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Article

Microwave-Assisted Solvent- and Cu(I)-Free Sonogashira C-C Cross-Coupling Catalysed by Pd Ionanofluids

by
Inês A. S. Matias
,
Ana P. C. Ribeiro
* and
Luísa M. D. R. S. Martins
*
Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
*
Authors to whom correspondence should be addressed.
Processes 2024, 12(7), 1351; https://doi.org/10.3390/pr12071351
Submission received: 4 June 2024 / Revised: 23 June 2024 / Accepted: 26 June 2024 / Published: 28 June 2024
(This article belongs to the Special Issue Advances in Supported Nanoparticle Catalysts (Volume II))
Browse Figures
Versions Notes

Abstract

:
The microwave-assisted Sonogashira C-C cross-coupling reaction catalysed by Pd ionanofluids based on bis(trifluoromethane-sulfonyl)imide (NTf2) ionic liquids, [Cnmim][NTf2] (n = 4, 6 or 8), is described here. An organic solvent- and Cu(I)-free methodology running under very mild conditions was established by creating in situ catalysts from Pd(II) salts and [Cnmim][NTf2]. The microwave-irradiated catalytic systems quickly yielded almost quantitative conversions of 4-bromoanisole and phenylacetylene (model reaction) into the desired 1-methoxy-4-(phenylethynyl)benzene as a single product, and a good recyclability of the Pd ionanofluids.

Graphical Abstract

1. Introduction

The Sonogashira transition-metal-catalysed coupling of terminal alkynes with aryl or vinyl halides/triflates (Scheme 1) is a powerful reaction, being particularly applied in the industrial synthesis of pharmaceuticals [1,2,3,4]. The advantages of this coupling include high yields, functional group compatibility, as well as practical efficiency and simplicity.
Traditional palladium-catalysed Sonogashira C-C cross-couplings occur in organic solvent media (e.g., toluene, THF or DMF) and require the use of a base to eliminate the HX (X = halide) formed during the reaction (Scheme 1) [5]. A copper(I) co-catalyst (requiring an inert atmosphere [6,7]) is also mandatory to accelerate the Sonogashira coupling and avoid the undesirable alkyne C-C homocoupling. However, it brings some difficulties to the catalytic system regarding O2 elimination [5]. Thus, to overcome this problem, copper-free synthetic strategies are highly desired.
In typical catalytic systems, a phosphane, usually Ph3P, as catalyst ligand [7,8,9,10], is crucial to stabilize the Pd(II) soluble species formed via oxidative addition and yield acceptable conversions. Efficient catalytic systems in the absence of phosphane species were also reported, e.g., by Li et al. [11], leading to moderate to high (92%) yields but requiring high loads of the Pd catalyst and nitrogen atmosphere.
Copper-free Sonogashira C-C cross coupling reaction under aerobic and mild conditions were reported by Samangooei et al., where the catalyst, a polystyrene-anchored Pd(II) phenyldithiocarbazate complex, showed good thermal stability and recyclability [12].
Moreover, the increasing awareness of the detrimental health and environmental effects of some organic solvents led to the search for greener technologies [13]. Ionic liquids (ILs), liquid salts usually existing as a liquid below 100 °C or even at room temperature (RTIL), have received a great deal of attention as a possible replacement for volatile organic compounds (VOCs) in catalytic C-C couplings and other important industrial reactions [9,13,14,15,16,17,18,19,20]. Due to their non-measurable vapour pressure and good solubility for other species, as well as the possibility of recycling the catalyst and enhancing the yield and selectivity of the product by using a simple protocol, they have been chosen as reaction media. Moreover, in the case of nanofluids, ILs (due to steric and/or electrostatic effects) can act as stabilizing agents for the monodispersed metal nanoparticles, thus avoiding their agglomeration to bulk metals. ILs may also form a protective layer, preventing nanoparticle surface oxidation [21].
Park et al. [22] developed a copper- and phosphine-free Sonogashira coupling reaction with aryl iodides using the carbenoid species [(bismethylimidazole)PdClMe] in [C4mim][BF4]. However, it required a temperature of 120 °C to be effective, and milder catalytic systems are needed.
In fact, most of the ILs used in Sonogashira and other Pd-catalysed C-C couplings are dialkylimidazolium BF4 or PF6 salts, which can form palladium–NHC, N-heterocyclic carbenes as active catalytic species [22,23,24]. Recently, the authors of [24] mixed NHC-Pd-PPh3 complexes with a methoxyethyl-substituted N-heterocyclic carbene, which were found to catalyse the coupling of aryl bromides to phenylacetylene in the absence of Cu(I), leading to yields up to 99% but required DMF or DMSO and a temperature of 80 °C. Aqueous or alcoholic solvents completely inhibited the coupling reaction [24].
Thus, the design of cheap, easily prepared, and stable palladium catalysts, which allow the Sonogashira cross-coupling to be catalysed with a low Pd loading, under Cu(I)-, solvent- and phosphine-free conditions in atmospheric air, is still a challenge.
In pursuit of our interest in developing strategies to improve the sustainability of catalytic processes [17,25,26,27,28,29,30,31], we have designed new catalytic systems based on in situ-formed Pd ionanofluids from simple and common palladium sources and [NTf2] ILs for use in the copper(I)- and solvent-free Sonogashira C-C coupling of deactivated aryl halide 4-bromoanisole with phenylacetylene under very mild conditions (Scheme 2).
We used microwave (MW) irradiation in the above catalytic transformation, as it was found to be advantageous in previous studies [18,20,26,29,31], leading to more efficient and faster processes. Microwave irradiation produces efficient internal heating by direct coupling of microwave energy with the molecules (solvents, reagents, and catalysts) that are present in the reaction mixture (Figure 1) [32,33]. The temperature increase will, therefore, be uniform throughout the sample since the reaction vessels employed are typically made of microwave-transparent materials such as borosilicate glass, quartz or Teflon. The very efficient internal heat transfer results in minimized wall effects, which may lead to the observation of so-called specific microwave effects, for example, in the context of diminished catalyst deactivation [32].
Dielectric heating effects act by two main mechanisms: dipolar polarization and ionic conduction [33], and in this regard, ionanofluids are particularly suitable to interact with microwaves as they are partly negatively and partly positively charged. In ionic conduction, the charged particles oscillate back and forth under the influence of microwave irradiation. This oscillation causes collisions of the charged particles with neighbouring molecules or atoms, which are ultimately responsible for creating heat energy (Figure 1).
The above expected MW-based improvements were successfully achieved.

2. Materials and Methods

All reagents and solvents were purchased from commercial sources and used as received. The ILs were synthesized according to standard literature procedures [34] and used after drying for 24 h at 70 °C under a high vacuum whilst stirring.
Reactions under microwave (MW) irradiation were performed in a focused Anton Paar Monowave 300 reactor (Anton Paar GmbH, Graz, Austria) fitted with an IR temperature detector and a rotational system in a Pyrex cylindrical tube (10 mL capacity, 13 mm internal diameter).
The 1H and 13C NMR spectra were recorded at ambient temperature using a Bruker Avance II + 300 (Ultra- ShieldTM Magnet) (Bruker, Billerica, MA, USA) spectrometer operating at 300.130 and 75.468 MHz for proton and carbon-13, respectively. The chemical shifts are reported in ppm using tetramethylsilane as an internal reference.
The morphology and distribution of the Pd ionanofluids were characterized using a Hitachi 8100 transmission electron microscope (TEM) with a ThermoNoran light elements EDS detector and digital image acquisition system, and a JEOL 7001F scanning electron microscope (SEM) with Oxford light elements EDS detector and EBSD detector (JEOL, Tokyo, Japan) at Microlab, IST. The Pd ionanofluids were synthesized under MW irradiation. A 10 mL Pyrex tube with a cap was loaded with the palladium precursor (PdCl2, Pd(OAc)2, [PdCl2(PPh3)2] or Pd/C (5% w/w); 0.01 mmol). Then, the ionic liquid [Cnmim][NTf2] (n = 4, 6 or 8) (~1.39 mmol) was added and the mixture placed in the MW reactor and irradiated at 50 °C for 10 or 30 min (15 W, 650 rpm). This resulted in the formation of a black suspension that was analysed by TEM and SEM.

General Procedure for the MW-Assisted Sonogashira C-C Coupling

Sonogashira C-C couplings were carried out under air in 0.5 mL of [Cnmim][NTf2] (n = 4, 6 or 8), contained in a round bottom flask (for the oil bath heating) or in a Pyrex tube (at 15 W and 650 rpm for the MW irradiation), with vigorous stirring.
Typically, 4-bromoanisole (0.2 mmol), phenylacetylene (0.4 mmol), the palladium catalyst precursor [2 mol% of Pd(OAc)2, PdCl2, [PdCl2(PPh3)2] or Pd/C (5% m/m)] and triethylamine (0.5 mmol) were added to the flask/tube, and the reaction performed at 30 or 35–50 °C for the desired time using an oil bath (0.5 to 2 h) or microwave irradiation (10 to 30 min) as the heating mode.
The reaction mixture was then allowed to cool down to room temperature and hexane (5 mL) was added to extract the organic species. The extraction process was repeated four additional times. Then, the residue was dissolved in CDCl3 and analysed by 1H NMR spectroscopy. The yield of the C-C coupling product (relative to 4-bromoanisole) was determined using an internal standard [35].
Blank experiments (replacing the Pd ionanofluid with the corresponding IL) were performed but no C-C coupling product was detected.
Catalyst recyclability under the optimal experimental reaction conditions was investigated. Each cycle was initiated after the preceding one upon the addition of new typical portions of all the other reagents (see above). After the completion of each run, the product phase was separated for analysis (see above) and the Pd ionanofluid was recovered by drying in a vacuum overnight at 70 °C.

3. Results

Pd ionanofluids were successfully formed (Scheme 3) by microwave irradiation of simple and common palladium sources, such as PdCl2, Pd(OAc)2, [PdCl2(PPh3)2] or Pd/C (5% w/w), and 1–alkyl–3–methyl–imidazolium bis(trifluoromethylsulfonyl)imide room temperature ionic liquids [Cnmim][NTf2] (n = 4, 6 or 8; Figure 2).
Imidazolium-based ILs were chosen to serve the dual purposes of a solvent and stabilizer for the preparation of the palladium nanoparticles due to their stability under oxidative and reductive conditions [36], and their ease of synthesis. In our MW-assisted method, the palladium(II) species were rapidly reduced by the different ILs without the aid of any other external reducing agent and at the same time providing the necessary stabilization for the Pd nanoparticles (NPs) in the nanosized pool.
For the Sonogashira reaction promoted by Pd ionanofluids (Scheme 2), the palladium nanoparticles dispersed in the ionic liquid are expected to act as a reservoir of catalytically active Pd species. The nanoparticle size and the degree of dispersion would, most certainly, affect the reservoir potential and consequently the outcome of the catalytic cycle. Thus, the morphology of the prepared Pd ionanofluids was investigated.
Taking advantage from the conductivity of ILs, the morphologic characterization of the ionanofluids by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) was performed without the need for the usual electronic microscopy coating. A small amount of the ionanofluid was placed on a carbon-coated copper grid and directly analysed by TEM (Figure 3a,b) and SEM (Figure 3c,d).
The TEM analysis of the several Pd nanoparticles, formed by the introduction of [Cnmim][NTf2] (n = 4, 6 or 8) ionic liquids, revealed a good dispersion. TEM and SEM micrographs of the ionanofluids formed with PdCl2 or Pd(OAc)2 and [C8mim][NTf2] are presented in Figure 3. The nanoparticles of the ionanofluid that used palladium acetate as the precursor exhibited a spherical shape with a particle size distribution of 5.1 ± 0.39 nm (Figure 3b). The NPs constituting the ionanofluid formed from palladium chloride (Figure 3a) displayed a quasi-spherical shape with a particle size distribution of 14.4 ± 0.76 nm. Small Pd NPs in [C8mim][NTf2] using Pd(OAc)2 were previously obtained by R. Venkatesan et al. [37]; ours are even smaller as they were produced by microwave decomposition instead of by solvothermal method. Pd NPs produced from [PdCl2(PPh3)2] complexes displayed a spherical shape with a particle size distribution of 12.3 ± 0.68 nm. In the case of the NPs obtained from Pd/C, measurement of their size was not possible due to the poor definition of the analysis (see Figure S1, ESI).
SEM images of the Pd ionanofluids displayed the layers of [C8mim][NTf2] and the shape irregularities due to the enveloping layer of ionic liquid (Figure 3c,d).
The copper(I)- and solvent-free Sonogashira C-C coupling of the deactivated aryl halide 4-bromoanisole with phenylacetylene under very mild conditions (Scheme 2) was performed in the presence of triethylamine using microwave irradiation (15 W, 650 rpm) at 35 or 50 °C for a reaction time of 10 min to 30 min (Table 1) or in an oil bath at 30 or 50 °C for 0.5 to 1.5 h (Figure 4). For each catalyst precursor, three ionanofluids were produced in situ with three ILs with different cations (C4 to C8), to evaluate the influence of the side chain length of the IL cation. The results presented in Table 1 and Figure 4 were obtained after optimizing various experimental parameters of the C-C coupling reaction, namely the ratio of aryl halide to phenylacetylene. Under the ionic conditions of this study, a higher excess of phenylacetylene was required (1:2 equiv.) compared to the usual slight excess of the terminal alkyne (1:1.1 equiv. or 1:1.2 equiv.).
The successful copper(I)- and solvent-free Sonogashira C-C coupling of the deactivated aryl halide 4-bromoanisole with phenylacetylene under very mild conditions was significantly dependent on the reaction temperature and time, while selectivity for the desired product (>95%) was always observed (Table 1). The optimized conditions were found to be 30 min of MW irradiation at 50 °C, which allowed us to attain a yield of up to 98% (entry 27, Table 1).
The catalytic activity of the Pd ionanofluids showed a dependence on the IL carbon chain size, with [C8mim] [NTf2] presenting the best results (entries 6–8, 16–18 and 25–17 of Table 1). This can be mainly explained by the increasing viscosity observed from [C4mim] [NTf2] to [C8mim] [NTf2] [38] due to the longer side chains of the imidazolium cations. Regarding the formed Pd nanoparticles, those resulting from the [PdCl2(PPh3)2] precursor were spherical (promoting a more uniform surface in the ionanofluid and better distributed electrostatic interactions), where there is a possibility of having spherical NPs with a larger diameter. In this case, a larger surface area is available to promote the reaction, and improves the stability of the ionanofluid (making it able to withstand the changes associated with MW irradiation) [39]. Thus, the combination of the NPs’ spherical shape/large size with a more viscous IL appears to produce a better catalytic activity for the resulting ionanofluid (entries 19–27, Table 1).
Other aryl halides were tested as substrates, under the above optimized conditions 30 min at 50 °C), for this microwave-assisted Sonogashira C-C coupling catalysed by in situ-prepared Pd ionanofluids from the [PdCl2(PPh3)2] precursor (Table 2). Under the same experimental conditions, the reaction with 4-iodoanisole yielded less product than that with 4-bromoanisole (compare entries 24 and 27 of Table 1 with entries 2 and 3 of Table 2), which can be an indicator of a decreased mobility of the bulky iodide in the presence of viscous ionic liquids, slowing down the reaction.
A comparison of the microwave-irradiation-assisted method with the conventional heating (oil bath) method was performed under the same reaction conditions [Pd precursor (2 mol%), Et3N (0.5 mmol), 4-bromoanisole (0.2 mmol), phenylacetylene (0.4 mmol), [Cnmim][NTf2] (n = 4, 6 or 8; 1.0 µmol)] at 30 and 50 °C. The results obtained in the 0.5 to 2 h range are depicted in Figure 4. Moreover, for the Pd ionanofluid showing the best performance under MW irradiation, [PdCl2(PPh3)2] in [C8mim][NTf2], the reaction was conducted under the same conditions for the same amount of time. The MW-assisted method led to a 93% yield at 50 °C 10 min whereas the oil bath heating yield was only 37%.
Thus, as expected, conductive heating with an external heat source (oil bath) was a comparatively slow and inefficient process for energy transfer into the system (since it depends on convection currents and on the thermal conductivity of the materials that must be penetrated).
As presented in Table 3, our in situ-prepared Pd ionanofluids exhibited, in general, a significantly better performance, leading to higher yields of 1-methoxy-4-(phenylethynyl)benzene at a much lower temperature, and using less time and catalyst than the previously tested catalysts for the copper-free Sonogashira coupling of 4-bromoanisole and phenylacetylene [8,9,10,11,24]. In addition, the present C-C coupling reaction was carried out in air while most of the other systems required an inert atmosphere (N2 or Ar), i.e., these catalytic systems were much more sophisticated and difficult to handle (Table 3).
In fact, Liang and co-workers [8] found that PdCl2, PdCl2/PPh3, [PdCl2(PPh3)2], [Pd(PPh3)4], Pd(dba)2 (dba = bis(dibenzylideneacetone)) and Pd(OAc)2, under dinitrogen, were able to catalyse the Sonogashira C-C coupling of 4-bromoanisole and phenylacetylene in the presence of tetrabutylammonium fluoride (TBAF) without the need for a further solvent. Among the tested catalysts, [PdCl2(PPh3)2] exhibited the best catalytic performance, producing an 86% yield for 1-methoxy-4-(phenylethynyl)benzene after a 3 h reaction (entry 9, Table 3). A relatively low yield was obtained after 3 h when TBAF was replaced with KF (entry 10, Table 3). Using [PdCl2(PPh3)2], Panda et al. [10] found that a Pd–Au dual catalytic system, as well as the presence of DMF under an Ar atmosphere, are required to achieve a 1-methoxy-4-(phenylethynyl)benzene yield (entry 12, Table 3) close to the attained yield in this work (94%). As an alternative, the application of a N-heterocyclic carbene (NHC) was proposed by Touj and co-workers [23], which, interestingly, absolutely requires the presence of t-BuOK (entry 13, Table 3), leading to traces of the C-C coupling product if a triethylamine base is used (entry 14, Table 3).
The catalytic stability of the palladium ionanofluid exhibiting the best performance was investigated in terms of its recyclability. The Pd ionanofluid prepared in situ from [PdCl2(PPh3)2] and [C8mim] [NTf2] used in the C-C coupling of 4-bromoanisole with phenylacetylene (entry 27, Table 1) was reused in three additional consecutive catalytic runs (Figure 5). In each new run, fresh starting materials were added to the previously used catalyst. A decrease in product yield to 75% was observed after the third catalytic cycle, which was drastically reduced in the fourth one (Figure 5). The Pd ionanofluid was recovered from the reaction medium after the fourth run and analysed by TEM. The existence of particle agglomeration explains the reduced activity in this last run. Moreover, insoluble palladium black was detected in the catalytic reaction medium.
From the above, we can say that the present Pd ionanofluids constitute a significant improvement over the state-of-the-art catalytic systems for the Cu(I)-free Sonogashira C-C coupling reaction.

Mechanistic Insights for the Cu-Free Sonogashira Reaction

Although the Cu-free Sonogashira reaction was first reported over four decades ago [40,41], its mechanism is still not fully understood. In the copper-free Sonogashira reaction, the mechanism is similar to the original, where a Cu(I) salt is used as a co-catalyst. The cycle begins with the oxidative addition of the aryl halide to the Pd(0) catalyst, forming a Pd(II) complex with an increased coordination number by two units. This complex undergoes halide replacement in a transmetallation step, followed by reductive elimination. In the absence of copper, a strong base (such as an amine or an alkoxide) deprotonates the terminal alkyne, generating a nucleophilic alkyne anion. This anion then undergoes transmetallation with the Pd(II) complex, forming a palladium(II) acetylide complex. Finally, the Pd(II) acetylide complex undergoes reductive elimination to form the desired coupled product and regenerates the palladium(0) catalyst.
Gazvoda et al. [42] provided experimental evidence and computational support for the completion of the mechanism of the copper-free Sonogashira cross-coupling reaction. According to the authors, the revealed pathway proceeds through a tandem Pd/Pd cycle linked via a multistep transmetallation process. This cycle is virtually identical to the Pd/Cu tandem mechanism of copper-co-catalysed Sonogashira cross-couplings but the role of Cu(I) is played by a set of Pd(II) species.
This copper-free variant avoids the complications associated with copper salts, such as the oxidative homocoupling of alkynes (Glaser coupling) and is particularly useful in synthesizing sensitive or complex molecules where the presence of copper can be detrimental.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/pr12071351/s1, Figure S1: SEM image showing the nanostructure of the Pd/C + [C8mim][NTf2] nanofluid. Figure S2: NMR spectra (300 MHz, 1H, CDCl3) of the extracted product vs. [C4mim][NTf2]. Figure S3: ATR-FTIR spectra of [C4mim] [NTf2]. Figure S4: ATR-FTIR spectra of [C6mim] [NTf2]. Figure S5: ATR-FTIR spectra of [C8mim] [NTf2].

Author Contributions

Conceptualization, L.M.D.R.S.M. and A.P.C.R.; methodology, A.P.C.R. and I.A.S.M.; investigation, I.A.S.M.; writing—original draft preparation, L.M.D.R.S.M. and I.A.S.M.; writing—review and editing, L.M.D.R.S.M.; supervision, L.M.D.R.S.M. and A.P.C.R.; project administration, L.M.D.R.S.M.; funding acquisition, L.M.D.R.S.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by Fundação para a Ciência e Tecnologia (FCT) (projects UIDB/00100/2020 and UIDP/00100/2020) of Centro de Química Estrutural. APCR thanks Instituto Superior Técnico for the Scientific Employment contract IST-ID/119/2018. IASM is thankful to FCT for her PhD fellowship (SFRH/BD/146426/2019).

Data Availability Statement

Data are contained within the article.

Conflicts of Interest

The authors declare no conflicts of interest.

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Processes 12 01351 sch001
Scheme 1. Traditional C-C coupling of alkyl/vinyl halides to terminal acetylenes.
Scheme 1. Traditional C-C coupling of alkyl/vinyl halides to terminal acetylenes.
Processes 12 01351 sch001
Processes 12 01351 sch002
Scheme 2. MW-assisted solvent- and Cu(I)-free Sonogashira C-C cross-coupling of 4-bromoanisole to phenylacetylene.
Scheme 2. MW-assisted solvent- and Cu(I)-free Sonogashira C-C cross-coupling of 4-bromoanisole to phenylacetylene.
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Figure 1. Schematic illustration of the two main dielectric heating mechanisms: dipolar polarization (dipoles align in the microwave field) and ionic conduction (ions move in the microwave field) [33].
Figure 1. Schematic illustration of the two main dielectric heating mechanisms: dipolar polarization (dipoles align in the microwave field) and ionic conduction (ions move in the microwave field) [33].
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Processes 12 01351 g002
Figure 2. Structures of 1-alkyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ionic liquids: (a) 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C4mim][NTf2]; (b) 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C6mim][NTf2]; (c) 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C8mim][NTf2].
Figure 2. Structures of 1-alkyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ionic liquids: (a) 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C4mim][NTf2]; (b) 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C6mim][NTf2]; (c) 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C8mim][NTf2].
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Processes 12 01351 sch003
Scheme 3. Schematic representation of preparation of Pd ionanofluids.
Scheme 3. Schematic representation of preparation of Pd ionanofluids.
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Processes 12 01351 g003aProcesses 12 01351 g003b
Figure 3. TEM (a,b) and SEM (c,d) micrographs showing the in situ-prepared palladium ionanofluids using [C8mim][NTf2]. The metal salts used as precursors were palladium chloride (a,c) and acetate (b,d). Size distribution histograms based in the TEM micrographs are also presented (a,b).
Figure 3. TEM (a,b) and SEM (c,d) micrographs showing the in situ-prepared palladium ionanofluids using [C8mim][NTf2]. The metal salts used as precursors were palladium chloride (a,c) and acetate (b,d). Size distribution histograms based in the TEM micrographs are also presented (a,b).
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Figure 4. Reaction time dependence of the Sonogashira C-C coupling of 4-bromoanisole and phenylacetylene catalysed by in situ-prepared Pd ionanofluids under conventional heating (oil bath) at 50 °C.
Figure 4. Reaction time dependence of the Sonogashira C-C coupling of 4-bromoanisole and phenylacetylene catalysed by in situ-prepared Pd ionanofluids under conventional heating (oil bath) at 50 °C.
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Figure 5. Effect of the catalytic run in the product yield of the MW-assisted Sonogashira C-C coupling between 4-bromoanisole and phenylacetylene in the presence of [PdCl2(PPh3)2] and [C8mim] [NTf2].
Figure 5. Effect of the catalytic run in the product yield of the MW-assisted Sonogashira C-C coupling between 4-bromoanisole and phenylacetylene in the presence of [PdCl2(PPh3)2] and [C8mim] [NTf2].
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Table 1. Microwave-assisted Sonogashira C-C coupling a of 4-bromoanisole and phenylacetylene catalysed by in situ-prepared Pd ionanofluids.
Table 1. Microwave-assisted Sonogashira C-C coupling a of 4-bromoanisole and phenylacetylene catalysed by in situ-prepared Pd ionanofluids.
EntryILPd PrecursorTemperature (°C)Time (min)Yield b (%)Selectivity c (%)TOF d (h−1)
1[C4mim] [NTf2]Pd(OAc)23510859851
25010909954
3[C6mim] [NTf2]3510869953
43530889619
55030939819
6[C8mim] [NTf2]3510869852
75010919756
85030969819
9[C4mim] [NTf2]PdCl23510779946
103530789916
115030859817
12[C6mim] [NTf2]3510789947
133530819816
145010839850
155030879917
16[C8mim] [NTf2]3510819849
17501089>9953
185030929718
19[C4mim] [NTf2][PdCl2(PPh3)2]3510819849
203530909918
215010879852
22[C6mim] [NTf2]3510849750
235010909954
245030949856
25[C8mim] [NTf2]3510889953
265010939956
275030989620
a Pd precursor (2 mol%), Et3N (0.5 mmol), 4-bromoanisole (0.2 mmol), phenylacetylene (0.4 mmol), [Cnmim][NTf2] (n = 4, 6 or 8; 1.0 µmol), 15 W MW power, 650 rpm. b Yield = mol of 1-methoxy-4-(phenylethynyl)benzene/mol of 4-bromoanisole. c Selectivity = mol of 1-methoxy-4-(phenylethynyl)benzene/mol of products. d TOF = (mol of 1-methoxy-4-(phenylethynyl)benzene/mol of Pd)/h.
Table 2. Microwave-assisted Sonogashira C-C coupling a of an aryl halide and phenylacetylene catalysed by in situ prepared Pd ionanofluids ([PdCl2(PPh3)2] used as Pd precursor).
Table 2. Microwave-assisted Sonogashira C-C coupling a of an aryl halide and phenylacetylene catalysed by in situ prepared Pd ionanofluids ([PdCl2(PPh3)2] used as Pd precursor).
EntryILAryl HalideYield b (%)Selectivity c (%)TOF d (h−1)
1[C4mim] [NTf2]4-iodoanisole619824
2[C6mim] [NTf2]669926
3[C8mim] [NTf2]689827
4[C4mim] [NTf2]iodobenzene789931
5[C6mim] [NTf2]799932
6[C8mim] [NTf2]819832
a [PdCl2(PPh3)2] (2 mol%), Et3N (0.5 mmol), aryl halide (0.2 mmol), phenylacetylene (0.4 mmol), [Cnmim][NTf2] (n = 4, 6 or 8; 1.0 µmol), 15 W MW power, 650 rpm. b Yield = mol of 4-(phenylethynyl)benzene/mol of aryl halide. c Selectivity = mol of (phenylethynyl)benzene/mol of products. d TOF = (mol of (phenylethynyl)benzene/mol of Pd)/h.
Table 3. Copper-free Sonogashira C-C coupling of 4-bromoanisole and phenylacetylene catalysed by different palladium catalysts.
Table 3. Copper-free Sonogashira C-C coupling of 4-bromoanisole and phenylacetylene catalysed by different palladium catalysts.
EntryCatalystAmount of Catalyst (mol%)SolventBaseReaction AtmosphereTime (h)Temperature (°C)Yield (%)Ref.
1Pd(OAc)20.5 DMFt-BuOKair180traces[24]
2Pd(OAc)23 TBAF aN2148051[8]
3Pd(OAc)2 + Ph3P4 [C4Py]NO3 bEt3NAr27528[9]
4Pd(OAc)2 + 2-amino pyrimidine-4,6-diol3 + 6MeCNCs2CO3N2216072[11]
5PdCl20.5 DMFt-BuOKair180traces[24]
6PdCl23 -TBAF aN2148025[8]
7PdCl2/PPh33 -TBAF aN238065[8]
8[PdCl2(PPh3)]0.5 DMFt-BuOK 180traces[24]
9[PdCl2(PPh3)2]3 -TBAF aN238086[8]
10[PdCl2(PPh3)2]3 -KFN238016[8]
11[PdCl2(PPh3)2] + [C8mim] [NTf2] c2-Et3Nair0.55098This work
12[PdCl2(PPh3)2] + [AuCl(PPh3)]2 + 2DMFEt3NAr78094[10]
13Processes 12 01351 i0011 DMFt-BuOKair18099[24]
14Processes 12 01351 i0020.5 DMFEt3Nair180traces[24]
15Pd(PPh3)43 -TBAF aN238041[8]
16Pd(dba)2 d3 -TBAF aN2148042[8]
a TBAF = tetrabutylammonium fluoride; b [C4Py] = N-butylpyridinium; c [C8mim] [NTf2] = 1-octyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide; d dba = bis(dibenzylideneacetone).
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Matias, I.A.S.; Ribeiro, A.P.C.; Martins, L.M.D.R.S. Microwave-Assisted Solvent- and Cu(I)-Free Sonogashira C-C Cross-Coupling Catalysed by Pd Ionanofluids. Processes 2024, 12, 1351. https://doi.org/10.3390/pr12071351

AMA Style

Matias IAS, Ribeiro APC, Martins LMDRS. Microwave-Assisted Solvent- and Cu(I)-Free Sonogashira C-C Cross-Coupling Catalysed by Pd Ionanofluids. Processes. 2024; 12(7):1351. https://doi.org/10.3390/pr12071351

Chicago/Turabian Style

Matias, Inês A. S., Ana P. C. Ribeiro, and Luísa M. D. R. S. Martins. 2024. "Microwave-Assisted Solvent- and Cu(I)-Free Sonogashira C-C Cross-Coupling Catalysed by Pd Ionanofluids" Processes 12, no. 7: 1351. https://doi.org/10.3390/pr12071351

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