown example is a 1,3-diketone but other electron-withdrawing
groups such as esters, nitriles and nitro compounds in the same arrangment
can also be Michael donors. Similarly, the electron-withdrawing group of
the ɑ, β- unsaturated compound can be any of these as well
3. Formation Michael Donor