Calcium carbide as a cost-effective starting material for symmetrical diarylethynes via Pd-catalyzed coupling reaction

Article abstract of DOI:10.1016/j.tet.2011.08.042

A convenient and cost-effective synthetic method for symmetrical diarylethynes from inexpensive calcium carbide and aryl iodide has been developed. The reaction not only proceeds with high yield and selectivity but also tolerates a wide range of functional groups. Application of this reaction has enabled the synthesis of highly functionalized oligo (phenyleneethynylenes) to be accomplished.

Full text of DOI:10.1016/j.tet.2011.08.042

Tetrahedron 67 (2011) 8177e8182
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Calcium carbide as a cost-effective starting material for symmetrical diarylethynes
via Pd-catalyzed coupling reaction
Padon Chuentragool a, Kunnigar Vongnam b, Paitoon Rashatasakhon a, Mongkol Sukwattanasinitt a,
,
Sumrit Wacharasindhu a
*
a Center for Petroleum, Petrochemicals, and Advanced Materials, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
b Program of Petrochemical and Polymer Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 April 2011
Received in revised form 1 August 2011
Accepted 15 August 2011
Available online 22 August 2011
A convenient and cost-effective synthetic method for symmetrical diarylethynes from inexpensive cal-
cium carbide and aryl iodide has been developed. The reaction not only proceeds with high yield and
selectivity but also tolerates a wide range of functional groups. Application of this reaction has enabled
the synthesis of highly functionalized oligo (phenyleneethynylenes) to be accomplished.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Calcium carbide
Diarylethyne
Sonogashira reaction
Phenyleneethynylene
Palladium coupling reaction
1. Introduction
Pd-catalyzed coupling reaction was pioneered by Zhang29 using
aryl bromides for preparation of symmetrical diarylethynes. Even
Over the past two decades, Pd-catalyzed cross-coupling re-
actions, such as Heck, Suzuki, Nigishi, Stille, and Sonogashira re-
actions have been the most powerful tools for CeC bond
construction.1e7 Among these, the Sonogashira cross-coupling re-
action is the most efficient method to connect sp-C to sp2-C in the
synthesis of diarylalkynes and areneethynylene polymers due to
the simplicity of the reaction process.8e18 These compounds have
caught much attention recently in the fields of bioactive com-
pounds and functional materials.19e22 Historically, the Sonogashira
reaction utilized terminal acetylene, usually obtained from pro-
tected acetylene, as an sp-C source, and later, acetylene gas has also
been used (Scheme 1).8e18,23e25 Acetylene gas is appreciably more
economical than the terminal acetylenes for the synthesis of
symmetrical diarylethyne that can be accomplished within one
step. Due to complicated handling and close attention required for
an application of highly flammable acetylene gas, the three-step
synthesis of diarylethynes from terminal acetylene is currently
a more favorable route. Recently, a number of reports demonstrated
the use of inexpensive and readily available calcium carbide, as the
acetylene surrogate in the preparation of carbon nanotubes,26 poly-
ynes,27 and aryltriazoles.28 The utilization of calcium carbide for
though it was the first report on the use of calcium carbide for the
synthesis of diarylalkynes, a non-commercially available amino
phosphine ligand and elevated reaction temperature were required
to obtain reasonable yields of the desired products. We found that
this inspiring work worth further exploring as a general and eco-
nomical synthetic approach for symmetrical diarylethynes. Herein,
we report a convenient synthetic method for symmetrical diary-
lethynes from calcium carbide and aryl iodides at room tempera-
ture using commercially available and inexpensive reagents
including the catalyst and base. The reaction also displayed a wide
range of functional group compatibility.1
Scheme 1. Typical methods for the synthesis of diarlyethynes.
* Corresponding author. Tel.: þ662 218 7634; fax: þ662 218 7598; e-mail ad-
dress: sumrit.w@chula.ac.th (S. Wacharasindhu).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.042

8178
P. Chuentragool et al. / Tetrahedron 67 (2011) 8177e8182
2. Results and discussion
However, alternative copper sources, such as CuOAc and Cu(OAc)2,
could be used in this transformation (entries 5 and 6). Base screening
indicated that TEA was the most effective base in comparison with
others, although diisopropylethylamine gave satisfactory results
(entry7). When the reactionwas carried outat 60 ꢀC, 40% of1,2-di-p-
tolylethyne was isolated without the recovery of any starting ma-
terial (entry 10). Under atmospheric condition, a lower yield of the
desired product was isolated (30%, entry 11) in comparisonwith that
under inert nitrogen environment. We were pleased to realize that
the reactions went to completion with an increased amount of cat-
alyst. Most interestingly, reaction proceeded smoothly at room
temperature (Table 1, entry 12). Thus, the optimized conditions in-
volved treatment of 4-iodotoluene 1b (1 equiv), CaC2 (3 equiv),
Pd(OAc)2 (5%), PPh3 (10%), CuI (10%), and triethylamine (3 equiv) in
MeCN at room temperature under a nitrogen atmosphere. Under
these optimized conditions, the coupling product 2b was isolated in
99% yield (Table 1, entry 12). It must be noted that under these
conditions, complete conversion to 2b was observed by NMR spec-
troscopic analysis and TLC. To the best of our knowledge, formation
of diarylethynes under these efficient and mild conditions has not
been reported in the literature.12,16e18,25,29e31,38
2.1. Initial observation
Ourinitialattemptsinvolvedthetreatmentofcalciumcarbidewith
halobenzene (Br, I) or sulfonate esters (OTs, OTf), in acetonitrile at
room temperature in the presence of Pd(OAc)2 (2.5 mol %), triphe-
nylphosphine (PPh3, 5 mol %), CuI (5 mol %), and triethylamine (TEA).
The reaction of bromobenzene or triflate gave no desired product and
onlyasmallamountof startingmaterialcouldberecoveredalongwith
unidentified complex mixtures. In the case of the tosylate, only a trace
amount of the target compound diphenylethyne was isolated along
with an almost quantitative recovery of starting material. It was as-
sumed that aryl iodides would enhance the formation of the desired
product under these conditions. To our delight, switching from bro-
mide to iodide analogues, diphenylethyne 2a was obtained in 68%
yield along with recovery of iodobenzene (15%) (Scheme 2).
2.3. Substrate scope
The new method has allowed variety functional groups to be
tested. Therefore, a series of aryl iodides either commercially available
or prepared according to literature procedures were subjected to the
coupling reaction with CaC2 under the optimized reaction conditions
(Table 1, entry 12) and the results were summarized inTable 2. Thearyl
iodides bearing an electron donating group, such as methyl, naphthyl,
and, methoxy (entries 2e4) yielded the desired bisarylacetylenes in
good to excellent yields. Notably, the substituent position effect was
foundtobeminimalinourstudy, asseeninthecaseofthreeisomersof
iodotoluenes (1b, 1c, and 1d), providing the coupling products 2b, 2c,
and 2d in 99%, 99%, and 96% yields, respectively (entry 2). However, 4-
iodobenzyl alcohol (1i) and 4-iodo aniline (1j) were not suitable for
this transformation as they afforded the target compounds, 2i in only
41% yield, while complex mixtures were obtained in the case of 1j.
These results may be due to the chelation of the palladium catalyst
with the high electron density oxygen or nitrogen atoms. The yield
was significantly increased when the hydroxyl moiety in 1i was
methylated. The product 2h was isolated in much higher yield. In-
terestingly, the presence of a sulfur atom had no effect in this reaction,
as shown in the coupling reaction of 2-iodothiophene (1k). The
product 2k was produced in 99% yield. The substrates bearing
electron-withdrawing groups, such as the aldehyde, ketone, amido,
ester, and nitro moieties reacted efficiently to obtain the coupled
products in good to high yields (entries 8e11). In contrast to previous
report, ourexperimentresultedingoodyieldsofproduct2mand 2p.29
This outcome suggests that the rate determining step of this reaction
may not be the same as the reactions investigated by Zhang.29
Moreover, other leaving groups, such as bromo and tosyl as well as
trimethylsilyl protecting groups well tolerated the reaction conditions
and iodogroupwere reacted selectively, giving the desired products in
excellent yields (entries 12e14). We attributed the wide range of
functional group tolerance to the heterogeneous nature of calcium
carbideandproperconcentrationofgraduallygeneratedacetylenegas
under the reaction condition. These high functional group selectivity
and compatibility should expand the scope of this reaction in the
Scheme 2. Initial observation. All reactions were carried out with phenyl derivatives
(1 equiv), CaC2 (3 equiv), Pd(OAc)2 (2.5%), CuI (5%), PPh3 (5%), and triethylamine
(3 equiv) at rt for 10 h.
2.2. Reaction condition screening
Following this initial observation, 4-iodotoluene (1b) was se-
lected, due to a clear difference between the methyl group 1H NMR
signal of the starting material 1b and that of its product 2b, for re-
action optimization, including palladium and copper sources, bases,
temperature, and catalyst amount (Table 1). Pd(OAc)2 was found to
be the most effective palladium source for this reaction in compar-
ison with bis(triphenylphosphine)-palladium(II) dichloride and
palladium tetrakis (entries 1e3). Cleary, CuI is needed in the re-
action, and its absence resulted in a lower yield (22%, entry 4).
Table 1
Optimization of reaction conditiona
Entry
Pd/Cu source
Base
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
Pd(OAc)2/CuI
PdCl2(PPh3)2/CuI
Pd(PPh3)4/CuI
Pd(OAc)2/d
Pd(OAc)2/CuOAc
Pd(OAc)2/(CuOAc)2
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
TEA
TEA
TEA
TEA
TEA
TEA
DIPEA
K2CO3
K2CO3
TEA
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
MeOH
MeCN
MeCN
MeCN
50
24
24
22
50
50
41
0c
16
40d
30e
99f
9
10
11
12
TEA
TEA
a
synthesis of more complex
modification at the remaining reactive groups.
p-conjugated molecules with further
Unless otherwise noted, a mixture of 4-iodotoluene (1 equiv), CaC2 (3 equiv), Pd
catalyst (2.5%), PPh3 (5%), Cu catalyst (5%), and base (3 equiv) was stirred at room
temperature for 10 h.
b
Isolated yield.
4-Iodotoluene (90%) was recovered.
Heated at 60 ꢀC.
Reaction was carried out under air.
Pd(OAc)2 (5%), 10% CuI, and 10% of PPh3 were used.
2.4. Synthesis of oligo (phenyleneethynylenes)
c
d
e
The success of this Pd-catalyzed reaction turned our attention to
the synthesis of oligo-(aryleneethynylenes). Such compounds
f

P. Chuentragool et al. / Tetrahedron 67 (2011) 8177e8182
8179
Table 2
Substrate compatibilitya
Entry
1
Aryl iodide
Product
Yieldb
96%
Entry
8
Aryl iodide
Product
Yieldb
2l
2m
99%
87%
2a
1a
R = Me ; 1l
R = H ; 1m
2b
2c
2d
99%
99%
96%
2
9
2n
94%
p;1b, m;1c, o;1d
1n
3
4
2e
96%
10
11
2o
2p
74%
96%
1o
1e
2f
2g
96%
80%c
R = Me; 1f
R = H ; 1g
1p
2h
2i
99%
5
6
12
2q
97%
41%c
1q
R = Me; 1h
R = H ; 1i
2j
Complex mixture
13
14
2r
2s
97%
99%
1r
1j
7
2k
99%
1s
1k
a
General conditions: a mixture of aryl iodides (1 equiv), CaC2 (3 equiv), Pd(OAc)2 (5%), PPh3 (10%), CuI (10%), and TEA (3 equiv) was stirred for 12 h, and purified by filtration
through a short plug of silica gel.
b
Isolated yield.
Purified by column chromatography.
c
attracted considerable interest due to their electronic and photonic
properties, which have been applied widely in chemo- and bio-
sensors and electronic devices.32e36 Compounds 2t and 2u bearing
three phenyleneethynylene units were prepared from the corre-
sponding iodo-phenyleneethynylenes1t and 1u with calcium car-
bide under the optimized conditions in 87 and 51% yields,
respectively (Scheme 3).
2.5. Effect of water on the reaction
As mentioned above, the reactions were carried out using
undried acetonitrile as solvent, we therefore decided to investigate
the effect of water on the reaction. The coupling reaction of 4-
iodotoluene (1b) and calcium carbide were conducted in freshly
distilled acetonitrile and the targeted product 2b was isolated in
52% yield (Table 3, entry 1). Upon the addition of 1.2 or 3.6 equiv of
H2O, the reaction went completely and the coupling product was
obtained in quantitative yield (Table 3, entries 2 and 3). On the basis
of these data, water is clearly necessary for the reaction. Thus, we
hypothesized that the reaction is initiated by the hydrolysis of
calcium carbide with H2O to produce acetylene gas, which is then
COOMe
RO
I
Pd(OAc)2, CuI, PPh3
CaC2
+
TEA, MeCN, rt, 10 h, N2
OR
R = n-Bu; 1t
R = -(CH2)3OAc;
1u
Table 3
Effect of water on coupling reaction between 4-iodotoluene and calcium carbidea
RO
RO
Entry
H2O added to freshly distilled CH3CN (equiv)
Yield of 2bb (%)
MeOOC
COOMe
1
2
3
0
1.2
3.6
52
99
99
2t; 87%
2u
OR
OR
; 51%
Scheme 3. Synthesis of 2t and 2u.
a
General conditions: a mixture of aryl iodides (1 equiv), CaC2 (3 equiv), Pd(OAc)2
(5%), PPh3 (10%), CuI (10%), and TEA (3 equiv) was stirred for 10 h.
b
Isolated yield.

8180
P. Chuentragool et al. / Tetrahedron 67 (2011) 8177e8182
driven through Sonogashira coupling process to yield the diary-
lethyne and HI (Scheme 4). The use of freshly distilled acetonitrile
gave coupling product in moderate yield (52%) suggesting that H2O
may not be the only proton source for hydrolysis of calcium carbide.
In addition, HI can react with calcium carbide to generate more
acetylene gas in the coupling reaction.
4.2.1. 1,2-Diphenylethyne (2a)16,29,37. Synthesized according to
general procedure from iodobenzene (200 mg, 0.98 mmol), calcium
carbide (188.5 mg, 2.94 mmol), copper iodide (18.67 mg,
0.098 mmol), palladium(II)acetate (11.0 mg, 0.049 mmol), triphe-
nylphosphine (25.7 mg, 0.098 mmol), and triethylamine (297.6 mg,
2.94 mmol) to afford 83.9 mg (0.47 mmol, 96%) of 2a as a white
solid: 1H NMR (400 MHz, CDCl3):
d ppm 7.63e7.56 (4H, m),
7.43e7.35 (6H, m); 13C NMR (100 MHz, CDCl3):
d 131.6, 128.3, 128.2,
123.2, 89.4; IR (neat, cmꢁ1) 3065, 3027.
4.2.2. 1,2-Di-p-tolylethyne (2b)16,29. Synthesized according to gen-
eral procedure from 4-iodotoluene (200 mg, 0.917 mmol), calcium
carbide (176.4 mg, 2.75 mmol), copper iodide (17.52 mg,
0.092 mmol), palladium(II)acetate (10.3 mg, 0.046 mol), triphe-
nylphosphine (24.0 mg, 0.092 mmol), and triethylamine (278.4 mg,
2.752 mmol) to afford 94.2 mg (0.456 mmol, 99%) of 2b as a white
Scheme 4. Proposed role of H2O and HI.
solid: 1H NMR (400 MHz, CDCl3):
d
ppm 7.42 (4H, d, J¼7.8 Hz), 7.15
3. Conclusion
( 4H, d, J¼7.8 Hz), 2.37 (6H, s); 13C NMR (100 MHz, CDCl3):
d 138.1,
131.4, 129.1, 120.4, 88.9, 21.5; IR (neat, cmꢁ1) 3018, 2917, 2843.
In conclusion, we have demonstrated an efficient method for
synthesizing symmetrical diarylethynes directly from basic chem-
ical feedstock, calcium carbide, via a Pd-catalyzed coupling re-
action. The reactions were carried out under mild conditions in
undried solvent, and the product can be purified by a simple fil-
tration on a bed of silica gel. Also, inexpensive and commercially
available reagents were used in the reaction. Thus, this trans-
formation is proven to be an efficient process for the preparation of
symmetrical diarylethynes. Further studies to extend the scope of
this reaction toward the synthesis of poly-phenyleneethynelenes
and related oligomers are currently under investigation and will
be reported in due course.
4.2.3. 1,2-Di-m-tolylethyne (2c)16. Synthesized according to general
procedure from 3-iodotoluene (200 mg, 0.917 mmol), calcium
carbide (176.4 mg, 2.75 mmol), copper iodide (17.52 mg,
0.092 mmol), palladium(II)acetate (10.3 mg, 0.046 mmol), triphe-
nylphosphine (24.0 mg, 0.092 mmol), and triethylamine (278.4 mg,
2.752 mmol) to afford 93.7 mg (0.454 mmol, 99%) of 2c as a white
solid: 1H NMR (400 MHz, CDCl3):
d ppm 7.36e7.33 (4H, m), 7.23
( 2H, d, J¼7.6 Hz), 7.15 ( 2H, d, J¼7.6 Hz), 2.36 (6H, s); 13C NMR
(100 MHz, CDCl3):
d 138.0, 132.2, 129.1, 128.7, 128.2, 123.2, 89.2,
21.3; IR (neat, cmꢁ1) 3050, 2917.
4.2.4. 1,2-Di-o-tolylethyne (2d)16. Synthesized according to general
procedure from 2-iodotoluene (200 mg, 0.917 mmol), calcium car-
bide (176.4 mg, 2.75 mmol), copper iodide (17.52 mg, 0.092 mmol),
palladium(II)acetate (10.3 mg, 0.046 mmol), triphenylphosphine
(24.0 mg, 0.092 mmol), and triethylamine (278.4 mg, 2.752 mmol) to
afford 91.2 mg (0.442 mmol, 97%) of 2d as a white solid: 1H NMR
4. Experimental section
4.1. General information
Unless otherwise indicated, all starting materials were
obtained from commercial suppliers, and were used without fur-
ther purification. All solvents were used directly without drying.
Calcium carbide was grinded before use. Analytical thin-layer
chromatography (TLC) was performed on Kieselgel F254 pre-
coated plastic TLC plates from EM Science. Visualization was
performed with a 254 nm ultraviolet lamp. Silica gel column
chromatography was carried out with silica gel (60,
230e400 mesh) from ICN Silitech. The 1H and 13C NMR spectra
were recorded on a Varian or Bruker (400 MHz for 1H and
100 MHz for 13C) in CDCl3, (CD3)2SO or (CD3)2CO. 1H and 13C NMR
(400 MHz, CDCl3): d ppm 7.54e7.52 (2H, m), 7.27e7.19 (6H, m), 2.55
(6H, s); 13C NMR (100 MHz, CDCl3):
d 140.0,131.9,129.5,128.2,125.6,
123.3, 92.3, 21.0; IR (neat, cmꢁ1)3056, 3009.
4.2.5. 1,2-Di(naphthalen-1-yl)ethyne (2e)16,38. Synthesized accord-
ing to general procedure from 1-iodonaphthalene (200 mg,
0.787 mmol), calcium carbide (151.4 mg, 2.36 mmol), copper iodide
(15.0 mg, 0.079 mmol), palladium(II)acetate (8.8 mg, 0.039 mmol),
triphenylphosphine (20.6 mg, 0.079 mmol), and triethylamine
(278.5 mg, 2.752 mmol) to afford 104.5 mg (0.376 mmol, 97%) of 2e
chemical shifts were referenced to CDCl3 (
d
7.26 for 1H,
39.43 for 13C) or (CD3)2CO ( 2.09 for 1H,
d
d
77.00 for
30.60
as a white solid: 1H NMR (400 MHz, CDCl3):
d ppm 8.62 ( 2H, d,
13C), (CD3)2SO (
d
d
J¼8.0 Hz), 7.92 (6H, m), 7.68 ( 2H, t, J¼7.6 Hz), 7.59 (2H, t, J¼7.4 Hz),
for 13C). Coupling constants (J) are reported in Hertz (Hz). Splitting
patterns are designated as s (singlet), d (doublet), t (triple), q
(quartet), br s (broad singlet), m (multiplet).
7.54 (2H, t, J¼7.4 Hz); 13C NMR (100 MHz, CDCl3):
d 133.2, 130.6,
128.9, 128.4126.9, 126.5, 126.3, 125.3, 121.0, 92.4; IR (neat, cmꢁ1
3056, 3009.
)
4.2. General procedure for Pd-catalyzed coupling reaction of
calcium carbide with aryl iodides
4.2.6. 1,2-Bis(4-methoxyphenyl)ethyne (2f)16,29. Synthesized accord-
ing to general procedure from 4-iodoanisole (200 mg, 0.855 mmol),
calcium carbide (164.4 mg, 2.56 mmol), copper iodide (16.3 mg,
0.086 mmol), palladium(II)acetate (9.6 mg, 0.043 mmol), triphe-
nylphosphine (22.4 mg, 0.086 mmol), and triethylamine (278.3 mg,
2.56 mmol) to afford 98.1 mg (0.412 mmol, 97%) of 2f as a white
A 100 mL round bottom flask with a magnetic stir bar was
charged with copper iodide (0.1 equiv), palladium acetate
(0.05 equiv), and triphenylphosphine (0.1 equiv) in acetonitrile. The
solution was degassed with nitrogen for 20 min. Then, triethyl-
amine (3 equiv), aryl iodides (1 equiv), and calcium carbide
(3 equiv) were added. The mixture was stirred at room temperature
overnight under nitrogen atmosphere. The reaction mixture was
then filtrated through a short plug of silica gel and washed with
hexane. The filtrate was evaporated under vacuum to give the de-
sired compound.
solid: 1H NMR (400 MHz, CDCl3):
d
ppm 7.45 ( 4H, d, J¼8.8 Hz), 6.87
( 4H, d, J¼8.8 Hz), 3.83 (6H, s); 13C NMR (100 MHz, CDCl3):
d 159.4,
132.9, 115.7, 114.0, 87.9, 55.3; IR (neat, cmꢁ1)3000, 2968, 2832.
4.2.7. 4,40-(Ethyne-1,2-diyl)diphenol (2g)38. Synthesized according
to general procedure from 4-iodophenol (200 mg, 0.91 mmol),
calcium carbide (174.8 mg, 2.73 mmol), copper iodide (17.3 mg,

P. Chuentragool et al. / Tetrahedron 67 (2011) 8177e8182
8181
0.091 mmol), palladium(II)acetate (10.2 mg, 0.045 mmol), triphe-
nylphosphine (23.0 mg, 0.091 mmol), and triethylamine (275.9 mg,
2.73 mmol) to afford 76.4 mg (0.364 mmol, 81%) of 2g as a brown
(147.3 mg, 2.36 mmol), copper iodide (14.6 mg, 0.077 mmol), pal-
ladium(II)acetate (8.6 mg, 0.034 mmol), triphenylphosphine
(20.1 mg, 0.077 mmol), and triethylamine (232.6 mg, 2.36 mmol) to
afford 105.7 mg (0.362 mmol, 94%) of 2n as a brown solid: 1H NMR
solid: 1H NMR (400 MHz, (CD3)2CO):
d ppm 8.76 (2H, s), 7.31 ( 4H, d,
J¼8.4 Hz), 6.81 ( 4H, d, J¼8.4 Hz); 13C NMR (100 MHz, (CD3)2CO):
(400 MHz, CDCl3):
d
ppm 8.31 ( 2H, d, J¼8.2 Hz), 7.90 (2H, s), 7.50 (
d
159.4, 134.6, 117.4, 116.5, 89.4.
2H, d, J¼7.5 Hz), 7.41 ( 2H, t, J¼7.9 Hz), 7.13 ( 2H, t, J¼7.5 Hz), 2.25
(6H, s); 13C NMR (100 MHz, CDCl3):
d 168.5, 139.0, 132.0, 130.4,
4.2.8. 1,2-Bis(4-(methoxymethyl)phenyl)ethyne (2h)39. Synthesized
according to general procedure from 1-iodo-4-(methoxymethyl)
benzene (200 mg, 0.86 mmol), calcium carbide (165.0 mg,
2.57 mmol), copper iodide (16.4 mg, 0.086 mmol), palladium(II)
acetate (9.6 mg, 0.043 mmol), triphenylphosphine (22.5 mg,
0.086 mmol), and triethylamine (260.6 mg, 2.57 mmol) to afford
101.1 mg (0.428 mmol, 99%) of 2h as a white solid: 1H NMR
123.9, 120.5, 91.1, 24.8; IR (neat, cmꢁ1)3293, 2959, 2920, 1729;
HRMS (ESI) calcd for C18H16N2O2Na, 315.1104; found, 315.1107.
4.2.14. Dimethyl 4,40-(ethyne-1,2-diyl)dibenzoate (2o)16. Synthe-
sized according to general procedure from 4-iodobenzoate
(200 mg, 0.76 mmol), calcium carbide (146.8 mg, 2.29 mmol),
copper iodide (14.5 mg, 0.076 mmol), palladium(II)acetate (8.6 mg,
0.038 mmol), triphenylphosphine (20.0 mg, 0.076 mmol), and
triethylamine (230.9 mg, 2.29 mmol) to afford 83.2 mg
(0.278 mmol, 74%) of 2o as a brown solid: 1H NMR (400 MHz,
(400 MHz, CDCl3):
d
ppm 7.52 ( 4H, d, J¼7.7 Hz), 7.32 ( 4H, d,
J¼7.7 Hz), 4.47 (4H, s), 3.40 (6H, s); 13C NMR (100 MHz, CDCl3):
d
138.4, 132.5, 131.6, 127.5, 122.4, 89.2, 74.2, 58.1; IR (neat, cmꢁ1
)
3003, 2923, 2864.
CDCl3):
d
ppm 8.03 ( 4H, d, J¼8.2 Hz), 7.60 ( 4H, d, J¼8.2 Hz), 3.93
(6H, s); 13C NMR (100 MHz, CDCl3):
d 166.4, 131.6, 130.0, 129.6,
4.2.9. (4,40-(Ethyne-1,2-diyl)bis(4,1-phenylene))dimethanol
(2i)38. Synthesized according to general procedure from (4-
iodophenyl)methanol (200 mg, 0.855 mmol), calcium carbide
(164.4 mg, 2.56 mmol), copper iodide (16.3 mg, 0.086 mmol), pal-
ladium(II)acetate (9.6 mg, 0.043 mmol), triphenylphosphine
(22.4 mg, 0.086 mmol), and triethylamine (259.5 mg, 2.56 mmol)
and purified by flash chromatography to afford 41.6 mg
(0.175 mmol, 41%) of 2i as a brown solid: 1H NMR (400 MHz, CDCl3):
127.4, 91.4, 52.3; IR (neat, cmꢁ1)3012, 2959, 1711.
4.2.15. 1,2-Bis(4-nitrophenyl)ethyne (2p)41. Synthesized according
to general procedure from 4-iodonitrobenzene (200 mg,
0.80 mmol), calcium carbide (154.5 mg, 2.41 mmol), copper iodide
(15.3 mg, 0.080 mmol), palladium(II)acetate (9.0 mg, 0.040 mmol),
triphenylphosphine (21.0 mg, 0.080 mmol), and triethylamine
(243.8 mg, 2.4 mmol) to afford 102.7 mg (0.400 mmol, 95%) of 2p as
d
ppm 7.53 ( 4H, d, J¼8.4 Hz), 7.35 ( 4H, d, J¼8.4 Hz), 4.72 (4H, s),
a yellow solid: 1H NMR (400 MHz, CDCl3):
d ppm 8.26 ( 4H, d,
3.41 (1H, s); 13C NMR (100 MHz, (CD3)2SO):
127.1, 127.1, 120.9, 89.4, 62.9.
d
143.4, 132.6, 131.5,
J¼8.7 Hz), 7.72 ( 4H, d, J¼8.7 Hz); 13C NMR (100 MHz, CDCl3):
d 147.7,
132.6, 128.9, 127.7, 92.0; IR (neat, cmꢁ1)3104, 3071, 2926, 1593.
4.2.10. 1,2-Di(thiophen-2-yl)ethyne (2k)16. Synthesized according
to general procedure from 2-iodothiophene (200 mg, 0.952 mmol),
calcium carbide (183 mg, 2.86 mmol), copper iodide (18.2 mg,
0.095 mmol), palladium(II)acetate (10.7 mg, 0.048 mmol), triphe-
nylphosphine (25.0 mg, 0.095 mmol), and triethylamine (289.1 mg,
2.86 mmol) to afford 89.6 mg (0.472 mmol, 99%) of 2k as a white
4.2.16. 1,2-Bis(4-bromophenyl)ethyne (2q)16. Synthesized according
to general procedure from 1-bromo-4-iodobenzene (200 mg,
0.71 mmol), calcium carbide (136 mg, 2.12 mmol), copper iodide
(13.5 mg, 0.071 mmol), palladium(II)acetate (7.9 mg, 0.035 mmol),
triphenylphosphine (18.5 mg, 0.071 mmol), and triethylamine
(214.6 mg, 2.12 mmol) to afford 115.3 mg (0.34 mmol, 97%) of 2q as
solid: 1H NMR (400 MHz, CDCl3):
d
ppm 7.33e7.26 (4H, m),
a white solid: 1H NMR (400 MHz, CDCl3):
d ppm 7.49 (4H, d,
7.05e6.99 (2H, m); 13C NMR (100 MHz, CDCl3):
d
132.1, 127.6, 127.1,
J¼8.5 Hz), 7.38 ( 4H, d, J¼8.5 Hz); 13C NMR (100 MHz, CDCl3):
d 133.0,
122.9, 86.2; IR (neat, cmꢁ1)3101, 3080.
131.7, 122.8, 121.8, 89.4; IR (neat, cmꢁ1)3074, 3071, 2926, 1593.
4.2.11. 1,10-(4,40-(Ethyne-1,2-diyl)bis(4,1-phenylene))diethanone
(2l)16,40. Synthesized according to general procedure from 1-(4-
iodophenyl)ethanone (200 mg, 0.813 mmol), calcium carbide
(156.3 mg, 2.44 mmol), copper iodide (11.6 mg, 0.081 mmol), pal-
ladium(II)acetate (9.1 mg, 0.041 mmol), triphenylphosphine
(23.3 mg, 0.081 mmol), and triethylamine (246.8 mg, 2.44 mmol) to
afford 105 mg (0.400 mmol, 99%) of 2l as a white solid: 1H NMR
4.2.17. 1,2-Bis(4-((trimethylsilyl)ethynyl)phenyl)ethyne (2r)42. Syn-
thesized according to general procedure from ((4-iodophenyl)ethy-
nyl)trimethylsilane (200 mg, 0.667 mmol), calcium carbide
(128.2 mg, 2.00 mmol), copper iodide (12.7 mg, 0.067 mmol), palla-
dium(II)acetate (7.5 mg, 0.033 mmol), triphenylphosphine (17.5 mg,
0.067 mmol), and triethylamine (202.4 mg, 2.00 mmol) to afford
118.8 mg (0.321 mmol, 96.6%) of 2r as a yellow solid: 1H NMR
(400 MHz, CDCl3):
d
ppm 7.96 (4H, d, J¼8.3 Hz), 7.63 ( 4H, d,
(400 MHz, CDCl3):
d
ppm 7.46 (4H, s), 7.44 (4H, s), 0.26 (18H, s); 13
131.9, 131.4, 123.0, 104.5, 96.5, 91.0, ꢁ0.1.
C
J¼8.3 Hz), 2.62 (6H, s); 13C NMR (100 MHz, CDCl3):
d
197.2, 136.6,
NMR (100 MHz, CDCl3): d
131.9, 128.3, 127.5, 91.6, 26.6.
4.2.18. 4,40-(Ethyne-1,2-diyl)bis(4,1-phenylene) bis(4-methylbenze-
nesulfonate) (2s). Synthesized according to general procedure
4.2.12. 4,40-(Ethyne-1,2-diyl)dibenzaldehyde
(2m)29. Synthesized
according to general procedure from 4-iodobenzaldehyde (200 mg,
0.858 mmol), calcium carbide (165.1 mg, 2.57 mmol), copper iodide
(16.4 mg, 0.086 mmol), palladium(II)acetate (9.6 mg, 0.043 mmol),
triphenylphosphine (22.5 mg, 0.086 mmol), and triethylamine
(261.4 mg, 2.57 mmol) to afford 87.7 mg (0.372 mmol, 87%) of 2m as
from
4-iodophenyl
4-methylbenzenesulfonate
(200
mg,
0.536 mmol), calcium carbide (103 mg, 1.63 mmol), copper iodide
(10.2 mg, 0.05 mmol), palladium(II)acetate (6.0 mg, 0.027 mmol),
triphenylphosphine (14.0 mg, 0.05 mmol), and triethylamine
(162.2 mg,1.63 mmol) to afford 137.7 mg (0.266 mmol, 99.4%) of 2s as
a yellow solid: 1H NMR (400 MHz, CDCl3):
d
ppm 10.04 (1H, s), 7.90
a brown solid: 1H NMR (400 MHz, CDCl3):
d ppm 7.70 ( 4H, d,
( 2H, d, J¼8.4 Hz), 7.71 ( 2H, d, J¼8.4 Hz); 13C NMR (100 MHz,
J¼7.5 Hz), 7.41 ( 4H, d, J¼7.7 Hz), 7.32 ( 4H, d, J¼7.5 Hz), 6.97 ( 4H, d,
CDCl3):
1687.
d
191.3, 135.9, 132.3, 129.6, 128.7, 92.1; IR (neat, cmꢁ1)3080,
J¼7.7 Hz), 2.45 (6H, s); 13C NMR (100 MHz, CDCl3):
d 149.4, 145.6,
132.9,129.8,128.5,122.6,121.9, 90.0, 21.7; IR (neat, cmꢁ1)3039, 2920,
1590;HRMS(ESI)calcdforC28H22O6S2Na, 541.0750;found, 541.0756.
4.2.13. N,N0-(4,40-(Ethyne-1,2-diyl)bis(4,1-phenylene))diacetamide
(2n). Synthesized according to general procedure from N-(2-
iodophenyl)acetamide (200 mg, 0.766 mmol), calcium carbide
4.2.19. Dimethyl 4,40-(4,40-(ethyne-1,2-diyl)bis(2,5-dibutoxy-4,1-
phenylene))bis(ethyne-2,1-diyl)dibenzoate (2t). Synthesized according

8182
P. Chuentragool et al. / Tetrahedron 67 (2011) 8177e8182
to general procedure from methyl 4-((2,5-dibutoxy-4-iodophenyl)
ethynyl)benzoate 1t (200 mg, 0.407 mmol), calcium carbide (78.3 mg,
1.22 mmol), copper iodide (7.8 mg, 0.041 mmol), palladium(II)acetate
(4.6 mg, 0.020 mmol), triphenylphosphine (10.7 mg, 0.041 mmol), and
triethylamine (123 mg, 1.22 mmol) and purified by flash chromatog-
raphy to afford 133.4 mg (0.171 mmol, 87.1%) of 2t as a yellow solid: 1H
InChiKeys of the most important compounds described in this
article.
References and notes
NMR (400 MHz, CDCl3):
d
ppm 8.03 ( 4H, d, J¼8.2 Hz), 7.58 ( 4H, d,
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1.89e1.78 (8H, m), 1.62e1.53 (9H, m), 1.05e0.95 (12H, m); 13C NMR
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(100 MHz, CDCl3): d 166.6, 153.8, 153.5, 131.4, 131.4, 129.5, 129.4, 128.2,
117.1, 117.1, 114.9, 113.4, 94.1, 91.7, 89.1, 69.5, 69.3, 52.2, 31.4, 31.4, 19.3,
13.9, 13.9; IR (neat, cmꢁ1)2956, 2864, 2205; HRMS (ESI) calcd for
C50H54O8Na, 805.3711; found, 805.3713.
4.2.20. Dimethyl 4,40-(4,40-(ethyne-1,2-diyl)bis(2,5-dibutoxy-4,1-
phenylene))bis(ethyne-2,1-diyl)dibenzoate (2u). Synthesized accord-
ing to general procedure from 3,30-(2-iodo-5-((4-(methoxycarbonyl)
phenyl)ethynyl)-1,4-phenylene)bis(oxy)bis(propane-3,1-diyl)diac-
etate 1u (100 mg, 0.166 mmol), calcium carbide (32.4 mg,
0.50 mmol), copper iodide (3.2 mg, 0.017 mmol), palladium(II)ace-
tate (1.9 mg, 0.009 mmol), triphenylphosphine (4.4 mg, 0.017 mmol),
and triethylamine (50.1 mg, 0.5 mmol) and purified by flash chro-
matography to afford 17.8 mg (0.019 mmol, 50.8%) of 2u as a yellow
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solid: 1H NMR (400 MHz, CDCl3):
d
ppm 8.03 ( 4H, d, J¼8.2 Hz), 7.60
( 4H, d, J¼8.2 Hz), 7.04 ( 4H, d, J¼6.9 Hz), 4.38e4.31 (8H, m),
4.18e4.11 (8H, m), 3.93 (6H, s), 2.23e2.14 (8H, m), 2.07e2.03 (12H,
m); 13C NMR (100 MHz, CDCl3):
d
171.0, 170.9, 166.5, 153.6, 153.2,
131.5, 131.5, 129.6, 127.9, 117.2, 117.1, 114.7, 113.7, 94.5, 91.5, 88.5, 66.1,
66.0, 61.3, 61.2, 61.2, 61.1, 52.2, 28.75, 28.7, 20.9, 20.9; IR (neat, cmꢁ1
)
3059, 2205, 1702; HRMS (ESI) calcd for C50H54O16Na, 981.3304;
found, 981.3308.
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This study is financially supported by the Thailand Research
Fund (TRF-RSA5480004) and National Nanotechnology Center
(NANOTEC), NSTDA (NN-B-22-FN9-10-52-06). This work is part of
the Project for Establishment of Comprehensive Center for In-
novative Food, Health Products and Agriculture supported by the
Thai Government Stimulus Package 2 (TKK2555, SP2), The Asahi
Glass Foundation, and also the National Research University Project
of CHE (AM1006A).
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Supplementary data
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Images of 1H and 13C NMR spectrum of compounds 2aeu are
available in the Supplementary data. Supplementary data associ-
ated with this article can be found in the online version, at
doi:10.1016/j.tet.2011.08.042. These data include MOL files and