Nitropyrazoles: 19. Selective nucleophilic substitution of a nitro group in 3,4-dinitropyrazoles

Article abstract of DOI:10.1007/s11172-010-0313-y

N-Substituted 3,4-dinitropyrazoles, 1,5-dimethyl-3,4-dinitropyrazole and 1-methoxy-methyl-5-methyl-3,4-dinitropyrazole, undergo nucleophilic substitution when reacted with S-, O-, and N-nucleophiles. The substitution occurs regioselectively at the 3-posit

Full text of DOI:10.1007/s11172-010-0313-y

Russian Chemical Bulletin, International Edition, Vol. 59, No. 9, pp. 1786—1790, September, 2010
1786
Nitropyrazoles
19.* Selective nucleophilic substitution of a nitro group in 3,4ꢀdinitropyrazoles
I. L. Dalinger,a I. A. Vatsadze,a T. K. Shkineva,a I. O. Kortusov,b G. P. Popova,a V. V. Kachala,a and S. A. Sheveleva
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: dalinger@ioc.ac.ru
bD. I. Mendeleev University of Chemical Engineering,
9 Miusskaya pl., 125047 Moscow, Russian Federation
NꢀSubstituted 3,4ꢀdinitropyrazoles, 1,5ꢀdimethylꢀ3,4ꢀdinitropyrazole and 1ꢀmethoxyꢀ
methylꢀ5ꢀmethylꢀ3,4ꢀdinitropyrazole, undergo nucleophilic substitution when reacted with
Sꢀ, Oꢀ, and Nꢀnucleophiles. The substitution occurs regioselectively at the 3ꢀposition, affordꢀ
ing products in good yields. Anions of Nꢀunsubstituted 3,4ꢀdinitropyrazoles, 1Hꢀ3(5)ꢀmethylꢀ
4,5(3)ꢀdinitropyrazole and 1Hꢀ4,5(3)ꢀdinitropyrazole, also react in water with Sꢀnucleophiles
with regioselective substitution of the nitro groups in the position 3(5).
Key words: pyrazole, nitro group, nitropyrazoles, 3,4ꢀdinitropyrazoles, nucleophilic substiꢀ
tution, nucleophiles, protective group.
Previously2—4 we have demonstrated that Sꢀ, Oꢀ, and
Scheme 1
Nꢀnucleophiles react with Nꢀsubstituted 4ꢀRꢀ3,5ꢀdinitroꢀ
pyrazoles to selectively replace the nitro group at the posiꢀ
tion 5. However, under rather severe conditions and when
the pyrazole position 3 is activated by an electronꢀwithꢀ
drawing group in the position 4, such as CN group, the
substitution of the nitro group at the 3ꢀposition may ocꢀ
cur.5 Notably, in the case of Nꢀsubstituted 3,4ꢀdinitroꢀ
pyrazoles in which both replaced and the second nitro
group are in the orthoꢀpositions, only few examples of
i. MeOCH2Cl, K2CO3, MeCN, 25 °C, 1 h.
nucleophilic substitution of 3ꢀNO2 are known, namely,
reactions with hydrazine6 and with aqueous ammonia with
the latter run under pressure at 190 °C (see Ref. 7). As
a next step in our studies of the modification of nitropyraꢀ
zoles, more research on the replacement of the 3ꢀNO2
group in 3,4ꢀdinitropyrazoles appeared important.
We have studied in detail the reactions of the model
dinitropyrazoles, 1,5ꢀdimethylꢀ3,4ꢀdinitropyrazole (1) and
1ꢀmethoxymethylꢀ5ꢀmethylꢀ3,4ꢀdinitropyrazole (2), with
Sꢀ, Oꢀ, and Nꢀnucleophiles. Pyrazole 1 was chosen as
a model because of its availability by a direct oneꢀstep
nitration of 1,5ꢀdimethylpyrazole.8
HMBC spectrum, spinꢀspin coupling between CH3 proꢀ
tons and CH2OCH3 protons was found at only one pyraꢀ
zole carbon (δ 143.95), and additionally, the correlation
NOESY spectrum shows spinꢀspin coupling between CH3
protons and CH2OCH3 protons, which is only possible if
the pyrazole CH3 group is in the 5ꢀposition.
Studying nucleophilic substitution reactions of nitroꢀ
pyrazole 2 is important since, as we have demonstrated
earlier,3 Nꢀmethoxymethyl group is easily removable
through acid hydrolysis, yielding Nꢀunsubstituted nitroꢀ
pyrazoles. At the same time, dinitropyrazolate anion, like
nitrite anion, is known to be a potential leaving group, so
the orientation of nucleophilic substitution in dinitropyꢀ
razole 2 cannot be predicted precisely.
Dinitropyrazole 2 was synthesized by alkylation of
3(5)ꢀmethylꢀ4,5(3)ꢀdinitropyrazole9 with methoxymethyl
chloride in acetonitrile in the presence of K2CO3.
The structure of 2 as a 3,4ꢀ rather than 4,5ꢀdinitropyrꢀ
azole derivative was assigned based on 2D correlation
We chose ethylthioglycolate, pꢀmethylꢀ, pꢀchloroꢀ
thiophenol, and pꢀchlorobenzyl mercaptan as Sꢀnucleoꢀ
philes. The reaction was run in acetonitrile at room temꢀ
perature in the presence of K2CO3 as a base. The substituꢀ
tion products formed in 65—86% yield, with the full conꢀ
1
1H—13C HMBC and H—1H NOESY techniques. In the
* For Part 18, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1739—1743, September, 2010.
1066ꢀ5285/10/5909ꢀ1786 © 2010 Springer Science+Business Media, Inc.

Nucleophilic substitution in 3,4ꢀdinitropyrazoles
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
1787
version taking 7 h for dinitropyrazole 1 and 3 h for dinitroꢀ
pyrazole 2. It should be noted that 3,4ꢀdinitropyrazoles 1
and 2 are much more reactive towards the above Sꢀnuꢀ
cleophiles compared with the isomeric 1,4ꢀdimethylꢀ3,5ꢀ
dinitropyrazole and 1ꢀmethoxymethylꢀ4ꢀmethylꢀ3,5ꢀdiꢀ
nitropyrazole that we have studied earlier. The reaction of
the latter in acetonitrile either cannot go to completion at
all or requires heating at reflux for 15 h to complete.2
It is also noteworthy that the above 3,5ꢀdinitropyrꢀ
azoles do not react with nucleophiles of the different type,
such as Nꢀ and Oꢀnucleophiles.2
As to reactions with Nꢀnucleophiles, several examples
of these, as was mentioned above, have been known beꢀ
fore. Yet the available data are clearly not sufficient to
understand the general rules of nucleophilic substitution
of the 3ꢀNO2 group. It also appeared important to characꢀ
terize the structure of the substitution products with the
modern NMR correlation techniques.
As Nꢀnucleophiles we used aliphatic amines and
hydrazines, i.e., morpholine, pyrrolidine, hexamethylene
imine, hydrazine, and methylhydrazine. The reaction was
run in refluxing isopropanol (cf. Ref. 6a), for 7 h, with
Nꢀnucleophile in a 3ꢀfold excess affording the substituꢀ
tion products in 50—76% yield. Thus we have demonꢀ
strated that the substitution of the 3ꢀNO2 group can be
successfully effected using secondary amines along with
hydrazine.
However, we have found that 3,4ꢀdinitropyrazoles 1
and 2 can react with Nꢀ and Oꢀnucleophiles, but under
more severe conditions than those needed with Sꢀnucleoꢀ
philes (Scheme 2).
The substitution pattern for reactions with Sꢀ, Oꢀ,
Nꢀnucleophiles was determined on example of compounds
4a, 6d, 8c using correlation HMBC and HSQC experiꢀ
ments. NMR spectra of nitropyrazoles are known10,11 to
contain carbon signals in the order C(3) ≥ C(5) > C(4). In
the NMR spectra of above compounds, the C(4) carbon
gives a broadened signal due to quadrupole relaxation of
the nitroꢀgroup 14N nuclei, and consequently is attached
to NO2 group. Furthermore, the cross peaks due to the
coupling of C(3) carbon with the functionalꢀgroup proꢀ
tons (SCH2CH3, OCH3, NHNH2), and the cross peaks
due to coupling of C(5) with the methyl protons in the
HMBC spectrum provide a confirming evidence for the
nucleophilic substitution of the 3 rather than 4 position.
Previously, the 4ꢀNO2 group was believed to be entireꢀ
ly unreactive towards nucleophilic substitution11,12 because
of the enhanced electron density of this position in nitroꢀ
pyrazoles, which is supported by the widely known examꢀ
ples of an electrophilic attack on the 4ꢀposition. However,
as demonstrated in our recent studies,13 in the case of
1Hꢀ3,4,5ꢀtrinitropyrazole under conditions providing forꢀ
mation of trinitropyrazolate anion, interaction with Sꢀ,
Nꢀ, Oꢀnucleophiles does occur to selectively replace the
nitro group in the 4ꢀposition.
Scheme 2
1: R = Me; 2: R = CH2OMe; 4: R = Me, R´ = Et (a), CH2CO2Et (b),
CH2C6H4Clꢀp (c), C6H4Meꢀp (d), C6H4Clꢀp (e); 5: R = CH2OMe,
R´ = Et (a), C6H4Meꢀp (b); 6: R = Me, R´ = Ph (a), 3,4ꢀMe2C6H3 (b),
CH2CF3 (c), Me (d); 7: R = CH2OMe, R´ = Ph (a), CH2CF3 (b);
NR´R″ =
(8a),
(8b),
(8c), N(CH3)NH2 (8d),
NHNH2 (8e)
Considernig the above, it seemed interesting to invesꢀ
tigate interaction of 1Hꢀ3,4ꢀdinitropyrazoles with nucleoꢀ
philes. We chose as model systems the reactions of
1Hꢀ3(5)ꢀmethylꢀ4,5(3)ꢀdinitropyrazole 3 and 1Hꢀ4,5(3)ꢀ
dinitropyrazole 9 (see Ref. 9) with Sꢀnucleophiles as the
most reactive of heteroatomic anionic nucleophiles.
The reaction was run in water in the presence of NaOH
(2 equivalents) and the appropriate thiol (1.2 equivalents),
that is, under conditions of two interacting anions, at room
temperature for 5 h. The following acidification with diꢀ
luted H2SO4 afforded substitution products 10 and 11a—c
(Scheme 3) in high yields (72—94%).
i. R´SH/K2CO3, MeCN, 25 °C, 7 h; ii. R´OH/K2CO3, MeCN,
reflux, 15 h for 6a—c, 7a,b and CH3ONa/MeOH, reflux for 6d;
iii. NHR´RІ (3 equiv), PriOH, reflux, 7 h.
We used sodium methylate, trifluoroethanol, phenol,
and 3,4ꢀdimethylphenol as Oꢀnucleophiles. The reaction
was run in acetonitrile in the presence of K2CO3 as a base,
and in methanol in the case of sodium methylate. Note
that in contrast to reactions with Sꢀnucleophiles, full conꢀ
version requires refluxing for 10—15 h and yields are in the
range 50—83%. The only exception is the reaction with
sodium methylate, in which the substitution product is
formed in a quantitative yield, probably owing to the emꢀ
ployment of a presynthesized Oꢀanion rather than having
it being generated in situ in heterophase.
The 13C NMR spectra of compounds 10 and 11a—c
contain, along with the signals from carbons of R and R´
moieties, three signals of the pyrazole carbons broadened

1788
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
Dalinger et al.
Scheme 3
(CH2); 10.62 (CCH3). IR, ν/cm–1: 1556, 1512, 1488, 1368, 1336
(NO2). MS, m/z (Irel (%)): 216 [M]+.
Interaction of 1ꢀRꢀ3,4ꢀdinitropyrazoles with Sꢀnucleophiles
(general procedure). A mixture of 1,5ꢀdimethylꢀ3,4ꢀdinitropyrꢀ
azole (1) or 1ꢀmethoxymethylꢀ5ꢀmethylꢀ3,4ꢀdinitropyrazole (2)
(2.7 mmol), the appropriate thiol (2.9 mmol), and K2CO3
(3 mmol) in acetonitrile (15 mL) was stirred vigorously for 7 h in
the case of 1 and for 3 h in the case of 2 at 20—25 °C, then
poured into water (70 mL). The precipitate that formed was
filtered off, washed with water, dried in vacuo over P2O5, and
crystallized from CCl4.
R = Me (3); R = H (9); 10: R = Me, R´ = Et; 11: R = H, R´ = Et (a); Ph
(b); pꢀMeC6H4 (c)
1,5ꢀDimethylꢀ3ꢀ(ethylthio)ꢀ4ꢀnitroꢀ1Hꢀpyrazole (4a). Yield
78%, m.p. 124—125 °C. Found (%): C, 42.11; H, 5.42; N, 21.04.
C7H11N3O2S. Calculated (%): C, 41.78; H, 5.51; N, 20.88.
1H NMR, δ: 3.70 (s, 3 H, CH3); 3.16 (q, 2 H, CH2CH3,
J = 7.1 Hz); 2.61 (s, 3 H, CH3); 1.44 (t, 3 H, CH2CH3, J = 7.1 Hz).
13C NMR, δ: 144.94 (C(3)); 142.03 (C(5)); 133.09 (C(4)); 37.20;
24.09; 14.05; 11.21. IR, ν/cm–1: 1552, 1472, 1388, 1336 (NO2).
MS, m/z (Irel (%)): 201 [M]+.
i. NaOH (2 equiv)/R´SH (1.2 equiv), H2O, 25 °C, 2 h.
due to the NH proton exchange. Application of correlaꢀ
tion HMBC, HSQC, and NOESY techniques is therefore
complicated. To exclude affecting of 13C NMR spectra by
the NH exchange, we prepared the sodium salt of pyrazole
10 by reacting 10 with MeONa (1 equivalent) in absolute
methanol followed by removing methanol in vacuo. The
13C NMR spectra of this salt show three signals with chemꢀ
ical shifts at δ 128.18, 144.97, and 146.38. Of these, the
only broadened one (due to quadrupole relaxation) is at
δ 128.18, corresponding to C(4) carbon, so the latter is
bonded to the nitro group. Additionally, in HMBC specꢀ
trum, the same atom produces the resonance featuring
a cross peak with the protons of the methyl group in the
3(5)ꢀposition. These data in combination with the abꢀ
sence of coupling between methyl and SCH2CH3 protons
in the NOESY spectrum unambiguously indicate that, as
in the case of Nꢀsubstituted 3,4ꢀdinitropyrazoles, nucleoꢀ
philic substitution occurs regioselectively at the 3(5)ꢀposiꢀ
tion, at least in reactions with Sꢀnucleophiles in water.
Ethyl[(1,5ꢀdimethylꢀ4ꢀnitroꢀ1Hꢀpyrazolꢀ3ꢀyl)thio]acetate
(4b). Yield 86%, m.p. 110—112 °C. Found (%): C, 41.80; H, 4.91;
N, 16.47. C9H13N3O4S. Calculated (%): C, 41.69; H, 5.05;
1
N, 16.21. H NMR, δ: 4.16 (q, 2 H, J = 7.2 Hz); 3.94 (s, 2 H);
3.73 (s, 3 H); 2.61 (s, 3 H); 1.23 (t, 3 H, J = 7.1 Hz). IR, ν/cm–1
:
1710 (CO); 1576, 1560, 1384, 1320 (NO2). MS, m/z (Irel (%)):
259 [M]+.
3ꢀ[(4ꢀChlorobenzyl)thio)]ꢀ1,5ꢀdimethylꢀ4ꢀnitroꢀ1Hꢀpyrazole
(4c). Yield 86%, m.p. 88—89 °C. Found (%): C, 48.59; H, 3.99;
N, 14.25. C12H12ClN3O2S. Calculated (%): C, 48.40; H, 4.06;
1
N, 14.11. H NMR, δ: 7.50 (d, 2 H, J = 8.0 Hz); 7.36 (d, 2 H,
J = 8.0 Hz); 4.30 (s, 2 H); 3.84 (s, 3 H); 2.59 (s, 3 H). 13C NMR,
δ: 144.30 (C(3)); 142.22 (C(5)); 136.55; 133.22 (C(4)); 131.75;
130.95 (CH); 128.24 (CH); 37.31; 33.05; 11.18. IR, ν/cm–1
:
1548, 1488, 1476, 1396, 1336 (NO2).
1,5ꢀDimethylꢀ3ꢀ[(4ꢀmethylphenyl)thio)]ꢀ4ꢀnitroꢀ1Hꢀpyrꢀ
azole (4d). Yield 76%, m.p. 161—162 °C. Found (%): C, 54.95;
H, 5.11; N, 16.23. C12H13N3O2S. Calculated (%): C, 54.74;
1
H, 4.98; N, 15.96. H NMR, δ: 7.47 (d, 2 H, J = 8.1 Hz); 7.22
Experimental
(d, 2 H, J = 8.1 Hz); 3.65 (s, 3 H); 2.60 (s, 3 H); 2.35 (s, 3 H).
13C NMR, δ: 144.11 (C(3)); 142.17 (C(5)); 138.81; 134.05 (CH);
1
H and 13C NMR spectra were recorded on Bruker ACꢀ300
133.29 (C(4)); 129.94 (CH); 125.28; 37.29; 20.76; 11.23. IR, ν/cm–1
1548, 1472, 1392, 1340 (NO2). MS, m/z (Irel (%)): 263 [M]+.
:
and Bruker DRXꢀ500 spectrometers, respectively in [2H6]DMSO
(unless otherwise stated) at 298 K. Chemical shifts for 1H and
13C are referred to Me4Si. IR spectra were measured on a Specord
Mꢀ80 spectrometer from KBr pellets. Mass spectra were recordꢀ
ed using a Finnigan MAT INCOS 50 instrument (direct inserꢀ
tion probe, EI, electron energy 70 eV). TLC (Silufol UVꢀ254)
was used to control reaction evolution and product purity. Eleꢀ
mental analysis was performed with a Perkin—Elmer Series II
2400 analyzer.
3ꢀ[(4ꢀChlorophenyl)thio)]ꢀ1,5ꢀdimethylꢀ4ꢀnitroꢀ1Hꢀpyrazole
(4e). Yield 65%, m.p. 147—148 °C. Found (%): C, 46.72; H, 3.67;
N, 14.98. C11H10ClN3O2S. Calculated (%): C, 46.56; H, 3.55;
1
N, 14.81. H NMR, δ: 7.62 (d, 2 H, J = 8.9 Hz); 7.50 (d, 2 H,
J = 8.8 Hz); 3.72 (s, 3 H); 2.62 (s, 3 H). 13C NMR, δ: 142.89 (C(3));
142.28 (C(5)); 135.19 (CH); 133.84; 133.40 (C(4)); 129.24 (CH);
128.21; 37.36; 11.21. IR, ν/cm–1: 1552, 1476, 1376, 1340 (NO2).
MS, m/z (Irel (%)): 283, 285 (2 : 1) [M]+.
1ꢀMethoxymethylꢀ5ꢀmethylꢀ3,4ꢀdinitroꢀ1Hꢀpyrazole (2). To
a solution of 5ꢀmethylꢀ3,4ꢀdinitropyrazole (3) (5.0 g, 0.030 mol)
in acetonitrile (200 mL) was added K2CO3 (4.5 g, 0.033 mol)
and methoxymethyl chloride (2.38 g, 0.030 mol). The mixture
was stirred for 1 h, poured into water (500 mL) and extracted
with ethyl acetate (2×70 mL). The solvent was removed in vacuo
to yield the product (5.4 g, 85%). M.p. 62—63 °C (CCl4). Found (%):
C, 33.15; H, 3.89; N, 26.12. C6H8N4O5. Calculated (%):
C, 33.34; H, 3.73; N, 25.92. 1H NMR, δ: 5.61 (s, 2 H, CH2);
3.33 (s, 3 H, OCH3); 2.66 (s, 3 H, MePz). 13C NMR, δ: 147.79
(C(3)); 143.95 (C(5)); 124.63 (C(4)); 81.38 (OCH3); 56.73
3ꢀEthylthioꢀ1ꢀmethoxymethylꢀ5ꢀmethylꢀ4ꢀnitroꢀ1Hꢀpyrazole
(5a). Yield 82%, m.p. 75—76 °C. Found (%): C, 41.74; H, 5.79;
N, 18.42. C8H13N3O3S. Calculated (%): C, 41.55; H, 5.67;
N, 18.17. 1H NMR, δ: 5.46 (s, 2 H); 3.31 (s, 3 H); 3.15 (q, 2 H,
J = 7.9 Hz); 2.65 (s, 3 H); 1.34 (t, 3 H, J = 7.9 Hz). IR, ν/cm–1
:
2964; 2928; 1552, 1484, 1396, 1344 (NO2); 1092. MS, m/z
(Irel (%)): 231 [M]+.
1ꢀMethoxymethylꢀ5ꢀmethylꢀ3ꢀ[(4ꢀmethylphenyl)thio)]ꢀ4ꢀniꢀ
troꢀ1Hꢀpyrazole (5b). Yield 78%, m.p. 82—83 °C. Found (%):
C, 53.53; H, 5.31; N, 14.54. C13H15N3O3S. Calculated (%):
C, 53.23; H, 5.15; N, 14.32. 1H NMR, δ: 7.49 (d, 2 H, J = 8.0 Hz);

Nucleophilic substitution in 3,4ꢀdinitropyrazoles
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
1789
7.23 (d, 2 H, J = 8.0 Hz); 5.34 (s, 2 H); 3.21 (s, 3 H); 2.65
(s, 3 H); 2.43 (s, 3 H). IR, ν/cm–1: 2960; 1556, 1488, 1336
(NO2); 1096. MS, m/z (Irel (%)): 293 [M]+.
4ꢀ(1,5ꢀDimethylꢀ4ꢀnitroꢀ1Hꢀpyrazolꢀ3ꢀyl)morpholine (8a).
Yield 54%, m.p. 132—133 °C. Found (%): C, 48.07; H, 6.47;
N, 25.10. C9H14N4O3. Calculated (%): C, 47.78; H, 6.24;
N, 24.77. 1H NMR (CDCl3, δ): 3.89 (m, 4 H); 3.77 (s, 3 H); 3.24
(m, 4 H); 2.56 (s, 3 H). IR, ν/cm–1: 1564, 1496, 1372, 1360
(NO2). MS, m/z (Irel (%)): 226 [M]+.
Interaction of 1ꢀRꢀ3,4ꢀdinitropyrazoles with Oꢀnucleophiles
(general procedure). A mixture of 1,5ꢀdimethylꢀ3,4ꢀdinitropyrꢀ
azole (1) or 1ꢀmethoxymethylꢀ5ꢀmethylꢀ3,4ꢀdinitropyrazole (2)
(2.7 mmol), the appropriate hydroxylꢀcontaining compound
(phenol, alcohol) (2.9 mmol), and K2CO3 (3 mmol) in acetoniꢀ
trile (15 mL) was refluxed with vigorous stirring for 15 h in the
case of 1 and for 10 h in the case of 2, then poured into water
(70 mL). The formed precipitate was filtered off, washed with
water, dried in vacuo over P2O5, and crystallized from CCl4.
1,5ꢀDimethylꢀ4ꢀnitroꢀ3ꢀphenoxyꢀ1Hꢀpyrazole (6a). Yield
83%, m.p. 119—120 °C. Found (%): C, 56.80; H, 4.84; N, 18.32.
C11H11N3O3. Calculated (%): C, 56.65; H, 4.75; N, 18.02.
1H NMR, δ: 7.39 (m, 2 H); 7.19 (m, 3 H); 3.72 (s, 3 H); 2.60
(s, 3 H). IR, ν/cm–1: 1564, 1476, 1376 (NO2); 1200. MS, m/z
(Irel (%)): 233 [M]+.
1,5ꢀDimethylꢀ4ꢀnitroꢀ3ꢀ(pyrrolidinꢀ1ꢀyl)ꢀ1Hꢀpyrazole (8b).
Yield 69%, oil. Found (%): C, 51.60; H, 6.82; N, 26.96. C9H14N4O2.
1
Calculated (%): C, 51.42; H, 6.71; N, 26.65. H NMR, δ: 3.64
(s, 3 H); 3.31 (m, 4 H); 2.54 (s, 3 H); 1.83 (m, 4 H). IR, ν/cm–1
1552, 1376, 1360 (NO2). MS, m/z (Irel (%)): 210 [M]+.
:
1ꢀ(1,5ꢀDimethylꢀ4ꢀnitroꢀ1Hꢀpyrazolꢀ3ꢀyl)azepine (8с). Yield
76%, oil. Found (%): C, 55.58; H, 7.72; N, 23.78. C11H18N4O2.
1
Calculated (%): C, 55.44; H, 7.61; N, 23.51. H NMR, δ: 3.62
(s, 3 H); 3.30 (m, 4 H); 2.53 (s, 3 H); 1.72 (m, 8 H). IR, ν/cm–1
1564, 1484, 1380 (NO2). MS, m/z (Irel (%)): 238 [M]+.
:
1,5ꢀDimethylꢀ3ꢀ(1ꢀmethylhydrazino)ꢀ4ꢀnitroꢀ1Hꢀpyrazole
(8d). Yield 52%, m.p. 111—112 °C. Found (%): C, 39.15; H, 6.20;
N, 38.32. C6H11N5O2. Calculated (%): C, 38.91; H, 5.99;
N, 37.82. 1H NMR, δ: 4.52 (br.s, 2 H); 3.73 (s, 3 H); 2.92 (s, 3 H);
2.53 (s, 3 H). 1H NMR (CDCl3, δ): 4.25 (br.s, 2 H); 3.33 (s, 3 H);
3.05 (s, 3 H); 2.62 (s, 3 H). IR, ν/cm–1: 3352; 2968; 1556, 1360
(NO2); 1220. MS, m/z (Irel (%)): 185 [M]+.
1,5ꢀDimethylꢀ3ꢀhydrazinoꢀ4ꢀnitroꢀ1Hꢀpyrazole (8e). Yield
74%, m.p. 157—158 °C (cf. Ref. 6a: m.p. 152—154 °C). 1H NMR,
δ: 7.23 (br.s, 1 H); 4.19 (br.s, 2 H); 3.66 (s, 3 H); 2.52 (s, 3 H).
13C NMR, δ: 153.74 (C(3)); 140.24 (C(5)); 118.10 (C(4));
36.47; 11.22.
Interaction of 1Hꢀ3(5)ꢀRꢀ4,5(3)ꢀdinitropyrazoles with Sꢀnuꢀ
cleophiles (general procedure). A solution of 3(5)ꢀmethylꢀ4,5(3)ꢀ
dinitroꢀ1Hꢀpyrazole (3) or 4,5(3)ꢀdinitroꢀ1Hꢀpyrazole (9)
(2 mmol) in H2O (10 mL) was treated with NaOH (4 mmol)
and after 5 min with the appropriate thiol (4 mmol), stirred
for 3 h at 20—25 °C, and acidified with 20% H2SO4 to pH 2—3.
The formed precipitate was filtered off, washed with water,
dried in vacuo over P2O5, and crystallized from EtOH—H2O
(2 : 3).
5ꢀEthylthioꢀ3ꢀmethylꢀ4ꢀnitroꢀ1Hꢀpyrazole (10). Yield 78%,
m.p. 107—108 °C. Found (%): C, 38.66; H, 4.92; N, 22.63.
C6H9N3O2S. Calculated (%): C, 38.49; H, 4.85; N, 22.44.
1H NMR, δ: 13.7 (br.s, 1 H); 3.04 (q, 2 H, J = 7.1 Hz); 2.56
(s, 3 H); 1.30 (t, 3 H, J = 7.1 Hz). 13C NMR, δ: 145.87;
142.44; 129.13; 23.62 (CH2); 14.10 (Me); 11.54 (MePz).
IR, ν/cm–1: 3376; 1568, 1480, 1376, 1348 (NO2). MS, m/z
(Irel (%)): 187 [M]+.
3ꢀ(3,4ꢀDimethylphenoxy)ꢀ1,5ꢀdimethylꢀ4ꢀnitroꢀ1Hꢀpyrazole
(6b). Yield 71%, m.p. 145—146 °C. Found (%): C, 59.92; H, 5.84;
N, 16.23. C13H15N3O3. Calculated (%): C, 59.76; H, 5.79;
N, 16.08. 1H NMR, δ: 7.15 (m, 1 H); 6.93 (s, 1 H); 6.83 (m, 1 H);
3.71 (s, 3 H); 2.62 (s, 3 H); 2.21 (s, 6 H). IR, ν/cm–1: 1560, 1480,
1396, 1340 (NO2); 1204. MS, m/z (Irel (%)): 261 [M]+.
1,5ꢀDimethylꢀ4ꢀnitroꢀ3ꢀ(2,2,2ꢀtrifluoroethoxy)ꢀ1Hꢀpyrazole
(6c). Yield 70%, m.p. 64—65 °C. Found (%): C, 35.41; H, 3.29;
N, 17.79. C7H8F3N3O3. Calculated (%): C, 35.16; H, 3.37;
1
N, 17.57. H NMR, δ: 4.95 (q, 2 H, J = 8.4 Hz); 3.71 (s, 3 H);
2.60 (s, 3 H). IR, ν/cm–1: 2960; 1568, 1364 (NO2); 1268; 1204;
1160. MS, m/z (Irel (%)): 239 [M]+.
1ꢀMethoxymethylꢀ5ꢀmethylꢀ4ꢀnitroꢀ3ꢀphenoxyꢀ1Hꢀpyrazole
(7a). Yield 57%, m.p. 71—72 °C. Found (%): C, 54.80; H, 4.89;
N, 16.15. C12H13N3O4. Calculated (%): C, 54.75; H, 4.98;
N, 15.96. 1H NMR, δ: 7.42 (m, 2 H); 7.21 (m, 3 H); 5.35 (s, 2 H);
3.37 (s, 3 H); 2.65 (s, 3 H). IR, ν/cm–1: 2988; 2932; 2832; 1564,
1484, 1380, 1368 (NO2); 1204; 1180. MS, m/z (Irel (%)): 263 [M]+.
1ꢀMethoxymethylꢀ5ꢀmethylꢀ4ꢀnitroꢀ3ꢀ(2,2,2ꢀtrifluoroethꢀ
oxy)ꢀ1Hꢀpyrazole (7b). Yield 50%, m.p. 54—55 °C. Found (%):
C, 35.93; H, 3.80; N, 15.79. C8H10F3N3O4. Calculated (%):
C, 35.70; H, 3.74; N, 15.61. 1H NMR, δ: 5.47 (s, 2 H); 4.95
(q, 2 H, J = 8.4 Hz); 3.31 (s, 3 H); 2.62 (s, 3 H). IR, ν/cm–1
:
2986; 2932; 1568, 1488, 1396 (NO2); 1268; 1204; 1162. MS, m/z
(Irel (%)): 269 [M]+.
3ꢀMethoxyꢀ1,5ꢀdimethylꢀ4ꢀnitroꢀ1Hꢀpyrazole (6d). A soluꢀ
tion of NaOMe (0.194 g, 3.6 mmol) in MeOH (10 mL) was
treated with a solution of pyrazole 1 (0.56 g, 3 mmol) in MeOH
(5 mL) at 20—25 °C. The mixture was heated at reflux for 5 h,
cooled. The precipitate that formed was filtered off and airꢀ
dried. Yield 98%, m.p. 130—131 °C. Found (%): C, 42.31;
H, 5.42; N, 24.76. C6H9N3O3. Calculated (%): C, 42.10; H, 5.30;
N, 24.55. 1H NMR, δ: 3.91 (s, 3 H); 3.69 (s, 3 H); 2.54 (s, 3 H).
13C NMR, δ: 155.86 (C(3)); 141.50 (C(5)); 117.96 (C(4)); 56.20;
36.55; 11.30. IR, ν/cm–1: 1552, 1484, 1388, 1344 (NO2). MS,
m/z (Irel (%)): 171 [M]+.
Interaction of 1ꢀRꢀ3,4ꢀdinitropyrazoles with Nꢀnucleophiles
(general procedure). A mixture of 1,5ꢀdimethylꢀ3,4ꢀdinitropyrꢀ
azole (1) (1.6 mmol) and the appropriate amine (4.8 mmol) in
isopropanol (15 mL) was refluxed for 7 h. The solvent was reꢀ
moved in vacuo. Compounds 8a, 8d, 8e were crystallized from
EtOH—H2O (2 : 3). Products 8b,c were chromatographed on
silica eluting with CHCl3—MeOH (10 : 1).
Sodium salt of 5ꢀethylthioꢀ3ꢀmethylꢀ4ꢀnitroꢀ1Hꢀpyrazole. To
a solution of NaOMe (0.108 g, 2 mmol) in absolute MeOH
(5 mL) was added pyrazole 10 (0.374 g, 2 mmol). After stirring
for 30 min at 20—25 °C, the solvent was removed in vacuo,
washed with ether, dried in vacuo over P2O5. Yield 98%,
Tdecomp 256 °C. Found (%): Na, 38.36. C6H8N3NaO2S. Calꢀ
1
culated (%): Na, 38.49. H NMR, δ: 3.00 (q, 2 H, J = 7.2 Hz);
2.32 (s, 3 H); 1.25 (t, 3 H, J = 7.1 Hz). 13C NMR, δ: 146.38;
144.97; 128.18 (C(4)); 23.38 (CH2); 14.72 (Me); 14.59 (Me).
5ꢀ(Ethylthio)ꢀ4ꢀnitroꢀ1Hꢀpyrazole (11a). Yield 72%, m.p.
73—74 °C. Found (%): C, 34.79; H, 4.12; N, 24.48. C5H7N3O2S.
1
Calculated (%): C, 34.67; H, 4.07; N, 24.26. H NMR, δ: 14.0
(br.s, 1 H); 8.86 (br.s, 1 H); 3.12 (q, 2 H, J = 7.1 Hz); 1.35
(t, 3 H, J = 7.1 Hz). 13C NMR, δ: 144.28; 132.29; 131.89; 24.24;
14.16. IR, ν/cm–1: 1560, 1472, 1376, 1340 (NO2). MS, m/z
(Irel (%)): 173 [M]+.

1790
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 9, September, 2010
Dalinger et al.
4ꢀNitroꢀ5ꢀ(phenylthio)ꢀ1Hꢀpyrazole (11b). Yield 90%, m.p.
218—219 °C. Found (%): C, 49.12; H, 3.30; N, 19.35.
C9H7N3O2S. Calculated (%): C, 48.86; H, 3.19; N, 18.99.
1H NMR, δ: 13.9 (br.s, 1 H); 8.85 (br.s, 1 H); 7.59 (m, 2 H); 7.45
(m, 3 H). 13C NMR, δ: 143.25; 133.34; 132.23; 131.61; 129.28;
128.79. IR, ν/cm–1: 1564, 1472, 1368 (NO2). MS, m/z (Irel (%)):
221 [M]+.
Chem. Bull., Int. Ed., 2009, 58, 2109]; (c) A. A. Zaitsev,
D. V. Zaiko, I. L. Dalinger, V. V. Kachala, T. K. Shkineva,
S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim., 2009, 2058 [Russ.
Chem. Bull., Int. Ed., 2009, 58, 2122].
5. I. L. Dalinger, A. A. Zaitsev, T. K. Shkineva, S. A. Shevelev,
Izv. Akad. Nauk, Ser. Khim., 2004, 553 [Russ. Chem. Bull.,
Int. Ed., 2004, 53, 580].
5ꢀ[(4ꢀMethylphenyl)thio]ꢀ4ꢀnitroꢀ1Hꢀpyrazole (11c). Yield
94%, m.p. 175—176 °C. Found (%): C, 50.86; H, 3.99; N, 18.02.
C10H9N3O2S. Calculated (%): C, 51.05; H, 3.86; N, 17.86.
1H NMR, δ: 13.8 (br.s, 1 H); 8.90 (br.s, 1 H); 7.49 (d, 2 H,
6. (a) L. I. Baryshnenkova, V. P. Perevalov, V. A. Polyakov,
Khimiya Geterotsikl. Soedinenii, 1997, 1272 [Chem. Heteroꢀ
cycl. Compd. (Engl. Transl.), 1997, 33, 1113]; (b) WO 2006/
070198 A1 (2006); Chem. Abstr., 2006, 145, 124562.
7. V. P. Perevalov, M. A. Andreeva, L. I. Baryshnenkova, Yu. A.
Manaev, G. S. Yamburg, B. I. Stepanov, V. A. Dubrovskaya,
Khimiya Geterotsikl. Soedinenii, 1983, 1676 [Chem. Heteroꢀ
cycl. Compd. (Engl. Transl.), 1983, 19, 1326].
8. M. A. Andreeva, Yu. A. Manaev, R. Ya. Mushii, V. P. Pereꢀ
valov, V. I. Seraya, B. I. Stepanov, Zh. Obshch. Khimii, 1980,
50, 2106 [J. Gen. Chem. USSR (Engl. Transl.), 1980, 50].
9. J. W. A. M. Janssen, H. J. Koeners, C. G. Kruse, C. L.
Habraken, J. Org. Chem., 1973, 38, 1777.
J = 8.1 Hz); 7.21 (d, 2 H, J = 8.1 Hz); 2.33 (s, 3 H). IR, ν/cm–1
1564, 1476, 1368 (NO2). MS, m/z (Irel (%)): 235 [M]+.
:
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Received June 9, 2010;
in revised form July 12, 2010