SYNTHESIS AND PHYSICO-CHEMICAL ANALYSIS OF 2-SUBSTITUTED BENZOXAZOL – 5-CARBOXYLIC ACID ARYLIDENE HYDRAZIDES

About author :
Ramesh Dhani
JNTUA-OTRI, Anantapur, India
Dept. of Pharmaceutical Chemistry
E-mail: [email protected]

ABSTRACT:
Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with oxygen and nitrogen separated by one carbon. Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak base; its conjugate acid has a pKa of    of 0.8, compared to 7 for imidazole. Oxazole is a heterocyclic organic compound that has a five-member ring molecular structure, containing oxygen, nitrogen as heteroatoms at its 1, 3-positions. Benzoxazoles are derivatives of oxazoles. Benzoxazoles is a planar molecule with conjugated p electrons sextets in the cyclic systems. In the current research work, the title compounds synthesis and physico-chemical analysis of 2-substituted benzoxazol – 5-carboxylic acid arylidene derivatives. By using different synthetic methods new Benzoxazole derivatives were synthesized and characterized by physic-chemical analysis, benzoxazole is a lead nucleus for future developments to get effective compounds.
Key words: Benzoxazole, Oxazole, Flunoxaprofen, Ethanol
Introduction :
The main objective of the medicinal chemistry is to synthesize the compounds that show promising activity as therapeutic agents with lower toxicity. Benzoxazoles have been reported to show a broad spectrum of biological activities. Notable among these are antihistaminic antifungal, Cyclooxygenase Inhibiting, antitumor, anticonvulsant, hypoglycemic, anti-inflammatory and antitubercular, antiulcer, activity. The pharmacological properties of  Benzoxazoles encouraged our interest in synthesizing several new compounds Benzoxazoles is a planar molecule with conjugated p electrons sextets in the cyclic systems. The lone pair of electrons on (N) nitrogen, which is coplanar with heterocyclic  ring and therefore not involved in the delocalization, confers weakly basic properties. Oxazole (1) is a heterocyclic organic compound that has a five-member ring molecular structure, containing oxygen, nitrogen as heteroatoms at its 1, 3-positions.  Benzoxazoles are derivatives of oxazoles. Benzoxazole (M.P. 27-30°C; B.P. 182°C) is an aromatic organic compound with a molecular formula C7H5NO, a benzene-fused oxazole ring structure; appearance is white to light yellow solid and an odour similar to pyridine. Other name of benzoxazole is 1-oxa-3-aza-1H-indene.  It is used primarily in industry and research. Benzoxazoles is a planar molecule with conjugated p electrons sextets in the cyclic systems.
Experimental :
1. Synthesis of 2-substituted-benzoxazol-5-carboxylic acid hydrazides 
A mixture of an appropriate 2-substituted-5-carbomethoxy benzoxazole ( 0.01 mol) in alcohol (25 ml) and hydrazine hydrate (99%, 0.015 mol) was heated under reflux, on water bath for 4 hours.  The alcohol was reduced to half of its volume and cooled.  The product separated was filtered and washed with small portions of cold alcohols first and then with cold water, repeatedly and dried.  The product was purified by recrystallization from suitable alcohol, dimethyl formamide (1:1) to get white crystalline solid.
2. Synthesis of 2-substituted benzoxazol-5-carboxylic acid arylidene hydrazides 
A mixture of appropriate 2-substituted benzoxazol-5-carboxylic acid hydrazides ( 0.01mol) and appropriate aldehyde (0.015 mol) in alcohol (20 ml) with 2 to 3 drops of acetic acid, heated under reflux on a water bath for one hour.  The solvent was removed to possible extent by distillation under reduced pressure.  The product thus obtained was filtered, washed with water dried and purified by recrystallization from suitable solvent.
3. Preliminary Analysis of the sample:
Thin-layer chromatography (TLC) was commonly used in the qualitative description of the complexity and composition of chemical mixtures.
Application of sample on TLC plates:
The sample was applied to the chromatogram by repeated “spotting” above 1-2 cm from one end of the plate with a capillary tube.
The most important precaution was not to apply spots below the level of the top of the solvent system in developing chamber
Developing solvent systems:
Development chamber was used for developing chromatogram. Alcohol: Dimethyl formamide (1:1) was the solvent system used for running TLC of these compounds.
Visualization of chromatogram:
After developing, the TLC plates were dried and then exposed to iodine vapours in a chamber, since chromatograms of many synthetic products were frequently observed by iodine vapors. Rf value was noted down. Purity of all the synthesized compounds including intermediates was checked by TLC on silica gel G plates. All compounds have shown only single spot indicating the completion of the reaction and thepurity of the product obtained.
Results :
The synthesized benzoxazole derivatives were recrystallized from alcohol and purified by thin layer chromatography [TLC], further characterized by physico-chemical analysis, it yields good product was found to be 85%.
Conclusion :
By this studies concluded that to find the structure-activity relationship and to optimize the structure. The synthesized benzoxazole derivative i.e., 2-substituted benzoxazol-5-carboxylic acid arylidene hydrazides was characterized by physicochemical analysis, the purity of the compound was checked by TLC, the solvent used here [alcohol: dimethyl formamide (1:1)] to get white crystalline solid.