20.12 Retrosynthesis with Carboxylic Acids Derivatives | Organic Chemistry
TLDRThe video script outlines a lesson on organic chemistry, specifically focusing on the process of retrosynthesis with carboxylic acids and their derivatives. The instructor guides viewers through four example problems, starting with an initial reactant and working backwards to identify the necessary reagents and intermediates to synthesize a final product. The lesson covers various methods for synthesizing carboxylic acid derivatives, such as nucleophilic acyl substitution and Fischer esterification, and emphasizes the importance of understanding the carbon skeleton and functional group transformations. The instructor also highlights the use of thionyl chloride for acid chloride synthesis and the conversion of primary alcohols to carboxylic acids through oxidation. Additionally, the script touches on the synthesis of amines from amides and nitriles using lithium aluminum hydride reduction. The lesson concludes with a reminder to subscribe for weekly updates and a promotion for the instructor's premium course on chatsprep.com.
Takeaways
- 🔍 **Retrosynthesis Process**: The script discusses the process of working backwards from a final product to determine the necessary reagents and intermediates to synthesize it.
- ⛓ **Carbon Skeleton Matching**: The importance of matching the carbon skeleton of the initial reactant and the final product is emphasized, noting no addition or removal of carbons in the examples provided.
- 🧪 **Carboxylic Acid Derivatives Synthesis**: It is highlighted that there are fewer methods to synthesize carboxylic acid derivatives compared to carboxylic acids themselves.
- 🔄 **Nucleophilic Acyl Substitution**: This method is often used for converting between different carboxylic acid derivatives, and if a carboxylic acid can be made, it can usually be converted into any derivative.
- ⚙️ **Acid Chloride Synthesis**: The only known method to make an acid chloride is from the corresponding carboxylic acid using thionyl chloride (SOCl2).
- 🍃 **Oxidation of Alcohols**: Primary alcohols can be oxidized to carboxylic acids using chromic acid (H2CrO4) or sodium dichromate in H2SO4.
- 🔬 **Grignard Reaction for C-C Bond Formation**: The script mentions the use of Grignard reactions for creating carbon-carbon bonds, which is a common method in organic chemistry.
- ⚒️ **Fischer Esterification**: An alternative method for synthesizing esters from carboxylic acids and alcohols using an acid catalyst is discussed.
- ⛏️ **Reduction of Nitriles and Amides**: Lithium aluminum hydride (LiAlH4) is used to reduce nitriles and amides to amines, which is a key method for amine synthesis.
- 🧩 **Multiple Pathways**: The script acknowledges that there are often multiple pathways to achieve a synthesis, but some are more direct or yield better results.
- 📚 **Study Resources**: The speaker provides information about study guides, practice problems, and rapid reviews available on chatsprep.com for those studying organic chemistry.
Q & A
What is the primary objective of the lesson on retrosynthesis with carboxylic acids and their derivatives?
-The primary objective is to work through example problems by starting with an initial reactant and a final product, then working backwards to identify all the necessary reagents and intermediates to transform the initial reactant into the final product.
How does the process of synthesizing carboxylic acid derivatives typically begin?
-The process typically begins with the corresponding carboxylic acid, which can then be converted into any of the derivatives through nucleophilic acyl substitution or other reactions.
What is the only method known to make an acid chloride in the context of this lesson?
-The only method known to make an acid chloride is by using the corresponding carboxylic acid and thionyl chloride (SOCl2).
Why is ozonolysis not the best choice for the first example in the script?
-Ozonolysis is not the best choice because it would result in a product with one fewer carbon than the starting material, which is not the desired outcome in the first example.
How can a primary alcohol be converted into a carboxylic acid?
-A primary alcohol can be converted into a carboxylic acid through oxidation using chromic acid (H2CrO4) or sodium dichromate in H2SO4.
What is the general strategy for making a carbon-carbon bond in the second example?
-The general strategy for making a carbon-carbon bond in the second example is to use organometallic compounds like those in a Grignard reaction.
How can an ester be synthesized from an acid chloride?
-An ester can be synthesized from an acid chloride by replacing the chloride with an ethoxy group, which can be done using a base-catalyzed reaction with an ethoxide ion or ethanol.
What is the key reaction for making a carboxylic acid with one more carbon than the starting material?
-The key reaction for making a carboxylic acid with one more carbon than the starting material is Grignard addition to carbon dioxide, followed by an acid workup step.
What is the preferred method for synthesizing an amide from a carboxylic acid derivative in the context of this lesson?
-The preferred method for synthesizing an amide is to start with the most reactive carboxylic acid derivative, specifically the acid chloride, and use ammonia to replace the chlorine, with two equivalents of ammonia used (one as a nucleophile and the other as a base).
How can one determine the most efficient synthesis route in a retrosynthesis problem?
-One can determine the most efficient synthesis route by considering the number of steps, the reactivity of the starting materials, the availability of the reagents, and the expected yields of each step.
What is the role of lithium aluminum hydride (LiAlH4) in the synthesis of amines in the context of this lesson?
-Lithium aluminum hydride (LiAlH4) is used to reduce nitriles or amides to amines, with an acid workup step to complete the reaction.
Why might a student get full credit for a synthesis route that is not the most direct or has more steps?
-A student might get full credit for a synthesis route that is not the most direct or has more steps because the route might still be valid and lead to the correct product, and the evaluation could consider the understanding of the chemistry involved rather than just the brevity of the route.
Outlines
🔍 Retrosynthesis of Carboxylic Acids and Derivatives
This paragraph introduces the concept of retrosynthesis with carboxylic acids and their derivatives. The speaker outlines a method for working backward from a final product to identify the necessary reagents and intermediates. The process involves matching carbon skeletons and considering various synthetic pathways, such as nucleophilic acyl substitution and oxidation of alcohols. The synthesis of an acid chloride from a corresponding carboxylic acid using thionyl chloride is highlighted, along with the conversion of a primary alcohol to a carboxylic acid through oxidation. The paragraph also touches on the synthesis of esters and the importance of considering the reactivity of different carboxylic acid derivatives.
🧪 Building Carboxylic Acids with an Extra Carbon
The second paragraph delves into the synthesis of a carboxylic acid with an additional carbon atom compared to the starting material. The discussion focuses on Grignard reactions, specifically the addition of a Grignard reagent to carbon dioxide, which achieves the desired outcome. The synthesis of the Grignard reagent from the corresponding halide is also covered. Alternative methods, such as base conversion to a carboxylate and subsequent reaction with ethyl bromide, are briefly mentioned. The potential for higher yields with acid chlorides in esterification reactions is discussed, along with the strategic considerations of choosing between different synthetic routes in a lab setting.
🚀 Constructing Amines from Ethylbenzene
This paragraph addresses the synthesis of an amine from ethylbenzene, with the challenge of losing a carbon during the process. The speaker explores the limited methods available for synthesizing amines, focusing on the conversion from an amide using lithium aluminum hydride. The paragraph also discusses the formation of nitriles and amides, and the strategic choice of using an acid chloride as a starting point for the synthesis. The use of thionyl chloride to create an acid chloride from a carboxylic acid is highlighted, and the paragraph concludes with a discussion on the various methods for forming a carboxylic acid, including oxidation and Grignard addition to CO2.
🛠️ Optimizing Synthesis Pathways for Efficiency
The final paragraph emphasizes the importance of selecting the most efficient synthesis pathway. It discusses the process of creating a carboxylic acid from a benzylic carbon, considering methods like chromic acid oxidation and Grignard addition to CO2. The speaker also explores alternative routes, such as forming an alkene through elimination and subsequent oxidation, but concludes that these methods would result in longer and less efficient syntheses. The paragraph concludes with a reminder of the increasing complexity of synthesis as more reactions are learned and the importance of finding the most straightforward and effective route.
Mindmap
Keywords
💡Retrosynthesis
💡Carboxylic Acids
💡Carboxylic Acid Derivatives
💡Nucleophilic Acyl Substitution
💡Acid Chloride
💡Ozonolysis
💡Oxidation of Alcohols
💡Grignard Reaction
💡Fischer Esterification
💡Amines
💡Lithium Aluminum Hydride
Highlights
Retrosynthesis involves working backward from a final product to determine the necessary reagents and intermediates.
Carboxylic acid derivatives can often be synthesized from the corresponding carboxylic acid through nucleophilic acyl substitution.
Acid chlorides are typically synthesized from carboxylic acids using thionyl chloride (SOCl2).
Primary alcohols can be oxidized to carboxylic acids using chromic acid (H2CrO4) or sodium dichromate in H2SO4.
Ozonolysis can be used to convert alkenes into carboxylic acids but may result in a loss of carbons.
The Bayer-Villiger reaction and SN2 reactions with carboxylate ions are alternative methods for ester synthesis.
Esterification can be achieved through Fischer esterification or by converting more reactive carboxylic acid derivatives into esters.
Phenyl Grignard reagents can be used to add an additional carbon to form a carboxylic acid through reaction with carbon dioxide.
The synthesis of an amine from an amide or nitrile can be accomplished using lithium aluminum hydride (LiAlH4).
SN2 reactions are not feasible on sp2 hybridized carbons, limiting their use in certain retrosynthetic pathways.
Amides can be synthesized from acid chlorides using nucleophilic substitution with ammonia.
Side chain oxidation, such as with chromic acid or potassium permanganate, can be used to cleave carbons and form carboxylic acids.
Friedel-Crafts alkylation is a method to introduce alkyl groups onto aromatic rings.
Multiple synthesis routes may be possible, but some are more direct and yield higher results in practice.
Strategic choice of reagents and reaction conditions can minimize the number of steps in a synthesis.
The presenter provides a study guide and practice problems for carboxylic acids and derivatives on chatsprep.com.
Final exam rapid reviews for organic chemistry topics are available, including practice final exams.
Transcripts
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