Cellulose oxidation and the use of carboxyl cellulose metal complexes in heterogeneous catalytic systems to promote suzuki-miyaura coupling and C?O bond formation reaction

Article abstract of DOI:10.21577/0103-5053.20170051

This work shows the modification of microcrystalline cellulose by the selective oxidation of primary hydroxyl groups to carboxylate groups by a 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated system and its application as a heterogeneous ligand by ionic exchange with catalytic metals ions such as palladium, nickel and copper. Afterwards is described the application of the synthesized material as catalyst in coupling reactions such as Suzuki-Miyaura coupling and C?O bond formation reaction in different conditions, which are of great importance for the synthesis of drugs, natural products and new materials such as dendrimers, liquid crystals and polymers with magnetic and optical properties. The carboxyl cellulose matrix shows to have superior catalytic results as a ligand for all coupling reactions. Can be also highlighted the affinity of the carboxyl cellulose ligand in polar solvents such as water and alcohols and its application in mild conditions.

Full text of DOI:10.21577/0103-5053.20170051

http://dx.doi.org/10.21577/0103-5053.20170051
J. Braz. Chem. Soc., Vol. 28, No. 11, 2064-2072, 2017.
Printed in Brazil - ©2017 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Article
Cellulose Oxidation and the Use of Carboxyl Cellulose Metal Complexes in
Heterogeneous Catalytic Systems to Promote Suzuki-Miyaura Coupling and
C−O Bond Formation Reaction
Guilherme B. C. Martins,a Marcelo R. dos Santos,a Marcus V. R. Rodrigues,a
Renata R. Sucupira,a Luisa Meneghetti,a Adriano L. Monteirob and Paulo A. Z. Suarez*,a
aINCT-CATÁLISE, Laboratório de Materiais e Combustíveis, Instituto de Química,
Universidade de Brasília (IQ-UnB), Campus Universitário Darcy Ribeiro,
P.O. Box 4478, 70904-970 Brasília-DF, Brazil
bINCT-CATÁLISE, Laboratório de Catálise Molecular, Instituto de Química,
Universidade Federal do Rio Grande do Sul (IQ-UFRGS), 90040-060 Porto Alegre-RS, Brazil
This work shows the modification of microcrystalline cellulose by the selective oxidation of
primary hydroxyl groups to carboxylate groups by a 2,2,6,6-tetramethylpiperidine-1-oxyl radical
(TEMPO)-mediated system and its application as a heterogeneous ligand by ionic exchange with
catalytic metals ions such as palladium, nickel and copper.Afterwards is described the application
of the synthesized material as catalyst in coupling reactions such as Suzuki-Miyaura coupling
and C−O bond formation reaction in different conditions, which are of great importance for
the synthesis of drugs, natural products and new materials such as dendrimers, liquid crystals
and polymers with magnetic and optical properties. The carboxyl cellulose matrix shows to
have superior catalytic results as a ligand for all coupling reactions. Can be also highlighted
the affinity of the carboxyl cellulose ligand in polar solvents such as water and alcohols and its
application in mild conditions.
Keywords: cellulose modification, TEMPO oxidation, metal ligand, coupling reactions,
carboxyl cellulose
Introduction
cellulose may have a great potential of use in heterogeneous
catalysis.
Brazil is the fourth cellulose producer in the world and
in 2014 the production was 16.46 million tons (64% was
exported).1 However, most of the cellulose is used for paper
and other low cost products. Thus, it is important to develop
products by modifying cellulose in order to aggregate value
in such important feedstock. Indeed, some derivatives
have been developed and are actually manufactured on an
industrial scale and applied in coatings, laminates, optical
films, building materials, pharmaceuticals, foodstuffs and
cosmetics.2
On the other hand, the main challenge of modern
catalysis is to achieve environment-friendly processes,
using sustainable resources and very active catalysts.3-6 In
this regard, biopolymers are attractive for use combined
with transition metal catalysts for further applications in
organic synthesis, fine chemical and flow reactors,7-14 and
The formation of bonds catalyzed by transition metals is
considered one of the most important processes in synthetic
chemistry, helping to build complex molecules structures
from simple precursors.15 Cross-coupling reactions are
one of the most efficient methods for achieving this
goal, performing a reaction between an organometallic
compound and organic electrophile mediated by palladium,
nickel or copper complexes. Some important reactions in
this context, which are widely applied in organic synthesis,
can be mentioned, such as the Suzuki-Miyaura, Stille,
Negishi, Sonogashira, Mizoroki-Heck and Buchwald-
Hartwig couplings.16-18
Because of the characteristic insolubility of cellulose and
some of its derivatives, a plenty of studies has been carried
using those material as heterogeneous support in Suzuki-
Miyaura coupling reactions. Palladium nanoparticles have
been supported on cellulose without modification and
applied to Suzuki-Miyaura couplings.8 The modification
*e-mail: psuarez@unb.br

Vol. 28, No. 11, 2017
Martins et al.
2065
of cellulose to anchoring palladium species for catalytic
application in Suzuki-Miyaura reactions is also reported
in different ways, such as cellulose-aluminum oxide
composite modified with organic groups,9 modified
carboxymethyl cellulose19 and functionalized cellulose.20
In the last decade, the selective oxidation of the primary
alcohols of carbohydrates structure into carboxylates
using n-oxil-2,2,6,6-tetramethylpiperidine (TEMPO)
catalytic oxidation has been reported.21-24 This process has
also been applied to cellulose leading to new cellulose
derivative.25-27 The formation of carboxyl sites in cellulose
structure permits the directly coordination of metal ions in
its structure, dispensing the use of anchoring molecules for
that purpose. The carboxyl cellulose by TEMPO mediated
oxidation may be used, not as a support for metals with
catalytic activity, but as a ligand to be applied in organic
reactions, opening new possibilities of use and application
for cellulose.
Recently, the management of Suzuki-Miyaura reactions
under mild conditions using water preferentially as solvent
has been studied using sulfate silica and phosphine
palladium-platinum bi-nuclear complexes,28,29 mainly to
reduce the cost and also making an environment-friendly
reaction. Due to the insolubility in water of cellulose
materials, even carboxyl cellulose, we believe that it is
possible to use them to afford water based multi-phase
systems, substituting organic solvents which are more
dangerous, expensive and polluting. Other advantages of
cellulose based materials are their low cost, their reusability
and their biodegradability, attending to green and
sustainable principles widespread in chemistry today.30,31
Therefore, we envisage in this work the synthesis of new
catalysts based on palladium, nickel and copper complexed
with carboxyl cellulose, for application as catalysts in C−C
and C−O bond formation, in order to achieve an efficient
and environmentally friendly catalytic system, according
to the principles of green and sustainable chemistry.
Apparatus
Nuclear magnetic resonance spectrums of hydrogen
(1H NMR) and carbon (13C NMR) were obtained on a
Varian Gemini 300 MHz equipment. Chemical shifts (d)
were expressed in parts per million (ppm) and referenced
by the sign of TMS and chloroform. Infrared spectra were
obtained in a Shimadzu IR PRESTIGE-21 equipment,
using an ATR (attenuated total reflectance) cell analysing
the range from 600 to 4000 cm-1. Gas chromatography
(GC) analysis was performed using a Shimadzu GC-2104
equipment, using a shimpack semi-capillary column (5%
PhMe silicone, 30 m × 0.25 mm × 0.25 μm). The analysis
was performed by GC using the following standard
condition: T(injector) = 250 °C; T(FID detector) = 250 °C;
carrier gas = nitrogen; oven temperature program: 100 °C
for 1 min, then heated to 250 °C using a heating rate
of 20 °C min-1, and kept at this temperature for 7 min.
Thermogravimetric analysis (TGA) was performed using
a Shimadzu TG-60 equipment. During the analysis, the
system was purged with N2 flow at a rate of 50 mL min-1.
The average mass weighed was 10 mg and the measurements
were carried out between 25 and 450 °C, with a heating
rate of 20 °C min-1. ICP OES (inductively coupled plasma
optical emission spectroscopy) analysis was performed using
an iCAP 6000 series equipment from Thermo Scientific.
The samples (50 mg) were previously digested in sulfuric
acid (50 mL) at 200 °C for 1 h. The energy dispersive
X-ray fluorescence spectrometry (EDX) was carried out
in an EDX-720 equipment from Shimadzu under vacuum
conditions using a collimator of 5 mm. The isotherms
of adsorption and desorption of N2 were obtained in a
QuantaChrome Nova 2200e equipment, and the surface area
was calculated by BET (Brunauer-Emmett-Teller) method.
TEMPO-mediated oxidation
The microcrystalline cellulose was modified by
TEMPO-mediated oxidation converting the primary alcohol
from cellulose in a carboxylate group, according to the
standard procedure described below: the microcrystalline
cellulose (1 g) was suspended in a water solution (100 mL)
containing TEMPO (0.016 g, 0.1 mmol) and sodium
bromide (0.1 g, 1 mmol). The 12% NaClO solution was
adjusted to pH 10 by the addition of 0.1 M HCl solution.
The TEMPO-mediated oxidation was started by adding of
the NaClO solution (2.86 mL, 5.0 mmol) and was kept at
room temperature with stirring for 3 h. The pH was kept at
10 by adding 0.5 M NaOH solution using a pH stat until no
consumption of NaOH was observed. The reaction mixture
was centrifuged and the obtained solid was washed with
Experimental
Reagents
Commercial microcrystalline cellulose from Merck
(Art.2331), n-oxil-2,2,6,6-tetramethylpiperidine (TEMPO),
sodium bromide, a 12% sodium hypochlorite solution,
bromobenzene, bromoanisole, arylboronic acids, potassium
carbonate (K2CO3), palladium acetate (II) (Pd(OAc)2),
nickel acetate (II) (Ni(OAc)2), copper acetate (II)
(Cu(OAc)2) and other solvents and reagents were analytical
grade and used as purchased from commercial sources,
without further purification.

2066
Cellulose Oxidation and the Use of Carboxyl Cellulose Metal Complexes in Heterogeneous Catalytic Systems
J. Braz. Chem. Soc.
water and dried under reduced pressure in room temperature
(24 °C) during 12 h until no variation in the mass was
observed, leading to the sodium carboxyl cellulose (NaCC).
Also PdCC and NiCC were compared with their respective
standard catalyst acetate metal, to observe the catalytic
activity of the synthesized materials. The reactions of cross
coupling involving PdCC and NiCC were performed as
shown in Scheme 1.
Acidification of the sodium carboxyl cellulose
The acidification was carried out by adding 20 mL of
3 M solution HCl solution prepared with Milli-Q water in
1 g of NaCC obtained previously. The mixture was left under
stirring during 3 h. Thereafter the mixture was filtered and
washed with the HCl solution, followed by Milli-Q water and
then by ethanol p.a. The acidified product was called HCC.
4-OMe-Biphenyl
1H NMR (300 MHz, CDCl3) d7.54 (t, 4H, 3JHH = 9.0 Hz),
3
7.41 (t, 2H, JHH = 7.8 Hz), 7.29 (m, 1H), 6.97 (d, 2H,
3JHH = 8.7 Hz), 3.84 (s, 3H); 13C-APT (attached proton
test) NMR (75 MHz, CDCl3) d 159.1, 140.8, 133.6, 128.6,
128.1, 126.7, 126.6, 114.1, 55.3.
Preparation of metal carboxyl cellulose catalysts
4-Me-Biphenyl
1H NMR (300 MHz, CDCl3) d7.55 (d, 2H, 3JHH = 6.9 Hz),
3
3
The metal carboxyl cellulose (MCC) catalysts were
prepared by treating 1 mmol of corresponding metal acetate
(Pd(OAc)2, Ni(OAc)2 and Cu(OAc)2) with 4 mmol of the
NaCC in a mixture of methanol/acetonitrile 1:1 (4 mL). The
mixture was kept under stirring for 2 h at 60 °C. After this
period, the solvent was removed under reduced pressure
and therefore washed with water and filtered. The products,
labeled generally as metal carboxyl cellulose (MCC), were
also labeled according to the metal acetate used in the
ionic exchange, described as palladium carboxyl cellulose
(PdCC), nickel carboxyl cellulose (NiCC) and copper
carboxyl cellulose (CuCC).
7.46 (d, 2H, JHH = 8.1 Hz), 7.39 (t, 2H, JHH = 7.8 Hz),
3
7.28 (m, 1H), 7.21 (d, 2H, JHH = 7.8 Hz), 2.36 (s, 3H);
13C-APT NMR (75 MHz, CDCl3) d 141.0, 138.3, 136.9,
129.4, 128.6, 126.9, 21.0.
4-Ac-Biphenyl
1H NMR (300 MHz, CDCl3) d 8.03 (d, 2H,3JHH = 13.8
and 8.4 Hz), 7.81 (d, 2H, 3JHH = 8.7 Hz), 7.64 (m, 3H), 7.45
(m, 2H), 2.60 (s, 3H); 13C-APT NMR (75 MHz, CDCl3)
d 197.7, 145.8, 139.8, 135.7, 131.8, 129.8, 128.9, 128.8,
128.1, 127.2, 127.1, 26.6.
General procedure for C−O bond formation reaction
General procedure for Suzuki-Miyaura coupling
In a sealed Schlenk tube containing 1 mL of alcohol,
Cs2CO3 (2.0 mmol), bromobenzene (1.0 mmol), catalyst
(1.0%) and phenantroline (5.0 mol%) were added. The
reaction was stirred under argon atmosphere for 24 h at
130 °C and an aliquot was removed for GC analysis.
CuCC was used for the coupling reaction involving
heteroatoms, in which the main reagent is used also as a
solvent during the reaction.32 The reaction that followed
was similar to those described in the literature.33,34 Also a
comparison with standard catalyst cupper acetate catalyst
was performed to observe the catalytic activity of the CuCC.
The reaction was performed according to Scheme 2.
In a sealed Schlenk tube containing 3 mL of solvent,
base (1.5 mmol), arylboronic acid (0.7 mmol), catalyst
(0.5%) and aryl halide (0.5 mmol) were added. The reaction
was stirred under argon atmosphere at the programmed time
and temperature. The organic phase was extracted with
10 mL of dichloromethane and an aliquot was removed
for GC analysis.
A series of reactions were performed using different
temperature and solvents, in order to analyze the behavior
of the new catalysts and to find an optimum condition to
form the product of the coupling between the substrates.
Scheme 1. The Suzuki coupling reaction catalyzed by MCC.
Scheme 2. C−O bond formation reaction promoted by CuCC.

Vol. 28, No. 11, 2017
Martins et al.
2067
1-OPe-Phenyl
1H NMR (300 MHz, CDCl3) d 7.42 (m, 3H), 6.98 (d,
2H, 3JHH = 8.7 Hz), 4.0 (t, 2H, 3JHH = 6.5 Hz), 1.80 (m, 2H),
1.53 (m, 4H), 1.00 (t, 3H, 3JHH = 7.3 Hz); 13C-APT NMR
(75 MHz, CDCl3) d 158.7, 140.8, 126.5, 115.1, 67.7, 31.3,
20.1, 19.2, 13.8.
Results and Discussion
Cellulose oxidation characterization
During the TEMPO-mediated oxidation reaction, no
solubility of the cellulose was observed. At the end of
the reaction a light brown solid was obtained, contrasting
with the white color of its precursor. The solubility of the
NaCC material was evaluated in water, methanol, ketone,
tetrahydrofuran, dimethylsulfoxide, dichloromethane, ethyl
acetate, toluene and hexane. None of the solvents tested
were able to solubilize NaCC, showing that the material
has solubility similar to microcrystalline cellulose. Indeed,
after filtering and drying under vacuum, it was observed no
significant variation in the mass of the solid, suggesting its
completely insolubility in the evaluated solvents.
The modified functional groups in the microcrystalline
cellulose were evaluated by attenuated total reflectance
infrared spectroscopy analysis (ATR-IR). Comparing the
ATR-IR spectra of microcrystalline cellulose and NaCC
presented in Figure 1 it can be observed the appearance of
an intense absorption band at 1605 cm-1 after the treatment
with TEMPO, corresponding to the appearance of carbonyl
stretching frequency for carboxyl groups, which were
absent in microcrystalline cellulose spectra. The appearance
of carboxylate bands in the FTIR spectra of NaCC, confirms
the oxidation of the microcrystalline cellulose alcohols
groups into carboxilate.35 According to the ATR-IR data,
TEMPO-mediated oxidation was successfully applied
for the oxidation of the primary hydroxyl groups in the
carboxyl groups, as related elsewhere.36 It becomes also
clear from Figure 1 that the other regions in the ATR-IR
spectra of microcrystalline cellulose and NaCC had no
other significantly change, especially in the bands related
to 1,4-glycosides bonds (1200-1000 cm-1). This result
suggests that no other changes in the cellulose structure
were achieved during TEMPO oxidation, allowing us to
assume that the modified cellulose chain is almost the
same of the starting commercial microcrystalline cellulose.
This result was partially expected as far as it is largely
known that to undergo cellulose hydrolysis and, thus, its
depolymerization, more drastic conditions may be used.37-39
However, further studies should be done to prove no other
changes in the cellulose structure took place.
Figure 1.ATR-IR of microcrystalline cellulose before and after TEMPO-
mediated oxidation (NaCC), and the acidification of the TEMPO modified
product (HCC).
Comparing the ATR-IR spectra of NaCC and HCC in
Figure 1 it can be seen the disappearance of the band in
1605 cm-1, related to C=O stretching of sodium carboxyl
group, and the appearance of a new band in 1725 cm-1,
related to C=O stretching of carboxylic acids. This
observation evidences the complete acidification of NaCC
material. Again, no other significantly modification can be
seen in ATR-IR spectra in both obtained materials.
To quantify the conversion of alcohols into carboxyl
groups, HCC was titrated using a standard KOH solution.
Comparing the result with theoretical total amount of
hydroxyl groups in microcrystalline cellulose it was
determined a conversion of 10%. This low yield may be
due to most of the hydroxyl groups inside the cellulose
fibers and not accessible to react.
The isotherm of the synthetized material can be seen
in Figure 2. According to this analysis, NaCC has a lower
capacity as adsorbent when compared to microcrystalline
cellulose. The calculated superficial area of the materials by
BET method is 17.587 and 15.200 m2 g-1 for microcrystalline
cellulose and NaCC, respectively, showing a reduction of
the superficial area of proximally 14% after oxidation. The
isotherm of NaCC, which is similar to the microcrystalline
cellulose isotherm, adjust in the isotherm type III,40 where
the adsorbate interact more with an adsorbed layer than
with the adsorbate surface.
MCC complexes characterization
NaCC was treated with nickel, palladium and copper
salts. New solids were obtained after the treatment, each
one with characteristic colors. The NiCC had a pale
green color; PdCC has a black color; and CuCC a light
green color. Their solubility was evaluated with the same

2068
Cellulose Oxidation and the Use of Carboxyl Cellulose Metal Complexes in Heterogeneous Catalytic Systems
J. Braz. Chem. Soc.
The metal cation exchange was determined by EDX
as the proportion of sodium/metal (Na/M). The materials
treated with palladium, nickel and copper showed Na/M
ratio of 5.8, 1.0 and 1.2, respectively. Thus, the cationic
exchange yield was determined as 15, 50 and 45% for
PdCC, NiCC and CuCC, respectively. Also, ICP OES
analyses were performed to determine the total amount of
metal after the ionic exchange. The concentrations obtained
were 96, 50, and 60 mg kg-1 for PdCC, NiCC and CuCC,
respectively. Which means a concentration of 0.000902,
0.000851, and 0.000944 mmol g-1 for PdCC, NiCC and
CuCC, respectively. The variation in the EDX and ICP
data can be related to the molar mass of the cations and
also that EDX analysis occur only in the surface of the
material, however the molar amount of cations are similar
in the synthetized materials.
Figure 2. Isotherms of the NaCC material obtained using N2 gas
adsorption/desorption.
TGA analysis (Figure 4) indicates that the NaCC and
its metal complexes decompose after 200 °C, remaining
relatively stable before they reach this temperature. It was
possible to observe a small loss of mass, averaging 10%,
before reaching 200 °C, which may be related to the loss of
light compounds, such as water, adsorbed in the cellulose
structure. Between 200 and 325 °C a considerable mass loss
is observed, probably indicating a thermal decomposition
of the ligand structure.
solvents tested in NaCC and the same insolubility of the
materials were observed. It is worth mentioning that the
recovered solvents were analyzed by ICP and was observed
no detectable metal content, suggesting no significant
leaching of metals from NiCC, PdCC and CuCC. This
behavior indicates that the metal exchange does not affect
the insolubility of the modified celluloses, allowing their
application as heterogeneous catalyst.
To verify the complexation of the metal cations with the
carboxyl groups, an ATR-IR analysis was performed (see
Figure 3). The metal bound is confirmed by the enlargement
and delocation of the band related to the carboxylate group.
Indeed, the infrared data shows the delocation of the C=O
band, indicating the cationic change in the materials.
The maximium wave number of C=O band shifted from
1605 cm-1 in the NaCC to 1606, 1596, 1625 cm-1 for PdCC,
NiCC and CuCC, respectively.
Figure 4. Thermogravimetrical analysis of the NaCC and MCC materials.
Pd-CC and Ni-CC cross coupling reactions
The application of the obtained catalysts in cross-
coupling reactions was started using the palladium
carboxyl cellulose (PdCC) in the Suzuki-Miyaura reaction
for the construction of biaryl units.41-43 According to the
literature, this reaction has the advantage of the flexibility
of arylboronic acids with different functional groups, also
acting with good stability against water, oxygen and heat.41
The main results are shown in Table 1.
Figure 3. Infrared spectra of the NaCC and MCC materials.

Vol. 28, No. 11, 2017
Martins et al.
2069
Table 1. Values of variation parameters in Suzuki coupling reactions catalyzed by MCC
entry
1a
2a
3a
4a
5a
6a
7a
8a,c
9a,c
10a
11a
12a
13b
14b
15b,g
16b,g
Metal
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Ni
Solvent
H2O/DMFd
DMF
Temperature / °C
Yielde / %
100
20
HC yieldf / %
80
80
< 1
< 1
< 1
< 1
< 1
< 1
< 1
2
MeOH
toluene
THF
80
94
80
25
80
18
H2O
80
25
H2O/MeOHd
MeOH
DMF
H2O/DMFd
MeOH
H2O
80
93
80
100
76
80
2
30
92
< 1
< 1
< 1
< 1
5
30
27
30
11
dioxane
toluene
dioxane
toluene
130
130
130
130
5
Ni
40
Ni
< 1
traces
Ni
2
1
aReaction conditions: 0.5 mmol of bromobenzene, 0.7 mmol of 4-methoxyphenylboronic acid, 1.5 mmol of K2CO3, 0.5% of catalyst, 3 mL of solvent,
1 h of reaction under argon atmosphere;breaction conditions: 1.0 mmol of 4-bromoanisole, 1.2 mmol of phenylboronic acid, 2.0 mmol of K2CO3, 1.0% of
catalyst, 4.0 mol% of triphenylphosfine, 3 mL of solvent, at 130 °C, 24 h of reaction under argon atmosphere; cusing Pd(OAc)2; dproportion between the
solvents of 1:1; eyield of GC based on aryl halide; fyield of homocoupling of arylboronic acid; gusing Ni(OAc)2.
First, we investigated the cross-coupling of
bromobenzene with 4-methoxyphenylboronic acid at
80 °C and 1 h of reaction, and high conversion on the
cross-coupling product was obtained using a mixture of
H2O/DMF or methanol as solvent (Table 1, entries 1 and
3). However, when using DMF or H2O separately, low
conversion was observed (Table 1, entries 2 and 6). Low
yields were observed when less polar solvents such as THF
or toluene were used (Table 1, entries 4 and 5). When the
reaction was carried out with a mixture H2O/methanol
(1:1), a higher yield was also obtained (Table 1, entry 7).
These results indicate that a suitable polarity is necessary
to allow the interaction between the substrate and the
catalyst. For comparison, Pd(OAc)2 was also employed
as a catalyst and gave very good yields but also a higher
content of homocoupling product (Table 1, entries 8 and 9).
Then we tested the catalyst at low temperature (Table 1,
entries 10-12). We were delighted to see that, when using a
mixture of H2O/DMF as solvent, PdCC is able to perform
Suzuki cross-coupling at low temperature (30 °C) and in
a short time (1 h).
products in quantitative yield (Table 2, entries 1, 3 and 4).
Very low yield was observed for the 4-chloroanisole
(Table 2, entry 2), an extremely deactivated substrate that
normally requires the addition of special ligands to be
coupled, as related in literature.44 We also evaluated the
steric effect, first using p-, m- and o-bromotoluene. At
30 °C, o-bromotoluene gave a lower yield (60%, Table 2,
entry 7). However, o-bromotoluene can be quantitatively
coupled by raising the temperature to 80 °C (Table 2,
entry 8). The system was sensitive to steric effects. Indeed,
steric-demanding combinations involving two or three
substitutions leads to low yields (Table 2, entries 9-11).
Again, these are very challenging substrates for the Suzuki
cross-coupling, where only the addition of a very specific
ligand can effectively promote the coupling reaction.45
Nickel carboxyl cellulose (NiCC) was also evaluated
for the Suzuki coupling reactions.46 First, a test was
performed for 6 h in the absence of ligands; however, no
coupling product was formed. Based on this preliminary
result for this reaction, it was performed again for a
longer time, according to the literature, in the presence
of triphenylphosphine. To understand the behavior of the
catalyst, two solvents with different polarities based on the
previous study with PdCC (Table 1, entries 13 and 14) were
used. Using dioxane as solvent, no satisfactory result was
obtained, achieving only 10% yield. On the other hand,
when using toluene as solvent, the coupling product yield
increased to 40%.
To evaluate the scope and limitations of this procedure,
the reactions of some representative aryl halides and
arylboronic acids were examined using PdCC in H2O/DMF
at 30 °C for 1 h (Table 2). Iodobenzene and both the
electron-rich 4-bromonisole and the electron-poor
4-bromoacetophenone are efficiently coupled in the
presence of PdCC to provide the corresponding biaryl

2070
Cellulose Oxidation and the Use of Carboxyl Cellulose Metal Complexes in Heterogeneous Catalytic Systems
J. Braz. Chem. Soc.
Table 2. Variation of the substrate in the reactions of Suzuki with PdCCa
entry
1
Temperature / °C
X
I
R
R’
Yieldb / %
30
30
30
30
30
30
30
80
80
80
80
H
4-OCH3
100
2
2
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Br
4-OCH3
4-OCH3
H3CC=O
4-CH3
H
H
3
100
100
79
71
60
100
22
14
1
4
H
5
H
6
3-CH3
H
7
2-CH3
H
8
2-CH3
H
9
2-CH3
2-CH3
H
10
11
2,4,6-CH3
2,4,6-CH3
2-CH3
aConditions of reactions: 0.5 mmol of aryl halide, 0.7 mmol of arylboronic acid, 1.5 mmol of K2CO3, 0.5% of PdCC, 3 mL of H2O/DMF (1:1), 1 h of
reaction under argon atmosphere;byield of GC based on aryl halide. R and R’ are represented in the Scheme 1.
The observed reaction effect of the cellulose matrix was
carried out under the same conditions using Ni(OAc)2 as
catalyst (Table 1, entries 15 and 16). It was observed that
virtually no reaction occurred, evidencing again the role of
cellulose matrix in maintaining a high catalytic activity for
the coupling reaction. The behavior of NiCC is opposite
to the PdCC front of solvent polarity, probably due to
the lower lability of nickel. For this case, the oxidative
addition step has a higher probability of occurring with
the less-coordinating solvent. The ICP analysis showed
that no nickel leached from the catalyst, as occurred with
palladium.
The general mechanism for the coupling reactions with
Pd and Ni is shown as a simplified catalytic cycle of three
steps: oxidative addition, transmetallation and reductive
elimination (Scheme 3). The catalytic cycle begins in
the oxidative addition of the electrophile to the metal,
oxidizing the M(0) to M(II); this step is crucial to the
speed of most of these reactions as its ligands exert enough
influence for the CC ligand to participate in increasing the
yield obtained, mainly in the reaction with nickel. In the
transmetallation step, the transfer of an organic group to the
metal core involved in the catalysis occurs. The final step
of the catalytic cycle is the reductive elimination, where
the formation of the new carbon-carbon bond and groups
that are joined must be in the cis position; then, it will
return to the metal oxidation state (0), thus reestablishing
the catalytic cycle.
After another insertion of another arylboronic acid, they
can homocouple by eliminative reduction.
CuCC C−O bound cross coupling reactions
The CuCC performance was evaluated for the reaction
of bromobenzene using methanol as a reactant and solvent
for 6 h with and without phenanthroline as ligand (Table 3,
entries 1 and 2, respectively).Although the presence of the
CC ligand gave better yields, they were very low, even after
24 h (Table 3, entry 3). Low yields were also obtained for
the reaction of n-pentanol (Table 3, entries 4-9). For the
long-chain alcohol, a significant amount of by-product amyl
ether was observed (up to 8%).
Due to the low activity of bromobenzene, we used
iodobenzene (Table 3, entries 10 and 11). We were delighted
to see that the quantitative yield of coupling product was
obtained after 24 h (entry 11). In addition, the formation of
the ether by-product was minimized (< 1%). We also ran
some initial tests using N-benzylmethylamine in place of
the alcohols. However, no formation of the C−N coupling
product was observed. More studies are needed for the use
of the CuCC in the formation of C−N bonds.
It is important to highlight the increased yielding
obtained when using Pd, Ni or Cu ions complexed with
carboxyl cellulose ligand, when comparing to the standard
acetates metal salts, usually used for comparison reasons
in the literature. It is important to highlight that among
the several classes of ligands already studied in more
than 3 thousand works available in the literature this work
describes for the first time the application of a cellulose
derivative as ligand for Suzuki cross-coupling reactions
(see for instance the very recent review of Suzuki catalysts
by Maluenda and Navarro).48
The homocoupling reactions occurs, though on a minor
scale, because the additive oxidation of aryl halides in
Pd and Ni cores is kinetically faster. The homocoupling
mechanism is suggested to involve the entry of aryl boronic
acids in the coordination sphere of the metal by insertion,
mediated by a strong nucleophilic ligand such as HO-.

Vol. 28, No. 11, 2017
Martins et al.
2071
Scheme 3. Textbook proposed catalytic cycle for coupling reaction using Ni and Pd as catalyst.47
Table 3. Results for C−O bond formation reaction promoted by CuCCa
entry
1
PhX
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
PhBr
PhI
ROH
time / h
Ph-OR yieldf / %
ROR yieldg / %
MeOH
6
6
6
3
−
−
2b
MeOH
3
MeOH
24
6
6
−
4
n-PeOH
n-PeOH
n-PeOH
n-PeOH
n-PeOH
n-PeOH
n-PeOH
n-PeOH
4
6
5e
6
< 1
11
7
6
6
24
24
24
24
6
8
7b
8c
9d
10
11
7
7
2
< 1
81
100
−
< 1
PhI
24
< 1
aReaction conditions: 1.0 mmol of phenyl halide, 1 mL of alcohol, 2.0 mmol of Cs2CO3, 5.0 mol% of phenanthroline, 1.0% of CuCC, 24 h at 130 °C,
under argon atmosphere; bwithout phenanthroline; cwith Cu(OAc)2; daccomplished with 1.4 mmol of 1-penthanol and 1 mL of toluene as solvent; ereaction
accomplished at 60 °C; fyield of GC based on aryl halide; gyield etherification of alcohols.
Conclusions
The efficient and environmentally friendly methodology
that was developed contributes to the advancement of
sustainable chemistry adding value to cellulose. We are
currently deepening our studies in the use of these new
materials, as well as using other metal cations, for other
reactions, such as biodiesel production and modifications,
and we believe that cellulose modified ligands may be
further used in several other environmental friendly
catalytic systems.
In summary, we report the preparation of new catalytic
systems based on palladium, nickel and copper complexed
in modified commercial cellulose. These new catalysts
can be used for application in organic reactions involving
C−C and C−O bond formation to obtain products of great
importance for the chemical and pharmaceutical industry
with a satisfactory activity under heterogeneous conditions.

2072
Cellulose Oxidation and the Use of Carboxyl Cellulose Metal Complexes in Heterogeneous Catalytic Systems
J. Braz. Chem. Soc.
Acknowledgments
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The authors are in debt to CAPES (PROCAD project
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CAPES for post-doctoral financial support, P. A. Z. S. and
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Submitted: December 10, 2016
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FAPERGS/CAPES has sponsored the publication of this article.