NiSO4·6H2O as a new, efficient, and reusable catalyst for the α-aminophosphonates synthesis under mild and eco-friendly conditions

Abstract

Nickel (II) sulfate hexahydrate is used for the first time as an efficient catalyst for the one-pot synthesis of a-aminophosphonates by three-component condensation reaction of aromatic aldehyde, primary amine, and diethylphosphite under mild and eco-friendly conditions. NiSO 4 Á6H 2 O was used with a catalytic amount of 5 mol% at room temperature, without solvent in the reaction. A series of the desired aaminophosphonates are obtained after a simple work-up procedure, with excellent yields (up to 92 %) within a short reaction time of 10-20 min in all cases. This heterogeneous catalyst was reused several times with the same activity. The present approach offers the advantages of a clean reaction, simple methodology, easy purification, and economic availability of the catalyst. Graphical Abstract NiSO 4 .6H 2 O 5 mol% Neat, rt 10-20 min R 1 H O + P O OEt OEt + NH 2 R 2 P H N R 1 O OEt OEt R 2 R 1 = Aryl, heteroaryl, ect R 2 = H, CH 3 , CF 3

Promiscuous lipase catalyzed a new P–C bond formation: Green and efficient protocol for one‐pot synthesis of α‐aminophosphonates

“…Based on the generally accepted chemically catalyzed mechanism of the Kabachnik‐Fields reaction[12,30] and the literature regarding enzymatic promiscuity to form carbon–carbon bonds,[17a,c,f] a mechanism was suggested for the C–P bond formation starting the interaction with lipase active site of CAL‐B (Scheme ).…”

“…To our delight, the α-aminophosphonate 4a was obtained in 94% yield exclusively under solvent-free conditions at room temperature by catalytic promiscuity in the presence of 50 mg of CAL-B (Table 1, entry 10). Furthermore, there is no reaction in the absence of lipase at 25°C and traces of products appear at 40°C (Table 1, entries 11,12).…”

“…[17f,28] However, the synthesis of αaminophosphonates is carried out under conditions of MCRs by catalysis with a lipase under solvent-free condition which is a synthetic route including biocatalysis, MCRs, neat reaction, the biocatalyst reuse, simple purification without column chromatography, the criteria for a green chemistry process. [29] Based on the generally accepted chemically catalyzed mechanism of the Kabachnik-Fields reaction [12,30] and the literature regarding enzymatic promiscuity to form carboncarbon bonds, [17a,c,f] a mechanism was suggested for the C-P bond formation starting the interaction with lipase active site of CAL-B (Scheme 2).…”

“…The synthesis of α‐aminophosphonates by multicomponent condensation in one pot according to the Kabachnik‐Fields reaction[10] is widely described in the literature with a variety of catalysts [11]. We have recently reported NiSO 4 ·6H 2 O as a new and efficient catalyst for the synthesis of α‐aminophosphonates [12]. However, the use of organometallic catalysts does not satisfy us with the objective to develop biologically active compounds through a greener process.…”

“…[11] We have recently reported NiSO 4 ·6H 2 O as a new and efficient catalyst for the synthesis of α-aminophosphonates. [12] However, the use of organometallic catalysts does not satisfy us with the objective to develop biologically active compounds through a greener process.…”