Non aqueous titration
Titration in water solutions is limited by factors:
▶ It is impossible to titrate for a mix of acids or the bases
▶ It is impossible to titrate for a mix of strong and weak
acids (bases)
▶ It is impossible to titrate separately for a mix of acids
(bases) with near constants of dissociation
▶ It is impossible to define substances which are insoluble
in water.
Non- aqueous titrations have the
following advantages
▶ Organic acids and bases that are insoluble in water are soluble in non-
aqueous solvent.
▶ A non-aqueous solvent may help two are more acids in mixture. The
individual acid can give separate end point in different solvent.
▶ Enlargement of solubility range: many substances that are not soluble
in water can be easily titrated in water-free media (e.g. fats and oils)
▶ Enlargement of application range: weak bases and acids can be easily
titrated
▶ Substance compositions that cannot be separately determined
in aqueous media can often be titrated in non-aqueous media
▶ Non-aqueous solvents are useful for the titration of very weak acids
or bases that cannot be titrated in water
▶ Non aqueous titrations are simple and accurate, examples of
non aqueous titration are :
▶ Ephedrine preparations, codeine phosphate in APC,
tetracycline, teramycin, Anti- histamines and various piprazine
preparations.
• Solvent which are used in non aqueous titration are called
non aqueous solvent.
• They are following types:-
1. Aprotic Solvent
2. Protogenic Solvent
3. Protophillic Solvent
4. Amphiprotic Solvent
• Aprotic solvent are most important solvent in this titration. This solvent are
chemically inert and they work as a catalyst. Like this solvent are increase
the rate of speed in reaction and also decrease the rate of speed in reaction
during the chemical process or reaction it will depend on condition.
• Neither acidic nor basic (inert solvent),
The most important examples of aprotic solvent are
• Chloroform
• Benzene
▶ Protogenic solvent are acidic in nature. And they
can donate the proton, and they enhance the
strength of weak
bases. Examples of Protogenic solvent are
▶ HCL
▶
H2so4
▶ Protophillic solvent are basic in nature. Which
possess a high affinity for proton.
Examples:-Liquid ammonia, amines and ketone.
▶ Amphiprotic solvent are those solvent they work
as a both mean Protogenic or Protophillic. It
means Amphiprotic solvent are acidic and basic in
nature. And they are accept the proton and donate
the proton.
For examples:- Water, Alcohols and weak organic
acids
• Visual indicator are formed to the most suitable for the detection
of end point in non-aqueous titration.
• The important indicator used for non-aqueous titration are
follow:-
1. Crystal voilet:- It is used as 0.5% solution in glacial acetic
acid, it gives voilet colour in basic medium and yellowish
green in acidic medium.
• It is most widely use for the titration of pyridine with
prechloride acid.
2. Oracet Blue B Indicator:- It is prepared o.5% glacial
acetic acid. It gives blue colour in basic medium while
pink colour in acidic medium.
Acetic acid used for titration of weak bases,
Nitrogen containing compounds
Acetonitrile / with ACOH: Metal ethanoates
Alcohols (IPA, nBA) : Soaps and salts of organic
acids,
DMF: Benzoic acid, amides etc
▶ Perchloric acid in acetic acid
◦ Amines, amine salts, amino acids, salts of acids
▶ Potassium Methoxide in Toluene-Methanol
▶ Quan ammonium hydroxide in Acetonitrile-
pyridine
◦ Acids, enols, imides & sulphonamides
▶ Acidimetry in Non-aqueous Titrations— It
can be further sub-divided into two heads, namely :
(i)Titration of primary, secondary and tertiary amines,
and
(ii) Titration of halogen acid salts of bases.
▶ Alkalimetry in Non-aqueous
Titrations — titration of acidic substances
Example : Primary
amines
METHODOLOGY: four steps
▶ (i) Preparation of 0.1 N Perchloric acid,
▶ (ii) Standardization of 0.1 N Perchloric Acid,
▶ (iii) Choice of Indicators, and
▶ (iv) Effect of Temperature on Assays
▶ Materials Required : 8.5 ml of perchloric acid (70.0 to 72.0%)
; 1 Litre of glacial acetic acid ; 30ml of acetic anhydride.
▶ 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 glacialacetic acid and allow to stand for 24 hours before
use.
▶ The acetic anhydride reacts with the water (approx. 30%) in
perchloric acid and some traces in glacialacetic acid thereby
making the resulting mixture practically anhydrous. Thus, we
have :
H2O + (CH3CO)2O → 2CH3COOH
Acetic anhydride Acetic acid
▶ 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 either of
the following two indicators :
▶ (a) acetous crystal violet-2 drops, end point Blue to
Blue-Green (0.5% w/v)
▶ (b) acetous oracet blue B-2 drops, end point Blue to
Pink.
S.No. Name of Indicator Colorchange Observed Acidic
Basic
Neutral
1 Crystal violet (0.5% w/v Violet Bluish Yellowish
in glacial acetic acid) green green
2 Oracet Blue B(0.5% in Blue Purple Pink
glacial acetic acid)
3 α-Naphtholbenzein Blue Orange Dark-
(0.2% in glacial acetic green
acid —
Magenta
4 Quinalidine Red Almost
(0.1% in methanol colourless
(a) Perchloric acid is usually available as a 70 to 72% mixture with
water .It usually undergoes a spontaneous explosive decomposition
and, therefore, it is available always in the form of a solution.
(b) Conversion of acetic anhydride to acetic acid requires 40-45
minutes for its completion. It being an exothermic reaction, the solution
must be allowed to cool to room temperature before adding glacial
acetic acid to volume,
(c) Avoid adding an excess of acetic anhydride especially when
primary and secondary amines are to be assayed, because these may
be converted rapidly to their corresponding acetylated non-basic
products :
R— N H2 + (CH3CO)2O → R.NH.(CH3CO) +
Primary amine
CH3COOH Acetylated product
(d) Perchloric acid is not only a powerful oxidising agent but also a
strong acid. Hence, it must be handled very carefully.
S.No. Name of Substance Indicator Employed
1 Amantadine Crystal violet
hydrochloride
Chlorpromazin Methyl orange
2 e
hydrochloride
3 Clonidine hydrochloride α -Naphthol benzein
4 Cyproheptadiene.HCl Crystal violet
5
Ephedrinehydrochlorid -do-
e
Preparation of 0.1 N Potassium Methoxide in Toluene-Methanol
Materials Required: Absolute methanol : 40 ml ; dry toluene : 50 ml ; potassium
metal : 4 g.
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 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.
Preparation of 0.1 N Sodiun Methoxide
It is prepared exactly in a similar manner as for 0.1 N Potassium Methoxide, using 2.3 g 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
Materials 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 0.06 g of benzoic acid and titrate immediately with Methoxide in toluene
methanol.
Caution: Care must be taken to avoid contamination of neutralized liquid with atmospheric carbon
dioxide.
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.
H2O + CH3 ONa → CH3OH + NaoH
H2CO3 + 2CH3ONa → 2CH3OH + Na2CO3
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 (Bu4NI) 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 may
be flushed with CO2-free nitrogen for at least five minutes and duly protected from both CO2 and
moisture during storage.
2Bu4NI + Ag2O + H2 O → 2Bu4NOH + 2AgI
Tetrabutyl- Tetrabutyl ammonium
ammonium hydroxide
bromide
Standardization of 0.1 N Tetrabutylammonium Hydroxide
Materials Required : Benzoic acid : 60 mg ; dimethylbromide : 10 ml ;
thymol blue solution (0.3% w/v in methanol) ; 0.1 N tetrabutylammonium
hydroxide.
Procedure: Accurately weigh about 60 mg of benzoic acid into 10 ml of
previously neutralized Dimethyl formamide to the blue colour of thymol blue
(3 drops) by titration against 0.1 N tetrabutylammonium hydroxide.
Allow the benzoic acid to dissolve gradually and completely and titrate with
0.1 N tetrabutylammonium hydroxide.
0.01221 g C7H6O2 ≡ 1 ml of 0.1 N
