Anion-Dependent Imidazolium-Based Catalysts for Allylation of Aniline with Tunable Regioselectivity

Article abstract of DOI:10.1002/adsc.202000102

Metal-free catalysts based on 1,3-bis(carboxymethyl)imidazolium halides mediate the reaction between allylic alcohols and anilines, providing the corresponding N-, 2- and 4-allylaniline isomers selectively. The imidazolium counterion plays a crucial role

Full text of DOI:10.1002/adsc.202000102

Title: Anion-dependent imidazolium-based catalysts for allylation of
aniline with tunable regioselectivity
Authors: María Albert-Soriano and Isidro Pastor
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000102
Link to VoR: http://dx.doi.org/10.1002/adsc.202000102

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Anion-Dependent Imidazolium-Based Catalysts for Allylation
of Aniline with Tunable Regioselectivity
María Albert-Sorianoa and Isidro M. Pastora*
a
Organic Chemistry Department and Instituto de Síntesis Orgánica (ISO), University of Alicante, Apdo. 99, 03080
Alicante, Spain
Fax: (+34)965903549; phone: (+34)965903728; e-mail: ipastor@ua.es
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract.
Metal-free
catalysts
based
on
1,3- A set of complementary catalysts, which are available by
bis(carboxymethyl)imidazolium halides mediate the reaction simple modulation, is here presented to conduct a highly
between allylic alcohols and anilines, providing the regioselective allylation reaction of anilines. Not only the
corresponding N-, 2- and 4-allylaniline isomers selectively. catalysts are synthesized in a straightforward and easily
The imidazolium counterion plays a crucial role in the scalable manner, but they can be recycled and used under
outcome of the reaction. Thus, while the imidazolium chloride solvent-free reaction condition, due to the favorable
selectively provides the N-substituted aniline, the bromide interactions with the reactants.
and iodide imidazolium salts produce the 2- and 4-allylaniline
isomers, respectively, with excellent selectivities.
Keywords: Allylic Substitution; Heterogeneous catalysis;
Imidazolium salt; Metal-free; Regioselectivity;
Sustainability
substituted anilines, which rules out the possibility of
the aniline acting as N-nucleophile.
Introduction
We have proved that the imidazolium salt 1,3-
bis(carboxymethyl)imidazolium chloride (bcmim-Cl),
can be used as simple, efficient, regioselective and
recyclable metal-free catalyst for the preparation of N-
allylanilines by allylic substitution of alcohols with
anilines.[13] Both the carboxyl and chloride moieties in
the bcmim-Cl are responsible of the favorable
interactions with the reactants and key in the effective
preparation of quinoline and acridine derivatives.[14]
We hypothesized that different counteranions in the
imidazolium salt could result in a modification in the
outcome of allylic substitution reaction of alcohols
with anilines. Interestingly, the replacement of the
anion for other halide (i.e. bromide and iodide)
allowed the selective formation of both 2- and 4-
allylanilines, respectively (Scheme 1). Herein, we
report our finding in the development of metal-free
catalytic systems for the regioselective allylic
substitution of alcohols with anilines. The catalytic
The direct allylic substitution reaction of alcohols is a
straightforward strategy to afford allylic derivatives
avoiding the use of coupling agents or the necessity of
derivatization (e.g. acetates, phosphates, carbonates,
halides),[1] constituting an environmentally friendly
alternative. When the nucleophile is an aniline
derivative, three regioisomers are expected: 2-
allylanilines, 4-allylanilines and N-allylanilines. Most
of the reported catalytic systems for the allylic
substitution of alcohols with anilines lead to the
predominant generation of N-allylanilines,[2] and
include metals such as palladium,[3] gold,[4]
platinum,[3a,5] iron,[6] molybdenum[7] and cobalt,[8]
amongst others. The formation of 2- and 4-
allylanilines has been less studied. To the best of our
knowledge, the formation of 2-allylanilines (via allylic
substitution of alcohols with anilines) has been
achieved
using
Cu(OTf)2,[9]
Re2O7,[10]
a
palladacycle[3d] and iron-based imidazolium salts
(IBLAILs),[6a] while the synthesis of 4-allylanilines
has only been reported using Cu(OTf)2.[9] A carboxylic
acid functionalized graphene oxide[11] and a cubane-
type sulfido cluster incorporating palladium and
molybdenum[12] have also been used for the synthesis
of 4-allylanilines, starting from N,N-dialkyl
systems
are
based
on
1,3-
bis(carboxymethyl)imidazolium halides (bcmim-X),
which are ionic organic solids (IOS). These organic
salts can be easily separated from the reaction mixture.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
compound 4aa (78% conversion, Table 1, entry 10)
when bcmim-Br was employed as catalyst. Under
these conditions, bcmim-I gave a mixture of isomers
4aa and 5aa with low selectivity (ratio 1:3, Table 1,
entries 13 and 14), being remarkable that isomer 3aa
was not observed with this catalyst under any reaction
conditions. Consequently, the modulation of the
counteranion of this simple type of catalysts allows the
selective preparation of N-allylaniline (using bcmim-
Cl),[13] 2-allylaniline (using bcmim-Br) or 4-
allylaniline derivatives (using bcmim-I).
Table 1. (E)-1,3-diphenylprop-2-en-1-ol (1a) and aniline
(2a): Effect of the catalyst
Scheme 1. Metal-free catalyzed substitution reaction of
allylic alcohols with anilines: selective formation of the
products by modulation of the catalytic system.
Results and Discussion
Entry IOS
Temp
(ºC)
Time
(h)
Conv. (%)a)
3aa/4aa/5aa
The different 1,3-bis(carboxymethyl)imidazolium
halide catalysts were prepared by a simple procedure,
starting from glyoxal, formaldehyde and glycine, and
introducing the anion in the last step by treatment with
the corresponding hydrogen halide.
1
2
3
4
5
6
7
8
80
80
80
100
100
80
80
80
100
100
80
80
100
100
1.5
6
24
1
24
1.5
6
24
1
24
6
24
1
82/3/4
bcmim-Cl
bcmim-Cl
bcmim-Cl
bcmim-Cl
bcmim-Cl
bcmim-Br
bcmim-Br
bcmim-Br
bcmim-Br
bcmim-Br
bcmim-I
60/14/14
48/18/14
80/9/6
1/69/15
60/0/0
66/12/11
48/28/13
62/13/14
0/78/16
0/1/77
The use of 1,3-bis(carboxymethyl)imidazolium
chloride (bcmim-Cl) as heterogeneous catalyst in the
reaction of trans-1,3-diphenylprop-2-en-1-ol (1a) and
aniline (2a) at 80 ºC provided, after 90 minutes, the
selective formation of product 3aa in 82% conversion
(Table 1, entry 1),[13] with less than 5% of each of the
other isomers being detected. Longer reaction times
resulted in the formation of larger amounts of isomers
4aa and 5aa (14-18% and 14% conversion,
respectively, after 6-24 h, Table 1, entries 2, 3). The
temperature has also an influence in the reaction
selectivity. In our previous work,[13] we proved that
both the ortho- and the para-allylanilines (i.e. 4aa and
5aa) can be formed, in low selectivity, from the N-allyl
substituted product 3aa by increasing the temperature
and the reaction time (Table 1, entries 4 and 5), using
bcmim-Cl as catalyst. Interestingly, the use of the
imidazolium iodide analogue as catalyst (10 mol%) in
our model reaction, resulted in a drastic change in the
selectivity and product 5aa was formed in 77%
conversion after 6 h (Table 1, entry 11). Next, we
9
10
11
12
13
14
0/2/78
0/23/67
0/21/66
bcmim-I
bcmim-I
bcmim-I
24
a) Conversion determined by GC analysis for the compounds
3aa, 4aa and 5aa.
Under the optimised reaction conditions  bcmim-
Br (10 mol%), 100 ºC, 24 h for the synthesis of 2-
allylanilines and bcmim-I (10 mol%), 80 ºC, 6 h for
the preparation of 4-allylanilines  the scope of the
reaction was explored.
The 2-allylation reaction of trans-1,3-diphenyl-2-
propen-1-ol, catalysed by bcmim-Br, was carried out
with different anilines (Scheme 2). Aniline, 4-
toluidine, 4-anisidine and 4-phenoxyaniline afforded
the corresponding compounds 4aa-4ad with
conversions between 60 and 93% (Scheme 2).
Halogen substituted anilines provided also the
expected 2-allylanilines in moderate conversions
(Scheme 2, compounds 4ae and 4af). Products 4 were
isolated with lower yields due to the purification
process (Scheme 2, isolated yields in brackets). 3,4-
Dimethoxyaniline gave the desired compound 4ag in
explored
the
reaction
using
1,3-
bis(carboxymethyl)imidazolium bromide (bcmim-
Br) as catalyst (Table 1, entries 6-10). Similar results
to bcmim-Cl were obtained at low temperature (80 ºC),
being the N-allylated aniline 3aa the major product of
the reaction (Table 1, compare entries 1-3 with entries
6-8). However, as also observed with catalysts
bcmim-Cl (Table 1, entry 5), increasing the
temperature to 100 ºC and extending the reaction time
to 24 h, resulted in the selective formation of
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
excellent conversion and good isolated yield (Scheme
2).
Scheme 2. Evaluation of anilines for the formation of 2-
allyl-anilines using bcmim-Br as catalyst. Reaction
conditions: 1 (0.5 mmol), 2 (0.5 mmol), bcmim-Br (10
1
mol%), 100 ºC, 24 h. Conversion determined by H-NMR
analysis (in brackets, isolated yield of pure product after
column chromatography).
Next, we studied the effect of substituents in
aromatic rings of the 1,3-diaryl-2-propen-1-ol. As
previously reported for N-allylanilines,[13] non-
symmetrically substituted alcohols led to the
formation of two 2-allylaniline regioisomers. The
regioisomers ratio was ca. 1:1 for different anilines
and alcohols, regardless of the electron properties of
the substituents. This agrees with the fact that 2-
allylanilines are formed from N-allylanilines, which
are formed via a carbocation intermediate. Thus,
alcohols and anilines bearing both electron-donating
and electron-withdrawing groups were evaluated in
the reaction leading to the formation of the
corresponding 2-allylanilines in moderate conversions
and yields (Scheme 3, compounds 4be, 4cd, 4cf and
their corresponding regioisomers). Using 3,4-
dimethoxyaniline in combination with trans-1-(4-
chlorophenyl)-3-phenyl-2-propen-1-ol produced the
expected compound 4bg in excellent conversion and
yield (Scheme 3, compound 4bg and regioisomer
4bg’).
Scheme 3. Evaluation of alcohols for the formation of 2-
allyl-anilines using bcmim-Br as catalyst. Reaction
conditions: 1 (0.5 mmol), 2 (0.5 mmol), bcmim-Br (10
1
mol%), 100 ºC, 24 h. Conversion determined by H-NMR
analysis (in brackets, isolated yield of pure product after
column chromatography), [in square brackets, ratio of the
regioisomers determined by 1H-NMR].
Next, we explored the reaction of trans-1,3-
diphenylprop-2-en-1-ol (1a) with bcmim-I in the
presence of different substituted anilines, under the
optimized reaction conditions, for the synthesis of the
corresponding 4-allylaniline adducts. Thus, anilines
with electron-withdrawing groups afforded the
corresponding 4-allylanilines in excellent conversions,
compounds 5ah, 5ai, 5aj, 5ak and 5al being isolated
with good yields (Scheme 4). Substituted anilines in
both ortho-positions, such as 2-chloro-6-methylaniline
and 2,6-diisopropylaniline, led to the quantitative
formation of the desired compounds 5am and 5an
respectively (Scheme 4) without any further
purification, apart from separation of the catalyst by
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
filtration. 2,5-Dimethylaniline afforded the desired
product 5ao in excellent conversion and yield (Scheme
4). Finally, 2-benzoylaniline gave rise to the formation
of the desired product 5ap in good conversion and
yield (Scheme 4).
Scheme 4. Evaluation of anilines for the formation of 4-
allylanilines using bcmim-I as catalyst. Reaction
conditions: 1 (0.5 mmol), 2 (0.5 mmol), bcmim-I (10
1
mol%), 80 ºC, 6 h. Conversion determined by H-NMR
analysis (in brackets, isolated yield of pure product after
column chromatography). aPure product isolated after
simple filtration.
Scheme 5. Evaluation of alcohols for the formation of 4-
allyl-anilines using bcmim-I as catalyst. Reaction
conditions: 1 (0.5 mmol), 2 (0.5 mmol), bcmim-I (10
1
mol%), 80 ºC, 6 h. Conversion determined by H-NMR
analysis (in brackets, isolated yield of pure product after
column chromatography), [in square brackets, ratio of the
regioisomers determined by 1H-NMR].
Other allylic alcohol derivatives were tested in the
reaction mediated by bcmim-I in combination with a
variety of anilines. Likewise, both regioisomers (in ca.
1:1 ratio) were obtained with non-symmetrically
substituted allylic alcohols. Alcohols bearing electron-
withdrawing and donating groups in the aromatic ring
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
were tested in combination with different anilines,
obtaining good to excellent conversions and yields in
Likewise, the amount of bromide in bcmim-Br was
reduced to less than 11%, compared with a fresh
all cases (Scheme 5, compounds 5bi, 5bo, 5cl and 5cm, sample, after the fifth cycle. For comparison, a
and their isomers). Moreover, compounds 5dj and 5dn
were isolated in 84% and 95% yield when trans-1,3-
di(4-chlorophenyl)-2-propen-1-ol was reacted with 2-
bromoaniline and 2,6-diisopropylaniline, respectively
(Scheme 5).
recycled sample of bcmim-Cl, which holds its activity
for 15 cycles, contains 16% of the initial amount of
chloride after fifteen cycles.[13] Although, the higher
robustness of the chloride salt is vindicated, it should
be noted that the reactivation of all three different
catalysts can be easily performed by treatment in the
corresponding acid medium.
Figure 1. Recycling of catalysts: (a) reaction of 1a and 2g
catalyzed by bcmim-Br; (b) reaction of 1a and 2m
catalyzed by bcmim-I.
The recyclability of both bcmim-Br and bcmim-I
catalysts was also studied. Due to their non-solubility
in organic solvents, such as ethyl acetate, the same
protocol employed for recycling bcmim-Cl[13] was
also applied here. The reaction mixture, after adding a
small portion of ethyl acetate, was centrifuged to
separate the catalyst; this protocol allowed the
complete recovery of the catalyst (no traces were
1
observed in the filtrate, H-NMR). The recovered
bcmim-Br catalyst could be recycled up to 3 times
without loss of activity in the synthesis of compound
4ag, observing a decrease in activity in the fourth cycle
(Figure 1a). Whereas, bcmim-I could be recycled up
to 5 times providing full conversion in the synthesis of
compound 5am, with a drastic reduction in the
conversion in the sixth cycle (Figure 1b). This
catalysts deactivation could be attributed to their
degradation. It has been proven that the effectiveness
of the catalyst depends, in part, on the halide, bearing
Scheme 6. Proposed mechanism for the formation of the
different regioisomers by allylic substitution of alcohols
with anilines.
Next, the synthetic utility of our methodology was
showcased by the ease of upscaling of the reaction,
allowing access to 1 g of 5am employing only 10
mol% of bcmim-I. Product 5am was isolated in
quantitative yield after filtration, using ethyl acetate (4
mL) to wash the catalyst. Interestingly, this reaction
presented an E-factor of 3.4, verifying the
sustainability of the protocol.[15]
Considering that the reactions are performed in the
absence of any solvent, it is postulated that the
catalysts facilitate the interactions between the
reactants. The presence of the carboxy groups in the
imidazolium catalyst, that enables the formation of
in
mind
that
the
zwitterion
[1,3-
bis(carboxymethyl)imidazole, bcmim] is inactive for
this type of transformation.[13] We pondered the
premise that the amount of halide could decrease
during the reaction and/or the work-up, the less bound
the halide is to the cation, the easier the dissociation.
Based on that idea, recycled bcmim-I (after the sixth
cycle) was analyzed by ionic chromatography
observing that the amount of iodide had been reduced
to less than 0.1% compared with a fresh sample.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
hydrogen bonds with the reagents, is key to the
catalytic process, although the interaction of the halide
with the reagents appears to be also crucial.[13-14] Thus,
it can be proposed that these bcmim-X salts, which are
ionic organic solids (IOS), establish favorable
interactions by acting both as hydrogen donors and
hydrogen acceptors. These interactions would favor
the formation of the allylic carbocation, which is
involved in the reaction mechanism, bringing the
amine closer to facilitate the nucleophilic attack
(Scheme 6). The measurement of the heat flow by
Differential Scanning Calorimetry (DSC) of mixtures
of the alcohol 1a and the different catalysts bcmim-X
(X = Cl, Br, I) showed differences compared with a
sample of pure alcohol 1a (Figure 2). The alcohol 1a
melting thermal event is modified by the presence of
the ionic organic salts (IOS), due to the favorable
interactions between the components in a similar way
as occurs between the components of a low transition
temperature mixtures (LTTM) or deep eutectic
solvents (DES).[16] Interestingly, in the presence of
both chloride and bromide salt, a similar decrease in
melting temperature is observed (Figure 2b and 2c),
but in the case of the iodide salt, the mixture shows a
greater variation (Figure 2d). Iodide has larger ionic
radius and higher polarizability than the other halides,
which may facilitate interactions with alcohol 1a. In
addition, the presence of an iodide would stabilize the
allyl carbocation generated during the reaction,
making the nucleophilic attack selective towards the
para position of the aromatic ring (Scheme 6). In the
cases of chloride and bromide the reaction occurs,
preferably, with the nitrogen acting as nucleophile,
forming the N-allyl product, which can equilibrate to
the more stable 2-allyl derivative (Scheme 6).
Moreover, the bcmim-I catalyst, apart from being
selective towards the 4-allyl product, is more effective
than the chloro and bromo imidazolium salts. It was
observed that the heat release in the reaction of alcohol
1a and aniline 2a in the presence of bcmim-I occurs at
lower temperature compared to the reactions catalyzed
by bcmim-Cl or bcmim-Br (Figure 3). Furthermore,
reactions catalyzed by bcmim-Cl and bcmim-Br
present similar DSC spectra, which agrees with the
observed experimental results. At this point, it is worth
mentioning that the selectivity in phenol tert-
butylation has been reported based on the acidic sites
of different catalysts,[17] so we cannot rule out certain
likeness with our case.
0
Heat Flow
(W/g)
(a)
-1
-2
-3
ROH
T = 58.6 ºC
T = 45.3 ºC
-4
0
Heat Flow
(W/g)
(b)
-0.5
-1
ROH + bcmim-Cl
-1.5
-2
0
Heat Flow
(W/g)
(c)
-1
-2
-3
ROH + bcmim-Br
T = 48.9 ºC
-4
0
Heat Flow
(W/g)
(d)
-0.5
-1
T = -3.0 ºC
ROH + bcmim-I
-1.5
-2
T (ºC)
-40 -20
0
20 40 60 80
Figure 2. Differential Scanning Calorimetry (DSC) spectra:
(a) alcohol 1a, (b) mixture of alcohol 1a and bcmim-Cl, (c)
mixture of alcohol 1a and bcmim-Br and (d) mixture of
alcohol 1a and bcmim-I.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
Table 2. (E)-1,3-diphenylprop-2-en-1-ol (1a) and aniline
(2a) catalyzed by hydrogen halides
0
Heat Flow
(W/g)
(a)
-0.05
-0.1
-0.15
-0.2
-0.25
0
40 50 60 70 80 90 100 110
Heat Flow
(W/g)
(b)
-0.05
-0.1
Entry
HX
Temp
(ºC)
Time (h) Conv. (%)a)
3aa/4aa/5aa
-0.15
-0.2
1
2
3
4
5
HCl
HBr
HBr
HI
80
6
1
24
1
6
51/4/0
100
100
80
58/24/16
0/59/40
38/22/34
0/42/58
-0.25
0.15
40 50 60 70 80 90 100 110
(c)
Heat Flow
(W/g)
HI
80
a) Conversion determined by GC analysis for the compounds
0.05
3aa, 4aa and 5aa.
-0.05
-0.15
-0.25
Conclusion
To conclude, we have described three simple, effective
and robust metal-free catalysts based on solid
imidazolium halides, which are complementary in
terms of regioselectivity for the allylic substitution of
alcohols with anilines. The counterion in the 1,3-
bis(carboxymethyl)imidazolium salt catalysts plays a
crucial role and determines the regioselectivity of the
process. Thus, the chloride catalyst selectively
produces N-allylanilines, the imidazolium bromide
generates 2-allylaniline isomers and the corresponding
iodide catalyst mediates the selective formation of 4-
allylanilines. Although bcmim-Cl catalyst proved to
be more robust than the others, with less degradation
during the successive cycles, bcmim-I catalyst
resulted more effective, allowing lower reaction
T (ºC)
40 50 60 70 80 90 100 110
Figure 3. Differential Scanning Calorimetry (DSC) spectra
of the reaction mixture: alcohol 1a, aniline (2a) and (a)
bcmim-Cl (10 mol%), (b) bcmim-Br (10 mol%) and (c)
bcmim-I (10 mo%).
Finally, different experiments were conducted in the
presence of HCl, HBr and HI, instead of the
imidazolium halides. The reactions were performed
under the optimized reaction conditions for each halide.
Thus, the reaction between alcohol 1a and aniline 2a,
using HCl (10 mol%) at 80 ºC, provided compounds
3aa and 4aa in 51% and 4% conversion, respectively,
after 6 h (Table 2, entry 1). The reaction of 1a and 2a,
employing HBr (10 mol%) as catalyst, afforded, after
1 h, products 3aa, 4aa and 5aa in 58%, 24% and 16%
conversion, respectively (Table 2, entry 2), although
after 24 h, only products 4aa and 5aa were observed
in 3:2 ratio (Table 2, entry 3). Similarly, the reaction
catalyzed by HI (10 mol%) gave, initially, all three
isomers 3aa, 4aa and 5aa (Table 2, entry 4), but
provided, after 6 h, the products 4aa and 5aa in 2:3
ratio (Table 2, entry 5). The results obtained with
hydrogen halides are in clear contrast with the ones
obtained employing bcmim-X catalysts (Table 1).
Indeed, the bcmim-X catalyzed reactions provide
higher regioselectivities than the corresponding
hydrogen halides; especially in the synthesis of the 4-
allylaniline isomers.
temperatures
and
providing
unprecedented
selectivities for the synthesis of 4-allylanilines. The
synthesis of all three catalysts is straightforward and
easily scalable. The catalytic allylation reaction is
carried out under solvent-free conditions, being the
catalysts responsible for the favorable interactions in
the absence of any solvent. Moreover, the catalysts are
easily separated from the reaction mixture and
recycled, which makes this methodology a sustainable
process. These protocols represent a significant
improvement compare with the previously reported
ones (most of them based on metals), particularly for
the 4-allylaniline isomers.
Experimental Section
Reagents and instruments. All commercially available
reagents and solvents were purchased (Acros, Aldrich,
Fluka) and used without further purification. Melting points
were determined using a Gallenkamp capillary melting
point apparatus (model MPD 350 BM 2.5) and are
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
uncorrected. 1H NMR and 13C NMR spectra were recorded
at the research technical service of the University of
Alicante (SSTTI–UA), employing a Bruker AC-300 or a
Bruker Advance-400.§ Chemical shifts (δ) are given in ppm
and the coupling constants (J) in Hz. The conversion of the
reactions and purity of the products were determined by GC
analysis using an Agilent 7820A apparatus, equipped with a
flame ionization detector and a Phenomenex ZB-5MS
column (5% PH-ME siloxane): 30 m (length), 0.25 mm
(inner diameter) and 0.25 μm (film). Low-resolution mass
spectra (EI) were obtained at 70 eV with an Agilent 5973
Network spectrometer, with fragment ions m/z reported with
relative intensities (%) in parentheses. Low-resolution
HPLC with electrospray ionization (HPLC-ESI) mass
spectra were recorded at the research technical service of the
University of Alicante (SSTTI–UA), employing an Agilent
1100 series apparatus with the possibility of MS/MS.§ High
resolution mass spectra (IE) were recorded at the research
technical service of the University of Alicante (SSTTI–UA)
with an Agilent 7200 Network spectrometer (Q-TOF).§ Ion
chromatography (IC) anions were measured at the research
technical service of the University of Alicante (SSTTI–UA)
with an Ion Chromatograph, with chemical suppression,
conductometric, amp and Spectrophotometric UV-VIS,
Metrohm, 850 detection ProfIC Acuma - MCS, with
derivatization post-column reactor.§ Differential Scanning
Calorimetry (DSC) spectra were recorded at the research
technical service of the University of Alicante (SSTTI–UA)
with a Heat Flow Q100 TA Instruments DSC equipped with
the catalyst. After evaporating the solvent under vacuum,
the corresponding crude was purified by column
chromatography using mixtures of hexane/ethyl acetate. In
the recycling experiments, the catalyst was separated by
centrifugation and washed with ethyl acetate (2×3 mL) and
with diethyl ether (1×3 mL).
Acknowledgements
This work was financially supported by the University of Alicante
(VIGROB-173, VIGROB-285 and VIGROB-316FI), the Spanish
Ministerio de Economía y Competitividad (CTQ2015-66624-P,
CTQ2017-88171-P), the Spanish Ministerio de Ciencia,
Innovación y Universidades (PGC2018-096616-B-I00) and the
Generalitat Valenciana (AICO/2017/007). M.A.-S. thanks the
Spanish Ministerio de Educación, Cultura y Deporte for a
predoctoral fellowship (FPU15/06040). We thank Dr. Beatriz
Macia-Ruiz (MMU) for valued suggestions.
References
[1] M. Johannsen, K. A. Jorgensen, Chem. Rev. 1998, 98,
1689-1708.
§
[2] K. Motokura, N. Nakagiri, T. Mizugaki, K. Ebitani, K.
temperature modulation. Infrared spectra were recorded
with an FT-IR 4100 LE (JASCO, Pike Miracle ATR)
spectrometer. Spectra were recorded from neat samples and
results are given in cm-1. Analytical TLC was performed on
Merck aluminum sheets with silica gel 60 F254, 0.2 mm
thick. Silica gel 60 (0.04-0.06 mm) was employed for
column chromatography. P/UV254 silica gel with CaSO4
supported on glass plates was employed for preparative
TLC. Centrifugation was carried out with a Nahita Model
2610 apparatus (4000 rpm).
Kaneda, J. Org. Chem. 2007, 72, 6006-6015.
[3] a) F. Ozawa, H. Okamoto, S. Kawagishi, S. Yamamoto,
T. Minami, M. Yoshifuji, J. Am. Chem. Soc. 2002, 124,
10968-10969; b) S.-C. Yang, Y.-C. Hsu, K.-H. Gan,
Tetrahedron 2006, 62, 3949-3958; c) Y. Wang, M. J. P.
Vaismaa, A. M. Haemaelaeinen, J. E. Tois, R. Franzen,
Tetrahedron: Asymmetry 2011, 22, 524-529; d) K. Chen,
Y. Li, S. A. Pullarkat, P.-H. Leung, Adv. Synth. Catal.
2012, 354, 83-87; e) D. Banerjee, K. Junge, M. Beller,
Angew. Chem. Int. Ed. 2014, 53, 13049-13053; f) Y.
Kwon, J. Jung, J. H. Kim, W.-J. Kim, S. Kim, Asian J.
Org. Chem. 2017, 6, 520-526.
Synthesis
of
1,3-bis(carboxymethyl)imidazole
(bcmim).[18] A mixture of glycine (100 mmol, 7.5 g),
glyoxal (40% in water, 50 mmol, 5.7 mL) and formaldehyde
(36% in water, 100 mmol, 3.9 mL) was stirred at 95 °C for
2 h. The mixture was cooled down to room temperature and
the resulting brown solid was filtered, washed with cold
water and dried at room temperature to afford the
corresponding product as a white solid in 89% yield.
[4] a) S. Guo, F. Song, Y. Liu, Synlett 2007, 964-968; b) Y.
Lu, X. Fu, H. Chen, X. Du, X. Jia, Y. Liu, Adv. Synth.
Catal. 2009, 351, 129-134; c) X. Giner, P. Trillo, C.
Najera, J. Organomet. Chem. 2010, 696, 357-361; d) T.
Ohshima, Y. Nakahara, J. Ipposhi, Y. Miyamoto, K.
Mashima, Chem. Commun. 2011, 47, 8322-8324; e) K.
Huang, H. Wang, L. Liu, W. Chang, J. Li, Chem. Eur. J.
2016, 22, 6458-6465; f) H. Gu, X. Sun, Y. Wang, H. Wu,
P. Wu, RSC Adv. 2018, 8, 1737-1743.
Synthesis of 1,3-bis(carboxymethyl)imidazolium halide
(bcmim-X).[18a,19] A mixture of bcmim (920 mg, 5 mmol)
and concentrated HCl (37% in water, 0.9 mL, 11.0 mmol),
HBr (48% in water, 0.9 mL, 16.5 mmol) or HI (57% in water,
1.2 mL, 16.5 mmol) was stirred and refluxed for 30 minutes.
Then, the corresponding hydrogen halide was removed
under reduced pressure and the resultant solid was filtered
and washed with acetone and diethyl ether to afford bcmim-
Cl and bcmim-Br as white solids in 93% and 91% yield
respectively, and bcmim-I as a reddish solid in 83% yield.
[5] T. Ohshima, Y. Miyamoto, J. Ipposhi, Y. Nakahara, M.
Utsunomiya, K. Mashima, J. Am. Chem. Soc. 2009, 131,
14317-14328.
General procedure for the synthesis of 2-allylanilines (4).
The corresponding allylic alcohol (1, 0.5 mmol), the
corresponding aniline (2, 0.5 mmol) and bcmim-Br (10
mol%, 13.3 mg) were placed in a tube provided with a
stirring bar. The mixture was stirred at 100 °C for 24 h. Then,
ethyl acetate (3 mL) was added, and the mixture was filtered
to separate the catalyst. After evaporating the solvent under
vacuum, the corresponding crude was purified by column
chromatography using mixtures of hexane/ethyl acetate. In
the recycling experiments, the catalyst was separated by
centrifugation and washed with ethyl acetate (2×3 mL) and
with diethyl ether (1×3 mL).
[6] a) P. Trillo, I. M. Pastor, Adv. Synth. Catal. 2016, 358,
2929-2939; b) P. Trillo, A. Baeza, C. Najera,
ChemCatChem 2013, 5, 1538-1542; c) P. Trillo, A.
Baeza, C. Najera, Eur. J. Org. Chem. 2012, 2929-2934;
d) Y. Zhao, S. W. Foo, S. Saito, Angew. Chem. Int. Ed.
2011, 50, 3006-3009.
[7] H. Yang, L. Fang, M. Zhang, C. Zhu, Eur. J. Org. Chem.
2009, 666-672.
General procedure for the synthesis of 4-allylanilines (5).
The corresponding allylic alcohol (1, 0.5 mmol), the
corresponding aniline (2, 0.5 mmol) and bcmim-I (10 mol%,
15.6 mg) were placed in a tube provided with a stirring bar.
The mixture was stirred at 80 °C for 6 h. Then, ethyl acetate
(3 mL) was added, and the mixture was filtered to separate
[8] H. Hikawa, Y. Ijichi, S. Kikkawa, I. Azumaya, Eur. J.
Org. Chem. 2017, 465-468.
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
[9] K. Chen, H. J. Chen, J. Wong, J. Yang, S. A. Pullarkat,
K. S. Ryder, Chem. Rev. 2014, 114, 11060-11082; e) I.
Hawkins, S. T. Handy, Tetrahedron 2013, 69, 9200-
9204; f) M. Francisco, A. van den Bruinhorts, M. C.
Kroon, Angew. Chem. Int. Ed. 2013, 52; g) C. Rus, B.
König, Green Chem. 2012, 14, 2969-2982.
ChemCatChem 2013, 5, 3882-3888.
[10] R. Nallagonda, M. Rehan, P. Ghorai, J. Org. Chem.
2014, 79, 2934-2943.
[11] M. Gómez-Martínez, A. Baeza, D. A. Alonso,
[17] a) A. B. Shinde, N. B. Shrigadi, S. D. Samant, Appl.
Catal. A Gen. 2004, 276, 5-8; b) X. Nie, X. Liu, C. Song,
X. Guo, J. Mol. Catal. A: Chem. 2010, 332, 145-151; c)
K. S. Kanakikodi, S. R. Churipard, A. B. Halgeri, S. P.
Maradur, Microporous Mesoporous Mater. 2019, 286,
133-140.
ChemCatChem 2017, 9, 1032-1039.
[12] Y. Tao, B. Wang, J. Zhao, Y. Song, L. Qu, J. Qu, J.
Org. Chem. 2012, 77, 2942-2946.
[13] M. Albert-Soriano, L. Hernández-Martínez, I. M.
Pastor, ACS Sustainable Chem. Eng. 2018, 6, 14063-
14070.
[18] a) M. Albert-Soriano, P. Trillo, T. Soler, I. M. Pastor,
Eur. J. Org. Chem. 2017, 6375-6381; b) O. Kühl, G.
Palm, Tetrahedron: Asymmetry 2010, 21, 393-397.
[14] P. Gisbert, M. Albert-Soriano, I. M. Pastor, Eur. J. Org.
Chem. 2019, 4928-4940.
[19] Z. Fei, T. J. Geldbach, R. Scopelliti, P. J. Dyson,
[15] R. A. Sheldon, Chem. Soc. Rev. 2012, 41, 1437-1451.
Inorganic Chemistry 2006, 45, 6331-6337.
[16] a) D. J. Ramón, G. Guillena, Deep Eutectic Solvents,
Wiley-VCH, Weinheim, 2020; b) E. Massolo, S.
Palmieri, M. Benaglia, V. Capriati, F. M. Perna, Green
Chem. 2016, 18, 792-797; c) M. Capua, S. Perrone, F.
M. Perna, P. Vitale, L. Troisi, A. Salomone, V. Capriati,
Molecules 2016, 21, 924; d) E. L. Smith, A. P. Abbott,
§ For further information of the scientific equipment, see:
Research Technical Services - University of Alicante,
http://sstti.ua.es/en.
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000102
Advanced Synthesis & Catalysis
FULL PAPER
N
Anion-dependent imidazolium-based catalysts for
allylation of aniline with tunable regioselectivity
X¯
Cl¯
Br¯
I¯
Adv. Synth. Catal. Year, Volume, Page – Page
Complementary catalysts


No derivatisation
Use of catalyst
80 ºC, 2 h
100 ºC, 24 h
80 ºC, 6 h
11 products
16 products
Up to 99% yield
Up to 5 runs
Up to 1 g
21 products

Recoverable
Reusable
María Albert-Soriano, Isidro M. Pastor*
Up to 91% yield
Up to 4 runs
Up to 99% yield
Up to 15 runs



No solvent nor additives
Atom economy
Up to 3.3
g
10
This article is protected by copyright. All rights reserved.