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Author: Subject: Synthesis of m-chlorocumene?
danadanadana
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[*] posted on 30-4-2012 at 07:53
Synthesis of m-chlorocumene?


Hi, I need help! We have to write a theoretical procedure for a lab to synthesize a compound from benzene or toluene. My compound is m-chlorocumene.

I have a few ideas, but it seems like I'm over-complicating it and would still run into trouble with controlling how many chlorines are added (and it would also probably be a dangerous synthesis too).

In order to get the meta position, I thought I could add a more activating group than the isopropyl or the chloride then remove it after the reaction. I was planning on using NH2, but now I see how complicated and dangerous it is to put that on and then take it off.

I found one source, some old chemistry book from the 1940s or 60s, that mentions heating to 100 degrees to acheive a meta position, and initially I thought heat would work, but I didn't find that anywhere else and that seems almost too simple? Although I'd probably still have to explain how to purify it.

Any help would be greatly appreciated! Thank you in advance!
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danadanadana
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[*] posted on 30-4-2012 at 08:04


I forgot that I should say again, this is just in theory. To some degree I think it will be impractical, otherwise our compounds would already have simple ways to make them and it wouldn't be much of a test of our knowledge!
So since it's just in theory, and we're only in organic class, not full out chemists, I think it can include a dangerous step. We just can't say to add the groups on and then just isolate out all 3% of the meta products from the largely ortho and para products.
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DDTea
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[*] posted on 30-4-2012 at 08:34


This synthesis is simpler than you think but I won't give you the answer. Instead, I'll point you to two reactions that may be helpful to you.

http://en.wikipedia.org/wiki/Electrophilic_halogenation

http://en.wikipedia.org/wiki/Friedel_Crafts#Friedel.E2.80.93...

With these two reactions in mind, which would be simpler: starting from benzene or from toluene? You want a meta substitution pattern, so which substituent should you add first: the chlorine or the isopropyl group?

When designing synthesis, try to minimize your work. Adding a group only to eliminate it is wasteful and reduces overall yields.




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danadanadana
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[*] posted on 30-4-2012 at 09:23


Thank you for your help! But I think you got me at exactly where I was stuck (and then made things more complicated for myself).

Since both isopropyl and the halogen will be ortho, para directing I can't just add them on. I see that if I start with toluene, it will direct them into the correct meta positions from each other but then I have to somehow remove the methyl group without removing the isopropyl group. I keep going back to temperature though... maybe if add the chloride to the benzene ring then perform a Friedel-Crafts dealkylation (keeping it at 0 degrees to room temp), will it go on the meta position? (then have to purify out...somehow...)

I am glad that you say it is simple though! I don't expect a full out answer either. I posted here as a last resort after thinking through a ton of different scenarios and always ending up back where I started. After all that "work", I WANT to solve this! I very much appreciate your help!

[Edited on 30-4-2012 by danadanadana]

[Edited on 30-4-2012 by danadanadana]
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DDTea
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[*] posted on 30-4-2012 at 09:48


Now I see your problem: you've got your substituents and their directing ability in electrophilic aromatic substitution reactions bass ackwards! Take some time to review this topic. :)

Chlorine is overall meta-directing and deactivates the ring. Alkyl groups (methyl, isopropyl, etc.) are ortho/para directing. EAS reactions on toluene, accordingly, will be directed ortho and para to the methyl group (2:1 ratio of o and p isomers in product).




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danadanadana
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[*] posted on 30-4-2012 at 10:18


Now I'm [more] confused... my book says that halogens, while they are weak deactivators, are ortho,para directing... (everything else you said makes sense).

maybe I'm misunderstanding what you mean...? Whatever the case, I'm sure that I'm missing something stupid though!

I appreciate the time you're taking on me! :)
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DDTea
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[*] posted on 30-4-2012 at 12:53


Well, looks like I've embarrassed myself! *face palm* You're right, chlorine is meta-directing.

So going back to your original post: you said that you considered using NH2. Were you referring to a Sandmeyer chlorination? http://www.organic-chemistry.org/namedreactions/sandmeyer-re... Because that would be a very viable route.

[Edited on 4-30-12 by DDTea]




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[*] posted on 2-5-2012 at 15:22


Danadanadana, syntheses can be and commonly have to be multistep. There are many ways to get m-chlorocumene from benzene or toluene. For example, you can make benzoic acid from toluene by oxidation with diluted HNO3 (UTFSE for references). Benzoic acid can be meta-chlorinated and the product esterified to give methyl 3-chlorobenzoate. This can be reacted with methylmagnesium chloride to give m-chlorocumyl alcohol. Then all you need to do is to reduce it to m-chlorocumene, which can be done with silanes or by careful hydrogenation in the presence of HCl (dechlorination can be an issue with hydrogenation, so for educational purposes reduction with silanes is the best choice).

Quote: Originally posted by DDTea  
Well, looks like I've embarrassed myself! *face palm* You're right, chlorine is meta-directing.

You have just embarrassed yourself for the second time!
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Lambda-Eyde
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[*] posted on 2-5-2012 at 16:16


Quote: Originally posted by Nicodem  
For example, you can make benzoic acid from toluene by oxidation with diluted HNO3 (UTFSE for references). Benzoic acid can be meta-chlorinated and the product esterified to give methyl 3-chlorobenzoate. This can be reacted with methylmagnesium chloride to give m-chlorocumyl alcohol. Then all you need to do is to reduce it to m-chlorocumene, which can be done with silanes or by careful hydrogenation in the presence of HCl (dechlorination can be an issue with hydrogenation, so for educational purposes reduction with silanes is the best choice).

That's not exactly what I had in mind, Nicodem :P But then again, hydrogenation and silanes are a bit over my head.

My suggestion would be to start with benzene, nitrate it to nitrobenzene and then run a Friedel-Crafts (do people still use that reaction?!) with isopropyl chloride/bromide. I'd then reduce the nitro to an amine and run a Sandmeyer reaction with CuCl. Four steps in total, compared to five steps in your procedure. Do you think yours would give better overall yield, or do you see any flaws in my procedure?

(Also, I thought KMnO4 was the oxidant of choice for making benzoic acid - never heard of using dilute HNO3.)

[Edited on 3-5-2012 by Lambda-Eyde]




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DDTea
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[*] posted on 2-5-2012 at 16:28


Quote: Originally posted by Lambda-Eyde  

My suggestion would be to start with benzene, nitrate it to nitrobenzene and then run a Friedel-Crafts (do people still use that reaction?!) with isopropyl chloride/bromide. I'd then reduce the nitro to an amine and run a Sandmeyer reaction with CuCl.
[Edited on 3-5-2012 by Lambda-Eyde]


This is exactly what I had in mind.

And for the record: CHLORINE IS ORTHO-PARA DIRECTING in electrophilic aromatic substitution reactions! I need to do a better job of proofreading my posts!

[Edited on 5-3-12 by DDTea]




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[*] posted on 2-5-2012 at 17:13


Quote: Originally posted by Lambda-Eyde  
My suggestion would be to start with benzene, nitrate it to nitrobenzene and then run a Friedel-Crafts (do people still use that reaction?!) with isopropyl chloride/bromide. I'd then reduce the nitro to an amine and run a Sandmeyer reaction with CuCl. Four steps in total, compared to five steps in your procedure. Do you think yours would give better overall yield, or do you see any flaws in my procedure?

Only one little flaw in the Friedel-Crafts alkylation. Like so commonly, I will cite my self here:
Quote: Originally posted by Nicodem  
As far as I know nobody ever succeeded in alkylating nitrobenzene using the AlCl3 catalysed Friedel-Crafts reaction (it is even commonly used as solvent for this reaction). Special conditions are required for ethylation (see DOI: 10.1021/jo00299a051) while methylation under these conditions does not work even on less deactivated substrates (see DOI: 10.1021/jo00025a037).

Quote: Originally posted by Nicodem  
In essence, the authors explain their hypothesis on why only Friedel-Crafts ethylations of nitrobenzene in H2SO4 are possible:
- hydride shift is symmetrical (gives the same carbocation) and irreversible decomposition or fragmentation nearly impossible;
- the substrate (nitrobenzene) does not get deactivated by protonation with H2SO4 (check pKa of PhNO2) while it gets deactivated by stronger non-protic acids such as AlCl3;
- ethanol is borderline in the formation of an extremely reactive carbocation (while methanol, being primary, can not form carbocations at such conditions).

All in all, the Friedel-Crafts ethylation of nitrobenzene in H2SO4 is a very exceptional case.

In any case, for educational reasons, knowingly giving bullshit answers is an acceptable behaviour that often helps you obtaining good grades. From this perspective, your synthetic proposal would be considered the correct answer for such an exam question. After years of experience, I tend to believe this is because teachers themselves so commonly ask bullshit questions on exams. The consequence is that they tend to accept bullshit as the correct answer even when they somehow recognize it. This is called "educational process". Totally unscientific, I know.




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