Why is the pKa of the thiol group in N-acetylcysteine higher then the pKa of the thiol group in cysteine?
Shown below are the relevant ionization events of cysteine and N-acetylcysteine. The question is asking about the second ionization of each, the deprotonation of the thiol groups, but we see a similar difference in pKas for the carboxylic acid groups as well. The difference in each case is an ammonium group vs. an acylated nitrogen. It's true that the acetyl group is an electron withdrawing group, but it turns out that the cationic ammonium group is even more inductively electron withdrawing. For both the first and second ionizations, the difference in electron withdrawing power is enough to lower the pKa by >1 pKa unit.



iad22agp's explanation is a good way of rationalizing this. Looking at the first ionization, cysteine is cationic while N-acetyl cysteine is neutral. Since the rest of the structures are similar, we would assume that it's easier to take a positive charge away from a positively charged compound than a neutral compound. Similarly looking at the second ionization, it's easier to take a positive charge away from a neutral compound than a compound that's already negatively charged.

pKa refs: cysteine, N-acetylcysteine