9

REVIEW OF LITERATURE

Pesticides use continues to rise even though public pressure has increased against

their continued widespread application. Historians have traced the use of pesticides to

the time of Homer around 1000 B.C., but the earliest record of insecticides pertain to

the burning of “Brimstone” (Sulfur) as a fumigant. In was World War II that opened

the modern era of chemical control with the introduction of new concept of insect

control: synthetic organic insecticides (Ware and Whitcare, 2004). In 1970 U.S.

production of pesticides and related products amounted to 1034 billion 1b with sales

valued at $ 870 million. Perhaps the most impelling reasons for continued widespread

use of pesticides is their continued availability, convenience and dramatic

effectiveness in dealing with the pest problem on a short-term basis. Over 900 basic

chemicals are used to formulate thousands of synthetic commercial pesticides

(Marderoslan, 1975).

Pesticides have had a significant impact on agriculture by increasing crop production,

on human health by decreasing diseases such as malaria, yellow fever and bubonic

plague and on economics by decreasing the work force needed to produce food. The

use of pesticides in agriculture has reached a plateau over the last 15 years and is

beginning to decrease, because plants are being genetically engineered (GMOs, or

genetically modified organisms) to require less pesticides (Curtius, 2001).

Mortality attributed to accidental poisoning by pesticides has declined during 1960’s

and 1970’s. Traditionally, new pesticides have been discovered by synthesis, bioassay

and evaluation. The wide use of pesticides has led to the enactment at all levels (e.g.:

local, state and federal) of legislation which has undergone numerous changes in

recent years. Interest in pesticides extends beyond their use simply to increase crop

yields, specifically in their use in the control of pests as vectors of disease.

Most of the pesticidal agents are associated with different types of adverse effects in

agriculture, environment, food and medical sciences and human beings. Many

pesticidal agents have been banned due to their harmful effects in human beings and

environment and resistance developed in pests against these agents such as DDT and

related compounds.

10

Different organizations like EPA, IPM, NPIC have been established, which monitor

the harmful effects of these pesticides and devise ways and means to protect the

environment and human beings. Development of safer pesticides is also the aim of

these organizations.

Pesticides are classified in two categories: -

1. Chemical Pesticides

These substances are synthesized in the laboratory. Some examples are

organophosphates, organochlorines, carbamates, pyrazoles, neonicotinoids etc.

2. Biopesticides

Pesticides derived from such natural materials as animals, plants, bacteria and

certain minerals. For example, canola oil and baking soda have pesticidal

applications and are considered biopesticides. Biopesticides fall into three major

classes:

a) Microbial Pesticide

Microbial pesticides consist of a microorganism (e.g.: a bacterium, fungus, virus

or protozoan) as the active ingredient. These pesticides can control many

different kinds of pests, although each separate active ingredient is relatively

specific for its target pest [s]. For example, there are fungi that control certain

weeds, and other fungi that kill specific insects.

b) Plant Incorporated–Protectants (PIPs)

They are pesticidal substances that plants produce from genetic material that

has been added to the plant. For example, scientists can take the gene for the

Bt pesticidal protein, and introduce the gene into the plant’s own genetic

material. Then, the plant, instead of the Bt bacterium, manufactures the

substance that destroys the pest.

c) Biochemical Pesticides

11

These are naturally occurring substances that control pests by non-toxic mechanisms. Biochemical pesticides include substances, such as insect sex pheromones, that interfere with mating as well as various scented plant extracts that attract insect pests to traps.

Some of the chemical pesticides with their chemical names, structures and their modes of action (Ware and Whitcare, 2004; Curtius, 2001) are listed below:

S. No. Chemical Class Chemical Name Structure Activity

1 Neonicotinoids

Imidacloprid

1-(6-chloro-3-pyridinylmethyl)-N-nitroimidazolidin-2-ylideneamine

Insecticidal

Acts by deranging the reflexes and autonomic behaviour of the insect nervous system, causing them to fail to carry out their normal pattern of behaviours, for instance feeding or moulting.

12

Nicotine (S)-3-(1-methylpyrroli-din-2-yl)pyridine

Insecticidal It blocks the nicotinic acetylcholine receptor. It increases the heart rate, blood pressure and reduces the appetite.

2 Organochlorines

DDT

Dichlorodiphenyl trichloroethane

Insecticidal

The mode of action of DDT has never been clearly established. But in some complex manner it destroys the delicate balance of sodium and potassium iona way to that prevents normal transmission of nerve impulses in both insects and mammals.

Benzenehexa Chloride

Hexachlorocyclohexane Cl Cl

Cl

ClCl

Cl

fungicidal

It causes poryhyria by partially blocking haem biosynthesis, leading toexcretion of uroporyphyrin. The involvement of reactive toxic metabolites like pentachlorophenol has been suggested.

13

3. Cyclodienes

Aldrin

(IR, 4S, 4as,5S, 8R, 8a R)-1,2,3,4,10,10-hexa-chloro-1,4,4a,5,8, 8a-hexa-hydro, 1,4: 5, 8c)-dimethanonaphtha-lene

CH2

Cl

Cl

Cl

Cl

CCl2

Insecticidal, termiticidal

Their modes of action are not clearly understood.

However, it is known that these acts on the

inhibitory mechanism called the GABA receptor.

They prevent chloride ions from entering the

neurons and thereby an

of GABA.

Dieldrin 1,2,3,4,10,10-hexachloro-6-7-epoxy-1,4,4a,5,6,7,8, 8a,-octahydriendo 1,4-exo -5,8-dimethanonapthalone

CH2

Cl

Cl

Cl

Cl

CCl2O

Insecticidal, termiticidal

4. Organosphosphate

s

Parathion

0,0-Diethyl-0-(4-nitrophenyl) phosphoro-thioate

Insecticidal They work by inhibiting certain enzymes of the

nervous system, namely ChE. The enzyme is said

to be phosphorylated, when it becomes attached to

the phosphorus moiety of the insecticide, a binding

i.e. irreversible. The inhibition results in the

accumulation of acetylcholine (Ach) at the

neuron/neuron and neuron/muscle

(neuromuscular) junctions or synapses, causing

twitching of voluntary muscles and finally

paralysis.

Diazinon (Basudin)

O-isopropyl-4-methyl-6-pyrimidinyl phosphor-othionate

Insecticidal

Fosthiazate (RS)-3[sec-butylthio (ethoxy) phosphinoyl]-1,3-thiazolidin-2-one. N

S

O

S – CHCH2–CH3

S

P–O – CH2–CH3

CH3

nematicidal

14

5. Pyrazoles

Fipronil

5-amino-1-(2,6-dichloro -,-trifluoro--tolyl)-4-trifluoromethyl-sulfinyl pyrazole-3-carbonitrile

Insecticidal

It blocks the GABA regulated chloride channel in

neurons, thus antagonizing the “calming” effects

of GABA.

Tebufenpyrad N-(4-tert-butylbenzyl)-4-chloro-3-ethyl-1-methylpyrazole-5-carboxamide.

Insecticidal

It inhibits mitochondrial electron transport at the

NADH-CoQ reductase site; leading to the

disruption of adenosine triphosphate formation, the

crucial energy molecule.

6. Carbamates

Carbaryl

1-naphthalenyl methylcarbamate

Insecticidal

They inhibit ChE enzyme as OPs do, and they behave in almost identical manner in biological systems, but with two main differenccarbamates are potent inhibitors of aliesterase and their selectivity is sometimes more pronounced against the ChE. Second ChE inhibition by carbamates is reversible. When ChE is inhibited by carbamate, it is said to be carbamylated. In insects, the effects of carbamates are primarily those of poisoning the CNS, since the insect neuromuscular junction is not cholinergic, as in mammals.

Carbofuran 2,3-dihydro-2-2-dimethyl-7-benzofuranylmethylcar-bamates O

CH3

CH3

O C N CH3

HO

Insecticidal

7. Pyrethroids

Fluvalinate

(RS)--cyano-3-phenoxybenzyl N-(2-chloro--trifluoro-p-tolyl-1)-1-valinate.

Insecticidal They act on both the peripheral and central

nervous system and initially stimulate nerve cell

to produce repetitive discharges and eventually

cause paralysis. Fenvalerate Cyano (3-phenoxyphen-yl) methyl 4-chloroal-pha (1-methylethyl) benzene acetate

Insecticidal

8. Pyrrole

Chlorfenapyr

4-bromo-2-(4-chloro-phenyl)-1-ethoxymethyl -5-trifluoromethyl-pyrrole-3-carbonitrile

Insecticidal It is an “uncoupler” or inhibitor of oxidative

phosphorylation, preventing the formation of ATP.

15

9. Miscellaneous

Fluquinconazole

3-(2,4-dichlorophenyl)-6-fluoro-2-(1H,1,2,4-triazol-1-yl)quinazolin 4(3H)-one.

fungicidal

It acts by inhibiting the demethylase enzyme

involved in sterol biosynthesis in the susceptible

fungi

Simetryn N2, N4-diethyl-6-methylthio-1,3,5-triazine-2,4-diamine

N

N N

NH

CHCH3

NH CH2CH3

SCH3

herbicidal

Photosynthetic electron transport inhibitor at the

photosystem II receptor in the xylem, and

accumulation in the apical meristems.

16

Mefenpyr (RS)-1-(2,4-dichlorophenyl)-5-methyl-2-pyrazoline-3,5-pyrazoline-3,5-dicarboxylic acid.

herbicide safener

It is an inhibitor of fat (lipid) synthesis.

Chlorflurazole 4,5-dichloro-2-trifluoromethylbenzimi dazole.

herbicidal, insecticidal

Affect both the PNS and CNS of the insect. It

initially stimulates nerve cells to produce repetitive

discharges and eventually cause paralysis acts on

the channel in the brain.

Atrazine 6-chloro-N-ethyl-N-isopropyl-1,3,5-triazine-2,4-diamine

herbicidal

It is strong inhibitor of photosynthetic electron transport.

Benomyl Methyl-1[(butylamino) carbonyl]-1H-benzimi-dazole-2ylcarbamate

fungicidal

It binds to microtubuli, an essential structure of all cell, thereby interfering with their functions cell division, intracellular transport etc. Selective toxicity of benomyl is thought to be due to its higher affinity for fungal as compared withmammalian microtubuli.

Besides insectcides and herbicides, the pesticides includes fungicides, bactericides because both fungi and bacteria are known to destroy crops and food material. The basic ways to control these microorganisms is by killing or by inhibiting the growth of fungus and bacteria.

The following table consists of few of the antifungal (John, 2001; Marderoslan, 1975) and antibacterial (William, 2001; Henry, 2001; William 2001) agents with their chemical names, structures and modes of action, which are summarized below:

S.No. Chemical Class Chemical Name Structure Activity

17

1. Imidazoles and

Triazoles

Ketoconazole

1-[4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxol n-4-yl] methoxy]phenyl] piperazin-1-yl]ethanone.

Antifungal

Itraconazole 4-[4-[4-[4-[[2-(2,4-dichlorophenyl-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy] phenyl]piperazin-1-yl]phenyl]-1-sec-butyl-1,4-dihydro-1,2,4-triazol-5-one.

Antifungal

Fluconazole 2-(2,4-Difluro-phenyl)-1,3-bis-[1,2,4]triazol-1-yl-propan-2-ol

N

NN

OHNN

N

F

F

Antifungal

18

Clotrimazole 1-(2-chlorotrityl)imidazole

Antifungal

Miconazole [C1-[2-(2,4-Dichlorophenyl)-2-(2,4-dichlorophenyl)methoxy] ethyl]-1H-imidazol)

Antifungal

2. Polyenes

Amphotericin B

33-4-Amino-3,5-dihydroxy-6-methyl-tertahydropyran-2-yl)oxy-1,3,5,6,9,1,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo [33.31]non atriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid.

Antifungal

Flucytosine (5-Flurorcytosine;5-FC;4-amino-5-fluoro-2-pyrimidone)

Antifungal

19

3. Griseofulvin (2S,6R)-7-chloro-2,4,6-trimethoxy-6-methyl-3H, 4H-spiro[1-benzofuran-2,1-cyclohex[2]ene-3,4-dione.

Antifungal

4 Aminoglycoside

s

Streptomycin

O-2-Deoxy-2-(methylamino)-d-L-glycopyranosyl-(12)-0-5-deoxy-3-c-formyl-d-L-lyxofuranosy19(14)-N,N-bis(aminoimino-methyl)-D-streptamine

H NHCNH2

OH H

H

OH H

NH

H

H

NH

H2NC

NH

O O

H

H

OH

CHO H

O

H3C

R=CH3NH

StreptidineHO

OH

CH2OH

H

OH

R

H

H H

HO

Antibacterial

20

Gentamicin O-3-deoxy-4-c-mehyl-3-(substitutedamino)--L-orabinophyanosyl-(16)-o-[2,6-diamino-2,3,4,6-tetradeoxy--D-erythro-hexapyranosyl-(14)]-2-deoxy-D-streptamine.

OR

O

NH2

OH

O

NH2

O

HO

NHCH3H3C

H2N

HO

R=CH2NH2, CH3CHNHCH3 etc.

Antibacterial

5. Quinolones

Ciprofloxacin

1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid.

Antibacterial

Gatifloxacin 1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1H-quinoline-3-carboxylic acid.

Antibacterial

21

6. Chloramphenicol

2,2-Dichloro-4-(a-R, p-R)-p-hydroxy-a-hydroxymethyl-4-nitrophenethyl-acetamide

Antibacterial

7. Cephalosporins

Cephalexin

7-(D-2-amino-2-phenylaceta-mido)-3-methyl-8-oxo-5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid.

Antibacterial

Ceftrioxane

(6R,7R)-7-[(2-Amino-4-thaiz-olyl)glyoxylamido]-8-oxa-3-[[(1, 2,5,6-tetrahydro-methyl-5,6-dioxo-as-triazin-3-yl)thio]meth-yl]-5-thia-1-azabicyclo[4.2.0] oct-2-ene-carboxylic acid.

Antibacterial

8. Sulphonamides

Sulfadiazine

4-Amino-N-2-pyrimidinyl-benzenesulfonamide

Antibacterial

Sulfanilamide

4-Aminobenzenesulfonamide

Antibacterial

22

9. Penicillins

Penicillin G

3,3-Dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

Antibacterial

Penicillin V 3,3-Dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

Antibacterial

Ampicillin 4-Thia-1-azabicyclo[3,2,0] heptane 2-carboxylic acid.

Antibacterial

In addition of the above known agents a plethora of compounds have been

synthesized and evaluated for insecticidal, antifungal and antibacterial activities by

different scientists which are summarized as follows:

23

BENZOIMIDAZOLE DERIVATIVES

The efficiency of azole derivatives as chemotherauptic agents and their chemisty has been extensively

studied. In the past years, the literature is enriched with progressive findings about the synthesis and

pharmacological actions of fused heterocycles. Literature survey revealed that benzoimidazole

derivatives are associated with potent biological activities such as insecticidal, pesticidal, herbicidal,

fungicidal, antibacterial etc. Furthermore, systemic variation of different aryl, alkyl or heterocyclic

moieties around the benzoimidazole nucleus markedly enhances the pesticidal activity. Various

scientists have synthesized different substitiuted derivatives of benzoimidazole and reported promising

pesticidal activities which are summarised below:

Kuarm et al. (2011) have been prepared 3-benzoimidazo-and 3-(benzothiadia-zoleimidazo-(1,2-

C)quinazolin-5-yl)-2H-chromene-2-ones as potent antimicrobial agents.

R1=Substituted aryl group; R2=4-OCH3, 4-Cl, 2-Cl etc.

New series of benzoimidazoles have been prepared and evaluated for their antimicrobial activity. Some

of them show promising antimicrobial activity Hasan et al. (2010).

N

N

N

O

RX

R

R=CH3 X=O; R=C2H5; X=S

Synthesis and evaluation of in vitro antimicrobial and antitubercular activity of 2-styryl

benzoimidazoles have been synthesized by Ramya et al. (2009).

24

R=NO2, Br, R1 =H, 3,4 (OCH3), 4-CH3, 3-OH etc.

Physico Chemical properties and antimicrobial activity of some new benzoimidazole derivatives have

been prepared Ansari et al. (2009).

R=H, C6H5, R1= 2-OH, 2-OCH3, 2-Cl, etc.

Synthesis and in vitro study of noval isooxazolylbenzoimidazolyl benzamides acrylamides and

propionamides as antimicrobial agents have been synthesized by Rajanarendar et al. (2008).

R=H, Halo etc., R1=H, 2-CH3, 2-Cl, R2=alkyl group.

Krunal et al. (2006) have been prepared 2-mercaptobenzoimidazole into -lactum segment derivatives

containing-cont – bridge with benzoimidazole.

R=m-CH3, p-CH3, m-OCH3, p-OCH3 etc.

Synthesis and potent antimicrobial activity of some new novel methyl or ethyl 1H-benzoimidazole-5-

carboxylates derivatives have been synthsized by Ozden et al (2005).

Vyas et al. (1997) prepared o-(phenyl)/o-(4-nitrophenyl)/o-(benzoimidazol-2-ylalkyl) phosphorothioate

derivatives. Their insecticidal activity was evaluated against periplaneta americana. (Indian cockroach),

and were found to be quite active against it.

25

R = H, Me; R1 = N, NO2, R2=alkyl, phenyl etc.

Synthesis and pesticidal activities of some fused benzoimidazoles have been given by Lutz et al.

(1996).

NQ

NRZ

X

R = cyano, COR1 etc; R1 = alkyl, alkenyl etc; Q = SOR3, COR4 etc; R3, R6 = alkyl, alkoxy etc; X = H, halo; Z = (halo - substituted)

Winfried et al. (1994) have prepared substitutedbenzoimidazoles which were reported as potential

pesticidal agents.

X1, X2, X3, X4 = H halogen, cyano etc; R1 = H, alkyl or substituted aryl; R2 = OH, cyano, alkyl etc.

Preparation of N-[(bromodifluoromethoxy)benzyl]benzoimidazole derivatives was given by Hiroshi et

al. (1991). These derivatives were useful for controlling (drug-resistant) insects and acaricides. Some

of them at 500 ppm concentration showed 100% insecticidal effect on Diabrotica undecimpunctata.

R1,R2,R3 = H, C1-4alkyl; R4 = halo, C1-6 (halo) alkyl etc; n = 0-4;

n = 2-4C(R4)nC.

26

Hirosi et al. (1990) synthesized some benzoimidazole congeners as insecticides and acaricides. These

compounds gave complete control of Plutella xylostella at 500 ppm.

R1 = H, halo etc; R2 = H, alkyl etc; R3 = H, alkyl; R4 = alkyl, haloalkyl; R5 = H, halo, alkyl; X = O, methylene etc; n = 1-4.

Preparation, of 2-polyfluoroalkyl (halo) benzoimidazoles as an insecticidal and acaricidal activities has

been reported by Yasuo et al. (1990).

R = halo; X = H, F; m = 3 - 9; n = 1 - 4.

Zdzislaw et al. (1989) have synthesized 2-arylbenzoimidazoles. Some of these were found to be useful

pesticidal and pharmaceuticals

R1 = H, alkyl; R2 = H, SO2; CH3-n Cln where n = 1-3; R3 = H, OH etc.

Benzoimidazole analogues were prepared by Weston et al. (1988) and were also screened for pesticidal

activities. In few compounds the mortality of Musca domestica was observed at 200 ppm.

R = H, C1-4 alkyl; R1 = Cl, (un)substituted Me; R2,R3,R4,R5, = H, Br etc;

E = C6-10 alkyl, -aralkyl etc.

Preparation and pharmacological screening of benzoimidazoles have been reported by Hiroshi et al.

(1987). These compounds have shown marked insecticidal and acaricidal activities.

27

R1 = H, lower alkyl; R2,R3 = H, halo etc. X = O, S, CH2 etc.

28

Following benzoimidazole congener as potential antibacterial agent has been prepared by Nandi and

Ray (1986).

2-(,-Difluoroalkyl)benzoimidazoles and benzoimidazolines have been synthesized by Boisvenue

(1984). These compounds were found to be useful for eradicating colonial insects such as ants and

termites.

R1 = halo, CF3 etc; R2 = H, COOR3; R3 = C1-8 alkyl, C3-4 alkenyl etc;

R4 = metal or onium; R5 = H, halo etc; R6 = Br, Cl or CF3; R7 = H or C1-4 alkyl; R8 = H, F etc.

Reingard et al. (1982) synthesized hexahydro-s-triazino[1,2-]benzoimidazoles which were

investigated as plant growth regulators, plant sex-expression modifiers and systemic insecticides.

N

N

NR

NCO2Me

R = C1-12 alkyl, ph etc.

Synthesis and pharmacological evaluation of 5-(3-substitutedphenoxymethyl-4-aryl/cyclohexyl-4H-

1,2,4-triazole-5-yl)-2-mercaptomethylbenzoimidazoles has been carried out by Gupta and Mishra

(1981). All the new compounds were screened for insecticidal activity and were found to possess

significant activity against male and female cockroaches.

29

R1 = 4 chlorophenyl, 2-ethyl phenyl etc.

Michael et al. (1973) have prepared polyhaloalkyl-benzoimidazole derivatives. These compounds

showed efficient pesticidal activity.

R = CF3, C2F5, etc; R1 = H, alkyl, acyl etc; X = Br, Cl; n = 3, 4.

Benzoimidazole derivatives have been synthesized by Gerhard et al. (1972). Several of these

compounds were proved as effective pesticides against Erysiphe graminis, E. cichora-cearum,

Cladosporium fulvum and Septoria apii.

R = halo or alkyl substituted phenyl

Pesticidal and herbicidal properties were reported in benzoimidazole derivatives by Fisons Ltd. (1971).

R=2-CH3, 2-OH, 2-NO2; R1 = 4, 6-Cl2 = Ph; X = CF3 etc

Stefan and Otto (1969) have prepared benzoimidazole analogues which were found to be useful as

herbicidal, fungicidal or ovicidal agents.

X = NHMe; R = R1 = R2 = H etc.

Glycoside derivatives of benzoimidazoles have been synthesized and reported as pesticidal and

antiviral agents by Chimetron (1968).

30

R = H, alkyl etc; R1 = furanosyl, pyranosyl etc; n = 0 – 3; R2 = a 5-membered

heterocycle having 1-S & 1 or more N atoms bound via its C atoms.

Reaction of 2-benzoimidazolinethione with dimethylsulfoxide and acetyl chloride have been prepared

and reported as pesticidal agent by Anzai and Suzuki (1967).

R1 = H; R2 = CH3 etc.

31

BENZOTHIAZOLE DERIVATIVES In the past years, the literature is enriched with progressive findings about the synthesis and

pharmacological action of fused heterocycles. The benzothiazole moiety is associated with wide

spectrum of pharmacological activities such as insecticidal, fungicidal, antibacterial etc. In light of

these interesting biological properties, a large number of benzothiazole derivatives have been

synthesized by several scientists and some of these are shown below:

Soni et al. (2010) have been prepared A novel series of 5-[2-(1,3-benzothiazol-2-yl- amino)ethyl-4-

(arylideneamino)-3-mercapto]-(4H)-1,2,4-triazoles were synthesized and evaluated for their

antimicrobial activity.

R=H, 4-OH, 2-NO2, 3-NO2, 2-Cl, 4-N(CH3)2, 3,4-OCH3 etc.

Synthesis of pharmaceutically important 1,3,4-thiadiazole and imidazolinone derivatives as

antimicrobials have been prepared by Mohd. Amir et al.(2009).

R=Phenyl, 4-Chlorophenyl, 2,4-dichlorophenyl,

4-Nitrophenyl, 2-aminophenyl etc.

The structure activity relationship (SAR) and antifungal activities of a series of novel 2-

aminobenzothiazoles are presented by Yamazaki et al. (2005).

X = –(CH2)2NHCO–, –(CH2)3NHCO–etc; R = H, NH2, NHCH2Ph etc.

Effective fungicidal activity was found in thiadiazolo and imidazobenzothiazoles derived from 2-

aminobenzothiazoles by Yoo et al. (1997).

32

R = H, Me, Cl etc; R1 = H, Me etc; R2 = H, Me etc.

Klaus et al. (1994) have prepared (thiocyanatomethylthio)benzothiazoles exhibiting useful pesticidal

activity. The following compounds kill 100 % of Blatella germanica at 1000 ppm concentration.

n = 0 -2; X = halo etc.

Nematocidal, insecticidal, acaricidal and fungicidal properties were reported in benzoxazole and

benzothiazole derivatives by Steven and Michael. (1994). These derivatives showed 80-100% mortality

against Spider mite, Green peach aphid, lesser against armyworm-larva and banded cucumber Beetle

larva.

X = O, S; n = 0 - 2; R1 - R4 = H, alkyl, alkenyl etc.

Acyl derivatives of 4-chloro-2-aminobenzothiazoles have been synthesized and tested for herbicidal,

insecticidal and fungicidal activities by Lacova et al. (1991).

R = Ac, Br etc;

A new compound, 6-maleimido-2-propylthiobenzothiazole as bactericide, fungicides and protozoacides

was prepared by Eva et al. (1991).

33

3-(Haloalkyl)benzisothiazoles as pesticides, were prepared by Dieter et al. (1990). These compounds

gave 100% control of Meloidogyne incognita.

R = H, haloalkyl etc; R1 = H, halo, NO2 etc.

Jinfang and Mingzhe et al. (1988) have synthesized some 2-substituted aminobenzothiazoles showing

mild insecticidal activity against the housefly.

R = 4-FC6H4, PhCH2 etc.

Dash et al. (1980) synthesized a series of benzothiazole derivatives. These compounds were evaluated

for antifungal and anticancer activities.

R1 = H, CH3Cl etc; R2 = R3 = R4 = H, Br etc.

34

Synthesis of some biologically active 2-aminobenzothiazole derivatives has been given by El-Naggar et

al. (1980). Several compounds were found to be acive against a number of microorganisms.

R = Tos – Gly; Tos – L–Ala etc.

35

PYRIDINE DERIVATIVES During the past decades, inspired by the remarkable success of novel insecticides belonging to the

group generally known as neonicotinoids e.g imidacloprid, acetamiprid. A number of research groups

focussed their attention on the synthesis of 2-, 5- or 2- & 5-substitutedpyridine derivatives and reported

remarkable biological activities viz. insecticidal, herbicidal, fungicidal etc., some of these are

summarised below:

Synthesis and antifungal activity of 5,6,7,8-tetrahydroimidazo [1,2-a] pyridine derivatives have been

prepared by Ozdemir et al. (2010).

R1 = alkyl group; R2 = H, Phenyl Group etc.

Gangadasu et al. (2009) have been prepared of 2-chloro-5-methyl pyridine-3-alefin derivatives.

X=COOMe, CN, CH2OH, COMe, CH2OAc etc.

Synthesis and pharmacological study of thiazolidinones and mannich base of 4-amino-3-mercapto-5-

pyridin-3'-yl-[1,2,4]-triazole by Dave et al. (2007)

R= Substituted aryl group.

2-Chloro-5-(5-aryl-1,3,4-oxadiazol-2-yl)methylpyridines have been prepared by Holla et al. (2004).

These derivatives were evaluated for insecticidal activity, and observations were recorded for mortality

of insects.

36

R = -H, - Cl etc.

Synthesis of some diimidazolin-5-onecarboxamide derivatives of 1,4-dihydropyridine as possible

antifungals and insecticidals, has been reported by Raj and Rao (2003).

R = Ph; 4-methoxyphenyl etc.

Kagabu et al. (2002) have reported good insecticidal and neuroblocking activities in thiacloprid and its

acyclic analogues.

R1 = H, Me; R2 = NHMe, NHEt etc.

Insecticidal and binding activities of N3-alkylated analogues of the chloronicotinyl compounds have

been given by Nishiwaki et al. (2001).

Y = N, CH; R = H, CH3, C2H5 etc.

Wakfield (2000) has prepared 2-haloalkylthiothiazolo[4,5-b]-pyridine derivatives which have been

used for controlling helminths, nematode, insect, acarid pests and parasites.

R = halo, NO2 etc; n = 0 - 3; Q = alkenyl, haloalkenyl etc.

5-Amino-7-aryl-6-cyano-3-substituted-thiazolo[4,5-b]-2,3,4,7-tetrahydropyridine-2-thiones and 7-aryl-

6-cyano-3-substituted-2-thioxathiazolo[4,5-b]-2,3,4,5,6,7-hexa-hydropyridin-5-ones have been

37

synthesized and screened for their insecticidal activity against S. litura and T. urticeae. Khan et al.

(1998). These compounds displayed activity ranging from 21% to 80%.

R = C6H5, 2-CH3C6H4 etc; R1 = 4-OCH3, 4-Cl, 4-F etc.

Nobuo et al. (1997) reported pesticidal activity in acylaminopyridines.

R1 = halo, alkyl etc; R2 = alkenyl, alkynl etc. R4 = halo cyano etc; R5 R6 = H, alkyl; Q = N, methine ; m = 0, 1; n, r = 1,2

Pesticidal, insecticidal, fungicidal, acaricidal and nematocidal activities have been exhibited in

substituted 4-(carbonylamino)-pyridine congeners (Harald et al., 1996).

A = H, alkyl etc; R1 = (un) substituted alkenyl etc; R2 = H, etc; R3, R4 = H, halogen etc; Z = (un) substituted aryl, cycloalkyl etc.

Synthesis of some pyridyl analogues has been given by Knueppel et al. (1995). These pyridine

derivaties were found to possess prominent pesticidal activity.

NNMeACO2MeCArC

Ar = (substituted) phenyl or pyridyl; A = H2C, MeOCH : C

Tabuchi et al. (1994) synthesized a series of acyclic nitroethene compounds containing (6-substituted)-

3-pyridylamino group. Out of these compounds, compound 1-[N-(6-chloro-3-pyridyl)-N-

methyl]amino-1-(N-formyl-N-methyl)amino-2-nitro-ethene exhibited potent insecticidal activity.

38

Moriya et al. (1993) have modified the structure of imidacloprid by introducing five membered

heteroaromatic rings. These synthesized compounds possessed insecticidal activity.

Ar =

etc.

X=halo group.

Reddy et al. (1991) prepared a new series of bis (2-pyrazolin-3-yl) benzenes and pyridines which

presented remarkable fungicidal and insecticidal activites.

R = H, 4 - CH3 etc; X - CH, N etc.

Pyridine derivatives as pesticides and acaricides, have been synthesized by Izuml et al. (1990).

X = halo, alkoxy etc; R1, R2 = H, halo etc.

Yuzuru et al. (1989) synthesized 7-trifluromethyl[1,2,4]triazolo[3,2-b]thiazolo [4,5-bi]pyridine. This

compound showed excellent insecticidal activity at low concentrations against housefly, german

cockroach and plant hopper.

Synthesis of 2-(aminomethyl) pyridines as potential pesticidal agents, has been illustrated by Ivanov et

al.(1989).

R1 = H, Me; R2 = H, Ph etc; R3 = Et, Me; R4 = Et, etc.

39

Efficacious insecticidal, herbicidal & fungicidal activities have been found to be associated with

substituted (dichloromethyl) pyridines by (Orvik 1988).

R2, R4, R6, = CHCl2; R3R5,= Br, CF3, cyano etc.

2-Phenoxy-5-trifluoromethylpyridine derivatives were prepared and found to be useful insecticidal and

herbicidal agents (Ryuzo et al., 1987).

X = H, Cl; Y1, Y5 = H, Halo etc; Y2,Y4 = H, OH etc; Y3 = H, cyano, NO2 etc.

Hans et al. (1986) synthesized trifluoromethylpyridinylphosphates possessing pesticidal property.

X = O, S; Y = O, NR where R = H, alkyl; R1,R2 = alkyl

Following pyridine congeners exhibiting prominent insecticidal, acaricidal and nematocidal activities

have been reported by Koichi et al. (1985).

X = S, O; R = Et, Me, etc.

Insecticidal property was observed in benzoyl urea and pyridine nucleus (Ishihara Sangyo Kaisha Ltd.,

1983).

R = F, Cl, Br etc; R1 = F, H; R2 = 2-Chloro-3-trifluoromethyl 6-pyridyl; Pyridine derivative was found to be effective insecticide against jassid (Amrasca devastans) and pink

bollworm (Pectinophoro gossypiella) in cotton by Agarwal and Katiyar (1975).

40

Synthesis and pesticidal activities in various phosphates of substituted pyridyl compounds have been

given by Aries (1973).

X = O, S; R = F; R1 = Et, Me.

In (1972), Domenico gave the synthesis of several thio-sulfinyl and sulfonyl containing pyridine

compounds which were found to be effective insecticidal and pesticidal agents at concentrations of 10-

500 ppm.

QR = 4 - SH; X = 3,5,6 - Cl3; Y = 2 - CN.

Howard (1971) prepared bis- and tris(thio-sulphinyl-, and sulphonyl)-pyridine analogues which showed

proficient pesticidal activity.

41

THIAZOLE DERIVATIVES

A large number of heterocyclic compounds have gained the medicinal importance in the recent years:

Among these, thiazole derivatives, exhibited various biological activities especially insecticidal,

antifungal, antibacerial etc. Furthermore, substitution pattern in thiazole nucleus at position 2 or 4 by

different heterocyclic moieties played an important role in delineating the biological properties.

Following thiazole derivatives have been prepared by various scientists proved that thiazoles possessed

good pesticidal activity:

Lidia S. Konstantinova et al. (2009) have been synthesized of 5-phenylimino, 5-thieno or 5-oxo-1,2,3-

dithiazoles and evaluation of their antimicrobial and antitumor activity.

R=Cl, Br, NO2; X = PhN, S, O etc.

Synthesis and antimicrobial activity of 2-(2'-arylidene-hydrazino-acetyl-amino)-4-phenyl-1,3-thiazoles

and 2-[2'-{4"-substituted-aryl-3"-chloro-2"-oxo-azetidine}-acetyl-amino]-4-phenyl-1,3-thiazoles by

Sonwane et al. (2008).

Ar = H, CH3, OCH3

Synthesis of some new 2-(4-alkylthiophenoxy)-4-substituted-1,3-thiazoles as possible anti-

inflammatory and antimicrobial agents by Karabasanagouda et al. (2008).

Ar=H, Phenyl, R2=CH3, C2H5 etc.

Preparation of thiazole congeners has been given by Tomio (2004). Some of these derivatives

possessed pesticidal activities.

42

R = alkyl, Ph etc; R1, R2 = alkyl, Ph etc.

Katsutoshi et al. (2002) have prepared 4-(1-fluoroethyl) thiazole-5-carboxamides, their intermediates

exhibiting promising pesticidal activity.

R1 = (un)substituted Ph, (un) substituted PhO, etc;

Ar = bond, linear or branched C1-6 alkylene.

Synthesis of thiazoles as pesticidal agents, has been given by Thomas et al. (2002).

Q = CH, N; Y = NO2, CN etc; Z = CHR3, O etc;

R1, R2 = An alkylene bridge having two or three C atoms.

2,2'-Phenylenebis[5-(substitutedphenyl)methylenethiazolo[3,2-b]-1,2,4]triazol-6(5H)ones have been

synthesized by Dubey et al. (1994). Several of these compounds exhibited promising, in vitro, growth

inhibitory activity against the tested phytopathogenic fungi.

R = H, 2,4-(OMe)2 etc.

Chlorothiazole congeners were prepared by Hideki et al. (1991). Some of these derivatives displayed

pronounced insecticidal activity.

43

R = Cl, NH2 etc.

Lutomski (1990) synthesized a novel series of 5-(thien-2-yl)-2-phenylthiazoles as photoactive

insecticides, acaricides & nematodes.

R1 = (halo) alkoxy carbonyl, haloalkyl etc;

R2 = haloalkyl (thio) PhS, NO2 etc.

Aldo et al. (1989) prepared imidazo[2,1-b]thiazolecarbamates possessing potent insecticidal activity.

X-X1 = CH : CH, MeC: CH etc; R = Cl, 4-Cl C6H4, Me.

Synthesis and phototoxicity of some 2-(phenyl-or-2-or 3-thienyl)-4-substituted-thiazoles revealed

useful insecticidal activity (Singh and Sehgal., 1988).

R = 2-thienyl, Ph etc; R1 = 2-thienyl, substituted Ph etc.

4-(Alkane-sulfonyloxy)thiazoles were synthesized by Shizuo et al. (1987). These compounds at 200

ppm gave 100% kill of organophosphate and carbamate resistant Nephotettix cincticeps.

R1 = (halo) alkyl; alkenyl etc; R2 = (halo) alkyl; R3 = (halo) alkyl, Br Cl; x = 0-2

Jozef (1983) synthesized 3-amidinobenzisothiazole-1,1-dioxides as useful pesticidal agents and some

of these gave 70-100% kill of Aphis cracivora.

44

R = H, Halo etc; R1 = H, Me; R2 = (CH2)3; R3 = alkyl, alkenyl.

Synthesis of 2,3,8,9-tetrasubstituteddimidazo[2',3'-b:2", 3"-b"]benzo[1,2-d:4,5-d'] bis- thiazolo-5,11-

diones as possible pesticides, has been reported by Soni and Saxena (1981).

R, R1 = H, CH3, C6H5.

Some new 2-(o-mercaptophenyl) amino-4-substituted-thiazoles and oxazoles were prepared by Nath et

al. (1979). These compounds have been assayed for their pesticidal activity and the results were quite

promising.

R1 = CH3-, C6H5-etc; R2 = H, Cl, Br; X = S, O.

Rao and Mitra (1977) prepared some 2,4 disubstitutedthiazoles as promising fungicidal agents.

R = Phenyl, p-anisyl.

Robert (1973), reported prominent pesticidal activity in phosphates, thiophosphates, dithiophosphates

of 5-nitro or 5-bromo diversly substituted thiazoles.

R = Cl, Me; X = O, S.

45

Taichiro et al. (1973) synthesized N-(3,5-dichlorophenyl)-4,5-dichloroisothiazol-3-one. This

compound was tested for prevention of Rice blight and S. Orientalis infestation of Sesamun indicum

and found to be good pesticidal agent. The LD95 value for S. orientalis sports was 1 g/mL.

46

Some new 3-chloro-4-cyano-5-(acylamino) isothiazole derivatives were investigated for their pesticidal

and herbicidal activites (Alfred et al., 1971).

R = C1-10 alkyl, C3-7 cycloalkyl; X = alkali, alkaline earth.

Synthesis of many thiazolylphenylphosphates as pesticides, has been given by Bernard (1970). These

thiazole moieties were found to kill several species of insects and mites in concentrations from 0.4 ppm

to 1%.

[IaQ = P(2) (OR3)2], [(Ib, Q = H.HX)]; R1 = Me; R2 = H; X = Cl.

47

PYRAZOLE AND PYRAZOLINE CONGENERS

Heterocyclic compounds particularly five or six-membered have occupied the first place among various

organic compounds for their diverse biological activities. Pyrazole and pyrazolines are the most

important representatives of hydrazine in both the synthetic and theoretical respect. Compounds of

these classes exhibited diverse kinds of properties like insecticidal, herbicidal, antifungal, anti-

inflammatory etc. Furthermore, in the light of these observations, scientists have prepared several

pyrazole and pyrazoline congeners possessing pesticidal activities and some of them are given below:

Gautam et al. (2010) have been prepared some new cinnoline based chalcones and cinnolinc based

pyrazoline derivatives.

NN

C

CH3

NNH

CH

CH2 R

R=3-NO2, 2-Cl, 3-Cl, 4-Cl, 3-Br, 2-NO2 etc.

Synthesis and antimicrobial evaluation of 1-(benzofuran-2-yl)-4-nitro-3-arylbutan-1-ones and 3-

(benzofuran-2-yl)-4,5-dihydro-5-aryl-1-[4-(aryl)-1,3-thiazol-2-yl]-1H-pyrazoles by Bakr et al. (2009).

Masao et al. (2004) synthesized pyrazole derivatives as intermedicates in the production of herbicidal

isoxazoline derivatives.

R1 = C1-6 alkyl, R2 = C1-3 haloalkyl; R3 = hydrogen, (un) substituted C1-3 alkyl

R4 = hydrogen or C1-3 haloalkyl etc.

3-Substituted-N-acetyl-N-[4-(4-cyanophenoxy)benzyl]-1-methylpyrazole-5-carboxamides as an

insecticidal agents against Spodoptera litura were prepared by Shiga et. al (2003).

48

R1 = methyl, ethyl etc.

1,3,5-Trisubstitutedpyrazoline derivatives have been synthesized by Raj and Rao (2003). Some

pyrazoline congeners, screened for their insecticidal and antifungal activities, showed moderate

activities.

R = phenyl, 2, 4-dinitro phenyl etc and R1 = substituted aryls.

Insecticidal, herbicidal, acaricidal etc. activities were found in 3-(1-fluoroethyl)-1-methylpyrazole-4-

carboxamides. This study was done by Katsutoshi et al. (2002).

R = (un) substituted Ph, (un) substituted PhO; A = bond, C1-4 alkylene

McCann et al. (2001) reported indoxacarb: Oxadiazines as a new class of pyrazoline type insecticides.

R = 4-F-Ph, 4-Cl-Ph, Me etc; Z = OCF3, CF3 etc; X = Cl, Br, H etc.

N-alkylpyrazolines have been synthesized by Nishimura et al. (1999). These derivatives exhibited good

insecticidal activity against americana periplaneta and houseflies.

R = H, CH3, C2H5 etc.

Otto et al. (1998) synthesized various 3-(4-cyanophenyl)pyrazoles as herbicidal agents.

49

R = ZR2, R1,R2 = H, alkenyl etc; R3, R4 = H, halo etc;

R5 = H, halo etc.

Finkelstein and Strock (1997) have designed and synthesized novel pyrazole-methanesulfonates with

the help of new model. The new compounds demonstrated very high level of insecticidal activity with

low level of acute mammalian toxicity.

R1 = CON (CH3)2, SO2CH3, SO2C3H7 etc; R2 = H, 5-NH2, 4-Br, 5-CH3 etc.

Prominent insecticidal and anti-acetylcholinestearase activities were found in a novel series of 3-

methanesulfonyloxy-2-pyrazolines by George et al. (1996).

R1 = Me, Ph etc; R2 = Me, H; X = CONH2, CONH Ph etc.

Andreas et al. (1996) have synthesized 1-[(4-isopropoxy phenyl)] carbomyl-pyrazolines. These

compounds were evaluated for pesticidal activity and found to exhibit useful activity against Heliothis

virescens.

X = alkoxy, haloalkoxy; Y = F, Cl etc.

3-Phenylpyrazoline derivatives were found to possess advantageous insecticidal activity (Rainer et al.,

1996).

R1 = (un) satd, (un) substituted etc; R2 = H, (un) substituted alkyl;

X=CH3, H; Y = OCH3, OC2H5; Z=NO2; R3=C2H5; R4=Phenyl group; R5=Alkyl group; R6=Alkene group etc.

50

Methyl-3-(4-chlorophenyl)-4-methyl-1-[N-(4-substitutedphenyl)carbomoyl]-2-pyrazoline-4-

carboxylates and related compounds were prepared, and their insecticidal activity was determined

against american cockroaches, periplaneta americana. The findings indicated that the greater the

hydrophobicity and the more electron-withdrawing property of the substituents, the higher were the

activity. (Hasan et al.,1994).

Z = S, O; X = H, 4-Cl, 3-F, 4-CH3 etc.

Preparation of following pyrazole congener as herbicide was given by Heistracher et al. (1992). At 0.25

kg/la postemergent gave very good control of broadleaf weeds and was well tolerated by wheat.

Remarkable insecticidal, bacteriocidal and fungicidal properties of some bis-(2-pyrazolin-3-yl)

benzenes and pyridines have been reported by Reddy et al. (1991).

R = H, 4-CH3 etc; X = CH, N etc.

Itaru et al. (1990) gave the synthesis of [(5-pyrazolcarboxamido) alkyl] pyridine derivatives as potent

insecticides, miticides and fungicides. These compounds at a concentration of 500 ppm showed 100%

miticidal activity.

R1 = C1-4, alkyl etc; R2, R3= H, C1-4, alkyl etc; R4 = H, halo etc;

X = halo, H etc; m = 1-3.

51

Substituted 1-arylpyrazoles their preparatian and their use as pesticides, especially as insecticides, have

been given by Jensen-Korte et al. (1989).

R1 = H, halo alkyl etc; R2 = halo, cycloalkyl etc; R3 = cyano, COYR4 etc; n = 0, 1, 2; Ar = substituted Ph etc.

Some 1-carbamoyl-4-phenylpyrazoline derivatives were synthesized by Shimigo et al. (1987). These

derivatives elicited good insecticidal agents.

R = alkyl; R1 = halo, alkyl; R2 = CONHR3

Effective pesticidal, fungicidal and herbicidal activities were found in pyrazolylsulfonyl ureas. (Nissan

Chemical Industries ltd., 1986).

R = H, Ph etc; R1, R2 = H, alkyl etc; R3, R4 = H, alkyl etc; X = N : CR5

Certain pyrazole congeners have been prepared and some of these showed promising herbicidal activity

(Nihom Nohyaku Co. Ltd., 1985).

R = H, halogen, etc; Z = O, S etc.

52

Several new 4-(1,5-disubstituted-2-oxoindolinylideneimino)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-

ones have been synthesized, and evaluated for their insecticidal activity against male and female adult

cockroaches by micrometer syringe method. (Gupta and Gupta, 1982).

R = H, Br, CH3; X = H, CH3, Cl.

Grosscurt et al. (1979) have prepared 3,4-diphenylcarbomoyl-2-pyrazolines, which were found to

exhibit much higher insecticidal activity. The insecticidal properties were evaluated with the larval

stages of Aedes aegypti L., Pieres brassicae L., and Leptinotarasa decemlineata say.

RX = H, 4-F, 4-Cl etc; Ry = H, 4-NO2, 4-Cl etc; Rz = H, 4-Cl etc.

53

QUINAZOLINONES

Synthesis of 4-(3H)-quinazolinones by microwave assisted tandem reaction and evaluation of their

antibacterial and anti fungal activities by Priya et al. (2011).

R1=C6H5, 2-ClC6H4, 2-BrC6H4 etc.

Synthesis and characterization of new quinazolines as potential antimicrobial agents by Desai et al.

(2007)

R = 2-chlorophenyl; Ar = different aryl groups

Synthesis of 3-aminoquinazolinone derivatives was given by Masahiro et al. (1999). These compounds

showed promising insecticidal activity.

X = H, alkyl, halo etc; R1 = H, CH3; R2 = alkyl, acyl etc;

R3 = H, OXO etc; Y = H, halogen etc; Z = O, S.

Significant antifungal and antibacterial activities have been found in 2-

(dialkylamino/piperidino/morpholinomethyl)-7-halo-thiazole[2,3-b]quinazolin-5-ones by Bennur et al.

(1997).

R = I; R1 = Morpholino, NEt2 etc.

Ghorab et al. (1996) synthesized a series of new 3-[4(3H)-quinazolinone-2-yl)thiomethyl]-1, 2,4-

triazole-5-thiols (III) and were determined for insecticidal activity against Chrysomyia albiceps. Few

of these compounds showed insecticidal activity equivalent to that of malathion.

54

X = Cl, I; Z1 = Cl, H; R = CH3, C2H5, C6H5, R1 = CH3, C2H5 etc.

In 1996, Masahiro et al. (1996) prepared substituted aminoquinazolinone or thione congeners and these

compounds exhibited useful pesticidal and insecticidal activites.

R = H, OH etc; X = halogen, OH etc; Y = O, S;

Z = N:CR2, N(R3)–CO etc; R1 = H, alkyl etc; n = 0 – 4.

Moderate antifungal activity was found in 6-(4'-substitutedbenzylidene-2'-methyl/phenyl-5'-

imidazolinon-1'-yl)-2-methyl-4-(3H)-quinazolinones (Singh et al., 1994).

R = 2-4-ClC6H4 etc; X = Me, Ph.

Biological activites viz antimicrobial, anticonvulsant, analgesic etc.of various quinazolinone

derivatives have been extensively studied by Buyuktimkin et al. (1992).

R = H, 4–CH3, 4-C2H5 etc.

Novel series of quinazolone derivatives were prepared and evaluated as potential antimicrobial agents

(Habib and Khalil 1984). Some derivatives possessed prominent antifungal and antibacterial activities.

R = nC4H9–, 4–CH3C6H4, C6H5, CH3 etc.

55

Synthesis of some new 2-[3-aryl(or cyclohexyl)-6-bromo(or 6,8-dibromo)-4-oxo-3H-quinazolin-2-

ylthio]-N-(4-arylthiazol-2-yl)acetamides has been described by Misra and Gupta (1982). These

compounds were screened for their insecticidal, antibacterial and anti- acetylcholinsterase activities;

most of them exhibited significant activities.

R1 = Benzyl, cyclohexyl etc; R2 = Phenyl, 4–chlorophenyl;

R3 = H, CH3; X = H, Br.

Some 2-phenyl-3-substitutedquinazolin-4(3H)-one derivatives have been synthesized by Gupta and

Chandra (1979). Some of these showed significant insecticidal activity.

X = 1, 2 etc; R = C6H5, CH3 etc.

TRIAZINE DERIVATIVES

Saleem et al. (2002) have reported the synthesis of dihydrotriazines possessing promising pesticidal

activities.

A = bond; X1 = R8; X2 = X3, X4 = H; R8, R1 = (un) substituted aryl, heteroaryl; R2 = H, OH etc; R3a, R3b = R3,R3 = (C:y)n WR9

Preparation of aminotriazines as pesticides was given by Ernst et al. (1997).

R = H, C1-6 alkyl

Following triazine derivatives possessing herbicidal property, have been synthesized by Toshihiro et al.

(1992).

56

A = Q, Q1; R = H, Me; X = F, Cl.

Synthesis and pesticidal activities of some substituted triazine derivatives have been given by Gupta et

al. (1985).

R = OCH3, H, Cl etc.

Insecticidal and acaricidal activities were found in the following two triazine congeners by Verena et

al. (1982).

R = cyclopropyl or R = IsoPr.

Brechbuhler et al. (1981) have prepared 2-cyclopropylamino-6-diamino-s-triazine and this compound

exhibited good activity against Musca domestica, Aedes aegypti, and Lucilia sericata larva.

[1]-Benzothieno[3,2-d]-v-triazines have been synthesized by Joseph (1977). These compounds are

useful as bactericides, fungicides, protozoacides and algicides.

R = Cl, MeO etc; R1 = H, Cl, NO2

Federova et al. (1973) synthesized the following triazine derivative which was found to possess

promising insecticidal activity.

Dovlatyn et al. (1971) prepared 2-(methylthio)-4-[alkyl(dialkyl)amino]-6-[-hydroxy (methoxy)-

-trichloroethyl]-amino-s-triazines. These compounds exhibited pesticidal activities.

57

R = H; R1 = (CNH2) : NH.HCl; R2 = NHEt, NHMe etc.

58

THIAZOLIDINONE CONGENERS

Synthesis, configurational analysis and antimicrobial activity of imidazolidinone, thiazolidinone and

isoxazolone derivatives of 9,10-phenanthrehequinone by Arora et al (2011).

X=NH, NMe, S; Y=O, S.

Pushpak et al. (2011) have been synthesized some new 4-thiazolidinone derivatives as biologically

potent agents.

R1=H, CH3, OCH3; R2=H, CH3, OCH3, Cl; R3=H, CH3 etc.

Synthesis and pharmacology study of thiazolidinones and mannich bases of 4-amino-3mercapto-5-

pyridine-3'-yl-[1,2,4]-triazole by Dave et al. (2007).

R=H, CH3; R1 = OCH3, Cl; R2 = Phenyl.

Substituted 5-methyl-2-methyl/phenylimino-3-(3-methyl-5-styryl-isoxazol-4-yl)-thiazolidin-4-ones

have been synthesized and screened for antimicrobial activity. (Rajanarendar et al. 2004).

R = CH3, C6H5; Ar = C6H5, C6H4– Cl (p) etc.

59

Govindrajan et al. (2003) has prepared following thiazolidinone compound which exhibited

antibacterial and antitubercular activities.

Various thiazolidine derivatives were prepared by Xu and Qian (2004). These compounds were tested

against insect and some of these showed moderate insecticidal activity.

R1 = H, Me; R2 = H, Cl etc; R3 = H, Me etc; R4 = CH2OH etc;

R5 = CH2OH, Et etc.

Parmar et al. (1999) have prepared 6-p-anisyl-5-cyano-3-N-methyl-2-(2'-aryl-5'H-4'-thiazolidinon-3'-

ylamino)-3,4-dihydropyrimidin-4-ones and evaluated for antimicrobial activity. Few of these

compounds exhibited comparable activity with standard drugs ampicillin and chloroamphenicol against

E. coli.

R = C6H5-, 2-Cl-C6H4-, 2,4-(Cl)2C6H3- etc.

Synthesis of 5-tert-butyl-carbamoyloxy-3-(3-trifluoromethyl) phenyl-4-thiazolidinone as herbicidal

agent has been discribed by Sharples et al. (1998).

N

S

OHN

O

Me

MeMe

F3C

O

60

Orlinskii et al. (1995) synthesized a series of uncondensed 2-thiazolidones with polymethylene and

arylene bridges. These compounds were screened for pesticidal activity.

Y = H2, X etc; n = 2, 4, 6

Preparation of the following 4-thiazolidinone derivative and evaluation for insecticidal and fungicidal

activities have been reported by Cesur. (1987). This compound showed activity against Wine downy

mildew.

Insecticidal activity of oxazolidinone and thiazolidinone derivatives was evaluated by Nissan Chemical

Industries Ltd. (1985).

Z = O, S; R = cycloalkyl, alkyl, etc; R1 = H, Me, 2-Cl etc.

Themistocles and Silva (1977) synthesized 2-(carbamoyloximino)-4-thiazolidinone compounds which

were found to be good insecticidal, miticidal or nematocidal agents. These compounds are pesticidal

with low phytotoxicity.

R = H, Et etc; R1 = H, Me etc; R2 = H, Me, Et etc; R3 = H, Me, etc; R4 = H, Me.

3-Substituted-2-adamantyl-4-thiazolidinones have been synhesized. All these compounds inhibit the

growth of gramnegative and grampositive bacteria and fungi. (Fenech et al., 1979)

61

S

N

O

C10H15 R

R=

etc.

Several thiooxathiazolidinone derivatives have been synthesized and their herbicidal activity has also

been reported by Tetsu et al. (1976).

R1, R2 = halo lower alkyl; X = halogen; n = 1-3 etc.

62

Substituted 2-thio-4-thiazolidinones and 2,4-thiazolidinediones were prepared by Tong et al. (1975).

These derivatives exhibited promising insecticidal activity.

R=OCH3, Cl; R1 = alkyl or aralkyl; X = O or S.

Some carbamoyloxyaminothiazolidinone and oxazolidinone congeners have been synthesized by

Punga (1973). These derivatives showed fungicidal, insecticidal and acaricidal activites.

S

NR2O

NO2CNR3R4R

R1

R – R3 = alkyl; R4 = H, Me etc.

63

AZETIDINONE DERIVATIVES

Baviskar et al. (2011) have been prepared of thiazolyl triazole substituted azetidinone as antimicrobial

agents.

R =H, C6H5, CH3.

Synthesis and antimicrobial screening of 4-aryl 3-chloro-1-(5-nitroindarol-1-yl) acetamido-2-oxo-

azetidines by Upadhyay (2011).

Ar= substituted aryl group.

Synthesis and evaluation of some new benzoimidazol derivatives as potential antimicrobial agents by

Ansari et al. (2009).

Sukla et al. (2008) have been prepared of some new 5-[2-{(1,2,3-benzotriazole)-1-yl- methyl}]-1'-(4'-

substituted aryl-3'-chloro-2'-oxo azetidine)-amino-1,3,4-thizdiazoles : Antifungal and antibacterial

agents.

Ar=C6H5, CH3.

Formation and antimicrobial activity of 2-azetidinones from selective ester cleavage in 1,3,3-

trisubstituted 4-[2'-(O-diarylacyl)-hydroxyphenyl]-2-azetidinones by Singh et al. (2008)

64

R=OCH3 Cl, Br; R1 = C2H5, CH3.

N9-[hydrazinoacetyl-(2-oxo-3-chloro-4-substituted aryl azetidine)]-carbazoles as Antifungal and

antibacterial studies by Srivastava et al. (2008)

Ar=H, C6H5, CH3.

1-[5'-{2-Benzothiazolyl(thio)methyl}-1,3,4-thiadiazol-2'-yl]-4-substituted-3-chloro-2-oxoazetidines

have been synthesized by Srivastava et al. (2004) and tested for their antibacterial, antifungal and

anthelmintic activities. Some of these derivatives showed promising activities.

R1= CH3,H; R2 = Substituted aryls

4-Substitutedphenyl-3-chloro-1-[p-(1,8-naphthyridin-2-yl)phenyl]-2-azetidinones have been prepared

and screened for their antibacterial and antifungal activities by Mogilaiah et al. (1999).

Ar = C6H5, p-CH3-C6H4, O-Cl-C6H4, p-Cl-C6H4 etc.

Patel et al. (1999) have prepared some 2-azetidinone congeners and examined them for antimicrobial

and tuberculostatic activities. These compounds displayed moderate to good and comparable activity

with known standard drugs.

65

R = Phenyl, 2-chlorophenyl, 4-chlorophenyl etc.

Gajare et al. (1997) gave the synthesis of 3-chloro-4-substitutedaryl-2-azetidino-1-yl-3,5,6-tri-

chloro-2-pyridyloxyacetamido. Some of these compounds showed good herbicidal activity, while

remaining are found moderately active.

R = C6H5, 4-ClC6H4, 4-BrC6H4, 4-CH3C6H4 etc.

Franz (1972) gave the synthesis of 3,3-dialkyl-1-phenyl-2-azetidinones. These derivatives were found

to possess useful pesticidal activity.

N

R3

R2O

R1

R

R = H, Cl or MeO; R1 = H or NO2; R2, R3 = Me or Ph, (CH2)5 etc.

66

EXPERIMENTAL

All reagents and solvents were generally used as received from the commercial

supplier. Reactions were routinely performed in oven-dried glassware. Melting points

were determined with an electrothermal melting point apparatus, and are uncorrected.

The homogeneity of all newly synthesized compounds was checked by thin layer

chromatography (TLC) on silica gel-G coated plates. Eluent was a mixture of

different solvents in different proportions, and spots were visualized under iodine

chamber.

Elemental analysis (C, H, N) of all the compounds was performed on Carlo Erba-

1108 elemental analyzer, and results were found within the + 0.4% of theoretical

values.

Infrared (IR) spectra (KBr) were recorded on Brucker–IFS–66 FTIR instrument and

wave number () was recorded in cm-1.

1H-NMR spectra were recorded JEOL, GSX-400 FTNMR instrument at 400 MHz in

CDCl3 or DMSO-d6 unless otherwise specified, and chemical shifts () are reported in

ppm. relative to tetramethylsilane as an internal standard

Mass spectra were determined from Mass Finniganmat 8230 MS.

67

BIOLOGICAL STUDY

Various compounds of SCHEME–I, SCHEME II, SCHEME–III, SCHEME–IV and

SCHEME–V have been synthesized and evaluated for insecticidal activity against

male or female cockroaches (Periplaneta americana). These compounds were also

assayed in vitro for their antifungal and antibacterial activities.

Insecticidal Activity The insecticidal activity was determined by the method of Joshi and Tholia (1973).

The cockroaches of either sex were divided in groups having five cockroaches each.

An acetone solution (0.02 mL of 5 g/L) of standard insecticide, parathion, and

different test compounds were injected on the ventral side of the insect, between the

fourth and fifth abdominal segments with the help of a micrometer syringe. Insects

receiving 0.02 mL of acetone by the same route served as control.

The treated cockroaches were kept under observation to record the time taken until

100 % mortality. During this period, no food was given. In an other set of experiment,

most active compound of each SCHEME at two graded doses i.e. 0.2 ml of 10 g/L and

20 g/L were also injected to groups of insects with identical doses of parathion. The

statistical significance of the difference between the data of standard and test

compounds was calculated by employing student’s ‘t’ test (A 1).

Antifungal Activity

The standard agar disc diffusion method (Pai and Platt, 1995) was performed to

evaluate the antifungal property of test compounds and standard fluconazole.

Aspergillus fumigatus, Candida albicans ATCC 2091, Candida albicans ATCC

10231, Candida Krusei GO3 and Candida glabrata HO5 were used in this study. All

cultures were routinely maintained on SDA (A 2) and incubated at 30 ºC. In order to

prepare homogeneous suspensions of these fungi for disc assays, they were grown

overnight in sabouraud broth, centrifuged to collect the pellet and re-suspended in

sterile phosphate buffered saline. The fungal pellet was homogenized in a sterile

hand–held homogenizer. This suspension was then plated onto SDA using a bacterial

spreader to obtain an even growth field.

68

Sterile 6 mm Whatman filter paper discs (A 3) were impregnated with 250 g/mL

concentration of various test compounds and standard drug, fluconazole. These discs

were then placed in the centre of each quadrant of an SDA plate. Each plate had one

control disc impregnated with 10% DMSO in methanol. The plates were incubated at

30 ºC. After 48 hours, the plates were removed and the radius of the zone of inhibition

(in mm) was measured.

Antibacterial Activity

The antibacterial activity of test compounds and standard chloramphenicol was done

by filter paper disc method (Gould and Bowie, 1952) against Staphyloccous aureus

209 p and Eschericia coli ESS 2231, at a concentration of 250 g/mL. Media with

10% DMSO in methanol was set up as control. The presence of methanol caused no

visible change in the bacterial growth.

The Whatman filter paper discs of standard size (7 mm) were prepared. These discs

were put into 1 oz screw capped wide-mouthed containers. These bottles are then

sterilised in hot-air oven at 150 ºC. Solution is then added to each bottle. Before use,

the bottles should be shaken to distribute the discs around the walls of the container

and this allows them to be picked up more easily with the forceps.

The discs are transferred to the inoculated plates with a pair of fine pointed tweezers.

The tweezers may be kept with their tips immersed in 70 % alcohol, which is flamed

off before use to prevent contamination.

The test organisms were grown on nutrient agar (A 4) and, before use, were

subcultured in nutrient broth at 37 ºC for 18-20 hours. Each disc was applied carefully

to the surface of the agar without lateral movement once the surface had been

touched; where necessary they were flattened down with the points of the forceps.

The plates were then incubated for 24 hours at 37 ºC, and the resulting zones of

inhibition (in mm) were measured.