Revealing the unusual role of bases in activation/deactivation of catalytic systems: O-NHC coupling in M/NHC catalysis

Article abstract of DOI:10.1039/c8sc01353e

Numerous reactions are catalyzed by complexes of metals (M) with N-heterocyclic carbene (NHC) ligands, typically in the presence of oxygen bases, which significantly shape the performance. It is generally accepted that bases are required for either substrate activation (exemplified by transmetallation in the Suzuki cross-coupling), or HX capture (e.g. in a variety of C-C and C-heteroatom couplings, the Heck reaction, C-H functionalization, heterocyclizations, etc.). This study gives insights into the behavior of M(ii)/NHC (M = Pd, Pt, Ni) complexes in solution under the action of bases conventionally engaged in catalysis (KOH, NaOH, t-BuOK, Cs₂CO₃, K₂CO₃, etc.). A previously unaddressed transformation of M(ii)/NHC complexes under conditions of typical base-mediated M/NHC catalyzed reactions is disclosed. Pd(ii) and Pt(ii) complexes widely used in catalysis react with the bases to give M(0) species and 2(5)-oxo-substituted azoles via an O-NHC coupling mechanism. Ni(NHC)₂X₂ complexes hydrolyze in the presence of aqueous potassium hydroxide, and undergo the same O-NHC coupling to give azolones and metallic nickel under the action of t-BuOK under anhydrous conditions. The study reveals a new role of NHC ligands as intramolecular reducing agents for the transformation of M(ii) into ligandless M(0) species. This demonstrates that the disclosed base-mediated O-NHC coupling reaction is integrated into the catalytic M/NHC systems and can define the mechanism of catalysis (molecular M/NHC vs. NHC-free cocktail-type catalysis). A proposed mechanism of the revealed transformation includes NHC-OR reductive elimination, as implied by a series of mechanistic studies including ¹⁸O labeling experiments.

Full text of DOI:10.1039/c8sc01353e

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Revealing the unusual role of bases in activation/
deactivation of catalytic systems: O–NHC coupling
in M/NHC catalysis†
Cite this: DOI: 10.1039/c8sc01353e
Victor M. Chernyshev,a Oleg V. Khazipov,a Maxim A. Shevchenko,a
b
Andrey Yu. Chernenko,a Alexander V. Astakhov,a Dmitry B. Eremin,
Dmitry V. Pasyukov,a Alexey S. Kashinb and Valentine P. Ananikov
*
ab
Numerous reactions are catalyzed by complexes of metals (M) with N-heterocyclic carbene (NHC) ligands,
typically in the presence of oxygen bases, which significantly shape the performance. It is generally
accepted that bases are required for either substrate activation (exemplified by transmetallation in the
Suzuki cross-coupling), or HX capture (e.g. in a variety of C–C and C-heteroatom couplings, the Heck
reaction, C–H functionalization, heterocyclizations, etc.). This study gives insights into the behavior of
M(II)/NHC (M ¼ Pd, Pt, Ni) complexes in solution under the action of bases conventionally engaged in
catalysis (KOH, NaOH, t-BuOK, Cs2CO3, K2CO3, etc.). A previously unaddressed transformation of
M(II)/NHC complexes under conditions of typical base-mediated M/NHC catalyzed reactions is disclosed.
Pd(II) and Pt(II) complexes widely used in catalysis react with the bases to give M(0) species and 2(5)-oxo-
substituted azoles via an O–NHC coupling mechanism. Ni(NHC)2X2 complexes hydrolyze in the
presence of aqueous potassium hydroxide, and undergo the same O–NHC coupling to give azolones
and metallic nickel under the action of t-BuOK under anhydrous conditions. The study reveals a new
role of NHC ligands as intramolecular reducing agents for the transformation of M(II) into “ligandless”
M(0) species. This demonstrates that the disclosed base-mediated O–NHC coupling reaction is
integrated into the catalytic M/NHC systems and can define the mechanism of catalysis (molecular
M/NHC vs. “NHC-free” cocktail-type catalysis). A proposed mechanism of the revealed transformation
includes NHC-OR reductive elimination, as implied by a series of mechanistic studies including 18O
labeling experiments.
Received 23rd March 2018
Accepted 19th May 2018
DOI: 10.1039/c8sc01353e
rsc.li/chemical-science
complexes in catalysis is attributed to the great stability of M–
NHC bonds and the high variability of the steric and electronic
Introduction
parameters of NHC ligands, which allows effective tuning of the
catalyst activity.1,3
Complexes of transition metals with N-heterocyclic carbene
(NHC) ligands are commonly applied as catalysts for a variety of
C–C and C-heteroatom bond formations, C–H functionaliza-
tions, the Mizoroki–Heck reaction, atom-economic additions,
and many other transformations.1 Fine organic synthesis and
its industrial applications are indispensable for obtaining
complex molecular structures of pharmaceutical substances,
natural product substitutes, smart materials, and molecular
electronic components, among many other examples of para-
mount signicance.2 The universal application of M/NHC
The vast majority of practically relevant M/NHC catalyzed
reactions are conducted in the presence of bases, including
strong bases like alkali metal hydroxides or alkoxides.1–5 The
bases play important roles of capturing HX from the catalytic
cycle, facilitating the transmetallation process, and inducing
the formation of nucleophilic reagents.4b,6 The nature of the
base can signicantly shape the catalytic performance of the M/
NHC system in terms of activity and selectivity.1–7
Several published studies of catalytic systems consider the
effects of the base on the metal center of the catalyst and reveal
few additional roles of bases in metal-catalyzed reactions.
Participation of bases in ligand exchange, with its effects on the
activity and selectivity, is a well-established phenomenon. For
example, coordination of tert-butoxide anions to nickel
promotes the oxidative addition of H2 in C–O activation reac-
tions.8 Coordination of tertiary amines apparently blocks the b-
hydride elimination in the Mizoroki–Heck reaction, and this
aPlatov South-Russian State Polytechnic University (NPI), Prosveschenya 132,
Novocherkassk, 346428, Russia
bZelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky
Prospect 47, Moscow, 119991, Russia. E-mail: val@ioc.ac.ru
† Electronic supplementary information (ESI) available: Additional experimental
data for reaction mechanisms and stoichiometry, copies of NMR spectra and
Raman spectra, GC-MS and ESI-MS data, and FE-SEM/EDS data. See DOI:
10.1039/c8sc01353e
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place in a number of already known catalytic systems;5 however,
it was not reported previously.
A new base-mediated reaction of O–NHC coupling is
discovered, leading to “NHC-free” metal species and azolones
(Scheme 1) under conditions typical for M/NHC catalyzed
reactions. By virtue of the O–NHC coupling, NHC ligands act as
intrinsic reducing agents to produce M(0) species. “Ligandless”
metal species are renowned for their high chemical activity and
outstanding catalytic performance. The revealed O–NHC
coupling reaction can occupy a dominant place in the whole
process by controlling the generation of active centers or initi-
ating deactivation of a catalytic system, depending on particular
catalytic mechanisms.
Scheme 1 Discovered O–NHC coupling reactions in M/NHC systems.
explains why the replacement of CsOPiv bases by Bu3N switches
the reaction toward Michael addition.7c Yet another important
role of bases, the catalyst activation via reduction of M(+)L
complexes to active M(0)L molecular complexes, should be
considered. In this type of catalyst activation, bases like alco-
holates or amines can act as either direct reductants via hydride
transfer,4a,9 or promoters of reductive elimination of the
“leaving” p-coordinated allyl ligands via nucleophilic addition
to the allyl p-system.10
Results and discussion
Transformations of M/NHC complexes under the action of
bases
A variety of NHC ligands (16 examples) and M/NHC complexes
of Pd, Pt, Ni (25 examples) were tested to estimate the scope of
the revealed reaction (Scheme 2). A set of typical bases including
KOH, NaOH, K2CO3, Cs2CO3, t-BuOK, and t-BuONa were
employed in these experiments (Table S1†). Solvents, tempera-
tures and reaction times (40–140 C, 3–24 h) used here corre-
spond to typical reaction conditions used for a variety of
reported catalytic reactions.1–4,6,7,13
For all of the bases, decomposition of the metal complexes
leading to precipitation of agglomerated M(0) nanoparticles (M
¼ Pd, Pt, Ni) or Ni(OH)2 was observed. Compositions and
structures of the metal precipitates were determined by X-ray
uorescence spectroscopy (XRF), eld-emission scanning elec-
tron microscopy (FE-SEM, Fig. 1 and ESI†), and Raman
spectroscopy.
Reactions of complexes 2–6 with bases can be divided into
three different types depending on the main reaction product
structures (Scheme 3). Plausible stoichiometry for the reactions
is presented in Scheme S2.†
Within the framework of the current concept, the M/NHC
core is thought to confer the catalytic activity, whereas the
bases are thought to be responsible for the chemical versatility.
Boosts of catalytic performance observed with M/NHC
complexes are typically attributed to ligand effects on the
chemical transformation studied or optimization of reaction
conditions. Recently, the ability of aliphatic amine bases to
induce cleavage of M–NHC bonds with the fast release of cata-
lytically active NHC-free metal species has been reported.11
Decomposition of M/NHC complexes in the presence of strong
bases was reported in a few cases.12 However, activation/
deactivation of M/NHC complexes with bases, which would
cause transformations of NHC ligands and affect the M–NHC
bonds, remain understudied.
ꢀ
In the present work, we reveal a transformation of M/NHC (M
¼ Pd, Pt, Ni) complexes taking place in the presence of most
widely applied bases, such as KOH, NaOH, t-BuOK, Cs2CO3,
K2CO3, etc. The transformation reported here actually may take
Scheme 2 Overview of the ligand precursors (1) and metal complexes (2–6) utilized in the present study.
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halogen-bridged complex 3 were the most reactive, bis-NHC Pd
complexes 4 were signicantly less reactive, and Pt complexes 5
and Ni complexes 6 were the least reactive (Table S1†). Notably,
the reaction proceeded even at 40 ꢀC and was accelerated upon
heating (see variable temperature experiments, Fig. S1†). As an
illustration, compound 2a was converted almost completely
within ꢁ20 min when heated with t-BuOK in dioxane at 100 ꢀC
to give benzimidazolone 7a in ꢁ80% yield, while it required 3 h
for complexes 4a and b to give good yields of azolones 7a and c
(86–87%) (Table S1†). Even more, promoting the reaction with
Pt complexes 5a and b and Ni complexes 6a and b required
heating for ꢁ20 h and ꢁ48 h, respectively.
Concerning the possible inuence of the structure of NHC
ligands, metal complexes with bulky substituents, especially
DiPP and Mes (compounds 2j–m), reacted somewhat slower.
The yields of azolones 7 dramatically depended on the hetero-
cycle type of the NHC ligands. The highest yields of azolones 7
were obtained for complexes 2a–i, 3, 4a and b, 5a and b, and 6a
and b with NHC ligands of benzimidazole type, which formed
stable benzimidazol-2-ones 7a–h. For complexes 2j–r
comprising NHC ligands of imidazole and 1,2,4-triazole series
(except the 2j–m complexes with bulky substituted N,N0-aryl-
imidazoles), only trace yields of the corresponding azolones
7k–o were detected by GC-MS (see ESI†). Low yields of imidazol-
2-ones and triazol-5-ones were related to their instability and
solvolysis (discussed below in more detail).
By comparing the effects of different bases on 2a–i Pd
complexes it could be noticed that stronger bases like t-BuOK, t-
BuONa, KOH, and NaOH provided higher reaction rates and
higher benzimidazol-2-ones yields (43–97%) than mild and less
soluble K2CO3 and Cs2CO3 (ꢁ0–57%) (Table S1†). Remarkably,
Pt complexes 5a and b were almost unreactive toward KOH in
Fig. 1 FE-SEM images of palladium (a) and platinum (b) precipitates
isolated from reaction mixtures after heating complex 2a with KOH in
pyridine at 100 ꢀC for 24 h and complex 5a with t-BuOK in 1,4-dioxane dioxane within 20 h, while they afforded 42% and 65% HPLC
at 100 ꢀC for 20 h, respectively.
yields of azolones 7a and d with t-BuOK under the same
conditions (Table S1†). The Type 3 reaction observed for
complex 6a, heated with aqueous KOH in dioxane, may be
Type 1 reactions involved palladium complexes 2 and 3 and
platinum complexes 5a and b to yield free metal particles of
Pd(0) and Pt(0) (Fig. 1) and azolones 7a–o with all of the bases
(Scheme 3, Table S1†).
Type 2 reactions were observed for bis-NHC complexes 4a
and b and 6a and b. Heating complexes 4a and b with KOH and
t-BuOK, and heating complexes 6a and b with t-BuOK resulted
in formation of Pd(0) and Ni(0) precipitates, correspondingly,
and azolones 7a, c and f (quantitatively detected as 1 mol per
mole of the initial complex) as the main products. However,
diamines 8a–c were also detected by HPLC and GC-MS in the
reaction mixtures (Scheme 3, Table S1†).
considered as a fresh example of Ni–NHC hydrolysis (see a more
detailed discussion below).14
Yields of azolone 7a in the reaction between complex 2a and
t-BuOK in 2-propanol (62%) and DMF (58%) were lower than
those in dioxane (91%) and pyridine (95%) (Table S1†). The
lower yields may be explained by concurrent partial reduction of
Pd(II)NHC to Pd(0) species and azolium salts/NHC in these
solvents.15 Azolium salts and NHCs subsequently undergo
solvolysis to form diaminobenzenes (see discussion below).
Mechanistic study of azolone formation
A Type 3 reaction was observed for nickel complex 6a, which
transformed into Ni(OH)2 and diamine 8a when heated with
aqueous KOH in dioxane (Scheme 3). Only trace amounts of 1,3-
dimethylbenzimidazolone 7a (yields up to 9%) were detected by
HPLC and GC-MS in the reaction mixture.
The main product yields strongly depended on the structure
of the initial complex, the base, and the solvent. Comparing the
reactivities of the complexes toward t-BuOK in Type 1 and Type
2 reactions, it could be concluded that Pd complexes 2 and the
Consideration of the results raises a question: what pathways
lead from the metal complexes to azolones in the presence of
strong oxygen bases? It should be noted that azolium salts 1
heated with KOH and t-BuOK under the conditions that favor
decomposition of complexes 2–6 produce quite low yields of
azolones (#10%), probably via the disproportionation reac-
tion.16 This result makes it impossible to explain the high yields
of azolones 7 by simple solvolysis of complexes 2–6 and
subsequent disproportionation of azolium salts.
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Scheme 3 Reactions of M/NHC complexes with KOH (Conditions A) and t-BuOK (Conditions B). HPLC and isolated (blue color) yields are shown
for each case. HPLC/isolated yields are calculated assuming that, theoretically, 1 mole of azolone 7a, c, and f is formed from 1 mole of the
complex 4a and b, and 6a and b. Conditions A: KOH, H2O, pyridine, 100 ꢀC; Conditions B: t-BuOK, 1,4-dioxane, 100 ꢀC. For additional details and
other reaction conditions see the Experimental section, Table S1 and Fig. S1.†
To evaluate the formation of azolones 7 directly in the directly in the course of metal-catalyzed reactions.17 A solution
reaction of M/NHC complexes with bases rather than during the of a particular complex in THF was heated at 100 ꢀC with
isolation procedures or preparation of analytic samples, we continuous transfusing to a mass spectrometer. Aer ꢁ1 min,
performed ESI-MS online monitoring of the reaction for an aqueous solution of KOH (or a suspension of t-BuOK in THF)
a selection of complexes, 2a, b, o, and r, and 4a (Fig. S2–S11†). was injected into the reaction mixture, initiating almost
ESI-MS online monitoring is a powerful method for detecting immediate appearance of the corresponding azolone 7a, b, l, or
charged or ionizable reactants, intermediates, and products o (details in the ESI†). To corroborate that the base was the
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source of oxygen, we also carried out isotope experiments with
18O labeled KOH. Indeed, ESI-MS online monitoring of the
reaction between the compound 2a and a solution of KOH in
H218O (97% of 18O in the aqueous solution) revealed the
formation of 18O azolone 7a (Fig. 2). The reaction was also
performed preparatively in pyridine using a solution of potas-
sium in H218O. The azolone 7a-[18O] was obtained in 47% iso-
lated yield (Scheme 4). The possibility of isotope exchange in the
product under reaction conditions was rejected by conducting
a corresponding control experiment with isolated 7a-[16O] and
K18OHaq (see ESI for details†). Eventually, the ESI-MS online
monitoring and isotope experiments unambiguously conrmed
the direct formation of azolones 7 in the reaction between
M/NHC complexes and oxygen bases.
Thus, the experiments clearly revealed a previously unde-
scribed O–NHC coupling reaction resulting from the action of
strong oxygen bases on the M/NHC complexes (Scheme 5). The
assumed stoichiometries for various combinations of M/NHC
complexes and bases are presented in Scheme S2.† In this
reaction, NHC ligands play a previously undiscussed role of
metal reductants, transforming M(II) into M(0) with the forma-
tion of azolones 7 as oxidized derivatives of NHC.
The most probable mechanism of this reaction, in our
opinion, includes a reversible exchange of ligand L (or X) by
ROꢂ with subsequent C–O cross-coupling of M-coordinated
NHC and ROꢂ accompanied by the reductive elimination of
M(0) species (“Reductive elimination” mechanism, Scheme 5).
Indeed, ESI-MS online monitoring of the reaction between 4a
and KOH in THF revealed the formation of intermediate
hydroxy-complex 9 (in the [M + K]+ form) (Scheme 6, Fig. S4†).
Similar intermediate complexes were observed in reactions of
other Pd–NHC complexes with KOH. Collision-induced disso-
ciation tandem mass spectrometry (MS/MS) applied to the ion 9
suggests the direct formation of azolone 7a from 9 as a major
fragmentation pathway (Scheme 6, Fig. S5†). Similar mecha-
nisms of C–C and C–H cross-couplings of NHC have been
previously presented as the most probable pathways of deteri-
oration of M/NHC complexes in the course of catalytic
reactions.18
Scheme 4 Reaction of complex 2a with K18OH.
Yet, an alternative mechanism of azolone formation may
include direct nucleophilic attack of ROꢂ on the C(carbene) atom
of M-coordinated NHC with subsequent dissociation of M–C
bonds accompanied by elimination of M(0) species (“Nucleo-
philic” mechanism, Scheme 5). However, direct nucleophilic
attack on the carbene atom of NHC ligands coordinated with
metal M should be sterically hindered by bulky N-substituents
of the NHC-ligand and M-coordinated co-ligands X and L.
Therefore, we think that the “nucleophilic” mechanism is less
probable. We also cannot exclude a completely different
mechanism of the oxidation of electron rich [NHC-OR]ꢂ anions
by M(II) species. The anions may be formed from dissociation of
M–NHC bonds and reversible addition of ROꢂ to the released
NHC. Despite the strongly nucleophilic character of NHCs,
some examples of their electrophilic behavior can be found in
the literature.19 The structures of azolones 7 are conrmed by
1H, 13C NMR, and ESI-MS spectra.
Mechanistic study of diamines and other cleavage product
formation
Formation of diaminobenzenes 8 from bis-NHC complexes 4a
and b, and 6a and b in the course of Type 2 reactions may be
Fig. 2 Real-time abundances of 7a-[18O] and 7a-[16O] (in ionic [M +
K]+ form) in the reaction between complex 2a and K18OHaq in THF at
100 ꢀC. Solution of KOH in H218O was added after 1.2 min of recording.
Scheme 5 Plausible mechanisms of the oxygen base-mediated O–
NHC coupling of M/NHC complexes.
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Scheme 8 Reaction of complex 6a with KOH.
Scheme 6 Formation of hydroxy-complex 9 and its transformation
into azolone 7a during the reaction of complex 4a with KOH (ESI-MS
online and MS/MS experiments).
Scheme 9. Pd/NHC complex 2j which is frequently used in
catalysis was selected as a precatalyst for the reactions (1)–(3).
The reactions (1)–(3) were performed in two distinct
manners, methods A and B (Scheme 9). In the method A, freshly
prepared solution of the complex 2j in pyridine was used as the
catalyst. In the method B, the precatalyst 2j was heated with t-
BuOK in pyridine, neutralized by pyridine hydrochloride, and
the solution obtained was introduced to the reaction mixtures
(see the Experimental part for details). It is important to note
that decomposition of the complex 2j to give azolone 7i in the
course of the pretreatment (method B) was conrmed by GC-
MS. The obtained experimental data are shown in Scheme 9.
In the Mizoroki–Heck reaction (1) performed without initial
pre-activation (method A), complex 2j was almost inactive, only
a minor yield of the product 12 was observed. However, in the
experiment with the t-BuOK pretreatment (method B), the
catalytic activity of the precatalyst solution was signicantly
higher. Thus, in the Mizoroki–Heck reaction (1), O–NHC
coupling leads to activation of the Pd/NHC catalyst, apparently
explained by a transformation shown in Scheme 7. At the rst
stage, O–NHC coupling with a base gives an azolone (1 mol per
mole of M(NHC)2X2) and a NHC (in equilibrium with its
protonated form, i.e. azolium cation). At the second stage, the
released NHC undergoes solvolysis to give diamine 8 under
strongly basic conditions via the known reaction mechanism
(Schemes 7 and S1, and details in the ESI†).16
Reaction of nickel complex 6a with aqueous KOH giving
Ni(OH)2 and diamine 8a (Scheme 8) could be predicted from
previously published data on facile hydrolysis of Ni/NHC
complexes producing azolium salts and Ni(OH)2 in the presence
of water.14 Benzimidazolium salt 1a, the intermediate product
of the reaction, undergoes solvolysis to diamine 8a.16 The
solvolysis is accompanied by the formation of small amounts
(ꢁ9% HPLC yield) of azolone 7a via the parallel dispropor-
tionation mechanism (Scheme S1 and discussion in the ESI†).16
To check the proposed schemes of the formation of
diamines 8 from benzimidazolium salts, a model reaction of
azolium salts 1a, c, and f with t-BuOK in 1,4-dioxane was
examined. Diamines 8a–c (82–85% HPLC yields) and azolones
7a, c, and f (8–10% HPLC yields) were the major products, in full
compliance with the proposed schemes.
Possible impacts of the revealed base effect on catalytic
reactions
The three different reactions chosen to investigate the impact of
the revealed O–NHC coupling on catalytic performance were:
the Mizoroki–Heck reaction (1), the Suzuki–Miyaura cross-
coupling (2), and C–H functionalization (3) as shown in
Scheme 9 Possible impacts of O–NHC coupling on Pd-catalyzed
C–C coupling reactions. (a) Pretreatment of the catalyst with t-BuOK
for 10 min at 100 ꢀC. (b) Pretreatment of the catalyst with t-BuOK for
3 h at 100 ꢀC.
Scheme 7 Formation of diamines 8 from complexes 4 and 6.
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by promoting the formation of “NHC-free” Pd active species. BuOK, or alkali metal carbonates. In such systems, NHC ligands
High performances in cocktail-type systems is a distinctive play a role in the reduction of M(II) to M(0) by means of the O–
feature of the Mizoroki–Heck reaction.18c,20 Removal of the NHC NHC coupling reaction affording “NHC-free” M(0) active species
ligands favours generation of a cocktail-type system and facili- and azolones.
tates the product formation.
In the Suzuki–Miyaura reaction (2), formation of product 14
was observed in both cases. Since transmetallation usually
Conclusions
represents a rate-limiting step of this cross-coupling reaction,
Complexes of metals with N-heterocyclic carbenes, M(NHC)X2L
M/NHC catalytic species and ligand-free cocktail-type systems
[M ¼ Pd(II), Pt(II), Ni(II)], react with oxygen bases typically
may show similar performances. Although it affects the
applied in various catalytic processes to give M(0) nanoparticles
formation of “NHC-free” metal species in solution, O–NHC
and azol-2(5)-ones. In this previously undescribed O–NHC
coupling has no determining effect on the outcomes of the
coupling reaction, NHC ligands play the role of two-electron
Suzuki–Miyaura reaction.
intramolecular reductants of the coordinated metal dications.
In the C–H arylation reaction (3) carried out in the presence
The base anions serve as a source of oxygen. The azol-2(5)-ones
of t-BuOK, only a fresh solution of the complex 2j was fairly
forming from the NHC of imidazole and 1,2,4-triazole series are
active (Scheme 9). The catalytic solution obtained aer the t-
labile compounds that decompose with the destruction of
BuOK pretreatment (method B) was less active, and its activity
heterocycles.
signicantly decreased with prolongation of the pretreatment
Among Pd(II), Pt(II), and Ni(II) complexes examined in this
time from 10 min to 3 h. Formation of azolone 7i due to slow
work, Pd complexes are found to be the most reactive and thus
decomposition of 2j in the course of the reaction (method A)
more prone to the O–NHC coupling. A combination of Pd with
was also detected by GC-MS. Thus, in the C–H functionalization
NHC ligands gives a exible catalytic system, whose nature can
reaction (3) O–NHC coupling causes deactivation of Pd/NHC
be tuned from the Pd/NHC to “NHC-free” molecular or cluster/
catalytic systems. The results suggest that Pd/NHC are catalyt-
nanoparticle catalysis.
ically active species, while ligand-free or cocktail-type systems
The base-mediated O–NHC coupling has a signicant impact
are less efficient or inactive.
on the performance of the M/NHC catalytic systems. On one
The results outlined in Scheme 9 clearly corroborate the
hand, the reaction provokes deactivation of these catalytic
importance of the base-mediated O–NHC coupling for the
systems, where participation of molecular M/NHC complexes in
catalytic activity of M/NHC complexes. Base-mediated M–NHC
the transition state of a catalytic reaction is essential, like in the
bond cleavage revealed in the current study can largely deter-
chiral NHC–metal-based asymmetric catalysis. Certainly, O–
mine the behavior of catalytically active metal species.
NHC coupling should be a problem for homogeneous M/NHC
On the one hand, the O–NHC coupling reaction can provoke
catalysis when highly active palladium complexes and strong
decomposition of M/NHC complexes and thus accelerate
bases like alkali metal alcoholates or hydroxides are applied.
deactivation of catalytic systems where only molecular M/NHC
The present study clearly demonstrates that the suppression of
complexes are capable of driving the catalytic cycle (classical
O–NHC coupling is an important, overlooked priority in main-
homogeneous molecular M/NHC catalysis). In such systems,
taining the high efficiency of well-dened M/NHC systems in
when strong bases like alkali metal alkoxides or hydroxides are
the catalysis of numerous reactions mediated by strong oxygen
applied, O–NHC coupling can represent a serious problem that
bases.
needs to be solved for providing stability and high performance
On the other hand, the base-mediated O–NHC coupling can
of the catalytic systems.
serve as a driving force in the activation of M/NHC systems for
On the other hand, the opposite effect of the O–NHC
the reactions catalyzed by “NHC-free” metal species. The latter
coupling may be anticipated in reactions where M/NHC
scheme is valid, for example, for the high-temperature Mizor-
complexes serve as a source of “NHC-free” active metal
oki–Heck reaction.
species without typical metal–NHC bonds. As an example, the
Indeed, the correct choice of base is essential for maximizing
activity of Pd/NHC systems in the Mizoroki–Heck reaction is
the performance of the M/NHC catalytic systems and we antic-
determined predominantly by the cleavage of the metal–NHC
ipate many studies in this regard in the nearest future.
bond and generation of cocktail-type catalytic systems, in which
the “NHC-free” palladium species act as truly active catalytic
centers.18c The proposed pathways leading from M/NHC
complexes to the cocktails of active metal species include
transformation of the NHC ligands via C–H or C–C coupling and
Experimental section
General information
formation of corresponding azolium salts. The plausible role of 1H and 13C{1H} NMR spectra were acquired on a Bruker DRX
aliphatic amine bases as hydride sources and reductants of 500 instrument at 500 MHz and 125 MHz, respectively, in
metal cations in M/NHC complexes to produce azolium salts DMSO-d6 or CDCl3. H and 13C{1H} chemical shis are given
1
and “NHC-free” active metal species via H–NHC (C–H) coupling in ppm relative to the residual peak of the solvent (d 2.5 for
was reported recently.11 As described here, a principally new DMSO and 7.26 for CHCl3) for the proton spectra and the 13C
mechanism for generation of the “NHC-free” active species can {1H} DMSO-d6 signal (d 39.5) or the CDCl3 signal (d 77.2) for the
be implemented in the presence of oxygen bases like KOH, t- carbon spectra.
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High-resolution mass spectra were obtained on a Bruker
1-Methylbenzimidazole,22 1,3-dimethyl-1H-benzimidazol-3-
maXis Q-TOF or microTOF instruments (Bruker Daltonik GmbH, ium iodide (1a),23 1,3-diethyl-1H-benzimidazol-3-ium bromide
Bremen, Germany) equipped with an electrospray ionization (ESI) (1b),24 1,3-di-n-propyl-1H-benzimidazol-3-ium iodide (1c),11 1,3-
ion source. The experiments were performed in positive (+) MS di(propan-2-yl)-1H-benzimidazol-3-ium bromide (1d),25 1,3-
ion mode (HV Capillary: 4500 V; Spray Shield Offset: ꢂ500 V) with dibutyl-1H-benzimidazol-3-ium bromide (1f),14 1-butyl-3-
a scan range of m/z 50–1500. External calibration of the mass methyl-1H-benzimidazol-3-ium iodide (1g),14 1,3-dibenzyl-1H-
spectrometer was achieved using a low-concentration tuning mix benzimidazol-3-ium
chloride
(1h),18c
1,3-dibenzyl-1H-
solution (Agilent Technologies). Unless otherwise stated, direct benzimidazol-3-ium bromide (1i),18c 1,3-bis[2,6-di(propan-2-yl)
syringe injection was applied for the analyzed solutions in MeCN phenyl]-1H-imidazol-3-ium chloride (1j),14 1,3-bis(2,4,6-trime-
(ow rate: 3 mL ꢃ minꢂ1). Nitrogen was applied as the nebulizer thylphenyl)-1H-imidazol-3-ium chloride (1k),14 1,3-dimethyl-1H-
gas (0.4 bar) and dry gas (4.0 L ꢃ minꢂ1, 180 ꢀC). All the MS imidazol-3-ium iodide (1l),14 1,4-dimethyl-4H-1,2,4-triazol-1-
spectra were recorded with 1 Hz frequency and processed using ium iodide (1n),14 1,4-dibenzyl-4H-1,2,4-triazol-1-ium chloride
Bruker Data Analysis 4.0 soware.
(1o),18c 4-benzyl-1-tert-butyl-4H-1,2,4-triazol-1-ium bromide
HPLC analyses were accomplished using an Agilent 1260 (1p),14
(1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-ylidene)
Innity LC system equipped with a reversed-phase Zorbax SB- diiodo(pyridine)palladium (2a),18c (1,3-dipropyl-1,3-dihydro-
C18 column (50 ꢃ 4.6 mm) thermostated at 35 C and a detec- 2H-benzimidazol-2-ylidene)(diiodo)(pyridine)palladium (2c),11
ꢀ
tion wavelength of 280 nm. Gradient elution with a 1 mL minꢂ1 dibromo[1,3-di(propan-2-yl)-1,3-dihydro-2H-benzimidazol-2-
ow rate was applied. The mobile phase A consisted of 10% ylidene](pyridine)palladium (2d),26 dibromo(1,3-dibutyl-1,3-
MeCN aqueous solution, the phase B was neat MeCN, and the dihydro-2H-benzimidazol-2-ylidene)(pyridine)palladium (2f),18c
phase C was 0.02 M NaClO4 aqueous solution. The following dichloro(1,3-dibenzyl-1,3-dihydro-2H-benzimidazol-2-ylidene)-
gradient conditions were used: ramp over 3 min from 80% A (pyridine)palladium (2h),18c dibromo(1,3-dibenzyl-1,3-dihydro-
and 20% C to 80% B and 20% C; then hold 5 min.
2H-benzimidazol-2-ylidene)(pyridine)palladium (2i),18c {1,3-bis
GC-MS experiments were carried out with an Agilent 7890A GC [2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H-imidazol-2-ylidene}
system, equipped with an Agilent 5975C mass-selective detector dichloro(pyridine)palladium (2j),27 {1,3-bis[2,6-di(propan-2-yl)
(electron impact, 70 eV) and a HP-5MS column (30 m ꢃ 0.25 mm phenyl]-1,3-dihydro-2H-imidazol-2-ylidene}(dichloro)(3-chloro-
ꢃ 0.25 mm lm) using He as carrier gas at a ow of 1.0 mL minꢂ1
.
pyridine)palladium (2k),28 [1,3-bis(2,4,6-trimethylphenyl)-1,3-
For electron microscopy measurements, the samples were dihydro-2H-imidazol-2-ylidene](dichloro)(pyridine)palladium
mounted on a 25 mm aluminum specimen stub, xed by (2l),28 [1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-
conductive carbon tape and coated with a thin lm (15 nm) of ylidene](dichloro)(3-chloropyridine)palladium (2m),28 (1,3-
carbon. The observations were carried out using a Hitachi dimethyl-1,3-dihydro-2H-imidazol-2-ylidene)diiodo(pyridine)
SU8000 eld-emission scanning electron microscope (FE-SEM). palladium (2n),18c dichloro(1-butyl-3-methyl-1,3-dihydro-2H-
Images were acquired in secondary electron mode at 10 kV imidazol-2-ylidene)(pyridine)palladium (2o),18c (2,4-dimethyl-
accelerating voltage and at a working distance of 4–5 mm. The 2,4-dihydro-3H-1,2,4-triazol-3-ylidene)diiodo(pyridine)palladium
morphology of the samples was studied taking into account the (2p),18c dichloro(2,4-dibenzyl-2,4-dihydro-3H-1,2,4-triazol-3-ylidene)-
possible inuence of the carbon coating on the surface. EDS- (pyridine)palladium (2q),18c (4-benzyl-2-tert-butyl-2,4-dihydro-3H-
SEM studies were carried out using an Oxford Instruments X- 1,2,4-triazol-3-ylidene)dibromo(pyridine)palladium (2r),18c di-m-bro-
max 80 EDS system at 10 kV accelerating voltage and at mo(dibromo)bis[1,3-di(propan-2-yl)-1,3-dihydro-2H-benzimidazol-
a working distance of 15 mm.
2-ylidene]dipalladium (3),25 bis(1,3-dimethyl-1,3-dihydro-2H-
Raman spectra were recorded using an InVia Raman benzimidazol-2-ylidene)diiodopalladium (4a),29 bis(1,3-dipropyl-
microscope (Renishaw, UK) equipped with a 20 mW 514.5 nm 1,3-dihydro-2H-benzimidazol-2-ylidene)(di-iodo)palladium (4b),11
argon laser. All the spectra were collected using a 50ꢃ objective (1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-ylidene)diiodo-
lens, 20 s of acquisition time, and 3 accumulations. A silicon (pyridine)platinum (5a),30 dibromo[1,3-di(propan-2-yl)-1,3-
wafer was used for calibration.21
C, H, and N elemental analyses were performed using a Per- bis(1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-ylidene)diiodo-
kinElmer 2400 elemental analyzer. Melting points were deter- nickel dibromo[bis(1,3-dibutyl-1,3-dihydro-2H-
(6a),32
dihydro-2H-benzimidazol-2-ylidene](pyridine)platinum (5b),31
mined in open capillary tubes using a Thiele apparatus and are benzimidazol-2-ylidene)]nickel (6b),14 1-butyl-3-methyl-1,3-
uncorrected. The Ni, Pd, and Pt contents in metal precipitates dihydro-2H-imidazol-2-one (7l),33 and 2,4-dibenzyl-2,4-dihydro-
were determined by means of energy dispersive X-ray uores- 3H-1,2,4-triazol-3-one (7n)34 were synthesized as described in
cence spectroscopy (ARL Quant0X EDXRF Analyzer, Thermo the literature. All other chemicals were commercially available.
Scientic). For the analyses, the weighed samples of metal
precipitates were dissolved in aqueous aqua regia.
1-Methyl-3-(propan-2-yl)-1H-benzimidazol-3-ium iodide (1e)
Experiments concerning reactions of M/NHC complexes with
bases were performed under an argon atmosphere using stan- A mixture of 1-methylbenzimidazole (1.3 g, 0.01 mol), isopropyl
˚
dard Schlenk techniques. Solvents were dried over activated 3 A iodide (3.4 g, 0.02 mol) and acetonitrile (15 mL) was heated
molecular sieves and degassed by argon bubbling within under reux for 24 h. Then the reaction mixture was evaporated
20 min. Preparative column chromatography was performed to dryness in vacuo. The residue obtained was recrystallized
using silica gel 60 (230–400 mesh, Merck).
from the MeCN–acetone 1 : 2 mixture, washed with acetone and
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dried in vacuo. Yield 2.69 g (89%) of colorless crystals, mp 195– neutralized with HCl solution to pH 8–9 under an argon
198 ꢀC. 1H NMR (DMSO-d6): d 1.62–1.63 (m, 6H, 2CH3), 4.09 (s, atmosphere. The resulted mixture was centrifuged and analyzed
3H, CH3), 5.04–5.12 (m, 1H, CH), 7.67–7.71 (m, 2H, Ar), 8.02– by HPLC and GC-MS. A precipitate separated by centrifugation
8.05 (m, 1H, Ar), 8.13–8.15 (m, 1H, Ar), 9.89 (s, 1H, H-2). 13C{1H} was washed sequentially with MeCN (3 ꢃ 4 mL), DMF (3 mL)
NMR (DMSO-d6): d 21.6, 33.4, 50.3, 113.5, 113.7, 126.26, 126.34, water (3 ꢃ 4 mL), and acetone (3 ꢃ 4 mL), and then dried in
130.2, 131.9, 141.1. ESI-MS(TOF) calcd for C11H15N2 [M ꢂ I]+ m/z vacuo to give corresponding metal powder, Pd(0) or Pt(0). The
175.1230, found m/z 175.1227.
organic solution formed aer centrifugation was combined
with washings and evaporated to dryness in vacuo. The residue
obtained was dissolved in CHCl3 (10 mL), washed with satu-
rated aqueous solution of NaCl (3 ꢃ 2 mL), dried with anhy-
drous Na2SO4 and evaporated to a small volume (ꢁ2 mL). The
corresponding azolones were isolated by ash chromatography
on silica gel. The yields of azolones are presented in Scheme 3,
Table S1.†
General procedure for the preparation of compounds 2b, e,
and g
A stirred mixture of corresponding azolium salts 1b, e, and g
(1.05 mmol), KBr or KI (5 mmol), anhydrous K2CO3 (690 mg, 5
mmol), PdCl2 (177 mg, 1 mmol) and dry pyridine (8 mL) was
ꢀ
heated for 16 h at 80 C in a sealed glass vial. Aer cooling to
Method B. A mixture of the complex 2–6 (0.3 mmol), 1,4-
dioxane (5 mL) and t-BuOK (336 mg, 3 mmol) was vigorously
stirred in a Teon screw cap tube at 100 ꢀC within 3–48 h (Table
S1†), then neutralized with HCl solution to pH ꢁ8 under an
argon atmosphere and treated as described in the method A.
The yields of azolones are presented in Scheme 3, Table S1.†
For the reactions of complexes 2–6 with bases under other
conditions, see Table S1 in the ESI.†
20 ꢀC, the reaction mixture was diluted with CH2Cl2 (20 mL) and
passed through a short pad of silica gel eluting with CH2Cl2
until the yellow product was completely recovered. The ob-
tained solution was evaporated to dryness under vacuum (rotary
evaporator) at 40 ꢀC. The residue obtained was treated with
hexane (ꢁ10 mL). The precipitate formed was collected by
ltration and recrystallized from the CH2Cl2–hexan 1 : 3
mixture.
Dibromo(1,3-diethyl-1,3-dihydro-2H-benzimidazol-2-ylidene)-
(pyridine)palladium (2b). Yield 395 mg (76%), yellow prismatic
crystals. 1H NMR (CDCl3): d 1.72 (t, J ¼ 7.3 Hz, 6H, 2CH3), 4.93 (q,
J ¼ 7.3 Hz, 4H, 2CH2), 7.28–7.30 (m, 2H, Ar), 7.36–7.42 (m, 4H,
Ar), 7.77–7.80 (m, 1H, Ar), 9.10–9.11 (m, 2H, Ar). 13C{1H} NMR
(CDCl3): d 14.5, 44.0, 110.5, 123.1, 124.7, 134.4, 138.1, 152.8,
161.1. Anal. calcd for C16H19Br2N3Pd: C, 36.99; H, 3.69; N, 8.09.
Found: C, 37.15; H, 3.61; N, 7.89.
1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2-one (7a). Color-
1
ꢀ
less needles, mp 104–106 C (from heptane). H NMR (CDCl3):
d 3.42 (s, 6H, 2CH3), 6.95–6.98 (m, 2H, Ar), 7.08–7.11 (m, 2H, Ar).
13C{1H} NMR (CDCl3): d 27.3, 107.4, 121.3, 130.2, 154.8. ESI-
MS(TOF) calcd for C9H11N2O [M + H]+ m/z 163.0866, found m/z
163.0868. The physical and spectral characteristics of the product
obtained are identical to those described in the literature.16
1,3-Diethyl-1,3-dihydro-2H-benzimidazol-2-one (7b). White
solid, mp 53–57 ꢀC (from hexane). 1H NMR (CDCl3): d 1.34 (t, J ¼
7.2 Hz, 6H, 2CH3), 3.95 (q, J ¼ 7.2 Hz, 4H, 2CH2), 6.99–7.03 (m,
2H, Ar), 7.07–7.10 (m, 2H, Ar). 13C{1H} NMR (CDCl3): d 13.8,
36.0, 107.6, 121.0, 129.3, 153.8. ESI-MS(TOF) calcd for
Diiodo[1-methyl-3-(propan-2-yl)-1,3-dihydro-2H-benzimidazol-
2-ylidene](pyridine)palladium (2e). Yield 454 mg (74%), yellow
1
prismatic crystals. H NMR (CDCl3): d 1.78 (d, J ¼ 7.3 Hz, 6H,
2CH3), 4.17 (s, 3H, CH3), 6.00–6.08 (m, 1H, CH), 7.22–7.28 (m, 2H,
Ar), 7.34–7.37 (m, 3H, Ar), 7.55–7.56 (m, 1H, Ar), 7.75–7.78 (m, 1H,
Ar), 9.11–9.12 (m, 2H, Ar). 13C{1H} NMR (CDCl3): d 20.2, 35.7, 54.8,
110.3, 112.4, 122.6, 122.8, 124.7, 132.6, 136.6, 137.9, 154.1, 159.1.
Anal. calcd for C16H19I2N3Pd: C, 31.32; H, 3.12; N, 6.85. Found: C,
31.45; H, 3.19; N, 6.71.
C
11H15N2O [M + H]+ m/z 191.1179, found m/z 191.1176. The
physical and spectral characteristics of the product obtained are
identical to those described in the literature.35
1,3-Dipropyl-1,3-dihydro-2H-benzimidazol-2-one (7c). Color-
less oil. 1H NMR (CDCl3): d 0.97 (t, J ¼ 7.4 Hz, 6H, 2CH3), 1.74–
1.83 (m, 4H, 2CH2), 3.85 (t, J ¼ 7.3 Hz, 4H, 2NCH2), 6.96–7.02
(m, 2H, Ar), 7.04–7.10 (m, 2H, Ar). 13C{1H} NMR (CDCl3): d 11.5,
21.9, 42.8, 107.7, 120.9, 129.7, 154.5. ESI-MS(TOF) calcd for
(1-Butyl-3-methyl-1,3-dihydro-2H-benzimidazol-2-ylidene)-
(diiodo)(pyridine)palladium (2g). Yield 509 mg (81%), yellow
1
prismatic crystals. H NMR (CDCl3): d 1.09 (t, J ¼ 7.4 Hz, 3H,
C
13H19N2O [M + H]+ m/z 219.1492, found m/z 219.1488. The
CH3), 1.54–1.61 (m, 2H, CH2), 2.19–2.25 (m, 2H, CH2), 4.19 (s,
3H, CH3), 4.69–4.72 (m, 2H, NCH2), 7.25–7.28 (m, 2H, Ar),
7.34–7.37 (m, 4H, Ar), 7.74–7.77 (m, 1H, Ar), 9.07–9.08 (m, 2H,
Ar). 13C{1H} NMR (CDCl3): d 13.9, 20.5, 30.6, 36.1, 49.2, 110.0,
110.4, 122.89, 122.92, 124.7, 134.8, 135.5, 137.9, 154.0, 160.5.
Anal. calcd for C17H21I2N3Pd: C, 32.53; H, 3.37; N, 6.70.
Found: C, 32.38; H, 3.29; N, 6.83.
physical and spectral characteristics of the product obtained are
identical to those described in the literature.36
1,3-Di(propan-2-yl)-1,3-dihydro-2H-benzimidazol-2-one (7d).
Colorless prisms, mp 72–75 ꢀC (from hexane). 1H NMR (CDCl3):
d 1.53 (d, J ¼ 7.0 Hz, 12H, 4CH3), 4.75 (sept, J ¼ 7.1 Hz, 2H,
2CH), 7.03–7.06 (m, 2H, Ar), 7.14–7.16 (m, 2H, Ar). 13C{1H} NMR
(CDCl3): d 20.4, 45.0, 109.1, 120.4, 128.6, 153.2. ESI-MS(TOF)
calcd for C13H19N2O [M + H]+ m/z 219.1492, found m/z
219.1495. The physical and spectral characteristics of the
product obtained are identical to those described in the
General procedure for the reaction of complexes 2–6 with
KOH or t-BuOK
Method A. A mixture of the complex 2a, d, h, and i, and 4a literature.37
(0.3 mmol), pyridine (4 mL) and 3 M aqueous KOH solution (1
1-Methyl-3-(propan-2-yl)-1,3-dihydro-2H-benzimidazol-2-one
1
mL, 3 mmol) was vigorously stirred in a Teon screw cap tube at (7e). Yellowish crystals, mp 51–54 ꢀC (from hexane). H NMR
100 ꢀC within 3–24 h (Table S1†), then cooled to 20 ꢀC and (CDCl3): d 1.53 (d, J ¼ 7.0 Hz, 6H, 2CH3), 3.40 (s, 3H, CH3), 4.69–
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4.79 (m, 1H, CH), 6.96–7.00 (m, 1H, Ar), 7.04–7.11 (m, 2H, Ar), a 3.07 ꢃ 10ꢂ3 M solution (freeze–pump–thaw degassed) of the
7.11–7.15 (m, 1H, Ar). 13C{1H} NMR (CDCl3): d 20.4, 27.1, 45.1, corresponding Pd/NHC complexes 2a, b, o, and r, and 4a (100
107.5, 109.0, 120.8, 121.0, 128.3, 130.4, 154.0. ESI-MS(TOF) mL) in THF were charged into the tube under an argon back-
calcd for C11H15N2O [M + H]+ m/z 191.1179, found m/z ush, and the tube neck was closed with a septum. A red PEEK
191.1183. The physical and spectral characteristics of the capillary (72 cm) was pulled into the tube through the septum
product obtained are identical to those described in the and immersed into the reaction mixture. The tube was placed in
literature.38
a hot glycerol bath. Then, the tube was heated at 100 C under
ꢀ
1,3-Dibutyl-1,3-dihydro-2H-benzimidazol-2-one (7f). A yellowish continuous magnetic stirring. Aer heating for ꢁ1 min,
oil. 1H NMR (CDCl3): d 0.95 (t, J ¼ 7.4 Hz, 6H, 2CH3), 1.35–1.43 (m, a degassed 3.57 ꢃ 10ꢂ1 M solution of the corresponding base
4H, 2CH2), 1.71–1.75 (m, 4H, 2CH2), 3.88 (t, J ¼ 7.3 Hz, 4H, 2CH2), (100 mL) was injected into the ask via a syringe through the
6.98–7.01 (m, 2H, Ar), 7.05–7.09 (m, 2H, Ar). 13C{1H} NMR (CDCl3): septum. For KOH, solutions in H2O or H218O were used. For t-
d 13.9, 20.2, 30.6, 41.0, 107.7, 120.9, 129.7, 154.4. ESI-MS(TOF) BuOK, a THF suspension was applied. The reaction was moni-
calcd for C15H23N2O [M + H]+ m/z 247.1805, found m/z 247.1810. tored until the entire solution volume was transfused into the
The physical and spectral characteristics of the product obtained mass spectrometer. Azolones were monitored as signals of [M +
are identical to those described in the literature.35,39
K]+ ions.
MS/MS experiments. During the monitoring of the reaction
1-Butyl-3-methyl-1,3-dihydro-2H-benzimidazol-2-one
(7g).
1
Colorless oil. H NMR (CDCl3): d 0.95 (t, J ¼ 7.4 Hz, 3H, CH3), between 4a and KOH, a specied ion corresponding to the
1.37–1.42 (m, 2H, CH2), 1.71–1.74 (m, 2H, CH2), 3.42 (s, 3H, hydroxyl-complex 9 was studied according to the following
CH3), 3.88 (t, J ¼ 7.3 Hz, 2H, CH2), 6.95–7.01 (m, 2H, Ar), 7.07– procedure. Nitrogen was used as a collision gas. The isolated
7.10 (m, 2H, Ar). 13C{1H} NMR (CDCl3): d 13.9, 20.2, 27.2, 30.7, mass parameter corresponding to the center of the desired m/z
41.1, 107.5, 107.7, 121.1, 121.2, 129.6, 130.2, 154.6. ESI-MS(TOF) interval was set to the nearest tenth (m/z 471.0). The collision
calcd for C12H17N2O [M + H]+ m/z 205.1335, found m/z 205.1332. energy applied was 15 eV. In-Source Collision Induced Disso-
The physical and spectral characteristics of the product ob- ciation (ISCID) energy, which refers to the MS3 mode, was set to
tained are identical to those described in the literature.35
1,3-Dibenzyl-1,3-dihydro-2H-benzimidazol-2-one (7h). Color- sition factor was 2 to get a good-quality spectrum.
less prisms, mp 106–109 ꢀC (from hexane). 1H NMR (CDCl3): 1,3-Dimethyl-1,3-dihydro-2H-benzo[d]imidazol-2-one-18O (7a-
0 eV. To dene the number of time-of-ight events, the acqui-
d 5.13 (s, 4H, 2CH2), 6.87–6.89 (m, 2H, Ar), 6.96–6.99 (m, 2H, Ar), [18O]). A two-necked 30 mL glass ask equipped with a magnetic
7.27–7.29 (m, 2H, Ar), 7.31–7.36 (m, 8H, Ar). 13C{1H} NMR stirring bar was thoroughly ushed with argon streamed via
(CDCl3): d 45.2, 108.5, 121.5, 127.6, 127.8, 128.9, 129.5, 136.5, a syringe needle pinned into one ask neck through a rubber
154.7. ESI-MS(TOF) calcd for C21H19N2O [M + H]+ m/z 315.1492, cork. Then metallic potassium (117 mg, 3 mmol) and degassed
found m/z 315.1496. The physical and spectral characteristics of dry pyridine (1 mL) were charged into the ask via the second neck
the product obtained are identical to those described in the under an argon backush. Then the neck was closed with a septum
literature.40
pierced with a syringe needle attached to a calcium chloride tube
1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H-imidazol-2- for the gas outlet. The ask was placed into an ice-water bath. A
one (7i). White solid (from hexane). 1H NMR (CDCl3): d 1.24 (d, J degassed solution of H218O (100 mg, 5 mmol) in dry pyridine (1
¼ 6.9 Hz, 12H, 4CH3), 1.27 (d, J ¼ 7.0 Hz, 12H, 4CH3), 2.95–3.00 mL) was added dropwise via a syringe through the septum under
(m, 4H, 4CH), 6.40 (s, 2H, 2CH of imidazole), 7.26–7.28 (m, 4H, vigorous stirring and argon purging. Then a solution of H218O (0.9
Ar), 7.39–7.42 (m, 2H, Ar). 13C{1H} NMR (CDCl3): d 23.8, 24.0, mL) in pyridine (1 mL) was injected into the ask via a syringe
29.0, 113.3, 124.0, 129.6, 132.4, 147.5, 152.3. ESI-MS(TOF) calcd through the septum. Aer vigorous stirring for 10 min, the ask
for C27H37N2O [M + H]+ m/z 405.2900, found m/z 405.2899. The was purged with argon and a solution of the complex 2a (176 mg,
physical and spectral characteristics of the product obtained are 0.3 mmol) in pyridine (2 mL) was injected into the ask via
identical to those described in the literature.41
a syringe through the septum. Then the ask was placed in
1,3-Bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-one a thermostated oil bath and heated at 100 ꢀC with vigorous stirring
(7j). White solid, mp 186–188 ꢀC (from MeCN–water 1/2). 1H within 24 h, and then cooled to 20 C. The reaction mixture was
ꢀ
NMR (CDCl3): d 2.20 (s, 12H, 4CH3), 2.31 (s, 6H, 2CH3), 6.32 (s, neutralized with concentrated aqueous HCl to pH 6–7 under an
2H, 2CH of imidazole), 6.96 (s, 4H, Ar). 13C{1H} NMR (CDCl3): argon atmosphere and then centrifuged. The precipitate separated
d 18.1, 21.2, 112.4, 129.2, 132.4, 136.5, 138.5, 150.7. ESI-MS(TOF) was washed sequentially with MeCN (3 ꢃ 4 mL) and acetone (3 ꢃ 4
calcd for C21H25N2O [M + H]+ m/z 321.1961, found m/z 321.1963. mL). The centrifuged solution combined with washes was evapo-
The spectral characteristics of the product obtained are identical rated to dryness in vacuo. The residue obtained was extracted with
to those described in the literature.41
hot n-heptane (5 ꢃ 4 mL) at 90–100 ꢀC, and the extract was evap-
orated to dryness in vacuo (rotary evaporator) at room temperature.
The residue obtained was treated with hexane (ꢁ100 mL) at ꢂ15 ꢀC,
and the precipitate formed was collected by ltration and recrys-
Online ESI-MS monitoring of the O–NHC coupling reaction
Online monitoring of ions in the reaction progress was per- tallized from heptane to give 23 mg (47%) of compound 7a-[18O].
formed as follows.
Colorless needles, mp 106–108 ꢀC. 1H NMR (CDCl3): d 3.42 (s, 6H,
A 10 mL Schlenk tube equipped with a magnetic stir bar was 2CH3), 6.96–6.99 (m, 2H, Ar), 7.09–7.12 (m, 2H, Ar). 13C{1H} NMR
thoroughly ushed with Ar. Then degassed THF (4 mL) and
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(CDCl3): d 27.3, 107.4, 121.3, 130.1, 154.8. ESI-MS(TOF) calcd for 4H, Ar). ESI-MS(TOF) calcd for C12H21N2 [M ꢂ HCl ꢂ Cl]+ m/z
C9H11N218O [M + H]+ m/z 165.0908, found m/z 165.0906.
193.1699, found m/z 193.1690.
Reaction of complex 6a with KOH. A mixture of a solution of
A solution of 40 mg of the dihydrochloride (8b ꢃ 2HCl) in
compound 6a (181 mg, 0.3 mmol) in 1,4-dioxane (1.5 mL) and 0.5 mL of 10% aqueous KOH was extracted by C6D6 (1 mL). The
3 M aqueous KOH solution (1 mL, 3 mmol) was vigorously extract of N,N0-dipropylbenzene-1,2-diamine (8b, free base) was
stirred in a Teon screw cap tube at 100 ꢀC within 20 h, and then dried by Na2SO4 and then analyzed by NMR. H NMR (C6D6):
1
cooled to 20 ꢀC. The light blue-green precipitate of Ni(OH)2 was d 0.80 (t, J ¼ 7.4 Hz, 6H, 2CH3), 1.33–1.41 (m, 4H, 2CH2), 2.78–
separated by centrifugation, washed sequentially with hot 2.80 (m, 4H, 2CH2), 6.70–6.73 (m, 2H, Ar), 6.97–7.01 (m, 2H, Ar).
MeCN (3 ꢃ 5 mL), hot DMF (5 mL), water (3 ꢃ 5 mL), and again 13C{1H} NMR (C6D6): d 11.9, 23.1, 46.4, 112.4, 119.7, 138.1.
with MeCN (5 mL), then dried at 80 ꢀC in vacuo to constant weight
Reaction of compound 1f with t-BuOK. Based on the same
to give 25 mg (91%) of Ni(OH)2. Aer the separation of Ni(OH)2, procedure as indicated for the compound 1a above, compound
the reaction mixture was analyzed by HPLC and GC-MS to 1f (0.467 g, 1.5 mmol) afforded diamine 8c (ꢁ85% HPLC yield)
determine the yield of azolone 7a, then diluted with water (30 mL) and azolone 7f (ꢁ10% HPLC yield). The diamine 8c was isolated
and extracted with benzene (5 ꢃ 10 mL). The extract was evapo- as N,N0-dibutylbenzene-1,2-diamine diperchlorate (8c
ꢃ
rated to dryness in vacuo. The dark oily residue obtained was 2HClO4), yield 633 mg (67%), mp 135–138 ꢀC. 1H NMR (DMSO-
dissolved in 5 mL of 10% aqueous HCl solution, the solution was d6): d 0.91 (t, J ¼ 7.2 Hz, 6H, 2CH3), 1.34–1.41 (m, 4H, 2CH2),
treated with charcoal and evaporated in vacuo to dryness to give 1.58–1.61 (m, 4H, 2CH2), 3.14–3.17 (m, 4H, 2CH2), 7.00–7.05 (m,
whitish-pink crystals of N,N0-dimethylbenzene-1,2-diamine dihy- 4H, Ar). 13C{1H} NMR (DMSO-d6): d 13.6, 19.4, 28.9, 66.3, 118.6,
drochloride (8a ꢃ 2HCl). Yield 98 mg (78%), mp 167–170 ꢀC. 1H 123.4 (the signal of two aromatic carbons is broadened and
NMR (DMSO-d6): d 2.77 (s, 6H, 2CH3), 7.00–7.06 (m, 4H, Ar). 13
C
merged into the background). ESI-MS(TOF) calcd for C14H25N2
{1H} NMR (DMSO-d6): d 32.2, 118.1, 123.3 (the signal of two [M ꢂ HClO4 ꢂ ClO4]+ m/z 221.2012, found m/z 221.2008.
aromatic carbons is broadened and merged into the back-
ground). ESI-MS(TOF) calcd for C8H13N2 [M ꢂ HCl ꢂ Cl]+ m/z
Inuence of the O–NHC coupling reaction on the catalytic
activity of Pd–NHC complexes in the Mizoroki–Heck reaction
137.1073, found m/z 137.1073.
Reaction of compound 1a with t-BuOK. A mixture of
compound 1a (0.411 g, 1.5 mmol), 1,4-dioxane (25 mL) and t-
BuOK (1.68 g, 15 mmol) was vigorously stirred in a Teon screw
cap tube at 100 ꢀC within 20 h. According to the HPLC and GC-
MS analyses, the main reaction products were diamine 8a
(ꢁ82% HPLC yield) and 1,3-dimethyl-benzimidazol-2-one 7a
(ꢁ10% HPLC yield). The reaction mixture was neutralized with
10% HCl to pH ꢁ 10, diluted with water (80 mL) and extracted
with benzene (4 ꢃ 50 mL). The extract was dried with anhydrous
Na2SO4 and evaporated to dryness in vacuo. The dark oily
residue obtained was dissolved in 30 mL of hot 10% aqueous
HCl solution. The resulted solution was treated with charcoal
and evaporated to dryness in vacuo. The solid obtained was
recrystallized from MeCN to give whitish-pink crystals of N,N0-
dimethylbenzene-1,2-diamine dihydrochloride (8a ꢃ 2HCl),
yield 204 mg (65%). The physical and spectral characteristics of
the product obtained are identical to the product obtained from
the reaction of compound 6a with KOH.
Preparation of the catalyst (method A). Compound 2j (16 mg,
25 mmol) was dissolved in pyridine (1 mL) at 30 ꢀC within
15 min. Then, 0.1 mL (2.5 mmol of [Pd]) of the precatalyst
solution was added immediately as the catalyst to the reaction
mixture of the Mizoroki–Heck reaction.
Preparation of the catalyst (method B). A mixture of
compound 2j (16 mg, 25 mmol) and t-BuOK (28 mg, 0.25 mmol)
in pyridine (1 mL) was heated for 10 min at 100 ꢀC with vigorous
stirring (Scheme 9), then cooled to room temperature and
neutralized by the addition of pyridine hydrochloride (30 mg,
0.26 mmol). 0.1 mL (2.5 mmol of [Pd]) of the resultant mixture
was added as the catalyst to the reaction mixture of the Mizor-
oki–Heck reaction.
A 7 mL screw-capped glass tube equipped with a magnetic
stirring bar was charged with K2CO3 (138 mg, 1 mmol), PhI
(102 mg, 0.5 mmol), n-butyl acrylate (96 mg, 0.75 mmol) and
naphthalene (12.8 mg, 0.1 mmol) in DMF (0.9 mL). A solution of
the corresponding Pd catalyst (2.5 mmol, 0.5 mol%) in pyridine
(0.1 mL) prepared according to the method A or B was added to
the reaction tube. The tube was sealed with a screw cap, tted
with a septum and placed immediately in a thermostated oil
bath with vigorous stirring at 60 ꢀC, and that instant was taken
as the starting time of the reaction. Aer 20 hours, samples of
the reaction mixtures (1 mL) were taken up from the tubes,
diluted with MeCN (1 mL) and then subjected to analysis. The
yields (%) of coupling product 12 were determined by GC-MS
(naphthalene as internal standard).
A solution of 40 mg of 8a ꢃ 2HCl in 10% aqueous KOH (0.5
mL) was extracted by C6D6 (1 mL). The extract of N,N0-
dimethylbenzene-1,2-diamine (8a, free base) was dried by
1
Na2SO4 and then analyzed by NMR. H NMR (C6D6): d 2.41 (s,
6H, 2CH3), 6.62–6.65 (m, 2H, Ar), 6.98–7.01 (m, 2H, Ar). 13C{1H}
NMR (C6D6): d 30.7, 110.9, 119.6, 138.8. ESI-MS(TOF) calcd for
C8H13N2 [M + H]+ m/z 137.1073, found m/z 137.1074.
Reaction of compound 1c with t-BuOK. The reaction proce-
dure was analogous to the one for the compound 1a described
above. The compound 1c (0.495 g, 1.5 mmol) afforded diamine
8b (ꢁ83% HPLC yield) and azolone 7c (ꢁ8% HPLC yield). The
diamine 8b was isolated as N,N0-dipropylbenzene-1,2-diamine
dihydrochloride (8b ꢃ 2HCl), yield 179 mg (45%), mp 153–
Inuence of the O–NHC coupling reaction on the catalytic
activity of Pd–NHC complexes in the Suzuki–Miyaura reaction
1
156 ꢀC. H NMR (DMSO-d6): d 0.94 (t, J ¼ 7.4 Hz, 6H, 2CH3),
Preparation of the catalyst (method A). Compound 2j (4 mg,
1.65–1.70 (m, 4H, 2CH2), 3.06–3.09 (m, 4H, 2CH2), 6.98–7.05 (m, 6.25 mmol) was dissolved in DMF (0.1 mL) at 25 ꢀC within
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15 min. Then, 10 mL of the solution (0.625 mmol of [Pd]) was yields (%) of coupling product 16 were determined by GC-MS
mixed with 1,4-dioxane (0.1 mL), and a solution of pyridine (naphthalene as internal standard).
(0.5 mg, 6.3 mmol) in i-PrOH (0.1 mL). The resultant mixture was
added immediately as the catalyst to the reaction mixture.
Preparation of the catalyst (method B). Compound 2j (4 mg,
6.25 mmol) was dissolved in DMF (0.1 mL) at 25 ꢀC within 15 min.
Conflicts of interest
There are no conicts to declare.
Then, a mixture of 10 mL (0.625 mmol of [Pd]) of the precatalyst
solution, 1,4-dioxane (0.1 mL) and t-BuOK (0.7 mg, 6.25 mmol)
was heated for 10 min at 100 ꢀC with vigorous stirring, then Acknowledgements
cooled to room temperature and neutralized by addition of
The present study was supported by the Russian Science
Foundation RSF grant no. 14-23-00078 (mechanistic study and
investigation of the catalytic reactions) and by the Russian
a solution of pyridine hydrochloride (0.7 mg, 6.3 mmol) in i-PrOH
(0.1 mL). The resultant mixture was added as the catalyst to the
reaction mixture of the Suzuki–Miyaura Reaction.
Foundation for Basic Research, RFBR grants 16-29-10786
A 7 mL screw-capped glass tube equipped with a magnetic
(synthesis and transformations of metal complexes) and 17-33-
stirring bar was charged with a solution of 4-bromo-N,N-dime-
thylaniline (50 mg, 0.25 mmol), phenylboronic acid (43 mg, 0.35
50047 (ESI-MS studies of reaction intermediates). The authors
also thank the Shared Research Center “Nanotechnologies” of
mmol) and naphthalene (16 mg, 0.125 mmol), i-PrOH (0.5 mL),
the Platov South-Russian State Polytechnic University and the
and a solution of KOH (28 mg, 0.5 mmol) in H2O (0.4 mL). A
Department of Structural Studies of Zelinsky Institute of
solution of the Pd catalyst (0.625 mmol, 0.25 mol%) prepared
according to the method A or B was added to the reaction tube.
Organic Chemistry for analytical services. The authors are
grateful to Olga E. Eremina (Chemistry Department, Lomono-
The tube was purged with argon and sealed with a screw cap,
sov Moscow State University) for the Raman spectroscopy
tted with a septum and placed immediately in a thermostated
oil bath with vigorous stirring at 80 ꢀC, and that instant was
analysis.
taken as the starting time of the reaction. Aer 2 hours, samples
of the reaction mixtures (1 mL) were taken up from the tubes,
diluted with MeCN (1 mL) and then subjected to analysis. The
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