Sleaspold
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hofmann rearrangement on Ibuprofen?
I know very little about ring stability and group reactivity when it comes to organic chemistry (I make mostly inorganics) but I want to get a little
bit into it... So far the only chemicals I have access to are household materials and medication. I see Ibuprofen as a very interesting compound whose
chemistry is quite intriguing...
This is what I am planning to do
What I really want to do is to latter oxidise that amino group into an hydroxide group... I was thinking on doing that in a Sandmeyer style...
What do you think guys? Thanks in advance
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Crowfjord
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Mood: Ever so slowly crystallizing...
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Sounds like a good project. Have you seen this related thread?
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Sleaspold
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That post is filled with creativity, love it!! What I am actually trying to do is the 4-chlorobenzoate of the resulting alcohol and test the resulting
molecule in organic systems... mostly bacterial cultures and see what happens, maybe nothing or maybe something very interesting who knows 
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Sleaspold
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So I came up with the following maths for the first part of the synthesis following the procedure on this post: http://www.sciencemadness.org/talk/viewthread.php?tid=4201&a...
Mix 12g of Ibuprofen with 10.5g of Urea and 0.54g of Boric acid on a round-bottom flask and reflux the mix for 2.5 hours at 180°C on a sand bath.
After refluxing add 40mL of water while hot, boil the mix and add 3mL of 28% Ammonia solution.
After that, evaporate the water and to the solid mix add 26mL of ethanol and filter. Wait for the ethanol to evaporate and recrystalize the product
over ethanol... If there is still solids on the filter paper I would try to dissolve that in ethanol and see if there is still Ibuprofenamide on
there.
I'm going to try this over the week.
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CuReUS
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You can get that in two steps:-
1.Convert ibuprofen to its lithium salt and react with p-chlorophenyllithium to get the ketone -http://pubs.acs.org/doi/abs/10.1021/jo00900a020
2.Do a baeyer-villiger reaction on the ketone to get the desired ester.
You can get lithium from batteries.The aryl lithium can be made by reaction p-chlorobromobenzene with Li
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Sleaspold
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Interesting reaction I haven't heard of it before... I am not sure if working with organolithium reagents in my house is a good a idea, aren´t they
pyrophoric and very prone to fire? I have cero experience with inert atmosphere also.
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CuReUS
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In that case,you could convert the COOH of ibuprofen to CN using the one pot urea/sulphamic acid method.Then react it with p-chlorophenylMgBr to get
the ketone and finally do the BV to get the desired ester.
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Sleaspold
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I can do that ... Where can I get more information about the one pot urea / sulphamic acid method? Is there a paper you can point me to? I would be
very thankful!
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Sleaspold
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I found this paper talking about the method but would not the temperatures involved be a problem? Since the boiling point of Ibuprofen is 157 ° C and
the procedure calls for 190 ° C would have to be refluxing the mixture ... With water at 80-90 ° C on my condenser it could be done without the risk
of pluging the condenser right
https://worldwide.espacenet.com/publicationDetails/originalD...
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CuReUS
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http://www.sciencemadness.org/talk/viewthread.php?tid=38017 - another reference for the urea/sulphamic acid route
But apparantly it is low yielding and all the references using it talk about benzonitriles rather the alkyl nitriles.That's why I found 2 other
methods to convert the acid to CN directly:-
1.http://www.sciencedirect.com/science/article/pii/S0040403907...
2.http://www.sciencedirect.com/science/article/pii/S0040403907...
the 2nd method requires too many reagents so I think the 1st one is better
Can you run microwave reactions ? because there are few procedures for converting COOH to CN in MW
I was searching for a reference for the grignard step but couldn't find any.But if you use p-chloroidobenzene,you might be able to make the ketone
without going through the grignard reagent at all - http://pubs.acs.org/doi/abs/10.1021/ol300153f
[Edited on 14-3-2017 by CuReUS]
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