PHAR1110
Acidity and Basicity
Exercise
Q. Arrange the following phenol derivatives in order of increasing acidity.
Explain your answer briefly. (4 marks)
To answer this Q, you need to know the e- donating or e- withdrawing effect of
the different substituents attaching to phenol
(this will be taught in a later topic of this course)
Please find a table below showing common e- donating versus e- withdrawing groups
EDG = e- donating gp EWG = e- withdrawing gp
EDG can be recognized EWG can be recognized either
by lone pairs on the atom by the atom adjacent to the
adjacent to the system system having several bonds
e.g. -OCH3 to more electronegative atoms
or having a formal +ve or +ve
except –R, -Ar, or –viny More e donating charge, e.g. -CO2R, -NO2
(hyperconjugation, e-)
EWG remove e- density from
EDG add e- density to the the system, making it less
system, making it more nucleophilic
nucleophilic
More e withdrawing
Ka
HA H+ + A-
• The more stable conjugate base (i.e., A-) formed, the
stronger the acid will be.
• Key consideration:
- “localized charge” is not good for stability
- Therefore, any substituent that can help “neutralize” or
“disperse” the charge will produce a more stable
conjugate base
- e- withdrawing group attaching to phenol can increase
the stability of the phenoxide formed
Acidity ranking: 4 5 3 1 2
(1 – most acidic 5 – least acidic)
• Both Cl and NO2 are e- withdrawing groups (NO2 being more e- withdrawing)
• Methoxy group (or alkoxy functional group) is e donating
• When NO2 is para to OH, the anion stabilizing effect is greater than when NO2
is meta to OH
Q. Arrange the following compounds in order of increasing acidity.
(i) CH3CO2H
(ii) CH3COH
(iii) CCl3CO2H
(iv) CH3CH2OH
(v) CH3CH2SH
Explain your answer. (5 marks)
Increasing ranking of acidity:
(ii) < (iv) < (v) < (i) < (iii)
• Resonance stabilization in carboxylate makes carboxylic acid more acidic than other
compounds in the list
• In (iii), the e- withdrawing group (Cl) increases the acidity further because Cl help
“neutralize” the –ve charge on the carboxylate
• Thiols (-SH) are more acidic than alcohols (-OH) due to weaker X-H bond
(S is bigger than O)
• Aldehydes are less acidic than alcohols (sp2 hybridization of C in aldehyde holds
the H tighter) sp3 hybridization
sp2 hybridization
Q. Disopyramide is an antiarrhythmic drug, which is used to correct abnormal rhythms
of the heart. There are three nitrogens in the structure of disopyramide.
Rank these nitrogens in the correct order of basicity.
Explain the rank order. (3 marks)
#3 is the most basic
In (3), the three alkyl groups donate e- to the N, making
(1) the e density very rich and readily available.
.. .. CH
sp2 N In (1), the lone pair is located in the sp2 hybrid orbital.
H2N 3 Therefore, the lone pair is not delocalized to the e cloud
(2) O sp3
in the aromatic ring. Thus these e- are available.
N CH3
(3)
However, aromatic N has sp2 hybridization whereas
H3C CH3 aliphatic N has sp3 hybridization.
The higher “s” character in sp2 N makes the lone pair
less available compared to aliphatic sp3 N (s is spherical
in shape and therefore more attracted to the nucleus)
In (2), the lone pair on N is delocalized to the adjacent carbonyl functional group,
making them less available. Therefore #2 is the least basic.
