Stork Enamine Reaction Mechanism - Alkylation, Acylation, & Michael Addition
TLDRThis video script offers an insightful overview of the Stork and amine reaction, focusing on the formation of enamines from cyclohexanol and secondary amines. It delves into the alkylation of ketones using enamines, the reaction with acid chlorides to form 1,3-diketones, and the Michael addition involving alpha-beta unsaturated aldehydes or ketones. The script also explains the mechanism of enamine formation under mildly acidic conditions, detailing each reversible step and the role of weak bases in the process. The video concludes by highlighting the utility of enamines in various organic reactions, providing a comprehensive guide for those interested in organic chemistry.
Takeaways
- π§ͺ The Stork and amine reaction involves the formation of an enamine from a ketone and a secondary amine.
- π The enamine intermediate can undergo alkylation with an alkyl halide, leading to the formation of an iminium ion which can then be quenched with water to regenerate the ketone.
- βοΈ The enamine can also react with an acid chloride, forming a new iminium ion that, upon reaction with water, yields a 1,3-diketone.
- π The Michael reaction is another application of the enamine, where it acts as a nucleophile and reacts with an Ξ±,Ξ²-unsaturated aldehyde or ketone.
- π The Ξ²-carbon in Ξ±,Ξ²-unsaturated systems is electrophilic, as indicated by resonance structures showing positive formal charges.
- π― The enamine prefers to attack the Ξ²-carbon in the Michael reaction due to its electrophilicity.
- π‘οΈ The formation of the enamine requires mildly acidic conditions, with a pH around 4 to 5.
- π Protonation of the ketone is the first step in enamine formation, activating it for reaction with the secondary amine.
- π Each step in the enamine formation process is reversible, highlighting the dynamic nature of the reaction.
- π§ Water can act as a weak base in the enamine formation, aiding in the removal of a proton to facilitate the reaction.
- π οΈ The final step in enamine formation involves the use of a secondary amine to abstract a proton and form the enamine intermediate.
Q & A
What is the Stork-Zamanoski enamine reaction?
-The Stork-Zamanoski enamine reaction is a process where a ketone reacts with a secondary amine to form an enamine intermediate, which can then be used in various reactions such as alkylation, acylation, and Michael addition.
What is the structure of an enamine?
-An enamine has a single bond between the carbon and nitrogen atom and a carbon-carbon double bond, making it a conjugated system.
How does the alkylation of ketones using enamines occur?
-The alkylation involves the enamine reacting with an alkyl halide, where the nitrogen's lone pair forms a pi bond, causing the double bond to attack the alkyl group and expel a halide ion, resulting in an iminium ion that is then hydrolyzed to regenerate the ketone.
What is the role of H3O+ in the alkylation process?
-H3O+ is used to hydrolyze the iminium ion, removing the nitrogen group and regenerating the original ketone.
How can an enamine intermediate react with an acid chloride?
-The enamine reacts with an acid chloride by using the nitrogen's lone pair to form a pi bond, causing the double bond to attack the acid chloride, breaking the pi bond and forming an iminium ion attached to a carbonyl group with a chlorine atom, which then expels the chloride ion to form a ketone.
What is the final product when an enamine reacts with an acid chloride?
-The reaction results in a 1,3-diketone as the final product after hydrolysis with H3O+.
What is a Michael donor and acceptor in the context of the Michael reaction?
-In the Michael reaction, the enamine acts as a Michael donor, donating a nucleophilic pi bond, while an alpha,beta-unsaturated aldehyde or ketone acts as the Michael acceptor, which has electrophilic carbon atoms.
Why does the enamine prefer to attack the beta carbon in a Michael reaction?
-The enamine prefers to attack the beta carbon because it is less sterically hindered and more electrophilic compared to the carbonyl carbon.
What is the typical product of a Michael reaction involving an enamine?
-The typical product of a Michael reaction is a 1,5-dicarbonyl compound.
What conditions are required for the formation of an enamine?
-The formation of an enamine requires mildly acidic conditions with a pH around 4 to 5, which involves protonation of the ketone and reaction with a secondary amine.
How is the enamine formed from the protonated ketone and secondary amine?
-The secondary amine attacks the carbonyl carbon of the protonated ketone, forming an intermediate with a positively charged nitrogen atom. A weak base then removes a hydrogen to form the enamine, expelling water as a leaving group.
Outlines
π§ͺ Enamine Formation and Reaction Mechanisms
This paragraph introduces the Stork-Amine reaction, focusing on the formation of an enamine from cyclohexanol and a secondary amine. It explains the potential reactions of the enamine intermediate, including alkylation with an alkyl halide, leading to the formation of an iminium ion, and subsequent regeneration of the ketone with H3O+. The paragraph also covers the reaction of enamines with acid chlorides, resulting in a 1,3-diketone, and the Michael reaction involving an alpha-beta unsaturated aldehyde or ketone. The importance of the electrophilic nature of the carbonyl and beta carbon is highlighted, and the preference of the enamine to attack the beta carbon is discussed.
π Michael Reaction and Enamine Formation Process
The second paragraph delves deeper into the Michael reaction, describing the formation of an intermediate with a negatively charged oxygen and a nitrogen atom with a double bond. It outlines the reaction with a weak acid, typically water, to form an aldehyde functional group, and the final acidification step to yield a 1,5-dicarbonyl product. The paragraph also discusses the mechanism for enamine formation, emphasizing the need for mildly acidic conditions and detailing the protonation, attack by the secondary amine, and the steps to expel water and form the enamine, including the use of a weak base to remove a hydrogen and the role of the secondary amine in this process.
π Summary of Enamine Reactions and Mechanisms
The final paragraph provides a concise summary of the enamine intermediate's utility in various reactions, such as alkylation, isomerization, and participation in Michael reactions. It reiterates the mechanism for enamine formation, highlighting the reversible nature of the steps and the conditions required for successful enamine synthesis. The paragraph concludes the video script with a brief acknowledgment and thanks to the viewers.
Mindmap
Keywords
π‘Stork and amine reaction
π‘Enamine
π‘Alkylation
π‘Iminium ion
π‘Acid chloride
π‘Michael reaction
π‘Electrophilic carbon
π‘Resonance structure
π‘Mildly acidic conditions
π‘Protonated ketone
π‘Weak base
Highlights
Introduction to the Stork and amine reaction with cyclohexanol and a secondary amine to form an enamine intermediate.
Enamines can be alkylated with alkyl halides, using the nitrogen lone pair to form a pi bond and attack the alkyl group, expelling a bromide ion.
Formation of an iminium ion after alkylation, followed by the addition of H3O+ to regenerate the ketone.
Enamines can also react with acid chlorides, using a similar mechanism to form an iminium ion with a carbonyl and chlorine atom.
Expulsion of chloride ion and reaction with H3O+ to form a 1,3-diketone product.
Enamines can participate in Michael reactions with Ξ±,Ξ²-unsaturated aldehydes or ketones, acting as a Michael donor.
Understanding electrophilicity of Ξ²-carbon and carbonyl carbon in Ξ±,Ξ²-unsaturated systems through resonance structures.
Enamine's preference for attacking the Ξ²-carbon in Michael reactions due to its weaker basicity compared to the carbonyl carbon.
Formation of an intermediate with an aldehyde functional group and a nitrogen double bond in Michael reactions.
Reaction with a weak acid to form a 1,5-dicarbonyl product in the final step of Michael reactions.
Discussion of the mechanism for enamine formation, requiring mildly acidic conditions with a pH around 4-5.
Protonation of the ketone under acidic conditions as the first step in enamine formation.
Reaction of the activated ketone with secondary amine, leading to the formation of an iminium ion with a positive charge on nitrogen.
Use of a weak base to remove a hydrogen and transfer it to the OH group, making it a good leaving group.
Expulsion of the OH2 group by the nitrogen atom, forming a neutral nitrogen atom with a lone pair.
Final step in enamine formation using the secondary amine to remove a hydrogen and form the enamine intermediate.
Overview of the enamine's role in alkylation, isomerization, and participation in Michael reactions.
Conclusion of the video with a summary of the Stork and amine reaction mechanisms and applications.
Transcripts
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