East West University

Non-aqueous Acid-Base Titration

PHRM-309

Tareq Hasan10/6/2011

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

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

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N o n – A q u e o u s A c i d – B a s e T i t r a t i o n

In t roduct ion

A Non – Aqueous Acid – Base Titration

involves the titration by neutralization of

either acid or base by their opposite entities

in a non – aqueous medium.

Reasons for Performing Non – Aqueous Acid – Base Titration

Non – aqueous Acid – Base Titration is

performed to eliminate 2 problems

encountered during the aqueous titration of

weakly acidic or weakly basic analyte by a

Strong Acid or Strong Base Titrant

respectively.

The 2 problems are –

1. Interaction of the Titrant with H2O

2. Poor Solubility of Weakly Acidic (WA) or

Weakly Basic (WB) Analyte in H2O

Interaction of H2O with the Titrant

In the aqueous titration of a Weakly

Acidic / Weakly Basic Analyte by a

Strongly Basic / Strongly Acidic Titrant

respectively, the solvent also reacts

with the titrant, because of having both

Weakly Acidic and Weakly Basic

properties.

As a result –

More titrant will be required

Detected end – point will give

wrong result or no end – point will

occur

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Figure 1: Reaction of Water with titrants in Aqueous Titration of Weak Acid or Weak Acid

Poor Solubility of Weak Acids (W A) or Weak Bases (WB) in H2O

Most of the WA or WB Analytes are –

Non – Polar

Organic

Less Soluble / Insoluble in polar H2O

/ 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 the

compound / Analyte

Dif ferent Acid – Base Theory

Broadly, acid – base theories are classified

into –

1. Arrhenius’s Acid – Base Theory

2. Bronsted – Lowry Theory of Acid – Base

3. Lewis’s Theory of Acid – Base

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

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A Base is substance that can donate

Hydroxyl ions (OH–) in water.

E.g. – NaOH in Water

Neutralization is an interaction

between an Acid and a Base to

produce Salt and Water.

E.g. – Hydrochloric Acid (HCl) is

neutralized by Sodium Hydroxide

(NaOH) to produce Sodium

chloride (NaCl) salt and water

(H2O).

Limitations of Arrhenius’s Acid – Base Theory

1. Arrhenius’s Acid – Base Theory does not

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.

4. This theory cannot explain the

neutralization reaction between those

acids and bases where water is not

produced.

E.g. – Neutralization of HCl by

Mercuric Acetate produces

mercuric chloride and Acetic Acid

but not Water.

Bronsted – Lowry Theory of Acid – Base

According to Bronsted – Lowry Theory of

Acid and Base –

An Acid is a substance that dissociates

into a proton (H+) and its conjugate

base.

A Base is a substance that accepts the

proton (H+) and forms its conjugate

acid.

The general reactions can be represented as

–

Advantages of Bronsted – Lowry Theory of Acid – Base

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1. This theory can explain the theory of

both neutral species and also ions. Here

–

An acid can be –

Neutral Species (E.g. – HCl)

Cationic Species (E.g. – H3O+)

Anionic Species (E.g. – H2PO4-)

Table 1: Different Acids in Bronsted – Lowry Theory

Acid Proton + Conjugate Bases

HCl H+ + Cl-

H3O+ H+ + H2O

H2PO4- H+ + HPO4

2-

A Base can be –

Neutral (E.g. – C5H5N)

Anionic Species (HPO42-)

Table 2: Different Bases in Bronsted – Lowry Theory

Base + Proton Conjugate Acid

C5H5N + H+ C5H5NH+

HPO42- + H+ H2PO4

-

2. This theory can explain the acidity and

basicity shown by same compounds.

E.g. –

Water

Acetic Acid

3. This theory is capable of explaining the

neutralization reaction in non –

aqueous medium. E.g. Neutralization of

HCl by Mercuric acetate in Acetic Acid.

Figure 2: Neutralization of HCl by Mercuric acetate in Acetic Acid

Limitations of Bronsted – Lowry Theory of Acid – Base

1. According to Bronsted – Lowry theory –

An acid shows its acidity in the

presence of a base

A Base shows its basicity in the

presence of an acid

2. It does not explain the acidity shown by

Non – Protic compounds. E.g. – BF3,

BCl3, Ag+ etc.

Lewis’ Theory of Acid – Base

In Lewis’ Theory of Acid – Base –

An Acid is a Compound / Atom / Ion

capable of accepting one / one pair /

pairs of electron from a base; Thus

referring as Lewis Acid.

E.g. – H+ is a Lewis acid, since it can

accept an electron to fulfill its outer

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. – AlCl4- is a Lewis Base, since it

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: Reaction 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 different 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)

A Weak Acid (WA) such as Acetic Acid

(CH3COOH) will rapidly dissociate into

Proton (H+) and Acetate ion (CH3COO-)

in Liquid Ammonia than in H2O; thus

act as a Strong Acid in NH3.

It is because, Ammonia (NH3) is a

stronger base (pkb = 4.75) than that of

H2O and thus can rapidly accept H+

released by Acetic Acid.

This is because; the higher the pkb value

of a compound the lower is the basicity

–

pkb of Ammonia = 4.75

pkb of H2O = 7

Table 4: Strength of Acetic Acid in different 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 T i t ra t ion

Solvents used in Non – Aqueous Acid – Base

Titration are –

1. Protophillic Solvent

2. Protogenic Solvent

3. Amphiprotic Solvent

4. Aprotic Solvents

Protophillic Solvent

Protophillic Solvents are –

Proton – loving Compounds for having

high affinity to accept proton (H+)

Basic in Nature; Also called Basic

Solvents

Used to provide rapid dissolution of

weak acids analytes where it can rapidly

donate proton (H+) and behave like a

strong acid

Protophillic Solvents accept H+ released by

the weak acid and form –

Solvated Proton

Conjugate Acid of the Basic Solvent

React with the employed strong

base titrant

Conjugate Base of Weak Acid by

reacting with Weak Acid Analyte

Effect produced by these solvents is called

Leveling Effect.

E.g. – Acetone, Ether such Dioxane, Liquid

Ammonia

Table 5: Leveling Effect 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 Solvent

Proton Solvated Proton

SB + SH+ SBH+ + S

Strong Base Titrant

Solvated Proton

Conjugated Acid of Strong Base

Protophillic Solvent

HWA + SB WA- + SBH+

Weak Acid Analyte

Strong Base Titrant

Conjugate Base of WAConjugated Acid of

Strong Base

Protogenic Solvent

Protogenic Solvents are –

Proton – generating Solvents for rapid

release of proton (H+)

Acidic in Nature; also called Acidic

Solvents

Used to provide rapid dissolution of

weak acid analyte where it can rapidly

accept H+ and behave like a strong base.

Protogenic Solvents generate / donate H+

and forms Conjugate Base of Acidic Solvent

that rapidly accepts the H+ released by the

Strong Acid titrant

Effect produced by these solvents is called

Leveling Effect.

E.g. –

Formic Acid

Glacial Acetic Acid

Sulfuric Acid

Liquid HCl

Liquid HF

Table 6: Leveling Effect of Protophillic Solvent on Weak Base Analyte

HS H+ + S-

Acidic Solvent Proton Conjugate Base of 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 Acidic Solvent

Proton Acidic Solvent

B + HSA BH+ + SA-

Weak Base Analyte Strong Acid Titrant

Conjugate Acid of Weak Base Analyte

Conjugate Base Strong Acid Titrant

Amphiprotic Solvents

Amphiprotic Solvents are capable of acting

as both H+ acceptor and donor.

Solvents of this category produce Leveling

Effect on both Weak Acid and Base Analyte

E.g. – Glacial Acetic Acid, Alcohols

Table 7: Acetic Acid Acting 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: Acetic Acid Acting 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

Aprotic Solvents are chemically inert for

neither accepting nor donating protons

They are also called Neutral Solvents

E.g. –

Hydrocarbons

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Carbon Tetrachloride (CCl4)

Chloroform

Benzene

Reasons for using Aprotic Solvents

1. Aprotic Solvents are used to increase

the volume of the analytical solution for

easy and accurate detection of End –

point

2. They are used as additives in various

titration methods

3. They are useful to study the reaction

free of solvents effects.

Theory of Non – aqueous Acid – Base T i t ra t ion

Acidity of Compounds falls from strong to

weak with increasing value from 1 to 14 on

the pka scale.

And, Basicity of compounds falls from

strong to weak with decreasing value from

14 to 1 on the pka scale.

So, compounds which have pka value close

to –

1 (or 1 – 3) is a Strong Acid

1 (or 1 – 9) is Weak Base

Table 9: pka values of some Strong Acid and Weak Bases

Strong Acid pka Weak Base pka

Benzylpenicillin 2.76 Benzocaine 2.78

Aspirin 3.49 Aniline 4.58

Picric Acid 0.38 Sulfadiazine 2.00

Saccharine 1.6 Apomorphine 7.00

And, compounds which have pka values

close to –

14 (or 4 – 14) are Weak Acids

14 (or 9 – 14) are Strong Base

Table 10: pka values of some Weak Acid and Strong Bases

Weak Acid pka Strong Base pka

Caffeine 14.00 Ammonia 9.25

Phenol 9.99 Amphetamine 9.37

Sulfanilamide

10.43 Ephedrine 9.6

Acetic Acid 4.75 Trimethylamine 9.74

So, Non – aqueous acid – base titration is

performed for those compounds which are

–

Partially soluble or insoluble in H2O

Acidic compounds with pka 4 – 14

Basic Compounds with pka 1 – 4

Titration of Weak Acid (W A)

Theory

Here, a WA analyte is titrated by a

Strong Base (SB) titrant in a Non –

Aqueous Protophillic / Basic Solvent.

In this case, the WA analyte reacts with

the Protophillic / Basic solvent and

forms the Solvated Proton Species (A

Conjugated Acid of the Protophillic

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Solvent) which ultimately reacts with

the SB Titrant.

So, the general reaction can be written

as –

Table 11: Titration 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 Solvent

Proton Solvated Proton

SB + SH+ SBH+ + S

Strong Base Titrant

Solvated Proton

Conjugated Acid of Strong Base

Protophillic Solvent

HWA + SB WA- + SBH+

Weak Acid Analyte

Strong Base Titrant

Conjugate Base of WAConjugated Acid of

Strong Base

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Figure 4: Titration Vessel and Burette for Non – aqueous Titration of Weak Acid

Apparatus for Controlled Environment

Burette for protecting the Titrant

Titrants used in Non – Aqueous

Titration of Weak Acid are very

reactive and can react with

atmospheric compounds like

Oxygen.

So for obtaining accurate result, the

titrant is protected from the

atmosphere by a special burette

with reservoir which is flushed out

with N2 (or other inert gases) and a

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: Titration Vessel

The analyte reacts with the basic

solvent to form the solvated

proton, a very reactive species and

can also react with the atmospheric

compounds

So, A Three – necked Flask is used

to –

Protect the Analytical Solution

from the atmosphere

Obtain Accurate Result

Perform the titration in

Controlled Environment

The Middle neck of the flask

provides the entry of burette tip.

The Left and Right necks provide

the entry and exit of the N2 gas (or

other inert gas) respectively.

Practical Example

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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: Titration 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-

SA Titrant Acidic Solvent Solvated Proton Species

Conj. Base of SA

WB + HA HWB+ + A-

WB Analyte Acidic Solvent Conj. Acid of WBConj. Base of Acidic

SolventH2A+ + A- 2HA

Solvated Proton Species

Conj. Base of Acidic Solvent

Acidic Solvent

WB + HSA HWB+ + SA

-

WB Analyte SA Titrant Conj. Acid of WB Conj. Base of SA

When, the analyte is dissolved in the

Aprotic Solvent, Solvated Proton

Species and WB Analyte will react to

form –

Conj. Acid of WB

Acidic Solvent

HSA + HA H2A+ + SA-

SA Titrant Acidic Solvent Solvated Proton Species Conj. Base of SA

WB + H2A+ HWB+ + HA

WB Analyte Solvated Proton Species Conj. Acid of WB Acidic Solvent

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WB + HSA HWB+ + SA

-

WB Analyte SA Titrant Conj. Acid of WB Conj. Base of SA

Practical Example – 1

Although Ephedrine is a Strong Base

(pka = 9.6), it is titrated in non –

aqueous solvent for being poorly

soluble in H2O.

Ephedrine in Glacial Acetic Acid is

titrated by Perchloric Acid in Acetic

Acid.

The Reactions are illustrated as –

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Figure 7: Titration of Ephedrine in Acetic 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: Titration of Ephedrine in Aprotic Acid by Perchloric Acid in Dioxane

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