PAPER
Molten-State Nitration of Substituted Imidazoles
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cooled to r.t., the resulting mixture of products extracted with
CH2Cl2 (3 × 10 mL) and the organic phase dried (Na2SO4–
NaHCO3). Evaporation of the solvent gave an oil (61 mg). 1H NMR
analysis showed that the ratio of the products was 7:25:45:2:1 [cor-
responding to 1-methyl-4-nitroimidazole (5), 1-methyl-5-nitroimi-
dazole (6), 1-methyl-4,5-dinitroimidazole (8), 1-methyl-2,4-
dinitroimidazole (3), and 1-methyl-2,4,5-trinitroimidazole (1)]. The
yield of 1-methyl-2,4,5-trinitroimidazole was less than 1% based on
the integration of the 1H NMR spectrum.
Acknowledgment
The authors wish to express their thanks to Drs. Jin Rai Cho and Soo
Gyeong Cho of the Agency for Defense Development (ADD), Re-
public of Korea for their helpful cooperation in performing theore-
tical calculations.
References
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Method E (iii): Nitration of 1-Methylimidazole (4) with HNO3
and H2SO4
Reactions were performed using the same molar quantity of 1-meth-
ylimidazole (4) following essentially the same procedure as that de-
scribed in Method E (ii), except varying the concentration of the
reaction medium and time while employing LiNO3 (4.5 equiv) (see
Table 1). The yield of the desired product 1, however remained
<1%.
Method F: Nitration of 1-Methylimidazole (4) with NO2BF4
1-Methylimidazole (4) (0.77 g, 9.36 mmol) was dissolved in
MeNO2 (10 mL) and the soln cooled to –20 °C. NO2BF4 (3.0 g) was
added with vigorous stirring, and after 10 min, the cooling bath was
replaced with an oil bath (22 °C) and another portion of NO2BF4
[5.0 g (total 8.0 g, 60.0 mmol)] was added with stirring. After stir-
ring at this temperature for 1 h, the mixture was heated to 125 °C
over 1 h while MeNO2 was collected by distillation under atmo-
spheric pressure. The reaction mixture was kept at this temperature
for 1 h and then poured onto ice (200 g). The resulting product mix-
ture was extracted with CH2Cl2 (4 × 20 mL) and the combined or-
ganic phase washed successively with H2O (20 mL), 10% aq
NaHCO3 soln (20 mL) and H2O (20 mL), and then dried (Na2SO4).
Evaporation of the solvent gave an oil (0.945 g). 1H NMR analysis
indicated that the yields of 1-methyl-4,5-dinitroimidazole (8), 1-
methyl-2,4,5-trinitroimidazole (1), and 1-methyl-2-nitroimidazole
(7) were about 37%, 13% and 6%, respectively.
Method G: Nitration of 1-Methylimidazole (4) with NO2OTf
This experiment was conducted using the same procedure and mo-
lar quantities as those used in method F except that NO2OTf was
used instead of NO2BF4. After work-up, and silica gel column chro-
matographic purification (eluent: 20% EtOAc–hexane), compound
1 was obtained as a pale-yellow solid in 30% yield.
Method H: Nitration of 1-Methyl-4-nitroimidazole (5) with
NO2OTf
A soln of 1-methyl-4-nitroimidazole (5) (0.42 g, 3.31 mmol) and
NO2OTf (1.58 g, 8.10 mmol) in MeNO2 (2 mL) was heated at 95 ºC
in an oil bath. After 2.5 h, an aliquot of the reaction mixture was an-
alyzed by 1H NMR spectroscopy. Integration of the spectrum indi-
cated the formation of only two products, 1-methyl-4,5-
dinitroimidazole (8) and 1 in a ratio of ca. 3.5:2.4. The mixture was
cooled to r.t. and diluted with CH2Cl2 (50 mL). The organic layer
was washed with 10% aq NaHCO3 soln (25 mL), H2O (25 mL) and
brine (25 mL), then dried (Na2SO4) and filtered. The filtrate was
evaporated to yield a crude product (230 mg), which was subjected
to silica gel column chromatography (eluent: 20% EtOAc–hexane).
Pure product 1 was isolated in 38% yield. Prolonged heating beyond
the time mentioned resulted in decreased yields of 1.
Applications; Springer: New York, 2009. (c) Albright, L.
F.; Carr, R. V. C.; Schmitt, R. J. Nitration: Recent
Laboratory and Industrial Developments, ACS Symposium
Method I: Nitration of 1-Methyl-4-nitroimidazole (5) with
NO2BF4
This experiment was conducted using the same procedure and mo-
lar quantities as those used in method H except that NO2OTf was re-
placed with NO2BF4. Compound 1 was obtained in 4.5% yield.
Synthesis 2011, No. 17, 2859–2864 © Thieme Stuttgart · New York