Neutralization Reactions In Non-aqueous medium

Non-aqueous titration: deals with the analysis in a medium completely free from water. -using solvents other than water. -Uses: Determination of very weak acids and bases.

II-Bronsted-Lowry Theory: 1-An acid is defined as proton donor. 2-A base is defined as proton acceptor. 3-Acid-base reaction is a proton transfer from acid to base. HA + B → BH+ + A- Acid base conj. Acid conj. Base *انا مقدرش احدد المادة اذا كانت حمض او قاعدة , بحددها على حسب H2Oهيا بتتفاعل مع ايه , و المثال على كدة ال

CH3COOH + NH3 → NH4+ + CH3COO- H2O + CH3COOH→ CH3COO- + H30+ H2O + NH3 → NH4+ + OH- CH3COOH + NH3 → NH4+ + CH3COO- From these equations it is clear that acidity and basicity of a substance and a solvent are relative to each other i.e. substance can react as a base in presence of more proton donor one and as an acid in presence of a more proton acceptor. H2O in presence of proton acceptor  H2O is acidic H2O in presence of proton donor  H2O is basic

Acidity and basicity of a substance is relative to the medium. Substance acts as an acid in the presence of proton acceptor. Substance acts as an base in the presence of proton donor.

HCl not acidic to dry L.P. Why? Ex.1 HCl not acidic to dry L.P. Why? Due to the absence of water which is the H+ acceptor. * V.imp note: تاني يتم تحديد حسب الوسط الموجود فيه base or acidic المادة CH3COOH reacts as acid in pyridine CH3COOH reacts as base in HClO4, H2SO4 CH3COOH + HClO4 ClO4- + CH3COOH2+ *Strongest acid in non aqueous medium Ex.2

Classification of acids and bases according to Lewis Theory: A-Defined acids as that accept a lone pair of electrons (unshared) to form co-ordinate covalent bond. Examples: Cl 1-Uncharged molecules B- Cl , AlCl3 , ASCl3 Cl , BF3 , AlBr3 2-Cations Ag+, Cu2+, Zn2+, Co2+ coordinate bond الحمض: هي المادة التي تقبل زوج من الالكترونات لتكوين رابطة ال

B-defined a base as electron-pair donor to form co-ordinate covalent bond. Examples: Me 1-Uncharged molecules: NH3 and :N Me Me 2-Ions: Cl-, Br-, OH-, SO42- Coordinate القاعدة : هي المادة التي تمنح زوج من الالكترونات لتكوين رابطة ال

Roles of solvent in non-aqueous titrations: 1-relative acidity and basicity: According to Bronsted theory acidity and basicity of substance is relative to the solvent. If substance is more acidic than the solvent, it will behave as an acid. If more basic than solvent, behave as a base e.g. potassium acid phthalate dissolved in water acts as primary acid, while in glacial acetic acid acts as a base and used as primary basic substance.

Levelling effect & differentiating ability بعلي المستوى of non-aqueous solvents: HCl , CH3COOH in NH4OH HCl , CH3COOH in H2O سحبتNH4OH* من H+ Acetic acid and HCl بنفس القوة و بالتالي جعلت بنفس المستوى NH4OH attack the same no. of H+ so both acids have the same acidity H2O اما* H+سحبت HCl من بشكل اقوى من ال Acetic acid و بالتالي H2O فرقت بين الحمضين HCl donate H+ more than CH3COOH NH4OH: leveling & non-differentiating H2O: non-leveling & differentiating

2-Levelling effect of solvents: It is the ability of solvent to increase the strength of weak acids or weak bases to reach that of strong ones, respectively. Basic solvents have a levelling effect on weak acids, generally strong acids gives it’s H+ easily, while the basic solvent attracts H+ easily from the weak acid so that both, the strong & weak acids, will have the same strength. احنا عارفين انو الحمض القوي بيفقد بروتن بسهولة , و لكن الحمض الضعيف ميقدرش يفقد البروتن بسهولة و و بالتالي لما استخدم قاعدة قوية , هتقدر تسحب البروتن من الحمض الضعيف و هتخلي الحمض الضعيف يبان زي الحمض القوي

Also acidic solvents have levelling effect on weak bases, normally strong base attracts H+ from the solvent, while in weak bases the acidic solvent donates or gives its proton easily to it , i.e. weak base and strong base are of equal strength. نفس الفكرة لما يكون المذيب حمض قوي هيمنح بروتن بسهولة , فلما يكون عندي خليط من قاعدة قوية و اخرى ضعيفة , فطبيعي القاعدة القوية هتستقبل بروتون بسهولة , و القاعدة الضعيفة الحمض القوي هيجبرها على استقبال البروتون بنفس كفاءة القاعدة القوية Examples: 1-Glacial acetic acid has levelling effect on bases such as amines i.e. they are strong bases in acetic acid. 2-Liquid ammonia and ethylene diamine which are more basic than H2O have levelling effects on both mineral and carboxylic acids (acetic), they all nearly have the same strength in such solvents.

3-Differentiating effect of solvents: i.e. the ability of the solvent to differentiate between the strength of acids and bases: Examples: 1-Water is differentiating solvent for amines (weak bases) they are much weaker than mineral alkalies ( NaOH & KOH). Levelling نفس فكرة ال بس الاختلاف هنا ان المذيب المستخدم في ال Differentiating اما يكون قاعدة ضعيفة او حمض ضعيف 2-When HClO4, HCl and HNO3 are dissolved in glacial acetic acid it is only HClO4 is the strong acid i.e. acetic differentiates between strength of mineral acids.

Solvent properties that affect levelling & differentiating effect of solvent and completeness of neutralization reactions.

1) Acid-base properties of solvent relative to the solute 1) Acid-base properties of solvent relative to the solute. Solvent such as formic, sulphuric and glacial acetic acid is proton donor more than being proton acceptor i.e. acidic in nature having levelling effect on bases e.g. aniline weak base in water (Ka = 10-10) can not be directly titrated, whoever it is strong base in glacial acetic acid and can be directly titrated.

Solvents such as ethylene diamine, n-butylamine and liquid ammonia are more proton acceptor than donor i.e. basic in nature have levelling effect on weak acids as phenol which has Ka = 10-10 in H2O, but strong enough in such solvents to be directly titrated. H2O في بعض القواعد , الاحماض بتبان بصورة ضعيفة جدا في ال ( titration ) و بالتالي مقدرش اعملها Strong basic solvent و عشان احل المشكلة , بأضع الحمض الضعيف في Acidity علشان أزود ال Strong acidic base للحمض الضعيف. و أضع القاعدة الضعيفة في للقاعدة الضعيفة و بالتالي أقدر أعمل Bascicity علشان أزود ال Titration

2) Autoprotolysis constant (Kap) of the solvent Autoprotolysis is self-dissociation of solvent 2HA → [A-.HAH+] → A- + H2A+ Kap = [A-] [H2A+] في مواد عندها خاصية انها في نفس الوسط ممكن تبقى حمض و ممكن تبقى قاعدة في نفس الوقت . 2 NH3 → NH4+ + NH2- 2 CH3OH → CH3OH2+ + CH3O- H2O + H2O → H3O+ + OH- 2 CH3COOH → CH3COOH2+ + CH3COO- Conj. Acid Conj. Base i.e. two solvent moles interact one acts as a proton donor and the other acts as proton acceptor.

The smaller the autoprotolysis constant Kap of solvent the greater will be its ability to be differentiating. كل ما كان Kap عالي , ده دليل على ان المادة ليها قدرة عالية انها تعطي Conjugate base and conjugate acid The smaller the Kap the more complete the reaction because solvents with high Kap will produce a considerable amount of ionic species which will compete with substance to be determined for the protons. (decrease competition of conjugate base of the solvent with the basic sample for protons and also to decrease competition between conjugate acid of the solvent and acidic sample).

Kdiss DE Kap differentiating 3-The dielectric constant (DE): It is the ability to separate positively charged ions from negatively charged ions. Solvent with high DE minimum work is required for such separation. The higher DE of solvent the greater the separations by decreasing force of attraction between +ve and –ve ions. هي قدرة المذيب على فصل الايوتات السالبة من الايوتات الموجبة كلما زادت DE, كلما زادت قدرة المذيب على فصل الايونات عن بعدها و العكس صحيح - H2O is unique solvent it has low Kap but highest DE of all solvent which allows completeness of reactions. Kdiss DE Kap differentiating

Classifications of solvents used in non-aqueous titrations Aprotic: ليس لها قدرة على أن يمنح او يستقبل بروتونات بيستخدم لمنع تأين المذيب ليعطي قراءة End point دقيقة - Acetic acid فمثلا أنا لما أستخدم كمذيب ,احنا عارفين ان حمض الاسيتك ليه القدرة على انتاج قاعدة و حمض مرافقين , Titration و بالتالي لما أعمل Endpoint قبل titrantلل هتتفاعل مع Conjugated base and conjugated acid و بالتالي قراءة دقيقة مش هتبقىTitration ال ليها قدرة انها تكون حمض او قاعدة حسب الوسط الموجود فيه 1) Amphiprotic Acts as H+ donor & acceptor Acts as acid &base (amphoteric). e.g. H2O (neutral), CH3COOH (acidic, but has no definite acidic characters) , NH3 (basic, but has no definite basic characters). 2) Aprotic Can’t accept or donate H+ (inert solvents). No autoprotolysis, low DE. Used to prevent solvolysis of the reaction products near e.p so more sharp e.p. e.g. Hydrocarbon (HC), halogenated HC ليها قدرة على استقبال بروتونات بس مش محتاجة تاني 3) Protophilic definite basic characters without any acidic characters. No autoprotolysis Exert levelling effect on weak acids. e.g. ethylene diamine , pyridine , DMF, DMSO, butylamine. 4) Protogenic definite acidic characters without any basic characters. No autoprotolysis Exert levelling effect on weak bases. e.g. H2SO4,HClO4.

Choice of solvents: Best solvent has the following characters: 1-Lowest possible Kap↓ 2-Highest possible DE↑ 3-Acidic solvents are used to dissolve basic substances to increase their dissociation and strength, therefore allow complete reaction, similarly basic solvents are used for acidic substances 4- Substance must be soluble in the chosen solvent.

Advantages of non aqueous titrations : 1.Very weak acids or bases directly titrated in non-aqueous medium using leveling solvent. 2.Sharper e.p obtained using aprotic solvent which hinder solvolysis of the product of the reaction. 3. Differentiating solvents enables differential titration of mixture of acids or bases as they increase the difference between their dissociation constant to be 104 at least. 4. If the sample insoluble in H2O could be dissolved in non-aqueous solvent. 5. Low surface tension small droplet size< aqueous so more accurate volume of titration.

Disadvantages of non aqueous titrations : Non-aqueous solvents have high thermal coefficient, therefore titration must be carried out at the same temp. of preparation of standard or the volume of titrant should be multiplied by C.F. C.F = 1 ± 0.001 t˚ C t˚ C = difference in temp. at which standard prepared & used 2. Non-aqueous titration is non specific (any acidic or basic impurities can interfere. Titration لازم لما نعمل Non- aqueous و لما نستخدم Solvent يبقى في نفس درجة الحرارة اللي اتجهز فيها المذيب ده.

I-Determination of basic substances: Application of Non-aqueous titration I-Determination of basic substances: 1-Solvents used: glacial acetic acid, less common formic acid. free from H2O Acetic acid must be free from water. Therefore water content of acetic acid must be carefully determined (using Karl-Fischer reagent), then the solvent is refluxed with a suitable amount of acetic anhydride for removal of water.

2-Titrant: acetous perchloric acid, 0 2-Titrant: acetous perchloric acid, 0.1N HClO4 in glacial acetic acid standardize against primary standard base KHphthalate. 3-Detection of the end point (a) Instrumental methods (potentiometrically): measurement of potential of ion selective (glass electrode) which responds to the concentration of solvated protons. (b) Visual method: using acid-base indicators e.g. Acetus crystal violet: violet to bluish green.

Applications: Weak bases e.g. amines, purine bases such as coffiene, theophylline …, alkaloids, urea, amides… i.e. all can be titrated in glacial acetic using acetous perchloric and crystal violet indicator.

Primary, secondary, tertiary Amines Mixtures: Total amines directly titrated with acetous perchloric in glacial acetic acid using crystal violet , according to the following equations: RNH2 + HClO4 → RNH3+ + ClO4- R2NH + HClO4 → R2NH2+ + ClO4- R3N + HClO4 → R3NH+ + ClO4-

Determination of tertiary amine only: Equal amount of the mixture (used in (1) is refluxed with acetic anhydride where primary and secondary amines are acetylated only. The remaining tertiary amine is determined by titration against hydrochloric acid in isopropanol.

+ RNH2 CH3CO.NHR + CH3COOH + R NH CH3CO.NR2 + CH3COOH R

3-Determination of secondary and tertiary amines together: Equal volume of sample is heated with salicylaldehyde which forms schiff’s base with primary amine only. The product is titrated with hydrochloric acid in isopropanol, mls = tertiary + secondary amines + RNH2 + H2O

Calculation: Volume of standard perchloric in (2) = tertiary amine Volume of standard in (3) – (2) = secondary amine Volume of standard (1) – (3) = primary amine

B. Amino acids Amino acids such as alanine, glycine…in glacial acetic, dissociation of -COOH group is suppressed while –NH2 group is levelled up and can be titrated with acetous perchloric using crystal violet. + HClO4 + ClO4-

II-Determination of Acidic substances: Solvents: Benzene-Methanol (or Ethanol) for moderate strong acids Methyl isobutyl ketone ,acetone and acetonitrile have differentiating effect on acids and can be used for step wise titration of mixed acids leveling solvents e.g. ethylene diamine, DMF, pyridine, butylamine

Titrant: Sodium Methoxide (NaOCH3), NaOC2H5 (ethoxide) in methanol or ethanol-benzene mixture, used for carboxylic and acidic substance of similar strength. Prepared by dissolving Na° in the corresponding alcohol. Standardize against benzoic acid Indicators: Thymol blue changes its colour from yellow in acid side to blue in alkali one. Azo violet changes its colour from red to blue.

Determination of sulphonamides: Sulfonamides contain – NH2 which is a basic group and –SO2-NH- which is weak acidic group. i.e., sulfonamides are amphoteric therefore we have to add strong basic solvent to increase its acidic character. -Solvent: DMF, butylamine -Standard: Na methoxide. -Indicator: thymol blue or azo-violet. OR Or for NH2 (basic) sulfonamides add strong acidic solvent to increase its basic character -Solvent: glacial acetic acid. -Standard: perchloric acid.

Weak acids Weak bases Solvent ethylene diamine, DMF, pyridine, butylamine Glacial acetic acid Titrant CH3ONa, C2H5ONa, tetrabutyl ammonium hydroxide Acetus perchloric acid Standardization of titrant Against benzoic acid Against primary standard base KHphthalate Detection of end point Potentiometrically or by using acid-base indicators, e.g., thymol blue (yellow to blue) or azo violet (red to blue) Potentiometrically or by using acid-base indicators, e.g., acetous crystal violet (violet to bluish green) Examples Phenol, sulphonamides, amino acids Amines, sulphonamides, amino acids, alkalie metal salts and ammonium salts of carboxylic acids eg. acetate, oxalate, benzoate, salicylate, citrate.