Practical and efficient synthesis of tetrahydrobenzo[b]pyran using caffeine supported on silica as an ionic liquid solid acid catalyst

Article abstract of DOI:10.1007/s13738-018-1468-y

The new catalyst silica-caffeine hydrogen sulfate [SiO₂-caff.]HSO₄ was conveniently prepared from commercially available 3-chloropropyltriethoxysilane via immobilization on silica followed by reaction with caffeine. The catalyst prepared was then characterized by the FT-IR spectroscopy, TGA, EDX, and SEM techniques. It was found that this heterogeneous catalyst was a highly efficient one for the synthesis of tetrahydrobenzo[b]pyrans in good-to-high yields, and could be recovered by a simple filtration of the reaction solution and reused for five consecutive runs. The attractive features of this method are simple procedure, clean reaction, easy work-up, use of a reusable catalyst, and performing a multi-component reaction.

Full text of DOI:10.1007/s13738-018-1468-y

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-018-1468-y
ORIGINAL PAPER
Practical and efficient synthesis of tetrahydrobenzo[b]pyran using
caffeine supported on silica as an ionic liquid solid acid catalyst
Mohammad Bakherad1 · Ali Keivanloo1 · Elmira Moradian1 · Amir H. Amin1 · Rahele Doosti1 · Mahsa Armaghan2
Received: 22 September 2017 / Accepted: 7 August 2018
© Iranian Chemical Society 2018
Abstract
The new catalyst silica-caffeine hydrogen sulfate [SiO2-caff.]HSO4 was conveniently prepared from commercially available
3-chloropropyltriethoxysilane via immobilization on silica followed by reaction with caffeine. The catalyst prepared was
then characterized by the FT-IR spectroscopy, TGA, EDX, and SEM techniques. It was found that this heterogeneous cata-
lyst was a highly efficient one for the synthesis of tetrahydrobenzo[b]pyrans in good-to-high yields, and could be recovered
by a simple filtration of the reaction solution and reused for five consecutive runs. The attractive features of this method
are simple procedure, clean reaction, easy work-up, use of a reusable catalyst, and performing a multi-component reaction.
Keywords Ionic liquid solid acid · Reusable catalyst · Tetrahydrobenzo[b]pyran
Introduction
in handling the separation procedures. On the basis of the
economic criteria, it is appealing to decrease the amount of
IL used in a potential process. Immobilized acidic ILs have
been utilized as novel solid catalysts for many acid-catalyzed
reactions such as nitration reaction, esterification, and acetal
formation [14, 15].
In the recent years, ionic liquids (ILs) have gained substan-
tial attention as eco-friendly reagents, catalysts, and solvents
in green synthesis due to their exclusive properties such as
non-flammability, low volatility, negligible vapor pressure,
high thermal stability, and ability to dissolve a broad range
of materials [1–6]. Among different ILs, the Brønsted acidic
ILs [7–9] are efficient, environmentally friendly, and sim-
ple acid catalysts that have been used in different organic
transformations [10–12]. Chemical industries, however, still
prefer to use heterogeneous catalysts, owing to their easy
separation and efficiency compared to the homogenous ILs
[13].
The generation of new methodologies for the production
of tetrahydrobenzo[b]pyran moiety is a topic of uninter-
rupted attention to synthetic/medicinal chemists since their
derivatives have versatile medicinal and biological properties
[16–18], and are broadly available in different biologically
active natural products [19]. Some heterogeneous catalysts
such as silica nanoparticles [20], poly(dimethylaminoethyl
acrylamide)-coated magnetic nanoparticles [21], and
Bi2WO6 nanoparticles [22] have been used for the synthesis
of tetrahydrobenzo[b]pyrans.
Recently, the immobilization process involving acidic
ILs on solid supports has been suggested. The heterogeni-
zation of reagents and catalysts can offer significant benefits
The use of bio-available, cheap, and non-toxic sources of
compounds is highly desirable for the design of any green
synthesis or process. Caffeine (1,3,7-trimethylpurine-2,6-di-
one) is a heterocyclic compound that has been classified by
the Food and Drug Administration as “safe”. It consists of a
pyrimidine ring fused to an imidazole ring having the chemi-
cal formula C8H10N4O2 [23]. Due to its unusual properties
such as inexpensive price, non-toxicity, stability in moisture
and air, and non-corrosive nature, caffeine has encouraged
increasing research interests as an effective and important
catalyst in organic synthesis [24]. We have recently reported
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s13738-018-1468-y) contains
supplementary material, which is available to authorized users.
* Mohammad Bakherad
m.bakherad@yahoo.com
1
School of Chemistry, Shahrood University of Technology,
Shahrood 3619995161, Iran
2
Chemistry Department, Science and Research Branch,
Islamic Azad University, Tehran, Iran
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
the synthesis of pyrazolopyranopyrimidines using caffeine
supported on boehmite nanoparticles [25].
points and 1H NMR data with those in the authentic samples.
The 1H NMR (300 MHz) and 13C NMR (75 MHz) spectros-
copies were run on a Bruker Advance DPX-250 FT-NMR
spectrometer. The chemical shift values were given as δ val-
ues against tetramethylsilane as the internal standard, and
the J values were given in Hz. Microanalysis was performed
on a Perkin-Elmer 240-B microanalyzer. Scanning electron
microscopy (SEM) studies were conducted on a VEGA
TESCAN instrument. Thermogravimetric analysis (TGA)
curves were recorded using a BAHR STA 503.
A solvent-free multi-component reaction is an eco-
friendly approach that has opened-up several likelihoods for
conducting fast organic synthesis and functional group trans-
formations [26, 27]. The purpose of this protocol was to give
prominence to the synergistic influences of the combined
usage of multi-component coupling reactions in solvent-free
conditions and application of a solid Brønsted acid catalyst
supported on silica for the generation of a new scheme for
heterocyclic synthesis. Thus, we investigated a straightfor-
ward one-pot synthesis of tetrahydrobenzo[b]pyran deriva-
tives using caffeine supported on silica [SiO2-caff.]HSO4
as an efficient, eco-environment, recyclable, and non-toxic
solid acid catalyst under solvent-free conditions (Scheme 1).
Preparation of SiO2‑3‑propyl‑imidazolopyridinium
hydrogen sulfate [SiO2‑Caff.]HSO4
Preparation of SiO2–Cl
For the preparation of the functionalized SiO2, silica (1.0 g)
was stirred in 100 mL of 1.0 M NaOH at room temperature.
Sodium silicate was filtered to remove undissolved particles.
Then, 3-(chloropropyl)trimethoxysilane (2.0 mL) was added
to the sodium silicate solution. The solution was titrated with
nitric acid (3.0 M), and titration was continued until the pH
of the solution reached 3.0. The white gel obtained was
separated by centrifugation, washed six times with distilled
water and acetone, and dried at room temperature to afforded
Experimental
The reagents and solvents used were supplied from Merck,
Fluka or Aldrich. Melting points were determined using an
electro-thermal C14500 apparatus. The reaction progress
and the purity of compounds were monitored using TLC
analytical silica gel plates (Merck 60 F250). All the known
compounds were identified by comparing their melting
OCH3
H3CO Si
OCH3
Cl
OH
OH
O-
O-
O
OH
RT
NaOH
O
Si
OH
Cl
OH
OH
O-
O-
(60 min)
HNO3 /RT
pH= 3/ (75min)
OH
O-
OH
OH
sodium silicate
SiO2
SiO2-Cl
OH
O
Cl
N
HSO4
OH
O
Caffeine, Acetone
reflux, 48h
Dry CH2Cl2
O
Si
OH
CH3
N
O
Si
OH
N
OH
CH3
N
H2SO4 (97%)
48h / Reflux
OH
OH
H3C
N
OH
H3C
N
O
O
N
N
CH3
O
CH3
O
[SiO2-Caff.]Cl
[SiO2-Caff.]HSO4
O
O
R2
R3
[SiO2-caff] HSO4
R3
R2CHO
+
+
solvent-free, 100 oC
R1
CN
R1
O
O
NH2
R1
R1
1
2
3
4
Scheme 1 Preparation of [SiO2-caff.]HSO4 and synthesis of tetrahydrobenzo[b]pyrans catalyzed by [SiO2-caff.]HSO4
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Journal of the Iranian Chemical Society
SiO2–Cl as a with powder [28]. Elementary analysis showed
that the carbon content of SiO2–Cl was 4.2%, which meant
that 0.86 mmol/g of pending groups were covalently bonded
to the surface of 1.00 g SiO2.
recrystallization from ethanol. To recover the catalyst, the
separated catalyst was washed twice with acetone (5 mL)
and reused after drying.
2‑amino‑3‑cyano‑4‑phe‑
Preparation of [SiO2‑Caff.]HSO4
nyl‑5‑oxo‑4H‑5,6,7,8‑tetrahydrobenzo[b]pyran (4a)
1
SiO2–Cl (1.00 g) was refluxed with caffeine (5.0 mmol,
0.04 g) in acetone (10.0 mL) for 36 h to replace the ter-
minal chlorine atoms. Caffeine-functionalized SiO2 [(SiO2-
Caff.)Cl] was filtered-off, washed three times with warm
acetone, and dried at 100 °C. Elementary analysis showed
the nitrogen content to be 1.0% (0.68 mmol/g), which meant
that 0.17 mmol of the pendant caffeine groups were cova-
lently bonded to the surface of SiO2–Cl (1.00 g), which
revealed that the caffeine loading near 20% of pending
chlorine atoms of SiO2–Cl, was changed to caffeine by
this reaction. In addition, the loading level of ion chlorides
was determined by potentiometric titration of the chlorine
content. For this purpose, 0.03 g of the sample was added
to 5.0 mL of deionized water and titrated by Ag+stand-
ard solution. The results showed that the loading level of
ion chlorides was 0.16 mmol/g. Then, into a three-necked
round-bottomed flask equipped with a stirrer, [SiO2-Caff]
Cl (1.0 g) was dispersed in dichloromethane (30 mL), and
sulfuric acid (98.99%) (0.1 g, 1 mmol) was added to this
suspension. The mixture was warmed up to the room tem-
perature and refluxed for 48 h. The [SiO2-Caff]HSO4 powder
obtained was filtered-off and washed with dichloromethane
(3 × 20 mL) and distilled water (3× 20 mL), respectively,
to remove additional acid, and then dried at 80 °C over-
night. Elementary analysis showed the sulfur content to be
0.14% (0.04 mmol/g). According to the sulfur content, the
number of H+ sites of [SiO2-caff]HSO4 was 0.04 mmol/g
(4×10−5 M), which meant that nearly 24% of pending ion
White solid; M.p., 211–213 °C; H NMR (300 MHz,
DMSO-d6): δ 1.95 (m, 2H, CH2), 2.25 (t, 2H, CH2), 2.62 (t,
2H, CH2), 4.18 (s, 1H, CH), 7.00 (s, 2H, NH2), 7.14–7.21
(m, 3H, H-Ar), 7.26–7.31 (m, 2H, H–Ar); IR ʋ (KBr): 3310,
3190, 2920, 2195, 1680, 1650, 1600, 1400, 1364, 1000/cm;
MS (EI), m/z [M]+ 266; Anal. Calcd. for C16H14N2O2: C,
72.16; H, 5.30; N, 10.52%. Found: C, 72.36; H, 5.22; N,
10.40%.
2‑amino‑3‑ethoxycarbonil‑4‑(4‑cyanophenyl)‑5‑oxo
‑4H‑5,6,7,8‑tetrahydrobenzo[b]pyran (4 h)
1
White solid; M.p., 187–190 °C; H NMR (300 MHz,
CDCl3): δ 1.016–1.063 (t, J=6.9 Hz, 3H, CH3), 1.80–2.01
(m, 2H, CH2), 2.24–2.29 (t, 2H, CH2), 2.48–2.53 (t, 2H,
CH2), 3.91–3.98 (q, 2H, CH2), 4.68 (s, 1H, CH), 6.19 (s,
2H, NH2), 7.30–7.33 (d, J=8.1 Hz, 2H, H–Ar), 7.42–7.45
(d, J=8.4 Hz, 2H, H–Ar); 13C NMR (75 MHz, CDCl3): δ
14.2, 20.1, 26.9, 34.4, 36.7, 59.8, 79.4, 109.8, 116.9, 119.2,
129.2, 131.7, 151.5, 158.3, 163.5, 168.6, 196.4; IR ʋ (KBr):
3400, 3200, 2860, 2229, 1685, 1660, 1595, 1484, 1439,
1375, 1240, 1015/cm; MS (EI), m/z [M]+ 338; Anal. Calcd.
for C19H18N2O4: C, 67.44; H, 5.36; N, 8.28%. Found: C,
67.25; H, 5.27; N, 8.10%.
2‑amino‑3‑ethoxycarbonil‑4‑(3‑hydroxy‑4‑methoxy
phenyl)‑5‑oxo‑4H‑5,6,7,8‑tetrahydrobenzo[b]pyran
(4i)
−
chloride (Cl−), was changed to hydrogen sulfate (HSO4 ) by
1
this reaction. This result obtained was confirmed by back-
titration analysis of the catalyst.
White solid; M.p., 187–190 °C; H NMR (300 MHz,
CDCl3): δ 1.17–1.22 (t, J=7.2 Hz, 3H, CH3), 1.93–2.07 (m,
2H, CH2), 2.32–2.38 (t, 2H, CH2), 2.52–2.59 (t, 2H, CH2),
3.83 (s, 3H, OCH3), 4.01–4.10 (q, 2H, CH2), 4.67 (s, 1H,
CH), 5.60 (s, 1H, OH), 6.19 (s, 2H, NH2), 6.70–6.72 (dd,
J=8.1 Hz, 1H, H-Ar), 6.79–6.80 (d, 1H, H–Ar), 6.84–6.88
(dd, J=8.4 Hz, 1H, H–Ar); IR ʋ (KBr): 3410, 3322, 2964,
1688, 1684, 1620, 1465, 1340, 1312/cm; MS (EI), m/z [M]+
359; Anal. Calcd. for C19H21NO6: C, 63.50; H, 5.89; N,
3.90%. Found: C, 63.29; H, 5.80; N, 3.75%.
General procedure for synthesis
of tetrahydrobenzo[b]pyran derivatives
(4a–4t)
To a mixture of 1,3-cyclohexanedione or 5,5- dimethyl-
1,3-cyclohexanedione (1.0 mmol), an aldehyde (1.0 mmol),
and malononitrile (1.0 mmol) in a test tube was added
[SiO2-Caff.]HSO4 (0.1 g, 0.09 mmol of H+), and the reac-
tion mixture was heated at 100 °C. After completion of the
reaction, monitored by thin-layer chromatography (TLC),
the precipitate formed was washed with warm ethanol
(3 × 30 mL) to separate the heterogeneous catalyst. The
pure tetrahydrobenzo[b]pyran product was obtained after
2‑amino‑3‑ethoxycarbonil‑4‑(2‑bromophenyl)‑5‑ox
o‑4H‑5,6,7,8‑tetrahydrobenzo[b]pyran (4j)
1
White solid; M.p., 200–203 °C; H NMR (300 MHz,
CDCl3): δ 1.12–1.16 (t, J = 6.9 Hz, 3H, CH3), 1.91–2.07
(m, 2H, CH2), 2.31–2.35 (t, J = 6.0 Hz, 2H, CH2),
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Journal of the Iranian Chemical Society
2.54–2.60 (t, 2H, CH2), 3.99–4.10 (q, 2H, CH2), 5.03 (s,
1H, CH), 6.29 (s, 2H, NH2), 6.95–7.00 (t, J = 8.1 Hz, 1H,
H–Ar), 7.16–7.21 (t, J = 7.2 Hz, 1H, H–Ar), 7.30–7.32
(d, J = 7.8 Hz, 1H, H–Ar), 7.43–7.46 (d, J = 6.9 Hz, 1H,
H–Ar); 13C NMR (75 MHz, DMSO-d6): δ 14.7, 20.3,
26.9, 34.7, 36.9, 59.1, 77.2, 115.8, 123.6, 127.5, 128.0,
132.4, 132.9, 145.1, 159.5, 164.4, 168.6, 196.1; IR ʋ
(KBr): 3400, 3200, 2860, 1685, 1660, 1595, 1484, 1439,
1375, 1240, 1015, 590/cm; MS (EI), m/z [M]+ 391; Anal.
Calcd. for C18H18BrNO4: C, 55.12; H, 4.63; N, 3.57%.
Found: C, 55.30; H, 4.56; N, 3.40%.
2‑amino‑3‑ethoxycar‑
bonil‑4‑(2,6‑dichlorophenyl)‑7,7‑dime‑
thyl‑5‑oxo‑4H‑5,6,7,8‑tetrahydrobenzo[b]pyran (4r)
White solid; M.p., 241–243 °C; 1H NMR (300 MHz, CDCl3):
δ 0.721 (s, 3H, CH3), 0.826 (s, 3H, CH3), 0.916–0.958 (t,
J = 7.2 Hz, 3H, CH3), 2.32–2.37 (t, J= 6.3 Hz, 2H, CH2),
2.52–2.57 (t, 2H, CH2), 4.00–4.07 (q, 2H, CH2), 5.54 (s, 1H,
CH), 6.35 (s, 2H, NH2), 6.98–7.04 (t, J=7.8 Hz, 1H, H–Ar),
7.15 (d, 1H, H–Ar), 7.33 (d, 1H, H–Ar); 13C NMR (75 MHz,
DMSO-d6): δ 11.2, 11.5, 14.4, 20.3, 26.9, 31.6, 37.0, 59.0,
74.2, 112.9, 128.2, 128.5, 130.1, 134.4, 138.2, 138.7, 160.2,
165.2, 168.6, 196.2; IR ʋ (KBr): 3424, 3312, 2944, 1686,
1644, 1616, 1460, 1450, 1380, 1300, 1000, 769 /cm; MS
(EI), m/z [M]+ 409; Anal. Calcd. for C20H21Cl2NO4: C,
58.55; H, 5.16; N, 3.41%. Found: C, 58.38; H, 5.08; N,
3.27%.
2‑amino‑3‑ethoxycarbonil‑4‑(3‑hyd
roxy‑4‑methoxyphenyl)‑7,7‑dime‑
thyl‑5‑oxo‑4H‑5,6,7,8‑tetrahydrobenzo[b]pyran (4q)
1
White solid; M.p., 180–183 °C; H NMR (300 MHz,
It was also crystallized from ethanol in the form of white
needles, and was characterized by single-crystal X-ray crys-
tallography. This analysis showed that it was crystallized in
the triclinic system with space group P-1, and there were
also two molecules present in each unit cell. Figure 1 shows
a perspective view of the molecular structure of 4r.
CDCl3): δ 1.00 (s,3H, CH3), 1.10 (s,3H, CH3), 1.18–1.23
(t, J = 7.2 Hz, 3H, CH3), 2.15–2.27 (dd, J = 16.2 Hz, 2H,
CH2), 2.42 (dd, 2H, CH2), 3.82 (s, 3H, OCH3), 4.01–4.12
(q, 2H, CH2), 4.64 (s, 1H, CH), 5.62 (s, 1H, OH), 6.19
(s, 2H, NH2), 6.69–6.72 (dd, J = 8.1 Hz, 1H, H–Ar),
6.79–6.80 (dd, 1H, H–Ar), 6.81–6.85 (dd, J = 8.1 Hz,
1H, H-Ar); 13C NMR (75 MHz, CDCl3): δ 14.2, 27.6,
29.0, 32.2, 33.1, 40.6, 50.7, 55.8, 59.6, 80.8, 109.9, 114.1,
116.8, 120.1, 139.2, 144.8, 145.0, 158.3, 161.3, 169.1,
196.5; IR ʋ (KBr): 3400, 3300, 3186, 2933, 1675, 1643,
1590, 1460, 1360, 1000 /cm; MS (EI), m/z [M]+ 387;
Anal. Calcd. for C21H25NO6: C, 65.10; H, 6.50; N, 3.62%.
Found: C, 64.90; H, 6.58; N, 3.48%.
Results and discussion
Catalyst preparation
Silica-caffeine hydrogen sulfate ([SiO2-caff]HSO4) was syn-
thesized as shown in Scheme 1, wherein the first step was the
synthesis of silica-bonded n-propyl chloride according to an
Fig. 1 ORTEP representation
of 4r. Displacment ellipsoids
are drawn at 50% probability
level, and H atoms are shown
as small spheres of arbitrary
radii. CCDC 1552689 contains
supplementray crystallographic
data for this article
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Journal of the Iranian Chemical Society
earlier report [28]. The second step was the pending chlorine
atoms of SiO2–Cl changing to imidazolopyridinium chloride
by refluxing with caffeine in acetone to afford [SiO2-caff]
Cl. Finally, [SiO2-caff]Cl and sulphuric acid were refluxed
in dichloromethane to generate [SiO2-caff]HSO4. The cata-
lyst produced was characterized by the FT-IR spectroscopy,
TGA, DTA, SEM, and EDX techniques.
(Fig. 2b). Attachment of caffeine onto the SiO2-bonded
n-propyl chloride was confirmed by the appearance of
new bands at 1704 and 1650/cm due to the C=O and C=N
stretching vibrations, respectively.
EDX analysis also confirmed the presence of sulfur atoms
on the surface of [SiO2-caff.]HSO4 in addition to the carbon,
oxygen, nitrogen, chlorine, and silicon atoms (Fig. 3).
Figure 4 shows the TG/DTG thermogram of the
[SiO2-caff.]HSO4 catalyst. There was an important weight
loss region in the TG curve in the temperature range of
295–500 °C, accompanied by an endothermic peak in the
DTG curve, which could be related to the decomposition of
the organic residue on the surface of SiO2.
Catalyst characterization
The FT-IR spectra for SiO2 (a), SiO2-bonded n-propyl chlo-
ride ([SiO2–Cl]) (b), and silica-caffeine hydrogen sulfate
([SiO2-caff]HSO4) (c) are shown in Fig. 2. A broad band
was observed in the range of 3413–3321/cm in all samples,
assigned to the O–H stretching vibration. In addition, the
characteristic bands for SiO2 were observed in 1168, 810,
and 478/cm, which were assigned to the stretching and
bending vibrations of its Si–O–Si (Fig. 2a). Moreover, the
band at 2950/cm for the SiO2-bonded n-propyl chloride
was assigned to the streching vibration of the C–H bonds
The morphology of the SiO2 and [SiO2-caff.]HSO4 sam-
ples were also investigated by SEM in Fig. 5. The compari-
son between their SEM images showed that the reaction pro-
cedure for the preparation of the [SiO2-caff.]HSO4 samples
from SiO2 changed the morphology of the particles.
Catalytic activity
To test the catalytic activity of [SiO2-caff.]HSO4 in the syn-
thesis of tetrahydrobenzo[b]pyrans, the reaction between
benzaldehyde, malononitrile, and 1,3-cyclohexanedione was
selected as a model reaction to optimize the reaction condi-
tions, and the results obtained were tabulated in Table 1. The
influence of different parameters was examined to obtain
the best possible combination. The parameters included the
solvent, reaction temperature, and catalyst concentration. As
shown in Table 1, several solvents were screened for the
reaction in the presence of a catalytic amount of [SiO2-caff.]
HSO4. The results obtained showed that the efficiency and
yield of the reaction under solvent-free conditions at 100 °C
were higher than those obtained in solvents such as H2O,
EtOH, CH3CN, DMF, and toluene (Table 1, entries 1–6).
c
95
1650.95
1704.95
2954.73
75
55
35
15
-5
1550.65
b
a
2950.87
810.04
478.31
900 400
1168.78
1900
3400
2900
2400
1400
Fig. 2 FT-IR spectra for SiO2 (a), [SiO2–Cl] (b), and [SiO2-caff]
HSO4 (c)
Fig. 3 EDX analysis of
[SiO2-caff.]HSO4
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Journal of the Iranian Chemical Society
Fig. 4 TGA and DTA diagrams
for [SiO2-caff.]HSO4 catalyst
Fig. 5 SEM of SiO2 (a) and [SiO2-Caff.]HSO4 (b)
Decreasing the loading of the catalyst to 0.4 mol% low-
ered the reaction yield dramatically (Table 1, entry 7). How-
ever, increasing the amount of catalyst to 2 mol% showed
no substantial improvement in the yield (Table 1, entry 9).
Furthermore, the effect of temperature on the conversion
was checked, and the results obtained were tabulated in
Table 1. It is obvious that at 80 °C, a low reaction yield was
formed (Table 1, entry 10). Increasing the temperature did
not improve the reaction yield (Table 1, entry 11). In addi-
tion, when the reaction was carried out in the absence of a
catalyst, only a low reaction yield was obtained, even after
the reaction time was prolonged to 6 h (Table 1, entry 12).
To find out the roles of [SiO2-Caff.]Cl and [SiO2-caff.]HSO4
during the reactions, the synthesis of of tetrahydrobenzo[b]
pyran 4a was examined in the presence of [SiO2-Caff.]Cl. As
shown in Table 1, the products were obtained in 30% yield
in the presence of SiO2 (Table 1, entry 13).
Under the optimized reaction conditions, the general-
ity of this three-component reaction was studied under the
optimal reaction conditions by varying the structures of the
aldehydes involved. The results obtained are summarized
in Table 2.
As shown in this table, the variation in the electronic
properties and the position of the functional groups on
the aromatic ring of the aldehyde did not show a clear
effect on the reaction yields. For example, aldehydes with
electron-donating groups (Table 2, entries 2, 6, 9, 11, 13,
16, and 17) or electron-withdrawing groups (entries 3, 7,
8, 14, 19, and 20) were condensed into the corresponding
tetrahydrobenzo[b]pyrans in high yields. Moreover, the
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Journal of the Iranian Chemical Society
Table 1 Optimization of
reaction conditions for synthesis
of 4a
Entry
Solvent
Catalyst (mol%)
Temp. (°C)
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
H2O
EtOH
CH3CN
DMF
0.7
0.7
0.7
0.7
0.7
0.7
0.4
1
2
0.7
0.7
Reflux
Reflux
Reflux
80
100
100
100
100
100
80
120
100
100
90
150
240
120
360
20
60
20
15
40
81
76
63
75
49
90
45
90
91
75
91
10
30
Toluene
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
20
360
60
No catalyst
[SiO2-caff.]Cl
Bold condition indicate better result than other conditions
Reaction conditions: benzaldehyde (1.0 mmol), malononitrile (1.0 mmol), 1,3-cyclohexanedione
(1.0 mmol), catalyst, solvent (3 mL)
aIsolated yield
Table 2 Synthesis of
Entry R1
R2
R3
Product Reaction Yield (%)a M.p. (°C) (Lit.) [ref.]
time (min)
tetrahydrobenzo[b]pyrans
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
C6H5
CN
CN
CN
CO2Et 4d
CO2Et 4e
CO2Et 4f
CO2Et 4g
CO2Et 4h
4a
4b
4c
20
35
10
25
20
35
10
20
25
40
30
15
20
10
30
35
30
30
20
15
90
86
95
90
94
87
90
96
94
89
89
90
87
95
80
84
92
90
85
93
211–213 (213–15) [29]
196–197 (198–200) [30]
236–238 (234–236) [31]
185–187 (188–190) [31]
179–181 (183–184) [32]
170–171 (168–169) [33]
180–182 (179–181) [31]
189–191
4–MeO–C6H4
4–NO2–C6H4
C6H5
4–Cl–C6H4
4–Me–C6H4
4–NO2–C6H4
4–CN-C6H4
9
3–OH–4–OMe–C6H3 CO2Et 4i
2–Br–C6H4 CO2Et 4j
187–190
200–203
10
11
12
13
14
15
16
17
18
19
20
CH3 4–Me–C6H4
CH3 4–Cl–C6H4
CH3 3–OH–4–OMe–C6H3 CN
CH3 4–NO2–C6H4
CH3 C6H5
CH3 4–MeO–C6H4
CN
CN
4k
4l
4m
4n
208–210 (210–213) [30]
212–214(213–215) [29]
237–240 (238–240) [31]
181–184 (184–185) [31]
145–147 (144–146) [32]
135–137 (131–134) [32]
180–183
241–243
152–155 (154–156) [32]
178–180 (179–181) [31]
CN
CO2Et 4o
CO2Et 4p
CH3 3–OH–4–OMe–C6H3 CO2Et 4q
CH3 2,6–Cl2C6H3
CH3 3–NO2–C6H4
CH3 4–NO2–C6H4
CO2Et 4r
CO2Et 4s
CO2Et 4t
Reaction conditions: aldehyde (1.0 mmol), malononitrile or ethylcyanoacetate (1.0 mmol), 1,3-cyclohexan-
edione or 5,5-dimethyl-1,3-cyclohexanedione (1.0 mmol), catalyst (0.7 mol%), solvent free, 100 °C
aIsolated yield
steric effects of the substituents at the ortho-position of the
aldehydes did not have a clear effect on the reaction yields
(Table 2, entries 10 and 18).
We also investigated the recyclability of [SiO2-caff.]
HSO4 using the reaction of benzaldehyde, malononitrile,
and 1,3-cyclohexanedione at 100 °C under solvent-free
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Journal of the Iranian Chemical Society
Scheme 2 Proposed mechanism
[SiO -Caff]
SO4
H
2
H
O
O
H
O
O
(II)
(I)
[SiO2-Caff]
SO4
H
H
CN
CN
OH
H
Ph
H
CN
CN
H
3
O
-H2O
Ph
NC
Ph
H
CN
H
(III)
2a
H
SO
4
[SiO2-Caff]
[SiO -Caff]
SO4
2
O
Ph
O
O
Ph
O
Ph
H
H
CN
CN
NH
CN
NH2
O
O
N
4a
9
H
H
[SiO2-Caff] SO4
SO
4
[SiO2-Caff]
conditions. The catalyst was recovered by a simple filtra-
tion and reused over five runs without significant losses in
the catalytic activity.
times without a significant loss in its catalytic activity.
Moreover, the catalyst was characterized by various meth-
ods including TGA, SEM, EDX, and FT-IR spectroscopy.
A proposed mechanism for the synthesis of
tetrahydrobenzo[b]pyran 4a from benzaldehyde, malon-
onitrile, and 1,3-cyclohexandion catalyzed by [SiO2-Caff.]
HSO4 is shown in Scheme 2. 1,3-cyclohexanedione was
converted to its corresponding enolate form (II) in the
presence of [BNPs-caff.]HSO4. The acidic catalyst played
a major role in its promoting activity for the formation of
phenylidenemalononitrile III, which was readily prepared
in situ by the Knoevenagel condensation of benzaldehyde 2a
with the highly active CH acidic malononitrile 3. Finally, the
Michael-type addition of the enolate form II to phenyliden-
emalononitrile III followed by cyclization and tautomeriza-
tion yielded tetrahydrobenzo[b]pyran 4a (Scheme 2).
Acknowledgements We gratefully acknowledge the financial support
of the Research Council of the Shahrood University of Technology.
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