Partial pKₐ data for a homologous series of acetic-acid derivatives are collected at 298 K:
Acid
Structural formula
pKₐ
Acetic acid
CH₃COOH
4.76
Chloroacetic acid
CH₂ClCOOH
2.86
Dichloroacetic acid
CHCl₂COOH
1.29
Trichloroacetic acid
CCl₃COOH
0.65
A chemist now synthesizes 2-chloro-2-methoxyacetic acid, ClCH(OCH₃)COOH (Compound E), which contains both a chlorine and a methoxy group attached to the α-carbon.
(a) Using the data in the table, estimate the individual contribution of one chlorine substituent to the change in pKₐ relative to acetic acid. Assume the effect is approximately additive for the first two chlorines.
(b) The methoxy group donates electron density by resonance but withdraws by induction. Using qualitative reasoning, decide whether the net effect of the methoxy group on the conjugate base of Compound E will increase or decrease the acid strength relative to chloroacetic acid. Explain your answer.
(c) Combine your results from parts (a) and (b) to predict an approximate pKₐ range (±0.5 pKₐ units) for Compound E. Provide a clear justification that addresses both substituents simultaneously.
(d) Discuss one limitation of treating substituent effects as strictly additive when more than one electron-donating or electron-withdrawing group is present on the same carbon.