Picric-A - 15-1-2010 at 09:59
Does anyone know any viable routes to this starting compound?
I am trying to make chloroprocaine and this is the starting reagent.
I would guess chlorination of 4-Aminobenzoic acid or chlorination of toluene followed by the usual synthesis of PABA.
Any help would be appreciated.
Jor - 15-1-2010 at 10:40
Can't you chlorinate p-nitrotoluene, followed by oxidation of the methyl with permanganate, and then reduction with dithionite?
Only problem is, I'm not sure if the main product is the right isomer, so with Cl on 2, and I;m also not sure if no benzyl/benzal chloride is formed.
Nicodem - 15-1-2010 at 11:04
Yes Jor, the electrophilic chlorination of p-nitrotoluene does give 2-chloro-4-nitrotoluene. However, chlorine alone can not achieve this because this
substrate is quite unreactive toward electrophiles. Thus you need a more electrophilic reagent, for example trichloroisocyanuric acid in conc. H2SO4
would come in mind for an amateurish solution.
Literature examples use either non friendly conditions like Cl2O/H2SO4 or Cl2 in the presence of Lewis acids with biarylsulfide cocatalysts (see for
example EP399293 or EP1078914).
Edit: I think that if just a Lewis acid without a tioeter would be enough, then there would be no use in adding a biarylsulfide and there would be no
point in writing those patent. Perhaps the Lewis acids are more able to activate S-chlorosulfonium chlorides than they are able to activate elemental
chlorine. But then again I don't have the time to read these patents.
[Edited on 15/1/2010 by Nicodem]
Picric-A - 15-1-2010 at 11:10
Thanks for the responses.
I thought some benzyl/al chloride would form... what about using AlCl3 + Cl2? this will work for benzene + Cl2.
TCCA + H2SO4 sounds simple, thanks,