jmister28
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Would it be possible to make 2-bromobenzoyl chloride from salicylic acid
Due to the similarities of 2-bromobenzoyl chloride and salicylic acid, would it be possible to synthesize it? If so, what reagents and reactions would
be necessary to synthesize such a molecule. Any contribution helps
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Nakhimov
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It would definitely be viable! If I were doing the synthesis in my own lab
1. Protection of carboxylic acid
2. Bromination of alcohol group (Appel rxn, HBr, or similar)
3. Deprotection of COOH
4. Chlorination of carboxylic acid
5. Workup
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jmister28
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what would you use for the protection of the carboxylic acid and the deprotection of COOH?
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Loptr
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Nope, not like that.
Phenol cannot undergo an SN1, E1 or SN2 reaction. For SN1 and E1, it's because an unfavorable phenyl cation would have to be formed. As for SN2, which
is done by a backside attack, and given the planar nature of phenol, the nucleophile cannot attack.
An E2 reaction would be possible to produce the very reactive benzyne intermediate, but you are not guaranteed where it will end up or that it will
react like you want it to. My guess is that you would get biphenyl.
[Edited on 19-12-2018 by Loptr]
"Question everything generally thought to be obvious." - Dieter Rams
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Nakhimov
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Depends on what you have available to remove the PG. Probably a benzyl ester.
edit: oops, good point! You're right that the aryl alcohol would be a bit stubborn. You could go through the Sandmeyer reaction. That would actually
make things easier, I think.
[Edited on 12-19-2018 by Nakhimov]
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Loptr
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Quote: Originally posted by Nakhimov  | Depends on what you have available to remove the PG. Probably a benzyl ester.
edit: oops, good point! You're right that the aryl alcohol would be a bit stubborn. You could go through the Sandmeyer reaction. That would actually
make things easier, I think.
[Edited on 12-19-2018 by Nakhimov] |
But then you are talking about starting from an anthranilic acid, and not salicylic acid.
"Question everything generally thought to be obvious." - Dieter Rams
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Nakhimov
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| Quote: Originally posted by Loptr | | Quote: Originally posted by Nakhimov | Depends on what you have available to remove the PG. Probably a benzyl ester.
edit: oops, good point! You're right that the aryl alcohol would be a bit stubborn. You could go through the Sandmeyer reaction. That would actually
make things easier, I think.
[Edited on 12-19-2018 by Nakhimov] |
But then you are talking about starting from an anthranilic acid, and not salicylic acid. |
Good point. Think it would be easier to start from benzene, brominate, then acylate followed by SOCl2?
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clearly_not_atara
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The answer is probably not unless you can use Tf2O or chlorodiphenylimidazolium.
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CuReUS
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you can simultaneoulsy convert the OH and COOH of salicylic acid to bromobenzoyl bromide using appel reaction alone.
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AvBaeyer
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Does anyone bother to do a simple google search before making somewhat useless comments?
The critical part of the OP's problem: is it possible to convert a phenolic OH to an aryl halide? Search: "phenol to aryl halide." You will find some
answers which are informative but perhaps not imminently practical. Will these reactions work with salicylic acid/esters? Follow it up as there are
hints that they might.
By the way, the Appel reaction will not work at all. Look it up.
Google and Google Scholar are extremely powerful for leading to possible answers for questions of the type being asked. I do not understand why these
resources are not used more so that good questions can be asked and more informative answers provided.
AvB
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CuReUS
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https://www.sciencedirect.com/science/article/pii/0040402093...
https://www.thevespiary.org/rhodium/Rhodium/Vespiary/talk/fi...
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Chemi Pharma
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Reading the papers @Cureus brought, I remembered about another paper telling how to convert carboxilic acids into acid chlorides and alcohols to
chlorides using TCCA and triphenylphosphine in anhydrous acetonitrile. It seems the mechanism of the reactions are similiar: triphenylphosphine forms
triphenylphosphine halide and this intermediate promotes the substitution of the (OH) group in acids and alcohols by chlorine.
Although the paper (attached below) didn't exemplificates this kind of reactions with phenols, based in @Cureus papers, I guess both phenolic and
carboxilic groups at first and second positions of the benzene ring in salicylic acid will be replaced at once, giving the product OP's desire:
2-chloro benzoyl chloride.
If it doesn't work, I sugest the conversion of salicylic acid into anthranilic acid with chloroacetamide, K2CO3, KI and DMF, like the paper I attached
below say --> Sandmayer reaction on anthranilic acid to substitute the amino group by an halide group --> Formation of the acid chloride with
TCCA and triphenylphosphine in anhydrous acetonitrile like I've said above, following the guidelines inside the paper I've attached too.
Attachment: acid chlorides with TCCA and triphenylphosphine.PDF (172kB)
This file has been downloaded 362 times
Attachment: phenols to anilines with chloroacetamide, K2CO3, KI and DMF.PDF (1.9MB)
This file has been downloaded 399 times
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Loptr
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@chemi pharma,
Why do you think that reagent pair will form the acyl halide? I only see an example of forming an ester in that paper, which would have been through
formation of the alkyl chloride, and then reaction with the carboxylic acid, and not the other way around.
Also, remember the formation of an acyl halide is through the double bonded oxygen, and not just a simple substitution of the hydroxyl. Also, the
carboxyl group is a resonance structure, and acts as a single unit, and does not behave the same as its individual parts.
[Edited on 26-12-2018 by Loptr]
[Edited on 26-12-2018 by Loptr]
"Question everything generally thought to be obvious." - Dieter Rams
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Chemi Pharma
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| Quote: Originally posted by Loptr | @chemical pharma,
Why do you think that reagent pair will form the acyl halide? I only see an example of forming an ester in that paper, which would have been through
formation of the alkyl chloride, and then reaction with the carboxylic acid, and not the other way around.
Also, remember the formation of an acyl halide is through the double bonded oxygen, and not just a simple substitution of the hydroxyl. Also, the
carboxyl group is a resonance structure, and acts as a single unit, and does not behave the same as its individual parts.
[Edited on 26-12-2018 by Loptr] |
I do not desagree with you. The paper I brought I have catched with @AVBayer and really don't explain the things too much clear. But I have another
paper explaining better the mechanisms envolved with the same couple reactions (TCCA and triphenylphosphine) used to achieve acyl chlorides from
carboxilic acids and also amides and esters. I'm attaching it right now.
You can use cyanuric chloride and TEA too, to convert carboxilic acids into acid chlorides. I'm attaching another paper related below.
Of course you are right and I know its not a simple (OH) substitution. I wrote this way only to simplify the things. I didn't want to explain the
mechanisms of the reaction. I think is boring and takes a long time. Let the papers explain it for me in a better way.
Enjoy the papers.
Attachment: acids to amides with TCCA and triphenylphosphine.PDF (105kB)
This file has been downloaded 333 times
Attachment: Acid chlorides from acids with Cyanuric Chloride and TEA.pdf (86kB)
This file has been downloaded 322 times
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AvBaeyer
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I do not want to reopen an old discussion, but attached is the text part of an Organic Reactions chapter on "oxyphosphonium" chemistry, which
mechanistically includes the Appel reaction. Hopefully, folks here will find this interesting and useful.
AvB
Attachment: Oxyphosphonium chemistry OrgRxns castro1983.pdf (1.8MB)
This file has been downloaded 384 times
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