[tsam3314]

Hi,

Can someone please tell me if this synthesis will (theoretically) work? I'm sure about most steps, just not about the internal SN2 reaction i've marked. In particular i'm sure about the sterochemistry or the products.

I was also wondering if for the aforementioned reaction i should use thionyl bromide/iodide to create a better leaving group? I'm trying to force the fromation of a ring as I know amides are generally unreactive, but this is the only scheme I can think of and apart from this one step, it works!

http://img25.imagevenue.com/img.php?image=09909_pzq_synthesis_122_1071lo.JPG

Thanks

[refid]

Your dicyclohexylcarbodimide step... i think its better mayb convert the alcohol to acyl chloride to close the ring..i dunno just a guess

[tsam3314]

yeah you can do both, it just that i know dcc will work without any side reactions, that's all. I was interested in problems with the other steps - did you see anything wrong with them?

[Custos]

The medium ring closure might be a problem. The internal SN2 will also be difficult but possibly aided by the fact that the chlorine is activated by the nitrogen (neighbouring group effect).

Do you have to come up with a novel route? There's lots of stuff around on this compound, eg. http://etd.fcla.edu/SF/SFE0000266/Thesis.pdf

[tsam3314]

yeah it has to be our own route. I was thinking of using thionyl bromide instead of thionyl chloride. One other thing i found was that the formation of the ring (a 6-exo-tet) is favourable according to Baldwin's rule of ring formation.

also anyone know where i can find information (like the eudismic ratio) on praziquantel

thanks

[ximik]

I don't think you can invert the stereochemistry during the reaction with SOCl2 because of the participation of the neighbouring nitrogen

[Wisemanleo]

I like the idea of thionyl bromide, since its bigger and would serve as a better leaving group.

As for the internal SN2 reaction, what reagents have you considered?

[Custos]

Rather than use thionyl chloride or bromide how about forming the mesylate or tosylate (or even triflate) directly from your alcohol?