CHAPTER-Ishodhganga.inflibnet.ac.in/bitstream/10603/2211/10/10_chapter 1.pdf · drugs in the market are heterocyclic compounds, and about 90% of the drug research is focusing on heterocyclic

1

BIOLOGICAL ACTIVITY AND MICROWAVE ASSISTED SYNTHESIS OF HETEROCYCLIC COMPOUNDS - A BRIEF REVIEW

1.1 Introduction

Heterocyclic compounds play a vital role in biological systems. Many

natural products like vitamins, antibiotics, amino acids, plants pigments,

nucleic acids, drugs contain heterocyclic moiety. Heterocyclic compounds

play a critical role in the drugs and pharmaceutical industries. The

establishment of an efficient method of synthesizing heterocycles is

required for the development of pharmaceuticals and agrochemicals

since many bioactive compounds have a heterocyclic moieties. 80% of the

drugs in the market are heterocyclic compounds, and about 90% of the

drug research is focusing on heterocyclic compounds.

In the present study some novel heterocycles such as 2-

Aminopyrimidines, 1-Thiocarbomoylpyrazolines, Furano aurones, Furano

flavanones, 4-Chlorochromenes, Triazoles, Benzodifurans and

Furanostyryl compounds are synthesized under microwave irradiation

and screened for their antibacterial activity. Therefore it is worthwhile to

discuss a brief review on biological activity of Benzofurans, 2-

Aminopyrimidines, 1-Thiocarbamoylpyrazolines, Aurones, Flavanones, 4-

CHAPTER-I

2

Chlorochromenes, 1, 2, 3-Triazoles, Benzodifurans, Chalcones and

Furanostyryl compounds.

1.2 BIOLOGICAL ACTIVITY – A BRIEF REVIEW

Table-1.1: Biological activity of Benzofurans

Compound Structure Biological activity

Ref

Tremetone

O

O

CH3

1.1

Toxic to gold fish

1,2

Hydroxytremetone

O

O

CH3

HO 1.2

Toxic to gold fish

1,2

Dehydrotremetone

O

O

CH3

1.3

Bacteriostatic activity

1,2

Euparin

O

O

CH3

HO 1.4

Antitumor activity

1,2

Toxol O

O

CH3 OH

1.5

Antitumor, Bacteriostatic activity

1,2

Toxyl angelate

O

O

CH3 O CO

CC

CH3

H

H3C

1.6

Antitumor activity

1,2

3

Benzobromarone

O CH3

O

Br

OH

Br 1.7

Uricosuric agent

3

Amidarone

OH3CO O

O

H3CO 1.8

Antianginal activty

3

Benzarone

O CH3

O OH 1.9

Antihaemorrhagic agent activity

3,4

Benziodazone

O CH3

O OH

I

I 1.10

Coronary Vasodilator

3,4

Amidazone

O

O O

I

I

N

CH3

1.11

Antiarrhythmic activity

3,4

4

5-Amidino-2-(5-amidino-2-benzfuranyl)indole

O H

NHN NH

H2N NH

1.12

Recorniviral effect

5

5-Methyl-3-p-toluoyl-2[4-(3-diethylamino propoxy) phenyl] benzofuran

O

O

O N

1.13

β-Amyloid aggregation inhibitor

6

5

Table-1.2: Biological activity of 2-Aminopyrimidines

Methotrexate

N

N

NN

NH2

N

NHOHHO

H2N

O

OO

1.14

Antitumor activity

7

Aronoxil

CH3

CH3

NH N

N

Cl

NHOH

O 1.15

Antiatherosclerotic activity

8

Thonzylamine N N

NN

CH3

CH3

H3CO

1.16

Antihistamanic activity

8

Buspirone N

NNNN

O

O

1.17

Antianxiolytic activity

8

Enazadrem NH

N

N

CH3

HO

H3C

1.18

Antipsoriatic activity

8

6

Imatinib

HN

CH3

HN

N

N

O

N

NCH3

1.19

Anticancer activity

8

Table-1.3: Biological activity of 1- Thiocarbamoyl pyrazolines

1-Thiocarbamoyl-3-(2-furyl)-5-phenyl-2-pyrazoline

O

N N

H2N

S

1.20

Antidepressant activity

9

1-Thiocarbamoyl-3,5-di(2-furyl)-2-pyrazoline

O

N N

NH

S

O

1.21

Antidepressant activity

9

5-(4-Chlorophenyl)-4,5-dihydro-3-(4-hydroxy-3-methoxyphenyl)pyrazole-1-carbothioamide

N N

H2N

SHO

H3COCl

1.22

Antimycobacterial activity

9

7

5-(2-Chlorophenyl)-4,5-dihydro-3-(4-hydroxy-3-methoxy phenyl)pyrazole-1-carbothioamide

N N

H2N

SHO

H3COCl

1.23


9

Table-1.4: Biological activity of Aurones

(Z)-6-Methoxy-2-[phenyl methylene]-3-(2H)-benzofuranone

O

O

HOOH

H3CO

1.24

Leishmanicidal activity

10

(Z)-6-Hydroxy-2-[phenyl methylene]-3-(2H)-benzofuranone

O

O

HO

1.25

Leishmanicidal activity

10

(Z)-2-(3,4-Dihydroxy benzylidene)benzofuran-3(2H)-one

O

O

HOOH

1.26

Antioxidant activity

11

(E)-3’-O-β-D-Gluco pyranosyl-4, 5,6, 4’ -tetrahydroxy-7,2’-dimethoxy aurone

O

O

OCH3HO

HOOH

OCH3O O

HHO

OH

OH

H

OHOH

1.27

Antimicrobial activity

12

8

Table-1.5: Biological activity of Flavanones

Isoskuranetin

O

OCH3

O

HO

OH

1.28


13

(2S)-2’ –Methoxy kurarinone

OCH3

HO O

O

OH

5.12

H3CO

1.29

Antimalarial activity

14

Sophoraflavanone G

OH

HO O

O

OHHO

1.30


14

Lechianone A

OH

HO O

O

OHH3CO

1.31


14

9

Anastatin-A

O

O

O

O

HO

HOOH

1.32

Hepatoprotective activity

15

Anastatin-B

O

O

OH

OH

O

HO OH

1.33

Hepatoprotective activity

15

10

Table-1.6: Biological activity of Chromenes

7,7-Dimethyl-2-phenyl-7H-furo [3,2-f] chromene

O

O

1.34


16

2,7,7-Trimethyl-7H-furo[3,2-f] chromene

O

O

1.35


16

3,3-Dimethyl-8,9,10,11-tetra hydro-3H-benzo furo[3,2-f] chromene(6.4)

O

O

1.36


16

3-(7,7-Dimethyl-7H-furo[3,2-f] chromene-1-yl) propylacetate

O

O

H3COCO

1.37


16

11

Table-1.7: Biological activity of 1, 2, 3-Triazoles

(1-Benzyl-1H-1,2,3 -triazol-4-yl)methanol

NNN

HO

1.38


17

2-(1-(2-Methyl butyl)-1H-1,2,3-triazol-4-yl)propan-2-ol

NNN

HO

1.39


17

(1-(2-Methylbutyl)-1H-1,2,3-triazol-4-yl)methanol

NNN

HO

1.40


17

3-(4,5-Dihydro-1-phenyl-1H-1,2,3-triazol-4-yl)-6,7-dimethoxyquinolin-2(1H)-one

N

NN

N

O

H3CO

H3COH

1.41

Fluoroscent probes

18

12

Table-1.8: Biological activity of Benzodifurans

(R)-(1)-1-(8-Trifluoromethyl benzo[1,2-b;4,5,61] difuran-4-yl)-2-amino propene Hydrochloride

O

O

H3CNH2 . HCl

F3C 1.42

5-HT2A/2C receptor agonists

19

R)-(1)-1-(Benzo[1,2-b;4,5,61] difuran-4-yl)-2-aminopropene Hydrochloride

O

O

H3CNH2 . HCl

H 1.43


19

(R)-(1)-1-(8-Bromo benzo[1,2-b;4,5,61] difuran-4-yl)-2-amino propene Hydrochloride

O

O

H3CNH2 . HCl

Br 1.44


19

13

Table-1.9: Biological activity of Chalcones

(E)-3-(2,4-Dichlorophenyl)-1-(pyridin-2-yl)prop-2-en-1-one

NO

Cl Cl

1.45

Antibacterial activity

20

(E)-1-(4-chlorophenyl)-3-(2,6-dihydroxy phenyl) prop-2-en-1-one

O

HO

OH

H3C

1.46


21

(E)-3-(2,6-Dihydroxy phenyl)-1-p-tolyl prop-2-en-1-one

O

HO

OH

H3C

1.47


21

14

Table-1.10: Biological activity of Styryl compounds

4-((E)-2-(6-Methoxy benzofuran-2-yl)vinyl) -N,N-di methylbenzenamine

OH3CO N(CH3)2 1.48

A β- fibril inhibitors

2 2

222

4-((E)-2-(5-Methoxy benzofuran-2-yl) vinyl)-N,N-di methylbenzenamine

O N(CH3)2

H3CO

1.49

A β - fibril inhibitors

22

6-Desmethoxy hormothamnione

OOCH3

H3CO

OH

OH

OH

O 1.50

Cytotoxicity to 9 KB cell lines

23 24

Hormothamnione

OOCH3

H3CO

H3COOH

OH

OH

O 1.51

Cytotoxicity to 9 KB cell lines

23 24

15

1.3 MICROWAVE ASSISTED SYNTHESIS OF HETEROCYCLIC

COMPOUNDS - A BRIEF REVIEW

Synthesis of heterocycles is one of the most widely used areas in the

microwave chemistry, due to the high temperatures commonly employed

in heterocyclic condensation reactions. Furthermore, heterocycles are

among the most frequently encountered scaffolds in drugs and

pharmaceutically relevant substances. In 1986, Gedye and Giguere

reported for the first time that organic reactions could be conducted very

rapidly under microwave irradiation. Microwave–induced organic reaction

enhancement (MORE) chemistry has gained popularity as an un-

conventional technique for rapid organic synthesis25-48. Traditionally

organic synthesis is carried out by conductive heating with an external

heat source (Bunsen burner, Hot plate mantle, Water bath, Oil bath).

This is comparatively slow and inefficient method for transferring energy

into the system. Since it depends on the thermal conductivity of the

various materials that must be penetrated and results in the

temperature of the vessel being higher than that of the reaction mixture.

Whereas microwave irradiation produces efficient internal heating by

direct coupling of microwave energy with molecules (solvent, reagents,

catalysts) that are present in the reaction mixture. Microwave irradiation

is electromagnetic irradiation in the frequency range 0.3 to 300 GHz. The

microwave region of the electromagnetic spectrum is between infrared

16

radiation and radio frequencies. It corresponds to wavelengths of 1 mm

to 1m. Domestic and industrial microwave systems operate at 12.2 cm

(2.45 G Hz) or 33.3 cm (900 MHz).

Molecules with a permanent dipole that are subjected to the high

frequency oscillating electromagnetic field associated with microwaves

will try to align themselves with this field, these molecules are

continuously aligning and realigning with this field. The rapid motion

and resulting intermolecular friction cause intense internal heat that can

increase up to 10ºC per second. Due to this rapid temperature increment

the heating profile is different from conventional heating and it is

considered to be the main reason for accelerated reaction rates under

microwaves. A second type of the influence is specific microwave effect.

This can be expected when the polarity is increased during the reaction

from the ground state towards the transition state. When stabilization by

dipole-dipole electrostatic interactions of the transition state is more

effective than that of the ground state, this results in an enhancement of

reactivity by a reduction in the value of activation energy.

In the microwave environment chemical reactions usually proceed faster,

in higher yields and with less by products. Microwave technologies have

found especially extensive application in medicinal chemistry in the field

of drug discovery, where speed and automization, environment friendly is

matter of high importance.

17

1.3.1 Microwave reactors in Organic Synthesis:

There are two types of reactors used for microwave assisted synthesis.

1.3.1.1 Multimode reactors:

In the multimode version, the walls of the relatively large reactor space

reflect the irradiation, spreading it throughout the entire microwave

cavity. Domestic microwave ovens as multimode reactors are the most

common instruments used in organic synthesis. Since they are

comparatively inexpensive and readily available, using domestic

microwave cavity has done a lot of satisfying organic synthesis. In

household microwave ovens only time and the power irradiation during

this time can be varied as reaction parameters. Thus, the temperature is

undetermined and increases steadily during irradiation. A possible but

insufficient method to control the temperature or pressure is the on and

off switching of the microwave field within a given time interval. In

modern laboratory microwave systems, however, computer controls,

which allow setting of the attainable temperature or pressure as limiting

parameters, are state of the art. This feature is important with regard to

safety aspects of handling chemicals and is also crucial for both

reproducibility and the scale-up of reactions.

1.3.1.2 Monomode reactors:

In the monomode microwave instruments the irradiation is focused as a

standing wave directly on the reaction mixture. These instruments are

18

dedicated to small scale (0.2 ml to 5 ml). These dedicated instruments

contained many of the features required for controlled and reproducible

microwave assisted organic synthesis (MAOS) which included

homogeneous microwave field, magnetic stirring, pressure sensors, for

closed vessel reactions to avoid excessive pressure build-up and the

temperature sensors to control the rate and power of microwave

irradiation which in turn provided for temperature control. Continuous

flow reactors are nowadays available for both mono and multimode

cavities that allow the preparation of kilograms of materials by using

microwave technology. The key difference between the two types of

reactor systems is that whereas in multimode cavities several vessels can

be irradiated simultaneously in multi-vessel rotors (parallel synthesis) in

monomode synthesis only one vessel can be irradiated at the time.

1.4 PAST WORK

1.4.1 M. A. P. Martins et. al., 49 have reported the synthesis of

Isoxazolines (1.54) both by conventional heating and microwave

irradiation methods. The advantages obtained by the use of microwave

irradiation in relation to conventional heating method were

demonstrated.

Scheme-1.1: Synthesis of Isoxazolines (1.54)

19

Cl3CCOC CR2

OR1R3

+ NH2OH . HClPhMe, Py, 800C

MWI, 45W, 6 min

NO

R2R3

Cl3CHO

1.52 1.53 1.54or, 8-16 hr

R1 R2 R3 Yield (%) Conventional

heating MWI

Me Me H 82 95 Me Et H 86 90 Me n-Pr H 86 90 Me i-Pr H 81 95

1.4.2 B. Baruah et. al., 50 have reported the synthesis of isoxazolidines

(1.57) both by conventional heating and microwave irradiation methods.

The yields obtained in microwave irradiation and conventional heating

methods were discussed.

Scheme-1.2: Synthesis of isoxazolidines (1.57)

ONPhCH CHCH N Ph

O

+ H2C CHR

MWI6-30 min

PhPhCH=HC

R1.55 1.56 1.5710 hr-4 daysor

R Yield (%) Conventional

heating MWI

Ph 80 90 CO2Me 61 80

CN 66 80 p-MeC6H4 70 78

ClCH2 65 76

1.4.3 P. M. Fresneda et. al., 51 have reported the synthesis of Imidazoles

(1.60) both by conventional heating and microwave irradiation methods.

20

The advantages obtained by the use of microwave irradiation in relation

to conventional heating method were demonstrated.

Scheme-1.3: Synthesis of Imidazoles (1.60)

N

O N3

R1

R2CO2H, PMe3

or R2COCl, PPh2Me N

O HN

R1

R2

O

NR1

NH

N R2

NH4OAc, DMF

MWI, 10-35 min

1.581.59 1.60

or ,12-16 hr

R1 R2 Yield (%) Conventional

heating MWI

Bn 3-indolyl 55 68 H Me 50 67 H PhCH2 68 71

1.4.4 S. Kasmi et. al., 52have reported the synthesis of Thiazolines (1.64)

both by conventional heating and microwave irradiation methods. Yields

obtained in microwave irradiation and conventional heating methods

were discussed.

Scheme-1.4: Synthesis of Thiazolines (1.64)

R1NHCNHPh

S

+ R2COCH2Cl

MWI orSolvent free

Al2O3N

S

R2 NR1

Ph

N

S

R2 NR1 . HCl

Ph

OH / H2ON

S

R2 NR1

Ph

1.61 1.62

1.631.64

1.64

MWI or

21


heating MWI

Me Ph 65 95 Me PhCH2 70 98 Me i-Pr 75 97 Me t-Bu 70 90

1.4.5 M. Kidwai et. al., 53 have reported the synthesis of 1,3,4-

Thiadiazoles (1.67) both by conventional heating and Microwave

irradiation method. The advantages obtained by the use of microwave

irradiation in relation to conventional heating method were

demonstrated.

Scheme-1.5: Synthesis of 1,3,4-Thiadiazoles (1.67)

RCO2H H2NCNHNH2

S

acidic Al2O3or

N

S

NNH2R+

1.65 1.66 1.67

, 5-7hr

MWI, 40 sec

R Yield (%) Conventional

heating MWI

Me 70 89 C7H15 69 83 C9H19 72 86

C11H23 80 93

1.4.6 M. Kidwai et. al. 54 have reported the synthesis of 1,4-Dihydro

pyridines (1.71) both by conventional heating and microwave irradiation

method. Yields obtained in microwave irradiation and conventional

heating methods were discussed.

22

Scheme-1.6: Synthesis of 1,4-Dihydropyridines (1.71)

ArCHO+ 2MeCOCH2CO2Et + NH4OAc

NH

CO2EtAr

HEtO2C

Me Me

MWI

1.68 1.69 1.70

1.71

or

Ar Time Yield (%)

Conventional

heating

hr

MWI Conventional

heating

MWI

Solid

support

min.

Neat

reaction

min.

Solid

support

Neat

reaction

Ph 12 3.0 2.5 50 85 90

2-Furyl 13 2.5 2.0 47 82 87

2-Indolyl 8 6.0 4.5 50 81 86

piperonyl 24 6.5 5.0 77 83 88

1.4.7 V. Sridhar 55 has reported the synthesis of Indoles (1.74) both by

conventional heating and Microwave irradiation method. The advantages

obtained by the use of microwave irradiation in relation to conventional

heating method were demonstrated.

Scheme-1.7: Synthesis of Indoles (1.74)

R1CH2COR2 NH

R2

R1MeCO2HMWI. 28s

+

1.72 1.73 1.74

NHNH2 .HClor, 3 hr


heating MWI

Ph Me 60 68 H Ph 55 65

23

1.4.8 J. F. Zhou et. al., 56 have reported the synthesis of Pyridine

derivatives (1.77) both by conventional heating and microwave

irradiation method. Yields obtained in microwave irradiation and

conventional heating methods were discussed.

Scheme-1.8: Synthesis of Pyridine derivatives (1.77)

CHAr

OCHAr

+ CH2(CN)2 NaOH(s), MeOH

MWI,5-10 min N

CN

OMeCHAr

Ar

1.75

1.76

1.77

or , 3 hr

Ar Yield (%) Conventional

heating MWI

Ph 80 92 4-ClC6H4 70 91

4-MeOC6H4 85 98

1.4.9 T. Besson et. al., 57 have reported the synthesis of 4-Alkoxy quin-

azoline-2-carbonitriles (1.79) both by conventional heating and

microwave irradiation method. The advantages obtained by the use of

microwave irradiation in relation to conventional heating method were

demonstrated.

24

Scheme-1.9: Synthesis of 4-Alkoxy quinazoline-2-carbonitriles (1.79)

CNS

N

SN

MeO

MeO

Cl

NaH (1.1 equiv)ROH

MeO

MeON

N CN

ORMWI

1.78 1.79

or

R Time Yield (%) Conventional heating (hr)

MWI (min)

Conventional heating

MWI

Et 40 120 77 80 Et 40 120 29 80

n-Pr 40 73 39 49

1.4.10 Dandia et. al., 58, 59 have reported the synthesis of Spiro [1,5-

benzothiazepin-2,3’[3’H]-indol]-2’(1’H)-ones (1.81) both by conventional

heating and microwave irradiation method. Yields obtained in microwave

irradiation and conventional heating methods were discussed.

Scheme-1.10: Synthesis of Spiro [1,5-benzothiazepin-2,3’[3’H]-indol]-

2’(1’H)-ones (1.81)

HNO

O R

X SH

NH2

S

NH

HNO

X

MWI

1.801.81

R

orHCl /

Ethylene glycol /

25

R X Time Yield (%) Conventional heating (hr)

MWI (min)

Conventional heating (hr)

MWI (min)

Me H 3 5 65 91 Allyl H 3 5 20 50 Me Cl 3 5 69 97

Allyl Cl 3 5 60 85 Me Br 3 5 65 92

Allyl Br 3 5 45 60

1.4.11 M. S. Khajavi et. al., 60 have reported the synthesis of

Benzimidazo quinazolines (1.83) both by conventional heating and



demonstrated.

Scheme-1.11: Synthesis of Benzimidazoquinazolines (1.83)

N

HN

H2NRC(OEt)3

N,N-dimethylacetamide

MWI N

NN

R

1.82 1.83

or

R Time Yield (%) Conventional heating (hr)

MWI (min)


MWI (min)

H 1.5 2 87 85 Me 3.5 6 84 89 Et 4 6 93 94

n-Pr 4 6 88 91

1.4.12 D. Heber et. al., 61 have reported the synthesis of 1,2-Dihydro-2-

imino-7-methyl-1,6(6H)-naphthyridin-5-ones(1.85) both by conventional

26

heating and microwave irradiation method. Yields obtained in microwave

irradiation and conventional heating methods were discussed.

Scheme-1.12: Synthesis of 1,2-Dihydro-2-imino-7-methyl-1,6(6H)-

naphthyridin-5-ones (1.85)

MeN

OCHO

NHR1Me

R2CH2CN MeN

O

NMe NH

R2

R1MWI

1.84 1.85

R1 R2 Time Yield (%) Conventional heating (hr)

MWI (min)


MWI (min)

PhCH2 CO2Me 48 3 74 77 PhCH2 CO2Et 48 3 29 80 PhCH2 CO2Pr-i 48 3 67 82 PhCH2 CO2NH2 13 6 59 75

1.4.13 Dandia et. al., 62 have reported the synthesis of Spiro [Indoline-

3,2’-[1,3]thiazinane]-2,4’-diones (1.88) both by conventional heating and



demonstrated.

Scheme-1.13: Synthesis of Spiro [Indoline-3,2’-[1,3]thiazinane]-2,4’-diones

(1.88)

NH

X O

O

NH2

R+HSCH2CH2CO2H

Abs, EtOH, MWI NH

NS

O

OR

X

1.881.87

1.86or

27

X R Time Yield (%) Conventional heating (hr)

MWI (min)


MWI (min)

5-Cl 2-CF3 15 14 68 72 5-Cl 3-CF3 14 13 61 76

5,7-Me2 3-CF3 13 12 74 84 5-NO2 4-F 16 18 55 68

1.4.14 Danks, T. N. 63 have reported the solvent free synthesis of

Pyrroles (1.90) under microwave irradiation method.

Scheme-1.14: Synthesis of Pyrroles (1.90)

O

O NR

RNH2

MW, 100-200 W, 0.5-2.0 min, solvent-free

1.89 1.90R=CH2C6H5 2-ClC6H4

1.4.15 Y. L. Khemelnitsky et. al., 64 have reported the synthesis of

Imidazoles (1.93) both by conventional heating and microwave

irradiation method. The reaction time has brought down from hours to

minutes by the use of microwave irradiation in relation to a conventional

heating method were demonstrated.

28

Scheme-1.15: Synthesis of Imidazoles (1.93)

R1 H

O+ R2

OR3

O

Al2O3

NH4OAcN

R2R3

R1

NH

MW, 130W, 10 min, solvent-free 1.931.921.91

R1 =C6H5, 4-ClC6H4, 2-thiophenyl R2=R3=C6H5

Microwave irradiation: 10 min. Conventional heating: 4 hr, AcOH reflux.

1.4.16 J. Quiroga et. al., 65 have reported the synthesis of Dihydropyrido

pyrimidinones (1.97) both by conventional heating and microwave

irradiation method. The reaction time has brought down from hours to

minutes by the use of microwave irradiation in relation to a conventional

heating method was described.

Scheme-1.16: Synthesis of Dihydropyrido pyrimidinones (1.97)

N

N

OR

XMe

NH2

Ph

OCN Ar H

O+ +

N

N NH

O Ar

XMe

CN

Ph

R

MW, 600W, 20min, solvent-free1.97

1.961.951.94

X=O, S; R=H, CH3, Ar=C6H5, 4-CH3OC6H4, 4-ClC6H4

Microwave: 15-20 min., 70-75%

Conventional: EtOH reflux, 40-48 hr, 21-25%

1.5 Aim of the work:

From the foregoing review it is evident that a number of natural and

synthetic heterocyclic compounds possess biological activity. The shorter

reaction times, eco-friendly approach and expanded reaction range

29

offered by microwave assisted organic synthesis are suited to the

increased demands in the Therefore the aim of the present work is

Microwave assisted synthesis of chalcones and their novel heterocyclic

compounds to evaluate their biological activity.

Thus chapter-I deals with a brief review of biological activity and

microwave assisted heterocyclic synthesis.

Chapter-II describes the synthesis of 5-(2’-Amino-6’-Arylpyrimidin-4’-yl)-

2-benzoyl-6-hydroxy-3-methyl-benzo[b] furans (1.98) and 3-(2-Benzoyl-

6-hydroxy-3-methyl benzo[b]furan-5-yl)-5-(aryl)-4,5-dihydro-1H-pyrazole

carbothioamides (1.99).

1.98

OO OH

N

N NH2

Ar

12

3

4 5

67

1'

2'3'

4'

5' 6'

O OH

N

O

Ar

N

H2NS

1.99

HAHB

HX

1'

2'

3' 4'

5'

7'6'

12

3

45

Chapter-III describes the synthesis of 6-Benzoyl-5-methyl-2-[(Z)-1-

arylmethylidene]-2,3-dihydrofuro[3’,2’:4,5]benzo[b]furan-3-ones(1.51),2-

Benzoyl-3-methyl-7-aryl-6,7-dihydro-furo[3,2-g]chromen-5-ones(1.10)

and(5-Chloro-3-methyl-7-aryl-7H-furo[3,2-g]chromen-2-yl)(phenyl)

methanones (1.102).

1.100

O O ArO

O

1

2

3456

7 8

1.101

OO

O

O1

2

34 5 6

7

89 O O O

Cl

Ar

1.102

1

2

3 4 56

789H

H

H

Ar

30

Chapter-IV describes the synthesis of (E)-1-{2-Benzo yl-6-[(1-benzyl-1H-

1, 2, 3-triazol-4yl)methoxy]-3-methylbenzo[b]furan-5-yl}-3-aryl-2-propen

-1-ones (1.103).

O O O

N NN

O

Ar

1.103

1

2

34

5

67

Chapter-V describes the synthesis of E-(1)-(6-Benzoyl-3,5-

dimethylfuro[3’,2’:4,5]benzo[b]furan-2-yl)-3-(aryl)-2-propen-1-ones(1.104)

and 1-{6-Benzoyl-3-[(E)-2-(aryl)-1-ethenyl]-5-methyl furo [3’,2’;4,5]benzo

[b]furan-2-yl}-1-ethanones (1.105).

1.104 1.105

1

2

345

6

7 8OO

Ar

OO O O

Ar

OO1

2

345

67 8

Structures of the compounds synthesized were established based on

analytical and spectral data such as IR, 1H-NMR, 13C-NMR and mass

spectral data.

Antibacterial activity of all the compounds synthesized in the present

investigation is presented in chapter-VI.

We have utilized Milestone multisynth series microwave system and

modified LG microwave oven (perforated on the top to accommodate

31

reflux condenser and a 10-cm pipe to avoid microwave leakage) for the

synthesis of above mentioned heterocyclic compounds.

Mono & Multimode System Mono Mode Configuration Fig. 1.1 Fig. 1.2

Multimode Configuration Modified LG Microwave Fig.1.3 oven Fig.1.4

Results: Microwave heating has emerged as a powerful technique to promote a

variety of chemical reactions.

1. Significantly reduced reaction times.

2. Enhanced conversion and environment friendly.

3. Simple procedure for isolation of products.

4. Compounds synthesized were exhibited good to moderate

antibacterial activity.

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CHAPTER-Ishodhganga.inflibnet.ac.in/bitstream/10603/2211/10/10_chapter 1.pdf · drugs in the market are heterocyclic compounds, and about 90% of the drug research is focusing on heterocyclic