Salicylate ligands are chelating ligands used in a wide range of organometallic applications and particularly for catalytic applications. In order to decrease the environmental impact of metal-catalyzed reactions, the use of water as solvent has been explored with these ligands by many authors. In this respect, two strategies can be used: the first uses hydrophobic ligands dispersing the catalyst in the aqueous phase (e.g. in ethylene polymerisation , , , or Suzuki-Miyaura couplings , ) and the second uses hydrosoluble salicylate ligands permitting to solubilize the catalyst in the aqueous phase (e.g. in ring-closing metathesis , ethylene polymerization , hydrogenation  or Sonogashira couplings (salen) , ). More recently, sulfonated salicylaldimine and salicylhydrazone ligands have been successfully applied in the rhodium-catalyzed aqueous biphasic hydroformylation of 1-octene (Fig. 1) , , .
In the reported work, TOFs between 200 h−1 and 350 h−1 could be attained with the water-soluble catalysts formed by combining the previous deprotonated ligands (L1–L5, Fig. 1) with the dimeric precursor [RhCl(COD)]2. These N,O-bidentate ligands led to regioselectivities lower than 1.5 except for catalysts containing L1 (where R=−tBu and X=−H) which led to a l/b aldehyde ratio of 2.4 at 50 bar of syngas and 95°C. This behavior is thought to originate from the bulkiness generated close to the metal center favoring the linear aldehyde formation. Linear-to-branched ratios close to this value of 2.4 (2.6 and 2.8, respectively) can be reached using catalyst precursors containing L3 and L2 (where R=−tBu) at lower syngas pressure and temperature (30 bar and 75°C) but the chemoselectivity dropped from 99% to 52% and 56%, respectively.
The sustainability of these processes comes from the fact that the catalyst could be recovered at the end of the reaction after decantation and could subsequently be reused. However, depending on the ligand used, pronounced leaching of the catalyst in the organic phase was observed after several runs.
Parallel to this, cyclodextrins (CDs) have proven to be of particular interest in organometallic chemistry. Indeed, when specifically modified, these macrocycles are able to coordinate a metal precursor to form supramolecular catalysts with exceptional activities and selectivities , , , , , , , . In this context, and with the objective of synthesizing salicylic ligands based on cyclodextrin, we decided to study the condensation of salicylaldehydes with 6A-deoxy-6A-amino-β-CD and 6A-deoxy-6A-hydrazino-β-CD in order to form hydrosoluble Schiff base ligands. The combination of the salicylaldimine skeleton with CDs has already been done with the hope of mimicking enzymes. In these previous cases, the ligands were synthetized starting from hydrophobic salicylaldehydes and were combined with copper(II)  or manganese(III) , ,  in order to study their electrochemical behavior for catalytic oxidation reactions. We focused our attention on sulfonated salicylaldehydes in order to obtain highly hydrophilic ligands able to immobilize rhodium catalyst in the aqueous phase to perform hydroformylation reaction of long chain olefins.
Results and discussion
Synthesis of sulfonatosalicylaldimines and sulfonatosalicylhydrazones
6A-Deoxy-6A-amino-β-cyclodextrin (β-CDNH2) , 6A-deoxy-6A-hydrazino-β-cyclodextrin (β-CDNHNH2)  and the sulfonated salicylaldehyde 1 and 2 (Scheme 1) were prepared according to previously described procedures .
Briefly, the modified β-CDNH2 was readily obtained via a three-step procedure. Native cyclodextrin (β-CD) was first selectively monotosylated (β-OTs) using p-toluenesulfonyl chloride in alkaline solution. Then, the 6A-deoxy-6A-azido-β-cyclodextrin (β-CDN3) was isolated after nucleophilic substitution of β-OTs by sodium azide in DMF solution. Finally, the β-CDN3 was reduced by the Staudinger reaction in the presence of triphenylphosphine to obtain β-CDNH2. In the second step, if hydrazine monohydrate is used as nucleophile, β-CDNHNH2 is obtained.
The sulfonated salicylaldehydes 1 and 2 were prepared by sulfonation of the anilin salicyladimine in sulfuric acid. Then, the sulfonated imines were hydrolysed to give the monosodium salt of the sulfonatosalicylaldehydes (yield=57% for 1 and 67% for 2).
Ligands 3 and 4 were synthesized by a Schiff base condensation in anhydrous N-methylpyrrolidone (NMP) at 80°C for 24 h, followed by a precipitation with acetone (yield 3=80%, yield 4=73%). Ligands 5 and 6 were, for their part, synthesized by Schiff base condensation in DMF at room temperature for 30 min followed by a precipitation with THF (yield 5=67%, yield 6=55%) (Scheme 1).
Characterization of the water-soluble ligands
Both ligands 3 and 4 were characterized by NMR, MALDI-TOF and FT-IR techniques. 13C NMR spectra of the ligands carried out in DMSO-d6 showed a downfield shift of the aldehyde carbon from 191.7 ppm and 198.8 ppm (respectively for 1 and 2) to 167.9 ppm and 168.8 ppm (for 3 and 4), highlighting the formation of the imine functional group. Similarly, in the 1H NMR spectra, signals of the aldehyde protons (10.26 ppm for 1 and 9.78 ppm for 2) disappeared and were replaced by imine protons signals at 8.61 ppm and 8.60 ppm, respectively for 3 and 4. MALDI-TOF spectra obtained in the negative mode validate the previous observations by revealing signals at m/z=1316 and 1372, respectively for 3 and 4, corresponding to the species [M−Na]−. Similar conclusions were obtained from the FT-IR spectra as the imine formation was confirmed by typical C=N absorption bands at 1653 cm−1 and 1651 cm−1, respectively for 3 and 4.
It should be underlined that when the NMR characterizations of ligands 3 and 4 were done in D2O, a remaining signal of the aldehyde was present at 8.44 ppm and 8.47 ppm, respectively. However, in anhydrous DMSO-d6, no aldehyde was observed reflecting a partial stability of the synthesized salicylaldimines in water.
The synthesis of these derivatives is easier than the previous salicylaldimines. Indeed, the coupling between the salicylaldehyde and β-CDNHNH2 could be achieved in water. However, after synthesis optimization, the Schiff base condensation was realized in anhydrous DMF to obtain a higher isolated yield. Again, the synthesized salicylhydrazones were fully characterized (see ESI). Contrary to ligands 3 and 4, NMR characterisation of these new salicylhydrazones could be done in D2O without any significant hydrolysis of the ligand.
In order to check the conformation of the CD in ligands 5 and 6, ROESY experiments were conducted. These experiments could not be carried out with ligands 3 and 4 since these ligands have limited stability in water.
Strong correlations between the aromatic protons of 5 and the CD moiety were highlighted (Fig. 2). Given that these involve the internal protons of the CD (i.e. H3 and H5), it can be deduced that inclusion of the salicylic moiety into the CD cavity took place. The salicylate Ha and Hb protons interact preferentially with the internal H5 and H3 protons of the CD, respectively. In addition, absence of correlations between salicylate Hc and Hd protons with internal H5 protons of the CD suggests an inclusion via the primary face of the CD. Moreover, the substitution of the CD with the salicylate moiety has been done on the primary face of the CD, generating steric hindrance on this side. So, all these observations led us to assume a 360° rotation of the glucopyranose unit bearing the salicylate group leading to a self-inclusion of this moiety (Fig. 2). Such behavior is common for these macrocycles , .
However, the complexation phenomenon with ligand 6 seems to be different. Strong correlation between the tert-Butyl group of the salicylate moiety and the internal CD protons combined with weak interactions between the aromatic protons of the salicylic moiety and the internal CD protons suggests an inter-inclusion with CD cavity occupied by the tert-Butyl group (Fig. 3). Indeed, in the case of a self-inclusion, strong correlations would also appear with the aromatic protons. The strongest correlation was observed between the internal H3 proton of the CD and the tert-Butyl group which suggests an inclusion through the secondary face of the CD (Fig. 3).
Synthesis and characterisation of water-soluble sulfonated Rh(I) complexes
The synthesis of the organometallic rhodium complexes of 3, 4, 5 and 6 was achieved via two different routes: starting from the Schiff base ligands or starting from sulfonated salicylaldehydes (1 and 2) and β-CDNH2 or β-CDNHNH2. In both cases, addition of one equivalent of the Rh precursor [Rh(COD)2+BF4−] to an equimolar aqueous solution of salicylaldehydes (1 or 2) and β-CD (β-CDNH2 or β-CDNHNH2), or Schiff base ligands (3, 4, 5 or 6) leads to the formation of the rhodium complexes. Infrared spectroscopy of these complexes indicates coordination of the Rh center as the ν(C=N) band shifted for example from 1651 cm−1 in ligand 4 to 1600 cm−1 in the rhodium complex 4 (Rh-4). Moreover, the D2O 1H NMR spectra of Rh-4 exhibit an upfield shift of the imine proton from 8.47 ppm to 8.09 ppm (Fig. 4).
Contrary to the metal-free salicylaldimine ligands (3 and 4), the corresponding rhodium complexes (Rh-3 and Rh-4) showed a better water-stability. Indeed, no imine hydrolysis was observed in these cases (Fig. 4 for Rh-4).
The Schiff base rhodium complexes were then evaluated in the aqueous biphasic hydroformylation of 1-decene as a model reaction (Table 1).
The catalyst was firstly formed by mixing the rhodium precursor [Rh(COD)2+BF4−] in water with both one equivalent of ligand 3 and NaOH. Under 50 bar of CO/H2 pressure and at 80°C, an olefin conversion of 81%, a selectivity in aldehydes of 72% and a low linear-to-branched aldehyde ratio of 1.4 was obtained after 6 h (entry 1). Unfortunately, the recovered organic layer was completely black at the end of the reaction suggesting almost complete leaching of the catalyst. To avoid this problem, CO/H2 pressure and temperature were, respectively decreased to 20 bar and 60°C (entry 2). In these conditions, a good conversion of 89% was still observed with an increase of the l/b aldehyde ratio (2.4) but the selectivity dropped to 46% probably due to the syngas pressure decrease favoring 1-decene isomerisation. Moreover, the organic layer was still colored after the catalytic reaction but to a lesser extent compared to entry 1. The use of the complex Rh-4 resulted in a slightly increase of the conversion to 99% but the selectivity was low and the system was still not recyclable (entry 3). 1H NMR experiments conducted on the aqueous phases of entries 1, 2 and 3 showed the presence of the aldehyde proton signal of the sulfosalicylaldehyde demonstrating a partial hydrolysis of the salicylaldimine ligands under the catalytic conditions resulting in catalyst instability. Although Rh-3 and Rh-4 complexes are stable in water at room temperature, these complexes underwent degradation during the catalytic reaction at higher temperatures. The use of the more water stable salicylhydrazone ligands 5 and 6 led to similar results, that is to say total conversion, l/b aldehyde ratio around 2.3 and low chemoselectivities (48% and 40%, respectively) (entries 5 and 7). Furthermore, visual catalyst leaching was confirmed by the coloration of the organic phase. This leaching was also observed at lower conversion suggesting a rapid decomposition of the catalyst (entry 4). The use of five equivalents of the ligand toward the rhodium precursor in order to better immobilize it in the aqueous phase did not lead to a better result (entry 6).
Whatever the experimental conditions, the regioselectivies were rather low (1.4–2.5). These observations are symptomatic of a low coordinated rhodium metal center and consistent with the observed leaching. Concretely, a decoordination of the salicylaldimine ligand under syngas pressure followed by its hydrolysis was supposed. To confirm this hypothesis, experiments have been conducted on the catalytic precursor Rh-5. Heating it up to 80°C in water under inert atmosphere overnight did not lead to any change in the 1H NMR spectrum of the starting complex. However, the same experiment conducted under 1 bar of H2 or syngas rapidly led to a visual decomposition of the catalyst characterized by the formation of black rhodium particles. 1H NMR spectrum of the obtained medium showed the presence of the sulfosalicylaldehyde and the 6A-deoxy-6A-hydrazino-β-CD, demonstrating the thermal decomposition of the starting complex under CO/H2.
New salicylaldimine and salicylhydrazone ligands based on β-CD scaffold were synthesized and fully characterized. Although salicylaldimines underwent hydrolysis at room temperature in water, their rhodium complexes were proved to be stable. The salicylhydrazones are, for their part, more stable given that they did not instantly undergo hydrolysis in water. Interest of these new ligands in the aqueous biphasic hydroformylation reaction is rather limited due to a thermal decomposition of the catalysts under CO/H2 atmosphere leading to a pronounced leaching in the organic layer during the catalytic act. Nevertheless, the use of these ligands in other reactions are currently under investigation in our laboratory.
All reagents and solvents were purchased from Fisher Scientific and Aldrich Chemicals in their highest purity. All chemicals were used as supplied without further purification. Sulfonated salicylaldehydes 1 and 2 were prepared according to literature procedure . β-CD was provided by Roquette Frères. 6A-Deoxy-6A-amino-β-CD and 6A-deoxy-6A-hydrazino-β-CD were synthesized according to slightly modified published procedures , . Carbon monoxide/hydrogen mixture (1:1) was used directly from cylinders (>99.9% pure; air liquide). Distilled water was used in all experiments. NMR spectra were recorded on a Bruker DRX300 spectrometer operating at 300 MHz for 1H nuclei and 75 MHz for JMOD experiments. DMSO-d6 (99.80% isotopic purity) and D2O (99.92% isotopic purity) were purchased from Euriso-Top. Chemical shifts are given in ppm relative to external reference: sodium [D4]-3-(trimethylsilyl)propionate (98% D) in D2O for 1H NMR spectra. Gas chromatography analysis were done on a Shimadzu GC-17A gas chromatograph equipped with a poly-dimethylsiloxane capillary column (30 m×0.32 mm) and a flame ionization detector. Mass spectra were recorded on a MALDI-TOF-TOF Bruker Daltonics Ultraflex II with 2,5-dihydroxybenzoic acid as the matrix.
Synthesis of ligands 3, 4, 5 and 6
Ligands 3 and 4 were synthesized following the same procedure: 0.5 g of 6A-deoxy-6A-amino-β-CD (4.41×10−1 mmol) was dissolved under inert atmosphere in anhydrous NMP (10 mL). One equivalent of the sulfonated salicylaldehyde 1 or 2 was added and the mixture was stirred at 75°C during 24 h. Then the mixture was cooled at room temperature and precipitation with acetone was realized. After filtration and vacuum drying, the Schiff base ligand was obtained as a light yellow solid (yield=79% for 3 and 70% for 4).
1H NMR (DMSO, 298 K): δ 3.35 (overlap with HDO, m, 14H, H-2CD, H-4CD); 3.36–4.10 (m, 28H, H-3CD, H-5CD, H-6CD); 4.48–4.65 (bs, 6H, OH-6CD); 4.83 (m, 7H, H-1CD); 5.72 (m, 14H, OH-2CD, OH-3CD); 6.78 (d, 3J6−5=8.57 Hz, 1H, H6); 7.53 (d, 3J5−6=8.60 Hz, 1H, H5); 7.67 (s, 1H, H3); 8.62 (s, 1H, H1); 13.85 (bs, 1H, OH7). JMOD NMR (DMSO, 298 K): δ 49.1 (C-6ACD); 57.7–60.8 (C-6CD); 70.2 (C-3ACD); 72.5 (C-5CD); 72.9 (C-2CD); 73.5 (C-3CD); 81.5–82.6 (C-4CD); 84.1 (C-4ACD); 102.0–103.0 (C-1CD); 116.6 (C6); 117.3 (C2); 129.5 (C3); 130.7 (C5); 139.0 (C4); 162.8 (C7); 167.9 (C1).
1H NMR (DMSO, 298 K): δ 1.37 (s, 9H, H8); 3.35 (overlap with HDO, m, 14H, H-2CD, H-4CD); 3.48–3.98 (m, 28H, H-3CD, H-5CD, H-6CD); 4.48 (bs, H, OH-6CD); 4.87 (bs, 1H, H-1CD); 5.78 (bs, 14H, OH-2CD, OH-3CD); 7.51 (d, 4J3−5=1.53 Hz, 1H, H3); 7.53 (d, 4J3−5=1.53 Hz, 1H, H5); 8.59 (s, 1H, H1); 14.59 (bs, 1H, OH9). JMOD NMR (DMSO, 298 K): δ 29.5 (C8); 34.9 (C7); 58.1 (C-6ACD); 60.5 (C-6CD); 70.4 (C-3ACD); 72.5 (C-5CD); 72.9 (C-2CD); 73.5 (C-3CD); 82.0 (C-4CD); 84.5 (C-4ACD); 102.4 (C-1CD); 117.1 (C6); 127.4 (C5); 127.9 (C3); 136.3 (C2); 138.0 (C4); 162.3 (C9); 168.9 (C1).
Ligands 5 and 6 were synthesized following the same procedure: 0.1 g of 6A-deoxy-6A-hydrazino-β-CD (87 μmol) was dissolved under inert atmosphere in anhydrous DMF (3 mL). One equivalent of the sulfonated salicylaldehyde 1 or 2 was added and the mixture was stirred at room temperature during 1 h. Then, precipitation with THF was realized. After filtration and vaccum drying, the Schiff base ligand was obtained as a light yellow solid (yield=82% for 3 and 79% for 4).
1H NMR (D2O, 298 K): δ 3.15–3.91 (m, 42H, H-2CD, H-3CD, H-4CD, H-5CD, H-6CD); 4.94–5.03 (m, 7H, H-1CD); 6.75 (d, 3J6−5=8.67 Hz, 1H, H6); 7.47 (dd, 3J5−6=8.67 Hz, 4J5−3=2.02 Hz, 1H, H5); 7.67 (d, 4J3−5=2.02 Hz, 1H, H3); 8.03 (s, 1H, H1). JMOD NMR (D2O, 298 K): δ 58.7 (C-6ACD); 59.4–60.1 (C-6CD); 69.3 (C-3ACD); 71.4–72.1 (C-5CD, C-2CD); 72.9–73.3 (C-3CD); 80.4–81.1 (C-4CD); 83.9 (C-4ACD); 101.9–102.2 (C-1CD); 115.6 (C6); 118.8 (C2); 126.6 (C3); 127.1 (C5); 134.8 (C4); 144.0 (C1); 158.6 (C7).
1H NMR (D2O, 298 K): δ 1.40 (s, 9H, H8); 3.20–3.88 (m, 42H, H-2CD, H-3CD, H-4CD, H-5CD, H-6CD); 5.00 (m, 7H, H1); 7.53 (s, 1H, H3); 7.58 (s, 1H, H5); 8.04 (s, 1H, H1). JMOD NMR (D2O, 298 K): δ 29.2 (C8); 34.6 (C7); 59.8 (C-6ACD); 60.2 (C-6CD); 69.2 (C-3ACD); 71.9–72.0 (C-5CD, C-2CD); 73.1 (C-3CD); 79.9–81.1 (C-4CD); 83.4 (C-4ACD); 101.9–102.5 (C-1CD); 118.4 (C6); 124.2 (C5); 125.6 (C3); 133.3 (C2); 136.7 (C4); 145.1 (C1); 158.1 (C9).
All the high-pressure hydroformylation experiments were carried out in a 25 mL stainless steel autoclave supplied by Parr. All catalytic reactions were performed under nitrogen using standard Schlenk techniques. [Rh(COD)2+BF4−] (41 μmol) and ligand 3, 4, 5 or 6 (1 equiv.) were dissolved in 11.5 mL of degassed water under an inert atmosphere and mixed together overnight. The resulting aqueous phase and an organic phase composed of 1-decene (2.85 g; 500 equiv.) were charged under an inert atmosphere into the 25 mL reactor, which was heated at 60°C or 80°C. Mechanical stirring equipped with a multi-paddle unit was then started (1500 rpm) and the autoclave was pressurized with 20 bar or 50 bar of CO/H2 (1:1) from a gas reservoir connected to the reactor through a high pressure regulator valve keeping the pressure in the reactor constant throughout the whole reaction. The reaction medium was sampled after 6 h of reaction for NMR analyses of the organic phase after decantation.
We thank the Centre National de la Recherche Scientifique (CNRS) for financial support. The authors are grateful to Roquette Frères (Lestrem, France) for generous gifts of β-cyclodextrin. Dominique Prévost is also acknowledged for skillful technical assistance. Campus France and National Research Fondation of South Africa are greatly acknowledged for their financial support (PHC PROTEA N°38229 ZF).
L. C. Matsinha, S. F. Mapolie, G. S. Smith. Dalton Trans. 44, 1240 (2014). Google Scholar
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About the article
Published Online: 2018-03-10
Published in Print: 2018-04-25
Citation Information: Pure and Applied Chemistry, Volume 90, Issue 5, Pages 845–855, ISSN (Online) 1365-3075, ISSN (Print) 0033-4545, DOI: https://doi.org/10.1515/pac-2017-1205.http://creativecommons.org/licenses/by-nc-nd/4.0/.