1452
S. Rádl, O. Klecán and J. Havlícˇek
Vol 43
ice bath. The solution of peracetic acid (40 mmol) in water (10
mL) was added dropwise over 20 min and the mixture was
stirred at ambient temperature for 20 h. The organic layer was
separated, washed with saturated aqueous potassium hydrogen-
carbonate and dried with magnesium sulfate. The residue was
separated by flash chromatography on silica (dichloromethane –
methanol – triethylamine, 100:5:1) afforded 1.26 g (33.5 %) of 9
and 0.72 g (18.4 %) of 10.
8.5 mmol) in acetonitrile (500 mL). After 2 hours of stirring at
ambient temperature the solvent was evaporated, the residue was
partitioned between dichloromethane and water (100 mL/100
mL), the aqueous layer was extracted with dichloromethane (2 x
50 mL) and the combined organic layers were dried with
magnesium sulfate. The residue after evaporation (6.4 g) was
crystallized from acetone to give 3.0 g (46 %) of 13. Mp = 149-
1
150 °C; H nmr (CDCl3): ꢀ 2.10 (m, 2H, CH2), 2.33 (s, 3H,
1
Compound 9: M. p. = 158-160 °C; H nmr (CDCl3): ꢀ 2.06
CH3), 3.34 (s, 3H, OCH3), 3.53 (t, 2H, CH2, J = 5.9), 4.11 (t, 2H,
CH2, J = 6.2), 4.76 (s, 2H, CH2), 6.77 (d, 1H, aromat. H, J =
7.3), 7.12-7.17 (m, 2H, aromat. H), 8.22 (d, 1H, aromat. H, J =
7.3), 14.20 (bs, 1H, NH); 13C nmr (DMSO-d6, 120 °C): ꢀ 10.79,
27.73, 28.40, 57.34, 66.14, 68.10, 108.23, 113.39, 120.79,
123.67, 136.57, 139.63, 147.14, 149.81, 154.61; ms, m/e: 359,13
(M+, 100.0%), 360.13 (21.5%), 361.13 (5.5%), 361.14 (1,9%);
UV (MeOH), ꢁmax (log ꢂ): 274.8 (4.30), 213.8 (4.60).
(m, 2H, CH2), 2.34 (s, 3H, OCH3), 3.36 (s, 3H, CH3), 3.56 (t,
2H, OCH2, J = 6.0), 4.08 (t, 2H, OCH2, J = 6.0), 5.08 (s, 2H,
CH2S), 6.73 (d, 1H, H-5, J = 5.9), 7.25 (m, 2H, aromat. H), 7.56
(bs, 2H, aromat. H), 8.18 (d, 1H, H-6, J = 5.9), 12.90 (bs, 1H,
1
NH); H nmr (DMSO-d6): ꢀ 1.96 (m, 2H, CH2), 2.36 (s, 3H,
OCH3), 3.22 (s, 3H, CH3), 3.48 (t, 2H, OCH2, J = 6.0), 4.08 (t,
2H, OCH2, J = 6.0), 5.08 (s, 2H, CH2S), 6.94 (d, 1H, H-5, J =
6.0), 7.38 (m, 2H, aromat. H), 7.70 (m, 2H, aromat. H), 8.04 (d,
1H, H-6, J = 5.9); 13C nmr (DMSO-d6, 120 °C): ꢀ 10.71, 17.05,
28.03, 57.42, 67.81, 68.93, 107.80, 107.98, 119.77, 123.41,
124.95, 129.55, 137.21, 143.46, 145.23, 153.27, 162.65; IR:
2990-2855, 1461 (CH3, CH2, CH), 3140-3000, 1500-1455, 775-
735 (Arom.), 1584, 1365-1266, 1175-1105 (SO2); UV (MeOH),
ꢁmax (log ꢂ): 279.4 (4.11), 205.0 (4.61); MS: m/e 376.1 (M+1)
(100%), 312.2 (9%), 258.2 (21%), 210.2 (8%), 119.0 (11%).
Anal Calcd. for C18H21N3O4S: C, 57.58; H, 5.64; N, 11.19; S,
8.54. Found: C, 57.69; H, 5.34; N, 11.27; S, 8.32.
Compound 10: Mp = 138-139 °C; 1H nmr (CDCl3): ꢀ 2.10 (m,
2H, CH2), 2.44 (s, 3H, OCH3), 3.36 (s, 3H, CH3), 3.55 (t, 2H,
OCH2, J = 5.9), 4.15 (t, 2H, OCH2, J = 6.2), 5.39 (s, 2H, CH2S),
6.82 (d, 1H, H-5, J = 7.3), 7.25 (m, 2H, aromat. H), 7.56 (bs,
2H, aromat. H), 8.20 (d, 1H, H-6, J = 7.3), 12.90 (bs, 1H, NH);
13C nmr (DMSO-d6, 120 °C): ꢀ 10.34, 28.41, 57.34, 60.62,
65.25, 68.13, 106.58, 116.38, 122.91, 123.76, 138.02, 147.09,
147.45, 148.16, 162.84; IR: 2990-2855, 1458 (CH3, CH2, CH),
3065, 1183, 1093 (Arom.), 1365-1265, 1175-1105 (SO2); UV
(MeOH), ꢁmax (log ꢂ): 278.2 (4.41), 206.2 (4.56); ms: m/e 392.3
(M+1) (32 %), 274.1 (100 %), 210.2 (43 %), 119.0 (68 %).
Anal Calcd. for C18H21N3O5S: C, 55.23; H, 5.41; N, 10.73; S,
8.19. Found: C, 54.98; H, 5.22; N, 11.06; S, 8.17.
Anal Calcd. for C18H21N3O3S: C, 60.15; H, 5.89; N, 11.69; S,
8.92. Found: C, 59.92; H, 6.12; N, 11.43; S, 8.62.
2-{[4-(3-Methoxypropoxy)-3-methyl-1-oxidopyridin-2-yl)methyl-
sulfinyl}-1H-benzoimidazole (11).
A solution of potassium hydrogencarbonate (0.4 g) in water (5
mL) was added to a solution of 13 (0.72 g, 2 mmol) in
dichloromethane (20 mL) and the mixture cooled to 0 °C in an
ice bath. To the cooled mixture was added a solution of 3-
chloroperbenzoic acid (1.8 mmol) in dichloromethane (10 mL)
over 2 h and the reaction mixture was stirred in an ice bath for
further 2 h. Then 10 ml of water were added and the aqueous
layer was separated. The organic layer was dried over
magnesium sulfate and evaporated. The residue (0.74 g) was
separated by column chromatography on silica gel,
dichloromethane – methanol – triethylamine, 90:5:2.5) to give
0.48 g of 11. This product was recrystallized from ethanol to
obtain 0.26 g of pure product 11 (35 %); m. p. 161-163 °C
(decomp.). 1H nmr (CDCl3): ꢀ 2.06 (m, 2H, CH2), 2.25 (s, 3H,
CH3), 3.34 (s, 3H, OCH3), 3.52 (t, 2H, CH2, J = 5.9), 4.11 (t, 2H,
CH2, J = 6.2), 6.77 (d, 1H, aromat. H, J = 7.3), 7.28-7.35 (m,
2H, aromat. H), 7.69 (br., 2H, pyridine H), 8.21 (d, 1H, aromat.
H, J = 7.3), 13.90 (bs, 1H, NH); ms, m/e: 375,13 (100,0%),
376,13 (19,9%), 377,12 (4,5%), 377,13 (3,1%), 376,12 (1,9%).
); IR: 3080-2850, 1617, 1566, 1429 (Arom.), 2935, 1458 (CH3,
CH2, CH), 1490-1430, 1100-1060, 835-690 (SO); UV (MeOH),
ꢁmax (log ꢂ): 279.2 (4.39), 206.8 (4.62); ms: m/e 376.4 (M+1)
(7%), 258.2 (100%), 244.1 (21 %), 194.3 (69 %), 164.3 (85%),
119.0 (78%).
2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine 1-oxide
(12).
The solution of 6b as the hydrochloride (4.93 g, 18.5 mmol)
in dichloromethane (150 mL) was washed with saturated
aqueous sodium hydrogencarbonate (200 mL). A solution of 3-
chloroperbenzoic acid (37 mmol) in a mixture of dichloro-
methane (20 mL) and methanol (6 mL) was added over 2 h to
the organic solution of 6b and the mixture stirred for 1 h.
Saturated aqueous sodium hydrogencarbonate (100 mL) was
added and the aqueous layer was extracted with dichloro-
methane (3 x 50 mL) and the combined organic layers were
dried with magnesium sulfate. Dichloromethane was then
evaporated under reduced pressure to obtain 12 (4.54 g, >99 %)
as oil, which was used for the next step without further
purification.
Anal Calcd. for C18H21N3O4S: C, 57.58; H, 5.64; N, 11.19; S,
8.54. Found: C, 57.77; H, 5.72; N, 11.35; S, 8.24.
2-{[4-(3-Methoxypropoxy)-3-methyl-1-oxidopyridin-2-yl]-
methyl}sulfonyl-1H-benzimidazole (10).
To a stirred solution of 13 (0.36 g, 1 mmol) in dichloro-
methane (10 mL) was added a solution of sodium carbonate (0.3
g) in water (3.0 mL) and the obtained mixture was cooled in an
ice bath. The solution of peracetic acid (0.3 g) in water (2 mL)
was added dropwise in 30 min and the mixture was stirred at
ambient temperature for 24 h. Then, 0.5 mL of peracetic acid
was added and the mixture was stirred at ambient temperature.
After 8 h 0.5 mL of peracetic acid was added and the mixture
was stirred for 20 h. When the presence of 11 was not indicated
on TLC, the reaction mixture was separated and the aqueous
layer was extracted with 10 mL of dichloromethane. The
2-{[4-(3-Methoxypropoxy)-3-methyl-1-oxidopyridin-2-yl]-
methylsulfanyl}-1H-benzoimidazole (13).
Triethylamine (9.49 g, 92.5 mmol) was added to a solution of 2-
chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine N-oxide
12 (4.54 g, 18.5 mmol) and 2-mercaptobenzoimidazole (2.78 g,