[144, 145]~No one should be buying this stuff because it is extremely watched and extremely easy to make. It's best to make this chemical in large batches. In the reaction flask of a simple distillation apparatus is placed 2000g of 40% formaldehyde and 1000g of ammonium chloride. The mixture is slowly heated to 104°C during which time all of the ammonium chloride will dissolve and the solution will be a bright, clear golden color. Lots of sparkly C02 bubbles will be evolved and as the solution approaches 100°C a steady run of distillate will commence. After 4-5 hours of maintaining the temperature at 104°C nothing more will distill over and the heating is stopped. If the solution is allowed to heat over 104-105°C then there will be product loss.
As the solution cools a big old mass of unreacted ammonium chloride will form. The chemist removes this by vacuum filtration and saves the crystals for reuse at another time. The golden colored filtrate is placed back in the flask and distilled (with vacuum now!) to reduce its volume by about a third. Temperature is not so much a problem now as the chemist will let the stuff distill over at whatever temperature is necessary. Sometimes the reducing solution is so concentrated that the remaining ammonium chloride crystals will form in the hot solution as the flask is being heated. No harm done. Either the second batch of crystals form on their own or the chemist, after removing a third of the liquid, allows the flask to cool which will readily bring out a second crop. This second crop of ammonium chloride crystals is separated, saved and the filtrate is once again returned to the reaction flask to be reduced in volume by distillation.
The chemist may have to do one, or possibly two more volume reductions before all of the excess ammonium chloride is removed (usually just one more). Now, what the chemist will be looking at after the last removal of ammonium chloride is a light yellow, slightly viscous solution that is about 1/3 the volume of the original filtrate. The chemist puts this to distill once more. What often happens next is that while the chemist goes off to watch TV the solution will distill off just a little bit of volume and poof! the hot solution will become an instant mass of methylamine hydrochloride. If this doesn't happen for the chemist then she will just reduce a little bit and chill. Either way, what the chemist is going to have is a nice mass of methylamine hydrochloride crystals that she separates by vacuum filtration.
The way the chemist knows that she has methylamine and not ammonium chloride is that she compares the look of the two types of crystals. Ammonium chloride crystals that come from this reaction are white, tiny and fuzzy. The methylamine hydrochloride crystals are longer, more crystalline in nature and are a lot more sparkly. The chemist leaves the methylamine crystals in the Buchner funnel of the vacuum filtration apparatus and returns the filtrate to the distillation set up so it can be reduced one last time to afford a second crop. The combined methylamine hydrochloride filter cake is washed with a little chloroform, scraped into a beaker of hot ethanol and chilled. The methylamine hydrochloride that recrystallizes in the cold ethanol is vacuum filtered to afford clean, happy product (yield=50%).
There is no way this section would be complete without Eleusis' classic "Methylamine FAQ". It was Strike's first-ever introduction to this person's work and it is still Strike's favorite:
"Synthesis of Methylamine/Methylamine HCI via Hofmann Rearrangement
There are two approaches to producing an amine from an amide using the Hofmann rearrangement reaction. One way is to react the primary amide with an alkaline-haiide solution (eg - Sodium Hydroxide and Bromine). The other method is to use an alkaline-hypohalite solution (eg - Sodium Hydroxide and Calcium Hypochlorite). The astute observer will notice that there is *no* chemical difference in the two processes. One produces the Hypohalite in situ, the other uses the Hypohalite itself. Substitution of various halogens/ halides/hypohalites/hydroxides is acceptable, but I feel I have picked the best combination of maximal yield and ease of availability. Feel free to prove me wrong;-). Also, at least one text specifies that Sodium Hypochlorite produces much higher yields than Sodium Hypobromite. This delicious vindication is expected since Chlorine is a more reactive halogen than Bromine. Now, we are going to use Calcium Hypochlorite, in the form of powdered pool shock, because concentrated Sodium Hypochlorite is a rare, unstable creature indeed. Our yield will not suffer in the slightest because of this.
The main example presented will be the alkaline-hypohalite method as it is the easiest to acquire the necessary chemicals. It is of interest to note that the alkaline-haiide method is much easier to perform, process- wise, in that it is more forgiving of sloppy technique.
The general theory behind the process is that the hypohalite will convert the amide to a haloamide. This then spontaneously changes to the isocyanate when heated and decomposes to the amine from the water present. In effect, all that happens is that a Carbonyl (CO) group is stripped off the starting amide to yield the corresponding amine. Yields pre- purification are around 80%, post-purification average around 65%. Certain uses of the result ing amine will not require purification, though, so it will be left up to you whether or not to perform those steps.
To make methylamine we start with Acetamide. The general, unbalanced reaction process is thus:
*CAUTION* Methylamine is a poisonous, noxious inflammable gas. It has a strong ammonia/rotting fish-like odor. It's not as bad as Chlorine gas, though, which can be produced if one is careless in the beginning!
One reference to keep in mind (Thanks to J. W. Smith for sending this one) concerns the first step of the reaction.
Whitmore and Thorpe, J. of the Amer. Chemical Society, Vol 63 April 1941, p1118
"It was necessary to allow several hours for the formation of the N-chloroamide before heating to degradation temperature. With this modification it was possible to prepare methylamine...consistently in 78% yield. "
In my experience, this is a *true* statement. Please remember to keep the reactants well iced, though. Now, to begin:
In a large mixing bowl which can contain a smaller stainless steel mixing bowl, prepare an ice bath with water and salt to bring the temperature down to -10C or so. Setup your glassware for simple distillation with magnetic stirring beforehand because certain steps need to be performed quickly. Use a vacuum adapter to connect to the receiver flask, and attach some rubber or polypropylene tubing to the vaccum nipple to connect to a bubbler setup (a funnel inverted in a beaker, or a plastic aquarium aerator tube). The distilling flask should be sitting in a stainless steel bowl with nothing in it (you will add pre-heated oil to the bowl).
*NOTE* In order to make this as painless as possible, please observe the following recommendations: 1) Keep the mixing bowl temperature as close to OC or less as possible; 2) Keep the Hypochlorite solution as it is being added as close to OC or less as possible; 3) After half the Hypochlorite solution has been added, place a plastic bag with 50-1 OOg ice/salt/water mix into the bowl to help keep temperatures low (use this instead of directly adding ice to the reactants, which adds a considerable volume of water making the process less volumetrically efficient); 4) Purchase an 81b bag of ice ahead of time!
10g of Acetamide in 20mL of distilled water. 16.4g of Calcium Hypochlorite (Pool shock) in 50mL of hot distilled water 24g of Sodium Hydroxide (Lye) in 40mL of cold distilled water
This last solution should be prepared slowly as it is quite exothermic. Set all three aside in a freezer. Now prepare the mixing apparatus which will be a stainless steel "mixing bowl" suspended in the ice/salt bath made earlier. We use a stainless steel bowl here so that heat transfer will be maximal, while preventing any corrosive interaction. A glass bowl will not be sufficient for larger scale preparations as it will not conduct heat fast enough to prevent the reactants from going over 10C (at which point the Haloamide will decompose and you'll have to start over). Take the Sodium Hydroxide solution out of the freezer once it is cool, but not cold.
After the bowl has been sitting in the ice bath for a few minutes, add the Acetamide solution. Stir well until the solution has cooled to -10C. Now, *slowly* add the Hypochlorite solution to the mixing bowl in bursts of no more than a couple mL while stirring vigorously. If you do this perfectly, there will be no fizzing or bubbling at all. This depends on how cold you keep the mixture, and how slowly you add the pool shock! Realistically, the considerable heat evolution of the reaction will make adding the last few mL a trying task! Keep an additional 50g of ice on hand to throw directly into the mixture if necessary. This solution *may* evolve Chlorine gas so you should obviously perform this step under a fume hood or outside). Keep stirring until it has calmed down and turned a turbid colorless to light green Let it sit for 2 hours, stirring occasionally and making sure that it never gets warmer than 5C.
After the 2 hours is up, add the Sodium Hydroxide solution quickly with stirring. The solution should immediately turn a chalky, milk white. That's because a lot of Sodium Carbonate just got generated. You no longer need be concerned over it's temperature, so you can leave the solution in this state overnight if perhaps the hours have passed by too quickly and you've suddenly realized it's 2:00am.
Preheat a water bath on the stove (or wherever) to about 80C and place the stainless steel mixing bowl in it. Once the temperature of the solution hits about 65C, take the bowl out and set aside while stirring all the while. This is where it rearranges, and the reaction is exothermic enough to sustain it's temperature nicely. If you find the temperature climbing past 80C, immerse the bowl into some cold water briefly. After about 15 minutes the temperature will start to fall, at which point you should transfer the whole mess to the distilling flask. Before you continue you need to choose whether you want to make the hydrochloride salt or the aqueous solution of Methylamine, though.
Heat the flask using an oil bath to 100C after adding this solution to effect gentle boiling which will drive off the Methylamine as a gas. In my experience, misbehavior is likely to occur at this point One particular problem to watch out for is the sucking back of bubbler solution (be it plain water or 6N HCI) into the receiver flask. I don't know why the pressure in the distilling flask would go below atmospheric, and therefore cause this to happen, but it has several times with me. Needless to say, this results in a serious mess and *botches* the whole process (I have found a cure for this by using an automotive one-way vacuum valve, like a PCV).
Continue heating the flask contents until you have collected around 100mL of distillate in the receiver.
For the aqueous solution: Place 18mL of cool distilled water into your bubbler setup. The *expected*, not theoretical, yield of Methylamine from this amount of reactants is 7 grams. I have used a plastic aquarium aerator tube as the bubbler with excellent results. Sure beats using an inverted funnel.
For the HCl salt: Do exactly as above except use 6N Hydrochloric Acid. 6N HCl may be produced by diluting 60.4mL of "Muriatic Acid" to 100mL with distilled water. Evaporate the bubbler solution to dryness then add 15ml of water, 10mL 10% NaOH soln. and heat gently to a boil with constant motion until dense white fumes appear. This will remove the Ammonium Chloride. Remove from heat while stirring as it cools down. Pulverize the dry residue, then reflux with absolute Ethanol for several minutes. Filter the refluxed soln. on a heated Büchner or Hirsch funnel, then distill the alcohol off the filtrate until crystals just begin to form. Allow the soln. to cool naturally to room temperature, then cool further in an ice bath. Filter the solution on a chilled Büchner funnel with suction. The yield of Meth^'amine Hydrochloride should be around 55% of the theoretical.
To clean the white residue off of your glassware, dump some muriatic acid straight from the jug onto them and swirl.
References: Journal of Chemical Education, v14, pg542 Organic Reactions volume 3 Vogels Elementary Practical Organic Chemistry, pg574
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