3,4-Alkylenedioxypyrroles
J . Org. Chem., Vol. 66, No. 21, 2001 6881
raphy on silica gel using hexane/ethyl acetate (2:1) as eluent
afforded diol 37b as a clear oil (4.8 g, 70%): 1H NMR (300
MHz, CDCl3) 3.80 (dd, J ) 10.4, 3.8 Hz, 2H), 3.61 (dd, J )
10.4, 8.2 Hz, 2H), 2.65 (s, 2H), 1.84 (m, 1H), 1.38-1.20 (m,
9H), 1.20-1.08 (m, 2H), 0.90 (t, J ) 6.6 Hz, 3H), 0.83 (t, J )
7.7 Hz, 3H).
0.5 h at 90 °C. After cooling to room temperature, the
trifluroacetic acid was removed by rotary evaporator, and the
residue was neutralized by aqueous saturated sodium bicar-
bonate. The aqueous phase was extracted with ether (3 × 100
mL), and the combined ether layers were dried over MgSO4.
Purification by chromatography on silica gel using hexane/
ethyl acetate (3:1) as eluent afforded the product.
2-Octyl-1,3-p r op a n ed iol (37a ). A colorless crystal (5.2 g,
1
75%) (lit.31); mp 45-46 °C; H NMR (300 MHz, CDCl3) 3.83
Dieth yl 3,4-(2-Octyl-1,3-p r op ylen ed ioxy)p yr r ole-2,5-d i-
1
(dd, J ) 10.4, 3.3 Hz, 2H), 3.66 (dd, J ) 11.0, 7.7 Hz, 2H),
2.42 (s, 2H), 1.78 (m, 1H), 1.40-1.20 (m, 14H), 0.88 (t, J ) 6.6
Hz, 3H).
ca r boxyla te (41a ). A pale yellow oil (2.80 g, 72%); H NMR
(300 MHz, CDCl3) 8.70 (br, 1H), 4.32 (q, J ) 7.1, 4H), 4.15
(dd, J ) 11.5, 3.3 Hz, 2H), 4.05 (dd, J ) 12.1, 6.6 Hz, 2H),
2.18 (m, 1H), 1.45-1.20 (m, 14 H), 1.35 (t, J ) 7.1 Hz, 6H),
0.87 (t, J ) 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 159.8,
141.7, 110.7, 75.6, 60.7, 42.4, 31.8, 29.6, 29.4, 29.2, 28.0, 27.0,
22.5, 14.3, 13.9; FT-IR (CDCl3) 3446, 3022, 2980, 1700, 1653,
2,2-Dioctyl-1,3-p r op a n ed iol (37c). A clear oil (6.5 g, 65%)-
1
(lit.32); H NMR (300 MHz, CDCl3) 3.56 (d, J ) 4.4, 4H), 2.50
(s, 2H), 1.40-1.15 (m, 28H), 0.88 (t, J ) 6.6 Hz, 6H).
Gen er a l P r oced u r e for th e P r ep a r a tion of Ditosyla tes
38a , 38b, a n d 38c. To a solution of the diol (1.0 equiv) and
toluenesulfonyl chloride (2.0 equiv) in dichloromethane was
dropwise added a solution of triethylamine (2.5 equiv) and
4-(dimethylamino)pyridine (0.1 mol %) in dichloromethane at
room temperature. The reaction mixture was stirred for 3 h
and concentrated under reduced pressure. The residue was
dissolved in ether, washed with water several times, and dried
over MgSO4. The solvent was removed, and the residue was
used in the next step without further purification after
vacuum-drying.
1526, 1459 cm-1
.
Dieth yl 3,4-[2-(2-Eth ylh exyl)-1,3-p r op ylen ed ioxy]p yr -
r ole-2,5-d ica r boxyla te (41b). A pale yellow oil (2.53 g, 70%);
1H NMR (300 MHz, CDCl3) 8.65 (br, 1H), 4.37 (q, J ) 7.1, 4H),
4.24 (dd, J ) 12.1, 3.3 Hz, 2H), 3.97 (dd, J ) 12.1, 7.1 Hz,
2H), 2.30 (m, 1H), 1.36 (t, J ) 7.1 Hz, 6H), 1.40-1.22 (m, 11
H), 0.91-0.83 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 159.1,
140.9, 110.0, 75.3, 75.2, 59.9, 39.4, 35.4, 32.1, 31.4, 27.9, 25.2,
22.2, 13.6, 13.2, 9.7.
Diet h yl 3,4-(2,2-Dioct yl-1,3-p r op ylen ed ioxy)p yr r ole-
1
Dieth yl N-Ben zyl-3,4-d ih yd r oxyp yr r ole-2,5-d ica r boxy-
la te(39). The preparation of 39 is similar to that of 1. Colorless
crystals (hot methanol, 80%); mp 146 °C; 1H NMR (300 MHz,
CDCl3) 7.81 (s, 2H), 7.23 (m, 3H), 6.91 (m, 2H), 5.78 (s, 2H),
4.32 (q, J ) 7.1 Hz, 4H), 1.25 (t, J ) 7.1 Hz, 6H); 13C NMR (75
MHz, CDCl3) δ 162.8, 139.8, 139.3, 128.6, 127.1, 125.7, 111.2,
61.4, 49.5, 14.4. Anal. Calcd for C17H19NO6: C, 61.25; H, 5.75;
N, 4.20. Found: C, 61.00; H, 5.75; N, 4.21.
2,5-d ica r boxyla te (41c). A pale yellow oil (3.50 g, 65%); H
NMR (300 MHz, CDCl3) 8.61 (s, 1H), 4.33 (q, J ) 7.1, 4H),
3.94 (s, 4H), 1.35 (t, J ) 7.1 Hz, 6H), 1.45-1.18 (m, 28H), 0.87
(t, J ) 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 159.7, 142.0,
110.5, 79.2, 60.7, 43.8, 31.8, 30.4, 29.4, 29.2, 22.7, 22.6, 22.5,
14.3, 13.9; FT-IR (CDCl3) 3444, 2932, 2858, 1701, 1530, 1483,
1276 cm-1; HRMS (FAB) calcd for C29H49NO6 (MH+) 508.3638,
found 508.3641.
Gen er a l P r oced u r e for th e P r ep a r a tion of Dieth yl
N-Ben zyl-3,4-(2-a lk yl-1,3-p r op ylen ed ioxy)p yr r ole-2,5-d i-
ca r boxyla tes (40a , 40b, a n d 40c). To a mixture of diethyl
N-benzyl-3,4-dihydroxypyrrole-2,5-dicarboxylate (39) (7.5 g,
22.6 mmol) and ditosylate 38a (7.8 g, 22.6 mmol) in dry DMF
was added potassium carbonate (15.6 g, 0.1 mol) at room
temperature. The reaction mixture was stirred for 12 h at 110
°C under argon. After cooling to room temperature, the
reaction mixture was poured into ice water and extracted with
ether. The combined ether layers were dried over MgSO4 and
concentrated by rotary evaporator. Purification by chroma-
tography on silica gel using hexane/ethyl acetate (3:1) as eluent
afforded the product as pale yellow oil.
Hyd r olysis of 41a , 41b, a n d 41c. The procedure used is
the same as that used for the preparation of compound 13.
3,4-(2-Octyl-1,3-p r op ylen ed ioxy)p yr r ole-2,5-d ica r boxy-
lic Acid (42a ). A white powder (2.50 g, 92%); mp 165-167
1
°C; H NMR (300 MHz, DMSO-d6) 10.70 (br, 1H), 4.02 (dd, J
) 11.5, 2.7, 2H), 3.91 (dd, J ) 12.1, 6.0 Hz, 2H), 2.05 (m, 1H),
1.40-1.20 (m, 14H), 0.84 (t, J ) 7.1, 3H); HRMS (FAB) (MH+)
calcd for C17H26NO6 340.1760, found 340.1735. Anal. Calcd for
C
17H25NO6: C, 60.16; H, 7.42; N, 4.13. Found: C, 60.54; H,
7.67; N, 4.10.
3,4-[2-(2-E t h ylh exyl)-1,3-p r op ylen ed ioxy]p yr r ole-2,5-
d ica r boxylic Acid (42b). A white powder (2.20 g, 85%); mp
164-165 °C; 1H NMR (300 MHz, DMSO-d6) 10.70 (br, 1H),
4.02 (dd, J ) 12.0, 2.7, 2H), 3.85 (dd, J ) 12.0, 6.0 Hz, 2H),
2.10 (m, 1H), 1.40-1.17 (m, 11H), 0.89 (t, J ) 7.1 Hz, 3H),
0.86 (t, J ) 6.6, 3H); 13C NMR (75 MHz, DMSO-d6) δ 160.3,
140.6, 111.0, 74.8, 74.8, 39.5, 34.9, 32.1, 30.6, 27.8, 25.1, 22.2,
13.6, 10.1; HRMS (FAB) (MH+) calcd for C17H26NO6 340.1760,
found 340.1735. Anal. Calcd for C17H25NO6: C, 60.16; H, 7.42;
N, 4.13. Found: C, 60.07; H, 7.56; N, 3.98.
Dieth yl N-Ben zyl-3,4-(2-octyl-1,3-p r op ylen ed ioxy)p yr -
r ole-2,5-d ica r boxyla te (40a ). A pale yellow oil (8.2 g, 75%);
1H NMR (300 MHz, CDCl3) 7.20 (m, 3H), 6.90 (m, 2H), 5.90
(s, 2H), 4.26 (q, J ) 7.1 Hz, 4H), 4.21 (dd, J ) 8.2, 3.3 Hz,
2H), 3.98 (dd, J ) 12.1, 6.6 Hz, 2H), 2.22 (m, 1H), 1.50-1.20
(m, 14H), 1.26 (t, J ) 7.1 Hz, 6H), 0.88 (t, J ) 6.6 Hz, 3H).
Dieth yl N-Ben zyl-3,4-[2-(2-eth ylh exyl)-1,3-p r op ylen e-
d ioxy]p yr r ole-2,5-d ica r boxyla te (40b). A pale yellow oil
3,4-(2,2-Dioctyl-1,3-p r op ylen ed ioxy)p yr r ole-2,5-d ica r -
boxylic Acid (42c). A white powder (2.5 g, 85%); mp 125-
1
(7.80 g, 71%); H NMR (300 MHz, CDCl3) 7.21 (m, 3H), 6.91
1
(m, 2H), 5.90 (s, 2H), 4.26 (q, J ) 7.1 Hz, 4H), 4.22 (dd, J )
11.5, 2.7 Hz, 2H), 3.88 (dd, J ) 11.5, 7.1 Hz, 2H), 2.35 (m,
1H), 1.40-1.23 (m, 11H), 1.26 (t, J ) 7.1 Hz, 6H), 0.90 (t, J )
6.0 Hz, 3H), 0.86 (t, J ) 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δ 160.5, 142.6, 139.2, 128.2, 126.7, 126.1, 114.0, 75.9, 75.8, 60.4,
48.8, 40.0, 36.3, 32.9, 32.3, 28.7, 26.0, 23.0, 14.1, 13.9, 10.5.
Dieth yl N-Ben zyl-3,4-(2,2-d ioctyl-1,3-p r op ylen ed ioxy)-
p yr r ole-2,5-d ica r boxyla te (40c). A pale yellow oil (5.60 g,
127 °C; H NMR (300 MHz, DMSO-d6) 10.70 (s, 1H), 3.78 (s,
4H), 1.50-1.02 (m, 28H), 0.84 (t, J ) 7.1, 6H); FT-IR (CDCl3)
3280, 2928, 1700, 1653, 1093; HRMS (FAB) (MH+) calcd for
C
25H41NO6 452.3012, found 542.2987. Anal. Calcd for C25H41-
NO6: C, 66.49; H, 9.15; N, 3.10. Found: C, 66.42; H, 9.28; N,
2.98.
Deca r boxyla tion of th e Dia cid s 42a , 42b, a n d 42c. The
procedure used here is the same as that for the preparation
of N-benzyl-3,4-ethylenedioxypyrrole (17).
1
25%); H NMR (300 MHz, CDCl3) 7.20 (m, 3H), 6.85 (m, 2H),
5.89 (s, 2H), 4.24 (q, J ) 7.1 Hz, 4H), 3.90 (s, 4H), 1.50-1.10
(m, 34H), 0.87 (t, J ) 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3)
δ 160.9, 143.3, 137.7, 128.6, 127.1, 126.5, 114.2, 79.4, 61.0, 49.5,
44.4, 32.5, 32.4, 31.0, 30.0, 29.9, 23.5, 23.3, 14.6, 14.5; FT-IR
(CDCl3) 3023, 2965, 1716, 1437, 1365, 1291 cm-1; HRMS (FAB)
(MH+) calcd for C36H56NO6 598.4107, found 598.4114. Anal.
Calcd for C36H55NO6: C, 72.33; H, 9.27; N, 2.34. Found: C,
72.19; H, 9.41; N, 2.14.
3,4-(2-Octyl-1,3-p r op ylen ed ioxy)p yr r ole (43a ). An off-
white solid (1.20 g, 85%); mp 79-80 °C; H NMR (300 MHz,
1
CDCl3) δ 7.25 (br, 1H), 6.28 (d, J ) 3.3 Hz, 2H), 4.01 (dd, J )
11.5, 2.2, 2H), 3.85 (dd, J ) 11.6, 6.6 Hz, 2H), 2.05 (m, 1H),
1.50-1.20 (m, 14H), 0.88 (t, J ) 6.6 Hz, 3H); 13C NMR (75
MHz, CDCl3) δ 139.4, 103.1, 76.7, 43.6, 31.8, 29.8, 29.4, 29.2,
27.4, 27.1, 22.5, 13.9; FT-IR (CDCl3) 3489, 3021, 2963, 2931,
1653, 1545, 1495, 1380 cm-1; HRMS (FAB) (MH+) calcd for
Deben zyla tion of 40a , 40b, a n d 40c. A reaction mixture
of 40a (5.0 g, 10.3 mmol), anisole (1.5 g, 13.4 mmol), and H2-
SO4 (0.7 g, 7.0 mmol) in trifluroacetic acid was refluxed for
C15H26NO2 252.1963, found 252.1963. Anal. Calcd for C15H25-
NO2: C, 71.67; H, 10.02; N, 5.57. Found: C, 71.76; H, 9.94; N,
5.19.