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.