Methylbenzylamines

H NMR spectra of (a) 4 methylbenzylamine and (b) 4 methylbenzyl alco hoi The singlet correspond mg to CH2N in (a) is more shielded than that of CH2O in (b)... 

Isobutylamine and 2 phenylethylamine can be prepared by the Gabriel synthesis ten butyl amine N methylbenzylamine and aniline cannot... 

Preparation of Amines. Amines are prepared by heating aUphatic, aromatic, or cycHc ketones with ammonium formate, formamide, or an A/-substituted ammonium formate at 165—190°C (Leuckart reaction). For example, cx-methylbenzylamine is prepared by the reaction of acetophenone with ammonium formate. 

Support for initial N alkylation is provided by the reaction of N-isobutenyl-N-methylbenzylamine (26) with methyl iodide, which gave a,a-dimethyb hydrocinnamaldehyde (27) on hydrolysis (ii). 

Addition of p-tert-butylthiophenol 178 to the racemic furanone 168 in dry toluene, and in the presence of quinidine as a chiral catalyst, provided (/ )-168 together with the Michael adduct 179. The enantiomeric excess of the recovered furanone (R)-168 was determined via the addition of (/)-Q -methylbenzylamine This amine addition showed complete diastereofacial control to give the adduct 180 in quantitative yield (Scheme 50) (94T4775). 

The synthesis starts by condensation of readily available optically active (R)-(+)-alpha-methylbenzylamine with 4-phenyl-2-butanone to form an imine which is itself reduced by hy-drogenolysis (Raney nickel) to give a 9 1 mixture of the (R,R)-amine and the (R,S)-amine (4). 

One problem with reductive amination as a method of amine synthesis is that by-products are sometimes obtained. For example, reductive amination of benzaldehyde with methylamine leads to a mixture of iV-methylbenzylamine and i -methyldibenzylarnine. How do you suppose the tertiary amine byproduct is formed Propose a mechanism. 

To a solution of l. 47 g (0.03 mol) of sodium cyanide and 4.73 g (0.03 mol) of (-)-(.S)-x-methylbenzylamine hydrochloride in 5 mL of cold water is added 1 g (8.3 mmol) of free ( - )-(.S )-a-mcthylbcnzylaininc in 200 mL of CHjOH. 1.32 g (0.03 mol) of acetaldehyde is added at 0°C and the clear solution is kept at r.t. for five days. After evaporation of the solvent in vacuo, the residue is dissolved in 50 mL of 1 N HC1 and the solution is extracted twice with diethyl ether. After addition of 12 N HCl to adjust the acid concentration to approximately 5 N, the solution is retluxed for 6 h. The HCl is evaporated in vacuo and the residue is dried over sodium hydroxide. The crude. V-x-methylbenzylalaninc hydrochloride is dissolved in 200 mL of 50% ethanol and the pH is adjusted to 6.0 with NaHCOj. To this solution, 3.5 g of palladium hydroxide is added. After hydrogenolysis for 10 h, the catalyst is filtered off and washed with hot water. The filtrate is concentrated to 30%, and the pH is adjusted to 1 with dilute IIC1. The solution is evaporated to dryness and the alanine hydrochloride is extracted with three 20-inL portions of absolute ethanol. After cooling overnight at — 50°C, the precipitated salt is filtered. Pyridine is added to the alcoholic solution to precipitate crude alanine, which is dissolved in 2.5 mL of water. The pH is adjusted with pyridine to 5.5-6.0, and 10 mL of absolute ethanol arc added yield 0.45 g (17% over four steps) mp 290 C [a] 7 + 13.13 (0 = 2.32. 6 N IICi). 

The reaction of the imines, formed from 2-methylpropanal and (S )-a-methylbenzylamine with tert-butyl isocyanidc and benzoic acid under widely varied conditions, delivers the valine derivatives with only moderate diastcrcoselectivity (ratio of diastereomers less than 4 l)67. 

Figure 5.8 Deracemization of a-methylbenzylamine by using a variant monoamine oxidase in combination with NH3 BH3.

A reaction that involves dehydrogenation to an imine, which then reacts further is the reaction of primary or secondary amines with palladium black. The imine initially formed by the dehydrogenation reacts with another molecule of the same or a different amine to give an aminal, which loses NH3 or RNH2 to give a secondary or tertiary amine. An example is the reaction between V-methylbenzylamine and... 

As 29 had been recognized as the most accessible starting-material for the synthesis of racemic carba-sugars, its resolution was successfully achieved with optically active a-methylbenzylamine as chiral reagent. Reaction of 29 with (-l-)-a-methylbenzylamine gave a mixture of two diastereoisomeric salts [(+)-amine, (—)-29 and (+)-amine, (-l-)-29], which were well separated, and the former salt was converted into (—)-29, [a] -111.8° (ethanol). Analogously, (+)-29, [a] +110.7° (ethanol), was obtained. ... 

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