Task-specific ionic liquid incorporating anionic heteropolyacid-catalyzed Hantzsch and Mannich multicomponent reactions. Ionic liquid effect probed by ESI-MS(/MS)

Article abstract of DOI:10.1016/j.tet.2013.10.033

A task-specific ionic liquid with a Bronsted acid (1-(3-sulfopropyl)-3- methylimidazolium hydrogen sulfate, namely MSI) bearing an anionic heteropolyacid derivative ([PW₁₂O₄₀]^3-, namely PW) were used as an efficient catalyst for the three-component Mannich and Hantzsch reactions. Using (MSI)₃PW as the catalyst supported in imidazolium-based ionic liquids allowed these multicomponent reactions to take place in good to excellent yields. The Mannich reaction, performed at room temperature, was also evaluated by means of electrospray (tandem) mass spectrometry - ESI-MS(/MS). ESI-MS data pointed to the origin of the ionic liquid effect, i.e., formation of ion pairs with the charged reaction intermediates and furthers association into larger supramolecular aggregates. DFT calculations revealed the strength of the supramolecular interactions between the charged species detected by ESI-MS and the spontaneity association of these ion pairs affording larger supramolecular aggregates.

Full text of DOI:10.1016/j.tet.2013.10.033

Tetrahedron 70 (2014) 3306e3313
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Task-specific ionic liquid incorporating anionic heteropolyacid-
catalyzed Hantzsch and Mannich multicomponent reactions. Ionic
liquid effect probed by ESI-MS(/MS)
Haline G.O. Alvim a, Giovana A. Bataglion b, Luciana M. Ramos a, Aline L. de Oliveira a,
,
Heibbe C.B. de Oliveira a, Marcos N. Eberlin b, Julio L. de Macedo c, Wender A. da Silva d
*
,
Brenno A.D. Neto a
,
*
a Laboratory of Medicinal and Technological Chemistry, University of Brasilia (IQ-UnB), Campus Universitario Darcy Ribeiro, CEP 70904970, P.O. Box
4478, Brasilia-DF, Brazil
b ThoMSon Mass Spectrometry Laboratory, University of Campinas-UNICAMP, Campinas SP 13085-970, Brazil
c Laboratory of Catalysis, Institute of Chemistry, University of Brasília, P.O. Box 4478, CEP 70904970 Brasília, DF, Brasil
d Laboratory for Bioactive Compounds Synthesis, University of Brasilia (IQ-UnB), Campus Universitario Darcy Ribeiro, CEP 70904970, P.O. Box 4478,
Brasilia-DF, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 August 2013
Received in revised form 7 October 2013
Accepted 11 October 2013
Available online 18 October 2013
A task-specific ionic liquid with a Bronsted acid (1-(3-sulfopropyl)-3-methylimidazolium hydrogen
sulfate, namely MSI) bearing an anionic heteropolyacid derivative ([PW12O40]
3ꢀ, namely PW) were used
as an efficient catalyst for the three-component Mannich and Hantzsch reactions. Using (MSI)3PW as the
catalyst supported in imidazolium-based ionic liquids allowed these multicomponent reactions to take
place in good to excellent yields. The Mannich reaction, performed at room temperature, was also
evaluated by means of electrospray (tandem) mass spectrometrydESI-MS(/MS). ESI-MS data pointed to
the origin of the ionic liquid effect, i.e., formation of ion pairs with the charged reaction intermediates
and furthers association into larger supramolecular aggregates. DFT calculations revealed the strength of
the supramolecular interactions between the charged species detected by ESI-MS and the spontaneity
association of these ion pairs affording larger supramolecular aggregates.
Keywords:
Ionic liquids
Multicomponent reactions
Mechanism
ESI-MS
Ó 2013 Elsevier Ltd. All rights reserved.
Bioactive
1. Introduction
Ionic liquids (IL), especially those based on the imidazolium
cation16e18 (Fig. 1), have been applied as supporters for catalysts
Multicomponent reactions (MCR) are useful tools in organic
synthesis1e3 giving direct, elegant, and simple access to bioactive
compounds libraries.4e6 Multi-reagents brought together in a one-
pot version is a very attractive protocol, especially from the view-
point of eco-friendly and sustainable conditions,7 but still suffers
from many drawbacks, as already reviewed.8e10 Long reaction
times, harsh reaction conditions, reagents excesses, high temper-
atures, toxic solvents, expensive catalysts, demanding purification,
and low yields are major limitations of MCR. Catalysis occupies
and/or as reaction media for many organic transformations that are
difficult to occur or are inefficient in classical organic solvents.19e21
IL are, definitely, a major class of exceptional ionic fluids used as
solvents for synthesis and catalysis.22e24 IL are already successfully
used in the chemical industry25 and a likely possible way to envi-
ronmental acceptability.26
R1 = Me; R2 = Bu; X = BF4 = BMI.BF4
n
R1 = Me; R2 = Bu; X = PF6 = BMI.PF6
n
+
N
N
R1
R2
therefore
a central role toward the development of more
R1 = Me; R2 = Bu; X = NTf2 = BMI.NTf2
n
environmentally-friend and efficient MCR conditions aiming at
better yields, selectivities, and atom economy;11e15 i.e. highly de-
sired features for green chemistry progress.
_
X
Fig. 1. 1,3-Dialkylimidazolium-based ionic liquids commonly used in homogeneous or
heterogeneous catalysis.
The combination of MCR with IL (for catalyzed reactions) has been
regarded as ‘a perfect synergy for eco-compatible heterocyclic syn-
thesis’, as ‘a promising strategy for the development of valuable eco-
* Corresponding authors. Tel.: þ55 61 31073867; fax: þ55 61 31073901
(B.A.D.N.); tel.: þ55 61 31073860 (W.A.S.); e-mail addresses: wender@unb.br (W.A.
da Silva), brenno.ipi@gmail.com (B.A.D. Neto).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.10.033

H.G.O. Alvim et al. / Tetrahedron 70 (2014) 3306e3313
3307
compatible organic synthesis procedures’ and, finally, as ‘an excellent
media for multiple bond-forming transformations’.27 IL have already
proved to be outstanding media for MCR.27e29 The promising com-
bination of MCR and IL (catalyzed reactions) is just beginning to be
explored and still there are much to be achieved. Task-specific ionic
liquids (TSIL) have also been successfully employed as alternative
acid30 and basic31 catalysts to perform MCR. Since it is possible to
diversely functionalize the anion or the cation (or both) to tailor
a TSIL, it is reasonable to envisage specific interactions and properties
aiming at improved catalytic conditions due to the presence of those
tags tethered to the structure of the catalyst.32e35
Considering the likely advantages of using IL (and/or TSIL) under
catalytic conditions to promote MCR, we have demonstrated the
synergic effect of a copper (pre)catalyst and the anionic moiety of
BMI$PF6 to the formation and stabilization of key reactive in-
termediates in the multicomponent Biginelli reaction.36 In another
recent study, we successfully tested a new iron-containing TSIL as
a catalyst of dual activation mode to obtain a library of bioactive
dihydropyrimidinones from an MCR.37 More recently, we have
analyzed and compared the use of a TSIL incorporating anionic
heteropolyacid derivative (Scheme 1) as the catalyst for the three-
component Biginelli reaction under homogeneous (Scheme 1) and
heterogeneous conditions.38
BMI$NTf2. MSI3PW was synthesized and characterized as described
elsewhere.38,42 Briefly, the zwitterionic species (see Scheme 1) is
treated with H3PW12O40 (HPWdphosphotungstic acid) affording
the desired catalyst in quantitative yields with the heteropolyacid
derivative as the counteranion ([PW12O40] , namely
3ꢀhPW3ꢀ
herein as PW).
Hantzsch reaction
R1
O
O
O
NH4X
+
R3 (DHP)
R1
R3
H
O
O
R2
R2
N
H
+
R2
R3
Mannich reaction
R2
R1
H
O
O
O
N
R2
NH2
+
+
R1
R3
H
R3
(BAK)
Scheme 2. Hantzsch and Mannich three-component reactions performed using
MSI3PW as the catalyst under homogeneous conditions and BMI$NTf2 as the ionic
media.
-
SO3
+
SO3H
N
N
H3PW12O40
H2O:MeOH
Aiming at the synthesis of some 1,4-dihydropyridines (DHP), we
initially tested the Hantzsch43e45 reaction applying the best cata-
lytic conditions previously developed for MCR using MSI3PW as the
catalyst,38 i.e., 90 ꢁC, 4 h of reaction and 5 mol % of the catalyst
supported in BMI$NTf2. DHP has been found to exhibit beneficial
biological effects, such as that for cardiovascular diseases acting as
calcium channel blockers.46 The Hantzsch reaction catalyzed by
MSI3PW yielded DHP in good to excellent yields (Table 1). Am-
monium acetate may be replaced by ammonium chloride but
a slight overall reduction in yields (w5e8%) was noted.
3
N
N
3-
[PW12O40
]
MSI3PW
Biginelli reaction
(homegeneous catalysis)
R1
O
X
O
H
X
+
R3
N
R1
MSI3PW
H2N
NH2
H
Table 1
BMI.NTf2
R2
N
H
O
O
Hantzsch reaction catalyzed by MSI3PW (5 mol %) at 90 ꢁC for 4 h in BMI$NTf2
(homogeneous system)
+
R2
R3
R1
O
O
Dihydropyrimidinone
O
O
O
R3
R3
Scheme 1. Synthesis of the Bronsted acid task-specific ionic liquid (MSI cation) with
anionic heteropolyacid derivative ([PW12O40]
3ꢀ, PW anion) applied as the catalyst
NH OAc
+
+
4
R1
(MSI3PW) for the Biginelli reaction.38
R2
R3
H
R2
R2
N
H
In the example depicted in Scheme 1,38 equimolar quantities of
the three components could be used. The catalyst also showed to be
highly active in BMI$NTf2, whereas those reactions carried out in
BMI$BF4 or BMI$PF6 lead to reagent decomposition and lower
yields. Under the best developed condition, the Biginelli adduct
could be obtained in quantitative yields in just a few hours and the
system could be recycled. Due to our interest in MCR and catalytic
reactions conducted in IL,39e41 we investigate the use of MSI3PW
for Hantzsch and Mannich MCR and report herein that it function as
a very active catalyst with impressive IL effect. We also evaluated
the IL effect, via ion-pairing and larger supramolecular aggregates,
by electrospray ionization (tandem) mass spectrometry ESI-MS(/
MS) and DFT calculations.
Entry
R1
Ph
3-OHePh
H
R2
R3
Yield (%)
DHP
1
2
3
CH3
CH3
CH3
CH3CH2O
CH3CH2O
CH3CH2O
99
87
84
DHP(a)
DHP(b)
DHP(c)
O
O
O
O
4
5
98
98
DHP(d)
DHP(e)
O
O
Ph
2. Results and discussion
Another advantage of our protocol was that no reagent
excess was required to perform the Hantzsch MCR, and four bio-
active DHP(aec,e),47e49 used as antioxidants, antimicrobial,
The three-component Hantzsch and Mannich reactions
(Scheme 2) were conducted using MSI3PW as the catalyst in

3308
H.G.O. Alvim et al. / Tetrahedron 70 (2014) 3306e3313
anticoagulant, and channel blockers were directly synthesized in
good to excellent yields (84e99%).
ESI(þ)-MS, only the TSIL cation MSI (m/z 205) could be detected
and its ESI(þ)-MS/MS was acquired (Fig. 2B).
Having verified the excellent catalytic activity of MSI3PW, we
tested it to promote another three-component reaction, i.e., the
Mannich reaction (Scheme 2), but now at conditions close to room
temperature. Note that this reaction has been found to be very
sensitive to temperature and Mannich50e52 adducts (
b-amino car-
bonyl compounds, BAK) are often thermo-unstable. Side reactions
and decompositions of both reagents and products are normally
favored with increased temperatures; therefore low temperatures
are normally applied for this MCR.53e55 More efficient Mannich
reactions would be highly desirable since this MCR provides direct
and simple access to
b-amino carbonyls (Scheme 2), which are
units found in many natural and synthetic products of pronounced
biological activities.56 All Mannich reactions (Table 2) were there-
fore conducted using equimolar quantities of the reagents at 30 ꢁC.
Note in Table 2 that fortunately all Mannich products were
synthesized in good to excellent yields (75e98%) at just 30 ꢁC and
again with no reagent excess. Some of the BAK showed to be highly
unstable after isolation (see NMR spectra in the Supplementary
data file to note the degradation), but unstable BAK can be iso-
lated and immediately used as synthetic intermediates,57e60 as
reviewed elsewhere.61
Table 2
Mannich reaction catalyzed by MSI3PW (5 mol %) at 30 ꢁC in BMI$NTf2
R2
H
O
O
O
N
R2
NH2
+
+
R1
R3
H
R3
R1
Entry
R1
R2
R3
Yield (%)
BAK
1
2
3
4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-OHePh
95
85
98
75
BAK(a)
BAK(b)
BAK(c)
BAK(d)
4-NH2ePh
4-PheNO2
4-PheNH2
O
O
5
4-PheNO2
Ph
80
BAK(e)
Fig. 2. (A) ESI(ꢀ)-MS of the methanolic solution of the MSI3PW catalyst. MSI is the
3ꢀ
SO3H functionalized imidazolium cation derivative (m/z 205) and PW is [PW12O40
(B) ESI(þ)-MS/MS of the MSI cation.
]
.
Since the Mannich reaction was efficiently performed under
amenable conditions, we decided to investigate via ESI-MS(/MS) its
mechanism as well as the IL effect over this MCR. ESI-MS is known
for its efficient and accurate analysis of reaction solution compo-
nents because of its capability of fast and sensitive ‘fishing’ of ionic
reaction partners from solution directly to the gas phase as un-
disturbed ‘cold’ ions; therefore acting as a proper bridge connecting
solution and gas phase chemistries.62 Investigations of reaction
mechanisms is one of the beauties of the Nobel laureate ESI-MS
technique, which is capable of providing continuous snapshots of
the reaction solution, hence allowing the online interception and
characterization of reaction intermediates and of their appearance
and fading63e65 (including transient species66), hence the dynamic
ionic changes67 during the whole reaction time period.68
Initially, the MSI3PW catalyst was characterized in both the
positive and negative ion modes, i.e., via ESI(ꢀ)-MS and ESI(þ)-MS.
ESI(ꢀ)-MS (Fig. 2A) revealed the triply charged PW3ꢀ as the most
abundant ion (methanolic solution) followed by [PWþH]2ꢀ. Note
that no doubly protonated ion [PWþ2H]ꢀ could be detected;
therefore indicating proper dissociation of the Bronsted acid moi-
ety. Interestingly, doubly charged ion [PWþMSI]2ꢀ was also
detected due to the supramolecular association of MSI cation with
PW3ꢀ anion. This association of cations and anions (supramolecu-
lar) is common in the chemistry of IL and TSIL derivatives.69 For
After, the MSI3PW catalyst was also subjected to ESI(ꢀ)-MS
(Fig. 3) now in the presence of the IL (BMI$NTF2).
Note in Fig. 3 that the [PWþMSI]2ꢀ anion could not be detected.
Instead, the detection of [PWþBMI]2ꢀ anion revealed that in the
presence of the IL, the cation BMI efficiently replaces the cation
MSI. The ESI(ꢀ)-MS of Fig. 3 also shows the detection of the
monoprotonated [PWþH]2ꢀ anion, but at a reduced abundance as
compared to Fig. 2, in accordance with the expected acidic strength
increase in the IL media. It has been already demonstrated that
Bronsted acids (and Bronsted acids TSIL) can behave as superacids
when supported (or embedded) in IL.70,71 The ESI-MS data obtained
for the MSI3PW catalyst in the presence of BMI$NTf2 is therefore in
accordance with this predictable behavior, that is, [PWþH]2ꢀ had
its abundance significantly diminished indicating the dissociation
of the acid was even at a larger extent; i.e., a more effective acid
strength of the catalyst because of both the additional interactions
found in the ionic fluid and the consequent stabilizing effects as-
sociated with these supramolecular interactions.
After the catalyst characterization, we first monitored by ESI(þ)-
MS the Mannich reaction to investigate the possible intervention of
the IL (BMI$NTF2) forming supramolecular ionic species. The

H.G.O. Alvim et al. / Tetrahedron 70 (2014) 3306e3313
3309
Fig. 3. ESI(ꢀ)-MS of the methanolic solution of the MSI3PW catalyst in the presence of
BMI$NTf2. BMI is 1-n-buthyl-3-methyl imidazolium cation derivative (m/z 139), PW is
Fig. 5. ESI(þ)-MS/MS of the Mannich adduct of m/z 302.
ꢀ
3ꢀ
and NTf2 (see the inset) is the bis(trifluoromethane)sulfonamide anion
[PW12O40
]
(m/z 280).
Two important supramolecular ions of m/z 644 and m/z 601
were also detected and characterized by ESI(þ)-MS/MS (Figs. 6 and
7). This result demonstrates the intervention of the IL components
in the formation and stabilization of the charged intermediates of
the Mannich reaction.
reaction mixture of aniline, benzaldehyde, and acetophenone, in
the presence of BMI$NTF2 and MSI3PW was therefore monitored
(Fig. 4).
Fig. 6. ESI(þ)-MS/MS of the supramolecular ion of m/z 644.
Fig. 4. ESI(þ)-MS of the Mannich reaction solution catalyzed by MSI3PW in the
presence of BMI$NTf2.
Fortunately, sevꢀeral cationic intermediates and supramolecular
cations with NTf2 association could be detected and properly
characterized by ESI(þ)-MS/MS. Importantly, before the iminium
ion formation (the first step of the mechanism of the Mannich re-
action) no other intermediate (or the Mannich adduct) associated
with this MCR could be detected. This result indicates that the
limiting step of the reaction is indeed the formation of the iminium
ion, which could be detected only after an overnight monitoring at
30 ꢁC. A pre-formed iminium ion (a white solid formed upon
heating pure aniline with pure benzaldehyde) was also used with
similar results. Before the appearance of the iminium ion of m/z
182, only the protonated aniline (m/z 94), the protonated aceto-
phenone (m/z 121), the MSI cation (m/z 205), and the BMI cation
(m/z 139) could be detected. After its appearance, however, the
protonated Mannich adduct of m/z 302 was detected and subjected
to ESI(þ)-MS/MS (Fig. 5).
Fig. 7. ESI(þ)-MS/MS of the supramolecular ion of m/z 601. Note the neutral loss of
[iminium$NTf2] is favored when compared with the neutral loss of BMI$NTf2.

3310
H.G.O. Alvim et al. / Tetrahedron 70 (2014) 3306e3313
In the supramolecular ion of m/z 644, the NTf2ꢀ anion (m/z 280)
Other key supramolecular aggregate of m/z 601 (Fig. 7), corre-
sponding to the ion pair BMI$NTf2 associated with the key iminium
ion intermediate, could also be properly intercepted and charac-
terized. Note the loss of the neutral ion pair [iminium ion$NTf2] that
affords BMI cation of m/z 139, as well as the loss of BMI$NTf2 that
affords the iminium ion of m/z 182. The preferential neutral loss of
[iminium ion$NTf2] revealed that the intrinsic relative strength of
coordination is [iminium ion$NTf2]>BMI$NTf2.
Based on the data obtained by ESI-MS(/MS) and the importance
of the IL effect for the Mannich reaction, a catalytic cycle proposi-
tion could be formulated including the ion-pairing effect (Scheme
3). Note that larger IL supramolecular aggregates may also take
place.
The equilibrium between BMI$NTf2 and MSI3PW revealed by
ESI-MS monitoring shows that the MSI cation is extensively or to-
tally replaced by the BꢀMI cation in associations with the PW3ꢀ
anion (Scheme 3). NTf2 is known to be an anion of very low co-
ordination strength74 therefore the cation MSI is more available
and likely therefore the acidic hydrogen dissociation occurs at
a larger extension. The aldehyde is then protonated and the amine
addition, affording the key iminium intermediate, takes place. The
iminium ion, as a charged intermediate, is capable of forming ion
was found associated with two iminium cations (of m/z 182),
ꢀ
whereas in the supramolecular ion of m/z 601, the NTf2 is asso-
ciated with both an iminium ion (of m/z 182) and a BMI cation (of
m/z 139). Note that all ESI-MS were carried out from methanolic
solutions, and that this polar and protic solvent favors the disso-
ciation of those supramolecular species, in accordance with pre-
vious results.72 Likely therefore, the high stability of the two
supramolecular aggregates of m/z 644 and m/z 601 allowed their
detection and characterization by ESI(þ)-MS/MS (Figs. 6 and 7)
despite the methanolic solutions.
The supramolecular aggregate characterized in Fig. 6 shows
that indeed ion-pairing is a key factor in the reaction sol-
ution media. This stabilizing effect of the IL cations and anions,
favoring the formation and stabilization of charged (or polar)
intermediates (or transition states) via both ion-pairing and larger
supramolecular aggregates, is known as the IL effect.16,17 As re-
cently reviewed,73 ESI-MS has been an excellent tool to detect and
characterize these IL supramolecular aggregates. The detection
ꢀ
of aggregates of the NTf2 anion with the key iminium ion in-
termediate therefore points firmly to a positive IL effect over the
Mannich reaction.
Scheme 3. Mannich three-component catalytic cycle with ionic liquid effect (left). Note the equilibrium between MSI3PW and BMI$NTf2ꢀrevealed by ESI-MS monitoring. The
charged cationic intermediates (e.g., iminium ion) from the Mannich reaction can afford supramolecular aggregates (and ion pairs) with NTf2 anion. Most of the structures shown
in the catalytic cycle were detected and characterized by ESI-MS(/MS) (right).

H.G.O. Alvim et al. / Tetrahedron 70 (2014) 3306e3313
3311
ꢀ
pairs with NTf2 anion (as noted by the MS experiments) and also
to associate affording larger supramolecular aggregates. Upon ag-
gregation, additional stabilizing effects are expected. Finally, the
addition to the iminium ion takes place followed by product release
and restoration of the acidic catalyst.
In order to gain insight as to the importance of the IL effect in the
stabilization of the charged intermediates in the Mannich MCR,
theoretical calculations (DFT) were also performed. The DFT in-
vestigations were centered on the key supramolecular in-
termediate of m/z 601 (Fig. 7) intercepted and characterized by ESI-
MS(/MS). All structures had their geometries fully optimized at
B3LYP/6-31þG(d,p) level of theory and single point performed at
M062X/6-311þþG(2d,2p) level of calculations. After optimization,
the thermodynamics properties for the dissociations of the two
observed ion pairs (neutral loss) i.e. via [iminium ion$NTf2] or
BMI$NTf2 loss from the supramolecular ion of m/z 601 (Fig. 8) were
calculated.
The threshold energy (DH) required to dissociate the iminium
ion intermediate from the supramolecular structure (i.e., neutral
loss of BMI$NTf2) is considerably higher than that to remove the
imidazolium ion (i.e., neutral loss of [iminium ion$NTf2]), therefore
Fig. 9. Relative energy profile for the formation of the supramolecular aggregate
{[iminium ion$NTf2]þ[BMI$NTf2]} at the M062X/6-311þþG(2d,2p)//B3LYP/6-
31þG(d,p) level of calculation.
possible to detect and characterize key supramolecular aggregates
pointing to the positive effect of the IL over the Mannich reaction in
the formation and stabilization of charged intermediates, particu-
larly the key iminium ion intermediate. DFT calculations showed
how pronounced is the IL effect to facilitate the formation and
stabilization of the this key intermediate (rate-limiting step) as well
as the other charged intermediates trough both ion-pairing and the
formation of larger supramolecular aggregates.
3. Experimental section
3.1. General
Chemicals and solvents were purchased from commercial
sources. Liquid reagents and solvents were distilled prior to be
used. ESI-MS and ESI-MS/MS measurements were performed in the
positive ion mode (m/z 50e2000 range) on an HDMS instrument.
This instrument has a hybrid quadrupole/ion mobility/orthogonal
acceleration time-of-flight (oa-TOF) geometry and was used in the
TOF Vþ mode. All samples were dissolved in methanol to form
100
m
M solutions and were directly infused into the ESI source at
a flow rate of 15
m
L/min after 18 h at 30 ꢁC. ESI source conditions
were as follows: capillary voltage 3.0 kV, sample cone 20 V, ex-
traction cone 3 V. NMR spectra were recorded on a 7.05 T in-
strument using a 5-mm internal diameter probe operating at
300 MHz for 1H and at 75 MHz for 13C. Chemical shifts were
expressed in parts per million (ppm) and referenced by the signals
of the residual hydrogen atoms of the deuterated solvent (CDCl3 or
DMSO-d6), as indicated in the legends. All electronic structure
calculation performed in this work were performed within
KohneSham Density Functional Theory (DFT) formalism.75,76 The
geometry optimizations were carried out using the B3LYP/6-
31þG(d,p) level of calculation. At the same level of theory, the
fundamental vibrational frequency calculations were carried out to
ensure the true minima, to compute zero-point vibrational energy
(ZPVE) and to derive the thermochemical corrections for the heat of
formation, Gibbs free energy, and the binding energy. The calcu-
lated frequencies were scaled by a factor of 0.9642 and the ZPVE
and thermodynamic functions were calculated at 298.15 K and
1 atm. The optimized geometries were used for the single point
calculation at M062X/6-311þþg(2d,2p) level of calculation. The
M062X meta exchange-correlation functional is recommend for
Fig. 8. Thermodynamic for the two observed ion pairs dissociations from the supra-
molecular ion of m/z 601. (Left) Neutral loss of [iminium ion$NTf2]. (Right) Neutral loss
of BMI$NTf2. Calculations at M062X/6-311þþG(2d,2p)//B3LYP/6-31þG(d,p) level of
theory.
in accordance with the results obtained from the ESI-MS/MS ex-
periments (Fig. 7).
Finally, we calculated the IL effect via the formation of a supra-
molecular aggregate of two ion pairs, i.e., {[iminium ion$NTf2]þ
[BMI$NTf2]} (Fig. 9), which was found to be associated with a DG of
ꢀ2.53Kcalmolꢀ1
(
D
H¼ꢀ12.01 Kcal molꢀ1
;
D
S¼ꢀ31.79calmolꢀ1 Kꢀ1
)
hence spontaneous and energetically favored.
In summary, we have demonstrated that the TSIL MSI3PW
functions as a very efficient catalyst for the Hantzsch and Mannich
MCR to obtain bioactive compounds in excellent yields. ESI-MS(/
MS) investigations allowed a better comprehension on the in-
tervention of supramolecular species on the mechanism of the
Mannich MCR with the IL components. By ESI-MS(/MS) it was

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H.G.O. Alvim et al. / Tetrahedron 70 (2014) 3306e3313
applications involving main-group thermochemistry, kinetics, non-
covalent interactions, and electronic excitation energies to valence
and Rydberg states.77 To avoid a basis-set superposition error
(BSSE) the thermodynamics properties and bind energies were
counter-poise corrected using a standard approach by Boys and
Bernardi.78 All theoretical calculations were carried out using
Gaussian 09 program suite.79
149.3, 148.2, 134.8, 128.6, 122.8, 121.3, 111.1, 104.9, 60.1, 50.6, 40.8,
36.9, 32.7, 29.4, 27.0, 19.4, 14.1, and 11.9.
3.3.5. 3,4,6,7,9,10-Hexahydro-3,3,6,6-tetramethyl-9-phenyl-
1,8(2H,5H)-acridinedionedDHP(e). 1H NMR (300 MHz DMSO-d6
and
d in ppm) 1.01 (12H, s, Me), 2.07 (4H, s, CH2), 2.30 (4H, s,
CH2CO), 4.26 (1H, s, CH), 5.93 (1H, s, NH) e 7.47e6.92 (5H, m, Ph).
13C NMR (75 MHz, DMSO-d6) 206.4, 196.5, 187.7, 163.3, 141.5, 128.3,
126.8, 114.8, 47.0, 31.8, and 28.2.
The known MSI cation80 was synthesized as it follows: to a so-
lution of 1,3-propanesultone (20 mmol) dissolved in toluene
(100 mL) is added 1-methylimidazole (20 mmol). The solution is
allowed to react at 100 ꢁC for 24 h and the white zwitterionic solid
formed is washed with ethyl acetate, filtrated, and dried in vacuum.
The known MSI3PW42 is prepared by treating the zwitterionic solid
(15 mmol) with HPW (5 mmol) in 30 mL of water/methanol (1:1) at
50 ꢁC for 24 h. After, the solvent is concentrated under vacuum and
a white solid precipitates. The solid is washed with ethyl ether and
dried in vacuum affording the desired product in quantitative yield.
3.3.6. 3-Diphenyl-3-(phenylamino)-1-propanonedBAK(a). 1H NMR
(300 MHz CDCl3 and
d in ppm) 3.41(1H, dd, J 16.0, 7.3 Hz, CHaHb),
3.51 (1H, dd, J 16.0, 5.5 Hz, CHaHb), 5.00 (1H, dd, J 7.3, 5.5 Hz, CH),
6.56 (2H, m, Ph), 6.65 (1H, m, Ph), 7.23 (1H, m, Ph), 7.31 (2H, t, J
7.5 Hz, Ph), 7.47e7.42 (2H, m, Ph), 7.46 (4H, m, Ph), 7.56 (1H, t, J
7.5 Hz, Ph), 7.91 (2H, d, J 6.0 Hz, Ph). 13C NMR (75 MHz, CDCl3) 198.7,
146.9, 142.9, 136.6, 133.4, 129.1, 128.8, 128.2, 126.3, 117.7, 113.8, 54.7,
46.3.
3.2. General procedure for the Hantzsch reaction
3.3.7. 3-[(4-Aminophenyl)amino]-1,3-diphenylpropan-1-
onedBAK(b). 1H NMR (300 MHz CDCl3 and
d in ppm): 3.50 (d, J
A sealed Schlenk tube containing 0.5 mL of BMI$NTf2, 1.00 mmol
of the aldehyde, 2.00 mmol of the 1,3-dicarbonyl compound, 1.00 of
NH4OAc, and MSI3PW (5 mol %) was allowed to react at 90 ꢁC for
4 h. Substrates were purified by chromatographic column eluted
with mixtures of hexane/ethyl acetate or, whether the product
precipitates in the reaction medium, it is filtered and washed with
cold ethanol.
6.0 Hz, CH2), 5.03 (q, J 6.0 Hz, CH), 6.60 (m, Ph), 7.11 (m, Ph),
7.19e7.62 (m, Ph), 7.80e7.95 (m, Ph). 13C NMR (75 MHz, CDCl3):
196.6, 189.7, 141.6, 133.3, 130.6, 129.3, 128.8, 128.6, 124.7, 124.6,
122.4, 118.8, 113.8, 54.0, and 45.8. This compound was very
unstable.
3 . 3 . 8 . 3 - [ ( 4 - N i t r o p h e n y l ) a m i n o ] - 1, 3 - d i p h e n y l - 1 -
propanonedBAK(c). 1H NMR (300 MHz CDCl3 and
d in ppm) 3.52
(2H, d, J 6.0 Hz, CH2), 5.10 (1H, q, J 6.0 Hz, CH), 5.56 (1H, d, J 6.0 Hz,
NH), 6.51 (2H, m, Ph), 7.26e7.62 (8H, m, Ph), 7.88 (2H, m, Ph), 8.00
(2H, m, Ph). 13C NMR (75 MHz, CDCl3) 196.6, 189.7, 141.6, 133.3,
130.6, 129.3, 128.8, 128.6, 124.7, 124.6, 122.4, 118.8, 113.8, 54.0, and
45.8.
3.3. General procedure for the Hantzsch reaction
A sealed Schlenk tube containing 0.5 mL of BMI$NTf2, 1.00 mmol
of the aldehyde, 1.00 mmol of the amine, and 1.00 mmol of the
ketone and MSI3PW (5 mol %) was allowed to react at 30 ꢁC for 20 h.
Substrates were purified by chromatographic column eluted with
mixtures of hexane/ethyl acetate.
3.3.9. 3-[(4-Aminophenyl)amino]-1-(4-hydroxyphenyl)-3-
phenylpropan-1-onedBAK(d). 1H NMR (300 MHz DMSO-d6 and
d
in ppm): 3.41 (CH2), 5.02 (CH), 5.20 (NH), 6.61 (Ph), 6.85 (Ph),
3.3.1. 1,4-Dihydro-2,6-dimethyl-4-phenyl-3,5-diethyl-ester-3,5-
7.07e8.01 (Ph). 13C NMR (75 MHz, DMSO-d6): 162.0, 160.1, 154.1,
149.2, 147.9, 143.9, 139.3, 136.7, 136.6, 136.4, 136.0, 131.3, 130.5,
130.2, 128.7, 128.6, 127.8, 126.6, 123.5, 122.4, 122.2, 122.1, 121.9,
114.2, and 30.6. This compound was very unstable.
pyridinedicarboxylic aciddDHP(a). 1H NMR (300 MHz DMSO-d6
and
d in ppm) 1.30 (6H, t, J 7.0 Hz, OCH2Me), 2.24 (6H, s, Me), 3.96
(2H, q, J 7.0 Hz, OCH2Me), 3.98 (2H, q, J 7.0 Hz, OCH2Me), 4.84 (1H, s,
CH), 7.20e7.06 (5H, m, Ph) and 8.79 (1H, s, NH). 13C NMR (75 MHz,
DMSO-d6) 167.4, 148.6, 147.8, 128.2, 127.8, 126.3, 102.3, 59.4, 18.7,
14.6, and 7.2.
3.3.10. 3-(1,3-Benzodioxol-5-yl)-3-[(4-nitrophenyl)amino]-1-
phenyl-1-propanonedBAK(e). 1H NMR (300 MHz DMSO-d6 and
d in
ppm): 3.76 (CH2), 5.17 (CH), 6.61 (Ph), 7.24 (Ph), 7.35 (Ph), 7.44e8.02
(Ph). 13C NMR (75 MHz, DMSO-d6): 196.5, 153.5, 142.5, 136.4, 135.8,
133.3, 128.6, 128.5, 128.0, 127.1, 126.5, 125.9, 52.2, 45.8, and 30.6.
This compound was very unstable.
3.3.2. 1,4-Dihydro-4-(3-hydroxyphenyl)-2,6-dimethyl-,3,5-diethyl
ester-3,5-pyridinedicarboxylic aciddDHP(b). 1H NMR (300 MHz
DMSO-d6 and
d in ppm) 2.23 (6H, t, J 7.0 Hz, OCH2Me), 2.50 (6H, s,
Me), 3.98 (4H, q, J 7 Hz, OCH2Me), 4.00 (4H, q, J 7 Hz, OCH2Me), 4.81
(1H, s, CH), 7.11e6.94 (5H, m, Ph), 8.77 (1H, s, OH) and 9.37 (1H, s,
NH). 13C NMR (75 MHz, DMSO-d6) 167.5, 157.4, 149.8, 145.6, 129.1,
129.0, 128.5, 108.3, 102.2, 59.4, 18.7, 14.6, and 7.2.
Acknowledgements
This work has been supported in part by CAPES, CNPq, FINEP-
MCT, FINATEC, FAPESP, FAPDF, DPP-UnB, INCT-Catalysis, INMETRO,
and ANP-PETROBRAS. DADN thanks Roberto F. de Souza for the
fruitful discussions regarding the IL effect.
3.3.3. 1,4-Dihydro-2,6-dimethyl-,3,5-diethyl ester,3,5-
pyridinedicarboxylic aciddDHP(c). 1H NMR (300 MHz DMSO-d6
and
d in ppm) 1.16 (6H, t, J 7.0 Hz, OCH2Me), 2.08 (6H, s, Me), 3.33
(1H, s, CHaHb), 3.05 (1H, s, CHaHb), 4.03 (4H, q, J 7.0 Hz, OCH2Me)
and 8.25 (1H, s, NH). 13C NMR (75 MHz, DMSO-d6) 167.5, 146.9, 97.4,
59.3, 18.4, 14.8, and 7.2.
Supplementary data
3.3.4. 9-(1,3-Benzodioxol-5-yl)-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-
acridinedionedDHP(d). 1H NMR (300 MHz CDCl3 and
2.00 (4H, m, CH2CH2CH2), 2.31 (4H, m, CH2CH2CH2), 2.60 (4H, m,
CH2CH2CH2), 4.72 (1H, s, CH), 5.8 (2H, s, OCH2O) and 6.66e6.78 (3H,
m, Ph), 7.26 (1H, s, NH). 13C NMR (75 MHz, CDCl3) 195.7, 166.9,
d
in ppm)
NMR spectra, Cartesian coordinates, energies and thermal cor-
rections for all of the calculated structures are available as Sup-
plementary data. Supplementary data related to this article can be
found at http://dx.doi.org/10.1016/j.tet.2013.10.033.

H.G.O. Alvim et al. / Tetrahedron 70 (2014) 3306e3313
3313
45. Cekavicus, B.; Vigante, B.; Rucins, M.; Birkmane, K.; Petrova, M.; Belyakov, S.; Zuka, L.;
Plotniece, A.; Pajuste, K.; Gosteva, M.; Sobolev, A. Tetrahedron 2013, 69, 5550e5557.
46. Shen, L.; Cao, S.; Wu, J. J.; Zhang, J.; Li, H.; Liu, N. J.; Qian, X. H. Green Chem.
2009, 11, 1414e1420.
References and notes
1. Brauch, S.; van Berkel, S. S.; Westermann, B. Chem. Soc. Rev. 2013, 42,
4948e4962.
47. Murthy, Y. L. N.; Rajack, A.; Ramji, M. T.; Babu, J. J.; Praveen, C.; Lakshmi, K. A.
2. Gupta, A. K.; Singh, N.; Singh, K. N. Curr. Org. Chem. 2013, 17, 474e490.
3. Ren, Y. M.; Cai, C.; Yang, R. C. RSC Adv. 2013, 3, 7182e7204.
4. Aleman, J.; Cabrera, S. Chem. Soc. Rev. 2013, 42, 774e793.
5. Domling, A.; Wang, W.; Wang, K. Chem. Rev. 2012, 112, 3083e3135.
6. Slobbe, P.; Ruijter, E.; Orru, R. V. A. Med. Chem. Commun. 2012, 3, 1189e1218.
7. Sheldon, R. A. Chem. Soc. Rev. 2012, 41, 1437e1451.
8. Singh, M. S.; Chowdhury, S. RSC Adv. 2012, 2, 4547e4592.
9. Syamala, M. Org. Prep. Proced. Int. 2009, 41, 1e68.
10. Gu, Y. L. Green Chem. 2012, 14, 2091e2128.
11. Climent, M. J.; Corma, A.; Iborra, S. RSC Adv. 2012, 2, 16e58.
12. Panda, S. S.; Khanna, P.; Khanna, L. Curr. Org. Chem. 2012, 16, 507e520.
13. de Graaff, C.; Ruijter, E.; Orru, R. V. A. Chem. Soc. Rev. 2012, 41, 3969e4009.
14. Toure, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439e4486.
15. Wegner, J.; Ceylan, S.; Kirschning, A. Adv. Synth. Catal. 2012, 354, 17e57.
16. Dupont, J.; Scholten, J. D. Chem. Soc. Rev. 2010, 39, 1780e1804.
17. Dupont, J. Acc. Chem. Res. 2011, 44, 1223e1231.
18. Scholten, J. D.; Leal, B. C.; Dupont, J. ACS Catal. 2012, 2, 184e200.
19. Chauvin, Y.; Mussmann, L.; Olivier, H. Angew. Chem., Int. Ed. 1996, 34,
2698e2700.
20. Carmichael, A. J.; Earle, M. J.; Holbrey, J. D.; McCormac, P. B.; Seddon, K. R. Org.
Lett. 1999, 1, 997e1000.
21. De Bellefon, C.; Pollet, E.; Grenouillet, P. J. Mol. Catal. A: Chem. 1999, 145,
121e126.
22. Hallett, J. P.; Welton, T. Chem. Rev. 2011, 111, 3508e3576.
23. Welton, T. Chem. Rev. 1999, 99, 2071e2083.
24. Welton, T. Coord. Chem. Rev. 2004, 248, 2459e2477.
25. Plechkova, N. V.; Seddon, K. R. Chem. Soc. Rev. 2008, 37, 123e150.
26. Petkovic, M.; Seddon, K. R.; Rebelo, L. P. N.; Pereira, C. S. Chem. Soc. Rev. 2011, 40,
1383e1403.
27. Isambert, N.; Duque, M. D. S.; Plaquevent, J. C.; Genisson, Y.; Rodriguez, J.;
Constantieux, T. Chem. Soc. Rev. 2011, 40, 1347e1357.
28. Shanab, K.; Neudorfer, C.; Schirmer, E.; Spreitzer, H. Curr. Org. Chem. 2013, 17,
1179e1187.
29. Sharma, N.; Kumar Sharma, U.; Kumar, R.; Richa; Kumar Sinha, A. RSC Adv.
2012, 2, 10648e10651.
30. Fang, D.; Zhang, D. Z.; Liu, Z. L. Monatsh. Chem. 2010, 141, 419e423.
31. Shaabani, A.; Rahmati, A.; Naderi, S. Bioorg. Med. Chem. Lett. 2005, 15,
5553e5557.
Bioorg. Med. Chem. Lett. 2012, 22, 6016e6023.
48. Montes-Avila, J.; Delgado-Vargas, F.; Diaz-Camacho, S. P.; Rivero, I. A. RSC Adv.
2012, 2, 1827e1834.
49. Kumar, R. S.; Idhayadhulla, A.; Nasser, A. J. A.; Selvin, J. Eur. J. Med. Chem. 2011,
46, 804e810.
50. Wynands, L.; Delacroix, S.; Nhien, A. N. V.; Soriano, E.; Marco-Contelles, J.;
Postel, D. Tetrahedron 2013, 69, 4899e4907.
51. Szatmari, I.; Fulop, F. Tetrahedron 2013, 69, 1255e1278.
52. Chen, F. L.; Lei, M.; Hu, L. H. Tetrahedron 2013, 69, 2954e2960.
53. Eftekhari-Sis, B.; Abdollahifar, A.; Hashemi, M. M.; Zirak, M. Eur. J. Org. Chem.
2006, 5152e5157.
54. Wang, R.; Li, B.-g.; Huang, T.-k.; Shi, L.; Lu, X.-x. Tetrahedron Lett. 2007, 48,
2071e2073.
55. Gong, K.; Fang, D.; Wang, H.-L.; Liu, Z.-L. Monatsh. Chem. 2007, 138, 1195e1198.
56. Arya, K.; Rajesh, U. C.; Rawat, D. S. Green Chem. 2012, 14, 3344e3351.
57. D’Oca, M. G. M.; Moraes, L. A. B.; Pilli, R. A.; Eberlin, M. N. J. Org. Chem. 2001, 66,
3854e3864.
58. Tomazela, D. M.; Moraes, L. A. B.; Pilli, R. A.; Eberlin, M. N.; D’Oca, M. G. M. J.
Org. Chem. 2002, 67, 4652e4658.
59. Pilli, R. A.; Russowsky, D. J. Org. Chem. 1996, 61, 3187e3190.
60. Russowsky, D.; Petersen, R. Z.; Godoi, M. N.; Pilli, R. A. Tetrahedron Lett. 2000, 41,
9939e9942.
61. Speckamp, W. N.; Moolenaar, M. J. Tetrahedron 2000, 56, 3817e3856.
62. Coelho, F.; Eberlin, M. N. Angew. Chem., Int. Ed. 2011, 50, 5261e5263.
63. Santos, L. S. J. Braz. Chem. Soc. 2011, 22, 1827e1840.
64. Orth, E. S.; Brandao, T. A. S.; Souza, B. S.; Pliego, J. R.; Vaz, B. G.; Eberlin, M. N.;
Kirby, A. J.; Nome, F. J. Am. Chem. Soc. 2010, 132, 8513e8523.
65. Amarante, G. W.; Benassi, M.; Pascoal, R. N.; Eberlin, M. N.; Coelho, F. Tetra-
hedron 2010, 66, 4370e4376.
66. Santos, L. S. Eur. J. Org. Chem. 2008, 235e253.
67. Corilo, Y. E.; Nachtigall, F. M.; Abdelnur, P. V.; Ebeling, G.; Dupont, J.; Eberlin, M.
N. RSC Adv. 2011, 1, 73e78.
68. Machado, A. H. L.; Milagre, H. M. S.; Eberlin, L. S.; Sabino, A. A.; Correia, C. R. D.;
Eberlin, M. N. Org. Biomol. Chem. 2013, 11, 3277e3281.
69. Gozzo, F. C.; Santos, L. S.; Augusti, R.; Consorti, C. S.; Dupont, J.; Eberlin, M. N.
Chem.dEur. J. 2004, 10, 6187e6193.
70. Chiappe, C.; Rajamani, S. Eur. J. Org. Chem. 2011, 5517e5539.
71. Johnson, K. E.; Pagni, R. M.; Bartmess, J. Monatsh. Chem. 2007, 138, 1077e1101.
72. Consorti, C. S.; Suarez, P. A. Z.; de Souza, R. F.; Burrow, R. A.; Farrar, D. H.; Lough,
A. J.; Loh, W.; da Silva, L. H. M.; Dupont, J. J. Phys. Chem. B 2005, 109, 4341e4349.
73. Dupont, J.; Eberlin, M. N. Curr. Org. Chem. 2013, 17, 257e272.
74. Lapis, A. A. M.; Neto, B. A. D.; Scholten, J. D.; Nachtigall, F. M.; Eberlin, M. N.;
Dupont, J. Tetrahedron Lett. 2006, 47, 6775e6779.
75. Kohn, W.; Sham, L. J. Phys. Rev. B 1965, 137, A1697eA1705.
76. Hohenberg, P.; Kohn, W. Phys. Rev. B 1964, 136, B864eB871.
77. Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215e241.
78. Boys, S. F.; Bernardi, F. Mol. Phys. 1970, 19, 553e566.
79. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J.
R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato,
M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.;
Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.;
Honda, Y.;Kitao, O.; Nakai, H.; Vreven, T.;Montgomery, J. A.; Peralta, J. E.; Ogliaro, F.;
Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.;
Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.;
Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V.
G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas;
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Wallingford C. T., 2009.
80. Kraus, G. A.; Guney, T. Green Chem. 2012, 14, 1593e1596.
32. Giernoth, R. Angew. Chem., Int. Ed. 2010, 49, 2834e2839.
33. Sebesta, R.; Kmentova, I.; Toma, S. Green Chem. 2008, 10, 484e496.
34. Lombardo, M.; Trombini, C. Chem. Cat Chem. 2010, 2, 135e145.
35. Lee, S. G. Chem. Commun. 2006, 1049e1063.
36. Ramos, L. M.; Tobio, A.; dos Santos, M. R.; de Oliveira, H. C. B.; Gomes, A. F.;
Gozzo, F. C.; de Oliveira, A. L.; Neto, B. A. D. J. Org. Chem. 2012, 77, 10184e10193.
37. Ramos, L. M.; Guido, B. C.; Nobrega, C. C.; Correa, J. R.; Silva, R. G.; de Oliveira, H.
C. B.; Gomes, A. F.; Gozzo, F. C.; Neto, B. A. D. Chem.dEur. J. 2013, 19, 4156e4168.
38. Alvim, H. G. O.; de Lima, T. B.; de Oliveira, H. C. B.; Gozzo, F. C.; de Macedo, J. L.;
Abdelnur, P. V.; Silva, W. A.; Neto, B. A. D. ACS Catal. 2013, 3, 1420e1430.
39. dos Santos, M. R.; Gomes, A. F.; Gozzo, F. C.; Suarez, P. A. Z.; Neto, B. A. D.
ChemSusChem 2012, 5, 2383e2389.
40. dos Santos, M. R.; Diniz, J. R.; Arouca, A. M.; Gomes, A. F.; Gozzo, F. C.; Tam-
borim, S. M.; Parize, A. L.; Suarez, P. A. Z.; Neto, B. A. D. ChemSusChem 2012, 5,
716e726.
^
41. Oliveira, F. F. D.; dos Santos, M. R.; Lalli, P. M.; Schmidt, E. M.; Bakuzis, P.; Lapis,
A. A. M.; Monteiro, A. L.; Eberlin, M. N.; Neto, B. A. D. J. Org. Chem. 2011, 76,
10140e10147.
42. Zhu, W. S.; Huang, W. L.; Li, H. M.; Zhang, M.; Jiang, W.; Chen, G. Y.; Han, C. R.
Fuel Process. Technol. 2011, 92, 1842e1848.
43. Shagun, V. A.; Medvedeva, A. S.; Mareev, A. V. Tetrahedron 2013, 69, 2357e2368.
44. Liu, Y. P.; Liu, J. M.; Wang, X.; Cheng, T. M.; Li, R. T. Tetrahedron 2013, 69,
5242e5247.