Carbonyl Compounds

Overview of Carbonyl Compounds

Carbonyl compounds are organic molecules that contain the carbonyl group, a carbon–oxygen double bond: $>\!C{=}O$. In this chapter we focus on the main classes where the carbonyl group is the central functional unit, with emphasis on their structures and typical reactions that follow from the special reactivity of $C{=}O$.

The most important simple carbonyl compound classes are:

• Aldehydes: $R{-}CHO$
• Ketones: $R{-}CO{-}R'$
• Carboxylic acid derivatives (introduced elsewhere, but often compared):
• Carboxylic acids: $R{-}COOH$
• Esters: $R{-}COOR'$
• Amides: $R{-}CONH_2$, $R{-}CONHR'$, $R{-}CONR'_2$
• Acid chlorides, anhydrides, etc.

Here we concentrate on aldehydes and ketones as “simple” carbonyl compounds, and on the general reactivity pattern of the $C{=}O$ group.

Structure and Bonding in the Carbonyl Group

Geometry and Hybridization

In a carbonyl group:

• The carbon atom is approximately $sp^2$-hybridized.
• The oxygen atom is also approximately $sp^2$-hybridized.
• The carbonyl carbon, the carbonyl oxygen, and the two atoms/groups attached to the carbon all lie in one plane (trigonal planar environment at the carbonyl carbon).
• The bond angles around the carbonyl carbon are close to $120^\circ$.

The $C{=}O$ double bond consists of:

• One $\sigma$-bond formed by overlap of $sp^2$ orbitals of C and O.
• One $\pi$-bond formed by overlap of unhybridized $p$ orbitals of C and O, perpendicular to the molecular plane.

Polarity of the Carbonyl Bond

Oxygen is more electronegative than carbon, so the $C{=}O$ bond is strongly polarized:

• Partial positive charge on carbon: $\delta^+$
• Partial negative charge on oxygen: $\delta^-$

This polarization leads to:

• Electrophilic character of the carbonyl carbon (site that can be attacked by nucleophiles).
• Nucleophilic/basic character of the carbonyl oxygen (can be protonated or coordinate to Lewis acids).

This combination underlies most of the characteristic reactions of carbonyl compounds.

Aldehydes and Ketones: Structures and Nomenclature

Basic Structural Difference

• Aldehydes: The carbonyl carbon is bonded to at least one hydrogen atom.
• General form: $R{-}CHO$
• Example: Ethanal, $CH_3CHO$
• Ketones: The carbonyl carbon is bonded to two carbon atoms.
• General form: $R{-}CO{-}R'$
• Example: Propanone (acetone), $CH_3COCH_3$

This structural difference has major consequences for both physical properties and reactivity, especially the relative reactivity of aldehydes vs. ketones.

Key Nomenclature Points (Specific to Carbonyls)

Nomenclature of organic compounds in general is handled elsewhere; here, only the rules specific to aldehydes and ketones are highlighted.

Aldehydes

For simple chain aldehydes:

• Replace the terminal -e of the parent alkane with -al.
• Methane → methanal
• Ethane → ethanal
• Propane → propanal
• The carbonyl carbon of an aldehyde is always at the end of the chain and is taken as carbon 1; in many simple names, the number is omitted (e.g. ethanal, not “ethan-1-al”).

For aromatic aldehydes:

• If the aldehyde group is directly attached to a benzene ring: benzaldehyde.
• Substituents on the ring are named as usual: e.g. 4-methylbenzaldehyde.

Ketones

For simple chain ketones:

• Replace the terminal -e of the parent alkane with -one.
• The position of the carbonyl group is indicated by a number (lowest possible).
• Propan-2-one (commonly: propanone, or acetone).
• Butan-2-one: $CH_3COCH_2CH_3$.
• In many simple cases, the locant is omitted when there is no ambiguity.

For more complex ketones:

• The carbon chain is numbered so that the carbonyl carbon gets the lowest possible number.
• If the ketone is not the highest-priority functional group, it may be named as an oxo-substituent (e.g. 3-oxobutanoic acid).

Physical Properties of Aldehydes and Ketones

Boiling and Melting Points

Key factors:

• The carbonyl group is polar, giving significant dipole–dipole interactions.
• Aldehydes and ketones cannot form hydrogen bonds to each other via the carbonyl oxygen as donors (they lack a $O{-}H$ or $N{-}H$ bond), though they can accept hydrogen bonds from other molecules (e.g. water, alcohols).

Consequences:

• Boiling points of aldehydes/ketones are higher than those of nonpolar hydrocarbons of similar molar mass (due to dipole–dipole interactions).
• Boiling points are lower than those of corresponding alcohols or carboxylic acids with similar molar mass (no self-association by hydrogen bonding).

Solubility in Water

• Low-molecular-mass aldehydes and ketones are typically miscible or well soluble in water.
• They can accept hydrogen bonds from water via the carbonyl oxygen.
• Solubility decreases with increasing length of the hydrophobic alkyl chains.

Odor and Volatility

Many simple aldehydes and ketones are volatile and have characteristic odors:

• Low-mass aldehydes (e.g. ethanal) have pungent, sharp smells.
• Many natural fragrances and flavor substances are aldehydes or ketones (e.g. vanillin, carvone).

Reactivity Pattern of the Carbonyl Group

Two main types of reactions are characteristic for carbonyl compounds:

1. Reactions at the carbonyl carbon (nucleophilic addition, or addition–elimination for derivatives).
2. Reactions at the $\alpha$-position (the carbon adjacent to the carbonyl carbon, $\alpha$-C), exploiting the acidity of $\alpha$-hydrogen atoms and the possibility of enol/enolate formation.

In this chapter we focus on aldehydes and ketones and the typical reactions at the carbonyl carbon; reactions of carboxylic acid derivatives and detailed $\alpha$-chemistry are treated elsewhere.

Electrophilic Carbonyl Carbon and Nucleophilic Addition

Because the carbonyl carbon is $\delta^+$, nucleophiles ($Nu^-$ or neutral electron-rich species) can attack it. A general schematic of nucleophilic addition to an aldehyde or ketone is:

1. Nucleophilic attack on the carbonyl carbon:
   $$R_2C{=}O + Nu^- \rightarrow R_2C(ONu)^-$$
2. Protonation of the resulting alkoxide:
   $$R_2C(ONu)^- + H^+ \rightarrow R_2C(OH)Nu$$

The product is usually called an “addition product”, often an alcohol derivative bearing the nucleophile.

In acidic conditions, the carbonyl group is often protonated first, which increases its electrophilicity:

1. Protonation:
   $$R_2C{=}O + H^+ \rightarrow R_2C(OH)^+$$
2. Nucleophilic attack by a neutral nucleophile $Nu$:
   $$R_2C(OH)^+ + Nu \rightarrow R_2C(OH)Nu^+$$
3. Deprotonation:
   $$R_2C(OH)Nu^+ \rightarrow R_2C(OH)Nu + H^+$$

The exact mechanism depends on the nucleophile and conditions, but the central idea remains: addition to the $C{=}O$.

Relative Reactivity: Aldehydes vs. Ketones

Aldehydes are generally more reactive than ketones in nucleophilic addition reactions. Two main reasons:

1. Electronic effect:
• Alkyl groups are weak electron donors by induction.
• In ketones, two alkyl groups reduce the positive character of the carbonyl carbon more than one alkyl group in aldehydes.
• Therefore, the carbonyl carbon in an aldehyde is more electrophilic.
2. Steric effect:
• In ketones, the carbonyl carbon is surrounded by two carbon groups, making approach by nucleophiles more hindered than in aldehydes (one carbon plus one hydrogen).

This difference in reactivity is often used in synthesis and in selective transformations.

Important Reactions of Aldehydes and Ketones

Nucleophilic Addition of Water: Hydrate (Gem-Diol) Formation

Aldehydes and ketones can react with water to form “hydrates” (geminal diols), especially under acid or base catalysis.

General reaction:

$$
R_2C{=}O + H_2O \rightleftharpoons R_2C(OH)_2
$$

• For many simple ketones, the equilibrium lies strongly on the side of the unhydrated carbonyl compound.
• Some aldehydes (especially highly electron-poor ones) can exist significantly as hydrates in water.

Mechanism (acid-catalyzed, simplified):

1. Protonation of the carbonyl oxygen.
2. Nucleophilic attack of water at the carbonyl carbon.
3. Deprotonation to give the diol.

Hydrate formation is fundamentally important in understanding many other addition reactions that follow the same pattern of nucleophile attack and proton transfer.

Nucleophilic Addition of Alcohols: Hemiacetals and Acetals

Reaction of an aldehyde or ketone with an alcohol $ROH$ can give:

• Hemiacetal or hemiketal (one $OR$ and one $OH$ attached to the same carbon).
• Acetal or ketal (two $OR$ groups attached to the same carbon, usually from two equivalents of alcohol, often via the hemiacetal).

For an aldehyde:

1. Hemiacetal formation:
   $$R{-}CHO + R'OH \rightleftharpoons R{-}CH(OH)OR'$$
2. Acetal formation (with additional alcohol under acidic conditions):
   $$R{-}CH(OH)OR' + R'OH \rightleftharpoons R{-}CH(OR')_2 + H_2O$$

Key points:

• Acid catalysis is typically required for efficient formation of acetals/ketals.
• Acetal formation is reversible and is an example of equilibrium chemistry.
• Acetals can be stable under basic conditions; they are widely used as protecting groups for carbonyl functions in organic synthesis.

Addition of Hydrogen Cyanide: Cyanohydrin Formation

Aldehydes and many ketones react with hydrogen cyanide $HCN$ (or equivalents such as $NaCN$ with a weak acid) to form cyanohydrins.

General reaction:

$$
R_2C{=}O + HCN \rightleftharpoons R_2C(OH)CN
$$

Mechanistic outline:

1. Generation of cyanide nucleophile:
   $$HCN \rightleftharpoons H^+ + CN^-$$
2. Nucleophilic attack of $CN^-$ on the carbonyl carbon, forming an alkoxide.
3. Protonation of the alkoxide by $HCN$ (or other proton source) to give the cyanohydrin.

Cyanohydrins are important intermediates because the nitrile group $-C{\equiv}N$ can be transformed into other functional groups (e.g. carboxylic acids, amines).

Addition of Amines: Imines, Enamines, and Related Products

Primary and secondary amines can add to carbonyl compounds under acid catalysis, giving various nitrogen-containing products.

Primary Amines → Imines (Schiff Bases)

With a primary amine $R'NH_2$, aldehydes and ketones can form imines ($C{=}N$ double bond).

Overall stoichiometry:

$$
R_2C{=}O + R'NH_2 \rightleftharpoons R_2C{=}NR' + H_2O
$$

Mechanistic outline (acid catalysis):

1. Nucleophilic addition of the amine to the protonated carbonyl to give a carbinolamine intermediate $R_2C(OH)NHR'$.
2. Dehydration (loss of water) to yield the imine.

Key aspects:

• An acid catalyst is needed but must be weak enough not to fully protonate the amine (otherwise it becomes non-nucleophilic).
• This is a reversible condensation reaction.

Secondary Amines → Enamines

Secondary amines $R'_2NH$ react with aldehydes/ketones to give enamines (alkenes conjugated to an amino group, $C{=}C{-}NR'_2$).

Overall:

$$
R_2C{=}O + R'_2NH \rightleftharpoons R_2C{=}C(NR'_2)H + H_2O
$$

The mechanism also passes through a carbinolamine intermediate, followed by dehydration, but the proton loss leads to formation of a $C{=}C$ bond rather than a $C{=}N$ double bond.

Imines and enamines are important intermediates in many carbonyl transformations and can be regarded as “masked” versions of aldehydes/ketones.

Reduction of Aldehydes and Ketones

Reduction to Alcohols

Aldehydes and ketones can be reduced to alcohols:

• Aldehydes → primary alcohols
  $$R{-}CHO \xrightarrow[\text{reductant}]{} R{-}CH_2OH$$
• Ketones → secondary alcohols
  $$R{-}CO{-}R' \xrightarrow[\text{reductant}]{} R{-}CHOH{-}R'$$

Common types of reductants (details covered elsewhere):

• Hydride donors (e.g. metal hydrides like NaBH$_4$, LiAlH$_4$).
• Catalytic hydrogenation with $H_2$ and a metal catalyst (e.g. Pd, Pt, Ni).

The mechanistic core is nucleophilic hydride addition to the carbonyl carbon, followed by protonation of the resulting alkoxide.

Reduction to Hydrocarbons

Under stronger reducing conditions or via specific multi-step sequences, aldehydes and ketones can be fully reduced to hydrocarbons. Examples include:

• Complete reduction of aldehydes to alkanes.
• Specialized procedures (e.g. Clemmensen or Wolff–Kishner reductions) to remove the carbonyl group of ketones, giving alkanes.

These methods are primarily synthetic tools for “deoxygenation” of carbonyl compounds.

Oxidation of Aldehydes

A key difference between aldehydes and ketones:

• Aldehydes are readily oxidized to carboxylic acids.
• Simple ketones are more resistant to mild oxidation; they typically require more drastic conditions to undergo oxidative cleavage of the carbon–carbon bonds adjacent to the carbonyl.

General oxidation of an aldehyde:

$$
R{-}CHO + [O] \rightarrow R{-}COOH
$$

Here $[O]$ represents a suitable oxidizing agent (such as permanganate, dichromate, or milder reagents depending on context). This reaction is highly useful both synthetically and in analysis (e.g. qualitative tests for aldehydes).

Ketones, under mild conditions, usually do not undergo analogous oxidation to an acid with the same carbon skeleton.

Carbonyl Compounds as Oxidizing Agents

Because aldehydes are oxidized to carboxylic acids, they can act as mild reducing agents, reducing other species (e.g. certain metal ions) while themselves being oxidized. Some classical analytical tests for aldehydes are based on this ability (e.g. silver mirror formation), but the analytical details are discussed elsewhere.

Tautomerism Involving Carbonyl Compounds (Enol Forms)

Many aldehydes and ketones can exist in equilibrium with their corresponding enol forms (a double bond with an $OH$ group attached, $C{=}C{-}OH$):

$$
\text{Carbonyl form} \rightleftharpoons \text{Enol form}
$$

Example:

$$
CH_3{-}CO{-}CH_3 \rightleftharpoons CH_3{-}C(OH){=}CH_2
$$

Key points (qualitative here):

• The carbonyl form usually predominates at equilibrium for simple aldehydes and ketones.
• The conversion involves migration of a hydrogen and shift of a double bond (keto–enol tautomerism).
• Even small amounts of the enol form can be important for reactions occurring at the $\alpha$-position (e.g. halogenation, aldol reactions, etc.), which are covered elsewhere.

Overview of Synthetic Importance and Natural Occurrence

Synthetic Building Blocks

Aldehydes and ketones play central roles in organic synthesis:

• They are easily prepared from corresponding alcohols (oxidation) or by various carbon–carbon bond-forming reactions.
• They undergo many types of transformations that introduce new carbon–carbon bonds, especially via nucleophilic addition to the carbonyl or reactions of their enolate forms.
• They can be temporarily transformed into acetals/ketals, imines, or enamines, which serve as “protected” or “activated” versions of the carbonyl.

Occurrence in Nature and Applications

Many biologically important molecules contain aldehyde or ketone functions:

• Sugars (in their open-chain forms) often contain aldehyde (aldoses) or ketone (ketoses) groups.
• Some vitamins, hormones, and signaling molecules feature carbonyl groups.
• Carbonyl compounds are key components in flavors, fragrances, and solvents (e.g. acetone as a widely used solvent).

Their combination of polarity, reactivity, and relative stability makes carbonyl compounds one of the most important functional group families in organic chemistry.

Summary of Key Points for Carbonyl Compounds

• The carbonyl group $C{=}O$ is planar, strongly polarized, and central to the chemistry of aldehydes and ketones.
• Aldehydes ($R{-}CHO$) and ketones ($R{-}CO{-}R'$) differ in substitution at the carbonyl carbon, affecting both physical properties and reactivity.
• Nucleophilic addition to the electrophilic carbonyl carbon is the defining reaction type of aldehydes and ketones.
• Typical nucleophilic additions: water (hydrates), alcohols (hemiacetals/acetals), $HCN$ (cyanohydrins), and amines (imines/enamines).
• Aldehydes are more reactive than ketones and are readily oxidized to carboxylic acids; ketones resist mild oxidation.
• Carbonyl compounds can be reduced to alcohols and, under stronger conditions, to hydrocarbons.
• Keto–enol tautomerism connects carbonyl compounds to their enol forms, which are crucial in reactions at the $\alpha$-position.