Ionic liquid-immobilized proline(s) organocatalyst-catalyzed one-pot multi-component Mannich reaction under solvent-free condition

Article abstract of DOI:10.1007/s11164-020-04096-w

A highly efficient clean and simple methodology has been established for the one-pot Mannich reaction using ionic liquid-immobilized proline(s) organocatalyst under solvent-free conditions. The three components comprising substituted acetophenones, substituted aromatic aldehydes and substituted aromatic amines underwent Mannich reactions in the presence of 7?mol% of ionic liquid-immobilized proline(s) organocatalyst to provide β-amino carbonyl compounds in 2–3?h at room temperature with excellent yields. This methodology provides several advantages such as mild reaction conditions, short reaction time, low catalyst loading percentage, multi-component approach, transition metal-free and solvent-free synthesis. The ionic liquid-immobilized proline(s) organocatalyst was recycled and reused five times without a significant loss of its catalytic activity.

Full text of DOI:10.1007/s11164-020-04096-w

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04096-w
Ionic liquid‑immobilized proline(s)
organocatalyst‑catalyzed one‑pot multi‑component
Mannich reaction under solvent‑free condition
M. D. Prabhakara1 · Barnali Maiti1
Received: 1 November 2019 / Accepted: 21 January 2020
© Springer Nature B.V. 2020
Abstract
A highly efcient clean and simple methodology has been established for the one-
pot Mannich reaction using ionic liquid-immobilized proline(s) organocatalyst under
solvent-free conditions. The three components comprising substituted acetophe-
nones, substituted aromatic aldehydes and substituted aromatic amines underwent
Mannich reactions in the presence of 7 mol% of ionic liquid-immobilized proline(s)
organocatalyst to provide β-amino carbonyl compounds in 2–3 h at room tempera-
ture with excellent yields. This methodology provides several advantages such as
mild reaction conditions, short reaction time, low catalyst loading percentage, multi-
component approach, transition metal-free and solvent-free synthesis. The ionic liq-
uid-immobilized proline(s) organocatalyst was recycled and reused fve times with-
out a signifcant loss of its catalytic activity.
Graphic Abstract
R3
Reaction
Multicomponent
CHO
R2
HN
O
NH2
R3
Solvent-free
Synthesis
R1
Short Reaction Times
Excellent Yield
to
O
R2
22
examples
98%
Up
R1
N +
N
CF3CO2
O
Satisfactory Recyclability
No
-
N
H
O
Chromatography
IL-P
Organocatalyst
2-3 h
Neat,
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04096-w) contains supplementary material, which is available to authorized users.
Extended author information available on the last page of the article
Vol.:(0123456789)
1 3

M. Prabhakara, B. Maiti
Fig. 1 Representative β-amino carbonyl derivatives as marketed drugs
Keywords Solvent-free synthesis · Multi-component reaction · Ionic liquid-
immobilized proline(s) organocatalyst
Introduction
Multi-component Mannich reactions have acquired a growing consideration
because they address both the diversity and convolution in organic synthe-
sis. Thus, in principle, various sets of moderately complex arrangements can
be produced from simple starting constituents in a solitary reaction step [1–3].
Multi-component Mannich reactions are convergent chemical processes com-
prising the well-defned condensation of three reactants to form a product that
contains signifcant portions of all reactants, ideally all atoms. In this way, very
high levels of atom efciency can be extended while evading time-consuming
separation and purifcation of synthetic intermediates. Multi-component Man-
nich reaction is one of the most signifcant carbon–carbon bond formation reac-
tions in organic synthesis to produce the β-amino carbonyl compounds [4–9]. In
this perspective, β-amino ketone derivatives have attracted an important attention
due to their broad spectrum of signifcant bioactivities. Furthermore, β-amino
ketone derivatives were extensively used for functionalities including antibacte-
rial, anti-infammatory, analgesic, antidiabetic, antitumor and antimycobacterial
activities. Marketed drugs such as bupropion A-, ondansetron B-, benazepril C-,
lobeline D- and tolperisone hydrochloride- and eperisone hydrochloride E-con-
taining β-amino ketone moiety are widely applied in clinics (Fig. 1). Bupropion
A was used to support discontinuing smoking and to treat major depressive sick-
ness [10, 11]. Ondansetron B was used to avoid vomiting and nausea triggered by
1 3

Ionic liquid‑immobilized proline(s)…
radiation therapy and cancer chemotherapy [12]. Benazepril C was used to treat
heart failure, high blood pressure and diabetic kidney disease [13]. Alpha lobe-
line hydrochloride (lobeline) D is a plant alkaloid that was used to treat asthma
and bronchitis [14]. Eperisone hydrochloride and tolperisone hydrochloride
E were commonly used for relaxation of skeletal and vascular smooth muscle
(antispasmodic) [15]. Compound F contains β-amino carbonyl moiety exhibit-
ing potential androgen receptor antagonists for early control of prostate cancer as
shown in Fig. 1 [16].
Conventionally, the collective principle for the preparation of β-amino car-
bonyl compounds includes three-component Mannich reactions of aldehydes,
−
amines and ketones by [BMIM][BF4 ] [17], heteropoly acids [18], lipases [19],
organobismuth complexes [20], H3PW12O40-supported nanoparticles [21] and
sulfonic nano-silica (SBA-15-Ph-PrSO3H) [22] and polyelectrolyte Brønsted
acid-catalyzed reaction in water medium [23]. The other used methods include
SnTUD-1 [24], salicylate titanocene complexes [25], ionic liquid-immobi-
lized mesoporous silica [26] and ionic liquid polymer in organic solvents [27]
(Scheme 1). Unluckily, most of these approaches are quite sufered from serious
limitations such as longer reaction time, use of metal-supported catalyst, ionic
liquid with other metal cocatalysts, use of toxic solvents, lengthy separation and
problems in recovering and reutilizing catalysts [28–36]. Thus, the improvement
in catalysts for the Mannich reaction in a shorter time is an extremely efective
and supportable method that has fascinated a plentiful consideration in organic
synthesis. In the last decade, task-specifc ionic liquid (TSIL, or functional ionic
liquid) has gained a signifcant attention due to its unambiguous special proper-
ties. Task-specifc ionic liquid (TSIL) or functionalized ionic liquid is used as a
supported catalyst for the synthesis of many heterocyclic biologically active inter-
mediates [37–40]. A careful literature survey reveals that various ionic liquid-
immobilized proline(s) organocatalysts have been reported for asymmetric aldol
and Michael addition reactions. For instance, in 2006, Chan et al. developed an
ionic liquid-immobilized proline(s) and 4-hydroxy proline(s) organocatalyst for
asymmetric aldol reactions [41]. In the same year, Cheng et al. [42] established
various novel functionalized ionic liquid-immobilized proline(s) organocatalysts
for asymmetric Michael addition reactions. In 2008, Zlotin et al. developed task-
specifc ionic liquid-immobilized trans 4-hydroxy l-proline derivatives for asym-
metric aldol reactions in water [43]. In 2009, Trombini et al. developed ionic
liquid-immobilized diphenylprolinol silyl ether for asymmetric Michael addition
reactions [44]. In 2010, Bukuoni et al. synthesized diphenylprolinol silyl ether
organocatalyst for asymmetric Michael addition reactions [45]. In 2011, the same
authors developed C2-symmetric (1R,2R)-bis[(s)-prolinamido]cyclohexane unit-
tagged two imidazolium cations for asymmetric aldol reactions in green media
[46]. In 2012, Headly et al. developed a diarylprolinol silyl ether salt catalyst for
asymmetric Michael addition reactions [47]. In 2013, Headly et al. listed vari-
ous ionic liquid-immobilized proline(s) organocatalysts for asymmetric aldol and
Michael addition reactions [48]. In 2015, Zlotin et al. established C2-symmetric
1 3

M. Prabhakara, B. Maiti
Scheme 1 Mannich reactions: previous and present works
(1,2-diaminoethane-1,2-diyl)bis(N-methylpyridinium)-immobilized two prolina-
mide fragments for asymmetric aldol reactions under neat condition [49]. Ionic
liquid-immobilized proline(s) organocatalysts are environmentally friendly, safe,
cheap and versatile efective catalysts for a wider variety of reactions. Moreo-
ver, very limited ionic liquid-immobilized proline(s) organocatalyst was reported
by researchers and examined for asymmetric aldol and Michael addition reac-
tions. Ionic liquid-immobilized proline(s) organocatalyst could be recycled and
reused several times by simple precipitation methods. Herein, for the frst time
in our laboratory, we synthesized ionic liquid-immobilized proline(s) organocata-
lyst by the modifed procedure [41] and examined for multi-component Mannich
reactions under neat condition. In the last decades, solvent-free reactions have
1 3

Ionic liquid‑immobilized proline(s)…
Scheme 2 Synthesis of alcohol-functionalized ionic liquid 4
Scheme 3 Synthesis of ionic liquid-immobilized l-proline organocatalyst IL-P 7
attracted much attention due to several advantages such as nontoxic due to no sol-
vent, environmentally friendly, safe and economical [50–52]. Herein, we account
for our current improvement in multi-component Mannich reactions by employ-
ing ionic liquid-immobilized proline(s) organocatalyst under solvent-free condi-
tions at a short time.
Results and discussion
Our present synthetic strategy commenced with the synthesis of task-specifc ionic
liquid-immobilized proline(s) moiety. Initially, methylimidazole 1 was reacted with
2-choloethanol 2 at 80 °C for 2 h under solvent-free conditions to obtain the com-
pound [HEMIM][Cl−] 3. Next, compound [HEMIM][Cl−] 3 was reacted with NaBF4
in acetonitrile for 18 h under a refux condition to obtain the hydroxyl-functionalized
−
−
ionic liquid [HEMIM][BF4 ] 4 (Scheme 2). Subsequently, [HEMIM][BF4 ] ionic
liquid 4 was coupled with boc-proline(s) 5 in the presence of DCC/DMAP coupling
1 3

M. Prabhakara, B. Maiti
Table 1 Optimization of the Mannich reaction 11aa
aReaction was performed using 8a (1 mmol), 9a (1 mmol) and 10a (1 mmol) under a solvent-free condi-
tion at room temperature
bYield of the isolated product
reagent in acetonitrile solvent for 24 h in room temperature to provide the ionic liq-
uid-immobilized boc-proline(s) organocatalyst 6.
Afterward, boc moiety was removed by 30% TFA/ACN for 4 h in room tempera-
ture to obtain the fnal ionic liquid-immobilized proline(s) organocatalyst (IL-P) 7
(Scheme 3) [46].
Next, to examine the catalytic activity of ionic liquid-immobilized proline(s)
organocatalyst we used 10 mol% IL-P for multi-component Mannich reactions.
In the preliminary stage of investigation in various solvents, acetophenones 8a,
benzaldehyde 9a and aniline 10a were taken as the model substrates for Man-
nich reactions in the presence of 10 mol% IL-P organocatalyst (Table 1). The ini-
tial screening was performed using 10 mol% IL-P organocatalyst in polar aprotic
solvents such as THF and CH2Cl2 and high-boiling solvents such as DMF and
DMSO for a multi-component Mannich reaction. Using a polar aprotic solvent,
10–20% product yield 11a was observed at room temperature for 24 h (Table 1,
entries 1, 2, 3, 4).
Fascinatingly, the product yield of 11a was dramatically improved to 65%
using a polar aprotic solvent CH3CN for 24 h at room temperature (Table 1, entry
5). By varying the polar protic solvents such as EtOH, IPA and H2O, 60–70%
1 3

Ionic liquid‑immobilized proline(s)…
Mannich base product yield 11a was observed at room temperature for 24 h
(Table 1, entries 6, 7, 8). When performing the same set of reactions under a sol-
vent-free condition at room temperature for 2 h, 96% of the product yield 11a was
obtained (Table 1, entry 9). The Mannich reaction under solvent-free reactions,
using IL-P organocatalyst, at room temperature, at short reaction times, along
with the abolition of side product formation, validates the procedure as an envi-
ronmentally friendly, safe and economical. The obtained Mannich products were
1
characterized by H, 13C NMR and IR spectra. Using 10 mol% IL-P organocata-
lyst for the same set reactions at 80 °C for 3 h under solvent-free conditions, 40%
Mannich base yield 11a was obtained. Hence, heating conditions reduced the
Mannich reaction yield and increased reaction time. Furthermore, for all deriva-
tives, we decided to use it under a solvent-free condition at room temperature.
Our next objective was to examine catalyst loading mol% to get the best catalytic
activity for the multi-component Mannich reactions. We carried out the same set
of Mannich reactions varying 0 to 20 mol% ionic liquid-immobilized proline(s)
organocatalysts. In the absence of IL-P organocatalyst, we did not observe any
Mannich product yield 11a (Table 2, entry 1).
However, using 5 mol% IL-P organocatalyst 85% product yield 11a was
observed in 2 h (Table 2, entry 2). Using 7 mol% of IL-P organocatalyst for
the same set of Mannich reactions, 96% Mannich base yield 11a was obtained
at room temperature for 2 h under solvent-free conditions (Table 2, entry 3).
In the presence of 10–20 mol% IL-P organocatalyst, 96% Mannich base yield
11a was obtained for 2 h. Hence, an increase in organocatalyst mol% did not
Table 2 Optimization of organocatalyst IL-P mol% for Mannich reaction 11aa
aReaction was performed using 8a (1 mmol), 9a (1 mmol) and 10a (1 mmol) under a solvent-free condi-
tion at room temperature
bYield of the isolated product
1 3

M. Prabhakara, B. Maiti
Table 3 The organocatalyst examined in the Mannich reaction 11aa
aReaction was performed using 8a (1 mmol), 9a (1 mmol) and 10a (1 mmol) under a solvent-free condi-
tion at room temperature
bYield of the isolated product
infuence the yield and time for Mannich reactions (Table 2, entries 4, 5, 6).
Therefore, we decided to use 7 mol% IL-P organocatalyst for all derivatives. To
investigate the best organocatalyst for Mannich reactions, we also used 7 mol%
l-proline and 4-hydroxy l-proline organocatalyst. However, in the presence of
7 mol% l-proline and 4-hydroxy l-proline organocatalyst 20–25% product yield
11a was obtained for the Mannich reactions at room temperature for 24 h under
solvent-free conditions. Henceforth, 7 mol% IL-P organocatalyst has shown the
best catalytic activity compared to l-proline and 4-hydroxy l-proline organo-
catalyst (Table 3).
The best catalytic activity of IL-P organocatalyst may be the presence of
ionic liquid moiety immobilized with proline(s) moiety. IL-P organocatalyst has
a synergistic efect that permits the enamine formation with acetophenone very
rapidly and allows imine formation from aromatic aldehyde and amine very ef-
ciently. Simultaneously enamine and imine react to each other by the formation of
Scheme 4 Substrate scope for the synthesis of Mannich base products 11
1 3

Ionic liquid‑immobilized proline(s)…
a carbon–carbon bond to form Mannich bases 11a–11x. Afterward, we assessed
the scope of the Mannich reaction by using electron-donating and electron-with-
drawing substituted acetophenone 8 and substituted aromatic aldehyde 9 and sub-
stituted aromatic amines 10 (Scheme 4) Interestingly, the Mannich product yield
was not afected by the substituent groups on acetophenone, aromatic aldehyde
and aromatic amines. Both the electron-withdrawing and electron-donating sub-
stituents endured an efcient carbon–carbon bond formation reaction smoothly,
resulting in the corresponding Mannich base products 11a–11x with excellent
yields. Moreover, using 2,4-substituted electron-withdrawing acetophenones and
aromatic aldehyde the Mannich reactions took 2 h for completion. For electron-
donating acetophenones and aromatic aldehyde, the Mannich took 3 h for comple-
tion. All these reactions were accomplished under the solvent-free condition in the
presence of 7 mol% IL-P organocatalyst at room temperature in 2–3 h as shown in
Scheme 4.
Substituted acetophenones (R1)
Substituted aromatic aldehydes (R2)
Substituted aromatic amines (R3)
1 3

M. Prabhakara, B. Maiti
Mannich base products:
The plausible mechanistic pathway for the Mannich reaction catalyzed by IL-P
organocatalyst is outlined in Fig. 2. Using IL-P organocatalyst, we expected to
obtain enantioselective Mannich base products but did not obtain any enantiose-
lective Mannich base product 11a–11x. Possibly, the mechanism of the reaction
was progressed via a sequence of reactions such as imine and enamine formation
of acetophenone with IL-P organocatalyst, imine activation by IL-P catalyst and
carbon–carbon bond formation reaction.
1 3

Ionic liquid‑immobilized proline(s)…
Fig. 2 Plausible mechanism and transition state for Mannich reaction using IL-P organocatalyst 7
Initially, the substituted aromatic aldehyde is activated by IL-P organocata-
lyst which reacts with substituted arylamine to provide the intermediate imine
(III). Meanwhile, substituted acetophenone reacts with IL-P organocatalyst to
form imine and enamine (I) and (II). The imine (III) is activated by the IL-P
catalyst and reacts with the enamine (I) and (II) to provide the transition states
(IV) and (V). Possibly, transition states (IV) and (V) are deliberated to be the
rate-determining step. Probably, during the reaction of acetophenones with IL-P
organocatalyst phenyl ring of acetophenone and proline moiety will arrange in a
perpendicular plane to avoid the steric hindrance. Therefore, enamine formations
(I) and (II) are possible. Next, transition states IV and V will have equal energy
which leads to re- and si-face attack of enamine of acetophenone (I) and (II) with
1 3

M. Prabhakara, B. Maiti
imine (III) by the formation of the carbon–carbon bond. Furthermore, using IL-P
organocatalyst racemic Mannich base products 11a–11x were obtained in a high
yield with a short time.
The recycling performance test of the IL-P organocatalyst is investigated in
Fig. 3. After the Mannich reaction under a solvent-free condition for a short time,
Mannich base product was precipitated with ether and decanted in another beaker.
Since IL-P organocatalyst is very polar and viscous, it sticks to the wall of the
reaction vessel. The reaction vessel was washed with dichloromethane, and the
same set of reactions was carried out fve times. The IL-P organocatalyst activity
was almost the same without an appreciable decrease in yield.
Summary
In summary, a highly efcient ionic liquid-immobilized proline(s) organocata-
lyst (IL-P)-catalyzed Mannich reaction was investigated. The IL-P organocatalyst
had shown higher catalytic activity under solvent-free conditions at short reac-
tion times to provide Mannich base with a high yield The salient features of this
strategy include high-atom economy, milder reaction conditions, inexpensive
metal-free organocatalyst, shorter reaction time and without chromatographic
purifcation. The IL-P organocatalyst was recycled and reused fve times without
a signifcant loss of its catalytic activity.
Fig. 3 Recycling test of IL-P organocatalyst-catalyzed Mannich reaction at the neat condition
1 3

Ionic liquid‑immobilized proline(s)…
Experimental section
Methylimidazole, 2-chloroethanol, l-proline, 4-hydroxy l-proline, acetonitrile
(HPLC grade), ethyl acetate, anhydrous sodium sulfate and all substrates for ace-
tophenone, aromatic aldehydes and aromatic amine derivatives were purchased
from Sigma-Aldrich and used without further purifcation. All solvents were
obtained from commercial sources. All chemicals were purchased from Sigma-
Aldrich. All reactions were performed under an open atmosphere with unpuri-
fed reagents and dry solvents. Analytical thin-layer chromatography (TLC) was
1
performed using 0.25-mm silica gel-coated Kieselgel 60 F254 plates. H NMR
(400 MHz) and 13C NMR (100 MHz) spectra were recorded on a Bruker DRX-
400 spectrometer. Chemical shifts were reported in parts per million from tetra-
methylsilane (TMS) with the solvent resonance as the internal standard (CHCl3:
δ = 7.26 ppm). The pattern of reported data is as follows: chemical shifts, mul-
tiplicity (s = singlet, d = doublet, dd = double doublet, t = triplet, q = quartet,
br = broad, m = multiplet), integration and coupling constants (Hz). 13C NMR
spectra were recorded at 100 MHz with proton decoupling. Chemical shifts
were reported in parts per million from TMS with the solvent resonance as the
internal standard (CHCl3: δ 77.0 ppm). IR spectra were obtained using the FTIR
spectrometer. Racemic compounds were determined by chiral HPLC equipped
with a Chiralpak IC (250 × 4.6 mm) analytical column.
General procedure for the synthesis of alcohol‑functionalized ionic liquid (IL) 4
Methylimidazole 1a (1.0 g, 12.2 mmol, 1 equiv) and 2-chloroethanol (0.975 g,
12.2 mmol, 1 equiv) were taken in a 100-mL round-bottom fask and heated
at 80 °C for 2 h under neat condition. After the reaction, mixture was cooled
to ambient temperature; the viscous solid was successively washed with ether
(20 mL × 3) and then dried under vacuum for 6 h. The hydroxyl-functionalized
1
ionic liquid 3 [HEMIM][Cl−] was obtained as white crystals (1.85 g, 94%). H
NMR (400 MHz, DMSO-d6) δ 8.79 (s, 1H), 7.59 (t, J = 1.6, Hz, 1H), 7.54 (t,
J = 1.6 Hz, 1H), 4.40 (t, J = 5.0 Hz, 2H), 4.01 (t, J = 5.0 Hz, 2H), 3.99 (s, 1H).
13C NMR (100 MHz, DMSO-d6) δ 137.3, 123.7, 123.1, 59.7, 51.9, 36.1.
In a 100-mL round-bottom fask, ionic liquid [HEMIM][Cl−] (1.85 g,
11.4 mmol, 1 equiv) 3 in dry 25 mL acetonitrile NaBF4 (1.4 g, 13.7 mmol, 1.2
equiv) was added and stirred at room temperature for 18 h under nitrogen atmos-
phere. The so-formed white precipitate was fltered of and washed with acetoni-
trile (30 mL × 3). Concentration of combined fltrates provides hydroxyl-func-
−
tionalized ionic liquid [HEMIM][BF4 ] product 4 as light yellow oil (2.32 g,
1
95%). H NMR (400 MHz, D2O) δ 9.38 (s, 1H), 7.83 (t, J = 1.5, Hz, 1H), 7.80
(t, J = 1.5 Hz, 1H), 5.58 (brs, 1H), 4.26 (t, J = 4.9 Hz, 2H), 3.88 (s, 1H), 3.69 (t,
J = 4.9 Hz, 2H). 13C NMR (100 MHz, D2O) δ 136.4, 123.6, 122.5, 59.9, 51.6,
35.7. FTIR (KBr, cm−1): 3549, 3163, 1572, 1014. MS (FAB): m/z 127 (M+).
1 3

M. Prabhakara, B. Maiti
General procedure for the synthesis of ionic liquid‑supported l‑boc‑proline 6
To a mixture of alcohol ionic liquid (1.5 g, 7.0 mmol, 1 equiv) 4, l-boc-proline
(1.48 g, 7.0 mmol, 1 equiv) and dimethylaminopyridine catalytic amount, in
30 mL dry acetonitrile solvent dicyclohexylcarbodiimide (1.8 g, 8.7 mmol, 1.2
equiv) was added in CH2Cl2 (5 mL) dropwise for 5 min. Afterward, the reaction
mixture was vigorously stirred for 24 h in room temperature. After completion
of the reaction, the reaction mixture was fltered through Celite plug. The fltrate
was concentrated under vacuum, and the coupled product was washed with ether
and CH2Cl2 for two–three times. The crude mixture 6 was dried under high vac-
1
uum and formed viscous solid (2.7 g, 96%) characterized by NMR and IR. H
NMR (400 MHz, DMSO-d6) δ 9.13 (d, J = 9.4 Hz, 1H), 7.76 (s, 1H), 7.72 (s, 1H),
4.52- 4.38 (m, 4H), 4.19–4.13 (m, 1H), 3.87 (s, 3H), 3.38 (dd, J = 14.0, 7.0 Hz,
2H), 2.24–2.12 (m, 1H), 1.84–1.74 (m, 3H), 1.38 (s, 3H), 1.25(s, 6H). 13C NMR
(100 MHz, DMSO-d6) δ 170.6 (d, JCF= 26 Hz), 152.01, 135.5(d, JCF= 5 Hz),
122.1(d, JCF= 5 Hz), 121.0(d, JCF= 5 Hz), 77.4 (d, JCF= 21 Hz), 63.35, 61.1(d,
JCF= 32 Hz), 56.8 (d, JCF= 24 Hz), 46.3(d, JCF= 19 Hz), 44.6 (d, JCF= 24 Hz),
27.8, 26.3 (d, JCF= 29 Hz), 22.3, 21.6. FTIR (KBr, cm−1) 3609, 3157, 2978, 1747,
1682, 1049, 1034.
General procedure for the synthesis of ionic liquid‑supported l‑proline IL‑P 7
To a mixture of alcohol ionic liquid-immobilized l-boc-proline (2.7 g, 6.57 mmol),
in dry acetonitrile solvent 30 mL of 30% TFA/ACN was added. After that, the reac-
tion mixture was vigorously stirred for 4 h in room temperature. The fltrate was
concentrated under vacuum, washed with ether and CH2Cl2 for two–three times,
dried under high vacuum to get the pure product (2.1 g, 95%) and characterized by
NMR, IR and MS analysis. 1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 7.78 (s,
1H), 7.70 (s, 1H), 4.42 (t, J=7.3 Hz, 2H), 4.27–4.19 (m, 1H), 3.87 (s, 3H), 3.72 (t,
J=5.2 Hz, 1H). 3.24 (d, J=3.3 Hz, 2H), 2.50 (d, J=1.5 Hz, 1H), 2.30–2.22 (m,
1H), 1.99–1.88 (m, 4H). 13C NMR (100 MHz, DMSO-d6) δ 166.9, 135.7, 122.1,
121.2, 62.5, 67.1, 46.2, 44.0, 34.2, 26.1, 21.5. FTIR (KBr, cm−1) 3454, 3167, 1738,
20
1670, 1165, 1138, 1055, 1036. MS (GC): m/z 224 (M+). [α] +32 (0.2, H2O).
D =
General procedure for the synthesis of β‑amino ketone 11a
To a 50-mL RB fask, acetophenone (0.3 g, 2.5 mmol, 1 equiv) 8a, benzaldehyde
(0.26 g, 2.5 mmol, 1 equiv) 9a, aniline (0.23 g, 2.5 mmol, 1 equiv) 10a and 7 mol%
IL-P organocatalyst 7 were added and stirred at room temperature for 2 h under
a solvent-free condition. The solid product formed after 2 h. The progress of the
reaction was monitored by TLC. After the completion of the reaction, the reaction
mixture was precipitated with ether and decanted in an another beaker. The solid
product was washed with ether (10 mL×2) and hexane (10 mL×2) to get the pure
1 3

Ionic liquid‑immobilized proline(s)…
1
product (0.74 g, 96%). The obtained solid products were characterized by H, 13C
NMR and IR spectra.
1,3‑Diphenyl‑3‑(phenylamino)propan‑1‑one 11a22, 25 White solid. Yield: 97%;
MP: 154–155 °C; FTIR (KBr, cm−1): 3333, 1668, 684, 1H NMR (400 MHz, CDCl3)
δ 7.94 (d, J=7.5 Hz, 2H), 7.59 (t, J=7.3 Hz, 1H), 7.47 (m, 4H), 7.36 (t, J=7.4 Hz,
2H), 7.26 (t, J=7.2 Hz, 1H), 7.12 (t, J=7.7 Hz, 2H), 6.69 (t, J=7.2 Hz, 1H), 6.59
(d, J=8.2 Hz, 2H), 5.04 (dd, J=7.4, 5.4 Hz, 1H), 3.54 (dd, J=16.1, 5.2 Hz, 1H),
3.45 (dd, J=16.1, 7.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.3, 147.0, 143.0,
136.7, 133.5, 129.1, 128.9, 128.7, 128.2, 127.4, 126.4, 117.8, 113.8, 54.8, 46.3.
3((4‑Chlorophenyl)amino)‑1‑3‑diphenylpropan‑1‑one 11b25 White solid.
1
Yield: 94%. MP: 148–149 °C. FTIR (KBr, cm−1): 3369, 1662, 681. H NMR
(400 MHz, CDCl3) δ 7.92 (d, J=7.4 Hz, 2H), 7.59 (t, J=7.4 Hz, 1H), 7.49– 7.43
(m, 4H), 7.35 (t, J=7.3 Hz, 2H), 7.27 (d, J=7.3 Hz, 1H), 7.04 (d, J=8.8 Hz, 2H),
6.50 (d, J=8.8 Hz, 2H), 4.98 (dd, J=7.5, 5.0 Hz, 1H), 3.51 (dd, J=16.2, 4.9 Hz,
1H), 3.43 (dd, J=16.2, 7.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.2, 145.6,
142.5, 136.6, 133.6, 128.9, 128.8, 128.6, 128.2, 127.5, 126.3, 122.4, 115.0, 54.9,
46.2.
3‑((2‑Chlorophenyl)amino)‑1‑3‑diphenylpropan‑1‑one 11c25 White solid.
1
Yield: 95%. MP: 110–111 °C. FTIR (KBr, cm−1): 3394, 1680, 681. H NMR
(400 MHz, CDCl3) δ 7.94 (d, J=7.3 Hz, 2H), 7.59 (t, J=7.4 Hz, 1H), 7.47 (t,
J=8.0 Hz, 4H), 7.36 (t, J=7.3 Hz, 2H), 7.25 (dd, J=7.8, 1.2 Hz, 1H), 7.03–6.98
(m, 1H), 6.63–6.59 (m, 1H), 6.54 (d, J=8.2 Hz, 1H), 5.13 (t, J=6.4 Hz, 1H), 3.55
(d, J=6.2 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 197.8, 142.8, 142.4, 136.7,
133.5, 129.1, 128.9, 128.7, 128.2, 127.6, 127.5, 126.3, 119.6, 117.7, 112.7, 54.5,
46.4.
3‑((3‑Chlorophenyl)amino)‑1‑3‑diphenylpropan‑1‑one 11d28 White solid.
1
Yield: 95%. MP 110–111 °C. FTIR (KBr, cm−1): 3395, 1680, 688. H NMR
(400 MHz, CDCl3) δ 7.97–7.93 (m, 2H), 7.60 (t, J=1.1 Hz, 1H), 7.59 (s, 1H), 7.57
(t, J=1.1 Hz, 1H), 7.49–7.42 (m, 4H), 7.37–7.33 (m, 2H), 7.28–7.24 (m, 2H), 6.61
(td, J=7.7, 1.4 Hz, 1H), 6.54 (dd, J=8.1, 1.2 Hz, 1H), 5.17–5, 12 (m, 1H), 3.55 (d,
J=6.1 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 197.8, 142.8, 142.4, 136.7, 133.5,
129.1, 128.9, 128.7, 128.2, 127.6, 127.5, 126.3, 119.6, 117.7, 112.7, 54.5, 46.5.
1,3‑Diphenyl‑3‑(m‑tolylamino)propan‑1‑one 11e25 White solid. Yield: 96%.
MP 126-127 °C. FTIR (KBr, cm−1): 3385, 1665, 687. 1H NMR (400 MHz, CDCl3)
δ 7.94 (d, J=7.5 Hz, 2H), 7.59 (t, J=7.5 Hz, 1H), 7.49–7.44 (m, 4H), 7.35 (t,
J=7.4 Hz, 2H), 7.28–7.23 (m, 1H), 7.00 (t, J=7.8 Hz, 1H), 6.52 (d, J=7.4 Hz,
1H), 6.44 (s, 1H), 6.38 (d, J=8.0 Hz, 1H), 5.03 (dd, J=7.3, 5.6 Hz, 1H), 3.56
(dd, J=16.1, 5.2 Hz, 1H), 3.45 (dd, J=16.1, 7.6 Hz, 1H), 2.23 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 198.3, 147.0, 143.1, 138.9, 136.7, 133.4, 129.0, 128.9, 128.7,
128.2, 127.3, 126.4, 119.8, 114.7, 110.8, 54.8, 46.3, 21.6.
1 3

M. Prabhakara, B. Maiti
1,3‑Diphenyl‑3‑(p‑tolylamino)propan‑1‑one 11f22,25 White solid. Yield:
1
96%. MP: 138–139 °C. FTIR (KBr, cm−1): 3400, 1678, 800. H NMR (400 MHz,
CDCl3) δ 7.96 (d, J=7.2 Hz, 2 H), 7.63 (t, J=7.3 Hz, 1H), 7.52 (t, J=7.8 Hz, 2H),
7.44 (d, J=7.24 Hz, 2H), 7.28 (t, J=7.4 Hz, 2H), 7.17 (t, J=7.3 Hz, 1H), 6.79
(d, J=8.2 Hz, 2H), 6.42 (d, J=8.4 Hz, 2H), 4.97 (dd, J=8.4, 4.6 Hz, 1H), 3.62
(dd, J=16.8, 8.7 Hz, 1H), 3.29 (dd, J=16.8, 4.7 Hz, 1H), 2.08 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 197.9, 145.9, 144.6, 137.3, 133.6, 129.6, 129.2, 128.7, 128.5,
127.1, 124.7, 113.6, 79.6, 53.7, 46.4, 20.5.
3‑((4‑Nitrophenyl)amino)‑1,3‑diphenylpropan‑1‑one 11g28 Pale yellow solid.
1
Yield: 97%. MP: 162–163 °C. FTIR (KBr, cm−1): 3366, 1684, 1291. H NMR
(400 MHz, CDCl3) δ 8.02 (d, J=9.1 Hz, 2H), 7.91 (d, J=7.5 Hz, 2H), 7.60 (t,
J=7.4 Hz, 1H), 7.47 (t, J=7.8 Hz, 2H), 7.44–7.34 (m, 4H), 7.30–7.26 (m, 1H),
6.53 (d, J=9.1 Hz, 2H), 5.13 (t, J=5.4 Hz, 1H), 3.55 (d, J=6.2 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ 197.89, 152.19, 141.13, 138.49, 136.36, 133.84, 129.16,
128.84, 128.21, 127.96, 126.19, 126.15, 112.22, 54.34, 45.53.
3‑((4‑Methoxyphenyl)amino)‑1,3‑diphenylpropan‑1‑one 11h25 Gray solid.
Yield: 96%. MP: 136–137 °C. FTIR (KBr, cm−1): 3369, 1662, 1510, 810. 1H NMR
(400 MHz, CDCl3) δ 7.94 (d, J=7.4 Hz, 2H), 7.58 (t, J=7.5 Hz, 1H), 7.47 (dd,
J=7.7, 6.6 Hz, 4H), 7.35 (t, J=7.3 Hz, 2H), 7.25 (t, J=7.4 Hz, 1H), 6.71 (dd,
J=8.9, 2 Hz, 2H), 6.56 (d, J=8.9 Hz, 2H), 4.95 (dd, J=7.6, 5.2 Hz, 1H), 3.71
(s, 3H), 3.51 (dd, J=16.2, 5.1 Hz, 1H), 3.43 (dd, J=16.2, 7.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3) δ 198.4, 152.4, 143.2, 141.1, 136.7, 133.4, 128.8, 128.7, 128.2,
127.3, 126.5, 115.4, 114.7, 55.8, 55.7, 46.4.
1‑Phenyl‑3‑(phenylamino)‑3‑(p‑tolyl)propan‑1‑one 11i29 Gray solid. Yield:
94%. MP: 122–123 °C. FTIR (KBr, cm−1): 3385, 1664, 1286. 1H NMR (400 MHz,
CDCl3) δ 7.95 (d, J=7.4 Hz, 2H), 7.59 (t, J=7.4 Hz, 1H), 7.47 (t, J=7.8 Hz,
2H), 7.36 (d, J=8.0 Hz, 2H), 7.17–7.09 (m, 4H), 6.68 (t, J=7.3 Hz, 1H), 6.59
(d, J=8.0 Hz, 2H), 5.01 (dd, J=7.4, 5.5 Hz, 1H), 3.53(dd, J=16.1, 5.3 Hz, 1H)
3.43 (dd, J=16.1, 7.6 Hz, 1H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 198.4,
147.1, 139.9, 136.9, 136.7, 133.4, 129.5, 129.1, 128.7, 128.2, 126.3, 117.7, 113.8,
54.5, 46.4, 21.1.
1‑Phenyl‑3‑(p‑tolyl)‑3‑(p‑tolylamino) propan‑1‑one 11j30 White solid. Yield:
1
95%. MP 140–141 °C. FTIR (KBr, cm−1): 3385, 1670, 1517, 1286.5, 798.5. H
NMR (400 MHz, CDCl3) δ 7.94 (d, J=7.2, 2H), 7.59 (t, J=7.4 Hz, 1H), 7.47
(t, J=7.8 Hz, 2H), 7.35 (d, J=8.0 Hz, 2H), 7.16 (d, J=7.8 Hz, 2H), 6.93 (d,
J=8.0 Hz, 2H), 6.51 (d, J=8.3 Hz, 2H), 4.98 (dd, J=7.2, 5.8 Hz, 1H), 3.54 (dd,
J=16.1, 5.3 Hz, 1H) 3.44 (dd, J=16.1, 7.6 Hz, 1H), 2.34 (s, 3H), 2.21 (s, 3H). 13
C
NMR (100 MHz, CDCl3) δ 198.5, 144.8, 140.1, 136.9, 136.8, 136.4, 129.6, 129.5,
128.7, 128.2, 126.9, 126.3, 114.0, 54.8, 46.5, 21.1, 20.4.
1 3

Ionic liquid‑immobilized proline(s)…
3‑((4‑Methoxyphenyl)amino)‑1‑phenyl‑3‑(p‑tolyl)propan‑1‑one 11 k31 Gray
solid. Yield: 98%. MP 120–121 °C. FTIR (KBr, cm−1): 3391, 1668, 1512, 1236,
813. 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J=7.4 Hz, 2H), 7.59 (t, J=7.4 Hz, 1H),
7.47 (t, J=7.7 Hz, 2H), 7.35 (d, J=7.9 Hz, 2H), 7.15 (d, J=7.8 Hz, 2H), 6.71 (d,
J=8.9 Hz, 2H), 6.56 (d, J=8.9 Hz, 2H), 4.92 (dd, J=7.5, 6.4 Hz, 1H), 3.71 (s, 3H),
3.52 (dd, J=16.2, 5.2 Hz, 1H), 3.48 (dd, J=16.2, 7.7 Hz, 1H), 2.34 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 128.5, 152.3, 141.3, 140.2, 136.9, 136.8, 133.4, 129.5,
128.7, 128.2, 126.4, 115.4, 114.7, 55.7, 55.4, 46.5, 21.1.
3‑(4‑Methox yphenyl)‑1‑phenyl‑3‑(phenylamino)propan‑1‑ one
11l22, 25 White solid, Yield: 96%. MP: 137–138 °C. FTIR (KBr, cm−1): 3391,
1
1668, 1512, 814. H NMR (400 MHz, CDCl3) δ 7.96–7.92 (d, J=7.3, 2H), 7.59 (t,
J=7.4 Hz, 1H), 7.47 (t, J=7.7 Hz, 2H), 7.38 (d, J=8.6 Hz, 2H), 7.12 (t, J=7.9 Hz,
2H), 6.88 (d, J=8.7 Hz, 2H), 6.69 (t, J=7.3 Hz, 1H), 6.60 (d, J=7.8 Hz, 2H),
4.99 (t, J=7.1 1H), 3.79 (s, 3H), 3.52 (dd, J=16.1, 5.5 Hz, 1H), 3.43 (dd, J=16.1,
7.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 198.46, 158.81, 146.95, 136.75,
134.87, 133.42, 129.13, 128.71, 128.23, 127.51, 117.83, 114.29, 113.92, 55.27,
54.30, 46.31.
3‑(4‑Methoxyphenyl)‑ 1‑phenyl‑3‑(p‑tolylamino)propan‑1‑one 11m25 White
solid. Yield: 95%. MP: 154–155 °C. FTIR (KBr, cm−1): 3385, 1668, 1512, 798.
1H NMR (400 MHz, CDCl3) δ 7.92 (d, J=7.5 Hz, 2H), 7.58 (t, J=7.3 Hz, 1H),
7.46 (t, J=7.3 Hz, 2H), 7.37 (d, J=7.4 Hz, 2H), 6.93 (d, J=7.5 Hz, 2H), 6.87 (d,
J=7.4 Hz, 2H), 6.52 (d, J=7.2 Hz, 2H), 4.96 (t, J=6.2 Hz, 1H), 3.79 (s, 3H), 3.50
(dd, J=15.9, 5.2 Hz, 1H), 3.42 (dd, J=15.8, 7.2 Hz, 1H), 2.21 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 198.5, 158.8, 144.8, 136.9, 135.2, 133.3, 129.8, 129.6, 128.6,
128.6, 128.2, 127.5, 127.0, 114.2, 114.1, 55.3, 54.5, 46.4, 20.4.
3‑(3‑Hydroxyphenyl)‑1‑phenyl‑3‑(phenylamino)propan‑1‑one 11n32 Light
green solid. Yield: 95%. MP 134–135 °C. FTIR (KBr, cm−1): 3323, 1649, 1601,
1570, 684. 1H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H), 7.96 (d, J=7.2, 2H), 7.64 (t,
J=7.4 Hz, 1H), 7.53 (t, J=7.6 Hz, 2H), 7.08 (t, J=7.8 Hz, 1H), 6.98 (t, J=7.8 Hz,
2H), 6.87–6.84 (m, 2H), 6.58 (dd, J=8.0, 1.8 Hz, 1H), 6.49–6.44 (m, 2H), 6.16
(d, J=7.3 Hz, 1H), 4.89 (dd, J=11.7, 8.3 Hz, 1H), 3.60 (dd, J=16.9, 8.9 Hz, 1H),
3.25 (dd, J=16.9, 4.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 197.8, 157.8, 148.4,
146.2, 137.3, 133.6, 129.8, 129.2, 128.5, 117.7, 116.2, 114.2, 113.8, 113.2, 79.6,
53.3, 46.9.
25
3‑(4‑Chlorophenyl)‑1‑phenyl‑3‑(phenylamino)propan‑1‑one 11o22,
Light
green solid. Yield: 96%. MP 106–107 °C. FTIR (KBr, cm−1): 3390, 1666, 1284,
1
780. H NMR (400 MHz, CDCl3) δ 7.92 (d, J=7.1 Hz, 2H), 7.60 (t, J=7.4 Hz,
1H), 7.48 (t, J=7.7 Hz, 2H), 7.41 (d, J=8.4 Hz, 2H), 7.32–7.28 (m, 2H), 7.12 (dd,
J=8.5, 7.4 Hz, 2H), 6.71 (t, J=7.3 Hz, 1H), 6.56 (d, J=7.7, 2H), 5.0 (dd, J=7.0,
5.8, 1H), 3.50 (dd, J=16.2, 6.2 Hz, 1H), 3.44 (dd, J=9.0, 7.3 Hz, 1H)). 13C NMR
1 3

M. Prabhakara, B. Maiti
(100 MHz, CDCl3) δ 197.9, 146.7, 141.5, 136.6, 133.6, 133.0, 129.2, 129.0, 128.8,
128.2, 127.8, 118.1, 113.8, 54.2, 46.1.
3‑(2‑Chlorophenyl)‑3‑((4‑chlorophenyl)amino)‑1‑phenylpropan‑1‑one
11p34 Gray solid. Yield: 95%. MP 110–111 °C. FTIR (KBr, cm−1): 3392, 1678,
746. 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J=7.2 Hz, 2H), 7.60 (t, J=7.4 Hz, 1H),
7.51–7.45 (m, 2H), 7.47 (d, J=7.5 Hz, 1H), 7.45–7.40 (m, 1H), 7.21 (dd, J=5.6,
3.5 Hz, 2H), 7.03 (d, J=8.9 Hz, 2H), 6.41 (d, J=8.8 Hz, 2H), 5.28 (dd, J=8.6,
3.7 Hz, 1H), 3.61 (dd, J=15.7, 3.8 Hz, 1H), 3.33 (dd, J=15.8, 8.6 Hz, 1H). 13C
NMR (100 MHz, CDCl3) δ 198.5, 145.1, 139.0, 136.4, 133.7, 132.4, 129.9, 129.0,
128.8, 128.3, 127.9, 127.5, 122.6, 114.7, 52.1, 43.5.
3‑((3‑Chlorophenyl)amino)‑3‑(4‑nitrophenyl)‑1‑phenylpropan‑1‑one
11q33 White solid. Yield: 96%. MP 158–160 °C. FTIR (KBr, cm−1): 3402, 1670,
1
1597, 1512, 684. H NMR (400 MHz, CDCl3) δ 8.12 (d, J=8.7 Hz, 2H), 7.82
(d, J=7.3, 2H), 7.53 (dd, J=12.1, 8.1 Hz, 3H), 7.39 (t, J=7.9 Hz, 2H), 6.94 (t,
J=8.1 Hz, 1H), 6.60 (dd, J=7.9, 1.2 Hz, 1H), 6.43 (t, J=2.0 Hz, 1H), 6.32 (dd,
J=8.1, 2.0 Hz, 1H), 5.00 (t, J=6.1 Hz, 1H), 3.42 (d, J=6.1 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ 197.1, 150.0, 147.5, 147.4, 136.2, 135.0, 133.9, 130.3, 129.0,
128.1, 127.4, 124.2, 118.5, 113.6, 112.0, 77.3, 77.2, 77.01, 76.70, 54.09, 45.44.
1‑(4‑Hydroxyphenyl)‑3‑phenyl‑3‑(phenylamino)propan‑1‑one 11r314 White
solid. Yield: 97%. MP 130–132 °C. FTIR (KBr, cm−1): 3309, 1668, 684. H NMR
(400 MHz, CDCl3) δ 10.37 (s, 1H), 7.84 (d, J=8.6 Hz, 2H), 7.44 (d, J=7.5 Hz,
2H), 7.28 (t, J=7.5 Hz, 2H), 7.17 (t, J=7.3 Hz, 1H), 6.97 (t, J=7.7 Hz, 2H), 6.84
(d, J=8.6 Hz, 2H), 6.50–6.43 (m, 2H), 6.18 (d, J=7.7 Hz, 1H), 4.97 (dd, J=12.6,
8.0 Hz, 1H), 3.52 (dd, J=16.5, 8.6 Hz, 1H), 3.17 (dd, J=16.5, 4.6 Hz, 1H). 13C
NMR (100 MHz, CDCl3) δ 195.8, 162.5, 148.3, 144.6, 131.2, 131.1, 129.3, 129.2,
128.9, 128.7, 127.1, 116.2, 115.6, 114.3, 113.2, 79.6, 53.5, 40.6.
3‑((4‑Chlorophenyl)amino)‑3‑phenyl‑1‑(p‑tolyl)propan‑1‑one 11s35 White
1
solid. Yield: 96%. MP 110–111 °C. FTIR (KBr, cm−1): 3387, 1662, 1288, 806. H
NMR (400 MHz, CDCl3) δ 7.72 (d, J=8.0 Hz, 2H), 7.33 (d, J=7.6 Hz, 2H), 7.24
(t, J=7.5 Hz, 2H), 7.16 (dd, J=7.3, 3.0 Hz, 3H), 6.93 (d, J=8.7 Hz, 2H), 6.39
(d, J=8.7 Hz, 2H), 4.84 (dd, J=7.7, 4.9 Hz, 1H), 3.39 (dd, J=16.2, 4.8 Hz, 1H),
3.29 (dd, J=16.1, 7.9 Hz, 1H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 197.8,
145.6, 144.5, 142.5, 134.1, 130.2, 129.4, 129.1, 128.9, 128.4, 127.5, 126.3, 122.4,
116.3, 115.0, 55.1, 46.1, 21.7.
3‑Phenyl‑3‑(phenylamino)‑1‑(p‑tolyl)propan‑1‑one 11t22,25 Gray
solid.
1
Yield: 94%. MP 120–122 °C. FTIR (KBr, cm−1): 3379, 1660, 1288, 742. H
NMR (400 MHz, CDCl3) δ 7.84 (d, J=8.0 Hz, 2H), 7.47 (d, J=7.7 Hz, 2H), 7.35
(t, J=7.3 Hz, 2H), 7.27 (d, J=7.6 Hz, 3H), 7.11 (t, J=7.7 Hz, 2H), 6.70 (dd,
J=16.3, 8.9 Hz, 1H), 6.59 (d, J=7.9 Hz, 1H), 5.01 (dd, J=7.3, 5.4 Hz, 1H), 3.51
(dd, J=16.0, 5.1 Hz, 1H), 3.41 (dd, J=16.0, 7.8 Hz, 1H), 2.44 (s, 3H). 13C NMR
1 3

Ionic liquid‑immobilized proline(s)…
(100 MHz, CDCl3) δ 197.9, 144.4, 143.0, 134.2, 129.4, 129.1, 128.8, 127.3, 126.4,
117.8, 113.9, 55.0, 46.2, 21.7.
1‑(4‑Methoxyphenyl)‑3‑phenyl‑3‑(phenylamino)propan‑1‑one 11u29 Light
green solid. Yield: 96%. MP 115–117 °C. FTIR (KBr, cm−1): 3379, 1655, 1597,
1
1257. H NMR (400 MHz, CDCl3) δ 7.93 (d, J=8.8 Hz, 2H), 7.48 (d, J=7.4 Hz,
2H), 7.35 (t, J=7.5 Hz, 2H), 7.27 (d, J=8.6 Hz, 1H), 7.11 (t, J=7.8 Hz, 2H), 6.94
(d, J=8.8 Hz, 2H), 6.68 (t, J=7.3 Hz, 1H), 6.59 (d, J=7.8 Hz, 2H), 5.0 (dd, J=7.5,
5.2 Hz, 1H), 3.89 (s, 3H), 4.8 (dd, J=15.8, 4.9 Hz, 1H), 3.38 (dd, J=15.8, 7.8 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ 196.8, 163.8, 147.1, 143.2, 130.6, 129.8, 129.1,
128.8, 127.3, 126.4, 117.7, 113.8, 113.8, 55.5, 55.0, 46.0.
1‑(4‑Chlorophenyl)‑3‑phenyl‑3‑(phenylamino)propan‑1‑one
11v36 Light
1
blue solid. Yield: 96%. MP 130–132 °C. FTIR (KBr, cm−1): 3367, 1678, 1280. H
NMR (400 MHz, CDCl3) δ 7.85 (d, J=8.5 Hz, 2H), 7.44 (t, J=7.5 Hz, 4H), 7.35
(t, J=7.5 Hz, 2H), 7.27 (d, J=8.6, 1H), 7.12 (t, J=7.8 Hz, 2H), 6.70 (t, J=7.3 Hz,
1H), 6.59 (d, J=8.1 Hz, 2H), 5.03 (t, J=6.3 Hz, 1H), 3.54–3.39 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ 197.1, 146.8, 142.7, 139.9, 135.1, 129.9, 129.6, 129.3, 129.2,
129.0, 128.8, 128.5, 127.5, 126.4, 117.9, 115.1, 113.8, 77.3, 77.0, 76.7, 54.8, 46.2.
1‑(2‑Nitrophenyl)‑3‑phenyl‑3‑(phenylamino)propan‑1‑one
11w Yellow
solid. Yield: 97%. MP 150–152 °C. FTIR (KBr, cm−1): 3385, 1668, 1597, 1288.
1H NMR (400 MHz, CDCl3) δ 7.94 (d, J=8.2 Hz, 1H), 7.59 (t, J=7.4 Hz, 1H),
7.48 (dd, J=10.4, 3.4 Hz, 2H), 7.36 (t, J=7.5 Hz, 1H), 7.29–7.23 (m, 1H), 7.12
(t, J=7.7 Hz, 1H), 6.69 (t, J=7.3 Hz, 1H), 6.60 (d, J=8.2 Hz, 1H), 5.07–5.02 (t,
J=6.8 Hz, 1H), 3.58–3.42 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 198.3, 147.0,
143.0, 136.7, 133.5, 129.3, 129.1, 128.8, 128.7, 128.6, 128.9, 128.3, 128.2, 127.4,
126.4, 117.8, 115.1, 113.8, 54.8, 46.3.
1‑(3‑Nitrophenyl)‑3‑phenyl‑3‑(phenylamino)propan‑1‑one 11x Yellow solid.
Yield: 96%. MP 160–162 °C. FTIR (KBr, cm−1): 3398, 1691, 1600, 1519. 1H NMR
(400 MHz, CDCl3) δ 8.70 (s, 1H), 8.22 (d, J=7.7 Hz, 1H), 7.66 (t, J=8.0 Hz, 1H),
7.46 (d, J=7.6 Hz, 2H), 7.35 (t, J=7.5 Hz, 2H), 7.27 (dd, J=12.8, 5.5 Hz, 1H),
7.14 (t, J=7.9 Hz, 2H), 6.71 (t, J=6.9 Hz, 1H), 6.62 (d, J=8.0 Hz, 2H), 5.09 (t,
J=6.2 Hz, 1H), 3.57 (d, J=6.1 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 196.2,
148.4, 146.6, 142.3, 137.9, 133.6, 130.0, 129.3, 129.2, 129.2, 128.9, 128.8, 127.7,
127.6, 126.3, 123.1, 118.1, 113.8, 64.0, 46.3.
Supporting information
The Supporting Information is available free of charge on the Website spinger.com.
1
Analytical data H, 13C NMR and IR spectra of 11a–11x were provided in SI
page nos. 2–49, and analytical data of IL-P organocatalysts and HPLC data provided
in SI page nos. 50–63.
1 3

M. Prabhakara, B. Maiti
Acknowledgements The authors thank DST, Government of India, for funding through DST-SERB-
YSS/2015/000450, thank the Chancellor and Vice-Chancellor of VIT for providing an opportunity to
carry out this study and further thank the management of VIT for providing seed money as a research
grant.
References
1. G. Dagousset, F. Drouet, G. Masson, J. Zhu, Org. Lett. 11, 5546 (2009)
2. C. Ayats, A.H. Henseler, E. Dibello, M.A. Pericàs, ACS Catal. 4, 3027 (2014)
3. Y. Luan, J. Yu, X. Zhang, S.E. Schaus, G. Wang, J. Org. Chem. 79, 4694 (2014)
4. N. Isambert, M.M.S. Duque, J.C. Plaquevent, Y. Genisson, J. Rodriguez, T. Constantieux, Chem.
Soc. Rev. 40, 1347 (2011)
5. A. Dömling, W. Wang, K. Wang, Chem. Rev. 112, 3083 (2012)
6. Y. Gu, Green Chem. 14, 2091 (2012)
7. B.H. Rotstein, S. Zaretsky, V. Rai, A.K. Yudin, Chem. Rev. 114, 8323 (2014)
8. G. Ge, W. Ping, L. Peng, Z. Weihong, M. Liping, Z. Zhanhui, Chin. J. Org. Chem. 38, 846 (2018)
9. M. Zhang, Q.Y. Fu, G. Gao, H.Y. He, Y. Zhang, Y.S. Wu, Z.H. Zhang, ACS Sustain. Chem. Eng. 5,
6175 (2017)
10. P.M. O’Byrne, R. Williams, J.J. Walsh, J.F. Gilmer, Pharmaceuticals 7, 595 (2014)
11. W. Yuan, B.N. Williams, Psychopharmacol. Bull. 44, 85 (2011)
12. L.G. Taylor, S.T. Bird, L. Sahin, M.S. Tassinari, P. Greene, M.E. Reichman, Pharmacoepidemiol.
Drug Saf. 26, 592 (2017)
13. M.R. Rezka, K.A. Badr, J. Pharm. Biomed. Anal. 98, 1 (2014)
14. R. Glaser, P. Hug, M. Drouin, A. Michel, J. Chem. Soc. Perkin Trans. 2, 1071 (1992)
15. G. Rabbani, M.H. Baig, E.J. Lee, W.K. Cho, J.Y. Ma, I. Choi, Mol. Pharm. 14, 1656 (2017)
16. C. Zhou, G. Wu, Y. Feng, Q. Li, H. Su, D. Mais, E.Y. Zhu, N. Li, Y. Deng, D. Yang, M.W. Wang,
Br. J. Pharmacol. 154, 440 (2008)
17. G. Zhao, T. Jiang, H. Gao, B. Han, J. Huang, D. Sun, Green Chem. 6, 75 (2004)
18. N. Azizi, L. Torkiyan, M.R. Saidi, Org. Lett. 8, 2079 (2006)
19. K. Li, T. He, C. Li, X.W. Feng, N. Wang, X.Q. Yu, Green Chem. 11, 777 (2009)
20. R. Qiu, S. Yin, X. Zhang, J. Xia, X. Xu, S. Luo, Chem. Commun. 31, 4759 (2009)
21. E. Rafee, S. Eavani, Green Chem. 13, 2116 (2011)
22. D. Zareyee, H. Alizadeh, RSC Adv. 4, 37941 (2014)
23. X. Chen, H. Sun, Y. Luo, Y. Jian, Y. Wu, W. Zhang, Z. Gao, RSC Adv. 6, 39343 (2016)
24. M.P. Pachamuthu, K. Shanthi, R. Luque, A. Ramanathan, Green Chem. 15, 2158 (2013)
25. Y. Wu, C. Chen, G. Jia, X. Zhu, H. Sun, G. Zhang, W. Zhang, Z. Gao, Chem. Eur. J. 20, 1 (2014)
26. H.B. Wang, N. Yao, L. Wang, Y.L. Hu, New J. Chem. 41, 10528 (2017)
27. W. Senapak, R. Saeeng, U. Sirion, RSC Adv. 7, 30380 (2017)
28. A.T. Khan, T. Parvin, L.H. Choudhury, Eur. J. Org. Chem. 5, 834 (2008)
29. H.M. Yang, L. Li, F. Li, K.Z. Jiang, J.Y. Shang, G.Q. Lai, L.W. Xu, Org. Lett. 13, 6508 (2011)
30. K. Bahramia, M.M. Khodaeia, M. Mohammadia, N. Babajania, J. Chem. Res. 38, 223 (2014)
31. M. Tajbakhsh, M. Farhang, A.A. Hosseini, J. Iran. Chem. Soc. 11, 665 (2014)
32. H. Ghafuri, B. Ghorbani, A. Rashidizadeh, M. Talebi, M. Roshani, Appl. Organomet. Chem. 32, 41
(2018)
33. G.O.A. Haline, A.B. Giovana, M.R. Luciana, L. Aline, C.B. Heibbe, N.E. Marcos, J.L. Macedo,
W.A. Silva, B.A.D. Neto, Tetrahedron 70, 3306 (2014)
34. M. Rueping, E. Sugiono, F.R. Schoepke, Synlett 9, 1441 (2007)
35. B. Movassagh, L. Tahershamsi, A. Mobaraki, Tetrahedron Lett. 56, 1851 (2015)
36. M. Wang, Z. Song, Y. Liang, Prep. Biochem. Biotechnol. 41, 1 (2011)
37. J.P. Hallett, T. Welton, Chem. Rev. 111, 3508 (2011)
38. A.S. Amarasekara, Chem. Rev. 116, 6133 (2016)
39. B. Maiti, K. Chanda, C.M. Sun, Org. Lett. 11, 4826 (2009)
40. K. Chanda, B. Maiti, C.C. Tseng, C.M. Sun, ACS Comb. Sci. 14, 115 (2012)
41. W. Miao, T.H. Chan, Adv. Synth. Catal. 348, 1711 (2006)
42. S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J.P. Cheng, Angew. Chem. Int. Ed. 45, 3093 (2006)
1 3

Ionic liquid‑immobilized proline(s)…
43. D.E. Siyutkin, A.S. Kucherenko, M.I. Struchkova, S.G. Zlotin, Tetrahedron Lett. 49, 1212 (2008)
44. M. Lombardo, M. Chiarucci, A. Quintavalla, C. Trombini, Adv. Synth. Catal. 351, 2801 (2009)
45. Z. Zheng, B. Perkins, B. Ni, J. Am. Chem. Soc. 132, 50 (2010)
46. S.V. Kochetkov, A.S. Kucherenko, S.G. Zlotin, Eur. J. Org. Chem. 2011, 6128 (2011)
47. Y. Qiao, J. He, B. Ni, A.D. Headley, Adv. Synth. Catal. 354, 2849 (2012)
48. Y. Qiao, A.D. Headley, Catalysts 3, 709 (2013)
49. V.G. Lisnyak, A.S. Kucherenko, E.F. Valeev, S.G. Zlotin, J. Org. Chem. 80, 9570 (2015)
50. B. Maiti, K. Chanda, M. Selvaraju, C.C. Tseng, C.M. Sun, A.C.S. Comb, Science 15, 291 (2013)
51. S. Roshandel, S.C. Suri, J.C. Marcischak, G.K.S. Prakash, Green Chem. 20, 3700 (2018)
52. V.G. Khiratkar, K.R. Balinge, K.J. Bhansali, P.R. Bhagat, Res. Chem. Intermed. 44, 787 (2018)
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional afliations.
Afliations
M. D. Prabhakara1 · Barnali Maiti1
* Barnali Maiti
barnalimaiti.m@gmail.com
1
Department of Chemistry, School of Advanced Science, Vellore Institute of Technology,
Vellore 632014, India
1 3