PharmAnal 2

Lecture 2
Analytical
Chemistry:
NEUTRALIZATION
PHARMACEUTICAL ANALYSIS I
Quantitative Pharmaceutical Chemistry
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OBJECTIVES
1. To discuss the fundamental concepts of analytical chemistry and its applications in quality
control
2. To discuss the errors in analytical chemistry
3. To define important terms related to titrimetric analysis
4. To review basic concepts on chemistry and calculations
5. To enumerate the types of titration
6. To define neutralization reactions and apply its concepts to sample problems
7. To give examples of titrations involving neutralization reactions
8. To identify the commonly used indicators
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OUTLINE
1. Analytical Chemistry
2. Errors in Analytical Chemistry
3. Titrimetric Analysis
a. Important Terms
b. Types of Titration
c. Types of Reactions in Titrimetric Analysis
4. Neutralization Reactions
a. Review of Concepts
b. Classification
c. Indicators
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ANALYTICAL
CHEMISTRY
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ANALYTICAL CHEMISTRY
DEFINTION
Area of chemistry responsible for characterizing the composition of matter, both qualitatively
and quantitatively (Classical definition)
Science of inventing and applying concepts, principles and strategies for measuring the
characteristics of chemical systems and species (Modern definition)
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MAJOR DIVISIONS
QUALITATIVE ANALYSIS QUANTITATIVE ANALYSIS
• WHAT is present • HOW MUCH is present
• Identification of components in a given • Determination of amount of components
sample in a given sample
• Reveals the chemical identity of species in
the sample
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C L A S S I F I C AT I O N O F A N A LY S I S
1. Based on extent of determination
2. Based on sample size
3. Based on material used
4. Based on nature of method
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Based on extent of determination
• Total amount of a group or class of compounds
PROXIMATE ANALYSIS • Deadly nightshade (belladona): alkaloid
• Peppermint: volatile oil

• Total amount of a specific compound
ULTIMATE ANALYSIS • Deadly nightshade (belladona): atropine
• Peppermint: menthol
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Based on sample size
ULTRA MICRO < 1 mg

MICRO 1 mg – 10 mg
SEMI MICRO 10 mg – 100 mg
MACRO 100 mg – 1 g
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Based on material used
CHEMICAL Use reagents

BIOLOGICAL Use living systems
PHYSICAL Use instrument or apparatus
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Based on nature of method
Stoichiometric
Based on chemical reactions
CLASSICAL Analyte and another substance which would yield a product
Titrimetry, gravimetry
Based on physical, chemical properties of analyte
INSTRUMENTAL Spectrophotometry, polarimetry, chromatography,
refractometry
Deals with crude drugs or natural products
MISCELLANEOUS/SPECIAL Ash content, acid value, water content
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INTERNATIONAL CONFERENCE ON HARMONISATION (ICH) GUIDELINES
The ICH was initiated in Brussels in 1990 and brought together representatives of regulatory
agencies and industry associations of Europe, Japan and the USA.
PURPOSE: To standardize the requirements for medicines regulation throughout the world
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INTERNATIONAL CONFERENCE ON HARMONISATION (ICH) GUIDELINES
Members
ICH is comprised of representatives from six parties that represent the regulatory bodies and
research-based industry in the European Union, Japan and the USA.
• Japan
Ministry of Health, Labour and Welfare (MHLW)
Japan Pharmaceutical Manufacturers Association (JPMA)
• Europe
European Union (EU)
European Federation of Pharmaceutical Industries and Associations (EFPIA)
• USA
Food and Drug Administration (FDA)
Pharmaceutical Research and Manufacturers of America (PhRMA).
Additional members include Observers from the World Health Organization (WHO), European
Free Trade Association (EFTA), and Canada. The Observers represent non-ICH countries and
regions.
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ERRORS IN ANALYTICAL
CHEMISTRY
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ERRORS IN ANALYTICAL CHEMISTRY
GROSS ERROR
RANDOM ERROR
S Y S T E M AT I C E R R O R
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GROSS ERROR
• Involves a major breakdown in the analytical process
• Often the product of human error
• Or personal bias
EXAMPLES
1. Samples being spilt
2. Wrong dilutions being prepared
3. Instruments breaking down
4. Instruments being used in the wrong way
If a gross error occurs, the results are rejected and the analysis is repeated from the
beginning.
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RANDOM ERROR
S Y S T E M AT I C E R R O R
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EXAMPLE
A batch of paracetamol tablets are stated to contain 500 mg of paracetamol per tablet. For the
purpose of this example it is presumed that 100% of the stated content is the correct answer.
Four students carry out a spectrophotometric analysis of a sample from the tablets and
obtained the following percentages of stated content for the repeat analysis of paracetamol in
the tablets:
T1 T2 T3 T4 T5 ഥ
𝒙 𝒔
Student 1 99.5 % 99.9 % 100.2 % 99.4 % 100.5 %
Student 2 95.6 % 96.1 % 95.2 % 95.1 % 96.1 %
Student 3 93.5 % 98.3 % 92.5 % 102.5 % 97.6 %
Student 4 94.4 % 100.2 % 104.5 % 97.4 % 102.1 %
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EXAMPLE
T1 T2 T3 T4 T5 ഥ
𝒙 𝒔
Student 1 99.5 % 99.9 % 100.2 % 99.4 % 100.5 %
Student 2 95.6 % 96.1 % 95.2 % 95.1 % 96.1 %
Student 3 93.5 % 98.3 % 92.5 % 102.5 % 97.6 %
Student 4 94.4 % 100.2 % 104.5 % 97.4 % 102.1 %
𝑛 σ(𝑥𝑖 −𝑥)ҧ2
σ𝑖=1 𝑥𝑖 𝑠=
𝑥ҧ = (𝑛 − 1)
𝑛
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EXAMPLE
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EXAMPLE
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RANDOM ERROR SYSTEMATIC ERROR

• Indeterminate • Determinate
• Affects precision • Affects accuracy
• Small differences in measurements • Has definite value or assignable cause
• Difficult to eliminate • Can be eliminated
• Quantifiable through standard deviation • Quantifiable by difference between
mean and true value
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T Y P E S O F S Y S T E M AT I C E R R O R
1. Instrumental Error
• Caused by imperfections in measuring devices
• Use of wrong grade of chemicals
2. Methodological Error
• Due to nonideal chemical or physical behavior of the reagents and reactions
3. Personal/Operative Error
• Arise from prejudice or natural tendency to estimate scale readings
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TITRIMETRIC ANALYSIS
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o r V O LU M E T R I C A N A LY S I S
• Involves a solution of reagent of known concentration (titrant) added to a solution of analyte
until reaction is judged complete (endpoint)
• The determination of the volume of a solution of known concentration required to react

with a given amount of the substance to be analyzed
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o r V O LU M E T R I C A N A LY S I S
TITRATION
An analytical method in which the volume of a solution of known concentration consumed
during an analysis is taken as a measure of the amount of active constituent in a sample
analyzed
HCl + NaOH → NaCl + H2O
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C L A S S I F I C AT I O N U S E D F O R O F F I C I A L A S S AY S
1. Titrimetry
2. Gravimetry
3. Spectrometry
4. Chromatography
5. Electrometric
6. Miscellaneous
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DEFINITION OF TERMS
ANALYTE
• Active constituent in the sample
• Titrand, sample
• Unknown concentration
TITRANT
• Standard solution, volumetric solution
• Known concentration
INDICATOR
• Chemicals capable of changing colors when end point is reached in which equivalent
quantities of analyte and titrant have been reached
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DEFINITION OF TERMS
EQUIVALENCE POINT
• Theoretical or stoichiometric endpoint
• Point at which a chemically equivalent amount of titrant has reacted with the analyte
END POINT
• Practical
• Point at which the reaction is observed to be complete
• A sudden change apparent by use of indicators
TITRATION ERROR
• Equivalence point – End point
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REVIEW: CONCENTRATION
• Concentration is a general term expressing the amount of solute contained in a given

amount of material
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MOLARITY
• The number of moles of solute divided by the number of liters of solution containing the
solute
• One can also express the amount in millimoles and the volume in milliliters
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑚𝑜𝑙𝑒𝑠) 𝑎𝑚𝑜𝑢𝑛𝑡 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑚𝑖𝑙𝑙𝑖𝑚𝑜𝑙𝑒𝑠)
𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 = =
𝑣𝑜𝑙𝑢𝑚𝑒 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 (𝑙𝑖𝑡𝑒𝑟𝑠) 𝑣𝑜𝑙𝑢𝑚𝑒 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 (𝑚𝑖𝑙𝑙𝑖𝑙𝑖𝑡𝑒𝑟𝑠)
RECALL: the number of moles of a substance is related to its weight in grams through the
molecular weight (MW), the amount of a substance in moles describes the number of particles
or molecules present
𝑤𝑒𝑖𝑔ℎ𝑡 (𝑔𝑟𝑎𝑚𝑠) 𝑤𝑒𝑖𝑔ℎ𝑡 (𝑚𝑖𝑙𝑙𝑖𝑔𝑟𝑎𝑚𝑠)

𝑎𝑚𝑜𝑢𝑛𝑡 𝑚𝑜𝑙𝑒𝑠 = 𝑎𝑚𝑜𝑢𝑛𝑡 𝑚𝑖𝑙𝑙𝑖𝑚𝑜𝑙𝑒𝑠 =
𝑀𝑊 𝑀𝑊
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What is the molarity of sodium hydroxide solution prepared by dissolving 2.40 g of NaOH and
diluting to 500 mL with water?
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑚𝑜𝑙𝑒𝑠)
𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 =
𝑣𝑜𝑙𝑢𝑚𝑒 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 (𝑙𝑖𝑡𝑒𝑟𝑠)
where
500 𝑚𝐿 2.40 𝑔 𝑁𝑎𝑂𝐻
𝑣𝑜𝑙𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 = = 𝟎. 𝟓𝟎𝟎 𝑳 and 𝑎𝑚𝑜𝑢𝑛𝑡 𝑁𝑎𝑂𝐻 = = 𝟎. 𝟎𝟔𝟎𝟎 𝒎𝒐𝒍 𝑵𝒂𝑶𝑯
𝑔 𝑁𝑎𝑂𝐻
1000 𝑚𝐿/𝐿 40.0
𝑚𝑜𝑙 𝑁𝑎𝑂𝐻
Substitution yields
0.0600 𝑚𝑜𝑙 𝑁𝑎𝑂𝐻

𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 = = 0.120 𝑀
0.500 𝐿 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
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How many grams of potassium permanganate are needed to prepare 250 mL of a 0.100 M
solution?
𝑤𝑒𝑖𝑔ℎ𝑡𝐾𝑀𝑛𝑂4 (𝑔) = 𝑎𝑚𝑜𝑢𝑛𝑡𝐾𝑀𝑛4 (𝑚𝑜𝑙) × 𝑀𝑊𝐾𝑀𝑛𝑂4
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑚𝑜𝑙𝑒𝑠)

𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 =
𝑣𝑜𝑙𝑢𝑚𝑒 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 (𝑙𝑖𝑡𝑒𝑟𝑠)
𝑚𝑜𝑙
𝑎𝑚𝑜𝑢𝑛𝑡𝐾𝑀𝑛𝑂4 = 0.100 × 0.250𝐿 = 𝟎. 𝟎𝟐𝟓𝟎 𝒎𝒐𝒍
𝐿
𝑔 𝐾𝑀𝑛𝑂4
𝑤𝑒𝑖𝑔ℎ𝑡𝐾𝑀𝑛𝑂4 𝑔 = 0.0250 𝑚𝑜𝑙 𝐾𝑀𝑛𝑂4 × 158 = 𝟑. 𝟗𝟓 𝒈
𝑚𝑜𝑙 𝐾𝑀𝑛𝑂4
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DEFINITION OF TERMS
MOLARITY
𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒
𝑀 𝑀𝑜𝑙𝑎𝑟𝑖𝑡𝑦 =
𝑙𝑖𝑡𝑒𝑟𝑠 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
NORMALITY
𝑁 𝑁𝑜𝑟𝑚𝑎𝑙𝑖𝑡𝑦 = 𝑓 × 𝑀
MOLALITY
𝑚𝑜𝑙𝑒𝑠 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒
𝑚 𝑀𝑜𝑙𝑎𝑙𝑖𝑡𝑦 =
𝑘𝑔 𝑜𝑓 𝑠𝑜𝑙𝑣𝑒𝑛𝑡
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DEFINITION OF TERMS
REPLACEABLE HYDROGEN
ACIDS # of replaceable Hydrogen
1 HCl
2 H2SO4
1 CH3COOH
BASES # of replaceable OH
1 NaOH
2 Mg(OH)2
3 Al(OH)3
SALTS total positive or negative charges/ cation or anion

1 NaCl
2 MgO
6 Ca3(PO4)2
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DEFINITION OF TERMS
EQUIVALENT
• 1 equivalent of an acid neutralizes exactly 1 equivalent of a base, and vice versa
• 1 equivalent of an oxidizing agent reacts with exactly 1 equivalent of a reducing agent, and
vice versa
• Quantity of a substance that is chemically equivalent to 1.0079 g of hydrogen or hydrogen

ions
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DEFINITION OF TERMS
EQUIVALENT
Examples
• 1 mole or 36.46 g of HCl and and 0.5 mol or 49.035 g of H2SO4 contains 1.0079 g of hydrogen
ions (1 equiv) and is capable of neutralizing exactly 1 mol (1 equiv) or 40.00 g of NaOH or 0.5
mol or 85.675 g of Ba(OH)2
• 0.25 mol or 7.997 g of oxygen gains electrons equivalent to those gained by 1.0079 g of
hydrogen ions when they act as an oxidizing agent and 1 mol or 166.00 g of KI loses electrons
equivalent to those lost by 1.0079 g of hydrogen when it acts as a reducing agent
• Number of gram-equivalents involved in a quantitative procedure
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DEFINITION OF TERMS
GRAM – EQUIVALENT WEIGHT (GEW)
• Weight in grams which is chemically equivalent to 1 gram-atom of hydrogen (1.0079 g)
• [Neutralization reactions] weight of a substance in grams which contains, furnishes, reacts

with directly or indirectly or replaces 1 gram-atom or ion of hydrogen
GRAM – MILLIEQUIVALENT WEIGHT (GmEW)

• GEW/1000
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DEFINITION OF TERMS
BLANK DETERMINATION
• Entire procedure is repeated except that the analyte is omitted
• Conduct for correction and to enhance reliability of end point
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DEFINITION OF TERMS
VOLUMETRIC SOLUTION
BASED ON METHOD OF PREPARATION
1. Primary Standard VS
• obtained from a substance which approaches 100% purity
• does not require standardization
• [0.05 M KIO3]
2. Secondary Standard VS
• not sufficiently pure and is standardized against a primary standard or previously
standardized volumetric solution
• [0.1 N NaOH VS, 0.1 N AgNO3]
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DEFINITION OF TERMS
STANDARDIZATION
• Process of determining the exact value of a volumetric solution
• Determining the exact concentration using known amount of Primary standard or Secondary
standard
TYPES OF STANDARDS
1. Primary Standard
• pure solid substitute used for direct standardization of a solution
2. Secondary Standard
• standard solution of known concentration, these are volumetric solutions
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DEFINITION OF TERMS
PRIMARY STANDARD
REQUIREMENTS FOR PRIMARY STANDARD
1. It must be available in a highly pure state.
2. It must be readily soluble in the desired solvent.
3. It must not suffer decomposition in the presence of the solvent.
4. It must be stable and unaffected by the atmosphere.
5. It should have a large equivalent weight so that weighing errors are minimum.
6. Its solution should not deteriorate on keeping.
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DEFINITION OF TERMS
PRIMARY STANDARD
1. Sodium Hydroxide
4 PRIMARY STANDARDS
Potassium acid phthalate (KHP) / C6H4COOK·COOH
Sulfamic acid (HSO3)
Benzoic aid
Potassium acid iodate
2. Hydrochloric Acid
Standardized using titrimetric methods using sodium carbonate of known purity as a
primary standard
Using standard NaOH as a secondary standard
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DEFINITION OF TERMS
PRIMARY STANDARD
VOLUMETRIC SOLUTION PRIMARY STANDARD INDICATOR

Sodium thiosulfate VS KIO3 / K2Cr2O7 /Starch
EDTA VS Zn metal/CaCO3 /Hydroxynaphthol
Sodium hydroxide KHP/HSO3 Phenolphthalein
Hydrochloric acid Na2CO3 Phenolphthalein
Silver nitrate NaCl K2CrO4
Potassium permanganate Na2C2O4
Iodine As2O3 Starch
Sodium methoxide Benzoic acid Thymol blue
Ceric sulfate As2O3 Starch
Karl Fischer Reagent Na2C4H4O6
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DEFINITION OF TERMS
SECONDARY STANDARD
• A solution of known concentration used to standardize another solution
VOLUMETRIC SOLUTION PRIMARY STANDARD INDICATOR
HCl NaOH Phenolphthalein
NH4SCN AgNO3 Ferric alum
Na2S2O3 Iodine Starch
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PRACTICE PROBLEM - #1
Calculate the normality of a NaCl solution prepared by dissolving 2.9216 g of NaCl in
H2O and adding more water make 500 mL of solution. (MW of NaCl = 58.44g/mole)
m o l NaCl
2.9216 𝑔
= 0.049993 𝑚𝑜𝑙
58.44 𝑔/𝑚𝑜𝑙
N solution
𝐹 × 𝑚𝑜𝑙𝑁𝑎𝐶𝑙 1 × 0.49993 𝑚𝑜𝑙
𝑁= = = 0.099986 N = 0.1 N
𝐿𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 0.5 𝐿
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Find the normality of 30 g NaOH diluted to a volume of 0.5L. (MW of NaOH= 40
g/mole)
N solution
𝑤𝑡𝑁𝑎𝐶𝑙 30 𝑔
𝐹 × 𝑚𝑜𝑙𝑁𝑎𝐶𝑙 𝐹× 1×
𝑀𝑊𝑁𝑎𝐶𝑙 40 𝑔/𝑚𝑜𝑙 0.75 𝑚𝑜𝑙
𝑁= = = = = 1.5 𝑁
𝐿𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝐿𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 0.5 𝐿 0.5 𝐿
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What is the normality of H2SO4 containing 73.5 g/500 mL of solution? (MW of H2SO4
= 98 g/mole)
N solution
𝑤𝑡𝑁𝑎𝐶𝑙 73.5 𝑔
𝐹 × 𝑚𝑜𝑙𝑁𝑎𝐶𝑙 𝐹× 2×
𝑀𝑊𝑁𝑎𝐶𝑙 98 𝑔/𝑚𝑜𝑙 2 × 0.75 𝑚𝑜𝑙
𝑁= = = = =3𝑁
𝐿𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝐿𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 0.5 𝐿 0.5 𝐿
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How many grams of NaOH pellets are needed to make 500 mL of 1.5 N solution?
(MW of NaOH = 40 g/mole)
N solution
𝑤𝑡𝑁𝑎𝐶𝑙
𝐹 × 𝑚𝑜𝑙𝑁𝑎𝐶𝑙 𝐹×
𝑀𝑊𝑁𝑎𝐶𝑙
𝑁= =
𝐿𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝐿𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
𝑤𝑡𝑁𝑎𝐶𝑙
1×
40 𝑔/𝑚𝑜𝑙
1.5 𝑁 =
0.5 𝐿
𝑤𝑡𝑠𝑜𝑙𝑢𝑡𝑒 = 30 𝑔
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Compute for normality of HCl that makes use of the primary standard Na2CO3
weighing 1.5 g. The Na2CO3 consumed 30 mL of HCl after titration. (MW of Na2CO3 =
106 g/mole)
𝑚𝑔𝑠𝑎𝑚𝑝𝑙𝑒 = 𝑁 × 𝑉 𝑚𝐿 × 𝑚𝐸𝑞
1500 𝑚𝑔 = 𝑁 × 30 𝑚𝐿 × 106 𝑚𝑔
𝑁 = 0.471698𝑁
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VOLUMETRIC APPARATUS
TYPES
to deliver to contain
BURETS VOLUMETRIC FLASK
PIPETS GRADUATED CYLINDERS
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BURET
• Graduated glass tubes of uniform bore throughout the
whole length
• Closed at the bottom by glass or stopcock
• Volumes read at lower meniscus except highly colored

liquid
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BURET
PRECAUTIONS FOR USE
• All burets should be tested for leakage before use.
• Glass stopcocks may require a small amount of special stopcock lubricant to prevent leakage
and permit ease of operation.
• Reading Burets: The surface of liquids in narrow tubes is always curved because of capillarity,
the surface or meniscus is always concave when the liquid wets the tube and convex when it
does not. Readings should always be made at the lowest point of the meniscus (the
graduation mark that coincides with the bottom of the curve, except when measuring highly
colored liquids. The eye must be on the same level as the meniscus, otherwise error due to
parallax will be introduced.
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BURET
M E T H O D S O F C A L I B R AT I O N
• Ostwald Pipet
• Kiehl Buret
TYPES OF BURET
MOHR GEISSLER
• Economical • More expensive
• With rubber tubing at the tip • For acids and bases
• For bases
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VOLUMETRIC FLASK
• Should be calibrated to contain the indicated volume when
filled to the mark
• Used to make up standard solutions
• *graduated to contain, and not to deliver the calibrated

volume
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GRADUATED CYLINDER
• Used in making approximate measures of volume
• Graduated to contain a given volume of liquid at standard

temperature
• The inside diameter of the cylinder should not exceed one-fifth of the
graduated length
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PIPET
• Should be graduated to deliver at
standard temperature the volume
indicated
• Should never be drained by blowing

into them unless they are especially
graduated for use in the way
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SOURCES OF ERROR IN THE USE OF VOLUMETRIC APPARATUS
Every precaution should be taken to avoid the following common sources of error in the use of
volumetric apparatus
1. Rinse water adhering to walls of apparatus

The apparatus may be dried, but it is more convenient and just as accurate to wash it out
with small successive portions of the liquid to be used, discarding the washings.
2. Grease films and dirty apparatus
Dirt and oil cause irregularity in the delivery of liquids and distort the meniscus
3. Parallax
Must be avoided to secure proper readings of the level of the meniscus
4. Variations in temperature
Lead to changes in volume of vessels and liquids, all measurements therefore should be
made at a temperature closely approximating that at which the apparatus was calibrated
5. Air bubbles trapped beneath liquid surface
Especially below the stopcock in burets, displace liquids
6. Heat
Hot solutions cause calibrated volumetric apparatus to suffer change in volumes
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CLEANING SOLUTION
• Volumetric apparatus should always be cleaned before using and in use should be cleaned as
often as necessary
• The adherence of droplets to the wall of a buret or pipet is positive evidence that the
apparatus is dirty
• In a clean instrument, the liquid drains down uniformly, wetting the walls so that no droplets
are observable
CLEANING AGENTS
*use warm cleaning solutions
a. Sodium dichromate in sulfuric acid
b. Solution of trisodium phosphate
c. Solution of synthetic detergent
Note: Hot solutions should be avoided when cleaning accurately calibrated apparatus, because
of the possible production of a permanent change in volume caused by the heat and known as
thermal aftereffect.
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59
ASSAY
The determination of the content of a specific component with no evaluation of other components
ANALYTE TYPE TITRANT INDICATOR
Acetic acid Alkalimetric-direct NaOH phpt
Milk of Magnesia Acidimetric- residual NaOH mr
Aspirin Alkalimetric-residual HCl phpt
NaCl Volhard-precipitation. NH4SCN FAS
Povidone-Iodine NH4SCN FAS
Calcium lactate Complexation EDTA hydroxynaphthol
H2 O 2 Redox-direct KMnO4
NaNO2 Redox- residual KMnO4
Ammonium Potassium tartrate Iodimetry Iodine starch
CuSO4 Iodometry Na2S2O3 starch
Menadione (Vit. K) Redox
Selenium Sulfide Iodometry
Phenol Iodometry- Residual
Malic Acid Indirect Permanganate
Oxidation
Sulfonamide Diazotization
NaHCO3 Direct Acidimetry
ZnO Acidimetry – Residual / EDTA –
Direct 60
CaCO3 EDTA - Direct 60
DEFINITION OF TERMS
TITER VALUE
• Expresses the equivalency of a standard solution with the amount of substance under assay
𝑚𝑔 𝑎𝑛𝑎𝑙𝑦𝑡𝑒
𝑡𝑖𝑡𝑒𝑟 𝑣𝑎𝑙𝑢𝑒 =
𝑚𝐿 𝑡𝑖𝑡𝑟𝑎𝑛𝑡
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61
TYPES OF TITRATION
1. Direct Titration
2. Indirect Titration
3. Residual Titration
62
62
ACIDIMETRIC ASSSAY – DIRECT TITRATION WITH ACID
SUBSTANCE INDICATOR
Aminophylline (USP) mo
Calcium hydroxide solution (USP) phen
Potassium Hydroxide (USP) phen
Pyrazinamide (USP) mo
Sodium bicarbonate (USP) mo
Ammonia spirit aromatic (NF) mo
Potassium bicarbonate (NF) mo
Tromethamine (NF) bcp
63
63
ACIDIMETRIC ASSSAY – RESIDUAL TITRATION OF EXCESS ACID WITH BASE
SUBSTANCE INDICATOR
Calamine (USP) mo
Lidocaine (USP) bcg/mr
Milk of magnesia (USP) mr
Magnesium oxide (USP) mo
Zinc Oxide (USP) mo
Ammonia solution, strong (NF) mr
Magnesium carbonate (NF) mo
Methenamine (NF) mr
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64
ALKALIMETRIC ASSSAY – DIRECT TITRATION WITH BASE
SUBSTANCE INDICATOR
Benzaldehyde (USP) bpb
Furosemide (USP) btb
Iopanoic acid tablets (USP) thb
Propylthiouracil (USP) btb
Salicylic acid (USP) phen
Boric acid (NF) phen
Niacin (NF) phen
Tartaric acid (NF) phen
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65
ALKALIMETRIC ASSSAY – RESIDUAL TITRATION OF EXCESS ACID WITH BASE
SUBSTANCE INDICATOR
Aspirin (USP) phen
Lactic acid (USP) phen
Methylparaben (USP) phen
Propylparaben (USP) btb
Alginic acid (NF) phen
Calcium phosphate, tribasic (NF) phen
Poldine methyl sulfate (NF) crr
Rubbing alcohol (NF) phen
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66
TYPES OF TITRATION
D I R E C T T I T R AT I O N
• Analyte is reacted with titrant after rendering it soluble in the titration medium
• Conducted by introducing a standard solution gradually from a buret into the analyte
• One titrant (VS) used
𝑀𝑊
𝑁 × 𝑉(𝑚𝐿) ×
𝑓 × 1000
%𝑃 = × 100
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒 (𝑔)
𝑁 × 𝑉 𝑚𝐿 × 𝑚𝑒𝑞 𝑤𝑡
%𝑃 = × 100
67
67
PRACTICE PROBLEM - #1 – Direct Titration
ASSAY OF SODIUM BICARBONATE
Weigh accurately about 3 g of sodium bicarbonate, mix with 25 mL of water, add
methyl orange TS, and titrate with 1 N sulfuric acid. Each milliliter of 1 N sulfuric acid
is equivalent to 84.01 mg of NaHCO3.
• It is a general rule that when the substance to be assayed is a solid, the accurately weighed quantity to
be used should be dissolved in sufficient water to make the solution of about the same equivalent
concentration as that of the acid to be used in the titration.
• Methyl orange is used as indicator because phenolphthalein and most other indicators are affected by
the carbonic acid liberated in the reaction, which causes a change in color before the reaction is
complete.
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68
𝟐𝑵𝒂𝑯𝑪𝑶𝟑 + 𝑯𝟐 𝑺𝑶𝟒 → 𝑵𝒂𝟐 𝑺𝑶𝟒 + 𝟐𝑯𝟐 𝑶 + 𝑪𝑶𝟐 ↑

2 (84.01)
• From the equation it is obvious that 2 mol of NaHCO3 is equivalent to 1 mol of H2SO4.
• Therefore 1 mol of NaHCO3 is 1 equiv, and the equivalent weight is equal to the gram molecular
weight, 84.01 g.
• One milliliter of 1 N sulfuric acid or 1 meq is equivalent to 84.01 mg or 1 meq of NaHCO3.
69
69
2 (84.01)
%𝑃 = × 100
If exactly 3.0 g of NaHCO3 is dissolved in 25 mL of water in the above assay, what will be the normality of
the solution? Does the normality conform to the general rule stated in the discussion?
70
70
2 (84.01)
%𝑃 = × 100
If a 0.2800 g sample of sodium bicarbonate (96.5% NaHCO3) is titrated with 0.9165 N sulfuric acid, what
volume of the acid should be required to produce the endpoint?
71
71
2 (84.01)
%𝑃 = × 100
Calculate the following titer values for 1 N sulfuric acid
a. KHCO3
b. K2CO3
c. CaCO3
72
72
TYPES OF TITRATION
I N D I R E C T T I T R AT I O N
• Analyte undergoes preliminary treatment prior to titration
73
73
TYPES OF TITRATION
R E S I D UA L T I T R AT I O N
• A measured excess of one VS is added which will react completely with the analyte
• The unreacted excess is then back titrated with another VS
• “back titration”
• Adding an accurately measured quantity of standard solution in excess and titrating the
excess with another standard solution
74
74
TYPES OF TITRATION
R E S I D UA L T I T R AT I O N
Two VS used
1st VS: added in excess
2nd VS: used to titrate the excess
Used when direct titration is not practicable

Compounds which react too slowly with titrant
Compound with poor water solubility
Volatile substance
Blank Determination: process of repeating the procedure but omitting the sample
𝑀𝑊 𝑀𝑊
(𝑁1 𝑉1 − 𝑁2 𝑉2 ) × 𝑁(𝑉𝑏 − 𝑉𝑎 ) ×
𝑓 × 1000 𝑓 × 1000
%𝑃 = × 100 %𝑃 = × 100
𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒 (𝑔) 𝑤𝑡 𝑠𝑎𝑚𝑝𝑙𝑒 (𝑔)
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75
TYPES OF REACTIONS IN TITRIMETRIC ANALYSIS
1. Neutralization (acid-base) in aqueous and nonaqueous solvents

2. Oxidation-Reduction
3. Precipitation
4. Complexation
REQUIREMENT FOR A REACTION TO BE USED FOR TITRIMETRIC ANALYSIS

1. The reaction must proceed to completion
Chemical equilibrium constant K must be equal to or greater than 108
2. The reaction must proceed in a stoichiometric manner
3. A suitable end point detecting device must be available
Chemical indicators, electrodes, etc
4. For direct titrimetric methods the reaction must be rapid so a sharp end point is discernible
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76
NEUTRALIZATION
REACTIONS
77
NEUTRALIZATION REACTIONS
NEUTRALIZATION
• Reaction of acid and based
NEUTRALIZATION REACTIONS
• Chemical processes in which an acid (proton donor) reacts with a base (proton acceptor)
• The products of a neutralization reaction in aqueous solution are water and a salt (NaCl,
sodium acetate, NH4Cl, etc, depending on the acid and base used in the reaction)
78
78
REVIEW OF CONCEPTS
1.pH
2.Buffer Capacity
3.Salt Formation
79
79
pH
• Power of hydrogen ion H+
• Number of gram equivalent of OH- in a liter of solution
• pH = - log[H+]
THEORY ACID BASE
ARRHENIUS yields H+ yields OH-
LEWIS e- acceptor e- donor
BRONSTED-LOWRY proton donor proton acceptor
CLASSIFICATION BASED ON pH
Strong acid: pH < 3
Strong base: pH > 11
Weak acid: pH 4-6
Weak base: pH 8-10
80
80
pH
H E N D E R S O N – H A S S E L B A L C H E Q UAT I O N
FOR WEAK ACIDS

[𝑠𝑎𝑙𝑡]
𝑝𝐻 = 𝑝𝐾𝑎 + log
[𝑎𝑐𝑖𝑑]
FOR WEAK BASES
[𝑏𝑎𝑠𝑒]
𝑝𝐻 = 𝑝𝐾𝑎 + log
[𝑠𝑎𝑙𝑡]
𝑝𝐾𝑎 + 𝑝𝐾𝑏 = 14
81
81
Calculate the pH of solution which contains 3.7 x 10-2 moles of NH4Cl and 4.8 x 10-2
moles of ammonia (pKb = 4.74) in 1 L of solution.
82
82
A buffer solution contains 0.1 M each of acetic acid and sodium acetate. The acid
dissociation of acetic acid at 25 °C is 1.8 x 10-3. What is the pH of the solution?
83
83
TITRATION CURVE
The manner in which the pH of a solution changes during a titration is best shown by preparing
a graph in which the pH value is plotted on the y-axis and the volume of the titrant is plotted on
the x-axis.
• Equivalence point on the titration curve is that portion where the slope of the curve is
steepest and is commonly referred to as the break in the titration curve.
• When an indicator is used to detect the equivalence point, it must give a sharp discernible
color change at that point in the titration; otherwise the color change may lead to erroneous
results.
• Titration curves can show which indicator is suitable for a given titration.
84
TITRATION CURVE
85
TITRATION CURVE
The preparation of a titration curve is not difficult if one realizes that the calculations are based
on only four types of points, which correspond to:
1. The pH of the solution being titrated but before any titrant is added (pH1)
2. The pH of the solution after titrant is added but before the equivalence point is reached
(pH2)
3. The pH at the equivalence point (pH3)
4. The pH beyond the equivalence point (pH4)
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86
TITRATION CURVE
T I T R AT I O N O F A S T R O N G A C I D U S I N G A S T R O N G B A S E
Suppose that 20.00 mL of exactly 0.1 N HCl were taken, diluted with sufficient distilled water to
measure exactly 100 mL, and titrated with exactly 0.1 N NaOH.
pH1: Calculate the pH of the solution before any titrant is added

20.00 𝑚𝐿 × 0.1 𝑁 = 2.00 𝑚𝑒𝑞 𝑜𝑓 𝐻𝐶𝑙 𝑖𝑛 100 𝑚𝐿 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛
2.00 𝑚𝑒𝑞
𝐻3 𝑂+ = = 2.00 × 10−2 𝑁
100 𝑚𝐿
𝑝𝐻 = − log 2.00 × 10−2 = 𝟏. 𝟕𝟎
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87
TITRATION CURVE
pH2: Calculate the pH of the solution after 15.00 mL of 0.1 N NaOH is added
20.00 𝑚𝐿 × 0.1 𝑁𝐻𝐶𝑙 = 2.00 𝑚𝑒𝑞 𝑜𝑓 𝐻𝐶𝑙 𝑜𝑟𝑖𝑔𝑖𝑛𝑎𝑙𝑙𝑦 𝑝𝑟𝑒𝑠𝑒𝑛𝑡
15.00 𝑚𝐿 × 0.1 𝑁𝑁𝑎𝑂𝐻 = 1.50 𝑚𝑒𝑞 𝑜𝑓 𝑁𝑎𝑂𝐻 𝑎𝑑𝑑𝑒𝑑
2.00 − 1.50 = 0.50 𝑚𝑒𝑞 𝑜𝑓 𝐻𝐶𝑙 𝑟𝑒𝑚𝑎𝑖𝑛𝑠
+
0.50 𝑚𝑒𝑞 −3
𝐻3 𝑂 = = 4.35 × 10 𝑁
(100 + 15) 𝑚𝐿
−3
𝑝𝐻 = − log 4.35 × 10 = 𝟐. 𝟑𝟔
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TITRATION CURVE
2.00 − 2.00 = 0.00 𝑚𝑒𝑞 𝑜𝑓 𝐻𝐶𝑙 𝑟𝑒𝑚𝑎𝑖𝑛𝑠
𝑝𝐻 = 𝟕. 𝟎𝟎
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TITRATION CURVE
2.90 − 2.00 = 0.90 𝑚𝑒𝑞 𝑜𝑓 𝑁𝑎𝑂𝐻 𝑟𝑒𝑚𝑎𝑖𝑛𝑠
0.90
𝑂𝐻− = = 6.98 × 10−3 𝑁
100 + 29 𝑚𝐿
𝑝𝑂𝐻 = − log 6.98 × 10−3 = 2.16

𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝑂𝐻 = 14.00 − 2.16 = 𝟏𝟏. 𝟖𝟒
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90
TITRATION CURVE
As can be seen in the curve, either phenolphthalein or methyl red indicators are
suitable.
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SALT FORMATION
1. Strong Acid + Strong Base = ? – HCl+ NaOH.________
• 2. Strong Acid + Weak Base = ? – HCl + NH3.________
• 3. Strong Base + Weak Acid = ? – NaOH+ CH3COOH ._______
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CLASSIFICATION
BASED ON MEDIA USED
1. Aqueous Medium
2. Non – aqueous Medium
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CLASSIFICATION
BASED ON TITRANT USED
1. Aqueous Medium
2. Non – aqueous Medium
ACIDIMETRY ALKALIMETRY
TITRANT acid base
ANALYTE base acid
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INDICATOR
Are complex organic compounds used to:
• Determine endpoint
• Determine the pH
• Indicate that a desired change in pH has been affected
CHARACTERISTICS
• Organic substances
• May be acids or bases themselves
• Capable of existing in two forms of different color that are mutually convertible, one into the
other at given hydrogen-ion concentrations
• Most of the indicators for acid-base titration are acidic
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INDICATOR
96
96
VISUAL END POINTS
• The end points of titrations are most often determined by noting some visual change in the
solution, usually color.
• These changes are always based on the fact that pA or pT changes dramatically and rapidly in
the vicinity of the equivalence point.
• There are three ways that color changes can occur near the equivalence point of a titration.
Regardless of its mechanism, the substance undergoing the color change is called an
indicator.
1. Colored titrants or analytes
2. Specific compound formers
3. Nonspecific, equilibrium-dependent compounds
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VISUAL END POINTS
Nonspecific, equilibrium-dependent compounds
Indicators of this types are characterized by two fundamental properties
a. they exist in two equilibrium forms (i.e. protonated-unprotonated or oxidized-reduced)
b. each form has a different color
The position of the equilibrium between the two forms of the indicator, and therefore its color,
depends in some way on the concentration of analyte or titrant in the solution.
The large relative and rapid change in analyte or titrant concentrations in the vicinity of the
equivalence point causes a large shift in the position of the indicator equilibrium.
When the concentrations of the two forms of the indicator change in order to coincide with the
new equilibrium, the observed color also changes.
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VISUAL END POINTS
The illustration shows the relationship between pH and the indicator color. The ladder diagram
defines pH values where each of the two forms of the indicator exist.
• The weak acid form, HIn, which in this example is

yellow
-
• The weak base form, In , which in this example is red
are the predominant species.
The indicator changes color when the pH is between

pKa – 1 and pKa – 1, changing from yellow to orange to
red (or from red to orange to yellow).
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99
VISUAL END POINTS
METHYL RED in its (a) weak acid, HIn, form, (c) its weak base, In–, form, and (b) a mixture of HIn
and In–. 100
100
VISUAL END POINTS
The relatively broad range of pH levels over which an indicator changes color means that using a visual indicator to locate the titration’s end point is subject to uncertainty. To minimize a determinate titration error,
an indicator’s entire pH range must fall within the rapid change in pH that occurs near the titration’s equivalence point. As shown in the figure below, phenolphthalein is an appropriate indicator for the titration of
50.0 mL of 0.050 M acetic acid with 0.10 M NaOH. Bromothymol blue, on the other hand, is an inappropriate indicator because its change in color begins before the initial sharp rise in pH, and, as a result, spans a
relatively large range of volumes. The early change in color increases the probability of obtaining inaccurate results, while the range of possible end point volumes increases the probability of obtaining imprecise 101
results. 101
INDICATOR
COLOR CHANGE
INDICATOR PH RANGE ACID BASE
Malachite green 0.0 – 2.0 Yellow Green
Methyl yellow 2.9 – 4.0 Red Yellow
Bromophenol blue 3.0 – 4.6 Yellow Blue
Methyl orange 3.2 – 4.4 Pink Yellow
Bromocresol green 4.0 – 5.4 Yellow Blue
Methyl red 4.2 – 6.2 Red Yellow
Bromocresol purple 5.2 – 6.8 Yellow Purple
Bromothymol blue 6.0 – 7.6 Yellow Blue
Phenol red 6.8 – 8.2 Yellow Red
Cresol red 7.2 – 8.8 Yellow Red
Thymol blue 8.0 – 9.2 Yellow Blue
Phenolphthalein 8.0 – 10.0 Colorless Red
Thymolphthalein 9.3 – 10.5 Colorless Blue
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INDICATOR
Are complex organic compounds used to:
• Determine endpoint
• Determine the pH
• Indicate that a desired change in pH has been affected
CHARACTERISTICS
• Organic substances
• May be acids or bases themselves
• Capable of existing in two forms of different color that are mutually convertible, one into the
other at given hydrogen-ion concentrations
• Most of the indicators for acid-base titration are acidic
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103
PHENOLPHTHALEIN
• Approximate pH range for color change: 8.0 – 9.8
• [clear] [red violet]
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104
METHYL RED
• Approximate pH range for color change: 4.4 – 6.2
• [red] [yellow]
105
105
INDICATOR
1. Aqueous Medium
a. SA + SB
b. WA + SB
c. WB + SA
d. WB + WA
2. Non-aqueous Medium
a. WB + salt
b. Relatively SB
c. Strong acid
d. Weak acid
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INDICATOR
AQUEOUS MEDIUM
SA + SB 1. Phenolphthalein
2. Methyl orange
3. Methyl red
WA + SB 1. Phenolphthalein
WB + SA 1. Methyl red
WB + WA Not possible
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INDICATOR
NON AQUEOUS MEDIUM
WB + salt 1. Crystal violet
2. Methylrosanilinechloride
3. Quinidine
4. Malachite green
Relatively SB 1. Methyl red
2. Methyl orange
3. Strong acid
4. Thymol blue
WA 1. Azoviolet
2. O-nitroaniline
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108
INDICATOR
AZO DYES
ACID COLOR BASE COLOR
Methyl yellow Red Yellow
Methyl orange Pink Yellow
Methyl red Red Yellow
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109
INDICATOR
SULFONPHTHALEINS
Bromophenol blue Yellow Blue
Bromothymol blue Yellow Blue
Bromocresol green Yellow Blue
Bromocresol purple Yellow Purple
Malachite green Yellow Green
Phenol red Yellow Red
Cresol red Yellow Red
Thymol blue Yellow Blue
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110
INDICATOR
PHTHALEINS
Phenolphthalein Colorless Pink
Thymolphthalein Colorless Blue
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111
RULE FOR THE USE OF INDICATORS
1. Use 3 drops of indicator test solution for a titration unless otherwise directed.
2. When a SA is titrated with a SB, or a SB with a SA, methyl orange, methyl red or
phenolphthalein may be used.
3. When a WA is titrated with a SB, use phenolphthalein as the indicator.
4. When a WB is titrated with a SA, use methyl red as the indicator.
5. A WB should never be titrated with a WA, or vice versa, since no indicator will give a sharp
end point.
6. The appearance of a color is more easily observable than is the disappearance. Therefore,
always titrate where possible to the appearance of color.
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REVIEW
1. SA: HCl, HNO3, H2SO4, HI
2. SB: NaOH, KOH
3. WA: acetic acid, oxalic acid
4. WB: NH3
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113
ACIDIMETRY AND
ALKALIMETRY
114
ACIDIMETRIC ANALYSIS
ALKALIMETRIC ANALYSIS
1. • the direct or residual titrimetric analysis of ACIDS

2. • Direct: sample is acid, titrant is base
3. • Residual: sample is acid, treated with excess standard base, titrated with acid
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T Y P E S O F A C I D I M E T R I C A N A LY S I S
DIRECT TITRATION
• Standard acid solution from a buret into a solution of base being assayed
RESIDUAL TITRATION
• First volumetric solution (acid) is added in excess and the excess acid is titrated with standard
base
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EXAMPLES
ORGANIC SUBSTANCES
urea, sodium salicylate, diphenhydramine, emetine hydrochloride, meprobamate,
paramethadione, pyrazinamide
INORGANIC SUBSTANCES
sodium bicarbonate, milk of magnesia, ammonium chloride, calcium hydroxide, lithium
carbonate, zinc oxide
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117
P R A C T I C E P R O B L E M - # 1 A S S AY O F S O D I U M B I C A R B O N AT E
What is the purity of NaHCO3 if 0.29 g sample is titrated with 0.9289 N H2SO4. It
consumed 3.6 mL to reach the endpoint. (MW of NaHCO3 = 84 g/mole)
%𝑃 = × 100
118
118
If 0.28 g sample of NaHCO3 (96.5%) is titrated with 0.9165 N H2SO4 what volume of
the acid should be required to produce an endpoint?
%𝑃 = × 100
119
119
The disodium salt of a dibasic organic substance has a molecular weight of 215
g/mol, what weight of a sample would be used for titration to bromophenol blue
with 0.25 N acid in order that 35 mL of the latter will be required?
%𝑃 = × 100
120
120
Twenty sodium salicylate tablets labeled 325 mg were dispersed in sufficient water
to make 200 mL. A 15 mL aliquot of the filtrate was titrated to endpoint in the usual
way by 29.11 mL of 0.1000 N HCl. Calculate the amount in % of sodium salicylate.
(MW of Na salicylate = 160)
%𝑃 = × 100
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121
C O M P U TAT I O N – R E S I D UA L T I T R AT I O N
If a sample of magnesia magma weighing 5.2430 g when dissolved in 25 mL of
0.9915 N H2SO4 required 9.85 mL of 1.1402 N NaOH to titrate excess acid, what is the
percent of Mg(OH)2 present in the sample? –Mg = 24.31 –O = 16 –H = 1
𝑀𝑊
(𝑁1 𝑉1 − 𝑁2 𝑉2 ) ×
𝑓 × 1000
%𝑃 = × 100
122
122
If the USP requirement for magnesia magma is not less than 7% and not more than
8.5% Mg(OH)2 , did the sample conform to the official requirement?
𝑀𝑊
(𝑁1 𝑉1 − 𝑁2 𝑉2 ) ×
𝑓 × 1000
%𝑃 = × 100
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123
P R A C T I C E P R O B L E M - # 1 A S S AY O F M A G N E S I U M H Y D R OX I D E
Calculate the Mg(OH)2 content of milk of magnesia, 12.32 g of which was dissolved in
50 mL of 1.0340 N H2SO4, producing a mixture that required 24.6 mL of 1.1255 N
NaOH? (MWMg = 24.31; O=16; H=1)
𝑀𝑊
(𝑁1 𝑉1 − 𝑁2 𝑉2 ) ×
𝑓 × 1000
%𝑃 = × 100
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124
P R A C T I C E P R O B L E M - # 2 Z I N C OX I D E
If a 1.25 g sample of ZnO, were treated with 50 mL of 1.1230 N H2SO4 and required
27.5 mL of 0.9765N NaOH in the back titration. Compute % purity of ZnO. MW of
ZnO= 81.41
𝑀𝑊
(𝑁1 𝑉1 − 𝑁2 𝑉2 ) ×
𝑓 × 1000
%𝑃 = × 100
125
125
• the direct or residual titrimetric analysis of ACIDS
• Direct: sample is acid, titrant is base
• Residual: sample is acid, treated with excess standard base, titrated with acid
126
126
T Y P E S O F A L K A L I M E T R I C A N A LY S I S
DIRECT
sample is acid, titrant is base
RESIDUAL
sample is acid, treated with excess standard base, titrated with acid
127
127
P R A C T I C E P R O B L E M - # 1 D I R E C T T I T R AT I O N
A 5 mL of HCl, (SpGr= 1.3), required 50 mL of 1 N NaOH in a titration. Calculate the %
w/w HCl. (MW= 36.45)
128
128
P R A C T I C E P R O B L E M - # 2 D I R E C T T I T R AT I O N
Concentrated HCl (36.46 g/mol) has a purity of 36.5 % w/w (SpGr =1.18),
approximately how many mL of conc. HCl is needed to prepare 500 mL of 0.2 N
solution?
129
129
NITROGEN DETERMINATION BY KJELDAHL METHOD
• For organic compounds containing nitrogen
• Digest sample with concentrated H2SO4 until decomposition is complete
• NH3 is treated with excess H2SO4 with NaOH
130
130
NITROGEN DETERMINATION BY KJELDAHL METHOD
2 TYPES
1. METHOD 1 (MACRO)
2. METHOD 11 (SEMI MICRO)
The following hasten the digestion of ammonia with sulfuric acid:

1. potassium sulfate
2. Selenium
3. copper sulfate
131
131
PRACTICE PROBLEM - #1 KJELDAHL METHOD
The Kjeldahl procedure was used to analyze 5 g of organic acid. It was distilled into
50 mL of 0.055 N HCl and the mixture was titrated with 20 mL of 0.1010 N NaOH.
Calculate the %N in the sample (at. wt of N= 14)
132
132
NON AQUEOUS TITRATION
ACIDIMETRY
SOLVENTS
Acetonitrile Alcohol
Dioxane Benzene
Chloroform
TITRANT USED
Perchloric acid in glacial acetic acid or dioxane
Hydrogen bromide
INDICATORS
Crystal violet Quinaldine red
Naphtholbenzein Malachite green
Methyl red Methyl orange
Thymol blue
133
133
NON AQUEOUS TITRATION
ALKALIMETRY
SOLVENTS
Ethylenediamine N-butylamine
Morpholine
TITRANT USED
Sodium methoxide Lithium methoxide
Potassium methoxide Tetrabutyl ammonium hydroxide
INDICATORS
Crystal violet Quinaldine red
Naphtholbenzein Malachite green
Methyl red Methyl orange
Thymol blue Nitroaniline
hydroxyazobenzene
134
134
END.
135

PharmAnal 2

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PharmAnal 2

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Lecture 2

• Total amount of a group or class of compounds

PROXIMATE ANALYSIS • Deadly nightshade (belladona): alkaloid

• Peppermint: volatile oil

ULTIMATE ANALYSIS • Deadly nightshade (belladona): atropine

ULTRA MICRO < 1 mg

CHEMICAL Use reagents

RANDOM ERROR SYSTEMATIC ERROR

• The determination of the volume of a solution of known concentration required to react

HCl + NaOH → NaCl + H2O

• Concentration is a general term expressing the amount of solute contained in a given

𝑤𝑒𝑖𝑔ℎ𝑡 (𝑔𝑟𝑎𝑚𝑠) 𝑤𝑒𝑖𝑔ℎ𝑡 (𝑚𝑖𝑙𝑙𝑖𝑔𝑟𝑎𝑚𝑠)

0.0600 𝑚𝑜𝑙 𝑁𝑎𝑂𝐻

𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑠𝑜𝑙𝑢𝑡𝑒 (𝑚𝑜𝑙𝑒𝑠)

SALTS total positive or negative charges/ cation or anion

• Quantity of a substance that is chemically equivalent to 1.0079 g of hydrogen or hydrogen

• Number of gram-equivalents involved in a quantitative procedure

• [Neutralization reactions] weight of a substance in grams which contains, furnishes, reacts

GRAM – MILLIEQUIVALENT WEIGHT (GmEW)

• Conduct for correction and to enhance reliability of end point

VOLUMETRIC SOLUTION PRIMARY STANDARD INDICATOR

PIPETS GRADUATED CYLINDERS

• Closed at the bottom by glass or stopcock

• Volumes read at lower meniscus except highly colored

• Used to make up standard solutions

• *graduated to contain, and not to deliver the calibrated

• Graduated to contain a given volume of liquid at standard

• Should never be drained by blowing

1. Rinse water adhering to walls of apparatus

𝟐𝑵𝒂𝑯𝑪𝑶𝟑 + 𝑯𝟐 𝑺𝑶𝟒 → 𝑵𝒂𝟐 𝑺𝑶𝟒 + 𝟐𝑯𝟐 𝑶 + 𝑪𝑶𝟐 ↑

Used when direct titration is not practicable

1. Neutralization (acid-base) in aqueous and nonaqueous solvents

REQUIREMENT FOR A REACTION TO BE USED FOR TITRIMETRIC ANALYSIS

FOR WEAK ACIDS

pH1: Calculate the pH of the solution before any titrant is added

𝑝𝐻 = − log 2.00 × 10−2 = 𝟏. 𝟕𝟎

2.00 − 1.50 = 0.50 𝑚𝑒𝑞 𝑜𝑓 𝐻𝐶𝑙 𝑟𝑒𝑚𝑎𝑖𝑛𝑠

2.00 − 2.00 = 0.00 𝑚𝑒𝑞 𝑜𝑓 𝐻𝐶𝑙 𝑟𝑒𝑚𝑎𝑖𝑛𝑠

2.90 − 2.00 = 0.90 𝑚𝑒𝑞 𝑜𝑓 𝑁𝑎𝑂𝐻 𝑟𝑒𝑚𝑎𝑖𝑛𝑠

𝑝𝑂𝐻 = − log 6.98 × 10−3 = 2.16

• The weak acid form, HIn, which in this example is

are the predominant species.

The indicator changes color when the pH is between

1. • the direct or residual titrimetric analysis of ACIDS

The following hasten the digestion of ammonia with sulfuric acid:

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