F.Zaragoza / Tetrahedron 57 (2001) 5451±5454
5453
3.1. General procedure for the alkylation of thiols with
alcohols
7.17 #m, 2H), 7.49 #br s, 2H), 12.33 #br s, 1H). Anal.
calcd for C12H16N2S #220.34): C, 65.41; H, 7.32; N, 12.71.
Found: C, 64.78; H, 7.42; N, 13.00.
3.1.1. 5-Nitro-1H-benzimidazol-2-yl 2-pyridylmethyl
sul®de ꢀ4a). The phosphonium iodide 34,9 #299 mg,
1.23 mmol) was added to a mixture of 2-#hydroxymethyl)-
pyridine #146 mg, 1.34 mmol; 1a), 5-nitrobenzimidazole-2-
thiol #196 mg, 1.00 mmol; 2a), DIPEA #0.25 mL,
1.41 mmol), and propionitrile #3.0 mL), and the mixture
was stirred at 928C for 14 h. The mixture was allowed to
cool to room temperature, water #30 mL) was added, and the
product was extracted with dichloromethane #3£12 mL).
The combined organic layers were washed with brine
#20 mL), dried with magnesium sulfate, and concentrated
under reduced pressure. Recrystallization from acetonitrile
yielded 240 mg #84%) of the title compound as yellow
crystals: mp 194±1958C; HPLC-MS m/z 287 [MH1];
3.1.5. 1H-Benzimidazol-2-ylmethyl 4-chlorophenyl sul-
®de ꢀ4e). From 4-chloro-1-benzenethiol #244 mg, 1.69
mmol) and 2-#hydroxymethyl)benzimidazole #222 mg,
1.50 mmol) was obtained 278 mg #68%) of 4e as colorless
crystals: mp 187±1888C #MeCN); HPLC-MS m/z 275
[MH1]; nmax#KBr) 2912±2400 #br), 1474, 1438, 1404,
1273 cm21 1H NMR #300 MHz, DMSO-d6) d 4.45 #s,
;
2H), 7.12±7.17 #m, 2H), 7.33±7.38 #m, 2H), 7.41±7.55
#m, 4H), 12.44 #s, 1H). Anal. calcd for C14H11ClN2S
#274.77): C, 61.20; H, 4.04; N, 10.20. Found: C, 61.31; H,
4.09; N, 10.17.
3.1.6. 4-Nitrophenyl 2-ꢀN-phthalimidoyl)ethyl sul®de
ꢀ4f). From 4-nitro-1-benzenethiol #155 mg, 1.00 mmol)
and N-#2-hydroxyethyl)phthalimide #192 mg, 1.00 mmol)
was obtained 210 mg #64%) of 4f as yellow crystals: mp
180±1838C #MeCN); nmax#KBr) 1765, 1711, 1576, 1503,
n
max#KBr) 3085±2600 #br), 1621, 1591, 1570, 1510 cm21
;
1H NMR #300 MHz, DMSO-d6) d 4.76 #s, 2H), 7.29±7.35
#m, 1H), 7.56±7.67 #m, 2H), 7.75±7.82 #m, 1H), 8.08 #dd,
J8 Hz, 1 Hz, 1H), 8.34 #br s, 1H), 8.54±8.59 #m, 1H),
13.38 #br s, 1H). Anal. calcd for C13H10N4O2S #286.31):
C, 54.54; H, 3.52; N, 19.57. Found: C, 54.65; H, 3.51; N,
19.46.
1420 cm21 1H NMR #300 MHz, DMSO-d6) d 3.45 #t,
;
J7 Hz, 2H), 3.88 #t, J7 Hz, 2H), 7.56 #d, J9 Hz, 2H),
7.80±7.88 #m, 4H), 8.07 #d, J9 Hz, 2H). Anal. calcd for
C16H12N2O4S #328.35): C, 58.53; H, 3.68; N, 8.53. Found:
C, 58.85; H, 3.70; N, 8.58.
Using the same procedure as for 4a, the following thioethers
were prepared.
3.1.7. 2-ꢀN-Phthalimidoyl)ethyl 4-pyridyl sul®de ꢀ4g).
From 4-mercaptopyridine #110 mg, 0.99 mmol) and N-#2-
hydroxyethyl)phthalimide #192 mg, 1.00 mmol) was
obtained 152 mg #54%) of 4g as light-brown crystals: mp
3.1.2. 7/8-Nitro-3,4-dihydro-2H-benzo[4,5]imidazo[2,1-
b][1,3]thiazine ꢀ4b). From 5-nitrobenzimidazole-2-thiol
#274 mg, 1.40 mmol) and 1,3-propanediol #108 mg,
1.42 mmol) was obtained 233 mg #71%) of 4b as equimolar
mixture of two isomers. Yellow crystals, mp 204±2278C
#MeCN); HPLC-MS m/z 236 [MH1]; nmax #KBr) 1612,
148±1498C #MeCN); HPLC-MS m/z 285 [MH1];
1
n
max#KBr) 1765, 1706, 1576, 1396, 1356 cm21; H NMR
#300 MHz, DMSO-d6) d 3.37 #t, J7 Hz, 2H), 3.86 #t,
J7 Hz, 2H), 7.33 #m, 2H), 7.82±7.40 #m, 4H), 8.36 #m,
2H). Anal. calcd for C15H12N2O2S #284.34): C, 63.36; H,
4.25; N, 9.85. Found: C, 63.46; H, 4.31; N, 9.92.
1592, 1516, 1459, 1422 cm21
;
1H NMR #300 MHz,
DMSO-d6) d 2.31±2.41 #m, 2H), 3.35±3.40 #m, 2H),
4.29±4.39 #m, 2H), 7.60 #d, J9 Hz, 0.5H), 7.65 #d,
J9 Hz, 0.5H), 8.06±8.12 #m, 1H), 8.30 #br s, 0.5H), 8.43
#br s, 0.5H). Anal. calcd for C10H9N3O2S #235.27): C, 51.05;
H, 3.86; N, 17.86. Found: C, 51.12; H, 3.87; N, 17.75.
3.1.8. 4-Acetamidophenyl 4-nitrobenzyl sul®de ꢀ4h).
From 4-acetamido-1-benzenethiol #334 mg, 2.00 mmol)
and 4-nitrobenzylalcohol #309 mg, 2.02 mmol) was
obtained 461 mg #76%) of 4h as yellow crystals: mp 181±
1828C #MeCN); HPLC-MS m/z 303 [MH1]; nmax#KBr)
3.1.3. 1H-Benzimidazol-2-yl propyl sul®de ꢀ4c). From
2-mercaptobenzimidazole #152 mg, 1.01 mmol) and
1-propanol #66 mg, 1.11 mmol) was obtained 157 mg
#81%) of 4c as colorless crystals: mp 164±1658C
#MeCN); HPLC-MS m/z 193 [MH1]; nmax#KBr) 3054±
1
3308, 1662, 1586, 1516, 1347 cm21; H NMR #300 MHz,
DMSO-d6) d 2.02 #s, 3H), 4.28 #s, 2H), 7.27 #d, J9 Hz,
2H), 7.48±7.54 #m, 4H), 8.13 #d, J9 Hz, 2H), 9.97 #s, 1H).
Anal. calcd for C15H14N2O3S #302.35): C, 59.59; H, 4.67; N,
9.27. Found: C, 59.61; H, 4.73; N, 9.24.
;
2600 #br), 1505, 1432, 1395, 1346 cm21 1H NMR
#300 MHz, DMSO-d6) d 0.99 #t, J7 Hz, 3H), 1.73 #sext,
J7 Hz, 2H), 3.25 #t, J7 Hz, 2H), 7.08±7.14 #m, 2H),
7.32±7.39 #m, 1H), 7.47±7.53 #m, 1H), 12.49 #s, 1H).
Anal. calcd for C10H12N2S #192.28): C, 62.47; H, 6.29; N,
14.57. Found: C, 62.50; H, 6.27; N, 14.50.
Acknowledgements
I thank Vibeke Rode and Henriette Christensen for the
HPLC-MS analyses and Flemming Gundertofte for the
elemental analyses.
3.1.4. 1H-Benzimidazol-2-ylmethyl butyl sul®de ꢀ4d). An
excess of thiol #4 equiv.) was required to supress N-alkyl-
ation of the benzimidazole. From 1-butanethiol #0.86 mL,
8.01 mmol) and 2-#hydroxymethyl)benzimidazole #302 mg,
2.04 mmol) was obtained 170 mg #38%) of 4d as colorless
needles: mp 145±1468C #MeCN; Lit.10: 1448C); HPLC-MS
m/z 221 [MH1]; nmax#KBr) 2962±2533 #br), 1455, 1437,
References
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1275, 750 cm21; H NMR #300 MHz, DMSO-d6) d 0.83
È
2. #a) Zaragoza Dorwald, F. Organic Synthesis on Solid Phase;
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#t, J7 Hz, 3H), 1.32 #sext, J7 Hz, 2H), 1.49 #quint,
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