7

CHAPTER II

LITERATURE REVIEW

2.1 PYRAZOLINE

Pyrazoline is a five membered heterocyclic compound containing two nitrogen

atoms in adjacent position and contains two endocyclic double bonds. Pyrazoline is

dihydropyrazoline possessing only one endocyclic double bond.

Depending on the position of the double bond three forms of pyrazoline are possible.

These are 1- pyrazoline, 2-pyrazoline and 1, 3- pyrazoline47

. Among all the

pyrazolines, 2-pyrazoline has gained attraction and is frequently studied one48

.

Pyrazolines are unique in their chemical behaviour not only among

heterocyclic compounds in general, but also among related azoles. This is because

8

pyrazoline possesses the typical properties of the aromatic system, which are in fact

rather pronounced in these derivatives, together with the high liability of the ring

under certain condition. Although pyrazoline derivatives have been known for more

than 80 years, the investigation of their chemistry commended rather slowly. Earlier

studies were mainly devoted to the development of synthetic methods. Recently the

attention was focused on the investigation of chemical properties and in particular on

the peculiarities of the behaviour of pyrazoline derivatives and the elucidation of their

physicochemical characteristics. This enabled new datas to be obtained that were

considerable importance. Pyrazoline derivatives have a long history of application in

agrochemicals as herbicides and insecticides and in pharmaceutical industry as

antipyretic and anti-inflammatory. Antipyrine is one of the earliest synthetic drug.

Now a days vast number of compounds with pyrazoline nucleus have been reported to

show a broad Spectrum of biological activity including antimicrobial, antifungal,

antioxidant, antiamoebic, analgesic, antitubercular, neuroprotective, anticancer,

antiproliferative, antiviral, anticonvulsant, muscle relaxant, anti-inflammatory

activities. Due to its wide range of biological activity, pyrazolines ring constitutes a

relavent synthetic route in pharmaceutical industry. In fact, such a heterocyclic moiety

represents the core structure for number of drugs.

2.2 SYNTHETIC REVIEW OF PYRAZOLINE DERIVATIVES

Some 1-(4-arylthiazol-2-yl)-3,5-diaryl-2-pyrazoline derivatives have been

synthesized by reacting 1-thiocarbamoyl-3,5-diaryl-2-pyrazoline derivatives with

phenacetylbromide in ethanol. The structural elucidation of the compounds were

performed by, IR, 1H-NMR and Mass Spectral data and elemental analysis

49.

9

Ten new fluorine-containing 1-thiocarbamoyl-3,5-diphenyl-2-pyrazolines have

been synthesized in 80 - 85% yields by a microwave- promoted solvent–free

condensation of 2,4-dichloro-5-fluoro chalcones with thiosemicarbazide over

potassium carbonate.

O

R1 R3

R2

H2N

NH

S

NH2

N

N

NH2

S

R1

R3

R2

CH3

F

Cl

Cl

O OHC

R

C

F

Cl

Cl

O

CH

CH

R

MW

F

Cl

Cl

N

N

HA HB

HX

R

C

NH2

H2N C NHNH2

S

Basic alumina/K2CO3 MW

S

10

The work–up is simple and involves treatment with ice cold water50

. A considerable

increase in the reaction rate has been observed, with better yields.

J.Safaei-Ghomi et al51

synthesized ten new N-phenylpyrazoline derivatives

by condensation of chalcones with phenylhydrazine in the presence of potassium

carbonate in reflux conditions. The work up is simple and involves treatment with ice-

cold water.

Several52

chalcones were synthesized by condensing 4-hydroxy-3-

methylacetophenone on condensation, with appropriate aldehyde in methanolic

potassium hydroxide solution yielded the corresponding chalcones. These

corresponding chalcones were reacted with phenyl hydrazine in glacial acetic acid

which led to the formation of novel 4-[5-(substituted phenyl)-1-phenyl-4,5–dihydro-

1H-3-pyrazolyl]-2-methylphenol derivatives

CH3

O

X'

+

X

OHC

O

XX'

K2CO

3PhNHNH

2

NN

X

X'

NaOH

EtOH

CH3

OH

CH3

O

R-CHO+KOH

CH3OH

R

O

OH

CH3

N

N

R

CH3

OH

PhNHNH2

CH3COOH

11

A.Aniskov et al53

have reported that the interaction of

α,β-unsaturated ketones of furan series with thiosemicarbazide under basic catalysis

leads to 3-furyl-2-thiocarbamoylpyrazolines since nitrous nucleophilic centre of a

reagent is activated where as the products of intermolecular cyclization of

thiosemicarbazones under conditions of acid activation of sulfureous necleophile are

spirocyclic furylmethylene 1,3,4-thiadiazolines.

The reation of α,β-chalcone ditosylates54

with various reagents such as

phenylhydrazine hydrochloride, semicarbazide hydrochloride and thiosemicarbazide

in suitable conditions leads to 1,2-aryl shift, thereby providing a novel route for the

synthesis of 1,4,5-trisubstituted pyrazoles

O

R2

R1

N

NH

NH2

S

O

R2

O

R1NEt3D

O

R2

R1

NN

-

NH2

S

H+

O

R2

R1

NN

NH2S

H2NNHCSNH2

Ar-

C CH CH Ar'

O OTS OTS

N

N

CONH2

Ar'

Ar-

N

N

CSNH2

Ar'

Ar-H

2NCSNHNH

2

EtOH D

EtOH D

H2NCONHNH

2.HCl

12

Sainath B. Zangade et al55

reported an efficient and facile reaction has been

shown between 2-hydroxychalcone with hydrazine hydrate in ethanol in presence of

catalytic amount of glacial acetic acid under irradiation of solar thermal energy to

afford 2-pyrazoline. Cyclised product established on the basis of IR, NMR, MS,

13C-NMR and elemental analysis.

Ar

O

Ar'

EtOH, AcOH, NH2NH2

Irradiation under sunlight

25-30 min. , 43 0C

N N

ArAr'

H

Manuel Nogueras et al56

reported a series of new 1,3-diaryl-5-(1-phenyl-3-

methyl-5-chloropyrazol-4-yl)-4,5-dihydropyrazole derivatives have been synthesized

under sonication conditions in ethanol or methanol/glacial acetic acid mixture (5/1

ratio) with two equivalents of hydrazines and seven kinds of chalcone-like

heteroanalogues obtained from 5-chloro-3-methyl-1-phenyl- 1H-pyrazole-4-

carbaldehyde. The structures were established on the basis of NMR, IR, MS and

element analysis. This method provides several advantages over current reaction

methodologies, including a simple work-up procedure, shorter reaction times (2 – 20

min) and good yields (65% – 80%).

N

N

N

N

Ar

Ar'

Cl

O

Ar

N

N

Cl

Ar'-NHNH2

C2H5OH/ACETIC ACID

))))

13

Sainath B. Zangade et al57

reported an efficient, green and facile reaction has

been reported between 2’ hydroxychalcones and hydrazine hydrate in

2 methoxyethanol in presence of catalytic amount of acetic acid under irradiation of

tungsten light to afford 2 pyrazolines. Present methodology presents several

advantages including simple reaction procedure, no need of catalyst/special apparatus

and short reaction time giving quantitative yields of product.

Ar

O

Ar'

Irradiation under tungtun lightN N

ArAr'

H

NH2NH2, 2-Methoxyethanol,

Acetic acid

B Shivarama Holla et al58

reported the condensation of a series of aromatic

ketones with aromatic aldehydes under aldol conditions affords 1-aryl-3-(substituted-

phenyl/phenyl furanyl/thienyl)-2-propen-1-ones . The resulting propenones undergo

facile and clean cyclization with hydrazine and substituted hydrazine derivatives to

yield 3-aryl-5-(substitutedphenyl/phenylfuranyl/thienyl)-2-pyrazolines .This reaction

is carried out in the presence of Amberlyst–15 catalyst to afford the above pyrazolines

in considerably good yield. All the synthesized compounds have been characterized

by spectral studies

Ar

O

Ar'

N N

ArAr'

R

R-NHNH2,Amberlyst-15

Toluene, Reflux

14

Mamaghani et al59

synthesized 1, 5-Diarylpyrazoles by the reaction between

Baylis-Hillman adducts and phenylhydrazine hydrochloride in 1,2-dichloroethane

under sonication with reaction times of 60 -180 minute. The reactions proceeded

region selectively to afford the desired products in 80 - 90% yields. The same reaction

carried out by simply heating the reaction mixture (80°C) produced the products in

lower yields (60 - 75%) and required longer reaction times (6-9 h).

Et

O

O

OH

Ar

NHNH2 .HCl

N

NAr

MeEt

ClCH2CH2Cl

60oC, 60-180 min)))) ,

Pathak et al60

conducted a comparative study between four activating

methods for obtaining N-acetyl-pyrazolines, including reflux, solvent-free conditions,

microwave irradiation and ultrasonic irradiation. Microwave irradiation was found to

be the most efficient activating method, followed by ultrasound. Employing

ultrasound, there actions of 1,4-penta-dien-3-ones with hydrazine and acetic acid in

ethanol went to completion in 10-25 minutes and afforded the products in good

yields.

15

O

R R

NH2NH2.H2O

CH3COOH

Ethanol

)))), 30oC, 10-25 min

NN

O

R

R

Pizzuti et al61

described a greener, ultrasound-assisted synthesis of 1-thio

carbamoyl-3,5-diaryl-4, 5-dihydropyrazoles from chalcones and thiosemicarbazide

catalyzed by KOH. The products were obtained in high purity and in good yields in

only 20 minutes via a simple filtration of the reaction mixture.

O

R

H2N

NH

S

NH2

NN

NH2

S

R

KOH, EtOH

)))), RT, 20min

16

Gupta et al62

utilized an ultrasonic cleaning-bath to promote the cyclisation reaction

between chalcones andphenylhydrazine under acid conditions, giving thedesired

cyclisation products in good yields.

O

NN

)))), 25-40oC,30-100min

NHNH2

RCl

RCl

AcOH

Nabid et al63

reported multi component ultrasound-assisted protocol for the

synthesis of bridgehead pyrazoled erivatives was developed by Nabid and co-workers

.Under ultrasonic irradiation, the reaction between phthalhydrazide, malononitrile or

ethylcyanoacetateand aromatic aldehydes in the presence of triethylamine

furnished1H-pyrazolo-[1,2-b]-phthalazine-5,10-diones in very good yields.

O

NH

NH

O

R CN

Ar H

O N

N

O

O

NH2

R

Ar

TEA, EtOH

)))), 50oC, 60min

17

Li et al64

reported3-Aryl-2,3-epoxy-1-phenyl-1-propanone reacted under

ultrasonic irradiation withphenylhydrazine catalyzed by HCl at room temperature to

produce 1,3,5-triarylpyrazoles in 69 - 99% yields. The same reactionsperformed in

the absence of sonication gave substantially poorer yields.

O

O

RNHNH2

NN

R

HCl, EtOH

)))), RT, 45-165 min

Ahmad et al65

synthesized 3,4-Dimethyl-2,4-dihydropyrazolo[4,3-

c][1,2]benzothiazine-5,5-dioxide by the cyclisation of 1-(4-hydroxy-2-methyl-1,1-

dioxido-2H-1,2-benzothiazin-3-yl)ethanone with hydrazine under ultrasonic

irradiationinonly 10 minutes. The product was used for the preparation of

acetohydrazidederivatives with potential antioxidant and antibacterial activities.

S

N-O

-O

OH

O

S

N

NHN

O O

NH2NH2.H2O))))

65oC, 10 min

18

Machado et al66

reported the preparation ofseveral ethyl 1-(2,4-

dichlorophenyl)-1H-pyrazole-3-carboxylates that are structurallyanalogous to the

CB1 receptor antagonists used in the treatment of obesity. Cyclisation of 4-alkoxy-2-

oxo-3-butenoic ester and 2,4-dicholorophenylhydrazine hydrochloride under

sonication (10 - 12 min) or conventional thermal conditions (2.5 - 3 h) region

selectively afforded the desired products. The use of ultrasound proved to be

fundamental for reducing the reaction time.

Kanagarajan et al67

acetylated bis-pyrazole derivatives was based on the

sonication of bis-chalcones and hydrazine in the presence of acetic anhydride during

10 - 20 minutes. The same reactions required 5 - 8 hours to go to completion when

carried out under heating in the absence of ultrasound and afforded lower yields (55-

70%) than those of Sonochemicalassisted reaction.

OO

R

R

N

N

N

N

NH2NH2.H2O/(CH3CO)2OCH3COONa

)))), 45oC, 10-20min

O

O

CO2Et

R1

R2 R3

ONHNH2.HClCl

Cl

N

N

EtO2C

Cl

Cl

R2

R1

)))), 68-72oC, 10-12 min

EtOH

19

Zou et al68

reported a four-component one-pot reaction of ethyl acetoacetate,

aromatic aldehydes, hydrazine, and malononitrile in water afforded dihydropyrano [2,

3-c] pyrazoles in good yields under ultrasonic irradiation (79-95%). Again,

acomparative study in the absence of ultrasound showed that the products were

obtained in lower yields (70-86%) and demanded longer reaction times (1-5 h).

OEt

O O

Ar H

O

NH2NH2.H2O CNNC

H2O

)))), 5OoC, 15-40 minHN

NH O NH2

CN

Ar

2.3 BIOLOGICAL REVIEW OF PYRAZOLINE DERIVATIVES

2.3.1 ANTIINFLAMMATORY ACTIVITY

Bekhit A A et al69

synthesized novel series of structurally related 1H-

pyrazolyl derivatives. All the newly synthesized compounds were tested for their in

vivo anti-inflammatory activity. The identity of the compounds was confirmed by

1H-NMR and IR spectral data. The elemental analysis was also performed.

N

N

NN

CH3

S

Br

Br

1

20

Barsoum FF et al70

reported the Facile synthesis of bis (4,5-dihydro-1H-

pyrazole-1-carboxamides) and evaluated for their anti-inflammatory properties. The

structural assignments of the new compounds were based on their elemental analysis

and spectral data .

2

Sushma Drabu et al71

have the synthesis, anti-inflammatory, ulcerogenic and

antibacterial activities of 1,3,5-trisubstituted pyrazolines

N N

N

O

R

R'

3

Anna Pratima Nikalje et al72

Synthesized 3, 5 – diaryl / heteryl substituted -

2-pyrazolines by reaction of substituted prop-2–ene-1-ones with hydrazine hydrate in

acetic acid. The newly synthesized compounds were evaluated and tested for their

anti- inflammatory activity using Carageenan-induced hind paw edema model in

NN

R

NH2O

21

albino rats. In this study indomethacin was used as standard drug. All the synthesized

pyrozoline derivatives except a few have shown significant activity.

R

N

NH

R1

4

Setaraman venkataraman et al73

reported that pyrazolines were prepared

from substituted acetophenones and substituted benzaldehydes and condensed with

hydrazine hydrate in ethanol. All the synthesized compounds were screened for their

antibacterial and anti-inflammatory activities. Test compounds were found to exhibit

potent anti-inflammatory activity.

N NH

R2R1

R3

5

Md.Afzal Azan et al74

reported that the derivative of 2-(1, 3-benzothiazol-2-yl

sulfanyl)-1-(3, 5-disubstituted-4, 5-dihydro-1H-pyrazole-1-yl) ethanones bearing 2-

pyrazoline at the 2nd

position. Compounds exhibited significant antimicrobial activity

against psedomonous aeruginosa and showed significant analgesic and anti-

inflammatory activity.

22

N

N

Ar1

Ar

S

S

N

O

6

Shilpa Ailawadi et al75

synthesized a series of new substituted 3,5- dimethyl

pyrazole, 3-methyl pyrazole 5- one derivative , 3- methyl- 1- (substituted phenyl)

pyrazole- 5 ones and 2,3 di methyl -1-(substituted phenyl) pyrazole 5-ones

derivatives. All the newly synthesized compounds tested for their in vivo anti

inflammatory and analgesic activity by bioassay namely Corragenan induced paw

Edema method and acetic acid induced method respectively. Compound exhibited

promising and significant inhibitory activity against COX- 2 enzyme.

7

V. H. Bhaskar, et al76

synthesized a series of pyrazole derivatives and

examined for their anti-inflammatory activity. All the compounds exhibited weak to

potent anti-inflammatory activity. Some derivatives bearing a methoxy group

exhibited very good anti-inflammatory

23

HN

N

N

N

HN

N

N

8

2.3.2 ANTIOXIDANT ACTIVITY

J.S.M. Pasin et al77

synthesized a series of pyrazole derivatives and

screened for their antioxidant activity. All compound showing good activity.

N

N

O

H2N

F F

F

9

Babu et al78

synthesized a series of pyrazoline derivatives and evaluated for

antioxidant activity at 1000, 500, 250, 100, 50, 25 and 10 mg.ml-1

concentrations

against standard drug ascorbic acid. All compounds showed excellent antioxidant

activity as compared with ascorbic acid.

24

O

HO O

NN

O

O

10

K. B. Umesha et al79

Synthesized of 5-methyl-2-(5-methyl-1,3-diphenyl-1H-

pyrazole-4-carbonyl)- 2,4-dihydro-pyrazol-3-one and evaluation of their antioxidant

activity

N

N

Ar

Ar

N

O

N

O

11

R.Suthakaran et al80

synthesized 2-[(5-substituted aryl-1’N-substituted aryl

amino methyl) pyrazol-3-yl] benzofuran by treating 2-acetyl benzofuran with

different aromatic aldehyde in the presence of a strong base to give 2-substituted

arylidene acetyl benzofuran which on condensation with hydrazine hydrate in ethanol

and glacial acetic acid yielded corresponding 2-(5-substituted aryl-4,5-dihydro

pyrazolyl) benzofuran followed by its reaction with aromatic amine and

formaldehyde in glacial acetic acid. The structures of the synthesized compound have

been established on the basis of IR, 1H-NMR and MASS spectra data Compounds

have been screened for anti-inflammatory, antioxidant and antibacterial studies. Most

25

of the compounds shown good antioxidant activity, which were comparable with that

of standard drug ascorbic acid.

HN

N

N

O

R

R'

12

2.3.3 ANTITUBERCULAR ACTIVITY

H.S.Joshi et al81

Synthesized a series of 1-acetyl-3,5-diphenyl-4,5-dihydro-

(1H) pyrazolederivatives and evaluation of their antitubercular activity

13

E.C. Coutinho et al82

Synthesized a series of N-phenyl-3-(4-fluorophenyl)-4-

substituted pyrazole derivatives and screened for their antitubercular activity. All the

synthesized compounds showed moderate to good activity.

26

14

Kini et al83

synthesized a novel series of heterocyclic o/m/p- substituted

diphenyl ether derivatives and determined their activity against H37Rv strain of

Mycobacterium. All compounds inhibited the growth at concentration as low as 1

ugml-1

.

15

Babu et al84

synthesized and evaluated a biological activity of 1, 3, 5

trisubstituted pyrazolines bearing benzofuran. They found to be anti tubercular,

antimicrobial and antiinflamatory in nature.

27

16

2.3.4 ANTITUMOR ACTIVITY

Braulio Insuasty et al85

synthesized a series of novel 3-aryl-4-(3-aryl-4,5-

dihydro-1H-pyrazol-5-yl)-1- phenyl-1H-pyrazoles and screened their antitumor

activity.

17

Hai-Liang Zhu et al86

Synthesized a series of 3-(substituted phenyl)-5-

(substituted phenyl)-4,5- dihydro-1H-pyrazole-1-carbothioamide and 1-(5-(substituted

phenyl)-3-( substituted phenyl )-4,5- dihydro-1H-pyrazol-1-yl)ethanone as anticancer

agents.

28

18 19

2.3.5 ANTIMICROBIAL ACTIVITY

Vijay V. Dabholkar et al87

synthesized a series of fused isooxazole and

pyrazole derivatives and the newly synthesized compound were screened for

antibacterial activity against Escherichia coli, Staphyllococcus aureus,

Corynebacterium diphtheriae and Proteus aeruginosa. All the synthesized

compounds showed good activity against S. aureus and against C. diphtheriae as

compared to other derivatives.

O

N ClR

20

M.M Yousef et al88

synthesized a series of some new thiazole and pyrazole

derivatives using diarylpoxylpropanone as precursor. The antimicrobial activity of

compound considered was tested on Escheria coli, Pseudomonas puticle, Bacillus

subtilis, Streptococcus lactus and Aspergillus niger. The entire synthesized

compounds showed good activity.

29

21

B. Chankantha et al89

synthesized N-cyclohexyl-5- phenyl-1-(quinolin-2-yl)-

1H-pyrazole-4-carboxamide,N-(2,6-dimethylphenyl)-5-phenyl-1-(quinolin-2-yl)-1H-

pyrazole-4-carboxamide and N,N-diethyl-5-phenyl-1- (quinolin-2-yl)-1H-pyrazole-4-

carboxamide and these compounds showed good antibacterial activity.

22 23

S. Y. Hassan et al90

found that 4-[4-Bromo-3-(4-bromophenyl)-5-(6,6-dimethyl-

4-oxo-4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-pyrazol-1-yl] benzenesulphonamide is

having good activity against Candida albicans.

30

S

N

N

HNO

O

O

H2N

Br

Br

24

Bhaskar S Dawane et al91

reported the synthesis of 1-thazolyl-2-pyrazoline

derivates. The compounds were screened for antimicrobial activity by using agar

diffusion method against Escherichia Coli, salmonella typhi, Proteus vulgaris.

R1

R2

R3

R4

O

N

N

R5

NS

HO

Cl

25

Jag Mohan et al92

reported the synthesis of 7,8- diaryl-3(2-furyl)-2,3-cis-

8,8a-tetrahydro-4H-pyrazolo[3’,4’:4,5]thiazolo[3,2-b]-s-tetrazinea and evaluated their

antibacterial and antifungal activity

31

ONH

N

N

HNS

NN

O2N

NO2

26

Sandhya Bawa et al93

reported the synthesis of 6-fluoro-2-[4-formyl-3

(substituted phenyl) pyrazol-1-yl]benzothiazoles and screened for antibacterial

activity.

F

N

S

N

N

CHO

R

27

Esvet Akbas et al94

reported the synthesis of several new pyrazolo [3,4-

d]pyridazine derivatives by the reaction 1H-pyrazole-3-carboxalic acids and various

hydrazines. The compounds were tested for antimicrobial activities.

NN

N

N

Ph

R2

R1

O

Ph

28

32

P Manojkumar et al95

synthesized a series of novel 1-(4-methyl

coumarinyl-7-oxyacetyl)-3,5-dimethyl-4(arylazo) pyrazoles and 1-(4-methyl

coumarinyl-7-oxyacetyl)-3-methyl-4(substituted phenyl) hydrazono-2-pyrazolin-5-

ones and evaluated for antibacterial and antioxidant activities. Compounds showed

good antibacterial and antioxidant activity.

HN N

N

N

O

O

H3C

O

O

OR

29

Ketan Mistry et al96

reported the synthesis of 4-[sipro-{1’-(4”-methyl

phenyl)-3’-methyl}pyrazole]-3-chloro-1-(6-nitrobezothiazole)-2-azetidinone by micro

wave technique and studied their antibacterial activity.

S

N

N

N

N

CH3

R

H3C

Cl

O

30

2.3.6 ANALGESIC ACTIVITY

K.K. Sivakumar et al97

synthesized a series of (4Z)- 3 methyl-1-[ 2 oxo-2H-

chromen-4yl) carbonyl] – 1H pyrazole -4, 5-dione4-[( 4- substituted phenyl) hydra

33

zone). The entire compounds were screened for anti-inflammatory and analgesic

activity and showed good activity.

31

L.R.S. Dias et al98

synthesized and showed (4- methylthiophen-3-yl) (1H-

pyrazol-1-yl) methanone contains good analgesic activity

32

S.K Sahu et al99

synthesized a series of Pyrazole derivative and

screened for their analgesic activity.

HN

HO

N N

N

O

O

33

34

2.3.7 ANTICANCER ACTIVITY

Mohammad S.M. Al-Saadi et al100

synthesized a series of pyrazole and

pyrazoline fused ring systems substituted with variable biologically- active chemical

species.

N

HN

S

O

O

HN

O

NH

34

R. Kalirajan, et al101

synthesized a series of pyrazole derivatives and these

derivatives showed anticancer activity

NH

N

NN

35

Peng-cheng LV et al102

synthesized a series of pyrazole derivatives. The

compounds showed high antiproliferative activity against MCF-7 with IC50 0.08 μM.

N N

H2N

S

R

36

35

2.4 SONOCHEMICAL SYNTHESIS

Most up to date ultrasonic mechanisms hand-off on transducers, which are

made out of piezoelectric materials. The support for present-day era of Ultrasound

mechanisms was made around 1880, with the revelation of the piezoelectric impact by

the siblings Pierre and Jacques Curie. Piezoelectric materials react to the requisition

of an electrical potential crosswise over inverse confronts with a modest change in

extent. In the event that the potential is rotated at high frequencies, the precious stone

changes over the electrical vigor to mechanical vibration vigor; at sufficiently high

exchanging potential, high recurrence sound (ultrasound) is produced. Nonetheless,

cavitations as a marvel was initially distinguished and reported in 1895 by

Thorneycroft and Barnaby103

. Throughout field tests of high velocity torpedo vessels,

they watched that the arrangement and breakdown of huge air pockets brought on

disintegration of boat's propeller.

In 1927, Richards and Loomis104

perceived the first compound impacts of

Ultrasound. With a few special cases, the field was very disregarded for almost 60

years. Then again, in the 1980s, sonochemistry was reborn and started to be broadly

utilized as a part of numerous diverse zones.

Fig 1: Ultrasonic frequency range

36

The explanation behind this development was the accessibility of modest and

fitting research facility gear, for example ultrasonic cleaning baths (low force) or

ultrasonic probes (high power). Since US (waves of layering and extension) is

produced by a piezoelectric earthenware in a probe or cleaning baths, it will pass

through a fluid, with the expansion cycles pushing negative force on the fluid. In the

event that this connected negative force is solid enough to break down the

intermolecular van der Waals constrain of the fluid, little cavities or gas-filled micro

air bubbles are structured.

Cavitation is considered as a nucleated process, meaning that these

micrometer-scale bubbles will be formed at pre-existing weak points in the liquid,

such as gas-filled crevices in suspended particulate matter or transient micro bubbles

from prior cavitationevents. Most liquids are sufficiently contaminated by small

particles that cavitations can be readily initiated at moderate negative pressures. As

micro bubbles are formed, they absorb energy from US waves and grow. However, it

will reach a stage where it can no longer absorb energy efficiently. Without the

energy input, the cavity can no longer sustain itself and implodes. It is this implosion

of the cavity that creates an unusual environment for chemical reactions. There are a

few factors that can affect the efficiency of bubble collapse, such as105

,vapour

pressure, temperature, thermal conductivity, Surface tension and viscosity, the US

frequency and acoustic intensity

Since the wavelength of US between successive compression waves measures

approximately from 10 to 10-3

cm, it does not directly interact with molecules to

induce chemical change. Basically, two theories have been proposed to explain the

effect of cavitation on chemical reactions.

37

1. The ‘hot spot’ theory106

and

2. Electrical microdischarge107

theory. Because the latter is not well established,

it willnot be discussed in this review; however, it cannot be entirely ruled out

due to the complex nature of cavitation.

The ‘hot spot’ theory relies on bubble collapse in the liquid to produce

enormous amounts of energy from conversion of the kinetic energy of liquid motion

into heating of the bubble contents. Compression of the bubbles during cavitation is

more rapid than thermal transport, resulting in the generation of short-lived localized

hot spots. Experimental results have shown that these bubbles have temperatures

around 5000 K, pressures of approximately 1000 atm, and heating and cooling rates

above 1010 K/s.

The accessibility of numerous publications reviews and books obviously

to call attention to the effect of ultrasound on organic synthesis in the previous 30

years. Then again, to the best of our learning, there is one and only survey, dated

1989, that solely portrays the utilization of ultrasound in heterocyclic chemistry108

. In

this audit, we will talk over just the amalgamation of heterocyclic compounds

utilizing ultrasound energy.