5. non aqueous titrations

Learning objectives
Introduction
Types of solvents
Acidimetry in non aqueous medium
Alkalimetry in non aqueous medium
Estimation of Sodium benzoate and Ephedrine HCl
Applications of non aqueous titrations in pharmacy
Conclusion
Reference

1. Non-Aqueous titrations Prepared by G. Nikitha, M.Pharmacy Assistant Professor Department of Pharmaceutical Chemistry Sree Dattha Institute Of Pharmacy Hyderabad

2. contents Learning objectives Introduction Types of solvents Acidimetry in non aqueous medium Alkalimetry in non aqueous medium Estimation of Sodium benzoate and Ephedrine HCl Applications of non aqueous titrations in pharmacy Conclusion Reference

3. Learning objectives In these topic we will discuss about Brief introduction of Non aqueous titration, definition Indicators used in Non aqueous titration Applications of non aqueous titrations in pharmacy Acidimetry in non aqueous medium Alkalimetry in non aqueous medium Types of solvents Estimation of Sodium benzoate and Ephedrine HCl

4. introduction Non aqueous titration are those in which the titration of weakly acidic or basic substances are carried out using non aqueous solvents so as to get sharp end point. Such titrations are can also be used for the titration of substances not soluble in water. Before understanding the significance of the use of Non aqueous solvents some important terms and concepts have to understood. The reactions which occur in these Non aqueous solvents can be explain by using Lowry- Bronsted theory. Acid is a proton donor Base is a proton acceptor Example: Hcl H + +Cl HSO4 - H + + SO 4 2

5. Non aqueous titrations are simple and accurate. The apparatus needed have almost the same as that used in classical titrations expect with some precautions that moisture and carbon dioxide have to be excluded. In presence of moisture water, being weakly basic would compete with the week nitrogen base for HClO 4. H 2 O +HClO 4 H 3 O+ ClO 4 The sharpness of the end point may get lost. Moisture content in this non-aqueous titrimetry should be less than 0.05% Organic acids or bases that have been insoluble in water can be made to dissolve in Non aqueous solvents and titrated.

6. The neutralization of a base with standard acid in non-aqueous titrimetry may be put as fallows BOH +CH 3 ONa BONa +CH 3 OH A greater difference in the protophilic properties of various substances takes place in non aqueous solution such as acetonitrile, acetone and dimethyl formamide than in aqueous solutions due to the leveling effect of water. Although the following acids have been of about equal strength in aqueous solvents acidity has been found to decrease in the following order: HClO 4 >  H 2 SO 4 > HCl >HNO 3

7. Indicators In non-aqueous titrations the end point can located by the colour changes of this suitable indicator. Few indicators used in non-aqueous titrations are given below. Indicator Basic Neutral Acids 1. Crystal violet Voilet Blue-Green Yellowish green 2. Naphtolbenzene Blue or Green Orange Dark Green 3. Oracet Blue B Blue Purple Pink 4. Quinaldine Red Magneta ------- Almost colourless

8. Types of solvents Solvents are classified according to their properties as fallows 1. Aprotic solvents 2. Protogenic solvents 3. Protophilic solvents 4. Amphiprotic solvents

9. 1. Aprotic solvents: These are solvents which are chemically inert and are not involved in any chemical reaction. Example: Chloroform, Benzene. 2. Protogenic solvents: These are acidic substances and yield protons. Example: sulphuric acid, Hydrochloric acid, Nitric acid etc

10. 3. Protophilic solvents: These solvents are of two types. They are strongly basic or weakly basic in nature. A strongly basic solvent has stronger tendency to accept the proton. A weekly basic solvent has weaker tendency to accept the proton. A strongly basic solvents is called as a “Leveling solvent” (for weak and strong acids) because it can abstract proton from any acid. Whether it is strong acid or weak acid. This effect is called “Leveling effect”. As it does not differentiate between strong or weak acid. On the other hand a weakly basic solvent has weak tendency to accept the proton. Hence this solvent is tendency to accept the proton called a “ Differentiating solvent” . Because it can abstract proton from strongly acidic substances and from weak acids. This effect is called “ Differentiating effect”. Differentiating solvents are not useful in non-aqueous titrations.

11. Similarly strongly acidic solvents are leveling solvents for weak bases and strong bases. strongly acidic solvents can donate proton to strong bases as well as weak bases. Example: Perchloric acid, acetic acid etc. 4. Amphiprotic solvents: These have both protogenic and protophillic properties Example: water, acetic acid, alcohols. Water has both protogenic and protophillic properties. It can behave as a base or acid.

12. Acedimetry in non-aqueous medium It used for the quantitative estimation of weak base. Titrant : Titrant should be strongly acidic in nature. It is the known concentration. It should be taken in burette Example: Perchloric acid Titrate: Titrate should be weakly basic in nature It is u n known concentration . It should be taken in conical flask Example: alkali salts of organic acids, amines, heterocyclic nitrogen compounds are analyzed. Drugs : Ephedrine, Morphine, Acyclovir, caffeine etc.

13. Solvents: The solvents are either neutral such as alcohol, chloroform, benzene etc or acidic solvents such as acetic acid etc. solvents should be protogenic in nature. Indicator: Crystal violet, Quinoline red, thymol blue.

14. Reactions: B+CH 3 COOH   ⇌   BH + +CH 3 COO Here B= Base CH 3 COOH= Acetic acid BH + = conjugate acid of base CH 3 COO = conjugate base Titrant reacts with the solvent and gets promoted as follows HClO 4 +CH 3 COOH ⇌ CH 3 COO H 2 +ClO 4 - Here HClO 4 =   Perchloric Acid CH 3 COOH= Acetic acid ClO 4 - = Perchlorate

15. Titration reaction with conjugate base anion may be put as follows CH 3 COO + CH 3 COO H 2 ⇌ 2 CH 3 COOH So overall reaction may be put as follows: B+HClO 4 BH + +ClO 4 -

16. Preparation of 0.1 N perchloric acid : 8.5 ml of perchloric acid + 500ml of glacial acetic acid + 30ml of acetic anhydrous cooled and volume is made up to 1000ml with glacial acetic acid It is kept for a day for the excess acetic acid anhydride to combine with water present The molecular weight of the perchloric acid is 100.46. So 1 liter of 0.1N solution can be prepared by using 10.046g

17. Standardization of 0.1 N perchloric acid: 700mg of potassium hydrogen phthalate + 500ml of glacial acetic acid In 250 ml flask To these 2 drops of crystal violet is added This solution is titrated with perchloric acid Untill the violet colour changes to emerald green violet emerald green

18. potassium hydrogen phthalate is reacted with perchloric acid to get Phthalic acid and potassium perchlorate . Here Potassium (K) from potassium hydrogen phthalate is removed and replaced with hydrogen (H) from perchloric acid . 1ml of 0.1N HClO 4 ≡ 20.48 mg of C 8 H 5 KO 4

19. Assay of Ephedrine Hydrochloride: An accurate weight of the sample + glacial acetic acid + Mercuric acetate Titrated with 0.1N perchloric acid Using crystal violet as indicator

20. Estimation of Ephedrine: An accurate weight of the sample + glacial acetic acid Titrated with 0.1N perchloric acid Using crystal violet as indicator

21. Estimation of Sodium benzoate Preparation of 0.1N solution of HClO4 and its standardization : 8.5 ml of perchloric acid + 500ml of glacial acetic acid + 30ml of acetic anhydrous cooled and volume is made up to 1000ml with glacial acetic acid It is kept for a day for the excess acetic acid anhydride to combine with water present The molecular weight of the perchloric acid is 100.46. So 1 liter of 0.1N solution can be prepared by using 10.046g

22. Standardization of 0.1 N perchloric acid: 500mg of potassium hydrogen phthalate + 25ml of glacial acetic acid In 250 ml flask To these 2 drops of crystal violet is added This solution is titrated with perchloric acid Untill the blue colour changes to blue green blue blue green

23. Assay Procedure : Weigh accurately about 0.25 g of Sodium Benzoate +20 ml of anhydrous glacial acetic acid warming to 50º if necessary, cool Titrate with 0.1 M perchloric acid, using 0.05 ml of 1-naphtholbenzein solution as indicator. Carry out a blank titration.

24. Alkalimetry in non-aqueous medium It used for the quantitative estimation of weak acid. Titrant : Titrant should be strongly basic in nature. It is the known concentration. It should be taken in burette Example : sodium methoxide , Lithium methoxide , sodium amino methoxide , sodium triphenyl methane Titrate: Titrate should be weakly acidic in nature It is unknown concentration. It should be taken in conical flask Example : Benzoic acid etc Drugs : Nalidix acid, Acetazolamide , Allopurine , Mercaptopurine etc

25. Solvents: Dimethyl Formamide (DMF), Pyridine, ethylene diamine etc. Strong basic solvents such as butyl amine, morpholine used for the titration of weak acids. Indicator: Thymol blue

26. Preparation and standardization of 0.1N sodium Methoxide Preparation: 2.5g of freshly cut sodium metal + 150 ml of ice cold methanol Present in one liter of volumetric flask When sodium metal gets dissolved, Sufficient quantity of benzene is added to make the volume up to 1 liter.

27. standardization of 0.1N sodium Methoxide 400mg of benzoic acid +80m of Dimethyl Formamide (DMF) In a flask 3 drops of thymol blue is added Titrated with sodium methoxide End point is blue colour

28. Assay of Benzoic acid: Required quantity of Benzoic acid + butylamine Titrated with sodium methoxide thymol blue as indicator End point is blue colour

29. applications It is useful for the titrations of weak acids or weak bases. It is simple, qualitative and selective method. It can be used for titration of mixture of acids as well. Many organic acids which are not soluble in water can be dissolved in non aqueous solvents

30. Conclusion In these topic we have discussed about Brief introduction of Non aqueous titration, definition Indicators used in Non aqueous titration Applications of non aqueous titrations in pharmacy Acidimetry in non aqueous medium Alkalimetry in non aqueous medium Types of solvents Estimation of Sodium benzoate and Ephedrine HCl

31. Reference Pharmaceutical Chemistry -Inorganic Volume-1 by G. R. Chatwal . Essentials of Inorganic Chemistry by Katja A. Strohfeldt . Indian Pharmacopoeia. M.L Schroff , Inorganic Pharmaceutical Chemistry. P. GunduRao , Inorganic Pharmaceutical Chemistry, 3rd Edition A.I. Vogel, Text Book of Quantitative Inorganic analysis. Bentley and Driver's Textbook of Pharmaceutical Chemistry .

32. Thank you