TITRATIONS IN NON-AQUEOUS SOLVENTS

B.KIRUTHIGALECTURER

DEPT OF PHARMACEUTICAL CHEMISTRY

WATER, as SOLVENT

ADVANTAGES: ☻ cheap, clean (can easily be purified)

☻ high relative permittivity (ε): good solventDISADVANTAGES: 0 - 100 °C temperature range

apolar substances can not be disolved

Kw = 10−14, therefore Kd ≤ 10−7 unmeasurable

WATER actively participates in all type of reactions:

- acid and base: acid-base reactions take place through connectionto water first (amphoteric)

- complex formation: cations: aqua complexanions : H-bond

- precipitation: dissolves precipitate of ionic lattice (high hydration energy)

- oxidant and reductant; range of redox potential: 0 −1,23 V theoretical-0.8 − 2,1 V practical

CLASSIFICATION of SOLVENTS

ACIDIC (protogene): H2SO4, CH3COOH, HCOOH, acetone proton donor

AMPHOTERIC (amphiprotic): H2O, alcohols, acetonitrile

BASIC (protophyl): pyridine, liq. NH3, amins, dioxane proton acceptor

APROTIC: liquid SO2

INERT: CCl4, CHCl3, benzene, carbohydrates

REACTIONS in NON-AQUEOUS SOLUTIONS

AUTOPROTOLYSIS EQUILIBRIA determines the ionic product :

2 H2O H3O+ + OH− 10−14 0 - 14 7

☻ neutralization (protolytic solvents) ≈ 90 %

☻ complex formation, precipitation, redox ≈ 10 %

solvent K pH scale neutr. point

2 CH3COOH CH3COH2+ + CH3COO− 10−13 0 - 13 6,5

2 NH3 NH4+ + NH2

− 10−32 0 - 32 162 C2H5OH C2H5OH2

+ + C2H5O− 10−19 0 - 19 9,5

− pH scale depends on the value of KHL = [H2L+][L−]

NEUTRALIZATION ANALYSIS in NON-AQUEOUS SOLVENTS

REACTIONS in NON-AQUEOUS MEDIUM

E.g. HClO4 + pyridine (Py) in glacial acetic acid

acid: HClO4 + CH3COOH ClO4− + CH3COOH2

+

K = [CH3COOH2+][CH3COO−] = 10−13

base: Py + CH3COOH PyH+ + CH3COO−

ClO4− + CH3COOH2

+

PyH+ + CH3COO− PyH+ ClO4− + 2 CH3COOH

2 CH3COOH

− Brönsted equation can be used

− reactions take place through reaction of acids or bases with the solvents

ADVANTAGES of USING NON-AQUEOUS SOLVENTS

☻ 1. More than 3 acids/bases can be measured in mixture due to the wider pH range

compared to water

E.g.methyl-ethyl-ketone water0 - 25.7 pH range 0 - 14 pH range5 comp. measurable max. 3 acids (3 x ΔpH(4) = 12)HClO4 - HCl - Salicylic acid - Acetic acid - Phenol(can titrated with TBAH (C4H9)4N+OH−)

☻ 2. Differentiation - levelling effect (Kd ~ 10−12 can be measured)

a) Differentiation effect:in water: HClO4 ≈ HCl ≈ HNO3

in CH3COOH: HClO4 > HCl > HNO3

in HF: medium > weak > base

acidConclusions:Strong acids (in water) can separetely be measured in acidic solventsStrong bases - ″ - in basic solvents

in water: HCl > CH3COOH > benzoic acidb) Levelling effect:

in pyridine: HCl ≈ CH3COOH ≈ benzoic acid

EXPLANATION by the protonaffinity

ADVANTAGES of USING NON-AQUEOUS SOLVENTS

Conclusions:Weak acids (in water) can be measured in basic solventsWeak bases - ″ - in acidic solvents

☻ 3. Determination of organic acids and bases which have a limited solubility in water.

☻ 4. Application of new reagents and indicators is possible due to

ADVANTAGES of USING NON-AQUEOUS SOLVENTS

expensive

volatile

toxic

removal of water is necessary, can take water (humidity) from the air

DISADVANTAGES of USING NON-AQUEOUS SOLVENTS

− HClO4 in glacial acetic acid− HCl in propylene-glycol /chloroform mixture

STANDARD SOLUTIONS

ACIDIC :

BASIC : − TBAH (C4H9)4N+OH−) in pyridine− KOH in ethanol

application: - weak bases: Kb : 10−7 − 10−12

e.g. aromatic amines, amides, alcaloides, etc.- high-molecular-weight organic bases, that have limited solubility in water

E.g. Determination of „Lidocain” (Lidocainum Ph.Hg. VII.)

NH CO CH2 NC2H5

C2H5

CH3

CH3

application: - weak acids: Ka : 10−7 − 10−12

e.g. carboxylic acids, phenols, enols etc.- high-molecular-weight organic acids, that have

limited solubility in water

END POINT DETECTION

CHEMICAL:(INDICATORS)

− crystal violet (in glacial acetic acid)

INSTRUMENTAL: − potentiomety : glass electrode in glacial acetic acid− conductometry

− phtaleins (phenolphtalein) (e.g. in pyridine)− azo compounds (methyl red) (e.g. in alcohol)

R +|C-R|R

ibolya

R + R-H 2+

| |C-R + H+ C - R| |R R

ibolya zöldeskék

R + R-H 2+ R-H 3+

| | |C-R + H+ C - R + H+ C-R| | |R R R-H

violet green yellow

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