Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: Sach on November 08, 2017, 01:56:04 PM
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I am currently working on a project of organic chemistry (like some of you already know). I got the task to make a large molecule by coupling thiophenes. Molecule 1, the protected aminothiophene,(in the attachment) is what I start with. In the attachment you can also find the proposal I have (making 2-bromo thiophene, followed my preparation of a grignard reagens and then coupling the thiophenes to each other).
Any remarks, advice or other proposals are more than welcome.
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Can't make a grignard in the presence of that carbamate. Pathway is no good.
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You could substitute the 2,5-dibromothiophene with thiophene-2,5- di-boronic acid and use the 2-bromo-3-Cbz-amino-thiophene as is using Pd(0) catalysis. I dont know if you can buy thiophene-2,5-di-boronic acid.
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Rolnor, you're better than that
http://www.sigmaaldrich.com/catalog/product/aldrich/470317?lang=en®ion=US
first thing that popped up for googling "thiophene-2,5-di-boronic acid." It can also be made without too much trouble I bet (scifinder away).
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Thank you for the quick reply guys.
Rolnor, do you mean the reaction I attached in the attachment?
Wildfyr, why is the making of a grignard not possible in presence of that carbamate?
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Grignards react with carbonyls. A carbamate has a carbonyl.
And to fill in for Rolnor, you are missing a bromine at the 1 position on your thiophene-2-carbamate to do the proposed Suzuki coupling.
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Ooh ok, thank you.
Do you have a proposal by which I can couple thiophene to thiophene-2-carbamate?
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... rolnor just proposed a method. Suzuki coupling.
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Ooh ok but I don't understand why the reaction I proposed isn't correct?
I actually didn't understood your comment 'you are missing a bromine at the 1 position on your thiophene-2-carbamate to do the proposed Suzuki coupling.'
Thank you for your understanding.
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Well what two partners do the coupling in a Suzuki coupling? Do you have those in the scheme you drew just now?
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Ooh yeah I get it. The thiophene carbamate needs a bromine.
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Yes, thats what I suggest. One problem could be steric hindrance from the Cbz-aminogroup, the reaction can be slow or you need to heat.
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Ok, I will search for a complete procedure for bromination first.
And for suzuki reaction, would I need an excess of thiophene-carbamate or would 1eq of both be sufficient?
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If you want the desired product you need 2 eq. of the thiophene-carbamate, not?
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Ooh yeah you are right.
I also have a question about bromination of thiophene carbamate. I have seen in some articles that thiophenes are brominated using NBS and using THF (of glacial acidic acid) as solvent. I don't know the mechanism by which this reaction takes place so I don't know if thiophene-carbamate can be brominated like I propose in the attachment.
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My professor did like the idea of bromination of thiophene-carbamate followed by suzuki recation as suggested by Rolnor (thanks for that Rolnor). But my professor wants me to do (or try) the reaction you can find in the attachment (using direct arylation). Now I have to find a procedure to couple thiophenes to each other using direct arylation. I can base myself on the direct arylation I have done previously but I can obviously not use exactly same conditions. I will do some research tomorrow but I have no acces to scifinder at home. Do you guys think it could work?
thank you in advance