5802 J . Org. Chem., Vol. 65, No. 18, 2000
J eppesen et al.
(m, 8H), 1.54 (quintet, J ) 7.0 Hz, 4H), 2.37 (s, 3H), 2.82 (t, J
) 7.0 Hz, 4H), 7.33 (s, 2H), 7.41 (d, J ) 6.8 Hz, 2H), 7.79 (d,
J ) 6.8 Hz, 2H); 13C NMR (DMSO-d6) δ 13.7, 21.1, 21.6, 29.0,
30.00, 35.6, 112.5, 112.7, 117.2, 126.1, 126.8, 126.9, 130.3,
134.8, 145.7; MS (EI) m/z 601 (M+, 83), 446 (M+ - Ts, 100);
room temperature, followed by careful addition of brine (20
mL). The yellow suspension was extracted with CH2Cl2, after
which the yellow organic phase was washed with brine and
H2O. After drying (MgSO4) and evaporation of the solvent, the
resulting yellow oil was purified by column chromatography
(silica gel, CH2Cl2 or CH2Cl2/cyclohexane 1:4) to give pure
24a -c as yellow solids.
N-Meth yl-2-[4,5-bis(m eth ylth io)-1,3-dith iole-2-yliden e]-
(1,3)-d it h iolo[4,5-c]p yr r ole (24a ). Alkylation using iodo-
methane (0.06 mL, 0.14 g, 0.96 mmol): Rf ) 0.6 (CH2Cl2); yield
19.5 mg (93%); yellow orange solid; mp 101-102 °C (CH2Cl2);
1H NMR (DMSO-d6) δ 2.43 (s, 6H), 3.60 (s, 3H), 6.78 (s, 2H);
13C NMR (DMSO-d6) δ 18.4, 36.9, 107.2, 114.7, 116.8, 121.3,
126.2; MS (EI) m/z 349 (M+, 100), 334 (M+ - CH3, 21). Anal.
Calcd for C11H11NS6: C, 37.79; H, 3.17; N, 4.01. Found: C,
37.34; H, 3.28; N, 4.24
IR (KBr) ν 1372 (SO2), 1166 (SO2) cm-1. Anal. Calcd for C25H31
-
NO2S7: C, 49.88; H, 5.19; N, 2.33; S, 37.29. Found: C, 49.95;
H, 5.22; N, 2.38; S, 37.41.
2-[4,5-Bis(2-cya n oeth ylth io)-1,3-d ith iole-2-ylid en e]-N-
tosyl-(1,3)-d ith iolo[4,5-c]p yr r ole 22c. Compound 16b (3.00
g, 9.63 mmol) and 4,5-bis(2-cyanoethylthio)-1,3-dithiole-2-
thione (2.93 g, 9.63 mmol) were suspended in distilled P(OEt)3
(100 mL) and heated to 130 °C (during heating the two solids
dissolved leaving a red solution and after 10-15 min a yellow
orange precipitate was formed). Two additional portions of 4,5-
bis(2-cyanoethylthio)-1,3-dithiole-2-thione (a´ 1.47 g, 4.82 mmol)
were added after 10 and 20 min, respectively. The red reaction
mixture was stirred for 1 h at 130 °C, cooled to room
temperature and addition of MeOH (100 mL) yielded an orange
solid, which was filtered and washed with MeOH. The orange
powder was purified by column chromatography (silica gel,
CH2Cl2, Rf ) 0.2) to give 3.51 g (64%) of pure 22c as an orange
solid. Recrystallization from CH2Cl2/petroleum ether (bp 60-
80 °C) gave 22c as orange needles: mp 177-178 °C; 1H NMR
(DMSO-d6) δ 2.38 (s, 3H), 2.86 (t, J ) 6.6 Hz, 4H), 3.14 (t, J )
6.6 Hz, 4H), 7.39 (s, 2H), 7.46 (d, J ) 8.6 Hz, 2H), 7.82 (d, J
) 8.6 Hz, 2H); 13C NMR (DMSO-d6) δ 18.1, 21.0, 30.8, 112.0,
112.7, 118.1, 118.8, 125.9, 126.7, 127.2, 130.4, 134.4, 145.8;
MS (EI) m/z 567 (M+, 2); IR (KBr) ν 2251 (CN), 1375 (SO2),
1172 (SO2) cm-1. Anal. Calcd for C21H17N3O2S7: C, 44.42; H,
3.02; N, 7.40; S, 39.53. Found: C, 44.53; H, 2.98; N, 7.27; S,
39.63.
Gen er a l P r oced u r e for Detosyla tion of 22a a n d 22b.
A solution of 22a or 22b in anhyd THF-MeOH (1:1 v/v) was
degassed (N2, 15 min) before NaOMe (30% solution in MeOH,
15 equiv) was added in one portion. The yellow solution was
refluxed for 20 min, and after cooling to room temperature
purification was performed as described below.
2-[4,5-Bis(m eth ylth io)-1,3-dith iole-2-yliden e]-(1,3)-dith i-
olo[4,5-c]p yr r ole (23a ). 22a (0.37 g, 0.76 mmol) and THF-
MeOH (1:1 v/v, 50 mL). Removal of the solvent gave a yellow
residue, which was dissolved in CH2Cl2 (60 mL), washed with
H2O, and dried (MgSO4). Concentration in vacuo gave a yellow
orange solid, which was purified by column chromatography
(silica gel, CH2Cl2, Rf ) 0.3) to give 0.24 g (95%) of 23a as an
analytically pure yellow orange solid: mp 143.5-144 °C dec;
1H NMR (DMSO-d6) δ 2.44 (s, 6H), 6.81 (d, J ) 2.9 Hz, 2H),
11.14 (bs, 1H); 13C NMR (DMSO-d6) δ 18.4, 107.3, 110.9, 117.2,
122.0, 126.2; MS (EI) m/z 335 (M+, 100), 320 (M+ - CH3, 24).
Anal. Calcd for C10H9NS6: C, 35.80; H, 2.70; N, 4.17; S, 57.33.
Found: C, 35.91; H, 2.68; N, 4.15; S, 57.15.
2-[4,5-Bis(pen tylth io)-1,3-dith iole-2-yliden e]-(1,3)-dith i-
olo[4,5-c]p yr r ole (23b). 22b (2.69 g, 4.47 mmol) and THF-
MeOH (1:1 v/v, 100 mL). Removal of the solvent gave a yellow
residue, which was dissolved in CH2Cl2 (150 mL), washed with
H2O and brine, and dried (MgSO4). Concentration in vacuo
gave a yellow orange solid, which was purified by column
chromatography (silica gel, CH2Cl2, Rf ) 0.6) to give 1.77 g
(88%) of 23b as a dark oil, which upon standing solidifed giving
23b as analytically pure yellow crystals: mp 62-63 °C; 1H
NMR (DMSO-d6) δ 0.86 (t, J ) 7.0 Hz, 6H), 1.20-1.50 (m, 8H),
1.57 (quintet, J ) 7.0 Hz, 4H), 2.85 (t, J ) 7.0 Hz, 4H), 6.81
(d, J ) 2.3 Hz, 2H), 11.13 (bs, 1H); 13C NMR (DMSO-d6) δ
13.7, 21.5, 28.8, 29.8, 35.2, 107.3, 110.6, 117.0, 121.5, 126.6;
MS (EI) m/z 447 (M+, 100). Anal. Calcd for C18H25NS6: C,
48.28; H, 5.63; N, 3.13; S, 42.96. Found: C, 48.48; H, 5.57; N,
3.24; S, 42.84.
Gen er a l P r oced u r e for N-Alk yla tion of 23a . Compound
23a (20.2 mg, 0.060 mmol) was dissolved in anhyd DMF (3
mL) and degassed (N2, 15 min) before hexane washed sodium
hydride (10 mg, 0.42 mmol) was added in one portion. The
mixture was stirred for 15 min at room temperature, causing
the initially yellow solution to become orange, whereupon the
alkylating reagent was added in one portion, causing a color
change to yellow. The reaction mixture was stirred for 1 h at
N-Bu tyl-2-[4,5-bis(m eth ylth io)-1,3-d ith iole-2-ylid en e]-
(1,3)-d ith iolo[4,5-c]p yr r ole (24b). Meth od 1. Alkylation
using butyl bromide (0.10 mL of a 0.90 M solution in DMF,
0.090 mmol): Rf ) 0.8 (CH2Cl2); yield 21.0 mg (89%). Recrys-
tallization from CH2Cl2/petroleum ether (bp 60-80 °C) gave
24b as yellow plates suitable for X-ray analysis: mp 105.5-
106 °C; 1H NMR (CDCl3) δ 0.92 (t, J ) 7.3 Hz, 3H), 1.30 (sextet,
J ) 7.3 Hz, 2H), 1.70 (quintet, J ) 7.3 Hz, 2H), 2.42 (s, 6H),
3.81 (t, J ) 7.3 Hz, 2H), 6.45 (s, 2H); 13C NMR (CDCl3) δ 13.5,
19.1, 19.6, 33.4, 50.5, 110.2, 112.5, 118.5, 121.3, 127.3; MS (EI)
m/z 391 (M+, 100), 376 (M+ - CH3, 20). Anal. Calcd for C14H17
-
NS6: C, 42.93; H, 4.37; N, 3.58; S, 49.11. Found: C, 43.03; H,
4.34; N, 3.69; S, 48.99.
N-Ben zyl-2-[4,5-bis(m eth ylth io)-1,3-dith iole-2-ylid en e]-
(1,3)-d ith iolo[4,5-c]p yr r ole (24c). Like 24a ,b, except that
the reaction was performed on a larger scale. Compound 23a
(70.0 mg, 0.21 mmol), DMF (10 mL) and NaH (50 mg, 2.1
mmol). Alkylation using benzyl bromide (0.25 mL, 0.36 g, 2.10
mmol): Rf ) 0.25 (CH2Cl2/cyclohexane 1:4); yield 80.0 mg
(90%). Recrystallization from CH2Cl2/petroleum ether (bp 60-
80 °C) gave 24c as yellow needles: mp 133-134 °C; 1H NMR
(DMSO-d6) δ 2.43 (s, 6H), 5.07 (s, 2H), 6.88 (s, 2H), 7.27 (m,
5H); 13C NMR (DMSO-d6) δ 18.4, 53.3, 107.7, 113.9, 117.3,
121.0, 126.0, 127.2, 127.6, 128.6, 138.2; MS (EI) m/z 425 (M+,
76), 410 (M+ - CH3, 11). Anal. Calcd for C17H15NS6: C, 47.97;
H, 3.55; N, 3.29; S, 45.19. Found: C, 48.09; H, 3.52; N, 3.21;
S, 45.23.
P oten tia l of 22c a s a Bu ild in g Block for Su p r a m olecu -
la r Ch em istr y. 2-[4-(2-Cya n oeth ylth io)-5-m eth ylth io-1,3-
dith iole-2-yliden e]-N-tosyl-(1,3)-dith iolo[4,5-c]pyr r ole (25).
A solution of 22c (0.100 g, 0.18 mmol) in anhyd THF (10 mL)
was degassed (N2, 15 min) before a solution of CsOH‚H2O
(0.032 g, 0.19 mmol) in anhyd MeOH (1 mL) was added
dropwise via a syringe over a period of 1 h. The mixture was
stirred for 15 min, whereupon MeI (0.52 mL, excess) was added
in one portion. After stirring for further 30 min and removal
of the solvent, the yellow residue was purified by column
chromatography (silica gel, CH2Cl2/cyclohexane 2:1, Rf ) 0.35)
to give 0.089 g (96%) of 25 as an analytically pure yellow
solid: mp 186.5-187 °C (CH2Cl2/cyclohexane); 1H NMR (DMSO-
d6) δ 2.39 (s, 3H), 2.47 (s, 3H), 2.83 (t, J ) 6.6 Hz, 2H), 3.10 (t,
J ) 6.6 Hz, 2H), 7.39 (s, 2H), 7.46 (d, J ) 8.2 Hz, 2H), 7.82 (d,
J ) 8.2 Hz, 2H); 13C NMR (DMSO-d6) δ 18.0, 18.4, 21.0, 30.7,
112.2, 112.6, 117.6, 118.7, 120.6, 125.8, 125.8, 126.7, 130.3,
132.5, 134.3, 145.7 two lines overlapping; MS (EI) m/z 528 (M+,
40), 373 (M+ - Ts, 71); IR (KBr) ν 2251 (CN), 1372 (SO2), 1172
(SO2) cm-1. Anal. Calcd for C19H16N2O2S7: C, 43.16; H, 3.05;
N, 5.29; S, 42.45. Found: C, 43.21; H, 3.03; N, 5.20; S, 42.54.
2-[4,5-Bis(m eth ylth io)-1,3-d ith iole-2-ylid en e]-N-tosyl-
(1,3)-d ith iolo[4,5-c]p yr r ole 22a . Meth od 2. A solution of 25
(0.050 g, 0.095 mmol) in anhyd THF (10 mL) was degassed
(N2, 15 min) before a solution of CsOH‚H2O (0.017 g, 0.10
mmol) in anhyd MeOH (1 mL) was added dropwise via a
syringe over a period of 1 h. The mixture was stirred for 15
min, whereupon MeI (0.10 mL, excess) was added in one
portion. After stirring for further 30 min and removal of the
solvent the yellow residue was purified by column chroma-
tography (silica gel, CH2Cl2/cyclohexane 1:1, Rf ) 0.3) to give