12-Crown-4 can be synthesized using a modified Williamson ether synthesis, using LiClO as a templating cation:
: (CHOCHCHCl) + (CHOH) + 2 NaOH → (CHCHO) + 2 NaCl + 2 HO
It also forms from the cyclic oligomerization of ethylene oxide in the presence of gaseous boron trifluoride.