Solvent effects Kabachnik-Fields reaction

The Kabachnik-Fields reaction is an effective means of preparing biologically active a-amino phosphonates [64]. It involves the three component reaction of an aromatic aldehyde, an aniline, and diethylphosphite. The reaction has recently been performed using microwave irradiation with [BMIM]PF6, [BMIM]SbF6, [BMIM]BF4, and DMF as solvents and lanthanide triflates as catalysts (Scheme 7.18) [65]. The reactions were performed using a domestic microwave oven and pulsed irradiation. Catalyst activity in the ionic liquids was found to be higher than or comparable with that in DMF. It was also found that catalyst activity varied depending on the ionic liquid used. For example, Yb(OTf)3 was very active in [BMIM]BF4 but Sc(OTf)3 was more active in [BMIMjPFe. Excellent product yields were obtained. 

Substituent and solvent effects on the Kabachnik-Fields reaction of the dialkyl hydrogenphosphite-cyclohexylamine-benzaldehyde system have been reported kinetic analysis shows evidence of a hydroxyphosphonate intermediate. Kinetics are also reported for several substituted benzaldehydes, probing for evidence of an alternative imine intermediate, and for salicylaldehyde, which does proceed via an imine (as the hydroxyphosphonate is unstable). When the dialkyl hydrogenphosphonate reactant is changed to a phosphonate, the rate and mechanism of the reaction are significantly altered. ... 

In the same year, Shaterian et al. also reported an eco-friendly and novel method for the synthesis of a series of such compounds from a one-pot three-component Kabachnik-Fields reaction employing nano-TiOz as an efficient and reusable heterogeneous catalyst under ambient and solvent-free conditions (Scheme 10). The method is effective and provides excellent yields of the products in a short reaction time, which makes this protocol a novel, environmentally friendly, and economically valuable process for the synthesis of this class of compounds. 

The Kabachnik-Fields (phospha-Mannich) reaction has been reviewed, including evidence for imine intermediates via in situ FT-IR studies. Solvent-free microwave conditions are particularly effective, with little call for catalysts. 

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