Nucleophilic addition

The nucleophilic addition (A _{N for} short ) ( see: nucleophilicity ) is a reaction mechanism in organic chemistry in which a nucleophile ( anion or Lewis base ) attacks a multiple bond. The nucleophile is added to the attacked compound ( addition ). There is no exchange of atoms or groups of atoms ( compare with: substitution ).

Educts

Nucleophile

A wide variety of compounds can be used as nucleophiles. These are electron-rich , mostly containing free electron pairs , molecules or anions ( see below: Examples).

Multiple bonds

Nucleophilic additions can take place on different types of multiple bonds:

Addition to C = C double bonds
Addition to C≡C triple bonds
Addition to conjugated CC multiple bonds
Addition to CX multiple bonds

Reaction course

The addition of the nucleophile is normally controlled thermodynamically; the nucleophile is attached to the multiple bond in such a way that an anion that is as stable as possible results (compare the justification of the Markovnikov rule ). In the case of C- X multiple bonds, the stabilization takes place through the heteroatoms themselves, in the case of substituted CC multiple bonds through the inductive influences of substituents , but especially through substituents with an -M effect . Since such substituents simultaneously positively affect the more distant carbon atom of the double bond, the addition at this is also kinetically favored.

Nucleophilic addition to CC multiple bonds

The first step in this reaction is the attack of the nucleophile to form a carbanion :

X stands for the nucleophile, Z for the electron-withdrawing substituent.

In the second step, the carbanion reacts with an electron acceptor , usually a proton :

Y is the electron acceptor.

The formation of the carbanion is strongly favored if the substituents can stabilize it through mesomerism . One then speaks of a Michael addition , the nucleophile being the anion of a CH-acidic compound.

Nucleophilic addition to CX multiple bonds

CX multiple bonds occur in the following atomic groups:

Here a nucleophile can attack the carbon of a CX multiple bond. The other possibility is that first the electron-withdrawing heteroatom is protonated in an upstream equilibrium and then the nucleophile binds to the carbon.

Examples

Nucleophilic addition to CC multiple bonds

Addition of ammonia or amines
Addition of hydrogen cyanide
Michael addition

Nucleophilic addition to CX multiple bonds

The individual nucleophilic additions to CX multiple bonds can be divided into groups based on the attacking nucleophile:

Nitrogen as a nucleophile

Addition of primary amines: This reaction leads to a compound corresponding to a hemiacetal (hemiaminal), which is converted into an azomethine in a subsequent reaction with elimination of water .

Addition of a primary amine as a nucleophile to a carbonyl group. The alkyl radical of the amine is denoted by R.

Addition of secondary amines: This reaction ultimately leads to an enamine .
Addition of hydrazine
Addition of hydroxylamine
Mannich reaction

Sulfur as a nucleophile

Mercaptal formation
Bisulfite addition

Carbanionic carbon as a nucleophile

Individual evidence

^ Benno Krieg, Christoph Janiak: Chemistry for medical professionals . ISBN 978-3-11-017999-6 ( page 259 (nucleophilic additions in aldehydes and ketones) in the Google book search).
↑ Singh: Advanced Organic Chemistry: Reactions And Mechanisms . Pearson, 2004, ISBN 978-81-317-1107-1 ( page 193 (nucleophilic addition to alkenes and alkynes) in the Google book search).
^ Marye Anne Fox, James K. Whitesell: Organic chemistry . ISBN 978-0-7637-2197-8 ( page 571ff (nucleophile, addition or substitution at carbonyl groups) in the Google book search).
↑ Alan R. Katritzky, Stanley M. Roberts, Otto Meth-Cohn, Charles Wayne Rees: Comprehensive organic functional group transformations . ISBN 978-0-08-042322-7 ( page 286 in the google book search).
^ ^A ^b Alan R. Katritzky: Advances in heterocyclic chemistry, Volume 95 . 2008, ISBN 978-0-12-374272-8 ( page 70 in the Google book search).

[buch-1] Benno Krieg, Christoph Janiak: Chemistry for medical professionals . ISBN 978-3-11-017999-6 ( page 259 (nucleophilic additions in aldehydes and ketones) in the Google book search).

[Singh-2] Singh: Advanced Organic Chemistry: Reactions And Mechanisms . Pearson, 2004, ISBN 978-81-317-1107-1 ( page 193 (nucleophilic addition to alkenes and alkynes) in the Google book search).

[buch2-3] Marye Anne Fox, James K. Whitesell: Organic chemistry . ISBN 978-0-7637-2197-8 ( page 571ff (nucleophile, addition or substitution at carbonyl groups) in the Google book search).

[Comprehensive-4] Alan R. Katritzky, Stanley M. Roberts, Otto Meth-Cohn, Charles Wayne Rees: Comprehensive organic functional group transformations . ISBN 978-0-08-042322-7 ( page 286 in the google book search).

[Katritzky-5] A ^b Alan R. Katritzky: Advances in heterocyclic chemistry, Volume 95 . 2008, ISBN 978-0-12-374272-8 ( page 70 in the Google book search).