Kinetics and related studies of the formation of 2,3-dihydroquinazolin-4(1H)-ones in the presence of different benzaldehyde derivatives

Article abstract of DOI:10.1002/poc.3774

The kinetics and activation parameters for the reaction between 2-amino-benzamide and some benzaldehyde derivatives in the presence of formic acid have been reported and discussed. A linear plot of lnk vs l/T showed that the reactions obey the Arrhenius equation. Both the Arrhenius and the Eyring equations were used to calculate the activation energy. The effect of nitro groups was studied on different positions of benzaldehyde. For all substituents, the reactions followed second-order kinetics, and the partial orders of reactions were recognized with respect to each reactant. Comparisons between the magnitudes of ΔH^? and TΔS^?showed that the reactions were enthalpy controlled. The validity of the isokinetic relationship and the compensation effect was tested, and the isokinetic temperature (β) was obtained. A linear enthalpy-entropy plot (ΔH^?versusΔS^?)?showed that the compensation effect is established, and this process occurs via a same mechanism across a series of reactions. From the Van't Hoff and Exner's plots, the isokinetic temperature was obtained.

Full text of DOI:10.1002/poc.3774

Received: 22 June 2017
DOI: 10.1002/poc.3774
Revised: 23 July 2017
Accepted: 31 August 2017
R E S E A R C H A R T I C L E
Kinetics and related studies of the formation of 2,3‐
dihydroquinazolin‐4(1H)‐ones in the presence of different
benzaldehyde derivatives
Bahareh Mostafa | Mehdi Shahraki
| Sayyed Mostafa Habibi‐Khorassani
Department of Chemistry, University of
Abstract
Sistan and Balouchestan, Zahedan, Iran
The kinetics and activation parameters for the reaction between 2‐amino‐
benzamide and some benzaldehyde derivatives in the presence of formic acid
have been reported and discussed. A linear plot of lnk vs l/T showed that the
reactions obey the Arrhenius equation. Both the Arrhenius and the Eyring
equations were used to calculate the activation energy. The effect of nitro
groups was studied on different positions of benzaldehyde. For all substituents,
the reactions followed second‐order kinetics, and the partial orders of reactions
were recognized with respect to each reactant. Comparisons between the mag-
nitudes of ΔH‡ and TΔS‡showed that the reactions were enthalpy controlled.
The validity of the isokinetic relationship and the compensation effect was
tested, and the isokinetic temperature (β) was obtained. A linear enthalpy‐
entropy plot (ΔH‡versusΔS‡) showed that the compensation effect is
established, and this process occurs via a same mechanism across a series of
reactions. From the Van't Hoff and Exner's plots, the isokinetic temperature
was obtained.
Correspondence
Mehdi Shahraki, Department of
Chemistry, University of Sistan and
Balouchestan, PO Box 98135‐674,
Zahedan, Iran.
Email: mehdishahraki@chem.usb.ac.ir
KEYWORDS
compensation effect, dihydroquinazolin, isokinetic temperaturekineticssubstituent effects
1 | INTRODUCTION
area of different reactions have previously been reported
using the UV/vis technique.[3–9] The main purpose of this
The goal of any kinetic study is the investigation of how
different experimental conditions can influence the speed
of a chemical reaction and yield information regarding
the reaction's mechanism and transition state. In order
to study the nature of the reaction mechanism, it is impor-
tant to study the effect of different factors on the rate of
the reaction and determine the various kinetic and activa-
tion parameters. The isokinetic relationship is helpful in
determining whether a series of reactions are following
same mechanism.[1,2] A number of methods have been
developed to obtain experimental kinetic data and ana-
lyze them to arrive at a true explanation of the reaction
mechanism. Numerous kinetic researches over a large
study is to achieve a general overview on the kinetic
behavior of the reaction between 2‐aminobenzamide with
benzaldehyde in the presence of formic acid as a catalyst
for the generation of 2, 3‐dihydroquinazolin‐4(1H)‐ones
(Scheme 1). Quinazolin‐4(3H)‐ones are an important class
of fused heterocycles that are used as chemotherapeutic
agents for the treatment of diseases resulting from differ-
ent microorganisms, and currently there has been a major
expansion in the number of quinazolinone derivatives as
drugs.[10–18] 2, 3‐Dihydroquinazolinone derivatives have
been reported to possess a wide range of pharmacological
attributes such as anti‐inflammatory, analgesic,[19] antitu-
mor,[20] anticancer,[21] antibacterial,[22] and diuretic
J Phys Org Chem. 2017;e3774.
wileyonlinelibrary.com/journal/poc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/poc.3774

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MOSTAFA ET AL.
SCHEME 1 Reaction of the formation of 2, 3‐dihydroquinazolin‐
4(1H)‐ones
attributes.[23] These unique biological properties have
made quinazolinone synthetic studies over the years very
attractive.[24] It is notable that the kinetics and synthesis
studies have been reported for these reactions.[2,25]
Herein, we investigate the validity of the isokinetic
relationship and compensation effect in addition to the
kinetic studies.
FIGURE 1 The expanded absorption changes versus wavelength
in the safe region for the reaction between compound 1 (10−3 M)
and 4‐nitro benzaldehyde 2 (10−3 M) in the presence of formic acid
as a solvent. The upward direction of the arrow indicates the
progress of reaction versus time
2 | EXPERIMENTAL
2.1 | Chemicals and apparatus used
2‐Amino‐benzamide 1, some benzaldehyde derivatives 2
(which are listed in Table 1), and formic acid (as a solvent)
were obtained from Merck (Darmstadt, Germany), Acros
(Geel, Belgium), and Fluka (Buchs, Switzerland) and used
without further purifications. A Cary UV‐vis spectropho-
tometer model Bio‐300 with a 10‐mm light‐path quartz
spectrophotometer cell was employed throughout the cur-
rent work.
involving 10−3 M solutions of each compound (1and 2)
were recorded until the reaction was finished. The
progress of the reaction was monitored via expanded
absorbance changes as a function of wavelengths
(Figure 1). From these spectra and the single spectrum
of each reactant, the appropriate wavelength was
discovered, providing the opportunity to investigate the
kinetics and mechanism of the reaction. Determination
of the rate law and overall order of the reaction is the
main objective of the kinetic studies. Hence, increases
in the absorbance of the product were followed versus
time under same concentrations of each compound at
298.15 K and an appropriate wavelength of 390 nm
(Figure 2). Results showed that the experimental curve
(dotted line) fit the second‐order curve (solid line)
(β + α = 2). The second‐order rate constants k were
automatically evaluated using the standard equations
within the program.[26] All the reactions followed a
second‐order rate law at different temperatures. Same
2.2 | General procedure
The progress of the reaction between 2‐amino‐
benzamide1 and some benzaldehyde derivatives 2 (listed
in Table 1) in the presence of formic acid were studied
by UV‐vis spectrophotometer. The following procedures
were carried out. In the first experiment, 10−3 M solutions
of each reactant were prepared using formic acid as the
solvent. The relevant spectrum of each compound was
recorded at a wavelength range of 200 to 600 nm. After-
wards, the absorbance changes of the mixed solution
TABLE 1 The listed benzaldehyde derivatives which have been used for the investigated reactions in Scheme 1
2‐Nitrobenzaldehyde
3‐Nitrobenzaldehyde
4‐Nitrobenzaldehyde
4‐Methylbenzaldehyde
Benzaldehyde

MOSTAFA ET AL.
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kobs ¼ kove½catꢀ
(3)
3 | RESULTS AND DISCUSSION
3.1 | Kinetic and activation parameters
The kinetic investigation of the reactions was carried out
at different temperatures and same concentrations of each
reactant to obtain the activation and kinetic parameters.
The second‐order rate constants kobs were calculated at
different temperatures which are reported in Table 2.
The results show that the rate of the reactions was
increased at higher temperatures. When the Ln kove (rate
constant) is plotted against the inverse of the temperature,
1/T, a straight line is obtained which is in agreement with
the Arrhenius equation 5 (Figure 3).
FIGURE 2 The original experimental absorbance curve versus
time for the reaction between compound 1 (10−3 M) and 4‐nitro
benzaldehyde 2 (10−3 M) in the presence of formic acid as a solvent
at 293.15 K and 390 nm. The dotted line is the experimental values,
and the solid line is the fitted curve
Ea
−RT
k ¼ Ae
(4)
(5)
results were deducted for other benzaldehyde
derivatives (listed in Table 1) which relevant spectra
and experimental absorbance curve and fitted curve have
been reported in supplemental material files (SMF).
Pseudo‐order conditions indicated that the partial order
of the reaction was one with respect to each reactant
(α = 1) and (β = 1). For this case, the rate law can be
expressed as Equation 2. The subscripts exp and ove
denote experimental and overall, respectively.
Ea
Ln k ¼ LnA−
RT
The activation energies of the reactions were obtained
from the slopes of the curves in Figure 3. Other activation
parameters were calculated using the values of activation
energy and the following equations 1.
ꢀ ꢁ
ꢀ
ꢁ
k
T
kB ΔS‡
ΔH‡
RT
Ln
¼
Ln
þ
−
(6a)
(6b)
h
R
α
β
rateexp ¼ kove½1ꢀ ½2ꢀ ½catꢀ
(1)
(2)
ꢀ ꢁ
ꢀ
ꢁ
k
kB ΔS‡
ΔH‡
R
T Ln
¼ T Ln
þ
−
rateexp ¼ kobs½1ꢀ½2ꢀ
T
h
R
TABLE 2 Second‐order rate constants at various temperatures for the reaction between compound 1 and different substituents of com-
pound 2 in the presence of formic acid as the solvent
kobs
Substituent of compound 2
T(K)
293.15
72.3
(0.014)a
298.15
303.15
253.2
(0.010)a
308.15
344.0
(0.015)a
4‐Nitrobenzaldehyde
(reaction 1)
163.2
(0.018)a
3‐Nitrobenzaldehyde
(reaction 2)
57.3
(0.009)a
115.4
(0.011)a
155.7
(0.007)a
215.4
(0.012)a
2‐Nitrobenzaldehyde
(reaction 3)
29.9
(0.008)a
44.7
(0.009)a
59.9
(0.011)a
74.7
(0.012)a
Benzaldehyde
(reaction 4)
40
(0.009)a
46
(0.007)a
68.64
(0.004)a
107.47
(0.005)a
4‐Methylbenzaldehyde
(reaction 5)
21.47
(0.012)a
28.2
(0.014)a
44
(0.016)a
52
(0.015)a
aStandard deviation.

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MOSTAFA ET AL.
8
6
4
2
0
4-nitro
3-nitro
2-nitro
-H
FIGURE 3 The dependence of the
second‐order rate constant (Ln kove) on the
reciprocal temperature for the reaction
between compound 1 and different
substituents of compound 2 in the
presence of formic acid as a solvent
-methyl
3.24
3.2
3.28
3.32
3.36
3.4
3.44
1000/T
-3
-2
-1
0
-1400
-1000
-600
-H
-
methy
l
FIGURE 4 A, Eyring plot according to
Equation 7a for the reaction between
compound 1 and different substituent of
compound 2 in the presence of formic acid
as a solvent. B, Eyring plot according to
Equation 7b for the reaction between
compound 1 and different substituents of
compound 2 in the presence of formic acid
as a solvent
-H
-methyl
Linear
(4-nitro)
Linear
(4-nitro)
-200
292
200
297
302
307
312
1
0.003
0.0032
0.0034
1/T
follows that in the most solution phase studies, σ(ΔS‡)≈
σ(ΔH‡) × 0.003 K_1. This correlation has been mentioned
elsewhere.[27]
ΔG‡ ¼ ΔH‡−TΔS‡
(7)
The Arrhenius equation is often applied to gas‐phase
kinetics, whereas the Eyring equation is used to
describe the relationship between the reaction rate and
temperature for reactions in solution media, Equation 6a
or 6b.
The activation Gibbs free energy is essentially the
energy required for molecule (or a mole of them) to
undergo the reaction. Activation energies below 42 kJ
mol−1 generally indicate diffusion‐controlled processes,
and higher values represent chemically controlled reac-
tion processes, so the reactions of this study are chemi-
cally controlled.[28,29] Activation Gibbs's free energies are
considered to be the difference in free energy between
the activated complex and the reactants from which it
was formed. The large and positive ΔG≠ and ΔH‡ values
suggested that these reactions require energy to convert
reactants into products. As can be seen from the data in
Table 3, ΔH‡ is larger than TΔS‡for each of the substitu-
ents. Therefore, ΔG≠ and the rates of these reactions are
controlled by ΔH‡.[30] Furthermore, the large negative
values of ΔS‡ for reactions 3, 4, and 5 compared with reac-
tions 2 and 1 indicated that the activated complex for
reaction 3 (involving 2‐nitrobenzaldehyde) has a more
ordered or more rigid structure than the other reactions
(1and 2). Nevertheless, the positive values of ΔH‡ for
The values of the activation parameters were deter-
k
1
mined from a Ln ( ) vs plot Equation 6a and Figure 4
T
T
A. In addition, the activation parameters (ΔS‡and ΔH‡)
also could be calculated from the linearized form of
Eyring equation 6b shown in Figure 4B. Morever, ΔG‡ is
subsequently calculated from Equation 7.
Thus, the kinetic and activation parameters are accu-
mulated in Table 3. Herein, Eyring equations suggest that
the standard errors of ΔS‡ and ΔH‡ are related to each
other through Equation 8.
À
Á
À
Á
1
Tav
σ ΔS‡
¼
σ ΔH‡
(8)
In this equation, Tav is known to be the centre of the
temperature range that is used in this investigation. It

MOSTAFA ET AL.
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TABLE 3 Activation parameters (ΔH‡, ΔG‡ , ΔS‡, and Ea) for the reaction between compound 1 (10−3 M) and different substituent of
compound 2 (10−3 M) in the presence of formic acid as a solvent in accordance with 2 Equations 6a and 6b
4‐ Nitrobenzaldehyde (reaction 1)
ΔH‡ (kJ.mol−1
(74.5 3.8)a
(74.1 4.6)b
)
ΔG‡ (kJ.mol−1
(60.7 9.2)a
(60.7 9.2)b
)
ΔS‡(J.mol−1.K−1
(46.3 12.7)a
(44.7 15.5)b
)
TΔS‡(kJ.mol−1
)
Ea (kJ.mol−1
(77.0 3.5)c
)
A
13.5
13.1
4.31 × 1015
3‐Nitrobenzaldehyde (reaction 2)
(61.5 3.1)a
(61.5 3.1)b
(61.6 6.1)a
(61.6 6.0)b
(0.7 0.1)a
0.2
0.1
(64.3 2.9)c
(45.7 1.2)c
1.06 × 1013
3.58 × 109
3.4 × 1010
4.2 × 109
(−0.4 0.1)b
2‐Nitrobenzaldehyde (reaction 3)
(43.2 1.3)a
(43.0 1.3)b
(63.7 2.5)a
(63.7 2.4)b
(−68.8 4.3)a
(−69.3 4.3)b
20.1
20.3
Benzaldehyde (reaction 4)
(−51.5 8.9)a
(−50.46 9)b
(47.2 2.7)a
48.21 2.7 b
(63.2 5.3)a
(63.2 5.4)b
15.3
15.0
(50.38 2.5)c
(46.5 1.6)c
4‐Methylbenzaldehyde (reaction 5)
(−68.92 5.8)a
(44.0 1.7)a
(43.9 1.7)b
(64.63 3.4)a
(64.62 3.4)b
20.54
20.62
(−69.17 5.7)b
a. Obtained from Equation 6a.
b. Obtained from Equation 6b.
c. Obtained from Figure 3.
reaction 3 are less than both reactions 2 and 3. There-
fore, competition between both unfavorable
3.2 | Substituent effects
a
ΔS‡(negative and unfavorable) and favorable ΔH‡ (low
value) makes a difficult reaction of nitro‐substituent in
the orto position of the benzaldehyde ring (reaction 3)
relative to the other positions (meta and para in reac-
tions 2 and 1, respectively). Where comparing ΔG≠ values
for the reactions (Table 3), the activation energy for the
nitro‐substituent in the orto position (reaction 3) is less
than (meta and para in reactions 2 and 1, respectively),
so it is expected that the rate of reaction 3 will be more
than the reactions 2 and 1, but as shown in Equation 4 rate
constant is a combination of different factors such as
frequency factor and activation energy. The frequency
factor A is related to the frequency of collisions and
the probability that the collisions are favorably
oriented for the reaction. Ln A and ΔS‡ give informations
about the degree of order in the transition state.
(Structural effect).
In the present work, several experiments were carried
out to achieve further understanding about the effect of
the functional group on the rate of the reaction.
Results showed that the effectiveness of the investigated
substituent in increasing the rate of reaction follows the
following order:
4‐nitrobenzaldehyde > 3‐nitrobenzaldehyde > benzal-
dehyde > 2‐nitrobenzaldehyde > 4‐methylbenzaldehyde.
Nitro group is the electron‐withdrawing group
(EWG) and increases the reactivity of benzaldehyde with
nucleophiles so increases the rate of reaction, but
because of steric effect the rate of reaction in the pres-
ence of 2‐nitrobenzaldehyde(reaction 3) is lower than
reaction 4.
The rate of reaction in the presence of 4‐
methylbenzaldehyde is less than that of benzaldehyde;
because carbon is slightly more electronegative than
hydrogen, there will be a little dipole moment pulling
electron density away from hydrogen toward carbon.
This slight build‐up of electron density on the carbon
results in the methyl group having an electron
donating effect by induction, thus decreasing the rate
of reaction.
ΔS≠
R
þ2
ekBT
h
A ¼
e
(9)
Low values of Ln A correspond to negative values of
ΔS‡, suggesting that entropy reduces upon achieving the
transition state for reaction 3, 4, and 5 (compared with
reactions 2 and 1).

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MOSTAFA ET AL.
On the basis of experimental observations, 3 possibili-
ties can be considered.
First, if step3 (k3) are considered as the rate‐determin-
ing step (RDS), step2 (k2) should appear as the equilib-
rium state with forward (k2) and return (k‐2) rate
constants, respectively. So, the simplified scheme of the
proposed reaction mechanism can be stated (Figure 7) as:
By applying the steady‐state approximation, the gen-
eral rate law can be written:
k1k3 ½1ꢀ½2ꢀ½catꢀ
rate ¼
(10)
k−2½catꢀ½H2Oꢀ þ k3
When step3 is practically the RDS, the following
assumption is logical:
k1k3 ½1ꢀ½2ꢀ
k−2½catꢀ½H2Oꢀ>>k3 rate ¼
kobs
k−2½H2Oꢀ
k1k3
k−2½H2Oꢀ
¼
(10a)
(10b)
FIGURE 5 The proposed mechanism for the reaction between
compound 1 and compound 2 in the presence of formic acid for
the generation of 3 (product)
ratemech ¼ kobs½1ꢀ½2ꢀ
As a result, 5 significant points can be stated:
3.3 | Mechanism investigation
1. When step3 (k3) is the RDS, under this condition, the
rate law that was deduced from the mechanism is
ratemech = kobs [1, 2] (10b).
A simplified scheme of the proposed reaction mechanism
shown in Figure 5 is presented in Figure 6.
k1
I1
Step1
1
+
2
+
Cat
I1
Step2
12
+ Cat + H2O
k2
I2
Step3
3(product)
k3
FIGURE 6 Simplified scheme for the proposed reaction mechanism
k1
I1
Step1
1 +
2
+ Cat
fast
k2
k-2
I1
Step2
Step3
12
+
Cat + H2O
3(product)
RDS(slow)
k3
I2
FIGURE 7 Simplified scheme for the
reaction mechanism when step3 is the RDS

MOSTAFA ET AL.
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2. This equation follows a second‐order kinetics and
agrees with the experimental rate law, ratemech = kobs
[1, 2] (Equation 2).
ratemech ¼ kobs½1 ; 2ꢀ:
(11c)
3. When step3 (k3) is practically the RDS, intermediate
I2 is converted to main product 3 (see Figure 5) along
with a 6‐membered ring forming within compound.
As expected, formation of such a ring in step3
reduces the number of degrees of freedom which
subsequently slows the entropy down (ΔS‡>> 0).
4. Practically, only reaction 3 had a large negative value
of ΔS‡ ΔS‡= −68.8 j.mol−1.k−1), Table 3) with
participation of 2‐nitrobenzaldehyde in a reaction
environment; hence, it has an associative mechanism.
5. Therefore, for reaction 3, RDS is step3 (k3), and the
second‐order rate Law is Equation 10b with the
k3k1
1. This equation follows a second‐order kinetics and is
an agreement with the experimental rate law,
rateexp = kobs [1, 2] (Equation 2).
2. When step2 is practically the RDS, intermediate I1
with a rate constant (k2) is converted to intermediate
I2 through a dehydration process. In this case, I1 spe-
cies are divided into 2 species such as I2 and H2O; as
expected, the number of degrees of freedom increases
and subsequently speeds the enthalpy up (ΔS‡>> 0).
3. Practically, only reaction 1 had a large positive value
of ΔS‡( ΔS‡= 46.3 j.mol−1.k−1) with the participation
of 4‐nitrobenzaldehyde in the reaction environment;
hence, it has a dissociative mechanism. When ΔS‡ is
bigger than −10 j.mol−1.k−1, it generally predicates a
dissociative mechanism.[30] For this reason, reaction
2 with the participation of 3‐nitrobenzaldehyde fol-
lows a dissociative mechanism.
observed rate constant, kobs
=
K
−1H2O
Second, if step2 (k2) is considered as the RDS, step1
(k1) should appear as the equilibrium state with forward
(k1) and return (k‐1) rate constants, respectively. So, the
simplified scheme of the proposed reaction mechanism
can be expressed (see Figure 8) as:
4. Therefore, for both reactions 1 and 2, RDS is step2
(k2), and the second‐order rate law is Equation 11b
k2k1½caꢀ
So, the general rate law can be obtained as:
with the observed rate constant, kobs
=
K−1
k1k2 ½1ꢀ½2ꢀ½catꢀ
rate ¼
(11)
Third, when k‐1 k2, the simplified scheme becomes
Figure 9:
k−1 þ k2
When step2 is practically the RDS, the following
assumption is acceptable:
Herein, the general rate law can be stated as:
rate ¼ k1½1ꢀ½2ꢀ½catꢀ
(12)
k1k2 ½1ꢀ½2ꢀ½catꢀ
kobs
k
−1>>k2 rate ¼
k−1
kobs ¼ k1½catꢀ
(12a)
k1k2 ½catꢀ
¼
(11a)
(11b)
k−1
ratemech ¼ kobs½1ꢀ½2ꢀ
(12b)
ratemech ¼ kobs½1ꢀ½2ꢀ
Herein, 5 significant points can be exposed:
Equation 12b follows second‐order kinetics and agrees
with the experimental rate law (Equation 2). When step1
(k1) is the RDS, both reactants (1,2) with rate constant
(k1) along with a nucleophilic attack of compound 1 on
the carbonyl group of compound 2 are converted to I1.
1. when step2 (k2) is the RDS, under this circumstance,
the rate law that was obtained from the mechanism is
k1
I1
Step1
1 +
2
+ Cat
k-1
k2
I1
Step2
Step3
12
+
Cat + H2O
3(product)
RDS (slow)
fast
k3
I2
FIGURE 8 Simplified scheme for the
reaction mechanism when step2 is the RDS

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MOSTAFA ET AL.
k1
I1
Step1
1 +
2
+ Cat
RDS
(fast)
k2
I1
Step2
Step3
12
+ Cat + H2O
FIGURE 9 Simplified scheme for the
reaction mechanism when k‐1 k2
k3 (fast)
I2
3(product)
This conversion is accompanied with a reduction in ΔS‡,
which is in agreement with the recorded data for reac-
tions 1, 2, and 3 where ΔS‡<<0 in Table 3. Nevertheless,
when the nitro group is placed on the orto‐position of
the benzaldehyde ring, its steric effect prevents the nucle-
ophilic attack of the amine group of compound 1 on the
carbonyl group of compound 2 (see step1, Figure 5). For
this reason, the reaction is difficult and required high
values of ΔH‡, while it is not practically so high for the
2‐nitro substituent(reaction3) in Table 3. It seems that
in reaction 3, step3 (k3) with low value of ΔH‡ is a suitable
RDS, while step1 (k1) that needs high value of ΔH‡ which
couldn't be compatible with the low experimental value of
ΔH‡(ΔH‡=43.2 kj.mol−1) is not a good candidate for the
RDS of this reaction.
same rate (or equilibrium) constant. As shown in
Figure 10, plotting the enthalpy changes vs the entropy
changes gives a straight line. Obviously, there is a signifi-
cant linear correlation between the enthalpy an entropy
changes (correlation coefficient = 0.999) and, therefore,
an excellent compensation effect. The value of the
isokinetic temperature β is given by the slope of the curve
in Figure 10 (270/2 K).
As previously mentioned, the isokinetic effect can be
distinct from the compensation effect. Therefore, the cor-
relation between ΔH‡ and ΔS‡ does not serve as good evi-
dence for the existence of the isokinetic relationship.
Validity of the isokinetic relationship can be investi-
gated in different ways, 1 way of finding a real isokinetic
(or isoequilibrium) relationship is to plot the free energy
changes vs the temperature (Figure 11) and look for a
point of common intersection among the lines. If no point
of common intersection exists, then an isokinetic (or
isoequilibrium) relationship cannot be said to exist.
Figure 11 shows that there is a temperature at which all
the free energy of the set of reactions are fairly close to
each other (273.15 K), so there is an isoequilibrium effect.
In a series of compounds with little a difference in struc-
tures, which are undergoing a reaction by essentially the
same mechanism, the ΔG‡ values may be more or less
constant with relative changes in ΔH‡ and ΔS‡.[31]
4 | VALIDITY OF THE ISOKINETIC
RELATIONSHIP AND
COMPENSATION EFFECT
Where the isokinetic relationship or the compensation
effect for a series of reactions is sufficiently similar, one
may expect the same mechanism to be operating across
reactions. Historically, the isokinetic relationship and
compensation effect were considered to be synonymous,
but Lei Liu et al demonstrated that the compensation
effect and isokinetic (or isoequilibrium) effect are not nec-
essarily synonymous, and the occurrence of one does not
necessarily imply the occurrence of the other. The basic
aim of the present article is to clarify if the isokinetic rela-
tionship or compensation effect or both are appeared in
the mentioned reactions. Sometimes, it is found that there
is a linear relationship between the activation enthalpy
and entropy changes of the series of reactions. This behav-
ior is known as the compensation effect or, more pre-
cisely, enthalpy‐entropy compensation.
80
70
y = 270.26x + 61.913
60
50
40
30
ΔH‡ ¼ βΔS‡ þ α
(13)
0.02
-0.03
S kJ.mol-1)
-0.08
β is therefore named the isokinetic temperature, and it
is independent of temperature. It seems that at the tem-
perature β, all the reactions in the series should have the
(
FIGURE 10 Enthalpy‐entropy compensation plot

MOSTAFA ET AL.
9 of 10
90
5 | CONCLUSION
4-nitro
3-nitro
2-nitro
-H
The detailed kinetic investigation of the reactions between
2‐amino‐benzamide and some benzaldehyde derivatives in
the presence of formic acid as an acid‐catalyst and
solvent was calculated using UV/vis spectrophotometry
technique. The results can be summarized as follows:
It was experimentally found that the reactions
followed second‐order rate law, so the overall order of
the reactions is 2, and the partial order of the reaction,
with respect to each reactant, is one. Rate of reactions
speeds up at higher temperatures, which agrees well with
the Arrhenius equation. Activation parameters (ΔH‡, ΔS‡,
and ΔG‡) were obtained from the Eyring equation. Based
on these parameters, it was found that the reactions were
enthalpy controlled for the investigated systems. Based on
the experimental data, the second step of the suggested
mechanism was identified as a rate determining step
(k2) with a second‐order rate law, when para or meta‐sub-
stituents were used as reactants during the reaction.
According to the experimental data (activation parame-
ter), the third step of the proposed mechanism was
determined as a rate determining step (k2) with the
second‐order rate law, when the meta substituent
was employed as reactant within the reaction
environment. A linear relationship in the enthalpy‐
entropy plot (ΔH‡ versus ΔS‡) showed that the compensa-
tion effect is established and this process occurs via a
same mechanism along the series of reactions. Existence
of a common intersection point of Van't Hoff lines serves
as evidence for the isokinetic relationship. The value of
the isokinetic temperatures, β, which are obtained from
Exner's plot, are in good agreement with the values that
are calculated from Van't Hoff plots.
80
70
60
50
4-methyl
40
150
250
350
450
550
T/K
FIGURE 11 Van't Hoff plot
Exner has recommended an alternative method for
calculating the isokinetic relationship and the value of β.
It consists of plotting the logarithms of the rate constants
at 2 temperatures (T2 > T1) against each other according
to Equation 14.
log k2 ¼ a þ blog k1
(14)
The value of the isokinetic temperature β can be calcu-
lated from the following expression
T2T1ðb−1Þ
β ¼
(15)
T2b−T1
In this study, a plot of log k2 (at 298/15 K) vs log k1
(at 293.15 K) (Figure 12) was found to be linear. The
value of β calculated by this method is 282.6 K, which
is in relative agreement with that evaluated from
Figures 11 (273.15) and 10 (270.2 K).
ACKNOWLEDGEMENT
2.4
2.2
2
We gratefully acknowledge the financial support received
from the Research Council of the University of Sistan and
Baluchestan.
1.8
1.6
ORCID
Mehdi Shahraki http://orcid.org/0000-0003-0447-7263
1.4
1.2
1
y = 1.4504x-0.5208
REFERENCES
[1] V. K. Gupta, P. Satya, A. Kumar, R. Gupta, N. Jain,
Thermochim. Acta 1989, 140, 197.
1.2
1.4
1.6
1.8
2
[2] B. Mostafa, S. M. Habibi‐Khorassani, M. Shahraki, J. Phys. Org.
Chem. 2016, 1, 1.
logk1
FIGURE 12 Exner's plot (relationship between log k1 (at
T1 = 293.15 K) and log k2 (at T2 = 298.15 K)
[3] M. Shahraki, S. M. Habibi‐Khorassani, J. Phys. Org. Chem. 2015,
28, 396.

10 of 10
MOSTAFA ET AL.
[4] M. Dehdab, S. M. Habibi‐Khorassani, M. Shahraki, Catal. Lett.
2014, 144, 1790.
[22] U. S. Hurmath, K. R. Gayam, T. Aravazhi, Journal of Applied
Pharmaceutical 2013, 3(10), 136.
[5] M. Shahraki, S. M. Habibi‐Khorassani, M. Dehdab, RSC Adv.
2015, 5, 52508.
[23] H. Lai, H. Dou, S. Aravapalli, T. Teremoto, G. Ushington, T. M.
Mwania, K. R. Alliston, D. M. Eichhorn, R. Padmanabhan, W.
C. Groutas, Bioorg. Med. Chem. 2013, 21(1), 102.
[6] M. Shaharaki, S. M. Habibi‐Khorassani, S. S. Purpanah, Biosci.
Biotech. Res. Asia 2016, 13, 715.
[24] M. R. Mousavi, J. Aboonajmi, M. T. Maghsoodlou, N. Hazeri,
S. M. Habibi‐Khorassani, M. Safarzaei, Lett. Org. Chem. 2013,
10, 171.
[7] S. S. Pourpanah, S. M. Habibi‐Khorassani, M. Shahraki, Chin. J.
Catal. 2015, 36, 757.
[25] M. T. Maghsoodlou, N. Hazeri, S. Esfandiari, S. Kiaee, A. Jasem,
[8] S. M. Habibi‐Khorassani, M. T. Maghsoodlou, M. Shahraki, M.
A. Poorshamsoddin, M. Karima, M. Abbasi, Iran. J. Catal. 2015,
5, 79.
M. Lashkari, P. Dastooran, Res Pharm Sci 2012, 7, 509.
[26] L. M. Schwartz, R. I. Gelb, Anal. Chem. 1978, 11, 1592.
[9] S. M. Habibi‐Khorassani, A. Ebrahimi, M. T. Maghsoodlou, O.
Asheri, M. Shahraki, N. Akbarzadeh, Y. Ghalandarzehi, Int J
ChemKinet 2013, 45, 596.
[27] H. Espenson, Chemical Kinetics and Reaction Mechanisms, 2nd
ed. Vol. 158, McGraw‐Hill, New York 1995.
[28] D. B. Abdala, I. R. DaSilva, M. Vergütz, D. L. Sparks,
[10] M. A. Alafeefy, Journal of Saudi Chemical Society 2011, 15, 337.
Chemosphere 2015, 119, 504.
[11] N. Boshta, F. A. El‐Essawy, M. Ammar, A. E. Ismail, J. Reprod.
Fert 2016, 147, 2031.
[29] D. B. Abdala, P. A. Northrup, Y. Arai, D. L. Sparks, J. Colloid
Interface Sci. 2015, 437, 297.
[12] K. A. Kumar, P. Jayaroopa, G. Kumar, Int. J. ChemTech Res
2012, 4(4), 1782.
[30] J. J. Franck, Phys. Chem. B 2011, 115, 1689.
[31] L. Liu, Q. X. Guo, Chem. Rev. 2001, 101, 673.
[13] R. Rajput, A. P. Mishra, Int. J. Pharm. Pharm. Sci 2012, 4(2), 66.
[14] J. Khurana, S. Kumar, Green Chem. Lett. Rev. 2011, 4, 321.
[15] V. Dongala, P. Tigulla, J. Chem. Pharm. Res 2013, 5(4), 340.
[16] S. Rajasekaran, G. Rao, Pharm. Lett 2012, 4(2), 470.
SUPPORTING INFORMATION
Additional Supporting Information may be found online
in the supporting information tab for this article.
[17] M. Mansing, P. Dattaprasad, J. Chem. Sci 2016, 128, 657.
[18] K. Rajaka, N. R. Penumati, K. Nagaiah, Y. Poornachandra, G.
Kuma, Synth. Commun. 2015, 45, 1893.
How to cite this article: Mostafa B, Shahraki M,
Habibi‐Khorassani SM. Kinetics and related studies
of the formation of 2,3‐dihydroquinazolin‐4(1H)‐
ones in the presence of different benzaldehyde
derivatives. J Phys Org Chem. 2017;e3774. https://
doi.org/10.1002/poc.3774
[19] G. V. R. Sharma, R. R. Alice, B. Devi, Nat Prod Chem Res
2014, 2, 1.
[20] E. Vitaku, D. Smith, J. Njardarson, J. Med. Chem. 2014, 57(24),
10257.
[21] E. Jafari, M. Rahmani Khajouei, F. Hassanzadeh, G.
Hossein Hakimelahi, G. Ali Khodarahmi, Res Pharm Sci
2016, 11(1), 1.