The invention relates to a preparation method of 2, 6-di-tert-butyl p-
cresol, and belongs to the technical field of organic 
chemical synthesis. According to the method, a modified 
mesoporous silica loaded Nb / Mo / Cu three-
metal active center catalyst is used as a catalyst, m-
cresol, p-
cresol and isobutene are mixed to be used as raw materials, 
ultrasonic cavitation is carried out in the catalytic reaction process, and then 2, 6-di-tert-butyl p-cresol is prepared. Mixed cresol is used as a 
raw material, so that a cost is reduced, during preparation of 2, according to the method, m-cresol is separated while 2, 6-di-tert-butyl-p-cresol is separated, by research, it is discovered that the modified 
mesoporous silica loaded Nb / Mo / Cu three-
metal active center catalyst has a synergistic 
catalytic effect of the three-
metal active center, the conversion rate of the mixed cresol and the selectivity of the di-tert-butyl cresol are greatly improved, especially, the selectivity of the 2, 6-di-tert-butyl-p-cresol is improved, impurities such as 2-tert-butyl-p-cresol and 6-tert-butyl-m-cresol are reduced, meanwhile, under the action of 
ultrasonic cavitation, a liquid-gas reaction is promoted to forma 
microreactor in micropores in a 
solid catalyst, the catalytic activity is greatly improved, the gas-liquid two-phase 
mass transfer efficiency and 
heat transfer area are increased, and the conversion rate of raw materials is further increased.