Methylamine hydrochloride synthesis. Large scale.

[FENTAMAS]

@Frit Buchner, this synthesis is over a century year old (Marvel et al., 1923, Org. Synth.) and confirmed to be working by many independent chemists, including me.
Moreover, every publication in that journal should be peer reviewed, so it is one of the most trusted source for practical organic chemist.
Link for the original document - https://www.orgsyn.org/demo.aspx?prep=CV1P0347
If you fail, then you definitely doing something very wrong or your reagents are not what you expect it are.

Chloroform could be substituted by DCM, but anyway it is not necessary.
If you want good results better to use paraformaldehyde, not formaldehyde with methanol, the more MeOH the more colored RM in my experience.
Without methanol you not need to distill reaction mixture, just hold temperature below 100C, it works even at lover t, just take more time.
You absolutely need aspirator vacuum for distilling portions of water if you want nice white product.
The key for a good purity is fractional crystallizations, the more the better result.
I used 5-6 times, a little bit more than in the original procedure and got fantastic results.
So after 6+ hours of 100C, distill some water under vacuum, cool down, suction filter, and repeat.
First 2-3 fractions will be ammonium chloride. Then methylamine*hcl with crystal structure clearly different from first batches, more like hygroscopic shiny flakes.
The last mother liquor will contain mostly dimethylamine*hcl and should be discarded if don't need it.
The final step is multiply crystallization from hot abs. ethanol or methanol as described. But it also is not necessary for many synthesis, it just for removing last traces of water, NH3*HCl and Me2NH*HCl.

So as you can see it is time consuming, many days of working, but you can start with pretty large batch and prepare non-trackable pure Methylamine for month or years.

 

[Frit Buchner]

@Frit Buchner, this synthesis is over a century year old (Marvel et al., 1923, Org. Synth.) and confirmed to be working by many independent chemists, including me.
Moreover, every publication in that journal should be peer reviewed, so it is one of the most trusted source for practical organic chemist.
Link for the original document - https://www.orgsyn.org/demo.aspx?prep=CV1P0347
If you fail, then you definitely doing something very wrong or your reagents are not what you expect it are.

Chloroform could be substituted by DCM, but anyway it is not necessary.
If you want good results better to use paraformaldehyde, not formaldehyde with methanol, the more MeOH the more colored RM in my experience.
Without methanol you not need to distill reaction mixture, just hold temperature below 100C, it works even at lover t, just take more time.
You absolutely need aspirator vacuum for distilling portions of water if you want nice white product.
The key for a good purity is fractional crystallizations, the more the better result.
I used 5-6 times, a little bit more than in the original procedure and got fantastic results.
So after 6+ hours of 100C, distill some water under vacuum, cool down, suction filter, and repeat.
First 2-3 fractions will be ammonium chloride. Then methylamine*hcl with crystal structure clearly different from first batches, more like hygroscopic shiny flakes.
The last mother liquor will contain mostly dimethylamine*hcl and should be discarded if don't need it.
The final step is multiply crystallization from hot abs. ethanol or methanol as described. But it also is not necessary for many synthesis, it just for removing last traces of water, NH3*HCl and Me2NH*HCl.

So as you can see it is time consuming, many days of working, but you can start with pretty large batch and prepare non-trackable pure Methylamine for month or years.

FENTAMASI followed the original synth the first time and I the second time I followed one I was given by one of the experts here. I refluxed under vacuum for 4 hours and distilled under vacuum for 2 hours. The temps never Reached the target level though, perhaps my vacuum is stronger than they were using in 1910. That's what I assumed.The second time the methylamine hcl and the product I made with it looked exactly like everyone's pictures the methylamine hcl even produced flammable gas when neutralized with NaOH and water. But the product has no cns action.
I have here a liter of technical grade formaldehyde with 5%methanol and I'm going to try again but do I need to distill the methanol off to start? I'm going to read some more, it's true my ammonium chloride is fertilizer grade not technical grade could that be the problem? How do you decide when "a round" of reducing the volume of the rm is done? I was measuring it and stopping every time I halved the volume but only get 4 rounds that way and 4 batches of crystals. Would the methanol I use at the end not being dry enough cause it? I can't imagine that was the problem though because I distilled it twice and put in 100% w/w, 3a sieve for several days

 

[FENTAMAS]

There's a large advantage in refluxing under vacuum in that the ratio of monomethylamine to di and trimethylamine is much higher as outlined in
Jones, H. I., & Wheatley, R. (1918). THE PREPARATION OF METHYLAMINE. Journal of the American Chemical Society, 40(9), 1411–1415. doi:10.1021/ja02242a007
10.1021/ja02242a007
Highlights include;


tabulation of results brings out several facts clearly:



Link to the document

Frit BuchnerThat effort do not worth it.
And that's just authors' speculation about vacuum, which itself likely cannot influence selectivity, as is with formic acid excess too.
Maybe it is just effect of reduced temperature, more effective stirring of RM by bubbling and more full conversion of NH3*HCl, etc.
Later authors don't use vacuum reflux, moreover it is quite uncommon method even nowadays.
Reduced boiling temperature also will be in the case of excess of MeOH in formalin, because of esterification of formic acid and forming low boiling methyl formate and other by-products, but as I already noted, try to avoid it.

 

[Frit Buchner]

That effort do not worth it.
And that's just authors' speculation about vacuum, which itself likely cannot influence selectivity, as is with formic acid excess too.
Maybe it is just effect of reduced temperature, more effective stirring of RM by bubbling and more full conversion of NH3*HCl, etc.
Later authors don't use vacuum reflux, moreover it is quite uncommon method even nowadays.
Reduced boiling temperature also will be in the case of excess of MeOH in formalin, because of esterification of formic acid and forming low boiling methyl formate and other by-products, but as I already noted, try to avoid it.

FENTAMASThat's a fair point. I'll have to read it again with that in mind (that the vacuum lowers the temperature and makes the stir bar turn easier, ect.) This document was linked to me by one of the site experts so I didn't scrutinize it heavily. Even if I decide it isn't proven that the vacuum itself is the reason they achieved a higher yield I might decide that the cause doesn't matter and the effect does. We consider gravity and magnetism effect and plan for it every day even though the mechanism is debatable. Buying formaldehyde is stressful because I'm not a taxidermist or farmer. I have more spare time than money or bravery to buy formaldehyde without a legitimate use. It's not free. I'll probably choose to maximize my yield over convenience. I'll have $33 in this formaldehyde whether I get a kg of methylammonium chloride or a gram from it. It can't be bought legally here and there is no end to the amount I can use

 

[FENTAMAS]

So I checked my old archives and decided to share some notes with community about successful synthesis similar to original method, but with paraformaldehyde instead of 37% formalin.
Just to confirm it's valid and one of the most accessible route to pretty large amount of pure methylamine for amateur chemist.
My proportions was a bit different:
Paraformaldehyde : NH3*HCl : dH2O as 1 : 1.3 : 1.4
A little bit more ammonium to formaldehyde ratio is because I'm not limited in NH3 hydrochloride and for my next syntheses small amount of it doesn't bother as much as dimethylamine, so I decided shift a bit equilibrium to less alkylated products. But later I noticed that if make more distillation-crystallization cycles as I already described above, separation is pretty sharp, and after hot ethanolic extractions there is left negligible portion of NH3*HCl anyway.
Paraform. to distilled water ration is 1 to 1.4 just to get approx. 40% solution of formaldehyde, assuming that most commercial sources provide 95+-1% powder, the rest being water.
I didn't tested even more concentrated solutions, but assume it's still possible up to some level, with a bit more pronounced exothermic reaction.
If you start heat it, then at some point paraformaldehyde is fully depolymerized and clear solution is obtained, didn't remember exact numbers but likely near 80-90C, exoterm is very gentle in that case (for a batch in 5-6L flask and slow heating) and then RM can hold at that temperatures for some time by itself already without external heating. If you bring to that T fast or add some methanol to reduce boiling temp and induce bubbling for self-stirring of RM, then maybe at some point you will get over 100C and get the need to manually cool down a bit.

Very short version of synthesis looks like this:

1. Mix paraformaldehyde, ammonium chloride and dist. water and start gentle heat on oil bath or whatever you have.
2. Try to hold near but below 100C for at lest 6h, or 24h totally at 80-90C.
3. Cool down, filter solids by suction (don't wash with anything), transfer mother liquor to RBF and distill 10-15% of its volume under vacuum, control T that it not exceed 100C as before. Repeat 5-6 times
4. Take crude MeNH2*HCl crops (check visually, but in most cases 3th to 5-6th crop) and wash with Chloroform or DCM (need a bit more) to wash out traces of dimethylamine. If you have limited amount of these reagents you can just wash last crop or even skip this step.
5. Multiply hot extractions with abs. ethanol or methanol and crystallizations by cooling to achieve best possible purity. Also optional
6. Vacuum drying to remove traces of alcohol. Optional.

Beauty of this synthesis is that you can go to really large scale with it. Even make long-time (some days) big batch in 200L plastic HDPE can at reduced T, then transfer RM sequentially to smaller RBF and proceed as above when you have free time. At room temperature there is no appreciable biuld-up of by-products for months at least.

Pictures:

Spoiler: Paraformaldehyde with Ammonium chloride in 6L RBF

1.5 kg Paraformaldehyde + 1.95 kg Ammonium chloride in 6L round bottom flask.
At first I thought it's overfill but later everything goes into solution without much increase in volume.

Spoiler: Depolymerization occurred and clear solution obtained

Spoiler: Filtrate and first crops of wet crystalized ammonium chloride

Spoiler: Next crops and filtrate

Subsequent filtrates are slightly more colored.

Spoiler: Last ammonium chloride crop with a bit of methylammonium

Spoiler: Methylamine hydrochloride crops combined

Spoiler: [Optional] Chloroform wasings of still wet MeNH2*HCl

to get off last traces of Me2NH*HCl (dimethylamine)
clear water-white chloroform layer is below.

Spoiler: [Optional] Start of multiply hot ethanolic extractions of MeNH2*HCl

used self-made abs. EtOH
Heat to boiling, decant still hot, cool to crystalize MeNH2*HCl, filter, return the same spirit to boiling flask and repeat (add some more fresh EtOH if loses)
Repeat till there is left only NH3*HCl.
In my case there was negligible amount of it event at the begining,
but anyway crystallization is good for final purification from water, traces of dimethylamine and chloroform.

Final recrystallized and vacuum dried product:
(sorry I didn't save numbers of weight and yield, but that was pretty decent amount)