The mechanism of aromatic nucleophilic substitution reaction between ethanolamine and fluoro-nitrobenzenes: An investigation by kinetic measurements and DFT calculations

Article abstract of DOI:10.1002/poc.1817

We have studied the kinetics and elucidated the mechanism by DFT calculation of the reaction between ethanolamine (EOA) and 1-fluoro-2,4- dinitrobenzene (DNFB) in acetonitrile and toluene. To determine the contribution of the nitro group, the activation energy of the reaction between ethanolamine and 1-fluoro-2-nitrobenzene (MNFB) vs. DNFB was determined in acetonitrile and calculated by DFT method. Kinetic measurements reveal that the reaction is faster in acetonitrile than in toluene. The reaction follows overall second-order kinetics: first order with respect to both EOA and DNFB which is similar to the results reported for reaction between other primary amines and 1-substituted-2,4-dinitrobenzenes. The calculations by using DFT methods reveal that the mechanism of the reaction involves the formation and decomposition of a Meisenheimer complex (MC). DFT calculations also reveal that the activation energy of the reaction is highest in vacuum and decreases with increasing polarity of the solvent reaching a minimum in acetonitrile. In addition, activation energies obtained by both DFT calculations and experiments show that the reactivity of MNFB is less than that of DNFB showing the effect of the 4-nitro group.

Full text of DOI:10.1002/poc.1817

Research Article
Received: 21 August 2010,
Revised: 27 September 2010,
Accepted: 28 September 2010,
Published online in Wiley Online Library: 7 December 2010
(
wileyonlinelibrary.com) DOI 10.1002/poc.1817
The mechanism of aromatic nucleophilic
substitution reaction between ethanolamine
and fluoro-nitrobenzenes: an investigation by
kinetic measurements and DFT calculations
a
a
a
a
a
K.B. Jose , J. Cyriac , J. T. Moolayil , V.S. Sebastian and M. George *
We have studied the kinetics and elucidated the mechanism by DFT calculation of the reaction between ethanolamine
(EOA) and 1-fluoro-2,4-dinitrobenzene (DNFB) in acetonitrile and toluene. To determine the contribution of the nitro
group, the activation energy of the reaction between ethanolamine and 1-fluoro-2-nitrobenzene (MNFB) vs. DNFB was
determined in acetonitrile and calculated by DFT method. Kinetic measurements reveal that the reaction is faster in
acetonitrile than in toluene. The reaction follows overall second-order kinetics: first order with respect to both EOA
and DNFB which is similar to the results reported for reaction between other primary amines and
1-substituted-2,4-dinitrobenzenes. The calculations by using DFT methods reveal that the mechanism of the reaction
involves the formation and decomposition of a Meisenheimer complex (MC). DFT calculations also reveal that the
activation energy of the reaction is highest in vacuum and decreases with increasing polarity of the solvent reaching a
minimum in acetonitrile. In addition, activation energies obtained by both DFT calculations and experiments show
that the reactivity of MNFB is less than that of DNFB showing the effect of the 4-nitro group. Copyright ß 2010 John
Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper.
Keywords: activation energy; aromatic nucleophilic substitution; DFT calculation; Meisenheimer complex; solvent effects
involves the formation and decomposition of MC between
INTRODUCTION
thiomethoxide ion and 1-chloro-2,4-dinitrobenzene. The rate-
determining step is the formation of the MC and the calculated
energy barrier for its decomposition to products is very small.
The results of the study have been utilized for the theoretical
modeling of the enzyme catalyzed displacement of chloride ion by
Aromatic nucleophilic susbstitution reactions involving primary
amines are an important class of organic synthetic reactions and
continue to inspire studies of kinetics and mechanisms.
[
1–10]
Studies have revealed that the displacement of the substituent
at 1- position is faster when the aromatic ring contains
electron-withdrawing substituents at ortho and para pos-
[
14]
DFT (B3LYP/6-311þG**) and PM3 semi-empirical methods.
Other examples are the nucleophilic displacement of halide
[15]
[2,3]
itions.
Mechanisms involving the formation and decompo-
by another halide ion
and fluoride by ammonia, explored by
[
16]
sition of Meisenheimer complexes (MC) have been proposed
DFT calculations.
DFT Calculations, at B3LYP/6-31G* level of
[
4,5]
for S Ar reactions on the basis of kinetic studies
and
Amine catalysis for the decomposition
of MC has been suggested on the basis of kinetic measure-
theory, have been utilized to calculate the energy profile of the
reaction between ammonia and polyfluorobenzene to arrive at
the relative energies of the transition states for the formation and
decomposition of the MC, indicated as the rate-determining step.
The effect of solvent on the aromatic nucleophilic substitution
reaction between azide ion and 4-fluoronitrobenzene has been
N
[
9,10]
summarized recently.
[
5]
ments. The effect of electron-withdrawing substituents and
solvents on the rate of the displacement of fluorine, chlorine
or phenoxy groups at the 1-position by primary and secondary
amines. Most reports on kinetic measurements concur that the
reaction is overall second order: first order with respect to both
substrate and amine; and the rate-determining step is the
formation of the MC.
[
17]
investigated using DFT calculations. However, the mechanism
of displacement of aromatic halides by primary amines has not
been explored theoretically. In addition, the preferred method
for the synthesis of N-(2-nitroaryl)aminoethanol involves either
[
18,19]
Molecular orbital calculations using Density Functional Theory
the displacement of halide using ethanolamine
Smiles rearrangement of 2-(nitrophenoxy)ethylamine.
or the
[
20]
(
DFT) is being increasingly used for deducing and understanding
[
11]
mechanisms of organic reaction in the molecular level.
The
mechanisms of few aromatic nucleophilic substitution reactions
have been investigated by performing theoretical calculations by
*
Correspondence to: M. George, Department of Chemistry, Sacred Heart
College, Thevara, Kochi 682013, India.
E-mail: georgem_mathai@yahoo.co.in
[
10,12]
other methods.
displacement of chloride from 1-chloro-2,4-dinitrobenzene by
thiomethoxide ion (CH -S-) was investigated by both Hartree-
For example, the mechanism of nucleophilic
3
a
K. Jose, J. Cyriac, J. T. Moolayil, V. Sebastian, M. George
[
13]
Fock and MP2 using 6–31þG** basis set.
The mechanism
Department of Chemistry, Sacred Heart College, Thevara, Kochi 682013, India
J. Phys. Org. Chem. 2011, 24 714–719
Copyright ß 2010 John Wiley & Sons, Ltd.

INVESTIGATION BY KINETIC MEASUREMENTS
Molecular modeling
All DFT calculations both in vacuum and in solution phase (in
ethanol, toluene, diethylether, and acetonitrile) were carried out
[
21]
using Spartan 08 software package.
Geometry optimizations
were carried out at B3LYP/6-31G* and B3LYP/6-311G* (vacuum)
levels of theory to determine the energies of the reactants,
products, transitions states, and intermediates. For the calcu-
[
22]
Scheme 1. The reactions under study.
lations of the solvation models (SM8) geometry optimizations
were performed using the B3LYP/6-31G* method. The relative
energies (relative enthalpies of formation/reaction) of the
intermediates, transition states, and products were computed
relative to the total energies of the reactants.
We report the investigation of the displacement of fluoride from
-fluoro-2,4-dinitrobenzene (DNFB) or 1-fluoro-2-nitrobenzene
MNFB) by ethanolamine (EOA) a primary amine by kinetic
1
(
measurements. We employed molecular modeling by DFT methods
to confirm the mechanism of these reactions (Scheme 1). The kinetic
measurements were conducted in acetonitrile and toluene to study
the effect of solvent polarity on the rate of reaction. Furthermore, the
effect of solvent on the activation energy of the reaction has been
explored by applying solvation models (SM8 model, Spartan v. 8) to
calculate the activation energies required for the displacement of
fluorine in various solvents having different dielectric constants.
RESULTS AND DISCUSSIONS
Kinetic studies
The reactions of ethanolamine with DNFB, and MNFB yield
products 3 and 4 formed by the displacement of fluorine in
quantitative yields at room temperature (Scheme 1). From the
UV/VIS spectra, the lmax of 3 and 4 were determined in
acetonitrile to be 351 nm (345 nm in toluene) and 428.5 nm,
respectively.
EXPERIMENTAL
The rate of reaction of ethanolamine with DNFB in acetonitrile
at 313K was studied at several amine concentrations. In all runs
the DNFB concentration was much less than that of amine to
maintain pseudo-first-order kinetics. The observed rate constant
Synthesis of the products
Products 3 and 4 (Scheme 1) were synthesized by reaction
between 1-fluoro-2,4-dinitrobenzene and 1-fluoro-2-nitrobenzene,
respectively, with excess of ethanolamine in acetonitrile at room
Y
k increased linearly with increase in the initial concentration of
[18]
ethanolamine used, Table 1. The second-order rate constants, kA
temperature.
The structures of the purified products were
obtained from the relation k ¼ k /[EOA], were practically
confirmed by IR, NMR, and mass spectral data (Supporting
Information). The UV/VIS spectra were recorded to determine
the lmax of the products.
A
Y
constant, indicating, first-order dependence of the rate on the
[
EOA]. The first-order dependence of rate on the [EOA] is further
confirmed by the log k vs. log [EOA] plots, which are linear with
Y
slopes of almost unity (linear regression method gives
r ¼ 0.99027 and slope ¼ 1.086). The study of the kinetics of
reaction between EOA and DNFB was repeated in toluene at 303K
at several amine concentrations, where again low concentrations
of DNFB were maintained to preserve pseudo first-order rate
conditions. The rate of reaction was likewise first-order on [EOA]
and less than that in acetonitrile (Table 2).
When the progress of the reaction was studied with different
initial concentrations of the DNFB, keeping the [EOA] constant,
in acetonitrile at 313K under pseudo first-order conditions, plots
of log absorbance versus time were found to be linear which
indicates first-order dependence of rate on the [DNFB]. This was
Kinetic measurements
The progress of reactions was monitored by measuring the
increase in the absorbance of the reaction mixture (at intervals
of 10 s) at the lmax of the product, N-2,4-dinitrophenyl
-
2-aminoethanol. Absorbance was measured by using Shimadzu,
UV 1800 double beam UV/VIS spectrometer equipped with
thermoelectrically controlled) thermo-stated cell holder and
(
UVProbe software. To start a kinetic run, a stock solution of DNFB
in acetonitrile was added into a thermostated cell containing
the solution of the primary amine such that the cell contained
a total of 3 ml of the reaction mixture. In the reference beam,
a cell containing pure solvent was kept (acetonitrile or toluene
was used as solvent). All kinetic runs were carried out under
pseudo-first-order conditions with the substrate concentration
Table 1. The observed rate constants at various concen-
trations of EOA
ꢀ
5
of the order of 10 M. For each kinetic run a time course graph
is obtained by plotting the absorbance against time, for a set
convenient time by using the UVProbe software and a kinetic
k
¼ k
/[EOA]
c
mol L s
A
ꢀ
3
ꢀ2 ꢀ1
ꢀl
ꢀ1
‘
‘
point-pick’ report which gives the absorbance at any time,
t’ was generated. By assuming 100% conversion, the absorbance
S. No.
[EOA]/10
M
k
c
/10
S
1
2
3
4
5
2.26
3.40
4.53
5.10
7.94
1.05
4.65
4.22
3.79
4.00
4.16
a
at completion of reactions (A ) was determined by plotting a
calibration graph between the absorbance of the isolated
product at its lmax and molar concentration for a series of
t
standard solutions. The absorbance at any time (A ) was obtained
by subtracting the initial absorbance from the measured value.
Pseudo-first-order rate constants (kobs) were obtained by a linear
least-squares fit of the experimental data, absorbance vs. time
1.43
1.72
2.04
3.30
ꢀ5
[DNFB] ¼ 2.671 ꢁ 10 M; Temperature ¼ 313K; Solvent: aceto-
nitrile.
(
Supporting Information).
J. Phys. Org. Chem. 2011, 24 714–719
Copyright ß 2010 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

K. B. JOSE ET AL.
an overall second-order kinetics showing first order with respect
to MNFB and ethanolamine (Table 3). The Arrhenius activation
energy was determined at 62.4 kJ/mol (Table 4).
Table 2. The observed rate constants at various concen-
trations of ethanolamine
ꢀ3
S.
No.
k ¼ k /[EOA] ꢁ 10
ꢀl ꢀ1
A
c
ꢀ
3
ꢀ5 ꢀ1
[EOA]/10
M
k
c
/10
S
mol L s
Comparison of rates and activation energies
In summary, second-order rate coefficients, k
experimental pseudo-first-order rate coefficients, k , are listed in
Table 3. Comparison of the rate constants, k , reveals that rate of
A
the reaction between ethanolamine and DNFB in acetonitrile is
much greater than corresponding rate in toluene medium with
corresponding activation energies of 17.8 and 24.4 kJ/mol,
respectively. The kinetic data indicate a general tendency for a
A
, determined from
1
2
3
4
5
2.74
5.48
8.23
10.97
13.71
1.99
4.19
6.12
8.84
12.59
7.28
7.64
7.44
8.57
9.18
Y
[
toluene.
DNFB] ¼ 4.055 ꢁ 10ꢀ5 M;
Temperature ¼ 303 K;
Solvent:
A
decrease in k values with the less polar nature of toluene.
In addition, the rate of reaction of ethanolamine with MNFB
in acetonitrile is much lower than that of DNFB with
Table 3. Second-order rate constants, k
A
, obtained by dividing the pseudo-first-order rate constant by the [EOA] for the nucleophilic
displacement of fluorine from DNFB and MNFB with EOA
Trial No.
DNFB in acetonitrile
DNFB in toluene
MNFB in acetonitrile
ꢀ
3
ꢀ5
ꢀ3
[
DNFB] ¼ 2.671 ꢁ 10
Temp ¼ 313 K
M
[DNFB] ¼ 4.052 ꢁ 10
M
[MNFB] ¼ 1.615 ꢁ 10
M
Temp ¼ 303 K
Temp ¼ 313 K
ꢀ
1
ꢀ1
ꢀ1 ꢀ1
ꢀ1 ꢀ1
s )
k
A
(L mol
s
)
k
A
(L mol
s
)
k
A
(L mol
ꢀ3
ꢀ3
ꢀ3
ꢀ3
ꢀ3
ꢀ3
ꢀ3
ꢀ3
ꢀ3
ꢀ4
1
2
3
4
4.65(2.26 ꢁ 10
4.22(3.40 ꢁ 10
3.79(4.53 ꢁ 10
4.00(5.10 ꢁ 10
)
)
)
)
7.28 ꢁ 10 (2.74 ꢁ 10
)
)
)
1.96 ꢁ 10 (0.0487)
ꢀ4
7.64 ꢁ 10 (5.48 ꢁ 10
2.08 ꢁ 10 (0.122)
ꢀ3
ꢀ4
7.44 ꢁ 10 (8.23 ꢁ 10
2.28 ꢁ 10 (0.146)
ꢀ3
ꢀ3
ꢀ4
8.05 ꢁ 10 (10.97 ꢁ 10
)
2.46 ꢁ 10 (0.195)
Values in parenthesis represent molar concentrations of EOA.
Table 4. Rate constants for the reaction of EOA with DNFB and MNFB at various temperatures (pseudo-first-order w.r.t halide)
Temp (K)
DNFB in acetonitrile
DNFB in toluene
MNFB in acetonitrile
ꢀ
5
ꢀ5
ꢀ3
[
[
DNFB] ¼ 2.6696 ꢁ 10
M
[DNFB] ¼ 4.0552 ꢁ 10
[DNFB] ¼ 1.6148 ꢁ 10
ꢀ
3
ꢀ1
ꢀ3 ꢀ1
ꢀ1
EOA] ¼ 4.5343 ꢁ 10
s
[EOA] ¼ 0.2272 ꢁ 10
s
[EOA] ¼ 0.1218 s
ꢀ2
ꢀ2
ꢀ2
ꢀ2
ꢀ2
ꢀ5
ꢀ6
ꢀ6
2
2
3
3
3
93
98
03
08
13
1.09 ꢁ 10
1.26 ꢁ 10
1.41 ꢁ 10
1.61 ꢁ 10
1.72 ꢁ 10
4.67 ꢁ 10
4.77 ꢁ 10
ꢀ5
5.75 ꢁ 10
8.49 ꢁ 10
ꢀ5
ꢀ6
6.12 ꢁ 10
11.98 ꢁ 10
ꢀ5
ꢀ6
7.86 ꢁ 10
16.33 ꢁ 10
ꢀ6
—
26.55 ꢁ 10
further confirmed from the observation that, the pseudo-
first-order rate constants k , were independent of the initial
Table 5. The relative energies of the reactants, products,
intermediates, and transition states for the reaction between
DNFB and EOA, in vacuum by DFT calculations (kJ/mol)
Y
concentration of DNFB (Table 3). Furthermore, the reaction was
found to be first order with respect to DNFB in toluene; the rate
constant of the reaction is less than that in acetonitrile. Since the
reaction is first order both in the concentration of the DNFB and
the amine, the reaction has an overall order of 2. The Arrhenius
activation energies determined by studying the variation of rate
with temperature (ln second-order rate vs. 1/T) are 17.8 kJ/mol in
acetonitrile and 24.4 kJ/mol in toluene (Table 4).
Species
B3LYP 6_31G* B3LYP 6_311G*
DNFB þ 2EOA
DNFB þ EOA complex
TS1
0
0
ꢀ18.28
ꢀ21.34
35.16
35.33
The rate of reaction of MNFB with ethanolamine in acetonitrile
was similarly determined at different ethanolamine concen-
trations (Supporting Information). Pseudo-first-order constants
were observed and the second-order rate constants calculated
show constancy within experimental limits. The reaction follows
MC
29.23
30.12
P1 þ P2 Product complex
Product (P1 þ P2)
P1þ HF
ꢀ168.86
ꢀ73.17
5.82
ꢀ178.78
ꢀ88.43
ꢀ11.03
350.66
Anion þ (EOA þ H)
361.57
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INVESTIGATION BY KINETIC MEASUREMENTS
Usually, S Ar reaction involves two steps: the first step is the
N
formation of a MC and second is the decomposition of MC. The
total energies of the reactants, intermediates, transition states,
and products calculated by DFT methods are given in Table 5. The
possible formation of a complex between the reactants ethanola-
mine (EOA) and 1-fluoro-2,4-dinitrobenzene (DNFB-EOA complex),
an ion–dipole complex held together by electrostatic attraction was
explored (Scheme 2). The lowest energy structure obtained for the
electrostatic complex of the reactants, DNFB-EOA complex, is
18.3kJ/mol (gas-phase, GP) more stable than the reactants; in the
complex the hydrogen atom of the amino group of the primary
amine interacts (H-bonding) with the F atom and the oxygen
atom of the nitro group. The attack of the primary amine at the
C1 position leads to the formation of the MC, a zwitterionic
intermediate, which is 29.2 kJ/mol less stable than the reactants
(Fig. 1a). We note that the MC is more stable than reactants
for solution phases (Scheme 2). The relative energy of the
transition state (TS1), Fig. 1b, for the formation of MC is 35.2 kJ/
mol (GP) which indicate that the MC forms a shallow potential
well. Kinetic data reveal the rate-determining step of the reaction
is the formation of the MC.
˚
Figure 1. (a) MC; C—F bond length ¼ 1.441 A; C—N bond
˚
length ¼ 1.572 A; FCN bond angle ¼ 95.768; (b) TS1; C—F bond
˚
˚
length ¼ 1.390 A; C—N bond length ¼ 1.812 A; FCN bond angle ¼ 91.998
corresponding activation energy of 62.4 kJ/mol, which indicates
that the absence of the nitro group at the 4-position greatly slows
the rate of the reaction.
Theoretical calculations
DFT calculations were performed in vacuum and in various solvents
to explore possible mechanisms for the displacement of fluorine
from 1-fluoro-2,4-dinitrobenzene by ethanolamine (Experimental).
To understand the stochiometry of the reaction and
decomposition pathway of the MC, three possible product
Scheme 2. Mechanism of reaction of EOA and DNFB based on DFT calculations (B3LYP/6-31G*). Energies (relative to DNFB þ 2EOA) are given in kJ/mol:
a) in vacuum, (b) in toluene, (c) in ethanol, and (d) in acetonitrile
(
J. Phys. Org. Chem. 2011, 24 714–719
Copyright ß 2010 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

K. B. JOSE ET AL.
Table 6. The relative energies of the reactants, products, intermediates, and transition states for the reaction between DNFB and
EOA, in acetonitrile, ethanol, and toluene obtained by DFT calculations (B3LYP/6-31G*) (kJ/mol)
Species
Acetonitrile
Ethanol
Toluene
DNFB þ 2EOA
DNFB þ EOA complex
TS1
0
0
0
ꢀ7.82
ꢀ5.93
ꢀ12.90
22.24
23.66
31.12
MC
P1 þ P2 product complex
ꢀ12.12
ꢀ217.67
ꢀ95.55
ꢀ18.02
ꢀ153.04
ꢀ96.16
ꢀ13.94
ꢀ156.51
ꢀ83.76
Product (P1 þ P2)
Table 7. Activation energies for the reaction of DNFB with ethanol amine in vacuum and in various solvents (kJ/mol)
Method
Vacuum
Toluene
Diethyl ether
Ethanol
Acetonitrile
DMF
MO calculation, B3LYP/6-31G*
Experimental value
35.16
—
31.12
24.36
28.89
—
23.66
—
22.22
17.82
21.92
combinations were considered: (1) N-(2,4-dinitrophenyl)amino
ethanol (P1) and HF (Eqn (1)), (2) N-(2,4-dinitrophenyl)amino
ethanol (P1), fluoride ion and protonated ethanolamine
which P1 is electro-statically bound to HF and ethanolamine,
which is much lower in energy than products (Scheme 2). The
relative energy of the product complex is calculated as
ꢀ168.86 kJ/mol while the relative energy of the sum of the
products (P1 þ P2) is ꢀ73.17 kJ/mol (Table 5). Therefore, DFT
calculations in vacuum indicate that the reaction involves two
steps: the first is the slow formation of an MC and followed by its
decomposition catalyzed by ethanolamine (Scheme 2).
To understand the effect of solvent polarity on the activation
energy of the reaction, the total energies of the transition states
and intermediates in acetonitrile, ethanol, and toluene were
estimated by repeating the DFT calculations using B3LYP/6-31G*
method, using solvation models (Experimental). The relative
energies of the transition states (TS1) for the formation of the
MC and that of MC are found to be lower in acetonitrile, ethanol,
and toluene compared to that in vacuum (Scheme 2, Table 6).
In addition, the relative energies of the MC in all three solvents
are found to be lower than the sum of the energies of the
reactants, hence exothermic. Moreover, the relative energies of
(
EOA þ H), (3) N-(2,4-dinitrophenyl)amino ethanol (P1) and an
HF hydrogen-bonded complex with EOA (P2), (Eqn (2)). For
the first combination, relative energies of the products are near
thermoneutral (Table 5). For the second combination, the sum
of the relative energies of the products is much higher than the
sum of the energies of the reactants and hence it does not
represent the probable combination of products. The relative
energies of the third combination of products show that
the reaction is substantially exothermic (Table 5). In addition,
deprotonation of the MC by ethanolamine was considered but
the relative energies of the incipient anion and protonated
ethanolamine are very endothermic (Table 5). Hence, the
stochiometric equation for the reaction may be written as given
in Eqn (2).
Since the overall order of the reaction is 2; the formation of the
MC must be rate determining and the decomposition of the MC
must be faster than formation. No transition state could be
located for the unimolecular dissociation of MC to form a mixture
of HF and P1, but in the presence of EOA the decomposition takes
place without a forward barrier to form a product complex in
Figure 2. Variation of activation energy in solvents
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Copyright ß 2010 John Wiley & Sons, Ltd.
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INVESTIGATION BY KINETIC MEASUREMENTS
increase in solvent polarity. By comparison, the higher activation
energy determined by both kinetic measurements and DFT
calculations indicate that MNFB is less reactive than DNFB
towards EOA in acetonitrile. This study illustrates that the
mechanism of reaction of ethanolamine with fluoronitroben-
zenes involves the formation of MC and its decomposition is
catalyzed by a second molecule of ethanolamine.
Table 8. The relative energies of the reactants, products,
intermediates, and transition states for the reaction between
MNFB and EOA, in vacuum, and in acetonitrile by MO cal-
culations (kJ/mol)
(
Vacuum)
(Acetonitrile)
B3LYP 6-31G*
Species
B3LYP 6-311G*
MNFB þ 2EOA
MNFB þ EA complex
TS1
0
0
Acknowledgements
ꢀ17.57
ꢀ8.82
67.10
63.71
59.66
42.23
The authors thank Principal, S. H. College, Thevara for providing
infrastructure facilities. The authors also thank Daryl Giblin,
Scientist, Washington University in St. Louis, USA for useful
discussions.
MC
P1 þ P2 complex
ꢀ196.61
ꢀ190.50
Product (P1 þ P2)
ꢀ73.06
ꢀ69.30
the transition state (TS1) decrease when the medium of the
reaction is varied from toluene to acetonitrile, indicating the
effect of solvent polarity on the activation energy of the reaction,
hence increasing reaction rate. This is in agreement with the
experimental observation that the reaction is faster in acetonitrile
than in toluene at the same temperature, Table 4, as well as solvent
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[
[
[1,6]
effects reported.
Furthermore, the energies of the transition
states were calculated in two more solvents, diethylether and
dimethylformamide (DMF). In diethylether, a solvent having
dielectric constant in between that of toluene and ethanol, the
energy of the transition state for the formation of MC is calculated
at 28.9 kJ/mol which is between that for toluene and ethanol.
However, in DMF, a solvent more polar than acetonitrile, the
calculated activation energy is close to that of acetonitrile, 21.9 kJ/
mol (Table 7, Fig. 2). Moreover, measured activation energies for the
reaction in toluene and acetonitrile are 5–6 kJ/mol lower than that
calculated by DFT methods. Nevertheless, the overall similarity
between the experimental and calculated activation energies of the
reaction indicate that the mechanism predicted by theory is
suitable for describing the reaction of EOA with DNFB.
2
[
[
[
[
[
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[
[
[
DFT calculations were repeated for the reaction of MNFB and
ethanolamine in vacuum and in acetonitrile medium. The relative
energy of the transition state for the formation of MC was found
to be 67.1 in vacuum (Table 8) and 59.7 kJ/mol in acetonitrile,
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[
1
0.1039/a902901j
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[
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(
experimental ¼ 62.4 kJ/mol). These results are higher than those
for reaction of EOA with DNFB. Furthermore, the relative energy
of the MC in acetonitrile is less than that in vacuum. Therefore,
ethanolamine reacts with MNFB by a mechanism similar to that
for its reaction with DNFB (Scheme 2). The calculated higher
activation energy of the reaction of MNFB with EOA can be
attributed to the absence of the nitro group at 4-position.
R. Conway, P. J. Rybczynski, K. T. Demarest, Bioorg. Med. Chem. Lett.
2
005, 15, 4790.
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CONCLUSIONS
The rate constants and activation energy values for the reaction
between ethanolamine and 1-fluoro-2,4-dinitrobenzene were
determined by both kinetic measurements and DFT calculations.
The experiments were conducted in acetonitrile and toluene
whereas the calculations were performed in vacuum, toluene,
acetonitrile, and other solvents. The results of both experiment
and DFT calculations show that activation energy decreases with
3
172.
[22] C. J. Cramer, D. G. Truhlar, Acc. Chem. Res. 2008, 41(6), 760–7768.
J. Phys. Org. Chem. 2011, 24 714–719
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