ZnO: A versatile agent for benzylic oxidations

Article abstract of DOI:10.1016/j.tetlet.2005.05.104

Zinc oxide catalyzed oxidation of various alkylbenzenes, naphthalene and 1,2,3,4-tetrahydronaphthalene in air using microwave irradiation or conventional heating in the presence of N,N-dimethylformamide is described.

Full text of DOI:10.1016/j.tetlet.2005.05.104

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4957–4960
ZnO: a versatile agent for benzylic oxidations
a
Monika Gupta, Satya Paul, Rajive Gupta and Andr e´ Loupy
a,
a
b,
*
a
Department of Chemistry, University of Jammu, Jammu 180 006, India
Laboratoire des R e´ actions S e´ lectives sur Supports, CNRS UMR 8615, ICMMO, Universit e´ Paris-Sud, 91405 Orsay Cedex, France
b
Received 11 January 2005; revised 23 May 2005; accepted 24 May 2005
Available online 13 June 2005
Abstract—Zinc oxide catalyzed oxidation of various alkylbenzenes, naphthalene and 1,2,3,4-tetrahydronaphthalene in air using
microwave irradiation or conventional heating in the presence of N,N-dimethylformamide is described.
Ó 2005 Elsevier Ltd. All rights reserved.
1
. Introduction
with other metal oxides. For instance, zinc oxide in com-
bination with CuO and alumina has been employed for
the catalytic oxidation of phenols, t-BuOH and methyl-
Oxidation is a fundamental transformation in organic
1
–4
15
synthesis. Benzylic oxidation holds a unique place be-
cause of its application in industry and academia. Lab-
oratory scale liquid-phase benzylic oxidations are
generally carried out with a large excess of chromium
or manganese reagents. The metal residues are environ-
mentally undesirable and often cause problems during
work-up. Recently, nickel-catalyzed benzylic oxidation
of toluenes was reported. Other reagents, which have
been used include ceric ammonium nitrate in aqueous
acetic acid or in HClO , potassium bromate, chro-
4
vinyl ketone; a mixture of CuO, ZnO and TiO has
2
been concerned as catalyst for the hydrogenation of cyc-
1
6
lic aliphatic esters and alcohols; ZnO in combination
with CuO has been involved in the preparation of N-
3
17
cyclohexylaniline from aniline and cyclohexanol;
ZnO in combination with Cu and Cr O has served
2
3
1
8
for methanol synthesis; Fe–ZnO catalyst was used
for the oxidative dehydrogenation of n-butane to bu-
tene; a mixture of ZnO, CuCl , CaCO and MgCO
2 3 3
5
1
9
6
7
was advocated as an additive for preventing clinker for-
20
8
9
mium trioxide in acetic anhydride, selenium dioxide,
1
mation during coal combustion; copper zinc oxide cat-
alyst has been used for ambient temperature carbon
0
11
chromyl chloride, silver(II)oxide in phosphoric acid,
1
2
21
potassium permanganate adsorbed on alumina, and
,6-bis(triphenylphosphonium)cyclohexene peroxodisul-
monoxide oxidation; ZnO in combination with CaCO3
and SiO has been employed for preparing UV-resistant
22
plastic master batch.
3
2
13
fate. Many of these reagents are quite expensive and
suffer from harsh reaction conditions. Thus, there is a
need to develop procedures, which use inexpensive and
non-toxic oxidizing agents. Recently, we have reported
solvent-free benzylic oxidations using a urea–hydrogen
peroxide complex under microwave irradiation.
2
3
The coupling of microwave (MW) irradiation with the
use of catalysts or mineral-supported reagents provides
chemical processes with special attributes such as
enhanced reaction rates, higher yields, better selectivity
and improved ease of manipulation.
1
4
The most preferred of reagents would be those which are
easy to handle, inexpensive, non-toxic and easily re-
moved during work-up. Zinc oxide is a non-toxic, inex-
pensive and non-hygroscopic white powder. It has been
used for a number of organic syntheses in combination
Since ZnO is easily available and non-toxic, we wish to
report here some efficient ZnO mediated benzylic oxida-
tions under air under MW irradiation using small
amounts of DMF, or by conventional heating in an
oil-bath equipped with a thermostat using DMF as sol-
vent. To the best of our knowledge, ZnO has not yet
been reported as catalyst/mediator for benzylic oxida-
tions. This method provides a noticeable improvement
over other existing method as ZnO is not toxic or expen-
sive, work-up being simply reduced to filtration followed
Keywords: Alkylbenzenes; Zinc oxide; Benzylic oxidations; Microwave
irradiation; Oil-bath heating; Selectivity.
*
Corresponding author. Fax: +91 191 2505086; e-mail addresses:
paul7@rediffmail.com; aloupy@icmo.u-psud.fr
Fax: +33 1 69 1546 79.
0
040-4039/$ - see front matter Ó 2005Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.104

4958
M. Gupta et al. / Tetrahedron Letters 46 (2005) 4957–4960
by treatment with crushed ice. Furthermore, ZnO has
been shown to interact efficiently with MW radiation
to reach 326 °C within 5.5 min when submitted to MW
exposition in a commercial oven at a 1 kW emitted
Subsequently, this method was extended to various
substituted toluenes bearing electron-withdrawing or
electron-donating groups, providing the corresponding
benzoic acids in fairly good to excellent yields (Table 2).
2
4
power.
After establishing that benzylic oxidations were per-
formed successfully under MW irradiation, efforts were
made to conduct these reactions using conventional
heating in which DMF was chosen as solvent and the
reaction temperature kept at 90 °C. The best conditions
were obtained when toluene (10 mmol), ZnO (2.5mmol)
and DMF (5mL) were stirred in a pre-heated oil-bath at
90 °C, affording benzoic acid in 81% yield. This method
was extended to substituted toluenes, yielding the corre-
sponding benzoic acids in moderate to excellent yields.
Significant results for ZnO-mediated benzylic oxidations
under both MW irradiation or oil-bath heating are sum-
marized in Table 2. In general, yields obtained with MW
irradiation were significantly improved (10–18% points)
(entries 3, 5, 9–15) when compared to oil-bath experi-
ments conducted at 90 °C.
The experimental conditions for the oxidation of toluene
to benzoic acid were explored either in the absence of
solvent or in the presence of DMF or o-dichlorobenzene
(
DCB) under MW irradiation, since these solvents inter-
act strongly with microwaves due to their high polari-
ties. The oxidation efficiency of ZnO was determined
on the basis of the amount of ZnO and solvent used.
The results are summarized in Table 1.
In the absence of solvent, no reaction was observed
within 6 min while good results were obtained in the
presence of DMF. The work-up procedure is indeed
easy, requiring only treatment with crushed ice. In addi-
tion, there is no alteration in the yield from 0.25to
1 equiv of DMF except a slight decrease in the irradia-
tion period.
We then studied the use of ZnO for the selective oxida-
tions of one of the methyl groups in dimethylbenzene
simply by regulating the amount of ZnO and heating
conditions. As a typical example, in the case of 1,2-
dimethylbenzene (Table 2, entry 5), when 2.5 mmol of
ZnO was used, 2-methylbenzoic acid was obtained in
80% yield under MW exposure within 8 min and 65%
yield using oil-bath heating within 1.5h. However, if
the amount of ZnO was doubled, 1,2-dimethylbenzene
(Table 2, entry 6) gave phthalic acid in 89% yield using
microwaves for 5min and 7 5% yield using oil-bath heat-
ing for 2 h. Similarly, in the case of 1,4-dimethylbenzene
(Table 2, entries 7 and 8), 4-methylbenzoic acid and tere-
phthalic acid can be obtained selectively using either
MW irradiation or oil-bath heating.
ZnO intervention for benzylic oxidations proved neces-
sary, since no reaction occurred when the oxidation of
toluene was performed using either DMF or DCB in
the absence of ZnO under MW irradiation (Table 1, en-
tries 8 and 9) for up to 8 min. Furthermore, the necessity
of oxygen (air) was evaluated by carrying out the oxida-
tion of toluene (10 mmol) under nitrogen in the presence
of ZnO (2.5mmol) and DMF (5mL for oil-bath and
2
9
.5mmol for MW heating) by stirring in an oil-bath at
0 °C or irradiating in a MW oven. No reaction was ob-
served by TLC even after 5h in the case of oil-bath or
6
min in the case of MW heating, whereas an 83% yield
was obtained when 10 mmol of toluene was irradiated
under MW together with DMF (2.5mmol) and ZnO
(
2.5mmol) in open vessels.
In the case of toluenes containing an acetoxy group at
the 2-, 3- or 4-position (entries 11–13), the reaction pro-
ceeded selectively to give 2-, 3- or 4-acetoxybenzoic acids
and no phenol (hydrolysis product) was detected by
TLC. Furthermore, toluenes substituted at the 3- or 4-
position by electron-withdrawing groups such as a nitro
moiety were oxidized smoothly to the corresponding
benzoic acids in excellent yield (entries 3 and 4). Tolu-
enes substituted by electron rich groups (entries 5–8
and 11) also underwent the oxidation efficiently. In the
case of ethylbenzene, where there is a possibility of for-
mation of acetophenone, the reaction took place
exclusively to provide benzoic acid and no acetophenone
was detected by TLC. The present mild method was also
successful for the oxidation of naphthalene and tetralin
to phthalic acid, for which generally highly drastic con-
ditions are required.
Table 1. Conditions and results for the ZnO-mediated oxidation of
toluene to benzoic acid under MW irradiation
a
Entry
Experimental conditions
Isolated
c
yield (%)
Temperature
d
(°C)
b
Solvent mmol Time (min)
1
2
3
4
—
—
6
No reaction 72
DMF
DMF
DMF
2.56
83
82
95
100
5.0
10.0
45
4.5
4.2584
100
107
107
1
7
5
6
7
8
9
1
DCB
52 .5
DCB
DCB
DMF
DCB
DMF
5.0
10.0
7
6.2546
47
105
e
e
2.58
No reaction 90
No reaction 98
No reaction 96
2.58
2.56
f
0
a
The experiments were carried out by mixing toluene (10 mmol) and
ZnO (2.5mmol) with the solvent.
In order to check the possibility of specific non-thermal
MW effect for the ZnO-mediated oxidation of alkylbenz-
enes, we carried out the oxidation of toluene (Table 2,
entry 1) using a pre-heated oil-bath at 95 °C (tempera-
ture measured at the end of the reaction in the MW
oven) for 6 min keeping all other conditions identical
to the MW experiment. It was found that no reaction
b
c
Reaction time for which maximum yields were achieved.
Mean value of three experimental runs.
d
Temperature evaluated at the end of exposure during MW experi-
ment by immersing a glass thermometer into the reaction mixture
and was a approximate temperature range.
e
f
Experiment conducted without the presence of ZnO.
Experiment conducted under nitrogen atmosphere.

M. Gupta et al. / Tetrahedron Letters 46 (2005) 4957–4960
Table 2. Results of ZnO-mediated benzylic oxidations in an air atmosphere
CH3
4959
COOH
MW, ZnO, DMF
or
R
R
∆
, ZnO, DMF
b
a
a
Entry
Reactant
Product
MW
Oil-bath (90 °C)
c
Time (min)
d
Isolated yield (%)
d
Isolated yield (%)
Time (h)
2.581
1
2
3
4
Toluene
Ethylbenzene
Benzoic acid
Benzoic acid
6
83
7
853
76
82
81
3-Methyl-1-nitrobenzene
4-Methyl-1-nitrobenzene
3-Nitrobenzoic acid
4-Nitrobenzoic acid
3
2.1565
1.565
7
852
80
e,f
5
6
7
8
9
1
1
1
1
1
1
1,2-Dimethylbenzene
2-Methylbenzoic acid
8
589
g
1,2-Dimethylbenzene
1,4-Dimethylbenzene
1,4-Dimethylbenzene
2-Methylphenylamine
3-Methylphenol
Phthalic acid
4-Methylbenzoic acid
2
75
6
575 721.15
77
1
73
e
Terephthalic acid
3-Aminobenzoic acid
585
5.5
9
7
76
0
1
2
3
4
3-Hydroxybenzoic acid
2-Acetyloxybenzoic acid
3-Acetyloxybenzoic acid
4-Acetyloxybenzoic acid
Phthalic acid
85
80
4
6
73
70
2-Methylphenyl acetate
3-Methylphenyl acetate
4-Methylphenyl acetate
Naphthalene
6
851
83
67
8
2
72
7.578
82
63 5. 15
3.5 67
51,2,3,4-Tetrahydronaphthalene
Phthalic acid
15
a
The experiments were carried out by mixing appropriate alkylbenzene (10 mmol), ZnO (2.5mmol) and DMF (2.5mmol for MW experiment and
mL for oil-bath experiment).
5
b
c
d
e
f
1
All products were characterized by H NMR, IR, MS and by comparison with authentic samples.
Microwave irradiation was carried out with pulses of 15s followed by a 5s cooling periods.
Mean value of the isolated yield for three experimental runs.
For entries 6 and 8, the amount of catalyst used was 5mmol while all other conditions remain as described in Experimental section.
1
In case of entry 5, the H NMR of crude product obtained after work-up by MW heating approach showed the presence of 2-methylbenzoic acid
(88%), phthalic acid (5%) and the rest may be starting materials.
1
g
In case of entry 6, the H NMR of crude product obtained after work-up by MW heating approach showed the presence of phthalic acid (95%) and
no 2-methylbenzoic acid was detected.
took place (TLC), although a yield of 78% was obtained
when reaction time was extended to 3.25h. This obser-
vation suggests that the effect of MW irradiation is not
purely thermal.
tions using inexpensive and non-toxic zinc oxide under
MW irradiation or oil-bath heating. This method may
be a good alternative to well-known methods, since
the oxidation proceeds expeditiously in high yields.
The selectivity can be achieved by regulating the amount
of ZnO and the reaction time under MW exposure or
oil-bath heating. However, the benefit of the MW meth-
od is double, as only a small amount of DMF is required
as an additive (25mol % vs ZnO), and reaction times are
far shorter and often lead to better or at least equivalent
yields.
Furthermore, the importance of our method lies in the
fact that ZnO can be re-used after simple washing with
distilled water and diethyl ether. The results of re-use
studies are given in Table 3.
In conclusion, a rapid, economic and environmentally
friendly method has been developed for benzylic oxida-
2. General procedure for the ZnO-mediated oxidation of
alkylbenzenes
Table 3. Results of re-use studies of ZnO for the oxidation of toluene
to benzoic acid
a
a
No. of uses
MW
Oil-bath heating
2.1. Microwave (MW) experiment
b
c
Yield (%) Time (h)
b
c
Time (min)
Yield (%)
Alkylbenzene (10 mmol), zinc oxide (0.115g, 2.5mmol)
and N,N-dimethylformamide (0.18 mL, 2.5mmol) were
placed in a borosil beaker (50 mL). The mixture was
mixed properly with the help of a glass rod (15s) and
then irradiated under safe conditions in a domestic
microwave oven at 800 W (LG CHEF MS 192 operating
at 2450 MHz providing a maximum output of 800 W)
for the reaction times given in Table 2. The reaction
mixture was cooled to room temperature and diluted
with DMF (5mL). It was filtered and ice-cold water
(100 mL) was added to the filtrate. The solution was ex-
1
2
3
4
6
83
82
2.581
2.7580
7
8.580
9.1576
71
37 . 41 5
4
70
5
11
6 44 .5
a
The experiments were carried out by mixing appropriate toluene
10 mmol), ZnO (2.5mmol) and DMF (2.5mmol for MW experi-
(
ment and 5mL for oil-bath experiment). The mixture was irradiated
with MW for the indicated period (6–11 min) or stirred in an oil-bath
at 90 °C for the indicated period (2.5–4.5 h).
b
c
The reaction time where maximum yields were achieved.
Mean value of three experimental runs.
tracted with CHCl and the solvent was removed under
3

4960
M. Gupta et al. / Tetrahedron Letters 46 (2005) 4957–4960
reduced pressure after drying over anhydrous sodium
sulfate. Finally, the products were purified either by
crystallization from CHCl –pet. ether or by column
7. Ganin, E.; Amer, I. Synth. Commun. 1995, 25, 3149.
8
9
. Nishimura, T. Org. Synth. 1956, 36, 5 8.
. Kaplan, H. J. Am. Chem. Soc. 1941, 63, 2654.
3
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1
0. Richter, V. V. Chem. Ber. 1886, 19, 1060.
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chromatography on silica gel using pet. ether as eluant
(
Table 2). The structures of the products were confirmed
1
12. Zhao, D.; Lee, D. G. Synthesis 1994, 915.
1
by H NMR, IR, MS and by comparison with authentic
samples available commercially or prepared according
to the literature methods.
3. Badri, R.; Soleymani, M. Synth. Commun. 2002, 32,
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1
4. Paul, S.; Nanda, P.; Gupta, R. Synlett 2004, 531.
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2
.2. Oil-bath experiment
1
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4
,929,777, 1990; Chem. Abstr. 1990, 113, 114662z.
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a round-bottomed flask (25mL) equipped with a reflux
condenser. The reaction mixture was stirred in a pre-
heated oil-bath at 90 °C for the reaction times as given
in Table 2. The products were obtained after the same
work-up procedure as for the MW-assisted method.
1
7. Romanovskaya, L. G.; Belov, V. V.; Sula, L. I.; Perkova,
V. N.; Yureva, T. M.; Prudnikova, O. Y.; Minyukova, T.
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