Chemistry of 3-Bromopyruvate

[3bromopyr]

Recently much interest has been generated in 3-Bromopyruvate as an anti-cancer therapy.

 

Could someone explain the chemistry behind the synthesis of 3-Bromopyruvate?

This url gives 5 ways of making 3-BP.

 

http://www.molbase.com/en/synthesis_1113-59-3-moldata-8403.html#tabs

 

It appears that bromine displaces a methyl group in four of the synthesis reactions.

Is this correct? If so, why would this be so.

 

The full reaction given notes some of the reactions produce secondary products (for example, the reaction with

water also produces tri-bromopyruvic acid). What might some ways to purify the synthesis from these chemicals?

 

[John Cuthber]

In reactions like this the bromine doesn't replace the methyl group, it replaces one of the hydrogens of that group.

The kink in the line to the Br is a methylene group. unhelpfully, they also flipped the molecule right to left which makes it less clear.

 

 

[3bromopyr]

Thank you very much for your reply.

 

Any further explanation for why the bromine replaces the hydrogen in the methyl group would be appreciated.

Would it be that methyl groups do not have strong bonds between the carbon and hydrogen, so that the bromine

can displace a hydrogen? {I am not sure of the terminology, though would that make the hydrogen the leaving

group?}

 

Why is one of the other groups not displaced by bromine (for example, the hydrogen on the hydroxyl group {possibly because the oxygen is holding it so strongly?} )

 

I am also interested in some of the other synthesis pathways. In these other reactions (for example, the one starting with 123-54-6 not only produces 3-BP, but also 3,3, dibromo-2-oxopropanoic acid and tribromo-pyruvic acid. These other products have 2 and 3 bromines that have replaced hydrogens in the methyl group.

 

Full details of the reaction above with 127-17-3 were not given, though the molbase website noted that only 89% of the reactant produced 3-BP. What other products would have been produced? Why wasn't the bromine source clearly identified in the reaction?

 

It seems surprising in the synthesis route with H20 that the main product appears to be 3-BP. I wonder why the 2 bromine replacement in the methyl group would not be more favored, as the reactant is diatomic bromine.