In 1962, Petro-Tex (now Denka) in the USA was the first company to manufacture maleic anhydride by the oxidation of n-butenes on a commercial scale. After several years, this plant was converted to benzene, and then to , because of pricing. The butenes result as byproducts from the dehydrogenation of butane to butadiene. Today, along with propeneand ethylene, the steam cracking of light gasoline also yields various amounts of unsaturated C₄ hydrocarbons, depending on reaction conditions. After separating the butadiene, which is used elsewhere, the C₄ fraction is oxidixd to maleic anhydride without isolating isobutene, which is totally oxidized. n-Butane remains practically unchanged during thc reaction, just like an inert gas. It is combusted at 800°C along with other off-gas and used for heat generation.

In principle, it is also possible to oxidize butadienc to maleic anhydride. A particular advantage over all previously mentioned feedstocks is that butadicne has the lowest reaction enthalpy, i.e., -237 kcal (-995 k J)/mol compared to e. g., benzene with -447 kcal (-1875 kJ)/mol. However, butadiene is a valuable feedstock for other secondary products and is used preferentially for these.

The catalytic oxidation of a C₄ fraction without butadiene is also carried out using air and a fixed-bed catalyst in a tube reactor. The principle of the process is therefore very similar to that of the benzene process as far as the reaction section is concerned. The basic components of most industrial catalysts are vanadium or phosphoric oxides on carriers with a low surface area, modified with other oxides, e.g., Ti, Mo or Sb. The oxidation takes place at 350-450°C and 2-3 bar with the formation of maleic acid and its anhydride:

The selectivity, relative to the butene content which can be oxidized to maleic anhydride, is usually only 45-60%. The byproducts are CO₂, CO, formaldehyde, and acetic, acrylic, fumaric, crotonic, and glyoxylic acids.

Mitsubishi Chemical uses a V₂O₅-H₃PO₄ catalyst whirled in a fluidized bed for the same oxidation. This technology - used for the first time with maleic anhydride - has the great advantage of more facile heat removal at a uniform reaction temperature. Mitsubishi has used this process in an 18000 tonne-per-year plant since 1970. This plant has since been expanded to 21000 tonnes per year (1995). In contrast to the benzene oxidation, the workup consists merely of washing the reaction gas with dilute aqueous maleic acid solution; i. e., there is no partial condensation of maleic anhydride. The dilute (-40%) maleic acid solution is concentrated either under vacuum or with the help of a water entraining agent (o- or p-xylene). The acid is then dehydrated to the anhydride in a rotary evaporator or a column, either batch or continuous. The maleic anhydride is then separated from lower and higher boiling substances in a two-stage process. The final anhydride is about 99% pure.