Presentation for viva

SYNTHESIS OF HETEROCYCLIC COMPOUNDS AND EVALUATION OF THEIR BIOLOGICAL ACTIVITIES

Mr. Abhishek R. JoshiC/O Dr. K S Parikh (Research Guide & Principal)

Chemistry Research LaboratorySheth M. N. Science College, Patan

Hemchandracharya North Gujarat University

Bio-active molecules

Therapeutic Studies

Heterocyclic Derivatives

Organic Synthesis

Lipinski’ s Rule of

Five

Spectral study

Introduction

Chapter 2

Chapter 4

Chapter 5

Chapter 6

Publications

Chapter 3

Introduction

Chapter 2

Chapter 4

Chapter 5

Chapter 6

Publications

Studies on 1,3,4-

oxadiazole derivatives

Studies on Benzoxazol

e derivatives

Studies on acetamide

clubbed with 1,3,4 oxadiazole

Studies on benzoxazole clubbed-schiff base

studies on 1,3,4-

oxadiazole-clubbed

Schiff bases

Chapter 3

Chapter 2

Literature review

Derivatives synthesized

Reaction procedure

Lipinski’s rule of 5

Spectral characterization

Antimicrobial activity

Studies on 1,3,4-oxadiazole derivatives

S

O

NN

CN

R

R: 3-NO2; 4-NO2; 4-Cl; 2-Cl; 3-Cl; 3-CH3; 4-CH3; H

Chapter 2

Literature review


Reaction procedure





1,3,4-oxadiazoles as potential antibacterial and antifungal agents

• references – 5 to 8 of chapter - 2

Chapter 2

Literature review


Reaction procedure





S

O

NN

CN

R

4'-(5-Aryl-[1,3,4]oxadiazol-2-ylsulfanylmethyl)-biphenyl-2-carbonitrilederivatives IIIa-h

Compounds

Substituent Nomenclature

IIIa m-NO2

4'-((5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-

carbonitrile

IIIb p-NO2

4'-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-

carbonitrile

IIIc p-Cl4'-((5-(4-chlorophenyl)-1,3,4-

oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile

IIId o-Cl4'-((5-(2-chlorophenyl)-1,3,4-


IIIe m-Cl4'-((5-(3-chlorophenyl)-1,3,4-


IIIf m-CH34'-((5-m-tolyl-1,3,4-oxadiazol-2-

ylthio)methyl)biphenyl-2-carbonitrile

IIIg p-CH34'-((5-p-tolyl-1,3,4-oxadiazol-2-

ylthio)methyl)biphenyl-2-carbonitrile

IIIh H 4'-((5-phenyl-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile

Chapter 2

Literature review


Reaction procedure





CONHNH2CS2 / KOH

Ethanol

N N

OSH

Step 1

2a-h1a-h

R R

N N

OSH

2a-h+

K2CO3 / acetone

R

IIIa-h

Step 2; 2a-h + II

CN

Br

S

O

NN

CN

R

II

Chapter 2

Literature review


Reaction procedure





4'-(5-Aryl-[1,3,4]oxadiazol-2-ylsulfanylmethyl)-biphenyl-2-carbonitrile derivatives IIIa-h

S

O

NN

CN

R

Entry Descriptors for Lipinski’s rule of five No. of violationM.W. Log P No. of

H-bond donor

No. ofH-bond

acceptor

IIIa 414 5.356 0 6 1

IIIb 414 5.356 0 6 1

IIIc 403 6.020 0 5 1

IIId 403 6.020 0 5 1

IIIe 403 6.020 0 5 1

IIIf 383 5.929 0 4 1

IIIg 383 5.929 0 4 1

IIIh 369 5.416 0 4 1

Chapter 2

Literature review


Reaction procedure





5 4

3

21

67

89

10

11 12

13

S14

O15

NN

16

17

18

19

20

21

ClNC

4'-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile

Functional group

Frequency (Cm-1)

-C-O-C- ring (str.) 1012,1270-C-H aromatic

ring(str.) 3058

-CH2 methylene group (str.) 2979

-C=C- aromatic ring (str.) 1489-CN (str.) 2221

Chapter 2

Literature review


Reaction procedure





5 4

3

21

67

89

10

11 12

H2C13

S14

O15

NN

16

17

18

19

20

21

ClNC H

H

HH

H

HH

H

H

H

H

H

4'-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile IIIc

Assignment No. of protons Multiplicity value

(ppm)-CH2 2 singlet 4.68Ar-H 12 multiplet 7.57-7.99

Chapter 1

Literature review


Reaction procedure





Peak assignment m/z value

M+1 peak 404.3

Chapter 2

Literature review


Reaction procedure





Compounds

Minimum Inhibitory Concentration (MIC) in µg/mlGram-positive

bacteriaGram-negative

bacteria Fungi

S. aureusATCC

25923

E. faecalis

ATCC 29212

E. coliATCC

25922

P. aerugino

saATCC

27853

C. albican

sATCC

10231

A. nigerATCC 1015

IIIa (R:m-NO2) 125 125 125 125 125 62.5IIIb (R:p-NO2) 62.5 125 62.5 62.5 250 62.5IIIc (R:p-Cl) 62.5 62.5 31.25 125 125 31.25IIId(R:o-Cl) 31.25 62.5 31.25 31.25 62.5 31.25IIIe(R:m-Cl) 62.5 62.5 15.62 31.25 125 62.5

IIIf(R:m-CH3) 250 125 125 250 250 125IIIg(R:p-CH3) 125 250 250 125 500 250

IIIh(R:H) 250 250 125 125 250 125Fluconazole - - - - 125 62.5Ciprofloxaci

n 62.5 125 125 125 - -

Chapter 3

Literature review


Reaction procedure




Studies on Benzoxazole derivatives

Cl

O

N

S HN

O

2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide

R

Chapter 3

Literature review


Reaction procedure





Reference

18

Reference 25

Antimicrobial agents

Chapter 3

Literature review


Reaction procedure




Studies on Benzoxazole derivativesCl

O

N

S HN

O


R

Compounds Substituent Nomenclature

III1 -4-COCH3N-(4-Acetyl-phenyl)-2-(5-chloro-benzo[d]oxazol-2-

ylsulfanyl)-acetamide

III2 -4-NO22-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(4-nitro-

phenyl)-acetamide

III3 -3-F-4-Cl 2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-(4-chloro-3-fluorophenyl)acetamide

III4 -3-NO22-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(3-nitro-

phenyl)-acetamide

III5 -H 2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-phenyl-acetamide

III6 -3-CH32-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-m-tolyl-

acetamide

III7 -2-CH32-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-o-tolyl-

acetamide

III8 -4-CH32-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-p-tolyl-

acetamide

III9 -2- NO22-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(2-nitro-

phenyl)-acetamide

III10 -4-F 2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(4-fluoro-phenyl)-acetamide

III11 3-OCH32-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(3-

methoxy-phenyl)-acetamide

III12 3-Cl 2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(3-chloro-phenyl)-acetamide

III13 2-OCH32-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(2-

methoxy-phenyl)-acetamide

III14 3-CF3 2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(3-trifluoromethyl-phenyl)- acetamide

Chapter 3

Literature review


Reaction procedure





Cl NH2

OH

CS2 / KOH

Ethanol / HClO

NCl

SH

Step 1

2-amino-4-chlorophenol 5-chlorobenzo[d]oxazole-2-thiol

NH2CAC / TEA

DMF

HNCl

OR

substituted anilines derivatives of 2-chloro-N-arylacetamide

R

Step 2

R= 4-COCH3; 4-NO2; 3-F-4-Cl; 3-NO2; H; 3-CH3; 2-CH3 4-CH3; 2-NO2; 4-F; 3-OCH3; 3-Cl; 2-OCH3; 3-CF3

Chapter 3

Literature review


Reaction procedure





O

NCl

SH

HNCl

O

II1-14

R+

Acetone / K2CO3

O

NCl

S

O

HN

Step 3

R

5-chlorobenzo[d]oxazole-2-thiol

2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide III 1-14

Chapter 3

Literature review


Reaction procedure




Studies on Benzoxazole derivativesCl

O

N

S HN

O

2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamideIII 1-14

R


H-bond donor

No. ofH-bond

acceptor

III1 360 3.395 1 5 0

III2 363 3.777 1 6 0

III3 371 4.584 1 6 0

III4 363 3.777 1 6 0

III5 318 3.837 1 4 0

III6 332 4.351 1 4 0

III7 332 4.351 1 4 0

III8 332 4.351 1 4 0

III9 363 3.777 1 6 0

III10 336 3.980 1 5 0

III11 348 3.395 1 5 0

III12 353 4.441 1 5 0

III13 348 3.395 1 5 0

III14 386 4.715 1 7 0

Chapter 3

Literature review


Reaction procedure





Cl

O

N

S HN

O


R

Functional groupFrequency (Cm-1) Functional group

Frequency (Cm-1)

-N-H sec. amine (str.) 3290 -C=O carbonyl group (str.) 1626

-C-H aromatic ring (str.) 3065 -C-Cl (str.) 691-CH2 methylene group

(str.) 2982 -C-O-C- ring (str.) 1027, 1335

Chapter 3

Literature review


Reaction procedure





Cl

O

N

S

H2C

HN

O

2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-(3-chlorophenyl)acetamideIII12

H

H

H

ClH

H

H H

Assignment No. of protons Multiplicity value (ppm)

-NH 1 singlet 10.66-CH2 2 Singlet 4.38Ar-H 7 Multiplet 7.141-7.395

Chapter 3

Literature review


Reaction procedure





Peak assignment

m/z value

M+1 peak 353.4

Chapter 3

Literature review


Reaction procedure





Compounds



bacteria Fungi

S. aureus

ATCC 25923

E. faecalis

ATCC 29212

E. coliATCC 25922

P. aerugino

saATCC

27853

C. albicans

ATCC 10231

A. nigerATCC 1015

III1 31.25 62.5 62.5 62.5 250 250

III2 31.25 62.5 62.5 62.5 250 250

III3 62.5 62.5 62.5 62.5 250 250

III4 62.5 62.5 62.5 31.25 500 500

III5 62.5 62.5 125 125 250 250

III6 31.25 62.5 31.25 31.25 250 125

III7 62.5 62.5 62.5 62.5 250 125

III8 62.5 62.5 31.25 125 62.5 125

III9 62.5 62.5 62.5 125 125 125

III10 62.5 62.5 62.5 125 125 125

III11 62.5 62.5 62.5 125 125 125

III12 62.5 62.5 62.5 62.5 62.5 62.5

III13 31.25 31.25 62.5 62.5 62.5 62.5

III14 31.25 31.25 125 125 62.5 62.5Fluconazole - - - - 125 62.5Ciprofloxaci

n 62.5 125 125 125 - -

Chapter 4

Literature review


Reaction procedure




Studies on acetamide clubbed 1,3,4-oxadiazole derivatives

R1= p-Cl; m-Cl; m-NO2; o-Cl; p-CH3

R= o-NO2; m-Cl; m-OCH3; p-F

O

NN

S

O

HN

R

R1

Chapter 4

Literature review


Reaction procedure





Ref-5

Ref-15

Antibacterial

Ref-9

Ref-18

Antifungal

Chapter 4

Literature review


Reaction procedure





R1= p-Cl; m-Cl; m-NO2; o-Cl; p-CH3

R= o-NO2; m-Cl; m-OCH3; p-F

O

NN

S

O

HN

R

R1


III1R1:p-Cl; R:m-Cl

2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide

III2R1:p-Cl; R:o-NO2

2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(2-nitrophenyl)acetamide

III3R1:p-Cl;

R:p-F2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-

fluorophenyl)acetamide

III4R1:p-Cl;

R:m-OCH3

2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-methoxyphenyl)acetamide

III5R1:m-Cl; R:m-Cl


III6R1:m-Cl; R:o-NO2


III7 R1:m-NO2; R:p-F 2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-fluorophenyl)acetamide

III8R1:m-NO2; R:m-

OCH3

2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-methoxyphenyl)acetamide

III9R1:o-Cl;R:o-NO2


III10R1:o-Cl; R: m-Cl


III11R1:o-Cl;

R:m-OCH3

2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-methoxyphenyl)acetamide

III12R1:o-Cl;

R:p-F2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-

fluorophenyl)acetamide

III13 R1:p-CH3; R:m-Cl 2-(5-p-tolyl-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide

Chapter 4

Literature review


Reaction procedure





CONHNH2CS2 / KOH

Ethanol

N N

OSH

Step 1

2a-e1a-e

R1 R1

NH2 HN

O

Cl

CAC / TEA

DMF

3A-D 4A-D

Step 2

R R

Chapter 4

Literature review


Reaction procedure




NH

O

Cl

4A-D

N N

OSH

2a-e+

K2CO3 / acetone

N N

OS

O

HN

R1

III1-13R1

Step 3 2a-e + 4A-D

R

R


Chapter 4

Literature review


Reaction procedure





N-Aryl-2-(5-phenyl-[1,3,4]oxadiazol-2-ylsulfanyl)- N-arylacetamide derivatives III1-13

O

NN

S

O

HN

R

R1


H-bond donor

No. ofH-bond

acceptor

III1 379 4.101 1 6 0

III2 390 3.437 1 7 0

III3 363 3.640 1 6 0

III4 375 3.055 1 6 0

III5 378 4.101 1 6 0

III6 390 3.437 1 7 0

III7 374 2.976 1 7 0

III8 386 2.391 1 7 0

III9 390 3.437 1 7 0

III10 378 4.101 1 6 0

III11 375 3.055 1 6 0

III12 363 4.101 1 6 0

III13 359 4.010 1 5 0

Chapter 4

Literature review


Reaction procedure




4

3

2

1

6

5 7

O8

NN

S

Cl

2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide III1

9

10

O

HN11

16 15

14

1312

Cl

Functional group Frequency (Cm-1) Functional group

Frequency (Cm-

1)

-N-H sec. amine (str.) 3239 -C=C- aromatic ring (str.) 1422

-C-H aromatic ring (str.) 3081 -C-Cl (str.) 682

-CH2 methylene group (str.) 2511 -C-O-C- ring (str.) 1013,

1277-C=O carbonyl group

(str.) 1671 -Nil- -Nil-


Chapter 4

Literature review


Reaction procedure




4

32

1

6

5 7

O8

NN

S

Cl

2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide III1

H2C

9

10

O

HN11

16 15

14

1312

Cl

H

H

H

H

H H

H

H


(ppm)-NH 1 singlet 10.652-CH2 2 singlet 4.36Ar-H 8 multiplet 7.35-7.98


Chapter 4

Literature review


Reaction procedure




Peak assignment

m/z value

M+1 peak 380.2


Chapter 4

Literature review


Reaction procedure




Compounds



bacteria Fungi

S. aureus

ATCC 25923

E. faecalis

ATCC 29212

E. coliATCC

25922

P. aerugino

saATCC

27853

C. albican

sATCC

10231

A. nigerATCC 1015

III1 (R1:p-Cl; R:m-Cl) 62.5 62.5 62.5 125 125 125III2 (R1:p-Cl; R:o-NO2) 250 62.5 250 125 125 125III3 (R1:p-Cl; R:p-F) 250 125 250 250 250 125III4 (R1:p-Cl; R:m-OCH3) 125 125 250 250 250 125III5 (R1:m-Cl; R:m-Cl) 125 250 62.5 62.5 250 125III6 (R1:m-Cl; R:o-NO2) 250 250 62.5 250 250 250III7 (R1:m-NO2; R:p-F) 250 250 250 500 250 125III8 (R1:m-NO2; R:m-OCH3) 250 125 250 250 125 250III9 (R1:o-Cl; R:o-NO2) 250 250 250 250 250 250III10 (R1:o-Cl; R: m-Cl) 250 125 250 250 250 250III11(R1:o-Cl; R:m-OCH3) 250 125 250 250 250 250III12(R1:o-Cl; R:p-F) 250 250 250 250 125 125III13(R1:p-CH3; R:m-Cl) 125 250 250 250 125 125Fluconazole - - - - 125 62.5Ciprofloxacin 62.5 125 125 125 - -


Chapter 5

Literature review


Reaction procedure




Studies on Benzoxazole clubbed-Schiff bases

O

NCl

NH N CH

N- aryl benzylidene-N'-(5-chloro-benzo[d]oxazol-2-yl)-hydrazinederivatives III1-11

R

Chapter 5

Literature review


Reaction procedure




Studies Benzoxazole clubbed Schiff bases

• Ref-24• Ref-25

Antibacterial

Chapter 5

Literature review


Reaction procedure





O

NCl

NH N CH


R


III1 -2-NO2N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(2-nitro-

benzylidene)-hydrazine

III2 -4-OH 4-[(5-Chloro-benzo[d]oxazol-2-yl)-hydrazonomethyl]-phenol

III3 -4-Cl N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(4-chloro-benzylidene)-hydrazine

III4 -3,4,5 triOCH3N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(3,4,5-

trimethoxy-benzylidene)-hydrazine

III5 -3-OH 3-[(5-Chloro-benzo[d]oxazol-2-yl)-hydrazonomethyl]-phenol

III6 -4-OH-3-OCH34-[(5-Chloro-benzo[d]oxazol-2-yl)-

hydrazonomethyl]-2-methoxy-phenol

III7 -N,N diCH3{4-[(5-Chloro-benzo[d]oxazol-2-yl)-

hydrazonomethyl]-phenyl}-dimethyl-amine

III8

-2-OH -1 Naphthaldehy

de1-[(5-Chloro-benzo[d]oxazol-2-yl)-

hydrazonomethyl]-naphthalene-2-ol

III9 -3-OH-4-OCH35-[(5-Chloro-benzo[d]oxazol-2-yl)-

hydrazonomethyl]-2-methoxy-phenol

III10 -2-5 diOCH3N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(2,5-

dimethoxy-benzylidene)-hydrazine

III11 -2,4,5 triOCH3N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(2,4,5-

trimethoxy-benzylidene)-hydrazine

Chapter 5

Literature review


Reaction procedure





Cl NH2

OH

CS2 / KOH

Ethanol / HClO

NCl

SH

Step 1

2-amino-4-chlorophenol 5-chlorobenzo[d]oxazole-2-thiol I

Step 2

O

NSH

ClNH2NH2.H2O

O

NNHNH2

Cl

1-(5-chlorobenzo[d]oxazol-2-yl)hydrazine II5-chlorobenzo[d]oxazole-2-thiol I

EtOH

Chapter 5

Literature review


Reaction procedure





Step 3

O

NCl

NHNH2

1-(5-chlorobenzo[d]oxazol-2-yl)hydrazine II

+

ROHC

Substituted aldehyde

EtOHCH3COOH

O

NNH N CH

RCl

N-aryl benzylidene-N'-(5-chloro-benzo[d]oxazol-2-yl)-hydrazine dervatives III1-11

Chapter 5

Literature review


Reaction procedure





O

NCl

NH N CH


R


H-bond donor

No. ofH-bond

acceptor

III1 318 4.285 1 5 0

III2 287 4.132 2 5 0

III3 306 5.040 1 5 1

III4 361 3.108 1 7 0

III5 287 4.132 2 5 0

III6 317 4.340 2 6 0

III7 314 4.544 1 5 0

III8 337 5.121 2 5 1

III9 317 4.340 2 6 0

III10 331 3.551 1 6 0

III11 361 3.108 1 7 0

Chapter 5

Literature review


Reaction procedure





4

3 1

6

5

O

7

N

NH N CH8

9

Cl

14 13

12

1110

Cl

N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(4-chloro-benzylidene)-hydrazine III3

2

Functional groupFrequency (Cm-1) Functional group

Frequency (Cm-1)

-N-H sec. amine (str.) 3412 -C-Cl (str.) 798-C-H aromatic ring (str.) 3095 -C-O-C- ring (str.) 1092, 1322-C=N sec. amine (str.) 1591 -C-H alkene (str.) 3180

Chapter 5

Literature review


Reaction procedure





O

N

NH N CH

Cl

O2N

N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(2-nitro-benzylidene)-hydrazine III1

H

H

H

H

H

HH


(ppm)-NH 1 singlet 12.31-CH 1 Singlet 4.025Ar-H 7 Multiplet 7.60-8.62

Chapter 5

Literature review


Reaction procedure




Peak assignment

m/z value

M+1 peak 317.2


Chapter 5

Literature review


Reaction procedure





Compounds

Minimum Inhibitory Concentration (MIC) in µg/ml

Gram-positive bacteria

Gram-negative bacteria Fungi

S. aureus

ATCC 25923

E. faecalis

ATCC 29212

E. coliATCC 25922

P. aerugino

saATCC 27853

C. albicans

ATCC 10231

A. nigerATCC 1015

III1 250 125 125 250 125 125III2 250 125 125 250 125 125III3 250 125 500 250 250 125III4 250 125 500 250 250 125III5 250 125 500 125 250 125III6 250 500 500 250 500 500III7 250 500 250 125 500 500III8 125 500 250 125 250 250III9 125 500 250 125 250 250III10 250 500 500 250 500 500III11 250 500 500 250 500 500

Fluconazole - - - - 125 62.5

Ciprofloxacin 62.5 125 125 125 - -

Chapter 6

Literature review


Reaction procedure




Studies on 1,3,4-oxadiazole clubbed-Schiff bases

2-(2-arylbenzylidenehydrazinyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole III1-11

Cl

O

NN

NH

N CH

R

Chapter 6

Literature review


Reaction procedure





Ref-11

Ref-12

Ref-17

ANTIMICROBIAL AGENT

S

Chapter 6

Literature review


Reaction procedure






Cl

O

NN

NH

N CH

R


III1 -4-OH 4-{[5-(4-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-hydrazonomethyl}-phenol

III2 -4-Cl N-(4-Chloro-benzylidene)-N'-[5-(4-chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-hydrazine

III3 -4-NO2N-[5-(4-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-N'-(4-

nitro-benzylidene)-hydrazine

III4 -3,4,5-triOCH32-(3,4,5-trimethoxybenzylidene)-1-(5-(4-

chlorophenyl)-1,3,4-oxadiazol-2-yl)hydrazine

III5 -2,5-diOCH32-(2,5-dimethoxybenzylidene)-1-(5-(4-

chlorophenyl)-1,3,4-oxadiazol-2-yl)hydrazine

III6 -2,4,5-triOCH32-(4-chlorophenyl)-5-(2-(2,4,5-

trimethoxybenzylidene)hydrazinyl)-1,3,4-oxadiazole

III7 -2-NO22-(4-chlorophenyl)-5-(2-(2-

nitrobenzylidene)hydrazinyl)-1,3,4-oxadiazole

III8-2-OH-1-

Napthaldehyde1-((2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-

yl)hydrazono)methyl)naphthalen-2-ol

III9 N,N-diCH34-((2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)hydrazono)methyl)-N,N-dimethylaniline

III10 -4-OH-3-OCH34-((2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-

yl)hydrazono)methyl)-2-methoxyphenol

III11 3-OH 3-((2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)hydrazono)methyl)phenol

Chapter 6

Literature review


Reaction procedure




O

NHNH2

CS2 / KOH

Ethanol / HCl

NN

OHS

Step 1

Cl

4-chlorobenzohydrazideCl

5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol II

Step 2

Cl

O

NN

SH

II

NH2NH2.H2OEtOH

O

NN

NHNH2

Cl1-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-

yl)hydrazine

D


Chapter 6

Literature review


Reaction procedure




+

EtOH/Gla. acetic acid

Step 3

O

NN

NHNH2

Cl1-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)hydrazine

R

OHC

Substituted aryl aldehyde

Cl

O

NN

NH

N CH

R

2-(2-arylbenzylidenehydrazinyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole derivatives III1-11


Chapter 6

Literature review


Reaction procedure





Cl

O

NN

NH

N CH

R



H-bond donor

No. ofH-bond

acceptor

III1 314 3.792 2 6 0

III2 333 4.699 1 6 0

III3 343 4.035 1 7 0

III4 388 2.768 1 8 0

III5 358 3.210 1 7 0

III6 388 2.768 1 8 0

III7 343 4.035 1 7 0

III8 364 4.781 2 6 0

III9 341 4.203 1 6 0

III10 344 3.999 2 7 0

III11 314 3.792 2 6 0

Chapter 6

Literature review


Reaction procedure




4

3

2 1

6

5

Cl7

O9

8

NN

NH N CH9

10

15 14

13

1211

Cl

N-(4-Chloro-benzylidene)-N'-[5-(4-chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-hydrazine III2

Functional group Frequency (Cm-1) Functional group Frequenc

y (Cm-1)

-N-H sec. amine (str.) 3248 -C=C- aromatic ring (str.) 1426

-C-H aromatic ring (str.) 3150 -C-N- sec. amine (str.) 1319

-C-O-C- ring (str.) 1017, 1235 -Nil- -Nil-


Chapter 6

Literature review


Reaction procedure




Cl O

NN

NH N CH Cl

N-(4-Chloro-benzylidene)-N'-[5-(4-chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-hydrazine III2

HH

HH

H H

HH


(ppm)-NH 1 Singlet 14.261-CH 1 Singlet 5.809Ar-H 8 Multiplet 7.108-7.914


Chapter 6

Literature review


Reaction procedure





Peak assignment m/z value

M+1 peak 333.9

Chapter 6

Literature review


Reaction procedure




Compounds



bacteria Fungi

S. aureus

ATCC 25923

E. faecalisA

TCC 29212

E. coliATCC

25922

P. aerugin

osaATCC 27853

C. albicansATCC 10231

A. nigerA

TCC 1015

III1 125 250 250 125 125 250III2 125 250 125 125 250 250III3 125 250 125 125 250 250III4 125 250 125 125 125 250III5 62.5 250 62.5 125 250 250III6 62.5 250 62.5 125 250 250III7 62.5 250 62.5 125 250 250III8 62.5 250 125 125 250 250III9 62.5 250 125 125 250 250III10 125 250 125 125 250 250III11 125 250 125 125 250 250

Fluconazole - - - - 125 62.5Ciprofloxacin 62.5 125 125 125 - -


THANK YOU

Presentation for viva

Science

Transcript of Presentation for viva