Elsevier

Tetrahedron

Volume 58, Issue 33, 12 August 2002, Pages 6741-6747
Tetrahedron

The Glaser reaction mechanism. A DFT study

https://doi.org/10.1016/S0040-4020(02)00669-5Get rights and content

Abstract

A detailed mechanism for the Hey modification of the Glaser oxidative coupling of terminal acetylenes has been formulated based on DFT calculations. The mechanism includes Cu(I)/Cu(III)/Cu(II)/Cu(I) catalytic cycle and explains the dioxygen molecule activation mechanism by Cu(I) species to give water molecule as final product of dioxygen reduction. The key step of the reaction mechanism is the oxidation of Cu acetylide by molecular oxygen to form dicopper-dioxo complex with [Cu2(μ-O2)]2+ core. Relatively low activation energies found for the reaction steps support the viability of the formulated mechanism.

Introduction

The Glaser reaction was discovered more than 100 years ago by Glaser1 when copper phenylacetylide was oxydized to diphenyl diacetylene by air in ethanol solution of ammonia (Fig. 1). Since then the Glaser reaction and its modifications have widely been used to synthesize various symmetrical and unsymmetrical diacetylenes, diacetylene-containing polymers, and macrocycles. A comprehensive review of the Glaser reaction scope, techniques and limitations can be found in Ref. 2. The Glaser oxidative coupling reaction is one of the few C–C bond forming reaction which takes place under very mild conditions in aqueous solutions and in the presence of oxygen, thus resembling enzymatic reactions. Many modifications and improvements have been introduced since the Glaser reaction was discovered in 1869. Hydrogen peroxide, potassium permanganate, potassium ferrocianyde, iodine or Cu(II) can be used instead of oxygen as oxidants.2 The use of organic solvents (pyridine and cyclohexylamine) in the presence of catalytic amount of CuCl3., 4. allows one to avoid the isolation of copper acetylide during the reaction. On the other hand making use of N,N,N′,N′-tetramethylethylenediamine–CuCl complex the Glaser reaction can be carried out in almost any organic solvent with high yield.5., 6.

In spite of the fact that the Glaser type reactions have widely been used in preparative chemistry, the mechanism of this reaction is not completely understood. The most recent mechanism postulated for the Glaser condensation is one considering Cu(II) acting as oxidant.7 Although this mechanism takes into account such experimental observations as the second order reaction for alkynes and discards the radical mechanism, it is unable to describe the Glaser reaction involving molecular oxygen as oxidizing agent. Where the interplay between Cu complexes with different oxidation levels is of importance. When using molecular oxygen as oxidant for the Glaser condensation, Cu–O2 intermediated should play an important role which is not reflected in the proposed mechanism. It has been recently shown that molecular oxygen forms adducts with Cu(I) supported by tertiary amines8 which might be the intermediates in the Glaser reaction of this type (Scheme 1). From this point of view the Glaser condensation is one more example of binding and activation of dioxygen by copper ions which is important in numerous and diverse biological and catalytic processes.9 The establishing of detailed mechanism of the Glaser condensation in the presence of molecular oxygen could be an important step toward the understanding of action of copper enzymes.

This paper describes a computational study of the Glaser oxidative coupling reaction trying to take into account the most important experimental observations.

  • 1.

    The presence of amine is indispensable for the reaction to occur2

  • 2.

    Copper acetylides produce diacetylenes when oxidized by molecular oxygen2

  • 3.

    The reaction often takes place at room temperature that implies low activation energies for each step of condensation.

The oxidative coupling of acetylene in acetone media in the presence of catalytical amounts of N,N,NN′-tetraethylenediamine (TMEDA)–Cu(I) complex and molecular oxygen as oxidant was chosen as model reaction. This modification of Glaser condensation is known as the Hay reaction.5., 6.

Section snippets

Computational details

All calculation were carried out with Jaguar v 4.1 program.10 The geometry optimizations were run at B3LYP/LACVP level of theory.11., 12., 13., 14. LACVP basis set uses standard 6-31G basis set for the fist and second row elements and LAC pseudopotential for core electrons of third row and heavier elements.15 Restricted formalism was used to treat closed shell systems while for the open shell molecules unrestricted method was applied. The energy evaluation of each intermediate was carried out

Results and discussion

It is known that in the presence of ammonia CuCl forms [Cu(NH3)2]+ ions in aqueous media.18 Similar situation holds for TMEDA which is much more powerful complexation agent compared to ammonia forming Cu(TMEDA)+ ions in organic solvents. According to the latest mechanism proposed for the Glaser condensation the first step of this reaction is complexation of acetylene (A) with complex I ion leading to the formation of complex II (Scheme 2). As can be seen from the Table 2 this process is

Conclusions

A detailed mechanism for the Hay modification of the Glaser reaction has been formulated based on DFT study. The mechanism involves Cu(I)/Cu(III)/Cu(II)/Cu(I) catalytical cycle for this transformation. The key step for this reaction is the dioxygen activation occurring on the complexation of two molecules of acetylide V with molecular oxygen giving Cu(III) complex VI. The viability of this mechanism is supported by the fact of isolation and characterization of Cu(III) complexes similar to VI

Acknowledgements

This work was supported by a grant from CONACyT under contract 32560E.

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