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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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole derivatives
1,3,4-oxadiazoles as potential antibacterial and antifungal agents
• references – 5 to 8 of chapter - 2
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
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-
oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile
IIIe m-Cl4'-((5-(3-chlorophenyl)-1,3,4-
oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole derivatives
Peak assignment m/z value
M+1 peak 404.3
Chapter 2
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivatives
Cl
O
N
S HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide
R
Chapter 3
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivatives
Reference
18
Reference 25
Antimicrobial agents
Chapter 3
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivativesCl
O
N
S HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivativesCl
O
N
S HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamideIII 1-14
R
Entry Descriptors for Lipinski’s rule of five No. of violationM.W. Log P No. of
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivatives
Cl
O
N
S HN
O
2-(5-chlorobenzo[d]oxazol-2-ylthio)-N-arylacetamide
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivatives
Peak assignment
m/z value
M+1 peak 353.4
Chapter 3
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on Benzoxazole derivatives
Compounds
Minimum Inhibitory Concentration (MIC) in µg/mlGram-positive
bacteriaGram-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 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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on acetamide clubbed 1,3,4-oxadiazole derivatives
Ref-5
Ref-15
Antibacterial
Ref-9
Ref-18
Antifungal
Chapter 4
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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
Compounds Substituent Nomenclature
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
2-(5-(3-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide
III6R1: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
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
2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(2-nitrophenyl)acetamide
III10R1:o-Cl; R: m-Cl
2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(3-chlorophenyl)acetamide
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on acetamide clubbed 1,3,4-oxadiazole derivatives
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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
Studies on acetamide clubbed 1,3,4-oxadiazole derivatives
Chapter 4
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on acetamide clubbed 1,3,4-oxadiazole derivatives
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. 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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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-
Studies on acetamide clubbed 1,3,4-oxadiazole derivatives
Chapter 4
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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
Assignment No. of protons Multiplicity value
(ppm)-NH 1 singlet 10.652-CH2 2 singlet 4.36Ar-H 8 multiplet 7.35-7.98
Studies on acetamide clubbed 1,3,4-oxadiazole derivatives
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
Studies on acetamide clubbed 1,3,4-oxadiazole derivatives
Chapter 4
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Compounds
Minimum Inhibitory Concentration (MIC) in µg/mlGram-positive
bacteriaGram-negative
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 - -
Studies on acetamide clubbed 1,3,4-oxadiazole derivatives
Chapter 5
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies Benzoxazole clubbed Schiff bases
• Ref-24• Ref-25
Antibacterial
Chapter 5
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies Benzoxazole clubbed Schiff bases
O
NCl
NH N CH
N- aryl benzylidene-N'-(5-chloro-benzo[d]oxazol-2-yl)-hydrazinederivatives III1-11
R
Compounds Substituent Nomenclature
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies Benzoxazole clubbed Schiff bases
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies Benzoxazole clubbed Schiff bases
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies Benzoxazole clubbed Schiff bases
O
NCl
NH N CH
N- aryl benzylidene-N'-(5-chloro-benzo[d]oxazol-2-yl)-hydrazinederivatives III1-11
R
Entry Descriptors for Lipinski’s rule of five No. of violationM.W. Log P No. of
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies Benzoxazole clubbed Schiff bases
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies Benzoxazole clubbed Schiff bases
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 4.025Ar-H 7 Multiplet 7.60-8.62
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
Studies Benzoxazole clubbed Schiff bases
Chapter 5
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies Benzoxazole clubbed Schiff bases
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole clubbed-Schiff bases
Ref-11
Ref-12
Ref-17
ANTIMICROBIAL AGENT
S
Chapter 6
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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
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-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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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
Studies on 1,3,4-oxadiazole clubbed-Schiff bases
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
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
Studies on 1,3,4-oxadiazole clubbed-Schiff bases
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
NH
N CH
R
Studies on 1,3,4-oxadiazole clubbed-Schiff bases
Entry Descriptors for Lipinski’s rule of five No. of violationM.W. Log P No. of
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
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
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-
Studies on 1,3,4-oxadiazole clubbed-Schiff bases
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
HH
HH
H H
HH
Assignment No. of protons Multiplicity value
(ppm)-NH 1 Singlet 14.261-CH 1 Singlet 5.809Ar-H 8 Multiplet 7.108-7.914
Studies on 1,3,4-oxadiazole clubbed-Schiff bases
Chapter 6
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Studies on 1,3,4-oxadiazole clubbed-Schiff bases
Peak assignment m/z value
M+1 peak 333.9
Chapter 6
Literature review
Derivatives synthesized
Reaction procedure
Lipinski’s rule of 5
Spectral characterization
Antimicrobial activity
Compounds
Minimum Inhibitory Concentration (MIC) in µg/mlGram-positive
bacteriaGram-negative
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 - -
Studies on 1,3,4-oxadiazole clubbed-Schiff bases
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