F. Yang et al. / Tetrahedron 60 (2004) 1225–1228
1227
The mechanism for the aerobic oxidation of substituted
toluenes catalyzed by cobalt(II) compounds has been
proposed.7,10,13,14 It is suggested that Co(II) reacts with
dioxygen to generate a liable dioxygen complex of super-
oxocobalt(III) or m-peroxocobalt(III) complex. These
cobalt-oxygen species, which were reported to be easily
formed by the one-electron reduction of dioxygen using
cobalt(II),15,16 assist the generation of the radical from
AIBN at high temperature. Bromide, a promoter, may form
Brz radical at low catalyst concentration to initiate the
reaction.10
through the solution for 3 h. After the reaction was finished,
the mixture was cooled to room temperature and
p-methoxybenzoic acid was precipitated. The crude product
was recrystallized with ethanol/water. Then 2.3 g of
p-methoxybenzoic acid was obtained and the yield was
94%, mp 183–184 8C [lit.18 184 8C].
3.3.3. p-Fluorobenzoic acid. 4-Fluorotoluene was oxidized
to give 4-fluorobenzoic acid as a white solid, mp 184–
186 8C [lit.19 185 8C].
3.3.4. p-Chlorobenzoic acid. Oxidation of 4-chlorotoluene
gave 4-chlorobenzoic acid as a white solid, mp 240–242 8C
[lit.20 243 8C].
In conclusion, we have developed a practical procedure for
the catalytic oxidation of substituted toluenes to correspond-
ing aromatic acids in non-acidic solvent of halobenzenes
under atmospheric pressure in the presence of a radical
initiator. It is noteworthy that the reaction systems are
applicable for the oxidation of both electron-withdrawing
and electron-donating substituted toluenes.
3.3.5. Cyanobenzoic acid (p-, m-, o-). p-Cyanotoluene,
m-cyanotoluene and o-cyanotoluene were oxidized with
molecular oxygen catalyzed by system B to give p-cyano-
benzoic acid, m-cyanobenzoic acid and o-cyanobenzoic
acid as white solids, respectively. p-Cyanobenzoic acid: mp
217–218 8C [lit.21 219 8C]; m-cyanobenzoic acid: mp 215–
216 8C [lit.21 217 8C]; o-cyanobenzoic acid: mp 187–
188 8C [lit.22 187 8C].
3. Experimental
3.1. General remarks
3.3.6. p-Phthalic aid. Oxidation of p-xylene catalyzed by
system A gave p-phthalic aid as a white solid, 96% yield.
Sublimes without melting at ca. 300 8C [lit.23].
Melting points were measured with a Yanaco Mp 500
apparatus. 1H NMR spectra were recorded on a Bruker
DRX-300 MHz spectrometer with tetramethylsilane as the
internal standard.
3.3.7. p-Toluic acid. Oxidation of p-xylene catalyzed by
system B gave p-phthalic aid as a white solid, 51% yield, mp
180–181 8C [lit.24 181 8C].
3.2. General procedure
3.3.8. 4-Chloro-2-fluorobenzoic acid. White solid, mp
207–210 8C (C2H5OH/H2O); dH (300 MHz, CD3COCD3)
7.9–8.0 (1H, m, ArH), 7.4–7.6 (2H, m, ArH).
Substituted toluene, catalysts, radical initiator, and halo-
benzene were added to a three-necked flask with a reflux
condenser. The mixture was heated, with oxygen bubbling
through the solution for 3–10 h. After the reaction was
finished, the mixture was cooled to room temperature, and
crystals precipitated. Then crude product was obtained by
filtration and further purified by recrystallization with
ethanol/water. The yields of acids were 32–96%.
3.3.9. 4-Bromo-2-fluorobenzoic acid. White solid, mp
237–240 8C (C2H5OH/H2O); dH (300 MHz, CD3COCD3)
8.0–8.1 (1H, m, ArH), 7.6–7.8 (2H, m, ArH).
3.3. Typical procedure
Acknowledgements
3.3.1. Typical procedure for the oxidation of p-bromo-
toluene in catalyst system A. p-Bromotoluene (2.56 g,
15 mmol), AIBN (0.098 g, 0.6 mmol), Co(C18H35O2)2
(0.557 g, 0.9 mmol), and dichlorobenzene (20 mL) were
added to a three-necked flask with a reflux condenser, and
the mixture was heated at 150 8C, then oxygen was bubbled
through the solution for 9 h. After the reaction was finished,
the mixture was cooled to room temperature and p-
bromobenzoic acid was precipitated. The crude product
(2.71 g) was purified by recrystallization with ethanol/
water, mp 251–252 8C [lit.17 251–253 8C]. The yield was
92%.
This project was supported by the National Natural Science
Foundation of China (No. 20172016), Shanghai Phosphor
Project of Science and Technology for Excellent Young
Research (No. 01QA14017), the Foundation of Shanghai
Science and Technology Development, and the China
Petroleum and Chemical Corporation (No. 4502013).
References and notes
1. Sheldon, R. A.; Kochi, J. K.; et al. Metal-catalyzed oxidations
of organic compounds; Academic: New York, 1981.
2. Hudlicky, M. Oxidation in organic chemistry. ACS Mono-
graph 186; American Chemical Society: Washington, DC,
1990.
3.3.2. Typical procedure for the oxidation of p-methoxy-
toluene in catalyst system B. p-Methoxytoluene (2 g,
16.4 mmol), AIBN (0.081 g, 0.4 mmol), Co(OAc)2·4H2O
(0.204 g, 0.8 mmol), NaBr (0.056 g, 0.54 mmol), HOAc
(0.49 g, 8.2 mmol) and dichlorobenzene (10 mL) were
added to a three-necked flask fitted with a reflux condenser.
The mixture was heated to 110 8C with oxygen bubbling
3. Trost, B. M. Comprehensive organic synthesis (oxidation);
Pergamon: New York, 1991.
4. Sato, K.; Aoki, M.; Tagaki, J.; Noyori, R. J. Am. Chem. Soc.
1997, 119, 12386–12387.