The thermal cyclization of ethyl α-isocyanopropionate (I) was performed to 5-ethoxy-4-methyloxazole (II) as an intermediate for the synthesis of pyridoxine. The similar reaction of several new alkyl esters of α-isocyanocarboxylic acid to the corresponding 5-alkoxy-4-substituted oxazole was also carried out. The reaction products of the thermal cyclization of I were investigated. When the cyclization was carried out at 180°C for 5 hr, the maximum yield of the main product, II, was 20%; unreacted I (30%), ethyl α-cyanopropionate(20%), and dimer of I (5%) were also obtained. The α-hydrogen of ethyl α-isocyanosuccinate (X) can be more easily removed than that of I, so X may be expected to be more readily converted to 5-ethoxy-4-ethoxycarbonylmethyloxazole (XI), which is also an intermediate of pyridoxine. The yield of XI from X did not exceed 30% because of the side reaction.
I. Maeda, K. Togo, R. Yoshida
Bulletin of the Chemical Society of Japan