================================================================= This file is a part of the 1999 Hyperreal Drug Archives Snapshot. This snapshot is hosted by Erowid and will not be updated after October 1999. The information in these files may be out of date. See Erowid's Psychoactive Vaults for more current info. ================================================================= Newsgroups: alt.drugs.chemistry From: eleusis@netcom.com (Eleusis) Subject: The Methylamine FAQ v2.0 - Final! Message-ID: <3skaea$cf4_005@netcom.com> Date: Sun, 25 Jun 1995 18:38:02 GMT After I made my Request for Comments, I received a couple of excellent ones. Everything basically checks out, and the chemistry is solid, so have at it and let me know any successes and failures out there (anonymous, though, I don't want to know too much about you ). The Methylamine Data Sheet v1.0 (non-beta) --------------------------------------------------------------------- Table of Contents ----------------- 1) Introduction 2) Methylamine via Hoffman (Hypohalite version) 3) Methylamine HCl via Formaldehyde 4) Acetamide from Acetic Acid & Urea 5) Absolute Ethanol 1) Introduction --------------- Methylamine is one of the "trickier" chemicals to come by which is a necessary ingredient for all sorts of organic syntheses. For those of you too disinclined to find this information yourself , I have compiled a treatise on various methods of producing this compound from more "banal" chemical precursors. Some of the precursors are useful for other syntheses as well, so do what you like. Sources are provided for those of you who doubt my credibility (and you *should*, since you don't know me from the proverbial Adam). I have basically pirated them from the credited texts with modifications to verbiage and such to make it more 20th century and/or practical. Feel free to applaud or flame me: eleusis@netcom.com and be sure to get my check out my other various and sundry FAQs on Hydrobromic Acid, Sassafras Oil (new release) and more to come. * * * 2) Synthesis of Methylamine/Methylamine HCl via Hoffman Reaction ---------------------------------------------------------------- This Hoffman reaction takes an Amide and treats it with a Hypobromite or Hypochlorite solution to produce an Amine of similar composition to the original Amide but minus one Carbonyl (CO) group. In this case, Acetamide is the primary Amide, which is of formula CH3CONH2. We merely strip the CO off without damaging the structure too much and voilla, we get Methylamine, a volatile nasty gas of formula CH3NH2. See the similarities here. Alright, the unbalanced reaction is: CH3CONH2 + Ca(OCl)2 ----> (CH3CONCl)2Ca++ + H2O then (CH3CONCl)2Ca++ + NaOH ----> CH3NH2 + Na2CO3 We'll skip the theory normally present at this point, and merely interject that because we are introducing Methylamine into an aqueous solution, it will dissolve into the water rather than escape into the room to poison us all. This leads to the actual, hold your hand directions. Fantastic! One caveat. You can scale these reactions up or down within reason. What does that mean? I can't tell you, it depends. It is safe to say that doubling or halving will have no effect. Multiplying by ten times? Maybe. The key problems with scaling reactions like this have to do with heat gradients in the flask and inadequate stirring, such that secondary products form (like, say, dimethylamine or ammonium chloride). Use your best judgement. One reference to keep in mind (Thanks to J. Smith for sending this one) concerns the conversion of Acetamide to Chloracetamide via the addition of Calcium Hypochlorite and the time to get an effective yield. The original reference claims it only takes a few minutes whereas the reference below begs to differ. Either way, it can't hurt to let it sit for a long time, so you might as well. 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." Prepare an ice bath with water and Calcium Chloride to bring the temperature down to -15C or so. Setup glassware for simple distillation with magnetic stirring. Dissolve 82g of Calcium Hypochlorite in 250mL water in a beaker or flask. Swirl vigorously, though not all will dissolve. Place in the ice bath and add 50g of crushed ice. In a separate beaker/flask, dissolve 50g of Acetamide in 100mL water. Add 500g of crushed ice to this solution and swirl vigorously. Place a thermometer into the Acetamide soln. then add the Hypochlorite soln. slowly, in several small parts with gentle swirling. Make sure the temperature stays close to 0C because if it rises above 10C the solns. must be discarded. Allow the mixed soln. to remain in the ice bath for 15 minutes (or several hours...), gently swirling occasionally. All of the Acetamide will have converted to the methylisocyanate by this time. Now pour the mixture into the distilling flask (I like to put a long stem glass funnel into the top of the three-way adapter). Follow this with a solution of 120g NaOH in 200mL water at room temperature. Heating this mixture is the trickiest part of the synthesis. The thermometer should be positioned in the solution and the flask heated as rapidly as possible to 60C while being stirred magnetically (see Note 1 for my method on this). When it hits 60C, the rearrangement will commence with considerable heat evolved. Remove the heat while still stirring to allow the solution to react in the temperature range of 70C to 80C. If it appears it will head past 80C, quickly cool with ice or a cold water bath (See Note 1). The reaction completes within 15 minutes (the temperature will drop off). Before distilling this mixture, you need to choose between the aqueous or Hydrochloride form. In either case, heat to a gentle boil with stirring to liberate the methylamine as a gas. For the aq. soln.: String two air traps in tandem comprised of an Erlenmeyer flask with a two hole stopper and 175mL of chilled water. In one hole of the stopper, a glass tube should extend nearly to the bottom. Connect this tube to the condenser (I connect to the vacuum nipple on the receiver adapter, and use a receiver flask to catch any condensed liquid). The other hole connects to either the second trap or vents to the atmosphere (beware, if the soln. saturates in both traps, you will be exposing yourself to Methylamine, which is a highly unpleasant chemical in the least). The primary contaminant will be a slight amount of Ammonia. To purify... For the HCl salt: Do exactly as above except use 175mL each of 6N (normal) Hydrochloric Acid. The primary contaminant in this case is Ammonium Chloride (makes sense, eh). Mix the contents of the two traps and evaporate to dryness. Add 75ml of water and 48mL 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. Note 1 - A convenient way of alternating hot and cold water in a water bath, while still allowing magnetic stirring, requires two small bilge pumps, two buckets, a "Y" valve", a non-ferrous stainless steel water bath and some tubing. Mount a bilge pump in each bucket, one for hot water and one for cold. Connect the discharge side of both pumps to either "head" of the Y-valve, the tail connects to the inlet side of the water bath (the lower tube). The discharge side connects to the tail of another Y-valve, with each head going to each bucket. This allows you to quickly switch the water in the bath without hassle, just flick both valves at once. The magnetic stirrer should still be able to stir though the non-ferrous stainless steel bath (works for me). References: Journal of Chemical Education, v14, pg542 3) Synthesis of Methylamine HCl from Formaldehyde and Ammmonium Chloride ------------------------------------------------------------------------ Place 4kg of 37% Formaldehyde solution into a 5L RB flask along with 2kg of Ammonium Chloride. Rig the flask for simple distillation with a Claisen adapter, a thermometer long enough to extend 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 using a burner and hold the reactant temperature at 104C until, once again, nothing else comes over. This should take from 4 to 6 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) switled, and then an ice bath. Ammonium Chloride crystals will precipitate which the original text calls for centrifugation to remove. Personally, I would just filter with a chilled Buchner funnerl several times, cooling the solution down more each time. After this, concentrate the "mother liquor" (ie - the filtered reaction flask contents) under medium vacuum (water aspirator) and steam bath heat until the volume drops to approximately 2.5L. Repeat the above mentioned crystallisation/filtration process again to remove a second batch of Ammonium Chloride crystals. The total recovered Ammonium Chloride should be around 780 - 815g. We now move on to the extraction of the good stuff, Methylamine Hydrochloride, with the principal contaminants Ammonium Chloride (Still? Damn that stuff) and Dimethylamine Hydrochloride. Concentrate the reaction flask contents once again under medium vacuum on the steam bath until crystals form on the surface (at around 1.4 - 1.5L of volume). Cool the reaction flask rapidly, as above, and cold filter (for genuine draft taste) the crystals. Approximately 600 - 650g of crude product should be obtained, at which point you concentrate the mother liquor once more on the steam bath with reduced pressure to a volume of 1L and repeat to yield an additional 170 - 190g. Wash with 250mL of cold Chloroform then filter and "centrifuge" (if you are bothering). This removes most of the Dimethylamine HCl, leaving around 150g of Methylamine HCl and Ammonium Chloride. The original mother liquor is concentrated once again, on the steam bath, under reduced pressure (do I sound like a broken record yet?) until there is around 350mL left. Pour this out into a beaker which is situated in an ice bath and stir to prevent the formation of a solid cake. Centrifuge this paste (or, possibly, Buchner it) then wash the resulting crystals (170-190g) with 250mL cold Chloroform. Filter this solution then centrifuge to yield an additional 55-65g of Methylamine Hydrochloride. Your combined yield of crude product should be approximately 830-870g (620g + 180g + 60g) which contains as impurites water, Ammonium Chloride and Dimethylamine Hydrochloride. To purify this, you need to reflux with an alcohol for approximately 1/2 hour. Ideally, you should use n-Butyl Alcohol as the solubility of Ammonium Chloride in it is neglible. More practically, though, you will be using absolute Ethyl Alcohol (Ethanol with the water extracted - see how to do this later on in the FAQ). Place the crude product into a 5L RB flask, add 2L of Alcohol, fit an Allihn or Liebig condenser vertically and finally attach a Calcium Chloride filled drying tube to the top (a standard "dry" reflux setup). Reflux at boil for half an hour. Let the contents settle, then decant the liquid off, leaving undissolved junk in the bottom (the Ammonium Chloride). You should rapidly cool the supernatant, precipitating out Methylamine Hydrochloride. Recover the alcohol by filtering the crystals out on the Buchner, then repeat the whole process at least 4 more times. In the flask should remain approximately 150g of Ammonium Chloride, making it's total recovery 850-950g. Your yield of Methylamine Hydrochloride is 600-750g which is 41-51% of the theoretical. Footnote 1 - The byproducts of the first step are Dimethoxymethane and Sodium Formate. Footnote 2 - The Methylamine solutions in all steps should be cooled rapidly to promote smaller crystal formation. Footnote 3 - According to the original document, centrifuging is the only satisfactory method of drying products because of the deliquescent nature of them. As a suggestion, try placing the products into a vacuum dessicator to dry, instead. Footnote 4 - The solubility of Ammonium Chloride in absolute Ethanol is 0.6g/100g at 15C. The solubility in n-Butyl Alcohol is neglible, even at its boiling point. If you use n-Butyl Alcohol, you will only need to perform 3 reflux/filter operations to obtain sufficiently pure Methylamine Hydrochloride. References to this section: Sharp & Solomon, J. Chem. Soc. 1477 (1931) Werner, J. Chem. Soc. 850 (1917) Sommelet, Compt. rend. 178, 217 (1924) Hofmann, Ann. 79, 16 (1851) 4) Synthesis of Acetamide from Acetic Acid and Urea --------------------------------------------------- Urea is conveniently obtained as a constituent of many fertilizers and so it is easily obtained. Sources have indicated that a 50lb bag can be purchased for $15 in the US. It is of less than ideal purity from this source, so some washing will be in order (with what?). Glacial Acetic Acid is easily obtained from photographic supply stores in high purity and for cheap as well. This reaction produces Acetamide with such purity that the product does not even need to be recrystallized (the reaction goes to completion with no side products). The reaction is: CH3COOH + NH2CONH2 ----> CH3CONH2 + CO2 + 2NH3 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. Attach condenser, claisen adapter and place thermometer so that the bulb is around 1cm from the bottom, fully immersed. Heat on an oil bath 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. Push any deposited crystals back into the adapter as necessary. Continue refluxing until temperature can be raised to 195-200C (approximately 1.5 hours) Allow to cool, then rearrange the condenser for distilling (once again, in free air). Heat until the Acetamide just begins to reach the condenser (200C or greater) then it is most practical to have another condenser on hand to quickly replace the first. This is not so convenient with ground glass jointware, in which case it might be best to just stop distilling completely until cleaning out the condenser or switching it. Continue heating 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 and allow to stand. If your product is only faintly odorous and is colourless, then it is considered pure. Melting point is 80.5C. 5) Preparation of Absolute Ethanol from "Everclear" or Rectified Spirits ------------------------------------------------------------------------ Absolute, or 99.5% water-free, Ethanol is frequently necessary in many Organic operations. It is quite easy to prepare from the azeotrope with water such as "Everclear" brand grain alcohol, "moonshine" or "Rectified Spirits" (an old term for the same thing). Dehydrate 100g of fresh anhydrous Calcium Oxide in a vacuum dessicator for 24 hours (a bit redundant, I know). Setup glassware for simple refluxing with water-cooled condenser and a Calcium Chloride guard tube. Place 500mL of Ethanol into the flask, quickly add the Calcium Oxide and reflux gently on the water bath for 6 hours. Allow the reflux 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). - eleusis@netcom.com - The Methylamine FAQ v2.0 Final - 06/24/95 - +--------------------------------------------------------------------+ | eleusis@netcom.com | | _ _ | | /o\ Give me lava lamps or give me death... /o\ | | \_/ \_/ | | | | "In constant pursuit of the perfect 'Stoli, soda and lime'..." | +--------------------------------------------------------------------+