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 = 1Thus, HA H+ + A- ; lnKa = -(G /RT)

ln ln' '

'K

H A

HA

G

RTa

H A

HA

o

At equilibrium:

Ka = acid dissociation constant

typically measure activity of H+, and conc of HA, A- (mixed acidity constant)

at low ionic strength, 1

ln lnKH A

HAa

log logA

HAK pH pH pKa a

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

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

K

OH BH

Bb

OH BH

B

' '

'

written as acidity constant:BH+ B + H+

BH

BHK

BH

BHa '

''

pKa + pKb = pKw = 14 at 25C

Ka * Kb = Kw = 10-14 at 25C

acids

bases

carboxylic acids

phenols

amines

heterocycles with N

O

Important functional groups:Acids:

CH3-OH alcohols (pKa > 14)

Carboxylic acids (pKa = 4.75)CH3-C-OH

Phenols (pKa = 9.82)

benzoic acids (pKa = 4.19)

Bases:

NH3 ammonia (pKa = 9.25)

CH3NH2 primary amine (pKa = 10.66)

(CH3)2NH secondary amine (pKa = 10.73)

(CH3)3N tertiary amine (pKa = 9.81)

anilines (pKa = 4.63)

pyridines (pKa = 5.42)N

Temperature effect on pKa

21

0

1

2 11ln

TTR

H

K

K r

Tia

Tia

recall that the effect of temperature on any equilibrium constant:

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 watersQ: 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

)(101

1

][][

1

1apKpH

HAAAHA

HA

fraction of acid in the neutral form:

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 groupsaromatic hydroxyl groups (phenols)aliphatic and aromatic amino groupsN heterocyclesaliphatic or aromatic thiols

These classes of compounds have pKa’s which vary widelyWhy?

Substituent effects are of three types:

Inductive effectspositive (electron donating) for O-, NH-, alkylnegative (electron withdrawing) for NO2, halogen, ether, phenyl, etc.

Delocalization effects (resonance)positive for halogen, NH2, OH, ORnegative for NO2, others

Proximity effects intramolecular hydrogen bondingsteric effects

Substituents can have a dramatic effect on the pKa of the compound

Inductive effects

pKa

acetic acid 4.75

propanoic acid 4.87

butyric acid 4.85

4-chlorobutyric acid 4.52

3-chlorobutyric acid 4.05

2-chlorobutyric acid 2.86

alkyl groups are weakly electron donating

chlorines are strongly electron withdrawing

proximity is crucial

Delocalization effects (resonance)positive for halogen, NH2, OH, ORnegative for NO2, others

Example:chlorinated phenols:

phenol 9.922-chlorophenol 8.443-chlorophenol 8.984-chlorophenol 9.292.4-dichlorophenol 7.852,4,5-trichlorophenol 6.912,4,6-trichlorophenol 6.192,3,4,5-tetrachlorophenol 6.352,3,4,6-tetrachlorophenol 5.40pentachlorophenol 4.83

general reduction in pKa due to chlorine substitution is caused by inductive (electron withdrawing effect)

specific reduction in pKa (dependent on chlorine position) is caused by resonance effect

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 bondingsteric effects

examples

Predicting acidity constant

For some specific aromatic structures, acidity constant can be estimated via:

Hammett Correlationeffects of substituents are quantified via values

pK pKa aH ii

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?

-150

-130

-110

-90

-70

-50

0 1 2 3 4 5S

H2

Chlorobenzenes: Hammett constants

Cl (meta) = 0.37

Cl (para) = 0.23

Exptl without trichlorobenzenes:

Cl (ortho) = 1.53

R2 = 0.985

Cl (ortho) R2

exptl 2.01 0.63bond 1.23 0.90comp 1.17 0.99

Taft correlationsCHaa EpKpK **

3

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 BasespH dependence of solubility: speciation

HA H+ + A-

HA (pure liquid or solid)

Solubility is the equilibrium partitioning of a compound between the pure liquid phase and water.

The solubility and activity coefficient of HA (the neutral form) depends on its size, polarity, and H-bonding 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.

HA

HA A

1

1 10pH pKa

CC

w totsat w HA

sat

,,

1,

,

satBwsat

totw

CC

similarly, for B:

represents the fraction of the total amount of the compound that is in the neutral form.

To determine the total solubility of an ionizable compound, first determine the solubility of the neutral form, then determine at the given pH.

Assume that the ionized form cannot volatilize (no ionized gases allowed!)Only the neutral species is avialable for air/water exchange

D HA A KK

RTaw HH, '

D B BH KK

RTaw HH, ' 1 1

For base:

Henry's Law (air-water partitioning):

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:

K HA A K HAow ow,

K B BH K Bow ow, 1

Problem 8-1Represent 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.