A wide variety of carbon nucleophiles add to aldehydes, and such reactions are of prime importance in synthetic organic chemistry because the product is a combination of two carbon skeletons. Organic chemists have been able to assemble almost any carbon skeleton, no matter how complicated, by ingenious uses of these reactions. One of the oldest and most important is the addition of Grignard reagents (RMgX, where X is a halogen atom). French chemist Victor Grignard won the 1912 Nobel Prize in chemistry for the discovery of these reagents and their reactions.

Addition of a Grignard reagent to an aldehyde followed by acidification in aqueous acid gives an alcohol. Addition to formaldehyde gives a primary alcohol. Addition to an aldehyde other than formaldehyde gives a secondary alcohol.

Another carbon nucleophile is the cyanide ion, CN⁻, which reacts with aldehydes to give, after acidification, cyanohydrins, compounds containing an OH and CN group on the same carbon atom.

Benzaldehyde cyanohydrin (mandelonitrile) provides an interesting example of a chemical defense mechanism in the biological world. This substance is synthesized by millipedes (Apheloria corrugata) and stored in special glands. When a millipede is threatened, the cyanohydrin is secreted from its storage gland and undergoes enzyme-catalyzed dissociation to produce hydrogen cyanide (HCN). The millipede then releases the HCN gas into its surrounding environment to ward off predators. The quantity of HCN emitted by a single millipede is sufficient to kill a small mouse. Mandelonitrile is also found in bitter almonds and peach pits. Its function there is unknown.

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Other important reactions in this category include the Knoevenagel reaction, in which the carbon nucleophile is an ester with at least one α-hydrogen. In the presence of a strong base, the ester loses an α-hydrogen to give a negatively charged carbon that then adds to the carbonyl carbon of an aldehyde. Acidification followed by loss of a water molecule gives an α, β-unsaturated ester.

Another addition reaction involving a carbon nucleophile is the Wittig reaction, in which an aldehyde reacts with a phosphorane (also called a phosphorus ylide), to give a compound containing a carbon-carbon double bond. The result of a Wittig reaction is the replacement of the carbonyl oxygen of an aldehyde by the carbon group bonded to phosphorus. The German chemist Georg Wittig shared the 1979 Nobel Prize in chemistry for the discovery of this reaction and the development of its use in synthetic organic chemistry.

Compounds containing a trimethylsilyl group (―SiMe₃, where Me is the methyl group, ―CH₃) and a lithium (Li) atom on the same carbon atom react with aldehydes in the so-called Peterson reaction to give the same products that would be obtained by a corresponding Wittig reaction.

α-Halogenation

An α-hydrogen of an aldehyde can be replaced by a chlorine (Cl), bromine (Br), or iodine (I) atom when the compound is treated with Cl₂, Br₂, or I₂, respectively, either without a catalyst or in the presence of an acidic catalyst.

The reaction can easily be stopped after only one halogen atom is added. α-Halogenation actually takes place on the enol form (see above Properties of aldehydes: Tautomerism) of the aldehyde rather than on the aldehyde itself. The same reaction occurs if a base is added, but then it cannot be halted until all α-halogens attached to the same carbon have been replaced by halogen atoms. If there are three α-hydrogens on the same carbon, the reaction goes one step further, resulting in the cleavage of an X₃C⁻ ion (where X is a halogen) and the formation of the salt of a carboxylic acid.

This reaction is called the haloform reaction, because X₃C⁻ ions react with water or another acid present in the system to produce compounds of the form X₃CH, which are called haloforms (e.g., CHCl₃ is called chloroform).

Aldol reaction

Another important reaction of a carbon nucleophile with an aldehyde is the aldol reaction (also called aldol condensation), which takes place when any aldehyde possessing at least one α-hydrogen is treated with sodium hydroxide or sometimes with another base. The product of an aldol reaction is a β-hydroxyaldehyde.