ORGANIC CHEMISTRY

Module 2. Alcohols, aldehydes and ketones

Lesson 5
REACTIONS OF ALDEHYDES AND KETONES

5.1 Introduction

Aldehydes and ketones are compounds of the following general formula (Fig. 5.1). Where R & R′ are alkyl or aryl groups. If R& R′ are same: Simple ketones. Different: mixed ketones.

• Both aldehydes and ketones contain the carbonyl (>C=O) group – therefore collectively termed as carbonyl compounds.

• This group largely determines the chemistry of aldehydes and ketones

• Aldehydes and ketones resemble each other closely in most of their properties

• However, in aldehydes a hydrogen atom is attached to carbonyl carbon, whereas, in ketones the two alkyl groups are attached to the carbonyl carbon.

• This difference in structure have two effects on their properties

1. Aldehydes are more susceptible to oxidation by mild oxidizing agents such as dil. H₂SO₄/ KMnO₄ or K₂Cr₂O₇ whereas ketones are oxidized only by drastic oxidizing agents such as conc. HNO₃ or H₂CrO₄.

2. Aldehydes are usually more reactive than ketones toward nucleophilic* addition, the characteristic reaction of carbonyl compounds

[*Nucleophile/Nucleophilic reagent (Nucleo = Nucleus, philes = loving/seeking/attaching].
An atomic or molecular species which can afford a pair of electrons for covalent-coordinate bond formation is called nucleophile. e.g. OH^- , halide ions, NH₃ ].

5.2 Structure of Carbonyl Group (Fig. 5.2)

• Carbonyl carbon is joined to three other atoms by σ bonds - since formation of these bonds utilizes sp2 orbital, these lie in a plane and 120° apart.

• The remaining p orbital of the carbon forms π bond with oxygen. Carbon and oxygen are joined by a double bond

• The part of the molecule immediately surrounding carbonyl carbon is flat - i.e. oxygen, carbonyl carbon and other two atoms directly attached to the carbonyl carbon lie in the same plane.

• The electronegativity of carbonyl carbon and the associated oxygen is quite different - hence electrons are strongly pulled towards more electronegative oxygen atom - therefore bond becomes polar.

5.2.1 Physical properties

1. Formaldehyde is gas at ordinary temperature, however, other aldehyde and ketones up to about C11 are colorless mobile liquids and the higher members are solids

2. Aldehydes possess an unpleasant pungent odour while ketones have a pleasant smell. However, the higer aldehydes possess fruity odour

3. The first few members of both series are fairly soluble in water – because of hydrogen bonding with water

4. Their boiling points are higher than those of alkanes of comparable molecular weight - because of polar nature

However, their boiling points are lower than those of alcohols from which they are made - because lack of hydrogen bond formation between their molecules = because they contain hydrogen bonded only to carbon ( and not with F, O or N).

5.2.2 Chemical reactions

>C=O = >C+- O-

• Carbonyl (>C=O) group governs the chemistry of aldehydes and ketones

• As discussed earlier carbonyl group is polar and flat

• Therefore, it is susceptible to unhindered attack from the above and below in a direction perpendicular to the carbonyl group

• It is highly reactive

• The reactions of carbonyl group generally involve formation of bond with the electron-deficient carbonyl carbon

• The carbonyl group is most susceptible to attack by electron-rich (nucleophilic) reagents e.g. CN-, SO3H+ etc.

• The reactions are mostly addition reactions - therefore called Nucleophilic addition reactions.

• Can be represented as shown below (Z= nucleophilic reagent or nucleophile) (Fig. 5.3)

• The nucleophilic reaction of carbonyl group is catalysed by acids

• Because they accentuate the electron-deficiency of the carbonyl carbon by combining with the electron-rich oxygen

• This prior protonation of carbonyl oxygen helps the movement of π electrons towards oxygen and lower the activation energy of >C=O group without having the oxygen atom to develop negative charge. (Fig. 5.4)

2.3 Relative reactivity of aldehydes and ketones

Aliphatic aldehydes and ketones are characterized by the following:

• Nucleophilic addition reactions in carbonyl compounds are controlled by two factors: steric and electronic.

• The carbonyl group is trigonal and in transition state it starts acquiring tetrahedral configuration in the reactions

• Thus the attached groups are brought closer together in transition state during nucleophilic addition reaction

• The quantum of steric hindrance in nucleophilic addition is in the following order: Methanal >Ethanal > Propanone-2> Butanone-2 > Pentanone-3 etc.

• The larger the ‘R’ and ‘R’ groups, the greater would be the resistance to accommodate them in the transition state of the reaction

• Ketones contain two alkyl or aryl groups, whereas, in aldehyde there is one alkyl or aryl group and one hydrogen atom.

• The second alkyl of aryl group of ketone is larger than the hydrogen of an aldehyde - therefore creates more steric hindrance

• Alkyl group attached to carbonyl carbon releases electrons (+I effect i.e. inductive effect) and thereby destabilize the transition state by intensifying the negative charge developing on carbonyl oxygen

• Aldehydes contain only one alkyl group, whereas ketones contain two alkyl groups – therefore the destabilizing effect resulting from a ketone would be greater than that of an aldehyde (steric factor and polarity of >C=O group).

• Aromatic aldehydes or ketones are characterized by the following:

• The electron-withdrawing effect (-I effect) of the aryl group (benzene ring) is expected to increase electron-deficiency at carbonyl carbon, thereby facilitating nucleophilic attack at the carbonyl carbon.

• However, electron releasing through resonance by the benzene ring (+R effect) decreases the electron-deficiency at carbonyl carbon.

• Consequently deactivate the carbonyl carbon towards nucleophilic attack.

• Resonance effect (+R) outweighs the inductive effect (-I); this causes net deactivation of carbonyl group in aromatic aldehyde/ketone towards nucleophilic attack.

1. Addition of sodium bisulphite

• Most aldehydes and many ketones (especially methyl ketones) form crystalline adduct with sodium bisulphite

Fig. 5.5 Adduct formation

• Addition of acid or alkali can destroy the bisulphite ion in equilibrium with the adduct and regenerate the carbonyl compound

Fig. 5.6 Regeneration of carbonyl compounds

• This reaction furnishes a method for purification and separation of suitable carbonyl compounds from non-carbonyl compounds

2. Addition of hydrogen cyanide

• Forms α-hydroxynitriles (cyanohydrins)

Fig. 5.7 Addition of HCN and hydrolysis of cyanohydrins

• Cyanohydrins can be easily hydrolysed into α-hydroxy acid. e.g.

Fig. 5.8 Hydrolysis of acetaldehyde cyanohydrins

3. Addition of Grignard reagents

• Ketones form tertiary alcohols upon hydrolysis of intermediate products. (Fig. 5.9)

• The reaction is useful

• In the synthesizing of series of organic compounds - because of formation of C-C bond

• For preparation of 1°, 2° and 3° alcohols

4. Addition of alcohol

• Aldehyde (but not ketone) forms acetal when treated with alcohol in presence of anhydrous acid. (Fig. 5.10)

• Dilute mineral acid decomposes acetal into the parent anhydride and alcohol even at ordinary temperature

• Therefore acetal formation is often used to protect aldehyde group, especially when to be treated with alkali- to avoid alkali induced condensation (polymerization)

5. Reaction with derivatives of ammonia (at pH = 3.5)

• Forms product containing carbon-nitrogen double bond – resulting from elimination of water molecule from an intermediate product. (Fig. 5.11) & (Fig. 5.12)

• The products are usually crystalline compounds with well-defined melting points- therefore very useful for characterization and identification of aldehydes and ketones

• The derivatives can be decomposed to regenerate the parent carbonyl compounds by boiling with dilute mineral acid- therefore used for purification of carbonyl compounds.

6. Aldol condensation

• Under influence of a dilute alkali two molecules of an aldehyde or ketone combine to form a β-hydroxy aldehyde or ketone

• This reaction is called aldol condensation

• In every case addition of one molecule or aldehyde (or ketone) to a second molecule occurs in such a way that the α-carbon of the first molecule gets attached to the carbonyl carbon of the second molecule (Fig. 5.13)

• Aldol condensation is possible only when the carbonyl compound contains atleast one α-hydrogen

• The compounds like formaldehyde, trimethylacetadehyde, aromatic aldehydes and diaryl ketones do not undergo aldol condensation

• Aldols still have acidic hydrogen - therefore aldol condensation may be repeated leading to formation of complex polymeric resinous product especially when strong alkali is used to induce aldol condensation

• Aldol condensation has a great synthetic potential

• β-hydroxycarbonyl compounds and α, β-unsaturated carbonyl compounds are usually synthesized via aldol condensation reactions

• From these unsaturated carbonyl compounds α, β-unsaturated alcohol is produced by reduction

• On catalytic hydrogenation saturated alcohol is obtained from the unsaturated alcohol - i.e. yields long chain saturated alcohol

7. Cannizzaro reaction

• In presence of concentrated alkali, aldehydes having no α-hydrogen undergo self oxidation-reduction to yield a mixture of an alcohol and a salt of a carboxylic acid (Fig. 5.14).

• Tertiary butyl aldehyde [(CH3)3CCHO] also undergoes cannizzaro reaction.

• A crossed cannizzaro reaction between an aromatic aldehyde and formaldehyde is an important synthetic reaction due to greater tendency of formaldehyde to undergo oxidation and gives almost exclusively the sodium formate and the alcohol corresponding to the aromatic aldehyde. (Fig. 5.15)

8. Perkin condensation

• Acid anhydries added to aromatic aldehydes in the presence of base to yield α,β-unsaturated acids.

• Reaction is called Perkin condensation and resembles aldol condensation.

• The base most commonly used is the sodium salt of carboxylic acid from which the anhydride is derived. (Fig. 5.16)

• By varying the substituent in the aromatic aldehyde, it is possible to make a wide variety of substituted cinnamic acids (C6H5CH=CHCOOH)- from which corresponding saturated acids may be obtained by hydrogenation.

 

9. Reduction to alcohol

• Aldehydes can be reduced to primary alcohols and ketones to secondary alcohols, either by catalytic hydrogenation or by use of chemical reducing agents like lithium aluminium hydride (LiAlH4). (Fig. 5.17 ) & (Fig. 5.18).

• Such reduction is useful for preparation of certain alcohols that are less available than the corresponding carbonyl compounds

 

10. Reduction to hydrocarbon

• Aldehydes and ketones can be reduced to hydrocarbon by

• Clemmensen Reduction – by action of amalgamated zinc and concentrated hydrochloric acid – for compounds sensitive to base

• Wolff-Kishner Reduction – by action of hydrazine (H2N-NH2) and a strong base like potassium hydroxide (KOH)- for compounds sensitive to acid

 

Fig. 5.19 Clemmensen and Wolff Kishner reductions

11. Oxidation

• Aldehydes are oxidized to acids containing same numbers of carbon atoms - even by a weak oxidizing agent e.g. KMnO4 or K2Cr2O7/ dil. H2SO4.

Fig. 5.20

• Oxidation of ketones requires the breaking of carbon-carbon bonds - therefore it occurs only under drastic conditions

Fig. 5.21 Oxidation of unsymmetrical ketones: Popoff’s Rule

• The extent with which aldehydes undergo oxidation is useful mainly for detecting these compounds and in particular for differentiating them from ketones

• Mild oxidizing agents used for this purpose are

1. Tollen’s Regents : ammonical solution of silver nitrate - Ag(NH₃)²⁺ ion
2. Fehling Solution : alkaline solution of cupric ion in presence of sodium potassium tartrate (Rochelle salt)- Cu(OH)₂
3. Benedict Solution : alkaline solution of cupric ion in presence of citrate - Cu(OH)₂

 

 

Fig. 5.22 Test for –CHO group

• The reaction is of value in synthesis of unsaturated acids from unsaturated aldehydes obtained from aldol condensation

• Where advantage is taken of the fact that the mild oxidizing agents (reagents) does not attack carbon-carbon double bonds. (Fig. 5.23)

 

12. Haloform reaction

• The oxidation reaction consists of treating a methyl ketone with sodium hypochlorite (hypohalite)= oxidises the ketones to acids containing one carbon atom less that the parent methyl ketone and haloform forms simultaneously. (Fig. 5.24)

• Iodoform test: used as a diagnostic test for methyl ketone is based on this reaction. (Fig. 5.25)