today I'm going to show you three ways to make the extremely important chemical methylamine methylamine is the simplest primary amine and as such its use in organic chemistry is pervasive for example methylamine is used extensively in the synthesis of accelerants propellants pharmaceutical insecticides fungicides and surfactants it's also used as a fuel additive a polymerization inhibitor a component and paint strippers a solvent a water treatment agent and a photographic developer however like some of the other most ubiquitous and commonplace lab chemicals you could imagine methylamine is regulated by the US government as a precursor chemical which makes it tough to purchase for reference here are just some of the other many commonplace lab chemicals scheduled as precursors this video took me months to actually release because I heard so often that this chemical was under particular scrutiny but in reality these chemicals are all identical in the eyes of the law and that said you'd have a hard time finding a video on my channel where I don't use at least one scheduled precursor so in the end I decided to just say screw it and make the list a little longer anyway the first method I'm going to show today is the reaction between pralid and ammonium chloride this route is by far the easiest but it's very messy timec consuming and requires a large amount of formalin which is not an easy chemical for many people to get to get started I went ahead and added 125 G of ammonium chloride and 250 ml of 37% formalin to a three neck round bottom boiler in flask I then connected a distillation head to one of the necks a thermometer to another and capped the third notice here that the thermometer is immersed in the solution as I want to monitor the temperature of the reaction mixture and not the vapor temperature I turned my heating mantle to Max and waited until the temperature at around 104° C now as the temperature increases a set of reactions begin to occur that eventually result in the formation of the chloride salt of methylamine which is much easier to collect in weigh than three Bas methylamine the first reaction that occurs is a direct condensation of faldy and ammonium chloride yielding water hydrogen chloride and the unsaturated compound methylamine this reaction happens spontaneously near ambient temperatures but as the temperature increases methylamine water and another molecule of faldy react to form methylamine and formic acid this is technically a redox reaction where in water is being oxidized by methylamine which itself is being reduced in the final reaction step the free base methylamine generated in the previous step will react with hydrogen chloride forming the target methylamine hydrochloride as for the reaction byproducts here the formic acid produced is for the most part oxidized to carbon dioxide and water as the reaction mixture heats up however formalin Solutions are stabilized with 10 to 15% methanol in order to prevent oxidation or polymerization of the formaly and some of the formic acid will react with this methanol forming meth formate and the acetyl methylol which both have very low boiling points and will distill off early in the reaction anyway once the temperature reaches 104° C I cut the heat and fiddled with it a bit until the temperature stabilized between 100 and 105° Celsius this temperature is held for about 3 hours while slowly distilling away water in the formic byproducts at a certain point the distillation slows to a virtual stop and can't continue without raising the temperature the issue though is that raising the temperature would favor the formation of undesired byproducts and as low as even 115° C the formation of dimethylamine is favored especially if excess form Malahide is present to fix this I go ahead and connect a vacuum to the distillation apparatus and vacuum distill away as much as I can until ammonium chloride begins to crash out of solution at this point I cut the heat completely allow my solution to cool the room temperature and then transfer it to an ice bath until it's cooled to 0° c i then passed the solution through vacuum filtration to collect the ammonium chloride which can be recrystallized and reused I then add my solution back to my boiling flask and continue heating at 105° C and repeat the previous step once the distillation had again slowed to a crawl at this point the reaction is virtually complete and most of the unreacted ammonium chloride has been removed to this end I go ahead and move my boiling flask back to the Heat and continue heating until the mixture had reached around 160° C in order to drive off as much water as as possible this is then poured into a beaker while still hot and I went ahead and rinsed the flask with some methanol to make sure all my crude methylamine made into the beaker this immediately began to harden as methylamine hydrochloride has a relatively high melting point and to begin purifying my Creed product I first needed to dissolve it in a minimal amount of hot methanol which took around 70 ml in my case now while methylamine hydrochloride is very soluble in hot methanol ammonium chloride isn't and virtually all the remaining ammonium chloride now be removed by passing this mixture through vacuum filtration the resulting solution is left overnight to crystallize and when I came back the next day some beautiful methylamine crystals had formed as a final step I put this Beaker into an ice bath for a few hours to crystallize out as much as possible and then pass the resulting solution through vacuum filtration to collect mostly pure methylamine hydrochloride these crystals are rinsed with a bit of ice cold methanol followed by some ice cold D chloromethane to remove any dimethylamine hydrochloride that might have formed and then vacuum desiccated for a few hours vacuum desiccation is extremely important here as methylamine hydrochloride is one of the most aggressively hygroscopic chemicals I've ever handled and will pull enough moisture out of the air to liquefy itself at 40% relative humidity in just a few hours anyway once my methylamine hydrochloride was allowed to dry completely I weighted giving me a final mass of 16. 9 6 G after this I was able to crystallize out another 10 G along with 30 G of ammonium chloride however ever this second batch was visibly lower Purity with a melting point of 195° c and not ideal if Purity is required to calculate percent yield I decided to use ammonium chloride consumed as my limiting reagent if I was left with 30 grams of ammonium chloride recrystallized the 95 grams were consumed and my percent yield would be 49. 9% out of the theoretical of 53.
9 7 G this yield would actually be considered quite good based on the literature I've read but given the quantity of starting reagents it still feels bad with that said I don't really love this method it requires valuable and very toxic formalin yields are pretty low and it's very messy smells horrendously of rotten fish and produces a lot of formate waste along with a lot of unreacted ammonium chloride which can obviously be reused but requires a recrystalization if you want to use it for anything else as a side note I did read on one Forum that this rea can produce yields in excess of 91% if vacuum reflux and distillation is used exclusively and the reaction temperature never allowed to exceed 90° C I found this out after I finished filming so I didn't try it out and I'm kind of skeptical of it but I might give it a shot in the future now the second method for making methylamine is basically analogous to the first but rather than building methylamine from ammonia and from alahh the methylamine produced here is formed by the decomposition of the more comp complex molecule hexamine to get started on method number two I added just under 70 G of hexamine fuel tablets to a beaker along with 170 mL of distilled water this solution was brought to a boil under constant stirring until the tablets had completely dissolved and then the solution was poured into a three neck round bottom boiling flask I then measured out 230 ml of 32% hydrochloric acid and poured it into an addition funnel which was connected to the center neck of the boiling flask the stop coock was open slightly to allow the hydrochloric acid to drip onto the hexamine solution dropwise under constant stirring until it was all added this was done because allegedly dissolving hexamine directly in hydrochloric acid would result in a much more aggressive reaction that almost exclusively forms ammonium chloride instead the desired reaction here is the hydrolysis of the hexamine B hydrochloric acid to form four molecules of ammonium chloride and six molecules of formaldahyde the resulting solution if this reaction proceeds favorably should be nearly identical to the solution used in the first synthesis and so once all the hydrochloric acid had been added all you have to do is set this up for a distillation and process it exactly the same as before this included another round of slow distillation at 104° C vacuum distillation to crash out excess ammonium chloride filtration to remove the salt repeat to remove more ammonium chloride heat to 160° C dissolve in methanol filter recryst crystallize filter again to collect the product and dry however while my footage here catches up to my lazy explanation I want to highlight a key difference in this reaction compared to the first method now if you'll remember I mentioned that the formalin solution used in the first method was stabilized with a significant quantity of methanol which produced methyl formate as a primary byproduct since there is no methanol here and the solution is far more acidic the primary byproduct will be formic acid not only that but the formation of formic acid here is favorable while in the first process the oxidation of formic acid to carbon dioxide was strongly favored as a result the distillate here contains a significant amount of surprisingly pure formic acid which I do collect in the end and will likely purify later on anyway once the reaction is complete and the resulting methylamine hydrochloride thoroughly processed and dried like before I went ahead and weighed the final product for a final mass of 25. 97 G of pure methylamine hyd chloride and another 9. 25 G of the impure stuff this time I was able to recrystallize 21 G of ammonium chloride and since 10 16.
84 G were generated by the hydrolysis of hexamine This Means 85. 8 G were used in the reaction giving me a theoretical yield of 48. 77 G this means my percent yield this time was 72.
2% although I might knock a few points off as I don't think I dried my methylamine is completely in this second run overall I definitely prefer this method to the first mostly because the reagents are way cheaper and easier to get for me I consistently get higher yields than I do with the first method for some reason and the byproduct formic acid is in of itself much more useful to me than methyl formate now the third and final method I have for making methylamine is by a Hoffman rearrangement of acetamide this route is by far the most interesting the fastest and the cleanest the only caveat here is that this method is more formally done using bromine and instead I used hypochloride as it's worked for me in the many past hofman rearrangements I've done on this channel however my yield ended up excessively low despite the reaction conditions being controlled very carefully and that said I believe that either my acetamide was too impure or bromine is required for this reaction to ever be truly efficient if there is sufficient interest I can retry this process using bromine and spend a bit more time verifying the purity of my acetamide but in the meantime here's how the hypochlorite route went I began by dissolving 45. 2 G of 73% calcium hypochloride bleaching powder representing 33 G of calcium hypochloride in a minimal volume of water this is then filtered to leave me with a reasonably clean solution of calcium hypochloride and then placed in the freezer to cool down to well below 0° c i then use a bit of heat to melt down some acetamide I made a few weeks ago by reacting acetic acid and Ura in order to transfer 20 G to a beaker which is then dissolved in around 40 mL of water and also placed in the freezer to cool down as much as possible after a few hours these are both removed from the freezer and placed on Ice I transfer about 105 G of this ice to a large Beaker and then put that on ice as well I then go ahead and salt the ice to make it colder by lowering its melting point and then I pour my acetamide solution into the ice spilled Beaker I then wait until the temperature reads well below 0° C at which point I begin to slowly add small splashes of my hypochlorite solution while stirring as much as I can making sure the temperature is well below 0° C before adding any more this reaction is highly exothermic and very heat sensitive that said if it heats up even above 10° C you need to scrap everything and start over in addition funnel might have actually been an even better idea here but for some reason I figured it wasn't worth the extra step in any case as the hypochloride is added you'll notice a lot of bubbling which I didn't really expect my assumption is that this was D chloramine that was produced when the hypochlorite reacted with ammonium acetate impurities in my acetamide this bubbling ceased after about a third of my hypochlor had been added and if this really is the result of acetamide impurity this accounts for at least a third of my loss alternatively there could have been such a high concentration of hydroxide ions in my hypochlorite that the reaction went to completion generating carbon dioxide but I'm not sure this is possible this fast and at such low temperatures anyway the way this should work is that when acetamide is treated with an alkaline source of bromine or chlorine they will react to form in bromo acetamide or in this case in chloroacetamide this is a two-step reaction where first the amine group is deprotonated by the hydroxide which then undergos an alpha substitution reaction with chlorine yielding the chloroacetamide once the reaction was complete I went ahead and poured my reaction mixture into a three neck round bottom boiling flask and quickly added my sodium hydroxide solution which resulted in even more bubbling in this step the additional hydroxide abstracts the remaining amide proton to give the chloro amide annion the chloro amide anion rearranges as the methyl group attached to the carbonal carbon migrates to the nitrogen at the same time the chloride ion leaves giving an isocyanate the isocyanate then reacts with water in a nucleophilic addition step to yield a carbamic acid which spontaneously loses carbon dioxide yielding the Amin product this reaction is also very exothermic but not enough to sustain itself starting from 0° C with that said to drive the reaction to completion I gently heat the mixture to around 60° C at which point it begins to Bubble at this point the reaction will be able to generate enough heat to sustain itself so I remove it from the Heat and allow it to rest during this time the reaction mixture Heats itself to the point that it climbs to nearly 70° cus and if it were to go beyond this temperature I would recommend placing the flask in an ice bath once the reaction mixture begins to cool the reaction is complete I then put the boiling flask back on the heating mantle and heat at 100° C this will cause methylamine to boil out of solution which is assisted by excess hydroxide in the solution the methylamine gas will then travel through this apparatus I've constructed and into cold water where it will readily dissolve into solution now a couple side notes while this happens I want to First clarify that the reason my reaction mixture turned white after the addition of the hydroxide was due to the formation of insoluble calcium hydroxide and if you were to use sodium hypochloride or bromine the reaction mixture would be a pale yellow second methylamine is aggressively soluble in its free based form much more so than even ammonia and that said ref flux is a genuine concern here which is the main purpose of the receiving flask I connected to the end of my short path apparatus if reflux were to happen it would simply reflux into the collection flask and not ruin the entire reaction third this methylamine gas can also be fed into hydrochloric acid to yield methylamine hydrochloride rather than the free base this reaction however is extremely aggressive and if you choose to go this route I would recommend suspending the funnel above the hydroc chloric acid rather than in it as I've done with the water here anyway getting back to my reaction here you can test if it's working by testing the pH of the receiving water with some litmus paper which should turn blue as methylamine is very alkaline this reaction is continued for about 30 minutes until I feel no more methylamine gases coming over and then I disconnect my apparatus before turning off my heat this step reminded me to reiterate that this should all be done under a fum Hood as I caught a whiff of the absolutely foul gaseous methylamine not only is methylamine one of the most terrible smelling chemicals out there it's also quite toxic along with most of the potential byproducts of this reaction anyway that's the entire process and in the end I'm left with a solution of free base methylamine of unknown Purity or strength to try and get an idea of how much methylamine I actually synthesized I needed to make this into the hydrochloride salt and then isolate it to this end I first neutralized my crude methylamine solution with hydr chloric acid and boiled it down until the remaining liquid was around 145° c i then dissolved the residue in a minimal amount of in hydrous methanol and passed it all through vacuum filtration this caught a significant amount of what I can only assume is ammonium chloride which is discarded the filtrate is then transferred to a beaker and allowed to cool so that methylamine hydrochloride can begin to crystallize out make sure to pay attention to the shape of the crystals during this step as methylamine crystals will form these trans Lucent feathery crystals while ammonium chloride will form smaller opaque white crystals honestly that's something you should look out for in the previous two methods as well this is actually the only footage I bothered trying to get of methylamine hydrochloride actually crystallizing and since many of you seem to enjoy watching these I'm just going to give this a few more seconds to play before I resume the [Music] procedure [Music] anyway once this is killed below freezing to allow the methylamine to fully crystallize I collected it by vacuum filtration and rinsed the crystals in a minimal amount of chloroform and ice cold methanol to remove any impurities I dried the lamine hydrochloride further under a full vacuum for a few hours and then Wade them to get a final mass of just under 3 G or roughly a 133% yield I was able to more than double this by desperately crystallizing out the rest of the much more impure methylamine from the filtrate but even this new 27.
