6. COMPLEXOMETRIC TITRATION.pptx

Complexometric titration for Pharm D 1st year and B pharmacy

1. COMPLEXOMETRIC TITRATION NITIN SOLANKI School of pharmacy R K UNIVERSITY rajkot

2. CONTENTS INTRODUCTION CONCEPT OF COMPLEXATION AND CHELATION CLASSIFICATION OF COMPLEXOMETRIC TITRATIONS METAL ION INDICATORS MASKING AND DEMASKING AGENTS STANDARDISATION OF DISODIUM ETHYLENEDIAMINE TETRA ACETATE ESTIMATION OF MAGNESIUM SULPHATE ESTIMATION OF CALCIUM GLUCONATE

3. 1. INTRODUCTION Complexometric titration involves titration between metal ions and complexing agent or chelating agent (Ligand). This titration is based on the analytical mechanism of a complexation reaction. In this method, an ion is changed into a complex ion and the equivalence point is determined with the help of metal indicators or electrometrically. An EDTA (disodium edetate ) is a popular complexing agent or chilon . The chilons react with metal ions to form a special type of complex known as chelate.

4. 2. CONCEPT OF COMPLEXATION AND CHELATION According to the International Union of Pure and Applied Chemistry (IUPAC), " chelation involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central atom". These ligands are organic compounds called chelating agents , chelants , chelators or sequestering agents . Chelates are also called electron donating ion or molecule which can form one or more covalent or co-ordinate bonds with metal ions. The complex are formed by the reaction of a metal ion with an anion or a neutral molecule or a positive ion very rarely. The complex formed differs in properties from that of metal ion. The groups attached to the central cation or a metal is called a ligand.

5. Complexing agent forming a single bond is called unidentate and called as a co-ordination compound. If complexing agent forms more than one bond with the polyvalent ion, then is said to be polydentate ligand and called as chelating ligand. If complex formed between complexing agent and metal is soluble in water, it is called as sequestering agent. Complexing agents are of different types: Neutral molecules: Neutral molecules having lone pair of electron also act as complexing agent. Example: Ammonia forms cuprammonium complex with copper [Cu(NH3)4]2+. Groups whose proton can be easily replaced such as —COOH, phenolic, and enolic OH. Sequestring agents having groups like COOH, SO3H, NH2 and OH. Example of chelating agents: Dimethylglyoxime and salicylaldoxime Example of sequestering agents: Ethylene Diamine Tetra Acetic Acid (EDTA)

6. 3.CLASSIFICATION OF COMPLEXOMETRIC TITRATIONS Direct Titration Back Titration Replacement Titrations Alkalimetric titrations of metals Indirect titration

7. Direct Titration In this type of titrations, the sample solution of metal ion, in the presence of a suitable buffer, is titrated against standard disodium edetate solution. Metal indicators such as Mordant red 7 are used in these titrations which show change in colour at the end point. Precipitation of metal hydroxide is prevented by adding some auxiliary complexing agent. At the equivalence point the concentration of metal ion decreases abruptly. A blank titration is also carried out using the blank solution without adding analyte . Blank titration is one in which all the components of the main titration are added but analyte is not added. The volume of edetate consumed in the blank titration is subtracted from the original estimation. Examples of substances estimated by direct titrations: Magnesium salts such as magnesium carbonate, bismuth salts such as bismuth nitrate, calcium salts such as calcium chloride, zinc salts such as zinc oxide etc.

8. Back Titration Sometimes direct titration is not possible because of various reasons such as:- Insolubility of substance e.g. lead sulphate , calcium oxalate. Stability of complex being very low. Precipitation of metal hydroxide in alkaline solution of buffer. Due to slow reactivity with the sodium edetate . For above problems back titration is a method of choice, in this titration, A known excess of disodium edetate along with buffer solution and indicator solution is added. Heating of the solution is done which promotes complex formation. Then it is cooled and excess edetate is back titrated using magnesium sulphate or zinc sulphate . Example of substances which are back titrated: Aluminium hydroxide gel, Dried Aluminium hydroxide gel, Calcium Phosphate

9. Replacement Titrations When back titration and direct titration is not possible because of end point not being sharp enough. Then the replacement titration is a method of choice. In this, determination of metal ion is done by displacing magnesium or zinc ions from EDTA complex with equivalent amount of metal ion and then liberated Magnesium or Zinc ions are titrated against edetate . Example: Calcium salt is determined in this way. In this, add standard volume of Magnesium-EDTA solution to calcium salt in the presence of buffer. Calcium displaces magnesium or zinc ion and form a stable complex with EDTA as calcium-EDTA. The displaced and liberated magnesium ions are then titrated with standard EDTA solution using Mordant black as indicator. Ca 2+ + Mg-EDTA -> Ca-EDTA Mg 2+ + EDTA 2- -> Mg-EDTA Cadmium, Lead and mercury can also be determined by this titration.

10. Alkalimetric titrations of metals Metal-EDTA complex formation reaction explains that protons are liberated from disodium edetate leading to formation of acid. M + + H 4 Y -4 MY + 4H + The acid that is formed can be titrated against a standard alkali but in an unbuffered solution. End point detection can be done by using acid base visual indicator or potentiometric method of detecting end point. Neutralization of the solution of metal has to be done before carrying out this titration.

11. Indirect titration Indirect determination of the certain organic substances can be made by adopting complexometric method. Mostly in this type of reaction organic substance is precipitated by addition of excess metal ion solution and the excess metal in solution is determined by titrating with EDTA solution.. Alternatively the precipitate of metalorganic complex is decomposed and liberated metal is titrated with EDTA solution. Examples Alkaloids like codeine, strychnine are precipitated as iodobismuthate . Tranquilizer like chlorpromazine forms cadmium iodide complex; purine, barbiturates forms derivatives with zinc and mercury.

12. 4. METAL ION INDICATORS A number of metal ion indicators are used in complexometric titrations. Metal ion indicator can itself act as chelating agent. But their metal complexes have different colour from the reagents themselves. They are called metallochromic indicators. Based on the concentration of metal ions, these indicators change their colour which indicate the end point of the titration. These are also called pM indicators pM is the negative logarithm of metal ion concentration and can be represented as: pM = log [M] The value of pM can be derived from stability constant equation as follows: K = [MX]/[M][X] Then , [M] = [MV[X] K Take log on both sides, then log [M] = log ([MX)/[X]) - log K pM = log ([X)/[MX]) – pK

13. When [X] = [MX] which means that there is equal activity of metal ion and complex, So pM = - pK or pM = pK ’ where K' = -K The choice of indicator depends upon its stability. The indicator should be half complexed and half free at pM value. So pM value can also be defined as value when 50% of the metallochromic indicator is complexed and 50% is in free form.

14. EXAMPLES OF INDICATORS AS PER IP CALCON It is sodium 2-hydroxyl (2- hydroxyl-1-napthylazo) naphthalene- 4 – sulphate . It gives purple red colour with calcium ionin alkaline solution. In absence of metal ions (when EDTA is in excess) that gives blue colour . It is employed as calcon mixture which one part calcon and 99 parts of sodium chloride.

15. CATECHOL VIOLET It forms highly coloured complex with wide range of metals. Complex with metals are blue in colour in acidic solution. Thorium (Th4+) complex at pH 3, Bismuth at pH 1.5 are stable. Other metals like Magnesium, Manganese, Cobalt, Zinc, Calcium, Cadmium can be titrated in pH range of 4-7. 0.1 % solution in water is employed as an indicator.

16. ERIOCHROME BLACK T (MORDANT BLANK-II) Chemically it is sodium 1-( 1- hydroxyl-2-naphthylazo) – 5- nitro-2- naphthol-4- sulphonate ). 0.2 gm of dye with 2 gm of hydroxylamine hydrochloride in 50 ml methylamine hydrochloride is 50 ml methyl- alchohol is employed in titration. A mixture of 0.2 % Mordnet black II with 100 parts of sodium chloride is also employed as indicator. It has, blue colour at pH 10 and complex has red color at pH pH 10. Below 6.3 and above pH 11.5 dye has reddish colour . Use buffer of pH 10 is essential. Metals like Magnesium, Calcium, Cadmium, Zinc, etc., gives excellent results when directly titrated. For Barium and Strontium black titration with titration with Magnesium metal solution is adopted.

17. MUREXIDE (AMMONIUM PURPURATE) A mixture of 0.2 % dispersed in sodium chloride is ued for determination of Calcium at pH 12.0. Complex of calcium Murexide gives blue violet color while indicator solution has red violet colour . This indicator gives better result when 0.5 naphthol green is incorporated in it. Calcium can be estimated in presence of magnesim .

18. 5. MASKING AND DEMASKING AGENTS One of the important aspect of complexometric titration is its, adoptability in estimation of two or more metals in the same solution. This can be done either by selection of suitable pH at which one metal a forms complex without the involvement of other metal ion or by using a suitable masking agent. A masking agent is called as auxiliary chelating agent or complexing agent. It is a substance that will form complex more strongly with the metal than the titrant under the conditions of titration. Some examples of masking agents and the metals they react are with triethanolamine for aluminium and iron; thioglycerol for copper; potassium cyanide for heavy metals; ammonium fluoride for iron and aluminium etc. Masking is an equilibrium process and it is possible to reverse it by using demasking agents.

19. Name of Masking Agents Metals that can be masked Triehanolamine Aluminium,Iron Thioglycerol Copper Pottassium Cyanide and Sodium Cyanide Heavy Metals Ammonium Fluoride Iron, Alumium EXAMPLES OF MASKING AGENTS

20. Demasking Agent It is a substance which releases masked metal ion. Formaldehyde or chloral hydrate can release the masked zinc ion by potassium cyanide. Such agents are useful in determination of specific metal ion from their mixture with other ions. Examples of Demasking Agent:- Formaldehyde-acetic acid solution is a demasking agent that is used complexes of zinc and cadmium. [Zn(CN)41- + 4H+ 4HCHO-> Zn++ 4HO.CH2-CN

21. Addition of precipitants:- Precipitating agents can be used to precipitate some of the interfering ions. These ions are precipitated and then separated and estimated individually. For example: oxalate used in the precipitation of interfering ions such as lead or calcium, ferrocyanide used in the precipitation of interfering ions zinc and copper. Addition of complexing agents:- Some complexing agents form complexes with the interfering ions which are more stable complexes than EDTA complexes. So these ions do not interfere in the titration of main ion. For example:- Ascorbic acid and ferrocyanide used as complexing agent to complex ferric ion , Triethanolamine complexing agent used to complex Aluminium and iron .etc. 3 pH control: pH changes can be used to eliminate interference in the titration by any impurity. For example: EDTA complexes are unstable below pH 7 but Tin (Sn4+), Iron (Fe3+), Cobalt (Co3+) and Thorium (Th4+) complexes are stable between pH 3 to 7.

22. 6. STANDARDISATION OF DISODIUM EDTA 0.05 M (sodium edetate ) is prepared and standardized as follows Dissolve 18.6 g of disodium EDTA in sufficient water to produce 1000 ml. Weigh accurately about 0.8 g of granulated zinc, dissolve by gentle warming in 12 ml of dil. hydrochloric acid, add five drops of bromine water. Boil to remove excess bromine, cool, and add sufficient water to produce 200.0 ml. Pipette 20 ml of the resulting solution into a flask and nearly neutralize with 2N sodium hydroxide. Dilute to about 150 ml with water, add sufficient ammonia buffer of pH 10 to dissolve precipitate and add 5 ml in excess. Add 50 mg of mordant black II mixture and titrate with the e disodium EDTA solution until the solution turns green. Each 0.003269 g of granulated zinc is equivalent to 1 ml of 0.05 M disodium EDTA. Zn 2+ + [H 2 Y] --> [ ZnY ] 2 + 2H +

23. 7. ESTIMATION OF MAGNESIUM SULPHATE PRINCIPLE: Magnesium sulphate is titrated directly against disodium edetate in the presence of strong ammonia-ammonium chloride solution. End point is detected by mordant black II mixture as an indicator. Reaction involved in this titration is as follows. Mg 2+ + EDTA --> Mg-EDTA + 2H + PROCEDURE: Weigh accurately about 0.3 gm of magnesium sulphate in a conical flask and dissolve in 50 ml of distilled water. Add 10 ml of strong ammonia-ammonium chloride solution. Add 2 drops of mordant black II mixture as an indicator. Then fill the burette with standardized disodium edetate solution. Start titration with the disodium edetate until reach the endpoint.

24. The approach of the endpoint is suggested by the change of pink colour to blue. Record the reading of burette. Repeat the titration three times to get precise readings. Take mean of them and calculate the percentage purity of magnesium sulphate . Equivalent factor of magnesium sulphate for 1 ml of 0.05 M disodium edetate is 0.00602.

25. 8. ESTIMATION OF CALCIUM GLUCONATE PRINCIPLE: This is a replacement titration. Magnesium forms complex with mordant black II mixture indicator which shows first colour . Mg 2+ + In- --> Mg-In Magnesium In Indicator Magnesium- Indicator ion complex (coloured1) Magnesium-indicator complex is much more stable than calcium-indicator complex therefore calcium has not any effect on magnesium-indicator complex. On titration against disodium edetate complex of calcium and disodium edetate is formed. Ca 2+ + EDTA --> Ca - EDTA Calcium Disodium edetate Calcium - disodium ion edetate complex

26. When calcium is totally consumed, next drop of disodium edetate breaks the Magnesium - Indicator complex and make complex with magnesium by liberating free indicator. End point is detected by observing second colour at that time. Mg - In + EDTA --> Mg-EDTA + In - Magnesium- Magnesium Free indicator Indicator – disodium complex ( coloured 2) complex ( coloured 1)

27. PROCEDURE:- Weigh accurately about 0.5 g of calcium gluconate in a conical flask and dissolve in 50 ml of warm water. Allow to cool. Add 5 ml of 0.05 M magnesium sulphate . Add 10 ml of strong ammonia-ammonium chloride solution. Add 2 drops of mordant black II mixture as an indicator. Then fill the burette with standardized disodium edetate solution. Start titration with the disodium edetate until reach the endpoint. Record the reading of burette. Repeat the titration three times to get precise readings. Take mean of them and calculate the percentage purity of calcium gluconate. Repeat the titration again using same procedure without calcium gluconate for blank reading. Equivalent factor of calcium gluconate for 1 ml of 0.05 M disodium edetate is 0.02242.

28. T H A N K Y O U