Emerging data on properties and pharmacophore of DRIs

[aced126]

Hmm, I'm not so sure T-butyl metabolises in the same way (or proportions) to toluene. Toluene has a benzylic carbon which can form a stable benzylic carbocation making hydroxylation at that carbon much easier than just any old carbon. The benzylic carbon in t-butylbenzene is tertiary and cannot be oxidised. The other carbons have no sort of stabilisations, and will all have to form primary carbocation intermediates (very unstable). In fact, it might even be more carcinogenic than benzene, because it has an activated ring more prone to epoxidation.

In the link you posted, as you can see M12 is a competing metabolite (which I'd guess is formed in greater proportions to M4 and its metabolites), which probably results due to the ring activation via conjugative stabilising effect of the ether.

 

[Friman1987]

Yes, it is possible that it will metabolized as you say. But i dont think it is more carcinogenic than benzene.
According to the following article the oxidation stops after C-hydroxylation:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1216106/?page=3

It might be something like that:

Time to sleep.
Good night friend.

 

[aced126]

Hmm, yes, conjugation seems to be less sterically hindered than further oxidation.