A high-level quantum chemistry investigation has been carried out for the abstraction by chlorine atom of hydrogen from methane and five monosubstituted methanes, chosen to reflect the chemical functionalities contained in amino acids and peptides. A modified W1' procedure is used to calculate benchmark barriers and reaction energies for the six reactions. The reactions demonstrate a broad range of barrier heights and reaction energies, which can be rationalized using curve-crossing and molecular orbital theory models. In addition, the performance of a range of computationally less demanding electronic structure methods is assessed for calculating the energy profiles for the six reactions. It is found that the G3X(MP2)-RAD procedure compares best with the W1' benchmark, demonstrating a mean absolute deviation (MAD) from W1' of 2.1 kJ mol(-1). The more economical RMP2/G3XLarge and UB2-PLYP/G3XLarge methods are also shown to perform well, with MADs from W1' of 2.9 and 3.0 kJ mol(-1), respectively.