Glaser coupling reaction in supercritical carbon dioxide

Article abstract of DOI:10.1039/a908014g

It is demonstrated for the first time that Glaser coupling can be carried out smoothly in supercritical carbon dioxide using a solid base (NaOAc) instead of amines.

Full text of DOI:10.1039/a908014g

Glaser coupling reaction in supercritical carbon dioxide
Jinheng Li and Huanfeng Jiang*
Guangzhou Institute of Chemistry, Chinese Academy of Sciences, PO Box 1122, Guangzhou 510650, China.
E-mail: jhf@mail.gic.ac.cn
Received (in Cambridge, UK) 5th October 1999, Accepted 18th October 1999
It is demonstrated for the first time that Glaser coupling can
be carried out smoothly in supercritical carbon dioxide using
a solid base (NaOAc) instead of amines.
in scCO2 consisted of CuCl2 (2 mmol), NaOAc (2 mmol),
MeOH (1 ml) and CO2 (14 MPa) at 40 °C.† Other terminal
acetylenes besides phenylacetylene were employed success-
fully using the optimized conditions (entries 9–12, Table 1).
The coupling reaction gave low conversion and yield in pure
scCO2 (entry 1, Table 1), in which CuCl2 and NaOAc cannot
dissolve (entries 1, 4 and 7, Table 2). It has been reported that
some organic or inorganic compounds, so-called ‘modifiers’,
can be added to the supercritical fluids to increase its solvent
power.11 Our results indeed show that the presence of MeOH
remarkably enhanced the rate of the reaction (entries 1 and 6,
Table 1). We further examined the solubility of different
reagents in different solvents in scCO2 and the results were
summarized in Table 2. MeOH, as modifier or co-solvent,
increased the solubility of CuCl2 and NaOAc in scCO2 (entries
3, 6 and 8, Table 2).2,3,11,12 Increasing the amount of MeOH to
3 ml in the reaction, decreased the rate and the yield to a small
extent. It is of interest to note that if only MeOH was used as
solvent, both the rate and the yield decreased and the reaction
was not clean (entry 2, Table 1). These results imply that scCO2
and MeOH are of the same importance to the reaction. The low
viscosity of scCO2 allows the products (diacetylenes) to diffuse
away from CuCl2 and NaOAc, while the proper amounts of
MeOH makes CuCl2 and NaOAc partially dissolve in scCO2,
although excess MeOH may affect the diffusion of the
products.
Considerable attention has recently been focused on using
supercritical carbon dioxide (scCO2) as a medium for organic
reactions.1–3 As a solvent the attractive physical and toxico-
logical properties of scCO2 have made it superior to conven-
tional organic solvents with regard to environmental con-
siderations.
Diacetylenes are central to many biological and polymer
molecules.4–8 Many of the most useful methods for the
synthesis of diacetylenes8–10 involve cupric salt promoted
coupling reactions, Glaser first observed that terminal acet-
ylenes underwent oxidative coupling to diacetylenes with CuCl
in the presence of NH4OH. Subsequent studies have shown that
a variety of cupric salts or oxygen in the presence of cuprous
salts can be employed. The oxidation has the further advantage
of solvent versatility. Water, methanol, Methyl Cellosolve,
acetone, pyridine, cyclohexylamine and toluene have all been
used as solvents for the reaction with nearly equal success.
Amines, most frequently pyridine and tetramethylenediamine,
are required in almost all CuII-promoted Glaser coupling.
However, amines often have unpleasant smells and flavors. The
present study is the first demonstration that Glaser coupling can
be carried out in the presence of CuCl2 in scCO2 using NaOAc
instead of amines (Scheme 1).
The pressure of CO2 also affected the reaction rate to some
extent. Our results indicate that a higher CO2 pressure is
preferable (entries 5 and 6, Table 1).
In earlier studies, when cupric chloride or cupric acetate was
added as a promoter, an organic base (pyridine) was usually
added to retain CuCl2 or Cu(OAc)2 in solution as complexes or
solvates and to catch the acid liberated during the coupling
reaction. In scCO2, to our surprise, the coupling took place
without base with higher conversion and yield than those in the
presence of pyridine (entries 3 and 4, Table 1). When NaOAc
Scheme 1
Our investigation began with an effort to optimize reaction
conditions for the oxidation coupling of terminal acetylenes
using CuCl2 and NaOAc. Phenylacetylene was chosen as a
model substrate for the optimization process (entries 1–8, Table
1). The final optimized reaction conditions for Glaser coupling
Table 2 Solubility of related reagents in different solventsa
Reagentsb
Solvent
Solubility
a
Table 1 Oxidation coupling of terminal acetylenes in scCO2
Entry
Conv.
(%)b
Isolated yield
(%)
1
2
3
4
5
6
7
8
9
CuCl2
CuCl2
CuCl2
NOAc
NOAc
NOAc
CuCl2/NOAc
CuCl2/NOAc
CuCl2/NOAc
Pyridine
CuCl2/pyridine
scCO2
MeOH
MeOH/scCO2
scCO2
MeOH
MeOH/scCO2
scCO2
MeOH/scCO2
MeOHc
insoluble
soluble
partial
insoluble
partial
partial
insoluble
partial
Run Alkyne
Base
t/h
1c
2d
3
PhC·CH
NaOAc
NaOAc
none
4
4
4
4
4
3
3
3
4
5
4
4
12
81
63
50
99
100
78
10
39
50
44
98
100
73
96
95
92
71
93
PhC·CH
PhC·CH
4
PhC·CH
pyridine
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
5e
6
PhC·CH
PhC·CH
soluble
soluble
partiald
7f
8g
9
PhC·CH
10
11
scCO2
MeOH
PhC·CH
98
C5H11C·CH
C6H13C·CH
HC·CCH2OH
100
100
100
100
a The procedure for determining solubility in scCO2: The desired amount of
the related reagents was placed in a 25 ml stainless steel cell. The cell was
sealed and filled with liquid carbon dioxide (14 MPa). The cell was then
heated to 40 °C for the desired time and the solubility of the related reagents
was monitored by viewing through a sapphire observation window.
Amounts of reagents: CuCl2 = 269 mg, NaOAc = 164 mg, pyridine =
158 mg. Amounts of solvent: scCO2 = 14 MPa, MeOH = 1 ml. 10 ml.
d The solubility of solid in this experiment is more than that of entry 8.
10
11
12
HC·CCH2OAc NaOAc
a Alkyne (1 mmol), CuCl2 (2 mmol), base (2 mmol), MeOH (1 ml), PCO
14 MPa, 40 °C. b Determined by GC analysis. c Did not add MeOH. d Only
used MeOH (10 ml) as solvent. PCO = 7.5 MPa. Added 1 mmol of
=
2
b
e
f
c
2
CuCl2. g Added 3 ml of MeOH.
Chem. Commun., 1999, 2369–2370
This journal is © The Royal Society of Chemistry 1999
2369

Liquid CO2 was then transferred into the autoclave to the desired pressure.
The reaction mixture was stirred at 40 °C for 3–5 h. After the reaction, the
CO2 was vented and the surplus was extracted with Et2O. The conversion
was determined by GC using an internal standard. The product was then
purified by preparative TLC on silica gel using light petroleum–EtOAc
(10+1) as eluent.
was added, the reaction gave a satisfactory result (entry 6, Table
1). It is clear that NaOAc is superior to pyridine in scCO2. The
results in Table 1 also show that a sufficient amount of cupric
chloride is necessary for the Glaser coupling (entries 6 and 7,
Table 1).
At least two reaction pathways had been proposed in earlier
reports.8a,d One involves a radical mechanism and the other
formation of a cupric complex. We used two radical traps (N-
tert-butylbenzylideneamine N-oxide and 2-methyl-2-nitroso-
propane) in the reaction, but we did not detect any radicals.
Base on the results shown in Tables 1 and 2, we could
conclude several points. (i) In scCO2, the presence of NaOAc
plays an important role in enhancing the reaction rate. (ii) A
sufficient amount of cupric chloride is necessary for the Glaser
coupling. (iii) the low viscosity of scCO2 favors the oxidation
coupling reaction of terminal acetylenes. (iv) Addition of a
correct amount of MeOH can increase the dissolution of CuCl2,
and enhance the rate of the reaction.
In summary, we have observed that Glaser coupling reactions
can proceed smoothly in scCO2 in good yields. Of particular
note is the fact that this new Glaser coupling reaction is more
environmentally friendly than the traditional reaction and shows
potential utility in industry. The mechanism and applications of
the reaction are currently under investigation in our labo-
ratory.
1 P. G. Jessop, T. Ikariya and R. Noyori, Chem. Rev., 1999, 99, 475.
2 L. Jia, H. Jian and J. Li, Green Chem., 1999, 91.
3 L. Jia, H. Jiang and J. Li, Chem. Commun., 1999, 985.
4 F. Bohlmann, F. T. Burkhart and C. Zero, Naturally Occurring
Acetylenes, Academic Press, London and New York, 1973.
5 L. Hansen and P. M. Boll, Phytochemistry, 1986, 25, 285.
6 Y. S. Kim, S. H. Jin, S. L. Kim and D. R. Hahn, Arch. Pharm. Res.,
1989, 12, 207.
7 H. Matsunaga, M. Katano, H. Yamamoto, H. Fujito, M. Mori and K.
Tukata, Chem. Pharm. Bull., 1990, 38, 3480.
8 Review: (a) R. A. Raphael, E. C. Taylor and H. Wynberg, Advances in
Organic Chemistry, Mack Printing CO, Easton, PA, New York, 1963,
vol. 4, pp. 225–328; (b) W. S. Trahanovsky, Oxidation in Organic
Chemistry, Academic Press, New York and London, 1973, vol. 5-B, p.
1; (c) M. Hudlicky, Oxidation in Organic Chemistry, ACS Monograph
186, Washington DC, 1990, p. 58; (d) H. G. Viehe, Chemistry of
Acetylenes, Marcel Dekker, New York, 1969, p. 597; (e) K. Sonoga-
shira, in Comprehensive Organic Synthesis, ed. B. M. Trost and I.
Fleming, Pergamon, Oxford, 1991, vol. 3, p. 551.
9 R. Rossi, A. Carpita and C. Bigelli, Tetrahedron Lett., 1985, 26, 523.
10 S. Kenkichi, T. Yasuo and H. Nobue, Tetrahedron Lett., 1985, 26,
523.
11 J. A. Darr and M. Poliakoff, Chem. Rev., 1999, 99, 495.
12 A. Francis, J. Phys. Chem., 1954, 58, 1099; J. B. Ellington, K. M. Park
and J. F. Brennecke, Ind. Eng. Chem. Res., 1994, 33, 965.
We thank the National Natural Science Foundation of China
for financial support (No. 29772036 and 29872039) and Dr
Fanglu¨ Huang for helpful discussion. We also thank Professor
Buxing Han (Beijing Institute of Chemistry, Chinese Academy
of Sciences) for providing the reaction cell.
Notes and references
† Typical procedure: To a mixture of CuCl2 (2 mmol) and NaOAc (2 mmol)
in an HF-25 autoclave, MeOH (1 ml) and alkyene (1 mmol) were added.
Communication 9/08014G
2370
Chem. Commun., 1999, 2369–2370