GREEN APPROACHES ON THE SYNTHESIS OF BIOLOGICALLY ... · Knoevenagel reaction is done by a nucleophilic option of dynamic methylene compounds like malononitrile, barbituric acid,

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.



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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



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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



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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

.



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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



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.

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.



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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



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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.



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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.



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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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.

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.

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Documents

GREEN APPROACHES ON THE SYNTHESIS OF BIOLOGICALLY ... · Knoevenagel reaction is done by a nucleophilic option of dynamic methylene compounds like malononitrile, barbituric acid,