Micelle-enabled clean and selective sulfonylation of polyfluoroarenes in water under mild conditions

Article abstract of DOI:10.1039/c7gc03514d

Proline-based designer surfactant FI-750-M has been demonstrated to enable selective nucleophilic aromatic substitution of polyfluoro(hetero)arenes by sulfinate salts in water under mild micellar conditions. Resultant sulfones were obtained from diverse s

Full text of DOI:10.1039/c7gc03514d

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Micelle-Enabled Clean and Selective Sulfonylation of
Polyfluoroarenes in Water Under Mild Conditions
Received 00th January 20xx,
Accepted 00th January 20xx
Justin D. Smith,a Tharique N. Ansari,a Martin P. Andersson,b Yadagiri Dongari,a Faisal Ibrahim,a
Shengzong Liang,a Gerald B. Hammond,a Fabrice Gallou,c Sachin Handa,a*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Proline-based designer surfactant FI-750-M has been demonstrated the health and environmental concerns associated with these
to enable selective nucleophilic aromatic substitution of solvents have led to increasing restrictions in the EU under the
polyfluoro(hetero)arenes by sulfinate salts in water under mild REACH Regulation.13
micellar conditions. Resultant sulfones were obtained from diverse
substrates in good yields without side product formation and could
usually be purified by simple filtration. The nature of micelles of FI-
750-M and the solubility of coupling partners in different micellar
regions has been supported by dynamic light scattering, cryo-TEM,
and DFT calculations.
With the advent of micellar catalysis, significant headway has
been made toward not only replacement of organic solvents but
also achievement of transformations with very low catalyst
loadings under mild conditions.1 Recently, the domain of these
non-traditional reaction media has broadened, and systems
ranging from enzymatic catalysis to nanocatalysis are now
possible at an industrial scale under micellar or completely
Figure 1 FI-750-M, a designer amphiphile enabeling clean sulfonylation.
aqueous conditions with perfect reproducibility and low E
The SNAr chemistry reported by Lipshutz and co-workers
factor.2 Work by Kobayashi,3 Krause,4 Lipshutz,5 and Uozumi6 in
involved aromatic chlorides and fluorides with non-ionic
this area to address the issues described by Sheldon in his many
nucleophiles in water using TPGS-750-M amphiphiles and
reviews7 is highly compelling. Reports of challenging transition-
achieved low E-factors with mild conditions. However,
metal-free processes in micellar media have been sparse;8
transformations involving ionic nucleophiles are still considered
however, in 2015 Lipshutz and co-workers reported
problematic in micellar media, which may be due to the
nucleophilic aromatic substitutions (SNAr) in water, limited to
association of the nucleophilic ion with water, preventing the
neutral nucleophiles.8d SNAr is a highly important and useful
category of organic transformation offering atom-economy,
metal-free conditions, and complementarity of reactivity with
cross-coupling reactions.9 Unfortunately, these reactions are
predominantly studied and conducted in organic media with
over 50% of cases using highly toxic and problematic solvents
such as DMF, DMAc, NMP, etc.10 These solvents pose serious
health risks to the liver, kidney, spleen, thymus, and brain and
also impair embryo-fetal development.11 NMP is also listed
under California’s Prop 65 as a developmental toxin.12 Similarly,
desired reactivity.14 Typically, transformations with ionic
nucleophiles require polar aprotic solvent and high reaction
temperature, as exemplified by the traditional syntheses of
(hetero)arylsulfones and polyfluorarylsulfones.15 Oftentimes,
transition metal catalysts are also required.16
Along the same lines, (hetero)arylsulfone scaffolds have
applications as reaction intermediates in synthesis of medicinal
compounds,17 and dyes.18 Among this class of compounds,
polyfluoroarylsulfone has applications in synthesis of materials
for membrane gas separation19 and also have potential
applications in photocatalysis20 A typical two-step route to
synthesis of polyfluoroarylsulfone, first developed by Tatlow, is
the SNAr reaction of highly activated polyfluoroaryl substrates
with a hot solution of sodium thiophenoxide in refluxing
pyridine followed by oxidation of the resulting sulfide under
a. Department of Chemistry, 2320 S. Brook St., University of Louisville, Louisville, KY
40292 (USA).
b. Nano-Science Center, Department of Chemistry, University of Copenhagen
(Denmark)
c. Novartis Pharma AG, Basel CH-4002 Switzerland.
*sachin.handa@louisville.edu.
Electronic Supplementary Information (ESI) available: [reaction optimization,
physical data of FI-750-M, computational details, analytical data of products]. See
DOI: 10.1039/x0xx00000x
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very harsh conditions.15a In a separate report by Haszeldine and
coworkers, a similar product was synthesized through reaction
of the highly activated pentafluoropyridine system with
phenysulfinate salt in refluxing DMF.15c These methods lack
demonstrated substrate scope and suffer from limited
functional group tolerance. Under such conditions, many
functionalities are incompatible, including esters, carbamates,
nitriles, nitro groups, and thiocarbamates. Furthermore,
handling thiols is often unpleasant. Therefore, a general, direct,
and selective method for sulfonylation of polyfluoroarenes
under ambient conditions in a greener medium, i.e., recyclable
water, is desirable. We sought to develop such a method by
leveraging synergistic local micellar effects of the newly
engineered, environmentally benign amphiphile FI-750-M,
which can mimic toxic polar organic solvents such as DMF, 1,4-
dioxane, NMP, etc.1d
We propose that when dissolved in water, FI-750-M forms
nanomicelles with different binding sites (Figure 1, see FI-750-
M) for polyfluoroarenes and sulfinate salts; i.e., i) the inner
lipophilic region (shown in black), ii) the proline linker (shown in
blue), and iii) the mPEG region (shown in orange). Such an
arrangement could bring nucleophiles, including anionic weak
nucleophiles, into very close proximity with polyfluoroarenes
during the dynamic exchange process typical of micelles. This
effective binding of reactants along with hydrophobic effects
Reaction Optimization and Scope
Our investigation began with reaction of polyfluoroarene
1 with
bench-stable sodium arylsulfinate in various aqueous micellar
2
solutions (TPGS-750-M, SDS, FI-750-M, tween 20, pluronic F-
127, see Figure 2) using additives (NaF, NaCl, NaBr) to afford
product 3 (See SI). Optimization studies revealed a dependence
of the reaction on several variables; most notably, the presence
of aqueous nanomicelles of FI-750-M and sodium chloride as
well as acetone as an additive (Table 1). Additives are
presumably required to enhance the exchange process
between dynamic micelles. Notably, most reactions proceeded
cleanly at ambient temperature, i.e., 24–25 °C. No argon
atmosphere was required. FI-750-M was found to be superior
to any other surfactant. No desired reaction was observed when
neat water was used as a solvent. Sodium sulfinate salts
afforded clean reactions compared to their lithium counterparts
or the corresponding sulfinic acids.
After finding optimal reaction conditions (i.e., 10
equivalents sodium chloride and acetone as additives, sodium
sulfinate salt as coupling partner with an exact 1:1
stoichiometry of sulfinate salt to perfluoroarene, 3 wt%
aqueous FI-750-M as solvent; for details, see SI) the substrate
Table 1 Optimization of selective sulfonylation in nanomicelles
can
potentially
lead
to
clean
conversion
to
polyfluoroarylsulfones, especially when micellar reactant
concentration is high. Notably, the transformation involving
sulfinate salts are otherwise not possible in any polar-protic
solvents including water. Herein, we disclose a general,
efficient, mild, and sustainable method for the synthesis of
polyfluoroarlysulfones.
entry
micellar medium
additive
% yield 3
1
2
neat water
neat water
–
0
0*
1
NaCl
NaF
NaCl
NaF
NaCl
NaF
NaCl
3
3 wt% SDS
4
3 wt% SDS
1
5
3 wt% TPGS-750-M
3 wt% TPGS-750-M
3 wt% FI-750-M
3 wt% FI-750-M
3 wt% FI-750-M
3 wt% FI-750-M
3 wt% Tween 20
3 wt% Pluronic F-127
14
48
27
6
7
8
80 (100**)
†
9
–
57
38
52
26
10
11
12
NaBr
NaCl
NaCl
Conditions: 1 (0.5 mmol), 2 (0.6 mmol), additive (5 mmol), aqueous surfactant (0.8
mL), 0.2 mL acetone, rt, 4 h. Unless otherwise noted, yields are isolated. *18% yield
when 20% acetone was used as additional additive. **GCMS conversion. Prolonged
reaction time did not improve conversions. †in the absence of acetone.
scope was further established while paying attention to
functional group tolerance, sterics, and electronic parameters.
Remarkable generality was found with respect to the nature of
the sulfinate salt, which supports systems that are electronically
Figure 2 Surfactants evaluated in this study.
rich (Table 2; 10
3
,
5
,
6
,
, 21, 22, 26) and deficient (7, 8, 11, 12,
14 15 17 20, 25), containing aryl and heteroaryl combination
,
,
,
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reaction of 27 and
2
in a perfect 1:1 stoichiometry afforded
Table 2 Substrate scope of selective sulfonylation of polyfluoraromatics
clean product
9 in a quantitative yield within 2 hours. Although
micellar catalysis eliminates or drastically reduces organic
solvent in the reaction medium, the solvents are still utilized in
the process of product extraction and purification; this
remaining dependence is the basis for a common criticism of
Scheme 1 Reproducibility at gram-scale with no use of organic solvent for extraction
and purification—just simple filtration.
micellar catalysis. Therefore, technology needs to be developed
which does not require organic solvents for extraction and
product purification. A unique feature of FI-750-M is the
presence of optimal hydrophobicity in the micellar cores for
crystallization of sulfone products from the reaction mixture,
facilitating avoidance of solvent-intensive extraction and
purification processes. Accordingly, no organic solvent was
required for extraction of the gram-scale product. The product
was isolated with simple filtration and washing with water.
1
Notably, H NMR showed no residual surfactant in the product.
Aqueous nanomicelles recovered from this reaction were
further reused for substrate scope. Thus, neither aqueous nor
organic waste was generated in this process.
Conditions: polyfluoroaryl (0.25 mmol), sodium arylsulfinate (0.25 mmol), NaCl
(10 equiv.), 0.1 mL acetone, 0.4 mL 3 wt% aq. FI-750-M; *yields with reaction
temperature 45 oC; †lithium sulfinate salt was used.
(5, 7– , 17), cycloalkyl (21–23), and with considerable steric
10
26). Notably, the reactive chloro group on
polyfluoroarene ( 22) remained intact and did not show any
side reaction. No side reactions were observed at the 2’ and 6’-
position of pyridyl rings ( 11 13 14 22). Residues such as
acetyl (15 16), carbamate (23), ester (24), nitrile ( 20
21), formyl (25), and trifluoromethyl ( 12 17 19 26) are
well tolerated. No aldol-type product was observed when an
acetyl residue was present on a coupling partner. Good
reactivity was observed in substrates with notable steric
bulk
(
a
Scheme 2 Synthesis of polymer in micellar media—direct application of this
methodology. Conditions: 4 (0.28 mmol, 1.0 equiv.), 29 (0.56 mmol, 2.0 equiv.), 30
(0.84 mmol, 3.0 equiv.), K2CO3 (2.8 mmol, 10 equiv.), 10 mL 3 wt% aqueous FI-750-
M, reflux.
7–9,
7-
,
,
,
,
3
,
6
,
7
,
8,
,
As previously described, resulting sulfones are highly
applicable in material chemistry. One such application of these
4,
5
,
,
,
, 23,
compounds was demonstrated by a synthesis of polymer 31
which exhibits microporous properties facilitating separation of
trace impurities from gases (Scheme 2).19 Product
, which had
been obtained in 90% yield at gram scale, was subsequently
introduced into a polymerization reaction with 29 and 30
,
4
congestion (6, 26). Heteroaromatic thiophene (5) displayed
excellent reactivity without formation of any polymerized side
products. Percentage conversions to desired products were
mostly excellent. However, isolated yields ranged from
moderate to excellent depending upon the nature of substrates
and products (e.g., whether they are highly volatile or not).
Alternatively, reactions yields could be slightly improved by using
excess of sulfinate salt (See SI for details). However, in such cases,
product purifiation and extraction steps are required.
.
Resultant polymer 31 was obtained with high purity
quantitatively. Notably, this polymer synthesis was conducted
entirely in aqueous FI-750-M; unlike the previously reported
method, no organic solvent was used for its synthesis or
purification at any stage. Starting with octaflurotoluene and
sodium phenylsulfinate, a one-pot synthesis of 31 was also
achieved without affecting purity or yield.
For the most part, these micelle-enabled transformations
did not display any side reaction or double sulfonylation.
Therefore, no extra purification was required. Recycle studies
were also performed with a full recovery of additives and FI-
Implementation
Reproducibility and application of our experimental approach
was further verified by a gram scale reaction (Scheme 1). A
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Additional studies were undertaken to corroborate our
hypotheses about the nature of our reaction system. To better
understand experimental findings suggesting the beneficial
influence of additives on micelle size and size distribution, cryo-
TEM and dynamic light scattering (DLS) experiments were
conducted (Figure 3; for more details, see SI). Cryo-TEM in the
absence of any additive revealed the existence of round-shaped
nanomicelles of FI-750-M with sizes of 50–150 nm, and very
little agreegation of nanomicelles was observed. With 1 M NaCl
and 20% acetone as additives, aggregation of nanomicelles was
observed in cryo-TEM. Thus, the aggregation of nanomicelles
was a key factor that facilitated the exchange process as well as
close proximity of coupling partners. Notably, additives did not
cause any expansion of micelles. Similar results were obtained
in DLS studies. A wider distribution of nanomicelles was
detected in the absence of additive. With additives, a slight
increase in average diameter and narrowing of particle size
distribution was observed. The increase in micellar aggregation
along with reduction of peak area supports the hypothesis
behind the design of this reaction methodology.
Scheme 1 Demonstration of method greenness by E factor and recycle study.
Conditions: perfluoroarene (0.25 mmol), aryl sodium sulfinate (0.25 mmol), NaCl
(2.5 mmol, only in zeroth cycle), acetone (0.1 mL, only in zeroth cycle), 3 wt%
aqueous FI-750-M (0.4 mL, only in zeroth cycle), rt (unless otherwise noted), 6 h
(unless otherwise noted).
750-M between cycles (Scheme 3). Reuse of micellar reaction
media did not affect reaction outcomes in terms of yield or
reaction time. The polyfluoroarene was also varied in each
recycle and the outcome was similar to when a fresh solution of
FI-750-M was used. After obtaining 13 from the zeroth cycle by
simple filtration, the recovered aqueous solution of
nanomicelles and additives was reused for the first recycle to
obtain additional 13. Second, third, and fourth recycles were
performed with different substrates to obtain products
3 and
19. Notably, this is a clean process without generation of any
organic waste; i.e., E-factor = 0.7 Aqueous micellar media can
potentially be reused even beyond the fourth recycle.
Figure 4 Interfacial tension between water and FI-750-M surfactant as a function of
NaCl concentration in the water phase as predicted by DFT calculations.
Analytical and Computational Studies
Calculations using COSMO-RS21 revealed that the interfacial
tension (IFT) between the surfactant and water increased
significantly upon adding salt to the water (Figure 4). An
increased interfacial tension would lead to aggregation or
particle expansion in order to minimize the surface area, which
is consistent with Figure 2. Calculations with increasing amounts
of acetone showed that very little change in the IFT was
observed, which demonstrates that it was the addition of salt
that led to the increased aggregation. The IFT was negative for
low salt concentration, which is consistent with spontaneous
micelle formation for the pure FI-750-M surfactant. The
calculations also revealed that the proline linker was the most
hydrophilic part of the surfactant and thus responsible for
reducing the IFT. The water–surfactant interface would thus be
enriched with proline linker parts of the surfactant. The
lipophilic region would thus prefer to be located in the interior
Figure 3 Cryo-TEM and DLS results for 3 wt% FI-750-M with and without additives.
4 | Green Chem., 2017, 00, x-x | x
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Table 3 COSMO-RS predicted solubilities in 2.5 M NaCl solution and local regions of FI-
750-M and TPGS-750-M surfactants. All solubilities are written as log10(max mole
fraction) and thus represent the maximum attainable concentration in the phase. A value
of 0 represents complete solubility.
of the micelle according to the calculations while a portion of
mPEG and proline linker contribute to micellar interface.
However, the calculations do not take into account the full 3D
geometry and because the mPEG region is far larger than the
proline linker region, the interface between the micelles and the
surrounding water phase cannot be made up of only the proline
linker. Therefore, the mPEG region will undoubtedly also be in
contact with the surrounding water phase, but in such a way as
to maximize contact between the proline linker and the water.
solubility
of 1
-4.6
solubility
of 2
-0.3
solubility
of 1+2
-4.8
solution
2.5 M NaCl
TPGS-750-M
PEG region
-0.4
-1.2
-1.3
-5.7
-1.6
-2.0
-6.6
succinic acid linker -0.7
lipophilic part
FI-750-M
-0.9
PEG region
-0.4
-0.8
-1.3
-2.1
-0.2
-7.0
-2.5
-1.0
-8.3
proline linker
lipophilic part
In order to assess the influence of the salt additives, we also
calculated the partition coefficients for the sodium arylsulfinate 2
between water and the proline linker region as a function of the salt
chemistry (Table 4). The salt effectively pushes the sulfinate into the
micelles and increases local concentration in the proline linker. The
magnitude of the effect of different salt additives are NaCl = NaBr >
NaF > water, which are consistent with the experimental results (see
Table 1). These results confirm that the local concentration of
sulfinate salt in the micelle plays an important role for the reaction.
Table 4 Partition coefficients, log10(P) for Na-sulfinate (2) between salt solutions and the
FI-750-M proline linker region, predicted by COSMO-RS calculations. The more positive
the log(P) value, the more the Na-sulfinate (2) prefers the surfactant phase over the
aqueous solution.
Figure 3 FI-750-M molecular structure (top left), COSMO surface (top right) and
the partial COSMO surfaces (bottom row) of the surfactant regions defined in
Figure 1.
Experimental findings and proposed hypotheses were
further confirmed by gaining information about the local
solubility in FI-750-M. COSMO-RS local solubility predictions of
solution
log10(P)
-1.3
pure water
2.5 M NaF (aq)
2.5 M NaCl (aq)
2.5 M NaBr (aq)
-1.0
reactants
1 and 2 in water and the various parts of the FI-750-
-0.7
M surfactant revealed the importance of FI-750-M for this
synthetic methodology (Figure 4 and Table 3). Based on the
-0.7
calculations, perfluoroarene
1 is mainly located in the PEG
Therefore, the calculations demonstrate that, based on the local
predicted concentrations, FI-750-M is a better surfactant for the
reaction than TPGS-750-M as a result of the linker chemistry, which
is better at solubilizing the sodium aryl sulfinate in the former case.
The preferential location of proline linker at the micelle–water
interface could also play a role in the exchange process, with easy
access to sodium sulfinate from the water as well as polyfluoroarene
from the PEG region of the micelles.
region. Sulfinate salt prefers to be in either the water phase
2
or the proline linker region. On the logarithmic scale, the sum of
the logarithms represents a product of the maximum attainable
concentrations. A higher sum of solubilities means an increased
combined local concentration of the reactants, which
significantly increases the reaction rate. Clearly, in comparison
with TPGS-750-M, the maximum value is obtained for FI-750-M,
especially in the proline linker location (bold).
Conclusions
Proline-based surfactant FI-750-M has been shown to enable
clean and selective sulfonylation of polyfluoroarene in water
under mild conditions. The presented protocol uses easily
handled sulfinate salts, allows for recycling of the reaction
medium, and isolation of pure product by simple filtration; no
organic solvents are required for product extraction and
purification. The design concept behind FI-750-M was to mimic
polar-aprotic solvents by introducing a greater degree of
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10.1002/9780470988817.ch3, pp. 60-91; (j) S.-i. Shoda, H.
Uyama, J.-i. Kadokawa, S. Kimura and S. Kobayashi, Chem.
Rev., 2016, 116, 2307-2413; (k) A. Sakon, R. Ii, G. Hamasaka,
Y. Uozumi, T. Shinagawa, O. Shimomura, R. Nomura and A.
Ohtaka, Organometallics, 2017, 36, 1618-1622; (l) F. Iwasaki,
K. Suga, Y. Okamoto and H. Umakoshi, ACS Omega, 2017, 2,
91-97.
polarity into the micellar core, and the success of this approach
was demonstrated through empirical and theoretical
comparison with other surfactants. In particular, COSMO-RS
calculations indicated that the FI-750-M linker region was best
suited for mutual solubility of the polyfluoroarene and the
sulfinate anionic nucleophile. Protocol scalability and
application were demonstrated with gram-scale and polymer
syntheses.
3. (a) T. Kitanosono, M. Miyo and S. Kobayashi, ACS Sustainable
Chem. Eng., 2016, 4, 6101-6106; (b) J. O. Weston, H.
Miyamura, T. Yasukawa, D. Sutarma, C. A. Baker, P. K. Singh,
M. Bravo-Sanchez, N. Sano, P. J. Cumpson, Y. Ryabenkova, S.
Kobayashi and M. Conte, Catal. Sci. Technol., 2017, 7, 3985-
3998.
4. (a) L. Lempke, A. Ernst, F. Kahl, R. Weberskirch and N. Krause,
Adv. Synth. Catal., 2016, 358, 1491-1499; (b) S. R. K. Minkler,
N. A. Isley, D. J. Lippincott, N. Krause and B. H. Lipshutz, Org.
Lett., 2014, 16, 724-726; (c) N. Krause, Curr. Opin. Green
Sustainable Chem., 2017, 7, 18-22.
Conflicts of interest
The authors declare the following competing financial
interest(s): Patent is pending for surfactant(s) FI-750-M used in
the study.
5. (a) B. H. Lipshutz and S. Ghorai, Org. Lett., 2009, 11, 705-708;
(b) B. H. Lipshutz, D. W. Chung and B. Rich, Org. Lett., 2008,
10, 3793-3796; (c) B. H. Lipshutz, S. Ghorai, W. W. Y. Leong, B.
R. Taft and D. V. Krogstad, J. Org. Chem., 2011, 76, 5061-5073;
(d) B. H. Lipshutz, N. A. Isley, J. C. Fennewald and E. D. Slack,
Angew. Chem. Int. Ed., 2013, 52, 10952-10958; (e) B. H.
Lipshutz, S. Ghorai, A. R. Abela, R. Moser, T. Nishikata, C.
Duplais, A. Krasovskiy, R. D. Gaston and R. C. Gadwood, J. Org.
Chem., 2011, 76, 4379-4391; (f) S. G. Bruce H. Lipshutz,
Aldrichimica Acta, 2012, 45, 3-16; (g) B. H. Lipshutz, J. Org.
Chem., 2017, 82, 2806-2816.
6. (a) G. Hamasaka, T. Muto, Y. Andoh, K. Fujimoto, K. Kato, M.
Takata, S. Okazaki and Y. Uozumi, Chem. - Eur. J., 2017, 23,
1291-1298; (b) Y. M. A. Yamada, S. M. Sarkar and Y. Uozumi,
J. Am. Chem. Soc., 2012, 134, 3190-3198; (c) S. M. Sarkar, Y.
Uozumi and Y. M. A. Yamada, Angew. Chem. Int. Ed., 2011, 50,
9437-9441; (d) G. Hamasaka, T. Muto and Y. Uozumi, Angew.
Chem. Int. Ed., 2011, 50, 4876-4878.
Acknowledgment
This research work was supported in part by an award from
Kentucky Science and Engineering Foundation as per grant
agreement #KSEF-148-502-17-396 with the Kentucky Science
and Technology Corporation. We also acknowledge University
of Louisville and Novartis Pharma Basel for financial support.
GBH also acknowledges NSF (CHE-1401700) for financial
assistance. We also thank H. K. Nambiar for technical assistance.
High-resolution, accurate mass spectra were recorded by Ms.
Angela Hansen at the Indiana University Mass Spectrometry
Facility using a MAT-95XP mass spectrometer purchased with
NIH grant 1S10RR016657-01. We thank Dr. Aidan Taylor from
UCSB for obtaining cryo-TEM images.
7. (a) R. A. Sheldon, Green Chem., 2016, 18, 3180-3183; (b) R. A.
Sheldon, Green Chem., 2017, 19, 18-43; (c) R. A. Sheldon, J. R.
Soc., Interface, 2016, 13; (d) R. A. Sheldon, in Green
Notes and references
Biocatalysis, John Wiley
&
Sons, Inc, 2016, DOI:
1. (a) S. Handa, M. P. Andersson, F. Gallou, J. Reilly and B. H.
Lipshutz, Angew. Chem. Int. Ed., 2016, 55, 4914-4918; (b) S.
Handa, Y. Wang, F. Gallou and B. H. Lipshutz, Science, 2015,
349, 1087-1091; (c) P. Klumphu, C. Desfeux, Y. Zhang, S.
Handa, F. Gallou and B. H. Lipshutz, Chem. Sci., 2017, 8, 6354-
6358; (d) J. Brals, J. D. Smith, F. Ibrahim, F. Gallou and S.
Handa, ACS Catal., 2017, 7, 7245-7250; (e) A. Donner, K.
Hagedorn, L. Mattes, M. Drechsler and S. Polarz, Chem. - Eur.
J., 2017, 23, 18129-18133; (f) G. La Sorella, G. Strukul and A.
Scarso, Green Chem., 2015, 17, 644-683; (g) J. D. Smith, F.
Gallou and S. Handa, Johnson Matthey Technol. Rev., 2017,
61, 231-245.
10.1002/9781118828083.ch1, pp. 1-15; (e) R. A. Sheldon, ACS
Sustainable Chem. Eng., 2018, 6, 32-48; (f) R. A. Sheldon and
J. M. Woodley, Chem. Rev., 2018, 118, 801-838; (g) R. A.
Sheldon, Green Chem., 2014, 16, 950-963.
8. (a) S. Handa, J. C. Fennewald and B. H. Lipshutz, Angew. Chem.
Int. Ed., 2014, 53, 3432-3435; (b) M. Vashishtha, M. Mishra
and D. O. Shah, Appl. Catal., A, 2013, 466, 38-44; (c) N. R. Lee,
F. Gallou and B. H. Lipshutz, Org. Process Res. Dev., 2017, 21,
218-221; (d) N. A. Isley, R. T. H. Linstadt, S. M. Kelly, F. Gallou
and B. H. Lipshutz, Org. Lett., 2015, 17, 4734-4737; (e) X.
Zhang, G.-p. Lu and C. Cai, Green Chem., 2016, 18, 5580-5585.
9. (a) F. Terrier, in Modern Nucleophilic Aromatic Substitution,
2. (a) H. Renata, Z. J. Wang and F. H. Arnold, Angew. Chem. Int.
Ed., 2015, 54, 3351-3367; (b) J. Feng, S. Handa, F. Gallou and
B. H. Lipshutz, Angew. Chem. Int. Ed., 2016, 55, 8979-8983; (c)
C. M. Gabriel, M. Parmentier, C. Riegert, M. Lanz, S. Handa, B.
H. Lipshutz and F. Gallou, Org. Process Res. Dev., 2017, 21,
247-252; (d) M. Parmentier, C. M. Gabriel, P. Guo, N. A. Isley,
J. Zhou and F. Gallou, Curr. Opin. Green Sustainable Chem.,
2017, 7, 13-17; (e) B. Lipshutz, Curr. Opin. Green Sustainable
Chem., 2017, 7, A1-A3; (f) S. R. K. Minkler, B. H. Lipshutz and
N. Krause, Angew. Chem. Int. Ed., 2011, 50, 7820-7823; (g) C.
Varszegi, M. Ernst, F. van Laar, B. F. Sels, E. Schwab and D. E.
De Vos, Angew. Chem. Int. Ed., 2008, 47, 1477-1480; (h) K.
Manabe, Y. Mori, T. Wakabayashi, S. Nagayama and S.
Kobayashi, J. Am. Chem. Soc., 2000, 122, 7202-7207; (i) C.
Ogawa and S. Kobayashi, in Organic Reactions in Water,
Wiley-VCH Verlag GmbH
&
Co. KGaA, 2013, DOI:
10.1002/9783527656141.ch4, pp. 205-278; (b) C. N.
Neumann, J. M. Hooker and T. Ritter, Nature, 2016, 534, 369;
(c) E. Buncel, J. M. Dust and F. Terrier, Chem. Rev., 1995, 95,
2261-2280; (d) J. F. Bunnett and R. E. Zahler, Chem. Rev., 1951,
49, 273-412.
10. C. P. Ashcroft, P. J. Dunn, J. D. Hayler and A. S. Wells, Org.
Process Res. Dev., 2015, 19, 740-747.
11. (a) K. A. Bakeev, ed., Process Analytical Technology:
Spectroscopic Tools and Implementation Strategies for the
Chemical and Pharmaceutical Industries, John Wiley & Sons,
2010; (b) J. H. Clark and D. J. Macquarrie, eds., Handbook of
Green Chemistry and Technology, 2008; (c) C. Jiménez-
González and D. J. C. Constable, Green Chemistry and
Engineering: A Practical Design Approach, 2011; (d) J. M.
DeSimone, Science, 2002, 297, 799-803; (e) H. L. Leira, A.
Blackwell
Publishing
Ltd,
2007,
DOI:
6 | Green Chem., 2017, 00, x-x | x
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Page 8 of 8
View Article Online
DOI: 10.1039/C7GC03514D
Journal Name
COMMUNICATION
Tiltnse, K. Svendsen and L. Vetlesen, Contact Dermatitis, 1992,
27, 148-150; (f) D. J. C. Constable, C. Jimenez-Gonzalez and R.
K. Henderson, Org. Process Res. Dev., 2007, 11, 133-137.
12. Chemicals Listed Effective June 15, 2001 as Known to the State
to Cause Reproductive Toxicity: N-methylpyrrolidone,
California Environmental Protection Agency Office of
Environmental
Health
Hazard
Assessment,
https://oehha.ca.gov/media/downloads/proposition-
65/chemicals/61501not1.pdf, 2001.
13. L. Bergkamp and N. Herbatschek, Rev. Eur. Comp. Int. Environ.
Law, 2014, 23, 221-245.
14. O. Acevedo and W. L. Jorgensen, Org. Lett., 2004, 6, 2881-
2884.
15. (a) P. Robson, T. A. Smith, R. Stephens and J. C. Tatlow, J.
Chem. Soc., 1963, 3692-3703; (b) H. Amii and K. Uneyama,
Chem. Rev., 2009, 109, 2119-2183; (c) R. E. Banks, R. N.
Haszeldine, D. R. Karsa, F. E. Rickett and I. M. Young, J. Chem.
Soc. C, 1969, 1660-1662.
16. S. Bhunia, G. G. Pawar, S. V. Kumar, Y. Jiang and D. Ma, Angew.
Chem. Int. Ed., 2017, 56, 16136-16179.
17. A. Darehkordi, M. Ramezani, F. Rahmani and M. Ramezani, J.
Heterocycl. Chem., 2016, 53, 89-94.
18. G. Zhou, C.-L. Ho, W.-Y. Wong, Q. Wang, D. Ma, L. Wang, Z.
Lin, T. B. Marder and A. Beeby, Adv. Funct. Mater., 2008, 18,
499-511.
19. (a) N. Du, G. P. Robertson, J. Song, I. Pinnau, S. Thomas and M.
D. Guiver, Macromolecules, 2008, 41, 9656-9662; (b) F.-M.
Hsu, C.-H. Chien, Y.-J. Hsieh, C.-H. Wu, C.-F. Shu, S.-W. Liu and
C.-T. Chen, J. Mater. Chem., 2009, 19, 8002-8008.
20. Unpublished results.
21. (a) A. Klamt, F. Eckert and W. Arlt, Annu. Rev. Chem. Biomol.
Eng., 2010, 1, 101-122; (b) M. P. Andersson, M. V. Bennetzen,
A. Klamt and S. L. S. Stipp, J. Chem. Theory Comput., 2014, 10,
3401-3408.
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