nonaqueoustitration HGKTFKHFUYGUYGUYG.pptx

NON AQUEOS TITRATION

1. Presented by:- TALHA SHAHID PHARMACEUTICAL ANALYSIS Non Aqueous Titration

2. NON-AQUEOUS TITRATIONS PRINCIPLE:- The organic acids and bases are insoluble in water. these are extremely weak and cannot be analysed using normal titrimetric methods. hence the non aqueous titrimetric methods are employed. The main principle involved in the non aqueous titrimetric methods is the samples are dissolved in non aqueous solvents.

3. Why Non aqueous titration:- These are employed due to the three vital problems of quality control, both in pure and dosage forms by virtue of their inherent characteristics, namely:- (a) Reactants are insoluble in water or poor solubility. (b) Reactants are weak reactive in aqueous medium. (c) Reactants are very weak acidic and weak basic in nature. Pka value >7 - weak Acid Pka value <7 - weak base

4. Initially, the above three problems were usually avoided in the following manner:- 1: - Amine salts:- It is first changed to the water-soluble free base, extracted with an appropriate organic solvent and treated with an excess volume of standard acid subsequently, the solvent was evaporated, and the remaining acid determined with a standard base. 2:- Sodium salts:- It is first acidified to release the water-insoluble organic acid, extracted with a suitable organic solvent, the solvent was removed and the residue was subsequently dried and weighed. 3:-Nitrogen containing compounds:- They are estimated by micro Kjeldahl’s Method. Nevertheless, such specific quantitative methods gave rise to certain serious anomalies and drawbacks.

5. ADVANTAGES OF NON-AQUEOUS TITRATIONS:- • Elimination of poor solubility of organic acids and bases that are insoluble in water. • Enhancement of weak reactivity of substances. • Selective titration by using suitable solvent and titrant of acidic/basic components of physiologically active moiety of a salt. • Weak bases which have Kb values less than 10 –6 can be titrated by using non-aqueous titrations.

6. THEORY:- According to Bronsted - Lowry theory the various reactions that take place during many non-aqueous titrations. Where, an acid is a proton donor and a base is a proton acceptor. Therefore, when an acid [HA] undergoes dissociation it gives rise to a proton and the conjugate base [A] of the acid:- HA H + + A -

7. SOLVENTS:- These are of four types and they will be discussed briefly here:- ( i ) Protophillic Solvents:- (ii) Protogenic Solvents:- (iii) Amphiprotic Solvents:- (iv) Aprotic Solvents:- a) Polar Aprotic Solvents b) Non Polar Aprotic Solvents

8. ( i ) Protophillic Solvents:- The words “proto” means proton and “ phillic ” means loving. The solvent which accept proton is called as protophillic solvents. They are essentially basic in nature and normally react with acids to form solvated protons:- HA + Sol. Sol. H + + A – Example:-Liquid ammonia, NaOH , KOH, NH 4 OH 1. Levelling effect:- Effect of protophillic solvents on the properties of acids and bases 2. Differentiating effect:-

9. Levelling effect:- In leveling solvents, several acids are completely dissociates and having same strength. Weak acids are normally used in the presence of strongly protophilic solvents(Strong Base) as their acidic strengths are then enhanced and then become comparable to these of strong acids; this is known as the levelling effect. In other words, strong protophillic solvents convert weak acid to strong acid is known as Levelling effect. Generally stong bases are exert as lavelling solvents for strong acid as well as weak acid. Example:- H 2 0 is act as levelling solvent for HCl and HBr .

10. Differentiating effect:- In differentiating solvents, several acids are dissociates to different degrees and having different strength. Generally weak bases are exert as differentiating solvents for strong acid as well as weak acid. Example:- H 2 0 is act as differentiating solvent for HF.

11. (ii) Protogenic Solvents:- The words “proto” means proton and “ genic ” means generate. The solvent which generate or donate proton is called as protogenic solvents. They are acidic in nature. Example:- Anhydrous acids such as HF, H 2 SO 4 , HCl , HBr , HClO 4 etc.

12. (iii) Amphiprotic Solvents: - They possess both protophillic and protogenic characteristics. These type of solvents able to donate protons as well as accept protons. Examples:- Acetic acid, water and alcohols. They undergo dissociation to a very less extent. Acetic acid is mostly employed as a solvent for the titration of basic substances and its dissociation can be depicted as shown below:- CH 3 COOH H + + CH 3 COO – In the above instance acetic acid is behaving as an acid.

13. (iv) Aprotic Solvents:- These type of solvents neither donate protons nor accept protons. Aprotic solvents include those substances, which may be considered chemically neutral, and virtually un-reactive or inert. These may be fall in two types:- a) Polar Aprotic Solvents:- Acetone, DMSO(Di methyl sulfoxamide ) b) Non Polar Aprotic Solvents:- Benzene, Toluene, Hydrocarbon Aprotic solvents are frequently used to dilute reaction mixture.

14. METHODOLOGY For non-aqueous titrations, the following four steps are usually taken into consideration, namely:- ( i ) Preparation of 0.1 N Perchloric acid, (ii) Standardization of 0.1 N Perchloric Acid, (iii) Choice of Indicators (iv) Effect of Temperature on Assays.

15. PREPARATION OF 0.1 N PERCHLORIC ACID Procedure:- Gradually mix 8.5 ml of perchloric acid to 900 ml of glacial acetic acid with vigorous and continuous stirring. Now add 30 ml acetic anhydride and make up the volume to 1 litre with glacial acetic acid. Allow to stand for 24 hours before use.  

16. Procedure:- Weigh accurately about 0.5 g of potassium hydrogen phthalate in a 100 ml conical flask. Add 25 ml of glacial acetic acid and attach a reflux condenser fitted with a silica-gel drying tube. Warm until the salt gets dissolved completely. Cool and titrate with 0.1 N perchloric acid by making use of any indicators observed end point (a) Crystal violet:- Blue to Blue-Green (b) Oracet blue B:- Blue to Pink.

17. ASSAY BY NON-AQUEOUS TITRATIONS Non aqueous titrations can be categorized into two class:- ( i ) Acidimetry in Non-aqueous Titrations (ii) Alkalimetry in Non-aqueous Titrations Fill the titrant in the Burette. Take analyte & indicator in Conical Flask Add titrant drop wise to the analyte with use of indicator Titrant neutralize the analyte or is visibly spotted by the use of indicators.(End Point) When completely neutralize the analyte (equivalent Point)

18. Acidimetry in Non-aqueous Titrations:-  It is used for quantitative estimation of basic drugs. Titrant used in acidimetry is acidic in nature like Perchloric acid. Solvents:- Protogenic solvents are used like Glacial acetic acid. Indicators:- Crystal violet (End point observed as violet to light green). Application:- It may be used for analysis of Ephedrine, Morphine, Adrenaline, Acyclovir and Caffeine.  It can be further sub-divided into two heads, namely as:- ( i ) Titration of primary, secondary and tertiary amines like Methlyldopa . (ii) Titration of halogen acid salts of bases.

19. (ii) Alkalimetry in Non-aqueous Titrations:-   It is used for quantitative estimation of acidic drugs. Titrant used in alkalimetry is basic in nature like sodium methoxide (CH 3 COONa). Solvents:- Protophillic solvents are used like DMF( Dimethyl formamide ). Indicators:- Thymol blue (End point observed as Pink to blue). Application:- It may be used for analysis of Nalidixic acid, Acetazolamide , Allopurinol , Mercaptopurin .

20. ESTIMATION OF EPHEDRINE HYDROCHLORIDE Assay Procedure:- Weigh accurately about 0.17 g of Ephedrine Hydrochloride, dissolve in 10 ml of mercuric acetate solution, warming gently, add 50 ml of acetone and mix. Titrate with 0.1 M perchloric acid, using 1 ml of a saturated solution of methyl orange in acetone as indicator, until a Red Colour is obtained.   Where, X ml = Volume of titrant consumed at end point Normality Calculated = Normality of Perchloric acid after standardization Normality Given = 0.1 N (theoretically)   Equivalent or I.P factor: - 1 ml of 0.1 M perchloric acid is equivalent to 0.02017 g of C 10 H 15 NO.HCl.

21. ESTIMATION OF SODIUM BENZOATE Assay Procedure:- Weigh accurately about 0.25 g of Sodium Benzoate, dissolve in 20 ml of anhydrous glacial acetic acid, warming to 50º if necessary, cool. Titrate with 0.1 M perchloric acid, using 0.05 ml of 1-naphtholbenzein solution as indicator. Equivalent or I.P factor: - 1 ml of 0.1 M perchloric acid is equivalent to 0.01441 g of C 7 H 5 NaO 2 . Where, X ml = Volume of titrant consumed at end point Normality Calculated = Normality of Perchloric acid after standardization Normality Given = 0.1 N (theoretically)

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