A Convenient Palladium-Catalyzed Aminocarbonylation of Aryl Iodides to Primary Amides under Gas-Free Conditions

Article abstract of DOI:10.1002/ejoc.201701105

A convenient procedure for the synthesis of aromatic primary amides through palladium-catalyzed aminocarbonylation of aryl iodides has been developed. With ammonium hydrogen carbonate as the solid nitrogen source and formic acid as the liquid CO source, a variety of primary amides were obtained in moderate to excellent yields under gas-free conditions.

Full text of DOI:10.1002/ejoc.201701105

A Journal of
Accepted Article
Title: A Convenient Palladium-Catalyzed Aminocarbonylation of Aryl
Iodides to Primary Amides under Gas-free Conditions
Authors: Xiao-Feng Wu, Xinxin qi, Han-Jun ai, Chuang-Xu cai, Jin-Bao
peng, and Jun ying
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701105
Link to VoR: http://dx.doi.org/10.1002/ejoc.201701105
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10.1002/ejoc.201701105
European Journal of Organic Chemistry
COMMUNICATION
A Convenient Palladium-Catalyzed Aminocarbonylation of Aryl
Iodides to Primary Amides under Gas-free Conditions
Xinxin Qi,[a] Han-Jun Ai,[a] Chuang-Xu Cai,[a] Jin-Bao Peng,[a] Jun Ying,[a] and Xiao-Feng Wu*[a,b]
Abstract: A convenient procedure for the synthesis of aromatic
primary amides via palladium-catalyzed aminocarbonylation of aryl
iodides has been developed. With ammonium bicarbonate as the
solid nitrogen source and formic acid as the liquid CO source, a
variety of primary amides were obtained in moderate to excellent
yields under gas-free conditions.
Hence a new procedure without gas manipulation will be
attractive and under current demanding. In this communication,
we wish to report a newly developed palladium-catalyzed
aminocarbonylation procedure for the synthesis of primary
amides. With ammonium bicarbonate as the solid nitrogen
source and formic acid as the liquid CO source, a variety of
primary amides were obtained in moderate to excellent yields.
Notably, no gas manipulation is needed here.
Primary aromatic amides are valuable synthetic intermediates in
organic chemistry and have been used as starting materials for
producing engineering plastics, detergents, and lubricants.[1]
Due to the obvious importance, various procedures have been
developed for their preparation. For example, primary
benzamides can be synthesized by 1) hydration of the
corresponding aromatic nitrile,[2] 2) conversion of benzoic acids
or acid chlorides with ammonia,[3] 3) transformation of
benzaldehydes or benzaldoximes,[4] and 4) oxidation of primary
benzyl amines or alcohols.[5] Despite those well established
methods, there is continuing interest in the development of new
or improved methodologies for their synthesis.
On the other hand, since the first report on palladium-
catalyzed carbonylation of aryl halides by Heck and co-workers
in 1974,[6] palladium-catalyzed carbonylative reactions have
drawn increasing attention both in academic and industrial fields.
Currently, this strategy plays an important role in organic
synthesis and has emerged as a powerful tool in the synthesis of
a wide range of carbonyl-containing compounds, such as
aldehydes, ketones, carboxylic acids and their derivatives.[7] Not
surprisingly, carbonylation methodologies for primary amides
synthesis have been developed as well. In general, in the
presence of carbon monoxide, various ammonia surrogates
were explored, such as hexamethyldisilazane (HMDS),[8]
formamide,[9] N-tert-butylamides,[10] hydroxylamine,[11] titanium–
nitrogen complex,[12] and ammonium salts.[13]. Interestingly,
Beller and co-workers reported the directly usage of ammonia
gas as the ammonia source and base recently.[14] Good yields of
primary amides can be produced from aryl halides and aryl
nonaflates in good yields. However, most of these reactions
were carried out under pressure of CO gas. Due to the
properties of CO such as high toxicity and odorless, lead CO
gas related methodologies are less applied in laboratories.
Initially, iodobenzene and ammonium bicarbonate were
chosen as model substrates, using Pd(OAc)2 as catalyst with
PPh3 as ligand in CH3CN at 100 °C for 24 h. To our delight, 54%
yield of the desired benzamide was obtained (Table 1, entry 1).
It was noteworthy that the reaction time has dramatic effects on
the yield of benzamide (Table 1, entries 2-4), and 92% yield was
observed after 10 hours (Table 1, entry 3). Then we investigated
the efficiency of different ligands, both bidentate and
monodentate ligands examined provided the target product in
lower yields (Table 1, entries 5-9). Subsequently, some other
palladium pre-catalysts including PdCl2(PPh3)4, Pd2(dba)3, and
Pd(PPh3)4 were studied, resulting the corresponding benzamide
in very low yields (Table 1, entries 10-12). Some other organic
solvents were tested as well, and acetonitrile proven to be the
optimal solvent (Table 1, entry 13-15).
Table 1. Optimization of the reaction conditions.[a]
Entry
1
Catalyst
Ligand
PPh3
Solvent
T (h)
24
16
10
8
Yield(%)[b]
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(PPh3)4
Pd2(dba)3
Pd(PPh3)4
Pd(OAc)2
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
toluene
54
76
92
42
83
49
46
38
53
20
26
trace
6
2
PPh3
3
PPh3
4
PPh3
5
dppf
10
10
10
10
10
10
10
10
10
6
Xantphos
PCy3
7
[a]
[b]
Dr. X. Qi, H.-J. Ai, C.-X. Cai, Dr. J.-B. Peng, Dr. J. Ying, 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
8
P(o-tol)3
P(p-anis)3
PPh3
9
10
11
12
13
Prof. Dr. X.-F. Wu
Leibniz-Institut für Katalyse e.V. an der Universit Rostock, Albert-
Einstein-Strasse 29a, 18059 Rostock, Germany
https://www.catalysis.de/mitarbeiter/wu-xiao-feng/
PPh3
PPh3
Supporting information for this article is given via a link at the end of
the document.
PPh3
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10.1002/ejoc.201701105
European Journal of Organic Chemistry
COMMUNICATION
14
15
Pd(OAc)2
Pd(OAc)2
PPh3
PPh3
1,4-dioxane
DMSO
10
10
30
0
4
5
93%
95%
aReaction conditions: iodobenzene (0.5 mmol), ammonium bicarbonate (3.5
mmol), catalyst (5 mol%), ligand (10 mol% for monodentate ligand; 5 mol% for
bidentate ligand), formic acid (2.0 mmol), DCC (2.0 mmol), solvent (3.5 mL),
100 oC. bGC yield, with dodecane as the internal standard. DCC
dicyclohexylcarbodiimide.
=
With the best reaction conditions in hand, we began to
study the substrate scope of this transformation with a variety of
aryl iodides (Table 2). Aryl iodides with electron-donating group,
involving methyl, ethyl, t-butyl, and methoxy at ortho-, meta-,
and para- position provided the corresponding primary amide
products in good to excellent yields (Table 2, entries 2-9).
Substrates with electron-deficient groups such as ester, cyano,
acetyl, nitro, and trifluoromethyl groups can be transformed and
gave the desired products in moderate to excellent yields as well
(Table 2, entries 10-14). Here, it’s important to mention that nitro
group is not tolerable under pressure of carbon monoxide due to
its reducibility. In addition, substrates with fluoro, chloro, and
bromo substitution can be applied as well, the desired products
were obtained in good yields (Table 2, entries 15-18). And the
obtained products are ready for further modifications via cross-
coupling reactions. Furthermore, the substrates with 1-naphthyl
and 2-naphthyl moieties can also smoothly participate in the
reaction to give the corresponding products in 90% and 70%
yields, respectively (Table 2, entries 19 and 20). Additionally,
heteroaryl iodides can be applied under the reaction too, the
desired primary amide products were isolated in 58% and 85%
yields (Table 2, entries 21 and 22). Concerning the roles of the
reagents, formic acid is been dehygenerated by DCC
(dicyclohexylcarbodiimide) to release CO in situ. Ammonium
bicarbonate has been used as ammonia source and base as
here.
6
90%
7
8
90%
92%
9
89%
51%
10
11
12
13
55%
Table 2. Primary amides synthesis under gas-free conditions.[a]
48%[b]
45%[b]
Entry
1
Product
Yield
90%
14
15
16
95%
2
3
93%
80%
65%[b]
65%[b]
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10.1002/ejoc.201701105
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aReaction conditions: aryl iodides (0.5 mmol), ammonium bicarbonate (3.5
mmol), Pd(OAc)2 (5 mol%), PPh3 (10 mol%), formic acid (2.0 mmol), DCC (2.0
mmol), acetonitrile (3.5 mL), 100 oC, 10-12 h, isolated yields. b90 oC.
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In summary, we have developed a convenient palladium-
catalyzed aminocarbonylation of aryl iodides for the synthesis of
primary amides. With ammonium bicarbonate as ammonia
source and base, with formic acid as the CO precursor, a wide
range of aryl iodides were transformed into the corresponding
aromatic primary amides in moderate to excellent yields.
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Experimental Section
Pd(OAc)2 (5 mmol%), PPh3 (10 mmol%), NH4HCO3 (3.5 mmol), and DCC
(2.0 mmol) were transferred into an oven-dried tube, which was
evacuated and backfilled with N2 (5x). Acetonitrile (3.5 mL), aryl iodide
(0.5 mmol), and HCOOH (2.0 mmol) were added into the tube via syringe.
The reaction mixture was stirred at 100 °C for 10-12 h. After the reaction
was complete, the mixture was filtrated, concentrated and purified by
flash column chromatography on silica gel (DCM/MeOH) to afford the
pure product
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Keywords: palladium catalyst • carbonylation • aryl iodides •
primary amides • gas-free
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COMMUNICATION
COMMUNICATION
Xinxin Qi, Han-Jun Ai, Chuang-Xu Cai,
Jin-Bao Peng, Jun Ying, and Xiao-Feng
Wu*
Page No. – Page No.
A Convenient Palladium-Catalyzed
Aminocarbonylation of Aryl Iodides
to Primary Amides under Gas-free
Conditions
NO GAS! An efficient synthesis of aromatic primary amides via palladium-catalyzed
aminocarbonylation of aryl iodides has been developed. With ammonium
bicarbonate as the solid nitrogen source and formic acid as the liquid CO source, a
variety of primary amides were obtained in moderate to excellent yields under gas-
free conditions
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