Airo International Research Journal
Volume XIII, ISSN: 2320-3714
December, 2017
Impact Factor 0.75 to 3.19 UGC Approval Number 63012
154
GREEN APPROACHES ON THE SYNTHESIS OF BIOLOGICALLY
IMPORTANT HETEROCYCLES WITH BIOSURFACTANT
Shiv Pratap Shukla
Research Scholar OPJS University Supervisor Name- Satay Vir Singh
Designation- asst. Professor
ABSTRACT
The idea of recoup and reuse has been developed and effectively rehearsed at Sangamner College in
this manner decreasing the necessity of CTC for leading Partition coefficient of Iodine among water
and CTC analyze. The measures of KI to be utilized in various Iodometric titrations are advanced
consequently the analyses become financially savvy and pollution load by profluent additionally gets
diminished. The gushing containing iodides can be dealt with and oxidized to recover Iodine by
basically going air through it for shorter time in nearness of an impetus. The synthesis of nitro, chloro
and bromo subordinates of straightforward beginning compounds are performed by making
adjustment in the detailed reagents/methods in the light of Green chemistry viewpoints and the items
are recognized by examination with known dissolving focuses and furthermore contrasting the IR
Spectral data of certain items with SDBS data.
KEYWORDS: Pyrazolones, Green Approaches, Synthesis, Biologically, Heterocycles, Bio-
surfactant
INTRODUCTION
Knoevenagel condensation is a standout
amongst the most flexible carbon-carbon bond
framing reactions in the natural synthesis
named after scientist Emil Knoevenagel
reaction has assortment of applications in
exquisite synthesis of fine chemicals, synthesis
of carbocyclic and heterocyclic compounds
and in hetero Diels-Alder reaction. The
Knoevenagel condensation items are not just
the key moderate for the synthesis of natural
and restorative medications, polymer,
cosmetics and perfumes yet additionally have
far reaching applications including restraint of
antiphosphorylation of EGF-receptor and
antiproliferative movement , Generally,
Knoevenagel reaction is done by a
nucleophilic option of dynamic methylene
compounds like malononitrile, barbituric acid,
Meldrum's acid, indoles and 1, 3-indanediones
to carbonyls pursued by dehydration to give
alpha, beta conjugated enones and in this
manner it is the best method for the
arrangement of substituted alkenes.
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
December, 2017
Impact Factor 0.75 to 3.19 UGC Approval Number 63012
154
Fig. Active Methylene Molecules
In view of the chemistry and exceedingly
articulated pharmacological properties shown
by Knoevenagel products, have made them
alluring manufactured targets which can be
promptly acknowledged from the presence of
tremendous number of articles managing
synthesis and biological exercises of these
subsidiaries. Chen and gathering revealed
condensation of fragrant aldehydes with
dynamic methylene compounds like
malononitrile, barbituric acid, Meldrum's acid
in water utilizing triethylbenzylammonium
chloride as catalyst.
Fig. uncatalysedKnoevenagel condensation of aromatic aldehydes
In 2005, Deb and colleagues were fruitful in
completing uncatalysedKnoevenagel
condensation of sweet-smelling aldehydes
with dynamic methylenes in water at room
temperature . During a decade ago ionic fluids
have risen as green options in contrast to
unpredictable organic solvents and are utilized
as recyclable catalysts. Jana et at.] imagined
task explicit ionic fluid [bmIm]OH for
Knoevenagel condensation of sweet-smelling
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
December, 2017
Impact Factor 0.75 to 3.19 UGC Approval Number 63012
155
just as aliphatic aldehydes with dynamic
methylenes which demonstrated general
relevance of convention . Product et al.
effectively done Knoevenagel condensation
reaction utilizing l,8-diazabicyclo[5.4.0]undec-
7-ene (DBU) as fundamental catalyst under
solvent free conditions at encompassing
temperature.
Solvent free Knoevenagel condensation
reaction has been additionally revealed by
Suresh and associates in nearness of alum as
modest and effectively accessible catalyst
Wang and colleagues built up a proficient
protocol for condensation reaction of aryl
aldehydes with malononitrile utilizing
reasonable and effectively accessible inorganic
zinc salts, for example, Zn(0Ac)2.2H20,
ZnCl2 and ZnBr2 under solvent free
conditions and detailed microwave helped
Knoevenagel condensation under solvent free
condition utilizing natural fundamental
heterogeneous catalyst hydroxyapatite
[Caio(P04)6(OH)2] (p-HAP) and depicted its
instrument as appeared.
Amino acids are organic atoms so far been
utilized as chiral helpers, chiral ligands and
chiral synthons for natural products and
medications. Organocatalysts like proline have
been broadly revealed as catalysts in organic
synthesis. Rahmati et al. researched job of
organocatalysts, for example, L-Histidine and
L-Arginine in Knoevenagel condensation.
Deshmukh and partners detailed exceedingly
effective and green reaction of aryl aldehydes
with malononitrile in nearness of lemon
squeeze as biocatalyst. Lemon has a place with
the citrus family and contains citrus extract in
5-7 %. Because of the acidic nature (pH 2-3)
ofjuice, reaction continued proficiently.
Polyacrylonitrile fiber has been utilized in
attire industry as a fabric material since it is
consumption and mold safe and has
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
December, 2017
Impact Factor 0.75 to 3.19 UGC Approval Number 63012
155
magnificent mechanical quality. It has
additionally heaps of eyano groups which can
be changed into carboxyl, amide or
amodoximes groups and it is appropriate for
getting ready fiber catalyst.
Triethelynetetramine energized fiber catalyst
has been proposed to catalyze condensation of
aryl aldehydes with dynamic methylenes by Li
and group.
Fig. Preparation Of Amine Functionalised Fiber Catalyst
The potential utilization of ionic liquid 1-
methylimidazolium trifluoroactate [Hmim]Tfa
has been abused in synthesis of alkenes from
aryl aldehydes and Meldrum's acid by
Darvatkar and partner.
Wilson et al. detailed Knoevenagel reaction of
Meldrum's acid and sweet-smelling aldehydes
utilizing synergist sum ofpiperidine and
[bmim]PF4 as recyclable reaction medium.The
mellow, green and effective synthesis of 2,2-
dimethyl-5-[(4-oxo-4f/ - chromen-3-
yl)methylene]-l,3-dioxane-4, 6-diones has
been accomplished by Shelke et al. from 4-
oxo-4ff-benzopyran-3-carbaldehydes and
Meldram's acid. l-Benzyl-3-
methylimidazolium chloride [bnmim](Cl)
utilized as recyclable ionic liquid
.
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
December, 2017
Impact Factor 0.75 to 3.19 UGC Approval Number 63012
154
Cellulose is a biopolymer and is utilized as
help material for different catalysts. They have
drawing in highlights over the organic and
inorganic backings, for example, they are very
inactive, reasonable, biodegradable and
naturally amiable and the most plenteous
sustainable material. Shelke and group
investigated condensation of 3-
formylchromone/2-chloroquinoline-3-
carbaldehyde with Meldrum's acid/ethyl
cyanoacetate utilizing recyclable bio-upheld
cellulose sulphuric acid by pounding under
solvent free conditions. Thirupathi and group
misused L-Tyrosine catalyzed Knoevenagel
reaction of aryl aldehydes and Meldrum's acid
by crushing under solvent free condition. This
bifunctional, zwitterionic catalyst utilized is
effective and naturally benevolent.
Microwave-helped organic synthesis has
pulled in significant consideration since it
prompts diminished reaction time, expanded
yield and simpler work-up. In 2001, Ali and
partners showed microwave helped
Knoevenagel condensation of barbituric acid
and fragrant aldehydes over essential alumina.
In our research center, Salunkhe effectively
connected the novel concept of Gel Entrapped
Base Catalyst for Knoevenagel condensation
of dynamic methylenes like barbituric acid and
Meldrum's acid with aryl aldehydes. These
catalysts are set up by entangling bases in
watery gel framework of agar-agar which is a
polymer made out of rehashing agarobiose
units shifting back and forth between 3-
connected Dgalactopyranosyl (G) and
4dinked-3 6-anhydro-«-L-galactopyranosyl
(LA) units. The utilization of GEBC
diminishes the amount of bases and
furthermore gives recyclability to the
procedure.
Nagarajeffectively done the reaction of
unsaturated aldehydes with barbituric acid
which managed biologically significant
products. The reaction was completed under
non-synergist and solvent free microwave
illumination
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
December, 2017
Impact Factor 0.75 to 3.19 UGC Approval Number 63012
154
.
Jain and colleagues completed spearheading
work to integrate indole substituted alkenes
from indole aldehyde and different dynamic
methylene compounds utilizing microwave
illumination and L-proline as catalyst.
Integrated compounds screened for
antibacterial movement.
Dubey et al. additionally arranged novel indole
alkenes with 3-cyanoacetylindole (2) as
dynamic methylene compound utilizing
triphenylphosphine catalyst at room
temperature and blended novel alkenes (3 and
5) utilized further to respond with DMS in
PEG-600 to bear the cost of N,N*dimethyl (6)
subordinates.
In spite of the fact that Knoevenagel
condensation reaction appreciates a rich
cluster of reports with respect to the differing
dynamic methylene compounds, not many
articles are accounted for in regards to
indanedione subsidiaries in writing. 1,3-
indanedione is a fragrant transfixed/?-
diketone, a yellow strong. It very well may be
set up by decarboxylation of the sodium salt of
2-etoxycarbonyl-l,3-indandione, which itself is
acquired by Claisen condensation of ethyl
acetic acid derivation and dimethyl phthalate.
Airo International Research Journal
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Certain subordinates of 1,3-indanedione are
utilized in human medicine which goes about
as Vitamin K opponent anticancer, pain
relieving, mitigating, fungicidal and
bactericidal agents. Phenindione (an) is an
anticoagulant which functions as Vitamin K
enemy. Ciorindione (b) is subsidiary of
Phenindione. Diphenandione (c) likewise has
anticoagulant impacts and is utilized as
rodenticide against rodents, mice, voles,
ground squirrels and different rodents. It has
longer movement than warfarin and other
engineered indanedione anticoagulants.
Fig. Derivatives of 1,3-indanedione
2-Arylideneindane-l,3-dione frameworks are
modernly significant antecedents since they
are utilized as intermediates for the synthesis
of various bio-dynamic particles. Just as they
have significant pharmacological exercises, for
example, anticoagulants and cytotoxics. Not
many reports are accessible for the synthesis
of these subsidiaries. A great course for the
synthesis of these subordinates is Knoevenagel
condensation of 1,3-indanedione with aryl
aldehydes. The vast majority of the detailed
methods work under reflux conditions utilizing
different catalysts including acids or bases. In
1998, Bullington and colleagues detailed the
synthesis of 2-arylideneindane-l,3-diones
under the reactant activity of vaporous HC1
and p-TSA under reflux condition. Wu and
partners built up a productive method for the
synthesis of 2-arylideneindane-l,3-diones by
condensation reaction of 1,3-indanedione and
fragrant aldehydes utilizing pounding method
at room temperature. Silica gel and MgO were
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utilized as fundamental catalysts for this synthesis.
Karthik et al. revealed 2-arylideneindane-l,3-
diones synthesis under reflux condition in
ethanol utilizing piperidine. This protocol
further reached out to integrate spirooxiranes
and assessed their enemy of tubercular
movement Synthetic course to get ready
arylideneindane-1,3-diones was given by
Katarzyna and associates utilizing acidic acid
and concentrated H2S04. Incorporated
subsidiaries further screened for anticoagulant
movement. As of late, Yang et al. revealed
catalyst free course for synthesis of 2-
arylideneindane-1,3-dione subordinates in
refluxing water. The exhibited method is dull
and includes long reaction times.
SYNTHESIS OF PYRAZOLONES BY
TANDEM KNOEVENAGEL-MICHAEL
REACTION
Heterocyclic compounds happen broadly in
nature and are basic to life. Nitrogen
containing heterocycles establish the biggest
bit of concoction substances, which are a piece
of numerous natural products, fine chemicals
and biologically dynamic pharmaceuticals
basic for upgrading the personal satisfaction.
High-throughput screening and disposal of
indiscriminate hits prompted the explanation
of one hit class for example pyrazoles.
Pyrazole and its subsidiaries, a class of surely
understood nitrogen containing heterocyclic
compounds, involve a significant position in
medicinal and pesticide chemistry with wide
scope of bioactivities .Pyrazolone, subordinate
of pyrazole is five-membered lactam ring
compound containing two nitrogens and
ketone in a similar particle with atomic
formula of C3H4N2O. There are two potential
isomers: 3-pyrazolone and 5-pyrazolone.
Pyrazolone is an active moiety as
pharmaceutical ingredient and refers to
nonsteroidal anti-inflammatory drugs
(NSAID) used in the treatment of arthritis and
other musculoskeletal and joint disorders.
Pyrazolone class includes phenylbutazone (I),
oxyphenbutazone (II), dipyrone (III) as bio-
active molecules. Phenazone or antipyrine is
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
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Impact Factor 0.75 to 3.19 UGC Approval Number 63012
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an analgesic and antipyretic (IV). Pyrazolone
derivatives, as lactam structure related
compounds, are also widely used in preparing
dyes and pigments. For example, l-(2-
chlorophenyl)-3-methyl-5-pyrazolone (V) is
used as an intermediate to prepare dyes and
pigments. 4-Aminoantipyrine or ampyrone
(VI) possibly can be used as an intermediate
for the synthesis of pharmaceuticals especially
antipyretic and analgesic drugs. It is also used
in the colorimetric determination of phenols.
Presently days, the pyrazolone subsidiaries
have been given much consideration in light of
their hopeful biological exercises, for example,
antitumor, particular COX-2 inhibitory,
cytokine inhibitors ,Moreover, they are fit for
prototropictautomerism and can be utilized as
chelating agents for some metal particles and
ligands ,2,4-Dihydro3H-pyrazol-3-one
subordinates including 4,4'-
(arylmethylene)bis(3-methyH-
phenyllHpyrazol-5-ols) being utilized as
gastric secretion stimulatory, energizer,
antibacterial and antifilarial agents ,
furthermore, they are likewise connected as
fungicides, pesticides, bug sprays and
dyestuffs.
Wang et al. revealed the ecologically amicable
synthesis of 3-methyl1-phenyl-5-pyrazolone
with fragrant and aliphatic aldehydes in water
at refluxing temperature utilizing sodium
dodecyl sulfate (SDS) as the surfactant
catalyst.
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
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In 2008, Elinson and partners incorporated
these subordinates utilizing electrolysis
method,Recently, the utilization of ceric
ammonium nitrate has gotten significant
consideration as it is an economical, non-
dangerous catalyst for different organic
changes giving brilliant yields. K. Sujatha and
group built up an effective and ecofriendly
method for the synthesis of 4,4'-
(arylmethylene)bis(lflr-pyrazol-5-ols) by pair
Knoevenagel-Michael reaction in nearness of
ceric ammonium nitrate (CAN) in water at
encompassing temperature and furthermore
represented its system Synthesized compounds
additionally assessed for ki vitro antiviral
action against peste des petits ruminant
infection (PPRV).
Natural biopolymers are appealing applicants
in the quest for strong help and give reusable
and heterogeneous structure to catalyst
planning and can be proficiently utilized in
organic reactions as it very well may be
effectively isolated, reused and not tainted by
the products. In this connection, Mosaddegh
arranged a cheap biopolymer-based catalyst
cellulose sulfuric acid (CSA) and effectively
connected for synthesis of pair Knoevenagel-
Michael reaction.
K. Niknam and colleagues created upheld
silica-fortified S-sulfomc acid (SBSSA) and
utilized as recyclable catalyst for the
condensation reaction of sweet-smelling
aldehydes with 3miethyl-l-phenyl-5-
pyrazolone. This condensation reaction was
performed in ethanol under refluxing
conditions giving 4,4'- ulkylmethylene-bis(3-
methyl-5-pyrazolones) in 75-90% yields.
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
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Impact Factor 0.75 to 3.19 UGC Approval Number 63012
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Fig. silica-bonded S-sulfomc acid (SBSSA)
The examination of ionic liquids is created at a
blasting pace during past decade due to their
properties, for example, functional
nonvolatility, low liquefying point just as great
electrochemical and warm strength. Zang
detailed a startling synthesis of 4-[(5-hydroxy-
3-methyl-l-phenyl-l/f-pyrazol-4-yl)-
phenylmethyl]-5-methyl-2-phen-yl-l,2-
dihydro-pyrazol-3-ones through the
condensation reaction of arylaldehydes and 3-
methyl-l-phenyl-5-pyrazolone without
precedent for the nearness of Br^nsted acidic
ionic liquid [HMIM]HS04 in refluxing ethanol
Same group announced this synthesis at
surrounding temperature with the guide of
ultrasound system as it has been considered as
a perfect and helpful protocol when contrasted
with conventional methods as a result of the
ordinary highlights, for example, quickening
organic reactions, simpler control and being
increasingly advantageous.
Silica sulfuric acid (SSA) has been broadly
utilized as reusable, heterogeneous, modest,
strong Bronsted acid catalyst. This
heterogeneous catalyst can be effectively
isolated from the reaction media, has more
noteworthy selectivity, recyclable, simpler to
deal with, increasingly steady, nontoxic, and
insoluble in organic solvents. Niknam and
partners used this silica sulfuric acid (SSA) for
the condensation reaction of fragrant
aldehydes with 3-methylT-phenyl-5-
pyrazolone in water-ethanol (1:1) at 70 °C.
In 2012, Niknam and partners visualized A-(3-
silicapropyl)-/V-methyl imidazolium hydrogen
sulfate ([Sipmim]HS04) as heterogeneous
strong acid catalyst and connected for the
synthesis of 4,4'- alkylmethylene-bis(3-
methyl-5-pyrazolones) by couple
Knoevenagel-Michael reaction in refluxing
ethanol. A. Khazaei et al. unveiled a green,
straightforward and productive method for the
synthesis of 4,'4'- (arylmethylene)-bis(3-
methyl-l-phenyl-1/ - pyrazol-5-ol)s by the
condensation of l-phenyl-3-methylpyrazol-5-
one with sweet-smelling aldehydes utilizing
1,3-disulfonic acid
imidazoliumtetrachloroaluminate
{[DsimJAlCU] as new, heterogeneous and
reusable catalyst
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154
.
CONCLUSION
Our engineered pathway agrees to a few key
prerequisites of green chemistry standards, for
example, end of organic solvents, practically
nil squander, straightforward stir up method
and non-toxic, safer response medium
alongside excellent recyclability of
biosurfactant. Significance of indiscrimination
idea in biocatalysis is imperative, since it
features the current impetuses, yet may give
novel and practical manufactured pathways
which are not at present accessible. The
utilization of basic experimental method and
simplicity of recuperation and reuse ofthis
novel response media is relied upon to add to
the development of green system for the
development of biologically dynamic
pyrazoles. The present protocol permits quick
and effective synthesis of out of reach
pyrazoles offering alluring highlights, for
example, no utilization of impetus, diminished
response time, simple stir up methodology,
non-toxic and safer response medium giving
significant returns. Taking everything into
account, an exceedingly proficient
methodology for the multi-part synthesis of
tetrahydrobenzojpyrans utilizing the
synergistic impact of ultrasound and novel ILs
dependent on DABCO system has been set up.
REFERENCES
[1]. Shukla S. K., Tiwari V.K., Rani S.,
Ravikan, Tewari I.C., (2011),
International Journal of Agriculture
Sciences, 3(3): 121-127.
[2]. Ali Z. Y., Mohamed S. A., Edrees M.
M., (2012), Nature and Science, 10(7):
1-12.
[3]. Benjamin E., Hijji Y., (2008),
Molecules, (13): 157-169.
[4]. Vitnic V. D., Popovik-Dordevikc J.
B., Vitnik Z. J., Ivanoic M. D., Juranic
I. O., (2012), University of Belgrade,
Serbaria, (B-06-P): 88-90
[5]. Fortuna C. G., Barresi V., Musso N.,
Musumarra G., (2009), ARKIVOC,
(viii): 222-229
[6]. Shetgiri N.P., Nayak B.K., (2005),
Indian Journal of Chemistry, 44B:
1933- 1936.
[7]. Blanco M. M., Salerno A., Perillo I.
A., (2010), ARKIVOC, (xi): 215-231.
[8]. Ulianas A., Heng L. Y., Ahmad M.,
(2012), Sensors, (11): 8323-8338.
[9]. Prezhdo V. V., Kowalski P.,
Kowalska T., Zubkova V.V., Olan K.,
Prezhdo O.V., (2011), Journal of
Molecular Structure, (997): 20-29.
[10]. Rajput A. P., Girase P. D.,
(2012), International Journal of
ChemTech Research, 4(2): 634-639.
[11]. Sharma R.N., Sharma K.P.,
Dixit S.N., (2010), International
Journal of Chem Tech Research, 2(2):
800-806
[12]. Rajput A. P., Rajput S. S.,
(2009), International Journal of
PharmTech Research, 1(3): 900-904.
Airo International Research Journal
Volume XIII, ISSN: 2320-3714
December, 2017
Impact Factor 0.75 to 3.19 UGC Approval Number 63012
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[13]. Mosaddegh E., Hassankhani
A., Mansourie G., (2011), Journal of
Chemistry, 8(2): 529-534