[HailoMan]

Hi all,

I am currently trying to synthesize amine-terminated bifunctional polyethyleneglycol (PEG) from PEG.
It seems like the most commonly used lab-based synthesis routes are:
1) Gabriel synthesis: Hydroxy-halogen-exchange, followed by reaction of the primary halide with phthalimide and subsequent hydrazinolysis (http://en.wikipedia.org/wiki/Gabriel_synthesis)
2) Mitsunobu reaction of the primary alcohol using hydrazoic acid HN3 as a nucleophile, followed by reduction of the alkyl azide (http://en.wikipedia.org/wiki/Mitsunobu_reaction)

The problem is, I don't think my lab is quite well-equipped to deal with the two routes because of obvious hazard with hydrazine or DEAD (or thionyl chloride if I use the chlorination route).

So just wondering if there are safer methods out there that are also relatively straightforward.

I'm not sure how practical it is to oxidise the terminal hydroxyl group to an aldehyde before following that with reductive amination?
I feel like this might avoid the need for any nasty halogenated molecules.

Introducing the aldehyde group seems fairly straightforward.
From Brooks & Harris (1984): PEG mixed with using activated DMSO (acetic anhydride in DMSO) using methylene chloride as solvent for 30 h at room temperature. They then used diethyl ether to precipitate the resulting aldehyde-terminated PEG. There are probably other safer alternatives to diethyl ether, but seeing that it's run at room temperature, it's not too bad.
The reductive amination is probably the more challenging part. Looking around, Leuckart reaction which uses ammonium formate seems like a very simple option, though I'm not too sure about the yield.

Any advice would be much appreciated.

[vickyvail]

check this paper,  Org. Biomol. Chem., 2013, 11, 1116
good luck!

[kriggy]

Im not sure what hazzards you mean by using DEAD / DIAD, obviously there are some dangers associated but  are quite safe from my experience compared to other stuff you can meet in a lab. Of course it depends on what is the amount of given compound that you need. Some of my friends do lot of mitsunobu and also used hydrazine and I dont think our department has any special equipment that was needed for that.

If you dont want to do gabriel synthesis, then you might opt for delepine reaction

[zelenchukta]

Not sure how much volume you need, but if small, it may be much easier to purchase some:

http://www.sigmaaldrich.com/materials-science/material-science-products.html?TablePage=20330418

[clarkstill]

If you dont want to do gabriel synthesis, then you might opt for delepine reaction

10 years in chemistry and I've never seen that reaction before, pretty neat though!