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1. B Pharmacy I st sem BP102T: Pharmaceutical Analysis-I Precipitation titrations 24-02-2022 1

2. SCOPE This course deals with the fundamentals of analytical chemistry, various techniques of analysis, principles of electrochemical analysis of drugs and their role in chemical research. This lecture basically focuses on precipitation titration. 24-02-2022 2

3. OBJECTIVES Upon completion of this lecture you will be able to: 1. Know the concept of precipitation titration 2. Know about various methods involved in precipitation titration. 3. Know about various application of precipitation titrations. 24-02-2022 3

4. CON TENTS Introduction General principle and theory Mohr’s Method Volhard’s Method Fajan’s Method Applications 24-02-2022 4

5. Introduction Precipitation is the process in which there is combination of ionic species to form insoluble product. This product is called as precipitate or phenomenon is precipitation. These precipitation titrations involves formation of precipitate at equivalence point which indicate completion of the reaction. It is also known as argentometric titration. Ideal properties of precipitation titrations : The precipitate must be insoluble in the liquid. The process of precipitation should be rapid. 24-02-2022 5

6. The titration results should not be affected by adsorption problems. It should be easy to detect the end point during the titration. The indicator must be suitable to determine the end point. The choice of precipitating agent should depend upon solubility of the drug inside the solvent used. One of the main reasons for the limited use of such titrations is the lack of suitable indicators to detect the end point. 24-02-2022 6

7. Theory The precipitation of many products occurs mainly due to solubility. The solute molecules are held together by inter molecular forces of attraction. In order to dissolve a solid, these forces of attraction must be overcome so that solute-solute attraction is replaced by solute-solvent attraction. The solvent should compete with crystal forces and overcome them, which often means that the solvent environment must be similar to that provided by the crystalline structure. During precipitation, the inter molecular forces between the molecules of the product are high and solute-solute forces replace the solute –solvent forces. 24-02-2022 7

8. The solubility mainly depends upon several factors such as ions, pH, temperature and solvents etc. Common ion effect: The solubility of any slightly soluble salt can be decreased by adding an excess of either of its ions. Ex.- The dissociation of a slightly soluble salt BA is BA (S) ⇌ B + + A - At equilibrium, Ksp = [B + ] [A - ] Ksp = Solubility product which is a constant 24-02-2022 8

9. If, an excess of either B + or A - ions are added in the form of another salt (whose solubility is greater than that of BA), then the product of ionic concentrations [B + ] [A - ] will exceed the solubility product and hence BA will precipitate, The common ion effect provides a valuable method for controlling (the concentration of the ions furnished by a weak electrolyte. Effect of pH in solubility : The solubility of a salt will be decreased by an increase in pH and vice versa and mainly depends on the anion of the salt and it is a conjugate base of a weak acid or cation which is conjugate acid of a weak base. 24-02-2022 9

10. Effect of temperature on solubility : The solubility of the precipitate increases with the rise in temperature. The influence of temperature is small in case of some substances, but with some substances it is quite appreciable. The solubility of AgCl at 10°C and 100°C is 1.72 and 21.1 mg / lit., while that of BaSo 4 is 2.2 and 3.9 mg/lit. respectively. Effect of the solvent upon the solubility : The solubility of most inorganic compounds is reduced by the addition of organic solvents such as alcohols. Ex : The addition of above 20% by volume of ethanol renders the solubility of lead sulphate practically negligible, thus permitting quantitative separation 24-02-2022 10

11. Determination of end point Mohr’s method- depends upon formation of colored precipitate. Volhard’s method- depends upon formation of soluble colored compound or colored complex ions (colored solution). Fajan’s method- depends on the formation of colored adsorption compound. 24-02-2022 11 According to the method of detection of endpoint, precipitation titration is classified into 3 main types:

12. Principle : It is one of the important precipitation method used for quantitative determination of halide ion. It was developed by Mohr in 1856. Silver nitrate is used as precipitated agent to precipitate the analyte chloride ion (Cl - ). Chromate solution (CrO 4 -2 ) is used as indicator to determine the end point. The end point is activated when there is appearance of brick red precipitate of silver chromate. The following reaction takes place AgNO 3  Ag + + NO 3 - 24-02-2022 12 Mohr’s Method

13. Ag + + Cl -  AgCl (Ppt.) 2Ag + + CrO 4 -2  Ag 2 CrO 4 (ppt.) Firstly silver ions combine to chloride ions to form highly insoluble AgCl precipitation. When all chloride ions consumed then excess silver ions will react with chromate to form silver chromates. First of all AgCl precipitation occurs, sometimes even though silver chromates appears then it immediately converts to AgCl. Ag 2 CrO 4 + 2 Cl -  2 AgCl + CrO 4 -2 When the whole of chloride has been used up, silver chromate will be formed and brick red coloration or precipitate will appear. 24-02-2022 13

14. Procedure Dissolve 1.69 g AgNO 3 in little amount of distilled water. When it dissolves completely then make it up to 100 mL with distilled water. It will produce 0.1 N AgNO 3 Solution. Consider that we have to determine the concentration of Cl - in a sample NaCl or KCl. For this weigh accurately 1.2 g of NaCl or 1.6 g of KCl and dissolve in distilled water and make it up to 250 mL with distilled water. Transfer 50 mL of Chloride solution into conical flask & add 2 mL of potassium chromate solution as indicator. Fill the burette with 0.1 N AgNO 3 Solution. 24-02-2022 14

15. Now start the titration by drop wise addition of AgNO 3 from burette with continuous shaking of conical flask. A time will reach when a brick red color of non uniform intensity will produce. Continue the titration till uniform brick red color is produced. Note the reading as this end point. Perform blank titration and subtract the blank volume from the previous volume. To check the quantity of Cl - ions 1mL of 0.1 N AgNO 3 is equivalent to 0.003558 g of Chloride. 24-02-2022 15

16. Main features of Mohr’s Method 24-02-2022 16 Sample Cl - , Br - (Not for I - or SCN - ) Type of titration Direct titration pH Neutral or slightly alkaline Indicator Potassium Chromate Standard solution Standard AgNO 3 Color at end point Brick red color

17. Limitations 1. pH - Mohr method should be done in neutral or slightly alkaline medium (pH= 6.5-9) because: At acidic pH : The chromate ion changes into acid chromate (HCrO 4 - ) and then to dichromate (Cr 2 O 7 - ). Both these form soluble salts with silver ions and so no colored ppt will formed at the end point. To overcome this sufficient CaCO 3 is added to neutralize it. At basic pH (>9) : If the solution is basic, then the AgNO 3 forms silver hydroxide. To overcome this dil. nitric acid is added to neutralize it. Ag + + OH - AgOH (Silver hydroxide) 24-02-2022 17

18. This method is not suitable for iodides because the color of precipitate of AgI is similar to potassium chromate solution. Due to this end point detection is difficult to recognize. For titrating chlorides and bromides of barium, the solution is treated with a slight excess of potassium sulphate. This is due to the insoluble nature of barium sulphate than silver chromate and will be precipitated earlier. Silver chromate is more soluble than silver chloride so that no silver chromate be precipitated until all Cl - ions have been precipitated as AgCl provided that the CrO 4 - conc. should be adjusted to make silver chromate formed only at the end point and so prevent error in the end point. 1 ml of 5% K 2 CrO 4 solution is suitable. 24-02-2022 18

19. Applications Some of the important drugs determine by this method are NaCl and dextrose injection. Used for estimation of Cl - in body fluids. Used for estimation of Chromate ion It is useful for estimation of NaCl and KCl in electrolytic combination. 24-02-2022 19

20. Volhard’s Method It was developed by Volhard in 1874. It was developed for estimation of silver in the presence of dil. HNO 3 by titrating against standard thiocyanate (SCN) solution in presence of ferric salt as indicator (ferric alum). It is carried out in acidic medium in order to prevent the hydrolysis of ferric ion. Volhard, a process for assessing chlorine, bromine, and iodine in the form of halides by precipitating them with excess silver nitrate and using a thiocyanate solution to titrate excess. 24-02-2022 20

21. Principle : Analyte is treated with the measured excess of Silver nitrate: X - + Ag + AgX + Ag + (excess) The unreacted Silver ions are titrated with a standard solution of Thiocyanate ion, using Fe(III) as indicator: Ag + + SCN - AgSCN When all the silver has been consumed then upon further addition of SCN, reaction takes place between ferric ion and SCN ions to form red colored ferric thiocyanate complex. Fe 3+ + 3SCN - Fe(SCN) 3 (red color) The formation of red color complex denotes the end point.   24-02-2022 21

22. Preparation of 0.1 N AgNO 3 solution Dissolve 1.69 g AgNO 3 in little amount of distilled water. When it dissolves completely then make it up to 100 mL with distilled water. It will produce 0.1 N AgNO 3 Solution. Preparation of 0.1 N KSCN solution Weigh accurately 0.97 g KSCN and dilute upto 100 mL with distilled water. Procedure Fill the burette with KSCN solution. Transfer 25 mL or excess of 0.1 N AgNO 3 solution into conical flask and add 10 mL of dil. HNO 3 solution. Now add 1 mL of ferric salt to conical flask & titrate the contents with titrant (KSCN) from burette. 24-02-2022 22

23. Add few mL of nitrobenzene to prevent the interference with chloride impurities. When there is permanent appearance of red color then stop the titration & note the reading. Perform blank titration and subtract the blank volume from the previous volume and calculate the conc. of Ag + present in the sample. Calculate the percentage of silver in the sample 1mL of 0.1 N KSCN is equivalent to 0.0108 g of Silver.   24-02-2022 23

24. Main features of Volhard’s Method 24-02-2022 24 Sample All halogens and thiocyanates Type of titration Indirect titration pH Acidic pH Indicator Iron(III) alum Standard solution Ammonium thiocyanate Color at end point Appearance of red complex with Fe 3+ ions The Volhard method is an indirect or back titration method in which an excess of a standard solution of silver nitrate is added to a chloride containing sample solution. The excess silver is then back titrated using a standardized solution of potassium or ammonium thiocyanate with ferric ion as an indicator. The amount of silver that is precipitated with chloride in the sample solution is calculated by subtracting the excess silver from the original silver content.

25. Modified Volhard’s method When chlorides are analyzed, the Volhard method has to be slightly modified. During titration, the solution is in contact with two precipitates simultaneously AgCl and AgSCN , which have different solubility ( AgSCN is less soluble than AgCl). So, after titration, the excess SCN- ions react with the AgCl in precipitate, and the red color of the iron-thiocyanate complex gradually disappears. Addition of next portion of SCN- restores it, but after short time the process repeats. This could lead to huge error in analysis. 24-02-2022 25

26. To avoid this, before titration with thiocyanates, add a solution of few mL of an organic liquid (chloroform, nitrobenzene etc.) which does not mix with water. This compound will moisten the surface of the precipitate forming on it a film (layer) insoluble in water and thus isolating it from the solution. This effectively prevents any exchange of ions between precipitate and solution. Limitations of Volhard's method Can not be used where the solution has to be neutral. Time consuming 24-02-2022 26

27. Applications Sulphanomide derivatives can be assayed by Volhard method. This method has applications in estimation of ferric ions in haematinics. Modified volhard’s method can be used for estimating following drugs a) Aminophylline ( Bronchodilator) b) Aminophylline injection c) Aminophylline tablet d) NaCl injection.   24-02-2022 27

28. Fajan’s Method It was developed by Fajan in 1923 -1924. This method employs adsorption indicator for detection of end point. Principle : The action of adsorption indicator is based upon the fact that at the end point, the indicator get adsorbed on the surface of the precipitate and there is color change. Various indicators like flourescein, Eosin, Dichlorofluorscein can be used to detect the end point. Mechanism of Adsorption : Let us consider the titration between sodium chloride and silver nitrate. When a Cl - salt reacts with Ag + ions there is formation of insoluble AgCl precipitates. The ions surrounding the layer of precipitate constitute primary adsorbed layer. 24-02-2022 28

29. As the precipitation proceeds & reaches near completion. There is decrease in Cl - ions concentration & the ion in the primary layer are replaced by opposite charges. The newly formed layer is called as secondary adsorbed layer. When all the Cl - ions has been converted to AgCl then the indicator gets adsorbed to secondary layer and causes color change. This point is called end point. 24-02-2022 29

30. Procedure Prepare 0.1 N standard NaCl solution. Prepare 0.1 N AgNO 3 solution and fill it with burette. Transfer 25 mL of 0.1 N NaCl standard solution to a conical flask and add 10 drops of fluorescein indicator. Add 0.1 g dextrin to prevent the coagulation of AgCl. Now start the titration by drop wise addition of AgNO 3 solution from burette and continue till the color changes from yellow to pink. Repeat the titration for 3 times and calculate the average value & then determine the conc. of Cl - ion and exact normality of AgNO 3. 24-02-2022 30

31. 24-02-2022 31 Main features of Fajan’s Method 24-02-2022 31 Sample Cl - , Br - Type of titration Direct titration pH Neutral Indicator Dichlorofluorescein (Adsorption indicator) Standard solution Standard AgNO 3 Color at end point Appearance of pink color

32. Indicators used in Fajan’s method Name of indicator Experimental conditions Color change at end point Dichlorofluorescein pH range 4.4 to 7 Yellow green to red Tartrazine Back titration Colorless to green Fluorescein Neutral or weakly basic solution Yellow green to pink Tetrabromo fluorescein Ethanoic acid solution Pink to red violet 24-02-2022 32

33. Limitations Low background levels of non-reacting ions to ensure that coagulation does not occur. Will not work with very low levels as there will not be enough precipitate to allow the color change to be observed. Method is pH dependent as the indicator must be in the ionized form. 24-02-2022 33

34. Applications It is used for the estimation of NaCl It is also used for the estimation of Cl - ion in binary mixtures & biological fluids. It is also used for standardization of AgNO 3 solution. Estimation of NaCl Estimation of NaCl ( Sodium chloride) or Assay of Sodium chloride can be done by Mohr’s Method or Fajan’s Method ( Here you can write any one method either Mohr’s or Fajan’s method ). 24-02-2022 34

35. Comparison of silver titration methods 24-02-2022 35 Method Advantages Disadvantages Mohr’s Simple For alkaline solutions only Not suitable for iodides Volhard’s Capable of direct silver and indirect halide analyses Very clear color change Must be 1M nitric acid solution. Some problems with specific ions. Modified Volhard’s It minimize the error occurred in Volhard’s method due to the addition of nitrobenzene solution Must be 1M nitric acid solution. Fajan’s Capability for different pH ranges and selectivity with different indicators Difficulty with dilute solutions Should not be a high background ionic level.

36. References 1. G. Vidyasagar “Text Book of Pharmaceutical Analysis”, Kalyani publishers, Vol 1, I st edition, 2005, Page no. 93-101 2. R. M Verma Textbook of Analytical Chemistry, CBS Publishers, 3 rd edition, 2008 3. Ashutosh Kar “ Pharmaceutical Analysis” CBS Publishers, Volume 1, I st edition, 2010 24-02-2022 36

37. Questions 24-02-2022 37 What is precipitation titration? Give the ideal characteristics for precipitation titration. Describe in detail the influence of a) Acid b) Temperature c) Solvent Explain in detailed about the following precipitation reactions, namely i) Volhard’s method ii) Mohr’s method iii) Fajan’s method 5. Enumerate the limitations of mohr’s method. 6. Write down the applications of precipitation titrations.