The first heterogeneous Sonogashira coupling reaction of aryl halides with terminal alkynes catalyzed by diatomite-supported palladium(II) salophen complex

Article abstract of DOI:10.1002/aoc.1778

We report here our observation that, using appropriate reaction conditions, the Sonogashira reaction can be performed without the need for copper catalyst and solvent. Our approach involves the use of diatomite-supported palladium(II) salophen complex as a catalyst and triethylamine as a base. The methodology works, to differing extents, for aryl iodides and bromides. This heterogeneous catalyst can be reused at least five times without any decrease in activity.

Full text of DOI:10.1002/aoc.1778

Full Paper
Received: 20 September 2010
Revised: 11 December 2010
Accepted: 17 January 2011
Published online in Wiley Online Library: 14 April 2011
(wileyonlinelibrary.com) DOI 10.1002/aoc.1778
The first heterogeneous Sonogashira coupling
reaction of aryl halides with terminal alkynes
catalyzed by diatomite-supported
palladium(II) salophen complex
∗
Bahram Bahramian, Mohammad Bakherad , Ali Keivanloo, Zohre Bakherad
and Behzad Karrabi
We report here our observation that, using appropriate reaction conditions, the Sonogashirareactioncan beperformedwithout
the need for copper catalyst and solvent. Our approach involves the use of diatomite-supported palladium(II) salophen complex
as a catalyst and triethylamine as a base. The methodology works, to differing extents, for aryl iodides and bromides. This
Lh te dt .e rogeneous catalyst can be reused at least five times without any decrease in activity. Copyright ꢀc 2011 John Wiley & Sons,
Keywords: copper- and solvent-free; supported catalyst; Sonogashira coupling; aryl halides
Introduction
diatoms.[6] Owing to the extremely porous structure, low density
and high surface area of diatomite, it is possible to use it for the
adsorptionoforganicandinorganicchemicals. 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
2
The palladium-catalyzed sp –sp Sonogashira coupling reaction of
terminal alkynes with aryl halides
[
1–5]
is one of the most valuable
methods for the synthesis of arylated alkynes. A number of studies
have been reported on homogeneously catalyzed reactions.[
In Sonogashira coupling reaction, copper salts usually play an
important role in assisting the oxidative addition of acetylene to
palladium metal. This method has drawbacks, though, including
wasteproductionandthenecessityofseparationafterthereaction.
Recently, some successful examples of copper-free homogeneous
Sonogashira coupling reactions have been reported for the
6]
[24–27]
adsorbance ability and excellent thermal resistance.
As part of our continuing interest in heterogeneous palladium-
[28,29]
catalyzed Sonogashira coupling reactions,
we report herein
ourresultsdemonstratingthattheSonogashiracouplingofvarious
aryl halides with terminal acetylenes proceeds in the presence
of a diatomite-supported palladium(II) salophen complex under
copper-and solvent-free conditions.
[
7–11]
reduction of the drawbacks for the use of copper salts.
Two complications with the Sonogashira couplings is that the
reaction needs degassed solvents, and that it has to be carried out
[
12,13]
under an inert atmosphere.
This is particularly inconvenient
Results and Discussion
when the reactions are carried out in multiple vessels for library
generation. Therefore, the development of a convenient method
is an important objective in this effort. From the standpoint
of environmentally benign organic synthesis, the development
of highly active and easily reusable immobilized catalysts and
a solvent-free medium are of great interest to chemists.[
Moreover, there have been many efforts on the development
of copper-free methodologies.
palladium catalysts have successfully been used for the Heck,
Suzuki and Sonogashira reactions, among others.
Zhang and co-workers
The synthesis of the diatomite-supported Pd(II) salophen complex
was carried out using a slight modification of the procedure
previouslyreportedforthesynthesisofdiatomite-supportedMn(II)
[30]
salophen. Specifically, 2.0 g of diatomite was added to 100 ml
14,15]
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, filtered and
washed with ethanol. The catalyst was then obtained by drying
[
16–21]
So far, polymer-supported
[
22]
Recently,
[
23]
reported that the Pd nanoparticles
◦
the solid under vacuum at 100 C for 12 h (Scheme 1).
immobilized on natural diatomite are highly active for Heck
and Suzuki reactions and can be recovered and reused many
times. However, to the best of our knowledge, there has been
no general study of the Sonogashira coupling reaction catalyzed
by diatomite-supported palladium complex catalyst described to
date.
A new heterogeneous catalyst has been prepared by salophen
ligand diffusion in Pd(II)-modified diatomite. The palladium
∗
Correspondence to: Mohammad Bakherad, School of Chemistry, Shahrood
University of Technology, Shahrood Iran. E-mail: m.bakherad@yahoo.com
Diatomite (SiO2 · nH2O) or diatomaceous earth is a siliceous
rock made up largely from the skeletons of aquatic plants called
School of Chemistry, Shahrood University of Technology, Shahrood Iran
Appl. Organometal. Chem. 2011, 25, 420–423
Copyright ꢀc 2011 John Wiley & Sons, Ltd.

Sonogashira coupling reaction of aryl halides with terminal alkynes
PdCl (PhCN)2
2
N
O
N
O
N
N
EtOH, diatomite, Reflux
Pd
OH
HO
Scheme 1. Preparation of the diatomite-supported Pd(II) salophen complex.
Table 1. Copper-free Sonogashira reaction of phenylacetylene with
Table 2. Copper-free Sonogashira reaction of phenylacetylene with
a
iodobenzenea
iodobenzene
b
b
Entry
Solvent
Base
Yield (%)
Entry
Base
Catalyst (mol%)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
THF
Et3N
86
42
80
70
84
77
57
64
69
61
83
78
70
68
85
76
68
90
55
65
1
DIEA
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.2
0.1
5
5
94
97
93
92
89
88
85
87
83
92
90
78
97
94
92
DIEAc
2
Et3N
Pyrrolidine
Pyridine
Piperidine
Et3N
3
Pyrrolidine
Pyridine
Et2NH
BuNH2
PrNH2
EtNH2
5
4
5
5
5
6
5
Diea
7
5
Pyrrolidine
Pyridine
Piperidine
Et3N
8
5
9
Ethanolamine
KOH
5
10
11
12
13
14
15
16
17
18
19
20
10
11
12
13
14
15
5
K2CO3
Cs2CO3
Et3N
5
THF
DIEA
5
THF
Pyrrolidine
Pyridine
Piperidine
Et3N
3
THF
Et3N
10
15
THF
Et3N
NMP
a
Reaction conditions: phenylacetylene (1.5 mmol), iodobenzene
1.0 mmol), base (2.0 mmol), room temperature, aerobic conditions.
NMP
DIEA
(
NMP
Pyrrolidine
Pyridine
Piperidine
b GC yield.
NMP
NMP
a
Reaction conditions: phenylacetylene (1.5 mmol), iodobenzene
The coupling of phenyacetylene with iodobenzene was initially
studied as a model reaction. The reaction conditions were
systematically optimized, and the results are presented in Table 1.
It was found that the best system for the reaction was NMP
in combination with pyrrolidine, which delivered a 90% yield
of diphenylacetylene within 5 h when 0.3 mol% of diatomite-
supportedPd(II)salophencomplexwasused(Table 1,entry18).Itis
interestingthatthehighestyieldofproductwasobtainedwhenthe
reaction was performed under solvent-free conditions (Table 2).
As shown in this table, when the reaction of phenylacetylene with
(
1.0 mmol), diatomite–Pd(II) salophen (0.3 mol%), base (2.0 mmol),
solvent (2 ml), 5 h, room temperature, aerobic conditions.
b
GC yield.
Diisopropylethylamine.
c
content of diatomite-supported Pd(II) salophen, which was
determined by inductively coupled plasma (ICP), was obtained to
be 3.38%. A comparison of the FT-IR spectra of the encapsulated
complex with that of the ‘free complex’ indicates the presence of
the complex inside the diatomite cavities and pores.
iodobenzene was performed with Et N as base, an excellent 97%
3
yield of the product was obtained (entry 2). Increasing the amount
The IR spectra of diatomite show major adsorption bands at
436, 1637, 1087, 796, 625, 526 and 471 cm . The band at
of palladium catalyst shortened the reaction time but did not
increase the yield of diphenylacetylene (entry 13). A low palladium
concentration led to a long reaction time (entry 14).
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 of
different alkynes 1 with aryl iodides and bromides 2 containing
electron-withdrawing or donating substituents. The results are
tabulated in Table 3.
−
1
3
3
−
1
436 cm is due to the free silanol group (Si–O–H), the band
−
1
at 1637 cm represents H–O–H bending vibration of water,
the band at 1087 cm reflects the siloxane (–Si–O–Si–) group
stretching and the bands at 526 and 471 cm are attributed to
the Si–O–Si bending vibration.
−
1
−
1
The IR spectra of [Pd(salophen)]-diatomite show major bands
−
1
at 3050 (Carom–H), 1610 (C N), 1570, 1530, 1100 and 790 cm
,
which are absent in the diatomite. The IR spectra of complex
show a shift in the υC N to a lower frequency compared with
free ligand because of coordination of azomethine nitrogen to
the palladium, which indicates the formation of Pd(II) salophen
complex.
The coupling of phenylacetylene with iodobenzene took
place smoothly at room temperature in the presence of Et3N
(2 mmol) and 0.3 mol% palladium of the diatomite-supported
Pd(II) salophen complex to give a good yield of diphenylacetylene
(entry 1).
Appl. Organometal. Chem. 2011, 25, 420–423
Copyright ꢀc 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

B. Bahramian et al.
Table 3. Copper- and solvent-free Sonogashira reactions of terminal alkynes with aryl halidesa
diatomit-supported
Pd(II)salophen complex
R
+
X
R
Et N, 5h, r. t.
3
Y
Y
1
2
3
Entry
R
X
Y
Yield (%)b
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
I
I
H
97 (96)c
98
94
93
96
95
98
92
94
96
94
93
95
95
98
98
97
96
74
82
97
94
84
96
98
87
4-NO2
4-Cl
I
I
4-Br
I
4-MeO
H
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
CH2OH
CH2OH
CH2OH
Ph
I
I
4-NO2
4-Cl
I
I
4-Br
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
I
4-MeO
H
I
I
4-MeO
4-MeCO
H
I
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Ph
4-NO2
3-NO2
4-CN
4-F
Ph
Ph
Ph
Ph
4-MeO
H
n-C4H9
n-C4H9
n-C4H9
n-C4H9
CH2OH
CH2OH
CH2OH
4-NO2
4-F
4-MeO
H
4-NO2
4-MeO
a
b
c
Reaction conditions: 1 (1.5 mmol), 2 (1.0 mmol), [diatomite–Pd(II) salophen] (0.003 mmol), Et3N (2 mmol), 5 h, room temperature, aerobic conditions.
GC yield.
Third cycle.
The Sonogashira reactions of electron-rich aryl iodides with
showed lower reactivity under similar conditions (entries 19, 23
and 26). The feasibility of recycling the diatomite-supported Pd(II)
salophen complex was also examined. We presented the experi-
mental results on the recycling of the supported Pd on a model
reaction of phenylacetylene with iodobenzene. After each round,
thesupportedcatalystwasrecoveredbysimplecentrifugationand
used directly for the next round of the reaction without further
manipulation. The diatomite-supported Pd(II) salophen complex
exhibited only a marginal loss in activity to achieve similar results
after the third cycle (Table 3, entry 1).
terminal alkynes proceeded smoothly to give the corresponding
coupling products in high yields (entries 5, 10 and 12). Unsur-
prisingly, p-nitroiodobenzene was found to be the most reactive
amongstthearyliodidesstudied(entries2and7). Asexpected, aryl
iodides with electron-withdrawing groups reacted faster than aryl
iodides possessing electron-donating groups to give the desired
products in high yields.
To extend the scope of our work, we next investigated
the coupling of various aryl bromides with terminal alkynes.
As expected, aryl iodides were more reactive than aryl bro-
mides. However, as shown in Table 3, high catalytic activity
was observed in the coupling of inactivated aryl bromides
such as p-nitrobromobenzene (entries 15, 21 and 25) as well
as activated p-nitroiodobenzene (entries 2 and 7). Moreover,
m-nitroiodobenzene, p-bromobenzonitrile and p-fluorobromo-
benzene, havingelectron-deficientaromaticrings, alsounderwent
the Sonogashira coupling with terminal alkynes under similar con-
ditions to afford the corresponding products in excellent yields
Conclusion
In summary, we presented a new supported catalyst in which
the Pd(II) salophen complex was immobilized on widespread
natural diatomite by a simple procedure. The catalyst showed
high activity for copper-free Sonogashira coupling reaction of
alkynes with halobenzenes, and could be recovered easily and
reused many times. This novel supported catalyst is air-stable, and
(
entries 16, 17, 18 and 22), although the electron-rich bromoarene
wileyonlinelibrary.com/journal/aoc
Copyright ꢀc 2011 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2011, 25, 420–423

Sonogashira coupling reaction of aryl halides with terminal alkynes
all the reactions can be conducted in air. All these virtues indicate References
that the diatomite-supported catalyst has potential applications.
[
[
[
1] A. F. Littke, G. C. Fu, Angew. Chem. Int. Ed. 2002, 41, 4176.
2] E. Negishi, L. Anastasia, Chem. Rev. 2003, 103, 1979.
3] K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew. Chem. Int. Ed. 2005, 44,
4442.
Experimental Section
[
4] H. Doucet, J.-C. Hierso, Angew. Chem. Int. Ed. 2007, 46, 834.
Allmaterialswerecommercialreagentgrade.Alkyneandarylhalide
compounds were obtained from Merck or Fluka. Diatomite sample
was supplied as a natural resource from Tabriz, Iran.
[5] C. N a´ jera, R. Chinchilla, Chem. Rev. 2007, 107, 874.
[
[
[
[
6] J. C. Moore, Acc. Chem. Res. 1997, 30, 402.
7] M. Alami, F. Ferri, G. Linstrucmelle, Tetrahedron Lett. 1993, 34, 6403.
8] N. E. Leadbeater, B. J. Tominack, Tetrahedron Lett. 2003, 44, 8653.
9] X. Fu, S. Zhang, J. Yin, D. P. Schumacher, Tetrahedron Lett. 2002, 43,
6
673.
Typical Procedure for the Preparation of Diatomite-supported
Pd(II) Salophen Complex
[
[
10] J.-F. Nguefaek, V. Bolitt, D. Sinou, Tetrahedron Lett. 1996, 37, 5527.
11] D. A. Alonso, C. N a´ jera, M. C. Pacheco, Tetrahedron Lett. 2002, 43,
9
365.
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. Then 10.0 mmol (0.318 g) of
salophenwasaddedtothesuspension,andthemixturewasfurther
refluxed for 12 h. The resulting product was filtered, washed with
[
[
12] V. P. M. B o¨ hm, W. A. Herrmann, Eur. J. Org. Chem. 2000, 22, 3679.
13] T. Hundertmark, A. F. Littke, S. L. Buchwald, G. C. Fu, Org. Lett. 2000,
2, 1729.
[14] N. E. Leadbeater, Chem. Commun. 2005, 2881.
15] C. J. Li, Chem. Rev. 2005, 105, 3095.
[
[
16] M. Bandini,R. Luque,V. Budarin,D. J. Macquarrie,Tetrahedron2005,
61, 9860.
◦
ethanol, and dried at 100 C for 12 h to give diatomite-supported
[
17] B. M. Choudary, S. Madhi, N. S. Chowdari, M. L. Kantam, B. Sreedhar,
Pd(II) salophen complex.
J. Am. Chem. Soc. 2002, 124, 14127.
18] L. Djakovitch, P. Rollet, Tetrahedron Lett. 2004, 45, 1367.
19] L. Djakovitch, P. Rollet, Adv. Synth. Catal. 2004, 346, 1782.
[
[
General Procedure for the Sonogashira Reaction Catalyzed
by Diatomite-supported Pd(II) Salophen Complex
[20] P. Rollet, W. Kleist, V. Dufaud, L. Djakovitch, J. Mol. Catal. A 2005,
241, 39.
[
21] M. Cai, Q. Xu, J. Sha, J. Mol. Catal. A 2007, 272, 293.
An aryl halide (1.0 mmol) and a terminal alkyne (1.5 mmol)
was added to a mixture of diatomite-supported Pd(II) salophen
complex (0.3 mol%) and base (2 mmol) in a glass flask under
vigorous stirring. The mixture was stirred at room temperature for
[22] L. Yin, J. Liebscher, Chem. Rev. 2007, 107, 133.
[23] Z. Zhang, Z. Wang, J. Org. Chem. 2006, 71, 7485.
[24] S. Akyuz, T. Akyuz, N. M. Ozer, J. Mol. Struct. 2001, 565, 493.
[
25] E. Gal a´ n, I. Gonz a´ lez, E. Mayoral, A. Miras, Appl. Clay Sci. 1993, 8, 1.
[26] B. Erdogan, S. Demirci, Y. Akay, Appl. Clay Sci. 1996, 11, 55.
[27] P. V. Vasconcelos, J. A. Labrincha, J. M. F. Ferreira, J. Eur. Ceram. Soc.
2000, 20, 201.
5
h under aerobic conditions. Upon completion of the reaction,
the reaction mixture was dissolved in chloroform (10 ml). The
palladium catalyst was recovered by simple centrifugation, and
reused in the next run. The chloroform solution was washed with
water (10 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, leaving the crude product.
[
[
28] M. Bakherad, A. Keivanloo, B. Bahramian, S. Mihanparast, Tetrahe-
dron Lett. 2009, 50, 6418.
29] M. Bakherad,A. Keivanloo,B. Bahramian,M. Rajaie,TetrahedronLett.
2
010, 51, 33.
[30] B. Bahramian,F. D. Ardejani,V. Mirkhani,K. Badii,Appl.Catal.A2008,
345, 97.
Acknowledgment
We are grateful to the Research Council of Shahrood University of
Technology for the financial support of this work.
Appl. Organometal. Chem. 2011, 25, 420–423
Copyright ꢀc 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc