Synthesis of pyrano[2,3-c]carbazoles, pyrano[3,2-b]carbazoles and furo[3,2-b]carbazole derivatives via iodocyclization

Article abstract of DOI:10.1007/s12039-011-0181-5

A simple and facile synthesis of pyranocarbazole derivatives starting from easily accessible O-propargylated carbazoles using iodocyclization in good yields is reported. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s12039-011-0181-5

c
J. Chem. Sci. Vol. 124, No. 2, March 2012, pp. 487–494. ꢀ Indian Academy of Sciences.
Synthesis of pyrano[2,3-c]carbazoles, pyrano[3,2-b]carbazoles
and furo[3,2-b]carbazole derivatives via iodocyclization
KRISHNA CHAITANYA TALLURI and RAJAGOPAL NAGARAJAN∗
School of Chemistry, University of Hyderabad, Hyderabad 500046, India
e-mail: rnsc@uohyd.ernet.in
MS received 3 August 2011; revised 13 September 2011; accepted 15 September 2011
Abstract. A simple and facile synthesis of pyranocarbazole derivatives starting from easily accessible
O-propargylated carbazoles using iodocyclization in good yields is reported.
Keywords. Carbazole; pyranocarbazole; furocarbazole; iodocyclization; O-propargylcarbazole.
1. Introduction
2. Experimental
Carbazole alkaloids have attracted the attention of syn- 2.1 General procedure for O-propargylated
thetic chemists due to their easily accessible struc- carbazoles
tural features and promising biological applications.1
An oven dried 100 mL round bottom flask equipped
with a teflon coated magnetic stirring bar was charged
with hydroxycarbazole (5 mmol), potassium carbon-
ate (15 mmol) in 15 mL of acetone under stirring.
After stirring for 30 min., propargyl bromide (6 mmol)
was added slowly and reaction mass was stirred at
room temperature for 6 h. Reaction mass was poured
into water, neutralized with 0.1 M HCl, extracted with
ethyl acetate, washed twice with water (50 mL × 2),
dried for an hour, sodium sulfate and solvent was
removed under vacuum to sulfate the corresponding
O-propargylated carbazole as a low melting solid.
Among these, pyranocarbazole alkaloids form a promi-
nent group due to their occurrence in various plant
sources and also their intriguing structural features.2
Pyrayafolines, eustifolines, clausamines, clausevatines,
etc. are some of the important pyranocarbazole alka-
loids that have been synthesized in recent times2
(figure 1). Clausamines have been reported to inhibit
EBV activation in Raji cells.3 Diaryl pyranocarbazole
derivatives were reported to show photochromic prop-
erties.4 In this context, an efficient methodology for
the synthesis of these pyranocarbazole derivatives is
desirable.
The synthesis of benzopyran and quinoline deriva-
tives from the corresponding propargyl derivatives has
attracted synthetic chemists in recent times.5,6 Larock
and co-workers reported a simple methodology for
the synthesis of benzopyrans through iodocyclization.7
These reactions involve readily available reagents like
iodine and simple bases which are inexpensive and
ecofriendly. These reactions are also very efficient,
clean and do not require harsh conditions. Further, these
products can be useful building blocks for the synthesis
of fused heterocycles.
2.1a 9-Ethyl-1,4-dimethyl-3-(prop-2-ynyloxy)-9H-
carbazole (2a): mp: 72–74◦C; IR(KBr): 3273, 2968,
2920, 2870, 2125, 1581, 1512, 1464, 1371, 1302, 1261,
1
1197, 1140, 1070, 1026, 792, 744, 540, 432 cm−1; H
NMR (400 MHz, CDCl3, TMS) δ 8.24 (d, J = 8.0 Hz,
1H), 7.46–7.40 (m, 2H), 7.22 (t, J = 7.6 Hz, 1H), 6.99
(s, 1H), 4.72 (s, 2H), 4.58 (q, J = 6.8 Hz, 2H), 2.81 (s,
6H), 2.51 (s, 1H), 1.41 (t, J = 6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3, TMS) δ 148.7, 141.5, 125.1, 124.1,
123.3, 122.9, 120.8, 120.4, 118.6, 118.4, 117.4, 108.4,
79.7, 74.9, 59.5, 39.3, 20.0, 15.4, 12.9; m/z = 277,
positive mode; Anal. Calcd for C19H19NO: C, 82.28; H,
6.90; N, 5.05%; found: C, 82.11; H, 6.85; N, 5.12%.
2.1b 9-Ethyl-3-(prop-2-ynyloxy)-9H-carbazole (2b):
∗For correspondence
mp: 66–68◦C; IR(KBr): 3287, 3051, 2976, 2932, 2121,
487

488
Talluri Krishna Chaitanya and Rajagopal Nagarajan
minutes at room temperature. Pd(PPh3)2Cl2 (2 mol%)
and CuI (1 mol%) were added under nitrogen and the
the reaction mixture was stirred at room temperature
for 4 h, after which time TLC (95:05 hexanes:ethyl
acetate) indicated complete conversion. Reaction mass
was filtered through celite. The filterate was poured
into crushed ice slowly and extracted with ethyl acetate.
The organic layer was washed with water and brine,
dried over anhydrous sodium sulfate and solvent was
removed under reduced pressure. The crude material
was purified by column chromatography (eluent: 5–
15% ethyl acetate in hexanes) using silica gel (100–200
mesh).
Figure 1. Pyranocarbazole alkaloids.
1622, 1579, 1485, 1323, 1292, 1230, 1180, 1086, 1060,
1
1024, 923, 856, 802, 746 cm−1; H NMR (400 MHz,
2.2a 9-Ethyl-3-(3-phenylprop-2-ynyloxy)-9H-carbazole (3a):
mp: 120–122◦C; IR(KBr): 3043, 2974, 2854, 1626,
1595, 1483, 1471, 1444, 1371, 1321, 1288, 1230, 1190,
CDCl3, TMS) δ 8.15 (d, J = 7.6 Hz, 1H), 7.78 (s, 1H),
7.52 (t, J = 6.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 7.35
(d, J = 8.8 Hz, 1H), 7.27–7.24 (m, 2H), 4.86 (s, 2H),
4.33 (q, J = 7.2 Hz, 2H), 2.61 (s, 1H), 1.44 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3, TMS) δ
151.5, 140.6, 135.7, 125.8, 123.2, 122.7, 120.5, 118.5,
115.7, 109.2, 108.7, 105.8, 79.4, 75.4, 57.3, 37.6, 13.9;
m/z = 250, positive mode; Anal. Calcd for C17H15NO:
C, 81.90; H, 6.06; N, 5.62%; found: C, 81.85; H,
6.12; N, 5.56%.
1
1151, 1008, 844, 800, 748, 690, 420 cm−1; H NMR
(400 MHz, CDCl3, TMS) δ 8.11 (d, J = 7.6 Hz, 1H),
7.80 (s, 1H), 7.50 (m, 3H), 7.42–7.22 (m, 7H), 5.05
(s, 2H), 4.35 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3, TMS) δ 151.8,
140.6, 135.6, 131.9, 128.3, 125.7, 123.3, 122.8, 122.6,
120.5, 119.1, 118.5, 115.8, 109.1, 108.6, 105.9, 87.1,
84.7, 58.2, 37.6, 13.9; m/z = 326, positive mode; Anal.
Calcd for C23H19NO: C, 84.89; H, 5.89; N, 4.30%;
found: C, 84.66; H, 5.81; N, 4.28%.
2.1c 9-Benzyl-3-(prop-2-ynyloxy)-9H-carbazole (2c):
mp: 102–104◦C; IR(KBr): 3283, 3065, 3024, 2912,
2852, 2127, 1626, 1597, 1489, 1448, 1381, 1354, 1325,
2.2b 9-Benzyl-3-(3-p-tolylprop-2-ynyloxy)-9H-carbazole (3b):
mp: 140–142◦C; IR(KBr): 3028, 2916, 2229, 1604,
1510, 1493, 1475, 1356, 1323, 1246, 1222, 1174, 1055,
1
1188, 1057, 966, 933, 893, 848, 802 cm−1; H NMR
(400 MHz, CDCl3, TMS) δ 8.10 (d, J = 7.6 Hz, 1H),
7.73 (s, 1H), 7.43 (t, J = 7.2 Hz, 1H), 7.35 (d, J =
8.4 Hz, 1H), 7.22–7.26 (m, 5H), 7.13–7.15 (m, 3H), 5.5
(s, 2H), 4.8 (s, 2H), 2.55 (d, J = 2.0 Hz, 1H); 13C
NMR (100 MHz, CDCl3, TMS) δ 151.7, 141.3, 137.2,
136.3, 128.8, 127.5, 126.4, 126.0, 123.3, 122.8, 120.4,
118.9, 115.8, 109.6, 109.0, 105.6, 79.2, 75.3, 57.2, 46.7;
m/z = 312, positive mode; Anal. Calcd for C22H17NO:
C, 84.86; H, 5.50; N, 4.50%; found: C, 84.95; H,
5.56; N, 4.39%.
1
1026, 909 cm−1; H NMR (400 MHz, CDCl3, TMS)
δ 8.15 (d, J = 8.0 Hz, 1H), 7.84 (s, 1H), 7.47 (t,
J = 8.0 Hz, 1H), 7.42–7.37 (m, 3H), 7.31–7.26 (m,
5H), 7.23 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.18–7.14
(m, 4H), 5.50 (s, 2H), 5.05 (s, 2H), 2.38 (s, 3H); 13C
NMR (100 MHz, CDCl3, TMS) δ 152.1, 141.3, 138.8,
137.3, 136.3, 131.8, 129.1, 128.8, 127.5, 126.4, 126.0,
123.4, 122.9, 120.5, 119.5, 118.9, 116.0, 109.6, 109.0,
105.8, 87.3, 83.9, 58.2, 46.7, 21.5; m/z = 402, positive
mode; Anal. Calcd for C29H23NO: C, 86.75; H, 5.77; N,
3.49%; found: C, 86.67; H, 5.72; N, 3.41%.
2.2 General procedure for Sonogashira coupling
of O-propargylatedcarbazoles with aryl iodides
2.2c 9-Benzyl-3-(3-(4-nitrophenyl)prop-2-ynyloxy)-
9H-carbazole (3c): mp: 154–156◦C; IR(KBr): 3088,
3024, 2924, 2856, 1626, 1591, 1487, 1467, 1448, 1379,
1344, 1286, 1238, 1215, 1184, 1059, 895, 817, 723,
An oven dried 50 mL Schlenk tube equipped with a
teflon coated magnetic stirring bar was charged with
O-propargylated carbazole (2 mmol), 1 g of molecu-
lar sieves and aryl iodide (2.2 mmol). The tube was
evacuated and filled with nitrogen. To it, 10 mL of dry
THF and 5 mL of freshly distilled triethylamine were
added under nitrogen and the reaction was stirred for 10
1
607, 424 cm−1; H NMR (400 MHz, CDCl3, TMS) δ
8.17 (d, J = 8.4 Hz, 2H), 8.13 (d, J = 7.6 Hz, 1H),
7.80 (d, J = 2.0 Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H),
7.45 (t, J = 8.8 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H),

Pyranocarbazole derivatives
489
7.26–7.30 (m, 5H), 7.22–7.16 (m, 3H), 5.50 (s, 2H), 2.2g 9-Ethyl-1,4-dimethyl-3-(3-p-tolyl prop-2-ynyloxy)-
5.07 (s, 2H); 13C NMR (100 MHz, CDCl3, TMS) δ 9H-carbazole (3g): mp: 148–150◦C; IR(KBr): 3020,
151.8, 147.3, 141.3, 137.2, 136.4, 132.5, 129.2, 128.8, 2925, 2230, 1600, 1475, 1355, 1240, 1225, 1170, 1056,
1
127.5, 126.4, 126.1, 123.5, 123.4, 122.7, 120.4, 119.0, 1021, 911 cm−1; H NMR (400 MHz, CDCl3, TMS) δ
115.8, 109.7, 109.1, 105.8, 90.0, 85.2, 57.9, 46.7; m/z = 8.36 (d, J = 7.2 Hz, 1H), 7.61 (d, J = 7.2 Hz, 1H), 7.50
433, positive mode; Anal. Calcd for C28H20N2O3: C, (t, J = 7.6 Hz, 1H), 7.44 (d, J = 6.8 Hz, 1H), 7.41–
77.76; H, 4.66; N, 6.48%; found: C, 77.62; H, 4.61; N, 7.39 (m, 2H), 7.30–7.25 (m, 1H), 7.16–7.12 (m, 2H),
6.56%.
4.90 (s, 2H), 4.60 (q, J = 7.0 Hz, 2H), 2.90 (s, 3H), 2.89
(s, 3H), 2.39 (s, 3H), 1.43 (t, J = 7.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3, TMS) δ 149.1, 141.5, 138.6, 137.3,
134.9, 131.7, 131.2, 129.1, 125.1, 124.2, 122.9, 121.1,
119.1, 118.6, 117.4, 114.6, 108.4, 84.6, 60.7, 39.3, 21.5,
20.2, 15.4, 13.0; m/z = 368, positive mode; Anal. Calcd
for C26H25NO: C, 84.98; H, 6.86; N, 3.81%; found: C,
84.85; H, 6.72; N, 3.76%.
2.2d 9-Benzyl-3-(3-(4-methoxyphenyl)prop-2-ynyloxy)-
6-methyl-9H-carbazole (3d): mp: 134–136◦C; IR(KBr):
3020, 2916, 2228, 1600, 1510, 1475, 1355, 1322,
1240, 1222, 1174, 1050, 1026, 908 cm−1; H NMR
1
(400 MHz, CDCl3, TMS) δ 7.92 (s, 1H), 7.77
(s, 1H), 7.43 (d, 2H), 7.42–7.24 (m, 4H), 7.19–7.13
(m, 3H), 6.85 (d, J = 6.8 Hz, 2H), 5.48 (s, 2H), 5.03
(s, 2H), 3.82 (s, 3H), 2.56 (s, 3H); 13C NMR (100 MHz,
CDCl3, TMS) δ 159.8, 151.9, 139.6, 137.4, 136.5,
133.4, 128.7, 128.1, 127.4, 127.3, 126.4, 123.1, 123.0,
120.3, 115.8, 114.6, 113.9, 109.5, 108.7, 105.7, 87.0,
83.2, 58.2, 55.3, 46.7, 21.4; m/z = 418, positive mode;
Anal. Calcd for C29H23NO2: C, 83.43; H, 5.55; N,
3.35%; found: C, 83.28; H, 5.51; N, 3.41%.
2.2h 9-Ethyl-1,4-dimethyl-3-(3-(4-nitrophenyl)prop-
2-ynyloxy)-9H-carbazole (3h): mp: 166–168◦C;
IR(KBr): 2918, 2854, 1743, 1610, 1554, 1508,
1332, 1261, 1205, 1182, 1091, 1016, 883, 869, 812,
1
752 cm−1; H NMR (400 MHz, CDCl3, TMS) δ 8.31
(d, J = 7.2 Hz, 1H), 8.16 (d, J = 7.2 Hz, 2H), 7.60 (d,
J = 7.2 Hz, 2H), 7.57 (t, J = 7.2 Hz, 1H), 7.52 (d, J =
7.2 Hz, 1H), 7.38 (m, 1H), 7.06 (s, 1H), 5.08 (s, 2H),
4.61 (q, J = 7.2 Hz, 2H), 2.86 (s, 3H), 2.84 (s, 3H),
1.43 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3,
TMS) δ 148.7, 141.4, 135.0, 132.5, 132.4, 129.5, 125.2,
123.5, 122.8, 121.0, 120.4, 118.8, 118.7, 117.5, 114.5,
108.5, 90.7, 84.9, 60.4, 39.3, 20.2, 15.5, 13.0; m/z =
326, positive mode; Anal. Calcd for C25H22N2O3: C,
84.89; H, 5.89; N, 4.30%; found: C, 84.51; H, 5.41;
N, 9.93%. m/z = 399, positive mode; Anal. Calcd for
C25H22N2O3: C, 75.36; H, 5.57; N, 7.03%; found: C,
75.48; H, 5.51; N, 7.12%.
2.2e 9-Benzyl-3-methyl-6-(3-p-tolylprop-2-ynyloxy)-
9H-carbazole (3e): mp: 128–130◦C; IR(KBr): 3026,
2915, 2227, 1601, 1491, 1475, 1356, 1243, 1226, 1171,
1055, 1021, 911 cm−1; H NMR (400 MHz, CDCl3,
1
TMS) δ 7.93 (s, 1H), 7.78 (s, 1H), 7.39 (d, J = 7.6 Hz,
2H), 7.28–7.13 (m, 11H), 5.48 (s, 2H), 5.03 (s, 2H),
2.57 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3,
TMS) δ 151.9, 139.6, 138.7, 137.4, 136.5, 131.8, 129.1,
128.8, 128.2, 127.4, 127.3, 126.4, 123.1, 123.0, 120.4,
119.4, 115.8, 109.5, 108.7, 105.7, 87.2, 83.9, 58.2,
46.7, 21.5, 21.4; Anal. Calcd for C30H25NO: C, 84.98;
H, 6.86; N, 3.81%; found: C, 84.85; H, 6.72; N, 3.76%.
2.3 General procedure for iodocyclization
of aryl-O-propargylated carbazoles
2.2f 9-Benzyl-3-methyl-6-(3-(4-nitrophenyl)prop-
2-ynyloxy)-9H-carbazole (3f): mp: 170–172◦C;
IR(KBr): 2922, 2858, 1732, 1593, 1493, 1452, 1340,
1199, 1026, 850, 796 cm−1; 1H NMR (400 MHz,
CDCl3, TMS) δ 8.16 (d, J = 8.8 Hz, 2H), 7.90 (s,
1H), 7.74 (d, J = 2.0 Hz, 1H), 7.57 (d, J = 8.8 Hz,
2H), 7.28–7.26 (m, 6H), 7.17–7.12 (m, 3H), 5.46 (s,
2H), 5.04 (s, 2H), 2.50 (s, 3H); 13C NMR (100 MHz,
CDCl3, TMS) δ 151.5, 147.3, 139.6, 137.3, 136.6,
132.6, 129.3, 128.8, 128.3, 127.5, 127.5, 126.4, 123.5,
123.2, 122.8, 120.3, 115.6, 109.6, 108.8, 105.7, 90.1,
85.1, 57.9, 46.7, 21.4; m/z = 447, positive mode; Anal.
Calcd for C29H22N2O3: C, 78.01; H, 4.97; N, 6.27%;
found: C, 78.21; H, 5.06; N, 6.35%.
An oven dried 10 mL round bottom flask equipped
with a teflon coated magnetic stirring bar was charged
with aryl-O-propargyl carbazole (0.2 mmol), sodium
bicarbonate (0.4 mmol) and iodine (0.6 mmol) in
nitromethane (2 mL) and reaction mixture was stirred
at room temperature for 4–6 h, after which time TLC
(95:05 hexanes:ethyl acetate) indicated complete con-
version. The reaction mixture was quenched with
5% solution of sodium thiosulphate, extracted with
dichloromethane, dried for an hour sodium sulphate,
adsorbed on silica and purified by column chromatog-
raphy (5–10% ethyl acetate in hexanes) using silica gel
(100–200 mesh).

490
Talluri Krishna Chaitanya and Rajagopal Nagarajan
2.3a 7-Ethyl-2-iodo-1-phenyl-3,7-dihydropyrano[2, NMR (100 MHz, CDCl3, TMS) δ 150.0, 147.6, 146.8,
3-c]carbazole (4a): mp: 146–148◦C; 1H NMR 143.2, 141.5, 136.1, 130.8, 127.5, 126.1, 124.5, 124.5,
(400 MHz, CDCl3, TMS) δ 7.45–7.43 (m, 2H), 7.41 124.1, 123.4, 123.2, 119.3, 117.1, 114.8, 109.1, 91.2,
(d, J = 8.8 Hz, 1H), 7.34–7.23 (m, 6H), 6.60 (m, 40.4, 19.8, 15.1, 12.9; m/z = 525, positive mode; Anal.
1H), 6.56 (d, J = 8.0 Hz, 1H), 6.08 (s, 2H), 4.36 Calcd for C25H21IN2O3: C, 57.26; H, 4.04; N, 5.34%;
(q, J = 7.6 Hz, 2H), 1.43 (t, J = 7.6 Hz, 3H); 13C found: 57.36; H, 4.08; N, 5.23%.
NMR (100 MHz, CDCl3, TMS) δ 150.8, 141.1, 140.4,
140.1, 136.3, 1308, 128.3, 128.0, 124.9, 124.1, 121.9,
119.1, 118.6, 117.8, 114.4, 110.2, 107.8, 86.7, 77.1,
2.4 5-Ethyl-4,10-dimethyl-3-(2-nitro-1-p-tolylvinyl)-
3,5-dihydro-2H-furo[3,2-b]carbazole (5)
37.4, 13.8; m/z = 452, positive mode; Anal. Calcd for
C23H18INO: C, 61.21; H, 4.02; N, 3.10%; found: C,
1
mp: 140–142◦C; H NMR (400 MHz, CDCl3, TMS) δ
61.25; H, 4.04; N, 3.06%.
8.25 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H),
7.42 (d, J = 8.0 Hz, 1H), 7.26–7.19 (m, 5H), 5.93 (d,
J = 5.2 Hz, 1H), 5.50 (m, 1H), 4.84 (dd, J = 9.6 Hz,
2.3b 7-Benzyl-2-iodo-1-(4-nitrophenyl)-3,7-dihydropyrano[2,
3-c]carbazole (4b): mp: 188–190◦C; IR(KBr): 3057,
2922, 2858, 1595, 1514, 1454, 1425, 1194, 1091,
1005, 889, 848, 733 cm−1; 1H NMR (400 MHz, CDCl3,
TMS) δ 8.17 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.8 Hz,
2H), 7.39 (d, J = 8.4 Hz, 1H), 7.30–7.27 (m, 4H),
7.23–7.20 (m, 2H), 7.12 (d, J = 6.8 Hz, 2H), 6.66–
6.63 (m, 2H), 5.52 (s, 2H), 5.10 (s, 2H); 13C NMR
(100 MHz, CDCl3, TMS) δ 151.7, 147.1, 146.9, 141.1,
139.6, 136.9, 136.8, 131.6, 128.9, 127.6, 126.3, 125.6,
123.3, 123.1, 121.4, 118.5, 118.3, 118.0, 114.7, 111.5,
108.7, 88.8, 77.2, 46.5; m/z = 559, positive mode;
Anal. Calcd for C28H19IN2O3: C, 60.23; H, 3.43; N,
5.02%; found: C, 60.45; H, 3.38; N, 5.12%.
J = 9.6 Hz, 1H), 4.54 (dd, J = 3.6 Hz, J = 3.6 Hz,
1H), 4.46 (q, J = 7.6 Hz, 2H), 2.76 (s, 3H), 2.42 (s,
3H), 2.21 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3, TMS) δ 144.6, 142.9, 141.8, 138.7,
137.5, 136.6, 129.4, 126.9, 125.8, 124.2, 123.2, 122.3,
119.8, 119.1, 118.4, 115.9, 108.9, 76.7, 75.6, 70.8, 40.3,
21.2, 20.3, 15.0, 12.7; m/z = 559, positive mode; Anal.
Calcd for C27H26N2O3: C, 76.03; H, 6.14; N, 6.57%;
found: C, 76.31; H, 6.41; N, 6.53%.
3. Results and discussion
In continuation of our efforts in the synthesis of various
heteroarylcarbazole derivatives from easily accessi-
ble precursors,8 we report here, a simple synthesis
of new pyranocarbazole derivatives employing iodocy-
clization. The synthesis of aryl-O-propargylated
precursors is demonstrated in scheme 1. Hydroxycar-
bazoles (1a–1d) were synthesized employing methods
reported in literature.9 These hydroxycarbazoles were
O-alkylated using propargyl bromide, K2CO3 in ace-
tone. The O-propargyl derivatives 2a–d were subjected
to Sonogashira coupling with various aryl iodides
employing Pd(PPh3)2Cl2, CuI and triethylamine as
base in THF (scheme 1). The products 3a–g and their
yields are summarized in table 1. All the products were
obtained in good yields.
Then we carried out the cyclization reaction of
phenyl-O-propargylated derivative 3a in various sol-
vents like THF, dioxane, DMF, etc. We found that the
conditions using nitromethane as solvent, 3 eq. iodine
and 2 eq. sodium bicarbonate gave the best yields.
Employing these optimized conditions, we success-
fully synthesized various pyranocarbazole derivatives
in good yields. The results are summarized in table 2.
Substituents on the aryl ring have significant effect
on the course of reaction. Electron withdrawing sub-
stituents on the aryl group increased the yields. Electron
2.3c 7-Benzyl-2-iodo-10-methyl-1-(4-nitrophenyl)-
3,7-dihydropyrano[2,3-c]carbazole (4c): mp: 194–
196◦C; IR(KBr): 3207, 3069, 3032, 2916, 2852, 1730,
1595, 1518, 1452, 1305, 1211, 1147, 1066, 1014, 848,
1
800, 721 cm−1; H NMR (400 MHz, CDCl3, TMS) δ
8.18 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H),
7.37–7.02 (m, 9H), 6.35 (s, 1H), 5.47 (s, 2H), 5.09 (s,
2H), 2.06 (s, 3H); 13C NMR (100 MHz, CDCl3, TMS)
δ 151.0, 147.2, 147.1, 139.6, 139.4, 137.2, 137.0,
131.9, 128.9, 127.6, 127.6, 127.1, 126.3, 123.2, 123.1,
122.5, 121.5, 118.0, 114.6, 111.4, 108.3, 88.7, 76.0,
46.5, 20.8; m/z = 573, positive mode; Anal. Calcd for
C29H21IN2O3: C, 60.85; H, 3.70; N, 4.89%; found: C,
60.75; H, 3.75; N, 4.76%.
2.3d 6-Ethyl-3-iodo-5,11-dimethyl-4-(4-nitrophenyl)-
2,6-dihydropyrano[3,2-b]carbazole (4d): mp: 180–
182◦C; IR(KBr): 3414, 2961, 2914, 2843, 1595, 1510,
1
1454, 1346, 1176, 1078, 1006, 860, 736 cm−1; H
NMR (400 MHz, CDCl3, TMS) δ 8.26–8.24 (m, 3H),
7.50–7.48 (m, 3H), 7.38 (m, 1H), 7.23 (t, J = 7.2 Hz,
1H), 4.99 (s, 2H), 4.35 (d, J = 6.4 Hz, 2H), 2.80
(s, 3H), 2.02 (s, 3H), 1.28 (d, J = 6.4 Hz, 3H); 13C

Pyranocarbazole derivatives
491
1
All the products were well-characterized by H and
1
13C NMR spectra. Interestingly in the H NMR spec-
tra of cyclized products 4a–c, the C5-H was shifted to
upfield from δ 8.11 (3a) to δ 6.56 (4a). This consider-
able upfield shift can be explained by the anisotropic
effect of the aryl group, which clouds the C5-H after
cyclization (figure 2). The same was observed in the
cases of 4b and 4c. The perpendicular geometry and
proximity of aryl ring can be seen in the crystal struc-
tures of 4a and 4b (figure 3). To our surprise, when
we carried out the reaction with 9-ethyl-1,4-dimethyl-
3-(3-(4-p-Tolyl-prop-2-ynyloxy)-9H-carbazole 3g, we
obtained a completely different product 5 in 70% yield
(scheme 2). A furocarbazole derivative formation is
observed. Formation of a five-membered ring followed
by the replacement of iodine by nitromethyl anion
resulted in the furocarbazole derivative. The proposed
mechanism for this observation is shown in scheme 3.
The compounds 4a and 4b were also character-
ized by X-ray crystallographic analysis.10 The ORTEP
diagrams are shown in figure 3.
Scheme 1. Synthesis of aryl-O-propargylated carbazoles.
donating substituents resulted in a complex mixture
of products. Various substituted carbazoles were em-
ployed, the 1,4-dimethyl derivative 3h provided linear
product, which is of particular interest in biological
applications.
Table 1. Aryl-O-propargylated carbazoles.
Entry
Reactant
Hydroxycarb.
Coupled product
Time (h)
8
Yield (%)
85
1
C6H5I
1b
2
3
4
5
6
4-Me-C6H4I
4-O2N-C6H4I
4-MeO-C6H4I
4-Me-C6H4I
4-O2N-C6H4I
1c
1c
1d
1d
1d
8
8
6
6
6
82
81
85
86
84
7
8
4-Me-C6H4I
1a
8
78
4-O2N-C6H4I
1a
6
85
In all the cases, Pd(PPh3)2Cl2 (2 mol%) and CuI (1 mol%) were used in the presence of Et3N as a base and THF as a solvent
at r.t.

492
Talluri Krishna Chaitanya and Rajagopal Nagarajan
Table 2. Pyranocarbazole derivatives.
Entry
1
Reactant
Cyclized product
Time (h)
4
Yield (%)
70
3a
2
3c
6
72
3
4
3f
6
4
74
78
3h
In all the cases, iodine (3 eq) and NaHCO3 (2 eq) were used in the presence of
nitromethane as solvent at r.t.
I
X
H
R2
O
C5
N
R
Figure 2. Observation of anisotropic effect in 4a–c.
Scheme 2. Furocarbazole formation.
4a
4b
Figure 3. ORTEP diagrams of 4a and 4b. Hydrogen atoms are omitted for clarity.

Pyranocarbazole derivatives
493
1999 Synlett 596; (i) Knölker H-J, Baum E and Reddy
K R 2000 Tetrahedron Lett. 41 1171; (j) Czerwonka R,
Reddy K R, Baum E and Knölker H-J 2006 Chem. Com-
mun. 711; (k) Fröhner W, Reddy K R and Knölker H-J
2007 Heterocycles 74 895; (l) Mal D, Senapati B K and
Pahari P 2007 Tetrahedron 63 3768; (m) Jana A and Mal
D 2010 Chem. Commun. 46 4411
3. (a) Ito C, Katsuno S, Ruangrungsi N and Furukawa H
1998 Chem. Pharm. Bull. 46 344; (b) Ito C, Katsuno
S, Itoigawa M, Ruangrungsi N, Mukainaka T, Okuda
M, Kitagawa Y, Tokuda H, Nishino H and Furukawa H
2000 J. Nat. Prod. 63 125; (c) Ito C, Itoigawa M, Sato
A, Hasan C M, Rashid M A, Tokuda H, Mukainaka T,
Nishino H and Furukawa H 2004 J. Nat. Prod. 67 1488
4. (a) Oliveira M M and Salvador M A 2005 Mol. Cryst.
Liq. Cryst. 43 173; (b) Delbaere S, Berthet J, Salvador
M A, Vermeersch G and Oliveira M M 2006 Int. J.
Photoenergy 1.
Scheme 3. Proposed mechanism for the formation of 5.
4. Conclusion
5. (a) Larock R C Acetylene Chemistry Chemistry Biol-
ogy and Material Science; Diederich F, Stang P J and
Tykwinski R R Eds.; Wiley-VCH: New York 2005;
Chapter 2 pp 51; (b) Barluenga J, Gonzalez J M, Campos
P J and Asensio G 1988 Angew. Chem., Int. Ed. Engl. 27
1546; (c) Knight D W, Redfern A L and Gilmore J 2002
J. Chem. Soc., Perkin Trans. 1 622; (d) Arcadi A, Cac-
chi S, Fabrizi G, Marinelli F and Moro L 1999 Synlett.
1432; (e) Fischer D, Tomeba H, Pahadi N K, Patil N T
and Yamamoto Y 2007 Angew. Chem., Int. Ed. 46 4764;
(f) Nishizawa M, Takao H, Yadav V K, Imagava H
and Sugihara T 2003 Org. Lett. 5 4563; (g) Manarin
F, Roehrs J A, Gay R M, Brandão R, Menezes P H,
Nogueira C W and Zeni G 2009 J. Org. Chem. 74 2153;
(h) Laya S M, Banerjee A K and Cabrera E V 2009 Curr.
Org. Chem. 13 720
6. (a) Knight D W, Redfern A L and Gilmore J 1998 Chem.
Commun. 2207; (b) Arcadi A, Cacchi S, Giuseppe S D,
Fabrizi G and Marinelli F 2002 Org. Lett. 4 2409;
(c) Barluenga J, Vazque-Villa H, Ballesteros A and
Gonzalez J M 2003 J. Am. Chem. Soc. 125 9028; (d)
Yue D, Yao T and Larock R C 2005 J. Org. Chem. 70
10292; (e) Yue D, Yao T and Larock R C 2005 J. Com.
Chem. 7 809; (f) Yao T, Zhang X and Larock R C 2005
J. Org. Chem. 70 7679; (g) Yao T, Zhang X and Larock
R C 2004 J. Am. Chem. Soc. 126 11164; (h) Larock
R C and Yue D 2001 Tetrahedron Lett. 42 6011;
(i) Zhang X, Campo M A, Yao T and Larock R C 2005
Org. Lett. 7 763; (j) Zhang X, Sarkar S and Larock R C
2006 J. Org. Chem. 71 236; (k) Waldo J P and Larock
R C 2005 Org. Lett. 7 5203; (l) Waldo J P and Larock
R C 2007 J. Org. Chem. 72 9643; (m) Barluenga J,
Trincado M, Marco-Arias M, Ballesteros A, Rubio E
and Gonzalez J M 2005 Chem. Commun. 2008
In conclusion, we report here a simple and facile syn-
thesis of new pyranocarbazole derivatives from eas-
ily accessible O-propargylated carbazoles employing
iodocyclization in good yields. An interesting prod-
uct with nitromethane insertion is observed. Further
investigations are under progress.
Acknowledgements
We gratefully acknowledge the Department of Sci-
ence and Technology (DST) for financial assistance
(Project number: SR/S1/OC-70/2008) and for provid-
ing a single-crystal X-ray diffractometer facility in our
school. TKC thanks Council of Scientific and Indus-
trial Research (CSIR) for Senior Research Fellowship.
The authors thank Mr. Bharat, Mr. Anand and Mr.
Nagarjuna for their help in solving crystal structures.
References
1. (a) Gribble G W The Alkaloids; Brossi A Ed.; Academic
Press: San Diego CA, 1990 p 239; (b) Knölker H-J and
Reddy K R 2002 Chem. Rev. 102 4303; (c) Cordell G A
The Alkaloids; 2008 vol. 65; (d) Gribble G W 1991 Syn-
lett. 28 289; (e) Gribble G W, Saulnier M G, Sibi M P
and Obaza-Nutaitis J A 1984 J. Org. Chem. 49 4518; (f)
Knölker H-J The Alkaloids, (G A Cordell ed.) Academic
Press Amsterdam 2008 65 1–430; (g) Kirsch G H 2001
Curr. Org. Chem. 5 507
7. (a) Kesharwani T, Worlikar S A and Larock R C 2006 J.
Org. Chem. 71 2307; (b) Zhang X, Yao T, Campo M A
and Larock R C 2010 Tetrahedron 66 1177; (c) Mehta S,
Waldo J P and Larock R C 2009 J. Org. Chem. 74 1141
8. (a) Gaddam V, Ramesh S and Nagarajan R 2010 Tetra-
hedron 66 4218; (b) Gaddam V and Nagarajan R 2007
J. Org. Chem. 72 3573; (c) Gaddam V and Nagarajan
R 2008 Org. Lett. 10 1975; (d) Chaitanya T K and
Nagarajan R 2007 Tetrahedron Lett. 48 2489; (e)
Meesala R and Nagarajan R 2010 Tetrahedron Lett.
2. (a) Naffziger M R, Ashburn B O, Perkins J R and Carter
R G 2007 J. Org. Chem. 72 9857; (b) Lebold T P
and Kerr M A 2008 Org. Lett. 10 997; (c) Lebold T
P and Kerr M A 2007 Org. Lett. 9 1883; (d) Forke R,
Krahl M P, Krause T, Schlechtingen G and Knölker H-
J 2007 Synlett. 268; (e) Krahl M P, Jager A, Krause T
and Knölker H-J 2006 Org. Biomol. Chem. 4 3215; (f)
Knölker H-J and Wolfgang F 1997 Synlett. 1108; (g)
Knölker H-J, Fröhner W and Wagner A 1998 Tetrahe-
dron Lett. 39 2947; (h) Knölker H-J and Reddy K R

494
Talluri Krishna Chaitanya and Rajagopal Nagarajan
51 422; (f) Jella R R and Nagarajan R 2011 Synlett. 10. (a) The CCDC deposition number of 4a is 818251;
529
molecular formula: C23H18INO, unit cell parameters: a
6.4622(14) b 13.492(3) c 21.416(5) beta 98.668(3) space
group P21/c; (b) The CCDC deposition number of 4b
is 818250; molecular formula: C28H19IN2O3, unit cell
parameters: a 17.9078(18) b 12.4689(15) c 20.656(2)
space group Pna21
9. Tran-Thi H A, Nguyen-Thi T, Michel S, Tillequin F,
Koch M, Pfeiffer B, Pierre A and Trinh-Van-Dufat H
2004 Chem. Pharm. Bull. 52 540; (b) Langendoen A,
Koomen G-J and Pandit U K 1987 Heterocycles 26
91