Polyaluminum chloride (PAC) is an inorganic polymer material that has the advantages of a simple preparation process and special electronic structure. It is considered to be the most efficient and widely used flocculation material for water treatment. In this work, PAC has been used as a Lewis acid catalyst in interdisciplinary fields because of its polynuclear Al–O cation structure. Further, its catalytic mechanism in green organic synthesis has been studied in detail by using the multicomponent Biginelli reaction as the probe. The effect of solvent on the self-assembly and aggregation process of PAC materials was investigated using optical microscopy, UV-Vis spectrophotometry, particle size analysis, XPS, IR, SEM and HR-TEM. The results show that the PAC materials have different morphological characteristics in different solvents. The Al–O–Al cations were transformed in the ethanol solvent to form new multi-nuclear cation aggregates Al_b, which could be used as inorganic micro–nano reactors with unique synergistic catalysis in catalytic reactions. This is the first time the role of PAC in the Biginelli reaction has been analyzed with a liquid in situ infrared instrument, which provided favorable evidence for the speculated reaction mechanism. The PAC–ethanol system is, therefore, considered to be a green, efficient (best yield >99%), economic and recyclable catalyst for catalyzing organic synthesis reactions. The development and utilization of PAC materials in organic synthesis will bring new vitality to this cheap material, which is widely used in industries.