Green oxidation of methylarenes to benzoic acids with bromide/bromate in water

Article abstract of DOI:10.1080/00397910903340678

An efficient and convenient procedure has been developed for the oxidation of methylarenes to the corresponding benzoic acids using a bromide/bromate-based reagent system in water. Regeneration and reusability of the bromide/bromate reagent is demonstrated.

Full text of DOI:10.1080/00397910903340678

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Green Oxidation of Methylarenes to
Benzoic Acids with Bromide/Bromate in
Water
a
a
b
Rajendra D. Patil , Sukalyan Bhadra , Subbarayappa Adimurthy
b
&
a
Brindaban C. Ranu
Central Salt and Marine Chemicals Research Institute, Council of
Scientific and Industrial Research, G. B. Marg, Bhavnagar, Gujarat,
India
b
Department of Organic Chemistry, Indian Association for the
Cultivation of Science, Jadavpur, Kolkata, India
Available online: 25 Aug 2010
To cite this article: Rajendra D. Patil, Sukalyan Bhadra, Subbarayappa Adimurthy & Brindaban C.
Ranu (2010): Green Oxidation of Methylarenes to Benzoic Acids with Bromide/Bromate in Water,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 40:19, 2922-2929
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1
Synthetic Communications , 40: 2922–2929, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903340678
GREEN OXIDATION OF METHYLARENES TO BENZOIC
ACIDS WITH BROMIDE/BROMATE IN WATER
1
Rajendra D. Patil, Sukalyan Bhadra,
2
1
Subbarayappa Adimurthy, and Brindaban C. Ranu
2
1
Central Salt and Marine Chemicals Research Institute, Council of Scientific
and Industrial Research, G. B. Marg, Bhavnagar, Gujarat, India
2
Department of Organic Chemistry, Indian Association for the Cultivation of
Science, Jadavpur, Kolkata, India
An efficient and convenient procedure has been developed for the oxidation of methylarenes
to the corresponding benzoic acids using a bromide/bromate-based reagent system in water.
Regeneration and reusability of the bromide/bromate reagent is demonstrated.
Keywords: Benzoic acids; bromide=bromate; methylarenes; oxidation
INTRODUCTION
The oxidation of methyl aromatics into the corresponding benzoic acids is an
important transformation in organic synthesis as these carbonyl derivatives constitute
[
1]
versatile building blocks in pharmaceutical and polymer industries. A variety of
oxidizing agents such as KMnO , CrO , Na Cr O , TiO , NaIO , and HNO are
4
3
2
2
7
2
4
3
[2–6]
available to effect this key reaction.
However, these metallic reagents are often
required in stoichiometric amounts, and these procedures are associated with
environmental pollution because of the large amounts of hazardous metallic wastes.
Moreover, purification of the reaction products is often very tedious because of the
difficulty in separation of the metal residues from the product. Despite the industrial
importance of this process and ever-growing environmental concerns, efficient
[7]
catalytic systems have been rarely described. Recently, WO =70% tert-butyl hydroper-
3
[8]
oxide (TBHP)=aqueous NaOH has been reported. Although several methods are
known for the synthesis of aromatic carboxylic acids, preparation under mild conditions
without use of heavy-metal catalysts and generation of waste is an ultimate goal in view
of technical, economical, and industrial aspects. As a part of our continuing activities to
[9]
develop green procedures that avoid hazardous reagents, we report herein a novel,
heavy-metal-free, and recyclable reagent system for the oxidation of methylarenes to
Received July 10, 2009.
Address correspondence to Subbarayappa Adimurthy, Central Salt and Marine Chemicals
Research Institute, Council of Scientific and Industrial Research, G. B. Marg, Bhavnagar 364 002,
Gujarat, India. E-mail: sadimurthy@yahoo.com
2
922

OXIDATION OF METHYLARENES
2923
Scheme 1. Oxidation of methyl arenes to benzoic acids.
their corresponding benzoic acids using a bromide=bromate reagent under mild con-
ditions in an open atmosphere with water as solvent (Scheme 1).
RESULTS AND DISCUSSION
To gain more insight into this process, the oxidation of methylarenes with
bromide=bromate under an aqueous acidic medium was investigated. In our earlier
studies, we showed that the reactions of bromide=bromate and acid in a 2:1:3 molar
[
9]
ratio [Eq. (1)] generates the reactive species BrOH. We think that this species is also
responsible for the oxidation of methylarenes.
ꢀ
ꢀ
þ
2
Br þ BrO þ 3 H ! 3BrOH
ð1Þ
3
A study for the oxidation of toluene by this reagent in different organic solvents such
as CH Cl , ClCH CH Cl, CCl , and CH OH demonstrated that the best result with
2
2
2
2
4
3
regard to the formation of carboxylic acid was achieved using water as solvent. To
optimize the reaction parameters, such as the amount of reagent system and reaction
temperature, the reaction of toluene was investigated under various conditions as
illustrated in Table 1. The best yield was obtained using 3 equivalents of bromide=
bromate=acid in a 2:1:3 molar ratio (Table 1, entry 3).
The present transformation, 1 to 2, proceeds through the intermediates of
benzyl alcohol 4 and aldehyde 3 [Eqs. (2)–(4)]. Thus, this transformation needs 3
equivalents of the reagent [Eq. (5)].
ArCH3 þ BrOH ! ArCH2OH þ HBr
ð2Þ
ð3Þ
ð4Þ
ð5Þ
ArCH OH þ BrOH ! ArCHO þ HBr þ H O
2
2
ArCHO þ BrOH ! ArCO2H þ HBr
ArCH þ 3BrOH ! ArCO H þ 3HBr þ H O
3
2
2
It clearly indicates that the intermediates 3 and 4 could be avoided completely by
using 3 equivalents of the reagent, and the desired product 2 was obtained in 72%
isolated yield (Table 1, entry 3). When the reaction was conducted at room tempera-
ture, it took a prolonged period of time to consume the total reagent and undesired
products were formed (Table 1, entry 4). This indicates that the selective activation
of aromatic alkyl C-H group at room temperature will be difficult without any metal
[
4,10]
catalyst.
It is further observed that in the absence of visible light, nuclear

2924
R. D. PATIL ET AL.
ꢀ
ꢀ
þ
Table 1. Oxidation of toluene (1) with Br =BrO =H reagent under different conditions
3
a
Run
Reagent (eqv.)
Conv (%)
2
3
4
5
Others
1
2
3
1.0
2.0
3.0
3.0
3.0
100
100
100
100
100
22.6
41.1
10.7
7.3
—
25.4
22.4
—
10.2
9.6
Rest
Rest
Rest
b
90 (72)
9.0
32.6
4.6
c
d
4
4.4
—
—
—
26.4
58.6
59.4
Rest
e
5
ꢀ
ꢀ
þ
ꢁ
Notes. Conditions: 10.86 mmol of 1, Br =BrO =H are in a 2:1:3 molar ratio, water, 100 C, 8.00 h, in
visible light. Product distribution is based on GC area percentages.
3
a
GC-MS.
Isolated yield.
Reaction carried out at rt for 16 h.
b
c
d
Constituted with multinuclear brominated and oxidized products not mentioned in the table.
Without visible light.
e
brominated products were formed (Table 1, entry 5). Presumably, the presence of
visible light is necessary to initiate the reaction if it proceeds via a free-radical mech-
[
11]
anism.
To check whether the present transformation proceeds via the benzylic
[6e]
bromide mechanism, we performed the reaction of toluene under the same con-
ditions in dichloromethane and water. In the former case, benzylic brominated pro-
ducts 6 and 7 were formed, and in the latter case, the desired product benzoic acid 2
(Scheme 2) was produced. Thus, the transformation of toluene to benzoic acid is
facilitated in water rather than in organic solvents. Based on all these observations,
ꢁ
the oxidations were carried out in water at 100 C using 3 equivalents of reagent sys-
tem. The isolation of the product is very simple. The completion of the reaction is
indicated by the disappearance of the color of the reactive species BrOH=Br . The
2
reaction mixture was allowed to cool to room temperature, and the solid was filtered.
The solid was washed with cold water and dried to get the product.
Several substituted methylarenes were subjected to oxidation by this procedure
to provide the corresponding benzoic acids in good yields. The results are summar-
ized in Table 2. The position of substitution (o, m, p) does not affect the oxidation
process. The hindered o-substituted toluenes (Table 2, entries 8 and 13) were also
2 2 2
Scheme 2. Effect of H O and CH Cl on oxidation of toluene.

OXIDATION OF METHYLARENES
2925
Table 2. Oxidation of alkylarenes to the corresponding benzoic acids
a
ꢁ
Entry
1
Substrate
Time (h)
Product
Yield (%)
Mp (Lit. mp) ( C)
Ref.
12
8
72
122 (121–125)
2
3
4
5
9
7
84
69
82
236 (237–240)
137 (139–141)
167 (163–165)
12
12
13
5
6
8
5
83
75
212 (208–209)
238 (238–241)
14
12
7
8
6
6
70
73
155 (153–157)
142 (138–140)
12
12
9
10
73
180 (182–184)
12
1
1
1
1
0
1
2
3
7
8
70
66
67
63
160 (155–158)
189 (185–187)
268 (270–273)
164 (160–162)
12
12
12
12
9
10
(
Continued )

2926
R. D. PATIL ET AL.
Table 2. Continued
a
ꢁ
Entry
Substrate
Time (h)
9
Product
Yield (%)
Mp (Lit. mp) ( C)
Ref.
12
1
1
4
5
71
64
155 (157–160)
122 (121–125)
10
12
a
1
13
Isolated yields of pure products ( H and C NMR).
oxidized without any difficulty. In general, the deactivated methylarenes were more
facile in this oxidation process. The highly deactivated toluenes such as nitrotoluenes
[6a]
were not always easy to oxidize.
The unactivated arenes such as a-methyl naph-
thalene (Table 2, entry 14) and ethyl benzene (Table 2, entry 15) also produced
the corresponding carboxylic acids. However, oxidations of highly activating methy-
larenes were not encouraged, being associated with considerable amounts of ring
brominated products.
Because bromide is not consumed as such in the oxidation process, both the
bromide=bromate ions ended up in the aqueous effluent as total bromide ions, and
we reoxidized a part of the bromide ion with NaOCl to bromate to regenerate the
reagent to its original form [Eq. (6)] under ambient conditions (Scheme 3). Sodium
chloride produced in the course of regeneration caused no problem in the oxidation
reactions. The regenerated reagent was successively used for oxidation of methylar-
enes under similar conditions. For a representative example, 4-nitrotoluene was
subjected to oxidation by this regenerated reagent system with three consecutive
cycles, and the results (Table 3) are same as with the fresh reagent.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
Br þ 3 OCl ! 2Br þ BrO þ 3Cl
ð6Þ
3
In conclusion, we have developed a very simple and efficient procedure for the
oxidation of methylarenes to the corresponding benzoic acids using an inexpensive
Scheme 3. Regeneration of bromide=bromate.

OXIDATION OF METHYLARENES
2927
Table 3. Oxidation of p-nitrotoluene with regenerated reagent
a
Cycle
Time (h)
Yield (%)
1
2
3
5.0
7.0
7.0
84
76
72
a
Isolated yield.
and easily available bromide=bromate reagent system. The most significant and
green feature of this methodology is the simple operation in water and use of no haz-
ardous organic solvent or toxic reagent in the entire process. The recyclability of the
reagent also adds to its green merit. Thus, this cost-effective and environmentally
friendly procedure is a practical alternative to the existing ones and will find useful
applications in academia as well as industry.
EXPERIMENTAL
General Experimental Procedure for the Oxidation of Methylarenes
to Benzoic Acids: Representative Procedure for 4-Nitrobenzoic Acid
(Table 2, Entry 2)
An aqueous solution of NaBr (3.00 g, 29.1 mmol) and H SO (2.14 g,
2
4
ꢁ
2
(
1.8 mmol) was added at 100 C (oil bath) to a stirred solution of 4-nitrotoluene
2.0 g, 14.5 mmol), water (20 ml), and NaBrO (2.20 g, 14.5 mmol) during a per-
3
iod of 3 h in the presence of visible light. Stirring was continued for 2 h until the
brown color disappeared at the same temperature. The reaction mixture was
ꢁ
allowed to attain room temperature (25 C). The solid separated was filtered
off, washed with water, and dried to afford 4-nitrobenzoic acid (2.03 g, 84%).
Recrystallization from hot water provided the analytically pure sample. The
1
spectroscopic data [infrared (IR), H NMR, and C NMR)] are in good agree-
13
[
6e]
ment with the reported values.
The aqueous part left after workup of the first
cycle was neutralized and thereafter treated with NaOCl solution (81.5 ml of 4%
-
ꢀ
3
available chlorine) to oxidize 1=3 of total Br into BrO and to regenerate the
ꢀ
ꢀ
original 2:1 Br =BrO3 couple. Fresh 4-nitrotoluene (2.0 g, 14.5 mmol) was added
ꢁ
to it, followed by H SO (2.14 g, 21.8 mmol) at 100 C (oil bath) during a period
2
4
of 3 h, and stirring was continued for 4 h. After workup (as mentioned pre-
viously), pure 4-nitrobenzoic acid was obtained (1.84 g, 76%). A similar pro-
cedure was followed for the third cycle. All of the products are known
compounds and were easily identified by comparison of their spectroscopic data
[
12]
with the reported values.

2928
R. D. PATIL ET AL.
ACKNOWLEDGMENT
The authors gratefully acknowledge the Department of Science and
Technology, New Delhi, India, for financial support of this project under the Green
Chemistry Task Force Scheme [No. SR=S5=GC-02A=2006].
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