The invention discloses a preparation method of a substituted
cyclobutene compound, which comprises the following specific operations: under the protection of
inert gas, dissolving a compound shown as a formula (I) and a compound shown as a formula (II) in an aprotic
solvent, adding an organic alkali while stirring, controlling the
molar ratio of the compound shown as the formula (I) to the compound shown as the formula (II) to the organic alkali to be 3: 2: 6, and reacting for 2-4 hours; adding an aprotic
solvent, reacting for 2-4 hours at the temperature of 0-60 DEG C, then adding water for
quenching, filtering, washing, and
drying by
distillation under reduced pressure to obtain a product (III), then adding
methanol, then adding NaBH4, and reducing for 6-12 hours, with the
molar ratio of the product (III) to the NaBH4 being 1: 5; and adding water for
quenching, filtering, washing,
drying by
distillation under reduced pressure, and carrying out
column chromatography separation to obtain a product (IV). According to the invention, under the condition of no
metal catalysis, a series of representative substituted
cyclobutene compounds can be obtained through cyclization of a cinnamamide compound
raw material which is simple and easy to obtain and a benzhydryl-3-phenylpropyl-2-
alkyne-1-
imine compound under an alkaline condition.