Methylamine reaction with acetic acid

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. 

In a 2-1. flask provided with a mechanical stirrer, separatory funnel, and thermometer, are placed 189 g. (2 moles) of chloro-acetic acid and 150 cc. of water. The flask is cooled in ice water, and a cold solution of 160 g. (4 moles) of sodium hydroxide in 500 cc. of water is added, with stirring, at such a rate that the temperature does not exceed 30° (Note 1). AfLer all the alkali has been added, the cooling bath is removed, and an aqueous solution (Note 2) containing 31 g. (1 mole) of methylamine is added slowly. The reaction is exothermic, and the temperature is kept below 50° by occasional immersion of the flask in ice water. After all the methylamine has been added, the solution is allowed to stand for two hours to complete the reaction. 

It appears that treatment of phenacyl bromides 1239 with methylhydrazine in refluxing acetic acid leads also to 1,4-disubstituted triazoles 1244. Fivefold excess of methylhydrazine is used in these reactions. According to the proposed mechanism, structures 1240-1243, methylhydrazine has a double role, as a condensing agent and an oxidant. In the final account, three molecules of methylhydrazine have to be used to produce one molecule of triazole 1244, two molecules of methylamine and one molecule of ammonia. The basic triazole 1244 (X = Y = H) is separated in 59% yield. The reactions go well with electron-donating substituents (for X = OH, the yield is 81%), but electron-withdrawing substituents can lower the yield dramatically (11% for X = N02) (Scheme 206) <2003JCM96>. 

In 1972 Cava and Sprecker reported the formation of analogs of 149, in which one of the two sulfur atoms is replaced by oxygen or nitrogen (Scheme 9). Reactions of tetrabenzoylethane (146) with HCl or methylamine in acetic acid afforded 3,4-dibenzoyl-2,S-diphenylfuran (152) or 3,4-dibenzoyl-l-methyl-2,5-diphenyl pyrrole (153), respectively. 

A similar approach was taken for the synthesis of 45 by Miyaura. " Shaughnessy and Booth synthesized the water-soluble alkylphosphine 46, and found it to provide very active palladium catalysts for the reaction of aryl bromides or chlorides with boronic acids. The more sterically demanding ligand 47 was shown to promote the reactions of aryl chlorides with better results than 46. Najera and co-workers recently reported on the synthesis of di(2-pyridyl)-methylamine-palladium dichloride complexes 48a and 48b, and their use in the coupling of a variety of electrophiles (aryl bromides or chlorides, allyl chlorides, acetates or carbonates) with alkyl- or arylboronic acids very low catalyst loadings at Palladium-oxime catalysts 8a and 8b) have also been developed. In conjunction with... 

To 200 ml. of glacial acetic acid in a 1-1. round-bottomed flask is added slowly, with cooling in an ice bath, 151 ml. (54 g. of di-methylamine, 1.2 mole) of 40% aqueous dimethylamine solution, followed by 90 ml. (36 g. of formaldehyde, 1.2 mole) of 37% aqueous formaldehyde (formalin) solution. The flask is removed from the ice bath and equipped with a reflux condenser, through which 82 g. (90 ml., 1 mole) of 2-methylfuran (Note 1) is added all at once. Upon gentle swirling of the flask, an exothermic reaction may set in spontaneously if it does not, the flask is heated on a steam bath until reaction commences. In any event, the spontaneous reaction is allowed to proceed without further external heating. When it ceases, the reaction mixture is heated on a steam bath for another 20 minutes, cooled, and without delay poured into a cold solution of 250 g. of sodium hydroxide (Note 2) in 800 ml. of water. 

In the case of terpyridine and acridine derivatives, the bis(methylamines) are the most convenient intermediates. Substituted 4/-phenyl-2,2/ 6/,2"-terpyridines were prepared by reacting (ii)-propenons and iV-[2-(pyrid-2 -yl)-2-o octln l p ridinium iodide with ammonium acetate in acetic acid or in methanol. The terminal pyridine moieties were oxidized with 3-chloroperbenzoic acid to iV, A" -dio idcs followed by modified Reisserty-Henze reaction to obtain 6,6"-dicarbonitriles. The bis(methylamines) were obtained by reduction of the 6,6"-dicarbonitriles withborane (scheme 8 (Mukkala et al., 1993)). 

The first reported synthesis of MDMA was from safrole by converting it to its bromo derivative followed by reaction with meth-ylamine (Biniecki et al., 1960). Bailey et al. describe the synthesis of MDMA from 3,4-methylenedioxyphenylacetone using a Leuckart reaction with N-methylformamide and hydrolysis of the N-formyl derivative (Bailey et al., 1975). A third synthesis for MDMA described in the literature starts with peperonal which is reacted with nitroethane, ammonium acetate, and acetic acid to form a nitrostyrene derivative that is reduced to the ketone and then reacted with methylamine to form MDMA (Rabjohns, 1963). Using the method of Borch et al., MDMA can be synthesized by the reductive amination of the appropriate ketone in the presence of sodium cyanoborohydride (Borch et al., 1971). The MDMA syntheses used in clandestine laboratories are analogous. 

The incorporation of [2-14C]pyruvate and [l-14C]acetate into sugars 17 and 18 was investigated.27 Oxidation of the methyl glycosides of sugar 17 with periodate yielded acetaldehyde from the 1-hydroxyethyl branch. The acetaldehyde (2,4-dinitrophenyl)hydrazone was further oxidized by Kuhn-Roth oxidation to acetic acid, which was degraded by the Schmidt reaction to methylamine and carbon dioxide. Periodate oxidation of the methyl glycosides of sugar 18 produced acetic acid from the C-acetyl branch. The acetic acid was isolated, and purified as 1-acetamidonaphthalene. 

---