Water/methylamine

Fig. Equilibrium acid-base reaction of methylamine with water. Methylamine can act as an acid when it is treated as a strong base like butyl lithium (Following fig.).

Problem 16.43. For each of the following pairs of compounds, indicate which compound has the higher value of the property. Explain, (a) Melting point hexylamine or dipropyl ether, (h) Solubility in water methylamine or octylamine. (c) Solubility in hexane methylamine or octylamine. id) Boiling point nonylamine or 1,8-octanediamine. 

Figure 4. SFC separation of five FMOC-amino acids 1, acetone (solvent) 2, valine 3, alanine 4, phenylalanine 5, lysine 6, serine. Conditions 15 cm x 4.6 mm ID packed column silica stationary phase CO2 mobile phase with methanol/ water/methylamine (98.99 1.00 0.01 v/v) modifier gradient indicated on chromatogram 42 °C UV detection at 269 nm. (reprinted with permission from Ref, 16).

Monomeihylamine, methylamine, CH3NH2-Colourless, inflammable gas with an ammo-niacal odour, very soluble in water, m.p. 

The solutions of all the methylamines in water are alkaline, but the alkalinity decreases with the number of methyl groups. 

Caution.—If the ethanol used to extract the methylamine hydrochloride is not absolute, i.e., if it contains traces of water, considerably less than the above suggested quantity will be required for the extraction, because the solubility of the hydrochloride will be markedly increased by the water present. The recrystallised material will now, however, contain traces of ammonium chloride. 

Dimethylaminomethylindole (gramine). Cool 42 5 ml. of aqueous methylamine solution (5 2N ca. 25 per cent, w/v) contained in an 100 ml. flask in an ice bath, add 30 g. of cold acetic acid, followed by 17 -2 g. of cold, 37 per cent, aqueous formaldehyde solution. Pour the solution on to 23 -4 g. of indole use 10 ml. of water to rinse out the flask. Allow the mixture to warm up to room temperature, with occasional shaking as the indole dissolves. Keep the solution at 30-40° overnight and then pour it, with vigorous stirring, into a solution of 40 g. of potassium hydroxide in 300 ml. of water crystals separate. Cool in an ice bath for 2 hours, collect the crystalline solid by suction flltration, wash with three 50 ml. portions of cold water, and dry to constant weight at 50°. The yield of gramine is 34 g. this is quite suitable for conversion into 3-indoleacetic acid. The pure compound may be obtained by recrystaUisation from acetone-hexane m.p. 133-134°. 

So now we have a modified method where one has ammonia, methylamine or ethylamine freebase saturated in a small amount of DMF. The author next suggested that a power pulse protocol would not necessarily be needed, but that the power output from the microwave should be between 20-40% of full power. Also, the water in the clay would still be needed for the reaction. 

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 waiter 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. 

For the aqueous solution Place 16mL 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. 

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, -IQg. 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 poiiion of Chloroform ( 10mL). 

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. 

Many procedures have been studied for detoxification of aflatoxkis, including heat and treatment with ammonia, methylamine, or sodium hydroxide coupled with extraction from an acetone—hexane—water solvent system. Because ki detoxification it is important to free the toxki from cellular constituents to which it is bound, a stabifi2ation of protekis uskig a tanning compound such as acetaldehyde (qv) or glutaraldehyde may be a solution to the problem (98). 

A modification of the direct process has recentiy been reported usiag a ckculating reactor of the Buss Loop design (11). In addition to employing lower temperatures, this process is claimed to have lower steam and electricity utihty requirements than a more traditional reactor (12) for the direct carbonylation, although cooling water requirements are higher. The reaction can also be performed ia the presence of an amidine catalyst (13). Related processes have been reported that utilize a mixture of methylamines as the feed, but require transition-metal catalysts (14). 

Isoprene [78-79-5] (2-methyl-1,3-butadiene) is a colorless, volatile Hquid that is soluble in most hydrocarbons but is practically insoluble in water. Isoprene forms binary azeotropes with water, methanol, methylamine, acetonitrile, methyl formate, bromoethane, ethyl alcohol, methyl sulfide, acetone, propylene oxide, ethyl formate, isopropyl nitrate, methyla1 (dimethoxymethane), ethyl ether, and / -pentane. Ternary azeotropes form with water—acetone, water—acetonitrile, and methyl formate—ethyl bromide (8). Typical properties of isoprene are Hsted in Table 1. 

Other preparative routes iaclude hydrogenation of succinonitdle in the presence of methylamine and hydrogenation of solutions of maleic or succinic acid and methylamine (82,83). Properties are Hsted in Table 3. l-Meth5i-2-pyrrohdinone is completely miscible with water, lower alcohols, lower ketones, ether, ethyl acetate, chloroform, and benzene. It is moderately soluble in aUphatic hydrocarbons and dissolves many organic and inorganic compounds. 

Fractionally distd under vacuum, then fractionally crystd twice from its melt. Impurities include acetic acid, methyl amine and H2O. For detailed purification procedure, see Knecht and Kolthoff, Inorg Chem 1 195 1962. Although /9-methylacetamide is commercially available it is often extensively contaminated with acetic acid, methylamine, water and an unidentified impurity. The recommended procedure is to synthesise it in the laboratory by direct reaction. The gaseous amine is passed into hot glacial acetic acid, to give a partially aq soln of methylammonium acetate which is heated to ca 130° to expel water. Chemical methods of purificatn such as extractn by pet ether, treatment with H2SO4, K2CO3 or CaO can be used but are more laborious. 

Tests for purity include the Karl Fischer titration for water this can be applied directly. Acetic acid and methylamine can be detected polarographically. 

A colourless, odourless, neutral liquid at room temperature with a high dielectric constant. The amount of water present can be determined directly by Karl Fischer titration GLC and NMR have been used to detect unreacted propionic acid. Commercial material of high quality is available, probably from the condensation of anhydrous methylamine with 50% excess of propionic acid. Rapid heating to 120-140° with stirring favours the reaction by removing water either directly or as the ternary xylene azeotrope. The quality of the distillate improves during the distn. 

When trigonelline is heated in closed tubes with baryta water at 120°, it gives rise to methylamine, whilst similar treatment with hydrochloric acid at 260° furnishes methyl chloride and nicotinic acid (pyridine-3-carboxylic acid), indicating that it is the methylbetaine of nicotinic acid. 

Mannich has prepared arecaidine aldehyde (IV) by allowing a mixture of formaldehyde, acetaldehyde and methylamine hydrochloride to stand at 70° and pK 3. Some dialdehyde, MeN(CH2. CHa. CHO)2, is formed and this by loss of water produces arecaidine aldehyde. The latter is, converted into arecoline by the VVohl and Johnson process described above. 

Merck and Maeder have patented the manufacture of arecaidine by loss of water from l-methyl-4-hydroxypiperidine-3-carboxylic acid. A method of producing the latter has been describd by Mannich and Veit and has been developed by Ugriumov for the production of arecaidine and arecoline. With the same objective, Dankova, Sidorova and Preobrachenski use what is substantially McElvain s process,but start by converting ethylene oxide, via the chlorohydrin and the cyanohydrin, into -chloropropionic acid. The ethyl ester of this with methylamine in benzene at 140° furnishes methylbis(2-carbethoxyethyl) amine (I) which on refluxing with sodium or sodium Moamyloxide in xylene yields l-methyl-3-carbethoxy-4-piperidone (II). The latter is reduced by sodium amalgam in dilute hydrochloric acid at 0° to l-methyl-3-carbethoxy-4-hydroxypiperidine (III) which on dehydration, and hydrolysis, yields arecaidine (IV R = H), convertible by methylation into arecoline (IV R = CH3). 

The importance of tropinone as a possible starting-point for the production of the therapeutically valuable alkaloids atropine, hyoscyamine, cocaine, tropacocaine and the artificial tropeines (p. 73) led Robinson to consider the possibility of preparing this substance by a simple method. Starting with the idea that the formula for tropinone (XXX) may be regarded as made up of the formulae of the residues of succindialdehyde (XXVII), methylamine (XXV III) and acetone (XXIX), he found that a mixture of these substances in water, when allowed to stand for thirty minutes produced tropinone, which could be detected by means of its characteristic dipiperonylidene derivative (bright yellow needles, m.p. 214°). 

The intermediate products (I) and (II) lose water, forming hydrohydrastinine and oxyhydrastinine respectively. Alkaline permanganate converts oxyhydrastinine into hydrastinic acid (III), C HgOgN, needles, m.p. 164° this in turn is oxidised by dilute nitric acid to hydrastic acid methylimide (IV), CJ0H7O4N, m.p. 227-8°, which, when warmed with potassium hydroxide solution, furnishes methylamine and hydrastic acid (V). 

---