Diazotization titrations

Diaozotization titrations

1. Diazotization titrations or Sodium Nitrite Titrations R DEEPTHI Assoc. Professor Vignan institute of pharmaceutical technology, V isakhapatnam

2. Diazotization Titrations INTRODUCTION The diazotization titration is nothing but the conversion of the primary aromatic amine to a diazonium compound. This process was first discovered in 1853 and was applied to the synthetic dye industry . The reaction mechanism was first proposed by Peter Griessin . In this method, the primary aromatic amine is reacted with the sodium nitrite in acidic medium to form a diazonium salt. This method is first used in the determination of dyes.

3. PRINCIPLE The principle involved in this method is that the primary aromatic amine present in the sample reacts with the sodium nitrite in the presence of acid such as hydrochloric acid to obtain a diazonium salt. R − NH 2 + NaNO 2 + HCl R − N + ≡ N − Cl − + NaCl + H 2 O Sodium nitrite is added to the solution of amine in the presence of acid at 0–5 °C. The amine reacts with the nitrous acid to form nitrosamine, which is followed by the tautomerisation and the water molecule is lost to form the diazonium ion. This diazonium ion is stabilized by the displacement of the positive charge at the ortho and para positions of the ring. C 6 H 5 NH 2 + NaNO 2 + HCl C 6 H 5 N = NCl + NaCl + H 2 O

4. THEORY When sodium nitrite is reacted with the hydrochloric acid sodium chloride and nitrous acid are formed. NaNO 2 + HCl NaCl + HNO 2 The obtained nitrous acid is reacted with the primary aromatic amine to form the diazonium salt. The excess of nitrous acid is removed by the addition of ammonium sulphamate solution. R − NH 2 + HNO 2 R − N = NH + H 2 O The end point is detected by the formation of the blue colour with starch iodide paper. This is prepared by immersing the filter paper in the starch mucilage and potassium iodide solution. KI + HCl KCl + HI 2HI + 2HNO 2 I 2 + 2NO + 2H 2 O I 2 + starch mucilage blue colour end point

5. PROCEDURE The general procedure is followed by weighing the sample(2.5g) and transferring it into the standard flask (250ml). Then add 50mlof concentrated hydrochloric acid and (5g) potassium bromide are added and the rest of the volume is filled with the distilled water. This resulting solution is known as the standard solution. The appropriate volume of the standard solution is pipetted out and the temperature is maintained at 0-5 °C. Then the solution is titrated with the 0.1N sodium nitrite solution until the starch iodide paper turns into blue colour . Another procedure is —After maintaining the conical flask temperature, the pair of platinum electrodes is immersed. Then the electrodes are connected to the potentiometer and slowly titrated with sodium nitrite solution until a permanent deflection is observed at the end point.

6. END POINT DETECTION The end point in diazotization titration is detected by the following procedures: The excess of nitrous acid is determined by the addition of the starch iodide as an external indicator. After diazotization, one drop of the resulting solution is placed on the starch iodide paper which changes into dark colour . Another method for the detection of end point is Electrochemical method: B y immersing the platinum electrodes in the resulting solution and it is also detected by the dead-stop end point method . 0.5g Sample + 10ml HCl + 75ml Water NaNo 2

7. The next method for the detection of the end point in the diazotization titration is by adding the potassium iodide to the nitrous acid with excess acid which liberates the iodine. The liberated iodine is back titrated with the sodium thiosulphate using starch as the external indicator. The end point is detected by appearance of blue colour . KI + HCl HI + KCl HI + 2HNO 2 I 2 + 2NO + 2H 2 O Preparation and Standardization of the Sodium Nitrite Solution Appropriately weighed sodium nitrite is dissolved in the water and made up to the desired volume. Standardization of the sodium nitrite is carried out by titrating the previously dried sulphanilamide dissolved in the water and hydrochloric acid solution which is cooled to 15 °C with standard solution of the sodium nitrite.

8. Preparation and Standardization of 0.1N Sodium Nitrite solution

9. FACTORS AFFECTING THE DIAZOTIZATION Acid concentration. pH of the NaNO 2 . Temperature of the reaction (should be maintained at 0–5 °C): the diazonium compounds are decomposed at elevated temperatures. Reaction time (it takes 10–15 min): the compounds react with nitrous acid at different rates based on the nature of the compound. Slow diazotizable groups: sulpha groups, carboxylic groups and nitrogen oxide group. Fast diazotizing groups: anilide , toluidine and aminophenol.

10. CONDITIONS FOR THE DIAZOTIZATION TITRATION The following conditions are required for the diazotization titration of the amino group containing samples. They are as follows: Rate of titration: Addition of sodium nitrite to the sample solution takes time to react with the amino group present in the sample solution. Different amino compounds react with the nitrous acid at different rates. Based on this, the amino compounds are classified into two main groups. They are as follows: Slow diazotizable compounds Example : Sulphanilic acid and anthranilic acid Fast diazotizable compounds Example : Aniline, aminophenol, and toluidine The reaction rate is increased by the addition of the potassium bromide solution. Temperature: Maintenance of the temperature is the main condition for the diazotization titration. The diazonium salts formed are not stable at elevated temperatures. They are readily decomposable at elevated temperatures, therefore, the temperature should be maintained at 0–5 °C.

11. Types of Diazotization Titrations There are mainly three types of methods based on the titration procedure. They are as follows : Direct method: The main principle involved in this method is to treat the amino group containing drug with the acid solution . The resulting solution is immersed in the cold water bath or ice water bath by maintaining the temperature at 0–5 °C. Then this solution is titrated with the sodium nitrite solution. The end point is determined by the above-mentioned methods. Indirect method: The principle involved in this method is that the excess nitrous acid is added to the titration sample solution and it is back titrated with the other appropriate titrant. This method is mainly used for the titration of insoluble diazonium salts.

12. Other method ( Diazo oxide formation method): The main principle involved in this method is the formation of the diazo oxide which is more stable than the diazo compounds. For example, the aminophenol is readily oxidized by the nitrous acid and converted to the quinones in the presence of copper sulphate solution and forms the diazo oxide compounds. This readily undergoes the coupling reaction with the nitrous acid.

13. ADVANTAGES Selective for the all types of sulphonamides . Sensitive Reproducibility DISADVANTAGES Applicable for a very less variety of samples. Relatively slow when compared to other methods. Temperature conditions to be properly maintained throughout the reaction. The end point detection is very difficult. The colour produced is not stable. Lack of specificity.

14. APPLICATIONS Used in the determination of the sulphonamides . Method: An accurately weighed 1 mg sample of sulphonamide is dissolved in the 4 ml of concentrated HCl and in 10 ml of distilled water. Then , this solution is cooled to 15 °C and titrated with the 0.1 M of sodium nitrite solution. The end point is determined by streaking one drop of the titration solution on the starch iodide paper until blue colour is appeared . The percentage amount of the sulpha drug is determined by the following equation :

15. where V is the volume of the titrant consumed; M is the molarity of the titrant; EW is the equivalent weight of the drug; W is the weight of the sample. Used in the determination of the chlorpheneramine . Method: The accurately weighed sample is added to the 5 ml of HCl and 50 ml of distilled water. Then the solution is cooled to 15 °C. Then the solution is slowly titrated with the 0.1 N sodium nitrite solution using starch iodide paper as the indicator. Used in the determination of the dopamine, dapsone Used in the determination of the procaine, benzocaine Used in the determination of the amphetamine. Used in the determination of the procaine Used in the determination of the ephedrine . All sulpha drugs ex: sulphadoxime , sulphacetamide , sodium amino salicylate

16. Used in the determination of the P -amino benzoic acid ( vitamin B 4 ). Method: The accurately weighed sample is added to the 5 ml of HCl and 50 ml of distilled water. Then the solution is cooled to 15 °C. Then the solution is slowly titrated with the 0.1 N sodium nitrite solution using starch iodide paper as the indicator. 1 ml of 0.1 N sodium nitrite ≡ 0.01371 g of vitamin B 4

17. REVIEW QUESTIONS What is the principle involved in the diazotization titrimetry ? What are the conditions required for the diazotization titrimetry ? What are the example drugs assayed by the diazotization titrimetry ? What are the advantages of diazotization titrimetry ? What are the factors that affect the diazotization end point? What are the different methods used for the end point detection in the diazotization titrimetry ?

18. Conductometry INTRODUCTION Conductometry is the measurement of the electrical conductivity of a solution. The conductance is defined as the current flow through the conductor. In other words, it is defined as the reciprocal of the resistance . The unit for the conductance is Seimens (S) which is the reciprocal of Ohm's (Ω −1 ). This method is mainly used for the determination of the physico -chemical properties of the compounds.

19. PRINCIPLE The main principle involved in this method is that the movement of the ions creates the electrical conductivity. The movement of the ions is mainly depended on the concentration of the ions. A + B − + C + D − AD + C + B − where A + B − is the solution of strong electrolyte; C + D − is the solution of the reagent. Here the ionic concentration of A + is determined by reacting the electrolyte solution with the reagent solution so that the A + ions are replaced by the C + ions. This replacement of the ions with the other ions shows the conductance increase or decrease. This is done mainly by the replacement of the hydrogen ion with other cation .

20. THEORY The theory is mainly based on Ohm's law which states that the current ( I ) is directly proportional to the electromotive force ( E ) and inversely proportional to the resistance ( R ) of the conductor: I = E/R The conductance is defined as the reciprocal of the resistance. The resistance is expressed by the following equation: R = ρ l /a where ρ is the resistivity; l is the length; a is the cross-sectional area of the homogenous material. Therefore, C = 1/ R  = k / la where K is the conductivity; l is the length; a is the cross-sectional area of the homogenous material.

21. Then the molar conductivity is defined as the conductivity due to 1 mole and it is expressed by the following formula: Λ = 1,000 k/C where K is the conductivity; C is the concentration of the solution in mol /l. The sample solution is placed on the cell which is composed of platinum electrodes. These are calibrated with the help of known conductivity of the solution, for example, standard potassium chloride solution. Cell constant is defined as the conductivity of the cell: R = ρ l /a where ρ is the resistivity; l is the length; a is the cross-sectional area of the homogenous material. Cell constant = specific conductivity/observed conductivity Then the cell constant is determined by the substitution of the value of the specific conductivity of N/50 KCl solution at 25 °C. The value is 0.002765 mhos which is given by the Kohlrausch . Cell constant = 0.002765/observed conductivity

22. Methods for the Conductance Measurements The conductance of the sample solution is measured by the resistance measurement by the Wheatstone bridge. The following are the different bridges used for the measurement of the conductance: Kohlrausch bridge: It consists of a meter bridge wire AB with a fixed resistance R on both the ends. To increase the length of the wire, it is connected to the resistance box R*, conductance cell C and the head phone D and a small induction coil I. All these are operated by the battery. Headphone is used for the detection of the conductance difference.

23. Conductivity cell: These conductivity cells are made up of glass. These are commonly employed by dipping in the analyte solution. It is composed of pair of electrodes placed at a constant distance. There are mainly three types of cells used as conductivity cells: Type A: This consists of the electrodes placed at a large distance and is used for the measurement of the high conductance.

24. Type B: In this type, the cell is dipped in the sample solution to measure the conductance in the titrations .

25. Type C: In this type, large electrodes are placed with small distance. This type cell is mainly used for the measurement of the low conductance. They are made up of glass fitted with the platinum electrodes .

26. APPARATUS The conductometric apparatus is composed of the following. The electrodes are made up of platinum sheets. These electrodes are fixed in a constant distance and are sealed in the connected tubes. To avoid the polarisation effect, these electrodes are coated with the platinum black. This is done by the 2–3% of the chloroplatinic acid solution. Then 0.02–0.03 g of lead acetate solution is taken into the cell. On passing the current, chloroplatinic acid under goes electrolysis and the electrodes are blackened. Then these electrodes are repeatedly washed with the distilled water and finally with the conductivity water. The conductivity water is the water obtained by treating the distilled water with small amount of sodium hydroxide and potassium permanganate. Here the induction coil is used for inducing current.

27. METHOD The sample solution is placed in the conductivity cell at constant temperature. The temperature is maintained constant with the help of the thermostat. Then the cell is connected to the resistor box R and the alternating current is passed through the cell with the help of induction coil. Then the conductivity of the solution is measured by the following equation: Conductivity of the solution = 1/resistance of the solution

28. FACTORS AFFECTING THE CONDUCTIVITY MEASUREMENTS Temperature: The conductivity of the electrolyte increases with the temperature increase. This is because of the ions mobility by increasing the temperature . Concentration of the sample solution: The concentration of the solution is inversely proportional to the conductivity of the sample solution. The conductance is decreased with the increase in the concentration. Hence diluted solutions are used for the conductivity measurements . Number ions present in the sample solution: This is mainly based on the dissociation of the compounds into ions. That is mainly of the number of ions present in the solution. The number of ions present in the solution is directly proportional to the conductance. Strong electrolytes completely dissociate into ions and have high conductance . Charge of the ions: Negative charge of the ions increases the conductivity where as the positively charged ions decreases the conductivity . Size of the ions: The conductivity is inversely proportional to the size of the ions. That is the increase in the size of the ions increases the conductivity.

29. Types of the Conductometric Titrations Acid–base titrations: In this method, the conductance of the hydrogen ions and hydroxyl ions are compared with the conductivity of the sample solution. Strong acid with a strong base: For example, take the titration of the HCl with NaOH . [ H + Cl − ] + [ Na + OH − ] [ Na + Cl − ] + H 2 O The initial conductivity of the HCl solution is high because of the protons from the dissociation of the acid. Then titrating with NaOH dissociates into Na + and OH − . This hydroxyl ion reacts with the H + ions to form the water. This shows the decrease in the conductivity. After completion of the reaction, the excess addition of the NaOH shows the increase in the conductivity. The plot between the conductivity and the volume of the titrant shows the V-shaped curve.

30. Strong acid with weak base: For example, titrations of the strong acid such as HCL with the weak base such as the ammonium hydroxide. HCl + NH 4 OH NH 4 Cl + H 2 O Same as the titration of the strong acid with strong base, it initially shows the increase in the conductivity because of the H + ions. This conductivity is decreased by the addition of the weak base that is with the NH 4 OH that neutralises the H + ions with the OH − ions and decreases the conductivity. The excess addition of the NH 4 OH does not show the change in the conductivity. Then the plot between the conductivity and the volume of the titrant shows the plateau.

31. Weak acid with a strong base: The weak acid such as acetic acid is titrated with the strong base such as sodium hydroxide. CH 3 COOH + NaOH CH 3 COONa + H 2 O The acetic acid dissociates to produce the H + ions which shows the high conductivity and is titrated with the sodium hydroxide which is dissociated to produce the OH − ions which shows slight increase in the conductivity by the formation of the CH 3 COONa at the equivalence point. Then it shows the gradual increase in the conductivity by the addition of excess titrant. Then plot the graph between the conductivity and the volume of the titrant which shows the plateau.

32. Weak acid with weak base: The weak acid such as the acetic acid is titrated with the weak base such as ammonium hydroxide. CH 3 COOH + NH 4 OH CH 3 COONH 4 + H 2 O The acetic acid is dissociated and it combines with the ammonium ion after dissociation of the ammonium hydroxide. This forms the ammonium acetate salt which shows the increase in the conductivity. After attaining the equivalence point, the addition of the titrant does not shows the conductivity change. The plot between the conductivity and the volume of the titrant shows the plateau.

33. Precipitation titrations: When compared to the acid–base titrations, precipitate titrations are not that much accurate because of the more number of the interferences. These are also known as the replacement titrations. The precipitate formation is taken as the end point when the conductivity is measured. Example: Potassium chloride is titrated with the precipitating agent such as the silver nitrate solution. KCl + AgNO 3 AgCl + KNO 3

34. Initially the addition of the silver nitrate to the potassium chloride shows the stability in the conductivity and the excess of the silver nitrate addition increases the conductivity because of the formation of the single precipitate.

35. In another case, the titration will form two precipitates. For example, magnesium sulphate is titrated with the barium hydroxide and forms two precipitates: the magnesium hydroxide and the barium sulphate . Initially the plot shows the decrease in the conductivity and then shows the increase in the conductivity. MgSO 4 + Ba(OH) 2 Mg(OH) 2 + BaSO 4

36. Redox titrations: In this method, the decrease in the hydrogen ions concentration shows the decrease in the conductivity at the end point. Example: The titration of the ferrous ions with the dichromate ions. 6Fe +2 + Cr 2 O 7 + 14H + 6Fe +3 + 2Cr +3 + 7H 2 O The hydrogen ions show sharp decrease in the conductivity. After the equivalence point, the addition of the excess of the titrant shows the stability in the conductivity.

37. ADVANTAGES Appropriate for the dilute solutions. Broad selectivity. End point is determined by plotting the graph. No need for the specific conductivity. No need of indicator . DISADVANTAGES Less accurate when compared to other methods: Because the high concentrations are not measured by the conductometric titrations. The solutions are compulsory diluted for the measurements. Less satisfactory when compared to other methods.

38. APPLICATIONS Used in the determination of the basicity of the acids. The basicity is defined as the number of carboxylic acid groups attached to the molecules. Used in the determination of the sparingly soluble salts such as barium sulphate and lead sulphate . Used in the determination of the purity of the water. Used in the determination of the salinity of the sea water. Used in the determination of the ionic product of the water. Used in the quantitative analysis of the compounds.

39. REVIEW QUESTIONS What is the principle involved in the conductometry ? What is the theory of conductometry ? Explain the concept of molar conductivity. Explain the concept of cell constant. What are the different methods of conductivity measurements? What are the factors affecting the conductivity measurements? What are the different types of conductometric titrations? What are the different types of applications of conductometry ?