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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

We present protocols for the isolation of stable heterocyclic carbenes. The synthesis of a cyclic (alkyl)(amino) carbene (CAAC) and an N-heterocyclic carbene (NHC) is demonstrated using filter cannulas and Schlenk technique. We furthermore present the synthesis of the related oxygen-sensitive, electron-rich mixed “Wanzlick dimer” and the reduced stable organic radical.

Abstract

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the synthesis of their mixed CAAC–NHC “Wanzlick” dimer and the synthesis of the related stable organic “olefin” radical are presented. The main goal of this manuscript is to give a detailed and general protocol for the synthetic chemist of any skill level on how to prepare free heterocyclic carbenes by deprotonation using filter cannulas. Due to the air-sensitivity of the synthesized compounds, all experiments are performed under inert atmosphere using either Schlenk technique or a dinitrogen filled glovebox. Controlling Wanzlick’s equilibrium (i.e., the dimerization of free carbenes), is a crucial requirement for the application of free carbenes in coordination chemistry or organic synthesis. Thus, we elaborate on the specific electronic and steric requirements favoring the formation of dimers, heterodimers, or monomers. We will show how proton catalysis allows for the formation of dimers, and how the electronic structure of carbenes and their dimers affects the reactivity with either moisture or air. The structural identity of the reported compounds is discussed based on their NMR spectra.

Introduction

More than half a century ago, Wanzlick reported arguably the first attempts to synthesize N-heterocyclic carbenes1,2,3. However, instead of isolating the free carbenes, he succeeded only in characterizing their dimers. This observation prompted him to suggest an equilibrium between the olefin dimer and the respective free carbenes, which is now commonly referred to as “Wanzlick’s equilibrium” (Figure 1, I.)4,5,6. Later on, it w....

Protocol

CAUTION: Carry out all syntheses in a well-ventilated fume hood. Wear appropriate personal protective equipment (PPE) including a lab coat and safety goggles.

NOTE: The starting materials were synthesized according to the literature: 1-(2,6-diisopropylphenyl)-2,2,4,4-tetramethyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (1prot) (For the synthesis of CAACs, see:18,30,.......

Representative Results

Free carbenes react typically readily with water66. Hence, carefully dried glassware and solvents are required67. In the procedure described above, we used cannulas fitted with a glass micro fiber filter in order to separate air sensitive solutions from a precipitate under inert conditions. We used this technique for both the extraction of solids (i.e., the desired product is dissolved) as well as the washing of solid compounds (i.e., the de.......

Discussion

Herein, we present a general and adaptable protocol for the synthesis of stable carbenes (NHC, CAAC) and their electron rich dimer. All steps can readily be upscaled to at least a 25 g scale. Crucial for a successful synthesis are the strict exclusions of moisture (air, respectively) for the synthesis of the carbenes, and of oxygen (air, respectively) for the electron rich olefin. The herein applied filtration cannula technique in combination with a Schlenk line is a very convenient method to separate solutions from.......

Acknowledgements

The authors thank the Fonds der Chemischen Industrie for a Liebig fellowship and the Hertha and Helmut Schmauser foundation for financial support. Support by K. Meyer is gratefully acknowledged.

....

Materials

NameCompanyCatalog NumberComments
Equipment
Glass micro fiber filter, 691, 24 mm. Particle retention 1.6 mmVWR516-0859
magnetic stir barFengTecExvarious
PTFE tapeSigma-AldrichZ148814-1PAKPTFE tape used in this manuscript was obtained from a local supplier. Tape from Sigma Aldrich should show comparable performance.
rubber septumFengTecExRS112440Joint size: 24/29
rubber septumFengTecExRS111420Joint size: 14/23
rubber septumFengTecExRS111922Joint size: 19/26
schlenk flasksFengTecExvarious100 mL
steel cannulaFengtecExC702024Attachment of a steel joint by a machine shop not required, but facilitates preparation of filter cannula
syringe cannulaFengtecExS380221
NameCompanyCatalog NumberComments
Reactants
1-(2,6-diisopropylphenyl)-2,2,4,4-tetramethyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborateSynthesized according to: Jazzar, R., Dewhurst, R. D., Bourg, J. B., Donnadieu, B., Canac, Y., Bertrand, G. Intramolecular “Hydroiminiumation” of alkenes: Application to the synthesis of conjugate acids of cyclic alkyl amino carbenes (CAACs). Angewandte Chemie International Edition 46 (16), 2899-2902, (2007).
1,3-dimethyl-4,5-dihydro-1H-imidazol-3-ium iodideSynthesized according to: Benac, B. L., Burgess, E. M., Arduengo, A. J. 1,3-Dimethylimidazole-2-Thione. Organic Synthesis 64, 92, (1986).
potassium hexamethyldisilazideSigma-Aldrich324671-100GCAS 40949-94-8
silver trifluoromethanesulfonateSigma-Aldrich85325-25GCAS 2923-28-6
NameCompanyCatalog NumberComments
Solvents
acetonitrile-D3Deutero00202-10mdistilled from CaH2, stored over activated molecular sieves
benzene-D6Deutero00303-100mldried over activated molecular sieves, stored over potassium
diethylether--dried by two-column, solid-state purification system and degassed by three freeze-pump-thaw cycles, stored over activated molecular sieves
hexanes--dried by two-column, solid-state purification system and degassed by three freeze-pump-thaw cycles, stored over activated molecular sieves
tetrahydrofuran--dried by two-column, solid-state purification system and degassed by three freeze-pump-thaw cycles, stored over activated molecular sieves
toluene--dried by two-column, solid-state purification system and degassed by three freeze-pump-thaw cycles, stored over activated molecular sieves

References

  1. Wanzlick, H. W., Schikora, E. Ein neuer Zugang zur Carben-Chemie. Angewandte Chemie. 72, 494 (1960).
  2. Wanzlick, H. W., Kleiner, H. J. Nucleophile Carben-Chemie. Angewandte Chemie International Edition. 73 (14), 493 (1961).
  3. Wanzlick, H. W.....

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