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N. Le Fur et al. / Tetrahedron 60 (2004) 7983–7994
performed according to the general procedure for prepa-
ration of sulfides with thiophenol (0.4 ml, 3.65 mmol) in
15 ml of THF, n-butyllithium 1.6 M (2.3 ml, 3.65 mmol)
and 4-chlorocinnoline 1 (0.5 g, 3.04 mmol) dissolved in
10 ml of THF. u¼66 8C, t¼2 h 30 min. A purification by
column chromatography on silica gel with dichloromethane/
ethyl acetate (8/2) as eluent gave 2b (0.67 g, 93%) as a
yellow solid. Mp¼135 8C. 1H NMR (CDCl3): d¼8.54
(s, 1H, H3); 8.40 (d, J8–7¼9.0 Hz, 1H, H8); 8.06 (d,
J5–6¼7.9 Hz, 1H, H5); 7.74 (m, 2H, H6þH7); 7.55 (m, 2H,
SPh); 7.44 (m, 3H, SPh). 13C NMR (CDCl3): d¼147.5 (C);
140.6 (CH); 137.7 (C); 134.3 (CH); 129.9 (CH); 129.7
(CH); 129.3 (CH); 129.2 (CH); 129.0 (CH); 126.5 (C);
122.8 (C); 121.6 (CH). IR (KBr) (cm21): 3058, 1614,
1555, 1480, 1396, 1225, 754, 672, 552. Anal. calcd for
C14H10N2S: C, 70.56; H, 4.23; N, 11.75; S, 13.46. Found: C,
70.38; H, 4.28; N, 11.67; S, 13.39%.
(C). IR (KBr) (cm21): 3056, 1610, 1556, 1439, 1403, 1145,
1051, 767, 746, 685. Anal. calcd for C14H10N2OS: C, 66.12;
H, 3.96; N, 11.02; S, 12.61. Found: C, 66.22; H, 4.15; N,
10.91; S, 12.35%.
4.3.6. 4-tert-Butylsulfonylcinnoline (4). 4-tert-Butylsulfa-
nylcinnoline 2a (0.3 g, 1.37 mmol) in acetic acid (20 ml,
8 N) was stirred at room temperature while KMnO4 (0.8 g,
5.06 mmol) in water (30 ml) was added during 30 min. the
reaction mixture was chilled to 15 8C and decolourised by
an aqueous solution of Na2SO3 (5%). 4-tert-butylsulfonyl-
cinnoline 4 was collected to give (0.2 g, 59%) as a yellow
solid. Mp¼140 8C. 1H NMR (CDCl3): d¼9.59 (s, 1H); 8.82
(m, 1H); 8.64 (m, 1H); 7.91 (m, 2H); 1.34 (s, 9H). 13C NMR
(CDCl3): d¼(152.2 (C); 145.8 (CH); 134.3 (CH); 131.9
(CH); 131.4 (CH); 128.4 (C); 125.0 (CH); 123.0 (C); 62.8
(C); 23.9 (CH3). IR (KBr) (cm21): 2939–3091, 1483, 1374,
1306, 1147, 1116, 763, 693, 580, 489. Anal. calcd for
C12H14N2O2S: C, 57.53; H, 5.59; N, 11.19; S, 12.82. Found:
C, 57.42; H, 5.28; N, 11.17; S, 12.58%.
4.3.3. 4-Methylsulfanylcinnoline (2c). Synthesis of 2c was
performed according to the general procedure for prepa-
ration of sulfides with methyl disulfide (0.65 ml,
7.32 mmol) in 10 ml of THF, n-butyllithium 1.6 M
4.3.7. 6,7-Dimethoxy-4-tert-butylsulfinylcinnoline (6a).
Oxidation of a solution of 6,7-dimethoxy-4-tert-butylsulfa-
nylcinnoline 13a (1.02 g, 3.59 mmol) in dichloromethane
(60 ml), was performed according to the general procedure
with m-CPBA (2£0.44 g, 2£1.8 mmol) dissolved in dichloro-
methane (2£5 ml), giving after purification by column
chromatography on silica gel with ethyl acetate as eluent, 6a
(0.876 g, 83%) as yellow solid. Mp¼172 8C. 1H NMR
(CDCl3): d¼9.38 (s, 1H); 8.09 (s, 1H); 7.79 (s, 1H); 4.07 (s,
3H); 4.04 (s, 3H); 1.34 (s, 9H). 13C NMR (CDCl3): d¼156.2
(C); 154.1 (C); 145.1 (CH); 126.1 (C); 121.5 (C); 107.9
(CH); 101.4 (CH); 63.0 (C); 57.2 (CH3); 57.0 (CH3); 23.9
(CH3). IR (KBr) (cm21): 2990–3120, 1495, 1298, 1117,
576. Anal. calcd for C14H18N2O3S: C, 57.12; H, 6.16; N,
9.52. Found: C, 56.65; H, 6.06; N, 9.27%.
(4.58 ml, 7.32 mmol) and 4-chlorocinnoline
1 (1 g,
6.1 mmol) dissolved in 10 ml of THF. u¼66 8C, t¼1 h
10 min. A purification by column chromatography on silica
gel with dichloromethane/ethyl acetate (1/1) as eluent gave
2c (0.79 g, 74%) as a yellow solid. Mp¼96 8C (lit.38¼
1
98 8C). H NMR (CDCl3): d¼9.01 (s, 1H, H3); 8.40 (d,
J8–7¼8.5 Hz, 1H, H8); 7.91 (d, J5–6¼8.2 Hz, 1H, H5); 7.72
(m, 2H, H6þH7); 2.63 (s, 3H, CH3).
4.3.4. 4-tert-Butylsulfinylcinnoline (3a). Oxidation of a
solution of 4-tert-butylsulfanylcinnoline 2a (3.27 g,
15 mmol), in dichloromethane (250 ml), was performed
according to the general procedure with m-CPBA
(2£1.85 g, 2£7.5 mmol) dissolved in dichloromethane
(2£60 ml), giving after purification by column chroma-
tography on silica gel with ethyl acetate as eluent, 3a
4.3.8. 6,7-Dimethoxy-4-p-tolylsulfinylcinnoline (6b). Oxi-
dation of a solution of 6,7-dimethoxy-4-p-tolylsulfanyl-
cinnoline 13b (0.15 g, 0.48 mmol) in dichloromethane
(20 ml), was performed according to the general procedure
with m-CPBA (2£0.06 g, 2£0.24 mmol) dissolved in
dichloromethane (2£2 ml), giving after purification by
column chromatography on silica gel with a mixture of
dichloromethane/acetone (4/1) as eluent, 6b (0.06 g, 37%)
as yellow solid. Mp¼242 8C. 1H NMR (CDCl3): d¼9.42 (s,
1H); 7.71 (s, 1H); 7.53 (d, J¼8.3 Hz, 2H); 7.26 (s, 1H); 7.20
(d, J¼7.9 Hz, 2H); 4.00 (s, 3H); 3.93 (s, 3H); 2.29 (s, 3H).
13C NMR (CDCl3): d¼155.0 (C); 153.9 (C); 149.2 (C);
143.3 (C); 140.0 (C); 139.4 (CH); 137.1 (C); 130.8 (CH);
125.9 (CH); 119.6 (C); 108.0 (CH); 98.8 (CH); 57.0 (CH3);
56.9 (CH3); 21.8 (CH3). IR (KBr) (cm21): 2854–3079,
14,989, 1428, 1297, 1258, 1216, 1055, 1011, 819, 510.
Anal. calcd for C17H16N2O3S: C, 62.18; H, 4.91; N, 8.53.
Found: C, 61.92; H, 4.53; N, 8.35%.
1
(3.12 g, 89%) as a orange solid. Mp¼117 8C. H NMR
(CDCl3): d¼9.57 (s, 1H, H3); 8.59 (d, J7–8¼8.5 Hz, 1H,
H8); 8.14 (d, J5–6¼8.0 Hz, 1H, H5,); 7.85 (m, 2H, H6þH7);
1.23 (s, 9H, (CH3)3). 13C NMR (CDCl3): d¼150.1 (C9);
142.1 (C3); 136.2 (C4); 132.7 (C6); 131.6 (C7); 131.0 (C8);
124.4 (C10); 123.2 (C5); 59.7 (C, tBu); 23.7 (CH3, tBu). IR
(KBr) (cm21): 2868–3100, 1611, 1552, 1483, 1397, 1366,
1167, 1048, 784, 670. Anal. calcd for C12H14N2OS: C,
61.45; H, 5.97; N, 11.95; S, 13.70. Found: C, 61.22; H, 5.98;
N, 11.92; S, 13.56%.
4.3.5. 4-Phenylsulfinylcinnoline (3b). Oxidation of a
solution of 4-phenylsulfanylcinnoline 2b (0.20 g,
0.84 mmol), in dichloromethane (20 ml), was performed
according to the general procedure with m-CPBA
(2£0.11 g, 2£0.42 mmol) dissolved in dichloromethane
(2£5 ml), giving after purification by column chroma-
tography on silica gel with a mixture of ethyl acetate/ether
petroleum (1/1) as eluent, 3b (94 mg, 44%) as a yellow
4.3.9. 4-Chloro-3-tert-butylcinnoline (6) and 3-tert-butyl-
cinnolin-4-ol (7). A suspension of 2-(3,3-dimethyl-1-
butynyl)-phenylamine (0.5 g, 2.89 mmol) in 5 ml of water
was stirred and cooled to 0 8C. 5 ml of a 36% aqueous
solution of aqueous hydrochloric acid was added then,
dropwise, a solution of NaNO2 (0.31 g, 4.49 mmol)
dissolved in 1 ml of water. The reaction mixture was
1
solid. Mp¼157 8C. H NMR (CDCl3): d¼9.72 (s, 1H, H3);
8.56 (d, J7–8¼8.42 Hz, 1H, H8); 8.10 (d, J5–6¼7.54 Hz, 1H,
H5); 7.76 (m, 4H, H6þH7 and 2H of SOPh); 7.39 (m, 3H,
SOPh). 13C NMR (CDCl3): d¼150.5 (C); 143.3 (C); 140.0
(C); 139.6 (CH); 133.1 (CH); 132.6 (CH); 131.7 (CH);
131.4 (CH); 130.3 (CH); 125.9 (CH); 122.1 (CH); 121.8