East West University

Non-aqueous Acid-Base
Titration
PHRM-309

Tareq Hasan
 Table of Contents

NON – AQUEOUS ACID – BASE TITRATION..............2

INTRODUCTION.........................................................2
Reasons for Performing Non – Aqueous Acid – Base Titration 2
Interaction of H2O with the Titrant......................2
Poor Solubility of Weak Acids (WA) or Weak Bases (WB) in H2O 3
DIFFERENT ACID – BASE THEORY..................................3
Arrhenius’s Acid – Base Theory.........................3
Limitations of Arrhenius’s Acid – Base Theory.....3
Bronsted – Lowry Theory of Acid – Base...........4
Advantages of Bronsted – Lowry Theory of Acid – Base 4
Limitations of Bronsted – Lowry Theory of Acid – Base 5
Lewis’ Theory of Acid – Base.............................5
Advantages of Lewis’ Concept of Acid – Base......6
STRENGTH OF ACID & BASE........................................6
Strength of Acid.................................................6
Explanation for a Strong Acid (SA).........................6
Explanation for a Weak Acid (WA)........................7
SOLVENTS USED IN NON – AQUEOUS ACID – BASE TITRATION 7
Protophillic Solvent...........................................7
Protogenic Solvent............................................8
Amphiprotic Solvents........................................9
Aprotic Solvents..............................................10
Reasons for using Aprotic Solvents....................10
THEORY OF NON – AQUEOUS ACID – BASE TITRATION...10
Titration of Weak Acid (WA)............................11
Theory................................................................11
Apparatus for Controlled Environment..............12
Burette for protecting the Titrant..................12
Analytical / Titration Vessel for Analysis........12
Practical Example...............................................12
Titration of Weak Base (WB)...........................14
Theory................................................................14
Practical Example – 1.........................................15

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Practical Example – 2.........................................16

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Non – Aqueous Acid – Base 1. Interaction of the Titrant with H 2O
Titration 2. Poor Solubility of Weakly Acidic (W A) or
Introduction Weakly Basic (WB) Analyte in H2O

 A Non – Aqueous Acid – Base Titration Interaction of H 2 O with the Titrant

involves the titration by neutralization of
 In the aqueous titration of a Weakly
either acid or base by their opposite entities
Acidic / Weakly Basic Analyte by a
in a non – aqueous medium.
Strongly Basic / Strongly Acidic Titrant
Reasons for Performing Non – respectively, the solvent also reacts
Aqueous Acid – Base Titration with the titrant, because of having both
Weakly Acidic and Weakly Basic
 Non – aqueous Acid – Base Titration is
properties.
performed to eliminate 2 problems
 As a result –
encountered during the aqueous titration of
 More titrant will be required
weakly acidic or weakly basic analyte by a
 Detected end – point will give
Strong Acid or Strong Base Titrant
wrong result or no end – point will
respectively.
occur
 The 2 problems are –

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Figure 1: Reacti on of Water with ti trants in Aqueous Titrati on of Weak Acid or Weak Acid

Poor Solubility of Weak Acids (W A )  Broadly, acid – base theories are classified
or Weak Bases (W B ) in H 2 O into –

 Most of the WA or WB Analytes are – 1. Arrhenius’s Acid – Base Theory

 Non – Polar 2. Bronsted – Lowry Theory of Acid – Base

 Organic 3. Lewis’s Theory of Acid – Base

 Less Soluble / Insoluble in polar H 2O

/ Aqueous Solvent
 This does not fulfill one of the basic
Criterias of the titration
 The analyte must be soluble in a
solvent to form the analytical
solution
 The Strong Acidic or Basic titrant
will rapidly react with
compound / Analyte
Arrhenius’s Acid – Base Theory
 According to Arrhenius’s Acid – Base Theory
–
 An Acid is a substance that can donate
Protons or Hydrogen ions (H+) in
water.
 E.g. – HCl in Water
the

Different Acid – Base Theory

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 A Base is substance that can donate acids and bases where water is not
Hydroxyl ions (OH–) in water. produced.
 E.g. – NaOH in Water  E.g. – Neutralization of HCl by
Mercuric Acetate produces
mercuric chloride and Acetic Acid
but not Water.
 Neutralization is an interaction
between an Acid and a Base to
produce Salt and Water.
 E.g. – Hydrochloric Acid (HCl) is Bronsted – Lowry Theory of Acid
neutralized by Sodium Hydroxide – Base
(NaOH) to produce Sodium
 According to Bronsted – Lowry Theory of
chloride (NaCl) salt and water
Acid and Base –
(H2O).
 An Acid is a substance that dissociates
into a proton (H+) and its conjugate
base.
 A Base is a substance that accepts the
Limitations of Arrhenius’s Acid –
Base Theory proton (H+) and forms its conjugate
acid.
1. Arrhenius’s Acid – Base Theory does not
 The general reactions can be represented as
explain the acidity or basicity of
–
compounds in non – aqueous medium.
E.g. Acidity of Acetic Acid is Liquid
Ammonia.
2. This theory cannot explain the acidity or
basicity of ions.
3. Acidity or Basicity shown by compounds
which do not donate H+ or OH-
respectively cannot be explained by this
theory. Advantages of Bronsted – Lowry
Theory of Acid – Base
4. This theory cannot explain the
neutralization reaction between those

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 1. This theory can explain the theory of aqueous medium. E.g. Neutralization of
both neutral species and also ions. Here HCl by Mercuric acetate in Acetic Acid.
–
 An acid can be –
 Neutral Species (E.g. – HCl)
 Cationic Species (E.g. – H3O+)
 Anionic Species (E.g. – H2PO4-)

Table 1: Diff erent Acids in Bronsted – Lowry

Theory

Proto Conjugate
Acid  +
n Bases
Figure 2: Neutralizati on of HCl by Mercuric acetate
HCl  H+ + Cl- in Aceti c Acid

H3O+  H+ + H2O Limitations of Bronsted – Lowry

Theory of Acid – Base
H2PO4-  H+ + HPO42-
1. According to Bronsted – Lowry theory –

 A Base can be –  An acid shows its acidity in the

 Neutral (E.g. – C5H5N) presence of a base

 Anionic Species (HPO42-)  A Base shows its basicity in the

presence of an acid
Table 2: Diff erent Bases in Bronsted – Lowry
2. It does not explain the acidity shown by
Theory
Non – Protic compounds. E.g. – BF3,
Conjugate
Base + Proton 
Acid BCl3, Ag+ etc.

C5H5N + H+  C5H5NH+
Lewis’ Theory of Acid – Base
HPO 4
2-
+ H+
 H2PO 4
-

 In Lewis’ Theory of Acid – Base –

2. This theory can explain the acidity and  An Acid is a Compound / Atom / Ion
basicity shown by same compounds. capable of accepting one / one pair /
E.g. – pairs of electron from a base; Thus
 Water referring as Lewis Acid.
 Acetic Acid  E.g. – H+ is a Lewis acid, since it can
3. This theory is capable of explaining the accept an electron to fulfill its outer
neutralization reaction in non – shell.

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 H+ + e-  H
 A Base is a Compound / Atom / Ion
capable of donating one / one pair /
pairs of electron to an acid; Thus
referring as Lewis Base.
-
 E.g. – AlCl is a Lewis Base, since it
4
can donate a pair of electrons
AlCl4-  AlCl3 + 2e-
 So, according to this theory, a neutralization
reaction is a formation of Coordinate
Covalent Bond between the donors and
acceptors of electron pair atoms. E.g. –
Reaction between Boron trichloride and
Triethylamine.
Figure 3: Reacti on between Boron trichloride and
Triethylamine
Advantages of Lewis’ Concept of
Acid – Base
 Lewis’ Concept of Acid and Base can
explain the acidity / basicity of any
molecule / atom / ion in any type of
solvent.
Strength of Acid & Base
Strength of Acid
 Strength of Acid depends on –
1. Dissociation of an Acid into Proton (H+)
2. Environment / Solvent in which the acid
dissociates
 This can be explained for both Strong and
Weak Acid.
Explanation for a Strong Acid (S A )
 A Strong Acid (SA) such as HCl will
slowly dissociate into proton (H+) and
Chloride ion (Cl-) in Acetic Acid
(CH3COOH) than in H2O; and thus acts
as a Weak Acid in Acetic Acid.
 It is because, H2O is more basic than
that of Acetic Acid (CH3COOH) and thus
can rapidly accept H+ than that of Acetic
Acid (CH3COOH).
 This is because, the higher the pkb value
of a compound the lower is the basicity
–
 pkb of H2O = 7
 pkb of CH3COOH = 9.25
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Table 3: Strength of Hydrochloric Acid in diff erent Solvents

HCl in H2O Acts as a Strong Acid

HCl  H+ + Cl- [Rapid Dissociation]

Hydrochloric Acid Proton Chloride ion

H2O + H+  H3O+ [Rapid Acceptance]

Water Proton Hydronium Ion

HCl in CH3COOH acts a Weak Acid

HCl  H+ + Cl- [Slow Dissociation]

Hydrochloric Acid Proton Chloride ion

CH3COOH + H+  CH3COOH2+ [Slow Acceptance]

Acetic Acid Proton Onium ion

Explanation for a Weak Acid (W A ) H2O and thus can rapidly accept H+
released by Acetic Acid.
 A Weak Acid (WA) such as Acetic Acid
 This is because; the higher the pkb value
(CH3COOH) will rapidly dissociate into
of a compound the lower is the basicity
Proton (H+) and Acetate ion (CH3COO-)
–
in Liquid Ammonia than in H2O; thus
 pkb of Ammonia = 4.75
act as a Strong Acid in NH3.
 pkb of H2O = 7
 It is because, Ammonia (NH3) is a
stronger base (pkb = 4.75) than that of

Table 4: Strength of Aceti c Acid in diff erent Solvents

Acetic Acid in H2O acts as Weak Acid

CH3COOH  H+ + CH3COO- [Slow Dissociation]

Acetic Acid Proton Acetate Ion

H2O + H+  H3O+ [Slow Acceptance]

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 Water Proton Hydronium Ion
Acetic Acid in Liquid Ammonia acts as Strong Acid

CH3COOH  H+ + CH3COO- [Rapid Dissociation]

Acetic Acid Proton Acetate ion

NH3 + H+  NH4+ [Rapid Acceptance]

Liquid Ammonia Proton Ammonium ion

Solvents used in Non – Aqueous Acid – Base  Used to provide rapid dissolution of
Titration
weak acids analytes where it can rapidly
 Solvents used in Non – Aqueous Acid – Base donate proton (H+) and behave like a
Titration are – strong acid
1. Protophillic Solvent  Protophillic Solvents accept H+ released by
2. Protogenic Solvent the weak acid and form –
3. Amphiprotic Solvent  Solvated Proton
4. Aprotic Solvents  Conjugate Acid of the Basic Solvent
 React with the employed strong
Protophillic Solvent
base titrant
 Protophillic Solvents are –  Conjugate Base of Weak Acid by
 Proton – loving Compounds for having reacting with Weak Acid Analyte
high affinity to accept proton (H+)  Effect produced by these solvents is called
 Basic in Nature; Also called Basic Leveling Effect.
Solvents  E.g. – Acetone, Ether such Dioxane, Liquid
Ammonia

Table 5: Leveling Eff ect of Protophillic Solvent on Weak Acid Analyte

HWA  H+ + WA-
Weak Acid Analyte Proton Conjugate Base of WA

S + H+  SH+

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 Protophillic
Proton Solvated Proton
Solvent

SB + SH+  S B H+ + S
Strong Base Solvated Conjugated Acid of
Protophillic Solvent
Titrant Proton Strong Base

HWA + SB  WA- + S B H+
Weak Acid Strong Base Conjugated Acid of
Conjugate Base of WA
Analyte Titrant Strong Base

Protogenic Solvent that rapidly accepts the H+ released by the

Strong Acid titrant
 Protogenic Solvents are –
 Effect produced by these solvents is called
 Proton – generating Solvents for rapid
Leveling Effect.
release of proton (H+)
 E.g. –
 Acidic in Nature; also called Acidic
 Formic Acid
Solvents
 Glacial Acetic Acid
 Used to provide rapid dissolution of
 Sulfuric Acid
weak acid analyte where it can rapidly
 Liquid HCl
+
accept H and behave like a strong base.
 Liquid HF
 Protogenic Solvents generate / donate H +

and forms Conjugate Base of Acidic Solvent

Table 6: Leveling Eff ect of Protophillic Solvent on Weak Base Analyte

HS  H+ + S-
Conjugate Base of
Acidic Solvent Proton
Acidic Solvent

B + H+  BH+
Weak Base Analyte Proton Conjugate Acid of Weak Base Analyte

HSA  H+ + SA -
Strong Acid Titrant Proton Conjugate Base Strong

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 Acid Titrant

S- + H+  HS
Conjugate Base of
Proton Acidic Solvent
Acidic Solvent
B + HSA  BH+ + SA -
Strong Acid Conjugate Acid of Weak Conjugate Base Strong
Weak Base Analyte
Titrant Base Analyte Acid Titrant

Amphiprotic Solvents  Solvents of this category produce Leveling

Effect on both Weak Acid and Base Analyte
 Amphiprotic Solvents are capable of acting
 E.g. – Glacial Acetic Acid, Alcohols
as both H+ acceptor and donor.

Table 7: Aceti c Acid Acti ng as a Protogenic Solvent

Acetic Acid Acting as a Protogenic Solvent

CH3COOH  H+ + CH3COO-
Acetic Acid Proton Acetate Ion (Conj. Base)

B + H+  BH+
Weak Base Analyte Conjugate Acid of Weak Base Analyte
Table 8: Aceti c Acid Acti ng as a Protophillic Solvent

Acetic Acid Acting as a Protophillic Solvent

HA  H+ + A-
Weak Acid Analyte Proton Conjugate Base of Weak Acid

CH3COOH + H+  CH3COOH2+
Acetic Acid Proton Onium ion (Conj. Acid)

Aprotic Solvents  They are also called Neutral Solvents

 E.g. –
 Aprotic Solvents are chemically inert for
 Hydrocarbons
neither accepting nor donating protons

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  Carbon Tetrachloride (CCl4) Saccharine 1.6 Apomorphine 7.00
 Chloroform
 Benzene  And, compounds which have pk a values
close to –
Reasons for using Aprotic Solvents  14 (or 4 – 14) are Weak Acids

1. Aprotic Solvents are used to increase  14 (or 9 – 14) are Strong Base

the volume of the analytical solution for

Table 10: pk a values of some Weak Acid and Strong
easy and accurate detection of End – Bases

point Weak Acid Strong Base

pka pka
2. They are used as additives in various
Caffeine 14.00 Ammonia 9.25
titration methods
Phenol 9.99 Amphetamine 9.37
3. They are useful to study the reaction
Sulfanilamid
10.43 Ephedrine 9.6
free of solvents effects. e
Acetic Acid 4.75 Trimethylamine 9.74
Theory of Non – aqueous Acid – Base Titration
 So, Non – aqueous acid – base titration is
 Acidity of Compounds falls from strong to
performed for those compounds which are
weak with increasing value from 1 to 14 on
–
the pka scale.
 Partially soluble or insoluble in H2O
 And, Basicity of compounds falls from  Acidic compounds with pka 4 – 14
strong to weak with decreasing value from
 Basic Compounds with pka 1 – 4
14 to 1 on the pka scale.
 So, compounds which have pk a value close Titration of Weak Acid (W A )
to –
Theory
 1 (or 1 – 3) is a Strong Acid
 1 (or 1 – 9) is Weak Base  Here, a WA analyte is titrated by a
Strong Base (SB) titrant in a Non –
Table 9: pk a values of some Strong Acid and Weak Aqueous Protophillic / Basic Solvent.
Bases
 In this case, the WA analyte reacts with
Strong Acid pka Weak Base pka
the Protophillic / Basic solvent and
Benzylpenicillin 2.76 Benzocaine 2.78
forms the Solvated Proton Species (A
Aspirin 3.49 Aniline 4.58
Conjugated Acid of the Protophillic
Picric Acid 0.38 Sulfadiazine 2.00

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 Solvent) which ultimately reacts with  So, the general reaction can be written
the SB Titrant. as –

Table 11: Titrati on of Weak Acid by Strong Base Titrant in a Basic Solvent

HWA  H+ + WA-
Weak Acid Analyte Proton Conjugate Base of WA

S + H+  SH+
Protophillic
Proton Solvated Proton
Solvent

SB + SH+  S B H+ + S
Strong Base Solvated Conjugated Acid of
Protophillic Solvent
Titrant Proton Strong Base

HWA + SB  WA- + S B H+
Weak Acid Strong Base Conjugated Acid of
Conjugate Base of WA
Analyte Titrant Strong Base

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 layer of N2 (or other inert gases) is
laid over the titrant.
 The entire device is sealed with
Teflon stopcocks.

Analytical / Titration Vessel for Analysis

Figure 5: Titrati on Vessel

 The analyte reacts with the basic

solvent to form the solvated
proton, a very reactive species and
can also react with the atmospheric
Figure 4: Titrati on Vessel and Burett e for Non – compounds
aqueous Titrati on of Weak Acid
 So, A Three – necked Flask is used
Apparatus for Controlled to –
Environment
 Protect the Analytical Solution
Burette for protecting the Titrant from the atmosphere
 Obtain Accurate Result
 Titrants used in Non – Aqueous
 Perform the titration in
Titration of Weak Acid are very
Controlled Environment
reactive and can react with
 The Middle neck of the flask
atmospheric compounds like
provides the entry of burette tip.
Oxygen.
 The Left and Right necks provide
 So for obtaining accurate result, the
the entry and exit of the N2 gas (or
titrant is protected from the
other inert gas) respectively.
atmosphere by a special burette
with reservoir which is flushed out
Practical Example
with N2 (or other inert gases) and a

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  A Practical Example of Non – aqueous
Titration of Weak Acid is the titration of
Benzoic Acid in n – butylamine by
Sodium methoxide
 Here,
 Benzoic Acid (Weak Acid Analyte,
pka = 4.2)
 Sodium methoxide (CH3ONa, Strong
Base Titrant)
 n – butylamine (Basic / Protophillic
Solvent)
 So, the reaction can be –

Figure 6: Titrati on of Weak Acid by Strong Base

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 Titration of Weak Base (W B )
Theory
 In the titration of Weak Base (WB) or a
H2O – insoluble / Poorly H2O – soluble
Strong Base (SB), the analyte is titrated
by a Strong Acid (SA) titrant in
Protogenic / Acidic Solvent.
 SA Titrant is dissolved in the Protogenic
Solvent to make the Solvated Proton
Species and Conj. Base of SA Titrant.
Here, the Protogenic Solvent acts as a
base in the stronger acidic SA Titrant.
 When, the Analyte is dissolved in the
Protogenic Solvent, they will react with
each other to form –
1. Conjugate (Conj.) Acid of WB
2. Conj. Base of SA
 Then, the Solvated Proton Species and
Conjugate (Conj.) Base of Acidic
Solvent to form the Acidic Solvent

HSA + HA  H2A+ + SA -
Solvated Proton
SA Titrant Acidic Solvent Conj. Base of SA
Species
WB + HA  HWB+ + A-
Conj. Base of Acidic
WB Analyte Acidic Solvent Conj. Acid of WB
Solvent
H2A+ + A-  2HA
Solvated Proton Conj. Base of Acidic
Acidic Solvent
Species Solvent
WB + HSA  HWB+ + SA -
WB Analyte SA Titrant Conj. Acid of WB Conj. Base of SA

 When, the analyte is dissolved in the  Acidic Solvent

Aprotic Solvent, Solvated Proton
Species and WB Analyte will react to
form –
 Conj. Acid of WB

HSA + HA  H2A+ + SA -
Solvated Proton
SA Titrant Acidic Solvent Conj. Base of SA
Species

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 WB + H2A +  HWB+ + HA
Solvated Proton
WB Analyte Conj. Acid of WB Acidic Solvent
Species
WB + HSA  HWB+ + SA -
WB Analyte SA Titrant Conj. Acid of WB Conj. Base of SA

Practical Example – 1  Ephedrine in Glacial Acetic Acid is

titrated by Perchloric Acid in Acetic
 Although Ephedrine is a Strong Base
Acid.
(pka = 9.6), it is titrated in non –
 The Reactions are illustrated as –
aqueous solvent for being poorly
soluble in H2O.

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Figure 7: Titrati on of Ephedrine in Aceti c Acid by Acetous Perchloric Acid

Practical Example – 2  Ephedrine in Aprotic Solvents such as

CCl4, Benzene, and CHCl3 etc. is titrated
by Perchloric Acid in Dioxane.
 The Reactions are illustrated as –

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Figure 8: Titrati on of Ephedrine in Aproti c Acid by Perchloric Acid in Dioxane

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