Deprotonation (acetylide formation)

Deprotonation (acetylide formation) Definition:


Deprotonation is a treatment of acetylene with a strong base such as NaNHor NaH where acetylide (alkynide) anion is obtained.



Deprotonation (acetylide formation) Explained:


Acetylide (Alkynide) anions are strong nucleophiles, capable of reacting with electrophiles such as alkyl halides and epoxides.


Reaction of Acetylide Anions with Alkyl Halides

Alkylation is the transfer of an alkyl group from one molecule to another. This transformation proceeds via an SN2 reaction and it is achieved in just two steps. The first step is deprotonation of the alkyne by a strong base (reaction above), and the second step is the nucleophilic attack of the acetylide anion to the alkyl halide.



This is a case when we have internal alkyne, but if we have terminal alkyne (i.e. acetylene) which possesses two terminal protons (one on either side) and can, therefore, undergo alkylation twice. One side of acetylene is first alkylated, and then, in a separate process, the other side is alkylated. This can work complicated, but this requirement provides an additional synthetic utility. It enables the installation of two different alkyl groups.



Although nucleophilic substitution with acetylide anions is a very valuable carbon-carbon bond-forming reaction, it has the same limitations as any SN2 reaction. This process is only efficient with methyl or primary alkyl halides. Steric hindrance around the leaving group causes secondary and tertiary alkyl halides to undergo elimination by an E2 mechanism.


Reaction of Acetylide Anions with Epoxides

Acetylide anions are strong nucleophiles that can open epoxide rings by an SN2 mechanism. The reaction also results in the formation of a new carbon-carbon bond. Backside attack occurs at the less substituted end of the epoxide.