Alkynide Alkylation - Online Tutor, Practice Problems & Exam Prep

Understanding the formation of carbon-carbon bonds is crucial in organic synthesis, primarily through organometallic compounds and sodium alkynides. These strong nucleophiles react with alkyl halides, facilitating the creation of new bonds. Key processes include generating alkynides, utilizing them in reactions, and transforming triple bonds into double bonds. Mastery of these concepts is essential for progressing in synthetic chemistry, as they form the foundation for constructing larger molecules from smaller ones, highlighting the importance of nucleophilicity and electrophilicity in organic reactions.

Sodium Alkynide Alkylation

Part of the synthetic cheat sheet taught you guys how to make new carbon-carbon bonds, and that's what I want to focus on in this topic. I really just want to deconstruct the entire concept of organometals and sodium alkynide alkylation. So basically, you guys know this is the only way to make carbon-carbon bonds in Orgo 1, through organometals, and strong sodium alkynides are really commonly used organometals because they happen to be strong nucleophiles. What that means is that since they are strong nucleophiles, they are often paired or reacted with alkyl halides because those are strong electrophiles. What we can do is we can get a negative on a carbon to be attracted to a positive on a carbon and bam, you have a new carbon-carbon bond, which is very important because synthesis relies on making bigger molecules from smaller ones. So, if you can add carbons, that's really important, okay?

But for these sodium alkynides, we're not just going to need to know that it's a nucleophile engaging in six electron. We're going to need to know a few more things. How to generate the alkynides. So that means alkynide synthesis, making it from scratch. We need to know how to do that. Also, after you've done your reaction, you also need to know how to transform the triple bond afterwards. So there's a lot to know here. We need to know how to make the alkynide, then how to use it, and then how to lose it. How to do different things to it. Okay?

So once again, I had this graphic that showed different nucleophiles. The ones we're going to be dealing with mostly on this page because I want you guys to get special practice with these are the alkynides and the alkyl halides. So what we're going to do first is we're going to start from, in kind of ascending order of difficulty, we're going to start with the easiest problem. It's not easy, but it's not that bad. And we're going to work our way to progressively harder and harder problems where I'm going to take you further and further back in the synthetic process and you're going to have to figure out everything from the very beginning. But in this case, like I'm telling you right now, this is not such a bad question. Let me coach you through it and see if you can get it. Because notice that right now, first of all, I'm already starting with a triple bond. That's awesome. Because if you're going to notice, I have 3 carbons in this molecule. I have 4 carbons in the other. Okay?

What does that mean that must have happened at some point? Okay? If I added carbon, if you added carbon, that means you must have used an organometal. And like I said, the most common organometal in this chapter is going to be sodium alkynide. And I already have a triple bond, so it's a huge giveaway that I just need to use that triple bond. So basically, what you should be thinking is how many carbons do I need to add to the triple bond for it to make 4 and then what do I need to do to that triple bond after so it looks like a double bond. It looks like that. So those were enough hints. I'm just trying to coach you guys. So this isn't totally like a train wreck. And I'm gonna stop the video and you guys try to answer it the best that you can.

Propose a synthesis:

• A. 1) H₂/Lindlar's Catalyst
  2) KMnO₄, OH^-, Δ / H⁺
  3) NaBH₄
  4) CH₃MgBr
• B. 1) LiAlH
  2) CH₃Cl
  3) H₂/Pt
• C. 1) NaNH₂
  2) CH₃Br
  3) H₂/Lindlar's catalyst
• D. 1) O₃, Me₂S
  2) EtLi / H₃O⁺
  3) LDA

Propose a synthesis:

• A. 1) Cl₂
  2) CH₃ONa (excess)
  3) CH₃Br
  4) H₂/Pt
• B. 1) O₃, Me₂S
  2) EtLi / H₃O⁺
  3) LDA
• C. 1) Br₂
  2) NaNH₂ (2 eq.)
  3) H₃O⁺/H₂O
  4) CH₃MgBr / H₃O⁺
• D. 1) Br₂
  2) NaNH₂ (excess)
  3) CH₃I
  4) Na/Liq. NH₃

• A. 1) Br₂ / Δ
  2) LDA
  3) Br₂
  4) NaNH₂ (2 eq.)
  5) H₃O⁺/H₂O
  6) EtMgBr / H₃O⁺
• B. 1) Br₂ / Δ
  2) LiTMP
  3) Br₂
  4) NaNH₂ (2 eq.)
  5) O₃, Me₂S
  6) CH₃CH₂CH₂MgBr
• C. 1) Br₂ / Δ
  2) KOC(CH₃)₃
  3) Br₂
  4) NaNH₂ (excess)
  5) CH₃CH₂I
  6) H₂/Pt
• D. 1) Cl₂ / Δ
  2) NaH
  3) Br₂
  4) NaNH₂ (2 eq.)
  5) KMnO₄, OH^-, Δ / H⁺
  6) CH₃CH₂CH₂MgBr

Here’s what students ask on this topic:

What is the role of sodium alkynides in organic synthesis?

Sodium alkynides play a crucial role in organic synthesis by acting as strong nucleophiles. They are used to form new carbon-carbon bonds, which is essential for building larger molecules from smaller ones. Sodium alkynides react with alkyl halides, which are strong electrophiles, to create these bonds. This process is fundamental in synthetic chemistry, as it allows for the construction of complex molecules, facilitating various transformations and functionalizations of the resulting compounds.

How do you generate sodium alkynides?

To generate sodium alkynides, you typically start with a terminal alkyne. The terminal alkyne is treated with a strong base, such as sodium amide (NaNH₂), which deprotonates the terminal hydrogen, forming the sodium alkynide. The reaction can be represented as:

${R-C\equiv C}_{-}+{\mathrm{Na}-\mathrm{NH}}_2\to {R-C\equiv C}_{-}$

What are the common reactions involving sodium alkynides?

Common reactions involving sodium alkynides include nucleophilic substitution reactions with alkyl halides to form new carbon-carbon bonds. This reaction is crucial for extending carbon chains in organic synthesis. Additionally, sodium alkynides can participate in various transformations, such as hydrogenation to form alkenes or alkanes, and coupling reactions to create more complex structures. These reactions are fundamental in constructing larger and more intricate organic molecules.

How do you transform a triple bond into a double bond after alkynide alkylation?

After alkynide alkylation, a triple bond can be transformed into a double bond through partial hydrogenation. This process involves using a catalyst, such as Lindlar's catalyst, which selectively hydrogenates the triple bond to a cis-alkene. The reaction can be represented as:

${R-C\equiv C}_{-}+H_2\to {R-C=C}_{-}$

This selective hydrogenation is crucial for maintaining the desired stereochemistry in the resulting alkene.

Why are alkyl halides used in reactions with sodium alkynides?

Alkyl halides are used in reactions with sodium alkynides because they are strong electrophiles. The halogen atom in alkyl halides is highly electronegative, making the carbon atom it is attached to electron-deficient and thus susceptible to nucleophilic attack. Sodium alkynides, being strong nucleophiles, readily react with these electrophilic carbon atoms in alkyl halides, facilitating the formation of new carbon-carbon bonds. This nucleophilic substitution reaction is a key step in extending carbon chains and constructing more complex organic molecules.