C. C. Aldrich et al.
MED
(ESIꢀ) calcd for C13H12NO4S2: [MꢀH]ꢀ 310.0213, found: 310.0207
afford a white amorphous solid (0.18 g, 94% yield): Rf =0.30
(hexane/EtOAc 4:1); mp: 200–2038C; 1H NMR (600 MHz,
[D6]DMSO): d=13.30 (brs, 1H), 7.98 (d, J=7.8 Hz, 1H), 7.28 (t, J=
7.8 Hz, 1H), 7.21 (t, J=7.8 Hz, 1H), 7.17 (d, J=8.4 Hz, 1H), 3.31 (s,
3H); 13C NMR (150 MHz, [D6]DMSO): d=172.8, 170.7, 131.8, 131.6,
126.1, 124.1, 116.1, 110.2, 28.7; IR: nmax =1725 cmꢀ1 (C=O); HRMS
(ESI+) calcd for C9H9N2OS: [M+H]+ 193.0430, found: 193.0423
(error 3.6 ppm).
(error 1.9 ppm).
3-(3,4-Dichlorophenylsulfonyl)-N-methylbenzenesulfonamide
(29). The title compound was prepared by following the general
procedure from 25 (0.38 g) to afford a white amorphous solid
(0.23 g 62%): Rf =0.40 (hexane/EtOAc 1.5:1); 1H NMR (600 MHz,
CDCl3): d=8.32 (s, 1H), 8.03 (d, J=7.8 Hz, 1H), 8.00 (d, J=7.8 Hz,
1H), 7.96 (d, J=2.4 Hz, 1H), 7.71 (dd, J=8.4, 2.4 Hz, 1H), 7.65 (t,
J=7.8 Hz, 1H), 7.55 (d, J=8.4 Hz, 1H), 2.52 (s, 3H); 13C NMR
(150 MHz, CDCl3): d=142.2, 141.5, 140.2, 139.2, 134.4, 132.2, 131.9,
131.4, 130.8, 129.8, 127.1, 126.4, 29.0; HRMS (ESIꢀ) calcd for
C13H10Cl2NO4S2: [MꢀH]ꢀ 377.9434, found: 377.9436 (error 0.5 ppm).
1-Acetyl-5/6-methylbenzimidazole-2-thione (41). The title com-
pound was prepared by following the general procedure from 36
(0.16 g) to afford a white amorphous solid (0.19 g, 93%) as an in-
separable 1:1 mixture of 5-methyl and 6-methyl regioisomers: Rf =
1
0.30 (hexane/EtOAc 4:1); H NMR (600 MHz, CD3OD + [D6]DMSO):
N-Benzyl-3-(3,4-dichlorophenylsulfonyl)benzenesulfonamide
(30). The title compound was prepared by following the general
procedure from 25 (0.38 g) to afford a white amorphous solid
(0.32 g, 60%): Rf =0.40 (hexane/EtOAc 1.5:1); 1H NMR (600 MHz,
CD3Cl3 + CD3OD): d=8.29 (s, 1H), 7.98 (d, J=7.8 Hz, 1H), 7.95 (d,
J=2.4 Hz, 1H), 7.93 (d, J=7.8 Hz, 1H), 7.69 (dd, J=8.4, 2.4 Hz, 1H),
7.56 (ovlp t, J=7.8 Hz, 1H), 7.55 (ovlp d, J=8.4 Hz, 1H), 7.16–7.13
(m, 3H), 7.07–7.05 (m, 2H), 4.08 (s, 2H); 13C NMR (150 MHz, CDCl3 +
CD3OD): d=143.0, 142.0, 140.3, 139.2, 136.0, 134.5, 132.0, 131.9,
131.2, 130.7, 129.8, 128.7, 128.1, 128.0, 127.1, 126.3, 47.2; HRMS
(ESIꢀ) calcd for C19H14Cl2NO4S2: [MꢀH]ꢀ 453.9747, found: 453.9756
(error 1.9 ppm).
d=7.94 (d, J=8.4 Hz, 1H), 7.92 (s, 1H), 7.10 (d, J=7.8 Hz, 1H), 7.02
(d, J=8.4 Hz, 2H), 6.96 (s, 1H), 3.04 (s, 3H), 3.02 (s, 3H), 2.39 (s,
3H), 2.38 (s, 3H); 13C NMR (150 MHz, CD3OD + [D6]DMSO): d=
172.3, 172.1, 170.9, 170.7, 135.4, 133.3, 131.2, 129.2, 125.8, 124.0,
115.8, 115.2, 109.6, 109.1, 109.0, 108.5, 27.4, 27.3, 20.5, 20.2; IR:
nmax =1688 cmꢀ1 (C=O); HRMS (ESI+) calcd for C10H11N2OS:
[M+H]+ 207.0587, found: 207.0579 (error 3.9 ppm).
1-Acetylbenzoxazole-2-thione (42). The title compound was pre-
pared by following the general procedure from 37 (0.15 g) to
afford a white amorphous solid (0.18 g, 94%): Rf =0.30 (hexane/
EtOAc 4:1); 1H NMR (600 MHz, CDCl3): d=8.06 (d, J=8.4 Hz, 1H),
7.33–7.29 (m, 3H), 3.05 (s, 3H); 13C NMR (150 MHz, CDCl3): d=
N-[3-(3,4-Dichlorophenylsulfonyl)phenylsulfonyl]morpholine
(31). The title compound was prepared by following the general
procedure from 25 (0.38 g) to afford a white amorphous solid
(0.30 g, 61%): Rf =0.40 (hexane/EtOAc 1.5:1); 1H NMR (600 MHz,
CDCl3): d=8.30 (s, 1H), 8.16 (d, J=7.8 Hz, 1H), 8.04 (d, J=1.8 Hz,
1H), 7.97 (d, J=7.8 Hz, 1H), 7.78 (ovlp dd, J=8.4, 1.8 Hz, 1H), 7.76
(ovlp t, J=7.8 Hz, 1H), 7.63 (d, J=8.4 Hz, 1H), 3.75 (t, J=4.8 Hz,
4H), 3.02 (t, J=4.8 Hz, 4H); 13C NMR (150 MHz, CDCl3): d=142.8,
140.4, 139.4, 137.8, 134.7, 132.6, 132.1, 132.0, 131.0, 130.0, 127.14,
127.11, 66.2, 46.1; HRMS (APCIꢀ) calcd for C16H13Cl2NO4S2:
[MꢀH2O]ꢀ 416.9669, found: 416.9670 (error 0.2 ppm).
179.4, 171.1, 146.7, 130.0, 126.4, 125.7, 116.7, 109.8, 27.9; IR: nmax =
1738 cmꢀ1 (C=O); HRMS (ESI+) calcd for C9H8NO2S: [M+H]+
194.0270, found: 194.0263 (error 3.6 ppm).
1-Acetyl-2-oxindole (43). The title compound was prepared by fol-
lowing the general procedure from 38 (0.13 g) to afford a white
amorphous solid (0.18 g, 96%): Rf =0.35 (hexane/EtOAc 4:1);
1H NMR (600 MHz, CDCl3): d=8.21 (d, J=8.4 Hz, 1H), 7.31 (t, J=
8.4 Hz, 1H), 7.26 (d, J=7.8 Hz, 1H), 7.18 (t, J=7.2 Hz, 1H), 3.71 (s,
2H), 2.67 (s, 3H); 13C NMR (150 MHz, CDCl3): d=175.3, 170.8, 141.4,
128.2, 124.9, 123.9, 123.4, 116.6, 36.6, 26.6; IR: nmax =1760,
1709 cmꢀ1 (C=O); HRMS (ESI+) calcd for C10H10NO2: [M+H]+
176.0706, found: 176.0710 (error 2.3 ppm).
N-[3-(3,4-Dichlorophenylsulfonyl)phenylsulfonyl]acetamide (32).
Ac2O (0.5 mL) was added to 3 followed by ZnCl2 (1.1 mg, 3 mol%).
The reaction mixture was heated at 508C for 30 min to afford a
clear solution. The reaction mixture was then cooled to room tem-
perature, concentrated in vacuo, and purified by silica gel chroma-
tography with 60% EtOAc/hexane to afford the title compound
(96 mg, 87%) as a white amorphous solid: Rf =0.30 (hexane/EtOAc
1-Acetylbenzimidazole (44). NaBH4 (2.27 g, 60.0 mmol) was added
portionwise (in 10 equal portions) to a solution of benzimidazole-
2-thione 34 (1.00 g, 6.65 mmol) and NiCl2 (2.6 g, 20.0 mmol) in
CH3OH (50 mL) over 60 min at 08C. Once the addition of the final
portion of NaBH4 was complete, the reaction was filtered, and the
filtrate was concentrated to afford a white solid, which was dis-
solved in EtOAc (50 mL), washed with H2O (40 mL), dried (MgSO4)
and concentrated to afford crude 35 (0.65 g, 83%).
1
1:1); H NMR (600 MHz, CD3OD): d=8.56 (s, 1H), 8.26 (ovlp d, J=
7.8 Hz, 1H), 8.24 (ovlp d, J=7.8 Hz, 1H), 8.15 (d, J=2.4 Hz, 1H),
7.90 (dd, J=8.4, 2.4 Hz, 1H), 7.82 (t, J=7.8 Hz, 1H), 7.77 (d, J=
8.4 Hz, 1H), 1.94 (s, 3H); 13C NMR (150 MHz, CD3OD): d=169.8,
142.0, 141.3, 141.0, 138.6, 133.9, 132.9, 132.5, 132.0, 130.8, 129.6,
127.6, 127.4, 22.1; HRMS (APCIꢀ) calcd for C14H10Cl2NO5S2: [MꢀH]ꢀ
405.9383, found: 405.9378 (error 1.2 ppm).
Crude 35 (0.2 g, 1.7 mmol) prepared above was acetylated using
the general procedure for acetylation and purified by flash chroma-
tography (hexane/EtOAc 4:1) to afford the title compound 44
(0.25 g, 93% yield) as a white amorphous solid: Rf =0.35 (hexane/
1
General procedure for the acetylation 4, 41–44, and 47. Ac2O
(6 mL) was added to compound 34–38, and 48 (1 mmol). The mix-
ture was heated at reflux for 3 h to provide a clear solution. The re-
action was cooled to room temperature, whereupon the product
precipitated. The resulting white solid was then filtered and
washed with cold CH2Cl2 to remove Ac2O to afford the product
(93–96% yield).
EtOAc 4:1); H NMR (600 MHz, CD3OD): d=8.69 (s, 1H), 8.16 (d, J=
8.4 Hz, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.37–7.35 (m, 2H), 2.72 (s, 3H);
13C NMR (150 MHz, CD3OD): d=168.6, 143.3, 143.2, 131.5, 125.7,
124.9, 119.4, 115.5, 22.5; IR: nmax =1726 cmꢀ1 (C=O); HRMS (ESI+)
calcd for C9H9N2O: [M+H]+ 161.0709, found: 161.0718 (error
5.5 ppm).
1-Acetylbenzimidazole-2-one (45). Benzimidazole-2-one (1.00 g,
7.5 mmol) 39 was acetylated by using the general procedure for
acetylation, which afforded the bis-acetylated adduct. Benzylamine
1-Acetylbenzimidazole-2-thione (5). The title compound was pre-
pared by following the general procedure from 34 (0.15 g) to
2086
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ChemMedChem 2010, 5, 2079 – 2087