Highly efficient carbene and polycarbene catalysis of the transesterification reaction

Highly efficient carbene and polycarbene catalysis of the transesterification reaction of ethyl benzoate in methanol has been observed and results in values of TON as high as 4000 – 6150 at a molar ratio of ester to methanol of 1:18 at room temperature. The most effective catalysts were found to be the individual carbenes or in situ generated carbenes, namely adamantyl and aromatic substituted cyclic compounds and polymeric carbenes. None of the reactions requires the use of molecular sieves. The polymeric imidazol-2-ylidene catalyst was used for the efficient production of biodiesel fuel from sunflower oil.


Introduction
The transesterification reaction is one of the mildest and most effective methods for the preparation of esters. 1 However, the traditional catalysts are either insufficiently effective due to their basic nature or cause corrosion of the metallic equipment (inorganic acids).3][4][5][6][7][8] The latter reaction is typically carried out at room temperature in the presence of 0.5-5.0mol% of carbenes and molecular sieves.The efficiencies of the catalysts can be estimated on the basis of the values of TON and TOF.TON is a turnover number that means a number of catalytic cycles made (the ratio of a mol number of the product to a mol number of the catalyst).TOF is a turnover frequency that means a number of catalytic cycles per a unit of time, the most often per one hour (TON per a unit of time).In the case of reactions that are catalysed by imidazol-2-ylidenes and their 4,5-dihydro analogues, the TON values typically fall in the range of 20-60, TOF 30-220 h -1 . 2 However, larger values of 200 and 2300 respectively have been observed for the reactions of vinyl esters due to the irreversibility of the acetaldehyde release process. 4he transesterification reaction serves as an important tool for the production of biodiesel fuel.In the latter case the reaction is carried out in an excess of alcohol.To the best of our knowledge, there has only been one attempt to carry out a similar catalytic process using carbenes on a model compound. 3In this paper the transesterification of methyl benzoate with ethanol and isopropanol in a 1:20 molar ratio was carried out in the presence of 3.6-4.4mol% of 1,3-disubstituted imidazol-2-ylidenes and resulted in 79-85% yields of ethyl esters (TON 17-19, TOF 1 h -1 ).
The catalytic activities of other classes of stable carbene have not been studied yet.
The goal of the present work was to study the catalytic properties of a variety of types of stable carbenes for use in transesterification reactions.
It was particularly important taking into account moderate or low efficiences of carbenes in many other organic reactions (in most cases TON is no more than 100). 9,10

Preparation of carbenes and precarbenes
Ethyl benzoate was used as the model compound for the transformation to methyl benzoate in the presence of a catalyst in methanol solution (Scheme 1).The stable carbenes 1-11 were used as catalysts for this reaction (Schemes 1 and 2), and were generated in situ from the corresponding azolium salts (BH + X -), or alternatively used as individual compounds (1a, 2d, 3c, 7).The requisite compounds were the monocarbenes 1-6, the biscarbenes 7,8 and the polycarbenes 9-11.In alcohol solutions all of these compounds are in equilibrium with alkoxyazolines and H-complexes of carbenes (see, for example, the equilibrium 1 ⇄ 1A ⇄ 1B in Scheme 3).
The requisite carbenes 1-11 were generated in situ using the appropriate precarbenes (BH + X) and potassium methoxide in anhydrous methanol solution.The corresponding organic perchlorate salts were used as precarbenes.
For comparison purposes the catalysis was also studied with ammonium (12) and phosphonium (13) methoxides which together with sodium methoxide can clear up the role of alkoxide ions in catalysis.However, it should be noted that the first compound can exist in equilibrium with ammonium ylides, 11 as can the latter compound with the appropriate phosphorane 13A (Scheme 3).
Compound 11 .2НClO4 is easily soluble in polar organic solvents, such as dimethylformamide, dimethylsulfoxide and insoluble in other organic solvents.According to the liquid chromatography data the polymer 11 .2НClO4 has a narrow molecular weight distribution (Mw 68800; Mn 63100; Mw / Mn = 1.09; naver = 257).The low degree of polydispersity of the polymer is also confirmed by the narrow single signals in the 1 H NMR spectrum.Particularly, there are narrow signals of methylene (δ 5.44 ppm), aromatic protons (δ 7.50 -7.78 ppm) and meso-protons (C 2 H) of the imidazolium ring (δ 9.37 ppm).
It should be noted that the polymeric salt 10 .2НClO4 has conjugated fragments and a monomeric unit comprises two carbenoid centers unlike the polyxylyleneimidazolium polymer 11 .2НClO4 that includes only one carbenoid center in a monomeric unit.
The singlet proton signals for polymeric salts 9 .2НClO4 and 10 .2НClO4 are expressed rather clearly.The signals of methylene group (δ 5.95 ppm), aromatic proton and pyridinium phenylene nuclei (δ 7.70 -8.73 ppm) were found in the spectrum of the polymer salt 9 .2НClO4 along with C 2 H-signals of the pyridinium nuclei that are shifted downfield (δ 9.33 and 9.47 ppm).The signals of meso-protons of salt 10 .2НClO4 (C 2 H) is strongly shifted downfield (δ 10.11 ppm) as compared with bisimidazolium salt 8a (δ 9.05 ppm), to a lesser extent, but also shifted downfield the characteristic signals of the methylene (δ 5.58 ppm) and aromatic protons (δ 7.65 -8.44 ppm).

Catalytic results
The overall results of the catalytic transesterification of compounds 1-11 are presented in the Table .The data in the table revealed that the efficiency of a sodium methoxide in these reactions is minimal (TON 7-17, TOF 8-22 h -1 ).As a consequence a significant concentration of the catalyst and an increase in temperature are necessary for generating high yields of the product under the conditions that were selected for this experiment (the ratio of the reactants was chosen to be 1:9, 0.04 mol% of the catalyst and 4 h at room temperature).The efficiency of the triazolylidene catalysts 1a, b, 7 (either in an individual state or in an situ generated form) was found to be higher than that for sodium methoxide.The carbenes 1a and 1 b were found to be less active (TON 175-225, TOF 44-56 h -1 ) than those of the biscarbene 7 (TON 625, TOF 156 h -1 ).It is interesting to note that under identical conditions, the increase in the number of catalytic centers in one molecule of compound 7 relative to that of 1a resulted in a higher yield of methyl benzoate by almost four times (25%).In the case of the highly sterically shielded carbene with branched aromatic substituents (2d) the catalytic effect was not evident.
The efficiencies of carbenes 1 and 7 of the triazole series were found to be significantly inferior to those of carbenes 2a, 3a and 3b of the imidazole and benzimidazole series (TON 1620-1800, TOF 270-450 h -1 ).Even at loadings of 0.04 mol% for compounds 2a, 3a and 3b yields of methyl benzoate can be achieved in the region of 65-72% when exposed to room temperature for 4 hours.However, on the other hand, the arylene substituted biscarbene 8b exhibited an even higher efficiency (TON 2183, TOF 546 h -1 ), by contrast the biscarbene 8a with an aliphatic bridge is significantly lower in terms of efficiency (TON 1300, TOF 325 h -1 ).
The carbenes 9-11 were also found to be highly efficient polymeric catalysts and exhibited high TON values in the range of 2100-2350.
An additional increase in efficiency was observed for the carbenes (TON 2600-4300 and TOF 650-1075 h -1 ) using a 0.01 mol% loading and a ratio of the reagents of 1:18.In this case a series of efficiencies was evident from the values of TON and TOF,in h -1 : 3c (2600, 650) < 2b (3500, 875) < 11 (4000, 1000) < 2c (4300, 1075) Compounds 2b, c, 3c, 11 exhibited the highest catalytic efficiencies for the transesterification reaction.Moreover, in this case the method does not require the use of molecular sieves to produce high yields of the end products.Among the individual carbenes (1a, 2d, 3c, 7) compound 3c was found to have the highest efficiency (TON 6150, TOF 1538 h -1 ).
The following conclusions can be made with respect to the different factors that influence the catalytic efficiencies.
1) The largest influence on the catalytic efficiencies of the carbenes is exhibited by carbenes that feature Nadamantyl-and N-aromatic groups (even if they are not connected to a heterocyclic nucleus such as pxylylene) (2b, c, 3c, 4, 5, 8b, 10, 11).The carbocyclic aromatic carbene 6 is also very efficient.In some cases the TON values can be very large (for 3c up to 6150 cycles).The high effect of adamantyl substituted compounds 2b,c, 3c, 4, 5 can be explained by their largest nucleophilicities.For compounds 8b, 10, 11 not only carbene centers can play an important role but also their ylidic forms (being in an equilibrium).
2) The steric shielding of carbenes (for example, by the use of adamantyl groups) increases the efficiency of the catalysis.It should be recalled, however, that some results depend on the extent of steric shielding.For example, carbene 2d has a buried volume of %Vbur 53% (for the evaluation of analogues) 29,30 but, by contrast, does not show a notable catalytic effect.
3) Individual carbenes are considerably more efficient than those of the in situ generated compounds (in the case of carbene 3c by 2,6 times).Furthermore, in the latter case the efficiency is also dependent on the method that was employed for carbene generation.
The foregoing results indicate that catalyst 11 would be one of the best choices for the transesterification reaction of plant oils (esters of fatty acids and glycerol).In fact, when the catalytic green process was carried out on sunflower oil in the presence of compound 11 [0,1 mol% or 0.033 mol% for one ester function] this catalyst worked with high efficiency (TON 2667, TOF 667 h -1 ) and afforded an 88% yield of the distilled colorless mixture of methyl esters of fatty acids that are predominantly linoleic (75%) and oleic (23%), that in turn can be used in industry for the production of e.g.perfume additives or biodiesel fuel.In the latter case, only technical oils should be used (from e.g.palm, rapeseed, algae, etc.).
It should be noted that until now many catalysts have been proposed for the preparation of biodiesel fuel (as reviews see, for example, the papers [31][32][33][34] ).Among them special attention was paid to guanidine derivatives (see also [35][36][37][38] ), which having basicities close to carbenes do not form soaps during the reaction and their catalytic efficiencies are close to those for sodium hydroxide and methoxide (for 1,5,7-triazabicyclo[4.4.0]dec-5-eneTBD TON is no more than 270 at 70 C, 1 mol% of a catalyst, the molar ratio of rapeseed oil : methanol is 1:2.3).As can be seen from the data obtained in the present work carbenes are considerably more efficient (TON 2667 at room temperature, 0,1 mol% of a catalyst, the molar ratio of sunflower oil : methanol is 1:20).
The mechanism of the catalysis of the transesterification reaction by carbenes has not yet been studied in detail. 27However, the low efficiency of sodium methoxide in the reaction indicates that the role of the carbene catalyst is not limited by the reaction of alkoxide ions with the ester.The ammonium (12) and phosphonium (13) alkoxides that are generated from the corresponding salts are significantly more effective as stronger bases (TON 1150, 1575 and TOF 288, 394 h -1 , respectively) than sodium methoxide (probably due to their ylidic forms playing a part in the reaction).As a consequence, the phosphonium ylide, easily obtained from salt 13, is more effective than the ammonium ylide from salt 12.However, carbenes 2-6, 8b, 9-11 are significantly more efficient than those of the ammonium and phosphonium catalysts derived from salts 12 and 13.The increase of the efficiencies of the heterocyclic carbene catalysts relative to those of the onium ylides from 12 and 13 points to an important role of the carbene centers for catalysis, particularly multiplet ones to activate the ester molecules.
Several possible versions of the mechanism have been discussed and presented.Examples include the work described in research reports 39,40 or in monographs 9,10 .However, a common feature of these mechanisms is the participation of carbenes that are connected to alcohols by means of H-bonds such as those in 1B or in azoline forms such as 1A, with which they are in equilibrium.These particles are bonded by a carbene transfer from the alcohol component to the activated ester carbon atom and accept the leaving molecule of alcohol.

Conclusions
As a consequence of the foregoing, a highly efficient catalysis by mono-, bis-and polyheterocyclic and carbocyclic carbenes was observed for the transesterification reaction when carried out in an excess of alcohol.Furthermore, the TON and TOF indices were found to exceed significantly those of the known catalytic effect of carbenes that have close to stoichiometric quantities of the reactants in the presence of molecular sieves.They also exceed those of the known process by two orders of magnitude in an excess of alcohol.The possibility of using polymer 11 with high efficiency to produce biodiesel fuel has in fact been demonstrated in an experiment on sunflower oil.

General information
The 1 H NMR and 13 C NMR spectra were recorded using a Bruker Avance II 400 spectrometer (400 MHz for 1 H NMR spectra and 100 MHz for 13 C NMR spectra) or Gemini 200 spectrometer in DMSO-d6 or CDCl3 solutions or in the solid state.The 1 H NMR and 13 C NMR chemical shifts are reported relative to those of tetramethylsilane (TMS) (solution) and sodium 2,2-dimethyl-2-silapentan-5-sulfonate (DSS) (solid state).The thin-layer chromatography was performed on silica gel with chloroform or a 10 : 1 mixture of chloroform and methanol as an eluent, followed by development with iodine.All elemental analyses were carried out at the Analytical Laboratory of the Litvinenko Institute of Physical Organic and Coal Chemistry.The molecular characteristics of the oligomers and polymers were studied on a Du Pont device for liquid chromatography that was equipped with a set of bimodal columns Zorbax PSM-100, and 1000, each of which can give a linear calibration in the molecular weight range 102 -106.The chromatograph was calibrated with a polystyrene standard Du Pont PS with molecular weights of Mw 1,000 and 50,000 (Mw / Mn 1.01) along with a sample of the known salt 2a .НClO4.The polymer yield from the column was found by a UV sensor that was tuned to a wavelength of 282 nm.

Procedure for catalytic measurements.
The catalytic transesterification reaction of ethyl benzoate to methyl benzoate with carbenes 1-11 and onium alkoxides 12,13 were carried out in an anhydrous methanol solution (using a molar ratio of ester-methanol of 1:9 or 1:18).Molecular sieves were not used in this process.
To a solution of ethyl benzoate (3.15 mL, 22 mmol) in a methanolic solution (8 mL) of potassium methoxide (0.616 g, 0.0088 mmol) a salt precatalyst (0.0088 mmol) was added and stirred for 4 h at room temperature.Diethyl ether (30 mL) was added to the reaction solution, the organic layer was washed with water (320 mL), separated and dried with anhydrous sodium sulfate.The ether was evaporated and the residue was distilled in a vacuum.The distillate was analyzed by 1 H NMR spectroscopy on the contents of methyl benzoate and ethyl benzoate ( СН3О 3.85 ppm, ethyl benzoate  СН3С 1.34 ppm and  СН2С 4.34 ppm in CDCl3).

Table .
The catalytic properties of carbenes 1-11 and compounds 12 and 13 in the transesterification reaction of ethyl benzoate in methanol solution (molar ratio of reactants 1:9) at 23 °С a The experiment was carried out at the molar ratio ester-methanol 1:18, for 4 h at room temperature; b with individual carbene 3с; c with sunflower oil.The catalyst loading, TON and TOF are indicated on the basis of one ester group of the oil.