Piperonal Routes?

[CryoThio]

I'm trying to see if there are other ways to get to mdp2p from piperonal.

Obviously, there is nitroethane. It's hard to get, so not the best option.

I don't think the route through MEK works on piperonal, never seen it claimed it does. Might be a decent option if so though.

Then there us the darzens. Not bad, things have to be dry apparently, and cold, but otherwise things are too difficult.

Are there any others that I am missing?

 

[Germanium]

To a 500ml rb three-neck flask with a thermometer and a stir bar was added 16,6g (100 mmol) 2,5-dimethoxybenzaldehyde and 18,3g (150mmol) methyl 2-chloropropionate. 100ml MeOH was added to get the benzaldehyde into solution. While keeping the reaction mixture at 15 deg C, 8,1g (150 mmol) sodium methoxide in 50ml MeOH was added dropwise during 40min. When all alkoxide was added the reaction mixture was allowed to come to room temp and stir for another hour. The reaction mixture was then added to 10g (250 mmol) NaOH in 40ml water while keeping the temp at 20 deg C, then all was stirred at room temp over night. The next morning there was a thick white precipitate in the solution. To this 15% aq HCl was added until pH 3,5 was reached. This caused a clear yellow oil to fall out. The solution was heated on a waterbath at 65 deg C for two hours to complete the decarboxylation. The methanol was removed by distillation in a rotovap and the ketone was isolated by steam distillation. The distillate was extracted with 3x75ml toluene and the collected toluene phases dried over MgSO4. The toluene was removed by distillation in a rotovap leaving a clear yellow oil.

Yield: 14.94g (76,9 mmol) 2,5-dimethoxyphenylacetone
Purity: 96% by HPLC



I believe mdp2p can be synthesized by using piperonal instead of 2,5-dimethoxybenzaldehyde.

 

[arundo]

I was thinking the same days ago, about piperonal+mek to do an aldol condensation, then oxidate the intermediate with H2O2 or classical twodogs.

I tried to do a simulation with some reaction free engines and said would be possible, with a confidence of 0,41