Titration

of
Acid Base

1
 I. Concept of Acid Base
Concept Acid Base Neutralisation

Arrhenius Release H+ in Release OH- H+ + OH-

water in water H2O

Brönsted Donor H+ Acceptor Transfer proton

Lowry (proton) (acceptor) H+

Lewis Acceptor Donor couple Covalen

couple of of electron coordination
electron bonding

2
 Strong Acid
• Perfectly dissociated 100% to ions
• Mineral acid :
- Hydrochloric acid
- Perchloric Acid
- Sulfuric acid
- Nitric acid
- Acidtrichloroacetate
- pH = - log [Ca]

3
 Weak Acid
• Unperfectly dissociated acid
• Still detected species
• Mostly organic acid
• Concentration:

[H+] = √ Ka. Ca

pH = ½ (pKa-log Ca)

4
 Strong Base
• Perfectly dissociated
• NaOH and KOH
• [OH-] = Cb
• [OH-] = Kw/[H+]
• [H+] = Kw/ [OH-]
• pH = pKw-pOH

5
 Weak Base
• Not perfectly dissociated
• Amine, N- heterocyclic and hydrazine

[OH-] = √ Kb. Cb

pOH = ½ (pKb-log Cb)

6
• Based on Acidity and Basidity
character (Brönsted theory)

üProtogenic
üProtofilic
üAmphiprotic
üAprotic
 for making
Weak base becomes strong base
use solvent strong acid
for making
weak acid becomes strong acid

use solvent strong base

 Rule for non aqueous titration

• Solute must soluble

in solvent or
excess of titrant

• Product titration must soluble

in solvent

• solvent not resulting side reaction

Titration must free of water

solvent and reagent must free

of water
By adding anhidrida acetic

Apparatus must dry

 INDICATOR

Titrant
Aliquot

Terminologi
Titration Equivalent point ?
End point
?
 Titration Diagram
• Direct Titration

• Direct Titration with blank

Sample mek Sample

A B

Blank B
 • Back Titration
C other titrant will
Titrate excess A
Excess A

• Back Titration with blank

Sample Excess A
Back Titration
Excess A B C
Blank Titration
B D
blanko
 Calculation of Titration
• milieq titrant = milieq analyte

milieq analit = Vt.Nt

Vs.Ns = Vt. Nt

Vt.Nt = Weight of Sample (mg)

MW
 ACID BASE TITRATION
Each group will obtain samples (powder) of three substances
: acetylsalicylate, mefenamic acid, carbonate

REMEMBER :
- Perform a blank test (without sample, just water)
- When doing a titration à duplo or triplo
- Standardize your reagent! Especially the titrant
 EXERCISE

As a pharmacist in laboratory, you have been asked to determine amount

of acetosal/tablet. Calculate standardization

1). Standardization NaOH

2.075 g primary standard K Biftalat (MW 204,2) was titrated with indicator
fenolftalein and needs 10.5 dan 10.4 dan 10.6 ml NaOH.
2). Standardization HCl
10 ml HCl as titrated with NaOH 0.05 N and needs 9.8; 9.9 dan 9.7 ml
NaOH
3) A bottle of concentrated HCl (MW 36.5) was labelled as 37% (w/w);
density 1.19. Calculate Molarity of HCl!
 ACID BASE TITRATION
• Begin with the assumption of 100 g of
solution.
• In 100 g of solution à 37.0 g HCl (grams
of solute) and 63.0 g water (grams of
solvent).
• determine the moles of HCl (solute) per
liter of solution
 ACID BASE TITRATION

• Convert the known mass of solution, 100

g solution, to liters of solution, using the
density of the solution
 ACID BASE TITRATION
• General procedure
ü You will obtain the sample in a perkamen
paper.
ü Dissolve the sample in the suitable solvent
and then treat with a suitable treatment
ü NOTE : this is a QUANTITATIVE
measurement. So, VOLUME is important.
 ACID BASE TITRATION
• Use a volumetric pipete not measuring flask. Use
volumetric flask not beaker glass or even
Erlenmeyer.

In case of insoluble substances which are volatile, reaction

requiring heating and substances for which reaction proceed
rapidly only in presence of excess of reagent direct titration will
not possible

Addition of excess but known quantity of the standard

solution to the sample of analyte and after complete
Back titration à reaction the excess of solution (that is not required by
analyte) is titrated with another standar solution
Don't forget to add the indicator!
 ACID BASE TITRATION

Which part is contributing to acidity or basidity of the substance?

 ACID BASE TITRATION
• First case : ASPIRIN (MW : 180.16)
Put your sample into erlenmeyer

Dissolve in 25 mL 0.5 N of NaOH solution

Boil it (about 10 minutes)

Put in a 25 mL of volumetric flask

Add with water until mark sign

Titrate it with 0.5 N of HCl

What happen if an ester boiled with a basic condition?

 ACID BASE TITRATION
• First case : ASPIRIN (MW : 180.16)
Upon boiling with NaOH, aspirin lead to
decomposition by hydrolisis of the ester

Sodium - salicylic acid

Please see your module at page 37!

Then why if you have methylsalicylate, the reflux should be done?

Clue : Consider the structure of methylsalicylate
 ACID BASE TITRATION

2 NaOH

1 mole of Aspirin = 2 mole of Sodium Hydroxide

180.16 grams of Aspirin = 2 mole of Sodium Hydroxide
180.16 grams of Aspirin = 2000 mL Sodium Hydroxide 1 N
180.16 mg of Aspirin = 2 mL Sodium Hydroxide 1 N
90.08 mg of Aspirin = 2 mL Sodium Hydroxide 0.5 N

45.04 mg of Aspirin = 1 mL Sodium Hydroxide 0.5 N

0.04504 grams of Aspirin = 1 mL Sodium Hydroxide 0.5 N

 ACID BASE TITRATION
• Second case : MEFENAMIC ACID (MW : 241.3)
Put your sample into erlenmeyer

Dissolve in 50 mL of warm ethanol

Neutralize the ethanol using phenol red

Take 10 or 25 mL (so you can do duplo/triplo)

Titrate it with sodium hydroxide

How to neutralize ethanol? Why it should be netralize

ACID BASE TITRATION
 ACID BASE TITRATION
• Another case : BENZYL ALCOHOL (MW : 108.06)
Which part contribute to acidity?
When doing titration, why you need to use
acetic anhyride (and pyridine)?
Na2CO3 PP = Phenolphthalein PP = Phenolphthalein
MO = Methyl orange Na2CO3
MO = Methyl orange

NaHCO3 NaHCO3

A B
H2CO3 H2CO3

1st step 2nd step

Volume karbonat = 2A
PP dapat diganti biru timol :merah kresol (3:1)
MO = Metil orange: indigo karmin Volume bikarbonat = (B-2A)
MO dapat diganti bromfenol biru
 NON AQUEOUS TITRATION
Reagent

Preparation of Anhydrous Acetic Acid

•Determine the water content of the glacial acetic acid.
•Add stoichiometric amount of acetic anhydride (to react with the
water contained in the glacial acetic acid) to 1 L of glacial acetic acid.
•Mix thoroughly and allow to stand overnight to ensure complete
reaction between the acetic anhydride and the water present.
Preparation of 0.1 N Perchloric Acid
•Slowly add perchloric acid (72%; 8.5 mL) to glacial acetic acid (900
mL) with continuous efficient mixing.
•Similarly add equimolar of acetic anhydride (to react with water
contained in the perchloric acid and glacial acetic acid); adjust the
volume to 1 litre with glacial acetic acid and allow the solution to
stand overnight before use.
•(Each 1000 mL solution contains 10.05 g HClO4; MW : 100.46).
Preparation of 0.1 N Sodium Methoxide
•Dissolve 2.5 g sodium metal in 150 mL absolute methanol (in ice bath).
•Make up to 1000 mL with water free toluene.
•Add methanol, if necessary, to make a clear solution.
•This solution should be standardized against an acid of primary standard.

Preparation of Mercuric (II) acetate

•Dissolve 6,0 g Hg(C2H3O2)2 in anhydrous acetic acid, adjust the volume to 100 mL.

Indicators
•Crystal violet : 0,5% in anhydrous acetic acid (violet - blue green)
•a-naphtholbenzein : 0,2% in anhydrous acetic acid (blue green - orange)
•Quinaldine red : 0,1% in anhydrous methanol (magenta – almost colourless)
•Thymol blue : 1% in anhydrous methanol or in dimethylformamide
•Azo violet : saturated solution in anhydrous methanol.
 Procedure
Standardization
0.1 N perchloric acid
i.Weigh out 0.7-0.8 gram portions of dried potassium hydrogen phthalate, heat in 120°C
oven for 2 hours, transfer into dry 250 mL flask and dissolve the solid in about 50 mL of
anhydrous acetic acid.
ii.Add 2 drops of crystal violet solution as indicator.
iii.Titrate the solution with the perchloric acid solution to the indicator end point (violet to
blue green).
iv.Perform the titration of 50 ml of anhydrous acetic acid without addition of the analyte.
v.Calculate normality of perchloric acid solution.
1 mole of perchloric acid is equivalent to 1 mole of potassium hydrogen phthalate
0.1 N sodium methoxide
i.Weigh accurately 400 mg benzoic acid, dissolve in 80 mL dimethylformamide. Titrate with
sodium methoxide solution using 3 drops of blue thymol solution as indicator until the color
change to blue.
ii.Perform the titration without the analyte being examined.
iii.Calculate normality of sodium methoxide solution.
1 mole of sodium methoxide is equivalent to 1 mole of benzoic acid
 Determination of Organic
Compound
TITRATION OF A WEAK BASE IN ACETIC ACID
Your sample of base should be dissolved in anhydrous
acetic acid and titrated with the standard HClO4 solution.

When crystal violet is the indicator, the sharpest color

change usually occurs from violet to blue. Whatever color
you take to mark the end point, it is, of course, essential to
carry out a "blank" titration to determine the quantity of
titrant required to cause the indicator to exhibit the color
you assume to indicate the titration end point.
• As is common with most organic solvents,
acetic acid has a significantly higher
coefficient of thermal expansion than water
(e.g., 0.11% vs. 0.025% per degree). In order
to avoid the errors that would result from
thermal fluctuations during volumetric
measurements, it is common practice to use
weight burets for titrations with organic
solvents or to make a correction.
•Antazoline hydrochloride (MW = 301.82)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of antazoline HCl in a 150 mL
titration flask is shaken with ca. 20 mL of anhydrous
acetic acid (warm the solution if necessary). Cool and add
15 mL of 6 % mercuric (II) acetate and 3 drops of crystal
violet. Titrate with 0.1 N perchloric acid. Repeat the
titration at least twice. For correction, perform a blank
titration. Calculate the amount of compound in the
sample.
1 mole of perchloric acid is equivalent to 1 mole of
antazoline HCl
•Athropin sulphate (MW = 676.82)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of athropine SO4 in a 150 mL
titration flask is shaken with ca. 20 mL of anhydrous
acetic acid. Titrate with 0.1 N perchloric acid using
3 drops of crystal violet. Repeat the titration at least
twice. For correction, perform a blank titration.
Calculate the amount of compound in the sample.
1 mole of perchloric acid is equivalent to 1 mole of
athropine SO4
•Bysacodil (MW = 361.40)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of bysacodil in a 150 mL
titration flask is shaken with ca. 20 mL of anhydrous
acetic acid. Titrate with 0.1 N perchloric acid using
3 drops of p-naphtolbenzein. Repeat the titration at
least twice. For correction, perform a blank titration.
Calculate the amount of compound in the sample.
1 mole of perchloric acid is equivalent to 1 mole of
bysacodil
•Chlorpheniramine maleate (MW = 390.87)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of chlorpheniramine maleate in a
150 mL titration flask is shaken with ca. 20 mL of
anhydrous acetic acid. Add 2-3 drops of crystal violet as
indicator and titrate with 0.1 N perchloric acid. Repeat the
titration at least twice. For correction, perform a blank
titration. Calculate the amount of compound in the
sample.

2 mole of perchloric acid is equivalent to 1 mole of

chlorpheniramine maleate
•Codeine phosphate (MW = 397.36)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of codeine phosphate in a 150 mL
titration flask is shaken with ca. 20 mL of anhydrous
acetic acid (warm the solution if necessary). Cool and add
3 drops of crystal violet as indicator. Titrate with 0.1 N
perchloric acid. Repeat the titration at least twice. For
correction, perform a blank titration. Calculate the amount
of compound in the sample.
1 mole of perchloric acid is equivalent to 1 mole of
codeine phosphate
•Dexthromethorpan (MW = 271.4)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of dextromethorpan in a 150 mL
titration flask is shaken with ca. 20 mL of anhydrous
acetic acid (warm the solution if necessary). Cool and add
2 drops of crystal violet as indicator. Titrate with 0.1 N
perchloric acid. Repeat the titration at least twice. For
correction, perform a blank titration. Calculate the amount
of compound in the sample.
1 mole of perchloric acid is equivalent to 1 mole of
dextromethorpan
•Phenylpropanolamine hydrochloride (MW = 187.67)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of phenylpropanolamine
hydrochloride in a 150 mL titration flask is shaken with
ca. 20 mL of anhydrous acetic acid. Add 10 mL of 6 %
mercuric(II) acetate and 2-3 drops of crystal violet as
indicator. Titrate with 0.1 N perchloric acid. Repeat the
titration at least twice. For correction, perform a blank
titration. Calculate the amount of compound in the
sample.
1 mole of perchloric acid is equivalent to 1 mole of
phenylpropanolamine hydrochloride
•Phenytoin (MW = 252.27)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of phenytoin in a 150 mL
titration flask is shaken with ca. 20 mL of freshly
dried dimethylformamide and add 3 drops of azo
violet as indicator. Titrate with 0.1 N sodium
methoxide until the color change to blue. Repeat the
titration at least twice. For correction, perform a
blank titration. Calculate the amount of compound
in the sample.
1 mole of sodium methoxide is
equivalent to 1 mole of phenytoin
•Allopurinol (MW = 136.11)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of allopurinol in a 150 mL
titration flask is shaken with ca. 20 mL of freshly
dried dimethylformamide and add 3 drops of thymol
blue as indicator. Titrate with 0.1 N sodium
methoxide. Repeat the titration at least twice. For
correction, perform a blank titration. Calculate the
amount of compound in the sample.
1 mole of sodium methoxide is
equivalent to 1 mole of allopurinol
•Barbital (MW = 184.19)
A quantity of the sample (accurately weighed)
containing ca. 1 meq of barbital in a 150 mL
titration flask is shaken with ca. 20 mL of freshly
dried dimethylformamide and add 3 drops of thymol
blue as indicator. Titrate with 0.1 N sodium
methoxide. Repeat the titration at least twice. For
correction, perform a blank titration. Calculate the
amount of compound in the sample.
1 mole of sodium methoxide is
equivalent to 1 mole of barbital