Recyclable task-specific acidic ionic liquid [NMP]H2PO4: Microwave-assisted, efficient one-pot, two-step tandem synthesis of fused thiazolo[2,3-b]quinazolinone and thiazolo[2,3-b]quinazoline derivatives

Article abstract of DOI:10.1007/s11164-015-2249-1

A novel, time-effective, eco-conscious and microwave-assisted tandem one-pot, two-step reaction has been described for the synthesis of thiazolo[2,3-b]quinazolinone (4a-f) and thiazolo[2,3-b]quinazoline (5a-t) derivatives in quantitative yield in the pres

Full text of DOI:10.1007/s11164-015-2249-1

Res Chem Intermed
DOI 10.1007/s11164-015-2249-1
Recyclable task-specific acidic ionic liquid
[NMP]H2PO4: Microwave-assisted, efficient one-pot,
two-step tandem synthesis of fused thiazolo[2,3-
b]quinazolinone and thiazolo[2,3-b]quinazoline
derivatives
Gondru Ramesh1 Rajitha Gali1 Ravibabu Velpula1
Bavantula Rajitha1
•
•
•
Received: 12 July 2015 / Accepted: 28 August 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract A novel, time-effective, eco-conscious and microwave-assisted tandem
one-pot, two-step reaction has been described for the synthesis of thiazolo[2,3-
b]quinazolinone (4a–f) and thiazolo[2,3-b]quinazoline (5a–t) derivatives in quantita-
tive yield in the presence of inexpensive, acidic task-specific ionic liquid [NMP]
H2PO4. All the synthesized compounds were well established by comparison with their
literature values (1H NMR, melting points, mass spectrometry and elemental analysis).
The remarkable advantages of this methodology over existing conventional heating,
such as increasing yields, decreasing reaction times, formation of products in an
analytically pure form, operational simplicity, less energy consumption, cost-effec-
tiveness, recyclability and reusability of the catalyst, make this protocol ‘‘green’’ and
environmentally benign.
Electronic supplementary material The online version of this article (doi:10.1007/s11164-015-2249-1)
contains supplementary material, which is available to authorized users.
&
Bavantula Rajitha
rajitabhargavi@yahoo.com
1
Department of Chemistry, National Institute of Technology, Warangal,
Telangana State 506004, India
123

G. Ramesh et al.
Graphical Abstract
Keywords Green chemistry Á N-Methyl-2-pyrrolidonium dihydrogen phosphate Á
Microwave irradiation Á Multi-component reaction Á Solvent-free
Introduction
Nature has provided a beautiful atmosphere for all living beings to lead their life
healthier. But unfortunately, the most polluting species, mankind, has been
damaging the atmosphere by exploiting and polluting the environment by
consuming all the non-recyclable energy resources and dumping hazardous waste
materials. Hence, protecting and nurturing our mother atmosphere, thereby giving a
healthy environment and energy resources to our future generations, is an emerging
challenge to the scientific community by following the basic principles of green
chemistry [1–3].
In development of green approaches, during the past decades, many new
synthetic methodologies [e.g., the multi-component reaction (MCR) approach, solid
phase synthesis, ultrasonication, microwave irradiation, aqueous medium reactions,
solvent-free reactions, using ionic liquids (ILs) as duel solvent-catalysts and phase
transfer catalysis] and analytical techniques (grinding and micellar catalysis) have
been developed and employed in synthetic organic chemistry, focused towards
designing more environmentally sound and green procedures.
In this context, MCRs [4] have emerged as one of the most powerful
strategies that involves more than two easily accessible reactants to give multi-
functionalized complex structures in a single synthetic operation. This simple
atom economy and time-saving method became a major tool in the synthesis of
diverse combinatorial libraries [5] and complex organic molecules of potential
123

Recyclable task-specific acidic ionic liquid [NMP]H2PO4…
interest, particularly in the area of drug discovery [6, 7]. However, the multi-
component protocol is generally advantageous over stepwise and divergent
chemical processes in terms of lower reaction times, rapid reaction rates leading
to higher yields, and reproducibility [8].
Among the above-mentioned various synthetic methodologies, microwave-
assisted organic synthesis [9] has gained much attention as one of the important
alternatives to conventional heating for promoting a variety of organic transforma-
tions [10, 11] and also to compensate for drawbacks raised in classical synthesis.
Microwave irradiation has been preferred in the scientific community due to its
promising advantages, like a dramatic reduction in reaction times by choosing lower
energy pathways, selecting a suitable microwave energy and its uniform heat
distribution, simple purification steps by reducing the side products, lower energy
consumption and higher atom economy via optimized conditions.
From the view of green chemistry, the use of eco-friendly, non-flammable,
recyclable, task-specific dual solvent-catalyst ILs [12–14] has shown attractive
alternatives to traditional polluting homogeneous and heterogeneous catalysts and
volatile organic solvents. The synergistic combination of MCRs and task-specific
ILs (TSILs) has already proven to be an outstanding green protocol because of their
unique properties, including product distribution, negligible vapor pressure,
recyclability, catalyst-immobilization, thermal stability, tunable viscosity, miscibil-
ity with water and the ability to associate with reactants during activation with their
solvent cavities [15–18].
Due to their widespread biological application, fused thiazolo[2,3-b]quinazoli-
none and thiazolo[2,3-b]quinazolines have emerged as important lead molecules
in a variety of therapeutic areas. Their efficient synthesis has attracted the
attention of synthetic and medicinal chemists due to their broad range of
biological activities such as antibiofilm [19], antimicrobial [20], antioxidant [21],
anti-inflammatory [22], antitubercular [23], anticancer [24, 25] and antitumor
activities [26].
Scheme 1 Synthesis of thiazolo[2,3-b]quinazolinone (4a–f) and thiazolo[2,3-b]quinazoline derivatives
(5a–t). Reaction conditions: [NMP]H2PO4 (10 and 15 mol% for compound 4 and 5, respectively),
microwave (MW) irradiation (300 W), temperature (90 °C), 2–8 min, yield (92–98 %)
123

G. Ramesh et al.
In our previous work [27, 28], we described the synthesis of compounds 4 and 5
and evaluated them for their biological activity. However, the time and yields of
both of the title compounds were found to be good, but not satisfactory. Hence, in
order to overcome the time and yield limitations and in search of synergistic and
more sustainable synthetic protocols as of earlier work [29–31], we aimed to
develop a highly efficient and rapid green method. We report herein an eco-
compatible, highly efficient and simple protocol for the synthesis of thiazolo[2,3-
b]quinazoline (4a–f) and thiazolo[2,3-b]quinazolinone (5a–t) derivatives by com-
bined use of recyclable [NMP]H2PO4 as a dual green catalyst and microwave
irradiation via an MCR approach under solvent-free conditions (Scheme 1).
Experimental
Materials and methods
All solvents and starting materials were purchased from commercial sources
(Spectrochem, Sigma-Aldrich, India) and were used as received without further
purification. [NMP]H2PO4 was synthesized according to the literature procedure
[32] and used as a task-specific IL for the synthesis of the title compounds. Melting
points were taken in an open, glass capillary using a Stuart SMP30 melting point
apparatus and are uncorrected. The progress of the reactions was monitored by thin-
layer chromatography (TLC; E. Merck, Mumbai, India) and the developed
chromatogram was visualized under ultraviolet (UV) light and iodine vapors. The
purity and yields of the compounds was estimated on an isolated basis. Infrared (IR)
spectra were recorded on a Perkin-Elmer 100S spectrophotometer using potassium
bromide (KBr) disks. Proton nuclear magnetic resonance (1H NMR, 400 MHz)
spectra were recorded on a Bruker spectrometer using deuterated dimethylsulfoxide
(DMSO-d6 ) as a solvent; chemical shifts are reported in parts per million (d)
relative to tetramethylsilane [TMS, (CH3)4Si] as the internal standard. Elemental
analyses were performed on a Carlo-Erba model EA1108 analytical unit and were
within 0.4 % of theoretical values. Mass spectra were recorded on a Jeol JMSD-
300 spectrometer.
General procedure for the synthesis of N-methyl-2-pyrrolidonium dihydrogen
phosphate [NMP]H2PO4 acidic ionic liquid
N-Methyl-2-pyrrolidinone (1 mmol) was slowly added drop-wise to a cooled
equimolar concentration of phosphoric acid (1 mmol), and the resulting mixture was
heated at 80 °C for 24 h. The mixture was cooled to ambient temperature and
washed with ether to remove any non-ionic residues. Then the residue was dried
under high vacuum at 80 °C on a rotary evaporator until the weight of the residue
remained constant. The obtained orange-coloured, viscous IL was characterized by
1
comparing its H NMR to that of the authentic sample.
123

Recyclable task-specific acidic ionic liquid [NMP]H2PO4…
General procedure for the synthesis of thiazolo[2,3-b]quinazolinone
derivatives (4a–f)
An equimolar mixture of tetralone, substituted aromatic aldehydes, thiourea and
acidic task-specific IL [NMP]H2PO4 (10 mol%) were placed in a 10-mL pressurized
vial and subjected to MW irradiation (mono-mode, CEM Discover microwave
synthesis system at 300 W) at a temperature of 90 °C for about 2–6 min; after that
was added chloroacetyl chloride (1 mmol) and the process continued for the
appropriate time, as mentioned in Table 3. After ensuring the completion of the
reaction (monitored by TLC), 10 mL of cold water was added to the cooled reaction
mixture, the precipitated solid was filtered under vacuum and washed with distilled
water, furnishing compound (4a–f). The residue (water) containing dissolved IL was
collected by evaporation under reduced pressure.
Selected characterization data of some of the products are given below.
7-Phenyl-5,7-dihydro-6H-10-thia-7a,11-diaza-cyclopenta[b]phenanthren-8-one (4a)
1
Orange solid; IR (KBr) tmax (cm-1): 1724 (C=O), 1635 (C=N), 1598 (C=C); H
NMR (400 MHz, DMSO-d6): d 1.85–1.91 (m, 1H), 2.22–2.30 (m, 1H), 2.56–2.63
(m, 1H), 2.70–2.76 (m, 1H), 4.01–4.13 (m, 2H), 5.65 (s, 1H), 7.11 (d, J = 7.2 Hz,
1H), 7.16–7.26 (m, 2H), 7.32–7.37 (m, 5H), 7.78 (d, J = 7.6 Hz, 1H); MS (ESI) m/z:
333 (M?H); Anal. Calcd. for C20H16N2OS: C, 72.26; H, 4.85; N, 8.43; Found: C,
72.04; H, 4.62; N, 8.20.
7-(3,4-Dimethoxy-phenyl)-5,7-dihydro-6H-10-thia-7a,11-diaza-cyclopenta[b]phenan-
thren-8-one (4d) Brown solid; IR (KBr) tmax (cm-1): 1720 (C=O), 1634 (C=N),
1
1598 (C=C), 1233, 1138 (C–O–C); H NMR (400 MHz, DMSO-d6): d 1.93–1.96
(m, 1H), 2.22–2.30 (m, 1H), 2.58–2.65 (m, 1H), 2.70–2.76 (m, 1H), 3.71 (s, 3H),
3.72 (s, 3H), 4.01–4.11 (m, 2H), 5.59 (s, 1H), 6.82–6.93 (m, 3H), 7.11–7.24 (m,
3H), 7.77 (d, J = 7.2 Hz, 1H); MS (ESI) m/z: 415 (M?Na); Anal. Calcd. for
C22H20N2O3S: C, 67.33; H, 5.14; N, 7.14; Found: C, 67.52; H, 5.27; N, 7.01.
7-(3-Nitro-phenyl)-5,7-dihydro-6H-10-thia-7a,11-diaza-cyclopenta[b]phenanthren-
8-one (4f) Pale yellow solid; IR (KBr) tmax (cm-1): 1719 (C=O), 1634 (C=N),
1
1606 (C=C), 1528, 1344 (NO2); H NMR (400 MHz, DMSO-d6): d 1.81–1.90 (m,
1H), 2.26–2.34 (m, 1H), 2.57–2.65 (m, 1H), 2.71–2.79 (m, 1H), 4.02–4.13 (m, 2H),
5.93 (s, 1H), 7.12 (d, J = 7.2 Hz, 1H), 7.18–7.26 (m, 2H), 7.67–7.82 (m, 3H),
8.17–8.21 (m, 2H); MS (ESI) m/z: 378 (M?H); Anal. Calcd. for C20H15N3O3S: C,
63.65; H, 4.01; N, 11.13; Found: C, 63.50; H, 4.30; N, 11.37.
General procedure for the synthesis of thiazolo[2,3-b]quinazoline
derivatives (5a–t)
An equimolar mixture of tetralone, substituted aromatic aldehyde, thiourea and
acidic task-specific IL [NMP]H2PO4 (15 mol%) was placed in a 10-mL pressurized
vial and subjected to MW irradiation (as above) at a temperature of 90 °C for about
5–8 min; after that was added substituted phenacyl bromides/3-(2-bromoacetyl)-
2H-chromen-2-one (1 mmol), and the process continued for the appropriate time, as
123

G. Ramesh et al.
mentioned in Table 3. After ensuring completion of the reaction (monitored by
TLC), 10 mL of cold water was added to the cooled reaction mixture; the
precipitated solid was filtered under vacuum and washed with distilled water,
affording (5a–t). The residue (water) containing dissolved IL was collected by
evaporation under reduced pressure.
9-(4-Chlorophenyl)-7-phenyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline
(5a) White solid; IR (KBr) tmax(cm-1): 1604 (C=N), 824 (C–Cl); 1H NMR
(400 MHz, DMSO-d6): d 1.76 (t, J = 7.6 Hz, 1H), 2.33 (t, J = 8.0 Hz, 1H),
2.57–2.79 (m, 2H), 6.16 (s, 1H), 6.84 (d, J = 6.4 Hz, 2H), 7.17–7.46 (m, 11H), 7.65
(d, J = 6.8 Hz, 1H); MS (ESI) m/z: 427 [M?H]?; Anal. Calcd. for C26H19ClN2S:
C, 73.14; H, 4.49; N, 6.56; Found: C, 73.01; H, 4.62; N, 6.78.
9-(4-Bromophenyl)-7-phenyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline
(5h) White solid; IR (KBr) tmax(cm-1): 1603 (C=N), 578 (C–Br);
1H
NMR
(400 MHz, DMSO-d6): d 1.72–1.80 (m, 1H), 2.28–2.34 (m, 1H), 2.59 (t,
J = 8.0 Hz, 1H), 2.75–2.81 (m, 1H), 6.15 (s, 1H), 6.84 (d, J = 7.6 Hz, 2H),
7.15–7.40 (m, 9H), 7.58 (d, J = 8.4 Hz, 3H); MS (ESI) m/z: 472 [M?H]?; Anal.
Calcd. for C26H19BrN2S: C, 66.24; H, 4.06; N, 5.94; Found: C, 66.11; H, 4.28; N,
5.71.
3-(7-Phenyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-9-yl)-2H-chromen-
2-one (5n) Pale yellow solid; IR (KBr) tmax(cm-1): 1711 (C=O of lactone), 1630
(C=N); 1H NMR (400 MHz, DMSO-d6): d 1.76 (t, J = 6.4 Hz, 1H), 2.28–2.36 (m,
1H), 2.57–2.65 (m, 1H), 2.77–2.81 (m, 1H), 6.25 (s, 1H), 7.16–7.26 (m, 6H),
7.34–7.49(m, 5H), 7.64–7.89 (m, 4H); MS (ESI) m/z: 461 [M?H]?; Anal. Calcd.
for C29H20N2O2S: C, 75.63; H, 4.38; N, 6.08; Found: C, 75.91; H, 4.52; N, 6.27.
Results and discussion
Optimization of reaction conditions
Our aim to synthesize the title compounds 4 and 5 in excellent yields were achieved
by following the steps outlined (Scheme 1). The reaction mixture was exposed to
microwave irradiation at 300 W intermittently at 10-s intervals via synergistic effect
Table 1 The effect of catalysts
on the model reactions
Entry
Catalyst
Yielda (%)/time (min)
Model-1
Model-2
1
2
3
4
5
6
–
0/60
0/60
[BMIM]BF4
[BMIM]HSO4
[HMIM]HSO4
[NMP]HSO4
[NMP]H2PO4
42/60
56/60
72/60
88/60
91/60
58/60
60/60
65/60
73/60
80/60
Reactions were carried out on a
1-mmol scale (entries 1–6,
Table 1) by taking 10 mol% of
the catalyst
a
Yields are on an isolated basis
123

Recyclable task-specific acidic ionic liquid [NMP]H2PO4…
of an IL at ambient temperature (90 °C), affording the final compounds within a
very short time (2–8 min) in quantitative yields (92–98 %; Table 1).
In order to find out an efficient and suitable catalytic medium that can achieve the
final proposed structures, 4a and 5a were examined under different catalytic effects
by conducting two model reactions (model-1 and model-2) between tetralone 1
(1 mmol), benzaldehyde 2a (1 mmol), thiourea 3 (1 mmol), chloroacetic acid
(1 mmol) and 4-chloro phenacyl bromide (1 mmol). From that it was clear that
when non-imidazolium ILs were employed, the maximum and best yields of about
91 and 80 % (entry 5) and 88 and 73 % (entry 4) of conversion was observed in
cases of model-1 and model-2 reactions, respectively (entry 4 and 5, Table 1). In the
case of conventional imidazolium ILs (entries 2 and 3), the conversion was only up
to 56 and 72 % (model-1), and 60 and 65 % (model-2), but the yields were not
satisfactory. Obtaining [BMIM]BF4 was less efficient with conversion of 42 %
(model-1) and 58 % (model-2). Before testing the effect of various ILs on the model
reactions, initially, we performed the same model reactions under catalytic-free
conditions. From that, it was clear that for the transformation of the above model
reactions, the presence of catalysts should be necessary. Further, to investigate the
optimized reaction conditions, we conducted similar model reactions at different
MW frequencies at different catalyst loadings using a variety of solvents, like water,
ethanol, acetic acid and acetonitrile. In order to highlight the role of MWs in these
systems, we also conducted the model reactions under controlled conditions (in the
Table 2 Optimization of the reaction conditions for the synthesis of compounds 4a (model-1) and 5a
(model-2)
Entry Catalyst loading
[NMP]H2PO4 (mol%)
Solvent
Temp (°C)/ Time (min)
power (W)
Yielda (%)
Model-1 Model-2 Model-1 Model-2
1
5
–
–
60
30
15
9
60
30
17
15
10
12
22
9
40
91
65
91
73
88
85
98
81
20
65
85
70
80
78
38
80
54
70
83
62
72
85
92
15
33
72
62
69
71
2
10
5
–
–
3
–
70/200
70/200
70/200
70/200
70/200
90/300
90/300
90/300
90/300
4
10
15
20
30
10
15
15
15
15
15
15
15
–
5
–
12
10
20
2
6
–
7
–
8
–
9
–
10
45
30
17
20
10
10
5
10
11
12
13
14
15
Water
Ethanol
42
32
22
21
11
13
Acetic acid 90/300
Acetonitrile 90/300
–
–
100/300
120/300
Reactions were carried out on a 1-mmol scale (entries 1–13, Table 2) by taking ionic liquids at different
catalytic loads and at different reaction conditions
a
Yields are on an isolated basis
123

G. Ramesh et al.
absence of MW irradiation); from that, we noticed that rapid heat transfer facilitated
by MW heating allows the chemical transformations to proceed very rapidly
compared to that of conventional heating, thereby limiting the formation of side
products and considerable improvement in the product yield. The high heating
efficiency of microwaves provides low catalyst loading, remarkable rate enhance-
ment and a dramatic reduction in reaction time. The above results revealed that the
optimized results were obtained at 90 °C under solvent-free conditions at 10 mol%
of [NMP]H2PO4 for compound 4a (98 %) and 15 mol% of catalytic load for
Table 3 Synthesis of benzo[h]thiazolo[2,3-b]quinazolinone (4a–f) and benzo[h]thiazolo[2,3-b]quina-
zoline (5a–t) derivatives
Analogs Ar
R
Time (min) Yielda (%) Melting point (°C)
Observed Lit value
4a
4b
4c
4d
4e
4f
C6H5
–
2
4
3
4
6
6
5
6
5
5
5
8
8
7
6
6
6
7
8
8
7
7
5
5
8
8
98
96
96
95
93
92
92
94
95
94
94
92
92
96
96
93
97
94
92
96
95
96
94
97
92
94
191–193
286–288
180–182
121–123
210–212
212–214
318–320
282–294
271–272
259–260
231–233
300–301
315–317
322–323
296–298
281–283
260–261
242–244
298–299
289–291
292–294
260–261
273–275
266–268
279–281
280–281
192–194
285–287
179–181
122–124
208–210
214–216
319–320
292–294
271–273
260–262
233–236
301–303
317–318
322–324
294–296
280–282
261–263
242–244
298–300
290–291
293–294
261–263
275–277
267–269
277–279
280–282
4-OHC6H4
4-OCH3C6H4
3,4-(OCH3)2C6H3
4-ClC6H5
–
–
–
–
3-NO2C6H4
C6H5
–
5a
5b
5c
5d
5e
5f
4-ClC6H4
4-ClC6H4
4-OHC6H4
4-OH-3-OCH3C6H3 4-ClC6H4
4-OCH3C6H4
3,4-(OCH3)2C6H3
4-FC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-BrC6H4
4-BrC6H4
5g
5h
5i
4-ClC6H4
C6H5
4-OHC6H4
5j
4-OH-3-OCH3C6H3 4-BrC6H4
5k
5l
4-OCH3C6H4
3,4-(OCH3)2C6H3
4-FC6H4
4-BrC6H4
4-BrC6H4
5m
5n
5o
5p
5q
5r
5s
4-BrC6H4
C6H5
Coumarin-3-yl
Coumarin-3-yl
4-OHC6H4
4-OH-3-OCH3C6H3 Coumarin-3-yl
4-OCH3C6H4
3,4-(OCH3)2C6H3
4-FC6H4
Coumarin-3-yl
Coumarin-3-yl
Coumarin-3-yl
Coumarin-3-yl
5t
4-ClC6H4
Reaction conditions: tetralone (1, 1 mmol), substituted aromatic aldehydes (2, 1 mmol), thiourea (3,
1 mmol), chloroacetyl chloride (1 mmol) and substituted phenacyl bromides/3-(2-bromoacetyl)-2H-
chromen-2-one (1 mmol), [NMP]H2PO4 (10 and 15 mol% for the synthesis of compounds 4 and 5,
respectively), MW irradiation (300 W), temperature (90 °C), 2–8 min, yield (92–98 %)
a
Yields are on an isolated basis
123

Recyclable task-specific acidic ionic liquid [NMP]H2PO4…
compound 5a (92 %) at a microwave frequency of 300 W. The results are illustrated
in Table 2.
Utilizing the above optimized conditions, the scope and efficiency of the
procedure was explored, whereby the procedure successfully synthesized struc-
turally diverse thiazolo[2,3-b]quinazolinone 4 (a–f) and thiazolo[2,3-b]quinazoline
5 (a–t) derivatives in excellent yields (92–98 %) within a very short reaction time
(2–8 min; summarized in Table 3). All the synthesized compounds were well
established by spectral and elemental analysis and also by comparison with their
literature melting points [27, 28] (see Supporting file). A plausible mechanism for
the formation of the fused thiazolo[2,3-b]quinazolinone and thiazolo[2,3-b]quina-
zoline derivatives is illustrated in Scheme 2.
Recovery and recyclability of the catalyst
One of the important issues in green synthesis is catalyst recovery. To further
investigate the recyclability of the IL [NMP]H2PO4, distilled water (10 mL) was
added to the cooled reaction mixture after completion of the reaction. The separated
crude solid product was filtered and washed twice with distilled water (2 9 5 mL).
The residue (water) containing dissolved IL with halide impurities was collected by
evaporating the solvent under reduced pressure and washed with dichloromethane
(2 9 10 mL). Further, to the IL was added tert-butanol to strip out the halide
impurities (chloride and bromide) as volatile tert-butyl halides, which can be
pumped out. Also, water was added to the IL to drive off tert-butyl halides remains
as azeotropes. Finally, the regenerated halide-free IL (orange colored viscous IL)
was dried under reduced pressure and titrated against AgNO3 to confirm the absence
of halides. Then, the catalytic activity of recycled IL was checked for about five
cycles at the same optimised conditions for the same model reactions (Table 2); the
results are summarized in Table 4. From the results, it was confirmed that the
recycled IL showed considerable catalytic activity and can be reused effectively up
to four cycles without loss of its catalytic activity. But, after performing the 5th
recyclable cycle, a considerable decrease in the yields was observed.
Scheme 2 Proposed reaction mechanism for the synthesis of title compounds 4 and 5 in the presence of
[NMP]H2PO4 ionic liquid (IL)
123

G. Ramesh et al.
Table 4 Reusability of [NMP]H2PO4 in the synthesis of title compounds 4a and 5a
Run
Reaction time (min)
Yielda (%)
Model-1
Model-2
1
2
3
4
5
2
2
2
2
2
98
97
94
91
76
88
82
81
83
65
Reactions were carried out on 1-mmol scale (entries 1–4, Table 4) by taking 10 mol% of the catalyst at
optimized conditions
a
Yields are on an isolated basis
Conclusions
In summary, our newly developed protocol using task-specific acidic IL [NMP]
H2PO4 under microwave irradiation in a one-pot process via an MCR approach is an
efficient, simple, rapid and environmentally benign procedure for the quantitative
and qualitative synthesis of a series of thiazolo[2,3-b]quinazolinone and thia-
zolo[2,3-b]quinazoline derivatives. This method is complementary to the classical
method and offers advantages over conventional approaches in terms of yield, time
and operational simplicity. The non-imidazolium IL [NMP]H2PO4 is recyclable and
can be reused as a catalyst, effective for about four cycles.
Acknowledgments We thank the Director at the, National Institute of Technology, Warangal for
providing facilities to carry out the research. The author (RG) thanks the Ministry of Human Resource
Development for awarding a senior research fellowship, and the authors GR and RV give thanks to the
University Grants Commission (UGC) for providing research fellowships.
References
1. P. Anastas, J.C. Warner, Green Chemistry: Theory and Practice (Oxford University Press, Oxford,
1998), p. 135?xi
2. P.T. Anastas, T.C. Williamson, Green Chemistry: Frontiers in Chemical Synthesis and Processes,
edn (Oxford University Press, Oxford, 1998), p. 364?xvii
3. P.T. Anastas, M.M. Kirchhoff, Acc. Chem. Res. 35, 686 (2002)
4. A. Domling, W. Wang, K. Wang, Chem. Rev. 112, 3083 (2012)
5. J. Aleman, S. Cabrera, Chem. Soc. Rev. 42, 774 (2013)
6. J. Zhu, H. Bienyame, Multi Component Reactions (Wiley-VCH, Weinheim, 2005)
7. F.R. Charati, Chin. Chem. Lett. 25, 169 (2014)
8. C.O. Kappe, Acc. Chem. Res. 33, 879 (2000)
9. M.B. Gawande, V.D.B. Bonifacio, R. Luque, P.S. Branco, R.S. Varma, ChemSusChem 7, 24 (2014)
10. D. Dallinger, N.Y. Gorobets, C.O. Kappe, Org. Lett. 5, 1205 (2003)
11. M. Nuchter, B. Ondruschka, W. Bonrath, A. Gum, Green Chem. 6, 128 (2004)
12. H.R. Shaterian, M. Aghakhanizadeh, Chin. J. Catal. 34, 1690 (2013)
13. H.R. Shaterian, M. Aghakhanizadeh, Phosphorus Sulfur Silicon Relat. Elem. 188, 1064 (2013)
14. H. Singh, S. Kumari, J.M. Khurana, Chin. Chem. Lett. 25, 1336 (2014)
15. L. Suresh, Y. Poornachandra, S. Kanakaraju, C. Ganesh Kumar, G.V.P. Chandramouli, Org. Biomol.
Chem. 13, 7294 (2015)
123

Recyclable task-specific acidic ionic liquid [NMP]H2PO4…
16. J. Sindhu, H. Singh, J.M. Khurana, Synth. Commun. 45, 202 (2015)
17. H.M. Majid, H. Elaheh, S.B. Yahya, K. Khadijeh, T. Maryam, H. Nastaran, J. Mol. Catal. A Chem.
392, 173 (2014)
18. H.R. Shaterian, M. Aghakhanizadeh, Res. Chem. Intermed. 40, 1655 (2014)
19. B. Pan, R. Huang, L. Zheng, C. Chen, S. Han, D. Qu, M. Zhu, P. Wei, Eur. J. Med. Chem. 46, 819
(2011)
20. M. Ashok, B.S. Holla, N.S. Kumari, Eur. J. Med. Chem. 42, 380 (2007)
21. S. Maddila, G.L.V. Damu, E.O. Oseghe, O.A. Abafe, C. Venakata Rao, P. Lavanya, J. Korean Chem.
Soc. 56, 334 (2012)
22. L.S. Ramesh, A.B. Charusheela, B.W. Jyoti, Med. Chem. Res. 22, 1884 (2013)
23. T.P. Selvam, V.J. Palanirajan, Malay. J. Pharm. Sci. 8, 45 (2010)
24. E.E. Flefel, M.A. Salama, M. El-Shahat, Phosphorus Sulfur Silicon Relat. Elem. 182, 1739 (2007)
25. B.S. Holla, B.S. Rao, B.K. Sarojini, P.M. Akberali, Eur. J. Med. Chem. 39, 777 (2004)
26. A.A. Abu-Hashem, M.M. Youssef, H.A.R. Hussein, J. Chin. Chem. Soc. 58, 41 (2011)
27. B. Janardhan, B. Srinivas, B. Rajitha, P.A. Crooks, Tetrahedron Lett. 55, 224 (2014)
28. B. Janardhan, K. Manjulatha, B. Srinivas, B. Rajitha, N. Muralikrishna, A. Sadanandam, RSC Adv. 4,
22866 (2014)
29. G. Ramesh, B. Janardhan, B. Rajitha, Res. Chem. Intermed. (2014). doi:10.1007/s11164-014-1879-z
30. B. Janardhan, V. Krishnaiah, B. Rajitha, A.C. Peter, Chin. Chem. Lett. 25, 17 (2014)
31. B. Janardhan, B. Rajitha, Chin. Chem. Lett. 23, 1015 (2012)
32. H. Guo, X. Li, J.L. Wang, X.H. Jin, X.F. Lin, Tetrahedron 66, 8300 (2010)
123