# pKa values for protonated nitrogens in ketoconazole

Everywhere on the internet I see that the two $\mathrm pK_\mathrm a$'s of ketoconazole are 6.4 and 2.3, but I don't think that is correct.

The $\mathrm pK_\mathrm a$ of imidazole is around 6.4 . But ketoconazole also has a piperazine ring and normally this $\mathrm pK_\mathrm a$ is around 9.8. There are electron acceptors but I still find 2.3 to be very low. Is this correct and which of the two nitrogens will be protonated?

• Can you provide references for the values you're seeing everywhere on the internet? Here is a 2-year old presentation from UCB Celltech in which the p$K_{\rm a}$ values for ketoconazole are given as 6.43 and 3.64. – Todd Minehardt Aug 18 '15 at 20:19