Synthesis of a new heterocyclic system - Fluoreno[1,2-d]imidazol-10-one

Article abstract of DOI:10.1139/V09-062

Synthesis of various substituted fluoreno[1,2-d]imidazol-10-ones (5a-5g) has been accomplished by the cyclization of diazotized 1-substituted 4-benzoyl-5- aminobenzimidazoles (4a-4g). Compounds 4a-4g were prepared by reductive ring opening of 3H-imidazo[4

Full text of DOI:10.1139/V09-062

724
Synthesis of a new heterocyclic system —
Fluoreno[1,2-d]imidazol-10-one
Mohammad Rahimizadeh, Mehdi Pordel, Mehdi Bakavoli, Shima Rezaeian, and
Hossein Eshghi
Abstract: Synthesis of various substituted fluoreno[1,2-d]imidazol-10-ones (5a–5g) has been accomplished by the cycliza-
tion of diazotized 1-substituted 4-benzoyl-5- aminobenzimidazoles (4a–4g). Compounds 4a–4g were prepared by reductive
ring opening of 3H-imidazo[4’,5’:3,4]benzo[c]isoxazoles (3a–3g) with zinc dust in EtOH/NaOH solution.
Key words: fluoreno[1,2-d]imidazol-10-ones, diazotation, imidazo[4’,5’:3,4]benzo[c]isoxazoles, reductive ring opening.
´
´
´
´
`
´
´
´
`
Resume : On a realise la synthese de diverses fluoreno[1,2-d]imidazol-10-ones substituees, 5a–5g, en procedant a la cycli-
´ ´
´
´
sation de 4-benzoyl-5-aminobenzimidazoles diazotes, substitues en position 1, 4a–4g. Les produits 4a–4g ont ete obtenus
´
par l’ouverture reductrice de cycle de 3H-imidazo[4’,5’:3,4]benzo[c]isoxazoles, 3a–3g, avec de la poudre de zinc dans une
solution EtOH/NaOH.
´
´
´
Mots-cles : fluoreno[1,2-d]imidazol-10-ones, diazotation, imidazo[4’,5’:3,4]benzo[c]isoxazoles, ouverture reductrice de cycle.
´
[Traduit par la Redaction]
ested in examining the cyclization of diazotized compounds
4a–4g to new fluoreno[1,2-d]imidazol-10-ones (5a–5g).
Introduction
Fluorenones (fluorine-9-ones) are among the oldest
classes of bioactive compounds, which are widely used as
antiviral1–3 and anticancer4,5 agents and act as the key syn-
thetic intermediates in many reactions.6,7 Also, fluorenones
with a suitable functionality can be used as a fluorescent
electrophilic reagent.8 Recently, they have mainly been con-
sidered as an important unit in polymer chemistry.9–12 The
fluorenone structural unit provides both rigidly planarized
biphenyl units within the polymer backbone and the possi-
bility of remote functionalization at C-9, the latter offer the
prospect of improving both polymer processibility and medi-
ating potential interchain interactions in films.13
There are several methods for the synthesis of these use-
ful compounds, including the Friedel–Crafts ring closures of
biarylcarboxylic acid derivatives,14,15 intramolecular [4+2]
cycloaddition reactions of conjugated enynes,16 oxidation of
fluorenes,17 remote metalation of m-teraryl and biaryl
amides18 or combined directed ortho metalation-directed re-
mote metalation,19 palladium-catalyzed cyclocarbonylation
of ortho halobiaryls,20 and several other new methods.21–23
Intramolecular reaction of diazotized 2-aminobenzophenones
is one of the oldest methods for the preparation of fluore-
nones with relatively well-clarified mechanistic features.24
A literature survey disclosed that the diazotized 4-benzoyl-
5-aminobenzimidazoles have not been converted to fluo-
reno[1,2-d]imidazol-10-ones. Owing to our growing interest
in the synthesis of bioactive heterocycles,25 we became inter-
Results and discussion
The new 3H-imidazo[4’,5’:3,4]benzo[c]isoxazoles (3a–3g)
were obtained via the nucleophilic substitution of hydrogen
of 1-alkyl-5-nitrobenzimidazoles (1a–1c) with arylacetoni-
triles (2a–2d) in basic MeOH solution26 (Scheme 1). The re-
action does not occur when R2 is an electron-withdrawing
group, since the conjugated base of 2d is a weak nucleo-
phile.
The reductive ring opening of benzo[c]isoxazoles has
been reported with Fe/HOAC27 and Raney Ni/N2H4ÁH2O28
methods. Herein, we introduce the reduction of
benzo[c]isoxazoles with zinc dust in EtOH and 20% NaOH
solution as a highly efficient route to the synthesis of new
key intermediates 4a–4g in excellent yields and short reac-
tion times (Scheme 2).
Diazotized compounds 4a–4g underwent cyclization in
moderate-to-high yields to new fluoreno[1,2-d]imidazol-10-
ones (5a–5g) at 70 8C (Scheme 3). The yield of reaction
varies with the nature of the substituent on the benzoyl ring
and is better with electron-donating groups (EDGs), since
with EDGs, the electron density of the aromatic ring is
higher, and it can act as a better nucleophile.
The structural assignments of compounds 5a–5g were
based on the analytical and spectral data. For example, in
1
the H NMR spectrum of 5c, the signal at d 4.16 ppm, as-
signable to exchangeable protons (NH2 group), and two dou-
blet signals at d 6.78 ppm and d 7.36 ppm, attributed to four
aromatic protons of p-methoxyphenyl ring of compound 4c,
are not present. Instead, there are the doublet of doublet sig-
nal at d 6.64 ppm (J = 8.1 Hz and J’ = 2.1 Hz), the doublet
signal at d 7.03 ppm with meta J (2.1 Hz), and the doublet
signal at d 7.66 ppm with ortho J (8.1 Hz), assignable to
three aromatic protons of methoxyphenyl ring. Moreover,
Received 17 September 2008. Accepted 6 January 2009.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 23 May 2009.
M. Rahimizadeh,1 M. Pordel, M. Bakavoli, S. Rezaeian, and
H. Eshghi. Department of Chemistry, School of Sciences,
Ferdowsi University of Mashhad, Mashhad 91775-1436, Iran.
1Corresponding author (e-mail: rahimizh@yahoo.com).
Can. J. Chem. 87: 724–728 (2009)
doi:10.1139/V09-062
Published by NRC Research Press

Rahimizadeh et al.
725
Scheme 1.
Scheme 2.
Scheme 3.
the FTIR spectrum of 5c in KBr did not show the absorption
band at 3320 cm–1, corresponding to NH2 group. All these
evidences plus the molecular-ion peak at m/z 278 and micro-
analytical data strongly support the tetracyclic structure of
compound 5c.
trometer, and only noteworthy absorptions are listed. The
1H NMR (100 MHz) spectra were recorded on a Bruker AC
100 spectrometer. Chemical shifts are reported in ppm
downfield from TMS as internal standard; coupling con-
stance J are given in Hz. The mass spectra were recorded
on a Varian Mat. CH-7 at 70 eV. Elemental analysis was
performed on a Thermo Finnigan Flash EA microanalyzer.
Conclusion
In summary, this research has demonstrated that the cycli-
zation of diazotized o-amino-ketones is a reliable work,
which can be extended to the synthesis of other new hetero-
cyclic compounds.
Synthesis of imidazo[4’,5’:3,4]benzo[c]isoxazoles (3a–3g)
General procedure
Compounds 1a–1c (10 mmol) and 2a–2c (12 mmol) were
added with stirring to a solution of KOH (20 g, 357 mmol)
in methanol (80 mL). The mixture was refluxed with stirring
for 4 h, and then poured into water. The precipitate was col-
lected by filtration, washed with water, and air-dried to give
3a–3g.
Experimental
CH2Cl2 and MeOH were distilled from CaH2. Silica gel
60 (0.040–0.063 mm, Merck) was used for column chroma-
tography. Compounds 1a–1c were obtained according to the
published methods.29 Other reagents were commercially
available. Melting points were recorded on an Electrother-
mal type-9100 melting-point apparatus and are uncorrected.
The IR spectra were obtained on a 4300 Shimadzu spec-
3-Ethyl-8-phenyl-3H-imidazo[4’,5’:3,4]benzo[c]isoxazole (3a)
Compound 3a was obtained as colourless needles (EtOH).
Yield (75%); mp 99–101 8C. 1H NMR (CDCl3) d: 1.56 (t, J =
7.0 Hz, 3H), 4.25 (q, J = 7.0 Hz, 2H), 7.44–7.66 (m, 5H), 7.88
Published by NRC Research Press

726
Can. J. Chem. Vol. 87, 2009
(s, 1H), 8.88 (dd, J = 8.0 Hz, J’ = 2.0 Hz, 2H). MS (m/z): 263
(M+). Anal. calcd. for C16H13N3O (263.3): C, 72.99; H, 4.98;
N, 15.96. Found: C, 72.75; H, 4.83; N, 15.88.
C19H19N3O2 (321.4): C, 71.01; H, 5.96; N, 13.08. Found: C,
70.75; H, 5.82; N, 13.45.
Synthesis of o-amino-ketones (4a–4g)
8-(4-Chlorophenyl)-3-ethyl-3H-
imidazo[4’,5’:3,4]benzo[c]isoxazole (3b)
General procedure
Zinc dust (1 g, 15.3 mmol) was added with stirring over 5
h period to a solution of 3a–3g (4 mmol) in EtOH (30 mL)
and 20% NaOH (20 mL). After the addition was completed,
the mixture was refluxed for 1 h and then poured into water.
The product was extracted with CHCl3 (2 Â 30 mL). The
extract was washed with water (2 Â 30 mL), and then it
was dried and evaporated to give pure 4a–4g.
Compound 3b was obtained as colourless needles (EtOH).
Yield (77%); mp 186–188 8C. 1H NMR (CDCl3) d: 1.59 (t, J =
7.0 Hz, 3H), 4.27 (q, J = 7.0 Hz, 2H), 7.43 (d, J = 9.5 Hz, 1H),
7.59 (d, J = 9.5 Hz, 1H), 7.65 (d, J = 8.6 Hz, 2H), 7.89 (s, 1H),
8.91 (d, J = 8.6 Hz, 2H). MS (m/z): 299 (M+ + 2). Anal. calcd.
for C16H12ClN3O (297.7): C, 64.54; H, 4.06; N, 14.11. Found:
C, 64.34; H, 3.97; N, 13.86.
(5-Amino-1-ethyl-1H-benzo[d]imidazol-4-
yl)(phenyl)methanone (4a)
3-Ethyl-8-(4-methoxyphenyl)-3H-
imidazo[4’,5’:3,4]benzo[c]isoxazole (3c)
Compound 4a was obtained as colourless needles. Yield
(89%); mp 185–187 8C. IR (KBr): 3315 cm–1 (NH2),
1635 cm–1 (C=O).1H NMR (CDCl3) d: 1.51 (t, J = 7.3 Hz,
3H), 3.75 (br s, 2H), 4.13 (q, J = 7.3 Hz, 2H), 6.67 (d, J =
8.5 Hz, 1H), 7.09 (d, J = 8.5 Hz, 1H), 7.19–7.60 (m, 5H),
7.78 (s, 1H). MS (m/z) 265 (M+). Anal. calcd. for
C16H15N3O (265.3): C, 72.43; H, 5.70; N, 15.84. Found: C,
72.21; H, 5.65; N, 15.76.
Compound 3c was obtained as colourless needles (EtOH).
Yield (76%); mp 173–174 8C. 1H NMR (CDCl3) d: 1.62 (t, J =
7.3 Hz, 3H), 3.89 (s, 3H), 4.28 (q, J = 7.3 Hz, 2H), 7.17 (d, J =
9.0 Hz, 2H), 7.38 (d, J = 9.5 Hz, 1H), 7.55 (d, J = 9.5 Hz, 1H),
7.88 (s, 1H), 8.84 (d, J = 9.0 Hz, 2H). MS (m/z): 293 (M+).
Anal. calcd. for C17H15N3O2 (293.3): C, 69.61; H, 5.15; N,
14.33. Found: C, 69.55; H, 5.12; N, 14.44.
8-Phenyl-3-propyl-3H-imidazo[4’,5’:3,4]benzo[c]isoxazole (3d)
Compound 3d was obtained as colourless needles (EtOH).
Yield (73%); mp 119–122 8C. 1H NMR (CDCl3) d: 0.99 (t, J =
7.0 Hz, 3H), 1.77–2.12 (m, 2H), 4.21 (t, J = 7.0 Hz, 2H), 7.47–
7.69 (m, 5H), 7.89 (s, 1H), 8.89 (dd, J = 8.0 Hz, J’ = 2.0 Hz,
2H). MS (m/z): 277 (M+). Anal. calcd. for C17H15N3O (277.3):
C, 73.63; H, 5.45; N, 15.15. Found: C, 73.87; H, 5.51; N,
15.47.
(5-Amino-1-ethyl-1H-benzo[d]imidazol-4-yl)(4-
chlorophenyl)methanone (4b)
Compound 4b was obtained as colourless needles. Yield
(86%); mp 174–176 8C. IR (KBr): 3320 cm–1 (NH2),
1635 cm–1 (C=O).1H NMR (CDCl3) d: 1.51 (t, J = 7.3 Hz,
3H), 3.86 (br s, 2H), 4.12 (q, J = 7.3 Hz, 2H), 6.63 (d, J =
8.5 Hz, 1H), 7.11 (d, J = 8.5 Hz, 1H), 7.22 (d, J = 10.5 Hz,
2H), 7.42 (d, J = 10.5 Hz, 2H), 7.77 (s, 1H). MS (m/z): 301
(M+ + 2). Anal. calcd. for C16H14ClN3O (299.8): C, 64.11;
H, 4.71; N, 14.02. Found: C, 63.96; H, 4.61; N, 13.83.
8-(4-Chlorophenyl)-3-propyl-3H-
imidazo[4’,5’:3,4]benzo[c]isoxazole (3e)
Compound 3e was obtained as colourless needles (EtOH).
Yield (67%); mp 158–160 8C. 1H NMR (CDCl3) d: 1.05 (t, J =
7.3 Hz, 3H), 1.85–2.21 (m, 2H), 4.18 (t, J = 7.3 Hz, 2H), 7.40
(d, J = 9.5 Hz, 1H), 7.56 (d, J = 9.5 Hz, 1H), 7.62 (d, J =
8.6 Hz, 2H), 7.86 (s, 1H), 8.89 (d, J = 8.6 Hz, 2H). MS (m/z):
313 (M+ + 2). Anal. calcd. for C17H14ClN3O (311.8): C, 65.49;
H, 4.53; N, 13.48. Found: C, 65.25; H, 4.41; N, 13.55.
(5-Amino-1-ethyl-1H-benzo[d]imidazol-4-yl)(4-
methoxyphenyl)methanone (4c)
Compound 4c was obtained as colourless needles. Yield
(81%); mp 142–144 8C. IR (KBr): 3320 cm–1 (NH2),
1
1635 cm–1 (C=O). H NMR (CDCl3) d: 1.50 (t, J = 7.3 Hz,
3H), 3.74 (s, 3H), 4.13 (q, J = 7.3 Hz, 2H), 4.16 (br s, 2H),
6.65 (d, J = 8.5 Hz, 1H), 6.78 (d, J = 10.0 Hz, 2H), 7.09 (d,
J = 8.5 Hz, 1H), 7.36 (d, J = 10.0 Hz, 2H), 7.77 (s, 1H). MS
(m/z): 295 (M+). Anal. calcd. for C17H17N3O2 (295.3): C,
69.14; H, 5.80; N, 14.23. Found: C, 68.83; H, 5.71; N,
13.99.
8-(4-Methoxyphenyl)-3-propyl-3H-
imidazo[4’,5’:3,4]benzo[c]isoxazole (3f)
Compound 3f was obtained as colourless needles (EtOH).
Yield (77%); mp 155–157 8C. 1H NMR (CDCl3) d: 0.97 (t, J =
7.3 Hz, 3H), 1.83–2.19 (m, 2H), 3.90 (s, 3H), 4.17 (t, J =
7.3 Hz, 2H), 7.12 (d, J = 9.0 Hz, 2H), 7.40 (d, J = 9.5 Hz, 1H),
7.57 (d, J = 9.5 Hz, 1H), 7.85 (s, 1H), 8.85 (d, J = 9.0 Hz, 2H).
MS (m/z): 307 (M+). Anal. calcd. for C18H17N3O2 (307.3): C,
70.34; H, 5.58; N, 13.67. Found: C, 70.25; H, 5.62; N, 13.55.
(5-Amino-1-propyl-1H-benzo[d]imidazol-4-
yl)(phenyl)methanone (4d)
Compound 4d was obtained as colourless needles. Yield
(89%); mp 168–169 8C. IR (KBr): 3315 cm–1 (NH2),
1
1635 cm–1 (C=O). H NMR (CDCl3) d: 0.94 (t, J = 7.5 Hz,
3H), 1.75–2.10 (m, 2H), 4.04 (t, J = 7.5 Hz, 2H), 4.12 (br s,
2H), 6.62 (d, J = 8.5 Hz, 1H), 7.03 (d, J = 8.5 Hz, 1H),
7.11–7.52 (m, 5H), 7.75 (s, 1H). MS (m/z): 279 (M+). Anal.
calcd. for C17H17N3O (279.3): C, 73.10; H, 6.13; N, 15.04.
Found: C, 72.86; H, 6.01; N, 14.83.
3-Butyl-8-(4-methoxyphenyl)-3H-
imidazo[4’,5’:3,4]benzo[c]isoxazole (3g)
Compound 3g was obtained as colourless needles (EtOH).
Yield (83%); mp 139–141 8C. 1H NMR (CDCl3) d: 0.98 (t, J =
7.0 Hz, 3H), 1.23–1.58 (m, 2H), 1.82–2.10 (m, 2H), 3.90 (s,
3H), 4.18 (t, J = 7.0 Hz, 2H), 7.11 (d, J = 9.0 Hz, 2H), 7.39 (d,
J = 9.5 Hz, 1H), 7.57 (d, J = 9.5 Hz, 1H), 7.87 (s, 1H), 8.84 (d,
J = 9.0 Hz, 2H). MS (m/z): 321 (M+). Anal. calcd. for
(5-Amino-1-propyl-1H-benzo[d]imidazol-4-yl)(4-
chlorophenyl)methanone (4e)
Compound 4e was obtained as colourless needles. Yield
Published by NRC Research Press

Rahimizadeh et al.
727
(87%); mp 150–152 8C. IR (KBr): 3315 cm–1 (NH2),
7.1 Hz, 2H), 7.38 (dd, J = 9.0 Hz, J’ = 2.1 Hz, 1H), 7.58
(d, J = 9.0 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H), 8.12 (d, J =
2.1 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.02 (s, 1H). MS (m/z):
284 (M+ + 2). Anal. calcd. for C16H11ClN2O (282.7): C,
67.97; H, 3.92; N, 9.91. Found: C, 67.65; H, 3.81; N, 9.70.
1
1635 cm–1 (C=O). H NMR (CDCl3) d: 0.94 (t, J = 7.4 Hz,
3H), 1.67–2.05 (m, 2H), 3.76 (br s, 2H), 4.05 (t, J = 7.4 Hz,
2H), 6.66 (d, J = 8.5 Hz, 1H), 7.13 (d, J = 8.5 Hz, 1H), 7.21
(d, J = 9.0 Hz, 2H), 7.41 (d, J = 9.0 Hz, 2H), 7.75 (s, 1H).
MS (m/z): 315 (M+ + 2). Anal. calcd. for C17H16ClN3O
(313.8): C, 65.07; H, 5.14; N, 13.39. Found: C, 64.89; H,
5.03; N, 13.20.
3-Ethyl-7-methoxy-3,10-dihydrofluoreno[1,2-d]imidazol-10-
one (5c)
Compound 5c was passed through silica-gel column
(CHCl3/MeOH 20:1) to give 5c as yellow crystals. Yield
(5-Amino-1-propyl-1H-benzo[d]imidazol-4-yl)(4-
methoxyphenyl)methanone (4f)
1
(69%); mp 165–167 8C. IR (KBr): 1660 cm–1 (C=O). H
Compound 4f was obtained as colourless needles. Yield
NMR (CDCl3) d: 1.56 (t, J = 7.3 Hz, 3H), 3.90 (s, 3H), 4.23
(q, J = 7.3 Hz, 2H), 6.64 (dd, J = 8.1 Hz, J’ = 2.1 Hz, 1H),
7.03 (d, J = 2.1 Hz, 1H), 7.40 (d, J = 8.6 Hz, 1H), 7.49 (d, J =
8.6 Hz, 1H), 7.66 (d, J = 8.1 Hz, 1H), 8.01 (s, 1H). MS (m/z):
278 (M+). Anal. calcd. for C17H14N2O2 (278.3): C, 73.37; H,
5.07; N, 10.07. Found: C, 73.56; H, 5.21; N, 9.83.
(87%); mp 122–124 8C. IR (KBr): 3315 cm–1 (NH2),
1
1635 cm–1 (C=O). H NMR (CDCl3) d: 1.11 (t, J = 7.3 Hz,
3H), 1.87–2.23 (m, 2H), 3.92 (s, 3H), 4.22 (t, J = 7.3 Hz,
2H), 4.25 (br s, 2H), 6.79 (d, J = 8.5 Hz, 1H), 6.92 (d, J =
9.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 1H), 7.51 (d, J = 9.5 Hz,
2H), 7.91 (s, 1H). MS (m/z): 309 (M+). Anal. calcd. for
C18H19N3O2 (309.4): C, 69.88; H, 6.19; N, 13.58. Found: C,
69.69; H, 6.02; N, 13.41.
3-Propyl-3,10-dihydrofluoreno[1,2-d]imidazol-10-one (5d)
Compound 5d was passed through silica-gel column
(CHCl3/MeOH 30:1) to give 5d as yellow crystals. Yield
1
(41%); mp 135–137 8C. IR (KBr): 1660 cm–1 (C=O). H
(5-Amino-1-butyl-1H-benzo[d]imidazol-4-yl)(4-
methoxyphenyl)methanone (4g)
NMR (CDCl3) d: 0.97 (t, J = 7.3 Hz, 3H), 1.77–2.12 (m, 2H),
4.13 (t, J = 7.3 Hz, 2H), 7.08–7.54 (m, 5H), 7.65 (d, J =
9.0 Hz, 1H), 8.00 (s, 1H). MS (m/z): 262 (M+). Anal. calcd.
for C17H14N2O (262.3): C, 77.84; H, 5.38; N, 10.68. Found:
C, 78.05; H, 5.41; N, 10.50.
Compound 4g was obtained as colourless needles. Yield
(81%), mp 142–143 8C. IR (KBr): 3315 cm–1 (NH2),
1635 cm–1 (C=O).1H NMR (CDCl3) d: 1.11 (t, J = 7.0 Hz,
3H), 1.31–1.69 (m, 2H), 1.81–2.11 (m, 2H), 3.91 (s, 3H),
4.23 (t, J = 7.0 Hz, 2H), 4.27 (br s, 2H), 6.78 (d, J =
8.5 Hz, 1H), 6.93 (d, J = 9.5 Hz, 2H), 7.24 (d, J = 8.5 Hz,
1H), 7.52 (d, J = 9.5 Hz, 2H), 7.91 (s, 1H). MS (m/z): 323
(M+). Anal. calcd. for C19H21N3O2 (323.4): C, 70.57; H,
6.54; N, 12.99. Found: C, 70.44; H, 6.41; N, 12.86.
7-Chloro-3-propyl-3,10-dihydrofluoreno[1,2-d]imidazol-10-
one (5e)
Compound 5e was passed through silica-gel column
(CHCl3/MeOH 30:1) to give 5e as yellow crystals. Yield
(47%); mp 159–161 8C. IR (KBr): 1660 cm–1 (C=O).1H
NMR (CDCl3) d: 1.01 (t, J = 7.3 Hz, 3H), 1.77–2.15 (m,
2H), 4.22 (t, J = 7.3 Hz, 2H), 7.43 (dd, J = 9.0 Hz, J’ =
2.1 Hz, 1H), 7.56 (d, J = 9.0 Hz, 1H), 8.03 (d, J = 8.4 Hz,
1H), 8.12 (d, J = 2.1 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.02
(s, 1H). MS (m/z): 298 (M+ + 2). Anal. calcd. for
C17H13ClN2O (296.8): C, 68.81; H, 4.42; N, 9.44. Found: C,
68.60; H, 4.31; N, 9.31.
Synthesis of fluoreno[1,2-d]imidazol-10-one (5a–5g)
General procedure
To a solution of 4a–4f (2 mmol) in 3 N HCl (4 mL)
maintained at 0–5 8C, a solution of sodium nitrite (0.2 g,
6 mmol) in water (2 mL) was added with stirring over a
5 min period. After the addition was completed, the mixture
was stirred at 0–5 8C for 15 min, and then it was maintained
at 70 8C in a water bath for 4 h. After pouring this mixture
into crushed ice and water (50 mL), the precipitated solid
was removed by filtration, washed with water, and dried to
give crude 5a–5f.
7-Methoxy-3-propyl-3,10-dihydrofluoreno[1,2-d]imidazol-
10-one (5f)
Compound 5f was passed through silica-gel column
(CHCl3/MeOH 30:1) to give 5f as yellow crystals. Yield
1
(71%); mp 140–142 8C. IR (KBr): 1660 cm–1 (C=O). H
3-Ethyl-3,10-dihydrofluoreno[1,2-d]imidazol-10-one (5a)
Compound 5a was passed through silica-gel column
(CHCl3/MeOH 30:1) to give 5a as yellow crystals. Yield
(45%); mp 160–162 8C. IR (KBr): 1660 cm–1 (C=O).1H
NMR (CDCl3) d: 1.56 (t, J = 7.2 Hz, 3H), 4.24 (q, J =
7.2 Hz, 2H), 7.09–7.55 (m, 5H), 7.63 (d, J = 9.0 Hz, 1H),
8.01 (s, 1H). MS (m/z): 248 (M+). Anal. calcd. for
C16H12N2O (248.3): C, 77.40; H, 4.87; N, 11.28. Found: C,
77.23; H, 4.73; N, 11.12.
NMR (CDCl3) d: 0.98 (t, J = 7.2 Hz, 3H), 1.77–2.13 (m,
2H), 3.91 (s, 3H), 4.14 (t, J = 7.2 Hz, 2H), 6.66 (dd, J =
8.1 Hz, J’ = 2.1 Hz, 1H), 6.98 (d, J = 2.1 Hz, 1H), 7.38 (d,
J = 8.6 Hz, 1H), 7.47 (d, J = 8.6 Hz, 1H), 7.62 (d, J =
8.1 Hz, 1H), 8.03 (s, 1H). MS (m/z): 292 (M+). Anal. calcd.
for C18H16N2O2 (292.3): C, 73.95; H, 5.52; N, 9.58. Found:
C, 74.12; H, 5.69; N, 9.31.
3-Butyl-7-methoxy-3,10-dihydrofluoreno[1,2-d]imidazol-10-
one (5g)
7-Chloro-3-ethyl-3,10-dihydrofluoreno[1,2-d]imidazol-10-
one (5b)
Compound 5g was passed through silica-gel column
(CHCl3/MeOH 30:1) to give 5g as yellow crystals. Yield
1
Compound 5b was passed through silica-gel column
(CHCl3/MeOH 20: 1) to give 5b as yellow crystals. Yield
(67%); mp 120–122 8C. IR (KBr): 1660 cm–1 (C=O). H
NMR (CDCl3) d: 0.91 (t, J = 7.0 Hz, 3H), 1.15–1.55 (m,
2H), 1.71–2.01 (m, 2H), 3.88 (s, 3H), 4.14 (t, J = 7.0 Hz,
2H), 6.65 (dd, J = 8.1 Hz, J’ = 2.1 Hz, 1H), 6.96 (d, J =
1
(47%); mp 170–172 8C. IR (KBr): 1660 cm–1 (C=O). H
NMR (CDCl3) d: 1.50 (t, J = 7.1 Hz, 3H), 4.12 (q, J =
Published by NRC Research Press

728
Can. J. Chem. Vol. 87, 2009
(15) Yu, Z.; Velasco, D. Tetrahedron Lett. 1999, 40 (16), 3229–
3232. doi:10.1016/S0040-4039(99)00370-6.
(16) Danheiser, R. L.; Gould, A. E.; de la Pradilla, R. F.; Helga-
son, A. L. J. Org. Chem. 1994, 59 (19), 5514–5515. doi:10.
1021/jo00098a002.
2.1 Hz, 1H), 7.39 (d, J = 8.6 Hz, 1H), 7.46 (d, J = 8.6 Hz,
1H), 7.66 (d, J = 8.1 Hz, 1H), 7.98 (s, 1H). MS (m/z): 306
(M+). Anal. calcd. for C19H18N2O2 (306.4): C, 74.49; H,
5.92; N, 9.14. Found: C, 74.21; H, 5.79; N, 8.86.
(17) Hashemi, M.; Beni, Y. J. Chem. Res. Synop. 1999, (7): 434–
435. doi:10.1039/a807641c.
References
`
(1) Alcaro, S.; Arena, A.; Di Bella, R.; Neri, S.; Ottana, R.;
(18) Fu, J.-M.; Zhao, B.-P.; Sharp, M. J.; Snieckus, V. J. Org.
Chem. 1991, 56 (5), 1683–1685. doi:10.1021/jo00005a004.
(19) McCubbin, J. A.; Tong, X.; Wang, R.; Zhao, Y.; Snieckus,
V.; Lemieux, R. P. J. Am. Chem. Soc. 2004, 126 (4), 1161–
1167. doi:10.1021/ja038920f. PMID:14746485.
(20) Campo, M. A.; Larock, R. C. J. Org. Chem. 2002, 67 (16),
5616–5620. doi:10.1021/jo020140m. PMID:12153259.
(21) Yawer, M. A.; Hussain, I.; Reim, S.; Ahmed, Z.; Ullah, E.;
Ortuso, F.; Pavone, B.; Trincone, A.; Vigorita, M. G. Bioorg.
Med. Chem. 2005, 13 (10), 3371–3378. doi:10.1016/j.bmc.
2005.03.016. PMID:15848749.
(2) Lyakhov, S. A.; Lyakhova, E. A.; Karpenko, A. S.; Mal’tsev,
G. V.; Vel’cheva, I. V.; Litvinova, L. A.; Lebedyuk, M. N.;
Khorokhorina, G. A.; Fedchuk, V. P. Pharm. Chem. J. 2004,
38 (3), 128–131. doi:10.1023/B:PHAC.0000034300.89484.
b1.
(3) Sill, A. D.; Albrecht, W. L.; Andrews, E. R.; Fleming, R.
W.; Horgan, S. W.; Roberts, E. M.; Sweet, F. W. J. Med.
Chem. 1973, 16 (3), 240–245. doi:10.1021/jm00261a016.
PMID:4354693.
(4) Samanta, S.; Pain, A.; Ghosh, M.; Dutta, S.; Sanyal, U. Exp.
Oncol. 2005, 27 (4), 279–285. PMID:16404347.
(5) Perry, P. J.; Read, M. A.; Davies, R. T.; Gowan, S. M.;
Reszka, A. P.; Wood, A. A.; Kelland, L. R.; Neidle, S. J.
Med. Chem. 1999, 42 (14), 2679–2684. doi:10.1021/
jm990084q. PMID:10411488.
(6) Koyama, H.; Kamikawa, T. Tetrahedron Lett. 1997, 38 (22),
3973–3976. doi:10.1016/S0040-4039(97)00793-4.
(7) Gould, S. J.; Melville, C. R.; Cone, M. C.; Chen, J.; Carney,
J. R. J. Org. Chem. 1997, 62 (2), 320–324. doi:10.1021/
jo961486y. PMID:11671405.
(8) Enoch, I. V. M. V.; Swaminathan, M. J. Fluoresc. 2006,
16 (4), 501–510. doi:10.1007/s10895-006-0074-z. PMID:
16794872.
(9) Nie, G.; Cai, T.; Qu, L.; Xu, J.; Wei, Q.; Zhang, S. J. Elec-
troanal. Chem. 2008, 612 (2), 191–200. doi:10.1016/j.
jelechem.2007.09.025.
(10) Kono, S.; Sinananwanich, W.; Shibasaki, Y.; Ando, S.;
Ueda, M. Polym. J. 2007, 39 (11), 1150–1156. doi:10.1295/
polymj.PJ2007090.
(11) Yang, G.-Z.; Wu, M.; Lu, S.; Wang, M.; Liu, T.; Huang, W.
Polymer (Guildf.) 2006, 47 (13), 4816–4823. doi:10.1016/j.
polymer.2006.04.056.
¨
Iqbal, I.; Fischer, C.; Reinke, H.; Gorls, H.; Langer,
P. Tetrahedron 2007, 63 (51), 12562–12575. doi:10.1016/j.
tet.2007.10.027.
(22) Tu, S.; Jiang, B.; Jiang, H.; Zhang, Y.; Jia, R.; Zhang, J.;
Shao, Q.; Li, C.; Zhou, D.; Cao, L. Tetrahedron 2007, 63
(25), 5406–5414. doi:10.1016/j.tet.2007.04.053.
(23) Fillion, E.; Dumas, A. M.; Hogg, S. A. J. Org. Chem. 2006,
71 (26), 9899–9902. doi:10.1021/jo0618876. PMID:
17168619.
(24) DeTar, D. F.; Relyea, D. I. J. Am. Chem. Soc. 1954, 76 (6),
1680–1685. doi:10.1021/ja01635a066.
(25) (a) Bakavoli, M.; Feizyzadeh, B.; Rahimizadeh, M. Tetrahe-
dron Lett. 2006, 47 (50), 8965–8968. doi:10.1016/j.tetlet.
2006.10.037.; (b) Bakavoli, M.; Nikpour, M.; Rahimizadeh,
M. J. Heterocycl. Chem. 2006, 43 (5), 1327–1329. doi:10.
1002/jhet.5570430527.; (c) Bakavoli, M.; Davoodnia, A.;
Vahedinia, A.; Rahimizadeh, M.; Roshani, M. Heterocycles
2006, 68 (4), 801. doi:10.3987/COM-06-10669.; (d) Baka-
voli, M.; Bakavoli, M.; Davoodnia, A.; Heravi, M. M.;
Rahimizadeh, M.; Heravi, M. M. Mendeleev Commun. 2006,
16 (1), 29. doi:10.1070/MC2006v016n01ABEH002177.;
(e) Bakavoli, M.; Nikpour, M.; Rahimizadeh, M.; Saberi, M.
R.; Sadeghian, H. Bioorg. Med. Chem. 2007, 15 (5), 2120–
2126. doi:10.1016/j.bmc.2006.12.022. PMID:17210254.;
(f) Bakavoli, M.; Pordel, M.; Rahimizadeh, M.; Jahandari,
P.; Rezaei Seresht, E. Heterocycles 2008, 75 (1), 165.
doi:10.3987/COM-07-11148.
(26) Davis, R. B.; Pizzini, L. C. J. Org. Chem. 1960, 25 (11),
1884–1888. doi:10.1021/jo01081a015.
(27) Simpson, J. C. E.; Stephenson, O. J. Chem. Soc. 1942, 353.
doi:10.1039/jr9420000353.
(12) Uckert, F.; Setayesh, S.; Mullen, K. Macromolecules 1999,
32 (14), 4519–4524. doi:10.1021/ma990157f.
(13) Lemmer, U.; Heun, S.; Mahrt, R.; Scherf, U.; Hopmeier, M.;
Siegner, U.; Gobel, E.; Mullen, K.; Bassler, H. Chem. Phys.
Lett. 1995, 240 (4), 373–378. doi:10.1016/0009-2614(95)
00512-3.
(28) Pechenia, V. M.; Mukhina, N. A.; Klimenko, V. G.; Granik,
V. G. Chem. Heterocycl. Compd. 1986, 8, 1082.
(29) Aliprandi, B.; Cacace, F.; Possagno, E. Ann. Chim. (Italy)
1958, 48, 1349.
(14) Olah, G. A.; Mathew, T.; Farnia, M.; Prakash, S. Synlett
1999, 1999 (7), 1067–1068. doi:10.1055/s-1999-2770.
Published by NRC Research Press