Convenient One-Pot Synthesis of 2-Oxazolines from Carboxylic Acids

Simple one-pot methods for preparation of 2-oxazolines have been developed using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). Treatment of a mixture of carboxylic acids and 2-haloethylammonium salts with DMT-MM in methanol followed by refluxing in the presence of KOH gives oxazolines. Preparation of 2-oxazoline, a versatile intermediate in synthetic chemistry, from carboxylic acids is a classical and useful method.1-5) Since 2-oxazolines can be readily re-converted into carboxylic acids, they can be used as a protecting group for carboxylic acids.3,6) Among various methods employed to convert derivatives of carboxylic acids to the oxazolines, intramolecular dehydrohalogenation of N-(β-haloethyl)amides to give 2-oxazolines is well established.1,4,5,7) Although the reaction readily takes place by treatment with either base or silver ion, such reactions have not adapted well to the preparation of 2-oxazolines, presumably because of the cumbersome method used to prepare N-(β-haloethyl)amides.