Synthesis of 2-substituted benzothiazoles by visible light-driven photoredox catalysis

Article abstract of DOI:10.1002/adsc.201300376

An efficient method for synthesis of the widely applicable 2-substituted benzothiazoles has been developed. The process requires only 0.1 mol% [Ru(bpy)₃Cl₂], O₂, and visible light irradiation with substrates: 2-aminothiophenol and a variety of aldehydes. We established an oxidative quenching of the photoredox catalyst as being the key process in this photoelectrocatalytic cycle. Copyright

Full text of DOI:10.1002/adsc.201300376

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DOI: 10.1002/adsc.201300376
Synthesis of 2-Substituted Benzothiazoles by Visible Light-Driven
Photoredox Catalysis
Chunghyeon Yu,a Kyungyub Lee,a Youngmin You,b,* and Eun Jin Choa,*
a
Department of Chemistry and Applied Chemistry, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan,
Kyeonggi-do 426-791, Republic of Korea
Fax : (+82)-31-400-5457; e-mail: echo@hanyang.ac.kr
Department of Advanced Materials Engineering for Information and Electronics, Kyung Hee University, Yongin-si,
b
Kyeonggi-do 446-701, Republic of Korea
E-mail: odds2@khu.ac.kr
Received: May 1, 2013; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300376.
Abstract: An efficient method for synthesis of the
widely applicable 2-substituted benzothiazoles has
been developed. The process requires only
0.1 mol% [RuACHTUNGTRENNUNG(bpy)3Cl2], O2, and visible light irradi-
ation with substrates: 2-aminothiophenol and a vari-
ety of aldehydes. We established an oxidative
quenching of the photoredox catalyst as being the
key process in this photoelectrocatalytic cycle.
À
Keywords: benzothiazoles; benzothiazolines; C H
oxidation; radical reaction; visible light
The benzothiazole structural motif has been of great
importance in many applications (Figure 1).[1,2] It is
widely used in pharmaceuticals with a diverse range
of biological properties, and currently the use of ben-
zothiazole in the preparation of organic optoelectron-
ic materials is gaining in importance[3].
Figure 1. Molecules containing the benzothiazole structural
motif.
through an imine 3 or a benzothiazoline 4 as key in-
Consequently, great effort has been made to devel- termediate (Scheme 1). It is assumed that the inter-
op efficient processes for the preparation of benzo- mediates 3 and 4 are in equilibrium and their conver-
thiazole derivatives.[4,5] Since many of currently avail- sion to 5 proceeds by either or both of the following
able synthetic methods rely on hazardous materials two possible pathways; radical thiol-ene type reaction
requiring costly containment and disposal (e.g., con- of imine 3 (pathway A)[8] or a-amino C H oxidation
À
centrated acids and high loadings of metal catalysts), of benzothiazoline 4 (pathway B)[9].
the development of more efficient and convenient
We began by examining the benzothiazole synthesis
methods is still desired. Herein we present an alterna- from aminothiophenol 1 and octanal 2a under visible
tive, environmentally benign method for benzothia- light-induced photoredox catalysis. To our delight, the
zole synthesis from 2-aminothiophenol and aldehydes desired benzothiazole product 5a was obtained in
with molecular oxygen as oxidant by visible light- a 80% yield using 0.5 mol% of [RuACHTUNRTGNEUNG(bpy)3Cl2] (bpy=
driven photoredox catalysis.[6,7] Mechanistic studies 2,2’-bipyridine) as the photoredox catalyst in an air-
were further performed to establish the key action of equilibrated MeCN solution under photoirradiation
the photoredox catalyst.
by blue LEDs (Scheme 2).
We envisioned that a 2-substituted benzothiazole 5
We investigated the reaction mechanism to confirm
could be obtained via photoredox radical reactions that the reaction proceeds by photoredox catalysis
between 2-aminothiophenol 1 and an aldehyde 2 and to determine the reaction pathway. For this pur-
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Table 1. Radical a-amino C H oxidation of benzothiazoline
4a.[a]
Scheme 1. Hypothesis for the visible light-induced synthesis
of benzothiazoles.
[a]
Scheme 2. Benzothiazole synthesis by the photoredox cataly-
sis.
Reaction conditions: 4a (0.2 mmol), photoredox catalyst
(0.5 mol%), MeCN (2 mL), room temperature, 3 h.
phen=1,10-phenanthroline,
ppy=2-phenylpyridinate,
dtb-bpy=4,4’-di-tert-butyl-2,2’-bipyridine.
The yield was determined by GC-MS with dodecane as
an internal standard.
[b]
pose we originally planned to isolate possible inter-
mediates and run reactions using them to produce 5a.
Although we expected to isolate the imine 3a, which
has been predicted as the intermediate in most previ- [Ru
ous studies, in a mixture with benzothiazoline 4a, we charge separation.
(bpy)3]2+ predominated, barely contributes to the
ACHTUNGTRENNUNG
could only isolate benzothiazoline 4a without even
Photon absorption by the MLCT transition in
1
detecting 3a by H NMR spectroscopy.[10] Thus, we [Ru(II)
G
pursued the mechanistic studies using the isolated 4a separated species, [Ru
G
G
CHTUNGTRENNUNG
only.[11] Both blue LEDs as the visible light source ed-state oxidation (E*ox) and reduction (E*red) poten-
and oxygen were essential for the reaction to proceed tials of [RuACHTUGNTREN(NUGN III)ACHTUGTNENRN(UG bpy)2ACUTHNGTRENNUNG
(Table 1, entries 2 and 3). Although a range of Ru 1.08 V, respectively (vs. SCE), as determined by cyclic
and Ir photoredox catalysts were found to give the voltammetry and steady-state optical measurements
desired benzothiazole 5a in good yields, [RuACTHNUTRGNEUNG(bpy)3Cl2] (see the Supporting Information, Figures S1 and S2).
was chosen for further studies because of its low cost. Judging from these potential values and the oxidation
(Table 1, entries 1 and 5–7). The reaction showed potential of 4a (0.61 V, vs. SCE), two photoredox
À
better efficiency with blue LEDs than with a fluores- routes to the radical a-amino C H oxidation of 4a
cent light bulb (Table 1, entries 1 and 4).
can be suggested. The first route is the direct oxida-
To verify the catalytic activity of [RuACTHNGUTRNEN(GU bpy)3Cl2], tion of 4a:
conversion yields (Y1h) were measured by GC-MS for
the air-equilibrated MeCN solutions containing 4a
and 0.5 mol% [Ru
ACHTUGNTERN(NUNG bpy)3Cl2], after 1 h photoirradia-
tion at varying wavelengths (lex =300–450 nm). As
The driving force for the electron transfer (ÀDGeT)
(bpy)CÀ]2+ is 0.47 eV, as esti-
shown in Figure 2 (a), a significant improvement in from 4a to [RuACHTUNGTREN(NNGU III)ACHTUNTRGEG(NNNU bpy)2ACHTNUGTRENNUGN
Y1h was observed at wavelength >380 nm which cor- mated by ÀDGeT =e·
responded to the metal-to-ligand charge-transfer The other route is the two-step process that involves
(MLCT) transition band of [Ru (III)(bpy)2A
(bpy)3]2+.[12] The coin- the reduction of O2 by [Ru (bpy)CÀ]2+ to
(III)
(bpy)3]3+, fol-
(III)
(bpy)3]3+:
[E8ox(4a)ÀE*red(Rucomplex)].
G
A
R
CHTUNGTRENNUNG
cidence between the photoaction profile (i.e, Y1h) and form superoxide (O2CÀ) and [Ru
A
ACHTUNGTRENNUNG
the MLCT absorption band strongly suggests the key lowed by the oxidation of 4a by [Ru
A
ACHTUNGTRENNUNG
role of the photoinduced intramolecular charge sepa-
ration in [RuACHTUNGTRENNUNG
(bpy)3]2+. On the contrary, Y1h remained
below 20% at lex <380 nm. This result can be ex-
plained by the fact that the region (i.e., lex <380 nm),
where the absorption by 4a and the bpy ligand of
2
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Synthesis of 2-Substituted Benzothiazoles by Visible Light-Driven Photoredox Catalysis
Figure 2. (a) UV-Vis absorption spectra of 4a and [Ru
yields obtained after 1 h photoirradiation at different photoirradiation wavelengths in the region of 300–450 nm. (b) Photolu-
minescence decay traces of 50 mM [Ru(bpy)3Cl2] in argon-saturated MeCN (filled circles), O2-equilibrated MeCN (empty cir-
ACHTUNGTREN(NUNG bpy)3Cl2] (10 mM in deaerated MeCN). Filled circles are conversion
AHCTUNGTRENNUNG
cles), and argon-saturated MeCN containing 50 mM 4a (triangles) after nanosecond photoexcitation at 377 nm.
In this case, the overall driving force is the fer rate of kobs =4.77ꢁ106 sÀ1. In sharp contrast, the
sum
e·
[E8ox(4a)ÀE8redox(Ru
Thus, the first and second routes characterized by the sence of the direct photoinduced electron transfer be-
reductive and the oxidative quenching, respectively, tween 4a and [Ru
(bpy)3]2+ (the reductive quenching).
are thermodynamically favourable. In fact, dominance of the oxidative quenching (i.e.,
of
e·
N
and addition of 50 mM 4a had no apparent influence on
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
To detect a preference between the two photoredox O2 reduction followed by electron transfer from 4a)
routes suggested above, we monitored the transient over the reductive quenching is anticipated due to the
photoluminescence (lobs =620 nm) of [Ru
the presence of either O2 or 4a. As shown in Figure 2
(b), the photoluminescence lifetime (tobs
[Ru
1.02 ms to 0.174 ms, corresponding to an electron trans- [Ru(II)
ACHTUNGTREN(UNGN bpy)3Cl2] in larger driving force (i.e., 0.91 eV vs. 0.47 eV).
Based on these results, we propose a plausible
À
)
of mechanism for the a-amino C H oxidation
(bpy)3Cl2] was significantly shortened by O2 from (Figure 3).
The
MLCT
photoexcitation
of
(bpy)3]2+ by visible light promotes the intra-
Figure 3. Proposed mechanism of the benzothiazole synthesis.
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Chunghyeon Yu et al.
Table 3. Syntheses of 2-substituted benzothiazoles.[a]
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Table 2. Optimization study for the synthesis of benzothia-
zoles.
[a]
The yield was determined by GC-MS with dodecane as
an internal standard.
molecular
[Ru(III)(bpy)
cies is oxidatively quenched by O2 to produce
charge
separation
to
generate
A
R
CHTUNGTRENNUNG
[Ru
[Ru
N
G
and
superoxide.
The
returning to [Ru(II)ACHTUNGTRENNUNG
by superoxide followed by hydrogen atom abstraction
by hydroperoxyl radical (HOOC) yields the desired
benzothiazole 5a. The H2O2 generated in the last step
1
was detected by H NMR spectroscopy (d=8.8 ppm
in CD3CN)[14] and an H2O2 indicator,[15] which strong-
ly supports our hypothesis.
Having understood the visible light-driven photore-
dox catalytic mechanism, we further explored optimal
conditions for benzothiazole synthesis with 2-amino-
thiophenol 1 and octanal 2a in the presence of [Ru-
[a]
[b]
Reaction conditions:
[Ru(bpy)3Cl2] (1.0 mmol), MeCN (5.0 mL), blue LEDs,
room temperature, 3–10 h.
Isolated yields based on an average of two runs. Num-
bers in parentheses indicate yield obtained under the
1
(1.1 mmol),
2
(1.0 mmol),
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG(bpy)3Cl2] (Table 2). Although the reaction proceeded
well in a variety of solvents including DMF, CH2Cl2,
and methanol, it worked best in MeCN at a 0.2M
concentration (Table 3, entries 1–7). The presence of
molecular sieves did not influence the reactivity sig-
nificantly (Table 3, entry 8). The result also suggested
that the presence of water formed from the condensa-
standard reaction conditions where [Ru
cluded.
ACHTUNGTRENN(NUG bpy)3Cl2] was ex-
With the optimized conditions in hand, we evaluat-
tion between 1 and 2a does not affect the reactivity. ed the reactions of 2-aminothiophenol with a variety
The catalyst loading can be lowered down to of aldehydes for the synthesis of 2-substituted benzo-
0.1 mol% without loss in yield (Table 3, entries 9–11). thiazoles (Table 3). Both aliphatic and aromatic alde-
A slight excess of 1 gave a higher yield of 5a and hydes are suitable substrates and provide benzothia-
made it easier to purify the product.
zoles in good to excellent yields. In addition, reactions
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Synthesis of 2-Substituted Benzothiazoles by Visible Light-Driven Photoredox Catalysis
Scheme 3. Reactions of substituted 2-aminothiophenols.
of both electron-poor and electron-rich aromatic alde- Experimental Section
hydes gave high yields of products. The mild reaction
conditions allowed for benzothiazole syntheses in the General Procedure
presence of a range of functional groups such as aryl
An open test tube equipped with a magnetic stir bar was
halides (5g, 5h) and heteroaromatic (5k) systems. The
current reaction conditions were amenable to a large-
scale reaction such that 5d was prepared on a 5
nmmol scale with the yield being similar to that of
a 1 mmol scale reaction. Notably, reactions proceeded
even in the absence of the photocatalyst, as expected
from the large positive driving force for the photoin-
duced electron transfer from the benzothiazoline
charged with 2-aminothiophenol (1.1 mmol). Then were
added MeCN (5.0 mL, 0.20M), an aldehyde (1.0 mmol), and
[RuACTHNURTGNE(NUG bpy)3Cl2] (0.10 mol%, 1.0 mmol). The open test tube
was placed under blue LEDs and the mixture allowed to stir
at room temperature for 3–10 h. Reaction progress was
checked by thin layer chromatography (TLC)[17] or gas chro-
matography (GC). The reaction mixture was concentrated
under vacuum, and benzothiazole products were purified by
flash column chromatography.
inter
e·
N
N
vs. SCE). However, due to the very small absorbance
in the visible region, the reaction took much longer
(>15 h)[16] and resulted in much lower yields, which
Acknowledgements
indicates the crucial role of [RuACHTUNTGRNEUNG(bpy)3Cl2].
Reactions of substituted 2-aminothiophenols such
as 2-amino-4-chlorobenzenethiol 6 and 2-amino-4-(tri-
This work was supported by the National Research Founda-
tion of Korea (NRF) under Grants No. NRF-2011-0013118
and NRF-2012M3A7B4049657 (Nano Material Technology
Development Program).
fluoromethyl)benzenethiol
8 also gave excellent
yields of the desired benzothiazole products
(Scheme 3).
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To summarize, we have developed a protocol for
the synthesis of 2-substituted benzothiazoles using
visible light-induced photoredox catalysis. This proto-
col is noteworthy for the mild reaction conditions, en-
abling the preparation of a broad range of benzothia-
zoles, and for minimizing toxic waste by using
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[15] A peroxide indicator, QUANTOFIX Peroxid 25, was
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[16] Most of the reactions did not go to completion even
upon longer times in the absence of a photocatalyst
and gave lower yields of the products as shown in
Table 3.
[17] We observed several unidentified compounds by TLC.
Although these were easily seen by UV or a stain (p-
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than 1% based on the weight.
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Synthesis of 2-Substituted Benzothiazoles by Visible Light-
Driven Photoredox Catalysis
7
Adv. Synth. Catal. 2013, 355, 1 – 7
Chunghyeon Yu, Kyungyub Lee, Youngmin You,*
Eun Jin Cho*
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