Anyone got any experience with Ariadne synthesis? Or other 4C compounds?

[Rabidreject]

So iv been eyeing this compound for a while now (Ariadne) or other related 4C compounds.
I found some nitropropane, well, somewhere to get it at a reasonable price, has anyone done any chemistry in this area?
I have experience with other more standard phenethylamine’s and amphetamine’s and I wonder if it’s much harder or different to that area…

The experience reports of the 4C compounds look interesting.

Is it likely to be a similar case to the 2c and Dox compounds in that, people tend to use the 2,5-DMOaldehyde before adding anything to the 4 position, make the nitrostyrene and then reduce and THEN do the halogination? Where as with the alkylation, it seems people add the alkyl group to the 4 position to the disunited aldehyde first and then proceed with the Henry and reduce.
I hope that makes sense…it does in my head but words I am not good with words.

Anyway yeah if anyone has looked into this in more depth than me please chime in coz it sounds like a cool project.

 

[Rabidreject]

To say it more concisely - can I treat the synthesis of the haloginated 4C compounds as analogous to the haloginated 2c or dox compounds? Boom. Words are my friend again ha

 

[i_can_see-you_can_not]

The condensation reaction of benzaldehydes with nitropropane takes much longer than with nitroethane, in my experience like 5x longer. Monitor reaction progress with TLC, dichloromethane is a suitable quick-and-dirty eluent. The spot of the nitrostyrene will occur above the aldehyde and should be visible due to its yellow or orange colour. Yields are typically a little bit worse than with nitroethane too.

The NaBH4/Cu can sometimes stall on these substrates, so it takes some optimising depending on the exact substrate you are working on. Don't expect stellar yields right from the beginning and take time to try it multiple times on small scales.

Upon bromination, both DOB and 4C-B have a tendency to not crash out of AcOH as simply as 2C-B. Adding ether or EtOAc after full conversion can aid with that.

 

[Rabidreject]

Legend. I was sure someone would have worked on these!
Yeah I guess that does make sense with regard to nitropropane being less reactive, as nitroethane is compared to nitromethane. This may explain my slightly lower yields making nitropropene’s compared to nitrostyrene’s of the same substitution pattern actually - now I think about it.

Okay yup TLC will be used yeah. And useful into regarding using an anti-solvent. I actually had really bad luck when I ran the 2c-b bromination in GAA using Br2. It just refused to crash out and obviously cooling GAA isn’t going to help much. I think I ended up distilling off most of the GAA and doing a b/a on it in the end. I guess adding an antisolvent there would have saved me a whole lot of time! Ha