Synthesis of 1,3,4-Oxadiazole

 

Maqdoom Farooqui¹, Syed Nazimuddin¹

P.G. and Research Centre, Maulana Azad College of Arts, Science and Commerce, Aurangabad

*Corresponding Author E-mail: maqdoomf@gmail.com

Synthesis of 1,3,4-oxadiazole by the reaction of 2-propyl Benzo imidiazol-2-yl carbohydrazide and 1,3, dihydro iso indo-2-yl acetic acid (Phthalyl Amino Acids) in presence of HCl and phosphoryl chloride. All the newly synthesized compounds were screened antibacterial activity which shows moderate to mild activity, and yield of the synthesized compounds were found to be 62-68 %.

 

 

 

INTRODUCTION:

Oxadiazole is important heterocyclic ring present in a large number of biological active molecules of different pharmacological classes it is known to have fungicidal, bacterial and herbicidal activities. Oxadiazole is a five membered heterocyclic ring which is a versatile lead compound for designing potent   bioactive   agents.   This   interesting   group   of   compound   has   diverse   biological activities   such   as   antimicrobial, anti-inflammatory, antitubercular, anticonvulsant, anticancer, anti-HIV, hypoglycemic and genotoxic. Given data represents that oxadiazole being heterocyclic planar five membered ring systems have various pharmacological   actions. 

 

A series of oxadiazole Mannich bases by reaction between oxadiazole derivatives were synthesized ^[1], dapsone, appropriate aldehydes and was evaluated against Mycobacterium Tuberculosis. Some new 3-acetyl-5-(3-chloro-1 benzo[6]thiophen-2-yl)-2-substituted phenyl-2,3-dihydro-1,3,4-oxadiazoles and 2-(3-chloro-1- benzo[6]thiophen-2-yl)-5-substituted phenyl-1,3,4-oxadiazoles were  synthesized^[2]   and was evaluated for Anti­microbial activity.  Compounds were found to be most potent against activates, even better than the standard drugs i.e. ciprofloxacin.

 

New compounds of   1,3,4-oxadiazole from different compounds were synthesized^[3] and was tested for Anti- microbial activity on different strains. Number of new 1,3,4-oxadiazole derivatives and 1,2,4-triazine-5-one derivatives were synthesized^[4]. All the compounds were screened for their Anti-inflammatory activity by using carrageen in-induced rat paw edema method.  Compounds were synthesized^[5]  6-Methyl-4-aryl-5-(5- phenyl-1, 3, 4-oxadiazol-2-yl)-1,2,3,4- tetrahydropyrimidine-2(1H)-one significant effect against Streptococcus pneumonia (+ve) and 3b has significant activity effect Escheria coli (-ve).

Some 3-acetyl-2-substituted phenyl-5-(3,4,5-Tri methoxy phenyl)-2,3-dihydro-1,3,4-oxadiazole derivatives was synthesized ^[6].  All the synthesized compounds highly active against PC3 cells and are moderately active against Bcap37 and BGC823 cells. A series of 5-[3’-oxo-6’-(substituted aryl)-2’,3’,4’,5’-tetrahydropyridazin-2i-ylmethyl]-2-substituted 1,3,4-oxadiazole was synthesized ^[7] and then final compounds were tested for their anti- bacterial activity using cup plate method. All the synthesized compounds found to be most potent derivative as compared to the standard drug.

 

Novel compounds of 1,3,4-oxadiazole with 2-fluoro-4-methoxy moiety was synthesized^[8] and are tested for Anti-Microbial activity and all synthesized compounds showed significant anti-bacterial activity against Escherichia coli and Pseudomonas Aeruginosa, showed anti-fungal activity against C. Albicans.

 

Fifteen novels (E)-methoxy imino-benzene acetate derivatives were synthesized ^[9]. Bioassays indicated that compound showed potent fungicidal activity against Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Physalospora piricola and Bipolaris mayclis and showed potent fungicidal activity against R. Solani. Series of novel ether-linked bis (heterocycles) was synthesized ^[10] . All the synthesized compounds were screened for anti-inflammatory and analgesic activities and showed excellent activity against ibuprofen and aspirin.  A series of novel 2, 5-disubstituted 1,3,4-oxadiazole derivatives was synthesized^[11] and was tested for in. vitro Anti-Microbial activity. 2-(2-naphthyloxy methyl)-5-phenoxymethyl-1,3,4-oxadiazole exhibited > 90% inhibition among all the synthesized compounds. Derivatives of oxadiazoles was synthesized^[12] and are evaluated for their ability to inhibit tubulin polymerization and to arrest mitotic division of tumor cells.

 

A series of five membered heterocyclic were synthesized ^[13] and was tested for convulsion. From the synthesized compounds (IIf) 2-(4-chlorophenyl) amino-5-(4-pyridyl)-1,3,4-thiadiazole and (IIIf) 2-(4-chlorophenyl)amino-5-(4-pyridyl)-1, 3, 4oxadiazole showed potent activity. Some compounds using the key intermediates 5-(3,4,5-trimethoxyphenyl)-1,3,4-thiadiazole-2-thiol or the oxadiazole analogue were synthesized^[14] and tested for fungicidal activity. From all the synthesized compounds can inhibit mycelia growth by approximately 50% in vitro against ten kinds of fungus. Novel compound of S-substituted phenacryl 1,3,4-oxadiazole and Schiff bases derived from 2-[(2,6-dichloroanilino) phenyl] acetic acid (diclofenac acid) ^[15].

 

EXPERIMENTAL AND SPECTRAL STUDIES:

Melting points were determined using open capillary method and are uncorrected. The compounds were checked for homogeneity by TLC on silica gel G. The IR spectra were recorded by using JASCO FTIR spectro photometer (Model 4100) using KBr-disc method.

 

 

RESULT AND DISCUSSION:

 

 

A mixture of 2-(2propyl-1H-benzimidiazol-yl) acetic acid hydrazide (0.002 mole), (0.003 mole) phthalyl amino acid (1,3-Dioxo-1,3-dihydro-isoindole-2-yl)-acetic acid and (1ml) phosphoryl chloride was heated for 30 min. Completion of reaction was monitored by TLC Mobile Phase Ethyl Acetate:Hexane (5:10) , the content were cooled to room temperature and added excess of ice cold water. The solid product was separated was collected and neutralized with dil NaOH solution, the solid product separated was collected and filtered. Further purification was done by recrystalized from ethanol DMF mixture (2:1) the yield and m.p. was recorded.

 

Table No. 1 Elemental Analysis of Synthesized Compounds (1a-d)

	R	Mol for/ Mol Wt	C	H	N	O
1a	H	C22H19N5O3 401	65.83	4.77	17.45	11.96
1b	C6H4-CH2	C29H25N5O3 491	70.86	5.13	14.25	09.76
1c	CH-Me2	C25H25N5O3 443	67.70	5.68	15.79	10.82
1d	CH3	C23H21N5O3 415	66.49	5.09	16.86	11.55

 

Table No. 2 Physical properties and IR values of synthesized compound (1a-d):

					IR(KBr)
COMP	R	%YLD	MP ̊C	Mol.Form/ Mol.Wt	C-H	C=N	C=O	C-O-C
1a	H	62	193-195	C22H19N5O3 401	3000	1600	1710	1160
1b	C6H4-CH2	65	182-185	C29H25N5O3 491	3025	1610	1716	1040
1c	CH-Me2	62	142-145	C25H25N5O3 443	3040	1600	1720	1040
1d	CH3	68	123-126	C23H21N5O3 415	3050	1610	1716	1030

 

 

Table No. 3 Results of antimicrobial activity of the tested compounds

Comp.No.	B. cereus	E.Coli	S.cerevisae	A.niger
Gentamycin	+++	+++	_	_
Ampicillin	+++	+++	_	_
1 a	+++	++	_	_
1b	+++	++	_	_
1c	++	++	_	_
1d	++	++	_	_

Highly active = +++  (inhibition zone>12mm); Moderately active = ++ (inhibition zone 9-12mm); Slightly active  =  + (inhibition zone 6-9mm)

 

Fig. 1 Inhibited area of tested compounds

 

CONCLUSION:

All the newly synthesized compounds (1a-d) were screened for antibacterial activity studies at a concentration of 600ug/disc as a control and Gentamycin used as standard against gram +ve and gram –ve bacteria. All the newly synthesized compounds showed moderate to mild antimicrobial activity. These findings concluded that the titled compounds have the property to kill the microbes in some extent when compared with standard drugs.     

Highly active = +++       (inhibition zone>12mm)

Moderately active = ++       (inhibition zone 9-12mm)                                                

Slightly active  =   +           (inhibition zone 6-9mm)

 

REFERENCES:

[1]   Mohamed Ashraf Ali, Mohammad Shaharyar, Bioorganic and Medicinal Chemistry Letters, (2007),1 7, 3314–3316.

[2]   Rakesh Chawla, Anshu Arora, Manoj Kumar Parameshwaran, Prabodh Chander Sharma,Sukumar Michael, Thengungal Kochupappy Ravi, Acta Poloniae Pharmaceutical ñ DrugResearch, (2010),Vol. 67 No. 3 pp., 247-253.

[3]   Nitin Bhardwaj, S.K. Saraf, Pankaj Sharma, Pradeep Kumar, Syntheses, E-Journal of Chemistry (2009), 6(4), 1133-1138.

[4]   Harish Kumar, Sadique A. Javed, Suroor A. Khan, Mohammad Amir, European Journal of Medicinal Chemistry, (2008), 43,2688-2698.

[5]   Manish Kumar Mishra, A K Gupta, S Negi, Meenakshi Bhatt,  International Journal of Pharma Sciences and Research (IJPSR), (2010),Vol.1(3),, 172-177.

[6]   Linhong Jin, Jiang Chen, Baoan Song, Zhuo Chen, Song Yang, Qianzhu Li, Deyu Hu and Ruiqing Xu, Bioorganic and Medicinal Chemistry Letters, (2006), 16,5036–5040.

[7]   Mojahidul Islam, Anees Siddiqui, Ramadoss Rajesh, Afroz Bakht and Sunil Goyal, Acta Poloniae Pharmaceutica n Drug Research, (2008), Vol. 65 No. 4 pp., 441-447.

[8]   B. Chandrakantha, Prakash Shetty, Vijesh Nambiyar, Nishitha Isloor, Arun M. Isloor, European Journal of Medicinal Chemistry, (2010), 45, 1206–1210.

[9]   Yan Li, Jie Liu, Hongquan Zhang, Xiangping Yanga and Zhaojie Liu, Bioorganic and Medicinal Chemistry Letters, (2006), 16, 2278–2282.

[10]         B. Jayashankar, K.M. Lokanath Rai , N. Baskaran, H.S. Sathish, European Journal of Medicinal Chemistry, (2009), 44, 3898–3902.

[11]         M. Shahar Yar, A. Ahmad Siddiqui and M. Ashraf Ali, Journal of the Chinese Chem.Society, (2007), 54, 5-8.

[12]         Xiaohu Ouyang, Evgueni L. Piatnitski, Vatee Pattaropong, Xiaoling Chen, Hai-Ying He, Alexander S. Kiselyov, Avdhoot Velankar, Joel Kawakami, Marc Labelle, Leon Smith, II, Julia Lohman, Sui Ping Lee, Asra Malikzay, James Fleming, Jason Gerlak, Ying Wang, Robin L.Rosler, Kai Zhou, Stan Mitelman, Margarita Camara, David Surguladze, Jacqueline F. Doodyand M. Carolina Tuma, Bioorganic and Medicinal Chemistry Letters, (2006), 16 1191–1196.

[13] Mohammad Shaharyar, Mohammad Wasim Akhter, Acta Poloniae Pharmaceutica n DrugResearch, (2009), Vol. 66 No. 4 pp.,393-397.

[14]         Cai-Jun Chen, Bao-An Song, Song Yang, Guang-Fang Xu, Pinaki S. Bhadury,Lin-Hong Jin,De-Yu Hu, Qian-Zhu Li, Fang Liu, Wei Xue, Ping Lu and Zhuo Chen, Bioorganic and Medicinal Chemistry, (2007), 15, 3981–3989.

[15]         Shashikant V. Bhandari, Kailash G. Bothara, Mayuresh K. Raut, Ajit A. Patil, Aniket P.Sarkate and Vinod J. Mokale, Bioorganic and Medicinal Chemistry, (2008), 16, 1822–1831.

 

 

 

Received on 10.02.2017         Modified on 21.02.2017

Accepted on 18.03.2017         © AJRC All right reserved