Medium Fluorous Separation Using Hydrofluoroether and Weakly

Research Article Cite This: ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX

pubs.acs.org/journal/ascecg

Medium Fluorous Separation Using Hydrofluoroether and Weakly Polar Solvents for Environmentally Friendly Recycling of Catalysts Jan Hošek,† Ondřej Šimůnek,† Pavlína Lipovská,† Viola Kolaříková,† Kateřina Kučnirová,† Antonín Edr,† Nikola Štěpánková,† Markéta Rybácǩ ová,† Josef Cvačka,‡ and Jaroslav Kvíčala*,† †

Department of Organic Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic

‡

S Supporting Information *

ABSTRACT: As a novel approach to the separation of polyfluorinated compounds, we disclosed that HFE 7100 (methyl perfluorobutyl ether) forms with alkanes or chlorinated solvents two-layer systems between −51 and 30 °C depending on the nonfluorinated solvent. Similarly, more fluorinated HFE 7500 (ethyl perfluoroisoheptan-3-yl ether) forms the corresponding two-layer systems between −42 and 79 °C. While fluorinated compounds bearing 40−60% of fluorine were exclusively dissolved in the hydrofluoroether layer, nonfluorinated compounds strongly prevailed in the nonfluorinated solvent. The noncoordinating and aprotic character of the solvents used, as well as their low boiling points, enabled efficient isolation and recycling of sensitive polyfluoroalkylated Hoveyda−Grubbs second-generation precatalyst analogues. This medium fluorous method was further extended to the separation of various classes of polyfluorinated compounds including reaction intermediates, ligands, and ionic liquids. The key components of the medium fluorous separation system, hydrofluoroethers, are affordable, environmentally acceptable, and easily recyclable, as well as highly tolerable by sensitive transition-metal complexes. KEYWORDS: Medium fluorous separation, HFE, Recycle, Ruthenium complex, Purification

■

INTRODUCTION The search for innovative approaches, aiming at better separation and recycling of expensive transition-metal complexes, as well as in minimizing contamination of the environment with heavy metals, led more then 20 years ago to the birth of fluorous chemistry, employing fluorophilic interactions of long fluorinated chains.1−10 Based on the fluorine content in the molecule, two main approaches emerged. In the historically first approach, heavy fluorous chemistry was invented, employing liquid−liquid separation of a highly fluorinated transition-metal catalyst, reaction product, or sideproduct and nonfluorinated compounds between perfluorinated and nonfluorinated solvent. Mild separation conditions and the aprotic character of both solvents used make this method ideal for sensitive transition-metal complexes. However, it also suffers from several drawbacks. First, for efficient separation, the fluorous partition coefficient, Pi(FBS), between perfluoro(methylcyclohexane) and toluene at room temperature, has to reach at least 20. This is mostly provided by the attachment of multiple long polyfluorinated ponytails. However, the use of fragments bearing more than six perfluorinated carbon atoms is no © XXXX American Chemical Society

longer recommended because of the persistent and adverse effects of their decomposition products on the environment.11,12 Moreover, building blocks based on more than 10 perfluorinated carbons are prohibitively expensive. Second, the above-mentioned negative issues related to environment and price also apply for perfluorinated solvents used for the separation. This can be circumvented by ommiting the perfluorinated solvent completely, precipitating the heavy fluorous complex on the walls of the flask, 13,14 but manipulations with often negligible amounts of sensitive organometallic complexes spread over a large surface can be quite tedious. In another approach, selective precipitation on the Teflon tape based on fluorophilic interaction between the Teflon surface and fluorous complex was achieved, and the catalyst was recycled.15 The limitation of this method is given by difficult control of the regularity of precipitation on the tape, as well as by potential problems with the precipitation of fluorous decomposition products of the catalyst. Received: February 22, 2018 Revised: April 3, 2018 Published: April 4, 2018 A

DOI: 10.1021/acssuschemeng.8b00865 ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX

Research Article

ACS Sustainable Chemistry & Engineering Third, the heavy fluorous system becomes homogeneous between 80 and 100 °C, temperatures which can be too high for some sensitive complexes or selective reactions. Light fluorous chemistry attempted to solve the abovementioned drawbacks, using as a separation process solid-phase extraction on polyfluoroalkylated silica. For efficient separation, the attachment of only one perfluoroalkyl chain is normally sufficient with fluorine content typically below 40%.16−18 The use of common nonfluorinated solvents for the separation represents another huge advantage of light fluorous chemistry. While this approach is synthetically much more feasible and cheaper, it still suffers from two main drawbacks: First, because of the high price of fluorous silica, it is not easily scalable and the quality of the recycled fluorous silica slowly deteriorates over the number of separation cycles. Second, the fluorophobic wash employs protic solvents such as water or methanol, which are often not tolerable by sensitive homogeneous catalysts. Both these factors prevented the application of this separation approach in common use. The need to use expensive fluorous silica was avoided in the medium fluorous approach of Matsugi et al., who employed medium fluorous (i.e., containing 40−60% of fluorine) Mukaiyama reagent modified with one long (C 10 F 21 ) perfluorinated chain for efficient amide coupling.19 The medium fluorous side product of the reaction could then be efficiently separated after addition of water to the reaction mixture, precipitation, and filtration. Although this approach removes the drawback of the light fluorous chemistry consisting of poor scalability due to the use of expensive fluorous silica, the other disadvantage, connected with the use of protic solvents, persists. This was clearly confirmed in the attempted recycling of medium fluorous Hoveyda−Grubbs secondgeneration precatalyst analogue reported recently by Matsugi.20 Although the gross mass of the recycled precatalyst remained unchanged, its activity significantly decreased after three catalytic cycles even for easily proceeding ring-closing metathesis of N-tosyldiallylamine. Ruthenium-based Grubbs and Hoveyda−Grubbs complexes are highly efficient precatalysts of alkene metathesis, a highly efficient approach for the construction of novel organic molecules.21,22 However, ruthenium complexes are quite expensive and, moreover, they are highly toxic and their removal from reaction products often represents a difficult task. Hence, several strategies for their removal from the reaction mixtures, and, even better, recycling, have been developed,23 e.g., recycling of the precatalysts by column chromatography, covalent immobilization on polymer support, covalent or noncovalent immobilization on mesoporous silica, or the use of a two-phase homogeneous system based on ionic liquids or nonmiscible solvents. However, most of the recycling methods have significant drawbacks as lowering the catalyst activity or more rapid decomposition of the active catalytic form over time because of the use of less compatible solvents. Grubbs and Hoveyda−Grubbs second-generation precatalysts (G2 and HG2) belong to the most attractive targets for fluorous modificatons because of their high catalytical activity and, in the latter case, a high stability that enables purification by column chromatography.10 Fluorous modifications concentrated on three possible positions, each with some pros and cons (Chart 1). Thus, fluorous modifications of the tricyclohexylphosphine ligand of the G2 precatalyst with polyfluoroalkylated phosphines or pyridines resulted in precatalysts with high activation rate in

Chart 1. Possible Fluorous Modification of Hoveyda− Grubbs Second-Generation Precatalyst

heavy fluorous two-phase media, but the ligands could not reattach for successful recycling.24−26 Although similar modifications of the alkoxybenzylidene ligand of the HG2 precatalyst with per- or polyfluoroalkyl groups enabled light fluorous recycling, the need for reattachment of the fluorous ligand, as well as the use of protic solvents in the fluorophobic wash, resulted in a drop in catalytic activity after a few cycles.20,27−30 Substitution of the chloride ligands of the HG2 precatalysts for perfluoroalkanoates mostly resulted in insufficient fluorophilic properties and a significant drop in activity.31 However, the use of more fluorophilic perfluoropolyoxalkanoates in combination with the modification of the alkoxybenzylidene ligand resulted in precatalysts with sufficient fluorophilicity for heavy fluorous recycling.32 Still, the catalytic activity remains the issue; hence, the modifications of the NHC ligand of the HG2 catalyst promise superior properties compared to the previous two modifications. However, they are also the most difficult, because the attachment of the NHC ligands requires sufficient stability of the corresponding free carbene. Thus, NHC ligands bearing linear33,34 or branched35 aliphatic polyfluorinated chains could be employed for the synthesis of Ag or Pd complexes, but their attachment to Ru complexes failed. 1,3-Dimesityl-imidazolidinylidene ligand thus emerged as the optimal target for fluorous derivatization. Although ruthenium-based alkene metathesis precatalysts bearing a polyfluoroalkylated NHC ligand are quite rare,36 we succeeded in the synthesis of the fluorous NHC ligand modified both at the heterocyclic ring and in the mesitylene substituents. Futhermore, we combined the fluorous NHC modification with the former two and obtained a small library of six light to heavy fluorous ruthenium precatalysts, 1a−1c and 2a−2c (Chart 2).37,38 With the library of light to heavy fluorous ruthenium precatalysts in hand, we were ready to search for the optimal recycling strategy after metathesis experiments.

■

RESULTS AND DISCUSSION Typical model metathesis experiments exploit ring-closing metathesis (RCM) of substituted diethyl malonates. RCM of diethyl diallylmalonate (DEDAM) proceeds easily even with low-active precatalysts leading to cyclopent-3-ene-1,1-dicarboxylates with a disubstituted double bond. In contrast to that, RCM of diethyl allylmethallylmalonate (DEAMM), forming a cyclopentene derivative with a trisubstituted double bond, is more demanding with optimal reaction temperatures between 30 and 40 °C and is thus mostly used for testing of complexes B


Research Article

ACS Sustainable Chemistry & Engineering with activity similar to that of commercial precatalysts. For commercial precatalysts, RCM of diethyl dimethallylmalonate (DEDMM) forming a tetrasubstituted double bond represents a critical process requiring higher temperatures above 80 °C with conversions typically not exceeding 40%. Unfortunately, most of the precatalysts displayed too low fluorophilicity to be recycled by a heavy fluorous approach. We hence extended the library of our precatalysts by three new precatalysts, 1d−1f, bearing four or five polyfluoroalkyl both in the NHC and in the alkoxybenzylidene ligands. Because we inferred that the −CF2−CH2− linker could be a potential source of instability, we substituted in precatalysts 1e and 1f the linear C6F13C2H4 substituents with more stable tertiary C5F11C(CH3)2 substitutents, which could be obtained by defluoromethylation of perfluorohexyl substituent Me3Al (see the Supporting Info) (Chart 2). Standard fluorous partition

Figure 1. Precatalysts 1c and 1d in solvent mixtures at various temperatures.

such as MeCN, DMF, or alcohols.39−41 In contrast to perfluorinated solvents, they are regarded to be environmentally acceptable,12,42 and because of their large-scale industrial production as cleaning or heat-transfer liquids, they are also quite affordable. Unfortunately, the tolerance of ruthenium alkylidene complexes to highly polar aprotic and protic solvents is rather low, and this is probably the main reason why previous attempts to recycle fluorous Hoveyda− Grubbs precatalyst analogues succeeded only partially.19,27−29 In the pilot experiments, we quite surprisingly found that HFE 7100 has limited solubility in CH2Cl2 at temperatures below −20 °C. CH2Cl2 belongs to the most tolerable solvents for Grubbs and Hoveyda−Grubbs precatalysts. Moreover, HFE 7100 has significantly less coordinating power than common ethers such as THF (which is not well-tolerated by ruthenium complexes) and can thus be employed as a cosolvent in alkene metathesis without loss of catalytic activity. In contrast to perfluoro(methylcyclohexane), it dissolves well-fluorinated ruthenium complexes 1 and 2. Using a solvent mixture HFE 7100/CH2Cl2, we were thus able to recycle catalyst 1c for five consecutive cycles without loss of activity, employing the fact that leaching of 1c into CH2Cl2 at −50 °C was minimal (Figure 1).37 Encouraged by this, we also tested other fluorinated precatalysts 1 and 2 in the moderately demanding model RCM of DEAMM (Scheme 1).

Chart 2. Ruthenium Precatalysts Bearing Fluorous NHC Ligands and Their Fluorine Content and Fluorophilicities

coefficients Pi(FBS) between perfluoro(methylcyclohexane) and toluene at 25 °C showed that 1a and 1b are light; 1c, 1e, 2b, and 2c are medium; and 1d, 1f, and 2a are heavy fluorous precatalysts. It is quite characteristic that the fluorophilicity patterns do not exactly follow the fluorine content: while the perfluoroether unit generally enhances the fluorophilicity as was observed earlier,32,34 branching and the presence of hydrogen in the fluorinated chain decrease it. Hence, most of the precatalysts displayed too low fluorophilicity to be recycled by heavy fluorous approach. When testing one of the most fluorinated precatalysts, 1d, in heavy fluorous recycling, we encountered another problem. Our standard testing reaction, ring-closing metathesis of diethyl allylmethallylmalonate, optimally proceeds at 30−40 °C. However, the standard heavy fluorous solvent mixture, perfluoro(methylcyclohexane)/toluene, still consists of two layers even at 80 °C and becomes homogeneous only at 100 °C (Figure 1). Under these conditions, however, the precatalyst 1d is not sufficiently stable, which leads to the decrease of conversion of starting diene and decomposition of the catalyst. Looking for possible solutions, we found that hydrofluoroethers such as HFE 7100 (methyl perfluorobutyl ether) of HFE 7500 (ethyl perfluoroisoheptan-3-yl ether) have been reported to form two-layer systems with highly polar solvents,

Scheme 1. Model RCM Experiments with Precatalysts 1 and 2

After each catalytic cycle, the mixture was cooled to −50 °C; the upper layer was removed; fresh substrate and CH2Cl2 were added, and the mixture was heated back to 30 or 40 °C. The results of recycling experiments for individual precatalysts are listed in Table 1. The least fluorinated precatalyst 1a significantly leached into the CH2Cl2 phase, which was accompanied by a quick loss of catalytic activity of the recycled precatalyst. This was, to a much lesser extent, also observed for precatalyst 1b, while for the other fluorinated precatalysts, the leaching was negligible. Quite surprisingly, catalytic activity of precatalysts 1e and 1f bearing tertiary fluorinated groups was significantly lower because of significantly lower activation rate. After 20 h, full conversion could be achieved for all 1 catalysts except 1d (Figure 2). C


Research Article

ACS Sustainable Chemistry & Engineering

separated HFE 7100 phase with an external standard. The analysis of the reaction mixture of RCM of DEAMM, catalyzed by precatalyst 1c, showed that the recycled material both after the first and after the fifth cycle is practically pure precatalyst. Because the reaction rate of the formation of metathesis product remained nearly constant over all five cycles,17 the recycled precatalyst 1c is probably reformed by the release− return mechanism (Figure 4).

Table 1. Recycling Experiments with Precatalysts 1 and 2 cycle/conversion (%)

a

precatalyst

1

2

3

4

5

1aa 1ba 1ca,b 1da 1ea 1fa 2bc 2cc

99 99 86 96 52 35 100 86

99 97 85 87 52 37 95 98

77 95 85 87 54 14 93 90

50 92 84 88 54 12 94 91

12 90 81 89 40 20 − −

30 °C/1 h. bRef 37. cRCM of DEDAM at 40 °C/1 h.

Figure 2. Kinetics of RCM of DEAMM (0.15 M solution) catalyzed with complexes HG2 or 1 (1H NMR, CD2Cl2, 30 °C, 5%mol of catalyst).

Figure 4. 1H NMR spectra of recycled precatalyst 1c after the first and fifth cycle of RCM of DEAMM with enlarged area of the benzylidene carbene proton.

Slowly activating precatalyst 1e proved to be suprisingly active in the highly demanding RCM of DEDMM, where its activity surpassed that of HG2 and reached nearly total conversion of diethyl dimethallylmalonate after 24 h at 110 °C. On the other hand, precatalysts 1c and 1d bearing the linear polyfluoroalkyl chain gave lower conversions due to expected lower stability at high temperatures (Figure 3). In contrast to precatalysts anchored to polymeric or inorganic support, our approach using the two-phase HFE 7100/CH2Cl2 system enabled direct analysis of the recycled precatalysts by a simple 1H NMR measurement of the

We next attempted to find the scope and limitations of the two-phase systems based on HFE 7100 and HFE 7500 and especially the temperatures of the formation of the two layers (Tables 2 and 3). In both tables, colors are employed to distinguish between fully soluble mixtures (blue), two-phase systems with limited compatibility with ruthenium complexes (red), and benign solvents mixtures (green). The results are in some cases quite surprising and show that simple solvent parameters such as polarity cannot be used for satisfactory explanation of the solubility pattern. Especially remarkable are the solubility differences between ethereal and chlorinated solvents, solvents of similar moderate polarity. While ethers are in general very good solvents for HFEs, chlorinated solvents as dichloromethane or 1,2-dichloroethane are, on the other hand, poor solvents for HFEs and thus ideal candidates for medium fluorous separation of polyfluorinated compounds or transition-metal complexes bearing more than 40% of fluorine. Moreover, chlorinated solvents also belong to the most efficient and benign solvents for alkene metathesis. Thus, an appropriate combination of HFE and chlorinated solvent enables us to set the target separation temperature of medium fluorous separation to a wide range of temperatures between −50 and 80 °C. To find more exactly how much precatalyst is leaching into the organic layer, the two-layer system obtained after the first cycle of the metathesis of DEAMM catalyzed by the complex 1c (Figures 2 and 4) was cooled to three different

Figure 3. Kinetics of RCM of DEDMM (0.15 M solution) catalyzed with complexes HG2 or 1 (1H NMR, toluene-d8, 110 °C, 5%mol of catalyst). D


Research Article


temperatures, −20, −50, and −78 °C. At each temperature, 0.5 mL of the dichloromethane layer was removed and evaporated and the content of ruthenium was estimated by inductively coupled plasma mass spectrometry. For comparison, the same experiment was performed with commercial nonfluorinated HG2 precatalyst. Moreover, in a parallel experiment, the reaction mixture after the third cycle was analogously cooled to −50 °C, and the Ru content was similarly estimated (Table 4).

Table 2. Miscibility of HFE 7100 with Organic Solvents

Table 4. Leaching of Precatalyst 1c into the Dichloromethane Phase after Medium Fluorous Separation at Various Temperatures after First Cycle of RCM of DEAMM

a

separation temperature (°C)

Ru (μg)

leaching (%)

HG2 1c 1c 1c 1ca

−20 −20 −50 −78 −50

127 13.9 1.6 1.4 2.3

84 9.1 1.1 0.9 1.5

After the third cycle.

While the dichloromethane layer contained nearly all nonfluorinated precatalyst HG2 (the remaining 16% of Ru probably precipitated from the solution after the catalyst decomposition or went to the fluorous layer because of incomplete solvent separation), only ca. 9% of the fluorinated precatalyst 1c was found in the organic layer after separation at −20 °C, which finally dropped to less than 2% after separation at −50 °C or lower temperatures. We found that medium fluorous separation can be used with advantage not only for the recycling or ruthenium-based alkene metathesis catalyst but also for efficient and waste-free purification of fluorinated products and intermediates. After cooling and separation of the layers, the product solution in HFE is simply evaporated on RVO with cooling of the solvent receiver. The HFE is typically recycled by washing with water to remove volatile polar admixtures, dried, and fractionally distilled. The recovery of HFE typical reaches around 80%. Several examples of the medium fluorous separation are listed below. 3,5-Bis(polyfluoroalkylated) pyridines contaning perfluorooctyl groups have been recently employed for the preparation of fluorous G2 precatalyst analogues26 using Negishi27 or Heck28 coupling with 35% or 39% yield, respectively. Both procedures required column chromatography separation. In continuation of our search for new medium or heavy fluorous PEPPSI catalyst analogues,34,35 we synthesized analogous fluorous pyridine 3 containing two shorter perfluorohexyl groups by Negishi coupling in 35% yield without the need of chromatography by medium fluorous separation using a HFE 7500/1,2-dichloroethane solvent mixture (Scheme 2). In the search for chiral fluorous diamines as precursors of chiral NHC ligand-bearing precatalysts, the key step is the Heck reaction of bromoiodocumene 4. The reaction did not give full conversion, and moreover, bis(polyfluoroalkenylated) cumene 6 was obtained together with the target product 5 (Scheme 3). Because of close retention factors of compounds 4−6, column chromography gave poor yields of the target cumene 5. However, fluorous extraction of 1,2-dichloroethane solution of the crude reaction mixture at −20 °C with HFE 7500 afforded a solution of fluorinated cumenes 5 and 6, from which pure less

a

Phases not fully separated. bPhases not fully separated because of similar densities of solvents. cOnly one phase after melting.

Table 3. Miscibility of HFE 7500 with Organic Solvents

a

catalyst

Phases not fully separated because of similar densities of solvents.

E


Research Article

ACS Sustainable Chemistry & Engineering Scheme 2. Synthesis of Bis(polyfluoroalkylated) Pyridine 3 as a Ligand for Fluorous PEPPSI Precatalyst Analogues

Chart 3. Previously Synthesized Fluorous Imidazolium Salt 7 and New Pyrrolidinium Salt 8

MeCN was first 6 times extracted with pentane to remove all unpolar admixtures. The crude product was then evaporated, dissolved in 1,2-dichloromethane, and extracted 3 times with HFE 7500, with cooling the mixture to −20 °C and separation after each cycle. Final evaporation of the combined fluorous layers gave pure target pyrrolidium salt 8 (Figure 6).

Scheme 3. Synthesis of Bis(polyfluoroalkenylated) Cumene as an Intermediate for NHC Ligands of Fluorous Precatalysts

Figure 6. 1H NMR spectrum of crude a purified ionic liquid 8.

fluorous target cumene 5 was obtained by 6-fold roomtemperature extraction with 1,2-dichloroethane (Figure 5).

To conclude, we developed for the isolation of polyfluoroalkylated compounds, as well as for the recycling of polyfluoroalkylated transition-metal complexes, a new medium fluorous separation approach, which is highly tolerable to sensitive substances. In contrast to environmentally disadvantageous perfluorinated solvents, the method uses environmentally tolerable hydrofluoroethers with very low ODP and GWP in combination with volatile chlorinated solvents or alkanes. A detailed search for the usable combinations of solvents and separation temperatures enabled us to apply the medium fluorous separation approach in a wide range of temperatures between −20 and 80 °C. All solvents used can be easily recycled and reused in subsequent separation cycles, thus minimizing the environmental impact of the separation.

■

Figure 5. Aromatic part of the 1H NMR spectrum of fluorous separation of polyfluoroalkenylated cumene 5.

EXPERIMENTAL SECTION

Temperature data were uncorrected. NMR spectra were recorded with a Varian MercuryPlus spectrometer or with an Agilent 400-MR DDR2 spectrometer. For the Varian MercuryPlus spectrometer, 1H NMR spectra were recorded at 299.97 MHz, 13C{1H} NMR spectra at 75.44 MHz using residual deuterated solvent signals as the internal standards, and 19F NMR spectra at 282.23 MHz using CCl3F as the internal standard. For the Agilent 400-MR DDR2 spectrometer, 1H NMR spectra were recorded at 399.94 MHz, 13C NMR spectra at 100.58 MHz, and 19F NMR spectra at 376.29 MHz. Chemical shifts are given in parts per million, and coupling constants are given in hertz. Mass spectra [electrospray ionization (ESI) and atmospheric pressure chemical ionizaion (APCI)] were measured with a LCQ Fleet (Finnigan) instrument, and high-resolution mass spectrometry spectra [ESI, APCI, and fast atom bombardment (FAB)] were measured with a LTQ Orbitrap XL (Thermo Fisher Scientific) or ZAB-EQ (VG Analytical) instrument. Inductively coupled plasma mass spectrometry

In yet another project, we are searching for new hydrophobic ionic liquids containing polyfluoropolyether chains with potential applications in electrochemistry.43,44 The firstgeneration fluorous ionic liquids based on imidazolium core, e.g. 7, were not sufficiently stable, and we hence turned our attention to more stable ionic liquids based on pyrrolidinium core, e.g. 8 (Chart 3). After alkylation of N-(2-methoxyethyl)pyrrolidine with polyfluoropolyoxaalkyl nonaflate, the crude reaction mixture contained several admixtures apart from the target salt 8. Because of the highly polar nature and high boiling point, ionic liquids can be purified only with difficulty. However, combining nonfluorous and fluorous extractions gave satisfactory results. Thus, the crude reaction mixture in F


Research Article

ACS Sustainable Chemistry & Engineering analyses were obtained with a NexION 350D instrument (PerkinElmer). All reactions were performed in a dry inert atmosphere (Ar) in oven-dried flasks. In the reactions with ruthenium precatalysts, solid compounds were introduced into the reaction flasks in a glovebox. (Dichloro)(2-isopropoxybenzylidene)(triphenylphosphine)ruthenium(IV) (HG1, Hoveyda−Grubbs first-generation catalyst), potassium tert-pentoxide (1.7 M solution in toluene), and 3,5dibromopyridine were pu rchased from Sigma-Aldrich. 1, 1, 2 ,2 ,3 ,3 , 4, 4, 5 ,5 ,6 ,6 , 6- T r i d e c a fl u o r o - 8 - i o do o c t a n e a n d 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooct-1-ene were kindly donated by Atochem, and HFE 7100 and HFE 7500 were kindly donated by 3M. Ruthenium complexes 1a−1c and 2a−2c, as well as dihydroimidazolium salt 9a were obtained according to refs 37 and 38. Syntheses of the precursor of ruthenium complexes 1d−1f, polyfluoroalkylated dihydroimidazolium salt 9b, and 2-bromo-4-iodo-1-isopropylbenzene (4) are given in the Supporting Information. Diethyl allylmethallylmalonate and diethyl dimethallylmalonate (DEDMM) were prepared according to refs 45 and 46. (Dichloro)[2-isopropoxy-5(perfluorohexyl)benzylidene]-(triphenylphosphine) ruthenium(IV) (HG1F) was synthesized according to ref 29, 1-(2-methoxyethyl)pyrrolidine (10) according to ref 47, and 2,2,4,4,5,5,7,7,8,8,10,10,10tridecafluoro-3,6,9-trioxadecyl nonaflate (11) according to ref 34 (Chart 4).

solid CuCl (0.045 g, 0.45 mmol) gave complex 1e (0.279 g, 58.5%, dark green solid, mp 91.5−94 °C). [trans-1,3-Bis[2,6-dimethyl-4-(2,2,3,3,4,4,5,5,6,6,6-undecafluoro-1,1-dimethylhexyl)phenyl]-4,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)imidazolidin-2ylidene](dichloro)[2-isopropoxy-5-(1,1,2,2,3,3,4,4,5,5,6,6,6tridecafluorohexyl)benzylidene]-ruthenium(IV) (1f). According to the general procedure, salt 9b (0.503 g, 0.300 mmol), potassium tert-pentoxide (0.18 mL, 0.30 mmol), perfluorohexylated Hoveyda− Grubbs first-generation catalyst analogue (HG1F, 0.272 g, 0.250 mmol), and solid CuCl (0.040 g, 0.39 mmol) gave complex 1f (0.390 g, 70.0%, dark green solid, mp 162−163.5 °C). Study of Catalytic Activity of RCM of DEAMM or DEDMM: General Procedure. An NMR tube was charged with precatalyst (5.0 μmol, 5%mol) and solvent (CD2Cl2 or toluene-d8, 0.65 mL). The substrate [diethyl allylmethallylmalonate (25.3 mg, 0.100 mmol) or diethyl dimethallylmalonate (26.6 mg, 0.100 mmol)] was added, and the mixture was stirred at 30 or 110 °C. The progress of the reaction was monitored by 1H NMR spectroscopy. Example of Catalytic Activity Measurement of RCM of DEDMM. An NMR tube was charged with complex 1e (9.6 mg, 5.0 μmol) and toluene-d8 (0.65 mL). Diethyl dimethallylmalonate (26.6 mg, 0.100 mmol) was added, and the mixture was heated to 110 °C for 24 h, resulting in a 92% conversion rate to diethyl 3,4dimethylcyclopent-3-ene-1,1-dicarboxylate as measured by 1H NMR spectroscopy. Example of Recycling Experiment of RCM of DEAMM. A Schlenk flask was charged with complex 1c (11.9 mg, 6.0 μmol, 5%mol) and HFE 7100 (1 mL), followed by the addition of a solution of DEAMM (30.5 mg, 120 μmol) in dichloromethane (2 mL). The mixture was heated to 30 °C for 1 h and cooled to −25 °C with occasional shaking. A two-phase system was formed, and the upper layer was removed. The bottom layer was heated to 30 °C, and another portion of reactant solution (30.5 mg, 120 μmol in 2 mL of dichloromethane) was added; the whole procedure was repeated four times. For kinetic measurements, 0.7 mL of the crude homogeneous reaction mixture was transferred to a NMR tube, analyzed directly by 1 H NMR spectroscopy at 30 °C using an external standard, and then returned to the reaction mixture. Estimation of Solvent Separation Temperatures. A 2 mL vial was charged with 0.5 mL of HFE and 0.5 mL of a tested solvent. In the case of a two-layer system, the vial was slowly termostatted to higher temperatures until the solution became homogeneous. On the other hand, in the case of a one-layer system, the vial was slowly termostatted to lower temperatures until the two layers started to form. 3,5-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)pyridine (3). A two-neck flask fitted with a reflux condenser was charged with zinc granules (1.96 g, 30.0 mmol) and THF (6 mL). Then 1,2dibromoethane (398 mg, 182 μL, 2.12 mmol) was added dropwise with stirring. The resulting mixture was four times heated to reflux and cooled to rt. Then, chlorotrimethylsilane (63 mg, 74 μL, 0.58 mmol) was added dropwise. After 10 min, a solution of 1,1,2,2,3,3,4,4,5,5,6,6,6-tridecafluoro-8-iodooctane (4.7 g, 2.4 mL, 10 mmol) in dry THF (6 mL) was added slowly. The resulting mixture was stirred at rt for 30 min. A Schlenk flask was charged with Pd(PPh3)2Cl2 (0.14 g, 0.20 mmol) and 3,5-dibromopyridine (0.946 g, 4.00 mmol). Then, the solution of organozinc reagent formed in the first flask was added by cannula. The resulting yellowish mixture was stirred at 70 °C overnight. The mixture was then cooled to rt, diluted with diethyl ether (40 mL), and washed with KCN (ca. 0.1 g) in water (50 mL) and with brine (50 mL). The solution was dried with anhydrous MgSO4; the drying agent was filtered off, and the solvents were removed by a rotary vacuum evaporator, affording 2.00 g of a crude product, which was dissolved in the mixture of 1,2-dichloroethane (20 mL) and HFE 7500 (20 mL). The resulting heterogeneous mixture was stirred at rt for 1 h. The upper chloroalkane layer was removed, and the second part of 1,2-dichloroethane (20 mL) was added. The mixture was again stirred for 1 h at rt, and the upper layer was again removed; the whole procedure was once more repeated.

Chart 4. Intermediates in the Synthesis of Studied Fluorous Compounds

General Procedure for the Preparation of Ruthenium Complexes 1. A flask was charged with salt 9a or 9b and anhydrous degassed hexane (6 mL). Potassium tert-pentoxide (1.7 M solution in toluene) was added, and the resulting mixture was stirred at rt for 1 h. To the resulting brownish solution, the ruthenium complex HG1 or HG1F was added in one portion. The flask was equipped with a reflux condenser and removed from a glovebox, and the reaction mixture was refluxed for 2.5 h. Solid CuCl was added in one portion, and the resulting mixture was refluxed for another 1.5 h. The reaction mixture was then evaporated to dryness with a small amount of silica gel, and the resulting dark brown-green solid was purified by column chromatography (eluent hexane/DCM 1:1) to yield complexes 1. [trans-1,3-Bis[2,6-dimethyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-trideca-fluorooctyl)phenyl]-4,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-octyl)imidazolidin-2-ylidene](dichloro)[2-isopropoxy-5(1,1,2,2,3,3,4,4,5,5,6,6,6-tridecafluorohexyl)benzylidene]ruthenium(IV) (1d). According to the general procedure, salt 9a (0.460 g, 0.263 mmol), potassium tert-pentoxide (0.16 mL, 0.28 mmol), perfluorohexylated Hoveyda−Grubbs first-generation catalyst analogue (HG1F, 0.200 g, 0.218 mmol), and solid CuCl (0.040 g, 0.39 mmol) gave complex 1d (0.302 g, 60.2%, dark green solid, mp 78−80 °C). [trans-1,3-Bis[2,6-dimethyl-4-(2,2,3,3,4,4,5,5,6,6,6-undecafluoro-1,1-dimethylhexyl)phenyl]-4,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)imidazolidin-2ylidene](dichloro)(2-isopropoxy-benzylidene)ruthenium(IV) (1e). According to the general procedure, salt 9b (0.503 g, 0.300 mmol), potassium tert-pentoxide (0.18 mL, 0.30 mmol), Hoveyda− Grubbs first-generation catalyst (HG1, 0.150 g, 0.250 mmol), and G


Research Article


(2) Gladysz, J. A. Catalysis involving fluorous phases: Fundamentals and directions for greener methodology. In Handbook of Green Chemistry: Green Catalysis; Anastas, P. T., Crabtree, R. H., Eds.; WileyVCH: Weinberg, 2004; pp 17−38. (3) Zhang, W. Green chemistry aspects of fluorous techniquesopportunities and challenges for small-scale organic synthesis. Green Chem. 2009, 11, 911−920. (4) Gladysz, J. A. Fluorous to the core. Science 2006, 313, 1249− 1250. (5) Hobbs, H. R.; Thomas, N. R. Biocatalysis in supercritical fluids, in fluorous solvents, and under solvent-free conditions. Chem. Rev. 2007, 107, 2786−2820. (6) Pohl, N. L. Fluorous tags catching on microarrays. Angew. Chem., Int. Ed. 2008, 47, 3868−3870. (7) Fluorous Chemistry; Horváth, I., Ed.; ; Topics in Current Chemistry; Springer, 2012; Vol. 308. (8) Mika, L. T; Horváth, I. T. Fluorous catalysis. In Green Techniques for Organic Synthesis and Medicinal Chemistry; Zhang, W., Cue, B., Eds.; Wiley & Sons: Chichester, U.K., 2012; pp 137−184. (9) Pozzi, G. Fluorous catalysts. In Enantioselective Homogeneous Supported Catalysis; Šebesta, P., Ed.; RSC Green Chem. Series; Wiley & Sons, Chichester, 2012; Vol. 15, pp 159−205. (10) Fustero, S.; Simon-Fuentes, A.; Barrio, P.; Haufe, G. Olefin Metathesis Reactions with Fluorinated Substrates, Catalysts, and Solvents. Chem. Rev. 2015, 115, 871−930. (11) US EPA Long-Chain Perfluorinated Chemicals (PFCs) Action Plan (2009): http://www.epa.gov/sites/production/files/2016-01/ documents/pfcs_action_plan1230_09.pdf. (12) Lo, A. S. W.; Horváth, I. T. Fluorous ethers. Green Chem. 2015, 17, 4701−4714. (13) Wende, M.; Gladysz, J. A. Fluorous catalysis under homogeneous conditions without fluorous solvents: A “greener” catalyst recycling protocol based upon temperature-dependent solubilities and liquid/solid phase separation. J. Am. Chem. Soc. 2003, 125, 5861−5872. (14) Ishihara, K.; Kondo, S.; Yamamoto, H. 3,5-Bis(perfluorodecyl)phenylboronic acid as an easily recyclable direct amide condensation catalyst. Synlett 2001, 2001 (9), 1371−1374. (15) Dinh, L. V.; Gladysz, J. A. Catalyst-on-a-tape”-Teflon: a new delivery and recovery method for homogeneous fluorous catalysts. Angew. Chem., Int. Ed. 2005, 44, 4095−4097. (16) Studer, A.; Hadida, S.; Ferritto, R.; Kim, S. Y.; Jeger, P.; Wipf, P.; Curran, D. P. Fluorous synthesis: a fluorous-phase strategy for improving separation efficiency in organic synthesis. Science 1997, 275, 823−826. (17) Light Fluorous Chemistry-A User’s Guide. In Handbook of Fluorous Chemistry; Gladysz, J., Horváth, I., Curran, D. P., Eds.; WileyVCH: Weinheim, Germany, 2004; pp 128−155. (18) Curran, D. P. Organic synthesis with light-fluorous reagents, reactants, catalysts, and scavengers. Aldrichimica Acta 2006, 39, 3−9. (19) Matsugi, M.; Suganuma, M.; Yoshida, S.; Hasebe, S.; Kunda, Y.; Hagihara, K.; Oka, S. An alternative and facile purification procedure of amidation and esterification reactions using a medium fluorous Mukaiyama reagent. Tetrahedron Lett. 2008, 49, 6573−6574. (20) Kobayashi, Y.; Inukai, S.; Kondo, N.; Watanabe, T.; Sugiyama, Y.; Hamamoto, H.; Shioiri, T.; Matsugi, M. A medium fluorous Grubbs−Hoveyda 2nd generation catalyst for phase transfer catalysis of ring closing metathesis reactions. Tetrahedron Lett. 2015, 56, 1363− 1366. (21) Vougioukalakis, G. C.; Grubbs, R. H. Ruthenium-based heterocyclic carbene-coordinated olefin metathesis catalysts. Chem. Rev. 2010, 110, 1746−1787. (22) Bieniek, M.; Michrowska, A.; Usanov, D. L.; Grela, K. In an attempt to provide a user’s guide to the galaxy of benzylidene, alkoxybenzylidene, and indenylidene ruthenium olefin metathesis catalysts. Chem. - Eur. J. 2008, 14, 806−818. (23) Clavier, H.; Grela, K.; Kirschning, A.; Mauduit, M.; Nolan, S. P. Sustainable concepts in olefin metathesis. Angew. Chem., Int. Ed. 2007, 46, 6786−6801.

From the bottom HFE layer, the solvent was removed by a rotary vacuum evaporator, affording 1.38 g (34.5%) of the target product fluorous pyridine. 2-Bromo-1-isopropyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoroct-1-enyl)benzene (5). In a glovebox, a flask was charged with 2bromo-4-iodo-1-isopropylbenzene (4, 1.5 g, 4.6 mmol), 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooct-1-ene (4.56 g, 3.00 mL, 13.2. mmol), Pd(OAc)2 (62 mg, 0.28 mmol), Na2CO3 (0.881 g; 8.32 mmol), P(Cy)3 (0.26 g, 0,92 mmol), TBAB (50 mg, 0,16 mmol), and dry DMF (20 mL). The flask was removed from the glovebox and heated to 130 °C for 20 h. After being cooled, the mixture was partitioned between diethyl ether (100 mL) and water (100 mL). The organic phase was separated, and the aqueous layer was extracted with diethyl ether (2 × 100 mL). Combined organic layers were washed with brine (100 mL) and water (100 mL) and dried with anhydrous MgSO4. Solvents were removed on a rotary vacuum evaporator. The crude product was dissolved in 1,2-dichloroethane (10 mL) and extracted with HFE 7500 (3 × 8 mL). Combined HFE layers were partially evaporated to a 5 mL volume and extracted with 1,2dichloroethane (6 × 8 mL). Removal of solvent from the chloroalkane layer gave pure target benzene 5 (1.20 g, 47%, brownish oily liquid). 1-(2-Methoxyethyl)-1-(2,2,4,4,5,5,7,7,8,8,10,10,10-tridecafluoro-3,6,9-trioxadecyl)pyrrolidinum 1,1,2,2,3,3,4,4,4-Nonafluorobutane-sulfonate (8). A flask was charged with alkoxypyrrolidine 10 (0.44 g, 3.4 mmol), fluoroalkyl nonaflate 11 (2.31 g, 3.39 mmol), and toluene (20 mL). The mixture was heated to 108 °C for 7 days. After the mixture was cooled, the solvents were removed on a rotary vacuum evaporator and the crude product was dried in vacuo. The residue was triturated with hexane (4 × 6 mL) while being sonicated (4 × 20 min). The residue was dried in vacuo and dissolved in the mixture of HFE 7500 (2 mL) and 1,2-dichloroethane. The mixture was cooled to −20 °C, and 1,2-dichloroethane was separated; the HFE layer was analogously extracted 5 times by the chlorinated solvent. HFE was finally removed on a vacuum rotary evaporator to give the target ionic liquid 8 (0.72 g, 26%, brownish viscous liquid).

■

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssuschemeng.8b00865. Experimental and analytical details of the synthesis of polyfluoroalkylated dihydroimidazolium salt 9b and 2bromo-4-iodo-1-isopropylbenzene (4); analytical data for all synthesized compounds (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Josef Cvačka: 0000-0002-3590-9009 Jaroslav Kvíčala: 0000-0002-9713-021X Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was supported by specific university research (MSMT No. 21-SVV/2018). Was also thank the 3M company for a kind gift of HFE 7100 and HFE 7500, as well as Prof. O. Mestek for the measurement of the ICP experiments.

■

REFERENCES

(1) Handbook of Fluorous Chemistry; Gladysz, J. A., Curran, D. P., Horváth, I. T., Eds.; Wiley-VCH: Weinberg, 2004. H


Research Article


(43) Kysilka, O.; Rybácǩ ová, M.; Skalický, M.; Kvíčalová, M.; Cvačka, J.; Kvíčala, J. HFPO trimer-based alkyl triflate, a novel building block for fluorous chemistry. Preparation, reactions and 19F gCOSY analysis. Collect. Czech. Chem. Commun. 2008, 73, 1799−1813. (44) Kysilka, O.; Rybácǩ ová, M.; Skalický, M.; Kvíčalová, M.; Cvačka, J.; Kvíčala, J. Fluorous imidazolium room-temperature ionic liquids based on HFPO trimer. J. Fluorine Chem. 2009, 130, 629−639. (45) Macholdt, H.-T.; Elias, H. Inorg. Chem. 1984, 23, 4315−4321. (46) Hensle, E. M.; Tobis, J.; Tiller, J. C.; Bannwarth, W. J. Fluorine Chem. 2008, 129, 968−973. (47) Fang, S.; Zhang, Z.; Jin, Y.; Yang, L.; Hirano, S.-I.; Tachibana, K.; Katayama, S. New functionalized ionic liquids based on pyrrolidinium and piperidinium cations with two ether groups as electrolytes for lithium battery. J. Power Sources 2011, 196, 5637−5644.

(24) da Costa, R. C.; Gladysz, J. A. Syntheses and reactivity of analogues of Grubbs’ second generation metathesis catalyst with fluorous phosphines: a new phase-transfer strategy for catalyst activation. Adv. Synth. Catal. 2007, 349, 243−254. (25) Tuba, R.; Corrêa da Costa, R.; Bazzi, H. S.; Gladysz, J. A. Phase transfer activation of fluorous analogs of Grubbs’ second-generation catalyst: ring-opening metathesis polymerization. ACS Catal. 2012, 2, 155−162. (26) Balogh, J.; Hlil, A. R.; Su, H.-L.; Xi, Z.; Bazzi, H. S.; Gladysz, J. A. An analogue of Grubbs third-generation catalyst with fluorophilic pyridine ligands: fluorous/organic phase-transfer activation of ringclosing alkene metathesis. ChemCatChem 2016, 8, 125−128. (27) Matsugi, M.; Curran, D. P. Synthesis, reaction, and recycle of light fluorous Grubbs-Hoveyda catalysts for alkene metathesis. J. Org. Chem. 2005, 70, 1636−1642. J. Org. Chem. 2005, 70, 1636−1642. (28) Matsugi, M.; Kobayashi, Y.; Suzumura, N.; Tsuchiya, Y.; Shioiri, T. Synthesis and RCM reactions using a recyclable Grubbs-Hoveyda metathesis catalyst activated by a light fluorous tag. J. Org. Chem. 2010, 75, 7905−7908. (29) Kvíčala, J.; Schindler, M.; Kelbichová, V.; Babuněk, M.; Rybácǩ ová, M.; Kvíčalová, M.; Cvačka, J.; Březinová, A. Experimental and Theoretical Study of Hoveyda-Grubbs Catalysts Modified by Perfluorohexyl Ponytail in the Alkoxybenzylidene Ligand. J. Fluorine Chem. 2013, 153, 12−25. (30) Michalek, F.; Bannwarth, W. Application of a Grubbs−Hoveyda metathesis catalyst noncovalently immobilized by fluorous−fluorous interactions. Helv. Chim. Acta 2006, 89, 1030−1037. (31) Mingotaud, A.-F.; Krämer, M.; Mingotaud, C. Catalytic surfactants for ring-opening metathesis polymerization and ringclosing metathesis in non-degassed micellar solutions. J. Mol. Catal. A: Chem. 2007, 263, 39−47. (32) Babuněk, M.; Šimůnek, O.; Hošek, J.; Rybácǩ ová, M.; Cvačka, J.; Březinová, A.; Kvíčala, J. Heavy fluorous phosphine-free ruthenium catalysts for alkene metathesis. J. Fluorine Chem. 2014, 161, 66−75. (33) Skalický, M.; Rybácǩ ová, M.; Kysilka, O.; Kvíčalová, M.; Cvačka, J.; Č ejka, J.; Kvíčala, J. Synthesis of bis(polyfluoroalkylated) imidazolium salts as key intermediates for fluorous NHC ligand. J. Fluorine Chem. 2009, 130, 966−973. (34) Skalický, M.; Skalická, V.; Paterová, J.; Rybácǩ ová, M.; Kvíčalová, M.; Cvačka, J.; Březinová, A.; Kvíčala, J. Ag complexes of NHC ligands bearing polyfluoroalkyl and/or polyfluoropolyalkoxy ponytails. Why Are Polyethers More Fluorous Than Alkyls? Organometallics 2012, 31, 1524−1532. (35) Kolaříková, V.; Šimůnek, O.; Rybácǩ ová, M.; Cvačka, J.; Březinová, A.; Kvíčala, J. Transition Metal Complexes Bearing NHC Ligands Substituted with Secondary Polyfluoroalkyl Groups. Dalton Trans. 2015, 44, 19663−19673. (36) Masoud, S. M.; Mailyan, A. K.; Dorcet, V.; Roisnel, T.; Dixneuf, P. H.; Bruneau, C.; Osipov, S. N. Metathesis catalysts with fluorinated unsymmetrical NHC ligands. Organometallics 2015, 34, 2305−2313. (37) Hošek, J.; Rybácǩ ová, M.; Č ejka, J.; Cvačka, J.; Kvíčala, J. Synthesis of Heavy Fluorous Ruthenium Metathesis Catalysts Using the Stereoselective Addition of Polyfluoroalkyllithium to Sterically Hindered Diimines. Organometallics 2015, 34, 3327−3334. (38) Lipovská, P.; Rathouská, L.; Šimůnek, O.; Hošek, J.; Kolaříková, V.; Rybácǩ ová, M.; Cvačka, J.; Svoboda, M.; Kvíčala, J. Synthesis and catalytic activity of ruthenium complexes modified with chiral racemic per- and polyfluorooxaalkanoates. J. Fluorine Chem. 2016, 191, 14−22. (39) Yu, M. S.; Curran, D. P.; Nagashima, T. Increasing fluorous partition coefficients by solvent tuning. Org. Lett. 2005, 7, 3677−3680. (40) Curran, D. P.; Bajpai, R.; Sanger, E. Purification of fluorous Mitsunobu reactions by liquid-liquid extraction. Adv. Synth. Catal. 2006, 348, 1621−1624. (41) Chu, Q.; Yu, M. S.; Curran, D. P. New fluorous/organic biphasic systems achieved by solvent tuning. Tetrahedron 2007, 63, 9890−9895. (42) Tsai, W.-T. Environmental risk assessment of hydrofluoroethers (HFEs). J. Hazard. Mater. 2005, 119, 69−78. I


Medium Fluorous Separation Using Hydrofluoroether and Weakly

Recommend Documents