Method for producing 2-amino-5-substituted-1,3,4-oxadiazole

A method for producing a 2-amino-5-substituted-1,3,4-oxadiazole, the method comprising

• (A) a step of preparing a cyanogen chloride solution from hydrogen cyanide and chlorine,
• (B) adjusting an amount of hydrochloric acid, which is a byproduct produced together with cyanogen chloride in (A), to 0.5 equivalents or less relative to the cyanogen chloride produced,
• (C) subjecting a carboxylic acid hydrazide represented by formula (1) and the cyanogen chloride solution to a reaction to produce a solution containing a 2-amino-5-substituted-1,3,4-oxadiazole hydrochloride represented by formula (2):
• wherein R is a hydrogen atom or a group selected from the group consisting of a C1 to C6 alkyl group, an aryl group, a 5- or 6-membered aromatic heterocyclic group, and an alkoxy group and optionally substituted with a halogen atom or a C1 to C4 alkyl group,
• wherein R is a hydrogen atom or a group selected from the group consisting of a C1 to C6 alkyl group, an aryl group, a 5- or 6-membered aromatic heterocyclic group, and an alkoxy group and optionally substituted with a halogen atom or a C1 to C4 alkyl group,
• (D) adding, to the solution obtained in (C), a base in an amount that is equal to or more than an equivalent obtained by adding up an amount of cyanogen chloride and an amount of the byproduct hydrochloric acid in the cyanogen chloride solution used in (C), and
• (E) cooling a solution containing a hydrochloride of the base obtained in (D) and separating a precipitated crystal to thereby obtain the 2-amino-5-substituted-1,3,4-oxadiazole represented by formula (3):
• wherein R is a hydrogen atom or a group selected from the group consisting of a C1 to C6 alkyl group, an aryl group, a 5- or 6-membered aromatic heterocyclic group, and an alkoxy group and optionally substituted with a halogen atom or a C1 to C4 alkyl group.