An environmentally benign, green, and efficient ionic liquid catalyzed synthesis of Quinoline derivatives via Knoevenagel condensation

Article abstract of DOI:10.1002/jhet.3754

The present investigation is in the interest of one-pot, environmentally friendly and efficient protocol for the synthesis of quinoline derivatives from 2-aminoarylketones and active methylene compounds in the presence of L-proline and ionic liquid 1,3-di

Full text of DOI:10.1002/jhet.3754

Received: 24 May 2019
DOI: 10.1002/jhet.3754
Revised: 4 September 2019
Accepted: 6 September 2019
A R T I C L E
An environmentally benign, green, and efficient ionic
liquid catalyzed synthesis of Quinoline derivatives via
Knoevenagel condensation
Syed Tasqeeruddin
| Yahya I. Asiri
Department of Pharmaceutical Chemistry,
College of Pharmacy, King Khalid
University, Abha, Saudi Arabia
Abstract
The present investigation is in the interest of one-pot, environmentally friendly
and efficient protocol for the synthesis of quinoline derivatives from
2-aminoarylketones and active methylene compounds in the presence of
L-proline and ionic liquid 1,3-dimethylimidazolium methyl sulfate [MMIm]
[MSO4]. The Ionic liquid which is used as a catalyst can be reused several
times. The results obtained by using [MMIm][MSO4] were also compared with
those described in the literature. The advantages of the method are shorter
reaction time, milder conditions, easy workup and better yields. The catalyst
[MMIm][MSO4] can be recovered for the subsequent reactions and reused
without any appreciable loss of efficiency. This method of synthesis widens the
applicability of Ionic liquids in heterocyclic compounds.
Correspondence
Syed Tasqeeruddin, Department of
Pharmaceutical Chemistry, College of
Pharmacy, King Khalid University. Abha
62529, Saudi Arabia.
Email: drsyedtasqeeruddin@gmail.com
active anticonvulsant agents[15] (Figure 1). Further, they
are also known to possess anti-inflammatory,[16] anti-
bacterial,[17] and anticancer,[18] activities.
1 | INTRODUCTION
Literature survey revealed that Knoevenagel products
associated with important biological activities, therefore,
they are employed in the synthesis of pharmacological
products and in many therapeutic drugs.[1–3] The
Knoevenagel condensations are an important C C bond-
forming reactions which are generally carried out in the
presence of surfactants,[4] zeolites,[5] heterogeneous
catalysts,[6] and bases such as potassium fluroiodide, eth-
ylenediamine, piperdine, and Lewis acids.[7] Many
organic chemists showed great interest in the synthesis of
compounds containing quinoline moieties due to their
versatile pharmacological properties such as antimalarial
potentials (e.g., Quinine-I[8] and Chloroquine-II[9]). The
other derivatives like Ciprofloxacin-III, Moxifloxacin-
IV,[10] and Mefloquine-V[11] are best known,
antitubercular agents. Compounds like 4-substituted
2,3-diarylquinoline derivatives-VI are important for the
treatment of Parkinson's[12,13] and Alzheimer's dis-
eases.[14] Chloroquinolinyl-hydrazone derivatives–VII is
It is pertinent here to mention that several methods
have been developed for the synthesis of quinoline deriv-
atives. Zdenko Hans Skraup[19] reported the first formal
synthesis of quinoline derivatives in 1880. Wang et al. in
2011[20] presented the synthesis of 2-methylquinoline
derivatives. Quinoline derivatives have also been synthe-
sized by the ultrasound technique.[21] The above-
mentioned reactions suffer from several drawbacks like
harsh reaction conditions, high temperature, and volatile
organic solvents and consist of many multiple steps.
Skraup-Doebner-Von Miller,[22] Pfitzinger-Borsche,[23,24]
and Esmaeilpoura and Javidi[25] reported many synthetic
routes. The synthesis which involves the condensation of
o-haloacetophenones with urea or primary amines,[26]
requires high temperature and long reaction time (150ꢀC,
48 hours). Currently, rapid, eco-friendly and solvent-free
synthetic methods have become powerful techniques
because these methods are free from using hazard
J Heterocyclic Chem. 2019;1–8.
wileyonlinelibrary.com/journal/jhet
© 2019 Wiley Periodicals, Inc.
1

2
TASQEERUDDIN AND ASIRI
FIGURE 1 Biologically active quinoline derivatives
chemicals and they are inexpensive.[27] Therefore, from
the chemical and biological point of view, the develop-
ment of environmentally benign organic reactions has
become mandatory.
the synthesis of quinoline derivatives via Knoevengal
condensation. The results are reported here. Ionic liq-
uid [MMIm][MSO4] was prepared by following the lit-
erature procedure.[33]
Recently Ionic liquids got lots of attention in many
organic syntheses because of their unusual properties,
including negligible vapor pressure, broad liquid tem-
perature range, and high capacity as specific sol-
vents.[28] The use of Ionic liquids in the place of
harmful and volatile solvents makes the organic synthe-
sis environmentally benign.[29] In many Knoevenagel
condensations, Ionic liquids have been used as a sol-
vent or as a catalyst, because they accelerate the reac-
tion, making the work-up process easier and allowing
their recycling.[30–32] In this article, we employed Ionic
liquid 1,3-dimethylimidazolium methyl sulfate [MMIm]
[MSO4] as a green, efficient and recyclable catalyst for
2 | RESULTS AND DISCUSSION
A mixture of 2-aminoacetophenone 1 (1.0 mL, 10 mmol),
acetylacetone 2 (1.3 mL, 12 mmol), undried Ionic liquid
1,3-dimethylimidazolium methyl sulfate [MMIm][MSO4]
and catalytic amount of L-proline (25 mol%) were mixed
in a Schlenk flask (25 mL) and the mixture was stirred
carefully at 90ꢀC until the reaction was finished. The
completion of the reaction was checked by TLC. The
crude solid was collected after the evaporation of the sol-
vent under reduced pressure and the resulting residue
was purified by column chromatography (Scheme 1).

TASQEERUDDIN AND ASIRI
3
SCHEME 1 Synthesis of 1-(2-methylquinolin-3-yl)ethanone
To check the effect of L-proline in the presence of
Ionic liquid 1,3-dimethylimidazolium methyl sulfate
[MMIm][MSO4], the reaction was carried out with a vari-
ant percentage of L-proline. First, we tried the reaction
in the absence of L-proline however, after 28 hours
at 90ꢀC, no product had been formed (Table 1). Thus,
the combination of Ionic liquid [MMIm][MSO4] and
L-proline proved to be the best for the synthesis of
1-(2,4-dimethylquinolin-3-yl)ethanone. The optimum
concentration of catalyst L-proline required in the above
reaction (Scheme 1) was also studied by changing the
amount of catalyst from 0, 5, 10, 15, 20, 25, and 30 mol%
in Ionic liquid [MMIm][MSO4] under reflux at 90ꢀC. The
product was obtained in 0%, 65%, 75%, 85%, 90%, 98%,
and 92% yield, respectively. The best yield of the product
was obtained when 25 mol% of the L-proline was used.
Therefore, all the reactions were carried out in 25 mol%
of L-proline and Ionic liquid [MMIm][MSO4] under
reflux condition at 90ꢀC. The results are shown in
Table 1.
We then continued to optimize the model reaction
(Scheme 1) by detecting the efficiency of the Ionic liquid
[MMIm][MSO4] and other solvents. The reaction was
carried out in the absence of solvent and catalyst how-
ever, after 28 hours at 90ꢀC, no product had been formed.
In solvents like Ethanol, tetrahydrofuran, toluene, and
1,4-dioxane (Table 2, entries 2-6), the reaction took a lon-
ger time with moderate yield of the products, whereas in
Ethanol, Glycerol and Triethanolamine in the presence
of catalyst Pyridinium p-toluene sulfonate 20 mol%
(Table 2, entries 7-9), even after longer reaction time, no
product had been observed. Conducting the same reac-
tion in solvents, triethanolamine, PEG-600, and glycerol
with 20 mol% pyridinium acetate catalyst (Table 2,
entries 10-12), again only less amount of the product was
obtained. However, when the same reaction was
conducted with Ionic liquid [MMIm][MSO4] and
25 mol% L-proline catalyst there was a significant
increase in the yield of the product in a shorter period.
Thus, it is concluded that Ionic liquid [MMIm][MSO4]
TABLE 1 Optimization of reaction conditions using different catalytic amounts
Run
L-proline (mol %)
T (ꢀC)
90
Time (h)
Yielda (%)
1
2
3
4
5
6
7
0
28
0
5
90
6
65
75
85
90
98
92
10
15
20
25
30
90
3
90
2
90
1
90
30 min
30 min
90
Note. Reaction condition: 2-aminoacetophenone 1 (1.0 mL, 10 mmol), acetylacetone 2 (1.3 mL, 12 mmol), L-proline and [MMIm][MSO4].
aYields of the isolated products.

4
TASQEERUDDIN AND ASIRI
TABLE 2 Optimization of reaction conditions using various solvents and different catalyst for the synthesis of
1-(2,4-dimethylquinolin-3-yl)ethanone derivatives
Run
1
Solvent
Catalyst (mol %)
Time (h)
Yielda (%
Nil
10
-
-
28
20
20
24
18
20
12
10
10
4
2
Ethanol
MgO (10)
3
Ethanol
MgSO4 (10)
15
4
Tetrahydrofuran
Toluene
P-toluenesulfonic acid (20)
P-toluenesulfonic acid (20)
P-toluenesulfonic acid (20)
Pyridinium p-toluene sulfonate (20)
Pyridinium p-toluene sulfonate (20)
Pyridinium p-toluene sulfonate (20)
Pyridinium acetate (20)
Pyridinium acetate (20)
Pyridinium acetate (20)
L-proline (25)
Trace
40
5
6
1,4-dioxane
Ethanol
58
7
Nil
Nil
Nil
60
8
Glycerol
9
Triethanolamine
Triethanolamine
PEG-600
10
11
12
13
4
65
Glycerol
8
60
[MMIm][MSO4]
30 min
98
Note. Reaction condition: 2-aminoacetophenone 1 (1.0 mL, 10 mmol), acetylacetone 2 (1.3 mL, 12 mmol).
aYields of the isolated products.
and L-proline is the best combination for the synthesis of
Quinoline derivatives via Knoevenagel condensation. The
results were summarized in the Table 2.
To evaluate the scope and the feasibility of this reaction
for various 2-aminoacetophenone (1a-j) and substituted
active methylene compounds (2a-j) under optimized con-
ditions. A series of 2-aminoacetophenone bearing either
electron releasing or electron-withdrawing groups reacted
successfully to afford a wide range of substituted quinoline
derivatives in good to excellent yield in shorter reaction
SCHEME 2 Synthesis of 1-(2-methylquinolin-3-yl)ethanone derivatives from substituted 2-aminoacetophenone and active methylene
compounds in L-proline and ionic liquid [MMIm][MSO4]

TASQEERUDDIN AND ASIRI
5
TABLE 3 Synthesis of quinoline derivatives in undried [MMIm][MSO4] containing L-proline (25 mol%)
Melting point (ꢀC)
Time
(min)
Entry Name
1-(2-methylquinolin-3-yl) Ethanone
Structure
Yielda(%) Found
Oil
Reported
3a
3b
3c
3d
30
98
95
97
95
--
1-(2,4-dimethylquinolin-3-yl)
Ethanone
45
30
30
131-132 --
1-(2-methyl-
4-phenylquinolin-3-yl)ethanone
109-111 113[34]
(2,4-dimethylquinolin-3-yl)(phenyl)methanone
1-(2-ethyl-4-methylquinolin-3-yl)propan-1-one
Ethyl 2,4-dimethylquinoline-3-carboxylate
Oil
Oil
--
--
3e
42
97
3f
40
40
95
95
111-112 --
3g
1-(4-(4-chlorophenyl)-2-methylquinolin-3-yl)
ethanone
151-153 151[34]
(Continues)

6
TASQEERUDDIN AND ASIRI
TABLE 3 (Continued)
Melting point (ꢀC)
Time
(min)
Entry Name
Structure
Yielda(%) Found
Reported
166-167 --
3h
1-(2-methyl-6-nitro-
45
95
4-phenylquinolin-3-yl)ethanone
3i
1-(6-chloro-4-(2-chlorophenyl)-
2-methylquinolin-3-yl)ethanone
35
96
101-102
77-79
3j
1-(6-chloro-4-(2-fluorophenyl)-
2-methylquinolin-3-yl)ethanone
30
96
--
Note. Reaction condition: Condensation of substituted 2-aminoacetophenone 1a-j (1.0 mL, 10 mmol), substituted acetylacetone 2a-j (1.3 mL, 12 mmol) in the
presence of [MMIm][MSO4] and catalytic amount of L-proline (20 mol%).
aYields of the isolated products.
time. We explored further the electronic effect of various
substituents present on the 2-aminoacetophenone. We
noticed that various 2-aminoacetophenone having both
electron-donating and electron-withdrawing substituents
are equally facile for the reaction, and gave the
corresponding quinoline derivatives in very good yields.
We have observed most of the 2-aminoacetophenone bear-
ing electron-donating reacted in shorter reaction time
and gave the corresponding quinoline derivatives in
good yields than 2-aminoacetophenone bearing electron-
withdrawing substituents. (Scheme 2) and the results were
summarized in Table 3.
The efficiency of Ionic liquid [MMIm][MSO4] was also
determined by comparing with other Ionic liquids used
in the Knoevenagel condensation reactions reported ear-
lier in the literature. The results summarized in Table 4,
proved the advantages of our method in terms of reaction
time and yield of the products as compared with those
reported methods.
TABLE 4 Screening of efficiency of ionic liquid [MMIm]
[MSO4] with other ionic liquids used in the Knoevenagel
condensation
Run
Ionic liquid
[emim][BF4]
[Hmim]Tfa
EAN
Time (h)
Yielda (%)
97[35]
91[36]
94[37]
96[38]
3 | CONCLUSION
1
2
3
4
12
4
In conclusion, we have developed an expedient, efficient,
facile, clean and environmentally benign methodology
for the synthesis of quinoline derivatives by using an
inexpensive, easily prepared ionic liquid. The advantages
3
[bmim]PF6
6
aYields of the isolated products.

TASQEERUDDIN AND ASIRI
7
of this environmentally benign and safe protocol include
a simple reaction setup, very mild reaction conditions,
high product yields, short reaction times, and the possi-
bility of reusing the catalyst.
(2,4-dimethylquinolin-3-yl)(phenyl)methanone (3d):
Yield 95; Yellow color solid.1H-NMR (400 MHz, CDCl3) δ
8.10-8.06 (m, 1H), 8.04-8.01 (m, 1H), 7.87-7.82 (m, 2H),
7.77-7.71 (m, 1H), 7.67-7.54 (m, 2H), 7.52-7.44 (m, 2H),
2.55 (s, 3H), 2.48 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ
198.9, 154.1, 147.1, 140.7, 136.5, 134.1, 132.1, 129.8, 129.5,
129.4, 129.2, 126.6, 126.2, 123.5, 24.2, 17.9. LCMS: m/z
261.12 [M+]; anal. calc. for C18H15NO: C, 82.73; H,
5.79; N, 5.36; found: C, 82.75; H, 5.81; N. 5.38.
4 | EXPERIMENTAL
All the commercially available chemicals and reagents
were used without further purification. Column chroma-
tography was carried out on silica gel (200-400 mesh).
Melting points were determined using a Buchi melting
point B-545 apparatus and are uncorrected. TLC checking
was done on glass plates coated with Silica Gel-G and spot-
1-(2-ethyl-4-methylquinolin-3-yl)propan-1-one
(3e):
1
Yield 97; light yellow oil. H NMR (400 MHz, CDCl3) δ
8.04-8.02 (m, 1H), 7.94-7.91 (m, 1H), 7.68-7.65 (m, 1H),
7.51-7.48 (m, 1H), 2.79-2.77 (m, 4H), 2.48 (s, 3H), 1.32 (t,
3H, J = 7.3 Hz), 1.22 (t, 3H,J = 7.1 Hz); 13C NMR
(100 MHz, CDCl3) δ 209.3, 157.3, 147.2, 138.8, 135.5,
134.4, 131.6, 129.3, 129.5, 126.3, 125.4, 123.8, 117.2, 115.3,
38.6, 30.1, 15.4, 13.8, 7.7. LCMS: m/z 227.13 [M+]; anal.
calc. for C15H17NO: C, 79.26; H, 7.54; N, 6.16; found: C,
79.29; H, 7.56; N. 6.18.
1
ting was done by using iodine as well as a UV lamp. H-
NMR spectra were recorded on a Gemini-200 and AV-400
instruments operating at 200 and 400 MHZ, respectively.
General procedure for the synthesis of quinoline
derivatives (3a-j): A mixture of 1 (10 mmol), 2 (12 mmol)
and L-proline (25 mol%) in undried [MMIm][MSO4]
(2 mL) was stirred in a round-bottomed flask and
refluxed for a period of 0.5 hours. After the completion of
the reaction (as shown by TLC analysis), the reaction
mixture was extracted with ethyl acetate (3 × 2 mL) and
the pooled organic extract was concentrated under vac-
uum, affording a pure solid.
Ethyl 2,4-dimethylquinoline-3-carboxylate (3f): Light
1
yellow solid, mp 111-112ꢀC. H-NMR (400 MHz, CDCl3)
δ 7.98 (d, 1H, J = 8.3 Hz), 7.93 (d, 1H), 7.67 (t, 1H), 7.53
(t, 1H), 4.45 (q, 2H), 2.72 (s, 3H), 2.63 (s, 3H), 1.45 (t,
3H); 13C-NMR (100 MHz, CDCl3) δ 189.71, 159.85, 149.5,
138.21, 132.58, 131.71, 130.2, 129.56, 129.4, 127.61,
127.26, 126.21, 114.2, 44.36, 31.45, 26.48. LCMS: m/z
229.11 [M+]; anal. calcd. for C14H15NO2: C, 73.30; H,
6.55; N, 6.09; found: C, 73.34; H, 6.59; N. 6.11.
1-(2-methylquinolin-3-yl)ethanone (3a): Yield 98;
Light yellow oil.1H NMR (400 MHz, CDCl3) δ 8.48 (s,
1H), 8.04 (d, J = 8.5 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H),
7.78-7.76 (m, 1H), 7.57-7.53 (m, 1H), 2.91 (s, 3H), 2.71 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 199.9, 157.6, 148.2,
138.2, 131.7, 131.1, 128.5, 128.3, 126.7, 125.6, 29.2, 25.6.
LCMS: m/z 185.08 [M+]; anal. calc. for C12H9NO: C,
77.80; H, 5.98; N, 7.53; found: C, 77.81; H, 5.99; N. 7.56.
1-(2,4-dimethylquinolin-3-yl)ethanone (3b): Yield 95;
1-(4-(4-chlorophenyl)-2-methylquinolin-3-yl)ethanone
1
(3g): Yield 95; Yellow color solid. H-NMR (400 MHz,
CDCl3) δ 8.08 (d, 1H, J = 8.4 Hz), 7.76-7.71 (m, 1H),
7.57-7.56 (m, 1H,), 7.52-7.46 (m, 3H), 7.32-7.30 (m, 2H),
2.73 (s, 3H), 2.06 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ
204.7, 153.7, 147.6, 142.8, 135.7, 134.4, 133.6, 131.3, 130.6,
129.9, 128.6, 126.4, 125.5, 124.1, 32.6, 23.3. LCMS: m/z
295.10 [M+]; anal. calc. for C18H14ClNO: C, 73.10; H,
4.77; N, 4.74; found: C, 73.12; H, 4.79; N. 4.76.
1
Light yellow oil. H-NMR (400 MHz, CDCl3) δ 7.93 (d,
1H, J = 8.5 Hz), 7.85 (dd, 1H), 7.63-7.59 (m, 1H),
7.46-7.42 (m, 1H), 2.53 (s, 3H), 2.48 (s, 3H), 2.47 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 206.4, 152.3, 146.4, 138.2,
135.4, 129.3, 129.2, 126.1, 125.7, 123.4, 32.4, 23.3, 15.1.
LCMS: m/z 199.1 [M+]; anal. calc. for C13H13NO: C,
78.35; H, 6.57; N, 7.02; found: C, 78.36; H, 6.58; N. 7.03.
1-(2-methyl-4-phenylquinolin-3-yl)ethanone (3c): Yield
1-(2-methyl-6-nitro-4-phenylquinolin-3-yl)ethanone
1
(3h): Yield 97; Yellow color solid. H-NMR (400 MHz,
CDCl3) δ 8.59 (d, 1H, J = 8.4 Hz), 8.51-8.48 (m, 1H),
8.22 (d, 1H, J = 9.3), 7.61-7.58 (m, 3H), 7.40-7.38 (m,
2H), 2.73 (s, 3H), 2.03 (s, 3H); 13C-NMR (100 MHz,
CDCl3) δ 204.7, 157.7, 149.6, 145.8, 145.7, 136.4, 133.6,
132.3, 131.6, 130.9, 129.8, 129.6, 129.4, 129.2, 128.6,
124.4, 123.5, 123.1, 116.6, 31.6, 24.3. LCMS: m/z 306.10
[M+]; anal. calc. for C18H14N2O3: C, 70.58; H, 4.61; N,
9.15; found: C, 70.61; H, 4.63; N. 9.17.
97; Yellow color solid, mp. 109-111ꢀC (113-114)[33]
;
1H-NMR (400 MHz, CDCl3) δ 8.07 (d, 1H, J = 8.3 Hz),
7.75-7.72 (m, 1H), 7.60 (d, 1H, J = 8.3 Hz), 7.50-7.48 (m,
3H), 7.45-7.43 (m, 1H), 7.35-7.34 (m, 2H), 2.70 (s, 3H),
1.97 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 205.6, 153.4,
147.7, 144, 135.2, 134.9, 130.1, 130.0, 128.8, 128.7, 128.6,
126.6, 126.3, 125.0, 31.8, 23.7. LCMS: m/z 261.12 [M+];
anal. Calc. for C18H15NO: C, 82.73; H, 5.79; N, 5.36;
found: C, 82.76; H, 5.81; N. 5.38.
1-(6-chloro-4-(2-chlorophenyl)2-methylquinolin3-yl)
1
ethanone (3i): Light yellow solid, mp 101-102ꢀC. H-
NMR (400 MHz, CDCl3) δ 8.04 (d, 1H, J = 9 Hz), 7.67
(dd, 1H), 7.61-7.58 (m, 1H), 7.52-7.48 (m, 1H), 7.44-7.41
(m, 1H), 7.28 (d, 1H), 7.25-7.23 (m, 1H), 2.72 (s, 3H),

8
TASQEERUDDIN AND ASIRI
2.17 (s, 3H); 13C-NMR (100 MHz, CDCl3) δ 204.2,
154, 145.3, 140.2, 135.3, 133.1, 133, 132.5, 131.8,
131, 130.6, 130.4, 130, 127.2, 125.1, 124.3, 31.1, 23.7.
LCMS: m/z 329.04 [M+]; anal. calcd. for
C18H13Cl2NO: C, 65.46; H, 3.96; N, 4.23; found: C,
65.47; H, 3.97; N. 4.24.
[15] S. Kumar, S. Bawa, S. Drabu, R. Kumar, L. Machawal, Acta.
Poloniae. Pharmaceutica. 2010, 67, 567.
[16] G. Roma, M. Di Braccio, G. Grossi, F. Mattioli, M. Ghia, Eur.
J. Med. Chem. 2000, 35, 1021.
[17] A. K. Sadana, Y. Mirza, K. R. Aneja, O. Prakash, Eur. J. Med.
Chem. 2003, 38, 533.
[18] A. R. Martirosyan, R. Rahim-Bata, A. B. Freeman, C. D. Clarke,
R. L. Howard, J. S. Strobl, Biochem. Pharmacol. 2004, 68, 1729.
[19] Z. H. Skraup, Ber. 1880, 13, 2086.
1-(6-chloro-4-(2-fluorophenyl)2-methylquinolin3-yl)
1
ethanone (3j): Light yellow solid, mp 77-79ꢀC. H-NMR
[20] Y. Wang, J. Ai, Y. Wang, Y. Chen, L. Wang, G. Lui, M. Geng,
A. Zhang, J. Med. Chem. 2011, 54, 2127.
[21] E. Kowsari, M. Mallakmohammadi, Ultrason. Sonochem. 2011,
18, 447.
(400 MHz, CDCl3) δ 8.02 (d, 1H, J = 9.1 Hz), 7.68 (dd,
1H), 7.59-7.52 (m, 1H), 7.40-7.38 (m, 1H), 7.35-7.22 (m,
3H), 2.70 (s, 3H), 2.16 (s, 3H); 19F NMR (376 MHz, CDCl3)
δ-112.3;13C-NMR (100 MHz, CDCl3) δ 204.44, 160.2,
158.2, 153.8, 145.5, 137.4, 136.2, 132.7, 132.2, 132, 131.6,
131.54, 131.1, 130.4, 125.6, 124.7, 124.5, 124.3, 122, 121.8,
116.2, 116, 31.2, 23.6. LCMS: m/z 313.07 [M+]; anal. calcd.
for C18H13ClFNO: C, 68.90; H, 4.17; N, 4.45; found: C,
68.91; H, 4.18; N. 4.46.
[22] F. W. Bergstrom, Chem. Rev. 1944, 35, 77.
[23] M. A. Shvekhgeimer, Chem. Heterocycl. Comp. 2004, 40, 257.
[24] N. P. Buu-Hoi, R. Royer, N. D. Xuong, P. J. Jacquignon, Org.
Chem. 1953, 18, 1209.
[25] M. Esmaeilpoura, J. Javidi, J. Chin. Chem. Soc. 2015, 62, 328.
[26] C. Qi, Q. Zheng, R. Hau, Tetrahedron 2009, 65, 1316.
[27] a) Caddick, S. Tetrahedron, 1995, 51, 10403. b) Lidstrom, P.;
Tierney, J.; Wathey, B.; Westman, J. Tetrahedron, 2001, 57,
9225. c) Verma, R. S. Green Chem., 1999, 1, 43.
[28] C. F. Poole, J. Chromatog. A 2004, 1037, 49.
[29] Welton, T.; Wasserscheid, P. Ionic Liquids in Synthesis Wiley-
VCH, Weinheim, Germany, 2003, 1, 37.
[30] C. Yue, A. Mao, Y. Wei, M. Lü, Catal. Commun. 2008, 9, 1571.
[31] W. Wang, W. Cheng, L. Shao, C. Liu, J. Yang, J. Henry, Kinet.
Catal. 2009, 50, 186.
[32] D.-Z. Xu, Y. Liu, S. Shi, Y. A. Wang, Green Chem. 2010,
12, 514.
ACKNOWLEDGMENTS
The authors would like to express their gratitude to King
Khalid University, Saudi Arabia for providing administra-
tive and technical support. The research has no funding
support, but as it is a part of employment and employee
name is KING KHALID UNIVERSITY.
[33] E. Gómez, B. González, N. Calvar, E. Tojo, A. Rodríguez,
J. Chem. Eng. Data 2006, 51, 2096.
[34] J. S. Yadav, B. V. S. Reddy, P. Sreedhar, R. S. Rao, K. Nabaiah,
Synthesis 2004, 2004, 2381.
ORCID
Syed Tasqeeruddin https://orcid.org/0000-0002-5253-
7606
[35] Y. Wang, Z. Shang, T. Wu, J. Fan, X. Chen, J. Mol. Catal. A:
Chemical 2006, 253, 212.
REFERENCES
[36] N. B. Darvatkar, A. R. Deorukhkar, S. V. Bhilare,
M. M. Salunkhe, Synth. Commun. 2006, 36, 3043.
[37] S. A. R. Mulla, A. Sudalai, M. Y. Pathan, S. A. Siddique,
S. M. Inamdar, S. S. Chavan, R. S. Reddy, RSC Adv. 2012, 2,
3525.
[1] G. A. Kraus, M. E. J. Krolski, Org. Chem. 1986, 51, 3347.
[2] L. F. Tietze, Pure Appl. Chem. 2004, 76, 1967.
[3] F. Liang, Y. Pu, T. Kurata, J. Kido, H. Nishide, Polymer 2005,
46, 3767.
[4] D. S. Bose, A. V. J. Narsaiah, Chem. Res. (S). 2001, 36.
[5] P. Leelavathi, S. R. Kumar, J. Mol. Catal. A: Chem. 2005, 99, 240.
[6] Y. Goa, P. Wu, T. Tatsumi, J. Catal. 2004, 224, 107.
[7] J. McNulty, J. A. Steere, S. Wolf, Tetrahedron Lett. 1998, 39, 8013.
[8] R. E. McGrew, Encyclopedia of Medical History, McGrew-Hills,
New York 1985 166.
[38] P. Formentın, H. Garcıa, A. J. Leyva, Mol. Cat. A: Chemical
2004, 214, 137.
SUPPORTING INFORMATION
Additional supporting information may be found online in
the Supporting Information section at the end of this article.
[9] P. B. Bloland, Drug Resistance in Malaria, World Health Orga-
nization 2001 12.
[10] A. S. Ginsber, J. H. Grosset, W. R. Bishai, Lancet Infect. Dis.
2003, 3, 432.
[11] S. Jayaprakash, Y. Iso, B. Wan, S. G. Franzblau,
A. P. Kozikowski, Chem. Med. Chem. 2006, 1, 593.
[12] R. Ghodsi, A. Zarghi, B. Daraei, M. Hedayati, Bioorg. Med.
Chem. 2010, 18, 1029.
[13] A. Van Gool, P. S. Aisen, P. Eikeleboom, Neurol. J. 2003, 250, 788.
[14] P. S. Aisen, K. A. Schafer, M. Grundman, E. Pfeiffer, M. Sano,
K. I. Davis, M. R. Farlow, S. Jin, R. G. Thomas, L. J. Thal,
JAMM 2003, 289, 2819.
How to cite this article: Tasqeeruddin S,
Asiri YI. An environmentally benign, green, and
efficient ionic liquid catalyzed synthesis of
Quinoline derivatives via Knoevenagel
condensation. J Heterocyclic Chem. 2019;1–8.
https://doi.org/10.1002/jhet.3754