An I2-mediated cascade reaction of 2′-bromoacetophenones with benzohydrazides/benzamides leading to quinazolino[3,2-b]cinnoline or tryptanthrin derivatives

Article abstract of DOI:10.1039/c6ob02699k

An efficient and facile protocol for the synthesis of quinazolinone-fused tetracyclic compounds through an iodine-mediated one-pot cascade reaction of 2′-bromoacetophenones with 2-aminobenzohydrazides or 2-aminobenzamides is reported. With 2-aminobenzohyd

Full text of DOI:10.1039/c6ob02699k

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: S. guo, J. Zhai and
X. Fan, Org. Biomol. Chem., 2017, DOI: 10.1039/C6OB02699K.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
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
author guidelines.
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, outlined
in our author and reviewer resource centre, 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 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 9
View Article Online
DOI: 10.1039/C6OB02699K
Journal Name
ARTICLE
I2‐mediated cascade reaction of 2′‐bromoacetophenones with
benzohydrazides/benzamides leading to quinazolino[3,2‐
b]cinnoline or tryptanthrin derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
Shenghai Guo,* Jianhui Zhai, and Xuesen Fan*
DOI: 10.1039/x0xx00000x
An efficient and facile protocol for the synthesis of quinazolinone‐fused tetracyclic compounds through iodine‐mediated
one‐pot cascade reaction of 2′‐bromoacetophenones with 2‐aminobenzohydrazides or 2‐aminobenzamides is reported.
With 2‐aminobenzohydrazides as the substrates, the reaction gave 5H‐quinazolino[3,2‐b]cinnoline‐7,13‐diones in
moderate to good yields under metal‐catalyst‐free conditions. With 2‐aminobenzamides as the substrates and CuBr as the
catalyst, on the other hand, it afforded tryptanthrin derivatives with good efficiency. Mechanistically, the formation of the
tetracyclic systems is initiated by iodination and oxidation of 2′‐bromoacetophenones followed by a cascade procedure
consisting of cyclocondensation, aromatization and intramolecular cyclization of the in situ formed 2‐bromoarylglyoxals
with 2‐aminobenzohydrazides or 2‐aminobenzamides, respectively.
www.rsc.org/
O
O
O
Introduction
N
N
N
O
N
N
N
H
CO2Me
O
HO
Quinazolinone‐fused tetracyclic compounds, as an
important class of fused nitrogen heterocycles, have drawn
increasing attention in the fields of organic and medicinal
chemistry since they are frequently encountered in various
naturally occurring alkaloids isolated from plant, animal and
microbial sources (Fig. 1),1 and also display significant
antimicrobial,2 anticancer,3 UV‐A protection,4 and DPPH
radical‐scavenging5 activities as well as potent inhibitory
activities6 against NK1 receptor, PDE4, CNS, platelet
aggregation, and TNF‐α. As a result, a number of synthetic
routes have been developed for the construction of different
quinazolinone‐fused tetracyclic derivatives.7 Recently, 2‐
aminobenzohydrazides have been frequently used as versatile
building blocks for the efficient synthesis of novel
quinazolinone‐fused tetracyclic compounds,8 and some of
which exhibit significant bioactivities and blue fluorescent
properties. Therefore, the design and development of practical
and efficient synthetic strategies for the preparation of new
quinazolinone‐fused tetracyclic derivatives with potential
biological activities by using 2‐aminobenzohydrazides as the
starting materials is highly desirable for both organic and
medicinal chemists.
tryptanthrin
phaitanthrin A
phaitanthrin E
HO
OH
O
OH
O
O
N
O
N
N
O
N
O
N
N
NH
NH
N
Me
Ph
OH
(-)-circumdatin I
(-)-2-hydroxycircumdatin C
(-)-benzomalvin A
Fig. 1. Selected naturally occurring alkaloids with quinazolinone‐fused tetracyclic
scaffold.
On the other hand, aryl methyl ketones, which can be easily
converted into more reactive arylglyoxals through
iodination/Kornblum oxidation cascade under I2/DMSO system,
have been widely utilized as arylglyoxal surrogates in the direct
construction of
a large number of pharmacologically
interesting aroyl‐containing heterocycles and natural
products.9 Among them, Wu and co‐workers developed an
efficient methodology for the synthesis of quinazolinone
alkaloids and their analogues through one‐pot cascade
reactions of readily available aryl methyl ketones with 2‐
aminobenzamides.10 Moreover, our recent study has been
focused on the development of new one‐pot cascade reactions
for the preparation of quinazoline‐fused heterocyclic
compounds from readily available starting materials, and some
preliminary results have been successfully achieved.11 Inspired
by the versatile reactivity of 2‐aminobenzohydrazides or aryl
methyl ketones in the construction of quinazolinone‐
containing heterocycles and based on our expertise in this field,
we envisioned that 5H‐quinazolino[3,2‐b]cinnoline‐7,13‐diones,
a novel quinazolinone‐fused tetracyclic compound family,
might be obtained through iodine‐mediated one‐pot cascade
Collaborative Innovation Center of Henan Province for Green Manufacturing of
Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry
of Education, School of Chemistry and Chemical Engineering, Henan Normal
University, Xinxiang, Henan 453007, China. E‐mail: shguo@htu.cn;
xuesen.fan@htu.cn.
Electronic Supplementary Information (ESI) available: Table Sl, X‐ray crystal
structure of 3a (CCDC 1520915), and 1H and 13C NMR spectra of compounds 3a
‐3u,
5a‐5k, 6, and 7. See DOI: 10.1039/x0xx00000x
reaction
of
2′‐bromoacetophenone
with
2‐
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 9
ARTICLE
Journal Name
Table 1. Screening the reaction conditions for the synthesis of 3aa
DOI: 10.1039/C6OB02699K
aminobenzohydrazide derivatives involving a cascade process
including iodination, Kornblum oxidation, cyclocondensation,
aromatization, and intramolecular cyclization (Scheme 1).
View Article Online
Entry
I2 (equiv.)
1a (equiv.)
Base (equiv.)
Yield(%)b
1
1.0
0.2
0.5
0.8
1.3
1.2
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.0
1.0
1.0
1.0
1.0
1.2
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.0)
K2CO3 (3.6)
K2CO3 (4.5)
Na2CO3 (4.5)
NaHCO3 (4.5)
K3PO4 (4.5)
Cs2CO3 (4.5)
DBU (4.5)
68
24
35
45
65
72
78
34
30
38
68
61
nd
78
69
Scheme 1. Designed one‐pot cascade reaction leading to 5H‐quinazolino[3,2‐
b]cinnoline‐7,13‐dione.
2
3
4
Results and discussion
5
To test the feasibility of our designed synthetic route toward
5H‐quinazolino[3,2‐b]cinnoline‐7,13‐dione as shown in Scheme
1, 2′‐bromoacetophenone 1a (0.4 mmol) was firstly treated
with iodine (0.4 mmol) in DMSO at 110 oC. TLC analysis
indicated that 1a was consumed completely in 3 h to provide
6
7
8
9
2‐bromophenylglyoxal.
Then,
N′‐phenyl‐2‐
10
11
12
13
14
15
aminobenzohydrazide 2a (0.4 mmol) and K2CO3 (1.2 mmol)
were added into the reaction vessel. After being stirred at
room temperature for 5 h, the resulting mixture was heated to
o
100 C for another 6 h. Gratifyingly, the designed synthetic
DABCO (4.5)
K2CO3 (4.0)
K2CO3 (3.0)
route worked very well, and the expected 5‐phenyl‐5H‐
quinazolino[3,2‐b]cinnoline‐7,13‐dione (3a) was obtained in a
total yield of 68% (Table 1, entry 1). The structure of 3a was
unambiguously confirmed by X‐ray diffraction analysis (Fig. 2).
To improve the efficiency, the reaction conditions were then
screened, and the results are shown in Table 1. First, the effect
of the dosage of iodine on this reaction was investigated
(Table 1, entries 1‐5), and we found that decreasing or
increasing iodine loading from 1.0 equivalent resulted in
decreased yields of 3a. In addition, it is noted that increasing
the amount of both iodine and 1a from 1.0 to 1.5 equivalents
afforded 3a in the highest yield of 78% (Table 1, entry 7). Next,
several other inorganic and organic bases including Na2CO3,
NaHCO3, K3PO4, Cs2CO3, DBU, and DABCO were tried, however,
all of them were less efficient than K2CO3 (Table 1, entries 8‐13
vs 7). Finally, we also attempted to optimize the amount of
K2CO3, and it was observed that 4.0 equivalents of K2CO3
turned out to provide the same outcome as 4.5 equivalents of
K2CO3 (Table 1, entries 14‐15 vs 7). Therefore, the optimal
reaction conditions are as follows: 1) 1a (1.5 equiv.) was
treated with I2 (1.5 equiv.) in DMSO at 110 oC for 3 h; 2) to the
mixture were added 2a (1.0 equiv) and K2CO3 (4.0 equiv.), and
then stirred at room temperature for 5 h; 3) the resulting
mixture was stirred at 100 oC for another 6 h to afford 3a in 78%
yield (Table 1, entry 14).
aThe reactions were run with (1) 1a, I2, DMSO, 110 oC, 3 h; (2) 2a (0.4 mmol), base,
rt (5 h)~100 oC (6 h). b Isolated yield is reported based on 2a; nd = not detected.
Fig. 2. The crystal structure of product 3a.
Cl, F, and CF3) on the phenyl moiety at different positions took
part in this reaction smoothly to yield the desired 5H‐
quinazolino[3,2‐b]cinnoline‐7,13‐diones 3b‐3f in moderate to
good yields. With 1‐(1‐bromonaphthalen‐2‐yl)ethanone and 1‐
(3‐bromothiophen‐2‐yl)ethanone as reactants, the reaction
could also afford the corresponding products 3g and 3h in 55%
and 53% isolated yields, respectively. Then, the scope of 2‐
aminobenzohydrazide derivatives (
2) was investigated, and we
With the optimized reaction conditions in hand, the scope
and generality of this one‐pot cascade synthesis of 5H‐
found that substrates ( ) bearing a methyl, methoxy, fluoro, or
chloro group at the 4‐position of N′‐phenyl ring were all
2
quinazolino[3,2‐b]cinnoline‐7,13‐diones
(
3
)
were then
compatible with the optimal conditions to deliver the products
investigated and the representative results are demonstrated
3i‐3q in 35%‐76% yields. When N′‐isopropyl substituted
in Table 2. First, the reactions of different 2′‐
benzohydrazide was used, the desired product 3r was not
obtained. Finally, the reaction of N'‐phenyl‐2‐amino‐4‐
chlorobenzohydrazide with three different methyl ketone
bromoacetophenone derivatives
aminobenzohydrazide (2a) were run. The results indicated that
substituted 2′‐bromoacetophenones ( ) with either electron‐
(
1)
with N′‐phenyl‐2‐
1
substrates (
products 3s
1) was also studied, and the corresponding
3u were obtained in 58%‐70% yields.
donating or electron‐withdrawing groups (such as: CH3, CH3O,
‐
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 9
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
View Article Online
DOI: 10.1039/C6OB02699K
Table 2. Scope for the synthesis of 5H‐quinazolino[3,2‐b]cinnoline‐7,13‐dione
derivatives (3)a,b
Scheme 2. Envisioned one‐pot cascade synthesis of tryptanthrin.
(
5a), but yielded 2‐(2‐bromobenzoyl)quinazolin‐4(3H)‐one (6)
in 50% yield (Scheme 3, eq 1). In following studies, it was
observed that the presence of a copper catalyst14 could help to
realize the requisite intramolecular N‐arylation reaction of 6 to
3a, 78%/52%c
3b, 56%
3e, 45%
3h, 53%
3c, 36%
3f, 41%
3i, 66%
give 5a. After thorough screening with regard to different
copper catalysts and bases,15 we found that 5a could be
obtained in a yield of 71% from the one‐pot reaction of 1a and
4a by using CuBr (0.2 equiv) as the catalyst and K2CO3 (4.0
equiv) as the base (Scheme 3, eq 2).
3d, 72%
3g, 55%
3j, 65%
Scheme 3. Attempts for the cascade synthesis of tryptanthrin 5a from 1a and 4a.
3k, 76%
3l, 61%
Next, the substrate scope of 2′‐bromoacetophenone
derivatives (
studied. As shown in Table 3, 2′‐bromoacetophenone
derivatives ( ) bearing a Me, MeO, F, or Cl group on the phenyl
moiety reacted very well with 2‐aminobenzamides (4a) to
provide the corresponding tryptanthrins 5b 5e in 41%‐58%
yields. In addition, the effect of different substituents (R3)
attached to the phenyl unit of benzamides ( ) on this reaction
1) and 2‐aminobenzamide derivatives (4) was then
1
3m, 63%
3n, 60%
3o, 53%
Cl
Cl
‐
O
O
N
O
N
N
N
4
N
OCH3
N
were then investigated. It turned out that 5‐methyl substituted
benzamide is superior to other substituted counterparts (5f vs
3r, not obtained
O
3q, 35%
3p, 70%
5j
‐
5k) in this I2‐mediated tryptanthrin formation reaction.
To explore the reaction mechanisms for the formation of
quinazolinone‐fused tetracyclic products (3a) and (5a), the
following control experiments were then performed as
demonstrated in Scheme 4. First, the mixture of 1a and I2 in
3u, 67%
3t, 58%
3s, 70%
a Reaction conditions: (1) 1 (0.6 mmol), I2 (0.6 mmol), DMSO (3 mL), 110 oC, 3 h;
DMSO at 110 oC for
3
h
was treated with 2‐
(2) 2 (0.4 mmol), K2CO3 (1.6 mmol), rt (5 h)~100 oC (6 h). Isolated yields are
b
aminobenzohydrazide 2a and K2CO3 at room temperature for 5
reported based on 2. c 2'‐Iodoacetophenone was used.
h. And then the resulting mixtrue was stirred at 60 oC for 2 h to
afford intermediate
intermediate with K2CO3 (2.0 equiv.) in DMSO at 100 C for
40 min could provide the final product 3a in 90% yield.
Meanwhile, the intramolecular N‐arylation reaction of could
also proceed smoothly in the presence of TEMPO (1.0 equiv.)
as a radical scavenger to afford the product 3a in 85% yield,
which might rule out the possibility of a radical pathway16 in
7 in 88% yield. Next, treatment of
Having established a novel synthesis of 5H‐quinazolino[3,2‐
o
7
b]cinnoline‐7,13‐diones
(
3)
from the reaction of 2′‐
bromoacetophenones with 2‐aminobenzohydrazides, we were
then interested in whether the present protocol could be
utilized in the synthesis of the biologically and
pharmaceutically significant tryptanthrin derivatives (Fig 1)12,13
7
by
replacing
2‐aminobenzohydrazides
with
2‐
the formation of 3a from
aminobenzamide 4a as reactant, the silimar cascade reaction
could yield the corresponding intermediate in 81% yield.
Subsequently, treatment of intermediate with CuBr (0.2
7 (Scheme 4, eq 1). Second, with 2‐
aminobenzamides (Scheme 2).
To check this hypothesis, 1a was firstly treated with I2 in
o
6
DMSO at 110 C for 3 h. Then, 2‐aminobenzamide (4a) was
6
added into the same vessel under the optimized reaction
conditions for the preparation of 3a (Table 1, entry 14).
Unfortunately, it failed to generate the desired tryptanthrin
o
equiv.) and K2CO3 (2.0 equiv.) in DMSO at 100 C for 40 min
gave rise to tryptanthrin 5a in 73% yield (Scheme 4, eq 2).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 9
ARTICLE
Journal Name
Conclusions
View Article Online
DOI: 10.1039/C6OB02699K
Table 3. Scope for the synthesis of tryptanthrin derivatives (5)a,b
In summary, we have established a practical and efficient
method for the preparation of 5H‐quinazolino[3,2‐b]cinnoline‐
7,13‐dione and tryptanthrin derivatives through iodine‐
mediated one‐pot reaction of 2′‐bromoacetophenones with 2‐
aminobenzohydrazides or 2‐aminobenzamides. The cascade
reaction
of
2′‐bromoacetophenones
with
2‐
aminobenzohydrazides gave rise to 5H‐quinazolino[3,2‐
b]cinnoline‐7,13‐diones as brand‐new quinazolinone‐fused
tetracyclic products in moderate to good yields. On the other
hand, when 2‐aminobenzamides was used to replace 2‐
aminobenzohydrazides as reactants, this present protocol
provided an altermative synthetic route toward tryptanthrin
derivatives under the catalysis of CuBr. The present protocol
has the advantages of easy‐to‐obtain starting materials, good
functional tolerance, diversity of products, and operational
simplicity.
5a, 71%
5d, 42%
5c, 41%
5f, 75%
5b, 58%
5e, 53%
5i, 61%
5g, 68%
5j, 56%
5h, 44%
5k, 54%
Experimental Section
General
a Reaction conditions: (1) 1 (0.6 mmol), I2 (0.6 mmol), DMSO (3 mL), 110 oC, 3 h;
(2) 4 (0.4 mmol), CuBr (0.08 mmol), K2CO3 (1.6 mmol), rt (5 h)~100 oC (3 h). b
Isolated yields are reported based on 4.
Unless noted, all commercial reagents and solvents were used
without further purification. Melting points were recorded
with a micro melting point apparatus and uncorrected. The 1H
NMR spectra were recorded at 400 or 600 MHz. The 13C NMR
spectra were recorded at 100 or 150 MHz. High‐resolution
mass spectra (HRMS) were collected in ESI mode by using a
MicrOTOF mass spectrometer. All reactions were monitored
by thin‐layer chromatography (TLC) using silica gel plates (silica
gel 60 F254 0.25 mm) and components were visualized by
observation under UV light (254 and 365 nm).
General procedure for the preparation of 5H‐quinazolino[3,2‐
b]cinnoline‐7,13‐dione derivatives (3)
Scheme 4. Control experiments.
To a mixture of 2′‐bromoacetophenone
1 (0.6 mmol) in DMSO
On the basis of the above results, plausible mechanisms for
the formation of 3a and 5a are outlined in Scheme 5. First, the
iodination and subsequent Kornblum oxidation of 2′‐
bromoacetophenone 1a under I2/DMSO system afford the
reactive intermediate 2‐bromophenylglyoxal. Second, the
cyclocondensation and aromatization10 of 2‐bromophenyl‐
glyoxal with 2a or 4a deliver the corresponding quinazolinone
(3 mL) was added I2 (0.6 mmol) at room temperature and then
the mixture was stirred at 110 oC for 3 h. Next, 2‐
aminobenzohydrazide
2 (0.4 mmol) and K2CO3 (1.6 mmol)
were added into the reaction vessel at room temperature.
After being stirred at room temperature for 5 h, the resulting
o
mixture was heated to 100 C for another 6 h. Finally, the
reaction was quenched with NH4Cl solution and extracted with
dichloromethane (DCM). The combined organic layer was
washed with H2O and brine, and then dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure and
the crude product was purified by column chromatography on
silica gel to afford 5H‐quinazolino[3,2‐b]cinnoline‐7,13‐dione 3.
intermediate
7 or 6. With the assistance of K2CO3, 7 undergoes
an intramolecular nucleophilic aromatic substitution (SNAr)
reaction to give rise to product 3a. On the other hand, with the
use of CuBr as catalyst and K2CO3 as base, 5a could be
obtained via intramolecular C‐N cross‐coupling reaction of 6.
5‐Phenyl‐5H‐quinazolino[3,2‐b]cinnoline‐7,13‐dione (3a).
Petroleum ether/ethyl acetate (2:1) as eluent; yellow solid (106
mg, 78%), mp 245‐247 oC. 1H NMR (CDCl3, 600 MHz) δ 7.29 (t, J
= 7.2 Hz, 1H), 7.33 (t, J = 7.2 Hz, 1H), 7.37‐7.41 (m, 3H), 7.44 (d,
J = 7.8 Hz, 2H), 7.58 (t, J = 7.8 Hz, 1H), 7.63‐7.66 (m, 1H), 7.85 (t,
J = 7.8 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 7.8 Hz, 1H),
8.27 (d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 121.6,
122.7, 123.5, 125.1, 126.4, 127.2, 127.8, 128.4, 129.0, 129.6,
Scheme 5. Plausible mechanisms for the formation of 3a and 5a.
4 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 9
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
134.9, 136.4, 144.0, 145.4, 146.5, 148.4, 157.7, 175.0 (one 13
ARTICLE
C
15‐Phenyl‐7
H‐benzo[h]quinazolino[3,2‐b]cinnoline‐
View Article Online
DOI: 10.1039/C6OB02699K
signal was not observed). HRMS (ESI) calcd for C21H13N3O2Na 7,13(15 )‐dione (3g). Petroleum ether/ethyl acetate (2:1) as
H
[M + Na]+ 362.0900, found 362.0910.
3‐Methyl‐5‐phenyl‐5 ‐quinazolino[3,2‐b]cinnoline‐7,13‐
eluent; yellow solid (85 mg, 55%), mp 232‐234 C. H NMR
(CDCl3, 600 MHz) δ 7.12 (t, J = 7.2 Hz, 1H), 7.22 (t, J = 7.8 Hz,
o
1
H
dione (3b). Petroleum ether/ethyl acetate (2:1) as eluent; 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.61‐7.70 (m, 3H), 7.86 (t, J = 7.8
yellow solid (79 mg, 56%), mp 246‐248 oC. 1H NMR (CDCl3, 600 Hz, 1H), 7.92 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 7.8 Hz, 1H), 8.13 (d,
MHz) δ 2.40 (s, 3H), 7.14 (d, J = 8.4 Hz, 1H), 7.18 (s, 1H), 7.30 (t, J = 8.4 Hz, 1H), 8.45 (d, J = 7.8 Hz, 1H), 8.67 (d, J = 8.4 Hz, 1H);
J = 7.8 Hz, 1H), 7.39 (t, J = 7.8 Hz, 2H), 7.44 (d, J = 7.8 Hz, 2H), 13C NMR (CDCl3, 150 MHz) δ 121.8, 122.7, 123.5, 126.07,
7.57 (t, J = 7.2 Hz, 1H), 7.84 (t, J = 7.2 Hz, 1H), 8.09 (d, J = 7.8 Hz, 126.11, 127.0, 127.2, 127.5, 128.1, 128.2, 128.5, 129.4, 129.6,
1H), 8.12 (d, J = 8.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H); 13C NMR 129.8, 130.4, 135.0, 137.3, 145.6, 146.5, 146.8, 149.2, 158.9,
(CDCl3, 150 MHz) δ 22.4, 121.37, 121.40, 122.6, 126.5, 126.8, 177.1. HRMS (ESI) calcd for C25H16N3O2 [M + H]+ 390.1237,
127.1, 127.7, 128.3, 128.8, 129.6, 134.8, 144.1, 145.5, 146.7, found 390.1231.
148.3, 148.5, 157.7, 174.6 (one 13C signal was not observed).
4‐Phenyl‐4H‐thieno[3',2':3,4]pyridazino[6,1‐b]quinazoline‐
HRMS (ESI) calcd for C22H15N3O2Na [M + Na]+ 376.1056, found 6,12‐dione (3h). Petroleum ether/ethyl acetate (1:1) as eluent;
376.1062.
yellow solid (73 mg, 53%), mp 273‐275 oC. 1H NMR (CDCl3, 600
MHz) δ 6.83 (d, J = 5.4 Hz, 1H), 7.37‐7.40 (m, 1H), 7.41‐7.43 (m,
2‐Methoxy‐5‐phenyl‐5H‐quinazolino[3,2‐b]cinnoline‐7,13‐
dione (3c). Petroleum ether/ethyl acetate (2:1) as eluent; 2H), 7.45‐7.47 (m, 2H), 7.57 (t, J = 7.2 Hz, 1H), 7.80 (d, J = 5.4
yellow solid (53 mg, 36%), mp 254‐256 oC. 1H NMR (CDCl3, 600 Hz, 1H), 7.87 (t, J = 7.2 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.21 (d,
MHz) δ 3.90 (s, 3H), 7.24‐7.27 (m, 2H), 7.35‐7.39 (m, 5H), 7.56 J = 7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 119.9, 120.7, 121.7,
(d, J = 3.0 Hz, 1H), 7.58 (t, J = 7.2 Hz, 1H), 7.86 (t, J = 7.8 Hz, 1H), 125.2, 127.0, 128.6, 129.0, 129.4, 129.8, 135.0, 139.0, 142.5,
8.10 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 144.7, 145.5, 153.8, 157.5, 167.2. HRMS (ESI) calcd for
150 MHz) δ 56.0, 107.0, 122.5, 123.8, 124.6, 125.7, 126.6, C19H12N3O2S [M + H]+ 346.0645, found 346.0642.
127.2, 128.1, 128.9, 129.59, 129.61, 134.9, 143.0, 143.9, 145.5,
5‐(p‐Tolyl)‐5H‐quinazolino[3,2‐b]cinnoline‐7,13‐dione (3i).
147.0, 157.0, 157.7, 174.9. HRMS (ESI) calcd for C22H16N3O3 [M Petroleum ether/ethyl acetate (2:1) as eluent; yellow solid (93
+ H]+ 370.1186, found 370.1185.
3‐Chloro‐5‐phenyl‐5 ‐quinazolino[3,2‐b]cinnoline‐7,13‐
mg, 66%), mp 194‐196 oC. 1H NMR (CDCl3, 600 MHz) δ 2.32 (s,
3H), 7.18 (d, J = 7.8 Hz, 2H), 7.30 (t, J = 7.8 Hz, 1H), 7.34‐7.37
H
dione (3d). Petroleum ether/ethyl acetate (2:1) as eluent; (m, 3H), 7.57 (t, J = 7.2 Hz, 1H), 7.63 (t, J = 8.4 Hz, 1H), 7.85 (t, J
o
1
yellow solid (108 mg, 72%), mp 260‐262 C. H NMR (CDCl3, = 7.8 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.22 (d, J = 7.8 Hz, 1H),
600 MHz) δ 7.26‐7.28 (m, 1H), 7.33‐7.36 (m, 2H), 7.41‐7.44 (m, 8.27 (d, J = 8.4 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 21.1, 121.3,
2H), 7.46‐7.47 (m, 2H), 7.59 (t, J = 7.2 Hz, 1H), 7.86 (t, J = 7.2 Hz, 122.7, 123.1, 124.8, 126.6, 127.1, 127.7, 128.9, 129.6, 130.2,
1H), 8.10 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 134.8, 136.4, 138.6, 143.86, 143.88, 145.4, 148.7, 157.6, 174.9.
7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 121.0, 121.4, 122.6, HRMS (ESI) calcd for C22H16N3O2 [M + H]+ 354.1237, found
125.9, 126.8, 127.2, 128.9, 129.1, 129.3, 129.7, 129.8, 135.0, 354.1240.
143.1, 143.4, 145.3, 145.7, 149.0, 157.4, 173.9. HRMS (ESI)
3‐Methyl‐5‐(p‐tolyl)‐5H‐quinazolino[3,2‐b]cinnoline‐7,13‐
calcd for C21H12ClN3O2Na [M + Na]+ 396.0510, found 396.0505.
dione (3j). Petroleum ether/ethyl acetate (2:1) as eluent;
2‐Fluoro‐5‐phenyl‐5H‐quinazolino[3,2‐b]cinnoline‐7,13‐
yellow solid (96 mg, 65%), mp 187‐189 oC. 1H NMR (CDCl3, 600
dione (3e). Petroleum ether/ethyl acetate (2:1) as eluent; MHz) δ 2.32 (s, 3H), 2.39 (s, 3H), 7.11 (d, J = 8.4 Hz, 1H), 7.13 (s,
yellow solid (64 mg, 45%), mp 212‐214 oC. 1H NMR (CDCl3, 400 1H), 7.18 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 7.8 Hz, 2H), 7.56 (t, J =
MHz) δ 7.27‐7.32 (m, 1H), 7.35‐7.44 (m, 6H), 7.58‐7.62 (m, 1H), 7.8 Hz, 1H), 7.84 (t, J = 7.2 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.11
7.84‐7.89 (m, 2H), 8.10 (d, J = 8.0 Hz, 1H), 8.28 (dd, J = 1.2, 8.0 (d, J = 7.8 Hz, 1H), 8.26 (d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 150
Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 112.6 (d, J = 23.0 Hz, 1C), MHz) δ 21.1, 22.4, 121.0, 121.1, 122.6, 126.5, 126.7, 127.1,
122.7, 124.4 (d, J = 7.7 Hz, 1C), 124.76 (d, J = 7.7 Hz, 1C), 127.6, 128.7, 129.5, 130.2, 134.8, 138.6, 143.97, 144.01, 145.5,
124.80 (d, J = 25.1 Hz, 1C), 126.1, 127.2, 128.5, 129.2, 129.7, 148.3, 148.8, 157.7, 174.5. HRMS (ESI) calcd for C23H18N3O2 [M
129.8, 135.0, 143.4, 145.0, 145.4, 146.6, 157.6, 159.5 (d, J = + H]+ 368.1394, found 368.1385.
247.2 Hz, 1C), 174.4. HRMS (ESI) calcd for C21H13FN3O2 [M + H]+
358.0986, found 358.0971.
3‐Chloro‐5‐(
p‐tolyl)‐5H‐quinazolino[3,2‐b]cinnoline‐7,13‐
dione (3k). Petroleum ether/ethyl acetate (2:1) as eluent;
yellow solid (118 mg, 76%), mp 266‐268 C. H NMR (CDCl3,
o
1
5‐Phenyl‐2‐(trifluoromethyl)‐5
H
‐quinazolino[3,2‐
b
]cinnoline‐7,13‐dione (3f): Petroleum ether/ethyl acetate 600 MHz) δ 2.34 (s, 3H), 7.21 (d, J = 7.8 Hz, 2H), 7.24 (m, 1H),
o
1
(2:1) as eluent; yellow solid (67 mg, 41%), mp 244‐246 C. H 7.32 (s, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.57 (t, J = 7.8 Hz, 1H), 7.85
NMR (CDCl3, 600 MHz) δ 7.37 (t, J = 7.2 Hz, 1H), 7.43‐7.44 (m, (t, J = 8.4 Hz, 1H ), 8.09 (d, J = 7.8 Hz, 1H), 8.17 (d, J = 8.4 Hz,
3H), 7.50‐7.51 (m, 2H), 7.59 (t, J = 7.8 Hz, 1H), 7.80 (d, J = 9.0 1H), 8.25 (d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 21.1,
Hz, 1H), 7.87 (t, J = 7.8 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.24 (d, 120.8, 121.1, 122.7, 125.6, 126.9, 127.1, 129.0, 129.2, 129.6,
J = 7.8 Hz, 1H), 8.52 (s, 1H); 13C NMR (CDCl3, 150 MHz) δ 121.6, 130.4, 134.9, 139.2, 143.0, 143.1, 143.3, 145.3, 149.3, 157.4,
121.8, 122.7, 123.2 (q, J = 271.2 Hz, 1C), 125.6 (q, J = 4.5 Hz, 173.9. HRMS (ESI) calcd for C22H14ClN3O2Na [M + Na]+ 410.0667,
1C), 126.9 (q, J = 33.9 Hz, 1C), 127.1, 127.3, 129.2, 129.3, 129.7, found 410.0668.
129.8, 132.4 (q, J = 2.1 Hz, 1C), 135.1, 142.8, 145.1, 145.2,
5‐(4‐Methoxyphenyl)‐5H‐quinazolino[3,2‐b]cinnoline‐7,13‐
dione (3l). Petroleum ether/ethyl acetate (2:1) as eluent;
150.2, 157.3, 173.7. MS (ESI) m/z 408 [M+H]+.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 9
ARTICLE
Journal Name
yellow solid (90 mg, 61%), mp 215‐217 oC. 1H NMR (CDCl3, 600 7.34 (m, 5H), 7.56 (d, J = 3.0 Hz, 1H), 7.60 (t, J = 7.2 Hz, 1H),
View Article Online
DOI: 10.1039/C6OB02699K
MHz) δ 3.77 (s, 3H), 6.88 (d, J = 9.0 Hz, 2H), 7.28‐7.30 (m, 2H), 7.86 (t, J = 7.8 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 7.8
7.42 (d, J = 9.0 Hz, 2H), 7.57 (t, J = 7.2 Hz, 1H), 7.60‐7.63 (m, Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 56.0, 107.2, 122.4, 123.7,
1H), 7.83‐7.86 (m, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.22‐8.23 (m, 124.7, 126.6, 127.1, 127.2, 129.1, 129.7, 129.8, 133.9, 135.0,
1H), 8.27 (d, J = 8.4 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 55.5, 142.5, 143.7, 145.5, 157.2, 157.7, 174.8 (one 13C signal was not
114.6, 121.3, 122.7, 122.9, 124.6, 127.1, 127.6, 128.76, 128.83, observed). HRMS (ESI) calcd for C22H14ClN3O3Na [M + Na]+
129.6, 134.8, 136.4, 138.8, 143.7, 145.4, 149.1, 157.6, 159.4, 426.0616, found 426.0595.
174.8. HRMS (ESI) calcd for C22H16N3O3 [M + H]+ 370.1186,
found 370.1189.
10‐Chloro‐5‐phenyl‐5
dione (3s). Petroleum ether/ethyl acetate (2:1) as eluent;
yellow solid (104 mg, 70%), mp 264‐266 C. H NMR (CDCl3,
H‐quinazolino[3,2‐b]cinnoline‐7,13‐
o
1
3‐Chloro‐5‐(4‐methoxyphenyl)‐5
H
‐quinazolino[3,2‐
b
]cinnoline‐7,13‐dione (3m). Petroleum ether/ethyl acetate 600 MHz) δ 7.30‐7.35 (m, 2H), 7.38‐7.41 (m, 3H), 7.43‐7.44 (m,
(2:1) as eluent; yellow solid (102 mg, 63%), mp 220‐222 oC. 1H 2H), 7.65 (t, J = 7.2 Hz, 1H), 7.78 (dd, J = 1.8, 8.4 Hz, 1H), 8.04
NMR (CDCl3, 600 MHz) δ 3.79 (s, 3H), 6.91 (d, J = 9.0 Hz, 2H), (d, J = 9.0 Hz, 1H), 8.22‐8.23 (m, 2H); 13C NMR (CDCl3, 150 MHz)
7.23‐7.25 (m, 2H), 7.42 (d, J = 9.0 Hz, 2H), 7.58 (t, J = 7.2 Hz, δ 121.5, 123.3, 123.6, 125.2, 126.5, 127.8, 128.6, 129.7, 131.2,
1H), 7.85 (t, J = 7.2 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 135.1, 135.5, 136.5, 143.9, 144.0, 146.3, 148.3, 156.6, 174.6
9.0 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H); 13C NMR (CDCl3, 150 MHz) (one 13C signal was not observed). HRMS (ESI) calcd for
δ 55.5, 114.8, 120.7, 120.9, 122.7, 125.5, 127.1, 128.97, 129.01, C21H12ClN3O2Na [M + Na]+ 396.0510, found 396.0501.
129.1, 129.6, 134.9, 137.9, 143.0, 143.2, 145.3, 149.6, 157.4,
159.7, 173.8. HRMS (ESI) calcd for C22H14ClN3O3Na [M + Na]+
426.0616, found 426.0587.
10‐Chloro‐3‐methyl‐5‐phenyl‐5
]cinnoline‐7,13‐dione (3t). Petroleum ether/ethyl acetate
(2:1) as eluent; yellow solid (90 mg, 58%), mp 232‐233 C. H
NMR (CDCl3, 600 MHz) δ 2.40 (s, 3H), 7.14‐7.16 (m, 2H), 7.31 (t,
H‐quinazolino[3,2‐
b
o
1
5‐(4‐Fluorophenyl)‐5H‐quinazolino[3,2‐b]cinnoline‐7,13‐
dione (3n). Petroleum ether/ethyl acetate (2:1) as eluent; J = 7.2 Hz, 1H), 7.39 (t, J = 7.8 Hz, 2H), 7.43‐7.44 (m, 2H), 7.77
yellow solid (86 mg, 60%), mp 208‐210 oC. 1H NMR (CDCl3, 600 (dd, J = 1.8, 8.4 Hz, 1H), 8.03 (d, J = 9.0 Hz, 1H), 8.12 (d, J = 7.8
MHz) δ 7.07 (t, J = 8.4 Hz, 2H), 7.29‐7.34 (m, 2H), 7.47‐7.49 (m, Hz, 1H), 8.22 (d, J = 2.4 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ
2H), 7.59 (t, J = 7.2 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.86 (t, J = 22.4, 121.22, 121.24, 123.6, 126.5, 126.6, 126.9, 127.7, 128.5,
7.8 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 7.8 Hz, 1H), 8.27 129.6, 131.1, 135.0, 135.4, 143.9, 144.1, 146.4, 148.4, 148.5,
(d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 116.5 (d, J = 156.7, 174.2. HRMS (ESI) calcd for C22H14ClN3O2Na [M + Na]+
23.0 Hz, 2C), 121.4, 122.6, 123.2, 125.1, 127.1, 127.8, 129.05, 410.0667, found 410.0660.
129.11 (d, J = 9.9 Hz, 2C), 129.6, 135.0, 136.5, 142.2 (d, J = 3.3
3,10‐Dichloro‐5‐phenyl‐5H‐quinazolino[3,2‐b]cinnoline‐
Hz, 1C), 143.6, 145.4, 148.4, 157.6, 161.9 (d, J = 248.4 Hz, 1C), 7,13‐dione (3u). Petroleum ether/ethyl acetate (2:1) as eluent;
o
1
174.7. HRMS (ESI) calcd for C21H13FN3O2 [M + H]+ 358.0986, yellow solid (109 mg, 67%), mp 269‐270 C. H NMR (CDCl3,
found 358.0970.
5‐(4‐Fluorophenyl)‐3‐methyl‐5H‐quinazolino[3,2‐
600 MHz) δ 7.28 (d, J = 8.4 Hz, 1H), 7.34 (s, 1H), 7.36 (t, J = 7.2
Hz, 1H), 7.42‐7.46 (m, 4H), 7.78 (dd, J = 1.8, 9.0 Hz, 1H), 8.03 (d,
b
]cinnoline‐7,13‐dione (3o). Petroleum ether/ethyl acetate J = 9.0 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 1.8 Hz, 1H);
o
1
(2:1) as eluent; yellow solid (79 mg, 53%), mp 258‐260 C. H 13C NMR (CDCl3, 150 MHz) δ 120.9, 121.2, 123.6, 126.0, 126.5,
NMR (CDCl3, 600 MHz) δ 2.40 (s, 3H), 7.06‐7.09 (m, 3H), 7.14 (d, 126.9, 129.1, 129.3, 129.9, 131.2, 135.3, 135.6, 143.3, 143.4,
J = 8.4 Hz, 1H), 7.46‐7.49 (m, 2H), 7.58 (t, J = 7.8 Hz, 1H), 7.85 (t, 143.8, 145.5, 148.9, 156.4, 173.6. HRMS (ESI) calcd for
J = 7.2 Hz, 1H), 8.09 (d, J = 7.8 Hz, 1H), 8.13 (d, J = 7.8 Hz, 1H), C21H11Cl2N3O2Na [M + Na]+ 430.0121, found 430.0120.
8.26 (d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 22.4, 116.5
General procedure for the preparation of tryptanthrin derivatives
(5)
(d, J = 23.0 Hz, 2C), 121.1, 121.2, 122.6, 126.8, 127.1, 127.7,
128.9, 129.2 (d, J = 8.9 Hz, 2C), 129.6, 134.9, 142.3 (d, J = 3.3
Hz, 1C), 143.8, 145.4, 148.4, 148.6, 157.7, 161.1, 174.3. HRMS To a mixture of 2′‐bromoacetophenone
1 (0.6 mmol) in DMSO
(ESI) calcd for C22H15FN3O2 [M + H]+ 372.1143, found 372.1144.
5‐(4‐Chlorophenyl)‐5 ‐quinazolino[3,2‐ ]cinnoline‐7,13‐
(3 mL) was added I2 (0.6 mmol) at room temperature and then
H
b
the mixture was stirred at 110 oC for 3 h. Next, 2‐
dione (3p). Petroleum ether/ethyl acetate (2:1) as eluent; aminobenzamide
yellow solid (105 mg, 70%), mp 229‐231 C. H NMR (CDCl3, (1.6 mmol) were added into the reaction vessel at room
600 MHz) δ 7.34‐7.36 (m, 4H), 7.39‐7.40 (m, 2H), 7.60 (t, J = temperature. After being stirred at room temperature for 5 h,
4 (0.4 mmol), CuBr (0.08 mmol), and K2CO3
o
1
o
7.2 Hz, 1H), 7.66 (t, J = 8.4 Hz, 1H), 7.87 (t, J = 7.2 Hz, 1H), 8.10 the resulting mixture was heated to 100 C for another 3 h.
(d, J = 8.4 Hz, 1H), 8.23 (d, J = 7.8 Hz, 1H), 8.28 (d, J = 7.8 Hz, Finally, the reaction was quenched with NH4Cl solution and
1H); 13C NMR (CDCl3, 150 MHz) δ 121.5, 122.6, 123.6, 125.4, extracted with dichloromethane (DCM). The combined organic
127.1, 127.89, 127.91, 129.2, 129.7, 129.8, 134.3, 135.0, 136.5, layer was washed with H2O and brine, and then dried over
143.8, 144.9, 145.4, 148.0, 157.6, 174.8. HRMS (ESI) calcd for anhydrous Na2SO4. The solvent was removed under reduced
C21H13ClN3O2 [M + H]+ 374.0691, found 374.0699.
5‐(4‐Chlorophenyl)‐2‐methoxy‐5 ‐quinazolino[3,2‐
]cinnoline‐7,13‐dione (3q). Petroleum ether/ethyl acetate
pressure and the crude product was purified by column
H
chromatography on silica gel to afford tryptanthrin 5.
b
Indolo[2,1‐
b
]quinazoline‐6,12‐dione (5a)12a
.
Petroleum
o
1
(2:1) as eluent; yellow solid (56 mg, 35%), mp 245‐247 C. H ether/ethyl acetate (3:1) as eluent; yellow solid (70 mg, 71%),
NMR (CDCl3, 600 MHz) δ 3.91 (s, 3H), 7.25‐7.27 (m, 1H), 7.30‐ mp 267‐269 oC. 1H NMR (CDCl3, 400 MHz) δ 7.40 (t, J = 7.6 Hz,
6 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 9
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
1H), 7.62‐7.66 (m, 1H), 7.73‐7.77 (m, 1H), 7.82 (dt, J = 1.2, 8.0 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.91 (d, J = 8.4 HzV,i1ewHA)r,ti8cl.e2O2nl(inse,
Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H), 8.38 1H), 8.46 (s, 1H); 13C NMR (CDCl3, 150 MHz) δ 21.7, 23.0, 118.5,
DOI: 10.1039/C6OB02699K
(dd, J = 1.2, 8.0 Hz, 1H), 8.57 (d, J = 8.4 Hz, 1H); 13C NMR (CDCl3, 120.0, 123.5, 125.2, 127.3, 128.0, 130.5, 136.4, 141.1, 144.3,
100 MHz) δ 117.9, 121.9, 123.7, 125.4, 127.2, 127.5, 130.2, 144.6, 146.7, 150.7, 158.2, 182.0. HRMS (ESI) calcd for
130.7, 135.1, 138.2, 144.3, 146.3, 146.5, 158.0, 182.5. MS (ESI) C17H12N2O2Na [M + Na]+ 299.0791, found 299.0789.
m/z 249 [M+H]+.
9‐Fluoro‐2‐methylindolo[2,1‐b]quinazoline‐6,12‐dione (5h).
9‐Methylindolo[2,1‐b]quinazoline‐6,12‐dione
(5b). Petroleum ether/ethyl acetate (2:1) as eluent; yellow solid (49
Petroleum ether/ethyl acetate (3:1) as eluent; yellow solid (61 mg, 44%), mp 296‐298 oC. 1H NMR (CDCl3, 400 MHz) δ 2.57 (s,
mg, 58%), mp 205‐207 oC. 1H NMR (CDCl3, 400 MHz) δ 2.49 (s, 3H), 7.41 (dd, J = 2.0, 8.0 Hz, 1H), 7.68 (dd, J = 1.6, 8.0 Hz, 1H),
3H), 7.16 (d, J = 7.6 Hz, 1H), 7.59‐7.63 (m, 1H), 7.73 (d, J = 7.6 7.84 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 8.23 (s, 1H),
Hz, 1H), 7.78 (dt, J = 1.6, 8.0 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 8.69 (d, J = 1.6 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 21.7, 106.6
8.37 (dd, J = 1.2, 8.0 Hz, 1H), 8.40 (s, 1H); 13C NMR (CDCl3, 150 (d, J = 28.4 Hz, 1C), 114.6 (d, J = 24.0 Hz, 1C), 118.6 (d, J = 2.3
MHz) δ 23.0, 118.5, 119.8, 123.7, 125.3, 127.5, 128.0, 130.1, Hz, 1C), 123.2, 127.5, 127.7 (d, J = 11.0 Hz, 1C), 130.7, 136.7,
130.6, 135.1, 144.9, 146.68, 146.72, 150.8, 158.2, 182.0. HRMS 141.5, 143.8, 144.4, 148.0 (d, J = 14.3 Hz, 1C), 158.0, 168.4 (d, J
(ESI) calcd for C16H10N2O2Na [M + Na]+ 285.0634, found = 259.2 Hz, 1C), 180.8. HRMS (ESI) calcd for C16H9FN2O2Na [M +
285.0654.
8‐Methoxyindolo[2,1‐
Na]+ 303.0540, found 303.0537.
9‐Chloro‐2‐methylindolo[2,1‐b]quinazoline‐6,12‐dione (5i).
b
]quinazoline‐6,12‐dione
(5c)12f
.
Petroleum ether/ethyl acetate (3:1) as eluent; red solid (46 mg, Petroleum ether/ethyl acetate (3:1) as eluent; yellow solid (72
41%), mp 234‐236 oC. 1H NMR (CDCl3, 400 MHz) δ 3.91 (s, 3H), mg, 61%), mp 222‐223 oC. 1H NMR (CDCl3, 400 MHz) δ 2.57 (s,
7.32 (dd, J = 2.8, 8.8 Hz, 1H), 7.39 (d, J = 2.8 Hz, 1H), 7.66‐7.70 3H), 7.11 (dt, J = 2.4, 8.4 Hz, 1H), 7.67 (dd, J = 1.6, 8.4 Hz, 1H),
(m, 1H), 7.85 (dt, J = 1.6, 8.0 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.91‐7.95 (m, 2H), 8.22 (s, 1H), 8.37 (dd, J = 2.0, 8.8 Hz, 1H); 13
C
8.44 (dd, J = 1.2, 8.0 Hz, 1H), 8.53 (d, J = 8.8 Hz, 1H); 13C NMR NMR (CDCl3, 150 MHz) δ 21.7, 118.6, 120.4, 123.2, 126.2,
(CDCl3, 100 MHz) δ 56.0, 108.4, 119.1, 123.0, 123.9, 125.0, 127.5, 127.6, 130.7, 136.7, 141.6, 143.6, 144.4, 144.6, 146.8,
127.4, 130.2, 130.7, 134.9, 140.4, 144.8, 146.6, 157.7, 158.7, 158.0, 181.3. HRMS (ESI) calcd for C16H9ClN2O2Na [M + Na]+
182.7. MS (ESI) m/z 279 [M+H]+.
9‐Fluoroindolo[2,1‐ ]quinazoline‐6,12‐dione
319.0245, found 319.0283.
2‐Methoxyindolo[2,1‐ ]quinazoline‐6,12‐dione
b
(5d).
b
(5j).
Petroleum ether/ethyl acetate (2:1) as eluent; yellow solid (45 Petroleum ether/ethyl acetate (2:1) as eluent; yellow solid (62
mg, 42%), mp 240‐242 oC. 1H NMR (CDCl3, 400 MHz) δ 7.05 (dt, mg, 56%), mp 282‐284 oC. 1H NMR (CDCl3, 600 MHz) δ 3.99 (s,
J = 2.4, 8.4 Hz, 1H), 7.61‐7.65 (m, 1H), 7.81 (dt, J = 1.6, 8.0 Hz, 3H), 7.40‐7.44 (m, 2H), 7.77‐7.80 (m, 1H), 7.83 (d, J = 2.4 Hz,
1H), 7.86‐7.90 (m, 1H), 7.97 (d, J = 7.6 Hz, 1H), 8.30 (dd, J = 2.0, 1H), 7.91 (d, J = 7.2 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H), 8.63 (d, J =
8.8 Hz, 1H), 8.37 (dd, J = 1.2, 8.0 Hz, 1H); 13C NMR (CDCl3, 150 7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 56.1, 108.3, 118.0,
MHz) δ 106.7 (d, J = 28.5 Hz, 1C), 114.7 (d, J = 24.0 Hz, 1C), 122.4, 124.3, 125.2, 125.3, 127.2, 132.4, 138.0, 140.9, 142.6,
118.5, 123.5, 127.7, 127.8 (d, J = 10.8 Hz, 1C), 130.5, 130.8, 146.2, 157.9, 161.4, 182.5. HRMS (ESI) calcd for C16H10N2O3Na
135.4, 144.4, 146.5, 148.1 (d, J = 13.1 Hz, 1C), 158.0, 168.5 (d, J [M + Na]+ 301.0584, found 301.0595.
= 260.3 Hz, 1C), 180.8. HRMS (ESI) calcd for C15H7FN2O2Na [M +
3‐Chloroindolo[2,1‐
b
]quinazoline‐6,12‐dione
(5k).
Na]+ 289.0384, found 289.0388.
Petroleum ether/ethyl acetate (2:1) as eluent; yellow solid (61
9‐Chloroindolo[2,1‐
b
]quinazoline‐6,12‐dione
(5e)13e
.
mg, 54%), mp 248‐250 oC. 1H NMR (CDCl3, 600 MHz) δ 7.45 (t, J
Petroleum ether/ethyl acetate (3:1) as eluent; yellow solid (60 = 7.2 Hz, 1H), 7.63 (dd, J = 1.8, 8.4 Hz, 1H), 7.79‐7.81 (m, 1H),
mg, 53%), mp 237‐239 oC. 1H NMR (CDCl3, 400 MHz) δ 7.35 (dd, 7.92 (d, J = 7.2 Hz, 1H), 8.00 (d, J = 1.8 Hz, 1H), 8.37 (d, J = 8.4
J = 2.0, 8.4 Hz, 1H), 7.62‐7.66 (m, 1H), 7.78‐7.83 (m, 2H), 7.97‐ Hz, 1H), 8.61 (d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ
7.99 (m, 1H), 8.38 (dd, J = 1.2, 8.0 Hz, 1H), 8.63 (d, J = 1.6 Hz, 118.0, 121.8, 122.2, 125.6, 127.5, 128.8, 130.1, 130.7, 138.5,
1H); 13C NMR (CDCl3, 150 MHz) δ 118.6, 120.3, 123.5, 126.3, 141.5, 145.3, 146.2, 147.7, 157.5, 182.2. HRMS (ESI) calcd for
127.67, 127.71, 130.5, 130.9, 135.4, 144.2, 144.7, 146.5, 146.8, C15H7ClN2O2Na [M + Na]+ 305.0088, found 305.0094.
158.0, 181.2. MS (ESI) m/z 283 [M+H]+.
2‐Methylindolo[2,1‐ ]quinazoline‐6,12‐dione
2‐(2‐Bromobenzoyl)quinazolin‐4(3
ether/ethyl acetate (3:1) as eluent; yellow solid (107 mg, 81%),
H)‐one (6). Petroleum
b
(5f)12f
.
Petroleum ether/ethyl acetate (3:1) as eluent; yellow solid (79 mp 206‐207 oC. 1H NMR (CDCl3, 600 MHz) δ 7.44‐7.50 (m, 2H),
mg, 75%), mp 225‐227 oC. 1H NMR (CDCl3, 400 MHz) δ 2.55 (s, 7.63‐7.65 (m, 2H), 7.70 (dd, J = 1.2, 8.4 Hz, 1H), 7.77‐7.82 (m,
3H), 7.41 (t, J = 7.6 Hz, 1H), 7.65 (dd, J = 2.0, 8.4 Hz, 1H), 7.77 2H), 8.39 (dd, J = 0.6, 7.8 Hz, 1H), 9.95 (brs, 1H); 13C NMR
(dt, J = 1.2, 8.0 Hz, 1H), 7.89‐7.92 (m, 2H), 8.21 (d, J = 0.8 Hz, (CDCl3, 150 MHz) δ 121.0, 123.4, 126.9, 127.0, 129.6, 129.8,
1H), 8.61 (d, J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.7, 130.9, 132.7, 133.5, 134.9, 136.6, 145.2, 147.6, 160.6, 189.3.
118.0, 122.1, 123.5, 125.3, 127.1, 127.3, 130.6, 136.4, 138.1, HRMS (ESI) calcd for C15H9BrN2O2Na [M + Na]+ 350.9740, found
141.3, 143.7, 144.6, 146.3, 158.1, 182.6. MS (ESI) m/z 263 350.9750.
[M+H]+.
2,9‐Dimethylindolo[2,1‐
2‐(2‐Bromobenzoyl)‐3‐(phenylamino)quinazolin‐4(3
H)‐one
b
]quinazoline‐6,12‐dione
(5g). (7). Petroleum ether/ethyl acetate (2:1) as eluent; white solid
o
1
Petroleum ether/ethyl acetate (2:1) as eluent; yellow solid (75 (147 mg, 88%), mp 203‐205 C. H NMR (CDCl3, 600 MHz) δ
mg, 68%), mp 203‐205 oC. 1H NMR (CDCl3, 400 MHz) δ 2.55 (s, 6.84 (s, 1H), 6.86 (d, J = 8.4 Hz, 2H), 6.99 (t, J = 7.2 Hz, 1H), 7.23
3H), 2.56 (s, 3H), 7.21 (d, J = 7.6 Hz, 1H), 7.65 (dd, J = 1.6, 8.0 (t, J = 7.8 Hz, 2H), 7.40‐7.45 (m, 2H), 7.58 (t, J = 7.8 Hz, 1H),
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 7
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 8 of 9
ARTICLE
Journal Name
X.‐F. Wu, Org. Biomol. Chem., 2015, 13, 4422‐4425; (d) Y.‐Y.
7.64 (d, J = 7.2 Hz, 1H), 7.80‐7.86 (m, 2H), 7.97 (d, J = 7.2 Hz,
1H), 8.31 (d, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 150 MHz) δ 115.1,
122.4, 122.8, 123.2, 127.2, 127.7, 128.1, 128.4, 129.1, 132.7,
134.5, 134.6, 135.1, 135.2, 145.0, 147.1, 153.1, 160.9, 186.2.
HRMS (ESI) calcd for C21H15BrN3O2 [M + H]+ 420.0342, found
420.0338.
View Article Online
Han, H. Jiang, R. Wang and S. Yu, J. DOOrIg: .10C.1h0e3m9/.C,62O0B1062,69891K
7276‐7281; (e) V. N. Murthy, S. P. Nikumbh, S. P. Kumar, Y.
Chiranjeevi, L. V. Rao and A. Raghunadh, Synlett, 2016, 27
,
,
2362‐2367; (f) T. Földesi, A. Dancsó, G. Simig, B. Volk and M.
Milen, Tetrahedron, 2015, 71, 6759‐6763; (g) J. A. Bleda, P.
M. Fresneda, R. Orenes and P. Molina, Eur. J. Org. Chem.,
2009, 2490‐2504; (h) A. D. Roy, A. Subramanian, B.
Mukhopadhyay and R. Roy. Tetrahedron Lett., 2006, 47
,
6857‐6860; (i) M. Mahdavi, R. Najafi, M. Saeedi, E. Alipour, A.
Shafiee and A. Foroumadi, Helv. Chim. Acta, 2013, 96, 419‐
423.
Acknowledgements
We thank the National Natural Science Foundation of China
(Grants 21202040 and 21572047), Project Funded by China
Postdoctoral Science Foundation (2014M552007 and
2015T80771), and the Program for Innovative Research Team
in Science and Technology in University of Henan Province
(15IRTSTHN003) for financial support.
8
(a) R.‐Z. Jin, W.‐T. Zhang, Y.‐J. Zhou and X.‐S. Wang,
Tetrahedron Lett., 2016, 57, 2515‐2519; (b) Z. Arasteh‐Fard,
K. A. Dilmaghani, M. Saeedi, M. Mahdavi and A. Shafiee, Helv.
Chim. Acta, 2016, 99, 539‐542; (c) Y.‐G. Ma, C. Li, C.‐S. Yao
and X.‐S. Wang, Tetrahedron, 2016, 72, 3844‐3850; (d) D.‐S.
Chen, G.‐L. Dou, Y.‐L. Li, Y. Liu and X.‐S. Wang, J. Org. Chem.,
2013, 78, 5700‐5704; (e) W. Yang, R. Qiao, J. Chen, X. Huang,
M. Liu, W. Gao, J. Ding and H. Wu, J. Org. Chem., 2015, 80
,
482‐489; (f) W. Yang, J. Chen, X. Huang, J. Ding, M. Liu and H.
Wu, Org. Lett., 2014, 16, 5418‐5421; (g) W.‐T. Zhang, W.‐W.
Notes and references
Qiang, C.‐S. Yao and X.‐S. Wang, Tetrahedron, 2016, 72
,
1
(a) U. A. Kshirsagar, Org. Biomol. Chem., 2015, 13, 9336‐9352;
(b) M. Demeunynck and I. Baussanne, Curr. Med. Chem.,
2013, 20, 794‐814; (c) S. B. Mhaske and N. P. Argade,
Tetrahedron, 2006, 62, 9787‐9826; (d) J. P. Michael, Nat.
Prod. Rep., 2007, 24, 223‐246; (e) J. P. Michael, Nat. Prod.
Rep., 2005, 22, 627‐646; (f) J. P. Michael, Nat. Prod. Rep.,
2004, 21, 650‐668.
2178‐2185; (h) W.‐T. Zhang, D.‐S. Chen, M.‐M. Zhang and X.‐
S. Wang, Res. Chem. Intermed., 2016, 42, 6769‐6776; (i) N. T.
Patil, P. G. V. V. Lakshmi, B. Sridhar, S. Patra, M. Pal Bhadra
and C. R. Patra, Eur. J. Org. Chem., 2012, 1790‐1799.
9
(a) H.‐Z. Li, W.‐J. Xue and A.‐X. Wu, Tetrahedron, 2014, 70
4645‐4651 and references cited therein; (b) Y.‐P. Zhu, M.‐C.
Liu, Q. Cai, F.‐C. Jia and A.‐X. Wu, Chem. Eur. J., 2013, 19
,
,
2
3
(a) P. P. Bandekar, K. A. Roopnarine, V. J. Parekh, T. R.
Mitchell, M. J. Novak and R. R. Sinden, J. Med. Chem., 2010,
53, 3558‐3565; (b) S. K. Pandey, A. Singh and A. Nizamuddin,
Eur. J. Med. Chem., 2009, 44, 1188‐1197.
10132‐10137; (c) W.‐J. Xue, Y.‐Q. Guo, F.‐F. Gao, H.‐Z. Li and
A.‐X. Wu, Org. Lett., 2013, 15, 890‐893; (d) Q. Gao, S. Liu, X.
Wu and A. Wu, Org. Lett., 2014, 16, 4582‐4585; (e) Q. Gao, J.
Zhang, X. Wu, S. Liu and A. Wu, Org. Lett., 2015, 17, 134‐137;
(f) X. Wu, Q. Gao, X. Geng, J. Zhang, Y.‐D. Wu and A.‐X. Wu,
Org. Lett., 2016, 18, 2507‐2510; (g) J.‐C. Xiang, Y. Cheng, M.
Wang, Y.‐D. Wu and A.‐X. Wu, Org. Lett., 2016, 18, 4360‐
4363; (h) J. Zhang, Q. Gao, X. Wu, X. Geng, Y.‐D. Wu and A.
Wu, Org. Lett., 2016, 18, 1686‐1689.
(a) V. M. Sharma, P. Prasanna, K. V. Adi Seshu, B. Renuka, C.
V. Laxman Rao, G. Sunil Kumar, C. Prasad Narasimhulu, P.
Aravind Babu, R. C. Puranik, D. Subramanyam, A.
Venkateswarlu, S. Rajagopal, K. B. Sunil Kumar, C. Seshagiri
Rao, N. V. S. Rao Mamidi, D. S. Deevi, R. Ajaykumar and R.
Rajagopalan, Bioorg. Med. Chem. Lett., 2002, 12, 2303–2307;
(b) C.‐W. Jao, W.‐C. Lin, Y.‐T. Wu and P.‐L. Wu, J. Nat. Prod.,
2008, 71, 1275‐1279; (c) S. Venkateswarlu, M. Satyanarayana,
V. Lakshmikanthan and V. Siddaiah, J. Heterocycl. Chem.,
2015, 52, 1631‐1638; (d) C. J. Thomas, N. J. Rahier and S. M.
Hecht, Bioorg. Med. Chem., 2004, 12, 1585‐1604; (e) V. A.
Rao, K. Agama, S. Holbeck and Y. Pommier, Cancer Res., 2007,
67, 9971‐9979.
10 Y.‐P. Zhu, Z. Fei, M.‐C. Liu, F.‐C. Jia and A.‐X. Wu, Org. Lett.,
2013, 15, 378‐381.
11 (a) S. Guo, J. Wang, X. Fan, X. Zhang and D. Guo, J. Org.
Chem., 2013, 78, 3262‐3270; (b) X.‐Y. Zhang, X.‐J. Guo and X.‐
S. Fan, Chem. Asian J., 2015, 10, 106‐111; (c) S. Guo, L. Tao,
W. Zhang, X. Zhang and X. Fan, J. Org. Chem., 2015, 80
10955‐10964; (d) S. Guo, Y. Li, L. Tao, W. Zhang and X. Fan,
RSC Adv., 2014, , 59289‐59296.
,
4
4
5
6
D. Zhang, X. Yang, J. S. Kang, H. D. Choi and B. W. Son, J.
Antibiot., 2008, 61, 40‐42.
C.‐M. Cui, X.‐M. Li, C.‐S. Li, H.‐F. Sun, S.‐S. Gao and B.‐G.
Wang, Helv. Chim. Acta, 2009, 92, 1366‐1370.
12 For selected synthetic routes toward tryptanthrin derivatives,
see: (a) F.‐C. Jia, Z.‐W. Zhou, C. Xu, Y.‐D. Wu and A.‐X. Wu,
Org. Lett., 2016, 18, 2942‐2945; (b) M. A. Ali El‐Remaily and
O. M. Elhady, Tetrahedron Lett., 2016, 57, 435‐437; (c) B. V. S.
Reddy, D. M. Reddy, G. N. Reddy, M. R. Reddy and V. K.
Reddy, Eur. J. Org. Chem., 2015, 8018‐8022; (d) T. Abe, T.
Itoh, T. Choshi, S. Hibino and M. Ishikura, Tetrahedron Lett.,
2014, 55, 5268‐5270; (e) S. D. Vaidya and N. P. Argade, Org.
Lett., 2013, 15, 4006‐4009; (f) C. Wang, L. Zhang, A. Ren, P.
Lu and Y. Wang, Org. Lett., 2013, 15, 2982‐2985.
(a) H. H. Sun, C. J. Barrow, D. M. Sedlock, A. M. Gillum and R.
Cooper, J. Antibiot., 1994, 47, 515‐522; (b) K. Siva Kumar, P.
Mahesh Kumar, V. Sreenivasa Rao, A. A. Jafar, C. L. T. Meda,
R. Kapavarapu, K. V. L. Parsa and M. Pal, Org. Biomol. Chem.,
2012, 10, 3098‐3103; (c) G. E. Hardtmann and B. Huegi, J.
Med. Chem., 1971, 14, 878‐882; (d) F. Ishikawa, H.
Yamaguchi, J. Saegusa, K. Inamura, T. Mimura, T. Nishi, K.
Sakuma and S.‐I. Ashida, Chem. Pharm. Bull., 1985, 33, 3336‐
3348; (e) K. Siva Kumar, P. Mahesh Kumar, K. Anil Kumar, M.
Sreenivasulu, A. A. Jafar, D. Rambabu, G. Rama Krishna, C.
Malla Reddy, R. Kapavarapu, K. Shivakumar, K. Krishna Priya,
K. V. L. Parsa and M. Pal, Chem. Commun., 2011, 47, 5010‐
5012.
13 For the biological activites of tryptanthrin derivatives, see: (a)
G. Honda and M. Tabata, Planta Med., 1979, 36, 85‐86; (b) S.
Yang, X. Li, F. Hu, Y. Li, Y. Yang, J. Yan, C. Kuang and Q. Yang, J.
Med. Chem., 2013, 56, 8321‐8331; (c) J. L. Liang, S.‐E. Park, Y.
Kwon and Y. Jahng, Bioorg. Med. Chem., 2012, 20, 4962‐4967;
(d) K. Seya, A. Yamaya, S. Kamachi, M. Murakami, H.
Kitahara, J. Kawakami, K. Okumura, M. Murakami, S.
Motomura and K.‐I. Furukawa, J. Nat. Prod., 2014, 77, 1413‐
1419; (e) J.‐M. Hwang, T. Oh, T. Kaneko, A. M. Upton, S. G.
7
For selected examples, see: (a) I. Khan, A. Ibrar, W. Ahmed
and A. Saeed, Eur. J. Med. Chem., 2015, 90, 124‐169 and
references cited therein; (b) H. Li, W. Li, A. Spannenberg, W.
Baumann, H. Neumann, M. Beller and X.‐F. Wu, Chem. Eur. J.,
2014, 20, 8541‐8544; (c) C. Shen, N. Y. Man, S. Stewart and
Franzblau, Z. Ma, S.‐N. Cho and P. Kim, J. Nat. Prod., 2013, 76
354‐367; (f) A. K. Bhattacharjee, D. J. Skanchy, B. Jennings, T.
,
8 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 9
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
H. Hudson, J. J. Brendle and K. A. Werbovetz, Bioorg. Med.
Chem., 2002, 10, 1979‐1989; (g) B. Hou, Y. Ai, C. Wang, N.
Zhang, L. Yang, Z. Liu and J. Liu, Chin. J. Org. Chem., 2016, 36
121‐129.
View Article Online
DOI: 10.1039/C6OB02699K
,
14 For selected copper‐catalyzed intramolecular N‐arylation
reactions, see: (a) Y. Liu and J.‐P. Wan, Org. Biomol. Chem.,
2011, 9, 6873‐6894; (b) Y.‐H. Jhan, T.‐W. Kang and J.‐C. Hsieh,
Tetrahedron Lett., 2013, 54, 1155‐1159; (c) W. Yang, Y. Long,
S. Zhang, Y. Zeng and Q. Cai, Org. Lett., 2013, 15, 3598‐3601;
(d) U. A. Kshirsagar and N. P. Argade, Org. Lett., 2010, 12
,
3716‐3719; (e) M. B. Calvert and J. Sperry, J. Heterocyclic
Chem., 2014, 51, 282‐284; (f) D. Viña, E. del Olmo, J. L. López‐
Pérez and A. S. Feliciano, Org. Lett., 2007, 9, 525‐528; (g) J.
Peng, M. Ye, C. Zong, F. Hu, L. Feng, X. Wang, Y. Wang and C.
Chen, J. Org. Chem., 2011, 76, 716‐719.
15 For details, please see Table S1 in the Supporting
Information.
16 M. Tsujii, M. Sonoda and S. Tanimori, J. Org. Chem., 2016, 81
,
6766‐6773.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 9
Please do not adjust margins