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

Chemiolis
17 Oct 202208:02
EducationalLearning
32 Likes 10 Comments

TLDRIn this video, the presenter delves into the chemistry behind Click Chemistry, the recipient of this year's Nobel Prize. The process involves a reaction between an alkyne and an azide, catalyzed by a copper catalyst, to form a 1,4-disubstituted triazole at room temperature and in air, hence the 'click' analogy. The video demonstrates the synthesis of a specific azide compound, followed by a Click reaction with ethanyl benzene, facilitated by copper(II) acetate monohydrate and 2-aminophenol. The presenter meticulously details the purification steps, including extraction, distillation, and column chromatography, highlighting the challenges faced due to the product's poor solubility. Despite a lower yield than expected, the video successfully showcases the simplicity and potential of Click Chemistry in pharmaceuticals and materials science, prompting viewers to consider its Nobel Prize worthiness.

Takeaways
  • 🧪 The Nobel Prize in Chemistry was awarded for the development of Click Chemistry, a reaction where an alkyne and an azide react to form a 1,4-disubstituted triazole in the presence of a copper catalyst.
  • 🔁 Click Chemistry is termed so because it occurs readily at room temperature, in air, and yields high, making it akin to 'clicking' two molecules together.
  • 💊 This chemistry technique is significant for the development of pharmaceuticals and new materials due to its simplicity and efficiency.
  • ⚙️ The video demonstrates the preparation of an organic acid, torso chloride, and its subsequent reaction with sodium azide to form torso azide and sodium chloride.
  • 🧊 An ice bath is used to control the reaction temperature, and the reaction is allowed to proceed for 4 hours at room temperature.
  • 🌡️ The acetone is then boiled off under vacuum, and the mixture is separated into layers using a separatory funnel.
  • 🌟 The product, torso azide, is washed with diethyl ether and then with water and a sodium carbonate solution to purify it.
  • 🧴 The azide is dried using anhydrous sodium sulfate, and the pure azide is obtained after evaporating the ether.
  • 🔄 The Click reaction is initiated by adding acetonitrile, ethanyl benzene, 2-aminophenol, and copper(II) acetate monohydrate, with the latter acting as a catalyst.
  • 📈 The progress of the reaction is monitored using thin-layer chromatography (TLC) to ensure all the azide has been consumed.
  • ⚖️ After the reaction, the catalyst is removed by dilution and extraction with ammonium chloride solution and dichloromethane (DCM).
  • 🌈 Column chromatography is used for further purification, although the product's poor solubility in the eluent presents a challenge.
  • 📊 The final yield of the product is 20%, which is lower than the high yields reported in literature, possibly due to the premature stopping of the column chromatography.
Q & A
  • What is Click Chemistry and why was it awarded the Nobel Prize?

    -Click Chemistry is a set of reactions that occur at room temperature in air and at high yields, allowing for the simple and efficient 'clicking' together of two molecules. It was awarded the Nobel Prize for its significant role in the development of pharmaceuticals and new materials, due to its simplicity and efficiency.

  • What are the reactants in the Click Chemistry reaction described in the video?

    -The reactants in the Click Chemistry reaction are an alkyne and an azide, which react under the influence of a copper catalyst to form a 1,4-disubstituted triazole.

  • What is the significance of the reaction happening at room temperature and in air?

    -The ability for the reaction to occur at room temperature and in air indicates that it is a robust and practical method. This makes it especially useful for industrial applications and research, as it does not require extreme conditions or expensive equipment.

  • What is the first step in the preparation process for the Click Chemistry reaction shown in the video?

    -The first step is to prepare an organic acid, which involves setting up a stir blade in a dish and making an ice bath. Then, 2 grams of tosyl chloride is added to a flask, followed by a stir bar, 20 ml of acetone, and 10 ml of water.

  • What is the role of sodium azide in the reaction?

    -Sodium azide provides the azide group that reacts with the alkyne. In the reaction, the chlorine from tosyl chloride is replaced by the azide group from sodium azide to form tosyl azide and sodium chloride.

  • How is the acetone removed from the reaction mixture?

    -The acetone is removed by boiling it off. The flask is set in a heating mantle, a gas adapter is attached, and the mixture is heated to 30°C. A vacuum is pulled, allowing the acetone to be drawn off through the pump.

  • What is the purpose of using a separatory funnel in the purification process?

    -A separatory funnel is used to separate the two layers of the mixture, allowing the product, which is sitting on the bottom, to be isolated. It also facilitates washing the product with different solutions to remove impurities.

  • What is the role of copper(II) acetate monohydrate in the Click Chemistry reaction?

    -Copper(II) acetate monohydrate acts as a catalyst in the Click Chemistry reaction, facilitating the coupling of tosyl azide and ethanyl benzene.

  • What is the purpose of using 2-aminophenol in the reaction?

    -2-Aminophenol serves as a reducing agent in the reaction. It converts copper(II) to copper(I), which is necessary for the catalytic cycle of the Click Chemistry reaction.

  • How is the product of the Click Chemistry reaction purified?

    -The product is purified through a series of steps including dilution with ammonium chloride solution, extraction with dichloromethane (DCM), drying with anhydrous sodium sulfate, and vacuum distillation to remove the DCM. Column chromatography is then used for further purification.

  • What is the final yield of the product in the video?

    -The final yield of the product in the video is 20%, which is lower than the high yields typically reported in the literature.

  • Why was the column chromatography step challenging in this particular Click Chemistry reaction?

    -The column chromatography step was challenging because the product was not very soluble in the eluent, requiring a large amount of solvent to get it through the column. This issue was not mentioned in the literature, which can be problematic for reproducibility.

Outlines
00:00
🧪 Nobel Prize Chemistry: Click Chemistry Explained

This paragraph introduces the chemistry behind the Nobel Prize, focusing on Click Chemistry. The speaker explains that two laureates independently developed the Click reaction, which involves an alkyne and an azide reacting under the influence of a copper catalyst to form a 1,4-disubstituted triazole. The reaction is notable for its simplicity, as it occurs at room temperature in air and yields high results, hence the 'click' moniker. The process is significant for pharmaceutical and material development. The video demonstrates how to prepare an organic acid, the synthesis of torso azide, and the subsequent steps leading up to the Click reaction itself, which includes the use of acetonitrile, ethanyl benzene, and 2-aminophenol, catalyzed by copper(II) acetate monohydrate.

05:00
🔬 Column Chromatography and Product Purification

The second paragraph details the challenges and process of purifying the product synthesized through Click chemistry. The speaker describes setting up a column with silica gel and using ethyl acetate in hexanes as the eluent. The purification process is hindered by the product's poor solubility, which was not mentioned in the literature reviewed. Despite the challenges, the product is eventually recovered through vacuum distillation and crystallization, with the final yield being lower than expected due to the time-consuming nature of the column chromatography. The speaker concludes by discussing the simplicity and effectiveness of Click chemistry and invites viewers to share their thoughts on its Nobel Prize recognition.

Mindmap
Keywords
💡Click Chemistry
Click Chemistry refers to a set of reliable, widely applicable chemical reactions that join small units together to form larger, often biologically active molecules quickly and in a modular fashion. It is a key concept in the video as it is the chemistry behind the Nobel Prize discussed. The term 'click' is used to describe the ease and efficiency of these reactions, which can occur at room temperature in the presence of air, yielding the products in a simple 'click' together of molecules.
💡Nobel Prize
The Nobel Prize is an international award administered by the Nobel Foundation, which recognizes academic and cultural achievements in various fields. In the context of the video, it is awarded for the development of Click Chemistry, highlighting its significant impact on the field of chemistry and its potential applications in pharmaceuticals and materials science.
💡Alkyne
An alkyne is a hydrocarbon with at least one carbon-carbon triple bond. In the video, alkynes play a crucial role in the Click Chemistry reaction where they react with azides under the influence of a catalyst to form a triazole ring structure. This is a fundamental aspect of the chemistry demonstrated in the video.
💡Azide
An azide is a compound containing the azido group (-N3). In the script, an azide reacts with an alkyne to perform the Click Chemistry reaction, resulting in the formation of a 1,4-disubstituted triazole. The azide is a key reactant in the process and is used to form torso azide in the preparation phase.
💡Copper Catalyst
A copper catalyst is used to facilitate the Click Chemistry reaction between an alkyne and an azide. Specifically, copper(II) acetate monohydrate acts as a catalyst in the video, enabling the reaction to proceed efficiently. The catalyst is essential for the 'clicking' of the molecules together, illustrating the role of catalysts in promoting chemical reactions.
💡Triazole
Triazole is a heterocyclic organic compound with a five-membered ring containing four nitrogen atoms. The formation of a 1,4-disubstituted triazole is the goal of the Click Chemistry reaction shown in the video. This structure is significant as it is a common component in many pharmaceuticals and materials, demonstrating the practical applications of Click Chemistry.
💡Pharmaceuticals
Pharmaceuticals are drugs or medications used in the treatment and prevention of diseases. The video mentions that Click Chemistry is particularly interesting for the development of pharmaceuticals due to its efficiency and reliability. This highlights the potential of Click Chemistry in creating complex molecules that can be used in the medical field.
💡TLC (Thin Layer Chromatography)
TLC is a widely used method in chemistry for the separation and identification of compounds in a mixture. In the video, TLC is used to confirm the completion of the Click Chemistry reaction by checking for the consumption of the azide. The absence of azide spots on the TLC plate indicates that the reaction has gone to completion.
💡Column Chromatography
Column chromatography is a technique used to separate the components of a mixture based on their different interactions with a stationary phase and a mobile phase. In the video, it is used to purify the product of the Click Chemistry reaction. The process is described as challenging due to the poor solubility of the product, which is an important consideration in the purification process.
💡Yield
Yield in chemistry refers to the amount of product obtained from a chemical reaction relative to the theoretical maximum amount that could be produced. The video concludes with the yield of the Click Chemistry reaction being 20%, which is lower than the high yields typically reported in literature. This discrepancy is attributed to the challenges faced during the column chromatography step, emphasizing the practical aspects of conducting such reactions.
💡Solubility
Solubility is the maximum amount of a substance that can dissolve in a given amount of solvent at a certain temperature. In the context of the video, the solubility of the product is a critical factor affecting the purification process. The poor solubility of the product in the eluent used for column chromatography leads to a longer and more complex purification process, which is a significant aspect of the video's narrative.
Highlights

The video discusses the chemistry behind the Nobel Prize-winning concept of Click chemistry.

Click chemistry involves a reaction where an alkyne and an azide react to form a 1,4-disubstituted triazole.

The term 'Click' refers to the simplicity and efficiency of the reaction, which occurs at room temperature, in air, and with high yields.

Click chemistry is significant for the development of pharmaceuticals and new materials.

The preparation of an organic acid is demonstrated as part of the Click reaction setup.

The use of torso chloride, acetone, and water, along with sodium azide, is shown to produce torso azide and sodium chloride.

Azide group replacement from sodium azide is highlighted as a key step in the reaction.

The process of boiling off acetone and condensing water vapors is demonstrated.

Extraction and washing of the product using diethyl ether and a sodium carbonate solution are shown.

Anhydrous sodium sulfate is used to dry the ether layer in preparation for the Click chemistry.

The azide's melting point close to room temperature is noted, and its purification through freezing is demonstrated.

Acetonitrile is used to dissolve the azide solid for the commencement of the Click reaction.

The addition of ethanyl benzene and 2-aminophenol initiates the Click reaction with copper(II) acetate monohydrate as a catalyst.

The reaction mixture's color change indicates the progress of the Click reaction.

Thin-layer chromatography (TLC) is used to confirm the completion of the reaction by checking for the consumption of azide.

The removal of the catalyst and purification of the product through extraction with ammonium chloride solution and DCM is shown.

Column chromatography is used for further purification, despite challenges due to the product's poor solubility.

The final product is obtained through vacuum distillation and washing with ethyl acetate in hexanes to remove impurities.

The yield of the product is 20%, which is lower than the high yields reported in literature, possibly due to the premature stopping of the column.

The video concludes by emphasizing the simplicity and utility of Click chemistry in building large molecules.

Transcripts
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