Metal-free mechanochemical oxidations in Ertalyte jars

Article abstract of DOI:10.3762/bjoc.15.172

The authors acknowledge Form-Tech Scientific for the loan of the FTS-1000 Shaker Mill apparatus (Form-Tech Scientific, Canada, https://formtechscientific.com/). Authors are grateful to MIUR (Italy, PRIN project: multifunctional polymer composites based on grown materials). A. P. is grateful to MIUR for “Finanziamento delle Attività Base di Ricerca (FABR 2017)“.

Full text of DOI:10.3762/bjoc.15.172

Metal-free mechanochemical oxidations in Ertalyte® jars
Andrea Porcheddu*1, Francesco Delogu2, Lidia De Luca3, Claudia Fattuoni1
and Evelina Colacino*4
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 1786–1794.
1Dipartimento di Scienze Chimiche e Geologiche, Università degli
Studi di Cagliari, Cittadella Universitaria, SS 554 bivio per Sestu,
09042 Monserrato (Ca), Italy, 2Dipartimento di Ingegneria Meccanica,
Chimica e dei Materiali, Università degli Studi di Cagliari, via Marengo
2, 09123 Cagliari, Italy, 3Dipartimento di Chimica e Farmacia,
Università degli Studi di Sassari, via Vienna 2, 07100-Sassari, Italy
and 4Université de Montpellier & Institut Charles Gerhardt de
Montpellier (ICGM), UMR 5253 CNRS – UM – ENSCM, 8 Rue de
l’Ecole Normale, 34296 Montpellier, Cedex 5, France
doi:10.3762/bjoc.15.172
Received: 07 April 2019
Accepted: 05 July 2019
Published: 25 July 2019
This article is part of the thematic issue "Mechanochemistry II".
Guest Editor: J. G. Hernández
Email:
© 2019 Porcheddu et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Andrea Porcheddu* - porcheddu@unica.it; Evelina Colacino* -
evelina.colacino@umontpellier.fr
* Corresponding author
Keywords:
AZADO; Ertalyte®; green chemistry; mechanochemistry;
NaOCl·5H2O; selective oxidation; TEMPO
Abstract
Aimed at eliminating or at least significantly reducing the use of solvents, sodium hypochlorite pentahydrate crystals
(NaOCl·5H2O) in the presence of a catalytic amount of a nitrosyl radical (TEMPO or AZADO) have been successfully used to in-
duce mechanochemical oxidative processes on several structurally different primary and secondary alcohols. The proposed redox
process is safe, inexpensive and performing effectively, especially on the macroscale. Herein, an Ertalyte® jar has been successful-
ly used, for the first time, in a mechanochemical process.
Introduction
The conversion of primary and secondary alcohols to the corre- discovery of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl, common-
sponding carbonyl compounds (aldehydes and ketones, respec- ly known as TEMPO by Lebedev and Kazarnowskii in 1960
tively) is of such importance in organic chemistry that it finds has been hailed as a significant breakthrough in the field of
very few parallels in other synthetic organic processes [1,2]. redox reactions, allowing the fast and selective oxidation of
These transformations can be achieved by using a wide range of alcohols to the related carbonyl compounds under very mild
oxidizing reagents [3], but most of them are difficult-to-handle conditions [6,7]. Initially used in a stoichiometric amount [8],
and suffer from waste problems due to large amounts of by- over the last 20 years it has been exploited successfully in cata-
products, thus decreasing the atom efficiency [4,5]. The lytic quantities in combination with other oxidants [9]. A
1786

Beilstein J. Org. Chem. 2019, 15, 1786–1794.
diverse range of co-oxidant agents (N-chlorosuccinimide, sponding aldehydes/ketones based on a mechanochemical acti-
NaOCl, Oxone®, PhIO, PhICl2, PhI(OAc)2, I2, CAN, etc.) has vation [28]. In comparison to solution-based techniques, ball-
been intensively investigated with varying results in terms of milling procedures provide an ideal solution for overcoming
yields, chemical selectivity, and environmental sustainability many of the drawbacks described above, due to the simplicity
[10-18]. All oxidation procedures have their advantages and of use, shorter reaction times, large-scale production, low cost
their flaws, so the search for efficient, selective, high-yielding, and sustainability of this methodology [28-39]. In addition,
environmentally benign methods and atom-economical pro- impact forces, that are generated by ball-milling media involve
cesses continues to be a pivotal challenge for chemists [19]. a very minimal fraction of reactive material mimicking the ideal
Stahl and many other researchers worked in this direction behavior/trend of highly diluted reactive systems. This peculiar
achieving noteworthy results by using air/oxygen as an aspect of mechanochemical reactions, especially in redox pro-
oxidizing agent in the presence of a suitable metal complex [20- cesses conducted in no-metal reactors, could prevent excessive
25]. However, even these recent methods suffer from serious heating of the jar, avoid the decomposition of starting materials
drawbacks, such as the use of precious metals often combined and therefore, limit the formation of byproducts [40]. Following
with sophisticated organic ligands, which makes them expen- our interest in mechanochemistry and the design of new cost-
sive, especially if implemented on an industrial scale. In addi- effective oxidation procedures, we have tried to combine both
tion, increasingly restrictive legislation against residual metals topics to the best [41-49]. In particular, we were mainly inter-
in manufactured goods and active ingredients stimulates the ested in developing a general, selective and versatile alcohol-to-
ongoing search for new metal-free solutions to the problem aldehyde/ketone oxidative protocol applied to primary and sec-
making this challenge even topical [26,27]. Based on the ondary alcohols by using an oxidizing agent as cheap and eco-
considerations mentioned above, we focused on an alternative friendly as possible.
strategy to activate the oxidation process. In particular, in this
study, we used sodium hypochlorite pentahydrate In order to optimize all the experimental conditions, we fine-
(NaOCl·5H2O) in the presence of a catalytic amount of a tuned the reaction by using 3-phenyl-1-propanol as a model
nitrosyl radical (TEMPO or AZADO) to induce mechanochem- reagent and N-chlorosuccinimide (NCS) as an oxidizing agent.
ical oxidation reactions on suitably selected primary and sec- NCS is one of the most widely used co-oxidizing reagents in
ondary alcohols. Performed in a high-energy ball mill and with homogeneous-phase TEMPO-assisted oxidation reactions and,
the unprecedented utilization of Ertalyte® jars, the mechanical we have gained valuable experience in handling this reagent in
activation allows obtaining the oxidized products from a broad several mechanochemical applications [45,46].
spectrum of initial substrates. We show that the proposed
mechanochemical method is definitely safe, performing effec- N-Chlorosuccinimide (1.1 mmol) and 3-pheny-1-propanol
tively and inexpensive, thus providing an interesting synthetic (1.0 mmol) were milled together in the presence of TEMPO
route that can be scaled up to pilot and industrial levels.
(5 mol %), K2CO3 (4.0 mmol) and KBr (3.0 mol %) for
10 minutes in a zirconia jar containing 5 balls (5 mm Ø) of the
same material (Scheme 1).
Results and Discussion
Since the most commonly employed oxidizing agents are solid
reagents, we decided to develop an efficient and eco-friendly For all the experiments, we never observed a complete conver-
process for the selective oxidation of alcohols to the corre- sion of the alcohol into the aldehyde. Moreover, the first experi-
Scheme 1: Oxidation of 3-pheny-1-propanol (1a) with N-chlorosuccinimide (NCS) in the presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO)
under mechanical activation conditions [50]. aPercentages of conversion were calculated by GC–MS using an internal reference standard.
1787

Beilstein J. Org. Chem. 2019, 15, 1786–1794.
mental results showed the key role of the base in the conver- after ten minutes. Any attempt to improve this conversion by
sion of an alcohol into an aldehyde: it fails in the absence of varying other parameters such as the number (up to 15 balls,
K2CO3, reaches a maximum of 51% with 4 equivalents and 5 mm Ø) and the diameter of balls (from 3 up to 10 mm Ø), or
decreases (27%) for higher amounts (Scheme 1). This is mainly using a different base (KHCO3 or Na2CO3) turned out to be un-
due to the fact that the concentration of the active oxidizing successful.
agent, HOCl is strongly dependent on the amount and strength
of the base used in the grinding mixture [51].
The use of other solid oxidants such as trichloroisocyanuric acid
(TCCA) did not bring any advantage to the process (Scheme 3),
Two different mechanisms have been postulated for similar and the aldehyde was only detected in negligible amounts
reactions in homogeneous phase: one occurs under acidic (GC–MS analyses). The (diacethoxyiodo)benzene acid (PIDA)
conditions, while the other works better in a basic medium allowed to further improve the alcohol-to-aldehyde conversion
through a cyclic dipolar mechanism (Scheme 2) [52,53]. On the by a few percentage points (57%), but the formation of 2 equiv-
contrary, under ball-milling conditions, it is possible to hypoth- alents of acetic acid makes it unsuitable for a mechanochemical
esize that only the cyclic dipolar mechanism, which operates process [55]. Also, Oxone® and NH2CONH2·H2O2 appeared to
mostly in basic conditions, allowed to gain access to the desired fail in the oxidation of 3-phenyl-1-propanol (1a) to the corre-
aldehyde.
sponding aldehyde.
Interestingly, the formation of a significant amount of over-oxi- Subsequently, we turned our attention to sodium hypochlorite
dation [54] and elimination byproducts was observed for (NaOCl), an inexpensive and widely used oxidizing reagent
3-pheny-1-propanol (1a) when increasing the reaction time (up also applied as a disinfectant and household bleaching agent,
to 20 min, Scheme 1). In contrast, comparable results were ob- usually sold as a 3–6% solution in water. Commercially avail-
tained when the milling time was reduced to 3 minutes, leading able NaOCl is highly basic (pH ≈ 12.7) that dramatically slows
to an alcohol/aldehyde ratio very similar to that one obtained down the oxidation process, and NaHCO3 has to be added to
Scheme 2: Hypothesized pathways for the TEMPO-assisted oxidation of alcohols in a) basic or b) acidic reaction conditions.
Scheme 3: TEMPO-assisted oxidation of 3-pheny-1-propanol (1a) under mechanical activation conditions. aPercentages of conversion were calcu-
lated by GC–MS using an internal reference standard.
1788

Beilstein J. Org. Chem. 2019, 15, 1786–1794.
both maximize the concentration of the active oxidizing agent and sufficiently stable and safe for potential applications in
HOCl, and to absorb bleach [56]. The addition of a catalytic mechanochemistry (Figure S1a, Supporting Information File 1)
amount of KBr promotes the in situ generation of HOBr, which [64-67].
is a stronger oxidant than HOCl [57].
Once the most promising oxidant was identified, NaOCl·5H2O
The results improved remarkably by using as oxidant a 6% (1.1 mmol), 3-phenyl-1-propanol (1.0 mmol), NaHCO3
aqueous solution of NaOCl (1.14 mL, 1.1 mmol) adsorbed on (2.2 mmol), and KBr (3 mol %) were milled together in the
NaHCO3 (6.5 g) in the presence of a catalytic amount of presence of TEMPO (5 mol %) for 20 minutes in a zirconia jar
TEMPO (5.0 mol %) and KBr (3.0 mol %) (Table 1, entry 6). containing 6 balls (5 mm Ø) of the same material. NaHCO3
Within 20 minutes, the alcohol was completely and selectively plays the double role of base and adsorbent for liquid alcohols
oxidized into the corresponding aldehyde (as assessed by (Table 2, entry 1). The first results were promising and showed
GC–MS analyses). The use of NaCl, alone or in combination a good alcohol-to-aldehyde conversion (75%). We have also
with NaHCO3, as an adsorbent [58] (Table 1, entries 1–5, 7) or used a Teflon jar, but we observed lower conversions (<50%).
bases (Na2CO3, Table 1, entries 7 and 8) other than NaHCO3 In addition, the reproducibility of data was often poor. In our
significantly reduces the alcohol-to-aldehyde conversions.
ongoing efforts to develop mechanochemical reactions in jars
manufactured from thermoplastic materials as alternatives to
Based on these preliminary results, we decided to replace Teflon, having high mechanical resistance, rigidity, and hard-
aqueous NaOCl (bleach) with Ca(OCl)2 that has been reported ness, we were pleased to find that Ertalyte® displayed an excel-
previously as a valid alternative to NaOCl aqueous solutions for lent performance in the mechanical process. All other parame-
mechanochemical chlorination reactions of hydantoins [41,59]. ters being equal, the conversion efficiency improved signifi-
However, also using this oxidant, we observed low conversions cantly by switching to an Ertalyte® jar (86%) [68] which could
(31%) and the formation of significant amounts of byproducts, be further enhanced (93%) by slightly increasing the amount of
mainly halides and olefins (elimination byproducts). The use of the oxidant agent (1.5 equiv). Ertalyte® jars (Figure S1b, in
liquid-assisted grinding (LAG) procedures [60-62] by adding Supporting Information File 1) are composed of polyethylene
small quantities of water (250 μL) improved the performance of terephthalate (PET-P) and characterized by wear- and abrasion-,
the reaction (alcohol-to-aldehyde conversion: 41%), but also chemical and moderate acid resistance, with a low coefficient of
raised the percentage of elimination products (38%). Solid friction and FDA approved [69].
NaOCl·5H2O, which has been discovered over a century ago,
represented a turning point in our search for a suitable reagent, In the absence of TEMPO, the oxidation reaction did not work
avoiding some of the previously described shortcomings. As of anymore, while in the absence of KBr, the conversion rate was
2013, this reagent is commercially available [63], inexpensive considerably reduced. The use of bases other than NaHCO3
Table 1: Oxidation of 3-phenyl-1-propanol (1a) with aqueous NaOCl (6%, bleach) under mechanical activation conditions [50].
Entry
Base
NaCl (g)a
Time (min)
Aldehyde (%)b
Byproducts (%)b
1
2
3
4
5
6
7
8
NaHCO3 (2.0 g)
NaHCO3 (2.0 g)
NaHCO3 (1.0 g)
NaHCO3 (1.0 g)
NaHCO3 (2.5 g)
NaHCO3 (6.5 g)
Na2CO3 (2.0 g)
Na2CO3 (6.0 g)
3.5
3.0
5.0
5.0
2.5
–
15
15
15
30
15
22
22
22
73
77
78
78
88
>99
61
55
16
22
8
6
4
–
37
41
3
–
aNaCl was used as an adsorbent [58] in combination with NaHCO3 or Na2CO3. bPercentages of conversion were calculated by GC using an internal
reference standard.
1789

Beilstein J. Org. Chem. 2019, 15, 1786–1794.
Table 2: Oxidation of 3-phenyl-1-propanol (1a) with NaOCl·5H2O crystals under mechanical activation conditions using ZrO2 or Ertalyte® jars. Optimi-
zation of the reaction conditions.
Entry
NaOCl·5H2O (mmol)
Jar
Aldehyde (%)a
Alcohol (%)a
Byproducts (%)a
1
2b
3
4
5c
1.1
1.1
1.1
1.5
1.5
Zirconia
Zirconia
Ertalyte®
Ertalyte®
Ertalyte®
75
70
86
93
69
19
11
9
5
27
6
19
5
2
4
aPercentages of conversion were calculated by GC using an internal reference standard. bThe reaction time was extended to 40 min. cThe amount of
TEMPO was decreased from 5 to 3 mol %.
(Na2CO3 or sodium citrate) resulted in low alcohol-to-aldehyde Aliphatic alcohols 1a–5a with carbon chains of different length
conversions (<40%) and promoted, conversely, the formation of were oxidized to give the corresponding aldehydes 1b–5b in
significant amounts of olefins (>25%) resulting from halide good yields and no carboxylic acid derivatives were observed in
elimination. Any attempt to lower the amount of the nitrosyl any sample. Similar results were obtained for alcohols contain-
catalyst resulted in a poor conversion (69%, Table 2, entry 5). ing an aliphatic carbon ring in their backbone, such as cyclo-
Once the reaction conditions were fine-tuned, this procedure hexylmethanol (5a). Interestingly, the oxidation reaction of
was applied to a range of alcohols to assess the scope of the benzylic alcohols proceeded smoothly to completeness in about
reaction. The results are shown in Scheme 4.
10 minutes even without need for TEMPO.
Scheme 4: Scope of primary alcohol oxidation under mechanical activation conditions. aAll yields refer to isolated pure products. bThe compound was
prepared according to the general procedure A (see Supporting Information File 1) without adding TEMPO catalyst, and the reaction was completed
within ten minutes.
1790

Beilstein J. Org. Chem. 2019, 15, 1786–1794.
The results changed significantly with benzylic alcohols deco- (10 mol %), as well as longer reaction times (up to 1.5 h), did
rated with an electron-withdrawing group in the aromatic ring not lead to any significant improvement. However, we were
such as 4-nitrobenzylalcohol (and 4-cyanobenzylalcohol), pleased to find that the less hindered 2-aza-adamantane-N-oxyl
which required 5 mol % of TEMPO to be oxidized.
(AZADO) was more effective than TEMPO in terms of conver-
sion and yield with the model alcohol substrate, promoting an
Based on these experimental results, we hypothesize that the almost quantitative conversion of 4-phenyl-2-butanol into
reaction proceeded by a mechanism different from the classical benzylacetone in only 30 min (Scheme 6, ketone 11b). This
solution-based TEMPO-assisted oxidation of alcohols, as illus- protocol was successfully extended to other secondary alcohols
trated in Scheme 5 [65]. In the first step of the reaction, potas- to afford the corresponding ketones 11b–19b in high conver-
sium bromide, used as a co-catalyst, generates in situ sodium sions and yields.
hypobromite, a more favorable oxidizing reagent than sodium
hypochlorite. Ion metathesis due to the presence of KCl may The oxidation of sterically hindered secondary alcohols such as
lead to KOBr (Scheme 5, reaction 1). Subsequently, the species adamantan-2-ol (Scheme 4, alcohol 16a) required doubling of
MOBr (M = Na, K) reacts with water to form HOBr, which is the quantity of the nitrosyl catalyst (AZADO, 2 mol %) and
the active oxidizing agent (Scheme 5, reaction 2). Once the longer reaction times (from 30 to 60 min) to achieve comple-
oxidizing agent formed, it reacts with the benzylic alcohols 6a tion. Another useful feature of this protocol can be seen in the
or 7a to afford the corresponding intermediate benzyl hypo- case of secondary benzyl alcohols, where the oxidation reac-
bromites 6c or 7c (Scheme 5, reaction 3). In the final step, the tion to the corresponding ketones proceeded smoothly even
base deprotonates the acidic benzylic proton leading to the cor- without the necessity to use the nitrosyl catalyst (Scheme 6, ke-
responding benzaldehyde 6b or 7b (Scheme 5, reaction 4).
tones 17b–19b). With all benzylic alcohols examined, the
GC–MS analyses showed that the reactions were nearly com-
The oxidation of furfuryl alcohol gave furfural (10b), but in low plete in about 15 minutes, ketones 17b–19b being isolated in
and irreproducible yields together with significant amounts of high yields and purities. Finally, we investigated if this protocol
byproducts. As expected, the reaction with conjugated alcohols could be potentially implemented on a larger scale. Pleasingly,
(cinnamic alcohol, propargyl alcohol, etc.) was less successful we were able to scale-up the oxidation of 1a and 11a from a
due to the competing chlorination of the multiple bonds. 1 mmol up to a 10 mmol scale without any significant drop in
Prompted by these findings, we further explored the efficacy of terms of purity and yield, thus confirming the method’s poten-
the protocol with a variety of secondary alcohols. Unfortu- tial adaptability to industrial settings.
nately, the oxidation reaction tested on 4-phenyl-2-butanol
proceeded with low conversion yields (45%). An increase in The proposed mechanism for the TEMPO-based oxidative
both the amount of the oxidant (2 equiv) and the nitrosyl radical conversion of primary and secondary alcohols to the corre-
Scheme 5: Proposed mechanism for the oxidation of benzylic alcohols 6a and 7a under mechanochemical conditions and in the presence of KBr.
1791

Beilstein J. Org. Chem. 2019, 15, 1786–1794.
Scheme 6: Scope of secondary alcohols in the oxidation under mechanical activation conditions. aAll yields refer to isolated pure products. b2-Aza-
adamantane-N-oxyl (AZADO, 2 mol %), 60 min. cOxidation carried out without AZADO catalyst, 15 min. The title compound was prepared according
to the general procedure B (see Supporting Information File 1).
sponding carbonyl compounds is described in Scheme 7 and oxidizing species. Subsequently, a catalytic amount of −OBr
shares similarities with that postulated in other previous studies oxidizes the TEMPO radical to the N-oxo-ammonium ion A.
in solution.
The latter in turn rapidly oxidizes the alcohol to the correspond-
ing carbonyl compound and gives the reduced form of TEMPO,
the hydroxylamine C, TEMPOH. Then hydroxylamine C is
reoxidized by −OBr regenerating the starting TEMPO radical or
directly the N-oxo-ammonium species A, thus closing the cata-
lytic cycle (Scheme 7).
Conclusion
The conversion of primary and secondary alcohols to alde-
hydes and ketones, respectively, is one of the most important
reactions in the panorama of organic chemistry. Although the
literature describes a plethora of reagents and methodologies,
most of them use toxic/harmful reagents that often cause serious
environmental and public health concerns. Crystalline sodium
hypochlorite (NaOCl·5H2O) in the presence of a catalytic
amount of a nitrosyl radical allowed developing a redox process
without using any metal catalyst. With the aim to eliminate or at
least reduce the use of solvents, NaOCl·5H2O, among all the
oxidants tested, was the one that best fitted with a general
mechanochemical oxidative process of alcohols in Ertalyte®
jars. The latter material never has been explored before in any
of the mechanochemical transformations described in the litera-
Scheme 7: Possible mechanism for the TEMPO-mediated oxidation of
primary and secondary alcohols by using NaOCl·5H2O and catalytic
KBr.
In general, NaOCl works as a co-oxidant agent, and in the cata- ture and produced outperforming results compared to those ob-
lytic cycle reacts with KBr generating in situ −OBr, a stronger tained in zirconium oxide jars.
1792

Beilstein J. Org. Chem. 2019, 15, 1786–1794.
14.Jing, Y.; Daniliuc, C. G.; Studer, A. Org. Lett. 2014, 16, 4932–4935.
doi:10.1021/ol5024568
15.Li, X.-Q.; Zhang, C. Synthesis 2009, 1163–1169.
doi:10.1055/s-0028-1087850
Supporting Information
Supporting Information File 1
Experimental procedures, characterization of new
compounds and copies of 1H and 13C NMR spectra.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-172-S1.pdf]
16.Miller, R. A.; Hoerrner, R. S. Org. Lett. 2003, 5, 285–287.
doi:10.1021/ol0272444
17.Sahoo, P. K.; Bose, A.; Mal, P. Eur. J. Org. Chem. 2015, 6994–6998.
doi:10.1002/ejoc.201501039
18.Dabral, S.; Hernández, J. G.; Kamer, P. C. J.; Bolm, C.
ChemSusChem 2017, 10, 2707–2713. doi:10.1002/cssc.201700703
19.Parmeggiani, C.; Cardona, F. Green Chem. 2012, 14, 547–564.
doi:10.1039/c2gc16344f
20.Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C.
Chem. Rev. 2013, 113, 6234–6458. doi:10.1021/cr300527g
21.Cao, Q.; Dornan, L. M.; Rogan, L.; Hughes, N. L.; Muldoon, M. J.
Chem. Commun. 2014, 50, 4524–4543. doi:10.1039/c3cc47081d
22.Hoover, J. M.; Ryland, B. L.; Stahl, S. S. J. Am. Chem. Soc. 2013, 135,
2357–2367. doi:10.1021/ja3117203
Acknowledgements
The authors acknowledge Form-Tech Scientific for the loan of
the FTS-1000 Shaker Mill® apparatus (Form-Tech Scientific,
Canada, https://formtechscientific.com/). Authors are grateful to
MIUR (Italy, PRIN project: multifunctional polymer compos-
ites based on grown materials). A. P. is grateful to MIUR for
“Finanziamento delle Attività Base di Ricerca (FABR 2017)“.
23.Ochen, A.; Whitten, R.; Aylott, H. E.; Ruffell, K.; Williams, G. D.;
Slater, F.; Roberts, A.; Evans, P.; Steves, J. E.; Sanganee, M. J.
Organometallics 2019, 38, 176–184.
ORCID® iDs
doi:10.1021/acs.organomet.8b00546
Andrea Porcheddu - https://orcid.org/0000-0001-7367-1102
Claudia Fattuoni - https://orcid.org/0000-0002-6956-7967
Evelina Colacino - https://orcid.org/0000-0002-1179-4913
24.Stahl, S. S.; Alsters, P. L., Eds. Liquid Phase Aerobic Oxidation
Catalysis: Industrial Applications and Academic Perspectives;
Wiley-VCH Verlag GmbH: Weinheim, Germany, 2016.
doi:10.1002/9783527690121
25.Wang, L.; Shang, S.; Li, G.; Ren, L.; Lv, Y.; Gao, S. J. Org. Chem.
2016, 81, 2189–2193. doi:10.1021/acs.joc.6b00009
26.https://www.fda.gov/cosmetics/guidanceregulation/lawsregulations/ucm
127406.htm (accessed June 16, 2019).
27.https://www.fda.gov/downloads/Drugs/Guidances/UCM509432.pdf
(accessed June 16, 2019).
References
1. Dubrovskiy, A. V.; Kesharwani, T.; Markina, N. A.; Pletnev, A. A.;
Raminelli, C.; Yao, T.; Zeni, G.; Zhang, L.; Zhang, X.; Rozhkov, R.;
Larock, R. C., Eds. Comprehensive Organic Transformations: A Guide
to Functional Group Preparations, 3rd ed.; John Wiley and Sons: New
York, U.S.A., 2018.
28.Cravotto, G.; Calcio Gaudino, E. Oxidation and Reduction by Solid
Oxidants and Reducing Agents using Ball-Milling. In Ball Milling
Towards Green Synthesis: Applications, Projects, Challenges;
Ranu, B. C.; Stolle, A., Eds.; Royal Society of Chemistry: Cambridge,
UK, 2015; pp 58–80. doi:10.1039/9781782621980-00058
29.Andersen, J.; Mack, J. Green Chem. 2018, 20, 1435–1443.
doi:10.1039/c7gc03797j
30.Bolm, C.; Hernández, J. G. Angew. Chem., Int. Ed. 2019, 58,
3285–3299. doi:10.1002/anie.201810902
31.Do, J.-L.; Friščić, T. ACS Cent. Sci. 2017, 3, 13–19.
doi:10.1021/acscentsci.6b00277
2. Smith, B. M. March's Advanced Organic Chemistry: Reactions,
Mechanisms, and Structure, 7th ed.; John Wiley & Sons: New York,
U.S.A., 2013.
3. Zhang, Z.; Gao, J.; Xia, J.-J.; Wang, G.-W. Org. Biomol. Chem. 2005,
3, 1617–1619. doi:10.1039/b502662h
4. Burke, S. D.; Danheiser, R. L. Oxidizing and Reducing Agents; John
Willey & Sons: Chichester, UK, 1999.
5. Tojo, G.; Fernández, M. Oxidation of Alcohol to Aldehyde and Ketones;
Springer: New York, U.S.A., 2006. doi:10.1007/b135954
6. Lebedev, O. A.; Kazarnovskii, S. N. T. Khim. Tekhnol., Gorky 1959, 8,
649.
32.Užarević, K.; Ferdelji, N.; Mrla, T.; Julien, P. A.; Halasz, B.; Friščić, T.;
Halasz, I. Chem. Sci. 2018, 9, 2525–2532. doi:10.1039/c7sc05312f
33.Margetić, D.; Štrukil, V. Practical Considerations in Mechanochemical
Organic Synthesis; Mechanochemical Organic Synthesis; Elsevier:
Amsterdam, Netherlands, 2016; pp 1–54.
doi:10.1016/b978-0-12-802184-2.00001-7
34.Michalchuk, A. A. L.; Tumanov, I. A.; Boldyreva, E. V. CrystEngComm
2019, 21, 2174–2179. doi:10.1039/c8ce02109k
35.Piras, C. C.; Fernández-Prieto, S.; De Borggraeve, W. M.
Nanoscale Adv. 2019, 1, 937–947. doi:10.1039/c8na00238j
36.Tan, D.; García, F. Chem. Soc. Rev. 2019, 48, 2274–2292.
doi:10.1039/c7cs00813a
37.Tan, D.; Loots, L.; Friščić, T. Chem. Commun. 2016, 52, 7760–7781.
doi:10.1039/c6cc02015a
7. Lebedev, O. L.; Kazarnovskii, S. N. T. Zh. Obshch. Khim. 1960, 30,
1631–1635.
8. Merbouh, N.; Bobbitt, J. M.; Brückner, C. J. Org. Chem. 2004, 69,
5116–5119. doi:10.1021/jo049461j
9. Beejapur, H. A.; Zhang, Q.; Hu, K.; Zhu, L.; Wang, J.; Ye, Z.
ACS Catal. 2019, 9, 2777–2830. doi:10.1021/acscatal.8b05001
and references cited therein.
10.Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem. 1987, 52,
2559–2562. doi:10.1021/jo00388a038
11.Bolm, C.; Magnus, A. S.; Hildebrand, J. P. Org. Lett. 2000, 2,
1173–1175. doi:10.1021/ol005792g
12.Dabral, S.; Wotruba, H.; Hernández, J. G.; Bolm, C.
ACS Sustainable Chem. Eng. 2018, 6, 3242–3254.
doi:10.1021/acssuschemeng.7b03418
38.Mack, J.; Fulmer, D.; Stofel, S.; Santos, N. Green Chem. 2007, 9,
1041–1043. doi:10.1039/b706167f
13.Einhorn, J.; Einhorn, C.; Ratajczak, F.; Pierre, J.-L. J. Org. Chem.
1996, 61, 7452–7454. doi:10.1021/jo9609790
1793

Beilstein J. Org. Chem. 2019, 15, 1786–1794.
39.Li, A. Y.; Segalla, A.; Li, C.-J.; Moores, A.
63.Sodium hypochlorite pentahydrate (NaOCl·5H2O, S0939) is
commercially available from TCI chemicals.
ACS Sustainable Chem. Eng. 2017, 5, 11752–11760.
doi:10.1021/acssuschemeng.7b03298
40.Andersen, J.; Brunemann, J.; Mack, J. React. Chem. Eng. 2019, 4,
1229–1236. doi:10.1039/c9re00027e
https://www.tcichemicals.com/eshop/en/it/catalog/list/search?searchWo
rd=S0939&client=default_frontend&output=xml_no_dtd&proxystyleshe
et=default_frontend&sort=date%3AD%3AL%3Ad1&oe=UTF-8&ie=UTF
-8&ud=1&exclude_apps=1&site=en_it&mode=0 (accessed June 15,
2019).
41.Colacino, E.; Porcheddu, A.; Charnay, C.; Delogu, F.
React. Chem. Eng. 2019, 4, 1179–1188. doi:10.1039/c9re00069k
42.Colacino, E.; Carta, M.; Pia, G.; Porcheddu, A.; Ricci, P. C.; Delogu, F.
ACS Omega 2018, 3, 9196–9209. doi:10.1021/acsomega.8b01431
43.Colacino, E.; Porcheddu, A.; Halasz, I.; Charnay, C.; Delogu, F.;
Guerra, R.; Fullenwarth, J. Green Chem. 2018, 20, 2973–2977.
doi:10.1039/c8gc01345d
44.Porcheddu, A.; Delogu, F.; De Luca, L.; Colacino, E.
ACS Sustainable Chem. Eng. 2019, 7, 12044–12051.
doi:10.1021/acssuschemeng.sc2019007099
64.Hirashita, T.; Sugihara, Y.; Ishikawa, S.; Naito, Y.; Matsukawa, Y.;
Araki, S. Synlett 2018, 29, 2404–2407. doi:10.1055/s-0037-1609629
65.Okada, T.; Asawa, T.; Sugiyama, Y.; Iwai, T.; Kirihara, M.; Kimura, Y.
Tetrahedron 2016, 72, 2818–2827. doi:10.1016/j.tet.2016.03.064
66.Okada, T.; Asawa, T.; Sugiyama, Y.; Kirihara, M.; Iwai, T.; Kimura, Y.
Synlett 2014, 25, 596–598. doi:10.1055/s-0033-1340483
67.Watanabe, A.; Miyamoto, K.; Okada, T.; Asawa, T.; Uchiyama, M.
J. Org. Chem. 2018, 83, 14262–14268. doi:10.1021/acs.joc.8b02541
68.For more technical details about the Ertalyte®, see the following web
site (Mitsubishi Chemical Advanced Materials):
45.De Luca, L.; Giacomelli, G.; Porcheddu, A. Org. Lett. 2001, 3,
3041–3043. doi:10.1021/ol016501m
46.Gaspa, S.; Porcheddu, A.; Valentoni, A.; Garroni, S.; Enzo, S.;
De Luca, L. Eur. J. Org. Chem. 2017, 5519–5526.
doi:10.1002/ejoc.201700689
47.Martina, K.; Rotolo, L.; Porcheddu, A.; Delogu, F.; Bysouth, S. R.;
Cravotto, G.; Colacino, E. Chem. Commun. 2018, 54, 551–554.
doi:10.1039/c7cc07758k
https://www.mcam.com/it/products/engineering-plastics/engineering-80
-160-c/ertalyter-pet-p/?r=1, accessed April 6, 2019.
69.Wang, M.-L.; Huang, T.-H. Chem. Eng. Commun. 2007, 194, 618–634.
doi:10.1080/00986440600992685
48.Mocci, R.; Luca, L. D.; Delogu, F.; Porcheddu, A. Adv. Synth. Catal.
2016, 358, 3135–3144. doi:10.1002/adsc.201600350
49.Porcheddu, A.; Colacino, E.; Cravotto, G.; Delogu, F.; De Luca, L.
Beilstein J. Org. Chem. 2017, 13, 2049–2055. doi:10.3762/bjoc.13.202
50.Rightmire, N. R.; Hanusa, T. P. Dalton Trans. 2016, 45, 2352–2362.
doi:10.1039/c5dt03866a
51.Gray, N. F. Free and Combined Chlorine. In Microbiology of
Waterborne Diseases, 2nd ed.; Percival, S. L.; Yates, M. V.;
Williams, D. W.; Chalmers, R. M.; Gray, N. F., Eds.; Academic Press,
2014; pp 571–590. doi:10.1016/b978-0-12-415846-7.00031-7
52.de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Tetrahedron 1995,
51, 8023–8032. doi:10.1016/0040-4020(95)00417-7
53.Naik, N.; Braslau, R. Tetrahedron 1998, 54, 667–696.
doi:10.1016/s0040-4020(97)10061-8
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0). Please note
that the reuse, redistribution and reproduction in particular
requires that the authors and source are credited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(https://www.beilstein-journals.org/bjoc)
54.The over-oxidation product was mainly the corresponding carboxylic
acid.
55.The resulting final crude reaction is a liquid, and the reaction takes
place following an already known classical pathway for the solution
phase.
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.15.172
56.In chemical methods based on solution-phase procedures, the pH
lowering (ca. 8.6–9.5) usually accelerates the oxidation rate of this
reaction.
57.Sheldon, R. A.; Arends, I. W. C. E.; ten Brink, G.-J.; Dijksman, A.
Acc. Chem. Res. 2002, 35, 774–781. doi:10.1021/ar010075n
58.Konnert, L.; Gauliard, A.; Lamaty, F.; Martinez, J.; Colacino, E.
ACS Sustainable Chem. Eng. 2013, 1, 1186–1191.
doi:10.1021/sc4001115
59.Konnert, L.; Dimassi, M.; Gonnet, L.; Lamaty, F.; Martinez, J.;
Colacino, E. RSC Adv. 2016, 6, 36978–36986.
doi:10.1039/c6ra03222b
60.Tan, D.; Friščić, T. Eur. J. Org. Chem. 2018, 18–33.
doi:10.1002/ejoc.201700961
61.Cruz-Cabeza, A. J.; Karki, S.; Fábián, L.; Friščić, T.; Day, G. M.;
Jones, W. Chem. Commun. 2010, 46, 2224–2226.
doi:10.1039/b922955h
62.Friščić, T. J. Mater. Chem. 2010, 20, 7599–7605.
doi:10.1039/c0jm00872a
1794