Synthesis and Identification of some Benzoxazole Derivatives via Mannich Reaction

The p-Hydroxybenzyldehyde is one of the aromatic compounds which contains two important functional groups (OH, CHO). In this work, the p-hydroxybenzyldehyde has been introduced into different reactions. The first one involves the synthesis of ether via Williamson reaction, in which p-hydroxybenzyldehyd reacts with chloroacetic acid to afford compound (1), then compound (1) in presence of sodium bicarbonate gives the anion (2). Which reacts with propargyl bromide to give the acetylenic compound (3). The compound (3) in turn reacts with secondary amine via Mannich reaction to give the acetylenic amines(4a-f). Finally, the compounds (4a-f) undergo reaction with o-amino phenol to give benzoxazole derivatives (5a-f). The structure of synthesized compounds had been elucidated by the available physical and spectral data.

Mannich reaction involves reaction of compounds containing active hydrogen with formaldehyde and amminonia, primary or secondary amine. Mannich reaction has been employed in the organic synthesis of neutral compounds such as peptides, nucleotides, antibiotics, and alkaloids (Hussin, 2009). Other applications were in agrochemicals such as plant growth, regulators (DaRosa, 2003). The Mannich products (acetylenic amine derivatives) were considered pharmaceutically active compounds for possessing several biological activities such as antispasmodic (Sheat and Ali, 2005), hypertensive (Sheat and Dawood, 2005) anticancer (Al- Iraqi and Yahya, 2009), and antibacterial activities (Sheat and Saeed, 2006).

EXPERIMENTAL
Melting points were determined using electrothermal 9300 melting point apparatus and are uncorrected. The IR spectra were recorded on pye-Unicam SP1100 spectraphotometer as (KBr) disc. UV spectra were recorded on Shimadzu (UV-160) UV-visible spectrophotometer using CHCl3 as a solvent.

Preparation of benzoxazoline derivatives (5a-f) (Gupta, 2011):
To a stirred solution of the compounds (4a-f) (0.011 mole) in ethanol, sodium bisulfite (0.0023 mole, 5 g) was added at room temperature. Then a solution of o-aminophenol (0.0023 mole, 5 g) in dimethylformamide (20 ml) was added and boiled under reflux for 3 hr. The reaction mixture was poured on an ice cold water (20 ml) and the precipite formed was filtered off and recrystallized from ethanol. The physical and spectroscopic data of synthesized compounds (5a-f) were listed in (Table 2).

RESULTS AND DISCUSSION
The synthetic route in this research was illustrated in scheme 1.The IR spectrum of compound (1) showed characteristic absorption bands at the region: 3060 cm -1 for the O-H bond stretching, (2852,2918) cm -1 for the aliphatic C-H stretching vibration, 1677and 1724 cm -1 for the c=o bond stretching of the formyl and carboxyl moieties, in addation to absorption bond at 1238 and 1053 cm -1 for the asy. and sy. c-o-c bond. The UVspectrum showed λ max at (254) nm. The other supporting evidence for this compound is the negative ferric chloride test.
To synthesize the ester (3), the carboxylic acid was treated with sodium bicarbonate to produce the enolate anion (2) which upon treatment with propargyl bromide afforded the propargyl ester (3). The IR spectrum of compound (2) showed a strong band at 1240 and 1163 cm -1 for the asy. And sy. c-o-c bond stretching respectively. The UV spectrum of compound (2) showed λ max at (256) nm.
The spectrum of compound (3) showed characteristic absorption bands: 1761 and 1677 cm -1 for the ester and aldehydic c=o bond stretching, at 2123 cm -1 for the c≡c bond stretching and at 3250 cm -1 for the ≡C-H bond stretching. The UV spectrum of compound (3) showed λ max at (256) nm due to the (n π*) electronic transition. The other supporting evidence for the formation of this compound is the positive tollens test for the terminal acetylenic compounds. The acetylenic compound (3) was converted to the Mannich base by its reaction with secondary amines in presence of paraformaldehyde. The structure investigation of the synthesized acetylenic amines derivatives (4a-f) was achieved according to their physical and spectroscopic data (IR, UV) ( Table 1).
Other supporting evidences are that the acetylenic hydrogen in compound (3) showed positive Tollens test which become test negative in Mannich products (4a-f) The aldehydic group can be used to synthesize the benzoxazoline derivatives (5a-f) by its reaction with o-amino phenol. The formation of these compounds was proceeded according to the following suggested mechanism.
IR spectra of compounds (5a-f) as indicated in Table (2) show strong absorption band for benzoxazole at (1558-1572)cm -1 . The disapperance of the absorption bands for the aldehydic band stretching in the range of (1715-1695) cm -1 give a good indication for the formation of the oxozoline ring in compounds (5a-f).