A- benzylamines

Further illustration for the lack of structural specificity required for antihistaminic activity comes from the finding that ethylenediamines carrying both a benzylamine and an additional aromatic substituent on one of the nitrogens afford a series of useful therapeutic agents. Alkylation of benzylaniline with JV-... 

Nickel in the presence of ammonia is often used for reduction of nitriles to primary amines. The reaction is done at elevated temperatures and pressures ( 100 C, 1000 psig) unless massive amounts of nickel are used. Cobalt is used similarly but mainly under even more vigorous conditions. Nitriles containing a benzylamine can be reduced over Raney nickel to an amine without hydrogenolysis of the benzyl group (7). A solution of butoxycarbonyl)-3-aminopropyl]-N-<3-cyanopropyl)benzylamine (13.6 g) in 100 ml of ethanol containing 4 g. NaOH was reduced over 3.0 g Raney nickel at 40 psig for 28 h. The yield of A/ -benzyl-Air -(f-butoxycarbonyl)s >ermidine was 95% (7). 

Vinyl sulfonamides of furan-containing A -benzylamines cyclize at room temperature to give 6-sultams with high diastereoselectivity (Scheme 4, <96SL741>). 

In 1997 the first asymmetric aza-Claisen rearrangement was reported by Overman et al. [55], which made use of diamines as bidentate ligands for Pd(II), allowing for moderate enantioselectivities. In the same year, Hollis and Overman described the application of the planar chiral ferrocenyl palladacycle 38 as a catalyst for the enantioselective aza-Claisen rearrangement of benzimidates 39 (Fig. 19) [56]. A related ferrocenyl imine palladacycle provided slightly inferior results, while a benzylamine palladacycle lacking the element of planar chirality was not able to provide any enantioselectivity [57]. 

Butenafine hydrochloride (Mentax) is a benzylamine that is structurally related to the allylamines. As with the allylamines, butenafine inhibits the epoxidation of squalene, thus blocking the synthesis of ergosterol, an essential component of fungal cell membranes. Butenafine is available as a 1% cream to be applied once daily for the treatment of superficial dermatophytosis. 

In many reactions, the dihydro compounds resemble their aliphatic analogues. Thus, when Z is nitrogen, (225) behaves as a benzylamine, (223 Z = NH) as an aromatic amine, and (226) as a Schiff s base. Similar comparisons apply when Z is oxygen or sulfur (223 Z = 0) is an aromatic ether, (225 Z = 0) is a dibenzyl-type ether, and (223 Z = S) is an aromatic sulfide. Some of this behavior is illustrated by the following examples. 

Table 3.9. Acidolytic cleavage of resin-bound A-benzylamine derivatives.

The structure of MDA can be viewed as an aromatic ring (the 3,4-methylenedioxyphenyl ring) with a three carbon chain sticking out from it. The amine group is on the second of the three carbon atoms. The isomers, with the amine function moved to the first of these carbons atoms (a benzylamine) and with the amine function moved to the third (furthest out atom) of these carbon atoms (a (n)-propylamine), are known and both have been assayed. 

To this end, we have designed a new range of salts [AH][H2POJ (17). combining a cation derived from an organic amine (e.g. A = benzylamine,... 

Feeding experiments with doubly labeled 3-hydroxy-4-[14C]methoxy-A-meth-yl-(f -[3H]- and -(5)-[3H]A,-benzylamines in King Alfred daffodils produced oduline (186) with high (82-85%) tritium retention (139). This observation suggested that the incorporation of A-methylisovanillamine into 186 occurred by a nonstereospecific process in which hydrogen removal from the benzylic position was governed by a kinetic isotope effect. 

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

The parallelism in reactions with HMPT and mixtures of phosphorus pentoxide and amines can best be realized by looking at the mechanism of HMPT reactions [1 5 ]. In the reaction of p-methoxy-benzylalcohol with HMPT which produce the corresponding N,N-dimethylbenzyl amine--p-methoxybenzyl phosphate was identified in the XP NMR spectrum of the reaction mixture. Since pyrophosphate was also observed during the reaction of the benzyl alcohol with HMPT, the intermediate formation of the metaphosphate anion can be assumed. Addition of the benzyl alcohol to that anion then produce the benzyl phosphate. Phosphate ions are known to be good leaving groups so that a benzylamine can easily be produced from the phosphate by reaction with di-methylamine released from the dimethylammonium ion. The phosphoric acid produced during the reaction is believed to react with HMPT, so that more dihydro-gen-bis(dimethylammonium) pyrophosphate is formed. 

A mixture of furfurylbenzyl ketone and of N-ethyl-a-benzylamine in methanol was hydrogenated over Raney nickel at 150°C and at a pressure of 1500 p.s.i. The catalyst was removed by filtration and the solvent removed by vacuum distillation. The oily residue was taken up in ether, the ether solution washed with dilute hydrochloric acid and the aqueous layer separated. Addition of 35% sodium solution caused the separation of an oil which was taken up in ether. Removal of the ether by evaporation followed by distillation of the residue gave N-ethyl-a-benzyltetrahydrofurfurylamine, boillin point 101°C/0.07 mm. 

Various imines and imine precursors reacted with immobilized ester-enolate-derived triazene esters 481 to give polymer-bounded azetidin-2-ones 482 (Scheme 68). The esters were bound to a benzylamine resin by a triazene linker employing diazonium salts. Traceless cleavage from the triazene linker yielded the desired azetidin-2-ones 483 <2002JOC8034>. 

Fig. 3.9 Decrease in the transition temperature ofDPPAby phenylalkylamines (a) benzylamine,...

In rivastigmine (see Fig. 12.5), which was modeled in miotin s skeleton, the tricyclic eseroline of physostigmine is simplified into a benzylamine system. As detailed above, Stedman found that the m-Me2N-CH(CH3)-aryl derivative (miotin ... 

Show how Gabriel syntheses might be used to prepare the following amines, (a) benzylamine (b) hexan-1-amine (c) y-aminobutyric acid... 

The second route [Eqs. (18) and (19)] involves the condensation of a benzylamine with glyoxal semiacetal. This was devised by Schlittler and Muller41 as an improvement on the Pomeranz-Fritsch synthesis.1... 

Fig. 9.29. (a) Retention of (S)-phenylalanine-anilide, (5)-(lK and enantioselectivity (a) for the separation of H.SX ) on a (5)-(l) imprinted polymer at different mobile pha.se pH-values. (b) Comparison of calculated (dashed lines) and experimental (solid lines) pH-retention curves for (/(,5)-(l( and benzylaminc on a benzylamine-selective polymer (reprinted with permission from Ref. 3b()l). 

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