Silica-supported zinc bromide (ZnBr2/SiO2): A highly efficient heterogeneous catalyst for coupling acid chlorides with terminal alkynes

Article abstract of DOI:10.1016/j.tetlet.2011.01.101

Silica-supported zinc bromide (ZnBr₂/SiO₂) is an efficient heterogeneous catalyst for the rapid synthesis of ynones by cross-coupling of acid chlorides with terminal alkynes in good to excellent yields under solvent-free conditions a

Full text of DOI:10.1016/j.tetlet.2011.01.101

Tetrahedron Letters 52 (2011) 1498–1502
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Tetrahedron Letters
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Silica-supported zinc bromide (ZnBr2/SiO2): a highly efficient heterogeneous
catalyst for coupling acid chlorides with terminal alkynes
⇑
Ali Keivanloo , Mohammad Bakherad, Bahram Bahramian, Samaneh Baratnia
School of Chemistry, Shahrood University of Technology, Shahrood, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Silica-supported zinc bromide (ZnBr2/SiO2) is an efficient heterogeneous catalyst for the rapid synthesis
of ynones by cross-coupling of acid chlorides with terminal alkynes in good to excellent yields under sol-
vent-free conditions at room temperature.
Received 1 October 2010
Revised 19 January 2011
Accepted 25 January 2011
Available online 1 February 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Ynone
Supported catalyst
Heterogeneous
Terminal alkyne
1. Introduction
O
O
ZnBr2 / SiO2
neat, DIPEA
R2
CH
R1
R1
Ynones are compounds of considerable synthetic interest be-
cause of their occurrence in a wide variety of biologically active
molecules and as key synthetic intermediates.1 Their role as syn-
thetic intermediates is important for the preparation of numerous
biologically active heterocyclic compounds.2
Cl
+
R2
3
2
1
Scheme 1. Silica-supported zinc bromide coupling reaction of acyl chlorides with
The preparation of ynones typically involves the reaction of alky-
nyl organometallic reagents of silver,3 copper,4 sodium,5 lithium,6
cadmium,7 zinc,8 silicon,9 or tin10 with acid chlorides. The combina-
tion of copper(I) salts with a tertiary amine is also widely used.11
However, these methods require anhydrous solvents, inert atmo-
spheres, and the use of toxic triethylamine as a solvent or base.11a,1c
Mostofthereported methodshavedisadvantagessuch aslow yields,
use toxic or expensive reagents, and require long reaction times.
Heterogeneous catalysts have gained significant attraction due
to economic and environmental considerations. The catalysts used
are generally inexpensive and readily available. They can be han-
dled conveniently and removed from the reaction mixture, thus
making experimental procedures simple.
As part of our continuing interest in palladium-catalyzed car-
bon–carbon cross-coupling reactions, we recently reported the
use of heterogeneous and homogeneous Pd-catalysts for coupling
reactions at ambient temperature under copper-free conditions.12
We have extended our studies to the synthesis of ynones by
cross-coupling acid chlorides with terminal alkynes in the pres-
terminal alkynes.
ence of silica-supported zinc bromide (ZnBr2/SiO2) under solvent-
free conditions (Scheme 1).
Previously, Lee et al. reported the alkynylation of N-tosylimines
and quinolinium salts with aryl acetylenes promoted by ZnBr2 and
N,N-diisopropylethylamine (DIPEA, Hünig’s base) in acetonitrile.13
They have also reported the coupling of acid chlorides with termi-
nal alkynes employing ZnBr2 as the catalyst, but utilized an excess
of the catalyst (1.2 equiv) in the presence of an organic solvent and
a base.14
Initially, we screened a variety of combinations of solvents and
bases as shown in Table 1 using p-chlorobenzoyl chloride (1b)
(R1 = 4-Cl–C6H4–) and phenylacetylene (2a) (R2 = C6H5–) as repre-
sentative examples. N,N-Dimethylformamide and acetonitrile
proved to be good solvents, and among the bases tested, pyridine
was the most efficient for this coupling reaction (entries 3 and 8).
To our surprise, the highest yield of product was obtained when
the reaction was performed under solvent-free conditions. As
shown in Table 1, when the reaction was performed with DIPEA
as base, an excellent yield of 98% of the expected product was ob-
tained (entry 11). Consequently, all subsequent reactions were per-
formed neat under anhydrous conditions.
⇑
Corresponding author. Fax: +98 2733395441.
E-mail addresses: akeivanloo@yahoo.com, keivanloo@shahroodut.ac.ir (A. Kei-
vanloo).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.01.101

A. Keivanloo et al. / Tetrahedron Letters 52 (2011) 1498–1502
1499
Table 1
that 0.1 g of ZnBr2/SiO2 (0.12 mmol ZnBr2) and 120 min (entry 5)
were the optimum. Increasing the amount of catalyst shortened
the reaction time but did not increase the yield (entry 4). A low
concentration of zinc bromide resulted in a decreased yield (entry
7). Increasing the reaction time (entry 8) did not increase the yield
of product further.
To examine the scope of this coupling reaction, various benzoyl
chlorides 1 containing either electron-withdrawing or electron-
donating groups were coupled with different terminal alkynes 2
(Table 3). The results show that this reaction is equally facile with
both electron-donating and electron-withdrawing substituents
present on the aroyl chloride and affords excellent yields of the
corresponding ynones.
In summary, we have developed an efficient method for the
synthesis of ynones from the reaction of acid chlorides with 1-al-
kynes in the presence of DIPEA using ZnBr2/SiO2 as catalyst under
solvent-free conditions. We believe that the present procedure
provides a useful method for the synthesis of ynones which are
key intermediates for the preparation of several important biolog-
ically active molecules. The simple procedure, short reaction time
and excellent isolated yields make this method well-suited for
the generation of a combinatorial library of ynones.
Silica-supported zinc bromide coupling reaction of p-chlorobenzoyl chloride (1b)
with phenylacetylene (2a) in the presence of different bases and solventsa
Entry
Solvent
Base
Yieldb (%)
1
2
3
4
5
6
7
8
CH3CN
CH3CN
CH3CN
THF
THF
DMF
DIPEAc
Et3N
Pyridine
DIPEA
Et3N
DIPEA
Et3N
Pyridine
DIPEA
Et3N
56
90
92
35
40
73
69
89
83
80
98
89
93
DMF
DMF
9
1,4-Dioxane
1,4-Dioxane
10
11
12
13
d
—
—
—
DIPEA
Et3N
Pyridine
d
d
a
Reaction conditions: p-chlorobenzoyl chloride (1.2 mmol), phenylacetylene
(1.0 mmol), base (1.2 mmol), solvent (1 mL), ZnBr2/SiO2 (0.1 g), rt.
b
GC yield.
Diisopropylethylamine.
Solvent-free.
c
d
Table 2
Solvent-free coupling reaction of p-chlorobenzoyl chloride with phenylacetylene (2a)
2. Preparation of silica-supported zinc bromide
in the presence of varying amounts of catalyst and over different reaction timesa
Entry
ZnBr2 (mmol)
Time (min)
Yieldb (%)
Silica gel (Wakogel C-100, 3.65 g) was added to a solution of
ZnBr2 (6 mmol, 1.35 g) in MeOH (20 ml), and the mixture was
heated at reflux for 1 h. The solvent was removed on a rotary evap-
orator and the product was dried under vacuum at 150 °C for 10 h.
Inductively coupled plasma atomic absorption spectrometry (ICP)
indicated that 1.2 mmol of ZnBr2 was supported on 1 g of ZnBr2/
SiO2.
1
2
3
4
5
6
7
8
0.24
0.24
0.24
0.24
0.12
0.06
0.03
0.12
30
60
90
100
120
120
120
150
38
56
91
98
98
65
30
98
a
Reaction conditions: p-chlorobenzoyl chloride (1.2 mmol), phenylacetylene
3. General procedure for the synthesis of ynones
(1.0 mmol), DIPEA (1.2 mmol), catalyst, rt.
b
GC yield.
A test-tube was charged with the acyl chloride (1.2 mmol), a
terminal alkyne (1.0 mmol), ZnBr2/SiO2 (0.1 g, 0.12 mmol), and DI-
PEA (1.2 mmol). The mixture was stirred at room temperature for
2 h under anhydrous conditions. Upon completion of the reaction
The conditions with respect to the amount of catalyst and the
reaction times, were optimized as shown in Table 2. It was found
Table 3
Solvent-free coupling reactions of various acyl chlorides with terminal alkynesa
Entry
Benzoyl chloride
Alkyne
Product
Yieldb (%)
O
CH
O
Cl
1
95 (90)
2a
1a
3a
O
O
H
C
CH
13
6
2b
2
3
1a
1a
82 (78)
C H
6
13
3b
H9C4
CH
2c
80 (74)
C H
4
9
3c
(continued on next page)

1500
A. Keivanloo et al. / Tetrahedron Letters 52 (2011) 1498–1502
Table 3 (continued)
Entry
Benzoyl chloride
Alkyne
Product
Yieldb (%)
98 (95)
O
O
O
Cl
4
5
6
2a
Cl
Cl
1b
3d
1b
2c
90 (85)
C H
4
9
Cl
3e
O
O
O
O N
2
O N
2
Cl
Cl
2a
89 (86)
1c
3f
O
7
2a
99 (94)
O N
2
O N
2
1d
1e
3g
O
O
Cl
8
2a
90 (86)
CH O
3
CH O
3
3h
O
9
1e
2c
2a
75 (71)
C H
4
9
CH O
3
3i
O
O
Cl
10
70 (64)
CH
O
CH
O
3
3
1f
3j
Cl
11
2a
91 (87)
I
I
1g
3k
O
O
Cl
12
2a
87 (82)
H C
3
H C
3
1h
3l

A. Keivanloo et al. / Tetrahedron Letters 52 (2011) 1498–1502
1501
Table 3 (continued)
Entry
Benzoyl chloride
Alkyne
Product
Yieldb (%)
O
13
1h
2b
75 (68)
C H
6
13
H C
3
3m
3n
3o
O
O
Cl
Cl
14
2a
77 (74)
Br
Cl
Br
Cl
1i
O
O
15
2a
92 (89)
Cl
Cl
1k
O
O
Cl
16
2a
84 (81)
1l
3p
O
O
S
S
Cl
17
2a
92 (86)
1m
3q
a
Reaction conditions: 1 (1.2 mmol), 2 (1.0 mmol), DIPEA (1.2 mmol), catalyst (0.12 mmol), rt.
GC yield. Isolated yields in parentheses.
b
(monitored by TLC), the mixture was extracted with EtOAc
(125 MHz, CDCl3): d 86.74, 93.79, 119.96, 128.90, 129.68, 131.02,
131.07, 132.08, 133.25, 135.81, 176.85; Anal. Calcd for C15H9BrO:
C, 63.18; H, 3.18; found: C, 63.20; H, 3.15.
(3 Â 5 mL). The organic layers were combined and washed with
H2O (2 Â 5 mL) to remove the amine hydrochloride formed during
the reaction. The organic layer was separated, dried over anhy-
drous MgSO4, filtered, and concentrated under vacuum to give
the product which was further purified by column chromatogra-
phy using hexane/EtOAc (20:1) as eluent.
3.3. 1-(2,4-Dichlorophenyl)-3-phenylprop-2-yn-1-one (3o)
IR (KBr): 2200, 1663; 1H NMR (500 MHz, CDCl3): d 7.15–7.58
(m, 7H), 8.2 (d, J = 8.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): d
88.2, 92.5, 120.2, 128.9, 130.8, 131.2, 133.1, 135.4, 137.8, 138.2,
139.4, 143.2, 177.5; Anal. Calcd for C15H8Cl2O: C, 65.48; H, 2.93;
found: C, 65.45; H, 2.91.
Compounds 3a,15a 3b,15b 3c,15b 3d,15a 3e,12c 3f,15c 3g,15c 3h,15c
3i,15b 3j,15b 3l,15b 3m,15b 3p15c and 3q15a are known. Characteriza-
tion data for ynones 3k, 3n, and 3o are given below.
3.1. 1-(2-Iodophenyl)-3-phenylprop-2-yn-1-one (3k)
Acknowledgment
IR (KBr): 2198, 1651; 1H NMR (500 MHz, CDCl3): d 7.10–7.52
(m, 7H), 7.70–8.10 (m, 2H); 13C NMR (125 MHz, CDCl3): d 87.2,
91.4, 119.9, 127.7, 128.8, 130.3, 130.5, 130.7, 132.4, 133.2, 135.5,
144.4, 178.2; Anal. Calcd for C15H9IO: C, 54.24; H, 2.73; found: C,
54.21; H, 2.82.
The authors thank the Research Council of Shahrood University
of Technology for the support of this work.
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