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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
Khisamutdinov et al.
lated (%): C, 39.80; H, 2.65; Cl, 11.77. IR, ν/cm–1: 1600, 1310
(ClC(NO2)2), 1685 (C=O), 3370 (=NOH). 1H NMR (DMSOꢀd6),
δ: 4.50 (d, 2 H, CH2, JH,H = 14 Hz); 7.15 (m, 5 H, Ph); 9.40
(s, 1 H, =NOH).
der study proceed via oximino derivatives formed upon
their reactions with nitric acid or nitrogen oxides proꢀ
duced at high temperatures, namely, via nitrolic acids.
The latter following the mechanism of oneꢀelectron transꢀ
fer from the oximate anion to the trinitromethyl group
underwent ring closure to give 3,5,5ꢀtrinitroisoxazoline
derivatives, which then transformed into 3,5ꢀdinitroisoxꢀ
azole and its derivative.
It should be noted in summary that the literature data
and the data obtained in the present work allow prediction
of the synthetic pathways toward novel isoxazole and isoxꢀ
azoline derivatives with electronꢀwithdrawing substituents
in the ring.
B. A solution of compound 1 (11 g, 0.05 mol) in glacial acetic
acid was maintained at 15—17 °C (40 mL) while a suspension of
nitrosyl sulfuric acid (prepared from sodium nitrite (10.75 g,
0.15 mol), conc. sulfuric acid (20 mL), and 18% fuming sulfuric acid
(2 mL)) was added portionwise with vigorous stirring. The reaction
mixture was kept at 15—17 °C for 40—60 min and poured onto ice.
The precipitate that formed was filtered off, washed with cold water,
and dried on air. Compound 5a was obtained in a yield of 9 g
(72%), m.p. 94—94.5 °C (CCl4). The IR spectrum of the product
was identical to that of the sample synthesized by the method A.
3ꢀAcetylꢀ5ꢀnitroisoxazole (3). A. A mixture of compound 1
(3 g, 13.5 mmol) and LiCl (0.58 g, 14 mmol, freshly calcined) in
anhydrous DMF (60 mL) was heated to 90 °C with stirring.
Evolution of nitrogen oxides and elevation of the temperature to
100 °C were observed. The reaction mixture was stirred for 2 h at
100 °C, cooled to room temperature, and poured into water
(200 mL). The mixture was extracted with diethyl ether
(2×50 mL), the combined organic layers were washed with water
(3×40 mL) and dried with MgSO4. Removal of the solvent
in vacuo and recrystallization of the solid residue from nꢀhexane
with freezing out afforded isoxazole 3 (0.5 g, 23.6%), m.p.
71—72 °C. Found (%): C, 38.47; H, 2.86; N, 17.90. C5H4N2O4.
Calculated (%): C, 38.45; H, 2.56; N, 17.93. IR, ν/cm–1: 1720
(C=O), 1600 (C=N), 1555 and 1362 (NO2). Mol. weight: found,
154 (cryoscopy in benzene); calculated, 156. 1H NMR (CD3CN),
δ: 7.30 (s, 1 H, =CH); 2.68 (s, 3 H, Me).
B. To a solution of compound 1 (3 g, 13.5 mmol) and LiCl
(0.58 g, 14 mmol) in anhydrous DMF (60 mL), N2O4 (0.86 mL,
14 mmol) was added at 5—10 °C with stirring. The reaction
mixture was stirred for 0.5 h at 5—10 °C, warmed up to 60 °C,
and kept at this temperature for 1 h. Work up as described for the
method A afforded compound 3 in a yield of 0.53 g (25%), m.p.
69—70 °C. The IR spectrum of the product was identical to that
of the sample synthesized by the method A.
C. To a solution of compound 1 (3 g, 13.5 mmol) and conc.
HCl (2 mL) in DMF (60 mL), NaNO2 (1 g, 14.5 mmol) was
added at 5—10 °C with stirring. The reaction mixture was stirred
for 30 min at 5—10 °C, then warmed up to 60 °C, and stirring was
continued for 1 h. Compound 3 was isolated as described above
(method A) in a yield of 0.57 g (26.7%), m.p. 69—71 °C. The IR
spectrum of the product was identical to that of the sample synꢀ
thesized by the method A.
Experimental
The IR spectra were recorded on a URꢀ10 spectrometer in
KBr pellets, the 1H NMR spectra were obtained on a Perꢀ
kin—Elmerꢀ12 instrument (60 MHz) relative to hexamethyldisꢀ
iloxane (internal standard).
4ꢀChloroꢀ4,4ꢀdinitroꢀ1ꢀphenylbutanꢀ1ꢀone (10). Gaseous
chlorine was passed through a stirred suspension of salt 11 (5 g,
0.02 mol) in anhydrous diethyl ether (50 mL) at 20—22 °C
until the yellow color of the starting salt disappeared. The reacꢀ
tion mixture was kept at room temperature for 2 h, the precipiꢀ
tate that formed was filtered off, the solvent from the filtrate was
removed in vacuo, the resulting product was recrystallized from
ethanol or nꢀhexane to give compound 10 in a yield of 4 g (81%),
m.p. 72—73 °C (EtOH). Found (%): C, 44.14; H, 3.41; Cl, 13.14.
C10H9ClN2O5. Calculated (%): C, 44.03; H, 3.30; Cl, 13.02. IR,
ν/cm–1: 1690 (C=O), 1595, 1310 (Cl(NO2)2C). 1H NMR
(CD3CN), δ: 3.25 (m, 4 H, CH2CH2); 7.20 (m, 5 H, Ph).
3ꢀOximino compounds 5a and 7a,b (general procedure). A.
Dry gaseous HCl and methyl nitrite generated by the known
procedure22 were passed simultaneously through a soluꢀ
tion of compound 1, 9, or 10 (0.05 mol) in anhydrous diethyl
ether (70 mL) at such a rate that the reaction mixture gently
boiled. After passage of the calculated amount of methyl nitrite,
HCl was introduced for additional 15 min, and then the reaction
mixture was kept at room temperature for 4—6 h; during this
time, the color of the reaction mixture changed from dark cherꢀ
ry to light yellow. The solvent was removed in vacuo, the reꢀ
sulting residue was recrystallized from carbon tetrachloride or
dichloroethane.
5,5,5ꢀTrinitroꢀ3ꢀoximinopentanꢀ2ꢀone (5a). The yield was
64%, light yellow crystals, m.p. 94—95 °C (CCl4). Found (%):
C, 23.83; H, 2.55; N, 22.55. C5H6N4O8. Calculated (%):
C, 24.00; H, 2.40; N, 22.40. IR, ν/cm–1: 1600, 1305 (C(NO2)3),
1720 (C=O), 3350 (=NOH). 1H NMR (DMSOꢀd6), δ: 4.20
(m, 2 H, CH2); 1.98 (s, 3 H, Me); 12.80 (s, 1 H, =NOH).
4,4,4ꢀTrinitroꢀ2ꢀoximinoꢀ1ꢀphenylbutanꢀ1ꢀone (7a). The
yield was 70%, colorless crystals, m.p. 92 °C (dichloroethane).
Found (%): C, 38.06; H, 2.45; N, 17.40. C10H8N4O8. Calculatꢀ
ed (%): C, 38.46; H, 2.56; N, 17.95. IR, ν/cm–1: 1600, 1300
(C(NO2)3), 1690 (C=O), 3365 (=NOH). 1H NMR (DMSOꢀd6),
δ: 4.15 (m, 2 H, CH2); 7.08 (m, 5 H, Ph); 10.80 (s, 1 H, =NOH).
4ꢀChloroꢀ4,4ꢀdinitroꢀ2ꢀoximinoꢀ1ꢀphenylbutanꢀ1ꢀone (7b).
The yield was 74%, light yellow crystals, m.p. 99—100 °C (CCl4).
Found (%): C, 39.16; H, 2.14; Cl, 11.48. C10H8ClN3O6. Calcuꢀ
D. To a mixture of 98% nitric acid (25 g) and water (25 mL),
compound 1 (11 g, 0.05 mol) was added in small portions at
room temperature. During addition, the reaction temperature
elevated to 30 °C. After 1 h, the reaction mixture was poured
onto ice, the precipitate that formed was filtered off, washed
with water, and recrystallized from ethanol. Compound 3 was
obtained in a yield of 0.44 g (5.6%), m.p. 70—71 °C. The IR
spectrum of the product was identical to that of the sample synꢀ
thesized by the method A.
E. A solution of compound 5a (2.5 g, 10 mmol) in 95%
MeOH (30 mL) was stirred at 30—35 °C for 2 h and the solvent
was removed in vacuo. Recrystallization of the residue from
nꢀhexane afforded compound 3 (1.09 g, 70%), m.p. 70—71 °C.
The IR spectrum of the product was identical to that of the
sample synthesized by the method A.