Kinetics of alkaline hydrolysis of p-substituted benzylidenemalononitriles in 50% aqueous acetonitrile: Substituent effects and quantification of the electrophilic reactivity

Article abstract of DOI:10.1002/poc.3286

The rate constants of the reaction of p-X-substituted benzylidenemalononitriles 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h with hydroxide ion were measured in 50% water-50% acetonitrile at 20 C. The experimental kinetic data reveal that the points pertaining to electron donating substituted compounds (X = Me, OMe and NMe₂) exhibit negative deviations from the Hammett plot. However, the Yukawa-Tsuno plot for the same rate constants resulted in a good straight line with an excellent correlation coefficient (r² = 0.9916) and an r value of 1.15. Possible ground-state stabilization through resonance interactions has been suggested to explain the origin of the nonlinear Hammett plot. On the basis of the relationship between E and σ_p⁺, the electrophilicity parameter E of some benzylidenemalononitriles 1c and 1e, 1f, 1g, 1h has been evaluated. More importantly, the three compounds 1f (E = -7.90), 1g (E = -7.80) and 1h (E = -7.55) exhibit high electrophilicities that compare well with that of 4,6-dinitrobenzoselenadiazole (E = -7.40), a compound which has a general behaviour representative for the superelectrophilic dimension. We have shown that the second-order rate constants calculated from Mayr's approach for the reaction of 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h with hydroxide ion do not agree with the available experimental data. On the other hand, a good linear correlation between log k_exp and log k_calc has been observed and discussed.

Full text of DOI:10.1002/poc.3286

Research Article
Received: 29 October 2013,
Revised: 2 January 2014,
Accepted: 6 January 2014,
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/poc.3286
Kinetics of alkaline hydrolysis of p-substituted
benzylidenemalononitriles in 50% aqueous
acetonitrile: substituent effects and
quantification of the electrophilic reactivity
Nejeh Dhahria, Boubaker Taoufika* and Régis Goumontb**
The rate constants of the reaction of p-X-substituted benzylidenemalononitriles 1a–h with hydroxide ion were measured in 50%
water–50% acetonitrile at 20°C. The experimental kinetic data reveal that the points pertaining to electron donating substituted
compounds (X= Me, OMe and NMe2) exhibit negative deviations from the Hammett plot. However, the Yukawa–Tsuno plot for
the same rate constants resulted in a good straight line with an excellent correlation coefficient (r2 = 0.9916) and an r value of
1.15. Possible ground-state stabilization through resonance interactions has been suggested to explain the origin of the
nonlinear Hammett plot. On the basis of the relationship between E and σp+, the electrophilicity parameter E of some
benzylidenemalononitriles 1c and 1e–h has been evaluated. More importantly, the three compounds 1f (E = ꢀ7.90), 1g
(E = ꢀ7.80) and 1h (E = ꢀ7.55) exhibit high electrophilicities that compare well with that of 4,6-dinitrobenzoselenadiazole
(E = ꢀ7.40), a compound which has a general behaviour representative for the superelectrophilic dimension. We have shown that
the second-order rate constants calculated from Mayr’s approach for the reaction of 1a–h with hydroxide ion do not agree with
the available experimental data. On the other hand, a good linear correlation between log kexp and log kcalc has been observed
and discussed. Copyright © 2014 John Wiley & Sons, Ltd.
Keywords: alkaline hydrolysis; electrophilicity; kinetics; linear free energy relationship; substituent effects
substituent and the C = C bond. The electronic effect of the substit-
uents on the reactivity of BMN has also been investigated. On the
INTRODUCTION
other hand, these studies have allowed the evaluation of electrophi-
licity parameters E of this series of electrophiles. With E parameters
in the range of ꢀ7.55 to ꢀ9.98, the electrophilicities of these
p-X-substituted BMN are comparable to those of some other
electron-deficient neutral aromatic substrates.
Substituted benzylidenemalononitriles (BMN) constitute an in-
teresting class of compounds because of their importance in
biological processes as well as in synthetic organic chemical
applications.[1–6] Interestingly, these compounds have been used
as rodent control agents and as cytotoxic agents against
tumours.[7] It is noteworthy to underline that the physiological
effects of this series of compounds are dependent upon the
position and the nature of the substituent borne by the aromatic
ring. In fact, injections of p-nitro-BMN in mice with cancerous
tumours are leading to a reduction in tumour size.[8]
(1)
The reactions of p-X-substituted BMN (X = NMe2, OMe and H)
with stabilized carbanions have been recently reported by Lemek[5]
and have revealed that the electrophilicity parameter E of the least
reactive compound (X = NMe2: E = ꢀ13.29) is essentially the same
than that of 1,3,5-trinitrobenzene (E = ꢀ13.19), the conventional
reference aromatic electrophile in nucleophilic addition chemistry.
These results suggest that the chemistry of substituted BMN is
highly dependent on their electrophilic character.
In this paper, we describe further studies improving the under-
standing of the reactivity of BMN with nucleophiles. We report a
detailed kinetic investigation of the reactions of p-X-substituted
BMN 1a–h (X = NMe2, OMe, CH3, H, Cl, CF3, CN and NO2) with
hydroxide ion OHꢀ in 50% water–50% acetonitrile at 20 °C (Eqn (1)).
As will be seen, the results have shown that the nonlinear Hammett
plot could be interpreted in terms of ground-state stabilization
through resonance interactions between the electron donating
* Correspondence to: Boubaker Taoufik, Laboratoire C.H.P.N.R, Faculté des
Sciences de Monastir, Université de Monastir, Avenue de l’Environnement, 5019
Monastir, Tunisie. E-mail: boubaker_taoufik@yahoo.fr
**Correspondence to: Régis Goumont, Institut Lavoisier de Versailles, UMR 8180,
Université de Versailles, 45, Avenue des Etats-Unis, 78035 Versailles Cedex, France
E-mail: goumont@chimie.uvsq.fr
a N. Dhahri, B. Taoufik
Laboratoire C.H.P.N.R, Faculté des Sciences de Monastir, Université de Monastir,
Avenue de l’Environnement, 5019 Monastir, Tunisie
b R. Goumont
Institut Lavoisier de Versailles, UMR 8180, Université de Versailles, 45, Avenue
des Etats-Unis, 78035 Versailles Cedex, France
J. Phys. Org. Chem. 2014
Copyright © 2014 John Wiley & Sons, Ltd.

N. DHAHRI, B. TAOUFIK AND R. GOUMONT
lines (correlation coefficients of the linear regressions were usually
higher than 0.99…). The kobsd values obtained are collected in
Table S1 in Supporting Information.
RESULTS AND DISCUSSION
Kinetic studies
The alkaline hydrolysis of a series of olefins 1a–h in 50% water–
50% acetonitrile at 20°C was followed spectrophotometrically by
measuring the decrease in the absorption at the λmax of the olefin
1, 440 nm (X= NMe2), 350 nm (X= OMe), 326 nm (X= Me), 308nm
(X= H), 317 nm (X= Cl), 292 nm (X= CF3), 301nm (X= CN) and
308 nm (X = NO2). All experiments were carried out under
pseudo-first order conditions with a 5 × 10ꢀ5 mol dmꢀ3 of the ole-
fin 1 and a large excess (10ꢀ3 – 10ꢀ1 mol dmꢀ3) of the hydroxide
ion. It has to be noted that only one relaxation time correspond-
ing to the quantitative formation of the products 2a–h was
observed (Fig. 1). Pseudo first-order rate constants, kobsd, were
obtained using Eqn (2), where A∞ refers to the absorbance of
the product 2a–h at the completion of the reaction; Ao refers to
the absorbance at zero time, and At refers to the absorbance at
time. A plot of Ln (A∞ ꢀ At) versus time gave very good straight
LnðA∞ ꢀ AtÞ ¼ ꢀkobsdt þ LnðA∞ ꢀ AoÞ
(2)
All the reactions studied in the present work followed a simple
kinetic law given by Eqn (3), where k is the second-order rate con-
stant for the hydroxide ion addition to the olefins 1a–h. Figure 1
shows the absorbance variation at λmax =326nm versus time for
the reaction of 4-methylbenzylidenemalononitrile 1c (5 × 10ꢀ5 mol
dmꢀ3) with various NaOH concentrations at 20 °C. The second-order
rate constants, k, have been determined from the slope of the linear
plots of kobsd versus [OHꢀ] and summarized in Table 1.
kobsd ¼ k½OHꢀꢁ
(3)
Substituent effects
The Hammett plot[9] for the reactions of olefins 1a–h with
hydroxide ion obtained in 50% water–50% acetonitrile shows an
unambiguous evidence of a nonlinear behaviour (Fig. 2). In fact,
two straight lines exhibiting two different slopes are observed: a
lower slope value (ρ =1.54; σp > 0) for electron-withdrawing substitu-
ents and a greater slope value (ρ =2.83; σp < 0) for electron-donating
substituents. This change in the slope of the plots with two
intersecting straight lines could clearly show a sudden change in
the rate-determining step or a change in the mechanism implying
the reaction of BMN with hydroxide ion.
Kinetic data have also been analysed using a Yukawa–Tsuno
Eqn (4) in which r and (σ+ ꢀ σ) represent the relative extend
value of the resonance contribution and the resonance substitu-
ent constant measuring the capacity for π-delocalization of a
given π-electron donor substituent, respectively.[10]
0.80
a)
0.70
b)
0.60
0.50
0.40
0.30
0.20
0.10
0.00
0
50
100
150
200
log kX1=kH1 ¼ ρðσ þ rðσþ ꢀ σÞÞ
(4)
t / s
Figure 1. (a) Plot of the absorbance at λmax = 326 nm versus time for the
reaction of 4-methylbenzylidenemalononitrile 1c (5 × 10ꢀ5 mol dmꢀ3
)
As can be seen, the Yukawa–Tsuno plot (Fig. 3) for the reac-
tions of olefins 1a–h with hydroxide ion exhibits straight line
(R2 = 0.9916) with ρ = 1.34 and r = 1.11. Such a linear plot clearly
indicates that the resonance contribution is responsible for the
negative deviation shown by olefins 1a–c (e.g. for reactions with
with NaOH (10ꢀ3 – 8 × 10ꢀ3 mol dmꢀ3) at 20 °C in 50% water–50%
acetonitrile. (b) Influence of the concentration of the hydroxide ion on
the observed pseudo first-order rate constants kobsd for addition to 1c
in 50% water–50% acetonitrile at 20 °C
Table 1. Experimental second-order rate constants (kexp) for addition reactions of hydroxide ion with benzylidenemalononitriles 1a–h
in 50% water–50% acetonitrile at 20°C and comparison with rate constants (kcalc) calculated from Mayr equation (log k (20 °C) = s
(E + N))
σ+
kexp (molꢀ1 dm3 sꢀ1
)
kcalc (molꢀ1 dm3 sꢀ1
)
kexp / kcalc
a
b
Substituent X
σ
NMe2
OMe
Me
H
Cl
CN
ꢀ0.83
ꢀ0.27
ꢀ0.17
0
0.23
0.54
0.66
0.78
ꢀ1.70
ꢀ0.78
ꢀ0.31
0
0.11
0.61
0.66
0.79
2.04 × 10ꢀ1
7.92
13.58
47.9
120
307
1.20 × 10ꢀ2
4.10 × 10ꢀ1
1.34
3.00
5.26
26.2
30.4
46.4
17
19
10
16
23
12
16
19
CF3
NO2
487
881
aDetermined in this work from the slope of plots of kobsd versus [OHꢀ]. b Calculated from the Mayr equation log k = s(E + N).[39] The
σ and σ+ values were taken from ref. [9]
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A DETAILED STUDY OF THE REACTIVITY OF BENZYLIDENEMALONONITRILES IN 50% AQUEOUS ACETONITRILE
On the other hand, the correlation line in Fig. S1, which has
been obtained on plotting rate constants (log k) determined in
50% water–50% acetonitrile versus log k determined in water
by Bernasconi and co-workers[11], indicates that the structure of
the transition state is not significantly modified by the change
of the X-substituent and by the change of reactional medium
and could be an additional evidence in favour of a similar reac-
tion mechanism. Even if similar experiments have been carried
out by Bernasconi in water,[11] our results bring some new
information in the study of the influence of the substituent of
the aromatic ring in the kinetic of the reaction of BMN with
OHꢀ. Five new compounds possessing electron-withdrawing
substituent such as CF3, CN and NO2 have been studied, and
their reactivity has been compared with those of three other
compounds studied by Mayr.[5] During our study, no problem
of solubility has been observed in the case of NaOH in these
media. Finally, it has to be noted that the E value is not depen-
dent of the solvent and so comparison of E values, measured in
various media, can be made.
Figure 2. Hammett plot for reactions of benzylidenemalononitriles 1a–h
with hydroxide ion in 50% water–50% acetonitrile at 20 °C. σp values taken
from ref [9]
Thus, it can reasonably be concluded that the origin of the
nonlinear Hammett plot (Fig. 2) associated with the reactions of ole-
fins 1a–h with hydroxide ion results from ground-state stabilization
through resonance interactions as illustrated by the resonance
structures I and II, rather than from a change in the rate-determining
step or a change in mechanism for the reaction.
Quantification of the electrophilic reactivity
Using as reference the three electrophilicity parameters E values
of olefins 1a (E = ꢀ13.29), 1b (E = ꢀ10.81) and 1d (E = ꢀ9.42)
reported by Mayr and co-workers,[5] plot of these E values against
their Brown constants σp+ has been drawn (Fig. S2 in Supporting
Information). As can be seen, the relationship between E and
σp+ is linear and results in the following equation
ðr2 ¼ 0:9941Þ
þ
Figure 3. Yukawa–Tsuno plot for reactions of benzylidenemalononitriles
1a–h with hydroxide ion in 50% water–50% acetonitrile at 20 °C. σp and
σp+ values taken from ref [9]
(5)
E ¼ ꢀ9:29 þ 2:26 σp
It is interesting to note that these types of relationships, E versus
σ+, have also been reported by many authors.[15–17] For example,
linear correlation between the Hammett’s σ+ constants and the
electrophilicity parameters E of the symmetrically substituted
benzhydrylium cations has been obtained (σ+ = 0.134E ꢀ 0.767,
r = 0.9986) and used to determine the σ+ parameters of a series
of new donor substituents.[17]
Using Eqn (5), the E parameters of 1c and 1e–h have been
determined. The E values are summarized and compared in Fig. 4
with those previously obtained for neutral electron-deficient
heteroaromatic and aromatics structures 3–8[18,19] together with
substrates 9[20] and 10[21] studied by Mayr and co-workers.
As can be seen in Fig. 4, the E parameters of the p-substituted
benzilidenemalononitrile 1a–h cover a domain of electrophilic
reactivity of 6 orders of magnitude from the weakest electrophile
1a determined by Mayr and co-workers,[5] to the strongest ones,
olefins 1f–h studied in the present work. Also, Fig. 4 reveals
that the most reactive benzilidenemalononitrile used in this
electron-donating substituents). It is important to mention that
the kinetic data of the same type of reactions, performed` in
water, have been reported by Bernasconi and co-workers. In this
latter case, the linear log k versus σ+ plot is characterized by a ρ
value of 1.39 0.17.[11] The fact that the two ρ values are quite
similar in both media (water and an acetonitrile–water mixture)
suggests that the changes in charge distribution due to charge
delocalization are similar in both solvents.
The deviations from Hammett plots based on standard σ-values
have been observed by many authors.[12–14] Um and co-workers,
for example, have interpreted the negative deviations obtained
for reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates
with piperidine and piperazinium in 80 mol % H2O/20 mol %
DMSO at 25 °C in terms of stabilization of the ground-state
through resonance between the electron donating substituent
and the sulfonyl or carbonyl group.[12a]
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N. DHAHRI, B. TAOUFIK AND R. GOUMONT
Figure 4. Comparison of the electrophilicity parameters E of p-X-substituted benzylidene malononitriles 1c and 1e–h with those of electron-deficient
neutral electrophilic substrates
study, i.e. 1h (E= ꢀ7.55) displays an electrophilicity that compares
well with those of 4-nitro-6-cyanobenzofuroxan 4 (E= ꢀ7.01),[18] of
4,6-dinitrobenzoselenadiazole 5 (E= ꢀ7.40)[19] and of (ethene-1,1-
diyldisulfonyl)dibenzene 9 (E= ꢀ7.50),[20] indicating a superelect-
rophilic ranking of 1h in the Mayr’s scale.[5,22] Nevertheless, this
E value remains lower than that of 4,6-dinitrotetrazolopyridine 3
(E= ꢀ4.67),[18a] one of the most electrophilic neutral compounds
known to date. Recently, Mayr has shown that DDQ (2,3-dichloro-
5,6-dicyano-p-benzoquinone), with an E value of ꢀ3.66 is, at the
moment, the most electrophilic neutral compound.[18b]
that BMN 1f–h belong to the superelectrophiles family. Previous
studies have shown that an E parameter of ꢀ8.50 is the boundary
demarcating super- and normal electrophilicity.[5,23a]
log kexp versus log kcalc relationships
According to the electrophilicity parameters E of p-X-substituted
BMN 1a–h (Fig. 4) and the values of nucleophile specific parameters
N= 10.19 and s = 0.62 previously measured in 50–50 (v/v) water–
acetonitrile,[30] second-order rate constants of reactions of these
olefins 1a–h with hydroxide ion at 20 °C are calculated using the
Mayr Eqn (6).[31–39] These results are summarized in Table 1.
Interestingly, the E parameters of 1c and 1e–h have also
shown that these compounds are considerably higher electron-
deficient structures than 2,4-dinitrothiophene 6[18] and 1,3,5-
trinitrobenzene 7,[18] the conventional aromatic electrophile in
nucleophilic addition or substitution processes.[23–29] On the other
hand, the olefin 1e (E= ꢀ9.03) has an E value comparable to those
of dibenzyl azodicarboxylate 10 (E = ꢀ8.89)[21] and of benzotriazole
8 (E= ꢀ9.16).[19]
log kð20°CÞ ¼ sðE þ NÞ
(6)
A rapid comparison of the kinetic data reported in Table 1
shows that the experimental rate constants (kexp) are 10–23
orders of magnitude higher than the calculated (kcalc) by Eqn (6).
Interestingly, kexp/kcalc ratios of this order have also been reported
for the reactions of 4-X-substituted BMN 1a (kexp/kcalc ≈ 7), 1b
With E parameters higher than ꢀ8, the ranking of the three most
reactive BMN 1f–h on the kinetic scale is informative, revealing
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A DETAILED STUDY OF THE REACTIVITY OF BENZYLIDENEMALONONITRILES IN 50% AQUEOUS ACETONITRILE
(kexp/kcalc ≈ 14) and 1d (kexp/kcalc ≈ 8) with piperidine in 50%
aqueous DMSO.[40] However, in some other cases, and especially
in the case of the reactions of unsubstituted BMN 1d with CH
(CN)ꢀ2 in water at 20 °C, the experimental rate constants only differ
from those of the calculated ones by 0.8.[41] It is interesting to note
that the differences between calculated rate constants from the
three parameters Eqn (6) and the experimental ones have re-
ceived considerable attention though these deviations are still
not completely understood.[17,42–45,34]
A most relevant feature, however, was the finding that the
experimental log kexp values of reaction of 1a–h with OHꢀ are lin-
early related to the calculated log kcalc, defining a good correlation,
Eqn (7), with a slope close to unity.
log kexp ¼ 0:99 logkcalc þ 1:20 ðr2 ¼ 0:9954Þ
(7)
Analogous correlations have been established in the case of the
Figure 5. Correlations between log kexp and log kcalc. (●) Reactions of
reaction of indole 11d with p-substituted benzenediazonium cation
12a–f in acetonitrile solution at 25 °C[46] (Eqn (8), Fig. 5) and of the
reaction of a series of substituted benzofuroxans 13a–d with OHꢀ
in aqueous solution at 20 °C[47,22] (Eqn (9), Fig. 5). The following Eqns
(10) and (11), respectively, describe this linear dependence.
p-X-substituted benzylidene malononitriles 1a–h with hydroxide ion at
20 °C in 50–50 (v/v) water–acetonitrile. ( ) Reactions of indole 11 with
p-substituted benzenediazonium cation 12a–f in acetonitrile solution at
25 °C (○). Reaction of a series of substituted benzofuroxans 13a–d with
OHꢀ in aqueous solution at 20 °C
(8)
CONCLUSION
In this work, the Hammett plot for reactions of p-X-substituted
BMN 1a–h with hydroxide ion in 50% water–50% acetonitrile
at 20 °C has been reported. The negative deviations from the
Hammett plot have been explained in terms of ground-state sta-
bilization through conjugative interaction between substituents
and the C = C double bonds. The E versus σ+ correlation has been
used for an evaluation of the electrophilicity of BMN 1c and 1e–h.
The electrophilic character of the three olefins 1f–h has been
shown to be closer to that of the superelectrophilic reference, i.
e. 4,6-dinitrotetrazolopyridine 3 (E = ꢀ4.67), than to that of 1,3,5-
trinitrobenzene 7 (E = ꢀ13.19), the conventional aromatic electro-
phile in σ-complex chemistry. On the other hand, we have
reported, for the first time, that experimental and calculated
second-order rate constants are closely correlated for a reaction
involving a series of compounds. It could be the starting point
of further studies to better understand the factors governing the
differences between experimental and calculated second-order
rate constants which could be other than those reported in litera-
ture such as steric or solvent effects.
(9)
log kexp ¼ 1:04 logkcalc ꢀ 0:50 ðr2 ¼ 0:9822Þ
log kexp ¼ 1:04 logkcalc þ 1:04 ðr2 ¼ 0:9870Þ
(10)
(11)
As can be seen, the slopes of these relationships are still very
close to unity revealing that the three correlations (7), (10) and
(11) are similar in form but differing from the existence of an ad-
ditional constant, corresponding to the intercept of the straight
lines obtained on plotting log kexp versus log kcalc with the
abscissa axis. These results allow a rewriting of the Eqn (6) in
which the second-order rate constant could be predicted by
Eqn (12), C being the intercept value previously seen.
EXPERIMENTAL SECTION
Materials
The p-X-substituted BMNs 1 were prepared as previously reported.[48]
The coupling reactions of 1a–h with hydroxide ion OHꢀ studied in the
present work were kinetically followed by the stopped-flow technique.
Measurements were performed on a stopped-flow spectrophotometer
(Biologic), being equipped with a thermostated cell compartment
(20 °C 0.1). A conventional spectrophotometer (Shimadzu, model 1650
PC) coupling with a thermo-electrically temperature controlled cell
holder (model TCC-240 A) was also used to follow the slowest processes.
All kinetic runs were carried out in triplicate under pseudo first-order
conditions. In a given experiment, the rates were found to be repro-
ducible to 2–3%.
log kð20 °CÞ ¼ sðE þ NÞ þ C
(12)
This new equation could imply that the three parameters E, N
and s are not enough to determine the rates constants of the
nucleophile–electrophile combinations needing an additional
term. Further studies are envisioned to better understand the
meaning of the Eqn (12), the factors being responsible for such
differences between experimental and calculated rate constants
and finally the significance of the intercept.
J. Phys. Org. Chem. 2014
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N. DHAHRI, B. TAOUFIK AND R. GOUMONT
[25] I. Jamaoui, T. Boubaker, R. Goumont, Int. J. Chem. Kinet. 2012, 45,
152–160.
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