|Table of Contents|
|3||Making Methylamine via Hofmann Rearrangement (Hypohalite version)|
|4||Making Methylamine via Schmidt Rearrangement|
|5||Making Methylamine HCl via Formaldehyde|
|6||Making Acetamide from Acetic Acid & Urea|
|7||Making Acetamide from Ethyl Acetate & Ammonia|
|8||Making Absolute Ethanol|
This document deals with the preparation of Methylamine and Methylamine Hydrochloride from non-restricted precursors. Both of these compounds are currently extremely difficult to purchase legitimately or otherwise. This is the third major version of the FAQ, and in this version I am adding more physical data on the syntheses as well as a new reaction called the Schmidt Rearrangement which might be more attractive to some. Also, the astute observer will notice I changed the ratios of reactants in the Hofmann as well as scaling it down by 5 times. This is the result of empirical testing to better accomodate the person with small scale glassware (like myself).
Please note that I am not a chemist by trade, but I have taken great pains to insure the accuracy of all information, including empirical testing. While this means I am not an authoritative reference, it also means that a non-chemist can put this information to use.
What's New? v1.5: I have tested many variations on the Hofmann process in order to make it more efficient and easier. In my empirical testing, I have come up with several process improvements that make life with Hofmann so much easier and much more efficient to boot. For one thing, I have sucessfully performed it without having to use any ice in the reactants, reducing the volume of reactants by over 50% (and less volume is less one has to distill to get the good stuff). Yield hasn't suffered at all, and though slightly more time is required to perform the first step, distillation has been effectively doubled in speed (good for those of us with 500mL flasks and such to work with). Also, I added a new process that some may find more convenient called the Schmidt Reaction. It is very similar to the Hofmann, but please note that I haven't tested it nearly so much. Perhaps in a future "final touch" version I will put more empirical data into it.
What's New? v2.0: I must warn against selecting the Schmidt reaction to make the product, as my experiences it with it have been less than pleasant. Do try to use a fume hood of some sort if you wish to pursue this otherwise highly attractive method. Also, I have re-written the Formalin/Ammonium Chloride method with a more practical view in mind. This new write-up makes it much more worthy of consideration - live and learn, eh? In addition, I have added another preparation of Acetamide which uses all OTC (well, except for the Calcium Oxide) reagents and is both cheap and easy.
A1) Methylamine, or more correctly Monomethylamine, is of formula CH3NH2, a simple primary amine. It is a noxious, acrid gas which is quite nasty and a tad on the explosive side. For this reason, it is usually sold or prepared as it's hydrochloride salt, or as an aqueous solution of about 40% concentration. The HCl salt is in the form of white deliquescent crystals, and is frequently substitutable for the aq. soln. in many synthesis preparations.
Q2) What is this lovely compound used for?
A2) Methylamine/HCl has a number of uses in which it is impossible or highly impractical to substitute. Several examples are:
Methylamination of Hydroquinone to result in the ring structure p-methylaminophenol, the Sulfate of which is the photographic developing agent Metol.
Aqueous Methylamine (40%) is used to prepare animal hides for taxidermy, especially when it is vital to preserve the hair.
Synthesis of complex ring structures via the Mannich Condensation in conjunction with an aldehyde and a ketone.
And, of course, it is a necessary for the preparation of several drugs (both legal and otherwise).
Q3) Where can I get it?
A3) You can't unless you happen to be in an industry that uses it or are prepared to sign your privacy away to the DEA. That's why this FAQ exists; so you can make it yourself. Besides, if you can't make it with the data provided in here, you have no business messing with it anyway.
Q4) What are the legal implications of having it?
A4) Well, it is required by any chemical supply institution that they take down all sorts of data on anyone attempting to purchase a kilogram or more of either the aqueous solution or the salt, but it has been my experience that no place will sell it to an individual in any quantity. I even have a friend who owns his own photography business and he says he couldn't buy any as well. I could go off on a long pedantic spiel about how ridiculous this is, but why bother. Possession of Methylamine is not a felony, in any amount, though you may violate some hazardous waste and/or zoning rules above a certain quantity. It's not the kind of thing you want to store next to your bed, anyway. If you have it in conjunction with other compounds, such as P-2-P or MDP-2-P, then if for some reason the DEA came a'knockin', you could be prosecuted for Conspiracy to Manufacture Amphetamines, which could be damaging to your lifestyle and health (see Code of Federal Regulations 21 for more info).
Q5) Can I make it?
A5) Definitely. If you have half a clue and some reasonable grasp of chemistry fundamentals, you can make a good chunk of methylamine in an afternoon. I am covering three individual processes in this FAQ that I feel are relatively easy but, primarily, because they give good yields. The ones I cover are:
Finally, I would be remiss if I did not mention that there are several other processes for producing amines, though I have not treated them. Some other processes to consider among the hundreds are:
On to the syntheses...
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-halide 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-halide method is much easier to perform, processwise, 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 resulting 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!|
You can scale these reactions up or down within reason. What is reasonable? I can't say, but I have done batches from .01 to 1 mole with no difficulty. The key problems in scaling this reaction have to do with heat gradients in the flask and inadequate stirring. Use your own judgement, keeping in mind that this is not an industrial process.
One reference to keep in mind (Thanks to J.W. Smith for sending this one) concerns the first step of the reaction.
"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 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 0C or less as possible; 2) Keep the Hypochlorite solution as it is being added as close to 0C or less as possible; 3) After half the Hypochlorite solution has been added, place a plastic bag with 50-100g 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 8lb bag of ice ahead of time!|
Next you will prepare three solutions.
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 HCl) 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 Buchner 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 Buchner funnel with suction. The yield of Methylamine 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.
To make Methylamine or the HCl salt using the Schmidt Rearrangement, you start off with glacial Acetic Acid. You might be saying to yourself, "Damn, why bother with the Hofmann!" since glacial Acetic Acid is so easy to get, but, there is a drawback... And that is Hydrazoic Acid, which is not easy to get. As well, Hydrazoic Acid is extrememly poisonous and should not be handled without a fume hood under any circumstances. Really. This is coming from a guy who has no problem distilling Ether solutions in his kitchen, so take it seriously. Why bother, then? Well, because you can generate the Hydrazoic Acid in situ using Sodium Azide and conc. Sulfuric Acid. I have not personally tried this because I don't have a powder addition funnel. Anyway, Sodium Azide is not too hard to come by through chemical supply houses and Sulfuric Acid is easy to acquire in the form of Instant Power Drain Opener. This reaction must be performed in an area of adequate upward ventilation, or at least with the air flowing away from you.
|NOTE In the initial testing of any undesireable interaction between Sodium Azide, Acetic Acid and Sulfuric Acid, I mixed 5mL of each into a small cup underneath my "fume hood". Though I smelled nothing, within seconds my head felt like it was expanding, my heart started racing, and I felt more weak and confused than normal. I just barely escaped and recovered in 15 minutes, but, Needless to say, this procedure is a tad on the dangerous side. You have been warned.|
The intermediates in making amines are isocyanates (O==C==N) just like the Hofmann Rearrangement. The isocyanates are decomposed with water, just like the Hofmann. In fact, there is a lot of similarity between the Hofmann and the Schmidt reactions. Before I detail the synthesis steps, I should note that if you wish to generate the Hydrazoic Acid in the flask by adding Sodium Azide, you might need a powder addition funnel. This bit of equipment is quite pricey and it's likely you won't have one, so the first part of the synthesis details how to make the Hydrazoic Acid separately.
There are three variations on this process you may choose from:
|CAUTION This compound is EXTREMELY EXPLOSIVE and HIGHLY TOXIC! I am not exaggerating! Do not, under any circumstances, allow the acid to heat above room temperature (bp: 37C). Use latex gloves to handle, and dispose of small quantities using plenty of water followed by dilute baking soda/water.|
Place 49g of cold concentrated Sulfuric Acid into the addition funnel, but only after you make sure the stopcock is turned OFF. Ever so slowly add the acid to the flask, dropwise, such that the flask contents stay around 1C, and never go over 5C. This might take a while, be patient. After all is added, pour the flask contents into a separatory funnel (ventilation is absolutely required here) and separate out the aqueous layer. Your HN3 is dissolved in the Chloroform/Benzene layer. If you wish to determine the exact concentration of the acid, you may titrate it, but the reaction generally goes to completion with no secondary hydrazides forming as long as you kept the temperature where I told you to. Some HN3 might have gone to the aqueous layer, but mostly the resulting Sodium Sulfate will crowd it out. The resulting concentration, then, is the moles of Hydrazoic Acid over the the total moles of HN3 and your solvent (Chloroform = 117g/m, Benzene = 78g/m).
Setup your glassware for simple distillation with a claisen adapter, three way adapter, pressure-equalized addition funnel, water cooled condenser, vacuum adapter and receiver flask to catch any condensed solvent vapors.
Drop your stirrer magnet into the flask and add 250mL of Benzene or Chloroform (take your pick), Next, add .25 moles glacial Acetic Acid (15g) then .5 moles Hydrazoic Acid with stirring. Warm this solution to about 40C using a water bath. Make sure all joints are air tight. Add 20mL concentrated Sulfuric Acid very slowly. The reaction is mildly exothermic, so take care and watch the temperature. The reaction finishes within 2 hours. The amine is in the sulfate salt form. To convert to the hydrochloride salt form, first add an equinormal amount of 10% NaOH solution and stir well. Next, extract the free amine with ether and bubble HCl gas through it to precipitate out the crystals. Filter to recover.
Place 250g of Ammonium Chloride and 500g of technical Formaldehyde (37%, Formalin). Rig the flask for simple distillation such that a thermometer extends into the reaction mixture, and a Liebig or West condenser. Heat the mixture on the steam bath until no more distillate comes over, then turn up the heat and hold the reaction temperature at 104C until, once again, nothing else comes over. This should take from 4 to 5 hours. The distillate may contain interesting things, so check out footnote 1 for details on what to do with it. Next, the reaction flask should be cooled rapidly to room temperature by immersion into first a warm water bath (60C) swirled, and then an ice bath. Filter the solution on the vacuum Buchner funnel to recover ~62g of Ammonium Chloride crystals. Concentrate the filtrate using moderate vacuum and gentle heat until the volume is reduced to half. Filter the mother liquor once again after cooling quickly to yield a second batch of Ammonium Chloride, ~19g.
Transfer the filtrate to a ceramic evaporating dish and heat on a water bath until a crystalline scum forms on the top. Cool the dish quickly then filter the mess on the vacuum Buchner to yield ~96g of Methylamine Hydrochloride. Concentrate the filtrate once again to obtain a second crop of crystals, ~18g. Concentrate the filtrate a third time as far as possible using the water bath, then store the dish in a vacuum dessicator loaded with Sodium Hydroxide in the bottom for 24 hours. Add Chloroform to the residue left in the crucible to dissolve out Dimethylamine Hydrochloride (distill off the Chloroform to recover - good stuff) then filter on the venerable old vacuum Buchner funnel to yield an additional ~20g of Methylamine Hydrochloride, washing the crystals in the funnel with a small portion of Chloroform (~10mL).
Purification of the Methylamine HCl is in order now, so transfer all of the crude product to a 500mL flask and add either 250mL of absolute Ethanol (see end of FAQ for preparing this) or, ideally, n-Butyl Alcohol (see Footnote 4). Heat at reflux with a Calcium Chloride guard tube for 30 minutes. Allow the undissolved solids to settle (Ammonium Chloride) then decant the clear solution and cool quickly to precipitate out Methylamine HCl. Filter rapidly on the vacuum Buchner funnel and transfer crystals to a dessicator (see Footnote 3). Repeat the reflux-settle-cool-filter process four more times if using absolute Ethanol, or two more times if using n-Butyl Alcohol. The yield of Methylamine HCl should be 100g.
Place 125g Urea and 125g of Acetic Acid in a 500mL round bottom flask in preparation for simple refluxing with magnetic stirring and without cooling water (or use cooling water heated to about 80C). Attach condenser, claisen adapter and place thermometer so that the bulb is around 1cm from the bottom, fully immersed. Heat on the mantle gently to bring the temperature of the mixture to 150C in 20 minutes. The mixture should be refluxing in the condenser, and probably subliming in it as well unless heated "cooling" water is used. Push any crystals back down as necessary. Hold at reflux until the temperature rises to 195-200C (approximately 1.5 hours) Allow to cool, then rearrange the condenser for distilling (its really preferable to use 80C water in the condenser). Heat to collect nearly pure Acetamide starting at 200C with most coming over from 214-216C. If the product smells strongly of mice (as in the rodents), then recrystallization from warm methanol is in order. To recrystallize, take 50g of Acetamide, dissolve in 40mL warm Methanol, add 100mL Ether to crash it out and allow to stand. If no crystals have formed after an hour or so, gently scratch the inside of the beaker with a glass rod. If your product is only faintly odorous and is colourless to white, then it is considered pure. Melting point is 80.5C.
Dehydrate 75g of fresh anhydrous Calcium Oxide in a vacuum dessicator for 24 hours (a bit redundant, I know) or heat in an oven at 200C for 2 hours, then immediately transfer to the vacuum dessicator until use. Setup glassware for simple refluxing with a water-cooled condenser and a Calcium Chloride guard tube. Place 350mL of Ethanol into the flask, quickly add the Calcium Oxide and hold at gentle reflux on the water bath or heating mantle for 6 hours. Allow the mixture to stand overnight, then distill off the alcohol, discarding the first few mL (it may be more convenient to just vent the condenser to the atmosphere for the first couple of minutes after distillation has commenced). Yield should be better than 315mL. Store the absolute Ethanol in a tightly closed glass container as it will pick up water from the air rapidly.
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