Abstract
The Kabachnik–Fields (phospha-Mannich) reaction involving the condensation of primary or secondary amines, oxo compounds (aldehydes and ketones) and >P(O)H species, especially dialkyl phosphites, represents a good choice for the synthesis of α-aminophosphonates that are of significant importance due to their biological activity. In general, these three-component reactions may take place via an imine or an α-hydroxy-phosphonate intermediate. The monitoring of a few Kabachnik–Fields reactions by in situ Fourier transform IR spectroscopy has indicated the involvement of the imine intermediate that was also justified by theoretical calculations. The Kabachnik–Fields reaction was extended to >P(O)H species, comprising cyclic phosphites, acyclic and cyclic H-phosphinates, as well as secondary phosphine oxides. On the other hand, heterocyclic amines were also used to prepare new α-amino phosphonic, phosphinic and phosphine oxide derivatives. In most cases, the synthesis under solvent-free microwave (MW) conditions is the method of choice. It was proved that, in the cases studied by us, there was no need for the use of any catalyst. Moreover, it can be said that sophisticated and environmentally unfriendly catalysts suggested are completely unnecessary under MW conditions. Finally, the double Kabachnik–Fields reaction has made available bis(phosphonomethyl)amines, bis(phosphinoxidomethyl)amines and related species. The bis(phosphinoxidomethyl)amines serve as precursors for bisphosphines that furnish ring platinum complexes on reaction with dichlorodibenzonitriloplatinum.
Highlights
The basic method for the preparation of -aminophosphonates, valuable synthetic equivalents and biologically active substrates, involves the condensation of a primary or secondary amine, a carbonyl compound and dialkyl phosphite (Scheme 1) [1,2].Scheme 1
The monitoring of a few Kabachnik–Fields reactions by in situ Fourier transform IR spectroscopy has indicated the involvement of the imine intermediate that was justified by theoretical calculations
A lot of catalytic variations to carry out three-component Kabachnik–Fields condensations have been described, we found that the most straightforward synthesis is when the reactants are irradiated with microwave (MW) in the absence of any catalyst or solvent
Summary
The basic method for the preparation of -aminophosphonates, valuable synthetic equivalents and biologically active substrates, involves the condensation of a primary or secondary amine, a carbonyl compound (aldehyde or ketone) and dialkyl phosphite (Scheme 1) [1,2]. -Aminophosphonic acids, considered as phosphorus analogues of -amino acids, have attracted much attention in drug research due to their low mammalian toxicity. They are important targets in the development of antibiotics, antiviral species, antihypertensives, and antitumour agents based on their effect as inhibitors of GABA-receptors, enzyme inhibitors and anti-metabolites [3,4,5,6,7,8,9]. Certain -aminophosphonates were proved to be suitable for the design of continuous drug release devices due to their ability to increase the membrane permeability of a hydrophilic probe molecule [14]
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