[Sach]

I am new to this forum and I hope I am not breaking any rules of this forum by posting this question. I am currently starting a project about metal organic frameworks. In order to start the project, I first need to  find out that synthesis of which molucule (3-nitro thiophene or 3-amino thiophene) is more suited for direct arylation. Can anyone please help me out with this?


In the attachment, you can find the structure formulas of both molecules.

[wildfyr]

Tell us what you know about direct arylation. What about an aryl ring makes it suitable for this reaction? What can cause side reactions?

This is not some tiny field you are asking about, but rather a concept that is richly described in the literature. Have you read a review paper or two on it yet? This review is what I found two entries on the first page of google results for "review direct arylation" has 2700 citations, perhaps it could be of use. http://pubs.acs.org/doi/abs/10.1021/cr0509760

I've never done the reaction, but these are basic steps any chemist would take before tackling a reaction.

[Sach]

I am a masters student and I have never learnt about MOFs (or direct arylation) during my academic career. I recently started reading a book about MOFs and there was a chapter about direct arylation that I read, but to be honest I didn't understand the concept fully.
Thank you for your advice, I will start reviewing direct arylation on the internet.

[kriggy]

Maybe show the product of arylation you want to achieve -  at least in general. Do you want to arylate the thiopnene or carbon or on the amino group?

[Sach]

I want to arylate carbon (actually both carbons C2 and C5).
The following product should be the one I need to synthesize.

[rolnor]

I think you could do Suzuki reaction with 2,5-diiodo-3-acetamidothiophene and 4-ethoxycarbonylphenylboronic acid, then hydrolyze the acetamid and ethylester-groups in one step. I think synthesis of the startingmaterial can be find with Scifinder etc. Or maby the other way with the boronic acid-groups on the thiophene-ring and iodo on the phenyl-ring. I would try palladium as catalyst first.

[wildfyr]

I like rolnor's approach, except that 2,5-diiodo-3-acetamidothiophene is not commercially available, and probably is a pain to make. 2,5-dibromo-3-nitro thiophene, however, is buyable, if expensive: http://carbosynth.com/carbosynth/website.nsf/(w-productdisplay)/4DE311093ED17E2E482580C5000D3FFC.  Nitrating 2,5-dibromothiophene probably isn't hard and may be much cheaper if you want more than a few hundred mg.

You can reduce the nitro quite easily after the coupling reaction (or even probably do the hydrolysis and reduction in one step using something like a Bechamp reduction).

The boronic acid derivative he mentioned is fairly cheap and available however.

[Sach]

Thank you for the reply guys. I really appreciate it.

[Sach]

I have got one more question. Which of the following molecules would be easier to prepare in the lab? I thought 3 aminothiophene is easier to prepare but I am not sure. Thank you in advance.

[wildfyr]

Do you have access to Scifinder? It will allow you to do some of the legwork yourself, and learn a lot more about organic chemistry in the process than you would get by us giving away the answer.

[Sach]

My professor was going to give me access to scifinder but I haven't gotten it yet.

[wildfyr]

Maybe ask again if its been a few days. Its a really worthwhile use of your time to learn how to use it, and go through the process of using it to examine reaction conditions.  Many schools also have something called Reaxys which is similar.

"Easier to prepare" may also depend on what reagents and equipment you have already in lab.

[kriggy]

Yeah, check the review posted by wilfyr.
I did because it looks like an interesting synthesis. You probably want to see scheme 275 at page 230. ALthough my initial approach would be different:

[Sach]

Thanks a lot guys! I have now gotten access to scifinder but only when I am on the campus, I can't use it at home. I guess I will be on the campus more often now to get used to scifinder. My professor also told me that one can learn a lot through scifinder.

[rolnor]

Kriggy,
Is it not risc that you get attack on the ketone-carbonyl in the first step rather than substitution of the bromide?
Also the amino-ketone looks difficult, you have a aminogroup as free base together with twoo ketone-carbonyls.