Functional Group-Directed Photochemical Reactions of Aromatic Alcohols, Amines, and Thiols Triggered by Excited-State Hydrogen Detachment: Additive-free Oligomerization, Disulfidation, and C(sp2)-H Carboxylation with CO2

Article abstract of DOI:10.1021/acs.joc.0c02456

Exploring new types of photochemical reactions is of great interest in the field of synthetic chemistry. Although excited-state hydrogen detachment (ESHD) represents a promising prospective template for additive-free photochemical reactions, applications of ESHD in a synthetic context remains scarce. Herein, we demonstrate the expansion of this photochemical reaction toward oligomerization, disulfidation, and regioselective C(sp2)-H carboxylation of aromatic alcohols, thiols, and amines. In the absence of any radical initiators in tetrahydrofuran upon irradiation with UV light (λ = 280 or 300 nm) under an atmosphere of N2 or CO2, thiols and catechol afforded disulfides and oligomers, respectively, as main products. Especially, the photochemical disulfidation proceeded highly selectively with the NMR and quantum yields of up to 69 and 0.46%, respectively. In stark contrast, the photolysis of phenylenediamines and aminophenols results in photocarboxylation in the presence of CO2 (1 atm). p-Aminophenol was quantitatively carboxylated by photolysis for 17 h with a quantum yield of 0.45%. Furthermore, the photocarboxylation of phenylenediamines and aminophenols proceeds in a highly selective fashion on the aromatic C(sp2)-H bond next to a functional group, which is directed by the site-selective ESHD of the functional groups for the formation of aminyl and hydroxyl radicals.

Full text of DOI:10.1021/acs.joc.0c02456

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Article
Functional Group-Directed Photochemical Reactions of Aromatic
Alcohols, Amines, and Thiols Triggered by Excited-State Hydrogen
Detachment: Additive-free Oligomerization, Disulfidation, and
C(sp2)−H Carboxylation with CO2
Kanae Abe,§ Akinobu Nakada,§ Takeshi Matsumoto, Daiki Uchijyo, Hirotoshi Mori,
and Ho-Chol Chang*
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ABSTRACT: Exploring new types of photochemical reactions is
of great interest in the field of synthetic chemistry. Although
excited-state hydrogen detachment (ESHD) represents a promis-
ing prospective template for additive-free photochemical reactions,
applications of ESHD in a synthetic context remains scarce.
Herein, we demonstrate the expansion of this photochemical
reaction toward oligomerization, disulfidation, and regioselective
C(sp2)−H carboxylation of aromatic alcohols, thiols, and amines.
In the absence of any radical initiators in tetrahydrofuran upon
irradiation with UV light (λ = 280 or 300 nm) under an
atmosphere of N2 or CO2, thiols and catechol afforded disulfides
and oligomers, respectively, as main products. Especially, the
photochemical disulfidation proceeded highly selectively with the
NMR and quantum yields of up to 69 and 0.46%, respectively. In stark contrast, the photolysis of phenylenediamines and
aminophenols results in photocarboxylation in the presence of CO2 (1 atm). p-Aminophenol was quantitatively carboxylated by
photolysis for 17 h with a quantum yield of 0.45%. Furthermore, the photocarboxylation of phenylenediamines and aminophenols
proceeds in a highly selective fashion on the aromatic C(sp2)−H bond next to a functional group, which is directed by the site-
selective ESHD of the functional groups for the formation of aminyl and hydroxyl radicals.
carboxylation reactions can be classified into four types: (a)
addition reactions of CO2 onto double or triple C−C bonds,
exemplified by Tazuke’s report (Scheme 1a),11,20−27 (b)
carboxylation of alkenes in the presence of a photosensitizer
(Scheme 1b),28,29 (c) carboxylation of C−X (X = halogen or
OTf) bonds (Scheme 1c),30−34 and (d) direct C(sp3)−H
activation with CO2 (Scheme 1d).35−38 Although direct C−H
activation is a more atom- and step-economic approach than
C−X activation,12 the direct photocarboxylation of aromatic
C(sp2)−H bonds has not been reported yet to the best of our
knowledge. In addition, precious metal-based catalysts,
sacrificial reagents, and/or preactivated substrates are neces-
sary for most of the aforementioned photochemical carbox-
ylation reactions using CO2.11,19−38 Hence, further exploring
INTRODUCTION
■
Molecular conversion by using light energy represents a major
challenge in the context of energy- and atom-economic
chemical synthesis.1,2 For instance, the conversion of the
attractive C1 feedstock carbon dioxide (CO2) into benzoic
acid derivatives3−5 and carbonate,6,7 which are important
precursors for the synthesis of pharmaceuticals so far, relies on
the reaction between CO2 and activated aryl halides8,9 or alkali
phenoxide (Kolbe−Schmitt reaction).10 However, these
reactions generally require high temperatures and/or pressure,
as well as strong bases and suffer from the inevitable
production of waste.8−10
In 1975, Tazuke and Ozawa reported the first photo-
chemical carboxylation of aromatics using CO2 at room
temperature.11 In this reaction, the photoreduction of
phenanthrene by amines under irradiation with UV light (λ
= 365 nm) induces the addition of CO2 to phenanthrene to
generate 9,10-dehydrophenanthrene-9-carboxylic acid. Since
the discovery of redox photocatalysis,2 several light-driven
CO2-fixation reactions onto carboxylic acid derivatives have
been reported.12−19 The previously reported photochemical
Received: October 16, 2020
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Scheme 1. (a−d) Previously Reported and (e) Present Photochemical Carboxylation Using CO2
Scheme 2. Plausible Mechanism for the Photoinduced Direct Carboxylation via the ESHD of o-Phenylenediamine (opda)49
potential photochemical reactions is strongly desirable,
especially with a view to their versatile synthetic application.
The excited-state hydrogen detachment (ESHD) of simple
aromatics represents a promising prospective process for the
photochemical activation of E−H bonds (E = O, S, and
N).39,40 Specific E−H bonds of aromatic alcohols,41−43
thiols,41,44,45 and amines46−48 have been reported to dissociate
via π−π* excitation, followed by internal conversion to the
π−σ* state at the conical intersection, which results in
formation of radical species such as the hydrogen radical. If
the generated radical species could be employed for the
formation of new bonds, radical initiator-free photochemical
synthetic routes would be accessible. Although the ESHD
processes themselves have widely been studied by means of
spectroscopies and theoretical calculations in the gas phase39
and even in solution,40 the number of examples where such
ESHD processes of these aromatic compounds have been
applied for synthetic purposes in solution at room temperature
remains scarce.
We have recently reported that the photochemical aromatic
C(sp2)−H carboxylation of o-phenylenediamine (opda) under
atmospheric pressure of CO2 in tetrahydrofuran (THF) affords
the corresponding carboxylic acid, for example, 2,3-diamino-
benzoic acid (Scheme 1e).49 In the presence of Fe(II),
synthetic and quantum yield values of 58 and 0.47%,
respectively, were obtained, while 28 and 0.22% were observed
for opda alone. The proposed reaction mechanism of the
photocarboxylation in the present study is different from that
of the aforementioned photochemical reactions (Scheme 1a−
d): a hydrogen radical-trapping experiment for opda strongly
suggested that the ESHD from an amino N−H bond initiates
the carboxylation of aromatic C−H bonds via the migration of
the radical in the aminyl radical species (Scheme 2).49 It
should be noted here that this direct photocarboxylation does
not require any potentially reactive sacrificial reagents,
preactivated substrates, or strong bases (Scheme 1e). Although
the concept of photochemical reactions based on ESHD can be
expected to expand the scope with regard to synthetic
chemistry by utilizing light energy, the photochemical
reactivity has so far been documented only for carboxylation
of phenylenediamines.49 Against this background, we have
unveiled the photochemical reactivity of other organic
substrates (Figure 1), with the aim to develop diverse
applications for ESHD in photochemical synthesis.
Herein, we report substituent effects of aromatic compounds
with hydroxyl, amino, and thiol groups, including monosub-
stituted (aniline, phenol, and thiophenol) and disubstituted
aromatics, such as catechol (o-bdH2), resorcinol (m-bdH2),
hydroquinone (p-bdH2), o-aminothiophenol (atpH2), o-
aminophenol (o-apH2), m-aminophenol (m-apH2), and p-
aminophenol (p-apH2), on their photoreactivity in the
presence of CO2. The present study highlights the distinctly
unique reactivity of these compounds, that is, their reactivity
depends on the number, position, and combination of
substituents. Specifically, these compounds engage not only
in carboxylation (Scheme 1e) but also in oligomerization and
Figure 1. Aromatic compounds with hydroxyl, amino, and thiol
groups used in this study.
B
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disulfidation. Spectroscopic analyses of the photoreactions
coupled with theoretical calculations have provided guidelines
for the selective photochemical carboxylation with CO2 and
disulfidation.
for the π−π* transitions (HOMO−LUMO and HOMO−
LUMO+1; Figure S2 and Table S2). Importantly, the lowest
π−π* transitions are found between 270 and 315 nm for all
compounds used in this study, which showed luminescence
upon π−π* excitation, albeit that the luminescence intensities
were relatively low for phenol and thiophenol (Figure S3).
Hence, the photoirradiation at 280 or 300 nm used in the
following experiments is able to induce π−π* transitions of the
aromatic compounds.
RESULTS AND DISCUSSION
■
Photophysical Properties of Substituted Aromatic
Compounds under N2 and CO2. Figures 2 and S1 show the
UV−vis absorption spectra of aniline, phenol, thiophenol,
opda, o-bdH2, atpH2, o-apH2, m-apH2, and p-apH2 under an
atmosphere of CO2 or N2. All compounds exhibited two
characteristic absorption bands between 200 and 400 nm, and
peaks in the visible region were not observed. The absorption
spectra are consistent, regardless of the atmospheres (CO2 or
N2), which suggests negligible interactions between the
substrates and CO2 in the ground state. Density functional
theory (DFT) calculations were carried out to assign the
observed absorption bands, which indicated that the HOMO,
LUMO, and LUMO+1 exhibit a π character that arises from
the aromatic rings including heteroatomic substituents,
whereas the LUMO+2 is located around the E−H (E = N,
O, and S) σ-bond(s) for all compounds (Figure S2).
Accordingly, the experimentally observed absorption bands
shown in Figures 2 and S1 were attributed to two distinct
π−π* transitions.
Photochemical Reactivity of Monosubstituted Aro-
matic Compounds under N2 and CO2. Initially, we
attempted the photochemical reactions of monosubstituted
aromatic compounds with amino, hydroxyl, and thiol groups.
According to our previous report,49 aniline showed hardly any
reactivity after photoirradiation at λex = 300 10 nm for 8 h
under N2 or CO2, and the starting materials were recovered in
98 and 96%, respectively (Figure S4 and run 1 in Table 1). On
the other hand, the π−π* absorption band of phenol
broadened after photoirradiation (λex = 280 10 nm) under
1
both N2 and CO2 (Figure S5a). The H NMR spectrum after
photoirradiation revealed phenol as the major species together
with multiple signals in the high-magnetic field region,
regardless of the presence of CO2 (Figure S5b−d). Although
72% of the introduced phenol was consumed, which was
estimated based on the integral ratio of 1H NMR signals using
1
dimethyl sulfoxide (DMSO) as an internal standard, the H
The wavelengths of the absorption maxima of the two π−π*
absorption bands vary depending on the types and positions of
the substituents (Table S1). The spectra of the monosub-
stituted compounds phenol and thiophenol exhibit similar
absorption maxima, while the absorption maximum of aniline
is bathochromically shifted approximately by 20 nm. The
aminophenols exhibit absorption maxima that are shifted by
16−39 nm bathochromically relative to that of phenol, whereas
the shift in the case of o-bdH2 relative to phenol was much
smaller (5 nm). A similar trend was observed for thiophenol
and aminothiophenol. These results suggest that the amino
group tends to red-shift the π−π* absorption. The absorption
maxima of o- and m-apH2 (∼292 nm) are shifted by ca. 20 nm
hypsochromically to that of p-apH2. A similar trend has been
observed for the regioisomers of phenylenediamine49 and
ascribed to the degree of solvent effects, which is different for
each regioisomer.50 The observed shifts in the experimental
absorption bands are comparable to the calculated energy gaps
NMR signals of the products were relatively low, indicating an
unselective formation of multiple products. In fact, an
electrospray ionization (ESI) mass spectrum of the solution
after photoirradiation for 8 h under N2 showed multiple signals
that were attributed to oligomeric phenol-based products
(Figure S5e). Although the mass spectrum of the products
under CO2 showed the parent peak at m/z 137 and 275, which
is consistent with [phenol + CO2−H+]− and [2 phenol + 2
CO2−H+]−, respectively (Figure S5f), these species were not
1
prominent in the H NMR spectrum (Figure S5d). Based on
these results, we concluded that phenol is photoreactive but
gives trace amounts of CO2 adducts and oligomers (run 2 in
Table 1).
In the case of thiophenol, a new strong absorption band
emerged in the UV region after photoirradiation (λex = 280
10 nm) for 8 h, regardless of the atmosphere (Figure 3a). The
1H NMR spectrum of the photochemical products under N2
atmosphere showed that the main signals were assignable to
1
diphenyl disulfide (DPD) (Figure 3b−d). The H NMR yield
and quantum yield (Φ) of DPD were estimated to be 52 and
0.37%, respectively, based on the amount of thiophenol used
(run 3 in Table 1). The photochemical coupling of thiols to
afford a disulfide has already been reported, albeit that a
photocatalyst that acts as a photochemical radical initiator is
required.51−55 To the best of our knowledge, this is the first
example of a direct photochemical disulfidation of thiophenol
in the absence of any additives. In the presence of CO2, the
same photoreactivity was observed as under N2 (Figures 3a
and S6), indicating that thiophenol selectively engages in
disulfidation rather than reacting with CO2 upon photo-
irradiation.
As mentioned above, the monosubstituted aromatic
compounds showed distinct photoreactions upon π−π*
excitation in THF, depending on the functional groups (runs
1−3 in Table 1). According to previous studies on the ESHD
of these aromatic compounds, the homolytic cleavage of the
E−H bonds (E = N, O, or S) of these compounds via π−π*
Figure 2. UV−vis spectra of THF solutions (6.0 mM) of aniline (light
blue), phenol (light green), thiophenol (orange), opda (blue), o-bdH2
(green), atpH2 (brown), o-apH2 (red), m-apH2 (black), and p-apH2
(purple) immediately after preparation of each solution under CO2 at
room temperature.
C
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Table 1. Photochemical Products of Substituted Aromatics under CO2
a
b
c
d
1H NMR yield (%). External quantum yield (%). Reference 49. N.D. = not detected.
excitation and subsequent π*/σ* internal conversion at a
conical intersection is possible even in solution.40 Hence, the
ESHD efficiency should be one of the determining factors for
the photochemical reactivity of these aromatic compounds. It
has been reported that phenol41,43 and thiophenol41,44 show
E−H bond cleavage, whereas the π−π* excitation of aniline
does not induce N−H bond cleavage in the gas phase on
account of the high activation energy in the π*/σ* conical
intersection.47 The lack of photoreactivity of aniline in THF
(Figure S4 and run 1 in Table 1) is consistent with the
aforementioned trend observed for the ESHD in the gas phase.
Furthermore, a photochemically generated radical counterpart
after ESHD would delocalize over the E atom (E•) to the
aromatic carbons (Ph•), as depicted in Scheme S1, which
would promote oligomerization (E = O) and dimerization (E
= S) via intermolecular E•/Ph• and E•/E• coupling,
respectively. Whereas phenol furnished multiple products
including oligomers and byproducts that could not be assigned,
thiophenol engaged efficiently in disulfidation. These results
can be, at least in part, rationalized in terms of the larger
atomic radius of sulfur relative to oxygen and nitrogen, which
leads to weak electronic interactions between the S 3p and the
aromatic π orbitals, as reported by Ashfold et al.41
Consequently, a counterpart radical generated via ESHD
D
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remained unreacted (Figure S8b−d). ESI mass spectra showed
several peaks associated with o-bdH2, oligomers, and THF-
incorporated compounds (Figure S8e−g). Considering that
similar photoreactivity was observed both under both N2 and
CO2 without any evidence for CO2 incorporation, it seems
feasible to conclude that o-bdH2 does not react with CO2 upon
photoirradiation. Photolysis of the regioisomers (m-bdH2 and
p-bdH2) also gave oligomers (Figures S9 and S10, runs 6 and 7
in Table 1). Although the reaction of o-bdH2 with THF is
characteristic, o-bdH2 (run 5 in Table 1) shows a behavior that
is essentially comparable to that of phenol (run 2), while it is
distinctly different from that of opda,49 which engages in
photocarboxylation (run 4).
Disubstituted aromatics with two different substituents were
also investigated with respect to their photoreactivity. In the
case of atpH2, we observed that the formation of disulfides is
favorable even in the presence of CO2 (Figure S11), similar to
1
the case of thiophenol (Figure 3). The H NMR yield and
quantum yield (Φ) of bis-2-aminophenyl-disulfide were
estimated to be 69 and 0.46%, respectively (run 8 in Table
1). As discussed for the photoreactivity of thiophenol, the
relatively high S−S bond energy and localization of the radical
on the sulfur atom likely causes the preferred formation of the
S−S bond relative to the carboxylation, even in the presence of
an amino group.
In contrast, o-apH2 showed drastic changes of its absorption
spectrum upon photoirradiation (λex = 300 10 nm), when
under a N2 or CO2 atmospheres (Figure 4a). As opposed to
the initial absorption maximum at 292 nm, which is
attributable to the π−π* transition, the photolysis of o-apH2
induced a broadening of the π−π* absorption under N2.
Conversely, a new characteristic absorption band emerged at
λmax = 341 nm under a concomitant decrease of the original
π−π* absorption at λmax = 292 nm after photolysis in the
presence of CO2, which strongly suggests a progressing
Figure 3. (a) UV−vis absorption spectra of thiophenol in THF (6.0
mM) before irradiation under N2 (black dashed line) or CO2 (blue)
and after irradiation at λex = 280 10 nm for 8 h under N2 (green) or
CO2 (red) at room temperature (the black and blue lines overlap each
other). 1H NMR (CDCl3, 400 MHz) spectra of thiophenol (b) before
and (c) after the photoirradiation for 8 h and (d) commercial DPD at
room temperature under a N2 atmosphere. The symbols “#”, “*”, and
“‡” indicate the signals from residual protons of H2O, CHCl3, and
THF, respectively. The full 1H NMR spectra are shown in Figure S6.
1
photochemical reaction that involves CO2 fixation. The H
NMR spectrum of the photochemical product is substantially
different from that of o-apH2 (Figure 4b) but corresponds to
that of 3-amino-2-hydroxybenzoic acid (3A2H) (Figure 4c,d).
The carboxylation of o-apH2 was further supported by the
negative ESI mass signal of the product at m/z 152, which
predominantly localizes on the E atom only in the case of
thiophenol (E = S) but not in the case of aniline (E = NH) and
phenol (E = O); the preferable coupling of thiyl radicals is also
supported by the results of spin density calculations (Figure
S7). Moreover, the S−S bond energy (264 kJ mol−1) is higher
than that of O−O (146 kJ mol−1),56 which makes the disulfide
bond substantially more stable than the peroxide bond.
Photochemical Reactivity of Disubstituted Aromatic
Compounds under N2 and CO2. In contrast to mono-
substituted aromatics, that is, aniline, phenol, and thiophenol,
which exhibit limited photoreactivity toward carboxylation, our
previous study demonstrated the successful photocarboxylation
of opda with CO2 (run 4 in Table 1).49 Furthermore, Pino et
al. have reported that the introduced amino group in o-apH2
drastically enhances the mixing of the π*/σ* excited states
compared to phenol, leading to efficient ESHD.48 These facts
motivated us to investigate the effects of the presence of a
second functional group in such aromatic compounds on their
photoreactivity toward carboxylation.
1
corresponds to [o-apH2 + CO2−H+]− (Figure 4e,f). The H
NMR yield and quantum yield (Φ) of 3A2H were calculated to
be 25 and 0.34%, respectively (run 9 in Table 1). Conversely,
1
the H NMR signals assignable to other regioisomers, for
example, 2-amino-3-hydroxybenzoic acid (2A3H) (Figure
S13a), 3-amino-4-hydroxybenzoic acid (3A4H) (Figure
S13b), or 4-amino-3-hydroxybenzoic acid (4A3H) (Figure
S13c) were not obtained in detectable amounts. Hence, we can
conclude that the photoirradiation of o-apH2 under CO2 leads
to regioselective carboxylation of the C(sp2)−H bond that is
ortho position-relative to the hydroxy group. Notably, the
photocarboxylation reaction does not require any electron
donors or bases; the photoreactivity of o-apH2 became
negligible when the base TBAOH was added to the reaction
solution (Figure S14). Therefore, the present photochemical
reaction is characteristically distinct from previously reported
conventional photocarboxylation reactions.11−38
In the case of o-bdH2, which contains two hydroxy groups at
the o-position relative to each other, photoirradiation (λex
=
280 10 nm) for 8 h led to a slight decrease of the absorption
band at 278 nm coupled with a growth of a broad absorption
in the UV region under both N2 and CO2 (Figure S8a). In the
1H NMR spectrum after photoirradiation under both N2 and
CO2, several new signals were observed, which suggested the
formation of multiple products, while ca. 30% of o-bdH2
Effects of Functional Groups on the Selectivity of the
Photocarboxylation. Notably, o-apH2 shows photocarbox-
ylation selectively on the aromatic carbon next to the hydroxy
group (run 9 in Table 1), while an orthoselective carboxylation
relative to the amino group occurs in opda,49 indicating that
E
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the ortho position relative to the hydroxy group initiates the
carboxylation. This hypothesis is supported by the fact that o-
anisidine, which contains a methoxy instead of a hydroxy
group, did not afford any carboxylation product because of the
absence of an O−H bond (Figure S15). The calculated
molecular orbitals of o-apH2 in THF indicates that the lowest-
lying σ* excited state is localized at the O−H bond (Figure
S2g), which is consistent with the DFT calculations on o-apH2
reported by Pino et al.48 Therefore, the O−H bond
preferentially dissociates via π−π* photoexcitation, followed
by π*/σ* conical intersection, leading to a selective
carboxylation at the ortho position relative to the hydroxy
group rather than that relative to the amino group.
Effects of the Substituent Positions of Aminophenols
on the Photocarboxylation. As described above, amino
substitution of phenol at the ortho position allows photo-
carboxylation, although the amino group does not function as
the source of radicals, which strongly suggests that the amino
group acts as a supporting moiety. Thus, we further
investigated the photochemical reactivity of the two
regioisomers, m- and p-apH2. UV−vis absorption spectra
1
(Figure 5a), together with H NMR (Figure 5b−e) and ESI
mass spectra (ESI-MS) (Figure 5f,g) spectroscopic studies on
the photochemical products obtained from p-apH2 revealed
that the photocarboxylation proceeds selectively on the C−H
bond next to the hydroxy group to form 5-amino-2-
hydroxybenzoic acid (5A2H), similar to the case of o-apH2.
The synthetic yield and Φ were 34 and 0.45%, respectively
(run 10 in Table 1). Furthermore, the signals of the aromatic
protons derived from p-apH2 were fully converted to 5A2H
after 17 h of photoirradiation (Figure 5d). On the other hand,
m-apH2 did not show any significant changes in the UV−vis
1
absorption and H NMR spectra after photoirradiation under
CO2 (Figure S16), which demonstrates considerable inertness
toward photochemical reactions (run 11 in Table 1).
The efficiency of the ESHD should be one of the main
factors to determine the photoreactivity for the carboxylation.
Using resonantly enhanced multiphoton ionization spectros-
copy in the gas phase, Fujii and Dedonder-Lardeux et al. have
demonstrated that m-fluorophenol exhibits an excited-state
hydrogen transfer (ESHT) to ammonia that is slow compared
to that of o- and p-fluorophenol.57 In this previous report, the
position of the fluorine substituent was proposed to affect the
energy of the π−σ* state and thus the rate of the ESHT via the
π*/σ* conical intersection. A similar explanation may also
apply to the case of aminophenols; the activation energies from
the optimum structure of the S1(π−π*) state to the S1(π−π*)/
(π−σ*) conical intersection points are shown in Table 2. Both
TDDFT and ab initio CASPT2 calculations clearly show that
m-apH2 requires a higher activation energy than o- and p-apH2.
These results suggest that the efficiency of the ESHD should
be much lower for m-apH2, which is commensurate with
negligible activity for photocarboxylation.
The stability of the generated radical species should also be
considered as another factor in the determination of the
photocarboxylation reactivity. The radical resonance structures
of o- and p-apH2 include tertiary carbon radicals bound to the
amino groups, while those of m-apH2 do not (Scheme 4). As
tertiary carbon radicals are known to be more stable than
secondary carbon radicals,58 radical intermediates of o- and p-
apH2 may be more likely to react with CO2.
Figure 4. (a) UV−vis spectra of o-apH2 in THF (6.0 mM) before
irradiation under N2 (black dashed line) or CO2 (blue) and after
irradiation at λex = 300 10 nm for 8 h under N2 (green) or CO2
(red) at room temperature (the black and blue lines overlap each
1
other). H NMR (CD3OD, 400 MHz) spectra of o-apH2 (b) before
and (c) after the photoirradiation for 8 h, and of (d) commercial
3A2H at room temperature under a CO2 atmosphere. The symbols
“#”, “*”, and “‡” indicate the signals from residual protons of H2O,
1
CD2HOD, and THF. The full H NMR spectra are shown in Figure
S12. (e,f) Negative ESI-MS spectrum of the reaction solution of o-
apH2 (e) before and (f) after photoirradiation for 8 h under a CO2
atmosphere.
ortho-hydroxycarboxylic acid and -aminocarboxylic acid
moieties can be generated from o-apH2 and opda, respectively.
The origin of the selectivity of the photocarboxylation can be
interpreted in terms of a functional group-directed ESHD. As
described above, both opda46 and o-apH248 have been reported
to engage in ESHD in the gas phase. According to their radical
resonance structures, a radical generated by ESHD on the E
atom (E•) can migrate to its ortho and para positions (Scheme
S1). In the case of o-apH2, a photodissociation of the O−H
bond is necessary for the formation of 3A2H (Scheme 3),
assuming that a radical reaction between CO2 and a radical at
F
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Scheme 3. Photochemical Carboxylation of o-ApH2 via an ESHD Processes Involving (a) O−H or (b) N−H Bond Dissociation
degassed by at least five freeze-pump−thaw cycles and sparging with
N2 or CO2 gas for 20 min prior to use.
CONCLUSIONS
■
In this study, we investigated the substituent effects of
hydroxyl, thiol, and amino groups on the photocarboxylation
reactivity of aromatic compounds in the absence and presence
of CO2. We found that the functional groups direct the
selectivity of the photochemical reaction; phenols and
thiophenols engage in oligomerization and disulfidation even
in the absence of any radical initiator, whereas o-phenylenedi-
amine (opda) and o-aminophenol (o-apH2) engage in the
direct photocarboxylation with CO2 in the absence of any
additives. Because of the characteristic localization of the
lowest-lying σ* orbitals, it was possible to construct o-
aminobenzoic acid and o-hydroxybenzoic acid moieties from
opda and o-apH2, respectively. Moreover, we found that the
position of the amino group also influences the photoreactivity
of aminophenols and that o-/p-apH2 are suitable for photo-
carboxylation reactions with CO2, which is supported by the
results of theoretical calculations. The photoirradiation of p-
apH2 leads to a complete carboxylation within 17 h with a
quantum yield (Φ) of 0.45% at room temperature, suggesting
sufficient potential to serve in the photochemical synthesis of
aromatic carboxylic acids.
The findings of the present study suggest promising
potential of ESHD in synthetic applications, even in the
absence of any additives such as radical initiators, bases, or
reductants/oxidants. In particular, the activation of the
aromatic C−H bond generally requires higher energy than
that of aliphatic C(sp3)−H bonds, and consequently, aliphatic
C(sp3)−H bonds are preferentially activated relative to
aromatic C(sp2)−H bonds by conventional photochemical
hydrogen atom transfer systems.59,60 On the other hand, the
present study enables the selective carboxylation of aromatic
C(sp2)−H bonds via the ESHD of E−H bonds (E = NH and
O). This photochemical reaction based on ESHD can thus be
expected to provide new options for the photochemical
synthesis of useful aromatics with CO2.
Physical Measurements. UV−vis absorption and emission
spectra were recorded at room temperature on a Hitachi U-4100
and a Horiba FluoroMax-4 spectrophotometer, respectively. 1H NMR
spectra were measured on Varian 400 MHz and JEOL ECA-500
spectrometers (400 and 500 MHz). ESI-MS were recorded on a
Shimadzu LCMS-2020 liquid chromatograph mass spectrometer.
Photochemical Reactions. Sample solutions were prepared
under an atmosphere of N2 or CO2. Degassed THF solutions (6.0
× 10−3 M, 4.0 mL) of phenol, thiophenol, o-bdH2, atpH2, o-apH2, m-
apH2, or p-apH2 were placed into a handmade quartz tube (headspace
= 165 mL) equipped with a Schlenk flask, which was preliminarily
filled with N2 or CO2 at ambient pressure by vacuum−refill cycles.
The THF solutions were irradiated for 8 h using a Hg−Xe lamp (LC-
8, Hamamatsu Photonics K.K.). The photoirradiation wavelength was
fixed by using LX0280 (Asahi Spectra Inc., λ = 280 10 nm, half
bandwidth: 10.8 nm) or LX0300 (Asahi Spectra Inc., λ = 300 10
nm, half bandwidth: 10.4 nm) band-pass filters. The light intensity,
which was measured before each experiment using a power meter
(Nova, Ophir Optronics Ltd.) and a thermopile sensor (3A, Ophir
Optronics Ltd.), was set to 24.8−29.3 mW. During photoirradiation,
H2 generated in the headspace was collected using a gas-tight syringe
(Tokyo Glass Kikai Co. Ltd) and analyzed on a gas chromatograph
(GC-2014, Shimadzu) equipped with a thermal conductivity detector
and molecular sieve 5A column (3.0 m) with Ar as the carrier gas
(15.0 mL/min). The temperatures of column, injector, and detector
were set to 70, 100, and 200 °C, respectively.
A portion of the reaction solution (0.3 mL) was transferred to a
quartz cell (thickness: 1 mm) in order to measure the UV−vis
absorption spectra for analysis of the products in solution after
photoirradiation. The remaining solution (3.7 mL) was transferred to
a Schlenk flask, where the volatiles were removed under reduced
pressure. The thus-obtained residue was analyzed by 1H NMR
spectroscopy, whereby the chemical shifts were corrected using the
employed solvent as an internal standard (CD2HOD in CD3OD: 3.31
ppm; CHCl3 in CDCl3: 7.26 ppm). The intensity of each peak was
calibrated by integration of DMSO added to the solution (2.4 × 10−2
1
M) to evaluate H NMR yields.
The external quantum yield (Φ) for each product was calculated
using eq 1
EXPERIMENTAL SECTION
Φ = Nproducts/Np
■
(1)
General Procedures. All experimental operations were performed
under an atmosphere of N2 or CO2 using standard Schlenk-line
techniques. DMSO, phenol, o-apH2, o-bdH2, p-bdH2, o-anisidine, and
bis-2-aminophenyldisulfide were purchased from Wako Pure Chem-
ical Industries (Japan). Thiophenol, atpH2, m-apH2, p-apH2, DPD, 2-
amino-3-hydroxybenzoic acid (2A3H), 3-amino-2-hydroxybenzoic
acid (3A2H), 4-amino-3-hydroxybenzoic acid (4A3H), and 5-
amino-2-hydroxybenzoic acid (5A2H) were purchased from Tokyo
Chemical Industry Co., Ltd. (Japan). Dehydrated THF, acetonitrile-d3
(CD3CN), methanol-d4 (CD3OD), and m-bdH2 were purchased from
Kanto Chemical Co. Inc. (Japan). Chloroform-d (CDCl3) was
purchased from Sigma-Aldrich. 3-Amino-4-hydroxybenzoic acid
(3A4H) was purchased from Acros Organics (Belgium). THF was
where Nproducts refers to the amount of the products (mol), while Np
denominates the number of irradiated photons (Einstein).
Theoretical Calculations. Molecular orbitals and their energy for
each compound were obtained from DFT calculations at the CAM-
B3LYP/6-31G(d) level of using natural population analysis (NPA;61
solvent: THF). Solvent effects were taken into account via the
polarizable continuum model (IEFPCM).62 A set of quantum
chemical calculations at the time-dependent DFT (TDDFT)
calculations at the TD-CAM-B3LYP63/aug-cc-pVXZ (X = D, T)
level of theory were performed to determine the differences in the
photochemistry of o-, p-, and m-apH2. Using the Tamm−Dancoff
approximation, we performed geometry optimizations in order to
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Article
a
Table 2. Activation Energies for the ESHD in the
S1(π−π*) State of o-, m-, and p-ApH2 (in kcal mol−1)
theory
basis
o-apH2
m-apH2
p-apH2
b
CAM-B3LYP
aug-cc-pVDZ
aug-cc-pVTZ
aug-cc-pVDZ
9.1
8.5
7.2
16.6
15.6
13.8
8.9
7.7
7.9
CASPT2
a
Defined as the energy difference between the S1 minimum and the
b
S1(π−π*)/(π−σ*) structures. Tamm−Dancoff approximation was
applied.
Scheme 4. Resonance Structures of Phenoxy Radicals
Generated by ESHD Processes from (a) o-ApH2, (b) p-
ApH2, and (c) m-ApH2
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02456.
■
sı
Photophysical properties of all compounds; molecular
orbitals, energy diagrams, spin densities, and optimized
geometries obtained from DFT calculations; and UV−
1
vis, H NMR, and ESI-MS spectra under N2 and CO2
before and after photolysis (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Ho-Chol Chang − Department of Applied Chemistry, Faculty
of Science and Engineering, Chuo University, Tokyo 112-
8551, Japan; orcid.org/0000-0001-5159-2737;
Phone: +81-3-3817-1897; Email: chang@kc.chuo-u.ac.jp;
Fax: +81-3-3817-1895
Figure 5. (a) UV−vis spectra of THF solutions of p-apH2 (6.0 mM)
before irradiation under N2 (black) or CO2 (blue) and after
irradiation at λex = 300 10 nm for 8 h under N2 (green) or CO2
(red) at room temperature. 1H NMR (CD3OD, 400 MHz) spectra of
p-apH2 (b) before and after the photoirradiation for (c) 8 h, (d) 17 h,
and (e) commercial 5A2H at room temperature under a CO2
atmosphere. The symbols “#”, “*”, “‡”, and “+” indicate the signals
from residual protons of H2O, CD2HOD, THF, and DMSO. The full
1H NMR spectra are shown in Figure S17. (f,g) Negative ESI-MS
spectrum of the reaction solution of p-apH2 (f) before and (g) after
photoirradiation for 8 h under a CO2 atmosphere.
Authors
Kanae Abe − Department of Applied Chemistry, Faculty of
Science and Engineering, Chuo University, Tokyo 112-8551,
Japan
Akinobu Nakada − Department of Applied Chemistry, Faculty
of Science and Engineering, Chuo University, Tokyo 112-
8551, Japan; Precursory Research for Embryonic Science and
Technology (PRESTO), Japan Science and Technology
Agency (JST), Kawaguchi, Saitama 332-0012, Japan;
orcid.org/0000-0001-6670-5044
Takeshi Matsumoto − Department of Applied Chemistry,
Faculty of Science and Engineering, Chuo University, Tokyo
112-8551, Japan; Precursory Research for Embryonic Science
and Technology (PRESTO), Japan Science and Technology
Agency (JST), Kawaguchi, Saitama 332-0012, Japan
Daiki Uchijyo − Department of Applied Chemistry, Faculty of
Science and Engineering, Chuo University, Tokyo 112-8551,
Japan
search for conical intersection points for each molecule. To confirm
the accuracy of the TDDFT calculations, a set of single-point
calculations at the CASPT264/aug-cc-pVDZ level of theory was also
performed using the optimum structures obtained from the TDDFT
calculations. All calculations were carried out using the Gaussian16,65
GAMESS66 and open OpenMOLCAS67 quantum chemistry packages.
H
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(13) Yeung, C. S. Photoredox Catalysis as a Strategy for CO2
Incorporation: Direct Access to Carboxylic Acids from a Renewable
Feedstock. Angew. Chem., Int. Ed. 2019, 58, 5492−5502.
(14) Cao, Y.; He, X.; Wang, N.; Li, H.-R.; He, L.-N. Photochemical
and Electrochemical Carbon Dioxide Utilization with Organic
Compounds. Chin. J. Chem. 2018, 36, 644−659.
(15) Tan, F.; Yin, G. Homogeneous Light-Driven Catalytic Direct
Carboxylation with CO2. Chin. J. Chem. 2018, 36, 545−554.
(16) Gui, Y.-Y.; Zhou, W.-J.; Ye, J.-H.; Yu, D.-G. Photochemical
Carboxylation of Activated C(sp3)−H Bonds with CO2. ChemSu-
sChem 2017, 10, 1337−1340.
(17) He, X.; Qiu, L.-Q.; Wang, W.-J.; Chen, K.-H.; He, L.-N.
Photocarboxylation with CO2: an Appealing and Sustainable Strategy
for CO2 Fixation. Green Chem. 2020, 22, 7301−7320.
Hirotoshi Mori − Department of Applied Chemistry, Faculty
of Science and Engineering, Chuo University, Tokyo 112-
8551, Japan; Department of Theoretical and Computational
Molecular Science, Institute for Molecular Science, Okazaki
444-8585, Japan; orcid.org/0000-0002-7662-9636
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02456
Author Contributions
§K.A. and A.N. contributed equally.
Notes
The authors declare no competing financial interest.
(18) Zhang, Z.; Ye, J.-H.; Ju, T.; Liao, L.-L.; Haung, H.; Gui, Y.-Y.;
Zhou, W.-J.; Yu, D.-G. Visible-Light-Driven Catalytic Reductive
Carboxylation with CO2. ACS Catal. 2020, 10, 10871−10885.
(19) Jiang, Y.-X.; Chen, L.; Ran, C.-K.; Song, L.; Zhang, W.; Liao, L.-
L.; Yu, D.-G. Visible-Light Photoredox-Catalyzed Ring-Opening
Carboxylation of Cyclic Oxime Esters with CO2. ChemSusChem
2020, 13, in press. DOI: 10.1002/cssc.202002032
(20) Murata, K.; Numasawa, N.; Shimomaki, K.; Takaya, J.;
Iwasawa, N. Construction of a Visible Light-Driven Hydrocarbox-
ylation Cycle of Alkenes by the Combined Use of Rh(I) and
Photoredox Catalysts. Chem. Commun. 2017, 53, 3098−3101.
(21) Hou, J.; Ee, A.; Feng, W.; Xu, J.-H.; Zhao, Y.; Wu, J. Visible-
Light-Driven Alkyne Hydro-/Carbocarboxylation Using CO2 via
Iridium/Cobalt Dual Catalysis for Divergent Heterocycle Synthesis.
J. Am. Chem. Soc. 2018, 140, 5257−5263.
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ACKNOWLEDGMENTS
■
The authors are grateful to Prof. Masa-aki Haga (Chuo
University) for his support with the measurement of emission
spectra. All the presented quantum chemical calculations were
carried out at the Research Center for Computational Science
(RCCS) in the Okazaki Research Facilities at the National
Institutes of Natural Sciences (NINS). This work was funded
by JSPS KAKENHI grants JP16H04123, JP16K13967,
JP17H04871, and JP19K23652, as well as by MEXT
KAKENHI grants JP17H05382 (Coordination Asymmetry),
JP18H05517 (Hydrogenomics), and JP20H05113 (I4LEC), by
PRESTO grant JPMJPR16SA (JST), and by the Research
Promotion Fund from the Promotion and Mutual Aid
Corporation for Private Schools of Japan.
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