CHAPTER 1shodhganga.inflibnet.ac.in/.../10603/81957/9/09_chapter1.pdf · 2018. 7. 8. · 6 N N H N N Ar R N N H R O HO ArNHNH 2 24 25 2) P.Victory et al [37] synthesized pyrazolo[3,4-h][1,6]naphthyridine-5,9-diamines

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 elemental 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 corresponded

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 protons 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 molecules

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


= 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):


-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),



[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),



[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),



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):


-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


= 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


= 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


= 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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