Lab Manual Quantitative Analytical Method by Deepak Pant (red novels .TXT) 📕

titrated with acetous perchloric acid. The various reactions which occur are given as follow: Acetic acid alone behaves as a weak acid, because of poor dissociation into H +
CH3COOH ↔ CH3COO ̄ + H +
But when a strong acid (Perchloric acid) is added to acetic acid, there is formation of Onium ions, which has more tendency to donate protons.
HClO4 <-> H+ + ClO4 ̄
CH3COOH + H+ <-> CH3COOH2+
(Onium ion)
When weak bases like pyridine are dissolved in acetic acid, equivalent amount of acetates ions are produced which have more tendency to accept protons.
C5H5N + CH3COOH <-> C5H5NH+ + CH3COO ̄
Ultimately, the titration of weakly basic drug in acetic acid against acetous perchloric acid yields accurate end point. The series of reactions are given as follows:
HClO4 + CH3COOH -> CH3COOH2+ + ClO4 ̄
C5H5N + CH3COOH -> C5H5NH+ + CH3COO ̄
(Acetate ions)
CH3COOH2 + CH3COO ̄ -> 2CH3COOH
(Burette) (Conical flask)
The net reaction is given as
HClO4 + C5H5N -> C5H5NH+ + ClO4 ̄
Thus we have seen that, on one hand the tendency of acid to donate proton is increased and on the other hand, the tendency of base to accept proton is increased. These leads to the sharp end point in non –aqueous titrations.


Table: Acidimetric Assays: Non-aqueous Titrations with Perchloric Acid using Mercuric Acetate and different Indicators:
S.No. Name of Substance
Indicator Employed

1. Amantadine hydrochloride
Crystal violet
2. Chlorpromazine hydrochloride
Methyl orange
3. Clonidine hydrochloride
α -Naphthol benzein
4. Cyproheptadiene.HCl
Crystal violet
5. Dehydroemetine.HCl
-do-
6. Ephedrine hydrochloride
-do-
7. Imipramine hydrochloride
-do-
8. Isoprenaline hydrochloride
Crystal violet
9. Lignocaine hydrochloride
-do-
10. Morphine hydrochloride
-do-
11. Morphine sulphate -do-
12. Phenylephrine hydrochloride
-do-
13. Phenytoin sodium α -Naphthol benzein
14. Promethazine hydrochloride
Methyl orange
15. Thiabendazole Crystal violet

REQUIREMENTS FOR THE TITRATION OF WEAK BASES WITH PERCHLORIC ACID Following points should be considered:
1. Titrant used.
2. Preparation of 0.1N (HClO4) and it standardization.
3. Solvent used.
4. Practical examples of Indicators.

Titrant used: Solution of HClO4 in either glacial acetic acid or dioxane solution is used for titration of weak bases. Generally HClO4 with a normality of 0.1N to 0.05N is used.
Preparation of 0.1N solution of HClO4 and its standardization: Dissolve 8.5 ml of 72% HClO4 in about 900 ml glacial acetic acid with constant stirring, add about 30 ml acetic anhydride and make up the volume (1000 ml) with glacial acetic acid and keep the mixture for 24 hour. Acetic anhydride absorbed all the water from HClO4 and glacial acetic acid and renders the solution virtually anhydrous. HClO4 must be well diluted with glacial acetic acid before adding acetic anhydride because reaction between HClO4 and acetic anhydride results in the formation of acetyl perchlorate which is an explosive. Standardization of 0.1N Perchloric acid: Weigh accurately 0.7g of potassium hydrogen phthalate (primary standard), previously powdered light and dried for 2 hours and dissolve it in 50 ml of glacial acetic acid. Add few drops of crystal violet solution as indicator and titrate with perchloric acid solution until the violet colour changes to emerald green. Perform a blank titration by using 50 ml of glacial acetic acid and subtract the volume of perchloric acid consumed (crystal violet -0.5% w/v in acetic acid). Each ml of 0.1N Perchloric acid ≡ 0.02042 g of Potassium hydrogen Phthalate

Strength of 0.1N Perchloric acid = wt. of potassium hydrogen phthalate taken / Vol. of Perchloric acid X 0.02042
204.2g of C8H5O4K ≡ 1N 1000 ml HClO4
0.02042g of C8H5O4K ≡ 1 ml of 0.1 N HClO4
Solvent used: Glacial acetic acid alone or sometimes in combination with some aprotic solvents is often used. The other solvents are CHCl3, benzene, chloro benzene, acetic anhydride and various combinations of these sometime glycohydrocarbon mixtures are also used. Indicators used: Crystal violet 0.05% w/v in glacial acetic acid, methyl red 0.1% w/v in anhydrous methanol, oracet blue 0.5% w/v in glacial acetic acid.
EXPERIMENT TITRATION OF HALOGEN ACID SALTS OF BASES WITH PERCHLORIC ACID
In general, the halide ions, namely: chloride, bromide and iodide are very weakly basic in character so much so that they cannot react quantitatively with acetous perchloric acid. In order to overcome this problem, mercuric acetate is usually added (it remains undissociated in acetic acid solution) to a halide salt thereby causing the replacement of halide ion by an equivalent amount of acetate ion, which serves as a strong base in acetic acid as shown below:
2R.NH2.HCl <->2RNH3 + + 2Cl –
CH3COO) 2 Hg + 2Cl- ->HgCl2 + 2CH3COO-
(Undissociated) (Undissociated)
2CH3COOH2+ + 2CH3COO- <-> 4 CH3 COOH

NON –AQUEOUS TITRATIONS OF WEAKLY ACIDIC SUBSTANCES
There are several drugs which are weakly acidic. Such substances can be titrated against strong bases like potassium methoxide, sodium methoxide, lithium methoxide, tetra butyl ammonium hydroxide, etc in solvents like toluene- methanol. The principle is similar to the titration of weak bases against perchloric acid.
Table: Alkalimetric Assays: Non-Aqueous Titrations using Lithium Methoxide/Sodium Methoxide either Potentiometrically or Titrimetrically
S.No. Name of Substance
Indicator Employed

1. Acetazolamide Potentiometric determination

2. Bendrofluazide Azo violet
3. Allopurinol Thymol blue

4. Mercaptopurine -do-

5. Amylobarbitone Quinaldine Red

6. Nalidixic acid Thymolphthalein


Preparation of 0.1 N Potassium Methoxide in Toluene-Methanol:
Material Required: Absolute methanol, dry toluene, Potassium metal.
Preparation of 0.1 N Sodium Methoxide: It is prepared exactly in a similar manner as for
Procedure: Add into a dry flask, a mixture of methanol (40 ml) and dry toluene (50 ml) and cover it loosely. Carefully add freshly cut pieces of potassium metal (5.6 gm) to the above mixture gradually with constant shaking. After complete dissolution of potassium metal, add enough absolute methanol to yield a clear solution. Toluene 50 ml is added with constant shaking until the mixture turns hazy in appearance. The process is repeated by the alternate addition of methanol and benzene until 1 litre of solution is obtained, taking care to add a minimum volume of methanol to give a visible clear solution. 0.1 N Potassium Methoxide, using 2.3g of freshly cut sodium in place of potassium.
Preparation of 0.1 N Lithium Methoxide: It is prepared as for 0.1 N Potassium Methoxide, but using 0.7 g of lithium in place of potassium.
Standardization of 0.1 N Methoxide Solution
Material Required: Dimethylformamide (DMF): 10 ml; thymol blue (0.3% in MeOH); 0.1 N lithium methoxide in toluene methanol; benzoic acid: 0.6 g.
Procedure: Transfer 10 ml of DMF in a conical flask and add to it 3 to 4 drops of thymol blue and first neutralize the acidic impurities present in DMF by titrating with 0.1 N lithium methoxide in toluene-methanol. Quickly introduce 0.06g of benzoic acid and titrate immediately with methoxide in toluene-methanol.
Equations: The various equations involved in the above operations are summarized as stated below:
i) Na + CH3OH → CH3ONa + H↑
Interaction between sodium metal and methanol is an exothermic reaction and hence, special care must be taken while adding the metal into the dry solvent in small lots at intervals with adequate cooling so as to keep the reaction well under control.
(ii) H2O + CH3ONa → CH3OH + NaOH
H2CO3 + 2CH3ONa → 2CH3OH + Na2CO3
The clear solution of sodium methoxide must be kept away from moisture and atmospheric CO2 as far as possible so as to avoid the above two chemical reactions that might ultimately result into the formation of
turbidity.
(iii) C6H5COOH + H—CON (CH3)2 ↔ HCON+H (CH3)2+C6H5COO - ------1
(DMF)
CH3ONa ↔ CH3O- + Na+ --------------------------------------------------------2
HCON+H (CH3)2 + CH3O - → HCON (CH3)2 + CH3OH -------------------3
Summing up: C6H5COOH + CH3ONa → C6H5COONa + CH3OH
Step 1: It shows the solution of benzoic acid (primary standard) in DMF,
Step 2: It depicts ionization of sodium methoxide,
Step 3: It illustrates the interaction between the solvated proton and the methylated ion.
summing up, the net reaction between the water in the solvent (DMF) and the titrant is equivalent to the volume of sodium methoxide consumed by DMF or may be considered as a blank determination.
N/10 KOH in Methanol Dissolve 5.6 gm of anhydrous KOH in 1000 ml of anhydrous methanol. This titrant is not as powerful as others. Its main disadvantage is that it reacts with acidic functional groups and produces a molecule of water, which would affect the sensitivity of titration.
Standardisation:
All these titrants are usually standardized against standard benzoic acid AR-Grade. A sufficient amount of benzoic acid which would give a titrate value of 20-30 ml is transferred in a dry flask and dissolved in 25 ml dimethylformamide, 2-3 drops of 0.5% thymol blue indicator in dry methanol is added to the solution. A blank titration is also per formed in the solvent to account acidic impurity in dimethylformamide and the correction is made accordingly.
Tetrabutylammonium Hydroxide The alkalimetry in non-aqueous titrations may also be carried out efficiently by using tetrabutylammonium hydroxide along with an appropriate indicator.
Preparation of 0.1 N Tetrabutylammonium Hydroxide in Toluene-Methanol Materials Required: Tetrabutylammonium iodide: 40 g; absolute methanol: 90 ml; silver oxide: 25 g; dry toluene: 150 ml.
Procedure: Carefully dissolve 40 g of tetrabutylammonium iodide (Bu4 NI) in 90 ml of absolute methanol, add to it 20 g of finely powdered purified silver oxide and finally shake the mixture thoroughly for 1 hour. Centrifuge about 2-3 ml of the resultant mixture and test for iodide in the supernatant liquid. In case, it gives a positive test, add about 2 g more of silver oxide and shake for an additional period of 30 minutes. The said method may be repeated until the supernatant liquid obtained is completely free from iodide. The mixture thus obtained is filtered through a fine sintered glass filter and finally rinse the container with 3 portions, each of 50 ml of dry toluene. These washings may be added to the filtrate and the final volume is made up to 1 litre with dry toluene. The clear solution should be kept duly protected from both CO2 and moisture during storage.
Equation:
2Bu4NI + Ag2O + H2O -> 2Bu4NOH + 2Agl
Tetra butyl- Tetra butyl-
Ammonium Iodide ammonium hydroxide
Precautions:
Following points should be considered:- Moisture and CO2 have to be excluded, water being weakly basic would compete with perchloric acid and sharpness of end point would be lost, therefore, moisture contents should be less that 0.05%. The presence of CO2 affects basic solvent like Dimethyleformamide, ethylene diamine and pyridine as they adsorb CO2 from air.
• During preparation of Perchloric acid it must be well diluted with acetic acid before adding the acetic anhydride to prevent the formation of explosive acetyl per chlorate.
• Do not use a solvent until fully acquainted with its hazards and how to use it safely.

REFERENCE:
1. K A Conners, A Text Book of Pharmaceutical Analysis, Wiley-Intersciences, New York.
2. A H Backett and J B Stenlake, Practical Pharmaceutical Chemistry, Vol.I and II, The Athlone Press of The University of London. 3. Pharmacopoeia of India, Govt.of India, Ministry of Health, Delhi.