Chemoselective N-acylation via condensations of N-(benzoyloxy)amines and alpha-ketophosphonic acids under aqueous conditions.
A new amide-forming reaction with N-benzoyloxyamines and alpha-ketophosphonic acids was investigated. A mixed solvent of t-BuOH/water (1:1) at 40 degrees C provided the desired amide in high yield (71-96%). Both phosphonic acids ( 9, 12, or 13) and their disodium salts (e.g., 10) were shown to react with the respective N-benzoyloxyamines ( 1b and 4) in excellent yields. The phosphonic acid methyl ester monosodium salt 11 did not react under these conditions. However, compound 11 did provide the desired amide in 22% yield upon addition of 2 equiv of TFA. The N-acylation reaction is highly chemoselective for N-benzoyloxyamines as both aliphatic amines and N-hydroxylamines were shown not to react productively with the alpha-ketophosphonic acids under the conditions tested. Moreover, the alpha-ketophosphonic acids are more selective than the related alpha-ketocarboxylic acid systems, which react with both the N-hydroxylamines and N-benzoyloxyamines. In this regard, this novel phosphonic acid methodology provides a new high-yielding, chemoselective acylating reagent for further study.
Arora
Jasbir Singh
JS
Department of Medical Education, College of Medicine, University of Central Florida, Orlando, Florida 32816-2201, USA.
Kaur
Navneet
N
Phanstiel
Otto
O
D000215:Acylation; D000577:Amides / Q000138:chemical synthesis*; D000588:Amines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000577:Amides; D000588:Amines; D007659:Ketones; D063065:Organophosphonates; D014867:Water