33 - carboxylic acid and derivatives

production of benzoic acid

• Benzoic acid is the simplest aromatic carboxylic acids with the molecular formula of C₆H₅COOH

• Benzoic acid and its derivatives are often used as reagents in the synthesis of esters

• The compounds can be produced from the oxidation of alkylbenzenes

Oxidation of alkylbenzenes

• The alkyl side-chain in alkylbenzenes, such as methylbenzene, can be oxidised to a carboxylic acid

• The alkylbenzene is heated under reflux with a solution of hot alkaline KMnO₄ (this is the oxidising agent)

  • The purple colour of the Mn⁷⁺ ions disappears as they are reduced to Mn⁴⁺ions

  • A brown precipitate of MnO₂ is formed

• The mixture is then acidified with dilute acid (such as hydrochloric acid or sulfuric acid) to protonate the organic product form and produce a benzoic acid

Making benzoic acid from methylbenzene

Alkylbenzenes such as methylbenzene undergo oxidation to form benzoic acid

reactions of carboxylic acids to produce acyl chlorides

• Acyl chlorides are compounds with the functional group -COCl

• They look similar in structure to carboxylic acids but have a Cl atom instead of an -OH group attached to the carbonyl (C=O)

• Acyl chlorides are more reactive than their corresponding carboxylic acids and are therefore often used as starting materials in the production of organic compounds such as esters

• They can be prepared from the reaction of carboxylic acids with:

  • Solid phosphorus(V) chloride (PCl₅)

  • Liquid phosphorus(III) chloride (PCl₃) and heat

  • Liquid sulfur dichloride oxide (SOCl₂)

• For example, the acyl chloride ethanoyl chloride can be formed from ethanoic acid in the above reactions

Using ethanoic acid to form ethanoyl chloride

Ethanoic acid can be used to produce ethanoyl chloride with different by-products depending on the reagent used

further oxidation of carboxylic acids

• Carboxylic acids can be formed from the oxidation of primary alcohols

• The primary alcohols are firstly oxidised to aldehydes and then further oxidised to carboxylic acids

• Some carboxylic acids can get even further oxidised

Methanoic acid

• Methanoic acid is a strong reducing agent and gets further oxidised to carbon dioxide (CO₂)

• The oxidation of methanoic acid can occur by:

  • Warming methanoic acid with mild oxidising agents such as Fehling’s or Tollens’ reagent

    • In a Fehling’s solution, the Cu²⁺ ion is reduced to Cu⁺ ion which precipitates as red Cu₂O

    • With Tollens’ reagent, the Ag⁺ is reduced to Ag

  • Using stronger oxidising agents such as acidified KMnO₄ or acidified K₂Cr₂O₇

    • The purple KMnO₄ solution turns colourless as Mn⁷⁺ ions are reduced to Mn²⁺ ions

    • The orange K₂Cr₂O₇ solution turns green as the Cr⁶⁺ ions are reduced to Cr³⁺ ions

Ethanedioic acid

• Another carboxylic acid that can get further oxidised is ethanedioic acid

• A strong oxidising agent such as warm acidified KMnO₄ is required for the oxidation of ethanedioic acid to carbon dioxide

relative acidities of carboxylic acids, phenols and alcohols

• Carboxylic acids are compounds with a -COOH functional group

• They can act as acids and lose a proton (H⁺ ion) in an aqueous solution to form carboxylate salts and water

Carboxylic acids forming carboxylate salts

Carboxylic acids dissociate in aqueous solutions to form carboxylate salts and water

• However, carboxylic acids are only weak acids as the position of equilibrium lies well over to the left-hand side

• The pK_a values of carboxylic acids, phenols, and alcohols suggest that carboxylic acids are stronger acids than alcohols and phenols

  • The pK_a is a measure of the relative strength of a species as an acid

  • The smaller the pK_a value, the stronger the acid

Relative acidity of ethanol, phenol & carboxylic acids table

Acid	Dissociation	pKa at 25 oC
Ethanol	C2H5OH (aq)  C2H5O– (aq) + H+ (aq)	16
Phenol	C6H5OH (aq)  C6H5O– (aq) + H+ (aq)	10
Ethanoic acid	CH3COOH (aq)  CH3COO– (aq) + H+ (aq)	4.8
Benzoic acid	C6H5COOH (aq)  C6H5COO– (aq) + H+ (aq)	4.2

 

• This order of relative acidities can be explained by looking at the strength of the O-H bond and the stability of the conjugate bases of the acids

explaining the relative acidities of carboxylic acids, phenols and alcohols by looking at the strength of the O-H bond

• In carboxylic acids, the electrons in the O-H bond are drawn towards the C-O bond

• The electrons in the C-O bond are drawn towards the C=O bond

• Overall, the O-H bond is weakened due to the carbonyl (C=O) group removing electron density from it and drawing it towards itself

• Carboxylic acids can therefore more easily lose a proton compared to phenols and alcohols which lack this electron-withdrawing carbonyl group

Comparing OH bond strength of carboxylic acids, ethanol and phenol

The carbonyl group in carboxylic acids draws the electrons away from the O-H bond causing it to become weaker compared to the O-H bond in phenols and alcohols

explaining the relative acidities of carboxylic acids, phenols and alcohols by looking at the stability of the conjugate bases of the acids : carboxylate ions

• The conjugate base of carboxylic acids is the carboxylate ion

• The charge density on the oxygen atom is spread out over the carboxylate ion

• This is because the charge is delocalised on an electronegative carbonyl oxygen atom

• As a result, the electrons on the oxygen atom are less available for bond formation with an H⁺ ion to reform the undissociated acid molecule with -COOH group

• The position of the dissociation equilibrium lies more to the right compared to alcohols and phenols

The equilibrium position of a carboxylic acid and its carboxylate ion

The carboxylate ion is stable due to the delocalisation of the charge density on the electronegative oxygen

explaining the relative acidities of carboxylic acids, phenols and alcohols by looking at the stability of the conjugate bases of the acids : alkoxide ions

• The conjugate base of alcohols is the alkoxide ion

• The alkyl group in the ion is an electron-donating group that donates electron density to the oxygen atom

• As a result, the electron density on the oxygen atom is more readily available for bond formation with an H⁺ ion

• Alkoxide ions also lack the ability to delocalise the charge density on the entire ion

• The conjugate bases of alcohols are therefore less stable than the alcohols themselves and are more likely to reform the alcohol

• This means that alcohols are weaker acids compared to carboxylic acids and phenols

• The position of the dissociation equilibrium lies more to the left

The equilibrium position of an alcohol and its alkoxide ion

The electron-donating alkyl groups in alkoxide ions increase the electron density on the oxygen atom which is, therefore, more likely to bond with a H⁺ ion and reform the alcohol

explaining the relative acidities of carboxylic acids, phenols and alcohols by looking at the stability of the conjugate bases of the acids : phenoxide ions

• In the phenoxide ion (which is the conjugate base of phenol) the charge density on the oxygen atom is spread out over the entire ion

  • This delocalisation of electrons stabilises the phenoxide ion

• As a result, the electrons on the oxygen atom are less available for bond formation with a proton (H⁺ ion)

• The conjugate base of phenols is therefore more stable than phenol

• However, since the delocalisation of charge density is on carbon atoms and not on electronegative oxygen atoms like in the carboxylate ion, phenoxide ions are less stable than carboxylate ions

• Therefore, phenols are weaker acids relative to carboxylic acids

• The position of the dissociation equilibrium lies more to the right compared to alcohols and more to the left compared to carboxylic acids

The equilibrium position of phenol and the phenoxide ion

The charge density is delocalised on the entire benzene ring in the phenoxide ions

relative acidities of chlorine - substituted carboxylic acids overview

• Electron-withdrawing groups bonded to the carbon attached to the -COOH group make the carboxylic acids stronger acids

• This is because the O-H bond in the undissociated acid molecule is even further weakened as the electron-withdrawing group draws even more electron density away from this bond

• Furthermore, the electron-withdrawing groups extend the delocalisation of the negative charge on the -COO^- group of the carboxylate ion

• The -COO^- group is now even more stabilised and is less likely to bond with an H⁺ion

• Chlorine-substituted carboxylic acids are examples of carboxylic acids with electron-withdrawing groups

pK_avalues of ethanoic acid and chlorine-substituted derivatives table

Acid	pKa at 25 oC
Ethanoic acid, CH3COOH	4.8
Chloroethanoic acid, CH2ClCOOH	2.9
Dichloroethanoic acid, CHCl2COOH	1.3
Trichloroethanoic acid, CCl3COOH	0.6

• The pK_a values of ethanoic acid and chloro-substituted derivatives show that the more electron-withdrawing groups there are on the carbon attached to the -COOH group, the stronger the acid

Comparing the relative acidities of chlorine substituted derivatives of ethanoic acid

• Trichloroethanoic acid is the strongest acid as:

  • The O-H bond in CCl₃COOH is the weakest since there are three very strong electronegative Cl atoms withdrawing electron density from the -COOH group

  • When the O-H is broken to form the carboxylate (-COO^-) ion, the charge density is further spread out by the three electron-withdrawing Cl atoms

  • The carboxylate ion is so stabilised that it is less attracted to H⁺ ions

The equilibrium of trichloroethanoic acid and the trichloroethanoate ion

Relative acidity of trichloroethanoic acid

• Ethanoic acid is the weakest acid as:

  • It contains an electron-donating methyl group which strengthens the O-H bond

  • The methyl group donates negative charge towards the -COO^- group which becomes more likely to accept an H⁺ ion

The equilibrium of ethanoic acid and the ethanoate ion 

Relative acidity of ethanoic acid

Production of Esters by Reacting Alcohols With Acyl Chlorides

• Esters are organic compounds with an -COOR functional group

• They have characteristic smells and are used in perfumes, cosmetics and as solvents

• Esters can be prepared from the condensation reaction between alcohols and carboxylic acids

  • This is also called an esterification reaction

• A more effective way of preparing esters is from the condensation reaction between alcohols and acyl chlorides instead

• Unlike the reactions with carboxylic acids, acyl chlorides are more reactive (so the reactions happen faster) and their reactions go to completion (so no equilibrium mixture is formed and the yield of the ester is maximum)

• Examples of esterification reactions include:

  • Formation of ethyl ethanoate from ethanol and ethanoyl chloride

  • Formation of phenyl benzoate from phenol and benzoyl chloride

Formation of esters from the reaction of alcohols with acyl chlorides

The first part of the ester name comes from the alcohol and the second part of the ester name comes from the acyl chloride

production of acyl chlorides

• Due to the increased reactivity of acyl chlorides compared to carboxylic acids, they are often used as starting compounds in organic reactions

• Acyl chlorides are compounds that contain an -COCl functional group and can be prepared from the reaction of carboxylic acids with:

  • Solid phosphorus(V) chloride (PCl₅)

  • Liquid phosphorus(III) chloride (PCl₃) and heat

  • Liquid sulfur dichloride oxide (SOCl₂)

• Propanoyl chloride can this way be prepared from propanoic acid using the reactions above

Using propanoic acid to form propanoyl chloride

Propanoic acid can be used to produce propanoyl chloride with different by-products depending on the reagent used

overview of the reactions of acyl chlorides

• Acyl chlorides are reactive organic compounds that undergo many reactions such as addition-elimination reactions

• In addition-elimination reactions, the addition of a small molecule across the C=O bond takes place followed by elimination of a small molecule

• Examples of these addition-elimination reactions include:

  • Hydrolysis

  • Reaction with alcohols and phenols to form esters

  • Reaction with ammonia and amines to form amides

hydrolysis of acyl chlorides

• The hydrolysis of acyl chlorides results in the formation of a carboxylic acid and HCl molecule

• This is an addition-elimination reaction

  • A water molecule adds across the C=O bond

  • A hydrochloric acid (HCl) molecule is eliminated (hydrogen chloride gas but it is dissolved in solution)

• An example is the hydrolysis of propanoyl chloride to form propanoic acid and HCl

Hydrolysis of acyl chlorides

Acyl chlorides are hydrolysed to carboxylic acids

formation of esters with acyl chlorides

• Acyl chlorides can react with alcohols and phenols to form esters

  • The reaction with phenols requires heat and a base

• Esters can also be formed from the reaction of carboxylic acids with phenol and alcohols however, this is a slower reaction as carboxylic acids are less reactive and the reaction does not go to completion (so less product is formed)

• Acyl chlorides are therefore more useful in the synthesis of esters

• The esterification of acyl chlorides is also an addition-elimination reaction

  • The alcohol or phenol adds across the C=O bond

  • A HCl molecule is eliminated

Esterification reactions using acyl chlorides

Acyl chlorides undergo esterification with alcohols and phenols to form esters

formation of amides

• Acyl chlorides react with ammonia or primary amines to form amides in a condensation reaction.

• A lone pair on the nitrogen atom attacks the carbonyl carbon in the acyl chloride.

• The reaction proceeds via a nucleophilic addition–elimination mechanism:

  • The nucleophile adds to the C=O bond

  • A chloride ion (Cl⁻) is eliminated

  • Hydrogen chloride (HCl) is formed

What happens to the HCl?

• The HCl formed does not remain unreacted.

• It is immediately neutralised by a second molecule of ammonia or amine present in excess.

• This forms an ammonium salt (e.g. NH₄Cl, CH₃NH₃Cl).

Why 2 molecules are needed

• The 1st molecule of ammonia/amine forms the amide

• The 2nd molecule of ammonia/amine neutralises the HCl and forms ammonium salt

Examples

• Reaction with ammonia

• Product: Primary amide (propanamide) and ammonium chloride

CH₃CH₂COCl + 2NH₃ → CH₃CH₂CONH₂ + NH₄Cl

• Reaction with methylamine

• Product: Secondary (substituted) amide and methylammonium chloride

CH₃COCl + 2CH₃NH₂ → CH₃CONHCH₃ + CH₃NH₃Cl

• Reaction with ethylamine

• Product: Secondary (substituted) amide and ethylammonium chloride

CH₃COCl + 2CH₃CH₂NH₂ → CH₃CONHCH₂CH₃ + CH₃CH₂NH₃Cl

Summary for formation of amides

• All reactions form HCl, which is not observed as a separate product

• The HCl is neutralised by excess ammonia or amine

• The final products are an amide and an ammonium salt

addition elimination in acyl chloride reactions mechanism

• Acyl chlorides undergo addition-elimination reactions such as hydrolysis, esterification reactions to form esters, and condensation reactions to form amides

• The general mechanism of these addition-elimination reactions involves two steps:

  • Step 1 - Addition of a nucleophile across the C=O bond

  • Step 2 - Elimination of a small molecule such as HCl or H₂O

mechanism of hydrolysis of acyl chlorides

• In the hydrolysis of acyl chlorides, the water molecule acts as a nucleophile

  • The lone pair of the oxygen atom from water carries out an initial attack on the carbonyl carbon

  • This is followed by the elimination of a hydrochloric acid (HCl) molecule

Reaction mechanism of the hydrolysis of acyl chlorides 

The two-step addition-elimination reaction mechanism of propanoyl chloride to form propanoic acid

mechanism for formation of esters with acyl chlorides

• In the esterification reaction of acyl chlorides, the alcohols or phenols act as a nucleophile

  • The lone pair of the alcohol / phenol oxygen atom carries out an initial attack on the carbonyl carbon

  • This is again followed by the elimination of an HCl molecule

• With phenols, the reaction requires heat to proceed and needs to be carried out in the presence of a base

• The base deprotonates the phenol to form a phenoxide ion which is a better nucleophile than the phenol molecule

  • The phenoxide ion carries out an initial attack on the carbonyl carbon

  • A small molecule of NaCl is eliminated

Reaction mechanism of the esterification of acyl chlorides with alcohols

The two-step addition-elimination reaction mechanism of propanoyl chloride and ethanol to form ethyl propanoate and water

Reaction mechanism of the esterification of acyl chlorides with phenols

The three-step addition-elimination reaction mechanism of propanoyl chloride with phenol to form phenyl propanoate

mechanism for the formation of amides

• The nitrogen atom in ammonia and primary/secondary amines act as a nucleophile

  • The lone pair of the nitrogen atom carries out an initial attack on the carbonyl carbon

  • This is followed by the elimination of an HCl molecule

• Both reactions of acyl chlorides with ammonia and amines are vigorous however there are also differences

  • With ammonia - The product is a non-substituted amide and white fumes of HCl are formed

  • With amines - The product is a substituted amide and the HCl formed reacts with the unreacted amine to form a white organic ammonium salt

Reaction mechanism of the formation of amides from acyl chlorides with ammonia

The two-step addition-elimination reaction mechanism of propanoyl chloride and ammonia to form propanamide

Reaction mechanism of the formation of amides from acyl chlorides with primary amines

The addition-elimination reaction mechanism of propanoyl chloride and methylamine to form methylpropanamide

Reaction mechanism of the formation of amides from acyl chlorides with secondary amines

The addition-elimination reaction mechanism of propanoyl chloride and dimethylamine to form dimethylpropanamide

overview of the ease of hydrolysis for different organic compounds and how it can be explained

• Hydrolysis is the breakdown of a compound using water

• The ease of hydrolysis for different organic compounds may differ

• For example, the ease of hydrolysis, starting with the compounds most readily broken down, is: acyl chloride > alkyl chloride > aryl chloride

• This trend can be explained by looking at the strength of the C-Cl

strength of c-cl bond in acyl chlorides

• Acyl chlorides are hydrolysed most readily at room temperature

• This is because the carbon bonded to the chlorine atom is also attached to an oxygen atom

• There are two strong electronegative atoms pulling electrons away from the carbonyl carbon, leaving it very δ⁺

• The C-Cl bond is therefore weakened and nucleophilic attack of the carbonyl carbon is much more rapid

Hydrolysis of acyl chlorides

The hydrolysis of acyl chlorides occurs most readily

strength of the c-cl bond in alkyl chlorides

• The carbonyl carbon in alkyl chlorides is only attached to one electronegative atom which pulls electrons away from it

• This carbon atom is therefore not very δ⁺ and the C-Cl bond is stronger than the C-Cl bond in aryl chlorides

• The hydrolysis of alkyl chlorides, therefore, requires a strong alkali (such as OH^-) to be refluxed with it

• An OH^- ion will hydrolyse the alkyl chloride as it is a stronger nucleophile than H₂O

Hydrolysis of alkyl chlorides

The hydrolysis of alkyl chlorides requires a strong nucleophile

strength of the c-cl bond in aryl chlorides

• In aryl chlorides, the carbon atom bonded to the chlorine atom is part of the delocalised π bonding system of the benzene ring

• One of the lone pairs of electrons of the Cl atom overlaps with this delocalised system

• The C-Cl bond, therefore, has some double-bond character causing it to become stronger

• As a result, the C-Cl bond is difficult to break and hydrolysis will not occur

Hydrolysis of aryl chlorides

Due to the strong C-Cl bond in aryl chlorides, these compounds will not undergo hydrolysis