Polyethylene glycol as a recyclable reaction medium for gold-catalysed direct oxidative amide synthesis from aldehydes and amines

Article abstract of DOI:10.3184/174751915X14449273097235

Polyethylene glycol (PEG) was used as the recyclable reaction medium for gold-catalysed oxidative amidation of aldehydes with amines by using tert-butyl hydroperoxide (TBHP, 70% aqueous) as the oxidant. The reaction proceeded efficiently to provide the corresponding products in moderate to good yields under mild conditions. Both the catalysts and solvent can be easily recovered and reused by simple extraction without significant loss of activity.

Full text of DOI:10.3184/174751915X14449273097235

654 RESEARCH PAPER
VOL. 39 NOVEMBER, 654–656
JOURNAL OF CHEMICAL RESEARCH 2015
Polyethylene glycol as a recyclable reaction medium for gold-catalysed direct
oxidative amide synthesis from aldehydes and amines
Hui-liang Jiang* and Jie Zhao
School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, Jiangsu Province, P. R. China
Polyethylene glycol (PEG) was used as the recyclable reaction medium for gold-catalysed oxidative amidation of aldehydes with amines
by using tert-butyl hydroperoxide (TBHP, 70% aqueous) as the oxidant. The reaction proceeded efficiently to provide the corresponding
products in moderate to good yields under mild conditions. Both the catalysts and solvent can be easily recovered and reused by simple
extraction without significant loss of activity.
Keywords: gold catalysis, oxidative amidation, polyethylene glycol medium, recycling
Amides are ubiquitous and very important structural motifs
present in a wide range of materials and in pharmaceuticals and
22,23
On the other hand, Barbas et al.
developed the oxidative
amidation of alcohols with amines and azides using gold
as catalyst (Scheme 1d). Although these methods afforded
satisfactory results, recovery and reuse of the catalysts could not
be achieved. Thus, the high cost of both catalysts and ligands as
well as organic solvents limited their practical use in industry.
In recent years, PEG (polyethylene glycol) has been applied as
a novel solvent for organic reactions due to its non-toxicity and
its cheap, stable and environmentally friendly properties.
More importantly, PEG can be used for catalyst recycling in
a broad range of organic reactions including polymerisation
1-4
biologically active compounds. Traditional approaches for the
synthesis of amides mainly involve amidation reactions between
carboxylic acids or activated carboxylic acid derivatives such as
5,6
acid anhydrides and acid halides with amines. However, the
toxicity of the reagents and the harsh reaction conditions are
major drawbacks that still need to be addressed.
2
4-27
Recently, direct amidation of alcohols or aldehydes with
amines has attracted considerable attention due to the high
7
-17
atom economy and easy availability of substrates.
In 2006,
18
28-33
the Li group reported a CuI/AgIO /T-HYDRO mediated
and biotransformation.
We now report a Ph PAuCl/TBHP
3
3
oxidative coupling reaction between aldehydes and amine
mediated oxidative coupling reaction between aldehydes and
amines in PEG-400 (Scheme 1e). The catalysts immobilised
in PEG-400 medium can be easily recycled without significant
loss of activity.
19
hydrochlorides (Scheme 1a). The Leow group and the Wong
2
0
group disclosed a photo-induced aerobic oxidative amidation
of aromatic aldehydes with amines by using phenazinium
salt and rose bengal as the catalyst, respectively (Scheme 1b).
21
Results and discussion
Recently, Wang et al. developed a catalyst-free amidation
of aldehydes with amines in aqueous media by employing
trichloroisocyanuric acid (TCCA) as additive (Scheme 1c).
Initially, benzaldehyde 1a and aniline 2a were employed as the
starting materials to optimise the reaction conditions. A variety
Previous Work
O
O
CuI, AgIO3
base heat
alkyl
H
H
+
+
alkyl NH2 HCl
N
H
(
a)
b)
R
R
O
O
R1
R2 photocatalyst
R2
N
H
(
N
R1
R1
visible-light, air
R1
O
TCCA
O
+
2
3
(
c)
d)
R R NH
R1
H
R1
2
3
H O
NR R
2
O
H N
2
OH
Au/DNA
+
or
N
H
(
R
R
O , base
2
N3
This Work
R2
O
O
R2
Ph PAuCl, TBHP
3
H + H N
N
H
(
e) R1
2
R1
PEG 400
Scheme 1 Different pathways for oxidative amidation.
*
Correspondent. E-mail: jiangnanhg@163.com

JOURNAL OF CHEMICAL RESEARCH 2015 655
a
a
Table 1 Optimisation of reaction conditions
Table 2 Reaction scope for aldehyes and amines
O
O
O
O
Ph PAuCl, TBHP
3
Catalyst, Oxidant
solvent
+
H N R2
2
R2
H + H N
N
H
R1
R1
2
H
N
PEG-400
H
1
2
3
1a
2a
3a
1
2
b
lit.
Entry R
R
Product Yield/% M.p./°C
b
Entry Catalyst
Oxidant
Solvent
Yield/%
32
NR
2
2
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
78
82
66
75
83
72
80
56
61
51
78
86
75
53
77
68
46
160–162 (162–163)
1
2
3
4
5
6
7
8
9
Pd(OAc)2
TBHP
TBHP
TBHP
TBHP
TBHP
K S O
CH CN
3
22
4-ClC6H4
2-ClC6H4
4-BrC6H4
4-MeC6H4 Ph
4-OMeC6H4 Ph
4-NO C H Ph
2-furyl
1-naphthyl Ph
1-butyl
Ph
Ph
200–204 (200–201)
c
AgOTf
Cu(OAc)2
CH CN
3
22
113–114 (114–115)
CH CN
NR
18
66
NR
NR
NR
33
26
78
45
51
58
28
3
22
198–200 (202–204)
146–147 (143–144)
170–173 (173–174)
214–216 (215–216)
CuI
CH CN
3
22
Ph PAuCl
CH CN
3
3
22
Ph PAuCl
CH CN
3
2
2
8
3
22
2
6 4
Ph PAuCl
PhI(OAc)2
CH CN
3
3
22
Ph
124–125 (126–127)
Ph PAuCl
O2
CH CN
3
3
22
165–167 (164–165)
Ph PAuCl
DDQ
CH CN
3
3
22
1
0
Ph
4-ClC6H4
4-MeC6H4 3l
4-OMeC6H4 3m
4-NO C H 3n
piperidine 3o
benzyl
1-butyl
3j
3k
60–61 (59–61)
10
Ph PAuCl
H2O
CH CN
3
2
3
22
1
1
202–204 (199–200)
11
Ph PAuCl
TBHP
PEG400
DMF
THF
3
22
1
2
155–156 (157–158)
160–162 (161–162)
198–200 (197–198)
12
Ph PAuCl
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
3
22
1
3
Ph
Ph
Ph
Ph
13
Ph PAuCl
3
22
1
4
2
6 4
14
Ph PAuCl
MeOH
3
23
1
5
80–82 (82–84)
15
Ph PAuCl
1,4-dioxane
PEG-400
PEG-400
PEG-400
PEG-400
3
22
1
6
3p
3q
104–106 (104–105)
d
e
h
16
Ph PAuCl
63 , 74
3
22
17
Ph
Yellow oil
f
17
Ph PAuCl
78
3
a
Reaction conditions: 1 (1 mmol), 2 (1 mmol), Ph PAuCl (2 mol%), TBHP (1.1 equiv.),
g
3
18
Ph PAuCl
72 , 57
o
3
PEG-400 (1 mL), 50 C.
Isolated yield.
i
j
19
Ph PAuCl
Trace , 68
b
3
a
Reaction conditions: 1a (1 mmol), 2a (1 mmol), catalyst (2 mol%), oxidant (1.1 equiv.),
o
solvent (1 mL), 50 C.
b
Isolated yield.
No reaction.
c
d
1
4
mol% of catalyst.
mol% of catalyst.
.0 equiv. of oxidant.
e
f
2
g
2
0
mL of solvent.
.5 mL of solvent.
h
i
Room temperature.
J
o
8
0 C.
of reaction conditions including catalyst, oxidant, solvent as
well as temperature were explored (Table 1). Results showed
that, the reaction proceeded smoothly in the presence of 2 mol%
of Ph PAuCl and 1.1 equiv. of TBHP in PEG-400 at 50 °C for
3
8
h. The desired product 3a was furnished in 78% yield (Table
Fig.
1 Recycling experiment (Reaction conditions: 1 (1 mmol),
o
1, entry 11). Catalysts such as Pd(OAc) , AgOTf, Cu(OAc)
2
2
2 (1 mmol), Ph PAuCl (2 mol%), TBHP (1.1 equiv.), PEG-400 (1 mL), 50 C.)
3
and CuI resulted in either the failure of the reaction or much
lower yields (Table 1, entries 1–4). The oxidants also showed an
important influence on this transformation. No desired product
was observed when K S O , PhI(OAc) and O were used (Table
donating groups gave satisfactory results (Table 2, entries 2–7).
Other aromatic or heterocyclic aldehydes, such as 2-furaldehyde
and1-naphthaldehyde, were found to be compatible with this
system affording products 3h and 3i in moderate yields (Table
2, entries 8 and 9). For alkyl aldehydes such as propionaldehyde,
relatively lower yields were obtained (Table 2, entry 10). The
steric hindrance also had some influence on the reaction. For
example, 4-chloroaniline provided the product 3b in 82%, and
3c was obtained in 66% yield when 2-chloroaniline was used
(Table 2, entries 2 and 3). Moreover, the electronic properties of
the substituent on aromatic amines had a significant influence
on this reaction. Amines bearing electron-withdrawing groups
such as nitro gave the desired products in relatively lower yields
(Table 2, entry 14). Both heterocyclic and alkyl amines were
found to be compatible with the reaction conditions to afford
the desired products in 77–46% yields (Table 2, entries 15–17).
Having established the efficiency of this catalytic system, the
recovery and reuse of the catalysts were then studied. When the
2
2
8
2
2
1, entries 6–8). A reaction using DDQ and H O gave rather
2 2
low yields of product (Table 1, entries 9 and 10). Compared
with CH CN, DMF, THF, MeOH and 1,4-dioxane, the use of
PEG-400 as solvent resulted in higher yields (Table 1, entries
3
1
1–15). Further optimisation showed that no higher yield was
obtained when the amount of catalyst or oxidant was increased
Table 1, entries 16 and 17). Reaction concentration was further
(
-1
evaluated. The result clearly showed that 1 mol L of aldehyde
was the optimum (Table 1, entry 18). Finally, the survey on
the reaction temperature showed that 50 °C was the optimum
(
Table 1, entry 19).
With these optimised conditions in hand, the scope of the
reaction was explored (Table 2). Generally, all of the investigated
aldehydes coupled with amines smoothly to provide the desired
products in moderate to good yields (44–86%). For substituted
aromatic aldehydes, both electron-withdrawing and electron-

656 JOURNAL OF CHEMICAL RESEARCH 2015
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1
4
5
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Experimental
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0
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2
2
A suspension of the amine (1 mmol), aldehyde (1 mmol), TBHP (1.1
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Received 19 August 2015; accepted 3 October 2015
Paper 1503553 doi: 10.3184/174751915X14449273097235
Published online: 1 November 2015
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