CHAPTER 1shodhganga.inflibnet.ac.in/.../10603/81957/9/09_chapter1.pdf · 2018. 7. 8. · 6 N N H N...
Transcript of CHAPTER 1shodhganga.inflibnet.ac.in/.../10603/81957/9/09_chapter1.pdf · 2018. 7. 8. · 6 N N H N...
1
CHAPTER 1
Novel Synthesis of 4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]
pyridine-5-carbaldehyde, Pyrazolo[3,4-h][1,6]naphthyridines via
Friedlander Condensation and study of their Fluorescence Properties
In this chapter we, have reported the synthesis of pyrazolo[3,4-h][1,6]naphthyridines by
Friedlander condensation of 4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-
carbaldehyde with substituted acetophenones. The o-aminoaldehyde is synthesized by
multistep procedure starting from 5-aminopyrazole and diethylethoxymethylenemalona-
te. All new syntesized pyrazolo[3,4-h][1,6]naphthyridines were studided for their Fluore-
scence properties. Moreover, semi-emparical data of syntesized pyrazolo[3,4-h][1,6]nap-
hthyridines was calculated by MOPAC-2009/PM6 softwere and stuided the effect of sol-
vents and substetuent on Fluorescence behaviour of this compounds.
This chapter is divided into two sections A and B:
Section A: Novel syntesis of 4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-
carbaldehyde (o-aminoaldehyde) and pyrazolo[3,4-h][1,6]naphthyridines.
Section B: Stuided the effect of solvents and substetuent on Fluorescence behaviour of
pyrazolo[3,4-h][1,6]naphthyridines.
Section A: Novel syntesis of 4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-
carbaldehyde (o-aminoaldehyde) and pyrazolo[3,4-h][1,6]naphthyridines.
2
1.1. Introduction
Annulation reactions with hetrocyclic aminoaldehydes provides synthectic entry in to het-
rocyclic systems fused to a pyridine or pyrimidine nucleus by condensation reactions
with reactive methylenes. It was noted from literature [1, 2], that heterocyclic orthoamin-
oaldehydes are generally accessible from aminocarboxylic acid precursors 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 valu-
able synthetic method for heterocyclic aminoaldehyde, since the starting aminonitriles are
readily accessible [3].
Pyrazole derivatives and heterocycle-annulated pyrazoles have wide spectrum of interes-
ting agricultural and various biological activities [4-9]. Heterocycle-annulated naphthyr-
idine derivatives constitute an important class of compounds possessing diverse types of
biological properties such as α2-adrenoceptor antagonist [10], adenosine 3‟,5‟-cyclic pho-
sphate phosphodiesterase III inhibitors [11], antimicrobial [12], anti-inflammator [13,14].
Several reports are dedicated to naphthyridine chemistry [15, 16]. 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 [17, 18], but also as new
drug leaders [19, 20] and anticancer active screening agents in new drug discovery [21,
22].
Literature survey reveals the following two methods for the synthesis of
pyrazolo[3,4-h][1,6]naphthyridine derivatives
3
I) Pyridine ring annulated on pyrazolopyridine nucleus
II) Pyrazolo ring annulated on naphthyridine nucleus
I) Pyridine ring annulated on pyrazolopyridine nucleus
1) Y. Miki et. al. [23] reported the synthetic route used for the preparation of 2-methyl-4-
phenyl-2,3-dihydro-1H-pyrazolo[2,3,4-de][1,5]naphthyridine-2-oxides 7a,b. N-aminopy-
ridinium salt 2 was prepared from benzyl (pyridin-3-yl) methylcarbamate 1, which on
1,3-dipolar cycloaddition with 3-phenyl-2-propynal (3a: R = H; 3b: R = Ph) in the prese-
nce of potassium carbonate in acetonitrile gave pyrazolo[1,5-a]pyridines 4 (26%) and 5
(12%) after separation by column chromatography. Deprotection of 4 with 30% hydrogen
bromide-acetic acid solution followed by treatment with formaldehyde and sodium cyno-
borohydride gave the tricyclic amine (2-methyl-4-phenyl-2,3-dihydro-1H-pyrazolo[2,3,4-
de][1,5]naphthyridine) 6 in 86% yield. Similar, oxidation of the amine 6 with m-chlorop-
erbenzoic acid (m-CPBA) gave the desired N-oxide 7.
N
NHCO2CH
2Ph
NNH2
NHCO2CH
2Ph
NN
NHCO2CH
2Ph
COR
Ph NN
COR
NHCO2CH
2Ph
PhNH2OMes
CPh
CCOR
NN
N
Me
R
Ph
m-CPBA
NN
N
MeO
R
Ph
+
-OMes
+
12
3a-b
4a-b
4a-b
5a-b
6a-b
1) HBr, AcOH
2) HCHO,
NaBH3CN
a: R = H, b: R = Ph
7a-b
2) The pyrazolo[3,4-b][1,8]naphthyridine derivatives 13 in the treatment of Alzheimer‟s
disease as acetylcholinesterase inhibitors described by E. J. Barreiro et al [24]. The synt-
hesis of pyrazolo[3,4-b][1,8]naphthyridines 13 by classical synthetic methods, exploring
5-chloro-3-methyl-1-phenylpyrazole 8 [25] as the common key intermediate. Pyrazole
4
derivative 9 was regioselectively formylated at C4 using Vilsmeier-Hacck conditions
[25], followed by aza-functionalization of C5, exploring the nucleophilic SN2 displacem-
ent of chlorine atom by azide anion, catalyazed by the phase transfers agent tetrabutylam-
monium bromide (TBAB) [26]. Chemoselective reduction of the azide group of compou-
nd 10 by treatment with iron powder in acidic media [27] furnished o-aminoaldehyde
derivatives 11, which was converted into the corresponding pyrazolo[3,4-b]pyridine 12
through one pot Knovengel condensation of malononitrile with compound 11. The inter-
mediate 12 with cyclic ketones such as cyclopentanone or cyclohexanone using alumin-
um chloride as Lewis acid, to furnish the pyrazolonaphthyridines 13a,b.
NN
ClN
NCl
CHO
POCl3, DMF NaN
3, TBAB
DMSO, RT
Cyclohexanone or cyclopentanone
NN N
N
n
AlCl3, ClCH
2CH
2Cl, reflux
NN
CHO
N3 N
N
CHO
NH2
NN N
CN
NH2
Fe, NH4Cl
ACOEt/H2O
RT
CH2(CN)
2, Et
3N
MeOH, reflux
8 9 10 11
12(13a) n=0
(13b) n=113
3) M. N. Jachak et al [28] reported the synthesis of pyrazolo[3,4-b][1,6]naphthyridine 16
by the reaction of 5-amino-4-carbaldehydes 14 and N-benzyl-1-piperidone 15 in ethanolic
potassium hydroxide solution at reflux temperature.
NN
NH2
CHO
R
N
O
NN N
N
R
KOH, EtOH
Reflux
1416
15
5
4) A new potential antiviral heterocyclic scaffold, namely 3H-benzo[b]pyrazolo[3,4-h]-
[1,6]naphthyridines 23 designed by A. M. R. Bernardino et al [29]. A known synthetic
approach [30-32] was used for preparing the new 3H-benzo[b]pyrazolo[3,4-h][1,6]naph-
thyridine derivatives 23, starting from ethyl-4-chloro-1H-pyrazolo[3,4-b]-pyridine-5-car-
boxylate 20. Briefly, 20 were prepared from 5-aminopyrazoles 17, through condensation
with diethylethoxymethylenemaonlate 18 and cyclization, followed by reaction with anil-
ines, hydrolysis and a key step of „chlorocyclization‟ using phosphorus oxychloride [32-
35].
N
N
N
Cl
COOEt
R
Ph
NN
NH2
R
Ph NN
NH
H
OO
OEtEtOR
PhH
OEt
O
EtO
O
OEt
N
N
N
N
COOEt
R
Ph
HNH2
R1
N
N
N
NR
Ph
H
COOH
R1
N
N
N
NR
Ph
Cl
R1
NH
N
N
NR
Ph
O
R1
R1
20
21
+
17 18 19
POCl3
20% NaOH
22
POCl3
3 h
23
POCl3
23
1 h
II) Pyrazolo ring annulated onto naphthyridine nucleus
1) A. Da Settimo et al [36] achieved the synthesis and benzodiazepine receptor activity of
4,5-dihydro-1H-pyrazolo[4,3-c][1,8]naphthyridine derivatives 25 by the cyclocondensa-
tion of 2,3-dihydro-3-(hydroxymethylene)-5-substituted-1,8-naphthyridin-4(1H)-one 24
with various hydrazines.
6
N NH
N NAr
R
N NH
O OHR
ArNHNH2
24 25
2) P. Victory et al [37] synthesized pyrazolo[3,4-h][1,6]naphthyridine-5,9-diamines 30 by
starting with 2-dicyanomethylene-1,2-dihydropyridine-3-carbonitriles [38, 39] 26. The
cyclization was carried out in acetic acid with HCl and HBr both at room temperature and
at reflux to obtain 27 (when X = Cl) and 28 (when X = Br). The nucleophilic condensat-
ion of halogen with hydrazine hydrate (80 %) in dioxane at reflux yielded the same inter-
mediate hydrazino-substituted naphthyridines 29. The intramolecular cyclocondensation
of 29 in ethanol at reflux temperature afforded the pyrazolo[3,4-h][1,6]naphthyridine-5,9-
diamine 30.
NH
R2
R1
CN
CN
CN
NH
R2
R1
N
CN
X
NH2
NH
R2
R1
N
CN
NHNH2
NH2
NH
R2
R1
N
NH2
NH
NNH
2
26 27 (X = Cl)
28 (X = Br)
HX (X = Cl, Br) NH2NH2
29
EtOH, reflux
30
Dioxane, refluxAcOH
3) The novel pyrazolo[3,4-c][1,8]naphthyridin-4(5H)-one derivatives 36 that inhibit pho-
phodiesterase IV, or pharmaceutically acceptable salts presented by H. H. Kanazawa [40
]. The pyridine compound 31 was converted into pyrido[2,3-d][1,3]oxazine-2,4-dione 32
by the reaction with trichloromethyl chloroformate, which was further transformed into
1,8-naphthyridine 34 by the treatment with diethyl oxalate in presence of sodium hydride,
7
followed by basic hydrolysis with potassium hydroxide. The compound 34 was reacted
with acid chloride in polyphosphoric acid to produce compound 35, which on condensa-
tion with hydrazine derivatives to furnish pyrazolo[3,4-c][1,8]naphthyridin-4(5H)-one
derivatives 36.
N NH
O
N
O
O
ON N
OH
ON
COOEt
N
OH
ON
(CH2)nAr
O
NN O
OH
(CH2)nAr
N
NN O
N
R2
R1
R1
R1
R1
R1
R1
Cl3COCOClNaH
(COOEt)2
KOH
Ar(CH2)nCOCl
Polyphosphoric
acid
R2NHNH2
heat
31 32 33
34
5
35 36
1.2. Present Work
In the present work, we have reported the synthesis of new pyrazolo[3,4-h][1,6]naphthyr-
idine derivatives via Friedlander condensation starting from new synthone i.e. 4-Amino-
3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carbaldehyde (o-aminoaldehyde) 40.
The Friedlander condensation of o-aminoaldehyde 40 and acetophenones in basic reacti-
on condition gaves pyrazolo[3,4-h][1,6]naphthyridine derivatives 41. The synthesized py-
razolo[3,4-h][1,6]naphthyridines were further studied for their photophysical properties.
Thus, Retrosynthesis of 4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carb-
aldehyde 40 and pyrazolo[3,4-h][1,6]naphthyridine derivatives 41 are depicted in the
Scheme 1 and 2.
8
1) Retrosynthesis of 4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-Car-
baldehyde, 40
The oxidation of alcohol 39 could be done with manganese (IV) oxide to obtain o-
aminocarbaldehyde 40. The amino alcohol derivative 39 could be obtained by one pot
reduction of both azido and ester functionality in 38 using lithium aluminiumhydride.
The azido ester derivative 38 could be obtained by SNAr displacement of chlorine atom in
compound 37 by azido using NaN3.
N
N
N
Ar
Ph
37
383940
NH2
H
O
N
N
N
Ar
Ph
NH2
OH
N
N
N
Ar
Ph
N3
O
O
N
N
N
Ar
Ph
Cl
O
O
Scheme-1
2) Retrosynthesis of pyrazolo[3,4-h][1,6]naphthyridine derivatives, 41
Pyrazolo[3,4-h][1,6]naphthyridine derivatives 41 could be synthesized by Friedlander
condensation reaction of 4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carb-
aldehyde 40 with various acetophenones (Scheme 2).
9
N
N
N
Ar
Ph
NH2
H
O
40
N
N
N
Ar
Ph41
N
Ar'
Acetophenones
Scheme-2
1.3. Results and Discussion
The important key intermediate i.e. o-chloroester 37 were obtained by the reported litera-
ture method [41] from 5-aminopyrazoles 42 on condensation of EMME 43 at reflux tem-
perature in ethanol for 10 hrs. which afforded open chain pyrazole derivatives 44 (Exper-
iment No. 2, Page No. 37).
H
OEt
O
EtO
O
OEt
+
43 44a-b
reflux, 10 h
EtOH
NN
NH2
Ar
Ph
42 a-b
NN
NH
Ar
Ph
H
O O
EtO OEt
Comp. No. Ar
44a p-Cl C6H4
44b p-Br C6H4
Scheme-3
The subsequent cyclization of 44 using POCl3 yielded the o-choloester 37, an important
precursor for the synthesis of o-aminocarbaldehydes 40 (Experiment No. 3, Page No. 38).
NN
NH
Ar
Ph
H
O O
EtO OEt
N
N
N
Ar
Ph
Cl
O
O
44a-b 37a-b
reflux,9 h
POCl3
10
Comp. No. Ar
37a p-Cl C6H4
37b p-Br C6H4
Scheme-4
1.3.1. Synthesis of ethyl-4-azido-3-(4-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-
5-carboxylate, 38(a-b)
Nucleophilic aromatic substitution, in which the nucleophilie displaces a good leaving
group such as halide on an aromatic ring. Substitutions of the chloro group are versatile
precursor in synthetic chemistry. There are several literature reports [42-46] on the
displacement of the chloro by the azide in different solvents such as DMSO, DMF, N-me-
thylpyrrolidin-2-one (NMP). The chlorine atom in compound 37(a-b) becomes mobile
under the effect of the electron acceptor ester group on the adjacent carbon of the aroma-
tic ring and which fascilitates the displacement by the nucleophile such as azide.
38a-b
N
N
N
Ar
Ph
N3
O
O
N
N
N
Ar
Ph
Cl
O
O
37a-b
stirred, 3h
NaN3, DMF
Comp. No. Ar
38a p-Cl C6H4
38b p-Br C6H4
Scheme-5
Thus, the o-chloroester 37a, aromatic nucleophilic substitution by azido group proceeds
through addition elimination mechanism with sodium azide in DMF at 80-90oC. After
completion of reaction (TLC), residue was quenched with water and extracted with chlor-
oform. The solvent was evaporated under reduced pressure and obtained colorless solid
was purified by column chromatography. Then it was characterized by spectral and anal-
11
ytical data. The IR spectrum of this solid showed absorption bands at 2144 cm-1
of azide
and at 1727 cm-1
for carbonyl of the ester group. The 1H-NMR spectrum (CDCl3) of this
solid showed triplet at 1.43 ppm (J = 6.8 Hz) for three protons of methyl group and
quartet at 4.45 ppm (J = 6.8 Hz) for two protons of methylene group which corresponds
to ethyl group. The five aromatic protons appeared in between 7.23-7.55 ppm correspo-
nded to N-phenyl ring. Two doublets of p-substituted ring are appered at 7.80 and 8.21
(J = 8.4 Hz) ppm respectively. The singlet at 9.07 ppm for proton of pyridine ring (Spe-
ctrum No. 1, Page No. 12). The 13
C NMR spectrum (CDCl3) of this solid showed peak at
13.51 ppm for methyl carbons and 54.76 ppm for the methylene carbon of the ester
group. The C-N3 carbon observed at 136.32 ppm. The C5 carbon attached to ester group
was observed at 124.35 ppm. All six carbons of phenyl ring & six carbon of p-substit-
uted ring, attached to pyrazole ring and six carbons of halogen substituted aromatic ring
appeared between 119.91-140.58 ppm. The C3 carbon of pyrazole ring observed at
150.63 ppm. The C6 carbon of the pyridine ring appeared at 151.42 ppm. The ester car-
bonyl carbon appeared at 166.47 ppm. The molecular ion peak at 418 [M+], 420 [M+2]
is exactly matches to the molecular weight of the solid. On the basis of above spectral
and analytical data structure 38a was assigned to this compound i.e. ethyl-4-azido-3-(4-p-
chlorophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, 38a.
Analogously compound 38b was synthesized and characterized by IR, 1H NMR,
13C
NMR and elemental analysis (Experiment No. 4, page No. 39).
12
1.3.2. Synthesis of 4-Amino-3-(4-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-yl)-
methanol, 39(a-b)
Azides [47] have attracted much attention, not only as excellent protecting groups, but as
key intermediates for the synthesis of a large number of organic compounds such as nucl-
eosides, carbohydrates [48], N-containing heterocycles [49], like quinolines, quinazoli-
nes, benzodiazepines, lactams, cyclic amides etc. A variety of the reagents have been rep-
orted in the literature [50] for the reduction of azides, and the most prominent employed
were LiAlH4 [51], borohydrides [52, 53], hexamethyldisilathiane [54], triphenyl phosph-
ine [42, 55], SmI2 [56], In/NH4Cl [57], FeCl3/NaI [58], Zn/AlCl3, Zn/BiCl3 [59]. The ma-
jority of these methods has some shortcoming in relation to their general applicability,
selectivity, commercial availability and reaction conditions.
NN N
O
ON3
38a
Cl
Spectrum No. 1: 1H NMR Spectrum of Ethyl 4-azido-3-(4-chloro-phenyl)-1-
phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, 38a
13
As part of our research work towards the synthesis of annulated heterocycles, we have
planned to develop new method for the synchronous reduction of both azido and ester
groups of compound 38 in the one pot.
38a-b 39a-b
N
N
N
Ar
Ph
NH2
OH
N
N
N
Ar
Ph
N3
O
O
0 oC, rt, 4 h
LAH, THF
Comp. No. Ar
39a p-Cl C6H4
39b p-Br C6H4
Scheme-6
Thus, the reduction of both the azido and ester functionality (ortho to each other) of 38a
in one pot by lithium aluminiumhydride (LAH) in dry THF at 0oC -room temperature for
4 hrs. The reaction mass was quenched with saturated sodium sulfate solution and then
extracted with ethyl acetate. The solvent was removed under reduced pressure and solid
obtained was crystallized from ethanol. The colorless solid was characterized by IR, 1H,
13C NMR and elemental analysis. The IR spectrum of it showed band at 3479, 3369, 3302
cm-1
for NH2 and -OH groups. The band at 1727 and 2144 cm-1
in 38a for ester and azide
group were disappeared. The 1H-NMR spectrum (DMSO-d6) of this solid showed doublet
at 4.53 ppm for two protons of methylene group, the D2O exchangeable triplet at 5.04
ppm for one proton of –OH of hydroxylmethylene group. The broad singlet at 6.29 for
two protons of –NH2 and other signals are nearly identical as obtained in 38a (Spectrum
No. 2, Page No. 14). The molecular ion peak at 350 [M+], 352 [M+2] is exactly matches
to the molecular weight of the solid (Spectrum No. 3, Page No. 14). The elemental analy-
sis was in agreement with molecular formula C19H14N4OCl of 39a. On the basis of above
14
spectral and analytical data structure 39a was assigned to this compound i.e. 4-Amino-3-
(4-Chloro-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-yl)-methanol. Analogously
compound 39b was synthesized and characterized by IR, 1H NMR,
13C NMR and
elemental analysis (Experiment No. 5, page No. 41).
Spectrum No. 3: Mass Spectrum of 4-Amino-3-(4-phenyl)-1-phenyl-1H-pyrazol[3,4-b]
pyridine-5-yl)methanol, 39a
Spectrum No. 2: 1H NMR Spectrum of 4-Amino-3-(4-chloro-phenyl)-1-phenyl-1H-
pyrazol[3,4-b]pyridine-5-yl) methanol, 39a
NN N
NH2
OH
39a
Cl
NN N
NH2
OH
39a
Cl
15
1.3.3. Synthesis of 4-Amino-3-(4-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-car-
baldehyde, 40(a-b)
The oxidation of primary alcohol to aldehyde is a useful reaction in organic chemistry
and several methods are known [60-65]. According to the embodiment of the process for
the oxidation of the primary alcohol to the aldehyde containing other oxidizable groups
such as amino and easily oxidizable heterocycles, which remain wholly unchanged
throughout by the oxidiazing agent such as manganese(IV)oxide [66,67] and o-iodoxybe-
nzoic acid [68].
N
N
N
Ar
Ph
39a-b 40a-b
NH2
H
O
N
N
N
Ar
Ph
NH2
OH MnO2
Acetonitrile, RT
20 h
Comp. No. Ar
40a p-Cl C6H4
40b p-Br C6H4
Scheme-7
Hence, we have employed MnO2 as oxidizing agent for the oxidation of the o-aminoa-
lcohol 39a. The compound 39a was dissolved in acetonitrile and treated with manganese
(IV)oxide in acetonitrile at room temperature for 20 hrs. The dark brown colored solution
was filtered through celite. The solvent was removed from the colorless filtrate, furnished
a colorless solid which was purified by crystallization from ethanol. Then it was charact-
erized by spectral and analytical methods. The IR spectrum of this solid showed band at
3435 and 1658 cm-1
for NH2 and carbonyl group respectively. The 1H- NMR spectrum in
(DMSO-d6) showed the broad singlet at 6.65 for two protons of –NH2. The aromatic prot-
ons are appered in their respective region. (Spectrum No. 4, Page No. 17). The singlet of
16
pyridine ring protone is appered at 8.43 ppm and the aldehydic protone showd singlet at
9.75 ppm. 13
C-NMR spectrum (DMSO-d6) showed the C-NH2 carbon at 158.7 ppm.
The C5 carbon attached to aldehyde group was observed at 110.1 ppm. All six carbons
of phenyl ring & six carbon of p-substituted benzen ring, attached to pyrazole ring and
six carbons of halogen substituted aromatic ring appeared between 120.2-139.7 ppm.
The C3 carbon of pyrazole ring observed at 150.6 ppm. The C6 carbon of the pyridine
ring appeared at 152.5 ppm. The aldehyde carbonyl carbon appeared at 193.0 ppm
(Spectrum No. 5, Page No. 17). The molecular ion peak 348 [M+], 350 [M+2] is exactly
matches to the molecular weight of the solid. The eleme- ntal analysis was in agreement
with molecular formula C19H12N4OCl of compound 40a. On the basis of above spectral
and analytical data structure 40a was assigned to this compound i.e. 4-Amino-3-(4-
chloro-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carbaldehyde, Analogously comp-
ound 40b was synthesized and characterized by IR, 1H-NMR,
13C NMR and elemental
analysis (Experiment No. 6, page No. 42).
17
Spectrum No. 4: 1H NMR Spectrum of 4-Amino-3-(4-chloro-phenyl)-1-phenyl-1H-
pyrazol[3,4-b]pyridine-5-carbaldehyde, 40a
NN N
NH2
H
O
40a
Cl
NN N
NH2
H
O
40a
Cl
Spectrum No. 5: 13
C NMR Spectrum of 4-Amino-3-(4-chloro-phenyl)-1-phenyl-1H-
pyrazol[3,4-b]pyridine-5-carbaldehyde, 40a
18
1.3.4. Synthesis of 2-(alkyl/aryl)-9-(4-aryl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphth-
yridines, 41(a-x)
The construction of ring structures from ortho-substituted aminoaldehyde synthon has
wide applicability for the annulations of heterocyclic systems. This construction method
predominates the direction of ring growth and generally permits the direct and
regiospecific introduction of functional groups and/or substituents in the newly formed
heterocyclic ring. From literature it was noted that o-aminoaldehyde, the first and best
known member of this class of compounds has been utilized for synthesis of various
heterocycles [69-74]. o-Aminoaldehydes [75] have fascinating potentiality for annulation
of heterocyclic ring structures, which provide a synthetic entry in heterocyclic systems
fused to a pyridine or pyrimidine nucleus by Friedlander condensation reactions. These
are, also the key intermediates for the synthesis of various biologically active hetero-
cycles [76, 77]. The annulation of pyridine ring on to heterocyclic nucleus involves the
[4+2] cyclocondensation reaction [78]. The Friedländer condensation of o-aminoaldehy-
des with ketones is described to take place either with strong bases or acids as catalysts;
in special cases the ring closure can be observed without a catalyst at higher temperatures
(e.g. under microwave irradiation) [78], which prompted us to investigate the reaction
pathway of 4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carbaldehyde.
4-Amino-3-(4-aryl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carbaldehyde, 40 have been
used mainly for the annulations of pyridine units, and their reactions with activated meth-
ylene compounds provide a general synthetic entry into pyrazolo[3,4-h][1,6]naphthyrid-
ines under the base catalyzed reactions. In this condensation we have use KOH as a base.
19
N
N
N
Ar
Ph
41a-z
CH3
O
KOH/ EtOH
30 min, reflux
R1
45
N
N
N
Ar
Ph
40a-b
NH2
H
ON
R1
Comp. No. Ar
41a p-Cl C6H4
41b p-Br C6H4
Scheme-8
45 R1
a CH3
b C6H5
c 4-Cl-C6H4
d 4-Br-C6H4
e 3, 4-Di-Cl-C6H3
f 2-Br-4-Cl-C6H3
g 4-CH3-C6H4
h 4-NO2-C6H4
i 3,5-Di-CF3-C6H3
j 4-OMe-C6H4
k 3,4-Di-OMe-C6H3
l 2,4-Di-OMe-C6H3
m 2,4,6-Tri-OMe-C6H2
Thus, the Friedlander condensation of o-aminoaldehyde 40a with acetone 41a in
refluxing ethanolic potassium hydroxide solution for 30 min, it was observed that the
solid crystallized out from the yellow colored reaction mass at reflux temperature itself. It
was cooled to room temperature and isolated by filtration. The obtained solid was purify-
ied by crystallization from ethanol as pale yellow colored solid in 66 % yield. Then it was
characterized by spectral and analytical data. Analogously compounds 41b-z was synth
esized and characterized by spectral and analytical data, (Experiment No. 7, page No. 44)
20
for example the 1H-NMR spectrum (CDCl3) of 41s showed singlet at δ 3.93 ppm for
three protons of methoxy group. The two doublets at δ 7.98 and 8.30 ppm corres- ponded
to four protons of p-methoxy substituted ring of acetophenone. The two doublets at δ
8.18 and 8.40 ppm corresponded to ortho coupled two protons of newly anulated naphth-
yridine ring. The two doublets at δ 8.20 and 8.63 ppm corresponded to four proto- ns of
p-chloro-substituted ring respectively. The one proton of pyridine ring showed singlet at
δ 9.07 ppm. The five aromatic protons appeared between δ 7.40-7.61 ppm corresponded
to N-phenyl ring (Spectrum No. 6, Page No. 21). 13
C-NMR spectrum (CDCl3) showed the
–OCH3 carbon at 55.5 ppm. The carbons of newly anulated naphthyridine ring were
showed the C2 carbon observed at 139.1 ppm. The C3 carbon observed at 110.1 ppm.
The C4 carbon observed at 128.0 ppm. The C12 carbon observed at 131.0 & C13 at
126.8 ppm respectively. All other aromatic carbons of naphthyridine were appeared bet-
ween there respective region (Spectrum No. 7, Page No. 21). The molecular ion peak at
462[M+], 464[M+2] is exactly matches to the molecular weight of the solid. The elemen-
tal analysis was in agreement with molecular formula C28H19N4ClO of 41s. On the basis
of above spectral and analytical data structure 41s was assigned to this compound i.e. 9-
(4-Chloro-phenyl)-2-(4-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridi-
ne. It is noteworthy that the reactions in presence of KOH as a base were brought to com-
pletion in a very short time compared to piperidine as a base, may be due to steric and
electronic effect of substituted acetophenones.
21
Spectrum No. 7: 13
C NMR Spectrum of 9-(4-Chloro-phenyl)-2-(4-methoxy-phenyl)-7-
phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridine, 41j
Spectrum No. 6: 1H NMR Spectrum of 9-(4-Chloro-phenyl)-2-(4-methoxy-phenyl)-7-
phenyl-7H-pyrazolo[3,4-h][1,6] naphthyridine, 41j
NN N
41j
N
OMe
Cl
NN N
41j
N
OMe
Cl
22
Section B: Stuided the effect of solvents and substetuent on Fluorescence behaviour of
pyrazolo[3,4-h][1,6]naphthyridines.
1.4. Photophysical Properties
1.4.1. Phenomenon of Fluorescence
Fluorescence merely recognized as an „odd‟ physical or physic-chamical phenomenon.
However, during the last 50 years, the intrest and application of fluorescence molecules
has stedily, sometime even dramatically increased and now fluorescent dyes play a
central role in many aspect of modern life. Luminescence is the emittion of light from
any substance and occurs from electronically exited states. Luminescence is formally
divided in to two categories, fluorescence and phosphorescence, depending on the nature
of the excited state. In excited states, the electron in the excited orbital is paired (of
opposite spin) to the second electron in the ground-state orbital. Consequently, return to
the ground state is spin-allowed and occurs rapidly by emission of a photon. Fluorescence
typically occurs from aromatic molecules. Fluorescence spectral data are genrally prese-
nted as emission spectra. A fluorescence emission spectrum is a plot of the fluorescence
intensity versus wavelength (nanometers) or wavenumber (cm-1
).
1.4.1.1. Jablon’ski Diagram
The processes which occur between the absorption and emission of light are usually
illustrated by a Jablonski [79] digram. Jablonski digram are often used as the starting
point for discussing light absorption and emission. They exist in variety of forms, to illus-
trate various moleculer processes which can occur in excited states. Thes diagrams are
named after Professor Alexander Jablonski, who is regarded as a father of fluorescence
spectroscopy because of his many accomplishments, including his descriptions of conce-
23
ntration depolarization and his definition of the term “anisotropy” to describe the polari-
zed emission from solutions [80, 81]. A typical Jablonski digram is shown in fig. 1. The
singlet ground, first and second electronic state are depicted by S0, S1 and S2, respect-
tively.
Fig. 1. Jablonski diagram.
At each of these electronic energy levels the fluorophores can exist in a number of vibrat-
ional energy levels, denoted by 0, 1, 2, etc. absorption typically occurs from molec- ules
with the lowest vibrational energy. The larg energy diffrance between the S0 and S1
axcited state is too large for thermal population of S1 and it is for this reason we use light
and not heat to induce fluorescence. Following light absorption, several processes usually
occur. A fluorophore is usually excited to some higher vibrational level of either S1 or S2.
With a few rare exceptions, molecules in condensed phases rapidly relax to the lowest
24
vibreational level S1. Fluorescence emission generally results when light is emitted due to
a transition of the types S1→S0, i.e. from a vibrationally-relaxed singlets state to the
ground state. In contrast, phosphorescence occurs, when light emitted due to transition of
the type T1→S0, i.e. from a vibrationally-relaxed triplet state to the ground state [82, 83].
Phosphorescence is slow process while fluorescence is fast process in the luminescence
spectroscopy.
The electrons in excited state are presente in HOMO-LUMO orbitals, which are perpend-
icular to each other in excited state. In this situation, hence the electrons find difficulty to
come at ground state due to twisted geometry [82, 83]. The electrons in excited states are
in singlet state, release energy slowly in the form of fluorescence. Hence twisted geome-
try in excited state is the cause of fluorescence behavior of the molecules. This concept is
important hence we have calculated HOMO-LUMO energies by using MOPAC-2009
/PM6 software.
1.4.2. Semi-empirical study
The semi-empirical calculations of substituted bispyrazolopyridines as a new bulky elect-
ron doner acceptor system in their electronic state were described by the A. B. J. Parusel
et al. [84]. Bis pyrazolopyridines were characterized by the semi-empirical method (AMI
and PM3) and A. B. J. Parusel et al. observed that compounds with strong electron doner
groups (OMe) showed higher thermal stability, while compounds having strong electron
acceptor groups showed less thermal stability. The most important moleculer orbital
programs were invented such as MOPAC, MM2, PM3, PPP. In 1998, Johan A. Pople was
received Nobel prize in chemistry for his contribution in development of Gaussion 70/80
compounter programs. With this program, the chemist can calculate physical parameters
25
such as HOMO, LUMO energies of organic compounds. We also noted that the hetero-
cycles which are useful as organic light emitting dioded (OLED) should fluoresce
between 400-700 nm and HOMO/LUMO or „electron-hole‟ gap is in rang 2.7-3.0 eV i. e.
low gap [68, 85].
Thus, after successful syntesis of fluorescent pyrazolo[3,4-h][1,6]naphthyridines, we
have perform semi-imperical calculationals of HOMO-LUMO energies, electron hole
gape by using MOPAC-2009/PM6 (Version 8.331) [86, 87] to investigate the fluoresce-
nce properties of synthesized pyrazolo-naphthyridines 41(a-z) and results are sumarized
in Table 2. The theoretical model obtained by the energy optimization computational
programme by PM6 showed that fluorescence properties are depende on the HOMO-
LUMO energy GAP values of the compounds (Table 1). The 3D picture of the pyrazolo-
naphthyridines is depicted in Fig. 2.
We observed that there is more overlapping between the HOMO-LUMO energy for 41h,
41i, 41j, 41k, 41l, 41t, 41u, 41v, 41w and 41x which shows low gap value, which shows
red shift and high quantum yields (Table 2). 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 and lowering electron hole gap. The doner chromoph-
ores (-CF3,-OCH3 groups) on ring D plays an important role in increasing electron
density and lowering electron hole gap. On the other hand, HOMP-LUMO energies of
compounds 41g & 41s shows increase in GAP vlues due to presence of inductively and
mesomerically electron withdrawing chromophore (-NO2) i. e. Lower overlapping of
atomic orbitals, this shows blue shift and low quantum yields. It was also found that
inductive effect is more predominant than mesomeric effect. In this compound the
26
practical results obtained are in agreement with the HOMO-LUMO obtained by semi-
empirical PM6 methods.
Fig. 2. 3D picture of Pyrazolo[3, 4-h][1,6]naphthyridines 41s.
Table 1: The molecular electronic properties (HOMO-LUMO energy, GAP) of the
pyrazolo[3,4-h][1,6]naphthyridines 41(a-z)
Comp. Ar R
HOMO
(eV)
LUMO
(eV)
GAP
(eV)
R R1 R
2 R
3 R
4 R
5
41a Cl CH3 -8.760 -1.351 7.409
41b Br CH3 -8.806 -1.412 7.394
41c Cl H H H H H -8.719 -1.373 7.346
41d Br H H H H H -8.772 -1.369 7.403
41e Cl H H Cl H H -8.820 -1.480 7.340
41f Br H H Cl H H -8.859 -1.490 7.369
41g Cl H H Br H H -8.829 -1.499 7.330
41h Br H H Br H H -8.838 -1.528 7.310
41i Cl H Cl Cl H H -8.846 -1.607 7.230
41j Br H Cl Cl H H -8.921 -1.597 7.324
41k Cl Br H Cl H H -8.804 -1.463 7.341
41l Br Br H Cl H H -8.845 -1.473 7.372
41m Cl H H CH3 H H -8.700 -1.295 7.405
41n Br H H CH3 H H -8.736 -1.306 7.430
41o Cl H H NO2 H H -8.965 -1.885 7.080
27
Comp. Ar R
HOMO
(eV)
LUMO
(eV)
GAP
(eV)
R R1 R
2 R
3 R
4 R
5
41p Br H H NO2 H H -9.007 -1.893 7.114
41q Cl H CF3 H CF3 H -8.978 -1.805 7.173
41r Br H CF3 H CF3 H -8.992 -1.786 7.206
41s Cl H H OCH3 H H -8.657 -1.273 7.384
41t Br H H OCH3 H H -8.685 -1.283 7.400
41u Cl H OCH3 OCH3 H H -8.501 -1.311 7.170
41v Br H OCH3 OCH3 H H -8.502 -1.323 7.179
41w Cl OCH3 H H OCH3 H -8.507 -1.230 7.277
41x Br OCH3 H H OCH3 H -8.510 -1.243 7.267
41y Cl OCH3 H OCH3 H OCH3 -8.486 -0.968 7.518
41z Br OCH3 H OCH3 H OCH3 -8.512 -0.977 7.535
GAP = ELUMO-EHOMO
1.4.3. Fluorescence quantum yield of pyrazolo[3,4-h][1,6]naphthyridines, 41(a-z)
The fluorescence lift time and quantum yield are perhaps the most importen characteristic
of a fluorophore. Substances with a quantum yields, approaching to unity, such as rhoda-
mines, display the brightest emission. The meaning of the quantum yield and lifetime is
best represented by a simplified Jablonski diagram (Fig.1).
The fluorescence quantum yield ( F) is the number of emitted photons relative to the
number of absorbed photones. In other words the quatum yield gives the probability of
the exicited state being deactivated by non-radiative mechanism (fluorescence) rather
than by another. The measurements of the “absolute” quantum yiedls do require more
sophisticated instrumentation [88]. It is easier to determine the “relative” quantum yields
of a fluorophores by comparing it with quantum yield of reference standard. Most
common standards are cresyl violet, fluorescein, quinine sulfate, tryptophan, L-tyrosine
etc. We have determined the quantum yields of all compounds by using quinine sulphate
28
as reference standard. The relative quantum yields are generally determined by comp-
aring the wavelength-integrated intensity of an unknown sample to that of a satndard. The
fluorescence quantum yield of the unknown sample is calculated by using equation 1.
I
IR
ODR
OD
n2
nR2
Q = QR
……..Equation 1
Where Q is the quantum yield of unknown, I is the integrated intensity, n is the refractive
index, and OD is the optical density. The subscript R refer to the reference fluorophore of
known quantum yield. Thus, Fluorescence quantum yields of each compound were deter-
mined by standaed literature procedure using quinine sulphate as reference standard [83,
89] and are given in Table 2.
1.4.4. Effect of solvent
A varity of environmental facters affect fluorescence emission, including interactions
between the fluorophore and surrounding solvent molecules (dictated by solvent
polarity), other dissolved inorganic and organic compounds, temperature, pH and the
localized concentration of the fluorescent species. The effect of these parameters varies
widely from one fluorophore to another, but the absorption and emission spectra, as well
as quantum yields, can be heavily influenced by environmental variables. In fact, the high
degree of sensitivity in fluorescence is primarily due to interaction that occue in the local
environmental during the excited state lifetime. Thus, in this piece of work, we mainly
give emphasis on the study effect of solvent on absorption and fluorescence emission,
because solvents play an important role in physical and chemical processes. Solvent
effects are related to the nature and the extent of the solute-solvent interactions developed
in the solvation shell of the solute [90]. Organic mixed solvents are widely used as the
29
mobile phase in liquid chromatograph, capillary electrophoreses as a reaction medium.
Solvent mixtures have improved physical properties such as solvation power, density,
viscosity and refractive index compared with their neat solvents [91]. When the solute is
dissolved in a solvent, the solvent exerts a definite influence on the solute. This influence
depends on the nature of the solvent. This influence reflects changes in the absorption
and fluorescence spectrum [92] and this phenomenon is known as solvatochromism.
Solvatochromism is used to describe the pounced change in the position sometimes in
intensity of an absorption band, accompanying a change in the polarity of medium. The
preferential solvation phenomenon that is the selective enrichment of the certain solvent
component in the solvation shell of many physiochemical parameters measured in the
mixtures [93]. Hydrogen bonding plays an important role in the study of preferential
solvation and has been widely investigated because it is present in large variety of
chemical, biochemical and pharmacological events [94].
1.4.4.2. Study of photophysical properties of pyrazolo[3,4-h][1,6]naphthyridines
(41a-z) with respect to solvents and substituents
A. ABSORPTION SPECTRA
The absorption spectra (UV model- Shimadzu UV-1601 UV-VIS spectrophotometer) of
the synthesized pyrazolo[3,4-h][1,6]naphthyridine 41a-z (Table 2) were taken in non-
polar dichloromethane, polar aprotic acetonitrile and polar protic methanol solvents at
room temperature. All absorption band maxima are given in Table 2 and spectra for 41z
are shown in all three solvents in fig 3. In all pyrazolo[3,4-h][1,6]naphthyridines have
chromophore present on the substituted benzene ring i.e. on D ring. 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
30
from * 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.
B. 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. 7 (for 41z), the excitation of each molecule at their corresponding absorption band
of each substituted naphthyridine shows single emission band (RF-5301 PC Spectrofluor-
ophotometer) 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 acetonitrile). 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 intramolecular hydrogen bond interaction between solvent and solute. As 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 ( ref = 0.54 in 0.1M H2SO4) [95].
31
Table 2: The photophysical data for electronic absorption (UV Max.), fluorescence
(Em Max.) and quantum yield ( F) of pyrazolo[h][1,6]naphthyridine 41(a-z) in three
solvents (ca 10-3
) at room temp.
Comp. Solvents Abs. (nm) Emi. (nm) Quantum Yield ( f)
41a CH2Cl2 349 452 0.196
CH3CN 355 461 0.197
CH3OH 357 454 0.184
41b CH2Cl2 344 453 0.187
CH3CN 358 459 0.190
CH3OH 356 460 0.180
41c CH2Cl2 370 457 0.264
CH3CN 364 456 0.259
CH3OH 368 452 0.258
41d CH2Cl2 368 460 0.272
CH3CN 363 459 0.270
CH3OH 365 455 0.271
41e CH2Cl2 371 466 0.278
CH3CN 369 464 0.272
CH3OH 366 459 0.270
41f CH2Cl2 369 469 0.281
CH3CN 367 467 0.278
CH3OH 365 461 0.274
41g CH2Cl2 373 472 0.281
CH3CN 368 470 0.277
CH3OH 364 467 0.278
41h CH2Cl2 371 475 0.281
CH3CN 365 472 0.277
CH3OH 363 466 0.275
41i CH2Cl2 375 470 0.280
CH3CN 371 468 0.279
CH3OH 372 465 0.278
41j CH2Cl2 374 475 0.282
CH3CN 370 471 0.279
32
CH3OH 373 469 0.277
41k CH2Cl2 379 471 0.271
CH3CN 375 469 0.268
CH3OH 369 465 0.269
41l CH2Cl2 377 474 0.286
CH3CN 375 471 0.281
CH3OH 375 469 0.279
41m CH2Cl2 370 474 0.273
CH3CN 367 471 0.271
CH3OH 366 464 0.266
41n CH2Cl2 368 479 0.289
CH3CN 365 476 0.285
CH3OH 367 471 0.284
41o CH2Cl2 385 438 0.179
CH3CN 377 435 0.176
CH3OH 379 429 0.174
41p CH2Cl2 371 441 0.185
CH3CN 368 437 0.181
CH3OH 369 433 0.179
41q CH2Cl2 377 488 0.330
CH3CN 371 484 0.327
CH3OH 372 481 0.328
41r CH2Cl2 374 491 0.326
CH3CN 370 489 0.325
CH3OH 369 485 0.322
41s CH2Cl2 373 467 0.277
CH3CN 370 466 0.275
CH3OH 370 463 0.273
41t CH2Cl2 376 477 0.284
CH3CN 371 475 0.283
CH3OH 371 470 0.280
41u CH2Cl2 379 477 0.295
33
CH3CN 374 473 0.288
CH3OH 374 461 0.281
41v CH2Cl2 372 484 0.309
CH3CN 368 481 0.307
CH3OH 369 472 0.298
41w CH2Cl2 378 473 0.281
CH3CN 370 469 0.279
CH3OH 373 460 0.271
41x CH2Cl2 375 479 0.292
CH3CN 371 477 0.289
CH3OH 369 466 0.277
41y CH2Cl2 379 490 0.339
CH3CN 377 487 0.324
CH3OH 377 455 0.298
41z CH2Cl2 376 495 0.345
CH3CN 371 487 0.338
CH3OH 373 458 0.284
The fluorescence quantum yield of these studied systems were 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 [96].
Fuether it was noted that halo-substituted molecules have less fluorescence quantum
yield as compared to methoxy substituted compounds. This may be due to qienching of
fluorescence with halogen atoms as the substituent. Pyrazolonaphthyridine 41u, 41v, 41w
and 41x having donor chromophores e.g. C4-OCH3, C3 & C4-di-OCH3, C2 & C5-di-
OCH3, C2, C4 & C6-tri-OCH3 on phenyl ring (ring-D) showed absorption and emission
maxima at 477 nm, 484 nm, 479 nm and 495 nm and quantum yields ( F) 0.248, 0.309,
0.292 and 0.345 respectively. Compound 41s having acceptor chromophore e.g. C4-NO2
34
on phenyl ring (ring-D) showed large decrease in emission maxima at 441 nm and quant-
um yield ( F) 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. 3: Absorption and Emission Spectra of compound 41z.
35
1.5. Conclusion
In conclusion, we have syntesized novel o-aminoaldehyde 40(a-b) and uitilized for synt-
hesis of novel anguler pyrazolo[3,4-h][1,6]naphthyridine derivatives by Friedlander con-
densation with diffrent substituted acetophones. These intresting pyrazolo[3,4-h][1,6]na-
phthyridine 41(a-z) were studied for their photophysical properties in protic and aprotic
solvents. It was observed that quantum yield of compounds is solvent dependent and
gretly influenced by the nature of substituent present on ring D ( newly annulated benze-
ne ring on pyridine ring). Thus, pyrazolonaphthyridines bearing electron-releasig group
i.e. substituents like di-CF3 and -OCH3 on ring D show relatively higher enviroment sens-
itive fluorescence properties as compared with the electron-withdrawing group like -NO2
on ring D at the para position. From these studies, we revels that pyrazolo[3,4-h][1,6]-
naphthyridine which low electron hole gape values shows high emission as well as high
quantum yield, while compounds have larger electron hole gap show low quantum yields
and are in agreement with theoretical observations. This study has brought out ine-resting
substiuents as well as solvent dependent fluorescence properties of pyrazolonaph-
thyridines. The efficent blue light emission, physical and chemical stability makes pyraz-
olonaphthyridine derivatives as a promising family of materials which may be useful in
photophysical applications. All these syntesized compounds are addition to library of flu-
orescence heterocyclic compounds.
36
1.4. Experimental Section
Experiment No. 1
Synthesis of 3-(4-Halophenyl)-1-phenyl-1H-pyrazole-5-amine (42)
Ar
O
CN
Ph-NH-NH2
EtOH
AcOH NN
NH2
Ar
Ph
+
46 a-b
42 a-b
Comp. No. Ar
42a p-Cl C6H4
42b p-Br C6H4
General Procedure: To the clear solution of p-substituted benzoylacetonitriles 46a (17.9
g, 0.1 mole) or 46b (22.2 g, 0.1 mol) and phenyl hydrazine (9.8 ml, 0.1 mole) in ethanol
(100 ml), acetic acid (15 ml) was added and the reaction mixture was refluxed for two
hours (TLC check). Solid obtained on cooling was filtered, dried and crystallized from
ethanol afforded compounds 42 in very good yield.
3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-5-amine (42a)
m.p. 190 oC Lit
67 m.p. 193
oC, Yield: 79%, (21.2g)
3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-5-amine (42b)
m.p. 203 oC Lit
67 m.p. 205
oC, Yield: 80%, (25.1g)
37
Experiment No. 2
Synthesis of Diethyl 2-((3-(Aryl)-1-phenyl-1H-pyrazol-5-ylamino)methylene)malon-
ate (44).
H
OEt
O
EtO
O
OEt
+
43 44a-b
reflux, 10 h
EtOH
NN
NH2
Ar
Ph
42 a-b
NN
NH
Ar
Ph
H
O O
EtO OEt
Comp. No. Ar
44a p-Cl C6H4
44b p-Br C6H4
General Procedure: A solution of 5-aminopyrazole 42a (2.69 g, 0.01 mol) or 1b (3.14 g,
0.01 mol) and diethylethoxymethylenemalonate 43 (2.00 mL, 0.01 mole) in absolute
ethanol (30 mL) was refluxed for 10 hours until the starting material had disappeared
(TLC check). The solid formed on cooling was filtered by suction, washed with ethanol
(10 mL) and dried at 60 oC and recrystallized from ethanol to afford colorless needles of
44 in good yields.
Diethyl-2-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-5-ylamino)methylene)malonate
(44a): Yield: 90 %, m.p. 115 o
C. IR (KBr): 3145, 2983, 1691, 1643, 1552, 1444, 1384,
839 cm-1
. 1H NMR (CDCl3): = 1.28 (m, 6H, 2CH3), 4.21 (m, 4H, 2CH2), 6.49 (s, 1H,
C4H), 7.37 (d, J = 8.4 Hz, 2H, ArH), 7.44 (m, 5H, ArH), 7.76 (d, J = 8.4 Hz, 2H, ArH),
8.22 (d, J = 12.6 Hz, 1H, C7H), 11.03 (d, J = 12.6 Hz, 1H, NH). Anal. Calcd. for
C23H22ClN3O4 (439.89) : C 62.80, H 5.03, N 9.54; Found. C 62.98, H 5.22, N 9.28.
Diethyl-2-((3-(4-bromophenyl)-1-phenyl-1H-pyrazol-5-ylamino)Methylene)malonate
(44b): Yield: 92 %, m.p. 122-124 oC. IR (KBr): 3036, 2970, 1680, 1633, 1545, 1441,
38
1384, 954, 825 cm-1
. 1H NMR (CDCl3): = 1.29 (m, 6H, 2CH3), 4.25 (m, 4H, 2CH2),
6.51 (s, 1H, C4H), 7.38 (d, J = 8.4 Hz, 2H, ArH), 7.45 (m, 5H, ArH), 7.77 (d, J = 8.4 Hz,
2H, ArH), 8.20 (d, J = 12.6 Hz, 1H, C7H), 11.01 (d, J = 12.6 Hz, 1H, NH). Anal. Calcd.
for C23H22BrN3O4 (484.34) : C 57.04, H 4.57, N 8.67; Found. C 57.30, H 4.81, N 8.39.
Experiment No. 3
Synthesis of Ethyl-4-chloro-3-(Aryl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbox-
ylate (37a-b).
NN
NH
Ar
Ph
H
O O
EtO OEt
N
N
N
Ar
Ph
Cl
O
O
44a-b 37a-b
reflux,9 h
POCl3
Comp. No. Ar
37a p-Cl C6H4
37b p-Br C6H4
General Procedure: A solution of 44a (4.398 g, 0.01 mol) or 44b (4.843 g, 0.01 mol)
and phosphorousoxychloride (35 mL) was refluxed for 9 hours until the starting material
had disappeared (TLC check). Then the solution was allowed to cool to room temperature
and then drop wise poured to crushed ice with constant stirring. The obtained solid was
filtered by suction, many times washed with cold water (250 mL), dried and recrystalized
from ethanol to afford 37a in 70 and 37b in 71 % yield.
Ethyl-4-chloro-3-(4-chlorophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
(37a): Yield 70 %, m.p. 170 – 172 oC, IR (KBr): 1733, 1581, 1552, 1458, 1363, 1288,
937, 844 cm-1
. 1H NMR (CDCl3): = 1.43 (t, 3H, CH3), 4.43 (q, 2H, CH2), 7.38 (m, 5H,
39
ArH), 7.68 (d, J = 8.4 Hz, 2H, ArH), 8.19 (d, J = 8.4 Hz, 2H, ArH), 9.05 (s, 1H, C6H).
13C NMR (CDCl3): = 14.8, (Me of ester), 58.7 (OCH2 of ester), 107.2, 120.5, 125.2,
126.8, 128.9, 129.4, 129.8, 131.5, 134.4, 139.8, 140.3, 145.8, 150.7, 151.3, 168.9 (ester
C=O). Anal. Calcd. for C21H15Cl2N3O2 (412.27) : C 58.91, H 3.50 N, 9.81; Found. C
58.66, H, 3.35, N 10.07.
Ethyl-3-(4-bromophenyl)-4-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
(37b): Yield 71 %, m.p. 180 – 182 oC. IR (KBr) 1725, 1563, 1435, 1343, 1285, 1235,
935, 834 cm-1
. 1H NMR (CDCl3): = 1.44 (t, 3H, CH3), 4.46 (q, 2H, CH2), 7.33 (m, 5H,
ArH), 7.67 (d, J = 8.4 Hz, 2H, ArH), 8.20 (d, J = 8.4 Hz, 2H, ArH), 9.02 (s, 1H, C6H).
13C NMR (CDCl3): = 14.7 (Me of ester), 58.8 (OCH2 of ester), 108.2, 119.4, 125.3,
126.9, 127.8, 129.5, 129.7, 131.4, 134.9, 138.5, 140.6, 144.8, 151.4, 152.2, 169.2 (ester
C=O). Anal. Calcd. for C21H15BrClN3O2 (456.72): C 55.24, H 3.28, N 9.19; Found. C
55.10, H, 3.54, N 9.05.
Experiment No. 4
Synthesis of ethyl-4-azido-3-(4-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carb-
oxylate, 38.
38a-b
N
N
N
Ar
Ph
N3
O
O
N
N
N
Ar
Ph
Cl
O
O
37a-b
stirred, 3h
NaN3, DMF
Comp. No. Ar
38a p-Cl C6H4
38b p-Br C6H4
40
General Procedure: A solution of 37a (4.122 g, 0.01 mol) or 37b (4.567 g, 0.01 mol)
sodium azide (0.650 g, 0.01 mol) in DMF (35 mL) was stirred at 80-90oC for 3 hrs. After
completion of reaction (TLC check), residue was poured in to cold water (50 mL) and
stirred for 30 min. and extracted with chloroform. The organic solvent was evaporated
under reduced pressure and obtained solid was purified by column chromatography using
toluene: acetone as the eluent in 9:1 ratio afforded a colorless solid 38a in 61 % and 38b
in 60 % yield.
Ethyl-4-azido-3-(4-chlorophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
(38a): Yield 61%, mp. 187-188 oC. IR (KBr): 2991, 2922, 2854, 2144, 1727, 1585,
1498, 1269, 1134, 910 cm-1
; 1H NMR (CDCl3): = 1.43 (t, 3H, CH3), 4.45 (q, 2H,
OCH2), 7.23-7.55 (m, 5H, Ar-H), 7.80 (d, J = 8.4 Hz, 2H, Ar-H), 8.21 (d, J = 8.4 Hz, 2H,
Ar-H ), 9.07 (s, 1H, C6-H). 13
C NMR (CDCl3): 14.1, 60.8, 105.3, 120.2, 125.4, 126.2,
128.4, 128. 7, 129.3, 129.4, 134.2, 135.7, 139.7, 144.2, 148. 9, 150.2, 167.6. Anal. Calcd.
for C21H15ClN6O2 (418.84) : C 60.22, H 3.61, N 20.07; Found. C 60.48, H 3.34, N 20.32.
Ethyl-4-azido-3-(4-bromophenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
(38b): Yield 60 %, mp. 191-192 oC. IR (KBr): 2958, 2912, 2314, 1700, 1515, 1445,
1134, 912 cm-1
. 1H NMR (CDCl3): = 1.42 (t, 3H, CH3), 4.43 (q, 2H, OCH2), 7.21-7.51
(m, 5H, Ar-H), 7.81 (d, J = 8.4 Hz, 2H, Ar-H), 8.22 (d, J = 8.4 Hz, 2H, Ar-H), 9.07 (s,
1H, C6-H). 13
C NMR (CDCl3): 14.2, 60.0, 106.3, 120, 125, 126.2, 128, 128.4, 129,
129.1, 133.6, 134.3, 138.5, 144.1, 147.5, 152, 168.6. Anal. Calcd. for C21H15BrN6O2
(462.29): C 54.44, H 3.26, N 18.14; Found. C 54.19, H 3.50, N 18.30.
41
Experiment No. 5
Synthesis of 4-Amino-3-(4-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-yl)–metha-
nol, 39.
38a-b 39a-b
N
N
N
Ar
Ph
NH2
OH
N
N
N
Ar
Ph
N3
O
O
0 oC, rt, 4 h
LAH, THF
Comp. No. Ar
39a p-Cl C6H4
39b p-Br C6H4
General Procedure:
A solution of 38a (4.180 g, 0.01 mol) or 38b (4.632 g, 0.01 mol) in tetrahydrofuran (15
ml) was added slowly into the dispersed Lithium-Aluminium-Hydride (LAH) (1.14 g,
0.03 mol) in tetrahydrofuran (20 ml) at 0oC, then the reaction mass was allowed to warm
up to 25oC and stirred it for 4 hrs. (TLC check). The reaction mass was quenched with
saturated sodium sulfate solution (20 ml) at 0oC and extracted in ethyl acetate (2 x 20
ml). The combined organic layer was washed with water (2 x 15 ml), dried over anhydri-
ous sodium sulfate, filtered, the solvent was removed under reduced pressure and crystal-
lized from ethanol to afforded 39a 77 % ans 39b in 76 % yield.
4-Amino-3-(4-Cl-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-yl)-methanol (39a):
Yield 3.22 g, 77 %, mp 188-189 oC. IR (KBr): 3479 (s), 3369 (m), 3302 (m), 2964 (m),
2144 (s), 1727 (s) cm-1
. 1H 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,
42
1H, Ar-H), 8.26 (d, 2H, J = 7.4 Hz, Ar-H), 8.30 (d, 2H, J = 7.5 Hz Ar-H). 13
C 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, 65.41; H, 4.23; N, 15.77.
4-Amino-3-(4-Br-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-yl)-methanol (39b):
Yield 3.18 g, 76 %, mp 185-186 oC. IR (KBr): 3479 (s), 3369 (m), 3302 (m), 2964 (m),
2144 (s), 1727 (s) cm-1
. 1H 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), 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). 13
C 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 (%) : 393
[M+] (89), 395 [M+2] (95). Anal. Calcd. for C19H14N4OBr (394.20) : C, 58.01; H, 3.56;
N, 14.24. Found: C, 58.19; H, 3.82; N, 14.49.
Experiment No. 6
Synthesis of 4-Amino-3-(4-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carbaldeh-
yde, 40.
N
N
N
Ar
Ph
39a-b 40a-b
NH2
H
O
N
N
N
Ar
Ph
NH2
OH MnO2
Acetonitrile, RT
20 h
43
Comp. No. Ar
40a p-Cl C6H4
40b p-Br C6H4
General Procedure:
Manganese(IV)dioxide (2.58 g) was added into the solution of 39a (3.508 g, 0.01 mol) or
39b (3.952 g, 0.01 mol) in acetonitrile (35 ml) or dichloromethane (35 mL) at 25oC for 20
hrs. After completion of reaction (TLC check). The reaction mass was filtered through
celite and solvent was removed under reduced pressure. The crude solid obtained was
washed with methanol, filtered, dried under high vacuum and recrystalised from ethanol:
DMF (8:2) to gives 40a in 93% and 40b in 90% yield as a pale yellow solid.
4-Amino-3-(4-Cl-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carbaldehyde (40a):
Yield 3.28 g, 93 %, mp 181-182 oC. 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), 7.29-7.78
(m, 5H, Ar-H), 8.08 (d, 2H, J = 8.6 Hz, Ar-H) 8.20 (d, 2H, J = 8.6 Hz Ar-H), 8.43 (s, 1H,
Ar-H), 9.75 (s, 1H, -CHO). 13
C 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 (70eV)
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, 65.76; H, 3.21; N, 16.25.
4-Amino-3-(4-Br-phenyl)-1-phenyl-1H-pyrazol[3,4-b]pyridine-5-carbaldehyde (40b):
Yield 3.11 g, 90 %, mp 184-185 oC. 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), 7.29-7.78
(m, 5H, Ar-H), 8.08 (d, 2H, J = 8.4 Hz, Ar-H), 8.20 (d, 2H, J =8 .4 Hz Ar-H), 8.43 (s,
1H, Ar-H), 9.75 (s, 1H, CHO). 13
C 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
44
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, 58.57; H, 3.20; N, 14.02.
Experiment No. 7
Synthesis of 2-(alkyl/aryl)-9-(4-aryl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridi-
ne, 41.
N
N
N
Ar
Ph
41a-z
CH3
O
KOH/ EtOH
30 min, reflux
R1
45
N
N
N
Ar
Ph
40a-b
NH2
H
ON
R1
Comp. No. Ar
41a p-Cl C6H4
41b p-Br C6H4
45 R1 45 R
1
a CH3 h 4-NO2-C6H4
b C6H5 i 3,5-Di-CF3-C6H3
c 4-Cl-C6H4 j 4-OMe-C6H4
d 4-Br-C6H4 k 3,4-Di-OMe-C6H3
e 3, 4-Di-Cl-C6H3 l 2,4-Di-OMe-C6H3
f 2-Br-4-Cl-C6H3 M 2,4,6-Tri-OMe-C6H2
g 4-CH3-C6H4
General Procedure:
A solution of 40a (0.348 g, 0.001 mol) or 40b (0.393 g, 0.001 mol), alkyl/aryl ketones 45
(0.001 mol) and ethanolic potassium hydroxide solution (15 mL, 2%) was heated under
reflux for 25-30 min. (TLC check). The reaction mass was cooled to room temperature,
45
the obtained solid was collected by suction filtration, washed and recrystalised with
ethanol to furnish compound 41 in 80-90 % yield as a colorless solid.
9-(4-chlorophenyl)-2-methyl-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridine (41a):
Yield 0.305 g (82%). mp: 177-178 oC. IR (KBr): 2929, 1622, 1508, 1423 cm
-1.
1H NMR
(300 MHz, CDCl3): δ, 2.82 (s, 3H, CH3), 7.37 (d, 1H, J = 7.4 Hz, Ar-H), 7.35-7.58 (m,
5H, Ar-H), 8.21 (d, 1H, J = 7.4 Hz, Ar-H), 8.26 (d, 2H, J = 8.4 Hz, Ar-H), 8.54 (d, 2H, J
= 8.4 Hz, Ar-H), 8.82 (s, 1H, Ar-H) ppm. MS: m/z (%) 370 [M+] (100), 372 [M+2] (31).
Anal. Calcd. for C22H15N4Cl (370.84): C, 71.24; H, 4.07; N, 15.10. Found: C, 71.50; H,
4.24; N, 15.30.
9-(4-Bromophenyl)-2-methyl-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridine (41b):
Yield 0.342 g (82%). mp: 180-181 oC. IR (KBr): 2929, 1622, 1508, 1423 cm
-1.
1H NMR
(300 MHz, CDCl3): δ, 2.82 (s, 3H, CH3), 7.37 (d, 1H, J = 7.4 Hz, Ar-H), 7.35-7.58 (m,
5H, Ar-H), 8.21 (d, 1H, J = 7.4 Hz, Ar-H), 8.26 (d, 2H, J = 8.4 Hz, Ar-H), 8.54 (d, 2H, J
= 8.4 Hz, Ar-H), 8.82 (s, 1H, Ar-H) ppm. MS: m/z (%) 415 [M+] (100), 417 [M+2] (93).
Anal. Calcd. for C22H15N4Br (415.30): C, 63.62; H, 3.63; N, 13.48. Found: C, 63.39; H,
3.88; N, 13.74.
9-(4-Chloro-phenyl)-2,7-diphenly-7H-pyrazolo[3,4-h][1,6]naphthyridine (41c):
Yield 0.388 g (89%). mp 212-213 oC. IR (KBr): 2925 m, 1610 s, 1510 s cm
-1.
1H 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, 75.20; H, 3.68; N, 12.71.
46
9-(4-Bromo-phenyl)-2,7-diphenly-7H-pyrazolo[3,4-h][1,6]naphthyridine (41d):
Yield 0.416 g (87%). mp 226-227 oC. IR (KBr): 2925 m, 1591 s, 1500 s cm
-1;
1H 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, 68.29; H, 3.31; N, 11.98.
2,9-Bis(4-chloro-phenyl)-7-diphenyl-7H-pyrazolo[3,4-h][1,6]naphthyridine (41e):
Yield 0.404 g (86 %). mp 235-236 oC. 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, 69.66; H, 3.22; N, 11.78.
9-(4-Bromophenyl)-2-(4-chlorophenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridine
(41f): Yield 0.454 g (89 %). mp 243-244 oC. IR (KBr): 2924s, 1610s, 1500s 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, 63.79; H, 3.27; N, 10.82.
2-(4-Bromophenyl)-9-(4-chloro-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridi-
ne (41g): Yield 0.440 g (86 %). mp 247-248 oC. IR (KBr): 2923 m, 1608 s, 1501 s cm
-1.
47
1H 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 (%): 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, 63.30; H, 3.41; N, 10.73.
2,9-Bis(4-bromophenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridine (41h):
Yield 0.478 g (86 %). mp 249-250 oC. IR (KBr): 2923 m, 1608 s, 1501 s cm
-1.
1H 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, 58.72; H, 3.10; N, 10.26.
9-(4-Chloro-phenyl)-2-(3,4-dichloro-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphth-
yridne (41i): Yield 0.435 g (87 %). mp 252-253 oC. IR (KBr): 2930 m, 1614 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 (%): 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, 64.90; H, 3.22; N, 11.47.
9-(4-Bromo-phenyl)-2-(3,4-dichloro-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphth-
yridne (41j): Yield 0.474 g (86 %). mp 263-264 oC. IR (KBr): 2930 m, 1612 s, 1508 s
48
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, 59.20; H, 2.97; N, 10.55.
2-(2-Bromo-4-chloro-phenyl)-9-(4-chloro-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]-
naphthyridine (41k): Yield 0.455 g (83 %). mp 249-250 oC. 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, 59.77; H, 2.49; N, 10.51.
2-(2-Bromo-4-chloro-phenyl)-9-(4-Bromo-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]-
naphthyridine (41l): Yield 0.521 g (88 %). mp 269-270 oC. 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+] (48), 590 [M+2] (100), 592
49
[M+4] (74), 594 [M+6] (19). Anal. Calcd. for C27H15N4ClBr2 (590.67): C,55.10; H, 2.55;
N, 9.52. Found: C, 55.31; H, 2.81; N, 9.26.
9-(4-Chloro-phenyl)-7-phenyl-2-p-tolyl-7H-pyrazolo[3,4-h][1,6]naphthyridine (41m):
Yield 0.395 g (88 %). mp 243-244 oC. IR (KBr): 2919 m, 1612 s, 1512 s cm
-1.
1H 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, 75.05; H,
4.49; N, 12.74.
9-(4-Bromo-phenyl)-7-phenyl-2-p-tolyl-7H-pyrazolo[3,4-h][1,6]naphthyridine (41n):
Yield 0.420 g (85 %). mp 254-255 oC. IR (KBr): 2919m, 1596s, 1510s cm
-1.
1H 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). 13
C 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, 68.84; H, 3.50; N, 11.25.
9-(4-Chloro-phenyl)-2-(,4-nitro-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyrid-
ne (41o): Yield 0.427 g (89 %). mp 250-251 oC. IR (KBr): 2919 s, 1596 s, 1514 s cm
-1.
1H 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
50
(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 = 8.7Hz, 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 C27H16ClN5O2 (477.99): C, 67.92; H, 3.35; N,
14.67. Found: C, 67.69; H, 3.07; N, 14.90.
9-(4-Bromo-phenyl)-2-(4-nitro-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyridne
(41p): Yield 0.460 g (88 %). mp 274-275 oC. IR (KBr): 2919 m, 1596 s, 1551 m, 1511 s,
1357 m cm-1
. 1H 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, 62.44; H, 3.24; N, 13.20.
9-(4-Chloro-phenyl)-2-(3,4-di-CF3-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthyr-
idne (41q): Yield 0.495 g (87 %). mp 236-237 oC. 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,
61.51; H, 2.39; N, 9.48.
9-(4-Bromo-phenyl)-2-(3,4-di-CF3-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthy-
ridine (41r:. Yield 0.540 g (88 %). mp 248-249 oC. IR (KBr): 2930 m, 1595 s, 1505 s cm
-
51
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,
57.13; H, 2.19; N, 9.43.
9-(4-Chloro-phenyl)-2-(4-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthy-
ridine (41s): Yield 0.410 g (88 %). mp 239-240 oC. IR (KBr): 3022 m, 2919 s, 1596 s,
1501 s, 1070 m cm-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). 13
C 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, 72.45; H, 4.36; N, 12.40.
9-(4-Bromo-phenyl)-2-(4-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naphthy-
ridine (41t): Yield 0.425 g (83 %). mp 271-272 oC. IR (KBr): 3022 m, 2919 m, 1610 s,
1501 s, 1070 m cm-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
52
(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, 66.18; H, 4.07; N, 11.31.
9-(4-Chloro-phenyl)-2-(3,4-di-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]nap-
hthyridine (41u): Yield 0.424 g (86 %). mp 242-243 oC. IR (KBr): 3017 m, 2930 m,
1595 s, 1509 s, 1078 m cm-1
. 1H 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, 70.46; H, 4.53; N, 11.57.
9-(4-Bromo-phenyl)-2-(3,4-di-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naph-
thyridine (41v): Yield 0.469 g (87 %). mp 277-278 oC. IR (KBr): 3017 m, 2930 m, 1598
s, 1509 s, 1078 m cm-1
. 1H 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, 64.67; H, 4.18; N, 10.70.
53
9-(4-Chloro-phenyl)-2-(2,5-di-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]nap-
hthyridine (41w): Yield 0.430 g (87 %). mp 243-244 oC. IR (KBr): 3004 m, 2941 m,
1602 s, 1501 s, 1078 m cm-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, 70.95; H, 4.44; N, 11.12.
9-(4-Bromo-phenyl)-2-(2,5-di-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]naph-
thyridine (41x): Yield 0.476 g (88 %). mp 275-276 oC. IR (KBr): 3004m, 2941m, 1602s,
1501s, 1078m cm-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 (%): 536 [M+] (97), 538 [M+2] (90). Anal. Calcd. for C29H21N4O2Br (537.32): C,
64.92; H, 3.91; N, 10.44. Found: C, 64.70; H, 4.14; N, 10.69.
9-(4-Chloro-phenyl)-2-(2,4,6-tri-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]na-
phthyridine (41y): Yield 0.464 g (88 %). mp 247-248 oC. IR (KBr): 3004 m, 2941 m,
1602 s, 1501 s, 1075 m cm-1
. 1H 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),
54
8.53 (d, 2H, J = 8.6 Hz, Ar-H) 9.06 (s, 1H, Ar-H). 13
C 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, 69.23; H, 4.66; N, 10.48.
9-(4-Bromo-phenyl)-2-(2,4,6-tri-methoxy-phenyl)-7-phenyl-7H-pyrazolo[3,4-h][1,6]na-
phthyridine (41z): Yield 0.495 g (87 %). mp 281-282 oC. IR (KBr): 3004 m, 2941 m,
1602 s, 1501 s, 1075 m cm-1
. 1H 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, 63.86; H, 4.27; N, 9.64.
55
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