Non-aqueous acid base titrimetry

Non- aqueous titrations are those in which the titrations of too weakly acidic or basic substances are carried out using non-aqueous solvents so as to get sharp end point.

Such titrations can also be used for the titration of the substances not soluble in water.

The speed, precision and accuracy of the non-aqueous method are close to those of classical acidimetric and alkalimetric titrations.

Non-aqueous titrimetry

First reported successful quantitative titration of organic acid and base in non-aqueous solvent: 1910.

To an understanding of non-aqueous acid base titrimetry the theories of acid and base is very important. The theories are:

- Arrhenius acids and bases - Bronsted-Lowry acids and bases- Lewis acids and bases

Arrhenius acids and bases

Acids are hydrogen containing compounds

that dissociates to yield hydrogen ions (H+)

when dissolved in water.

Bases are compounds that dissociates to

yield hydroxide/hydroxyl ions (OH-) when

dissolved in water.

Arrhenius acids and bases

It has two major limitations. First, it was limited to water, or aqueous, solutions. Second, it practically limited acids and bases to ionic compounds that contained the H+ ion or the OH- ion.

Drawbacks:- Acids or bases must be dissociated or ionized- Didn’t explain, why CH4 contains H but not an acid?- Na2CO3 is basic but unable to donate OH-

Bronsted-Lowry theory The Bronsted-Lowry theory of acid and

base can be applied to reactions occurring during acid base titrations in non-aqueous solvents.

Acid: any substance, charged or uncharged which can donate proton.

Base: any substance, charged or uncharged which can accept a proton.

Acid: HA H+ + A-

Base: B + H+ BH+

An acid ‘HA’ dissociates to give a proton H+ and its conjugate base A-.

A base ‘B’ unite with a proton to produce its conjugate acid BH+.

Every base has its conjugate acid, just as an acid has its conjugate base.

According to this theory, an acid may be an

electrically neutral molecule (HCl), a positively

charged cation (C5H5NH+), or a negatively

charged anion (H2PO4-).

A base may be an electrically neutral molecule

(C5H5N) or an anion (Cl-).

Lewis acids and bases

The third theory of acids and bases was proposed by Gilbert Lewis.

Lewis focused on the donation or acceptance of a pair of electrons during a reaction.

This concept is more general than either the Arrhenius theory or the Bronsted-Lowry theory.

A Lewis acid is a substance that can accept a pair of electrons to form a covalent bond.

A Lewis base is a substance that can donate a pair of electrons to form a covalent bond.

A hydrogen ion (Bronsted-Lowry acid) can accept a pair of electrons in forming a bond. A hydrogen ion, therefore, is also a Lewis acid.

A Bronsted-Lowry base, or a substance that accepts a hydrogen ion, must have a pair of electrons available and is also a Lewis base.

An acid can only exhibit its acidic properties in the presence of base; conversely a base can only function as such in the presence of an acid.

The relative strengths of acids and bases are measured by the tendencies of these substances to give up or take on protons.

HCl is strong acid in water because it gives up its proton readily, where as acetic acid is weak acid since it relinquishes its proton to a small extent only.

Strength of acids and bases

Ionization of acids is less in an acidic solvent than in water. For example, hydrogen chloride is a weak acid when dissolved in acetic acid. This is because acetic acid is a much weaker base than water.

Compare this reaction with what happens when acetic acid is dissolved in the more acidic solvent like pure sulfuric acid.

The strength of an acid or base varies with the solvent or environment.

HCl behaves as a weak acid in glacial acetic acid whereas acetic acid is a strong acid in liquid ammonia.

Consequently, the strength of an acid depends not only on its own ability to release a proton, but also on the ability of the solvent to take up proton from acid.

SolventsThe ability of substances to act as acids &

bases will depend very much upon the nature of the solvent system which is employed.

Non-aqueous solvents are classified into

the 4 groups:

- Protophilic solvents- Protogenic solvents- Amphiprotic solvents- Aprotic solvents

Protophilic solventsPossess high affinity for protonWeak acids are normally used as soluteStrong protophilic solvents convert weak acid to strong acid-known as ’leveling effect’

Example: Liquid ammonia, amines, ether and ketones

HA + S SH+ + A-

Weak Acid (appeared as strong acid)

Basic solvent

Solvated proton

Conjugated base of acid

Weak acids are normally used in the

presence of strongly protophilic solvents as

their acidic strengths are then enhanced and

then become comparable to these of strong

acids; this is known as the leveling effect.

Protogenic solventsAcidic in natureReadily donates protonsStrong protogenic solvents increase the strength of weak basesSuch solvents exert a leveling effect on all bases dissolved in them

Example: Anhydrous acid like hydrogen fluoride & sulfuric acid

B + H+ BH+

Weak Base (appeared as strong

base)

From solvent

Conjugated acid of base

Amphiprotic solvents

Combine protogenic and protophilic properties of solventAble to both donate and accept proton

Example: Water, alcohol & weak organic acid

Acetic acid shows acidic property by releasing proton-

CH3COOH CH3COO- + H+

In presence of perchloric acid (strong acid) acetic acid shows basic property by accepting proton and produce ‘onium’ ion-

CH3COOH + HClO4 CH3COOH2+ + ClO4

-

‘onium’ ion

Aprotic solventsChemically neutral substancesVirtually un-reactiveDo not cause ionization of soluteNo reactions with acids and basesUsed to dilute reaction mixture

Example: Carbon tetrachloride, benzene, tolune.

In such a solution then, the actual titrating species is the ion CH3COOH2

+ which readily donates its proton to a base.

Theory of non-aqueous acid base titration

Water behaves both as a weak acid and a weak base thus in an aqueous environment it can compete effectively with very weak acids and weak bases with regard to proton donation and acceptance.

H2O + H+ H3O+ Compete with

RNH2 + H+ RNH3+

H2O + B OH- + BH+ Compete with

ROH + B RO- + BH+

Base

Acid

The effect of this is that the inflection in the titration curves for very weak acids and very weak bases is small, thus making end-point detection more difficult.

A general rule is that bases with pKa<7 (morphine, diazepam) or acids with pKa>7 (ascorbic acid, phenytoin) cannot be determine accurately in aqueous solution.

Various organic solvents may be used to replace the water since they compete less effectively with the analyte for proton donation and acceptance.

Fig. pKa values for some acidic and basic drugs.

Phenol (pKa= 9.9, Solubility in water: 8.3g/100ml at 20°C) , for example, cannot be titrated as an acid in aqueous solution because water is too acidic and present in too high a concentration to permit the phenolate ion to be formed by titration with the hydroxide ion.

Non-aqueous solvents also improve the solubility of many organic compounds. Many organic acids will dissolve more readily in methanol.

H++

Titration in non-aqueous solvents: Advantages1.1. Weak acids and weak bases give poor

end point during titration in aqueous solutions. Far more satisfactory end point found when titrations are carried out in non-aqueous media.

2.2. Many compounds are insoluble in water and soluble in organic solvent, thus permit their titration in non-aqueous media.

Non-aqueous titration of weak acids:Titrants:

There are several titrant available for the titration of acids:- Methoxides of the alkali metals (CH3ONa)

- Potassium hydroxide in methanol (KOH+CH3OH)

- Tetrabutyl ammonium hydroxide [CH3(CH2)3]4NOH

Methoxides of the alkali metals:

- These are most commonly used.- They are prepared by dissolving the

appropriate amount of alkali metal (Na, K, Li) in a mixture of benzene and methanol.

Preparation of a 0.1 N solution:

When metal has dissolved, have to add sufficient methanol until clear solution

Then add dry benzene slowly with continuous shaking until the solution appears cloudy

Repeat the addition of methanol followed by benzene until 1 liter clear solution has been prepared.

Mixture of 40 ml methanol and 50 ml dry benzene in Erlenmeyer flask

Add 4 gm of K or 2.3 gm of Na or 0.6 gm of Li to the flask (the metal should be freshly cut and have to add slowly)

1. Minimum amount of methanol have to use to ensure clear solution.

2. Have to store in sodium free glass.3.Have to protect it from atmospheric CO2.

Precaution:

Titrants are usually standardized by using reference standard- benzoic acid.

0.5% thymol blue in anhydrous methanol used as indicator.

Dimethylformamide used as solvent for the titration.

Standardization:

Burettes:

1. Titrant must be protected from atmosphere to obtain highest degree of precisions. It is preferable to store the titrant in a burette with a reservoir sufficiently large to contain 1 liter.

2. The reservoir is flushed out with nitrogen and a layer of nitrogen is laid over the titrant.

3. Teflon stopcocks can be used.

Apparatus:

Fig: Apparatus for the titration of weak acids

Burette

Titration vessel:

1. A three-necked flask would be ideal, as it provide an inlet and outlet for the used inert gas (nitrogen) as well as an opening to admit the burette tip.

A three-necked flask

2. An Erlenmeyer flask equipped with a rubber stopper which has been drilled to permit passage of the burette tip is satisfactory. A groove (channel) must be notched in the stopper to provide an air vent.

3. In all instances, an electromagnetic stirring apparatus is essential.

Solvents:

The solvents (protophilic solvents) most commonly employed in the titration of weak acids are-

Dimethylformamide O=CH-N(CH)3

n-butylaminePyridineEthylenediamine H2N-CH2-CH2-NH2

AcetoneMorpholine

Practical example:The titration of benzoic acid in n-butylamine by sodium methoxide.

C6H5COOH + CH3(CH2)3NH2 CH3(CH2)3NH3 + C6H5COO-+

CH3(CH2)3NH3 + CH3O- CH3OH + CH3(CH2)3NH2 +

C6H5COOH + CH3O- CH3OH + C6H5COO-

The titration is performed by the direct withdrawal of the proton from the benzoic acid by the methoxide.

Non-aqueous titration of weak basesTitrants:

Solutions of perchloric acid (HClO4) in either glacial acetic acid (CH3COOH) or dioxane are used almost exclusively for the titration of bases in non-aqueous titrimetry.

In glacial acetic acid, the titrating species will be onium ion.

CH3COOH + HClO4 CH3COOH2+ + ClO4

-

‘onium’ ion

O

OHClO4 +

O

OClO4 +

-

H+

Dioxane Mono-protonated dioxane

The usual concentration of titrant used is 0.1N to 0.05N. It may be diluted one (0.001N)

In dioxane, the titrating species will be mono- or diprotonated dioxane.

Apparatus:Burettes:

Having teflon stopcock are most suitable.Necessity of lubricating the teflon

stopcock is eliminated.Capacity of burette may be from 1ml to

10ml.

Titration vessels: It is not essential to protect the titration

from environment.So Erlenmeyer flasks or beakers may be

used.

Solvents:Glacial acetic acid alone, or Glacial acetic acid combined with aprotic solvent is commonly used. Aprotic solvents commonly used are chloroform, benzene.

Practical example: Titration of ephedrine alkaloid in glacial

acetic acid by acetous perchloric acid. Titration of ephedrine alkaloid by the

solutions of perchloric acid (HClO4) in dioxane. Here aprotic solvents are used as solvent.

See reactions and description Ref: Pharmaceutical chemistry by Chatten, Volume 1, pp 236-237

OH

N

H CH3

Ephedrine pKa = 9.6