S.M. Bhosale et al. / Tetrahedron 68 (2012) 6420e6426
6425
120.26, 122.13, 125.30, 135.04, 138.58, 138.95, 154.67, 189.21; Ms
(70 eV) m/z 291(85), 289(24), 230(30), 232(32), 154(40), 151(38),
124(25), 126(27), 91(100%).
(1H, s, OeCHeO), 5.85 (2H, s, OCH2Ph), 6.75 (1H, d, J¼8.6 Hz, ArH),
7.07 (1H, d, J¼7.2 Hz, ArH), 7.18e7.45 (9H, m, ArH), 7.56 (2H, d,
J¼7.1 Hz, ArH), 7.63 (1H, d, J¼8.6 Hz, ArH), 8.40 (1H, d, J¼7.2 Hz,
ArH); 13C NMR (75 MHz, CDCl3)
d 25.42, 29.66, 48.80, 67.17, 70.05,
4.1.15. 9-Benzyl-4-(benzyloxy)-3-bromo-9H-carbazole-1-
carbaldehyde (18). To a stirred solution of compound 17 (1 g,
3.44 mmol) in dry DMF (15 ml) at 0 ꢀC was added NaH (60% dis-
persion in mineral oil, 0.330 g, 8.6 mmol). The mixture was stirred
for 30 min at 0 ꢀC and allowed to warm to room temperature.
Benzyl bromide (0.409 ml, 3.44 mmol) was then added and the
mixture was stirred for an additional 1 h. After quenching with
water (100 ml) it was extracted several times with CH2Cl2 and the
combined organic layer was dried over anhydrous Na2SO4. Filtrate
was concentrated under reduced pressure and the residue was
purified by column chromatography (3% ethyl acetate/hexane as an
eluent), which gave white product 18 (1.52 g, 94%); mp 190 ꢀC;
[Found C, 69.20; H, 4.67; N, 2.59. C27H20BrNO2 requires C, 68.95; H,
100.00, 101.29, 108.71, 113.61, 114.83, 119.81, 122.37, 123.06, 125.04,
125.52, 125.96, 126.83, 127.44, 127.84, 128.31, 128.55, 128.65, 128.71,
128.77,135.68, 137.21, 138.66,139.36,140.89,155.77; Ms (70 eV) m/z
463(60), 437(48), 405(10), 379(57), 314(70%) 409(20), 91(100%).
4.1.18. 9-Benzyl-3-methyl-9H-carbazole-1,4-dione (16). To a stirred
solution of compound 20 (0.5 g, 1.07 mmol) in methanol were
added catalytic amount of H2SO4 and H2O2 (1.51 ml 40% in water,
1.61 mmol). Reaction was refluxed for 30 min, brought to room
temperature and neutralized by addition of Na2CO3. Reaction
mixture was extracted with ethyl acetate (3ꢂ50 ml). Combined
organic layer was dried on Na2SO4, concentrated on rota evaporator
and purified by column chromatography using 6% ethyl acetate in
hexane as an eluent system, which gave red colored solid product
16 (0.243 g, 75%).
4.29; N, 2.98]; Rf (20% ethyl acetate/hexane) 0.65; FTIR (KBr cmꢁ1
)
2870, 2765, 1670; 1H NMR (300 MHz, CDCl3)
d
5.26 (2H, s, NCH2),
5.88 (2H, s, eOCH2), 6.94e6.96(2H, m, ArH), 7.18e7.31 (4H, m, ArH),
7.33e7.47 (5H, m, ArH), 7.63e7.66 (d, 2H, J¼6.7 Hz, ArH), 8.05 (1H, s,
ArH), 8.21e8.24 (1H, d, J¼7.9 Hz, ArH), 9.98(1H, s, eCHO); 13C NMR
4.1.19. 1-Bromo-3-formyl-9H-carbazol-4-yl trifluoromethanesulfonate
(21). To a stirring solution of compound 11 (0.5 g,1.73 mmol) in DCM
at 0 ꢀC was added triethyl amine (0.175 ml,1.73 mmol). Reaction was
continued for 15 min at same temperature and then triflic anhydride
(0.583 g, 2.07 mmol) was added slowly. After 2 h reaction was neu-
tralized by addition of water and extracted with ethyl acetate
(3ꢂ50 ml). Combined organic layer was washed with brine and dried
on anhydrous Na2SO4. After evaporation of organic layer the residue
was chromatographed using 4% ethyl acetate/hexane as an eluent
system, which gave white colored product 21 (0.657 g, 90%). mp
220 ꢀC (decomposed); Found [C, 39.50; H, 1.95; N, 3.63.
C14H7BrF3NO4S requires C, 39.83; H, 1.67; N, 3.32]; Rf (20% ethyl ace-
(75 MHz, CDCl3)
d 50.36, 74.85, 106.53, 109.83, 119.53, 120.42,
120.69, 121.40, 122.87, 125.83, 127.20, 127.46, 128.25, 128.50, 128.65,
128.83, 136.05, 136.24, 136.68, 140.19, 141.72, 156.06, 188.14; Ms
(70 eV) m/z 471(75), 469(720), 378(55), 350(45), 91(65), 77(100),
44(80%).
4.1.16. 9-Benzyl-4-(benzoloxy)-3-bromo-1-(1,3-dioxan-2-yl)-9H-
carbazole (19). To a solution of compound 18 (1 g, 2.10 mmol) in
toluene was added catalytic amount of pTSA and reaction was
subjected for reflux with Dean Stark apparatus for 5 h. Reaction was
cooled and neutralized by addition of saturated aq Na2CO3 (10 ml).
Then reaction mixture was extracted by ethyl acetate (3ꢂ50 ml).
Combined organic layer was dried over Na2SO4, concentrated on
rota evaporator and purified by column chromatography using 5%
ethyl acetate/hexane as an eluent system, which gave compound 19
(0.896 g, 80%). mp 185 ꢀC; [Found C, 67.90; H, 4.50; N, 3.00.
C30H26BrNO3 requires C, 68.19; H, 4.96; N, 2.65]; Rf (30% ethyl ac-
etate/hexane) 0.61; FTIR (KBr cmꢁ1) 1670, 1210; 1H NMR (300 MHz,
1
tate/hexane) 0.61; FTIR (KBr cmꢁ1) 3431, 1668; H NMR (300 MHz,
CDCl3)
(1H, d, J¼8.3 Hz, ArH), 8.24 (1H, s, ArH),10.09(1H, s, eCHO),12.60(1H,
br, NH);13C NMR (75MHz, CDCl3)
77.19,104.59,111.74,116.53,117.55,
d
7.39e7.44 (1H, t, J¼7.1 Hz, ArH), 7.61e7.75 (2H, m, ArH), 8.15
d
120.88, 122.20, 122.49, 123.62, 128.34, 128.60, 139.43, 143.15, 143.58,
184.95; Ms (70 eV) m/z 423(12), 421(15), 290(32), 288(30), 153(22),
151(17), 69(100%).
CDCl3)
d
1.25e1.52 (2H, m, OCH2eCH2eCH2O), 3.72e3.80 (2H, m,
4.1.20. 1-Bromo-9H-carbazole-3-carbaldehyde (22). To a solution of
compound 21 (0.5 g, 1.18 mmol) in dry DMF kept under N2 atmo-
sphere were added tetrakis(triphenylphosphine)palladium
(0.134 g, 10 mol %) and tributyl tin hydride (0.344 g, 1.18 mmol).
Reaction mixture was heated at 100 ꢀC for 45 min. After con-
sumption of starting material water was added to the reaction
mixture and extracted with ethyl acetate (3ꢂ25 ml). Combined
organic layer was washed with brine and dried on anhydrous
Na2SO4. The residue obtained after evaporation of organic layer was
chromatographed using 5% ethyl acetate/hexane as an eluent sys-
tem, which gave white colored product 22 (0.252 g, 78%); mp
210 ꢀC; [Found C, 57.21; H, 3.19; N, 5.48. C13H8BrNO requires C,
56.96; H, 2.94; N, 5.11]; Rf (30% ethyl acetate/hexane) 0.65; FTIR
OCH2), 4.08e4.13 (2H, m, OCH2), 5.20 (2H, s, NCH2), 5.71 (1H, s,
OeCHeO), 5.78 (2H, s, OCH2Ph), 7.03e7.19 (2H, m, ArH), 7.20e7.30
(5H, m, ArH), 7.35e7.49 (4H, m, ArH), 7.69e7.96 (2H, m, ArH), 7.96
(1H, s, ArH), 8.26e8.29 (1H, m, ArH); 13C NMR (75 MHz, CDCl3)
d
25.32, 48.74, 67.15, 74.45, 98.52, 106.14, 109.20, 106.14, 109.20,
119.2, 119.30, 120.37, 120.99, 122.69, 125.35, 126.37, 127.10, 128.21,
128.24, 128.56, 128.84, 129.10, 136.93, 138.04, 138.69, 141.48, 151.59.
4.1.17. 9-Benzyl-4-(benzyloxy)-1-(1,3-dioxan-2-yl)-3-methyl-9H-
carbazole (20). To a stirred solution of compound 19 (0.5 g,
0.946 mmol) in dry THF at ꢁ10 ꢀC was added slowly n-butyl lithium
(1.42 mmol). Stirring was continued for 30 min at the same tem-
perature and then, reaction temperature was decreased to ꢁ40 ꢀC
and iodomethane (0.07 ml, 1.13 mmol) was added. Reaction was
continued for 1 h at the same temperature and then slowly brought
to room temperature. Reaction mixture was neutralized by 15 ml
saturated aq NH4Cl and extracted with ethyl acetate (3ꢂ30 ml).
Combined organic layer was dried on Na2SO4, concentrated on rota
evaporator and purified by column chromatography using 6% ethyl
acetate in hexane as an eluent system, which gave product 20
(0.395 g, 90%). mp 160 ꢀC; [Found C, 80.00; H, 6.52; N, 3.30.
C31H29NO3 requires C, 80.32; H, 6.31; N, 3.02]; Rf (30% ethyl acetate/
hexane) 0.48; FTIR (KBr cmꢁ1) 1650, 1630, 1180; 1H NMR (300 MHz,
(KBr cmꢁ1) 3204, 1673; 1H NMR (300 MHz, CDCl3)
d 7.33e7.39 (1H,
m, ArH), 7.51e7.56 (2H, m, ArH), 8.11e8.13 (2H, m, ArH), 8.53 (1H, s,
ArH), 8.59 (1H, br, NH),10.04 (1H, s, CHO); 13C NMR (75 MHz, CDCl3)
d
104.80,111.58,121.17,121.40,122.88,123.72,124.39,127.59,128.86,
130.36, 139.50, 141.65, 190.55; Ms (70 eV) m/z 275(80), 273(90),
246(50), 244(50), 166(20), 165(15), 164(55), 139(34), 137(30),
91(100), 82(60), 69(35%).
4.1.21. 1-Methoxy-9H-carbazole-3-carbaldehyde (5). To a solution of
compound 22 (0.2 g,1.00 mmol) in dry DMF were added CuI (0.133 g,
1.00 mmol) and sodium methoxide (1.08 g, 20.40 mmol) in methanol
(5 ml). Reaction was degassed by nitrogen and kept at 120 ꢀC for 5 h.
It was then quenched by addition of water (50 ml). Reaction mixture
CDCl3)
d 1.25e1.42 (5H, m, OCH2eCH2eCH2O & CH3), 3.74e3.81
(2H, m, OCH2), 4.07e4.12 (2H, m, OCH2), 5.36 (2H, s, NCH2), 5.71