Efficient method for the oxidation of aldehydes and diols with tert-butylhydroperoxide under transition metal-free conditions

Article abstract of DOI:10.1016/j.tet.2013.07.101

An efficient, mild, and simple protocol is presented for the oxidation of aldehydes and diols to carboxylic acids utilizing 70% aq TBHP as oxidant and t-BuOK as additive. The oxidation of aldehydes could be achieved by two methods under aqueous medium. Excellent yields of products were obtained in short reaction times. Notably, the products were isolated by simple filtration technique and do not involve chromatographic separation. These reactions may prove to be valuable alternatives to traditional metal-mediated oxidations. Oxidation does not require any transition metals or organic solvents in reaction, making this protocol green.

Full text of DOI:10.1016/j.tet.2013.07.101

Tetrahedron 69 (2013) 8929e8935
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient method for the oxidation of aldehydes and diols with tert-
butylhydroperoxide under transition metal-free conditions
Tanveer Mahammadali Shaikh b, Fung-E Hong a
a
,
,
*
a
Department of Chemistry, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung, Taiwan, ROC
Department of Chemistry, Vel. Tech. University, Avadi, Chennai, T.N., India
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 May 2013
Received in revised form 16 July 2013
Accepted 25 July 2013
Available online 13 August 2013
An efficient, mild, and simple protocol is presented for the oxidation of aldehydes and diols to carboxylic
acids utilizing 70% aq TBHP as oxidant and t-BuOK as additive. The oxidation of aldehydes could be
achieved by two methods under aqueous medium. Excellent yields of products were obtained in short
reaction times. Notably, the products were isolated by simple filtration technique and do not involve
chromatographic separation. These reactions may prove to be valuable alternatives to traditional metal-
mediated oxidations. Oxidation does not require any transition metals or organic solvents in reaction,
making this protocol green.
Keywords:
Oxidation
Aldehydes
Diols
Ó 2013 Elsevier Ltd. All rights reserved.
Carboxylic acids
Aq TBHP
1. Introduction
oxidant KMnO
4
/NaH
2
PO
4
.19 The combination of metal catalyst
with stoichiometric oxidants TBHP or
2
0
21
22
CuCl, AgNO
3
,
Bi
2
O
3
,
Carboxylic acids are ubiquitous and important key functional
groups that are present in natural products, agricultural and bio-
active molecules, pharmaceuticals and polymers. Thus, synthesis of
carboxylic acids by oxidation of a variety of substrates is one of the
fundamental transformations in organic synthesis, which has ex-
2 2
H O were also described in literature. Despite considerable prog-
ress in such transformations, the search for new and more efficient
methods is still under actively pursuing that involves implication of
cheap and eco-friendly reagents.
Modern organic synthesis requires using oxidants, which are
highly selective, efficient, and environmental friendly. Aqueous
1
tensively used both in academia and industry. As a result a variety
2
3
of oxidizing methods to the direct oxidations of aldehydes or diols
to carboxylic acids or carbonyl compounds had been developed,
which led to the discovery of several new oxidizing various re-
tertiary-butyl hydroperoxide (TBHP) is an effective oxidant, for
numerous transformations and its utility has also grown rapidly.
This is due in part to TBHP’s stability, non-toxic nature, non-
polluting by products, and cost effectiveness. Also, environmen-
tally friendly oxidizing agents allow to get rid of harmful com-
pounds in manufacturing processes. Herein, we report efficient
transition metal-free, operationally convenient protocols for the
direct oxidation of aldehydes and diols to the corresponding car-
boxylic acids in aqueous medium using combination of aq 70%
TBHP/potassium tert-butoxide (t-BuOK) (Scheme 1).
2
agents. Conventionally, oxidation of aldehydes to carboxylic acids
3 2 4
has been achieved employing Jones reagent (CrO /H SO /acetone)
or manganese salts.3 However, Mn- and Cr-based side products
4
may be considered as a potentially environmental hazard. More-
5
6
7
over, metal-free reagents, oxone, porphyrin sensitizer, NHC,
biomimetic-flavin,8 are reported in literature to accomplish this
transformation. Several attempts had been made by different
groups finding alternatives to such oxidation procedures. For ex-
9
ample, metal-mediated oxidations were reported employing Ca,
1
0
11
12
13
14
15
16
17
18
Ni, Se, Mg, W, Co, Pd, V, Mo, and Au. Sedelmeier,
Ley, and Baumann together disclosed to achieve oxidation of al-
dehydes to carboxylic acids employing stoichiometric amount of
*
Corresponding author. E-mail address: fehong@dragon.nchu.edu.tw (F.-E. Hong).
Scheme 1.
0
040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.101

8930
T.M. Shaikh, F.-E. Hong / Tetrahedron 69 (2013) 8929e8935
ꢀ
2
2
. Results and discussion
aldehyde 1a, to the oxidation reaction at 25 C and monitored very
carefully. Surprisingly, the 4-bromobenzoic acid was excellently
obtained in 90% within 40 h (entry 15). These results lead to the
assumption that the oxidation of aldehydes (1), to the corre-
.1. Oxidation of aldehydes
According to the literature reports, several methodologies have
sponding carboxylic acid (2), could be achieved by two methods (i)
ꢀ
been utilized TBHP as oxidant in combination with metal-cata-
Method-A: aq 70% TBHP, t-BuOK, H
2
O, 60 C, 5 h (ii) Method-B: aq
2
0e22
ꢀ
lyzed
oxidation of aldehydes to carboxylic acids. Amongst
70% TBHP, t-BuOK, H
2
O, 25 C, 40 h.
them the usage of transition metals, such as copper, silver, and
With the optimized oxidation conditions in hand, the sub-
2
0e22
bismuth have been recently reported.
Therefore, it is impor-
strate scope with various aromatic and aliphatic aldehydes using
ꢀ
tant and useful to develop new metal-free methods to oxidize al-
dehydes to carboxylic acids by user-friendly protocols.
method-A [aq 70% TBHP, t-BuOK, H
2
O, 60 C, 5 h] was in-
vestigated. These results are presented in Table 2. All the alde-
hydes were selectively and smoothly converted to the
corresponding carboxylic acids as sole product in excellent
yields without any evidence for the formation of Dakin (phe-
We chose to focus our initial attention on determining whether
aq 70% TBHP alone promoted oxidation of aldehydes. In preliminary
studies, we used stable, 4-bromobenzaldehyde (1a) for the oxida-
tion reaction in aqueous medium and the results are presented in
Table 1. When 4-bromobenzaldehyde was reacted with stoichio-
2
4a
24b
nols)
and other over-oxidized products.
The oxidation of
benzaldehyde (2b) proceeds smoothly under the standard re-
action conditions to give the benzoic acid in 94% following acidic
work-up (Table 1, entry 1). Aldehydes having para-, meta- and
ortho-substituted halides afforded the corresponding carboxylic
acids 2a, 2c, 2d, and 2d in excellent yields (92, 93, 90, and 90%,
respectively, entries 2e5, Table 2). Both electron-rich and
electron-deficient aldehydes were smoothly oxidized to the
metric amount of aq 70% TBHP and 0.5 equiv t-BuOK in water at
ꢀ
2
5 C, the corresponding 4-bromobenzoic acid (2a) was obtained in
1
0% yield (Table 1, entry 1). Under similar reaction conditions, 2a
ꢀ
was obtained in 45% yield at 60 C (entry 1). While variation in
concentration of base and temperature provided the oxidized
product upto 32% yields (entries 2e3). When we increased the
oxidant aq 70% TBHP to 2 equiv, the reaction produced a 40% iso-
lated yield of 4-bromobenzoic acid and unreacted 4-
bromobenzaldehyde was recovered (entry 4). Interestingly, the
combination of aq 70% TBHP and NaOH gave competently conver-
sions within short reaction time of 5 h (entries 5e6). To evaluate
the effect of additives, the blank oxidation was carried out with aq
Table 2
a
Oxidation of aldehydes to carboxylic acids
Entry
1
Aldehyde
Productb
Yield (%)c
7
0% TBHP alone under similar reaction conditions without
94, 96d
employing NaOH. However, the oxidation was found to be very
slow and gave very poor yield of the oxidized product (entry 7).
Changing the source of base from NaOH to K
dine, and triethylamine did not showed any improvement in oxi-
dation reaction. Replacement of aq 70% TBHP by other oxidants,
3
PO
4
, NaHCO
3
, pyri-
92, 90d
2
2
such as, NMO, TEMPO, and O were ineffective or resulted in low
3
4
93
90
yield of carboxylic acids (entries 10e12). Furthermore, the oxida-
tion of 1a, in the presence of aq 70% TBHP and KOH resulted in the
formation of carboxylic acid 2a, in 89% yields (entry 13). Good re-
sults were obtained employing t-BuOK produced 2a, in excellent
yield of 92% (entry 14). Additionally, we were interested to perform
this oxidation process at room temperature. Thus, we subjected
5
90
Table 1
a
Optimization of oxidation of aldehydes
6
7
88
85
ꢀ
Entry
Oxidant (equiv)
Additive (equiv)
Temp
C
Time h
Yield (%)
1
2
3
4
5
6
7
8
9
TBHP (1)
TBHP (1)
TBHP (1)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
NMO (2)
TEMPO (1)
K
K
K
K
2
2
2
2
CO
CO
CO
CO
3
3
3
3
(0.5)
(1)
(1)
25
25
50
50
50
60
60
60
60
60
60
60
60
60
25
15
12
12
8
8
5
20
5
5
5
5
10(45)b
20
32
40
72
86
Trace
42
Trace
nr
nr
(1)
8
93
NaOH (1)
NaOH (1)
None
3 4
K PO (1)
Pyridine (1)
NaOH (1)
NaOH (1)
NaOH (1)
KOH (1)
9
95
96
10
11
12
13
14
15
O
2
5
5
5
40
nr
89
92 (93%)
90
TBHP (2)
TBHP (2)
TBHP (2)
10
c
t-BuOK (1)
t-BuOK (1)
a
Reaction conditions: aldehyde (0.5 mmol), oxidant, additive, water; acidic work-
11
82
up.
b
ꢀ
Reaction was carried out 60 C.
c
The reaction was conducted in acetonitrile.

T.M. Shaikh, F.-E. Hong / Tetrahedron 69 (2013) 8929e8935
8931
Table 2 (continued )
diols, we subjected 1-phenylethane-1,2-diol (3a), which contains
Productb
Yield (%)c
both primary and secondary alcohol functionality. Surprisingly,
diol 3a underwent oxidation with TBHP at 60 C to furnish
Entry
Aldehyde
ꢀ
benzoic acid (2a) in 43% yield and unreacted diol 3a was re-
covered from the reaction mixture. Furthermore, we thought to
explore this oxidation method to convert diols directly to the
corresponding carboxylic acids employing aq 70% TBHP and t-
BuOK (Scheme 2).
1
1
2
3
95e
92e
14
70
1
1
5
6
87
83
Scheme 2.
During recent decades, tremendous efforts have been made to
the oxidative cleavage of diols to carboxylic acids. Many metal
catalysts in combination with oxidants have been developed, such
1
7
79
2
5
26
27
28
as those involving MoO
2
(acac)
2
,
Pb(OAc)
Other non-metal oxidants, for exam-
2
O under high pressure, photoirradiation con-
4
,
Co(II), Ru-salts,
2
9
30
31
a
W-oxides,
V
2
O
5
,
2
NiCl .
Reaction conditions (Method-A): aldehyde (0.5 mmol), aq 70% TBHP (1 mmol), t-
3
2
ꢀ
ple, PhI(OAc)
2
,
BuOK (0.5 mmol), H
2
O, 60 C, 5 h; acidic work-up.
b
1
13
33a
33b
Products were characterized by mp H, C NMR.
Isolated yield of product.
Reaction conditions (Method-B): aldehyde (0.5 mmol), aq 70% TBHP (1 mmol), t-
ditions,
and NaOCl/NaClO
2
have been developed. However,
c
such reactions are often performed using organic solvents, which
often led to the formation of aldehydes as side products along with
desired carboxylic acids. Thus, required chromatographic purifica-
tion method to separate such products; which directly affects to use
in large scale synthesis.
d
ꢀ
BuOK (0.5 mmol), H
2
O, 25 C, 40 h; acidic work-up.
e
ꢀ
Reaction was stirred for 10 h at 60 C.
corresponding carboxylic acids. For example, oxidation of 4-
methoxy- or 3-methoxy-benzaldehydes resulted in the forma-
tion of 4-methoxy-(2f) or 3-methoxy-benzoic acids (2g) in 88%
and 85% yields, respectively (entries 6 & 7). The same oxidation
Table 3 describes optimization of reaction conditions to the di-
rect oxidation of diol (3a) to the corresponding carboxylic acid (2b).
For initial studies, 1-phenylethane-1,2-diol (3a) was chosen as the
candidate of substrate. Then, the screening of source of oxidants,
bases, and various temperatures has been pursued. As shown, the
11
5b
of anisaldehyde with traditional oxidants H
2
O
2
or oxone oc-
curs with formation of over-oxidized products and thus lower
yields: 31 or 46%, respectively. The direct oxidation of alkyl and
aryl-substituted aldehydes (entries 9e11) were smoothly oxi-
dized under these reaction conditions. Such as oxidation of
methyl, tert-butyl, phenyl-substituted aldehydes proceeded
conveniently to furnish the desired carboxylic acids 2iek in
excellent yields (entries 9e11). Then, substrates with electron-
withdrawing groups were tested to this oxidation protocol. To
our surprise oxidation of electron-withdrawing substrates 4-
nitro- and 3-nitro-benzadehydes were readily oxidized to the
ꢀ
oxidation of 3a at 25 C did not exhibit any observable reactivity in
this reaction condition (Table 1, entry 1). When the reaction was
ꢀ
heated at 60 C, it gave 43% yield of 2b (entry 2) and the remaining
reactant 3a had been recovered. Increasing the amount of aq 70%
TBHP to 3 equiv gave 60% yield of 2b (entry 3). A controlled ex-
periment had confirmed that in absence of base no product was
formed. The yield of 2b was improved noticeably when the reaction
ꢀ
was carried out at 60e70 C employing 3 equiv of both oxidant and
base (77% & 80%, entry 5). Subsequently, increasing the reaction
ꢀ
temperature to 80 C led to a much better yield of 2b in 84% (entry
4
9
-nitrobenzoic acid (2l) and 3-nitrobenzoic acid (2m) in 95% and
2% yields, respectively (entries 12 & 13). However, previously
6). Although the yield of 2b was much improved, still some of the
unreacted 3a was recovered from the reaction residue. For the
purpose of complete consumption of 3a, the amount of oxidant was
increased to 4 equiv. Indeed, it produced 2b in excellent 96% yield
described methods need prolong reaction time (>40 h) to the
2
1,22
oxidation of aldehydes having electron-withdrawing groups.
The presence of other functional groups, such as hydroxyl group
was found to be inert; in this case such aldehydes were selec-
tively converted to corresponding carboxylic acids without af-
fecting hydroxyl group (entry 14). As expected, oxidations of
non-benzylic or aliphatic aldehydes (entries 15e17) were selec-
tively oxidized to give the desired products 2o or 2peq in good
yields.
(
entry 7). Similar results were obtained employing alternate source
of base KOH, benzoic acid 2b was obtained in excellent yield (95%).
While the use of alternate sources of base, such as pyridine, Et N,
NH, rather poor performances were observed as compared
3
i
and Pr
2
to the conditions using the alkaline base (entries 7e8). To find out
alternate source of oxidants, reactions using various oxidants, such
as aq H O , TEMPO, oxygen, and NMO were carried out. Yet, no
2 2
significant improvement in the oxidation process was observed
(entries 12e15). Thus, the optimal condition for the direct oxidative
cleavage of vic-diols involved the combination of aq 70% TBHP
2
.2. Oxidation of diols
ꢀ
The present protocol, oxidation of aldehydes prompted us to
(4 equiv)/t-BuOK (3 equiv) and reacts at 80 C (entry 7).
investigate the oxidation of diols in aqueous medium. Therefore,
Encouraged by these results, the scope of this methodology to
to find out whether there is any selectivity in the oxidation of
the oxidation of various aromatic as well as aliphatic vic-diols was

8932
T.M. Shaikh, F.-E. Hong / Tetrahedron 69 (2013) 8929e8935
extended and investigated. The results are presented in Table 4. In
all the subsequent reactions, the optimized reaction condition as
described above (Table 3, entry 7) had been used. The diols derived
Table 4 (continued)
Product (2)b
Yield (%)c
Entry
Diol (3)
from a- and b-substituted methyl styrenes (3b and 3c) was sub-
jected to the oxidation, which gave the corresponding benzoic acids
in excellent yields (Table 4, entries 2 & 3).
7
8
2-Chlorobenzoic acid (2r)
90
Table 3
a
Optimization of oxidation of diols
2-Bromobenzoic acid (2e)
94
ꢀ
Yield (%)b,c
Entry
Oxidant (equiv)
Additive (equiv)
Temp ( C)
1
2
3
4
5
6
7
8
9
TBHP (2)
TBHP (2)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (4)
TBHP (3)
TBHP (4)
TBHP (4)
TBHP (4)
t-BuOK (1)
t-BuOK (1)
t-BuOK (2)
None
t-BuOK (3)
t-BuOK (3)
t-BuOK (3)
25
60
60
60
60
80
80
80
80
80
80
80
80
80
80
nr
43
60
d
9
4-Bromobenzoic acid (2a)
4-Methoxybenzoic acid (2f)
96
85
77(80)d
84
96 (95)e
63
K
3
PO
Pyridine (4)
Et N (4)
4
(3)
nr
nr
nr
nr
nr
nr
10
10
11
12
13
14
15
3
10
i
NH Pr
2
(4)
H
2
O
2
(6)
t-BuOK (4)
t-BuOK (4)
t-BuOK (4)
t-BuOK (4)
TEMPO
O
2
NMO
1
1
3-Nitrobenzoic acid (2m)
76
a
Reaction conditions: diol 3a (0.5 mmol), oxidant, additive, water (0.5 mL), 8 h;
acidic work-up.
b
Isolated yield.
c
Products were characterized by mp, 1H, 13C NMR, and GCeMS.
d
e
ꢀ
Reaction was carried out at 70 C.
Reaction was carried out in the presence of KOH.
1
1
2
3
4-Nitrobenzoic acid (2l)
80
86
Table 4
a
Oxidation of diols to carboxylic acids
2-Methylbenzoic acid (2h)
Entry
Diol (3)
Product (2)b
Yield (%)c
1
Benzoic acid (2b)
96
1
1
4
5
4-Methylbenzoic acid (2i)
87
2
3
Benzoic acid (2b)
Benzoic acid (2b)
88
92
4-tert-Butylbenzoic acid (2k) 92
16
17
18
2-Naphthoic acid (2k)
Benzoic acid (2b)
Benzoic acid (2b)
87
70
80
4
5
Benzoic acid (2b)
Benzoic acid (2b)
99
98
6
3-Fluorobenzoic acid (2d)
87
19
Benzoic acid (2b)
74

T.M. Shaikh, F.-E. Hong / Tetrahedron 69 (2013) 8929e8935
8933
Table 4 (continued )
Table 5
a
Oxidation of aliphatic diols to carboxylic acids
Entry
Diol (3)
Product (2)b
Yield (%)c
Entry
1
Diol (3)
Productb
Yield (%)c
Hexanoic acid (2p)
Pentanoic acid (2q)
59
54
20
Benzoic acid (2b)
68
a
Reaction conditions: diol (0.5 mmol), aq 70% TBHP (2 mmol), t-BuOK (1.5 mmol),
2
ꢀ
H
2
O (0.5 mL), 80 C, 8 h; acidic work-up.
b
Products was characterized by mp H, 13C NMR and GCeMS.
Isolated yield.
1
c
3
4
Butyric acid (2u)
Butyric acid (2u)
60
64
Moreover, the diols derived from stilbene, both trans (3d) and cis
3e) derivatives were smoothly converted to the corresponding
(
carboxylic acids in 99% and 98% yield, respectively (entries 4 & 5).
We were intrigued by the ways in which the oxidation was pro-
ceeded. Furthermore, a variety of substituted aromatic diols with
fluoro-, chloro-, and bromo-substituent under these reaction con-
ditions were screened. The diol derived from 3-fluorostyrene (3f)
resulted in the formation of 3-fluorobenzoic acid in 87% yield (entry
5
Acetic acid (2v)
68
6
2
). By contrast, other halo substituted diols derived from 2-chloro-,
-bromo-, and 4-bromo styrene (3gei), underwent oxidation to
a
Reaction conditions: diol (0.5 mmol), aq 70% TBHP (2 mmol), t-BuOK (1.5 mmol),
ꢀ
H
2
O (0.5 mL), 80 C, 8 h; acidic work-up.
b
Product was characterized by mp 1H, 13C NMR, and GCeMS.
Isolated yield.
produce the corresponding carboxylic acids in 90%, 94%, and 96%
yields, respectively (entries 7e9). In addition, the scope of this re-
action was evaluated by subjecting some electron-donating and
electron-withdrawing diols to the test. Thus, the diols prepared
from 4-methoxy-(3j) and 3-nitro-(3k) or 4-nitrostyrene (3l) were
easily undergone oxidation and led to the formation of the corre-
sponding benzoic acids in 89%, 76%, and 80% yield, respectively
c
GCeMS.34a Under the standard reaction conditions (footnote of
Table 4) the formation of benzaldehyde (1a) has been detected
within 3 h. Next, we performed reaction at 50 C employing TBHP/
t-BuOK (4 equiv each) in aqueous medium. In this case the for-
mation of 3a, 1a and traces of a-hydroxy carboxylic acid (4) has
been observed by GCeMS.
oxidized to the corresponding
by oxidative decarboxylation to the corresponding aldehyde (1a).
Aldehyde 1a oxidized to unstable species 1b,
verted to 1c under basic conditions and then to carboxylic acid (2a).
ꢀ
(
entries 10e12). In the case of styrene diols with methyl as the
substituent on the ortho- or para- position of aromatic ring, the
corresponding carboxylic acids were obtained without observation
of any over-oxidized product. For example, the oxidation of 1-o-
tolylethane-1,2-diol (entry 13, 3m) and 1-p-tolylethane-1,2-diol
3
4a
Thus, we believe that the diol 3a
-hydroxy carboxylic acid 4 followed
a
3
4d
which later con-
(
entry 14, 3n) resulted in the formation of 2-methylbenzoic acid
and 4-methylbenzoic acid in 86% and 87% yield, respectively.
Similarly, the diols derived from bulky substituent 4-tert-butyl
styrene (3o) [4-tert-butylphenyl ethane-1,2-diol] and 2-
vinylnaphthalene (3p) [1-(naphthalen-2-yl)ethane-1,2-diol] gave
the corresponding carboxylic acid in 92% and 87% yield (entries 15
&
16). Furthermore, the scope of this reaction was also extended to
the functionalized diols bearing CO
2
R, CH X, and CH OAc group a-
2
2
to the diols. The diol prepared from trans-methyl cinnamate was
successfully underwent oxidation to produce the corresponding
carboxylic acid in 70% yield (entry 17). Similarly, the other
a-
branched diols were also undergone oxidative cleavage to afford
the corresponding two-carbon less benzoic acid in 80% and 74%
yield, respectively (entries 18 &19). The scope of this reaction could
also be extended to terminal triol (3t). It gave the corresponding
carboxylic acid in 68% yield under this reaction condition (entry
2
0).
Further exploration on the use of this protocol in the oxidation
Scheme 3.
of aliphatic diols 3uey was pursued as well and the results are
presented in Table 5. Thus, the diol derivatives (entries 1e5) were
subjected under the desired reaction conditions to furnish the
corresponding carboxylic acids in moderate to good yields. As
shown, the oxidative cleavage of aliphatic diol was less effective as
compare to that of oxidation of aromatic diol.
Furthermore, to confirm this speculation, the separately pre-
pared 1a and 4 were subjected to this oxidation process. It was
found that these two compounds were converted to carboxylic acid
smoothly. The oxidation of 3b to benzoic acid (2b) did not proceed
through the mechanism described in Scheme 3.
2
.3. Mechanistic studies (oxidation of diol)
The proposed reaction pathway for the direct oxidative cleavage
3. Conclusion
of diol (3a) to carboxylic acid (2a) is shown in Scheme 3. To probe
the formation of probable intermediates, we have conducted a few
experiments and fraction of reaction mixtures were analyzed by
We have demonstrated transition metal-free a very effective,
practical, and inexpensive method for oxidation of aldehydes and

8934
T.M. Shaikh, F.-E. Hong / Tetrahedron 69 (2013) 8929e8935
diols with readily available aq 70% TBHP and commercial t-BuOK
in aqueous medium. The outcome of the present research is that,
aldehydes are conveniently oxidized to the corresponding car-
boxylic acids in excellent yields under mild reaction conditions.
Unlike known methods employing aq TBHP oxidant, the present
method does not need any transition metals. Notably, we did not
observe any over-oxidized side product, such as phenols. Fur-
thermore, diols are also oxidized to the corresponding carboxylic
acids. These reactions can often be performed without organic
solvents, thus improving the environmental impact of these oxi-
dative transformations, which traditionally generate much or-
ganic and toxic metal waste. Carboxylic acids are obtained by
simple filtration technique, thus, free from any chromatographic
purification.
4.1.2.2. Benzoic acid (2b). White solid; mp: 123e126 C (lit.35
ꢀ
ꢀ
ꢂ1
124e126 C); IR (KBr, cm ): 3438, 2914, 1715, 1699, 1455, 1282,
1
3
934, 708; H NMR (400 MHz, CDCl ): d 7.48 (2H, t, J 7.6 Hz), 7.62 (2H,
13
t, J 6.8 Hz), 8.12 (1H, d, J 7.2 Hz); C NMR (100 MHz, CDCl
3
):
d
128.4,
129.2, 130.2, 133.8, 172.4.
ꢀ
4.1.2.3. 4-Chlorobenzoic acid (2c). White solid; mp: 235e237 C
(lit.35 236e237 C); IR (KBr, cm ): 3010,1685, 640; H NMR (400 MHz,
ꢀ
ꢂ1
1
1
3
CDCl
3
þDMSO-d
6
):
d
7.34 (2H, d, J 2.3 Hz), 7.90 (2H, d, J 1.6 Hz); C NMR
): 128.7, 129.6, 137.5, 133.6, 164.3.
(100 MHz, CDCl
3
þDMSO-d
6
d
ꢀ
4.1.2.4. 3-Fluorobenzoic acid (2d). Solid; mp: 122e123 C; IR
ꢂ1
1
(KBr, cm ): 3441, 1711, 1684, 1541, 1507; H NMR (400 MHz,
CDCl ): 7.32 (1H, s), 7.45 (1H, d, J 5.6 Hz), 7.80 (1H, d, J 8.4 Hz),
.91 (1H, d, J 6.8 Hz); C NMR (100 MHz, CDCl
3
d
13
7
3
): d 116.9, 117.1,
4
4
. Experimental
120.8, 121.0, 125.9, 130.1, 130.2, 131.5, 131.4, 161.3, 163.7, 171.2.
ꢀ
.1. General information
4.1.2.5. 2-Bromobenzoic acid (2e). Solid; mp: 147e149 C; IR
ꢂ1
1
(
KBr, cm ): 2980, 2865, 1699, 1460, 1310, 920, 734; H NMR
(400 MHz, CDCl ): 7.14e7.44 (2H, m), 7.46e7.50 (2H, m);
C NMR (100 MHz, DMSO-d ):
All deuterated solvents were purchased from Aldrich. NMR
3
þDMSO-d
6
d
1
3
spectra were recorded on an Oxford Mercury 400 MHz spectrom-
eter. Tetramethylsilane (TMS) was used as a reference (0.00 ppm)
6
d
120.0, 127.7, 130.6, 132.5, 133.8, 167.4.
ꢀ
for all spectra. NMR spectra were recorded in CDCl
3
and DMSO-d
H NMR data are reported as follows: chemical shift (in parts per
million,
), integration, multiplicity (s¼singlet, d¼doublet,
t¼triplet, br s¼broad singlet) and coupling constants (in Hertz).
NMR chemical shifts are reported in ppm utilizing the central
resonance of the CDCl absorption as a reference (77.0 ppm). The
6
.
4.1.2.6. 4-Methoxybenzoic acid (2f). Solid; mp: 182e183
C
1
(lit.35 181e183 C); IR (KBr, cm ): 3447, 1717, 1653, 1383; H NMR
ꢀ
ꢂ1
1
d
6
(400 MHz, DMSO-d ): d 3.7 (3H, s), 6.98 (2H, d, J 8.6 Hz), 7.88 (2H, d,
1
3
13
C
J 8.4 Hz), 12.5 (1H br s); C NMR (100 MHz, DMSO-d
6
):
d
54.1, 112.3,
122.0, 130.4, 161.8, 166.6.
3
ꢀ
analysis on GCeMS was taken on Hewlett Packard 5890 series. IR
experiments were performed on a Bruker TENSOR-27. Thin layer
chromatography was performed on silica gel coated glass plates
4.1.2.7. 3-Methoxybenzoic acid (2g). Solid; mp: 182e184 C; IR
(KBr, cm ): 3440, 1712, 1653; H NMR (400 MHz, DMSO-d
ꢂ1
1
6
): d 3.8
(3H, s), 7.2 (1H, dd, J 4.0 Hz), 7.4 (1H, t, J 8.0 Hz), 7.5 (1H, s), 7.6 (1H,
13
(
250
mm, F-254), and spots were visualized with either 254 nm
6
d, J 8.0 Hz); C NMR (100 MHz, DMSO-d ): d 53.4,112.3,116.3,119.9,
ultraviolet light or a phosphomolybdic acid stain.
127.6, 130.6, 157.5, 165.6.
4
.1.1. Typical experimental procedure for oxidation of aldehydes to
4.1.2.8. 2-Methylbenzoic acid (2h). White color solid; mp:
ꢀ
ꢂ1
1
carboxylic acids (2aeq). In a 25 mL round-bottom flask, t-BuOK
104e105 C; IR (KBr, cm ): 3448, 1712, 1653, 1457, 1507, 1110; H
NMR (400 MHz, CDCl ): 2.40 (3H, s), 7.32 (1H, t, J
þDMSO-d
7.2 Hz), 7.43e7.86 (3H, m); C NMR (100 MHz, CDCl ):
þDMSO-d
21.2, 125.5, 128.2, 130.1, 131.4, 132.8, 139.0, 168.5.
(
(
0.5 mmol) was dissolved in water (1 mL), and an aldehyde
0.5 mmol) was added. Subsequently, aq 70% TBHP (1 mmol) was
3
6
d
13
3
6
ꢀ
slowly added to this flask. The resulting slurry was stirred at 60 C
or (optional) 25 C for 5 h or 40 h. After completion of reaction this
slurry was cooled to room temperature. The slurry was then acid-
ified with 2 M hydrochloric acid until the aqueous layer was
strongly acidic by pH paper. This on simple filtration resulted in
pure carboxylic acids.
d
ꢀ
ꢀ
4.1.2.9. 4-Methylbenzoic acid (2i). White solid; mp: 174e176 C
3
5
ꢀ
ꢂ1
(lit. 174e176 C); IR (KBr, cm ): 3441, 1705, 1651, 1507, 1084, 980;
1
H NMR (400 MHz, DMSO-d
6
):
7.81 (2H, d, J 6.4 Hz); C NMR (100 MHz, DMSO-d
29.1, 129.4, 143.0, 167.4.
d 2.32 (3H, s), 7.26 (2H, d, J 8.0 Hz),
13
6
):
d
21.1, 128.1,
1
4
.1.2. Typical experimental procedure for oxidation of diols to car-
boxylic acids (3aet). In a 25 mL round-bottom flask, t-BuOK
1.5 mmol) was dissolved in water (0.5 mL), and diol (0.5 mmol)
ꢀ
4.1.2.10. 4-tert-Butylbenzoic acid (2j). Solid; mp: 162e164 C; IR
ꢂ1
1
(
(KBr, cm ): 3446, 1717, 1699, 1684, 1457, 1384, 1285, 890; H NMR
(400 MHz, CDCl ): 1.04 (9H, s), 7.19 (2H, d, J 8.4 Hz),
was added. Subsequently, aq 70% TBHP (2 mmol) was slowly added
to this flask. The resulting suspension was then heated at 80
3
þDMSO-d
6
d
ꢀ
13
C
7.72 (2H, d, J 8.0 Hz); C NMR (100 MHz, CDCl
3
þDMSO-d
6
): d 30.4,
(
using oil bath) for 8 h. After completion of reaction this slurry was
38.8, 124.5, 127.4, 128.8, 155.5, 167.7.
cooled to room temperature. The slurry was then acidified with 2 M
hydrochloric acid until the aqueous layer was strongly acidic by pH
paper. This on simple filtration resulted in pure carboxylic acids.
Note: alternate work-up procedure: The reaction mixture was
then cooled to room temperature and then extracted with ethyl
acetate (2ꢁ10 mL) and combined organic phase was washed with
0
4.1.2.11. (1,1 -Biphenyl)-4-carboxylic acid (2k). Solid; mp:
ꢀ
ꢂ1
223e225 (lit. 222e225 C); IR (KBr, cm ): 1674, 1607, 1357, 1286,
1190, 1045, 862, 790, 695; H NMR (400 MHz, CDCl
7.27e7.38 (3H, m), 7.52e7.58 (4H, q, J 8.0, 12.0 Hz), 8.02 (2H, d, J
12.0 Hz); C NMR (100 MHz, CDCl
1
3
þDMSO-d
6
):
d
13
3
þDMSO-d
6
):
d
126.4, 126.7,
2 4
saturated brine solution and dried over anhydrous Na SO . After
127.5, 128.4, 128.7, 129.8, 139.5, 145.4, 168.5.
removal of the solvent under reduced pressure to afford carboxylic
acids.
ꢀ
4.1.2.12. 4-Nitrobenzoic acid (2l). Solid; mp: 238e240 C; IR
ꢂ1
1
(
KBr, cm ): 3443, 1715, 1699, 1457, 1211; H NMR (400 MHz,
13
4
.1.2.1. 4-Bromobenzoic
acid
52e253 C; IR (KBr, cm ): 3411, 1710, 1684, 1385, 640; H NMR
400 MHz, CDCl ): 7.49 (2H, d, J 2.4 Hz), 7.79 (2H, d, J
þDMSO-d
.6 Hz); 13C NMR (100 MHz, CDCl
þDMSO-d ): 126.3, 128.8, 130.1,
30.4, 166.2.
(2a). White
solid;
mp:
DMSO-d
6
):
d
8.12 (2H, d, J 8.4 Hz), 8.27 (2H, d, J 8.0 Hz); C NMR
): 123.7, 130.7, 136.4, 150.0, 165.8.
ꢀ
ꢂ1
1
2
(100 MHz, DMSO-d
6
d
(
3
6
d
ꢀ
4.1.2.13. 3-Nitrobenzoic acid (2m). Solid; mp: 139e140 C; IR
(KBr, cm ): 3442, 1711, 1699, 1211; H NMR (400 MHz, DMSO-d ):
1
1
3
6
d
ꢂ1
1
6

T.M. Shaikh, F.-E. Hong / Tetrahedron 69 (2013) 8929e8935
8935
d
7.75 (1H, t, J 8.0 Hz), 8.27e8.54 (2H, m), 8.55 (1H, s); 13C NMR
100 MHz, DMSO-d ): 122.1, 125.2, 128.2, 131.0, 133.5, 146.1, 163.8.
M. B.; March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and
Structure, 5th ed.; Wiley-Interscience: New York, NY, 2001; pp 917e919.
. (a) Bowden, K.; Heilbron, I. M.; Jones, E. R. H.; Weedon, B. C. L. J. Chem. Soc. 1946,
(
6
d
3
39e45; (b) Heilbron, I.; Jones, E. R. H.; Sondheimer, F. J. Chem. Soc. 1949,
4
.1.2.14. 2-Hydroxy-5-nitrobenzoic
acid
(2n). Solid; mp:
604e607; (c) Bladon, P.; Fabian, J. M.; Henbest, H. B.; Koch, H. P.; Wood, G. W. J.
Chem. Soc. 1951, 2402e2411; (d) Curtis, R. G.; Heilbron, I.; Jones, E. R. H.; Woods,
G. F. J. Chem. Soc. 1953, 457e464; (e) Bowers, A.; Halsall, T. G.; Jones, E. R. H.;
Lemin, A. J. J. Chem. Soc. 1953, 2548e2560; (f) Djerassi, C.; Engle, R. R.; Bowers,
A. J. Org. Chem. 1956, 21, 1547e1549; (g) Hainess, A. H. Methods for the Oxidation
of Organic Compounds; Academic: New York, NY, 1988221; 423; (h) Ogliaruso,
M. A.; Volfe, F. A. In Updates From the Chemistry of Functional Groups In
Synthesis of Carboxylic Acids Esters and Their Derivatives; Patai, S., Rappoport, Z.,
Eds.; Wiley: Chichester, UK, 1991; p 357.
4. Cainelli, G.; Cardillo, G. Chromium Oxidations in Organic Chemistry; Springer:
Berlin, 1984.
. (a) Webb, K. S.; Ruszkay, S. J. Tetrahedron 1998, 54, 401e410; (b) Travis, B. R.;
Sivakumar, M.; Hollist, G. O.; Borhan, B. Org. Lett. 2003, 5, 1031e1034.
. Hajimohammadi, M.; Safari, N.; Mofakham, H.; Shaabani, A. Tetrahedron Lett.
ꢀ
ꢂ1
2
1
(
8
29e230 C; IR (KBr, cm ): 3197, 3102, 3071, 2630, 2576, 2522,
1
626, 1580, 1616, 1475, 1376, 1151, 1075, 868, 960, 652, 600; H NMR
400 MHz, DMSO-d ): 5.7 (1H, s), 6.9 (1H, d, J 12.0 Hz), 7.1 (1H, s),
.8 (1H, s), 10.8 (1H, br s); C NMR (100 MHz, DMSO-d
18.6, 126.3, 131.0, 139.3, 165.3, 171.5.
6
d
13
6
): d 113.7,
1
.1.2.15. 3-Phenylpropanoic acid (2o). 1
CDCl ): 2.71 (2H, t, J 7.5 Hz), 2.9 (2H, t, J 7.5 Hz),
ꢂDMSO-d
.26e7.33 (5H, m); C NMR (100 MHz, DMSO-d
26.3, 128.2, 128.5, 140.2, 179.2.
4
H NMR (400 MHz,
3
6
d
5
13
7
1
6
): d 30.6, 35.5,
6
2010, 51, 4061e4065.
7
. Nair, V.; Varghese, V.; Paul, R. R.; Jose, A.; Sinu, C. R.; Menon, R. S. Org. Lett. 2010,
12, 2653e2655.
ꢂ1
4
.1.2.16. Hexanoic acid (2p). Liquid; IR (KBr, cm ): 2972, 2960,
1
1
8
1
3
721, 1421, 1294, 948; H NMR (400 MHz, CDCl
3
):
d
0.82 (3H, t, J
8. Murray, A. T.; Matton, P.; Fairhurst, N. W. G.; John, M. P.; Carbery, D. R. Org. Lett.
2
012, 14, 3656e3659.
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0. (a) Yamada, T.; Rhode, O.; Takai, T.; Mukaiyama, T. Chem. Lett. 1991, 5e10; (b)
Grill, J. M.; Ogle, J. W.; Miller, S. A. J. Org. Chem. 2006, 71, 9291e9296.
1. (a) W oꢀ jtowicz, H.; Brzaszcz, M.; Kloc, K.; M1ochowski, J. Tetrahedron 2001, 57,
743e9748; (b) M1ochowski, J.; Brzaszcz, M.; Giurg, M.; Palus, J.; W oꢀ jtowicz, E.
.0 Hz), 1.22e1.26 (4H, m), 1.54e1.55 (2H, m), 2.25e2.29 (2H, m),
9
1
0.2 (1H, br s); 13C NMR (100 MHz, CDCl
1.1, 33.7, 33.9, 180.3.
):
d
13.7, 22.1, 24.2, 26.6,
3
1
9
ꢂ1
4
.1.2.17. Pentanoic acid (2q). Liquid; IR (KBr, cm ): 3481, 2950,
Eur. J. Org. Chem. 2003, 22, 4329e4339.
1
2
1
d
910, 1702, 1320; H NMR (400 MHz, CDCl
3
): 0.91e0.99 (3H, m),
.20e1.68 (5H, m), 2.32e2.38 (1H, m); 1 C NMR (100 MHz, CDCl
3
)
d
12. Heaney, H.; Newbold, A. J. Tetrahedron Lett. 2001, 42, 6607e6609.
13. Sato, K.; Takagi, J.; Aoki, M.; Noyori, R. Tetrahedron Lett. 1998, 39, 7549e7952.
3
14. (a) Bhatia, B.; Punniyamurthy, T.; Iqbal, J. J. Org. Chem. 1993, 58, 5518e5523; (b)
13.5, 22.1, 26.6, 33.7, 180.3.
Kharata, A. N.; Pendleton, P.; Badalyan, A.; Abedini, M.; Amini, M. M. J. Mol.
Catal. A: Chem. 2001, 175, 277e283.
.1.2.18. 2-Chlorobenzoic acid (2r). Solid; mp: 139e140 ꢀC; 1
NMR (400 MHz, DMSO-d ): 7.13e7.67 (m, 3H), 7.8 (1H, d), 13.01
1H, br s); 13C NMR (100 MHz, DMSO-d
31.4, 132.3, 166.1.
15. Lim, M.; Yoon, C.-M.; An, G.; Rhee, H. Tetrahedron Lett. 2007, 48, 3835e3839.
4
H
16. (a) Jiang, N.; Ragauskas, A. J. J. Org. Chem. 2007, 72, 7030e7033; (b) Gopinath,
6
d
R.; Patel, B. K. Org. Lett. 2000, 2, 577e579.
17. Rozner, D. S.; Neimann, K.; Neumann, R. J. Mol. Catal. A: Chem. 2007, 262,
(
1
6
):
d
127.1, 130.3, 130.5, 131.2,
1
09e113.
8. Biella, S.; Prati, L.; Rossi, M. J. Mol. Catal. A: Chem. 2003, 197, 207e212.
9. Sedelmeier, J.; Ley, S. V.; Baxendale, I. R.; Baumann, M. Org. Lett. 2010, 12,
1
1
ꢀ
4
.1.2.19. 2-Naphthoic acid (2s). Solid; mp: 185e186 C; IR (KBr,
3618e3621.
ꢂ1
1
cm ): 3447, 1712, 1647, 1383, 780; H NMR (400 MHz, DMSO-d
6
):
20. Mannam, S.; Sekar, G. Tetrahedron Lett. 2008, 49, 1083e1086.
21. Chakraborty, D.; Gowda, R. R.; Malik, P. Tetrahedron Lett. 2009, 50, 6553e6556.
d
7.53e7.64 (2H, m), 7.97 (3H, d, J 12.4 Hz), 8.08 (1H, d, J 8.4 Hz), 8.61
2
2
2. Malik, P.; Chakraborty, D. Tetrahedron Lett. 2010, 51, 3521e3523.
3. Zhang, J.; Wang, Z.; Wang, Y.; Wan, C.; Zheng, X.; Wang, Z. Green Chem. 2009, 11,
1973e1978.
13
(
6
1H, s), 13.01 (1H, br s); C NMR (100 MHz, DMSO-d ): d 125.2,
126.8, 127.6, 128.1, 128.3, 129.2, 130.5, 132.1, 134.9, 167.5.
24. (a) Bernini, R.; Coratti, A.; Provenzano, G.; Fabrizi, Z.; Tofani, D. Tetrahedron
2
005, 61, 1821e1825; (b) Please see Ref. 11.
4
.1.2.20. Butyric acid (2s). Liquid; 1H NMR (400 MHz, CDCl
0.87e0.97 (3H, m), 1.58e1.70 (2H, m), 2.29e2.35 (2H, q, J 7.2,
3
):
2
5. (a) Ishii, Y.; Yamawaki, K.; Yoshida, T.; Ura, T.; Ogawa, M. J. Org. Chem. 1987, 52,
1868e1870; (b) Kaneda, K.; Morimoto, K.; Imanaka, T. Chem. Lett. 1988,
1295e1296; (c) Ishii, Y.; Yamawaki, K.; Ura, T.; Yamada, H.; Yoshida, T.; Ogawa,
M. J. Org. Chem. 1988, 53, 3587e3593.
6. Criegee, R. Chem. Ber. 1931, 64, 260e266.
7. (a) Iwahama, T.; Yoshino, Y.; Keitoku, T.; Sakaguchi, S.; Ishii, Y. J. Org. Chem.
d
.2 Hz), 11.0 (1H, br s); 1 C NMR (100 MHz, CDCl
80.3.
3
4
1
3
): d 13.4, 18.0, 35.9,
2
2
2
000, 65, 6502e6507; (b) Mastrorilli, P.; Surama, G. P.; Nobile, C. F.; Farinola, G.;
Acknowledgements
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Financial support for this work was provided by the National
Science Council, Taiwan (Res. Grant: NSC 101-2113-M-005-011-
MY3).
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3
1. Pl. see Ref. 10(b).
Supplementary data
32. (a) Hong, Z.; Liu, L.; Sugiyama, M.; Fu, Y.; Wong, C.-H. J. Am. Chem. Soc. 2009, 131,
8
352e8353; (b) Nicolaou, K. C.; Adsool, V. A.; Hale, C. R. H. Org. Lett. 2010, 12,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.07.101.
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2
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