My PhD Presentation

1. SYNTHESIS OF HETEROCYCLIC
COMPOUNDS AND EVALUATION OF
THEIR BIOLOGICAL ACTIVITIES
Mr. Abhishek R. Joshi
C/O Dr. K S Parikh (Research Guide & Principal)
Chemistry Research Laboratory
Sheth M. N. Science College, Patan
Hemchandracharya North Gujarat University

2. 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

3. Introduction
Chapter 2
Chapter 4
Chapter 5
Chapter 6
Publications
Chapter 3

4. Chapter 2
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
S
O
N
N
CN
R
R: 3-NO2; 4-NO2; 4-Cl; 2-Cl; 3-Cl; 3-CH3; 4-CH3; H

5. Chapter 2
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
1,3,4-oxadiazoles as
potential antibacterial
and antifungal agents
•references – 5 to 8 of
chapter - 2

6. Chapter 2
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
S
O
N
N
CN
R
4'-(5-Aryl-[1,3,4]oxadiazol-2-ylsulfanylmethyl)-biphenyl-2-carbonitrile
derivatives IIIa-h
Compound
s
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-Cl
4'-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-
ylthio)methyl)biphenyl-2-carbonitrile
IIId o-Cl
4'-((5-(2-chlorophenyl)-1,3,4-oxadiazol-2-
ylthio)methyl)biphenyl-2-carbonitrile
IIIe m-Cl
4'-((5-(3-chlorophenyl)-1,3,4-oxadiazol-2-
ylthio)methyl)biphenyl-2-carbonitrile
IIIf m-CH3
4'-((5-m-tolyl-1,3,4-oxadiazol-2-
ylthio)methyl)biphenyl-2-carbonitrile
IIIg p-CH3
4'-((5-p-tolyl-1,3,4-oxadiazol-2-
ylthio)methyl)biphenyl-2-carbonitrile
IIIh H
4'-((5-phenyl-1,3,4-oxadiazol-2-

7. Chapter 2
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
CONHNH2
CS2 / KOH
Ethanol
N
N
O
SH
Step 1
2a-h1a-h
R R
N
N
O
SH
2a-h
+
K2CO3 / acetone
R
IIIa-h
Step 2; 2a-h + II
CN
Br
S
O
N
N
CN
R
II

8. Chapter 2
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
4'-(5-Aryl-[1,3,4]oxadiazol-2-ylsulfanylmethyl)-biphenyl-2-carbonitrile derivatives IIIa-h
S
O
N
N
CN
R
Entry Descriptors for Lipinski’s rule of five No. of
violationM.W. Log P No. of
H-bond
donor
No. of
H-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

9. Chapter 2
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
5 4
3
21
67
89
10
11 12
13
S
14
O15
N
N
16
17
18
19
20
21
Cl
NC
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

10. Chapter 2
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
5 4
3
2
1
67
89
10
11 12
H2C
13
S
14
O15
N
N
16
17
18
19
20
21
Cl
NC 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 4.68
Ar-H 12 multiplet 7.57-7.99

11. Chapter 1
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Peak
assignment
m/z value
M+1 peak 404.3

12. Chapter 2
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Compounds
Minimum Inhibitory Concentration (MIC) in µg/ml
Gram-positive bacteria
Gram-negative
bacteria
Fungi
S. aureus
ATCC
25923
E. faecalis
ATCC
29212
E. coli
ATCC
25922
P.
aeruginos
a
ATCC
27853
C.
albicans
ATCC
10231
A. niger
ATCC
1015
IIIa (R:m-NO2) 125 125 125 125 125 62.5
IIIb (R:p-NO2) 62.5 125 62.5 62.5 250 62.5
IIIc (R:p-Cl) 62.5 62.5 31.25 125 125 31.25
IIId(R:o-Cl) 31.25 62.5 31.25 31.25 62.5 31.25
IIIe(R:m-Cl) 62.5 62.5 15.62 31.25 125 62.5
IIIf(R:m-CH3) 250 125 125 250 250 125
IIIg(R:p-CH3) 125 250 250 125 500 250
IIIh(R:H) 250 250 125 125 250 125
Fluconazole - - - - 125 62.5
Ciprofloxacin 62.5 125 125 125 - -

13. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Cl
O
N
S HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide
R

14. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Reference
18
Reference
25
Antimicrobial
agents

15. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Cl
O
N
S HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide
R
Compounds Substituent Nomenclature
III1 -4-COCH3
N-(4-Acetyl-phenyl)-2-(5-chloro-benzo[d]oxazol-2-
ylsulfanyl)-acetamide
III2 -4-NO2
2-(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-NO2
2-(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-CH3
2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-m-tolyl-
acetamide
III7 -2-CH3
2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-o-tolyl-
acetamide
III8 -4-CH3
2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-p-tolyl-
acetamide
III9 -2- NO2
2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(2-nitro-
phenyl)-acetamide
III -4-F
2-(5-Chloro-benzo[d]oxazol-2-ylsulfanyl)-N-(4-fluoro-

16. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Cl NH2
OH
CS2 / KOH
Ethanol / HCl
O
NCl
SH
Step 1
2-amino-4-chlorophenol 5-chlorobenzo[d]oxazole-2-thiol
NH2
CAC/ TEA
DMF
H
N
Cl
O
R
substituted anilines derivatives of2-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

17. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
O
NCl
SH
H
N
Cl
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

18. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Cl
O
N
S HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide
III 1-14
R
Entry Descriptors for Lipinski’s rule of five No. of
violationM.W. Log P No. of
H-bond
donor
No. of
H-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

19. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Cl
O
N
S HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide
R
Functional group
Frequency
(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

20. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Cl
O
N
S
H2C
HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-(3-chlorophenyl)acetamide
III12
H
H
H
ClH
H
H H
Assignment No. of protons Multiplicity  value (ppm)
-NH 1 singlet 10.66
-CH2 2 Singlet 4.38
Ar-H 7 Multiplet 7.141-7.395

21. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Peak assignment m/z value
M+1 peak 353.4

22. Chapter 3
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Compounds
Minimum Inhibitory Concentration (MIC) in µg/ml
Gram-positive
bacteria
Gram-negative bacteria Fungi
S. aureus
ATCC
25923
E. faecalis
ATCC
29212
E. coli
ATCC
25922
P.
aeruginosa
ATCC
27853
C. albicans
ATCC
10231
A. niger
ATCC
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 62.5
Fluconazole - - - - 125 62.5
Ciprofloxacin 62.5 125 125 125 - -

23. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
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

24. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Ref-5
Ref-15
Antibacterial
Ref-9
Ref-18
Antifungal

25. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
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
Compounds Substituent Nomenclature
III1
R1:p-Cl;
R:m-Cl
2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-
chlorophenyl)acetamide
III2
R1:p-Cl;
R:o-NO2
2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(2-
nitrophenyl)acetamide
III3
R1:p-Cl;
R:p-F
2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-
fluorophenyl)acetamide
III4
R1:p-Cl;
R:m-OCH3
2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-
methoxyphenyl)acetamide
III5
R1:m-Cl;
R:m-Cl
2-(5-(3-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-
chlorophenyl)acetamide
III6
R1:m-Cl;
R:o-NO2
2-(5-(3-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(2-
nitrophenyl)acetamide
III7 R1:m-NO2; R:p-F
2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-
fluorophenyl)acetamide
III8 R1:m-NO2; R:m-OCH3
2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-
methoxyphenyl)acetamide
III9
R1:o-Cl;
R:o-NO2
2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(2-
nitrophenyl)acetamide
III10
R1:o-Cl;
R: m-Cl
2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-
chlorophenyl)acetamide
III11
R1:o-Cl;
R:m-OCH3
2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-
methoxyphenyl)acetamide
III12
R1:o-Cl;
R:p-F
2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-
fluorophenyl)acetamide
III R :p-CH ; R:m-Cl 2-(5-p-tolyl-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide

26. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
CONHNH2
CS2 / KOH
Ethanol
N
N
O
SH
Step 1
2a-e1a-e
R1 R1
NH2 HN
O
Cl
CAC/ TEA
DMF
3A-D 4A-D
Step 2
R R

27. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
NH
O
Cl
4A-D
N
N
O
SH
2a-e
+
K2CO3 / acetone
N
N
O
S
O
HN
R1
III1-13
R1
Step 3 2a-e + 4A-D
R
R

28. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
N-Aryl-2-(5-phenyl-[1,3,4]oxadiazol-2-ylsulfanyl)- N-arylacetamide derivatives III1-13
O
NN
S
O
HN
R
R1
Entry Descriptors for Lipinski’s rule of five No. of
violationM.W. Log P No. of
H-bond
donor
No. of
H-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

29. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
4
3
2
1
6
5 7
O
8
NN
S
Cl
2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide
III1
9
10
O
HN
11
16 15
14
1312
Cl
Functional group
Frequenc
y (Cm-1)
Functional group
Frequenc
y (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
1671 -Nil- -Nil-

30. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
4
3
2
1
6
5 7
O
8
NN
S
Cl
2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide
III1
H2
C
9
10
O
HN
11
16 15
14
1312
Cl
H
H
H
H
H H
H
H
Assignment No. of protons Multiplicity  value (ppm)
-NH 1 singlet 10.652
-CH2 2 singlet 4.36
Ar-H 8 multiplet 7.35-7.98

31. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Peak
assignment
m/z
value
M+1 peak 380.2

32. Chapter 4
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Compounds
Minimum Inhibitory Concentration (MIC) in µg/ml
Gram-positive
bacteria
Gram-negative bacteria Fungi
S. aureus
ATCC
25923
E. faecalis
ATCC
29212
E. coli
ATCC
25922
P.
aeruginosa
ATCC
27853
C.
albicans
ATCC
10231
A. niger
ATCC
1015
III1 (R1:p-Cl; R:m-Cl) 62.5 62.5 62.5 125 125 125
III2 (R1:p-Cl; R:o-
NO2) 250 62.5 250 125 125 125
III3 (R1:p-Cl; R:p-F) 250 125 250 250 250 125
III4 (R1:p-Cl; R:m-
OCH3) 125 125 250 250 250 125
III5 (R1:m-Cl; R:m-
Cl) 125 250 62.5 62.5 250 125
III6 (R1:m-Cl; R:o-
NO2) 250 250 62.5 250 250 250
III7 (R1:m-NO2; R:p-
F) 250 250 250 500 250 125
III8 (R1:m-NO2; R:m-
OCH3) 250 125 250 250 125 250
III9 (R1:o-Cl; R:o-
NO2) 250 250 250 250 250 250
III10 (R1:o-Cl; R: m-
Cl) 250 125 250 250 250 250
III11(R1:o-Cl; R:m-
OCH3) 250 125 250 250 250 250

33. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
O
N
Cl
NH N CH
N- aryl benzylidene-N'-(5-chloro-benzo[d]oxazol-2-yl)-hydrazine
derivatives III1-11
R

34. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
•Ref-24
•Ref-25
Antibacterial
•Ref-26
•Ref-27
Antifungal

35. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
O
N
Cl
NH N CH
N- aryl benzylidene-N'-(5-chloro-benzo[d]oxazol-2-yl)-hydrazine
derivatives III1-11
R
Compounds Substituent Nomenclature
III1 -2-NO2
N-(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 triOCH3
N-(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-OCH3
4-[(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
Naphthaldehyd
e
1-[(5-Chloro-benzo[d]oxazol-2-yl)-
hydrazonomethyl]-naphthalene-2-ol
III9 -3-OH-4-OCH3
5-[(5-Chloro-benzo[d]oxazol-2-yl)-
hydrazonomethyl]-2-methoxy-phenol
N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(2,5-

36. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Cl NH2
OH
CS2 / KOH
Ethanol / HCl
O
NCl
SH
Step 1
2-amino-4-chlorophenol 5-chlorobenzo[d]oxazole-2-thiol I
Step 2
O
N
SH
Cl
NH2NH2.H2O
O
N
NHNH2
Cl
1-(5-chlorobenzo[d]oxazol-2-yl)hydrazine II5-chlorobenzo[d]oxazole-2-thiol I
EtOH

37. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Step 3
O
NCl
NHNH2
1-(5-chlorobenzo[d]oxazol-2-yl)hydrazine II
+
R
OHC
Substituted aldehyde
EtOH
CH3COOH
O
N
NH N CH
R
Cl
N-aryl benzylidene-N'-(5-chloro-benzo[d]oxazol-2-yl)-hydrazine
dervatives III1-11

38. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
O
N
Cl
NH N CH
N- aryl benzylidene-N'-(5-chloro-benzo[d]oxazol-2-yl)-hydrazine
derivatives III1-11
R
Entry Descriptors for Lipinski’s rule of five No. of
violationM.W. Log P No. of
H-bond
donor
No. of
H-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

39. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
4
3 1
6
5
O
7
N
NH N CH
8
9
Cl
14 13
12
11
10
Cl
N-(5-Chloro-benzo[d]oxazol-2-yl)-N'-(4-chloro-benzylidene)-hydrazine
III3
2
Functional group
Frequency
(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

40. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
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
Assignment No. of protons Multiplicity  value (ppm)
-NH 1 singlet 12.31
-CH 1 Singlet 4.025
Ar-H 7 Multiplet 7.60-8.62

41. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Peak
assignment
m/z
value
M+1 peak 317.2

42. Chapter 5
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Compounds
Minimum Inhibitory Concentration (MIC) in µg/ml
Gram-positive
bacteria
Gram-negative
bacteria
Fungi
S. aureus
ATCC
25923
E.
faecalis
ATCC
29212
E. coli
ATCC
25922
P.
aeruginos
a
ATCC
27853
C.
albicans
ATCC
10231
A. niger
ATCC
1015
III1 250 125 125 250 125 125
III2 250 125 125 250 125 125
III3 250 125 500 250 250 125
III4 250 125 500 250 250 125
III5 250 125 500 125 250 125
III6 250 500 500 250 500 500
III7 250 500 250 125 500 500
III8 125 500 250 125 250 250
III9 125 500 250 125 250 250
III10 250 500 500 250 500 500
III11 250 500 500 250 500 500
Fluconazole - - - - 125 62.5
Ciprofloxacin 62.5 125 125 125 - -

43. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
2-(2-arylbenzylidenehydrazinyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole III1-11
Cl
O
NN
N
H
N C
H
R

44. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Ref-11
Ref-12
Ref-17

45. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
2-(2-arylbenzylidenehydrazinyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole III1-11
Cl
O
NN
N
H
N C
H
R
Compounds Substituent Nomenclature
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-NO2
N-[5-(4-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-N'-(4-nitro-
benzylidene)-hydrazine
III4 -3,4,5-triOCH3
2-(3,4,5-trimethoxybenzylidene)-1-(5-(4-chlorophenyl)-
1,3,4-oxadiazol-2-yl)hydrazine
III5 -2,5-diOCH3
2-(2,5-dimethoxybenzylidene)-1-(5-(4-chlorophenyl)-1,3,4-
oxadiazol-2-yl)hydrazine
III6 -2,4,5-triOCH3
2-(4-chlorophenyl)-5-(2-(2,4,5-
trimethoxybenzylidene)hydrazinyl)-1,3,4-oxadiazole
III7 -2-NO2
2-(4-chlorophenyl)-5-(2-(2-nitrobenzylidene)hydrazinyl)-
1,3,4-oxadiazole
III8
-2-OH-1-
Napthaldehyde
1-((2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-
yl)hydrazono)methyl)naphthalen-2-ol
III9 N,N-diCH3
4-((2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-
yl)hydrazono)methyl)-N,N-dimethylaniline
III10 -4-OH-3-OCH3
4-((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

46. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
O
N
H
NH2
CS2 / KOH
Ethanol / HCl
N
N
O
HS
Step 1
Cl
4-chlorobenzohydrazide
Cl
5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol II
Step 2
Cl
O
NN
SH
II
NH2NH2.H2O
EtOH
O
NN
NHNH2
Cl
1-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-
yl)hydrazine
D

47. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
+
EtOH/ Gla. acetic acid
Step 3
O
NN
NHNH2
Cl
1-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)hydrazine
R
OHC
Substituted aryl aldehyde
Cl
O
NN
N
H
N C
H
R
2-(2-arylbenzylidenehydrazinyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole derivatives III1-11

48. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
2-(2-arylbenzylidenehydrazinyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole III1-11
Cl
O
NN
N
H
N C
H
R
Entry Descriptors for Lipinski’s rule of five No. of
violationM.W. Log P No. of
H-bond
donor
No. of
H-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

49. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
4
3
2
1
6
5
Cl
7
O
9
8
NN
NH N CH
9
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
Frequency
(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-

50. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Cl O
NN
NH N CH Cl
N-(4-Chloro-benzylidene)-N'-[5-(4-chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-hydrazine
III2
H
H
H
H
H H
HH
Assignment No. of protons Multiplicity  value (ppm)
-NH 1 Singlet 14.261
-CH 1 Singlet 5.809
Ar-H 8 Multiplet 7.108-7.914

51. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Peak
assignment
m/z value
M+1 peak 333.9

52. Chapter 6
Literature review
Derivatives
synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral
characterization
Antimicrobial activity
Compounds
Minimum Inhibitory Concentration (MIC) in µg/ml
Gram-positive
bacteria
Gram-negative
bacteria
Fungi
S. aureus
ATCC
25923
E.
faecalisAT
CC 29212
E. coli
ATCC
25922
P.
aerugino
sa
ATCC
27853
C.
albicans
ATCC
10231
A.
nigerAT
CC
1015
III1 125 250 250 125 125 250
III2 125 250 125 125 250 250
III3 125 250 125 125 250 250
III4 125 250 125 125 125 250
III5 62.5 250 62.5 125 250 250
III6 62.5 250 62.5 125 250 250
III7 62.5 250 62.5 125 250 250
III8 62.5 250 125 125 250 250
III9 62.5 250 125 125 250 250
III10 125 250 125 125 250 250
III11 125 250 125 125 250 250
Fluconazole - - - - 125 62.5
Ciprofloxacin 62.5 125 125 125 - -