Methylamine, reaction with ketones

A -Chloromethylamine attacks ketones in alkaline solution with formation of oxaziranes with cyclohexanone, compound 17 is produced in 50% yield. The reaction with aldehydes with zV-chloromethyl-amine yields predominantly acid amides. However, oxaziranes are also produced here as by-products. From benzaldehyde and A -chloro-methylamine, 2-raethyl-3-phenyloxazirane (15) was obtained in 10% yield. 

The bioreduction of carbonyl compounds with reductases has been exploited for many years, especially in the case of ketones, with baker s yeast Saccharomyces cerevisiae) being the most popular biocatalyst [45]. For instance, yeast treatment of 3-chloropropiophenone affords the expected (lS)-3-chloro-l-phenylpropan-l-ol, which was treated with trifluorocresol in tertrahydrofuran in the presence of tri-phenylphosphine and diethyl azodicarboxylate at room temperature to give (3R)-l-chloro-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propane and the later reaction with methylamine leads to (R)-fluoxetine that is an important serotonin uptake inhibitor (Scheme 10.19) [46]. 

Solid lactones or cyclic carbonates form linear hydroxy amides upon reaction with gaseous ammonia, methylamine, or ethylamine. For example, the compounds 277a-c and (ketonized) 279a-c are quantitatively formed at 0 °C and room temperature, respectively, without melting [12] (Scheme 39). 

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. 

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) facihtate the epoxidation of alkenes, the demethylation of Al-methylamines (via formation of formaldehyde), the oxidative cleavage of a-diols to aldehydes and ketones, and the monooxygenation of aliphatic and aromatic hydrocarbons (RH) (equation 104). The methane monooxygenase proteins (MMO, dinuclear nonheme iron centers) catalyze similar oxygenation of saturated hydrocarbons (equation 105). ... 

HYDROXYETHYL)METHYLAMINE (109-83-1) Combustible liquid (flash point 165°F/74°C oc). A strong organic base. Violent reaction with acids, strong oxidizers. Incompatible with organic anhydrides, acrylates, alcohols, aldehydes, alkylene oxides, substituted allyls, cellulose nitrate, cresols, caprolactam solution, epichlorohydrin, ethylene dichloride, glycols, isocyanates, ketones, maleic anhydride, nitrates, phenols, vinyl acetate. Increases the explosive sensitivity of nitromethane. Attacks aluminum, copper, zinc, and their alloys. 

The limited quantities of teloidine so far available have precluded an investigation of its structure. However, from the marked similarity of its chemical reactions with those of tropine and oscine and from the association of meteloidine with atropine and 1-scopolamine in Datura meteloides, teloidine was considered to be one of the stereoisomers of the trihydroxytropane, XCI. This has been confirmed by synthesis. Teloidinone, the Cj-ketone of teloidine, has been synthesized (3) (mesotartaric aldehyde, methylamine, and acetonedicarboxylic acid) under physiological conditions. Teloidine and an isomer were formed in the reduction of this ketone. 

This synthetic procedure, using the hydrochloride salt of the amine and sodium cyanoborohydride in methanol, seems to be quite general for ketone compounds related to 3,4-methylenedioxyphenylacetone. Not only were most of the MD-group of compounds discussed here made in this manner, but the use of phenylacetone (phenyl-2-propanone, P-2-P) itself appears to be equally effective. The reaction of butylamine hydrochloride in methanol, with phenyl-2-propanone and sodium cyanoborohydride at pH of 6, after distillation at 70-75 °C at 0.3 mm/Hg, produced N-butylamphetamine hydrochloride (23.4 g from 16.3 g P-2-P). And, in the same manner with ethylamine hydrochloride there was produced N-ethylamphetamine (22.4 g from 22.1 g P-2-P) and with methylamine hydrochloride there was produced N-methylamphetamine hydrochloride (24.6 g from 26.8 g P-2-P). The reaction with simple ammonia (as ammonium acetate) gives consistently poor yields in these reactions. 

Two reactions which should lend themselves to the synthesis of pyrrolidines with a wide variety of substituents have been published this year. In the first method Blake and co-workers have improved the versatility of a well known pyrrolidine synthesis from arylcyclopropyl ketones. By reaction with formamide in the presence of MgCl2, alkylcyclopropyl ketones (105) give good yields of pyrrolidines (106). The second method details the reaction of Schiff s bases of trimethylsilyl methylamine with acyl halides in the presence of alkenes and... 

Reactions Involving A-Bis(trimethyl ilyl)methyl Imine Derivatives. Bis(trimethylsilyl)methylamine condenses with aldehydes and ketones to form stable imines, which are useful intermediates in a variety of synthetic transformations. Thus, various A-bis(trimethylsilyl)methyl-l-aza-l,3-dienes underwent thermally mediated, frans-stereoselective C->N silyl migration to furnish l,2-bis(trimethylsilyl)-2,3-dihydropyrroles in good yields (eq 3). These products can be A-desilylated to afford 2-trimethyl-silyl-3,4-dihydropyrroles (68-93%), which can be reduced with lithium aluminum hydride to afford pyrrolidine derivatives. 

Formal isomerization of the double bond of testosterone to the 1-position and methylation at the 2-position provides yet another anabolic/androgenic agent. Mannich condensation of the fully saturated androstane derivative 93 with formaldehyde and di-methylamine gives aminoketone 94. A/B-trans steroids normally enolize preferentially toward the 2-position, explaining the regiospecificity of this reaction. Catalytic reduction at elevated temperature affords the 2a-methyl isomer 95. It is not at all unlikely that the reaction proceeds via the 2-methylene intermediate. The observed stereochemistry is no doubt attributable to the fact that the product represents the more stable equatorial isomer. The initial product would be expected to be the p-isomer but this would experience a severe 1,3-diaxial non-bonded interaction and epimerize via the enol. Bromination of the ketone proceeds largely at the tertiary carbon adjacent to the carbonyl (96). Dehydrohalogenation... 

A somewhat similar oxidation of terminal alkenes to methyl ketone and alcohol by 02 in the presence of Co(salMDPT) [salMDPT = bis(salicylideneiminopropyl)methylamine] and in ethanol solvent has recently been reported by Drago and coworkers (equation 244).560 Only terminal alkenes were found to be reactive with this catalytic system. The reaction is alcohol dependent and occurs in ethanol and methanol but not in t-butyl or isopropyl alcohols. The alcohol is concomitantly oxidized during the reaction, and may act as a coreducing agent and/or favor the formation of cobalt hydride. This oxidation might occur according to the mechanism of equation (243). 

The reaction of primary amines with aldehydes and ketones do not give the products expected from nucleophilic addition alone. This is because of the further reaction taking place once nucleophilic addition occurs, e.g. consider the reaction of acetaldehyde (ethanal) with a primary amine methylamine (Following fig.). The product contains the methylamine skeleton, but there is no alcohol group and there is a double bond between the carbon and the nitrogen. This product is known as imine or a Scbiffbase. 

Hexafluoroacetone imine has been prepared by the reaction of hexafluoroacetone with triphenyl phosphine imine,2 by the pyrolysis of N-phenyl-2,2-diaminohexafluoropropane,23 by the reaction of hexafluorothioacetone with hydrazoic acid,4 and by the reaction of ammonia and phosphorus oxychloride with hexafluoroacetone.4,5 The latter method, which is described here, is the most convenient for it does not require preparation of several intermediates or use of pressure equipment. This method has also been used to prepare the imines of other Huoroketones, including the imines of chloropentafluoroacetone, dichlorotetrafluoroacetone, and perfluorodiethyl ketone.5 Substitution of methylamine for ammonia in this procedure gives the N-methyl imine.5... 

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