Synthesis of biogenetically possible 3-substituted pyrano-[2,3-a]carbazoles

Article abstract of DOI:10.3184/030823409X12523375431104

3-Substituted pyrano[2,3-a]carbazol-2(11H)-ones have been synthesised by the reaction of 1-hydroxy-carbazole-2- carbaldehyde with malononitrile, ethyl cyanoacetate, Meldrum's acid, (carbethoxymethylene)triphenylphosphorane, ethyl benzoylacetate and phenylacetonitrile.

Full text of DOI:10.3184/030823409X12523375431104

JOURNAL OF CHEMICAL RESEARCH 2009
OCTOBER, 619–622
RESEARCH PAPER 619
Synthesis of biogenetically possible 3-substituted pyrano-
[2,3-a]carbazoles
Kumaresan Prabakaran and Karnam Jayaramapillai Rajendra Prasad*
Department of Chemistry, Bharathiar University, Coimbatore, Tamil Nadu, India
3-Substituted pyrano[2,3-a]carbazol-2(11H)-ones have been synthesised by the reaction of 1-hydroxy-carbazole-2-
carbaldehyde with malononitrile, ethyl cyanoacetate, Meldrum's acid, (carbethoxymethylene)triphenylphosphorane,
ethyl benzoylacetate and phenylacetonitrile.
Keywords: carbazoles, fused carbazoles, pyrans, Wittig reactions, Meldrum's acid
Carbazole alkaloids isolated from taxonomically related higher
plants of the genus Murraya, Glycosmis and Clausena which
belong to the Rutaceae family1-4 have been reported to show
antitumor, antibiotic, antimalarial and antifungal properties.5
Many of these compounds have oxygenated functionality in
the 1- or 2-position and possess cytotoxic activity.5,6
Recently we have reported the synthesis of some substituted
pyranocarbazoles.15,17-20 In continuation of this work, we
report here some new 3-substituted pyrano[2,3-a]carbazol-
2(11H)-ones prepared by a simple synthetic pathway.
Results and discussion
Girinimbine was the first isolated pyrano[3,2-a]carbazole
alkaloid.7,8 Later, several other pyranocarbazoles were
isolated and synthesised due to their important biological
activities.1,9-11 As indicated in an earlier report, it has been
observed that carbazole having an a-pyrone as part of their
structure with [2,3-a] fusion are biogenetically possible as
evident from the naturally available mupamine.12 The naturally
occurring carbazole alkaloids, clauszoline-A13, clauszoline-
B13 and clauszoline-H14 have also the same basic carbazole
skeleton of [2,3-a] fusion with a-pyran ring. Clauszoline-
A and clauszoline-B were the first examples of naturally
occurring 1-oxygenated (equivalent C8) carbazole alkaloids
having a dimethylpyran ring fused with the carbazole nucleus.
Some pyranocarbazol-2-ones have been prepared and used
as intermediates in the synthesis of pyridocarbazole15 and
also to prepare 2,2-dimethyl-2H-pyranocarbazole by use of
a Grignard reagent.16 Based on the interesting features of
these 1-oxygenated carbazole compounds, a simple synthetic
method was felt desirable, with a view to the future isolation
of these biogenetically possible compounds from natural
sources.
To obtain the pyrano[2,3-a]carbazoles, we utilised 1-hydroxy-
carbazole-2-carbaldehyde (1), obtained15 from the easily
accessible 2,3,4,9-tetrahydro-1H-carbazol-1-one through
the intermediate 1-hydroxycarbazole, in different ways, to
effect the synthesis of 3-substituted pyrano[2,3-a]carbazol-2
(11H)-ones.
Then, 1-hydroxycarbazole-2-carbaldehyde (1d) was
reacted with malononitrile under mildly basic conditions
(NH4OAc/ethanol) to yield a single product (Scheme 1).
Its IR spectrum showed bands at 3500–2600 cm-1 and
1718 cm-1 due to (CO)OH and a-pyrone carbonyl groups
respectively. Further, signals at 165.5 ppm and 158.1 ppm in
the 13C NMR were consistent with the presence of lactone
and acid carbonyl carbons. The mass spectrum showed the
molecular ion peak at m/z 279 (M+) as the base peak. All the
spectral and analytical details attest the obtained compound
to be 2-oxo-2H-pyrano[2,3-a]carbazole-3-carboxylic acid
(2d). The yield of the product was only 20%. In order to
improve the yield, alternative reagents were adopted, in which
1-hydroxycarbazole-2-carbaldehyde (1) was reacted with
ethyl cyanoacetate and Meldrum's acid under the same
R1
R1
R1
a
R2
R2
b
R2
CHO
N
H
N
N
H
CO2H
COPh
R3
O
R3
O
H
R3
OH
2
3
O
1
O
c
d
R1
R1
R1
R2
R2
R2
+
N
H
N
H
N
H
Ph
CO2Et
R3
O
R3
O
R3
OH
6
4
5
O
O
1-6 a: R1 = CH3, R2, R3 = H
b: R2= CH3, R1, R3 = H
c: R3 = CH3, R1, R2 = H
d: R1, R2, R3 = H
Reagents and conditions: a: malononitrile, ethyl cyanoacetate, or Meldrum's acid, NH4OAc, EtOH;
b: ethyl benzoylacetate, pyridine, piperidine, reflux; c: phenylacetonitrile, pyridine, piperidine,
reflux; d: Ph3P=CHCO2Et, toluene, 120o
Scheme 1
* Correspondent. E-mail: prasad_125@yahoo.com

620 JOURNAL OF CHEMICAL RESEARCH 2009
tested by TLC with plates coated with silica gel-G with petroleum
ether, ethyl acetate and methanol as developing solvents.
conditions to get the product 2, in moderate (40%) and good
(80%) yields, respectively.
Our next objective was 3-benzoylpyrano[2,3-a]carbazol-
2(11H)-one. 1-Hydroxycarbazole-2-carbaldehyde (1) reacted
with ethyl benzoylacetate in pyridine and piperidine at
reflux temperature to afford a single product. The presences
of an a-pyrone carbonyl peak at 1724 cm-1 and C=O peak
at 1643 cm-1 in its IR spectrum and 13 aromatic protons in
2-Oxo-2H-pyrano[2,3-a]carbazole-3-carboxylic acids (2): general
(optimal) procedure
A mixture of the respective 1-hydroxycarbazole-2-carbaldehyde
(1) (0.5 mmol), Meldrum's acid (86 mg, 0.6 mmol) and ammonium
acetate (154 mg, 2 mmol) in dry ethanol (15 mL) was refluxed
on a steam bath for 2 h. The reaction was monitored by TLC.
After the completion of the reaction the obtained precipitate was
filtered, washed with ethanol and then water to give the respective
2-oxo-2H-pyrano[2,3-a]carbazole-3-carboxylic acid (2) which was
then recrystallised from a large volume of methanol.
8-Methyl-2-oxo-2H-pyrano[2,3-a]carbazole-3-carboxylic acid (2a):
Orange solid (124 mg, 85%), m.p. >300°C. IR: nmax 3500–2600,
3400, 3046, 1736, 1611 cm-1. NMR (DMSO-d6): dH 2.48 (s, 3H,
C8-CH3), 7.31 (d, 1H, C6-H, J = 8.32 Hz), 7.43–7.48 (m, 2H, C9-,
C10-H), 7.99–8.01 (m, 2H, C5-, C7-H), 8.33 (s, 1H, C4-H), 12.00
(b s, 1H, N11-H); dC 21.05 (C8-CH3), 111.4 (C5), 112.0 (C10), 114.
6 (C6a), 117.4 (C3), 118.2 (C6), 120.9 (C9), 122.2 (C7), 122.3 (C4),
122.9 (C4a), 126.3 (C11a), 127.1 (C6b), 128.4 (C8), 139.1 (C11b),
140.5 (C10a), 158.0 (C2), 165.4 (COOH). MS: m/z (%) 293(M+, 58),
276 (100), 248 (8), 220 (15), 195 (22), 179 (65), 155 (15), 90 (5), 60
(12), 43 (58). Anal. Calcd for C17H11NO4: C, 69.62; H, 3.78; N, 4.78.
Found: C, 69.48; H, 3.82; N, 4.22%.
9-Methyl-2-oxo-2H-pyrano[2,3-a]carbazole-3-carboxylic acid (2b):
Yellow solid (117 mg, 80%), m.p. >300°C. IR: nmax 3500–2600,
3402, 3022, 1739, 1607 cm-1. NMR (DMSO-d6): dH 2.50 (s. 3H,
C9-CH3), 7.08 (d, 1H, C8-H, J = 8.08 Hz), 7.35 (s, 1H, C10-H), 7.56
(d, 1H, C6-H, J = 8.20 Hz), 8.05 (d, 1H, C5-H, J = 8.20 Hz), 8.08 (d,
1H, C7-H, J = 8.08 Hz), 8.88 (s, 1H, C4-H), 12.15 (b s, 1H, N11-H);
dC 21.45 (C9-CH3), 111.7 (C10), 112.1 (C5), 114. 5 (C6a), 117.25
(C3), 118.5 (C6), 120.8 (C7), 121.1 (C6b), 122.0 (C8), 122.2 (C4),
122.9 (C4a), 126.2 (C11a), 129.3 (C9), 139.4 (C11b), 140.5 (C10a),
158.9 (C2), 165.0 (COOH). MS: m/z (%) 293(M+, 70), 276 (100),
247 (16), 220 (8), 194 (12), 167 (38), 98 (14), 60 (18), 43 (46). Anal.
Calcd for C17H11NO4: C, 69.62; H, 3.78; N, 4.78. Found: C, 69.65;
H, 3.67; N, 4.35%.
10-Methyl-2-oxo-2H-pyrano[2,3-a]carbazole-3-carboxylic acid
(2c): Orange solid (130 mg, 89%), m.p. >300°C. IR: nmax 3500–
2600, 3270, 3016, 1735, 1629 cm-1. NMR (DMSO-d6): dH 2.49 (s,
3H, C10-CH3), 7.17 (t, 1H, C8-H, J = 7.50 Hz), 7.31 (d, 1H, C9-H,
J = 7.45), 7.61 (d, 1H, C6-H, J = 8.2 Hz), 8.05 (d, 1H, C7-H,
J = 7.45 Hz), 8.11 (d, 1H, C5-H, J = 8.16 Hz), 8.92 (s, 1H, C4-H),
12.14 (b s, 1H, N11-H), 13.11 (s, 1H, C3-COOH, D2O exchangeable);
dC 16.8 (C10-CH3), 111.7 (C5), 115.1 (C6a), 117.6 (C3), 118.3 (C6),
118.5 (C7), 120.6 (C9), 120.9 (C8), 121.95 (C4), 122.0 (C10), 123.0
(C4a), 126.5 (C11a), 127.0 (C10a), 127.8 (C6b), 140.6 (C11b), 158.5
(C2), 165.0 (COOH). MS: m/z (%) 293(M+, 65), 276 (100), 248 (30),
235 (6), 220 (13), 192 (16), 165 (7), 123 (6), 96 (9), 60 (23), 43 (93).
Anal. Calcd for C17H11NO4: C, 69.62; H, 3.78; N, 4.78. Found: C,
69.53; H, 3.62; N, 4.84%.
1
its H NMR spectrum clearly indicate that the product was
3-benzoylpyrano[2,3-a]carbazol-2(11H)-one 3d (Scheme 1).
3-Phenylpyrano[2,3-a]carbazol-2(11H)-onewassynthesised
by the reaction of 1-hydroxycarbazole-2-carbaldehyde (1)
with phenylacetonitrile in pyridine and piperidine, which
yielded a single product. Its IR spectrum showed absorption
at 1699 cm-1 due to the presence of a-pyrone carbonyl group
and its proton NMR spectrum showed the presence of 13
aromatic protons. Its mass spectrum showed the molecular
ion peak at m/z 311 (M+) as the base peak. All the spectral
and analytical details confirm the obtained compound to be 3-
phenylpyrano[2,3-a]carbazol-2(11H)-one (4d) (Scheme 1).
Much interest centres around the simple pyrano[2,3-a]
carbazol-2(11H)-one structure, because these are suitable
stable intermediates for the synthesis of the biogenetically
possible
2,2-dimethyl-2H-pyrano[2,3-a]carbazoles
by
Grignard reaction and pyrido[2,3-a]carbazoles by treatment
with ammonium acetate. The synthesis of unsubstituted
pyrano[2,3-a]carbazol-2(11H)-one was achieved utilising
Wittig reaction conditions in which 1-hydroxycarbazole-2-
carbaldehyde(1)reactedwith(carbethoxymethylene)triphenyl-
phosphorane to afford two products, which were separated by
column chromatography on silica gel, eluting with petroleum
ether/ethyl acetate (98:2 and 95:5) (Scheme 1). The product
obtained from the first fraction was found to be similar to
the known15 compound pyrano[2,3-a]carbazol-2(11H)-one
(5d), with superimposible IR spectra. The IR spectrum of the
second product showed absorption at 1653 cm-1 and its proton
NMR spectrum exhibited two doublets with J = 15.84 Hz
corresponding to olefinic trans protons. A two proton quartet
at d 3.34 ppm and a three proton triplet at d 1.39 ppm with
J = 7.12 Hz indicate the presence of an ethyl ester group.
Its molecular ion peak appeared at m/z 281. All the spectral
and analytical details revealed that the product obtained
was ethyl (E)-b-(1-hydroxy-9H-carbazol-2-yl)acrylate (6d).
Mechanistically, it can be supposed that the reaction of
1-hydroxycarbazole-2-carbaldehyde (1) with (carbethoxy-
methylene)triphenylphosphorane yielded both E- and Z-
isomers, themorereactiveZisomerinsituaffordingthepyrano-
[2,3-a]carbazol-2(11H)-one (5) on intramolecular cyclisation.
In conclusion, some 3-substituted pyrano[2,3-a]carbazol-
2(11H)-ones have been synthesised using a simple pathway.
These heterocyclic analogues are suitable stable intermediates
to the synthesis of biogenetically possible 2,2-dimethyl-
2H-pyrano[2,3-a]carbazoles and pyrido[2,3-a]carbazoles
and may possess important applications in the preparation
of biologically active natural products as well as in
pharmaceuticals.
2-Oxo-2H-pyrano[2,3-a]carbazole-3-carboxylic acid (2d): Yellow
solid (124 mg, 88%), m.p. >300°C. IR: nmax 3500–2700, 3400, 1718,
1639, 1609cm-1. NMR(DMSO-d6):dH 7.21(t, 1H, C9-H, J=7.44Hz),
7.42–7.47 (m, 2H, C8-, C10-H), 7.53 (d, 1H, C6-H, J = 8.15 Hz),
8.02 (d, 1H, C5-H, J = 8.10 Hz), 8.17 (d, 1H, C7-H, J = 7.84 Hz),
8.24 (s, 1H, C4-H), 12.12 (b s, 1H, N11-H); dC 111.7 (C5), 115.4
(C6a), 116. 1 (C10), 117.2 (C3), 118.4 (C6), 119.4 (C8), 120.7 (C7),
122.1 (C4), 122.8 (C4a), 125.6 (C6b), 126.2 (C11a), 126.6 (C9),
140.7 (C11b), 142.4 (C10a), 158.1 (C2), 165.5 (COOH). MS: m/z
(%) 279(M+, 90), 262 (100), 235 (57), 207 (60), 178 (76), 152 (53),
139 (19), 125 (15), 103 (23), 89 (38), 76 (52), 63 (25), 45 (49). Anal.
Calcd for C16H9NO4: C, 68.82; H, 3.25; N, 5.02. Found: C, 68.66; H,
3.28; N, 4.96%.
Experimental
3-Benzoylpyrano[2,3-a]carbazol-2(11H)-ones (3): general procedure
To a hot solution of the 1-hydroxycarbazole-2-carbaldehyde (1)
(0.5 mmol) and ethyl benzoylacetate (0.192 g, 1 mmol) in pyridine
(5 mL) was added 4 drops of piperidine. Then the temperature was
raised to reflux and maintained for 6 h. The reaction was monitored
by TLC. After completion of reaction the excess solvent was removed
and the reaction mixture was poured into ice-water and neutralised
with 5N HCl. The solid was filtered, dried and purified by column
chromatography over silica gel using chloroform/methanol (95:5) as
eluant to get the respective 3-benzoylpyrano[2,3-a]carbazol-2(11H)-
ones (3). The compound thus obtained was recrystallised from
ethanol.
Melting points were determined on a Mettler FP 51apparatus (Mettler
Instruments, Switzerland). IR spectra were recorded on a Shimadzu
FTIR-8201PC spectrophotometer (Shimadzu, Japan) using KBr
discs. 1H NMR and 13C NMR spectra were recorded on a Bruker
AMX 400 spectrometer, and also a Bruker AMX 500 spectrometer;
the chemical shifts are expressed in parts per million (ppm) from
tetramethylsilane (TMS) as internal reference. Mass spectra (MS)
were recorded on AutoSpec EI and Shimadzu QP 2010 PLUS GC-
MS mass spectrometers. Microanalyses were performed on a Vario
EL III model CHNS analyser (Vario, Germany) at the Department
of Chemistry, Bharathiar University. The purity of the products was

JOURNAL OF CHEMICAL RESEARCH 2009 621
3-Benzoyl-8-methyl-pyrano[2,3-a]carbazol-2(11H)-one
(3a):
127.2 (C6b), 128.0 (C4'), 128.5 (C8), 128.6 (C3', C5'), 128.8 (C2',
C6'), 130.3 (C11a) 132.9 (C11b), 134.5 (C1'), 140.6 (C10a), 141.1
(C4), 160.4 (C2). MS: m/z (%) 325 (M+, 100), 298 (12), 297 (72),
296 (40), 267 (26), 254 (13), 239 (5), 163 (8), 149 (29), 134 (32), 120
(10), 77 (8). Anal. Calcd for C22H15NO2: C, 81.21; H, 4.65; N, 4.30.
Found: C, 81.28; H, 4.67; N, 4.40%.
9-Methyl-3-phenylpyrano[2,3-a]carbazol-2(11H)-one (4b):Yellow
solid (76 mg, 47%), m.p. 280°C. IR: nmax 3323, 2923, 1696, 1624,
1599 cm-1. NMR (CDCl3): dH 2.51 (s, 3H, C9-CH3), 7.05 (d, 1H, C8-
H, J = 8.0 Hz), 7.33 (d, 1H, C6-H, J = 8.3 Hz), 7.40 (s, 1H, C10-H),
7.47–7.50 (m, 3H, C3'-, C4'-, C5'-H), 7.76–7.78 (m, 2H, C2'-, C6'-H),
7.95 (d, 1H, C5-H, J = 8.3 Hz), 8.00 (d, 1H, C7-H, J = 8.00 Hz),
8.03 (s, 1H, C4-H), 8.72 (b s, 1H, N11-H); dC 21.5 (C9-CH3), 110.3
(C6a), 112.2 (C5), 112.9 (C10), 117.1 (C6), 118.6 (C4a), 120.3
(C6b), 120.7 (C7), 121.7 (C8), 124.6 (C3), 127.8 (C4'), 128.6 (C3',
C5'), 128.9 (C2', C6'), 130.7 (C11a) 132.0 (C9), 133.7 (C11b), 134.9
(C1'), 141.0 (C4), 142.1 (C10a), 160.3 (C2). MS: m/z (%) 325 (M+,
100), 297 (46), 296 (38), 267 (17), 248 (13), 239 (8), 163 (21), 134
(27), 120 (7), 77 (5). Anal. Calcd for C22H15NO2: C, 81.21; H, 4.65;
N, 4.30. Found: C, 81.14; H, 4.69; N, 4.37%.
10-Methyl-3-phenylpyrano[2,3-a]carbazol-2(11H)-one (4c): Yellow
solid (82 mg, 51%), m.p. 271°C. IR: nmax 3350, 3045, 1689,
1610 cm-1. NMR (CDCl3): dH 2.63 (s, 3H, C10-CH3), 7.25 (t, 1H,
C8-H, J = 8.0 Hz), 7.34 (d, 1H, C6-H, J = 8.0 Hz), 7.36 (d, 1H,
C9-H, J = 7.92 Hz), 7.44 (t, 1H, C4'-H, J = 7.40 Hz), 7.48–7.51 (m,
2H, C3'-, C5'-H), 7.77–7.80 (m, 2H, C2'-, C6'-H), 7.96 (d, 1H, C5-H,
J = 8.0 Hz), 7.97 (d, 1H, C7-H, J = 8.00 Hz), 8.03 (s, 1H, C4-H),
8.75 (b s, 1H, N11-H); dC 16.8 (C10-CH3), 110.3 (C6a), 112.3 (C6),
112.4 (C5), 118.4 (C7), 118.7 (C4a), 120.7 (C9), 120.9 (C8), 122.3
(C10), 124.8 (C3), 127.7 (C10), 127.8 (C4'), 128.0 (C6b), 128.6 (C3',
C5'), 128.9 (C2', C6'), 130.7 (C11a) 133.2 (C11b), 134.9 (C1'), 141.2
(C4), 160.5 (C2). MS: m/z (%) 325 (M+, 100), 297 (41), 296 (62),
267 (11), 254 (8), 248 (21), 220 (8), 163 (21), 153 (27), 129 (9), 77
(9). Anal. Calcd for C22H15NO2: C, 81.21; H, 4.65; N, 4.30. Found:
C, 81.41; H, 4.72; N, 4.32%.
3-Phenylpyrano[2,3-a]carbazol-2(11H)-one (4d): Yellow solid
(82 mg, 53%), m.p. 289°C. IR: nmax 3307, 1699, 1633, 1607 cm-1.
NMR (CDCl3): dH 7.33 (t, 1H, C8-H, J = 7.5 Hz), 7.38 (d, 1H, C6-
H, J = 8.0 Hz), 7.44 (t, 1H, C4'-H, J = 7.40 Hz), 7.48–7.55 (m, 3H,
C9-, C3'-, C5'-H), 7.58 (d, 1H, C10-H, J = 8.0 Hz), 7.77–7.79 (m,
2H, C2'-, C6'-H), 7.98 (d, 1H, C5-H, J = 8.0 Hz), 8.04 (s, 1H, C4-
H), 8.13 (d, 1H, C7-H, J = 8.0 Hz), 8.88 (b s, 1H, N11-H); dC 110.4
(C6a), 112.4 (C5), 116.1 (C10), 116.4 (C6), 118.5 (C4a), 119.8 (C9),
120.7 (C7), 124.7 (C3),125.6 (C6b), 126.0 (C8), 127.9 (C4'), 128.7
(C3', C5'), 128.9 (C2', C6'), 130.6 (C11a) 132.5 (C11b), 134.4 (C1'),
141.2 (C4), 142.3 (C10a), 160.75 (C2). MS: m/z (%) 311 (M+, 100),
285 (54), 261 (17), 235 (38), 234 (15), 220 (12), 206 (8), 165 (6), 143
(8), 115 (9), 77 (16). Anal. Calcd for C21H13NO2: C, 81.01; H, 4.21;
N, 4.50. Found: C, 81.10; H, 4.18; N, 4.38%.
Yellow solid (113 mg, 64%), m.p. 303°C. IR: nmax 3312, 2935, 1717,
1654, 1631 cm-1. NMR (DMSO-d6): dH 2.51 (s, 3H, C8-CH3), 7.34
(d, 1H, C9-H, J = 7.8 Hz), 7.48 (d, 1H, C6-H, J = 8.32 Hz), 7.53–
7.56 (m, 3H, C10-, C3'-, C5'-H), 7.69 (t, 1H, C4'-H, J = 7.4 Hz),
7.93–7.95 (m, 2H, C2'-, C6'-H), 8.02 (s, 1H, C7-H), 8.10 (d, 1H, C5-
H, J = 8.12 Hz), 8.58 (s, 1H, C4-H), 12.17 (b s, 1H, N11-H); dC 21.0
(C8-CH3), 109.4 (C6a), 111.7 (C10), 114.4 (C5), 116.8 (C6), 119.05
(C4a), 120.6 (C9), 122.1 (C7), 123.65 (C3), 126.4 (C6b), 127.2
(C11a), 128.6 (C2', C6'), 129.0 (C8), 129.4 (C3', C5'), 133.5 (C11b),
136.5 (C4'), 139.5 (C1'), 141.6 (C10a), 147.5 (C4), 158.05 (C2),
192.0 (C=O). MS: m/z (%) 353 (M+, 70), 339 (12), 325 (12), 276
(15), 248 (6), 192 (32), 191 (7), 190 (8), 178 (9), 163 (5), 105 (100),
77 (94), 51 (17). Anal. Calcd for C23H15NO3: C, 78.17; H, 4.28; N,
3.96. Found: C, 78.07; H, 4.32; N, 3.96%.
3-Benzoyl-9-methylpyrano[2,3-a]carbazol-2(11H)-one
(3b):
Yellow solid (102 mg, 58%), m.p. 273°C. IR: nmax 3302, 2949, 1718,
1639. NMR (DMSO-d6): dH 2.51 (s, 3H, C9-CH3), 7.06 (d, 1H, C8-
H, J = 7.5 Hz), 7.39 (s, 1H, C10-H), 7.54–7.61 (m, 3H, C6-, C3'-,
C5'-H), 7.70 (t, 1H, C4'-H, J = 7.5 Hz), 7.95–7.98 (m, 2H, C2'-, C6'-
H), 8.10 (d, 1H, C5-H, J = 8.16 Hz), 8.15 (d, 1H, C7-H, J = 8.0 Hz),
8.62 (s, 1H, C4-H), 12.37 (b s, 1H, N11-H); dC 21.2 (C9-CH3), 109.4
(C6a), 111.1 (C10), 113.4 (C5), 116.7 (C6), 119.3 (C4a), 120.1 (C6b),
120.6 (C7), 121.5 (C8), 123.45 (C3), 127.4 (C11a), 128.6 (C2', C6'),
129.5 (C3', C5'), 130.7 (C9), 132.6 (C11b), 136.4 (C4'), 139.1 (C1'),
140.2 (C10a), 148.0 (C4), 157.9 (C2), 191.9 (C=O). MS: m/z (%)
353 (M+, 55), 339 (8), 338 (5), 325 (17), 276 (9), 248 (4), 192 (43),
190 (6), 163 (7), 105 (100), 77 (61). Anal. Calcd for C23H15NO3: C,
78.17; H, 4.28; N, 3.96. Found: C, 78.21; H, 4.30; N, 4.05%.
3-Benzoyl-10-methylpyrano[2,3-a]carbazol-2(11H)-one
(3c):
Yellow solid (120 mg, 68%), m.p. 248°C. IR: nmax 3253, 2931, 1689,
1626, 1602 cm-1. NMR (DMSO-d6): dH 2.65 (s, 3H, C10-CH3), 7.19
(t, 1H, C8-H, J = 8.0 Hz), 7.33 (d, 1H, C6-H, J = 7.7 Hz), 7.55–7.60
(m, 3H, C9-, C3'-, C5'-H), 7.71 (t, 1H, C4'-H, J = 7.5 Hz), 7.95–7.98
(m, 2H, C2'-, C6'-H), 8.07 (d, 1H, C5-H, J = 7.5 Hz), 8.15 (d, 1H,
C7-H, J = 8.5 Hz), 8.61 (s, 1H, C4-H), 12.17 (b s, 1H, N11-H); dC
16.6 (C10-CH3), 109.3 (C6a), 114.1 (C5), 116.5 (C6), 118.4 (C7),
119.8 (C4a), 120.6 (C9), 120.9 (C8), 122.2 (C10), 123.6 (C3), 127.0
(C11a), 127.7 (C10a), 127.9 (C6b), 128.75 (C2', C6'), 129.4 (C3',
C5'), 133.8 (C11b), 136.6 (C4'), 139.4 (C1'), 147.5 (C4), 158.0 (C2),
191.9 (C=O). MS: m/z (%) 353 (M+, 60), 339 (12), 338 (8), 324 (15),
276 (11), 248 (5), 192 (38), 190 (4), 163 (18), 105 (100), 77 (74).
Anal. Calcd for C23H15NO3: C, 78.17; H, 4.28; N, 3.96. Found: C,
78.28; H, 4.37; N, 3.95%.
3-Benzoylpyrano[2,3-a]carbazol-2(11H)-one (3d): Yellow solid
(113 mg, 67%), m.p. 296°C. IR: nmax 3302, 1724, 1643, 1591 cm-1.
NMR (DMSO-d6): dH 7.27 (t, 1H, C8-H, J = 8.0 Hz), 7.50-7.61 (m,
5H, C6-, C9-, C10-, C3'-, C5'-H), 7.70 (t, 1H, C4'-H, J = 7.5 Hz),
7.95-7.97 (m, 2H, C2'-, C6'-H), 8.16 (d, 1H, C5-H, J = 8.0 Hz),
8.25 (d, 1H, C7-H, J = 8.0 Hz), 8.60 (s, 1H, C4-H), 12.43 (b s, 1H,
N11-H); dC 108.8 (C6a), 114.5 (C5), 116.1 (C10), 116.7 (C6), 119.4
(C8), 119.65 (C4a), 120.85 (C7), 123.4 (C3), 125.6 (C6b), 126.7
(C9), 127.0 (C11a), 129.0 (C2', C6'), 129.5 (C3', C5'), 133.8 (C11b),
136.6 (C4'), 138.8 (C1'), 141.3 (C10a), 148.3 (C4), 158.6 (C2), 191.0
(C=O). MS: m/z (%) 339 (M+, 64), 313 (24), 287 (8), 262 (6), 248
(11), 234 (8), 206 (11), 171 (38), 143 (4), 115 (13), 94 (100), 77 (21).
Anal. Calcd for C22H13NO3: C, 77.87; H, 3.86; N, 4.13. Found: C,
77.89; H, 3.91; N, 4.09%.
Pyrano[2,3-a]carbazol-2(11H)-ones (5) and ethyl (E)-b-(1-hydroxy-
9H-carbazol-2-yl)acrylates (6), general procedure
To a solution of the 1-hydroxycarbazole-2-carbaldehyde (1, 0.5 mmol)
in toluene (10 mL) was added (carbethoxymethylene)triphenyl-
phosphorane (174 mg, 0.5 mmol). The reaction mixture was heated
at 120°C for 6 h. After completion of the reaction the solvent was
removed and the residue was poured into ice-water and extracted with
ethyl acetate. The organic phase was dried ( MgSO4), evaporated and
purified by column chromatography over silica gel using petroleum
ether/ethyl acetate (98:2 and 95:5) as eluant to give the products
pyrano[2,3-a]carbazol-2(11H)-one (5) and ethyl (E)-b-(1-hydroxy-
9H-carbazol-2-yl)acrylate (6) successively.
3-Phenylpyrano[2,3-a]carbazol-2(11H)-ones (4), general procedure
To a hot solution of 1-hydroxycarbazole-2-carbaldehyde (1, 0.5 mmol)
and phenylacetonitrile (0.117 g, 1 mmol) in pyridine (5 mL) was
added piperidine (4 drops). Then the temperature was raised to
reflux and maintained for 6 h. The reaction was monitored by TLC.
After completion of the reaction the excess solvent was removed and
the residue was poured into ice water and neutralised with 5N HCl.
The solid was filtered off, dried, and purified by column
chromatography over silica gel using petroleum ether/ethyl acetate
(98:2) as eluant to isolate the respective 3-phenylpyrano[2,3-a]
carbazol-2(11H)-one (4). The compound thus obtained was
recrystallised from ethanol.
8-Methyl-3-phenylpyrano[2,3-a]carbazol-2(11H)-one (4a):Yellow
solid (83 mg, 51%), m.p. 316°C. IR: nmax 3315, 2917, 1700, 1635,
1603 cm-1. NMR (CDCl3): dH 2.55 (s, 3H, C8-CH3), 7.33 (d, 1H,
C6-H, J = 8.12 Hz), 7.34 (d, 1H, C9-H, J = 8.28 Hz), 7.40–7.49 (m,
4H, C10-, C3'-, C4'-, C5'-H), 7.74–7.77 (m, 2H, C2'-, C6'-H), 7.90 (s,
1H, C7-H), 7.92 (d, 1H, C5-H, J = 8.08 Hz), 8.01 (s, 1H, C4-H), 8.69
(b s, 1H, N11-H); dC 21.0 (C8-CH3), 108.6 (C6a), 112.1 (C10), 112.5
(C5), 117.4 (C6), 118.6 (C4a), 120.7 (C9), 122.7 (C7), 124.1 (C3),
8-Methylpyrano[2,3-a]carbazol-2(11H)-one (5a): Yellow solid
(47 mg, 38%), m.p. 206°C (lit.15 m.p. 205°C).
Ethyl (E)-b-(1-hydroxy-6-methyl-9H-carbazol-2-yl)acrylate (6a):
Yellow solid: (68 mg, 46%), m.p. 222°C. IR: nmax 3406, 3230, 1664,
1610 cm-1. NMR (CDCl3): dH 1.37 (t, 3H, OCH2CH3, J = 7.12 Hz),
2.52 (s, 3H, C6-CH3), 4.31 (q, 2H, OCH2, J = 7.12 Hz), 6.07 (s,
1H, C1-OH), 6.55 (d, 1H, C2'-H, J = 15.8 Hz), 7.29 (d, 1H, C7-H,
J = 7.28 Hz), 7.34 (d, 1H, C3-H, J = 8.28 Hz), 7.36 (d, 1H, C8-H,
J = 7.42 Hz), 7.62 (d, 1H, C4-H, J = 8.24 Hz), 7.82 (s, 1H, C5-H),
8.14 (d, 1H, C1'-H, J = 15.8 Hz), 8.33 (b s, 1H, N9-H); dC 14.1
(OCH2CH3), 21.2 (C6-CH3), 61.65 (OCH2), 111.0 (C8), 111.7 (C4a),
114.2 (C4), 115.4 (C2), 116.0 (C3), 117.0 (C2'), 120.5 (C7), 123.8
(C5), 127.7 (C9a), 128.4 (C4b), 128.7 (C6), 136.4 (C1), 138.2 (C8a),
145.1 (C1'), 160.7 (C3'). MS: m/z (%) 295(M+, 35), 250 (29), 249
(100), 221 (81), 220 (51), 207 (8), 194 (22), 192 (14), 165 (9), 125
(5), 97 (27). Anal. Calcd for C18H17NO3: C, 73.20; H, 5.80; N, 4.78.
Found: C, 73.08; H, 5.69; N, 4.91%.

622 JOURNAL OF CHEMICAL RESEARCH 2009
9-Methylpyrano[2,3-a]carbazol-2(11H)-one (5b): Yellow solid
(44 mg, 35%), m.p. 165°C (lit.15 m.p. 162°C).
The authors thank IISc, Bangalore, IIT, Chennai and IICT,
Hyderabad for NMR and mass spectral data. The authors
acknowledge UGC, New Delhi, India for financial assistance
under grant no. F31-122/2005.
(E)-Ethyl b-(1-hydroxy-7-methyl-9H-carbazol-2-yl)acrylate (6b):
Yellow solid (60 mg, 41%), m.p. 276°C. IR: nmax 3402, 3233, 2939,
1665,1611cm-1.NMR(CDCl3):dH1.39(t,3H,OCH2CH3,J=7.12Hz),
2.51 (s, 3H, C7-CH3), 4.33 (q, 2H, OCH2, J = 7.12 Hz), 6.18 (s,
1H, C1-OH), 6.59 (d, 1H, C2'-H, J = 15.86 Hz), 7.04 (d, 1H, C6-H,
J = 8.18 Hz), 7.34 (d, 1H, C3-H, J = 8.2 Hz), 7.37 (s, 1H, C8-H),
7.62 (d, 1H, C4-H, J = 8.2 Hz), 8.06 (d, 1H, C5-H, J = 8.12 Hz),
8.28 (d, 1H, C1'-H, J = 15.86 Hz), 8.58 (b s, 1H, N9-H); dC 14.5
(OCH2CH3), 21.2 (C7-CH3), 61.5 (OCH2), 111.3 (C8), 114.1 (C4),
115.2 (C2), 116.4 (C3), 116.6 (C4a), 116.8 (C2'), 120.2 (C4b), 120.6
(C5), 121.8 (C6), 127.5 (C9a), 131.6 (C7), 136.9 (C1), 140.9 (C8a),
145.3 (C1'), 160.9 (C3'). MS: m/z (%) 295(M+, 22), 249 (100), 221
(62), 220 (34), 207 (6), 194 (18), 165 (15), 164 (6), 97 (33). Anal.
Calcd for C18H17NO3: C, 73.20; H, 5.80; N, 4.78. Found: C, 73.15;
H, 5.68; N, 4.86%.
Received 11 May 2009; accepted 6 September 2009
Paper 09/0580 doi: 10.3184/030823409X12523375431104
Published online: 8 October 2009
References
1
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H-J. Knolker and K.R. Reddy, Chem. Rev., 2002, 102, 4303.
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10-Methylpyrano[2,3-a]carbazol-2(11H)-one (5c): Yellow solid
3
(50 mg, 40%), m.p. 196°C (lit.15 m.p. 197°C).
Ethyl (E)-b-(1-hydroxy-8-methyl-9H-carbazol-2-yl)acrylate (6c):
Yellow solid (69 mg, 47%), m.p. 208°C. IR: nmax 3401, 3235,
2966, 1660, 1609 cm-1. NMR (CDCl3): dH 1.39 (t, 3H, OCH2CH3,
J = 7.12 Hz), 2.60 (s, 3H, C8-CH3), 4.35 (q, 2H, OCH2, J = 7.12 Hz),
6.66 (d, 1H, C2'-H, J = 15.92 Hz), 7.18 (t, 1H, C6-H, J = 7.6 Hz),
7.26 (d, 1H, C7-H, J = 7.6 Hz), 7.36 (d, 1H, C3-H, J = 8.24 Hz), 7.48
(s, 1H, C1-OH), 7.63 (d, 1H, C4-H, J = 8.2 Hz), 7.89 (d, 1H, C5-H,
J = 7.84 Hz), 8.31 (d, 1H, C1'-H, J = 15.92 Hz), 8.72 (b s, 1H, N9-
H); dC 14.4 (OCH2CH3), 16.85 (C8-CH3), 61.8 (OCH2), 111.6 (C4a),
114.2 (C4), 115.3 (C2), 116.6 (C3), 116.7 (C2'), 118.45 (C5), 120.6
(C7), 120.9 (C6), 122.2 (C8), 127.4 (C9a), 127.9 (C8a), 127.95 (C4b),
136.8 (C1), 145.2(C1'), 160.9 (C3'). MS: m/z (%) 295(M+, 46), 250
(24), 249 (100), 221 (54), 220 (18), 194 (8), 164 (16), 97 (51). Anal.
Calcd for C18H17NO3: C, 73.20; H, 5.80; N, 4.78. Found: C, 73.31;
H, 5.76; N, 4.72%.
4
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R.S. Kapil, The Alkaloids, Vol. 13, ed. R.H.F. Manske, Academic Press,
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Pyrano[2,3-a]carbazol-2(11H)-one (5d): Yellow solid (46 mg,
39%), m.p. 169°C (lit.15 m.p. 169°C).
11 H-J. Knolker, Chem. Lett.,2009, 38, 8.
Ethyl (E)-b-(1-hydroxy-9H-carbazol-2-yl)acrylate (6d): Yellow
solid (61 mg, 44%), m.p. 213°C. IR: nmax 3375, 3275, 1663, 1617
cm-1. NMR (CDCl3): dH 1.39 (t, 3H, OCH2CH3, J = 7.12 Hz), 4.34
(q, 2H, OCH2, J = 7.12 Hz), 6.23 (s, 1H, C1-OH), 6.61 (d, 1H, C2'-
H, J = 15.84 Hz), 7.24 (t, 1H, C6-H, J = 7.9 Hz), 7.35 (d, 1H, C3-
H, J = 8.2 Hz), 7.44-7.48 (m, 2H, C8-, C9-H), 7.66 (d, 1H, C4-H,
J = 8.2 Hz), 8.04 (d, 1H, C5-H, J = 7.92 Hz), 8.22 (d, 1H, C1'-H,
J = 15.84 Hz), 8.54 (b s, 1H, N9-H); dC 14.16 (OCH2CH3), 61.58
(OCH2), 114.68 (C4), 115.17 (C2), 116.08 (C8), 116.28 (C3), 166.44
(C4a), 116.61 (C2'), 119.39 (C6), 120.91 (C5), 125.62 (C4b), 126.00
(C7), 127.58 (C9a), 135. 92 (C1), 141.83 (C10a), 145.09(C1'), 160.54
(C3'). MS: m/z (%) 281(M+, 63), 236 (16), 235 (100), 208 (42), 182
(10), 181 (6), 165 (16), 77 (21). Anal. Calcd for C17H15NO3: C, 72.58;
H, 5.37; N, 4.98. Found: C, 72.35; H, 5.42; N, 4.96%.
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