Photocatalysis by phenothiazine dyes: Visible-light-driven oxidative coupling of primary amines at ambient temperature

Article abstract of DOI:10.1021/ol302584y

New phenothiazine based organic dyes were prepared for visible-light-driven organic transformations. The 3,7-disubstituted phenothiazine derivatives showed visible light absorption and reversible one-electron oxidation behavior. In the presence of 0.5 mol

Full text of DOI:10.1021/ol302584y

ORGANIC
LETTERS
2012
Vol. 14, No. 21
5502–5505
Photocatalysis by Phenothiazine Dyes:
Visible-Light-Driven Oxidative Coupling of
Primary Amines at Ambient Temperature
Ji Hoon Park,† Kyoung Chul Ko,† Eunchul Kim,‡ Nojin Park,‡ Ju Hong Ko,†
Do Hyun Ryu,† Tae Kyu Ahn,*,‡ Jin Yong Lee,*,† and Seung Uk Son*,†,‡
Department of Chemistry and Department of Energy Science,
Sungkyunkwan University, Suwon 440-746, Korea
sson@skku.edu
Received September 20, 2012
ABSTRACT
New phenothiazine based organic dyes were prepared for visible-light-driven organic transformations. The 3,7-disubstituted phenothiazine
derivatives showed visible light absorption and reversible one-electron oxidation behavior. In the presence of 0.5 mol % of 3,7-disubstituted
phenothiazines, primary benzylamines showed oxidative coupling under visible light irradiation from a blue LED. The electronic effect of
substituents in phenothiazine dyes was observed in catalytic activities. The mechanistic pathway of oxidative coupling was discussed based on
the detection of H2O2 after the reaction.
As energy issues become more and more important in
modern life, many scientific studies have sought the devel-
opment of new sustainable energy resources.1 Among
them, solar energy is one of the most attractive resources.2
It is well-known that solar light contains 43% visible light.2
Thus, chemical transformations triggered by visible light
are energetically beneficial.3
Recently, photoredox catalysis using visible light har-
vesting dyes has shown successful results in a variety of
chemical transformations.4 Usually, ruthenium or iridium
complexes have been used as dyes in these reactions. In
addition to efforts for expansion of the range of organic
reactions, further studies are definitely required for more
diverse dyes including organic dyes.
Imines are versatile building blocks in various organic
transformations such as nucleophilic addition and cyclo-
addition.5 Besides the conventional preparation methods
such as condensation of carbonyl and amines, imines can
be prepared from secondary amines by visible-light-driven
aerobic oxidation.6 Furthermore, imines can be prepared
by intriguing oxidative coupling of primary amines.7 It is
noteworthy that studies on the oxidative coupling of
primary amines to imines were relatively less explored than
simple oxidation of secondary amines. The oxidative
coupling of primary amines can be catalyzed by transition
(5) March, J. Advanced Organic Chemistry, 4th ed.; John Wiley and
Sons: Chichester, U.K., 1992.
(6) (a) Jiang, G.; Chen, J.; Huang, J.-S.; Che, C.-M. Org. Lett. 2009,
11, 4568. (b) Zhu, B.; Angelici, R. J. Chem. Commun. 2007, 2157. (c) So,
M.-H.; Liu, Y.; Ho, C.-H.; Che, C.-M. Chem.;Asian J. 2009, 4, 1551.
(d) Aschwanden, L.; Panella, B.; Rossbach, P.; Keller, B.; Baiker, A.
ChemCatChem 2009, 1, 111.
(7) (a) Patil, R. D.; Adimurthy, S. Adv. Synth. Catal. 2011, 353, 1695.
(b) Huang, H.; Huang, J.; Liu, Y.-M.; He, H.-Y.; Cao, Y.; Fan, K.-N.
Green Chem. 2012, 14, 930. (c) Liu, L.; Zhang, S.; Fu, X.; Yan, C.-H.
Chem. Commun. 2011, 47, 10148. (d) Kodama, S.; Yoshida, J.; Nomoto,
A.; Ueta, Y.; Yano, S.; Ueshima, M.; Ogawa, A. Tetrahedron Lett. 2010,
51, 2450.
† Department of Chemistry.
‡ Department of Energy Science.
(1) Hileman, B. Chem. Eng. News 2006, 84, 70.
(2) Nozik, A. J.; Miller, J. Chem. Rev. 2010, 110, 6443.
(3) (a) Ciamician, G. Science 1912, 36, 385. (b) Albini, A.; Fagnoni,
M. Green Chem. 2004, 6, 1.
(4) Recent reviews: (a) Tucker, J. W.; Stephenson, C. R. J. J. Org.
Chem. 2012, 77, 1617. (b) Narayanam, J. M. R.; Stephenson, C. R. J.
Chem. Soc. Rev. 2011, 40, 1259.
r
10.1021/ol302584y
Published on Web 10/12/2012
2012 American Chemical Society

metal complexes, and others, without visible light.7aꢀc
However, the reaction temperatures were around 100 °C.
Very recently, several reports appeared on the photo-
catalytic conversion of primary amines to imines.8 For
example, Zhao and co-workers reported a TiO2-based
photocatalytic system for aerobic oxidative coupling
of primary amines with a 100 W Hg lamp (wavelength
>300 nm).8a Nitta’s group reported a metal-free photo-
catalytic system with an ∼84 turnover number (TON)
using a 350 nm lamp.8b,c Wang and Blechert group re-
ported metal-free carbon nitride photocatalysts with visi-
ble light (wavelength >420 nm) at 80 °C.8d Although
catalytic systems operated by visible light have appeared
in recent literatures,8d more exploration is definitely re-
quired for more efficient photocatalytic systems which can
conduct reactions with higher TONs at ambient temperature.
In this work, we report highly efficient phenothiazine dyes
for the photocatalytic oxidative coupling of primary amine
at ambient temperature. As far as we are aware, this is the
most active visible-light-driven photocatalytic system for
the oxidative coupling of primary amines.
by Vilsmeier reaction of N-butylphenothiazine.5 Arylcyano
groups were then introduced by nucleophilic condensa-
tion with aldehyde groups.5 The prepared dyes (D1ꢀD6)
were fully characterized by 1H NMR, 13C NMR, and high
resolution mass spectroscopy (refer to the Supporting
Information (SI)).
Scheme 2. Synthesis of Phenothiazine Dyes (D1ꢀD6)
In the literature, there have been several mechanistic
suggestions on the photocatalytic oxidative coupling of
primary amines to imines.7,8 For example, the photoin-
duced generation of aldehyde and successive imination
were suggested for coupled imine formation. In addition,
alternative intermediates such as benzenemethanimine
were suggested. In these catalytic photoredox mechanisms,
electron transfer to oxygen by the photoexcited dyes and
abstraction of electrons from amines were generally de-
scribed (Scheme 1). Nontheless, the photoinduced singlet
oxygen pathway by dyes without electron transfer to
oxygen cannot be excluded.6a,9
The optical and electrochemical properties of the pre-
pared dyes (D1ꢀD6) were studied by UVꢀvis absorption
spectroscopy and cyclic voltammetry (Figure 1 and Table 1).
The dyes showed maximum absorption peaks in the
402ꢀ447 nm range. As more electron-donating groups
were attached at the 4-position of the side phenyl groups,
the locations of the maximum absorption peak were
gradually blue-shifted. At the same time, reversible one-
electron oxidation potentials were gradually shifted to
less positive values, indicating a more facile oxidation
Scheme 1. Photoredox Catalysis between Oxygen and Amines
Induced by Light Harvesting Dyes
Scheme 2 shows synthetic routes for phenothiazine dyes
used in this study. N-Butylphenothiazine with 3-carbox-
aldehyde or 3,7-dicarboxaldehyde groups were prepared
(8) (a) Lang, X.; Ji, H.; Chen, C.; Ma, W.; Zhao, J. Angew. Chem., Int.
Ed. 2011, 50, 3934. (b) Mitsumoto, Y.; Nitta, M. J. Org. Chem. 2004, 69,
1256. (c) Naya, S.-I.; Yamaguchi, Y.; Nitta Tetrahedron 2005, 61, 7384.
(d) Su, F.; Mathew, S. C.; Mohlmann, L.; Antonietti, M.; Wang, X.;
Blechert, S. Angew. Chem., Int. Ed. 2011, 50, 657.
(9) See the Figure S1 in the SI for more detailed discussion.
Figure 1. UVꢀvis absorption spectra of dyes (D1ꢀD6) (a) and
representative cyclic voltammogram with five scans (b) of D6.
€
Org. Lett., Vol. 14, No. 21, 2012
5503

(Figure S2 in the SI). Using onset UVꢀvis absorption
peaks and oxidation potentials of the dyes, the locations of
the HOMO and LUMO were calculated (Table 1). As the
electronic surrounding of the dyes became more electron-
rich, the HOMO and LUMO were moved to higher energy
levels.
observed. In the absence of D6, the catalytic system
showed no conversion (entry8). These observationsclearly
support that oxidative couplings proceeded by a photo-
catalytic process. In optimized conditions, the catalytic
system with 0.50 mol % D6 showed 100% conversion at
room temperature after 20 h (entry 9).
Table 1. Optical and Electrochemical Properties of
Phenothiazine Dyes (D1ꢀD6)a
Table 2. Photocatalytic Oxidative Coupling of Benzylamine
Induced by Phenothiazine Dyes (D1ꢀD6)a
ox. potentialb E0ꢀ0 HOMOd LUMOe
c
λmax, ε
dyes (nm, Mꢀ1 cmꢀ1
)
(V)
(eV)
(eV)
(eV)
Dl
416, 14800
406, 16000
402, 16400
447, 20000
434, 20400
433, 21200
0.48 (rev)f
0.47 (rev)
0.45 (rev)
0.53 (rev)
0.51 (rev)
0.48 (rev)
2.54
2.59
2.62
2.36
2.41
2.43
ꢀ5.23
ꢀ5.23
ꢀ5.22
ꢀ5.26
ꢀ5.25
ꢀ5.22
ꢀ2.69
ꢀ2.64
ꢀ2.60
ꢀ2.88
ꢀ2.83
ꢀ2.78
D2
D3
D4
D5
D6
amount of
dye (mol %)b
yield
(%)c
entry
dye
1
2
3
4
5
6
7d
8
9
Dl
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0
22
24
46
51
80
83
0
D2
D3
D4
D5
D6
D6
ꢀ
a Acetonitrile was used as solvent. b Potentials vs Ag/Agþ (reference
electrode) determined in a conventional three electrode cell by using
0.10 M tetrabutylammonium hexafluorophosphate (TBAPF6) in acet-
onitrile as the supporting electrolyte, indium tin oxide (ITO) glass as the
working electrode, and platinum as the counter electrode. c 0ꢀ0 transi-
tion energies measured using the onset of UVꢀvis absorption spectra.
d HOMO values calculated using potentials of oxidative waves. e LUMO
values obtained from HOMO þ E0ꢀ0. f Reversible peaks.
0
D6
0.50
100
a Reaction conditions: 1 mmol of benzylamine, 1 atm of oxygen,
3 mL of acetonitrile, blue LED, rt, and 20 h. b Mol % to benzylamine.
c Conversion yield based on 1H NMR spectroscopy. d The glassware was
completely coated with Al foil before LED irradiation.
Considering the visible light absorption behavior and
reversible one-electron oxidation properties, we applied the
dyes D1ꢀD6 to the photocatalytic oxidative coupling
of primary amines. The benzylamine was irradiated with
blue LED in the presence of 0.25 mol % dyes and 1 atm
of oxygen. Acetonitrile (80% conversion with D5, entry 5
in Table 2) was selected as the best solvent after DMSO
(69%) and toluene (4%) were also considered. The tem-
perature of the reaction mixture was maintained below 30 °C
using a circulated water bath. As shown in entries 1ꢀ6 in
Table 2, the dyes (D4ꢀD6) with two side groups at the 3,7-
positions showed better activities than those (D1ꢀD3) with
one side group. Among D4ꢀD6, the more electron-rich dyes
showed better reactivities. The 0.25 mol % D6 showed 83%
conversion of benzylamine to the coupled imine. As far as
we are aware, this is one of the most active photocatalytic
systems for oxidative coupling of primary amines.8
As shown in Scheme 1, cationic radical dye species would
be formed in photocatalytic processes by electron transfer
to oxygen. The instability of this cationic radical species
results in low TONs of the catalytic cycle. The highly
catalytic performances of the dyes in this work might
originate from the unique stability of the cationic radical
of phenothiazines. As shown in Figure 1b, the oxidized
species of D6 underwent reversible redox conversion. It is
noteworthy that the unique reversible redox process of
phenothiazines has been applied to display devices.10
In a control experiment (entry 7), when glassware
covered with aluminum foil was used, no conversion was
To rationalize the photoredox process, the energy levels
of the used materials were considered. As expected, the
LUMO of oxygen was lower than that of D6. However,
the HOMO of benzylamine was lower than that of D6
(Figures S3ꢀS5 in the SI). Interestingly, the SOMO of
oxidized D6 was lower than the HOMO of benzylamine,
indicating that the photoredox process in this work follows
the oxidative quenching pathway.4 The more electron-rich
dye showed a higher LUMO, facilitating the electron
transfer from dyes to oxygen (Table 1). Moreover, the
higher fluoresence quantum yield was observed in more
electron-rich dyes (Figure S6 in the SI). Thus, it can be
speculated that the increase of catalytic activities from D4
to D6 resulted from the more efficient electron transfer of
excited states to oxygen.
The photocatalytic system using D6 was applied to
various amines (Table 3). The electronic effect of substitu-
ents on arenes of benzyl amines was insignificant in con-
version (entries 1ꢀ4). 2-Thiophenmethylamine showed
88% conversion (entry 5). The methyl group in the
R-carbon of benzylamine dramatically retarded the con-
version (entry 6). The photocatalytic system showed good
activity in the simple oxidation of the secondary amine
(entry 7). However, alkylamines were not converted to
the coupled imines. Instead, octylamine could be used as
a coupling partner of benzylamine (entry 8).
€
(10) (a) Gratzel, M. Nature 2001, 409, 575. (b) Cummins, D.; Boschloo,
Several mechanisms of oxidative coupling of primary
amines in the literature7,8 are summarized in Figure 2a.
G.; Ryan, M.; Corr, D.; Rao, S. N.; Fitzmaurice, D. J. Phys. Chem. B 2000,
104, 11449.
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Org. Lett., Vol. 14, No. 21, 2012

Table 3. Photocatalytic Oxidative Coupling of Amines by D6a
a Reaction conditions: 1 mmol of amine, 1 atm of oxygen, 0.5 mol %
D6, 3 mL of acetonitrile, blue LED, rt, and 20 h. b Conversion yield
based on 1H NMR spectroscopy. The values in parentheses indicate
isolated yields. c Additional 3 mmol of octylamine was used.
In path A, the formation of benzaldehyde and successive
condensation resulted in the coupled imine. In path B, the
formation of benzenemethanimine and successive addi-
tion of amine resulted in the coupled imine and H2O2.
In paths C and D, the generated H2O2 acts as an additional
oxidant. In paths A, C, and D, the H2O2 will not be
detected. Interestingly, after reaction using D6, a quanti-
Figure 2. (a) Suggested reaction pathways of oxidative coupling of
primary amines to imines through photocatalysis. (b) The detec-
tion of H2O2 by 1H NMR spectroscopy after reaction using D6.
1
tative amount of H2O2 was detected at 10.2 ppm in H
Acknowledgment. This work was supported by Grants
NRF-2011-0029186 (Midcareer Researcher Program) and
NRF-2012-1040282 (Priority Research Centers Program).
N.P. is thankful for grant R31-2008-10029 (WCU
program).
NMR spectrosocpy (Figure 2b). Considering the integra-
tion of peaks, the amount of H2O2 was very close to a 1:1
ratio to the product, which strongly indicates that the
oxidativecoupling in this workfollows path B inFigure 2a.
In conclusion, new photocatalytic systems were devel-
oped using 3,7-disubstituted phenothiazine dyes which
showed reversible one-electron oxidation behaviors. The
photocatalytic systems with 0.5 mol % dye D6 showed
complete conversion of benzylamine at room temperature.
The reaction mechanism was suggested by detection
of H2O2 as a byproduct. We believe that the prepared
phenothiazine dyes can be further applied to more diverse
photochemical transformations.
Supporting Information Available. Experimental pro-
cedure for preparation of new compounds and their
characterization data, additional optical and electroche-
mical characterization data, DFT calculations. This ma-
terial is available free of charge via the Internet at http://
pubs.acs.org.
The authors declare no competing financial interest.
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