Methanol methylamines from

Ninety-eight grams of 6-chloro-2-chloromethyl-4-phenylquinazoline 3-oxide hydrochloride were introduced into 600 cc of ice cold 25% methanolic methylamine. The mixture was initially cooled to about 30°C and then stirred at room temperature. After 15 hours the reaction product which precipitated was filtered off. The mother liquor was concentrated in vacuo to dryness. The residue was dissolved in methylene chloride, washed with water and dried with sodium sulfate. The methylene chloride solution was concentrated in vacuo and the crystalline residue was boiled with a small amount of acetone to dissolve the more soluble impurities. The mixture was then cooled at 5°C for 10 hours and filtered. The crystalline product, 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide, was recrystallized from ethanol forming light yellow plates, MP 236° to 236.5°C. 

Bottini and Gal (81) added 2,6-cycloheptadienone (148), prepared from cycloheptanone in four steps (82), to a solution of methanolic methylamine and obtained tropinone (124) in 64% yield (Scheme 6). This reaction was suggested long ago by Robinson (66). 

Figure 7.15 Separations of opium alkaloids on bare silica. Column = x 0.46 cm ID stationary phase, 5-/im LiChrosorb Si-60 silica mobile phase, carbon dioxide-methanol-methylamine-water (83.37 16.2 0.15 0.23, w/w) Solutes 1, narcotine 2, papaverine 3, thebaine 4, codeine 5, crytopine 6, morphine. [Reprinted from Ref.20, J. Chromatogr. 437, 351 (1988) with kind permission of Elsevier Science Publishers, The Nether-, lands.]...

Silica Si02 Al203 Methylamine from methanol and hydrogen sulfide... 

A two-step synthesis of 1,4-disubstituted imidazoles (8) from TOSMIC (1) plus an aldehyde, followed by reaction with ammonia or a primary amine, proceeds via a 4-tosyloxazoline (11). The reaction sequence could be classified as 1,2 and 1,5 bond formation, 1,5 bond formation, or transformation of another heterocycle. There are, however, analogies to the aldimine reactions, and so the process is detailed at this stage. Certainly the synthesis is carried out in two steps often with isolation of the oxazoline (see also Chapter 6). Heating (11) with a saturated solution of methanolic ammonia gives a 4-substituted imidazole with methanolic methylamine a 1,4-disubstituted product is isolated as a single regioisomer (Scheme 4.2.4). Some of the oxazolines cannot be isolated as they are unstable oils which have to be heated immediately with the amino compound [12]. Related is the synthesis of 2-carbamoyl-4-(2 -deoxy- 0-D-ribofuranosyl)imidazole [13]. 

The production of methylamines from methanol and ammonia is economically affected by the ratio of the demands of the three products (monomethylamine, dimethylamine, and trimethylamine). The recycle of trimethylamine will reduce the production of dimethylamine and trimethylamine relative to the production of monomethylamine. Similarly, the dilution of the reaction mixture with water will result in a relative increase in the production of monomethylamine. A mixer-heat exchanger-mixer portion of a methylamine plant is a proposed capital investment which would allow the relative production of the methylamines to be varied to meet changes in demand. 

The production of methylamines from anhydrous ammonia and methanol is an established industrial process that consumes about 4% of the total U.S. metha-... 

UCB S.A. in Belgium has developed a continuous process for methylamines from ammonia and methanol, which is said to be pollution-free and for which the overall yield is 96.5 percent. ... 

Now, contrary to popular opinions, this method need not be conducted in a sealed pipe bomb. Secondary amination by substitution is as much a reaction of opportunity as it is of brute force and heat. In fact, heating can tend to cause the reformation of safrole and isosafrole. So the simplest way to do this would be to use 500mL of ammonium hydroxide or alcoholic ammonia or, for those wishing to make MDMA or meth, 40% aqueous methylamine or alcoholic methylamine (to tell you the truth, methylamine is preferable in this method because it is more reactive that ammonia so yield will increase). This 500mL is placed in a flask and into it is poured a solution of 35g bromosafrole (30g phenylisopropyl-bromide) mixed with 50mL methanol. The flask is stoppered and stirred at room temperature for anywhere from 3 to 7 days. The chemist could also reflux the same mixture for 6-12 hours or she could throw the whole mix into a sealed pipe bomb (see How to Make section) and cook it for 5 hours in a 120-130°C oil bath. 

Methylamines are produced from the vapor reaction of methanol with ammonia over a siUca—alumiaa catalyst. Methyl esters result from the reaction of methanol with the corresponding organic or inorganic acid as shown, eg, for methyl methacrylate. 

Doubt (75ZN(B)822) has been cast on a number of claims for the formation of 2-azetin-4-ones from cycloaddition of activated isocyanates to acetylenes (70TL119). The simple 2-azetin-4-one (246) was not isolated or even detected directly at -50 °C in the photofragmentation of compound (245), but indirect evidence for its formation was the isolation of adducts (248 X = MeO, MeNH) in the presence of methanol or methylamine (75TL1335). The most convincing evidence for an isolable 2-azetin-4-one involves treatment of the... 

Changing the atom bound to a methyl group from carbon to nitrogen to oxygen, as in going from ethane to methylamine to methanol, produces a decrease in the rotational barrier from 2.88 to 1.98 to 1.07kcal/mol. This closely approximates the 3 2 1 ratio of the number of H—H eclipsing interactions in these three molecules. 

Entries 11 and 13 in Table 3.4 present data relating the efiect of methyl substitution on methanol and methylamine. The data show an increased response to methyl substitution. While the propane barrier is 3.4 kcal/mol (compared to 2.88 in ethane), the dimethylamine barrier is 3.6kcal/mol (compared to 1.98 in methylamine) and in dimethyl ether it is 2.7 kcal/mol (compared to 1.07 in methanol). Thus, while methyl-hydrogen eclipsing raised the propane barrier by 0.5 kcal/mol, the increase for both dimethylamine and dimethyl ether is 1.6 kcal/mol. This increase in the barrier is attributed to greater van der Waals repulsions resulting from the shorter C—N and C—O bonds, relative to the C—C bond. 

The two major chemicals based on synthesis gas are ammonia and methanol. Each compound is a precursor for many other chemicals. From ammonia, urea, nitric acid, hydrazine, acrylonitrile, methylamines and many other minor chemicals are produced (see Figure 5-1). Each of these chemicals is also a precursor of more chemicals. 

Conversion of methanol into formaldehyde by methanol dehydrogenase. A complex array of genes is involved in this oxidation and the dehydrogenase contains pyrroloquinoline quinone (PQQ) as a cofactor (references in Ramamoorthi and Lidstrom 1995). Details of its function must, however, differ from that of methylamine dehydrogenase that also contains a quinoprotein—tryptophan tryptophylquinone (TTQ). 

To a mixture of 360 g 50% KOH and 138 ml methanol, add with stirring at -5° 70.5 g dimethyl ester of acetone dicarboxylic acid (dimethyl-beta-ketoglutarate — see method 3 for preparation) and let temperature rise to about 25° over V2 hour. Let stand ten minutes, cool to 0° and add 65 ml ether. Filter, wash precipitate with 65 ml ethanol and 150 ml ether at 0C to get 75 g (III). To 322 ml 1N HCI at 80c, add 41.1 g (I I) and stir twenty minutes cool to 10°, add 211 ml IN HCI, 98.2 g (Ml). 26.4 g Na acetate and 28.2 g methylamine HCI. Stir four hours at room temperature, cool to 10°, and saturate with 410 g KOH. Extract four times with methyl-Cl or benzene (75 ml each, fifteen minutes stirring) and evaporate in vacuum to get the methyl ester of tropan-3-one-2-COOH (IV), which precipitates from the oil (can distill 85/0,2). Test for activity. Dissolve 28.3 g (IV) in 170 ml 10% sulfuric acid cool to -5° and treat with 3.63 kg 1.5% Na-Hg amalgam with vigorous stirring at 0°. See below for easier methods of reducing (IV),... 

Similarly, ionized alcohols and ethers containing a chain of at least three contiguous carbon atoms attached at one end to the oxygen atom frequently expel water or the alcohol derived from the smaller alkyl group76-80. However, the corresponding ionized amines rarely eliminate ammonia or small alkylamines in great abundance. This contrast reflects energetic factors. Water and small alcohols are extremely stable molecules (AHf = —240 and —190 kJ mol-1, respectively, for water and methanol), but ammonia and methylamine are not particularly stable (AHf = —20 and —25 kJmol-1, respectively)82,83. Moreover,... 

Acetylgramine. This substance is active (IV. in mice) at doses of 5 mg per kg and less, making it quite potent. It potentiates response to DMPP (l,l-Dimethyl-4-phenylpiperazinium iodide) and blocks response to acetylcholine and adrenalin. Reflux a mixture of 15 g of 5-aeetylindole or analog (in equimolar amount), 7.55 g of 37% aqueous formaldehyde, 17 g of 25% aqueous di-methylamine, 25 ml of acetic acid, and 250 ml of methanol for 3 hours. Concentrate in vacuo to 20% of original volume, treat with 100 ml of water, wash with chloroform, chill in freezer, and make basic with 20% NaOH. Filter off the crystalline precipitate and wash with cold (near freezing) water to get a little over 17 g of the title product. Recrystallize from benzene to purify. It is unknown to me if this is active orally. 

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