Aliphatic oxime derivatives C7H15CX¼NOH (X = H, CH3, NH2 or OH) have been commercially used ascopper(II) extractants orflotation collectors, but the true nature of their reactivity toward Cu2+ or mineralsurfaces still remains elusive. Using density functional theory (DFT) method, the structure–reactivityrelationship of these aliphatic oxime derivatives was evaluated at B3LYP/6-311 + G(d, p) level. The resultsindicated that the O or N atoms in the head group of octanaldoxime (OTAO), methyl n-heptyl ketoxime(MHKO), N-hydroxyoctanimidamide(HOIM) and n-octanohydroxamic acid (OTHA) are the chemicalreaction center. The reactivity of the aliphatic oxime ionic species increases successively with thereplacement of hydrogen atom by methyl, amino and hydroxyl, suggesting that the affinity of them tocopper species is as follows: OTHA > HOIM > OTAO > MHKO, which coincides with the order of theirbinding energy toward Cu2+. Theflotation performance of aliphatic oxime derivatives to malachite was inthe order of OTHA > OTAO > HOIM > MHKO, which was in line with the combination effect of theirreactivity and hydrophobicity. The established structure–reactivity relationship provides an atomic levelunderstanding of the structural requirements for aliphatic oximes to recover cupric ions or copper oxideminerals.