Mechanism transimination

In the course of the catalytic hydrogenation of a,us dinitriles over Raney nickel, by-products are obtained from C-N and C-C bond formation. The mechanism of the formation of these compounds was investigated. Cyclic and linear secondary amines can result from the same secondary imine through a transimination process involving a ring-chain tautomerism. Stereochemical results for 2-aminomethyl-cyclopentylamine (AMCPA) are in accordance with a specific cyclisation pathway favored by an intramolecular hydrogen bond giving rise to the cis isomer from aminocapro-nitrile, unfavored in the case of adiponitrile which leads to the trans AMCPA as the major isomer. 

In the early 1960s, seminal work by Jencks and coworkers demonstrated that formation and hydrolysis of C=N bonds were proceeding via a carbinolamine intermediate, thus leading to a more general mechanism of addition reactions on carbonyl groups [17-19]. The dynamic nature of the reaction of imine formation can be exploited to drive the equilibrium either forward or backwards. Since the reaction involves the loss of a molecule of water, adding or removing water from the reaction mixture proved an efficient way to shift the equilibrium in either direction. The responsive behavior of imines to external stimuli makes the reversible reaction of imine formation perfectly suited for DCC experiments [20], Thermodynamically controlled reactions based on imine chemistry include (1) imine condensation/hydrolysis, (2) transiminations, and (3) imine-metathesis reactions... 

Schnackerz et al. (1979). The same adduct was isolated from glutamate decarboxylase following inactivation with serine O-sulfate (Likos et al., 1982). The mechanism proposed to account for this observation involves elimination of sulfate from the inactivator followed by transimination with the active site lysine of the enzyme (Fig. 9). The released aminoacrylate then rotates in the active site and acts as a nucleophile, attacking the electrophilic imine. Under basic conditions the enzyme lysine is eliminated, generating the free cofactor adduct. This reaction is therefore unusual in that the inactivator is ultimately the nucleophilic partner in the inactivation reaction, in contrast to all of the reactions described to this point, in which the enzyme provides the nucleophile. 

Equation (40) is known as a transimination or a trans-SchifSza-tion reaction. It probably proceeds via a two-step mechanism involving a m-diamine intermediate, analogous to the carbinolamine intermediate observed in imine formation fix>m carbonyl compounds. The transimination reactions of Schiff bases derived from either aliphatic or aromatic amines with semicarbazide, hydroxylamine or methoxyamine, of oximes with semicarbazide and of semicarbazones with hydroxylamine all appear general base catalyzed in terms of one protonated and one free base reactant or general acid catalyzed in terms of two reactants of free base. These results may be accounted for by a nearly symmetrical mechanism for transimination (equations 41 and 42). Simple proton transfers are considered to be rapid and... 

FIGURE 20.3 Mechanism of the transimination reaction of a PLP-enzyme imine with an a-amino acid to give a PLP-amino acid imine plus expelled enzyme. The reaction is analogous to that shown previously in Figure 14.8. 

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