Nucleophilic replacement of hydrogen in para-substituted nitrobenzenes by phenylacetonitrile carbanion

Article abstract of DOI:10.1023/A:1015315127634

The kinetic relations holding in nucleophilic replacement of hydrogen in para-substituted nitrobenzenes by phenylacetonitrile carbanion suggest a complex reaction mechanism involving two alternative pathways. The direction of the process is determined by the structure of intermediate σ-complex.

Full text of DOI:10.1023/A:1015315127634

Russian Journal of Organic Chemistry, Vol. 38, No. 1, 2002, pp. 100 103. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 1, 2002,
pp. 108 111.
Original Russian Text Copyright
2002 by Orlov, Sokovikov, Kotov.
Nucleophilic Replacement of Hydrogen in para-Substituted
Nitrobenzenes by Phenylacetonitrile Carbanion
V. Yu. Orlov, Ya. V. Sokovikov, and A. D. Kotov
Demidov Yaroslavl State University, ul. Sovetskaya 14, Yaroslavl, 150000 Russia
e-mail: orl@bio.uniyar.ac.ru
Received August 2, 2000
Abstract The kinetic relations holding in nucleophilic replacement of hydrogen in para-substituted nitro-
benzenes by phenylacetonitrile carbanion suggest a complex reaction mechanism involving two alternative
pathways. The direction of the process is determined by the structure of intermediate -complex.
Nucleophilic replacement of hydrogen in para-sub-
stituted nitrobenzenes Ia Ii by carbanion generated
in situ (ethanolic alkali) from phenylacetonitrile (II)
leads to formation of the corresponding 2,1-benziso-
xazoles IIIa IIIi (Scheme 1).
yields of the products were almost quantitative, and
neither accumulation of intermediate products nor
formation of by-products was observed (Fig. 1). The
kinetic measurements were performed under pseudo-
first-order conditions using the isolation technique [3],
i.e., all reactants, except for the nitroaromatic sub-
strate, were taken in a large excess. The order of the
reaction and its rate constant were determined from
the kinetic curves by the van’t Hoff method and by
integration [4]. The results obtained by the two
methods almost coincided. It should be noted that
the reaction rate does not depend on the order of
mixing of the reactants and that the kinetic parameters
determined from variation of the concentrations of
4-nitrochlorobenzene (Ia) and benzisoxazole IIIa were
similar. These findings indicate a high reactivity of
intermediates. The reaction order with respect to the
substrate and reagent is equal to unity.
Scheme 1.
I, III, R = Cl (a), Br (b), I (c), 1-methyl-1,3-dioxolan-2-yl
(d), 1,3-dioxolan-2-yl (e), Ph (f), OPh (g), 2,4-Cl2C6H3O
(h), 4-PhC6H4O (i).
The synthetic aspect of nucleophilic substitution
of hydrogen has been extensively studied [1, 2];
however, very limited published data are available
on quantitative, in particular kinetic relations holding
in this process. The lack of such information makes
it difficult to formulate a general concept of the
reaction mechanism. Therefore, the present com-
munication reports the results of our study on the
kinetics of the reaction outlined in Scheme 1.
The progress of the reaction was monitored follow-
ing the concentrations of initial nitro compounds I
and final 2,1-benzisoxazoles III. The concentrations
of I and III were determined by polarography. The
Fig. 1. Kinetic curves for (1) consumption of p-nitro-
chlorobenzene (Ia) and (2) appearance of 5-chloro-3-
phenyl-2,1-benzisoxazole (IIIa) in the reaction of Ia with
phenylacetonitrile carbanion.
1070-4280/02/3801-0100$27.00 2002 MAIK Nauka/Interperiodica

NUCLEOPHILIC REPLACEMENT OF HYDROGEN
101
Apparent activation parameters of the reaction of substituted nitrobenzenes Ia, Ie, and Ih with carbanion generated from
phenylacetonitrile (II)
Comp.
no.
Temperature
range, K
1
Ea, kJ/mol
H, kJ/mol
S, J mol 1 K
G, kJ/mol
lnA
Ia
303 314
314 328
303 328
303 314
314 328
29.2 1.5
91.4 3.9
42.6 1.8
5.8 1.3
26.6 1.3
88.7 4.0
40.0 1.3
3.2 1.1
252.0 13
57.7 2.5
192.7 12
310.8 15
230.9 3.5
104.3 1.3
107.2 4.0
100.8 1.3
99.1 1.1
2.41 0.02
25.9 0.1
6.3 0.05
1.8 0.1
Ie
Ih
31.2 3.7
28.6 3.8
102.7 3.8
7.9 0.1
Preliminary study of the temperature dependence of
The results are shown in Fig. 4. The plots obtained
the reaction rate in the range from 303 to 328 K gave in both temperature ranges have similar shapes. We
unexpected results. The lnkap 1/T dependences for
nitrochlorobenzene Ia and ether Ih have an inflection
point (Fig. 2). Such shape of the Arrhenius plot
suggests that the process takes two pathways. It
should be noted that within both temperature intervals
(before and after inflection point) the same product
is formed, 5-substituted 3-phenyl-2,1-benzisoxazole.
Therefore, change of the reaction pathway with rise
in temperature does not result in formation of another
final product but involves variation of intermediate
stages. The lnkap 1/T plot for nitro compound Ie
has no inflection. Presumably, this is explained by
suppression of one of the alternative pathway or by
location of the inflection point beyond the examined
temperature range. The thermodynamic parameters of
the reactions with nitro compounds Ia, Ie, and Ih are
given in table.
tried to interpret them with the aid of acceptor number
Fig. 2. Plots of lnkap versus 1/T for the reactions of
(1) 4-chloronitrobenzene (Ia), (2) 2,4-dichloro-4 -nitro-
diphenyl ether (Ih), and (3) 4-(1,3-dioxolan-2-yl)nitroben-
Taking into account the existence of two alternative
pathways for formation of 2,1-benzisoxazoles, the
subsequent kinetic measurements were performed at
303 K (the first branch of the Arrhenius plot) and
320 K (the second branch of the Arrhenius plot).
zene (Ie) with phenylacetonitrile (II); cI = 0.03 M, cII
0.435 M, cNaOH = 1.25 M.
=
Figure 3 shows the effect of alkali concentration
on the rate of the reaction of chloronitrobenzene Ia
with phenylacetonitrile. The plots of kap versus alkali
concentration at 303 and 320 K are similar. The corre-
sponding curves are described by the equations
4
3
kap = 3 10 cNaOH
0.0001 (303 K)
and
6
3
kap = 5 10 cNaOH + 0.0007 (320 K).
The nonlinear character of these dependences
suggests a complex mechanism of participation of
alkali in the process.
We also examined the kinetic parameters of the
reactions carried out in aliphatic alcohols as solvents.
Fig. 3. Plots of kap versus alkali concentration cNaOH for
the reaction of 4-chloronitrobenzene (Ia) with phenylaceto-
nitrile (II) at (1) 320 K (y = 0.000005x3 + 0.0007; R2 =
0.9839) and (2) 303 K (y = 0.0003x3
0.9991); cIa = 0.020 M, cII = 0.435 M.
0.0001; R2
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

102
ORLOV et al.
position of the reaction center is determined by the
frontier orbital structure. Rusakov et al. [7, 8] demon-
strated the applicability of the Klopman combined
reactivity index ( Ers) [9] to some nucleophilic sub-
stitution reactions:
2
qr qs r
ace uno 2(Crm Csn )
Ers
=
+
+
.
solv
m
n
En*
Em*
Here, r and s are the indices of the reaction centers,
is the dielectric constant of the solvent, r is a term
characterizing Coulomb repulsion between the r and
s atoms, m is the occupied orbital of the donor,
n is the vacant orbital of the acceptor, c is the elec-
tron density on the frontier orbitals of the reaction
Fig. 4. Plots of lnkap versus acceptor number of the
solvent for the reaction of 4-chloronitrobenzene (Ia) with
phenylacetonitrile (II) at (1) 320 K (y = 0.4457x + 9.1235,
R2 = 0.9703) and (2) 303 K (y = 0.6114x + 13.485, R2 =
0.8937); cIa = 0.020 M, cII = 0.435 M, cNaOH = 0.750 M.
center, and
is the resonance integral.
Taking into account that the substrate reaction
center is characterized by the LUMO structure and
that the contribution of the reagent is constant, the
parameter Ers is expressed by the equation
(AN), i.e., the parameter characterizing electrophilic
properties of a solvent [5]. Figure 4 shows that the
reaction slows down as AN increases at both 303 and
320 K. This is explained by stronger solvation of
phenylacetonitrile carbanion than of intermediate
-complex; as a result, the activation barrier increases.
Our data indicate that in the two temperature ranges
the rate-determining stage is formation of intermediate
-complex.
In order to interpret the dependence of the reaction
rate on the substrate structure we invoked an approach
based on simulation of orbital interactions, namely
between the highest occupied molecular orbital
(HOMO) of the substrate and the lowest unoccupied
molecular orbital (LUMO) of the reagent. We pre-
viously found [6] that in the formation of 2,1-benz-
isoxazoles from para-substituted nitroarenes the
Ers = C2pz/ E,
where C2pz is the orbital coefficient of the carbon atom
neighboring to the nitro group and E is the energy
difference between the LUMO of the substrate and
HOMO of the reagent.
The Ers values of the substrates were derived
from the results of AM1 quantum-chemical calcula-
tions. Figure 5 shows the dependences of lnkap versus
Ers. The linear character of the lnkap
Ers plots
(r2 = 0.95 and r1 = 0.92) leads us to presume that
the rate-determining stage is formation of new C C
bond. It is notable that analogous relations were
obtained for both temperature intervals.
As stated above, the lnkap 1/T dependences for
different 4-substituted nitroaromatic substrates are
similar. However, the activation parameters for the
reaction with ether Ih, calculated from the lnkap 1/T
dependence, turned out to be anomalously low. The
low activation energy implies a weak temperature
effect on the reaction rate. In some cases this may
be due to formation of contact ion pairs, specifically
between sodium cation and phenylacetonitrile anion.
However, the formation of such ion pairs in the reac-
tion under study is hardly probable, for aliphatic
alcohols solvate well both cations and anions. The
dependence of kap on the solvent acceptor numbers
also indicates that contact ion pairs are not formed.
Furthermore, replacement of sodium hydroxide by
potassium hydroxide and addition of a crown ether
did not affect the reaction rate. Presumably, the low
Fig. 5. Plots of lnkap versus Ers for the reaction of sub-
stituted nitrobenzenes I with phenylacetonitrile (II) at
(1) 320 K (y = 124.07x 19.449, R2 = 0.048) and (2) 303 K
(y = 103.55x 18.607, R2 = 0.9228); cI = 0.0104 M, cII
0.435 M, cNaOH = 1.250 M.
=
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NUCLEOPHILIC REPLACEMENT OF HYDROGEN
103
energy of activation is explained by the fact that the
reaction occurs under isoparametric conditions [10].
reaction mixture were withdrawn when necessary and
were immediately analyzed by polarography. The
polarographic measurements were performed with the
aid of an LP-7 instrument (CzSSR); a 0.1 M solution
of sulfuric acid containing 50% of DMF was used as
supporting electrolyte. Quantum-chemical calculations
were performed using MOPAC 7.0 software package.
On the basis of the temperature dependence of the
apparent rate constant we concluded that 2,1-benziso-
xazoles are formed via two concurrent pathways with
different activation barriers. The kinetic studies per-
formed at 303 and 320 K showed that both pathways
involve the same rate-determining stage and are
characterized by analogous dependences of the ap-
parent rate constant on the concentration of alkali,
solvent nature, and substituent in the substrate. We
presume that the two pathways involve formation of
isomeric -complexes. Some examples of formation
of such isomers have been reported [11]. Addition of
phenylacetonitrile carbanion to chloronitrobenzene Ia
gives -complex IV possessing two asymmetric
carbon atoms. Therefore, formation of four isomeric
-complexes could be expected. Their structure was
simulated by quantum-chemical calculations.
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with protection from moisture, maintaining the tem-
perature with an accuracy of 0.5 C. Samples of the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002