Cyclobutanone

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.^[4]

One strategy involves degradation of five-carbon building blocks. For example, the oxidative decarboxylation of cyclobutanecarboxylic acid was improved by the use of other reagents and methods.

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.^[5] This reaction is based on a ring expansion of the cyclopropanone intermediate initially formed, wherein molecular nitrogen is split off:

The reaction mechanism was confirmed by a reaction using ¹⁴C-labeled diazomethane.^[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).^[9]

Cyclobutanones are the intermediates of the homo-Favorskii rearrangement, and can be isolated when nucleophiles are absent, as in the synthesis of kelsoene:

At about 350 °C, cyclobutanone decomposes into ethylene and ketene.^[10] The activation energy for this [2+2] cycloelimination is 52 kcal/mol. The reverse reaction, the [2+2] cycloaddition of ketene and ethylene, has never been observed.

Other cyclic ketones:

• Cyclopropanone
• Cyclopentanone
• Cyclohexanone