Ethyl cyanohydroxyiminoacetate Ethyl cyanohydroxyiminoacetate Ethyl cyanohydroxyiminoacetate (oxyma) is the oxime of ethyl cyanoacetate and finds use as an additive for carbodiimides, such as dicyclohexylcarbodiimide (DCC) in peptide synthesis. It acts as a neutralizing reagent for the basicity or nucleophilicity of the DCC due to its pronounced acidity (pKa 4.60) and suppresses base catalyzed side reactions, in particular racemization. Ethyl cyanohydroxyiminoacetate is obtained in the reaction of ethyl cyanoacetate and nitrous acid (from sodium nitrite and acetic acid) in 87% yield. Because of the rapid hydrolysis of the ester, the reaction should be carried out at pH 4.5, in buffered phosphoric acid the
2-Ethyl-2-oxazoline one-pot reaction propionic acid is converted first with 2-aminoethanol to 2-hydroxyethylamide, than reacted with boric acid at 130 °C yielding a boric acid ester which is finally thermolyzed at 280 °C in 92% yield to 2-ethyl-2-oxazoline. From propionic acid and thionyl chloride can be obtained propanoyl chloride, which reacts with ethanolamine in the presence of an acid scavenger (for example pyridine) to N-propionyl-2-aminoethanol. With further thionyl chloride this reacts further to 2-chloroethylamide. With the chloride ion as a better leaving group, this intermediate is cyclized by simple heating to the oxazoline. Water must be excluded du to the tendency of