Catalysis of Organic..

124TEMPO Oxidation of Alcoholsany direct observation regarding the location of each redox cycle in the overallcascade, the schematic is given for illustration purposes only. What we only know isthat removing any of the links in this sequence leads to complete shutdown of theoxidation reaction and as a result, one can speculate that a complete catalytic cycleshould involve transferring of the α-hydrogen from the alcohol molecule in cycle Ato the oxygen in cycle E. In an alternative scenario, the hydrogen and an activatedform of oxygen could interact in either the bromine (C) or the nitrate cycle (D) toproduce HO - . Studies are currently underway to determine the nature of theintermediate species and possibly, the position of the individual cycles in thecascade. Based on the data in Figure 1, one can also say that the bromine cycleproceeds faster than the rate of the TEMPO (B) or the nitrate (D) cycles.Screening for an efficient TEMPO catalyst.A number of commercially available TEMPO derivatives were screened at 16 mmolsubstrate scale at fixed concentrations for X-TEMPO (3.0 mol%), NBS (0.3 mol%)and Mg(NO 3 ) 2 (7.5 mol%). The highest oxidation rates were recorded in the presenceof 5, 3 and 4 (Scheme 3). The N,N - Dimethylamino TEMPO (7) did not performwell and the catalyst system based on this TEMPO derivative deactivated ratherrapidly. The three best performing systems were tested extensively and the results forthe changes in the initial rate of oxygen uptake (curve 3), the conversion of 1 at 60min reaction time (curve 1) and the selectivity to 2 (curves 2) are plotted in Figure 2.In all three instances the initial rate of oxygen uptake is first order dependant on theconcentration of the X-TEMPO catalyst in the 0-5 mmol range and shows a trend tosaturation at high concentrations, clearly indicating that the TEMPO cycle (D) ismost likely the rate limiting step in the overall reaction cascade, presented in Scheme2. At comparable catalyst concentrations, the AA-TEMPO based catalystcomposition (Fig 2c) is nearly twice as active than the one based on MeO-TEMPO(2a) or TEMPO (2b). For example, to attain the maximum rate in the oxygen uptakefor a full conversion of 1, the MeO-TEMPO and the TEMPO based systems require1.25mmol catalyst (7.8 mol%) while the AA-TEMPO system reached its maximumperformance at 0.6mmol level (3.7 mol%).NHCOCH 3OMeOHO(CH 3) 2N.ONO . NO.AA-TEMPO (5) > TEMPO (3) > MeO-TEMPO (4) > HO-TEMPO (6) >> DMA-TEMPO (7)Scheme 3.Another interesting observation from the data in Figure 2 was the effect of thecatalyst concentration on the aldehyde selectivity (curves 2 in 2a-c). As mentionedearlier, at this moderate reaction temperature, the only by-product present inmeasurable quantities was hexanoic acid, formed as a product of the over-oxidationof 2. Contrary to what was reported in the literature for other TEMPO basedoxidations of alcohols (20,21), the current catalyst system, particularly at higherN.ON.O