Amine-imine exchange reactions

Imine metathesis is often carried out at high temperature using a metal-based catalyst. However, amine-imine exchange reactions of sterically unhindered reactants have been shown to proceed rapidly in non-aqueous organic solvent systems without such catalysts, or acids. Ab initio gas-phase calculations suggest that such... 

In 1992, Goodwin and Lynn reported the first example of template-directed synthesis of DNA analogs via formation of a reversible imino linkage [21]. Five years later, Hue and Lehn described the first use of the reaction of imine condensation for the selection, by DCC, of carbonic anhydrase inhibitors from a library of amines and aldehydes [8], Upon addition of the enzyme, the formation of one library component was strongly amplified when compared to a similar reaction carried out in the absence of template. Since then, imine exchange reaction has been applied... 

Reductive -elimination of A3-iodanes on carbon atoms (M = C) produces C-C double bonds, while that on oxygen and nitrogen atoms (M = O and N), combined with the initial ligand exchange reaction, provides a method for oxidation of alcohols and amines to the corresponding carbonyl compounds and imines, respectively [Eq. (26)]. 

Scheme 11 Model reversible aminonitrile reactions exchange reactions with (a) imine and (b) amine...

Farnum, M., Palcic, M., and Klinman, J. P., 1986, pH dependence of deuterium isotope effects and tritium exchange in the bovine plasma amine oxidase reaction a role for single base catalysis in amine oxidation and imine exchange. Biochemistry, 25 1898n 1904. 

Amine Exchange Reaction of a g-Keto Imine with an Amine in the Presence of a Metal Ion... 

Amine-exchange reaction. Unsymmetrical secondary and tertiary amines can be synthesized by dehydrogenation of primary or secondary amines by palladium black (25-200°, 3-20 hr.). The initial step is considered to involve dehydrogenation to an imine followed by addition of the amine and elimination ... 

Under acidic conditions, the desired amine formed is immediately protonated to give an ammonium salt, which is inhibited from participating in the amine exchange reaction. With added ammonia the intermediate imine will only participate in the exchange of nitrogen with the excess ammonia until its ultimate reduction to the primary amine. It is therefore possible to prepare mixed alkylamines by the addition of another amine prior to hydrogenation (Scheme 31). ... 

Bidentate coordination of the imine was also demonstrated in crystal structures of Ir(i) bis(ethylene) and 1,5-cyclooctadiene complexes. An analogous chelate iridium-amine adduct was also synthesized and structurally characterized. The kinetics of substitution of amine by imine (Scheme 14) were investigated to probe the mechanism of the product/substrate exchange reaction in the proposed catalytic cycle. The data were interpreted in terms of an associative mechanism in which the imine binds reversibly to Ir, prior to the release of amine. However, since the catalytic mechanism may well involve octahedral Ir(m) rather than square-planar Ir(i) complexes, a different mechanism could well operate during catalysis. 

The formation of bicyclic imines (263,264) from piperidine enamines and y-bromopropyl amines may appear at first sight to be a simple extension of the reactions of enamines with alkyl halides. However, evidence has been found that the products are formed by an initial enamine exchange, followed by an intramolecular enamine alkylation. Thus y-bromodiethylamino-propane does not react with piperidinocyclohexene under conditions suitable for the corresponding primary amine. Furthermore, the enamine of cyclopentanone, but not that of cyclohexanone, requires a secondary rather than primary y-bromopropylamine, presumably because of the less favorable imine to enamine conversion in this instance. 

Phosphorous acid has also been of use for additions to imines. Originally investigated by Moedritzer and Irani,241 who developed a Mannich-type procedure for the preparation of phosphorus-centered species, the approach was found later to be useful for both primary and secondary amines in reaction with formaldehyde and phosphorous acid. The approach was later used for the preparation of a cationic exchange resin using a polymer substrate.242... 

Trimetrexate (88) Is an antineoplastic agent related to the well-established folic acid antimeta-bolite methotrexate. It can be synthesized by selective diazotization of the most basic amino group of 2,4,6-triamino-5-methylquinazoline (85) followed by a Sandmeyer displacement with CuCN to give nitrile 86. Careful reduction asing Raney nickel produces the aminomethyl intermediate 87 or, if the reaction is carried out in the presence of 3,4,5-triniethoxyaniline, trimetrexate (88) [24]. One presumes that that outcome is a consequence of amine exchange at the partially reduced imine stage and further reduction. 

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