The document describes the Ugi reaction, a multi-component reaction where a ketone or aldehyde, amine, isocyanide, and carboxylic acid come together to form a bis-amide. It was first reported in 1959 by Ivar Karl Ugi. The reaction has high atom economy and yields, occurs rapidly at room temperature, and is uncatalyzed. It has applications in synthesizing chemical libraries and multiple compounds in one step, such as the HIV drug Crixivan. The mechanism involves imine formation, proton exchange, additions of the isocyanide and carboxylic acid, and a Mumm's rearrangement.

1. AMITY INSTITUTE OF PHARMACY
UGI REACTION
Submitted to Submitted by
Dr. Neerupma Dhiman Firuj Ahmed
Department of Pharmaceutical Chemistry Master of Pharmacy
1st Year

2. Index:
1. Introduction
2. Characteristics
3. General Reaction
4. Reaction Mechanism
5. Synthetic Applications
6. General Applications
7. Reference

3. UGI REACTION:
A multi component reaction.
Multi Component reaction: A multi component reaction are those
reaction where three or more reactants come together in a single
reaction vessel to form a new product.
It is the most studied and used multi component reaction.
Ugi reaction takes place between a ketone or aldehyde, an amine, an
isocyanides and a carboxylic acid to form a bis amide.
Reported first by prof. Ivar Karl Ugi in the year 1959.

4. CHARACTERISTICS:
1.It is exothermic reaction.
2.Usually completes in minutes after isocyanide addition.
3.This is an uncatalyzed reaction.
4.Has high atom economy as only a molecule of water is lost.
5.High chemical yield.

5. GENERAL REACTION
Carboxylic Acid Amine Ketone or Aldehyde Isocyanide
Bis -Amide

6. REACTION MECHANISM
STEPS :
1. Imine formation with amine vs ketone.
2. Proton exchange(formation of iminium ion)
3. Nucleophilic addition of isocyanide.
4. Nucleophilic addition of Carboxylic acid anion.
5. Mumm’s rearrangement.

7. Amine Ketone
1. Imine formation
Acid
Imine exchange
2. Proton exchange

8. Iminium ion
3.Nucleophilic addition of
isocyanide
Isocyanide
4.Nucleophilic addition of
carboxylic acid anion

9. Mumm’s rearrangement
5. Mumm’s
Rearrangement
Bis-Amide

10. SYNTHETIC APPLICATION OF THE UGI REACTION:
1.Synthesis of a synthetic opioid analgesic norsufentanil derivative: Fentanyl or fentanyl is a synthetic
opioid analgesic used as a pain medication to relieve pain after different treatments.
Novel substituted amino acid –tethered norsufentanil derivatives 2 were synthesized by Ugi reaction utilizing
the Carboxylic acid-tethered norsufentanil 1 with a variety of aldehydes, amines, and isocyanides to produce
a library of the desired norsufentanil derivatives compounds 2.
1 2

11. GENERAL APPLICATIONS:
1.It is used to develop chemical libraries.
2.It is used to synthesized a different number of compounds in
one reaction.
3.Crixivan(brand name for Indinavir) can be prepared by using ugi
reaction(used to treat HIV/AIDS)
4.Many of the caine-type anaesthetics are synthesized using this
reaction.
Ex– Lidocaine and Bupivacaine.

12. REFERENCE:
Boukis A.C., et al., “Multicomponent Reactions Provide Key
Molecules for Secret Communication”, Nature Communications,
2018, 9:1439.
https://www.organic-
chemistry.org/namedreactions/ugireaction.shtm
https://www.organic-reaction.com/organic-reaction/multi-
component-reactions/ugi-reaction/

13. THANK YOU