Notes
J . Org. Chem., Vol. 64, No. 17, 1999 6485
(CDCl3, 75 MHz) δ 12.79, 45.28, 55.77, 111.97, 114.99, 116.04,
118.78, 124.63, 127.05, 128.53, 129.39, 130.72, 133.30, 135.50,
136.53, 136.63, 142.16, 149.54, 161.36; IR (neat) 3048, 2968,
1589, 1489, 1434, 1347, 1251, 1171 cm-1; MS m/z 395 (M+, 55.0),
380 (100). Anal. Calcd for C23H25NOS2: C, 69.83; H, 6.37; N,
3.54; S, 16.21. Found: C, 69.78; H, 6.35; N, 3.40; S, 16.05. 5a :
oily liquid; 1H NMR (CDCl3, 300 MHz) δ 1.00 (t, J ) 7.09 Hz,
6H), 3.05 (q, J ) 7.06 Hz, 4H), 3.75 (s, 3H), 6.63 (d, J ) 8.06
Hz, 1H), 6.72 (d, J ) 7.75 Hz, 1H), 6.83-6.89 (m, 3H), 6.98-
7.10 (m, 4H), 7.35 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ 12.54,
47.80, 55.35, 115.16, 122.98, 123.27, 124.49, 125.58 (two car-
bons), 127.14 (two carbons), 128.92, 130.55, 135.94, 136.18,
136.76, 145.71, 148.21, 160.25; IR (neat) 3051, 2969, 2930, 2833,
1585, 1491, 1441, 1368, 1247, 1174, 1031 cm-1; MS m/z 395 (M+,
100), 380 (41.7). Anal. Calcd for C23H25NOS2: C, 69.83; H, 6.37;
N, 3.54; S, 16.21. Found: C, 69.74; H, 6.36; N, 3.42; S, 16.30.
Rea ction of 1a w ith LDA in th e P r esen ce of 2,5-Dim eth -
ylfu r a n . LDA (0.6 mmol, 2 M in n-hexane) was dropwise added
into a suspension of 1a (209 mg, 0.49 mmol) in 2,5-dimethylfuran
at reflux under nitrogen atmosphere. After the addition of the
same amount of LDA was repeated four times as described in
the general procedure, chromatography of the reaction mixture
using a mixture of EtOAc and n-hexane (1:9) gave 2-(4-ani-
sylthio)-3′-(N,N-diisopropylamino)diphenyl sulfide (4c) (26 mg,
12%) [oily liquid; 1H NMR (CDCl3, 300 MHz) δ 1.15 (s, 6H), 1.17
(s, 6H), 3.74 (hept, J ) 6.76 Hz, 2H), 3.82 (s, 3H), 6.73-6.77 (m,
3H), 6.84-6.88 (m, 1H), 6.91 (d, J ) 8.71 Hz, 2H), 7.03-7.07
(m, 2H), 7.13 (t, J ) 8.12 Hz, 1H), 7.23-7.26 (m, 1H), 7.42 (d, J
) 8.69 Hz, 2H); 13C NMR (CDCl3, 75 MHz) δ 21.65, 47.89, 55.78,
115.57, 117.07, 120.19, 120.49, 123.90, 126.45, 128.08, 128.48,
129.63, 132.91, 134.39, 135.06, 136.43, 141.82, 149.28, 160.48;
IR (neat) 3050, 2968, 2930, 2830, 1580, 1490,1444, 1370, 1249,
1170,1032 cm-1; MS m/z 423 (M+, 28.3), 408 (100). Anal. Calcd
for C25H29NOS2: C, 70.80; H, 6.90; N, 3.31; S, 15.14. Found: C,
70.80; H, 6.88; N, 3.25; S, 15.00] and 1,4-dimethyl-5-[2-(4-
anisylthio)phenylthio]-1,4-dihydronaphthalene (6) (47 mg,
23%): oily liquid; 1H NMR (CDCl3, 300 MHz) 1.81 (s, 3H), 1.90
(s, 3H), 6.23-6.72 (m, 3H), 6.78-6.87 (m, 4H), 6.88-6.95 (m,
3H), 7.00 (d, J ) 6.81 Hz, 1H), 7.31 (d, J ) 8.70 Hz, 2H); 13C
NMR (CDCl3, 75 MHz), 15.20, 17.16, 55.36, 88.10, 90.69, 115.09,
118.11, 123.88, 125.48, 126.29, 126.65, 126.75, 129.65, 129.79,
130.90, 135.15, 137.01, 137.61, 146.76, 146.83, 154.52, 154.68,
159.89; IR (neat) 3055, 2975, 2932, 1591, 1492, 1442, 1247, 1032
cm-1; MS m/z 418 (M+, 46.7), 402 (11.3), 235 (100), 221 (67.5).
Anal. Calcd for C25H22O2S2: C, 71.74; H, 5.30; S, 15.32. Found:
C, 71.68; H, 5.36; S, 15.37. Elution with a mixture of MeOH and
CHCl3 (1:9) gave unreacted 1a (62 mg, 30%).
Rea ction w ith 1,4,10,13-Tetr a oxa -7,16-d ia za cycloocta -
d eca n e. A mixture of 1a (970 mg, 2.29 mmol), the foregoing
diazacyclooctadecane (100 mg, 0.38 mmol), and LDA in THF was
heated for 4 h at reflux. Chromatography of the reaction mixture
using a mixture of EtOAc and n-hexane (1:3) gave 3 (7 mg, 8%)
and 2-(4-anisylthio)-3′-(N,N-diisopropylamino)diphenyl sulfide
(4c) (58 mg, 36%). Subsequent elution with EtOAc gave N,N-
di[3-[2-(4-anisylthio)phenylthio]]phenyl-1,4,10,13-tetraoxa-7,16-
diazacyclooctadecane (4b) (190 mg, 55%): mp 141-144 °C
(EtOH); 1H NMR (CDCl3, 300 MHz) δ 3.50-3.64 (m, 24H), 3.82
(s, 6H), 6.56 (d, J ) 8.49 Hz, 2H), 6.63 (overlap of singlet and
doublet, 4H), 6.85-6.88 (m, 2H), 6.91 (d, J ) 8.72 Hz, 2H), 6.99-
7.08 (m, 4H), 7.14 (t, J ) 7.93 Hz, 2H), 7.20-7.23 (m, 2H), 7.42
(d, J ) 8.93 Hz, 4H); 13C NMR (CDCl3, 75 MHz) δ 51.22, 55.36,
68.95, 70.91, 110.53, 113.71, 115.15, 118.39, 123.49, 126.09,
127.60, 128.23, 130.00, 132.20, 134.15, 135.58, 135.92, 141.09,
148.59, 160.06; IR (neat) 2856, 1579, 1480, 1434, 1246, 1099,
1026 cm-1. FAB MS m/z 907 (M+, 10.8), 154 (100). Anal. Calcd
for C50H54N2O6S4: C, 66.19; H, 6.00; N, 3.09; S, 14.14. Found:
C, 66.05; H, 5.97; N, 2.99; S, 14.21.
2-bromo-1,4-dimethoxy-3-methylthiobenzene (8), which was sepa-
rated by elution with the same solvent mixture (1:40) to give 7
(309 mg, 73%): oily liquid; 1H NMR (CDCl3, 300 MHz) δ 2.33
(s, 3H), 3.85 (s, 3H), 6.76 (s, 1H), 6.90 (d, J ) 9.00 Hz, 1H), 6.95
(d, J ) 9.02 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ 18.69, 57.55,
113.84, 115.66, 120.16, 123.10, 150.90, 152.27; IR (neat) 3376,
3064, 2912, 1560, 1462, 1426, 1315, 1266, 1195, 1174, 1088,
1045, 973, 906, 802, 715, 587, 542 cm-1; MS m/z 248 (M+, 100%),
250 (M+ + 2, 100), 233 (58.2) and 8 (14 mg, 3%): oily liquid; 1H
NMR (CDCl3, 300 MHz) δ 2.44 (s, 3H), 3.87 (s, 3H), 3.89 (s, 3H),
6.84 (d, J ) 9.05 Hz, 1H), 6.88 (d, J ) 9.03 Hz, 1H); IR (neat)
2912, 1568, 1466, 1432, 1371, 1290, 1136, 1078, 1046, 1018, 952,
819, 805, 747 cm-1; MS m/z 262 (M+, 90.5) 264 (M+ + 2, 90.8),
249 (30.3), 168 (100).
3-Br om o-4-m eth oxy-2-(m eth ylth io)p h en yl Aceta te (9). To
a solution of 7 (113 mg, 0.454 mmol) and acetyl chloride (39 mg,
0.499 mmol) in CH2Cl2 (30 mL) was added triethylamine (51
mg, 0.499 mmol). The mixture was stirred for 30 min at room
temperature, followed by addition of water (2 mL). After removal
of the solvent, the residue was extracted with CH2Cl2 (2 × 30
mL) and dried over MgSO4. Evaluation of the solvent gave 9
(124 mg, 94%), which was recrystallized from a mixture of
n-hexane and CH2Cl2: mp 89-91 °C; 1H NMR (CDCl3, 300 MHz)
δ 2.33 (s, 3H), 2.37 (s, 3H), 3.90 (s, 3H), 6.89 (d, J ) 8.91 Hz,
1H), 7.04 (d, J ) 8.91 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ
18.36, 20.87, 56.73, 112.07, 120.79, 121.58, 132.40, 146.47,
154.82, 169.81; IR (KBr) 3064, 2920, 2824,1762, 1556, 1456,
1432, 1360, 1302, 1275, 1258, 1202, 1086, 1038, 1010, 973, 938,
922, 878 cm-1; MS m/z 290 (M+, 8.5), 292 (M+ + 2, 8.8), 250
(100). Anal. Calcd for C10H11BrO3S: C, 41.25; H, 3.81; S, 11.01.
Found: C, 41.28; H, 3.95; S, 11.39.
Gen er a l P r oced u r e for th e Rea ction s of 5-[3-Ha lo-4-
(m eth oxy)p h en yl]th ia n th r en iu m yl P er ch lor a tes (1b -e)
w ith P ota ssiu m ter t-Bu toxid e in th e P r esen ce of 2,5-
Dim eth ylfu r a n . To a mixture of 2,5-dimethylfuran and t-BuOK
in dried THF (20 mL) at reflux under nitrogen atmosphere was
dropwise added a suspension of 1b-e in THF (10 mL), prepared
by using a sonicator, for 2.5 h. The mixture was heated for 30
min at reflux. After removal of the solvent in vacuo, the residue
was chromatographed (3 × 10 cm). Elution with n-hexane gave
3. Elution with a mixture of EtOAc and n-hexane (1:9) gave 1,4-
dimethyl-1,4-epoxy-5-halo-6-methoxy-1,4-dihydronaphtha-
lenes (12a -d ). Elution with acetone gave a mixture of unreacted
1b-e and unknown mixtures.
(i) Rea ction w ith 1b. A mixture of 1b (200 mg, 0.40 mmol),
t-BuOK (120 mg, 1.07 mmol), and 2,5-dimethylfuran (1,920 mg,
20.0 mmol) in THF was heated for 3 h at reflux. From the
reaction mixture were obtained 3 (82 mg, 95%), 5-bromo-1,4-
dimethyl-1,4-epoxy-6-methoxy-1,4-dihydronaphthalene (12a ) (85
mg, 75%), and a mixture of unreacted 1b and an unknown (14
mg). Compound 12a was recrystallized from a mixture of EtOAc
and n-hexane to give white crystals: mp 126-128 °C; 1H NMR
(CDCl3, 300 MHz) δ 1.78 (s, 3H), 1.99 (s, 3H), 3.75 (s, 3H), 6.31
(d, J ) 7.67 Hz, 1H) 6.68 (d, J ) 5.33 Hz, 1H), 6.74 (d, J ) 5.32
Hz, 1H), 6.83 (d, J ) 7.64 Hz, 1H); 13C NMR (CDCl3, 75 MHz)
δ 15.17, 17.70, 56.68, 88.00, 91.22, 106.21, 106.58, 116.89, 145.87,
146.76, 147.40, 152.73, 153.55; IR (KBr) 2928, 1450, 1420, 1376,
1334, 1293, 1251, 1126, 1043 cm-1; MS m/z 280 (M+, 26.3), 282
(M+ + 2, 25.6), 254 (61.0), 239 (100). Anal. Calcd for C13H13
BrO2: C, 55.54; H, 4.66. Found: C, 55.52; H, 5.30.
-
(ii) Rea ction w ith 5-[3-F lu or o-4-(m eth oxy)p h en yl]th i-
a n th r en iu m yl P er ch lor a te (1c). A mixture of 1c (176 mg, 0.40
mmol), t-BuOK (135 mg, 1.20 mmol), and 2,5-dimethylfuran (961
mg, 10.0 mmol) in THF was heated for 4 h at reflux. From the
reaction mixture were obtained 3 (83 mg, 96%), 1,4-dimethyl-
1,4-epoxy-5-fluoro-6-methoxy-1,4-dihydronaphthalene (12b) (78
mg, 88%), and unreacted 1c (4 mg, 2%). 12b: oily liquid; 1H
NMR (CDCl3, 300 MHz) δ 1.78 (s, 3H), 1.95 (d, J ) 10 Hz, 3H),
3.74 (s, 3H), 6.38 (t, J ) 7.36 Hz, 1H), 6.73-6.67 (m, 3H); 13C
NMR (CDCl3, 75 MHz) δ 15.19, 16.65, 56.55, 88.67 (d, J ) 1.60
Hz), 88.75, 108.30, 113.41 (d, J ) 3.45 Hz), 137.38 (d, J ) 15.3
Hz), 145.95, 146.59 (d, J ) 12.0 Hz), 146.73 (d, J ) 249 Hz),
146.92 (d, J ) 2.80 Hz), 147.06; IR (neat) 2977, 2936, 1490, 1440,
1384, 1360, 1303, 1264, 1237, 1149, 1080, 1049, 858, 807, 729
cm-1; MS m/z 220 (M+, 43.5), 205 (12.1), 194 (64.3), 177 (100).
Rea ction of 5-(3-Br om o-4-m eth oxyp h en yl)th ia n th r en i-
u m yl P er ch lor a te (1b) w ith P ota ssiu m ter t-Bu toxid e. To
a solution of 1b (989 mg, 1.69 mmol) in DMSO (30 mL) was
added t-BuOK (417 mg, 3.71 mmol). The mixture was stirred
for 1.5 h at room temperature, followed by addition of water (30
mL). The mixture was extracted with EtOAc (9 × 30 mL) and
worked up as usual. Chromatography (1.5 × 10 cm) of the
reaction mixture using n-hexane gave 3 (323 mg, 88%). Subse-
quent elution with a mixture of EtOAc and n-hexane (1:9) gave
a mixture of 3-bromo-4-methoxy-2-(methylthio)phenol (7) and