Light-Driven C?H Oxygenation of Methane into Methanol and Formic Acid by Molecular Oxygen Using a Perfluorinated Solvent

Article abstract of DOI:10.1002/anie.201710945

The chlorine dioxide radical (ClO₂^.) was found to act as an efficient oxidizing agent in the aerobic oxygenation of methane to methanol and formic acid under photoirradiation. Photochemical oxygenation of methane occurred in a two-phase system comprising perfluorohexane and water under ambient conditions (298 K, 1 atm). The yields of methanol and formic acid were 14 and 85 %, respectively, with a methane conversion of 99 % without formation of the further oxygenated products such as CO₂ and CO. Ethane was also photochemically converted into ethanol (19 %) and acetic acid (80 %). The methane oxygenation is initiated by the photochemical Cl?O bond cleavage of ClO₂^. to generate Cl^. and O₂. The produced Cl^. reacts with CH₄ to form a methyl radical (CH₃^.). Finally, the oxygenated products such as methanol and formic acid were given by the radical chain reaction. A fluorous solvent plays an important role of inhibiting the deactivation of reactive radical species such as Cl^. and CH₃^..

Full text of DOI:10.1002/anie.201710945

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Accepted Article
Title: Light-driven C-H Oxygenation of Methane into Methanol and
Formic Acid by Molecular Oxygen Using Perfluorinated Solvent
Authors: Kei Ohkubo and Kensaku Hirose
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201710945
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10.1002/anie.201710945
Angewandte Chemie International Edition
COMMUNICATION
Light-driven C-H Oxygenation of Methane into Methanol and
Formic Acid by Molecular Oxygen Using Perfluorinated Solvent
Kei Ohkubo,*[a,b,c] and Kensaku Hirose[c]
•
Abstract: Chlorine dioxide radical (ClO2 ) was found to act as an
efficient oxidizing agent in the aerobic oxygenation of methane to
methanol and formic acid under photoirradiation. Photochemical
oxygenation of methane occurred in a two-phase system comprising
perfluorohexane and water under ambient conditions (298 K, 1 atm).
The yields of methanol and formic acid were 14% and 85%,
respectively, with a methane conversion of 99% without formation of
the further oxygenated products such as CO2 and CO. Ethane was
also photochemically converted into ethanol (19%) and acetic acid
(78%). The methane oxygenation is initiated by the photochemical Cl–
temperature conditions. For examples of recent works, CH4
oxygenation with transition metal catalysts was required to nitrous
oxide (N2O) and hydrogen peroxide (H2O2) as oxidants, which are
both expensive reagents, that were also performed under the
high-pressure and high-temperature conditions.[8–11] Towards that
end, molecular oxygen (O2) is the best oxidant for economical and
environmentally benign oxygenation reactions because of its
abundant availability and nontoxicity.[12] To date, there have been
no reports regarding the aerobic conversion of gaseous CH4 into
liquid oxygenated compounds, such as CH3OH and HCOOH,
under ambient conditions. Thus, direct oxygenation of CH4 to
CH3OH and HCOOH with molecular oxygen remains a formidable
O bond cleavage of ClO2 to generate Cl• and O2. The produced Cl•
reacts with CH4 to form a methyl radical (CH3 ). Finally, the
oxygenated products such as methanol and formic acid were
given by the radical chain reaction. A fluorous solvent plays an
important role of inhibiting the deactivation of reactive radical
•
•
•
challenge. Here we show that chlorine dioxide radical (ClO2 ) acts
as an efficient oxidizing agent in the selective oxygenation of CH4
to MeOH and HCOOH under photoirradiation under ambient
conditions (298 K, 1 atm). Thus, the present study provides an
environmentally benign approach towards the photooxidation of
organic compounds.
species such as Cl• and CH3 .
•
Extensive efforts have been devoted towards the development of
methods for the direct conversion from methane (CH4), ethane
(CH3CH3), or other abundant natural gasses into useful products,
such as the corresponding alcohols, aldehydes, ketones, and
carboxylic acids, as liquid fuels and precursors of chemical and
pharmaceutical products.[1–4] Selective aerobic oxygenation of
CH4 into liquid products without the concomitant formation of CO2
and CO has served as an elusive target reaction. The one-step
transformation of CH4 into methanol (CH3OH) is carried out in
nature using methane monooxygenases.[5–7] However, under
chemical conditions, the selective oxygenation of CH4 to CH3OH
with molecular oxygen (O2) has been unknown because the
oxidation of oxygenated products, CH3OH and formic acid
(HCOOH) are much easier than that of CH4, leading to over-
oxidation products such as CO and CO2.
For the transformation of CH4, the most important initial step
is the activation of the C–H bond via hydrogen abstraction. CH4 is
the most inert hydrocarbon due to the strong C–H s-bonds, which
have a bond dissociation energy of 103 kcal mol–1.[13] Thus, the
activation of CH4 at low temperature requires a strong activator.[14]
It is well-known that chlorine radical (Cl•), generated by the
photoirradiation of Cl2, can cleave the C–H bond of CH4 to form
•
methyl radical (CH3 ). However, CH3Cl is formed via a radical
•
chain reaction in the reaction of CH3 and Cl2 or Cl•. Such highly
reactive radical species, CH3• and Cl•, are often deactivated by
hydrogen abstraction with solvent molecules because the C-H
bond dissociation energies of common hydrocarbon solvents are
generally lower than that of CH4. In contrast, water, which does
•
not react with Cl• and CH3 , is a potential solvent for CH4
oxygenation; however, the solubility of CH4 in water are very low.
A fluorous solvent, perfluorohexane (PFH, n-CF3(CF2)4CF3)
was chosen as an ideal solvent for CH4 oxygenation for the
following reasons. First, PFH is more inert than CH4. It is only
comprised of strong C–F bonds and does not contain any C–H
Syntheses of CH3OH and HCOOH used as general-purpose
bulk chemicals should be carried out under low-cost conditions in
terms of economy. Synthetic gas method for industrial CH3OH
synthesis has been carried out under the high-pressure and high-
•
bonds; therefore, PFH does not react with CH3 and Cl•
intermediates in the oxygenation of CH4. Notably, PFH can
dissolve gaseous substrates such as CH4, CH3CH3, and O2 very
well.[15] Additionally, oxygenated products such as CH3OH and
HCOOH, as well as water, are insoluble in PFH.[16] Thus, if a two-
phase PFH/water system was used for the oxygenation of CH4,
the reaction would occur in the fluorous phase, and the products
would be transferred into the aqueous phase without further
oxygenation to CO and CO2. Towards that end, herein, we report
the two-phase photooxygenation of CH4 by molecular oxygen (O2)
[a]
Prof. Dr. Kei Ohkubo
Institute for Advanced Co-Creation Studies and Institute for
Academic Initiatives, Osaka University,
2-1 Yamada-oka Suita, Osaka 565-0871 (Japan)
E-mail: ohkubo@irdd.osaka-u.ac.jp
Prof. Dr. Kei Ohkubo
dotAqua Inc.,
2-1 Yamada-oka Suita, Osaka 565-0871 (Japan)
Prof. Dr. Kei Ohkubo, Mr. Kensaku Hirose
Department of Material and Life Science, Graduate School of
Engineering, Osaka University
[b]
[c]
•
with chlorine dioxide radical (ClO2 ) in PFH/H2O under ambient
2-1 Yamada-oka, Suita, Osaka, 565-0871, Japan
conditions to produce oxygenated products such as CH3OH and
•
HCOOH, as shown in Scheme 1. ClO2 can be easily prepared
Supporting information for this article is given via a link at the end of
the document.
from sodium chlorite (NaClO2), which is known
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10.1002/anie.201710945
Angewandte Chemie International Edition
COMMUNICATION
CH4
solv.
a 0 min
10
8
6
4
2
0
Chemical Shift / ppm
b 15 min
solv.
HCOOH
Scheme 1. Two-phase photooxidation of CH4 by NaClO2. NaClO2 is dissolved
in an aqueous phase and CH4 is dissolved in fluorous phase, whereas the
oxygenated product, CH3OH and HCOOH are accumulated in an aqueous
phase
CH3OH
CH4
as a stable radical and a non-toxic and inexpensive oxidizing
agent for a number of organic transformations.[17] ClO2• generates
chlorine radical (Cl•) and O2 upon photoexcitation;[18] Cl• can
10
8
6
4
2
0
•
Chemical Shift / ppm
cleave the C-H bond of CH4 to form a methyl radical (CH3 ), and
Figure 1. 1H NMR spectra of the D2O phase a, before and b, after
the subsequent addition of O2 would give oxygenated product.
•
•
A solution of ClO2 was prepared by mixing NaClO2 (200
photochemical reaction of CH4 with ClO2 in D2O/PFH (1:1 v/v) at 298 K
mM) and HCl (200 mM) in an aqueous solution (5 mL) at room
temperature as described in literature as given by Eq. (1).[19,20]
irradiated by a xenon lamp (500 W) through a glass/water filter.
Table 1. Photochemical reaction data for the oxygenation of CH4 and CH3CH3
in a PFH/H2O two-phase solution at 298 K and 1 atm
•
5NaClO2 + 4HCl → 4ClO2 + 5NaCl + 2H2O
(1)
Reaction Conv.,[a]
Product Yield[a]
MCE[b]
c]
F,[
Substrate
The formation of ClO2• was confirmed by UV-vis absorption (lmax
time
[mol/mol]
[%]
[%]
130
•
=358 nm).[19] The oxygenation of CH4 (1.0 mM) with ClO2 (1.0
CH4
15 min
10 min
99
99
CH3OH: 14%
2.1
3.5
mM) did not proceed in the dark. In contrast, the photochemical
oxygenation of CH4 with O2 occurred to form CH3OH and HCOOH
under photoirradiation with a xenon lamp (500 W) in an aqueous
solution at 298 K and 1 atm for 2 h. The yields of CH3OH and
HCOOH: 85%
CH3CH2OH: 19%
CH3COOH: 78%
CH3CH3
400
1
HCOOH were 5% and 25%, respectively, as determined by H
[a] Conversions and yields based on initial concentration of substrate (1.0 mM).
[b]
NMR and gas chromatography-mass (GC-MS) spectroscopies.
Molar conversion efficiency based on initial concentration of NaClO2 (0.10
mM). [c] Determined by the initial rate for formation of the corresponding alcohol
and carboxylic acid.
1
The conversion of CH4 was determined to be 30% by H NMR.
The selectivity of the formation of CH3OH and HCOOH was >99%,
based on the consumption of CH4.
130%, as determined by actinometric measurements using
monochromatized light. When CH4 was replaced with ethane
(CH3CH3), light-driven oxygenation also occurred to yield
CH3CH2OH (19%) and CH3COOH (78%) under the otherwise
same reaction conditions (Figure S1 in the supporting information
Further improvement of the product yield by employing a
two-phase system instead by one-phase aqueous system, a CH4-
saturated solution of PFH (1.0 mL) was added to an oxygen-
saturated aqueous solution containing ClO2• (1.0 mM) to prepare
a two-phase system; oxygenation of CH4 (1.0 mM) in an aqueous
liquid-liquid two-phase solution (1:1 v/v) comprised of PFH and
distilled water was carried out under the same conditions. CH4
dissolved in the aqueous and fluorous phases was completely
consumed following photoirradiation for 15 min. The product
yields of CH3OH and HCOOH were improved to 14% and 85%,
respectively, as determined by the 1H NMR analyses of the
aqueous phase (Figure 1). The consumption of CH4 was
monitored by GC-MS analysis of the fluorous and aqueous
phases. The selectivity of the CH3OH and HCOOH formation was
>99%, based on the initial concentration of CH4. The formation of
further oxygenated products such as CO and CO2, was not
observed under the present reaction conditions.[21] The quantum
yield of the photo-driven CH4 oxygenation was
•
(SI)). The molar conversion efficiencies (MCE = [product]/[ClO2 ]0)
were 2.1 mol/mol for CH4 and 3.5 mol/mol for CH3CH3, as
determined from the consumption of the substrate based on the
•
initial concentration of ClO2 (0.10 mM). The reaction data is
summarized in Table 1. As a reference experiment, the yield of
oxygenated product was significant smaller than the case of
aerobic conditions. This is the first example of the aerobic
oxidation of CH4 and CH3CH3 under ambient conditions (298 K, 1
atm). The enhanced reactivity in the two-phase system comprised
of PFH/D2O as compared to that in the one-phase aqueous
system was ascribed to the stabilization of radical intermediates
in the photoinduced oxygenation reaction, which hampered the
•
hydrogen abstraction of the solvent by Cl• and CH3 . Additionally,
when PFH/D2O was replaced with CDCl3/D2O, the product yield
significantly decreased due to the deactivation of the C-H bond
dissociation
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10.1002/anie.201710945
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COMMUNICATION
100
80
60
MS Intensity
CH316OH
CH318OH
40
20
0
28 30 32 34 36 38 40
1150 1200 1250 1300 1350 1400
m/z
Wavelength, nm
Figure 2. Mass spectra of methanol after the reaction of CH4 with ClO2 in the
presence of O2 (black) and 18-O labelled O2 (18O2, gray) in PFH/D2O (1:1 v/v).
Figure 3. Near-infrared emission spectrum of singlet oxygen generated by the
photoexcitation of ClO2• at 405 nm in deaerated D2O at 298 K.
of CDCl3 by the reactive radical intermediates.
•
possible oxygenation of CH3 . The produced Cl• reacts with CH4
To clarify the oxygen source for the CH4 oxygenation, we
performed gas chromatography-mass spectral (GC-MS) analyses.
The mass peak was mainly observed at m/z = 32 for CH3OH, as
shown in Figure 2. When molecular oxygen (16O2) was replaced
with 18-O labelled oxygen (18O2), the peak shifted to m/z = 34,
corresponding to 18-O labelled methanol (CH318OH). Thus, the
oxygen source was confirmed to be molecular oxygen in the
radical chain process (vide infra). When CH4 was replaced with
deuterated methane, CD4, oxygenation did not occur under the
otherwise same reaction conditions because the C-D bond
cleavage of CD4 by Cl• did not take place. This result was the
consistent with the large kinetic isotope effect (KIE) value for the
chlorination of methane (CH4/CD4) with Cl2 (KIE = 10–19).[22,23]
Based on the aforementioned results, a plausible mechanism for
the oxygenation of CH4 to CH3OH and HCOOH is summarized in
Scheme 2. ClO2• is generated from NaClO2 in the presence of an
acid (HCl). The photoexcitation of ClO2• gives Cl• and O2 via bond
rearrangement from Cl–O–Cl to Cl–O–O.[24] The spin state of O2
generated by the Cl–O bond cleavage of ClO2• was confirmed by
the near-infrared emission spectral measurements under
•
to form a methyl radical (CH3 ) and HCl via C–H bond dissociation.
•
The addition of singlet oxygen to CH3 occurs rapidly to afford
methyl peroxyl radical (CH3OO•). The bimolecular reaction of
CH3OO• gives methoxy radical (CH3O•), which reacts with CH4 to
•
yield CH3OH, and is accompanied by the regeneration of CH3 .
The oxygen source for CH3OO• may be singlet oxygen rather than
•
the ground state of O2 in the first radical chain cycle, because CH3
and singlet oxygen are located in the same solvent cage after the
C–H bond cleavage of CH4 by Cl•. The rearrangement from CH3O•
to CH2(OH)• also occurs in competition with the reaction with CH4.
The second radical chain reaction with O2 and CH4 via
CH2(OH)OO• to produce methyl hydroperoxide (CH3OOH) is
accompanied by the regeneration of CH2(OH)•. Finally, CH3OOH
decomposes to formic acid. The chain reactions are terminated
by the disproportionation of CH3OO• to yield CH3OH and
formaldehyde (HCHO). No formaldehyde was observed as a
product, because formaldehyde is promptly oxidized to formic
acid by autoxidation or Pinnick oxidation.[26,27]
To clarify the reason why the product yield of HCOOH was
larger than that of CH3OH (Figure 1 and Table 1), density
functional theory (DFT) calculations were carried out by using the
M06-2X/6-311+G(d,p) level of theory (see the experimental
section in SI). The ratio of the product yields may be controlled by
the difference in the autocatalytic reactivity of cycle A and B which
were mediated in the rearrangement reaction of CH3O• to
CH2(OH)• and hydrogen transfer from CH4 to CH3O• (Scheme 2).
•
photoirradiation of ClO2 in D2O as shown in Figure 3. The
emission band at 1270 nm detected was assigned to singlet
oxygen (1Dg).[25] It is known that singlet oxygen has a much higher
reactivity than the ground state of O2 (triplet, 3Sg ) to make
–
HCOOH
O2
CH3OO•
x2
– (1/2)O2
+ [O]
The energy difference (DE) of the rearrangement, CH3O•
→
hν
•
•
A
Cl•
CH4
CH3
CH2(OH)• bound for the radical chain cycle of HCOOH formation,
is determined to be negative (–3.6 kcal mol–1) obtained by DFT
calculations. In contrast, the DE value for the CH3OH formation,
CH3O• + CH4 → CH3• + CH3OH, is slightly positive (+1.3 kcal mol–
CH3OH + HCHO + O2
ClO2
HCl
CH3OH
O2
acid
NaClO2
CH3O•
O2
CH2(OH)•
CH3OOH
CH4
B
H2O
CH2(OH)OO•
CH4
1). However, the following reaction, CH3 + O2 → CH3OO•, is
•
HCHO
exothermic (DE = –36.8 kcal mol–1). The total stoichiometry,
CH3O• + CH4 + O2 → CH3OH + CH3OO• for the initial step of the
radical chain process, is energetically favourable (DE = –35.4 kcal
mol–1).
x2
+ [O]
HCOOH + HCHO + H2O + O2
HCOOH
Scheme 2. Plausible reaction mechanism for oxygenation of CH4 into CH3OH
•
and formic acid with ClO2 . hn means photoirradiation. [O] means autooxidation.
In conclusion, in this preliminary study, we found that
chlorine dioxide radical can act as an efficient reagent for the one-
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COMMUNICATION
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photochemical oxygenation using ClO2• reported herein could be
generalized to provide novel chemical reactions, which may have
significant implications in synthetic and pharmaceutical chemistry.
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Acknowledgements
Authors deeply thank Prof. Shunichi Fukuzumi (Ewha Womans
University, Korea and Meijo University Japan) Prof. Tsuyoshi
Inoue and Prof. Hiroaki Adachi (Osaka University, Japan) for the
useful discussion and suggestions. This work was supported by
Grants-in-Aid (no. 17H03010, 16K13964, 26620154 and
26288037) from the Ministry of Education, Culture, Sports,
Science and Technology (MEXT), New Energy and Industrial
Technology Development Organization (NEDO) and Acenet Inc.
Collaborative Foundation.
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Org. Chem. 2017, 30, e3619.
Keywords: photochemistry • oxygenation • chlorine dioxide • C-
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[6]
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10.1002/anie.201710945
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COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
•
Chlorine dioxide radical (ClO2 )
Kei Ohkubo* and Kensaku Hirose
was found to act as an efficient
oxidizing agent in the aerobic
oxygenation of methane to
methanol and formic acid under
photoirradiation. The yields of
methanol and formic acid were
14% and 85%, respectively, with a
methane conversion of 99% under
ambient conditions (298 K, 1 atm)
in a two-phase system comprising
perfluorohexane and water.
Page No. – Page No.
Light-driven C-H Oxygenation of
Methane into Methanol and
Formic Acid by Molecular
Oxygen Using Perfluorinated
Solvent
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