Finally, the initial hypothesis that halogenating agents based upon an anomeric amide backbone would exhibit superior reactivity was evaluated computationally (Figure ). Although anomeric amide chlorinating reagent and Palau'chlor have the same N-Cl bond length (both 1.73 Å, longer than 1.66 Å for TCCA and 1.69 Å for NCS ), the conversion of 14 to 14-Cl is calculated to be more energetically favorable by a factor of 10 ^2.7 (ΔΔG = -3.75 kcal/mol) using 6 (Figure ), which is in accord with experimental findings. To gain deeper insight into this higher reactivity, DFT calculations of the N-Cl bond breaking energy (from the ground state to the corresponding anion and Cl + ) for both reagents was performed. Calculations indicate that this bond breaking event is significantly uphill for both reagents, but reagent 6 requires 25 kcal/mol less energy for bond breaking than Palau'chlor, which means 6 has a more active N-Cl bond (Figure ). In the case of reagent 6, when Palau'chlor: 0% TCCA: 73% roflumilast(35)-X X = Cl, 91% (1.54 g, 95%)