Three component one-pot synthesis of 1-aryl-4-benzo[f]quinoline derivatives in glycerol

Article abstract of DOI:10.14233/ajchem.2015.18100

A series of 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)one derivatives were synthesized by one-pot muticomponent reaction of Meldrum's acid with benzaldehyde, naphthalene-2-amine in glycerol. Glycerol, a new green organic solvent, it not only acts as a catalyst but also as a recyclable solvent by significantly enhancing the intramolecular cyclization. When compared with classical methods, this method has the advantages of milder reaction conditions, good yields, easy processing and environmental benignity. All compounds were characterized by elemental analysis, FT-IR and 1H NMR spectra.

Full text of DOI:10.14233/ajchem.2015.18100

Asian Journal of Chemistry; Vol. 27, No. 3 (2015), 1053-1055
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.18100
Three Component One-Pot Synthesis of 1-Aryl-4-benzo[f]quinoline Derivatives in Glycerol
1,*
2
1
XUE-MEI WANG , XIN MA and HAI-LONG MA
1College of Mechanical and Electronical Engineering, Lanzhou University of Technology, Qilihe Langongping Road 287, Lanzhou 730050,
Gansu Province, P.R. China
2College of Chemistry and Chemical Engineering, Lanzhou University, Tianshui South Road 222, Lanzhou 730000, Gansu Province, P.R. China
*Corresponding author: Tel: +86 931 2869462; E-mail: teacherwang0105@163.com
Received: 29 May 2014;
Accepted: 13 August 2014;
Published online: 19 January 2015;
AJC-16723
A series of 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)one derivatives were synthesized by one-pot muticomponent reaction of Meldrum's
acid with benzaldehyde, naphthalene-2-amine in glycerol. Glycerol, a new green organic solvent, it not only acts as a catalyst but also as
a recyclable solvent by significantly enhancing the intramolecular cyclization. When compared with classical methods, this method has
the advantages of milder reaction conditions, good yields, easy processing and environmental benignity.All compounds were characterized
by elemental analysis, FT-IR and 1H NMR spectra.
Keywords: One-pot synthesis, Benzo[f]quinoline derivatives, Glycerol.
There have been some reports on the syntheses of 1-aryl-
1,2-dihydrobenzo[f]quinolin-3(4H)one derivatives, such as
two-component reaction9,10. Zhang et al.11 have completed the
synthesis of these compounds by a three-component one-pot
reaction at refluxing temperature catalyzed by triethylbenzyl-
ammonium chloride (TEBA) in water. Although water is low
cost and facile, as well as environmental benignity, most of
organic compounds are hydrophobe and triethylbenzyl-
ammonium chloride still has some environmental problems,
so these disadvantages limited the applied scope of reaction
in water.
Recently, we have reported the synthesis of benzo[f]quino-
line derivatives in PEG-400 media by one-pot reaction and
have gotten good results12. In this communication, we report a
simple and effective method for synthesis of a series of quino-
line derivatives by one-pot multicomponent reaction of
Meldrum’s acid (1) with benzaldehyde (2), naphthalene-2-
amine (3) in glycerol media. 1-Aryl-1,2-dihydrobenzo[f]-
quinolin-3(4H)-one derivatives (4) were obtained in high yields
(Fig. 1).
INTRODUCTION
As a organic reaction medium, the exploration of glycerol
is still very limited, but because of its physical and chemical
properties of low toxicity, non-corrosibility, non-combus-
tibility, involatile and wide liquid range, glycerol rightly meet
the most requirements of ideal green solvents1. It was shown2,3
that glycerol, as reaction medium, can not only increase the
reaction rate, but also improve the reaction selectivity. Because
of glycerol's lower solubility in non-polar organic solvents
and miscible with water, the separation of the products can
be realized by organic solvent extraction method or water
washing.
Quinoline is a kind of benzopyridine compound with six-
membered nitrogen-fused heterocycle. A further combination
with aromatic rings or heterocycles makes it become aza-
polycyclic compounds like naphthyridine and acridine,
which have conjugated structure with rigid plane. Its strong
fluorescence and various bioactivities can act as embedded
molecule into DNA, fluorescent probe and drug synthesis, etc.,
which has a broad application in medicine and molecular
biology4,5. Its multi-hydroxy homologs that contain non-planar
structure and active carbonyl groups make this kind of
compounds possible when further application is used in
material science and life science, especially as new synthesized
drugs. The application of nitrogen-fused heterocycles has been
promising in the aspect of sterilization, antimalaria and anti-
neoplasm6-8.
EXPERIMENTAL
All reagents were obtained commercially and used without
further purification. Meldrum's acid 1 were synthesized accor-
ding to the literature methods13. Melting points were measured
on an XT-4 electrothermal micromelting-point apparatus and
the thermometer was uncorrected. C, H and N analyses were
obtained using an Elemental Vario-EL automatic elemental

1054 Wang et al.
Asian J. Chem.
1-(4-Fluorophenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4e): Yield: 85 %, m.p. 254-256 °C. 1H NMR (400
MHz, DMSO-d6, δ): 2.67(d, J = 16.0 Hz, 1H, CH2), 3.19 (dd,
J = 16.0, 7.6 Hz, 1H, CH2), 5.06 (d, J = 7.6 Hz, 1H, CH), 7.08
(d, J = 8.0 Hz, 2H, ArH), 7.08 (d, J = 8.0 Hz, 1H, ArH), 7.26
(d, J = 8.0 Hz, 2H, ArH), 7.33-7.49 (m, 2H, ArH), 7.67-7.79
(m, 1H, ArH), 7.85-7.92 (m, 2H, ArH), 10.46 (s, 1H, NH). IR
(KBr, νmax, cm-1): 3204, 3068, 2995, 2908, 1679. Anal. Calcd
for C19H14NOF: C 78.33, H 4.84, N 4.81; found C 78.54, H
4.79, N 4.83.
1-(4-Methoxyphenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4f): Yield: 84 %, m.p. 241-242 °C. 1H NMR (400
MHz, DMSO-d6, δ): 2.67 (d, J = 16.4 Hz, 1H, CH2), 3.14 (dd,
J = 16.4, 7.2 Hz, 1H, CH2), 3.72 (s, 3H, CH3), 4.98 (d, J = 7.2
Hz, 1H, CH), 6.86 (d, J = 8.8 Hz, 2H, ArH), 7.05 (d, J = 8.8
Hz, 2H, ArH), 7.28 (d, J = 8.8 Hz, 2H, ArH), 7.33-7.41 (m,
1H, ArH), 7.45-7.52 (m, 1H, ArH), 7.84 (d, J = 8.8 Hz, 1H,
ArH), 7.88 (d, J = 8.8 Hz, 2H, ArH), 10.37 (s, 1H, NH). IR
(KBr, νmax, cm-1): 3203, 3086, 2994, 2952, 2906, 1686. Anal.
Calcd for C20H17NO2: C 79.19, H 5.65, N 4.62; found C 79.05,
H 5.62, N 4.57.
Ar
O
NH2
glycerol
O
+
Ar-CHO +
O
N
H
O
O
2
1
3
4
Fig. 1. One-pot synthesis of 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)one
derivatives
analysis instrument. FT-IR spectra were recorded using KBr
pellets on a Digilab Merlin FT-IR spectrophotometer. 1H NMR
spectra were recorded, on a Varian Mercury plus-400 instru-
ment using DMSO or CDCl3 as solvents and TMS as internal
standard.
General synthetic procedure for compounds (4a-i): A
mixture of meldrum's acid 1 (2 mmol), aromatic aldehyde 2
(2 mmol), naphthalene-2-amine 3 (2 mmol) in glycerol (2 g)
was stirred for 12-16 h at 110 °C. The progress of the reaction
was monitored by TLC. After completion of the reaction, the
reaction mixture was filtered and the precipitate was washed
with water. The crude products were purified by recrystalli-
zation from ethanol (95 %) to give products 4a-i.
1-Phenyl-1,2-dihydrobenzo[f]quinolin-3(4H)one (4a):
Yield: 81 %, m.p. 257-259 °C. 1H NMR (400 MHz, DMSO-
d6, δ): 2.65 (d, J = 16.0 Hz, 1H, CH2), 3.20 (dd, J = 16.0, 7.6
Hz, 1H, CH2), 5.05 (d, J = 7.6 Hz, 1H, CH), 7.12 (d, J = 8.0
Hz, 1H,ArH), 7.24-7.35 (m, 4H,ArH), 7.43-7.50 (m, 3H,ArH),
7.64 (d, J = 8.0 Hz, 1H, ArH), 7.89-7.96 (m, 2H, ArH), 10.45
(s, 1H, NH). IR (KBr, νmax, cm-1): 3196, 3061, 2938, 1685
cm-1.Anal. Calcd for C19H15NO: C 83.49, H 5.53, N 5.12; found
C 83.63, H 5.57, N 5.17.
1-(4-Chlorophenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4b): Yield: 85 %, m.p. 243-244 °C. 1H NMR (400
MHz, DMSO-d6, δ): 2.53 (d, J = 16.8. Hz, 1H, CH2), 3.19 (dd,
J = 16.8 Hz, 8.0 Hz, 1H, CH2), 5.02 (d, J = 4.4 Hz, 1H, CH),
7.15 (d, J = 8.4 Hz, 2H, ArH), 7.24-7.32 (m, 4H, ArH), 7.46
(t, J = 7.6 Hz, 1H, ArH), 7.82 (t, J = 7.6 Hz, 1H, ArH), 7.86-
7.90 (m, 2H, ArH), 10.46 (s, 1H, NH). IR (KBr, νmax, cm-1):
3196, 3080, 3048, 2942, 2909, 1679 cm-1. Anal. Calcd for
C19H14NOCl: C 74.15, H 4.58, Cl 11.52, N 4.55; found C 74.32,
H 4.55, Cl 11.57, N 4.52.
1-(2,4-Dichlorophenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4c): Yield: 83 %, m.p. 269-270 °C. 1H NMR (400
MHz, DMSO-d6, δ): 2.55 (d, J = 16.4 Hz, 1H, CH2) 3.27 (dd,
J = 16.4, 7.6 Hz, 1H, CH2), 5.31 (d, J = 7.6 Hz, 1H, CH), 7.09
(d, J = 8.4, 1H, ArH), 7.16 (d, J = 8.4, 1H, ArH), 7.24-7.31
(m, 2H,ArH), 7.42-7.50 (m, 1H,ArH), 7.59-7.64 (m, 1H,ArH),
7.73 (s, 1H,ArH), 7.86-7.96 (m, 2H,ArH), 10.52 (s, 1H, NH).
IR (KBr, νmax, cm-1): 3167, 3078, 3046, 2949, 2923, 1684.
Anal. Calcd for C19H13NOCl2: C 66.68, H 3.83, N 4.09; found
C 66.53, H 3.87, N 4.12.
1-(4-Bromophenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4d): Yield: 82 %, m.p. 245-246 °C. 1H NMR (400
MHz, DMSO-d6, δ): 2.63 (d, J = 16.0 Hz, 1H, CH2), 3.18 (dd,
J = 16.0, 7.2 Hz, 1H, CH2), 5.02 (d, J = 7.2 Hz, 1H, CH), 7.07
(d, J = 8.0 Hz, 2H, ArH), 7.22-7.35 (m, 4H, ArH), 7.49 (t, 1H,
ArH), 7.86 (d, J = 8.8 Hz, 1H, ArH), 7.82-7.89 (m, 2H, ArH),
10.43 (s, 1H, NH). IR (KBr, νmax, cm-1): 3198, 3076, 3043,
2967, 2912, 1679.Anal. Calcd for C19H14NOBr: C 64.79, H 4.01,
Br 22.69, N 3.98; found C 64.61, H 4.04, Br 22.66, N 3.83.
1-(2-Nitrophenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4g): Yield: 83 %, m.p. 244-246 °C. 1H NMR (400
MHz, DMSO-d6, δ): 2.61 (d, J = 16.8 Hz, 1H, CH2), 3.38 (dd,
J = 16.4, 8.0 Hz, 1H, CH2), 5.46 (d, J = 5.2 Hz, 1H, CH), 6.84
(d, J = 4.0 Hz, 1H, ArH), 7.31-7.56 (m, 6H, ArH), 7.85-7.91
(m, 3H, ArH), 10.8 (s, 1H, NH). IR (KBr, νmax, cm-1): 3215,
3079, 2989, 2944, 1678.Anal. Calcd for C19H14N2O3: C 79.69,
H 4.43, N 8.80; found C 71.53, H 4.41, N 8.83.
1-(3-Nitrophenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4h): Yield: 86 %, m.p. 270-271 °C. 1H NMR (400
MHz, DMSO-d6, δ): 2.66 (d, J = 16.4 Hz, 1H, CH2), 3.26 (dd,
J = 16.0, 7.2 Hz, 1H, CH2), 5.31 (d, J = 4.40 Hz, 1H, CH),
7.33-7.58 (m, 5H, ArH), 7.84-8.13 (m, 5H, ArH), 10.56
(s, 1H, NH). IR (KBr, νmax, cm-1): 3198, 3086, 2992, 2933,
1686. Anal. Calcd for C19H14N2O3: C 79.69, H 4.43, N 8.80;
found C 71.57, H 4.46, N 8.83.
1-(4-Nitrophenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4i): Yield: 84 %, m.p. 257-258 °C. 1H NMR (400
MHz, DMSO-d6, δ): 2.65 (d, J = 16.4 Hz, 1H, CH2), 3.42 (dd,
J = 16.4, 7.6 Hz, 1H, CH2), 5.51 (d, J = 5.2 Hz, 1H, CH), 6.85
(d, J = 8.4 Hz, 2H, ArH), 7.12-7.35 (m, 4H, ArH), 7.34 (t, J =
7.6 Hz, 1H, ArH), 7.76 (d, J = 7.6 Hz, 1H, ArH), 7.90-8.07
(m, 2H, ArH), 10.58 (s, 1H, NH). IR (KBr, νmax, cm-1): 3205,
3069, 2995, 2939, 1682.Anal. Calcd for C19H14N2O3: C 79.69,
H 4.43, N 8.80; found C 71.57, H 4.41, N 8.76.
RESULTS AND DISCUSSION
We tried the synthesis of 4a with reactive substrates of
aromatic aldehyde, naphthalene-2-amine and Meldrum's acid
under different reaction conditions. It was indicated that the
yield of 1-phenyl-1,2-dihydrobenzo[f]quinolin-3(4H)one (4a)
was been effected by the time and temperature of reaction.
The yield was better at higher temperature than that under the
conditions of lower temperature and short time. Thereby, we
deduced that the desired 1-phenyl-1,2-dihydrobenzo[f]quinolin-
3(4H)one (4a) can be obtained at 81 % yield in glycerol for
16 h. In addition, the yield will increase gradually with the

Vol. 27, No. 3 (2015)
Three Component One-Pot Synthesis of 1-Aryl-4-benzo[f]quinoline Derivatives in Glycerol 1055
Conclusion
A series of 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)one
increase of the temperature of reaction, the maximal yield was
obtained at 110 °C.
To validate the feasibility of the reaction, we chose diffe-
rent aromatic aldehyde derivatives to react with naphthalene-
2-amine and Meldrum's acid, respectively (Table-1). The results
show that all reactions have good yields whether benzaldehyde
or benzaldehyde substituted by substitutents in the ortho, meta
and para positions, which are either electron-withdrawing
groups (such as halide) or electron-donating groups (such as
alkoxyl group). The influence brought by electronic effect of
the substitutents, was not too great for the yields of reactions.
It indicated that the experimental conditions have excellent
selectivity, we did not obtain the bis-substituted products.
derivatives were synthesized by three-component one-step
reaction in glycerol. Compared with the traditional two-
component method, this method has the advantages of milder
reaction conditions, good yields, easy processing and
environmental benignity, etc. Compared to the reaction in water
by noxious catalyzer (such as triethylbenzylammonium
chloride), glycerol is more environmental friendliness, because
the dual role of glycerol as reaction solvent and catalyst and
glycerol can be recycled. Compared with the one-pot reaction
in PEG-400, this method could significantly shorten the reac-
tion time, improve the yield and product separation is more
convenient and even the reaction solvent is low-cost and easily
accessible.A simple and green but effective synthesis of benzo-
[f]quinoline derivatives using glycerol as reaction medium is
reported.
TABLE-1
SYNTHESIS OF 1-ARYLBENZO[f]QUINOLINE
DERIVATIVES 4 IN GLYCEROL AT 110 °C
Product
4a
4b
4c
4d
4e
4f
4g
4h
Ar
Time (h)
16
Yield (%)
C6H5
81
85
83
82
85
84
83
86
84
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Reaction conditions: 1 (2 mmol), 2 (2 mmol), 3 (2 mmol), glycerol
(2 g)
In summary, This work describes an efficient and environ-
mentally friendly approach for the one-pot multicomponent
synthesis of 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)-one
derivatives in glycerol. The present method offers attractive
features such as excellent yields, simple reaction conditions,
environmentally benign and easily work up. Moreover, glycerol
not only acts as a catalyst but also as a clean solvent by signi-
ficantly enhancing the intramolecular cyclization.
The conceivable reaction mechanism for compound 4 had
been previously described12.