Reactivity of phthalocyanine precursors

Article abstract of DOI:10.1007/s11172-015-1096-y

A higher reactivity of 4-nitrophthalonitrile as compared to phthalonitrile and 4-amino-phthalonitrile in the reaction with sodium methoxide in methanol was demonstrated by theoretical (semiempirical, ab initio calculations) and experimental methods. The regioisomeric composition of substituted methoxyiminoisoindolenines was studied by analysis of products of their reaction with p-toluidine. The higher reactivity of 3-imino-1-methoxyisoindolenine as compared to 1,3-diiminoisoindoline in the reactions with nucleophilic agents (ammonia, p-toluidine) was shown by semiempirical calculations and kinetic methods.

Full text of DOI:10.1007/s11172-015-1096-y

Russian Chemical Bulletin, International Edition, Vol. 64, No. 8, pp. 1933—1941, August, 2015
1933
Reactivity of phthalocyanine precursors*
A. V. Lyubimtsev,a,b N. V. Zheglova,a E. N. Smirnova,a and S. A. Syrbua,b
aIvanovo State University of Chemistry and Technology,
7 Sheremetevskii prosp., 153000 Ivanovo, Russian Federation.
Fax: +7 (493 2) 41 7995. Eꢀmail: alexlyubimtsev@mail.ru
bResearch Institute of Macroheterocyclic Compounds,
7 Sheremetevskii prosp., 153000 Ivanovo, Russian Federation.
Fax: +7 (493 2) 41 7995. Eꢀmail: alexlyubimtsev@mail.ru
A higher reactivity of 4ꢀnitrophthalonitrile as compared to phthalonitrile and 4ꢀaminoꢀ
phthalonitrile in the reaction with sodium methoxide in methanol was demonstrated by theoꢀ
retical (semiempirical, ab initio calculations) and experimental methods. The regioisomeric
composition of substituted methoxyiminoisoindolenines was studied by analysis of products of
their reaction with pꢀtoluidine. The higher reactivity of 3ꢀiminoꢀ1ꢀmethoxyisoindolenine
as compared to 1,3ꢀdiiminoisoindoline in the reactions with nucleophilic agents (ammonia,
pꢀtoluidine) was shown by semiempirical calculations and kinetic methods.
Key words: phthalonitrile, 4ꢀnitrophthalonitrile, 4ꢀaminophthalonitrile, reactivity, 3ꢀiminoꢀ
1ꢀmethoxyisoindolenine, 1,3ꢀdiiminoisoindoline, semiempirical and ab initio quantum chemiꢀ
cal calculations, density functional theory, functional B3LYP.
Together with traditional application of phthaloꢀ
cyanines (PCs) and their metal complexes as pigments and
dyes,1—3 these compounds are used in other highꢀtech
fields: as semiconductor materials, gas sensors, in molecꢀ
ular electronics, in nonlinear optics, etc.4—14 A recent inꢀ
crease in the interest to these compounds is caused by
a possibility of their use as sensitizers for photodynamic
therapy (PDT) of cancer and in other fields of mediꢀ
cine.15—23
A multitude of approaches to the preparation of PCs
and their metal complexes24,25 gives no chance to unamꢀ
biguously determine the mechanism of their formation.
A detailed analysis of the mechanistic aspects of
phthalocyanine macrocycle formation will make it possiꢀ
ble to purposefully and more efficiently conduct modifiꢀ
cation of these compounds at both the macrocycle peꢀ
riphery and the coordination center. An efficient inꢀ
strument helping to more deeply understand the mechaꢀ
nisms of formation of PCs, as well as to reasonably predict
new phthalocyanine systems with practically useful propꢀ
erties is a combination of theoretical and experimental
approaches based on the systematic application of upꢀtoꢀ
date quantum chemical methods and quantitative evaluaꢀ
tion of reactivity of starting compounds and intermediate
products of their synthesis.
Phthalonitrile and its derivatives are the most widely
used precursors of PCs for their synthesis.25 As a rule, the
use of these precursors provides higher yields of the target
products as compared to other phthalic acid derivatives.
This fact together with a large amount of substituted
phthalonitriles makes it possible to furnish symmetric and
nonsymmetric PCs with a required set of chemical, physiꢀ
cochemical, and photochemical properties depending
on the number, location, and nature of peripheral subꢀ
stituents.
Analysis of the approaches to the synthesis of PCs from
phthalonitriles allowed us to single out a group of methods
which use the reaction of phthalonitrile and its substituted
derivatives in alcohols in the presence of basic comꢀ
pounds. In this case, the intermediate products are
iminoisoindoline derivatives (1,3ꢀdiiminoisoindoline,
1ꢀalkoxyꢀ3ꢀiminoisoindolenines), which then undergo
condensation with the formation of phthalocyanine macroꢀ
heterocycle. The indicated intermediate products possess
higher reactivity in the synthesis of PCs, that is widely
used in the experimental practice, especially in the synꢀ
thesis of PCs with not very stable substituents and/or in
the preparation of nonsymmetrical PCs. The presence of
substituents in the phthalonitrile molecule influences both
the formation of the intermediate products and the subseꢀ
quent formation of the macrocycle, and it is probable that
this influence in different steps is not unambiguous.
There is no yet literature data on the quantitative evalꢀ
uation of the influence of substitution on the reactivity of
* Based on the materials of the XXVI International Chugaev
Conference on Coordination Chemistry (October 6—10, 2014,
Kazan).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1933—1941, August, 2015.
1066ꢀ5285/15/6408ꢀ1933 © 2015 Springer Science+Business Media, Inc.

1934
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 8, August, 2015
Lyubimtsev et al.
substituted phthalonitriles in the synthesis of PCs. In the
present work, we analyzed literature data on the reactivity
of substituted phthalonitriles and isoindolines, as well as
for the first time carried out kinetic studies of the reaction
of phthalonitrile and its 4ꢀnitroꢀ and 4ꢀaminoꢀsubstituted
derivatives with sodium methoxide in methanol and deterꢀ
mined regioisomeric composition of the products of this
reaction. Apart from that, we provide a comparative evalꢀ
uation of reactivity of 1,3ꢀdiiminoisoindoline and 3ꢀiminoꢀ
1ꢀmethoxyisoindolenine in the reaction with pꢀtoluidine,
which simulates an initial stage of the formation of
phthalocyanine system.
of phthalonitrile molecule leads only to the insignificant
changes in the geometrical and electronic structure.
As it was expected, electron density distribution in the
molecules of substituted phthalonitriles is considerably
more affected by substituents with more pronounced elecꢀ
tronꢀwithdrawing or electronꢀreleasing properties (Table 1).
A conclusion can be drawn that the nitrile groups in 3ꢀ and
4ꢀnitrophthalonitriles are more polar than in phthalonitrile
and its 3ꢀ and 4ꢀaminoꢀsubstituted derivatives, whereas
a substituent at position 3 of the phthalonitrile molecule
affects the charge distribution in the nitrile groups more
significantly.
Reactivity of substituted phthalonitriles in the reactions
with alkali metal alkoxides. The reaction of phthalonitrile
and its substituted derivatives with alkali metal alkoxides
in alcoholic media is based on the preparation of alkoxyꢀ
iminoisoindolenines, which are important intermediate
products in the synthesis of PCs and other macroheteroꢀ
cyclic compounds (Scheme 1).27
The absence of a unified viewpoint on the mechanism
of this reaction27—29 makes it difficult to explain effects of
substitution. We used quantum chemical methods30,31 for
theoretical studies of reactivity of phthalonitrile and its
substituted derivatives.
Results and Discussion
The authors of the work26 used quantum chemical calꢀ
culations (MOPACꢀ6 program, AM1 approximation) to
evaluate the influence of substitution on the electronic and
geometrical structure of phthalonitrile (1a) and some of
its derivatives. These data, as well as our new results on the
optimization of molecular structures of phthalonitrile (1a)
and its 3ꢀ and 4ꢀsubstituted nitro and amino derivatives
(1b—e) by the DFT/B3LYP/6ꢀ31G* method (Fig. 1),
show that the introduction of a substituent at position 3 or 4
178.4
178.4
178.6
1.163
1.433
1.162
1.162
1.163
1.163
1.433
1.432
1.433
1.432
1.433
1.163
178.5
178.5
1b
178.4
1c
1a
174.8
2.306
1.163
1.423
1.165
1.163
1.426
172.5
1.434
178.5
1.434
1.162
177.4
1d
1e
Fig. 1. Structures of phthalonitrile (1a), 3ꢀaminophthalonitrile (1b), 3ꢀnitrophthalonitrile (1c), 4ꢀaminophthalonitrile (1d), and
4ꢀnitrophthalonitrile (1e) optimized by DFT/B3LYP/6ꢀ31G* method (here and in Figs 2 and 3 bond angles are given in degrees, bond
distances in Å).

Reactivity of phthalocyanine precursors
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 8, August, 2015
1935
Table 1. Electronic charges (e) in the molecules of substituted phthalonitriles
X1
H
X2
H
C(1)
C(2)
C(7)*
C(9)*
N(8)*
N(10)*
0.028
0.028
–0.108
0.237
–0.108
0.234
–0.108
0.237
–0.098
0.232
–0.009
–0.462
–0.011
–0.464
–0.002
0.001
–0.009
–0.462
–0.025
–0.464
–0.014
–0.002
0.001
H
NH2
–0.032
0.075
H
H
H
H
OH
Cl
Br
–0.013
0.027
0.040
0.071
0.065
0.039
0.030
0.024
–0.110
–0.111
–0.111
–0.118
0.244
–0.108
–0.107
–0.113
–0.112
–0.100
0.219
–0.104
–0.111
–0.112
–0.122
0.238
–0.107
–0.106
–0.121
–0.114
–0.107
0.247
0.001
0.019
NO2
0.023
–0.451
–0.011
–0.012
0.004
–0.001
–0.030
–0.489
–0.009
0.006
–0.451
–0.012
–0.013
0.014
–0.003
–0.012
–0.469
0.004
H
H
H
H
Me
But
SO2NH2
CONH2
H
0.020
0.021
0.087
0.048
0.075
0.033
0.029
0.004
0.021
–0.068
NH2
OH
Cl
H
H
0.067
0.037
–0.067
0.033
–0.113
–0.109
–0.110
–0.111
–0.001
Br
H
H
0.029
0.020
0.056
0.102
–0.113
–0.111
0.012
0.000
NO2
–0.125
0.294
–0.118
0.247
0.047
–0.455
0.017
–0.451
* Charges above the line are calculated by AM1, under the line by DFT/B3LYP/6ꢀ31G*.
Scheme 1
–0.645
Li
0.485
177.8
176.7
0.284
–0.422
2a
–0.544
0.430
The MNDO calculations of the coordination system
(Fig. 2) showed30 that the placement of Li+ cation along
the axis of one of the C—CN fragments in phthalonitrile
leads to the additional polarization of this nitrile group, as
a result, the C atom of the indicated group becomes
Li
167.3
0.429
a strong electrophilic center. The optimization of this sysꢀ
tem by HF/6ꢀ31G* method (see Fig. 2, structure 2a) also
–0.543
indicates an additional polarization of one of the nitrile
groups of phthalonitrile with virtually unchanged characꢀ
teristics of the second nitrile group. Another pattern is
observed when the system in question is calculated by the
2b
Fig. 2. Structures of the phthalonitrile—lithium system optimized
by: HF/6ꢀ31G* (2a) and DFT/B3LYP/6ꢀ31G* (2b) methods.
Here and in Fig. 3 charges are given in e (1 e = 1.60219•10–19 C).

1936
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 8, August, 2015
Lyubimtsev et al.
DFT/B3LYP/6ꢀ31G* method (see Fig. 2, structure 2b).
In this case, the minimum energy on the potential energy
surface (PES) corresponds to the structure in which the
Li+ cation is placed between two N atoms of the nitrile
groups, with both nitrile groups of the phthalonitrile molꢀ
ecule experiencing polarization.
To sum up, based on the results of the theoretical studꢀ
ies we suggested the following mechanism for the isoindoꢀ
lenine ring construction: the formation of the addition
product of the alkali metal alkoxide molecule at one of the
phthalonitrile nitrile groups and subsequent intramolecuꢀ
lar cyclization of the addition product (Scheme 2).
When intermediate 2a (see Fig. 2) undergoes a nucleoꢀ
philic attack by the OH– anion, the minimum energy obꢀ
tained by the MNDO method corresponds to the structure 3a
(Fig. 3).30 Similar structure 3b optimized by the DFT/
B3LYP/6ꢀ31G* method was obtained in the presence of
the methoxide anion (see Fig. 3). These structures are
characterized by the deviation from linearity of the reactꢀ
ing nitrile group: the bond angle acquires the value of
126.4 (3a) and 125.1 (3b), whereas the N atom of this
group and the C atom of the second nitrile group approach
to a distance of 2.763 Å (3a) and 2.603 Å (3b).
Scheme 2
Apart from that, a noticeable deficiency of electron
density is observed on the C atom of the second nitrile
group under the influence of the positive charge of the
lithium ion, that suggests the presence of the reaction
between these atoms with the formation of a fiveꢀmemꢀ
bered cycle.
In the molecules of substituted phthalonitriles, the subꢀ
stituent conjugated with one of the nitrile groups has
a larger electronic influence on this group than on the
second one. However, as it was pointed out above, this
influence is not significant in the ground state. The influꢀ
ence of substituents on transition states (TS) and intermeꢀ
diates is much stronger, especially in the case of substitutꢀ
ed phthalonitriles. Therefore, in the framework of the sugꢀ
gested mechanism, we analyzed the influence of substituꢀ
ents on the reactivity of corresponding phthalonitriles.
Aminoꢀ and nitro groups have been chosen as substituꢀ
ents, since they possess a pronounced electronꢀreleasing
and electronꢀwithdrawing character, respectively.30,31
The analysis of critical points on the PES shows
a decrease in the activation parameters for both steps proꢀ
vided that the electronꢀwithdrawing substituents are
present in the phthalonitrile molecule and an increase in
the energy barriers in the case of 4ꢀaminophthalonitrile.
Proceeding from the difference in the Gibbs free energies
of the alternative reaction pathways of substituted phthaloꢀ
nitriles, the formation of virtually equimolar mixture of
regioisomers should be expected for 4ꢀsubstituted phthaloꢀ
nitriles, the regioisomer formed by pathway a (Scheme 3)
will predominate in the reaction mixture of 3ꢀnitrophthaloꢀ
nitrile with lithium methoxide31.
H(16)
O(15)
C(7)
C(1)
N(8)
126.4
2.763
C(2)
Li
N(10)
C(9)
3a
–0.677
125.1
Li
The calculation results agree with the experimental
data on the synthesis of diiminoisoindoline derivatives.
Thus, for example, in the work32 it was shown that the
reaction time for the formation of 5ꢀaminoꢀ1,3ꢀdiiminoꢀ
isoindoline from 4ꢀaminophthalonitrile is ~4 times longer
than that of unsubstituted compound. We noted33 that
3ꢀ and 4ꢀnitrophthalonitriles react more actively with soꢀ
dium methoxide as compared to the unsubstituted comꢀ
pound. Nitroꢀsubstituted methoxyiminoisoindolenines
2.603
0.521
167.6
3b
Fig. 3. Optimized structures of the addition products of lithium
hydroxide and lithium methoxide to phthalonitrile.

Reactivity of phthalocyanine precursors
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 8, August, 2015
1937
Scheme 3
conditions, 4ꢀaminophthalonitrile reacts with the formaꢀ
tion of the corresponding iminomethoxyisoindolenines
considerably slower as compared to unsubstituted phthaloꢀ
nitrile and its 4ꢀnitro derivative.
Kinetic studies confirm the mechanism suggested for
the reaction, while the results obtained agree with the litꢀ
erature and experimental data on the reactivity of phthaꢀ
lonitrile and its substituted derivatives toward alkali metal
alkoxides in alcoholic media. It should be noted that
a decrease in the reaction rate in the case of 4ꢀaminoꢀ
phthalonitrile is more pronounced than an increase in the
rate for 4ꢀnitrophthalonitrile.
Comparative reactivity of iminoisoindoline derivatives
and studies of regioisomeric composition of the reaction
products of substituted phthalonitriles with sodium methꢀ
oxide. Iminoisoindoline alkoxy derivatives are unique inꢀ
termediate products in the synthesis of PCs from the point
of view of their reactivity. The uniqueness of these comꢀ
pounds consists not only in their experimentally observed
higher reactivity in the reactions with nucleophilic agents
(ammonia, amines) as compared to 1,3ꢀdiiminoisoindoꢀ
line, but also in the ability to selectively (without liberaꢀ
tion of ammonia) react with these nucleophiles, giving
rise to Nꢀsubstituted iminoisoindoline derivatives. Thus,
the reaction of phthalonitrile in methanol in the presꢀ
ence of sodium methoxide with an equimolar amount of
pꢀtoluidine at room temperature leads to 3ꢀiminoꢀ1ꢀ(Nꢀpꢀ
tolylimino)isoindoline (4) (Scheme 4). Analysis of the
TLC and HPLC results showed the absence in the reacꢀ
tion mixture of 1,3ꢀbis(Nꢀpꢀtolylimino)isoindoline (5).
The latter is formed as a major product only upon a proꢀ
longed heating of the reaction mixture.
The introduction of a substituent in the phthalonitrile
molecule leads not only to the change in the reaction rate,
as was shown above by theoretical and experimental studꢀ
ies, but also to the formation of isomeric iminomethoxyꢀ
isoindolenines. However, a relative instability of alkoxy
compounds in solutions even at room temperature and
low lability of these compounds on solid supports make it
problematic to use efficient methods for the analysis of
regioisomeric composition of these compounds.
begin to form virtually immediately after the addition of
the corresponding nitrophthalonitrile to the solution of
sodium methoxide. This results is the shortening of the
reaction time to 30—45 min as compared to 90 min for
phthalonitrile.
In order to explain the experimentally observed facts,
as well as to quantitatively evaluate the reactivity of subꢀ
stituted phthalonitriles, we carried out kinetic studies of
the reactions of phthalonitrile, 4ꢀnitrophthalonitrile, and
4ꢀaminophthalonitrile with sodium methoxide in methaꢀ
nol. Figure 4 shows kinetic dependences of concentraꢀ
tions of phthalonitrile and its substituted derivatives. As it
follows from Fig. 4, all three dependences are straight
linear, which confirms a predicted pseudo first order of the
reaction in the corresponding phthalonitriles. The highest
value of rate constant is observed for 4ꢀnitrophthalonitrile.
The dependence for the unsubstituted compound occuꢀ
pies an intermediate position between kinetic dependencꢀ
es for 4ꢀnitroꢀ and 4ꢀaminophthalonitrile. Under similar
ln(C0/C)
1.8
1.6
1.4
Taking into account a specific reactivity of alkoxyꢀ
iminoisoindolines pointed out above, which consists
in the selective reaction of these compounds with amines
without formation of ammonia, the ratio of isomeric alkoxy
compounds can be determined based on the ratio of
the products of their reaction with these nucleophiles.
NꢀAryliminoisoindolines formed in the reaction with
aromatic amines are stable compounds both in the solid
state and in solutions of organic solvents and can be sucꢀ
cessfully purified and identified. We used this approach
for the studies of the regioisomeric composition of
iminomethoxyisoindolines in the reactions of 3ꢀnitroꢀ
phthalonitrile and 4ꢀnitrophthalonitrile with sodium
methoxide in methanol.
2
1.2
1.0
0.8
0.6
0.4
0.2
1
3
200 400 600 800 1000 1200 1400 t/min
Fig. 4. Kinetic curves for the reactions of phthalonitrile (1),
4ꢀnitrophthalonitrile (2), and 4ꢀaminophthalonitrile (3) with
sodium methoxide in methanol; k1 = 2.5•10–3 min–1, k2
=
= 2.1•10–2 min–1, k3 = 4.5•10–5 min–1
.

1938
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 8, August, 2015
Lyubimtsev et al.
Scheme 4
a. m = 1 equiv., ~20 C; b. m > 2 equiv., b.p.
Using HPLC, we showed that the reaction of 3ꢀnitroꢀ
phthalonitrile with sodium methoxide in the presence of
pꢀtoluidine (Scheme 5) leads to the formation of two comꢀ
pounds in the ratio ~1 : 4. Both compounds were isolated
by fractional crystallization from toluene with subsequent
recrystallization from methanol, HPLC analysis conꢀ
firmed their purity. A combination of different
methods confirmed that the reaction of 3ꢀnitrophthaloꢀ
nitrile with sodium methoxide results in the mixture of
regioisomers 6 and 7 in the ratio 4 : 1 with the predomiꢀ
nance of the reaction product at the nitrile group ortho to
the substituent. In the case of 4ꢀnitrophthalonitrile,
isomers 8 and 9 are present in the mixture in approximately
equal amounts (Scheme 6). These facts agree with the
conclusions drawn based on the reported above results of
quantum chemical calculations in the framework of sugꢀ
gested mechanism and are an additional evidence in its favor.
Reactivity of substituted iminoisoindolines. The existꢀ
ence of alkoxyiminoꢀ and diiminoisoindolines in different
tautomeric forms will influence the reactivity of these comꢀ
pounds in the synthesis of phthalocyanines and macroꢀ
heterocyclic compounds. Therefore, the consideration of
relative reactivities of different forms of alkoxy compounds
and diiminoisoindoline will make it possible to better
Scheme 5

Reactivity of phthalocyanine precursors
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 8, August, 2015
1939
Scheme 6
understand the mechanistic aspects of the macrocycle forꢀ
mation process.
noꢀ1ꢀmethoxyisoindolenine is more active in the reaction
with ammonia than 3ꢀiminoꢀ1,1ꢀdimethoxyisoindoline.
Of two tautomeric forms of 1,3ꢀdiiminoisoindoline, the
aminoisoindolenine form reacts with ammonia also more
actively than the isoindoline form. Apart from that, it was
shown that 3ꢀiminoꢀ1ꢀmethoxyisoindolenine reacts with
ammonia passing a lower activation barrier as compared
to both forms of 1,3ꢀdiiminoisoindoline. The considerꢀ
ation of the effects of temperature and solvent through the
dielectric permittivity makes it possible to determine the
optimal conditions for carrying out the reaction of the
formation of 1,3ꢀdiiminoisoindoline from 3ꢀiminoꢀ1ꢀ
methoxyisoindolenine, namely, the process should be conꢀ
ducted at low temperatures in the solvents with high diꢀ
electric permittivity.
Experimental data showed that 3ꢀiminoꢀ1ꢀ(Nꢀpꢀtolylꢀ
imino)isoindoline and its nitroꢀsubstituted derivatives are
formed from the corresponding 3ꢀiminoꢀ1ꢀmethoxyisoꢀ
indolenines considerably faster than from 1,3ꢀdiiminoꢀ
isoindoline. However, these experimental data do not allow
one to determine with certainty from which tautomeric or
isomeric form the products of the reaction in question are
formed.
In order to evaluate the reactivity of different forms of
alkoxyimino and diimino isoindoline derivatives, we carꢀ
ried out the calculations of model reactions of 3ꢀiminoꢀ1ꢀ
methoxyisoindolenine, 3ꢀiminoꢀ1,1ꢀdimethoxyisoindoꢀ
line, 1,3ꢀdiiminoisoindoline, and 1ꢀaminoꢀ3ꢀiminoꢀ
isoindolenine with ammonia as a model nucleophile
(Scheme 7).34,35 The results obtained showed that 3ꢀimiꢀ
Despite the experimental data on higher reactivity of
iminoisoindolenine methoxy derivatives as compared to
Scheme 7

1940
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 8, August, 2015
Lyubimtsev et al.
1,3ꢀdiiminoisoindoline, the quantitative characteristics of
the processes under consideration are not reported in the
literature. In this connection, we studied kinetics of the
reactions of 3ꢀiminoꢀ1ꢀmethoxyisoindolenine and 1,3ꢀdiꢀ
iminoisoindoline with pꢀtoluidine in DMF. The spectroꢀ
photometric method with the detection of the concentraꢀ
tion growth of formed 3ꢀiminoꢀ1ꢀ(Nꢀpꢀtolylimino)isoꢀ
indoline at the absorption maximum (380 nm) showed
that the rate constant of the reaction of 3ꢀiminoꢀ1ꢀmethꢀ
oxyisoindolenine with pꢀtoluidine is 4.5 times higher than
the rate constant of the reaction of 1,3ꢀdiiminoisoindoline
with the same amine (Fig. 5). This fact confirms the exꢀ
perimental data concerning the reactivity of compounds
in the case of reactions with nucleophiles (amines, amꢀ
monia), as well as the conclusions drawn based on the
results of quantum chemical calculations.
In conclusion, the theoretical and experimental studies
of the reactions of phthalonitrile and its substituted derivꢀ
atives with sodium methoxide in methanol made it possiꢀ
ble to suggest the most plausible mechanism for this reacꢀ
tion. Considering this mechanism, we evaluated the inꢀ
fluence of the nature and position of substituent in the
phthalonitrile molecule on the reaction rate and selectivity.
For the first time, kinetic measurements show the higher
reactivity of 4ꢀnitrophthalonitrile in the reaction with soꢀ
dium methoxide in methanol as compared to phthaloꢀ
nitrile (4ꢀaminophthalonitrile considerably slower forms
the corresponding methoxyiminoisoindolenines than
phthalonitrile and 4ꢀnitrophthalonitrile). Due to the speꢀ
cific ability of iminoisoindoline methoxy derivatives to
react with amines without liberation of ammonia, we studꢀ
ied the regioisomeric composition of substituted iminoꢀ
methoxyisoindolenines based on the results of the analysis
of the products of their reaction with pꢀtoluidine. Using
quantum chemical calculations and experimental kinetic
studies, we showed that 3ꢀiminoꢀ1ꢀmethoxyisoindolenine
is more active than 1,3ꢀdiiminoisoindoline in the reacꢀ
tions with nucleophilic agents (ammonia, pꢀtoluidine).
This work was financially supported by the Ministry of
Education and Science of the Russian Federation (Project
No. 795) and the Russian Foundation for Basic Research
(Project No. 13ꢀGꢀRFꢀ13).
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Received December 17, 2014;
in revised form February 12, 2015