Glaser coupling is an oxidative homocoupling reaction in which two molecules of the same type of terminal alkyne are joined to form a 1,3-diyne. Because two units derived from the same alkyne are coupled, the product is generally a symmetrical diyne. ^[1–2]

The reaction is named after German chemist Carl Andreas Glaser, who reported in 1869 that copper(I) phenylacetylide underwent oxidative coupling on exposure to air.

General Reaction

The general reaction can be represented as: ^[1–2]

2 R–C≡C–H → R–C≡C–C≡C–R

During the reaction, a new carbon–carbon single bond forms between the terminal carbon atoms of the two alkyne molecules. The two C≡C bonds are retained, producing a 1,3-diyne.

The reaction is typically carried out using copper and a base under oxidizing conditions.

Example

A common example is the coupling of phenylacetylene. Two molecules of phenylacetylene form 1,4-diphenylbuta-1,3-diyne. ^[1–2]

2 C₆H₅–C≡C–H → C₆H₅–C≡C–C≡C–C₆H₅

Simplified Mechanism

The detailed mechanism of Glaser coupling can vary depending on the copper system and reaction conditions. For learning purposes, the reaction can be understood using the following simplified sequence. ^[3–5]

Step 1: Formation of a Copper Acetylide-Type Species

The terminal alkyne interacts with copper in the presence of a base. The base assists in removing the terminal hydrogen, thereby forming a copper acetylide-type species. For simplicity, this copper-containing intermediate can be represented as:

R–C≡C–H → R–C≡C–Cu

Step 2: Oxidation and Association of the Alkynyl Groups

Copper-containing alkynyl species then participate in an oxidative process. During this oxidative stage, two copper-associated alkynyl groups are brought together in a suitable arrangement for C–C bond formation.

In many catalytic variants of the Glaser reaction, particularly the Glaser–Hay coupling, molecular oxygen (O₂) serves as the oxidant.

Step 3: Formation of the New C–C Bond

The copper-associated alkynyl groups couple, forming the 1,3-diyne:

R–C≡C–C≡C–R

The new central C–C single bond connects the two original alkyne units.

Step 4: Regeneration of the Copper Species

In catalytic versions of the reaction, the copper species is regenerated, allowing it to participate in another reaction cycle.