Amide formation Acylation reaction that combines polymer-assisted solution-phase microwave chemistry with solid-phase extraction.
{"Image DocumentName": "Amide formationAcylation reaction that combines polymer-assisted solution-phase microwave chemistry with solid-phase extraction.", "Image ImageDescription": "Both synthesis and purification takes < 15 min. 6 different amines were used. HOBt scavenged via Si-carbonate SPE. Recently, Sauer and colleagues have reported an acylation reaction that combines polymer-assisted solution-phase microwave chemistry with solid-phase extraction (SPE), routinely allowing both synthesis and purification to take place in under 15 min. Conventional conditions require rt/16hrs. The reaction of the acid shown with 6 different amines was accomplished using microwave irradiation for 5 min at 100 \uf0b0C; the coupling agents used were polystyrene-bound carbodiimide and 1-hydroxybenzotriazole (HOBt). After completion, the mixture was run through a plug of Si-carbonate (3-4 equivalents), eluting with methanol, to scavenge the HOBt and any unreacted acid, and the desired product was obtained in high purity. Less reactive amines (dibenzylamine) gave lower conversions after 5 min of microwave heating (37 % vs. 98 %). The authors note in the paper that the use of a stir-bar facilitates the suspension of PS-carbodiimide resin and mixing of reactions involving insoluble reagents. And that it does not promote the mechanical degradation of the polymer support. \u2013 pg The authors describe a nice synthetic method using a combination of a microwave-assisted amide coupling using polymer supported carbodiimide with a simple sequestering of HOBt with a silica gel based carbonate. By this combination pure products are available within less than 15 minutes from the start of synthesis. The reaction conditions are amendable to primary, secondary as well as aromatic amines. Noticeable is that amines of low reactivity, such as aniline, provide moderate yields of amides after only five minutes while the overnight reaction at ambient temperature provided less than 10% conversion. D.R. Sauer; D. Kalvin; K.M. Phelan, Org. Lett. 2003, 5,", "Image XResolution": "37", "Image YResolution": "37", "Image ResolutionUnit": "Pixels/Centimeter", "Image Software": "SlidePlayer", "Image YCbCrPositioning": "Centered"}