Three component coupling catalyzed by TaCl5–SiO2: synthesis of α-amino phosphonates

The synthesis of α-aminophosphonates on a large scale is not always straightforward. One of the described methodologies has now been adjusted for use in a microreactor system. The CPC College System was used to investigate the continuous production of α-aminophosphonates. This technology couples miniaturisation to optimal reaction conditions for the production of chemical and pharmaceutical intermediates. The reaction of an imine with a dialkyl phosphite in different solvents was optimised, since the use of a solvent is necessary when using a microreactor. When methanol was used, a considerable reduction of the reaction time was noticed in comparison with other commonly used solvents. Subsequently, several reaction parameters were optimised in batch and compared with the continuous process in the microreactor. Similar yields and purities were obtained compared to the batch reaction. Using the microreactor system, the scale-up problems were avoided and large amounts of α-aminophosphonates could be generated in a short time.

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Straightforward continuous synthesis of α-aminophosphonates under microreactor conditions

Meenen¹,

Moonen²,

Acke³

et al. 2005

“…The different influence of sterically hindered Nsubstituents however, indicates the involvement of differing reaction pathways or intermediates. In an attempt to eliminate the use of preformed aldimines, the possibility that the above described tandem 1,4-1,2-addition operates under typical Kabachnik-Fields-type, [29][30][31][32][33] threecomponent reaction conditions were investigated. The method reported by Kudrimoto and Bommena was selected as a model.…”

Section: Methodsmentioning

confidence: 99%

On the discovery and development of tandem 1,4- and 1,2-addition of phosphites to 1-azadienes

Waes¹,

Debrouwer²,

Heugebaert³

et al. 2014

Over the past 15 years we have developed a one-step protocol for the synthesis of 3-phosphonylated aminophosphonates from α,β-unsaturated imines through tandem 1,4-1,2-phosphite addition. This account covers the initial development, mechanistic implications of using different phosphite nucleophiles and the expansion towards oximes, hydrazones and unsaturated imines included in aromatic sextets, e.g. quinolines, phenanthrolines and napthyridines.

“…Various synthetic methods for α-aminophosphonic acids and α-aminophosphonates have been reported [14][15][16][17][18][19][20][21][22] and the most straightforward one is the addition of compounds containing a P−H bond to the C=N bond of imines (the Pudovik reaction) (Scheme 1). 23 However, the most useful pathway to the synthesis of α-aminophosphonates is the Kabachnik-Fields reaction, [24][25][26][27] which is a one-pot, three-component procedure using carbonyl compound, amine and dialkyl phosphite (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

Synthetic methods of cyclic α-aminophosphonic acids and their esters

Ali¹

2013