NHC stabilized Pd nanoclusters in the Mizoroki-Heck reaction within microemulsion: exploring the role of imidazolium salt in rate enhancement

Article abstract of DOI:10.1039/C8NJ05118F

We report the significant rate enhancement of the Mizoroki-Heck reaction by in situ generated palladium nanoclusters within the confined space of water-in-oil (w/o) mixed microemulsion (μE) formulated by sodium dodecylsulfate (SDS), polyoxyethylene (23) l

Full text of DOI:10.1039/C8NJ05118F

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NHC stabilized Pd nanoclusters in the Mizoroki–Heck
reaction within microemulsion: exploring the role
of imidazolium salt in rate enhancement†
b
Cite this:DOI: 10.1039/c8nj05118f
Koena Ghosh, *a Shubhajit Dhara,a Sourav Jana,a Subhomoy Das
Sudeshna Roya
and
We report the significant rate enhancement of the Mizoroki–Heck reaction by in situ generated palladium
nanoclusters within the confined space of water-in-oil (w/o) mixed microemulsion (mE) formulated by
sodium dodecylsulfate (SDS), polyoxyethylene (23) lauryl ether (Brij-35) and isopropyl myristate (IPM), in
the presence of novel imidazo[1,5-a]pyridinium chlorides as N-heterocyclic carbene (NHC) precursors.
This is the first endeavor to study an organic reaction in microemulsions containing IPM as
biocompatible green oil. A series of novel imidazo[1,5-a]pyridinium chlorides were synthesized in a cost
effective manner and were screened for typical Heck reaction between 4-iodotoluene and
a
a
nbutylacrylate. The optimum rate was achieved with 2-hydroxyphenylimidazo[1,5-a]pyridinium chloride at
low catalyst loading under mild conditions. Conductivity and FTIR measurements suggested an effective
change in the hydrogen bonding network of interfacial water in the presence of the NHC-precursor.
Strong evidence for in situ formation of the Pd–NHC complex was obtained which significantly accounts
for the rate enhancement. The reaction progresses rapidly with non-activated and sterically hindered aryl
halides under optimal conditions. We further report a unique isolation technique to separate IPM (oil)
from the reaction medium. The effect of NHC-precursors within the confined space of a microemulsion,
wherein the reaction takes place, is correlated with the observed rate enhancement.
Received 8th October 2018,
Accepted 20th December 2018
DOI: 10.1039/c8nj05118f
rsc.li/njc
preparation of pharmaceuticals3 and advanced materials.4
recent report shows an alternate cocktail-type catalysis in the
A
Introduction
Metal-catalyzed organic transformations have been recognized Pd–NHC catalyzed Mizoroki–Heck reaction where cleavage of a
as useful synthetic techniques to construct C–C bonds leading metal–NHC bond plays a crucial role in catalysis.5 Driven by the
to the formation of various complex molecular scaffolds having recent challenges in sustainable chemistry,6a,b development of novel
significant pharmaceutical and material properties. These reaction media containing water to achieve a higher rate, ambient
transformations rely on two crucial factors: a specific ligand reaction temperature, low catalyst consumption, easy product
for activating the metal center and the nature of the reaction separation and catalyst recovery is particularly advantageous.6
medium. Over the past few decades, remarkable progress in the However, the insolubility of organic compounds in water tends
design of N-heterocyclic carbene (NHC) based ligands has been to limit its applicability in a broad sense. A number of existing
accomplished by taking advantage of their strong s-donor unconventional solvents employing imidazole based ionic
capacity, thermal stability and low dissociation rates with liquids,7 ionic organic bases,8 inexpensive amphiphiles forming
tunable electronic and steric properties.1 The higher stability micelle or reverse micelle,7c,9–11 etc., are known to address
of metal–NHC (M–NHC) species enabling them to participate in insolubility issues associated with water.11 These entities are able
reactions under diverse conditions adds to their potentiality for to co-solubilize inorganic salts, as well as otherwise insoluble
widespread application in homogeneous catalysis,2 e.g. cross- organic compounds in water.
coupling reactions, C–H activation, metathesis, etc., for the
Notably, water-in-oil (w/o) microemulsion systems are homo-
geneous mixtures of oil, water, surfactant and/or co-surfactant,
which contain individual domains of oil and water separated by
a monolayer of surfactant and/or co-surfactant at the micro-
scopic level. The highly dynamic charged interfacial region of
these microstructures allows easy accumulation of reacting
a Department of Chemistry, Presidency University, 86/1 College Street,
Kolkata 700 073, India. E-mail: koena.chem@presiuniv.ac.in;
Fax: +91-33-2241-3893; Tel: +91-33-2241-3893
b Department of Chemistry, Indian Institute of Technology Kanpur,
Kanpur-208016, India
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c8nj05118f species at the monolayer where water soluble components get
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encapsulated into the water domain.12 Such droplet based nano- hydrocarbon tails of the two surfactants.18a The choice of IPM
sized micro-fluids serve as nano-reactors which break down was made considering its biocompatible nature and extensive
and recombine within nanosecond time scale and allow very use in drug delivery systems.18b,c In addition, 1-pentanol was
fast material exchange. This facilitates a reaction resulting in used as the co-surfactant (Pn) for stabilization of the system
optimum reagent consumption and rapid mixing of substrates due to its biological and technological implications.19 Notably,
in terms of improved reaction rates.11,13 Water in nanodroplets mixed surfactants play a prominent role in surface chemical
exhibits properties different from bulk due to imposed geometric applications because they are cost effective and often exhibit
constraints from the restrictive H-bonding network. This unique pronounced interfacial properties. The interactions between
physicochemical behaviour of microemulsions gives rise to the constituent surfactants can lead to either synergism (attractive)
exceptional chemical reactivity when used as a solvent.11 More- or antagonism (repulsive) based on their physicochemical
over, such systems have already been recognized as economically properties. At the equimolar composition of ionic–nonionic
viable templates for the preparation of nanoparticles in a simple mixed surfactant, superior activity is commonly achieved com-
manner.7,14 A crucial balance between stability and flexibility of the pared to the individual components.20
microemulsion is essential to achieve optimum rate enhancement
Synthesis of imidazo[1,5-a] pyridinium ions from
pyridine-2-carboxaldehyde
which relies on the system composition, temperature, and nature
of the additive used.15
The present study usefully combines the advantages of a w/o
microemulsion system as reaction medium with heightened
reactivity of in situ generated NHC–Pd catalyst in the Mizoroki–
Heck coupling reaction at ambient condition as a benchmark
for evaluation. We have prepared novel NHC-precursors for this
purpose. This extremely useful catalytic reaction often requires
temperature higher than or in the vicinity of 100 1C, even in
water or in a microemulsion.7c,16,17 We are able to conduct
successful coupling reactions in isopropyl myristate (IPM) blended
biocompatible microemulsion, typically around 45 1C via an
operationally simple protocol. We report herein the experimental
results of the remarkable rate enhancement of the Mizoroki–Heck
reaction under optimized conditions. Our systematic investigation
illustrates how perturbation induced by the NHC-precursor
encapsulated confined space of an organized assembly affects
the rate of the reaction within ‘nano-reactor’, by conductivity
and vibrational spectroscopic measurement via D2O probing.
Recently, imidazolium-based surface-active ionic liquids were
reported to promote the Suzuki reaction in microemulsion at
room temperature using conventional organic solvent.7b In
contrast, we have carefully chosen IPM based biocompatible
mE as a green reaction medium. We have developed a unique
isolation technique to separate IPM (oil) from the reaction
medium. The recyclability of the catalytic system is also discussed.
To the best of our knowledge, such a comprehensive study on
IPM-derived w/o mixed surfactant microemulsion as a biocom-
patible template for catalytic organic transformation has not
been reported in the literature so far.
A few novel imidazo[1,5-a]pyridinium chlorides with varying
degrees of steric and electronic properties were prepared from
commercially available pyridine-2-aldehyde, aryl amines and
formaldehyde in the presence of a catalytic amount of HCl
following a single step protocol (Scheme 1).21 The pure salts
were obtained in 76–87% yields after crystallization from
acetonitrile/THF or ethanol/diethyl ether. Characterization of
all the new compounds was done by spectroscopic studies.22
Encapsulation of the NHC-precursor in the chosen
microemulsion droplet
The imidazolium salts (L1–L5) were encapsulated in chosen
anionic, non-ionic and mixed w/o microemulsion templates
(0.02 mmol in B2 mL) at o 20, in which NHC-precursors
containing aqueous nanodroplets were suspended in the bulk
oil phase stabilized via the surfactant monolayer.22,23 The NHC-
precursors in such a system are likely to orient at the oil–water
interface in such a way that the polar part of the molecule
enters the water domain and the non-polar part extends into
the hydrocarbon tail of the surfactant molecules (or surfactant
palisade layer). The formation of optically isotropic, transparent
and stable homogeneous dispersions of NHC encapsulated w/o
microemulsion was also evident from visual observation (Fig. 1).
Results and discussion
We prepared three types of water-in-oil (w/o) microemulsion
systems with single anionic (sodium dodecylsulfate, SDS), non-
ionic (polyoxyethylene (23) lauryl ether, Brij-35) and equimolar
mixture of anionic–nonionic (SDS/Brij-35) surfactants using
isopropyl myristate (IPM) as the bulk oil phase. Surfactants
(SDS and Brij-35) having same hydrocarbon chain length (con-
stituting 12 carbon atoms in the linear chain of the tail) were
typically chosen to minimize possible interactions between the
Scheme 1 Preparation of imidazo[1,5-a]pyridinium chloride, L1–L5.
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(2.0 mL). All three types of microemulsion (anionic, nonionic and
mixed) systems were screened to obtain the most suitable reaction
medium. The Heck reaction was performed with in situ generated
2 mol% Pd–NHC (1 : 2) complex. The reaction progressed
smoothly to completion within 45 min. at 50 1C, resulting in
the desired cross-coupled product ((E)-nbutyl-3-(p-tolyl)acrylate)
5a along with the homo-coupled product (Table 1, entries 1–3).
In anionic (SDS), mixed (SDS and Brij-35) and non-ionic (Brij-35)
microemulsion systems, 46%, 55% and 40% of the desired Heck
coupled product (entries 1–3) were obtained, respectively. The
reaction was also performed in the absence of an additive or in
water or IPM as solvent to validate the superior activity of the
NHC-precursor in the confined environment (entries 4–8). All
these results are summarized in Fig. 2 (bar diagram) and Table 1.
The formation of cross-coupled product was confirmed by
spectral analysis.22 Further optimization with water soluble
bases, e.g. potassium carbonate and tetramethyl ethylenediamine
(TMEDA), produced almost comparable yields of the desired
product, 43% and 46%, respectively (entries 9 and 10), whereas
for triethylamine (TEA), 55% of the Heck product was obtained
(entry 2). It is noteworthy that stoichiometric amount of base was
essential for the reaction, to neutralize the acid produced (herein,
HI) in the reaction medium. Moreover, the higher yield of the
Heck reaction in mixed microemulsion systems suggests pre-
dominant ion–dipole interactions between mixed surfactant
polar head group and TEA within a confined environment.
Fig. 1 Representative photographs of water-in-oil (w/o) single and mixed
microemulsion (SDS/Brij-35/Pn/IPM, o = 20) in the absence and presence
of an active NHC-precursor. (A) Mixed mE, (B) mixed mE containing L1,
(C) mixed mE containing L5, (D) single mE containing L2, (E) mixed mE
containing L2, (F) single mE containing L3, (G) mixed mE containing L3.
Enhanced activity of the NHC-precursor in the confined
environment of w/o microemulsion
We chose 4-iodotoluene (1.0 equiv.) and n-butyl acrylate
(1.2 equiv.) as coupling partners of our model system in the
presence of triethylamine (2.0 equiv.) to investigate the catalytic
performance of imidazo[1,5-a]pyridinium salt L1 as a ligand in the
palladium catalysed Mizoroki–Heck reaction in w/o microemulsion
Table 1 Screening of reaction conditions for the C–C cross-coupling Heck reactiona
Entry
Solvent
NHC-precursor (L)
Base
5b (%)
1
2
3
4
5
6
7
8
Anionic surfactant (SDS) blended (w/o) mE
Mixed surfactant (SDS/Brij-35) blended (w/o) mE
Non-ionic surfactant (Brij-35) blended (w/o) mE
Waterc
L1
L1
L1
—
—
—
—
—
L1
L1
L2
L2
L2
L3
L3
L3
L4
L4
L4
L5
L5
L5
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
K2CO3
TMEDA
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
46
55
40
Trace (7)d
8 (11)d
30 (35)d
38 (41)d
31 (35)d
43
Isopropyl myristate (IPM)c
Anionic surfactant (SDS) blended (w/o) mE
Mixed surfactant (SDS/Brij-35) blended (w/o) mE
Non-ionic surfactant (Brij-35) blended (w/o) mE
Mixed surfactant (SDS/Brij-35) blended (w/o) mE
Mixed surfactant (SDS/Brij-35) blended (w/o) mE
Anionic surfactant (SDS) blended (w/o) mE
Mixed surfactant (SDS/Brij-35) blended (w/o) mE
Non-ionic surfactant (Brij-35) blended (w/o) mE
Anionic surfactant (SDS) blended (w/o) mE
Mixed surfactant (SDS/Brij-35) blended (w/o) mE
Non-ionic surfactant (Brij-35) blended (w/o) mE
Anionic surfactant (SDS) blended (w/o) mE
Mixed surfactant (SDS/Brij-35) blended (w/o) mE
Non-ionic surfactant (Brij-35) blended (w/o) mE
Anionic surfactant (SDS) blended (w/o) mE
Mixed surfactant (SDS/Brij-35) blended (w/o) mE
Non-ionic surfactant (Brij-35) blended (w/o) mE
9
10
11
12
13
14
15
16
17
18
19
20
21
22
46
65
82 (88)d
49
50
62
44
52
66
45
56
73
47
a
Unless otherwise mentioned, reactions were performed at 50 1C for 45 min using aryl halides (0.5 mmol), nbutyl acrylate (0.6 mmol), base
b
c
(1 mmol), Pd(OAc)2 (2 mol%), L (4 mol%), in 2 mL of microemulsion containing 0.5 mmol of surfactant with o = 20. Isolated yields. Reaction
was performed in 2 mL of corresponding pure solvent. HPLC yield.
d
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Table 2 Optimization of the Heck reactiona
L2
Yieldc
Entry Solventb
Catalyst (x mol%) (y mol%) (%)
1.
2.
3.
4.
5.
6.
7.
8.
w/o mixed mE, o = 20
Pd(OAc)2 (2 mol%)
Pd(OAc)2 (2 mol%)
Pd(OAc)2 (2 mol%)
Pd(OAc)2 (2 mol%)
Pd(OAc)2 (4 mol%)
Pd(OAc)2 (1 mol%)
PdCl2 (2 mol%)
Pd(OAc)2 (2 mol%)
Pd(OAc)2 (2 mol%)
Pd(OAc)2 (2 mol%)
4
4
4
4
4
4
4
2
6
4
4
88d
71
61
48
89
69
76
71
60
85
62
w/o mixed mE, o = 30
w/o mixed mE, o = 40
w/o mixed mE, o = 50
w/o mixed mE, o = 20
w/o mixed mE, o = 20
w/o mixed mE, o = 20
w/o mixed mE, o = 20
w/o mixed mE, o = 20
DMF, 90 1C
Fig. 2 The Mizoroki–Heck reaction between 4-iodotoluene and nbutyl
acrylate in the presence of imidazolium salts (L1–L5) as additive.
9.
10.e
11.e
DMF : H2O (9 : 1), 90 1C Pd(OAc)2 (2 mol%)
This increases the availability of TEA in the vicinity of the
interfacial region and in confined water. Consequently, the
formation of OHÀ base surrounding the interface is expected to
proceed in the following way:24
a
Reactions were performed at 50 1C for 45 minutes using 4-iodotoluene
(0.5 mmol), nbutyl acrylate (0.6 mmol), triethylamine (1 mmol), in 2 mL
of solvent. Reactions were performed in mixed surfactant (SDS/Brij-35)
b
blended (w/o) microemulsion as solvent unless otherwise mentioned.
c
d
e
Isolated yields. HPLC yield. Reaction was continued overnight.
(C2H5)3N + H2OR(C2H5)3NÁH2OR(C2H5)3NH+ + OHÀ.
(1)
interactions between the surfactant head group and TEA which
resulted from a decrease in surfactant concentration on the
droplet surface. These results suggest that the reaction took
place neither in the water nor in the oil domain exclusively;
rather, it occurred in the palisade layer of the oil–water inter-
face of the microemulsion. The inference is well corroborated
by previous reports where the most plausible reaction location
was identified to be either interfacial region or within the
surfactant palisade layer of the w/o microemulsion.12,14a,25
The methodology was further optimized by altering the
metal salt (Pd(II) acetate, Pd(II) chloride, etc.), mol% ligand,
etc. The experimental findings are summarized in Table 2. A
nearly equal yield of the Heck product was obtained by loading
2 or 4 mol% Pd(II) acetate (Table 2, entries 1 and 5). However,
considering the development of greener protocol, further studies
are conducted with 2 mol% in situ generated Pd–NHC complex
Here, penetration of OHÀ in the palisade layer of w/o microemulsion
cannot be ruled out, and subsequently, a basic environment in the
vicinity of the interface appears to be advantageous for the catalytic
efficiency. The inherent problem of using IPM based biocompatible
microemulsion as organic reaction media is associated with the high
boiling nature of IPM which makes the isolation procedure a little
cumbersome and tends to limit its application. We have developed a
novel separation method where IPM is converted to myristic
acid with the application of dilute acid under mild conditions
and precipitated out from the reaction medium. Thereafter, a
regular workup followed by a purification allows easy recovery of
the desired product.22
Evaluation of reactivity of NHC-carbene precursors (L2–L5) in
w/o microemulsion for the Mizoroki–Heck reaction
Encouraged by the findings, catalytic efficiency of a series of (1 : 2) using L2 in mixed mE system. Any deviation from these
NHC-precursors (L2–L5) was screened in our model system for optimized condition produced a lower yield of the Heck product
the Pd-catalyzed Heck reaction at o 20 following the procedure (Table 2, entries 8 and 9) which demonstrated a crucial role of
discussed in the previous section. In all these cases, the reaction the ligand and system composition in the Heck reaction.
proceeded smoothly to completion and all the data are pre- Nevertheless, the reaction proceeded in common organic solvents
sented in Table 1 (entries 11–22). Interestingly, the highest yield viz. DMF and DMF–water mixture yielding 85% and 62% desired
of the Heck product was obtained in the mixed microemulsion product, respectively, only after overnight heating at 90 1C (entries
system using L2 (yield 88%, Table 1, entry 12). With other 10 and 11). These results signify the improved performance of
precursors L3, L4 and L5, 62%, 66% and 73% yields were the Mizoroki–Heck reaction in the microemulsion in contrast
obtained, respectively (entries 15, 18 and 21). Further, dependence to commonly used organic solvents.
of the catalytic activity on the micro-heterogeneity of the micro-
In order to investigate the substrate scope of the methodology,
emulsion was studied by varying various components like a number of aryl halides, e.g. activated and non-activated aryl
water content (o), additive and palladium concentration. Upon iodides, bromides and chlorides, were treated with nbutyl acrylate
increasing water content of the microemulsion (o from 20 to 50), under optimized condition. The reaction proceeded efficiently with
the yield of the desired product dropped from 88% to 48% a range of electron deficient and electron rich aryl iodides, and non-
(Table 2, entries 1–4) probably due to a decrease in ion–dipole activated aryl bromides (Table 3, entries 1–7). With activated and
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Table 3 Mizoroki–Heck reaction with aryl halides and nbutylacrylate in
ligand (L2) encapsulated w/o mixed microemulsiona
Scheme 2 The Mizoroki–Heck reaction of aryl halides with styrene within
Pd–NHC encapsulated w/o mixed microemulsion.
Entry
1
Aryl halide (4)
5, yieldb
Enhanced flexibility of the NHC-precursor encapsulated
droplet nanoreactor
To further examine any correlation between the observed rate
enhancement in the Heck reaction and the active NHC-precursor
L2 (as ligand), conductivity measurements were carried out in
mixed mE system (water/SDS/Brij-35/Pn/IPM). The change in
conductivity of the system was measured by varying the water
content (o) of the medium in the presence of the active NHC-
precursor (L2) at 50 1C. The conductance data are plotted as a
function of o (Fig. 3). Initially, conductivity increased gradually
up to o B30; thereafter, a steeper increase in the overall
conductivity of the system was observed (L2, Fig. 3). Control
experiments without NHC-precursors were also performed for
comparison. The critical value for a sharp linear increase in
conductivity is known as percolation threshold point.26 As per
the general idea, if droplets are non-interacting hard sphere
type, no significant increase in conductance occurs, whereas,
with an increase in fluidity of the droplet interface, a sharp rise
in conductance is expected as a result of faster coalescence
of water droplets. This fission and fusion process permits
fast material exchange which essentially promotes the rates of
organic reactions.13b,27
2
3
4
5
6
7
5a, 74%
5a, 17%
The influence of the ligand structure (L2) was monitored by
control experiments where conductivity of the system was
measured (i) without ligand and (ii) with ligand L3 in which
free OH functionality of imidazopyridine salt L2 is substituted
with (–OMe) group (Scheme 1). The conductivity vs. o plot
8
a
Reactions were performed at 50 1C for 45 minutes using aryl halide
(1.0 equiv.), nbutyl acrylate (1.2 equiv.), triethylamine (2 equiv.), Pd(OAc)2
(2 mol%), L2 (4 mol%) in mixed surfactant (SDS/Brij-35) blended (w/o)
b
microemulsion as solvent at o 20. Isolated yields of the products.
c
HPLC yield.
non-activated aryl chlorides, the Heck product yield was only 17%
and 33%, respectively (Table 3, entries 7 and 8).
To broaden the substrate scope further, the coupling
partner was changed from acrylate to styrene (Scheme 2). To
our delight, the cross-coupling reaction proceeded smoothly to
afford asymmetrical stilbene derivative (6) with both electron
rich aryl iodide and bromide in high yields (79% and 75%,
respectively).
Fig. 3 Electrical conductivity of SDS/Brij-35 blended w/o mixed surfactant
microemulsion in the absence and presence of an active NHC-precursor.
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(curves a–c, Fig. 3) displayed similar patterns in all the three molecules occupy the cores of the water pool of w/o microemulsion
cases. The maximum increase in the conductivity was noted and possess a strong hydrogen bonding network among them-
for mE system containing L2 with a simultaneous increase in selves, i.e. their properties are similar to bulk water. Such a
percolation threshold point in comparison to ligand free or L3 H-bond shifts the O–D stretching band towards lower frequency
encapsulated mE system. A significant increase in percolation in region around 2450 cmÀ1. The bound water, viz. the surfactant
L2 containing mE indicates a better attractive interaction among head group-bound water molecules, appear around 2550 cmÀ1
.
the droplets which possibly allows material exchange at a faster The water molecules dispersing within long hydrocarbon chains
rate.28 This phenomenon advocates for a higher efficiency of the surfactant are termed ‘trapped water’ which is matrix-
of the Mizoroki–Heck reaction within the nano-reactor. The isolated dimeric or monomeric in nature and absorbs around
relatively low yields of the Heck product in precursor free or L3 2650 cmÀ1
containing mE systems also corroborates the above fact (Table 1,
.
A comparison between the individual curves 1–3 of Fig. 4A
entry 15). It can be noted that free OH functionality of L2 can vs. B demonstrates that the presence of the NHC-precursor L2
make hydrogen bond with surfactant charged head group in water pool of microemulsion causes substantial perturbation
present at the interface, changing the interfacial architecture of water microstructures in which the abundance of free water
of nano-reactor within the confinement. Similar studies correlating was decreased (curve 1), the population of bound water was
`
the effect of additives on changing interfacial flexibility vis-a-vis increased (curve 2) and the population of trapped water exhibited a
percolation threshold of microemulsion systems by conductivity marginal variation (curve 3). The bound water molecules generally
experiments have previously been reported.25a
reside at the interfacial region. The increase in bound water
content in the presence of L2 suggested that L2 essentially resided
at the interface. This allowed a change in the hydrogen bonding
network dynamics of water within the nano-confinement which
was correlated with the rate enhancement of the Heck reaction.
Extended H-bonding network in the presence of the NHC-
precursor in the confinement
Possible alteration of water microstructure within the confine-
ment was monitored employing FTIR measurement via D2O
probing. The study was conducted with the imidazolium salt
(L2) encapsulated mixed microemulsion system at a fixed water
content (o = 20) at 30 1C. The sample was prepared using 10%
D2O containing water which forms HOD through rapid
exchange between H and D atoms.18b Use of HOD as a probe
is particularly advantageous as the O–D band can be decoupled
from the O–H band appearing in a region of 2200 cmÀ1 to
2700 cmÀ1. This region corresponds to the fingerprint region of
the vibrational stretch of O–D bonds in water29 which remain
comparatively separated from other strong absorption bands of
the constituents of the microemulsion and/or the additive.19b
Earlier reports showed water molecules exist in three ‘states’ or
‘layers’ in w/o microemulsion which are detectable through
FTIR measurements.30 The corresponding O–D bands are fitted
as the sum of Gaussian bands using Gaussian curve fitting
program following a three-state model which confirms the
existence of water molecules in three different modes inside
the nano-pool, namely (i) free water, (ii) bound water and
(iii) trapped water. The deconvoluted FTIR spectra (experimental)
are depicted in Fig. 4A and B. According to this model, free water
Role of palladium
In situ formation of Pd–NHC complex is strongly suggested
from the 13C NMR spectrum of freshly prepared Pd–NHC in
encapsulated microemulsion system, accorded in D2O. The
characteristic C2 signal of free NHC species L2 was found to
shift from 149.6 ppm to 175 ppm (Fig. 5). A downfield shift of
the same carbon (B20 ppm) for Pd–NHC complex is consistent
with the data reported earlier.7a,b,31 In the 13C NMR spectrum
recorded after the product recovery, from the aqueous layer
containing Pd–NP, the Pd–NHC peak at 175 ppm still persisted,
albeit in a low intensity. We believe that the probable accumu-
lation of the NHC-precursor L2 containing OH functionality
at the interface influences the availability of in situ generated
Pd–NHC in the vicinity of the reaction site, which facilitated the
Mizoroki–Heck reaction.
In the HRTEM measurement after the nanoparticle formation,
we observed Pd–NP of average size 5.53 + 0.63 nm forming an
assembly of nanoparticles with an average size of B25 nm
(Fig. 6).7c,32 It is likely that the Pd–NPs owe their stability during
repetitive catalytic cycles to such a cluster formation. The catalyst
was recycled up to four times. After the second cycle 77% of the
product was isolated. Similarly, the third and fourth cycles
afforded the desired product in 69% and 58% yields, respectively.
A significant decrease in the yield of the Mizoroki–Heck reaction
Fig. 4 FTIR study of SDS/Brij-35 blended w/o mixed surfactant microemulsion
(A) in the absence and (B) in the presence of an active NHC-precursor
(10% D2O).
Fig. 5 13C NMR spectrum showing the formation of a Pd–NHC species.
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IPM which was sonicated to result in fresh microemulsion
formulation. Fresh starting materials, IPM (oil), Pn (co-surfactant)
and nonionic surfactant (Brij-35) were added (as these components
could be removed at the time of product extraction) to the remnant
aqueous part which contained the catalytic system and anionic
surfactant (SDS) from the first run.
Conclusion
Fig. 6 High resolution transmission electron microscopy (HRTEM) analysis of
isolated Pd nano-cluster in w/o mixed microemulsion (SDS/Brij-35/Pn/IPM) in
the presence of additive L2 (at two different magnifications).
We have successfully developed an operationally simple protocol
for the Mizoroki–Heck reaction with high yields under relatively
mild conditions. Novel (1,5-a)-imidazo-pyridinium chlorides were
synthesized as NHC-precursors in w/o microemulsion (water/
SDS/Brij-35/Pn/IPM) as an unconventional solvent system. NMR
evidence for the formation of Pd–NHC molecular complex sug-
gests catalysis by a Pd–NHC complex in the confinement of an
organized nanoreactor accompanied by an enhanced rate of
reaction. It is possible that the phenolic –OH group of the ligand
L2 allows its accumulation at the aqueous interface localizing the
catalyst concentration. The formation of microassembly of
nanoparticles (Pd nanocluster) is indicative of the reservoir of
Pd during catalysis. The applications of the present w/o micro-
emulsion system in similar organic transformations, and their
further mechanistic elucidation are currently under study in our
laboratory.
was observed after the fourth cycle, possibly because of the
agglomeration of Pd(0) particles.
Experimental procedure
General procedure of the Heck reaction
Into a 10 mL glass reaction vial fitted with screw cap, 2 mL
microemulsion (water/SDS/Brij-35/Pn/IPM) of fixed o (= [water]/
[surfactant]), 4 mol% active NHC-precursor (L) (0.02 mmol) and
2 mol% Pd(OAc)2 (0.01 mmol) were added. The mixture was
placed in a preheated oil bath at 30 1C with constant sonication
till all the solid material dissolved. Into this mixture were
added 4-iodotoluene (0.5 mmol), n-butyl acrylate (0.6 mmol)
and triethylamine (1.0 mmol), and the mixture was heated at
50 1C for 45 min. The progress of the reaction was monitored by
thin layer chromatography (TLC) on silica gel.
Conflicts of interest
There are no conflicts to declare.
Workup procedure to break IPM based biocompatible
microemulsion
Acknowledgements
K. G. thanks SERB, DST, India (grant number SB/FT/CS-032/
2012), CSIR, India (grant number 02(0326)/17/EMR-II) and
Presidency University (FRPDF grant) for financial support. We
thank Presidency University and IIT Kanpur for instrumental
supports. S. D. thanks SERB, DST, India, for research fellowship.
After the appropriate time, the reaction vessel was charged with
15 mg solid NaCl followed by 3 mL of 0.6 N HCl. The mixture
was stirred for 30 min till an off-white precipitate of myristic
acid appeared. An additional 10 min stirring was continued for
the complete precipitation of insoluble materials. The mixture
was filtered and the filtrate was extracted with ethyl acetate
(3 Â 10 mL). The collected organic layer was washed with brine,
dried over anhydrous sodium sulphate and the solvent was
removed under reduced pressure. The residue was purified by
column chromatography on silica gel using a mixture of ethyl
acetate and petroleum ether (1 : 99).
Notes and references
1 Some selected references: (a) A. J. Arduengo, Acc. Chem. Res.,
1999, 32, 913–921; (b) W. A. Herrmann, Angew. Chem., Int. Ed.,
2002, 41, 1290–1309; (c) F. E. Hahn and M. C. Jahnke, Angew.
Chem., Int. Ed., 2008, 47, 3122–3172; (d) S. D. Gonzalez,
N. Marion and S. P. Nolan, Chem. Rev., 2009, 109, 3612–3676;
(e) H. Jacobsen, A. Correa, A. Poater, C. Costabile and
L. Cavallo, Coord. Chem. Rev., 2009, 253, 687–703; ( f ) D.-C.
The formation of the desired products was confirmed
1
through H NMR and 13C NMR.22 Similar concentration ratio of
reagents was maintained, in the case of experiments conducted in
other solvents.
¨
Thomas Droge and F. Glorius, Angew. Chem., Int. Ed., 2010, 49,
Procedure for recycling
6940–6952; (g) C. M. Latham, W. Lewis, A. J. Blake and
S. Woodward, Eur. J. Org. Chem., 2015, 1819–1823.
The reaction was performed in 2.5 mmol scale following the
above procedure. After the first run, excess IPM (B15 mL) was
added and the mixture was sonicated. A biphasic system was
formed from which the supernatant organic layer was taken out
with the help of a micropipette. Into the aqueous layer containing
Pd–NHC nanocluster were added necessary amounts of Brij-35,
2 Some selected references: (a) E. Peris and R. H. Crabtree, Coord.
Chem. Rev., 2004, 248, 2239; (b) N. Marion, O. Navarro, J. Mei,
E. D. Stevens, N. M. Scott and S. P. Nolan, J. Am. Chem. Soc.,
2006, 128, 4101–4111; (c) L. H. Gade and S. Bellemin-Laponnaz,
Coord. Chem. Rev., 2007, 251, 718; (d) E. A. B. Kantchev,
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2019
New J. Chem.

View Article Online
Paper
NJC
C. J. O. Brien and M. G. Organ, Angew. Chem., Int. Ed., 2007,
46, 2768–2813; (e) X.-F. Wu, P. Anbarasan, H. Neumann and
S. K. Saha and B. K. Paul, J. Surfactants Deterg., 2015, 18,
547–567.
¨
M. Beller, Angew. Chem., Int. Ed., 2010, 49, 9047–9050; 13 (a) M. Hager, F. Currie and K. Holmberg, Organic Reactions
( f ) G. C. Fortman and S. P. Nolan, Chem. Soc. Rev., 2011,
40, 5151–5169; (g) S. Wu¨rtz and F. Glorius, Acc. Chem. Res.,
2008, 41, 1523–1533; (h) C. Valente, S. Calimsiz, K. H. Hoi,
D. Mallik, M. Sayah and M. G. Organ, Angew. Chem., Int. Ed.,
2012, 51, 3314–3332; (i) H. Li, C. C. C. Johansson Seechurn
in Microemulsions, in Colloid Chemistry II. Topics in Current
Chemistry, ed. M. Antonietti, Springer, Berlin, Heidelberg,
2003, vol. 227, pp. 53–74; (b) M. A. Lpez-Quintelaa, C. Tojob,
´
M. C. Blancoa, L. GarcıaRioa and J. R. Leis, Curr. Opin.
Colloid Interface Sci., 2004, 9, 264–278.
and T. J. Colacot, ACS Catal., 2012, 2, 1147–1164; ( j) P. G. 14 (a) J. Eastoe, M. J. Hollamby and L. Hudson, Adv. Colloid
Gildner and T. J. Colacot, Organometallics, 2015, 34,
5497–5508.
Interface Sci., 2006, 5, 128–130; (b) A. K. Ganguli and
S. Vaidya, Chem. Soc. Rev., 2010, 39, 474–485.
3 (a) L. Oehninger, R. Rubbiani and I. Ott, Dalton Trans., 2013, 15 S. P. Moulik and B. K. Paul, Adv. Colloid Interface Sci., 1998,
42, 3269–3284; (b) F. Hackenberg, H. Mu¨ller-Bunz, R. Smith, 78, 99–195.
W. Streciwilk, X. Zhu and M. Tacke, Organometallics, 2013, 16 (a) J. G. de Vries, Dalton Trans., 2006, 421–429; (b) F. Christoffel
32, 5551–5560; (c) K. M. Hindi, M. J. Panzner, C. A. Tessier, and T. R. Ward, Catal. Lett., 2018, 148, 489–511.
C. L. Cannon and W. J. Youngs, Chem. Rev., 2009, 109, 17 (a) I. Volovych, Y. Kasaka, M. Schwarze, Z. Nairoukh,
¨
3859–3884; (d) F. Lazreg and C. S. J. Cazin, Medical Applications
of NHC-Gold and -Copper Complexes, in N-Heterocyclic
Carbenes: Effective Tools for Organometallic Synthesis, ed.
S. P. Nolan, Wiley-VCH Verlag GmbH & Co. KGaA, 2014,
ch. 7, pp. 173–198.
J. Blum, M. Fanun, D. Avnir and R. Schomacker, J. Mol.
Catal. A: Chem., 2014, 393, 210–221; (b) A.-E. Wang, J.-H. Xie,
L.-X. Wang and Q.-L. Zhou, Tetrahedron, 2005, 61, 259–266;
(c) S. Bhattacharya, A. Srivastava and S. Sengupta, Tetrahe-
dron Lett., 2005, 46, 3557–3560.
4 (a) C. I. Ezugwu, N. A. Kabir, M. Yusubov and F. Verpoort, 18 (a) S. Bardhan, K. Kundu, S. K. Saha and B. K. Paul, J. Colloid
Coord. Chem. Rev., 2016, 307, 188–210; (b) A. B. Miguel-
Interface Sci., 2013, 411, 152–161; (b) Colloids in Biotechnol-
ogy, ed. M. Fanun, CRC Press, USA, 2011; (c) S. Bardhan,
K. Kundu, G. Chakraborty, B. K. Paul, S. P. Moulik and
S. K. Saha, Bio-inspired microemulsions and their strategic
pharmacological perspectives, in Encyclopedia of Biocolloid
and Biointerface Science, ed. H. Ohshima, John Wiley & Sons,
New Jersey, USA, 2016, ch. 10, pp. 122–144.
´
Coello, M. Bardajı, S. Coco, B. Donnio, B. Heinrich and
P. Espinet, Inorg. Chem., 2018, 57, 4359–4369; (c) X. Zhang,
B. Cao, E. J. Valente and T. K. Hollis, Organometallics, 2013,
32, 752–761.
5 A. V. Astakhov, O. V. Khazipov, A. Y. Chernenko, D. V.
Pasyukov, A. S. Kashin, E. G. Gordeev, V. N. Khrustalev,
V. M. Chernyshev and V. P. Ananikov, Organometallics, 2017, 19 (a) F. Lopez, G. Cinelli, L. Ambrosone, G. Colafemmina,
36, 1981–1992.
A. Ceglie and G. Palazzo, Colloids Surf., A, 2004, 49, 237–243;
(b) M. L. Curri, A. Agostino, L. Manna, M. D. Monica, M. Catalano,
L. Chiavarone, V. Spagnolo and M. Lugara, J. Phys. Chem. B, 2000,
104, 8391–8397.
6 (a) S. Chandrasekhar, C. Narsihmulu, S. S. Sultana and
N. R. Reddy, Org. Lett., 2002, 4, 4399–4401; (b) T. Dwars,
E. Paetzold and G. Oehme, Angew. Chem., Int. Ed., 2005, 44,
7174–7199; (c) L. Yu, Y. Huang, Z. Wei, Y. Ding, C. Su and 20 (a) Mixed Surfactant Systems, ed. J. F. Scamehorn, K. Ogino
Q. Xu, J. Org. Chem., 2015, 80, 8677–8683; (d) T. Kitanosono,
K. Masuda, P. Xu and S. Kobayashi, Chem. Rev., 2018, 118,
679–746; (e) J. Chen, J. Wu and T. Tu, ACS Sustainable Chem.
Eng., 2017, 5, 11744–11751.
7 (a) G. Zhang, H. Zhou, J. Hu, M. Liu and Y. Kuang, Green
Chem., 2009, 11, 1428–1432; (b) M. Hejazifar, M. Earle,
K. R. Seddon, S. Weber, R. Zirbs and K. Bica, J. Org. Chem.,
and M. Abe, Dekker, New York, 1993; (b) S. Bardhan,
K. Kundu, S. Das, M. Poddar, S. K. Saha and B. K. Paul,
J. Colloid Interface Sci., 2014, 430, 129–139; (c) S. Bardhan,
K. Kundu, B. Kar, G. Chakraborty, D. Ghosh, D. Sarkar,
S. Das, S. Senapati, S. K. Saha and B. K. Paul, RSC Adv., 2016,
6, 55104–55116; (d) E. Odella, R. D. Falcone, J. J. Silber and
N. M. Correa, J. Phys. Chem. B, 2018, 122, 4366–4375.
2016, 81, 12332–12339; (c) M. Taskin, A. Cognigni, R. Zirbs, 21 J. T. Hutt and Z. D. Aron, Org. Lett., 2011, 13, 5256–5259.
E. Reimhult and K. Bica, RSC Adv., 2017, 7, 41144–41151; 22 See ESI†.
(d) P. Migowski and J. Dupont, Chem. – Eur. J., 2007, 13, 23 o denote mole ratio of water vs. surfactant.
32–39; (e) J. Dupont, Acc. Chem. Res., 2011, 44, 1223–1231.
8 H.-J. Xu, Y.-Q. Zhao and X.-F. Zhou, J. Org. Chem., 2011, 76,
8036–8041.
9 B. H. Lipshutz and B. R. Taft, Org. Lett., 2008, 10, 1329–1332.
10 (a) V. Calo, A. Nacci, L. Lopez and N. Mannarini, Tetrahe-
dron Lett., 2000, 41, 8973–8976; (b) J.-Z. Jiang and C. Cai,
J. Colloid Interface Sci., 2006, 299, 938–943.
24 N. Li, Q. Cao, Y. Gao, J. Zhang, L. Zheng, X. Bai, B. Dong, Z. Li,
M. Zhao and L. Yu, Chem. Phys. Chem., 2007, 8, 2211–2217.
25 (a) A. Cid, J. F. Galvez, E. Barreiro and J. C. Mejuto, Tenside,
Surfactants, Deterg., 2018, 55, 110–115; (b) S. K. Mehta,
K. Kaur, E. Arora and K. K. Bhasin, J. Phys. Chem. B, 2009,
113, 10686–10692; (c) M. Hager, U. Olsson and K. Holmberg,
Langmuir, 2004, 20, 6107–6115; (d) K. Holmberg, Curr. Opin.
¨
11 K. Holmberg, Eur. J. Org. Chem., 2007, 731–742 & references
therein.
12 (a) I. Danielsson and B. Lindman, Colloids Surf., 1981,
3, 391–392; (b) S. Bardhan, K. Kundu, G. Chakraborty,
Colloid Interface Sci., 2003, 8, 187–196; (e) J. Sjoblom,
R. Lindberg and S. E. Friberg, Adv. Colloid Interface Sci.,
1996, 65, 125–287; ( f ) M.-J. Schwuger, K. Stickdorn and
R. Schomaecker, Chem. Rev., 1995, 95, 849–864.
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2019

View Article Online
NJC
Paper
26 X. Zhang, Y. Chen, J. Liu, C. Zhao and H. Zhang, J. Phys. 30 (a) T. K. Jain, M. Varshney and A. Maitra, J. Phys. Chem.,
Chem. B, 2012, 116, 3723–3734.
27 A. Jada, J. Lang and R. Zana, J. Phys. Chem., 1989, 93,
1989, 93, 7409; (b) Y. Gao, N. Li, L. Zheng, X. Bai, L. Yu,
X. Zhao, J. Zhang, M. Zhao and Z. Li, J. Phys. Chem. B, 2007,
111, 2506–2513.
10–12.
28 P. D. I. Fletcher, A. M. Howe and B. H. Robinson, J. Chem. 31 (a) H. Lebel, M. K. Janes, A. B. Charette and S. P. Nolan, J. Am.
Soc., Faraday Trans. 1, 1987, 83, 985–1006.
29 E. E. Fenn, D. B. Wong and M. D. Fayer, Proc. Natl. Acad. Sci.
U. S. A., 2009, 106, 15243–15248.
Chem. Soc., 2004, 126, 5046–5047; (b) C. Burstein, C. W. Lehmann
and F. Glorius, Tetrahedron, 2005, 61, 6207–6217.
32 An enlarged view of Fig. 6 (Fig S2) is included in ESI†.
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