The Hive > Serious Chemistry

Ring opening of aziridine with PhMgX

(1/3) > >>

Rhodium:
If ethylene oxide is treated with phenylmagnesium bromide and hydrolyzed, 2-phenethylalcohol will result.

What if one treated N-tosyl-aziridine* with phenylmagnesium bromide? Would 2-phenethylamine result directly after the hydrolysis? If so, then we have a GREAT novel route to all our favorite phenethylamines...

*Aziridine is the nitrogen analog of ethylene oxide, and it needs to be protected with tosyl, or the grignard will be quenched.

http://rhodium.lycaeum.org

oxycodfish:
Thank goodness for ring strain!  Looks like a good possibility, at least based on my unexpert estimation.  Yields for the closest analog I could find to this aziridine reaction are around 60%, couldn't find any actual *quantitative* data on reaction rates though.  Then again, I'm currently library-less and journal-less, so my search capabilities aren't what they used to be.  Hopefully this situation will be rectified soon.  I'm rambling -- in any case, I'll be interested to hear any results (theoretical or empirical) in this line of research.

jim:
A classic way to get around the quenching of the Griganrd reagent by the desired end product is reverse addition.

That is, slowly add (AKA drip) the Grignard reagent to the vat of the compound to be acted upon.  The Grignard reacts with the most availible substance, which is usually the starting compound, and not wit the end product.  In this case that might be a little hard however, because I believe that Aziridine is a gas at room temperature, but I could be wrong.  Even if the Aziridine is a gas one could dissolve the Aziridine in an inert liquid.

AS A CRAZY SIDE NOTE:  I recently discovered that poly(ethylene glycols) can be very easily ETHERIFED, that is @ room temperture, with KOH (and maybe NaOH), and an alkyl halide, the poly(ethylene glycol)'s OH groups can be can alkylated creating ether.  Perhaps the etherifed poly(ethylene glycols) can be used as solvents for Grignard reactions since they are close analogs to ethyl ether, are known to coordinate well with metal ions, and are at the very least totally inert to Grignard compounds. 

What do you think?

Rhodium:
Tetrahedron 53(13), 4935-4946 (1997) (https://www.thevespiary.org/rhodium/Rhodium/pdf/aziridine/phosphorylaziridine.grignard.pdf)

The above is an article about exactly this reaction. They used the diethylphosphite protected 1-methylaziridine, and got the ring-opened product in 87% yield, and after hydrolysis they isolated about 30% amphetamine (on a 0.03 mole scale, it should be better on a larger scale).

Greensnake:
Yeah, this route is fairly doable. I faintly recall that copper modified lithiumorganics were used and probably this must work with Grignards too. Ok, it's good idea for research purposes, but GOD FORBID anybee tries to mess with aziridines at home. Aziridine is toxic, carcinogenic and what else, and in some aspects make potassium cyanide look like innocent food additive.

Navigation

[0] Message Index

[#] Next page