1. Neutralization Titration (Acid/base titration) Dr. Mohammad Khanfar

2. Acid/Base Titration Standard Solutions The standard solutions used in neutralization titrations are strong acids or strong bases because these substances react more completely with an analyte than do their weaker counterparts, and they therefore provide sharper end points. HCI, HCIO 4, H 2 S0 4, NaOH, and KOH.

3. Acid/Base Titration Acid/Base Indicators Many substances, both naturally occurring and synthetic, display colors that depend on the pH of the solutions in which they are dissolved. An acid/base indicator is a weak organic acid or a weak organic base whose undissociated form differs in color from its conjugate base or its conjugate acid form. Indicator pH range = pKa ± 1 Indicator should fall within the range of inflection of the strong acid/strong base titration curve.

4. Acid/Base Titration Internal structural changes accompany dissociation and cause the color change

5. Acid/Base Titration Methyl orange, pKa 3.7

7. Titration Of Strong Acids And Strong Bases Consider the titration of 50 ml of 0.05 M HCl (analyte) with 0.1M NaOH (titrant). First we determine equivalent point M1V1 = M2V2 V = 25ml Initial Point Before any base is added, the solution is 0.0500 M in H 3 0 +, and pH = -log[H 3 0 + ] = -log 0.0500 = 1.30 After Addition of 10.00 mL of Reagent The H + ion concentration is decreased as a result of both reaction with the base and dilution. pH = 1.6

8. Titration Of Strong Acids And Strong Bases After Addition of 25.00 mL of Reagent (The Equivalence Point) At the equivalence point, neither HCl nor NaOH is in excess, and so the concentrations of hydronium and hydroxide ions must be equal pH = 7 After Addition of 25.10 mL of Reagent The solution now contains an excess of NaOH, pH = 10.12

9. Titration Of Strong Acids And Strong Bases The Effect of Concentration

10. Titration Of Strong Acids And Strong Bases Titration curves for HCI with NaOH. Curve A: 50.00 mL of 0.0500 M HCI with 0.1000 M NaOH. Curve B: 50.00 mL of 0.000500 M HCI with 0.001000 M NaOH. The Effect of Concentration

11. Titrating a Strong Base with a Strong Acid Titration curves for strong bases are derived in an analogous way to those for strong acids. Short of the equivalence point, the solution is highly basic, the hydroxide ion concentration being numerically related to the analytical molarity of the base. The solution is neutral at the equivalence point and becomes acidic in the region beyond the equivalence point then the hydronium ion concentration is equal to the analytical concentration of the excess strong acid.

12. Titrating a Strong Base with a Strong Acid Titration curves for NaOH with HCl. Curve A: 50.00 mL of O.0500 M NaOH with 0.1000 M HCl. Curve B: 50.00 mL of 0.00500 M NaOH with 0.0100 M HCl.

13. Strong Acid/Strong Base Titration There are only a few direct strong acid/strong base titrations carried out in pharmacopeial assays: perchloric acid, hydrochloric acid, sulphuric acid, and thiamine hydrochloride One major application of strong acid/strong base titration is determination of aldeyde and ketons in essentail oil. The determination of aldehydes depends upon the reaction with hydroxylamine hydrochloride: The liberated hydrochloric acid can be titrated with standard alkali.

14. Strong Acid/Strong Base Titration Example. Determination of the %w/w of cinnamic aldehyde in cinnamon oil. 100 g of cinnamon oil was reacted with adequate excess of hydroxylamine hydrochoride (15 ml). The reaction mixture was titrated with 160ml of 0.5M KOH until the red color of methyl orange changes to full yellow. Calculate the %w/w of cinnamic aldehyde (132.16 g/mol).

15. Strong Acid/Strong Base Titration Calcium hydroxide (Ca(OH) 2 )solution Although this is a fairly strong alkaly and is titrated with HCl solution, methyl orange is not used as indicator. The solution absorbs carbon dioxide from the atmosphere to form carbonate (pKa 7.7) but since the free Ca(OH) 2 and not the total alkali content is required, phenolphthaline is used as indicator.

16. Weak acid/strong base and weak base/strong acid On addition of a small volume of the strong acid or strong base to a solution of the weak base or weak acid, the pH rises or falls rapidly to about 1 pH unit below or above the pKa value of the acid or base. Often a water-miscible organic solvent such as ethanol is used to dissolve the analyte prior to addition of the aqueous titrant. Example. Titration of 50.0 ml of 0.1 M acetic acid (pKa 4.76) with 0.1 M NaOH. Initial pH: calculated from [H + ] = (ka. c) 1/2 pH before equivalence point: A state of equilibrium between the acid and its conjugate base formed, and the pH is calculated from Henderson–Hasselbalch equation

17. Weak acid/strong base and weak base/strong acid At equivalence point: all acetic acid is consumed and converted to sodium acetate, and pH is calculated starting from [OH - ] = (Kb. c) 1/2 pH after equivalence point: After the addition of excess amount of NaOH, both the excess base and the acetate ion are sources of hydroxide ion. The contribution from the acetate ion is small, however, because the excess of strong base represses the reaction of acetate with water. pH = 14 – pOH

18. Weak acid/strong base and weak base/strong acid Curve for the titration of acetic acid with sodium hydroxide. Curve A: 0.10 M acid with 0.1000 M base. Curve B: 0.0010 M acid with 0.0010 M base.

19. Weak acid/strong base and weak base/strong acid Titration curve of 25 ml of 0.1M solution of aspirin (pKa 3.5) titrated with 0.1M NaOH

20. Weak acid/strong base and weak base/strong acid Titration curve of 25 ml of 0.1M solution of quinine(pKa 8.05) titrated with 0.1M HCl

21. Weak acid/strong base and weak base/strong acid For an acid, the measured pH when the acid is exactly half neutralized is numerically equal to pKa. For a weak base, the pH at half titration must be converted to pOH, which is then equal to pKb. Weak acid with strong base, end point will be basic then phenolphthalein can be used in general Weak base with strong acid, end point is acidic so methyl orange can be used in general.

22. The effect of acid strength (dissociation constant) on titration curve. Each curve represents the titration of 50.00 mL of 0.1000 M acid with 0.1000 M base. The pH change in the equivalence-point region becomes smaller as the acid becomes weaker, that is, as the reaction between the acid and the base becomes less complete.

24. 5-fluorouracil A: Ureide nitrogen, very weak acidic, pKa 13 B: Ureide nitrogen, weak acid, pKa 7.0

25. Guanithedine A: guanidine moiety, one of the strongest nitrogenous base pKa 11.4 B: Tertiary amine, pKa 8.3 Sulphadiazine A: pyrimidine ring, very weak basic nitrogen, pKa < 2 B: Sulfonamide nitrogen, weak acid, pKa 6.5 C: Weakly basic aromatic amine (aniline) pKa < 2

26. Weak acid/strong base and weak base/strong acid Blank titration In general, blank determinations are used if the volumetric solution is unstable or if it alters in strength during the assay (heating, interaction with glass, of absorption of atmospheric CO 2 ). Titration without analyte.

27. Some applications of neutralization titration Generally, aqueous acid-base titration is used for any acid or base with pk(a or p) less than 6, can give accurate determinations 1)Estimation of alcohols and hydroxyl values by reaction with acetic anhydride (AA) Alcohols can be determined by reaction with excess AA. The excess AA and acetic acid may be back titrated with KOH using PP as an indicator. Hydroxyl value = the number of mg of KOH required to neutralize a blank titration of the reagents – the number of mg KOH required to neutralize excess AA + acetic acid after reaction with 1 g of the test substance

28. Example. 1.648 g sample of castor oil was refluxed with 5 ml of acetic anhydride for 6 h. 44.6 ml of KOH (0.505 M, 56.1 g/mol) was added to neutralize the excess acetic anhydride and acetic acid. 53.5 ml of KOH required to blank-titrate the 5 ml of the reagent (acetic anhydride). Calculate the hydroxyl value. Some applications of neutralization titration

29. 2) Determination of esters. The determination of ester is performed by hydrolysing the substance to an alcohol and an acid using excess of standard ethanolic KOH solution, and then back-titrating the excess alkali using strong acid (HCl). A blank determination is performed.

30. Some applications of neutralization titration 3) Saponification value as an example of back-titration with blank determination. The saponification value for a fixed oil (vegetable oil) is the number of mg of KOH equivalent to 1 g of oil. A high value means rancidity, low value means possible a adulteration with mineral oil. Almost all edible oils have a saponification value between 188 and 196. Saponification value = (b – a) x molarity x 28.05/weight of sample (g) b = burette reading for blank a = burette reading for sample

31. Some applications of neutralization titration 4) Elemental analysis of nitrogen (Kjeldahl determination) The most common method for determining organic nitrogen (protein, synthetic drugs, and protein content in blood product), which is based on a neutralization titration. In the Kjeldahl method, the sample is decomposed in hot concentrated sulfuric acid to convert the bound nitrogen to ammonium ion. The resulting solution is then cooled, diluted, and made basic. The liberated ammonia is distilled, collected in an acidic solution, and determined by a neutralization titration.

32. Some applications of neutralization titration Kjeldahl method

33. Some applications of neutralization titration Kjeldahl method

34. Weak acid/strong base and weak base/strong acid Polyfunctional acids and bases Some acids and bases can donate or accept more than one proton, i.e. 1 mole of analyte is equivalent to mort than one mole of titrant. If the pKa values of any acidic or basic groups differ by more than 4, then the compound will have more than one inflection in its titration curve. pKa 10.32 pKa 6.38

35. Weak acid/strong base and weak base/strong acid Titration of 1 M sodium carbonate with 1M HCl

36. Weak acid/strong base and weak base/strong acid