Synthesis of 5,6ꢀindoloꢀ12ꢀcrownsꢀ4
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 1, January, 2002
137
2 ArOCH2); 7.18 (s, 1 H, H(14)); 7.39—7.47 (m, 3 H, H(3´),
H(4´), H(5´)); 7.51—7.59 (m, 2 H, H(2´), H(6´)); 7.92 (br.s,
1 H, NH); 8.19 (s, 1 H, H(11)). IR, ν/cm–1: 1659 (C=O); 2213
(C≡C); 3285 (NH). Found (%): C, 69.27; H, 6.06; N, 3.74.
C22H23NO5. Calculated (%): C, 69.27; H, 6.08; N, 3.67.
Compounds 4b,c,e were prepared analogously to comꢀ
pound 4a.
Nꢀ{13ꢀ[2ꢀ(4ꢀMethoxyphenyl)ethynyl]ꢀ2,3,5,6,8,9ꢀhexaꢀ
hydroꢀ1,4,7,10ꢀtetraoxabenzocyclododecenꢀ12ꢀyl}acetamide
(4b). The yield was 82%, m.p. 85—87 °C (benzene—hexane).
1H NMR (CDCl3), δ: 2.26 (s, 3 H, Me); 3.80—3.95 (m, 11 H,
4 OCH2, OMe); 4.18—4.29 (m, 4 H, 2 ArOCH2); 6.95 (d, 2 H,
H(3´), H(5´), J = 8.3 Hz); 7.15 (s, 1 H, H(4)); 7.49 (d, 2 H,
H(2´), H(6´), J = 8.3 Hz); 7.91 (br.s, 1 H, NH); 8.18 (s, 1 H,
H(11)). IR, ν/cm–1: 1660 (C=O); 2218 (C≡C); 3287 (NH).
Found (%): C, 66.71; H, 5.80; N, 3.47. C23H25NO6. Calcuꢀ
lated (%): C, 67.14; H, 6.12; N, 3.40.
dried with Na2SO4 and filtered through a layer of Al2O3
(2.5×2 cm) The solvent was removed in vacuo and the residue
was recrystallized from benzene. Compound 4f was obtained in
1
a yield of 0.2 g (83%), m.p. 151—152.5 °C. H NMR (CDCl3),
δ: 2.24 (s, 3 H, Me); 3.47 (s, 1 H, C≡CH); 3.78—3.97 (m, 8 H,
4 OCH2); 4.15—4.29 (m, 4 H, 2 ArOCH2); 7.12 (s, 1 H, H(14));
7.83 (br.s, 1 H, NH); 8.16 (s, 1 H, H(11)). IR, ν/cm–1: 1666
(C=O); 2095 (C≡C); 3263 (≡C—H); 3337 (NH). Found (%):
C, 62.89; H, 6.21; N, 4.84. C16H19NO5. Calculated (%):
C, 62.94; H, 6.27; N, 4.59.
13ꢀPhenylꢀ2,3,5,6,8,9ꢀhexahydroꢀ12Hꢀ[1,4,7,10]tetraoxaꢀ
cyclododeceno[2,3ꢀf ]indole (5a). KOH (10 mg, 0.17 mmol) was
added to a suspension of compound 4a (0.1 g, 0.26 mmol) in
95% EtOH (5 mL). The reaction mixture was refluxed for
3 h, diluted with water (15 mL), and extracted with CHCl3
(3×10 mL). The organic extracts were dried with Na2SO4 and
filtered through a layer of Al2O3 (2.5×2 cm). The solvent was
removed in vacuo and the residue was recrystallized from a benꢀ
zene—hexane mixture. Compound 5a was obtained in a yield of
70 mg (70%), m.p. 48—49 °C. 1H NMR (CDCl3), δ: 3.78—3.95
(m, 8 H, 4 OCH2); 4.15—4.29 (m, 4 H, 2 ArOCH2); 6.36 (s,
1 H, H(14)); 7.09 (s, 1 H, H(15)); 7.18 (s, 1 H, H(11));
7.34—7.41 (m, 3 H, H(3´), H(4´), H(5´)); 7.50—7.56 (m, 2 H,
H(2´), H(6´)). IR, ν/cm–1: 3347 (NH). MS, m/z (Irel (%)):
339.9 [M]+ (22), 338.8 (100), 251.0 (31), 195.0 (39), 126.0 (9).
Highꢀresolution mass spectrum. Found: m/z 339.1465 [M]+.
Nꢀ{13ꢀ[2ꢀ(4ꢀNitrophenyl)ethynyl]ꢀ2,3,5,6,8,9ꢀhexahydroꢀ
1,4,7,10ꢀtetraoxabenzocyclododecenꢀ12ꢀyl}acetamide (4c). The
yield was 66%, m.p. 199—200.5 °C (benzene—CHCl3). 1H NMR
(CD2Cl2), δ: 2.22 (s, 3 H, Me); 3.75—3.89 (m, 8 H, 4 OCH2);
4.13—4.24 (m, 4 H, 2 ArOCH2); 7.18 (s, 1 H, H(14)); 7.69 (d, 2
H, H(2´), H(6´), J = 8.6 Hz); 7.69 (br.s, 1 H, NH); 8.09 (s, 1 H,
H(11)); 8.25 (d, 2 H, H(3´), H(5´), J = 8.6 Hz). IR, ν/cm–1
:
1664 (C=O); 2212 (C≡C); 3278 (NH). Found (%): C, 61.77;
H, 5.45; N, 6.21. C22H22N2O7. Calculated (%): C, 61.96;
H, 5.20; N, 6.57.
C
20H21NO4. Calculated: M = 339.14705.
Nꢀ{13ꢀ[2ꢀ(Trimethylsilyl)ethynyl]ꢀ2,3,5,6,8,9ꢀhexahydroꢀ
1,4,7,10ꢀtetraoxabenzocyclododecenꢀ12ꢀyl}acetamide (4e). The
yield was 41%, m.p. 130—131.5 °C (benzene—hexane). 1H NMR
(CDCl3), δ: 0.32 (s, 9 H, SiMe3); 2.23 (s, 3 H, Me); 3.75—3.89
(m, 8 H, 4 OCH2); 3.77—3.95 (m, 4 H, 2 ArOCH2); 7.08 (s,
1 H, H(14)); 7.92 (br.s, 1 H, NH); 8.15 (s, 1 H, H(11)). IR,
ν/cm–1: 1694 (C=O); 2141 (C≡C); 3388 (NH). Found (%):
C, 60.89; H, 7.30; N, 3.89. C19H27NO5Si. Calculated (%):
C, 60.45; H, 7.21; N, 3.71.
Compounds 5b,c,f were prepared analogously to comꢀ
pound 5a.
13ꢀ(4ꢀMethoxyphenyl)ꢀ2,3,5,6,8,9ꢀhexahydroꢀ12Hꢀ
[1,4,7,10]tetraoxacyclododeceno[2,3ꢀf ]indole (5b). The yield
was 55%, m.p. 218—220 °C (benzene). 1H NMR (CDCl3), δ:
3.73—3.95 (m, 11 H, 4 OCH2 and OMe); 4.17—4.26 (m, 4 H,
2 ArOCH2); 6.63 (s, 1 H, H(14)); 6.96—7.5 (m, 3 H, H(3´),
H(5´), H(15)); 7.23 (s, 1 H, H(11)); 7.57 (d, 2 H, H(2´),
H(6´), J = 8.4 Hz); 8.12 (br.s, 1 H, NH). IR, ν/cm–1: 3424
(NH). MS, m/z (Irel (%)): 369.0 [M]+ (100), 281.1 (38), 225.1
(41), 140.5 (15). Highꢀresolution mass spectrum. Found:
m/z 369.1580 [M]+. C21H23NO5. Calculated: M = 369.15761.
13ꢀ(4ꢀNitrophenyl)ꢀ2,3,5,6,8,9ꢀhexahydroꢀ12Hꢀ
[1,4,7,10]tetraoxacyclododeceno[2,3ꢀf ]indole (5c). The yield
was 70%, m.p. 251—253 °C (AcOEt). 1H NMR (DMSOꢀd6), δ:
3.68—3.95 (m, 8 H, 4 OCH2); 4.15—4.28 (m, 4 H, 2 ArOCH2);
7.07 (s, 1 H, H(14)); 7.55 (d, 2 H, H(2´), H(6´), J = 8.5 Hz);
7.61 (s, 1 H, H(15)); 8.02 (s, 1 H, H(11)); 8.25 (d, 2 H, H(3´),
H(5´), J = 8.5 Hz). IR, ν/cm–1: 3385 (NH). MS, m/z (Irel (%)):
384.0 [M]+ (65), 378.8 (100), 236.0 (31), 175.0 (39), 116.0 (9).
Highꢀresolution mass spectrum. Found: m/z 384.1320 [M]+.
Nꢀ{13ꢀ[2ꢀ(4ꢀFormylphenyl)ethynyl]ꢀ2,3,5,6,8,9ꢀhexahydroꢀ
1,4,7,10ꢀtetraoxabenzocyclododecenꢀ12ꢀyl}acetamide (4d). A
mixture of iodide 2 (0.2 g, 0.5 mmol), 4ꢀethynylbenzaldehyde
(3d) (60 mg, 0.5 mmol), Pd(OAc)2 (20 mg, 0.089 mmol), PPh3
(60 mg, 0.23 mmol), and CuI (10 mg, 0.053 mmol) in Et3N
(0.5 mL) and benzene (5 mL) was stirred under Ar at 70—75 °C
for 1 h. After completion of the reaction, the cooled mixture was
filtered through a layer of SiO2 (2.5×2 cm), the solvent was
removed in vacuo, and the residue was recrystallized from a
benzene—hexane mixture. Compound 4d was obtained in a yield
1
of 0.12 g (60%), m.p. 129—131 °C. H NMR (CDCl3), δ: 2.29
(s, 3 H, Me); 3.80—3.95 (m, 8 H, 4 OCH2); 4.18—4.30 (m, 4 H,
2 ArOCH2); 7.19 (s, 1 H, H (14)); 7.68 (d, 3 H, H(2´), H(6´),
J = 8.3 Hz); 7.83 (br.s, 1 H, NH); 7.97 (d, 3 H, H(3´), H(5´),
J = 8.3 Hz); 8.17 (s, 1 H, H(11)); 10.08 (s, 1 H, CHO). IR,
ν/cm–1: 1697 (CHO); 1661 (NHC=O); 2205 (C≡C); 3275 (NH).
Found (%): C, 67.34; H, 6.66; N, 4.01. C23H23NO6. Calcuꢀ
lated (%): C, 67.46; H, 6.66; N, 3.42.
Nꢀ(13ꢀEthynylꢀ2,3,5,6,8,9ꢀhexahydroꢀ1,4,7,10ꢀtetraoxaꢀ
benzocyclododecenꢀ12ꢀyl)acetamide (4f). Potassium carbonate
(14 mg, 0.1 mmol) was added to a solution of compound 4e
(0.13 g, 0.8 mmol) in 95% EtOH (5 mL). The reaction mixture
was stirred at ∼20 °C for 3 h, diluted with water (30 mL), and
extracted with CHCl3 (3×15 mL). The organic extracts were
C
20H20N2O6. Calculated: M = 384.13412.
2,3,5,6,8,9ꢀHexahydroꢀ12Hꢀ[1,4,7,10]tetraoxacyclododeꢀ
ceno[2,3ꢀf]indole (5f). Compound 5f was prepared from 4e in
75% yield and from 4f in 33% yield, m.p. 180—182 °C (benꢀ
zene—hexane). 1H NMR (CDCl3), δ: 3.75—4.00 (m, 8 H,
4 OCH2); 4.15—4.22 (m, 4 H, 2 ArOCH2); 6.47 (d, 1 H,
H(14), J = 2.5 Hz); 7.04 (s, 1 H, H(15)); 7.16 (d, 1 H, H(13),
J = 2.5 Hz); 7.27 (s, 1 H, H(11)); 8.05 (br.s, 1 H, NH). IR,
ν/cm–1: 3347 (NH). MS, m/z (Irel (%)): 263.0 [M]+ (100),
175.1 (81), 119.0 (77), 91.0 (21). Highꢀresolution mas specꢀ
trum. Found: m/z 263.1149 [M]+. C14H17NO4. Calculated:
M = 263.11575.