Relative Reactivities of Aldehydes and Ketones

Introduction

It might be due to the positive charge on the Carbon that aldehydes and ketones exhibit different reactivity in nucleophilic addition reactions. Positive charges seem to exhibit a higher reactivity. The carbonyl compound becomes more stable and less reactive when the positive charge is detached from the molecule. Rather, we have an alkyl group that releases electrons (+I inductive effect). 

Two alkyl groups release much more electrons than one alkyl group in aldehydes, therefore two alkyl groups in ketones are more energetically active. In ketones the Carbon atom of carbonyl group is not available as much as it is available in aldehydes. As a result, the substitution of positive charge on Carbon makes ketones more resistant to nucleophilic attack. Ketones, therefore, are less reactive than aldehydes. In terms of aldehydes and ketones, formaldehyde is the most reactive. So, the list runs:

Nucleophiles are prevented from easily approaching the electrophilic site on the carbonyl because crowding prevents them from approaching the electron-rich site.  The nucleophile will likely bounce off anything but the carbonyl carbon if it hits something else.  In order for electrons to be delivered to the right place, it needs to collide with the carbonyl Carbon.

An electrophile will react more readily if it is positively charged.

In the presence of positive-charged groups close to the carbonyl, the carbonyl becomes more positive and reactive. Carbonyls are less reactive when they have more electron density (electron donors nearby).

Reversible Addition Reactions

A. Hydration and Hemiacetal Formation

In most cases, the hydrate formed when water reacts rapidly with aldehydes or ketones (a geminal-diol) is unstable compared to the reactants and cannot be isolated. A common exception to this rule is formaldehyde (a gas in its pure monomeric form). Because the carbonyl double bond has a weaker pi component than other aldehyde ketone, and because the hydrogen substituents are small, addition is more likely. Therefore, the hydrate or polymers of formaldehyde are present in almost all solutions of formaldehyde in water (formalin). Aldehydes and ketones also react reversibly with alcohols. They give rise to hemiacetals, which are equally unstable.

R2C=O   +   R’OH      R’O–(R2)C–O–H   (a hemiacetal)

B. Acetal Formation

By reacting two equivalents of an alcohol with an ketone aldehyde, and removing the water, acetals are formed. Check out the following equation for the conversion of aldehydes and ketones to acetals- 

R2C=O   +   2 R’OH   →   R2C(OR’)2   +   H2O   (an acetal)

Aldehydes and ketones react with highly nucleophilic aryl, metallohydride, and alkyl reagents . This is one of their most useful and characteristic properties. Acetals are excellent protective groups when it comes to preventing irreversible addition reactions when the carbonyl functional group is converted to an acetal.

1. Formation of Imines and Related Compounds

Schiff bases (compounds with the C=N function) are imine derivatives formed when aldehydes and ketones are combined with ammonia or primary amine. This reaction is critical to synthesising 2o-amines. As with acetal formation, this acid-catalyzed reaction eliminates water.

R2C=O   +   R’NH2   →   R’NH–(R2)C–O–H      R2C=NR’   +   H2O

D. Enamine Formation

Enamines formed by combining aldehydes and ketones with amines. Below diagram shows the enamine formation similar to acetal formation. Water is lost in these acid-catalyzed reversible reactions. By converting enamines back to carbonyls through acid catalyzed hydrolysis, they are easily regenerated. 

E. Cyanohydrin Formation

Cyanide (HC≡N) can also be reversibly added to water to form products called cyanohydrins.

RCH=O   +   H–C≡N    →  RCH(OH)CN     (a cyanohydrin)

Due to the fact that hydrogen cyanide is itself an acid (pKa = 9.25), the addition cannot be acid-catalyzed. Whenever the cyanide anion, C≡N(-), is used, a catalytic base must be added. An aldehyde-friendly reaction, cyclic ketones and methyl ketones can form unhindered. 

Irreversible Addition Reactions

By comparing the stability of alcohols, it is possible to differentiate between irreversible and reversible carbonyl addition reactions.

The risk of the compound being unstable (not isolable) increases if the substituent Y is not a hydrogen, an alkyl group, or an aryl group. Hemiacetals and hydrates (Y = OH &OR), molecules spontaneously decompose into their carbonyl compounds. In the absence of dehydration conditions aminols (Y = NHR) revert to their carbonyl precursors. It is also impossible to isolate 𝞪-halo alcohols (Y = Cl, Br & I) since when the hydrogen atom is lost, they decompose immediately. Carbonyl groups are evidently reversible in all these cases where H-Y additions take place.

When substituent Y is a hydrogen, an alkyl group, or an aryl group, the alcohol is stable and does not decompose on heating with loss of hydrogen or hydrocarbons. The alcohol products of such additions are irreversible if nucleophilic reagents corresponding to H:(–), R:(–) or Ar:(–) are added to aldehydes and ketones. This type of anion would have excellent base and nucleophilic properties but would be extremely difficult to prepare and use due to its extraordinary reactivity. These alkyl, aryl, and hydride moiety derivatives can be added to carbonyl compounds.

A. Reduction by Complex Metal Hydrides

Aldehydes and ketones would be produced by adding hydride anion to them. On protonation, the alkoxide anion would yield the corresponding alcohol. As shown, aldehydes produce a primary alcohol and ketones produce a secondary alcohol.

RCH=O   +   H:(–)   →  RCH2O(–)   +   H3O(+) →     RCH2OH

Lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4) are two practical sources of hydride-like reactivity. Sodium hydrides and lithium hydrides are produced by reacting aluminum or boron halides with esters to produce white (or near white) solids. As the most reactive of the two compounds, lithium aluminum hydride reacts violently with water, alcohols, and other acids to produce hydrogen gas. The following table summarizes some important characteristics of these useful reagents.

Special Case 

A metal hydride reagent can sometimes reduce 𝞪,𝝱-unsaturated ketones to saturated alcohols, especially when combined with sodium borohydride. Firstly, an enol molecule is conjugated to a hydrogen atom (hydride), followed by enol ketonization and then reduction of the saturated ketone (equation 1 below). A catalytic hydrogenation may be required prior to (or following) the hydride reduction if the desired product is the saturated alcohol. It is normal to carry out the reaction below zero degrees Celsius, as shown in equation 2, to avoid reducing the double bond.

B. Addition of Organometallic Reagents

Alkyl lithium reagents and Grignard reagents are two of the most common compounds of this kind. Alkyl hydrogen and aryl hydrogen halides are used. Nucleophilic and very strong bases, we find that the alkoxide salts of lithium and magnesium are easily formed by reacting them with carbonyl carbon atoms. Epoxides undergo many carbonyl-like reactions due to their ring strains. Chemists can associate simple starting compounds to create more complex structures using reactions of this sort, because they are among the most important synthetic methods available.

Other Carbonyl Group Reactions

A. Reduction

When oxygen is completely removed from a carbonyl group to make the reductive conversion to methylene possible, it is called deoxygenation. A symbol of [H] is used in the shorthand equation to indicate unspecified reduction conditions that achieve the desired change. In this section, we describe three distinct methods for achieving this transformation.

R2C=O   +   [H] →     R2CH2   +   H2O

1. Wolff-Kishner Reduction

On heating with base, the corresponding hydrocarbon is produced by the reaction of an aldehyde or ketone with excess hydrazine. To achieve the temperatures required, diethylene glycol, a hot hydroxylic solvent, is commonly used. 

2. Clemmensen Reduction

In this alternative reduction, finely divided, amalgamated zinc is heated with a carbonyl compound. A natural mineral acid like HCl is added to an aqueous solution containing a hydroxylic solvent. Its function is only to create a clean active metal surface on which the mercury alloyed with the zinc can act.

3. Hydrogenolysis of Thioacetals

The carbonyl deoxygenation procedure described here requires two steps in contrast to the previous two procedures. This procedure, however, does not involve strong bases or acids. Aldehyde or ketone must first be converted into a thioacetal. It is then possible to isolate and purify these derivatives prior to further reductions. 

During the second step, the thioacetal solution is refluxed over a nickel catalyst, called Raney Nickel. The hydrogen is added to the C–S bonds causing them to break. Two carbonyl groups are present in this bicyclic compound, but one is sterically hindered. Thus, the less-hindered ketone may be readily converted into a mono-thioacetal, and this can be reduced without changing the remaining carbonyl function.

B. Oxidation

An carbonyl group contains at least one carbon atom that is oxidized. It is evident from the fact that many of the reactions described thus far have either no effect on the oxidized state (e.g. acetals and imines) or have a reduction effect (e.g. organometallic additions and deoxygenations). Aldehydes are commonly converted into carboxylic acids by oxidation. The [O] symbol indicates unspecified conditions of oxidation that will bring about the desired outcome. 

RCH=O   +   [O]   →   RC(OH)=O

Aldehydes will be oxidized slowly by air, most likely through a radical mechanism. As oxidizing agents (oxidants), Tollens’ test, Benedict’s test, and Fehling’s test are useful in identifying aldehydes because they take advantage of this ease of oxidation.

RCH=O   +   2 [Ag(+) OH(–)]   →   RC(OH)=O   +   2 Ag (metallic mirror)   +   H2O

A beautiful mirror forms on the inside surface of the reaction vessel when silver cation is the oxidant in the preceding equation. A cupric cation is used as the oxidant in Fehling and Benedict tests. A red to yellow solid precipitates as a result of the reduction of this deep blue reagent to cuprous oxide. Alkaline conditions are necessary for these cation oxidations. The cations must be stabilized as complexed ions in order to prevent precipitation of the insoluble metal hydroxides. Ag(NH3)2(+) is used for silver as its ammonia complex, while cupric ions act as solid citrates or tartrates.

Conclusion 

What mostly affects the reactiveness of aldehydes and ketones is the positive charge they carry. Crowded carbonyls inhibit nucleophiles from approaching the electrophilic carbonyl site, thereby affecting reactivity.  A nucleophile may bounce off anything except the carbonyl carbon if it comes into contact with it.  For its electrons to reach the right location, it needs to collide with the carbonyl carbon.

An electrophile will react more readily if it is positively charged.

Factors that cause the carbonyl to become more positive (electron withdrawing groups surrounding the carbonyl) exacerbate this reaction. The carbonyl will become less reactive when there are electron donors nearby that increase the electron density on the carbonyl.