Continuous-Flow Palladium-Catalyzed Synthesis of Cyclohexanones from Phenols using Sodium Formate as a Safe Hydrogen Source

Article abstract of DOI:10.1002/cctc.201701922

We report a procedure for the continuous-flow production of cyclohexanone from phenol on the basis of the use of sodium formate as a biomass-derived source of hydrogen and Pd/C as an easily accessible catalyst system. The reaction worked in water at pH 12.0 at 90 °C. By setting a packed reactor charged with the Pd/C catalyst (10 wt %) at a flow rate of 0.5 mL min^?1, we achieved continuous-flow production of cyclohexanone in high yield with high selectivity and productivity.

Full text of DOI:10.1002/cctc.201701922

Accepted Article
Title: Continuous-flow Pd-catalyzed synthesis of cyclohexanones from
phenols using sodium formate as a safe hydrogen source
Authors: Luigi Vaccaro, Federica Valentini, Niccolò Santillo, Chiara
Petrucci, Daniela Lanari, Elena Petricci, and Maurizio Taddei
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ChemCatChem
10.1002/cctc.201701922
COMMUNICATION
Continuous-flow Pd-catalyzed synthesis of cyclohexanones from
phenols using sodium formate as a safe hydrogen source
[
a]
[b]
[a]
[a]
[b]
Federica Valentini, Niccolò Santillo, Chiara Petrucci, Daniela Lanari, Elena Petricci, Maurizio
[b]
[a]
Taddei and Luigi Vaccaro*
Abstract: We report a procedure for the continuous flow production
of cyclohexanone from phenol, based on the use of sodium formate
as a biomass derived source of hydrogen and on Pd/C as an easily
accessible catalytic system. The reaction works in water at pH =
phenol is based on controlling the desorption of cyclohexanone
from the catalyst surface before further hydrogenation leads to
cyclohexanol.
[9]
1
2.0 and at 90 °C. by setting a packed reactor charged with the
-1
catalyst Pd/C (10wt%) at a flow rate of 0.5 mL min we achieved a
continuous flow production of cyclohexanone with high yields,
selectivity and productivity.
Phenols, mostly in their polymeric forms in lignin, are the second
most prevalent naturally occurring structural units of renewable
biomass on the planet, and they are regarded possibly valuable
materials deriving from biomass treatment. Indeed removal of
the functional groups present in lignin, yields simple aromatic
compounds such as phenol, benzene, toluene, and xylene.
Consequently, application of phenols as commodity chemicals
Scheme 1.Reaction steps in a typical phenol hydrogenation.
[1]
or substrates for useful transformation is highly desirable.
The use of formic acid derivatives as hydrogen source in
combination with a palladium catalyst, is a promising safer and
sustainable alternative to classic methods. Formates are stable,
Cyclohexanone is of the main commodities of chemical industry
feeding the production of caprolactam and adipic acid, which in
turn are transformed into Nylon 6, Nylon 6,6 and polyamide
[10]
[2]
non-toxic and they can be obtained from biomass processing.
resin. Large production of cyclohexanone is based either on
cyclohexane oxidation under Co catalysis or phenol partial
hydrogenation in the presence of different transition metal
catalysts. On a different approach, starting from phenol, the
industrial process toward cyclohexanone comprises the initial
reductive step accessing cyclohexanol which is further
dehydrogenated to cyclohexanone in a high temperature gas-
phase Pd or Pt catalyzed process. In order to define milder and
energy efficient one-step processes, the use of selective
homogeneous and heterogeneous catalysts has been
investigated in liquid phase resulting in with many successful
Formic acid derivatives have also been proposed as hydrogen
storage materials, as they are suitable for safe transportation
[11]
and handling.
formic acid, sodium formate
Some examples of phenol reduction using
[12]
[13,14]
[15]
or potassium formate in
batch conditions have been recently reported. Although very
attractive, some of these protocols feature some limitations, as
[12]
the requirements for inert atmosphere or microwave
[14]
heating. In addition, complex catalytic systems requiring
specific procedures for their preparation, are often necessary to
achieve high efficiency and good selectivity towards
[13]
[3]
[4]
[5]
[6]
cyclohexanone production.
Following our interest in developing sustainable protocols based
examples mainly based on single or mixed Pd, Pt, Ru, Rh
[7]
[8]
and Ni catalystson different supports.
[16]
on the use of safe media, heterogeneous catalysis
and the
Considering commonly proposed mechanism for the
hydrogenation of phenol on supported palladium catalysts,
reduction occurs on the phenolate ion adsorbed on the support
in proximity of the metal particles that are responsible for the
hydrogen activation. The chemical strategy to selectively reduce
[17]
application of flow technology, we report herein our approach
towards the definition of a continuous-flow protocol using
commercially available Pd/C for the catalyzed selective transfer
hydrogenation of phenol to cyclohexanone in water, using
sodium formate as hydrogen source.
In a preliminary optimization study in batch, we investigated the
best reaction conditions suitable for a further transfer to a flow
protocol. Based on literature data, Pd/C was selected as the
representative commercially available and cheap heterogeneous
catalyst to be used in water. The selection of water as medium,
beside its environmentally benign and safe nature, allows also
[
a]
Federica Valentini, Dr. Chiara Petrucci,Dr. Daniela Lanari,Prof. Dr.
Luigi Vaccaro
Laboratory of Green S.O.C. – Dipartimento di Chimica, biologia e
Biotecnologie
Università degli Studi di Perugia
Via Elce di Sotto 8, 06123 – Perugia – IT
E-mail: luigi.vaccaro@unipg.it; Web: www.dcbb.unipg.it/greensoc
Niccolò Santillo,Dr.Elena Petricci, Prof. Dr. Maurizio Taddei,
Dipartimento di Biotecnologie, Chimica e Farmacia
Università degli Studi di Siena
[18,19]
an efficient dissolution of H
2
.
In addition, we also based our
[b]
approach on the fact that phenol (1) is completely soluble in
water at temperatures higher than 66 °C, while cyclohexanone
[20]
(
3) and cyclohexanol (4) are not, thus facilitating the
Via A. Moro 2, 53100 – Siena – IT
separation of the products from the aqueous phase at the end of
the reaction.
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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COMMUNICATION
Pd/C (5 mol%)
(see SI).Using strictly equimolar ratio, 93% of conversion and
97% selectivity were obtained after 2.5 h of reaction at 90 °C
(See SI).
OH
O
OH
formic acid or formate
H O 90°C
2
+
The influence of the natureof the base employed was also
investigated by heating the reaction at pH 12.0 for 30 min at 90 °C
in the presence of different hydroxides (Figure 3). Exclusively
NaOH gave good results in terms of conversion and
selectivity,underlining a “cation” effect in the process. This
observation may also indicate that the reaction could occur with
via absorption of the phenolate ion on the support close to
1
3
4
Scheme 2.Screening of the reaction parameters.
When formic acid was employed as the hydrogen source in water,
a complete conversion of phenol was observed at 90 °C after 1 h
but, unfortunately, only traces of cyclohexanone (3) were obtained
while cyclohexanol was the prevailing product (95% of the
converted compound). Then, sodium formate was employed and
again complete conversion was achieved but still with an
unsatisfactory selectivity (48/ 52 ratio of 3/ 4).
H
2
adsorbed on Pdas in this case, an influence of the cation size
could be expected.
100
80
60
We therefore decided to take under consideration the pH ofthe
reaction mixture by measuring and varying it. The experiments
design was based on the preparation of a 0.2 M solution of phenol
in water plus 2.5 equivs of sodium formate resulting in a mixture
with a pH of 6.90. Then, addition of a 5 M solution of NaOH
allowed to adjust the pH to the desired values and then reaction
mixture heated at 90 °C for 30 min.
With the increase of pH, selectivity towards cyclohexanone
formation was also improved and therefore we decided to study
more in details the influence of pH on the process. Results in
terms of conversion of phenol and selectivity cyclohexanone (3)
versus cyclohexanol (4) are reported in Figure 1.
4
0
0
0
2
pH 10.0 pH 12.0 pH 10.0 pH 12.0
pH 10.0 pH 12.0
t:2.5 h t:2.5 h
t:30 min t:30 min
t:1.5 h
t:1.5 h
conv (%)
sel (%)
Figure 2.Influence of time and pH on phenol conversion and selectivity in
cyclohexanone formation.
100
100
80
60
40
20
0
80
60
40
20
0
pH 7.0
pH 9.0
pH 10.0
pH 11.0
pH 12.0
pH 13.0
NaOH
NH4OH
Bu4NOH
sel (%)
KOH
conv (%)
sel (%)
conv (%)
Figure 1.Influence of pH on phenol conversion and selectivity in
cyclohexanone formation.
Figure 3. Influence of the base on phenol conversion and selectivity in
cyclohexanone formation.
The increase of the pH of the medium proved to be crucial for
the selectivity of the hydrogenation of phenol to cyclohexanone
and a 95% conversion/98 % selectivity was achieved at pH =
The conclusion of the experiments in batch conditions
demonstrated that sodium formate is a suitable source of H in a
2
12.0. However, acceptable results were obtained also in the pH
process where Pd/C decomposes the formate and catalyzes the
selective reduction of the phenolate ion generated at pH 12.0.
In view of designing the flow reactor for the continuous flow
protocol, the reaction was carried out with a larger amount of the
Pd catalyst (50 mol%), observing always a high conversion and
a good selectivity after only 5 min of reaction time (Figure 4).
The continuous flow experiment was set by preparing a packed
glass reactor containing Pd/C (1.2 g, 10%wt) dispersed over
range between 10 and 12. At lower pH poorer selectivity was
observed while at higher pH conditions conversion was limited.
We also performed different experiments with variable reaction
times (Figure 2). At pH 12.0, after 1.5 or 2.5 h an evident
increase of the cyclohexanol formed was observed (Figure 2).
To limit further reduction of cyclohexanone or its enolate ion, we
reduced the excess of sodium formate employed in the reaction
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COMMUNICATION
glass spheres and charging the catalyst in a glass column
located inside to a thermostated bath at 90 °C. The mixture of
phenol (1) and sodium formate in water was adjusted to pH
process 50 mmol of phenol, which represents a noticeable
improvement with respect of our best batch protocol. With the
disclosed flow protocol, a TON value of 70.2 was achieved,
corresponding to a TOF value of 11.7 h and further extension
of the reaction time would clearly lead to higher productivity.
-1
12.0with the addition of aqueous NaOH 5M and placed in a flask
acting as a reservoir (Scheme 3). The reservoir was connected
to a HPLC pump and the aqueous mixture was pumped through
-
the catalyst reactor (heated at 90°C) at a flow rate of 0.5 mL min
.
Table 1.Flow hydrogenation on various substrates.
1
2
As during the reaction gaseous H was formed, a back-
pressure regulator (BPR) was placed at the end of the catalysts
column, setting the pressure to 5 psi.
100
80
60
40
20
0
Entry
Substrate
Residence
time (min)
BPR
(psi)
T
(°C)
C
(%)
S
(%)
[
a]
[a]
pH 7.0
pH 10.0
pH 12.0
1
2
3
4
4
5
65
65
65
90
30
50
90
95
-
7
20
40
40
87
85
70
5a
conv (%)
sel (%)
15
15
Figure 4.Hydrogenation of phenol over 50 mol% of Pd/C after 5 min reaction
time.
5
6
7
7
7
9
20
90
90
65
50
15
70
83
-
5b
100
40
termostatatedchamber90°C
76
8
9
7
100
40
90
90
18
50
-
5c
Pd/C packed reactor
BPR
15
89
[a] (C) Conversion and (S) Selectivity data were measured by GLC analyses
Considering the results obtained with phenol, the flow protocol in
Scheme 3 was extended to other substrates relevant in the
biomass valorisation research, as they are models of phenol
derivatives obtained from lignin depolymerisation (Table 1). With
these substrates, we tried to optimize the conversion and the
selectivity of the process by varying several parameters, such as
the residence time in the catalyst columns, the BPR used to
control hydrogen pressure in the reactor and temperature. In the
case of guaiacol (5b) and 2-cresol (5c) the substrate was not
completely soluble in water, therefore the mixture was kept
under stirring and pumped as an emulsion. From literature, the
selectivity in the hydrogenation of catechol (5a) and cresols is
HCOONa
H O
2
pH 12.0
Phase
separation
Pure
2
H O
HCOO Na
-
+
Scheme 3.Flow reactor used for the hydrogenation of 1.
Under these conditions, 90 % conversion of 1 was achieved with
00% selectivity for the formation of desired cyclohexanone (3).
1
The product was recovered through extraction with heptane,
while most of the unreacted phenol was retained in the aqueous
phase, and it was eventually removed from the organic phase by
dilute NaOH wash. Isolation of pure product 3 was achieved
after evaporation of the organic solvent.
[21]
known to be an issue both when molecular hydrogen or formic
[14]
acid
are used. Also in continuous flow, when catechol (5a)
With this setup and using up to 20 mmol of phenol were
converted before observing a drop in the conversion from 90 to
was selected as substrate, conversion and selectivity obtained
with phenol were not achievable since over-hydrogenation to
1,2-cyclohexanediol occurred to a considerable extent. The
same issue was observed for guaiacol (5b) and 2-cresol (5c).
Acceptable selectivity was obtained only at a low level of
conversion (Table 1, entry 5), while a prolonged residence time
led to higher conversion but lower selectivity (Table 1, entry 7).
The selection of the pressure limit of the BPR has effect on the
outcome of the reaction. In fact, when low pressure (5 psi) or
high pressure (100 psi) were employed only minor conversion
65 %. However, after a simple washing of the catalyst column
with water (5 times the column volume), the catalyst activity was
recovered and the reaction proceeded again with ca. 90%
conversion. Probably, this reduction of conversion was due to
the deposition of some bicarbonate salts coming from sodium
formate oxidation.
During representatively 6 hours of operation, 5 g of phenol were
converted in flow allowing 3.9 gr of pure cyclohexanone to be
isolated inan overall 80 % yield. It is noteworthy that under
continuous flow operation, only 1.1 mol% of Pd were required to
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were obtained (Table 1, entries 1, 6, 8) while best results were
gained at 40 psi.
[1]
[a] J. Zakzeski, P. C. A. Bruijnincx, A. L. Jongerius, B. M. Weckhuysen,
Chem. Rev., 2010, 110, 3552–3599; [b] A. Corma, S. Iborra, A. Velty,
Chem. Rev., 2007, 107, 2411–2502.
In conclusion, we have reported the first example of the
application of flow technology to the transfer hydrogenation of
phenol (1) to cyclohexanone (3), using sodium formate as safe
and bioderived hydrogen source in water. The application of a
packed continuous flow reactor allowed the prolonged use of the
catalyst (Pd/C), ensuring a good productivity and giving pure
cyclohexanone in an efficient protocol. Although a further
optimization will be required for substituted phenols these results
confirm that transfer hydrogenation process represents an
environmentally benign and safe alternative to classical phenol
hydrogenation protocols, employing molecular hydrogen, and
this report will promote further investigation in this direction to
define additional reactor settings and to access the selective
reduction of variously substituted phenols.
[
2]
3]
M. T. Musser, in Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-
VCH Verlag GmbH & Co. KGaA, 2011.
[
Some selected examples: [a] F. Zhang, S. Chen, H. Li, X.-M. Zhang
and H. Yang, RSC Adv., 2015, 5, 102811–102817.[b] Z. Li, R. S.
Assary, A. C. Atesin, L. A. Curtiss, T. J. Marks, J. Am. Chem. Soc.2014,
136, 104–107. [c] D. Zhang, Y. Guan, E. J. M. Hensen, L. Chen and Y.
Wang, Catal. Commun., 2013, 41, 47–51. [d] A. Chen, G. Zhao, J.
Chen, L. Chen and Y. Yu, RSC Adv., 2013, 3, 4171–4175.[e] Y. Wang,
J. Yao, H. Li, D. Su and M. Antonietti, J. Am. Chem. Soc., 2011, 133,
2362–2365. [f] Y. Pérez, M. Fajardo and A. Corma, Catal. Commun.,
2011, 12, 1071–1074. [g] J. Matos and A. Corma, Appl. Catal. Gen.,
2011, 404, 103–112. [h] C. Zhao, Y. Kou, A. A. Lemonidou, X. B. Li, J.
A: Lercher, Angew. Chem. Int. Ed.2009, 48, 3987–3990.
[4]
Some selected examples: [a] H. Ohta, H. Kobayashi, K. Hara, A.
Fukuoka, Chem. Commun.2011,47, 12209–12211. [b] X. L. Zhu, L. L.
Lobban, R. G. Mallinson, D. E. Resasco, J. Catal.2011, 281, 21–29. [c]
D. Y. Hong, S. J. Miller, P. K. Agrawal, C. W. Jones, Chem.
Commun.2010, 46, 1038–1040.
Experimental Section
[5]
Some selected examples: [a] X. Cui, A.-E. Surkus, K. Junge, C. Topf, J.
Radnik, C. Kreyenschulte, M. Beller, Nature Commun.2016, 7, 11326.
Typical procedure for the hydrogenation in batch: Phenol 1 (0.8 mmol, 75
mg), sodium formate (2.5 eq, 120 mg) and water (0.2 M, 4 mL) were
placed in a screw capped vial, equipped with a stirring bar. The pH of the
mixture was adjusted to 12.0 by adding NaOH (aq 5M). Pd/C (10 wt%, 5
mol%, 42 mg) was added and the reaction mixture was stirred at 90 °C
for 30 minutes. After reaction completion, the catalyst was filtered off and
the mixture was extracted with heptane, then the combined organic
[
b] A. Maximov, A. Zolotukhina, V. Murzin, E. Karakhanov and E.
Rosenberg, ChemCatChem, 2015, 7, 1197–1210; [c] K. L. Luska, P.
Migowski, S. El Sayed, W. Leitner, Angew. Chem. Int. Ed.2015, 54,
1
5750–15755. [d] N. Yan, Y. A. Yuan, R. Dykeman, Y. A. Kou, P. J.
Dyson, Angew. Chem. Int. Ed.2010, 49, 5549–5553. [e] H. J. Xu, K.
Wang, H. Zhang, L. Hao, J. Xu, Z Liu, Catal. Sci. Technol.2014, 4,
2
658–2663. [f] J. M. Nichols, L. M. Bishop, R. G. Bergman, J. A. Ellman,
2 4
layers were dried over anhydrous Na SO . The product was recovered
after evaporation of the solvent under reduced pressure.
J. Am. Chem. Soc.2010, 132, 16725–16725.
6
[a] N. Singh, Y. Song, O. Y. Gutiérrez, D. M. Camaioni, C. T. Campbell,
J. A. Lercher, ACS Catal.,2016, 6, 7466–7470. [b] S. Kuklin, A.
Maximov, A. Zolotukhina, E. Karakhanova, Catal. Commun., 2016, 73,
63–68, [c] I. E. Ertas, M. Gulcan, A. Bulut, M. Yurderi and M.
Zahmakiran, J. Mol. Catal. Chem., 2015, 410, 209–220. [d] M.
Chatterjee, T. Ishizaka, A. Suzuki, H. Kawanami, Chem. Commun.2013,
49, 4567–4569.
Typical procedure for the flow synthesis of 3: A premixed mixture of
phenol 1 and sodium formate (2.5 eq) in H O (0.2 M) was prepared in a
2
flask with the function of reservoir and pH was adjusted to 12.0 with the
addition of aqueous NaOH (5M). Pd/C (10 wt%, 1.2 g) was dispersed in
0.5-1 mm diameter solid glass beads and charged in two Omnifit glass
columns (600 mg each); the equipment was connected, by using the
appropriate tubes, to the pump and a 5 psi backpressure regulator was
placed on the outlet tube. The catalyst columns were placed into a
thermostated box and the reaction mixture was continuously pumped
7
Some selected examples: J. Zhang, J. Teo, X. Chen, H. Asakura, T.
Tanaka, K. Teramura, N. Yan, ACS Catal.2014, 4, 1574–1583. P.
Ferrini, R: Rinaldi, Angew. Chem. Int. Ed.2014, 53, 8634–8639. M.
Zaheer, J. Hermannsdorfer, W. P. Kretschmer, G. Motz, R. Kempe,
ChemCatChem2014, 6, 91–95. M. R. Sturgeon, M. H. O'Brien, P. N.
Ciesielski, R. Katahira, J. S. Kruger, S. C. Chmely, J. Hamlin, K.
Lawrence, G. B. Hunsinger, T. D. Foust, R. M. Baldwin, M. J. Biddy, G.
T. Beckham, Green Chem.2014, 16, 824–835. V. Molinari, C. Giordano,
M. Antonietti, D. Esposito, J. Am. Chem. Soc.2014, 136, 1758–1761. J.
Zhang, H. Asakura, J. van Rijn, J. Yang, P. Duchesne, B. Zhang, X.
Chen, P. Zhang, M. Saeys, N. Yan, Green Chem.2014, 16, 2432–2437.
H. Shafaghat, P. S. Rezaei and W. M. A. W. Daud, RSC Adv., 2015, 5,
(residence time 7 min) through the catalyst columns at 90 °C. The
conversion of 1 was periodically monitored by GLC. The resulting
aqueous mixture was extracted with heptane, then the combined organic
2 4
layers were dried over anhydrous Na SO . The product 3 was obtained in
80 % yield after evaporation of the solvent under reduced pressure.
8
Acknowledgements
33990–33998.
9
S. Scirè, S. Minicò and C. Crisafulli, Appl. Catal. Gen., 2002, 235, 21–
31.
The Università degli Studi di Perugia and the Università degli
Studi di Siena are acknowledged for financial support. We
gratefully acknowledge the “Fondazione Cassa di Risparmio di
Perugia” for financial supporting through the project
10
D. J. Hayes, S. Fitzpatrick, M. H. B. Hayes and J. R. H. Ross, in
Biorefineries-Industrial Processes and Products, eds. B. Kamm, P. R.
Gruber and M. Kamm, Wiley-VCH Verlag GmbH, 2005, pp. 139–164.
M. Yadav and Q. Xu, Energy Environ. Sci., 2012, 5, 9698–9725.
D. Zhang, F. Ye, T. Xue, Y. Guan and Y. M. Wang, Catal. Today, 2014,
1
1
2
“
Manipolazione di biomassa lignocellulosica per la produzione di
1
additivi per biocarburanti”, Codice Progetto: 2016.0060.021
RICERCA SCIENTIFICA E TECNOLOGICA.
2
34, 133–138.
A. Chen, Y. Li, J. Chen, G. Zhao, L. Ma and Y. Yu, ChemPlusChem,
013, 78, 1370–1378.
H. Cheng, R. Liu, Q. Wang, C. Wu, Y. Yu and F. Zhao, New J. Chem.,
012, 36, 1085–1090.
1
3
4
2
1
Keywords:phenols•hydrogenation •sodium formate 3
2
•continuous-flow chemistry
1
5
6
R. D. Patil and Y. Sasson, Appl. Catal. Gen., 2015, 499, 227–231.
[a] D. Lanari, O. Piermatti, C. Morozzi, S. Santoro, L. Vaccaro,
Synthesis, 2017, 49, 973–980; [b] V. Kozell, M. McLaughlin, G.
1
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ChemCatChem
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COMMUNICATION
Strappaveccia, S. Santoro, L. A. Bivona, C. Aprile, M. Gruttadauria, L.
Vaccaro, ACS Sustainable Chem. Eng.2016, 4, 7209–7216; [c] D.
Rasina, A. Kahler-Quesada, S. Ziarelli, S. Warratz, H. Cao, S. Santoro,
L. Ackermann, L. Vaccaro, Green Chem.2016, 18, 5025–5030, [d] X.
Tian, F. Yang, D. Rasina, S. Warratz, M. Bauer, F. Ferlin. L. Vaccaro, L.
Ackermann, Chem. Commun.2016, 52, 9777–9780; [e] S. Santoro, S.
Kozhushkov, L. Ackermann, L. Vaccaro, Green Chem., 2016, 18,
2017; [c] V. R. Jumde, E. Petricci, C. Petrucci, N. Santillo, M. Taddei, L.
Vaccaro, Org. Lett.2015, 17, 3990−3993.
18
19
20
21
Purwanto, R. M. Deshpande, R. V. Chaudhari and H. Delmas, J. Chem.
Eng. Data, 1996, 41, 1414–1417.
J. Zhong, J. Chen and L. Chen, Catal. Sci. Technol., 2014, 4, 3555–
3569.
Y. Xiang, L. Ma, C. Lu, Q. Zhang and X. Li, Green Chem., 2008, 10,
939–943.
3
471–3493.
[a] F. Ferlin, S. Santoro, L. Ackermann, L. Vaccaro, Green Chem., 2017,
9, 2510–2514; [b] “Sustainable Flow Chemistry: Methods and
Applications”, L. Vaccaro: editor Wiley-VCH, Weinheim, Germany,
17
C.-J. Lin, S.-H. Huang, N.-C. Lai and C.-M. Yang, ACS Catal., 2015, 5,
4121–4129
1
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COMMUNICATION
COMMUNICATION
A continuous flow protocol for the
production of cyclohexanone from
phenol, has been reported by using
sodium formate as a biomass derived
source of hydrogen and on Pd/C as
an easily accessible catalytic system.
Federica Valentini, Niccolò
termostatatedchamber 90°C
Santillo,Chiara Petrucci, Daniela Lanari,
Elena Petricci, Maurizio Taddei,* Luigi
Vaccaro*
Pd/C packed reactor
BPR
Page No. – Page No.
HCOONa
H O
2
pH 12.0
Phase
separation
Pure
Continuous-flow Pd-catalyzed
synthesis of cyclohexanones from
phenols using sodium formate as a
safe hydrogen source
2
H O
HCOO Na
- +
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