Dimethyl isosorbideviaorganocatalystN-methyl pyrrolidine: scaling up, purification and concurrent reaction pathways

Article abstract of DOI:10.1039/d1cy00465d

Dimethyl isosorbide (DMI) is a well-known bio-based green replacement for conventional dipolar solvents such as dimethyl sulfoxide and dimethylformamide. The synthesis of DMI mainly relies on the etherification of the bio-based platform chemical isosorbide in the presence of basic or acid catalysts and by employing different alkylating agents. Among them, dimethyl carbonate (DMC) is considered one of the most promising for its good biodegradability and low toxicity. In this work, we report on a comprehensive investigation on high yielding methylation of isosorbideviaDMC chemistry promoted by nitrogen organocatalystN-methyl pyrrolidine (NMPy). Reaction conditions were optimized and then efficiently applied for the methylation of isosorbide epimers, isoidide and isomannide, and for some preliminary scale-up tests (up to 10 grams of isosorbide). The purification of DMI from the reaction mixture was achieved by both column chromatography and distillation at reduced pressure. NMPy demonstrated to be an excellent catalyst also for the one-pot conversion ofd-sorbitol into DMI. Furthermore, for the first time, all seven methyl and methoxycarbonyl intermediates observed in the etherification of isosorbide were synthetised, isolated and fully characterised. This has provided an insight on the concurrent reaction pathways leading to DMI and on the role played by NMPy in the methylation of isosorbide. Finally, the reaction mechanisms for the methylation, methoxycarbonylation and decarboxylation promoted by NMPy partaking in the conversion of isosorbide into DMIviaDMC chemistry have been proposed.

Full text of DOI:10.1039/d1cy00465d

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Dimethyl isosorbide via organocatalyst N-methyl
pyrrolidine: scaling up, purification and
concurrent reaction pathways†
Cite this: DOI: 10.1039/d1cy00465d
*
Mattia Annatelli, Davide Dalla Torre, Manuele Musolino
and Fabio Aricò
Dimethyl isosorbide (DMI) is a well-known bio-based green replacement for conventional dipolar solvents
such as dimethyl sulfoxide and dimethylformamide. The synthesis of DMI mainly relies on the etherification
of the bio-based platform chemical isosorbide in the presence of basic or acid catalysts and by employing
different alkylating agents. Among them, dimethyl carbonate (DMC) is considered one of the most
promising for its good biodegradability and low toxicity. In this work, we report on a comprehensive
investigation on high yielding methylation of isosorbide via DMC chemistry promoted by nitrogen
organocatalyst N-methyl pyrrolidine (NMPy). Reaction conditions were optimized and then efficiently
applied for the methylation of isosorbide epimers, isoidide and isomannide, and for some preliminary
scale-up tests (up to 10 grams of isosorbide). The purification of DMI from the reaction mixture was
achieved by both column chromatography and distillation at reduced pressure. NMPy demonstrated to be
an excellent catalyst also for the one-pot conversion of D-sorbitol into DMI. Furthermore, for the first time,
all seven methyl and methoxycarbonyl intermediates observed in the etherification of isosorbide were
synthetised, isolated and fully characterised. This has provided an insight on the concurrent reaction
pathways leading to DMI and on the role played by NMPy in the methylation of isosorbide. Finally, the
reaction mechanisms for the methylation, methoxycarbonylation and decarboxylation promoted by NMPy
partaking in the conversion of isosorbide into DMI via DMC chemistry have been proposed.
Received 17th March 2021,
Accepted 6th April 2021
DOI: 10.1039/d1cy00465d
rsc.li/catalysis
This ever-growing demand for green alternatives to
petroleum-based solvents has spurred, in the last ten years,
1. Introduction
Non aqueous solvents – still mainly produced from fossil fuel
sources – represent the vast majority of waste derived from
organic syntheses, both at laboratory and industrial scale.
The replacement of hazardous and toxic organic media with
alternatives derived from renewables is a priority to realize
more sustainable industrial processes.1
the exploitation of new bio-based reaction media. Ideally, a
biomass or waste derived solvent should encompass the
required physical–chemical properties to guarantee reagents
solubility in combination with low environmental impact,
human health preservation, sustainable lifecycle and easy
availability at competitive price.
Pharmaceutical companies, in particular, are highly
affected by the use of organic solvents that are employed in
the preparation and purification of active pharmaceutical
ingredients.2 By considering the extent of the issue,
GlaxoSmithKline, Pfizer, AstraZeneca and Sanofi, have all
established custom-made solvent guides that provide a quick
tool to select greener alternative media.3
Some relevant examples of bio-based green solvents include:
• Weak polar solvents as p-cymene, limonene, and terpinene;
•
Intermediately polar solvents as 2-MeTHF, 2,2,5,5-
tetramethyloxolane (TMO), glycerol, carbohydrates, gluconic
acid and ethyl lactate;
• Strong polar solvents as γ-valerolactone, Cyrene™ and
dimethyl isosorbide (DMI).
The viable replacement for polar aprotic and halogenated
solvents is also highlighted as one of the Key Green
Compared to the abovementioned solvents, DMI (b.p. 236 °C),
is a unique molecule due to its high polarity and water solubility
that render it a good replacement for conventional dipolar media,
such as dimethyl sulfoxide and dimethylformamide.
Chemistry research areas from
manufacturers' perspective.4
a
pharmaceutical
Dimethyl isosorbide is one of the simplest derivatives of
well-known bio-based platform chemical isosorbide
(Scheme 1), an anhydro sugar readily synthesised by
D-sorbitol dehydration reaction.5 D-Sorbitol has an estimated
global market of 800 kt per year, thus isosorbide and
Department of Environmental Sciences, Informatics and Statistics, University of Ca’
Foscari, Campus Scientifico, via Torino 155, 30172 Venezia Mestre, Italy.
E-mail: Fabio.arico@unive.it
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
d1cy00465d
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Scheme 2 DMI synthesis via DMC chemistry.
of DMC are consumed to form DMI along with the equivalent
amount of CO2 and MeOH as the only by-products formed.
It should be also mentioned that isosorbide has a peculiar
V-shaped structure that incorporates four oxygens in
β-position to each other, conferring to the molecule a high
reactivity, which is atypical of secondary alcohols.14 The
different configuration of the two hydroxyl groups, endo (–OH
group in the 2-position directed toward the V-shaped cavity)
and exo (–OH in the 5-position pointing outside of cavity),
combined with the reactivity of ambident electrophile DMC,
render the synthesis of DMI complicated by the presence of
numerous intermediates (Scheme 3) and yet captivating.
In previous investigations, the methylation of isosorbide
was carried out at the reflux temperature of DMC (90 °C) in
the presence of freshly prepared NaOMe; DMI was isolated as
pure compound in quantitative yields, however a large
amount of the strong base was required.15
In an alternative approach, isosorbide was reacted with
DMC at high pressure in autoclave (at 200 °C) in the presence
of hydrotalcite KW2000 (Mg0.7Al0.3O1.15), (1 : 1 w/w ratio).16
DMI was recovered in high yield (ca. 90%) after purification
via column chromatography, although, to ensure high activity
of the catalyst, the hydrotalcite must be calcinated overnight
at 400 °C to eliminate interstitial water.
Scheme
precursor.
1 Isosorbide as bio-based platform chemical and DMI
consequently DMI are both easily available at relatively cheap
price also in large-scale.
DMI has been efficiently used in Pd-catalysed cross-
coupling reactions i.e., Suzuki–Miyaura, Mizoroki–Heck and
Sonogashira reactions as substitute of hazardous solvents
1,4-dioxane and DMF.6 Besides, it was recently employed in
the preparation of poly(vinylidene fluoride)- and poly(ether
sulfone)-based membranes with a pore size in the range of
ultrafiltration and microfiltration that render them ideal for
applications in water treatment processes.7 DMI use in
cosmetics and as efficient thinning agent were also described
in the literature.8
Despite such wide interest, only a scarce number of
synthetic procedures to dimethyl isosorbides are reported in
the literature. Nowadays, main synthetic approaches to DMI
are based on the reaction of isosorbide with alkylating agents
including toxic halogen chemicals such as alkyl halide.9
Methanol and ethanol have been explored as viable reagents
for the synthesis of DMI and diethyl isosorbide (DEI) in the
presence of numerous catalysts, such as potassium salts of 12-
tungsto-phosporic acid, zeolites, zirconia-based catalysts.10
Isosorbide conversion was in all cases good (up to 78%),
whereas selectivity toward DMI and DEI resulted only moderate
(24 and 34% respectively).
In another approach, 1,2-dimethoxyethane was used as
reagent and solvent for isosorbide etherification, by heating
to 150 °C in the presence of heteropolyacids.11 Among them
12-tungstophosphoric acid (H3PW12O40) exhibited superior
activity leading to almost quantitative conversion of
isosorbide (>90%) with DMI selectivity up to 80%. The
catalyst was recycled three times, although the product was
never isolated from the reaction mixture.
DMI was also prepared in moderate yield (54%) by
solvent-free reaction of isosorbide with methylphosphates in
the presence of iron triflate as Lewis acid at 100 °C.12
Dialkyl carbonates (DACs), well known green solvents and
reagents,13 have been extensively investigated for the alkylation
of isosorbide. The reaction of isosorbide with DMC is highly
attractive as it combines the advantages of a bio-based starting
material with a green solvent and reagent leading to a
sustainable alternative for conventional dipolar solvents. In the
methylation reaction via DMC chemistry (Scheme 2) two moles
Few patents report additional investigations where DMI was
synthetised via DMC chemistry in the presence of Brønsted
bases at high temperature17 or employing alternative reaction
conditions (MW irradiation);18 unfortunately these procedures
were not described in detail.
Recently
a one-pot procedure to DMI starting from
D-sorbitol via DMC chemistry using nitrogen superbase 1,5,7-
triazabicyclo[4.4.0]dec-5-ene (TBD) as catalyst was also
described. The reaction was carried out in an autoclave at
high pressure and DMI selectivity was 70%.19
In this work we report on a systematic investigation on the
methylation of isosorbide via DMC chemistry promoted by
N-methyl pyrrolidine, that resulted the most efficient nitrogen
organocatalysts among the ones investigated. Reaction
conditions were first optimized to achieve quantitative
conversion and selectivity towards DMI and then tested on
isosorbide epimers, isomannide and isoidide. Preliminary scale-
up experiments (5–10 grams of isosorbide) were also carried out
and issues related to DMI purification addressed. N-Methyl
pyrrolidine was then tested in the one-pot direct conversion of
D-sorbitol into DMI resulting more efficient than TBD used as
preferred catalyst in previous investigations.18 Besides, for the
first time, all the reaction intermediates (seven compounds)
forming during the reaction of isosorbide with DMC have been
isolated and fully characterised via a custom-built synthetic
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Scheme 3 Methylation of isosorbide via DMC chemistry. The scheme outlines all the observed reaction intermediates.
Table 1 DMI via DMC chemistry and nitrogen organocatalysts
Selectivity%
#
Base
MMI1
DMI
MMI2
MCI1 MCI2
MCMI1 MCMI2
DCI
1
2
3
4
5
6
7
8
—
TBD
DBU
DABCO
Pyridine
NMPy
Et3N
1
5
13
8
19
2
5
1
78
51
54
20
98
95
94
1
0
0
0
11
0
30
0
0
0
0
0
0
0
31
17
34
38
49
0
35
0
0
0
0
0
0
0
0
0
0
0
DMAP
6
Isosorbide : DMC : catalyst 1.0 : 50.0 : 0.5 mol ratio. Reactions were conducted in autoclave at 200 °C. Pressure was 13–17 bar; isosorbide
conversion was always quantitative. Conversion and selectivity were calculated via GC-MS.
strategy. This has provided a clearer insight on the reaction
pathways leading to DMI and on the role of NMPy as the
catalyst. Finally, a mechanism for each concurrent reaction
1,4-Diazabicyclo[2.2.2]octane (DABCO) showed modest result,
meanwhile pyridine efficiency was quite poor. On the other
hand, organocatalysts incorporating aliphatic, less sterically
hindered amines such as N-methyl pyrrolidine (NMPy),
triethyl amine and 4-dimethylaminopyridine (DMAP) resulted
more efficient. In particular, NMPy led to the almost
quantitative formation of DMI and it was selected as the
preferred nitrogen organocatalyst.
contributing
to
DMI
formation,
i.e.,
methylation,
methoxycarbonylation and decarboxylation, has been proposed.
2. Results and discussion
Interestingly, the catalyst activity seems not related to its
basicity as NMPy pKa value is lower than DBU and TBD, both
less efficient in promoting isosorbide etherification.§
In this case study, the methylation of isosorbide was
conducted in an autoclave by employing DMC as reagent and
solvent in the presence of a nitrogen organocatalyst (Table 1).
Several experiments were then conducted to optimize the
reaction conditions (Table 2). Attempts to reduce the amount
of NMPy resulted in lower DMI selectivity (#1–3; Table 2). By
decreasing the reaction temperature to 180 °C, the
methylation efficiency has been affected as well. On the other
hand, when the reaction was performed at 220 °C, DMI
formed in quantitative yield in only 6 hours (#5–6; Table 2).
Scheme
3 reports all the seven reaction intermediates
forming by the combined reactivities of isosorbide and DMC,
i.e., mono- and di-methoxycarbonyl derivatives (MCI1, MCI2
and DCI), mono methyl isosorbides (MMI1 and MMI2) and
methoxycarbonyl methyl products (MCMI1 and MCMI2).‡
A first experiment was carried out reacting isosorbide and
DMC in the absence of a catalyst. The quantitative conversion
of isosorbide was observed although most of the obtained
products are methoxycarbonyl derivatives; some methylated
products were also present in the reaction mixture.
‡ All the carboxymethyl and methyl derivatives of isosorbide have been
identified according to their retention time in the GC-MS trace reported in the
supplementary information.
When superbases 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD)
and 1,5-diazabiciclo(5.4.0)undec-7-ene (DBU) were used, DMI
formed in good to moderate selectivity respectively.
§ More data reported in ESI.†
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Table 2 DMI: optimization of the reaction conditions
NMPy
T
t
Selectivity%
mol eq.
°C
h
MMI1
DMI
MMI2
MCMI1 MCMI2
1
2
3
4
5
6
7
8
9
0.50
0.35
0.25
0.50
0.50
0.50
0.50
0.50
0.50
200
200
200
180
220
220
200
200
200
12
12
12
12
12
6
6
8
10
2
5
13
6
1
1
3
4
4
98
90
67
81
99
99
85
85
92
0
0
2
0
0
0
0
0
0
0
5
18
13
0
0
12
11
4
Isosorbide : DMC : 1.0 : 50.0 mol ratio; reactions were conducted in an autoclave. Pressure was about 13–17 bar. Isosorbide conversion was
always quantitative. Selectivity and conversion were calculated via GC-MS.
Methylations performed by reducing the reaction time were
also less efficient in terms of DMI selectivity.
anhydro sugars.§ Interestingly both dimethyl isomannide
(DMIm) and dimethyl isoidide (DMIi) were achieved in
excellent selectivity (94–95%) confirming the robustness of
this synthetic procedure.§
According to data collected, the best reaction conditions
involved the heating of the reaction mixture to 200 °C for 12
h in the presence of 0.5 mol eq. of NMPy (#1; Table 2). In
fact, the test carried out at 220 °C led to a dark brown
mixture due to the presence of a certain amount of degraded
material (#5–6; Table 2).
With the optimized reaction conditions in hand, some
scale-up reactions were then performed (Table 3); the amount
of the isosorbide was increased up to 10 grams. In all
experiments (#1–4; Table 3) the selectivity toward DMI was
always almost quantitative confirming the efficiency of the
procedure.
The purification of dimethyl isosorbide from the reaction
mixture was also addressed. DMI achieved from relatively
small-scale reactions (#1–3; Table 3) was purified via column
chromatography, meanwhile the larger scale reaction (#4;
Table 3) was purified by distillation. In both cases DMI was
recovered as transparent liquid; the lower yield achieved via
distillation can be ascribed to product loss in the apparatus.
Most likely, by performing the distillation in larger scale, it
may result more efficient.
D-Sorbitol one-pot conversion into DMI promoted by
NMPy was also attempted. A first experiment was conducted
according to our previously reported best reaction
conditions.18 Thus, D-sorbitol was reacted with DMC in the
presence of NMPy at 90 °C for 48 hours to ensure high yield
cyclisation into isosorbide; then the temperature was risen to
200 °C for further 24 hours. As a result, DMI was the only
product detected in the reaction mixture via GC-MS (#2;
Table 4). By comparison with our previously reported
experiment (#1; Table 4) DMI selectivity was higher and no
epimerisation was observed, although a certain amount of
degraded material was also present in the reaction mixture
affecting the isolated yield (55%).
One-pot D-sorbitol conversion to DMI was then attempted
at 200 °C for 20 hours without any temperature variation. In
this trial DMI was still the main reaction product, but several
other isosorbide derivatives were also present in the reaction
mixture (#3; Table 4).
DMC was also recovered by quick distillation in all tests
and reused in further experiments.
Methylation of isosorbide epimers, isomannide and isoidide,
was next investigated (Scheme 4). Reactions were performed in
an autoclave at 200 °C on one- and five-grams scale of the two
2.1. Concurrent reaction pathways leading to DMI, role of the
catalyst and proposed reaction mechanisms
From a mechanistic point of view, the methylation of isosorbide
is quite complicated by numerous concomitant reaction
pathways. In this scenario, the first issue to be addressed was to
develop a strategic approach for the preparation of all seven
methoxycarbonyl and methyl derivatives, which were observed
as intermediates in the methylation of isosorbide (Scheme 5).‡
The dimethoxycarbonyl isosorbide (DCI) was easily
prepared in high yield by reaction of isosorbide with an
excess of DMC in the presence of potassium carbonate. A
Dean–Stark apparatus was set up to push the equilibrium
toward DCI that was achieved in quantitative yield.
Table 3 DMI scaling-up syntheses
Isosorbide
Selectivity%
DMI yield
G
MMI1
DMI
MMI2
%
1
2
3
4
1.0
3.0
5.0
2
1
1
8
98
99
99
92
0
0
0
0
85a
85a
75a
65b
10.0
Monocarboxymethyl isosorbides MCI1 and MCI2, reported
in the literature as intermediates of isosorbide-based
polycarbonate,20 were previously either isolated in small
amounts from complicated reaction mixture15 or more recently
Isosorbide : DMC : 1.0 : 50.0 mol ratio, 200 °C, 12 hours; reactions
were conducted in autoclave. Selectivity was calculated via GC-MS.
a
b
Purification via column chromatography.
Purification via
distillation.
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Scheme 4 Synthesis of dimethyl isomannide (eq. 1), dimethyl isoidide
(eq. 2) via DMC chemistry in the presence of N-methylpyrrolidine.
synthetised via DMC-mediated isosorbide transesterification in
the presence of a task-specific phosphonium ionic liquids.21
Herein, we developed a convenient synthesis to MCI1 and MCI2
by reacting isosorbide with a diluted solution of DMC in
acetonitrile employing 1.0 mole eq. of potassium carbonate.
Both products formed in moderate yields and were isolated as
pure compounds via column chromatography. MCI1 was the
major product (MCI1 :MCI2 ratio 2 : 1), inasmuch the
methoxycarbonylation reaction of the less sterically hindered
exo hydroxyl group was favoured.
Scheme
5
Synthetic strategy used for the preparation of
methoxycarbonyl and methyl derivatives of isosorbide.
Monomethyl derivatives MMI1 and MMI2 have been
scarcely reported in the literature.
A typical synthetic
approach for these derivatives relies on the selective
acetylation of an isosorbide (exo) hydroxyl group followed by
reaction with methyl halide and deprotection of the acetyl
moiety.22 However, we discovered that a direct methylation of
isosorbide in the presence of sub-stoichiometric amount of
All compounds depicted in Scheme
5
were fully
characterised via (1D and 2D) NMR spectroscopy and high-
resolution mass spectrometry that confirmed the proposed
structures. The identification of the stereoisomers was also
supported by comparing NMR spectra of dimethyl and
dimethoxycarboxyl derivatives of isoidide and isomannide
available in our laboratory.
By having all the possible intermediates as pure
compounds, the reaction pathway leading to DMI was further
investigated (Fig. 1). Several experiments were conducted in
the best-found reaction conditions (#6; Table 1) and
monitored over time (0–12 h). The reaction time zero was
conventionally fixed when the autoclave reached the
temperature of 200 °C. However, as isosorbide already started
iodomethane (1.0 mol eq.) led to the formation of
a
reasonable amounts of the monomethyl derivatives. In the
reaction mixture MMI1 and MMI2 were present in 1 : 4 mol
ratio due to the strong hydrogen bond involving the endo
hydroxyl group that renders it more reactive toward
alkylation. Both monomethyl derivatives were isolated as
pure compounds by purification via column chromatography.
Finally, MCMI1 and MCMI2 were synthetised in
quantitative yield by methoxycarbonylation reaction of MMI1
and MMI2 via DMC chemistry.
Table 4 D-Sorbitol direct conversion into DMI
T
t
P
Selectivity%
#
°C
h
bar
MMI1 MMI2
DMI
MCMI1 MCMI2
DCI
1a
2
3
90/200
90/200
200
48/24
48/24
20
26
30
20
0
0
29
69
100b
55
00
0
5
0
0
11
a
Isosorbide : DMC : NMPy 1.0 : 50.0 : 1.0 mol ratio; reactions were conducted in autoclave. Selectivity was calculated via GC-MS. TBD was used
as the catalyst.18 b Isolated yield via column chromatography was 55%; a certain amount of insoluble (degraded) material was present in the
reaction mixture.
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Fig. 1 Methylation of isosorbide over time.§
reacting with DMC at lower temperatures (#1; Table 1), three
extra experiments were conducted by heating the mixture to
120, 140 and 160 °C. These temperatures were reached at 30,
20 and 10 minutes before the reaction time zero and are
reported in Fig. 1 with negative values (−0.50, −0.33 and
−0.16 hour, respectively).
Fig. 2 From isosorbide to DMI via DMC: possible reaction pathways.
All the experiments were conducted separately rather than
performing sampling on a single trial and each reaction was
repeated twice to confirm results reliability.§
Data collected showed that monomethyl derivatives MMI1-
2 are present in trace, meanwhile MCI1-2 formed rapidly in
As expected, the conversion of isosorbide was already
quantitative when the autoclave reached the 200 °C. DCI and
the two monocarboxymethyl derivatives MCI1 and MCI2,
once formed, were promptly converted in the other
intermediates. MMI2 formed in larger amount and more
rapidly than MMI1 due to higher reactivity of the endo
hydroxyl group. Furthermore, MMI1 resulted the less reactive
derivatives as it was the only intermediate still present in the
reaction mixture after 8 hours.
According to these data, in Fig. 2 a comprehensive
overview of all the possible concurrent reaction pathways
leading to DMI via DMC chemistry is depicted. Three
different reactions might take place: i) methoxycarbonylation
via BAc2 mechanism; ii) methylation via BAl2 mechanism and
iii) decarboxylation (Fig. 3). Thus, as an example, formation
of isosorbide methyl derivatives MMI1-2 and DMI may occur
either via direct methylation reaction via BAl2 mechanism or
via decarboxylation of methoxycarbonyl monomers (MCI1-2,
MCMI1-2 and DCI).
large
amount,
probably
due
to
the
existing
thermodynamically driven equilibrium (BAc2 mechanism).
After 12 hours small amounts of MMI1 and MCMI derivatives
are still present in the reaction mixture, even if DMI
selectivity (84%) was comparable to the previously observed
results. Although this experiment seems to suggest that the
decarboxylation is partaking to the formation of DMI, it
cannot be excluded that dimethyl isosorbide formed via BAc2
equilibrium reaction followed by BAl2 direct methylation of
the hydroxylic groups. In this view, DCI decarboxylation was
tested without DMC employing 2-methyl tetrahydrofuran
(2-MeTHF) and acetonitrile as reaction media (#2–3; Table 5).
In the literature, DACs decarboxylation has been
extensively reported as viable route to achieve symmetrical
and unsymmetrical DACs, however it required high
temperature and the presence of a proper catalyst.23
For the scope of our investigation some decarboxylation
experiments
were
conducted
by
employing
dimethoxycarbonyl isosorbide as reaction substrate (Fig. 3;
Table 5).
When pure DCI was reacted with DMC at 200 °C and in
the presence of NMPy, DMI was the major product observed.
Fig. 3 reports on the reaction pathway observed in the
conversion of DCI into DMI (#1; Table 5).
Fig. 3 DCI decarboxylation reaction.
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Table 5 DCI conversion into DMI
Selectivity%
MMI1 DMI
#
Catalyst
Solvent
MMI2
Others
1
2
3
4
NMPy
NMPy
NMPy
DMPyC
DMC
6
23
35
46
86
6
5
0
67
59
9
8
4
0
0
2-MeTHF
CH3CN
CH3CN
45
Isosorbide : DMC : catalyst 1.0 : 0.5 mol eq. in 30 mL of solvent;
temperature 200 °C, autogenous pression 15–17 bar.
Scheme 7 Etherification of isosorbide catalysed by DMPyC (eq. 1);
In both experiments, monomethyl derivatives MMI1 and
MMI2 were the major products, while only traces of DMI
were observed.
decarboxylation of DCI catalysed by DMPyC.
In order to better understand these results, the role of
N-methylpyrrolidine in the synthesis of DMI needed to be
disclosed. In our reaction conditions, the nitrogen atom of
NMPy, can easily react as a nucleophile with DMC leading to
a N,N-dimethylpyrrolidinium methylcarbonate (DMPyC). This
compound was already reported in the literature and a
sample was then prepared and collected for further study
(Scheme 6).24 The evidence of its presence in the
etherification of isosorbide was confirmed by carrying out a
test reaction between NMPy and DMC at 200 °C for 12 hours.
Although NMPy resulted fully converted and DMPyC was
present and observable up to 160 °C, NMR studies of the
final reaction mixture (after 12 hours) showed the presence
of other unforeseen products barely identifiable through
spectra interpretation. Interestingly, a recent investigation on
pyrrolidinium cations stability demonstrated that N,N-
dimethyl pyrrolidinium ions are not stable in basic
conditions at high temperature degrading via pyrrolidinium
ring opening in a linear amine (Scheme 6).25 In fact when a
thermogravimetric analysis on freshly prepared pyrrolidinium
methylcarbonate DMPyC was carried out, a slow degradation
process was detectable starting at 160 °C.§ Most likely, in the
adopted reaction conditions, the basic environment can be
ascribed to the methoxycarbonate anion or to methoxide
formed by its degradation. The so-formed trialkylamine can
eventually methylate once again to the corresponding linear
tetraalkyl ammonium ion (Scheme 6) that might also aid the
methylation of isosorbide.
DMPyC was then tested in the conversion of DCI into DMI
(eq. 2; Scheme 7) resulting more efficient than NMPy itself
(#4; Table 5). The experiment was performed in CH3CN in
order to avoid any other concurrent reactions that might take
place in the presence of DMC and led to DMI in 45% selectivity.
This result clearly explained the data observed in the
previous decarboxylation experiments (#1–3; Table 5). In the
absence of DMC, NMPy first reacts with DCI to give the
pyrrolidinium species that then promotes the decarboxylation
of the residual methoxycarbonates moieties giving mostly
MMI derivatives. The reaction conducted in the presence of
DMPyC not only confirmed that the decarboxylation is one of
the concurrent reactions leading to DMI, but also outlined
that the tetra alkyl ammonium species were the most active
catalysts in the etherification of isosorbide. The evidence that
the DCI decarboxylation was not quantitative in the presence
of DMPyC accounts for the complexity of the overall reaction
mechanism. Most probably, this reaction contributes only to
some extent to DMI formation that is also supported by
direct methylation via BAl2 mechanism.
By considering these observations, a better understanding
of the three reaction mechanisms partaking in the
methylation of isosorbide was attained. Fig. 4 reports the
proposed mechanisms for the methoxycarbonylation,
methylation and decarboxylation reactions contributing to
the formation of DMI. As above mentioned, the most
effective catalytic species are the quaternary ammonium salts
eventually aided by the methyl carbonate anion. Most
probably in the methoxycarbonylation and methylation
reactions there is a cooperative effect of DMPyC cation and
anion where the first activates DMC, while the latter acts as a
base on isosorbide hydroxylic groups (Fig. 4). In the
literature, a similar mechanism was already reported for
methoxycarbonylation of isosorbide catalysed by several
nitrogen organocatalysts.26
As further proof, isosorbide was reacted with DMC in the
presence of freshly prepared DMPyC (0.5 mol eq.) and indeed
DMI was obtained in high yield (90% yield), confirming the
catalytic activity of the pyrrolidinium ion (eq. 1; Scheme 7).
Regarding the decarboxylation reaction, it could be
assumed that it is promoted mostly by the quaternary
ammonium salts. The isosorbide methoxycarbonyl moiety
most probably undergoes CO2 elimination via a four-member
intermediate that was already described as typical route for
DACs pyrolysis.23
Scheme 6 Catalytic species promoting the methylation of isosorbide.
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Fig. 4 Possible reaction mechanisms for the methoxycarbonylation, methylation and decarboxylation of isosorbide and its derivatives.
3. Experimental
General
mixture was analysed via GC-MS to evaluate conversion of the
substrate and products selectivity.
DMI was obtained as pure via chromatographic column
(Et2O/n-hexane 7/3; Rf = 0.80). The pure compound was
isolated as a light yellow liquid in 85% yield (1.01 g).
1H NMR (400 MHz CDCl3) δ ppm = 4.64 (t, 1H), 4.54 (d,
1H), 3.89–3.88 (m, 4H), 3.85 (m, 1H), 3.61–3.53 (m, 1H), 3.49
(s, 3H), 3.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ ppm =
85.8, 81.7, 79.9, 72.9, 69.7, 58.1, 57.1. HRMS: m/z [M + H]+
calc. for [C8H14O4 + H]+: 175.0965; found: 175.0967.
All reagents and solvents were purchased from Sigma
Aldrich.
The reactions were monitored through GC-MS (GC System
6890N; Agilent Technologies mass selective detector 5973)
with chromatography column (HP-5MS). Compounds were
injected with micro-syringe Hamilton (10 μL).
NMR spectra were recorded with Bruker 300 MHz and 400
MHz spectrometer, in CDCl3, CD3OD and D2O.
The high-pressure reactions were conducted in autoclave
(capacity 220 mL) with thermocouple for the control of
temperature and under magnetic stirring.
Synthesis of dimethyl isosorbide – large scale (#4; Table 3)
In a typical reaction in autoclave, 10.00 g of isosorbide (68.4
mmol, 1.0 mol eq.) was reacted with 100 mL of dimethyl
carbonate (1.18 mol, 18.0 mol eq.) in presence of 2.91 g of
N-methyl pyrrolidine as base (34.1 mmol, 0.5 mol eq.), at 200
°C for 12 h. The autogenous pressure reached the value of 31
bar. After cooling, the reaction crude was filtered and
analysed via GC-MS to evaluate conversion of the substrate
and products selectivity. The product was obtained as pure
via vacuum distillation (T = 110 °C, p = 40 mbar ca.) as a
yellowish liquid in 65% yield (7.73 g).
HR-MS spectra for have been acquired by means of Bruker
compact QTOF with a mass resolution of 30 000 in positive
polarity mode. The mass calibration has been conducted
using a sodium formate cluster's solution and the data have
been processed in a HPC mode. The acquisition has been
conducted in full scan mode in the range of 50 to 500 m/z,
with a 4 l min−1 at 180 °C of source dry gas. The ion formula
of each compound has been calculated with the Smart
formula tool within the Bruker software platform, using a 4
mDa of mass confidence and considering the isotopic pattern
ratio.
Thermogravimetric analysis was recorded with INSEIS STA
PT-1000, starting from 30 °C to 500 °C with a temperature
ramp rate of 10 °C min−1, under nitrogen flow.
Synthesis of dimethyl isosorbide from isosorbide (#2; Table 4)
In a typical reaction in autoclave, 2.00 g of D-sorbitol (10.97
mmol, 1.0 mol eq.) was reacted with 47 mL of dimethyl
carbonate (0.55 mmol, 50.0 mol eq.) in presence of 0.91 g of
N-methyl pyrrolidine as base (10.91 mmol, 1.0 mol eq.), at 90
°C for 48 h then 200 °C for 24 h. After cooling, the reaction
crude was filtered and concentrated via rotavapor. The
resulting mixture was analysed via GC-MS to evaluate
conversion of the substrate and products selectivity.
Synthesis of dimethyl isosorbide (#4; Table 1)
In a typical reaction in an autoclave, 1.00 g of isosorbide
(6.84 mmol, 1.0 mol eq.) was reacted with 30 mL of dimethyl
carbonate (0.35 mol, 50.0 mol eq.) in presence of 0.29 g of
N-methyl pyrrolidine as base (3.41 mmol, 0.5 mol eq.), at 200
°C for 12 h. The autogenous pressure reached the value of 20
bar. After cooling, the reaction crude was filtered and
concentrated under vacuum via rotavapor. The resulting
The product was obtained as pure via chromatographic
column in 55% yield (1.02 g).
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Synthesis of dimethyl Isoidide (DMIi)
6.84 mmol, 1.0 mol eq.) were reacted in 20 mL of acetonitrile,
at 80 °C for 42 h. After cooling, the reaction crude was
filtered and concentrated under vacuum via rotavapor.
The products were obtained as pure via chromatographic
column (n-hexane/EtOAc 7/3; RfMCI1 = 0.3, RfMCI2 = 0.2).
The pure MCI1 was isolated as a white solid in 33% yield
(0.49 g). 1H NMR (400 MHz CDCl3) δ ppm = 5.17–5.15 (m,
1H), 4.68 (t, 1H), 4.57–4.55 (m, 1H), 4.35 (m, 1H), 4.17–4.14
(dd, 1H), 4.06–4.02 (dd, 1H), 3.94–3.90 (m, 1H), 3.80 (s, 3H),
3.63–3.59 (m, 1H). 13C NMR (100 MHz, CDCl3) δ ppm = 154.7,
85.4, 81.9, 81.6, 73.6, 73.3, 72.3, 55.1. HRMS: m/z [M + H]+
calc. for [C8H12O6 + H]+: 205.0707; found: 205.0706.
The pure MCI2 was isolated as a white solid in 16% yield
(0.23 g). 1H NMR (400 MHz CDCl3) δ ppm = 5.11–5.07(m,
1H), 4.93–4.91 (t, 1H), 4.44–4.43 (d, 1H), 4.38–4.36 (m, 1H),
3.95 (m, 2H), 3.93–3.86 (m, 2H), 3.84 (s, 3H). 13C NMR (100
MHz, CDCl3) δ ppm = 155.2, 88.4, 80.4, 76.9, 76.3, 75.7, 70.4,
55.1. HRMS: m/z [M + H]+ calc. for [C8H12O6 + H]+: 205.0707;
found: 205.0706.
In an autoclave, 1.00 g of isoidide (6.84 mmol, 1.00 mol eq.)
was reacted with 30 mL of dimethyl carbonate (0.35 mol,
50.00 mol eq.) in presence of 0.29 g of N-methyl pyrrolidine
as base (3.41 mmol, 0.50 mol eq.), at 200 °C for 12 h. The
autogenous pressure reached the value of 20 bar.
After cooling, the reaction crude was filtered and
concentrated under vacuum via rotavapor. The resulting
mixture was analysed via GC-MS to evaluate conversion of the
substrate and products selectivity.
The product was obtained as pure via chromatographic
column (Et2O/n-hexane 1/1; Rf = 0.30). The pure compound
was isolated as a yellowish liquid.
1H NMR (400 MHz CDCl3) δ ppm = 4.61 (s, 2H), 3.91–3.83
(m, 6 H), 3.40 (s, 6H). 13C NMR (100 MHz, CDCl3) δ ppm =
85.1, 84.9, 71.8, 57.2.
Synthesis of dimethyl Isomannide (DMIm)
In an autoclave, 1.00 g of isoidide (6.84 mmol, 1.0 mol eq.)
was reacted with 30 mL of dimethyl carbonate (0.35 mol, 50.0
mol eq.) in presence of 0.29 g of N-methyl pyrrolidine as base
(3.41 mmol, 0.5 mol eq.), at 200 °C for 12 h. The autogenous
pressure reached the value of 20 bar.
After cooling, the reaction crude was filtered and
concentrated under vacuum via rotavapor. The resulting
mixture was analysed via GC-MS to evaluate conversion of the
substrate and products selectivity.
Synthesis of monomethyl isosorbides – MMI1 and MMI2
To a solution of D-isosorbide (1.00 g, 6.84 mmol) in THF (30
mL), NaH 60% w/w (0.27 g, 6.84 mmol) was added under N2
atmosphere. Then the mixture was cooled to 0 °C and a
solution of CH3I (0.43 mL, 6.84 mmol) in THF (10 mL) was
added dropwise within 15 min. The ice bath was removed,
and the mixture was heated to 60 °C for 20 h under stirring.
The mixture at this point appears as a clear orange solution.
This solution was quenched with MeOH (2 mL) and
concentrated under vacuum to give a crude product.
The product was obtained as pure via chromatographic
column (Et2O/n-hexane 6/4; Rf = 0.40). The pure compound
was isolated as an amber coloured solid.
1H NMR (400 MHz CDCl3) δ ppm = 4.53 (m, 2H), 4.01 (t,
2H), 3.90 (m, 2H), 3.63 (t, 2H), 3.40 (s, 6H). 13C NMR (100
MHz, CDCl3) δ ppm = 81.9, 80.3, 70.9, 58.3.
The products were obtained as pure via chromatographic
column (DCM/MeOH 7/3; RfMMI1 = 0.3, RfMMI2 = 0.2).
The pure MMI1 was isolated as a yellow oil in 35% yield
1
(0.39 g). H NMR (400 MHz CDCl3) δ ppm = 4.53 (t, 1H), 4.40
(d, 1H), 4.21 (m, 1H), 4.01–3.97 (m, 1H), 3.85 (dd, 1H), 3.84–
3.77 (m, 2H), 3.53–3.49 (m, 1H), 3.32 (s, 3H). 13C NMR (100
MHz, CDCl3) δ ppm = 85.6, 85.4, 81.7, 73.6, 73.0, 72.2, 57.2.
HRMS: m/z [M + H]+ calc. for [C7H12O4 + H]+: 161.0808;
found: 161.0812.
Synthesis of dicarboxymethyl isosorbide (DCI)
In a 250 mL double-necked bottom round flask equipped
with a Dean–Stark trap and condenser, 5 g of isosorbide
(34.21 mmol, 1.0 mol eq.) was reacted with 90 mL of
dimethyl carbonate (1.07 mol, 30.0 mol eq.) in presence of
K2CO3 as base (0.95 g, 6.80 mmol, 0.2 mol eq.), at 90 °C for 6
h. After cooling, the reaction crude was filtered and
concentrated under vacuum via rotavapor to achieve DCI.
The pure MMI2 was isolated as a pale-yellow oil in 15%
1
yield (0.16 g). H NMR (400 MHz CDCl3) δ ppm = 4.67 (t, 1H),
4.40–4.38 (m, 1H), 4.27–4.25 (m, 1H), 3.92–3.85 (m, 4H),
3.54–3.48 (m, 1H), 3.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
ppm = 88.4, 81.8, 79.8, 76.8, 75.9, 70.0, 58.3. HRMS: m/z [M +
H]+ calc. for [C7H12O4 + H]+: 161.0808; found: 161.0812.
A
pure sample of DCI was obtained as via
chromatographic column (DCM/MeOH 99/4; Rf = 0.50).
1H NMR (400 MHz CDCl3) δ ppm = 5.13–5.12 (m, 1H),
5.10–5.08 (t, 1H), 4.92–4.89 (t, 1H), 4.57–4.56 (d, 1H), 4.12–
4.02 (m, 2H), 3.97–3.89 (m, 2H), 3.84 (s, 3H), 3.83 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ ppm = 155.1, 154.8, 85.9, 81.2, 80.8,
76.7, 73.2, 70.5, 55.1, 55.1. HRMS: m/z [M + H]+ calc. for
[C10H14O8 + H]+: 263.0761; found: 263.0766.
Synthesis of monomethylcarboxy methyl isosorbide – MCMI1
MMI2 (0.20 g, 1.25 mmol, 1.0 mol eq.), dimethyl carbonate
(7.50 mL, 89.10 mmol, 72.0 mol eq.), K2CO3 (0.35 g, 2.50
mmol, 2.0 mol eq.) were reacted at 90 °C for 24 h, in a 25 mL
bottom round flask. After 24 h, potassium carbonate (0.175 g,
1.25 mmol, 1.0 mol eq.) was added to mixture reaction and it
was left for another 24 h. After cooling, the reaction crude
was filtered and concentrated under vacuum via rotavapor.
Synthesis of monocarboxymethyl isosorbides MCI1 and MCI2
Isosorbide (1.00 g, 6.84 mmol, 1.0 mol eq.), dimethyl
carbonate (2.88 mL, 34.20 mmol, 5.0 mol eq.), K2CO3 (0.95 g,
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The product was obtained as pure without purification as
a clear oil in 99% of yield (0.23 g). H NMR (400 MHz CDCl3)
A synthetic strategy was developed so to prepare all the
seven methoxycarbonyl and methyl derivatives of isosorbide,
intermediates forming during the methylation reaction. This
approach has allowed to study in more detail the reaction
pathway leading to DMI, which includes three concurrent
reactions, i.e., methylation, methoxycarbonylation and
decarboxylation. In particular, the investigation conducted on
the less studied decarboxylation reaction of DCI showed that
the most active catalytic species are the N,N-dimethyl
pyrrolidinium methylcarbonate and eventually its tetraalkyl
ammonium derivative formed via pyrrolidinium ring opening.
This observation also explains why the catalyst basicity is not
a prominent factor in promoting the methylation reaction. In
fact, most probably it is the high NMPy nucleophilicity,
1
δ ppm = 5.10–5.08 (m, 1H), 4.74–4.72 (t, 1H), 4.60–4.58 (m,
1H), 4.10–4.09 (t, 2H), 4.00–3.94 (m, 2H), 3.8 (s, 3H), 3.66–
3.62 (m, 1H), 3.49–3.48 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
ppm = 154.8, 86.2, 81.7, 81.6, 80.3, 73.4, 70.1, 58.3, 55.0.
HRMS: m/z [M + H]+ calc. for [C9H14O6 + H]+: 219.0863;
found: 219.0869.
Synthesis of monomethylcarboxy methyl isosorbide – MCMI2
MMI1 (0.20 g, 1.25 mmol, 1.0 mol eq.), dimethyl carbonate
(7.50 mL, 89.10 mmol, 72.0 mol eq.), K2CO3 (0.35 g, 2.50
mmol, 2.0 mol eq.) were reacted at 90 °C for 24 h, in a 25 mL
bottom round flask. After 24 h, potassium carbonate (0.175 g,
1.25 mmol, 1.0 mol eq.) was added to mixture reaction and it
was left for another 24 h. After cooling, the reaction crude
was filtered and concentrated under vacuum via rotavapor.
The product was obtained as pure without further
purification as a clear oil in 99% of yield (0.23 g). 1H NMR
(400 MHz CDCl3) δ ppm = 5.00–4.96 (m,1H), 4.77–4.74 (t,
1H), 4.41–4.40 (d, 1H), 3.94–3.91 (m, 1H), 3.86–3.83 (m, 4H),
3.80 (s, 3H), 3.30 (s, 3H). 13C NMR (100 MHz, CDCl3) δ ppm =
155.2, 85.9, 85.8, 80.6, 76.9, 72.9, 70.2, 57.0, 55.1. HRMS: m/z
[M + H]+ calc. for [C9H14O6 + H]+: 219.0863; found: 219.0869.
promoting the pyrrolidinium formation, that has
predominant effect of the reaction outcome.
a
Finally, a reaction mechanism was proposed for each
reaction involved in DMI formation. It is suggested that the
anion and cation of the active specie N,N-dimethyl
pyrrolidinium methylcarbonate both support isosorbide in
the methoxycarbonylation and the methylation reaction by
coordinating an hydroxyl moiety and the DMC oxygen atoms
(cation). The decarboxylation reaction may be a typical four
membered intermediate with CO2 release, already reported in
the literature for DAC pyrolysis reactions.
In conclusion this work represents
a comprehensive
Synthesis del N,N-dimethyl pyrrolidinium methylcarbonate
investigation on isosorbide methylation via DMC chemistry
that might open the way to further exploitation also on large
scale reactions. In particular the use of continuous-flow in
combination with an efficient catalytic system could be the
key for the development of a more sustainable synthetic
approach to DMI at industrial scale.
N,N-Dimethyl pyrrolidinium methylcarbonate was prepared
accordingly the procedure previously reported in the
literature.24
1H NMR (400 MHz D2O) δ ppm = 3.45 (m, 4H), 3.28 (s,
3H), 3.07 (s,6H), 2.17 (m, 4H). 13C NMR (100 MHz, D2O) δ
ppm = 160.2, 66.8, 51.6, 48.8, 21.6.
Author contributions
Decarboxylation of DCI
Dr. Mattia Annatelli, Dr. Manuele Musolino and Davide Dalla
Torre: investigation, data curation and some conceptualization.
Prof F. Aricò: conceptualization, visualization and writing.
In a typical reaction in autoclave, 1.79 g of DCI (6.84 mmol,
1.00 mol eq.) was reacted with 30 mL of dimethyl carbonate
(0.35 mol, 50.0 mol eq.) in presence of 0.29 g of N-methyl
pyrrolidine as base (3.41 mmol, 0.5 mol eq.), at 200 °C for 12
h. The autogenous pressure reached the value 20 bar.
After cooling, the reaction crude was filtered and
concentrated via rotavapor. The resulting mixture was
analysed via GC-MS to evaluate conversion of the substrate
and products selectivity.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work was financially supported by the Organization for
the Prohibition of Chemical Weapons (OPCW); Project
Number L/ICA/ICB/218789/19.
4. Conclusions
In this work, we have explored the activity of various nitrogen
organocatalysts in the conversion of isosorbide into DMI via
DMC chemistry. The reaction conditions for the
etherification of isosorbide in the presence of NMPy have
been optimized and efficiently employed in larger scale
reaction, as well as, for the synthesis of dimethyl isomannide
and dimethyl isoidide. Purification of DMI was achieved both
by column chromatography and distillation.
Notes and references
1 (a) F. Gao, R. Bai, F. Ferlin, L. Vaccaro, M. Li and Y. Gu,
Green Chem., 2020, 22, 6240–6257; (b) A. Jordan, P. Stoy and
H. F. Sneddon, Chem. Rev., 2021, 121(3), 1582–1622.
2 R. A. Sheldon, Green Chem., 2017, 19, 18–43.
3 (a) K. Alfonsi, J. Colberg, P. J. Dunn, T. Fevig, S. Jennings, T. A.
Johnson, H. P. Kleine, C. Knight, M. A. Nagy, D. A. Perry and M.
Catal. Sci. Technol.
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View Article Online
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Paper
Stefaniak, Green Chem., 2008, 10, 31–36; (b) D. Prat, O.
Pardigon, H. W. Flemming, S. Letestu, V. Ducandas, P. Isnard,
E. Guntrum, T. Senac, S. Ruisseau, P. Cruciani and P. Hosek,
Org. Process Res. Dev., 2013, 17, 1517–1525; (c) L. J. Diorazio,
D. R. J. Hose and N. K. Adlington, Org. Process Res. Dev.,
2016, 20, 760–773; (d) C. M. Alder, J. D. Hayler, R. K.
Henderson, A. M. Redman, L. Shukla, L. E. Shuster and H. F.
Sneddon, Green Chem., 2016, 18, 3879–3890; (e) J. Esteban, A. J.
Vorholt and W. Leitner, Green Chem., 2020, 22, 2097–2128.
4 M. C. Bryan, P. J. Dunn, D. Entwistle, F. Gallou, S. G. Koenig,
J. D. Hayler, M. R. Hickey, S. Hughes, M. E. Kopach, G.
Moine, P. Richardson, F. Roschangar, A. Steven and F. J.
Weiberth, Green Chem., 2018, 20, 5082.
5 F. Aricò, Curr. Opin. Green Sustain. Chem., 2020, 21, 82–88.
6 (a) A. Watson, K. Wilson, J. Murray, H. Sneddon and C.
Jamieson, Synlett, 2018, 29, 2293–2297; (b) J. Sherwood,
Beilstein J. Org. Chem., 2020, 16, 1001–1005.
7 F. Russo, F. Galiano, F. Pedace, F. Aricò and A. Figoli, ACS
Sustainable Chem. Eng., 2020, 8, 659–668.
8 M. Windisch and H. Wieland, EP2574329, 2013.
9 (a) P. Fuertes and V. Wiatz, WO 2007/096511 Al, 2007; (b) A.
East, M. Jaffe, Y. Zhang and L. H. Catalani, US2008/0021209
A1, 2008; (c) S. Chatti, M. Bortolussi and A. Loupy,
Tetrahedron, 2001, 57, 4365–4370; (d) S. Chatti, M. Bortolussi
and A. Loupy, Tetrahedron Lett., 2001, 41, 3367–3370.
10 M. Ibert, N. Essayem, C. Feche and A. Perrard, US9321783,
2016.
14 G. Flèche and M. Huchette, Starch/Staerke, 1986, 38, 26–30.
15 P. Tundo, F. Aricò, G. Gauthier, L. Rossi, A. E. Rosamilia,
H. S. Bevinakatti, R. L. Sievert and C. P. Newman,
ChemSusChem, 2010, 3, 566–570.
16 F. Aricò and P. Tundo, Beilstein J. Org. Chem., 2016, 12,
2256–2266.
17 K. Stensrud and P. Venkitasubramanian, WO2015/094716,
2015.
18 J. S. Howard and A. J. Sanborn, WO12/015616 A1, 2015.
19 F. Aricò, A. S. Aldoshin and P. Tundo, ChemSusChem,
2017, 10, 53–57.
20 (a) W. Qian, X. Ma, L. Liu, L. Deng, Q. Su, R. Bai, Z. Zhang,
H. Gou, L. Dong, W. Cheng and F. Xu, Green Chem.,
2020, 22, 5357–5368; (b) W. Qian, L. Liu, Z. Zhang, Q. Su, W.
Zhao, W. Cheng, L. Dong, Z. Yang, R. Bai, F. Xu, Y. Zhang
and S. Zhang, Green Chem., 2020, 22, 2488–2497.
21 W. Qian, X. Tan, Q. Su, W. Cheng, F. Xu, L. Dong and S.
Zhang, ChemSusChem, 2019, 12, 1169–1178.
22 (a) D. Abenhaïm, A. Loupy, L. Munnier, R. Tamion, F.
Marsais and G. Quéguiner, Carbohydr. Res., 1994, 261,
255–266; (b) A. L. Shaikh, A. S. Kale, Md. Abrar Shaikh, V. G.
Puranik and A. R. A. S. Deshmukh, Tetrahedron, 2007, 63,
3380–3388.
23 P. Tundo, F. Arico, A. E. Rosamilia and S. Memoli, Green
Chem., 2008, 10, 1182.
24 C. Chiappe, A. Sanzone and P. J. Dysonb, Green Chem.,
2011, 13, 1437–1441.
11 P. Che, F. Lu, X. Si and J. Xu, RSC Adv., 2015, 5, 24139–24143.
12 M.-C. Duclos, A. Herbinski, A.-S. Mora, E. Métay and M.
Lemaire, ChemSusChem, 2018, 11, 547–551.
13 P. Tundo, M. Musolino and F. Aricò, Green Chem., 2018, 20,
28–85.
25 F. Gu, H. Dong, Y. Li, Z. Sun and F. Yan, Macromolecules,
2014, 47, 6740–6747.
26 J. R. Ochoa-Gómez, L. Lorenzo-Ibarreta, C. Diñeiro-Garcìa
and O. Gómez-Jiménez-Aberasturi, RSC Adv., 2020, 10,
18728–18739.
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