Ligand characteristics and in situ generation of Pd active species towards CC coupling using series of 2-(1H-imidazol-2-yl)phenols

Article abstract of DOI:10.1016/j.molcata.2014.02.032

Series of systematically varied 2-(1H-imidazol-2-yl)phenol ligand frameworks, which were synthesized and properly characterized, have been used to investigate favourable ligand characteristics towards in situ formation of active palladium species in Suzuk

Full text of DOI:10.1016/j.molcata.2014.02.032

Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Ligand characteristics and in situ generation of Pd active species
towards C C coupling using series of 2-(1H-imidazol-2-yl)phenols
Abiodun O. Eseolaa,b,∗, Oluwatimilehin Akoguna, Helmar Görlsb, Olubunmi Atolania,
Gabriel A. Kolawolea,c, Winfried Plassb
a Department of Chemical Sciences, Redeemer’s University, Redemption Camp, Ogun State, Nigeria
b Institut für Anorganische und Analytische Chemie, Friedrich-Schiller-Universität Jena, Humboldtstr. 8, D-07743 Jena, Germany
c Research Fellow, University of Zululand, Private Mail Bag X1001, Kwadlangezwa 3886, South Africa
a r t i c l e i n f o
a b s t r a c t
Article history:
Series of systematically varied 2-(1H-imidazol-2-yl)phenol ligand frameworks, which were synthesized
and properly characterized, have been used to investigate favourable ligand characteristics towards
in situ formation of active palladium species in Suzuki–Miyaura coupling. Structures of 2-(4,5-diethyl-1H-
imidazol-2-yl)-4-nitrophenol (p-N∼de) and 4-(tert-butyl)-2-(4,5-diphenyl-1H-imidazol-2-yl)phenol
(p-tBu∼dp) as well as the palladium complex of 2-(4,5-diethyl-1H-imidazol-2-yl)phenol (Pd.de2) were
confirmed. Structural analyses show that para-nitro-substituted phenol moieties bear poor oxo-donor
atom while the reverse was observed for para-tBu-substituted analogues. Ligand donor strengths were
also determined by pKa analysis.
Under the same reaction conditions for palladium catalyzed Suzuki–Miyaura coupling in the presence
of ‘ligand + palladium(II) acetate’ catalyst system, results show that electronic properties of the ligands are
more important than the variation in steric properties. In particular, ligands with strong bidentate chelate
coordination potentials acted as poisons while those with monodentate coordination potential proved to
be very beneficial towards in situ generation of superior active species. Furthermore, correlation between
donor strength pKa data and the trends in catalytic efficiencies as a consequence of ligand presence was
studied. Therefore, it was concluded that ligands with strong chelation tendencies adversely impacted
in situ palladium catalyst generation efficiency and that there appears to be moderate steric requirement
from ligands for optimal catalyst efficiency.
Received 5 December 2013
Received in revised form 9 February 2014
Accepted 27 February 2014
Available online 7 March 2014
Keywords:
Homogeneous catalysis
Carbon–carbon cross-coupling
In situ catalyst formation
Suzuki–Miyaura
Structure–property correlation
© 2014 Elsevier B.V. All rights reserved.
1. Introduction
Prize for Chemistry (2010) in honour of the pioneering works
of Suzuki, Heck and Negishi [11–17]. Suzuki–Miyaura catalysis,
Palladium catalyzed cross-coupling reactions are inevitable
organometallic tools for synthetic organic manipulations in the
present day molecular sciences [1–7]. Fields in molecular sciences
such as drug design, natural product total synthesis, supramolec-
ular architectural ligand designs and structure–property rela-
tionship investigations, have come to recognize the various
Pd-catalyzed C C bond forming reactions as a seamless route to
otherwise impossible organic synthetic destinations [8–10]. Recog-
nition of the importance and ease with which palladium species
accomplish C C coupling events lead to the recent award of Nobel
which is the cross-coupling of an aryl halide with boron-containing
reagents in the presence of palladium species and a base additive,
is prominently employed amongst other popular Pd-catalyzed C
C
coupling methods like Heck, Sonogashira, Stille, Negishi, Kumada,
Hiyama, etc. [18–24]. Even some notably efficient catalytic palla-
dium compounds have already been commercialized; e.g. PEPPSITM
[25].
Nearly all reported forms of palladium materials have been
implicated as active catalytic species towards C C cross-coupling
[26–28]. Hence, the true homogeneous/heterogeneous nature of
the active species has continued to be a subject of discussion
[27–30]. For instance, some recent contribution reported that
unprecedented homogeneous catalyst performance was encoun-
tered for soluble Pd(0) species bearing monodentate ligands with
sterically bulky groups (i.e. Buchwald ligands, etc.) [5,10,31,32]
∗
Corresponding author at: Department of Chemical Sciences, Redeemer’s Uni-
versity, Redemption Camp, Ogun State, Nigeria. Tel.: +234 07062192104.
E-mail addresses: bioduneseola@hotmail.com, bioduneseola@run.edu.ng
(A.O. Eseola).
while other views believe that high activities in Pd-catalyzed C
C
http://dx.doi.org/10.1016/j.molcata.2014.02.032
1381-1169/© 2014 Elsevier B.V. All rights reserved.

A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
113
mainly because, among other set-becks, there are relatively more
limitations for surface catalyst characterization unlike the possi-
bility of detailed electronic/structural characterization for discrete
drop-in homogeneous catalyst precursor systems [38–41]. In
homogeneous catalytic investigations, applying properly charac-
terized metal complex series derived from their corresponding
series of rationally varied ligand frameworks is an important
method used to pursue better understanding of the active site
formation and/or compositions as well as to study the relevant
underlying mechanisms [10,42–47]. However, such systematic
investigation involving suitable number of palladium species
derived from ligands of well studied and deliberately varied hemi-
lability trends is scarce.
In situ catalyst formation method is considered to be attrac-
tive because it obliterates necessity for the additional tasks
of prior syntheses of the corresponding palladium complexes
and it also enables the flexibility of selecting ligand types
to accompany available palladium salts depending on a spe-
cific cross-coupling catalysis requirement [43–45,48,49]. However,
investigating dependence of catalysis outcomes on ligand presence
and ligand types for in situ methods is scarce unlike studies with
preformed free or supported palladium complexes. Furthermore,
little attention is usually paid to the fact that the substrates, which
are usually present in large excess relative to catalytic amounts
of added organic ligands, may possess strongly coordinating het-
eroatoms and thus influence active site generation. It is worthy
of note that, while preformed palladium complexes would often
require some form of complex disassembly under elevated tem-
peratures in order to provide vacant coordination sites, employing
mixture of palladium salt and ligand as the catalytic system may
assemble up to similar active state configurations. Therefore, it was
considered reasonable to study effect of ligand presence and the
trends in ligand characters that would favour generation of superior
active sites while maintaining all other factors constant.
In our recent reports, experimental and DFT studies showed
that a series of 2-(1H-imidazol/oxazol-2-yl)phenol and 2-(1H-
imidazol/oxazol-2-yl)pyridine ligand families are hemilabile and
that donor intensities of the imidazole/oxazole arm of the biden-
tate ligands could vary from very poorly donating to fairly strongly
donating. The difference depends on the variation of substituent
environment around the 2-(1H-imidazol-2-yl)pyridine or 2-(1H-
imidazol-2-yl)phenol basic skeletons as well as on azole ring
heteroatom (i.e. whether the imidazole ring is replaced by oxa-
zole ring) [50–56]. Motivated by the potentials of these previously
studied ligands to shed some light on effects of ligand presence
during in situ catalyst formation towards Pd-catalyzed C C cou-
pling reactions, we herein present results for ligand syntheses and
the corresponding catalytic studies on their Pd-ligand coordination
species, which are generated in situ under similar catalytic reac-
tion condition for a series of bidentate 2-(1H-imidazol-2-yl)phenol
library. The ligands employed in this study are rationally varied in
terms of structural and electronic diversity (Scheme 1(a)–(c)). Syn-
thesis and catalytic behaviour of the palladium complex of ligand
de is also presented for comparison.
Scheme 1. (a)–(c) Ligand frameworks employed in this study (athe underlined were
synthesized according to recent reports [53–55]).
2. Experimental
cross-coupling reactions should be attributed to ligandless palla-
dium species [29,33,34]. Consequently, improved understanding of
ligand effects is necessary and is achievable by studying complexes
derived from series of rationally varied ligand framework. How-
ever, there seem to be more focus on optimizing catalyst properties
of few materials.
2.1. General considerations
All starting materials were obtained commercially as reagent
grades and used without further purification. Preparation and char-
acterization of ligands de, dp, m-M∼pt, o,p-Dm∼dp, o,p-tBu∼dp,
o,p-tBu∼pt and Bis-Im were according to published procedures
[51,53,54]. The synthesized organic compounds were either puri-
fied on silica gel column or re-crystallized to exclude impurities.
Substantial depth of study on ligand effects cannot be accom-
plishable with heterogeneously supported catalysts [33,35–37]

114
A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
Mp. 188 ◦C. Selected IR peaks (ATR, cm−1): ꢀ 3372 m (PhOH),
3223 m (imidazole proton), 2973s (ethyl), 2934s (ethyl), 1720s
(ethyl acetate C O), 1647vs (C O, C C), 1601vs (C C, C N), 1557vs
(C N, C C), 1144vs, 836vs. 1H NMR (400 MHz, TMS, CDCl3); ıppm
13.03 (s, 2H, imidazole NH), 8.80 (d, J = 2.6 Hz, 1H, phenol ring), 8.07
(dd, J = 9.2, 2.6 Hz, phenol ring), 6.97 (d, J = 9.2 Hz, 1H, phenol ring),
2.68 (q, J = 7.6 Hz, 4H, ethyl), 1.32–1.22 (m, 6H, ethyl; multiplet due
to ethyl acetate superimposition). 13C NMR (101 MHz, CDCl3); ı
171.32, 142.59, 137.47, 125.92, 121.03, 119.02, 112.14, 77.33, 77.01,
76.70, 60.47, 21.08, 18.25, 14.30, 14.19. MS (EI) m/z 261 (M+, 100%):
261, 246, 231, 215, 200. Anal Calc. for C13H15N3O3·H2O: C, 55.91;
H, 6.14; N, 15.05. Found: C, 56.12; H, 6.06; N, 15.41.
Elemental analyses were performed on Leco CHNS-932 or El Vario
III elemental analyzers. 1H and 13C NMR spectra were recorded on a
Bruker ARX 200 or 400 MHz instrument using deuterated solvents
and TMS as internal standard. IR spectra were recorded on a Nico-
let 6700 or Shimadzu 8740 FT-IR spectrometer as KBr discs and
measurements were done in the range of 4000–400 cm−1. Single
crystal X-ray data collections were carried out on a Nonius Kappa
CCD diffractometer at 133(2) K using graphite monochromated
˚
Mo-K␣ radiation (k = 0.71073 A). Cell parameters were obtained
by global refinement of the positions for all collected reflections.
The structures were solved by direct methods and refined by full-
matrix least-squares on F2. All non-hydrogen atoms were refined
anisotropically. The imidazole ring protons, the phenolic protons as
well as other protons were actually picked on the difference maps
during structure refinement. Structure solutions and refinements
were performed using the SHELX-97 package [57].
2.2.4. 2-(4,5-Dimethyl-1H-imidazol-2-yl)-4-nitrophenol
(p-N∼dm)
2-Hydroxy-5-nitrobenzaldehyde (1.67 g, 10.00 mmol), butane-
2,3-dione (0.86 g, 10.00 mmol) and ammonium acetate (≈10 g,
129.73 mmol) were reacted and purified in similar manner as for
preparation of o-tBu∼dm above to obtain p-N∼dm (0.29 g, 12%).
Dec. 139 ◦C. Selected IR peaks (KBr, cm−1): ꢀ 3070w (phenyl pro-
tons), 2926 m (methyl), 1653s (C O, C C), 1608s (C C, C N),
1552s, 752 m. 1H NMR (400 MHz, TMS, d6-DMSO); ıppm 13.83 (s,
2H, NH, phenol OH); 8.79 (d, J = 2.8 Hz, 1H, phenol ring); 8.05 (dd,
J = 2.8, 8.8 Hz, 1H, phenol ring); 6.98 (d, J = 9.6 Hz, 1H, phenol ring);
2.19 (s, 6H); trace ethylacetate. 13C NMR (100 MHz, d6-DMSO):
164.20, 141.58, 138.00, 126.17, 125.01, 120.47, 118.06, 112.58,
10.01. MS (EI) m/z 233 (M+, 100%): 233, 203, 187, 159, 28. Anal. Calc.
for C12H14N2O2·(1/10)EtAcO: C, 56.57; H, 4.91; N, 17.36%. Found:
C, 57.11; H, 4.74; N, 17.24% (see supplementary information S1).
2.2. Preparation of the ligands
2.2.1. 4-Tert-butyl-2-(4,5-dimethyl-1H-imidazol-2-yl)phenol
(p-tBu∼dm)
A
mixture of 5-tert-butyl-2-hydroxybenzaldehyde (1.70 g,
9.54 mmol), butane-2,3-dione (0.82 g, 9.54 mmol) and ammonium
acetate (≈10 g, 129.73 mmol) were refluxed in the presence of
1 mL glacial acetic acid for 1.5 h. The resulting reaction solution
was cooled, diluted with distilled water (≈30 mL), neutralized
by concentrated ammonia solution and the crude product was
extracted with dichloromethane, concentrated and purified on sil-
ica gel column using ethyl acetate/n-hexane (1:4) as eluent to
obtain p-tBu∼dm (0.41 g, 18%). Mp. 258–259 ◦C. Selected IR peaks
(KBr, cm−1): ꢀ 3244s (imidazole proton), 2958s (t-Bu and methyl),
2922 m (t-Bu and methyl), 1618s (C C or C N), 1599s (C C or
2.2.5. 2-Tert-butyl-6-(4,5-diphenyl-1H-imidazol-2-yl)phenol
(o-tBu∼dp)
C
N). 1H NMR (400 MHz, TMS, CDCl3); ıppm 7.28 (d, J = 2.0 Hz, 1H,
5-Tert-butyl-2-hydroxybenzaldehyde (1.70 g, 9.51 mmol), ben-
zil (2.00 g, 9.51 mmol) and ammonium acetate (14 g, 181.63 mmol)
were refluxed in glacial acetic acid (cc. 20 mL) for 2 h. The reac-
tion mixture was cooled, diluted with distilled water (80 mL) and
neutralized with aqueous ammonia. The crude product was fil-
tered washed with distilled water and dried. Recrystallization in
hot ethanol was carried out to obtain o-tBu∼dp (1.73 g, 51%). Mp.
204–205 ◦C. Selected IR peaks (KBr, cm−1): ꢀ 3282s (imidazole pro-
ton), 2953s (t-Bu), 1600 m (C C, C N), 1441s. 1H NMR (200 MHz,
TMS, CDCl3); ıppm 11.37 (s, 1H, NH); 7.60–7.20 (m, 12H, aromatic
H); 6.86 (d, J = 7.8 Hz, 1H); 1.47 (s, 9H, t-Bu). 13C NMR (50 MHz,
CDCl3): 128.86, 127.98, 29.59. MS (EI) m/z 368 (M+, 100%): 368,
353, 337, 177, 162. Anal. Calc. for C25H24N2O: C, 81.49; H, 6.57; N,
7.60%. Found: C, 81.53; H, 6.51; N, 7.59%.
phenol ring); 7.24 (dd, J = 2.4, 8.8 Hz, 1H, phenol ring); 6.97 (d,
J = 8.8 Hz, 1H, phenol ring); 2.23 (s, 6H); 1.32 (s, 9H, t-Bu). 13C NMR
(100 MHz, CDCl3): 154.91, 144.11, 141.19, 126.94, 118.87, 117.06,
112.17, 34.09, 31.57. MS (EI) m/z 244 (M+, 70%): 244, 229, 214, 199,
100. Anal. Calc. For C15H20N2O: C, 73.74; H, 8.25; N, 11.47%. Found:
C, 73.83; H, 8.21; N, 11.31%.
2.2.2. 4-Methoxy-2-(4,5-dimethyl-1H-imidazol-2-yl)phenol
(p-M∼dm)
2-Hydroxy-5-methoxybenzaldehyde,
(0.75 g,
4.93 mmol),
butane-2,3-dione (0.43 g, 4.99 mmol) and ammonium acetate
(≈10 g, 129.73 mmol) were reacted and purified in similar manner
as for preparation of o-tBu∼dm above using ethyl acetate/n-
hexane (1:1) as eluent. Traces of acetic acid could be observed in
the 1H NMR of the eluted compound. Therefore, the eluted product
was recrystallyzed from ethanol to obtain p-M∼dm (0.17 g, 16%).
Mp. 243–244 ◦C. Selected IR peaks (KBr, cm−1): ꢀ 3333vs(vsh,
imidazole proton), 2997 m (methyl), 2959s (methyl), 1605s (C C,
2.2.6. 3-(4,5-Diphenyl-1H-imidazol-2-yl)benzene-1,2-diol
(o-H∼dp)
A mixture of 2,3-dihydroxybenzaldehyde (0.17 g, 1.23 mmol),
benzil (0.26 g, 1.23 mmol) and ammonium acetate (1.90 g,
24.65 mmol) were reacted as for the preparation of o-tBu∼dp,
but purified using 1:4 ethyl acetate/n-hexane on silica gel col-
umn to afford o-H∼dp (0.38 g, 94%). Mp. 181–182 ◦C. Selected IR
peaks (KBr, cm−1): ꢀ 3457s(sh, PhOH), 3408s(sh, PhOH), 3217s(sh,
imidazole proton), 3055w (phenyl proton), 2984w (acetic acid),
1701vs (acetic acid), 1605 m (C C, C N), 1586w, 699s. 1H NMR
(400 MHz, TMS, d6-DMSO); ıppm 12.92 (s, 1H, NH); 12.14 (s, 1H,
phenolic OH), 8.93 (s, 1H, phenolic OH); 7.50 (m, 8H, 4,5-diphenyl);
7.34 (dd, J = 7.2 Hz, 2H, 4,5-diphenyl); 7.26 (dd, J = 7.2 Hz, 1H);
6.80 (d, J = 8.8 Hz, 1H, phenol ring); 6.74 (dd, J = 2.8 Hz, 8.8 Hz, 1H,
phenol ring); 1.91 (acetic acid). 13C NMR (100 MHz, d6-DMSO):
172.01(acetic acid), 149.62, 149.51, 145.94, 134.28, 133.75, 130.26,
128.71, 128.48, 128.20, 127.21, 127.01, 126.83, 117.62, 117.15,
112.81, 110.93, 56.01(ethanol), 21.02(acetic acid), 18.54(ethanol).
MS (EI) m/z 328 (M+, 100%): 328, 199, 271, 165. Anal. Calc. for
C
N), 739s. 1H NMR (400 MHz, TMS, d6-DMSO); ıppm 12.54 (s,
1H); 12.30 (s, 1H), 7.35 (d, J = 2.4 Hz, 1H, phenol ring); 7.12 (d,
J = 7.6 Hz, 1H, phenol ring); 6.80 (d, J = 9.2 Hz, 1H, phenol ring); 6.76
(dd, J = 2.8, 8.8 Hz, 1H, phenol ring); 3.73 (s, 3H, methoxy); 2.21 (s,
3H, methyl); 2.11 (s, 3H, methyl). 13C NMR (100 MHz, d6-DMSO):
151.74, 150.29, 143.32, 130.24, 121.86, 117.17, 115.45, 113.24,
108.10, 55.54 (methoxy), 11.77, 9.07. MS (EI) m/z 218 (M+, 98%):
218, 203, 175, 28. Anal. Calc. for C12H14N2O2·(1/4)EtOH C, 65.34;
H, 6.80; N, 12.19%. Found: C, 65.20; H, 7.12; N, 12.52%.
2.2.3. 2-(4,5-Diethyl-1H-imidazol-2-yl)-4-nitrophenol (p-N∼de)
2-Hydroxy-5-nitrobenzaldehyde (2.00 g, 11.97 mmol), hexane-
3,4-dione (1.37 g, 12.00 mmol) and ammonium acetate (18 g,
233.52 mmol) were reacted and purified in similar manner as for
preparation of o-tBu∼dm above to obtain p-N∼de (1.34 g, 43%).

A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
115
C21H16N2O2·(3/4)EtOH·(1/4)CH3COOH: C, 73.09; H, 5.73; N, 7.41%.
proton), 3086s (phenyl proton), 1641s (C O, C C), 1602vs (C C,
N), 1561vs, 1268vs, 766vs. 1H NMR (400 MHz, TMS, DMSO);
Found: C, 73.09; H, 5.56; N, 7.12% (see supporting information).
C
ıppm 9.11 (d, J = 3.0 Hz, 1H), 8.70 (d, J = 2.9 Hz, 1H), 7.63–7.52 (m,
4H), 7.48 (d, J = 6.7 Hz, 6H). 13C NMR (101 MHz, DMSO) ı 129.00,
129.00, 128.52, 128.30, 128.30, 97.70, 23.98. MS (EI) m/z 402 (M+,
100%): 402, 356, 309, 281. Anal. Calc. for C21H14N4O5: C, 62.69; H,
3.51; N, 13.92%. Found: C, 62.79; H, 3.42; N, 13.68%.
2.2.7. 2-Methoxy-6-(4,5-diphenyl-1H-imidazol-2-yl)phenol
(o-M∼dp)
2-Hydroxy-3-methoxybenzaldehyde (1.45 g, 9.51 mmol), 1,2-
diphenylethanedione (2.00 g, 9.51 mmol) and ammonium acetate
(14.76 g, 109.27 mmol) were refluxed overnight at 100 ◦C in glacial
acetic acid (60 mL). The reaction mixture was allowed to cool,
diluted with distilled water (≈100 mL) and neutralized with aque-
ous ammonia. The resulting precipitate was filtered, washed with
water and dried. The precipitate was dissolved in chloroform,
contacted with water to remove possible residues of ammonium
acetate and the organic solution was allowed to stand in order to
obtain o-M∼dp as colourless blocks of crystals (3.02 g, 93%). Mp.
196–197 ◦C. Selected IR peaks (KBr, cm−1): ꢀ 3281vs(sh) (imidazole
proton), 3057 m (phenyl proton), 2937w (methyl), 1602 m (C C,
2.2.11. 4-Nitro-2-(1H-phenanthro[9,10-d]imidazol-2-yl)phenol
(p-N∼pt)
2-Hydroxy-3,5-dinitrobenzaldehyde (2.00 g, 11.77 mmol),
phenanthrene-9,10-dione (2.49 g, 11.77 mmol) and ammonium
acetate (18 g, 233.52 mmol) were reacted in similar manner as for
preparation of o-tBu∼dm above, but the crude product was pure
enough to obtain p-N∼pt (3.68 g, 88%). Mp/Dec. 372 ◦C. Selected
IR peaks (ATR, cm−1): ꢀ 3328s (imidazole proton), 3080w (phenyl
proton), 2925w, 1611s (C C, C N). 1592vs (C C, C N), 1473vs,
1327vs, 827vs. 1H NMR (400 MHz, TMS, DMSO); ıppm 14.30 (s, 1H,
imidazole NH), 9.28 (d, J = 2.7 Hz, 1H), 8.89 (d, J = 8.2 Hz, 2H), 8.54
(d, J = 7.5 Hz, 2H), 8.25 (dd, J = 9.1, 2.7 Hz, 1H), 7.79 (t, J = 7.4 Hz, 2H),
7.71 (t, J = 7.1 Hz, 2H), 7.27 (d, J = 9.1 Hz, 1H). 13C NMR (101 MHz,
DMSO) ı 163.32, 128.62, 128.62, 127.98, 127.98, 126.63, 126.63,
124.56, 124.56, 122.49, 122.49, 104.30. MS (EI) m/z 355 (M+, 100%):
355, 325, 309, 279. Anal. Calc. for C21H13N3O3: C, 70.98; H, 3.69; N,
11.83%. Found: C, 71.09; H, 3.84; N, 11.14%.
C
N), 1594 m, 1481s, 1063s. 1H NMR (400 MHz, TMS, CDCl3); ıppm
7.55 (d, J = 6.8 Hz, 4H, 4,5-diphenyl rings); 7.51 (dd, J = 3.6, 6.0 Hz,
1H); 7.34 (m, 6H); 6.87 (m, 2H); 3.91 (s, 3H). 13C NMR (100 MHz,
CDCl3): 148.47, 146.45, 144.99, 131.58, 128.72, 128.06, 127.91,
119.23, 116.87, 112.43, 112.26, 56.20. MS (EI) m/z 342 (M+, 100%):
342, 324, 312, 299, 165. Anal. Calc. for C22H18N2O2·(2/3)CHCl3: C,
64.52; H, 4.46; N, 6.64%. Found: C, 64.37; H, 4.82; N, 6.49%.
2.2.8. 4-Bromo-2-(4,5-diphenyl-1H-imidazol-2-yl)phenol
(p-Br∼dp)
2.3. Preparation of two palladium complexes
5-Bromo-2-hydroxybenzaldehyde (1.91 g, 9.51 mmol), benzil
(2.00 g, 9.51 mmol) and ammonium acetate (12 g, 155.68 mmol)
were reacted as for o-tBu∼dp in glacial acetic acid (50 mL) to
obtain p-Br∼dp as whites microcrystalline powder (2.89 g, 78%).
Mp. 182–183 ◦C. Selected IR peaks (KBr, cm−1): ꢀ 3408 m (PhOH),
3197s (imidazole proton), 3055 m (phenyl proton), 1605s (C C,
2.3.1.
Bis-[2-(4,5-diethyl-1H-imidazol-2-yl)phenolato]palladium(II)
(Pd.de2)
Pd(AcO)2 (100 mg, 0.45 mmol) and de (190 mg, 0.89 mmol) were
stirred in EtOH (≈2 mL) at room temperature for 12 h. The precip-
itate resulting from the reaction was filtered, washed with EtOH
(≈2 mL) and dried to afford Pd.de2 as light green powder. Suit-
able single crystals for Pd.de2 were grown by slow evaporation
of solvent from its DMF solution (260 mg, 55%). Mp./Dec. > 300 ◦C.
Selected IR peaks (KBr, cm−1): ꢀ 3164 m, 3030 m, 2965s, 1620s,
1595s, 752s. 1H NMR (400 MHz, d6-DMSO): ı 11.16 (s, 1H), 7.25
(d, J = 7.6 Hz, 1H), 6.85 (t, J = 7.8 Hz, 1H), 6.67 (d, J = 8.3 Hz, 1H), 6.39
(t, J = 7.4 Hz, 1H), 3.02 (q, J = 7.4 Hz, 2H), 2.63 (q, J = 7.5 Hz, 2H), 1.23
(t, J = 7.5 Hz, 3H), 1.10 (t, J = 7.0 Hz, 3H) (see supplementary infor-
mation S2). Anal. Calc. for C26H30N4O2Pd·THF·2H2O: C, 55.86; H,
6.56; N, 8.69%. Found: C, 55.88; H, 6.39; N, 8.95%. TG analysis:
125–145 ◦C, −14.02% (tightly held solvent or water); 292–307 ◦C,
−78% (ligands).
C
N), 1580s, 1074s. 1H NMR (200 MHz, TMS, d6-DMSO); ıppm 13.14
(s, 1H); 13.08 (s, 1H), 8.30 (d, J = 2.4 Hz, 1H, phenol ring); 7.50–7.28
(m, 11H); 7.34 (d, J = 8.6 Hz, 1H, phenol ring). 13C NMR (50 MHz,
d6-DMSO): 155.82, 144.40, 134.32, 132.34, 128.74, 128.54, 128.39,
127.06, 126.87, 119.06, 114.75, 110.06, 107.38. MS (EI) m/z 390
(M+, 100%): 390, 283, 193, 165, 141. Anal. Calc. for C21H15BrN2O: C,
64.46; H, 3.86; N, 7.16%. Found: C, 64.85; H, 3.60; N, 7.27%.
2.2.9. 2-(4,5-Diphenyl-1H-imidazol-2-yl)-4-nitrophenol
(p-N∼dp)
2-Hydroxy-5-nitrobenzaldehyde (0.79 g, 4.76 mmol), 1,2-
diphenylethanedione (1.00 g, 4.76 mmol) and ammonium acetate
(7.30 g, 95.20 mmol) were treated as for o-tBu∼dp above to obtain
the spectroscopically pure ligand p-N∼dp as yellow microcrystals
in high yield (1.63 g, 95%). Mp. 259–260 ◦C. Selected IR peaks (KBr,
cm−1): ꢀ 3343s (imidazole proton), 3058 m (phenyl ring), 1597s
(C C, C N), 1581 m, 1339vs. 1H NMR (400 MHz, TMS, d6-DMSO);
ıppm ≈ 13.95 (vbr, s, 2H, NH and phenolic OH); 9.15 (s, 1H); 8.18
(d, J = 8.8 Hz, 1H); 7.54 (d, J = 8.0 Hz, 4H, 4,5-diphenyl rings); 7.44
(dd, J = 7.2 Hz, 4H, 4,5-diphenyl rings); 7.38 (dd, J = 7.2 Hz, 2H,
4,5-diphenyl rings); 7.19 (d, J = 9.2 Hz, 1H). 13C NMR (100MHz,
d6-DMSO): 143.98, 139.66, 131.37, 128.71, 128.01, 127.76, 125.57,
121.30, 111.37. MS (EI) m/z 357 (M+, 100%): 357, 327, 311, 283,
167. Anal. Calc. for C21H15N3O3·(1/3)H2O: C, 69.41; H, 4.35; N,
11.56%. Found: C, 69.54; H, 4.32; N, 11.28%.
2.3.2. Bis-[2-(4,5-dimethyl-1H-imidazol-2-yl)-4-
nitrophenolato]palladium(II)
(Pd.p-N∼dm2)
Pd(AcO)2 (53 mg, 0.24 mmol) and p-N∼dm (111 mg, 0.48 mmol)
were reacted under similar manner as for Pd.de2 to obtain Pd.p-
N∼dm2 as orange powder (70 mg, 51%). Mp./Dec. > 300 ◦C.
Selected IR peaks (KBr, cm−1):
ꢀ 3271s, 3234s, 3075 m
2929 m, 1627s, 1599s, 1487vs, 1275vs, 753s. Anal. Calc. for
C
22H20N6O6Pd·HAcO·(1/2)H2O: C, 45.05; H, 3.94; N, 13.13%.
Found: C, 44.71; H, 3.55; N, 12.84%.
2.4. Suzuki–Myaura coupling catalysis experiments
2.2.10. 2-(4,5-Diphenyl-1H-imidazol-2-yl)-4,6-dinitrophenol
(o,p-N∼dp)
In typical reactions, (4-bromophenyl)methanol (187 mg,
1.0 mmol) was reacted with 4-acetylphenylboronic acid (197 mg,
1.2 mmol) in DMF/H2O mixture (3 mL DMF + 1 mL H2O) as solvent
and in the presence of a ligand (0.4% equivalent with respect to
arylbromide), palladium(II) acetate (0.2% equivalent with respect
to arylbromide) and K2CO3 (207 mg, 1.5 mmol). Yields were
2-Hydroxy-3,5-dinitrobenzaldehyde
(0.35 g,
1.65 mmol),
hexane-3,4-dione (0.35 g, 1.65 mmol) and ammonium acetate
(2.54 g, 32.95 mmol) were reacted and purified in similar manner
as for preparation of o-tBu∼dm above to obtain o,p-N∼dp (0.62 g,
93%). Mp. 341 ◦C. Selected IR peaks (ATR, cm−1): ꢀ 3141s (imidazole

116
A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
obtained by 1H NMR experiments carried out on aliquots drawn
from the reaction solution and slowly washed by deuterated
chloroform into the NMR tube over a short bed of anhydrous
sodium sulphate after 1 h reflux duration. Amount of product
resulting from reactions were calculated by comparison of NMR
peak integration values for the methanolyl –CH2– signal on (4-
bromophenyl)methanol (the aryl-bromide substrate, ı ≈ 4.4 ppm)
with that of the biphenyl products (ı ≈ 4.7 ppm). The pure catalysis
reaction product 1-(4ꢀ-(hydroxymethyl)biphenyl-4-yl)ethanone
(1) was isolated by column chromatography purification on silica
gel and characterized by 1H NMR, 13C NMR, elemental analyses and
mass spectrometry. Analytical data of aryl-aryl coupled product is
as follows: 1H NMR (400 MHz, TMS, CDCl3); ıppm 8.01 (d, J = 8.0 Hz,
2H); 7.66 (d, J = 8.4 Hz, 2H); 7.61 (d, J = 8.4 Hz, 2H); 7.45 (d, J = 8.0 Hz,
2H); 4.75 (s, 2H, –CH2–); 2.62 (s, 3H, acetyl). 13C NMR (101 MHz,
CDCl3): 197.71 (carbonyl), 141.00, 139.23, 135.92, 128.93, 127.53,
127.45, 127.15, 64.96 (methanolyl), 26.63 (methyl). MS (EI) m/z
226 (M+, 98%): 226, 211, 165, 152. Anal. Calc. for C15H14O2: C,
79.62; H, 6.24%. Found: C, 79.52; H, 6.31%.
withdrawing effects towards the oxo-donor atom or positioned
ortho to the hydroxyl group in order to probe steric effects as well
as electronic influences. Synthetic data for these compounds are
consistent with the identity of the intended molecules [53–55]. It
is noteworthy that the 4,5-dialkyl-substituted imidazole ligands
(Scheme 1(a)) prepared from 2,3-butadione or 3,4-hexandion give
lesser yields compared to those prepared from benzil. As a result,
obtaining pure ligands for the 4,5-dialkyl-substituted imidazole
ligands attracts purification by chromatography on silica gel while
some of the 4,5-dipheny-substituted imidazole compounds give
yields that are high enough to permit only recrystallization from
suitable solvents. This observation is attributed to undesirable reac-
tion paths suffered by the 2,3-butadione or 3,4-hexandion reagent.
Occurrence of adduct solvent molecules as indicated by the
NMR, FTIR, elemental analyses and even X-ray characterization
data is a phenomenon usually observed for azole compounds
and they are often present in non-stoichiometric amounts in air-
or oven-dried samples [50–56]. In fact, it is rare to find single
crystal structures of azole-based ligands or complexes without
hydrogen-bonded solvent adducts or intermolecular networks.
This is especially so if the imidazole proton is unsubstituted. As
reported for the synthesis of ligand de, the acetic acid adduct
molecule bonded to de is so tightly held that it remains intact after
passage on silica gel during purification [53]. 1H NMR spectra of
the ligands show varying amounts of ethyl acetate, water, acetic
acid, etc., relative to ligand signals (see supplementary information
S1). Even the three crystal structures herein reported show diverse
behaviours of solvent adduct inclusion.
2.5. Experimental probe of donor strengths of imidazole N-base
and phenol oxo-atoms
Electronic donor strengths of the ligand donor atoms
were accessed via their protonation–deprotonation equilibrium
constants and the determinations were accomplished spectro-
scopically by UV–vis measurements done on Shimadzu-1600
Spectrophotometer using ∼10−5 M solutions of the ligands in
ethanol–water mixture made up of 70 mL EtOH in 100 mL standard
flasks made up to mark with 30 mL H2O. 0.74 g of KCl was added
to each 100 mL standard solution for each compound in order to
achieve a KCl concentration of 0.1 M, which is aimed at maintain-
ing a fairly constant ionic strength in the solutions. Adjusting pH
of the solutions was achieved by using KOH or HCl solutions under
constant stirring by a magnetic stirrer bar. UV measurements were
obtained for the ligand solutions under varying pH conditions rang-
ing from ∼ pH 0.5 to ∼ pH 13.5 and plots of absorbance vs pH were
made at wavelengths where pH dependent absorbance changes
were most significant. The pH of the solution was monitored using
a Crison basic 20 pH metre calibrated by buffers of pH 4.0 and 9.2.
The pKa values were extracted from inflection points of the sigmoid
fitting done to the absorption vs pH scatter with the aid of origin
software.
The ability of the explored ligands to form bis-ligated com-
plexes with palladium(II) ion in high yield has been established
through the preparation of the complex of de as representative
for comparison of catalytic outcome for active species generated
from the ‘ligand + palladium(II) salt’ approach with the catalyst
obtained from the corresponding preformed palladium complex.
ˆ
Pd(NO)2 complexes possess saturated coordination environment
with coordination number four. Therefore, prior dissociation of lig-
and donors from some of the metal coordination sites under high
temperature Suzuki–Miyaura catalytic condition is necessary to
generate active species. Thus, it is anticipated that active species
obtained during breakdown may also be built up in situ from reac-
tion of palladium(II) salt with ligands at the catalysis temperature
(Scheme 2(a)).
3.2. X-ray analyses for p-N∼de, p-tBu∼dp and Pd.de2
3. Results and discussion
Single crystal samples of p-N∼de, p-tBu∼dp and Pd.de2 suit-
able for X-ray analysis were respectively grown from their ethyl
acetate, ethanol and dimethylformamide solutions by slow evapo-
ration. Data for their structural refinement processing parameters
are presented in supplementary information Table S1. While p-
N∼de crystallizes in monoclinic Cc space group, both p-tBu∼dp
and Pd.de2 crystallize in the triclinic P-1 space group. The
observed occurrence of hydrogen-bonded solute-solvent/solute-
solute interactions in all the structures gives support to the
conclusion on presence of adduct molecules as reflected in the
analytical characterization data of the synthesized compounds
(Figs. 1–3).
3.1. Syntheses and characterization of the
2-(1H-imidazol-2-yl)phenol compounds
Several bidentate chelators were employed in this investigation
because it might aid the understanding the effect of ligand presence
and the trends in desirable ligand properties towards providing
efficient palladium active sites. As presented in Scheme 1(a)–(c),
ligands under investigation can be conveniently grouped into three
series on the basis of bulky nature; the least sterically demanding
being the 4,5-dimethyl (∼dm) and the 4,5-diethyl (∼de) members
(Scheme 1(a)) while the bis-imidazole (Bis-im) and phenan-
threneyl (∼pt) analogues (o,p-tBu∼pt, m-M∼pt and p-N∼pt)
represent the bulky/rigid ligand frameworks (Scheme 1(c)). Lig-
ands of the 2-(4,5-diphenyl-1H-imidazol-2-yl)phenol (dp) series
(Scheme 1(b)) are considered to be between these two extremes
of bulkiness/flexibility. Within each of the three groups, diversity
of electronic character was the basis for the choice of substituents.
Therefore, substituents were systematically positioned para to
the phenol hydroxyl group in order to produce electron push or
A very key observation in the structural data for p-N∼de
is the substituent-induced intramolecular proton-electron rear-
rangement. The withdrawal of O H bonding electrons towards the
nitro-substituted aryl ring leads to carbonyl double bond character
˚
of the C O bond (1.300(4) A), perturbation of the aromaticity of the
supposed phenol ring and a compensatory transfer of the phenolic
proton to the imidazole ring (Scheme 2(b)). This observation is a
direct consequence of the presence of electron withdrawing nitro-
substituent on the phenol ring of p-N∼de. Therefore, the structural

A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
117
ˆ
Scheme 2. (a) Hypothetical routs to palladium active forms via high temperature disassembly of the Pd(NO)2 complex or by assembly from ‘ligand + palladium salt’. (b)
Observed structural character induced by nitro substituent.
result for ligand p-N∼de suggests that the strength of interaction
of the ligand as anion with Pd2+ would be largely dependent on
heterocyclic imidazolate nitrogen donor and a weak or no interac-
tion from the oxo-atom; i.e. this is a display of significant tendency
for monodentate coordination based on an anionic imidazole. An
evidence for this conclusion has been seen with a para-bromo-
substituted imidazole-phenol complex in which the only remaining
coordination site on the palladium ion bonds to the imidazole nitro-
gen base while the phenol oxo donor abstains from coordination.
It is expected that the absence of strong electron-withdrawing
influence at the para-position would cause a phenolate oxygen
atom to be the anionic arm of the bidentate ligand framework while
the imidazole nitrogen base would play a complimentary neutral
donor role which could be fairly strong too. The transfer of acetic
acid proton to the imidazole nitrogen base of p-tBu∼dp (Fig. 2) and
the stability of the acetate-imidazolium product formed even after
passage over silica gel during column chromatography indicated a
fairly reliable donor strength of the imidazole nitrogen base of p-
tBu∼dp. Thus, a bidentate chelate coordination character would be
anticipated for such ligand frameworks. Furthermore, this biden-
tate character is expected to be enhanced in the presence of electron
inducing group like tert-butyl at the para-position. While the struc-
ture of p-N∼de revealed the proton-electron rearrangement as a
consequence of the presence of nitro group, structural data for the
ligand p-tBu∼dp is in accordance with a stable phenol-aromatic
electronic situation. Supplementary information Table S2 presents
summary of selected corresponding bond lengths for comparison
from p-N∼de and p-tBu∼dp. The active protons for the two lig-
ands were picked on the difference map during refinement and
not fixed. Comparing the bond lengths for the phenolic moieties
of the two ligand structures indicates that aromaticity is intact
for p-tBu∼dp while p-N∼de showed bond lengths for C(1)–C(6)
˚
(1.446(4) A) tending towards single bond character. The imidazole
bond lengths C(7)–N(1) and C(7)–N(2) are more or less equal for
p-tBu∼dp as should be expected for an imidazolium ring after
Fig. 1. Ortep plot of (a) p-N∼de.EtAcO and (b) its 1-dimensional network; thermal
ellipsoids drawn at the 50% probability level. Some atomic labels and protons have
been omitted for clarity.
Fig. 2. Ortep plot of (a) ligand p-tBu∼dp.HAcO and (b) its dimer stack enhanced by
acetic acid. Thermal ellipsoids are drawn at the 50% probability level. Some atomic
labels and protons have been omitted for clarity.

118
A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
Table 1
Estimation of catalytic turnover frequencies.
Entry
Catalyst system
Yielda (%)
TON
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Pd(AcO)2
29
17
16
35
06
52
69
90
13
06
06
33
20
22
56
46
74
32
06
74
13
145
85
80
175
30
260
345
450
65
Pd(AcO)2 + p-tBu∼dm
Pd(AcO)2 + de
Pdde2
Pd(AcO)2 + p-M∼dm
Pd(AcO)2 + p-N∼dm
Pd.p-N∼dm2
Pd(AcO)2 + p-N∼de
Pd(AcO)2 + o-tBu∼dp
Pd(AcO)2 + o,p-tBu∼dp
Pd(AcO)2 + o,p-Dm∼dp
Pd(AcO)2 + dp
30
30
166
100
110
280
230
370
160
30
Pd(AcO)2 + o-H∼dp
Pd(AcO)2 + o-M∼dp
Pd(AcO)2 + p-Br∼dp
Pd(AcO)2 + p-N∼dp
Pd(AcO)2 + o,p-N∼dp
Pd(AcO)2 + o,p-tBu∼pt
Pd(AcO)2 + m-M∼pt
Pd(AcO)2 + p-N∼pt
Pd(AcO)2 + Bis-Im
370
65
Fig. 3. Ortep plot of (a) Pd.de2 and (b) its 1D-network mediated by hydrogen-
bonded water and dmf. Thermal ellipsoids are drawn at the 50% probability level.
Some atomic labels, protons and solvent molecule have been omitted for clarity.
a
Reactions
conditions:
(4-bromophenyl)methanol
(1.0 mmol),
4-
acetylphenylboronic acid (1.2 mmol), K2CO3 (1.5 mmol), DMF/H2O solvent
mixture (3 mL DMF, 1 mL H2O), palladium(II) acetate (0.2% of arylbromide) and
ligand (0.4% of arylbromide), 1 h reflux. Yields were obtained by 1H NMR peak
integration comparison of aryl-bromide substrate (ı ≈ 4.5 ppm) and biphenyl
products (ı ≈ 4.7 ppm).
transfer of the acetic acid proton, but the difference in the bond
lengths C(7)–N(1) and C(7)–N(2) for p-N∼de is in agreement with
the suggested electron-proton rearrangement.
conditions observed in recently documented study, which involved
a series of dichloropalladium(II) complexes of neutral 2-(1H-
imidazol-2-yl)pyridines [59]. In particular, the –CH2– (methylene)
function on the (4-bromophenyl)methanol substrate enables ease
of 1H NMR tracking of substrate conversion to coupled product.
This functional group was found to be advantageous because there
is no interference around the 4.5 ppm 1H NMR region where –CH2–
group of the –CH2OH substituent gives signal [59]. Furthermore, we
have recently investigated dependence of catalytic outcomes on
varying amounts of reactants, base additives and solvents as well
as dependence on the application of varying types of base addi-
tive, arylbromides, arylboronic acids, reaction atmospheres (air
and N2), reflux durations and catalyst loadings [59]. Findings in
these recent experiments informed the basis for considering that
1.5 mole equivalent of K2CO3, dimethylformamide/water mixture
(3:1, 4 mL), arylbromide:arylboronic acid ratio of 1:1.2, catalyst
loading of 0.2 mol. % and 1hr reflux would be adequate in this
study. Yields were obtained by 1H NMR comparison of integra-
tion values for methylene (–CH2–) signal of the methanolyl group
on (4-bromophenyl)methanol (ı ≈ 4.4 ppm) with that of the cross-
coupling product (ı ≈ 4.7 ppm). Results obtained are presented in
Table 1. The choice of the applied reaction conditions is aimed to
enable discrimination in the catalytic outcomes on the bases of the
presence of different chelate frameworks.
It is noteworthy that the acetate-imidazolium association as
presented in the structure of p-tBu∼dp survived neutralization
of the acetic acid preparation medium by concentrated ammo-
nium hydroxide solution, recrystallization of its crude synthetic
product from hot ethyl acetate and growing of its single crys-
tals from ethanol. This indicates fairly strong donor strength of
its imidazole N-base. Furthermore, the observed dimerization of
the imidazolium-acetate units is aided by face-to-face ␲-stacking
˚
interactions between the aromatic rings on the ligands (∼ 3.340 A).
The R-factor of 10% for the crystal data of p-tBu∼dp came about as
a result of disordered free solvent molecules.
In the case of Pd.de2, the green crystalline needles grown from
DMF were found to contain a 1-dimentional network made possi-
ble by solvent-mediated hydrogen-bonding interactions between
bis-ligated palladium complex units. Each complex unit is held
to the next at two points via bridging water molecules, which
were observed to be bridging between the imidazole proton on
one complex and the phenolate oxygen on the next complex. DMF
molecules were also found to be hydrogen-bonded to each of these
water molecules (Fig. 3).
3.3. Investigation of influence of ligand presence in palladium
catalyzed Suzuki–Miyaura cross-coupling
The series of ligands were subjected to the catalytic
experiments under the same reaction conditions involving (4-
bromophenyl)methanol (1.0 mmol), 4-acetylphenylboronic acid
(1.2 mmol), K2CO3 (1.5 mmol), DMF/H2O solvent mixture (3 mL
DMF, 1 mL H2O), palladium(II) acetate (0.2 mol%), ligand (0.4 mol%)
and under 1 h reflux (Scheme 3). The suitability of catalytic
substrates and reaction conditions were decided based on optimum
Comparing catalytic results for the reactions in which there is
presence of one of the ligands with the reaction carried out with
only palladium acetate (Table 1, Entry 1), the turnover number
values (TON) indicate that ligands play some role in influencing
activity of the metal active centre. A key feature of the ligand
effect in the catalytic results summarized in Table 1 is that ligands
bearing electron withdrawing substituent at the para-position to
Scheme 3. The cross-coupling reaction carried out.

A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
119
with the ligands that contribute positive catalytic influence, it could
be concluded that the electronic character of the ligands hold a
higher importance above their directional properties. Relative to
catalysis results in the presence of p-N∼de, lower yields obtained
for p-N∼dm (i.e. with smaller 4,5-methyl imidazole-substituent
fragments) or p-N∼dp, o,p-N∼dp and p-N∼pt (i.e. with larger 4,5-
phenyl/phenanthrenelyl imidazole-substituent fragments) suggest
the existence of a safe magnitude of steric environments that
should be provided by the ligands around the palladium site for
increased efficiency (Table 1: Entry 8 vs Entry 6 on the one hand and
vs Entries 15, 16, 17 and 18 on the other hand). It is important to
realize that if the proposed coordination of only the imidazole part
of the favourable ligands is in effect, the phenoxo moiety will also
constitute a steric bulk around the palladium centre. Thus, further
increasing steric bulk in the 4,5-imidazole direction has produced
undesirable effects. Furthermore, the view that electronic character
is more relevant relative to steric character is supported by the fact
that the presence of the dinitro-substituted o,p-N∼dp in the cataly-
sis mixture yielded better result than for the mononitro-substituted
counterpart p-N∼dp despite that the former would suffer a more
steric effect contribution from the additional ortho-nitro- group
(Table 1: Entry 17 vs Entry 16). The planar phenanthreneyl attach-
ment to the 4,5-imidazole carbons of p-N∼pt, though more rigid,
happens to display lesser steric demands compared to its 4,5-
diphenyl analogue p-N∼dp (Table 1: Entry 20 vs Entry 16).
100
80
60
40
20
0
NO2
NH
NH
O
p-N~de
0
10
20
30
40
50
60
Time (min)
Fig. 4. Plot of yield against time for catalysis in the presence of p-N∼de.
the phenolic hydroxyl oxo-atom yielded more positive influence to
the cross-coupling reaction. In particular, higher TON values were
achieved after 1 h reflux in the presence of p-N∼de (TON = 450,
yield = 90%, Entry 7), o,p-N∼dp (TON = 370, yield = 74%, Entry 14)
and p-N∼pt (TON = 370, yield = 74%, Entry 19) compared with
result for the same catalysis reaction in the presence of only
palladium acetate as catalyst (TON = 145, yield = 29%, Entry 1). Fur-
thermore, only ligands possessing electron withdrawing functions
on the phenol ring produced yields higher than 45% within the
1 h reflux time; i.e. p-N∼dm (TON = 260, yield = 52%, Entry 6), p-
Br∼dp (TON = 280, yield = 52%, Entry 15) and p-N∼dp (TON = 230,
yield = 46%, Entry 16). Since apparent deactivation of the phenol
–OH group towards coordination appears to be favourable for the
catalysis, it may be reasonable to infer that the palladium species
possessing superior catalyst efficiencies in the investigated series
bear the ligands in a monodentate fashion involving an anionic
imidazolate donor. This view is strengthened by the fact that
electron-inducing substitution in place of the nitro- or bromo-
substituents does not only result in low yields, but also appear to
poison the palladium catalyst (Entry 1 vs Entries 2, 5, 10, 11, 18
and 19), which may be attributed to the higher bidentate chelate
character due to stronger availability of both phenolate oxo-atom
and imidazole nitrogen donors for coordination. It is worthy of
note that methoxy groups also display electron richness. In order
to examine catalytic efficiencies of active species generated by
in situ reaction of Pd(II) with representative members of the dif-
ferent electronic classes of the ligands against catalytic efficiencies
obtainable from their corresponding preformed Pd complexes,
Pd.de2 and Pd.p-N∼dm2 were employed as catalyst under similar
reaction conditions. It was observed that the preformed complex
Pd.de2 yielded higher catalytic efficiency compared to the in situ
approach, but with efficiency comparable to catalysis in the pres-
ence of only palladium acetate (Entry 3 vs Entry 4). Pd.p-N∼dm2
(TON = 345, yield = 69, Entry 7) also gave a slightly improved perfor-
mance relative to data obtained from ‘Pd(AcO)2 + p-N∼dp’ catalyst
system (TON = 260, yield = 52%, Entry 6), but the difference may not
justify a necessity for prior synthetic procedures for the complex.
In order to make a kinetic assessment of the highest performing
ligand, aliquots of reaction mixture were taken at 5 min intervals up
to 60 min for estimation of amount of product formed in the pres-
ence of palladium acetate and p-N∼de. The plot of yield against
time is presented in Fig. 4 and it shows that initial rate within the
first 10 min of the catalysis is high until about 80% yield. After-
wards, the rate reduces significantly, which may be attributed to
the large extent to which reactants have disappeared. Comparing
catalytic results on the basis of ligand steric/rigid factors especially
3.4. Experimental and theoretical probe of ligands’
electronic/donor characters
Use of UV spectroscopic method in quantifying changing con-
centrations of equilibrium species in a solution is known to render
reliable results and the ionization constants can be obtained as pKa
on the basis of Henderson–Hasselbalch equation [58]:
A − A0
pH = pKa − log
Af − A
A0 and Af represent the absorbance values at a given wavelength
when the solute molecules are totally on one side of a particular
pair of protonated–deprotonated forms for a given equilibrium.
A represents absorbance value of the protonation-deprotonation
equilibrium mixtures at the same wavelength, but under varying
pH. The pKa values were obtained from non-linear least square sig-
moid fittings on plots of pH against absorbance values at a selected
wavelength (inset of Figs. 5 and 6). R2 values are all around 99%.
Considering the protonation-deprotonation events illustrated
in Scheme 4, spectroscopic experiments were carried out to calcu-
late equilibrium constants derived as pKas in order to determine
protonation ease or otherwise for the ligands prepared during
this work. The pKas for our previously prepared ligands have been
documented [51,54] while Table 2 contains a summary of the
presently and previously estimated pKas. Examples of the spectral
stack diagrams for the investigated compounds are presented in
Figs. 4 and 5 with inset of sigmoid fittings on plots of absorbance
against pH. The pH value at the point of inflection is equal to the
pKa for a given protonation-deprotonation equilibrium. The UV
spectral stacks displayed clear isosbetic points, which shows that
spectral absorbance heights were changing only due to changes in
electronic state of solute species rather than due to overall change
in concentration of the solute ligands. Due to complicated spectral
traces, it was not possible to obtain useful pH dependent spectral
profiles for the nitro-substituted ligands p-N∼dm, p-N∼de, p-
N∼dp and o,p-N∼dp. This observation is attributed to occurrence
of more than one protonation-deprotonation equilibrium set up at
the nitro-function, which simultaneously responding to pH change
during addition of acid or base. Protonation of the imidazole N-base

120
A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
0.4
0.2
0.0
pH 1.91
pH 2.36
pH 2.87
pH 3.55
pH 4.47
pH 5.35
pH 7.54
pH 7.68
pH 8.58
0.20
0.15
2
R = 0.9985
ˆ
Scheme 4. Protonation–deprotonation equilibria for the NO ligands.
2
4
6
8
pH
was achieved by addition of acid while deprotonation of the active
protons require addition of base. Based on previous experiments
involving 2-(1H-imidazol-2-yl)pyridines [50], deprotonation of
the imidazole proton under the alkaline pH range can be ruled
out and the observed pKas in the alkaline pH experiments are
attributed to deprotonation of the phenolic –OH active proton.
The higher the pKa value for the imidazole N-base protona-
tion (pKaN:) or phenolic OH (pKaOH), the higher the donor capacity
of the N-base or phenolate lone pairs and vice versa. Literarily,
higher pKaN: for imidazole protonation implies that it is eas-
ier to saturate the imidazole N-base with protons at higher pH
rather than requiring much addition of H+ concentrations for
lower pH. On the other hand, higher pKaOH values would imply
that higher alkalinity concentration (i.e. higher pH) would be
required for detachment of corresponding hydroxyl active pro-
ton. From the results summarized in Table 2, higher pKaOH values
(hydroxyl deprotonation) observed with the t-Bu-substituted lig-
and frameworks relative to others is consistent with the conclusion
of stronger donor character of their oxo-atoms (See pKaOH for
Entries 1, 6, 7 and 15 vs other entries). Furthermore, within the
4,5-diphenyl-imidazole series, their pKaOH values reduced as elec-
tron inducing strength of the phenol ring substituents reduced;
o,p-tBu∼dp [13.47 ( 0.02)] ≈ p-tBu∼dp [≥13.32 ( 0.14)] > o,p-
Dm∼dp [≥11.64 ( 0.09)] > dp [≥10.05 ( 0.08)]. Therefore, the
agreement between higher pKaOH values (i.e. strong oxo-donor
strengths) and the corresponding low yields or catalyst poisoning
behaviours support the thinking that strong bidentate chelation
NH
OH
OH
N
250
300
350
Wavelength (nm)
Fig. 5. Spectral overlays for o−H∼dp in the acidic pH range showing isosbetic
points; inset is sigmoid plot of absorbance vs pH.
0.4
pH 7.05
Table 2
pH 8.42
Experimentally estimated acid/base strengths of the imidazole ligand derivatives
0.2
(obtained as pKas).a
pH 8.62
2
R
= 0.9986
pH 10.37
pH 11.11
pH 12.11
pH 12.61
pH 12.99
pH 13.19
Entry
Ligands
Free ligand deprotonation constantsg
pKaN:
(
S)b
pKaOH
>14.00c
( S)
0.1
8
10
pH
12
f
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
p-tBu∼dm
de
–
6.64 ( 0.07)d
6.62 ( 0.15)
11.91 ( 0.10)d
12.26 ( 0.07)
p-M∼dm
p-N∼dm
p-N∼de
o-tBu∼dp
o,p-tBu∼dp
o,p-Dm∼dp
dp
f
f
–
–
–
f
f
–
≤2.01 ( 0.05)c
2.28 ( 0.04)d
3.38 ( 0.07)d
4.22 ( 0.10)d
4.02 ( 0.03)
3.54 ( 0.05)
3.27 ( 0.11)
≥13.32 ( 0.14)c
13.47 ( 0.02)d
11.64 ( 0.09)d
10.05 ( 0.08)d
10.18 ( 0.02)
11.69 ( 0.06)
10.36 ( 0.05)
0.2
O
NH
OH
N
o-H∼dp
o-M∼dp
p-Br∼dp
p-N∼dp
o,p-N∼dp
o,p-tBu∼pt
m-M∼pte
p-N∼pt
f
f
–
–
–
–
f
f
1.11 ( 0.02)d
13.04 ( 0.08)d
3.37 ( 0.03)e
11.33 ( 0.11)e
f
f
–
–
Bis-Im
Not done
Not done
a
Obtained spectroscopically.
S represents standards errors.
These are approximate pKas since their sigmoid fittings are non-symmetrical
b
c
for extreme of pH data.
0.0
d
Data according to Ref. [42].
Data according to Ref. [45].
Complicated spectral profile at various pH prevented calculation of pKas.
The pKa data were determined in an independent experiment and not in the
300
400
e
Wavelength (nm)
f
g
Fig. 6. Spectral overlays for o−M∼dp under alkaline pH showing isosbetic points;
inset are sigmoid plot of absorbance vs pH.
presence of palladium acetate.

A.O. Eseola et al. / Journal of Molecular Catalysis A: Chemical 387 (2014) 112–122
121
adversely affected the palladium efficiency and that monodentate
Acknowledgements
imidazolate coordination in the presence of poor donor oxo-atoms
is proposed to be beneficial for the cross-coupling event. The pKaN:
values pertaining to the imidazole base donor strength did not give
a clear trend in correlation with catalytic role of the ligands, but
the crystal data for the diethyl- and dephenyl-ligands presented
above suggests that the imidazole donor strengths are generally
fairly strong regardless of 4,5-imidazole substitution.
A.O.E is grateful to the Redeemer’s University Research Grants
Committee for supports towards purchase of some laboratory facil-
ities. The authors are also thankful for generous grants from the
Deutsche Forschungsgemeinschaft (DFG: PL 155/9, PL 155/11, and
PL 155/12).
DFT calculations using B3LPY/6311+G* were carried out to
optimize the geometries of all studied ligands under simulated
water/ethanol dielectric constant in effort to further pursue under-
standing of the peculiar characteristics common to the ligands
that displayed favourable ligand effects towards in situ genera-
tion of active species. Unfortunately, there was no clear correlation
between experimentally observed trends and the theoretically
derived Mullekan charges on the ligand donor atoms. Thus, the data
is not presented.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.molcata.
2014.02.032.
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