Synthesis of acridones through palladium-catalyzed carbonylative of 2-bromo-diarylamines

Article abstract of DOI:10.1016/j.tetlet.2018.06.004

A facile protocol for the synthesis of acridone derivatives has been developed through palladium-catalyzed carbonylation/C–H activation sequence from 2-bromo-diarylamines in moderate to excellent yields. The reactions occurred smoothly and allowed both el

Full text of DOI:10.1016/j.tetlet.2018.06.004

Accepted Manuscript
Synthesis of acridones through palladium-catalyzed carbonylative of 2-Bromo-
diarylamines
Juan Song, Keran Ding, Wei Sun, Songjiang Wang, Haisen Sun, Kang Xiao,
Yan Qian, Chao Liu
PII:
S0040-4039(18)30731-7
https://doi.org/10.1016/j.tetlet.2018.06.004
TETL 50042
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
31 March 2018
29 May 2018
1 June 2018
Please cite this article as: Song, J., Ding, K., Sun, W., Wang, S., Sun, H., Xiao, K., Qian, Y., Liu, C., Synthesis of
acridones through palladium-catalyzed carbonylative of 2-Bromo-diarylamines, Tetrahedron Letters (2018), doi:
https://doi.org/10.1016/j.tetlet.2018.06.004
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Tetrahedron Letters
Synthesis of acridones through palladium-catalyzed carbonylative of 2-Bromo-
diarylamines
Juan Songa,  , Keran Dinga , Wei Sunb, c , Songjiang Wanga , Haisen Suna , Kang Xiaoa , Yan Qiana and
Chao Liu b, 
aKey Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu
National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023,
P. R. China
bState Key Laboratory for Oxo Synthesis and Selective Oxidation, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese
Academy of Sciences, Lanzhou, 730000, P. R. China
cUniversity of Chinese Academy of Sciences, Beijing, 100049, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A facile protocol for the synthesis of acridone derivatives has been developed through
palladium-catalyzed carbonylation/C-H activation sequence from 2-bromo-diarylamines in
moderate to excellent yields. The reactions occurred smoothly and allowed both electron-rich
and electron-deficient substrates converted to the corresponding acridones.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
carbonylation
C-H activation
1. Introduction
As
a consequence, synthetic methods leading to the
costruction of this scaffold have been continuously refined in
recent decades (Scheme 2). Of these synthetic procedures,
closing central six-membered ring is the key step in most
employed strategies. As shown in Scheme 2, according to
different cyclization approach, the synthetic routes to obtain
acridone can be classified into three types: (1) C-N coupling
(scheme 2, a);20-22 (2) acid-promoted cyclization (Scheme 2, b);23-
Acridone,
a type of distinguished Nitrogen-containing
heterocycle, is omnipresent structural motif that exists in a wide
range of natural products,1-4 biologically or pharmacologically
active compounds5-9 and organic optoelectronics materials.10,11
Especially, with the development of organic semi-conductive
materials during the last four decades, research on acridone-based
organic photoelectric materials has attracted more and more
attention.12-16 For example, DMQA was found to be a high
performance green-sensitive organic photodiode.17 BEdAcC9
was reported as an OLED emitter material by Data and co-
workers.18 TQB was proved to be a good thermally activated
delayed fluorescence (TADF) material (Scheme 1).19
25
(3) CO insertion (Scheme 2, c).26, 27 In general, classical routes
for acridone synthesis are path a (scheme 2) and b (scheme 2) .
However, CO insertion is an more attractive transformation as it
involves the insertion of CO as the cheapest C1 source and meets
the requirements of “atom economy”, step economy and “green
chemistry”. Palladium-catalyzed carbonylation reaction is widely
recognized as a very important tool in industrial and organic
chemistry. In 2015, Jiang firstly described a novel approach to
acridones by CO insertion using arynes generated from silylaryl
triflate precursors.27 Greaney,29 Larock28, 30,31 also reported their
related work in the following years. Recently, Lei’s group
Scheme 1. Representative examples of molecular material
containing acridone.
Reported
a
palladium/copper
co-catalyzed
oxidative
cardonylation of diphenylamines for the construction of
acridones. In this transformation, the oxidant was necessary .26
Herein, we report our newly developed simple approach for the
———
 Corresponding author. e-mail: iamjsong@njupt.edu.cn
 Corresponding author. e-mail: chaoliu@licp.cas.cn

2
Tetrahedron Letters
synthesis of acridone by palladium-catalyzed carbonylative C-
increasing of temperature was adverse to the reaction (Table1,
H arylation under alkaline condition.
entry 11). No better result was found from changing the Pd
source (Table 1, entry 12-13) and base (Tbale1 entry 14-17).
Delightfully, in 2 mL DMF, a 72% isolated yield of 2a was
obtained (Table 1, entry 12) which was higher than that in 1 mL
DMF. Furthermore, if stirring the PdCl2, ligand and CsOPiv in 2
mL DMF at 120 ℃ in advance for 30 minutes before 1a was
added to the system, a slight higher yield (78%) could be
obtained (Table 1, entry 13). Notably, no desired product was
observed for 2-bromo-N-phenylaniline (Table 1, entry 14). The
optimum reaction conditions thus far being developed: 1.0 equiv.
of 2-bromo-N-methyl-N-phenylaniline (1a) (0.2 mmol) was
added to the reaction system after 5 mol% of PdCl2, 10 mol%
PCy3·HBF4 and 3.0 equiv. of CsOPiv were stirred in 2 mL DMF
at 120 °C for 30 minutes. The mixture was then allowed to stir at
120 ℃ for 12 hours before quenched. This procedure provided
acridone 2a in 78% of isolated yield.
Scheme 2. Approaches towards the synthesis of acridone
derivatives
2. Result and discussion
With the optimized conditions established, the substrate scope
of this palladium-catalyzed carbonylation/C-H activation tandem
reaction was evaluated. The results were summarized in Table 2.
Most of employed substrates were well tolerated and proceeded
smoothly to afford their corresponding products in moderate to
excellent yields. In detail, for 2-bromo-N-(4-substituted-phenyl)-
N-methylaniline (Table 2, entries 2-7), substrates bearing
electron-donating groups such as -CH3 (Table 2, entry 2), -
CH(CH3)2 (Table 2, entry 7), -C(CH3)3 (Table 2, entry 3) or
electron-withdrawing groups such as –F (Table 2, entry 5) and –
Cl (Table 2, entry 6) were proceeded smoothly to afford their
corresponding products in good yields. However, the strong
electron donating substituent of –OCH3 gave the product 2d
(Table 2, entry 4) in lower yield of 37% and the yield was
improved to 75% when the reaction time was extended to 60
hours. Moreover, the sterically hindered N-(2-bromophenyl)-
N,3,5-trimethylaniline (1h) also underwent a smooth reaction to
afford the desired product in good yield of 70% (Table 2, entry
Initially, 2-bromo-N-methyl-N-phenylaniline 1a was selected
as the model substrate for optimization in our initial
investigation. As shown in table 1, among the ligands examined,
the use of PCy3·HBF4 resulted in the highest yield (49%) of 2a
(Table 1, entry 1), other ligands such as PPh3 gave the desired
product in lower yield (12% ) (Table 1, entry 2) and no
conversion was observed for P(t-Bu)3·HBF4 (Table 1, entry 3) or
Xantphos (Table 1, entry 4). Then, several solvents were
screened. The use of DMF afforded 2a in comparable yield
(48%) (Table1, entry 5). However, if changing the reaction
medium to DMA, 1,4-dioxane or NMP, no desired product was
obtained (Table 1, entries 6-8). Decreasing the reaction
temperature resulted in lower efficiency in terms of chemical
yield (Table1, entry 9) and the yield of 2a was increased to 59%
at 120 ℃ (Table1, entry 10), but a further
Table 1. Condition Optimization of the Palladium-Catalyzed
carbonylation of 2-Bromo-diarylamines for the Synthesis of
Acridines a
8).
Successively,
2-bromo-4-substituted-N-methyl-N-
phenylaniline (Table 2, entries 9, 11-13) were examined under
the optimized conditions. Differing from 2-bromo-N-(4-
substituted-phenyl)-N-methylanilines, the electronic effects of
the substituents played a great influence on the yield of
corresponding product. The electron-rich substrates (1i)
obviously worked better than electron-deficient substrates (1k,
1l, 1m), and 2-bromo-N,5-dimethyl-N-phenylaniline (1j) gave
better result than 2-bromo-N,4-dimethyl-N-phenylaniline (1i).
Moreover, interestingly, 4,N-dimethyl-2-bromoanilin (1i)
afforded a slightly higher yield than 2-bromo-N-methyl-N-(p-
tolyl)aniline
phenylaniline
(1b),
(1k)
while
and
2-bromo-4-fluoro-N-methyl-N-
2-bromo-4-chloro-N-methyl-N-
phenylaniline (1l) produced 2e and 2f in the yields of 37% and
29% respectively which were dramatically lower than that of 2-
bromo-N-(4-fluorophenyl)-N-methylaniline (1e) or 2-bromo-N-
(4-chlorophenyl)-N-methylaniline (1f). In addition, to further
evaluate the scope of the reaction, N-CH3 was changed to N-
C2H5, N-Bn, N-Ph and so on (Table 2, entries 14-20). All
compounds were reacted smoothly and transformed to the
corresponding products (2n-2t) in moderate to good yield.
Among them, the long-chain-alkyl substrate (1p) gave the
product 2p in the lowest yield of 45%. For 2-bromo-4-
substituted-N,N-diphenylaniline (1s, 1t), it was also found that
the 2-bromo-4-methyl-N,N-diphenylaniline (1s) afforded the
product 2s in higher yield than 2-bromo-4-fluoro-N,N-
diphenylaniline (1t). This was in accordance with the previous
studies for 2-bromo-4-substituted-N-methyl-N-phenylaniline
which showing that the electron-rich substrates worked better
than electron-deficient substrates.
As shown in Scheme 3, the mechanism for this tranformation
was postulated based on the earlier reports on palladium
catalyzed carbonylation reaction.32-35 Initially, as the precursors
of Pd(0) complex, PdCl2 was readily reduced to Pd(0) by

reducing agents such as CO, phosphines ligand or DMF. Then,
oxidative addition of substrate 1 to Pd(0) to afford the
arylpalladium species A, which followed by insertion of the the
coordinated CO into the C−Pd bond to produce the acylpalladium
intermediate B. In the presence of base, a intramolecular
cyclization via C-H activation occurred for intermediate B to
convert into intermediate C. At last, reductive elimination of
intermediate C afforded the product 2 with simultaneous
regeneration of the Pd(0) catalyst.
Table 2. Palladium-catalyzed carbonylation of 2-bromo-diphenylamines: scope and limitationa
Scheme 3. The proposed reaction mechanism

4
Tetrahedron
21. Kazuhiro, K.; Kazuhiro, N.; Shohei, Y.; Toshihide, K. Helv. Chim. Acta.
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In summary, a facile protocol for the synthesis of acridone
derivatives has been developed through palladium-catalyzed
carbonylation/C-H activation sequence using 2-bromo-
diphenylamines as substrates. The reactions occurred smoothly
and allowed both electron-rich and electron-deficient substrates
converted to the corresponding acridones in moderate to
excellent yields. This reaction afforded an alternative approach
for the synthesis of acridones.
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Acknowledgments
This work was supported by the National Natural Science
Foundation of China (21673261, 21603245, 21703265 and
21573111), Key Laboratory of Organic Synthesis of Jiangsu
Province (KJS1747), the Funding from Nanjing University of
Posts and Telecommunications (NY217072, NY215016,
NY215079).
Supplementary Material
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic
file. That file can then be transformed into PDF format and
submitted along with the manuscript and graphic files to the
appropriate editorial office.
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Graphical Abstract
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Synthesis of Acridones through Palladium-
catalyzed Carbonylative of 2-Bromo-
diarylamines
Leave this area blank for abstract info.
Juan Songa,*, Keran Dinga, Wei Sunb, Songjiang Wanga, Haisen Suna, Kang Xiaoa, Yan Qiana and Chao Liub,*

6
Tetrahedron
Highlights



Simple and efficient protocol for the synthesis of
acridone derivatives.
Reaction proceeds
carbonylation of 2-bromo-diarylamines
Reaction feature broad substrate scope and good
functional group tolerance.
via
palladium-catalyzed