Quinone methides (QMs) are formed as the intermediates during lignin biosynthesis and chemical transformation; the chemical structure of the resulting lignin can then be significantly modified via the corresponding aromatization. Herein, the structure-reactivity relationship of β-O-4-aryl ether QMs (GS-QM, GG-QM and GH-QM, which are 3-monomethoxylated QMs carrying syringyl, guaiacyl and p -hydroxyphenyl β-etherified aromatic rings, respectively) was investigated to clarify the formation of alkyl-O-alkyl ether structures in lignin. The structural features of these QMs were characterized by NMR spectroscopy, and their alcohol-addition experiment was well performed at 25 °C to generate alkyl-O-alkyl/β-O-4 products. The preferential conformation of GS-QM contains a stable directional intramolecular H-bond between γ-OH hydrogen and β-phenoxy oxygen, which makes the β-phenoxy group locate on the same side with γ-OH. In contrast, the β-phenoxy groups in both GG- and GH-QM conformations are distant from the γ-OH; thus, the stable intermolecular H-bond is associated with the γ-OH hydrogen. Based on UV spectroscopy, the addition of methanol and ethanol occurs in QMs with a half-life of 1.7-2.1 and 12.8-19.3 minutes, respectively. With the same nucleophile, these QMs react faster in the order GH-QM > GG-QM > GS-QM. However, the reaction rate appears to be more influenced by the type of nucleophile than by the β-etherified aromatic ring. Furthermore, the NMR spectra of products indicate that the steric bulkiness of both the β-etherified aromatic ring and nucleophile contributes to the erythro -preferential formation of adducts from QMs. Moreover, the effect is more pronounced for the β-etherified aromatic ring of QMs than the nucleophiles. The structure-reactivity relationship study demonstrates that the competition effect between H-bonds and steric hindrance determines the approaching direction and the accessibility of nucleophiles to planar QMs, resulting in stereo-differentiating formation of adducts. This model experiment may provide implications for the biosynthetic route and structural information of the alkyl-O-alkyl ether structure in lignin. Its results can also be further utilized to design innovative extraction methods of organosolv lignins for subsequent selective depolymerization or material preparation.