Abstract The formation of acetone from 2-propanol and Rh(111)-p(2 × 1)-O has been investigated by temperature programmed reaction and X-ray photoelectron spectroscopies and isotopic labeling experiments under ultrahigh vacuum conditions. Some 2-propanol forms 2-propoxide on Rh(111)-p(2× 1)-O below 250 K and selective β (with respect to the metal in 2-propoxide) C-H bond breaking at ∼ 270 K is the primary path for acetone evolution. A minor amount of reversible C-H bond activation is also observed. β-carbon-hydrogen bond breaking is proposed to be the rate-limiting step for the initial acetone evolution from 2-propanol on Rh(111)-p(2× 1)-O at high coverage based on kinetic isotope effects. The rate of acetone evolution is in part rate-limited by desorption, however, for low 2-propanol exposures. In addition, there is some oxygen exchange between the surface and the acetone at ∼ 320 K. Combustion to H 2O, CO and CO 2 is a competing pathway. Irreversible γ-C-H bond breaking primarily leads to combustion. The reactivity of 2-propanol on the (2 × 1)-O surface is dramatically different from that on clean Rh(111), where nonselective decomposition to CO and H 2 is induced. The inhibition of extensive, nonselective C-H and C-C bond breaking is a crucial factor in determining the selectivity for β-dehydrogenation to produce acetone.