Introduction

Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.

The reaction takes place in two steps:

1. The first step is the deprotonation of the terminal alkyne by the strong base forming an acetylide ion.

2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C–C bond.

Reaction Mechanism —S_N2 pathway

Acetylide ions are strong bases and can also function as good nucleophiles. The substitution reaction follows an S_N2 pathway where the nucleophilic acetylide ion attacks the electrophilic carbon of the primary alkyl halide from the backside.

Since this is a concerted process, the nucleophilic attack and the departure of the leaving group takes place simultaneously to form the product with an inverted stereochemistry at the reaction center.

The reaction works best with unhindered alkyl halides like methyl halide and other primary halides. With secondary and tertiary alkyl halides, acetylide ions act as strong bases, in which case E2 elimination is the preferred pathway.

Application in organic synthesis

Alkylation of simple terminal alkynes is a useful method to extend the length of the carbon chain. Acetylene, a terminal alkyne, can be converted to a higher internal alkyne by repeated alkylation as shown below: