[Sach]

Hi guys, I need to synthesize 3-aminothiophene since it is not commercially available at a good price and my professor doesn't want me to work with N-boc-3-aminothiophene.
The only method I have found on scifinder is the decarboxylation of 3-aminothiophene-2-carboxylate but a lot of steps are involved if I use decarboxylation for the preparation of 3-aminothiophene. Does anyone know a better (and easier) way to prepare 3-aminothiophene?
Thnx in advance

[Sach]

I am going to use decarboxylation of 3-aminothiophene-2-carboxylate. I just need to find the exact reactants and conditions being used.

[pgk]

An Easy Synthesis of 3-Amino- and 3-Nitrothiophene, Synthetic Communications, (1995), 25(23), 3729-3734
http://www.tandfonline.com/doi/abs/10.1080/00397919508011446

[wildfyr]

I love the article name.

[Sach]

Yes, that's the article I used. Thanks anyways

[Sach]

I tried the method mentioned in the article above. I started with 5g of methyl-3-amino-2-thiophenecarboxylate and decarboxylated it like mentioned in the article. After the last step (evapôration of the solvent), I just got 0,2g of the product left and after the tlc analysis, I could see that the end product (which is supposed to be 3-aminothiophene) still contains methyl-3-amino-2-thiophenecarboxylate (starting material). Does anyone know a better method for decarboxylation of methyl-3-amino-2-thiophenecarboxylate to get 3-aminothiophene?

[sjb]

How long did you leave before working it up compared to the paper? What was your (mini)-work-up like for TLC sampling during the reaction?

[pgk]

In the US patent 2278762-(1942), is clearly stated that: “free amines of heterocyclic sulfur compounds are highly unstable toward oxidation and polymerization in themselves, as to make their manufacture and any industrial use impractical”.
Thus, it’s not a bad idea to repeat the procedure under slight nitrogen flow and adding 1-2% of an antioxidant, such as BHT or BHA.

[wildfyr]

Good find pgk! OP, this also means the bench stability of this compound could be low. The decarboxylation also takes places at high temperature, which could mean that this procedure is poorly suited for what you are doing.

Perhaps the HCl salt is stable? For either during the reaction or storage of the product. Its very common to see that.

[rolnor]

I think you have to be careful when evaporating, the product is volatile.

[rolnor]

You can buy thiophene-3-carboxylic acid and do a Curtius-rearangement to the thiophene-3-isocyanate, then boil this in toluene with benzylalcohol, then you will get the Cbz-protected 3-aminothiophene without having to handle the sensitive free aminothiophene.

[wildfyr]

If you do a Curtius rearrangement be careful! It can be exothermic to the point of explosiveness.

Why won't your prof let you use N-Boc-3-aminothiophene? Its a little pricey at $45 a gram, but once you fail a few times doing other ways you've blown right past that price point.

[rolnor]

If you have a solution in toluene its safe to do Curtius. I have suggested N-Boc-3-aminothiophene but Sachs professor dont want him to work with that.

[Sach]

I am going to use 3-aminothiophene for direct arylation and my professor said that Boc protected aminothiophene won't be stable in the conditions we are going to use. Thank you everyone for the reply. Currently I am also watching videos and reading a book about laboratory techniques for organic chemistry because I am a student of applied engineering and I don't have a lot of lab experience for organic synthesis. on monday I will try the same procedure (for decarboxylation) under supervision of my professor to see whether or not I made a mistake during the lab session.

[wildfyr]

Ah well you can at least buy the Boc-protected thiophene and use it to (very) easily make the aminothiophene instead of doing all this other difficult running around. I'm rather surprise that there will be conditions that can handle a free amine but not a Boc group