Ferrocene-Labeled Carbon-Encapsulated Iron Nanoparticles: The First Magnetic Nanocatalysts for C-H Arylation toward 1,1′-Biphenyl Formation

Article abstract of DOI:10.1021/acs.oprd.8b00453

The first magnetic nanocatalysts for C-H arylation toward 1,1′-biphenyl formation are described. The nanocatalysts are based on conjugates of ferrocene and carbon-encapsulated iron nanoparticles. The highest catalytic activity was found for ferrocene conjugated to carbon-encapsulated iron nanoparticles via the N-methylpyrrolidine moiety. In the presence of the nanocatalyst, various 1,1′-biphenyls can be obtained in high yields (84-90%). The effect of substitution of the aniline's phenyl ring on the reaction yield is also included in this work. The nanocatalyst can be easily separated from the reaction mixture and can be reused in up to four reaction cycles without any loss of its high catalytic activity. Our work sheds light on a potential application of functionalized carbon-encapsulated iron nanoparticles in modern industrial organic processes toward more economical manufacturing of organic compounds.

Full text of DOI:10.1021/acs.oprd.8b00453

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Communication
Ferrocene-Labelled Carbon-Encapsulated Iron Nanoparticles: The First
Magnetic Nanocatalysts for C-H Arylation Toward 1,1’-Biphenyl Formation
Artur Kasprzak, Michal Bystrzejewski, and Magdalena Poplawska
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.8b00453 • Publication Date (Web): 21 Feb 2019
Downloaded from http://pubs.acs.org on February 22, 2019
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Ferrocene-Labelled Carbon-Encapsulated Iron
Nanoparticles: The First Magnetic Nanocatalysts
for C-H Arylation Toward 1,1’-Biphenyl
Formation
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Artur Kasprzak,a* Michał Bystrzejewski,b and Magdalena Poplawskaa
a
Faculty of Chemistry, Warsaw University of Technology, Noakowskiego Str. 3, 00-664
Warsaw, Poland
b Faculty of Chemistry, University of Warsaw, Pasteura Str. 1, 02-093 Warsaw, Poland
*corresponding author e-mail: akasprzak@ch.pw.edu.pl
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TABLE OF CONTENTS GRAPHIC:
NH2
6
7
1)
, NaNO2, HCl
G
G
8
9
2) 5 mol% Fc (nanocatalyst)
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e
F
nanocatalyst =
Fe
conjugates of ferrocene
and carbon-encapsulated iron nanoparticles
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ABSTRACT:
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The first magnetic nanocatalysts for C-H arylation toward 1,1’-biphenyl formation are
described. The nanocatalysts are based on the conjugates of ferrocene and carbon-
encapsulated iron nanoparticles. The highest catalytic activity was found for ferrocene
conjugated to carbon-encapsulated iron nanoparticles via the N-methylpyrrolidine moiety. In
the presence of the nanocatalyst, various 1,1’-biphenyls can be obtained with high yields (84-
90%). The effect of substitution of the aniline’s phenyl ring on the reaction yield is also
included in this work. The nanocatalyst can be easily separated from the reaction mixture and
can be reused up to four reaction cycles without any loss of its high catalytic activity. Our
work sheds a light on potential application of functionalized carbon-encapsulated iron
nanoparticles in modern, industrial organic processes towards more economical
manufacturing of organic compounds.
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KEYWORDS: C-H arylation, carbon-encapsulated iron nanoparticles, magnetic nanocatalyst,
ferrocene, graphene-related material
INTRODUCTION:
The undoubted importance of 1,1’-biphenyls synthesis results from their various
applications, for example in medicinal chemistry1 and other applied sciences.2 A number
methods for 1,1’-biaryl formation have been reported, mainly metal-catalyzed homogeneous
processes, such as Suziki-Miyaura coupling3 (Pd-catalyzed), Kumada coupling4 (Pd- or Ni-
catalyzed), Negishi coupling5 (Pd- or Ni-catalyzed) or Ullmann reaction6 (Cu-catalyzed).
These methods have been reported to produce the desired 1,1’-biaryls with high yields.
Commonly, in these processes the specific and harmful reactants need to be used, such as pre-
synthesized organozinc- or Griniard-type reagents, that require special handling under inert
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conditions. Importantly, such synthetic methodologies require the use of metal-based coupling
partners or metal-bearing homogeneous catalysts. This is an issue from the practical point of
view, mainly because of difficult catalyst separation and recycling.7 The industrial production
of 1,1’-biaryls may require the use of significant amounts of highly toxic metal-containing
compounds, what raises the key-issues associated with enlarging the reaction scale. This
feature is also unfavorable in the field of medicinal chemistry. From the point of drug
synthesis there is an urgent need to avoid the time-consuming removal of the metal artifacts
from the obtained 1,1’-biaryl.8 These drawbacks have stimulated the exploration of new ways
of the 1,1’-biaryl synthesis, also including the methods using metal-free catalysts.9–11 The
immobilization of a metal-based catalyst on solid supports (including zeolites and carbon
materials) is one of the most emerging concepts that enable the facile separation and recycling
of the catalyst.12–15 However, from the practical and industrial point of view, the common
drawbacks of such concepts are (i) the complexity of the solid support preparation, as well as
(ii) the requirement of applying harsh reaction conditions because of the limited contact time
between the reagents and the heterogeneous catalyst.
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The application of ferrocene (Fc) derivatives in catalysis is intensively studied.16,17
Because of the reversible red-ox reactions of this organometallic compound, Fc may act as a
catalyst in reaction paths based on various single-electron transfer oxidation or reduction
processes.18–21 One of the most emerging areas of catalytic applications of Fc-based
compounds is the carbon-carbon bond formation toward the synthesis of biaryl motifs, termed
as C-H arylation or arene C-H insertion. Several methodologies employing the Fc-based
palladium complexes as the catalysts were developed.22–24,10,11 In these processes a cross-
coupling partner and a specific aryl derivative together with a catalysts of relatively
sophisticated structure, is required. Very recently, native Fc25–28 or the conjugate of Fc and
graphene oxide29 were reported as the catalysts for the diverse C-H arylation reactions. These
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catalysts enabled the synthesis of various 1,1’-biphenyls in high yields, about 80 %. This
disclosure shows a potential of Fc in modern homogenous and heterogeneous catalysis.
Graphene-related nanostructures are the essential class of solid supports in
heterogeneous catalysis, owing to their high chemical inertness, high surface area and high
surface electron density resulting in a π-π staking phenomenon.30–32 Carbon-encapsulated iron
nanoparticles (CEINs) are the unique core-shell carbon nanomaterial. The iron core in CEINs
is covered by a carbon shell comprising the curved graphene layers.33–35 The mean diameter
of CEINs is 30-50 nm. The carbon shell in CEINs prevents the metallic core after oxidation
and limits spontaneous aggregation of nanoparticles. CEINs have similar surface properties
as, e.g., few-layer graphene. The presence of magnetic core makes this material mobile at an
external magnetic field and facilities its separation from solutions.33 Many diverse synthetic
methodologies for the surface functionalization of CEINs have been reported34,36–39, enabling
new and prospective applications of CEINs. Importantly, CEINs-based materials meet the
concept of magnetic nanocatalysis, which has been intensively explored research area in
recent years.40–44 The magnetic nanocatalysis enables to omit the drawbacks of homogenous
catalysis, such as time-consuming recovery and reuse of a catalyst and sophisticated
experimental procedures. The recent literature points many examples of catalytic applications
of carbon-encapsulated magnetic nanoparticles35,38,40,45,46, elucidating a great potential of
these materials in modern synthetic chemistry.
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Here we report the conjugates of Fc and CEINs as a new nanocatalyst for C-H
arylation reaction toward 1,1’-biphenyl formation. To the best of our knowledge, this study
reports for the first time the catalytically active magnetic materials for this process. The
synthesis of the nanocatalyst is simple, as well as the 1,1’-biphenyls can be produced in high
yields from the commercially-available reactants.
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EXPERIMENTAL DETAILS
Full experimental details are listed in the Experimental Section (see Section S1 in
Supplementary Information).
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General procedure for 1,1’-biphenyls formation using CEINs-Fc-1-CEINs-Fc-3 as the
nanocatalyst:
A flask equipped with a stirring bar was charged with aniline or given aniline derivative (0.8
mmol; 2 eq), HClaq (168 μL, 200.0 mg, 2 mmol; 12M HClaq added; 2.5 eq per 1 eq of aniline)
and acetone (1.5 mL). The content of the flask was cooled to 0°C using an ice bath. A
solution of NaNO2 (56.3 mg, 0.816 mmol; 1.02 eq per 1 eq of aniline) in a minimal amount of
distilled water was slowly added at 0-5°C. The mixture was stirred for 7.0 min at 0-5°C. The
as-obtained benzenediazonium salt was subjected to the reaction flask containing benzene
(35.7 μL, 31.3 mg, 0.4 mmol; 1 eq) and the given amount of nanocatalyst (CEINs-Fc-1 -
CEINs-Fc-3; 0.05 eq of ferrocene) in acetone (3 mL). The reaction mixture was sonicated at
25 °C for 5 hours. The nanocatalyst was then separated from the reaction mixture using a
neodymium magnet. The supernatant was separated from the nanocatalyst. The supernatant
was diluted with hexane (10 mL) and washed with saturated NaHCO3 (2 mL), water (3 mL)
and brine (2 mL). The organic layer was dried with anhydrous MgSO4 and concentrated under
reduced pressure. After purification of the product by means of PTLC, 1,1’-biphenyl or a
desired derivative of 1,1’-biphenyl was obtained (see data in Tables 1-4 for the reaction yields
and conditions).
RESULTS AND DISCUSSION
The synthesis of Fc-labelled CEINs was performed employing the protocols
previously reported by our group. The structures of the materials (CEINs-Fc-1-CEINs-Fc-3)
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are presented in Fig. 1. The materials were obtained (i) via the one-step cycloaddition reaction
(CEINs-Fc-147, CEINs-Fc-2)48, or (ii) employing the three-step protocol (CEINs-Fc-3)49.
Note that the materials differ in the type of linker between CEINs and Fc, as well as in content
of Fc moiety: 21.2 wt%, 16.3 wt% and 6.3 wt%, for CEINs-Fc-1, CEINs-Fc-2 and CEINs-
Fc-3, respectively. Importantly, the cyclic voltammetry studies revealed the electrochemical
activity of the nanoconjugates, because the fully reversible red-ox processes for Fc ligand
attached to CEINs was observed.47–49 Note that the microscopic studies (TEM) of various
functionalized CEINs (including CEINs-Fc-2) revealed that the core-shell morphology of the
obtained materials is retained after their surface modification, as well as no surface
degradation after the functionalization is observed.39,45,48,50
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N
N
O
O
H
e
F
e
F
N
N
e
F
H
Fe
Fe
Fe
CEINs-Fc-1
CEINs-Fc-2
CEINs-Fc-3
Fig. 1. Structures of studied conjugates.
The nanoconjugates were tested as nanocatalysts for C-H arylation in formation of
1,1’-biphenyl (Table 1). The reaction conditions were optimized using the CEINs-Fc-1
material as the nanocatalyst and benzene and aniline as the reactants. The experimental details
are given in the experimental section.51 In brief, the first step involved the treatment of aniline
(1) with sodium nitrite in the presence of hydrochloric acid. The as-obtained
benzenediazonium salt (2) was subjected to a reaction flask containing benzene and the
nanocatalyst in organic solvent.52 The obtained results are summarized in Table 1. The highest
reaction yield (90%) was observed for the reaction of 2 eq of aniline and 1 eq of benzene in
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the presence of 0.05 eq of Fc-labelled nanocatalyst in acetone (Table 1, entry 6).53 It is
noteworthy that no product was formed without a catalyst added (Table 1, entry 1). Secondly,
the usage of pristine CEINs as a nanocatalyst did not result in formation of the product (Table
1, entry 2). It means that the presence of Fc moiety on the surface of CEINs is essential for the
desired reaction path.
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Table 1. Optimization of the reaction conditions using CEINs-Fc-1 material as the
nanocatalyst.
N2+Cl-
NH2
NaNO2, HCl
0-5 °C
H2O/solvent
5 mol% Fc (CEINs-Fc-1)
25 °C
solvent
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2
3
Entry Benzene Aniline Fc (mass of the Solvent [first Reaction time Reaction
[eq]
[eq]
nanocatalyst)
[eq]([mg])a
step mL
second
mL]
+
[h]b
yield [%]c
step
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3
4
5
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9
1d
1 d
2
1
- (no catalyst added)
Acetone
(1.5+3)
9e
9e
9e
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0
1
- (30 mg of native Acetone
CEINs used) (1.5+3)
- (30 mg of native Acetone
0
1d
1
0
CEINs used)
0.05 (17.5)
(1.5+3)
Acetone
(1.5+3)
Acetone
(1.5+3)
Acetone
(1.5+3)
DMSO
(1.5+3)
Acetone
(1.5+3)
Acetone
(1.5+3)
1d
2
75
87
90
75
84
79
1d
2
0.10 (35.0)
0.05 (17.5)
0.05 (17.5)
0.05 (17.5)
0.05 (17.5)
5
1d
2
5
1d
1d
1d
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4
6
2
9
a calculations based on TGA data for Fc content in CEINs-Fc-1,
b reaction progress tracked with TLC,
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c isolated yields,
d 1 molar equivalent refers to 0.4 mmol of reactant,
e no conversion of reactants into desired product observed.
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The catalytic performance of CEINs-Fc-1 was compared with CEINs-Fc-2 and
CEINs-Fc-3 (Table 2). All the nanocatalysts had the catalytic activity in formation of 1,1’-
biphenyl. Noteworthy, CEINs-Fc-2 exhibited similar catalytic activity as CEINs-Fc-1 (Table
2, entries 2-3). This feature can be ascribed to the similar Fc content in these materials and to
the similar linkage between Fc ligand and the surface of CEINs. Interestingly, the catalytic
performance for CEINs-Fc-3 (Table 2, entries 4-5) was lower than for CEINs-Fc-1 and
CEINs-Fc-2. The first reason of this phenomenon might be associated with the lower content
of Fc ligand for CEINs-Fc-3 than for the other materials. Thus, higher mass of the catalyst
lowers dispersion stability of the material in organic solvent, because of the higher tendency
of the nanoparticles to aggregate. Note that the yield of the process did not change after
increasing twice the volume of the solvent for the reaction (Table 2, entry 5). The longer
aliphatic linker between Fc and CEINs might enable the attack of the as-generated aryl
radicals to the graphene-like surface of CEINs. Graphene-related surfaces are indeed known
to readily reacts with radicals.54–56 This hypothesis was evidenced via the analysis of FT-IR
spectra. The spectrum of CEINs-Fc-3 after the catalytic reaction clearly differs from the
spectrum of the material before the process.57 The new absorption bands located at 1595 and
695-620 cm-1 were indeed ascribed to the introduction of benzene-type moieties on the
surface of CEINs. Importantly, such difference in the FT-IR spectra of the nanocatalyst after
the reaction was observed neither for CEINs-Fc-1 nor for CEINs-Fc-2.58 This means that
these materials did no undergo any side-processes with the aryl radicals, most plausibly
because of higher ‘packing’ of the CEINs’ structure with Fc moieties for CEINs-Fc-1 and
CEINs-Fc-2 than for CEINs-Fc-3. The performed DLS measurements revealed that the
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CEINs-Fc-1 nanocatalyst exhibit the lowest mean hydrodynamic diameter (560 nm) among
all the studied materials (CEINs-Fc-2: 680 nm, CEINs-Fc-3: 880 nm) (size distribution
diagrams are presented in Section S5 in Supplementary Information). This feature can be
further ascribed to higher catalytic activity of CEINs-Fc-1 material in comparison to other
nanocatalysts, because of the higher surface area, easier accessibility of the Fc ligand and the
lower tendency of the nanocatalyst to aggregate.
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Table 2. Catalytic performance of CEINs-Fc-1, CEINs-Fc-2 and CEINs-Fc-3, together with
a reference test for pristine CEINs.
N2+Cl-
NH2
NaNO2, HCl
0-5 °C
H2O/acetone
5 mol% Fc (nanocatalyst)
25 °C
acetone
1
2
3
Entry Nanocatalyst
Fc (mass of the nanocatalyst) Reaction Reaction
[eq]([mg])a
time [h]b yield
[%]c
1
- (30 mg of pristine CEINs 9e
used)d
0
Fe
native CEINs
2
0.05 (17.5)d
5
90
N
e
F
Fe
CEINs-Fc-1
3
4
0.05 (22.7)d
5
4
86
62
N
O
e
F
Fe
CEINs-Fc-2
0.05 (58.7)d
O
H
N
N
e
F
H
Fe
CEINs-Fc-3
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0.05 (58.7)f
5
64
O
H
N
N
e
F
H
Fe
6
7
8
CEINs-Fc-3
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a calculations based on TGA data for Fc content in the given nanocatalyst,
b reaction progress tracked with TLC,
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c isolated yields,
d acetone (1.5+3 mL) used as solvent,
e no conversion of reactants into desired product observed,
f acetone (3+6 mL) used as solvent.
The results for the designed coupling reaction using CEINs-Fc-1 as the catalyst were
compared with the catalytic activity of previously reported homogenous and heterogeneous
catalysts for desired C-H arylation (Table 3). The direct comparison of these data brings a
conclusion that the herein developed nanocatalyst provides the highest reaction yield in the
shortest reaction time and under the mildest conditions. Note that this conclusion is also true
for the application of native Fc as the catalyst (Table 3, entry 2). Our method does not require
(i) the use of high molar equivalents of other additives (Table 3, entry 3) or (i) the use of high
mass of a catalyst (Table 3, entry 5). It is noteworthy that in a contrary to the method
employing the catalyst of relatively sophisticated structure (Table 3, entry 4), CEINs-Fc-1
preparation method is a simple one-step process, employing commercially available and low-
cost reactants. Thus, our synthetic methodology enables more economical manufacturing of
biphenyls. Additionally, the magnetic properties of the developed catalyst allow for its easy
separation from the reaction mixture (Fig. 2a). This feature makes our nanocatalyst easy to
recover and recycle, which are very important topics in terms of potential application of this
material in industrial processes.
After separation of CEINs-Fc-1 from the reaction mixture, the nanocatalyst was
washed with acetone, dried in oven at 50 °C for 1 day and reused. The recyclability studies
with CEINs-Fc-1 revealed that the developed nanocatalyst can be used up to four reaction
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cycles without any loss of its activity (Fig. 2b). For the fifth cycle a 6% decrease in the
reaction yield was observed.59 It is likely that this slight loss of activity after recycle #4 might
be associated with lowering of the dispersion stability of the nanocatalyst after the reaction
cycles.60 It should be highlighted that no changes in the FT-IR spectrum for CEINs-Fc-1
between the reaction cycles were observed.61
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Fig. 2. (a) Dispersion of CEINs-Fc-1 in acetone (2 mg/mL) (left) and magnetic response in
presence of neodymium magnet (right), (b) recyclability study of CEINs-Fc-1 (for the
reaction scheme, see Table 2)
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Table 3. Comparison of catalytic performance CEINs-Fc-1 with previously reported catalysts
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for 1,1-biphenyl (3) formation using aniline and benzene as the reactants.
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NH2
9
catalyst
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+
Entry Catalyst/additives
Molar
Reaction Reaction
Reaction Reference
equivalent time [h]
temperature yield
of
the
[°C]
[%]
catalyst
[eq]
1
0.05a
5
0-25
90
This work
N
e
F
Fe
CEINs-Fc-1
ferrocene
25
62
2
3
0.10
2.00
1.00
0.10
0.025
8
rt
84
55
p-toluenesulfonic acid
triethylorthoformate
copper (I) chloride
30
50
63
64
4
5
phenalenyl based-catalystb
12
15
rt
78
90
tetrakis(dimethylamino)ethylene 0.05
c
K-10 montmorillonite
-
110
a it refers to 17.5 mg of material,
b 9-methylamino-1-ethoxyphenalenium tetrafluoroborate,
c 2 g of the catalyst per 1 mmol of aniline.
In order to explore the effect of substitution on the yield of the designed catalytic
reaction, various anilines were used in the CEINs-Fc-1-catalyzed process (Table 4). The
anilines bearing the electron donating (i.e. CH3, OCH3, Br; Table 4, entries 1-4) or electron
withdrawing (i.e. NO2, Table 4 entries 5-6) substituents were tested. The reaction yields with
nitroanilines (93-90%) were slightly higher than for the native aniline (90%). The presence of
the electron donating group in the phenyl ring provided slightly lower reaction yields (88-
84%). Such a trend is in a good agreement with the data for the reactions catalyzed by the
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native Fc.25 The reaction yields for para-substituted anilines were slightly higher (1-2%) than
for the respective orto-derivatives, most plausibly due to the steric effect of the substituent.
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Table 4. The effect of aniline substitution on the yield of the developed CEINs-Fc-1-
catalyzed reaction.
N2+Cl-
NH2
G
NaNO2, HCl
G
G
0-5 °C
5 mol% Fc (CEINs-Fc-1)
H2O/acetone
25 °C
4 - 9
10 - 15
acetone
Entry Aniline derivativea
Product
Reaction yield [%]b,c
88
NH2
1
10
4
NH2
2
86
85
H3CO
11
OCH3
5
NH2
3
Br
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Br
6
NH2
Br
4
84
93
Br
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7
NH2
5
O2N
14
NO2
8
NH2
NO2
6
91
NO2
15
9
a for the native aniline (1,1’-biphenyl obtained) the yield of the reaction is 90%,
b isolated yields,
c reaction time: 5 h, 0.05 eq of the nanocatalyst.
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The proposed reaction mechanism is presented in Fig. 3.25,28 It involves a single
electron transfer that take place between the aryldiazonium salt and Fc-templated nanocatalyst
with subsequent formation of an aryl radical (Fig. 3a). In the second step, the aryl radical
intermediate with benzene is formed (Fig. 3b). Finally, a single-electron oxidation reaction
followed by acid-base reaction with Cl- (generated in the first step) restores the Fc catalyst
and provides the desired 1,1’-biphenyl (Fig. 3c). The first factor that influences on the high
catalytic activity of the studied materials is clearly ascribed to the presence of Fc moieties on
surface of CEINs. Adsorption of reactants on graphene-like surface of CEINs during the
chemical reaction30,65,66 is believed to be a synergistic interface effect that increases the
catalytic activity of the studied materials.
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+
N2 Cl-
N2 + Cl-
a)
b)
e
F
e
F
Fe
Fe
c)
Cl-
HCl
Fig. 3. Proposed reaction mechanism: (a) generation of aryl radical, (b) formation of aryl
radical intermediate with benzene, (c) formation of 1,1’-biphenyl.
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CONCLUSIONS
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7
8
In conclusion, we presented high catalytic activity of CEINs grafted with Fc in
formation of various 1,1’-biphenyls employing the C-H arylation process with commercially
available reactants. The highest catalytic activity was found for the nanoconjugate bearing the
N-methylpyrrolidine moiety. The synthesis path for this material is simple and is based on the
one-step reaction. The pure 1,1’-biphenyl was obtained in 90% yield under mild conditions at
short reaction time (5 h) using 0.05 molar equivalent of Fc-templated nanocatalyst. The
substitution of the aniline’s phenyl ring with electron-withdrawing groups provided higher
reactions (93-91%) in comparison to the electron-donating groups (88-84%). The catalyst can
be easily separated from the reaction mixture, as well as can be used up to four reaction cycles
without any loss of its activity. This work lays sheds a new light on the C-H arylation
reactions employing the magnetic nanocatalysts, towards their application in modern,
industrial organic processes.
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ASSOCIATED CONTENT
Supporting Information
Experimental
section,
NMR
and
FT-IR
data.
The Supporting Information is available free of charge on the ACS Publications website.
AUTHOR INFORMATION
Corresponding Author
akasprzak@ch.pw.edu.pl (Artur Kasprzak)
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AUTHOR CONTRIBUTIONS
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The manuscript was written through contributions of all authors. All authors have given
approval to the final version of the manuscript
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NOTES
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was financially supported partially by the National Science Centre (Poland), grant
No. 2016/21/N/ST5/00864, and Warsaw University of Technology. A. K. also acknowledges
the Foundation for Polish Science for the START scholarship and National Science Centre
(Poland), for the ETIUDA scholarship (No. 2018/28/T/ST5/00018).
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