Coupling reaction of acid chlorides with terminal alkynes catalyzed by diatomite-supported palladium(II) salophen complex

Article abstract of DOI:10.2174/157017811795685117

A highly-efficient method for the copper- and solvent-free coupling reaction of acid chlorides and terminal alkynes catalyzed by diatomite-supported palladium(II) salophen complex is described. Acid chlorides are easily coupled with terminal alkynes, givi

Full text of DOI:10.2174/157017811795685117

364
Letters in Organic Chemistry, 2011, 8, 364-367
Coupling Reaction of Acid Chlorides with Terminal Alkynes Catalyzed by
Diatomite-Supported Palladium(II) Salophen Complex
Mohammad Bakherad*, Ali Keivanloo, Bahram Bahramian, Zahra Kalantar and
Faezeh N. Ashrafi
School of Chemistry, Shahrood University of Technology, Shahrood, Iran
Received October 15, 2010: Revised March 31, 2011: Accepted March 31, 2011
Abstract: A highly-efficient method for the copper- and solvent-free coupling reaction of acid chlorides and terminal
alkynes catalyzed by diatomite-supported palladium(II) salophen complex is described. Acid chlorides are easily coupled
with terminal alkynes, giving good to high yields in the presence of a low catalyst loading (1 mol% Pd) in DIEA at room
temperature under aerobic conditions. After centrifugation, the supported catalyst is able to be recycled and reused for
several times with only a slight decrease in activity.
Keywords: Copper-free, sonogashira reaction, supported catalyst, acid chlorides.
Alkynyl ketones are useful synthetic intermediates for the
preparation of many biologically active compounds and
heterocyclic derivatives [1]. The direct coupling of alkynyl
palladium reagents with acid chlorides is an important
method for the preparation of alkynyl ketones. However,
these methods require anhydrous solvents and an inert
atmosphere [2]. Moreover, these reactions require degassed
organic solvents, and have to be carried out under an inert
atmosphere. This is particularly inconvenient when the
reactions are carried out in multiple vessels for library
generation. In spite of the synthetic elegance of the
construction of synthetically useful alkynyl ketones, these
palladium-catalyzed reactions are usually carried out in a
homogeneous phase, which makes the catalysts difficult to
recover and reuse in subsequent reactions Hence, facile
separation of catalysts and products for the recycling of the
catalysts is rather important from the viewpoints of
economical and environmental concern. For these reasons,
heterogenization of such homogeneous catalysts used for
alkynyl ketones formation is very valuable.
Very recently, we have reported the synthesis of the
polystyrene-supported bidentate phosphine palladium(0)
complex [PS-dpp-Pd(0)] and found that this complex is a
highly active and recyclable catalyst for acylation of terminal
alkynes with acid chlorides [5]. However, to the best of our
knowledge, no Sonogashira coupling reaction of acid
chlorides with terminal alkynes catalyzed by diatomite-
supported palladium(II) salophen complex has been
reported.
Diatomite (SiO2·nH2O) or diatomaceous earth is a
siliceous rock made up largely from the skeletons of aquatic
plants called diatoms [6]. Due to the extremely porous
structure, low density and high surface area of diatomite,
there is a possibility to use it for the adsorption of organic
and inorganic chemicals. Furthermore, these unique
properties have led to its applications as filtration media in a
number of industries. The diatom shell, which is composed
of amorphous silica, has properties such as high porosity
with strong adsorb ability and excellent thermal resistance.
Hence, diatomite has been widely used as filter aid, catalytic
support, and adsorbent [7].
The use of heterogeneous catalysts for synthesis of
alkynyl ketones has paid much attention to reducing waste,
thus working toward an environmentally benign chemical
process. Likhar and co-workers [3] have reported that acid
chlorides could be coupled with terminal alkynes in the
presence of 1 mol% of Pd/C under refluxing toluene, and the
catalyst could be reused for five cycles with a 15% leaching
of Pd.
In the present study, we wish to report the synthesis of
diatomite-supported palladium(II) salophen complex and its
catalytic properties in the copper- and solvent-free
Sonogashira reaction of acid chlorides with terminal alkynes
catalyzed under aerobic conditions.
The synthesis of the diatomite-supported Pd(II) salophen
complex was carried out using a slight modification of the
procedure previously reported for the synthesis of diatomite-
supported Mn(II) salophen [8]. Specifically, 2.0 g of
diatomite was added to 100 ml of ethanol together with 10.0
mmol of PdCl2(PhCN)2. After the mixture was refluxed for 6
h, 10.0 mmol of salophen was added to the suspension, and
the mixture was further refluxed for 12 h. Then the mixture
was cooled to room temperature, filtrated, and washed with
ethanol. The catalyst was then obtained by drying the solid
under vacuum at 100 °C for 12 h. The palladium content of
diatomite-supported Pd(II) salophen, which was determined
Recently Chen et al. [4] have described the synthesis of
alkynyl ketones by coupling acid chlorides with terminal
alkynes catalyzed by a nanosized MCM-41 anchored
palladium bipyridyl complex in the presence of PPh3 and CuI
at 50 °C in Et3N as a solvent.
*Address correspondence to this author at the School of Chemistry,
Shahrood University of Technology, Shahrood, Post Code: 3619995161,
Iran; Tel/Fax: +982733395441; E-mail: m.bakherad@yahoo.com
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

Coupling Reaction of Acid Chlorides with Terminal Alkynes Catalyzed
Letters in Organic Chemistry, 2011, Vol. 8, No. 5
365
by inductively coupled plasma (ICP), was obtained to be
3.38 %. A comparison of the FT-IR spectrum for the
encapsulated complex with that of the ‘‘free complex’’ [8]
indicates the presence of the complex inside the diatomite
cavities and pores. The IR spectra for diatomite-supported
Pd(II) salophen show major bands at 3400, 3050, 1610,
1570, 1530, 1100, and 790 cm-1 which are absent in the
diatomite IR spectrum.
phenylacetylene under similar conditions to afford the
corresponding products 3d, 3e in excellent yield (99%).
The Sonogashira coupling reaction of the ortho-
substituted electron rich benzoyl chlorides with terminal
alkynes gave the corresponding coupling products in high
yields owing to the steric hindrance of the ortho-substituents
(entries 3 and 13).
When the less reactive acetylene, 1-hexyne, and 1-octyne
were used, the coupling product was produced efficiently.
The coupling of para-substituted benzoyl chlorides having
methyl, methoxy, and chloro groups took place with 1-
hexyne to give the corresponding products 3j-l in 96%, 97%,
and 99% yields, respectively (entries 10-12). Coupling
reaction of 1-octyne with more reactive electron-
withdrawing p-chlorobenzoyl chloride or the less active
electron-rich p-methyl and p-methoxybenzoyl chlorides gave
a high yields (entries 17-19). A hetero-aryl acid chloride
such as 2-thiophene carbonyl chloride reacted with terminal
alkynes to give the good products (entries 8, and 15). Under
the same conditions as above, cyclohexane acid chloride also
afforded the desired product in good to excellent yields
(entries 7, 14, and 20).
The diatomite-supported Pd(II) salophen complex
prepared was first used in the Sonogashira coupling reaction
of acid chlorides with terminal alkynes. The coupling
reaction of benzoyl chlorides with phenylacetylene was
initially studied as a model reaction. The reaction conditions
were systematically optimized, and the results were
presented in Table 1. As shown in this table, our initial goal
was to optimize the reaction conditions for a copper- and
solvent-free coupling of benzoyl chloride 1a (1 mmol) and
phenylacetylene 2a (1mmol) in the presence of 1.0 mol% Pd.
When the reaction was performed with DIEA as base, an
excellent 98% yield of the product was obtained (entry 2).
Increasing the amount of palladium catalyst (entry 8) and
increasing the reaction time (entry 9) did not increase the
yield of product further. Decreasing the reaction time (entry
10) decreased the yield of product. A low palladium
concentration prolonged the reaction time and gave a
decreased yield (entry 11).
The recyclability of the diatomite-supported Pd(II)
salophen complex was examined in the coupling reaction of
benzoyl chloride and phenylacetylene. The catalyst was
separated from the reaction mixture by filtration after each
experiment, washed with water and acetonitrile, and dried
carefully before use in subsequent runs. Thus after the first
reaction, which gave a quantitative yield of the coupling
product 3a (Table 2, entry 1), the catalyst beads were
recovered and successively subjected to four further runs
under the same conditions to afford 3a in 97_85% yields
(Table 3). It is to be mentioned that some information
included in this article has previously been published [9].
After the optimized conditions were found, we explored
the general applicability of the diatomite-supported Pd(II)
salophen complex as a catalyst for copper- and solvent-free
coupling reaction of acid chlorides 1 containing electron-
withdrawing or donating substituents with different alkynes
2. The results are shown in Table 2. The coupling reaction of
phenylacetylene with p-methyl and p-methoxy benzoyl
chlorides bearing electron-donating groups at their para-
positions gave the corresponding products 3b and 3f in 99%
and 95% yields respectively (entries 2 and 6). p-nitro and p-
chloro benzoyl chlorides having electron- electron-deficient
aromatic rings also underwent the coupling reaction with
In conclusion, we have shown that diatomite-supported
palladium(II) salophen complex is a highly efficient and
recyclable catalyst for the copper- and solvent-free coupling
Table 1. Copper-and Solvent-Free Coupling Reaction of Benzoyl Chloride with Phenylacetylenea
Entry
Base
Catalyst (mol%)
Time (h)
Yieldb (%)
1
2
Et3N
DIEAc
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
1.0
1.0
0.5
2
2
2
2
2
2
2
2
5
1
5
97
98
97
65
97
95
93
98
98
86
91
3
Pyrrolidine
Pyridine
Piperidine
Morpholine
Et2NH
4
5
6
7
8
DIEA
9
DIEA
10
11
DIEA
DIEA
aReaction conditions: benzoyl chloride (1.0 mmol), phenylacetylene (1.0mmol), base (1.0 mmol), room temperature, aerobic conditions.
bGC yield.
cDiisopropylethylamine.

366 Letters in Organic Chemistry, 2011, Vol. 8, No. 5
Bakherad et al.
Table 2. Copper- and Solvent-Free Sonogashira Reactions of Aroyl Chlorides with Terminal Alkynesa
diatomite-supported
Pd(II)salophen complex
R
COAr
ArCOCl
R
+
DIEA, 2 h, r. t.
3
1
2
Entry
Ar
R
Product
Yieldb (%)
1
2
Ph
Ph
3a
3b
3c
3d
3e
3f
98
99
98
99
99
95
91
92
97
96
97
99
95
98
94
99
99
95
94
99
4-Me-C6H4
2-Me-C6H4
4-NO2-C6H4
4-Cl-C6H4
4-MeO-C6H4
cyclohexyl
2-thiophen
Ph
Ph
3
Ph
4
Ph
5
Ph
6
Ph
7
Ph
3g
3h
3i
8
Ph
9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C6H13
n-C6H13
n-C6H13
n-C3H7
10
11
12
13
14
15
16
17
18
19
20
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
2-Me-C6H4
cyclohexyl
2-thiophen
4-NO2-C6H4
4-Cl-C6H4
4-Me-C6H4
4-MeO-C6H4
cyclohexyl
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
aReaction conditions: 1 (1.0 mmol), 2 (1.0 mmol), diatomite-supported palladium (II) salophen complex (0.01 mmol), DIEA (1 mmol), 2 h, room temperature, aerobic conditions.
bGC yield.
Table 3. Sonogashira Coupling Reaction of Benzoyl Chloride with Phenylacetylene Catalyzed by the Recycled Catalysta
Entry
Catalyst
Yield(%)
1
2
3
4
first cycle
second cycle
third cycle
97
95
91
85
fourth cycle
aReaction conditions; benzoyl chlorid (1.0 mmol), phenylacetylene (1.0 mmol), catalyst (0.01 mmol), Et3N (1 mmol), room temperature, 2 h, aerobic conditions.
bGC yield.
reaction of a variety of acid chlorides and terminal alkynes
leading to the formation of alkynyl ketones. The catalyst can
be easily recycled by centrifugation and reused for several
times with only a slight decrease in activity.
Then 10.0 mmol (0.318 g) of salophen was added to the
suspension, and the mixture was further refluxed for 12 h.
The resulting product was filtered, washed with ethanol, and
dried at 100 °C for 12 h to give diatomite-supported Pd(II)
salophen complex.
Typical Procedure for the Preparation of Diatomite-
Supported Pd(II) Salophen Complex
Typical Procedure for the Coupling Reaction of Acid
Chlorides with Terminal Alkynes Catalyzed by
Diatomite-Supported Palladium(II) Salophen Complex
To a 250-ml round bottom flask equipped with a
magnetic stirrer bar, and containing EtOH (100 ml), were
added 2.0 g of dried diatomite and 10.0 mmol (0.383 g) of
PdCl2(PhCN)2, and the reaction mixture was refluxed for 6 h.
A round bottom flask was charged with an acid chloride
(1.0 mmol), a terminal alkynes (1.0 mmol), catalyst (0.01

Coupling Reaction of Acid Chlorides with Terminal Alkynes Catalyzed
Letters in Organic Chemistry, 2011, Vol. 8, No. 5
367
cyclohydrocarbonylation of ꢀ-keto alkynes catalyzed by
a
mmol), and DIEA (1.0 mmol). The mixture was stirred at
room temperature for 2 h under aerobic conditions. Upon
completion of the reaction, the reaction mixture was
dissolved in chloroform (5 ml). The palladium catalyst was
separated from the mixture by filtration, washed with water
(10 ml) and acetonitrile (10 ml), and reused in the next run.
The chloroform solution was then washed with water (5 ml)
and dried over MgSO4, and toluene (1.0 mmol) was added as
internal standard for GC analysis. After GC analysis, the
solvent was removed under vacuum, and the crude product
was subjected to silica gel column chromatography using
CHCl3–CH3OH (97:5) as eluent to afford the pure product.
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ACKNOWLEDGEMENT
Bakherad, M.; Keivanloo, A.; Bahramian, B.; Rajaie, M. A copper-
and solvent-free coupling of acid chlorides with terminal alkynes
catalyzed by a polystyrene-supported palladium(0) complex under
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The authors are grateful to the Research Council of
Shahrood University of Technology for financial support of
this work.
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