Now let's discuss how Friedal-Crafts Acylation is so much more effective than Friedal-Crafts Alkylation. So Friedal-Crafts Acylcation has several advantages that are going to make it much more synthetically useful than alkylation and a few of these we've already discussed basically that acylation reactions are going to deactivate the ring to further reactions favouring mono substitution which is a big deal in organic chemistry synthesis. We want to make sure that we're only adding one group at a time not two, not four. Also we learned that acylation reactions are not susceptible to carbocation rearrangement because the acylium ion can't resonate. Perfect, so here I just want to show you as an example for how two synthesis could go completely different directions depending on which one you use. So let's say that we're trying to add a three carbon chain to the benzene ring. First we're going to use acylation. Acylation, what I'm going to wind up getting is an acylium ion that looks like this. It's going to be carbon with double bond O positive and a three carbon chain. Everyone cool with that? So I'm going to wind up attacking and after all our arenium ions don't worry about it too much we're going to wind up getting a product that looks like this. It's going to have a three carbon chain, it's going to be a ketone with a three carbon chain and that's it we're not going to get a second reaction we're not going to get a rearrangement that's it. Now notice what happens when we try to use alkylation. Alkyaltion may seem like the more, the better choice because we don't want the ketone we just want the chain.
So our first thought would be let's just use alkylation because alkylation doesn't give us that ketone but guys alkylation is going to give so many more problems because look at this. What happens when the bond gives its electrons to the aluminum? Remember guys that primary carbocations are unstable right so that means that a rearrangement is actually going to happen right in the mechanism right away this H is going to wind up doing a 1, 2 hydrite shift and making a carbocation that looks like this so all of a sudden my carbocation doesn't look like a three carbon chain that's a street chain it looks like a branch chain it's attaching in the middle. So what I'm going to wind up getting is I'm going to wind up getting now an isopropyl benzene but that's not all I'm going to get, I might actually get another isopropyl or I might even get another one, who knows? I'm going to get a poly-substituted, poly-isopropyl benzene. All I wanted was a three carbon chain and look what a disaster this is. This is why alkylation is so limited and why we're usually going to go with an acylation over an alkylation because alkylation just gives us a mess of rearranged products and possible poly-substituted products. Now there is one way to overcome this which would be for this specific reaction what we could do is we could increase the equivalence of benzene. Now I noticed here I put one equivalent each of both of these. If I really want to use alkylation I could increase the equivalence.
Let's say I made it to one hundred equivalence of benzene. Now that would promote mono-substitution. That would promote mono-substitution because now I have excess benzene that most likely isn't going to find that many carbocations to react with, most likely it only reacts with one but still that would still give me an isopropyl benzene so even in that case I would still have isopropyl benzene because it's going to rearrange. So it's like acylation give us exactly what we want but unfortunately there's that stupid ketone. If only there was a way to get rid of that ketone then we would have a three carbon chain exactly the way we want it. Wait, we do have a way to get rid of that ketone and that is the glorious advantage of Clemmenson reduction. So it turns out that acylation products can be converted to alkylbenzenes using a reagent called the zinc amalgam in a reaction called the Clemmenson reduction. Now the mechanism for this reaction is still unknown to this day. No one really knows what the mechanism is but you do need to recognise and memorise the reagents. The reagents are a zinc, mercury amalgam over a strong acid H C L and what that's going to give us is it's actually going to add hydrogens to where the carbonyl was was and it's just going to give us an alkyl product meaning that guys if we want to get a three carbon chain instead of using an alkylation I could just use an acylation and then do a Clemmenson reduction and get rid of that carbonyl and we're done so let me show you guys the true, the best way to prepare n-propylbenzene. Now if you guys don't remember if you see that little N in the front that just means it's a straight chain so we're trying to get N straight chain three carbon benzene. What we could do is we could acylate first that's going to give me a mono-substituted product that looks like this it's a ketone that's not what we want but wait we've got Clemmenson reduction. What does Clemmensen reduction do? It zaps that carbonyl completely so I'm going to take myself out of the screen what I wind up getting is just n-propyl benzene which is what I wanted. So this is why we're going to really emphasize that acylation is better than alkylation and any time you want to add an R group try adding it with an acylation first and then doing a Clemmenson because it's probably going to be more efficient. So that's it for this video, let's move on to the next.
Provide reagent to complete the following chemical transformation.
Provide reagent to complete the following chemical transformation.
Propose three separate syntheses of isopropyl benzene starting from benzene and any other necessary reagents.
Provide the reagents to accomplish the transformation below. More than one step might be required for the transformation.
Which sequence of reagents would effect this conversion in highest yield?
Which sequence of reagents would produce propylbenzene from benzene?
Friedel-Crafts acylation has a few advantages over Friedel-Crafts alkylation and uses a Lewis acid catalyst and an acyl chloride to add an acyl group to benzene. The ketones produced can be reduced to alkyl groups using Clemmensen reduction.
Acylation vs alkylation
Say you want to get to n-propylbenzene. How would you do it? Could you use Friedel-Crafts alkylation? Nope! The carbocation that would result would rearrange from a primary carbocation to a secondary like in the mechanism below:
Friedel-Crafts alkylation mechanism
Notice that the substituent added is actually an isopropyl instead of a straight-chain propyl group because of the hydride shift. Additionally, the added alkyl group would actually activate the benzene to react further and add more isopropyl groups. Let’s actually look at this chart to see the relative disadvantages of Friedel-Crafts alkylation:
No reaction with deactivated benzene
*Another limitation is that acylation doesn't work with vinyl or aryl halides.
Okay, so we know that our direct and obvious limitation in this case is the carbocation rearrangement. Friedel-Crafts acylation is not subject to carbocation rearrangement, so let’s try that instead:
Friedel-Crafts acylation mechanism
Let’s break this down step by step. The chloride first dissociates to form a bond with the AlCl3 to form the acylium ion (the carbocation on the carbonyl carbon) which does not rearrange. The benzene then attacks the cation, and the chlorine removes a hydrogen to restore aromaticity.
That ketone makes that substituent an electron-withdrawing group, making the benzene deactivated, so the benzene will only be monoacylated. From there, all that’s left is to remove that carbonyl by using Clemmensen reduction (zinc amalgam in HCl) or Wolff-Kishner reduction.
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