Organic Letters
Letter
of the initially formed singlet photoexcited state of EY (τS = 6
2 ns) to its triplet photoexcited state (EY*) (τT = 320 10
ns).21 Further, reductive quenching of the EY* by an aromatic
amine generates an amine radical cation via a one-electron
oxidation.19a,22 EY•− is a powerful reducing agent (EY•− to EY
is −1.06 V), and it has a lifetime of 500 10 ns; it is quenched
by molecular oxygen to accomplish the photoredox cycle.18
Then a strongly basic superoxide anion (O2•−), deprotonated a
relatively acidic amine radical cation and an aminyl radical was
generated.14,19b Next, the hydroperoxyl radical abstracts an H
atom in a single step or in a series of steps (H+ + e−) from the
ortho substituents (XH) of the aminyl radical.21 The
generation of the o-quinone-diimine intermediate (I1 in Figure
3) was proved by high-resolution mass spectroscopy (HR-MS)
for OPDA (Figure SI7a). Further, the adduct formed with
(2,2,6,6-tetramethylpiperidine-1-yl)oxyl (TEMPO) and I1 was
trapped in HR-MS, which supports the generation of I1 (Figure
SI9a). Despite this, a rate inhibition was observed for TEMPO,
which also suggests that the reaction is going through a radical
pathway (Figure SI8, UV−vis study). Earlier, Sousa et al.
proposed I1 as an intermediate for phenazine synthesis from
OPDA in the presence of laccases.5 The same intermediate was
also trapped by Jiang et al. using an online electrochemistry−
mass spectrometry technique.23 The formation of the transient
superoxide radical was also confirmed through HR-MS using
5,5-dimethyl-1-pyrroline N-oxide (DMPO), a selective scav-
enger for superoxide (Figure SI9b).24 A kinetic study revealed
the enhancement of the reaction rate under an O2 atmosphere
(100%) in comparison to air (21%) for OPDA (Figure SI10),
which supports the involvement of O2 in the reaction.
amines in water in very good yields (≥80%) at RT. For a 1
mmol scale, an ∼80% yield was observed for OPDA. The
reaction proceeds through the generation of highly reactive
electrophilic species such as o-quinone-diimine or o-quinone-
imine. Then an amino group of another substrate molecule
acts as a nucleophile and attacks the most electrophilic carbon
atom (in the position para to the quinonic group) of the
reactive intermediate in a classic 1,4-conjugated Michael
addition and generates the first coupling intermediate, which
undergoes intramolecular cyclization toward product forma-
tion. This method can be considered a valuable alternative to
known methods for the rational synthesis of phenazine- and
phenoxazinone-based heterocycles.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
Experimental section, kinetics data, HPLC, HR-MS,
NMR, and optimized geometries (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Basab Bijayi Dhar − Department of Chemistry, School of
Natural Sciences, Shiv Nadar University, Dadri, Uttar
In the same way, the formation of an o-quinone-imine
intermediate was proposed for o-aminophenol precursors.5
The highly reactive o-quinone-diimine or ortho-quinone-imine
was involved in a 1,4-conjugated Michael addition, on its most
electrophilic carbon atom (in the para position to the quinonic
group), with an amino group of another substrate molecule.5
Further, a proton shift yielded the first coupling intermediate
(I2 in Figure 3), and then the 2e− oxidation of I2 would have
been possible by the H2O2 generated during the reaction.
H2O2 was detected by adding a potassium iodide solution
(Figure SI11), but no effect on the reaction rate or percentage
yield was observed in the presence of the catalase. This
indicates that the H2O2 produced in the reaction did not
participate in further oxidation; therefore, the second 2e−
oxidation was expected to be mediated by another photoredox
cycle of EY. The reaction went through the formation of a 4-N-
aryl o-quinone-diimine species (I3), and it was captured by
revealed that, in the second photoredox cycle of EY, the
reductive quenching of EY* by I2 is even more favorable than
that in the first photoredox cycle by the substituted aromatic
amines. Then, a proton shiftfollowed by an intramolecular
Michael addition of the amino group (or phenol) to the C5
atomleads to the formation of the aminophenazine or fully
reduced aminophenoxazine.
Authors
Ashish Kumar Dhara − Department of Chemistry, School of
Natural Sciences, Shiv Nadar University, Dadri, Uttar
Pradesh 201314, India
Sayantan Maity − Department of Chemistry, School of
Natural Sciences, Shiv Nadar University, Dadri, Uttar
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
A.K.D. acknowledges the CSIR of India (grant number:
80(0086)/17/EMR-II) for a research fellowship. S.M.
acknowledges Shiv Nadar University (SNU) for a research
fellowship. B.B.D. acknowledges the SNU and CSIR of India
(Grant No. 80(0086)/17/EMR-II) for funding. The authors
acknowledge MAGUS, the High Performance Computing
Cluster of SNU, and Mr. Dwaipayan Chakraborty, Department
of Physics, SNU, for helpful discussions regarding theoretical
analysis. The authors are thankful to Mr. Surit Das for editing
the manuscript.
The reduced aminophenoxazine is spontaneously oxidized
by aerial oxygen to produce the desired heterocycle. The
reaction was not inhibited by the addition of a singlet oxygen
quencher such as 1,4- diazabicyclo[2.2.2]octane (DABCO),
which suggests that singlet oxygen is not necessary.
In conclusion, we developed an efficient, inexpensive, metal-
free photocatalytic method of synthesizing phenazine and
phenoxazinone derivatives from ortho-substituted aromatic
REFERENCES
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