Novel Bronsted acidic ionic liquid ([CMIM][CF3COO]) prompted multicomponent hantzsch reaction for the eco-friendly synthesis of acridinediones: An efficient and recyclable catalyst

Article abstract of DOI:10.1007/s10562-014-1202-z

A novel, highly efficient and recyclable Bronsted acidic ionic liquid ([CMIM][CF3COO]) has been successfully implemented for the synthesis of acridinediones in aqueous media. Recyclability of novel catalyst, high yields, use of environmentally benign aque

Full text of DOI:10.1007/s10562-014-1202-z

Catal Lett
DOI 10.1007/s10562-014-1202-z
Novel Brønsted Acidic Ionic Liquid ([CMIM][CF3COO])
Prompted Multicomponent Hantzsch Reaction
for the Eco-Friendly Synthesis of Acridinediones:
An Efficient and Recyclable Catalyst
•
Dayanand Patil Dattatray Chandam
•
•
Abhijeet Mulik Prasad Patil Surybala Jagadale
•
•
•
Rajni Kant Vivek Gupta Madhukar Deshmukh
•
Received: 10 November 2013 / Accepted: 19 January 2014
ꢀ Springer Science+Business Media New York 2014
Abstracts A novel, highly efficient and recyclable
Brønsted acidic ionic liquid ([CMIM][CF3COO]) has been
successfully implemented for the synthesis of acridinedi-
ones in aqueous media. Recyclability of novel catalyst,
high yields, use of environmentally benign aqueous media
as solvent, simple product isolation, high atom economy
and sidestep to column chromatography are the noteworthy
features of this protocol. This protocol is competent for
producing wide library of acridinediones in good to
excellent yields. Furthermore, molecular structure and
relative stereochemistry of 4c and 4s derivatives were
confirmed by single-crystal X-ray diffraction.
natural products, drug like molecules [1–3]. MCRs tactics
are proclaimed to be economic, cost- and time-effective
attributing its properties such as reduction in steps thereby
saving synthetic time, efficient inexpensive purification
process, synthetic convergence as well as selectivity and
synthetic efficiency over traditional chemical reactions
thereby attracted contemporary organic chemistry [4, 5].
Acridine 1,8-diones are an important class of heterocy-
cles containing a 1;4-DHP parent nucleus, are induced with
high efficiencies with several applications such as photo-
initiators, laser activity, fluorescence [6–9], laser dyes [10–
12], electrochemical and photo-physical properties [13].
The 1,4-DHP derivatives contribute as a very significant
compound due of their abundant pharmacological proper-
ties [14]. In particulars dihydropyridine drugs such as
nifedipine, nicardipine, amlodipine and other are effective
cardiovascular agents for the treatment of hypertension
[15–17] (Fig. 1). 1,4-DHP have also been known for their
calcium channel activity, moreover this heterocyclic ring
constitutes variety of bioactive compounds such as vaso-
dilator, bronchodilator, antiatheroscntific, antidiabetic,
antitumor, and anti-inflammatory agents [18]. Further
studies have discovered that these compounds exhibit
diverse medical function such as neuroprotectus, platelet
antiaggregaters and chemosensitizers [19].
Keywords Acridinediones Á Brønsted ionic liquid Á
Enamine Á Multicomponent reaction
1 Introduction
MCR’s endowed with notable properties as simpler methods
and operations as compared to the conventional multistep
methods of heterocycles synthesis have gained enormous
interest in diversity oriented synthesis of skeletons found in
D. Patil Á D. Chandam Á A. Mulik Á S. Jagadale Á
M. Deshmukh (&)
Heterocyclic Research Laboratory, Department of Chemistry,
Shivaji University, Kolhapur, MS 416 004, India
e-mail: shubhlaxmi111@gmail.com
The general synthesis of 1,4-DHP by Hantzsch method
involves one pot cyclocondensation of aldehydes with
dicarbonyls and ammonium acetate refluxing in ethanol [20].
There are several methods reported for the synthesis of 1,4-
dihydropyridines from dimedone, aldehyde through differ-
ent nitrogen sources like urea [21], methyl amine [22], dif-
ferent aniline or ammonium acetate [23] via traditional
heating in organic solvent and in presence of triethyl benzyl
ammonium chloride (TEBAC) [24], p-dodecyl benzene
sulphonic acid (DBSA) [25], L-proline [26], amberlyst-15
P. Patil
Department of Agrochemicals and Pest Management, Shivaji
University, Kolhapur, MS 416 004, India
R. Kant Á V. Gupta
X-ray Crystallography Laboratory, Department of Physics &
Electronics, University of Jammu, Jammu Tawi 180 006, India
123

D. Patil et al.
Fig. 1 Representative antihypertensive compounds
[27], under microwave [28], TMSCl-NaI [29], metal triflates
[30], I2 [31],CeCl3Á7H2O [32], SiO2-Pr-SO3H [33], CAN
[34], Fe3O4 Nanoparticles [35] and MCM-41-SO3H [36].
However, most of the methods are blemished by aspects
such as unsatisfactory yield, prolonged duration, inconve-
nient availability of reagent, toxic solvents and expensive
catalysts, Hence the development of an efficient synthesis
of Hantzsch 1,4-dihydropyridines seemed to be of prime
importance. Recently avail of ionic liquids as catalyst or
solvents in multicomponent reactions has been gaining
elevated interest in green synthesis [37–39]. Initially ionic
liquids have been introduced as alternative green reaction
media attributed to their unique physico-chemical proper-
ties, such as negligible vapor pressure, non-volatility, non-
inflammability, thermal and chemical stability and con-
trolled miscibility in organic solvents which proves their
importance in controlling reactions as catalysts [40–42].
Amongst them, Brønsted acidic ionic liquids displayed
potential catalytic characteristics over conventional homo-
geneous/heterogeneous acidic catalysts in chemical proce-
dures as they are flexible, recyclable and reusable, non-
corrosive and possess ability to be used as dual solvents and
catalysts [43–46]. In continuation of our investigation on the
development of eco-friendly methodologies and applications
of ionic liquids as catalysts in multicomponent reactions [47],
herein, we demonstrate an expedient and highly efficient
protocol for one pot multicomponent synthesis of acridined-
iones derivatives from various aryl aldehydes, dimedone and
ammonium acetate using novel Brønsted acidic ionic liquid
[CMIM][CF3COO] as an effective, recyclable and reusable
catalyst (Scheme 1). To the best of our knowledge, our cata-
lyst [CMIM][CF3COO] is novel and used for first time.
purification. All the melting point check on Labstar melting
apparatus was uncorrected. The IR spectra was run on a
Perkin-Elmer, FTIR-1600 spectrophotometer and expres-
sed in cm-1 (KBr). 1H and 13C NMR spectra were recorded
on Bruker Avance (300 MHz) spectrometer in CDCl3, D2O
or DMSO-d6 using TMS as the internal standard. The LC-
MS spectrums were recorded by Shimadzu LC-MS-2010
equipped with electron spray ionization interface.
2.2 X-Ray Structure Analysis
X-ray diffraction data of compounds 4c and 4s were col-
lected at T = 298 and 293 K on a Bruker APEXII CCD
and CrysAlis PRO Oxford diffractometer with graphite
˚
monochromated Mo Ka (k = 0.71073 A) radiation.
Table 4 shows the unit cell parameters and other crystal-
lographic details. The determination of cell refinement and
data reduction were performed with program SAINT and
CrysAlis PRO [51]. The structure was solved using the
direct methods of program SHELXS97 and refined aniso-
tropically by full-matix least-square on F2 was carried out
with the program SHELXL97 [52].
2.3 Synthesis of Ionic Liquid
TheBrønstedacidicionicliquidsuchas3-(carboxymethyl)-1-
methyl-1H-imidazol-3-ium trifluoroacetate [CMIM][CF3-
COO] was synthesized as shown in Scheme 2.
2.3.1 Preparation of [CMIM][CF3COO]
A mixture of 1-methyl imidazole (10 mmol), chloroacetic
acid (10 mmol) and dry acetone (40 ml) were charged into
250 ml round bottom flask at RT. The reaction was per-
formed 5–7 h under reflux condition. After completion of
reaction (checked by TLC), the reaction mixture was cooled
and then a stoichiometric amount of trifluoroacetic acid
(99 %) was slowly added at 5–10 ꢁC under stirring over
30 min. Then the reaction was stirred an additional period of
1 h at RT. The white solid was observed, filter and washed
2 Experimental
2.1 General
The chemicals were purchased from Thomas Baker,
Sigma-Aldrich and used as received without further
123

Novel Brønsted Acidic Ionic Liquid ([CMIM][CF3COO])
Scheme 1 Synthesis of 1,8-
dioxoacridinediones
Scheme 2 Synthesis of ionic
liquid [CMIM][CF3COO]
3–4 times with acetone (10 ml) to remove non-ionic residue.
Finally, it was dried under vacuum at 50 ꢁC for 2 h to give
[CMIM][CF3COO] as a white solid in 97 % yield and further
it used as a catalyst after checking pH (pH 1.7).
[Compound 8: 3-(Carboxymethyl)-1-methyl-1H-imida-
zol-3-ium trifluoroacetate]
ESI–MS (?ve ion) (m/z): 141(M?); ESI–MS (-ve ion)
(m/z): 112.9(M?);
1
After 4th run H NMR (300 MHz, D2O): d 8.88 (s, 1H,
Ar–H), 7.49-7.62 (m, 2H, Ar–H), 5.08 (s, 2H, CH2), 3.84
(s, 3H, CH3);
Anal. Calcd.for C8H9F3N2O4 (254.162): C, 37.80; H,
3.57; N, 11.02. Found: C, 37.73; H, 3.63; N, 11.09.
2.4 General Procedure for the Synthesis
of Acridinediones (4a–4z)
2.5.2 3,3,6,6-Tetramethyl-9-(4-chlorophenyl)-3,4,6,7,9,10-
hexahydroacridine-1,8-dione (4c)
In a 50 ml round bottom flask, a mixture of dimedone 1
(2 mmol), aldehyde 2 (1 mmol), ammonium acetate 3
(1.5 mmol) and [CMIM][CF3COO] (30 mol%) in aqueous
ethanol (1:1, 7 ml) was stirred at 80 ꢁC for 1–1.5 h. The
progress of reaction was monitored by TLC. After com-
pletion of reaction, the mixture was gradually cool to RT
and poured on ice water under stirring, solid was precipi-
tate out. Then, filter the product and recrystallized in eth-
anol. The catalyst [CMIM][CF3COO], being aqueous
ethanol soluble, was recovered from the filtrate.
Yellow solid; mp [300 ꢁC; IR (KBr): 3432, 3279, 3174,
3057, 2955, 1649, 1609, 1489, 1398, 1366 cm-1 1H
;
NMR(300 MHz, DMSO-d6):
d 8.18 (s, 1H, NH),
7.28–7.26(d, 2H, J = 5.7 Hz, Ar–H),7.17–7.14 (d, 2H,
J = 8 Hz, Ar–H), 5.04 (s, 1H, CH), 2.29–2.11 (m, 8H,
CH2), 1.08 (s, 6H, CH3), 0.96 (s, 6H, CH3); 13C NMR
(75 MHz, DMSO-d6): d 195.9, 153.8, 149.9, 145.1, 131.6,
129.4, 128.0, 112.5, 50.8, 40.6, 40.4, 33.2, 32.5, 29.6, 27.0;
ESI–MS (m/z): 384.3 (M?H)?;
Anal. Calcd. for C23H26ClNO2 (383.911): C, 71.96; H,
6.83; N, 3.65. Found: C, 71.87; H, 6.75; N, 3.73.
2.5 Spectral Data for ILs and Some Representative
Acridinediones Derivatives
2.5.3 3,3,6,6-Tetramethyl-9-(4-hydroxy,3-methoxyphenyl)-
2.5.1 3-(Carboxymethyl)-1-methyl-1H-imidazol-3-ium
3,4,6,7,9,10-hexahydroacridine-1,8-dione (4m)
trifluoroacetate [CMIM][CF3COO] (8)
Yellow solid; mp 295–298 ꢁC; IR (KBr): 3409, 3274,
White solid; mp 190–195 ꢁC;
3168, 3049, 1623, 1511, 1370 cm-1
;
Fresh 1H NMR (300 MHz, DMSO-d6): d 13.67 (brs, 1H,
OH), 9.20 (s, 1H, Ar–H), 7.74-7.76(m, 2H, Ar–H), 5.18 (s,
2H, CH2), 3.91 (s, 3H, CH3);
1H NMR (300 MHz, DMSO-d6): d 9.69(s, 1H, OH),
8,71 (brs, 1H, NH), 7.69 (s, 1H, Ar–H), 7.44
(s, 2H, Ar–H), 5.69(s, 1H, CH), 4.61 (s, 3H, OCH3),
3.25–2.88 (m, 8H, CH2), 1.89 (s, 6H, CH3), 1,77 (s, 6H,
CH3); 13C NMR (75 MHz, DMSO-d6): d 195.4, 149.0,
138.9, 114.6, 112.8, 55.7, 50.8, 32.6, 32.4, 29.6, 26.9;
Anal. Calcd. for C24H29NO4 (395.491): C, 72.89; H,
7.39; N, 3.54. Found: C, 72.81; H, 7.33; N, 3.63.
1H NMR (300 MHz, D2O): d 9.0 (s, 1H, Ar–H),
7.64–7.65 (d, 2H, Ar–H), 5.12 (s, 2H, CH2), 3.89 (s, 3H,
CH3); 13C NMR (75 MHz, DMSO-d6): d 168.2, 159.5,
159.0, 158.5, 158.0, 137.9, 123.9, 123.2, 120.9, 117.1,
113.3, 109.5, 49.9, 35.9;
123

D. Patil et al.
1H NMR (300 MHz, CDCl3): d 11.89 (s, 1H, NH), 8.42-
8.37 (m, 2H, Ar–H), 7.39–7.37 (d, 1H, J = 8.1 Hz, Ar–H),
7.26–7.18 (m, 1H, Ar–H), 5.53 (s.1H, CH), 2.50–2.19 (m,
8H, CH2), 1.23 (s, 6H, CH3), 1.11 (s, 6H, CH3); 13C NMR
(75 MHz, CDCl3): d 190.8, 189.4, 148.6, 147.0, 134.4,
133.7, 122.9, 114.6, 46.9, 31.3, 31.0, 29.6, 27.3; ESI–MS
(m/z): 351.15 (M?H)?;
2.5.4 3,3,6,6-Tetramethyl-9-(3,4-dimethoxyphenyl)-
3,4,6,7,9,10-hexahydroacridine-1,8-dione (4n)
Yellow solid; mp 286–290 ꢁC; IR (KBr): 3273, 3200,
3071, 2954, 1642, 1610 cm-1
;
1H NMR(300 MHz, CDCl3): d 7.69 (s, 1H, NH), 6.92-
6.91 (d, 1H, J = 1.8 Hz, Ar–H), 6.84–6.81 (m, 1H, Ar–H),
6.68–6.65 (d, 1H, J = 8.4 Hz, Ar–H), 5.04 (s, 1H, CH),
3.80 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 2.31–2.12 (m, 8H,
CH2), 1.05 (s, 6H, CH3), 0.96 (s, 6H, CH3);
Anal. Calcd. for C22H26N2O2 (350.454): C, 75.40; H,
7.48; N, 7.99. Found: C, 75.31; H, 7.44; N, 8.05.
13C NMR (75 MHz, CDCl3): d 195.8, 148.7, 148.4,
147.1, 139.4, 119.8, 113.2, 111.8, 110, 55.7, 55.6, 50.8,
40.7, 32.9, 32.5, 29.5, 26.9; ESI–MS (m/z): 432.15
(M?Na)?;
2.5.8 3,3,6,6-Tetramethyl-9-(2-hydroxyphenyl)-
3,4,6,7,9,10-hexahydroacridine-1,8-dione (4s)
Yellow solid; mp [300 ꢁC; IR (KBr): 3405, 3265, 3083,
2943, 1649 cm-1
;
Anal. Calcd. for C25H31NO4 (409.571): C, 73.32; H,
7.63; N, 3.42. Found: C, 73.41; H, 7.72; N, 3.47.
1H NMR(300 MHz, DMSO-d6): d 9.64 (brs, 1H, OH),
9.48 (s, 1H, NH), 6.96–6.89 (m, 2H, Ar–H), 6.70–6.66 (m,
2H, Ar–H), 4.85 (s, 1H, CH), 2.52-2.03 (m, 8H, CH2), 1.02
(s, 6H, CH3), 0.90 (s, 6H, CH3); 13C NMR (75 MHz,
DMSO-d6): d 196.4, 153.6, 151.6, 134.4, 128.6, 127.4,
120.1, 117.7, 111.7, 50.3, 32.5, 29.3, 27.0, 26.9; ESI–MS
(m/z): 366.3 (M?H)?;
2.5.5 3,3,6,6-Tetramethyl-9-(3-trifluoromethylphenyl)-
3,4,6,7,9,10-hexahydroacridine-1,8-dione (4o)
Yellow solid; mp [300 ꢁC; IR (KBr): 3270, 3186, 3068,
2963, 1644, 1616 cm-1
;
1H NMR(300 MHz, DMSO-d6): d 8.92 (brs,1H,NH),
7.51–7.40 (m, 2H, Ar–H), 7.21–7.20 (d, 2H, J = 4.8 Hz,
Ar–H), 4.92(s, 1H, CH), 2.49–1.95 (m, 8H, CH2), 0.98 (s,
6H, CH3), 0.82 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-
d6): d 195.2, 149.6, 148.1, 131.8, 128.1, 112.0, 50.6, 40.4,
40.3, 40.2, 39.9, 39.6, 39.3, 33.7, 32.4, 29.5, 26.7; ESI–MS
(m/z): 418 (M?);
Anal. Calcd. for C23H27NO3 (365.465): C, 75.59; H,
7.45; N, 3.83. Found: C, 75.54; H, 7.42; N, 3.87.
Table 1 Optimization solvent and reaction conditions for the syn-
thesis of acridinediones
Entry Solvent
Temp. (ꢁC) Time (min) Yield
(%)a
Anal. Calcd. for C24H26F3NO2 (417.463): C, 69.05; H,
6.28; N, 3.36. Found: C, 68.95; H, 6.19; N, 3.34.
b
1
Water
RT
RT
RT
80
360
240
240
300
150
180
130
85
–
–
–
–
b
b
b
2
Ethanol
Methanol
Water
2.5.6 3,3,6,6-Tetramethyl-9-(3-fluorophenyl)-3,4,6,7,9,10-
3
hexahydroacridine-1,8-dione (4p)
4
5
Ethanol
Methanol
78
75
Yellow solid; mp [300 ꢁC; IR (KBr): 3217, 3070, 2954,
6
64
67
1627 cm-1
;
7
Water?ethanol (2:1) 80
Water?ethanol (1:1) 80
63
1H NMR (300 MHz, DMSO-d6): d 9.19 (brs, 1H, NH),
7.64–7.48 (m, 3H, Ar–H), 7.26–7.24 (d, 1H, J = 6.6 Hz,
Ar–H), 5.53 (s, 1H, CH), 2.91–2.59 (m, 8H, CH2), 1.57 (s,
6H, CH3), 1.44 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-
d6): d 190.5, 159.3, 144.7, 144.6, 144.4, 124.2, 124.1,
118.9, 110.0, 109.0, 107.0, 45.0, 53.0, 34.0, 28.0, 27.0,
23.0, 22.0; ESI–MS (m/z): 368 (M?H)?;
8
86
9
Acetone
60
80
80
80
180
120
110
135
300
240
120
180
20
10
11
12
13
14
15
16
Isopropyl alcohol
Glycerol
70
75
Acetonitrile
45
Dimethyl formamide 80
25
Dimethyl sulfoxide
[CMIM][CF3COO]
–
80
80
80
37
Anal. Calcd. for C23H26FNO2 (367.456): C, 75.18; H,
7.13; N, 3.81. Found: C, 75.25; H, 7.19; N, 3.87.
Trace
b
–
2.5.7 3,3,6,6-Tetramethyl-9-(3-pyridine)-3,4,6,7,9,10-
Reaction condition: dimedone (2 mmol), 4-OH benzaldehyde
(1 mmol), ammonium acetate (1.5 mmol), [CMIM][CF3COO]
(30 mol%)
hexahydroacridine-1,8-dione (4r)
a
Isolated yield
Light yellow solid; mp 298–300 ꢁC; IR (KBr): 3432, 3270,
b
3172, 2957, 1634 cm-1
;
No reaction
123

Novel Brønsted Acidic Ionic Liquid ([CMIM][CF3COO])
using novel ionic liquid [CMIM][CF3COO] as a green and
recyclable catalyst in aqueous ethanol (1:1) at 80 ꢁC
(Scheme 1).
Table 2 Screening of catalyst concentration
Entry
Catalyst (mol%)
Time (min)
Yield (%)a
b
1
2
3
4
5
6
–
350
300
170
110
85
–
Initially, the ionic liquid 3-(carboxymethyl)-1-methyl-
5
Trace
35
1H-imidazol-3-ium trifluoroacetate was synthesized
1
(Scheme 2) and identified by H NMR, 13C NMR, mass
10
20
30
40
63
and elemental analyses. After characterization of ionic
liquid, to evaluate the efficiency and applicability of our
new catalyst to synthesis of acridinediones, we choose
dimedone (2 mmol), 4-OH benzaldehyde (1 mmol),
86
85
85
Reaction condition: dimedone (2 mmol), 4-OH benzaldehyde
(1 mmol), ammonium acetate (1.5 mmol) in 7 ml aqueous ethanol
(1:1) at 80 ꢁC
ammonium acetate (1.5 mmol) as
a substrates and
30 mol% of [CMIM][CF3COO] as catalyst proportion for
model reaction. Successively, we focused our initial
investigation on the effect of various solvents and their
mixtures on model reaction at different temperatures
(Table 1). It was observed that, the reaction doesn’t mar-
ches successfully in sole solvents like water, EtOH and
MeOH even after prolonged stirring at room temperature
(Table 1, entries 2, 3). However, best result was observed
using same proportional mixture (1:1) of water/ethanol at
a
Isolated yield
b
No reaction
3 Results and Discussion
At this instance, we outlined an eco-friendly protocol for
the multicomponent synthesis of acridinediones scaffolds
Yielda
(%)
MP ꢁC
(observed)
MP ꢁC
(literature)[Ref.]
Table 3 [CMIM][CF3COO]
catalyzed synthesis of
acridinediones derivatives
Entry
Ar
Product
Time
(min)
1
4-NO2 C6H4
C6H5
4a
4b
4c
4d
4e
4f
70
80
65
85
90
67
72
90
87
85
80
78
85
85
70
70
65
60
87
85
78
73
80
75
81
180
90
87
89
86
84
88
87
84
83
85
83
84
83
85
87
89
90
81
82
83
87
86
88
83
84
[300
261–262 [24]
251–252 [24]
[300 [24]
284–286 [29]
227–228 [29]
285–286 [29]
281–282 [29]
266–267 [29]
324–326 [29]
324–326 [29]
294–296 [29]
221–223 [28]
295–298 [48]
286–290 [49]
–
2
285–289
[300
3
4-Cl C6H4
4
4-OH C6H4
271–274
270–275
[300
5
4-CH3 C6H4
3-NO2 C6H4
3-Cl C6H4
6
7
4g
4h
4i
283–285
275–277
[300
8
4-OCH3 C6H4
2;3-(OCH3)2C6H3
3-OH,4-OCH3 C6H3
2-OCH3 C6H4
2-Cl C6H4
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
4j
[300
4k
4l
[300
263–264
294–296
288–291
[300
4-OH, 3-OCH3 C6H3
3,4-(OCH3)2 C6H3
3-F3C C6H4
3-F C6H4
4m
4n
4o
4p
4q
4r
4s
[300
300 [50]
4-F C6H4
[300
275–276 [24]
–
3-CHO C5H4N
2-OH C6H4
298-300
[300
–
4- (CH3)2N C6H4
4-Br C6H4
4t
269–271
[300
256–257 [24]
330–332 [32]
288–289 [24]
328–330 [32]
[302 [32]
293–295 [28]
–
Reaction condition: dimedone
(2 mmol), aldehyde (1 mmol),
ammonium acetate (1.5 mmol)
and [CMIM][CF3COO]
4u
4v
4w
4x
4y
4z
3-Br C6H4
294–297
[300
4-CN C6H4
(30 mol%) in 7 ml aqueous
ethanol (1:1) at 80 ꢁC
3-OH C6H4
[300
2-NO2 C6H4
n-butanal
284–287
–
a
Isolated yields
b
–
b
No reaction
123

D. Patil et al.
80 ꢁC, which afforded 86 % yield of targeted molecules
within 85 min (Table 1, entry 8).
Next, the same model reaction was carried out at 80 ꢁC
in excess of [CMIM][CF3COO], only trace amount of
product was formed, furthermore at solvent free condition
the reaction didn’t progressed even after prolonged stirring
(Table 1, entries 15,16).
The results revealed that the reaction temperatures and
choice of solvents significantly influence on the product
yield and time of reaction completion.
Consequently, to optimize the concentration of catalyst
for the synthesis of targeted molecule, we carried a reaction
of dimedone, 4-OH benzaldehyde and ammonium acetate
with different amount of [CMIM][CF3COO] in aqueous
ethanol (1:1) medium at 80 ꢁC (Table 2, entries 1–5). The
result signifies that with increase in the concentration of
catalyst from 0 to 30 mol%, the yield of product 4a
increased up to 86 %. However, further increasing the
concentration of catalyst from 30 to 40 mol%, there was no
considerable change in the yield of product observed
Fig. 2 X-ray crystal structure of 4c with atom-labeling scheme
Table 4 Crystal data and structure refinement for 4c and 4s
Identification code
4c
4s
Empirical formula
Formula weight
C23 H26ClNO2
383.90
C23 H27NO3
365.46
Temperature
298(2) K
293(2) K
˚
0.71073 A
˚
0.71073 A
Wavelength
Crystal system, space group
Unit cell dimensions
Orthorhombic, Pna2(1)
˚
Orthorhombic, Pna2(1)
0
˚
a = 14.1368(4) A a = 90 .
a = 13.669(5) A a = 90ꢁ
0
˚
˚
b = 14.1212(4) A b = 90 .
b = 14.753(5) A b = 90ꢁ
0
˚
˚
c = 10.7332(3) A c = 90 .
c = 10.043(5) A c = 90ꢁ
Volume
2142.65(10) A3
2025.3(14) A3
Z, calculated density
Absorption coefficient
F(000)
4, 1.190 mg/m3
0.195 mm-1
4, 1.199 mg/m3
0.079 mm-1
816
784
Crystal size
0.22 9 0.16 9 0.10 mm
0.3 9 0.2 9 0.1 mm
Theta range for data collection
Limiting indices
2.04ꢁ to 24.99ꢁ
3.61ꢁ to 26.00ꢁ
-16 B h B 16, -16 B k B 16, -11 B l B 12
24469/3,642 [R(int) = 0.0,208]
= 24.99 99.8 %
-16 B h B 16, -18 B k B 18, -12 B l B 12
28,953/3,959 [R(int) = 0.0402]
= 26.00 99.7 %
Reflections collected/unique
Completeness to theta
Absorption correction Multi-scan
Max. and min. transmission
Refinement method
0.9808 and 0.9584
1.00000 and 0.86047
Full-matrix least-squares on F2
3,642/1/248
Full-matrix least-squares on F2
3,959/1/253
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2sigma(I)]
R indices (all data)
1.033
1.332
R1 = 0.0314, wR2 = 0.0834
R1 = 0.0355, wR2 = 0.0877
0.01(7)
R1 = 0.1017, wR2 = 0.2985
R1 = 0.1226, wR2 = 0.3321
-1(3)
Absolute structure parameter
Largest diff. peak and hole
CCDC number
0.209 and -0.274 e.A-3
0.799 and -0.331 e.A-3
CCDC 965866
CCDC 965867
123

Novel Brønsted Acidic Ionic Liquid ([CMIM][CF3COO])
(Table 2, entry 6). Using these optimized conditions of
30 mol% of [CMIM][CF3COO] and aqueous ethanol (1:1)
to check the generality and versatility of the protocol we
reacted several substituted aryl aldehydes, dimedone and
ammonium acetate which afforded good to excellent yields
(Table 3, entries 1–25).
In general, we found that the reactions of aromatic alde-
hydes containing electron withdrawing group at different
positions (Table 3, entries 1,3,6,7,12,15–17,21–23,25)
prove to be predominant attributed to high yield of products
than the reactions of aldehydes containing electron donating
group (Table 3, entries 4,5,8–11,13,14,19,20,24). Along
with this our protocol has also been found to be in good
agreement with heteroaromatic aldehyde affording resultant
product in good yield (Table 3, entry 18). Further, we
examined aliphatic aldehyde such as n-butanal instead of
aromatic or heteroaromatic aldehydes, however there was no
product formed after prolonged stirring (Table 3, entry 26).
All the products were crystalline and fully characterized on
Fig. 3 X-ray crystal structure of 4s with atom-labeling scheme
1
the basis of their melting points and spectral data (IR, H-
NMR, 13C-NMR and LC–MS) with those of authentic sample
[24, 28, 29, 32, 48–50]. The molecular structure of compound
3,3,6,6-tetramethyl-9-(4-chlorophenyl)-3,4,6,7,9,10-hexahy-
droacridine-1,8-dione 4c and 3,3,6,6-tetramethyl-9-(2-
hydroxyphenyl)-3,4,6,7,9,10-hexahydroacridine-1,8-dione
4s were also confirmed by single crystal X- ray analysis
(Table 4; Figs. 2, 3).
Table 5 Geometry of intra- and inter molecular hydrogen bonds for
4c and 4s
Compound D–H…A
D–H
˚
(A)
H…A
(A)
D…A
(A)
[D–H…A
(o)]
˚
˚
4c
4s
N1–H1…O1 0.86
1.86
2.718
2.661
178.00
167.60
O20–
H20…O1
C9–
H9…O20
N1–
H12…O8i
0.728
0.98
0.86
1.946
2.502
2.195
2.898
2.809
103.95
128.23
In X-ray single crystal analysis the geometry of 4c and
4s are orthorhombic. The central rings of acridinediones in
4c and 4s are in boat conformation whiles other two
cyclohexanone rings of dimedone in half chair conforma-
tions. The geometry of inter and intra-molecular hydrogen
Symmetry code: (i) x - 1/2, -y ? 1/2, ?z
Scheme 3 Pausible mechanism for the formation of 1,8-dioxoacridinediones
123

D. Patil et al.
bonds for 4c and 4s as shown in Table 5, Moreover the
intermolecular packing arrangement of molecules along b
axis for 4s as shown in Fig. 4.
(96 %) and reused in the subsequent reaction for four
consecutive times, giving an average of 84 % yield of
isolated product (Fig. 5). From these results, it was
noticed that the [CMIM][CF3COO]proved as highly
efficient and recyclable catalyst with negligible loss in its
catalytic activity. The recovered catalyst after four
A plausible mechanism for the formation of acridined-
iones 4 is outlined in Scheme 3. The reaction is initiated by
the Knoevenagel condensation of aryl aldehyde 1 with a
molecule of dimedone 2 to form Knoevenagel product 5,
and simultaneously condensation of another molecule of
dimedone 2 with ammonium acetate 3 to provide enamine
6. Finally, the subsequent Michael addition between 6 and
5 followed by intramolecular cyclization and dehydration
affords the product 4.
The reusability and recyclability are the key aspects in
viewpoint point of green chemistry, thus checked it for
our novel catalyst [CMIM][CF3COO]. The recyclability
of the catalyst was checked on the model reaction using
30 mol% of [CMIM][CF3COO] in aqueous ethanol
media. After each run, the filtrate was collected of fil-
tered product and the containing ionic liquid was
extracted with diethyl ether (2 9 15 ml) to remove
organic impurities. Then the water was evaporated and
catalyst was further dried at 50 ꢁC under reduced pres-
sure. The catalyst was recovered in excellent yields
Fig. 5 Reusable and recyclability of catalyst for synthesis of 4d
Fig. 4 The packing
arrangement of molecules
viewed along the b axis. The
dashed lines show
intermolecular N–H…O
hydrogen bonds. Only H atoms
involved in hydrogen bonds are
shown
123

Novel Brønsted Acidic Ionic Liquid ([CMIM][CF3COO])
Table 6 Comparison of the
results of [CMIM][CF3COO]
with literature reported catalysts
Entry Catalyst
Conditions
H2O/reflux
Reaction time (h/min) Yield (%) Reference
1.
2.
3.
4.
5.
6.
7.
L-proline
130–200 min
78–92
88–95
85–95
94–98
75–90
61–98
81–90
[26]
H2O/100 ꢁC/microwave 3–5 min
[Bmim][BF4]/55 ꢁC
PEG 400/50 ꢁC
Solvent free/120 ꢁC
Solvent free/110 ꢁC
[28]
–
CeCl3.7H2O
3 h
[32]
CAN
3.5–4 h
[34]
Nano-Fe3O4
MCM-41-SO3H
10–50 min
10–110 min
[35]
[36]
[CMIM][CF3COO] H2O:EtOH (1:1)/80 ꢁC 60–90 min
[This work]
Physics & Electronics, University of Jammu, for providing single crystal
analysis data of compound 4c and 4s (CCDC 965866, 965867).
consecutive runs had no observable change in the
1
structure referring to the H-NMR spectrum in compar-
1
ison with fresh catalyst H NMR (8). These results imply
that the catalyst was highly stable and appropriately
capable for its reuse under these reaction’s conditions.
The applicability of the protocol for the synthesis of
acridinediones has been compared with some of the
previously reported catalysts in Table 6. The results have
been compared with respect to the reaction times and
yields. As demonstrated in Table 6, [CMIM][CF3COO]
is an uniformly or more proficient catalyst for this
multicomponent reaction in terms of yield and reaction
time.
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