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Organic Acids & Organic Bases

1. Acidity

1.1 Introduction

Acidity of an acid HA is the measure of the position of following equilibrium : HA + H2O Acidity is measured by Ka =
[ H 3O ][ A ] [ HA]

H3O+ + A-

The further the equilibrium lies to the right, the lower/higher the degree of dissociation of HA and thus the stronger/weaker acid HA is. The extent of equilibrium is determined by the following factors : 1. Strength of H-A bond

Weaker H-A bond H-A bond easier/more difficult to be broken higher/lower degree of dissociation of HA stronger/weaker acid

2. Relative stability of A- with respect to HA Equilibrium constant and thus extent of equilibrium is determined by the relative stability between reactants and products. Since most organic acids are strong/weak, the undissociated acid is relatively less/more stable and occurs higher/lower in the enthalpy level diagram, and the conjugate base is relatively less/more stable and exists at a higher/lower position in the diagram. enthalpy enthalpy enthalpy

If acid is stabilized

Normal Case

If conjugate base is stabilized

If acid is stabilized with respect to conjugate base, dissociation process has a more/less positive enthalpy change of reaction dissociation process is more/less favourable stronger/weaker acid If conjugate base is stabilized with respect to acid, dissociation process has a more/less positive enthalpy change of reaction dissociation process is more/less favourable stronger/weaker acid

The strength of an acid is a relative term only. There is no sense in saying an acid is strong or weak, an acid can only be said to be stronger (or weaker) than some other acid.
Chemistry/Organic Acids & Organic Bases 1

7, so they have no effect on litmus paper.

1.2 Acidity of Alkanols Alcohols are very weak acids, slightly weaker than water, with Ka values around 10-16. Their pHs are essentially The acidic properties of alcohol can only be brought out by very strong base. In fact, alcohols do not react with common bases like sodium hydroxide, sodium hydrogencarbonate and sodium carbonate. 1.2.1
Alcohols react with sodium metal to give hydrogen gas. 2ROH + Na 2RO-Na+ + H2 sodium alkoxide

Reaction with Sodium Metal

This reaction is much milder than the reaction between sodium and water commonly used as a safe way to dispose of sodium metal

Example :

2CH3CH2OH + 2Na 2CH3CH2O-Na+ + H2 sodium ethanoxide The anion is named as alkoxide, by replacing the -ol in alcohol by -oxide.

Naming :

Chemistry/Organic Acids & Organic Bases

1.3 Acidity of Phenols 1.3.1 Introduction Phenols are much stronger acid than alcohols.

OH + H2O phenol phenoxide ion

+ O- + H 3 O

Ka 10-10

OH + H2O

O-

+ H 3 O+
Ka 10-16

alcohol
Reason :

alkoxide ion

O-

For

phenols, phenoxide ion is extra-stabilized by extended overlap with electron cloud in the ring negative charge on oxygen is dispersed to the ring system phenoxide ion is stabilized phenol is a stronger acid

For alcohols, the alkoxide ions are not stabilized alcohols are much weaker acids Strictly speaking, extended delocalization occurs both in phenol and phenoxide ion, i.e. both of them are extra-stabilized. However, as phenoxide ion is less stable, the extended delocalization and therefore extrastability will manifest itself to a greater extent in it, than in the more stable phenol molecule. Therefore, the overall effect is stabilization in phenoxide ion, and phenol is more acidic than normal alcohols. enthalpy

Remarks :

In fact, since all organic acids are weak, and the conjugate bases are always much less stable than its parent acid, we will always focus on stabilization effect on the much less stable conjugate base and ignore stabilization effect on the much more stable parent acid.

Chemistry/Organic Acids & Organic Bases

1.3.2

Like alcohols, hydrogen gas is given out.

Reaction with sodium

OH + Na

O-Na+ + H2 sodium phenoxide

Unlike alcohols, phenols are acidic enough to react with sodium hydroxide to give water. This serves as a method to separate a mixture of insoluble alcohol and phenol. Sodium phenoxide is an ionic compound quite soluble in water.

1.3.3

Reaction with sodium hydroxide

OH + NaOH

O-Na+ + H2O sodium phenoxide

Chemistry/Organic Acids & Organic Bases

1.4 Acidity of Carboxylic Acids 1.4.1 Carboxylic Acids vs Alkanols 1.4.1.1 Experimental Observations Carboxylic acids are much more acidic than any class of organic compounds. They are 1010 - 1011 times stronger acid than ROH, but they are still weak acids, only about several percent dissociate under normal conditions. They react and thus dissolve in solutions of sodium hydroxide, sodium carbonate and sodium hydrogencarbonate.
RCOOH + NaOH RCOO-Na+ + H2O 2RCOOH + Na2CO3 2 RCOO-Na+ + H2O + CO2 RCOOH + NaHCO3 RCOO-Na+ + H2O + CO2

Phenols are slightly acidic, it can react with and thus dissolve in aqueous NaOH with the formation of
water.

OH + NaOH

O-Na+ + H2O

However, phenols are not acidic enough to react with and thus dissolve in solution of sodium carbonate or sodium hydrogencarbonate. No carbon dioxide is produced. This enables phenols to be differentiated from carboxylic acids.

OH + Na2CO3/NaHCO3

O-Na+ + H2O + CO2

Alcohols are essentially neutral, they do not react with NaOH, Na2CO3 or NaHCO3. They only react with those very reactive metals like sodium to give hydrogen.
2ROH + Na 2RO-Na+ + H2 In general, acidity of organic compounds :

carboxylic acid > phenols > alcohols

Acidity and its effect on chemical properties Carboxylic acids : react with and dissolve in NaOH, NaHCO3 and Na2CO3 Phenols : react with and dissolve in NaOH, do not react nor dissolve in NaHCO3 and Na2CO3 Alcohols : do not react with nor dissolve in NaOH, NaHCO3 and Na2CO3 Effect on blue litmus paper
Phenols and carboxylic acids can turn wet blue litmus paper red while alcohols have no effect.

Chemistry/Organic Acids & Organic Bases

1.4.2

Reasons for Acidity O

O R C O - + H 3 O+
+ O- + H 3 O

H + H2O O H + H2O
R

H + H 2O

+ O- + H 3 O

The presence of the carbonyl group attached to the -OH group increases acidity by two factors. 1. The carbonyl group is inductively electron withdrawing/donating, and this effect is inductively transmitted to the O-H bond. This leads to bond electrons at O-H closer to/further away from oxygen and thus strengthening/weakening the O-H bond in carboxylic acid. 2. In carboxylic acid, the conjugate base is the carboxylate ion RCOO-, with both O undergo sp2 hybridization. This enables extended delocalization of electron to disperse the negative charge throughout both oxygen atoms. Thus the carboxylate ion is extra-stabilized and carboxylic acid is a much stronger acid.

p orbital of C singly occupied

p orbital of O singly occupied

R
-

Extended delocalization of electron in RCOO

p orbital of O doubly occupied (i.e. lone pair)


Such extended delocalization of electron stabilization in carboxylate ion is much stronger than that in phenoxide ion. In phenoxide ion, the extended delocalization of electron to disperse the negative charge involves carbon

Reason :

atoms,

In carboxylate ion, extended delocalization of electron to disperse the negative charge involves oxygen

atoms,

Since electronegativity of oxygen is much greater than carbon, oxygen is much better/poorer to accommodate the negative charge the extended delocalization of electron effect is much stronger in carboxylate ion carboxylic acid is a much stronger acid than phenol

Chemistry/Organic Acids & Organic Bases

1.4.3 Effect of Substituents on Acidity of Carboxylic Acids 1.4.3.1 Effect of Halogen Halogen atoms are more electronegative than carbon atoms and are inductively electronwithdrawing/donating. Presence of halogen helps to disperse the negative charge on conjugate base stabilizes conjugate base shifts equilibrium to right stronger acid Examples
CH3CO2H FCH2CO2H ClCH2CO2H BrCH2CO2H ICH2CO2H Ka (mol dm-3) at 25oC 1.8 x 10-5 2.6 x 10-3 1.4 x 10-3 1.3 x 10-3 6.7 x 10-4

1.4.3.2 Effect of Site of Substituent The inductive electron-withdrawing effect of halogen can be transmitted through covalent bonds. However, such effect diminishes rapidly away from the site of carboxylate group.
The further the halogen is away from the carboxylate group the larger/smaller the stabilization effect on the conjugate base stronger/weaker acid

Examples

Ka (mol dm-3) at 25oC

CH3 CH2 CH2 COOH CH3 CH2 CH COOH Cl CH3 CH CH2 COOH

1.5 x 10-5 1.4 x 10-3 8.9 x 10-5

Cl CH2 CH2 CH2 COOH Cl

3.0 x 10-5

1.4.3.3 No. of Halogen Atoms The inductive effect of is additive and thus the more halogen atoms the larger/smaller the stabilization effect on conjugate base stronger/weaker acid Examples
CH3CO2H ClCH2CO2H Cl2CHCO2H Cl3CCO2H Ka (mol dm-3) at 25oC 1.8 x 10-5 1.4 x 10-3 5.5 x 10-2 2.3 x 10-1

Chemistry/Organic Acids & Organic Bases

Exercise : 1. Several Ka for carboxylic acids are given (i) methanoic acid and ethanoic acid. (ii) ethanoic acid and benzoic acid. HCO2H CH3CO2H C6H5CO2H

below. Explain the difference between 1.8 x 10-4 1.8 x 10-5 6.3 x 10-5

2. 2-hydroxybenzoic acid (pKa 2.98) is a stronger acid than 4-hydroxybenzoic acid (pKa 4.60). Why is that ?

Chemistry/Organic Acids & Organic Bases

1.4.4

Carboxylic acids react with reactive metals (e.g. magnesium, sodium), metal hydroxides, metal carbonates and metal hydrogencarbonates similar to common mineral acids. RCOOH + Na2CO3 RCOOH + NaHCO3 RCOOH + NaOH RCOOH + Na

Formation of Salt

Examples :

COOH + NaHCO3

COO-Na+ + H2O + CO2 sodium benzoate

2CH3COOH + Na2CO3 2CH3COO-Na+ + H2O + CO2 sodium ethanoate The name of a salt of a carboxylic acid consists of the name of the cation followed by the name of the acid with the ending -ic acid changed to -ate.

Salts are typical ionic compounds that are soluble in water but practical insoluble in organic solvents. Salts of carboxylic acids are crystalline non-volatile solids.

Chemistry/Organic Acids & Organic Bases

1.5 Acidity of Terminal Hydrogen in Alkane, Alkene and Alkyne Alkane, alkene and alkyne are extremely weak acids.

Their acidic properties are only shown in the presence of extremely strong bases. However, their pKa are quite different, alkynes are much more acidic than alkenes and alkanes.

H H C H
H C H
H
Reason :

H C H
H + H2O C H
C H + H2O H

H H + H2O H C H
H C

H C H + H3O+
pKa = 50

H C H
C

+ H3O+
pKa = 44

+ H3O+

pKa = 25

H3O+ + AFor an acid dissociation process HA + H2O the extent of dissociation depends on the relative stability of HA and A-. The more stable A- is compared to HA, the more favourable the dissociation is, i.e. stronger acid. Since alkane, alkene and alkyne are much more stable than their anions, the extent of dissociation depends on the relative stability of the three anions. Comparing the three anions, the lone pair is in sp, sp2 and sp3 for alkane, alkene and alkyne respectively. As s orbital is closer to nucleus s orbital is more/less stable than p orbital hybrid orbital with higher s character will be more/less stable stability of anions : HCC:- >/< CH2=CH:- >/< CH3-CH2:: HCCH >/< CH2=CH2 >/< CH3-CH3 acidity

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2. Separation Scheme Using Solubility Properties Except for lower member (less than 6 carbons), which are soluble in both water and organic solvents, carboxylic acids and their alkali salts show exactly opposite solubility behaviour. Because of the ready interconversion of acids and their salts, this difference in solubility behaviour is very useful for separation.

OH RCOOH acid insoluble in water (for large R) H


+

RCOO salt

soluble in water

We can separate a carboxylic acid from non-acidic compounds by taking advantage of its solubility and their insolubility in aqueous base; once the separation has been accompanied, we can regenerate the acid by acidification of the aqueous solution. For solids, we simply stir the mixture with aqueous base and then filter the solution from the insoluble, nonacidic materials; addition of mineral acid to the filtrate precipitates the carboxylic acid, which can be collected on a filter. A drying agent like MgSO4 may be used to dry the carboxylic acid. For liquids, we shake the mixture with aqueous base in a separating funnel and separate the aqueous layer from the insoluble organic layer; addition of acid to the aqueous layer again liberates the carboxylic acid, which can then be separated from the water. For completeness of separation and ease of handling, ether is usually added in which carboxylic acid is more soluble. Drying agent like MgSO4 is then added to the ether extract to remove trace of water. Finally the volatile ether is easily removed by distillation from the comparatively high-boiling acid.

Examples : 1. Oxidation of an alkylbenzene to carboxylic acid The unreacted starting material can be separated by adding aqueous base which takes away the carboxylic acid in the aqueous layer; carboxylic acid is then regenerated by addition of a mineral acid.
2. Oxidation of primary alcohol to carboxylic acid The reaction mixture contains the starting material primary the intermediate alcohol, aldehyde and the product carboxylic acid.

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Exercise : A mixture of benzoic acid, phenol and cyclohexanol is to be separated to give the isolated compounds. Describe the procedure to be used.

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3. Basicity

3.1 Basic Strength

Basic strength is the measure of the extent of the following equilibrium :

B + H 2O
Basic strength is measured by Kb =

HB+ + OH-

[ HB ][ OH ] . [B ]

Basic strength depends on two factors : 1. The availability of lone pair of electrons on B 2. The relative stability between the base and its conjugate acid

3.2 Basic Properties in Amines 3.2.1 Introduction Amines are organic derivatives of ammonia, formed by substitution of hydrogen atoms with alkyl groups. It is further divided into 4 classes, according to the number of alkyl groups attached to nitrogen atom.

H H N H H N H

H ammonia R1 N H R1 N H R1

H ammonium ion R4 N R3 R1 N R3

H primary amine
3.2.2 Basic Properties

R2 secondary amine

R2 tertiary amine

R2 quaternary ammonium ion

The lone pair of electrons on amines enables them to accept a proton and thus act as bases. They are relatively weak bases, much weaker than hydroxide ion.

They can turn red litmus paper blue. They react readily with acids to give salts. Examples :

H CH3CH2 N H H + HCl CH3CH2 N H H Cl

ethylammonium chloride

NH2 + HCl

NH3 Cl

phenylammonium chloride These ammonium salts are named by specifying the names of the alkyl groups attached to nitrogen as prefixes followed by ammonium, the name of the anion is given as the second word. Ammonium salts are typical ionic compounds. They are non-volatile solids; soluble in water, but insoluble in organic solvents.

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3.2.2.1 Amines vs Alcohols Amines are much more basic than alcohols. H

+ H+

H + H+

H Reason : N is less/more electronegative than O N can accommodate the positive charge to a better/poorer extent than O the conjugate acid for amine is stabilized/destabilized with respect to that of alcohol amines are stronger base than alcohols
NH3 CH3NH2 CH3CH2NH2 CH3CH2CH2NH2

Values of pKb
4.8 3.4 3.3 3.3

NH2
9.4

3.2.2.2 NH3 vs Primary Aliphatic Amines RNH2 H

N H

H + H2O

N H H

H +OH

N H

H + H2O

N H

H +OH

Since R groups are electron-donating/withdrawing, it increases/decreases the availability of lone pair of electrons at N; also it stabilizes/destabilizes the conjugate acid by dispersing/intensifying the positive charge primary amine is more/less basic than ammonia

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3.2.2.3 NH3 vs Phenylamine

H NH2 + H2O N H sp3 hybridized no delocalization thus no stabilization H +OH

sp2 hybridized lone pair delocalized with benzene ring

Since in phenylamine, its lone pair at N overlaps extensively with the p orbitals in benzene ring 1. Availability of lone pair of electrons is increased/decreased; also 2. In the conjugate base, the nitrogen atom has changed into sp3 hybridization can/cannot delocalize with the benzene stabilization in base but no stabilization in conjugate acid phenylamine is less/more basic than NH3

Question :

What would you expect the basicity of acid amide RCONH2, compared to RNH2 ?

O R C N H H R N H H

1. C=O group is electron withdrawing/donating and makes lone pair less/more available for donation; also 2. Lone pair in acid amide can/cannot undergo extended delocalization of electron to C=O and thus availability of electron is further increased/decreased Acid amide is less basic than primary amine because

Example : Arrange the following compounds in the order of increasing basic strength. Explain your arrangement.

NH2 NH2 , and NH3


(3 marks, 96, I, 3b)

Soln :

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3.2.2.4 Solubility The solubility properties of amines and their salts are useful in separating amines from non-basic compounds that are insoluble in water.

H R N H H+ R N R' H OHR H R N H H N R' H R N R' R" R N R' R" H soluble in water H

insoluble in water for large R

The amine can be extracted into aqueous acid (dil. HCl) and then recovered by making the aqueous solution basic and extracting the amine into ether. Ether is then distilled away.

Exercise : Devise a schematic scheme for the separation and isolation of a mixture of cyclohexanol, phenol, benzoic acid and phenylamine.

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4. Amino Acids Amino acids are organic compounds with amino group and carboxylic acid group in the same molecule.

R H C COOH

NH2 4.1 Physical Properties The presence of acidic and basic group in amino acid leads to special physical properties.
The acidic group and the basic group interact with each other to give an internal salt, which is a dipolar ion commonly known as a zwitterion. forces between particles are exceptional strong/weak

R H2N C H accepts H+
4.1.1 Melting point

R COOH H3N C H loses H+ dipolar ion (zwitterion) COO

Ionic bond between zwitterions in solid amino acids have exceptionally high/low melting point they are white crystalline solids at room conditions Dipolar ions present in amino acids strong/weak interaction between the dipolar ions and water amino acids have high/low solubility in water and are generally soluble/insoluble in common

4.1.2

Solubility

organic solvents

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4.2 Chemical Properties In aqueous solution, the acidic and basic properties of amino acid are shown by the equilibrium among the dipolar ion, the anionic and the cationic forms of an amino acid.

H H3N C R cationic form (predominant in strong acidic condition) COOH

H -H +H H3N C R dipolar ion (zwitterion) COO -H +H H2N

H C R anionic form (predominant in strong basic condition) COO

The predominant form of the amino acid present in a solution depends on the pH of the solution. In strongly acidic solutions (very low pH), H+ is added/removed from the dipolar ion amino acids exist as cations/anions In strongly basic solutions (very high pH), H+ is added/removed from the dipolar ion amino acids exist as cations/anions

Isoelectric Point : At some intermediate pH, the concentration of the dipolar ion is at its maximum and the concentrations of the anions and cations are equal. Such pH is called the isoelectric point. Each amino acid has a specific isoelectric point. Exceptionally weak acid & weak base : Amino acid itself is very weak acid and very weak base, much weaker than carboxylic acid and amine respectively. Reason : The presence of both acidic group (carboxylic acid) and basic group (amine) in amino acid means internal neutralization is possible. This leads to much weaker acidic group and basic group. From the above equilibria, since amino acid exist as dipolar ion, 1. the acidic properties of amino acid is not due to the much stronger -COOH group but to the much weaker -NH3+ group & 2. the basic properties of amino acid is not due to the much stronger NH2 group but to the much weaker -COO- group, amino acids are exceptionally weak acids & weak bases 4.2.1
4.2.1.1 With Alkali, e.g. NaOH

Salt Formation

R H 2N C H
4.2.1.2 With Acid, e.g. HCl

COOH + NaOH

R H 2N C H COOH + HCl

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4.2.2

4.2.2.1 Dipeptide Dipeptide is the condensation product when two amino acids link together. The two amino acids may be the same or different.

Peptide formation

R H 2N C H

O C OH H N H

R C H COOH H 2N

R C H

O C N H

R C H COOH + H 2O

dipeptide
This is just the formation of acid amide. It can also be considered as a condensation reaction. The linkage is commonly known as the peptide bond or peptide linkage.

O C N H
Example : A dipeptide, upon acid-catalysed hydrolysis, gives two amino acids, J and L.

CH2 CH COOH
CH3 CH COOH NH2
(i) What are the possible structures of the dipeptide ? (ii) Given that the isoelectric point of the amino-acid J is 6.0, what form of J would you expect to predominant at pH 1, pH 6, and pH 14 respectively ? (4 marks, 89, II, 8c)

NH2 L

Soln :

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Further condensation of amino acids gives a polymer of amino acid, known as polypeptide. The sequence of the amino acids that are linked in polypeptide determines its properties. Polypeptide usually refers to polymer with less than 50 amino acids. Protein refers to polymer with more than 50 amino acids.

4.2.2.2 Polypeptides

R n H N H C H

O C OH H2N

R C H

O C N H

R C H n-1 COOH + (n-1) H2O

polypeptide
By convention, the peptide structure is written with the N-terminal on the left and the C-terminal on the right. Polypeptides are hydrolyzed to amino acids. The reaction is usually carried out in acidic medium under reflux for a day.

4.2.3

Hydrolysis of Polypeptides

R H2N C H

O C N H

R C H n-1 COOH + (n-1) H2O

H+ n H reflux H N

R C H

O C OH

The amino acids obtained after hydrolysis can be identified using paper chromatography. Known amino acids are used as standards. Ninhydrin (a dye) is used to make amino acids visible in the chromatogram.

Exercise :

CO2H CH3 C H V NH2

Give the structure of the compound with a relative molecular mass of approximately 230, which on refluxing with dilute hydrochloric acid gives V as the only product. (Relative atomic masses : H : 1.0; C : 12.0; N : 14.0; O : 16.0) (2 marks, 92, I, 1f)

Soln :

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