Non-aqueous Acid-BaseTitrations Muh. Nur Khoiru Wihadi, S.Pd., M.Sc. • The most commonly used procedure is the titration of organic bases with perchloric acid in acetic acid • Water behaves as both a weak acid and weak base. . as it suitable for the titration of weak acids and bases and provides a solvent in which organic compounds are soluble. thus in aqueous environment. it can compete effectively with very weak acids and bases with regard to proton donation and acceptance.Non-aqueous Titrations • Theory • Non-aqueous titrations is the most titrimetric procedure used in pharmacopoeial assays and serves a double purpose. Non-aqueous Titrations . Non-aqueous Titrations • Theory • The effect of this is that the inflection in the titration curves for weak acids and weak bases is small. thus making end-point detection more difficult. because they approach the pH limits in water of 14 and 0 respectively. • A general rule is that bases with pKa < 7 and acids with pKa > 7 cannot determined accurately in aqueous solution • Various organic solvents may be used to replace water since they compete less effectively with the analyte or proton donation and acceptance. . No water to interfere with titration.Non-aqueous Titrations • Advantages of non-aqueous titrations: • 1) Provide suitable solvent • 2) Increase the basicity or acidity of the analyte. which would give sharper inflection region . a solution of perchloric acid in glacial acetic acid.Non-aqueous Titrations • Non-aqueous titration of weak bases • Solvent: neutral or acidic • Acetic acid is the most common solvent for weak base titration because it does not compete effectively with weak bases for protons. . • Only very strong acid (like perchloric acid) will protonate acetic acid: onium ion • As the CH3COOH2+ ion can instantly donate its proton to a base. therefore. behaves as a strongly acidic solution. • Standarized with KHP . measured but not in excess amount (why?). • The choice of the titrant here is more crucial than in the case of aqueous titration (How?) • Acetic anhydride. is used to remove water from aqueous perchloric acid (the commercially available form). aprotic solvents are added to ionizing solvents to depress solvolysis of the neutralization product and so sharpen the end point • Butanol can be added to enhance the solubility of insoluble substances. • Titrant: most commonly used titrant is perchloric acid.Non-aqueous Titrations • Benzene and chloroform (aprotic solvent) can also be used as neutral solvents • Since dissociation is not an essential preliminary to neutralization. when the base in the form of a salt of a weak acid (tartrate.Non-aqueous Titrations • • • • Indicators: Crystal violet (most common one) 3-quinaldine 4-naphthalein • When a base is in the form of a chloride or bromide salt. 2RNH3+Cl. acetate. or succinate) removal of an anionic counter ion prior to titration is not necessary (why?) • Blank Titration : It is usually carried out to account for the possible reaction of atmospheric moisture with the titrant perchloric acid .+ Hg(CH3COO)2 undissociated HgCl 2 + 2RNH3+ + 2CH3COO- undissociated • However. the counter ion has to be removed prior to titration by addition of mercuric acetate. e. Therefore. and acetate (CH3COO-) is more basic then pyridin (C6H5N). in Erlenmeyer Titration The whole idea of non-aqueous titration is to increase the acidity and basicity for both the solvent and analyte by generating more acidic and basic species. Titration analysis of pyridine (very weak base. i. Titrant solution. CH3COOH2+ is more acidic than HClO4..Non-aqueous Titrations • Example. in Analyte solution. titration of CH3COOH2+ . analyte) dissolved in acetic acid (acidic solvent) titrated with perchloric acid (titrant) dissolved inburett acetic acid. aceton. • 2) amines (weak bases. nbutyl amine. pyridine) or • 3) aprotic solvents (N. t-butyl alcohol). pKa 16 – 20.N-dimethyl formaide (DMF).g. methanol. ethanol. e. methylethayl keton) • which does compete strongly with weak acid for proton donation .g. ethanediamne. e.Non-aqueous Titrations • Non-aqueous titration of weak acids • Solvent: • 1) alcohol (very weak acids. drugs can be titrated directly in a dosage form • If the dosage form is aqueous. Sodium or potassium methoxide (CH3ONa. analyte should be extracted to non-aqueous solvent . CH3OK). tetrabutyl ammonium hydroxide • Generally.Non-aqueous Titrations • Titrant: • Lithium methoxide (CH3OLi). in burett Titration . in Erlenmeyer Titrant solution. analyte) dissolved in DMF titrated with sodium methoxide (titrant) dissolved in methanol. Analyte solution.• Example. Titration analysis of benzoic acid(weak acid. Non-aqueous Titrations • • Practical application Example 1. dried and stored in a vacuum desiccator.69 g / mol).1 M perchloric acid to a blue-green end point. 10 ml of mercuric acetate solution and one drop of crystal violet was added and then titrated with 56 ml of 0. + Hg(CH COO) HgCl + 2CH COO + O N Cl 3 2 2 3 2 2CH 3 COOH2 + + 2CH 3COO From acetous HClO4 From the above rxn 4CH3 COOH O N 2 . 4 g tablet of methacholine cloride (195. Calculate % w/w of methacholine O O cloride. Blank titration was conducted and 1. dissolved in 50 ml of glacial acetic acid.7 ml of perchloloric aid used. Calculate Hthe % w/w of thosuximide. 0. 2 drops of azo-violet solution was added and tirated with 12 ml of 0.Non-aqueous Titrations O • Practical application • Example 2. 0.5 g tablet of Ethosuximide (141.1 N sodium methoxide to a deep blue end point. Na O N O + CH3ONa CH3OH + O N O N ONa .6 ml was needed in blank titration.17 g/mol) dissolved in 50 ml of dimethylformamide. multiplication of this percentage by a suitable factor (6. Since most proteins contain approximately the same percentage of nitrogen.46-mL of 0.05063 M HCI. and 5.00 mL of 0.38 for dairy products. • %N = Mass of N/ Sample mass x 100% • % of crude protein = %N x F . The arnmonia formed was distilled into 50.70 for cereals) gives the percentage of protein in a sample.9092-g sample of a wheat flour was analyzed by the Kjeldahl procedure. Calculate the percentage of protein in the flour.04917 M NaOH. 6.Example for Kjeldahl method • 0. and then back titrated with 7.25 for meats. • Note.