Since cyclopropanone is highly sensitive, cyclobutanone is the smallest easily handled cyclic ketone.

The Russian chemist Nikolai Kischner first prepared cyclobutanone in a low yield from cyclobutanecarboxylic acid.

[2][3] Kischner's process, involving several steps, is cumbersome and inefficient; more efficient, high-yielding syntheses have since been developed.

A newer, more efficient preparation of cyclobutanone was found by P. Lipp and R. Köster in which a solution of diazomethane in diethyl ether is reacted with ketene.

[6] Another synthesis of cyclobutanone involves lithium iodide catalyzed rearrangement of oxaspiropentane, which is formed by epoxidation of the easily accessible methylenecyclopropane:[7][8] Cyclobutanone can also be prepared in a two step procedure by dialkylation of 1,3-dithiane with 1-bromo-3-chloropropane followed by deprotection to the ketone with mercuric chloride (HgCl2) and cadmium carbonate (CdCO3).