Optimization of Synthetic Strategy of 4′4″(5″)-Di-tert-butyldibenzo-18-crown-6 Using Response Surface Methodology

4′,4″(5″)-Di- tert -butyldibenzo-18-crown-6 (DTBB18C6) was synthesized using 4- tert -butyl catechol (TBC) as starting material, 2,2′-diethylene glycol di( p -touenesulfonate) as cyclization reagent, Cs 2 CO 3 as template, and tetrahydrofuran (THF) as solvent. The reaction was carried out in a sealed environment with nitrogen, and Cs 2 CO 3 was supplemented in three steps. Response surface methodology (RSM) was used to investigate the effects of reaction temperature ( X 1 ), initial concentration of TBC ( X 2 ), reaction time ( X 3 ), and Cs 2 CO 3 /TBC molar ratio ( X 4 ); the experiment method was compared with published methods. From the result of RSM, the operation conditions for maximum yield, such as reaction temperature, reaction time, initial concentration of TBC, and Cs 2 CO 3 /TBC molar ratio were found to be 49.15 °C, 72 h, 0.06 mol/L and 3.22, respectively. Under these optimum conditions, DTBB18C6 yield ( Y ) reached 43.38%.