A New and Facile Method for the Synthesis of Nitrocarbazoles by Urea Nitrate

Article abstract of DOI:10.1081/SCC-120030313

Urea nitrate in acetic acid is found to be an effective and mild nitrating agent for the preparation of mono nitrocarbazoles.

Full text of DOI:10.1081/SCC-120030313

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A New and Facile Method for the Synthesis of
Nitrocarbazoles by Urea Nitrate
Rajagopal Nagarajan a , D. Muralidharan a & Paramasivan T. Perumal a
a Organic Chemistry Division , Central Leather Research Institute , Adyar, Chennai, 600
020, India
Published online: 21 Aug 2006.
To cite this article: Rajagopal Nagarajan , D. Muralidharan & Paramasivan T. Perumal (2004) A New and Facile Method
for the Synthesis of Nitrocarbazoles by Urea Nitrate, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:7, 1259-1264, DOI: 10.1081/SCC-120030313
To link to this article: http://dx.doi.org/10.1081/SCC-120030313
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 7, pp. 1259–1264, 2004
A New and Facile Method for the Synthesis
of Nitrocarbazoles by Urea Nitrate
Rajagopal Nagarajan, D. Muralidharan, and
*
Paramasivan T. Perumal
Organic Chemistry Division, Central Leather Research Institute,
Chennai, India
ABSTRACT
Urea nitrate in acetic acid is found to be an effective and mild nitrating
agent for the preparation of mono nitrocarbazoles.
Key Words: Acetylation; Urea nitrate; Nitration; Carbazoles;
Nitrocarbazoles.
INTRODUCTION
The synthesis of substituted carbazoles[1] has attracted considerable
attention in recent years as this class of compounds constitute structural
*
Correspondence: Paramasivan T. Perumal, Organic Chemistry Division, Central
Leather Research Institute, Adyar, Chennai 600 020, India; Fax: 91-44-24911589;
E-mail: ptperumal@hotmail.com.
1259
DOI: 10.1081/SCC-120030313
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Nagarajan, Muralidharan, and Perumal
frameworks of several naturally occurring bioactive alkaloids. In particular,
acetylcarbazoles have been used to synthesize condensed carbazole hetero-
cycles, alkaloids etc.
The acetylation of 9-ethyl carbazole with acetyl chloride catalyzed by
AlCl3 had been reported[2] to give a mixture of 3- and 3,6-diacetyl derivatives
and large amount of tarry products, which was attributed to high acidity of
AlCl3. In continuation of our interest on InCl3 catalyzed reactions,[3] the
acetylation of carbazoles was studied.
The reaction of 9-ethylcarbazole with excess acetic anhydride in the pres-
ence of 20 mol% InCl3 for 2 hr revealed (TLC), the 3-acetylated derivative
with no traces of diacetylcarbazole. In addition, a small quantity of tarry
material was observed. Similar results were observed with In(OTf)3.
Recently, we have found that urea nitrate is an efficient catalyst for imino
Diels–Alder reaction[4] and aromatization of 1,4-dihydropyridines.[5] In order
to evaluate the catalytic efficiency of urea nitrate for acetylation, the reaction
was repeated for 9-ethylcarbazole with acetic anhydride in the presence of
urea nitrate. TLC shows the formation of a new yellow product (16% yield
was obtained with 20 mol% of urea nitrate). Analysis of the new product
showed that the compound was 3-nitro-9-ethylcarbazole. Based on these find-
ings it was proposed that acetic acid formed or present in acetic anhydride may
be the proton source, which reacted with urea nitrate, thereby effected the
nitration (Sch. 1).
Literature survey[6] on nitration of carbazoles revealed that 3- and
6-positions of carbazole were the most reactive with the 1- and 8-positions
being less reactive particularly towards nitration. Lindeman[7] found that treat-
ment of carbazole in acetic acid with NaNO2 followed by nitric acid yielded
principally 3-nitro-9-nitrosocarbazole which on heating with KOH or glacial
acetic acid gave 3-nitrocarbazole. Other nitration methods include the use of
conc. HNO3 or C(NO2)4 under photochemical conditions.[9] Exhaustive
[8]
nitration gives 1,3,6,8-tetranitro carbazole.[10] The nitration of carbazole
with conc. nitric acid yielded dinitrocarbazoles.[11]
The methodology of nitration with acetic acid and urea nitrate was
extended to other substituted carbazoles. Most of carbazole derivatives
Scheme 1.

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Synthesis of Nitrocarbazoles by Urea Nitrate
1261
underwent nitration reaction in a short period of time (except for 3-substituted
carbazoles which required acidic conditions achieved by addition of few drops
of 10% sulfuric acid in acetic acid) in good yields (Table 1). In mother liquor a
trace amount of 1-nitrocarbazoles was found.
Finally, we have shown that urea nitrate–acetic acid combination is a
mild, selective and efficient reagent for nitration of carbazole (Sch. 2).
EXPERIMENTAL
Analytical TLC was performed on precoated sheets of silica gel G of
0.25 mm thickness containing PF 254 indicator. Column chromatography
was performed with silica gel (60–120 mesh). IR spectra were recorded as
KBr pellets on FTIR spectrometer. 1H NMR spectra were recorded at
300 MHz in CDCl3 and the chemical shifts are given in d relative to the
solvent (77.0).
Typical Procedure for Acetylation
To a stirred mixture of carbazole (0.5 g, 2.56 mmol) and acetic anhydride
(7.69 mmol) in CH2Cl2 (10 mL), InCl3 or In(OTf)3 (0.51 mmol) was added and
stirred for appropriate time. Water (50 mL) was added to the reaction mixture,
extracted with CH2Cl2 (3 Â 10 mL) and dried with anhydrous Na2SO4. The
solvent was distilled off and the residue chromatographed over silica gel by
eluting with ethyl acetate : petroleum ether (1 : 9) to give the acetyl carbazoles.
3-Acetyl-9-ethylcarbazole (2). 0.358 g (59%) of colorless needles; m.p.
115–1168C (Lit.[2] 115); IR: 3046, 2921, 1667, 1593, 1495, 1351, 1170,
Table 1. Synthesis of nitrocarbazoles.
Substituents
Time
(min)
Yield
(%)
Carbazole
R1
R2
1a
1b
1c
1d
1e
H
CH3
H
10a
20
86
83
81
92
85
H
C2H5
C2H5
C2H5
H
20
CH3
CHO
10b
15b
aDue to limited solubility of carbazole at r.t., the reaction is conducted at 708C.
bThe three substituted carbazole requires few drops (0.4 mL) of 10% conc.
H2SO4 in glacial acetic acid.

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Nagarajan, Muralidharan, and Perumal
Scheme 2.
1
838 cm21; H NMR (300MHz, CDCl3): d 8.75 (d, 1H, J ¼ 1.2 Hz), 8.18
(m, 2H), 7.50 (t, 1H, J ¼ 7.1 Hz), 7.46–7.26 (m, 3H), 4.42 (q, 2H,
J ¼ 7.2 Hz), 2.73 (s, 3H), 1.46 (t, 3H, J ¼ 7.2 Hz); 13C NMR (75 MHz,
CDCl3): d 197.2, 142.2, 140.2, 128.3, 126.0, 122.8, 122.2, 121.4, 120.2,
119.5, 108.5, 107.6, 107.4, 37.3, 26.1, 13.3; Mass m/z 237 (Mþ); Anal. Calcd
for C16H15NO; C, 80.98; H, 6.37; N, 5.90; Found, C, 81.22; H, 6.48; N, 6.76.
Typical Procedure for Nitration of Carbazoles
To a stirred solution of carbazole (3 mmol) in acetic acid (10 mL), urea
nitrate (3 mmol) was added and stirred for appropriate time. After the reaction
was over, the precipitate formed by the addition of water was filtered and
dried. The crude product was recrystallized from acetic acid to give
nitrocarbazoles.
3-Nitrocarbazole (3a). 0.547 g (86%) of yellow crystals; m.p. 215–
2168C (Lit.[12] 215–216); IR: 3334, 3033, 1605,1580, 1500, 1457, 1313,
1
722 cm21; H NMR (300 MHz, DMSO-d6): d 12.05 (brs, 1H, NH), 9.14
(d, 1H, J ¼ 2.4 Hz), 8.36 (d, 1H, J ¼ 10.4 Hz), 8.30 (dd, 1H, J1 ¼ 2.4 Hz,
J2 ¼ 11.6 Hz), 7.63–7.47 (m, 3H), 7.30 (t, 1H, J ¼ 9.6 Hz); 13C NMR
(75 MHz, DMSO-d6): d 143.3, 141.0, 139.8, 127.3, 122.5, 122.2, 121.4,
121.3, 120.3, 117.4, 111.9, 111.1; Mass m/z 212 (Mþ); Anal. Calcd for
C12H8N2O2; C, 67.92; H, 3.80; N, 13.20; Found, C, 67.76; H, 3.87; N, 13.09.
3-Nitro-9-methylcarbazole (3b). 0.563 g (83%) of yellow needles; m.p.
174–1758C (Lit.[12] 173–174); IR: 3082, 2924, 1593, 1510,1472, 1317,
1
744 cm21; H NMR (300 MHz, CDCl3): d 8.82 (d, 1H, J ¼ 2.1 Hz), 8.27
(dd, 1H, J1 ¼ 2.2 Hz, J2 ¼ 9.0 Hz), 8.00 (d, 1H, J ¼ 7.8 Hz), 7.51 (t, 1H,
J ¼ 7.4 Hz), 7.36–7.17 (m, 4H), 3.77 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 143.8, 142.0, 140.4, 127.4, 122.6, 122.3, 121.5, 120.8, 120.7, 117.1,
109.4, 107.9, 29.5; Mass m/z 226 (Mþ); Anal. Calcd for C13H10N2O2; C,
69.02; H, 4.46; N, 12.38; Found, C, 69.39; H, 4.38; N, 12.12.

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Synthesis of Nitrocarbazoles by Urea Nitrate
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3-Nitro-9-ethylcarbazole (3c). 0.583 g, (81%) of yellow crystalline
solid; m.p. 127–1288C (Lit.[12] 126–127); IR: 3048, 2930, 1591, 1510,
1
1471, 1313, 749 cm21; H NMR (300 MHz, CDCl3): d 8.96 (d, 1H, J ¼
1.9 Hz), 8.38 (dd, 1H, J1 ¼ 2.0 Hz, J2 ¼ 12.5 Hz), 8.13 (d, 1H, J ¼ 7.8 Hz),
7.60 (t, 1H, J ¼ 7.6 Hz), 7.48 (m, 3H), 4.43 (q, 2H, J ¼ 7.1 Hz), 1.47 (t, 3H,
J ¼ 7.2 Hz); 13C NMR (75 MHz, CDCl3): d 143.0, 141.1, 140.6, 127.4, 122.9,
122.6, 121.6, 121.0, 120.7, 117.3, 109.4, 107.9, 38.1, 13.8; Mass m/z 240
(Mþ); Anal. Calcd for C14H12N2O2; C, 69.99; H, 5.03, N, 11.66; Found, C,
70.24; H, 4.93; N, 11.53.
3-Methyl-6-nitro-9-ethylcarbazole (3d). 0.701 g (92%) of yellow solid;
m.p. 89–908C; IR: 3093, 2965, 1598, 1487, 1385, 1307, 800 cm21; 1H NMR
(300 MHz, CDCl3): d 8.88 (d, 1H, J ¼ 2.2 Hz), 8.32 (dd, 1H, J1 ¼ 2.2 Hz,
J2 ¼ 9.0 Hz), 8.06 (d, 1H, J ¼ 7.7 Hz), 7.57 (t, 1H, J ¼ 8.1 Hz), 7.44–7.24
(m, 2H), 4.36 (q, 2H, J ¼ 7.2 Hz), 2.56 (s, 3H), 1.43 (t, 3H, J ¼ 7.2 Hz);
13C NMR (75 MHz, CDCl3): d 142.7, 140.9, 140.2, 127.2, 122.6, 122.3,
121.3, 120.8, 120.5, 117.0, 109.3, 107.8, 37.9, 21.5, 13.7; Mass m/z 254
(Mþ); Anal. Calcd for C15H14N2O2; C, 70.85; H, 5.55; N, 11.02; Found, C,
70.66; H, 5.61; N, 10.86.
6-Nitro-9-ethylcarbazole-3-aldehyde (3e). 0.683 g (85%) of yellow
solid; m.p. 247–2488C (Lit.[13] 248) IR: 3076, 2964, 1687, 1627, 1593,
1509, 1483, 1383, 1311, 723 cm21 1H NMR (300 MHz, DMSO-d6): d
;
10.14 (s, 1H, CHO), 9.04 (s, 1H), 8.65 (s, 1H), 8.46 (d, 1H, J ¼ 8.5 Hz),
8.14 (d, 1H, J ¼ 8.0 Hz), 7.60–7.49 (m, 2H), 4.89 (q, 2H, J ¼ 7.1 Hz), 1.53
(t, 3H, J ¼ 7.1 Hz); 13C NMR (75 MHz, DMSO-d6): d 192.2, 144.7, 143.9,
141.1, 129.9, 128.1, 125.6, 122.7, 122.5, 122.4, 118.2, 111.1, 110.5, 38.4,
14.1; Mass m/z 268 (Mþ); Anal. Calcd for C15H12N2O3; C, 67.16; H, 4.51;
N, 10.44; Found, C, 66.89; H, 4.65; N, 10.23.
ACKNOWLEDGMENT
We thank the Council of Scientific and Industrial Research, New Delhi,
India for financial support.
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Received in India October 17, 2003

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