Synthesis and Characterization of Novel Benzoxazole Schiff Base Derivatives

1.1 Chemistry Of Benzoxazole

A heterocyclic compound or ring structure is a cyclic compound  that has atoms of at least two different elements as member of  its rings. Among all the heterocyclic compounds, benzoxazole¹ is one of the most important  heterocyclic exhibiting  remarkable pharmacological activities. Benzoxazoles is a organic compound, which has benzene fused with oxazole ring, oxazole² is 1,3-azole having oxygen atom and a pyridine type nitrogen atom at 3-position in a five membered ring.

The electronegativity of the N- atom attracts electrons  so that C-2 is partially electropositive and therefore susceptible to nucleophilic attack. However, electrophilic substitution  of oxazoles takes place at the electron -rich position C-5 preferentially. More relevant to palladium  chemistry, 2-halooxazoles or 2-halobenzoxazoles are prone to oxidative addition to pd(0). Even 2- chlorooxazole and 2- chlorobenzoxazole are viable substrates for the pd-catalyzed reactions.

1.2 Synthesis of halobenzoxazoles

1.2.1. Sandmeyer reaction 

While halogenation and Sandmeyer reaction are suitable for preparation of oxazolyl halides, benzoxazolyl halides with halogen on the benzene ring moiety may be synthesized via other approaches. For instance, 5-halobenzoxazoles⁴ were prepared by treating 4-halo-2-aminophenols with trimethyl orthoformate and concentrated aqueous HCL^.

1.2.2. Carbonylation

2-Aryl and 2-heteroaryl-bezoxazoles were prepared by Pd- catalyzed three-component condensation of aryl halides with o-aminophenols  and carbonmonoxide followed by the dehydrative cyclisation^8,9. A variant of such methodology using o-flourephenylamines in place of o-aminophenols was used to synthesized arylbenzoxazoles.

1.2.3 Other Reactions of  benzoxazole

1.2.3.(A) Reaction with acids

2-aminophenols  can cyclize to benzoxazoles in the presence of carboxylic acids of upon heating to high temperature in the presence of a dehydrating agent (polyphosphoric acid, phosphorous pentoxide- methanesulphonic acid , H3BO3)⁵. When equimolar amounts of  2-aminophenols and alkyl or arylcarboxylic acids are heated to temperature of 140-220^oC are required for the formation of the corresponding 2-alkyl  or 2-arylbenzoxazoles.

1.2.3.(B)  Reaction with aldehydes

2-arylbenzoxazoles were directly synthesized from substituted 2-aminophenols and aldehydes in the presence of activated carbon in xylene under and oxygen atmosphere. A simple and efficient protocol as been developed for the synthesis of 2-arylbenzoxazole derivatives of potential  pharmaceutical interest. The method involves reaction between 2-aminophenol  and substituted aromatic aldehydes in the presence of anhydrous bismuth tricholoride as a catalyst in acetonitrile.

2. METHODOLOGY

SYNTHESIS

The scheme of synthesis for the designed benzoxazole derivatives was depicted below in scheme.

SCHEME:

2- (2-Ariginomethyelene) hydrazyl) benzo [d] oxazole IV

3. PROCEDURE

3.1 PREPARATION OF BENZO [D] OXAZOLE-2-THIOL

10.9g of 2-aminophenol,6.19ml of carbon disulphide, 5.65g of potassium hydroxide,15ml of water taken in a 250 ml RBF and refluxed in 100ml of 95% ethanol for 3-4 hours . Later charcoal was added continuously , refluxed for 10 minutes and filtered, the filtrate was heated up to 70-80⁰C and 100ml warm water was added, 5% glacial acetic acid was added and stirred vigorously. The product was obtained as crystals and placed refrigerator for 3h for further crystallization. The product was filtered and dried. The dried product was recrystallized with ethanol.

3.2 PREPARATION   OF 2-HYDRAZINYLBENZO [d] OXAZOLE

Equimolar quanities of benzo[d]oxazole and 99% hydrazine hydrate were dissolved in methanol and kept reflux for 20-22 hrs. The precipitate obtained was filtered washed with cold alcohol and dried.

3.3 GENERAL PREPARTION OF SCHIFF’ BASE(IVA-E)

An appropriate aromatic aldehyde and 2-hydrazinylbenzo[d]oxazole(III) were dissolved in methanol , 1-2 drops glacial acetic acid was added and refluxed for 6-8h.The mixture was kept in refrigerator overnight. The product  obtained was filtered, dried and purified by recrystallization.

4. Physical data of 2-(2-Ariginomethyelene) hydrazyl) benzo[d]oxazole IV

Spectral data of  : 2-(2-Ariginomethyelene) hydrazyl) benzo[d]oxazole IV

• Molecular formula: C₁₄H₉N₅O₅
• Mol .wt: 327
• IR (KBr) cm-1:

• CH-2795.34cm,CH-2908.97cm, CH-27
• CH-1660.90cm,CH-1594.92cm

• ¹H NMR (300 MHz) (DMSO):.

• NH-10.58 CH-8.55
• CH-7.39  CH-8.78
• CH-8.59CH-7.72

• Mass spectrum (ESI)  mass peak was observed at 327.

IR Spectral data of 2-(2-Ariginomethyelene) hydrazyl) benzo[d]oxazole IV

IR (KBr) cm^-1

• CH-2795.34cm,CH-2908.97cm, CH-27
• CH-1660.90cm,CH-1594.92cm

NMR Spectral data of  2-(2-Ariginomethyelene) hydrazyl) benzo[d]oxazole IV

¹H NMR (300 MHz) (DMSO):.

• NH-10.58 CH-8.55
• CH-7.39  CH-8.78
• CH-8.59CH-7.72

Mass Spectral data of 2-(2-Ariginomethyelene) hydrazyl) benzo[d]oxazole IV

Mass spectrum (ESI)  mass peak was observed at 327.