simple preparation for iminium/eschenmoser salts for the mannich

Ok, since this is a very useful compound for the mannich reaction it might be useful for others, there is barely anything reported on it.
I think I got five hits for the search term eschenmoser only here, so I'd like to show what I got, including what I did wrong and where to improve it.

Its the reactive species in the mannich reaction but isolated and thus works much better and faster, even on sterically hindered substrate without forcing conditions, and merely takes a few minutes with nonhindered ketones.
The dimethylamine can be replaced with others, I've tried the same with pyrrolidine too and it worked just the same, and I've even seen asymmetric versions(e.g. N-methylethylamine for example) being used in some quite recent thesis about psilocybin analogues.

What I did was, just to follow that orgsyn procedure for the preparation of the 1,1,2,2-tetramethyldiaminomethane, under notes 2.: http://www.orgsyn.org/demo.aspx?prep=CV5P0434
Since I didn't need to isolate that by distillation, I skipped that, to avoid the nasty lachrymatory effects of it.
I just pulled it into two portions of diisopropyl ether, then washed and dried that.

This diamine will then react with one equivalent of acetyl chloride in this ethereal solution, giving one equivalent of dimethylacetamide and one of the iminium chloride salt which precipitates.

The attached paper describes the use of this iminium salt for the mannich reaction, even on sterically hindered substrates like isobutyrophenone.

I made a few mistakes though, when I realised that my salt still had residual acetyl chloride on it, I immediately washed it with a little bit of.... acetone... half of my salt got pulled through the frit and reacted in consequence... if I had just use THF, I could have recovered that all

I just copy from another forum what I did:

Quote:

I used -9g PFA(0,3mol) to prepare a formaldehyde solution in 80ml of water, and -49g of dimethylammoniumchloride(0,6mol) in water(I haven't noted the exact volumes of both solutions before freebasing them...), which was freebased with an aq. solution of -24g of NaOH(0,6mol), and in the end I had a solution of 180m containing ~27g of dimethylamine(still 0,6mol :). The dimethylamine solution was dropped to the ice-cooled PFA solution over the course of an hour, and then left to stand for an hour at RT. Then, cooled down again, and then, sodium carbonate was added, an excess, around 2-300g, to precipitate the oily tetramethyldiaminomethane, which worked great. That stuff was extracted with 2x50ml portions of DIPE, then washed and dried. The DIPE solution was then cooled down and to that stuff, slowly 19,4ml of AcCl(0,224mol) were added to it(very exothermic), resulting in the immediate precipitation of böhmes salt. Now, since it was said that this stuff is very deliquescent, I wanted to work as fast as possible. So an hour after the acetyl chloride was added, I set up for vacuum filtration and quickly filtered the stuff out, washed it with another 10ml of DIPE... and crap, then I was out of DIPE. I could have used THF(but I know its sparingly soluble in it), so I used 2x20ml portions of acetone to wash the last residual acetyl chloride out... which worked well. Ok, so now I had the slightly damp, DIPE smelling solids and quickly deposited them into a container, which I closed immediately. The yield was 15,64g of böhmes salt(114,4mmol, but calculate the lousy percentage yourself). One of the worst things was, that after the filtration, AFTER I used acetone for the washed, lots of more böhmes salt precipitated in the filtrate... especially bad, because it will react with the acetone now, and what the hell am I going to do with a-dimethylaminomethylacetone? But take those anecdotes as helpful advice if you're going to play with the mannich and the "mannich wunderwaffe" that both böhme's and eschenmosers salt represent.

Fantastic
I shall be trying this myself some time soon.
Its nice to see that the dimethylamine can be made in situ from the hydrochloride, I thought maybe any excess NaOH would interfere with the reaction somehow
Certainly a lot easier than bubbling the gas through water to make a solution!

Do you suppose the N,N,N,N-tetramethyldiaminomethane is stable enough to make and store? I don't see why not really; I still haven't made the acetyl chloride yet for making the iminium salt.

Thank you for all these awesome enlightening posts, here and elsewhere! <3