MICROWAVE ASSISTED SYNTHESIS OF SOME NOVEL CHALCONES · MICROWAVE ASSISTED SYNTHESIS OF SOME NOVEL CHALCONES ... 8 Introduction 19 9 Methods for the synthesis of Chalcones 20 10 Present

MICROWAVE ASSISTED SYNTHESIS OF

SOME NOVEL CHALCONES

A project report submitted in partial fulfillment of requirement for the

degree of

Master of Science

in

ORGANIC CHEMISTRY

by

MUSAAB MOHAMED ALI ELSANOOSI

(100712503079)

Under the Supervision of

PROF. D. ASHOK

DEPARTMENT OF CHEMISTRY

OSMANIA UNIVERSITY

HYDERABAD-500 007

2014

I

Dedicated to

my beloved mother, father,

brothers and sisters

II

ACKNOWLEDGMENT

It gives me great pleasure and profound privilege to place on record

my deep sense gratitude and indebtedness to my supervisor Prof. D. Ashok

whose constructive comments, unflagging optimism and scholarly guidance

throughout the present work has driven me towards the success of this

endeavor. It is pleasure to thank Prof. K. Nageswar Rao, Dean, Faculty of

Science, Osmania University, Prof. V. Uma, Head, Department of

Chemistry, Osmania University. for providing facilities to carry out the work

in the department.

.

It is pleasure to thank Prof. L.N. Sharada, Chairman, Board of Studies

in Chemistry, Department of Chemistry. I acknowledge with pleasure the

encouragement shown by Prof. V. Prabhakar Reddy, Prof. Ch. Prasad Rao,

Prof. Ch. Krishna Reddy, Prof. P. Leelavathi, Dr. M. Vijjualatha and Mr. P.

Vijay Kumar. I thank for the support of Mr. S. Ravi, Mr. A. Ganesh, Mr.

Mohan Gandhi, Mr. A. Vikas,Mrs. R. Kavitha and Mr. G. Srinivas Research

Scholars, in my thesis, without their help this work have been an unfinished

job.

Deeply from my heart with love and faith, I would like to thank my

beloved father Mr. Mohamed Ali Elsanosi and my mother Mrs. Amna

Abdulkarim for their encouragement and prays throughout my life, and my

special tribute goes to my teachers who have taught me to rise this level,

special thanks also to all my graduate friends, My apologies to all those who

have helped me but are not acknowledged. May God bless them all for ever.

III

Re-Accredited by NAAC with ‘A’ Grade

CERTIFICATE

This is to certify that the project work entitled “Microwave Assisted

Synthesis of Some Novel Chalcones” is submitted by Mr. MUSAAB

MOHAMED ALI ELSANOOSI in partial fulfillment for the award of

degree of Master of Science in Organic Chemistry. This work has been

carried out under my guidance and supervision in the Department of

Chemistry, Osmania University, Hyderabad, is original and has not been

submitted for any degree or diploma to this University or any other

University.

Date: 25th

September, 2014 D. Ashok

Dr. D. ASHOK Ph.D.

Professor of Organic Chemistry

Department of Chemistry

Osmania University Campus

Hyderabad - 500 007. India

040- 27682337 (O)

09391024769 (M)

Email : [email protected]

mailto:Email%20:%[email protected]

mailto:[email protected]

IV

DECLARATION

The project work embodied in this thesis has been carried out in the

Department of Chemistry, Osmania University, Hyderabad, under the

supervision of PROF. D. ASHOK, Department of Chemistry, Osmania

University, Hyderabad. This work is original and has not been submitted for

any degree or diploma to this University or any other University.

Date: 25th

September, 2014 MUSAAB ELSANOOSI

V

List of Abbreviation

br broad

13C NMR Carbon Nuclear Magnetic Resonance

CC Column Chromatography

d doublet

dd doublet of doublet

)))) Ultra sound reaction

DMF Dimethylformamide

EtOH Ethanol

PEEK Poly ether-ether-ketone

MAOS Microwave assisted organic synthesis

1H NMR Hydrogen Nuclear Magnetic Resonance

IR Infrared

DMSO Dimethyl sulfoxide

m multiplet

MORE Microwave induced organic reaction enhancement

Conven. Conventional method

m/z mass to charge ratio

M. P Melting point

ppm parts per million

DMS Dimethyl sulfide

RT Room temperature

s singlet

t triplet

TLC Thin Layer Chromatography

UV Ultraviolet

VI

Table of Contents

No. Title Page

1 Abstract IX

CHAPTER 1

2 Biological activity of heterocyclic compounds

1

3 Microwave assisted organic synthesis (MAOS)-a brief review 7

4 Microwave irradiation method differs from Conventional

heating method

12

5 Advantages of microwave assisted reactions over the

conventional reactions

14

6 Examples for Microwave irradiation reactions 15

7 Objective of current research 18

CHAPTER 2

8 Introduction 19

9 Methods for the synthesis of Chalcones 20

10 Present work

23

CHAPTER 3

11 Experimental 33

12 Conclusion 47

13 References 48

14 Publication 52

VII

List of Tables

Table

No.

Title Page

1.1 Biological activity of Chalcone derivatives 3

1.2 Biological activity of Quinoline derivatives 4

1.3 Biological activity of Piperidine derivatives 5

1.4 Biological activity of Pyrrolidine derivatives 5

1.5 Biological activity of Morpholine derivatives 6

2.1 Physical data of (E)-1-(1-Substituted naphthalen-2-yl)-3-(2-

morpholinoquinolin-3-yl)prop-2-en-1-ones

26


piperidinoquinolin-3-yl)prop-2-en-1-ones

29


pyrrolidinoquinolin-3-yl)prop-2-en-1-ones

32

VIII

List of Schemes

Scheme

No.

Title Page

2.1 Synthesis of (E)-1-(4-Aminophenyl)-3-(2-

morpholinoquinolin-3-yl)prop-2-en-1-one

20

2.2 Synthesis of (E)-1-(4-Aminophenyl)-3-(7-methyl-2-

morpholinoquinolin-3-yl)prop-2-en-1-one

20

2.3 Synthesis of (E)-3-(3-Aryl-3-oxoprop-1-en-1-yl)quinolin-

2(1H)-ones

21

2.4 Synthesis of (E)-1-Aryl-3-(2-chloroquinolin-3-yl)prop-2-en-

1-ones

21


1-ones

22


1-ones

22

2.1 Synthesis of (E)-1-(1-Substituted naphthalen-2-yl)-3-(2-

morpholinoquinolin-3-yl)prop-2-en-1-ones

26


piperidinoquinolin-3-yl)prop-2-en-1-ones

29


pyrrolidinoquinolin-3-yl)prop-2-en-1-ones

32

IX

ABSTRACT

In the present study, we have investigated the microwave assisted

synthesis of several (E)-1-(1-Substituted naphthalen-2-yl)-3-(2-substituted

quinolin-3-yl)prop-2-en-1-ones by base catalyzed Claisen-Schmidt

condensation reaction of 2-Morpholinoquinoline-3-carbaldehyde/ 2-

Piperidinoquinoline-3-carbaldehyde/ 2-Pyrrolidinoquinoline-3-carbaldehyde

with 1-(1-Hydroxynaphthalen-2-yl) ethanone/ 1-(1-Methoxynaphthalen-2-

yl)ethanone. The structures of the newly synthesized compounds were

confirmed by elemental analysis, and spectral data such as IR, 1H &

13C

NMR and Mass.

1

BIOLOGICAL ACTIVITY OF HETEROCYCLIC COMPOUNDS AND

MICROWAVE ASSISTED ORGANIC SYNTHESIS (MAOS)

- A BRIEF REVIEW

1.1 Biological activity of heterocyclic compounds

Infectious diseases account for about half of the deaths in tropical countries.

Bacterial diseases are type of infectious diseases caused by pathogenic bacteria.

Bacterial infections are one of the prominent causes of health problems, physical

disabilities and mortalities around the world. These results when the harmful

bacteria get into a body area, multiply their and thrash the body’s defensive

mechanism. It is notable that majority of bacteria are non pathogenic and are not

harmful to human health. Some bacteria are even helpful and necessary for the

good health. Millions of bacteria normally live in the intestine, on the skin and the

genitalia. Medicinal plants are a rich source of antimicrobial agents and provide a

safer and cost effective way of treating bacterial infections. Some of the natural

antibacterial compounds generally possess quinolines as a core unit. Thus synthesis

of such heterocycles became main focus for synthetic chemists.

Heterocyclic moiety is a pivotal core of many biologically and

pharmacologically interesting compounds. Any synthetic approach for these

compounds depends upon the availability cost of the starting materials, selection of

ring closure steps and the tolerance of the functional groups present in the

molecule. A vast number of nitrogen containing heterocyclic building blocks have

applications in pharmaceuticals and agro-chemical research and drug discovery.

Heterocyclic compounds have a large number of applications in dyes and polymer

chemistry. Several analogues of heterocycles show different biological activity.

2

More than 50% of the drugs used in the modern medicine are based on either

synthetic or natural heterocyclic systems. The quinolines scaffold and it derivatives

represent a major class of heterocycles and are widely found in natural products,

drugs

and exhibit significant role in medicinal chemistry. Several quinoline

derivatives have been reported to exhibit biological activities such as

antibacterial1 antimalarial

2, antiallergenic

3, anti-inflammatory

4 and antitumor

5.

Among the quinolines, 2-chloro-3-formylquinolines find an important place in

synthetic organic chemistry, as these are key intermediates for further β-annelation

of a wide variety of ring systems and for the inter-conversions of many functional

groups6.

Morpholine derivatives present a wide range of biological activities, they can

be used as inhibitors and deactivators of liver alcohol dehydrogenase, antitumor,

antiviral or antimicrobial agents, anti-inflammatory or antifungal drugs7.

Piperidine derivatives were reported for the various pharmacological activities such

as antimicrobials8, anticonvulsants


10, antidepressant

(Paroxetine)11

and attention-deficit hyperactivity disorder (ADHD)

(Methylphenidate) agents.

Pyrrolidine derivatives are well known for their versatile pharmacological

activities such as antimicrobial12

, antitumor13

, anti-HIV14

, anticonvulsant15

.

Chalcones are a class of privileged structures that have a wide range of biological

properties such as antimicrobial


17 and anticancer

18 activities

etc. Sofalcone is a gastroprotective chalcone based drug promotes healing of gastric

ulcer and they inhibit many types of enzymes. Chalcones constitute an important

class of natural products belonging to the flavonoid families19

, which are also key

3

precursors in the synthesis of many biologically important heterocycles such as

benzothiazepines20

, pyrazolines21

, 1,4-diketones22

and flavones23

.

Table 1.1: Biological activity of Chalcone derivatives

Compound Structure Biological activity Ref

(E)-1-phenyl-3-(2-(piperidin-

1-yl)quinolin-3-yl)prop-2-en-

1-one

Antidepressant

activity

24

Licochalcone

Anticancer activity

25

Xanthohumol

Anticancer activity

26

4

Table 1.2: Biological activity of Quinoline derivatives


Cinchonine

Antimalarial activity

27

Norfloxacin

Antibacterial activity

28

Mefloquite


29

5

Table 1.3: Biological activity of Piperidine derivatives


Paroxetine

Antiprotozoal activity

30

Methylphenidate

Attention Deficit Hyperactivity

Disorder

31

Table 1.4: Biological activity of Pyrrolidine derivatives


Nicotine


32

Desoxy-D2PM

Antimalarial activity

33

6

Table 1.5: Biological activity of Morpholine derivatives


3-(Diphenylmethyl)Morpholine

Stimulant and

Anorectic effect

34

Gefitinib

Anticancer activity

35

7

1.2 Microwave assisted organic synthesis (MAOS)-a brief review

There are major advancements in the last few years in the methodology of

synthetic chemistry, but one element of the process has not much changed since its

inception i.e. the use of conductive heating to perform chemical transformations.

However, with the advent of microwave assisted synthesis, there is for the first

time, a technology that will dramatically, change the way chemical synthesis is

performed by offering a new energy source, powerful enough to complete reactions

in minutes instead of hours or even days.

A microwave is a form of electromagnetic energy, which falls at lower

end of the electromagnetic spectrum and is defined in a measurement of frequency

as 300 to 300,000 MHz. This includes the region that will affect molecular rotation,

though the preferred frequency of 2450 MHz, chosen by microwave

instrumentation manufacturers falls below any of the rotational transitions that will

occur in molecules, one of the four available frequencies for industrial, scientific or

medical applications, 2450 MHz is preferred because it has the right penetration

depth to interact with laboratory scale samples and has become the standard for

bench top systems.

Microwave energy consists of an electric field and a magnetic field

though only the electric field transfers energy to heat a substance. Any interaction

from magnetic field is insignificant. The energy in microwave photons (0.03

K.cal/mole) is very low relative to the typical energies of 80-120 K.cal/mole for

chemical bonds. Thus, microwaves will not directly affect molecular structure. In

8

the excitation of molecules, the effect of microwave absorption is purely increased

kinetic energy.

Traditionally, chemical synthesis has been achieved through conductive

heating with an external heat source, where the temperature is elevated and heat is

driven into the substance, passing first through the walls of the vessel in order to

reach the solvent and reactants. This is a slow and inefficient method for

transferring energy into the system because it depends on the thermal conductivity

of the various materials that must be penetrated. It also results in a higher external

temperature than the final internal temperature, which is problematic as the

required internal temperature can only be reached by sufficiently increasing the

surface temperature of the material over the desired temperature. Microwave

heating is a different process. The microwaves couple directly with the molecules

that are heating, leading to a rapid rise in temperature, because the process is not

dependent upon the thermal conductivity of the materials, the result is an

instantaneous heating of anything that will react to either dipole rotation or ionic

conductions, the two fundamental mechanisms for transferring energy from

microwave to the substance being heated.

One of the most important aspects of microwave energy is the rate at which

it heats. Microwave will transfer energy in 10-9

seconds with each cycle of

electromagnetic energy. The kinetic molecular relaxation from this energy is

approximately 10-5

seconds. The energy transfers faster than the molecules can

relax, resulting in a non-equilibrium condition and high instantaneous temperatures

that effect the kinetics of the system. This enhances the reaction rate as well as the

yields. Activated complexes do not normally exist long enough to have an

9

opportunity to absorb microwave energy although there are a number of stabilized

intermediates, resident stabilized intermediates and other intermediates that are

much longer lived. Many of these have lifetimes longer than 10-9

seconds, so the

opportunity exists for them to couple directly with the microwave and be further

enhanced. Most intermediates are highly polar species and many of them are even

ionic in character, making them excellent candidates for microwave energy

transfer.

Microwave enhanced chemical reactions can be faster by as much as 1,000

fold this is based on experimental data, from numerous works, that have been

performed over the last 15 years. Using the rate equation, calculations were

performed to determine the temperatures required to get these reaction

enhancements, for a 1000 fold rate increase, it was determined that a temperature

enhancement of approximately 55 oC would be needed. For a 100-fold rate increase

the temperature would reach 185 oC and require approximately a 35

oC increase

over the bulk temperature. For a 10-fold enhancement, a 15-20oC increase would

be required. Thus, these instantaneous temperatures are very consistent with the

temperatures that would be expected in these systems and can fully account for the

reaction rate and yield enhancement. These calculations were also performed over a

range of temperatures and as expected, the lines are essentially parallel predicting

the instantaneous versus bulk temperatures.

Microwave heating allows chemical reactions to be shifted from kinetic

control to thermodynamic control because of the energy available. This can change

the product for a particular transformation. This mechanism is a probable

explanation for some of the work that has been done concerning selected

10

stereoisomers, which were generated using microwave versus conventional

heating.. Microwave heating is extremely useful in slower reactions where high

activation energies are required to do various transformations. With the elevated

molecular energy generated by the transfer of microwave energy, reactions that

required many hours or even days to complete have been accomplished in min. It is

also possible to use non-polar solvents to actually reduce the bulk heating and

directly energize the molecule. The solvent acts as a heat sink to pull energy way.

Frequently used processing techniques employed in microwave-assisted

organic synthesis involve solvent less dry-media procedures where the reagents

are readsorbed onto either a more or less microwave transparent (silica, alumina or

clay)36

or strongly absorbing (graphite)37

inorganic support which can additionally

be doped with a catalyst or reagent. The solvent-free approach was very popular

particularly in the early days of microwave assisted organic synthesis (MAOS)

since it allowed the safe use of domestic household microwave ovens and standard

open-vessel technology. Although a large number of interesting transformations

with dry-media reactions have been published in the literature, technical

difficulties relating to non-uniform heating, mixing, and the precise determination

of the reaction temperature remain unsolved, in particular when scale-up issues

need to be addressed. In addition phase-transfer catalysis (PTC) has also been

widely employed as a processing technique in MAOS38

.

Alternatively, microwave-assisted synthesis can be carried out in standard

organic solvents either under open or sealed-vessel conditions. If solvents are

heated by microwave irradiation at atmospheric pressure in an open vessel, the

boiling point of the solvent (as in an oil-bath experiment) typically limits the

11

reaction temperature that can be achieved. In the absence of any specific or non-

thermal microwave effects (such as the superheating effect at atmospheric pressure

which has been reported to be up to 40 °C)39

the expected rate enhancements would

be comparatively small. To nonetheless achieve high reaction rates, high-boiling

microwave-absorbing solvents such as DMSO, N-methyl-2-pyrrolidone (NMP),

1,2-dichlorobenzene (DCB) or ethylene glycol have been frequently used in open-

vessel microwave synthesis40

. However, the use of these solvents presents serious

challenges during product isolation. The recent availability of modern microwave

reactors with on-line monitoring of both temperature and pressure has meant that

MAOS in sealed vessels - a technique pioneered by Strauss in the mid 1990s41

has

been celebrating a comeback in recent years. This is clearly evident from surveying

the recently published literature in the area of MAOS and it appears that the

combination of rapid dielectric heating by microwaves with sealed-vessel

technology (autoclaves) will most likely be the method of choice for performing

MAOS in the future.

12

1.3 Microwave irradiation method differs from Conventional

heating method

1.3.1 Conventional heating method

In all conventional heating reactions, heating proceeds from a surface,

usually the inside surface of the reaction vessel. Whether one uses a heating mantle,

oil bath, steam bath or oven an immersion heater, the mixture must be in physical

contact with a surface that is at a higher temperature than the rest of the mixture.

In conventional heating, energy is transferred from a surface, to the bulk

mixture and eventually to the reacting species. The energy can either make the

reaction thermodynamically allowed or it can increase the reaction kinetics.

In conventional heating, spontaneous mixing of the reaction mixture may

occur through convection or mechanical means (stirring) can be employed to

homogenously distribute the reactants and temperature throughout the reaction

vessel. Equilibrium temperature conditions can be established and maintained.

Although it is an obvious point, it should be noted here that in all

conventional heating of open reaction vessels, the highest temperature that can be

achieved is limited by the boiling point of the particular mixture. In order to reach

higher temperature in the open vessel, a higher-boiling solvent must be used.

In conclusion, compared to conventional heating, microwave heating

enhances the rate of certain reactions by 10 to 1000 times. This is due to its ability

to substantially increase the temperature of a reaction.

13

1.3.2 Microwave irradiation method

Microwave heating occurs somewhat differently from conventional heating.

First, the reaction vessel must be substantially transparent to the passage of

microwaves. The selection of vessel material is limited to fluoropolymers and only

a few other engineering plastics such as polypropylene or glass fiber filled poly

ether-ether-ketone (PEEK).

Heating of the reaction mixture does not proceed from the surface of the

vessel; the vessel wall is almost always at a lower temperature than the reaction

mixture. In fact the vessel wall can be an effective route for heat loss from the

reaction mixture.

Second, for microwave heating to occur, there must be some component of

the reaction mixture that absorbs the penetrating microwaves. Microwaves will

penetrate the reaction mixture, and if they are absorbed, the energy will be

converted into heat. Just as with conventional heating, mixing of the reaction

mixture may occur through mechanical means (stirring) can be employed to

homogeneously distribute the reactants and temperature throughout the reaction

vessel.

14

1.4 Advantages of microwave assisted reactions over the

conventional reactions

Microwave-assisted reactions are emerging as an important tool in chemical

synthesis, the main advantages are:

o Reduction in reaction temperatures

o Increases in reaction rates over 10-10,000 times.

o Increased yields of 10-30% on an average.

o Increased selectivity in the product.

o Minimum side reactions due to rapid quenching

o Reduced solvent usage creates less wastage

o Environmentally clean solvent free processes.

In the field of organic synthesis it is mainly applied to drastically reduce the

reaction times of many synthetic reactions like Diels-Alder, Claisen, Ene reactions

etc.

There has been considerable interest in the application of microwave heating

upon chemical reactions. After much debate there seem to be general agreement

that in most cases microwave heating can only give rise to different temperature

regimes, which can be used in a profitable way. For instance when the reaction

need to be rapid incase of the synthesis of radiopharmaceuticals or when high

temperature need to be reached for the preparation of some inorganic compounds41

.

In addition microwave heating is ideal for solvent-free reaction systems, so called

“dry reactions”. Temperature effects are also the origin of the fact that a power

input change can cause a different.

15

1.5 Examples for Microwave irradiation reactions

1.5.1 Synthesis of 1-phenylpiperidine (1.3)42

.

Conventional: 15%- 20%

Microwave: 80%- 90%

1.5.2 Synthesis of methyl 3-phenyl-4,5-dihydroisoxazole-5-carboxylate (1.6) 43

.


Microwave: 90%- 98%

16

1.5.3 Synthesis of (E)-(2-nitroprop-1-en-1-yl)benzene (1.9) 44

.


Microwave:84%- 92%

1.5.4 Synthesis of (2E,2'E)-3,3'-(1,4-phenylene)bis(1-(4-hydroxyphenyl)prop-2-en-

1-one) (1.12) 45

.


Microwave: 85%- 98%

17

1.5.5 Synthesis of 9-phenyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione

(1.15) 46

.


Microwave: 84%- 95%

18

1.6 Objective of current research

The project report entitled “Microwave Assisted Synthesis of Some Novel

Chalcones” has been divided into three chapters. The first chapter deliberates a

brief review on biological activity of chalcones, heterocyclic compounds and a

brief review on microwave assisted organic synthesis. The second chapter intrigues

introduction and synthesis of quinoline chalcones. The third chapter deals with the

experimental.

Therefore the aim of the present investigation is to synthesize some novel

quinoline chalcones. As a part of our ongoing program towards the microwave

irradiation approach47

to the experimental set ups of induced organic reactions, the

concept of microwave induced organic reaction enhancement (MORE) chemistry

has been utilized for rapid and efficient synthesis of some novel heterocyclic

Chalcones.

19

MICROWAVE ASSISTED SYNTHESIS OF

SOME NOVEL CHALCONES

2.1 Introduction

Several quinoline derivatives exhibit a wide variety of biological activities. It

was also observed from the literature that chalcones are associated with various

biological activities. This leads to the conclusion that the combined effect of both

quinoline and chalcone moieties play an important role in imparting various

biological activities to title compounds. The microwave irradiation methods have

gained popularity as a nonconventional technique for rapid organic synthesis. It

offers a clean, cheap and convenient method of heating which often results in

higher yields and shortens reaction times. These prompted us to take up the

conventional and microwave irradiation synthesis of (E)-1-(1-Substituted

naphthalen-2-yl)-3-(2- Substituted quinolin-3-yl)prop-2-en-1-ones (2.1-2.3)

under

conventional and microwave irradiation.

R= H, Me

20

2.2 Methods for the synthesis of Chalcones

1) H. Kishor Chikhalia et al.,48

have reported the synthesis of (E)-1-(4-

Aminophenyl)-3-(2-morpholinoquinolin-3-yl)prop-2-en-1-one (2.6) by the

condensation of 2-morpholinoquinoline-3-carbaldehyde (2.4) and 4-

aminoacetophenone (2.5) in the presence of KOH in methanol at room temperature.

Scheme-2.1: Synthesis of (E)-1-(4-Aminophenyl)-3-(2-morpholinoquinolin-3-

yl)prop-2-en-1-one (2.6)

2) K. J. Mayan Patel et al.,48

have been reported the synthesis of (E)-1-(4-

Aminophenyl)-3-(7-methyl-2-morpholinoquinolin-3-yl)prop-2-en-1-one (2.8) by

Claisen-Schmidt condensation of 7-methyl-2-morpholinoquinoline-3-carbaldehyde

(2.7) and 4-aminoacetophenone (2.5) in the presence of 20% NaOH in methanol at

room temperature.

Scheme-2.2: Synthesis of (E)-1-(4-Aminophenyl)-3-(7-methyl-2-

morpholinoquinolin-3-yl)prop-2-en-1-one (2.8)

21

3) D. Karthik Kumar and S. P. Rajendra49

have synthesized (E)-3-(3-Aryl-3-

oxoprop-1-en-1-yl)quinolin-2(1H)-ones (2.11) by the condensation of 2-oxo-1,2-

dihydroquinoline-3-carbaldehyde (2.9) and aryl methyl ketone (2.10) in methanolic

KOH at room temperature.

Scheme-2.3: Synthesis of (E)-3-(3-Aryl-3-oxoprop-1-en-1-yl)quinolin-2(1H)-ones

(2.11)

4) S. Abdel-Sattar Hamad Elgazwy50

have synthesized (E)-1-Aryl-3-(2-

chloroquinolin-3-yl)prop-2-en-1-ones (2.13) by Claisen-Schmidt condensation of

2-chloroquinoline-3-carbaldehyde (2.12) and aryl methyl ketones (2.10) in the

presence of piperidine.

Scheme-2.4: Synthesis of (E)-1Aryl-3-(2-chloroquinolin-3-yl)prop-2-en-1-ones

(2.13)

22

5) Vandana Tiwari et al.,51

describes the synthesis of (E)-1-Aryl-3-(2-

chloroquinolin-3-yl)prop-2-en-1-ones (2.13) by the condensation of 2-

chloroquinoline-3-carbaldehyde (2.12), aryl methyl ketones (2.10) in the presence

of K2CO3 under microwave irradiation.

Scheme-2.5: Synthesis of (E)-1-Aryl-3-(2-chloroquinolin-3-yl)prop-2-en-1-ones

(2.13)

6) Vandana Tiwari et al.,52

have reported the synthesis of of (E)-1-Aryl-3-(2-

chloroquinolin-3-yl)prop-2-en-1-ones (2.13) by condensation of 2-chloroquinoline-

3-carbaldehyde (2.12), aryl methyl ketones (2.10) in the pressence K2CO3 & neutral

alumina in dichloromethane in the presence of ultrasound irradiation.

Scheme-2.6: Synthesis of (E)-1-Aryl-3-(2-chloroquinolin-3-yl)prop-2-en-1-ones

(2.13)

23

2.3 Present work

2.3.1 Synthesis of (E)-1-(1-Substituted naphthalen-2-yl)-3-(2-

morpholinoquinolin-3-yl)prop-2-en-1-ones (2.22-2.23) involves five steps:

2.3.1.1 Synthesis of 2-Chloroquinoline-3-carbaldehyde (2.17)

2-Chloroquinoline-3-carbaldehyde (2.17) is synthesized by Vilsmeier-Haack

reaction of acetanilide (2.16).

2.3.1.2 Synthesis of 2-Morpholinoquinoline-3-carbaldehyde (2.18)

2-Morpholinoquinoline-3-carbaldehyde (2.18) is synthesized by the reaction of 2-

Chloroquinoline-3-carbaldehyde (2.17) with morpholine.

24

2.3.1.3 Synthesis of 1-(1-Hydroxynaphthalen-2-yl)ethanone (2.20)

1-Naphthol on acetylation followed by Fries migration afforded 1-(1-Hydroxy

naphthalen-2-yl)ethanone (2.20)

2.3.1.4 Synthesis of 1-(1-Methoxynaphthalen-2-yl)ethanone (2.21)

1-(1-Hydroxynaphthalen-1-yl)ethanone (2.20) on methylation with dimethyl

sulphate afforded 1-(1-Methoxynaphthalen-1-yl)ethanone (2.21)

25

2.3.1.5 Synthesis of (E)-1-(1-Substituted naphthalen-2-yl)-3-(2-

morpholinoquinolin-3-yl)prop-2-en-1-ones (2.22-2.23) under conventional and

microwave irradiation methods

26

Table 2.1: Physical data of (E)-1-(1-Substituted naphthalen-2-yl)-3-

(2-morpholinoquinolin-3-yl)prop-2-en-1-ones

S.No Compound M. P.

(oC)

Reaction time Yield (%)

Conven.

(hr)

MWI

(min) Conven. MWI

1

(E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-

morpholinoquinolin-3-yl)prop-2-en-1-

one (2.22)

133-136 5 3 70 88

2

(E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-

morpholinoquinolin-3-yl)prop-2-en-1-

one (2.23)

126-129 5 3.5 72 92

27


piperidinoquinolin-3-yl)prop-2-en-1-ones (2.25-2.26) involves five steps:


(Discussed earlier in 2.3.1.1)

2.3.2.2 Synthesis of 2-Piperidinoquinoline-3-carbaldehyde (2.24)

2-Piperidinoquinoline-3-carbaldehyde (2.24) is synthesized by the reaction of 2-

Chloroquinoline-3-carbaldehyde (2.17) with piperidine.





28


piperidinoquinolin-3-yl)prop-2-en-1-ones (2.25-2.26) under conventional and


29


(2-piperidinoquinolin-3-yl)prop-2-en-1-ones

S.No Compound M. P.

(oC)


Conven.

(hr)

MWI

(min) Conven. MWI

1

(E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-

(piperidin-1-yl)quinolin-3-yl)prop-2-en-1-

one (2.25)

137-140 5 3 75 80

2

(E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-

(piperidin-1-yl)quinolin-3-yl)prop-2-en-1-

one (2.26)

125-128 5 3.5 74 95

30


pyrrolidinoquinolin-3-yl)prop-2-en-1-ones (2.28-2.29) involves five steps:



2.3.3.2 Synthesis of 2-Pyrrolidinoquinoline-3-carbaldehyde (2.27)

2-Pyrrolidinoquinoline-3-carbaldehyde (2.27) is synthesized by the reaction of 2-

Chloroquinoline-3-carbaldehyde (2.17) with pyrrolidine.





31


pyrrolidinoquinolin-3-yl)prop-2-en-1-ones (2.28-2.29) under conventional and


32


(2-pyrrolidinoquinolin-3-yl)prop-2-en-1-ones

S.No Compound M. P.

(oC)


Conven.

(hr)

MWI

(min) Conven. MWI

1

(E)-1-(1-Hydroxynaphthalen-2-

yl)-3-(2-(pyrrolidin-1-

yl)quinolin-3-yl)prop-2-en-1-

one (2.28)

129-132 4.5 3.5 68 91

2

(E)-1-(1-Methoxynaphthalen-2-

yl)-3-(2-(pyrrolidin-1-

yl)quinolin-3-yl)prop-2-en-1-

one (2.29)

122-124 5 4 72 93

33

Experimental


morpholinoquinolin-3-yl)prop-2-en-1-ones (2.22-2.23)


A Vilsmeier-Haack adduct was obtained from Phosphorus oxytrichloride (6.5

ml, 70 mmol) and N,N-dimethylformamide (2.3 ml, 30 mmol) at 0°C. N-

phenylacetamide (2.16) (1.35 g, 10 mmol) was added to the Vilsmeier-Haack

adduct and it was stirred at room temperature for overnight. Progress of the

reaction was monitored by TLC, after completion of the reaction, the reaction

mixture was poured in ice cold water and the white product was filtered and dried.

The compound was purified by recrystallization from petroleum ether : ethyl

acetate to yield 0.16 gm of pure 2-Chloroquinoline-3-carbaldehyde (2.17)

M. P. : 145-148 °C.

2.3.1.2 Synthesis of 2-Morpholinoquinoline-3-carbaldehyde (2.18)

A mixture of 2-Chloroquinoline-3-carbaldehyde (2.17) (0.19 gm, 1 mmol),

morpholine (0.10 gm, 1.2 mmol) and K2CO3 (0.55 gm, 4 mmol) in DMF (20 ml)

was heated to 80-90 °C. Progress of the reaction was monitored by TLC, after

completion of the reaction, the reaction mixture was poured in ice cold water. The

solid separated was filtered, washed with water, dried and purified by column

chromatography using silica-gel (hexane: ethyl acetate, 10 : 1, v/v) to yield 0.18 gm

of pure 2-Morpholinoquinoline-3-carbaldehyde (2.18)

M. P. : 158-160 °C.

34

1H NMR data of 2-Morpholinoquinoline-3-carbaldehyde:

1H NMR spectrum, δ, ppm: 3.48-3.51 (t, 4H, N-CH2), 3.92-3.94 (t, 4H, O-

CH2), 7.39-7.42 (t, 1H, ArH), 7.70-7.74 (t, 1H, ArH), 7.81-7.85 (t, 2H, ArH), 8.52

(s, 1H, C4-H), 10.19 (s, 1H, -CHO).


In 80ml hot glacial acetic acid, 50gm of zinc chloride was added and the

reaction mixture was refluxed till it is dissolved. Then 30 gm of 1-naphthol (2.19)

was added to reaction mixture and was refluxed for 8 hrs. The reaction mixture was

cooled and poured in ice cold water. The crude product was filtered, washed with

water and recrystallized from ethanol to obtain 17 gm of pure 1-(1-

Hydroxynaphthalen-2-yl)ethanone (2.20)

M. P. : 95-97 °C .

1H NMR data of 1-(1-Hydroxynaphthalen-2-yl)ethanone:

1H NMR spectrum, δ, ppm: 8.69 (s, 3H, COCH3), 7.24-7.27 (m, 1H, ArH),

7.50-7.56 (m, 1H, ArH), 7.60-7.64 (m, 2H, ArH), 7.74-7.76 (d, 1H, ArH), 8.44-

8.46 (d, 1H, ArH), 14.01 (s, 1H, Ar-OH).

35


1-(1-Hydroxynaphthalen-2-yl)ethanone (2.20) (0.18 gm, 1 mmol), K2CO3

(0.69 gm, 5 mmol) and dimethyl sulphate (0.14 gm, 1.1 mmol) was taken in 20 ml

of DMF and stirred for 4 hrs at room temperature. After completion of reaction, as

indicated by TLC, the reaction mixture was poured into ice cold water and

extracted with dichloromethane (2×20 ml), dried over Na2SO4 and the crude

product obtain 0.14 gm, was recrystallized from methanol.

M. P. : 108-109 °C.

1H NMR data of 1-(1-Methoxynaphthalen-2-yl)ethanone:

1H NMR spectrum, δ, ppm: 2.78 (s, 3H, COCH3), 4.01 (s, 3H, O-CH3), 7.56-

7.64 (m, 3H, ArH), 7.73-7.75 (d, 1H, ArH), 7.84-7.87 (m, 1H, ArH), 8.21-8.24 (m,

1H, ArH).

36

Synthesis of (E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-morpholinoquinolin-3-


a. Conventional method

A mixture of 2-Morpholinoquinoline-3-carbaldehyde (2.18) (0.24 gm, 1

mmol), 1-(1-Hydroxynaphthalen-2-yl)ethanone (2.20), (0.18 gm, 1 mmol) and

potassium hydroxide (0.12 gm, 3 mmol) was dissolved in ethanol (10 ml) and

stirred at room temperature. Progress of the reaction was monitored by TLC, after

completion of the reaction, the reaction mixture was poured in ice cold water and

neutralized with dil. HCl solution. The solid separated was filtered, washed with

water, dried and purified by column chromatography using silica-gel (hexane :

ethyl acetate, 10 : 1, v/v) to yield 0.29 gm of pure compound (2.22)

b. Microwave irradiation method


mmol), 1-(1-Hydroxynaphthalen-2-yl)ethanone (2.20) (0.18 gm, 1 mmol) and

potassium hydroxide (0.12 gm, 3 mmol) was dissolved in ethanol (5 ml), and

subjected to microwave irradiation at 180 W with 30 sec intervals. Progress of the


mixture was poured in ice cold water and neutralized with dil. HCl solution. The


chromatography using silica-gel (hexane : ethyl acetate, 10 : 1, v/v) to yield 0.36

gm of pure compound (2.22)

37

(E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-morpholinoquinolin-3-yl)prop-2-

en-1-one (2.22)

IR spectrum v, cm-1

: 1573 (C=C), 1625 (C=O). 1H NMR spectrum, δ, ppm:

3.43-3.45 (t, 4H, 2 X N-CH2-), 3.94-3.97 (t, 4H, 2 X O-CH2-), 7.33-7.35 (d, 1H,

ArH), 7.61-7.68 (m, 3H, ArH), 7.77-7.80 (m, 2H, ArH), 7.86-7.94 (m, 3H, ArH&

Hα), 8.17-8.21 (d, 1H, ArH& Hβ), 8.32 (s, 1H, ArH), 8.51-8.53 (d, 2H, ArH), 14.85

(s, 1H, ArOH). 13

C NMR spectrum, δc, ppm: 57.0, 66.9, 121.5, 123.7, 124.4, 124.5,

124.8, 124.9, 125.9, 126.0, 127.3, 127.4,126.7, 127.9, 130.0, 130.3, 130.6, 130.7,

142.1, 147.7, 164.6, 192.9 .Found, %: C, 76.25; H, 5.30; N, 6.30. C26H22N2O3.

Calculated, %: C, 76.82; H, 5.43; N, 6.48. M 411[M+H]+.

Synthesis of (E)-1-(1-Methoxynaphthalen-1-yl)-3-(2-morpholinoquinolin-3-




mmol), 1-(1-Methoxynaphthalen-2-yl)ethanone (2.21) (0.20 gm, 1 mmol) and







38











(E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-morpholinoquinolin-3-yl)prop-2-

en-1-one (2.23)

IR spectrum v, cm-1

: 1593 (C=C), 1645 (C=O). 1H NMR spectrum, δ, ppm: 3.38-

3.40 (t, 4H, 2 X N-CH2-), 3.81-3.83 (t, 4H, 2 X O-CH2-), 3.97 (s, 3H, -OCH3), 7.37-7.41

(m, 1H, ArH), 7.60-7.71 (m, 6H, ArH), 7.75-7.77 (d, 1H, ArH), 7.82-7.86 (m, 2H, ArH),

7.90-7.92 (m, 1H, ArH& Hα), 8.25-8.28 (m, 1H, ArH& Hβ), 8.30 (s, 1H, C4-H). 13

C NMR

spectrum, δc, ppm: 51.0, 64.0, 66.9, 122.6, 122.9, 124.4, 124.8, 125.0, 125.7,126.8, 127.6,

127.9, 128.1, 128.2, 130.6, 136.5, 137.0, 141.7, 147.7, 156.4, 159.6, 193.7. Found, %: C,

76.38; H, 5.69; N, 6.55. C27H24N2O3. Calculated, %: C, 76.34; H, 5.28; N, 6.52. M

425[M+H]+.

39


piperidinoquinolin-3-yl)prop-2-en-1-ones (2.25-2.26)



2.3.2.2 Synthesis of 2-Piperidinoquinoline-3-carbaldehyde (2.14)


piperidine (0.10 gm, 1.2 mmol) and K2CO3 (0.55 gm, 4 mmol) in DMF (20 ml) was

heated to 80-90 °C. Progress of the reaction was monitored by TLC, after




gm of pure 2-Piperidinoquinoline-3-carbaldehyde (2.24)

M. P. : 123-125 °C.

1H NMR data of 2-Piperidinoquinoline-3-carbaldehyde:

1H NMR spectrum, δ, ppm: 1.69-1.70 (m, 2H, -CH2), 1.78-1.79 (m, 4H, N-

CH2-CH2), 3.43-3.46 (t, 4H, N-CH2), 7.33-7.35 (t, 1H, ArH), 7.66-7.69 (t, 1H,

ArH), 7.76-7.83 (m, 2H, ArH), 8.47 (s, 1H, C4-H), 10.15 (s, 1H, -CHO).





40

Synthesis of (E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-piperidinooquinolin-3-



A mixture of 2-Piperidinoquinoline-3-carbaldehyde (2.24) (0.24 gm, 1



stirred at room temperaturer. Progress of the reaction was monitored by TLC, after















41

(E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-(piperidin-1-yl)quinolin-3-yl) prop-

2-en-1-one (2.25)

IR spectrum v, cm-1


1.66-1.69 (m, 2H, -CH2-), 1.75-1.81 (m, 4H, 2 X N-CH2-CH2-), 3.36-3.38 (t, 4H, 2

X N-CH2-), 7.19-7.21 (d, 1H, ArH), 7.31-7.35 (m, 1H, Ar-H), 7.41-7.45 (m, 1H,

ArH), 7.56-7.68 (m, 5H, ArH), 7.82-7.84 (d, 1H, C5-H), 7.92-7.94 (d, 1H, Hα),

8.08-8.13 (m, 2H, ArH& Hβ), 8.19 (s, 1H, C4-H), 14.98 (s, 1H, Ar-OH). 13

C NMR

spectrum, δc, ppm: 24.6, 26.0, 29.7, 42.3, 51.9, 113.4, 118.2, 120.8, 123.0, 123.8,

124.6,125.5, 125.9, 127.5, 127.8, 130.2, 130.5, 135.5, 137.3, 139.8, 145.3, 147.9,

160.7, 164.5, 193.1. Found, %: C, 79.36; H, 5.89; N, 6.85. C27H24N2O2. Calculated,

%: C, 79.39; H, 5.98; N, 6.22. M 409[M+H]+.

Synthesis of (E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-(piperidin-1-

yl)quinolin-3-yl)prop-2-en-1-one (2.26)

a. Conventional method:









42











(E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-(piperidin-1-yl)quinolin-3-yl) prop-

2-en-1-one (2.26)

IR spectrum v, cm-1

: 1590 (C=C), 1670(C=O). 1H NMR spectrum, δ, ppm:

1.55-1.69 (m, 6H, -CH2-), 3.30-3.39 (m, 4H, 2 X N-CH2-), 3.98 (s, 3H, -OCH3),

7.35-7.43 (m, 2H, ArH), 7.59-7.74 (m, 5H, ArH), 7.83-7.90 (m, 3H, ArH& Hα),

8.08-8.12 (m, 1H, ArH& Hβ), 8.19 (d, 1H, ArH), 8.27 (s, 1H, ArH). 13

C NMR

spectrum, δc, ppm: 24.3, 29.7, 52.0, 52.6, 118.7, 119.4, 122.8, 124.0, 124.3, 125.1,

125.9, 127.3, 127.8, 128.4, 128.6, 129.4, 129.8, 130.5, 136.8, 136.9, 137.6, 140.6,

147.9, 162.8, 194.5. Found, %: C, 79.76; H, 6.43; N, 6.40. C28H26N2O2. Calculated,

%: C, 79.29; H, 6.45; N, 6.34. M 423[M+H]+.

43


pyrrolidinoquinolin-3-yl)prop-2-en-1-ones (2.28-2.29)



2.3.3.2 Synthesis of 2-Pyrrolidinoquinoline-3-carbaldehyde (2.27)


pyrrolidine (0.10 gm, 1.2 mmol) and K2CO3 (0.55 gm, 4 mmol) in DMF (20 ml)

was heated to 80-90 °C. Progress of the reaction was monitored by TLC, after




gm of pure 2-Pyrrolidinoquinoline-3-carbaldehyde (2.27)

M. P. : 141-143 °C.





44

Synthesis of (E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-pyrrolidinoquinolin-3-



A mixture of 2-Pyrrolidinoquinoline-3-carbaldehyde (2.27) (0.22 gm, 1


















45

(E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-(pyrrolidin-1-yl)quinolin-3-yl)

prop-2-en-1-one (2.28)

IR spectrum v, cm-1


1.98-1.99 (t, 4H, N-CH2-CH2), 3.72-3.76 (t, 4H, N-CH2), 7.33-7.35 (m, 1H, ArH),

7.61-7.90 (m, 9H, ArH), 8.33-8.41 (m, 2H, C4-H& Hα), 8.50-8.52 (d, 1H, ArH&

Hβ), 14.89 (s, 1H, Ar-OH). 13

C NMR spectrum, δc, ppm: 29.6, 50.9, 122.5, 122.7,

123.3, 124.0, 125.0, 125.5, 126.5, 127.2, 127.8, 127.9, 128.6, 129.0, 129.3, 130.7,

133.9, 134.6, 136.8, 148.4, 156.8, 162.8, 194.2. Found, %: C, 79.10; H, 5.56; N,

7.05. C26H22N2O2. Calculated, %: C, 79.44; H, 5.52; N, 7.06. M 395[M+H]+.

Synthesis of (E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-(pyrrolidin-1-yl)

quinolin-3-yl) prop-2-en-1-one (2.29)


A mixture of 2-Pyrrolidioquinoline-3-carbaldehyde (2.27) (0.22 gm, 1








46



mmol), 1-(1-Methoxynaphthalen-2-yl) ethanone (2.21) (0.20 gm, 1 mmol) and








(E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-(pyrrolidin-1-yl)quinolin-3-yl)


IR spectrum v, cm-1


1.92-1.95 (m, 4H, N-CH2-CH2), 3.68-3.71 (t, 4H, N-CH2), 3.99 (s, 3H, O-CH3),

7.20-7.24 (m, 1H, ArH), 7.52-7.64 (m, 5H, ArH), 7.70-7.73 (m, 3H, ArH), 7.90-

7.91 (m, 1H, ArH& Hα), 8.04-8.08 (d, 1H, Hβ), 8.14 (s, 1H, C4-H), 8.26-8.29 (m,

1H, ArH). 13

C NMR spectrum, δc, ppm: 25.3, 50.7, 64.1, 121.8, 122.6, 123.0,

123.3, 124.2, 125.9, 126.0, 126.6, 126.7, 126.9, 127.8, 128.0, 128.1, 128.5, 130.5,

131.0, 136.6, 137.0, 143.4, 157.2, 192.5. Found, %: C, 79.40; H, 5.90; N, 6.84.

C27H24N2O2. Calculated, %: C, 79.33; H, 5.94; N, 6.22. M 409[M+H]+.

47

CONCLUSION

We have established an easy, high yielding convenient and green methods for

the synthesis of (E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-morpholinoquinolin-3-

yl)prop-2-en-1-one (2.22), (E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-

morpholinoquinolin-3-yl)prop-2-en-1-one (2.23), (E)-1-(1-Hydroxynaphthalen-2-

yl)-3-(2-(piperidin-1-yl)quinolin-3-yl)prop-2-en-1-one (2.25), (E)-1-(1-

Methoxynaphthalen-2-yl)-3-(2-(piperidin-1-yl)quinolin-3-yl)prop-2-en-1-one

(2.26), (E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-(pyrrolidin-1-yl)quinolin-3-yl)prop-

2-en-1-one (2.28), and (E)-1-(1-Methoxynaphthalen-2-yl)-3-(2-(pyrrolidin-1-

yl)quinolin-3-yl)prop-2-en-1-one (2.29)

48

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52

Publication

Microwave assisted synthesis of (E)-1-(Substituted naphthalenyl)-3-(2-substituted

quinolin-3-yl) prop-2-en-1-ones. (Communicated to Russian Journal of General

Chemistry).

-2-200224466881010121214141616

1.0 1.1 1.1

2.1

1.0

1.2

3.3

1H NMR spectrum of 1-(1-hydroxynaphthalen-2-yl)ethanone (2.20)

-2-200224466881010121214141616

1.0 1.0 1.0

3.1 3.2

3.1

1H NMR spectrum of 1-(1-methoxynaphthalen-2-yl)ethanone (2.21)

-2-200224466881010121214141616

1.0

2.4

1.3

1.1 1.2

4.6 4.6

1H NMR spectrum of 2-Morpholinoquinoline-3-carbaldehyde (2.18)

-2-200224466881010121214141616

1.0 1.1

2.1

1.1 1.0

6.9

3.3

1H NMR spectrum of 2-Piperidinoquinoline-3-carbaldehyde (2.24)

IR spectrum of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2-morpholinoquinolin-3-yl) prop-2-

en-1-one (2.22)

IR spectrum of (E)-3-(1-methoxynaphthalen-2-yl)-1-(2-morpholinoquinolin-3-yl)


IR spectrum of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2-piperidinooquinolin-3-yl) prop-

2-en-1-one (2.25)

IR spectrum of (E)-1-(1-methoxynaphthalen-2-yl)-3-(2-(piperidin-1-yl)quinolin-3-

yl) prop-2-en-1-one (2.26)

IR spectrum of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2-pyrrolidinoquinolin-3-yl)


-2-200224466881010121214141616

1H NMR spectrum of (E)-1-(1-methoxynaphthalen-2-yl)-1-(2-morpholinoquinolin-3-yl)prop-2-en-1-

one (2.23)

Aromatic Rrgion of (E)-1-(1-methoxynaphthalen-2-yl)-3-(2-morpholinoquinolin-3-yl)prop-2-

en-1-one (2.23)

-2-200224466881010121214141616

0.9 1.0 1.0 1.0

2.0

1.0

2.2

3.4

2.1

3.9 4.0

2.1

1H NMR spectrum of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2-piperidinoquinolin-3-yl)prop-2-en-1-one

(2.25)

-2-200224466881010121214141616

1H NMR spectrum of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2-pyrrolidinoquinolin-3-yl)prop-2-en-1-

one (2.28)

Aromatic Region of (E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-pyrrolidinoquinolin-3-yl)prop-2-

en-1-one (2.28)

00252550507575100100125125150150175175200200

13C NMR spectrum of (E)-1-(1-methoxynaphthalen-2-yl)-3-(2-morpholinoquinolin-3-yl)prop-2-en-

1-one (2.23)

00252550507575100100125125150150175175200200

13C NMR spectrum of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2-piperidinoquinolin-3-yl)prop-2-en-1-one

(2.25)

Aromatic Region of (E)-1-(1-Hydroxynaphthalen-2-yl)-3-(2-piperidinoquinolin-3-yl)prop-2-

en-1-one (2.25)

00252550507575100100125125150150175175200200

13C NMR spectrum of (E)-1-(1-methoxynaphthalen-2-yl)-3-(2-(pyrrolidin-1-yl)quinolin-3-yl)prop-2-en-

1-one (2.29)

Mass spectrum of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2-morpholinoquinolin-3-yl) prop-2-en-1-one (2.22)

Mass spectrum of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2-pyrrolidinoquinolin-3-yl) prop-2-en-1-one (2.28)

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