The Hofmann reaction involving annulation of: O -(pyridin-2-yl)aryl amides selectively and rapidly leads to potential photocatalytically active 6 H -pyrido[1,2- c] quinazolin-6-one derivatives

Article abstract of DOI:10.1039/d0gc02777d

A highly efficient PIFA-mediated Hofmann reaction of o-(pyridin-2-yl)aryl amides has been developed to selectively and rapidly construct various potential photocatalytically active 6H-pyrido[1,2-c]quinazolin-6-one derivatives. The use of a nontoxic and ec

Full text of DOI:10.1039/d0gc02777d

View Article Online
View Journal
Green
Chemistry
Cutting-edge research for a greener sustainable future
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: W. Gao, Y. Wan, Z.
Zhang, H. Wu, T. Liu and G. Zhang, Green Chem., 2020, DOI: 10.1039/D0GC02777D.
Volume 20
This is an Accepted Manuscript, which has been through the
Number
May 2018
Pages 1919-2160
9
7
Royal Society of Chemistry peer review process and has been
accepted for publication.
Green
Chemistry
Cutting-edge research for a greener sustainable future
rsc.li/greenchem
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 1463-9262
PAPER
Paul T. Anastas et al.
The Green ChemisTREE: 20 years after taking root with the 12
principles
rsc.li/greenchem

Please do not adjust margins
Page 1 of 7
Green Chemistry
View Article Online
DOI: 10.1039/D0GC02777D
Journal Name
ARTICLE
Hofmann reaction-involving annulation of o-(pyridin-2-yl)aryl
amides selectively and rapidly leads to potential potocatalytic
active 6H-pyrido[1,2-c]quinazolin-6-one derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
Wenjing Gao,†a Yameng Wan,†a Zhiguo Zhang,*a Hao Wu,a Tongxin Liua and Guisheng Zhang*a
DOI: 10.1039/x0xx00000x
A highly efficient PIFA-mediated Hofmann reaction of o-(pyridin-2-yl)aryl amides has been developed to selectively and
rapidly construct various potential potocatalytic active 6H-pyrido[1,2-c]quinazolin-6-ones. The use of nontoxic and eco-
friendly organoiodine reagent, operationally simplicity, short reaction time and mild reaction conditions, broad substrate
scope and high functional group tolerance, and excellent yields make this protocol very simple, practical, and easy to handle.
It provides a feasible platform for developing novel organic fluorophore structures. Preliminary research for this purpose
shows that the N5-methylated pyridoquinazolinone 3a could be used as a photocatalyst in several organic transformations,
indicating it is a very promising lead fluorophore for developing new superior photocatalysts.
www.rsc.org/
Molina in 1992 from o-(2-pyridinyl)aniline via sequential diazo-
reaction, azidation, Staudinger reaction, and subsequent
pyrido annelation with CO2 (Scheme 1a).5 Since then, the sole
Introduction
Organic fluorophores are of great interest in diverse scientific
fields like photocatalytic chemistry, materials science, and
chemical biology due to their high sensitivity, structural
versatility, high chemical stability, good specificity, and
synthetic accessibility.1 Photocatalysis, which utilizes light as a
clean energy source, has attracted considerable attention
from green and synthetic chemists and gained prominence in
orchestrating challenging organic transformations under mild
reaction conditions.1f-k The conjugated organic dyes as
cyanoarenes, xanthenes, and acridiniums have been utilized
for metal-free photocatalysis,2 which has demonstrated a high
photocatalytic efficiency for both oxidation3 and reduction
reactions.4 However, certain disadvantages of organic
photocatalysts including low redox capacity, photobleaching,
and limited light-responsive nature restrict their broad range
of applications. Therefore, the discovery of new photocatalytic
active organic fluorophores is still highly desirable for
development of new class of organic photocatalysts.
alternative method was proposed through an one-step
reaction of toxic phosgene with o-(2-pyridinyl)aniline in the
presence of polymersupported diisopropylamine (PS-DIA)
(Scheme 2b).6 Besides the environmentally unfriendly and
health risks associated with use of phosgene, there are also
major problems associated with its production and storage. To
date, there are not convenient and practical approaches to
diverse pyridoquinazolinone derivatives.
Previous works:
O
NH2
N3
N
1 NaNO2, HCl
2 NaN3
a
1 PPh3
2 CO2
N
N
N
2a
O
H
N
O
N
NH2
N
phosgene
PS-DIPA
- H+
N
b
N
NMe2
NMe2
NMe2
This work:
O
N
O
O
C
N
N
6H-Pyrido[1,2-c]quinazolin-6-one (2a, Scheme 1) containing
dentate N atom and rigid structure with N-embedded
extended conjugated π-systems is a promising privileged
skeleton for organic semiconductors and potential catalyst
backbone. Pyridoquinazolinone 2a was firstly synthesized by
PIFA
R1
NH2
N
R1
c
N
R1
MeCN, r.t.
R2
R2
R2
2
1
NH2
N
R2
R2
R1
N
N
R1
H
H
R2
N
N
R1
O
Scheme 1. Synthetic routes to pyrido[1,2-c]quinazolin-6-ones.
a. Key Laboratory of Green Chemical Media and Reactions, Ministry of Education,
Collaborative Innovation Center of Henan Province for Green Manufacturing of
Fine Chemicals, Henan Key Laboratory of Organic Functional Molecule and Drug
Innovation, School of Chemistry and Chemical Engineering, Henan Normal
University, Xinxiang, Henan 453007, China. E-mail: zhangzg@htu.edu.cn or
zgs@htu.cn
The discovery of new photocatlyst candidates belonging to
this class is seriously restricted to the lack of readily available
structurally diverse pyridoquinazolinoniun derivatives. So far,
the structural improvements of pyridoquinazolinoniun and
applications in photocatalysis have not been reported.
†These authors contributed equally to the publication
Electronic Supplementary Information (ESI) available: [1H, 13C NMR spectrum,
HRMS, fluorescence emission spectra and single crystal X-ray diffraction data]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 2 of 7
ARTICLE
Journal Name
-
Practical and efficient methods of general synthetic
applicability are therefore highly desirable. We report herein
an efficient and straightforward method to rapid construct the
diverse 6H-pyrido[1,2-c]quinazolin-6-one structures via a
novel intramolecular Hofmann rearrangement reaction of
readily available primary o-(pyridin-2-yl)aryl carboxamide
Nu
C
View Article Online
DOI: 10.1039/D0GC02777D
O
IIII
O
R
a
or
R
NH2
R
N
O
N
Nu
R
NH2
H
-
Nu = Amines, Alcohols, Water etc.
O
ArNH2
O
O
IIII
C
C
O
Ar
Ar
N
N
mediated by
a
hypervalent organoiodine reagent bis-
N
H
b
N
2
Ar
NH2
H
Ar
Ar
(trifluoroacetoxy) iodobenzene (PIFA) in mild conditions
(Scheme 1c). These reactions were simply conducted by
stirring a solution of amides and PIFA in CH3CN at room
temperature within 1 h to selectively produce a wide variety
of 6H-Pyrido[1,2-c]quinazolin-6-one derivatives in excellent
yields. The simple procedure, high chemoselectivity and
excellent yields, short reaction time, mild reaction condition,
and the use of nontoxic and environmentally benign
hypervalent organoiodine reagent make this protocol very
simple, practical, and easy to handle.
Without additonal nucleophilic reagent
Scheme 2. IIII-promoted Hofmann reactions of amides.
TfO
O
I
Ph
I
Ph
PIFA
O
N
O
TfO
C
N
NH2
R1
N
N
OTf
R1
R1
H
R2
-PhI, -TfOH
-TfOH
R2
R2
N
1
B
A
N
O
Results and discussion
N
O
R1
R1
N
N
Hypervalent organoiodine reagents (IIII) have been widely used
in organic transformations, serving as advanced oxidants
features of their nontoxicity, ready availability,
environmentally benign and ease of handling characteristics.7
And the IIII-promoted Hofmann rearrangements of amides for
the construction of various N-containing functional organic
molecules has been benefits for green synthetic chemistry,
chemicobiology, and pharmaceutical chemistry etc.8 In general,
these processes afforded primary amines via Hofmann
degradation by releasing carbonyl moiety, or generated urea
and carbamate derivatives via a process of N-, O-nucleophilic
attack to the C atom in the isocyanate group, which is an
incomplete rearrangement intermediate forming from
corresponding primary amides (Scheme 2a). To date, amines,
alcohols, even water had been used as the nucleophiles in the
Hofmann rearrangement involved cascade transformation via
an inter- or intramolecular process. In the absence of
additional nucleophilic reagent, however, the primary amides
always generated symmetric urea derivatives with the amino
group, which is generated in situ, serving as the nucleophile
(Scheme 2b).9 Accordingly, we envisioned that readily
available primary o-(pyridin-2-yl)aryl carboxamide 1 mediated
by a hypervalent organoiodine reagent (e.g. PIFA) might be
give an iodoimidate intermediate A via an intermolecular
nucleophilic attack of 1 to PIFA, then A rearrangement yielded
isocyanate B by losing a molecule PhI and TfOH. Next, ring
closure of B via an intramolecular nucleophilic attack of the
pyridyl N atom to the C atom of isocyanate group and the
electron reorganization might give pyridoquinazolinones 2
(Scheme 3). The aromaticity of the extended conjugated π-
systems 2 might provide a means for driving the selective
formation of 2 instead of the formation of corresponding
amines and ureas.
R2
R2
2
Scheme 3. Proposed mechanism.
In recent years, we concerning on the hypervalent
organoiodine compounds promoted the construction of the N-
containing fused-heterocycles.10 These ring closure
procedures proceeded generally in high yield and allowed to
access various N-containing five-, six-membered fused or
spiro-heterocycles. Based on our experiences with
hypervalent iodine reagents-promoted oxidative coupling
reactions, we began our evaluation with o-(pyridin-2-
yl)benzamide (1a) as a model substrate (Table 1), which was
readily prepared by Suzuki reaction and nitrile hydrolysis,11
and a series of hypervalent organoiodine reagents were first
investigated. To our delight, the desired product 2a was
formed in 91% yield in the presence of 1.1 equiv of PIFA at
room temperature after 30 min in MeCN solvent (entry 1). The
experiment showed that upon reducing the PIFA loading from
1.1 equiv to 0.5 equiv, the yield of 2a dropped from 91% to
66%, and 1a was recovered in 30% (entry 2). It was found that
the yield of 2a was not significantly improved when we
increased the PIFA loading from 1.1 equiv to 1.5 equiv (entry
3).
Other
organoiodine
reagents
including
diacetoxyiodobenzene (III) (PIDA), iodosylbenzene (III) (PhIO),
and 2-iodoxybenzoic acid (V) (IBX) were screened and they
were found to be not as efficient as PIFA, especially for IBX
which was ineffective to the transformation and 91% of
substrate 1a was recovered (entries 4-6). When the solvent
was switched to THF, MeOH, DMSO, and DMF, product 2a was
obtained in lower yields (31-83%) than that in MeCN (entry 1
vs. 7-10). After screening, the optimal reaction conditions
eventually emerged as 1a (0.2 mmol) and PIFA (1.1 equiv) in
MeCN (2 mL) at room temperature.
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 7
Green Chemistry
Please do not adjust margins
Journal Name
ARTICLE
Table 1 Optimization of the reaction conditionsa
products (2s-u) in excellent yields, which were obviously
higher than that of the product bearing an electron-
withdrawing bromo group (2v). To our delight, the expected
product 5H-pyrido[1,2,3-cd]perimidin-5-one (2x) was
obtained in 92% yield after 15 min when benzo[h]quinoline-
10-carboxamide (1x) was used as the starting material.
View Article Online
DOI: 10.1039/D0GC02777D
O
C
N
O
NH2
C
N
Conditions
N
2a
1a
Table 2 Reaction extensiona
Entry
Catalyst
(equiv)
Solvent Yieldsb of
1a
2a /%
(Recovery)
O
1
2
3
4
5
6
7
8
9
PIFA (1.1)
PIFA (0.5)
PIFA (1.5)
PIDA (1.1)
PhIO (1.1)
IBX (1.1)
PIFA (1.1)
PIFA (1.1)
PIFA (1.1)
PIFA (1.1)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
91
66
92
53
56
0
30
0
30
35
91
0
9
0
55
C
N
O
NH2
R2
C
N
R1
R1
PIFA
R2
MeCN, r.t.
N
2
1
O
O
O
O
trace
83
N
C
N
C
N
C
N
C
N
N
N
N
MeO
MeOH
DMSO
DMF
64
70
31
2a
2b
2c
2d
30 min, 91%
20 min, 98%
20 min, 96%
20 min, 90%
O
O
O
O
10
N
C
N
C
N
C
N
C
N
N
N
N
aReaction conditions: 1a (0.2 mmol), PIFA (1,1 equiv), in
MeCN (2 mL) at room temperature for 30 min. Isolated
yield of the pure product 2a.
F
b
F
2g
2e
2f
2h
30 min, 98%
30 min, 97%
15 min, 97%
20 min, 96%
O
O
O
O
N
C
N
C
N
C
N
C
With the optimized conditions in hand (Table 1, entry 1), we
investigated the substrate scope of this PIFA-promoted
Hofmann rearrangement-involved tandem reaction (Table 2).
Firstly, various R1 substituents were investigated, and the
results indicated that a number of functional groups including
–Me, –OMe, –tBu, –CF3, –F, –CN, –Ph, –N(Ph)2, –N(Me)2, and
9H-carbazol-9-yl at the 3-, 4-, 5-, and/or 6-positions were
tolerated well to the reaction, regardless of the electronic
effect. The target products 2b–n were isolated in excellent to
almost quantitative yields (90−99%). It is worth mentioning
that there is a nitrile group in compound 2j, which is useful for
further derivatization. Compounds 2l and 2n bearing a N,N-
diphenyl group and 9H-carbazol-9-yl, respectively, should be
especially popular with people who are engaged in
optoelectronic materials. To our delight, -pyridyl--
naphthamide 1o also underwent well to produce polycyclic
compound 2o in 98% yields. Similarly, the reaction of aza- or
thia-heteroaryl amides 1p and 1r gave corresponding products
2p and 2r in yields of 87% and 90%, respectively. However,
compound 1q failed to the desired product 2q under the
optimized conditions, and a complex mixture was observed.
Compared with the starting materials 1p and 1q, the nitrogen
atom at the ortho-position of primary amide group inhibited
the Hofmann rearrangement process of 1q obviously.
Unfortunately, we don't know why such a small change on the
substrate structure has so big impact on the reaction at
present. Then, a limited diversity of R2 substituents was tested
due to the inherent limitations of substrate synthesis.
Preliminary investigation indicated that the methyl
substituted pyridyl (2s and 2t), Methoxyl pyridyl (2u),
bromopyridyl (2v), and quinoline group (2w) can be tolerated
to the transformation. The substrates bearing an electron-
donating group in pyridyl moiety (1s-u) gave corresponding
N
N
N
N
F3C
Ph
Ph2N
CN
2j
2i
2k
2l
20 min, 92%
20 min, 95%
10 min, 99%
30 min, 95%
O
C
N
O
C
N
O
C
N
O
N
C
N
N
N
N
N
N
Me2N
2p
2m
2n
2o
60 min, 98%
30 min, 90%
60 min, 98%
60 min, 87%
O
C
N
O
O
O
N
N
C
N
C
N
C
N
N
N
N
S
2q
2s
2t
2r
2 h, 0%b
20 min, 91%
30 min, 93%
30 min, 90%
O
O
O
C
N
O
N
C
N
C
N
N
C
N
N
N
OMe
Br
2u
2w
2x
2v
30 min, 93%
45 min, 89%
15 min, 92%
25 min, 78%
aReaction conditions: 1a (0.2 mmol) and PIFA (1,1 equiv) in
MeCN (2 mL) at room temperature under air atmosphere,
isolated yield of the pure product 2. bComplex mixture.
Furthermore, to demonstrate the productive practicability
of this reaction,
benzo[h]quinoline-10-carboxamide 2x also got a satisfied
result (Scheme 4).
a
gram-scale preparation of
O
O
N
N
NH2
N
PIFA (1.1 equiv), r.t.
CH3CN (15 mL), 20 min
1x
2x
: 0.93 g, 85%
: 1.11 g
Scheme 4. Gram-scale preparation of 2x
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 4 of 7
ARTICLE
Journal Name
The excitation and emission spectra for fluorescence
compounds 2 were detrmined (Figure S2). As the basic
to conduct the cross couplings with substituted arenes. Under
View Article Online
the conditions given in table 4, 3a can effectively catalyze the
DOI: 10.1039/D0GC02777D
oxidative C(sp2)-H amination of arenes bearing electron-
donating groups gave good yields (4a-4e) but ineffective to
electron-deficient arenes (e.g.4f).
backbone structure of
pyridoquinazolinones 2, 2a was
selected to investigate the potential applications in
photocatalytic chemistry. Its fluorescence emission spectra
were measured in MeCN at room temperature and shown in
table 3. Upon excitation at 416 nm, linear N-embedded
triacene 2a emitted fluorescence in the green to yellow region
Table 4 Photocatalytic site-selective oxidative C–H/N–H cross-
coupling between arenes and azolesa
(λem = 507 nm), and has an excited state lifetime
τ (7.2 ns).
Inspired by Fukuzumi’s pioneering work of 9-mesityl-10-
methylacridinium perchlorate12 that has been utilized
effectively in a variety of transformations,3f,13 we initially
considered introducing a methyl group at N5 position of 2a into
a methylated pyridoquinazolinonium salt 3a for improving its
photocatalytic properties (Table 3). As depicted in table 3, 75%
yield of 3a was obtained when 2a was reacted with (Me3O)BF4
in a mixed solvent of acetonitrile and dichloromethane (DCM).
The structure of 3a was unequivocally determined by single-
crystal X-ray diffraction (Figure S1). Gratifyingly, 3a has a
longer excited state lifetime τ (9.4 ns), a positive excited state
reduction potential (E*1/2 = +2.32 V vs SCE), and a negative
ground state reduction potential (E1/2(C/C−) = −0.65 V vs SCE)
(Table 3), and show its comparability to the well-known 9-
mesityl-10-methylacridinium perchlorate.
N
N
X
3a (1 mol%), O2, DCE
h  350 nm, r.t.
X
+
R
HN
R
N
X = N, C
4
N
N
N
N
MeO
N
MeO
N
PhO
N
4a
: 24 h, 60%; 6:1 p:o
4c
: 1 h, 71%
4b
: 5 h, 55%
N
N
N
N
N
N
PhO
N
Ph
N
Cl
N
4d
4e: 30 h, 59%
: 4 h, 64%
4f
: NR
aReaction conditions: arenes (0.2 mmol), azoles (0.4 mmol)
and 3a (0.002 mmol) in dichloroethane (DCE, 2 mL) under O2
atmosphere, irradiation by 350 nm cobalt lamps, isolated
yield of the pure product 4.
Table 3 The preparation of 3a from 2aa and their Photophysical
Properties
Traditionally, amides are prepared from the condensation of
acylating agents with amines, which needs either coupling
agents or conversion into more reactive derivatives. The direct
oxidative addition of amines to aromatic aldehydes under mild
and metal-free conditions provided a more economic and eco-
friendly method for accessing amides.15 Inspired by the good
results of applying in oxidative cross-coupling between arenes
and azoles, 3a was applied for the oxidative cross-couplings
between aromatic aldehydes and secondary amines (Table 5).
To our delight, the aromatic aldehydes bearing electron-
donating or withdrawing groups all underwent the direct
amidation smoothly to give the desired amides in high yields
(5a–5f, 80%–90%).
BF4
O
N
O
N
(Me3O)BF4, rt, 24 h
N
N
MeCN:DCM (3:1)
75% yield
2a
3a
E1/2(C*/C-)b
E1/2(C/C-)c
τ
λex
λem
(V)
(V)
(ns)
(nm)
(nm)
2a
3a
/
/
7.2
9.4
416
382
507
474
2.32
-0.65
Table 5 Photocatalytic oxidative C–H/N–H cross-coupling
between aryl aldehydes and aminesa
aReaction conditions: 2a (0.2 mmol) and (Me3O)BF4 (3.0
equiv) in MeCN/CH2Cl2 (2 mL) at room temperature. bExcited
state reduction potentials were estimated from ground state
redox potentials and the intersection of the absorption and
emission bands. cDetermined by cyclic voltammetry in
acetonitrile versus saturated calomel electrode (SCE).
O
O
3a
(2 mol%), O2,1,4-Dioxane
HN
+
Ar
N
h  350 nm, r.t.
Ar
H
5
O
O
O
N
O
N
N
With these promising results in hand, we next investigated
the photocatalytic reactivity of 3a in several metal-free organic
transformations.
NC
NC
NC
5b
5c
: 40 h, 89%
: 20 h, 88%
5a
: 48 h, 90%
O
O
O
Direct cross-coupling between arenes and heterocyclic
amines under mild and metal-free conditions is undoubtedly
important for C–N bonds formation. Selective C(sp2)-H
amination under mild and metal-free conditions is more
valuable and challenge.14 Recently, Nicewicz reported an
acridinium photocatalyst-promoted site-selective amination
of aromatics with heteroaromatic azoles, without the need for
prefunctionalization of the aromatic component.14 In our
initial investigations for photocatalysis activity of 3a, we
selected pyrazole and triazole as representative nucleophiles
N
N
N
N
S
MeO
5f
5d
: 20 h, 88%
5e
: 24 h, 81%
: 20 h, 80%
aReaction conditions: aryl aldehyde (0.2 mmol), amine (0.8
mmol) and 3a (0.004 mmol) in dioxane (2 mL) under O2
atmosphere, irradiation by 350 nm cobalt lamps, isolated
yield of the pure product 5.
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 7
Green Chemistry
Please do not adjust margins
Journal Name
ARTICLE
aReaction conditions: thioether (0.2 mmol) and 3a (0.002
mmol) in MeCN (2 mL) under air atmosphere, irradiation by
350 nm cobalt lamps, isolated yield of the pure product 7.
The selective oxidation of benzylamine and its derivatives to
imines, which are regarded as useful and active electrophilic
intermediates for organic transformations, is an important
laboratory and commercial procedure, and is often used as a
model organic reaction for testing photocatalyst activity.3h,16
The above results encouraged us to investigate the application
of 3a in the photocatalytic aerobic oxidative self-coupling of
benzylamines under irradiation by 350 nm cobalt lamps. Under
the conditions given in table 6, 3a is effective to the selective
oxidations to give the desired imines in moderate to good
yields (6a–6f, 37%–78%).
View Article Online
DOI: 10.1039/D0GC02777D
Experimental
General information. 1H NMR and 13C NMR spectra were
recorded on a 400/600 MHz NMR spectrometer (1H NMR,
400/600 MHz; 13C NMR, 100/150 MHz at 25 °C). Coupling
constants are reported in Hz. All high-resolution mass spectra
(HRMS) were measured on a mass spectrometer (ESI-oa-TOF).
All reagents were purchased from commercial sources and
used without further treatment. All reactions were monitored
by thin layer chromatography (TLC).
Table
6
Photocatalytic oxidative self-couplings of
benzylaminesa
3a
(2 mol%), O2, MeCN
Ar
NH2
Ar
N
Ar
General procedure for synthesis of compound 2 (2a as an
example). To a round-bottom flask (25 mL) was added 1a (39.6
mg, 0.2 mmol), PIFA (94.6 mg, 0.22 mmol), the reaction was
allowed to stir for 30 min in CH3CN (2 mL) at room temperature
until completion. The reaction mixture was treated with
saturated NaHCO3 solution (5 mL), and extracted with DCM
(3×10 mL). The combined organic layer was dried over
anhydrous MgSO4, and concentrated on a rotary evaporator.
The crude product was further purified by recrystallized with
ethyl ether to produce the desired 2a as a yellow solid (35.6
mg, 91%).
Preparation procedure of compound 3a. To a round-bottom flask
(25 mL) was added 2a (59.0 mg, 0.3 mmol), (Me3O)BF4 (133.0
mg, 0.9 mmol), the reaction was allowed to stir for 24 h in a
mixed solvent of CH3CN and DCM (3 : 1, 3 mL) at room
temperature until completion. The reaction was quenched
with water (10 mL), and extracted with DCM (3×15 mL). The
combined organic layers were dried over anhydrous MgSO4,
and concentrated on a rotary evaporator. The crude product
was further purified by recrystallized with ethyl ether to
produce the desired 3a as a yellow solid (67.0 mg, 75%).
General procedure for synthesis of compound 4-7 (4d as an
example). In a sealed quartz tube with a magnetic stir bar were
placed anisole (21.6 mg, 0.2 mmol), 1H-1,2,3-triazole (27.6 mg,
0.4 mmol), 3a (0.6 mg, 0.002 mmol), and DCE (2 mL) under O2
atmosphere. The reaction was stirred for 10 h under the
irradiation by 350 nm cobalt lamps at room temperature. TLC
was used to monitor the progress of the reaction. After the
reaction was complete, the reaction mixture was concentrated
and the crude product was further purified by column
chromatography (petroleum ether/ethyl acetate) to give the
desired 4d (24.8 mg, 71%).
h  350 nm, r.t.
6
N
N
N
MeO
OMe
CF3
6c
: 30 h, 78%
6a
: 20 h, 74%
6b
: 26 h, 66%
N
N
N
S
S
Cl
Cl
F3C
6f
: 24 h, 37%
6d
: 24 h, 36%
6e
: 24 h, 40%
aReaction conditions: benzylamines (0.2 mmol) and 3a
(0.004 mmol) in MeCN (2 mL) under O2 atmosphere,
irradiation by 350 nm cobalt lamps, isolated yield of the pure
product 6.
Photocatalytic selective oxidation of thioethers into
sulfoxides without using additives was the most
straightforward, environmentally friendly, atom-economical
approach to sulfoxides.3h,17 To further investigate its
photocatalytic activity, 3a was subjected to the sulfides
transformation. Under the conditions given in table 6, 3a could
effectively catalyze the sulfide transformation with excellent
selectivity without obtaining the unwished sulfone caused by
overoxidation. Various thioether substrates bearing methyl,
ethyl, cyclopropyl, and methoxy functionalities could be
selectively oxidized with high yields (7a–7e, 80%–86%), except
for the substrate bearing a strong electron-withdrawing cyano
group which was converted to sulfoxide 7f with a moderate
yield.
Table 7 Photocatalytic selective oxidation of sulfidesa
O
3a
(1 mol%), air, MeCN
S
S
Ar
R
h  350 nm, r.t.
Ar
R
7
Conclusions
O
S
O
O
S
O
S
O
O
S
S
In summary, we have developed an efficient and
straightforward method to rapid construct the diverse 6H-
Pyrido[1,2-c]quinazolin-6-ones in excellent yields under mild
reaction conditions via a novel intramolecular Hofmann
rearrangement reaction of readily available primary o-
(pyridin-2-yl)aryl carboxamide mediated by PIFA. The simple
S
MeO
7d
: 15 h, 84%
NC
7e
: 9 h, 86%
7a
: 12 h, 84%
7b
: 11 h, 80%
7c
: 20 h, 86%
7f
: 9 h, 40%
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 6 of 7
ARTICLE
Journal Name
Huang, C. Ayed, L. Wang, K. A. I. Zhang, ACS Catal. 2018, 8,
procedure, high chemoselectivity and excellent yields, short
reaction time, mild reaction condition, the use of nontoxic and
environmentally benign hypervalent organoiodine reagent,
and broad substrate scope and high functional group tolerance
make this protocol very simple, practical, and easy to handle.
Furthermore, the N5-methylated derivative 3a exhibits a good
photocatalytic activity in the photocatalyses of site-selective
oxidative C–H/N–H cross-coupling between arenes and azoles,
oxidative C–H/N–H cross-coupling between aryl aldehydes and
amines, oxidative self-couplings of benzylamines, and
selective oxidation of sulfides. Further modifications on the
promising pyrido[1,2-c]quinazolin-6-one structure to find
novel photocatalysts with a superior activity are ongoing in our
laboratory.
View Article Online
4735.
DOI: 10.1039/D0GC02777D
4
(a) I. Ghosh, T. Ghosh, J. I. Bardagi, B. König, Science 2014,
346, 725. (b) D. P. Hari, P. Schroll, B. König, J. Am. Chem. Soc.
2012, 134, 2958. (c) G. Pandey, S. Hajra, M. K. Ghorai, K. R.
Kumar, J. Am. Chem. Soc. 1997, 119, 8777. (d) S. Gazi, R.
Ananthakrishnan, Appl. Catal., B 2011, 105, 317. (e) I. Ghosh,
L. Marzo, A. Das, R. Shaikh, B. König, Acc. Chem. Res. 2016,
49, 1566.
5
6
7
P. Molina, A. Lorenzo, E. Aller, Tetrahedron 1992, 48, 4601.
M. D. Markey, T. R. Kelly, Tetrahedron 2008, 64, 8381
(a) R. Zhao, Lei Shi, Angew. Chem. Int. Ed. 2020, 59, 12282.
(b) A. Yoshimura, V. V. Zhdankin, Chem. Rev. 2016, 116, 3328.
(c) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008, 108, 5299.
(d) A. Maity, B. L. Frey, N. D. Hoskinson, D. C. Powers, J. Am.
Chem. Soc. 2020, 142, 4990. (e) T. H. El-Assaad, K. N. Parida,
M. F. Cesario, D. V. McGrath, Green Chem. 2020, DOI:
10.1039/d0gc02000a. (f) Y. Wan, Z. Zhang, N. Ma, J. Bi, G.
Zhang, J. Org. Chem. 2019, 84, 780. (g) Z. Zhang, X. Li, M.
Song, Y. Wan, D. Zheng, G. Zhang, G. Chen, J. Org. Chem.
2019, 84, 12792. (h) Y.-N. Ma, C.-Y. Guo, Q. Zhao, J. Zhang, X.
Chen, Green Chem., 2018, 20, 2953. (i) Z. Zhang, D. Zheng, Y.
Wan, G. Zhang, J. Bi, Q. Liu, T. Liu, L. Shi, J. Org. Chem. 2018,
83, 1369. (j) S. Kumar, N. Ahmed, Green Chem., 2016, 18, 648.
(a) E. Aresu, S. Fioravanti, S. Gasbarri, L. Pellacani, F.
Ramadori, Amino acids 2013, 44, 977. (b) K. Miyamoto, Y.
Sakai, S. Goda, M. Ochiai, Chem. Commun. 2012, 48, 982.(c)
A. L. J. Beckwith, L. K. Dyall, Aust. J. Chem. 1990, 43, 451. (d)
S. Verbeeck, W. A. Herrebout, A. V. Gulevskaya, B. J. Veken,
B. U. W. Maes, J. Org. Chem. 2010, 75, 5126.
Conflicts of interest
There are no conflicts to declare.
8
9
Acknowledgements
We thank the NSFC (U1604285 and 21877206), PCSIRT
(IRT1061), the 111 Project (D17007).
(a) P. Liu, Z. M. Wang, X. M. Hu, Eur. J. Org. Chem. 2012,
1994. (b) C. H. Senanayake, L. E. Fredenburgh, R. A. Reamer,
R. D. Larsen, T. R. Verhoeven, P. J. Reider, J. Am. Chem. Soc.
1994, 116, 7947. (c) K. Tanabe, A. Taniguchi, T. Matsumoto,
K. Oisaki, Y. Sohma, M. Kanai, Chem. Sci. 2014, 5, 2747. (d)
G. Angelici, S. Contaldi, S. L. Green, C. Tomasini, Org. Biomol.
Chem. 2008, 6, 1849.
Notes and references
1
For reviews, see: (a) J. Zhang, R. E. Campbell, A. Y. Ting, R. Y.
Tsien, Nat. Rev. Mol. Cell Biol. 2002, 3, 906. (b) M. S. T.
Gonçalves, Chem. Rev. 2009, 109, 190. (c) H. Kobayashi, M.
Ogawa, R. Alford, P. L. Choyke, Y. Urano, Chem. Rev. 2010,
110, 2620. (d) Y. Tao, K. Yuan, T. Chen, P. Xu, H. Li, R. Cheng,
C. Zheng, L. Zhang, W. Huang, Adv. Mater. 2014, 26, 7931.
(e) X. Li, X. Gao, W. Shi, H. Ma, Chem. Rev. 2014, 114, 590. (f)
J. M. R. Narayanam, C. R. J. Stephenson, Chem. Soc. Rev.,
2011, 40, 102. (g) L. Shi, W. Xia, Chem. Soc. Rev., 2012, 41,
7687. (h) J. Xuan, W.-J. Xiao, Angew. Chem. Int. Ed., 2012, 51,
6828. (i) C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem.
Rev., 2013, 113, 5322. (j) J. Zhao, W. Wu, J. Sun, S. Guo,
Chem. Soc. Rev., 2013, 42, 5323. (k) X. Lang, X. Chen, J. Zhao,
Chem. Soc. Rev., 2014, 43, 473.
(a) M.-M. Wang, J. Waser, Angew. Chem. Int. Ed. 2020, 59, 1.
(b) N. Holmberg-Douglas, N. P. R. Onuska, D. A. Nicewicz,
Angew. Chem. Int. Ed. 2020, 59, 7425. (c) P. Wang, S. Zhu, D.
Lu, Y. Gong, Org. Lett. 2020, 22, 1924. (d) T. Alam, A. Rakshit,
P. Begum, A. Dahiya, B. K. Patel, Org. Lett. 2020, 22, 3728. (e)
J. Schwarz, B. König, Green Chem., 2016, 18, 4743. (f) N. A.
Romero, D. A. Nicewicz, Chem. Rev. 2016, 116, 10075. (g) D.
A. Nicewicz, T. M. Nguyen, ACS Catal. 2014, 4, 355. (h) D. P.
Hari, B. Konig, Chem. Commun. 2014, 50, 6688. (i) W.-J. Yoo.
S. Kobayashi, Green Chem., 2013, 15, 1844. (j) Y. Pan, S.
Wang, C. W. Kee, E. Dubuisson, Y. Yang, K. P. Loh, C.-H. Tan,
Green Chem., 2011, 13, 3341.
10 (a) H. Wu, Z. Zhang, Q. Liu, T. Liu, N. Ma, G. Zhang, Org. Lett.
2018, 20, 2897. (b) Z. Zhang, S. Wang, C. Hu, N. Ma, G. Zhang,
Q. Liu, Tetrahedron 2018, 74, 7472. (c) Z. Zhang, D. Zheng, N.
n. Ma, J. Bi, Chin. J. Org. Chem. 2017, 37, 1824. (d) Z. Zhang,
Y. Zhang, G. Huang, G. Zhang, Org. Chem. Front. 2017, 4,
1372. (e) Z. Zhang, X. Gao, Z. Li, G. Zhang, N. Ma, Q. Liu, T.
Liu, Org. Chem. Front. 2017, 4, 404. (f) Z. Zhang, F. Zhang, H.
Wang, H. Wu, X. Duan, Q. Liu, T. Liu, G. Zhang, Adv. Synth.
Catal. 2015, 357, 2681. (g) Z. Zhang, S. Fang, Q. Liu, G. Zhang,
Adv. Synth. Catal. 2012, 354, 927.
11 (a) C. Liu, N. Han, X. Song, J. Qiu, Eur. J. Org. Chem. 2010,
5548. (b) C. Qi, X. Hu, H. Jiang, Chem. Commun. 2017, 53,
7994. (c) M. Chaitanya, D. Yadagiri, P. Anbarasan, Org. Lett.
2013, 15, 4960.
12 S. Fukuzumi, H. Kotani, K. Ohkubo, S. Ogo, N. V. Tkachenko,
H. Lemmetyinen, J. Am. Chem. Soc. 2004, 126, 1600.
13 (a) A. J. Perkowski, D. A. Nicewicz, J. Am. Chem. Soc. 2013,
135, 10334. (b) T. M. Nguyen, D. A. Nicewicz, J. Am. Chem.
Soc. 2013, 135, 9588. (c) T. M. Nguyen, N. Manohar, D. A.
Nicewicz, Angew. Chem. Int. Ed. 2014, 53, 6198.
14 N. A. Romero, K. A. Margrey, N. E. Tay, D. A. Nicewicz, Science
2015, 349, 1326
15 (a) R. Tank, U. Pathak, M. Vimal, S. Bhattacharyya, L. K.
Pandey, Green Chem. 2011, 13, 3350. (b) X.-F. Wang, S.-S. Yu,
C Wang, D. Xue, J. Xiao, Org. Biomol. Chem. 2016, 14, 7028.
(c) D. Leow, Org. Lett. 2014, 16, 5812.
16 (a) Q. Xiao, T. U. Connell, J. J. Cadusch, A. Roberts, A. S. R.
Chesman, D. l E. Gomez, ACS Catal. 2018, 8, 10331. (b) C. Xu,
H. Liu, D. Li, J.-H. Sub, H.-L. Jiang, Chem. Sci., 2018, 9, 3152.
(c) H. Li, Y. Yang, C. He, L. Zeng, C. Duan, ACS Catal. 2019, 9,
422.
2
3
(a) K. Ohkubo, A. Fujimoto, S. Fukuzumi, J. Am. Chem. Soc.
2013, 135, 5368. (b) T. Hering, T. Slanina, A. Hancock, U.
Wille, B. Konig, Chem. Commun. 2015, 51, 6568. (c) H. J. Xu,
X. L. Xu, Y. Fu, Y. S. Feng, Chin. Chem. Lett. 2007, 18, 1471.
(d) J. H. Park, K. C. Ko, E. Kim, N. Park, J. H. Ko, D. H. Ryu, T.
K. Ahn, J. Y. Lee, S. U. Son, Org. Lett. 2012, 14, 5502. (e) S. P.
Pitre, C. D. McTiernan, H. Ismaili, J. C. Scaiano, J. Am. Chem.
Soc. 2013, 135, 13286. (f) D. S. Hamilton, D. A. Nicewicz, J.
Am. Chem. Soc. 2012, 134, 18577. (g) M. Riener, D. A.
Nicewicz, Chem. Sci. 2013, 4, 2625. (h) R. Li, J. Byun, W.
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 7
Green Chemistry
Please do not adjust margins
Journal Name
ARTICLE
17 C. Ye, Y. Zhang, A. Ding, Y. Hu, H, Guo, Sci. Rep. 2018, 8, 2205.
View Article Online
DOI: 10.1039/D0GC02777D
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins