Preparation of Pyrido[2,3-b]indole Derivatives Using Silicates of Group 1 and 2 Metals

Article abstract of DOI:10.1002/jhet.3284

An efficient synthesis of 2,4-diaryl-9H-pyrido[2,3-b] indole derivatives in aqueous medium via the three-component reaction of indolin-2-one, a chalcone and ammonium acetate was developed using Na₂SiO₃, K₂SiO₃, Li₂SiO₃, CaSiO₃, MgSiO₃, BaSiO₃, SrSiO₃, and ZnSiO₃ as catalysts. Results of activity evaluations indicated that among of the metal silicate used alkali metal silicates exhibits much higher activity than other samples due to the stronger basicity power and higher solubility in water. Under the optimum reaction conditions, all of the reactions with diverse aromatic aldehydes provided high yields in low reaction times.

Full text of DOI:10.1002/jhet.3284

Month 2018 Preparation of Pyrido[2,3-b]indole Derivatives Using Silicates of Group 1
and 2 Metals
a
b
*
Setareh Sheikh and Abbas Fazlinia
aDepartment of Chemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran
bDepartment of Chemistry, Zarghan Branch, Islamic Azad University, Zarghan, Iran
*E-mail: fazliniaabbas@gmail.com
Received April 17, 2018
DOI 10.1002/jhet.3284
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
An efficient synthesis of 2,4-diaryl-9H-pyrido[2,3-b] indole derivatives in aqueous medium via the
three-component reaction of indolin-2-one, a chalcone and ammonium acetate was developed using
Na2SiO3, K2SiO3, Li2SiO3, CaSiO3, MgSiO3, BaSiO3, SrSiO3, and ZnSiO3 as catalysts. Results of activ-
ity evaluations indicated that among of the metal silicate used alkali metal silicates exhibits much higher
activity than other samples due to the stronger basicity power and higher solubility in water. Under the
optimum reaction conditions, all of the reactions with diverse aromatic aldehydes provided high yields in
low reaction times.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
[9,13–17]. Some of these methods require multistep routes
of synthesis, long reaction time, and costly substrates.
Recently, pyrido[2,3-b] indole derivatives have been
prepared via new strategies including the reaction of
indolin-2-one, a chalcone and ammonium acetate [18],
cyclizations of indolylchalcone oxime ester [19], and the
tandem reaction of acyl chlorides, terminal alkynes, and
2-aminoindole hydrochlorides [20]. The drawback of
these strategies is the need for strongly basic conditions,
which could be eliminated by further development of the
synthetic procedures.
Metal silicates such as Na2SiO3 are milder basic catalysts
compared to NaOH and KOH that have been used
effectively for various reactions [21]. The low cost,
stability, and safety of metal silicates make them as
interesting candidates for use as bionanocomposites,
fillers, strong basic catalysts, inorganic phosphors, and
adsorbent materials. The negative surface charge of
metal silicates helps us to adsorb heavy metal cations
effectively from wastewaters. Alkali silicates are not toxic
and were used widely as raw materials in foundry
industries including ceramics, glasses, cement, and molds.
Due to lack of toxicity, they can also be used as
corrosion inhibitors, cleaning materials, or ceramic paint
components. Herein, we aimed to start new work on the
use of selected metal silicates as efficient catalysts for the
preparation of some heterocyclic compounds [22–24].
Thus, as part of our ongoing work to develop new
strategies for the preparation of heterocyclic compounds
[25–30], herein we report a metal silicate catalyzed the
The common occurrence of nitrogen-containing
heterocycles in natural and synthetic drugs has motivated
many efforts to synthesize pyrimidines, quinolines, and
indolines exhibiting a wide range of essential biological
functions. In particular, fused heterocycles such as
pyranoquinolines, thienopyridines, and pyranopyrimidines
have attracted considerable interest [1–6].
Carbolines, a group of fused N-heterocycles composed
of indoline and pyridine cores, are found in many
natural and medicinal products. A significant number of
carbolines have been exploited for diverse pharmaceutical
applications. Some γ-carbolinium salts are found to be
potent inhibitors of cholinesterases, N-methyl-D-aspartate
receptors, and monoamine oxidases [7]. Harmine, a β-
carboline, has been identified as an inhibitor of DYRK
family of kinases [8]. The α-carboline (pyrido[2,3-b]
indole) structure is present in some natural products
that show cytotoxic and anticancer activity, as well as
effects on central nervous system [9]. In general,
carbolines have a potential for a broad range of biological
effects including antitumor, antimalarial, antiproliferative,
antifungal, and antibacterial activities [10–12].
The previously used routes for the synthesis of
pyrido[2,3-b] indole derivatives are based on the annulation
of azaindoles, DielsÀAlder reaction, annulation of indoles,
VilsmeierÀHaack reaction, palladium-catalyzed reactions
of 2-amidinylindole-3-carbaldehyde with acetophenones,
and 6π-electrocyclization of indole-3-alkenyl oximes
© 2018 Wiley Periodicals, Inc.

S. Sheikh and A. Fazlinia
Vol 000
Table 2
three-component synthesis of 2,4-diaryl-9H-pyrido[2,3-b]
indoles based on the reaction of indolin-2-one, a chalcone
and ammonium acetate (Scheme 1).
Preparation of 2,4-diphenyl-9H-pyrido[2,3-b] indole using different metal
silicates.
Catalyst (40 mol%)
Time (h)
Yield (%)a
Li2SiO3
Na2SiO3
K2SiO3
BaSiO3
MgSiO3
CaSiO3
SrSiO3
2
2
2
5
5
5
7
7
93
90
91
80
87
77
78
82
RESULTS AND DISCUSSION
Initially, the sodium silicate catalyzed cyclocondensation
of benzaldehyde (1.0 mmol), chalcone, (1 mmol), and
indolin-2-one was performed with different solvents and
amounts of catalyst. The results are summarized in
Table 1. No product was formed in solvents with boiling
points below 70°C, namely, Et2O, CH2Cl2, and hexane.
Complex mixtures were obtained in polar aprotic solvents
including CH3CN and EtOAc, due to the participation of
solvents in reactions with starting materials and catalysts.
Finally, we found that protic solvents, for example, EtOH
and H2O, as well as solvent-free conditions, were suitable
for this transformation. The best yield was obtained in
water while using 40 mol% of the catalyst. The solvent-
free conditions gave lower product yield compared to the
use of EtOH and H2O.
ZnSiO3
H2O as solvent (reflux).
aIsolated yield.
results showed that alkali metal silicates are more reactive
than those of alkali earth metal silicates. All of these
catalysts provided complete conversion of the starting
materials. However, SrSiO3 and ZnSiO3 were less
reactive than others. The pH of selected metal silicates
was experimentally determined as follows: Na2SiO3
(pH = 12.3), K2SiO3 (pH = 12.8), Li2SiO3 (pH = 13.1),
CaSiO3 (pH = 9.2), MgSiO3 (pH = 10.2), BaSiO3
(pH = 8.9), SrSiO3 (pH = 8.3), and ZnSiO3 (pH = 7.9)
for a 1 M aqueous solution, and the results could justify
the reactivity of selected metal silicates.
Next, the effect of various metal silicates including
Na2SiO3, K2SiO3, Li2SiO3, CaSiO3, MgSiO3, BaSiO3,
SrSiO3, and ZnSiO3 in aqueous media and under
solvent-free conditions was investigated (Table 2). The
Following the optimization of reaction conditions,
several different aromatic aldehydes containing electron-
withdrawing Cl, Br, and NO2 substituents as well as
electron-donating groups (e.g., Me and OMe) were
tolerated, with the reaction giving high yields of the
desired products (Table 3, products 3a–p). In general, the
electronic nature of the substituents had little influence on
the product yields but considerably affected the reaction
duration. The presence of an electron-withdrawing
substituent on the aromatic ring of chalcone led to shorter
reaction times than in the case of chalcones with an
electron-donating substituent. Insertion of different
groups such as chlorine and nitro in the ortho-position of
the aromatic ring has an adverse effect on the reaction
rate and slow down the reaction progress due to steric
hindrance effects (Table 3). Encouraged by the above
results, the generality of the method was explored using
Li2SiO3, MgSiO3, and ZnSiO4 as catalysts (Table 3).
Noticeably, the results were similar to those obtained
with Na2SiO3. However, ZnSiO4 and BaSiO3 showed
less reactivity than Na2SiO3 and Li2SO4. The alkali metal
silicates are a stronger base than those of other metal
silicates. Thus, the reaction time is lower when Na2SiO3,
and Li2SiO3 was used. However, the product yields have
no distinctive differences. On the other hand, alkali metal
silicates have good solubility in water and thus can act as
a homogeneous catalytic system which shows higher
activity than those of non-soluble silicates such as ZnSiO4.
Scheme 1. Preparation of 2,4-diaryl-9H-pyrido[2,3-b] indole derivatives.
Table 1
Solvent selection for Na2SiO3-catalyzed preparation of 2,4-diphenyl-9H-
pyrido[2,3-b]indole.
Catalyst
(mol%)
Solvent
(5 mL)
Temperature
(°C)
Time
(h)
Yield
(%)a
40
40
40
40
40
40
40
80
20
30
Hexane
68
77
78
80
35
2
2
2
2
2
2
2
2
3
2
0
10b
35
15b
0
EtOAc
EtOH
CH3CN
Et2O
CH2Cl2
H2O
H2O
H2O
-
39
0
100
100
100
100
90
85
70
45b
aIsolated yield.
bComplex mixture.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Preparation of Pyrido[2,3-b]indole Derivatives
Table 3
Synthesis of 2,4-diaryl-9H-pyrido[2,3-b] indole derivatives using 40 mol% of metal silicates as catalyst (Scheme 1).
Na2SiO3 [time (h)/
yield (%)a]
Li2SiO3 [time (h)/
yield (%)a]
MgSiO3 [time (h)/
yield (%)a]
ZnSiO3 [time (h)/
yield (%)a]
Product
Ar
R
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
Ph
H
H
H
H
H
H
CH3
CH3
CH3
Cl
H
H
H
Br
NO2
OCH3
2/90
3/86
4/84
2/92
2/89
2/74
4/84
5/79
4/88
2/79
3/83
3/90
3/89
2/86
2/91
4/88
2/87
4/83
4/87
2/95
2/90
2/89
4/77
4/80
4/84
2/86
3/88
3/90
2/85
2/91
2/90
4/88
5/87
7/88
8/91
5/89
4/90
5/72
7/77
7/89
7/82
5/83
6/91
6/90
5/80
5/84
5/91
7/81
7/82
10/73
11/74
7/73
7/81
7/69
10/77
11/79
11/75
7/82
9/76
9/79
4-Methylphenyl
4-Methoxyphenyl
4-Chlorophenyl
4-Nitrophenyl
Furan-2-yl
Ph
4-Methylphenyl
4-tert-Butylphenyl
Ph
2-Chlorophenyl
2-Bromophenyl
2-Nitrophenyl
Ph
8/83
7/85
7/83
11/70
Ph
Ph
aIsolated yields.
The suggested reaction mechanism and the role of
catalyst are shown in Scheme 2. The reaction begins with
the formation of enolate (1) and imine (2) derivatives
of indolin-2-one and chalcones, respectively. The
condensation of (1) and (2) results in the intermediate (3),
which subsequently undergoes intramolecular reaction to
form the intermediate (4). The elimination of water from
intermediate 4 leads to the formation of dihydropyridine
5 that is easily oxidized and converted to the target
product 3a–p.
recrystallization from ethanol was sufficient for the
purification of the product.
EXPERIMENTAL
All reagents were purchased from Merck and Sigma-
Aldrich and were used without further purification. NMR
spectra were recorded on a Bruker Avance DPX 400
1
instrument (400 MHz for H nuclei, 100 MHz for 13C
In summary, metal silicates can be used as
environmentally safe catalysts for the synthesis of 2,4-
diaryl-9H-pyrido[2,3-b] indole derivatives in aqueous
media. Excellent yields of the products were achieved
in all cases. No complex procedures were required, and
use of toxic organic solvents was avoided as simple
nuclei) in DMSO-d6 relative to TMS (0.00 ppm).
Elemental analysis (CHN) was performed on a Heraeus
CHN-O RAPID elemental analyzer. Melting points were
determined in open capillaries with a Buchi B-510
melting point apparatus. TLC was performed on
Polygram SIL G/UV 254 silica gel plates.
Typical procedure.
Ammonium acetate (0.308 g,
4 mmol) was added to a stirred mixture of indolin-2-one
(0.133 g, 1 mmol), the appropriate chalcone (1.0 mmol),
and metal silicate (40 mol%) in water (10 mL) and the
mixture was refluxed for the time indicated in Table 3.
The reaction progress was monitored by TLC using
hexane/EtOAc (9/1) mobile phase. After completion of
the reaction, the mixture was cooled to 25°C, filtered,
washed with water, and finally the solid product was
Scheme 2. Proposed reaction mechanism.
purified by recrystallization from ethanol.
2,4-Diphenyl-9H-pyrido[2,3-b] indole (product 3a). Yield
0.288 g (90%), white solid, mp 218–220°C (mp 216.5–
1
217.5°C19). H NMR spectrum, δ, ppm (J, Hz): 6.53 (1H,
d, J = 8.2), 7.01 (1H, t, J = 7.6), 7.24 (d, J = 7.6, 1H),
7.44–7.53 (m, 8H), 7.77–7.80 (m, 2H), 8.25 (d, J = 7.2,
2H), 12.01 (s, 1H, NH). 13C NMR spectrum, δ, ppm:
111.7, 113.3, 115.5, 119.9, 120.9, 123.6, 126.9, 127.7,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Sheikh and A. Fazlinia
Vol 000
128.1, 128.4, 128.8, 129.0, 129.3, 139.1, 139.4, 140.7,
146.4, 153.6, 155.1. Found, %: C 86.14; H 4.97; N 8.68.
C23H16N2. Calculated, %: C 86.22; H 5.03; N 8.74
11.98 (s, 1H, NH). 13C NMR spectrum, δ, ppm: 110.7,
111.0, 111.2, 112.7, 119.2, 119.1, 120.7, 123.5, 126.9,
127.5, 128.8, 129.3, 133.9, 139.3, 140.7, 143.6, 146.6,
152.8, 154.6. Found: C, 81.29; H, 4.48; N, 8.96%
C21H14N2O. Calculated, %: C, 81.27; H, 4.55; N, 9.03%
(Table 2).
2-Phenyl-4-(p-tolyl)-9H-pyrido[2,3-b] indole (product 3b).
Yield 0.287 g (86%), white solid, mp 221–223°C (mp
(Table 2).
1
221–223°C20). H NMR spectrum, δ, ppm (J, Hz): 2.55
4-Phenyl-2-(p-tolyl)-9H-pyrido[2,3-b] indole (product 3g).
(s, 3H, CH3), 6.52 (d, J = 8.2, 1H), 7.01 (t, J = 7.5, 1H),
7.23 (d, J = 7.5, 1H), 7.45–7.56 (m, 6H), 7.72–7.74 (m,
3H), 8.23 (d, J = 7.1, 2H), 12.18 (s, 1H, NH); 13C NMR
spectrum, δ, ppm: 21.6, 111.7, 113.4, 116.1, 119.9,
121.4, 123.8, 126.8, 127.6, 128.4, 128.8, 129.0, 129.4,
136.7, 139.2, 140.5, 141.1, 146.7, 153.7, 155.1. Found:
C, 86.11; H, 5.37; N, 8.26% C24H18N2. Calculated, %:
C, 86.20; H, 5.43; N, 8.38% (Table 2).
Yield 0.280 g (84%), white solid, mp 255–257°C (mp
252–254°C19). 1H NMR spectrum, δ, ppm (J, Hz):
2.35 (s, 3H, CH3), 7.00 (d, J = 7.7, 1H), 7.30 (t, J = 8.0,
2H), 7.39 (t, J = 7.6, 1H), 7.49–7.64 (m, 6H), 7.74–7.76
(m, 2H), 8.14 (d, J = 8.0, 2H), 12.03 (s, 1H, NH);
13C NMR spectrum, δ, ppm: 21.2, 111.3, 112.1,
113.0, 119.4, 120.6, 122.6, 126.9, 127.4, 128.8,
128.9, 129.2, 129.5, 137.2, 138.7, 139.4, 139.9, 145.3,
152.8, 155.2. Found: C, 86.14; H, 5.36; N, 8.32%
C24H18N2. Calculated, %: C, 86.20; H, 5.43; N, 8.38%
4-(4-Methoxyphenyl)-2-phenyl-9H-pyrido[2,3-b]
(product 3c).
indole
Yield 0.294 g (84%), white solid, mp
227–229°C (mp 220–221°C18). 1H NMR spectrum, δ,
ppm (J, Hz): 4.01 (s, 3H, OCH3), 6.54 (d, J = 8.1, 1H),
7.00 (t, J = 7.6, 1H), 7.16 (d, J = 8.0, 2H), 7.21 (d,
J = 7.6, 1H), 7.47–7.58 (m, 4H), 7.72–7.76 (m, 3H), 8.17
(d, J = 7.1 Hz, 2H), 12.08 (s, 1H, NH). 13C NMR
spectrum, δ, ppm: 55.5, 111.2, 112.8, 114.5, 115.2,
119.9, 120.8, 122.7, 126.4, 127.7, 128.6, 129.3, 130.3,
131.9, 139.7, 140.4, 146.4, 153.5, 155.1, 159.8. Found:
C, 82.23; H, 5.14; N, 7.94% C24H18N2O. Calculated, %:
C, 82.26; H, 5.18; N, 7.99% (Table 2).
(Table 2).
2,4-Di-p-tolyl-9H-pyrido[2,3-b] indole (product 3h). Yield
0.275 g (79%), white solid, mp 247–249°C (mp 245–
247°C20). 1H NMR spectrum, δ, ppm (J, Hz): 2.37
(s, 3H, CH3), 2.54 (s, 3H, CH3), 6.86 (d, J = 8.0,
1H), 7.01 (d, J = 7.8, 1H), 7.23–7.42 (m, 5H), 7.54 (s,
1H), 7.64–7.71 (m, 3H), 8.11 (d, J = 8.0, 2H), 12.05
(s, 1H, NH); 13C NMR spectrum, δ, ppm: 21.2, 21.3,
111.5, 111.9, 113.0, 119.3, 120.2, 122.3, 126.9, 127.3,
128.8, 129.7, 129.9, 136.2, 137.0, 138.8, 139.0, 139.9,
145.7, 153.0, 153.9. Found: C, 86.11; H, 5.73; N,
7.97% C25H20N2. Calculated, %: C, 86.17; H, 5.79; N,
4-(4-Chlorophenyl)-2-phenyl-9H-pyrido[2,3-b]
(product 3d).
indole
Yield 0.326 g (92%), white solid, mp
236–238°C (mp 227–228°C18). 1H NMR spectrum, δ,
ppm (J, Hz): 6.55 (d, J = 8.1, 1H), 7.02 (t, J = 7.6, 1H),
7.23 (d, J = 7.6, 1H), 7.47–7.58 (m, 4H), 7.69 (d,
J = 7.1, 2H), 7.72 (s, 1H), 7.80 (d, J = 7.1, 2H), 8.28 (d,
J = 7.2, 2H), 12.08 (s, 1H, NH). 13C NMR spectrum, δ,
ppm: 111.3, 113.2, 118.9, 119.5, 121.7, 126.7, 127.3,
127.5, 128.1, 128.8, 128.9, 130.5, 133.6, 137.6, 139.1,
139.7, 143.7, 152.8, 153.4. Found: C, 77.85; H, 4.26; N,
7.89% C23H15ClN2. Calculated, %: C, 77.85; H, 4.26; N,
8.04% (Table 2).
4-(4-(tert-Butyl)phenyl)-2-(p-tolyl)-9H-pyrido[2,3-b] indole
(product 3i). Yield 0.343 g (88%), white solid, mp 255–
257°C (mp >250°C20). H NMR spectrum, δ, ppm (J,
1
Hz): 1.39 (s, 9H, C (CH3)3), 2.37 (s, 3H, CH3), 7.02 (d,
J = 7.6, 1H), 7.26–7.72 (m, 10H), 8.13 (d, J = 8.0, 2H),
12.01 (s, 1H, NH); 13C NMR spectrum, δ, ppm: 21.0,
31.3, 34.7, 111.8, 112.9, 119.3, 120.1, 121.8, 125.6,
126.4, 126.9, 128.5, 129.4, 136.1, 136.9, 138.6, 139.7,
145.5, 153.1, 153.9. Found: C, 86.18; H, 6.79; N, 7.11%
C28H26N2. Calculated, %: C, 86.12; H, 6.71; N, 7.17%
(Table 2).
7.89% (Table 2).
4-(4-Nitrophenyl)-2-phenyl-9H-pyrido[2,3-b] indole (product
3e). Yield 0.325 g (89%), white solid, mp 236–238°C.
1H NMR spectrum, δ, ppm (J, Hz): 6.53 (d, J = 8.1, 1H),
7.02 (t, J = 7.6, 1H), 7.24 (d, J = 7.6, 1H), 7.43–7.55 (m,
4H), 7.78–7.81 (m, 3H), 7.70 (d, J = 8.0, 2H), 8.27 (d,
J = 7.3, 2H), 12.15 (s, 1H, NH). 13C NMR spectrum, δ,
ppm: 111.6, 113.4, 119.9, 120.2, 121.7, 125.3, 126.8,
127.9, 128.5, 128.9, 129.2, 129.6, 137.6, 138.8, 139.4,
140.7, 143.7, 153.8, 155.2. Found: C, 75.53; H, 4.09; N,
11.46% C23H15N3O2. Calculated, %: C, 75.60; H, 4.14;
2-(4-Chlorophenyl)-4-phenyl-9H-pyrido[2,3-b]
(product 3j).
indole
Yield 0.280 g (79%), white solid, mp
272–274°C (mp 271–273°C19). 1H NMR spectrum, δ,
ppm (J, Hz): 7.04 (d, J = 7.6, 1H), 7.40–7.68 (m, 8H),
7.81 (d, J = 8.0, 2H), 8.21 (d, J = 8.0, 2H), 12.14
(s, 1H, NH); 13C NMR spectrum, δ, ppm: 111.8, 112.0,
113.5, 119.7, 120.1, 122.1, 127.0, 127.6, 129.1, 129.3,
129.4, 131.1, 134.2, 138.0, 139.7, 140.3, 144.5,
153.1, 153.7. Found: C, 77.93; H, 4.37; N, 7.80%
C23H15ClN2. Calculated, %: C, 77.85; H, 4.26; N, 7.89%
(Table 2).
N, 11.50% (Table 2).
4-(Furan-2-yl)-2-phenyl-9H-pyrido[2,3-b] indole (product
3f). Yield 0.229 g (74%), white solid, mp 175–177°C
1
(mp 174–175°C18). H NMR spectrum, δ, ppm (J, Hz):
4-(2-Chlorophenyl)-2-phenyl-9H-pyrido[2,3-b]
(product 3k).
243–244°C (mp 245–247°C19). 1H NMR spectrum, δ,
indole
6.58 (d, J = 8.0, 1H), 6.70 (d, J = 3.8, 1H), 7.15–7.59
(m, 6H), 7.77–7.81 (m, 3H), 8.23 (d, J = 7.3, 2H),
Yield 0.294 g (83%), white solid, mp
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Preparation of Pyrido[2,3-b]indole Derivatives
ppm (J, Hz): 7.04 (d, J = 7.6, 1H), 7.40–7.88 (m, 11H),
8.21–8.28 (m, 3H), 12.09 (s, 1H, NH); 13C NMR
spectrum, δ, ppm: 111.8, 112.3, 118.3, 119.7, 120.1,
123.3, 127.3, 127.5, 127.8, 128.6, 128.7, 128.8, 128.9,
130.6, 131.0, 134.1, 137.6, 139.8, 140.6, 153.1, 154.0.
Found: C, 77.96; H, 4.39; N, 7.68% C23H15ClN2.
Calculated, %: C, 77.85; H, 4.26; N, 7.89% (Table 2).
7.00 (d, J = 7.6, 1H), 7.14–7.76 (m, 10H), 8.18 (d,
J = 8.4, 1H), 11.74 (s, 1H, NH); 13C NMR spectrum, δ,
ppm: 55.8, 111.5, 112.3, 113.3, 114.6, 119.7, 121.3,
122.4, 126.3, 127.7, 128.7, 128.9, 129.2, 133.1, 138.6,
139.6, 146.4, 153.1, 154.0, 159.3. Found: C, 82.19; H,
5.11; N, 7.91% C24H18N2O. Calculated, %: C, 82.26; H,
5.18; N, 7.99% (Table 2).
4-(2-Bromophenyl)-2-phenyl-9H-pyrido[2,3-b]
(product 3l).
indole
Yield 0.358 g (90%), light brown solid,
1
mp 256–258°C (mp 254–255°C19). H NMR spectrum, δ,
ppm (J, Hz): 7.04 (d, J = 7.8, 1H), 7.37–7.66 (m, 10H),
7.83–7.86 (m, 2H), 8.25 (d, J = 8.0, 1H), 12.12 (s, 1H,
NH); 13C NMR spectrum, δ, ppm: 112.3, 118.2, 120.2,
120.7, 122.3, 123.3, 127.3, 127.5, 128.0, 128.6, 128.8,
129.1, 130.5, 130.9, 132.1, 133.6, 137.6, 139.4, 140.7,
153.3, 153.9. Found: C, 69.16; H, 3.74; N, 6.95%
C23H15BrN2. Calculated, %: C, 69.19; H, 3.79; N, 7.02%
(Table 2).
Acknowledgment. The authors are thankful to the Islamic Azad
University-Zarghan Branch research council for the partial
support of this investigation.
REFERENCES AND NOTES
[1] Ghashang, M.; Mansoor, S. S.; Mohammad Shafiee, M. R.;
Kargar, M.; Najafi Biregan, M.; Azimi, F.; Taghrir, H. J Sulfur Chem
2016, 37, 377.
[2] Ghashang, M.; Mansoor, S. S.; Shams-Solaree, L.; Sharifian-
esfahani, A. Iran J Catal 2016, 6, 237.
[3] Aswin, K.; Ghashang, M.; Mansoor, S. S. Iran J Catal 2015, 5,
175.
[4] Dehbashi, M.; Aliahmad, M.; Mohammad Shafiee, M. R.;
Ghashang, M. Synth React Inorg Metal-Org Nano-Metal Chem 2013,
43, 1301.
[5] Ghashang, M. Curr Org Synth 2012, 9, 727.
[6] Taghrir, H.; Ghashang, M.; Biregan, M. N. Chin Chem Lett
2016, 27, 119.
[7] Otto, R.; Penzis, R.; Gaube, F.; Adolph, O.; Föhr, K. J.;
Warncke, P.; Robaa, D.; Appenroth, D.; Fleck, C.; Enzensperger, C.;
Lehmann, J.; Winckler, T. J Med Chem 2015, 58, 6710.
[8] Gockler, N.; Jofre, G.; Papadopoulos, C.; Soppa, U.; Tejedor,
F. J.; Becker, W. FEBS J 2009, 276, 6324.
4-(2-Nitrophenyl)-2-phenyl-9H-pyrido[2,3-b] indole (product
3m).
Yield 0.325
g
(89%), yellow solid, mp
242–244°C (mp 238–239°C19). 1H NMR spectrum, δ,
ppm (J, Hz): 7.04 (d, J = 7.8, 1H), 7.31–7.57 (m, 5H),
7.68 (d, J = 7.6, 1H), 7.75 (t, J = 7.6, 1H), 7.53 (t,
J = 7.6, 1H), 8.21–8.25 (m, 3H), 12.16 (s, 1H, NH);
13C NMR spectrum, δ, ppm: 111.8, 113.0, 119.3,
120.2, 121.7, 124.3, 126.5, 127.3, 127.5, 127.9, 128.8,
129.1, 129.4, 130.6, 135.1, 137.6, 139.8, 140.7, 143.5,
153.1, 154.0. Found: C, 75.53; H, 4.02; N, 11.44%
C23H15N3O2. Calculated, %: C, 75.60; H, 4.14; N,
11.50% (Table 2).
[9] Wadsworth, A. D.; Naysmith, B. J.; Brimble, M. A. Eur J Med
Chem 2015, 97, 816.
2-(4-Bromophenyl)-4-phenyl-9H-pyrido[2,3-b]
indole
(product 3n).
Yield 0.335 g (86%), white solid, mp
[10] Davidson, H. M. Curr Atheroscler Rep 2007, 11, 67.
[11] Mineno, M.; Sera, M.; Ueda, T.; Mizufune, H.; Zanka, A.;
O’Bryan, C.; Brown, J.; Scorah, N. J Org Chem 2015, 80, 1564.
[12] Arzel, E.; Rocca, P.; Grellier, P.; Labaeıd, M.; Frappier, F.;
Gueritte, F.; Gaspard, C.; Marsais, F.; Godard, A.; Queguiner, G. J Med
Chem 2001, 44, 949.
[13] Tahri, A.; Buysens, K. J.; Van der Eycken, E. V.;
Vandenberghe, D. M.; Hoonaert, G. J Tetrahedron 1998, 54, 13211.
[14] Liger, F.; Popowycz, F.; Besson, T.; Picot, L.; Galmarini, C.
M.; Joseph, B. Bioorg Med Chem 2007, 15, 5615.
[15] Vera-Luque, P.; Alajarin, R.; Alvarez-Builla, J.; Vaquero, J.
J Org Lett 2006, 8, 415.
[16] Meyer, M.; Guyot, M. Tetrahedron Lett 1996, 37, 4931.
[17] Bonini, C.; Funicello, M.; Spagnolob, P. Synlett 2006 1574.
[18] Khoshneviszadeh, M.; Yahagh, A.; Soheilizad, M.; Mahdavi,
M. Heterocycl Commun 2017, 23, 293.
[19] Yang, T.-H.; Kuo, C.-W.; Kavala, V.; Konala, A.; Huang, C.-
Y.; Yao, C.-F. Chem Commun 2017, 53, 1676.
[20] Gupta, S.; Kumar, B.; Kundu, B. J Org Chem 2011, 76,
10154.
[21] Sheikhan-Shamsabadi, N.; Ghashang, M. Main Group Met
Chem 2017, 40, 19.
[22] Lou, Z.; Huang, B.; Wang, Z.; Ma, X.; Zhang, R.; Zhang, X.;
Qin, X.; Dai, Y.; Whangbo, M.-H. Chem Mater 2014, 26, 3873.
[23] Iler, R. K. The Chemistry of Silica, first ed.; Wiley: New York,
1979.
[24] Vail, J. G. Soluble Silicates, first ed.; Reinhold: New York,
1952.
290–292°C (mp 287–288°C19). 1H NMR spectrum, δ,
ppm (J, Hz): 7.03 (d, J = 7.6, 1H), 7.37–7.77 (m, 12H),
8.18 (d, J = 8.4, 1H), 12.11 (s, 1H, NH); 13C NMR
spectrum, δ, ppm: 111.4, 111.9, 112.9, 119.3, 120.2,
121.7, 122.3, 126.5, 127.8, 128.3, 128.6, 128.8, 129.2,
131.6, 138.6, 139.4, 145.7, 153.1, 153.9. Found: C,
69.08; H, 3.76; N, 6.93% C23H15BrN2. Calculated, %: C,
69.19; H, 3.79; N, 7.02% (Table 2).
2-(4-Nitrophenyl)-4-phenyl-9H-pyrido[2,3-b] indole (product
3o). Yield 0.332 g (91%), yellow solid, mp 294–296°C
1
(mp 296–297°C19). H NMR spectrum, δ, ppm (J, Hz):
7.04 (d, J = 7.6, 1H), 7.44 (t, J = 7.6, 1H), 7.52–7.77 (m,
7H), 8.19 (d, J = 8.2, 1H), 8.30 (d, J = 8.0, 2H), 8.48 (d,
J = 8.0, 2H), 12.23 (s, 1H, NH); 13C NMR spectrum, δ,
ppm: 111.7, 112.3, 113.1, 119.4, 120.2, 121.9, 122.3,
124.3, 127.6, 128.3, 129.0, 129.4, 129.9, 131.6, 138.7,
139.5, 146.7, 153.1, 154.1. Found: C, 75.56; H, 4.09; N,
11.42% C23H15N3O2. Calculated, %: C, 75.60; H, 4.14;
N, 11.50% (Table 2).
2-(4-Methoxyphenyl)-4-phenyl-9H-pyrido[2,3-b]
indole
(product 3p).
Yield 0.308 g (88%), white solid, mp
240–242°C (mp 236–237°C19). 1H NMR spectrum, δ,
ppm (J, Hz): 3.88 (s, 3H, OCH3), 6.74 (d, J = 7.8, 2H),
[25] Bahramian, F.; Fazlinia, A.; Mansoor, S. S.; Ghashang, M.;
Azimi, F.; Biregan, M. N. Res Chem Intermed 2016, 42, 6501.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Sheikh and A. Fazlinia
Vol 000
[26] Ghashang, M.; Kargar, M.; Shafiee, M. R. M.; Mansoor, S. S.;
Fazlinia, A.; Esfandiari, H. Recent Pat Nanotechnol 2015, 9, 204.
[27] Shafiee, M. M. R.; Ghashang, M.; Fazlinia, A. Curr Nanosci
2013, 9, 197.
[28] Shafiee, M. R. M.; Mansoor, S. S.; Ghashang, M.; Fazlinia,
A. C. R. Chimia 2014, 17, 131.
[29] Ghashang, M.; Mohammad Shafiee, M. R.; Delzendeh, S.;
Fazlinia, A.; Esfandiari, H.; Najafi Biregan, M.; Heydari, N. Bulg Chem
Commun 2016, 48, 694.
[30] Shafiee, M. R. M.; Fazlinia, A.; Yaghooti, N.; Ghashang, M.
Lett Org Chem 2012, 9, 351.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet