Methylamine reaction with benzaldehyde

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. 

Pyruvate decarboxylase (PDC, E.C. 4.1.1.1) accepts other substrates besides pyruvate, its natural reactant As early as 1921, Neubergand Hirsch described the reaction of yeast with benzaldehyde and pyruvate to phenylacetylcarbinol (2-keto-3-hydroxy-propylbenzene) (Neuberg, 1921) in a carboligase side reaction which yields ephedrine after reaction with methylamine and catalytic hydrogenation (Figure 7.37). 

Depending on the reaction conditions, two different imines of formula CgHgN might be formed by the reaction of benzaldehyde with methylamine. Explain, and give the structures of the two imines. 

A very ingenious direct synthesis of i-ephedrine, avoiding the laborious resolution of the racemic mixture, has been devised by Hildebrandt and Klavehn (271) and described by Kamlet (272). Neuberg and Hirsch (273) in 1921 demonstrated that when equal mols of acetaldehyde and benzaldehyde are added to a carbohydrate solution actively fermenting by yeast, levorotatory l-phenyl-2-ketopropanol-l, C H5-CH(OH)CO-CHi, is formed. This compound on reaction with methylamine and catalytic reduction yields 1-ephedrine directly. 

Lamaty and collaborators have carried out solvent-free synthesis of nitrones in a ball mill [43]. Equimolar amounts of various aldehydes and A -substituted-hydrox-ylamines were used in conjunction with sodium bicarbonate (Scheme 3.64). For stoichiometric reaction between benzaldehyde and AT-methylhydroxylamine hydrochloride, small amount of dichloromethane was used. This reaction proceeded as a one-step condensation to give the corresponding nitrones in nearly quantitative yields, without the need to exclude air and moisture, in a shorter reaction time than by classical methods, but with comparable yields, where excess of reagents under inert atmosphere are reacted at room temperature or under heating for 1 or 2days (selected results. Table 3.32). Furthermore, the F,Z-isomeric ratio of the products obtained in ball-milling conditions were identical to those already reported in literature all the nitrones were in the more stable Z-form, with the exception of A -(naphth-2-ylmethylidene) methylamine A -oxide, known to be in the F-form. Microwave-assisted reactions gave lower yields than ball mill. 

Scheme 38.2 Synthesis of ephedrine by fermentation reaction on benzaldehyde, followed by reductive condensation with methylamine...

Raja and Perumal reported the synthesis of novel 2,6-diaryl-3-(arylthio)piperidin-4-ones via a four-component reaction consisting of arylthioacetones, 2-substituted aromatic aldehydes and methylamine or ammonium acetate <06CPB795>. Further elaboration of this four component reaction to a novel five component tandem Mannich-enamine-substitution sequence involving the reaction of ethyl 2-[(2-oxopropyl)sulfanyl]acetate, two equivalents of a substituted aromatic aldehyde, and two equivalents of ammonium acetate is shown below <06T4892>. When this five-component tandem reaction involves para-substituted benzaldehydes, the cis (193) and trans (194) diastereomers of thiazones are obtained. Alternatively, orf/zo-substituted benzaldehydes form only the trans (194) diastereomer along with an air-oxidized product 195. 

Normal nucleophilic substitution reactions of alkyl and aryl chloropyrazines have been examined as follows 2-chloro-3-methyl- and 3-chloro-2,5-dimethyl(and diethyl)pyrazine with ammonia and various amines (535, 679, 680) 2-chloro-3(and 6)-methylpyrazine with methylamine and dimethylamine (681, 844), piperidine and other amines (681, 921) 2-chloro-5(and 6)-methylpyrazine with aqueous ammonia (362) alkyl (and phenyl) chloropyrazines with ammonium hydroxide at 200° (887) 2-chloro-3-methylpyrazine with aniline and substituted anilines (929), and piperazine at 140° (759) 2-chloro-3-methyl(and ethyl)pyrazine with piperidine (aqueous potassium hydroxide at reflux) (930,931) [cf. the formation of the 2,6-isomer( ) (932)] 2-chloro-3,6-dimethylpyrazine with benzylamine at 184-250° (benzaldehyde and 2-amino-3,6-dimethylpyrazine were also produced) (921) 2-chloro-3,5,6-trimethylpyrazine with aqueous ammonia and copper powder at 140-150° (933) and with dimethylamine at 180° for 3 days (934,935) 2-chloro-6-trifluoromethylpyrazine with piperazine in acetonitrile at reflux (759) 2-chloro-3-phenylpyrazine with aqueous ammonia at 200° (535) 2-chloro-5-phenylpyrazine with liquid ammonia in an autoclave at 170° (377) 2-chloro-5-phenylpyrazine with piperazine in refluxing butanol (759) but the 6-isomer in acetonitrile (759) 5-chloro-2,3-diphenylpyrazine and piperidine at reflux (741) and 5-chloro-23-diphenylpyrazine with 2-hydroxyethylamine in a sealed tube at 125° for 40 hours (834). 

---