Based on Michael Bessel’s work on the synthesis of trimethylene-linked bisimidazoli- nium salts and their use as ligands in dinuclear copper(I) halide complexes,[112a] it was attempted to synthesize dinuclear copper complexes with bisimidazolinylidene li- gands. 1-(2,6-Dimethylphenyl)-4,5-dihydro-1H-imidazole was used as a readily avai- lable starting material.[112] In order to introduce a xylylene-linker, the imidazoline was reacted with 1,3-bis(chloromethyl)benzene. The double SN2 reaction proceeded
smoothly without solvent, as both substances have a low melting point: 1-(2,6-dime- thylphenyl)imidazoline melts at 64 °C and 1,3-bis(chloromethyl)benzene at 35 °C. In order to prevent the presence of strongly coordinating halide ions in the following steps, an in situ salt metathesis with hexafluorophosphoric acid was carried out to obtain 3,3'-[1,3-phenylenebis(methylene)]bis[1-(2,6-dimethylphenyl)-4,5-dihydro-1H- imidazol-3-ium] bis(hexafluorophosphate) (11). In our group, the yield of this reaction has been increased to 82 %.[119]
Scheme 41: Synthesis of 3,3'-[1,3-phenylenebis(methylene)]bis[1-(2,6-dimethylphenyl)-4,5- dihydro-1H-imidazol-3-ium] bis(hexafluorophosphate) (11).
With this material at hand, the synthesis of copper(I) complexes was attempted. In NMR or small-scale preparative experiments under inert gas conditions, the starting material 11 was mixed with a copper(I) precursor and a base in different solvents and stirred at room temperature (Table 9).
Table 9: Attempted syntheses of dicopper complexes from bisimidazolinium salt 11.
entry solvent base (eq.) copper(I) precursor (eq.) observation 1 d6-acetone DIPEA (excess) (IPr)CuOAc (2.0 eq.)
decomposition of the imidazoli- nium heterocycle, probably due to traces of water in the reaction mixture
2 d3-aceto-
nitrile
NEt3 (IPr)CuOAc
(2.5 eq.)
no reaction at room temperature
3 d3-aceto- nitrile NEt3 (IPr)CuOAc (2.5 eq.) no reaction at 70 °C within 18 hours 4 d3-aceto- nitrile NaH (> 3 eq.) (IPr)CuOAc (2.5 eq.)
decomposition of the starting ma- terial
5 THF NaH
(2.2 eq.)
CuOAc (2.3 eq.)
first greyish green suspension, then black precipitate; after filtra- tion and re-crystallization from THF/diethyl ether very small amount of white crystals; mass spectrum shows peak at
6 THF KH (2.8 eq.)
CuOAc (2.2 eq.)
black solid residue, green solu- tion: decomposition
7 d6-acetone K2CO3
(2.2 eq.)
CuOAc (5.3 eq.)
decomposition of the imidazoli- nium heterocycle, probably due to the presence of water
8 acetonitrile NaH (2.2 eq.)
CuOAc (2.5 eq.)
black solid residue, dark grey solution; 1H NMR of raw product in d6-acetone: deprotonation
almost complete, formation of a new species; acetone solution first turned green, then orange; no product isolated 9 d3-aceto- nitrile NaH (4.5 eq.) (H3CCN)4CuPF6 (2.5 eq.)
evolution of gas upon addition of NaH, black solid residue, colour- less solution; 1H NMR: deproto- nation complete, various new species 10 d3-aceto- nitrile DIPEA (4.5 eq.) (H3CCN)4CuPF6 (2.5 eq.)
solution turns pink upon addition of DIPEA; 1H NMR: deprotona- tion incomplete, various new spe- cies
11 acetonitrile DIPEA (excess)
CuOAc (2.5 eq.)
solution turns pink upon addition of DIPEA and exposure to ultra- sound; 1H NMR: deprotonation complete, new peak at 11.2 ppm with integral 2 (protonated
DIPEA); one product species (Figure 14) 12 d3-aceto- nitrile DIPEA (excess) CuBr (2.2 eq.), copper powder
no reaction, starting material unaltered 13 d3-aceto- nitrile DIPEA (excess) (CuBr • SMe2)2 (1.1 eq.)
8 hours at 60 °C: mostly starting material; additional 6 hours at 75 °C: starting material and new species; additional 5 days at
80 °C: starting material and pro- duct mixture 14 d3-aceto- nitrile NaH (8.8 eq.) (CuBr • SMe2)2 (1.1 eq.)
black precipitate, decomposition
15 d3-aceto- nitrile NEt3 (excess) (CuBr • SMe2)2 (1.1 eq.)
homogeneous solution, starting material and unidentified product 16 d3-aceto- nitrile NaHMDS (2.2 eq.) (CuBr • SMe2)2 (1.1 eq.)
deprotonation complete, low solubility, species in 1H NMR unidentified
Ligand precursor 11 was found to be very sensitive towards water under basic condi- tions as the presence of hydroxide ions in the basic reaction mixture leads to decom- position of the imidazolinium salt, probably by ring opening as depicted in Scheme 42.
This was confirmed by blind testing in the absence of copper species. The formation of the formamide decomposition product is indicated by a new peak at approximately 8.4 ppm in the 1H NMR spectrum. It was thus necessary to strictly exclude any traces of water.
Scheme 42: Hypothesis regarding the decomposition pathway of bisimidazolinium salt 11 in basic media in the presence of water.
There were only two experiments that looked promising, namely entries 5 and 11 in Table 9. In an attempt to synthesize a dinuclear copper(I) complex with acetate as sacrificial ligand, the ligand precursor bisimidazolinium salt 11 was suspended in THF together with sodium hydride and copper(I) acetate. After some minutes of stirring at room temperature under inert gas conditions, the reaction mixture turned green and a
grey precipitate was formed. After 20 hours of stirring, the grey solution with black so- lid residue was filtered over a filter paper-capped canula and the residue was washed with THF. Diethyl ether was added to the solution and the Schlenk flask stored at -20 °C. After a few days, a small amount of colourless crystals had precipitated. Unfortunately, they were not suitable for single crystal X-ray analysis. As the quantity was not sufficient for taking an NMR spectrum, the crystals were subjected to mass spectrometry. In the ESI+ spectrum, the largest peak was observed at m/z = 513.20726. This peak is in accordance with the molecular formula of the monocation [C30H34CuN4]+ (structures A and B in Figure 13) with m/z (calculated) = 513.20740. In
structural outline B, both NHC units coordinate to one copper ion, whereas a free car- bene is supposed to be generated on one side under the conditions of ESI+ mass spectrometry to give species A. On the other hand, a dication of formula [C60H68Cu2N8]2+ (structure C in Figure 13) would produce the observed m/z signal as
well. However, this species itself can be excluded by the isotopic pattern, which indicates the presence of only one copper ion. Nevertheless, formation of species C in the reaction mixture cannot be ruled out completely, as the latter might decompose under the conditions of ESI+ mass spectrometry to give A or B. Thus, the structure of the product complex cannot be derived from the ESI+ mass spectrum.
Figure 13: Detail from the ESI+ mass spectrum of the crystals obtained from the reaction mixture of entry 5 in Table 9 and plausible structures of copper complexes that fit to the signal at m/z = 513.20726.
In experiment 11, the deprotonation of the starting material by DIPEA was complete after ten minutes at room temperature with exposure to ultrasound. In the NMR spec- trum in CD3CN, one single product species was observed apart from the protonated
base (peaks at 11.22, 3.10, 2.56 and 1.03 ppm). However, it is indecisive whether acetate (peak at 2.04 ppm) coordinates to the copper centres, i.e. whether the de- sired bis-NHC-dicopper diacetate complex is existent. Alternatively, a dinuclear com- plex containing two bis-NHC ligands (structure C in Figure 13) with acetate as coun- terion might be formed. This question could have only been decided by crystal struc- ture analysis or elemental analysis.
Figure 14: 1H NMR spectra of the starting material bisimidazolinium salt 11 (upper part, red) and of the reaction mixture after ten minutes of ultrasound exposure at room temperature (lower part, blue) (spectra recorded in CD3CN at 250 MHz).
While these studies were underway, thiol-functionalized triazolium salts were investi- gated by Stefanie Seitz in the Straub group.[120] These ligand precursors can be syn- thesized from easily available starting materials and are more acidic than the corres- ponding imidazolinium salts. Despite the hints on the formation of copper complexes
in the experiments summarized in Table 9, the work with bisimidazolinium salts was abandoned in favour of studies on bistriazolylidene ligands.