Regioselectivity in the 1,3-dipolar cycloaddition reactions of nitrile oxides and organic azides with bromocarbazole-1,4-diones

Article abstract of DOI:10.3987/com-06-10882

The effect exerted by the presence of a bromine atom in 2 or 3 position of a carbazole-1,4-dione on the regiocontrol of 1,3-dipolar cycloaddition reactions with nitrile oxides and organic azides was investigated. Comparison with the results obtained with

Full text of DOI:10.3987/com-06-10882

HETEROCYCLES, Vol. 71, No. 1, 2007
27
HETEROCYCLES, Vol. 71, No. 1, 2007, pp. 27 - 38. © The Japan Institute of Heterocyclic Chemistry
Received, 8th September, 2006, Accepted, 17th November, 2006, Published online, 24th November, 2006. COM-06-10882
REGIOSELECTIVITY IN THE 1,3-DIPOLAR CYCLOADDITION
REACTIONS OF NITRILE OXIDES AND ORGANIC AZIDES WITH
BROMOCARBAZOLE-1,4-DIONES
a
a
a
Muriel Compain-Batissou, Jacques Gentili, Nadia Walchshofer, Monique
a
b
a,*
Domard, Bernard Fenet, and Zouhair Bouaziz
a
University of Claude Bernard Lyon 1, ISPB, EA3741, 8 Avenue Rockefeller,
6
9373 Lyon cedex 08, France. E-mail: bouaziz@univ-lyon1.fr
b
University of Claude Bernard Lyon 1, Department of NMR, 69622 Villeurbanne
cedex, France
Abstract – The effect exerted by the presence of a bromine atom in 2 or 3 position
of a carbazole-1,4-dione on the regiocontrol of 1,3-dipolar cycloaddition reactions
with nitrile oxides and organic azides was investigated. Comparison with the
results obtained with 2,3-unsubstituted-carbazole-1,4-dione shows that bromine
substituents on para-carbazolequinones effectively orient the 1,3-dipolar
cycloadditions. The regiochemistry observed may be explained by the orienting
effect of the bromine atom independently of the values of the orbital coefficients.
INTRODUCTION
As part of our investigations on the biological properties of aryl- and heteroaryl-condensed
carbazolequinones, we have recently reported the synthesis of pyrido- and benzo-derivatives by
1
-3
4
Diels-Alder reaction of tricyclic carbazolediones with some azadienes and carbodienes. We have
particularly studied the orienting effect of bromine atom in [4+2] cycloaddition of 2- or
3
-bromocarbazole-1,4-dione with an azadiene. This reaction provided regioselectively the isomer in
which the nitrogen atom of the azadiene was delivered at the brominated carbon of quinone. In
continuation of this work, we planned to synthesize a series of isoxazolo- and triazolocarbazolequinone
derivatives by the 1,3-dipolar cycloaddition reaction of carbazole-1,4-diones with nitrile oxides and
azides respectively, and to investigate the orienting effect of bromine atom in this reaction. To date, few
5
-12
reports dealing with the 1,3-dipolar cycloaddition of quinones with nitrile oxides
and organic
1
3-18
azides
have been reported in the literature and only one has described the regiocontrol effect of

28
HETEROCYCLES, Vol. 71, No. 1, 2007
12
bromine substituent on naphthoquinones in the reaction with nitrile oxides. In this case, only the
regioisomer in which the oxygen atom of nitrile oxide was linked to the brominated carbon of quinone
was obtained.
In this work, we wish to report our results from a related study of the 1,3-dipolar cycloaddition reactions
of unbrominated carbazolequinone (1a) and bromocarbazolequinones (1b) and (1c) towards both nitrile
oxides (2a) and (2b) and organic azides (5a) and (5b).
RESULTS AND DISCUSSION
Quinone (1a) was obtained starting from the commercially available 4-hydroxycarbazole by a
chemoselective N-alkylation followed by oxidation with Frémy’s salt. Bromoquinones (1b) and (1c) were
prepared from the N-alkylated compound respectively by oxidation/bromination or by
1
bromination/oxidation, according to the procedure which we have reported in a previous paper. Nitrile
oxides (2a) and (2b) were synthesized by dehydrogenation of the corresponding aldoximes with sodium
1
9
hypochlorite. Organic azides (5a) and (5b) can be prepared from the corresponding bromide or chloride
2
0
by reaction with sodium azide in ethanol.
Cycloaddition of carbazolequinones (1a), (1b) and (1c) with nitrile oxides (2a) and (2b):
The reaction of quinone (1a) (Scheme 1) with nitrile oxide (2a) in THF at room temperature affords a
4
8% yield of a mixture of the regioisomeric adducts (3a) and (4a) in approximately equal proportions. In
this case, the primary cycloadducts are not observed, certainly due to a rapid oxidation with 1a. The
reaction with nitrile oxide (2b) requires the presence of basic Al to give a 1:1 mixture of the
2 3
O
regioisomeric compounds (3b) and (4b) in 50% overall yield. In absence of basic Al
leads to a mixture of 3b and 4b plus the corresponding primary cycloadducts.
2
O
3
, this reaction
O
O
O
Ar
N +
5
O
N
4
1
8
THF
rt
Ar C N O
9
+
N
N
O
N
Et
Et
Et
Ar
O
O
O
2
a : Ar =
1a
Me
3a (24%)
3b (25%)
4
a (24%)
N
2
b : Ar =
4b (25%)
Scheme 1. Reaction of carbazolequinone (1a) with nitrile oxides (2a) and (2b).
In order to obtain the regioselective formation of the isoxazolocarbazolequinones (3) and (4), we turn our
attention to the use of the 2- and 3- bromocarbazolequinones (1b) and (1c) in accordance with our study
of the orienting effect of bromine in Diels-Alder cycloadditions (Scheme 2).

HETEROCYCLES, Vol. 71, No. 1, 2007
29
The reaction of 1b with nitrile oxides (2a) and (2b) in THF at room temperature gave selectively 3a and
3
b in 48 and 57% yields, respectively. In similar conditions, 3-bromocarbazolequinone (1c) reacted with
a and 2b to give selectively 4a and 4b in 63 and 35% yields, respectively. The orienting effect of
2
1
2
bromine atom in these reactions agrees with results reported by Behar and co-workers.
O
O
Br
3
2
N
O
N
N
Et
1c
THF, rt
O
Br
O
O
Ar
N
Et
O
O
O
1
b
C
N
THF, rt
N
O
Ar
N
Et
Et
Ar
O
2a
3
a (48%)
4a (63%)
4b (35%)
2
b
3b (57%)
Scheme 2. Reaction of bromocarbazolequinones (1b) and (1c) with nitrile oxides (2a) and (2b).
Concerning the reactive site of quinones in the 1,3-dipolar cycloaddition with nitrile oxides, it has been
6
,7
reported that quinones have two kinds of potentially reactive sites. One is the carbon-oxygen double
bond and the other is the carbon-carbon double bond. In our case, only the C=C cycloaddition reactions
have been observed.
1
Proofs of the regiochemistry were made by H-NMR NOE 1D experiments performed on isomers (3b)
and (4b) (Figure 1). In the case of 3b, an irradiation at 8.12 ppm (H-3’) gives two responses: one on H-4’
(
7.81 ppm) and the other one on H-5 (8.36 ppm). Then, irradiation of the methyl signal at 1.52 ppm
affords two responses: one on the CH of the ethyl group (4.73 ppm) and the other one on H-8 (7.48 ppm).
2
On the other hand, irradiation of the methyl signal (1.47 ppm) of compound (4b) gives four responses:
one on H-6 (7.47 ppm), the second on the CH of the ethyl group (4.70 ppm), the third one on H-3’ (7.88
2
ppm) and the fourth one on the CH -6’ (2.71 ppm).
3
H
4
'
'
CH3
H
O
H
3
1'
H
O
N
9
O
5
10
4
6
1
4
N
8
3
1
O
5
N
3
N
9
1
0
H
N
H
H C
2
O
N
H
1'
H C
CH3
2
O
3'
6
'
CH3
CH3
3
b
4b
1
Figure 1. H-NMR NOE 1D experiments

30
HETEROCYCLES, Vol. 71, No. 1, 2007
Moreover, IR spectra of the regioisomers (3a) and (3b) formed from the 2-bromocarbazolequinone (1b),
show two absorption bands for the carbonyl groups while in the regioisomers (4a) and (4b) formed from
the 3-bromocarbazolequinone (1c), the latter are not differentiated.
In order to better understand the regiochemistry of the [3+2] cycloaddition of quinones (1a), (1b) and (1c)
towards nitrile oxides (2a) and (2b), we used Frontier Molecular Orbital theory and calculations of the
respective LUMO and HOMO energy levels and orbital coefficients were carried out at the B3LYP
2
1
theory level using the Gaussian 98 program. Thus, the values given in Table 1 indicated that the energy
difference between the LUMO of quinones and the HOMO of nitrile oxides is smaller than that between
the HOMO of quinones and LUMO of nitrile oxides. This result suggests that the HOMO (nitrile
oxide)-LUMO (quinone) interaction is the governing factor of this reaction. On the other hand, the values
given in Table 2 indicated that the larger orbital coefficients were located at C-3 for quinones (1a), (1b)
and (1c) while they are at the oxygen atom for the nitrile oxides (2a) and (2b).
Table 1. Energy levels [eV] of FMO of carbazolequinones (1a-c) and nitrile oxides (2a,b).
Carbazolequinones
HOMO
- 6.065
- 6.201
- 6.201
- 6.338
- 6.650
LUMO
- 3.087
- 3.299
- 3.281
- 1.313
- 1.614
1
a
1
b
1
c
2
a
2
b
Table 2. Orbital coefficients of carbazolequinones (LUMO) and nitrile oxides (HOMO).
Carbazolequinones (LUMO)
C-2
0.185
C-3
0.221
1
a
1b
0.194
0.216
1
c
0.181
0.234
Nitrile oxides (HOMO)
Carbon atom
0.272
Oxygen atom
0.419
2
a
2b
0.288
0.426
The regiochemistry observed in the cycloaddition between 2-bromoquinone (1b) and nitrile oxides (2a)
and (2b) can not be explained by the values of the orbital coefficients but by the orienting effect of the
bromine atom. Indeed the oxygen atom of nitrile oxides attacks preferentially at C-2 of 1b. For
3
-bromoquinone (1c), both the values of the orbital coefficients and the regiocontrol effect of the bromine

HETEROCYCLES, Vol. 71, No. 1, 2007
31
atom orientate the cycloaddition to the formation of regioisomers (4a) or (4b) in which the oxygen atom
of nitrile oxides was linked to the brominated carbon of quinone (C-3).
Cycloaddition of carbazolequinones (1a), (1b) and (1c) with organic azides (5a) and (5b):
The unbrominated carbazolequinone (1a) reacted with an excess of benzyl azide (5a) in ethanol at room
temperature to afford a mixture of the two possible isomeric products (6a) and (7a) in 55 and 13% yield,
respectively. On the other hand, treatment of 1a with an excess of 4-methoxybenzyl azide (5b) in similar
conditions, gave regioisomers (6b) and (7b) in 20 and 7% yield, respectively (Scheme 3).
O
O
O
R
N
N
N
EtOH
rt
R N N N
+
N +
N
N
N
N
N
Et
Et
R
O
Et
O
O
5
5
a : R =
b : R =MeO
CH2
1
a
6a (55%)
7a (13%)
7b (7%)
CH2
6b (20%)
Scheme 3. Reaction of carbazolequinone (1a) with azides (5a) and (5b).
When 2-bromocarbazolequinone (1b) was treated with azides (5a) or (5b) in acetonitrile at room
temperature, we obtained the only regioisomers (6a) or (6b) in 50 and 43% yield, respectively.
Alternatively, treatment of 3-bromocarbazolequinone (1c) with azides (5a) or (5b) in ethanol at room
temperature gave a mixture of regioisomeric compounds (6a) (23%) and (7a) (51%) or (6b) (17%) and
(
7b) (31%) (Scheme 4).
O
R
N
O
O
O
O
N
Br
N
N
N
Et
N
Et
Et
Br
O
O
R
6a (23%)
6b (17%)
N
1
b
1c
N
R N N N
CH CN
EtOH
rt
O
N
Et
N
3
rt
N
N
O
5
a : R =
CH2
N
6
a (50%)
N
6b (43%)
5b : R =MeO
CH2
Et
R
O
7
7
a (51%)
b (31%)
Scheme 4. Reaction of bromocarbazolequinones (1b) and (1c) with azides (5a) and (5b).

32
HETEROCYCLES, Vol. 71, No. 1, 2007
1
13
For the regiochemistry assignment, we used the 2D H- C HMBC correlations for 6b and 7b (Figure 2).
4
In the case of 6b, J couplings were observed between C-4 and H of CH
2
of the ethyl group and between
C-10 and H of CH
2
of the methoxybenzyl group. In the case of 7b, both H of CH of the ethyl group and
2
4
H of CH of the methoxybenzyl group had J couplings with C-4.
2
H CO
3
O
9
1N
1
0
6
O
CH2
N
5
3
9
4
1N
N
N
10
6
N
5
CH2
3
H C
O
4
2
N
N
CH3
H C
O
2
CH3
6
b
7b
H CO
3
1
13
Figure 2. 2D H- C HMBC correlations
Moreover, IR spectra of the regioisomers (6a) and (6b) formed from the 2-bromocarbazolequinone (1b),
show two absorption bands for the carbonyl groups while in the regioisomers (7a) and (7b) formed in a
majority from the 3-bromocarbazolequinone (1c), the latter are not differentiated.
The respective LUMO and HOMO energy levels of carbazolequinones (1a), (1b) and (1c) given in Table
1
and LUMO and HOMO energy levels of azides (5a) and (5b) given in Table 3 indicated that the
HOMO (azide)-LUMO (quinone) interaction is the governing factor of this reaction. On the other hand,
the values of the orbital coefficients of azides given in Table 4 indicated that the larger orbital coefficients
were located at N-1 of 5a and 5b.
Table 3. Energy levels [eV] of FMO of azides (5a) and (5b).
Azides
HOMO
- 6.822
- 6.058
LUMO
- 0.827
- 0.724
5
a
5
b
Table 4. Orbital coefficients of azides (HOMO).
Azides
a
a
N-1
N-3
(
HOMO)
5
a
0.393
0.075
0.327
0.048
5b
a
R N N N
1
3

HETEROCYCLES, Vol. 71, No. 1, 2007
33
The regiochemistry observed in the cycloaddition of quinone (1a) and 2-bromoquinone (1b) with azides
5a) and (5b) agrees with the calculations. Indeed, N-1 of azides attacks at C-3 of quinones to give
(
preferentially or exclusively regioisomers (6a) and (6b). But, in the case of 3-bromoquinone (1c), N-1 of
azides adds preferentially to the unbrominated carbon C-2 of this quinone.
CONCLUSION
We
have
reported
the
regioselective
synthesis
of
isoxazolocarbazolequinone
and
triazolocarbazolequinone derivatives by 1,3-dipolar cycloaddition reactions of bromocarbazolequinones
respectively with nitrile oxides and azides. The regiochemistry observed in these reactions may be
explained by the orienting effect of the bromine atom independently of the values of the orbital
coefficients. Cycloadditions with nitrile oxides provide exclusively the regioisomers in which the oxygen
atom was linked to the brominated carbon of the carbazolequinone. In the case of azides, we obtained
preferentially or exclusively the regioisomers in which the N-1 atom was linked to the unbrominated
1
carbon of the carbazolequinone. The regiochemistry obtained was unambiguously confirmed by H-NMR
1
13
NOE experiments and 2D H- C HMBC correlations.
EXPERIMENTAL SECTION
1
. General: Melting points were measured with a Büchi apparatus (capillary tube). The IR spectra were
recorded with a Perkin-Elmer 1310 spectrophotometer. The NMR spectra were recorded with a Bruker
1
13
AM 300 spectrometer ( H-NMR: 300 MHz, C-NMR: 75 MHz). Chemical shifts (δ) are reported in ppm
using tetramethylsilane (TMS) as an internal reference. Coupling constant (J) values are given in Hz.
Elemental analyses were performed at the Centre de Microanalyse du CNRS at Solaize, France.
Calculations of the LUMO and HOMO energy and orbital coefficients were carried out at the B3LYP
theory level using the Gaussian 98 program.
2
. General procedure for the preparation of nitrile oxides (2a) and (2b) from aldoximes: A mixture
of benzaldehyde oxime (539 mg, 4.45 mmol) or 6-methylpyridine carbaldehyde oxime (605 mg, 4.45
mmol) and 13% aqueous solution of sodium hypochlorite (6 mL) in THF (6 mL) was stirred for 15
minutes at room temperature and the resulting green solution of 2a or 2b was dried with Na SO .
2
4
3
3
. [3+2]-Cycloadditions of nitrile oxides to carbazolequinones:
.1. 9-Ethyl-3-phenylisoxazolo[5,4-b]carbazole-4,10(9H)-dione (3a): The solution of nitrile oxide (2a)
prepared above was added dropwise to a stirred solution of 2-bromocarbazolequinone (1b) (152 mg, 0.5
mmol) in THF (10 mL). Stirring was maintained for 3 days at rt. The reaction mixture was evaporated to
2
dryness in vacuum and the resultant product was taken up in Et O to give a red precipitate of 3a which

34
HETEROCYCLES, Vol. 71, No. 1, 2007
2 2
was purified by column chromatography on silica gel with CH Cl /petroleum ether (1:1) as the eluent. It
-1
1
was obtained in 64% yield (110 mg). mp 244 °C. IR (KBr): 1673, 1658 cm . H NMR (300 MHz,
CDCl ): δ ppm 1.52 (t, J = 7.2 Hz, 3H, CH CH ), 4.74 (q, J = 7.2 Hz, 2H, CH CH ), 7.39 (m, 1H, 6-H),
3
2
3
2
3
1
3
7
.48 (m, 2H, 7-H and 8-H), 7.55 (m, 3H, Ar-H), 8.18 (m, 2H, Ar-H), 8.38 (d, J = 7.9 Hz, 1H, 5-H). C
NMR (75 MHz, CDCl ): δ ppm 15.61, 40.92, 111.47, 119.42, 120.44, 124.19, 124.70, 125.72, 126.97,
28.41, 129.01 (2C), 129.98 (2C), 131.47, 132.92, 140.26, 161.15, 167.43, 168.20, 177.24. Anal. Calcd
. 0.5 H O (351.36): C 71.79, H 4.30, N 7.97. Found: C 71.64, H 4.20, N 7.86.
3
1
for C21
H
14
N
2
O
3
2
3
.2. 5-Ethyl-3-phenylisoxazolo[4,5-b]carbazole-4,10(5H)-dione (4a): The solution of nitrile oxide (2a)
prepared above was added dropwise to a stirred solution of 3-bromocarbazolequinone (1c) (152 mg, 0.5
mmol) in THF (10 mL). Stirring was maintained for 3 days at rt. The reaction mixture was evaporated to
2
dryness in vacuum and the resultant product was taken up in Et O to give a red precipitate of 4a which
was purified by column chromatography on silica gel with EtOAc/petroleum ether (3:1) as the eluent. It
-1 1
was obtained in 69% yield (118 mg). mp 241 °C. IR (KBr): 1667 cm . H NMR (300 MHz, CDCl
ppm 1.47 (t, J = 7.1 Hz, 3H, CH CH ), 4.73 (q, J = 7.1 Hz, 2H, CH CH ), 7.42 (m, 1H, 8-H), 7.48 (m, 2H,
-H and 7-H), 7.56 (m, 3H, Ar-H), 8.09 (m, 2H, Ar-H), 8.37 (d, J = 7.1 Hz, 1H, 9-H) ppm. C NMR (75
MHz, CDCl ): δ ppm 15.50, 40.98, 111.66, 117.72, 118.00, 123.79, 124.100, 126.008, 126.90, 127.81,
29.02 (2C), 129.75 (2C), 131.50, 135.73, 139.57, 161.00, 168.724, 170.50, 175.01. Anal. Calcd for
. 0.1 H O (344.15): C 73.29, H 4.16, N 8.14. Found: C 73.35, H 4.19, N 8.19.
3
): δ
2
3
2
3
1
3
6
3
1
C
21
H
14
N
2
O
3
2
3
.3. 9-Ethyl-3-(6-methylpyridin-2-yl)isoxazolo[5,4-b]carbazole-4,10(9H)-dione (3b): The solution of
nitrile oxide (2b) prepared above was added dropwise to a stirred solution of 2-bromocarbazolequinone
1b) (152 mg, 0.5 mmol) in THF (10 mL). Stirring was maintained for 3 days at rt. The reaction mixture
was evaporated to dryness in vacuum and the resultant product was taken up in Et O to give a red
precipitate of 3b which was purified by column chromatography on silica gel with EtOAc/CH Cl (1:1)
(
2
2
2
-1 1
as the eluent. It was obtained in 58% yield (103 mg). mp 224 °C. IR (KBr): 1673 cm . H NMR (300
MHz, CDCl ): δ ppm 1.52 (t, J = 7.2 Hz, 3H, CH CH ), 2.71 (s, 3H, 6’-CH ), 4.73 (q, J = 7.2 Hz, 2H,
CH CH ), 7.34 (d, J = 7.8 Hz, 1H, 5’-H), 7.38 (m, 1H, 6-H), 7.48 (m, 2H, 7-H and 8-H), 7.81 (t, J = 7.8
Hz, 1H, 4’-H), 8.12 (d, J = 7.8 Hz, 1H, 3’-H), 8.36 (d, J = 8.2 Hz, 1H, 5-H). C NMR (75 MHz, CDCl
δ ppm 15.61, 25.09, 40.96, 111.51, 119.64, 120.43, 123.19, 124.18, 124.68, 125.56, 125.75, 128.45,
3
2
3
3
2
3
1
3
3
):
1
32.99, 137.35, 140.28, 146.04, 159.73, 160.55, 167.33, 168.07, 176.91. Anal. Calcd for C H N O . 0.1
21 15 3 3
2
H O (359.17): C 70.23, H 4.27, N 11.70. Found: C 70.24, H 4.30, N 11.66.
3
.4. 5-Ethyl-3-(6-methylpyridin-2-yl)isoxazolo[4,5-b]carbazole-4,10(5H)-dione (4b): The solution of
nitrile oxide (2b) prepared above was added dropwise to a stirred solution of 3-bromocarbazolequinone

HETEROCYCLES, Vol. 71, No. 1, 2007
35
(
1c) (152 mg, 0.5 mmol) in THF (10 mL). Stirring was maintained for 3 days at rt. The reaction mixture
was evaporated to dryness in vacuum and the resultant product was purified by column chromatography
on silica gel with EtOAc/ petroleum ether (1:3) as the eluent. 4b was obtained in 35% yield (64 mg). mp
-1 1
2
21 °C. IR (KBr): 1673 cm . H NMR (300 MHz, CDCl
s, 3H, 6’-CH ), 4.70 (q, J = 7.2 Hz, 2H, CH CH ), 7.35 (d, J = 7.8 Hz, 1H, 5’-H), 7.42 (m, 1H, 8-H),
.47 (m, 2H, 6-H and 7-H), 7.80 (t, J = 7.8 Hz, 1H, 4’-H), 7.88 (d, J = 7.8 Hz, 1H, 3’-H), 8.34 (d, J = 7.8
3
): δ ppm 1.47 (t, J = 7.2 Hz, 3H, CH
2 3
CH ), 2.71
(
3
2
3
7
1
3
Hz, 1H, 9-H). C NMR (75 MHz, CDCl
3
): δ ppm 15.44, 25.05, 40.96, 111.68, 117.68, 118.35, 122.68,
1
1
4
23.74, 124.09, 125.52, 126.00, 127.79, 135.72, 137.35, 139.51, 146.07, 159.71, 160.47, 168.48, 170.30,
74.43. Anal. Calcd for C21
.37, N 11.49.
15 3 3 2
H N O . 0.3 H O (362.77): C 69.53, H 4.33, N 11.58. Found: C 69.68, H
3.5. [3+2]-Cycloaddition of nitrile oxide (2a) to carbazolequinone (1a): The solution of nitrile oxide
(
2a) prepared above was added dropwise to a stirred solution of carbazolequinone (1a) (113 mg, 0.5
mmol) in THF (10 mL). Stirring was maintained for 3 days at rt. The reaction mixture was evaporated to
dryness in vacuum to yield a mixture of regioisomeric compounds (3a) and (4a) which were separated by
column chromatography on silica gel using, first CH
2 2
Cl / petroleum ether (1:1) and then, EtOAc/
petroleum ether (3:1) as the eluent. 3a was obtained in 24% yield (41 mg) and 4a in 24% yield (41 mg).
3.6. [3+2]-Cycloaddition of nitrile oxide (2b) to carbazolequinone (1a): The solution of nitrile oxide
(
2b) prepared above was added dropwise to a stirred solution of carbazolequinone (1a) (113 mg, 0.5
mmol) in THF (10 mL). Then, basic alumina (1g) was added. Stirring was maintained for 3 days at rt.
After filtration, the solvent was evaporated to yield a mixture of regioisomeric compounds (3b) and (4b)
which were separated by column chromatography on silica gel using, first EtOAc/ petroleum ether (1:3)
2 2
and then, EtOAc/ CH Cl (1:1) as the eluent. 3b was obtained in 25% yield (45 mg) and 4b in 25% yield
(
45 mg).
4
General procedure for the preparation of azides (5a) and (5b): To a solution of sodium azide (480
mg, 7.38 mmol) in EtOH (50 mL) was added benzyl bromide (1130 mg, 6.61 mmol) or 4-methoxybenzyl
bromide (1330 mg, 6.61 mmol). The solution was heated at reflux for 24 h, cooled, diluted with water (40
2 2 4
mL) and extracted with Et O (3 × 30 mL). The combined organic solution was dried with Na SO and
concentrated to provide colourless viscous oil of benzyl or 4-methoxybenzyl azide which was used
without further purification.
4
.1. 1-Benzyl-5-ethyl[1,2,3]triazolo[4,5-b]carbazole-4,10(1H,5H)-dione (6a): The benzyl azide (5a)
prepared above was added dropwise to a stirred solution of 2-bromocarbazolequinone (1b) (152 mg, 0.5
mmol) in MeCN (10 mL). Stirring was maintained for 4 days at rt. The orange reaction suspension was

36
HETEROCYCLES, Vol. 71, No. 1, 2007
concentrated in vacuum then filtered to yield compound (6a) as an orange solid which was purified by
recristallization from EtOH. It was obtained in 50% yield (90 mg). mp 279 °C. IR (KBr): 1678, 1667,
-
1 1
1
652 cm . H NMR (300 MHz, CDCl
CH CH ), 5.98 (s, 2H, CH ), 7.35 (m, 3H), 7.46 (m, 3H), 7.53 (m, 2H), 8.33 (d, J = 7.2 Hz, 1H, 9-H). C
NMR (75 MHz, CDCl ): δ ppm 15.51, 40.95, 53.72, 111.66, 118.00, 123.64, 124.37, 125.81, 127.72,
29.08 (2C), 129.27, 129.35 (2C), 134.65 (2C), 135.48, 139.47, 145.95, 172.67, 172.90. Anal. Calcd for
. 0.4 H O (363.59): C 69.37, H 4.66, N 15.41. Found C 69.41, H 4.44, N 15.48.
3
): δ ppm 1.48 (t, J = 7.0 Hz, 3H, CH
2 3
CH ), 4.76 (q, J = 7.0 Hz, 2H,
1
3
2
3
2
3
1
C
21
H
16
N
4
O
2
2
4
4
2
.2. 5-Ethyl-1-(4-methoxybenzyl)[1,2,3]triazolo[4,5-b]carbazole-4,10(1H,5H)-dione (6b): The
-methoxybenzyl azide (5b) prepared above was added dropwise to a stirred solution of
-bromocarbazolequinone (1b) (152 mg, 0.5 mmol) in acetonitrile (10 mL). Stirring was maintained for 3
days at rt. The orange reaction suspension was evaporated to dryness in vacuum and the resultant product
was taken up in diethyl ether to give an orange precipitate of 6b which was filtered and purified by
column chromatography on silica gel with CH
2
Cl
3% yield (82 mg). mp 292 °C. IR (KBr): 1679, 1668, 1655 cm . H NMR (300 MHz, CDCl
.48 (t, J = 6.9 Hz, 3H, CH CH ), 3.80 (s, 3H, OCH ), 4.76 (q, J = 6.9 Hz, 2H, CH CH ), 5.93 (s, 2H,
), 6.90 (d, J = 8.52 Hz, 2H, Ar-H), 7.45 (m, 1H, 8-H), 7.49 (m, 2H, Ar-H), 7.52 (d, J = 8.2 Hz, 2H,
2
/ petroleum ether (2:1) as the eluent. It was obtained in
-1 1
4
1
3
): δ ppm
2
3
3
2
3
CH
2
1
3
Ar-H), 8.38 (d, J = 7.6 Hz, 1H, 9-H). C NMR (75 MHz, CDCl
3
): δ ppm 15.37, 40.86, 53.26, 55.65,
11.55, 114.74 (2C), 118.85, 123.67, 124.45, 125.67, 126.96, 127.60, 130.58 (2C), 134.56, 135.60,
39.52, 146.01, 160.51, 172.73, 172.86. Anal. Calcd for C22 . 0.6 H O (397.22): C 66.52, H 4.87,
1
1
H
18
N
4
O
3
2
N 14.10. Found: C 66.57, H 4.64, N 13.96.
4
.3. [3+2]-Cycloadditions of benzyl azides (5a) to 3-bromocarbazolequinones (1c): The benzyl azide
5a) prepared above was added dropwise to a stirred solution of 3-bromocarbazolequinone (1c) (152 mg,
.5 mmol) in EtOH (5 mL). Stirring was maintained for 2 weeks at rt. The orange reaction suspension
was concentrated in vacuum then filtered to yield an orange solid of a mixture of regioisomeric
compounds (6a) and (7a) which were separated by column chromatography on silica gel with CH Cl
petroleum ether (1:1) as the eluent. 6a was obtained in 23% yield (40 mg) and 7a in 51% yield (90 mg).
(
0
2
2
/
3
-Benzyl-5-ethyl[1,2,3]triazolo[4,5-b]carbazole-4,10(3H,5H)-dione (7a): mp 273 °C. IR (KBr): 1666
-1 1
cm . H NMR (300 MHz, CDCl
): δ ppm 1.48 (t, J = 7.2 Hz, 3H, CH CH ), 4.67 (q, J = 7.2 Hz, 2H,
2 3
3
CH CH ), 5.94 (s, 2H, CH ), 7.51 (m, 2H, Ar-H), 7.60 (m, 6H, Ar-H), 8.40 (dd, J = 7.9 Hz and J = 1.1 Hz,
2
3
2
1
3
1
1
H, 9-H). C NMR (75 MHz, CDCl
28.24, 128.96 (2C), 129.33, 129.38 (2C), 133.56, 133.95, 134.48, 139.96, 147.12, 170.41, 175.44. Anal.
. 0.2 H O (359.99): C 70.07, H 4.59, N 15.56. Found: C 70.10, H 4.42, N 15.55.
3
): δ ppm 15.56, 40.84, 53.93, 111.25, 119.97, 124.42 (2C), 125.57,
Calcd for C21
H
16
N
4
O
2
2

HETEROCYCLES, Vol. 71, No. 1, 2007
37
4
4
3
.4. [3+2]-Cycloadditions of 4-methoxybenzyl azides (5b) to 3-bromocarbazolequinones (1c): The
-methoxybenzyl azide (5b) prepared above was added dropwise to a stirred solution of
-bromocarbazolequinone (1c) (152 mg, 0.5 mmol) in ethanol (5 mL). Stirring was maintained for 10
days at rt. The orange reaction mixture was evaporated to dryness in vacuum and the resultant product
was taken up in Et O then filtered to give an orange precipitate of a mixture of regioisomeric compounds
6b) and (7b) which were separated by column chromatography on silica gel with CH Cl / petroleum
ether (2:1) as the eluent. 6b was obtained in 17% yield (30 mg) and 7b in 30% yield (53 mg).
2
(
2
2
5
-Ethyl-3-(4-methoxybenzyl)[1,2,3]triazolo[4,5-b]carbazole-4,10(3H,5H)-dione (7b): mp 270 °C. IR
-
1 1
(
KBr): 1666 cm . H NMR (300 MHz, CDCl
CH ), 4.69 (q, J = 7.2 Hz, 2H, CH CH ), 5.88 (s, 2H, CH
Ar-H), 7.42 (m, 2H, Ar-H), 7.46 (d, J = 8.5 Hz, 2H, Ar-H), 8.43 (d, J = 7.8 Hz, 1H, 9-H). C NMR (75
MHz, CDCl ): δ ppm 15.33, 40.58, 53.25, 55.46, 110.98, 114.42 (2C), 119.75, 124.21 (2C), 125.32,
26.40, 127.98, 130.31 (2C), 133.16, 133.75, 139.72, 146.92, 160.20, 170.26, 175.24. HRMS: calcd. for
386.1379; found 386.13736.
3
): δ ppm 1.49 (t, J = 7.2 Hz, 3H, CH
2 3
CH ), 3.78 (s, 3H,
3
2
3
2
), 6.88 (d, J = 8.5 Hz, 2H, Ar-H), 7.35 (m, 1H,
1
3
3
1
22 18 4 3
C H N O
4
.5. [3+2]-Cycloaddition of azide (5a) to carbazolequinone (1a): The benzyl azide (5a) prepared above
was added dropwise to a stirred solution of carbazolequinone (1a) (113 mg, 0.5 mmol) in EtOH (5 mL).
Stirring was maintained for 2 weeks at rt. The orange reaction suspension was concentrated in vacuum
then filtered to yield a mixture of regioisomeric compounds (6a) and (7a) which were separated by
column chromatography on silica gel with CH
2
Cl
2
/ petroleum ether (1:1) as the eluent. 6a was obtained in
5
5% yield (98 mg) and 7a in 13% yield (23 mg).
4
.6. [3+2]-Cycloaddition of azide (5b) to carbazolequinone (1a): The 4-methoxybenzyl azide (5b)
prepared above was added dropwise to a stirred solution of carbazolequinone (1a) (113 mg, 0.5 mmol) in
ethanol (5 mL). Stirring was maintained for 2 weeks at rt. The orange reaction mixture was evaporated to
2
dryness in vacuum and the resultant product was taken up in Et O then filtered to give an orange
precipitate of a mixture of regioisomeric compounds (6b) and (7b) which were separated by column
chromatography on silica gel with CH Cl / petroleum ether (2:1) as the eluent. 6b was obtained in 20%
2
2
yield (39 mg) and 7b in 7% yield (14 mg).
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