Benzylamine hydrochloride, preparation

Aqueous aza-Diels-Alder reactions of chiral aldehydes, prepared from carbohydrates and with benzylamine hydrochloride and cyclopentadiene, were promoted by lanthanide triflates (Eq. 12.65).137 The nitrogen-containing heterocyclic products were further transformed into aza sugars, which are potential inhibitors against glycoprocessing enzymes. 

Only one preparation of this ring system has been reported. This preparation involves the interesting reaction of compound (248) with benzylamine hydrochloride and formaldehyde to give the cyclized product (249) (70M1824). 

The alkylation of the [2-(l//-tetrazol-5-yl)benzyl]carbamic acid r/-butyl ester with Mel in DMF in the presence of K2C03 has been studied <2004JME2995>. A mixture of regioisomers was separated and purified by reverse-phase preparative ffPLC. 2-(l-Methyl-l//-tetrazol-5-yl)benzylamine hydrochloride and 2-(2-methyl-2//-tetrazol-5-yl)ben-zylamine hydrochloride formed under these conditions in a ratio 1 1.5 <2004JME2995>. 

A modification of the Sommelet reaction (see page 339) is to convert primary and secondary benzylamines into aldehydes by means of formaldehyde and hexamethylenetetramine. For instance, Greymore and Davies obtained benzaldehyde from benzylamine hydrochloride by this route 593 and 2-fluorene-carbaldehyde has been similarly prepared in 70% yield from 2-(aminomethyl)-fluorene hydrochloride.594 Papers by Snyder et al.595 and by M. M. Robison and B. L. Robison596 should be consulted for the reaction of tertiary amines with hexamethylenetetramine. Benzaldehydes can be synthesized by treating benzylamines with sodium nitrite and trifluoroacetic acid (molar ratio 1 2 3)... 

SYNTHESIS To a suspension of 18.6 g benzylamine hydrochloride in 50 ml warm MeOH there was added 2.4 g of 3,4-methylenedioxyphenylacetone (see under MDMA for its preparation) followed by 1.0 g sodium cyanoborohydride. Concentrated HCI in MeOH was added [3D. mol structure] several days as required to maintain... 

The 1,3-proton shift reaction has also been applied to the synthesis of a-(perfluoroalkyl)-a-amino acids, specifically 3.3,3-trifluoroalanine.2 -26 Attempts to prepare the A-benzylimine of ethyl 3,3.3-trifluoro-2-oxopropanoate by direct condensation with benzylamine were very difficult due to the exceptionally high stability of the intermediate a-amino alcohol, which fails to dehydrate. By contrast, 1-phenylethanamine reacted with ethyl 3,3,3-trifluoro-2-oxo-propanoate to form ketimine 33 in 83 % yield.26 The 1,3-proton shift reaction of 33 is much faster than those of ketimines derived from perfluoroalkyl ketones or perfluoroaldehydes (see Table 5). Complete conversion in triethylamine required 6 hours at room temperature and afforded the isomeric Shiff base 34 in 92 % yield. Mild hydrolysis of Shifif base 34 gives a-amino ester 35, which in turn hydrolyzes to 3,3,3-trjfluoroalanine hydrochloride (36). 

The optical isomers of DOM have been prepared in two ways. The racemic base has been resolved as the ortho-nitrotartranilic acid salt by recrystallization from EtOH. The (+) acid provides the (+) or S isomer of DOM preferentially. Also, the above-mentioned l-(2,5-dimethoxy-4-methylphenyl)-2-propanone can be reductively aminated with optically active alpha-methyl benzylamine with Raney Nickel. This amine is isolated and purified by recrystallization of the hydrochloride salt. When optically pure, the benzyl group was removed by hydrogenolysis with palladium on carbon. The mp of either of the optical isomers, as the hydrochloride salts, was 204-205 °C. 

Similarly, (S)-fi-tyrosine hydrochloride is prepared by addition of the lithium amide of N-[(R)-l-phenylethyl]benzylamine to methyl ( )-3-[(4-benzyloxy)phenyl]-2-propenoate and subsequent hydrogenolysis and saponification24. Recently, a number of publications concerning related work has appeared139-146. The reaction of lithiated, mono-silylated 1-phenylethyl-amines with a-enones has also been studied130131. 

Sample preparation Mix 1 mL 100 jj-g/mL compound in dichloromethane with 300 pL 100 xg/mL 1-hydroxybenzotriazole in dichloromethane pyridine 99 1, 300 pL 1.1 mg/mL l-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride in dichloromethane, and 300 pL 300 pg/mL benzylamine in dichloromethane, vortex, let stand at room temperature for 1.5 h, evaporate to dryness under a stream of nitrogen, reconstitute the residue in 500 pL MeOH, inject an aliquot. 

Calibration curves were prepared daily for each compound determined. Anhydrous ammonia was injected with a calibrated 1000 ul gas tight syringe through the septum inlet of the reaction tube. Ambient temperature and pressure corrections were made to determine the actual amount of gas injected. Benzylamine was generated from reaction of the hydrochloride salt with potassium hydroxide. The diamine standards were weighed into boats, covered with caustic reagent and volatilized by moving the boat into the heated fiimace. In each case, the standard compounds were trapped and... 

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