A one-pot construction of acridones by rhodium catalyzed reaction of N-phenyl-2-(1-sulfonyl-1H-1,2,3-triazol-4-yl)aniline

Article abstract of DOI:10.1016/j.tetlet.2015.10.059

A one-pot synthesis of N-alkyl acridone via rhodium catalyzed decomposition of N-phenyl-2-(1-sulfonyl-1H-1,2,3-triazol-4-yl)aniline and subsequent oxidative C–C bond fragmentation has been developed. 14 examples are presented and the yields range from 30% to 80%.

Full text of DOI:10.1016/j.tetlet.2015.10.059

Accepted Manuscript
A one-pot construction of acridones by rhodium catalyzed reaction of N-phe-
nyl-2-(1-sulfonyl-1H-1,2,3-triazol-4-yl)aniline
Hua-Dong Xu, Ying-Peng Pan, Xin-Tao Ren, Ping Zhang, Mei-Hua Shen
PII:
S0040-4039(15)30256-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.10.059
TETL 46888
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 August 2015
14 October 2015
17 October 2015
Please cite this article as: Xu, H-D., Pan, Y-P., Ren, X-T., Zhang, P., Shen, M-H., A one-pot construction of acridones
by rhodium catalyzed reaction of N-phenyl-2-(1-sulfonyl-1H-1,2,3-triazol-4-yl)aniline, Tetrahedron Letters (2015),
doi: http://dx.doi.org/10.1016/j.tetlet.2015.10.059
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Graphical Abstract
A one-pot construction of acridones by
rhodium catalyzed reaction of N-phenyl-2-(1-
sulfonyl-1H-1,2,3-triazol-4-yl)aniline
Leave this area blank for abstract info.
Hua-Dong Xu,* Ying-Peng Pan, Xin-Tao Ren, Ping Zhang and Mei-Hua Shen*
School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu Province
213164, China.

1
Tetrahedron Letters
A one-pot construction of acridones by rhodium catalyzed reaction of N-phenyl-2-(1-
sulfonyl-1H-1,2,3-triazol-4-yl)aniline
Hua-Dong Xu,* Ying-Peng Pan, Xin-Tao Ren, Ping Zhang and Mei-Hua Shen*
School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu Province 213164, China. E-mail: shenmh@cczu.edu.cn, hdxu@cczu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Abstract: A one-pot synthesis of N-alkyl acridone via rhodium catalyzed decomposition of N-
phenyl-2-(1-sulfonyl-1H-1,2,3-triazol-4-yl)aniline and subsequent oxidative C-C bond
fragmentation has been developed. 14 examples are presented and the yields range from 30% to
80%.
Available online
Keywords:
Acridone
N-Sulfonyl 1,2,3-trizaole
Rhodium Carbene
Cyclization
Aza-Vinyl Metal Carbene
Since demonstrated as a viable metal carbene precursor in
2008,1 N-sulfonyl 1,2,3-trizaole has attracted intensive attention
in this respect.2-20 Comparing with probably the most studied
carbene progenitor diazo compounds in organic synthesis, N-
sulfonyl 1,2,3-trizaoles feature some advantages. First, not as the
hazardous and dangerous diazo compounds, triazoles are
relatively more stable and safer for routine handling in
laboratory. Second, it is convenient to prepare N-sulfonyl 1,2,3-
trizaoles from corresponding terminal alkynes in almost neutral
conditions which would facilitate the studies of carbene
chemistry in complex molecule settings. And more, the unique
aza-vinyl metal carbenes generated from triazole compounds
exhibit more diverse reactivities because of potential
participation of α-imino group in reactions.
Miura and Murakami group have discovered that triazole-
derived aza-vinyl rhodium carbenes 2 react with aromatic ring at
6-position leading to tricyclic N-heterocycles 3.21 Our laboratory
and Lin’s laboratory discovered that aza-vinyl rhodium carbenes
5 derived from triazoles 4 cyclize onto anilinyl ring at 5-position
to give bicyclic N-heterocyclic aldehyde 6 upon losing sulfonyl
amine.22,23 Bearing these findings in mind, we are curious what is
the behavior of analogous α-imino carbene 8, which also has an
aromatic π-bond at 6-position; in other words, the reaction of
triazole 7 will give teracycle 9 as the formation of 3 from 1 or
aldehyde 10 following the process of the conversion of triazole 4
to indolyl aldehyde 6. Here we would like to communicate our
findings.
Our study started with triazole 7a. In the presence of catalytic
amount of rhodium acetate, a solution of 7a in toluene was
o
heated to 60 C under nitrogen for 2 hours, and then the reaction
mixture was treated with K2CO3 in methanol under air at room
temperature overnight. To our surprise, acridone 11a was
obtained in 42% isolated yield (Table 1 entry 2). When the
o
reaction temperature was raised to 80 C, the yield increased to
62% (entry 3); whereas enhancement of the temperature to 100
oC didn’t result in further improvement in yield (entry 5). On the
other hand, the sulfonyl triazole starting material can keep intact
o
in 40 C for several hours (entry 1). Replacement of Rh2(OAc)4
with Rh2(esp)2 as catalyst resulted in a reduced yield to 50%
(entry 6). When the first step was also carried out in air, 11a was
obtained in only 43% yield suggesting that the air might act
adversely in the first step reaction (entry 7). Other non-
nucleophilic solvents such as dichloroethane and chloroform are
also feasible for this reaction though giving lower yields (entries
8 and 9). This reaction could proceed smoothly at a 5 mmol scale
showing the potential for its large scale application (entry 4).
Scheme 1. a) Tricycles synthesis from sulfonyl triazoles; b)
indolyl aldehyde synthesis from sulfonyl triazoles; c) question
current research aims to answer.

2
Tetrahedron Letters
Acridones 11b-11e were obtained from corresponding ortho-
Table 1, Condition optimization for one-pot synthesis of N-
methyl acridonea
aminophenyltriazoles 7b-7e in yields increasing from 52% for
electro-deficiently fluorinated 7b to 66% for electro-rich
methoxylated 11e, demonstrating that electro-donating group on
the aromatic ring of the triazole component would facilitate
acridone formation. The relatively low yield of 11f probably
reflects the interference by the nearby alkene group that would
compete for metal carbene. Very interestingly, replacement of the
N-methyl group with N-benzyl group resulted in a dramatically
enhancement of product yield to 80%, presumably due to the
greater steric repulsion caused by the bigger Bn vs Me, which
would push the bulky Rhodium carbene toward the reacting
aniline ring. While the reason accounting for the unexpected low
yield of 11h from 7h was not clear at present stage, the more than
30% divergence in yields between 11i and 11j might reflect the
different nucleophilicity of the aromatic carbon defined by the
methoxyl substitution in 7i and 7j accordingly. It is also worth to
note that the reaction of 7j afforded the para-cyclized product
absolutely and no ortho-cyclized acridone was detected. This
excellent regioselectivity might be a consequence of the steric
repulsion of the meta-methoxyl group toward the bulky rhodium
carbene segment. p-Chlorination on the aniline also afford
product 11c in decreased yield, similar to the effect of p-
cyanation on the yield of 11m. Thermal decomposition of p-
carbonylated phenylamino trizaole 7n gave rise to acridone 11n.
The low yield obtained probably due to an additional O to N acyl
transfer step for the formation of 11n from 7n.
Conditions for first step
atmosphere
Step 1 Step 2
Yieldb
Entry
[Rh](2 mol%)
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(esp)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
T /°C
40
60
80
80
100
80
80
80
1
2
3
4
5
6
7
8
9
N2 air
_
N2
N2
N2
N2
N2
air
N2
N2
air
air
air
air
air
air
air
air
42%
62%
60%c
60%
50%
43%
51%
54%
chloroform
80
a, Unless otherwise specified, the reaction was conducted on a 0.1 mmol
scale b, isolated yield; c, carried out in a 5 mmol scale.
The acridone framework exists widely in nature and has
versatile biological activities.24-26 However there are limited
strategies that could access this class of tricyclic alkaloids.27 The
most common method applies Friedel-Crafts reaction to construct
the middle ring.28-30 Recently, direct oxidative C-H amination
was used to build the middle ring.31 A pretty unique approach
that completes the tricyclic system through a final 6 π -
electrocyclization to make the side ring has also emerged.32 The
current transformation of 7a to 11a provides a new approach to
acridone framework. Accordingly, more substrates were made
and subjected to the optimal conditions to prove the generality of
this method. The results are listed in Table 2.
To gain more information, the residue of the first step, namely
rhodium catalyzed reaction of 7a, was treated with NaBH4 in
methanol. Tosyl amide 12a was isolated in 60% yield
accompanied with 2-hydoxyl tosyl amide 13a in 35% yield.
Table 2. One-pot synthesis of acridone derivativesa
Scheme 2. Direct treatment of the residue of first step with
NaBH4
These data strongly suggested tosyl imine 14a as the direct
product and 15a as the side product of the first step. In second
step, 14a is converted to 11a through oxidative fragmentation in
air.33-35The side product of 13a derived from the reaction of
carbene intermediate 8a with water.36 Reduction of 14a and 15a
with NaBH4 afford 12a and 13a respectively.
Scheme 3. Explanation of the origins for observed products.
In summary, we have demonstrated that N-aryl-2-(1-sulfonyl-
1H-1,2,3-triazol-4-yl)aniline can be converted to acridones
smoothly by a one-pot operation. First step operates through a
rhodium catalyzed decomposition of sulfonyl triazoles to
corresponding rhodium carbene which cyclized with the other N-
aryl group to form Acridanyl sulfonylimine. Subsequent
oxidation with air affords related acridones in useful yields.
a, reactions were conducted on a 0.1 mmol scale; b isolated yields.

3
14.
15.
16.
17.
18.
19.
20.
21.
22.
Tang, X.-Y.; Zhang, Y.-S.; He, L.; Wei, Y.; Shi, M.
Chem. Commun. 2015, 51, 133.
Acknowledgments
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The authors wish to thank the Natural Science Foundation of
China (21402014 and 21272077), the Natural Science
Foundation of Jiangsu Province (BK20131143), the Priority
Academic Program Development of Jiangsu Higher Education
Institutions (PADA), and Jiangsu Key Laboratory of Advanced
Catalytic Materials and Technology (BM2012110).
Supplementary Material
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tet.2015.xx
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