Amines are susceptible to oxidation. Tertiary amines are oxidized to give N-oxides.
Secondary amines having proton(s) at the α-position are oxidized to nitrones. The conversion to hydroxylamines is possible depending on the conditions.
The oxidation of heterocyclic amines such as pyridine requires more forcing conditions. In these cases, oxidants such as trifluoroperacetic acid and methyltrioxorhenium(VII) are effective.
Synthesis of a nitrone using catalytic MeReO3.
A250-mL, two-necked, round-bottomed flaskequipped with amagnetic stirbar,thermometer, and areflux condenserfitted with arubber septumand balloon of argon is charged with a solution ofmethyltrioxorhenium(MTO) (0.013 g, 0.05 mmol, 0.1% mol equiv)in100 mL ofmethanol.Urea hydrogen peroxide(UHP) (14.3 g, 152 mmol)is added, the flask is cooled in anice bath, anddibenzylamine(9.7 mL, 50.7 mmol)is then added dropwise viasyringeover 10 min. After completion of the addition, theice bathis removed and the mixture is stirred at room temperature. A white precipitate forms after approximately 5 minand the yellow color disappears within 20 min. Another four portions ofMTO (0.1% mol equiv, 0.013 geach) are added at 30-min intervals (2.5 hr total reaction time). After each addition, the reaction mixture develops a yellow color, which then disappears; only after the last addition does the mixture remain pale yellow. The reaction flask is cooled in anice bathand solidsodium thiosulfate pentahydrate(12.6 g, 50.7 mmol)is added in portions over 20 min in order to destroy excesshydrogen peroxide. The cooled solution is stirred for 1 hr further, at which point a KI paper assay indicates that the excess oxidant has been completely consumed. The solution is decanted into a 500-mL flask to remove small amounts of undissolvedthiosulfate. The solid is washed with50 mL of MeOHand themethanolextract is added to the reaction solution which is then concentrated under reduced pressure by rotary evaporation.Dichloromethane(250 mL)is added to the residue and theureais removed by filtration through cotton and celite. Concentration of the filtrate affords10.3 g(97%) of thenitroneas a yellow solid. If desired, thenitronecan be recrystallized fromdiisopropyl ether(200 mL), affording9.0 g(84%) of a white solid. Concentration of the mother liquor and recrystallization of the residue from40 mL ofdiisopropyl etherprovides0.600 gof additionalnitrone. Total yield:9.6 g(89%) of thenitroneas a white solid.