The Synthetic Intermediate of Pyridoxine. II. The Thermal Cyclization of Ethyl α-Isocyanopropionate to 5-Ethoxy-4-methyloxazole

Abstract

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.

Exploiting the Divergent Reactivity of α‐Isocyanoacetate: Multicomponent Synthesis of 5‐Alkoxyoxazoles and Related Heterocycles

“…Addition of lithium bromide (1 equiv) provided 10 a in lower yield due to undesired ring-chain tautomerization of isocyanide 8 a, which led to the 2-unsubstituted oxazole. [23] The same reaction proceeded smoothly in MeOH to afford 10 a in 90 % yield. The reaction performed in DMSO produced compound 10 a but with a much-reduced yield.…”

Sesquiterpene lactones of Eupatorium recurvans

“…Characterization of the Lactones. Lactone la, wt 16 Other important mass spectral peaks were at m/e 363 (M+ -C9H3O,), 321 (M+ -C6H902), 261 (M+ -C2H302 -C6Hi0O2), and 243 (M+ -C2H3G2 -C5H10O2 -H20).…”

Synthesis of [13C3]-B6 Vitamers Labelled at Three Consecutive Positions Starting from [13C3]-Propionic Acid

“…This is probably due to, inter alia, the resulting lower volatility of the product and, therefore, presumably lower losses during the isolation of the product. While the preparation of these oxazoles (e.g., 5-butoxy-oxazole) was reported starting from other substrates such as n -butyl α-isocyanopropionate or 1-bromo-1- n -butoxyacetone, the influence of the alkoxy chain on this specific cyclisation procedure using P 2 O 5 has not been documented in the literature yet [ 38 , 42 ]. The labelled oxazole 10 was finally prepared using the optimized reaction conditions and verified via ESI-MS ([(M + H) + ] m/z = 159.1, 62%, Table 3 , entry 9).…”

“…A revolutionizing step enabling industrial scale production of PN involved the incorporation of Diels-Alder reactions into the synthetic route through condensation of 4,5-substituted-oxazoles and diverse ene-substrates in order to synthesize pyridine-based structures [ 34 , 35 , 36 , 37 , 38 ] ( Scheme 3 ).…”