CHAPTER 7: PRECIPITATION AND COMPLEXATION METHODS OF ANALYSIS

*In volumetric precipitimetry a class of reactions is dealt with that

require the formation of relatively insoluble substances or
precipitates to cause the reactions to go to sufficient completion to
be quantitative in nature.

Determination of the End Point

The end point of a reaction in analysis by precipitation methods may
be determined in the following ways:
1.) Cessation of precipitation or the appearance of a turbidity
2.) Use of internal indicators
3.) Instrumental methods,i.e, potentiometric or amperometric

Indicators

The indicators used in the official volumetric precipitation assays

are:
1.) Ferric ammonium sulfate TS
 is prepared by dissolving 8g of reagent ferric ammonium
sulfate in sufficient water to make 100 ml
 this indicator is used both in direct and residual titrations
employing standard ammonium thiocyanate solution
 the thiocyanate reacts with the silver or mercuric ions
present to form a white precipitate of silver or mercuric thiocyanate
but, as soon as all the silver or mercury has been precipitated, the
thiocyanate ion reacts with ferric ammonium sulfate to form a red
ferric thiocyanate
 the first appearance of the RED COLOR marks the end point of
the reaction

2.) Potassium chromate TS

 is prepared by dissolving 10g of reagent potassium chromate in
sufficient water to make 100ml
 it forms a RED PRECIPITATE of silver chromate which is seen
against the background of WHITE SILVER CHLORIDE

3.) Adsorption Indicator

 These indicators are used in the analyses of halides by direct
titration with silver nitrate solution.
 They are weak organic acids that vary in strength so that some
are more effective in acidic media than others
 The end point of the titration is indicated when the color of
the silver halide precipitate changes abruptly because of the adsorbed
indicator anions
***The color changes are best seen in DIFFUSE-LIGHT CONDITION
 a.) Dichlorofluorescein (DCF) TS
 dissolve 100mg of DCF in 60ml of alcohol, add 2.5ml of
0.1N sodium hydroxide, mix, and dilute with water to 100ml

b.) Eosin Y TS
 dissolve 50mg of Eosin Y in 10ml of water

c.) Tetrabromophenolphthalein ethyl ester (TEE) TS

 dissolve 100mg of TEE in 90ml of glacial acetic acid and
dilute with glacial acetic acid to 100ml. Prepare this solution fresh.

STANDARD SOLUTIONS

0.1N silver nitrate & 0.1N ammonium thiocyanate

 standard solutions employed in the official assays by
precipitation methods

EXERCISE 7.1 To Prepare and Standardize 0.1N Silver Nitrate

Ag+  since the univalent silver cation is In a sense a chemical

equivalent of the hydrogen ion
 1 mol of AgNO3 (169.87) is 1 equiv

NOTE: The slow addition of the precipitant, hydrochloric acid, with

continuous stirring of the heated solution aids in the formation of a
precipitate with large particles. The mixture is allowed to stand in
the dark to minimize the reducing effect of the light on the silver
chloride; free silver is produced. The purplish color which the
precipitate acquires on exposure to light is due to the free metal
being formed in the precipitate.

EXERCISE 7.2 To Prepare and Standardize 0.1 N Ammonium Thiocyanate

Ammonium Thiocyanate  is a deliquescent, a slight amount in excess of

the theoretical quantity required is used in preparation of the
solution
 Potassium Thiocyanate (can be used in place of ammonium thiocyanate)
 As the sample of silver nitrate solution is titrated with the
ammonium thiocyanate solution, a white precipitate of AgSCN is formed
 As the end point is approached, the precipitates becomes flocculent
and settles readily
 At the end point, a drop of Ammonium thiocyanate solution produces a
permanent reddish-brown color, which does not disappear on shaking
 Oxides of nitrogen give colored salts with ferric alum. Solutions
containing oxides of nitrogen and also the nitric acid should be
boiled prior to the addition of the indicator.
DIRECT TITRATION METHOD
 Compounds of silver and mercury that can be readily converted into
soluble silver or mercury (Hg2+) salts, respectively, may be estimated
by direct titration with standard ammonium thiocyanate solution, using
ferric ammonium sulfate as indicator.
 The method is based on the quantitative precipitation of the
corresponding thiocyanate
 when all the metallic ion has been precipitated as thiocyanate, the
NH4SCN reacts with the ferric alum indicator to form red ferric
thiocyanate, marking the end point of titration
 the solution must be acidified with nitric acid to prevent the
hydrolysis that ferric salts undergo in neutral solution
 Chlorides must be absent, since the chlorides of silver and mercury
are more soluble than the respective thiocyanates

EXERCISE 7.3 Assay of Phenylmercuric Nitrate for Mercury Content

 the reaction of the sample with the zinc dust in formic acid is such
as to reduce the mercuric ion to free elemental mercury which then
amalgamates with the excess zinc metal
 the amalgam is dissolved in the nitric acid as it is being oxidized
to the bivalent state as Hg2+
 the urea and potassium permanganate ensure that all the mercury is
in the form of mercuric ion
 the excess potassium permanganate is then reduced by the hydrogen
peroxide, and the mercury is ready to be determined with the ammonium
thiocyanate
 the assay for the phenylmercuric compound is performed by a direct
titration reaction of the available mercuric ion with thiocyanate
 In the mercury content assay any and all mercury is converted to
elemental mercury and then oxidized before reacting with thiocyanate
 Mercuric ion does not yield a copious precipitate upon titration
with ammonium thiocyanate as does silver ion
 This is explained by the fact that mercuric thiocyanate Hg(SCN)2,
complexes with the yet unreacted Hg2+
 The presence of halide ions (Cl, Br and I) will interfere with the
determination of mercuric mercury because they too form slightly
dissociated compounds, as does thiocyanate with Hg2+

EXERCISE 7.5 Assay of Iopanoic Acid Tablets

Iopanoic acid  is 3-amino-α-ethyl-2,4,6-triiodobenzenepropanoic acid

 in the degradation of the organic compound by treatment with
zinc and sodium hydroxide the originally bound iodine is converted to
an equivalent amount of iodide ion

EXERCISE 7.6 Assay of Benzyltrimethylammounium Chloride

Dichlorofluorescein  is an adsorptive indicators

  is a weak organic acid and the extent of its ionization is
dependent on the Ph of the titrated solution
 in highly acidic solutions where the Ph is lower than 4, the
anions present are so few as to make the end point very faint
 the Ph of a 1 in 200 solutions of azacyclonol is between 5 and
7
 Alcohol is used in the assay to help keep the precipitated
silver chloride in a colloidal state and thus give sharpness to the
color change which occurs on the precipitate surface

RESIDUAL TITRATION METHOD (VOLHARD METHOD)

 this method is based on the complete precipitation of insoluble
silver salts from nitric acid solution by the addition of excess
standard silver nitrate solution to a soluble salt, and the
determination of the amount of silver nitrate solution in excess by
residual titration with standard ammonium thiocyanate solution, using
ferric ammonium sulfate as the indicator.

EXERCISE 7.7 Assay of Sodium Chloride

Nitric Acid  is added to prevent the precipitation of silver as

carbonate, phosphate, etc., and to prevent hydrolysis of the ferric
alum

Nitrobenzene  is added to form a film over the precipitated silver

chloride particles, thus preventing reaction with the ammonium
thiocyanate

Silver bromide and Silver iodide

 are considerably less soluble
 the precipitate does not interfere in the Volhard analysis of
soluble bromides and iodides

CALCULATIONS:
1.) a 0.2182-g sample of sodium chloride was assayed by the Volhard
method using 50.00ml of 0.0985 N silver nitrate and 11.75ml of 0.1340N
ammonium thiocyanate. Calculate the percent NaCl in the sample.

Given:
Sample: 0.2182g
AgNO3: 50.0 ml & 0.0985 N
AgSCN: 11.75 ml & 0.1340 N
NaCl: mEq.wt: 0.05844

Formula:

% = (mla x N) – (mlb x N) x mEq.wt x 100

Sample wt
Solution:
% = (50.0 x 0.0985) – (11.75 x 0.1340) x 0.05844 x 100
0.2182

% = (4.925 – 1.5745) x 0.05844 x 100

0.2182

% = 89.73

EXERCISE 7.9 Assay of Theophylline

Theophylline
 AKA: 8-chlorotheophylline
 the determination of this substance in official preparations
such as aminophylline, aminophylline injection and tablets,
dimenhydrinate, theophylline tablets, theophylline olamine solution
and theophylline sodium glycinate and tablets is accomplished by the
reaction of theophylline with silver nitrate in a mole-for-mole ratio

SODIUM TETRAPHENYLBORON TITRATIONS

 this method of analysis offers some obvious advantages over previous
methods using alkaloidal precipitants such as potassium ferricyanide
and potassium dichromate and subsequent determination of the excess of
these standard solutions by the addition of potassium iodide and
titrating the liberated iodine with sodium thiosulfate

Sodium tetraphenylboron
 Na(C6H5)4B
 will quantitatively precipitate such organic nitrogen
compounds as alkaloids, amines, and quartenary salts, as well as
ammonium, potassium and silver ions

Quaternary compounds
 it will react with certain dyes such as bromophenol blue, an
anionic dye, to form a blue, chloroform-soluble complex and this
colored complex will react with sodium tetraphenylboron to form an
insoluble compound

COMPLEXATION METHODS

INTRODUCTION
 the quantitative analysis of inorganic pharmaceutical products
containing metal ions such as Al, Bi, Ca, Mg and Zn was performed
using gravimetric methods
 these procedures were very time-consuming, since they involved
precipitation, filtration, washing, and drying or ignition to constant
weight
 official calcium preparations were later analyzed volumetrically
using an oxalate-permanganate procedure which involved a precipitation
technique and titration of a carefully heated solution of oxalate ions

Disodium ethylenediaminetetraacetate
 C10H14N2Na2O8.2H2O
 commonly reffered as EDTA
 an analytical reagent used in a new volumetric procedure
evolved for metal determination employing metal-ion indicators in the
same manner that pH indicators are used in acid-base titrations
 has a molecular weight of 372.24
 consequently, a 1/20 M solution would contain 372.24/20 or
18.612g dissolved in 1 liter of solution
 the water should be metal-free; therefore, glass-distilled
water is preferred
 Solutions are best stored in polyethylene containers or in
glass containers previously prepared by boiling the container in an
alkaline 2% solution of EDTA to remove any metal ions

Disodium salt  is preferred over the free acid in preparing the

standard solution of EDTA
 it is much more water-soluble, nonhygroscopic and very stable

COMPLEXATION REACTION

COMPLEX  when a metal ion combines with a molecule which can donate
electrons

CHELATE  this complex wherein combining molecule contains two or more

groups that donate electrons
 EDTA will react with metal ions to form a water-soluble,
stable complex or chelate compound
 the reaction is rapid and quantitative with such POLYVALENT
METAL IONS as Al3+, Bi3+, Ca2+, Cu2+, Hg2+, Mg2+ and Zn2+

Monovalent metal ions  are relatively weak or unstable

complexes

Bivalent metal ions  such as calcium or magnesium

 there are six bonds or points of attachment between
the metal and the EDTA, of which two are ionic and two are ordinate
bonds both involving the oxygen atoms, and two are coordinate bonds
formed by the unshared pair of electrons of the nitrogen atoms which
are donated to the metal

Trivalent metal ions  such as Al3+

 one of the ordinate bonds would then become ionic
in character
 Hexadentate molecule  the four oxygen and the two nitrogen
atoms of the EDTA molecule capable of entering a complexation reaction
with a metal ion

Ligand  the EDTA molecule which provides groups for attachment

to metal ions
*** EDTA-metal complexes are very stable, since the five-
membered rings formed in the complex are stain-free and are the most
stable rings involving organic molecules

Solubility Product Constant  it is formed when the equilibrium

constant of the reaction applied to the insoluble compound
 in gravimetric method of analysis, the formation of a
precipitate was a sufficient driving force to cause a reaction to go
far to the right, or to completion

Ionization constant  it is formed when the equilibrium

constant of the reaction applied to the slightly dissociated product,
H2O
 In acidimetry-alkalimetry, the formation of a very
slightly ionized water was the driving force in the neutralization
reaction

Stability Constant  the application of the law of mass action

to the reaction equilibrium
 In a complexometric reaction, the formation of a stable,
soluble complex is the driving force in the reaction
 is a large number since the complex is very slightly
ionized and the concentration of the calcium-EDTA complex is so much
greater than its constituent ions

The Factors influencing the EDTA reaction:

a.) the activity of metal ion
b.) the pH at which the titration is run
c.) the presence of interfering ions such as cyanide, citrate,
tartrate, fluoride, and other complex-forming agents

NOTE!!
*** the higher the stability constant, the more acid the pH at which
the complexation titration can be run
*** Organic Solvents also increase the stability of the complex
*** Neutral Salts such as NaCl decrease the stability

EDTA titration indicators

 are organic compounds which form colored complex ions with
the metal ion in high dilution

The qualities of a Good Indicator:

1.) Sharpness of color change at the end point
2.) Specificity of the indicator for the metal ion under the
conditions of the analysis
3.) Stability constant smaller than that of the metal-EDTA complex,
i.e., the indicator must give up the metal ion to the titrant EDTA for
complexing and not compete with it

The end point may be sharpened by the addition of a nonchelating

screening dye that is complementary to the color observed either just
before or just after the end point is reached.
 ex: azo dyes, phthaleins, triphenylmethane dyes,etc

* Eriochrome black T
 the colored form are RED, BLUE and YELLOW-ORANGE
 this dye is sensitive to changes in metal concentration as
well as to changes in Ph
RED COMPLEXES are formed with Mg2+, Zn2+ and many other metals,
such as Al, Ca, Pb, and Hg

MASKING  this term is used to indicate the determination of a metal

in the presence of another metal
 capable of entering a complexation reaction
 can be accomplished by adjusting the Ph of the titration
medium so that it will be favorable for complexation of the metal
being determined and not of the other metal
 Auxiliary complexing agents also serve as masking agents
 Ascorbic acid, citrates and tartrates are also used as
masking agents

Bi  will complex at Ph 2 in in the presence of most other

metals and without interference from them
 DITHIZONE indicator used
Zn  will not interfere with Ca titration at a Ph of 13
Triethanolamine  will impart enough alkalinity to suppress Al-
EDTA complexation in the presence of a Mg-EDTA reaction and also serve
as a ligand with its unshared pair of electrons
Thioglycols  will inactivate metals such as Hg and Cu which
react with the sulfhydryl groups, thus allowing the titration of Zn at
Ph 6
Potassium cyanide  can be used to inactivate or mask or screen
such metals as Co, Ni, Cu and Zn
Ammonium fluoride  will mask Ca, Mg and Al to allow titration
of Zn

EXERCISE 7.12 Determination of the Bismuth Content of Glycobiarsol

The amines titrated with dioctylsodium sulfosuccinate are:

a.) Dicyclomine hydrochloride preparations such as capsules,

injection, syrup and tablets
b.) cetylpyridinium chloride lozenges
c.) methylbenzethonium chloride powder, lotion and ointment
Tetrabutylammonium iodide  is the titrant used to determine
dioctylsodium sulfosuccinate , capsules and solution, as well as
dioctylcalcium sulfosuccinate

FERRIC CHLORIDE TITRATION

Sodium fluoride determination  is based on the reaction of sodium
fluoride with ferric chloride to form a reasonably stable complex of
the type FeF63-
 indicator used are phenolphthalein and potassium thiocyanate