The Glaser–Hay reaction: optimization and scope based on 13C NMR kinetics experiments

Mie Højer Vilhelmsen; Jonas Jensen; Christian Tortzen; Mogens Brøndsted Nielsen

doi:10.1002/ejoc.201201159

The Glaser–Hay reaction: optimization and scope based on ¹³C NMR kinetics experiments

Mie Højer Vilhelmsen, Jonas Jensen, Christian Tortzen, Mogens Brøndsted Nielsen

Kemisk Institut

64 Citationer (Scopus)

Abstract

The oxidative Glaser–Hay coupling of two terminal alkynes to furnish a butadiyne is a key reaction for acetylenic scaffolding. Although the reaction is performed under rather simple conditions [CuCl/TMEDA/O2 (air)], the mechanism is still under debate. Herein we present detailed studies on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl-substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found to be zero-order with respect to the terminal alkyne reactant under standard preparative conditions. Moreover, as the reaction proceeded, a clear change to slower reaction kinetics was observed, but it was still apparently zero-order. The onset of this change was found to depend on the catalyst loading. This unfavorable change in reaction profile could be avoided by adding molecular sieves to the reaction mixture, thereby removing the water that is accumulated from the air and produced in the reaction in which dioxygen acts as the oxidizing agent. Not unexpectedly, the stirring rate, and hence uptake of air (O2), was found to have a significant effect on the rate of the reaction: The percentage of alkyne remaining after a certain time decreased linearly with the rate of stirring. On the basis of systematic studies, the optimized conditions for the coupling reaction using CuCl/TMEDA as the catalyst system are presented. Finally, we investigated the effect of different ligands and found that piperidine can also be conveniently employed as a ligand, albeit monodentate, in accord with related studies.

Originalsprog	Engelsk
Tidsskrift	European Journal of Organic Chemistry
Vol/bind	2013
Udgave nummer	4
Sider (fra-til)	701-711
Antal sider	11
ISSN	1434-193X
DOI	https://doi.org/10.1002/ejoc.201201159
Status	Udgivet - feb. 2013

Emneord

Alkynes
Copper
N ligands
NMR spectroscopy
Oxidation
C–C coupling

Adgang til dokumentet

10.1002/ejoc.201201159

Citationsformater

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title = "The Glaser–Hay reaction: optimization and scope based on 13C NMR kinetics experiments",

abstract = "The oxidative Glaser-Hay coupling of two terminal alkynes to furnish a butadiyne is a key reaction for acetylenic scaffolding. Although the reaction is performed under rather simple conditions [CuCl/TMEDA/O2 (air)], the mechanism is still under debate. Herein we present detailed studies on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl-substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found to be zero-order with respect to the terminal alkyne reactant under standard preparative conditions. Moreover, as the reaction proceeded, a clear change to slower reaction kinetics was observed, but it was still apparently zero-order. The onset of this change was found to depend on the catalyst loading. This unfavorable change in reaction profile could be avoided by adding molecular sieves to the reaction mixture, thereby removing the water that is accumulated from the air and produced in the reaction in which dioxygen acts as the oxidizing agent. Not unexpectedly, the stirring rate, and hence uptake of air (O2), was found to have a significant effect on the rate of the reaction: The percentage of alkyne remaining after a certain time decreased linearly with the rate of stirring. On the basis of systematic studies, the optimized conditions for the coupling reaction using CuCl/TMEDA as the catalyst system are presented. Finally, we investigated the effect of different ligands and found that piperidine can also be conveniently employed as a ligand, albeit monodentate, in accord with related studies. Based on 13C NMR and UV/Vis kinetics studies, the rate of the oxidative Glaser-Hay homocoupling reaction of terminal alkynes was found to be apparently zero-order in the terminal alkyne. As the reaction proceeds, a change to slower zero-order kinetics is observed, which can be avoided in the presence of molecular sieves (MS). The stirring rate has the most significant impact on the reaction rate.",

keywords = "Alkynes, Copper, N ligands, NMR spectroscopy, Oxidation, C–C coupling",

author = "Vilhelmsen, {Mie H{\o}jer} and Jonas Jensen and Christian Tortzen and Nielsen, {Mogens Br{\o}ndsted}",

year = "2013",

month = feb,

doi = "10.1002/ejoc.201201159",

language = "English",

volume = "2013",

pages = "701--711",

journal = "European Journal of Organic Chemistry",

issn = "1434-193X",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "4",

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TY - JOUR

T1 - The Glaser–Hay reaction

T2 - optimization and scope based on 13C NMR kinetics experiments

AU - Vilhelmsen, Mie Højer

AU - Jensen, Jonas

AU - Tortzen, Christian

AU - Nielsen, Mogens Brøndsted

PY - 2013/2

Y1 - 2013/2

N2 - The oxidative Glaser-Hay coupling of two terminal alkynes to furnish a butadiyne is a key reaction for acetylenic scaffolding. Although the reaction is performed under rather simple conditions [CuCl/TMEDA/O2 (air)], the mechanism is still under debate. Herein we present detailed studies on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl-substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found to be zero-order with respect to the terminal alkyne reactant under standard preparative conditions. Moreover, as the reaction proceeded, a clear change to slower reaction kinetics was observed, but it was still apparently zero-order. The onset of this change was found to depend on the catalyst loading. This unfavorable change in reaction profile could be avoided by adding molecular sieves to the reaction mixture, thereby removing the water that is accumulated from the air and produced in the reaction in which dioxygen acts as the oxidizing agent. Not unexpectedly, the stirring rate, and hence uptake of air (O2), was found to have a significant effect on the rate of the reaction: The percentage of alkyne remaining after a certain time decreased linearly with the rate of stirring. On the basis of systematic studies, the optimized conditions for the coupling reaction using CuCl/TMEDA as the catalyst system are presented. Finally, we investigated the effect of different ligands and found that piperidine can also be conveniently employed as a ligand, albeit monodentate, in accord with related studies. Based on 13C NMR and UV/Vis kinetics studies, the rate of the oxidative Glaser-Hay homocoupling reaction of terminal alkynes was found to be apparently zero-order in the terminal alkyne. As the reaction proceeds, a change to slower zero-order kinetics is observed, which can be avoided in the presence of molecular sieves (MS). The stirring rate has the most significant impact on the reaction rate.

AB - The oxidative Glaser-Hay coupling of two terminal alkynes to furnish a butadiyne is a key reaction for acetylenic scaffolding. Although the reaction is performed under rather simple conditions [CuCl/TMEDA/O2 (air)], the mechanism is still under debate. Herein we present detailed studies on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl-substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found to be zero-order with respect to the terminal alkyne reactant under standard preparative conditions. Moreover, as the reaction proceeded, a clear change to slower reaction kinetics was observed, but it was still apparently zero-order. The onset of this change was found to depend on the catalyst loading. This unfavorable change in reaction profile could be avoided by adding molecular sieves to the reaction mixture, thereby removing the water that is accumulated from the air and produced in the reaction in which dioxygen acts as the oxidizing agent. Not unexpectedly, the stirring rate, and hence uptake of air (O2), was found to have a significant effect on the rate of the reaction: The percentage of alkyne remaining after a certain time decreased linearly with the rate of stirring. On the basis of systematic studies, the optimized conditions for the coupling reaction using CuCl/TMEDA as the catalyst system are presented. Finally, we investigated the effect of different ligands and found that piperidine can also be conveniently employed as a ligand, albeit monodentate, in accord with related studies. Based on 13C NMR and UV/Vis kinetics studies, the rate of the oxidative Glaser-Hay homocoupling reaction of terminal alkynes was found to be apparently zero-order in the terminal alkyne. As the reaction proceeds, a change to slower zero-order kinetics is observed, which can be avoided in the presence of molecular sieves (MS). The stirring rate has the most significant impact on the reaction rate.

KW - Alkynes

KW - Copper

KW - N ligands

KW - NMR spectroscopy

KW - Oxidation

KW - C–C coupling

U2 - 10.1002/ejoc.201201159

DO - 10.1002/ejoc.201201159

M3 - Journal article

SN - 1434-193X

VL - 2013

SP - 701

EP - 711

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

IS - 4

ER -