Copper- and amine-free sonogashira-hagihara coupling reaction catalyzed by Pd(0) nanoparticles supported on modified crosslinked polyacrylamide

Article abstract of DOI:10.1135/cccc2011168

Pd(0) nanoparticles supported on modified crosslinked polyacrylamide containing phosphinite ligand was prepared. The complex was a highly efficient catalyst for the Sonogashira- Hagihara coupling reaction in the absence of a copper cocatalyst and an amine

Full text of DOI:10.1135/cccc2011168

Sonogashira Reaction Catalyzed by Supported Catalyst
1967
COPPER- AND AMINE-FREE SONOGASHIRA–HAGIHARA COUPLING
REACTION CATALYZED BY Pd(0) NANOPARTICLES SUPPORTED
ON MODIFIED CROSSLINKED POLYACRYLAMIDE
1,
2
Bahman TAMAMI * and Soheila GHASEMI
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran;
1
2
e-mail: tamami@chem.susc.ac.ir, soheila_ghasemi_chem@yahoo.com
Received August 24, 2011
Accepted October 31, 2011
Published online January 30, 2012
Pd(0) nanoparticles supported on modified crosslinked polyacrylamide containing phosphi-
nite ligand was prepared. The complex was a highly efficient catalyst for the Sonogashira–
Hagihara coupling reaction in the absence of a copper cocatalyst and an amine base under
aerobic condition. This protocol can be applied for different aryl halides including chloro-
arenes. The catalyst can be reused several times without any considerable decrease in its ac-
tivity because of low leaching of palladium metal from the support. Transmission electron
microscopy (TEM) analysis of the catalyst revealed the formation of stable and polydispersed
Pd(0) nanoparticles.
Keywords: C–C Coupling; Heterogeneous catalysis; Palladium nanoparticle; Polyacrylamide
support; Sonogashira coupling; Leaching.
Sonogashira coupling reaction of terminal alkynes with aryl or vinyl halides
is a powerful method in organic synthesis for construction of carbon–
carbon bond1. The reaction directly provides an efficient rout to unique
organic compounds having the C(sp2)–C(sp) bond which has been widely
utilized in areas such as natural product synthesis, pharmaceutical and ma-
terial science2.
Since its first report in 1975 3, the reaction has been well studied. The
most commonly used catalytic systems for this transformation include vari-
ety of homogenous palladium complexes together with copper salt as a co-
catalyst and large amount of amine as the solvent or cosolvent4. Although,
the presence of the copper salts facilitates the coupling reaction by genera-
tion of copper acetylide, it can also induce a Glaser-type oxidative homo-
coupling of the terminal acetylene to the corresponding symmetrical
diyne5. In order to reduce diacetylene formation, various copper-free meth-
odologies have been reported6,7. However, many of these methodologies
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 12, pp. 1967–1978
© 2011 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc2011168

1968
Tamami, Ghasemi:
may suffer from different problems. Most of them involve the use of
amines such as piperidine, triethylamine or pyrrolidone in large excess or
as a solvent8. The reactions are generally performed in the presence of ho-
mogenous palladium catalysts, which make the catalyst recovery a tedious
procedure and may result in contamination of products by metallic species.
Furthermore, many of these methods are applied for aryl iodides and acti-
vated aryl bromides but rarely for aryl chlorides. Other drawbacks can be:
using high palladium catalyst loading, performing the reaction under an-
aerobic condition and using palladium complex or ligand that are expen-
sive or hard to make. In this regard, numerous modifications have been
reported for the Sonogashira coupling reactions recently. Some of them are:
reactions in ionic liquid9, reactions in neat water10, use of palladacycle cata-
lyst or N-heterocyclic carbene (NHC) ligands11, incorporating mesoporous
material such as MCM-41 12, solvent-free condition13, microwave irradia-
tion14, phase transfer catalytic reaction condition15, use of fluorous bi-
phasic catalysis (FBC) system16, reactions under ligand-free condition17, or
microemulsion systems18, etc. In view of all these facts, despite that the
Sonogashira coupling reaction has been intensively studied; there are only
few examples of the heterogeneous palladium catalyst systems for the
Sonogashira coupling of aryl chlorides which can act under copper-free
condition19. Thus, the study of new types of polymer-supported palladium
catalysts which might be suitable for the Sonogashira reaction of all aryl
halides especially less active ones has practical significance.
In continuation of our previous studies on the use of modified poly-
acrylamide resins as heterogeneous supports20, we recently introduced
novel Pd(0) nanoparticles supported on modified crosslink polyacrylamide
as a catalyst for the Heck and Suzuki coupling reactions21. Hereby, we pres-
ent new application of this catalyst for a highly efficient copper- and
amine-free Sonogashira reaction of a wide variety of aryl halides including
aryl chlorides.
RESULTS AND DISCUSSION
Phosphinites are potential ligands for the formation of palladium com-
plexes that can be used as catalysts in carbon-carbon bond formation reac-
tions22. These ligands stabilize palladium and increase its reactivity. They
indebted their efficiency in these reactions to their bulkiness and electron-
richness. In this study, we have introduced palladium nanoparticles sup-
ported on modified crosslinked polyacrylamide containing phosphinite
ligand as an efficient polymeric catalyst for Sonogashira–Hagihara coupling
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 12, pp. 1967–1978

Sonogashira Reaction Catalyzed by Supported Catalyst
1969
reactions. The polymeric phosphinite ligand was obtained by transamid-
ation reaction of crosslinked polyacrylamide (5% with N,N′-methylene-
bis-acrylamide) with hydroxylamine and its subsequent reaction with
chlorodiphenylphosphine. This polymeric ligand was complexed with
Pd(OAc)2 to obtain the heterogeneous catalytic system (Scheme 1). Scan-
ning electron microscopy (SEM) and transmission electron microscopy
(TEM) images of the catalyst showed palladium dispersion with a well de-
gree of homogeneity in nanometer size21. The formation of active Pd(0)
nanoparticles was revealed by its X-ray diffraction (XRD), TEM image and
UV-Vis diffuse reflectance spectrum (UVDR) in our previous report21. The
XRD patterns of the catalyst showed the characteristic bands for the forma-
tion of Pd(0) at (111), (200), (220) and (311) crystallographic planes. The
absence of d→d transition in UVDR spectrum was also attributed to metal-
lic Pd(0) complex21.
SCHEME 1
Optimization of Reaction Condition for Sonogashira Reaction
To optimize the reaction condition, we chose iodobenzene and phenyl-
acetylene as a model coupling partners. Initial screening of the reaction re-
vealed that 0.5 mole % of the catalyst was sufficient to induce coupling
reaction for aryl iodides and bromides, while 1 mole % is necessary for cou-
pling of less active aryl chlorides. Furthermore, the reactions need tetra-
butylammonium bromide (TBAB) (Jeffery catalyst) as an additive. Although
the effect of TBAB in the coupling reactions is not completely clear, but it
acts as a base and phase transfer catalyst to accelerate these reactions. In ad-
dition, TBAB facilitate the regeneration of the zerovalent palladium in the
catalytic cycles23. The influence of solvent on the Sonogashira coupling re-
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Tamami, Ghasemi:
action of the model substrates was examined over the catalyst as shown in
Table I. Among the solvents used, high catalytic activity was observed in
NMP and DMF. However, the reaction in DMF produced homo-coupled
dialkyne and needed longer reaction time. The use of EtOH and THF as sol-
vents led to slower reaction, and no product was obtained when the reac-
tion was carried out in CH3CN. Table II shows the influence of base for the
model reaction. As mentioned in the literature, the use of a base in the
Sonogashira reaction not only is necessary for absorption of hydrogen
halides, but also is important in inhibiting homo-coupling product forma-
tion24. No coupling reaction occurred in the absence of a base. Among
TABLE I
Effect of different solvents on the Sonogashira coupling of iodobenzene with phenyl-
acetylenea
Entry
Solvent
Time, h
Conversion, %b
1
2
3
4
5
DMF
6
4
6
6
6
100
100
75
NMP
THF
EtOH
CH3CN
70
trace
a
Reaction condition: aryl halide (1.0 mmol), phenylacetylene (1.2 mmol), K2CO3
b
(2.0 mmol), Pd catalyst (0.5 mole %), TBAB (5 mole %) in solvent (5 ml) at 100 °C. Con-
version based on iodobenzene.
TABLE II
Effect of different bases on the Sonogashira coupling of iodobenzene with phenylacetylenea
Entry
Base
Time, h
Conversion, %b
1
2
3
4
5
–
6
6
4
6
6
trace
60
Et3N
K2CO3
100
50
KF
Na3PO4·12H2O
100
a
Reaction condition: aryl halide (1.0 mmol), phenylacetylene (1.2 mmol), base (2.0 mmol),
b
Pd catalyst (0.5 mole %), TBAB (5 mole %) in NMP (5 ml) at 100 °C. Conversion based on
iodobenzene.
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Sonogashira Reaction Catalyzed by Supported Catalyst
1971
bases tested, K2CO3 was the best choice. It gave quantitative conversion of
iodobenzene without considerable formation of homo-coupling product.
Other bases such as Et3N, KF and Na3PO4·12H2O were explored and proved
to be inferior. In all, 0.5 mole % of polymeric catalyst/K2CO3/5 mole % TBAB
in NMP at 100 °C considered as an optimum catalyst system for aryl iodides
and bromides and 1 mole % of the catalyst loading for aryl chlorides.
The Sonogashira–Hagihara Coupling Reaction of Aryl Halides
with Terminal Alkynes
To examine the scope and limitation of Sonogashira coupling reaction, a
variety of aryl halides were coupled with terminal alkynes under optimized
condition and produced excellent to moderate yield of the coupling prod-
ucts (Scheme 2), although, homo-coupled product was also formed to an
extent of 6–9%. The results are recorded in Table III. It is observed that the
process tolerates both electron-donating and electron-withdrawing groups
in the aryl halides. Heterocyclic substituent was also tolerated (entry 13).
The reactions of less active aryl chlorides need longer reaction times and
more palladium loading (entries 14–17).
SCHEME 2
A Pd(0) species stabilized by ligands is proposed in the catalytic cycle of
Sonogashira reaction. In our catalytic cycle, the formation of such Pd(0)
nanoparticles was revealed by TEM analysis of the catalyst after a
Sonogashira reaction between iodobenzene and phenyl acetylene (Fig. 1).
The TEM image shows the presence of polydispersed Pd(0) nanoparticles
varying in size from 30–50 nm.
On the basis of the general mechanism reported earlier in the litera-
ture13b,23b,24c, a mechanism for this Sonogashira cross-coupling reaction is
outlined in Scheme 3. The Pd(0) species could be generated from the reac-
tion of Pd(OAc)2 with polymeric ligand (L) in step 1. After oxidative addi-
tion of aryl halides to Pd(0) in step 2, insertion of the triple bond to
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Tamami, Ghasemi:
TABLE III
Palladium catalyzed Sonogashira coupling reaction of aryl halides with terminal alkynesa
Entry
1
Aryl halide
R2
Product
1a
Time, h
Yield, %b
I
Ph
4
90
I
2
3
4
5
6
7
8
9
CH2OH
Ph
1b
1c
1d
1a
1b
1e
1f
5
85
89
80
87
82
75
80
86
MeO
I
7
MeO
I
CH2OH
Ph
7
Br
8
Br
CH2OH
Ph
12
4
O2N
O2N
Br
Br
CH2OH
Ph
5
1g
4
NC
Br
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Sonogashira Reaction Catalyzed by Supported Catalyst
1973
TABLE III
(Continued)
Entry
10
Aryl halide
R2
Product
1h
Time, h
Yield, %b
Cl
Br
Ph
6
85
80
80
85
70
78
72
70
MeOC
Br
11
Ph
Ph
Ph
Ph
Ph
Ph
Ph
1i
7
Me
N
Br
12
1j
1k
3a
3e
3i
12
8
Br
13
14c
15c
16c
17c
24
9
Cl
O2N
Cl
18
24
MeOC
Me
Cl
Cl
3j
a
Reaction condition: aryl halide (1.0 mmol), terminal alkyne (1.2 mmol), K2CO3 (2.0 mmol),
b
c
Pd catalyst (0.5–1 mole %), TBAB (5 mole %) in NMP (5 ml) at 100 °C. Isolated yield. Pd
catalyst (1 mole %).
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Tamami, Ghasemi:
Ar-Pd-X generates the alkenylpalladium (step 3) which undergoes β-hydride
elimination (step 4) to afford disubstituted alkynes. The Pd(0) species is re-
generated by reductive elimination of the Pd(II) compound in the presence
of a base in the final step 5. TBAB has promoting influence in this cycle by
assistance in the regeneration of zerovalent palladium catalyst in step 5.
Several possible mechanisms proposed by Jeffery in this matter23.
SCHEME 3
FIG. 1
TEM image of the catalyst after a Sonogashira reaction of iodobenzene with phenyl acetylene
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 12, pp. 1967–1978

Sonogashira Reaction Catalyzed by Supported Catalyst
1975
The Recyclability and Heterogeneity Test of the Catalyst
We also examined the reuse of the catalyst in the reaction of iodobenzene
with phenylacetylene. The catalyst was recycled for five cycles in this reac-
tion to record a TON of 860 and average TOF (h–1) of 31.8 in total for five
runs. The yield of the product gradually decreased from 91% for the first
run to 82% for the fifth run as shown in Fig. 2. Therefore, there is no sig-
nificant loss of the catalytic activity during these cycles and the catalyst
showed good reusability.
Immobilized metal catalysts often suffer from leaching of metal species
during the course of reaction. To probe the issue of palladium leaching in
our system, the filtrate of the reaction between iodobenzene and phenyl-
acetylene was analyzed by ICP. Analysis of the crude reaction mixture indi-
cates a total leaching of 4.8% of the palladium for the whole recycling
processes. These results indicate low leaching of palladium into the solu-
tion.
For further investigation, in order to ascertain whether the catalyst was
behaving in a truly heterogeneous manner, or whether it is merely a reser-
voir for more active soluble form of Pd, hot filtration test was performed25.
We repeated the reaction between iodobenzene and phenylacetylene and
filtered the catalyst after 25% conversion, and allowed the reaction to con-
tinue in the absence of catalyst. No additional conversion was seen after fil-
tration of the catalyst26. This confirmed the heterogeneous character of the
catalytically active species in this reaction.
FIG. 2
Reusability of polymer supported Pd(0) catalyst in the Sonogashira coupling reaction. Reaction
condition: iodobenzene (1.0 mmol), phenylacetylene (1.2 mmol), K2CO3 (2.0 mmol), Pd cata-
lyst (0.5 mole %), TBAB (5 mole %) in NMP (5 ml) at 100 °C
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Tamami, Ghasemi:
CONCLUSION
In conclusion, we have shown the applicability of zerovalent Pd nano-
particles supported on modified crosslinked polyacrylamide as an efficient
and practical catalyst for the copper- and amine-free Sonogashira reaction
in NMP under aerobic condition. This catalyst can be recovered and reused
several times without considerable loss of activity because of negligible
leaching of palladium from supported system. The TEM image of the cata-
lyst shows the presence of polydispersed Pd(0) nanoparticles for the reac-
tion.
EXPERIMENTAL
General
Acrylamide (Fluka) was recrystallized from chloroform. Other reagents and solvents were of
commercial reagent grade and obtained from Merck, Fluka or Aldrich companies and used
without further purification. All products were characterized by comparison of their FT-IR
and NMR spectra and physical data with those reported in the literature. All yields refer to
the isolated products. Progress of reactions were followed by TLC on silica-gel Polygram
SILG/UV 254 plates or by GC on a Shimadzu model GC 10-A instrument with hydrogen
flame ionization detector. IR spectra were run on a Shimadzu FT-IR-8300 spectrophotometer.
NMR spectra were recorded on a Bruker Avance DPX instrument (250 MHz). The Pd analysis
and leaching test was carried out by ICP-OES analyzer (Varian, Vista-Pro). TEM analyses were
performed on a Philips model CM 10 instrument.
Preparation of the Supported Palladium Catalyst
The polymer supported palladium catalyst was prepared as described in our previous pa-
per21. The polymeric phosphinite ligand was obtained by transamidation reaction of
polyacrylamide (5% crosslinked with N,N′-methylene-bis-acrylamide) with hydroxylamine in
ethanol at 90–100 °C and its subsequent reaction with chlorodiphenylphosphine/Et3N
in THF at 0 °C. This polymeric ligand was complexed with Pd(OAc)2 to obtain the hetero-
geneous catalytic system. ICP analysis revealed that the catalyst contained an average of
0.15 mmol/g of Pd.
Sonogashira–Hagihara Coupling Reaction. General Procedure
A suspension of aryl halide (1.0 mmol), K2CO3 (2.0 mmol, 0.276 g), Pd complex (0.5–1 mole %,
0.033–0.067 g), tetrabutylammonium bromide (TBAB) (5 mole %, 0.016 g) and NMP (3 ml)
were mixed in a 10 ml round-bottomed flask and phenylacetylene (1.2 mmol, 0.122 g) was
added. The reaction mixture was stirred at 100 °C. Progress of the reaction was monitored
by TLC (or GC if necessary). On completion of the reaction, the mixture was filtered and
the filtrate poured into water (50 ml) and extracted with ethyl acetate (3 × 15 ml). Com-
bined organic phases were dried over Na2SO4, filtered and evaporated in vacuum. Products
were isolated by flash chromatography using petroleum ether, ethyl acetate, or their mixture
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Sonogashira Reaction Catalyzed by Supported Catalyst
1977
as eluents. Characterization of products was performed by comparison of their FT-IR,
1H NMR, 13C NMR, and physical data with those of the authentic samples.
Reuse of the Catalyst
When the Sonogashira reaction according to the procedure described above was finished,
the suspension was cooled down to room temperature and filtered off. The polymeric com-
plex was washed with NMP, water and acetone and dried under vacuum. It was then used in
the next reaction cycle with a new portion of reagents.
The authors gratefully acknowledge the partial support of this study by Shiraz University Research
Council.
REFERENCES AND NOTES
1. a) Miyaura N.: Cross-Coupling Reaction. Springer, Berlin 2002; b) Alonso F., Beletskaya
I. P., Yus M.: Chem. Rev. 2004, 104, 3079; c) Chinchilla R., Najera C.: Chem. Rev. 2007,
107, 874.
2. a) Sonogashira K. in: Comprehensive Organic Synthesis (B. M. Trost and I. Fleming, Eds);
and references therein. Pergamon, Oxford 1991; b) Bunz U. H. F.: Chem. Rev. 2000, 100,
1605.
3. Sonogashira K., Tohda Y., Hagihara N.: Tetrahedron Lett. 1975, 44, 44.
4. Thorand S., Krause N.: J. Org. Chem. 1998, 63, 8551.
5. a) Glaser C.: Ber. Dtsch. Chem. Ges. 1869, 2, 422; b) Li J.-H., Liang Y., Zhang X.-D.:
Tetrahedron 2005, 61, 1903; c) Li J.-H., Liang Y., Wang D.-P., Liu W.-J., Xie Y.-X., Yin
D.-L.: J. Org. Chem. 2005, 70, 2832; and references therein.
6. a) Fu X., Zhang S., Yin J., Schumacher D. P.: Tetrahedron Lett. 2002, 43, 6673; b) Cwik A.,
Hell Z., Figueras F.: Tetrahedron Lett. 2006, 47, 3023; c) Bakherad M., Keivanloo A.,
Bahramian B., Mihanparast S.: Tetrahedron Lett. 2009, 50, 6418.
7. a) Heuze K., Mery D., Gause D., Astruc D.: Chem. Commun. 2003, 2274; b) Yi C., Hua R.:
Catal. Commun. 2006, 7, 377; c) Komura K., Nakamura H., Sugi Y.: J. Mol. Catal. A:
Chem. 2008, 293, 72.
8. a) Bohm W. P. W., Herrmann W. A.: Eur. J. Org. Chem. 2000, 3679; b) Pal M.,
Parasuraman K., Gupta S., Yeleswarapu K. R.: Synlett 2002, 1976.
9. Gholap A. R., Venkatesan K., Pasricha R., Daniel T., Lahoti R. J., Sprinivasan K. V: J. Org.
Chem. 2005, 70, 4869.
10. a) Khalafi-Nezhad A., Panahi F.: Green Chem. 2011, 13, 2408; b) Firouzabadi H.,
Iranpoor N., Gholinejad M.: J. Mol. Catal. A: Chem. 2010, 321, 110; and references
therein.
11. a) Batey R. A., Shen M. A., Lough J.: Org. Lett. 2002, 4, 1411; b) Ma Y., Song C.,
Jiang W., Wu Q., Wang Y., Liu X., Andrus M. B.: Org. Lett. 2003, 5, 3317.
12. Cai M., Sha J., Xu Q.: Tetrahedron 2007, 63, 4642.
13. a) Kabalka G. W., Wang L., Namboodiri V., Pagni R. M.: Tetrahedron Lett. 2000, 41, 5151;
b) Liang Y., Xie Y.-X., Li J.-H.: J. Org. Chem. 2006, 71, 379.
14. Erdelyi M., Gogoll A.: J. Org. Chem. 2003, 68, 6431.
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 12, pp. 1967–1978

1978
Tamami, Ghasemi:
15. a) Chow H.-F., Wan C.-W., Low K.-H., Yeung Y.-Y.: J. Org. Chem. 2001, 66, 1910;
b) Uozumi Y., Kobayashi Y.: Heterocycles 2003, 59, 71.
16. a) Markert C., Bannwarth W.: Helv. Chim. Acta 2002, 85, 1877; b) Garcia-Bernabe A.,
Tzschucke C. C., Bannwarth W., Haag R.: Adv. Synth. Catal. 2005, 347, 1389; c) Lu N.,
Chen Y.-C., Chen W.-S., Chen T.-L., Wu S.-J.: J. Organomet. Chem. 2009, 694, 278.
17. a) Firouzabadi H., Iranpoor N., Gholinejad M., Hoseini J.: Adv. Synth. Catal. 2011, 353,
125; b) Firouzabadi H., Iranpoor N., Ghaderi A.: Org. Biomol. Chem. 2011, 9, 865.
18. Jiang J.-Z., Cai C.: J. Colloid Interface Sci. 2007, 307, 300.
19. Ye Z.-W., Yi W.-B.: J. Fluorine Chem. 2008, 129, 1124.
20. a) Tamami B., Mahdavi H.: React. Funct. Polym. 2005, 64, 179; b) Tamami B., Fadavi A.:
Catal. Commun. 2005, 6, 747; c) Tamami B., Ghasemi S.: J. Iran. Chem. Soc. 2008, 5, 26.
21. Tamami B., Ghasemi S.: J. Mol. Catal. A: Chem. 2010, 322, 98.
22. a) Iranpoor N., Firouzabadi H., Gholinejad M.: Can. J. Chem. 2006, 84, 1006; b) Iranpoor N.,
Firouzabadi H., Azadi R.: J. Organomet. Chem. 2008, 693, 2469.
23. a) Jeffery T.: Tetrahedron Lett. 1985, 26, 2667; b) Jeffery T.: Tetrahedron 1996, 52, 10113.
24. a) Leadbeater N. E., Tominack B. J.: Tetrahedron Lett. 2003, 44, 8653; b) Bandini M.,
Luque R., Budarin V., Macquarrie D. J.: Tetrahedron 2005, 61, 9860.
25. Nam T. S. P., Matthew V. D. S., Christopher W. J.: Adv. Synth. Catal. 2006, 348, 609.
26. In a typical experiment, Pd compelx (0.5 mole %, 0.033 g), iodobenzene (1.0 mmol,
0.204 g), phenylacetylene (1.2 mmol, 0.122 g), K2CO3 (2.0 mmol, 0.267 g), TBAB
(5 mole %, 0.016 g) and NMP (3 ml) were taken in a round-bottomed flask and stirred at
100 °C for 1 h. At this stage (25% conversion), the catalyst was filtered off and the
experiment was continued with the filtrate for another 24 h. There was no detectable
increase in the product concentration, as is evident from the GC analysis.
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 12, pp. 1967–1978