Free radicals in vicarious C-amination reactions of 1-methyl-4- nitropyrazole

Article abstract of DOI:10.1002/mrc.1708

The primary radical anions of substrate in the reactions of vicarious nucleophilic substitution of hydrogen in 1-methyl-4-nitropyrazole with 1,1,1-trimethylhydrazinium iodide and 4-amino-1,2,4-triazole in t-BuOK-DMSO were observed and identified by EPR mo

Full text of DOI:10.1002/mrc.1708

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2005; 43: 1023–1027
Published online 19 September 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1708
Free radicals in vicarious C-amination reactions
of 1-methyl-4-nitropyrazole
Tamara I. Vakul’skaya,∗ Irina A. Titova, Gennadii V. Dolgushin and Valentin A. Lopyrev
A. E. Favorsky Irkutsk Institute of Chemistry of the Russian Academy of Sciences, Siberian Branch, Favorsky Street 1, Irkutsk, 664033, Russia
Received 2 July 2005; Revised 1 Aug 2005; Accepted 9 Aug 2005
The primary radical anions of substrate in the reactions of vicarious nucleophilic substitution of
hydrogen in 1-methyl-4-nitropyrazole with 1,1,1-trimethylhydrazinium iodide and 4-amino-1,2,4-triazole
in t-BuOK–DMSO were observed and identified by EPR monitoring. The probable mechanism of the
substrate radical anions formation is discussed. Copyright  2005 John Wiley & Sons, Ltd.
KEYWORDS: ESR; radical anions; nitropyrazoles; amination; vicarious nucleophilic substitution
the difference between the values of the standard potential
and the peak potential on the cyclic volt–ampere curve.
The decrease of the driving force leads to the change of the
mechanism of the reaction from step to concert.13–15 It is
possible to expect experimental evidence of a single electron
transfer in cases of very easily oxidizing nucleophiles and
very easily reducing electrophiles. Therefore, from the point
of view of a possible electron transfer, we are interested in
the reactions where the probability of intermediate radicals
formation is high enough, i.e. in the reactions of vicarious
nucleophilic amination of nitroazoles.
There is only one example when the authors16 have
observed the formation of radical anions in VNS of hydrogen
reaction of nitrobenzene with methyldichloroacetate, but
the authors have neither described the method by which
they registered radical anions nor have they presented their
characteristics.
INTRODUCTION
The introduction of functional groups in nitroaromatic com-
pounds via the reaction of vicarious nucleophilic substitution
(VNS) of hydrogen1,2 has greatly supplemented the arsenal
of previously accessible azoles containing both nitro and
amino groups.3 In spite of many attempts to shed light on
the mechanism of hydrogen VNS reactions,4–8 the elemen-
tary stages of this process are still poorly understood. A
universally adopted viewpoint in the literature is that the
reaction proceeds through the polar mechanism involving
the formation of intermediate ꢀH-complex.6
The VNS of hydrogen reactions requires some conditions
favoring realization of redox process: the substrate should
have a strong electron-withdrawing group (mostly NO2);
strong basic media as a contributory factor for the activation
of reactants (t-BuOK/DMSO), preferably in two-fold excess,
should be taken; the reagent should be capable of forming a
carbanion stabilized by a high basic medium.
The electron transfer reactions attract ever-increasing
attention.9–12 The electron transfer from nucleophile to
substrate is easily performed when the first has high energy
HOMO, which corresponds to the first ionization potential,
and the last has low energy, LUMO which corresponds to
the reduction potential. Otherwise, the electron transfer is an
extremely slow reaction.
It is necessary to note that nobody except us investigated
the VNS of hydrogen reactions by ESR. Therefore, we
initiated the present investigation of VNS of hydrogen
reactions of 1-methyl-4-nitropyrazole by ESR-monitoring in
order to observe the possible free radical intermediates.
RESULTS AND DISCUSSION
In the preliminary communication,17 it has been shown
that the reaction of 1-methyl-4-nitropyrazole (1) with 1,1,1-
trimethylhydrazinium iodide (2) in t-BuOK-DMSO leads
to the formation of 5-amino-1-methyl-4-nitro-pyrazole (3)
(Scheme 1):
The previous investigation of the mechanism of elec-
trochemical reduction of nitroazoles has demonstrated that
their N-alkylated derivatives form stable radical anions. But
radical anions of N-unsubstituted nitroazoles are quickly
decomposed, giving diamagnetic anions.18–20 It has been
observed that nitrogen-unsubstituted nitropyrazoles do not
undergo amination under the conditions mentioned in the
preceding text.17,21
Saveant and his team have used electrochemical methods
to investigate the reactions, where nucleophiles themselves
are weak electron donors (the case of a very slow electron
transfer from reagent to substrate). Definition of standard
potentials, RX/RXžꢀ and Nu/Nuꢀ, their internal barriers,
and kinetic constants of cleavage of radical anions allowed
the authors to show that the driving force of the reactions is
ŁCorrespondence to: Tamara I. Vakul’skaya, A. E. Favorsky
Institute of Chemistry of the Russian Academy of Sciences, Siberian
Branch, Favorsky Street 1, Irkutsk, 664033, Russia.
E-mail: vti@irioch.irk.ru
Contract/grant sponsor: Russian Academy of Sciences;
Contract/grant number: 4.1.7.
Copyright  2005 John Wiley & Sons, Ltd.

1024
T. I. Vakul’skaya et al.
Scheme 1. The VNS of hydrogen reaction of 1-methyl-4-nitro-
pyrazole (1) with 1,1,1-trimethylhydrazinium iodide (2).
It can be explained by the fact that the NH-bond in
the nitroazoles dissociates in strongly basic media, and the
value of reduction potential of the formed substrate anion is
actually shifted toward negative field.
Figure 1. The ESR spectrum recorded in the reaction of
1-methyl-4-nitropyrazole (1) with 1,1,1-trimethylhydrazinium
iodide (2) in t-BuOK/DMSO under high resolution conditions:
experimental spectrum, 30 min after the reaction start (a);
simulated spectrum (b).
The supposition, given in the preceding text, is in
agreement with the data on dinitropyrazole amination.22
Obviously, the presence of two strong withdrawing groups
in the molecule compensates the effect of the NH-bond
dissociation. This conforms also to our earlier study of the
electrochemical reduction mononitro- and dinitroderivatives
of pyrazole and 1,2,4-triazole, which indicated that the first
reduction potentials of dinitro derivatives are about 0.5 V
more positive than that for their mononitro analogs.23
The use of 4-amino-1,2,4-triazole (4) as an amina-
tion agent results not only in 5-amino-1-methyl-4-nitro-
pyrazole (3), but in another product identified as 1-methyl-
4-nitropyrazol-5-yl(1,2,4-triazole-4-yl)amine (5) (Scheme 2).
In order to obtain the detailed information on the
interaction of pyrazole nitro derivatives with amination
agents 2 and 4, the ESR-monitoring of the above reactions
has been carried out. One should keep in mind that when
the reactions are performed in an inert atmosphere (argon)
the transitory intensive blue-violet coloring of the reaction
mixtures, which rapidly turns to almost black, is observed.
Earlier we had obtained the analogous results of studying
VNS C-amination of 1-methyl-4-nitroimidazole.24
Figure 2. The ESR spectra recorded in the reaction of
1-methyl-4-nitropyrazole (1) with 4-amino-1,2,4-triazole (4) in
t-BuOK/DMSO: modulation 0.125 mT (a); modulation 0.0125
mT (b).
In the course of ESR-monitoring of the reaction mixtures
of 1 with 2 or 4 in t-BuOK/DMSO, the well-resolved
multiplets (g-factor 2.0034) are observed (Figs 1 and 2). They
arise during 10–12 min after the beginning of the reaction
and their intensities grow up to steady-state values.
The character and hyperfine structure (HFS) coupling
constants obtained by the simulation provide evidence for
the formation of primary radical anion 6 of 1-methyl-4-
nitropyrazole (1) (Figs 1 and 2(b)). HFS coupling constants
of radical anions 6 corresponds to the interaction of an
unpaired electron with three nonequivalent nitrogen atoms,
and with three equivalent and two nonequivalent protons,
(mT): 3(1N, NO2ꢁ, 2(1H, C-5), 2(1H, C-3), 4(3H, N-CH3ꢁ,
3(1N-2) and 3(1N-1). Identification of the anion radical and
assignments the HFS coupling constants were based on
the ESR spectrum of 1-methyl-4-nitropyrazole radical anion
(6) obtained independently by electrochemical reduction,19
by simulation and quantum-mechanical calculation of spin
density distribution.
The experimental HFS coupling constants (mT) and
quantum-mechanical calculated spin densities (in parenthe-
ses) are given in the formula 6.
Possible ways of free radicals formation in the investi-
gated reactions are given in Schemes 3 and 4. One could
think that radical anions of the substrate are formed at
the C–N-bond homolytical decomposition of ꢀH-complex
Scheme 2. The VNS of hydrogen reaction of 1-methyl-4-nitro-
pyrazole (1) with 4-amino-1,2,4-triazole (4).
Copyright  2005 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2005; 43: 1023–1027

Free radicals in vicarious C-amination reactions
1025
Figure 3. The ESR spectrum recorded in the reaction of 1-methyl-4-nitropyrazole (1) with surplus of 1,1,1-trimethylhydrazinium
iodide (2) in t-BuOK/DMSO (asterisks show the signals centers: *g D 2.0044 corresponds to radical cation 9; **g D 2.0034
corresponds to radical anion 6). Under low resolution conditions (a); under high resolution conditions (b); simulated spectra (c).
Scheme 3. Possible free radicals formation and their further reactions in the vicarious C-amination of 1-methyl-4-nitropyrazole by
1,1,1-trimethylhydrazinium iodide.
8, 11 (Schemes 3, 4), but quantum-mechanical calculation
(B3LYP/6–31G*) of geometrical parameters of ꢀH-complex
Unambiguous assignment of this signal presents some
difficulties, although it is clear that the origin of this signal is
connected with the aminated agent 1,1,1-trimethylhydrazini-
um iodide and was attributed to radical cation 9 (Scheme 3).
The ground for such conclusion can serve well-known
data on close structure (CH3ꢁ3NC –CžH2,26,27 which is sta-
ble at ambient temperature in single crystals and has
the same character of the hyperfine interaction and
close values of HFS constants of methyl protons. The
difference in values of HFS constants of NH-proton
in radical cation (CH3ꢁ3NC-NžH in comparison with
CH2-protons in radical cation (CH3ꢁ3NC-CžH2 may be
explained by the influence of DMSO: including the sole
molecule of dimsyl anion in calculation leads to decreas-
ing of spin density on NH-proton from ꢀ0.0636 to
ꢀ0.0082.
˚
8 has demonstrated the lengthening of N–N-bond (1.489 A
) in its hydrazine fragment in the relation to N–N-bonds
in (CH3ꢁ3NC Nꢀ H (7, 1.447 A ), as well as in the rela-
˚
25,26
˚
tion to hydrazine radical cations (9, 1.315–1.424 A ).
This means that N–N-bond must be the first to undergo
the decomposition in the formed ꢀH-complexes, but not
C–N-bond. Therefore, we think that the way of the radical
anions formation due to ꢀH-complex decomposition is of low
probability.
In agreement with this supposition is the fact that
when 1-methyl-4-nitropyrazole (1) reacts with surplus 1,1,1-
trimethylhydrazinium iodide (2) in t-BuOK/DMSO the ESR
spectrum shows superposition of two signals with different
g-factors: 2.0034 (corresponds to the radical anion substrate)
and 2.0044 (Fig. 3).
The computer simulation of the last signal adequately
reflects the experimental spectrum for the interaction of
unpaired electron with two nonequivalent nitrogen atoms,
one hydrogen atom, and with two groups of three and six
hydrogen atoms having the following constants, (mT): 3
(1N, 0.790), 3 (1N, 0.170), 2 (1H, 0.200), 4 (3H, 0.100), 7 (6H,
0.073).
We consider that protons of methyl groups in radi-
cal cation (CH3ꢁ3NC-NžH are not equivalent owing to the
same reason as in radical cation (CH3ꢁ3NC-CžH2 – because of
hindered internal rotation.26,27 Quantum-mechanical calcula-
tions of radical cation 9 indicate that in every one of the three
methyl groups two protons are almost equivalent and that
sole has higher spin density (see formula 9 in the following
text), which satisfactorily agrees with the experimental data.
Copyright  2005 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2005; 43: 1023–1027

1026
T. I. Vakul’skaya et al.
Further experiments will show whether observable
radical anions of a substrate participate in the formation
of ꢀH-complexes or whether they are formed in a parallel
proceeding reaction.
CONCLUSIONS
Thus, ESR-monitoring of the VNS C-amination reactions of
1-methyl-4-nitropyrazole allowed us to observe and identify
primary radical anions of the substrate and to propose their
possible formation mechanism. Obviously, radical anions
of 1-methyl-4-nitropyrazole are formed as a result of direct
electron transfer from anion of reactant, which is activated
by the strongly basic medium t-BuOK/DMSO. It explains
both the formation of the product 5 (Scheme 4), and the
appearance of the signal in ESR spectra of the radical cation
9 while using the surplus 2 (Scheme 3).
EXPERIMENTAL
ESR Spectra were run on a SE/X-2547 spectrometer (Poland)
in special cells in a dry argon atmosphere in carefully purified
DMSO at room temperature for some hours. Oxygen was
removed by blowing with dry argon. All reactants separately
and in combinations of 2–3 components were checked in the
absence of paramagnetism. When all the reactants in an
inert atmosphere were mixed, a transitory blue coloring
that rapidly changed to red–brown and then gradually to
black was observed. The simulated spectra were obtained
using the WINEPR SimFonia 1.25 Program (Bruker Inc.
1996). The quantum-mechanical calculations (HF/6–31G*,
B3LYP/6–31*) were carried out using GAUSSIAN 98.28
Acknowledgement
This work was supported by grant 4.1.7 of Russian Academy of
Sciences (Department of Chemistry and Sciences about materials).
Scheme 4. Possible free radicals formation and their further
reactions in the vicarious C-amination of 1-methyl-4-nitropyra-
zole by 4-amino-1,2,4-triazole.
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