[kekule]

I am trying to react an aldehyde (formaldehyde) with a primary amine (l-lysine) to yield an imine adduct.  Water is a by-product, and removal of water yields the imine.  I assume water as a solvent should be avoided, since imines are easily hydrolysed.  My problem is, l-lysine seems to be insoluble in everything EXCEPT water!  Formalin also contains water, but I can get around this by generating formaldehyde gas.  Any suggestions as to how to perform this condensation without water?

Thanks

[HP]

Mannich bases (formimimines) are stable in water aducts and not as Schif's bases in equilibrium with water aducts so i think theres no problem

[kekule]

I want to isolate the intermediate iminium salt and not continue with the Mannich reaction where a ketone is involved.  Any ideas how to successfully do this are appreciated.

[movies]

I spent a lot of time trying to isolate imines.  It's not all that easy in a lot of cases.  Sometimes you can remove the water with a Dean-Stark trap.  You're in a tough spot with the amino acid thing though.  They aren't soluble in much.

[kekule]

Movies,

Is it possible for me to freeze dry the solution to remove the water?

[movies]

At low temp you might have a problem with formaldehyde solidifying into polymers.

I haven't seen freezing used as a method of removing water from solutions, but I suppose it might be possible.

[HP]

Yes movies is right: at the begining of 20th century Lebedev obtained hexamethylenetriamine(urotropin) by vacuum evaporating equimole formaline/amonia mixture...You may try freezedrying with lyzine and formaline hm, may be interesting rezults you'll obtain and hope no poliformaldehyde form Write us please...

[kekule]

In trying to isolate the lysine-formaldehyde iminium salt, I added absolute EtOH to the reacted aqueous solution.  Because the iminium salt is insoluble in EtOH and very soluble in water, and because water and EtOH are miscible, the salt?? fell out of solution, and was filtered.

Are these crystals the iminium salts?

The first reaction I performed at room temp.  This yielded the crystals I mentioned in the above paragraph.  

In my second attempt, I held the temperature of the solution at 37 celsius for two days.  Addition of EtOH to this solution yielded a sticky yellow mass!?  What gives?  SHould I keep this type of Mannich reaction at cooler temps??

Any suggestions greatly appreciated!

[HP]

I think you have succeed in isolathing the desired product as precipitating it with ethanol. What kind of lyzine you use : i mean free aminoacid or its hydrochloride? The yellow colour of your product seem to be iminium aduct because i have some experience with Schiff's bases many of which are similar coloured... You may do IR analyze your product to see the characteristic pick for N=CH2 and compare it with your pure lyzine. That what i can help you now Whish succes!
P.S. Whats the synthetic purpose of your desired product?