Electrophilicity and nucleophilicity of commonly used aldehydes

Article abstract of DOI:10.1039/c4ob00555d

The present approach for determining the electrophilicity (E) and nucleophilicity (N) of aldehydes includes a kinetic study of KMNO₄ oxidation and NaBH₄ reduction of aldehydes. A transition state analysis of the KMNO₄ promoted aldehyde oxidation reaction has been performed, which shows a very good correlation with experimental results. The validity of the experimental method has been tested using the experimental activation parameters of the two reactions. The utility of the present approach is further demonstrated by the theoretical versus experimental relationship, which provides easy access to E and N values for various aldehydes and offers an at-a-glance assessment of the chemical reactivity of aldehydes in various reactions. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00555d

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Biomolecular Chemistry
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PAPER
Electrophilicity and nucleophilicity of commonly
used aldehydes†
Cite this: Org. Biomol. Chem., 2014,
12, 5781
Sanjay Pratihar
The present approach for determining the electrophilicity (E) and nucleophilicity (N) of aldehydes includes
a kinetic study of KMNO4 oxidation and NaBH4 reduction of aldehydes. A transition state analysis of the
KMNO4 promoted aldehyde oxidation reaction has been performed, which shows a very good correlation
with experimental results. The validity of the experimental method has been tested using the experimental
activation parameters of the two reactions. The utility of the present approach is further demonstrated by
the theoretical versus experimental relationship, which provides easy access to E and N values for various
aldehydes and offers an at-a-glance assessment of the chemical reactivity of aldehydes in various
reactions.
Received 13th March 2014,
Accepted 8th May 2014
DOI: 10.1039/c4ob00555d
www.rsc.org/obc
equation ω = μ2/2η, where μ is the electronic chemical potential
and η is the chemical hardness.7 Later on, Ayers et al. intro-
Introduction
Electrophilicity (E) and nucleophilicity (N) are the two most duced two sets of equations, based on the IP and EA, to
important concepts to help us to rationalize the electronic describe both the electrophilicity and nucleophilicity.8 As an
aspects of reactivity, selectivity, and substituent effects in a important contribution, Gazquez et al. described the electro-
chemical reaction.1 To date, several methods have been donating (ω−) and electroaccepting (ω+) powers using two sets
designed to assess the electrophilicity and nucleophilicity of equations.9 Although some advances have been made in the
scale of molecules using both experimental and theoretical theoretical description of nucleophilicity and electrophilicity,10
tools.2 Mayr et al. successfully evolved the first experimental there exists ample opportunity to expand the experimental
scale for both electrophilicity and nucleophilicity from kinetic determination of the electrophilicity (E) and nucleophilicity
data using the equation log k = s(N + E), in which electrophiles (N) to a wider range of molecules.
are characterized by one parameter (E) and nucleophiles are
During electrophile–nucleophile interactions, an electro-
characterized by two parameters (N, s).3 Alongside this experi- phile (and also a nucleophile) will face both attractive and
mental scale, various theoretical scales have been proposed.4 repulsive forces since molecules contain both electrons and
Following the establishment of Fukui’s frontier molecular nuclei. Depending on the substituent, the predominance of
orbital theory,5 the measure of the electrophilicity was based either electron accepting or donating character will arise
upon the lowest unoccupied molecular orbital (LUMO) eigen- during the interaction process because of the presence of both
value, while the energy of the highest occupied molecular the electrophilic and nucleophilic character in a molecule. So,
orbital (HOMO) characterized the nucleophilicity. However, parameters such as net electrophilicity (the electrophilicity of a
the whole picture became simpler after Koopmans’ theorem, system relative to its own nucleophilicity) or net nucleophili-
in which the energy of the HOMO is approximately equal to city (the nucleophilicity of a system relative to its own electro-
the negative of the ionization potential (IP), and the energy of philicity) are always preferable to determine the actual electron
the LUMO is identified as the negative of the electron affinity accepting or donating character of a molecule.11 A synthetic
(EA).6 Later on, Parr et al. defined electrophilicity as the energy chemist on the bench is often faced with the challenge to tune
of stabilization of a chemical species when it acquires an the reactivity of an aldehyde and deliver the desired selectivity
additional fraction of electronic charge from the environment. in a chemical reaction. For this reason, E and N values would
They described a global electrophilicity index ω by the be useful when selecting an aldehyde in order to fine tune the
selectivity of any chemical transformation of an aldehyde. In
this context, E and N values of a large class of aldehydes have
been evaluated from the rate kinetics of two very simple reac-
tions; the KMnO4 oxidation and NaBH4 reduction of aldehydes
Department of Chemical Sciences, Tezpur University, Napaam, Asaam-784028, India.
E-mail: spratihar@tezu.ernet.in, spratihar29@gmail.com
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
(Fig. 1).
c4ob00555d
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Fig. 1 Electrophilicity (E) and nucleophilicity (N) from the KMnO4 oxi-
dation and NaBH4 reduction of aldehydes.
Results and discussion
In this study, the aldehyde functional group was chosen as a
model system as its reactivity lies between its reduction
product (alcohol) and oxidation product (carboxylic acid) so
that it can gain or lose electrons from a reducing or oxidizing
agent, respectively. In order to determine the nucleophilicity,
the KMnO4 promoted oxidation of various aldehydes was
chosen as a model reaction. The progress of the KMnO4 pro-
moted oxidation of various aldehydes was monitored by
UV-Vis spectroscopy. The progress of the oxidation reaction
was determined from the steady decrease in all four absor-
bance maxima at specific wavelengths (506, 525, 545, and
566 nm) (Fig. 1). All of the kinetic studies of the KMnO4 pro-
moted oxidation reaction of the aldehydes were performed by
monitoring the steady decrease of the absorbance at 545 nm at
different time intervals. The nucleophilicity (N) of a particular
aldehyde was assessed from the pseudo first order rate con-
stant (log k) at 25 °C. Furthermore, to elucidate the mechan-
ism of the oxidation of the aldehyde, Hammett analysis and
activation parameter calculations were also performed.
Hammett analysis of the oxidation reaction led to a small
negative ρ-value (reaction constant = −0.87) (see Fig. S1 in
ESI-1†), which indicates the generation of a small positive
charge at the aldehyde carbon centre in the transition state
(TS).12 The detailed mode of action of potassium permanga-
nate in neutral solution has been studied previously by Wiberg
et al.13 By using isotopic labeling, they showed that the oxidiz-
ing agent appears to be the source of the oxygen introduced
into the aldehyde. Further evidence from their experiments
also suggested that the reaction in neutral solution probably
involves the formation of a permanganate ester of the hydrate
of the aldehyde, followed by a rate-determining loss of the
aldehyde hydrogen. To understand the mechanism of the
KMnO4 oxidation of the aldehydes in neutral solution, and
also to validate the experimentally observed nucleophilicity of
various aldehydes, a transition state (TS) model has been ana-
lyzed (Fig. 2).
Fig. 2 Gibbs free energy profile (in kJ mol−1) for the KMnO4 promoted
oxidation of benzaldehyde to benzoic acid.
between the aldehyde C–H bond and the oxygen center in Int.
would facilitate the transfer of hydrogen towards the oxygen
centre. Therefore, the rate determining step involved the clea-
vage of the aldehyde C–H bond. The overall process involved
the transfer of hydrogen from the aldehyde carbon to oxygen
with the breaking of the O–Mn bond in the transition state
(TS). The optimized transition state and the intermediate geo-
metries, along with some of the important bond lengths for
the KMnO4 promoted oxidation of benzaldehyde, have been
provided in Fig. 2. The relative enthalpies of formation of the
permanganate ester (Int.) intermediates for six para substi-
tuted aldehydes were determined (Fig. 3) using the benz-
Geometries of all TSs and intermediates were optimized
using the Gaussian 03 suite of quantum chemical programs.24
Effective core potentials (ECPs) along with valence basis sets
(LANL2DZ) were used for manganese, while for other atoms a
6-311+G** basis set was used. The nucleophilic attack of
MnO4− on the aldehyde carbon leads to the formation of a per-
manganate ester (Int.) intermediate. Improved proximity
Fig. 3 Relative enthalpies of formation plotted for the permanganate
ester intermediates of six different para substituted aldehydes in the gas
phase and in acetonitrile (in parentheses).
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aldehyde intermediate as a reference (89.6 kJ mol−1 as 0 kJ
mol−1).
The plot shows the facile formation of the permanganate
ester (Int.) intermediate using the electron withdrawing alde-
hyde compared to the electron rich aldehyde because of the
slightly greater positive charge at the aldehyde centre in the
electron withdrawing aldehyde, which will facilitate the attack
−
of MnO4 (Fig. 3). The effect of solvent on the TS and inter-
mediate in the KMnO4 promoted oxidation reaction was
included using a single point energy calculation in a polarized
continuum model (PCM) with acetonitrile as a solvent in same
level of theory.14 Furthermore, to determine the experimental
activation parameters of the oxidation reaction, the reaction
kinetics of the KMnO4 promoted oxidation of five different
para substituted benzaldehydes were studied at six different
temperatures ranging from 2 to 60 °C.15,16 The experimental
enthalpies of formation followed the order Cl < Br < H < OMe
Scheme 1 Equations used to obtain the theoretical N and E values.
ones, which is in agreement with the trend in the nucleophili-
city of the aldehydes, as well as the computed TSs.
<
NMe2, which correlates well with theoretical results
(Table 1).
However, the free energy of activation for the rate determin-
In order to further investigate the relationship between
aldehyde nucleophilicity and its theoretical nucleophilicity
parameter, various aldehydes have been fully optimized
without any symmetry constraints at the B3LYP/6-311+G**
level of theory. Three different methods (MI–MIII) using three
different sets of equations (Scheme 1)8,9 have been utilized to
evaluate theoretical nucleophilicities and electrophilicities. To
check the validity of the observed nucleophilicity data
obtained from the three different methods, para substituted
benzaldehydes were chosen as a test series, and the corres-
ponding calculated N values were plotted against the experi-
ing step is governed by entropy. As is also evident from the
Hammett reaction constants, the generation of a slight positive
charge at the aldehyde carbon in the TS will occur, which will
be stabilized by electron donating substituents. During the
rate determining C–H bond loss, the electron density at the
oxygen centre will determine the transfer of hydrogen and break-
ing of the O–Mn bond. Therefore, one would expect a lower
transition state (TS) barrier in the case of the electron rich
aldehyde, since the electron-donating group could facilitate
the overall bond making and breaking process. The computed
free energy of activation barriers between the intermediates
and TSs of electron rich aldehydes were found to be lower
than those of electron deficient aldehydes (Table 2). The
experimental free energies of activation (ΔG#) at 298 K follow
the order NMe2 < OMe < H < Br < Cl, indicative of a more favor-
able reaction for electron rich aldehydes over electron deficient
mental
N values (Fig. 4). The correlation between the
experimental and calculated N values obtained using Method I
(MI) and II (MII) have been found to be slightly better than
MIII. Further correlation between the theoretical N values versus
Hammett substituent constant (σp) also suggested the superior-
ity of MI and MIII over MII (Fig. 5). The experimental nucleophi-
licity was also studied using various mono, di, and hetero
aldehydes (please see Fig. S5 in ESI-1†).18 The nucleophilicity of
Table 1 Activation parameters for the KMnO4 oxidation of five different
para substituted benzaldehydes
Cl
Br
H
OMe
NMe2
ΔH# (kJ mol−1
ΔS# (J K−1 mol−1
ΔG#298 (kJ mol−1
)
9.1
−276
91.1
9.3
−274
90.9
11.4
−265
90.4
13.6
−254
89.3
20.7
−219
86.1
)
)
Table 2 Computed Gibbs free energies (in kJ mol−1) for important
transition states involved in the KMnO4 oxidation of para substituted
benzaldehydes
NO2
(1)
Cl
(2)
Br
(3)
H
(4)
OMe
(5)
NMe2
(6)
Transition state
ΔG# (kJ mol−1
)
56.8
n.d.
53.2 52.1
38.2 n.d. 31.4 25.7
52.3 52.1
48.0
11.6
ΔG# (kJ mol−1) in
Fig. 4 Plot of theoretical versus experimental nucleophilicity for
various para substituted benzaldehydes obtained using three different
methods.
MeCN
n.d. = not detected.17
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Fig. 6 Plot of the theoretical versus experimental electrophilicities of
various para substituted benzaldehydes obtained using three different
methods.
Fig. 5 Nucleophilicity (N) versus σp plot for different para substituted
benzaldehydes using all three methods.
the aldehydes was studied in acetonitrile solvent using a single
point energy calculation and a PCM model. When the calcu-
lated N values for the aldehydes in acetonitrile were plotted
against the experimental N values, MI was found to be superior
over MII and MIII (Fig. S3 in ESI-1†).
performed at the B3LYP/6-311+G** level of theory. The electro-
philicity of the aldehydes was studied using three methods.
Interestingly, a good correlation was obtained between the
theoretical and experimental electrophilicities of all the ortho,
meta, and para substituted aldehydes (please see Fig. S6 in
ESI-1†). However, in terms of the correlation coefficient
(R2 value), the para substituted benzaldehydes showed better
results than all of the other aldehydes. The plot in Fig. 6 shows
the superiority of MI compared to MIII and MII. Furthermore,
to check the validity of the three methods, calculated E values
of different para substituted benzaldehydes have been plotted
against their corresponding σp value. When judged in terms of
the correlation coefficient (R2 value), MI gave a better corre-
lation between the calculated electrophilicity values versus σp
values than MIII and MII (Fig. 7).
On the other hand, the electrophilicity of an aldehyde is
directly related to its reducing properties. As in the case of the
NaBH4 reduction of aldehydes to alcohols, the reaction rate
directly depends on the ability to accept electrons in the form
of a hydride nucleophile. Therefore, to obtain E values for the
aldehydes, pseudo first order rate constants (k) have been
measured for the NaBH4 reduction of different ortho, meta,
and para substituted benzaldehydes at 25 °C.19 The log(k)
value of the corresponding aldehyde has been assigned as its
electrophilicity. Hammett analysis of the NaBH4 reduction of
aldehydes resulted in a positive ρ-value (reaction constant =
1.58), suggesting a small negative charge in the transition state
(TS).20,23 Furthermore, the activation parameter for the NaBH4
reduction of five different para substituted benzaldehydes has
been determined from the reaction kinetics at 4 different
temperatures, ranging from 2 to 25 °C.21 The activation para-
meters for the NaBH4 reduction have been given in Table 3.
The more positive ΔS# and lower ΔG# values for the electron
deficient aldehydes compared to the electron rich aldehydes
implied the higher reducibility of the former towards NaBH4.
In order to determine the relationship between experimental
electrophilicity and the corresponding calculated electrophili-
city, a computational analysis of various aldehydes has been
Thus, method I (MI) appears to be superior to MII and MIII
for both the E and N value calculations.22 Therefore, MI has
been chosen as a model for further calculation of N and E
Table 3 Activation parameters for the NaBH4 reduction of five different
para substituted benzaldehydes
NMe2
OMe
H
Br
Cl
ΔH# (kJ mol−1
ΔS# (J K−1 mol−1
ΔG#298 (kJ mol−1
)
8.9
−272
90.2
19.9
−219
85.4
16.8
−219
82.2
17.0
−214
80.9
19.6
−204
80.6
Fig. 7 Electrophilicity versus σp plot for different para substituted benz-
aldehydes using all three methods.
)
)
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values for various aldehydes. The two equations,24 derived
from the experimental versus theoretical plots (Fig. 4 and 6)
Theoretical background
were used for the determination of experimental N and E The global reactivity descriptors are defined for the system as a
values for various substituted aldehydes (Table 4).25 The elec- whole. Recently, electrophilicity has been defined by Parr
trophilicity of a molecule dictates its inherent electron accept- et al.7a as the energy of stabilization of a chemical species
ing character. However, there is also an inherent electron when it attains an additional fraction of electronic charge
donating character present in a molecule. During E or N value from the environment. The global electrophilicity index ω is
calculation for a molecule, we often considered only one of the defined as ω = μ2/2η where μ is the electronic chemical poten-
parameters in isolation, which is not the actual E or N of the tial26 and η is the chemical hardness.27 In an important contri-
molecule. Therefore, the net electrophilicity (the electrophili- bution, Gazquez et al.9 have defined the electrodonating power
city of a system relative to its own nucleophilicity) would be a (ω−) as
better descriptor to explain the electrophilic power of an alde-
2
I2
ð3I þ AÞ
hyde. Finally, the net electrophilicity of a particular aldehyde
has been derived from the difference between its E and N
values, which will be very useful to predict the actual electron
withdrawing capacity of the aldehyde. The N, E, and net E
values of various aldehydes are shown in Table 4, which offer
an at-a-glance assessment of the chemical reactivity of various
aldehydes.
ωꢀ
¼
and ωꢀ
¼
ð1Þ
2ðI ꢀ AÞ
16ðI ꢀ AÞ
Note that according to this definition, a smaller value of ω−
signifies a better electron donor. In the present work, nucleo-
philicity has been defined as the inverse of the electrodonating
power (10/ω−) in order to equate with the general notion that
“more is better”. They also defined the electroaccepting power
(ω+) as
2
A2
2ðI ꢀ AÞ
ðI þ 3AÞ
Experimental section
Materials and instruments
ωþ
¼
and ωþ
¼
ð2Þ
16ðI ꢀ AÞ
Double distilled water was used throughout the experiments.
The degassing of oxygen from water and acetonitrile was per-
formed by bubbling argon for 30 minutes. Acetonitrile, the
aldehydes, and KMnO4 were of AR grade. All of the reagents
were used without further purification. All UV-visible absorp-
tion spectra were recorded in a double beam digital spectro-
photometer equipped with a chiller.
Later on, Ayers et al. introduced two sets of equations
derived from the IP and EA for both the electrophilicity and
nucleophilicity as8
2
2
ð3I ꢀ AÞ
ðI þ AÞ
N ¼
and E ¼
ð3Þ
8ðI ꢀ AÞ
8ðI ꢀ AÞ
The electronic chemical potential and the chemical hard-
ness have to be known for the calculation of the electrophili-
city (E) and nucleophilicity (N) index. The electronic chemical
potential is the negative of the electronegativity χ, defined for
an N-electron system with external potential v(r) and total
energy E as the partial derivative of the energy to the number
of electrons at constant external potential and in absence of a
magnetic field:28
UV-vis study for the KMnO4 oxidation of aldehydes
First, an aqueous homogeneous solution of KMnO4 (2 ×
10−4 M) in double distilled oxygen free water was prepared for
the study. Separately, 5 ml of an aldehyde stock solution (2 ×
10−1 M) was prepared in pre-distilled oxygen free acetonitrile.
Then, 200 µL of the aldehyde solution was mixed with a
KMnO4 solution (4 × 10−4 M) in a UV-cuvette and the progress
of the reaction was recorded. The progress of the reaction was
followed by the steady decrease of all four absorbance maxima
at specific wavelengths (506, 525, 545, and 566 nm) (Fig. 1). All
of the rate measurements for the KMnO4 oxidation of the alde-
hydes were performed using a time scan option at a fixed
absorbance (the 545 nm band of KMnO4).
ꢀ
ꢁ
@E
@N
I þ A
μ ¼ ꢀχ ¼
ꢁ ꢀ
ð4Þ
vðrÞ
2
where I and A are the vertical ionization energy and electron
affinity, respectively. These two quantities were calculated in
the Gaussian 03 program29 using the B3LYP methods and the
6-311+G** basis set. Hardness is defined as the corresponding
second derivative as proposed by Parr and Pearson.28
UV-vis study for the NaBH4 reduction of aldehydes
ꢀ
ꢁ
@2E
@N2
For the monitoring of the reduction kinetics of the aldehydes,
an NaBH4 solution (20 M) in double distilled oxygen free water
was prepared. The aqueous NaBH4 solution was admixed with
100 µL of a distilled oxygen free acetonitrile stock solution (2 ×
1
2
η ¼
ꢁ ðI ꢀ AÞ
ð5Þ
vðrÞ
It is now common to exclude the factor 1/2 in the above
10−1 M) of the corresponding aldehyde. All of the rate definition. In this paper we calculated the chemical hardness
measurements for the NaBH4 reduction of the aldehydes were as the difference between the vertical ionization energy I and
performed using a time scan option at a fixed absorbance the electron affinity A, where I = EHOMO = ionization potential
band of a particular aldehyde.
(IP) and A = ELUMO = electron affinity (EA).
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Table 4 Experimental and theoretical nucleophilicity (N), electrophilicity (E), and net E values of various aldehydes from kinetic and theoretical
analysis
Theoreticala
Experimental
Compound
E
Nb
Nc
Ed
1.28
Net E
2-Nitro benzaldehyde
3.76
3.44
3.09
2.99
2.91
2.95
2.93
2.90
2.87
2.85
2.96
2.77
2.77
2.73
2.74
2.77
2.74
2.72
2.72
2.66
2.63
2.61
2.58
2.60
2.60
2.60
2.52
2.46
2.46
2.45
2.53
2.43
2.46
2.46
2.45
2.42
2.40
2.40
2.43
2.33
2.40
2.27
2.40
2.42
2.19
2.29
2.18
2.17
2.23
2.12
2.17
2.17
2.07
2.07
2.05
2.05
2.02
2.08
2.07
2.04
1.87
2.13
2.06
1.97
1.90
1.97
2.00
11.42
11.35
10.96
10.68
10.67
10.41
10.41
10.53
10.62
10.58
9.97
10.62
10.52
10.61
10.51
10.30
10.28
10.35
10.29
10.14
9.90
10.02
10.15
9.89
9.87
9.78
9.64
9.95
9.89
9.91
9.48
9.98
9.78
9.82
9.83
9.78
9.87
9.86
9.61
9.57
9.07
9.76
9.06
8.97
9.53
8.90
9.39
9.38
8.97
9.33
9.03
8.97
9.30
9.28
9.26
9.23
9.33
8.66
8.74
8.72
9.54
8.10
8.43
8.90
9.14
8.50
8.23
−3.80
−3.78
−3.63
−3.53
−3.53
−3.43
−3.43
−3.47
−3.51
−3.49
−3.27
−3.51
−3.47
−3.51
−3.47
−3.39
−3.39
−3.41
−3.39
−3.33
−3.24
−3.29
−3.34
−3.24
−3.24
−3.20
−3.15
−3.26
−3.24
−3.25
−3.09
−3.27
−3.20
−3.21
−3.22
−3.20
−3.24
−3.23
−3.14
−3.13
−2.94
−3.19
−2.94
−2.91
−3.11
−2.88
−3.06
−3.05
−2.90
−3.04
−2.93
−2.91
−3.02
−3.02
−3.01
−3.00
−3.04
−2.79
−2.82
−2.81
−3.11
−2.59
−2.71
−2.88
−2.97
−2.73
−2.63
5.09
4.45
3.64
3.33
3.18
3.17
3.12
3.10
3.08
3.03
3.02
2.90
2.85
2.82
2.79
2.78
2.72
2.70
2.67
2.51
2.36
2.36
2.35
2.31
2.29
2.25
2.05
2.05
2.03
2.02
2.01
2.01
2.00
2.00
1.99
1.92
1.91
1.90
1.86
1.67
1.62
1.62
1.61
1.61
1.38
1.34
1.31
1.28
1.25
1.17
1.16
1.14
1.07
1.05
1.02
1.00
0.97
0.86
0.85
0.79
0.77
0.74
0.72
0.72
0.68
0.58
0.53
3-Nitro benzaldehyde
0.67
0.01
4-Cyano benzaldehyde
4-Chloroisophthalaldehyde
2-Formyl benzonitrile
−0.20
−0.35
−0.26
−0.31
−0.37
−0.43
−0.46
−0.25
−0.61
−0.62
−0.69
−0.68
−0.62
−0.67
−0.72
−0.72
−0.82
−0.88
−0.93
−0.99
−0.93
−0.95
−0.95
−1.10
−1.22
−1.21
−1.23
−1.08
−1.26
−1.20
−1.22
−1.23
−1.28
−1.33
−1.33
−1.27
−1.46
−1.32
−1.57
−1.33
−1.30
−1.73
−1.54
−1.75
−1.77
−1.65
−1.87
−1.76
−1.76
−1.96
−1.97
−1.99
−2.00
−2.07
−1.93
−1.97
−2.02
−2.34
−1.85
−1.99
−2.16
−2.29
−2.15
−2.10
Phthalaldehyde
4-Acetyl benzaldehyde
4-Formyl benzoic acid
3,4-Dichloropicolinaldehyde
Ethylglyoxalate
5-Nitro-1H-indole-3-carbaldehyde
3-Formyl benzonitrile
4-Trifluoromethyl benzaldehyde
4-Nitro benzaldehyde
2,4,5-Trifluorobenzaldehyde
4-Chloronicotinaldehyde
Methyl-4-formylbenzoate
4-Chloropicolinaldehyde
Isophthalaldehyde
2,3-Dichlorobenzaldehyde
4-Chlorofuran-2-carbaldehyde
3-Acetyl benzaldehyde
3-Formyl benzoic acid
2,6-Dichlorobenzaldehyde
2-Formyl benzoic acid
3-Phenyl propynal
2-Acetyl benzaldehyde
Methyl-3-formylbenzoate
3-Chloro benzaldehyde
2-Chloro aldehyde
Cinnamaldehyde
3-Fluoro benzaldehyde
3-Bromo benzaldehyde
2-Bromo benzaldehyde
Picolinaldehyde
4-Bromo benzaldehyde
2-Fluoro benzaldehyde
4-Chloro benzaldehyde
Methyl-2-formylbenzoate
Thiophene-2-carbaldehyde
Biphenyl-4-carbaldehyde
4-Fluoro benzaldehyde
Biphenyl-2-carbaldehyde
2-(Thiophen-3-yl) benzaldehyde
Benzaldehyde
2-Naphthaldehyde
2-Methyl benzaldehyde
Furan-2-carbaldehyde
2-Chloro-3,4-dihydroxybenzaldehyde
3-Methyl benzaldehyde
3-Hydroxy benzaldehyde
4-Tert-butyl-2-hydroxybenzaldehyde
4-Methyl benzaldehyde
4-Ethyl benzaldehyde
4-Propyl benzaldehyde
4-Formylphenylboronic acid
Thiophene-3-carbaldehyde
3-Chloro-4-hydroxy-5-methoxybenzaldehyde
3-Methoxy benzaldehyde
2-Methoxy benzaldehyde
Formaldehyde
2-(Naphthalen-2-yl)benzaldehyde
4-Mercapto benzaldehyde
4-Hydroxy benzaldehyde
Furan-3-carbaldehyde
3,4-Dihydroxybenzaldehyde
3-Amino benzaldehyde
5786 | Org. Biomol. Chem., 2014, 12, 5781–5788
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Table 4 (Contd.)
Theoreticala
Experimental
Compound
E
Nb
8.25
Nc
Ed
Net E
3,4,5-Trimethoxybenzaldehyde
4-Methoxy benzaldehyde
5-Chloro-1H-indole-3-carbaldehyde
4-Hydroxy-3-methoxybenzaldehyde
3-(Dimethylamino) benzaldehyde
Phenyl acetaldehyde
4-Amino benzaldehyde
Acetaldehyde
3-Phenyl propanal
2-(Dimethylamino) benzaldehyde
Heptanal
1.97
1.88
1.87
1.86
1.86
1.64
1.71
1.54
1.55
1.73
1.46
1.55
−2.64
−2.78
−2.72
−2.62
−2.42
−2.83
−2.55
−2.87
−2.75
−2.39
−2.79
−2.33
−2.14
−2.33
−2.34
−2.36
−2.36
−2.79
−2.65
−2.98
−2.95
−2.61
−3.13
−2.95
0.50
0.45
0.37
0.26
0.05
8.63
8.46
8.20
7.63
8.77
7.99
8.88
8.56
7.57
8.65
7.40
0.04
−0.11
−0.11
−0.20
−0.22
−0.34
−0.62
4-(Dimethylamino) benzaldehyde
a Theoretical calculation performed at the B3LYP/6-311+G** level of theory in the gas phase. b The more positive N value indicates less electron
donating ability. c For nucleophilicity (N), N (Theo.) = −2.73 × N (Exp.) + 1.04 has been used. d For electrophilicity (E), E (Theo.) = 0.52 × E (Exp.) +
3.09 has been used.
New York, 2001; (b) M. B. Smith and J. March, in Advanced
Organic Chemistry: Reactions, Mechanisms, and Structure,
Conclusions
In summary, the nucleophilicity (N) and electrophilicity (E) of
various aldehydes have been determined from the kinetics of
two simple reactions; namely, the KMnO4 oxidation and
NaBH4 reduction reactions of aldehydes. The validity of the
experimental method has been checked using the activation
parameters of the two reactions. The mechanism of the
KMnO4 oxidation of the aldehydes has been studied with the
help of transition state analysis. Furthermore, theoretical N
and E values of various aldehydes have been calculated at the
B3LYP/6-311+G** level of theory with three different equations.
The validity of the methods was evaluated from the linear
relationship between the experimental versus theoretical plots,
and theoretical versus σp plots for different para substituted
benzaldehydes. Finally, N, E, and net E values for a variety of
aldehydes have been evaluated, which offer an at-a-glance
assessment of the chemical reactivity of various aldehydes.
The concept can be applied further to determine the nucleo-
philic and electrophilic power of molecules like ketones and
alkenes etc., with reactivities that lie between their oxidation
and reduction products.
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Acknowledgements
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Financial support of this work by DST-New Delhi (to SP for
INSPIRE fellowship and research grant) is gratefully acknowl-
edged. SP is highly grateful to Professor M. K. Chaudhuri for
all the help and support. I fondly dedicate this work to
Prof. Pratim Kumar Chattaraj, who is as constant a source of
inspiration as one could ever imagine.
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Notes and references
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2010, 75, 4957; (c) F. De Vleeschouwer, V. Van Speybroeck, 23 Both E and N values of all the aldehydes have been calcu-
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E values are given in Table S8 in ESI-1†
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N (Theo.) = −2.73 × N (Exp.) + 1.04 from the
theoretical versus experimental plots have been utilized
for the calculation of N, E and net E values for the
aldehydes.
12 F. C. Tompki, Trans. Faraday Soc., 1943, 39, 280.
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Mayr et al. Please see Fig. S7 and Table S9 in ESI-1†;
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14 J. Tomasi and M. Persico, Chem. Rev., 1994, 94, 2027.
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27 R. G. Parr and R. G. Pearson, J. Am. Chem. Soc., 1983, 105,
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17 The ΔG# values for NO2 and Br substituted aldehydes 28 R. G. Parr, R. A. Donnelly, M. Levy and W. E. Palke, J. Chem.
in MeCN are high and do not follow the usual gas phase
Phys., 1978, 68, 3801–3807.
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18 However, in terms of the correlation coefficient, the plot
between the experimental and theoretical nucleophilicities
of mono, di, and hetero aldehydes combined is slightly
poorer compared to para substituted aldehydes (please see
Fig. S6 in ESI-1†). The author thanks the esteemed reviewer
for raising this point.
19 For the NaBH4 reduction please see: (a) S. W. Chaikin and
W. G. Brown, J. Am. Chem. Soc., 1949, 71, 122;
(b) G. W. Gribble, Chem. Soc. Rev., 1998, 27, 395; and refer-
ences therein.
20 Please see Fig. S2 in ESI-1†
21 The reduction reaction kinetics of aldehydes beyond the
range of 2 to 25 °C is not possible because of the solvent
system and decomposition behavior of NaBH4 at higher
temperatures.
22 It should be noted that while Method I (MI) has been suc-
cessfully utilized for this set of molecules, providing good
correlation between the experimental and computed
results, other methods can also be equally useful to ration-
alize the reactivity for other sets of molecules.
5788 | Org. Biomol. Chem., 2014, 12, 5781–5788
This journal is © The Royal Society of Chemistry 2014