East West University

Non-aqueous Acid-Base Titration

PHRM-309

Tareq Hasan 10/6/2011

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 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

DIFFERENT ACID BASE THEORY...................................3 Arrheniuss Acid Base Theory .........................3

Limitations of Arrheniuss Acid Base Theory .....3

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

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

Titration of Weak Base (WB) ...........................14

Theory ................................................................ 14 Practical Example 1 ......................................... 15 Practical Example 2 ......................................... 16

STRENGTH OF ACID & BASE .........................................6 Strength of Acid ................................................6

Explanation for a Strong Acid (SA) ........................6

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Non Aqueous Acid Base Titration

In tro d u cti o n

1. Interaction of the Titrant with H2O 2. Poor Solubility of Weakly Acidic (WA) or Weakly Basic (WB) Analyte in H2O

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.

Interaction of H 2 O 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

Reasons for Performing Non Aqueous Acid Base Titration

Non aqueous Acid Base Titration is performed to eliminate 2 problems

properties. As a result More titrant will be required Detected end point will give wrong result or no end point will occur

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

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

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Poor Solubility of Weak Acids (W A ) or Weak Bases (W B ) in H 2 O

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

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

compound / Analyte
Diffe r en t Ac id B ase T h eo r y

chloride (NaCl) salt and water (H2O).

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

Limitations of Arrheniuss Acid Base Theory

1. Arrheniuss Acid Base Theory does not explain the acidity or basicity of compounds in non aqueous medium.

Arrheniuss Acid Base Theory

According to Arrheniuss Acid Base Theory An Acid is a substance that can donate Protons or Hydrogen ions (H ) in water. E.g. HCl in Water
+

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-

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respectively cannot be explained by this theory. 4. This theory cannot explain the

Advantages of Bronsted Lowry Theory of Acid Base

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

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.

Acid HCl

Proton + H+ H+ H+ + + +

Conjugate Bases ClH2O HPO42-

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
+

H3O+ H2PO4-

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

Table 2: Different Bases in Bronsted Lowry Theory

Base C5H5N

+ +

Proton H+ H+

Conjugate Acid C5H5NH+ H2PO4-

HPO42- +

2. This theory can explain the acidity and basicity shown by same compounds. E.g. Water 4|Page

 Acetic Acid 3. This theory is capable of explaining the neutralization reaction in non

E.g. H+ is a Lewis acid, since it can accept an electron to fulfill its outer shell.

aqueous medium. E.g. Neutralization of HCl by Mercuric acetate in Acetic Acid.

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 + 2eFigure 2: Neutralization of HCl by Mercuric acetate in Acetic Acid

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.

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 Ac id 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.
Figure 3: Reaction between Boron trichloride and Triethylamine

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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 ren g t h o f Ac id & Ba se

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

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.
Table 3: Strength of Hydrochloric Acid in different Solvents

HCl in H2O Acts as a Strong Acid

HCl
Hydrochloric Acid

H+
Proton

ClChloride ion

[Rapid Dissociation]

H2O
Water

H+
Proton

H3O+
Hydronium Ion

[Rapid Acceptance]

HCl in CH3COOH acts a Weak Acid

HCl
Hydrochloric Acid

H+
Proton

ClChloride ion

[Slow Dissociation]

CH3COOH
Acetic Acid

H+
Proton

CH3COOH2+
Onium ion

[Slow Acceptance]

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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
Table 4: Strength of Acetic Acid in different Solvents

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

Acetic Acid in H2O acts as Weak Acid CH3COOH Acetic Acid H2O Water + H+ Proton H+ Proton + CH3COOAcetate Ion H3O+ Hydronium Ion [Slow Acceptance] [Slow 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] [Rapid Dissociation]

Sol vent s u s ed in N o n A q u eo u s Ac id Bas e T i tr atio n

Protophillic Solvent
Protophillic Solvents are Proton loving Compounds for having high affinity to accept proton (H+) Basic in Nature; Also called Basic Solvents

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

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 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
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 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. 8|Page

 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.
Table 7: Acetic Acid Acting as a Protogenic Solvent

Solvents of this category produce Leveling Effect on both Weak Acid and Base Analyte E.g. Glacial Acetic Acid, Alcohols

Acetic Acid Acting as a Protogenic Solvent

CH3COOH
Acetic Acid

+ H+

H+
Proton

CH3COOAcetate Ion (Conj. Base)

B
Weak Base Analyte

BH+
Conjugate Acid of Weak Base Analyte

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Table 8: Acetic Acid Acting as a Protophillic Solvent

Acetic Acid Acting as a Protophillic Solvent

HA
Weak Acid Analyte

H+
Proton

H+
Proton

AConjugate Base of Weak Acid

CH3COOH +
Acetic Acid

CH3COOH2+
Onium ion (Conj. Acid) Acidity of Compounds falls from strong to weak with increasing value from 1 to 14 on

Aprotic Solvents
Aprotic Solvents are chemically inert for neither accepting nor donating protons They are also called Neutral Solvents E.g. Hydrocarbons Carbon Tetrachloride (CCl4) Chloroform Benzene

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

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. And, compounds which have pka values
Theo ry o f No n aq u eo u s Ac id B ase T itr atio n
Table 9: pk a values of some Strong Acid and Weak Bases

Strong Acid

pka

Weak Base Benzocaine Aniline Sulfadiazine

pka 2.78 4.58 2.00

Benzylpenicillin 2.76 Aspirin Picric Acid Saccharine 3.49 0.38 1.6

Apomorphine 7.00

close to 14 (or 4 14) are Weak Acids 14 (or 9 14) are Strong Base

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Table 10: pk a values of some Weak Acid and Strong Bases

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

Weak Acid Caffeine Phenol

pka 14.00 9.99

Strong Base Ammonia Amphetamine Ephedrine

pka 9.25 9.37 9.6

Sulfanilamide 10.43 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

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

compounds So, A Three necked Flask is used to Protect the Analytical Solution from the atmosphere Obtain Accurate Result Perform the titration in

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 like

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.

atmospheric Oxygen.

compounds

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

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
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

Acidic Solvent

Species and WB Analyte will react to form Conj. Acid of WB

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

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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

Figure 7: Titration of Ephedrine in Acetic Acid by Acetous Perchloric Acid

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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

Figure 8: Titration of Ephedrine in Aprotic Acid by Perchloric Acid in Dioxane

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