One-pot microwave-assisted tandem deprotection of arylmethanesulfonates / SNAr reaction for K2CO3-mediated C(aryl)-O bond formation

Article abstract of DOI:10.1515/znb-2007-0912

One-pot microwave-assisted tandem deprotection of arylmethanesulfonates / nucleophilic aromatic substitution reaction (S_NAr) with activated aryl halides to synthesize asymmetrical diaryl ethers is described.

Full text of DOI:10.1515/znb-2007-0912

One-pot Microwave-assisted Tandem Deprotection of
Arylmethanesulfonates / S Ar Reaction for K CO -mediated
N
2
3
C(Aryl)–O Bond Formation
Hui Xu and Hong-Feng Li
College of Science, Northwest A & F University, Yangling 712100, Shaanxi Province, China
Reprint requests to Prof. Dr. Hui Xu. Fax: +86(0)29/87092226. E-mail: orgxuhui@nwsuaf.edu.cn
Z. Naturforsch. 2007, 62b, 1183 – 1186; received January 24, 2007
One-pot microwave-assisted tandem deprotection of arylmethanesulfonates / nucleophilic aro-
matic substitution reaction (S Ar) with activated aryl halides to synthesize asymmetrical diaryl ethers
N
is described.
Key words: Tandem Reaction, Arylmethanesulfonates, S Ar, Aryl Halides, Cross-coupling
N
Introduction
remarkable decrease in reaction times, increased
yields, and easier workup, consistent with green chem-
istry protocols, has become a very popular and useful
technology in synthetic organic chemistry [7 – 8].
As part of the development of environmentally be-
nign new methodologies [9 – 10], herein we wish to re-
As biaryl ethers are very important intermediates
in natural products chemistry as well as in numerous
biologically active compounds such as vancomycin
and riccardin, carbon(aryl)-oxygen bond formation is
a powerful and important tool of modern organic syn-
thesis [1]. The classical Ullmann-type ether synthesis
port our studies on the microwave-assisted S Ar-type
N
direct C–O bond formation from activated aryl halides
and various aryl methanesulfonates in the presence of
K CO at an irradiation power of 230 W (Fig. 1).
◦
often requires high temperature (200– 300 C), long
reaction times (24 h), and strongly polar and toxic
solvents [2]. Recently, considerable efforts have been
made to develop valuable methodologies for the for-
mation of diaryl ethers [3 – 5]. The methanesulfonyl
group is a useful and potent protecting group for a phe-
2
3
Results and Discussion
Initially we investigated the microwave-assisted
nol, and therefore it is interesting that the methanesul- coupling of 4-fluoronitrobenzene (1.0 mmol) with 4-
fonyl protecting group for a phenol is unmasked un- chlorophenyl methanesulfonate in DMSO (10 mL) at
der the conditions of the S Ar reaction with an aryl an irradiation power of 230 W for optimization of the
N
halide, producing diaryl ether directly [6]. Although reaction conditions, and the results are summarized in
Dinsmore reported the synthesis of diaryl ethers from Table 1. The best yield was obtained when K2CO3was
arylmethanesulfonates and 2-fluoronitrobenzene, this used as the base at a reaction time of 10 min and ap-
method required the use of expensive Cs CO in ex- plying 2.5 equiv. of 4-chlorophenyl methanesulfonate.
2
3
cess and very long reaction times (6 – 48 h) and had a
Based on the above finding, we further studied the
narrow application scope of substrates [6]. Microwave coupling reaction of different aryl methanesulfonates
irradiation as an alternative energy source leading to a with activated aryl halides in the presence of K2CO3
Fig. 1. Microwave-assisted tan-
dem deprotection of arylmethane-
sulfonates / S Ar reaction to
N
synthesize unsymmetrical diaryl
ethers.
0932–0776 / 07 / 0900–1183 $ 06.00 © 2007 Verlag der Zeitschrift f u¨ r Naturforschung, T u¨ bingen · http://znaturforsch.com
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1184
H. Xu – H.-F. Li · Arylmethanesulfonates / S Ar Reaction for K CO -mediated C(Aryl)–O Bond Formation
N
2
3
Table 1. Optimization of microwave-assisted synthesis of 4-
reaction times are very short (10 – 12 min) and moder-
ate to good yields (39– 75%) were achieved without
any catalyst for a wide substrate range including aryls
with electron-deficient substituents. Moreover, K CO
ꢀ
(
4 -chlorophenoxy)nitrobenzene.
2
3
is a cheaper base as compared to the previously used
Cs CO [6].
2
3
Experimental Section
Entry Base
Amount of
Time Yield
base (mmol) A (mmol) B (mmol) (min) (%)
The materials were used as purchased, and DMSO was
used directly without any additional purification. Melting
points are uncorrected. H NMR spectra were recorded on a
Bruker Avance DMX 400 instrument using TMS as internal
standard and CDCl3 as solvent. HR and EI mass spectra were
obtained with APEX II Bruker 4.7T AS and Thermo DSQ
GC/MS instruments, respectively. Microwave irradiation was
performed in a Haier microwave oven, MO-2270M1.
1
2
3
4
5
6
7
8
9
0
1
2
3
K2CO3
NaHCO3
CaO
2
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2.0
2.5
3.0
2.5
2.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
8
8
8
8
8
10
11
12
10
10
10
10
10
45
4
10
5
30
65
65
51
69
75
79
64
73
2
2
2
2
2
2
2
2
2
2
1.5
2.5
1
CaCl2
NaOH
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
1
1
1
1
General procedure
To a mixture of an activated aryl halide (X = F, Cl, Br,
1
mmol), an aryl methanesulfonate (2.5 mmol) and K CO
2 3
under microwave irradiation. From the results shown (2 mmol) was added DMSO (10 – 25 mL). The reaction was
found not to be sensitive to air and moisture, hence DMSO
was used directly without any additional purification, and
there was no need for inert-atmosphere techniques. The mix-
ture was placed in a microwave oven and irradiated at a
power of 230 W for 10 – 12 min. The progress of the reaction
was monitored by thin-layer chromatography (TLC). After
completion of the reaction, the mixture was cooled to r. t.,
poured into ice water (40 mL) and stirred for 5 min. Then
in Table 2 it can be seen that a range of aryl
methanesulfonates, including those with electron-de-
ficient and electron-rich substitutents, were effective
for this C–O cross-coupling S Ar reaction even with
N
electron-deficient aryl halides (X = F, Cl, Br) such as
2
-fluoronitrobenzene, 4-fluoronitrobenzene, 2-fluoro-
benzonitrile, 2-chloronitrobenzene and 4-bromonitro-
benzene in the presence of 2 equivalents of K CO
2
3
6
0 mL of EtOAc was added, the organic layer was sepa-
rated and the aqueous layer was extracted with EtOAc (2 ×
0 mL). The combined organic extracts were washed with
as the base under microwave irradiation in DMSO
medium (Table 2, entries 2 – 9). Moderate to good
yields (39 – 75 %) were obtained in 10– 12 min with-
out any catalyst.
It should be recalled at this point that aryl methane-
sulfonates with electron-deficient substituents behave
poorly or are completely inert toward diaryl ether for-
6
brine (40 mL) and dried over anhydrous MgSO . After re-
4
moval of the solvent under reduced pressure, the residue was
purified by preparative thin-layer chromatography (PTLC) to
give the pure diaryl ether.
ꢀ
mation. According to entry 6, even the reaction with 2-(3 -Methylphenoxy)nitrobenzene (1)
the extremely electron-poor 4-nitrophenyl methane-
sulfonate afforded 2-(4 -nitrophenoxy)-nitrobenzene
in 39 % yield.
1
Pale yellow liquid. – H NMR (400 MHz, CDCl ): δ =
ꢀ
3
2
7
.34 (3H, s), 6.83 (2H, m), 6.99 (2H, m), 7.15 (1H, t, J =
.6 Hz), 7.23 (1H, t, J = 8.0 Hz), 7.46 (1H, dt, J = 8.0 Hz,
J = 1.6 Hz), 7.93 (1H, dd, J = 7.6 Hz, J = 1.6 Hz). – HRMS-
FAB: m/z = 247.1080 (calcd. 247.1077 for C H NO ,
Conclusion
13
11
3
+
[
M+NH ] ).
4
In conclusion, we have introduced an efficient one-
pot tandem-type reaction to synthesize unsymmetri-
cal diaryl ethers via consecutive deprotection of aryl
methanesulfonates (including those with electron-defi-
ꢀ
2
-(4 -Chlorophenoxy)nitrobenzene (2)
1
Pale yellow liquid. – H NMR (400 MHz, CDCl ): δ =
3
cient substituents) and C–O bond cross-coupling in the 6.96 (3H, m), 7.21 (1H, t, J = 8.0 Hz), 7.31 (2H, m), 7.51
presence of K CO under microwave irradiation. The (1H, dt, J = 8.4 Hz, J = 1.6 Hz), 7.95 (1H, dd, J = 8.4 Hz,
2
3
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H. Xu – H.-F. Li · Arylmethanesulfonates / S Ar Reaction for K CO -mediated C(Aryl)–O Bond Formation
1185
N
2
3
Table 2. Microwave-assisted syn-
thesis of unsymmetrical diaryl
ethers.
Entry
I
III
IV
Time Yield
min) (%)
(
1
2
3
4
5
6
12
12
10
10
10
12
50
50
63
53
50
39
7
12
61
8
9
12
10
51
75
J = 1.6 Hz). – GC/MS (EI, 70 eV): m/z (%) = 251 (10.8), 249 1.6 Hz), 8.19 (2H, m). – HRMS-FAB: m/z = 267.0529 (calcd.
+
+
(
32.5) [M] , 122 (100).
267.0531 for C H NO Cl, [M+NH ] ).
12 8 3 4
ꢀ
4
-(4 -Chlorophenoxy)nitrobenzene (3) and (9)
2-(4-Chlorophenoxy)benzonitrile (5)
◦
1
◦
1
White solid, m. p. 75.8 – 76.1 C. – H NMR (400 MHz,
White solid, m. p. 85.0 – 85.7 C. – H NMR (400 MHz,
CDCl ): δ = 7.00 (4H, m), 7.38 (2H, dd, J = 6.8 Hz, J = CDCl ): δ = 6.85 (1H, d, J = 8.8 Hz), 7.01 (2H, m), 7.14
3
3
2.4 Hz), 8.20 (2H, d, J = 7.2 Hz, J = 2.4 Hz). – HRMS- (1H, t, J = 7.2 Hz), 7.35 (2H, m), 7.47 (1H, m), 7.66 (1H,
FAB: m/z = 267.0532 (calcd. 267.0531 for C12H NO Cl, dd, J = 8.0 Hz, J = 2.0 Hz). – HRMS-FAB: m/z = 247.0633
8
3
+
+
[
M+NH ] ).
(calcd. 247.0627 for C13H NOCl, [M+NH ] ).
8 4
4
ꢀ
ꢀ
4
-(2 -Chlorophenoxy)nitrobenzene (4) and (8)
2-(4 -Nitrophenoxy)nitrobenzene (6)
Yellow solid, m. p. 101.1 – 101.9 C. – 1H NMR
◦
1
◦
White solid, m. p. 76.8 – 77.0 C. – H NMR (400 MHz,
CDCl ): δ = 6.93 (2H, m), 7.16 (1H, dd, J = 8.0 Hz, J = (400 MHz, CDCl ): δ = 7.03 (2H, m), 7.23 (1H, dd, J =
.6 Hz), 7.23 (1H, dt, J = 8.0 Hz, J = 1.6 Hz), 7.33 (1H, 8.4 Hz, J = 1.2 Hz), 7.41 (1 H, dt, J = 8.0 Hz, J = 1.6 Hz),
3
3
1
dt, J = 8.0 Hz, J = 1.6 Hz), 7.51(1H, dd, J = 8.0 Hz, J = 7.67 (1 H, dt, J = 8.0 Hz, J = 1.2 Hz), 8.06 (1H, dd, J =
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1186
H. Xu – H.-F. Li · Arylmethanesulfonates / S Ar Reaction for K CO -mediated C(Aryl)–O Bond Formation
N
2
3
8
.0 Hz, J = 1.6 Hz), 8.22 (2H, m). – GC/MS (EI, 70 eV): m/z Acknowledgements
+
(
%) = 260 (9.9) [M] , 139 (53.8), 122 (100).
This work was supported by the Program for New Cen-
tury Excellent Talents in University (NCET), State Education
Ministry, China, the Scientific Research Foundation for the
Returned Overseas Chinese Scholars, State Education Min-
ꢀ
-(2 -Chlorophenoxy)nitrobenzene (7)
2
Pale yellow liquid. – 1H NMR (400 MHz, CDCl3): istry (No. 14110101), the Key Project of Chinese Ministry
δ = 6.83 (1H, dd, J = 8.4 Hz, J = 1.2 Hz), 7.07 (1H, of Education (No. 107105), and the Science & Technology
dd, J = 8.0 Hz, J = 1.6 Hz), 7.16 (3 H, m), 7.47 (2H, Research Plan in Shaanxi Province of China (No. 2006K01-
m), 7.97 (1H, dd, J = 8.0 Hz, J = 1.6 Hz). – HRMS- G31-04). We also acknowledge Northwest A&F University
FAB: m/z = 267.0535 (calcd. 267.0531 for C12H NO Cl, for the financial assistance within the program for excellent
8
3
+
[
M+NH ] ).
young talents (No. 01140301 and 01140402).
4
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2
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