Co(ii), a catalyst for selective conversion of phenyl rings to carboxylic acid groups

Article abstract of DOI:10.1039/c4ra10510a

An inexpensive protocol for the conversion of -C₆H₄R into -COOH groups using Co(ii)-Oxone mixture as the catalytic system is described. A series of substrates containing substituted and non-substituted phenyl groups could be selectively converted into carboxylic acids. Initial mechanistic data have been provided.

Full text of DOI:10.1039/c4ra10510a

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Co(II), a catalyst for selective conversion of phenyl
rings to carboxylic acid groups†
Cite this: RSC Adv., 2014, 4, 49395
*
*
Shashi Bhushan Sinha, Jesus Campos, Gary W. Brudvig and Robert H. Crabtree
´
Received 25th August 2014
Accepted 25th September 2014
DOI: 10.1039/c4ra10510a
www.rsc.org/advances
An inexpensive protocol for the conversion of –C6H4R into –COOH identifying catalysts for such C–H bond oxidation reactions, but
groups using Co(II)–Oxone mixture as the catalytic system is since our initial catalyst was the water-soluble Co(II) ion, we
described. A series of substrates containing substituted and non- chose a water-soluble version of ethylbenzene, EBS (EBS ¼
substituted phenyl groups could be selectively converted into sodium 4-ethylbenzene sulphonate, 1), as our initial substrate.
carboxylic acids. Initial mechanistic data have been provided.
If water proved a viable solvent for a wider range of substrates, it
would be environmentally advantageous. Prior work on Co
catalysts for the selective oxidation of organic compounds
includes a number of homogeneous and heterogeneous cata-
lysts,7 usually involving various Co–ligand combinations, not
simple Co(II) ions as here.
EBS was selectively and efficiently oxidized using a simple
cobalt salt with Oxone as the primary oxidant. Cobalt(II) tetra-
uoroborate hexahydrate was chosen on account of its oxida-
tively stable counteranion. With 5 mol% catalyst loading and 4
equiv. of Oxone, sodium 4-acetylbenzene sulphonate (2) was
formed in 76% yield aer 11 h at 25 ꢀC. In control reactions
under the same conditions, 2 was barely detectable with Oxone
alone and entirely absent with Co(II) alone, so the combination
of the two is needed. The course of the catalytic reaction was
monitored by 1H NMR spectroscopy (Fig. 1). Phenylethyl alcohol
sulphonate (3), derived from initial hydroxylation, was observed
in small amounts (up to 10%) at intermediate reaction times,
but it was further oxidized to the ketone during the later course
of the reaction.
In a key observation, signicant amounts (15–20%) of propionic
acid (4), were also detected by 1H NMR in the products,
together with acetate and formate (Fig. S1, see ESI†). The peak
assignments were conrmed by the addition of authentic
samples of these products to the NMR solutions. Propionic acid
could only have plausibly been formed by oxidative degradation
of the benzene sulphonate group to –COOH, but this would
mean that the benzylic CH2 group had resisted attack, an
unexpected outcome. The other expected oxidation product
from the degradation of the benzene ring upon the initial
oxidation to 2, would be pyruvic acid, but it was not observed by
1H NMR spectroscopy. In a separate experiment, it was seen that
pyruvate is very readily converted to acetate under similar
reaction conditions so we would not have seen it even if it had
Aqueous Co(II) salts catalyze the decomposition of potassium
peroxymonosulfate (Oxone),1 and the Co(II)–Oxone combination
has been used extensively for water treatment and the complete
oxidative degradation of phenols, surfactants and dyes.2 Its
potential in synthetic oxidation does not yet seem to have been
explored, however. Development of mild and selective catalysts
for the functionalization of C–H bonds remains a major chal-
lenge in modern chemistry and nds important implications in
organic synthesis.3 During studies of the Co(II)–Oxone system
for the selective oxidation of C–H bonds, we found an unex-
pected conversion of phenyl rings into carboxylic acid groups.
This type of transformation makes the phenyl group a masked
carboxylic acid equivalent and, therefore, has signicance in
synthetic organic chemistry. Indeed, oxidative degradation of
arene rings to –COOH groups has seen extensive use, but the
classic cases involve the much more reactive 2-furyl groups as
the arene to be degraded.4 Even so, previous work has usually
involved harsh reagents and conditions as well as expensive
materials such as ruthenium salts.5,6 We have now achieved this
transformation with high selectivity under mild conditions in
water with inexpensive Co(II) as the catalyst. Moreover, instead
of the 2-furyl groups usually employed, the present system is
effective with the much more widely available phenyl
derivatives.
Our work started with the aim of seeing C–H oxidation
reactions from the Co(II)–Oxone system. The oxidation of
ethylbenzene to acetophenone is a useful initial screen for
Department of Chemistry, Yale University, 225 Prospect Street, New Haven,
Connecticut 06520, USA. E-mail: gary.brudvig@yale.edu; robert.crabtree@yale.edu
† Electronic supplementary information (ESI) available: Additional 1H NMR
spectra. See DOI: 10.1039/c4ra10510a
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Table 1 Optimization of the reaction conditionsa
Entry Cat. (%) Oxidanta
T (ꢀC) t (h) Yieldb M. B.c TONb
1
2
3
4
5
6
7
8
1
2.5
5
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
NaIO4
50
50
50
50
25
40
50
50
50
50
50
50
50
18
18
18
18
24
24
24
6
18
18
24
18
18
18
20
4
22
30
38
50
25
38
41
38
0
0
3
0
0
44
37
40
50
51
38
41
45
>95
>95
82
>95
>95
>95
75
21
12
8
10
5
5
5
5
5
5
5
5
5
5
5
5
5
—
—
—
—
—
—
—
—
—
—
—
—
9
10
11
12
13
14
Na2S2O8
Na2S2O8
H2O2 (aq.)
NaOCl
tBuOOH (aq.) 50
0
27
60
Fig. 1 Oxidation of ethyl benzene sulphonate at room temperature in 15d
Oxone
Oxone
50
40
the presence of Co(II)–Oxone. Reactions carried out in air; similar 16e
>95
results are obtained under nitrogen.
a
Reaction conditions: 2-phenylpyridine (10 mL, 0.07 mmol), Oxone (516
mg, 0.84 mmol), Co(BF4)2 (1.2 mg, 0.0035 mmol), D2O (1–2 mL).
Reactions carried out in air. a12 equivalents of oxidant used unless
otherwise specied. bYield and TONs determined by 1H NMR
spectroscopy using 3-(trimethylsilyl) propionic-2,2,3,3-d4 acid sodium
salt as an internal standard. cMass balance ¼ ([recovered starting
material] + [products])/[initial starting material]. dReaction carried out
with RuCl3 as the catalyst, and the product was the N-oxide of the 2-
picolinic acid. eThe substrate was 2-picolinic acid and the product was
the N-oxide of the 2-picolinic acid; 8 equiv. oxidant used. All the
reactions were done in D2O for the ease of characterization of the
species formed by 1H NMR spectroscopy and avoid loss of product
during workup; however, the reaction can be carried in water as the
solvent too.
formed. Since EBS has a reactive benzylic position and an arene
ring deactivated by the sulphonate group, the major oxidation
product was still the ketone, 2.
We next explored the potential of the Co(II)–Oxone system for
the selective oxidative conversion of –Ph groups to –COOH. We
chose 2-phenylpyridine as our substrate for optimization
because of its water solubility and the oxidative resistance of its
protonated pyridine ring, formed in the acidic environment
(typical pH range ¼ 1–2). Our optimization results on its reac-
tion to form 2-picolinic acid are summarized in Table 1. Oxone
was the best oxidant (entries 1–8) among all the other oxidants
tested (entries 9–14). With 12 equiv. versus substrate, we saw
complete oxidation (Fig. S2†). Again, no oxidation took place in
the absence of either Co(II) or Oxone. A catalyst loading of 5
mol% was chosen for further screening (bold entry in Table 1) to
strike a balance between yield and turnover number (TON)
(entries 1–4). The role of temperature was also analyzed (entries
5–8). The rate of the reaction increased considerably on going
from 25 ꢀC to 50 ꢀC (Fig. S4†) without an excessive reduction in
to the overoxidation of the starting material. Besides, variable
amounts of formate and acetate were observed by 1H NMR
spectroscopy in all cases, no doubt due to the oxidation of –Ph
group.
Aer optimizing reaction conditions, we explored the substrate
scope (Table 2). The three positional isomers for phenylpyridine
were each selectively oxidized affording the corresponding
isomeric carboxylic acids in modest yields (entries 1–3). Next, the
functional group oxidation resistance of substituents on the
phenyl ring was tested. Substrates containing both electron-
donating and withdrawing groups (entries 4–7) were transformed
into their carboxylic acid derivatives in similar yields. As expected,
the oxidation-sensitive aldehyde group in 6-(4-uorophenyl)
picolinaldehyde was readily oxidized to the corresponding acid to
yield dipicolinic acid (entry 8). In the case of amino group
substitution (entry 9), total oxidation of both rings resulted in
formate being the only product (1H NMR data). The highly
electron-donating character of the amino group no doubt makes
the substituted pyridine ring much more prone to oxidation. For
2-methylpyridine (entries 10 and 11), the reaction, although slow,
gave the expected oxidation product, 2-picolinic acid, albeit in low
ꢀ
the mass balance and all further screening was done at 50 C.
Since, ruthenium salts6 also catalyze the oxidation of phenyl
rings to carboxylic acids with Oxone, we carried out the same
reaction using RuCl3–Oxone for the sake of comparison. The
reaction was slow and the N-oxide form of the 2-picolinic acid
was obtained as the main product in 27% yield aer 20 h under
otherwise identical conditions, showing the selectivity advan-
tage of the Co(II) system for the title conversion. When 2-pico-
linic acid itself was subjected to the Co(II)–Oxone system, it
exhibited resistance to oxidative degradation (entry 16) with the
N-oxide of the 2-picolinic acid being the only observed product
(yield 60%). The mass balance was around 50% in most of the
cases (Table 1), measured with reference to an internal standard
in a capillary tube; the observation of values <100% is attributed
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Table 2 Screening of substratesa
Entry
Substrate
Product
Time (h)
6
Yielda(%)
38
Mass balance (%)
45
1
2
3
4
5
6
3
3
3
3
4
45
53
38
37
44
51
61
65
37
58
7
8
4
3
43
30
47
30
9
2
3
4
—
10
16
—
69
44
10b
11c
12
2
37
50
a
Reaction conditions: All reactions were carried out in 0.07 mmol scale in D2O at 50 ꢀC with 5 mol% catalyst loading and 12 equivalents of Oxone
unless otherwise mentioned. aYields determined by 1H NMR spectroscopy using 3-(trimethylsilyl) propionic-2,2,3,3-d4 acid sodium salt as an
internal standard. bReaction done at 40 ꢀC with 4 equivalents of Oxone. cReaction done at 70 ꢀC with 8 equivalents of Oxone.
yields even at elevated temperatures and with a higher Oxo-
This observation prompted us to check for similar selec-
ne : substrate ratio. This was surprising because Ar-Me groups are tivity in other cases. Indeed, methyl substituents on the
usually much more easily converted to –COOH groups than is the heteroarene were able to survive the oxidation. With 3-
case for –C6H5 groups, so we have a very unexpected case of easier methyl-2-phenylpyridine, 3-methylpyridine-2-carboxylic acid
oxidation of Ar-C6H5 groups over Ar-Me groups.
was obtained, albeit in low yield (entry 12), again due to the
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selective oxidation of the phenyl ring over the methyl group. electron process, with the preferential oxidation of cyclo-
This constitutes a signicant advantage of the present butanol to cyclobutanone suggesting a predominant two-
method since previous systems using ruthenium8 or potas- electron process. Pyridinium13 ion is known to hinder
sium permanganate9 are known to oxidize aliphatic func- radical mechanisms, by reacting with intermediate carbon-
tionalities either along with (Ru) or in preference to (Mn) based radicals. In our case, however, the outcome of the
phenyl rings.
We have been able to obtain some initial insights into the in the reaction mixture. These results are consistent with a
mechanism. Cobalt ions have been reported previously to two-electron process as the major pathway, where
reaction was not affected by the presence of pyridinium ion
a
interact with Oxone, forming freely diffusing [SO4]cꢁ radicals cobalt oxo species14 might be involved, giving a role to
as the true oxidants.1a,b However, the remarkable selectivity cobalt beyond just activating the Oxone. However, we
reported here towards the phenyl groups intrigued and cannot neglect the possibility of [SO4]cꢁ radicals playing a
motivated us to investigate the mechanism in some detail. In role since we observe to some extent ring opening
principle, the oxidation could proceed through a two- or one- products. The research in this direction is currently
electron process, and both radical10 mechanisms and rst- ongoing and we hope to look at these points in more detail in
row transition metals11 usually prefer the latter. Cyclo- future.
butanol oxidation has been discussed previously as a means
to distinguish between one- and two-electron oxidative
processes.12
Conclusions
It is known from those studies that the strained cyclo-
We report an inexpensive and green protocol for the conversion
of –C6H5 to –COOH groups. This oxidative conversion proceeds
under mild conditions in air and with water as solvent. More-
over, the reaction has a broad substrate scope and is selective
for the oxidation of –C6H5 while leaving untouched aliphatic
substituents on other rings. Yields are only modest but the wide
availability of cheap phenyl derivatives of N-heterocycles could
provide an easy access to their carboxylic acid derivatives. Initial
mechanistic investigations suggest a predominant two-electron
process, where a high valent cobalt oxo species could act as the
true catalytically active species and hence a possible role for the
cobalt ions beyond activating the Oxone.
butanol system easily opens if free radical intermediates are
formed; otherwise the ring remains intact to give cyclo-
butanone, indicating a 2eꢁ oxidation. When cyclobutanol
was treated with Co(II)–Oxone under our conditions, cyclo-
butanone was formed in 80% yield along with other products
(Fig. 2). The peak assignments for the other oxidation prod-
ucts g-butyrolactone, g-hydroxybutyric acid and succinic acid
were conrmed by the addition of authentic samples of these
materials to the NMR solutions. If the published criteria hold
in this case, the reaction would then appear to go through a
mixed pathway involving both a one-electron and a two-
Fig. 2 Conversion of cyclobutanol to cyclobutanone with the Co(II)–Oxone system, demonstrating the oxidation process is predominantly a
two-electron process. Reaction conditions: 5 mol% catalyst, 2 equiv. of Oxone, room temperature for 40 min.
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Experimental
General Procedure for catalytic oxidation
A mixture of Oxone (516 mg, 0.84 mmol), the corresponding
substrate (0.07 mmol) and the cobalt catalyst (1.2 mg, 5 mol%)
were added to a NMR tube with a capillary containing 3-(tri-
methylsilyl) propionic-2,2,3,3-d4 acid sodium salt as the internal
standard and dissolved in deuterium oxide (1–2 mL). Aer
collection of the initial 1H NMR spectra, the NMR tube was
placed in an oil bath preheated to the required temperature.
The reaction was monitored by the 1H NMR spectrum at
different time intervals. In reactions where complete conversion
was too rapid even at room temperature the initial 1H NMR
spectra were taken prior to addition of the cobalt catalyst or by
keeping the NMR tube in an ice bath. The yield was determined
by comparative integration of the product and starting material
peaks to the internal standard in the 1H NMR spectrum.
2-phenyl pyridine was used as a representative substrate, and
the isolated yield of 2-picolinic acid was obtained (see ESI† for
details).15 Product identities in all the cases were determined by
addition of authentic commercially available compounds.
Acknowledgements
The authors acknowledge support from the Chemical Sciences,
Geosciences, and Biosciences Division, Office of Basic Energy
Sciences, Office of Science, U.S. Department of Energy (DE-
FG02-07ER15909). We would like to thank Dr Matthieu Koepf
for his suggestions and discussions.
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