Modified Glaser reaction of terminal alkynes on KF/Alumina

Article abstract of DOI:10.1007/s00706-005-0416-6

A variety of 1,3-diyne compounds are prepared in a solvent-free reaction on KF/alumina in the presence of catalytic amounts of Cu(OAc)₂· H₂O with up to 96% yields at room temperature. Springer-Verlag 2005.

Full text of DOI:10.1007/s00706-005-0416-6

Monatshefte f€ur Chemie 137, 213–217 (2006)
DOI 10.1007/s00706-005-0416-6
Modified Glaser Reaction of Terminal
Alkynes on KF/Alumina
Ali Sharifi1;ꢀ, Mojtaba Mirzaei1, and M. Reza Naimi-Jamal2;ꢀ
1
Chemistry and Chemical Engineering Research Center of Iran,
P.O. Box 14335-186, Tehran, Iran
2
Faculty of Chemistry, Iran University of Science and Technology,
Naarmak, 16846-11367 Tehran, Iran
Received May 4, 2005; accepted June 15, 2005
Published online December 15, 2005 # Springer-Verlag 2005
Summary. A variety of 1,3-diyne compounds are prepared in a solvent-free reaction on KF=alumina in
the presence of catalytic amounts of Cu(OAc)2 ꢁ H2O with up to 96% yields at room temperature.
Keywords. Glaser Reaction; Alkynes; Homocoupling; KF=Alumina; Solvent-free Synthesis.
Introduction
The Glaser reaction, first reported in 1869 [1] involves self-coupling of terminal
alkynes promoted by cupric salts. The resulting diacetylenes are important building
blocks in the synthesis of natural products [2], monomers, polymers, fundamental
host molecules [3], and supramolecular materials useful in electronic and optical
industries [4].
Traditionally, the classical oxidative dimerization is carried out in organic
solvents such as methanol, acetone, pyridine, cyclohexylamine, and toluene.
Recent procedures, however, focused on more environmentally friendly methods
applying supercritical fluids [5], water [6], and ionic liquids [7] to minimize using
of organic solvents. Efforts to completely eliminate the need for organic solvents
by carrying out the reaction on the surface of solid-supports have also been docu-
mented [8]. The active surface of some solid-supports including montmorillonite,
silica gel, clayfen, and alumina has been confirmed as a practical alternative to
organic solvents. The milder conditions, increased selectivity, decreased side reac-
tions, and eco-friendly conditions make this modern procedure more and more
attractive. Among others, alumina seems to be a particularly useful reagent, as it
can be modified in a variety of ways which enhance its application [9]. For exam-
ple KF=alumina developed by Ando et al. [10] has found a broad application in
ꢀ
Corresponding authors. E-mails: sharifi@ccerci.ac.ir, naimi@iust.ac.ir

214
A. Sharifi et al.
Scheme 1
organic reactions [11], such as elimination [12], addition [13], condensation [14],
and epoxidation [15]. Kabalka et al. have used this system for the homocoupling of
terminal acetylenes in a solvent-free reaction, enhanced by microwave irradiation
[8]. They have reported that the best reaction conditions for the Glaser reaction
using KF=alumina were found to be CuCl2 (3.7 eq) and KF=alumina (40% by
weight, 0.6 g) for one mmol terminal alkyne under microwave irradiation for
8 minutes. Although this method benefits from the solvent-free conditions, the use
of excess Cu catalyst for only good to moderate yields (up to 75%) suggests a
need for further improvement.
We have previously reported that this method can be modified by using of
catalytic amounts of a copper halide and alumina under microwave irradiation with
moderate yields [16]. We now wish to report that high to excellent yields can be
obtained, if the terminal acetylenes are treated on KF=alumina, in the presence of
Cu(OAc)2 ꢁ H2O and morpholine at room temperature (Scheme 1).
Results and Discussions
A variety of terminal alkynes including aliphatic and aromatic acetylenes, propar-
gylamines, and ethers were successfully coupled. The results are summarized in
Table 1.
All of the known products exhibit physical and spectral characteristics in
accord with literature values. The high yields show that this method is an efficient
approach to 1,3-diynes. For example, the treatment of phenylacetylene (1a) in
the presence of 0.2 eq Cu(OAc)2 ꢁ H2O on KF=alumina afforded the corresponding
1,4-diphenyl-1,3-butadiyne in 96% yield, obviously more than that reported by
Kabalka (75%) [8] under microwave irradiation and Glaser (40%) [1] by the
classical method in organic solvents. The more recent methods using ionic liquids
are hardly more efficient [7].
To assay the effect of any contributor in the reaction, we have chosen the
homoalkynylation reaction of phenylacetylene. The results are summarized in
Table 2. In the absence of morpholine and Cu-catalyst no reaction occurred on
KF=alumina (Entry 1). Addition of morpholine to KF=alumina raised the yield
of the reaction to 17% (Entry 2). Without morpholine but in the presence of
Cu-catalyst the yield is better (27%, Entry 3), but not high enough. As it is shown
in Table 2, the presence of KF=alumina seems to be necessary (Entry 4). The
best result was obtained by using KF=alumina, morpholine, and Cu(OAc)2 ꢁ H2O
together (Entry 5). These results were confirmed with the homocoupling reaction
of methyl-phenylprop-2-ynylamine (1b) and 4-(prop-2-ynyl)morpholine (1d)
(Table 2, Entries 6–11). Avoiding microwave irradiation and performing of these
reactions just at room temperature makes this method more attractive and practical.

Modified Glaser Reaction
215
Table 1. Oxidative homocoupling of terminal acetylenic compounds on KF=alumina at room tem-
perature
Entry
1
Substrate
No.
Product
No. Ref.
Yield=%
1a
2a [17]
96
2
3
1b
1c
2b [18]
2c [19]
92
93
4
5
1d
1e
2d [20]
2e [16]
90
90
6
1f
2f [21]
65
7
8
1g
1h
2g [16]
2h [22]
60
90
Table 2. The effects of reaction contributors
Entry
Alkyne
KF=Alumina
(1 g)
Morpholine
(1.2 mmol)
Cu(OAc)2 ꢁ H2O
Yield=%
(1.0 mmol)
(0.2 mmol)
1
2
1a
1a
1a
1a
1a
1b
1b
1b
1d
1d
1d
þ
þ
þ
ꢂ
þ
þ
ꢂ
þ
þ
ꢂ
þ
ꢂ
þ
ꢂ
þ
þ
ꢂ
þ
þ
ꢂ
þ
þ
ꢂ
ꢂ
þ
þ
þ
ꢂ
þ
þ
ꢂ
þ
þ
0
17
27
64
96
0
3
4
5
6
7
45
92
0
8
9
10
11
43
90

216
A. Sharifi et al.
In addition of mild conditions, the time of the reaction is short enough for pre-
parative purposes.
In summary, we have reported here a facile modified method of the Glaser
reaction for the preparation of 1,3-diynes from terminal acetylenes in a solvent-free
reaction at room temperature, with up to quantitative yields.
Experimental
KF=alumina was prepared as previously described [23]. Mps were determined on a hot stage or
1
oil bath apparatus. H and 13C NMR spectra were recorded on a Bruker 80 MHz in CDCl3 using
TMS as internal standard. All known products were characterized by comparison of their melting
points or NMR spectra with those in literature. The GC was performed with a Varian CP-3800
instrument.
General Procedure for Oxidative Homocoupling of Terminal Acetylenic
Compounds on KF=Alumina at Room Temperature
A mixture of 1 mmol acetylenic compound, 1.2 mmol morpholine, and 0.2mmol copper acetate
monohydrate were ground with 1 g KF=alumina in a mortar. The mixture was transferred to a
25cm3 flask and stirred for 3 h. The progress of reaction was monitored by TLC and GC. Then the
mixture was extracted with ethyl acetate. Evaporation of the solvent gave the crude product, which was
purified by flash column chromatography (silica gel; eluent: petroleum ether).
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