Sciencemadness Discussion Board

drying methylammonium acetate

stoichiometric_steve - 23-3-2007 at 12:50

reacting 40% by weight aqueous methylamine solution with glacial acetic acid produces a liquid form of methylamine which, as it seems, is impossible to dry and crystallize.

does anybody know of a method by which this could be accomplished?

azeotropic drying with toluene has already been tried out, a lot of water came over, but no crystallization set in. in fact, the liquid is still very far from being viscous.

thanks!

Shaddy - 23-3-2007 at 13:45

I suppose it will be easier to start with dimethylamine-gas than to get out salt from your mixture.
You can try dry ethanol.. may be, at least it should be better as toluene.

Otherwise:
"Methylammonium acetate was formed in either of two ways. The first involved sparging methylamine gas through a solution of 50 mL of acetic acid in 150 mL of diethyl ether at 0.degree. C. When precipitation of the product was complete thesolvent was removed in vacuo and the residue used without further purification."
You can replace ether with any other solvent that miscible with acetic acid.

[Edited on 23-3-2007 by Shaddy]

stoichiometric_steve - 24-3-2007 at 05:39

maybe i should have mentioned that using methylamine gas is out of the question.

not_important - 24-3-2007 at 07:39

The azeotropic toluene should have dried it, the problem I see is the possibility of splitting the salt back to acid and amine (there's your methylamine gas) which you would have smelled. Excess acetic acid would come over with toluene at 100 to 101 C.

I've dried solutions of quaternary amine salts using toluene as you did. With one case the salt solution formed gummy balls of water and the salt, adding alcohol to the toluene and taking off the tert azeo solved that after which most of the alcohol was distilled off and the salt crystallised out.

stoichiometric_steve - 25-3-2007 at 08:50

Quote:
Originally posted by not_important
the problem I see is the possibility of splitting the salt back to acid and amine


how would that happen? and what would be the remainder (which is in my case a faintly yellow liquid)?

Nicodem - 25-3-2007 at 09:06

Another likely problem is also the condensation to N-methylacetamide which happens quite slowly, but nevertheless, already if you heat above 100-110°C for a prolonged time and moreover remove water by azeotrope. This side product would prevent the crystallization of the salt.

bubbleboy - 26-3-2007 at 22:59

What about slight heating under vacum?

not_important - 27-3-2007 at 02:23

You are dealing with a weak acid and not very strong base, they can part ways with the more volatile base vaporising leaving free acetic acid. The free acid could coat the salt, dissolving some of it.

As the acid is fairly volatile too, it could boil off in its azeotrope with toluene, leading to the slow lose of product during drying.

As Nicodem said, if some dehydration to the amide occurred, you'd get yey another impurity that could lead to gummy, 'wet', or even oily product.

On the other hand, toluene is a decent solvent for acetic acid and will dissolve some acetamide, more of a substituted one, so small amount of those are likely to say in solution; that would make them less of a problem.

I would have attempted to find solubilities in differing solvents and try crystallising from solution. Ketones and esters likely aren't good choices, because of potential reactivity problems. I would have tried toluene with ethanol or isopropanol, dried before hand by azeotropic distillation of the mixed solvents, adding enought to just get the product into solution at boiling, azeotrope off any water, and allowing that to slowly cool in a flask closed with a drying tube; refrigerate after it sat a day or so.

Some salts are very hard to get to crystallize when made by aqueous methods, you can't get them dry without causing decomposition. In those case dry routes are your recourse, which often means using gases.

Klute - 27-3-2007 at 03:48

Is the acetate salts really necessary? Can't you replace it by another, more practical one?

stoichiometric_steve - 27-3-2007 at 04:56

the acetate is needed for a reductive amination. of course, the benzoate or tosylate would also work, but then again, i dont have those acids.

i'm going to use metathesis from methylamine HCl and potassium acetate in MeOH, since i dont have methylamine as a gas.

not_important - 27-3-2007 at 14:47

Does it need to be absolutely dry? A trace of water will prevent crystal formation, as water is formed in the reduction it shouldn't be a problem.

stoichiometric_steve - 28-3-2007 at 10:22

Quote:
Originally posted by not_important
Does it need to be absolutely dry? A trace of water will prevent crystal formation, as water is formed in the reduction it shouldn't be a problem.


i guess it doesnt. then again, the acetate is also a wonderful catalyst for henry reactions, in which i got best yields when using dry MeNH3OAc in MeOH.

Klute - 28-3-2007 at 13:32

Well why don't you simply dissolve the uncrystallizedd amine in solvant (you'd be using alcohols, no?) and dry the solution with silica or a suitable strong enough dissicant? I was thinking of CaO at first but I guess that would basify the amine salt....

Or maybe put your "liquid salt" in a CaO/NaOH dissicator with some vaccum and forget it a day or two... should get it dry...

Oh, and by curiosity, is it a triacetoxyborohydride reduction?

[Edited on 28-3-2007 by Klute]

[Edited on 28-3-2007 by Klute]

stoichiometric_steve - 29-3-2007 at 10:10

yes i am thinking about STAB (sodium triacetoxy borohydride) for the imine reduction. any hints there, klute?

bubbleboy - 29-3-2007 at 11:14

Steve, you're making things way too complicated for yourself. Imine formation in non-polar solvents is extremely slow (refering to triacetoxyborhydride reduction) and may take up to a couple of days. Then the reduction, another day.
Make the hydrochloride salt of the amine. Mix equimolar amounts of the HCl salt and triethylamine freebase in methanol. Add your ketone and let stir for an hour, allowing for the formation of the imine. Then proceed to reduce with plain old borohydride. 6 hours total.

stoichiometric_steve - 29-3-2007 at 23:02

thanks, bubbleboy! what substrates have you tried this for? i have heard that the method you proposed didnt work for plain phenylacetone, according to a fellow researcher.

i wasnt going to form the imine in a NP solvent but in MeOH and add that to a solution of STAB in toluene.

some refs say that an equimolar amount of acetic acid catalyzes imine formation and reduction, too, when using ketones.

Klute - 30-3-2007 at 10:55

I'm not too sure about the stability of phenylacetones imines, didn't find alot of info on that, but what I have seen in a few procedures involving aromatic amine ( =>stabilized imines) was to form the imine in anhydrous alcoholic solvant, with dissicants, then stripping the MeOH under vacuum leaving a concentrated solution of the MeOH, and then toluene is added to obtain a MeOH-containing NP if using preformed solid NaBH(oAc)3 (those bastards.. can get whatever they want..), or adding the MeOH solution of the imine to a suspension of the triacetoxyborohydride in toluene, THF, etc made from NaBH4 and AcOH.... I also read somewhere that excess AcOH help reductions.. Hard to see if the vacuum distillation of the solvant would degrade the preformed imine... I guess only GC analysis could determine that...
NaBH(OAc)3 seems to be a much more safe substitute to NaBH3CN, with the same advantage that its much more selective to imine reduction, leaving the ketone alone... One the other hand, it degrades in contact with water, so it can't be used in "wet" medium The problem when having only limited supply of NaBH4, is that you need 4x the amount of NaBH4 for the same amount of imine, as 1 mol of NaBH(OAc)3 releases only 1 mol of H-... because NaBH3(OAc), NaBH2(OAc)2 can't be isolated at room temp... So depending on which is more available, the ketone or the hydride, its worth it - or not.

A very interesting route to explore, would be to perform the reduction in GAA, there's a pdf at Rhodium's discussing this for ketone reductions, they add the NaBH4 to the ketone dissloved in GAA.. If this could be applied to an imine reduction, it would greatly simplify things... The question is how would the imine formation proceed in GAA... Would the methylammonium acetate be as effective as it's freebase? Imine formation are catalysed by acids such as PTSA in differents procedures, but in such acidic medium? The water formed should of course be removed...

Bubbleboy, when you say that imine reduction is extremly long in NP solvants, does that also include using a Dean Stark with toluene, at reflux?

Stoechiometric_Steve, where did you find a ref to Methylammonium acetate in red.amin, or did you simply consider that as ammonium acetate works for primary amines, the methylamine salt should work too?

[Edited on 30-3-2007 by Klute]

stoichiometric_steve - 30-3-2007 at 11:18

Quote:
Originally posted by Klute
Stoechiometric_Steve, where did you find a ref to Methylammonium acetate in red.amin, or did you simply consider that as ammonium acetate works for primary amines, the methylamine salt should work too?
[Edited on 30-3-2007 by Klute]


i have never seen any reductive aminations involving ammonium acetate and sodium borohydride.

Klute - 31-3-2007 at 13:31

Quote:
Originally posted by stoichiometric_steve
i have never seen any reductive aminations involving ammonium acetate and sodium borohydride.


Sorry, should have mentioned with NaBH3CN or NaBH4/Ti(IV)isoproproxide... Barium wanted to give a try with conc.NH3 and a PTC, never seen any reports so don't know if he ever tried it... I had this impression I read about it somewhere, but just can't figure out where.. or maybe I'm just confusing with the cyanoborohydride or using the Titanium isoproproxide...

So where did you get the idea of using MeNH3.OAc?