One-pot synthesis of benzoquinoline and coumarin derivatives using Meldrum's acid in three-component reactions

Article abstract of DOI:10.1007/s11164-012-0762-z

A series of 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)-one derivatives and 4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin derivatives have been synthesized by one-pot multicomponent reaction of Meldrum's acid with benzaldehyde, naphthalene-2-amine, or cyclohexanedione in PEG-400. The method has the advantages of mild reaction conditions, good yields, and easy processing, and is environmentally benign.

Full text of DOI:10.1007/s11164-012-0762-z

Res Chem Intermed
DOI 10.1007/s11164-012-0762-z
One-pot synthesis of benzoquinoline and coumarin
derivatives using Meldrum’s acid in three-component
reactions
•
•
•
Xue-Mei Wang He-Lin Ye Zheng-Jun Qaun
Xi-Cun Wang
Received: 3 June 2012 / Accepted: 6 August 2012
Ó Springer Science+Business Media B.V. 2012
Abstract A series of 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)-one derivatives
and 4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin derivatives have
been synthesized by one-pot multicomponent reaction of Meldrum’s acid with
benzaldehyde, naphthalene-2-amine, or cyclohexanedione in PEG-400. The method
has the advantages of mild reaction conditions, good yields, and easy processing,
and is environmentally benign.
Keywords One-pot synthesis Á Meldrum’s acid Á Multicomponent reaction Á
Synthesis Á Benzo[f]quinoline derivatives Á Hexahydrocoumarin derivatives
Introduction
Compared with conventional methods of organic synthesis, multicomponent
reactions (MCR) have the advantages of high-selectivity, good yields, milder
reaction conditions, and simple work-up procedures, among others. The probability
that three or more molecules collide in the right direction and at the appropriate
energy is very low, and most known multicomponent one-pot reactions can be
regarded more precisely as domino or tandem reactions. Thus, a vast number of
diverse compounds can be obtained in a parallel synthesis [1–4].
X.-M. Wang (&)
School of Mechanical and Electronic Engineering, Lanzhou University of Technology,
Qilihe Langongping Road 287, Lanzhou 730050, Gansu, China
e-mail: teacherwang0105@163.com
H.-L. Ye Á Z.-J. Qaun Á X.-C. Wang
Key Laboratory of Eco-Environment-Related Polymer Materials Ministry of Education, China,
Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering,
Northwest Normal University, Anning East Road 967, Lanzhou 730070, Gansu, China
123

X. Wang et al.
Meldrum’s acid is a very active substrate frequently used in MCRs [5]. Most
MCRs based on utilization of Meldrum’s acid involve fundamental reactions, for
example domino Knoevenagel–hetero-Diels–Alder reactions [6], domino Wittig–
Knoevenagel–pseudo-Diels–Alder reactions [7], modified Hantzsch synthesis [8],
Yonemitsu reaction (domino Knoevenagel–Michael) [9, 10], domino (Knoevena-
gel)–cycloaddition–solvolysis-I-MCR (isonitrile-MCR) [11], and Biginelli-like
reactions [12]. In most of these reactions Meldrum’s acid first condenses with
carbonyl moieties, ultimately leading to a substituted propionic acid extension of the
molecules. Domino Knoevenagel–isonitrile-cycloaddition is a unique subclass,
because the major product retains two carboxyl groups of the masked malonic acid
moiety. Some MCRs cannot be clearly classified, for example, when Meldrum’s
acid reacts with unsaturated carbonyl compounds in a Knoevenagel condensation
and ring closure is followed by condensation. In other cases Meldrum’s acid acts as
a Michael donor with its highly acidic methylene moiety in an aldol-type reaction.
PEG-400 is inexpensive, thermally stable, non-volatile, non-toxic, and easily
degradable. It has emerged as a green solvent for organic reactions and has been
attracting much attention [13–16].
Benzoquinoline derivatives have excellent biological and medical activity, for
example antibacterial [17], anti-hypertension [18], antimalarial [19], and antivirus
[20]. Hexahydrocoumarins are a series of natural products with physiological activity;
they have been widely investigated as laser dyes, and for anticancer and antivirus
activity [21–23]. There has, therefore, been much interest in the synthesis of
benzoquinoline and hexahydrocoumarin derivatives in recent years. There have been
several reports [24–27] of the synthesis of 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)-
one derivatives. One method was two-component reaction of a Schiff base and
Meldrum’s acid; another was two-component reaction of naphthalene-2-amine and an
a,b-unsaturated Meldrum’s acid. Zhang et al. [28] recently reported the synthesis of
heterocyclic acetanilide 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)-one derivatives
by three-component one-pot reaction of benzaldehyde, naphthalene-2-amine, and
Meldrum’s acid at reflux temperature catalyzed by triethylbenzylammonium chloride
in water. Although water is inexpensive, simple to use, and environmentally benign,
most organic compounds are hydrophobic, a disadvantage which has limited the
scope of reactions in water. Analogously, there have been reports of the synthesis of
4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin derivatives [29–31] in
organic solvent or in water, by use of a catalyst, or microwave-induced in ethanol.
The former methods have the problem of pollution; in the latter inconvenient work-up
could be a problem. Recently, Li et al. [32] and Du et al. [33] reported the synthesis of
4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin derivatives in water and
an ionic liquid, respectively, but ionic liquids are relatively expensive and there is
uncertainly about their toxicity. There is, therefore, no environmentally benign
method with mild reaction conditions, good yields, easy processing for synthesis of
1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)-one derivatives and 4-aryl-7,7-dimethyl-
5-oxo-3,4,5,6,7,8-hexahydrocoumarin derivatives.
In this communication, we report a simple and effective method for synthesis
of a series of quinoline derivatives and hexahydrocoumarin derivatives by one-pot
MCR of Meldrum’s acid (1) with benzaldehyde (2), naphthalene-2-amine (3) or
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One-pot synthesis of benzoquinoline and coumarin derivatives
Scheme 1 One-pot synthesis of benzoquinoline derivatives and coumarin derivatives
5,5-dimethyl-1,3-cyclohexanedione (5) in PEG-400. 1-Aryl-1,2-dihydrobenzo[f]quino-
lin-3(4H)-one derivatives (4) or 4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydro-
coumarin derivatives (6) were obtained in high yields (Scheme 1).
Results and discussion
We tried the synthesis of 4b with the reactive substrates 4-chlorobenzaldehyde,
naphthalene-2-amine, and Meldrum’s acid under different reaction conditions. The
results are presented in Table 1. The yield of 1-(4-chlorophenyl)-1,2-dihydro-
benzo[f]quinolin-3(4H)-one (4b) was affected by the time and temperature of the
reaction. The yield was better under reflux than at lower temperature for a short
time. We deduced that the desired 1-(4-chlorophenyl)-1,2-dihydrobenzo[f]quinolin-
3(4H)-one (4b) can be obtained in 84 % yield in PEG-400 under reflux for 14 h. In
addition, the yield increases gradually with increasing temperature of the reaction;
the maximum yield was obtained at 100 °C.
To investigate the feasibility of the reaction, we chose benzaldehyde with
different substitutents to react with naphthalene-2-amine and Meldrum’s acid
(Table 2). The results showed that all reactions resulted in good yields irrespective
of whether benzaldehyde or benzaldehyde with substituents in the ortho, meta, or
para positions was used, or whether the substituents were electron-withdrawing (for
Table 1 Yields of 4b in PEG-
400 under different reaction
conditions
Entry
t/°C
Time/h
Yield/ %a
1
2
3
4
5
6
7
r.t.
40
40
35
30
20
12
14
16
73
79
81
83
81
84
84
60
80
100
100
100
Reaction conditions: 1
(2.0 mmol), 2 (2.0 mmol),
3 (2.0 mmol), PEG 400 (2 g)
a
Isolated yields
123

X. Wang et al.
Table 2 Synthesis of 1-arylbenzo[f]quinoline derivatives 4a in PEG-400
Entry
Ar
Time/h
Product
Yield/ %a
Mp (Lit)/ °C
1
2
3
4
5
6
7
8
9
C6H5
20
16
14
16
14
18
15
15
14
4a
4b
4c
4d
4e
4f
80
84
81
80
85
82
83
86
82
259–261/(256–261) [28]
242–244/(242–243) [27]
268–270/(259–261) [28]
244–245/(244–247) [28]
255-257/(255-258) [28]
240–242/(241–243) [28]
245–247
4-ClC6H4
2,4-Cl2C6H3
4-BrC6H4
4-FC6H4
4-CH3OC6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
4g
4h
4i
269–270
256–257
Reaction conditions: 1 (2.0 mmol), 2 (2.0 mmol), 3 (2.0 mmol), PEG-400 (2 g),100 °C, under reflux
a
Isolated yields
example halide) or electron-donating (for example alkoxy group) groups. The
electronic effect of substituents on the benzaldehyde had little effect on the yields of
the reactions. This indicates the selectivity of the experimental conditions is
excellent. Also, we did not obtain the bis substituted products.
On the basis of product structure, Wang et al. [27] believe that formation of
compound 4 can be explained by the possible mechanism presented in Scheme 2.
They found that 1-aryl-1,2-dihydrobenzo[f]quinolin-3(4H)-one derivatives were
readily obtained when arylidene Meldrum’s acids was treated with naphthalene-2-
amine in PEG-400. This suggested that Michael addition occurs place in the
mechanism mentioned above.
Scheme 2 Mechanism of the Michael addition reaction
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One-pot synthesis of benzoquinoline and coumarin derivatives
Table 3 Yields of 6a in PEG-
400 under different reaction
conditions
Entry
t/°C
Time/h
Yield/ %a
1
2
3
4
5
6
7
50
60
70
70
70
70
80
6
6
4
5
6
7
6
45
72
65
70
81
81
81
Reaction conditions: 1
(2.0 mmol), 2 (2.0 mmol), 4
(2.0 mmol), PEG-400 (2 g)
a
Isolated yields
Table 4 Synthesis of hexahydrocoumarin derivatives 6a in PEG-400
Entry
Ar
Time/h
Product
Yield/ %a
Mp(Lit)/°C
1
2
3
4
5
6
4-ClC6H4
6
6
6
6
6
6
6a
6b
6c
6d
6e
6f
81
75
83
72
70
68
160–162/(162–163) [32]
107–109/(106–108)[32]
132–134/(133–135) [32]
178–180/(181–183) [32]
129–131/(128–130) [33]
182–184/(179–181) [33]
4-CH3C6H4
4-NO2C6H4
3-CH3O-4-OHC6H3
4-CH3OC6H4
4-(CH3)2NC6H4
Reaction conditions: 1 (2.0 mmol), 2 (2.0 mmol), 3 (2.0 mmol), PEG-400 (2 g), 70 °C, 6 h
a
Isolated yields
Similarly, we tried synthesis of 6a with the reactive substrates 4-chlorobenzal-
dehyde, Meldrum’s acid, and 5,5-dimethyl-1,3-cyclohexanedione under different
reaction conditions. The results shown in Table 3 indicate that the yield of
4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin (6a) was affected
by the time and temperature of reaction. We concluded that 6a can be obtained in
81 % yield in PEG-400 at 70 °C for 14 h.
To demonstrate the efficiency and the applicability of this method, we performed
the reaction with a variety of substituted benzaldehydes in PEG-400 at 70 °C
(Table 4). As shown in Table 4, a series of 4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-
hexahydrocoumarin derivatives 6 bearing electron-withdrawing groups (for exam-
ple halide) or electron-donating groups (for example hydroxy and alkoxy) were
synthesized by reaction of Meldrum’s acid with 2 and 5 to give the corresponding
products 6 in good yields under the same reaction conditions. Therefore, we
concluded that the electronic nature of the substituents has no significant effect on
this reaction.
On the basis of the structure of the products, Margaretha [29] believed the
reaction route to compound 6 may be the mechanism presented in Scheme 3.
Meldrum’s acid and benzaldehyde react to form the arylidene Meldrum acid. The
arylidene Meldrum acid and 5,5-dimethyl-1,3-cyclohexanedione produce an
intermediate by Michael addition, and the intermediate then isomerizes to form a
ring, eliminating acetone and carbon dioxide, to give compound 6.
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X. Wang et al.
Scheme 3 The synthetic mechanism for compound 6
In this procedure, PEG-400 not only acts as a phase-transfer catalyst but also as a
clean solvent by significantly enhancing intramolecular cyclization. Moreover,
PEG-400 is a recyclable reagent. In the reaction of 4a, we recycled the PEG-400
three times and the reaction proceeded cleanly with good yields (85, 83, and 82 %),
although a little weight loss of PEG-400 was observed from cycle to cycle because
of mechanical loss. Further studies to develop the new clean environmentally
benign reagent for synthesis of biologically active compounds are in progress.
In summary, this work describes an efficient and environmentally friendly
approach for one-pot multicomponent synthesis of 1-aryl-1,2-dihydrobenzo[f]quin-
olin-3(4H)-one derivatives and 4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydro-
coumarin derivatives, by use of Meldrum’s acid in PEG-400. The method has very
attractive features, for example excellent yields, simple reaction conditions, and
easy work up; it is also environmentally benign. Moreover, participation of
Meldrum’s acid makes this process highly efficient.
Experimental
All reagents were obtained commercially and used without further purification.
Meldrum’s acid 3 was synthesized in accordance with literature methods [34].
Melting points were measured on an XT-4 Electrothermal micromelting-point
apparatus, and are uncorrected. IR spectra were recorded using KBr pellets on a
Digilab Merlin FT-IR spectrophotometer. NMR spectra were recorded at 400 (1H)
and 100 (13C) MHz, respectively, on a Varian Mercury plus-400 instrument using
DMSO as solvent and TMS as internal standard.
General synthetic procedure for compounds (4a–i)
A mixture of benzaldehyde 1 (2 mmol), naphthalene-2-amine (2 mmol), and
Meldrum’s acid 3 (2 mmol) in PEG-400 (2 g) was stirred for 14–20 h under reflux.
The progress of the reaction was monitored by TLC. After completion of the
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One-pot synthesis of benzoquinoline and coumarin derivatives
reaction, the reaction mixture was filtered and the precipitate washed with water.
The crude products were purified by recrystallization from ethanol (95 %) to give
products 4a–i.
1-Phenyl-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4a)
1
Yield 79 %, m.p. 259–261 °C. H NMR (400 MHz, DMSO-d6) d: 2.62 (d, J =
16.0 Hz, 1H, CH2), 3.17 (dd, J = 16.0, 7.6 Hz, 1H, CH2), 5.02 (d, J = 7.6 Hz, 1H,
CH), 7.06–7.94 (m, 11H, ArH), 10.42 (s, 1H, NH). IR (KBr) m: 3194, 3064, 2937,
1684, 1625, 1603, 1522, 1493, 1473, 1452, 1426, 1388, 1334, 1243, 1197, 1182,
1166, 1075, 1031, 965, 906, 863, 820, 760, 747, 722, 698 cm-1
.
1-(4-Chlorophenyl)-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4b)
Yield 83 %, m.p. 242–244 °C.1H NMR (400 MHz, DMSO-d6) d: 2.50 (d, J = 16.8.
Hz, 1H, CH2), 3.18 (dd, J = 16.8 Hz, 8.0 Hz, 1H, CH2), 5.03 (d, J = 4.4 Hz, 1H,
CH), 7.10 (d, J = 8.4 Hz, 2H, ArH), 7.26–7.35 (m, 4H, ArH), 7.41 (t, J = 7.6 Hz,
1H, ArH), 7.80 (t, J = 7.6 Hz, 1H, ArH), 7.85–7.88 (m, 2H, ArH), 10.44 (s, 1H, NH).
IR (KBr) m: 3194, 3078, 3042, 2941, 2907, 1677, 1625, 1490, 1382, 1323, 1242,
1092, 1013, 955, 901, 831, 733, 685, 645, 594, 521, 476, 426 cm-1
.
1-(2,4-Dichlorophenyl)-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4c)
1
Yield 81 %, m.p. 268–270 °C. H NMR (400 MHz, DMSO-d6) d: 2.56(d, J =
16.4 Hz, 1H, CH2) 3.24 (dd, J = 16.4, 7.6 Hz, 1H, CH2), 5.28 (d, J = 7.6 Hz, 1H,
CH), 6.50–7.92 (m, 9H, ArH), 10.50 (s, 1H, NH). IR (KBr) m: 3164, 3075, 3046,
2948, 2927, 1683, 1627, 1603, 1587, 1557, 1525, 1468, 1427, 1383, 1344, 1323,
1249, 1200, 1160, 1142, 1100, 1049, 961, 905, 887, 861, 824, 799, 780, 746,
722 cm-1
.
1-(4-Bromophenyl)-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4d)
1
Yield 80 %, m.p. 244–245 °C. H NMR (400 MHz, DMSO-d6) d: 2.62 (d, J =
16.0 Hz, 1H,CH2),3.16(dd,J = 16.0, 7.2 Hz,1H, CH2),5.02(d, J = 7.2 Hz, 1H, CH),
7.08 (d, J = 8.0 Hz, 2H, ArH), 7.25–7.36(m, 4H, ArH), 7.45 (t, 1H, ArH), 7.80 (d,
J = 8.8 Hz, 1H, ArH), 7.82–7.88 (m, 2H, ArH), 10.40 (s, 1H, NH). IR (KBr)
m: 3196, 3078, 3044, 2965, 2909, 1677, 1625, 1606, 1587, 1524, 1488, 1473, 1425,
1383, 1327, 1290, 1259, 1244, 1182, 1170, 1073, 1011, 958, 832, 816, 799, 782,
736 cm-1
.
1-(4-Fluorophenyl)-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4e)
1
Yield 85 %, m.p. 255–257 °C. H NMR (400 MHz, DMSO-d6) d: 2.64(d, J =
16.0 Hz, 1H, CH2), 3.14 (dd, J = 16.0, 7.6 Hz, 1H, CH2), 5.02 (d, J = 7.6 Hz, 1H,
CH), 7.02–7.86 (m, 10H, ArH), 10.40 (s, 1H, NH). IR (KBr) m: 3199, 3069, 2993,
123

X. Wang et al.
2907, 1677, 1626, 1603, 1522, 1505, 1472, 1427, 1387, 1343, 1322, 1276, 1241,
1194, 1155, 1103, 1029, 970, 833, 818, 797, 783, 750, 736 cm-1
.
1-(4-Methoxyphenyl)-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4f)
1
Yield 82 %, m.p. 240–242 °C. H NMR (400 MHz, DMSO-d6) d: 2.62 (d, J =
16.4 Hz, 1H, CH2), 3.12 (dd, J = 16.4, 7.2 Hz, 1H, CH2), 3.68 (s, 3H, CH3), 4.94
(d, J = 7.2 Hz, 1H, CH), 6.82 (d, J = 8.8 Hz, 2H, ArH), 7.02 (d, J = 8.8 Hz,
2H, ArH), 7.26 (d, J = 8.8 Hz, 2H, ArH), 7.30–7.36 (m, 1H, ArH), 7.42–7.47
(m, 1H, ArH), 7.82 (d, J = 8.8 Hz, 1H, ArH), 7.84 (d, J = 8.8 Hz, 2H, ArH), 10.34
(s, 1H, NH). IR (KBr) m: 3205, 3089, 2991, 2955, 2902, 2833, 1687, 1625, 1604,
1581, 1508, 1463, 1417, 1388, 1346, 1317, 1251, 1177, 1158, 1111, 1032, 830, 818,
796, 780, 744 cm-1
.
1-(2-Nitrophenyl)-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4g)
1
Yield 83 %, m.p. 245–247 °C. H NMR (400 MHz, DMSO-d6) d: 2.59 (d, J =
16.8 Hz, 1H,CH2),3.37(dd,J = 16.4, 8.0 Hz,1H, CH2),5.44(d, J = 5.2 Hz, 1H, CH),
6.79 (d, J = 4.0 Hz, 1H, ArH), 7.34–7.57 (m, 6H, ArH), 7.88–8.05 (m, 3H, ArH), 10.6
(s, 1H, NH). IR (KBr) m: 3217, 3078, 2941, 2141, 1954, 1820, 1679, 1626, 1602, 1518,
1475, 1387, 1347, 1238, 1111, 1026, 965, 854,818, 750, 701, 633, 510, 432 cm-1
.
1-(3-Nitrophenyl)-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4h)
1
Yield 86 %, m.p. 245-247 °C. H NMR (400 MHz, DMSO-d6) d: 2.64 (d, J =
16.4 Hz, 1H, CH2), 3.24 (dd, J = 16.0, 7.2 Hz, 1H, CH2), 5.28 (d, J = 4.40 Hz,
1H, CH), 7.31–7.58 (m, 5H, ArH), 7.85–8.06 (m, 5H, ArH), 10.53 (s, 1H, NH). IR
(KBr) m: 3195, 3088, 2930, 1689, 1627, 1529, 1473, 1383, 1348, 1242, 1198, 1094,
1032, 976, 914, 864, 822, 798,777, 745, 695, 612, 584, 509, 426 cm-1
.
1-(4-Nitrophenyl)-1,2-dihydrobenzo[f]quinolin-3(4H)-one (4i)
1
Yield 82 %, m.p. 256–257 °C. H NMR (400 MHz, DMSO-d6) d: 2.6 (d, J =
16.4 Hz, 1H, CH2), 3.38 (dd, J = 16.4, 7.6 Hz, 1H, CH2), 5.46 (d, J = 5.2 Hz, 1H,
CH), 6.82 (d, J = 8.4 Hz, 2H, ArH), 7.12–7.31 (m, 4H, ArH), 7.36 (t, J = 7.6 Hz,
1H, ArH), 7.76 (d, J = 7.6 Hz, 1H, ArH), 7.92–8.09 (m, 2H, ArH), 10.62 (s, 1H,
NH). IR (KBr) m: 3203, 3067, 2941, 1680, 1626, 1524, 1474, 1391, 1348, 1317,
1237, 1161,973, 850, 818, 788, 748, 567, 432 cm-1
.
General synthetic procedure for compounds (6a–f)
A mixture of benzaldehyde 1 (2 mmol), naphthalene-2-amine (2 mmol), and
Meldrum’s acid 3 (2 mmol) in PEG-400 (2 g) was stirred for 7 h at 70 °C. The
progress of the reaction was monitored by TLC. After completion of the reaction, the
123

One-pot synthesis of benzoquinoline and coumarin derivatives
reaction mixture was filtered and the precipitate washed with water. The crude
products were purified by recrystallization from ethanol (95 %) to give products 6a–f.
4-(4-Chlorophenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin (6a)
1
Yield 81 %, m.p. 160–162 °C. H NMR (400 MHz, CDCl3) d: 1.07 (s, 3H, CH3),
1.09 (s, 3H, CH3), 2.31 (s, 2H, CH2), 2.47 (s, 2H,COCH2), 2.83–2.91 (m, 2H,
OCOCH2), 4.22–4.24 (m, 1H, CH), 7.01 (d, J = 8.0 Hz, 2H, ArH). IR (KBr) m:
1776, 1658, cm-1
.
4-(4-Benzyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin (6b)
1
Yield 75 %, m.p. 107–109 °C. H NMR (400 MHz, CDCl3) d: 1.08 (s, 3H, CH3),
1.12 (s, 3H, CH3), 2.26 (s, 2H, CH2), 2.29 (s, 3H, CH3), 2.50 (s, 2H,COCH2),
2.85–2.93 (m, 2H, OCOCH2), 4.22–4.25 (m, 1H, CH), 7.01 (d, J = 8.0 Hz, 2H,
ArH), 7.06 (d, J = 8.0 Hz, ArH). IR (KBr) m: 1789, 1680, cm-1
.
4-(4-Nitrophenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin (6c)
1
Yield 83 %, m.p. 132–134 °C. H NMR (400 MHz, CDCl3) d: 1.07 (s, 3H, CH3),
1.14 (s, 3H, CH3), 2.54 (s, 2H,COCH2), 2.89–3.03 (m, 2H, OCOCH2), 4.37–4.39
(m, 1H, CH), 7.32 (d, J = 8.0 Hz, 2H, ArH), 8.14 (d, J = 8.0 Hz, 2H, ArH). IR
(KBr) m: 1789, 1655, cm-1
.
4-(3-Methoxy-4-hydroxyphenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-
hexahydrocoumarin (6d)
1
Yield 72 %, m.p. 178–180 °C. H NMR (400 MHz, CDCl3) d: 1.12 (s, 3H, CH3),
1.17 (s, 3H, CH3), 2.35 (s, 2H, CH2), 2.55 (s, 2H,COCH2), 2.92–2.95 (m, 2H,
OCOCH2), 3.88 (s, 3H, OCH3), 4.24–4.26 (m, 1H, CH),6.61–6.85 (m, 3H, ArH),
10.92 (s, 1H, OH). IR (KBr) m: 1788, 1650, cm-1
.
4-(4-Methoxyphenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin (6e)
1
Yield 70 %, m.p. 129–131 °C. H NMR (400 MHz, CDCl3) d: 1.11 (s, 3H, CH3),
1.15 (s, 3H, CH3), 2.32 (s, 2H, CH2), 2.53 (s, 2H,COCH2), 2.90–2.92 (m, 2H,
OCOCH2), 3.77 (s, 3H, OCH3), 4.25–4.27 (m, 1H, CH),6.68–7.06 (m, 4H, ArH),
10.92 (s, 1H, OH). IR (KBr) m: 1771, 1650, cm-1
.
4-(4-(Dimethylamino)phenyl)-7,7-dimethyl-5-oxo-3,4,5,6,7,8-hexahydrocoumarin
(6f)
1
Yield 68 %, m.p. 182–184 °C. H NMR (400 MHz, CDCl3) d: 0.91 (s, 3H, CH3),
1.12 (s, 3H, CH3), 2.10 (s, 2H, CH2), 2.38 (s, 2H,COCH2), 2.64 (m, 2H, OCOCH2),
2.91 (s, 6H, 2NCH3), 4.06-4.34 (m, 1H, CH),6.50–7.15 (m, 4H, ArH), 10.92 (s, 1H,
OH). IR (KBr) m: 1791, 1703, cm-1
.
123

X. Wang et al.
In conclusion, two types of compound have been synthesized by use of a three-
component one-step reaction in the green medium PEG-400. All reagents were
obtained commercially and used without further purification. Melting points were
determined on an XT-4 electrothermal micromelting point apparatus and are
uncorrected. IR spectra were recorded using KBr pellets on a Digilab Merlin FT-IR
spectrophotometer. NMR spectra were recorded at 400 (1H) and 100 (13C) MHz,
respectively, on a Varian Mercury plus-400 instrument using CDCl3 as solvent and
TMS as an internal standard. Elemental analysis was performed on a Carlo-Erba
1106 elemental analysis instrument. Mass spectra were recorded on a Trace DSQ
instrument. Results were consistent with literature data.
Compared with the traditional two-step method, this method has the advantages
of milder reaction conditions, good yields, and easy processing; the method is also
environmentally benign. Reactions promoted by PEG-400 have attracted the
attention of organic chemists because of its solvating properties and its ability to act
as a phase-transfer catalyst. It also has negligible vapor pressure, is readily
recyclable, work up is easy, and it is eco-friendly and economical. Compared with
the reaction in organic solvent or in water with a catalyst, PEG-400 is more
environmentally friendly. PEG-400 is not only the reaction solvent but also the
phase-transfer catalyst, and is even recyclable. It also compares well with use of
ionic liquids, which are expensive and their lack of toxicity has not been confirmed.
We wish to report a simple but effective synthesis of benzo[f]quinolin derivatives
and hexahydrocoumarin derivatives using PEG-400 as reaction medium.
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