Reversible benzylamine

Hexamethylenetetramine. Hexa, a complex molecule with an adamantane-type stmcture, is prepared from formaldehyde and ammonia, and can be considered a latent source of formaldehyde. When used either as a catalyst or a curative, hexa contributes formaldehyde-residue-type units as well as benzylamines. Hexa [100-97-0] is an infusible powder that decomposes and sublimes above 275°C. It is highly soluble in water, up to ca 45 wt % with a small negative temperature solubiUty coefficient. The aqueous solutions are mildly alkaline at pH 8—8.5 and reasonably stable to reverse hydrolysis. 

Another route to the amido complexes originates from [(>j-Tp )W(CO) (PhC=CMe)(OTf)l and benzylamine and yields [(i -Tp )W(CO)(PhC=CMe) (NHCH2Ph)] (96JA6916). The latter can be protonated with tetrafluoroboric acid to give the amine derivative [(> -Tp )W(CO)(PhC=CMe)(NH2CH2Ph)](Bp4), and this process can be reversed by -butyllithium. Hydride abstraction by silver tetrafiuoroborate, molecular iodine, or PhsCPEe leads to the cationic imine derivatives [(> -Tp )W(CO)(PhC=CMe)(HN=CHPh)]". -Butyllithium deproto-nates the product and gives the neutral azavinylidene species [(> -Tp )W(CO) (PhC=CMe)(N=CHPh)]. The latter with silver tetrafiuoroborate forms the cationic nitrile species [(j -Tp )W(CO)(PhC=CMe)(N=CPh)](Bp4). 

This tethered ferrocenyl-based Pd complex on MCM-41 (17) was then used for the catalytic amination reaction between cinnamyl acetate and benzylamine (40 °C, THF) [59]. In this case, confinement of the catalyst results in profound changes in regio- and enantioselectivity. When the homogeneous equivalent is used to catalyze the reaction, the straight chained derivative is the sole product. Similar results (only 2% of the branched product) were obtained when the catalyst was tethered to the surface of the non-porous silica Cabosil. When tethered inside the pores of MCM-41 a major change occurred in that now the branched product accounts for about 50% and a change in e.e. from 49% e.e. when anchored to the Cabosil support to +99% when anchored inside the MCM-41 pore could be observed. If the catalyst s chirality was reversed in the MCM-41 immobihzed case, so was the chirality of the product (measured at 93% e.e.) [60]. 

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>. 

Dideoxynucleosides show potent anti-retroviral activity against HIV-specific reverse transcriptase80-83. In particular, 2, 3 -dideoxy-3 -C-cyano-2 -substituted thymidine derivatives (33 A and 33 B) with a free 5 -hydroxy function (R1 = H) are potential inhibitors of the HIV-reverse transcriptase-promoted c-DNA synthesis. As these compounds have yet to be prepared by another method, the 3 -ene-nitrile 3284 was subjected to conjugate addition reactions with ammonia, primary amines, secondary amines and carbon nucleophiles. Most of these nucleophilic amine addition reactions give either the trans-isomer 33 A as the sole product (e.g., reaction with pyrrolidine, piperidine, morpholine), or as the major product along with the c/s-isomer (e.g., reaction with methylamine, benzylamine), except for the reaction with ammonia where the cts-isomer 33B is formed as the major product84. 

The quantitative addition of benzylamine to 391 provides /S, 0-benzylglyceraldimine (407), which undergoes Grignard addition to afford a mixture of threo-40S and erythro-409 amino alcohols. The product ratio obtained depends on the solvent and metal cation employed. Addition of cerium(III) chloride in THE reverses the stereoselectivity in favor of the erythro adduct 409 [137]. 

All these effects have an important, hitherto mostly neglected influence on drug activity [214]. The differences in inhibitory activities of trimethoprim (TMP) analogs in cell-free and whole cell systems of Escherichia coli strains being sensitive and resistant to TMP, the interaction of amphiphilic benzylamines with artificial bilayers, the interaction of neuroleptics with bilayer membranes (measured by NMR techniques), and the reversal of multidrug resistance by amphiphilic agents could quantitatively be described in relation to these effects [214]. 

Other unsaturated substrate analogs that have been tried as enzyme inhibitors include allyl amine and allyl alcohol. Allylamine is a pseudo-irreversible inhibitor of flavin-linked monoamine oxidase i.e., in the presence of allylamine, the enzyme shows a time-dependent inactivation that cannot be reversed by dialysis. When radiolabeled allylamine is used, radioactivity is incorporated at the same rate as the enzyme is inhibited. However, inhibition is relieved and radioactivity is removed from the enzyme upon incubation with the substrate, benzylamine. 

The regioselectivity of insertion reactions of unsymmetrical ester-activated alkynes with -benzylamine palladacycles was examined resulting in seven-membered palladacycles where the carboxylate group is preferentially located next to the phenyl group. This substitution pattern can be reversed by using electron-deficient and/or coordinatively unsaturated palladium centers. 

Ethylenediamine is probably unique in that it reacts with t-butyl chromone-2 Carboxylate to give a 4-imino derivative [181] this reaction is reversible and is probably explained by the stabilisation of the pyrone ring through hydrogen bonding as shown in (77). It is noteworthy that although t-butyl esters are more resistant than the methyl or ethyl homologues to attack by amines [153], t-butyl chromone-2-carboxylate was recently reported [182] to be converted into an enamine (78) by reaction with benzylamine. 

Dehydrative Condensation of Carboxylic Acids with Amines and Alcohols. For reversible fluorescent labeling of amino groups, ethoxy(trimethylsilyl)acetylene was used as a dehydrating reagent to couple dansylaminomethylmaleic acid (DAM) with benzylamine through a maleic anhydride intermediate (eq 6). ... 

Reaction mechanism Detailed mechanistic studies have been conducted on this reaction. While the stoichiometric protonolysis reaction of [ (ArNCMe)2CH Mg" Bu]2 with benzylamine, 2-methoxyethylamine, and pyrrolidine to yield the corresponding dimeric magnesium amides and methane proceeds rapidly and non-reversibly at room temperature [88], the reaction of [ (ArNCMe)2CH Ca N (SiMe3)2 (THF)] with benzylamine forms a quantifiable equilibrium between monomeric bis(trimethylsilyl)amide and dimeric benzylamide reaction products. A van t Hoff analysis of this equilbrium mixture allowed derivation of AG°(298 K) as —2.7 kcal mol consistent with facile precatalyst activation via protonolysis with a primary amine [76, 87]. 

Jones et al. (67) also prepared a wide range of water soluble ammonium dithiocarbamate salts, [NH4][S2CNR2] (Fig. 5). They result from the iifitial reaction of the amine with concentrated aqueous ammonia in ethanol, followed by later addition of carbon disulfide at low temperatures. For example, diethanolamine, HN(CH2CH20H)2, forms a yellow precipitate in 65% yield. Castro et al. (68) studied the kinetics and mechanism of the reactions of piperidine, pyrrolidine, morpholine, and benzylamine (69) with carbon disulfide in ethanol (Fig. 6). They proceed via a dithiocarbamic acid intermediate (4), which in turn yields the dithiocarbamate anion (5) upon proton loss to the amine. While for pyrrolidine, formation of the dithiocarbamic acid is rate determining and proceeds to the dithiocarbamate irreversibly, for both morpholine and benzylamine, the transformation is reversible. Further, in these cases the ethoxide anion is found to catalyze the transformations. They have also determined that pyrrolidine is 200 times more nucleophilic toward carbon disulfide than piperidine, despite the later being only slightly more basic, a feature that may relate to the irreversible nature of the formation of pyrrolidine dithiocarbamate. 

---