m, 2CH). 13C NMR (CDCl3), δ (ppm): 23.7, 26.4, 31.5, 98.3,
1.81-1.83 (4Н, m, 2СН2), 2.03-2.05 (4Н, m, 2СН2), 3.04 (6Н, s,
OСН3), 6.67-6.69 (2Н, m, 2СН), 7.00-7.02 (2H, m, 2CH). 13C
NMR (CDCl3), δ (ppm): 25.3, 30.9, 47.7, 96.2, 98.0, 115.4,
130.45, 136.5. ESI-MS (m/z): 301.3 [M+Na]+. Anal. calcd (%)
for C14H18N2O4 (278.30): C 60.42; H 6.52; N 10.07. Found: С
60.49; Н 6.61; N 10.13.
ACCEPTED MANUSCRIPT
115.4, 131.3, 137.6, 174.9. MS m/z (I, %) 236 [M]+ (21), 220
(29), 161 (18), 147 (10), 130 (10). HRMS: m/z (M+) cald for
C11H12N2O4: 236.0792; found: 236.0794. Anal. calcd (%) for
C11H12N2O4 (236.22): C 55.93; H 5.12; N 11.86. Found: С 56.00;
Н 5.14; N 11.83.
4.4. Synthesis of 2-(3-methoxy-3-oxopropyl)-2-methyl-2H-
benzimidazole 1,3-dioxide (3i)
4.8. Synthesis of 4'-(hydroxyimino)spiro[benzimidazole-2,1'-
cyclohexane] 1,3-dioxide (5)
To a solution of o-benzoquinondioxime (0.7 g, 5 mmol) in
methanol (50 mL) were added levulinic acid (2.5 mL) and HClO4
(1 mL). The reaction mixture was stirred for 1 week at room
temperature. The solvent was evaporated in vacuo. The residue
To a solution of ketone (0.2 g) in water (10 mL) was added
hydroxylamine hydrochloride (0.2 g). The reaction mixture was
stirred at room temperature until disappearance of the parent
ketone (TLC), approximately 3 h. The product was extracted with
chloroform (3x10 mL), the extract was dried over magnesium
sulfate, and evaporated in vacuo to give the crude product, which
was purified by column chromatography (chloroform/methanol,
20:1), pure fractions were collected, solvents were evaporated in
vacuo to give 0.2 g (94%) of dark red powder. Mp: 122-123 °C
with decomposition. IR (KBr), ν: 746, 1097, 1311, 1403, 3232
cm–1. UV, λmax (lg ε) 249 (4.00), 515 (3.18) nm; 1Н NMR
(CDCl3), δ (ppm): 2.14-2.16 (2Н, m, СН2), 2.19-2.22 (2Н, m,
СН2), 2.81-2.84 (2Н, m, СН2), 3.09-3.11 (2Н, m, СН2), 6.91-6.93
(2Н, m, 2СН), 7.23-7.24 (2H, m, 2CH), 8.95 (1Н, br s, NОН).
13C NMR (CDCl3), δ (ppm): 17.4, 24.5, 32.1, 33.0, 95.8, 115.4,
130.9, 136.7, 155.6. MS m/z (I, %) 247 [M]+ (51), 231 (50), 230
(100), 215 (15), 214 (55), 196 (29), 145 (40). HRMS: m/z (M+)
cald for C12H13N3O3: 247.0951; found: 247.0958. Anal. calcd (%)
for C12H13N3O3 (247.25): C 58.29; H 5.30; N 16.99. Found: С
58.21; Н 5.22; N 17.03.
was
purified
by
column
chromatography
(eluent:
chloroform/methanol) to give 0.42 g (33%) of dark red oil. IR
(KBr), ν: 746, 1311, 1411, 1738 (СООСН3) cm–1. UV, λmax (lg ε)
1
248 (4.16) 516 (3.12) nm; Н NMR (CDCl3), δ (ppm): 1.56 (3Н,
s, СН3), 1.99-2.03 (2Н, m, СН2), 2.30-2.34 (2Н, m, СН2), 3.49
(3Н, s, OСН3), 6.78-6.80 (2Н, m, 2СН), 7.06-7.08 (2H, m, 2CH).
13C NMR (CDCl3), δ (ppm): 23.2, 26.4, 31.3, 51.3, 98.0, 115.1,
130.5, 138.1, 171.0. Anal. calcd (%) for C12H14N2O4 (250.25): C
57.59; H 5.64; N 11.19. Found: С 57.62; Н 5.70; N 11.26.
4.5. Synthesis of 2-(3-ethoxy-3-oxopropyl)-2-methyl-2H-
benzimidazole 1,3-dioxide (3j)
To a solution of o-benzoquinondioxime (2.76 g, 20 mmol) in
ethanol (50 mL) were added ethyl ester of levulinic acid (6.0 g)
and dropwise under stirring HClO4 (6 mL, 9.2 g, 64 mmol). This
produces a homogeneous solution. The reaction mixture was
stirred for 48 h at room temperature. The solvent was evaporated
in vacuo. The excess ethyl levulinate was removed by blowing
with air. The residue was purified by column chromatography
(eluent: ethyl acetate:hexane, 1:1) to give 3.2 g (60.6%) of red
oil. IR (KBr), ν: 1734 (С=О) cm–1. UV, λmax (lg ε) 248 (4.03),
323 (3.50), 515 (3.10) nm; 1Н NMR (CDCl3), δ (ppm): 1.15 (3Н,
t, СН3, J = 7.0 Hz), 1.65 (3Н, s, СН3), 2.05-2.09 (2Н, m, СН2),
2.39-2.43 (2Н, m, СН2), 4.01-4.05 (2Н, m, СН2), 6.84-6.86 (2Н,
m, 2СН), 7.14-7.16 (2H, m, 2CH). 13C NMR (CDCl3), δ (ppm):
13.9, 23.7, 26.8, 31.7, 60.7, 98.2, 115.3, 130.9, 137.3, 170.8.
Anal. calcd (%) for C13H16N2O4 (264.27): C 59.08; H 6.10; N
10.60. Found: С 59.13; Н 6.08; N 10.56.
4.9. Hydrolysis of 2-(3-ethoxy-3-oxopropyl)-2-methyl-2H-
benzimidazole 1,3-dioxide (3j)
To solution of compound 3j (0.53 g, 2 mmol) in water (15
mL) was added NaOH (0.2 g, 5 mmol). The reaction mixture was
stirred for 24 h at room temperature, then carefully acidified with
5% hydrochloric acid to pH 3. The product was extracted with
chloroform (5x15 mL), the extract was dried over magnesium
sulfate, and evaporated in vacuo to give the crude product, which
was purified by column chromatography (chloroform/methanol,
4:1). Pure fractions were collected, solvents were evaporated in
vacuo to give 0.34 g (72%) of compound 3h. Data matched that
previously reported.
4.6. Synthesis of 4'-oxospiro[benzimidazole-2,1'-cyclohexane]
1,3-dioxide (3k)
4.10. Synthesis of 2-(3-amino-3-oxopropyl)-2-methyl-2H-
benzimidazole 1,3-dioxide (6)
Compound 3k was prepared as described above in the general
procedure. Dark red powder. Yield 78%. Mp: 140-141 °C with
decomposition. IR (KBr), ν: 1398, 1716 (C=O) cm–1. UV, λmax (lg
To compound 3j (0.2 g) was added 30% ammonia solution (10
mL). The reaction mixture was stirred for 6 h at room
temperature. The product was extracted with chloroform (5x10
mL), the extract was dried over magnesium sulfate, and
evaporated in vacuo to give the crude product, which was
purified by column chromatography (chloroform/methanol,
10:1), pure fractions were collected, solvents were evaporated in
vacuo to give 0.92 g (84%) of dark red powder. Mp: 145-146 °C.
IR (KBr), ν: 1681 (С=О) cm–1. UV, λmax (lg ε) 248 (4.11), 516
1
ε) 248 (3.60), 515 (3.18). nm; Н NMR (CDCl3), δ (ppm): 2.33-
2.36 (4Н, m, СН2), 2.85-2.87 (4Н, m, СН2), 6.90-6.92 (2Н, m,
2СН), 7.19-7.21 (2H, m, 2CH). 13C NMR (CDCl3), δ (ppm):
32.6, 33.9, 94.4, 115.3, 131.0, 136.8, 207.0. ESI-MS (m/z): 233.2
[M+H]+, 255.2 [M+Na]+, 271.2 [M+K]+. Anal. calcd (%) for
C12H12N2O3 (232.23): C 62.06; H 5.21; N 12.06. Found: C 62.13;
H 5.29; N 11.98.
1
(3.42) nm; Н NMR (CDCl3), δ (ppm): 1.68 (3Н, s, СН3), 2.02-
4.7. Synthesis of 4',4'-dimethoxyspiro[benzimidazole-2,1'-
cyclohexane] 1,3-dioxide (4)
2.05 (2Н, m, СН2), 2.43-2.47 (2Н, m, СН2), 5.52-5.59 (2Н, m,
NН2), 6.87-6.89 (2Н, m, 2СН), 7.17-7.19 (2H, m, 2CH). 13C
NMR (CDCl3), δ (ppm): 23.7, 27.8, 32.2, 98.5, 115.3, 131.0,
137.3, 172.2. ESI-MS (m/z): 258.2 [M+Na]+, 274.2 [M+K]+.
Anal. calcd (%) for C11H13N3O3 (235.24): C 56.16; H 5.57; N
17.86. Found: C 56.23; H 5.60; N 18.02.
To a solution of ketone (0.5 g, 22 mmol) in methanol (10 mL)
was bubbled dry hydrogen chloride (0.2 g, the amount was
determined by weighing). The reaction mixture was stirred for 10
h at room temperature. The solvent was evaporated in vacuo. The
residue was purified by column chromatography (eluent:
chloroform) to give 0.48 g (80%) of purple powder. Mp: 124-126
°C. IR (KBr), ν: 746, 1047, 1099, 1110, 1407, 2945 cm–1. UV,
λmax (lg ε) 249 (4.00), 515 (3.18) nm; 1Н NMR (CDCl3), δ (ppm):
4.11. Synthesis of mixture of 4,6-dichloro-2,2-dimethyl-2H-
benzimidazole 1,3-dioxide (8) and 6,8-dichloro-3,3-dimethyl-
3H-benzo[c][1,2,5]oxadiazine 4-oxide (9)