Methylation by means of formaldehyde

Methyl K-amyl carbinol, 7, 62 Methyl m-Amyl Ketone, 7, <5o, 62 i3-Methyl Anthroquinone, 4, 43 Methylation, 6, 64, 94, 96 Methylation by means of formaldehyde, 1, 75> 79 2, 17 3, 67 Methyl benzoate, 3, 71, 72 Methyl bromide, 3, 29 Methyl m-Butyl Ketone, 7, 62 Methyl mo-Butyl Ketone, 7, 62 Methyl scc-Butylmethyl Ketone,... 

Cularimine contains three methoxyls and is a secondary base since it yields an insoluble V-nitroso derivative and a neutral benzoyl derivative (m.p. 174°). In the course of a Hofmann degradation of it there was obtained cularine methine, and the final non-nitrogenous compound on oxidation yielded the acids obtained from cularine. It was also possible to convert cularimine into cularine by methylation by means of formaldehyde and formic acid, and therefore it has structure VIII. 

Werner, E,A. Methylation by Means oi Formaldehyde. Part I. The Mechanism of the Interaction of Formaldehyde and Ammonium Chloride The Preparation of Methylamine and of Dimethylamine Journal of the Chemical Society (1917) 111 844-853... 

This chapter compares the reaction of gas-phase methylation of phenol with methanol in basic and in acid catalysis, with the aim of investigating how the transformations occurring on methanol affect the catalytic performance and the reaction mechanism. It is proposed that with the basic catalyst, Mg/Fe/0, the tme alkylating agent is formaldehyde, obtained by dehydrogenation of methanol. Formaldehyde reacts with phenol to yield salicyl alcohol, which rapidly dehydrogenates to salicyladehyde. The latter was isolated in tests made by feeding directly a formalin/phenol aqueous solution. Salicylaldehyde then transforms to o-cresol, the main product of the basic-catalyzed methylation of phenol, likely by means of an intramolecular H-transfer with formaldehyde. With an acid catalyst, H-mordenite, the main products were anisole and cresols moreover, methanol was transformed to alkylaromatics. 

A compound that includes an aminopyrimidine ring as well as the quaternary salt present in thiamine shows preferential inhibition of absorption of that co-factor by coccidia parasites over uptake by vertebrates. The compound is thus used in poultry where coccidiosis is an economically important disease. Condensation of ethoxymethylenemalononitrile (42-1) with the amidine (42-2) leads to the aminopyrimidine (42-4), probably via the intermediate addition-elimination intermediate (42-3). The nitrile group is then reduced to the methylamino derivative (42-5) by means of hthium aluminum hydride. Exhaustive methylation, for example by reaction with formaldehyde and formic acid, followed by methyl iodide leads to the quaternary methiodide (42-6). The quaternary salt is then displaced by bromine, and the resulting benzyhc-like cylic halide (42-7) is displaced by 2-picoline (42-8). There is thus obtained amprolium (42-9) [43]. 

The synthesis of a triptan with a chiral side chain begins by reduction of the carboxylic acid in chiral 4-nitrophenylalanine (15-1). The two-step procedure involves conversion of the acid to its ester by the acid chloride by successive reaction with thionyl chloride and then methanol. Treatment of the ester with sodium borohy-dride then afford the alanilol (15-2). Reaction of this last intermediate with phosgene closes the ring to afford the oxazolidone (15-3) the nitro group is then reduced to the aniline (15-4). The newly obtained amine is then converted to the hydrazine (15-5). Reaction of this product with the acetal from 3-chloropropionaldehyde followed by treatment of the hydrazone with acid affords the indole (15-6). The terminal halogen on the side chain is then replaced by an amine by successive displacement by means of sodium azide followed by catalytic reduction of the azide. The newly formed amine is then methylated by reductive alkylation with formaldehyde in the presence of sodium cyanoborohydride to afford zolmitriptan (15-7) [15]. 

Treatment of the reduced intermediate (23-6) with butyl hthium leads to the anion from the removal of a proton on the methylene group reaction of that with methyl acetate affords the methyl ketone (24-1), which contains two of the three required side chain carbon atoms. The additional carbon atom and the basic function are incorporated by means of a Mannich condensation. Thus, reaction of (24-1) with A-methylpiperazine and formaldehyde leads to the aminoketone (24-2). The carbonyl group is then reduced with sodium borohydride and the resulting alcohol is dehydrated by reaction with phosphoms oxychloride in pyridine. In this case, too, the Z isomer is responsible for most of the activity. This is isolated from the resulting mixture of olefins to afford thiothixene (24-3) [25]. 

Methyl alcohol may be detected and estimated by conversion to methylaniline by means of iodine, phosphorus and aniline, followed by oxidation by stannic chloride to methyl violet. Other methods depend upon the conversion of the methyl alcohol to formaldehyde, which gives various colour reactions, with morphine sulphate and with fuchsine bisulphite. 

Biological systems overcome the inherent unreactive character of 02 by means of metalloproteins (enzymes) that activate dioxygen for selective reaction with organic substrates. For example, the cytochrome P-450 proteins (thiolated protoporphyrin IX catalytic centers) facilitate the epoxidation of olefins, the demethylization of N-methyl amines (via formation of formaldehyde), the oxidative cleavage of a-diols to aldehydes and ketones, and the monooxygenation of aliphatic and aromatic hydrocarbons (RH).3... 

A single plant operating in Texas, based on the noncatalytic controlled oxidation of propane-butane hydrocarbons, is reported to consume over 50 million gal annually of these light hydrocarbons together with large volumes of natural gas in the production of over 300 million lb of chemicals per year. Chemical products include formaldehyde purified to resin grade by means of ion-exchaiige resins, acetic acid, methanol, propanol, isobutanol, butanol, acetaldehyde, acetone, methyl ethyl ketone, mixtures of C4-C7 ketones, mixtures of C4-C7 alcohols, and propylene and butylene oxides. Catalytic liquid-phase oxidation of propane and butane is much more specific, and major yields of acetic acid are obtained. 

This reaction was initially reported by Eschweiler in 1905, and subsequently by Clarke and co-workers in 1933. It is the preparation of tertiary methylamines from primary or secondary amines by means of the treatment of those amines with an excess amount of aqueous formaldehyde and formic acid. Therefore, it is generally known as the Eschweiler-Clarke methylation. In addition, this reaction is also referred to as the Eschweiler-Clarke condition," Eschweiler-Clarke A -methylation, Eschweiler-Clarke procedure, -) Eschweiler-Clarke reaction, s.3j,7 Eschweiler-Clarke reductive methylation, Eschweiler-Clarke reductive -methylation, Clarke-Eschweiler methylation, Clarke-Eschweiler reaction,or Clarke-Eschweiler procedure. In this reaction, the formate anion donates its proton to reduce the imine or iminium salt, so that carbon dioxide is evolved. Thus the whole process is a reductive amination of formaldehyde. This reaction is very useful for the reductive amination, without the application of hydrogen gas, catalyst (e.g., Pd/C), and high-pressure apparatus and has been widely applied to alkaloid chemistry. A special case of such reductive amination that occurs on phenylethylamine and results in the formation of tetrahydroisoquinolines is also referred to as the Clarke-Eschweiler cyclization. In a few cases, the methylation also occurs on an aromatic ring during the reductive amination. J... 

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