22.7 Retrosynthesis with Amines | Organic Chemistry
TLDRThe video script is a comprehensive lesson on the topic of retrosynthesis with amines, a crucial aspect of organic chemistry. The instructor guides viewers through the process of retrosynthesis, emphasizing the importance of considering all the reactions at one's disposal. The lesson covers multiple examples, illustrating different synthetic pathways to amines, including primary, secondary, and tertiary amines. Key reactions such as reductive amination, Gabriel synthesis, and the Sandmeyer reaction are discussed, along with strategies for identifying the most efficient synthetic routes. The instructor also highlights the use of various reagents like lithium aluminum hydride, sodium cyanoborohydride, and NBS in the synthesis process. The lesson concludes with a challenging example involving nitrobenzene, demonstrating a forward approach to synthesis when the conventional backward approach is not straightforward. The script is part of a larger organic chemistry playlist, with the instructor hinting at future content on carbohydrates and biochemistry.
Takeaways
- 🧪 Retrosynthesis is a method used in organic chemistry to work backward from a target molecule to simpler precursors.
- 📚 This lesson is part of a comprehensive organic chemistry course covering various functional groups including amines.
- 🔍 When synthesizing amines, consider all possible reactions and pathways, as there are often multiple ways to achieve the desired product.
- ⚙️ Primary amines can be synthesized through reduction of nitriles, azides, or amides, typically using lithium aluminum hydride.
- 🌟 Gabriel synthesis is another method to create primary amines, starting with an alkyl halide and phthalimide.
- ⛓ The first carbon-carbon bond made in organic chemistry is often through an SN2 reaction involving cyanide.
- 🔑 NBS (N-Bromosuccinimide) is a reagent used for specific bromination at benzylic or allylic positions.
- ⏳ Reductive amination is a common method to increase the substitution of an amine by one degree, converting a secondary amine to a tertiary amine.
- 🧩 In the context of amines, it's crucial to remember the various reactions and mechanisms learned throughout the course when approaching retrosynthesis.
- 🚫 There is no direct 'denitration' reaction for nitro groups; instead, they are typically reduced to amino groups.
- 🔄 Sandmeyer reactions involve the conversion of an aromatic amine group into a hydrogen through diazonium salts and subsequent replacement with a hydrogen using H3PO2.
- 📈 The lesson emphasizes the importance of considering the sequence of reactions and the strategic use of different reagents in achieving the target molecule.
Q & A
What is the main topic of this lesson?
-The main topic of this lesson is retrosynthesis with amines, which is the last major functional group covered in the entire organic chemistry course.
What are some common reagents used to make a primary amine?
-Some common reagents used to make a primary amine include lithium aluminum hydride (LAH) for reducing nitriles, azides, and amides.
How can you make a carbon-carbon bond using an SN2 reaction?
-A carbon-carbon bond can be made using an SN2 reaction by involving cyanide, where a good leaving group is needed, and sodium cyanide can be added in a polar aprotic solvent like DMSO or acetone.
What is the role of NBS in the synthesis?
-NBS (N-Bromosuccinimide) is used to specifically brominate benzylically or allylically, which is useful for adding bromine to the benzylic position without the need for a catalyst.
What is the general approach to retrosynthesis?
-The general approach to retrosynthesis is to work backward from the target molecule, considering all the different reactions that could lead to the formation of the various functional groups and carbon-carbon bonds.
What is reductive amination and how is it used in synthesis?
-Reductive amination is a reaction that converts a ketone or aldehyde to an amine by reacting it with an amine in the presence of a reducing agent like sodium cyanoborohydride or catalytic hydrogenation.
How can you convert an amide to an amine?
-An amide can be converted to an amine through a Hoffmann rearrangement using reagents like sodium hypobromite (NaOBr) or Br2/H2O, which removes the carbonyl group.
What is the Sandmeyer reaction and how is it used in synthesis?
-The Sandmeyer reaction is a series of reactions that involves the conversion of an aromatic amine to an aromatic halide or a triazole. It starts with the formation of a diazonium salt, which is then converted to the desired product, such as a hydrogen, using a reagent like H3PO2.
Why is it beneficial to have multiple ways to synthesize a target molecule?
-Having multiple ways to synthesize a target molecule allows chemists to choose the most efficient and practical route, considering factors like cost, availability of starting materials, reaction conditions, and the number of steps involved.
What is the significance of the amine group in directing the bromination of benzene?
-The amine group is a strong electron-donating group and acts as an ortho-para director. This means that when bromination occurs, the bromines are more likely to be placed in the ortho and para positions relative to the amine group.
How does the synthesis of amides relate to the synthesis of carboxylic acids?
-Amides can be synthesized from carboxylic acids through nucleophilic acyl substitution reactions. The carboxylic acid is first converted to an acid chloride using reagents like SOCl2, and then reacted with an amine to form the amide.
What is the first carbon-carbon bond-making reaction you learned in organic chemistry?
-The first carbon-carbon bond-making reaction typically learned is the SN2 reaction involving cyanide, where a carbon-carbon bond is formed between cyanide and an alkyl halide.
Outlines
🧪 Amine Retrosynthesis Strategies
This paragraph introduces the topic of amine retrosynthesis, emphasizing it as the final major function in the organic chemistry course. The speaker discusses various methods to synthesize amines, including reduction of nitriles, azides, and amides using lithium aluminum hydride, as well as the Gabriel synthesis starting from an alkyl halide. The focus is on identifying the most straightforward synthetic route, considering the formation of a carbon-carbon bond via an SN2 reaction involving cyanide and subsequent bromination using NBS. The paragraph concludes with a simplified three-step synthesis strategy.
🧩 Building Amines and Carbon Frameworks
The second paragraph delves into the synthesis of amides and the extension of carbon chains. It outlines the use of nucleophilic acyl substitution with acid chlorides to form amides and the creation of carboxylic acids with an additional carbon through Grignard addition to carbon dioxide or hydrolysis of nitriles. The paragraph highlights the most efficient synthetic route through the nitrile reduction and the formation of the necessary ketone via oxidation of an alkene, resulting in a concise three-step synthesis.
🔄 Amide Conversion to Secondary Amines
This section addresses the conversion of an amide to an amine while detailing the loss of the carbonyl group through the Hoffmann rearrangement using sodium hypobromite or bromine and hydroxide. It then explores the transformation of a primary amine into a secondary amine via reductive amination, identifying the need for a ketone intermediate. The paragraph simplifies the synthesis to a two-step process, emphasizing the strategic use of reductive amination and the importance of the amine's directing effects in the final product.
⚙️ Nitrobenzene to Aniline: Diazotization and Reduction
The final paragraph tackles the synthesis starting from nitrobenzene, aiming to introduce three bromines and remove the nitro group. It explains that the nitro group can be reduced to an amine group, which can then undergo various reactions, including conversion to a hydrogen atom via diazotization and subsequent treatment with hypophosphorous acid. The paragraph outlines a forward synthesis approach, highlighting the importance of adding bromines before removing the amino group to ensure the correct substitution pattern, and concludes with the conversion of the diazonium salt to the final product using H3PO2.
Mindmap
Keywords
💡Retrosynthesis
💡Amines
💡Lithium Aluminum Hydride (LiAlH4)
💡Gabriel Synthesis
💡SN2 Reaction
💡Reductive Amination
💡Hoffman Rearrangement
💡Sandmeyer Reaction
💡NBS (N-Bromosuccinimide)
💡Azide Reduction
💡Acyl Chloride
Highlights
The lesson covers the last major functional group in an organic chemistry course: amines.
Retrosynthesis can be daunting due to the variety of reactions available, but the lesson provides a structured approach through examples.
Different methods for synthesizing amines are discussed, including reduction of nitriles, azides, and amides with lithium aluminum hydride.
Gabriel synthesis is introduced as a potential method for creating primary amines.
The importance of considering the easiest routes for synthesis is emphasized, especially in the context of carbon-carbon bond formation.
SN2 reactions involving cyanide are highlighted as the first carbon-carbon bond forming reactions students learn.
The use of NBS and light or peroxide for specific bromination of benzylic positions is discussed.
A three-step synthesis for creating the target amine is presented as the most obvious and straightforward method.
Alternative synthesis routes are considered and compared for efficiency and practicality.
Reductive amination is identified as a common method for increasing the substitution degree of amines.
The synthesis of a ketone from an alkene through oxidation is outlined, followed by a hydration step.
The Hoffmann rearrangement is mentioned as a method to lose a carbonyl group from an amide.
The conversion of a nitro group to an amine group and subsequent bromination to achieve the desired product is detailed.
Sandmeyer reactions are discussed for converting diazonium salts into other functional groups, including hydrogen.
The lesson emphasizes the strategic planning required in retrosynthesis, sometimes requiring a forward approach when backward synthesis is challenging.
Aniline is highlighted as a key intermediate in the synthesis involving nitrobenzene.
The lesson concludes with a reminder of the importance of considering all reactions learned throughout the course for effective retrosynthesis.
The instructor provides resources for further study, including a study guide, practice problems, and a premium course.
Transcripts
Browse More Related Video
22.3 Synthesis of Amines | Organic Chemistry
20.12 Retrosynthesis with Carboxylic Acids Derivatives | Organic Chemistry
19.9 Retrosynthesis with Aldehydes and Ketones | Organic Chemistry
12.3 Synthesis of Alcohols | Organic Chemistry
Imine and Enamine Formation Reactions With Reductive Amination
Amines: Crash Course Organic Chemistry #46
5.0 / 5 (0 votes)
Thanks for rating: