JP5673124B2 - Palladium catalyst for catalytic reduction - Google Patents

Description

  The present invention relates to a palladium catalyst used in a catalytic reduction reaction.

  The catalytic reduction reaction is a hydrogenation reaction of carbon-carbon multiple bonds. It is the most basic reaction among chemical conversion reactions of organic substances and is used in petroleum catalytic reforming and catalytic cracking processes. Also, it is routinely used in the manufacture of hardened oils such as margarine and shortening.

  In the catalytic reduction reaction, there are many pressurized hydrogenations performed by applying pressure to hydrogen gas. Therefore, the pressure resistance of the device, hydrogen leakage, etc. must be considered. In some cases, heating is required. In the case of a polysubstituted substrate (raw material), activation such as pressurization and heating is particularly necessary. On the other hand, there are many substrates that decompose due to their activation. Many of the catalysts used for the reduction reaction are noble metals, but many of these lose their activity after the reaction and cannot be recycled.

  As a catalyst used for the catalytic reduction reaction, palladium is generally used. Hydrogenation reaction using a palladium catalyst is a very important reaction in organic synthesis. Examples of the catalyst that is routinely used include palladium on carbon (Pd / C). These catalysts are widely used for catalytic hydrogenation of a wide range of reducing functional groups, but have high catalytic activity and are difficult to apply to functional group selective catalytic reduction. In addition, the operability during collection and reuse is not good.

It has been reported that an ionic liquid in which a catalyst is dissolved is taken into the pores of a solid support and catalytic reduction is performed using the ionic liquid (Non-Patent Documents 1 and 2). In Non-Patent Document 1, reduction is performed under pressure using an expensive rhodium complex. That is, the ([Rh (NBD) (PPh ₃ ) ₂ ] PF ₆ complex is immobilized on silica using [bmim] PF ₆ and the catalytic reduction is carried out at room temperature, pressure (600 psi), no solvent or heptane. Recycled 18 times with TOF329 (min ⁻¹ ), and palladium is used in Non-Patent Document 2. That is, Pd nanoparticles are fixed to a molecular sieve using a guanidine ionic liquid, and catalytic reduction is performed at normal pressure. Recycling is carried out 5 times, but all use only very simple olefin compounds as raw materials, and functional group selectivity has not been studied.

  In addition, there is an example in which palladium is immobilized on thiolpropyl group-modified silica gel (no ionic liquid is used) (Non-Patent Documents 3 and 4). In these Non-Patent Documents 3 and 4, palladium is fixed to mesoporous SH-silica and used for Heck reaction and Suzuki coupling reaction. However, none of them are intended for hydrogenation reactions.

C. P. Mehnert, E. J. Mozeleski and R. A. Cook, Chem. Commun., 2002, 3010-3011 J. Huang, T. Jiang, H. Gao, B. Han, Z. Liu, W. Wu, Y. Chang, and G. Zhao, Angew. Chem. Int. Ed. 2004, 43, 1397-1399 C. M. Crudden, M. Sateesh, and R. Lewis, J. Am. Chem. Soc. 2005, 127, 10045-10050 K. Shimizu, S. Koizumi, T. Hatamachi, H. Yoshida, S. Komai, T. Kodama, Y. Kitayama, J. Catalysis 2004, 228, 141-151

  Accordingly, an object of the present invention is to provide a novel catalytic reduction palladium catalyst which can be applied to functional group selective catalytic reduction and has good operability during recovery and reuse.

  As a result of diligent studies to solve the above problems, palladium acetate is supported (immobilized) on silica gel surface-modified with a thiol group, so that it can be applied to various substrates as a catalyst for catalytic reduction and can be recycled. The inventors have found that can be obtained, and have arrived at the present invention.

That is, catalytic reduction for the palladium catalyst according to claim 1 of the present invention, which made by supporting palladium acetate dissolved in silica gel 1-butyl-3-methylimidazolium tetrafluoroborate were surface-modified with thiols groups is there.

Furthermore, the palladium catalyst for catalytic reduction according to claim 2 of the present invention is the catalyst according to claim 1, wherein the silica gel surface-modified with a thiol group is represented by the following formula (wherein R is a methyl group or an ethyl group): It is.

  ADVANTAGE OF THE INVENTION According to this invention, the novel palladium catalyst which can be applied to functional group selective catalytic reduction and has favorable operability at the time of collection | recovery and reuse is provided.

  The palladium catalyst for catalytic reduction of the present invention comprises a palladium compound supported on silica gel surface-modified with a thiol group.

Examples of the palladium compound include palladium acetate (Pd (OAc) ₂ , where (OAc is an acetic acid residue)), palladium salts such as palladium chloride (PdCl ₂ ), palladium black (Pd), tetra (triphenylphosphine) palladium ( Commonly known palladium compounds such as palladium complexes such as Pd (PPh ₃ ) ₄ , where Ph is a phenyl group) are included. Of these, palladium acetate is particularly preferably used.

Here, when palladium acetate is supported on silica gel surface-modified with a thiol group, an ionic liquid may be used. In this case, palladium acetate dissolved in the ionic liquid is supported on silica gel whose surface is modified with a thiol group. The ionic liquid is a liquid at room temperature, preferably 35 ° C. or lower, and can dissolve a palladium compound, and preferably has a high affinity with a thiol group. 1-Butyl-3-methylimidazolium tetrafluoro Borate ([bmim] BF ₄ ), 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] PF ₆ ), 1-hexyl-3-methylimidazolium hexafluorophosphate ([hmim] PF ₆ ), etc. 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim] BF ₄ ) is particularly preferably used.

The thiol group is a substituent in which —SH is bonded to the end of the organic group, and examples of the thiol group for modifying the surface of the silica gel include —CH ₂ SH and — (CH ₂ ) _2. SH, — (CH ₂ ) ₃ SH, — (CH ₂ ) ₄ SH, — (CH 2) ₅ SH and the like can be mentioned. In addition to the above, it may be a thiol group having a side chain. The silica gel whose surface is modified with a thiol group is represented by, for example, the following formula (wherein R is a methyl group or an ethyl group). In addition, the thiol group represented by this formula is called a thiopropyl group. In the following formula, no difference is observed in the catalytic activity of the catalytic reduction palladium catalyst, regardless of whether R is a methyl group or an ethyl group.

  The feature of the palladium catalyst for catalytic reduction of the present invention is that the palladium compound is incorporated into the pores of silica gel whose surface is modified with a thiol group and immobilized using an ionic liquid as necessary. This immobilization operation is extremely simple, and unstable palladium compounds can be stabilized by employing immobilization mediated by an ionic liquid. On the other hand, according to the conventional concept, the thiol group reduces the catalytic activity of the palladium compound. In the present invention, the thiol group contributes to activation and immobilization of the palladium compound.

  The catalytic activity of the catalytic reduction palladium catalyst of the present invention is high, and the reaction can be carried out at normal pressure and room temperature. Since there is no need for a pressurizing device, the device is advantageous. In particular, when a conventional catalyst is used, a polysubstituted olefin that requires pressure conditions can also be reduced at normal pressure and normal temperature. Further, although the catalytic activity of the catalytic reduction palladium catalyst of the present invention is high, it can also be applied to a substrate that has been decomposed when a conventional catalyst is used. Another major feature is that the catalyst can be recycled at least 10 times without reducing its activity by a simple filtration operation.

  Hereinafter, the present invention will be described in detail based on specific examples. In addition, this invention is not restrict | limited by a following example.

  Catalysts were prepared by supporting palladium acetate using an ionic liquid, and various catalytic reduction reactions were attempted.

  [Reaction Example 1]

Immobilization operation:
In a 50 mL two-necked flask, SH-SiO ₂ (powder, 0.300 g), [bmim] BF ₄ (29.9 mg), and Pd (OAc) ₂ (46.6 mg, 0.207 mmol) represented by the following formula were added. And suspended in THF (2 mL).

Thereafter, the mixture was stirred at room temperature for 4 hours under a nitrogen atmosphere, and the solvent was distilled off under reduced pressure. Then, washed with _Et 2 O (× 5), silica gel was dried under reduced pressure to give an orange supported catalyst Pd-SILC (0.373g). The supported amount was 0.51 mmol / g.

Catalyst activation:
Pd-SILC (Pd (OAc) ₂ / SH-SiO ₂ / [bmim] BF ₄ , 0.505 mmol / g, 300 mg) and EtOH (5 mL) were placed in a two-necked flask and stirred at room temperature for 5 hours under a hydrogen atmosphere. The solvent was distilled off under reduced pressure to recover a black supported catalyst. It was stored at room temperature under a nitrogen atmosphere. Even if it was left for more than 3 months, there was no decrease in activity. Moreover, it did not ignite even when placed in the air at room temperature.

  Hereinafter, reduction of various olefins was tried using this supported catalyst.

  [Reaction Example 2]

(E) -3-Methyl-2-cyclopentadecenone (44.6 mg, 0.189 mmol) was placed in a two-necked flask, purged with nitrogen, EtOH (1.9 mL), Pd-SILC (Pd (OAc) _{2 / SH-SiO 2 / [bmim} ] BF 4, 0.472mmol / g) (19.9mg, 0.009mmol) was added, under hydrogen atmosphere and allowed to stir at room temperature and atmospheric pressure for 30 minutes. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After the solvent was concentrated, purification was performed with a short column (EtOAc: hexane = 1: 20). The reduction product (44.7 mg, 0.188 mmol, 99%) was obtained.

  [Reaction Example 3]

(+)-Pregon (46.1 mg, 0.303 mmol) was placed in a two-necked flask, purged with nitrogen, EtOH (3 mL), Pd-SILC (Pd (OAc) ₂ / SH-SiO ₂ / [bmim] BF ₄ , 0.505 mmol / g) (30.2 mg, 0.015 mmol) was added, and the mixture was stirred at room temperature and normal pressure for 30 minutes in a hydrogen atmosphere. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After the solvent was concentrated, purification was performed with a short column (EtOAc: hexane = 1: 6) and MPLC (EtOAc: hexane = 1: 12), and the mixture was concentrated to give a reduced product (40.3 mg, 86%) as 1 1 diastereomer mixture.

  From the above results, it was confirmed that the double bond of the tetrasubstituted α, β-unsaturated ketone can be reduced in a short time.

  It has been confirmed that when Pregon is reduced with Pd / C, phenol is formed as a by-product through dehydrogenation, but this catalyst does not form a by-product.

  The isolation yield of the reduction product is moderate, but this is because the reduction product has a low molecular weight and thus volatilized during the isolation operation.

  [Reaction Example 4]

Cinnamaldehyde (40.0 mg, 0.303 mmol) was placed in a two-necked flask, purged with nitrogen, EtOH (3 mL), Pd-SILC (Pd (OAc) ₂ / SH-SiO ₂ / [bmim] BF ₄ , 0. 505 mmol / g) (30.1 mg, 0.015 mmol) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature and normal pressure for 2 hours. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After the solvent was concentrated, purification was performed by a short column (EtOAc: hexane = 1: 3) and MPLC (EtOAc: hexane = 1: 6). The reduction product (31.7 mg, 78%) was obtained.

  In the reduction of cinnamaldehyde, when Pd / C is used as a catalyst, hydrocinnamyl alcohol or propylbenzene is easily produced as a by-product in parallel with the formation of hydrocinnamaldehyde. It is also known that hydrogenation in EtOH is accompanied by the formation of acetals. However, in this reaction example, such a by-product was not confirmed.

  The isolation yield of the reduction product is moderate, but this is because the reduction product has a low molecular weight and thus volatilized during the isolation operation.

  [Reaction Example 5]

Citral (46.1 mg, 0.303 mmol) was placed in a two-necked flask, purged with nitrogen, EtOH (3 mL), Pd-SILC (Pd (OAc) ₂ / SH-SiO ₂ / [bmim] BF ₄ , 0.472 mmol / G) (32.0 mg, 0.015 mmol) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature and normal pressure for 4 hours. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After the solvent was concentrated, purification was performed by a short column (EtOAc: hexane = 1: 6) and MPLC (EtOAc: hexane = 1: 15). The reduction product (30.5 mg, 64%) was obtained.

  In the reduction of citral, it is known that many by-products are generated including the reduction of formyl group, but the reaction converged to 3,7-dimethyloctanal by carrying out the reaction for a long time.

  The isolation yield of the reduction product is moderate, but this is because the reduction product has a low molecular weight and thus volatilized during the isolation operation.

  [Reaction Example 6]

Cinnamyl alcohol (54.2 mg, 0.404 mmol) was placed in a two-necked flask, purged with nitrogen, EtOH (4 mL), Pd-SILC (Pd (OAc) ₂ / SH-SiO ₂ / [bmim] BF ₄ , 0 .505 mmol / g) (40.2 mg, 0.020 mmol) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature and normal pressure for 2 hours. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After the solvent was concentrated, purification was performed by a short column (EtOAc: hexane = 1: 3) and MPLC (EtOAc: hexane = 1: 6). The reduction product (55.6 mg, quantitative) was obtained.

  The hydroxyl group at the allylic position is susceptible to hydrogenolysis, but only the olefin was reduced in the hydrogenation reaction using cinnamyl alcohol as a substrate.

  [Reaction Example 7]

A raw material (49.2 mg, 0.208 mmol) of the raw material (the left compound of the above formula, Wieland-Miescher ketone derivative) was placed in a two-necked flask, purged with nitrogen, EtOH (2 mL), Pd-SILC (Pd (OAc) ₂ / SH _{-SiO 2 / [bmim] BF 4} , 0.505mmol / g) (20.6mg, 0.010mmol) was added, under hydrogen atmosphere and allowed to stir 4 hours at room temperature, at atmospheric pressure. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After the solvent was concentrated, purification was performed by a short column (EtOAc: hexane = 1: 3) and MPLC (EtOAc: hexane = 1: 3). A reduction product (41.4 mg, 0.174 mol, 84%) was obtained.

  From the above results, it was confirmed that the double bond of the tetrasubstituted α, β-unsaturated ketone can be reduced in a short time.

  [Reaction Example 8]

Isophorone (55.8 mg, 0.404 mmol) was placed in a two-necked flask, purged with nitrogen, EtOH (2 mL), Pd-SILC (Pd (OAc) ₂ / SH-SiO ₂ / [bmim] BF ₄ , 0.505 mmol / G) (40.1 mg, 0.020 mmol) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature and normal pressure for 40 minutes. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After concentrating the solvent, purification was performed with a short column (EtOAc: hexane = 1: 6), and concentration was performed to obtain a reduced product (57.4 mg, quantitative).

  [Reaction Example 9]

A raw material (the left compound of the above formula, Bn is a benzyl group) (54.9 mg, 0.206 mmol) (54.9 mg, 0.206 mmol) was placed in a two-necked flask, and the atmosphere was purged with nitrogen. EtOH (2.1 mL), Pd-SILC (Pd (OAc) _{2 / SH-SiO 2 / [bmim} ] BF 4, 0.516mmol / g) (20.0mg, 0.0103mmol) was added, under hydrogen atmosphere and allowed to stir at room temperature and atmospheric pressure for 30 minutes. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After the solvent was concentrated, purification was performed with a short column (EtOAc: hexane = 9: 1) to obtain a reduced form (52.2 mg, 0.193 mmol, 94%).

  Under normal catalytic reduction conditions, the benzyloxy group was deprotected but was stable under these conditions.

[Reaction Examples 10 to 16]
The reaction examples 10 to 16 carried out in the same manner as described above are summarized in the table.

  The acetoxy group that was deprotected under basic conditions (reaction example 10) and the t-butyldimethylsiloxy group that was deprotected under acidic conditions (reaction example 11) were stable. The benzyloxy group deprotected under catalytic reduction conditions was stable even under 24 hours of hydrogen contact (Reaction Example 12). Reduction of cholesterol gave a single stereoisomer (Reaction Example 13). The nitro group was not reduced, and only the double bond was reduced (Reaction Example 16).

[Reaction Example 17]
Recycling experiment:
In a two-necked flask, cyclohexene (256 μL, 0.207 g, 2.525 mmol), toluene (27 μL, 23.3 mg, 0.2525 mmol) as internal standards, EtOH (2.5 mL), Pd− previously reduced and stored SILC (Pd (OAc) ₂ / SH-SiO ₂ / [bmim] BF ₄ , 0.505 mmol / g) (25.0 mg, 0.0126 mmol) was added, and the mixture was stirred at room temperature and normal pressure for 70 minutes in a hydrogen atmosphere. It was. The reaction solution was qualitatively and quantitatively analyzed by gas chromatography. The conversion rate was 100% (target product: cyclohexane (2.528 mmol)). After the reaction, decantation was performed with Et ₂ O, and the catalyst was dried under reduced pressure.

  This catalyst was used in the next experiment. The results are shown in the table.

  As described above, the present catalyst was easily recovered by filtration. Pd / C also shows the same reactivity, but far superior in operability during recovery and reuse. Further, the catalyst could be reused at least 10 times without reducing the activity after recovery. The catalyst rotation number (TON) for cyclohexene reduction reached 40,000. If the efficiency of gas-liquid contact is improved, it is thought that it will increase further.

[Reference Example 1]
When palladium acetate was supported on the ionic liquid using [bmim] PF ₆ , an orange powder was obtained. This was immediately used as a catalytic hydrogenation catalyst, but the reaction rate was slow in the reduction of cyclohexene.

[Reference Example 2]
The ionic liquid using [bmim] NTf ₂ was attempted loading of palladium acetate but, [bmim] NTf ₂ is not fixed.

[Reference Example 3]
When palladium acetate was supported on aminopropyl group-modified silica gel using [bmim] PF ₆ , an orange powder was obtained. On the other hand, the immobilized catalyst in which palladium acetate was supported on N, N-diethylaminopropyl group-modified silica gel using [bmim] PF ₆ had already been reduced to palladium black during the supporting operation. These were immediately used as catalytic hydrogenation catalysts, but the reaction rate was slow in the reduction of cyclohexene.

[Reference Example 4]
When palladium acetate was supported on normal phase silica gel using [bmim] PF ₆ , a light yellow powder was obtained. This was immediately used as a catalytic hydrogenation catalyst, but the reaction rate was slow in the reduction of cyclohexene.

  Catalysts were prepared by supporting palladium acetate without using an ionic liquid, and various catalytic reduction reactions were attempted.

[Reaction Example 18]
Immobilization operation:
SH-SiO ₂ in a two-neck flask 50 mL _(powder, 0.525 g), placed Pd (OAc) 2 (67.4mg, 0.30mmol), was suspended in THF (3 mL). Thereafter, the mixture was stirred at room temperature for 4 hours under a nitrogen atmosphere, and the solvent was distilled off under reduced pressure. Then, washed with _Et 2 O (× 5), it was dried over silica gel under reduced pressure to give an orange supported catalyst (0.635 g). The supported amount was 0.472 mmol / g.

Catalyst activation:
The above supported catalyst and EtOH (5 mL) were placed in a two-necked flask and stirred at room temperature for 5 hours under a hydrogen atmosphere, and the solvent was distilled off under reduced pressure to recover a black supported catalyst. It was stored at room temperature under a nitrogen atmosphere.

  Hereinafter, reduction of various olefins was tried using this supported catalyst.

[Reaction Example 19]
Cinnamaldehyde (41.8 mg, 0.315 mmol) was placed in a two-necked flask, purged with nitrogen, EtOH (3.2 mL), Pd-SILC (Pd (OAc) ₂ / SH-SiO ₂ , 0.525 mmol / g) (30.1 mg, 0.0158 mmol) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature and normal pressure for 75 minutes. The reaction solution was separated using a centrifuge, and the catalyst was washed with Et ₂ O (× 5). After the solvent was concentrated, purification was performed by a short column (EtOAc: hexane = 1: 3) and MPLC (EtOAc: hexane = 1: 6). A reduction product (26.3 mg, 62%), its diethyl acetal compound (4.5 mg, 7.4%), and cinnamaldehyde (2.2 mg, 5.3%) were obtained.

[Reaction Example 20]
Recycling experiment:
The reaction rate of the catalytic hydrogenation of cyclohexene was fast and could be recycled 10 times. However, it took some time to complete the reaction as compared with Reaction Example 9.

Claims (2)

A palladium catalyst for catalytic reduction obtained by supporting palladium acetate dissolved in 1-butyl-3-methylimidazolium tetrafluoroborate on silica gel surface-modified with a thiol group. Surface modified silica gel is represented by the following formula with a thiol group (wherein, R is a methyl group or an ethyl group) catalytic reduction for the palladium catalyst according to claim 1, which is represented by.