It is known that carbene complexes of transition metals catalyze condensation reactions (Suzuki-Miyaura, Sonogashira, Stille, Kumada, Mizoroki-Heck reactions), olefin metathesis, reduction of multiple bonds, olefin polymerization, etc. [13]. Stable carbenes are also reactive in transesterification, the Claisen condensation, and the benzoin and formoin condensations [4]. Especially valuable in this respect are heterocyclic carbenes and their complexes which have the most stable carbene structures. Among these catalytic conversions, reduction by a hydrogen transfer from alcohols to the multiple bonds, which includes reduction of carbonyl compounds, imines and olefins [1], is interesting but rather poorly studied. It is known that these reactions are catalyzed by rhodium(I-III), iridium(I-III) and ruthenium(I-III) carbene complexes [524]. Complexes of the type of compounds 1-9 (Fig.1) which with similar effectiveness noticeably accelerate reduction of ketones by 2-propanol in alkaline media (hydrogen transfer) should be distinguished among them.

Figure 1
figure 1

Carbene complexes used as hydrogen transfer catalysts.

To assess the catalytic activity turnover numbers (TON) and turnover frequencies (TOF) are often used in literature. In case of the benzophenone reduction by ruthenium complex catalyst 1 TON is equal to 4700, while TOF is equal to 780 h–1 [16]. Similar process with iridium complex 8 is characterized by TON equal to 1800, and TOF equal to 1800 h–1 [18]. When using rhodium complex 9 for catalyzing the benzophenone reduction, the highest TON is obtained (10580), however TOF in this case is substantially lower (441 h–1) [7]. Reaction time in case of using this catalyst is still quite long (up to 24 h), and reduction product yields do not exceed 85–86 %. Significant disadvantage of all mentioned catalysts 19 is a high price of rhodium, ruthenium and iridium derivatives.

The objective of this work is to study the catalytic efficiency of carbenes and carbene complexes of such transition metals as nickel(II), palladium(II), and copper(I) in the reduction of ketones with 2-propanol in the presence of potassium hydroxide.

Mono- and biscarbene complexes of copper(I), carbene chelate and biscarbene complexes of nickel and palladium, and polymeric complexes of copper(I) were used as carbene complex catalysts.

According to our proposed method, monocarbene complex 11 (Scheme 1) was synthesized by reaction of the salt 10 with copper(I) chloride in acetonitrile in the presence of triethylamine.

Scheme 1
scheme 1

 

Biscarbene complexes 13, 14 (Scheme 2) were obtained by refluxing the solutions of 2 H-cyanomethylbenzimidazoline (12) with transition metal salts (copper(I) iodide or bis(triphenylphosphine)nickel(II) chloride) in acetonitrile. X-ray structural analysis results for complexes 11 and 13 are presented in [26].

Scheme 2
scheme 2

 

The potassium complex 16 was obtained by interaction of the hydroxyphenyl-substituted salt 15a with potassium tert-butoxide in toluene. According to the method described in paper [27], the chelate carbene complex 17a (Scheme 3) was formed in the reaction of the compound obtained with nickel perchlorate (dimethyl formamide complex, 1:4-1:5). The X-ray data for structure 17a are given in papers [27,28].

Scheme 3
scheme 3

 

By heating salt 15b with palladium acetate the palladium bistriazolylidene complex of 18 was formed, which was further dehydrobrominated in situ for chelation, following the method described in [29] (Schemes 2, 3), to give the chelate complex 17b.

The biscarbene complex 20 (Scheme 4) was synthesized by the reaction of the corresponding stable 1,2,4-triazol-5-ylidene 19 [30] with palladium chloride in acetonitrile.

Scheme 4
scheme 4

 

The polymeric complex 22 (Scheme 5) was obtained by the reaction of the crown-salt – 1,1',3,3'-bis(3-oxa- 1,5-pentylene)bisbenzimidazolium acetylacetonate (21) with copper(I) iodide.

Scheme 5
scheme 5

 

The specific signal of the benzyl CH2 protons (5.76 ppm) was observed in the 1 H NMR spectrum of complex 11 in CDCl3. In the 13C NMR spectrum the signal of methylene carbon atom appears at 51.2 ppm, while the signal of C-2 carbenoid carbon atom appears at 188.6 ppm. In the 1 H NMR spectrum of the complex 13 in DMSO-d6, a characteristic signal of methyl groups protons is observed (4.06 ppm), and in the 13C NMR spectrum, signals of methyl group carbon atoms (34.3 ppm) and C-2 carbenoid carbon atom (190.7 ppm) are observed. In the 1 H NMR spectrum of the nickel complex 14 in a mixture of DMSO-d6 and Py-d5, a characteristic signal of the methyl group protons is observed at 4.47, which is slightly shifted downfield relatively to the same signal for the complex 13, and in the 13C NMR spectrum, the methyl group carbon signals (35.7 ppm) and carbenoid carbon signal (180.6 ppm) are observed. For the chelate complex 17b in the 1 H NMR spectrum in CDCl3, a singlet signal of the tert-butyl methyl protons is observed (1.60 ppm), whereas specific signals in the 13C NMR spectrum are those of the (CH3)3 C group carbon atoms (30.8 and 62.6 ppm), C-3 triazole carbon atom (153.0 ppm), C–O bond carbon atom (161.7 ppm) and C-2 carbenoid carbon atom (171.1 ppm). In the 13C NMR spectrum of the corresponding palladium complex 20 in DMSO-d6, the carbenoid carbon atom signal is downfield shifted (171.0 ppm) relatively to the same signal of the nickel complex 14, but nearly coincide with the signal from chelate palladium complex 7b.

In the 1 H NMR spectrum of the macrocycle carbene complex 22 in DMSO-d6, the bridging fragment CH2O methylene groups signals (3.82 ppm) and CH2N groups signals (4.30–4.70 ppm) are observed. Due to the low solubility of this complex the 13C NMR spectrum measurement was performed in a solid state, and characteristic signals of the aliphatic fragments CH2O and CH2N carbon atoms were observed (48.3 and 69.4 ppm, respectively) as well as the C-2 carbenoid carbon atoms signals (154.8, 164.9 ppm). Molecular mass of the polymer 22 was determined by LC (see Experimental) as at average equal to 77 monomer units (Mw 43700; M n 42400 (Mw/M n  = 1.03)).

Catalytic efficiency of the obtained complexes in a ketone reduction reaction was studied to compare their catalytic properties. Reduction of 4-biphenyl phenyl ketone (23) and benzophenone 24 (Scheme 6) carbonyl groups was carried out in boiling 2-propanol in the presence of potassium hydroxide (50–100 mol%), using catalysts listed in the Table 1. Main experimental results for reduction of the ketones 23, 24 are presented in the Table 1.

Scheme 6
scheme 6

 

Table 1 Catalytic Efficiency of Synthesized Azolium Salts*

As it can be seen from the data in Table 1, using of potassium 2-propoxide was rather inefficient (Exp. No. 1), and noticeable better results were obtained with the use of potassium hydroxide (Exp. No. 2). Azolium alkoxide, generated from the salt 10, has insignificant catalytic effect on the ketone 23 reduction (Exp. No. 3–5). Yields of the carbinol 25 were increased in experiments with 2-propoxide and potassium hydroxide using 10 mol% of the catalyst. Maximum yield of the carbinol 25 using potassium 2-propoxide was obtained only in case of the salt 10 amount of 100 mol% and was equal to 56 % (Exp. No. 4). Thus, potassium 2-propoxide was in all cases less effective than potassium hydroxide.

Catalytic efficiency of the metal carbene complexes is much higher than of the benzimidazolium salt 10. Comparison of TON and TOF for the catalysts 11, 14, 17a,b, 20 at concentrations of 0.1 mol% showed that efficiency of the nickel complex 14 is noticeably lower than that of the copper complex 11 and the nickel and palladium chelate complexes 17a,b (compound 14 was partially decomposed with formation of a metallic nickel in the course of reaction). Palladium complex 20 efficiently catalyzes the reaction during first minutes of the process. A complete catalyst deactivation occurred at approximately 75 % conversion.

For highly catalytically effective compounds 11, 17a,b, 22, it was possible to perform a comparison of the TON and TOF values at a lower concentration (0.01 mol%). For the monocarbene complex 11 and chelate complexes 17a,b the indexes TON and TOF were close, but the most effective was the palladium chelate complex 17b. copper(1) biscarbene complex 13 and the polymeric carbene complex 22 were even more effective .

TON and TOF values are maximum for compounds 13 and 22 at concentrations of 0.001 mol%, whereas for the polymeric catalyst 22 (Exp. No. 19) these values are slightly higher than for the complex 13 (Exp. No. 18). For the most active rhodium(III) carbene complex 9 they were noticeably increased in both cases in reaction with the related benzophenone (TON 10580, TOF 441 h–1). TON value for the complex 9 is lower than that for compounds 13, 22, but the difference in TOF values is especially high due to the long reaction time using the known catalyst 9 (up to 24 h) with yields not higher than 86 %. Almost quantitative yields of the compound 25 (Exp. No. 14, 17) were observed in case of catalysis with complexes 13, 22 during 2 hour of the reaction time.

Benzophenone 24 at the catalyst concentration of 0.001 mol% was reduced analogously with formation of benzhydrol 26 with high TON and TOF values comparable with those for the ketone 23 reaction.

It should be noted that the inorganic copper halogenides (CuCl, CuI) are considerably less active than their heterocyclic carbene complexes. Reaction completion in these cases could not be reached even using 10 mol% catalyst concentrations.

The probable mechanisms of the ketone catalytic reduction with 2-propanol in the presence of potassium hydroxide are presented below (Scheme 7).

Scheme 7
scheme 7

 

Mechanism of the reduction of carbonyl compounds with alcohols catalyzed by metal carbene complexes is evidently similar to the effect of aluminum isopropoxide in the Meerwein-Ponndorf-Verley reaction. Moreover, for the carbene complexes, first a halogen ion exchange for an alkoxide ion probably happens, whereas the alkoxide ion is formed in equilibrium from potassium hydroxide and isopropanol (Equation 1), with formation of a metal complex alkoxide (Equation 2). Further, analogously to the Meerwein-Ponndorf-Verley reduction, an interaction of the carbonyl compound with the vacant d-orbital of the metal and a hydride transfer from alcoholate group to the carbonyl carbon atom in a cyclic transition state occurs (Equation 3).

Similarly, in chelate complexes 17a,b, a displacement of phenolate ion from the metal coordination sphere with subsequent restoration of the chelate structure and acetone formation may occur. However, another way is also possible, proposed earlier in [32], where a metal hydride acts as an intermediate (Equation 4), which reduces the multiple carbonyl bond (Equation 5). This reaction direction was confirmed by transition metal hydrides isolation in some cases [3].

Thus three classes of catalysts of the hydride transfer from 2-propanol to ketones have been found – carbene complexes of copper(I), nickel, and palladium, and also carbenes, which are, however, less effective. It is essential that copper (I) complexes are substantially more effective than the known rhodium, iridium and ruthenium complexes. The most effective catalyst proved to be the copper(I) carbene polymeric complex. Copper(I) biscarbene monomeric complex was of the similar efficiency.

Experimental

1 H and 13 C NMR spectra were recorded on Gemini 200 and Bruker Avance II 400 spectrometers with TMS as internal standard. Purity of substances was monitored by TLC on Silufol plates with a 10:1 CHCl3–MeOH mixture.

Molecular properties of polymer 22 were studied on the measurement complex for Du Pont liquid chromatography, fitted with bimodal Zorbax PSM-100 and 1000 columns, each of which can be linearly calibrated in molecular mass from 102-106. Chromatograph was calibrated using Du Pont PS polysterene standard with molecular masses of Mw 1000, 50000 and Mw/M n  = 1.01. Oligomer coming out of the column was detected by an ultraviolet detector set to 282 nm wave length. DMF purified and dried according to the standard methods was used as eluent. Analyses temperature was 25°C and the flow rate was 0.7 ml/min. System pressure was equal to 53– 55 bar. Error of the retention time detection was ±1 %. To determine the amount of high- and low-molecular mass fractions, after the sample coming out from the column and signal recording using MO Spectra Physics software program the peak area ratios were calculated for peaks which correspond to each component with certain average molecular mass. Molecular properties of the polymer 22 were calculated using Chrom I Insoftus software program [33]. The method was used for molecular mass determination of polar substances, including polyelectrolites [3335]. Elemental analysis for metal content was carried out along with carbon, hydrogen and halogen contents measurement using dry oxides residue after sample combustion.

(1,3-Dibenzylbenzimidazol-2-ylidene)copper(I) Chloride (11). A mixture of 1,3-dibenzylbenzimidazolium chloride (10) (1.0 g, 3.0 mmol) and copper(I) chloride (0.3 g, 3.0 mmol) was dissolved in dry MeCN (15 ml), Et3N (0.5 ml, 3.6 mmol) was added, and the mixture was boiled for 2 h. Then more Et3N (0.5 ml, 3.6 mmol) was added, and refluxing was continued for 30 min. The reaction product was precipitated with water, filtered off, washed with a 1:3 2-PrOH–petroleum ether mixture, and dried over KOH. Product 11 (1.05 g, 84 %) was recrystallized from MeCN. Yield 0.7 g (56 %); mp 175-177 °C. 1 H NMR spectrum (200 MHz, CDCl3), δ, ppm: 5.76 (4 H, s, 2CH2N), 7.24-7.54 (14 H, m, H Ar). 13 C NMR spectrum (50 MHz, CDCl3), δ, ppm: 51.2 (CH2N); 111.8, 123.4, 127.3, 127.7, 128.5 (C Ar); 133.4, 136.3 (i-C Ar); 188.6 (C-2). Found, %: C 63.61; H 4.64; Cl 8.59; Cu 15.92; N 7.24. C21H18ClCuN2. Calculated, %: C 63.47; H 4.57; Cl 8.92; Cu 15.99; N 7.05.

Bis(1,3-dimethylbenzimidazol-2-ylidene)copper(I) Iodide (13). A mixture of 2-cyanomethyl-1,3-dimethyl-2 H-benzimidazoline (12) (2.55 g, 13.6 mmol) and copper(I) iodide (1.30 g, 6.8 mmol) in MeCN (5 ml) was refluxed for 2 h. The precipitate was filtered off, washed with a small amount of MeCN, and dried. Yield 2.20 g (67 %); mp. 220-221 °C (MeCN). 1 H NMR spectrum (200 MHz, DMSO-d6), δ, ppm: 4.06 (12 H, s, 4CH3); 7.40 (4 H, m, H Ar); 7.65 (4 H, m, H Ar). 13 C NMR spectrum (50 MHz, DMSO-d6), δ, ppm: 34.3 (CH3); 110.9 (C-4,7); 123.0 (C-5,6); 134.0 (i-C Ar); 190.7 (C-2). Found, %: C 44.53; H 4.14; Cu 13.38; I 26.51; N 11.44. C18H20CuIN4. Calculated, %: C 44.78; H 4.18; Cu 13.16; I 26.28; N 11.60.

Bis(1,3-dimethylbenzimidazol-2-ylidene)nickel Dichloride (14). 2-Cyanomethyl-1,3-dimethyl-2 H-benz-imidazoline (12) (0.95 g, 5.08 mmol) in MeCN (6 ml) was added to a suspension of NiCl2(PPh3)2 (1.66 g, 2.54 mmol) in MeCN (4 ml) and the mixture was refluxed for 2 h. The precipitate was filtered off, washed with ether, and dried. Yield 1.07 g (100 %); mp 275-278 °C (MeCN). 1 H NMR spectrum (200 MHz, DMSO-d6 + Py-d5), δ, ppm: 4.47 (12 H, s, 4CH3), 7.30-7.78 (8 H, m, H Ar). 13 C NMR spectrum (200 MHz, DMSO-d6 + Py-d5), δ, ppm: 35.7 (CH3); 110.4, 123.8 (C Ar); 134.9, 144.2 (i-C Ar); 180.6 (C-2). Found, %: C 51.35; H 4.76; Cl 16.67; N 13.15; Ni 14.07. C18H20Cl2N4Ni. Calculated, %: C 51.23; H 4.78; Cl 16.80; N 13.28; Ni 13.91.

Bis-(1- tert -butyl-2-(2-oxidophenyl)-3-phenyl-1,2,4-triazol-5-ylidene)palladium (17b). The salt 15b (0.23 g, 0.62 mmol) and Pd(OAc)2 (0.07 g, 0.31 mmol) were dissolved in a mixture of THF (10 ml) and DMSO (0.5 ml), heated at 50 °C and stirred for 2 h. MeOH (10 ml) and Na2CO3 (0.26 g, 2.48 mmol) were added and the mixture stirred for 1 h. The reaction mixture was poured into water (50 ml). The precipitate was filtered off and dried. The precipitate was dissolved in CH2Cl2 (10 ml) and filtered through a thin layer of silica gel. The solution was evaporated to dryness. Yield 0.13 g (62 %); mp 140 °C (PhMe). 1 H NMR spectrum (200 MHz, CDCl3), δ, ppm: 1.60 (18 H, s, 2(CH3)3 C); 7.31-7.56 (18 H, m, H Ar). 13 C NMR spectrum (100 MHz, CDCl3), δ, ppm: 30.8 (CH3); 62.6 ((CH3)3C); 114.6, 121.4, 124.4, 128.5, 128.6, 129.4, 130.2 (C Ar); 126.9 (i-C Ph); 148.2 (i-C 2-oxydophenyl); 153.0 (C-3); 161.7 (C–O); 171.1 (C-2). Found, %: C 62.72; H 5.07; N 12.39; Pd 15.24. C36H36N6O2Pd. Calculated, %: C 62.56; H 5.25; N 12.16; Pd 15.40.

Bis[4-(4-bromophenyl)-1- tert -butyl-3-phenyl-1,2,4-triazol-5-ylidene]palladium Dichloride (20). 4 (4-Bromophenyl)-1-tert-butyl-3-phenyl-1,2,4-triazol-5-ylidene (19) [30] (0.20 g, 0.56 mmol) in THF (1 ml) was added to a suspension of palladium chloride (0.05 g, 0.28 mmol) in MeCN (1 ml) and stirred for 30 min. The precipitate was filtered off and dried to give compound 20 (0.15 g); a further 0.1 g of complex 20 was obtained from the mother liquor by evaporation. Overall yield 0.25 g (100 %); mp 160-163 °C (MeCN, subl.). 1 H NMR spectrum (200 MHz, DMSO-d6), δ, ppm: 1.64 (18 H, s, 2(CH3)3 C); 7.26-7.67 (18 H, m, H Ar). 13 C NMR spectrum (50 MHz, DMSO-d6), δ, ppm: 30.1 (CH3); 62.9 ((CH3)3C); 127.8, 128.6, 128.7, 129.1, 130.4, 131.6, 132.4, 132.9 (C Ar); 143.2 (i-C Ar); 151.4 (C-3); 171.0 (C-2). Found, %: C 48.61; H 3.96; Br 18.26; Cl 8.05; N 9.37; Pd 11.75. C36H36Br2Cl2N6Pd. Calculated, %: C 48.59; H 4.08; Br 17.96; Cl 7.97; N 9.44; Pd 11.96.

Polymer of 1,1',3,3'-Bis(3-oxa-1,5-pentylene)bis(benzimidazole-2-ylidene)copper(I) Iodide (22). Copper(I) iodide (0.66 g, 3.4 mmol) in absolute MeCN (15 ml) was added dropwise with constant stirring in an atmosphere of nitrogen at room temperature to a solution of 1,1',3,3'-bis(3-oxa-1,5-pentylene)bisbenzimidazolinium diacetylacetonate (21) [31] (2.00 g, 3.4 mmol) in absolute MeCN (30 ml). The reaction product began to crystallize from the solution. After addition of all of the copper(I) iodide, the mixture was kept at room temperature for 40 min. The precipitate was filtered off and washed on the filter with ether in an atmosphere of nitrogen. The crystals of complex were greenish in appearance. Yield 1.60 g (82 %); mp 164-165 °C. 1 H NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 3.82 (8 H, s, 4CH2O); 4.30-4.70 (8 H, m, 4CH2N); 6.60-7.95 (8 H, m, H Ar). 13 C NMR spectrum (100 MHz, in solid state), δ, ppm: 48.3 (CH2O); 69.4 (CH2N); 112.0, 123.9, 130.5, 134.0 (C Ar); 142.8 (i-C Ar); 154.8, 164.9 (C-2). LC: Mw 43700; M n 42400 (M w /M n =1.03). Found, %: C 46.89; H 4.31; Cu 11.34; I 22.42; N 9.44. C22H24CuIN4O2. Calculated, %: C 46.61; H 4.27; Cu 11.21; I 22.39; N 9.88.

General Method for the Reduction of Compounds 23, 24 and Control of the Reaction of. 0.1 M KOH solution (10 mmol) in 2-PrOH and a small amount of a catalyst (Table 1) were added to ketone 23 or 24 (2 mmol). The reaction mixture was refluxed and monitored by TLC. Quantitative analysis of the starting material and the reduction product during the reaction time was carried out as follows: 2-PrOH was evaporated until crystallization of the remaining starting material began (a volume of about 3 ml), cooled, and the residue was filtered off. Because of the very low solubility of the ketone in alkaline solution, the ketone did not remain in the mother liquor (TLC monitoring). Water (12 ml) was added to the mother liquor, and the precipitate of the carbinol 25 or 26 was filtered off, dried, and the yield of product determined. Estimation of the purity of the compound isolated was determined TLC and 1 H NMR spectroscopy.

This work was carried out with financial support of the State Fund of Fundamental Investigation of the Ministry of Education and Sciece of Ukraine (grant No: F28.003), Ukraine National Academy of Sciences (grant 24.03.10), and the Russian Foundation for Fundamental Investigations (grant 10.0390418-Ukr_a).