Palladium (II)–Salan Complexes as Catalysts for Suzuki–Miyaura C–C Cross-Coupling in Water and Air. Effect of the Various Bridging Units within the Diamine Moieties on the Catalytic Performance

Article abstract of DOI:10.3390/molecules25173993

Water-soluble salan ligands were synthesized by hydrogenation and subsequent sulfonation of salens (N,N’-bis(slicylidene)ethylenediamine and analogues) with various bridging units (linkers) connecting the nitrogen atoms. Pd (II) complexes were obtained in reactions of sulfosalans and [PdCl₄]^2?. Characterization of the ligands and complexes included extensive X-ray diffraction studies, too. The Pd (II) complexes proved highly active catalysts of the Suzuki–Miyaura reaction of aryl halides and arylboronic acid derivatives at 80 ^?C in water and air. A comparative study of the Pd (II)–sulfosalan catalysts showed that the catalytic activity largely increased with increasing linker length and with increasing steric congestion around the N donor atoms of the ligands; the highest specific activity was 40,000 (mol substrate) (mol catalyst × h)^?1. The substrate scope was explored with the use of the two most active catalysts, containing 1,4-butylene and 1,2-diphenylethylene linkers, respectively.

Full text of DOI:10.3390/molecules25173993

molecules
Article
Palladium (II)–Salan Complexes as Catalysts for
Suzuki–Miyaura C–C Cross-Coupling in Water and
Air. Effect of the Various Bridging Units within the
Diamine Moieties on the Catalytic Performance
Szilvia Bunda 1,2, Krisztina Voronova 3, Ágnes Kathó 1, Antal Udvardy 1,
*
and Ferenc Joó 1,4,
*
1
Department of Physical Chemistry, University of Debrecen, P.O. Box 400, H-4002 Debrecen, Hungary;
bunda.szilvia@science.unideb.hu (S.B.); katho.agnes@science.unideb.hu (Á.K.)
Doctoral School of Chemistry, University of Debrecen, P.O. Box 400, H-4002 Debrecen, Hungary
Department of Chemistry, University of Nevada, Reno, Reno, NV 89557, USA; kvoronova@unr.edu
MTA-DE Redox and Homogeneous Catalytic Reaction Mechanisms Research Group, P.O. Box 400,
H-4002 Debrecen, Hungary
2
3
4
*
Correspondence: udvardya@unideb.hu (A.U.); joo.ferenc@science.unideb.hu (F.J.)
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 3 August 2020; Accepted: 31 August 2020; Published: 2 September 2020
Abstract: Water-soluble salan ligands were synthesized by hydrogenation and subsequent sulfonation
of salens (N,N’-bis(slicylidene)ethylenediamine and analogues) with various bridging units (linkers)
connecting the nitrogen atoms. Pd (II) complexes were obtained in reactions of sulfosalans and
[PdCl4]2−. Characterization of the ligands and complexes included extensive X-ray diffraction studies,
too. The Pd (II) complexes proved highly active catalysts of the Suzuki–Miyaura reaction of aryl
halides and arylboronic acid derivatives at 80 ◦C in water and air. A comparative study of the Pd
(II)–sulfosalan catalysts showed that the catalytic activity largely increased with increasing linker
length and with increasing steric congestion around the N donor atoms of the ligands; the highest
specific activity was 40,000 (mol substrate) (mol catalyst
with the use of the two most active catalysts, containing 1,4-butylene and 1,2-diphenylethylene
linkers, respectively.
×
h)−1. The substrate scope was explored
Keywords: catalysis in water; C–C cross-coupling; Suzuki–Miyaura reaction; palladium;
sulfonated salan
1. Introduction
Salen (N,N’-bis(salicylaldiminato)-1,2-diaminoethane) and its derivatives, which can be easily
obtained by condensation of salicylaldehyde and ethylendiamine or their various substituted analogues,
have played prominent roles as ligands in coordination chemistry and catalysis throughout the
years [
salen, usually obtained from the latter by reduction with NaBH4 [
via Mannich reaction is also known [10]. Salan has become a general name for analogous
N,N’-bis(o-hydroxybenzyl)- -diaminoalkanes, too, which may have diverse linker groups between
1–
5]. Salan (N,N’-bis(o-hydroxybenzyl)-1,2-diaminoethane) is the tetrahydro derivative of
1,6–9]; however, direct synthesis
α,ω
nitrogen atoms and/or variously substituted o-hydroxybenzyl moieties. As secondary amines, salans are
much less vulnerable to hydrolysis than their diimine parent compounds, and for this reason, they are
more suitable for applications in aqueous media [11
have earned important applications in catalysis of various reactions such as polymerization [13
sulfoxidation [15], oxygen transfer [ ], fluorination and hydroxylation [16], to name a few. The promising
biomedical and catalytic properties and applications of salan complexes have been reviewed recently [ ].
,
12]. Transition metal complexes of salans
,
14],
9
1
Molecules 2020, 25, 3993; doi:10.3390/molecules25173993
www.mdpi.com/journal/molecules

Molecules 2020, 25, 3993
2 of 21
Carbon–carbon cross-coupling reactions are of fundamental importance in organic synthesis as
shown by the high number of publications (413 for the Suzuki–Miyaura reaction in 2019 (Scopus,
Elsevier)) and can be conveniently practiced in fully organic media [17–19]. On the other hand,
health and environmental safety requires the elimination of organic solvents from chemical processes
as much as possible. A viable alternative to the use of organic solvents is the application of water as the
reaction medium [20
chemistry, and this approach has been extended to the field of C–C cross-couplings, too [23
the replacement of volatile and harmful organic solvents but also improved process characteristics
–22]. Organometallic catalysis in aqueous systems has great potential for green
–29]. Not only
(fire safety, catalyst recycling, etc.) and product quality are attractive features of aqueous procedures.
In homogeneously catalysed aqueous/organic biphasic reactions, such as the Pd-catalysed
cross-coupling of aryl halides and arylboronic acids, the catalyst should be preferentially soluble in
water. Hydrophilic palladacycles [30], complexes of tertiary phosphines [23 31 32], N-heterocyclic
carbenes [33 35] and water-soluble complexes with salen ligands [ 36 37] have already been applied
as catalysts in aqueous C–C cross-couplings. Alternatively, the reactants and the catalyst have to be
,
,
–
2
,
,
incorporated into micelles formed by appropriate surfactants within the bulk aqueous phase [38
Both methods allowed the design of outstandingly productive and robust catalytic procedures.
–42].
We have been interested in aqueous organometallic catalysis for several years [21] and employed
as catalysts complexes of transition metals with water-soluble tertiary phosphine and/or N-heterocyclic
carbene ligands. Recently, we launched a program to study in aqueous media the catalytic properties
of sulfonated salan-based complexes in reactions such as hydrogenation of alkenes and ketones [43],
redox isomerization of allylic alcohols [44,45] and carbon–carbon cross-coupling reactions [46].
In particular, some Pd (II)–salan complexes were found to be highly effective catalysts for the
Sonogashira and the Suzuki–Miyaura cross-coupling reactions [46,47].
In contrast to what may be suggested by the simplified formulae in Scheme 1, the structure of
even the simplest sulfosalan, HSS (1), deviates from planarity and the free rotation around the C–N
bonds gives high flexibility to the ligands in coordination to a metal ion. This flexibility is largely
influenced by the length of the bridging unit between the secondary amine nitrogens (e.g., C2 vs
C4 alkyl chains). The structure, rigidity and steric requirements of the linker unit (e.g., ethyl, cis- or
trans-1,2-cyclohexyl, 1,2-diphenylethyl linkers) similarly may have large effects on the coordination
ability of the sulfosalan ligands, which may be manifested also in the catalytic properties of the
resulting complexes. During our studies, we noted important differences in the catalytic activities of
Pd (II)–sulfosalan complexes; therefore, we decided to perform a comparative study of a reasonably
large series of such complexes. In this paper, we present the results of a comparative study of the
catalytic performance of complexes
For the purpose of these studies, we synthesized the new ligands
Na2[Pd(PrHSS)] ( ), Na2[Pd(dPhHSS)] ( ), Na2[Pd(trans-CyHSS)] (10b) and Na2[Pd(cis-CyHSS)] (10c).
6
–
10 (Scheme 1) in Suzuki–Miyaura cross-coupling reactions.
4,
5b and 5c and the new complexes
7
9
To gain more insight into the structural features of the sulfosalan ligands and their Pd (II)–complexes,
all sulfosalan ligands, 1–5, as well as complexes 6 and 7 were studied in detail by single crystal X-ray
diffraction (SC-XRD) (1 and 3 by powder X-ray diffraction, too).

Molecules 2020, 25, 3993
3 of 21
Scheme 1. Salan ligands (hydrogenated sulfonated salens,
1–5
) and their Pd (II) complexes (6–10) used
in this study, together with the intermediates of their synthesis (salens 11
–
15 and hydrogenated salens
21–25): ligands 1–5 were isolated as zwitterions, and complexes 6–10 were isolated as Na salts.
2. Results and Discussion
2.1. Synthesis
The new ligands,
4
,
5b and 5c, and the Pd (II) complexes
7
,
9
,
10b and 10c, were synthesized
and 10a 44 47].
according to the procedure used by us earlier for the rest of the compounds,
1–
3,
6
,
8
[
–
Briefly, the starting salens were obtained by condensation of salicylaldehyde and the appropriate
diamine, and the latter were reduced to the hydrogenated salens with four equivalents of NaBH4
in methanol. The white hydrogenated salen products were sulfonated in an ice-cold 4:1 mixture of
fuming sulfuric acid (20%) and concentrated (96%) sulfuric acid. Addition of the reaction mixtures to
cold water and adjustment of the pH to 4 led to formation of white precipitates of the salan ligands
(Figure 1).
Figure 1. Capped sticks representations of 1 × 2H2O. Symmetry code: (i) –x, 1–y, –z.
Na2[Pd(PrHSS)] (7), Na2[Pd(dPhHSS)] (9) and Na2[Pd(CyHSS)] (10) were prepared from
equivalent amounts of the sulfosalan ligand and (NH4)2[PdCl4] in aqueous solutions adjusted to pH 7.5
with concentrated NaOH solution and kept at 60 ◦C for 10 h. The yellow complexes were precipitated
from the cooled reaction mixtures with the addition of ice-cold ethanol.
All compounds showed the characteristic A1 sulfonate stretching frequency in the infrared
spectrum within the 1029.0–1033.4 cm−1 range and displayed the expected 1H and 13C-NMR signals,

Molecules 2020, 25, 3993
4 of 21
as well as the correct electrospray ionization (ESI) MS molecular ion peaks. Data are given in
1
the Materials and Methods section, and the H and 13C{1H} NMR spectra are collected in the
Supplementary Material.
2.2. Crystallographic Characterization of Sulfonated Salan Ligands 1–5 and Palladium (II) Complexes of PrHSS
(7) and BuHSS (8)
2.2.1. Sulfonated salan ligands 1–5
Although complexes of sulfonated salens and non-sulfonated salans have been used already as
homogeneous catalysts, the water-soluble Pd (II) complexes of sulfonated salans were first synthesized
and applied in our laboratory to catalyse C–C cross-coupling reactions in water. Ligands
obtained by an improved method consisting of sulfonation of the diamine precursors 21 25, and Pd (II)
complexes 10 were synthesized in reactions of the ligands with (NH4)2[PdCl4]. The compounds
1–5 were
–
6–
obtained in this work have not been characterized earlier by SC-XRD despite the considerable structural
differences that can be expected between the complexes depending on the nature and size of the
bridging unit of their sulfosalan ligand. For this reason, we undertook a structural study of the ligands
and complexes available in the form of crystals suitable for X-ray diffraction measurements. Luckily,
good quality crystals could be grown from water in the cases of 1 × 2H2O, PrHSS (
)-trans-CyHSS (5b), 5ca and 5cb. Unfortunately, we could not obtain crystals of dPhHSS (
water and this latter compound was crystallized from wet dimethylsulfoxide (DMSO). Na2[Pd(PrHSS)]
) and Na2[Pd(BuHSS)] ( ) were dissolved in 1M KOH solution layered by 2-propanol. All efforts to
2), BuHSS (
3),
(±
4) from
(7
8
grow crystals of 6, 9 and 10 remained so far unsuccessful.
Full details of the crystallographic results are outside the scope of this manuscript but are amply
described in the Supplementary Material. Nevertheless, a few basic findings are mentioned below.
Scarcely any similar compounds have been reported that could be compared to our new structures.
However, in such cases, a great degree of similarity is found. For example, the major difference
in the bond distances of 1 × 2H2O (Figure 1) and its already known solvomorph [44], 1 × DMSO,
is in the C8–C8(i) bond length (1.529(11) Å vs. 1.495 Å). The starting compound for the synthesis of
PrHSS (
various aromatic polycarboxylates [48] and SC-XRD studies revealed the protonation of the secondary
amine groups of PrHS, similar to the case of PrHSS ( ) (Figure 2). Comparison of the structure of
n-K4[µ8-BuHSS][µ2-H2O]4[H2O]6 published by us earlier [46] to the one of in this study (Figure 3),
2), i.e., N,N’-bis(2-hydroxybenzyl)-1,3-diaminopropane, PrHS, was previously crystallized with
2
3
shows, that the N1–C7–C1 angles are almost the same (114.28◦ and 114.4◦) in the two molecules,
and only the positions of the aromatic groups are different (Figure S15). Superposition of the structures
of the salan ligand, meso (RS,SR)-N,N’-bis(2-hydroxybenzyl)-1,2-diphenyl-1,2-diaminoethane [49] and
its sulfonated product, dPhHSS (4) (Figure 4) also shows high degree of similarity (Figure S20) and
proves that the starting salen underwent hydrogenation as well as sulfonation in the p-position relative
to the phenolic oxygen. The major difference between the structures of 5b (Figure 5) and its starting
material for synthesis, i.e., (
Perhaps the most important information is that, during the synthesis of cis-CyHSS
±
)-trans-CyS [50] is in the position of the aromatic rings (Figure S23).
2H2O (5ca
×
)
(Figure 5), the cis-conformation in the Schiff base formed in the reaction of salicylaldehyde and
cis-1,2-diaminocyclohexane is retained throughout hydrogenation and sulfonation. An interesting
observation is that, when a racemic mixture of cis-CyHSS and trans-CyHSS was subjected to
crystallization from water, the procedure yielded only crystals of cis-CyHSS (5cb) (Figure 5).
The cyclohexyl ring of the sulfonated product cis-CyHSS overlaps precisely with the cyclohexyl
ring in N,N’-di-5-nitrosalicylidene-(R,S)-l,2-cyclohexanediamine, published by Desiraju et al. [51
]
(see superposition of the molecules, Figure S27).

Molecules 2020, 25, 3993
5 of 21
Figure 2. Capped sticks representation of 2 × 5.5H2O. Lattice water molecules are omitted for clarity.
Figure 3. Capped sticks representation of 3. Symmetry code: (i) –x, 1–y, –z; Z’ = 0.5.
Figure 4. Capped sticks representation of 4 × H2O
×
DMSO. Solvents molecules are omitted for clarity.
Symmetry code: (i) 1–x, 1–y, 1–z.
Powder diffraction patterns of 1 × 2H2O and
3 were calculated from the cell parameters of the
crystals obtained from water and the ones measured experimentally on the powdery products yielded
by the synthesis; a good agreement was found with the experimentally determined diffractograms
(Figures S5 and S16). This shows that the direct products of syntheses and the crystals grown from
water have the same composition.
It is the general characteristics of the crystals of 1–5 that they contain various numbers of solvent
molecules, in most cases water. Due to the large number of water molecules and to the presence of
O- and N-atoms in the ligands, strong hydrogen bonds are formed within the lattices. In addition to
the hydrogen bonds, the crystal architecture is also stabilized by the π−π interactions between the
aromatic rings. Quantitative details are included in Tables S1–S7 and shown on the relevant crystal
packing diagrams of 1–5 in Supplementary Material.

Molecules 2020, 25, 3993
6 of 21
5b
5cb
5ca
Figure 5. Structures of (
× 6H2O (5cb; C2/c). Water molecules are omitted for clarity.
±
)-trans-CyHSS
×
7H2O (5b; P1), cis-CyHSS
×
2H2O (5ca; P21/c) and cis-CyHSS
2.2.2. Palladium (II) Complexes of PrHSS (7) and BuHSS (8)
Crystals of K2[Pd(PrHSS)] (70) K2[Pd(BuHSS)] (80) were obtained from solutions of Na2[Pd(PrHSS)]
) and Na2[Pd(BuHSS)] ( ) in 1M KOH solution layered by 2-propanol and were subjected to SC-XRD
(7
8
measurements at 5 ◦C. The packing diagrams of the two complexes reveal that the complexes are placed
within the lattice in layers and that the sulfosalan complexes are held together by inorganic polymer
chains (Figures S32–S35). In the case of both complexes, the 2D structures are shaped by the electrostatic
and van der Waals interactions between the K+ ions and the O-atoms of the sulfonate groups of the
ligand and water molecules, together with the hydrogen bonds within the lattice. Similar polymeric
chains were detected by us in crystals of the n-K4[µ8-BuHSS][µ2-H2O]4[H2O]6 sulfosalan [46] and in
the cases of Ni(II) and Cu(II) complexes of bis(salicylidene)-1,2-diaminocyclohexane, CyS [52].
Diffraction measurements were made on several crystals of both complexes at 150 K and at
room temperature. Since the crystals were twinned and the polymer chains were flexible, despite
all our efforts, all R values were higher than 10%, together with wR2-s > 25%. Due to these errors,
the bond lengths and angles determined for the complexes are not suitable for discussion. Nevertheless,
the SC-XRD measurements yielded clear atomic connectivities in both cases (Figure 6) and, together
with the spectroscopic data, prove the structures of the complexes. These are the first solid state
structures obtained for Pd (II)–sulfosalan complexes that, despite all uncertainties, show clearly the
steric differences imposed by C3 and C4 bridging alkyl chains in Pd (II)–sulfosalan complexes.

Molecules 2020, 25, 3993
7 of 21
Figure 6. Capped sticks views of K2[Pd(PrHSS)] (70). Symmetry code: (i) +x, 1/2–y, +z and
K2[Pd(BuHSS)] (80). Solvents and the flexible polymer chains linked together by K+ and water
molecules are omitted for clarity.
2.3. Catalytic Properties of the Pd(II)–Sulfosalan Complexes in Suzuki–Miyaura Cross-Coupling Reactions
Earlier, we have established that some of the Pd (II)-sulfonated salan complexes were active
catalysts for the Suzuki–Miyaura cross-coupling reactions in aqueous media. The reactions could
be performed under aerobic conditions, and the catalysts showed outstanding stability in aqueous
solutions. One of the aims of the present study was the comparison of catalytic properties of
Pd (II)-sulfonated salan complexes with various linker groups, L, in the Suzuki–Miyaura cross-coupling
and the exploration of the usefulness of the best catalysts for the reactions of a wide range of
substrates under various conditions. For this purpose, in addition to the already known sulfosalans,
we synthesized new ligands of such types starting with cis- and trans-isomers of 1,2-cyclohexanediamine
and developed synthetic procedures for 7 and 9, too.
For the comparison of the Pd (II)–sulfosalan catalysts 6–10, the Suzuki–Miyaura cross-coupling
of iodobenzene and phenylboronic acid were chosen as a standard reaction (Figure 7). With all
catalysts, fast and clean reactions were observed. The reaction mixtures retained their original yellow
colour throughout the reaction, and no metal precipitation was detected. Conversions (calculated for
iodobenzene) were established by gas chromatography after extraction of the reaction mixtures with
CHCl3. The results are shown Figure 8.
Cat.: 6 - 10
B(OH)2
I
Cs2CO3, H2O
80 °C,
Figure 7. Suzuki–Miyaura cross-coupling of iodobenzene and phenylboronic acid catalysed by Pd
(II)–sulfosalan complexes in water.

Molecules 2020, 25, 3993
8 of 21
100
80
60
40
20
0
6
7
10a
10b
10c
8
9
Figure 8. Comparison of the catalytic activity of Pd (II)–sulfosalan complexes
Suzuki–Miyaura cross-coupling reaction of iodobenzene and phenylboronic acid: Conversions are
calculated for iodobenzene. Catalysts: Na2[Pd(HSS)] ( ), Na2[Pd(PrHSS)] ( ), Na2[Pd(BuHSS)] ( ),
Na2[Pd(dPhHSS)] ( ), rac-Na2[Pd(CyHSS)] (10a), Na2[Pd(trans-CyHSS)] (10b) and Na2[Pd(cis-CyHSS)]
10c). Conditions: 2.0
6–10 in the
6
7
8
9
(
×
10−8 mol catalyst, 5.0
×
10−4 mol iodobenzene, 7.5
×
10−4 mol phenylboronic
acid, 5 × 10−4 mol Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 30 min.
Figure 8 shows that there are substantial differences in the catalytic activities of the various
Pd (II)–sulfosalan complexes, with Na2[Pd(HSS)] (
Na2[Pd(dPhHSS)] ( ) being the most active (93% conversion) catalyst. The exact reaction mechanism
of the Suzuki–Miyaura cross-couplings catalysed by Pd (II)–sulfosalan complexes in aqueous media
is presently unknown. For the reaction of Na2[Pd(HSS)] ( ) and Na2[Pd(BuHSS)] ( ) with H2,
we obtained evidence of the need for a vacant coordination site for the oxidative addition of H2 [43 44].
6) being the least effective (14% conversion) and
9
6
8
,
In the present case, the catalytic activity increased with increasing length of the linker chain in the
order 6 (14%) < 7 (35%) < 8 (72%). This is also the order of increasing flexibility of the coordination
sphere around the Pd (II) central ion as can be judged also from the solid state structures of
(Figure 7). The Pd (II) complexes with sulfosalan ligands derived from 1,2-diaminocyclohexanes
10a 10c) catalysed the Suzuki–Miyaura cross-coupling of iodobenzene and phenylboronic acid with
equal activities (58%, 60% and 60%, respectively) which is significantly higher than that of Na2[Pd(HSS)]
), having also a two-carbon linker group between the N-atoms of the ligand. The conversion data
also show that the catalytic performance is insensitive to the stereochemistry of the ligands in 10b and
10c. Finally, the outstandingly high catalytic activity of Na2[Pd(dPhHSS)] ( ) (which also contains
7 and
8
(
–
(6
9
a two-carbon linker group in its ligand) may stem from the space requirement of the two phenyl
substituents. All these observations are in agreement with the assumption that longer and more
substituted linker groups in the sulfosalan ligands may facilitate de-coordination of one of the phenolate
oxygens and, in such a way, may lead to creation of a vacant coordination site on Pd (II) which is
manifested in higher catalytic activities.
The catalytic properties of the two most active catalysts for the Suzuki–Miyaura cross-coupling
reactions, Na2[Pd(dPhHSS)] (
synthetic viewpoint.
9) and Na2[Pd(BuHSS)] (8), were studied in some detail, mostly from a
Table 1 shows conversion of reactions between a variety of aryl halides and arylboronic acids
(two heteroarylboronic acids were also included). The data show that is able to catalyse the reaction
with very high activity, with turnover frequencies (TOF) up to 40,000 h−1 (TOF = (mol reacted substrate)
(mol catalyst
time)−1). As generally observed, aryl iodides reacted faster than aryl bromides (entries
9
×
1/14, 6/11 and 12/13); however, with extended reaction times, medium to high conversions could be
achieved with aryl bromides, too (entries 8, 9, 11 and 16). The catalyst tolerates several common
functional groups; however, aryl or hetaryl halides containing good donor atoms for Pd (II) reacted
slower (entries 6, 11, 17 and 20).

Molecules 2020, 25, 3993
9 of 21
Table 1. Suzuki–Miyaura cross-coupling reactions of various boronic acids with different aryl halides
catalysed by Na2[Pd(dPhHSS)].
Na2[Pd(dPhHSS)]
R
B(OH)2
X
R
Cs2CO3, H2O
80 °C,
R'
R'
X = I, Br
TOF (h−1
)
Product
(ArX)/(Catalyst) Ratio
Reaction Time (min)
Conversion (%)
1 a
2 a
25,000
30
80
40,000
25,000
25,000
30
30
58
13
29,000
6500
3 a
4 a
5 a
6 a
25,000
25,000
5000
30
34
35
86
17,000
17,500
2150
30
120
7 a
3000
60
38
1140
8 b
9 b
3000
3000
120
120
70
62
1050
930
10 a
11 b
12 a
13 b
14 b
3000
1000
1000
1000
1000
60
60
30
30
60
27
77
810
770
100
82
2000
1640
500
71
15 b
16 b
17 b
1000
1000
1000
15
60
60
100
95
4000
950
50
500

Molecules 2020, 25, 3993
10 of 21
Table 1. Cont.
Na2[Pd(dPhHSS)]
R
B(OH)2
X
R
Cs2CO3, H2O
80 °C,
R'
R'
X = I, Br
TOF (h−1
)
Product
(ArX)/(Catalyst) Ratio
Reaction Time (min)
Conversion (%)
100 c
18 b
1000
15
19 b
20 a
500
500
60
60
10
9
50
45
Conditions: 1.0
×
10−6–2.0
×
×
10−8 mol Na2[Pd(dPhHSS)] catalyst, 5.0
×
10−4 mol aryl halide, 7.5
×
10−4 mol boronic
b
acid derivative, 5.0
10−4 mol Cs2CO3, solvent: H2O (V = 3 mL) and T = 80 ◦C. a Aryl iodide. Aryl bromide.
c
Conversion determined by 1H-NMR.
Since aryl halides have limited solubility in water, in fact, these reactions take place
in aqueous-organic biphasic systems and the actual concentration of the substrates in the
catalyst-containing aqueous phase may be very low—this can also lead to low conversions and
TOF-s and may mask the chemical differences in reactivity.
Under otherwise identical conditions, the reaction rate depends on the arylboronic acid to aryl
halide molar ratio. This is exemplified in Table 2. In view of the data in the table, in most of our
experiments, a 50 mol % excess of a boron derivative over the aromatic halide was used.
Table 2. Effect of the (phenylboronic acid)/(iodobenzene) ratio on the reaction rate of their
Suzuki–Miyaura cross-coupling catalysed by Na2[Pd(dPhHSS)].
TOF (h−1
)
(Phenylboronic acid)/(Iodobenzene) Ratio Conversion (%)
1.5/1
1.25/1
1/1
80
65
51
40000
32500
25500
Conditions: 2.0
×
10−8 mol Na2[Pd(dPhHSS)], 5.0
×
10−4 mol iodobenzene, 5.0
×
10−4 mol Cs2CO3, solvent: H2O (V
= 3 mL), T = 80 ◦C and t = 30 min.
The catalytic performance and substrate scope of Na2[Pd(dPhHSS)] (9) and Na2[Pd(BuHSS)] (8)
are further demonstrated by the data in Tables 3 and 4, respectively. It seems that the chemical nature
of the substituents in the boronic acid derivative or in the aryl halide has only a limited influence on
the rate of formation of the appropriate biphenyls.

Molecules 2020, 25, 3993
11 of 21
Table 3. Suzuki–Miyaura cross-coupling reactions of boronic acid derivatives with bromobenzene
and 4-bromoacetophenone.
Boronic Acid
Conversion (%) R’ = H
Conversion (%) R’ = COCH3
1
2
3
4
68
66
86
70
73
71
100
100
5
20
27
6
7
43
92
63
81
8
9
74
78
56
96
42
62
10
Conditions: 1.7
×
10−7 mol Na2[Pd(dPhHSS)], 5.0
×
10−4 mol aryl halide, 1.5
×
10−3 mol boronic acid, 5.0
×
10−4 mol
Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 1 h.

Molecules 2020, 25, 3993
12 of 21
Table 4. Suzuki–Miyaura cross-coupling reactions of 4-tolylboronic and 4-methoxyphenylboronic acids
with various aryl halides.
Aryl Halide
Conversion (%) R = CH3
Conversion (%) R = OCH3
1
2
100
100
100
81
65
41
3
4
5
6
94
82
89
78
72
100
7
100
100
Conditions: 5.0
×
10−7 mol Na2[Pd(BuHSS)], 5.0
×
10−4 mol aryl halide, 7.5
×
10−4 mol 4-tolylboronic acid or
4-methoxyphenylboronic acid, 5.0 × 10−4 mol Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 1 h.
Na2[Pd(dPhHSS)] catalysed also the Suzuki–Miyaura cross-coupling of phenylboronic acid with
various aryl dihalides; the results are shown in Table 5. It is interesting to see that, with this catalyst,
the major (in most cases exclusive) products were the corresponding terphenyl derivatives (entries
2–4). Only in the case of an aryl dihalide with two different halide substituents was a small conversion
to the corresponding halogenated biphenyl detected. Such a high selectivity is not generally observed;
see the results with the Na2[Pd(BuHSS)] catalyst below.
Table 5. Suzuki–Miyaura cross-coupling of phenylboronic acid and aryl dihalides catalysed by
Na2[Pd(dPhHSS)].
X
Na2[Pd(dPhHSS)]
2
X
B(OH)2
Cs2CO3, H2O
80 °C,
X
X= I, Br
A
B
Yield (%)
Aryl Dihalide
(Substrate)/(Catalyst)
A
B
1
2
3
4
4-Bromo-1-iodobenzene
1,2-Dibromobenzene
1,3-Dibromobenzene
1,4-Dibromobenzene
3000/1
3000/1
3000/1
3000/1
5
0
0
0
54
12
53
18
Conditions: 1.7
×
10−7 mol [Pd(dPhHSS)], 5.0
×
10−4 mol aryl dihalide, 1.5
×
10−3 mol phenylboronic acid,
5.0 × 10−4 mol Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 1 h.
It is shown by the data in Table 3 (entries 5 and 10) that both NaBPh4 and KBF3Ph can be
used as phenyl group donors in the Suzuki–Miyaura reaction with Na2[Pd(dPhHSS)] as the catalyst.

Molecules 2020, 25, 3993
13 of 21
Although both salts are water-soluble, their use results in modest or medium high conversions.
Na-tetraphenylborate was used in Suzuki–Miyaura cross-coupling with aryl dihalides catalysed
by Na2[Pd(dPhHSS)]; however, the reactions proceeded with low yields (in 1 h reaction time) and
incomplete selectivity (Table 6).
Table 6. Suzuki–Miyaura cross-coupling reactions of Na-tetraphenylborate with aryl dihalides catalysed
by Na2[Pd(dPhHSS)].
Yield (%)
Aryl Dihalide
(Substrate)/(Catalyst)
A
B
1
2
3
4
4-Bromo-1-iodobenzene
1,2-Dibromobenzene
1,3-Dibromobenzene
1,4-Dibromobenzene
3000/1
3000/1
3000/1
3000/1
3
0
0
4
11
16
4
4
Conditions: 1.7
×
10−7 mol Na2[Pd(dPhHSS)], 5.0
×
10−4 mol aryl dihalide, 1.5
×
10−3 mol NaBPh4, 5.0
×
10−4 mol
Cs2CO3, solvent: H2O (V = 3 mL), T = 80 ◦C and t = 1 h.
The catalytic features of Na2[Pd(dPhHSS)] in the Suzuki–Miyaura cross-coupling of aromatic
dihalides were compared to those of Na2[Pd(BuHSS)]; the latter showed the second highest activity
(Figure 8) in cross-coupling of phenylboronic acid and iodobenzene. According to the data in Table 7,
Na2[Pd(BuHSS)] is also a very active catalyst for this reaction, since in the cases of phenylboronic
and 4-tolylboronic acids, uniformly high (close or above 90%) total conversions of the dihalides were
achieved (4-methoxyphenylboronic acid reacted less readily). However, although the yield of biphenyls
was generally lower than those of the terphenyls, the reactions were far from selective even with
aromatic halides containing two identical halogens. The highest biphenyl–terphenyl selectivity was
17:74, obtained in the reaction of 4-tolylboronic acid and 4-bromo-1-iodobenzene.
Table 7.
Suzuki–Miyaura cross-coupling reactions of phenylboronic, 4-tolylboronic and
4-methoxyphenylboronic acids with aryl dihalides catalysed by Na2[Pd(BuHSS)].
Yield (%) R = H
Yield (%) R = CH3
Yield (%) R = CH3O
Aryl Halide
A
B
A
B
A
B
1
2
3
4
4-Bromo-1-iodobenzene
1,2-Dibromobenzene
1,3-Dibromobenzene
1,4-Dibromobenzene
42
17
24
15
53
34
68
50
17
30
27
15
74
64
68
70
14
25
20
30
64
27
37
22
Conditions: 5.0
4-tolylboronic acid or 4-methoxyphenylboronic acid; 5.0
and t = 1 h.
×
10−7 mol Na2[Pd(BuHSS)]; 5.0
×
10−4 mol aryl dihalide; 1.5
×
10−3 mol phenylboronic acid,
×
10−4 mol Cs2CO3; solvent: H2O (V = 3 mL); T = 80 ◦C;
3. Materials and Methods
With the exception of the salan ligands and their Pd complexes, all chemicals and solvents were
high-quality commercial products purchased from Sigma-Aldrich/Merck, St. Louis, Missouri, USA;
VVR International, West Chester, Pennsylvania, USA; and Molar Chemicals Kft., Halásztelek, Hungary
and were used without further purification. Good quality ion-exchanged water was used throughout
(S ≤ 2 µS). Gases (Ar and N2) were supplied by Linde Gáz Magyarország Zrt., Répcelak, Hungary.

Molecules 2020, 25, 3993
14 of 21
3.1. Synthesis of the Sulfosalan Ligands
HSS [44], PrHSS [45], BuHSS [46] and rac-CyHSS [46] were synthesized according to published
methods. Synthetic procedures for dPhHSS as well as for cis- and trans-CyHSS are described below.
3.1.1. 1,2-Diphenyl-N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,2-diaminoethane-dPhHSS
This was prepared from the appropriate salen derivative (dPhS) by hydrogenation to afford the
benzylamino intermediate (dPhHS) followed by sulfonation to yield dPhHSS.
Synthesis of dPhS:
meso-1,2-Diphenyl-ethylenediamine (4.0 g, 18.80 mol) was added into a round-bottom flask
containing 50 mL ethanol. To this solution, salicylaldehyde (3.70 mL, 37.60 mmol) was added and
the mixture was stirred at 25 ◦C for 1 h, resulting in formation of a yellow precipitate. The reaction
mixture was filtered, and the product was washed with ethanol to obtain dPhS as a yellow crystalline
solid. Yield was 7.58 g (17.93 mmol), 95%, yellow crystalline solid.
1H-NMR (d6-DMSO, 360 MHz,
δ): 5.06 (s, 2H, –CH–CH–), 6.85 (d, J = 8.0 Hz, 4H, CHarom),
7.20–7.32 (m, 12H, CHarom), 8.43 (s, 2H, CH=N–), 13.17 (s, 2H, –OH).
13C{1H} NMR (d6-DMSO, 90 MHz,
118.69, 118.50, 116.34, 77.70.
Synthesis of dPhHS
δ): 166.17, 160.11, 139.93, 132.53, 131.75, 128.23, 127.86, 127.44,
dPhS (4.00 g, 6.87 mmol) was dissolved in methanol (300 mL) followed by the addition of 4
equivalents (1.04 g, 27.48 mmol) of sodium borohydride in 100 mL of methanol under constant stirring
at room temperature. The mixture was then stirred at reflux for 30 min. The hot reaction mixture was
added dropwise into 600 mL of water with continuous stirring. The white precipitate was filtered,
washed with water and dried under vacuum. Yield was 3.90 g (6.67 mmol), 97%, white solid.
1H-NMR (d6-DMSO, 360 MHz,
δ): 3.00 (d, 14.0 Hz, 2H, CH2–NH) and 3.11 (d, 14.0 Hz, CH2–NH),
3.49 (s, 2H, –CH–CH–), 6.28–6.32 (m, 4H, CHarom), 6.46 (d, J = 7.2 Hz, 2H, CHarom), 6.68 (t, J = 7.3 Hz,
2H, CHarom), 6.94–7.04 (m, 10H, CHarom).
13C{1H} NMR (d6-DMSO, 90 MHz, δ: 156.51, 140.81, 128.41, 128.04, 127.98, 127.65, 127.13, 124.60,
118.32, 115.07, 66.82, 47.75.
Synthesis of dPhHSS
In a round-bottom flask, dPhHS (1.00 g, 2.34 mmol) was added in small portions to a mixture
of 4 mL of 20% fuming sulfuric acid (oleum) and 1 mL of concentrated sulfuric acid. The flask was
cooled in ice water, and the mixture was stirred for 60 min. Then, the content of the flask was carefully
added to 25 mL of cold water. The pH of the reaction mixture was set to 4 with a concentrated NaOH
solution. Then, the mixture was cooled for 24 h, during which a white precipitate formed. The solid
was collected by filtration, washed with cold water and dried under vacuum. The compound thus
obtained is the zwitterionic free acid form of the ligand, which is slightly soluble in water.
Yield was 825.05 mg (1.41 mmol), 60%, white solid.
1H-NMR (D2O, 360 MHz,
3.89 (s, 2H, –CH–CH–), 6.43 (d, J = 8.4 Hz, 2H, CHarom), 7.05 (s, 2H, CHarom), 7.36–7.54 (m, 12H, CHarom).
13C{1H} NMR (D2O, 90 MHz,
): 169.22, 139.50, 129.10, 128.28, 127.26, 126.64, 126.29, 125.56,
118.33, 66.02, 46.27.
δ): 3.14 (d, J = 14.0 Hz, 2H, CH2–NH), 3.27 (d, J = 14.0 Hz, 2H, CH2–NH),
δ
IR (ATR), ν/cm−1: 594.7, 697.8, 759.0, 1033.6, 1101.7, 1181.0, 1285.9, 1590.8.
ESI-MS for C28H28N2O8S2 (m/z): calcd for [M − H]− 583.121, found 583.121.
3.1.2. N,N’-bis(2-Hydroxy-5-sulfonatobenzyl)-cis-1,2-diaminocyclohexane-cis-CyHSS
This was prepared from the appropriate salen derivative (cis-CyS) by hydrogenation to afford the
benzylamino intermediate (cis-CyHS) followed by sulfonation to yield cis-CyHSS.
Synthesis of cis-CyS

Molecules 2020, 25, 3993
15 of 21
According to Section 3.1.1, 1.05 mL (8.76 mmol) of cis-1,2-diaminocyclohexane and 1.83 mL
(17.51 mmol) of salicylaldehyde yielded 2.50 g (7.71 mmol), 88%, yellow crystalline solid.
1H-NMR (d6-DMSO, 360 MHz,
δ): 1.54–1.87 (m, 8H, –CH2–CH2–), 3.67 (s, 2H, CH–CH), 6.82–6.9
(m, 4H, CHarom), 7.31 (t, J = 7.4 Hz, 2H, CHarom), 7.41 (d, J = 7.3, 2H, CHarom), 8.56 (s, 2H, –CH=N–),
13.66 (s, 2H, –OH).
13C{1H} NMR (d6-DMSO, 90 MHz,
δ): 165.05, 160.76, 132.25, 131.72, 118.66, 118.42, 116.45, 68.12,
30.42, 21.95.
Synthesis of cis-CyHS
According to Section 3.1.1, 2.50 g (7.71 mmol) of cis-CyS and 1.17 g (30.84 mmol) of sodium
borohydride yielded 2.23 g (6.79 mmol), 88%, white crystalline solid.
1H-NMR (d6-DMSO, 360 MHz,
δ): 1.25–1.36 (m, 4H, –CH2–CH2–), 1.54–1.65 (m, 4H, –CH2–CH2–),
2.72 (s, 2H, –CH–CH–), 3.69 (d, J = 13.9 Hz, CH2–NH), 3.78 (d, J = 13.9 Hz, CH2–NH), 6.72 (s, 2H, CHarom),
7.07 (d, J = 7. 6 Hz, 2H, CHarom).
13C{1H} NMR (d6-DMSO, 90 MHz,
27.11, 21.97.
Synthesis of cis-CyHSS
δ): 157.02, 128.74, 127.79, 125.07, 118.50, 115.30, 55.32, 47.58,
According to Section 3.1.1, 1 g (3.06 mmol) CyHS, 4 mL of 20% fuming sulfuric acid (oleum) and
1 mL of concentrated sulfuric acid yielded 821 mg (1.68 mmol), 55%, white crystalline solid.
1H-NMR (D2O, 360 MHz,
δ): 1.33–1.69 (m, 8H, –CH2–CH2–), 2.83 (s, 2H, –CH–CH–),
3.59 (d, J = 13 Hz, CH2–NH), 3.69 (d, J = 13 Hz, CH2–NH), 6.60 (d, J = 8.7 Hz, 2H, CHarom), 7.43–7.47
(m, 4H, CHarom).
13C{1H} NMR (D2O, 90 MHz,
δ): 169.31, 127.79, 127.39, 126.46, 126.18, 118.57, 55.69, 46.69,
26.81, 21.81.
IR (ATR), ν/cm−1: 588.8, 6923.0, 846.2, 1039.3, 1101.6, 1138,2, 1435.8, 1604.7.
ESI-MS for C20H26N2O8S2 (m/z): calcd for [M + H]+ 487.120, found 487.122 and [M + Na+]+
509.102, found 509.104.
3.1.3. N,N’-bis(2-Hydroxy-5-sulfonatobenzyl)-trans-1,2-diaminocyclohexane - trans-CyHSS
This was prepared from the appropriate salen derivative (trans-CyS) by hydrogenation to afford
the benzylamino intermediate (trans-CyHS) followed by sulfonation to yield trans-CyHSS.
Synthesis of trans-CyS
According to Section 3.1.1, 3.06 mL (25.50 mmol) of trans-1,2-diaminocyclohexane and 5.0 mL
(51.00 mmol) of salicylaldehyde yielded 7.89 g (24.32 mmol), 95%, yellow crystalline solid.
1H-NMR (d6-DMSO, 360 MHz,
δ): 1.39–1.45 (m, 2H, –CH2–CH2–), 1.59–1.62 (m, 2H, –CH2–CH2–),
1.76–1.88 (m, 4H, –CH2–CH2–), 3.36 (s, 2H, CH–CH), 6.81 (d, J = 8.0 Hz, 4H, CHarom), 7.24–7.29
(t, J = 8.1 Hz, 2H, CHarom), 7.32–7.35 (d, J = 7.3, 2H, CHarom), 8.47 (s, 2H, –CH=N–), 13.32 (s, 2H, –OH).
13C{1H} NMR (d6-DMSO, 90 MHz,
32.48, 23.67.
Synthesis of trans-CyHS
δ): 165.00, 160.33, 132.16, 131.54, 118.48, 116.29, 71.29,
According to Section 3.1.1, 7.90 g (24.04 mmol) of trans-CyS and 3.64 g (61.65 mmol) of sodium
borohydride yielded 7.11 g (21.65 mmol), 90%, white crystalline solid.
1H-NMR (d6-DMSO, 360 MHz,
δ): 1.08–1.23 (m, 4H, –CH2–CH2–), 1.67 (s, 2H, –CH2–), 2.07–2.10
(m, 2H, –CH2–), 2.51 (s, 2H, –CH–CH–), 3.79 (d, J = 13.7 Hz, 2H, CH2–NH), 3.92 (d, J = 13.7 Hz, 2H,
CH2–NH), 6.74–6.78 (t, J = 7.2 Hz, 2H, CHarom), 6.86 (d, J = 7.9 Hz, 2H, CHarom), 7.08–7.12 (t, J = 7.7 Hz,
2H, CHarom), 7.24 (d, J = 7.2 Hz, 2H, CHarom).
13C{1H} NMR (d6-DMSO, 90 MHz,
28.73, 24.01.
Synthesis of trans-CyHSS
δ): 156.04, 129.63, 128.53, 123.28, 118.80, 115.15, 58.91, 44.95,
According to Section 3.1.1, 1 g (3.06 mmol) trans-CyHS, 4 mL of 20% fuming sulfuric acid (oleum)
and 1 mL of concentrated sulfuric acid yielded 868 mg (1.78 mmol), 58%, white crystalline solid.

Molecules 2020, 25, 3993
16 of 21
1H-NMR (D2O, 360 MHz,
δ): 1.05–1.17 (m, 4H, –CH2–CH2–), 1.57–1.60 (m, 2H, –CH2–), 1.89–1.92
(m, 2H, –CH2–), 2.34–2.37 (m, 2H, –CH2–NH–), 3.59–3.67 (m, 4H, CH2–NH), 6.55 (d, J = 8.1 Hz, 2H,
CHarom), 7.38–7.45 (m, 4H, CHarom).
13C{1H} NMR (D2O, 90 MHz),
δ: 169.13, 128.13, 127.18, 126.34, 126.10, 118.51, 59.47, 46.48,
29.68, 24.06.
IR (ATR), ν/cm−1: 587.5, 694.4, 840.3, 1033.3, 1165.4, 1207.3, 1281.3, 1598.1
ESI-MS for C20H26N2O8S2 (m/z): calcd for [M + H]+ 487.119, found 487.121 and [M + Na+]+
509.102, found 509.104.
3.2. Synthesis of the Pd–Sulfosalan Complexes
3.2.1. Synthesis of Na2[Pd(PrHSS)]
In water (4 mL), 106.75 mg (0.24 mmol) of PrHSS and 73.9 mg (0.26 mmol) of (NH4)2[PdCl4] were
dissolved. The pH was set to 7.5 with concentrated NaOH, and the reaction mixture was stirred at 60 ◦C
for 10 h. Then, the solution was cooled to room temperature, and Na2[Pd(PrHSS)] was precipitated by
addition of 25 mL ice-cold ethanol. The solid was filtered, washed with absolute ethanol and dried
under vacuum.
Yield: 129 mg (0.22 mmol), 92%, yellow solid.
1H-NMR (D2O, 273 K, 360 MHz,
δ
): 1.37–1.49 (m, 1H,
CH2CH2 ), 2.73 (t, J = 12.4 Hz, 2H, CH2CH2), 3.23 (d, J = 12.5 Hz,
NH), 3.29 (d, J = 12.5 Hz, 2H, CH2 NH), 6.84 (d, J = 9.0 Hz, 2H, CHarom), 7.36 (s, 2H, CHarom),
−
CH2CH2 ), 1.89 (d, J = 15.9 Hz, 1H,
−
−
CH2CH2
−
), 2.48 (d, J = 12.7 Hz, 2H,
−
−
2H, CH2
−
−
7.44–7.47 (m, 2H, CHarom).
13C{1H} NMR (D2O, 90 MHz,
δ
/ppm): 167.27, 130.40, 128,17, 127.69, 126.47, 118.43, 52.47, 51.98, 26.67.
IR (ATR), ν/cm−1: 602.5, 707.8, 823.7, 1038.48, 1103.5, 1198.2, 1290.5, 1477.9
ESI-MS C17H18N2O8S2PdNa2 (m/z): calcd for [M − Na+]− 570.945, found 570.945.
3.2.2. Synthesis of Na2[Pd(dPhHSS)]
According to Section 3.2.1, 140.32 mg (0.24 mmol) of dPhHSS and 73.9 mg (0.26 mmol) of
(NH4)2[PdCl4] yielded 149 mg (0.20 mmol), 84%, yellow solid.
1H-NMR (D2O, 298K, 360 MHz,
δ): 2.95 (d, J = 13.0 Hz, 1H, CH2–NH), 3.22 (d, J = 13.0 Hz, 1H,
CH2–NH), 3.80 (d, J = 13.0, 1H, CH2–NH), 4.25 (d, J = 13.0, 1H, CH2–NH), 4.29 (d, J = 4.0 Hz, 1H,
CH–CH), 4.61 (d, J = 4.0 Hz 1H, CH–CH), 6.88–7.55 (m, 16H, CHarom).
13C{1H} NMR (D2O, 90 MHz,
δ): 164.47, 163.66, 130.46, 128.86, 128.68, 128.01, 127.58, 126.89,
126.67, 126.55, 123.15, 121.46, 117.98, 117.69, 72.85, 70.36, 51.39, 48.12.
IR (ATR), ν/cm−1: 605.8, 708.8, 1028.7, 1106.1, 1175.4, 1300.8, 1473.1, 1592.7
ESI-MS for C28H24Na2N2O8S2Pd (m/z): calcd for [M − 2Na]2− 343.001; found 342.992.
3.2.3. Synthesis of Na2[Pd(cis-CyHSS)]
According to Section 3.2.1, 116.77 mg (0.24 mmol) of cis-CyHSS and 73.9 mg (0.26 mmol) of
(NH4)2[PdCl4] yielded 121 mg (0.19 mmol), 79%, yellow solid.
1H-NMR (D2O, 298 K, 360 MHz,
δ
): 1.39–2.21 (m, 8H, CH2–CH2), 3.59–3.69 (m, 4H, CH2–NH),
4.44–4.47 (m, 2H CH–CH), 6.89–6.91 (m, 2H, CHarom), 7.53–7.57 (m, 4H, CHarom).
1H-NMR (D2O, 268 K, 360 MHz,
): 1.19–2.01 (m, 8H, CH2–CH2), 3.14 (d, J = 13.4, 1H, CH2–N),
δ
3.41 (d, J2 = 12.9 Hz, 2H, CH–CH), 3.47 (d, J = 13.4, 1H, CH2–N), 3.89 (d, J = 13.4, 1H, CH2–N),
4.24 (d, J = 13.4, 1H, CH2–N), 6.70 (d, J = 8.4 Hz, 2H, CHarom), 7.32–7.38 (m, 4H, CHarom).
13C{1H} NMR (D2O, 90 MHz), δ: 165.52, 129.41, 127.70, 123.60, 118.70, 65.11, 51.49, 24.26, 20.61.
IR (ATR), ν/cm−1: 596.1, 634.3, 707.9, 1028.4, 1107.2, 1170.8, 1301.2, 1475.2, 1592.5
ESI-MS for C20H22Na2N2O8S2Pd (m/z): calcd for [M + Na]+ 656.954; found 656.956.

Molecules 2020, 25, 3993
17 of 21
3.2.4. Synthesis of [Pd(trans-CyHSS)]
According to Section 3.2.1, 116.77 mg (0.24 mmol) of trans-CyHSS and 73.9 mg (0.26 mmol) of
(NH4)2[PdCl4] yielded 132 mg (0.21 mmol), 88%, yellow solid.
1H-NMR (D2O, 298 K, 360 MHz,
δ): 1.25 (s, 4H, CH2–CH2), 1.80 (s, 2H, CH2–CH2), 2.51 (s, 2H
CH2–CH2), 2.79 (s, 2H, CH2–CH2), 3.74 (d, J = 13.3 Hz, 2H, CH2–NH), 4.17 (d, J = 13.3 Hz, 2H, CH–NH),
6.87–6.90 (m, 2H, CHarom), 7.52–7.55 (m, 4H, CHarom).
1H-NMR (D2O, 268 K, 360 MHz,
δ): 0.75 (s, 4H, CH2–CH2), 1.30 (s, 2H, CH2–CH2), 2.04 (s, 2H
CH2–CH2), 2.30 (s, 2H, CH–CH), 3.28 (d, J = 13.3 Hz, 2H, CH2–NH), 3.68 (d, J = 13.3 Hz, 2H, CH–NH),
6.38 (d, J = 8.3 Hz, 2H, CHarom), 7.01–7.04 (m, 4H, CHarom).
13C{1H} NMR (D2O, 90 MHz,
δ): 16.54, 129.40, 128.29, 127.72, 123.53, 118.74, 67.34, 50.29, 29.44, 24.14.
IR (ATR), ν/cm−1: 606.7, 708.8, 1033.3, 1105.3, 1165.3, 1298.4, 1473.3, 1590.4
ESI-MS for C20H22Na2N2O8S2Pd (m/z): calcd for [M + Na]+ 656.954; found 656.956.
3.2.5. Preparation of Pd–Salan Stock Solutions
In water (10 mL), 0.1 mmol of the appropriate salan and 28.4 mg (0.1 mmol) of (NH4)2[PdCl4]
◦
were dissolved. The pH was set to 7.5 with 5 M NaOH, and the solution was stirred at 60 C for
10 h. With time, the light brown solution turned bright yellow. Aliquots of such stock solutions of the
1
catalysts were added to the C–C cross-coupling reaction mixtures. H-NMR spectra of these stock
solutions are identical to those prepared by dissolution of isolated complexes (Figures S110 and S111).
3.3. General Procedure
1H and 13C{1H} NMR spectra were recorded on a Bruker Avance 360 MHz spectrometer
(Bruker, Billerica, MA, USA) and were referenced to residual solvent peaks. Single crystal X-ray
diffraction (SC-XRD) measurements were performed using a Bruker D8 Venture diffractometer,
SuperNova X-ray diffractometer system, and the methods and software described in [53–60].
The crystallographic data for all compounds were deposited in the Cambridge Crystallographic
Data Centre (CCDC) with the No. CCDC 2020275–2020282 and 2020437. Details of the structure
determinations are found in the Supplementary Material.
Infrared spectra were recorded on a Perkin Elmer Spectrum Two FT-IR Spectrometer in attenuated
total reflectance (ATR) mode.
Gas chromatographic measurements were done with the use of an Agilent Technologies
7890A instrument (Agilent Technologies, Santa Clara, CA, USA) equipped with a HP-5,
0.25 µm × 30 m × 0.32 mm or an OPTIMA (30 m
×
0.32 mm
×
1.25 µm) column, and a flame ionization
detector 300 ◦C; the carrier gas was nitrogen 1.9 mL/min.
ESI-TOF-MS measurements were carried out on a BRUKER BioTOF II ESI-TOF spectrometer in
positive ion mode or on a Bruker maXis II MicroTOF-Q type Qq-TOF-MS instrument (Bruker Daltonik,
Bremen, Germany) both in positive and negative ion modes. The mass spectra were calibrated internally
using the exact masses of sodium formate clusters. The spectra were evaluated using Compass Data
Analysis 4.4 software from Bruker.
All catalytic Suzuki–Miyaura cross-coupling reactions were carried out under air. The reaction
temperatures were kept constant by using a thermostated circulator (set to 80.0
were identified by comparison of their retention time with those of known standard compounds.
±
0.1 ◦C). The products
4. Conclusions
All investigated Pd (II)–sulfosalan complexes 6–10 showed high catalytic activities in the
Suzuki–Miyaura reactions of aryl halides and phenylboronic acid derivatives in water and air
at 80 ◦C. The catalytic activity of a particular complex depended on the length of the linker group
between the secondary N-atoms of the sulfosalan ligand and/or on the steric congestion around these

Molecules 2020, 25, 3993
18 of 21
donor atoms. With the most active catalyst, Na2[Pd(dPhHSS)] (9), a TOF = 40,000 h−1 was achieved in
the reaction of iodobenzene and phenylboronic acid.
Supplementary Materials: The following are available online, ORTEP views of ligands and Pd complexes (9),
crystal lattice packing views with indication of π–π interactions and H-bond networks (17), tables of hydrogen
bonds in ligands and complexes (7), calculated and experimental powder diffraction patterns for the crystals
of 1 × 2 H2O and
3, comparison (superposition) of known and newly determined structures of the ligands (7),
table of crystal data and diffraction measurements, 1H and 13C NMR spectra (Figures S37–S111) of ligands
Pd(II)-complexes 6–10, starting materials (salens 11–15) and synthetic intermediates (salans 21–25).
1–5,
Author Contributions: Conceptualization, all authors (S.B., K.V.,
Á.K., A.U., F.J.); methodology, S.B and A.U.;
investigation, S.B. and A.U.; discussion of experimental results, all authors; writing—original draft preparation,
S.B., A.U. and F.J.; writing—review and editing, all authors; visualization, S.B. and A.U.; supervision, F.J. All authors
have read and agreed to the published version of the manuscript.
Funding: The research was supported by the EU and cofinanced by the European Regional Development
Fund (under the projects GINOP-2.3.2-15-2016-00008 and GINOP-2.3.3-15-2016-00004). Support was also
provided by the Thematic Excellence Programme of the Ministry for Innovation and Technology of Hungary
(ED-18-1-2019-0028), within the framework of the Vehicle Industry thematic programme of the University of
Debrecen. The financial support of the Hungarian National Research, Development and Innovation Office
(FK-128333) is gratefully acknowledged.
Acknowledgments: Dedicated to P.H. Dixneuf for his outstanding contributions to organometallic chemistry and
catalysis, and for his invaluable services to the scientific community. The authors thank Attila Bényei (University
of Debrecen) for his generous recording of diffraction data and for his most useful advices. The authors are also
grateful to Éva Kováts for her invaluable help in collecting diffraction data for the highly sensitive 8 and to the
Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, for the courteous allowance to
use the diffraction equipment.
Conflicts of Interest: The authors declare no conflict of interest.
Abbreviations
Na2[Pd(HSS)] (6)
Disodium[(N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,2-diamino
Disodium[(N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,3-diaminopropano)palladate(II)]
Disodium[(N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutano)palladate(II)]
Disodium[(N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,2-diphenyl-1,2-diaminoethano)palladate(II)]
Disodium[N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,2-diamino-cyclohexano)palladate(II)];
10 was synthesized from 5a, 5b and 5c as the ligands,
Na2[Pd(PrHSS)] (7)
Na2[Pd(BuHSS)] (8)
Na2[Pd(dPhHSS)] (9)
Na2[Pd(CyHSS)] (10)
BuHSS (3)
yielding 10a, 10b and 10c, respectively
N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane
N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,2-diaminocyclohexane;
5 was synthesized from racemic
CyHSS (5)
1,2-diaminocyclohexane (5a) and from trans- and
cis-1,2- diaminocyclohexane (5b and 5c, respectively)
dPhHSS (4)
HSS (1)
N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,2-diphenyl-1,2-diaminoethane
N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,2-diaminoethane
PrHSS (2)
N,N’-bis(2-hydroxy-5-sulfonatobenzyl)-1,3-diaminopropane
References
1.
2.
3.
4.
5.
Pessoa, J.C.; Correia, I. Salan vs. salen metal complexes in catalysis and medicinal applications.
Coord. Chem. Rev. 2019, 388, 227–247. [CrossRef]
Borhade, S.R.; Waghmode, S.B. Phosphine-free Pd–salen complexes as efficient and inexpensive catalysts for
Heck and Suzuki reactions under aerobic conditions. Tetrahedron Lett. 2008, 49, 3423–3429. [CrossRef]
Henrici-Olivé, G.; Olivé, S.A. Palladium (II) complex as hydrogenase model. Angew. Chem. 1974, 13, 549–550.
[CrossRef]
Dewan, A.A. Highly efficient and inexpensive Palladium-salen complex for room temperature
Suzuki-Miyaura reaction. Bull. Korean Chem. Soc. 2014, 35, 1855–1858. [CrossRef]
Diehl, H.; Hach, C.C. Bis (N,N0-Disalicylalethylenediamine)-
µ–Aquodicobalt(II). Inorg. Synth. 1950, 3,
196–201. [CrossRef]

Molecules 2020, 25, 3993
19 of 21
6.
7.
Correia, I.; Pessoa, J.C.; Veiros, L.F.; Jakusch, T.; Dornyei, A.; Kiss, T.; Castro, M.M.C.A.; Geraldes, C.F.G.C.;
Avecilla, K. Vanadium (IV and V) complexes of Schiff bases and reduced Schiff bases derived from the
reaction of aromatic o-hydroxyaldehydes and diamines: Synthesis, characterisation and solution studies.
Eur. J. Inorg. Chem. 2005, 2005, 732–744. [CrossRef]
Pessoa, J.C.; Marc
ão, S.; Correia, I.; Gonçalves, G.; Dörnyei, Á.; Kiss, T.; Jakusch, T.; Tomaz, I.; Castro, M.M.C.A.;
Geraldes, C.F.G.C.; et al. Vanadium (IV and V) complexes of reduced Schiff bases derived from the reaction
of aromatic o-hydroxyaldehydes and diamines containing carboxyl groups. Eur. J. Inorg. Chem. 2006
,
3595–3606. [CrossRef]
8.
9.
Correia, I.; Dörnyei, Á.; Jakusch, T.; Avecilla, F.; Kiss, T.; Pessoa, J.C. Water-soluble sal2en- and
reduced sal2en-type ligands: Study of their CuII and NiII complexes in the solid state and in solution.
Eur. J. Inorg. Chem. 2006, 2819–2830. [CrossRef]
Adão, P.; Pessoa, J.C.; Henriques, R.T.; Kuznetsov, M.L.; Avecilla, F.; Maurya, M.R.; Kumar, U.; Correia, I.
Synthesis, characterization, and application of vanadium–salan complexes in oxygen transfer reactions.
Inorg. Chem. 2009, 48, 3452–3461. [CrossRef]
10. Tshuva, E.Y.; Gendeziuk, N.; Kol, M. Single-step synthesis of salans and substituted salans by Mannich
condensation. Tetrahedron Lett. 2001, 42, 6405–6407. [CrossRef]
11. Sukanya, D.; Evans, M.R.; Zeller, M.; Natarajan, K. Hydrolytic cleavage of Schiff bases by [RuCl2(DMSO)4].
Polyhedron 2007, 26, 4314–4320. [CrossRef]
12. Sippola, V.O.; Krause, A.O.I. Oxidation activity and stability of homogeneous Cobalt-sulphosalen catalyst:
Studies with a phenolic and a non-phenolic lignin model compound in aqueous alkaline medium.
J. Mol. Catal. A Chem. 2003, 194, 89–97. [CrossRef]
13. Ebrahimi, T.; Aluthge, D.C.; Patrick, B.O.; Hatzikiriakos, S.G.; Mehrkhodavandi, P. Air- and moisture-stable
Indium–salan catalysts for living multiblock PLA formation in air. ACS Catal. 2017, 7, 6413–6418. [CrossRef]
14. Ding, L.; Chu, Z.; Chen, L.; Lü, X.; Yan, B.; Song, J.; Fan, D.; Bao, F. Pd–salen and Pd–salan complexes:
Characterization and application in styrene polymerization. Inorg. Chem. Commun. 2011, 14, 573–577.
[CrossRef]
15. Maru, M.S.; Barroso, S.; Adão, P.; Alves, L.G.; Martins, A.M. New salan and salen vanadium complexes:
Syntheses and application in sulfoxidation catalysis. J. Organomet. Chem. 2018, 870, 136–144. [CrossRef]
16. Gu, X.; Zhang, Y.; Xu, Z.-J.; Che, C.-M. Iron(II)–salan complexes catalysed highly enantioselective fluorination
and hydroxylation of β-keto esters and N-Boc oxindoles. Chem. Commun. 2014, 50, 7870–7873. [CrossRef]
17. Nishihara, Y. (Ed.) Applied Cross-Coupling Reactions; Springer: Berlin, Germany, 2013.
18. Miyaura, N. Metal-Catalyzed Cross-Coupling Reactions of Organoboron Compounds with Organic Halides.
In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; De Meijere, A., Diderich, F., Eds.; Wiley-VCH: Weinheim,
Germany, 2004; pp. 41–123.
19. Beletskaya, I.P.; Alonso, F.; Tyurin, V. The Suzuki-Miyaura reaction after the Nobel Prize. Coord. Chem. Rev.
2019, 385, 137–173. [CrossRef]
20. Dixneuf, P.H.; Cadierno, V. (Eds.) Metal—Catalyzed Reactions in Water; Wiley-VCH: Weinheim, Germany, 2013.
21. Joó, F. Aqueous Organometallic Catalysis; Catalysis by Metal Complexes Vol. 23; Kluwer: Dordrecht,
The Netherlands, 2001.
22. Shaughnessy, K.H. Hydrophilic ligands and their application in aqueous-phase metal-catalyzed reactions.
Chem. Rev. 2009, 109, 643–710. [CrossRef]
23. Casalnuovo, A.L.; Calabrese, J.C. Palladium-catalyzed alkylations in aqueous media. J. Am. Chem. Soc. 1990
112, 4324–4330. [CrossRef]
,
24. Li, C.-J. Organic reactions in aqueous media with a focus on carbon carbon bond formations: A decade
−
update. Chem. Rev. 2005, 105, 3095–3166. [CrossRef]
25. Alonso, D.A.; Nájera, C. Water in organic synthesis. In Science of Synthesis; Kobayashi, S., Ed.; Thieme:
Stuttgart, Germany, 2012; pp. 535–578.
26. Mori, Y.; Kobayashi, S. Water in Organic Synthesis. In Science of Synthesis; Kobayashi, S., Ed.; Thieme:
Stuttgart, Germany, 2012; pp. 831–854.
27. Alonso, F.; Beletskaya, I.P.; Yus, M. Non-conventional methodologies for transition-metal catalysed
carbon–carbon coupling: A critical overview. Part 2: The Suzuki reaction. Tetrahedron 2008, 64, 3047–3101.
[CrossRef]

Molecules 2020, 25, 3993
20 of 21
28. Chatterjee, A.; Ward, T.R. Recent advances in the palladium catalyzed Suzuki–Miyaura cross-coupling
reaction in water. Catal. Lett. 2016, 146, 820–840. [CrossRef]
29. Shaughnessy, K.H. Greener Approaches to Cross-Coupling. In New Trends in Cross-Coupling: Theory and
Applications; Colacot, T., Ed.; The Royal Society of Chemistry: Cambridge, UK, 2015; pp. 645–696.
30. Marziale, A.N.; Jantke, D.; Faul, S.H.; Reiner, T.; Herdtweck, E.; Eppinger, J. An efficient protocol for the
Palladium-catalysed Suzuki–Miyaura cross-coupling. Green Chem. 2011, 13, 169–177. [CrossRef]
31. DeVasher, R.B.; Moore, L.R.; Shaughnessy, K.H. Aqueous-Phase, Palladium-Catalyzed Cross-Coupling
of Aryl Bromides under Mild Conditions, Using Water-Soluble, Sterically Demanding Alkylphosphines.
J. Org. Chem. 2004, 69, 7919–7927. [CrossRef] [PubMed]
32. Weeden, J.A.; Huang, R.; Galloway, K.D.; Gingrich, P.W.; Frost, B.J. The Suzuki reaction in aqueous media
promoted by P,N Ligands. Molecules 2011, 16, 6215–6231. [CrossRef]
33. Godoy, F.; Segarra, C.; Poyatos, M.; Perís, E. Palladium catalysts with Sulfonate-functionalized-NHC ligands
for Suzuki−Miyaura cross-coupling reactions in water. Organometallics 2011, 30, 684–688. [CrossRef]
34. Roy, S.; Plenio, H. Sulfonated N-Heterocyclic Carbenes for Pd-catalyzed Sonogashira and Suzuki–Miyaura
Coupling in aqueous solvents. Adv. Synth. Catal. 2010, 352, 1014–1022. [CrossRef]
35. Levin, E.; Ivry, E.; Diesendruck, C.E.; Lemcoff, N.G. Water in N-Heterocyclic Carbene-assisted catalysis.
Chem. Rev. 2015, 115, 4607–4692. [CrossRef]
36. Shahnaz, N.; Puzari, A.; Paul, B.; Das, P. Activation of Aryl Chlorides in Water for Suzuki Coupling with a
Hydrophilic Salen-Pd(II) Catalyst. Catal. Commun. 2016, 86, 55–58. [CrossRef]
37. Liu, Y.-S.; Gu, N.-N.; Liu, P.; Ma, X.-W.; Liu, Y.; Xie, J.-W.; Dai, B. Water-Soluble Salen–Pd Complex as an
Efficient Catalyst for Suzuki–Miyaura Reaction of Sterically Hindered Substrates in Pure Water. Tetrahedron
2015, 71, 7985–7989. [CrossRef]
38. Isley, N.A.; Wang, Y.; Gallou, F.; Handa, S.; Aue, D.H.; Lipshutz, B.H. A micellar catalysis strategy for
Suzuki–Miyaura cross-couplings of 2-Pyridyl MIDA boronates: No copper, in water, very mild conditions.
ACS Catal. 2017, 7, 8331–8337. [CrossRef]
39. Lipshutz, B.H.; Ghorai, S. Transitioning organic synthesis from organic solvents to water. What’s your E
factor? Green Chem. 2014, 16, 3660–3679. [CrossRef] [PubMed]
40. Handa, S.; Smith, J.D.; Hageman, M.S.; Gonzalez, M.; Lipshutz, B.H. Synergistic and selective copper/ppm
Pd-catalyzed Suzuki–Miyaura couplings: In water, mild conditions, with recycling. ACS Catal. 2016, 6,
8179–8183. [CrossRef]
41. Landstrom, E.B.; Handa, S.; Aue, D.H.; Gallou, F.; Lipshutz, B.H. EvanPhos: A ligand for ppm level
Pd-catalyzed Suzuki–Miyaura couplings in either organic solvent or water. Green Chem. 2018, 20, 3436–3443.
[CrossRef]
42. Lipshutz, B.H.; Gallou, F.; Handa, S. Evolution of solvents in organic chemistry. ACS Sustain. Chem. Eng.
2016, 4, 5838–5849. [CrossRef]
43. Gombos, R.; Nagyh
water-soluble Pd(II)-sulfosalan complex catalyst. React. Kinet. Mech. Cat. 2018, 126, 439–451. [CrossRef]
44. Voronova, K.; Purgel, M.; Udvardy, A.; B nyei, A.C.; Kath .; Jo , F. Hydrogenation and redox isomerization
ázi, B.; Joó, F. Hydrogenation of α,β-unsaturated aldehydes in aqueous media with a
é
ó
,
Á
ó
of allylic alcohols catalyzed by a new water-soluble Pd–tetrahydrosalen complex. Organometallics 2013, 32,
4391–4401. [CrossRef]
45. Lihi, N.; Bunda, S.; Udvardy, A.; Jo
and Ni(II)–sulfosalan complexes in aqueous media. J. Inorg. Biochem. 2020, 203, 110945. [CrossRef]
46. Voronova, K.; Homolya, L.; Udvardy, A.; B nyei, A.C.; Jo , F. Pd-tetrahydrosalan-type complexes as catalysts
ó, F. Coordination chemistry and catalytic applications of Pd(II)–,
é
ó
for Sonogashira couplings in water: Efficient greening of the procedure. ChemSusChem 2014, 7, 2230–2239.
[CrossRef]
47. Bunda, S.; Udvardy, A.; Voronova, K.; Joó, F. Organic solvent-free, Pd(II)-salan complex-catalyzed synthesis of
biaryls via Suzuki–Miyaura cross-coupling in water and air. J. Org. Chem. 2018, 83, 15486–15492. [CrossRef]
48. Singh, U.P.; Tomar, K.; Kashyap, S. Interconversion of host–guest components in supramolecular assemblies
of polycarboxylic acids and reduced Schiff bases. Struct. Chem. 2016, 27, 1027–1040. [CrossRef]
49. Hoshina, G.; Ohba, S.; Tsuchimoto, M. (RS,SR)-N,N0-Bis(2-hydroxybenzyl)-1,2-diphenylethylenediamine.
Acta Cryst. 1999, C55, IUC9900030. [CrossRef]
50. Cannadine, J.C.; Corden, J.P.; Errington, W.; Moore, P.; Wallbridge, M.G.H. Wallbridge Two Schiff base
ligands derived from 1,2-diaminocyclohexane. Acta Cryst. 1996, C52, 1014–1017. [CrossRef]

Molecules 2020, 25, 3993
21 of 21
51. Muthuraman, M.;
Nicoud, J.F.;
Masse, R.;
Desiraju, G.R. Crystal structure of
N,N’-di-5-nitrosalicylidene-(R,S)-l,2-cyclohexanediamine, C20H20N4O6. Z. Kristallogr.
2001, 216, 383–384. [CrossRef]
NCS
52. Bian, H.D.; Wang, J.; Wei, Y.; Tang, J.; Huang, F.P.; Yao, D.; Yu, Q.; Liang, H. Superoxide dismutase activity
studies of Mn(III)/Cu(II)/Ni(II) complexes with Schiff base ligands. Polyhedron 2015, 20, 147–153. [CrossRef]
53. Bruker. APEX3 and SAINT; Bruker AXS Inc.: Madison, WI, USA, 2017.
54. Sheldrick, G.M. SHELXT—Integrated space-group and crystal-structure determination.
Acta Crystallogr. Sect. Found. Adv. 2015, 71, 3–8. [CrossRef]
55. Sheldrick, G.M. A short history of SHELX. Acta Crystallogr. A 2008, 64, 112–122. [CrossRef]
56. Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H. OLEX2: A complete structure
solution, refinement and analysis program. J. Appl. Cryst. 2009, 42, 339–341. [CrossRef]
57. Farrugia, L.J. WinGX and ORTEP for Windows: An update. J. Appl. Cryst. 2012, 45, 849–854. [CrossRef]
58. Macrae, C.F.; Bruno, I.J.; Chisholm, J.A.; Edgington, P.R.; McCabe, P.; Pidcock, E.; Rodriguez-Monge, L.;
Taylor, R.; Streek, J.V.D.; Wood, P.A. Mercury CSD 2.0—New features for the visualization and investigation
of crystal structures. J. Appl. Cryst. 2008, 41, 466–470. [CrossRef]
59. Westrip, S.P. publCIF: Software for editing, validating and formatting crystallographic information files.
J. Appl. Crystallogr. 2010, 43, 920–925. [CrossRef]
60. Spek, A.L. checkCIF validation ALERTS: What they mean and how to respond. Acta Cryst. E 2020, 76, 1–11.
[CrossRef] [PubMed]
Sample Availability: Samples of the compounds 1–5 are available from the authors.
©
2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).