Change in regioselectivity in the monoreduction of 2,4,6-trinitrotoluene with titanium(III) and vanadium(II) ions in the presence of iron(II) and copper(II) salts

Article abstract of DOI:10.1007/s11172-005-0381-6

Small additives of iron(II) or copper(II) salts change the regioselectivity of 2,4,6-trinitrotoluene monoreduction with titanium(III) chloride affording predominantly less accessible 2-amino-4,6-dinitrotoluene over 4-amino-2,6-dinitrotoluene (from 25% when the reduction occurs in the absence of the iron and copper salts to 70% in the presence of these salts). A possible mechanism of the process is discussed.

Full text of DOI:10.1007/s11172-005-0381-6

Russian Chemical Bulletin, International Edition, Vol. 54, No. 5, pp. 1203—1207, May, 2005
1203
Change in regioselectivity in the monoreduction of 2,4,6ꢀtrinitrotoluene
with titanium(III) and vanadium(II) ions in the presence
of iron(II) and copper(II) salts*
ꢀ
V. N. Leibzon, L. V. Michalchenko, M. Yu. Leonova, and V. P. Gultyai
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: guvp@ioc.ac.ru
Small additives of iron(II) or copper(II) salts change the regioselectivity of 2,4,6ꢀtrinitroꢀ
toluene monoreduction with titanium(III) chloride affording predominantly less accessible
2ꢀaminoꢀ4,6ꢀdinitrotoluene over 4ꢀaminoꢀ2,6ꢀdinitrotoluene (from 25% when the reduction
occurs in the absence of the iron and copper salts to 70% in the presence of these salts).
A possible mechanism of the process is discussed.
Key words: 2,4,6ꢀtrinitrotoluene, monoreduction, 2ꢀaminoꢀ4,6ꢀdinitrotoluene, 4ꢀaminoꢀ
2,6ꢀdinitrotoluene. regioselectivity, titanium(III), vanadium(II), iron(II), copper(II).
2ꢀAminoꢀ2,6ꢀdinitrotoluene (1) and 4ꢀaminoꢀ4,6ꢀ
dinitrotoluene (2) are the promising substrates for organic
synthesis due to the simultaneous presence of the amino
and nitro groups. Therefore, it is necessary to develop
selective methods of their synthesis, one of which is the
regioselective reduction of 2,4,6ꢀtrinitrotoluene (TNT).1
This problem is also of interest from the viewpoint of a
principal problem in organic chemistry: to elucidate facꢀ
tors affecting the regioselectivity of partial reduction of
aromatic polynitro compounds (PNC).
In our previous study, we described2 the direct elecꢀ
trochemical monoreduction of TNT to form isomeric
dinitro(hydroxyamino) derivatives and considered the
mechanism and factors that result, possibly, in similar
regioselectivity of the electroreduction and monoreducꢀ
tion by trivalent titanium and bivalent vanadium ions.
In the earlier works on studying of effect of different
factors on the regioselectivity (except for the works3,4
where the authors attempted to explain the role of comꢀ
ponents of the medium in determination of the direction
of reduction of some aromatic PNC), the reducing agents,
which are reactive toward the paraꢀ or orthoꢀnitro groups,
were usually selected5 for the preparation of some aroꢀ
matic nitroamines. For instance, the tin(II) salts reduce
more actively the oꢀnitro groups of TNT6 and, on the
contrary, the titanium(III) salts are more active in the
reduction of the pꢀnitro group.7 In the catalytic hydrogeꢀ
nation of aromatic PNC in the presence of iron powder,
as in the case of tin(II), the monoreduction of the oꢀnitro
groups proceeds more easily.8
We have previously9,10 found that the reduction of
aromatic monoꢀ and polynitro compounds, including
TNT, by the titanium(III) salts, is accelerated in the presꢀ
ence of bivalent iron and bivalent copper ions, for exꢀ
ample, by 2 and 8 times in the presence of FeSO4 in
concentrations of 0.01 and 0.3 mol L–1, respectively. In
this case, the concentration of the titanium(III) salts was
1 mol L–1. The introduction of nickel, chromium, vanaꢀ
dium, and alkalineꢀearth metal cations into the reaction
mixture has no noticeable effect on the reduction rate of
TNT by the titanium(III) ions. Thus, the influence of the
iron(II) and copper(II) ions on this process is specific.
When assuming that the catalytic effect of the iron(II)
and copper(II) ions on PNC reduction is caused by the
formation of complexes of these ions with the starting
compound or its radical anions (RA) generated after an
electron was transferred to the substrate, then one can
expect a change in the regioselectivity of the process in
the presence of these ions. This assumption is based on
published data,3,4,7,11 which show that the regioselectivity
of PNC reduction is caused by the charge and unpaired
electron density distribution in the RA. This distribution
determines the predominant direction of protonation and,
as a consequence, formation of a particular isomer by
partial reduction. A similar approach was used in the quanꢀ
tum chemical study of the regioselectivity of aromatic
PNC reduction.12 The formation of an RA complex with
metal ions can change significantly the electron density
distribution and direction of RA protonation. To check
this assumption, we carried out experiments on the partial
* Dedicated to Academician N. K. Kochetkov on the occasion
of his 90th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1172—1176, May, 2005.
1066ꢀ5285/05/5405ꢀ1203 © 2005 Springer Science+Business Media, Inc.

1204
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 5, May, 2005
Leibzon et al.
aboveꢀdescribed procedure. 2ꢀAminoꢀ4,6ꢀdinitrotoluene (1) and
4ꢀaminoꢀ2,6ꢀdinitrotoluene (2) were synthesized in an overall
yield of 85—95% with respect to the reacted TNT.
reduction of TNT by titanium(III) ions in the presence of
iron(II) and copper(II) ions.
The prepared mixtures of products were analyzed by
1H NMR spectroscopy and TLC on Sorbfil plates with the UV
indicator in a hexane—ether (1 : 4) system. 1H NMR spectra
were recorded in (CD3)2CO on a Вruker ACꢀ200 spectrometer.
The spectrum of compound 1 exhibits a characteristic singlet at
δ 7.78. That of compound 2 has a characteristic singlet at δ 7.35.
The content of each component in a mixture was determined
from integral intensities of the corresponding signals of 1,3,5ꢀtriꢀ
nitrobenzene used as an internal standard.
Experimental
Reduction of TNT was carried out using an aqueous acidic
(HCl concentration 6—8%) solution of TiCl3. This solution was
prepared by the electrochemical reduction of TiCl4 (specialꢀ
purity grade) conducted in the galvanostatic mode on a lead
electrode with a current of 1.0 A (platinum served as an anode,
and the anolyte was 7% Н2SO4). The Ti3+/Ti4+ ratio was poꢀ
larographically monitored during electrolysis. The concentraꢀ
tion of Ti3+ ions was determined by titration with a standard
solution of potassium bichromate using diphenylamine as the
indicator.
Partial reduction of TNT in the absence of iron or copper
salts. A solution of TNT (1 g) in MeOH (100 mL) was rapidly
mixed with an aqueous solution of a reagent (10 mL) containing
ТiCl3 (0.7—1.6 mol L–1) and НСl (1.5—2.0 mol L–1). The acidꢀ
ity of the medium was provided by the addition of concentrated
HCl (6 mL) to a methanolic solution of the substrate. Several
minutes after mixing, the reaction soup gained a bright yellow
color. Methanol was removed under reduced pressure, water
(50 mL) was added, and extraction with CHCl3 (3×30 mL) was
performed. Then, the aqueous layer was treated with concenꢀ
trated NH4OH to achieve pH 8—9 and again extracted with
CHCl3. The chloroform extracts were combined, washed with
water, and concentrated. In some cases, the extracts from acidic
and alkaline media were studied separately.
Results and Discussion
Iron(II) ions in a concentration of 0.001 mol L–1 and
higher change substantially the regioselectivity of TNT
monoreduction by the titanium(III) ions toward the preꢀ
dominant formation of the 2ꢀamino derivative (Scheme 1).
The content of isomer 1 in a mixture of products after
reduction increases from 25 to 50% at a concentration of
FeSO4 of 0.0023 mol L–1. For the further increase in
FeSO4, the fraction of 1 reaches a limiting value equal
to 60% (Fig. 1, curve 1). A similar but lower effect was
detected in the case of TNT monoreduction with vanaꢀ
dium(II) in the presence of iron(II) ions (see Fig. 1,
curve 2).
The change in regioselectivity observed is not due to
the effect of the iron salt as a reducing agent, because the
Fe3+/Fe2+ system has a much higher redox potential
(+0.77 V) than the Ti4+/Ti3+ pair (–0.04 V). In control
entries, the TNT conversion in the presence of excess
FeSO4 is only 10% within a week, while with the titaꢀ
nium(III) ions the reaction completes for 20 s.
Monoreduction of TNT by vanadium(II) was carried out
similarly.
Partial reduction of TNT in the presence of iron or copper
salts. Salt FeSO4 (0.008—0.016 mol L–1
)
or CuCl2
(0.003—0.0245 mol L–1) was added to a solution of ТiCl3,
and further the reaction was carried out according to the
Scheme 1
a. 1 : 2 = 1 : 3; b. 1 : 2 = 2 : 1 (for M = Fe)

Regiomonoreduction of 2,4,6ꢀtrinitrotoluene
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 5, May, 2005
1205
Y (%)
Y (%)
1
60
60
50
2
40
40
20
30
5
10
15 [CuCl2]•10–3/mol L–1
2
4
6
8
[FeSO4]•10–3/mol L–1
Fig. 2. Relative content of 2ꢀaminoꢀ4,6ꢀdinitrotoluene (1) (Y )
in mixture 1—2 for the partial reduction of TNT (С =
0.04 mol L–1) with ТiCl3 vs. CuCl2 concentration in a reaction
mixture (85 vol.% МеОН) containing 3% НСl (concentration
of ТiCl3 0.09 mol L–1, TNT conversion 30—50%, 20—25 °С).
Fig. 1. Relative content of 2ꢀaminoꢀ4,6ꢀdinitrotoluene (1) (Y )
in mixture 1—2 for partial TNT reduction (С = 0.04 mol L–1) by
TiCl3 (1) and VCl2 (2) vs. FeSO4 concentration in the reaction
mixture (85 vol.% МеОН) containing 3% НСl (concentrations
of ТiCl3 and VCl2 0.1 and 0.07 mol L–1, respectively; TNT
conversion 30—50%; 20—25 °С).
case, regioselectivity increases to a greater extent than
in the reaction with FeSO4: its content increases
from 25 to 70%.
The general character of this activation of the oꢀnitro
groups by the iron salts was confirmed by a similar reacꢀ
tion of 2,4ꢀdinitrochlorobenzene. In the presence of
FeSO4 (0.609 mol L–1) and keeping other conditions unꢀ
changed, the content of forming 2ꢀaminoꢀ4ꢀnitrochloroꢀ
benzene increased from 31 to 54% (at 30% conversion of
dinitrochlorobenzene).
The use of TiCl3 together with iron salts for a quantiꢀ
tative analysis of some nitramines (nitroguanidine, cycloꢀ
trimethylenetrinitramine) and for the stoichiometric reꢀ
duction of organic derivatives of nitric acid is indicated in
literature.13—16 A reason for the positive influence of the
iron(II) ions on the extent of reduction is considered only
in one work.15 Iron(II) ions were suggested15 to interact
with hydrolytically unstable (hydroxyamino)guanidine
formed intermediately from nitroguanidine to produce a
more stable complex ion, which is further reduced with
the titanium(III) ions. A high excess of the iron salt is used
in the analysis and, most likely, the function of the iron
ions in the reduction process is not catalytic. In the case
of aromatic PNC, no hydrolytically unstable prodꢀ
ucts are formed, and PNC cannot be reduced via this
mechanism.
It has previously17 been shown that the barium(II) and
aluminum(III) polycharged ions increase the yield of
2ꢀaminoꢀsubstituted 4ꢀnitroꢀ and 4,6ꢀdinitrobenzoic acꢀ
ids in the monoreduction of 2,4ꢀdinitrobenzoic and
2,4,6ꢀtrinitrobenzoic acids by TiCl3. This effect can be
explained17 by the formation of a complex between the
ionized carboxyl group of RA and polycharged cations or
a chelate involving both the oꢀnitro group and ionized
carboxyl group and metal cations. As indicated above,
alkaliꢀearth metal cations have no effect on the reduction
rate of TNT by the titanium(III) ions. The preparative
reduction of TNT with the titanium(III) ions in the presꢀ
ence of the barium salt showed that the barium(II) ions
did not affect the regioselectivity of the process. Thus, the
considered phenomenon differs from the described interꢀ
pretation of reduction of nitrobenzoic acids.
Three mechanisms can be responsible for a change in
the regioselectivity of reduction of aromatic PNC by the
titanium(III) and vanadium(II) salts in the presence of
iron(II) or copper(II) ions.
I. Intermediate formation of binuclear complexes,
whose reactivity is higher than that of the starting reacꢀ
tants, due to the reaction of TiCl3 and FeCl2 (or CuCl2).
However, the redox potential of the Ti3+/Ti4+ system
remains unchanged when an iron salt is introduced,
which excludes the acceleration of aromatic PNC reꢀ
duction by the titanium(III) ions in the presence of low
concentrations of the iron(II) or copper(II) ions via this
mechanism. In addition, ions with a higher oxidation
state are characterized by the formation of polynuclear
complexes.
II. Formation of a complex between metal ions and
RA of nitro compounds generated by the electron transfer
from the titanium(III) ion to the substrate. In this case,
the distributions of a charge and lone electron spin denꢀ
sity in the RA should change. These parameters are
known4 to determine the direction of RA protonation
reactions and, as a consequence, regioselectivity of the
process. In a more general form, the formation of a comꢀ
plex between an RA and М2+ ion changes the reactivity of
the RA at two reaction centers. For instance, the pꢀnitro
group as a less sterically hindered center is predominantly
involved in complex formation, and protonation proceeds
In the presence of CuCl2, as in the case of FeSO4, the
reaction between the titanium(III) salt and TNT is accelꢀ
erated and the content of orthoꢀisomer 1 in the reacꢀ
tion mixture increases remarkably (Fig. 2). In this

1206
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 5, May, 2005
Leibzon et al.
mainly at the free oꢀnitro group of the RA, which should
increase the content of isomer 1 over 2.
the acceleration of the reaction and its regioselectivity.
Therefore, we believe that the acceleration of the process
can be related to the formation of a complex of the nitro
compound with metal ions and their higher reduction rate
(mechanism III), and the change in regioselectivity is
caused by the reaction occurrence via mechanisms II and
(in part) III. A higher complexing ability of an RA comꢀ
pared to neutral nitro compounds should result in a change
in regioselectivity at rather low concentrations of metal
ions when their influence on the kinetics of the process is
relatively low.
III. Formation of a complex between a metal ion and
the starting nitro compound. In this case, the electron
transfer to this complex produces the same complex
RA•М2+ as that via mechanism II after complex formaꢀ
tion of the RA with metal ions. Mechanisms II and III are
presented in Scheme 1 for TNT, where M2+ is a metal ion
(iron(II) or copper(II)), and the reaction products are mixꢀ
tures of isomers 1 and 2 of different compositions formed
by the protonation of the RA and RA complexes with the
metal ions, respectively.
Finally, we would like to mention an analogy of the
phenomenon considered to the reduction of PNC by hyꢀ
drazine hydrate or using catalytic hydrogenation. In the
absence of iron compounds, the reduction of
aromatic PNC using these methods affords mainly
paraꢀisomers,18,19 whereas the amount of orthoꢀisomers
increases sharply in the presence of iron hydroxide or iron
salts.18 As shown above, the copper salt exerts a similar
effect on the regioselectivity of reduction by the titaꢀ
nium(III) ions. However, this effect is stronger than in the
case when the iron salt is used. Although the mechanisms
of the compared methods differ, the orthoꢀorienting inꢀ
fluence of the copper compounds on catalytic hydrogenaꢀ
tion or reduction by hydrazine cannot be excluded.
To conclude, we found that the regioselectivity of TNT
reduction with titanium(III) or vanadium(II) ions in
the presence of the iron(II) salts can be varied in a wide
range.
According to Scheme 1, an increase in the concentraꢀ
tion of the bivalent metal ions in a solution should be
accompanied by an increase in the concentration of RA
complexes with such cations, whose protonation yields a
mixture of isomers with a higher content of compound 1.
The curves of the dependence of the isomeric composiꢀ
tion of the reduction products on the metal ion concenꢀ
tration reach a limit (see Figs 1 and 2) corresponding to
the predominant occurrence of the process via route b.
A change in the regioselectivity of reduction is much more
sensitive to the presence of iron(II) ions in the solution
than the acceleration of the process by these ions. In
particular, the isomeric composition of the reduction
products of TNT by the titanium(III) ions stops deꢀ
pending on the concentration of the latter exceeding
0.01 mol L–1 (see Fig.1, curve 1). At the same time, for a
given concentration of the iron ions, the process rate
increases twofold, while the 6—8ꢀfold acceleration of the
reduction needs very high concentrations of the iron ions:
This work was financially supported by the Division of
Chemistry and Materials Sciences of the Russian Acadꢀ
emy of Sciences.
0.2—0.3 mol L–1 9,10
This difference in character of the
.
dependence of the reduction acceleration and regioꢀ
selectivity of the process on the metal ion concentration
can indicate differences in mechanisms of these pheꢀ
nomena.
References
1. S. A. Shevelev, A. Kh. Shakhnes, B. I. Ugrak, and S. S.
Vorob´ev, Synth. Commun., 2001, 31, 2557.
2. V. N. Leibzon, A. P. Churilina, M. Yu. Leonova,
L. V. Mikhal´chenko, and A. Kh. Shakhnes, Elektrokhim.,
2000, 36, 190 [Russ. J. Electrochem., 2000, 36 (Engl.
Transl.)].
3. I. I. Bilkis and V. D. Shteingarts, Zh. Org. Khim., 1982, 18,
359 [J. Org. Chem. USSR, 1982, 18 (Engl. Transl.)].
4. I. I. Bilkis, V. V. Goidin, S. I. Uskov, and V. D. Shteingarts,
Zh. Org. Khim., 1991, 27, 24 [J. Org. Chem. USSR, 1991, 27
(Engl. Transl.)].
5. A. T. Nielsen, R. A. Henry, W. P. Norris, R. A. Atkins,
D. W. Moore, and A. H. Hepil, J. Org. Chem., 1979,
44, 2499.W
6. R. Schroter and F. Moller, in Methoden der Organischen
Chemie (HoubenꢀWeil), Georg Thieme Verlag, Stuttgart—
New York, 1957, 11, Teil 1, 474.
7. I. I. Bilkis, S. I. Uskov, and V. D. Shteingarts, Izv. Sib. Otd.
Akad. Nauk SSSR, Ser. Khim. [Bull. Siberian Branch Acad.
Sci. USSR], 1987, 3, 111 (in Russian).
The reactions of TNT (or its complex with metal ions)
with the titanium(III) ions are presented in Scheme 1 as
irreversible, although the redox electron transfer processes
can be reversible. In our opinion, under the experimental
conditions (acidic aqueousꢀalcohol solutions), protonaꢀ
tion rates of RA (or their complexes) are so high that their
concentration in a solution is very low, and these reacꢀ
tions should be virtually irreversible. However, in this
case, the acceleration of reduction via mechanism II canꢀ
not be explained, because RA complexes with metal ions
are formed after the irreversible reaction. At the same
time, the complex formation of a nitro compound with
metal ions followed by the electron transfer via mechaꢀ
nism III makes it possible to explain both the acceleration
of reduction and the change in regioselectivity of the proꢀ
cess in the presence of the iron(II) or copper(II) ions.
However, this mechanism does not explain the aforeꢀ
mentioned difference in influence of the metal ions on

Regiomonoreduction of 2,4,6ꢀtrinitrotoluene
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 5, May, 2005
1207
8. G. Theodoridis, M. Manfredi, and J. Krebs, Tetrahedron
Lett., 1990, 31, 6141.
14. R. P. Zimmerman and E. Lieber, Anal. Chem., 1950,
22, 1151.
9. V. N. Leibzon, L. V. Michalchenko, M. Yu. Leonova, and
V. P. Gultyai, Abstrs Electrochemical Society 197th Meeting
(Toronto, May 14—18, 2000), Toronto, 2000, 1, Abstract
No. 1069.
10. V. N. Leibzon, L. V. Michalchenko, M. Yu. Leonova, and
V. P. Gultyai, in New Directions in Organic Electrochemistry,
Eds A. Fry and Y. Matsumura, The Electrochemical Sociꢀ
ety, Inc., Pennington, USA, 2000, 15, 60.
11. S. I. Uskov, I. I. Bilkis, and V. D. Shteingarts, Zh. Org.
Khim., 1991, 27, 36 [J. Org. Chem. USSR, 1991, 27 (Engl.
Transl.)].
12. S. E. Barrows, C. J. Cramer, D. G. Truhlar, M. S. Elovit,
and E. J. Weber, Environ. Sci. Technol., 1996, 30, 3028.
13. D. L. Kouba, R. C. Kicklighter, and W. W. Becker, Anal.
Chem., 1948, 20, 948.
15. W. W. Brandt, J. E. de Vries, and E. S. Gantz, Anal. Chem.,
1955, 27, 392.
16. W. I. Awad and S. S. M. Hassan, Talanta, 1969, 16, 1383.
17. I. I. Bilkis, S. I. Uskov, and V. D. Shteingarts, Zh. Org.
Khim., 1991, 27, 1922 [J. Org. Chem. USSR, 1982, 27 (Engl.
Transl.)].
18. H. M. Colquhoun, J. Holton, D. J. Thompson, and M. V.
Twigg, New Pathways for Organic Synthesis. Practical Appliꢀ
cations of Transition Metals, Plenum Press, New York, 1984,
400 pp.
19. N. R. Ayyangar, U. R. Kalkote, A. J. Lugade, P. V. Nikrad,
and V. K. Sharma, Bull. Chem. Soc. Jpn, 1983, 56, 3159.
Received November 26, 2004;
in revised form March 1, 2005