Chapter 8:

Organic Acids and Bases

 Acid/Base Reactions
• Some organic chemicals have exchangeable
protons (acids) or lone pair electrons which can
accept hydrogen (bases)
• Ionized form of these compounds acts very
differently from the neutral form (different HLC,
Kow, etc)
• Proton transfer reactions are usually very fast and
reversible, so we can treat them as an equilibrium
process
Acidity Constant

Organic acids:
HA + H2O  H3O+ + A-

choosing pure water as a reference state:

H+ + H2O  H3O+

by convention, G  = 0, K = 1
Thus,
HA  H+ + A- ; lnKa = -(G /RT)
At equilibrium:

ln Ka  ln
     
 'H  H    'A A 

G o

 HA   HA
 '
RT
Ka = acid dissociation constant
 typically measure activity of H+, and conc of HA, A-
(mixed acidity constant)
 at low ionic strength,   1

ln Ka  ln
  
H  A
 HA
log
 A 


 log K  pH  pH  pKa
 HA a

when pH = pKa, [A-] = [HA]

For organic bases, treatment is similar:
B + H2O  BH+ + OH-

Kb 
  
 'OH  OH   'BH  BH   
 B  B 
 '

written as acidity constant:

BH+  B + H+

   H     B  
'  '
 H B
Ka
  BH 
'
BH 


pKa + pKb = pKw = 14 at 25C

Ka * Kb = Kw = 10-14 at 25C
carboxylic acids amines

acids

phenols bases

heterocycles with N
Important functional groups:
Acids: Bases:
CH3-OH alcohols NH3 ammonia
(pKa > 14) (pKa = 9.25)
O
Carboxylic acids CH3NH2 primary amine
CH3-C-OH (pKa = 4.75) (pKa = 10.66)
(CH3)2NH secondary amine
Phenols (pKa = 9.82) (pKa = 10.73)
(CH3)3N tertiary amine
(pKa = 9.81)
benzoic acids (pKa = 4.19)
anilines (pKa = 4.63)

N pyridines (pKa = 5.42)

 Temperature effect on pKa
recall that the effect of temperature on any
equilibrium constant:
K ia T 2  r H 0  1 1 
ln    
K ia T 1 R  T1 T2 
for strong acids, rHo is very small
rHo increases as pKa increases (weaker acids have higher
temperature dependence) (Why?)

hmmm… what is the rS of a proton transfer reaction?

 Speciation in natural waters
Q: Does the presence of an organic acid affect the pH of the
water?
A: Probably not. Why?
Natural waters are usually buffered by carbonate (among
other things).
If carbonate is present at 10-3 M and the pH is neutral, then
addition of acid at 10-5 M (a factor of 100 less than the buffer)
will have virtually no effect on pH.
 Speciation in natural waters
fraction of acid in the neutral form:


 HA 

1

1
 HA    A  1  [ A ] 1  10
  ( pH  pK a )

[ HA]

fraction of base in the neutral form:

1
 Chemical structure and pKa
We are mostly concerned with compounds for which
3 < pKa <11
aliphatic and aromatic carboxyl groups
aromatic hydroxyl groups (phenols)
aliphatic and aromatic amino groups
N heterocycles
aliphatic or aromatic thiols
These classes of compounds have pKa’s which vary widely
Why?
Substituents can have a dramatic effect on the pKa of
the compound
Substituent effects are of three types:

Inductive effects
positive (electron donating) for O-, NH-, alkyl
negative (electron withdrawing) for NO2, halogen, ether,
phenyl, etc.
Delocalization effects (resonance)
positive for halogen, NH2, OH, OR
negative for NO2, others
Proximity effects
intramolecular hydrogen bonding
steric effects
Inductive effects

pKa
alkyl groups
acetic acid 4.75
are weakly
propanoic acid 4.87 electron
donating
butyric acid 4.85
4-chlorobutyric acid 4.52 chlorines are
strongly
3-chlorobutyric acid 4.05
electron
2-chlorobutyric acid 2.86 withdrawing

proximity is crucial
 Delocalization effects (resonance)
positive for halogen, NH2, OH, OR
negative for NO2, others

Example:
chlorinated phenols: general reduction in
pKa due to chlorine
phenol 9.92
substitution is caused
2-chlorophenol 8.44 by inductive (electron
3-chlorophenol 8.98 withdrawing effect)
4-chlorophenol 9.29
specific reduction in
2.4-dichlorophenol 7.85 pKa (dependent on
2,4,5-trichlorophenol 6.91 chlorine position) is
2,4,6-trichlorophenol 6.19 caused by resonance
2,3,4,5-tetrachlorophenol 6.35 effect
2,3,4,6-tetrachlorophenol 5.40
pentachlorophenol 4.83
Resonance effect of hydroxyl and amino
groups
Resonance effects are heavily influenced by
position
Proximity effects
highly specific interactions due to proximity of
substituents to the functional group:
often difficult to quantify

intramolecular hydrogen bonding

steric effects
examples
 Predicting acidity constant
For some specific aromatic structures, acidity constant
can be estimated via:

Hammett Correlation
effects of substituents are quantified via  values

pKa  pKaH     i
i

the pKa of the unknown = the pKa of the unsubstituted parent

structure minus the susceptibility factor times the sum of all
the Hammett constants
sigma
rho
Due to promixity (steric) effects, influence of ortho substituents
is hard to quantify.
The same substituent in the ortho position may have a different
effect on pKa for different acids.
Hammett constants can be used to
predict properties other than pKa

Specifically, rate constants for hydrolysis (chapter 13)

Also, redox potential?
 Chlorobenzenes: Hammett constants
Cl (ortho) R2 -50
exptl 2.01 0.63
bond 1.23 0.90 -70
comp 1.17 0.99
-90
H2
Cl (meta) = 0.37
-110
Cl (para) = 0.23
-130
Exptl without
trichlorobenzenes: -150
Cl (ortho) = 1.53 0 1 2 3 4 5
R2 = 0.985 Ss
 Taft correlation
pK a  pK a CH 3        Es
* *

Similar to Hammett correlation, but applicable to aliphatic

systems.
Reference compound has methyl group at the position of the
substituent.
Influence of substituent on pKa is divided into polar
(electronic) and steric effects.
* = polar substitutent constant
* = susceptibility of backbone to polar effects
Es = steric substituent constant
 = susceptibility of backbone to steric effects
also used to predict reactivity . . . see Chapter 13
Partitioning Behavior of Organic Acids and Bases
pH dependence of solubility: speciation
Solubility is the equilibrium
partitioning of a compound between
HA  H+ + A-
the pure liquid phase and water.
The solubility and activity coefficient
of HA (the neutral form) depends on
HA (pure
its size, polarity, and H-bonding
liquid or solid) ability.
The intrinisic solubility of HA is not
affected by acid-base reactions.
However, the apparent solubility is
highly dependent on pH due to
protonation. the charged species has a
much higher solubility than the neutral
form.
 represents the fraction 
 HA
of the total amount of  HA   A  
the compound that is in
the neutral form. 1

1  10 pH  pKa
To determine the total
solubility of an
ionizable compound, Cwsat, HA
Cwsat,tot 
first determine the 
solubility of the neutral
form, then determine  similarly, for B:
at the given pH. Cwsat,B
Cwsat,tot 
1
 Henry's Law (air-water partitioning):

Assume that the ionized form cannot volatilize (no ionized

gases allowed!)
Only the neutral species is avialable for air/water exchange
KH

Daw HA, A 
  K  
'
H
RT
For base:

KH

Daw B , BH 
  1   K  1  
'
H
RT
 Octanol-water partitioning:

ionized form can partition into octanol by itself or

as an ion pair
observations suggest Kow (HA)  100 Kow (A-)

so, by analogy to KH:


Kow HA, A   K  HA

ow

Kow  B, BH    1    K  B

ow
 Problem 8-1
Represent graphically the speciation of 4-methyl-2,5-
dinitrophenol and 3,4,5-trimethylaniline, and 3,4-
dihydroxybenzoic acid as a function of pH (2-12).
Estimate (if necessary) the pKa values of the
compounds.
 Problem 8.2

Represent graphically the approximate fraction of (a) total

2,3,4,6-tetrachlorophenol and (b) total aniline present in the
water phase of a dense fog (air-water volume ratio ~105) as
a function of pH (pH range 2 to 7) at 5 and 25C. Neglect
adsorption to the surface of the fog droplet. Assume and
awHi value of about 70 kJ/mol for TCP and 50 kJ/mol for
aniline. All other data can be found in Appendix C.