Iodosobenzoic Acid (IBA) Catalysed Benzylic and Aromatic C–H Oxidations

Article abstract of DOI:10.1007/s10562-017-2050-4

Abstract: A metal-free reusable hypervalent iodine(III) reagent is employed as a stable catalyst for the selective oxidation of active methylenes, indoles and styrene C–H bond to corresponding carbonyl compounds. From both economic and environmental point of view use of 2-Iodosobenzoic acid for oxidations replacing metals, makes the reaction interesting. Graphical Abstract: A metal-free reusable hypervalent iodine(III) reagent is employed as a stable catalyst for the selective oxidation of active methylenes, Indoles and styrene C–H bond to corresponding carbonyl compounds. From both an economic and environmental point of view use of oxygen as the oxidant, makes the reaction interesting. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s10562-017-2050-4

Catal Lett
DOI 10.1007/s10562-017-2050-4
Iodosobenzoic Acid (IBA) Catalysed Benzylic and Aromatic C–H
Oxidations
1
1
1,2
Vittam Hima Bindu · Sai Prathima Parvathaneni · Vaidya Jayathirtha Rao
Received: 16 January 2017 / Accepted: 29 March 2017
©
Springer Science+Business Media New York 2017
Abstract A metal-free reusable hypervalent iodine(III)
reagent is employed as a stable catalyst for the selective
oxidation of active methylenes, indoles and styrene C–H
bond to corresponding carbonyl compounds. From both
economic and environmental point of view use of 2-Iodoso-
benzoic acid for oxidations replacing metals, makes the
reaction interesting.
Keywords Hypervalent iodine · Iodosobenzoic acid
(IBA) · Oxidation · DMSO · Carbonyl compounds
1 Introduction
The oxidation of the olefinic and benzylic methylene
groups to the corresponding carbonyl derivatives is con-
sidered to be one of the fundamental methods for C–H
functionalization [1]. This is a highly important synthetic
transformation of great interest particularly attractive for
industrial processes. The carbonyl compounds have been
recognized as building blocks in natural products and phar-
maceutical compounds with unique properties [2–5].
Graphical Abstract A metal-free reusable hypervalent
iodine(III) reagent is employed as a stable catalyst for the
selective oxidation of active methylenes, Indoles and sty-
rene C–H bond to corresponding carbonyl compounds.
From both an economic and environmental point of view
use of oxygen as the oxidant, makes the reaction interesting.
Oxidations are typically performed with organic perox-
ides in combination with transition metal derivatives [6–10].
Due to the high toxicity associated with these processes,
there is a definite need to develop catalytic oxidations under
mild conditions [11]. In the last few years the demand for
efficient and environmentally benign oxidative transforma-
tions has increased and particularly metal-free oxidations
have been developed [12]. Molecular oxygen is ubiquitous,
inexpensive and greener oxidant commonly employed on
the industrial scale, as it is atom efficient and produce water
as the only by-product [13, 14] Therefore, a lot of attention
has been devoted to the development of efficient oxidation
processes based on the combination of molecular oxygen
and atom economy [15, 16]. More specifically, the develop-
ment of a catalyst system combined with environmentally
benign oxidants decreasing the heavy metals for the direct
oxidations of the methylene group are highly desirable.
Hypervalent iodine(III) compounds are attractive rea-
gents extensively employed in organic synthesis as highly
selective and environmentally friendly oxidizing reagents
[17–26]. In particular benziodoxole-based reagents are
OH
I
O
O
IBA C
O
o
CH CN, O , 80 C
3
2
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-017-2050-4) contains supplementary
material, which is available to authorized users.
*
Sai Prathima Parvathaneni
saiprathimaiict@gmail.com
*
Vaidya Jayathirtha Rao
jrao@iict.res.in
1
2
Crop Protection Chemicals Division, Indian Institute
of Chemical Technology, Hyderabad 500607, India
AcSIR, Organic-II, Indian Institute of Chemical Technology,
Hyderabad 500607, India
Vol.:(0
1
123456789)
3

V. H. Bindu et al.
especially important in which iodine and oxygen are incor-
porated in a heterocyclic five- membered ring with high
thermal stability and a useful reactivity pattern compared
to that of the analogous non cyclic derivatives [27–30].
Hypervalent iodine heterocycles derived from benziodox-
oles with pentavalent iodine are Dess–Martin periodi-
nane (DMP, A) [31–36] and 1-hydroxy-1, 2-benziodoxol-
2 Results and Discussion
Our initial investigation focused on identifying suitable
hypervalent iodine based catalytic system for selective
aerobic oxidation of active methylene groups to carbonyl
groups producing water as only by-product. Fluorene (1a)
was selected as a model substrate to identify the suitable
catalytic system (Table 1). Reactions were carried with
3
-(1H)-one-1-oxide (IBX, B) [37–43] have emerged as the
versatile reagents for selective oxidative transformations.
OAc
AcO
O
OH
O
OH
OAc
I
I
I
O
O
O
O
O
DMP (12-I-5) A
IBX B
IBA (10-I-3) C
Recently benzylic oxidation has been reported by
cyclic iodine(III) compounds and by pentavalent iodine,
o-iodoxybenzoic acid (IBX) to arylketones [44–46]. Ozone
also have been explore to benzylic oxidations to carbonyl
compounds [47–49]. However the reported methods
endure from low solubility and high explosive nature of
IBX restricts its practical application [50]. We have been
engaged in the synthetic utilization of trivalent organoio-
dine compounds for oxidation reactions, especially with
iodosobenzoic acid (IBA, C) as it is easy to handle and can
be recyclable compared to IBX [51].
readily available iodine based reagents iodobenzene, phe-
nyl iodine(III) diacetate (PIDA), 1-(tert-butylperoxy)-
1,2-benziodoxol-3(1H)-one (PIFA), iodoso benzoic acid
(IBA) by using TBHP as an external oxidant (entries 1–4).
Although PIDA gave 50% yield (entry 2), iodobenzene,
PIFA and IBA gave the desired product in 30, 20 and 40%
yield respectively (entries 1, 3 and 4). In terms of green
Table 1 Screening of hypervalent iodine induced oxidation reactions
In particular, we have previously found that the activation
of the IBA by inorganic salts (oxone) serves as a powerful
method for the in situ generation of IBX, the active iodine(V)
state using oxone from iodosobenzoic acid (IBA) as effec-
tive and unprecedented iodine(III)-induced oxidations [52,
Entry reagent
Oxidant
Solvent
Time (h)
Yielda
53]. However, there have been no reports on the catalytic
use of IBA for oxidation of active methylene groups to car-
bonyl compounds without employing external oxidant. Thus,
we sought to develop highly efficient benziodoxole derived
iodine(III)-analogous as catalysts for the oxidations with
1
2
3
4
5
6
7
8
9
1
1
1
PhI
TBHP
TBHP
TBHP
TBHP
O2
O2
O2
O2
O2
O2
–
CH CN
36
36
36
36
24
12
12
12
24
12
24
24
30
50
20
40
NR
20
NR
NR
84
60
3
PIDA
PIFA
IBA
IBA
IBA
IBA
IBA
IBA
CH CN
3
CH CN
3
CH CN
3
dioxygen (O )/DMSO under mild and metal-free conditions.
2
H O
2
In continuation to our interest to develop metal free
environmentally benign oxidative protocols with hyperva-
lent iodine reagents [54, 55], herein we report iodosoben-
zoic acid (IBA) catalysed oxidations by employing oxygen
as a co-oxidant (Scheme 1).
MeOH
Toluene
CH CN
3
b
CH CN
3
0 IBA
1 IBA
2 –
DMSO
CH CN
NR
NR
3
O
O2
CH CN
3
IBA C
All reactions were carried out at 1 mmol scale at room temperature in
2 mL of solvent, reagent (0.4 equiv) at room temperature
CH CN, O2
3
a
GC yield
b
Scheme 1 Hypervalent iodine(III) catalysed aerobic oxidation
Temperature at 80°C
1
3

Iodosobenzoic Acid (IBA) Catalysed Benzylic and Aromatic C–H Oxidations
chemical perspective we have chosen oxygen as an envi-
ronmentally safe co-oxidant and water as solvent for cata-
lytic hypervalent iodine oxidation at room temperature
with recyclable iodosobenzoic acid (IBA) (entry 5). This
was found to be ineffective even in presence of tempera-
ture. However the reaction was sluggish with MeOH as
solvent and the yield of 2a was only 20% (entry 6). But
with Toluene and CH CN the reaction did not proceed
3
with oxygen under low temperature conditions (entries 7
and 8). Then we have carried the reaction with only 0.4
equiv of IBA and oxygen balloon at 80°C, to give the
desired product 2a in 84% yield in CH CN within 24 h
3
(entry 9). Among the solvents screened CH CN found to
3
be suitable solvent system compared to other solvents.
Table 2 Oxidation of benzylic
methylene C–H with IBA/
Oxygen
a,b
a
b
c
c
c
a
b
b
a
b
b
d
All reactions were carried out at 1 mmol scale, IBA (0.4 equiv) in 2 mL of CH CN, 80°C
3
a
Isolated yield
IBA (0.2 equiv) with DMSO as solvent at 80°C
IBA (0.4 equiv) at room temperature with DMSO
No solvent
b
c
d
1
3

V. H. Bindu et al.
However the reaction proceeded to give the desired prod-
uct in 60% yield with DMSO as solvent (entry 10). As
expected the reaction did not proceed in the absence of
oxygen or IBA (entries 11 and 12).
in good yield with only DMSO solvent system (entry
6). But benzyl alcohol gave selectively aldehyde as sole
product both CH CN and DMSO solvent system (entry
3
7). Nonetheless, with the methylene group flanked by the
heteroatom nitrile and amine functionality showed resist-
ance to oxidation even under prolonged reaction condi-
tions (entries 8 and 9). Delightfully, the toluene methyl-
ene C–H bonds (Table 2, entry 10) were also successfully
oxidized under the developed conditions. But recovery
of starting material was observed in case of α-tetralone
(entry 11).
The generality of the IBA with oxygen/DMSO sys-
tem for oxidation of active methylene containing ben-
2
zylic C(sp ) C–H bond of various structurally diverse
substrates were examined under optimized reaction con-
ditions (Table 2). Fluorene (1a) afforded the oxidised
product fluorenone (2a) in 84% yield (entry 1). Interest-
ingly with increase in halogen substitution (bromo) with-
drawing group underwent smooth oxidation to afford
corresponding ketones (2b–d) in high yields (85–94%)
in shorter time periods (1–4 h) with DMSO as solvent
at room temperature (entries 2–4). Then, the reaction
was examined with oxindole oxidation to isatin, (entry
Furthermore, the reaction scope was examined with
oxidation of styrenes to corresponding aldehydes as repre-
sented in Table 3. Different substituents at the para posi-
tion of styrene such as methyl, methoxy, chloro, fluoro and
bromo were well tolerated and afforded the corresponding
aldehydes (4a–f) with 90–71% yields with DMSO solvent
system.
5
). It is interesting that the yield was increased from 40
to 78% with change in solvent from CH CN to DMSO,
3
but the starting material remained intact even with more
screening under various conditions (see supporting infor-
mation). However ethyl benzene gave the acetophenone
In addition, we also tested the reaction with indoles with
a series of functional groups, including methyl, fluoro,
chloro, and bromo were well tolerated under the optimal
Table 3 Oxidation of styrenes
a
with IBA
All reactions were carried out at 1 mmol scale, IBA (0.2 equiv) in 2 mL of DMSO, 80°C,
1
2 h
a
GC yield
1
3

Iodosobenzoic Acid (IBA) Catalysed Benzylic and Aromatic C–H Oxidations
Table 4 Oxidation of Indoles
E
a
with IBA
All reactions were carried out at 1 mmol scale, IBA (0.2 equiv) in 2 mL of DMSO, 80°C,
1
2 h
a
Isolated yield
o
100
IBA, CH3CN, 80 C
2
a, 84%
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
under O atmosphere
2
(a)
o
IBA, CH3CN, 80 C
NR
under N2 atmosphere
(b)
1a
o
1
2
3
4
IBA, CH CN, 80 C
3
NR
No of cycles
under vaccum
(c)
Fig. 1 Reusability of IBA C
o
IBA, DMSO, 80 C
d)
reaction conditions (Table 4). Isatin 6a could be obtained in
4% yield by direct oxidation of indole 5a under optimized
conditions by employing DMSO solvent system.
2a, 80%
(
8
Scheme 2 Experiments for mechanistic investigation
1
3

V. H. Bindu et al.
It should be noted that the reaction of 5c, 5d, 5e and
f could lead to desired products in 72, 81, 78 and 83%
3 Conclusions
5
respectively (entries 3–6). The 5-nitroindole 5b didn’t gave
the desired product as the nitro substituent showed signifi-
cant influence on the reaction yield (Table 4, entry 2). Thus
we were pleased with the results, as it provided oxidised
In conclusion, we have successfully developed a con-
venient, simple, metal-free procedure for the oxidation of
benzylic methylene groups to the corresponding carbonyl
derivatives. This represents a significant advancement in
the area of organocatalytic C–H bond activation with oxy-
gen/DMSO as oxidants under mild, metal free conditions.
This method has been proved to be more efficient as it nei-
ther utilizes the external oxidants nor metal oxidants, which
is highly desirable for environmentally benign C–H oxida-
tions. Further studies on this topic are underway for broad
scope, and the results will be reported in due course.
3
2
products for C(sp ), C(sp ) C–H bond oxidation of different
fluorene, styrene and indole derivatives.
In order to show the scale-up potential of this selective
transformation, we have conducted a gram-scale synthe-
sis of 2a from 1a (20 mmol), IBA (10 equiv) in 80 mL
of CH CN. The reaction mixture was subjected to four
3
bar pressure, with continuous flow of oxygen for about
4
h under 80 °C temperature in a autoclave reactor. This
Acknowledgements PSP gratefully acknowledge to the financial
assistance provided by CSIR-Senior Research Associateship (Scien-
tist’s Pool Scheme), New Delhi and VHB (JRF), thanks for the fellow-
ship provided by DST, Govt of India. We also acknowledge director
IICT for providing infrastructural facilities.
gave good yield of the desired product, demonstrating
the industrial viability for selective synthesis of oxidized
products. However in absence of oxygen supply in the
same reactor the reaction was abortive to produce the
desired product even after 12 h. At the end of reaction
the iodine reagent IBA C is easily separated by simple
filtration. Then we have tested the same reaction i.e., con-
version of 1a–2a to prove the recyclability of the catalyst.
We have tested the IBA C for four consecutive reactions
and observed it can be reused for four cycles without any
appreciable loss in its activity as shown in Fig. 1.
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