Pd/C-Catalyzed Aminocarbonylation of Aryl Iodides with Anthranils in Water Using Mo(CO)6 as the CO Source

Article abstract of DOI:10.1002/chem.201703994

A convenient procedure for the synthesis of N-(2-carbonylaryl)benzamides has been developed. Through Pd/C-catalyzed aminocarbonylation of anthranils with various hindered and functionalized aryl iodides, the desired amides were afforded in moderate to good yields. The protocol is advantageous due to the recyclable Pd/C catalyst, safe Mo(CO)₆ as the solid CO source, and environmentally benign water as solvent. No inert atmosphere protection is needed.

Full text of DOI:10.1002/chem.201703994

A Journal of
Accepted Article
Title: Pd/C-Catalysed Aminocarbonylation of Aryl Iodides with
Anthranils in Water Using Mo(CO)6 as the CO Source
Authors: Xiao-Feng Wu, Zechao Wang, and Zhiping Yin
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To be cited as: Chem. Eur. J. 10.1002/chem.201703994
Link to VoR: http://dx.doi.org/10.1002/chem.201703994
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10.1002/chem.201703994
Chemistry - A European Journal
COMMUNICATION
Pd/C-Catalyzed Aminocarbonylation of Aryl Iodides with
Anthranils in Water Using Mo(CO)6 as the CO Source
Zechao Wang,a Zhiping Yin,a and Xiao-Feng Wu*[a]
Abstract: A convenient procedure for the synthesis of N-(2-
carbonylaryl)benzamides has been developed. Through
achievements, and also based on our continual interests in
carbonylation chemistry, we become interested in using
anthranil as nitrogen source in aminocarbonylation. Herein, we
wish to report our new results on aminocarbonylation of aryl
iodides with anthranils for the synthesis of N-(2-
carbonylaryl)benzamides. With Pd/C as a recyclable catalyst,
Pd/C−catalyzed aminocarbonylation of anthranils with various
hindered and functionalized aryl iodides, the desired amides were
afforded in moderate to good yields. The protocol is advantageous
due to the recyclable Pd/C catalyst, safe Mo(CO)6 as the solid CO
source, and environmentally benign water as solvent. No inert
atmosphere protection is needed.
17
using Mo(CO)6 as the solid and safe CO source, and water as
the green solvent, the desired amides were formed in good
yields. Additionally, the reactions were carried out under air; no
inert atmosphere protection is needed.
Transition-metal-catalyzed aminocarbonylation is an interesting
and important chemical transformation method for the direct
synthesis of aromatic amides via coupling of aryl, heteroaryl, or
alkynyl halides with amines, which are important building blocks
for various natural products and designed pharmaceutical
molecules.1 Some heterocyclic amides are reported as the
potential CNS (central nervous system)-active compounds.2
Table 1 Optimization of the reaction conditions.a
Therefore,
a large numbers of methods toward amides
synthesize have been developed. Since the first report on
palladium-catalyzed aminocarbonylation of aryl halides with
carbon monoxide from Heck and Schoenberg in 1974,3 this
transformation has been studied by different groups with various
homogeneous palladium catalysts,4-8 such as PdX2(PPh3)2,3
b
Entry
Base
Additive
Yield[%]
1
2
3
4
5
6
7
8
9
Cs2CO3
Et3N
DBU
DABCO
DIPEA
Et3N
Et3N
Et3N
Et3N
−
−
−
−
−
16
42
trace
trace
37
62
56
49
58
51
33
73
44
83 (81)
76
Pd(dppp)Cl2,5
Pd(OAc)2/DCPP
(DCPP
=
1,3−bis(dicyclohexylphosphino)propane),6 Pd(OAc)2/xantphos,7
and Pd(OAc)2/PPh3 catalytic system.8 Concerning the nitrogen
partners applied in aminocarbonylation reactions, mostly
amines,9 but also amides,10 and even organo nitro compounds11
have all been studied.
TBAB
TBAC
TBAHS
TBAB (5 mol %)
TBAB (10 mol %)
TBAB
Anthranil, a class of benzo fused heterocycle, contains a
N-O bond in the ring, has been applied as reagent in nickel-
catalysed cross-coupling with organozinc reagents and ring
expansion reactions with aryldiazoacetates.12 More recently,
anthranils have used it as nitrogen source by many research
groups.13-16 Hashmi and co-workers studied the C-H annulation
of anthranil derivatives with alkynes to produce unprotected 7-
acylindoles with gold as the catalyst.13 Meanwhile, Li’s group14
and Jiao’s group15 studied the applied of anthranils as N source
in various C-H activation reactions, respectively. Various of
amides were produced in good yields. Tiwari and co-workers
developed a novel copper-catalyzed synthesis of functionalized
quinolines from the ketones and anthranils with aza-Michael
addition as the key step.16 Inspired by these interesting
10
11
12
Et3N
Et3N (1 equiv.)
Et3N (3 equiv.)
Et3N (3 equiv.)
Et3N (3 equiv.)
Et3N (3 equiv.)
TBAB
TBAB
TBAB
TBAB
c
13
14
15
d
e
a
Reaction conditions: 1a (0.3 mmol, 1 equiv.), 2a (0.75 mmol, 2.5 equiv.), Pd/C
(3.2 mg, 10 mol %), Mo(CO)6 (0.3 mmol, 1 equiv.), base (0.6 mmol, 2 equiv.),
and additive (3 mol %) in distilled H2O (2 mL) was stirred at 80 oC for 18 h under
b
air. Yields were determined by GC using n−hexadecane as the internal
standard. Mo(CO)6 (0.09 mmol, 0.3 equiv.). Mo(CO)6 (0.15 mmol, 0.5 equiv.).
c
d
e
Mo(CO)6 (0.24 mmol, 0.8 equiv.).
Our initial investigation was started with anthranil (1a, 1
equiv.), iodobenzene (2a, 2.5 equiv.), Pd/C (10 mol %),
[Mo(CO)6] (1 equiv.), and Cs2CO3 (2 equiv.) in distilled water. To
our delight, 16% yield of the desired carbonylation product 3a
was formed after 18 hours at 80 oC (Table 1, entry 1).
Subsequently, various bases were tested (Table 1, entries 2-5).
Et3N (triethylamine) was found to be the best in this reaction,
whereas DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), DABCO
(1,4−diazabicyclo[2.2.2]octane), and DiPEA (N,N-diisopropyl-
ethylamine) were all found to be inferior. To further improve the
[a]
Z. Wang, Z. Yin, Prof. Dr. X.-F. Wu, Leibniz-Institut für Katalyse e.V.
an der Universität Rostock, Albert-Einstein-Straße 29a, 18059
Rostock, Germany; Prof. Dr. X.-F. Wu, Department of Chemistry,
Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018,
People's Republic of China
E-mail: xiao-feng.wu@catalysis.de
Supporting information for this article is given via a link at the end of
the document.
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10.1002/chem.201703994
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%), Mo(CO)6 (0.15 mmol, 0.5 equiv.), Et3N (0.9 mmol, 3 equiv.), TBAB (0.009 mmol, 3
mol %), H2O (2 mL), 80 oC, 18 h, air, isolated yield.
outcome, different additives were used in this reaction (Table 1,
entries 6-8). Surprisingly, we found that the desired product 3a
can be formed in 62% yield with TBAB (tetrabutylammonium
bromide) as the additive (Table 1, entry 6). Replacement of
TBAB with TBAC (tetrabutylammonium chloride) or TBAHS
(tetrabutylammonium hydrogen sulfate) proved detrimental to
the efficiency of the process, with product 3a being formed in
56% and 49% yields, respectively (Table 1, entries 7-8). Next we
increased the amount of TBAB to 5 mol % and 10 mol % in the
reaction conditions (Table 1, entries 9-10). However, the yield of
product 3a decreased. Different loadings of the Et3N affected the
reaction yields, and we obtained 73% yield of product 3a with 3
equivalents of Et3N (Table 1, entries 11-12). Notably, the amount
of Mo(CO)6 played a crucial role for the outcome of this reaction
(Table 1, entries 13-15). The yield of the desired product can be
improved to 83% by adding 0.5 equivalent of Mo(CO)6 (Table 1,
entry 14). Additionally, the yield decreased with 1.5 equivalent of
iodobenzene and only 32% of the desired product could be
detected with one equivalent of iodobenzene. The same yield
can be obtained if perform the reaction under argon, and proves
this system tolerable with aerobic conditions.
With the optimized conditions in hand (Table 1, entry 14), a
series of aryl iodides were tested subsequently. As shown in
Scheme 1, various aryl iodides with either electron-donating or
electron-withdrawing groups worked well under our reaction
conditions and gave the corresponding amides in moderate to
good yields. Substrates can tolerate various functional groups
such as CH3, Bn, OCH3, CF3, Br, Cl, F, and COOMe. However,
aryl iodides substituted with OH, NH2 or NO2 could not give the
desired carbonylation products. The system permitted the
reaction of sterically hindered aryl iodides such as 2−iodotoluene,
2−iodoanisole, 1-chloro-2-iodobenzene and 2-bromoiodo-
benzene with anthranils providing 70%, 75%, 68%, and 63%
yield, respectively (3c, 3g, 3l, 3m). The reaction of the
heterocyclic iodide 3-iodopyridine with anthranil proceeded
smoothly under these reaction conditions and providing 75%
yield of the desired product 3o. Interestingly, methyl 4-
iodobenzoate reacted with anthranil and provided the highest
yield of the corresponding product 3p in 88%.
Scheme 2. Amides synthesis; variation of anthranils. Reaction conditions: Anthranils 1
(0.3 mmol, 1 equiv.), aryl iodides 2 (0.75 mmol, 2.5 equiv.), Pd/C (3.2 mg, 10 mol %),
Mo(CO)6 (0.15 mmol, 0.5 equiv.), Et3N (0.9 mmol, 3 equiv.), TBAB (0.009 mmol, 3 mol
%), H2O (2 mL), 80 oC, 18 h, air, isolated yield.
Then, various anthranils were investigated for further
extending the substrates scope (Scheme 2). Several substituted
anthranils performed well and delivered the corresponding
amides in moderate to good yields. Owing to the mild reaction
conditions, different functional groups, such as F, Cl, CF3, and
NMe2, can be contained in the substrates. In addition,
introduction of a substituted methyl group into the 3−position of
Scheme 1. Amides synthesis; variation of aryl iodides. Reaction conditions: Anthranil
1a (0.3 mmol, 1 equiv.), aryl iodides 2 (0.75 mmol, 2.5 equiv.), Pd/C (3.2 mg, 10 mol
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10.1002/chem.201703994
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the anthranil ring was fully tolerated, giving the desired amides
in 85% and 86% yields (4a and 4f). Additionally, as one
advantages of heterogeneous catalyst, catalyst recycle
experiments were performed as well. In our model system, the
catalyst can be reused for several times (see SI), and 54 % yield
can still be achieved at the third run. 4-Bromoisoxazole was
tested with iodobenzene as well, but no desired product could
be detected.
We could only get 3a in 80% yield, and no deuterated product
was detected which might due to the instability of N-D bond.
Notably, PhOTf can be applied as the substrate as will and
provide the desired product in 65% yield without any further
optimization (Scheme 3, g). And 2-aminobenzaldehyde was
tested as well and gives 83% of the corresponding product
under our standard conditions (Scheme 3, h).
Scheme 4. Proposed mechanism.
According to the control experiments, we postulated a
possible reaction mechanism for this palladium-catalysed
aminocarbonylation (Scheme 4). Firstly, the iodobenzene
reacted with palladium to give the aryl palladium complex A.
Then carbon monoxide, which was produced from Mo(CO)6,
coordinated and inserted into palladium complex A to generate
the acyl palladium complex B. This acyl palladium complex B
reacted with 2−aminobenzaldehyde to give the final product and
regenerated the palladium catalyst for the next catalytic cycle.
In conclusion, we have developed a convenient procedure
for the synthesis of N-(2-carbonylaryl)benzamides. Moderate to
good yields of the desired amides can be prepared with good
functional group tolerance. Additionally, this procedure also have
advantages such as recyclable Pd/C catalyst, safe Mo(CO)6 as
the solid CO source, water as environmentally benign solvent,
and no inert gas protection.
Scheme 3. Control experiments, isolated yield.
Experimental Section
To understand the mechanism, some control experiments
were performed. From the Scheme 3a and 3b, we found that the
cleavage of N−O bond would take place in the presence of Pd/C
and the presence of Mo(CO)6 improves the yield (Scheme 3, c).
In the absence of Mo(CO)6, no direct crosscoupling product 2-
(phenylamino)benzaldehyde could be detected but only
2−aminobenzaldehyde was formed in 30% yield (Scheme 3, d).
These results shown the importance of Pd/C and the dual roles
of Mo(CO)6 (promote the generation of 2−aminobenzaldehyde
and CO source). We can get N−phenylbenzamide in 76% yield
when aniline instead of anthranil under our standard conditions
(Scheme 3, e). Then D2O was used as the solvent in Scheme 3f.
General procedure: In a 25 mL sealed tube, a mixture of anthranils 1 (0.3
mmol, 1 equiv.), aryl iodides 2 (0.75 mmol, 2.5 equiv.), Pd/C (3.2 mg, 10
mol %), Mo(CO)6 (0.15 mmol, 0.5 equiv.), Et3N (0.9 mmol, 3 equiv.), and
TBAB (0.009 mmol, 3 mol %) in distilled water (2 mL) was stirred at 80 oC
under air. After 18 h, the mixture was cooled to room temperature. The
residue was diluted with H2O solution (10 mL) and extracted with EtOAc
(3×10 mL). The solvent was then evaporated under vacuum. The crude
products were purified by using column chromatography on silica gel
(pentane/ethyl acetate) to give the pure products.
Acknowledgements
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Zechao Wang, Zhiping Yin, and Xiao-
Feng Wu*
Page No. – Page No.
Pd/C-Catalysed Aminocarbonylation
of Aryl Iodides with Anthranils in
Water Using Mo(CO)6 as the CO
Source
A convenient procedure for the synthesis of N-(2-carbonylaryl)benzamides has
been developed. Through Pd/C−catalysed aminocarbonylation of anthranils with
various hindered and functionalized aryl iodides, the desired amides were afforded
in moderate to good yields. The protocol is advantageous due to the recyclable
Pd/C catalyst, safe Mo(CO)6 as the solid CO source, and environmentally benign
water as solvent.
This article is protected by copyright. All rights reserved.