S1 Supporting Information Searching for computational strategies to accurately predict pKas of large phenolic derivatives Aida Mariana Rebollar-Zepeda, Tania Campos-Hernández, María Teresa Ramírez-Silva, Alberto Rojas-Hernández, Annia Galano  Departamento de Química, División de Ciencias Básicas e Ingeniería. Universidad Autónoma Metropolitana-Iztapalapa, Av San Rafael Atlixco No.186, Col.Vicentina C.P.09340, México D.F. Table of Contents Table 1S. CO distance (Å) in the phenoxide anions............................................................................. 2 Table 2S. Calculated values of the pKa of acetaminophen. ................................................................ 5 Table 3S. Calculated values of the pKa of profadol............................................................................. 6 Table 4S. Calculated values of the pKa of tapentadol......................................................................... 7 Table 5S. Calculated values of the pKa of ketobemidone................................................................... 8 Table 6S. Calculated values of the pKa of 3‐methoxyphenol (m‐OCH 3 ). ............................................ 9 Table 7S. Calculated values of the pKa of 4‐methylphenol (p‐CH 3 ). ................................................. 10 Table 8S. Calculated values of the pKa of 3‐cyanophenol (m‐CN).................................................... 11 Table 9S. Calculated values of the pKa of 4‐methylthiophenol (p‐SCH 3 ).......................................... 12 Table 10S. Calculated values of the pKa of 3‐hydroxybenzaldehyde (m‐CHO)................................. 13 Table 11S. Calculated values of the pKa of 2,4‐dimethylphenol (op‐2CH 3 ). ..................................... 14  To whom correspondence should be addressed. E-mail: agalano@xanum.uam.mx