Non-aq. Titration.pdf

Types of Solvents, Indicators used, Examples

1. NON AQUEOUSTITRATION
By
Dr. Jasmine Chaudhary
Associate Professor
MMCP, MM(DU)
Mullana

2. CONTENT
Introduction
Types Of Solvents
1. Aprotic solvents
2. Protophilic solvents
3. Protogenic solvents
4. Amphiprotic solvents
Non Aqueous Titration Of Weak Acids
Non Aqueous Titration Of Weak Bases

3. Non-aqueous titrations
Titrations involving any non-aqueous solvent instead of water are known
as non-aqueous titrations.
Reasons for Non-aqueous titrations
The reactant is insoluble in water.
The reactant is reactive with water (i.e. undergoes chemical
decomposition in water)
The reactant is too weak acid or weak base (water due to its
amphiprotic nature will compete with the sample)

4. Nonaqueoustitrationarethoseinwhichtitrationofweaklyacidicorbasic
substancesarecarriedoutusingnonaqueoussolventssoastogetsharpend
point.
ConditionsRequired
Moistureandcarbondioxideshouldbeavoidedusingnonaqueousprocedures
(Moistureshouldbeheldtolessthan0.05%.)
Standardization&titrationshouldbecarriedoutasfaraspossibleatthesame
temperature.
Innonaqueoussolventstheaciditydecreasesinthefollowingorder
HClO4>HBr>H2SO4>HCl>HNO3

5. Watershouldnotbepresenteveninminuteamountsbecause
Ifwearedoingtitrationofweakacid,waterwillactasstrongacid
ascomparedtosampleanddonatesprotonstobase.Thusthereis
interferenceinreactionofweakacidwithbase.
Ifwearedoingtitrationofweakbase,waterwillactasstrongbase
ascomparedtosampleandacceptsprotonsfromacid.Thusthere
isinterferenceinreactionofweakbasewithacid.

6. Types of Non-aqueous solvents
The solvents are divided into 4 groups
Aprotic solvents
Protophilic solvents
Protogenic solvents
Amphiprotic solvents

7. Protogenic solvents
Theseareacidicinnatureanddonateprotons.
Theyhavehighdielectricconstantandionisedbecauseoftheir
strengthandabilitytodonateprotons.
Theyenhancebasicityofweakbases.
Ex:-Sulphuricacid,Formicacid,GlacialAceticacid,Propionoic
acid,Aceticanhydrideetc.
Protophillicsolvent
Basicincharacterandenhanceacidityofweakacids.
Theyacceptprotonsfromacidstoformsolvatedproton
HB+Sol.⇌SolvatedH++B-
Acid+Basicsolvent⇌Solvatedproton+Conjugatebaseofacid
Ex:-Acetone,ether,pyridine,liquidammonia,DMF

8. Aprotic solvents (Inert solvents)
Aproticsolventsareneutralandchemicallyinert.
Havelowdielectricconstant,donotreactwitheitheracidsorbases
andthereforedonotfavorionization.
Thepicricacidgivesacolorlesssolutioninbenzeneortoluenewhich
becomesyellowonaddinganilineshowsthatpicricacidisnot
dissociatedinbenzeneortoluenesolution.
Thistypeofsolventsneitheracceptnordonateprotons
Ex:-Benzene,dioxan,chloroform,ethylacetate,carbontetrachloride.

9. Amphiprotic solvents
Have both protophillicand protogenicproperties.
Can accept as well as donate protons.
Ex:-water, alcohols, acetic acid
CH
3COOH ⇌H
+
+ CH
3COO
-
Heretheaceticacidisfunctioningasanacid.
Ifaverystrongacidsuchasperchloricacidisdissolvedin
aceticacid,thelattercanfunctionasabaseandcombinewith
protonsdonatedbytheperchloricacidtoformprotonatedacetic
acid.,anoniumion”
HClO
4⇌H
+
+ ClO
4
-
CH
3COOH + H
+
⇌CH
3COOH
2
+
(onium ion)
Since the CH
3COOH
2
+
ion readily donates its proton to a base, a
solution of perchloric acid in glacial acetic acid functions as a
strongly acidic solution.

10. Whenaweakbase,suchaspyridineisdissolvedinacetic
acid,equivalentamountofacetateionsareproducedwhich
havemoretendencytoacceptprotons.
Therefore, a solution of a weak base in acetic acid can be
titrated with perchloric acid in acetic acid to obtain a sharp
endpoint.
HClO
4+ CH
3COOH ⇌CH
3COOH
2
+
+ ClO
4
-
onium ion
C
5H
5N + CH
3COOH ⇌C
5H
5NH
+
+ CH
3COO
-
Acetate ion

11. Selection of solvent
The solvent selected should be soluble to both the drug sample
and titrant.
It should be selected based on the nature of drug i.e. whether it
is weak acid or weak base. For example, if sample is weak
acid, then basic solvents like DMF, pyridine is used or vice-
versa.
The solvent selected should not react with the drug sample.
The solvent should be readily available, of low toxicity,
inexpensive.

12. The most commonly employed non-aqueous solvents are
•Glacial Acetic acid (Glacial ethanoic acid): used for titration of
weak bases, Nitrogen containing compounds.
•Acetonitrile(generally used along with chloroform and acetic
acid): Used in titration of metal ethanoates with perchloric acid.
•Alchohols(Methanol/Ethanol/Butanol/Glycols): For soaps & salts
of organic acid
•Dioxane(Can be used as replacement of glacial acetic acid)
•DMF(Dimethyl Formamide): Used for titration of amides and
benzoic acid.

13. LevellingEffect
Theacidityoftheweakacidscanbeenhancedusingbasicsolventsbecausethe
basicsolventhashigheraffinitytotakeupprotonsfromacid.
So,aceticacidbehavesasastrongacidinammoniasolution.
Alsothebasicityoftheweakbasescanbeenhancedinthepresenceofacidic
solvent.Thisiscalledthelevellingeffectofthesolvent.

14. DETERMINATION OF END POINT
Potentiometrictitration
Indicatormethod
Potentiometrictitration:
Theendpointisdeterminedbyusingindictorelectrode(glass
electrode)andreferenceelectrode(saturatedcalomelelectrode).
Indicatormethod
Visualindicatorareconsideredasmostsuitableforthe
detectionofendpointinnon-aqueoustitration.

15. Theimportantindicatorusedfornon-aqueoustitrationarefollows:-
Crystalviolet(0.5%w/vsolutioninGAC)
Itisconsideredasmostcommonindicatorintitrationofbases.
Itisusedas0.5%solutioninglacialaceticacid,itgivesvioletcolourin
basicmediumandyellowishgreeninacidicmedium.
Itismostwidelyuseforthetitrationofpyridinewithperchloricacid.

16. ThymolBlue(0.2%w/vsolutioninmethanol)
Thecolourchangeisfromyellowtoblue.
Usedasanindicatorforthetitrationofsubstancesactingasacidsin
DMF.
QuinaldineRed(0.1%w/vsolutioninethanol)
Itisalsoemployedasindicatorindeterminationofdrugsubstancein
dimethylformamide(DMF).
Thecolourchangeisfrompurpleredtopalegreen.
Quinaldine Red
Thymol Blue

17. OracetBlueBIndicator(0.5%w/vsolutioninglacialaceticacid)
Itgivesbluecolorinbasicmediumwhilepinkcolorinacidicmedium.
MethylRedIndicator(0.2%w/vsolutionindioxane)
Itchangesyellowtoredcolor

18. Titrants for Non-Aqueous Titration
Perchloric acid in acetic acid
Amines, amine salts, amino acids, salts of acids
Potassium Methoxide or Sodium Methoxide in Toluene-
Methanol

19. Non Aqueous Titration of weak Bases
Titrant
Generally0.1-0.05Nsolutionofperchloricacidinglacial
aceticacidordioxane.
Preparationoftitrant(0.1NHClO4)
Dissolve8.5mlof70-72%perchloricacidwithstirringina
mixtureof500mlGACand25mlaceticanhydrideandthen
makeupthevolumetoILwithGAC.
Keepthesolutionforatleast24hoursandthencheckthe
moisturecontent.Itshouldbebetween0.02-0.05%otherwise
itshouldbeadjustedwithaceticanhydrideasaceticanhydride
willneutralizethetraceamountofwaterpresentintitrant
whichotherwisewouldinterferewithendpoint

20. Standardizationofprepared0.1Nsolution
Itisdonebyusingpotassiumhydrogenphthalateasprimarystandardandendpointis
determinedeitherpotentiometricallyorbyusing0.5%crystalvioletinGACasindicator
whichwillchangethecolorfromviolettoturqoise(bluishgreencoloratendpoint).
Accurately0.7gofpotassiumhydrogenphthalateisdissolvedin50mlofglacialacetic
acid.Towhichfewdropsofcrystalvioletindicatorisaddedandthenthesolutionis
titratedwithpreparedperchloricacidsolution.
Performblankdeterminationusingonly50mlglacialaceticacidwithindicatorand
withoutsampleandobservetheperchloricacidusedforneutralization.
Subtractthisamountfromvolumeobservedforperchloricacidwithsample.
Eachmlof0.1NHClO4acidisequivalentto0.02042gofpotassiumhydrogenphthalate.
Normalityofperchloricacid=Wtofpotassiumhydrogenphthalatetaken/Volof
perchloricacidx0.02042

21. Apparatus
Erlenmeyerflaskwithglassstopperisusedastitrationvessel.
(AnErlenmeyerflask,alsoknownasaconicalflaskmadeupof
borosilicateglass,isawidelyusedtypeoflaboratory
flaskwhichfeaturesaflatbottom,aconicalbody,anda
cylindricalneck.ItisnamedaftertheGermanchemist...
Burettewithteflonstopcorkisusedforcarryingouttitration

22. Solvents
Neutralsolvents:
Ex:Alcohol,Chloroform,Benzene,Chlorobenzene
Acidicsolvents:
Ex:-Formicacid,glacialaceticacid,propionicacid
Indicators
Ex:-OracatblueB(0.5%w/vinGAC)
Crystalviolet(0.5%w/vinGAC)
1-naphtholbenzein
Methylred,methylorange(0.1%inanhydrousmethanol)

23. Electrodes
(For potentiometricdetermination of end point)
Combinationofsaturatedcalomel(mercuryelectrode)and
glassindicatorelectrodesareused.
Aq.SaturatedKClsolutionincalomelelectrodecanbe
replacedwithsaturatedsolutionofKClinGACor
anhydrousmethanol.
Examples of Titrations of Weak Bases
TitrationofEphedrinealkaloidinGlacialAceticAcidby
acetousperchloricacid.
TitrationofEphedrinealkaloidinDioxanebyacetous
perchloricacid.

26. Non Aqueous titration of weak acids
Manyweaklyacidicsubstances(alcoholoraproticsolvent)
canbetitratedinanappropiatenonaqueoussolventswith
asharpendpoint.
Ex:-acidichalides,acids,aminoacids,enols(barbiturates,
xanthines),phenols,pyroles,sulphonamidesetc,.
1) Solvents used in the titration of weak acids:
Ex:-Ethylenediamine,n-butylamine,morpholine
2) Titrant used in the titration of weak acids:
Ex:-sodium methoxide, lithium methoxide,
potasium methoxide ,tetrabutyl ammonium hydroxide etc.
3) Indicators used in the titration of weak acids
Ex:-azo violet.thymol blue,thymolphthalein.,O-
Nitro aniline

27. Methoxides of alkali metals
Add 2g Na, 0.6g Li in mixture of 40ml ethanol + 50ml of
dry benzene in Erlenmeyer flask
Add small amount of methanol to produce color solution
Add benzene slowly to prepare cloudy solution.
Then again add methanol followed by benzene until 1L of
solution is prepared.
Standardize it using benzoic acid in DMF as primary
indicator and 0.5% thymol blue in anhydrous methanol
as indicator.

28. REFERENCES:
Textbook of QUANTITATIVE CHEMICAL ANALYSIS :
VOGEL’S
PHARMACEUTICAL TITRIMETRIC ANALYSIS:
A.A NAPOLEON