Continuous flow synthesis of α-aryl-α-aminophosphonates

Abstract

The synthesis of α-aryl-α-aminophosphonates was performed by the three-component Kabachnik-Fields reaction of primary amines, benzaldehyde derivatives and dialkyl phosphites in a continuous flow microwave reactor. The target compounds could be obtained in high (~90%) yields without any catalyst in simple alcohols as the solvent. The flow process elaborated required shorter reaction times and lower excess of the reagent, as compared to the “traditional” batch reactions, and allowed the synthesis of the α-aminophosphonates on a somewhat larger scale.

Study on the Microwave-Assisted Batch and Continuous Flow Synthesis of N-Alkyl-Isoindolin-1-One-3-Phosphonates by a Special Kabachnik–Fields Condensation

“…In the last decade, various applications of the continuous flow MW technique were reported; however, in most cases non-professional MW reactors were applied, in which the parameters cannot be measured accurately [28]. In our previous work, we introduced a MW-assisted continuous flow synthesis of simple α-aryl-α-aminophosphonates by the three-component Kabachnik−Fields reaction [29], which may mean a good starting point towards the development of special condensation-ring closure reactions in continuous flow. In this paper, at first, the catalyst-and solvent-free condensation of 2-formylbenzoic acid, aliphatic primary amines and various >P(O)H reagents was studied in a batch MW reactor.…”

“…The continuous flow reactions were performed in a self-developed continuous flow system comprising a 300 W CEM Discover (CEM Microwave Technology Ltd., Buckingham, UK) focused microwave reactor equipped with a CEM 10 mL Flow Cell Accessory continuous flow unit (irradiated volume 7 mL) [29,33,34]…”

“…The continuous flow reactions were performed in a self-developed continuous flow system comprising a 300 W CEM Discover (CEM Microwave Technology Ltd., Buckingham, UK) focused microwave reactor equipped with a CEM 10 mL Flow Cell Accessory continuous flow unit (irradiated volume 7 mL) [29,33,34], a Gilson 332 dual HPLC pump (Gilson U.K., Bedfordshire, UK), an HPLC backpressure regulator with a 250 Psi (17.2 bar) cartridge (CEM Microwave Technology Ltd., Buckingham, UK) and a cooler. Teflon ® PFA tubes (DuPont, Wilmington, DE, USA) with outside diameter 0.125" (3.175 mm) and inside diameter 0.064" (1.575 mm) were used.…”

Continuous Flow Organophosphorus Chemistry

“…Following a preliminary report, [40] Bálint, Keglevich and coworkers studied the catalyst-free synthesis of various α-aryl-αaminophosphonates under microwave-assisted continuous flow conditions according to a three-component Kabachnik-Fields reaction. [73] Optimization of the system was performed using a model reaction involving aniline, benzaldehyde and diethyl phosphite in a batch MW reactor. Irradiating the cell for 30 min at 100°C with 3 equiv.…”

“…from cyclohexyl-and butylamine, respectively). For these experiments, side-products such as the corresponding [73] EurJOC European Journal of Organic Chemistry α-hydroxyphosphonate (select. 43-53 %) and the intermediate imine (select.…”