Aerobic Oxidation of Cycloalkanes, Alcohols and Ethylbenzene
FULL PAPERS
Conclusions
Analysis
The reactions were monitored by gas chromatography using a
CP-WAX 52 CB column (50 m  0.53 mm). A typical temper-
ature program starts at 508C (5 min) with aramp of 88C/min up
to 2208C. The reported yields are thus GC yields and are
determined using 1,2,4-trichlorobenzene as the internal stand-
ard. Molar responses were obtained by calibration of pure
samples against this internal standard. 1,15-Pentadecanoic
acid, 1,12-dodecanedioic acid, 1,10-decanedioic acid and 1,8-
octanedioic acid were analysed by HPLC (Waters Symmetry
C18 reversed phase column, eluent: water/methanol, 50:50,
0.1% TFA) using octanoic acid as an internal standard. The
products reported in the tables, plus the two isomeric
hydroxycyclododecanones and two isomeric cyclododecadi-
enones which have been identified, together account for more
than 90% of the substrate converted.
The NHS/Co combination is an effective catalyst for the
aerobic oxidation of cycloalkanes to the corresponding
cycloalkanones, displaying higher activities than the
previously reported NHPI/Co system. The system was
also applied successfully to the autoxidation of ethyl-
benzene to acetophenone and of a variety of secondary
and primary alcohols to the corresponding ketones and
carboxylic acids, respectively. A mechanistic rationale is
proposed to explain the activities of N-oxyl radicals as
autoxidation catalysts and the different reactivities
observed for NHS and NHPI.
Experimental Section
Acknowledgements
Safety Remarks
This project was financed by Quest International and by the
Dutch Ministry of Economic Affairs under the Innovation
Oriented Projects scheme (IOP Catalysis) and the contributions
are gratefully acknowledged. We thank W. Motherwell for
fruitful discussions. We are also grateful to W. Partenheimer for
his valuable mechanistic discussions.
Aerobic oxidations should always be performed with caution.
In our case with 100% molecular oxygen, we worked above the
explosion limit, and monitored the oxygen uptake by a burette.
Laboratory glassware was used behind safety screens, and the
scale was limited to 10 mL solutions.
References and Notes
Chemicals
The chemicals were obtained from commercial sources and
used as received. N-Hydroxysaccharin (NHS) was synthesised
according to a seven-step synthesis published by Nagasawa
etal. [5] in 1995 with an overall yield of 17%. 1H NMR (DMSO):
d 7.9 8.1 (m, 4H, Harom), 11.2 (b, 1H, NOH); 13C NMR
(DMSO): d 121.5, 125.1, 125.8, 134.7, 135.2, 135.7 (6Carom),
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157.5 (C O).
Typical Catalytic Run
Experiments were carried out in a two-necked 25-cm3 round-
bottom flask containing a magnetic stirrer, equipped with a
condenser and connected to a gas burette filled with molecular
oxygen. In a typical experiment 504 mg (3 mmol) of cyclo-
dodecane, 60 mg (0.3 mmol) of N-hydroxysaccharin, 5.3 mg
(0.015 mmol) of Co(acac)3 and 200 mg of 1,2,4-trichloroben-
zene were weighed in the flask before addition of 7.5 mL acetic
acid or 9 mL of acetic acid. A series of vacuum/molecular
oxygen purges were applied before the reaction was started.
The resultant mixture was stirred at a temperature of 808C for
10 hours.
For 2-octanol oxidation in a typical experiment 585 mg 2-
octanol (4.5 mmol), 90 mg (0.45 mmol) of N-hydroxysacchar-
in, 8 mg (0.022 mmol) Co(acac)3, 27.5 mg (0.022 mmol) of
benzoic acid and 200 mg of 1,2,4-trichlorobenzene were
dissolved in 7.5 mL solvent, followed by oxygen purges. The
resultant mixture was stirred at a temperature of 1008C for 5 h.
For other substrates conditions are listed with the tables.
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Adv. Synth. Catal. 2004, 346, 286 296
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