Effect of specific solute-solvent interaction and electron donor-acceptor substituents of novel pyrazolo naphthyridines on fluorescence

Article abstract of DOI:10.1007/s10895-010-0707-0

Heterocyclic orthoaminoaldehyde such as 4-amino-3-(4-phenyl)-1-phenyl-1H- Pyrazolo[3,4-b]pyridine-5-carbaldehyde was synthesized by multistep reactions involving reduction of azido derivative 2 with LAH to yield aminoalcohol 3 and oxidation of it with MnO

Full text of DOI:10.1007/s10895-010-0707-0

J Fluoresc (2011) 21:461–471
DOI 10.1007/s10895-010-0707-0
RAPID COMMUNICATION
Effect of Specific Solute-Solvent Interaction and Electron
Donor-Acceptor Substituents of Novel Pyrazolo
Naphthyridines on Fluorescence
Sandeep R. Patil & Deepak P. Shelar & Ramhari V. Rote &
Raghunath B. Toche & Madhukar N. Jachak
Received: 3 February 2010 /Accepted: 9 August 2010 /Published online: 30 September 2010
#
Springer Science+Business Media, LLC 2010
Abstract Heterocyclic orthoaminoaldehyde such as 4-
amino-3-(4-phenyl)-1-phenyl-1H-Pyrazolo[3,4-b]pyridine-
5-carbaldehyde was synthesized by multistep reactions
involving reduction of azido derivative 2 with LAH to
yield aminoalcohol 3 and oxidation of it with MnO2 to
aminoaldehyde 4.The pyridine ring annulated on to 4 by
Friedländer condensation using acetophenones in presence
of base to obtained pyrazolo[3,4-h][1,6]naphthyridine 5 in
excellent yield. Study of photophysical properties of 5
revealed that the absorption and emission of them depends
up on the substituents present on benzene ring in newly
annulated pyridine ring.
by a number of different reductive methods. The aldehyde
function is thus elaborated in the presence of the amino
group, in contrast with the standard method employed in
the carbocyclic series wherein the reverse order of
introduction is followed. Catalytic reduction of amino-
nitriles, conducted in acid medium to hydrolyze the
intermediate amino imines, is a valuable synthetic method
for heterocyclic aminoaldehyde, since the starting amino-
nitriles are readily accessible [3].
In our earlier communication we have introduce the
aldehyde functionality by Vilsmeier-Haack formylation of 5-
aminopyrazole [4] and resulted orthoaminoaldehyde after
hydrolysis was utilized for annulation of various hetrocyclic
ring on to 5-aminopyrazole-4-carbaldehydes by Friedländer
condensation with reactive methylenes. Recently we have
reported the synthesis of orthoaminoaldehyde on to quinoline
nucleus introduced by azidation of orthochloroquinoline-3-
carbaldehyde and subsequent reduction of azido functionality
using triphenylphosphine to yield 2-aminoquinoline-3-carbal-
dehyde, in our laboratry. The Friedländer condensation of it
with reactive methylenes were performed [5] and resulted
naphthyridines were studied for their photophysical analysis.
From literature it was also noted that naphthyridine
derivatives were not only use as luminescence materials in
molecular recognition because of their rigid planer structure
[6–8], but also as new drug leaders [9, 10] and anticancer
active screening agents in new drug discovery [11, 12].
These literature reports and our ongoing interest in this area
prompted us for the synthesis of new heterocyclic orthoami-
noaldehyde. In this communication we are reporting the
synthesis of novel orthoaminoaldehyde on pyrazolo [3, 4-b]
pyridine nucleus. Then the pyridine nucleus annulated on it by
Friedländer condensation with acetophenone to obtained
naphthyridine derivatives and studied their photophysical
properties.
.
Keywords Chloroester Pyrazolo[3,4-b]pyridine-5-
.
.
carbaldehyde Pyrazolo[3,4-h] [1,6]naphthyridine
.
.
HOMO-LUMO Quantum yields Absorption
and emission
Introduction
Annulation reactions with hetrocyclic aminoaldehydes
provides synthectic entry in to hetrocyclic systems fused
to a pyridine or pyrimidine nucleus by condensation
reactions with reactive methylenes. It was noted from
literature [1, 2], that heterocyclic orthoaminoaldehydes are
generally accessible from aminocarboxylic acid precursors
:
:
:
:
S. R. Patil D. P. Shelar R. V. Rote R. B. Toche
M. N. Jachak (*)
Organic Chemistry Research Centre, Department of Chemistry,
KTHM College,
Gangapur Road,
Nashik, MS, India
e-mail: mnjachak@hotmail.com

462
J Fluoresc (2011) 21:461–471
Result and Discussion
these molecules. In this compound the practical results
obtained are in agreement with the HOMO-LUMO, Heat
of formation obtained by semi-empirical PM3/PM6
methods.
The orthoaminoaldehyde 4 required for this work was
synthesized by multistep reactions. Thus, the chloroester 1
synthesized by lit. Method [13], then introduction of
aminoaldehyde functionality on 1 was accomplished via
the azidation of 1 with sodium azide in DMF to obtain the
azido ester 2 [14]. Then, the formyl group was incorporated
by oxidation of alcohol 3 with MnO2 (without protecting
amino group), obtained by reduction of 2 with LAH. In this
step, expected N-oxide was not formed as revealed by
spectral and analytical data. The orthoaminoaldehyde 4
Spectral Properties
Absorption Spectra
The absorption spectra (UV model- Shimadzu UV-1601
UV-VIS spectrophotometer) of the synthesized pyrazolo
[3,4-h][1,6]naphthyridine 5a–x (Table 2) were taken in non-
polar dichloromethane, polar aprotic acetonitrile and polar
protic methanol solvents at room temperature. All absorp-
tion band maxima are given in Table 2 and spectra for 5x
are shown in all three solvents in Fig. 2. In all pyrazolo
[3,4-h][1,6]naphthyridines have chromophore present on
the substituted benzene ring i.e. on D ring (Fig 1). The
spectral pattern and band maxima clearly indicate that the
observed absorption band corresponds to substituents
present on D ring. High absorbance values indicate that
these transitions are from π→ π* transition of the
substituted benzene ring. It was also observed that the
absorption band maxima are slightly solvent dependent
indicating less polar character of these molecules in the
ground state. In protic solvent the band shows a blue shift
due to intermolecular hydrogen bond between solvent
methanol and the solute with several possible hydrogen
bond making centers.
obtained was characterized by IR, H NMR, 13C NMR,
1
mass and elemental analysis. For instance, Compound 4a
shows broad singlet at 6.65δ in its 1H NMR, corresponds to
two protons of -NH2 and singlet at 9.75δ corresponds to
aldehydic proton. All aromatic protons showed expected
chemical shifts and splitting patterns which resembles with
the structure of 4a. The mass spectrum of 4a revealed a
molecular ion peak m/z at 348. The 13C NMR spectrum of
this compound is agreement with the structure proposed. In
our approach, the yields of intermediates 2, 3 and 4 are
excellent. This method is versatile and scalable.
The base catalyzed Friedländer condensation with
acetophenone can be studied with compound orthoaminoal-
dehyde 4. Thus compound 4 and acetophenone/substituted
acetophenone on condensation in refluxing ethanol using
KOH as a base yielded a naphthyridine derivative 5 in 80–
90% yields and were characterized by IR, H NMR, 13C
NMR, mass and elemental analysis. These compounds
are further studied for their photophysical properties
(Scheme 1).
1
Emission Spectra
Usually naphthyridine compounds are highly fluorescent
after excitation to the locally exited state and some of the
naphthyridine derivatives show interesting photo-induced
properties. Therefore, we have tried to measure emission
and excitation spectra of these molecules in all the three
solvents after excitation of the emission band maxima as
shown in Fig. 3 (for 5x), the excitation of each molecule at
their corresponding absorption band of each substituted
naphthyridine shows single emission band (RF-5301 PC
Spectrofluorophotometer) in the wavelength range ~370 nm
to ~495 nm which was due to emission from their locally
excited state. The emission band maxima and the
corresponding fluorescence quantum yields are shown in
Table 2. In general, in the emission bands are found to be
similar in aprotic solvents (dichloromethane and acetoni-
trile). This indicates that stabilization of the ground and
excited state is not modified with polarity of the solvents.
On the other hand, in protic solvent (methanol) the
emission band shifts to the blue due to intermolecular
hydrogen bond interaction between solvent and solute. As
Semi-Empirical Study
From literature it was noted that pyrazolonaphthyridine
derivatives are not explored for their photophysical prop-
erties. Hence, we had undertaken semi-empirical calcula-
tions such as HOMO-LUMO energy, Heat of formation,
Ionization potential, and Electron hole gap (gap value)
before determination of their UV and Emission spectra.
We analyzed the three dimensional coefficient contribu-
tion by the MOPAC 2009 (Version 8.331) [15, 16] and are
given in Table 1. From these we observed that there is more
overlapping between the HOMO-LUMO energy for 5h, 5i,
5j, 5k, 5l, 5t, 5u, 5v, 5w and 5x which shows low gap value
and high heat of formation hence more stability. (Table 1).
The 3D picture of pyrazolnaphthyridine 5 is depicted in
Fig. 1. The charge is more concentrated on ring D as
compared to ring A, B and C. The donor chromophore
on ring D is playing important role in increasing electron
density hence increased the stability and reactivity of

J Fluoresc (2011) 21:461–471
463
R
R
R
Cl
N
O
N3
N
O
NH2
N
O
O
OH
N
NaN3,DMF
RT 3H
LiAlH4, THF
RT
N
N
N
N
N
1
3
2
R3
CH2Cl2,DMF
RT, 24h
MnO2
R4
R5
R2
R1
R
O
R
R1
R2
R3
NH2
N
O
N
CH3
R5
H
R4
N
N
N
N
N
KOH/ EtOH
25-30 min reflux
5
4
Scheme 1 Synthetic route of Pyrazolo [3, 4-h] [1, 6] naphthyridines
5 (a-x)
R
R1
H
H
H
H
Br
H
H
H
H
R2
H
H
H
Cl
H
H
H
CF3
H
OCH3
H
H
H
H
H
Cl
H
H
H
CF3
H
R3
H
Cl
Br
Cl
Cl
CH3
NO2
H
OCH3
OCH3
H
OCH3
H
Cl
Br
Cl
Cl
CH3
NO2
H
OCH3
OCH3
H
R4
H
H
H
H
H
H
H
CF3
H
H
OCH3
H
H
H
H
H
H
H
R5
H
H
H
H
H
H
H
H
H
H
H
OCH3
H
H
H
H
H
H
H
H
H
H
H
OCH3
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
s
t
u
v
w
x
H
OCH3
OCH3
H
H
H
H
Br
H
H
H
H
CF3
H
H
OCH3
H
H
H
OCH3
OCH3
OCH3
H
H
OCH3

464
J Fluoresc (2011) 21:461–471
Table 1 The molecular electronic properties (HOMO-LUMO energy, GAP) of the Pyrazolo [3,4-h][1,6]naphthyridine 5 (a–x)
Comp.
R
R1
R2
R3
R4
R5
Heat of Formation Ionization Potential (eV) HOMO (eV) LUMO (eV) GAP (eV)
(K Cal.)
5a
5b
5c
5d
5e
5f
Cl
Cl
Cl
Cl
H
H
H
H
H
H
H
H
165.11
155.03
167.08
149.56
158.91
154.46
160.96
−159.11
123.25
88.90
8.718
8.819
8.829
8.846
8.803
8.699
8.965
8.978
8.656
8.500
8.507
8.485
8.771
8.858
8.837
8.920
8.844
8.735
9.00
−8.719
−8.820
−8.829
−8.846
−8.804
−8.700
−8.965
−8.978
−8.657
−8.501
−8.507
−8.486
−8.772
−8.859
−8.838
−8.921
−8.845
−8.736
−9.007
−8.992
−8.685
−8.502
−8.510
−8.512
−1.373
−1.480
−1.499
−1.607
−1.463
−1.295
−1.885
−1.805
−1.273
−1.311
−1.230
−0.968
−1.369
−1.490
−1.528
−1.597
−1.473
−1.306
−1.893
−1.786
−1.283
−1.323
−1.243
−0.977
7.346
7.340
7.330
7.230
7.341
7.405
7.080
7.173
7.384
7.170
7.277
7.518
7.403
7.369
7.310
7.324
7.372
7.430
7.114
7.206
7.400
7.179
7.267
7.535
H
Cl
H
H
H
Br
H
H
Cl
H
Cl
H
H
Cl Br
Cl
H
H
Cl
Cl
Cl
Cl
Cl
H
H
H
H
H
H
CH3
NO2
H
H
H
5g
5h
5i
H
H
H
CF3
H
CF3
H
H
OCH3
H
5j
OCH3 OCH3
H
H
5k
5l
Cl OCH3
Cl OCH3
H
H
OCH3
H
H
87.62
H
OCH3
H
OCH3
H
40.59
5m
5n
5o
5p
5q
5r
Br
Br
Br
Br
H
H
H
H
H
H
177.05
167.00
179.23
161.35
170.90
166.49
172.94
−145.82
135.22
100.89
99.59
H
Cl
H
H
H
Br
H
H
Cl
H
Cl
H
H
Br Br
Cl
H
H
Br
Br
Br
Br
Br
H
H
H
H
H
H
CH3
NO2
H
H
H
5s
5t
H
H
H
CF3
H
CF3
H
H
8.992
8.685
8.501
8.510
8.512
5u
5v
5w
5x
OCH3
H
OCH3 OCH3
H
H
Br OCH3
Br OCH3
H
H
H
OCH3
H
H
OCH3
OCH3
52.36
GAP = ELUMO-EHOMO
the absorption band shifts to the blue, the emission band
also shifts to the blue and this blue shifted emission is
nothing but the local emission from the hydrogen bonded
clusters. We have measured fluorescence quantum yield of
these compounds by using quinine sulphate as reference
standard (ϕref=0.54 in 0.1 M H2SO4) [17]. The fluores-
cence quantum yield of these studied systems is very high
in polar aprotic solvent and very poor in hydrogen bonding
solvent methanol. Weak intermolecular hydrogen bonding
interaction usually triggered non-radiative channels and
hence fluorescence quantum yield is very low in methanol
solvent [18].
Further it was noted that halo-substituted molecules have
less fluorescence quantum yield as compared to methoxy
substituted compounds. This may be due to quenching of
fluorescence with halogen atoms as the substituent. Pyr-
azolonaphthyridine 5u, 5v, 5w and 5x having donor
chromophores e.g. C4-OCH3, C3 & C4-di-OCH3, C2
&
C5-di-OCH3, C2, C4 & C6-tri-OCH3 on phenyl ring sowed
absorption and emission maxima at 477 nm, 484 nm,
479 nm and 495 nm and quantum yields (ϕF) 0.248, 0.309,
0.292 and 0.345 respectively. Compound 5s having
acceptor chromophore e.g. C4-NO2 on phenyl ring showed
large decrease in emission maxima at 441 nm and quantum
yield (ϕF) 0.185 (Table 2). High quantum yield of these
molecules and sensitivity of the emission band on polarity
and hydrogen bonding ability of solvent could be useful to
be a good fluorescence sensor.
Fig. 1 3D picture of Pyrazolo [3, 4-h] [1, 6] naphthyridines

J Fluoresc (2011) 21:461–471
465
Table 2 (continued)
Comp. Solvents λAbs. (nm) λEm. (nm) Quantum Yield (ff)
Table 2 The photophysical data for electronic absorption (UV λMax.),
fluorescence (Em λMax.) and quantum yield (fF) of Pyrazolo[3,4-h]
[1,6]naphthyridine 5 (a-x) for 0.1 M Conc. at room temp
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
373
377
375
375
368
365
367
371
368
369
374
370
369
376
371
371
372
368
369
375
371
369
376
371
373
469
474
471
469
479
476
471
441
437
433
491
489
485
477
475
470
484
481
472
479
477
466
495
487
458
0.277
0.286
0.281
0.279
0.289
0.285
0.284
0.185
0.181
0.179
0.326
0.325
0.322
0.284
0.283
0.280
0.309
0.307
0.298
0.292
0.289
0.277
0.345
0.338
0.284
Comp. Solvents λAbs. (nm) λEm. (nm) Quantum Yield (ff)
5q
5r
5a
5b
5c
5d
5e
5f
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
CH3OH
CH2Cl2
CH3CN
370
364
368
371
369
366
373
368
364
375
371
372
379
375
369
370
367
366
385
377
379
377
371
372
373
370
370
379
374
374
378
370
373
379
377
377
368
363
365
369
367
365
371
365
363
374
370
457
456
452
466
464
459
472
470
467
470
468
465
471
469
465
474
471
464
438
435
429
488
484
481
467
466
463
477
473
461
473
469
460
490
487
455
460
459
455
469
467
461
475
472
466
475
471
0.264
0.259
0.258
0.278
0.272
0.270
0.281
0.277
0.278
0.280
0.279
0.278
0.271
0.268
0.269
0.273
0.271
0.266
0.179
0.176
0.174
0.330
0.327
0.328
0.277
0.275
0.273
0.295
0.288
0.281
0.281
0.279
0.271
0.339
0.324
0.298
0.272
0.270
0.271
0.281
0.278
0.274
0.281
0.277
0.275
0.282
0.279
5s
5t
5u
5v
5w
5x
5g
5h
5i
Conclusion
In this communication novel Pyrazolo[3,4-h][1,6]naphthyr-
idine derivatives has been synthesized by Friedländer
condensation using hitherto not described hetrocyclic orthoa-
minoaldehyde 4 and acetophenones. These intresting Pyr-
azolo[3,4-h][1,6]naphthyridine 5 are studied for their
photophysical properties in protic and aprotic solvents. It
was observed that quantum yield of compounds is solvent
dependent and greatly influenced by the nature of substituent
present in the benzene ring on newly annulated pyridine ring.
The donor substituent (OCH3) increases the fluorescence and
acceptor substituent (NO2) decreases fluorescence as well as
quantum yields. The empirical calculations of compounds 5
are in agreement with the observed values of emissions. For
instance naphthyridine derivatives 5l and 5x having low
LUMO energy values showed red shift and high quantum
yields (ϕF =0.339 and 0.345) as compared to other
derivatives of 5. Thermal analysis of compounds 5a–x by
differential scanning calorimetry (DSC) shows that they are
thermally stable up to 350°C. The efficient blue light
emission and physical and chemical stability makes Pyrazo-
lonaphthyridine a promising family of materials which may
5j
5k
5l
5m
5n
5o
5p

466
J Fluoresc (2011) 21:461–471
(20 mL) at 0°C and extracted in ethyl acetate (2×20 mL).
The combined organic layer was washed with water (2×
15 mL), then dried over anhydrous sodium sulfate, filtered
and the solvent was evaporated under reduced pressure, the
crude solid was taken in ethanol, filtered and dried under
high vacuum to provide 3 as a colorless solid,
4-Amino-3-(4-Cl-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]
pyridine-5-yl)-methanol (3a)
Yield: 3.22 g (77%); mp 188–189°C; IR (KBr): 3479 (s), 3369
1
(m), 3302 (m), 2964 (m), 1611 (s), 1505 (s) cm−1; H NMR
(DMSO-d6): 4.53 (d, 2H, J=5.7 Hz, CH2), 5.04 (t, 1H, J =
5.7 Hz, OH, D2O exchangeable), 6.29 (bs, 2H, NH2, D2O
exchangeable), 7.19 (t, 1H, J=7.4 Hz, Ar-H), 7.45 (t, 2H, J =
7.4 Hz, Ar-H), 7.61(d, 2H, J = 7.5 Hz Ar-H), 8.01 (s, 1H,
Ar-H), 8.26 (d, 2H, J = 7.4 Hz, Ar-H), 8.30 (d, 2H, J =
7.5 Hz Ar-H); 13C NMR (DMSO-d6): δ 59.9, 107.6, 115.3,
119.6 (2 C’s), 126.6, 127.7 (2 C’s), 128.6 (2 C’s), 129.4 (2
C’s), 130.8, 132.1, 134.2, 144.3, 148.4, 152.7, 152.4; MS
(70 eV) m/z (%) : 350 [M+] (100), 352 [M+2] (28); Anal.
Calcd. for C19H14N4OCl (349.75): C, 65.14; H, 4.00; N,
16.00. Found: C, 65.12; H, 4.02; N, 15.98.
Fig. 2 Absorption Spectra of compound 5x
be useful in opto-electronic applications and are addition in
the library of new heterocyclic compounds.
Experimental
General
4-Amino-3-(4-Br-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]
pyridine-5-yl)-methanol (3b)
Melting points were determined on a Gallenkamp melting
point apparatus, Mod. MFB595 in open capillary tubes and
Yield: 3.22 g (77%); mp 185–186°C; IR (KBr): 3479 (s), 3369
1
1
are uncorrected. H (300 MHz) and 13C (75 MHz) NMR
(m), 3302 (m), 2964 (m), 1611 (s), 1505 (s) cm−1; H NMR
spectra were measured on a Varian XL-300 spectrometer
using tetramethylsilane as the internal standard. IR spectra
were recorded using a Shimadzu IR-408, a Shimadzu FTIR
instrument with potassium bromide discs. Mass spectrum
was recorded on Shimadzu GC-MS QP mass spectrometer
with an ionization potential of 70 eV. Elemental analysis
were obtained on a Hosli CH-Analyzer and are within 0.3
of the theoretical percentage.
(DMSO-d6): 4.53 (d, 2H, J=5.7 Hz, CH2), 5.04 (t, 1H, J =
5.7 Hz, OH, D2O exchangeable), 6.29 (bs, 2H, NH2, D2O
exchangeable), 7.19 (t, 1H, J=7.4 Hz, Ar-H), 7.45 (t, 2H, J =
7.4 Hz, Ar-H), 8.01 (s, 1H, Ar-H), 7.61 (d, 2H, J = 7.4 Hz
Ar-H), 8.26 (d, 2H, J = 7.4 Hz, Ar-H) 8.30 (d, 2H, J =
7.4 Hz Ar-H); 13C NMR (DMSO-d6): δ 59.9, 107.6, 115.3,
119.6 (2 C’s), 126.6, 127.7 (2 C’s), 128.6 (2 C’s), 129.4 (2
C’s), 130.8, 132.1, 134.2, 144.3, 148.4, 152.7, 152.4; MS
All reactions were monitored by thin layer chromatog-
raphy on 0.2 mm silica gel F-254 (Merck) plates using UV
light (254 and 366 nm) for detection. Common reagents-
grade chemicals were either commercially available and
were used without further purification or prepared by
standard literature procedures.
4-Amino-3-(4-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]
pyridine-5-yl)-methanol(3a–b)
A solution of 1 (4.18 g, 0.01 mol) in tetrahydrofuran
(15 mL) was added slowly into the dispersed lithium-
aluminium hydride (2.17gm, 4 mol) in tetrahydrofuran
(20 mL) at 0°C, after addition the reaction mass was
allowed to come at 25°C and stirred it for 4 h. The reaction
mass was quenched with saturated sodium sulfate solution
Fig. 3 Emission Spectra of compound 5x

J Fluoresc (2011) 21:461–471
467
(70 eV) m/z (%) : 393 [M+] (89), 395 [M+2] (95). Anal.
Calcd. for C19H14N4OBr (394.20) : C, 58.01; H, 3.56; N,
14.24. Found: C, 58.05; H, 3.59; N, 14.27.
mixture was cooled to room temperature and the obtained
solid was collected by suction filtration and washed with
ethanol to furnish compound 5 in 80–90% yield and
recrystallized from ethanol.
4-Amino-3-(4-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]
pyridine-5-carbaldehyde(4a–b)
9-(4-Chloro-phenyl)-2,7-diphenly-7H-pyrazolo[3,4-h][1,6]
naphthyridine (5a)
Manganese(IV)dioxide (2.58 g, 3 mol) was added into the
solution of 3 (3.50 g, 0.01 mol) in dichloromethane
(20 mL) at 25°C for 24 h. After completion of reaction
(TLC check). The reaction mass was filtered through celite
and evaporated dichloromethane under reduced pressure,
the crude solid was washed with methanol,filtered, dried
under high vacuum and recrystallized from Ethanol: DMF
(8:2) to gives 4 as a pale yellow solid.
This compound was obtained as a pale brown solid, 0.388 g
(89%); mp 212–213°C; IR (KBr): 2925 m, 1610 s, 1510 s
1
cm−1; H NMR (CDCl3): 7.35 (t, 1H, J=7.8 Hz, Ar-H),
7.51–7.62 (m, 5H, Ar-H), 8.01 (d, 1H, J=8.4 Hz, Ar-H),
8.25 (d, 2H, J=7.8 Hz, Ar-H), 8.35 (d, 2H, J=8.2 Hz, Ar-
H), 8.42 (d, 1H, J = 8.4 Hz, Ar-H), 8.45(d, 2H, J = 8.6 Hz,
Ar-H),8.64(d, 2H, J = 8.6 Hz, Ar-H), 9.08 (s, 1H, Ar-H);
MS (70 eV) m/z (%): 432 [M+] (100), 433 [M+1] (28);
Anal. calcd. for C27H17N4Cl (432.87): C, 75.00; H, 3.93; N,
12.96. Found: C, 75.02; H, 3.91; N, 12.95.
4-Amino-3-(4-Cl-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]
pyridine-5-carbaldehyde (4a)
Yield: 3.28 g (93%); recrystalized from Ethanol:DMF (8:2) (v:
v) to afford yellow solid mp 181–182°C; IR (KBr): 3487 (m),
3335 (m), 2922 (s), 2775 (s), 1658 (s), 1618 (s), 1502 (s) cm−1;
1H NMR (DMSO-d6) δ: 6.65 (bs, 2H, NH2), 7.29 (t, 1H, J=
7.6 Hz, Ar-H), 7.49 (t, 2H, J = 7.6 Hz, Ar-H), 7.78 (d, 2H,
J=8.4 Hz, Ar-H), 8.08 (d, 2H, J=7.6 Hz, Ar-H) 8.20 (d, 2H,
J = 7.4 Hz Ar-H), 8.43 (s, 1H, Ar-H), 9.75 (s, 1H, -CHO).
13C NMR (DMSO-d6): δ 17.64, 106.26, 112.67, 123.73 (2
C’s), 128.68 (2 C’s), 131.71, 141.48, 146.83, 153.98, 155.24,
161.26, 195.56; MS (70 eV) m/z (%) : 348 [M+] (100), 350
[M+2] (33); Anal. Calcd. for C19H12N4OCl (347.74): C,
65.51; H, 3.44; N, 16.09. Found: C, 65.52; H, 3.46; N, 16.11.
2,9-Bis(4-chloro-phenyl)-7-diphenyl-7H-pyrazolo[3,4-h]
[1,6]naphthyridine(5b)
This compound was obtained as a yellow solid, 0.404 g
(86%); mp 235–236°C; IR (KBr): 2924 m, 1610 s, 1500 s
cm−1; 1H NMR (DMSO-d6): 7.29–7.37 (m, 5H, Ar-H), 7.56
(d, 2H, J=8.4 Hz, Ar-H), 7.98 (d, 2H, J = 8.4 Hz, Ar-H),
8.03 (d, 1H, J = 8.7 Hz, Ar-H), 8.28 (d, 2H, J = 8.6 Hz, Ar-
H) 8.49 (d, 2H, J = 8.6 Hz, Ar-H), 8.72 (d, 1H, J = 8.7 Hz,
Ar-H), 9.14 (s,1H, Ar-H); MS (70 eV) m/z (%): 467 [M+]
(100), 469 [M+2] (62), 471 [M+4] (14); Anal. Calcd. for
C27H16N4Cl2 (467.45): C, 69.37; H, 3.42; N, 11.99. Found:
C, 69.39; H, 3.46; N, 11.98.
4-Amino-3-(4-Br-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]
pyridine-5-carbaldehyde (4b)
2-(4-Bromophenyl)-9-(4-chloro-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6] naphthyridine(5c)
Yield: 3.28 g (93%); recrystalized from Ethanol:DMF (8:2)
(v:v) to afford yellow solid mp 184–185°C; IR (KBr): 3487
(m), 3335 (m), 2922 (s), 2775 (s), 1658 (s), 1618 (s), 1502 (s)
This compound was obtained as a yellow solid, 0.440 g
(86%); mp 247–248°C; IR (KBr): 2923 m, 1608 s, 1501 s
1
1
cm−1; H NMR (DMSO-d6) δ: 6.65 (bs, 2H, NH2), 7.29 (t,
cm−1; H NMR (DMSO-d6): δ 7.25–7.32 (m, 3H, Ar-H),
1H, J=7.6 Hz, Ar-H), 7.49 (t, 2H, J = 7.6 Hz, Ar-H), 7.78 (d,
2H, J=8.4 Hz, Ar-H), 8.08 (d, 2H, J=7.6 Hz, Ar-H), 8.20 (d,
2H, J =7.4 Hz Ar-H), 8.43 (s, 1H, Ar-H), 9.75 (s, 1H, CHO).
13C NMR (DMSO-d6): δ 17.64, 106.26, 112.67, 123.73 (2
C’s), 128.68 (2 C’s), 131.71, 141.48, 146.83, 153.98, 155.24,
161.26, 195.56; MS (70 eV) m/z (%): 391 [M+] (86), 393 [M+
2] (96); Anal. Calcd. for C19H12N4OBr (392.19): C, 58.31; H,
3.06; N, 14.32. Found: C, 58.33; H, 3.05; N, 14.30.
7.46 (t, 4H, J=8.4 Hz, Ar-H), 7.74 (d, 2H, J = 8.7 Hz, Ar-H),
8.02 (d, 1H, J = 8.7 Hz, Ar-H), 8.28 (d, 2H, J = 8.6 Hz,
Ar-H) 8.49 (d, 2H, J = 8.6 Hz, Ar-H), 8.82 (d, 1H, J =
8.7 Hz, Ar-H), 9.16 (s, 1H, Ar-H); MS (70 eV) m/z (%): 510
[M+] (72), 512 [M+2] (88), 514 [M+4] (34); Anal. Calcd.
For C27H16N4ClBr (511.90): C, 63.52; H, 3.13; N, 10.98.
Found: C, 63.55; H, 3.12; N, 10.97.
9-(4-Chloro-phenyl)-2-(3,4-dichloro-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6] naphthyridne (5d)
General Procedure for the synthesis of compounds (5a–x)
A mixture of 4 (0.001 mol), substituted acetophenones
(0.001 mol) and ethanolic potassium hydroxide solution
(5 mL, 2%) was heated under reflux for 25–30 min. The
This compound was obtained as a colorless solid, 0.435 g
(87%); mp 252–253°C; IR (KBr): 2930 m, 1614 s, 1508 s
1
cm−1; H NMR (DMSO-d6): δ 7.28 (d, 1H, J=8.4 Hz,

468
J Fluoresc (2011) 21:461–471
Ar-H), 7.47 (t, 1H, J=7.5 Hz, Ar-H), 7.59 (d, 2H, J = 7.5 Hz,
Ar-H), 7.63 (t, 2H, J = 7.5 Hz, Ar-H), 7.99 (dd, 1H, J=
8.4 Hz & J=2.3 Hz Ar-H), 8.21 (d, 1H, J=8.6 Hz, Ar-H),),
8.52 (d, 1H, J=2.3 Hz, Ar-H), 8.64 (d, 2H, J=8.7 Hz, Ar-H),
8.71 (d, 1H, J = 8.6 Hz, Ar-H), 8.80 (d, 2H, J = 8.7 Hz, Ar-
H), 9.03 (s, 1H, Ar-H); MS (70 eV) m/z (%): 500 [M+] (96),
502 [M+2] (97), 504 [M+4] (31), 506 [M+6] (7); Anal.
Calcd. for C27H15N4Cl3 (501.90): C, 64.67; H, 2.99; N,
11.17. Found: C, 64.69; H, 2.96; N, 11.18
C27H16ClN5O2 (477.99): C, 67.92; H, 3.35; N, 14.67.
Found: C, 67.89; H, 3.37; N, 14.69.
9-(4-Chloro-phenyl)-2-(3,4-diCF3-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6] naphthyridne (5h)
This compound was obtained as a yellow needle, 0.495 g
(87%); mp 236–237°C; IR (KBr): 2930 m, 1604 s, 1505 s
cm−1; 1H NMR (CDCl3): δ7.43(t, 1H, J=8.5 Hz, Ar-
H),7.54(t, 2H, J = 8.5 Hz, Ar-H), 7.61(d, 2H, J = 8.5 HZ,
Ar-H), 8.08(s, 1H, Ar-H), 8.11(d, 1H, J = 8.7 Hz, Ar-H),
8.37(d, 2H, J = 8.4 Hz, Ar-H), 8.41(d, 2H, J = 8.4 Hz, Ar-
H), 8.56(d, 1H, J = 8.7 Hz, Ar-H), 8.62(s, 2H, Ar-H), 9.11
(s, 1H, Ar-H) MS (70 eV) m/z (%): 568 [M+] (100), 570
[M+2] (27) Anal. Calcd. For C29H15N4F6Cl (568.83): C,
61.26; H, 2.64; N, 9.85. Found: C, 61.28; H, 2.63; N, 9.86.
2-(2-Bromo-4-chloro-phenyl)-9-(4-chloro-phenyl)-7-
phenyl-7H-pyrazolo[3,4-h][1,6] naphthyridine (5e)
This compound was obtained as a brown solid, 0.455 g
(83%); mp 249–250°C; IR (KBr): 2930 m, 1605 s, 1507 s
cm−1; 1H NMR (DMSO-d6): δ 7.25(dd, 1H, J=8.4 &
2.6 Hz, Ar-H), 7.44 (t, 1H, J=7.5 Hz, Ar-H), 7.52 (d, 2H,
J = 7.5 Hz, Ar-H), 7.58 (t, 2H, J = 7.5 Hz, Ar-H), 7.78 (d,
1H, J=2.6 Hz Ar-H), 8.20(d, 1H, J=8.4 Hr, Ar-H), 8.26 (d,
1H, J = 8.6 Hz, Ar-H), 8.67 (d, 2H, J = 8.7 Hz, Ar-H), 8.73
(d, 1H, J = 8.6 Hz, Ar-H), 8.82 (d, 2H, J = 8.7 Hz, Ar-H),
9.04 (s, 1H, Ar-H); MS (70 eV) m/z (%): 545 [M+] (96),
502 [M+2] (97), 504 [M+4] (31), 506 [M+6] (7); Anal.
Calcd. for C27H15N4Cl2Br (546.35): C, 59.49; H, 2.75; N,
10.27. Found: C, 59.54; H, 2.71; N, 10.29.
9-(4-Chloro-phenyl)-2-(4-methoxy-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6] naphthyridine(5i)
This compound was obtained as a silver needle, 0.410 g
(88%); mp 239–240°C; IR (KBr): 3022 m, 2919 s, 1596 s,
1
1501 s, 1070 mcm−1; H NMR (CDCl3): δ 3.93(s, 3H,
OCH3), 7.19(d, 2H, J=8.7 Hz,Ar-H), 7.42(t, 1H, J=7.6 Hz,
Ar-H), 7.56(t, 2H, J = 7.6, Ar-H), 7.61(d, 2H, J = 7.6 Hz,
Ar-H), 7.99(d, 1H, J=8.4 Hz, Ar-H), 8.28(d, 2H, J =
8.7 Hz, Ar-H), 8.38(d, 2H, J = 8.6 Hz, Ar-H), 8.40(d, 1H,
J = 8.4 Hz, Ar-H), 8.63(d, 2H, J = 8.6 Hz, Ar-H), 9.07
(s,1H, Ar-H), 13C NMR (CDCl3): δ 58.45, 115.24, 116.78,
120.17 (2 C’s), 124.38, 125.85, 126.17 (2 C’s), 127.27 (2
C’s), 128.90 (2 C’s), 129.14 (2 C’s), 132.23 (2 C’s), 133.99,
134.26, 135.20, 137.57, 138.96, 142.95, 145.64, 146.23,
148.52, 150.66, 158.97 MS (70 eV) m/z (%): 462 [M+]
(100), 464 [M+4] (31) Anal. Calcd. For C28H19N4ClO
(462.87):C, 72.72; H, 4.11; N, 12.12. Found: C, 72.74; H,
4.10; N, 12.14
9-(4-Chloro-phenyl)-7-phenyl-2-p-tolyl-7H-pyrazolo[3,4-h]
[1,6]naphthyridine (5f)
This compound was obtained as a pale yellow solid,
0.395 g (88%); mp 243–244°C; IR (KBr): 2919 m,
1
1612 s, 1512 scm−1; H NMR (CDCl3): δ 3.12 (s, 3H,
CH3), 7.30 (t, 1H, J=8.1 Hz, Ar-H), 7.34 (d, 2H, J =
8.4 Hz, Ar-H), 7.51 (t, 2H, J = 8.1 Hz, Ar-H), 8.02 (d, 1H,
J = 8.4 Hz, Ar-H), 8.26–8.30 (m, 4H, Ar-H), 8.31(d, 2H,
J = 8.6 Hz, Ar-H), 8.42 (d, 1H, J = 8.4 Hz, Ar-H), 8.66 (d,
2H, J = 8.6 Hz,Ar-H), 9.08 (s, 1H, Ar-H); MS (70 eV) m/z
(%): 446 [M+] (100), 448 [M+2] (29); Anal. Calcd. For
C28H19N4Cl (446.88): C, 75.33; H, 4.26; N, 12.55. Found:
C, 75.35; H, 4.24; N, 12.57.
9-(4-Chloro-phenyl)-2-(3,4-dimethoxy-phenyl)-7-phenyl-
7H-pyrazolo[3,4-h][1,6] naphthyridine(5j)
This compound was obtained as a silver needle,0.424 g
9-(4-Chloro-phenyl)-2-(,4-nitro-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6] naphthyridne (5g)
(86%); mp 242–243°C; IR (KBr): 3017 m, 2930 m, 1595 s,
1
1509 s, 1078 mcm−1; H NMR (CDCl3): δ 3.89 (s, 3H,
OCH3), 4.00 (s, 3H, OCH3), 7.05 (d, 1H, J=8.4 Hz, Ar-H),
7.45 (t, 1H, J=7.8 Hz, Ar-H), 7.56 (d, 2H, J = 7.8 Hz, Ar-
H), 7.62 (t, 2H, J = 7.8 Hz, Ar-H), 7.76 (dd, 1H, J=8.4 Hz
& J=2.1 Hz Ar-H), 8.01(d, 1H, J=8.7 Hz, Ar-H), 8.11 (d,
1H, J=2.1 Hz, Ar-H), 8.21 (d, 2H, J=8.6 Hz, Ar-H), 8.27
(d, 1H, J = 8.7 Hz, Ar-H), 8.39 (d, 2H, J = 8.6 Hz, Ar-H),
9.01 (s, 1H, Ar-H); MS (70 eV) m/z (%): 492 [M+] (100),
494 [M+2] (28); Anal. Calcd. For C29H21N4O2Cl (492.89):
C, 70.73; H, 4.26; N, 11.38. Found: C, 70.75; H, 4.24; N,
11.37.
This compound was obtained as a dark yellow solid,
0.427 g (89%); mp 250–251°C; IR (KBr): 2919 s, 1596 s,
1
1514 scm−1; H NMR (CDCl3): δ,7.21(d, 2H, J=8.7 Hz,
Ar-H), 7.30 (t, 1H, J = 8.1 Hz, Ar-H), 7.34 (d, 2H, J =
8.4 Hz, Ar-H), 7.51 (t, 2H, J = 8.1 Hz, Ar-H), 8.02 (d, 1H,
J = 8.4 Hz, Ar-H), 8.31(d, 2H, J = 8.6 Hz, Ar-H), 8.42 (d,
1H, J = 8.4 Hz, Ar-H),8.52 (d, 2H, J = 8.7 Hz, Ar-H), 8.66
(d, 2H, J = 8.6 Hz,Ar-H), 9.08 (s, 1H, Ar-H). MS (70 eV)
m/z (%): 477 [M+] (100), 479 [M+2] (28); Anal. Calcd. For

J Fluoresc (2011) 21:461–471
469
9-(4-Chloro-phenyl)-2-(2,5-dimethoxy-phenyl)-7-phenyl-
7H-pyrazolo[3,4-h][1,6] naphthyridine.(5k)
cm−1; 1H NMR (DMSO-d6): 7.29–7.37 (m, 5H, Ar-H), 7.56
(d, 2H, J=8.4 Hz, Ar-H), 7.98 (d, 2H, J = 8.4 Hz, Ar-H),
8.03 (d, 1H, J = 8.7 Hz, Ar-H), 8.28 (d, 2H, J = 8.6 Hz, Ar-
H) 8.49 (d, 2H, J = 8.6 Hz, Ar-H), 8.72 (d, 1H, J = 8.7 Hz,
Ar-H), 9.14 (s,1H, Ar-H); MS (70 eV) m/z (%): 510 [M+]
(68), 469 [M+2] (94), 471 [M+4] (31); Anal. Calcd. for
C27H16N4ClBr (511.77): C, 63.52; H, 3.13; N, 10.98.
Found: C, 63.55; H, 3.14; N, 10.96.
This compound was obtained as a silver solid, 0.430 g (87%);
mp 243–244°C; IR (KBr): 3004 m, 2941 m, 1602 s, 1501 s,
1078 mcm−1; 1H NMR (CDCl3): δ 3.81 (s, 3H, OCH3), 4.01
(s, 3H, OCH3), 6.76 (d, 2H, J=8.4 Hz, Ar-H), 6.89(dd, 1H,
J = 8.2 & J=2.3 Hz, Ar-H), 7.27(d, 1H, J=8.2 Hz, Ar-H),
7.34 (d, 2H, J=7.8 Hz, Ar-H), 7.42 (t, 1H, J=8.4 Hz, Ar-H),
7.52 (t, 2H, J=7.8 Hz, Ar-H), 7.54(d, 1H, J=2.3 Hz, Az-H),
7.64 (d, 1H, J=8.4 Hz, Ar-H), 8.34 (d, 2H, J=7.8 Hz, Ar-H),
8.62 (d, 1H, J=8.4 Hz, Ar-H), 9.08 (s, 1H, Ar-H); MS
(70 eV) m/z (%):492 [M+] (100), 494 [M+2] (28); Anal.
Calcd. for C29H21N4O2Cl (492.89): C, 70.73; H, 4.26; N,
11.38. Found: C, 70.75; H, 4.24; N, 11.37.
2,9-Bis(4-bromophenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]
naphthyridine(5o)
This compound was obtained as a pale brown solid,
0.478 g (86%); mp 249–250°C; IR (KBr): 2923 m,
1
1608 s, 1501 scm−1; H NMR (DMSO-d6): δ 7.25–7.32
(m, 3H, Ar-H), 7.46 (t, 4H, J=8.4 Hz, Ar-H), 7.74 (d, 2H,
J = 8.7 Hz, Ar-H), 8.02 (d, 1H, J = 8.7 Hz, Ar-H), 8.28 (d,
2H, J = 8.6 Hz, Ar-H) 8.49 (d, 2H, J = 8.6 Hz, Ar-H),
8.82 (d, 1H, J = 8.7 Hz, Ar-H), 9.16 (s, 1H, Ar-H); MS
(70 eV) m/z (%): 554 [M+] (48), 556 [M+2] (96), 558
[M+4] (46); Anal. Calcd. For C27H16N4Br2 (556.22): C,
58.48.; H, 2.88; N, 10.10. Found: C, 58.51; H, 2.87; N,
10.12
9-(4-Chloro-phenyl)-2-(2,4,6-trimethoxy-phenyl)-7-phenyl-
7H-pyrazolo[3,4-h][1,6] naphthyridine(5l)
This compound was obtained as a silver needle, 0.464 g
(88%); mp 247–248°C; IR (KBr): 3004 m, 2941 m, 1602 s,
1
1501 s, 1075 mcm−1; H NMR (CDCl3): δ 3.78 (s, 6H, 2×
OCH3), 3.89 (s, 3H, OCH3), 6.31 (s, 2H, Ar-H), 7.35 (t, 1H,
J=7.5 Hz, Ar-H), 7.51–7.57 (m, 3H, Ar-H), 8.23 (d, 2H, J =
7.5 Hz, Ar-H), 8.31 (d, 1H, J=8.4 Hz, Ar-H), 8.36(d, 2H, J =
8.6 Hz, Ar-H), 8.53(d, 2H, J = 8.6 Hz, Ar-H) 9.06 (s, 1H, Ar-
H); 13C NMR (CDCl3): δ 55.42, 55.90 (2C’s), 91.45 (2C’s),
117.77, 118.10, 121.17 (2C’s), 123.5 (2C’s), 124.53, 126.01,
127.5, 128.3 (2C’s), 129.09 (2C’s), 130.89, 136.05, 138.19,
139.05, 141.2, 143.67, 144.2, 146.29, 149.58, 150.23, 151.62
(2 C’s), 155.27. MS (70 eV) m/z (%): 522 [M+] (100), 524
[M+2] (29), Anal. Calcd. for C30H23N4O3Cl (522.88): C,
68.96; H, 4.40; N, 10.72. Found: C, 68.94; H, 4.41; N, 10.74.
9-(4-Bromo-phenyl)-2-(3,4-dichloro-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6] naphthyridne(5p)
This compound was obtained as a colorless solid, 0.474 g
(86%); mp 263–264°C; IR (KBr): 2930 m, 1612 s, 1508 s
cm−1; 1H NMR (DMSO-d6): δ 7.28 (d, 1H, J=8.4 Hz, Ar-
H), 7.47 (t, 1H, J=7.5 Hz, Ar-H), 7.59 (d, 2H, J = 7.5 Hz,
Ar-H), 7.63 (t, 2H, J = 7.5 Hz, Ar-H), 7.99 (dd, 1H, J=
8.4 Hz & J=2.3 Hz Ar-H), 8.21 (d, 1H, J=8.6 Hz, Ar-
H),), 8.52 (d, 1H, J=2.3 Hz, Ar-H), 8.64 (d, 2H, J=8.7 Hz,
Ar-H), 8.71 (d, 1H, J = 8.6 Hz, Ar-H), 8.80 (d, 2H, J =
8.7 Hz, Ar-H), 9.03 (s, 1H, Ar-H); MS (70 eV) m/z (%):
545 [M+] (71), 547 [M+2] (98), 549 [M+4] (64), 551
[M+6] (11); Anal. Calcd. for C27H15N4Cl2Br (546.32): C,
59.44; H, 2.75; N, 10.27. Found: C, 59.47; H, 2.78; N,
10.25.
9-(4-Bromo-phenyl)-2,7-diphenly-7H-pyrazolo[3,4-h][1,6]
naphthyridine(5m)
This compound was obtained as a pale yellow solid,
0.416 g (87%); mp 226–227°C; IR (KBr): 2925 m,
1
1591 s, 1500 scm−1; H NMR (CDCl3): 7.35 (t, 1H, J=
7.8 Hz, Ar-H), 7.51–7.62 (m, 5H, Ar-H), 8.01 (d, 1H, J=
8.4 Hz, Ar-H), 8.25 (d, 2H, J=7.8 Hz, Ar-H), 8.35 (d, 2H,
J=8.2 Hz, Ar-H), 8.42 (d, 1H, J = 8.4 Hz, Ar-H),8.45(d,
2H, J = 8.6 Hz, Ar-H),8.64(d, 2H, J = 8.6 Hz, Ar-H), 9.08
(s, 1H, Ar-H); MS (70 eV) m/z (%): 476 [M+] (96), 433 [M+
2] (88); Anal. calcd. for C27H17N4Br (477.32): C, 68.06.; H,
3.57; N, 11.76. Found: C, 68.09; H, 3.58; N, 11.72.
2-(2-Bromo-4-chloro-phenyl)-9-(4-Bromo-phenyl)-7-
phenyl-7H-pyrazolo[3,4-h][1,6] naphthyridine (5q)
This compound was obtained as a yellow solid, 0.521 g
(88%); mp 269–270°C; IR (KBr): 2930 m, 1595 s, 1503 s
cm−1; 1H NMR (DMSO-d6): δ 7.25(dd, 1H, J=8.4 &
2.6 Hz, Ar-H), 7.44 (t, 1H, J=7.5 Hz, Ar-H), 7.52 (d, 2H,
J = 7.5 Hz, Ar-H), 7.58 (t, 2H, J = 7.5 Hz, Ar-H), 7.78 (d,
1H, J=2.6 Hz Ar-H), 8.20(d, 1H, J=8.4 Hr, Ar-H), 8.26
(d, 1H, J = 8.6 Hz, Ar-H), 8.67 (d, 2H, J = 8.7 Hz, Ar-H),
8.73 (d, 1H, J = 8.6 Hz, Ar-H), 8.82 (d, 2H, J = 8.7 Hz,
Ar-H), 9.04 (s, 1H, Ar-H); MS (70 eV) m/z (%): 588 [M+]
9-(4-Bromophenyl)-2-(4-chlorophenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6]naphthyridine (5n)
This compound was obtained as a yellow solid, 0.454 g
(89%); mp 243–244°C; IR (KBr): 2924 s, 1610 s, 1500 s

470
J Fluoresc (2011) 21:461–471
(48), 590 [M+2] (100), 592 [M+4] (74), 594 [M+6] (19);
Anal. Calcd. for C27H15N4ClBr2 (590.67): C,55.10; H,
2.55; N, 9.52. Found: C, 55.14; H, 2.56; N, 9.54.
9-(4-Bromo-phenyl)-2-(4-methoxy-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6] naphthyridine (5u)
This compound was obtained as a silver needle, 0.425 g
(83%); mp 271–272°C; IR (KBr): 3022 m, 2919 m,
1610 s, 1501 s, 1070 mcm−1; 1H NMR (CDCl3): δ 3.93(s,
3H, OCH3), 7.19(d, 2H, J=8.7 Hz,Ar-H), 7.42(t, 1H, J=
7.6 Hz, Ar-H), 7.56(t, 2H, J = 7.6, Ar-H), 7.61(d, 2H, J =
7.6 Hz, Ar-H), 7.99(d, 1H, J=8.4 Hz, Ar-H), 8.28(d, 2H,
J = 8.7 Hz, Ar-H), 8.38(d, 2H, J = 8.6 Hz, Ar-H), 8.40(d,
1H, J = 8.4 Hz, Ar-H), 8.63(d, 2H, J = 8.6 Hz, Ar-H), 9.07
(s,1H, Ar-H). MS (70 eV) m/z (%): 506 [M+] (100), 508
[M+2] (92) Anal. Calcd. For C28H19N4BrO (507.32): C,
66.40; H, 3.75; N, 11.06. Found: C, 66.43; H, 3.77; N,
11.04.
9-(4-Bromo-phenyl)-7-phenyl-2-p-tolyl-7H-pyrazolo[3,4-h]
[1,6]naphthyridine (5r)
This compound was obtained as a brown needle, 0.420 g
(85%); mp 254–255°C; IR (KBr): 2919 m, 1596 s, 1510 s
1
cm−1; H NMR (CDCl3): δ 3.12 (s, 3H, CH3), 7.30 (t, 1H,
J=8.1 Hz, Ar-H), 7.34 (d, 2H, J = 8.4 Hz, Ar-H), 7.51 (t,
2H, J = 8.1 Hz, Ar-H), 8.02 (d, 1H, J = 8.4 Hz, Ar-H),
8.26–8.30 (m, 4H, Ar-H), 8.31(d, 2H, J = 8.6 Hz, Ar-H),
8.42 (d, 1H, J = 8.4 Hz, Ar-H), 8.66 (d, 2H, J = 8.6 Hz,Ar-
H), 9.08 (s, 1H, Ar-H); 13C NMR (CDCl3): δ 19.64,
115.24, 116.78, 120.17 (2 C’s), 123.55 (2 C’s), 124.38,
125.85, 126.32, 127.27 (2C’s), 128.90 (2C’s), 129.14
(2C’s), 131.22 (2C’s), 133.99, 135.20, 137.57, 138.96,
142.95, 144.10, 145.64, 148.52, 150.66, 158.97 MS
(70 eV) m/z (%): 490 [M+] (95), 492 [M+2] (87); Anal.
Calcd. For C28H19N4Br (491.33): C, 68.57; H, 3.87; N,
11.42. Found: C, 68.59; H, 3.86; N, 11.44.
9-(4-Bromo-phenyl)-2-(3,4-dimethoxy-phenyl)-7-phenyl-
7H-pyrazolo[3,4-h][1,6] naphthyridine(5v)
This compound was obtained as a silver solid, 0.469 g
(87%); mp 277–278°C; IR (KBr): 3017 m, 2930 m, 1598 s,
1
1509 s, 1078 mcm−1; H NMR (CDCl3): δ 3.89 (s, 3H,
OCH3), 4.00 (s, 3H, OCH3), 7.05 (d, 1H, J=8.4 Hz, Ar-H),
7.45 (t, 1H, J=7.8 Hz, Ar-H), 7.56 (d, 2H, J = 7.8 Hz, Ar-
H), 7.62 (t, 2H, J = 7.8 Hz, Ar-H), 7.76 (dd, 1H, J=8.4 Hz
& J=2.1 Hz Ar-H), 8.01(d, 1H, J=8.7 Hz, Ar-H), 8.11 (d,
1H, J=2.1 Hz, Ar-H), 8.21 (d, 2H, J=8.6 Hz, Ar-H), 8.27
(d, 1H, J = 8.7 Hz, Ar-H), 8.39 (d, 2H, J = 8.6 Hz, Ar-H),
9.01 (s, 1H, Ar-H); 13C NMR (CDCl3): δ 58.45, 59.32,
115.24, 116.78, 123.05, 124.38, 125.85, 126.17 (2 C’s),
127.27 (2 C’s), 129.14 (2 C’s), 131.22, 132.23 (2 C’s),
133.99, 134.26, 132.04, 135.20, 137.57, 138.96, 142.95,
145.64, 146.23, 147.23, 148.52, 150.66, 158.97. MS
(70 eV) m/z (%): 536[M+] (98), 538 [M+2] (90); Anal.
Calcd. For C29H21N4O2Br (537.32): C, 64.92; H, 3.91; N,
10.44. Found: C, 64.89; H, 3.94; N, 10.47.
9-(4-Bromo-phenyl)-2-(4-nitro-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6]naphthyridne (5s)
This compound was obtained as a dark brown solid,
0.460 g (88%); mp 274–275°C; IR (KBr): 2919 m,
1
1596 s, 1551 m, 1511 s, 1357 mcm−1; H NMR (CDCl3):
δ,7.21(d, 2H, J=8.7 Hz, Ar-H), 7.30 (t, 1H, J = 8.1 Hz,
Ar-H), 7.34 (d, 2H, J = 8.4 Hz, Ar-H), 7.51 (t, 2H, J =
8.1 Hz, Ar-H), 8.02 (d, 1H, J = 8.4 Hz, Ar-H), 8.31(d, 2H,
J = 8.6 Hz, Ar-H), 8.42(d, 1H, J = 8.4 Hz, Ar-H),8.52 (d,
2H, J = 8.7 Hz, Ar-H), 8.66 (d, 2H, J = 8.6 Hz, Ar-H),
9.08(s, 1H, Ar-H). MS (70 eV) m/z (%): 521 [M+] (93),
523 [M+2] (89); Anal. Calcd. For C27H16N5BrO2
(522.31): C, 62.18; H, 3.07; N, 13.43. Found: C, 62.21;
H, 3.11; N, 13.41.
9-(4-Bromo-phenyl)-2-(2,5-dimethoxy-phenyl)-7-phenyl-
7H-pyrazolo[3,4-h][1,6] naphthyridine (5w)
9-(4-Bromo-phenyl)-2-(3,4-diCF3-phenyl)-7-phenyl-7H-
pyrazolo[3,4-h][1,6] naphthyridine (5t)
This compound was obtained as a silver needle, 0.476 g
(88%); mp 275–276°C; IR (KBr): 3004 m, 2941 m, 1602 s,
1
This compound was obtained as a brown needles, 0.540 g
(88%); mp 248–249°C; IR (KBr): 2930 m, 1595 s, 1505 s
cm−1; 1H NMR (CDCl3): δ7.43(t, 1H, J=8.5 Hz, Ar-
H),7.54(t, 2H, J = 8.5 Hz, Ar-H), 7.61(d, 2H, J = 8.5 HZ,
Ar-H), 8.08(s, 1H, Ar-H), 8.11(d, 1H, J = 8.7 Hz, Ar-H),
8.37(d, 2H, J = 8.4 Hz, Ar-H), 8.41(d, 2H, J = 8.4 Hz, Ar-
H), 8.56(d, 1H, J = 8.7 Hz, Ar-H), 8.62(s, 2H, Ar-H), 9.11
(s, 1H, Ar-H) MS (70 eV) m/z (%): 612 [M+] (96), 614
[M+2] (90) Anal. Calcd. For C29H15N4F6Br (613.28): C,
56.86; H, 2.45; N, 9.15. Found: C, 58.88; H, 2.47; N,
9.14.
1501 s, 1078 mcm−1; H NMR (CDCl3): δ 3.81 (s, 3H,
OCH3), 4.01(s, 3H, OCH3), 6.76 (d, 2H, J=8.4 Hz, Ar-H),
6.89(dd, 1H, J = 8.2 & J=2.3 Hz, Ar-H), 7.27(d, 1H, J=
8.2 Hz, Ar-H), 7.34 (d, 2H, J=7.8 Hz, Ar-H), 7.42 (t, 1H,
J=8.4 Hz, Ar-H), 7.52 (t, 2H, J=7.8 Hz, Ar-H), 7.54(d, 1H,
J=2.3 Hz, Az-H), 7.64 (d, 1H, J=8.4 Hz, Ar-H), 8.34 (d,
2H, J=7.8 Hz, Ar-H), 8.62 (d, 1H, J=8.4 Hz, Ar-H), 9.08
(s, 1H, Ar-H); MS (70 eV) m/z (%): 536 [M+] (97), 538
[M+2] (90); Anal. Calcd. for C29H21N4O2Br (537.32): C,
64.92; H, 3.91; N, 10.44. Found: C, 64.89; H, 3.94; N,
10.47.

J Fluoresc (2011) 21:461–471
471
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9-(4-Bromo-phenyl)-2-(2,4,6-trimethoxy-phenyl)-7-phenyl-
7H-pyrazolo[3,4-h][1,6] naphthyridine(5x)
This compound was obtained as a silver solid, 0.495 g (87%);
7. Lu WB, Zhang LH, Ye XS, Su JC, Yu ZX (2006) Molecular
receptors for monosaccharide: di (pyridyl)naphthyridine and di
(quinolyl) naphthyridine. Tetrahedron 62:1806–1816
8. Van D, Joost TM (1996) Gram scale synthesis of Benzo [ghi]
perylene and coronene. J Org Chem 61(3):1136–1139
9. Chan L, Jin H, Stefanac T, Lavallee JF, Falardeau G, Wang W,
Bedard J, May S, Yuen L (1999) Discovery of 1, 6-Naphthyridin
as a Novel class of potent and selective human cytomegalovirus
inhibitors J. Med Chem 42:3023
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Sustituted 1, 6-naphthyrdines as human cytomegalovirus inhib-
itors: conformational requirements. Bioorg Med Chem Lett
18:2769
mp 281–282°C; IR (KBr): 3004 m, 2941 m, 1602 s, 1501 s,
1
1075 mcm−1; H NMR (CDCl3): δ 3.78 (s, 6H, 2 x OCH3),
3.89 (s, 3H, OCH3), 6.31 (s, 2H, Ar-H), 7.35 (t, 1H,
J=7.5 Hz, Ar-H), 7.51–7.57 (m, 3H, Ar-H), 8.23 (d, 2H,
J = 7.5 Hz, Ar-H), 8.31 (d, 1H, J=8.4 Hz, Ar-H), 8.36(d, 2H,
J = 8.6 Hz, Ar-H), 8.53(d, 2H, J = 8.6 Hz, Ar-H) 9.06 (s, 1H,
Ar-H); MS (70 eV) m/z (%): 566 [M+] (100), 568 [M+2]
(89), Anal. Calcd. for C30H23N4O3Br (567.30): C, 63.60; H,
4.06; N, 9.89. Found: C, 63.63; H, 4.02; N, 9.92.
Acknowledgment The authors thanks to CSIR & UGC, New Delhi,
for the financial assistance to this research project, and Principal, K. T.
H. M. College, Nashik - 422 002 for facilities.
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Huffman J, Chan L, Jin H, Rando RF (2000) Antiviral properties
of a series of 1, 6-Naphthyridine and 7, 8-dihydroisoquinoline
derivatives exhibiting potent activity against human cytomegalo-
virus. Antimicrob Agents Chemother 44:929
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LF, Lavoie E (2003) 5H-Dibenzo[c, h] 1, 6-naphthyridin-6-ones:
novel topoisomerase l-targeting anticancer agents with potent
cytotoxic activity. J Bioorg Med Chem 11:2061
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of pyrazolo [3, 4-b]pyridines and attachment of amino acids and
carbohydrates as linkers. J Heterocycl Chem 45:1281–1286
14. Jachak MN, Kendre DB, Toche RB (2007) Synthesis of novel
dipyrazolo [3, 4-b: 3, 4-d] pyridine and study of their fluorescence
behavior. Tetrahedron 63:11000–11004
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