Novel access to verbenone via ruthenium nanoparticles-catalyzed oxidation of Α-pinene in neat water

Article abstract of DOI:10.1016/j.apcata.2017.11.016

Aqueous suspensions of Ru(0) nanoparticles, stabilized with hydroxyethylammonium salts and possessing sizes around 2 nm, proved to be active and selective in the mild oxidation of α-pinene in the presence of tert-butylhydroperoxide, in neat water. Verbenone, a product of great interest for fine chemistry, was obtained as major product with yield up to 41% under optimized conditions. 2-hydroxy-3-pinanone was identified as a co-product of the reaction, but with very low amount (<7%). Kinetic investigations allowed determining the potential reaction intermediates and by-products. Moreover, mechanistic studies with radical scavengers confirmed that α-pinene oxidation mainly implies both carbon- and oxygen-centered radicals.

Full text of DOI:10.1016/j.apcata.2017.11.016

Accepted Manuscript
Title: Novel access to verbenone via ruthenium
nanoparticles-catalyzed oxidation of ␣-pinene in neat water
Authors: Mariem Rauchdi, Mustapha Ait Ali, Alain Roucoux,
Audrey Denicourt-Nowicki
PII:
S0926-860X(17)30538-0
DOI:
Reference:
https://doi.org/10.1016/j.apcata.2017.11.016
APCATA 16470
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
27-6-2017
10-11-2017
19-11-2017
Please cite this article as: Rauchdi M, Ali MA, Roucoux A, Denicourt-Nowicki A, Novel
accesstoverbenoneviarutheniumnanoparticles-catalyzedoxidationof␣-pineneinneat
¨
¨
water<Error value=Article Title is Mismatching from Order./>, Applied Catalysis A,
General (2010), https://doi.org/10.1016/j.apcata.2017.11.016
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

Novel access to verbenone via ruthenium nanoparticles-catalyzed
oxidation of -pinene in neat water.
Mariem Rauchdi,a,b Mustapha Ait Ali,b Alain Roucouxa and Audrey Denicourt-
Nowicki*a
a
Ecole Nationale Supérieure de Chimie de Rennes, CNRS, UMR 6226, 11 Allée de Beaulieu,
CS 50837, 35 708 Rennes Cedex 7, France
b
Équipe de Chimie de Coordination et de Catalyse, Département de Chimie, Université Cadi
Ayyad, Faculté des Sciences Semlalia, BP 2390, Marrakech, Morocco
(*) Corresponding author: Audrey.Denicourt@ensc-rennes.fr
Graphical abstract
Research Highlights



Ruthenium nanoparticles proved to be active in pinene oxidation in neat water.
An average yield towards verbenone of 41% was achieved.
Radical species are involved in the allylic oxidation.
1


This catalytic process used eco-respectful reagent (t-BHP) and solvent (H2O).
Abstract
Aqueous suspensions of Ru(0) nanoparticles, stabilized with hydroxyethylammonium salts
and possessing sizes around 2 nm, proved to be active and selective in the mild oxidation of
-pinene in the presence of tert-butylhydroperoxide, in neat water. Verbenone, a product of
great interest for fine chemistry, was obtained as major product with yield up to 41% under
optimized conditions. 2-hydroxy-3-pinanone was identified as a co-product of the reaction, but
with very low amount (< 7%). Kinetic investigations allowed determining the potential reaction
intermediates and by-products. Moreover, mechanistic studies with radical scavengers
confirmed that -pinene oxidation mainly implies both carbon- and oxygen-centered radicals.
Keywords
Ruthenium; Nanoparticles; Allylic oxidation; Terpenic olefins; Water; Sustainable processes
1. Introduction
The allylic oxidation of -pinene 1, a cheap biorenewable constituent of turpentine oil
from pine plants, constitutes a great route for the synthesis of added-value verbenone 2. This
oxygenated compound is used in perfumery, aromatherapy and flavoring industry[1-2], as well
as a key intermediate in the synthesis of therapeutic drugs, such as taxol [3]or potent anti-
ischemic agents [4]. Recently, this enone has been reported to be an acetylcholinesterase
inhibitor, thus presenting potential in early stage treatment of Alzheimer’s disease[5]. Moreover,
2

verbenone is also known as an anti-aggregation hormone, being registered as a biopesticide for
the control of mountain pine beetles [6-7].
Verbenone could be found as a constituent of strawberry (traces detected in Ciflorette)[8], in
vervain (20.5 wt.%)[9], in Rosmarinus officinalis oils (27.0 - 28.9 %)[10] and could also be
obtained from biocatalytic approaches but with limited applications[11-13]. In that context, the
design of selective allylic oxidation processes, using eco-responsible reagents and/or metal
catalysts in non toxic solvents remains of great and challenging interest for improvement of
productivity and selectivity [14]. In fact, during -pinene oxidation, two main competitive
pathways could occur (Scheme 1), leading to the formation of verbenone 2 and verbenol 3
through allylic oxidation or pinene oxide 4 via the epoxidation of the cyclic double bond,
according to the nature of the catalyst and/ or the stability of the radicals formed [15].
- Scheme 1 –
Up to now, various catalytic systems, either molecular complexes [16-20] or heterogeneous
catalysts[21-32], have been used to produce verbenone. Nevertheless, in the most cases, low to
medium yields were obtained (Figure 1) or most of these processes still suffer from various
drawbacks, such as sophisticated catalytic systems, toxic organic solvents and high amounts of
oxidants, long reaction times, and difficult catalyst’s recovery.
- Figure 1 –
In the last decades, metallic nanoparticles have attracted considerable attention as
highly active and eco-responsible catalysts for many processes such as hydrogenation, carbon-
carbon coupling as well as in oxidation reactions[33]. To our knowledge, only few reports are
related to the use of nanoscale catalysts for the oxidation of -pinene. Nanosized Co3O4 particles
proved to be efficient for the epoxidation of this terpenic olefin with air and t-BHP as initiator in
DMF[34], while bimetallic AuCu nanoparticles deposited on TiO2 favored the formation of
3

verbenone with t-BHP in acetonitrile [30]. Finally, in the context of promising technologies
development, the use of cleaner solvents as replacement of usual organic solvents also
contributes to the efforts towards more eco-respectful oxidation processes [35]. For instance,
water has paid great attention, being inexpensive and environmentally benign and affording
unique reactivity and selectivity[36-37].
Herein, we report the use of aqueous suspensions of ruthenium(0) nanoparticles as an
alternative catalyst for the liquid-phase allylic oxidation of -pinene into verbenone, in water as
a suitable industrial green solvent[38]. In this study, ammonium surfactants, well-known in our
team, were used as capping agents of the ruthenium nanospecies, thus providing relevant
micellar nanoreactors for catalytic applications under biphasic liquid-liquid conditions [39-40].
Moreover, N-oxides were evaluated as an alternative and original family of stabilizers,
presenting the advantages to be highly water-soluble and stable under oxidative conditions.
After optimization of the reaction conditions, kinetic and mechanistic investigations have been
performed to identify the various intermediates, as well as the reactive species, in this oxidation
reaction. This novel and eco-compatible process, using nanosized catalytic species in neat water,
could constitute an important technological and environmental breakthrough, for the
valorization of biorenewable resources.
2. Experimental
2.1 Materials and Methods.
Ruthenium(III) trichloride hydrate (RuCl3.3H2O) was obtained from Strem Chemicals. All
commercially available organic compounds, polyvinylpyrrolidinone (PVP; M. W. = 40000) and
the 70% w/w aqueous tert-butylhydroperoxide (Luperox® TBH70X) were purchased from
Aldrich or Acros and used without further purification. Water was distilled twice by
4

conventional method, before use. The ammonium surfactants (HEA16Cl, HEA16Br, HEA16BF4)
were synthesized from already published procedure[40], as well as THEA16Cl [41].
2.2 Synthesis of N-Oxide (NO) derivatives
In a 100 mL round bottom flask equipped with a condenser and a dropping funnel, 2.5 mL (7.5
mmol) dimethylalkylamine were introduced in methanol (10 mL). The reaction mixture was
refluxed for one hour, and 1.15 mL (11.25 mmol, 1.5 eq) of hydrogen peroxide (30 wt. %) was
added dropwise. The reaction was heated at 70°C under vigorous stirring for 15 h, and was
followed by Thin Layer Chromatography. The solvent was removed and the product was dried in
a lyophilizer for 24 h.
1
NO12 (dimethyldodecylamine oxide): White solid, 96% yield, Rf = 0,65 (AcOEt), NMR H (400
MHz, CDCl3, 25°C, TMS):  = 0.81 (t, 3H), 1.19 (m, 16H), 1.27 (m, 2H), 1.79 (m, 2H), 3.14 (s, 6H),
3.20 (m, 2H); NMR 13C (100 MHz, CDCl3, 25°C, TMS):  = 14.09, 22.65, 23.94,26.64, 29.29-
29.56,31.87, 58.30, 71.74, Tf = 120°C.
1
NO16 (dimethylhexadecylamine oxide): White solid, 97% yield, NMR H (400 MHz, CDCl3, 25°C,
TMS):  = 0.81 (t, 3H), 1.19 (m, 24H), 1.27 (m, 2H), 1.79 (m, 2H), 3.13 (s, 6H), 3.20 (m, 2H); NMR
13C (100 MHz, CDCl3, 25°C, TMS):  = 14.10, 22.67, 23,93, 26.64, 29.30-29.67, 31.90, 58.31,
71.72.; Tf = 98°C.
2.3 Synthesis of the aqueous ruthenium (0) suspension
The suspension was prepared at ambient temperature (20°C). The procedure was similar for all
ammonium and N-oxide protective agents.
An aqueous solution of the appropriate surfactant (7.6 x 10-5 mol, 2 eq.) in 4mL of H2O, was
added to 3.6 mg of sodium borohydride (9.5 x 10-5 mol, 2.5 eq) in 2mL H2O. Then this solution
was quickly added under vigorous stirring to an aqueous solution (4 mL) of RuCl3.3H2O
5

precursor (10 mg, 3.8 x 10-5 mol, 1 eq) to obtain 10mL of an aqueous suspension of Ru(0)
nanoparticles. The reduction, characterized by a color change from yellow-brown to black, is
instantaneous and the obtained colloidal suspensions are stable for several weeks.
The aqueous Ru@PVP suspension was synthesized according to the procedure previously
described by Hirai.
2.4 General procedure of allylic oxidation of -pinene and recycling experiments.
In a 100mL round bottom flask sealed with a septum, 5 mL (1.9 x 10-5 mol, 1 eq.) of aqueous
ruthenium (0) suspension was introduced, as well as 258 mg (1.9 x 10-3 mol, 100 eq.) of α-
pinene. Then, the tert-butyl hydroperoxide solution (70%) was added and the reaction mixture
was stirred at ambient temperature (20°C). At the end of the reaction, the product was extracted
with 3 x 3 mL cyclohexane/ ethylacetate (1/1), salted out with NaCl and dried with MgSO4. The
conversion and the selectivity were determined by Gas Chromatography analysis, using octane
as internal standard. The conversion was determined according to the amount of moles of -
pinene consumed over the amount of moles of -pinene introduced in the reactor. The product
yield was calculated according to the amount of moles of product formed over the amount of
moles of substrate introduced in the reactor. The TurnOver Frequency (TOF) value determined
at low conversion, was defined as mol of transformed substrate per mol of introduced Ru per
hour and were determined by kinetic follow-up of the optimized reaction by extraction of small
aliquots of the reaction medium over time. For recycling experiments performed at the end of
the reaction, the product was extracted with 3 x 3 mL cyclohexane/ ethylacetate (1/1). The
aqueous suspension was easily separated by extraction and reused in a new run under similar
reaction conditions.
2.5 Analytical procedures
Transmission Electron Microscopy (TEM) pictures were recorded on a JEOM TEM 100CXII
electron microscope operated at an acceleration voltage of 100 kV. Samples were prepared by
6

placing a drop of the suspension of ruthenium nanoparticles on a carbon-coated grid.
Measurement of the size and number of particles was performed with an automatic counting
program (Image J) using Microsoft Excel to generate histograms of size distribution, on the basis
of 150 measured nanoparticles. Dynamic Light Scattering (DLS) experiments were carried out
using a DelsaNano C instrument (Beckman Coulter) to determine the hydrodynamic size Dh, as
well as the zeta potential of the colloidal suspensions, at room temperature. Gas
chromatography (GC) analyses were run on a Trace GC Ultra (Thermo Scientific) gas
chromatograph, equipped with a GC Restek RTx-5 capillary column (30 m, 0.32 i.d.) with He as
carrier gas. The oven temperature was programmed from 40°c to 250°C at a rate of 10°C/min
with initial and final times of 2 and 5 min, respectively. The injector and detector temperatures
were set at 250°C. The identification of the main oxidation products was performed by
comparison with commercial pure products and the quantification was performed using octane
as internal standard.
3. Results and Discussion
3.1 Influence of the protective agents.
In an initial set of experiments, several protective agents of ruthenium(0) nanoparticles
were screened to define the most suitable micellar nanoreactor (Figure 2) in terms of stability
under the oxidative reaction conditions and catalytic performances. Six easily synthesized
surfactants such as hydroxyethylammonium (HEA) derivatives with various counter-ions (Cl, Br,
BF4)[40], a trishydroxyethyl ammonium (THEA) surfactant [41] and N-oxide (NO12 and NO16)
compounds, were used and compared with the commercially available CTABr surfactant and
PVP (polyvinylpyrrolidinone) polymer. The aqueous suspensions of Ru(0) species were easily
synthesized by chemical reduction of ruthenium chloride (RuCl3.3H2O) with sodium
borohydride, in the presence of the chosen stabilizing agent to avoid aggregation of the
zerovalent nanoparticles. The screening was performed on the liquid-phase oxidation of -
7

pinene in water, at room temperature. The 70% w/w aqueous tert-butylhydroperoxide (t-BHP)
was selected as a suitable oxidant, owing to its higher safety and lower cost than anhydrous
organic t-BHP solutions[42], as well its higher solubility in polar solvents than molecular oxygen
or H2O2[43]. Moreover, from an environmental point of view, this hydroperoxide generates tert-
butanol as by-product, which could be easily recycled[44]. The results are gathered in Figure 2,
based on the -pinene conversion, as well as the verbenone yield
- Figure 2 –
First, as a blank experiment, in the absence of ruthenium nanospecies, no oxidation
products were detected, thus proving an expected catalyzed oxidation reaction. Whatever the
protective agent is, good to complete conversions (from 89 to 100%) were observed. In the HEA
series, the counter-ion (X= Cl, Br, BF4) seems to slightly influence the selectivity towards the
ketone in the following order: Cl > BF4 > Br. In comparison, the reaction proceeds more slowly
with the commercial CTABr surfactant with 89% conversion in the same reaction time (Figure 2,
HEA16Br vs. CTABr). Finally, in the N-oxide series originally reported here as promising
stabilizers, the derivative possessing a C12 lipoliphilic chain proves to be more efficient than
NO16, with quite similar results than HEA16Cl.
Other oxidation products were also formed, but none in yields of 5% or greater, as
frequently reported in the literature[18-19, 22]. 2-hydroxy-3-pinanone 5, which is known as a
chiral auxiliary[45], was identified as the main co-product. Some of these minor products (See
Supplementary Information) were identified by NMR 1H and 13C analyses, and GC-MS
investigations (Scheme 2), such as pinonic acid 6 and pinonic aldehyde 7. Both products have
already been reported in the literature in the oxidation of -pinene using potassium
permanganate[46].
-
Scheme 2 -
3.2 Influence of the HEA16Cl amounts.
8

In a second set of experiments, HEA16Cl was chosen as a relevant protective agent for
the stabilization of Ru(0) nanospecies in neat water and the [HEA16Cl]/Ru ratio was optimized
in the model reaction under standard conditions (3 equiv. t-BHP, 3h, room temperature). The
results are gathered in Figure 3, in terms of conversion, yields of ketone 2 and 2-hydroxy-3-
pinanone 5.
- Figure 3 –
First, with one equivalent of protective agent, the ruthenium nanospecies were less
stable and quickly aggregated under catalytic conditions. Finally, an optimum [HEA16Cl]/[Ru]
ratio of 2 seems to be a good compromise to maintain efficiently the colloidal particles within
the aqueous phase during the catalytic process and allow a relevant activity, combined with a
good selectivity towards the ketone.
3.3 Characterization of Ru0NPs.
Transmission Electron Microscopy (TEM) of the easily prepared Ru@HEA16Cl nanocatalyst
shows well-dispersed and near monodispersed particles with an average diameter of 2.25 nm,
as shown on the size distribution histogram (Figure 4). Around 76 % of particles possess a size
included between 2.0 and 2.5 nm. The Dynamic Light Scattering (DLS) size analysis revealed that
the ruthenium colloids coated with the HEA16Cl surfactant present a hydrodynamic size Dh
around 15 nm. Finally, from zeta potential value, measured by electrophoretic light scattering,
the suspension has an apparent positive charge of + 39 mV, proving the efficient electrosteric
stabilization of the ruthenium(0) particles by HEA16Cl through the combination of the lipophilic
chain (steric protection) and the charged polar head (electrostatic effect).
- Figure 4 –
9

3.4 Optimization of the catalytic reaction
After optimization of the catalyst, the oxidant ratio, as well as the addition technique,
were optimized to achieve pertinent conversions and to limit the formation of co-product, using
ruthenium(0) nanospecies stabilized with 2 equivalents of HEA16Cl (Table 1).
- Table 1 –
First, without t-BHP, no oxidation products were observed (Entry 1). In all other cases
(Entries 2-6), verbenone 2 was identified as major product and 2-hydroxy-3-pinanone 5 as main
co-product. The increase in t-BHP ratio from 1.5 to 3 equivalents (Entries 2-3) leads to a
complete conversion, but with a slightly higher amount of co-product 5. Secondly, the addition of
small amounts of oxidant at regular intervals (1.0 h) was studied, based on a global quantity of 3
equivalents of t-BHP (Entries 4-6). In all cases, the conversion was complete in 3h. However,
through the addition of 2 x 1.5 eq. t-BHP (Entry 4), an optimum verbenone yield of 37 % was
achieved. In other cases (Entries 5-6), the lower amount of the ketone could be attributed to the
formation of higher amounts of by-products, such as the ones resulting from skeletal
rearrangement of -pinene derivatives under the reaction conditions[21, 47]. Hydrogen
peroxide was tested under our conditions for comparison. Unfortunately, as already known in
the literature,[48-50] ruthenium nanospecies catalyzed rapid and non productive
decomposition of H2O2, and the dioxygen released had no major role in the oxidation process.
- Figure 5 –
The kinetics profile (Figure 5) indicates that a complete conversion of the substrate was
achieved in one hour, with a 34% yield in ketone. The TurnOver Frequency (TOF), calculated at
the early stage of the reaction (5 minutes), was around 408 h-1 for the optimized reaction.
Moreover, throughout the reaction, a very low amount of verbenol, which is more reactive
towards oxidation than the -pinene, was observed as a co-product. In fact, under standard
conditions, the verbenol is completely transformed into verbenone in 30 min (Scheme 3), as
already reported in the literature[32].
10

- Scheme 3 –
The formation of 2-hydroxy-3-pinanone 5 (< 7%) could be attributed to the formation of low
amounts of diol 8, followed by its oxidation into compound 5 (Scheme 4). To confirm this
hypothesis, the oxidation of diol 8 with t-BHP (2 x 1.5 eq.), in the presence of Ru@HEA16Cl as
catalyst, leads to a 100% conversion, with a 32% yield in 2-hydroxy-3-pinanone 5. Nevertheless,
at this stage of our investigations, we could not assume that the diol 8 is provided by ring
opening of the epoxide, since the oxidation of the epoxide under optimized conditions did not
lead to 5.
- Scheme 4 –
The oxidation of -pinene has been performed with various temperatures using the
optimized reaction conditions, to study the influence on the catalytic activity and the selectivity
(Table 2, Entries 1-4). Best results in terms of conversion and selectivity were performed at
room temperature (Table 2, Entry 1). In fact, a higher temperature of 60°C (Entry 2) leads to a
decrease in selectivity, potentially due to formation of oligomerization-polymerization products
as already reported in the literature.[18] In contrast, lowering the temperature up to 10° C
(Entry 3) decreases the catalytic activity with 86% conversion in 3h, thus needing higher
reaction time (Entry 4). Moreover, the influence of additional water in the reaction mixture
(Table 2, Entries 5-7) has been studied, since some authors recently reported its promoting
effect on the reaction rate in cyclohexane oxidation.[51] However, no beneficial effect of water
addition has been observed in the oxidation of -pinene under optimized conditions. Moreover,
the addition of a co-solvent, which could improve the solubility of the terpenic olefin, did not
improve the results (Table 2, Entry 8).
- Table 2 –
11

TEM imaging after catalysis revealed that the particles possess an unchanged size,
around 2 nm, with 84 % of the nanoobjects between 1.75 nm and 2.25 nm (Figure 6). Moreover,
the nanospecies could be easily recycled through a biphasic approach, by simple extraction.
They proved to be active in the following run, with a complete conversion and a 37 % yield in
verbenone under similar conditions, thus validating the catalytic lifetime of the ruthenium
particles.
- Figure 6 –
3.5 Mechanistic investigations
In order to demonstrate a probable radical type mechanism, the effects of radical traps
were investigated in the ruthenium(0) nanoparticles catalyzed oxidation of -pinene, using
either oxygen radical scavengers (such as BHT or diphenylamine), as well as carbon radical trap
(such as CBrCl3). First, the introduction after 5 min reaction of butylated hydroxytoluene (BHT),
known as a radical scavenger for peroxy-radicals,[25] leads to a complete inhibition of the
reaction with no more conversion (with a plateau around 33%) and a decrease in the total
ketone/alcohol yields (from 38% to 16% in 1 h), as shown in Figure 7. A similar trend was
observed using diphenylamine, another oxygen radical trap. The use of CBrCl3, a carbon radical
scavenger, leads to a marked inhibition of the products formation, confirming that the
mechanism involved also carbon-centred radicals.
- Figure 7 –
4. Conclusions
12

In conclusion, verbenone, a value-added compound for flavorings industry or
pharmaceuticals production, was synthesized with a 39% yield through the valorization of -
pinene, a biorenewable present in turpentine of pine trees. An eco-compatible allylic oxidation
process was developed using easily prepared aqueous suspensions of ruthenium nanoparticles
as catalyst, in the presence of t-BHP as a safe and quite environment-friendly oxidant and in
water as a suitable safe industrial solvent. Kinetic and mechanistic investigations allowed to
identify some of the intermediates formed, and to prove that radical species are likely to be
involved in the oxidation reaction. This eco-respectful route under mild conditions to verbenone
production may offer a promising alternative to the existing conventional processes.
Acknowledgements
The authors are grateful for the financial support offered by PHC-Toubkal program and Campus
France (PHC Toubkal/15/14: 32462NF). Our thanks are also extended to Patricia Beaunier from
Université Pierre et Marie Curie (Paris) for TEM experiments and Liege Oliviera Biesuz
from Federal University of Rio Grande do Sul (UFRGS) for the synthesis of N-oxide surfactants.
Bibliographic References
[1]
B. Ali, N.A. Al-Wabel, S. Shams, A. Ahamad, S.A. Khan, F. Anwar, Asian Pac. J. Trop.
Biomed. 5 (2015) 601-611.
[2]
[3]
[4]
R. Agrawal, R. Joseph, J. Food Sci. Technol. 37 (2000) 430-432.
P.A. Wender, T.P. Mucciaro, J. Am. Chem. Soc. 114 (1992) 5878-5879.
C. Ju, S. Song, S. Hwang, C. Kim, M. Kim, J. Gu, Y.-K. Oh, K. Lee, J. Kwon, K. Lee, W.-K. Kim, Y.
Choi, Bioorg. Med. Chem. Lett. 23 (2013) 5421-5425.
[5]
[6]
D. Kaufmann, A.K. Dogra, M. Wink, J. Pharm. Pharmacol. 63 (2011) 1368-1371.
C.J. Fettig, S.R. McKelvey, R.R. Borys, C.P. Dabney, S.M. Hamud, L.J. Nelson, S.J. Seybold, J.
Econ. Entomol. 102 (2010) 1846-1858.
[7]
[8]
R.T. Carde, A.K. Minks, Insect Pheromone Research New Directions, Springer, 1997.
R.J. Cannon, D. Agyemang, N.L. Curto, A. Yusuf, M.Z. Chen, A.J. Janczuk, Flavour Frag. J. 30
(2015) 302-319.
[9]
M. Shamsardakani, M. Mosaddegh, A. Shafaati, Iran. J. Pharm.l Res. Volume 2 (2010) 39-
42.
[10] U. Ravid, E. Putievsky, I. Katzir, E. Lewinsohn, N. Dudai, Flavour Frag. J. 12 (1997) 109-
112.
13

[11] K.A.C. Vespermann, B.N. Paulino, M.C.S. Barcelos, M.G. Pessôa, G.M. Pastore, G. Molina,
Appl. Microbiol. Biotechnol. 101 (2017) 1805-1817.
[12] A. Negoi, V.I. Parvulescu, M. Tudorache, Catal. Today (2017).
[13] T. Vanek, J. HalÍK, R. VankovÁ, I. ValterovÁ, Biosci., Biotechnol. Biochem. 69 (2005) 321-
325.
[14] E.F. Murphy, T. Mallat, A. Baiker, Catal. Today 57 (2000) 115-126.
[15] U. Neuenschwander, F. Guignard, I. Hermans, ChemSusChem 3 (2010) 75-84.
[16] M. Islam, D. Hossain, P. Mondal, A.Singha Roy, S. Mondal, M. Mobarak, Bull. Kor. Chem.
Soc. 31 (2010) 3765-3770.
[17] M. Lajunen, A.M.P. Koskinen, Tetrahedron Lett. 35 (1994) 4461-4464.
[18] N.V. Maksimchuk, M.S. Melgunov, Y.A. Chesalov, J. Mrowiec-Białoń, A.B. Jarzębski, O.A.
Kholdeeva, J. Catal. 246 (2007) 241-248.
[19] M. Caovilla, A. Caovilla, S.B.C. Pergher, M.C. Esmelindro, C. Fernandes, C. Dariva, K.
Bernardo-Gusmão, E.G. Oestreicher, O.A.C. Antunes, Catal. Today 133–135 (2008) 695-698.
[20] J. Trissa, P. S. Dhanashree, C.S. Gopinath, S.B. Halligudi, J. Mol. Catal. A 184 (2002) 289-
299.
[21] P.A. Robles-Dutenhefner, B.B.N.S. Brandão, L.F. de Sousa, E.V. Gusevskaya, Appl. Catal. A:
Gen. 399 (2011) 172-178.
[22] O.A. Kholdeeva, I.Y. Skobelev, I.D. Ivanchikova, K.A. Kovalenko, V.P. Fedin, A.B. Sorokin,
Catal. Today 238 (2014) 54-61.
[23] I.Y. Skobelev, K.A. Kovalenko, V.P. Fedin, A.B. Sorokin, O.A. Kholdeeva, Kinet. Catal. 54
(2013) 607-614.
[24] E.P. Romanenko, E.A. Taraban, A.V. Tkachev, Russ. Chem. Bull. 55 (2006) 993-998.
[25] J.-A. Becerra, L.-M. González, A.-L. Villa, J. Mol. Catal. A 423 (2016) 12-21.
[26] P. Selvam, V.M. Ravat, V. Krishna, J. Phys. Chem. C 115 (2011) 1922-1931.
[27] M. Selvaraj, M. Kandaswamy, D.W. Park, C.S. Ha, Catal. Today 158 (2010) 286-295.
[28] N.C. Desai, J.A. Chudasama, B.Y. Patel, K.A. Jadeja, T.J. Karkar, J.P. Mehta, D.R. Godhani,
Microporous and Mesoporous Materials 242 (2017) 245-255.
[29] D.R. Godhani, H.D. Nakum, D.K. Parmar, J.P. Mehta, N.C. Desai, J. Mol. Catal. A 426, Part A
(2017) 223-237.
[30] S. Ajaikumar, J. Ahlkvist, W. Larsson, A. Shchukarev, A.R. Leino, K. Kordas, J.P. Mikkola,
Appl. Catal. A 392 (2011) 11-18.
[31] S.G. Casuscelli, G.A. Eimer, A. Canepa, A.C. Heredia, C.E. Poncio, M.E. Crivello, C.F. Perez, A.
Aguilar, E.R. Herrero, Catal. Today 133–135 (2008) 678-683.
[32] P. Pal, S.K. Pahari, A.K. Giri, S. Pal, H.C. Bajaj, A.B. Panda, J. Mater. Chem. 1 (2013) 10251-
10258.
[33] D. Astruc (Ed.), Nanoparticles and Catalysis, Wiley-VCH Verlag GmbH & Co. KGaA,
Weinheim, 2008.
[34] J. Lei, X.-H. Lu, J.-L. Zhang, X.-L. Wei, D. Zhou, Q.-H. Xia, Indian J. Chem. 52A (2013) 709-
716.
[35] M. Cvjetko Bubalo, S. Vidović, I. Radojčić Redovniković, S. Jokić, J. Chem. Technol.
Biotechnol. 90 (2015) 1631-1639.
[36] E. Genin, V. Michelet, in: Martine Poux, Patrick Cognet, C. Gourdon (Eds.), Green Process
Engineering. From Concepts to Industrial Applications, CRC Press 2015, 2015, pp. 292–324.
[37] M.-O. Simon, C.-J. Li, Chem. Soc. Rev. 41 (2012) 1415-1427.
[38] D. Prat, A. Wells, J. Hayler, H. Sneddon, C.R. McElroy, S. Abou-Shehada, P.J. Dunn, Green
Chem. 18 (2016) 288-296
[39] Audrey Denicourt-Nowicki, A. Roucoux, Chem.l Record 16 (2016) 2127–2141
[40] E. Guyonnet Bile, R. Sassine, A. Denicourt-Nowicki, F. Launay, A. Roucoux, Dalton Trans.
40 (2011) 6524-6531.
[41] C. Hubert, A. Denicourt-Nowicki, J.-P. Guegan, A. Roucoux, Dalton Trans. (2009) 7356-
7358.
[42] E.C. McLaughlin, H. Choi, K. Wang, G. Chiou, M.P. Doyle, J. Org. Chem. 74 (2009) 730-738.
[43] R. Kumar, S. Sithambaram, S.L. Suib, J. Catal. 262 (2009) 304-313.
14

[44] A. Corma, S. Iborra, A. Velty, Chem. Rev. 107 (2007) 2411-2502.
[45] V. Krishnamurthy, J.J. Landi, G.P. Roth, Synth. Commun. 27 (1997) 853-860.
[46] Masruri, M. Farid Rahman, B. Nurkam Ramadhan, IOP Conf. Ser.: Mater. Sci. Eng. 107
(2016).
[47] M.K. Lajunen, T. Maunula, A.M.P. Koskinen, Tetrahedron 56 (2000) 8167-8171.
[48] G. Barak, J. Dakka, Y. Sasson, J. Org. Chem. 53 (1988) 3553-3555.
[49] R. A. Sheldon, I. Arends, U. Hanefeld (Eds.), Green Chemistry and Catalysis, Wiley-VCH
Verlag GmbH & Co. KGaA, Weinheim, 2007.
[50] J.E. Bäckvall (Ed.), Modern Oxidation Methods, Wiley-VCH Verlag GmbH & Co. KGaA,,
Weinheim, 2007.
[51] T.A. Fernandes, C.I.M. Santos, V. André, J. Kłak, M.V. Kirillova, A.M. Kirillov, Inorg. Chem.
55 (2016) 125-135.
15

Figures, schemes and tables captions
Scheme 1. -pinene oxidation: Allylic oxidation vs. Epoxidation
Scheme 2. Identification of some co-products
Scheme 3. Rapid oxidation of verbenol into verbenone
Scheme 4. Plausible pathway for the formation of 2-hydroxy-3-pinanone 5
Figure 1. . An overview of the recent (2005-2017) literature concerning allylic oxidation of -
pinene –Some relevant catalysts.
Figure 2. . Impact of various protective agents in the ruthenium-catalysed oxidation of -pinene
in water. Reaction conditions: Ru nanocatalyst (1.9 x 10-5 mol), -pinene (1.9 x 10-3 mol, 1
equiv.), t-BHP (5.7 x 10-3 mol, 3.0 eq.), H2O (5 mL), ambient temperature (20°C), 3h. Conversion
and verbenone yield (%) were determined by GC analysis using octane as internal standard.
Conversions are mentioned in the green label.
Figure 3. Influence of the HEA16Cl ratio on the stability and the catalytic activity in -pinene
oxidation. Reaction conditions: Ru@HEA16Cl (1.9 x 10-5 mol), -pinene (1.9 x 10-3 mol, 1 equiv.),
t-BHP (5.7 x 10-3 mol, 3.0 eq.), H2O (5 mL), ambient temperature (20°C), 3h. Conversion and
verbenone yield (%) were determined by GC analysis using octane as internal standard.
Conversions are mentioned in the green label.
Figure 4. Transmission Electron Microscopy (Scale Bar = 20nm) and Size Distribution of the
optimized Ru@HEA16Cl catalytic system (150 nanoparticles measured).
Figure 5. Kinetics of Ru@HEA16Cl-catalyzed oxidation of -pinene. Reaction conditions:
Ru@HEA16Cl (1.9 x 10-5 mol), -pinene (1.9 x 10-3 mol, 1 equiv.), t-BHP (5.7 x 10-3 mol, 3.0 eq.),
H2O (5 mL), ambient temperature (20°C), 1h30.
Figure 6. Transmission Electron Microscopy (Scale Bar = 20 nm) and Size Distribution of the
optimized Ru@HEA16Cl suspension after catalytic test (150 nanoparticles measured).
Figure 7. Kinetics of Ru@HEA16Cl-catalyzed oxidation of -pinene after addition of BHT.
Reaction conditions: Ru@HEA16Cl (1.9 x 10-5 mol), -pinene (1.9 x 10-3 mol, 1 equiv.), t-BHP (5.7
x 10-3 mol, 3.0 eq.), H2O (5 mL), ambient temperature (20°C), 1h00
16

Table 1. Optimization of the oxidant ratio and addition on -pinene oxidation with
Ru@HEA16Cl catalyst[a]
Table 2. Influence of the temperature and the dilution on Ru@HEA16Cl- catalysed oxidation of
-pinene[a]
17

Scheme 1.
Figure 1.
Figure 2.
18

Scheme 2.
19

Figure 3.
Figure 4.
Figure 5.
20

Scheme 3.
Scheme 4.
21

Figure 6.
Figure 7.
22

Table 1.
Entry
Oxidant
ratio
Conversion[d] (%)
Verbenone
yield [d] (%)
5 yield [d]
Yield in other
products (%)
(%)
1[a]
2[a]
3[a]
4[b]
5[b]
6[c]
0
0
0
0
2
7
6
3
3
0
1.5
75
34
34
39
29
32
39
59
55
68
65
3.0
100
100
100
100
2 x 1.5
3 x 1.0
6 x 0.5
[a] Reaction conditions: Ru@HEA16Cl (1.9 x 10-5 mol), pinene (1.9 x 10-3 mol, 1 equiv.), t-BHP,
H2O (5 mL), ambient temperature (20°C), 3h. [b] Reaction conditions: Ru@HEA16Cl (1.9 x 10-5
mol), -pinene (1.9 x 10-3 mol, 1 equiv.), t-BHP (3 equiv. in several times), 1 h per t-BHP
addition, H2O (5 mL), ambient temperature (20°C), 3 h global reaction time. [c] Reaction
conditions: Ru@HEA16Cl (1.9 x 10-5 mol), -pinene (1.9 x 10-3 mol, 1 equiv.), t-BHP (3 equiv. in
several times), 30 min per t-BHP addition, H2O (5 mL), ambient temperature (20°C), 3 h global
reaction time. [d] Determined by GC analysis with octane as internal standard.
23

Table 2.
Entry
T (°C)
Additional
H2O (mL)
Conv.[b] (%)
Verbenone
yield [b] (%)
5 yield [b]
Yield in other
products (%)
(%)
1
2
20
60
10
10
20
20
20
20
0
0
100
100
86
39
29
31
33
38
41
39
37
6
3
3
4
4
4
0
4
55
68
52
60
55
51
58
56
3[c]
4[d]
5
0
0
97
2.5
5.0
7.5
0
97
6
96
7
97
8[e]
97
[a] Reaction conditions: Ru@HEA16Cl (1.9 x 10-5 mol), -pinene (1.9 x 10-3 mol, 1 equiv.), t-BHP (5.7 x
10-3 mol, 2 x 1.5 eq.), H2O (5 mL), 3h. [b] Determined by GC analysis with octane as internal standard.
[c] % verbenol formed. [d] After 5h reaction. [e] 1 mL CH3CN
24