An improved practical Pd/C-catalyzed Sonogashira cross-coupling reaction for the synthesis of liquid crystals of trans-cyclohexyltolans

Article abstract of DOI:10.1002/aoc.1642

An improved practical synthesis of liquid crystals of trans- cyclohexyltolans by Sonogashira cross-coupling reaction of 1-iodo- 4-(trans-4-alkylcyclohexyl)benzene with aromatic terminal alkynes in the presence of Pd/C (palladium on activated carbon) as low as 0.03mol% of Pd and CuI (2mol%) in amixture solvent of acetone-water (5 : 2 in volume) is described. The liquid crystals could be obtained in high yields as a solid with excellent purity by simple filtration, and the filtrate could be reused several times while still retaining high catalytic activity. Copyright

Full text of DOI:10.1002/aoc.1642

Full Paper
Received: 19 December 2009
Revised: 4 February 2010
Accepted: 7 February 2010
Published online in Wiley Interscience: 22 March 2010
(www.interscience.com) DOI 10.1002/aoc.1642
An improved practical Pd/C-catalyzed
Sonogashira cross-coupling reaction
for the synthesis of liquid crystals
of trans-cyclohexyltolans
Hongyong Shanga,b, Ruimao Huaa∗, Qingwei Zhenga, Jianli Zhangb,
Xiao Lianga,b and Qiming Zhub
An improved practical synthesis of liquid crystals of trans-cyclohexyltolans by Sonogashira cross-coupling reaction of 1-iodo-
4-(trans-4-alkylcyclohexyl)benzene with aromatic terminal alkynes in the presence of Pd/C (palladium on activated carbon) as
low as 0.03 mol% of Pd and CuI (2 mol%) in a mixture solvent of acetone–water (5 : 2 in volume) is described. The liquid crystals
could be obtained in high yields as a solid with excellent purity by simple filtration, and the filtrate could be reused several
c
times while still retaining high catalytic activity. Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: Pd/C; cuprous iodide; cross-coupling reaction; cyclohexyltolans; liquid crystals
Introduction
most suitable catalyst in industrial processes because of its low
cost and stability. Therefore, recent attempts have been made in
our research group to improve the Sonogashira cross-coupling re-
action of 1-iodo-4-(trans-4-alkylcyclohexyl)benzene with aromatic
terminal alkynes to synthesize the trans-cyclohexyltolan-type liq-
uid crystals catalyzed by Pd/C and CuI, and our results are reported
in this paper (Scheme 1).
Palladium/copper-catalyzed Sonogashira cross-coupling reaction
of terminal alkynes with aryl halides has evolved as a powerful
method for constructing carbon–carbon bonds,[1–3] and has
been applied as the key step in the synthesis of liquid crystals
involving the structural unit of diarylacetylene. Pd(PPh3)4 and
PdCl2(PPh3)2 are two catalysts commonly used in the industrial
production of liquid crystals. However, their disadvantages
include the occurrence of several side-reactions such as oxidative
homocoupling, dimerizationandtrimerizationofterminalalkynes,
as well as dehalogenative hydrogenation of aryl halides. The
formation of a considerable amount of by-products from the
above-mentioned side-reactions usually resulted not only in the
tedious purification of liquid crystals, but also in the decrease in
quality of the liquid crystals, and low economic efficiency.
Inrecentyears,wehavebeeninterestedinthesynthesisoftrans-
cyclohexyltolan-type liquid crystals, which have the properties of
low viscosity coefficients, higher phase transition temperature
and higher optical anisotropy (ꢀn),[4–7] by the Sonogashira cross-
coupling reaction of 1-iodo-4-(trans-4-alkylcyclohexyl)benzene
with aromatic terminal alkynes catalyzed by Pd(PPh3)4 or
PdCl2(PPh3)2 with CuI as co-catalyst in both the academic and
industrial settings.[8–10] One of the most important topics in our
research group is the development of an alternative catalyst
system which aims to suppress side reactions, improve liquid
crystal quality, and decrease production cost.
Results and Discussion
Table 1 concludes the catalytic activity of Pd/C under differ-
ent reaction conditions in the reaction of 1-iodo-4-(trans-4-
propylcyclohexyl)benzene (1a) with 4-methoxyphenyl acetylene
(2a). When a mixture of 1a and 2a (1.1 equiv.) in THF was
refluxed in the presence of 5% Pd/C (0.0006 equiv), CuI (0.05
equiv), PPh3 (0.006 equiv) and Et3N (3.0 equiv) under nitrogen for
3 h, the desired coupling product 3a was obtained in 75% GC yield
(entry 1, GC yield was based on the amount of 1a employed by
adding the internal standard material). In this case, the conversion
of 1a was 80%. When DMF was used as a solvent (at 90 ◦C) to
replace THF, the yield of 3a could be slightly improved (entry 2).
The use of a solvent mixture of DMF and H2O (1 : 1 in volume, at
93 ◦C) resulted in the complete conversion of 1a, and the GC yield
∗
Correspondenceto:Ruimao Hua,TinghuaUniversity,DepartmentofChemistry,
It is well known that Pd/C can be used as a catalyst in carbon-
carbon coupling reactions to replace homogeneous palladium
catalysts.[11–13] Since the first example of Sonogashira cross-
coupling reactioncatalyzedbyPd/Cwasreported,[14] afewreports
on the Sonogashira cross-coupling reactions catalyzed by Pd/C
have appeared in the literature.[15–18] Pd/C is considered to be the
Tsinghua University, Beijing 100084, China.
E-mail: ruimao@mail.tsinghua.edu.cn
a
Department of Chemistry, Tsinghua University, Beijing 100084, China
b
Shijiazhuang (Developed Zone) Yongsheng Huatsing Liquid Crystal Co. Ltd,
Shijiazhuang 050091, China
c
Appl. Organometal. Chem. 2010, 24, 473–476
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

H. Shang et al.
R
Known process:
Pd(0) or Pd(II), CuI
R
+
This study: Pd/C, CuI
I
R
R
Scheme 1. Synthesis of liquid crystals by Sonogashira cross-coupling reaction.
Table 1. Cross-coupling reaction of 1-iodo-4-(trans-4-propylcyclohexyl)benzene (1a) with 4-methoxyphenyl acetylene (2a)a
Pd, CuI, PPh3
n-C3H7
+
OMe
N2, solvent, Et3N
reflux for 3 h
I
1a
n-C3H7
2a
1 : 1.1
3a
OMe
Entry
1
Catalyst (Pd mol%)
Solvent
Other conditions
GC yield (%)b
75
Pd/C (0.06)
Pd/C (0.06)
Pd/C (0.06)
Pd/C (0.06)
Pd/C (0.03)
Pd/C (0.03)
THF
Cul (5 mol%), PPh3 (0.6 mol%)
Et3N (3 equiv), reflux (64 ◦C)
Cul (5 mol%), PPh3 (0.6 mol%)
Et3N (3 equiv), reflux (90 ◦C)
Cul (5 mol%), PPh3 (0.6 mol%)
Et3N (3 equiv), reflux (93 ◦C)
Cul (2 mol%), PPh3 (0.6 mol%)
Et3N (3 equiv), reflux (93 ◦C)
Cul (2 mol%), PPh3 (0.6 mol%)
Et3N (3 equiv), reflux (63 ◦C)
Cul (1 mol%), PPh3 (0.6 mol%)
Et3N (3 equiv), reflux (63 ◦C)
2
3
4
5
6
DMF
80
90
DMF/H2O
(1 : 1 v/v)
DMF/H2O
(5 : 2 v/v)
> 99
> 99 (93)
96
acetone/H2O
(5 : 2 v/v)
acetone/H2O
(5 : 2 v/v)
a Reactions were carried out using 25.0 mmol of 1a, 27.5 mmol of 2a in 70 mL of solvent under reflux for 3 h.
b GC yield based on 1a used. Number in parenthesis was isolated yield.
of 3a was increased to 90% (entry 3). A quantitative yield of 3a
could be achieved when a mixture solvent of DMF and H2O in a
ratio of 5 : 2 (in volume) was used, even if the amount of CuI was
reduced to 0.02 equivalent (entry 4). It was found that a mixture
solvent of acetone and water in a ratio of 5 : 2 (in volume) was
the better solvent for the present cross-coupling reaction and the
amount of Pd/C could be reduced to 0.0003 equiv. without any
significant decrease in the yield of 3a. As shown in entries 5 and 6,
although 0.0003 equiv. of Pd/C and 0.01 equiv. of CuI also worked
sufficiently, the use of 0.0003 equiv. of Pd/C and 0.02 equiv. of
CuI realized the quantitative yield with good reproducibility. It
is most notable that, when the reaction mixture was cooled to
room temperature, 3a was precipitated as crystals, and it could be
isolated in 93% yield with high purity by simple filtration (entry
5). It is also important to point out that under theses reaction
conditions only trace amounts of 1,4-diaryl-1,3-diyne and dimer of
2a could be found in the filtrate.
cross-coupling reactions smoothly, affording the desired coupling
products 3b–e in 80–89% isolated yields with high purity. Under
the same reaction conditions, the cross-coupling reaction of 1c
with 2a also proceeded efficiently to give the corresponding
coupling product 3f in 83% isolated yield.
The high catalytic activity of the present catalyst system is
considered to result from the leaching of Pd from Pd/C and
complete solubility of Pd as homogeneous catalyst under the
chosen reaction conditions. Indeed, the filtrate could be directly
reused as the palladium catalyst source after filtering out the
coupling products. As an example, after separation of 3a by
filtration from the reaction mixture indicated in entry 5 of Table 1,
the additional amounts of 1a (25.0 mmol), 2a (27.5 mmol) and
Et3N (3 equiv.) were added, and the mixture was refluxed for 9 h.
When the reaction mixture was cooled to room temperature, 3a
was again isolated in 89% yield by filtration.
Table 2 shows the results of the cross-coupling reactions of aryl
iodides 1a and 1b with aromatic terminal alkynes 2a–d under
the reaction conditions indicated in entry 5 of Table 1. Aromatic
terminal alkynes bearing both an electron-donating group and an
electron-withdrawing group(s) in the benzene ring underwent the
Conclusion
In conclusion, we have demonstrated that Pd/C in a mixture
solvent of acetone and water (5 : 2 in volume) shows excellent
c
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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 473–476

An improved practical Pd/C-catalyzed Sonogashira cross-coupling reaction
Shimadzu GCMS-QP2010S. Element analyses were obtained with
a Flash EA 1112 Element Analyzer.
Table 2. Synthesis of liquid crystals via Sonogashira cross-coupling
reactiona
R′
R′
5% Pd/C (0.03 mol%)
CuI (2 mol%), PPh3
Typical Experimental Procedure for the Synthesis
of trans-Cyclohexyltolan (3a) (Table 1, entry 5)
R
I
R
+
acetone/H2O (5:2 v/v)
60-65°C for 3 h
1
25.0 mmol
2
27.5 mmol
A mixture of 1-iodo-4-(trans-4-propylcyclohexyl)benzene (1a)
(8.2 g, 25.0 mmol), 4-methoxyphenyl acetylene (2a) (3.65 g,
27.5 mmol), 5%Pd/C(0.05 g, 66%waterwet, 0.03 mol%), CuI(0.1 g,
2 mol%), PPh3 (0.04 g, 0.6 mol%) and Et3N (7.6 g, 75.0 mmol) in
acetone (50 ml) and H2O (20 ml) under nitrogen was refluxed (at
ca 64 ◦C) for 3 h. After the reaction mixture was cooled to room
temperature, 3a (7.72 g, 23.3 mmol, 93%, purity is 99.7%) as white
precipitate was isolated by filtration.
For GC analysis, a parallel reaction was carried out, and the
solvents and volatiles were directly removed under vacuum. The
obtained residue was resolved in toluene (200 ml) and biphenyl
(0.77 g, 5.0 mmol) was added as internal standard for GC analysis.
It was found that 3a was formed in almost quantitative yield.
Compounds 3e and 3f are new, and were characterized by
1H, 13C-NMR, mass spectra and elemental analysis. Other known
coupling products were characterized by 1H, 13C-NMR and mass
spectra. The spectroscopic data of 3e and 3f are reported below.
n-C3H7
R: n-C5H11
R:
1c
1b
R' = p-Me, 2b; p-Cl, 2c; 2, 6-difluro-4-n-propyl, 2d
Isolated
yield (%)
Purity
(%)b
Product
89
85
80
88
99.4
99.8
98.2
99.8
n-C5H11
3b
OMe
n-C3H7
n-C3H7
n-C3H7
n-C3H7
3c
3d
Me
Cl
1-(2,6-Difluoro-4-n-propylphenylethynyl)-4-(4-n-propylcyclohexyl)
benzene 3e
White solid, mp 74.5–76.3 ◦C; 1H NMR (300 MHz, CDCl3) δ7.48 (d,
2H, J = 8.3 Hz, 2 × CH arom.), 7.18 (d, 2H, J = 7.9 Hz, 2 × CH
arom), 6.73 (d, 2H, J = 7.9 Hz, 2 × CH arom), 2.56 (t, 2H, J = 7.6 Hz,
CH3CH2CH2), 2.50–2.42 (m, 1H, CH), 1.87–1.80 (m, 4H, 2 × CH2),
1.66–1.58 (m, 2H, CH2), 1.50–1.16 (m, 7H, 3 × CH2 and CH),
1.10–0.85 (m, 8H, CH2 and 2 × CH3); 13C NMR (75 MHz, CDCl3) δ
F
3e
n-C3H7
OMe
F
83
99.8
3f
162.8 (dd, J1
= 256.7 Hz, J3
= 6.45 Hz, ipso-C of CF), 148.9
C−F
a Reaction conditions: Pd (0.03 mol%, 5% on activated carbon, 66%
water wet), Cul (2 mol%), PPh3 (0.6 mol%), Et3N (75.0 mmol), acetone
(50 mL), H2O (20 mL), 60–65 ◦C (under refluxing) for 3 h.
b Determined by GC.
C−F
(ipso-Carom), 145.8(t, J2
= 8.6 Hz, ipso-Carom), 131.8(Carom),
C−F
127.0 (C arom), 120.2 (ipso-C arom), 111.4–111.1 (m, ipso-C and C
arom), 99.8 (t, J3
= 20.1 Hz, C–C), 98.7 (C–C), 44.8 (CH), 39.8
C−F
(CH), 37.9 (CH2), 37.1 (CH2), 34.3 (2C, 2 × CH2), 33.6 (2C, 2 × CH2),
23.9 (CH2), 20.2 (CH2), 14.5 (CH3CH2CH2), 13.7 (CH3CH2CH2); GCMS
m/z (% rel. inten.) 380 (M+, 100), 351 (3), 295 (15), 282 (30), 267 (8),
253 (41), 240 (13), 207 (9), 169 (3), 115 (2), 81 (6); anal. calcd for
C26H30F2: C, 82.11; H, 7.89. Found: C, 82.67; H, 7.91.
catalytic activity for the Sonogashira cross-coupling reaction of
1-iodo-4-(trans-4-alkylcyclohexyl)benzene with aromatic termi-
nal alkynes to afford liquid crystals of trans-cyclohexyltolans.
The advantages of the present catalytic system include cost-
effectiveness, a simple procedure for product isolation, high yields
and excellent purity, as well as the reuse of the filtrate as the
catalyst source. Compared with previously reported systems,
the present system is cheaper and more practical, and seems
promising in future industrial, large-scale production of liquid
crystals.
4-(4-Methoxyphenylethynyl)-4’-n-propyl-biphenyl3f
White solid, m.p. 154.7–156.5 ◦C; 1H NMR (300 MHz, CDCl3) δ
7.54–7.45 (m, 8H, 8 × CH arom.), 7.24 (d, 2H, J = 7.9 Hz, 2 × CH
arom), 6.86 (d, 2H, J = 8.6 Hz, 2×CH arom), 3.79 (s, 3H, OCH3), 2.62
(t, 2H, J = 7.2 Hz, CH3CH2CH2), 1.70–1.63 (m, 2H, CH3CH2CH2),
0.96 (t, 3H, J = 7.2 Hz, CH3CH2CH2); 13C NMR (75 MHz, CDCl3)
δ 159.7 (ipso-C arom), 142.4 (ipso-C arom), 140.7 (ipso-C arom),
137.8 (ipso-C arom), 133.2 (C arom), 131.9 (C arom), 129.1 (C arom),
126.9 (C arom), 122.3 (ipso-C arom), 115.6 (ipso-C arom), 114.1
(C arom), 90.1 (C–C), 88.3 (C–C), 55.4 (OCH3), 37.8 (CH3CH2CH2),
24.7 (CH3CH2CH2), 14.0 (CH3CH2CH2); GCMS m/z (% rel. inten.) 326
(M+, 97), 297 (70), 282 (23), 254 (23), 237 (9), 207 (100), 149 (30),
127 (14), 96 (15); anal. calcd for C24H22O: C, 88.34; H, 6.75. Found:
C, 88.47; H, 6.61.
Experimental
General Methods
All organic starting materials are chemically pure and were
used without further purification. H and 13C NMR spectra were
recorded on Joel JNM-ECA300 spectrometers at 300 and 75 MHz,
1
1
respectively. H chemical shifts (δ) were referenced to TMS, and
Acknowledgments
13C NMR chemical shifts (δ) were referenced to internal solvent
resonance. GC analyses of organic compounds were performed
on an Agilent 6890N instrument. Mass spectra were obtained on a
The authors greatly thank Miss Maria Victoria Abrenica, from
Wellesley College, for her kind English proofreading.
c
Appl. Organometal. Chem. 2010, 24, 473–476
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/aoc

H. Shang et al.
Supporting Information
[7] K. Shibata, S. Matsui, H. Takeuchi, K. Kawano, Y. Kubo, E. Nakagawa,
European Patent 1 149 885 A1, 2001.
[8] B. Chen, G. Sun, S. Xu, Liq. Cryst. 2004, 31, 421.
[9] B. Chen, G. Sun, S. Xu, Liq. Cryst. 2004, 31, 767.
[10] X. Liang, H. Tang, W. Zhang, B. Zhang, CN Patent 1730452-A, 2006.
[11] M. Seki, Synthesis 2006, 2975.
Supporting information of the general method, characterization
1
data and charts of H- and 13C-NMR for all the products may be
found in the online version of this article.
[12] F.-X. Felpin, T. Ayad, S. Mitra, Eur. J. Org. Chem. 2006, 2679.
[13] L. Yin, J. Liebscher, Chem. Rev. 2007, 107, 133.
[14] M. A. De la Rosa, E. Velarde, A. Guzma´n, Synth. Commun. 1990, 20,
2059.
References
[15] L. Bleicher, N. D. P. Cosford, Synlett 1995, 1115.
[16] Z. Nova´k, A. Szabo´, J. Re´pa´si. A. Kotschy, J. Org. Chem. 2003, 68,
3327.
[17] V. R.Batchu,V.Subramanian,K.Parasuraman,N. K.Swamy,S. Kumar,
M. Pal, Tetrahedron 2005, 61, 9869.
[1] K. Sonogashira, J. Organomet. Chem. 2002, 653, 46.
[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.
[4] R. Eidenschink, D. Erdmann, J. Krause, L. Pohl, Angew. Chem. Int. Ed.
Engl. 1977, 16, 100.
[18] S. Mori, T. Yanase, S. Aoyagi, Y. Monguchi, T. Maegawa, H. Sajiki,
Chem. Eur. J. 2008, 14, 6994.
[5] Y. Goto, T. Ogawa, European Patent 0 255 700 A2, 1987.
[6] H. Takatsu, M. Sasaki, Y. Tanaka, H. Sato, US Patent 4 705 870, 1987.
c
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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 473–476