[Dexter]

Hi all,

I wonder if thiophene is easily brominated at the 3rd or 4th position if I were to use bromine.

Thank you in advance.

Dexter

[sjb]

Can you clarify what you mean by the 3rd and 4th positions? Is the numbering system you're using the same as in this picture?



S

[Dexter]

Can you clarify what you mean by the 3rd and 4th positions? Is the numbering system you're using the same as in this picture?



S

That's right.

[sjb]

As far as I can remember, it's usually halogenated at the alpha (2/5) positions, unless you're using extreme conditions.

Don't have my reference books handy to find a reference, but it should be in something like Joule and Mills or similar

S

[IFP]

You can't obtain 3,4-dibromothiophene by direct bromination (Br2, NBS or whatsoever..).
Thiophene is brominated by Br2 in a sequence:
thiophene --> 2-bromoTh --> 2,5-dibromoTh --> 2,3,5-tribromoTh, 2,3,4,5-tetrabromoTh.
tetrabromothiophene can be obtained in one step from thiophene in mild conditions.

3,4-dibromothiophene can be obtained by reduction/debromination of 2,3,4,5-tetrabromothiophene with powder Zn.
This is a common route to 3,4-dibromothiophene (in 2 steps), both steps are straithforward and can be done in common chemistry lab in a large scale. We did it in 400 g scale (max flask size needed ,3 l).
See as example: K.Araki, H. Endo, G. Masuda, T. Ogawa, Chem Eur J, 2004, vol.10, 3331-3340

[IFP]

.. and, BTW, the total yield in two steps is >70-75%

[Dexter]

Thanks for the info. Does NBS brominate the 3rd or 4th position of a deactivated thiophene? Actually, I am trying to brominate 2,2'-thenil at the 5th positions of both thiophene units. Bromine in acetic acid seems to brominate at the 4th position as well... and separation is like impossible... No literature has reported this before...

[kiwi]

How about lithiation (should be selective for the 5-position?) then a low temperature quench with a halogen source at low temp (Br2 or I2)

[orgopete]

Given that a simple chromatography is difficult, I might try a low tech method. First, since the bromination prefers to occur at C-2, I would under-brominate the thienylthiophene. I will guess that separating unbrominated from monobrominated would be easier. I would again mono-brominate in a manner to give recovered starting material. Now, I might just try recrystallization. I am betting the symmetrical dibromide will be the least soluble.

Also, I would look at some literature about preparation of 2-bromothiophene. I see there are some additional and supposedly selective reagents for doing this.

I agree with the metallation possibility. I don't have ready access to the literature, but I would research this before I tried it. There are a number of preparations of 3-bromothiophenes from 2-bromothiophene by treatment with sodamide. As I recall, this may be a metallation reaction and some additional chemistry. So, I would look this stuff up.

In searching, this was an intriguing method, a photochemical coupling of thiophenes. A Google book result showed that a photochemical coupling of thienes in the book "Thiophenes", p 809. This is how it would work for this problem. Take 2,5-dibromo and 2-bromothiophene and photochemically couple them. If this trimerizes as well, then slowly add 2-bromothiophene and stop at max pdt. This would be the method I would try. I think the starting materials are commercially available though I did not look that up.

[kiwi]

There are a number of preparations of 3-bromothiophenes from 2-bromothiophene by treatment with sodamide. As I recall, this may be a metallation reaction and some additional chemistry.

That's one of these:

http://en.wikipedia.org/wiki/Halogen_dance_rearrangement

[Dexter]

Thenil is the diketone of thiophene. I'm referring to 2,2'-thenil to be precise.

http://www.chemicalbook.com/CAS%5CGIF%5C7333-07-5.gif

Bromination of this is rather tricky as bromine at room temperature does not work due to the strong electron withdrawing group. Refluxing in chloroform form the 5,5'-dibromo product but reaction doesn't seem to go into completion even at 3 equivalence of bromine. Monobrominated compound is observed, with the presence tribrominated compound. Mixture of chloroform and acetic acid seems to give many products (4 position brominated)...

So is there a nice way to brominate thiophene with electron withdrawing group attached at the 2/5 position?

[orgopete]

Bromination of this is rather tricky as bromine at room temperature does not work due to the strong electron withdrawing group. Refluxing in chloroform form the 5,5'-dibromo product but reaction doesn't seem to go into completion even at 3 equivalence of bromine. Monobrominated compound is observed, with the presence tribrominated compound. Mixture of chloroform and acetic acid seems to give many products (4 position brominated)...

So is there a nice way to brominate thiophene with electron withdrawing group attached at the 2/5 position?

I think that is correct. Thus:

Yu. D. Churkin1, L. V. Panfilova1, V. D. Lugovoi1 and N. V. Boiko1

(1)    V. V. Kuibyshev Kuibyshev Polytechnic Institute, 443645 Kuibyshev
Received: 17 June 1980 

Abstract  The nitration of 2-formylthiophene, 2-acetothienone, and unsaturated ketones of the thiophene series with copper and aluminum nitrates in acetic anhydride at various temperatures was studied. At low temperatures 2-acetothienone gives a mixture of 4- and 5-nitro isomers, while 2-formylthipphene gives only a 5-nitro-substituted compound in the diacetate form;

I also found thiophene-2-carboxylic acid was nitrated at C4.

Okay, alternate route? I presume your thenil comes from oxalyl chloride? If so, then reverse some steps. Prepare 5,5-diaminothenil from 2-acetamidothiophene and Friedel Crafts. Diazotize it to make the bromide. (See Thiophenes, Salo Gronowitz, p. 532 esp ref 480. I accessed this via Google Books.)