A quantitative structure-reactivity assessment of phenols by investigation of rapid iodination kinetics using hydrodynamic voltammetry: Applicability of the Hammett equation in aqueous medium

Article abstract of DOI:10.1002/kin.20801

Halogenations of aromatic substrates in aqueous medium are essentially electrophilic substitutions proceeding at rates concomitant with the nature of the substrates and substituent motifs. Kinetics as an investigatory tool for the quantitative assessment of the structure-reactivity correlation in these reactions for a diverse range of substrates has rarely been reported, presumably due to the rapidity of these reactions in aqueous medium. We have used hydrodynamic voltammetry to investigate the rapid kinetics of uncatalyzed iodination of phenol and eight substituted phenols by iodine monochloride at constant pH in aqueous medium. The Arrhenius plots for these reactions yield comprehensive kinetic and thermodynamic data. The quantitative structure-reactivity correlation stemming from the regio- and stereospecificity of the substituent motifs on the substrates has been examined through the Hammett plot, which shows a negative slope of 1.87. The magnitudes of the rate constants, energies of activation, frequency factors, and entropy change obtained for the nine fast reactions reported, reflect the relative ease of the reaction dynamics in quantitative terms thereby ascertaining the relative reactivities of the phenols studied herein.

Full text of DOI:10.1002/kin.20801

A Quantitative
Structure–Reactivity
Assessment of Phenols
by Investigation of Rapid
Iodination Kinetics Using
Hydrodynamic
Voltammetry: Applicability
of the Hammett Equation
in Aqueous Medium
VITTHAL T. BORKAR, SHANTARAM L. BONDE, VIJAY T. DANGAT
Department of Chemistry, Nowrosjee Wadia College Research Centre, Pune 411001, India
Received 13 November 2012; revised 21 February 2013; accepted 18 April 2013
DOI 10.1002/kin.20801
Published online 23 August 2013 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: Halogenations of aromatic substrates in aqueous medium are essentially elec-
trophilic substitutions proceeding at rates concomitant with the nature of the substrates and
substituent motifs. Kinetics as an investigatory tool for the quantitative assessment of the
structure–reactivity correlation in these reactions for a diverse range of substrates has rarely
been reported, presumably due to the rapidity of these reactions in aqueous medium. We have
used hydrodynamic voltammetry to investigate the rapid kinetics of uncatalyzed iodination
of phenol and eight substituted phenols by iodine monochloride at constant pH in aqueous
medium. The Arrhenius plots for these reactions yield comprehensive kinetic and thermody-
namic data. The quantitative structure–reactivity correlation stemming from the regio- and
Correspondence to: Vijay T. Dangat; e-mail: vijaydangat@
gmail.com.
This paper is dedicated to Professor Dr. T. S. Rao on the occasion
of his 82nd birthday, in recognition of his outstanding contributions
to chemical kinetics, especially rapid kinetics in aqueous medium.
C
ꢀ
2013 Wiley Periodicals, Inc.

694
BORKAR, BONDE, AND DANGAT
stereospecificity of the substituent motifs on the substrates has been examined through the
Hammett plot, which shows a negative slope of 1.87. The magnitudes of the rate constants,
energies of activation, frequency factors, and entropy change obtained for the nine fast reac-
tions reported, reflect the relative ease of the reaction dynamics in quantitative terms thereby
ascertaining the relative reactivities of the phenols studied herein. ꢀC 2013 Wiley Periodicals,
Inc. Int J Chem Kinet 45: 693–702, 2013
of phenol and eight substituted phenols in iodination re-
actions under uniform conditions, by following the fast
kinetics, in aqueous medium. These reactions typify
electrophilic aromatic substitutions. We have carried
out these reactions without using any catalyst. Con-
stant relative proportions of the phenol–phenolate con-
centrations were ensured by maintaining a pH value of
4.8. Iodine monochloride (ICl) being a polar molecule
facilitates the electrophilic attack on the substrates in
contrast to the nonpolar iodine molecule. Hence, the
reactions under study are remarkably rapid. The use
of ICl also minimized the possibility of formation of
the tri-iodide anion in these electrophilic substitution
reactions besides not being a controversial halogenat-
ing species like the protonated hypohalous acid [18].
All the reactions studied herein were found to have
half-lives of barely a few seconds. However, these re-
actions being of the second order, their half-lives were
extended by diluting the solutions whereby convenient
kinetic measurements became feasible using hydro-
dynamic voltammetry. The rate of disappearance of
ICl, the only electroreducible species among the re-
actants and products, was measured at a rotating plat-
inum microcathode by the hydrodynamic voltamme-
try technique. These kinetic investigations confirmed
the relative ease of the reaction dynamics speculated
on the basis of the substrate structures in these halo-
genations. Comprehensive kinetic and related thermo-
dynamic data for the iodination of the regioisomers of
cresols, nitrophenols, and chlorophenols were obtained
and compared with those for phenol. The analysis of
the product by the standard technique [19] in each of
these nine reactions revealed the regiospecific forma-
tion of the monoiodo isomer in these reactions, which
was also confirmed from NMR spectra.
INTRODUCTION
Halogenated aromatic compounds are important in
synthetic organic chemistry [1] as key intermediates
used in the preparation of organometallic reagents [2,3]
and as significant entities in coupling reactions such
as Negishi cross-coupling involving transition met-
als [4]. The halogen functionality accounts for the
use of these compounds as medicinal molecules [5–7],
herbicides, pesticides, fire retardants, and other com-
mercially valuable products. Halogenations of aro-
matic substrates are known to be electrophilic aro-
matic substitution reactions [8]. Iodination of aromatic
rings has important applications in synthesizing natu-
ral products and pharmaceuticals [9–11]; 4-iodophenol
is known to function as an enhancer in horseradish
peroxidase–catalyzed luminal chemiluminescence in
liposomes [12]. Iodoarene intermediates are used in the
synthesis of useful drugs [13]. Therefore, it has always
remained the endeavor of chemists to elucidate plausi-
ble mechanistic routes for these reactions in terms of
substrate reactivity. These being electrophilic substitu-
tion reactions, the rates depend on the electrophilic-
ity of the reagent, nucleophilicity of the substrate,
and steric compulsions of both. The regiospecificity
and nature of the substituent motif on the substrate
scaffold coupled with its stereoplanarity operate in
unison to determine the substrate reactivity. In aque-
ous medium, these reactions are rapid and measure-
ments of their rates necessitate special techniques to
quantitatively ascertain the reactivity to seek justifica-
tion of the speculated mechanistic routes involved. A
search through the literature reveals the paucity of such
quantitative investigations contrary to reports in non-
aqueous solutions. Berliner has studied the iodinations
of chlorophenol and anisole in acidic solutions [14],
whereas Grovenstein and Aprahamain have reported
those of dibromo phenols [15]. Schutte and Havinga
have studied the base catalysis for the iodination of
imidazole and p-cresol [16]. Vibhute and Khansole
have reported the slow first-order kinetics of iodina-
tion of substituted phenols by pyridinium iodochloride
in methanol [17].
Under these conditions, the reaction rates solely
depended on the nucleophilicity of the substrate, re-
giospecificity of the substituent, and electrophilicity
of the reagent. Consequently, the reaction rates deter-
mined are rational indicators of the ease of the plausible
mechanistic route considering the substrate structures.
The substrate reactivities are determined in quantita-
tive terms from the comprehensive kinetic and relevant
thermodynamic data obtained. A Hammett plot [20,21]
has been attempted to quantitatively correlate structure
In contrast to these investigations, we have at-
tempted a comprehensive assessment of the reactivity
International Journal of Chemical Kinetics DOI 10.1002/kin.20801

QUANTITATIVE STRUCTURE–REACTIVITY ASSESSMENT OF PHENOLS
695
Table I Calibration of the Diffusion Current of ICl at
Various Temperatures for the Uncatalyzed Iodination of
Phenol in Aqueous Medium at pH 4.8 ( 0.2 nA Error)
and reactivity of the substrates, in view of the dearth
of such reports in aqueous medium for the reactions
under study.
Microgram quantities of chemicals required in this
study, their nonhazardous nature, and very short reac-
tion times of the reactions under study are factors that
adhere to green chemistry principles.
Diffusion Current (nA)
[ICl]
(× 10−6 M) 10.0◦C 15.0◦C 20.0◦C 25.0◦C 30.0◦C
1.0
2.0
3.0
4.0
5.0
7.7
15.5
23.2
31.0
38.0
8.2
16.1
24.8
32.2
41.5
8.5
17.0
25.6
34.1
42.3
9.0
18.1
27.1
36.5
44.6
9.4
18.8
27.8
38.0
46.9
EXPERIMENTAL
General
Potential applied at the RPE versus SCE is 0.1 V.
All chemicals were purchased from commercial
sources and used as supplied. Stock solutions of AR
grade 0.001 M ICl, phenol, o-cresol, m-cresol, p-cresol,
o-chlorophenol, m-chlorophenol, p-chlorophenol, m-
nitrophenol, p-nitrophenol, and the supporting elec-
trolyte 0.1 M potassium chloride were prepared in
double-distilled water. Sodium citrate and citric acid,
each 0.1 M, were prepared for the buffer system. Io-
dine monochloride solution of the required concentra-
tion was prepared after determining the exact strength
of the stock solution by iodometric titration.
buffer components required for pH 4.8. The shunt was
adjusted for the deflection of the galvanometer light
spot to be within scale limits. 1.0 cm galvanometer
light spot deflection on the scale corresponded to a dif-
fusion current value of 1.0 nA. The shunt value was
kept constant for all the temperatures studied for the
reaction. All the calibration readings were carried out
only after the solutions attained the thermostat temper-
atures at which the kinetic readings were subsequently
to be observed. The diffusion current values, in terms
of the deflection of the light spot on the scale, were
recorded for various ICl concentrations in the range of
1 × 10−6 to 5 × 10−6 M. The plots of diffusion current
in nanoampere versus the concentration of ICl for dif-
ferent temperatures are linear as shown in Table I and
Fig. 1. Calibration for the other eight compounds was
similarly carried out using the appropriate concentra-
tion range of ICl.
Kinetic Measurements Using
Hydrodynamic Voltammetry
The rotating platinum electrode (RPE) was an inverted
“T”-shaped glass tube 30 cm long and 5 mm in di-
ameter, containing mercury. A platinum wire of length
1 cm and diameter 1 mm was fused at the tip of the
glass tube such that 0.5 cm of it protruded out. A cop-
per wire was dipped in the glass tube containing mer-
cury for electrical contact. The electrode assembly was
mounted on a pair of pulleys and rotated at 600 rpm
by a synchronous motor. The inverted “T” shape of
the glass tube, to which the platinum electrode was
fused, facilitated stirring of the reaction mixture while
rotating.
Kinetic Measurements of Iodination of Phenol. The
reactants, ICl and phenol, underwent double dilution
The saturated calomel electrode (SCE) is the posi-
tive electrode, which is the reference electrode.
Calibration of Diffusion Current. The iodination of
phenol, among the reactions studied, is described. The
RPE and SCE were dipped in 50.0 cm3 of 5 × 10−4 M
potassium chloride, the supporting electrolyte contain-
ing the required buffer solutions. A potential of +0.1 V
versus the SCE was applied at the RPE by means of
a potentiometric arrangement. The galvanometer light
spot was ensured to show zero deflection on the scale.
The supporting electrolyte solution was then replaced
by 5 × 10−6 M 50.0 cm3 ICl solution containing 5 ×
10−4 M potassium chloride and the amount of the
Figure 1 Calibration of the diffusion current of ICl at vari-
ous temperatures for the uncatalyzed iodination of phenol in
aqueous medium at pH 4.8.
International Journal of Chemical Kinetics DOI 10.1002/kin.20801

696
BORKAR, BONDE, AND DANGAT
Table II Kinetics of Uncatalyzed Iodination of Phenol
at 25.0◦C by ICl in Aqueous Medium at pH 4.8 ( 0.2 nA
Error)
Diffusion
Current (nA)
[ICl]
[ICl]−1
Time (s)
(× 10−6 M)
(× 105 M−1
)
20
30
40
50
60
70
34.5
30.0
27.5
25.0
22.5
22.0
3.85
3.45
3.08
2.82
2.63
2.39
2.60
2.90
3.25
3.55
3.80
4.20
Table III Constant Parameters in the Kinetics of
Uncatalyzed Iodination of Phenol in Aqueous Medium
at All Temperatures at pH 4.8
Parameter
Value
Potential applied at the RPE versus SCE
0.1 V
Figure 2 Kinetics of the uncatalyzed iodination of phenol
by ICl in aqueous medium at various temperatures at pH 4.8.
Initial concentration of iodine monochloride 5 × 10−6
M
M
M
Initial concentration of phenol
5 × 10−6
Ionic strength of the reaction medium
Concentration of potassium chloride
Concentration of sodium citrate
Concentration of citric acid
2.55 × 10−2
5 × 10−4
0.0125 M
0.0125 M
50.0 cm3
M
rate constant k2 of the iodination reaction under study
(Fig. 2).
The kinetic runs for the other eight reactions were
similarly carried out using appropriate initial reactant
concentrations, which facilitated recording of the dif-
fusion current at quick but convenient intervals of time.
Total volume of the reaction mixture
after mixing to a total volume of 50 cm3. Hence, ad-
ditions of the reactants were made in the following
manner: 25 cm3 of 10 × 10−6 M ICl containing 5 ×
10−4 M potassium chloride and the required buffer
components were kept in a flask and maintained at the
desired temperature in a thermostat. In another flask,
25 cm3 of 10 × 10−6 M phenol containing 5 × 10−4 M
potassium chloride and the required buffer components
were maintained in the same thermostat. After the ther-
mostat temperature was attained by all the solutions,
the two reactant solutions were simultaneously added
to the reaction vessel kept in the thermostat in which
the RPE was rotating and SCE was dipped. The time
at the moment of mixing was noted in a stop clock
that was already started, and the decaying diffusion
current due to the unreacted ICl was recorded at every
ten seconds in terms of the galvanometer light spot on
the scale until about one half-life of the reaction under
study was completed (Table II). The final initial con-
centrations of the reactants due to dilution to 50 cm3
of the reaction mixture are indicated (Table III).
Experimental Errors. The above procedure of cali-
bration and kinetic measurements was repeated thrice
for checking the reproducibility of the galvanometer
measurements, which were found to be within the lim-
its of 0.2 nA error. The galvanometer sensitivity and
response time were such that the error in the deter-
mination of the decaying nanocurrents due to iodine
monochloride in these studies was ≤1%.
The error in preparing standard stock solutions of
the reactants due to weighing error was ≤0.25% con-
sidering the sensitivity of the balance used.
The overall experimental error in view of the above
in determining Ea and ꢀS= was ≤2%.
RESULTS AND DISCUSSION
Optimization of the Reaction Conditions
To assess the relative reactivity of the substrates, opti-
mization of the reaction conditions was essential. Iod-
inations are the slowest among halogenations but be-
come remarkably rapid when the reagent is dipolar like
ICl in contrast to molecular iodine. We have chosen ICl
because of its superior potential as an electrophile. The
relatively more reactive species between phenol and
From the calibration plot at the relevant temper-
ature, the unreacted concentrations of ICl at various
instants of time were evaluated in the kinetic run. The
reaction was of the second order, and equal concen-
trations of the reactants were used hence the plot of
[ICl]−1 versus time was linear, the slope which was the
International Journal of Chemical Kinetics DOI 10.1002/kin.20801

QUANTITATIVE STRUCTURE–REACTIVITY ASSESSMENT OF PHENOLS
697
Table IV Variation of the Specific Reaction Rate of
Iodination of Phenol by ICl in Aqueous Medium with
Temperature at pH 4.8 (≤2%)
phenolate anion in these aromatic electrophilic substi-
tution reactions is the phenolate anion; hence constant
relative proportions of the phenol–phenolate concen-
trations have been ensured by maintaining a constant
pH value of 4.8 throughout these studies. The citric
acid–sodium citrate buffer system is preferred as it is
not known to react with aqueous ICl as is the case with
other buffer systems.
The hydrodynamic voltammetry technique was em-
ployed to measure the diffusion-limited current due to
ICl at a rotating platinum cathode in these rapid re-
actions. This technique necessitated the use of a large
concentration of a supporting electrolyte. Potassium
chloride was chosen for this purpose, which also sup-
pressed the possible hydrolysis of ICl, due to the com-
mon ion effect, according to the equilibrium [22]
[T]−1
Temperature (K) (× 10−3 K−1
)
k2 (M−1 s−1
)
log k2
283
288
293
298
303
3.53
3.47
3.41
3.36
3.30
2060
3570
3160
3980
4790
3.31
3.41
3.50
3.60
3.68
ICl + H2O ꢀ IOH + HCl
The ionic strength is maintained constant in the study.
Under these conditions, the dipolar ICl molecule
was the sole iodinating species in the reactions studied.
The kinetic and related thermodynamic data obtained
have been interpreted on the principles of stereochem-
istry and electrophilic substitution.
Thermodynamic and Kinetic Analyses
Figure 3 Variation of the specific reaction rate of iodination
of phenol by ICl in aqueous medium at different temperatures
at pH 4.8.
The kinetics of iodination of phenol, cresols, and the
regioisomers of chlorophenol and nitrophenol ICl was
studied using the platinum microelectrode (RPE) ro-
tated at 600 rpm by an ac electric motor. A poten-
tial of 0.1 V versus a SCE was applied at the RPE.
The diffusion-limited current due to unreacted ICl was
recorded at every 10 s from the start of the reaction,
using a moving coil mirror galvanometer of 1 nA cm−1
sensitivity. The galvanometer readings were separately
calibrated over a range of ICl concentrations at the
temperatures at which the kinetic measurements were
to be carried out. From these, the concentrations of
unreacted ICl in the reaction at various instants were
determined. The kinetic measurements for each reac-
tion were carried out at five different temperatures to
determine the energy of activation, as shown in Table
IV (see Fig. 3). The specific reaction rates determined
were found to be reproducible to within 2% consid-
ering the various sources of errors. Appropriate initial
concentrations of the reactants that facilitated conve-
nient kinetic measurements were used in each reaction.
The values of energy of activation, frequency factor,
and entropy change for each of the nine reactions stud-
ied, were evaluated.
were examined to study the structure–reactivity cor-
relation of these substrates on a quantitative scaffold.
A summary of the kinetic and related thermodynamic
data for the reactions studied is presented in Table V.
Quantitative Determination of the
Reactivity Order of Cresols, Chlorophenols,
and Nitrophenols
The study ascertained the order of reactivity for the
uncatalyzed iodination of phenol and regioisomers
of cresol, chlorophenol, and nitrophenol in aqueous
medium in quantitative terms. The second-order rate
constants k2 were determined using hydrodynamic
voltammetry by monitoring the diffusion-limited cur-
rent due to ICl at a rotating platinum cathode. Under
the conditions in this study, the ICl molecule was the
sole iodinating species in all the reactions studied. The
kinetic and related thermodynamic data obtained under
these conditions have been interpreted on the principles
of stereochemistry and electrophilic substitution.
The kinetic and thermodynamic data obtained for
the iodination of phenol and eight phenol derivatives
International Journal of Chemical Kinetics DOI 10.1002/kin.20801

698
BORKAR, BONDE, AND DANGAT
Table V Quantitative Summary of the Rapid Kinetics of Uncatalyzed Iodination of Phenols in Aqueous Medium at pH
4.8 Using ICl
k2 at 25◦C
Initial Reactant
Ea
Frequency Factor,
ꢀS=
Substrate
(M−1 s−1
)
t1/2 at 250 (s) Concentration (× 10−5 M) (kJ mol−1
)
A (× 108 M−1 s−1
)
(J K mol−1
)
o-Cresol
m- Cresol
p- Cresol
Phenol
o-Chlorophenol
m-Chlorophenol
p-Chlorophenol
m-Nitrophenol
p-Nitrophenol
167
6250
398
3162
164
1698
355
6
60
32
50
63
61
59
56
33
59
10.0
0.50
5.0
0.50
10.0
1.0
5.0
500.0
100.0
45.0
28.7
40.0
32.4
41.7
35.0
43.5
60.0
54.0
129.0
6.7
36.7
7.7
33.3
−59.7
−84.3
−70.1
−77.5
−70.9
−73.9
−58.4
−37.0
−48.4
45.4
149.0
1970.0
494.0
17
Typical Calculations. Iodination of phenol by ICl
Interpretation of Kinetic and
Thermodynamic Data
(i) Specific Reaction Rate, k. The graph of [ICl]−1
versus time is a straight line at all temperatures
for both the reactions; hence both the reactions
follow the second-order kinetics and the specific
reaction rates are the slopes of these lines.
(ii) Energy of activation, Ea
The kinetic and related thermodynamic data obtained
under these uniform conditions have been interpreted
on the basis of the principles of stereochemistry and
electrophilic substitution. Cresols showed the highest
reactivity toward iodination followed by chlorophe-
nols. Nitrophenols showed relatively the lowest reac-
tivity among the three groups of the phenol derivatives
studied.
The –OH group in cresols is ortho and para directing
in electrophilic substitutions, whereas the –CH3 group
is ortho directing. Both these effects operate in unison
in m-cresol, which indeed are confirmed from the high-
est rate of iodination observed for this compound. The
other two cresols manifest relatively lower reactivity
in terms of the rates of iodination due to the lack of this
additive activation effect of the two substituent groups.
There is steric congestion of the hydroxyl and methyl
groups in o-cresol, resulting in the lack of coplanarity
of the benzene ring with one of these substituents. This
causes deteriorated aromaticity of the substrate, man-
ifested from the lowest specific reaction rate for the
iodination of o-cresol among the three regioisomers
(see Table V).
Ea = −2.303 × R × slope of the plot log k V sT −1
= −2.303 × 8.314 × (−1692.16)
= 32.4 kJ mol−1
(iii) Preexponential or frequency factor, A
Iodination of phenol by ICl
k = A exp ( − Ea/RT )
log A = log k + Ea/2.303 RT
A = 7.7 × 108 M−1s−1
(iv) Entropy of activation , ꢀS=
The –Cl group is electron withdrawing due to the
inductive effect and also electron donating due to the
electron rich nature of the halogen atom. However,
halogens show a stronger mesomeric effect than in-
ductive. Thus the reactivity order of the three regioi-
somers of chlorophenol is similar to that of cresols
albeit the rates for iodination are slower than those
of cresols. The nitro group is plainly electron with-
drawing unlike the halo group. This is clearly ev-
ident from the lowest specific reaction rate for the
iodination of m-nitrophenol among all the substrates
studies.
ꢀS= = 2.303R log k − 2.303 R log (ek∗T /h)
+ Ea/T
ꢀS= = 19.15 log k − 253.25 + Ea/T
ꢀS= = −77.5 JK−1mol−1
where e = 2.713, h = Planck constant, and k* = Boltz-
mann constant.
Similar mathematics for the calculation of k, Ea, A,
and ꢀS= for the other eight substrates was adopted.
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QUANTITATIVE STRUCTURE–REACTIVITY ASSESSMENT OF PHENOLS
699
Table VI Hammett Constants for the Substituents and Reactions Studied and Their Correlation with the Rate
Constants Observed at 25.0◦C (≤2%)
Compound
k2 (M−1 s−1
)
log k2
pKa
σ
ꢀS= (J K−1 mol−1
)
x
Phenol
m-Cresol
p-Cresol
m-Chlorophenol
p-Chlorophenol
m-Nitrophenol
p-Nitrophenol
3162
6250
398
1698
355
6
3.5000
3.7959
2.6000
3.2300
2.5502
0.7782
1.2304
9.94
10.08
10.19
9.02
9.38
8.35
0.00
−0.14
−0.25
0.92
0.56
0.75
−77.52
−84.25
−70.11
−73.94
−58.44
−37.00
−48.48
17
7.14
1.23
the pKa or pKb value of the acid or base from which
the substrate is derived. If the substituent has no effect,
σ is zero. If the substituent is electron withdrawing, σ
is positive and if the substituent is electron donating it
is σ negative.
Applicability of the Hammett Equation
to the Data in the Study
A correlation between the structure of a molecule and
its chemical reactivity is a challenging feature of phys-
ical organic chemistry, and quantification of such a
correlation is even more intriguing. The structure of a
molecule is an intrinsic property and is independent of
the solvent effect. However, the experimentally mea-
sured observable, the reaction rate, is affected by the
nature of the solvent. The structure of a molecule deter-
mines its physical properties, chemical reactivity, and
consequently its biological activity. Speculations on
the reactivity of molecules from their structures can-
not be generalized since correlation between chemical
reactivity and structure cannot be deduced from any
known laws but depends on several factors that have
to be experimentally verified. The Hammett equation
nonetheless is a rational indicator of the structure and
reactivity on a quantitative scaffold.
A fit of the Hammett equation to the data in the
study has been attempted to further elucidate the
structure–reactivity correlation in the reactions studied
(Table VI).
Hammett has summarized quantitatively the abil-
ity of a meta or para substituent group to donate or
withdraw electrons in the equation
The reaction constant ρ is a measure of the sensi-
tivity of a reaction to the electronic substitution effect
and is unity for the dissociation of benzoic acid in
water. For acid-anion equilibrium, electron-donating
groups decrease the extent of dissociation and electron-
withdrawing groups increase the extent of dissociation
due to the effect of stability of the anion. Electron-
donating groups retard hydrolysis rates, whereas with-
drawing groups accelerate hydrolysis. A nucleophile
bearing an electron-donating group makes the carbon
atom of the carbonyl group of an ester more reactive.
The solvent of the reaction affects the reaction rate and
thus the reactivity of the substrates [22]. If the tran-
sition state has more electrons than the reactants then
ρ has a positive value. If the transition state has lesser
electrons than the reactants then ρ has a negative value.
That ortho-substituted aromatic compounds do not
conform to Hammett plots is well known and ac-
cepted. This is attributed to the possible steric hin-
drance that ortho substituents may exert resulting in
noncoplanarity of the substituent with the aromatic
ring leading to hampered delocalization, hence Ham-
mett plots are restricted to meta- and para-substituted
compounds [23,24]. In the studies carried out herein,
the slope of the Hammett plot, log k versus σx (Fig. 4),
is negative (–1.87), signifying the electrophilic substi-
tution nature of the reactions.
log kx = log kH + ρσx
where kx is a rate constant of the substituted substrate,
kH is the rate constant of the unsubstituted substrate, ρ
is a reaction constant, and σx is a substituent constant:
σx = log [Kx/KH] = (pKa)H − (pKa)
= (pKa)phenol − (pKa)substituted phenol
Moderate Negative Values of ꢀSꢀ= Are
Indicative of Bimolecular Reactions
where Kx is a dissociation constant of substituted phe-
nol (substituted carbolic acid) and KH is a dissociation
constant of unsubstituted phenol (carbolic acid)
The ability of a substituent to donate or withdraw
electrons was estimated by Hammett on the basis of
Such a fit of the observed kinetics for these nine substi-
tution reactions of phenol derivatives in the Hammett
plot was lacking for aqueous medium. The present
studies have attempted such a fit of the experimentally
observed values.
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700
BORKAR, BONDE, AND DANGAT
Figure 4 Hammett plot for the iodination reactions studied.
confirms the nonconformity of the ortho isomers while
CONCLUSIONS
is seen to hold good for the other isomers.
The electron-donating inductive effect of the CH3
group, the electron-donating mesomeric effects of the
substituents OH and Cl, the electron-withdrawing me-
someric effect of the NO2 group, all depend on their
nature and the position they occupy on the aromatic
ring along with steric compulsions. These factors op-
erating in unison determine the reactivity of the sub-
strates studied in these electrophilic substitutions us-
ing the iodine monochloride reagent. The quantitative
structure–reactivity assessment of the phenols studied
herein, by investigating the rapid iodination kinetics
ascertained by applying the Hammett equation, has
been plausible using the hydrodynamic voltammetry
technique.
The observed trends of the reaction rates for the iodi-
nation of nitrophenols, chlorophenols, and cresols are
complemented with those for the energies of activa-
tion, frequency factors, and entropy changes for these
reactions (Table I). The activated complex has lower
entropy of activation than the reactants; hence, it is un-
stable and decays into products. Increasing magnitudes
of the rate constants are seen to accompany decreasing
frequency factors, decreasing activation energies, and
increasing magnitudes of entropy of activation. These
trends are a quantitative measure of the reactivity order
of the substrates in these reactions and clearly mani-
fest the subtleties of the reactivity of these substrates
stemming from the contribution of the various factors
that affect the mechanistic route. The Hammett plot
The nine reactions under study are as follows:
Phenol
o-Cresol
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QUANTITATIVE STRUCTURE–REACTIVITY ASSESSMENT OF PHENOLS
701
m-Cresol
p-Cresol
o-Chlorophenol
m-Chlorophenol
p-Chlorophenol
m-Nitrophenol
p-Nitrophenol
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