Synthesis of Pd(II) large dinuclear macrocyclic complex tethered through two dipyridine-bridged aza-crowns as an efficient copper- and phosphine-free Sonogashira catalytic reaction

Article abstract of DOI:10.1016/j.jorganchem.2018.04.009

For the first time the new 32-membered macrocyclic dinuclear palladium complex of two aza-crown macrocycles, bearing two pyridine arms, Pd₂L₂Cl₄ was synthesized and characterized by elemental analysis, IR, NMR spectroscopy and single crystal X-ray diffraction methods. Pd₂L₂Cl₄ was investigated as a moisture/air-stable catalyst for Sonogashira cross-coupling reaction in the absence of copper and phosphine ligand in DMSO. Thermal stability, possible occurrence of tandem reactions, promoted catalytic performance as well as synergistic effects are of advantageous features of Pd₂L₂Cl₄. By employing Taguchi method, optimum conditions (110 °C, 6 h, KOAc, 2 mol% cat.) were determined. Moreover, the homogenous catalyst represented good reusability up to four cycles. Comparing the catalytic activity of several other previously reported Pd(II) dinuclear complexes, Pd₂L₂Cl₄ enjoys the advantages of short time of reaction and thermal stability.

Full text of DOI:10.1016/j.jorganchem.2018.04.009

Accepted Manuscript
Synthesis of Pd(II) large dinuclear macrocyclic complex tethered through two
dipyridine-bridged aza-crowns as an efficient copper- and phosphine-free
Sonogashira catalytic reaction
Bahram Ghanbari, Leila Shahhoseini, Hadighehsadat Hosseini, Mojtaba
Bagherzadeh, Agata Owczarzak, Maciej Kubicki
PII:
S0022-328X(18)30239-0
10.1016/j.jorganchem.2018.04.009
JOM 20401
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 19 February 2018
Revised Date: 1 April 2018
Accepted Date: 8 April 2018
Please cite this article as: B. Ghanbari, L. Shahhoseini, H. Hosseini, M. Bagherzadeh, A. Owczarzak,
M. Kubicki, Synthesis of Pd(II) large dinuclear macrocyclic complex tethered through two dipyridine-
bridged aza-crowns as an efficient copper- and phosphine-free Sonogashira catalytic reaction, Journal
of Organometallic Chemistry (2018), doi: 10.1016/j.jorganchem.2018.04.009.
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ACCEPTED MANUSCRIPT
Synthesis of Pd(II) Large Dinuclear Macrocyclic Complex Tethered Through two
Dipyridine-Bridged aza-Crowns as an Efficient Copper- and Phosphine-Free Sonogashira
Catalytic Reaction
Bahram Ghanbari 1*, Leila Shahhoseini 1, Hadighehsadat Hosseini1, Mojtaba Bagherzadeh1, Agata
Owczarzak 2, Maciej Kubicki2
1. Department of Chemistry, Sharif University of Technology, Tehran, Iran, PO Box 11155- 3516
2. Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Pozna
ń, Poland
Abstract
For the first time the new 32-membered macrocyclic dinuclear palladium complex of two aza-crown
macrocycles, bearing two pyridine arms, Pd2L2Cl4 was synthesized and characterized by elemental
analysis, IR, NMR spectroscopy and single crystal X-ray diffraction methods. Pd2L2Cl4 was investigated
as a moisture/air-stable catalyst for Sonogashira cross-coupling reaction in the absence of copper and
phosphine ligand in DMSO. Thermal stability, possible occurrence of tandem reactions, promoted
catalytic performance as well as synergistic effects are of advantageous features of Pd2L2Cl4. By
employing Taguchi method, optimum conditions (110 °C, 6h, KOAc, 2 mol% cat.) were determined.
Moreover, the homogenous catalyst represented good reusability up to four cycles. Comparing the
catalytic activity of several other previously reported Pd(II) dinuclear complexes, Pd2L2Cl4 enjoys the
advantages of short time of reaction and thermal stability.
Keywords: dinuclear, macrocyclic, Sonogashira, palladium.
1. Introduction
Due to the applicability in the formation of carbon–carbon bonds, alkynylation via Sonogashira
cross-coupling is one of the key reactions in organic synthesis [1–4]. Moreover, Pd(II) complexes
are exceedingly effective and eminent catalysts applicable in the syntheses of the polyfunctional
alkynes by combination of the corresponding alkynes and aryl halides, whereby the development
[5–9]
of new catalysts is of vital research interest
.
Historically, Sonogashira employed [PdCl2(PPh3)2] for alkynylation reaction along with Cu(I)
[10]
salt as co-catalyst in the presence of diethylamine as base and solvent in inert atmosphere
.
The catalytic reaction suffers from two drawbacks. Firstly, the formation of a diyne due to the
oxidative coupling of terminal acetylene (also known as Glaser–Hay type reaction) resulted in
unwanted byproducts [11]. Again, owing to humidity and air sensitivity of phosphine ligands,
researchers are encouraged to look for new alternative ligands to eliminate the necessity for inert
condition in this catalytic reaction by developing copper- and phosphine-free Pd(II) catalysts [12–
21]
.
Development of macrocyclic dinuclear Pd(II) (MDP) complexes are of significant research
interests which had high contribution on development of new catalysts in modern synthetic
organic chemistry [20,22]. Basically, MDP catalysts enjoy from two main features as having two
metal cores and encompassing of the metal ions within the cyclic structure. From a mechanistic
point of view, the presence of two metal cores in MDP catalysts results in synergistic effects
which consecutively give rise to possible occurrence of tandem reactions [23]. Hence, these
catalysts exhibit better catalytic activity and selectivity together with higher efficiencies in
comparison with corresponding monometallic catalysts [24]. Another distinctive feature of MDP
catalysts is their thermal stability which leads to the catalytic reactions at temperatures above
100°C.
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The coordination chemistry of bridging ligands anchored with pyridine side arms has been
shown to have prominent complex ability towards transition metal ions, leading to the formation
of coordination polymers [25,26], coordination spheres [27–29], notable collection of macrocycles as
well as interlocked molecules potentially applicable in formation of molecular machines [30]. In
1993, Fujita reported bis(4-pyridyl)-substituted ligands as new flexible dinuclear macrocyclic
ligands to form cis-enthylenediamine Pd(II) complexes [31]. Later, he also published several
reports on a group of functional macrocyclic complexes [32,33]. Since pyridine and pyrimidine
moieties demonstrated appropriate complexation properties for Pd(II) cation, they were reputed
as the suitable catalytic candidates for Sonogashira coupling reactions. In the meantime, the
dipyrimidyl-Pd(II) complexes were employed in the copper-free coupling of different
halobenzene with phenylacetylene using N-butylamine as base in THF solvent at 65 °C [34]
.
Recently, we reported [35] the synthesis of a tecton L (Scheme 1) constructed from aza-crown
macrocycle decorated with two pyridine side arms, capable to yield several new 1D coordination
polymers (CPs) with Mn(II), Ni(II), Cu(II), Cd(II) and Pb(II) cations.
Scheme 1 is here
In the course of preparation more new CPs, however, we strikingly found that L was capable to
produce a new MDP in the presence of Pd(II) (Scheme 1), instead. To the best of our knowledge,
no report on the synthesis nor catalytic activity of MDP complexes cyclized through aza-crown
macrocycle linkers has been reported before. Thus, we undertook the synthesis, full
characterization and catalytic activity of the new large 32-membered MDP complex, Pd2L2Cl4,
comprising two aza-crown macrocycles bearing two pyridine linkers, coordinating Pd(II) in the
trans form (Scheme 1).
2. Results and discussion
2.1. Syntheses and characterizations
The macrocyclic ligand L was synthesized[35] through the reaction of the precursor macrocycle 1
with two equivalents of 4-(chloromethyl) pyridine hydrochloride in the present of potassium
carbonate and potassium iodide in DMF as solvent (Scheme 1). The purity of the sample was
checked by employing 1H and 13C{1H}NMR spectroscopy (Fig. S1).
The dinuclear complex, Pd2L2Cl4, was quantitatively prepared by admixing of L and
bis(acetonitrile) dichloropalladium(II) in DMF (see also Scheme 1).
2.2. Single Crystal X-ray Diffraction Studies
Some appropriate crystals of Pd2L2Cl4 applicable in X-ray crystallography were obtained by
slow layering of L on DMF solution of bis(acetonitrile)dichloropalladium(II) complex without
stirring and keeping the solution at room temperature for several days. Some selected
crystallographic data for Pd2L2Cl4 complex were summarized in Table S1.
The molecular structure of Pd2L2Cl4 was shown in Figure 1, together with the pertinent atomic
notations.
Figure 1 is here
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The dimeric complex molecule is Ci-symmetrical (it lies across the inversion center in the space
group P21/n); in consequence, the asymmetric unit for Pd2L2Cl4 encompasses one macrocyclic
ligand (L), two Cl atoms and one Pd(II) center together with three DMF molecules (Figure 1b).
Table S1 and Figure 1b show some selected bond lengths and angles for Pd2L2Cl4 complex. The
crystal structure of Pd2L2Cl4 exhibited a dinuclear architecture, resembling a rhombus having
two Pd(II) centers on each parallel sides, whereby bridged via two flexible L units. Pd atoms
were coordinated with two nitrogen donors of the pyridyl side arms on L alongside two chlorine
atoms that brought about a square planar geometry about the Pd(II) metal center (see also the
bond angles for the abovementioned square planer geometry in Table S2). The resulted Pd2L2Cl4
complex demonstrated a trans stereochemistry, i.e. trans-[Pd2(µ-L)2Cl4] Meanwhile, the
macrocycle moieties on Pd2L2Cl4 accepted drawn-out chair conformations. The molecular
dimensions of Pd2L2Cl4 were ~13.7 × 5.6 Å, whereas two Pd(II) atoms were separated from each
other by ~5.41Å. Three molecules of DMF were situated on one side of the aromatic ring (Figure
S2) and connected through CH…O type hydrogen bonding interactions between C(10)−H(10A),
C(27)−H(27) of Pd2L2Cl4 and O(1A), O(1B) of DMF with a distance of 2.56, 2.48 Å (Table S3).
Additionally, C−H…Cg (π ring) interactions are perceptible between C(1C)−H(1C) of DMF and
Cg(3) of Pd2L2Cl4 through a distance of 2.93 Å (Figure S2). Moreover, some selected weak
interaction data were collected in Table S3.
2.3. Thermal experiments and FTIR spectra of Pd2L2Cl4
Thermogravimetric behavior of Pd2L2Cl4 complex was surveyed under a nitrogen atmosphere in
the temperature range of 25-900°C. TGA and DTGA curves are exhibited in Figure S3.
Figure S3 addressed a typical weight loss up to 1.5% at ∼200 °C, corresponding to the
evaporation of the entrapped solvent molecules within the crystal structure. Immediately,
Pd2L2Cl4 commenced to decompose at about >225 °C and continuously lose weight to achieve
balance at 744°C. As a final point, amount of the residual was found ~15% corresponding to 2
mol of Pd per one mole of Pd2L2Cl4.
The FTIR spectra of L and Pd2L2Cl4 complex were run in the spectral range of 400-4000 cm-1.
The spectra accompanied by the probable assignments for the main bands belong to various
functional groups were shown in Figure 2.
Figure 2 is here
In the spectra, weaker bands at 2850-3000 cm-1 were assigned to sp3 C–H bond stretching
modes, whereas the respective band at 3050 cm-1 was attributed to sp2 C-H stretching.
Meanwhile, the band at ~1412 cm-1 was assigned to the stretching vibration of the pyridine ring
[36]
in ligand L, wherein this band was shifted to 1443 cm-1 in the Pd2L2Cl4 comparing to L
[37,38]
spectra (Figure 2). The ring breathing band of the pyridine moieties
was found at shifted
from ~991 cm-1 in L to the above mentioned band in Pd2L2Cl4. Moreover, thanks to the
coordination of Pd(II) with pyridine side arms, the C=C and C=N bonds shifted from 1595 cm-1
[39]
in L to new bands at 1610 and 1662 cm-1. Owing to coordination of Pd(II) with N atoms of
pyridine ring in Pd2L2Cl4 determined by single crystal X-ray diffraction, it would be reasonable
to assume that the observed blue shift in the stretching vibration of the pyridine ring from 1412
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(in L) to 1443 cm-1 (Pd2L2Cl4) was another supportive indication on the coordination of Pd(II)
with the pyridine moieties in L.
2.4. 1H NMR study of Pd2L2Cl4 in DMSO-d6
The 1H NMR spectra of Pd2L2Cl4 and L were displayed in Figure 3 alongside the assignment of
the protons in L.
Figure 3 is here
The aliphatic region of the spectrum exhibited five signals, three of which were composed of
singlets (at 3.48 ppm for Hc, 3.56 ppm for Hd and 4.39 ppm for He) and the other two signals
were a triplet at 2.42 ppm and a quintet 1.59 ppm assigned to Hb and Ha, respectively. Moreover,
the other five signals were assigned to the aromatic protons at 6.9 ppm for Hh, 7.1 ppm for Hj,
7.22 ppm for Hg, 7.26 ppm for Hi and 8.43 ppm for Hf in DMSO-d6. Comparing remarkable
downfield chemical shifts for the protons in Pd2L2Cl4 with the parent free ligand indicated on the
stability of Pd2L2Cl4 in the DMSO (Table 1).
Table 1 is here
Some practical features of Pd2L2Cl4 as air/moisture and thermal stability together with potential
existence of promoted synergistic effects and possible occurrence of tandem reactions for N-
[40]
donor pyridine ligands
as well as the large ring system encouraged us to explore the
employment of Pd2L2Cl4 in popular Sonogashira catalytic cross-coupling reaction.
2.5. Catalytic activity
Hereinafter, the study on catalytic activity of Pd2L2Cl4 in Sonogashira coupling reaction were
executed under phosphine- and copper-free and aerobic condition, owing to the rich chemistry of
Pd(II) complexes. For this purpose, the copper-free catalytic reaction of iodo benzene (0.6
equiv.) with phenyl acetylene (1 equiv.) was employed as the model reaction. DMSO was
employed as the solvent because of the solubility of the reaction components as well as its high
boiling point. Primarily, in order to determine the optimum reaction conditions for the synthesis
of 1,2-diphenyl acetylene, the impacts of various parameters (e.g., type of the solvent and base as
well as the reaction time) were considered. The results for choosing of appropriate solvent
alongside with the reaction time in this reaction were summarized in Table 2.
Table 2 is here
A series of the experiments were proceeded to assess the effect of some common bases viz.
KOAc, NaOAc, KOH and NEt3. The results together with the catalyst amount were tabulated in
Table 3, whereas the best efficiency was found for KOAc.
Table 3 is here
2.5.1. Determination of the optimal conditions by using Taguchi method
In order to acquire sufficient and pertinent data to understand the science behind a scientific
phenomenon, Taguchi has established a technique based on "orthogonal arrays" experiments. By
employing this method to engineering experiments [41], the number of "variance" in the process
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could be considerably reduced, giving rise to reducing the number of the experiments needed to
attain "optimum settings" for critical parameters.
Herein, we applied the Taguchi approach to optimize conditions and to select the most influential
parameters on conversion of the phenylacetylene to diphenylacetylene. In our experiments,
Taguchi’s orthogonal array table was set up by choosing four parameters at three levels for each
of them (Table S4).
By this condition, the number of arrangements will be 34=81, whereby employing Taguchi
method the number of the required experiments is reduces to nine. The Taguchi’s L9 design
together with the results for the corresponding measurements were summarized in Table S5
(each experiment was repetitively performed three times).
One of the most important parameters is S/N ratio in Taguchi method (see also Table S5) in
which S (signal) and N (noise) signify the desirable and undesirable characteristic output values,
respectively. Although, the S/N ratios in Table S5 are different according to the type of
characteristics, but the greater S/N ratio is the more desirable one. In the case that bigger
characteristics are required, the S/N ratio is defined by the Eq (1).[42]
ꢊ
ꢂ
∑
ꢄ
ꢉ
ꢇ
ꢈ
ꢅ
ꢆꢋꢌ
ꢀ
ꢆ
= −10 logꢂꢃ[
]
Eq (1)
ꢁ
ꢍ
In the Eq (1), yi signifies the result of the experiment and n is the replication number of the
experiment. Table S5 represents the S/N ratio for diphenylacetylene conversion calculated by
using Eq. (1).
Table S6 presented the mean S/N ratio calculated for each level of the parameters as well as the
relative significance of each parameter which was shown in the last column of Table S6.
Moreover, Figure S4 exhibits the S/N response graph for diphenyl acetylene conversion.
The best operational settings for this catalytic reaction were found corresponding to A3, B3, C3
and D2 levels in Table S6. Accordingly, the best S/N ratio exhibited in Figure S4 established the
optimal conditions as follow: the best temperature (A at level 3), catalyst content (B at level 3),
the shortest reaction time (C at level 3) and the most efficient base (D at level 2) were 110 °C, 2
mol%, 8 h and KOAc, respectively. Incidentally, the reaction proceeding at temperatures above
110 °C makes the catalyst susceptible to solvolysis process and/or solvent decomposition,
though, the reaction conversion was close to 100% at this temperature. In case of the reaction
time, since >99% yields were obtained for the reaction times of 6 (C at level 2) and 8 (C at level
3) hours, the former reaction time was selected. Likewise, the catalyst value 2 mol% was chosen
because of the conversion >99%.
2.5.2. Substrate scope for the Sonogashira cross-coupling reaction
In order to evaluate the applicability of Pd2L2Cl4 in Sonogashira cross coupling reaction, the
optimized conditions (i.e. with 2 mol% Pd2L2Cl4, aryl halides (0.6 mmol), phenyl acetylene (1
mmol), KOAc (1.5 mmol), T = 110 °C, t = 6h and solvent = DMSO) were employed in the cross
coupling reaction of phenyl acetylene with a number of aryl halides represented in Table 4
(entries 1–6).
Table 4 is here
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The experimental results in Table 4 disclosed that the reaction of aryl bromide containing
electron withdrawing substituents such as acetyl group (Table 4, entry 3 and 4) afforded the
corresponding coupled products in high yields (based on GC yield). Furthermore, the employing
1-bromo naphthalene led to good reaction yield compared to aryl bromide (Table 4, entry 5 and
3). In the course of these experiments, aryl iodide exhibited much more reactivity than the
corresponding aryl bromide (Table 4, entry 5 and 3). Meanwhile, the dinitro-substituted aryl
chloride exhibited better reaction yield than aryl bromide (Table 4, entry 3 and 6). The catalytic
reaction represented far better yield in the case of benzyl chloride (Table 4, entry 2).
The probability of Glaser homocoupling reactions was checked by applying phenyl acetylene as
the only reagent in the catalytic reaction (see Table 4, entry 7), wherein no homocoupling
product was obtained [43]. From the mechanistic point of view, Sonogashira reaction is generally
involved in the formation of a Pd(0) species (e.g., by reductive elimination of the product from
an Ar−Pd−C≡C−Ar´ intermediate) prior to the subsequent oxidative addition of Ar−X,
regenerating Pd(II) species which is the key step in the catalytic cycle [44]
.
2.5.3. Reusability
The reusability of Pd2L2Cl4 as the catalyst was explored and the results were summarized in
Figure S5.
As evident from Figure S5, the accomplishment of the first cycle resulted 99% yield of the
corresponding product while the yield was decreased progressively in subsequent cycles to 96%,
80% and finally 58% (Figure S5). More experimental studies are required in future to immobilize
Pd2L2Cl4 on the surface of a catalytic support to improve the reusability of the catalyst.
2.6. Comparison of Pd2L2Cl4 with the other MDP catalysts
[20,45–55]
There are several reports
in the literatures on the catalytic activity of the other MDP
complexes in coupling reactions. Some of these examples are comparable with Pd2L2Cl4 in terms
of the overall yield as well as the reaction conditions in Table S7.
In order to explain the scope of Pd2L2Cl4 application in catalytic cross-coupling reactions,
several examples of MDP complexes are given in the Table S7. Considering Sonogashira cross-
coupling reaction, Pd2L2Cl4 exhibited higher yield of the product alongside with less reaction
time, comparing with the complexes in the entries 13 and 14 in Table S7. Pd2L2Cl4 was also
superior to complex 11 in Table S7 regarding the time of reaction.
Some practical features of Pd2L2Cl4 as air/moisture, thermal stability, good catalytic
performance, promoted synergistic effects and possible occurrence of tandem reactions were
attributed to the presence of N-donor pyridine ligands [40] as well as the large ring system.
3. Experimental
3.1. Materials and instrumentations
The chemicals applied in this work were purchased from commercial suppliers. IR spectra were
recorded on a FT-IR ABB Bomem MB-100 as KBr disks within the range of 400-4000 cm-1.
Thermogravimetric measurements were executed through thermogravimetry runs at a
1
temperature ramp of 10 °C min− up to 900°C under a continuous flow of dry nitrogen. The
thermal analysis instrument was a METTLER/TOLEDO in the TG mode. Gas chromatography
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(GC) analyses were accomplished on an Agilent Technologies 6890N, equipped with a 19, 019
J-413 HP-5, 5% phenyl methyl siloxane, capillary column (60.0 m ×250 µm × 1.00 µm). 1H and
13C NMR spectra were run in CDCl3 and DMSO-d6 at room temperature on a Bruker-ARX500
instrument.
Diffraction data were collected at 120 (1) K, by the ω-scan technique on Agilent Technologies
Xcalibur four-circle diffractometer with Eos CCD detector and graphite-monochromated MoKα
radiation (λ=0.71069 Å). The data were corrected for Lorentz-polarization as well as for
absorption effects. The structures were resolved with SHELXT-2013 and refined with the full-
matrix least-squares procedure on F2 by SHELXL-2013. All non-hydrogen atoms were refined
anisotropically, all hydrogen atoms were placed in idealized positions and refined as ‘riding
model’ with isotropic displacement parameters set at 1.2 (1.5 for methyl groups) times Ueq of
appropriate carrier atoms. Analysis of the structure and presentation of the results were carried
out by PLATON software. Crystallographic data (excluding structure factors) for the structural
analysis has been deposited with the Cambridge Crystallographic Data Centre, Nos. CCDC
1542745 (Pd2L2Cl4·6DMF).
3.2. Synthesis of the precursor dialdehyde, 1 and L
The precursor dialdehyde as well as the macrocycle 1 were prepared according to the procedure
illustrated in Scheme 1, employing previous reports [56,57]. The diaza-crown macrocycle bearing
pyridine unit, L was also synthesized by employing a new method that was less complicated
(Scheme 1) than the recently reported method [35] as follow: the parent macrocycle 1 (1.00 g) was
dissolve in DMF (10 cm3), potassium carbonate (1.12 g) and potassium iodide (0.03 g) was
added to the above solution. By stirring the mixture in the presence of 4-chloromethyl pyridine
hydrochloride (0.5 g) for one week under N2 atmosphere (without heating), a cream-colored
precipitate was obtained after adding water (300 cm3). The solid was filtered and washed with
distilled water prior to drying in air. The product was purified by recrystallization from
acetonitrile. Yield: 35 mg, 57%, Anal. Calc. for C31H34N4O2: C, 75.28; H, 6.93; N, 11.33. Found:
C, 75.4; H, 6.9; N, 11.2%. m. p. 165°C.
1H NMR (500 MHz, CDCl3, TMS) δ (ppm):1.64 (q, 2H, NCH2CH2CH2N); 2.56 (t, 4H,
NCH2CH2CH2N); 3.49, 3.63 (s, 8H, ArCH2, CH2C5H4N); 4.38 (s, 4H, OCH2CH2O); 6.90-
6.93,7.08-7.10, 7.25-7.28 (m, 8H, C6H4); 7.19, 8.47 (8H, C5H4N).
13C NMR (500 MHz, CDC13, TMS) δ (ppm): 24.55 (NCH2CH2CH2N); 51.19
(NCH2CH2CH2N); 52.73 (CH2C5H4N); 56.53 (ArCH2); 66.27 (OCH2CH2O); 110.73, 120.31,
123.59, 125.98, 128.58, 132.57, 149.52, 150.01, 157.19 (C6H4, C5H4N).
FT-IR (KBr, cm-1) bands: 2798-3065 (m), 1595 (s), 1491 (s), 1445 (s),1412(w), 1373 (w),
1339(w), 1290(w), 1232(s), 1114(m), 1053(m), 990 (w), 936 (s), 835(w), 803(w), 763 (s), 616
(m), 489 (m).
3.3. Preparation of the dinuclearPd(II) complex
Bis(acetonitrile)dichloropalladium(II) was prepared by recrystallization of Pd(II) chloride in
acetonitrile. Layering of a DMF solution (1 mL) of L (50 mg, 0.100 mmol) over an DMF
solution (0.5 mL) of bis(acetonitrile)dichloropalladium(II) (16.5 mg, 0.130 mmol) in narrow tube
7

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in room temperature for 1 weak, resulted single crystals of Pd2L2Cl4. Yield: 40.8%. Elemental
analysis (%) calculated for C62H68Cl4N8O4Pd2, 6(C3H7NO) (1115.141g/mol): C, 66.78, H, 6.15,
N, 10.05; found C, 66.7, H, 5.93, N, 10.1.
1H NMR (500 MHz, DMSO-d6, TMS) δ (ppm): 1.70 (q, 2H, NCH2CH2CH2N); 3.58, 3.72 (s, 8H,
ArCH2, CH2C5H4N); 4.40 (s, 4H, OCH2CH2O); 6.96, 7.29, 7.32 (m, 8H, C6H4); 7.13, 8.80 (8H,
C5H4N).
13C NMR. The acquisition of the spectra was unsuccessful due to insufficient solubility of
Pd2L2Cl4 in any deuterated solvent.
FT-IR (KBr, cm-1) bands: 2801-3027 (m), 1602(s), 1610 (s), 1495 (s), 1443 (s), 1378 (w),
1237(s), 1112 (m), 1057 (m), 936 (m), 814(w), 753 (s),615 (w), 508 (w).
3.4. General procedure for the Sonogashira cross-coupling reaction
A solution of phenyl acetylene (0.5 mmol), aryl halide (0.3 mmol), Pd2L2Cl4 (2 mol%), 2 mL
solvent and 1.5 mmol base was mixed and stirred under air atmosphere at 110°C for the fixed
time. During the reaction proceeding, the consumption of starting material was checked by TLC.
After elapsing of the chosen time, water (2 mL) was added to the reaction mixture, extracted
with ethyl acetate (2 × 5 mL) (products and starting materials are soluble in ethyl acetate), dried
over MgSO4, and injected to the GC chromatography. All of compounds have been characterized
by 1H NMR spectra (Figure S3).
3.5. Reusability test
0.6 mmol iodo benzene was charged into a reaction vessel together with 1 mmol phenyl
acetylene and 3 mmol KOAc in DMSO (2 ml). 2 mol% of Pd2L2Cl4 was added to the
abovementioned mixture at 110 °C. After 6 h the mixture was cooled to room temperature,
wherein enough water was delivered to the flask to form a biphasic mixture for extraction with
ethyl acetate (2 mL) for three times. After collecting of the organic phase aliquots (ethyl acetate),
they were sampling for injection to the GC chromatography for more analysis. In order to
recover, the remaining phase of the previous step, aqueous solution (DMSO+water) was washed
with ethyl acetate for several times to accomplish thorough removal of the products as well as
starting materials. The extracted DMSO solution was checked with GC chromatography to
monitor the presence of any unreacted starting material. Finally, the aforesaid solution
(DMSO+water) was evaporated and the remaining catalyst utilized as the next catalytic cycle
under the same reaction conditions.
4. Conclusions
We successfully prepared and characterized a new dinuclear Pd(II) complex with pyridine-based
aza-crown macrocyclic ligand. The X-ray analysis endorsed the presence of large macrocyclic
structure for Pd2L2Cl4 complex. Diagnosis of the complex by TGA reserved typical thermal
stability up to 200 °C, whereas the application of Pd2L2Cl4 in solution as a catalyst was
permitted. Moreover, 1H NMR and FTIR spectra concisely exhibited the persistence of the solid
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state structure in DMSO-d6. Thus, the complex showed strong performance as copper- and
phosphine-free Sonogashira cross coupling reaction in aerobic condition between aryl halides
and phenyl acetylene in DMSO. Pd2L2Cl4 unveiled much better catalytic performance in
Sonogashira cross-coupling reactions than several other previously reported Pd(II) dinuclear
complexes which is attributed to the presence of N-donor ligands alongside with having the large
ring system in the complex.
Acknowledgement
This work was supported by Research Office of Sharif University of Technology.
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Tables
Table 1. 1H NMR chemical shift assignments (δ in ppm) together with ∆δ for the L and Pd2L2Cl4 and their displacement in
DMSO-d6 at 25oC.
Ha
Hb
Hc
Hd
3.56
3.72
0.16
80
He
4.39
4.40
0.01
5
Hh
6.90
6.96
0.06
30
Hi
Hj
Hg
7.22
7.32
0.10
50
Hf
L
1.59
1.70
0.11
55
2.42
3.48
3.58
0.08
40
7.26
7.29
0.03
15
7.10
7.13
0.03
15
8.43
8.80
0.37
185
Pd2L2Cl4
∆δ(ppm)
∆δ (Hz)
-
-
-
Table 2. The effect of time and solvent in Sonogashira cross coupling
reaction.
GC yield(%)
6h 12h
Entry
Solvent
3h
24h
2
-
-
1
2
3
DMSO/H2O
DMSO
-
60
-
-
>99
-
-
100
-
H2O
11

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Table 3. Effect of common base and catalyst amount in Sonogashira cross
coupling iodo benzene (0.6 mmol), phenyl acetylene (1 mmol), base (3 mmol), T
= 110 °C and solvent: DMSO.
GC yield(%)
Entry
base
cat. amount
(mmol)
3h
6h
1
2
3
4
5
KOAc
NaOAc
KOH
NEt3
KOAc
60
50
63
40
75
>99
95
80
87
>99
0.01
0.01
0.01
0.01
0.02
Table 4. Sonogashira coupling reaction conditions of some aryl
halides with phenyl acetylene in the presence of Pd2L2Cl4.
Entry
1
substrate
GC yield %
>99
2
100
3
4
20
80
5
48
6
7
96
0
12

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Scheme 1. The synthetic route for the preparation of L and Pd2L2Cl4 complex.

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Figure 1. (a) The X-ray crystal structure of Pd2L2Cl4, the solvent molecules are omitted for simplicity; (b) asymmetric unit
of the complex; (thermal ellipsoid plot at 30%).

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(a)
(b)
Pd2L2Cl4
L
-1
Wavenumber cm
Figure 2. (a) FTIR spectra of L and the Pd2L2Cl4 complex; (b) expanded region of the stretching vibrations of the
complexed pyridine covering its band shifts to higher wavenumbers.
f
f
(1)
(2)
Figure 3. 1H NMR spectra of L (top) and Pd2L2Cl4 (bottom) (ca. 2×10–2 M) in DMSO-d6 at 25oC.

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Highlights
•
•
•
•
•
A new large dinuclear macrocyclic Pd(II) complex was synthesized.
The linker was made from aza-crown macrocycle bearing two pyridine moieties.
The TGA exhibited thermal stability up to 200 °C.
The complex showed strong performance as Sonogashira cross-coupling catalyst.
The catalyst was moisture/air-stable, copper and phosphine free.