[Omim][Bf4] ionic liquid, a green and recyclable medium for one-pot aminomethylation of electron-rich aromatic compounds

Article abstract of DOI:10.3184/174751913X13635476751996

An efficient catalyst-free procedure has been developed for one-pot aminomethylation of some electron-rich aromatic compounds such as 1- and 2-naphthols, indole, N-methylindol and benzamide, in [omim][BF₄] ionic liquid at room temperature. The ionic liquid can be recovered and reused without any noticeable loss of performance.

Full text of DOI:10.3184/174751913X13635476751996

216 RESEARCH PAPER
APRIL, 216–218
JOURNAL OF CHEMICAL RESEARCH 2013
[Omim][BF4] ionic liquid, a green and recyclable medium for one-pot
aminomethylation of electron-rich aromatic compounds
Amene Yaghoubi Arzephonia, M. Reza Naimi-Jamala*, Ali Sharifib, M. Saeed Abaeeb and
Mojtaba Mirzaeib
aResearch Laboratory of Green Organic Synthesis and Polymers, Department of Chemistry, Iran University of Science andTechnology,
Tehran 16846-13114, Iran
bChemistry and Chemical Engineering Research Center of Iran, P.O.Box 14335-186, Tehran, Iran
An efficient catalyst-free procedure has been developed for one-pot aminomethylation of some electron-rich aro-
matic compounds such as 1- and 2-naphthols, indole, N-methylindol and benzamide, in [omim][BF4] ionic liquid at
room temperature. The ionic liquid can be recovered and reused without any noticeable loss of performance.
Keywords: aminomethylation, electron-rich aromatic compounds, one-pot reaction, green chemistry, [omim][BF4] ionic liquid,
Mannich reaction
The aminomethylation of electron-rich aromatic compounds
by the Mannich reaction is of value in the chemistry of drugs,
pesticides, pharmaceutical and natural products.1,2 In addition,
the reaction has found applications in plant protection and in
paint and polymer chemistry.3 The utilisation of Mannich bases
in cancer treatment is another interesting area of research.4 The
reaction also affords a facile access to many versatile synthetic
building blocks which can easily be converted into a range
of useful and valuable derivatives. Such derivatives consist
of Michael acceptors, 1,3-amino alcohols and functionalised
carbonyl compounds.5 Different substrates have been used as
the CH-acidic component in Mannich reaction, such as ketones,
β-ketoesters, malonates and nitro compounds.4
[Omim][BF4] ionic liquid at room temperature. The process
leads to an efficient synthesis of some Mannich bases under
mild conditions using no additive nor catalyst.
Results and discussion
Effect of different ionic liquids
Initially, the effect of different ionic liquids 1-ethyl-3-methyl-
imidazoliumtetrafluoroborate([emim][BF4]),1-butyl-3-methy-
limidazoliumtetrafluoroborate([bmim][BF4]),1-octyl-3-meth-
ylimidazolium tetrafluoroborate ([omim][BF4]), and 1-butyl-
2,3-dimethylimidazolium tetrafluoroborate ([bdmim][BF4])
With increasing concerns over pollution and serious envi-
ronmental mandates enforced on industry and academia, ionic
liquids have attracted extensive interest in recent years as
excellent alternatives to conventional organic solvents. Their
favourable properties and applications make them be both
catalysts and solvents in chemical research and industry.6,7
Ionic liquids have become very useful solvents for synthetic
organic transformations as a result of their simplicity of recov-
ery, very low vapour pressure, thermal stability, and their
ability to dissolve a broad range of organic compounds.8–11
The use of three component one-pot strategies is preferred
for the synthesis of a diverse array of Mannich bases. This
involves the in-situ formation of iminium intermediates from
paraformaldehyde and secondary amines which are readily
available with a wide range of structural variations. So far, a
few three-component related procedures involving electron-
rich aromatic compounds have been reported using different
media or catalysts such as acidic alumina (Al2O3),12–14 p-tolu-
ene sulfonic acid (p-TSA) under microwave irradiation,15,16 dry
benzene at reflux,17 conc. HCl or NaOH,18,19 and functionalised
ionic liquids.20–22 Some of these methods suffer from the use of
strong acidic or basic conditions, long reaction times, toxic
reagents, low yields, and cumbersome preparation of the
catalysts. Hence, there is an increasing interest in developing
environmentally benign and atom-economic catalytic
processes for the synthesis of Mannich bases.
Table 1 Mannich reaction of paraformaldehyde, pyrrolidine
and β-naphthol in the presence of different ionic liquidsa
Entry
1
Ionic liquid
Time/h
1.5
Yield/%
92
2
3
3
1
88
95
4
2.5
75
a The reaction was carried out at room temperature.
Table 2 Investigation of the amount of [omim][BF4]a
Entry
mmol of [omim]BF4
Time/h
Yield/%b
1
2
3
4
2.5
2.8
3.5
4.5
1
1
1
1
86
95
93
80
a The reaction conditions: paraformaldehyde (1.5 mmol),
pyrrolidine (1.5 mmol), β-naphthol (1.0 mmol).
b Isolated yield.
Here we report a three-component aminomethylation of
various electron-rich aromatic compounds in the presence of
Scheme 1
* Correspondent. E-mail: naimi@iust.ac.ir

JOURNAL OF CHEMICAL RESEARCH 2013 217
Table 3 Room-temperature, [omim][BF4] mediated Mannich reactions with CH2O, amines and electron-rich aromatic compounds
Entry
Amine (1)
Aromatic compound (2)
Product (3)
Time /h Yield/%
M.p./°C
1
1
2
93
70
87–88
[86–88]23
2a
1a
3a
2
3
4
2a
115–116
[114–116]15
1b
1c
3b
2a
2a
1.5
1.5
80
99
94.5–95
[94.5–95.5]24
3c
Oil12
1d
3d
5
6
7
NH(Bu)2 1e
2a
2a
1.5
6
70
75
60
Oil12
3e
117–118
[117–117.5]19
1f
3f
1a
1.5
Oil25
Oil17
2b
3g
8
9
1b
1c
2b
4
3
65
54
3h
3i
2b
135–136
[133.5–134.5]24
10
11
1b
1b
24
34
Oil5
2c
2d
3j
12
3
69
120–121
87a
[118–119]26
3k
12
13
1c
2d
12
72
161–162
[162–163]26
3l
1b
5.5
3
80
66–68
90a
[67–68]14
2e
3m
14
1c
2e
4
84
125–127
[128]14
3n
a The reaction was carried out at 80 °C.

218 JOURNAL OF CHEMICAL RESEARCH 2013
solutions with TMS as the internal standard. Infrared spectra were
recorded using KBr pellets on a FT-IR Shimadzu 8400S spectrometer.
Melting points were determined using an Electrothermal 9100 appara-
tus. All chemicals and reagents were purchased from Merck Company
and used without further purification except for benzaldehyde which
was distilled prior to being used. Analytical TLC was carried out using
Merck 0.2 mm silica gel 60 F-254 Al-plates. All yields refer to the
isolated products after purification. The ionic liquids [emim]BF4 and
[bmim]BF427, [omim]BF428, and [bdmim]BF429 were prepared using
available procedures,. All the products were known and were identi-
fied by comparison of their melting points and/or spectroscopic data
with those reported in the literature.
on the three-component Mannich reaction of paraformalde-
hyde, pyrrolidine and β-naphthol as the model reaction
(Scheme 1) was examined in order to find the ionic liquid with
the best catalytic effects. The results in Table 1 show that
among various ionic liquids used in the model reaction,
[omim][BF4] had the best performance in respect to the
reaction time and the yield of the product (Table 1, entry 3).
Effect of amounts of [omim][BF4]
In order to optimise the reaction condition, the use of different
amounts of [omim][BF4] was evaluated in the model reaction.
From the data presented in the Table 2, it is obvious that the
optimum result was obtained when the reaction was carried
out in 2.8 mmol of the ionic liquid (Table 2, entry 2).
The optimised conditions were then employed to evaluate
the generality of the procedure (Table 3). In the reactions of
2-naphthol with formaldehyde and cyclic or acyclic amines,
the Mannich bases were obtained in good to excellent yields
within short times (entries 1–6). 1-Naphthol (entries 7–9),
indole derivatives (entries 10–12), and benzamide (entries 13
and 14) also reacted well under the same conditions to give
their respective products, although lower yields were obtained
in some cases.
Typical procedure
A mixture of paraformaldehyde (1.5 mmol), a secondary amine
(1.5 mmol), and an aromatic compound (1.0 mmol) in [omim][BF4]
(2.8 mmol) was stirred at room temperature for the appropriate length
of time (Table 3). After completion of the reaction, based on TLC
monitoring, the reaction mixture was extracted with Et2O (3 × 10 mL).
The extract was washed with brine (20 mL), dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The crude product
was purified by column chromatography using silica gel and EtOAc/
hexane as the eluent (if necessary) or recrystallised from hexane and
ethanol. The products were dried under vacuum at 40° C.
We acknowledge partial financial support by the Research
Council of Iran University of Science and Technology (IUST).
Reusability and recovery
The reusability of the ionic liquid was investigated in consecu-
tive Mannich reactions of paraformaldehyde and pyrrolidine
with 2-naphthol. The reactions were carried out by following
the typical procedure. At the end of each reaction and after
extraction of the products, the ionic liquid was recovered by
removing the volatile solvent under reduced pressure using
a rotary evapourator. The results of the reuse of the ionic
liquid are summarised in the Fig. 1. As it is shown, the ionic
liquid can be used for at least four consecutive runs without
considerable loss of its catalytic activity.
Received 26 November 2012; accepted 11 February 2013
Paper 1201579 doi: 10.3184/174751913X13635476751996
Published online: 19 April 2013
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