REGISTRATION OF SUBJECT FOR DISSERTATION

A PROTOCOL FOR THE PROJECT WORK ENTITLED

“SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL

ACTIVITY STUDIES OF 1, 3, 4 OXADIAZOLES.”

By,
Sufeera.K(koilotra)
M.Pharm, Part- I
Department of Pharmaceutical Chemistry
N.G.S.M. Institute of Pharmaceutical Sciences
Paneer, Deralakatte,
Mangalore – 574160.

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 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE
KARNATAKA.

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME OF THE SUFEERA.K(koilotra)

CANDIDATE N.G.S.M INSTITUTE OF PHARMACEUTICAL SCIENCES
AND ADDRESS PANEER, DERALAKATTE, MANGALORE – 574160.
2. NAME OF THE N.G.S.M. INSTITUTE OF PHARMACEUTICAL SCIENCES,
INSTITUTION PANEER, DERALAKATTE, MANGALORE – 574160.
3. COURSE OF M.PHARM
STUDY AND [PHARMACEUTICAL CHEMISTRY]
SUBJECT
4. DATE OF JUNE 2007
ADMISSION
5. Title of the Topic :
“SYNTHESIS,CHARACTERIZATION AND BIOLOGICAL ACTIVITY
STUDIES OF 1,3,4 OXADIAZOLES”
6. Brief Resume of the Intended Work :
6.1 Need for the study:
Oxadiazoles are five membered heterocyclic compounds with two
nitrogen atoms and one oxygen atom. They are synthesized by ring condensation
and rearrangement reactions.

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 Depending on the position of heteroatoms they are named 1, 2, 3-1, 2, 4-
1, 2, 5 and 1, 3, 5 oxadiazoles .All of them were reported to posses one or the
other biological activities.
From the review 1-4 of literature it was found that 1, 3, 4 oxadiazoles
posses antimicrobial1, analgesic, antiinflammatory2,, antibacterial3, anticancer4, ,
antifungal 5 and tuberculostatic6 activities.
By considering the above factors it was thought to synthesize some
oxadiazole derivatives and investigate their biological activity.

6.2 Review of Literature:

1. Reddy VM et al., (1997)7 synthesised 2-aryl amino-5- (2-amino phenyl )-1,3,4

oxadiazoles, 2-aryl amino-5- (2-amino phenyl)-1,3,4 thiadiazoles and 2-aryl
amino-2-mercapto-1,2,3,4-tetrahydro-5H by cyclisation (by dehydro
sulphurization of 1-(2-amino benzoyl )-4-aryl-3-thiosemicarbazides.

2. Wadodkar KN and Dhiman., (2001) 8 synthesised 1, 3, 4 oxadiazole by

cyclocondensation reaction of 1- (3-aryl-1H-5 pyrazole-5-yl)-4-substituted
thiosemicarbazides with 2N potassium hydroxide solution and with Iodine/KI in
alkaline condition. The structures of these compounds were established on the
basis of their elemental analysis and spectral data and evaluated for their
antimicrobial activity against gram positive and gram negative bacteria.

3. Khan MSY and Akhtar ., (2003)9 synthesized 2-(coumarin-3-yl)-5-aryl-1, 3, 4,

oxadiazole derivatives by condensing hydrazide of 3-carbethoxy coumarin with
various aromatic acids. In aother method 4-methyl-1-7(5-phenyl-1,3,4-
oxadiazole-2-yl methoxy )coumarin and 4-methy-7- (5-amino-1,3,4-oxadiazo-2-
yl methoxy coumarin prepared by condensing-4-methyl coumarinyl-7-oxy acetic
hydrazide. The entire oxadiazole derivatives were tested for their anti-
inflammatory, analgesic and antimicrobial activity.

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4. Jain S et al., (2004)10 synthesized 5-aryl 1, 3, 4, oxadiazole-2-thione by
refluxing aromatic carboxylic acid hydrazides with carbon disulfide and
methanolic potassium hydrooxide. The entire compounds were screened for their
in vivo antibacterial activity.

5. Mogilaiah and Prashanthi., (2005)11 synthesized 5-aryl-2-{p-1, 8-

naphthyridin-2-yl} phenoxy methy1oxadiazole by oxidative cyclization of [p-(1,
8 naphthy ridin-2-yl)-phenoxy methyl] acetic acid arylidine-hydrazides with
chloramine-T. The structures of the compounds have been established on the
basis of their elemental analysis and spectral (IR, 1H NMRand MS) data.

6. Mogilaiah K and Vidya k., (2006)12 synthesized 1-(4-acetyl -5-aryl -5-methyl

{1, 3, 4,} oxadiazole -2-yl-methy1)-3-phenyl-1H- {1,8}naphthyridin-2-ones) by
treatment of acetophenone (2-oxo-3-phenyl-2H-[1, 8] naphthyridine-1-yl] methyl
carbonyl hydrazones with acetic anhydride which was obtained by condensation
of (2-oxo-3-pheyl-2H [1,8] naphthyridin-1yl acetic acid hydrazide with different
acetophenones. The structures of the compounds have been confirmed on the
basis of analytical and spectral data.

7. Vagdevi HM et al., (2006)13 synthesized-3-acetyl-5- naphtha (2,1-b)furan-2-yl -2

aryl-2,3dihydro -1,3,4oxadiazoles and 2-naphtho [2,1-b] furan 2-yl -5 aryl 1,3,4
oxadizole by cyclization of N1 (IE)- aryl methylene)-naphtho
[2, 1-b] furan-2-carboxy hydrazides with acetic anhydride and mercuric oxide
which was obtained by condensation of naphtho [2, 1-b] furan-2-carboxy
hydrazide. All the newly synthesized compounds were characterized by
elemental analysis and spectral studies. The selected compounds were screened
for their antimicrobial and anti-inflammatory activities.
8. Sarangapani M et al., (2006)14 synthesized 2-(2-substituted benzoxazol-5-yl)-5-

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 aryl-1, 3, 4-oxadiazole by condensation of appropriate acid hydrazides with
different aromatic aldehydes and subsequent reaction with chloramine-T. The
compounds were characterized by spectral data (IR, PMR and Mass)
9. Ingole S Priyadarshani et al., (2007)15 synthesized 2-substituted-5-(pyrid-4-yl)
1, 3,4oxadizoles by oxidative cyclization of substituted isoniazids with molecular
iodine in presence of alkali in ethanolic medium. All these compounds were
screened for their antimicrobial activity against gram positive and gram negative
microorganisms.

10. Mohd Amir et al., (2007)16 synthesized by treatment of 2,4,6-trichlophenoxy

acetic acid hydrazide with CS2 and KOH. Which was obtained by treating 2,4,6-
trichlorophenol with ethylchloro acetate in presence of anhydrous
K2CO3 followed by reaction with hydrazine hydrate in absolute ethanol. The
compounds, which show good anti-inflammatory activity, have been screened for
their ulcerogenic and lipid peroxidation activities.
6.3 Objectives of the study:
The present study is performed with the following objectives.
1. Synthesis of some-1, 3, 4 oxadiazole derivatives.
2. Characterization of the new synthesized compounds by spectral data.
3. Screening for the analgesic and anti-inflammatory activities.
Materials and methods:
7.1 Sources of data.
 Journals and publications.
 CD ROM and internet.
 Laboratory based studies.
7.2 Methods of collection of data.
 From available literature.
 From library based books.
 Websites.

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 -www.pubmed.com
-www.google.com
-www.sciencedirect.com
7.3 Does the study require any investigations or interventions to be
conducted on patients or other humans or animals?
If so please describe briefly
Yes.
Male/female albino rats will be tested for pharmacological investigation.

7.4 Has ethical clearance been obtained your institution in case of 7.3?
Applied.
LIST OF REFERENCE.

1. Ingole S Priyadarshini, Mohane SR, Berad BN. Synthesis and antimicrobial

activity of 2-alkyl -aryl -5-(Pyrid-4-yl)-1, 3, 4-oxadiazole. Asian J Chem 2007

April; 19: 2683-86.

2. Amir Mohmed, Javed SA, Harish Kumar. Synthesis of some 1,3,4 oxadiazole

derivatives as potential anti-inflammatory agents. Ind J Chem 2007 June; 46B:

1014-19.

3. Siddiqui N, Khan SA, Bhat A Mashooq. Synthesis and antibacterial activity of

coumarin incorporated 1,3,4 oxadiazoles. Ind J Het Chem 2005 Jan.-March;

14: 271-2

4. Shivarama Holla B, Narayana Poojary K, Subrahmanya Bhat K, Mithun

Ashok, Boja Poojary. Synthesis and anticancer activity studies on some 2-

Chloro-1, 4-bis-(-substituted -1,3,4-oxadiazole-2-yl methyl enoxy) phenylene

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 derivatives. Ind J Chem 2005 Aug; 44B: 1669-73.

5. Atmaram Mishra, Dharm Veer Singh, Rakesh Mani Mishra. Synthesis, antifungal
activity of new 1,3,4 oxadiazolo(3,2-b)-s-triazine-5-ones and their thiones
analogues. Ind J Het Chem 2005 April-June; 14: 289-92.

6. Rafal Franski. Biological activities of the compounds bearing 1,3,4-oxa(thia)

diazole ring. Asian J Chem 2005 April; 17: 2063-75.

7. Reddy VM, Reddy PSN, Reddy PCS, Ratmanc V. Cyclisation by dehydro

sulphurization of 1-(2-amino benzoyl )-4-aryl-3 thio semicarbazides: Formation of
1, 3, 4 benzotriazepinones, 1, 3, 4 thiadiazoles and 1, 3, 4 oxadiazoles.
Ind J Het Chem 1997 Juty-Sep; 7: 17-20.

8. Wadodkar AM, Dhiman. Synthesis and antimicrobial study of heterocyclyl

substituted S-triazoles, 1, 3, 4-thiadiazoles, oxadiazoles and related heterocycles.

Ind J Chem 2001July; 40B: 636-9.

9. Khan MSY, Akhtar M. Synthesis of some new 2,5 disubstituted 1,3,4-

oxadiazole derivatives and their biological activities. Ind Chem 2003 July-Sept.;

42B: 900-04.

10. Jain S, Pradeep Mishra. Synthesis and antibacterial activity of 5-acyl thio-

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1,3,4 -oxadiazoles. Ind J Het Chem 2004 April-June; 13: 307-10.

11. Mogilaiah K, Prashanthi. A convenient synthesis of 5-aryl-2(P-(1,8-

naphthyridin -2-yl) phenoxy methyl )-1,3,4 oxadiazoles under microwave

irradiation. Ind J Het Chem 2005 Jan.-March; 14: 185-8.

12. Mogilaiah K, Vidya K. Synthesis and antibacterial activity of 1,3,4-

oxadiazolyl-1,8 naphthyridines Ind J Chem 2006 Aug.; 45B: 1905-08.

13. Vagdevi HM, Ravindra KC, Vaidya VP, Vasavaraj Padmashali. Synthesis,

antimicrobial and anti-inflammatory activities of 1,3,4-oxadiazoles linked to

naphtha(2,1-b) furan. Ind J Chem 2006 Nov.; 45B: 2506-11.

14 Sarangapani M, Sreedhar D, Arjun M, Jyothi M, Raviprasad T. Synthesis of

some new 2-(2-substituted benzoxazole -5-yl)-5-aryl -1,3,4-oxadiazoles.

Ind J Het Chem 2006 July- sep.; 16: 61-2.

15. Amir Mod, Shikha Kumar. Synthesis of some new 2,5 disubstituted 1,3,4

oxadiazole derivatives and their anti-inflammatory activity. Ind J Het Chem 2004

July-Sept.; 14: 51-54.

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 SCHEME
R K2CO3,ClCH2COOC2H5 R

Acetone,heat

NH2 NHCH2COOC2H5

Alcohol, heat 6hrs NH2NH2.H 2O,

NHCH2CONHNH2

Alcohol GAA R CHO,heat 6hrs.

NHCH2 C NH N= C R
H

DMF,48 hrs,stirring HgO/I2

N N

NHCH2 R
O

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