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Substitution Reactions

By James Ashenhurst

Common Blind Spot: Intramolecular Reactions

Last updated: January 24th, 2020 |

So I bought a belt today (pleather, 75 cents at the Goodwill).  and decided to show it off. This is me putting it together.

belt analogy for intramolecular nucleophilic substitution reactions

This is what it looks like now:

image of two belts together

At this point you’re probably saying WTF: that’s not what a belt is supposed to look like when you put it together. That’s because I linked it together with my other belt.

I say: broaden your horizons of how nucleophiles and electrophiles can meet.

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Here’s a typical reaction you meet early on in Org 2. Formation of an ether through the addition of an oxygen nucleophile to an alkyl halide. This is the Williamson ether synthesis.

formation of ethers from alcohol and alkyl halide in presence of base is williamson ether reaction

Makes some sense, right? Nucleophile, electrophile: give the product.

Here’s the same reaction. Exactly the same. But a lot of students I talk to will look twice at it the first time they see it,  not quite sure what to do.

sodium hydroxide as base with alcohol alkyl halide leading to cyclic ether

Different example: the Friedel Crafts acylation between aromatic rings and acyl halides.

example of friedel crafts acylation reaction benzene alcl3 intermolecluar

Then, here’s the exact same reaction. Common result: hesitation. What happens?

apply same concepts of intermolecular reaction to intramolecular friedel crafts

Last example: formation of esters from alcohols and carboxylic acids. The Fischer esterification. Once people see this, they usually find it straightforward.

fischer esterification reaction intermolecular

But then hand them this reaction, and it’s a stumper.

fischer projection intramolecular

What do all of these reactions have in common?

When the nucleophile and electrophile are on the same molecule, they form RINGS.

examples of intramolecular reactions sn2 friedel crafts and lactonization

Because you’re probably used to seeing linear molecules – not chains – it looks weird.  But if you think about it, you’re already familiar with an example of this:

closing a belt is an intramolecular reaction

Comments

Comment section

6 thoughts on “Common Blind Spot: Intramolecular Reactions

  1. very interesting to get this web,i am a science teacher at blind school,some times it is very difficult to me to teach my students .big up!!

  2. I despise intramolecular reactions with a white hot passion, particularly when it comes to retrosynthetic analysis. Give me a bunch of rings all stuck together, and I crumple into the fetal position crying for my Mommy. No idea how to tackle them. Generally no idea on what the linking sites on precursors are, or how to systematically approach problems.

    IMHO, it is barely taught at all in organic classes. Most books seem to barely mention intramolecular reactions, let alone scrutinize it as a troublesome area for students. And when it is taught, it isn’t taught very well. Frequently it just seems to pop upon tests for the purposes of destroying students.

    The lack of emphasis on this topic seems utterly bizarre to me considering how incredibly important it is in chemical synthesis and in biochemistry.

  3. Can you please tell me if there will be ring formation in case of a molecule where the nucleophile and electrophile are at the ends of a very long aklyl chain?

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