Click Chemistry in Action: The Chemistry Behind the 2022 Nobel Prize

Summary

In this video, the presenter explains the chemistry behind this year's Nobel Prize awarded for Click Chemistry. The reaction, which combines an alkyne and azide under copper catalysis, is efficient, simple, and happens at room temperature with high yields. The video walks through the preparation of an organic azide, the click reaction, and the purification process involving extraction, vacuum distillation, and column chromatography. Despite facing challenges with solubility and low yield in this specific case, the process remains significant for the development of pharmaceuticals and new materials, demonstrating the power of Click Chemistry in action.

Takeaways

• 😀 Click Chemistry, awarded the Nobel Prize this year, is based on a reaction between an alkine and an azide under a copper catalyst to form a 1,4-disubstituted triazole.
• 😀 The reaction is called 'Click' Chemistry due to its simplicity, occurring at room temperature, in air, and with high yields.
• 😀 Click Chemistry has significant applications in the development of pharmaceuticals and new materials.
• 😀 The experiment begins with the preparation of an organic azide by reacting TSO chloride with sodium azide to form TSO azide.
• 😀 The azide is purified by evaporating acetone under vacuum and separating it from the reaction mixture using a separatory funnel.
• 😀 After obtaining the TSO azide, the speaker prepares for the Click Chemistry reaction by dissolving the azide in acetonitrile and adding ethanal benzene, two-amino phenol, and copper acetate monohydrate.
• 😀 Copper acetate monohydrate serves as the catalyst, and the two-amino phenol reduces copper(II) to copper(I), facilitating the reaction.
• 😀 TLC analysis confirms that the azide is completely consumed, indicating the reaction is finished.
• 😀 The product is extracted using DCM and ammonium chloride, then purified by short-path vacuum distillation and column chromatography.
• 😀 Despite challenges in column chromatography due to the poor solubility of the product in the eluent, the final product is obtained with a 20% yield.
• 😀 The video concludes by emphasizing that while Click Chemistry is simple and effective for building large molecules, the specific product in this demonstration presented some challenges in purification.

Q & A

What is Click Chemistry, and why is it called that?

Click Chemistry is a reaction that occurs between an alkine and an azide under the influence of a copper catalyst, forming a 1,4-die substituted triazole. It is called 'Click Chemistry' because the reaction happens easily at room temperature, in air, and at high yields, making it as simple as 'clicking' two molecules together.

How do the Nobel Prize winners contribute to Click Chemistry?

The Nobel Prize winners independently developed the Click Chemistry reaction, which has revolutionized the synthesis of pharmaceuticals and materials by offering a simple and efficient method to connect molecules.

Why is Click Chemistry especially important for the development of pharmaceuticals?

Click Chemistry is important for pharmaceuticals because it allows for high-yield, efficient, and reproducible synthesis of complex molecules, which is essential in drug development and material design.

What are the steps involved in preparing the organic azide for the Click Chemistry reaction?

To prepare the organic azide, the reaction begins by dissolving TSO chloride in acetone and water, followed by adding sodium azide. The mixture is stirred for several hours, then the acetone is evaporated, and the product is purified using separatory funnels and ether extraction.

What role does copper acetate play in the Click Chemistry reaction?

Copper acetate acts as a catalyst in the Click Chemistry reaction. It facilitates the reaction by converting copper(II) to copper(I) in the presence of the reducing agent, two-amino phenol, enabling the coupling of the azide and alkyne to form the desired product.

What is the purpose of the TLC (Thin Layer Chromatography) in the experiment?

TLC is used to monitor the progress of the reaction. It helps verify that all the azide has been consumed by comparing the spots of the starting material (azide) and the product on the chromatogram, ensuring that the reaction has been completed.

What was the issue encountered during column chromatography, and why did it occur?

The issue with column chromatography was that the product was poorly soluble in the solvent mixture used. This caused the product to stick to the sides of the column, requiring an excessive amount of solvent to move it through the column, which resulted in inefficiency and a prolonged process.

What is the significance of the reaction's high yield in literature compared to the experimental yield in this video?

The reaction in literature is reported to have high yields, but in this experiment, the yield was lower due to practical challenges, such as the time-consuming column chromatography. This highlights the difficulty of reproducibility in experiments when all details aren't explicitly shared in literature.

Why was the final product purified by crystallization and filtration?

The final product was purified through crystallization to remove impurities. The presence of yellow impurities was detected, so the product was washed with acetone and filtered to isolate the pure compound.

How can the efficiency of Click Chemistry be improved for better reproducibility?

The efficiency of Click Chemistry can be improved by optimizing the solubility of reactants and the reaction conditions, ensuring better reproducibility. Additionally, providing more detailed procedural information in scientific literature could help others avoid the same pitfalls during experiments.