NON AQUEOUS TITRATION

INTRODUCTION

• Non- aqueous titrations are the titrations in which weakly acidic or basic substances are carried out using non–aqueous solvents to get sharp end point.

• The moisture content in non–aqueous titrations should not be more than 0.05%.

• Moisture and carbon dioxide are to be avoided in non– aqueous methods

THEORY

• Lowry-Bronsted theory

HB ↔ H+ + B- (ACID) (CONJUGATE BASE)

B + H+ ↔ HB+ (BASE) (CONJUGATE ACID)

• The ability of substances to act as acids or bases depend on the choice of solvent system.

SOLVENTS

• Protogenic solvents: on dissociation yield a H+

Ex:H2SO4,,CH3COOH

• Protophilic Solvents: high affinity for H+

Ex:(CH3CO)2O,ether,pyridine• Amphiprotic Solvents : donate protons and accept

protons

Ex:H2O,alcohols• Aprotic Solvents: no tendency to yield and accept H+

Ex:CCl4,hydrocarbons

ASSAY BY NON-AQUEOUS

TITRATIONS• Acidimetry in Non-aqueous Titrations—It can

be further sub-divided into two heads, namely :

(i) Titration of primary, secondary and tertiary amines, and

(ii) Titration of halogen acid salts of bases.

• Alkalimetry in Non-aqueous Titrations— titration of acidic substances

ACIDIMETRY IN NON AQUEOUS TITRATIONS

Example : Primary amines

METHODOLOGY: four steps

• (i) Preparation of 0.1 N Perchloric acid,

• (ii) Standardization of 0.1 N Perchloric Acid,

• (iii) Choice of Indicators, and

• (iv) Effect of Temperature on Assays

PREPARATION OF 0.1 N PERCHLORIC ACID

• Materials Required : 8.5 ml of perchloric acid (70.0 to 72.0%) ; 1 Litre of glacial acetic acid ; 30ml of acetic anhydride.

• Procedure : Gradually mix 8.5 ml of perchloric acid to 900 ml of glacial acetic acid with vigorous and continuous stirring. Now add 30 ml acetic anhydride and make up the volume to 1 litre with glacialacetic acid and allow to stand for 24 hours before use.

• The acetic anhydride reacts with the water (approx. 30%) in perchloric acid and some traces in glacialacetic acid thereby making the resulting mixture practically anhydrous. Thus, we have :

H2O + (CH3CO)2O → 2CH3COOH Acetic anhydride Acetic acid

STANDARDIZATION OF 0.1 N PERCHLORIC ACID

• Weigh accurately about 0.5 g of potassium hydrogen phthalate in a 100 ml conical flask.

• Add 25 ml of glacial acetic acid and attach a reflux condenser fitted with a silica-gel drying tube. Warm until

the salt gets dissolved completely. Cool and titrate with 0.1 N perchloric acid by making use of either of

the following two indicators :• (a) acetous crystal violet-2 drops, end point Blue to Blue-

Green (0.5% w/v)• (b) acetous oracet blue B-2 drops, end point Blue to Pink.

REACTIONS

RCOOM RCOO– + M+

CH3COOH2++RCOO– RCOOH+ CH3COOH

Onium ion Acetic acid

KHC8H4O4 + HClO4 C8H6O4+KClO4

POTTASSIUM HYDROGEN PTHALTE PTHALIC ACID

204.14 g C8H5O4K ≡ HClO4 ≡ 1000 ml N

or 0.02041 g of C8H5O4K ≡ 1 ml of 0.1 N HClO4

Strength of 0.1N Perchloric acid = wt. of potassium hydrogen phthalate taken

____________________________________

Vol. of Perchloric acid X 0.02042

CHOICE OF INDICATORSS.No. Name of Indicator Colorchang

e

Basic

Observed

Neutral

Acidic

1

2

3

4

Crystal violet (0.5% w/v in glacial acetic acid)

Oracet Blue B(0.5% in glacial acetic acid)

α-Naphtholbenzein

(0.2% in glacial acetic acid

Quinalidine Red

(0.1% in methanol

Violet

Blue

Blue

Magenta

Bluish green

Purple

Orange

—

Yellowish green

Pink

Dark-green

Almost colourless

EFFECT OF TEMPERATURE ON ASSAYS

• Non-aqueous solvents possess greater coefficients of expansion as compared to water, so there is effect of temperature.

• The volume of titrant may be corrected by the application of the following formula :

Vc = V [1 + 0.001 (tl + t2)]

Vc = Corrected volume of titrant,

V = Volume of titrant measured,

tl = Temperature at which titrant was standardized,

t2 = Temperature at which titration was performed.

Titration of primary amines

• Ex: Methlyldopa R.NH2 + HClO4 → [R.NH3]+ + ClO4

-

• Specific reaction between methyldopa and perchloric acid is expressed by the following equation

• Materials Required : Methyldopa 0.2 g ; anhydrous formic acid : 15 ml ; glacial acetic acid : 30 ml ;dioxane : 30 ml ; 0.1 N perchloric acid and crystal violet solution.

• Procedure : Weigh accurately about 0.2 g and dissolve in 15 ml of anhydrous formic acid, 30 ml of glacial acetic acid and 30 ml of dioxane. Add 0.1 ml of crystal violet solution and titrate with 0.1 N perchloric acid. Perform a blank determination and make any necessary correction.

Calculations

211.24 g of Cl0Hl3NO4 ≡ HClO4

or 0.02112 g C10H13NO4 ≡ 1 ml of 0.1 N HClO4

• The percentage of methyldopa present in the sample is given by :

% Methyldopa = ml × 0.1 × 0.02112× 100

wt. of sample

PRECAUTIONS

(a) Perchloric acid is usually available as a 70 to 72% mixture with water .It usually undergoes a spontaneous explosive decomposition and, therefore, it is available always in the form of a solution.

(b) Conversion of acetic anhydride to acetic acid requires 40-45 minutes for its completion. It being an exothermic reaction, the solution must be allowed to cool to room temperature before adding glacial acetic acid to volume,

(c) Avoid adding an excess of acetic anhydride especially when primary and secondary amines are to be assayed, because these may be converted rapidly to their corresponding acetylated non-basic products :

R—NH2 + (CH3CO)2O → R.NH.(CH3CO) + CH3COOH Primary amine Acetylated product

(d) Perchloric acid is not only a powerful oxidising agent but also a strong acid. Hence, it must be handled very carefully.

ADVANTAGES OF NON AQUEOUS TITRATIONS

• 1) Organic acids and bases that are insoluble in water are soluble in non-aqueous solvent.

• 2) Organic acid, which is of comparable strength to water, can be titrated easily in non-aqueous solvent. Bases also follow the same rules.

• 3) A non-aqueous solvent may help two are more acids in mixture. The individual acid can give separate end point in different solvent.

• 4) By the proper choice of the solvents or indicator, the biological ingredients of a substance whether acidic or basic can be selectively titrated.

• 5) Non aqueous titrations are simple and accurate, examples of non aqueous titration are: Ephedrine preparations, codeine phosphate in APC, tetracycline, teramycin, Antihistamines and various piperazine preparations.

OTHER EXAMPLES

S.No. Name of Substance Indicator Employed

1

2

3

4

5

Amantadine

hydrochloride

Chlorpromazine

hydrochloride

Clonidine hydrochloride

Cyproheptadiene.HCl

Ephedrinehydrochloride

Crystal violet

Methyl orange

α -Naphthol benzein

Crystal violet -do-

S.No. Name of Substance Indicator Employed

1

2

3

4

5

6

Acetazolamide

Bendrofluazide

Allopurinol

Mercaptopurine

Amylobarbitone

Nalidixic acid

Potentiometric determination

Azo violet

Thymol blue

-do-

Quinaldine Red

Thymolphthalein