East West University

Non-aqueous Titration
PHRM-309

Acid-Base

Tareq Hasan 10/6/2011

Table of Contents
NON AQUEOUS ACID BASE TITRATION.............................................................3 INTRODUCTION............................................................................................................................3 Reasons for Performing Non Aqueous Acid Base Titration...........................................3
Interaction of H2O with the Titrant.............................................................................................. 3 Poor Solubility of Weak Acids (WA) or Weak Bases (WB) in H2O..................................................4

DIFFERENT ACID BASE THEORY......................................................................................................5 Arrheniuss Acid Base Theory........................................................................................5

Limitations of Arrheniuss Acid Base Theory............................................................................. 5

Bronsted Lowry Theory of Acid Base...........................................................................6

Advantages of Bronsted Lowry Theory of Acid Base............................................................... 6 Limitations of Bronsted Lowry Theory of Acid Base................................................................ 7

Lewis Theory of Acid Base............................................................................................7

Advantages of Lewis Concept of Acid Base.............................................................................. 8

STRENGTH

OF

ACID & BASE...........................................................................................................8

Strength of Acid...............................................................................................................8
Explanation for a Strong Acid (SA)............................................................................................... 8 Explanation for a Weak Acid (WA)............................................................................................... 9

SOLVENTS

USED IN

NON AQUEOUS ACID BASE TITRATION...................................................................10

Protophillic Solvent.........................................................................................................10 Protogenic Solvent.........................................................................................................11 Amphiprotic Solvents.....................................................................................................12 Aprotic Solvents.............................................................................................................13

Reasons for using Aprotic Solvents............................................................................................ 13

THEORY

OF

NON

AQUEOUS

ACID BASE TITRATION............................................................................13

Titration of Weak Acid (WA)...........................................................................................14

Theory....................................................................................................................................... 14 Apparatus for Controlled Environment...................................................................................... 16 Burette for protecting the Titrant........................................................................................... 16 Analytical / Titration Vessel for Analysis................................................................................ 16 Practical Example...................................................................................................................... 17

Titration of Weak Base (WB)..........................................................................................18

Theory....................................................................................................................................... 18 Practical Example 1................................................................................................................ 20 Practical Example 2................................................................................................................ 21

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Non Aqueous Acid Base Titration

Int ro d uct io n

or weakly basic analyte by a Strong Acid or Strong Base Titrant respectively. The 2 problems are 1. Interaction of the Titrant with H 2O 2. Poor Solubility of Weakly Acidic

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

(WA)

or

Weakly

Basic

(WB)

Analyte in H2O

Interaction of H 2 O with the Titrant

In the aqueous titration of a Weakly Acidic / Weakly Basic 3|Page

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

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 (W B ) in H2O

Most of the WA or WB Analytes are Non Polar

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

Organic Less Soluble / Insoluble in polar H2O / Aqueous Solvent

titrant will rapidly react with the compound / Analyte

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Diff e re nt Acid Bas e The o ry

and a Base to produce Salt and Water. E.g. Hydrochloric Acid (HCl) is neutralized by Sodium Hydroxide

Broadly,

acid base theories are

classified into 1. Arrheniuss Acid Base Theory 2. Bronsted Lowry Theory of Acid Base 3. Lewiss Theory of Acid Base

(NaOH) to produce Sodium chloride (NaCl) salt and water (H2O).

Arrheniuss Acid Base Theory

According to Arrheniuss Acid Base Theory An Acid is a substance that can donate Protons
+

Limitations of Arrheniuss Acid Base Theory

1. Arrheniuss 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

or

Hydrogen ions (H ) in water. E.g. HCl in Water

A Base is substance that can donate Hydroxyl ions (OH) in water. E.g. NaOH in Water

Neutralization

is

an

water is not produced.

interaction between an Acid

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 E.g.

Neutralization

of

1. This theory

can

explain

the

HCl by Mercuric Acetate produces but not Water. mercuric chloride and Acetic Acid

theory of both neutral species and also ions. Here An acid can be Neutral Species (E.g. HCl)

Bronsted Lowry Theory of Acid Base

According to Bronsted Lowry

Cationic Species (E.g. H3O+) Anionic Species (E.g. H2PO4-)

Table 1: Different Acids in Bronsted Lowry Theory

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

Acid HCl H3O+ H2P O4-

Prot on H+ H+ H+

+ + + +

Conjugate Bases ClH2O HPO42-

represented as

A Base can be Neutral (E.g. C5H5N) Anionic Species (HPO42-)

Table 2: Different Bases in Bronsted Lowry Theory

Advantages of Bronsted Lowry Theory of Acid Base

Bas e C5H5 N HPO

24

+ + +

Proto n H+ H+

Conjugate Acid C5H5NH+ H2PO4-

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2. This theory can

explain

the

2. It does not explain the acidity shown Ag+ etc. by Non Protic compounds. E.g. BF3, BCl3,

acidity and basicity shown by same compounds. E.g. Water Acetic Acid 3. This theory in is non capable of

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 shell. it can accept an electron to fulfill its outer

explaining reaction HCl by

the

neutralization aqueous in

medium. E.g. Neutralization of Mercuric acetate Acetic Acid.

H
+

+
is

e
-

H
a Compound /

Figure 2: Neutralization of HCl Mercuric acetate in Acetic Acid

by

Base

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

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

AlCl
4 -

AlCl
3

2 e-

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 So, according to this theory, a neutralization formation Covalent pair of Bond E.g. reaction is a the Coordinate between

Strength of Acid depends on 1. Dissociation Proton (H+) 2. Environment / Solvent in which the acid dissociates This can be explained for both Strong and Weak Acid. of an Acid into

donors and acceptors of electron atoms. Reaction and between Boron trichloride

Triethylamine.

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
Figure 3: Reaction between trichloride and Triethylamine Boron

that

of

Acetic thus

Acid can

(CH3COOH)

and

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.
St re ng t h of Acid & Bas e

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

Strength of Acid

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Table 3: Strength of Hydrochloric Acid in different Solvents

HCl in H2O Acts as a Strong Acid

HCl
Hydrochloric Acid

H+
Proto n

ClChloride ion

[Rapid Dissociation]

H2O
Water

H+
Proto n

H3O+
Hydronium Ion

[Rapid Acceptance]

HCl in CH3COOH acts a Weak Acid

HCl
Hydrochloric Acid

H+
Proto n

ClChloride ion

[Slow Dissociation]

CH3COO H
Acetic Acid

H+
Proto n

CH3COOH2+
Onium ion

[Slow Acceptance]

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.

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

It is because, Ammonia (NH3) is a stronger base (pkb = 4.75)

Table 4: Strength of Acetic Acid in different Solvents

Acetic Acid in H2O acts as Weak Acid

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CH3COOH Acetic Acid H2O Water + H+ Proton

H+ Proton

CH3COOAcetate Ion H3O+

[Slow Dissociation]

[Slow Acceptance]

Hydronium Ion [Rapid Dissociation]

Acetic Acid in Liquid Ammonia acts as Strong Acid CH3COOH Acetic Acid NH3 Liquid Ammonia + H+ Proton H+ Proton + CH3COOAcetate ion NH4+ Ammonium ion [Rapid Acceptance]

So lve nt s us e d in No n Aq ue o us Acid Bas e Tit rat io n

Basic

in Nature;

Also called

Basic Solvents Used to provide of weak rapid acids

Solvents used in Non Aqueous Acid Base Titration are 1. Protophillic Solvent 2. Protogenic Solvent 3. Amphiprotic Solvent 4. Aprotic Solvents dissolution

analytes where it can rapidly donate proton (H+) and behave like a strong acid Protophillic form Solvated Proton Conjugate Acid of the Basic Solvent React with the employed Solvents accept H+

released by the weak acid and

Protophillic Solvent
Protophillic Solvents are Proton loving Compounds for having high affinity to accept proton (H+)

strong base titrant 10 | P a g e

 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
Weak Acid Analyte

H+
Proton

WAConjugate Base of WA

S
Protophillic Solvent

H+
Proton

SH+
Solvated Proton

SB
Strong Base Titrant

SH+
Solvated Proton

SBH+
Conjugated Acid of Strong Base

S
Protophillic Solvent

HWA
Weak Acid Analyte

SB
Strong Base Titrant

WAConjugate Base of WA

SBH+
Conjugated Acid of Strong Base

Protogenic Solvent
Protogenic Solvents are Proton proton (H+) Acidic in Nature; also called Acidic Solvents Used to provide rapid generating

where it can rapidly accept H+ and behave like a strong base. Protogenic donate H Base
+

Solvents Acidic

generate

Solvents for rapid release of

and forms Conjugate Solvent that

of

rapidly accepts the H+ released by the Strong Acid titrant Effect produced by these solvents is called Leveling Effect.

dissolution of weak acid analyte 11 | P a g e

 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
Acidic Solvent

H+
Proton

SConjugate Base of Acidic Solvent

B
Weak Base Analyte

H+
Proton

BH+
Conjugate Acid of Weak Base Analyte

HSA
Strong Acid Titrant

H+
Proton

SAConjugate Base Strong Acid Titrant

SConjugate Base of Acidic Solvent

H+
Proton

HS
Acidic Solvent

B
Weak Base Analyte

HSA
Strong Acid Titrant

BH+
Conjugate Acid of Weak Base Analyte

SAConjugate 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 12 | P a g e

CH3COOH
Acetic Acid

H
+

H+
Proto n

CH3COOAcetate Ion (Conj. Base)

B
Weak Base Analyte

BH+
Conjugate Acid of Weak Base Analyte

Table 8: Acetic Acid Acting as a Protophillic Solvent

Acetic Acid Acting as a Protophillic Solvent

HA
Weak Acid Analyte

H+
Proto n

AConjugate Base of Weak Acid

CH3CO OH
Acetic Acid

+ H+
Proto n

CH3COOH2+
Onium ion (Conj. Acid)

Aprotic Solvents
Aprotic inert Solvents neither are chemically nor

1. Aprotic Solvents are used to increase the volume of the analytical solution for easy and accurate detection of End point

for

accepting

donating protons They are also called Neutral

Solvents E.g. Hydrocarbons Carbon Tetrachloride (CCl4) Chloroform Benzene

2. They are used as additives in various titration methods 3. They are useful to study the reaction free of solvents effects.
The o ry of No n aq ueo us Acid Bas e Tit rat io n

Acidity of Compounds falls from strong to weak with increasing value from 1 to 14 on the pka scale.

Reasons for using Aprotic Solvents

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 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: pk a values of some Strong Acid and Weak Bases

Sulfanilam ide Acetic Acid

10.4 3 4.75

Ephedrine Trimethylam ine

9.6 9.7 4

So, Non aqueous acid base titration is performed for those compounds which are Partially soluble or insoluble in H 2O Acidic compounds with pka 4 14 Basic Compounds with pka 1 4

Strong Acid Benzylpenic illin Aspirin Picric Acid Saccharine

pka 2.76 3.49 0.38 1.6

Weak Base Benzocain e Aniline Sulfadiazin e Apomorphi ne

pka 2.78 4.58 2.00 7.00

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

And, compounds which have pka values close to 14 (or 4 14) are Weak Acids 14 (or 9 14) are Strong Base
Table 10: pk a values of some Weak Acid and Strong Bases

reacts with the Protophillic / Basic solvent and forms the Solvated Proton Species (A Conjugated Protophillic Titrant. So, the general reaction can be written as Acid of the which Solvent)

Weak Acid Caffeine Phenol

pka 14.0 0 9.99

Strong Base Ammonia

pka

ultimately reacts with the SB

9.2 5 Amphetamin 9.3 e 7

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

HWA
Weak Acid Analyte

H+
Proton

WAConjugate Base of WA

S
Protophillic Solvent

H+
Proton

SH+
Solvated Proton

SB
Strong Base Titrant

SH+
Solvated Proton

SBH+
Conjugated Acid of Strong Base

S
Protophillic Solvent

HWA
Weak Acid Analyte

SB
Strong Base Titrant

WAConjugate Base of WA

SBH+
Conjugated Acid of Strong Base

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is flushed out with N2 (or other inert gases) and a layer of N2 (or other inert gases) titrant. The entire device is sealed with Teflon stopcocks. Analytical / Titration Vessel for Analysis is laid over the

Figure 5: Titration Vessel Figure 4: Titration Vessel and Burette for Non aqueous Titration of Weak Acid

The analyte reacts with the basic solvent to form the solvated reactive also proton, species react a and very can the

Apparatus for Controlled Environment

Burette for protecting the Titrant Titrants used in Non

with

atmospheric compounds So, A Three necked Flask is used to Protect Solution atmosphere Obtain Accurate Result Perform the titration in Controlled Environment 16 | P a g e the Analytical the

Aqueous Titration of Weak Acid are very reactive and can react with atmospheric compounds like Oxygen. So for obtaining the by from a accurate is the special

from

result, protected

titrant

atmosphere

burette with reservoir which

 The Middle neck of the flask provides the entry of burette tip.

butylamine

by

Sodium

methoxide Here,

The Left and Right necks provide the entry and exit of the N2 gas (or other inert gas) respectively. Benzoic Acid (Weak Acid Analyte, pka = 4.2) Sodium (CH3ONa, Titrant) n butylamine (Basic / methoxide Strong Base

Practical Example
A Practical Example of Non aqueous Titration of Weak Acid is the titration of Benzoic Acid in

Protophillic Solvent) So, the reaction can be

17 | P a g e

Figure 6: Titration of Weak Acid by Strong Base

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 18 | P a g e

acts as a base in the stronger acidic SA Titrant.

2. Conj. Base of SA Then, the Solvated and Base of Proton Acidic

When, the Analyte is dissolved in the Protogenic Solvent, they will react with each other to form 1. Conjugate (Conj.) Acid of WB

Species (Conj.) Solvent

Conjugate

Solvent to form the Acidic

HSA
SA Titrant

+ + + +

HA
Acidic Solvent

H2A+
Solvated Proton Species

+ +

SAConj. Base of SA

WB
WB Analyte

HA
Acidic Solvent

HWB+
Conj. Acid of WB

AConj. Base of Acidic Solvent

H2A+
Solvated Proton Species

AConj. Base of Acidic Solvent

2HA
Acidic Solvent

WB
WB Analyte

HSA
SA Titrant

HWB+
Conj. Acid of WB

SAConj. 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
SA Titrant

+ + +

HA
Acidic Solvent

H2A+
Solvated Proton Species

+ + +

SAConj. Base of SA

WB
WB Analyte

H2A+
Solvated Proton Species

HWB+
Conj. Acid of WB

HA
Acidic Solvent

WB
WB Analyte

HSA
SA Titrant

HWB+
Conj. Acid of WB

SAConj. Base of SA 19 | P a g e

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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