S. Sardar, E. Jabeen, C.D. Wilfred et al.
Journal of Molecular Liquids 320 (2020) 114370
R1
Brönsted acidity, low vapor pressure, wide range of viscosities, high ther-
mal, oxidative and chemical stabilities [19–22]. The usage of Brönsted-
acidic ILs is in increased demand due to their high efficiency, recycling per-
formance and easy separation on reaction completion. The mechanistic
studies emphasizing the role of catalyst have also been performed for dif-
ferent catalysts including proline, Lewis and Brönsted acids and a wide va-
riety of organocatalysts for synthesis of β-amino carbonyl compounds
[23–25]. Among the reported multicomponent reactions (MCRs), the
mechanism proposed for Mannich reaction is least controversial and reac-
tion route is almost largely acceptable [26]. However, most of these sug-
gested mechanisms focus on formation of C\\C bond step, while
formation of iminium ion is not much highlighted. Insight grip on mecha-
nistic pathway is very significant to develop novel catalysts, upgrade
greener reaction conditions, for synthetic estimates, innovative appliances
and rational designs.
In this study, role of synthesized IL bearing camphorsulfonate moi-
ety as anion with imidazolium-based cations as catalytic entities has
been inspected deeply to develop a probable mechanism that is sup-
ported by both experimental and theoretical studies. The reaction pro-
ceeds via hydrogen bond-assisted mechanism and formation of
iminium ion with release of water molecule has been found as rate de-
termining step of the overall reaction. To extent of our knowledge, the
current study is first detailed investigation on influence of
camphorsulfonate-based IL on Mannich-type reactions and for iminium
ion formation as a critical intermediate for the entire mechanism.
O
O
R2
N
H
CHO
NH2
R2
R1
Ionic Liquid
r.t
or
or
O
+
R1
+
O
R2
N
H
Scheme 2. Mannich reaction catalysed by imidazolium based ILs.
liquid reaction mixture turned to viscous material and further to white
solid. The synthesized zwitterion was washed several times with
diethylether, dichloromethane and ethyl acetate (10 mL each). After dry-
ing, zwitterion was further taken in equimolar concentration with differ-
ent protic acids (hydrochloric acid, trifluoroacetic acid, sulfuric acid,
phosphoric acid, methane sulphonic acid, trifluoromethane sulphonic
acid, p-toluenesulphonic acid and camphor-10-sulphonic acid) at
85–90 °C for 4–6 h (Scheme 1). The corresponding ILs were formed quan-
titatively with high purity as assessed by NMR.
2.3. Mannich reaction: a typical procedure
In a classic tryout, aniline (0.9 mL, 10 mmol, 1 equiv.), benzaldehyde
(1 mL, 10 mmol, 1 equiv.), cyclohexanone/acetophenone (10 mmol, 1
equiv.) and stoichiometric amount of catalyst were placed in a round
bottom flask with a magnetic stirrer at a constant temperature water
bath at 25 °C (Scheme 2) [30,31]. The reaction mixture turned turbid
within minutes and progress of reaction was continuously monitored
by TLC. After completion of reaction, as indicated by TLC, the IL was sep-
arated from the product by adding 3–5 mL of water. The solid product
was filtered, dried and then recrystallized using acetonitrile and further
dried in vacuo until constant weight was obtained. Finally the water
layer containing IL was concentrated using rotary evaporator. After
washing with diethylether and ethyl acetate, IL was then vacuum
dried at 70 °C for 12 h and was reused for next cycle.
2. Experimental
2.1. Chemicals and instrumentation
The starting materials used for synthesis of protic ionic liquids (PILs),
including 1,3-propane sultone 99%, 1,4-butane sultone 99%, 1-H-
imidazole 98%, 1-methylimidazole 99%, 2-methylimidazole 99%, 1-
ethylimidazole 99%, 2-ethylimidazole 98%, 1-butylimidazole 98%, 2-
phenylimidazole 98%, benzimidazole 98%, hydrochloric acid 35–37%,
trifluoroacetic acid 99%, sulfuric acid 99%, trifluoromethanesulfonic
acid 99%, p-methylbenzenesulfonic acid 98%, phosphoric acid 85 wt%
in H2O, methanesulfonic acid 99.5% and (+)-10-camphorsulfonic acid
98% were purchased from Sigma Aldrich, Malaysia. NMR spectra were
recorded on a 400 MHz NMR Joel spectrometer using D2O or CDCl3 as
solvents. Chemical shifts were mentioned in ppm. IR spectra were re-
corded on a Nicolet FTIR spectrometer (400–4000 cm−1).
2.4. UV–Vis acidity evaluation of PILs by Hammett equation
The camphorsulfonate-based ILs were dissolved in dried methanol
and 4-nitroaniline was added as an indicator. The ILs and indicator
were taken at concentration of 3 × 10−2 mol/L and 7.5 × 10−5 mol/L, re-
spectively. The resulting solutions were shaken vigorously and then left
to stand for overnight. Then UV–visible absorption study was carried
out for the determination of Hammett acidity function in the range of
300–800 nm using Cary Series spectrophotometer of Agilent
Technologies.
2.2. Synthesis of ionic liquids
The synthesis of PILs has been carried out by using a similar method as
reported in literature with some modifications [27–29]. The method in-
volved the solvent-less reaction of 1,3-propane sultone or 1,4-butane
sultone with N-methylimidazole in equimolar ratio affording respective
zwitterions that were further converted to PILs by acidification with differ-
ent protic acids (Scheme 1). In a typical experiment, 1,3-propane sultone
(12.2 g, 0.1 mol, 1 equiv.) was drawn into two-necked round bottom
flask equipped with drying tube and 1-methylimidazole (8.21 g, 0.1 mol,
1 equiv.) was added drop wise at room temperature. Within 10 min, the
2.5. Viscosity measurement for camphorsulfonate-based PILs
Viscosity measurements were taken at ambient temperature using
an Anton Paar viscometer (SVM 3000). The instrument was initially
A
85-90 oC
HA
r.t.
-
N
N
O
O
N
N
N
N
SO3
SO3H
n
n
S
O
-
-
-
-
-
-
-
-
-
Where A = Cl , CF3COO , HSO4 , H2PO4 , CH3SO3 , CF3SO3 , p-TS , CS
n= 1 and/or 2
Scheme 1. Schematic diagram of ionic liquid syntheses.
2