Non-Aqueous Titrations PDF

Non Aqueous Titrations What Are Non Aqueous Titrations? Titrations that are done in a medium completely free from water (using non aqueous solvents). Reasons : 1. Solubility :Substances which aren’t soluble in water but soluble in non aqueous solvent 2. Very weak acids or bases: that cannot be det...

Non Aqueous Titrations What Are Non Aqueous Titrations? Titrations that are done in a medium completely free from water (using non aqueous solvents). Reasons : 1. Solubility :Substances which aren’t soluble in water but soluble in non aqueous solvent 2. Very weak acids or bases: that cannot be determined accurately in aqueous solution. (no sharp end points) Aim : 1. Increase the dissociation of weak acids and weak bases to behave like strong acids & strong bases. 2. This is achieved by using non aqueous solvents instead of water. 3. To understand the increase in dissociation constant we must study the concept of acids and bases suggested by Bronsted Advantages : 1. Many Pharmacopeial methods for drugs determination are non aqueous titrations 2. Insoluble substances in water (organic acids and bases) but soluble in non aqueous solvent 3. Very weak acids or bases that cannot be determined accurately in aqueous solution 4. Stepwise determination of mixture of weak acids or weak bases with near dissociation constants Disadvantages : 1. expensive 2. volatile 3. toxic Acid base theory The conjugate base is the ion remaining after the acid has lost a proton The conjugate acid is the species created when the base accepts the proton Arrhenius theory has many objections (Pionts of weakness): 1. Aqueous solutions of ammonia & amines are basic although they don't contain OH- 2. Solutions of Na metal in water is basic due to formation of NaOH which gives OH-, but it was found that solution of Na metal in ethano (C2H5O-) is more basic than water 3. It doesn’t discuss the role of the solvent; HCI gas has no acidic properties on dry litmus paper, only behaves as an acid when moisten HCI in benzene doesn’t act as an acid because benzene not accepting protons from HCI  Role of solvents in non-aqueous titration Leveling effect: ability of solvent to increase strength of weak acids/bases to become strong acids /base à direct titration Differentiating effect: The ability of the solvent to differentiate between the strength of acids or bases. Differentiating effect of solvent is useful in stepwise titration of acidic mixture Methyl isobutyl ketone and acetic acid has differentiating effect on acids HClO4 , H2SO4 , HCl , HNO3 Relative acidity and alkalinity According To Bronsted theory, acidity and alkalinity of substance is relative to solvent. If the substance is more acidic than solvent, it will behave as an acid & vise versa. The substance behaves as an acid if the solvent is relatively more basic and it behave as a base if the solvent is more acidic.  Solvent Properties that affect levelling & differentiating effect IMPORTANT NOTES It causes the sample to be ionized without any interference from the solvent The higher the D à the higher Ks As Autoprotolysis α DEC Except water: 1. Has high DEC and low autoprotolysis 2. Water is unique: low Ks + highest D..... which allows completeness of reaction. The substance must be soluble in the chosen solvent. All points should be considered together. Formic acid...high D....high autoprotolysis Acetic acid....low D.....low autoprotolysis... (more preferable) Standardization of titrants 1. Standardization of acetous HCIO,: is done against potassium acid phthalate in glacial acetic. 2. Standardization of NaOCH3 or Tertiary butyl ammonium hydroxide is done against benzoic acid.  Basic Sample (ACIDIMETRY ) Sample Solvent Titrant Indicator Loratadine Glacial acetic acid = Dissolve Sample + HClO4 in glacial Crystal violet in glacial acetic Antihistaminic drug Levelling Effect acetic acid à acid weak base + water insol Strong Acid Titrant violet to bluish green Amino acids Glacial acetic acid HClO4 in glacial Crystal violet in glacial acetic basic group (NH2) 1. Leveling effect acetic acid à acid 2. Suppression of COOH Strong Acid Titrant violet to bluish green Methyldopa Glacial acetic acid HClO4 in glacial Crystal violet in glacial acetic Aromatic amino acid + slightly 1. Leveling effect on weak basic NH2 group acetic acid à acid soluble in water 2. Suppression of carboxylic group Strong Acid Titrant violet to bluish green 3. Dissolving methyldopa Mixture of 1ry, 2ry & 3ry amines (1) Total amines: (normal solvent-titrant – indicator) (2) Tertiary amine (R3N) only: ON NEW SAMPLE reflux with acetic anhydride to acetylate 1ry and 2ry - 3ry amine is determined by titration with standard acetous HClO4 & acetous crystal violet as in step 1 à Ep2 - Ep1- Ep2 = Total – 3ry = 1ry +2ry (3) Secondary & Tertiary amines (R2NH) & (R3N): Heating with salicylaldehyde salicylaldehyde reacts with 1ry amine only - Titrant: Titrate 2ry and 3ry amines with HCl in isopropanol à EP3 E1= Total 1ry = E1 - E3 = Total – (2ry + 3ry) E2= 3ry 2ry = E3 - E2 = (2ry + 3ry) - 3ry E3= 2ry + 3ry 3ry=E2 Acidic Sample (ALKALIMETRY) Sample Solvent Titrant Indicator Allopurinol Ethylene diamine Sodium methoxide Thymol blue Weak acid + insoluble (NaOCH3) yellow to blue Barbiturates Ethylene diamine Sodium methoxide Thymol blue Weak acids + water insoluble (NaOCH3) yellow to blue Sulphonamides Ethylene diamine Sodium methoxide Thymol blue W.acid + low water solubility 1. Leveling effect on weak acidic group (NaOCH3) yellow to blue 2. Suppression of NH2 group Mixture of mineral & carboxylic acids Solvent: Methyl isobutyl ketone à differentiating effect on acids Titrant: Tertiary butyl ammonium hydroxide. Endpoint detection: Potentiometry