An efficient one-pot synthesis of a new heterocyclic system with high-fluorescent properties

Article abstract of DOI:10.1002/jhet.681

Nucleophilic substitution of hydrogen in nitro derivative of imidazo[1,2-a]pyridine has been used as a key step in the one-pot synthesis of a new highly fluorescent heterocyclic system pyrido [1″,2″:1′, 2′]imidazo[4′,5′:5,6]pyrido[2,3-b]indole..

Full text of DOI:10.1002/jhet.681

208
An Efficient One-Pot Synthesis of a New Heterocyclic System
with High-Fluorescent Properties
Vol 49
Mohammad Rahimizadeh,* Mehdi Pordel, Mahsa Ranaei, and Mehdi Bakavoli
Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad,
Mashhad 91775-1436, Iran
*E-mail: rahimizh@yahoo.com
Received March 13, 2010
DOI 10.1002/jhet.681
Published online 13 October 2011 in Wiley Online Library (wileyonlinelibrary.com).
Nucleophilic substitution of hydrogen in nitro derivative of imidazo[1,2-a]pyridine has been used as a key
step in the one-pot synthesis of
a
new highly fluorescent heterocyclic system pyrido
[100,200:10,20]imidazo[40,50:5,6]pyrido[2,3-b]indole.
J. Heterocyclic Chem., 49, 208 (2012).
INTRODUCTION
via the nucleophilic substitution of hydrogen of imia-
dazo[1,2-a]pyridine 1 with 2-(1-alkyl-1H-3-indolyl)aceto-
nitrile 2a–e in basic MeOH solution [4] in excellent yields
(Scheme 1). A tentative mechanism to explain the forma-
tion of compounds 3a–e is shown in Scheme 2.
It is well recognized and documented that addition of
nucleophilic agents to electrophilic arenes proceeds faster
in positions bearing hydrogen, resulting in the formation
of the dH-adducts, rather than their addition in positions
bearing leaving groups including halogens [1–3]. These
dH-adducts can be further transformed into products of
nucleophilic substitution of hydrogen via numerous mech-
anisms. One of the most general of these pathways is con-
version of dH-adducts into nitroso compounds under
proper conditions. This reaction can be considered as an
intramolecular redox process with release of hydroxide
ion. This conversion occurs usually in protic solvents
apparently via protonation of the negatively charged oxy-
gen of nitro group of the dH-adducts and elimination of
water [4–7]. These nitrosoarenes are mostly cyclized to
heterocyclic systems under the reaction conditions [8–12].
Continuing our study on the nucleophilic substitution
reactions of hydrogen in imidazo[1,2-a]pyridine [13,14]
and other heterocyclic systems [15–17], in this work, we
have introduced a useful one-pot method for the synthe-
sis of some fluorescent compounds through the conver-
sion of imidazo[1,2-a]pyridine dH-adducts into nitroso
compounds and transformation of them to a new hetero-
cyclic system such as pyrido[100,200:10,20]imidazo
[40,50:5,6]pyrido [2,3-b]indole-13-yl cyanides.
The structural assignments of compounds 3a–e were
based on the analytical and spectral data. For example,
1
in the H NMR spectrum of 3a, there are the signal at d
4.03 ppm assignable to protons of methyl group and the
doublet of doublet signal at d 6.96 ppm (J ¼ 7.9 Hz
and J0 ¼ 6.7 Hz), the multiplet signals at d 7.4–7.71
ppm, the doublet of signal at d 8.58 (d, J ¼ 6.9 Hz) and
the doublet signal at d 8.8 (d, J ¼ 8.4 Hz) attributed to
eight protons of aromatic rings. Moreover, the FTIR
spectrum of 3a in KBr showed the absorption band at
2240 cmꢀ1 corresponding to cyanide group. All these
evidences with the molecular ion peak at m/z 297 and
microanalytical data strongly support the pentacyclic
structure of compound 3a.
These compounds are highly fluorescent. When a het-
eronitrogen is singly bonded to carbon atoms in a het-
erocycle, as in pyrrole rings (e.g., indole, carbazole), the
transitions involving the nonbonding electrons have
properties similar to those of p–p* transitions. In fact,
the nonbonding orbital is perpendicular to the plane of
the ring, which allows it to overlap the p orbitals on the
adjacent carbon atoms.
The fluorescence absorption and emission spectra of
compounds 3a–e were recorded at the concentration of
10ꢀ5 and 10ꢀ6 M in chloroform as the solvent. Figures 1
and 2 show the visible absorption and emission spectra
of compounds 3a–e. Values of molar extinction
RESULTS AND DISCUSSION
The new 5-alkyl-5H-pyrido[100,200:10,20]imidazo[40,50:5,6]
pyrido [2,3-b]indole-13-yl cyanides 3a–e were synthesized
C
V
2011 HeteroCorporation

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One-Pot Synthesis of a New Heterocyclic System
209
Scheme 1
[19] and 2a–e [20,21] were obtained according to the pub-
lished methods. Other reagents were commercially available.
General procedure for the synthesis of 3a–e from 1 and
2a–e. Compounds 1 (1.63 g, 10 mmol) and 2a–e (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 2 h, and then poured into water, and then it was
neutralized with dilute HCl solution. The precipitate was col-
lected by filtration, washed with water, following with EtOH,
and then air dried to give 3a–e.
coefficient (e) were calculated as the slope of the plot of
absorbance versus concentration. The fluorescence quan-
tum yields (UF) of compounds 3a–e were determined
via comparison methods, using fluorescence as a stand-
ard sample in 0.1 M NaOH and MeOH solution [14,18].
The kmax, kex, kflu, and fluorescence quantum yields
(UF) data are presented in Table 1.
In conclusion, we have presented a facile, efficient, and
useful protocol for the synthesis of some fluorescent com-
pounds from nitro derivative of imidazo[1,2-a]pyridine.
5-Methyl-5H-pyrido[100,200:10,20]imidazo[40,50:5,6]pyrido[2,3-b]
indole-13-carbonitrile (3a). Compound 3a was obtained as shin-
ing yellow needles (EtOH), yield (91%), mp 325–327ꢁC; 1H
NMR (CDCl3, ppm): d 4.03 (s, 3H, CH3), 6.96 (dd, J ¼ 7.9 Hz,
J0 ¼ 6.7 Hz, 1H, pyridine), 7.4–7.71 (m, 5H, Phenyl and pyri-
dine protons), 8.58 (d, J ¼ 6.9 Hz, 1H, pyridine), 8.8 (d, J ¼ 8.4
Hz, 1H, pyridine) ppm; 13C NMR (CDCl3, ppm): d 34.33,
101.11, 109.37, 111.23, 115.19, 116.9, 118.33, 118.87, 120.31,
122.59, 124.63, 128.58, 130.97, 132.08, 139.59, 140.62, 146.11,
148.45 ppm; IR (KBr disk): m 2240 cmꢀ1 (CN). MS (m/z) 297
(Mþ). Anal. Calcd. for C15H8N4 (297.3): C, 72.72; H, 3.73; N,
23.56. Found: C, 73.15; H, 3.82; N, 23.29.
EXPERIMENTAL
5-Ethyl-5H-pyrido[100,200:10,20]imidazo[40,50:5,6]pyrido[2,3-b]
indole-13-carbonitrile (3b). Compound 3b was obtained as
Melting points were recorded on an Electrothermaltype-
9100 melting-point apparatus. The IR spectra were obtained on
a 4300 Shimadzu spectrometer, and only noteworthy absorp-
tions are listed. The 13C NMR (125 MHz) and the 1H NMR
(500 MHz) spectra were recorded on a Bruker Avance DRX-
500 Fourier transformer spectrometer. Chemical shifts are
reported in ppm downfield from TMS as internal standard;
coupling constant 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.
Absorption spectra were recorded on an Agilent 8453 spectro-
photometer. Fluorescence spectra were recorded using Shi-
madzu RF-1501 spectrofluorophotometer. UV–vis and fluores-
cence scans were recorded from 350 to 700 nm. All measure-
ments were carried out at room temperature. Compounds 1
1
shiny yellow needles (EtOH), yield (88%), mp 288–289ꢁC; H
NMR (CDCl3, ppm): d 1.51 (t, J ¼ 7.2 Hz, 3H, CH3), 4.63 (q, J
¼ 7.2 Hz, 2H, ACH2A), 7.01 (dd, J ¼ 7.9 Hz, J0¼ 6.7 Hz, 1H,
pyridine), 7.27–7.81 (m, 5H, phenyl and pyridine protons), 8.61
(d, J ¼ 6.9 Hz, 1H, pyridine), 8.83 (d, J ¼ 8.4 Hz, 1H, pyridine)
ppm; 13C NMR (CDCl3, ppm): d 13.93, 36.90, 100.22, 109.38,
111.27, 115.19, 116.94, 118.27, 118.74, 120.48, 122.61, 124.62,
128.58, 130.97, 132.07, 139.59, 140.62, 146.81, 148.43 ppm; IR
(KBr disk): m 2240 cmꢀ1 (CN). MS (m/z) 311 (Mþ). Anal.
Calcd. for C15H8N4 (311.3): C, 73.30; H, 4.21; N, 22.49. Found:
C, 73.41; H, 4.20; N, 22.71.
5-Propyl-5H-pyrido[100,200:10,20]imidazo[40,50:5,6]pyrido[2,3-
bindole-13-carbonitrile (3c). Compound 3c was obtained as
1
shiny yellow needles (EtOH), yield (71%), mp 268–270ꢁC; H
Scheme 2
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M. Rahimizadeh, M. Pordel, M. Ranaei, and M. Bakavoli
Vol 49
Figure 2. Emission spectrum of compounds 3a–e in dilute (1 ꢂ 10ꢀ6
M) chloroform solution. [Color figure can be viewed in the online
issue, which is available at wileyonlinelibrary.com.]
Figure 1. Visible absorption spectrum of compounds 3a–e in dilute (1
ꢂ 10ꢀ5 M) chloroform solution. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
Table 1
Photophysical data for absorption (abs) and fluorescence (flu) of 3a-e.
Dye
3a
3b
3c
3d
3e
kmax (nm)a
382, 446, 476
2.74, 1.48, 2.03
382, 446, 474
3.15, 1.68, 2.32
382, 446, 474
3.71, 1.91, 2.72
382, 446, 476
2.94, 1.48, 1.51
382, 444, 472
3.92, 2.07, 2.80
e ꢂ 10ꢀ4 (Mꢀ1 cmꢀ1 b
)
kex (nm)c
283
485
0.59
283
490
0.63
283
490
0.65
283
490
0.66
283
485
0.60
kflu (nm)d
e
UF
a Wavelengths of maximum absorbance (kmax).
b Molar extinction coefficient.
c Wavelengths of fluorescence excitation (kex).
d Wavelengths of fluorescence emission (kflu).
e Fluorescence quantum yield (UF).
NMR (CDCl3, ppm): d 1.02 (t, J ¼ 7.2 Hz, 3H, CH3), 1.81–
2.16 (m, 2H, ACH2A), 4.58 (t, J ¼ 7.2 Hz, 2H, ACH2A),
7.00 (dd, J ¼ 7.8 Hz, J0¼ 6.6 Hz, 1H, pyridine), 7.38–7.88
(m, 5H, phenyl and pyridine protons), 8.68 (d, J ¼ 7.0 Hz,
1H, pyridine), 8.9 (d, J ¼ 8.4 Hz, 1H, pyridine) ppm; 13C
NMR (CDCl3, ppm): d 10.55, 24.78, 39.38, 100.13, 109.38,
111.27, 115.19, 116.94, 118.27, 118.74, 120.48, 122.61,
124.62, 128.58, 130.97, 132.07, 139.59, 140.62, 146.95,
148.43 ppm; IR (KBr disk): m 2240 cmꢀ1 (CN). MS (m/z) 325
(Mþ). Anal. Calcd. for C15H8N4 (325.4): C, 73.83; H, 4.65; N,
21.52. Found: C, 73.41; H, 4.50; N, 21.71.
139.59, 140.62, 146.97, 148.43 ppm; IR (KBr disk): m 2240
cmꢀ1 (CN). MS (m/z) 339 (Mþ). Anal. Calcd. for C15H8N4
(339.4): C, 74.32; H, 5.05; N, 20.63. Found: C, 73.91; H,
5.15; N, 20.71.
5-Benzyl-5H-pyrido[100,200:10,20]imidazo[40,50:5,6]pyrido[2,3-b]
indole-13-carbonitrile (3e). Compound 3e was obtained as
1
shiny yellow needles (EtOH), yield (75%), mp 276–278ꢁC; H
NMR (CDCl3, ppm): d 5.80 (s, 2H, ACH2A), 7.05 (dd, J ¼
7.9 Hz, J0 ¼ 6.7 Hz, 1H, pyridine), 7.3–7.9 (m, 10H, phenyl
and pyridine protons), 8.65 (d, J ¼ 6.9 Hz, 1H, pyridine), 8.88
(d, J ¼ 8.4 Hz, 1H, pyridine) ppm; 13C NMR (CDCl3, ppm): d
49.35, 101.07, 109.31, 111.40, 115.18, 116.87, 118.23, 118.69,
120.53, 122.62, 123.76, 124.61, 124.78, 125.03, 125.81,
128.59, 130.99, 132.07, 139.58, 140.62, 146.53, 148.43 ppm;
IR (KBr disk): m 2240 cmꢀ1 (CN). Anal. Calcd. for C15H8N4
(373.4): C, 77.20; H, 4.05; N, 18.75. Found: C, 77.41; H,
4.20; N, 18.51.
5-Butyl-5H-pyrido[100,200:10,20]imidazo[40,50:5,6]pyrido[2,3-b]
indole-13-carbonitrile (3d). Compound 3d was obtained as
1
shiny yellow needles (EtOH), yield (67%), mp 232–235ꢁC; H
NMR (CDCl3, ppm): d 1.00 (t, J ¼ 6.7 Hz, 3H, CH3), 1.16–
1.51 (m, 2H, ACH2A), 1.75–2.01 (m, 2H, ACH2A), 4.59 (t, J
¼ 6.7 Hz, 2H, ACH2A), 6.96 (dd, J ¼ 7.8 Hz, J0¼ 6.6 Hz,
1H, pyridine), 7.26–7.90 (m, 5H, phenyl and pyridine protons),
8.58 (d, J ¼ 7.0 Hz, 1H, pyridine), 8.8 (d, J ¼ 8.4 Hz, 1H,
pyridine) ppm; 13C NMR (CDCl3, ppm): d 13.94, 18.65,
33.45, 38.48, 100.08, 109.38, 111.27, 115.19, 116.94, 118.27,
118.74, 120.48, 122.61, 124.62, 128.58, 130.97, 132.07,
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