Efficient Liquid-Assisted Grinding Selective Aqueous Oxidation of Sulfides Using Supported Heteropolyacid Catalysts

Article abstract of DOI:10.1002/cctc.201900296

The present work reports the preparation of 40MoAl200 and its full characterization using a number of analytical techniques (XRD, TEM, TGA, BET, EDX). Liquid-assisted ball milling proved to be a key tool to achieve both the best efficiency of 40MoAl200 as a novel Keggin type catalyst in the selective sulfoxidation reaction and also for succeeding in its effective recovery and reuse. In addition, the liquid assisted grinding process was studied in detail evaluating the influence of different parameters such as frequency of rotation (rpm), number and size of the stainless steel balls used and reaction time. The use of aqueous hydrogen peroxide is essential as water proved to exert a crucial role to improve both yields and selectivity towards sulfoxide formation. The procedure was representatively extended to a number of substrates with the possibility to extend the scope of the system to produce sulfoxides in high yields (up to 95 %) and satisfactory selectivities (up to 80 %). The catalyst proved to be recoverable and reusable under the optimized reaction conditions.

Full text of DOI:10.1002/cctc.201900296

Accepted Article
Title: Efficient liquid-assisted grinding selective aqueous oxidation of
sulfides using supported heteropolyacid catalysts
Authors: Valeria trombettoni, Ana Franco, A. Gabriel Sathicq,
Christophe Len, Gustavo P. Romanelli, Luigi Vaccaro, and
Rafael Luque
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To be cited as: ChemCatChem 10.1002/cctc.201900296
Link to VoR: http://dx.doi.org/10.1002/cctc.201900296
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10.1002/cctc.201900296
ChemCatChem
Efficient liquid-assisted grinding selective aqueous oxidation of sulfides using
supported heteropolyacid catalysts
Valeria Trombettoni a,b, Ana Francoa, A. Gabriel Sathicqc, Christophe Lend, Gustavo P.
Romanellic, Luigi Vaccaro b* and Rafael Luque a,e*
a Departamento de Química Orgánica, Universidad de Córdoba, Edificio Marie Curie (C-3),
Carretera Nacional IV-A, Km 396, E14014, Córdoba, Andalucía, Spain, E-mail:
rafael.luque@uco.es
b 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
c Centro de Investigación y Desarrollo en Ciencias Aplicadas “Dr. Jorge J. Ronco” (CINDECA),
CCT-La Plata-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Universidad
Nacional de La Plata, 47◦N 257, B1900AJK La Plata, Argentina
d IRCP, UMR 8247 CNRS Chimie ParisTech11, rue Pierre et Marie Curie, F-75005 Paris, France
e Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya str., 117198,
Moscow, Russia
KEYWORDS: Mechanochemistry; Oxidation; Heteropolyacids
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ABSTRACT
The present work reports the preparation of 40MoAl200 and its full characterization using a
number of analytical techniques (XRD, TEM, TGA, BET, EDX). Liquid-assisted ball milling
proved to be a key tool to achieve both the best efficiency of 40MoAl200 as a novel Keggin type
catalyst in the selective sulfoxidation reaction and also for succeeding in its effective recovery and
reuse. In addition, the liquid assisted grinding process was studied in detail evaluating the influence
of different parameters such as frequency of rotation (rpm), number and size of the stainless steel
balls used and reaction time. The use of aqueous hydrogen peroxide is essential as water proved
to exert a crucial role to improve both yields and selectivity towards sulfoxide formation. The
procedure was representatively extended to a number of substrates with the possibility to extend
the scope of the system to produce sulfoxides in high yields (up to 95%) and satisfactory
selectivities (up to 80%). The catalyst proved to be recoverable and reusable under the optimized
reaction conditions.
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INTRODUCTION
Mechanochemical processes have been classified by IUPAC as a “chemical reaction induced by
1
the direct adsorption of mechanical energy”. The term includes several technologies in which
mechanical energy can be generated and transferred to the reactants to trigger a reactive process.
In particular the ball milling exploits the mechanical energy generated by the movements of the
milling balls; the size, number and material of milling balls employed are the most important
parameters that influence this phenomenon.2 Different options of ball milling movements are
possible; thus shaking, mixing, vibrational or planetary movements could drastically influence the
outcome of a mechanochemical transformation. One of the most relevant advantages of ball
milling (“dry milling”) is the possibility to work in a solventless system; under effective milling
which ensures optimum contacts between solid reagents, facilitating solvent-free reactions.3–4
Another strategy commonly put in place deals with the utilization of small amounts of solvents, to
conduct “Liquid Assisted Grinding” (“LAG”); indeed in the presence of minimum quantities of
reaction medium, solvent effects can be brought to the mechanochemical reaction also improving
the contact among reagents. 5 Due to the properties mentioned above, ball milling is considered an
engaging tool especially in a sustainable context; indeed has remarkably attracted the attention in
6
research in recent decades. Mechanochemistry is to date widely exploited in a wide range of
7
applications in different fields including down-stream processing for plants treatment,
8
mechanical pre-treatment of lignocellulosic biomass,
and pharmaceutical formulation
9
preparation. Additionally, mechanochemistry has been recently extended to the synthesis of
metal complexes, 10 the production of catalysts and nanomaterials 11-15 and the formation of metal-
organic frameworks. 16 Organic mechanochemical synthesis has also been gaining momentum in
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recent years considered an important and versatile tool for the sustainable production of target
organic compounds. 17-22
23-25
Additionally, LAG has proven to be useful for a variety of transformations
many advantages of this tool compared to conventional (heating) technologies
how yields of the isolated products can be improved dramatically. 28
confirming the
26-27
and showing
Despite mechanochemical oxidation reactions could potentially be regarded as unpredictably safe
due to the shock-sensitive nature of many oxidants, recent research in the field has been focused
on the employment of safer, easier-to-handle materials. Indeed several mechanochemical
oxidation protocols are widely reported in literature in which shock-stable oxidants were
employed, thus ensuring safety under mechanochemical conditions. 29-33
In particular, this contribution is focused on sulfoxidation reaction, an important process generally
focused on the selective production of alkyl, benzyl, and aryl sulfoxide compounds useful for
several applications in different fields as active pharmaceutical ingredients (APIs), 34-35 ligands, 36
37
and flavour agents. In this context, sulfoxidation reactions using mechanochemical activation
have been little explored in literature. A representative example has been reported by Cravotto et
al. for the desulfurization of medium/high sulfur content paraffins (up to 3000 mg/kg). The
procedure was carried using Oxone® as oxidant and sulfone derivatives were selectively produced
in high yields (99%) and with no trace of sulfoxide detected. 38 In the oxidation reaction of organic
sulfurs, catalysts play an important role and therefore the careful tailoring of catalytic systems is
crucial to achieve chemoselectivity and avoid the formation of side-products. Heterogeneous
catalysts are usually preferred in order to simplify the isolation procedures and minimize waste
associated to the synthetic protocol. Several methodologies have been reported in sulfoxidation
reactions using a wide range of heterogeneous catalysts. Representative examples include
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39
transition metal functionalized graphene oxide,
Keplerate polyoxometalates ionic liquid
complexes, 40 iron oxides on carbon-based supports, 41 transition-metal oxide clusters, 42 tungsten
43
44
(VI) organic complexes
and carbon supported polyoxometalates.
Among the different
employed catalysts, heteropolyacids (HPA) are useful in oxidation reactions 45 due to their strong
Brønsted acidity and redox properties. HPAs are polyoxometalate inorganic cages known also as
Keggin type materials that possess the general formula Hn(MX12O40)n, wherein M is the central
atom and X is the heteroatom attached; typically M is P or Si and X is W or Mo. The disadvantages
of the use of HPA related to their solubility in organic solvent commonly used and their low surface
area (< 4 m2/g). For this reason, the development of supported HPAs is an important issue which
has been extensively investigated in recent years40, 45-49 to design advanced heterogeneous catalysts
with improved surface areas (even if with low porosity). This contribution has been aimed to
explore the mechanochemical LAG sulfoxidation using designed heterogeneous HPA catalysts
prepared via wet impregnation of phosphomolybdic acid on CATAPAL 200, a commercial
crystalline pseudoboehmite as compared to bulk HPAs. The use of boehmite as catalytic support
is well reported in literature; it could be considered good support thanks to its high reactivity to
the surface; indeed its surface is covered by many hydroxyl groups which make possible an easy
functionalization. Moreover it possesses several advantages including low toxicity, remarkably
50-55
thermal and mechanical stability and good adsorption capacity.
Herein, we report the
structural features of such structure and its application in the mechanochemical LAG sulfoxidation
of several organic sulfides as a representative synthetic organic application of heterogeneous
catalysts under mechanochemical conditions. Hydrogen peroxide in water has been employed as
ecofriendly, sustainable and cheap oxidant. 39
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EXPERIMENTAL SECTION
The reactions were carried out in a planetary ball milling Retsch-PM-100 using a 25 mL stainless
steel jar. All reagents were commercially obtained and used without further purification, unless
otherwise specified. Diphenyl sulfide (assay 98%), methyl phenyl sulfide (assay ≥ 99%)
thioanisole (assay ≥ 99%), dibenzyl sulfide (assay ≥ 95%), 4-4’ diamine diphenyl sulfide (assay
98%), 4 nitro-4’ amine diphenyl sulfide ( assay >99%), hydrogen peroxide solution (30% w/w in
H2O), urea peroxide solution (assay 97%), tert-butyl hydrogen peroxide solution 8 5-0/6.0 M in
decane) and phosphomolybdic acid hydrate (≥ 99.99%, traces metals basis) were purchase from
Sigma Aldrich. CATAPAL200® (particle size ~ 60 µm) was provided by Sasol Chemicals (USA)
LLC. The reactions were monitored by GC and GC-MS, using an Agilent 6890N GC model
equipped with a Supelco 2-8047-U (60m x 25m x 25µm i.d.) capillary column and an FID detector
and the products were confirmed using GC (7890A)-MS (5975D inert MSD with Triple-Axis
Detector) Agilent equipped with a capillary column HP-5MS (60 m x 0.32 mm), at the Research
Support Service Center (SCAI) from University of Cordoba.
Catalysts characterization
XRD patterns were recorded using a Bruker D8 DISCOVER A25 diffractometer with a slit of
0.018° from 2θ=10° to 80° and counting time of 5 s per step using CuKα radiation. Textural
properties of the samples were determined by N2 physisorption using a Micromeritics ASAP 2000
automated system with the Brunauer-Emmet-Teller (BET) and the Barret-Joyner-Halenda (BJH)
methods. The samples were outgassed for 24 h at 130°C under vacuum (P0 = 10−2 Pa) and then
analyzed. TEM images were recorded with JEOL 1200, at the Research Support Service Center
(SCAI) from Universidad de Cordoba. Samples were suspended in ethanol and deposited straight
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away on a copper grid prior to analysis. EDX analysis were performed in a JEOL-SEM JSM-6610
LV scanning microscope in backscattered electron mode at 3/15 kV fitted with elemental analysis.
ICP-MS analysis were conducted in a Philips PU 70000 sequential spectrometer equipped with an
Echelle monochromator (0.0075 nm resolution). Samples were digested in HF: HNO3: HCl (1:1:1)
and subsequently analyzed at the SCAI of Universidad de Cordoba. TGA measurements were
performed using a System Setaram Setsys 12 TGA instrument. Samples were heated at a heating
rate of 10 ºC min-1, in Nitrogen (50 mL min-1) at the temperature range 30-800 ºC. Pyridine (PY)
and 2,6-dimethylpyridine (DMPY) titration experiments were carried out at 300 °C, via gas phase
adsorption of the basic probe molecules applying a pulse chromatographic titration methodology.
The catalyst used (≈0.025 g) was fixed inside a tubular stainless steel microreactor (4 mm internal
diameter) by Pyrex glass wool. A cyclohexane solution of titrant (0.989 M in PY and 0.686 M in
DMPY, respectively) was injected into a gas chromatograph through a microreactor in which the
catalyst was previously sited. The injected base was analyzed by gas chromatography with a flame
ionization detector and using an analytical column of 0.5 m length, containing 5 wt % of
polyphenylether in the Chromosorb AW-DMCS in 80/100. The quantity of probe molecule
adsorbed by the solid acid catalyst can subsequently be easily quantified. In order to distinguish
between Lewis and Brønsted acidity, it was assumed that all DMPY selectively titrates Brønsted
sites (methyl groups hinder coordination of nitrogen atoms with Lewis acid sites) while PY titrates
both Brønsted and Lewis acid sites in the materials. Thus, the difference between the amounts of
PY (total acidity) and DMPY (Brønsted acidity) adsorbed should correspond to Lewis acidity in
the materials.
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Preparation of 10,20,30,40 MoAl200
Four different HPA supported catalysts having different content of phosphomolybdic acid were
prepared via wet impregnation method over CATAPAL 200. The procedure for the preparation of
40MoAl200 was performed in a round bottomed-flask equipped with a magnetic stirrer where 1 g
of phosphomolybdic acid hydrate was dissolved in 50 mL of acetone and 2.5 g of CATAPAL 200
were slowly added. The mixture was stirred at r.t. for 10 min, followed by solvent removal by
rotary evaporator. The synthesized catalyst was dried overnight at r.t. An identical procedure was
employed for the synthesis of all catalysts with the only difference in the amount of
phosphomolybdic acid hydrate used; 0.25, 0.5, 0.75 g for the synthesis of 10MoAl200,
20MoAl200, 30MoAl200 respectively.
Representative mechanochemical procedure for the oxidation reactions of diphenyl sulfide
(1a) using 40MoAl200 as catalyst: In a typical procedure 1 mmol of diphenyl sulfide (1a)
(169 µL), 1 mmol of H2O2 30% (w/w) water solution (113 µL) and 0.043 mmol% of catalyst (2
mg) were laid in a 25 mL jar and eight (Ø 10 mm) stainless steel balls were employed. The
planetary ball milling was carried on at 350 rpm for 15 min. The crude reaction mixture was
recovered from the jar using 200 µL of toluene and the liquid phase was analyzed by GC and GC-
MS using the following conditions; injector temperature 250°C, detector temperature 350°C. Gas
carrier: nitrogen (1.8 mL/min), temperature program: from 120°C (4 min) to 200°C at 10°C/min.
The retention times of diphenyl sulfide (1a), diphenyl sulfoxide (2a), and diphenyl sulfone (3a)
were 8.244, 10.326, 10.659 min., respectively.
Mechanochemical procedure for synthesis of diphenyl sulfoxide (2a); Scaled up reaction: For
the scale up of the protocol 20 mmol of diphenyl sulfide (1a) (3.3 mL), 20 mmol of H2O2 30%
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(w/w) water solution (2.25 mL) and 0.043 mmol% of catalyst (40 mg) were laid in a 25 mL jar
and eight (Ø 10 mm) stainless steel balls were employed. The planetary ball milling was carried
on at 350 rpm for 15 min. The crude reaction mixture was recovered from the jar using 3.5 mL of
Toluene. The liquid phase was dried using sodium sulfate and subsequently purified by
crystallization in water methanol solution (8 mL, 3:2 water methanol). Diphenyl sulfoxide was
obtained as a white solid (19.2 mmol, 3.88 g, 96% isolated yield). The product structure was further
confirmed using GC-MS and NMR.
RESULTS AND DISCUSSION
Different catalysts containing varying HPA loadings were prepared by impregnating
44
phosphomolybdic acid into CATAPAL200 obtaining 10MoAl200, 20MoAl200, 30MoAl200
and 40MoAl200. The commercial support employed for this purpose (CATAPAl200) is a
crystalline boehmite material exhibiting well defined features in term of surface area, pore
diameter, acidity and thermal resistance as illustrated in the detailed materials characterization.
XRD studies
Diffraction XRD patterns are shown in Figure 1. The black solid line pattern corresponds to
CATAPAL200 boehmite crystalline orthorhombic phase exhibiting all the characteristic peaks. 48
The impregnation of phosphomolybdic acid on CATAPAL200, illustrated for 40MoAl200 did not
significantly influence the crystalline structure of the support (discontinuous red line, Figure 1).
The orthorhombic structure was well retained. The crystal size of 40MoAl200 was estimated as
31.98 nm using the Scherrer equation based on the characteristic 2θ diffraction line at 28.173.
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40MoAl200
CATAPAL200
20
40
60
80
2
Figure 1. XRD patterns; Black solid line: CATAPAL200; Discontinuous red line: 40MoAl200.
Catalyst morphology from TEM images
TEM studies were performed to confirm XRD analyses. The images obtained from three different
regions of 40MoAl200 were compared with those of the boehmite support. No morphological or
structural changes could be visualized between support and impregnated material (40MoAl200 vs
CATAPAL200). The boehmite phase was preserved upon impregnation, in good agreement with
XRD data (Figure 2).
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Figure 2. TEM analysis of 40MoAl200 (left panel) and TEM analysis of CATAPAL200 (right
panel).
Energy dispersive x-ray spectroscopy (EDX)
EDX analysis were additionally carried on in order to demonstrate the presence of
phosphomolybdic acid in the impregnated CATAPAL200 materials. Table 1 summarizes the
molar percentage of all elements detected and reported as average values of three analyses on
different regions of the materials. EDX analysis confirms the homogeneous presence of
molybdenum and phosphorus in 40MoAl200 (Figure 3b and 3c). This information was further
confirmed by ICP-MS quantitative analysis in which 26.10 ppm of Mo was detected in the
material.
Table 1. EDX analysis results.
Entry Material
CATAPAL
Element Intensity %Atom %Weight
a
a
Al
O
0.87
1.20
0.85
0.70
0.72
0.96
30.0
70.0
26.5
68.0
5.0
42.0
58.0
31.0
47.4
21.1
0.4
1
200
Al
O
2
40MoAl200
Mo
P
0.5
a Average of data obtained from the analyses of three different regions of the catalysts.
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Figure 3. SEM image of 40MoAl200, b: EDS mapping of Mo, c: EDS mapping of P, d: EDS
mapping of Al.
Porosimetry analysis
Figures 4a, and 4b depict the adsorption isotherm of CATAPAL200 and 40MoAl200, respectively.
Type III isotherms (IUPAC classification) could be observed for both support and impregnated
40MoAl200, with a typical profile of non-porous materials (Figure 4). Indeed, the values for the
Brunauer–Emmett–Teller (BET) (Table 2, entries 1 and 2) surface area and pore volumes only
account for interparticular macroporosity. After HPA impregnation, a decrease of surface area was
observed (from 65 to 48 m2/g). This reduction may be attributed to the observed homogeneous
dispersion of HPA within the interparticular voids.
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Figure 4. N2 sorption isotherms of (a) CATAPAL200, (b) 40MoAl200.
Table 2. Textural properties of the materials prepared.
Entry
1
Material
SBET (m2 g-1) a DBJM
(nm)b
VBJH (cm3 g-1) c
CATAPAL200
40MoAl200
65
48
-
-
0.46
0.38
2
a
SBET: specific surface area was calculated by the Brunauer-Emmett-Teller (BET)
b
equation. DBJH: mean pore size diameter was calculated by the Barret-Joyner-
Halenda (BJH) equation. c VBJH: pore volumes were calculated by the Barret-Joyner-
Halenda (BJH) equation.
Thermogravimetry analysis (TGA)
In order to evaluate the thermal stability of 40MoAl200, TGA analyses were performed. Figures
5a and b show TGA diagrams of CATAPAL200 and 40MoA200, respectively. Both of them
feature three key mass losses (black lines). In the first one (from 0 to 100 °C) a slight weight
decrease can be observed due the loss of physisorbed water. A 15% mass loss could be measured
in the 400 °C to 500 °C range, in which a clear phase transition (sharp exothermic peak at ca.
520ºC) is typical from the formation a gamma-alumina phase via boehmite de (stable phase from
ca. 450ºC); followed by a stable weight from 600-800°C. 53 Figure 5b depicts the TGA profile of
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40MoAl200, for which a 5% of weight loss was observed from 200 °C to 400 °C, attributed to the
release of water from the keggin clusters. This phenomenon is typical for Keggin type catalysts. 44
The significant mass loss (-15%) observed in the 400-500 °C similarly accounts for the observed
phase transition.
5
5
0
-5
0
-5
0
0
-5
-5
-10
-15
-20
-25
-30
-35
-10
-15
-20
-25
-30
-35
-10
-15
-20
-10
-15
-20
b
a
200
400
600
800
200
400
600
800
Temperature (°C)
Temperature (°C)
Figure 5. Thermal analysis of a: CATAPAL200, b: 40MoAl200.
Acidity of materials
The determination of the amount of acid sites and their nature (Brønsted or Lewis) was evaluated
via pyridine titration. Table 3 summarizes values for both the support and the impregnated HPA
materials in which a clear increase in total acidity (both Brönsted and Lewis) can be observed,
confirming successful incorporation of the Keggin clusters.
Table 3. Acidity of the new materials measured by pyridine/dimethyl pyridine adsorption method.
Entry Material
Total acidity
(µmol PY/g)
Brønsted acidity Lewis
acidity
(µmol DMPY/g) (µmol PY/g)
1
2
CATAPAL200
40MoAl200
10
89
10
53
-
36
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Catalytic activity experiments
The investigation on the catalytic efficiency of synthesized MoAl200 catalysts (see Experimental
section) was initially performed in the model oxidation of diphenyl sulfide (1a) to optimize the
reaction conditions. Subsequently, the mechanochemical reaction was extended to a range of
organic sulfides in order to define an efficient, versatile and sustainable LAG protocol (Scheme 1).
Scheme 1. General LAG protocol for the sulfoxidation of diphenyl sulfide (1a).
Table 4 summarizes the main results for the mechanochemical reaction for the different
synthesized catalytic systems under optimized conditions. Blank runs (performed in the absence
of any catalyst) gave only 8% of conversion after 15 min, confirming the essential role of the
catalyst in the sulfoxidation reaction. The same result was observed when the reaction was
performed in the presence of the support CATAPAL200 (Table 4, Entry 10). As it could be
observed from Table 4, 40MoAl200 proved to be the best catalytic system, providing excellent
results in term of conversion (95%) and selectivity (80%) towards diphenyl sulfoxide (2a) (Entry
2). 20MoAl200 and 10MoAl200 were less efficient allowing less than 15% conversion to 2a and
a higher selectivity towards the formation of diphenyl sulfone (3a) (Table 4, entries 4, 6).
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Table 4. Catalytic studies of HPA supported materials in the mechanochemical oxidation of
diphenyl sulphide
Selectivity
Catalyst (mol%)
-
Entry
Conversion (%)a
(2a)/(3a)b
1
2
8
7:3
8:2
40MoAl200
(0.043)
95
30MoAl200
(0.043)
3
4
80
10
15
5
8.5:1.5
3:7
20MoAl200
(0.043)
20MoAl200
(0.430)
5
3:7
10MoAl200
(0.043)
6
0:10
10MoAl200
(0.430)
7
5
0:10
40MoAl200
(0.043)
8c
5
8.5: 0.5
40MoAl200
(0.043)
9d
40
8:2
7:3
7.5
10
CATAPAL200
b
aMonitored by GC analysis; Determined by GC-MS analyses. Reaction conditions: 25 stainless steel mL jar
containing 8 balls (Ø 10 mm),(1a)/ H2O2 1:1 molar ratio, 350 rpm, 15 min c 1mmol of urea-hydrogen peroxide
employed as oxidant d 1mmol of hydrogen tert-butoxide employed as oxidant
Increasing the amounts of 20MoAl200 or 10MoAl200 did not show any improvement both in
terms of conversion and selectivity (Table 4, entries 5, 7), for which these materials-together with
30MoAl200 were not further employed in any additional catalytic studies. Due to the data above
reported, the catalytic activity of 40MoAl200 was further optimized under ball milling conditions.
Firstly, different oxidant agents were tested; aqueous hydrogen peroxide proved to be more
efficient than urea hydrogen-peroxide and tert-butyl hydroperoxide as observed in Entries 8-9,
Table 4 (see also Graph S1). The effect of catalyst loading was subsequently tested; with no
relevant effect observed changing the amount of catalyst in the range of 0.043-0.172 mol% (Table
5, Entries 2-4) using 0.5 mmol H2O2. A slightly higher conversion to diphenyl sulfone (3a) was
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obtained employing 2 mmol of oxidant (Entry 10-12). A slight decrease of conversion was
observed, with no influence on the selectivity using just 1 equivalent of H2O2 at increased catalyst
amounts (Entries 6-8). This can be ascribed to an insufficient contact between reagents using the
minimum amount of water present in LAG (113 µL). To confirm this effect, the same reaction was
performed adding 160 μL of water (0.025 M) and a >99% conversion was achieved with 83% of
selectivity towards diphenyl sulfoxide (2a) (Table S2, entry 2). The increased amount of water
improved reaction yields as it allows a better contact among the reagents suggesting that this
protocol falls in the liquid assisted grinding (LAG) definition.
Table 5. Effect of the amount of catalyst in the mechanochemical oxidation of diphenyl sulfide
Entry
H2O2 (equivs)
40MoAl200
(mol%)
Conversion
(%)a
Selectivity
(2a)/(3a)b
1
2
/
/
/
9.3:0.7
9:1
0.043
0.086
0.172
/
50
58
60
8
0.5
3
4
8.8:1.2
7:3
5
6
0.043
0.086
0.172
/
95
50
65
15
>99
75
>99
8:2
1
7
8:2
8
7:3
9
4.5:5.5
3:7
10
11
12
0.043
0.086
0.172
2
4:6
2:8
b
aMonitored by GC analyses; Determined by GC-MS analyses. Reaction conditions: 25 stainless steel mL jar
containing 8 balls (Ø 10 mm), 350 rpm, 15 min
Additional details on the influence of the amount of oxidant over time are reported in Table S1.
We also evaluated the role of the medium used both on catalytic efficiency and selectivity. Water
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confirmed to give much better results compared to other solvents with varying polarity such as
methanol or hexane (see Table S2, Graph S2, SI).
The effect of the milling speed in the ball mill was subsequently considered starting from
previously found best conditions (25 mL stainless steel jar containing 8 balls (Ø 10 mm), (1)/ H2O2
1:1, 0.043 mol% 40MoAl200, 350 rpm, 15 min) for which diphenyl sulfoxide (2a) was obtained
in high conversion (95%) and selectivity (80%). Figure 6 clearly depicts a lower conversion
obtained when the milling speed was reduced from 350 to 150 rpm, with no relevant change in
selectivity (Table S3).
Figure 6. Effect of the milling speed in the mechanochemically LAG assisted oxidation.
Reaction conditions: 25 mL stainless steel jar containing 8 balls (Ø 10 mm), (1a)/H2O2 1:1.
Another critical parameter in ball-milling experiments is the number of balls used. The
experiments reported above were performed with 8 milling balls having a diameter Ø of 10 mm.
The influence of this important parameter was investigated varying the number from 2 to 8 balls
in the same reaction conditions. We concluded that increasing the number of balls from 2 to 8
conversion increased from 56% to 95%) in line with the increase of the internal energy system.
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The selectivity to diphenyl sulfoxide (2a) can be improved using only 2 balls but conversion were
lower even after prolonged reaction times (see Table S5 for more details).
Optimization scale-up and substrate scope
A representative scaled-up reaction of the optimised sulfoxidation of diphenyl sulfide (1a) was
subsequently performed. The reaction was carried out using 20 mmol of diphenyl sulfide (1a) with
a constant number and size of milled balls (8 balls, Ø 10 mm). Better results in terms of conversion
and selectivity (100%, 9.95:0.05: 2a/3a) were achieved as compared to smaller 1 mmol scale
reactions. The satisfactory data obtained, confirmed the potential of mechanochemical reactions
for large-scale applications. The isolation procedure was further optimized (see experimental
section) to allow facile catalyst recovery (40MoAl200) and a 96% isolated yield of the pure
product 2a upon simple recrystallization.
Additionally, the scope of the proposed LAG mechanochemical protocol was further extended to
a variety of organic sulfides 1b-e (Scheme 2). The best conditions and results for each compound
were individually optimized and the most relevant results have been summarized in Table 6.
Methyl phenyl sulfide (1c) (Table 6, entries 3-4) proved to be very reactive, affording the
preparation of the corresponding sulfoxide (2c) in 10 min at 99% conversion, 97% isolated yield
(Table 6, entry 4). In this case, 150 rpm stirring was sufficient to provide a quantitative yield of
methyl phenyl sulfoxide (2c) (Table 6, entry 4,). Thioanisole (1b) (Table 6, entry 1,2) proved to
be less reactive, with a larger amount of oxidant (0.5 mmol), energy (200 rpm) and time (20 min)
required to obtain (methylsulphinyl)benzene (2d) with satisfactory results (97% of conversion,
88% of selectivity).
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Scheme 2. “LAG” procedures to obtain organic sulfoxides 2b-e.
Table 6. Mechanochemical oxidation of various sulphides using 40MoAl200 as catalyst
Entry
1
(1b-e)/
H2O2 molar
ratio
rpm
200
t (min)
20
C (%)a
>99
Selectivity
Sulfide
2b-e/3b-eb
1
7:3
2
3
0.5
0.5
350
350
15
15
97
8.8:1.2
4.5:5.5
>99
4
5
6
7
8
0.25
150
200
200
350
350
10
15
15
20
20
>99
98
9.95:0.05
9.9:0.1
5:5
1
2
1
2
>99
10
9.8:0.2
5:5
55
aMonitored by GC analysis; b Determined by GC-MS analyses. Reaction conditions: 25 stainless
steel mL jar, 0.043 %mol 40MoAl200
Benzyl sulfide (1d) (Table 6, entries 5 and 6) exhibited similar reactivity as compared to diphenyl
sulfide (1a); less than 1 mmol of oxidant was not enough to obtain good results in terms of
conversion and selectivity. However, (sulfinylbis(methylene))dibenzene (2c) could be obtained in
high conversion ( >99%) performing the reaction at 200 rpm for 20 minutes (Table 6, entry 6).
The sulfoxidation of 4-amino-4’-nitrodiphenyl sulfide (1d) (Table 6, Entries 7, 8) was significantly
more challenging, with only 55% conversion to 4-amino-4’-nitrodiphenyl sulfoxide (2c) was
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10.1002/cctc.201900296
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detected. The reaction was less selective (ca. 50% selectivity to target product) and bis(4-
nitrophenyl)sulfane was observed as reaction side-product by GC-MS. These results indicate that
the oxidation of the amino group into the corresponding nitro group competed with the sulfide to
sulfoxide oxidation (Supporting Information). Only traces of 4-amino-4’- nitrodiphenyl sulfone
(3d) were found. The results obtained confirmed that the electronic nature of organic sulfides can
indeed influence the LAG mechanochemical reaction in term of conversion and selectivity, 37 with
electron-rich sulfides being more reactive than the electron-deficient compounds.
Catalyst stability and reusability experiments
The recovery and reuse of 40MoAl200 was investigated under optimum conditions using the
model reaction/substrates 1a. Upon reaction completion, the product was extracted from the
catalyst 40MoAl200 by adding a minimum amount of organic solvent under ball milling (150 rpm,
5 min) toward optimum dissolution. Afterwards, the liquid phase taken from the reactor was then
evaporated under reduced pressure to furnish the pure product 2a in 96% isolated yield (Table 7,
entry 1). The chamber of the ball mill containing the catalyst 40MoAl200 was then oven-dried
(100°C, 10 min) and the solid catalyst recovered as a fine powder and reused in further runs. TGA
analysis of the recovered catalyst was performed (200 °C, 2 h, air) showing no significant loss of
weight (see Figure S2). The reused catalyst 40MoAl200 exhibited a stable and comparable
efficiency to the fresh catalyst over three consecutive runs. After the three reuse cycles, 40
MoAl200 was recovered and its structure was further characterized by XRD, TEM, BET analyses
in order to study the influence of the mechanical and chemical stress after subsequent reactions on
the catalyst features.
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Table 7. Recovery and reuse experiments of 40MoAl200 in the mechanochemical oxidation of
diphenyl sulfide
Entry
Run
Conversion
(%)a
Selectivity
Yield (%mol)
(2a)/(3a)b
1
2
I
99
99
95
9.95:0.05
9.95:0.05
9.5:0.5
96
95
92
II
3
III
b
a Monitored by GC analyses;
Determined by GC-MS analyses. Reaction conditions: 25 stainless steel mL jar
containing 8 balls (Ø 10 mm), 0.043 %mol 40MoAl200, (1a)/ H2O2 1:1 molar ratio, 350 rpm, 15 min.
The characterization analyses have been included as part of the Supporting Information, clearly
demonstrating that the recovered catalyst maintained its crystallinity, particle size (31.25 nm by
Scherrer equation based on characteristic 2θ 28.173) and morphology (Figures S3, S4). Textural
properties did not show any relevant changes as compared to the fresh catalyst (Figure S5,
Table S6) EDX, ICP and the acidity analyses (see Table S7-8) additionally confirmed the stability
of the catalyst during the repeated reaction runs and no relevant leaching of phosphomolybdic acid
was observed. Furthermore the mapping of 40MoAl200 (Figure S7) confirmed the retention of the
homogeneous dispersion of HPA over CATAPAL200.
CONCLUSIONS
In conclusion, we have reported a detailed study on the preparation and use of 40MoAl200 as
heterogeneous catalyst under Liquid assisted grinding (LAG) conditions for the selective oxidation
of organic sulfides to sulfoxides. The catalyst was proved to be highly efficient, showing excellent
results in terms of conversions and selectivity. Several parameters including the influence of the
mechanochemical energy milling speed, number of milling balls and time were investigated and
confirmed to be crucial parameters for the application of this technology in the use of
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10.1002/cctc.201900296
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heterogeneous catalysts. Most importantly, the protocol could be scaled up 20 times (from 1 mmol
to 20 mmol scale reagents) to achieve quantitative conversion and selectivity (both >99%) to
products with the possibility of product isolation (isolated product yields in the 90-97% range).
Several sulfide substrates were tested and successfully oxidized under LAG mechanochemical
conditions, demonstrating the versatility of the developed protocol. The reusability of the catalyst
was also successfully accomplished, confirming that the mechanochemical approach does not
influence the crystallinity, surface and/or textural properties of the catalyst under the investigated
optimum reaction conditions. The LAG protocol developed could be considered efficient,
versatile, sustainable and suitable for preparative applications, with the potential to be scaled up
for the synthesis of relevant organic compounds (i.e. pharmaceutical intermediates).
ACKNOWLEDGMENTS
The Università degli Studi di Perugia and MIUR are acknowledged for financial support to the
project AMIS, through the program “Dipartimenti di Eccellenza - 2018-2022”. GPR and AGS
thanks for the financial support of CONICET through the “Becas Externas“ program and UNLP.
RL gratefully acknowledges support from MINECO under project CTQ2016-78289-P, co-
financed with FEDER funds. The publication has been prepared with support from RUDN
University Program 5-100.
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