The document summarizes the Ugi reaction, a multi-component reaction where an amine, aldehyde or ketone, carboxylic acid, and isocyanide react to form a bis-amide product. It discusses the characteristics of the Ugi reaction, including that it is exothermic, high yielding, allows for creation of chemical libraries through varying substituents. The reaction mechanism involves initial imine formation, proton exchange, additions of the isocyanide and carboxylic acid. Applications described include syntheses of pharmaceuticals like norsufentanil analogs and quinapril hydrochloride, as well as compounds with fungicidal, larvicidal, and Alzheimer's disease treatment properties.

1. UGI REACTION
SUBMITTED TO:
PROF. DR. MATLOOB AHMAD
SUBMITTED BY:
AQSA KANWAL
PHD CHEMISTRY 1ST (2022-2025)

2. CONTENTS:
 INTRODUCTION
 CHARACTERISTICS
 GENERAL REACTION
 REACTION MECHANISM
 SYNTHETIC APPLICATIONS
 GENERAL APPLICATIONS
 REFERENCES

3. Introduction
 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 multicomponent reaction.
 Ugi reaction takes place between a ketone or aldehyde, an
amine, an isocyanide and a carboxylic acid to form a bis
amide.
 It was first reported by Prof. Ivar Karl Ugi in 1959.

4. CHARACTERISTICS:
 It is exothermic reaction.
 Usually complete in minutes after isocyanide
addition.
 This is an uncatalyzed reaction.
 Has high atom economy as only a molecule of
water is lost.
 High chemical yield.
 Changing substituents R1, R2, R3, R4 and R5 a huge
chemical libraries can be build.

5. GERENAL REACTION

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. REACTION MECHANISM

8. REACTION MECHANISM

9. REACTION MECHANISM

10. Synthesis of novel norsufentanil analogs
 Synthetic opioid analgesic used as a pain medication to
relieve pain in different treatments.

11. Synthesis of novel norsufentanil analogs
Nami, M., Salehi, P., Dabiri, M., Bararjanian, M., Gharaghani, S., Khoramjouy, M., &
Faizi, M. (2018). Synthesis of novel norsufentanil analogs via a four‐component Ugi
reaction and in vivo, docking, and QSAR studies of their analgesic
activity. Chemical Biology & Drug Design, 91(4), 902-914.

12. Synthesis of Quinapril hydrochloride
 An active pharmaceutical drug.
 Used for the treatment of Hypertension.
Borase, B. B., Godbole, H. M., Singh, G. P., Upadhyay, P. R., Trivedi, A., Bhat, V., & Shenoy, G. G. (2020).
Application of Ugi three component reaction for the synthesis of quinapril hydrochloride. Synthetic
Communications, 50(1), 48-55.

13. Synthesis of the phenylglycinamide
derivatives:
 In Crop protection chemistry, exhibits larvicidal activity against
Culex pipiens pallens (common house mosquito).

14. Synthesis of the phenylglycinamide
derivatives
 Acts as fungicides.
 Both display potent efficacy against Alternaria solani
(potato and tomato early blight).
Lamberth, C. (2020). Multicomponent reactions in crop protection chemistry. Bioorganic &
medicinal chemistry, 28(10), 115471.

15. Isoindolinone derivatives:
 Isoindolinones are an important class of heterocyclic
compounds.
 Used as building blocks for pharmaceutical active drugs and
natural products.
Varga, V., Milen, M., & Ábrányi-Balogh, P. (2018). Propylphosphonic anhydride
(T3P®) mediated synthesis of 3-oxoisoindoline-1-carboxamides from 2-
formylbenzoic acid, amines, and isocyanides. Preparation of isoindolinone
alkaloids. Tetrahedron Letters, 59(41), 3683-3689.

16. Synthesis of Oxindole−Lactam
Hybrids
 Oxindole−lactam hybrids are new potential agents for the treatment
of Alzheimer’s disease.
Brandao, P., Lopez, O., Leitzbach, L., Stark, H., Fernandez-Bolanos, J. G., Burke, A. J., &
Pineiro, M. (2021). Ugi Reaction Synthesis of Oxindole–Lactam Hybrids as Selective
Butyrylcholinesterase Inhibitors. ACS Medicinal Chemistry Letters, 12(11), 1718-1725.

17. Synthesis of pseudopeptides connected to
sulfonamides:
 Peptides connected to sulfonamide skeletons have numerous biological
properties such as antibacterial, anti-cancer, antiviral, antifungal, anti-
diabetic, antiinflammatory, protease inhibitor, diuretics, HIV-protease, anti-
epileptic drugs, cyclooxygenase-2 inhibitor, anticonvulsant.
Nazeri, M. T., Nowee, A. B., & Shaabani, A. (2021). A new one-pot synthesis of
pseudopeptide connected to sulfonamide via the tandem N-sulfonylation/Ugi
reactions. New Journal of Chemistry, 45(7), 3479-3484.

18. THANK
YOU