This is the least desirable of all three processes [What do you mean by that? This is really easy to do! And the yield are fine!]. The yields are lower than the two rearrangements, and it requires substantial labor to get a decently pure product. Not "labor" as in difficult but "labor" as in a lot of it. I would suggest this only for those who have a large supply of Formaldehyde available to them (note - N. Coffey found formaldehyde at Home Depot - look for "Mildewcide" and dissolve it in enough water to make a 37% solution to depolymerize the paraformaldehyde).
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 -268 -
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 arid 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 HCI should be 100g.
Footnote 1 - The byproducts of the first step are Dimeth-oxymethane 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 most satisfactory method of drying products because of their hygroscopic nature. I suggest warming in an oven on a glass dish then transfering to a vacuum dessicator loaded with either concentrated Sulfuric Acid or Sodium Hydroxide in the bottom. It is not normally necessary to have absolutely dry Methylamine HCI anyway.
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) Wemer, J. Chem. Soc. 850 (1917) Sommelet, Compt. rend. 178, 217 (1924) Hofmann, Ann. 79, 16 (1851)
Urea is conveniently obtained as a constituent of many fertilizers and so it is easily obtained. Sources have indicated that a 501b 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:
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 SOC). 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 1 SOC in 20 minutes. The mixture should be refluxing in the condenser, and probably subliming in it as well unless heated "cooling" weter 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.
Synthesis of Acetamide from Ethyl Acetate and Ammonia
Ethyl Acetate is allowed to mix with concentrated Ammonia solution for several days to make Acetamide. This is a very attractive method because all the reagents involved are easy to acquire and cheap.
a) Preparation of Ethyl Acetate from Ethanol and glacial Acetic Acid
Dehydrate at least 100mL of grain alcohol to yield absolute Ethanol. 74mL (58g) will be required. Add this quantity of Ethanol to a round bottom flask with 225g glacial Acetic Acid and 3g of concentrated Sulfuric Acid. Heat at reflux on an electric heating mantle for 12 hours then attach a Vigreaux or Hempel fractionating column to distill off the crude ester at 76-77C. Change receiver flasks and recover the excess of Acetic Acid, bp 118C. Wash the first receiver contents with a half volume of saturated Sodium Bicarbonate solution then add 50g of anhydrous Sodium Sulfate (the salt of Sulfuric Acid and Sodium Hydroxide, dried in an oven at >100C for several hours) and distill the pure dry ester once again. Yield should be greater than 70g.
b) Reaction of Ethyl Acetate and Ammonia to make Acetamide
Add 44g of Ethyl Acetate and 90mL of concentrated Ammonia solution (-28%) to a 500mL round bottom flask with a stirrer magnet. Plug the neck with a thermometer in a thermometer adapter and stir gently for 48 hours or until the mixture becomes homogenous (stop the stirrer occasionally to check). Attach standard distillation apparatus but leave off the receiver flask at first, connecting a short piece of rubber tubing to the receiver adapter which is submerged in a beaker of dilute HCI (10-20%). Heat gently on a mantle to drive off the excess ammonia into the beaker. When no more bubbles come over then attach the receiver flask and commence distilling acetamide from 170C up, rapidly. Run 80C water though the condenser to prevent clogging. Once distillation slows to a crawl, remove the receiver flask and set aside in a hot water bath (80-90C). Clean up the glassware used for the distillation then use the receiver flask as the distilling flask and a glass container with screw-lid top as a receiver. Run 80C water through the condenser as before, and redistill the Acetamide,
which should come over completely at 216C using the heating mantle. Yield should be greater than 24g.
The lower nitroalkanes (sometimes refered to as nitroparaffins) are easily reduced by a multitude of systems, but by far the easiest, and also the highest yielding, is the Iron/Hydrochloric acid system. The reaction is:
HCI 4 RN02 + 9Fe + 4HzO---------> 4 RNHZ + 3 Fe304
First, your Nitromethane *may* require purification, especially if it was for "fuel" use. In this case, it needs to be vacuum distilled at a vacuum of better than 100mm Hg. At that pressure, it will come off at -47C. Distillation at atmospheric pressure is possible, but I do not recommend it due to the highly flammable nature of the compound and because it's flash point is 42C. It's your choice.
*CAUTION* - The lower nitroalkanes form shock and/or temperature sensitive EXPLOSIVE compounds with amines and hydroxides. BE CAREFUL, DAMN IT! You have been warned.
Heat the reaction mixture to 100C and hold for 14 hours. A temperature regulator is necessary if using a heating mantle, else use a large boiling water bath (if you will be doing it overnight, so it doesn't run out).
At the end of this time, allow to cool then add enough 25% Sodium Hydroxide solution to to get the pH above 11. Heat on a water bath or with gentle electric heat to drive the Methylamine off as a gas into the same beaker of Hydrochloric acid used as a trap during the reaction.
Evaporate the beaker contents to dryness on a glass plate in the oven to collect the crystals of Methylamine HCl (hygroscopic!). The yield should be approximately 15g (95%).
NOTE: Alternately, you may want to try using a Tin/HCI system which will give an equivalent yield in a much shorter time with the disadvantage that Tin is a much more expensive metal. The balanced equation for the reduction follows:
2CH3NO2 + 6Sn + 12H+ —> 2CH3NH2 + 3Sn(lV) + 4H20
Cognate procedure: Setup a flask with reflux condenser in which .25 mol of nitromethane, .38 mol of granulated tin metal and a stirrer magnet have been added. Carefully pour 115mL of 31.45% hydrochloric acid (muriatic acid) down the reflux condenser in 10-15mL increments, waiting for the reaction to settle down before pouring the next aliquot. If the reaction seems to get out of hand (excessive frothing, vapor escaping the reflux condenser, etc...) then quickly slide an ice bath in place until it slackens back down. Once all the HCI has been added, heat the mixture to reflux with an electric mantle for 1hr. At the end of this time, allow to cool, preferably in an ice bath, then add, carefully, a chilled solution of 75g sodium hydroxide in 125mL of water. If the flask contents start to bubble violently you will watch your yield go out the window, so add slowly! Since methylamine readily dissolves in water, you will need to distill the reaction contents carefully to first liberate the 40% constant boiling solution (bp: 53) and then the gas itself. The product is best captured by bubbling the distillation vapor into a beaker of hydrochloric acid (use a slight molar excess of HCI to insure no loss). Proceed as above by evaporating the bubbler solution to yield the crystals (take care when evaporating HCI solutions, as the excess acid will vaporize into the air, corroding ovens, lungs, etc...). [Vogel's, pg 892]
Additional notes - Nitromethane is found in high performance RC model fuel, usually as a mixture with methanol and various strange lubricants. One particular brand, found at a local hobby shop, was 55% nitromethane.
Johnson & Degering, J. Am. Chem. Soc., v61, 1939, pp3194-3195
Hexamine, more formally known as Hexamethylenetetramine, is easily and conveniently produced from Formaldehyde and Ammonia solutions. Formaldehyde may be easily produced by depolym-erizing, with heat, Paraformaldehyde (the only ingredient in OTC MildewCide). Hexamine is then reacted with Hydrochloric Acid and heated to yield Methylamine HCI in near quantitative yield.
The pertinent equations are thus:
6 HCOH + 4 NH3 -> 1 CsH12N4 + 6 H20 1 C6H12N4 + 4 HCl + 4 H20 --> 4 CH2NH3*HCI + 2 C02
a) Preparation of Formaldehyde
Place 3 3oz packets of Mildewcide into a 1L flask with an electric heating mantle and cork in the neck connected to a gas bubbler immersed in at least 550mL of distilled water. Heat the paraformaldehyde (what is in the Mildewcide) to between 180-200C (a temp, regulator is absolutely necessary for this step or use a silicone oil bath). The paraformaldehyde will depolymerize making formaldehyde gas in about 91% yield. Alternatively, the gas can be bubbled through the Ammonia solution directly (only for the brave!!!). If the Formaldehyde solution will not be used immedi
ately, 55mL of methanol should be added to it to prevent floccula-tion (repolymerization).
b) Preparation of Hex amine
*CAUTION* - Formaldehyde and ammonia solutions are extremely poisonous and quite noxious. Perform this step in a well-ventilated area (outside or with direct exhaust of the fumes)!
454mL of 40% Formaldehyde solution (Formalin) or 490mL of 37% technical grade solution is *slowly* poured into a tall beaker containing 250mL of 28% Ammonia solution. Stir vigorously the entire time. The solution will get hot as the reaction occurs, take care that the Formaldehyde solution is not added too rapidly otherwise it will boil over.
Allow this mixture to react, with stirring, overnight.
Evaporate off the water by heating the beaker in a hot water bath. (CAUTION: excess ammonia will be liberated!)
The yield of Hexamine should be 140g, white crystals.
c) Hydrolysis of Hexamine
140g of Hexamine is carefully dissolved in 400mL of Muriatic Acid (31.45% HCI) with vigorous stirring. After all is added, heat on the water bath. This will drive off the formed Carbon Dioxide and then the excess water. The yield of Methylamine HCI is 270g, colourless to just barely white deliquescent crystals.
If the crystals are opaque white and do not deliquesce quickly in air of average humidity (65% rh), they may be contaminated with some Hexamine. Washing 100g of the crude product with 100mL of Chloroform by stirring in a beaker then filtering, repeated as many times as necessary, will remove Hexamine. Methylamine HCI is insoluble in Chloroform whereas Hexamine is at the rate of 1g to 10mL.
Synthesis, March 1979, Blazevic, "Hexamethylenetetramine, A Versatile Reagent in Organic Synthesis", pp161-176"
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