Mechanism of Polyphosphoric Acid and Phosphorus Pentoxide−Methanesulfonic Acid as Synthetic Reagents for Benzoxazole Formation

Abstract

The mechanism of 2-phenylbenzoxazole formation from benzoic acid and o-aminophenol in polyphosphoric acid (PPA) is studied by NMR spectroscopy and chemical analysis. Benzoic acid reacts with PPA to form benzoic-phosphoric anhydride and benzoic-polyphosphoric anhydride. The ratio of mixed anhydride to free carboxylic acid increases dramatically as the P 2 O 5 content of PPA increases, but this ratio is independent of reaction temperature and time. When o-aminophenol dissolves in PPA, part of the hydroxyl group is converted to phosphate ester, and only protonated amine is detected. Benzoic acid, mixed anhydride, and PPA are in dynamic equilibrium, and so are PPA, o-aminophenol, and its phosphate ester. The mixed anhydride and o-aminophenol react to form 2-aminophenyl benzoate as the first reaction intermediate which undergoes rapid acyl migration to generate 2-hydroxybenzanilide. Ring closure of 2-hydroxybenzanilide to form 2-phenylbenzoxazole is acid catalyzed. The reactive components in phosphorus pentoxidemethanesulfonic acid (P 2 O 5 -MSA) which is a convenient alternative to PPA are very similar to those present in PPA. Benzoic acid is also converted into mixed anhydride in P 2 O 5 -MSA.

Indion 190 resin: efficient, environmentally friendly, and reusable catalyst for synthesis of benzimidazoles, benzoxazoles, and benzothiazoles

“…A number of methods are in vogue for the synthesis of these heterocycles by using different catalysts such as Pd-catalyzed oxidative cyclization (12); ionic-liquid-mediated synthesis (13); baseassisted reaction of 1,1-dibromoethanes (14), SiO 2 / ZnCl 2 (15), ZrOCl 2 ×8H 2 O (16), In(OTF) 3 (17), polyethylene-glycol-mediated catalysts (18), and different heteropolyacid catalysts (19), which include condensation of orthoesters 20Á22, nitriles (23), aldehydes (24), carboxylic acids (25), acid chlorides (26), amides (27), and esters (28) with o-substituted aminoaromatics in the presence of different acids or catalysts; Beckmann rearrangement of o-acylphenol oximes (29); photocyclization of phenolic Schiff bases (30); and benzimidazole synthesis in solvent-free conditions (15). More recently, Germin et al (31) have developed cleaner protocols for alkoxybenzimidazole synthesis via S N Ar reaction, and our group developed benzimidazole, benzoxazole, and benzothiazole from condensation of aldehydes with o-substituted aminoaromatics in the presence of phosphorus trichloride (32).…”

Diphosphorus Tetraiodide (P2I4): An Efficient Catalyst for Synthesis of 2-Aryl-1,3-benzazoles via Cyclocondensation of o-Amino/Mercaptan/Hydroxy Anilines with Aryl Acids

“…Recently, substituted alcohols have been used for the synthesis of benzimidazoles and benzothiazoles, however, the use of oxidative steps in case of aldehydes or alcohols affect the overall economy of the reaction [18]. Also, benzoxazoles have been obtained by reacting o-hydroxyphenyl ketoximes with PCl5 or P2O5 and reaction of 2-aminophenols with allenic and acetylenic nitriles [19,20]. However, the above mentioned methods suffer from several disadvantages like harsh reaction conditions (strong acid, high temperature), high catalyst cost, occurrence of side reactions (which leads to poor yield and difficulty in isolation), low reaction rate, additional oxidation step, tedious work-up procedure and lack of selectivity.…”

Synthesis of 2-Aryl Benzoxazoles from Aldoximes

“…The condensation of 2-aminophenol and carboxylic acid 17 or its surrogates such as aldehydes, [18][19][20][21] acid chlorides, [22][23][24] orthoesters, [25][26][27] and β-oxodithioesters 28 under various reaction conditions are the straight forward approaches to construct the benzoxazole unit. However, these methods are often associated with several limitations such as the use of highly toxic reagents, strong acids and, in some cases, harsh reaction conditions.…”