This document discusses click chemistry, which provides a method for accelerating drug discovery. Click chemistry utilizes a few practical and reliable reactions, such as the Hüisgen 1,3-dipolar cycloaddition of azides and alkynes, which produces triazole rings in high chemical yields with few byproducts. Click chemistry reactions are simple, have readily available starting materials, produce specific products, and can be conducted in water or easily removable solvents, making it useful for drug synthesis.

1. Fatima Shahid
(292401)
Mphil Pharmaceutical
Chemistry

2. BACKGROUND
 The traditional process of drug discovery based on
natural secondary metabolites has often been slow,
costly, and labor-intensive.
 Even with the advent of combinatorial chemistry
and high-throughput screening in the past two
decades, the generation of leads is dependent on
the reliability of the individual reactions to construct
the new molecular framework.

3. INTRODUCTION
 "Click Chemistry" is a term that was introduced by
K. B. Sharpless in 2001 to describe reactions that
are high yielding, wide in scope, create only
byproducts that can be removed without
chromatography, are stereospecific, simple to
perform, and can be conducted in easily removable
or benign solvents.

4. INTRO….
 Click chemistry is a newer approach to the synthesis of
drug-like molecules that can accelerate the drug
discovery process by utilizing a few practical and reliable
reactions.

5. INTRO....
 In general, the definition of click chemistry is
described as follows:
 1. give very high chemical yields of desired
products
 2. combination of readily available simple building
blocks
 3. generate almost no byproducts
 4. simple product isolation by non-chromatographic
methods
 5. reaction proceeds in water, as well as in organic
solvents

6. EXAMPLE
 While there are a number of reactions that fulfill this
criteria.
 Hüisgen 1,3-dipolar [3 + 2] cycloaddition1) of
azides and alkynes has emerged as the
frontrunner. In general, the 1,2,3-triazole ring is not
almost oxidized or reduced, which makes it
possible to strongly connect two substrates.

7. In the Hüisgen reaction, metal catalysts, such as copper
sulfate, are generally required for reaction acceleration. In
especial, it has been reported that the combination of tris[(1-
benzyl-1H-1,2,3- triazol-4-yl)methyl]amine (TBTA) [T2993]
and catalysts shows excellent reactivity

8. CLICK CHEMISTRY REACTION PROCESSES
Simple to perform
Modular
Wide in scope
High yielding
Stereospecific

9. CLICK CHEMISTRY REACTION CHARACTERISTICS
Simple reaction conditions
Readily and easily available starting materials and reagents
Use of no solvent, a benign solvent (such as water), or one
that is easily removed
Simple product isolation
Product should be stable under physiological conditions

10.  Click chemistry provides a route for the synthesis of
several heterocyclic scaffolds, amino acids,
triazole-fused heterocycles, peptides, and
chromophores

11. CLASSIFICATION OF CLICK REACTIONS
1. Cycloaddition
 These especially refer to 1,3-dipolar
cycloadditions, but also include hetero-Diels-Alder
cycloadditions

12. 2. Nucleophilic ring-openings
 These refer to the openings of strained heterocyclic
electrophiles, such as aziridines, epoxides, cyclic
sulfates, aziridinium ions, episulfonium ions, etc.

13. 3. Non-aldol carbonyl chemistry
 Examples include the formations of ureas, thioureas,
hydrazones, oxime ethers, amides, aromatic
heterocycles, etc.
 Carbonyl reactions of the aldol type generally have low
thermodynamic driving forces, hence they have longer
reaction times and produce side products, and therefore
cannot be considered click reactions.

15. 4. Additions to carbon-carbon
multiple bonds
 Examples include epoxidations, aziridinations,
dihydroxylations, sulfenyl halide additions, nitrosyl halide
additions, and certain Michael additions.

16. REFERENCES
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562
613/
 https://www.tcichemicals.com/assets/brochure-
pdfs/Brochure_R5106_E.pdf
 https://www.sigmaaldrich.com/PK/en/technical-
documents/technical-article/chemistry-and-
synthesis/adc-and-bioconjugation/click-chemistry