Efficient and recyclable reaction system for the homocoupling of terminal acetylenes

Article abstract of DOI:10.1080/00397910600781281

Diynes were synthesized in high yields by homocoupling of terminal arylacetylenes and terminal alkylacetylenes in Cu(OAc)₂-PEG (polyethyleneglycol) with NaOAc as a base. Cu(OAc)₂-PEG was readily recycled via solvent precipitation with efficient recyclability. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600781281

w
Synthetic Communications , 36: 2503–2511, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600781281
Efficient and Recyclable Reaction System
for the Homocoupling of Terminal
Acetylenes
Xiaoling Lu, Yuhong Zhang, Chengcai Luo,
and Yanguang Wang
Department of Chemistry, Zhejiang University, Hangzhou, China
Abstract: Diynes were synthesized in high yields by homocoupling of terminal aryla-
cetylenes and terminal alkylacetylenes in Cu(OAc) -PEG (polyethyleneglycol) with
2
NaOAc as a base. Cu(OAc)
with efficient recyclability.
2
-PEG was readily recycled via solvent precipitation
Keywords: Coupling of terminal acetylene, cupric salt, diyne, PEGs
Diynes are useful organic compounds and are widely applied in organic
[
1–5]
synthesis and materials science.
directed toward the coupling of terminal acetylenes.
methodology involves the oxidative coupling of acetylene derivatives
Much successful research has been
[6–9]
The conventional
[10–12]
[13]
employing cuprous salts–oxidizing agents
or cupric salts
in the
presence of amines. The reaction speed increases with the acidity of the acet-
ylenic proton, and the alkylacetylenes give poor coupling yields in some cases.
The presence of amines is indispensable for the reaction to occur. Recent
studies have shown that Pd(0)-Cu(I) could effectively catalyze the homo-
coupling of arylacetylenes in the presence of various additives such as chloro-
[14–24]
acetone, bromoacetone, allyl bromide, stoichiometric I , and so on,
2
albeit the alkylacetylenes were less effective under similar conditions.
Here we report a novel, facile procedure for the coupling of terminal
acetylenes by employing Cu(OAc) -PEG-NaOAc as the catalyst system. It
2
Received in Japan October 12, 2005
Address correspondence to Yuhong Zhang, Department of Chemistry, Zhejiang
University, Hangzhou 310027, China. E-mail: yhzhang@zjuem.zju.edu.cn
2
503

2
504
X. Lu et al.
was found that both alkylacetylene and arylacetylene showed high activity and
delivered excellent yields. The product was easily extracted after the reaction,
and the reaction system could be readily recycled more than five times with
only a small decrease in the activity (Scheme 1).
Our initial studies were focused on the optimization of the reaction con-
ditions for the homocoupling of the terminal alkynes. Phenylacetylene was
chosen as a model substrate for the optimization process. Several bases
were tested first on the model reaction (Table 1). It is known that amines,
such as pyridine and tetramethylenediamine, are indispensable for the
copper-promoted Glaser reaction to occur. However, among the bases tested
in our experiment, NaOAc was found to be most effective and afforded the
highest yield (Table 1, entry 6), albeit the use of pyridine and triethylamine
led to high yield as well (Table 1, entries 1, 2). Exchanging the bases to
K CO and K PO under the same conditions delivered the desired diyne
2
3
3
4
but in low yields (Table 1, entries 4, 5). DBU was almost inactive to the
reaction and delivered 2% of the expected diyne (Table 1, entry 3).
It was interesting that the chain length of PEG had a marked effect on the
reaction. PEG 6000 gave the highest efficiency (Table 1, entry 6). Replacing
the PEG source with PEG 4000 had a negative effect on the efficiency
(
Table 1, entry 7). Further decreasing of molecular weight of PEG induced
the drop of yield to 41% even though the reaction time was prolonged to
0 h (Table 1, entry 8). When PEG 10000 was employed as the reaction
2
medium, lower yield of 33% was obtained. A possible reason was that the
PEG 10000 was too sticky to be efficiently stirred. In addition, the low
reaction temperature caused the decreasing of product yield. For example,
the reduction of the reaction temperature to 80 8C had a dramatic effect on
the reaction with the yield being lowered to only 37% (Table 1, entry 10).
On the other hand, when the temperature was too high (Table 1, entries 11,
12), some by-products were formed, which brought on the impurity of
product and the reduction of the yields.
Table 2 presented the promoting effect of various copper salts in PEG
6000 at 120 8C with NaOAc as the base. Comparing with other copper salts,
Cu(OAc) exhibited the highest reactivity and delivered 98% of the desired
diyne. The amount of Cu(OAc) had a great influence on the homocoupling
2
2
reaction (Table 2, entries 5–8). Poor conversion and yield was observed
when the amount of Cu(OAc) was lower than 100 mol% (Table 2, entries
2
5, 6), which was consistent with the report of classical Glaser reaction.
Increasing the amount of Cu(OAc) to 150 mol% results in the enhancement
2
Scheme 1. Homocoupling of terminal acetylenes by Cu(OAc) in PEG.
2

Homocoupling of Terminal Acetylenes
2505
a
Table 1. Effects of chain length of PEG as well as base on the coupling reaction
b
Yield (%)
Entry
Base
PEG
Temp. (8C)
T (h)
1
2
3
4
5
6
7
8
9
C H N
5
6000
6000
6000
6000
6000
6000
4000
2000
10000
6000
6000
6000
120
120
120
120
120
120
120
120
120
80
12
20
12
12
12
12
20
20
20
20
12
12
83
98
2
6
Et
3
N
DBU
K CO
2
26
39
98
80
41
33
37
94
19
3
K PO
3
4
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
1
1
1
0
1
2
140
160
a
.
2 2
Reaction conditions: phenylacetylene (0.102 g, 1 mmol), Cu(OAc) H O (0.2 g,
1
mmol), base(1.5 mmol), PEG (4 g).
b
GC yield.
of the reaction speed, but some by-products appeared and the yield of diyne
was slightly decreased (Table 2, entry 8). Therefore, we used 100 mol%
Cu(OAc) as the optimized amount in the following reactions (Table 2,
2
entry 7).
With the optimized reaction conditions in hand, we next studied the
homocoupling of a variety of terminal alkynes. The results are summarized
in Table 3. It is seen that both the arylacetylenes and alkylacetylenes
delivered good to excellent isolated yields (Table 3, entries 1–3, 5, 6). The
properties of the substituted group in the aryl influenced the reactivity of
acetylenes. Both the electron-rich and the electron-poor arylacetylenes
a
Table 2. Catalytic effect of various copper salts
b
Yield (%)
Entry
Catalyst
Cu(NO
Cat. (%)
T (h)
1
2
3
4
5
6
7
8
3
)
2
100
100
100
100
5
20
20
20
20
20
20
12
10
36
41
23
7
Cu(acac)
CuCl2
CuI
2
Cu(OAc)
Cu(OAc)
2
2
3
75
55
98
93
Cu(OAc)2
Cu(OAc)
100
150
2
a
Reaction conditions: phenylacetylene (0.102 g, 1 mmol),
NaOAc (0.12 g, 1.5 mmol), PEG 6000 (4 g), 120 8C.
GC yield.
b

2
506
X. Lu et al.
Table 3. Homocoupling of terminal acetylenes by Cu(OAc)
a
NaOAc system
2
-PEG-
b
Entry
R
T(h)
Yield (%)
1
2
3
4
5
6
7
Ph
4-F-Ph
12
18
30
5
98
87
89
95
2
4-C H
5
-Ph
Cyclohex-1-enyl
n-C H
c
20
20
18
96
4
6
9
n-C
CH
H
13
98
86
2
OH
a
.
2 2
Reaction conditions: terminal alkyne (2 mmol), Cu(OAc) H O (0.4 g,
2
mmol), NaOAc (0.25 g, 3 mmol), PEG 6000 (6 g), 120 8C.
Isolated yield.
b
c
Reaction temperature was 90 8C.
delivered the desired products in good to excellent yields, but longer reaction
time was required (Table 3, entries 2, 3). 1-Ethynylcyclohexene showed the
best reactivity, and 95% yield was obtained within 5 h (Table 3, entry 4).
1-Hexyne gave impure products at 120 8C, but excellent yield was afforded
at 90 8C for 20 h (Table 3, entry 5). 1-Octyne had a good isolated yield
within 18 h of reaction time. The 100% conversion was achieved for
propargyl alcohol within 18 h, and a good yield was obtained as well
(
Table 3, entry 7).
The facile separation of the product by diethyl ether extraction allowed us
to test the effect of reusability of the reaction system. The coupling of pheny-
lacetylene was employed as a model reaction. Et N was proven to be more
3
efficient in recycling the catalyst as a base, albeit NaOAc provided the best
conversion in the first run. The residue after the extraction by diethyl ether
was subjected to a second run of the Glaser reaction by charging with the
same substrates under the same reaction conditions. However, the activity
of the recycling reaction decreased rapidly (Table 4, entries 1–3). We
noticed that during the reaction, the color of the reaction solution changed
from blue to yellow, and the floccules were observed at the bottom of the
flask when the magnetic stirrer was stopped. A yellow solid was separated
after the washing of the residue with toluene. The diffraction lines at
2
the analysis of X-ray diffractogram, showing that pure Cu O was formed
u ¼ 29.56, 36.42, 42.32, 52.40, 61.40, 73.64, and 77.468 were observed by
2
(
Fig. 1). To fulfil the transformation of Cu O to Cu(OAc) , the acetic acid
2 2
was added into the residue, and the mixture resulted was heated with
stirring at 80 8C for 1 h in air. In this case, the yellow solid reacted, and a
blue solution resulted. After the removing the acetic acid by extraction of

Homocoupling of Terminal Acetylenes
Table 4. Recycling of glaser reaction by Cu(OAc)
2507
a
2
-PEG
b
Yield (%)
Entry
Cycle
Conv. (%)
1
2
3
4
5
6
7
1
2
3
100
100
92
98
85
47
97
91
86
81
c
2
100
95
c
3
c
4
92
89
c
5
a
Reaction conditions: phenylacetylene (0.102 g, 1 mmol),
Et N (0.15 g, 1.5 mmol), PEG 6000 (5 g), 120 8C.
3
b
GC yield.
The residue after the extraction was treated by acetic
acid and reused as catalyst.
c
ethyl ether, the solution was used in the next run. Surprisingly, high reactivity
was observed (Table 4, entry 4). It is important to note that the reaction system
could be recycled five times with only a small decrease in activity with the
treatment of acetic acid in every cycle (Table 4, entries 4–7).
[
25]
Based on the reported Glaser reaction procedure,
mechanism that reconciles most of the experiment is proposed in Scheme 2.
a possible
–
This involves first the formation of RC ;; C in the presence of the base.
Then oxidative coupling happens, generating the coupling product and
Cu O in PEG. The regeneration of Cu(OAc) can be fulfilled by oxidation
2
2
of Cu O under air in the presence of the acetic acid.
2
In conclusion, we have shown that Cu(OAc) -PEG-NaOAc can be used as
2
a highly efficient reaction system for the coupling of both arylacetylenes and
alkylacetylenes in the absence of other organic solvents. Cu(OAc) -PEG can
be recycled effectively, which is the first example for recycle of Glaser reaction.
2
Figure 1. Powder X-ray diffraction pattern of the Cu O.
2

2
508
X. Lu et al.
Scheme 2. Possible recycle mechanism.
EXPERIMENTAL
Material
Phenylacetylene, 1-hexyne, 1-octyne, and propargyl alcohol were purchased
from ACROS, 1-ethynyl-4-fluorobenzene, 1-ethynylcyclohexene, and
1-ethynyl-4-ethylbenzene were purchased from Aldrich Chemical Company.
All of the solvents used were analytical grade or were purified according to
standard procedures.
Typical Procedure
General Procedure for the Homocoupling of Terminal Alkynes
PEG 6000 (6 g) was charged in a 25-mL flask and heated to 120 8C. Then
.
Cu(OAc)2 H O (2 mmol, 0.4 g), NaOAc (3 mmol, 0.25 g), and alkynes
2
(
2 mmol) were added, and the reaction mixture was stirred at 120 8C for the
indicated times. After cooling, the reaction mixture was extracted by diethyl
ether (3 Â 15 mL). GC 6890 and 6890GC-5973MS were performed to
analyze the combined organic extract. The crude product was purified by
flash chromatography on silica to give the pure product. NMR spectra were
recorded at 500 MHz on a Bruker Advance 500 spectrometer, using CDCl3
as the solvent and TMS as an internal standard. Mass spectroscopy data of
the products were collected on an MS-EI instrument. The gas chromatography
analysis was performed on an HP GC-6890 instrument.
Recycle Experiment
.
Cu(OAc)2 H O (0.2 g, 1 mmol) was dissolved in PEG 6000 (5 g), and Et N
2
3
(
0.15 g, 1.5 mmol) and phenylacetylene (0.102 g, 1 mmol) were added at
20 8C. The resulting solution was stirred at this temperature for 20 h. After
cooling, diethyl ether (3 Â 10 mL) was added to extract product.
1

Homocoupling of Terminal Acetylenes
2509
The residue after the extraction was subjected to acetic acid (0.18 g, 3 mmol),
and the mixture was heated in stirring at 80 8C for 1 h in air. The yellow solid
reacted, and a blue solution resulted. After cooling, the residual acetic acid
was removed by washing with diethyl ether (2 Â 10 mL). The remnant was
used in the next run as the catalyst by charging with the same substrate of phe-
nylacetylene (0.102 g, 1 mmol) and Et N (0.15 g, 1.5 mmol) without the
3
addition of Cu(OAc) and PEG 6000.
2
SUPPLEMENTARY DATA
[
27] 1
1
7
,4-Diphenylbutadiyne (T3-1).
.54–7.52 (m, 4 H), 7.37–7.32 (m, 6 H). C NMR (125 MHz, CDCl3,
H NMR (500 MHz, CDCl , TMS): d
3
1
3
TMS): d 132.6, 129.3, 128.7, 121.9, 81.9, 74.2. MS (EI): m/z (%): 202
100), 174 (4.6), 150 (6.9), 101 (12.7), 88 (5.8).
(
[
27]
1
1
CDCl , TMS): d 7.52–7.50 (m, 4 H), 7.05–7.02 (m, 4 H). C NMR
,4-bis(4-Fluorophenyl)buta-1,3-diyne (T3-2).
H NMR (500 MHz,
1
3
3
(
100 MHz, CDCl , TMS): d 163.0 (d, J ¼ 251.5 Hz), 134.5 (d, J ¼ 9.4 Hz),
3
1
17.7 (d, J ¼ 3.5 Hz), 115.9 (d, J ¼ 21.8 Hz), 80.4, 73.5. MS (EI): m/z
(
%): 238 (100), 218 (7.8), 119 (11.9).
[17]
1
1
,4-bis(4-Ethylphenyl)buta-1,3-diyne (T3-3).
H NMR (500 MHz,
CDCl , TMS): d 7.45 (d, J ¼ 8.1 Hz, 4 H), 7.17 (d, J ¼ 8.1 Hz, 4 H), 2.67
3
1
3
(
q, J ¼ 7.6 Hz, 4 H), 1.23 (t, J ¼ 7.6 Hz, 6 H). C NMR (125 MHz, CDCl ,
3
TMS): d 144.5, 129.8, 125.7, 117.1, 80.3, 72.0, 27.5, 13.6. MS (EI): m/z
(%): 258 (100), 243 (91.2), 228 (43.5), 129 (4.3), 114 (20.1).
[
17] 1
1
TMS): d 6.25–6.24 (m, 2 H), 2.12–2.10 (m, 8 H), 1.65–1.57 (m, 8 H).
,4-Dicyclohexenylbuta-1,3-diyne (T3-4).
H NMR (500 MHz, CDCl3,
1
3
C NMR (125 MHz, CDCl , TMS): d 138.2, 119.9, 82.8, 71.8, 28.5, 25.2,
3
2
2.4, 21.5. MS (EI): m/z (%): 210 (100), 181 (12.1), 167 (36.5), 152
28.7), 141 (27.9), 128 (26.0), 115 (27.8), 91 (14.5).
(
[
26] 1
Dodeca-5,7-diyne (T3-5).
H NMR (500 MHz, CDCl , TMS): d 2.25
3
(
(
t, J ¼ 6.9 Hz, 4 H), 1.52–1.47 (m, 4 H), 1.43–1.39 (m, 4 H), 0.90
1
3
t, J ¼ 7.3 Hz, 6 H). C NMR (125 MHz, CDCl , TMS): d 77.5, 65.6, 31.4,
3
27.6, 20.3, 14.3. MS (EI): m/z (%): 162 (68.9), 147 (4.5), 133 (4.2), 119
17.9), 105 (87.2), 91 (100).
(
[
26] 1
7
(
,9-Hexadecadiyne (T3-6).
t, J ¼ 7.0 Hz, 4 H), 1.53–1.26 (m, 16 H), 0.88 (t, J ¼ 6.9 Hz, 6 H).
NMR (125 MHz, CDCl , TMS): d 77.4, 65.2, 31.6, 28.9, 28.5, 22.5,
H NMR (500 MHz, CDCl , TMS): d 2.24
3
1
3
C
3
1
9.1, 14.0. MS (EI): m/z (%): 218 (3), 189 (38), 147 (36.7), 133
42.1), 119 (100).
(

2
510
X. Lu et al.
[
26] 1
Hexa-2,4-diyne-1,6-diol (T3-7).
d 5.39 (br, 2 H), 4.14–4.17(m, 4 H). C NMR (125 MHz, CDCl , TMS):
H NMR (500 MHz, CDCl , TMS):
1
3
3
3
d 79.6, 68.1, 49.5. MS (EI): m/z (%): 110 (72.7), 92 (7.8), 81 (89.7), 53
(
100), 39 (87.2).
ACKNOWLEDGMENT
We thank the Natural Science Foundation of China (no. 20373061).
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