Fructose-catalyzed synthesis of tetrahydrobenzo[b]pyran derivatives: Investigation of kinetics and mechanism

Article abstract of DOI:10.1016/S1872-2067(14)60302-8

Fructose was used as an efficient catalyst for three-component condensation reactions of aryl aldehydes, malononitrile, and dimedone in a mixture of EtOH and H₂O as green solvents. The advantages of this method are a short reaction time, high y

Full text of DOI:10.1016/S1872-2067(14)60302-8

Chinese Journal of Catalysis 36 (2015) 757–763
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article
Fructose-catalyzed synthesis of tetrahydrobenzo[b]pyran
derivatives: Investigation of kinetics and mechanism
Sayyedeh Shadfar Pourpanah, Sayyed Mostafa Habibi-Khorassani *, Mehdi Shahraki
Department of Chemistry, University of Sistan and Baluchestan, Zahedan, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
Fructose was used as an efficient catalyst for three-component condensation reactions of aryl alde-
Received 16 December 2014
Accepted 19 January 2015
Published 20 May 2015
hydes, malononitrile, and dimedone in a mixture of EtOH and H O as green solvents. The advantages
of this method are a short reaction time, high yields, low cost, easy accesses, and simple work-up.
The mechanism of the synthesis of a derivative of 4H-tetrahydrobenzo[b]pyran was clarified using
2
spectroscopic kinetic methods. The activation energy (E
rameters (ΔG = 69.14 kJ/mol, ΔS = 20.99 J/(mol·K), and ΔH = 62.89 kJ/mol) were calculated,
a
= 65.34 kJ/mol) and related kinetic pa-
‡
‡
‡
Keywords:
Fructose
Catalyst
Kinetics
Mechanism
Tetrahydrobenzo[b]pyran derivative
based on the effects of temperature, concentration, and solvent. The first step in the proposed
mechanism was identified as the rate-determining step (k ), based on the steady-state approxima-
1
tion.
©
2015, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
1.
Introduction
nium hydroxide [12], diammonium hydrogen phosphate [13],
fluoride ions [14], magnesium oxide [15], sodium selenite [16],
Tetrahydrobenzo[b]pyran derivatives are important in drug
iodine [17], H
mide [19], cerium(III) chloride [20], lithium bromide [21],
RE(PFO) (RE: rare earth) [22], Amberlite IRA-40 (OH) [23],
acidic ionic liquids [24], l-proline [25], ZnO–β-zeolite [26],
trisodium citrate [27], and basic ionic liquids [28]. Most of
these synthetic methods suffer from drawbacks such as the use
of toxic catalysts, strong basic conditions, expensive and com-
plex catalysts or reagents, many tedious steps, and, in most
cases, low product yields and long reaction time; these restrict
use of these derivatives in practical application.
6
P
2
W
12
O
62·H
2
O [18], tetrabutylammonium bro-
research because of their various biological and pharmacologi-
cal activities such as spasmolytic, diuretic, anticoagulant, anti-
cancer, antianaphylactic, antioxidant, antileishmanial, antibac-
terial, antifungal, hypotensive, antiviral, antiallergenic, and
antitumor activities [1–6]. They can also be used as cognitive
enhancers for the treatment of neurodegenerative diseases,
including Alzheimer’s disease, amyotrophic lateral sclerosis,
Huntington’s disease, Parkinson’s disease, AIDS-associated
dementia, and Down’s syndrome, and for the treatment of
schizophrenia and myoclonus [7]. Some 4H-benzo[b]pyran
derivatives are useful as photoactive materials [8]. Conse-
quently, many methods for the synthesis of these compounds
have been reported, including the use of microwave [9] and
ultrasonic irradiations [10], sodium bromide [10], hexadecyl-
dimethylbenzylammonium bromide [11], tetramethylammo-
3
Recently, organic reactions in green solvents such as H
2
O,
EtOH, and H O-EtOH mixture have attracted much attention,
2
because they are cheap, safe, and environmentally benign
[29,30]. They also avoid the use of harmful organic solvents. In
a continuation of our research on using cheap, easily accessible,
biodegradable, green catalysts and solvents [31–34], we de-
*
Corresponding author. Tel/Fax: +98-541-2446565; E-mail: smhabibi@chem.usb.ac.ir
This work was supported by the Research Council of the University of Sistan and Baluchestan.
DOI: 10.1016/S1872-2067(14)60302-8 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 36, No. 5, May 2015

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Sayyedeh Shadfar Pourpanah et al. / Chinese Journal of Catalysis 36 (2015) 757–763
veloped new synthetic methods for the preparation of tetrahy-
drobenzo[b]pyran derivatives using aryl aldehydes (1), malo-
nonitrile (2), and dimedone (3) in the presence of fructose as a
complete, the mixture was cooled to room temperature and the
products were isolated by filtration, washed with H O, and
recrystallized from EtOH (95%) to afford pure products.
Selected spectroscopic data of some products are given be-
low.
2-Amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-4-phenyl-4H-
2
2
catalyst in H O-EtOH at 40 °C (Fig. 1). This is a one-pot,
2
three-component reaction in EtOH-H O; it is operationally sim-
ple, clean, and efficient, and consistently gives the correspond-
ing products in good to excellent yields. In recent years, we
have tried to expand experimental and theoretical studies on
the kinetics and mechanisms of some organic reactions
−1
chromene-3-carbonitrile (Table 3, entry 1). IR (KBr, cm ):
3390, 3245, 2960, 2190, 1676, 1209; 1H NMR (400 MHz,
CDCl ): δ (ppm) = 1.07 (s, 3H), 1.14 (s, 3H), 2.25 (dd, J = 16.4 Hz,
3
[
35–38]. In this study, we used ultraviolet-visible (UV-Vis) and
2H,), 2.48, (s, 2H), 4.43 (s, 1H), 4.55 (s, 2H), 7.2, 7.3 (m, 5H).
2-Amino-5,6,7,8-tetrahydro-4-(2,3-dimethoxyphenyl)-7,7-
dimethyl-5-oxo-4H-chromene-3-carbonitrile (Table 3, entry 7).
1
dynamic H nuclear magnetic resonance (NMR) spectroscopies,
and theoretical calculations to elucidate the detailed kinetics
and mechanisms of these reactions. We report, for the first
time, kinetic results together with detailed mechanistic studies
of the synthesis of a derivative of 4H-tetrahydrobenzo[b]pyran,
based on a global kinetic analysis method using UV-Vis spec-
troscopy.
−1
1
IR (KBr, cm ): 3305, 3205, 2945, 2175, 1676, 1212; H NMR
(400 MHz, DMSO-d ): δ (ppm) = 1.08 (s, 3H), 1.12 (s, 3H), 2.22
6
(dd, J = 16 Hz, 2H), 2.44 (dd, J = 17.6, 2H), 3.85 (s, 3H), 3.95 (s,
3H), 4.52 (s, 2H), 4.74 (s, 1H), 6.716–6.809 (dd, J = 8, 2H), 6.972
(t, J = 8, 1H).
2
-Amino-5,6,7,8-tetrahydro-4-(4-methyl)-7,7-dimethyl-5-oxo-
−1
2
.
Experimental
.1. Chemicals and equipment
All reagents were purchased from Merck and Aldrich, and
4H-chromene-3-carbonitrile (Table 3, entry 11). IR (KBr, cm ):
465, 3320, 2955, 2190, 1676, 1247; 1H NMR (400 MHz,
DMSO-d ): δ (ppm) = 1.08 (s, 3H), 1.12 (s, 3H), 2.23 (dd, J = 16.4
3
2
6
Hz, 2H), 2.30 (s, 3H), 2.40 (dd, J = 17.6, 2H), 4.52 (s, 2H), 4.74(s,
1H), 6.716–6.809 (m, 2H), 6.972 (t, 1H).
used without purification. All yields refer to isolated products
after purification. The products were identified by comparison
of their physical data with those of authentic samples, and from
infrared (IR) and NMR spectroscopic data. NMR spectra were
recorded using a Bruker Avance DRX 400 MHz instrument. The
3. Results and discussion
3.1. Optimization of synthetic conditions
spectra were measured in DMSO-d
6
relative to tetrame-
We studied the reaction of benzaldehyde (1 mmol), malo-
nonitrile (1 mmol), and dimedone (1 mmol) to optimize the
reaction conditions. As the data in Tables 1 and 2 show, the
best results were obtained at 40 °C in the presence of 0.036 g
thylsilane (0.00 ppm). IR spectra were recorded using a JASCO
FT-IR 460Plus spectrophotometer. Melting points were deter-
mined in open capillaries, using an electrothermal 9100 melt-
ing-point apparatus. Thin-layer chromatography (TLC) was
performed on silica-gel Polygram SILG/UV 254 plates. Rate
constants are presented as averages of several kinetic runs (at
least 6–10) and are reproducible within ±3%. The overall reac-
tion was determined by monitoring the absorbance changes of
the products with time, using a Varian (Model Cary Bio-300)
UV-Vis spectrophotometer with a 10 mm light-path cell. The
reaction temperature was maintained to within ±0.1 °C at var-
ious temperatures, using a circulating water bath.
(20 mol%) fructose in H O-EtOH (2:1).
2
The scope and efficiency of the reaction under the optimum
conditions were explored for the synthesis of a wide variety of
substituted tetrahydrobenzo[b]pyran derivatives from aryl
aldehydes, malononitrile, and dimedone. The results are sum-
marized in Table 3.
Table 1
Effects of various solvents on synthesis of tetrahydrobenzo[b]pyran
derivatives in presence of fructose (20 mol%) at 40 °C.
Entry
Solvent
EtOH
Time (min)
Yield (%)
2
.2. General procedure for synthesis of
1
2
3
4
5
6
150
160
70
45
50
44
51
50
86
68
40
tetrahydrobenzo[b]pyran derivatives
H O
2
H
H
H
H
2
O-EtOH (3:1)
2
O-EtOH(2:1)
O-EtOH(1:1)
O-EtOH(2:1)
Fructose (20 mol%) was dissolved in H
O-EtOH (2:1) and an
2
2
aryl aldehyde (1 mmol), malononitrile (1 mmol), and dimedone
1 mmol) were added to the solution at 40 °C. The progress of
2
60
(
Table 2
the reaction was monitored by TLC. When the reaction was
Effect of amount of catalyst on synthesis of tetrahydrobenzo[b]pyran
R
derivatives at 40 °C.
Entry
Catalyst (mol%)
Yield (%)
CHO
O
O
O
1
2
3
4
5
6
5
10
15
20
25
30
58
73
70
86
75
73
Fructose (20 mol%)
O:EtOH (2:1)
CN
NH
CN
CN
+
+
R
H
2
O
2
1
2
3
0 o
4
C
Fig. 1. Synthesis of tetrahydrobenzo[b]pyran derivatives in presence of
fructose.

Sayyedeh Shadfar Pourpanah et al. / Chinese Journal of Catalysis 36 (2015) 757–763
759
Table 3
Synthesis of tetrahydrobenzo[b]pyran derivatives via condensation of aryl aldehydes (1), malononitrile (2), and dimedone (3) in the presence of
2
fructose (20 mol%) in H O-EtOH (2:1) at 40 °C.
Melting point (°C)
Observed
Entry
Aromatic aldehyde
CHO
Time (min)
Yield (%)
Reported
1
2
3
4
5
C H
6 5
45
80
85
75
60
165
60
15
10
10
86
78
72
67
36
76
71
87
85
89
89
60
227–228
208–209
206–208
118–120
193–195
218–220
217–219
217–219
208–210
176–178
208–211
218–220
226–228 [15]
207–209 [26]
208–210 [39]
115–117 [22]
196–198 [26]
210–212 [14]
216–218 [40]
220–222 [39]
212–214 [15]
177–178 [26]
214–216 [12]
222–224 [12]
4-ClC
2-ClC
6
H
H
4
CHO
CHO
6
4
2,4-(Cl)
4-(OMe)C
Thiophene-2-carbaldehyde
2,3-(OMe) CHO
2 6 3
C H CHO
6 4
H CHO
6
7
8
9
1
1
1
C H
2 6 3
2-NO
3-NO
4-NO
2 6 5
C H CHO
2 6 5
C H CHO
2 6 5
C H CHO
0
1
2
6 5
4-MeC H CHO
10
135
2-Furaldehyde
Various aryl aldehydes with electron-withdrawing or elec-
relationship between the absorbance and concentrations val-
ues.
The reaction kinetics was followed based on the UV ab-
sorbance measurements with respect to time at the same con-
tron-releasing substituents (ortho-, meta-, and pa-
ra-substituted) participated well in this reaction and gave the
products in good to excellent yields.
We propose the following mechanism for the synthesis of a
tetrahydrobenzo[b]pyran derivative in the presence of fructose
as a catalyst. First, Knoevenagel condensation between
catalyst
catalyst
Fructose
Fructose
O
H
H
NC
C CN
HO
4
2
-nitrobenzaldehyde (1) and malononitrile (2) produces
-benzylidenemalononitrile (I ). Michael addition of I with
H
C
O
C
k1
O
2
N
C
+
H
2
O
1
1
+
2
O N
N
N
k-1
2
dimedone (3), followed by cyclization and tautomerization,
affords the corresponding product 4 (Fig. 2).
1
I
1
catalyst
Fructose
NO
2
catalyst
Fructose
NO
2
O
HO
O
3.2. Kinetics
H
HO
k
2
+
CN
3
H C
C
O
3
H C
H
3
C
CH CN
CN
To gain an insight into the mechanism of tetrahydroben-
zo[b]pyran derivative synthesis, a kinetic study of the reaction
of 4-nitrobenzaldehyde (1), malononitrile (2), and dimedone
CN
O
3
H C
I
1
3
I
2
catalyst
Fructose
catalyst
Fructose
NO
2
NO
2
2
(3) in the presence of fructose in H O-EtOH (2:1) was per-
H
O
HO
OH
O
formed using UV-Vis spectroscopy. First, it was necessary to
find an appropriate wavelength for the kinetic study. A solution
k3
H
CH CN
CN
3
H C
3
H C
(10 mmol/L) of each reactant, i.e., 1, 2, and 3, and a fructose
CH CN
CN
O
3
H C
H
3
C
O
solution (25 mmol/L) were prepared in H O-EtOH (2:1). An
2
I3
I
2
aliquot (approximately 3 mL) of each reactant was pipetted
into a 10 mL light-path quartz spectrophotometer cell, and the
spectrum of each compound was recorded at 25 °C over the
wavelength range 200–600 nm. In the second experiment, ali-
quots (0.2 mL) of a solution (40 mmol/L) of fructose and of
reactants 1 and 3 were pipetted into a quartz spectrophotom-
eter cell and then an aliquot (0.8 mL) of a solution (4 mmol/L)
of reactant 2 was added to the mixture, according to the stoi-
chiometry of each reactant in the overall reaction. The reaction
was monitored by recording scans of the entire spectra at 20
min intervals during the reaction, at ambient temperature (Fig.
NO
2
NO2
H
O
k4
O
H
C
CN
CN
NH
CH
C
H
3
C
H C
C
O
3
O
H
3
C
N
3
H C
I
3
I4
NO
2
NO
2
O
O
H
C
C
k5
,3 H
CN
NH2
CN
NH
3). As Fig. 3 shows, the appropriate wavelength was 385 nm
3
H C
1
H
3
C
O
3
H C
(corresponding mainly to product 4). At this wavelength, reac-
O
3
H C
tants 1, 2, 3, and fructose have almost no absorbance, which
provides practical conditions for kinetic and mechanistic inves-
tigations of the reaction. In all the experiments, the UV-vis
spectrum of the product was measured over the product con-
centration range from 0.1 to 10 mmol/L to confirm the linear
I4
4
(product)
Fig. 2. Proposed mechanism of reaction of 1, 2, and 3 in the presence of
fructose for synthesis of 2-amino-5,6,7,8-tetrahydro-7,7-dimthyl-4-
(4-nitrophenyl)-5-oxo-4H-chromene-3-carbonitrile (4) in H O-EtOH
2
(2:1).

760
Sayyedeh Shadfar Pourpanah et al. / Chinese Journal of Catalysis 36 (2015) 757–763
3.0
2.5
2.0
1.5
1.0
0.5
1.30
1.25
1
.20
.15
1
0
5
10
15
20
Time (min)
Fig. 5. Pseudo-second-order fit curve (solid line) and original experi-
mental curve (dotted) for reaction of dimedone, malononitrile, and
3
80
400
420
Wavelength (nm)
4-nitrobenzaldehyde in the presence of fructose at 385 nm and 25.0 °C
Fig. 3. UV-Vis spectra of reaction of 4-nitrobenzaldehyde (1; 10
mmol/L), malononitrile (2; 10 mmol/L), and dimedone (3; 10 mmol/L)
in H O-EtOH (2:1).
2
in the presence of fructose (25 mmol/L) as a catalyst in H O-EtOH (2:1).
2
Here, the original experimental absorbance shows sec-
ond-order behavior as a function of time. This is shown by the
full line at 385 nm, which exactly fits the experimental results
centrations 10 mmol/L of 1, 2, and 3 in the presence of fructose
2.5 mmol/L) in H O-EtOH (2:1) at 25 °C (Fig. 4).
The infinity absorbance (A ) was obtained at 50 min, as
(
2
(Fig. 5). The rate constant (kobs) was obtained from the experi-
∞
mental curve.
shown in Fig. 4. A second-order fit curve (solid line) was ob-
tained from the absorbance data versus time at 385 nm, which
precisely described the experimental curve (dotted line), as
shown in Fig. 4 [41]. It is clear that the reaction is second order,
therefore the overall order of the rate law can be written as α +
β + γ = 2, and the original rate law can be written as
The experimental data show that the observed pseu-
do-second-order rate constant (kobs) is identical to the sec-
ond-order rate constant, which implies that γ = 0 in Eq. (2).
The results show that the reaction is zero- and second-order
with respect to 3 (γ = 0) and the sum of 1 and 2 (α + β = 2),
respectively.
In a fifth experiment, to determine the partial order of the
reaction with respect to 4-nitrobenzaldehyde (1), pseu-
do-order conditions were defined for the reaction of 2 (10
mmol/L), 3 (10 mmol/L), and 1 (10 mmol/L) in the presence
α
β
γ
rate = k [1] [2] [3] [Cat]
(1)
ovr
3.3. Mechanism
The partial order of reactant 3 under pseudo-order condi-
tions was determined in a separate (fourth) experiment, using
the same procedure and the following concentrations: reactant
of fructose (2.5 mmol/L) in H
O-EtOH (2:1). The results show
2
that the rate law can be expressed as
α
β
γ
rate = k [1] [2] [3] [Cat]
ovr
1
(10 mmol/L); reactant 2 (10 mmol/L); reactant 3 (1
α
rate = kobs[1]
(3)
mmol/L); and fructose (2.5 mmol/L). To obtain Eq. (2), the rate
law can be expressed as
β
γ
rate = k [2] [3] [Cat]
ovr
α
β
γ
rate = k [1] [2] [3] [Cat]
The original experimental absorbance versus time (full line)
at 385 nm, which exactly fits the experimental curve (dotted
line), is shown in Fig. 6.
ovr
γ
rate = kobs[3]
(2)
α
β
rate = kovr[1] [2] [Cat]
Fig. 6 shows that it is reasonable to accept that the partial
order with respect to reactant 1 is one (α = 1). The results of
the third (α + β + γ = 2) and fourth (γ = 0) experiments show
that the partial order β is one. The experimental rate law can
therefore be expressed as
1.45
1.40
1.35
1.30
1.25
rate = kobs[1][2]
[Cat]
(4)
k
obs = k
1
These results were used to produce a simplified scheme for
the proposed reaction mechanism (Fig. 2), and is shown in Fig.
7.
To determine which step in the proposed mechanism is the
rate-determining step, the rate law was written using the final
reaction step:
0
10
20
30
Time (min)
Fig. 4. Experimental absorbance changes (dotted line) and fit curve
solid line) against time for reaction of 4-nitrobenzaldehyde (1; 0.1
mmol/L), malononitrile (2; 0.1 mmol/L), and dimedone (3; 0.1 mmol/L
in presence of fructose (25 mmol/L) in H O-EtOH (2:1) at 385 nm and
5.0 °C.
5 4
rate = k [I ]
(5)
(
The steady-state approximation can be used for [I
1
], yielding
2
d[I4 ]
=
k [I ][Cat] - k [I ] = 0
(6)
4
3
5
4
2
dt

Sayyedeh Shadfar Pourpanah et al. / Chinese Journal of Catalysis 36 (2015) 757–763
761
18)
(
rate = kovr[1][2]
1.15
1.10
1.05
1.00
Eq. (18) indicates that the original order of the reaction is
two. Additionally, the orders of the reaction with respect to 1,
2, and 3 are one, one, and zero, respectively. Also, because of
the presence of k
1
in Eq. (18), it is clear that the first step (k ) is
1
the rate-determining step.
3.4. Effects of solvents and temperature
1
0
20
30
To assess the effects of changes in temperature and the sol-
Time (min)
vent environment on the reaction rate, experiments were per-
formed at various temperatures and in solvents with various
polarities, with the other conditions the same as those in the
earlier experiments.
Fig. 6. Pseudo-first-order fit curve (solid line) and original experi-
mental curve (dotted line) for reaction of 1, 2, and 3 in the presence of
fructose at 385 nm and 25.0 °C in H
2
O-EtOH (2:1).
Because the transition state (Step 1, Fig. 2) in the reaction
carries a dispersed charge, solvents with high dielectric con-
stants increase the reaction rate by stabilizing the transi-
k1
Step 1
1 + 2 + Cat
I1 + Cat
k2
I1 + Cat + 3
I + Cat-
tion-state species more than the reactants, lowering E
a
(Table
Step 2
Step 3
Step 4
Step 5
2
4).
k
3
I2 + Cat -
I3 + Cat
I3 + Cat
In the temperature range investigated, the relationship be-
tween the second-order rate constant (lnk ) of the reaction
k4
2
I4 + Cat
with reciprocal temperature conforms to the Arrhenius equa-
tion. This is shown in Fig. 8. The activation energy for the reac-
tion of 1, 2, and 3 (65.34 kJ/mol) was obtained from the slope
of the plot in Fig. 8.
k
5
I4
4 (product)
Fig. 7. Simplified scheme for proposed reaction mechanism.
The Eyring equation was used to determine the activation
‡
‡
parameters ΔH (activation enthalpy), ΔS (activation entropy),
k [I ][Cat] = k [I ]
(7)
(8)
4
3
5
4
‡
and ΔG (activation Gibbs energy) from the intercept and slope
Fig. 9). According to Equation (18), k is proportional to the
general reaction rate, therefore the activation parameters, i.e.,
The value of [I
4
] can be replaced in Equation (5) to give
(
1
rate = k [I ][Cat]
4
3
The [I ] can be determined from the following equation, by
3
applying the steady-state approximation:
Table 4
d[I3 ]
Rate constants for reaction of 4-nitrobenzaldehyde (1; 10 mmol/L),
malononitrile (2; 10 mmol/L), and dimedone (3; 10 mmol/L) in pres-
ence of fructose (2.5 mmol/L) in various solvents and at various tem-
peratures.
=
k [I ][Cat] - k [I ][Cat] = 0
(9)
3
2
4
3
dt
k [I ][Cat ] = k [I ][Cat]
-
3
2
4
3
By substituting Equation (9) into (8) and using some simple
mathematics, the following equation is obtained:
k1 × 10
T = 15 °C T = 20 °C
2.97
—
2
(L mol−1 min−1
)
Solvent
O-EtOH (2:1)
Methanol
Ethanol
ε
T = 25 °C T = 30 °C
6.92
—
H
2
60.9
32.6
24.3
4.73
—
11.75
14.82
8.25
rate = k [I ][Cat]
(10)
3
2
The steady-state approximation can then be used to deter-
—
—
—
2
mine [I ], as follows:
d[I2 ]
=
k [I ][Cat][1] - k [I ][Cat] = 0
(11)
2
1
4
3
3.0
dt
y = -7.8598x + 28.368
k [I ][Cat][1] = k [I ][Cat]
(12)
(13)
2.5
2.0
1.5
2
1
4
3
2
R = 0.9951
rate = k [I ][Cat][1]
2
1
d[I1 ]
dt
=
k [1][2][Cat] - k [I ][Cat] - k [3][I ][Cat] = 0
2 -1 1 2 1
(14)
1.0
k2[1][2]
[
I1 ] =
(15)
k-1 + k [3]
0.5
0.0
2
k [3][Cat]× k [1][2]
2
1
rate =
(16)
k-1 + k [3]
3.25
3.30
3.35
3.40
3.45
3.50
2
1
000/T
k
4
, k
constants cannot be those for the rate-determining step, but if
>>k−1, the following equations are obtained:
rate = k [1][2][Cat]and, k = k [Cat]
5
and k
3
are not involved in Eq. (16), therefore these rate
Fig. 8. Dependence of second-order rate constant (lnk
temperature for reaction of 1, 2, and 3 in the presence of fructose,
measured at a wavelength of 385 nm, in H
Arrhenius equation.
1
) on reciprocal
k
2
2
O-EtOH (2:1), based on the
(17)
1
ove
1

762
Sayyedeh Shadfar Pourpanah et al. / Chinese Journal of Catalysis 36 (2015) 757–763
1
1
1
1
0
0
0
0
0
.6
.4
.2
.0
.8
.6
.4
.2
.0
450
(a)
(b)
400
50
300
3
y = −7564.5x + 26.285
R = 0.9948
2
250
200
150
100
50
0
y = 26.322x − 7575.5
R = 0.9949
2
0
.00325 0.00330 0.00335 0.00340 0.00345 0.00350
/T
Fig. 9. Eyring plots for reaction of 1, 2, and 3 in the presence of fructose in H
285
290
295
300
305
T
1
2
O-EtOH (2:1).
‡
‡
‡
T, Tillequin F, Janin Y L. Bioorg Med Chem, 2008, 16: 8264
ΔG = 69.14 kJ/mol, ΔS = 20.99 J/(mol·K), and ΔH = 62.89
[
[
[
[
[
2] Symeonidis T, Chamilos M, Hadjipavlou-Litina D J, Kallitsakis M,
Litinas K E. Bioorg Med Chem Lett, 2009, 19: 1139
3] Narender T, Shweta, Gupta S. Bioorg Med Chem Lett, 2004, 14:
kJ/mol, can be calculated for the first step (rate-determining
1
step, k ), which is an elementary reaction, based on the Eyring
equation.
3913
4] Lakshmi V, Pandey K, Kapil A, Singh N, Samant M, Dube A. Phyto-
medicine, 2007, 14: 36
5] Kumar D, Reddy V B, Sharad S, Dube U, Kapur S. Eur J Med Chem,
4.
Conclusions
The overall order of the reaction for the formation of a
2009, 44: 3805
4H-tetrahydrobenzo[b]pyran derivative in the presence of
6] El-Agrody A M, El-Hakim M H, El-Latif M S A, Fakery A H, El-Sayed
fructose followed second-order kinetics, and the partial orders
with respect to 4-nitrobenzaldehyde (1), malononitrile (2), and
dimedone (3) were one, one, and zero, respectively. The results
show that rate of reaction increases in solvents with high die-
lectric constants at all temperatures. In the studied tempera-
ture range, the second-order rate constant of the reaction was
inversely proportional to the temperature, in agreement with
the Arrhenius equation. The first step of the proposed mecha-
E S M, El-Ghareab K A. Acta Pharm, 2000, 50: 111
[7] Konkoy C S, Fick D B, Cai S X, Lan N C, Keana J F W. Chem Abstr,
2001, 134a: 29313
[8] Niknam K, Borazjani N, Rashidian R, Jamali A. Chin J Catal, 2013,
34: 2245
[
9] Devi I, Bhuyan P J. Tetrahedron Lett, 2004, 45: 8625
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[
[
nism was identified as the rate-determining step (k
), and this
1
[
was confirmed based on the steady-state approximation.
The yield was a function of temperature, because the yield
increased with increasing temperature; at 40 °C, the product
was obtained in excellent yield, but the yield did not increase at
higher temperatures. Moreover, 20 mol% was chosen as a
suitable amount of catalyst for this reaction.
8
: 1724
[
[
[
[
13] Abdolmohammadi S, Balalaie S. Tetrhedron Lett, 2007, 48: 3299
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Graphical Abstract
Chin. J. Catal., 2015, 36: 757–763 doi: 10.1016/S1872-2067(14)60302-8
Fructose-catalyzed synthesis of tetrahydrobenzo[b]pyran
derivatives: Investigation of kinetics and mechanism
Sayyedeh Shadfar Pourpanah, Sayyed Mostafa Habibi-Khorassani*,
Mehdi Shahraki
University of Sistan and Baluchestan, Iran
R
CHO
O
O
O
CN
CN
Fructose (20 mol%)
O:EtOH (2:1)
CN
NH
+
+
We report kinetic results and detailed mechanistic studies for the syn-
thesis of a derivative of 4H-tetrahydrobenzo[b]pyran, based on a global
kinetic analysis method using UV-Vis spectroscopy.
R
H
2
O
2
1
2
3
0 o
4
C

Sayyedeh Shadfar Pourpanah et al. / Chinese Journal of Catalysis 36 (2015) 757–763
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