JP2005075675A - Cationic ruthenium support hydroxyapatite - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a heterogeneous Lewis acid catalyst which is a catalyst holding a high catalytic activity and high reaction selectivity of a noble metal complex catalyst, stable in water, insoluble in a reaction solvent including water, is easily separated, recovered and recycled from a product and is made from hydroxyapatite and a method of manufacturing the same. <P>SOLUTION: This cationic ruthenium support hydroxyapatite is prepared by supporting cationic ruthenium on the hydroxyapatite expressed by the general formula: Ca<SB>10-z</SB>(HPO<SB>4</SB>)<SB>z</SB>(PO<SB>4</SB>)<SB>6-z</SB>(OH)<SB>2-z</SB>-nH<SB>2</SB>O [in the formula, (z) is 0-1 and (n) is 0-2.5]. The catalyst is composed of the cationic ruthenium support hydroxyapatite and its manufacturing method is provided. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a heterogeneous Lewis acid catalyst used in a carbon-carbon bond formation reaction, a cationic ruthenium-supported hydroxyapatite used as the catalyst, and a method for producing the same.

Conventionally, in the field of organic synthesis, particularly fine chemicals, various Lewis acid catalysts have been used for carbon-carbon bond forming reactions (Non-patent Documents 1 and 2). However, conventional Lewis acid catalysts such as AlCl ₃ , TiCl ₄ , and HF-BF ₃ are extremely unstable with respect to water, and further, it is necessary to use benzene or an anhydrous organic solvent containing a halogen atom in the molecule. The handling was inconvenient and there were problems in the environment.

In recent years, as a reaction process that has solved the above problems, it has been desired to develop a Lewis acid catalyst that can be reacted even in an aqueous solution. For this reason, a Lewis acid catalyst system (Patent Document 1 and Patent Document 2) that can be used in an aqueous medium has been recently proposed. However, since these catalysts are water-soluble, separation of the product after the reaction and the catalyst is complicated, and separation and recovery of the catalyst and reuse are difficult.
In addition, Lewis acid catalysts (Non-patent Document 3 and Non-patent Document 4) using a homogeneous noble metal complex have high catalytic activity and high reaction selectivity not found in conventional base metal Lewis acid catalysts. However, since it was difficult to recover expensive catalytic metals and ligands from the reaction mixture after the reaction, the use was actually limited.

In order to solve the problems of these noble metal complexes, efforts are made to fix a complex catalyst system soluble in an organic solvent to an insoluble matrix and easily recover the catalyst metal and ligand from the reaction mixture after the reaction. I came.
However, these hybrid catalysts require a multi-step process in their production, the catalytic activity of the resulting catalyst is inferior to the original homogeneous complex catalyst, or noble metal active components are eluted from the matrix. Etc., the problems of the catalyst have not been solved.

The present inventors have so far found that hydroxyapatite is a potentially excellent macroligand for a noble metal catalytic active center, and have pursued the development of a hybrid catalyst using this. For example, it has been reported that a stable mononuclear ruthenium halide complex supported on hydroxyapatite by an ion exchange method becomes a highly active oxidation catalyst and exhibits excellent reusability (Patent Document 3, Non-Patent Document 5). .
Recently, it has been found that a system obtained by treating such a ruthenium halide complex with silver p-toluenesulfonate serves as a catalyst for the aldol reaction between a nitrile and a carbonyl compound (Non-patent Documents 6 and 7). However, a highly active Lewis acid catalyst that has been widely applied by a carbon-carbon bond formation reaction has not been obtained.

Japanese Patent Laid-Open No. 11-244705 Japanese Patent Laid-Open No. 2000-0240404 JP 2001-246262 A M. Santell, J.-M. Pons, "Lewis Acids and Selectivity in Organic Synthesis", CRS Press, Boca Raton, FL, 1995 "Lewis Acids in Organic Synthesis", H. Yamamoto, Ed., Wiley-VCH, WeinHeim 2000 B. Bosnich, Aldrichimica Act, 1998, 31, 76 S.-I.Murahashi, and H.Takaya, Acc.Chem.Res. 2000,33,225 K. Yamaguchi et al., J. Am. Chem. Soc., 2000, 122, 7144 Chemical Engineering, 2002, 47, 9, 676-682 Chemistry and industry, 2002, 55, 11, pp. 1233-1236

  The present invention is a catalyst that retains the high catalytic activity and high reaction selectivity of the noble metal complex catalyst, is stable to water and insoluble in a reaction solvent containing water, and is separated and recovered from the product. It is an object of the present invention to provide a heterogeneous Lewis acid catalyst that can be easily reused, a hydroxyapatite used as the catalyst, and a method for producing the same.

In order to solve the above problems, the present invention provides a general formula:
Ca _10-Z (HPO ₄ ) _Z (PO ₄ ) _6-Z (OH) _2-Z · nH ₂ O
[Wherein Z is a number from 0 to 1 and n is a number from 0 to 2.5]
A cationic ruthenium-supported hydroxyapatite obtained by supporting cationic ruthenium on a hydroxyapatite represented by the formula:
The present invention also provides a heterogeneous Lewis acid catalyst comprising the cationic ruthenium-supported hydroxyapatite, a method for obtaining a cyclic adduct from an α, β-unsaturated carbonyl compound and a conjugated diene by a Diels-Alder reaction using the catalyst, Provided are a method for obtaining a β-hydroxycarbonyl compound from a silyl enol ether and a carbonyl compound by a Mukaiyama-Aldol reaction using a catalyst, and a method for obtaining an oxazoline derivative from an isonitrile and a carbonyl compound using the catalyst.
Further, (A) a step of treating the hydroxyapatite represented by the above formula with ruthenium trihalide (III) to obtain a ruthenium monohalide-supported hydroxyapatite, and (B) the monohalogen obtained in step (A). There is provided a process for producing the above-mentioned cationic ruthenium-supported hydroxyapatite, which comprises a step of reacting ruthenium fluoride-supported hydroxyapatite with a dehalogenating agent.

The catalyst comprising the cationic ruthenium-supported hydroxyapatite of the present invention is a catalyst that retains the high catalytic activity and high reaction selectivity of the noble metal complex catalyst, is stable to water, and is insoluble in a reaction solvent containing water. As a Lewis acid catalyst that can be easily separated and recovered from the product and reused, the Aldol reaction, Mukaiyama-Aldol reaction, Diels-Alder reaction, allylic substitution reaction, Mannich reaction, Strecker reaction, cycloaddition reaction, Knebenegel It exhibits high catalytic activity for carbon-carbon bond forming reactions such as reactions and parkin reactions.
The production method of the present invention is useful for producing the cationic ruthenium-supported hydroxyapatite.

  The cationic ruthenium-supported hydroxyapatite of the present invention comprises a ruthenium monohalide-supported hydroxyapatite obtained by treating the hydroxyapatite represented by the above general formula with ruthenium trihalide (III), and a dehalogenating agent. It is obtained by reacting.

[Hydroxyapatite]
The hydroxyapatite used as a starting material is, for example, a known method such as an evaporation to dryness method, a solid phase reaction method, a hydrothermal synthesis method, a precipitation reaction method, a hydrolysis method, preferably a hydrothermal synthesis method, a precipitation reaction method, It can be produced by a hydrolysis method, more preferably by a precipitation reaction method.
For example, the following methods are mentioned. First, aqueous ammonia is added to an aqueous solution of ammonium hydrogen phosphate to adjust the pH to 11. To this solution is added a calcium nitrate aqueous solution containing 1.00 to 2.00 molar equivalents, preferably 1.30 to 1.80 molar equivalents, more preferably 1.50 molar equivalents or 1.67 molar equivalents of calcium nitrate, the pH of which has been previously adjusted to 11 with aqueous ammonia. 0-100 ° C, preferably 20-95 ° C, more preferably 70-90 ° C, usually 10-600 minutes, preferably 10-200 minutes, more preferably 10-60 minutes. The hydroxyapatite can be obtained by filtering, washing and drying the resulting precipitate. For example, when 1.50 molar equivalent of calcium nitrate is used, hydroxyapatite with Z = 0 in the above formula: Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ .nH ₂ O, and 1.67 molar equivalent of calcium nitrate are used. , Z = 1 hydroxyapatite: Ca ₉ (HPO ₄ ) (PO ₄ ) ₅ (OH) · nH ₂ O is obtained.
In the above formula, Z must be a number from 0 to 1, preferably 0 to 0.5, and more preferably 0. If Z exceeds 1, a Ca-deficient crystal structure is undesirable. n must be a number from 0 to 2.5, preferably from 0 to 2.0, more preferably from 0 to 1.0. When n exceeds 2.5, the crystal structure changes due to dehydration during handling, which is not preferable.

As the hydroxyapatite is not particularly limited, preferably a BET specific surface area of 10 to 150 m ² / g, more preferably 20 to 100 m ² / g, particularly preferably include those 30~80m ² / g. The crystallite size is not particularly limited, but is preferably 1 to 200 nm, more preferably 5 to 100 nm, and particularly preferably 10 to 80 nm.

[Cationic ruthenium-supported hydroxyapatite]
The cationic ruthenium-supported hydroxyapatite of the present invention is
(A) a step of treating the hydroxyapatite represented by the above formula with ruthenium trihalide (III) to obtain ruthenium monohalide-supported hydroxyapatite;
(B) a step of reacting the ruthenium monohalide-supported hydroxyapatite obtained in the step (A) with a dehalogenating agent,
It can manufacture by the method which has these.

<(A) Process>
Specifically, in the step (A), the ruthenium trihalide (III) (RuX ₃ ) solution is added to the hydroxyapatite slurry represented by the above formula and stirred to convert the ruthenium into the hydroxyapatite. This is a step of obtaining a ruthenium monohalide-supported hydroxyapatite (XRu / HAP) powder supported.

Examples of the ruthenium trihalide (RuX ₃ ) include, for example, ruthenium trichloride (X═Cl), ruthenium tribromide (X═Br), ruthenium triiodide (X═I), and preferably ruthenium trichloride. Can be used. Although the reaction temperature of (A) process is not specifically limited, Usually, 0-100 degreeC, Preferably it is 10-60 degreeC, More preferably, it is 20-40 degreeC. The reaction time is not particularly limited, but is usually 1 to 60 hours, typically 4 to 40 hours, and more typically 6 to 30 hours.
The amount of ruthenium supported on the hydroxyapatite is not particularly limited, but is usually 1.0 μmol / g to 2 mmol / g, preferably 10 μmol / g to 1.5 mmol / g, more preferably 20 μmol / g to 1.2 mmol / g. .

Here, the existence state of XRu / HAP is confirmed by the following method. That is, by performing elemental analysis of XRu / HAP, it was confirmed that one halogen atom remained with respect to one ruthenium atom, and further, a photoelectron spectrum (XPS), an energy dispersive X-ray analyzer (EDX) And X-ray absorption fine structure analysis [including XAFS, broad X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES). The same applies hereinafter. ], The Ru ³⁺ ion is replaced with the Ca ²⁺ ion of hydroxyapatite, and the mononuclear Ru ³⁺ surrounded by four oxygen atoms and one halogen atom is analyzed. It is confirmed that cationic species are generated.

<(B) Process>
Specifically, in the step (B), the ruthenium monohalide-supported hydroxyapatite (XRu / HAP) obtained in the step (A) is used in an amount of 1 to 1.2 times mol, preferably 1.1. This is a step of obtaining a cationic ruthenium-supported hydroxyapatite (Ru ⁺ / HAP) by adding it to an aqueous solution of a double molar dehalogenating agent to make a slurry, and stirring in air or under an inert atmosphere.

Examples of the dehalogenating agent include alkali metals such as lithium, sodium, potassium, rubidium, and cesium, and salts of weakly coordinating anions such as thallium and silver. Preferably, sodium, potassium, or silver is used. Weakly coordinating anion salts, more preferably sodium or silver weakly coordinating anion salts are used. Examples of the weakly coordinating anion salt include tetrafluoroborate (—BF ₄ ), hexafluorophosphate (—PF ₆ ), hexafluoroantimonate (—SbF ₆ ), and p-toluenesulfonic acid. Conventional salts such as a salt, trifluoroacetate, and trifluoromethanesulfonate (-OTf) can be used, preferably hexafluoroantimonate, trifluoromethanesulfonate, and more preferably trifluoromethanesulfonate. Can be used.

When a weakly coordinating anion salt of silver is used as the dehalogenating agent, silver halide insoluble in water is generated as a result of the extraction of the halogen atom. Since the silver halide is obtained in a mixed state with cationic ruthenium-supported hydroxyapatite, it is difficult to separate these silver halides. However, when used as a Lewis acid catalyst, the silver halide is used without being separated. be able to.
When the alkali metal weakly coordinating anion salt is used as the dehalogenating agent, the halogen ion extraction rate is higher than that of thallium or silver weakly coordinating anion salt, particularly silver weakly coordinating anion salt. However, the produced alkali metal halide is soluble in water, and the desired cationic ruthenium-supported hydroxyapatite can be easily isolated by filtration and washing.

Although the reaction temperature of (B) process is not specifically limited, Usually, 0-100 degreeC, Preferably it is 10-80 degreeC, More preferably, it is 20-40 degreeC. The reaction time is the time required for the halogen ion in the ruthenium monohalide-supported hydroxyapatite (XRu / HAP) to be replaced by the dehalogenating agent, and is usually 1 to 40 hours, typically 2 to 2 hours. 20 hours, more typically 4-12 hours.
The atmosphere of the reaction system is not particularly limited, but for example, when handled in air, the resulting cationic ruthenium-supported hydroxyapatite may be partially inactivated as a catalyst, so from the point of maintaining high catalytic activity, It is preferable to handle in an atmosphere of an inert gas such as nitrogen, argon or helium, more preferably nitrogen or argon.

<Characteristics of cationic ruthenium-supported hydroxyapatite>
The structure of the cationic ruthenium-supported hydroxyapatite (Ru ⁺ / HAP) obtained above can be identified by using a combination of elemental analysis, XPS, XANES, and the like. The estimated structure is shown in FIG. Specifically, the identification method is as follows. First, elemental analysis of the cationic ruthenium-supported hydroxyapatite obtained by the treatment of the weakly coordinating anion salt of alkali metal and measurement and data analysis using XPS, halogen ions are added to the cationic ruthenium-supported hydroxyapatite. It is confirmed that it is not included. Then, by performing measurement and data analysis using the K-terminal XANES spectrum of ruthenium of the cationic ruthenium-supported hydroxyapatite, it is confirmed that the spectrum shows a spectrum similar to the original XRu / HAP. From this, it is considered that ruthenium exists in the oxidation state of Ru ³⁺ .
Therefore, it is presumed that ruthenium is supported in a monocation state because ruthenium is in a Ru ³⁺ state and a halogen ion is extracted.

The cationic ruthenium-supported hydroxyapatite of the present invention, when used as a heterogeneous Lewis acid catalyst (hereinafter referred to as “the catalyst of the present invention”), exhibits excellent catalytic activity and reaction selectivity that have not been conventionally obtained.
The features of the cationic ruthenium-supported hydroxyapatite as a heterogeneous Lewis acid catalyst will be described in detail below.

<Features as heterogeneous Lewis acid catalyst>
The cationic ruthenium-supported hydroxyapatite of the present invention is insoluble in a commonly used reaction solvent, particularly an aqueous solvent, and is stable in the reaction solvent. In addition, when the hydroxyapatite is used as a heterogeneous Lewis acid catalyst, it is equivalent to or more than the carbon-carbon bond formation reaction known for the conventional Lewis acid catalyst using a homogeneous complex catalyst. High catalytic activity.

The catalyst of the present invention is, for example, for aldol reaction, mukaiyama-aldol reaction, Diels-Alder reaction, allylic substitution reaction, Mannich reaction, Strecker reaction, cycloaddition reaction, Kunebenegel reaction or Parkin reaction, High catalytic activity for Aldol reaction, Mukaiyama-Aldol reaction, Kunebenegel reaction, or Diels-Alder reaction in non-aqueous solvent.
In particular, when silver hexafluoroantimonate (AgSbF ₆ ) is used as the dehalogenating agent in the step (B) (hereinafter referred to as “Ru ⁺ / HAP- (I)”), the Diels-Alder reaction is high. Shows catalytic activity. When silver trifluoromethanesulfonate (AgOTf) is used as the dehalogenating agent (hereinafter referred to as “Ru ⁺ / HAP- (II)”), aldol reaction, mukaiyama-aldol reaction, cycloaddition reaction It exhibits high catalytic activity for the Knoevenegel reaction and the like.
A typical example of the reaction mode of the reaction using the catalyst of the present invention described above is shown in FIG. In FIG. 1, Scheme 1 is a Diels-Alder reaction mode, Scheme 2 is an Aldol reaction mode, Scheme 3 is an isonitrile cycloaddition reaction mode, and Scheme 4 is a Mukaiyama-Aldol reaction. It is a style. The reaction to which the catalyst of the present invention can be applied is not limited to these representative examples.

  The Diels-Alder reaction, which gives a 1,4-adduct cyclic monoene from a conjugated diene and an olefin, is generally known to proceed remarkably in an aqueous solvent, but extremely slow in an organic solvent ( S. Otto & JBFNEngberts, Pure Appl. Chem., Vol. 72, No. 7, 1365 to 1372 (2000)). On the other hand, the cationic ruthenium-supported hydroxyapatite of the present invention is a heterogeneous Lewis acid catalyst that is extremely effective in promoting the Diels-Alder reaction in an organic solvent.

  Examples of the organic solvent include polar solvents such as ethers, ketones, esters, nitriles, nitrates and halides, toluene, xylene, methanol, ethanol, etc., ethers, ketones, esters, nitriles, nitrates, Polar solvents such as halides are preferred, and nitromethane is particularly preferred. In addition, when the catalyst of the present invention is used, the stereoselectivity of the Diels-Alder reaction is high, and an endo adduct (selectivity: 90 to 100%) can be obtained with high selectivity.

Conventionally known homogeneous Lewis acid catalysts such as [Ru ^III (salen) (NO) H ₂ O] ⁺ SbF ₆ ^- complex and traditional Lewis acid catalysts such as Al, Ti, B, etc. are treated with Diels-Alder reaction. In the case of using an α, β-unsaturated carbonyl compound as an olefin (hereinafter referred to as “dienophile”) as a substrate, the catalytic activity was low.
On the other hand, the Diels-Alder reaction by the catalyst of the present invention, particularly Ru ⁺ / HAP- (I) gives a cycloadduct with an almost quantitative conversion even when an α, β-unsaturated carbonyl compound is used as a dienophile. . In the Diels-Alder reaction using the cationic ruthenium-supported hydroxyapatite catalyst of the present invention, the reaction of the diene and the dienophile of the substrate charged at a molar ratio of 1: 1 is completed, and then the diene and the dienophile at a molar ratio of 1: 1 are again performed. When charged, the reaction further proceeds, and the cycloadduct can be obtained again in the same yield as the first time. Similarly, even if it repeats 3rd time or more, the said reaction can be continued almost without a fall in activity.

Further, when an isonitrile and a carbonyl compound are reacted at room temperature (22 to 28 ° C.) in the presence of the catalyst of the present invention, particularly Ru ⁺ / HAP- (II), an oxazoline derivative is obtained as a product by cycloaddition reaction. Obtained in high yield (80-100%). As a specific example, for example, when isocyanoacetate and benzaldehyde are reacted in the presence of the catalyst, an oxazoline derivative is obtained in a high yield (90 to 100%) and high stereoselectivity (trans: cis = 9: 1). ).
Furthermore, the catalyst of the present invention, particularly Ru ⁺ / HAP- (II), is effective for the aldol reaction between a nitrile and a carbonyl compound in an aqueous solvent, and the corresponding α, β-unsaturated nitrile is obtained in a high yield ( 90-100%).
Aldol addition reaction between dicyanomethane and an alicyclic α, β-unsaturated carbonyl compound is already known (Chemical Engineering, Vol. 47, No. 9, pp. 676 to 682, 2002), but the catalyst of the present invention is used. The aldol reaction is applicable to a wider range of substrates than the above example.

  The compound serving as a donor in the aldol reaction is not particularly limited, and generally a compound having a cyanomethylene group can be widely applied. Preferably, the corresponding α, β-unsaturated nitrile is obtained in a high yield. , Α-cyanomethyl acetate, α-cyanoethyl acetate, α-cyanoacetamide, α-cyanoacetonitrile, and more preferably α-cyanoethyl acetate and α-cyanoacetamide.

  The compound that serves as an acceptor in the aldol reaction is not particularly limited, and in general, various carbonyl compounds such as aliphatic, alicyclic, and aromatic can be widely applied. Preferably, benzaldehyde, cinnamaldehyde, n-butyl are used. Examples include aldehyde, 3-cyclohexene carboxaldehyde, phenyl methyl ketone, phenyl ethyl ketone, cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, cyclononanone, cyclodecanone, cycloundecanone, and cyclododecanone, and more preferably benzaldehyde. Cinnamaldehyde, n-butyraldehyde, 3-cyclohexenecarboxaldehyde, and phenylmethylketone.

  In the reaction in an aqueous solvent, the substrate nitriles, the carbonyl compound and the reaction product α, β-unsaturated nitrile are all insoluble in water, and the catalyst of the present invention is also insoluble in water. In spite of this, sufficiently high catalytic activity and almost quantitative conversion are obtained in suspension by stirring.

In addition, when an α, β-unsaturated carbonyl compound is used as the carbonyl compound in the aldol reaction using the catalyst of the present invention, no 1,4-adduct is formed, and 1,2-addition is selectively performed. Generate only the body. This produces mainly 1,4-adducts when a conventionally known homogeneous complex catalyst such as Ru ^II H ₂ (PPh ₃ ) ₄ is used (S.-I. Murahashi et al., J Am. Chem. Soc., 1995, 117, 12436).

As described above, the catalyst of the present invention, particularly Ru ⁺ / HAP- (II), can also be used in the Mukaiyama-Aldol reaction to give a β-hydroxycarbonyl compound from a silyl enol ether and a carbonyl compound through hydrolysis of a silicon-oxygen bond. Is particularly effective.

The silyl enol ether can be easily synthesized from a carbonyl compound having a C—H bond at the α-position by a dehydrogenation silylation reaction with hydrosilane. The carbonyl compound is not particularly limited, and examples thereof include aliphatic and alicyclic and aromatic ketones and aldehydes, preferably aliphatic, alicyclic and aromatic aldehydes, and more preferably aromatic. Family aldehydes can be used.
In particular, a water-soluble carbonyl compound such as formaldehyde could not be used unless the conventional Lewis acid catalyst such as TiCl ₄ and SnCl ₃ was made anhydrous by complicated operation. Even if water is present, the target product can be obtained in a high yield (80 to 100%) without being affected at all.

Furthermore, since the catalyst of the present invention is extremely stable in an aqueous solvent and no noble metal active component is eluted in the system unlike conventional noble metal complex catalysts, the filtrate after the reaction is inductively coupled plasma (detection sensitivity 0.03 ppm) No ruthenium is detected even when analyzed by the ICP) analysis method. Therefore, the recovered catalyst can be used repeatedly without causing a decrease in catalyst activity.
The catalyst of the present invention is generally used in an amount of 0.01 to 20 mol%, preferably 0.1 to 10 mol%, more preferably 0.5 to 5 mol% with respect to 1 mol of the substrate.

Further, the precursor of the catalyst of the present invention (ClRu / HAP) obtained above, the catalyst of the present invention (Ru ⁺ / HAP- (I) and-(II)), and the intermediate addition of nitrile to the catalyst of the present invention The putative structure of the body (Ru ⁺ / HAP- (II) treated with ethyl cyanoacetate (3a)) was identified using a combination of elemental analysis, XPS, XANES, etc., and the putative structure is shown in FIG. .

EXAMPLES Hereinafter, although this invention is demonstrated using an Example, this invention is not limited to a following example. In the examples and tables, “room temperature” means “22 to 28 ° C.”.
(Synthesis of hydroxyapatite)
<Synthesis example>
40 mmol of diammonium hydrogen phosphate (NH ₄ ) ₂ HPO ₄ was dissolved in 150 mL of water, and a 30% aqueous ammonia solution was added thereto to adjust the pH to 11. Next, while vigorously stirring this solution at 25 ° C., an aqueous solution of 66.7 mmol of calcium nitrate tetrahydrate previously adjusted to a pH of 11 with a 30% aqueous ammonia solution was added dropwise. Stirring was continued after completion of dropping, and the temperature was raised to 90 ° C. over 30 minutes, and the state was maintained for 20 minutes. Thereafter, it was allowed to cool to 25 ° C. over 90 minutes. The obtained crystals are filtered, washed with deionized water until the conductivity of the filtrate becomes 20 μS or less, and then dried by holding at 110 ° C. for 16 hours to obtain the formula: Ca ₁₀ (PO ₄ ) ₆ Hydroxyapatite (HAP-0) represented by (OH) ₂ was obtained.
The hydroxyapatite had a BET specific surface area of 45 m ² / g and a crystallite size of 30 nm as the lattice spacing d = 2.81.

[Production of Cationic Ruthenium-Supported Hydroxyapatite Catalyst]
<Example 1>
To 75 mL of a deionized aqueous solution of 0.0134 M ruthenium chloride hydrate RuCl ₃ .nH ₂ O, 0.9 g of hydroxyapatite (hereinafter referred to as “HAP”) powder was added, and the resulting slurry was stirred at 25 ° C. for 24 hours. . Next, the slurry is filtered, and the solid is washed with deionized water and then dried under vacuum to obtain dark brown ruthenium chloride-supported HAP powder (ClRu / HAP, Ru content: 0.97 mmol / g). It was.
Add 75 mL of deionized water to 1.0 g of this ClRu / HAP powder, stir to make a slurry, add 7.5 mL of deionized aqueous solution containing 0.20 g of sodium trifluoromethanesulfonate (NaOTf), The mixture was kept stirring for 16 hours. Next, by filtration, washing with deionized water, and vacuum drying, 1.1 g of cationic ruthenium-supported HAP catalyst (ie, “Ru ⁺ (OTf) ⁻ / HAP”, hereinafter referred to as “Ru ⁺ / HAP”) Got.

This Ru ⁺ / HAP analysis by powder X-ray fluorescence analysis did not confirm the presence of chlorine above the background. Further, in the photoelectron spectroscopy spectrum of the Ru ⁺ / HAP powder, a peak attributed to Cl ⁻ found in the original ClRu / HAP was not detected. On the other hand, the Ru-K edge XANES spectrum is similar to the original ClRu / HAP, indicating that ruthenium exists in the oxidation state of Ru ³⁺ .
In the EXAFS Fourier transform of the K ³ -weighted ruthenium K-edge, a peak around 3.5 さ れ る attributable to the presence of an adjacent Ru-Ru site was not detected. The inverse Fourier transform of Ru ⁺ / HAP shows that the Ru—Cl bond (2.32Å) in the original ClRu / HAP is a Ru—O bond (2.10Å) attributed to the weakly bound water ligand by treatment with NaOTf. ).
Thus, it is presumed that Ru ⁺ / HAP was formed by forming a cationic ruthenium phosphate complex on the surface of HAP.

[Diels Alder reaction using Ru ⁺ / HAP- (I) catalyst]
<Example 2-1>
In a Pyrex reactor, 0.5 mmol of ClRu / HAP powder as Ru was taken, and 40 mL of water was added while the system was purged with argon, and the mixture was stirred to form a slurry. 4 mL of a deionized aqueous solution of 0.196 g of silver hexafluoroantimonate (AgSbF ₆ ) was added thereto, and stirring was continued at room temperature under an argon stream.
After stirring for 5 hours, the solvent was removed and the solid was dried in vacuo. Next, under an argon atmosphere, 50 mL of nitromethane as a solvent was added, and 10 mmol of cyclopentadiene (1a) as a diene and 12 mmol of methyl vinyl ketone (2a) as a dienophile were added. The resulting mixture was stirred at room temperature, and the progress of the reaction was monitored by gas chromatographic analysis of the reaction solution. Hereinafter, unless otherwise specified, the conversion rate and yield indicate the results of gas chromatographic analysis.
Four hours after the start of the stirring, the substrates (cyclopentadiene and methyl vinyl ketone) disappeared, and 5-acetyl-2-norbornene (endo: exo = 90: 10) was obtained in a yield of 92%. This series of reactions is referred to as “reaction cycle A”. The endo: exo ratio was identified by ¹ H NMR spectrum.

  After completion of the reaction, 10 mmol of cyclopentadiene (1a) and 12 mmol of methyl vinyl ketone (2a) were added to the reaction mixture without isolating the catalyst, and the reaction further proceeded, which was almost the same as the first reaction cycle A. The reaction was complete. Even when the reaction cycle A was repeated three more times, the yield of the cycloadduct did not decrease, and the yield was 92% or more each time.

The same reaction as described above also proceeded with the Ru ⁺ / HAP catalyst isolated in Example 1. On the other hand, such reaction did not proceed when ClRu / HAP, HAP, AgSbF ₆ or AgCl alone or a combination of HAP and AgSbF ₆ or HAP and AgCl before extracting the halogen ions was used.
The obtained results are shown in Table 1.

<Example 2-2>
Example 2 except that 4 mL of deionized aqueous solution of 0.146 g of silver trifluoromethanesulfonate (AgOTf) was added in place of 4 mL of deionized aqueous solution of 0.196 g of silver hexafluoroantimonate (AgSbF ₆ ) as a weakly coordinating anion salt The reaction was carried out in the same manner as -1.
The obtained results are shown in Table 1.

<Example 3>
The reaction was conducted in the same manner as in Example 2-1, except that methyl acrylate (2b) was added instead of methyl vinyl ketone (2a) as a dienophile and the reaction was performed for 5 hours.
The obtained results are shown in Table 1.

<Example 4>
The reaction was conducted in the same manner as in Example 2-1, except that naphthoquinone (2c) was added instead of methyl vinyl ketone (2a) as a dienophile and the reaction was performed for 4 hours.
The obtained results are shown in Table 1.

<Example 5>
Example 2-1 except that cyclohexadiene (1b) instead of cyclopentadiene (1a) as the diene and benzoquinone (2d) instead of methyl vinyl ketone (2a) as the dienophile were added and allowed to react for 6 hours. The reaction was conducted in the same manner.
The obtained results are shown in Table 1.

<Example 6>
Except for adding 2,3-dimethyl-1,3-butadiene (1c) instead of cyclopentadiene (1a) as the diene and benzoquinone (2d) instead of (2a) as the dienophile and reacting for 6 hours, Reaction was performed in the same manner as in Example 2-1.
The obtained results are shown in Table 1.

<Example 7>
Add 2,3-dimethyl-1,3-butadiene (1c) instead of cyclopentadiene (1a) as the diene and maleic anhydride (2e) instead of methyl vinyl ketone (2a) as the dienophile and react for 6 hours A reaction was carried out in the same manner as in Example 2-1, except that the reaction was performed.
The obtained results are shown in Table 1.

[Aldol reaction using Ru ⁺ / HAP- (II) catalyst]
<Example 8-1>
In a Pyrex reactor, 0.05 mmol of ClRu / HAP powder as Ru was taken, and 40 mL of water was added while the system was purged with argon, and the mixture was stirred to form a slurry. To this was added 0.4 mL of a deionized aqueous solution of 14.6 mg of silver trifluoromethanesulfonate (AgOTf), and stirring was continued at room temperature under a stream of argon.
After stirring for 5 hours, the solvent was removed and the solid was dried in vacuo. Next, 5 mL of water was added under an argon atmosphere, and 1 mmol of ethyl cyanoacetate (3a) was further added as a nitrile, and 1.2 mmol of benzaldehyde was added as a carbonyl compound. The resulting mixture was stirred at room temperature, and the progress of the reaction was monitored by gas chromatography analysis of the reaction solution.
After 4 hours from the start of the stirring, the substrates (ethyl acetate and benzaldehyde) disappeared, and (E) -ethyl-2-cyano-3-phenyl-2-propenoate (4a) was obtained in a yield of 99% or more. . The above series of reactions is referred to as “reaction cycle B”. The obtained results are shown in Table 2.

After completion of the first reaction, the obtained reaction mixture was centrifuged to settle the catalyst particles, and the supernatant was removed by decantation. Water and the substrate were added again to the precipitated residual catalyst, and the reaction cycle B was performed under the same conditions as in the first time.
The yield of the second and third (E) -ethyl-2-cyano-3-phenyl-2-propenoate (4a) was 97% in all cases. Thus, the reaction proceeded almost quantitatively each time, and a decrease in the catalyst activity was not confirmed.

<Example 8-2>
Except for adding 0.4 mL of deionized aqueous solution of 19.6 mg of silver hexafluoroantimonate (AgSbF ₆ ) instead of 0.4 mL of deionized aqueous solution of 14.6 mg of silver trifluoromethanesulfonate (AgOTf) as weakly coordinating anion salt Reaction was carried out in the same manner as in Example 8-1.
The obtained results are shown in Table 2.

<Example 9>
The reaction was conducted in the same manner as in Example 8-1 except that cyanoacetamide (3b) was added as a nitrile instead of ethyl cyanoacetate (3a) and reacted for 4 hours.
As a result, the corresponding α, β-unsaturated nitrile product (4b) was obtained. The obtained results are shown in Table 2.

<Example 10>
The reaction was carried out in the same manner as in Example 8-1 except that cinnamaldehyde was added as a carbonyl compound instead of benzaldehyde and the reaction was carried out at 50 ° C. for 8 hours.
As a result, the corresponding α, β-unsaturated nitrile product (4c) was obtained. The obtained results are shown in Table 2.

<Example 11>
The reaction was performed in the same manner as in Example 8-1 except that n-butyraldehyde was added as a carbonyl compound instead of benzaldehyde and the reaction was performed at 50 ° C. for 3 hours.
As a result, the corresponding α, β-unsaturated nitrile product (4d) was obtained. The obtained results are shown in Table 2.

<Example 12>
The reaction was performed in the same manner as in Example 8-1 except that 3-cyclohexenecarboxaldehyde was added as a carbonyl compound instead of benzaldehyde and the reaction was performed at 50 ° C. for 5 hours.
As a result, the corresponding α, β-unsaturated nitrile product (4e) was obtained. The obtained results are shown in Table 2.

<Example 13>
The reaction was performed in the same manner as in Example 8-1 except that dicyanomethane (3c) was added as a nitrile instead of ethyl cyanoacetate (3a) and the reaction was performed at 80 ° C. for 6 hours.
As a result, the corresponding α, β-unsaturated nitrile product (4f) was obtained. The obtained results are shown in Table 2.

<Example 14>
Except that dicyanomethane (3c) was added instead of ethyl cyanoacetate (3a) as a nitrile and cyclohexanone was added as a carbonyl compound instead of benzaldehyde and reacted at 80 ° C. for 3 hours, the same as in Example 8-1. The reaction was performed.
As a result, the corresponding α, β-unsaturated nitrile product (4 g) was obtained. The obtained results are shown in Table 2.

<Example 15>
Example 8-1 except that dicyanomethane (3c) was added as a nitrile instead of ethyl cyanoacetate (3a) and cyclopentanone was added as a carbonyl compound instead of benzaldehyde and reacted at 80 ° C. for 5 hours. The reaction was carried out.
As a result, the corresponding α, β-unsaturated nitrile product (4h) was obtained. The obtained results are shown in Table 2.

<Example 16>
Except that dicyanomethane (3c) was added as a nitrile instead of ethyl cyanoacetate (3a), 2-cyclopentenone (5a) was added as a carbonyl compound instead of benzaldehyde, and the reaction was carried out at 80 ° C. for 8 hours. Reaction was carried out in the same manner as in Example 8-1.
As a result, the corresponding α, β-unsaturated nitrile product was obtained in 90% yield.

<Example 17>
Except that dicyanomethane (3c) was added instead of ethyl cyanoacetate (3a) as a nitrile and 2-cyclohexenone (5b) was added as a carbonyl compound instead of benzaldehyde and reacted at 80 ° C. for 8 hours. The reaction was performed in the same manner as in 8-1.
As a result, the corresponding α, β-unsaturated nitrile product was obtained in 89% yield.

<Example 18>
In a Pyrex reactor, 2 mmol of ClRu / HAP powder as Ru was taken, 4 L of water was added while the inside of the system was purged with argon, and the mixture was stirred to make a slurry. To this was added a 40 mL solution of 0.59 g of silver trifluoromethanesulfonate (AgOTf) in deionized water, and stirring was continued at room temperature under an argon stream.
After stirring for 5 hours, the solvent was removed and the solid was dried in vacuo. Next, 500 mL of water was added under an argon atmosphere, and 100 mmol of ethyl cyanoacetate (3a) was added as a nitrile, and 120 mmol of benzaldehyde was added as a carbonyl compound. The resulting mixture was stirred at 50 ° C. and reacted for 24 hours to obtain 18.9 g (yield: 94%) of the product (E) -ethyl-2-cyano-3-phenyl-2-propenoate (4a). It was.

  When the filtrate after the reaction was analyzed by ICP, Ru was below the detection limit (0.03 ppm). This filtrate was extracted three times with 300 mL of diethyl ether, and the organic layer was concentrated under reduced pressure to obtain 18.1 g (simple) of pure (E) -ethyl-2-cyano-3-phenyl-2-propenoate (4a). (Separation yield: 90%).

[Cycloaddition reaction of carbonyl and isonitrile using Ru ⁺ / HAP- (II) catalyst]
<Example 19>
Except for adding 5 ml of THF instead of water as a solvent and 1 mmol of methyl isocyanoacetate (6) instead of ethyl cyanoacetate (3a) as a nitrile and reacting for 12 hours, the same as in Example 8-1. Reaction was performed. As a result, 4- (methoxycarbonyl) -5-phenyl-2-oxazoline (7) (trans: cis = 9: 1) was obtained in a yield of 90%.
The trans: cis ratio was determined by ¹ HNMR spectrum.

[Mukaiyama-Aldol reaction using Ru ⁺ / HAP- (II) catalyst]
<Example 20>
In a Pyrex reactor, 0.05 mmol of ClRu / HAP powder as Ru was taken, and 40 mL of water was added while the system was purged with argon, and the mixture was stirred to form a slurry. To this was added a solution of 14.6 mg of silver trifluoromethanesulfonate (AgOTf) in 0.4 mL of deionized water, and stirring was continued at room temperature under an argon stream.
After stirring for 5 hours, the solvent was removed and the solid was dried in vacuo. Next, 5 mL of dinitromethane as a solvent was added under an argon atmosphere, and 1 mmol of benzaldehyde and 1.2 mmol of 1-methoxy-1-trimethylsiloxypropene (8a) were further added. The resulting mixture was stirred at room temperature under an argon stream, and the progress of the reaction was monitored by gas chromatographic analysis of the reaction solution.
20 hours after the start of the stirring, 0.1 mL of trifluoroacetic acid and 0.1 mL of deionized water were added. The mixture was further stirred for 30 minutes, and methyl 2-phenyl-2-hydroxy-1-methylpropionate (9a) was obtained as a reaction mixture in a yield of 90%.

<Example 21>
The reaction was conducted in the same manner as in Example 20 except that 1.2 mmol of 1-methoxy-1-trimethylsiloxyethylene (8b) was added instead of 1-methoxy-1-trimethylsiloxypropene. As a result, the corresponding β-hydroxycarbonyl compound (9b) was obtained with a yield of 89%.

<Data analysis>
Ru-K-edge EXAFS analysis and X-ray absorption spectrum measurement of α-cyanoacetate adducts for ruthenium-supported hydroxyapatite, cationic ruthenium-supported hydroxyapatite, and cationic ruthenium-supported hydroxyapatite were performed at the Nishiharima Synchrotron Radiation Research Institute. JASRI Spring-8 beam line 01B1 was attached with a Si (III) monochromator.
Analysis of the data obtained above was performed according to a known method (T. Tanaka et al., J. Chem. Soc., Faraday Trans. 1988, 84, 2987).

FIG. 3 is a graph showing the Fourier transform (FT) of the k ³ -weighted Ru-K-edge EXAFS experimental data of the catalyst precursor of the present invention (ClRu / HAP), and FIG. 3 is a graph showing the inverse Fourier transform (inverse FT). FIG. 4 shows a dotted line (showing a curve fitting suspension in the range of 4 to 12 ^-1 ).
FIG. 5 is a graph showing the Fourier transform (FT) of the k ³ -weighted Ru-K-end EXAFS experimental data of the catalyst of the present invention (Ru ⁺ / HAP- (I)), and FIG. 5 shows the inverse Fourier transform (inverse FT). The graph shown (dotted line indicates curve fitting suspension in the range of 4-12Å- ¹ ) is shown in FIG.
Fourier transform (FT) of k ³ -weighted Ru-K-edge EXAFS experimental data of nitrile addition intermediate to the catalyst of the present invention (Ru ⁺ / HAP- (II) treated with ethyl cyanoacetate (3a)) 7 is a graph showing the inverse Fourier transform (inverse FT), and FIG. 8 is a graph showing the curve fitting suspension in the range of 4 to 12 ^-1 .
In the above, the inverse Fourier transform (inverse FT) was performed in the region of 0.8 to 2.8 cm in FIG. 4, 0.8 to 2.9 cm in FIG. 6, and 0.8 to 2.8 cm in FIG.

  Furthermore, the results of curve fitting analysis are shown in Table 3. Based on the results of FIGS. 3 to 8 and Table 3, (A) ruthenium-supported hydroxyapatite, (B) cationic ruthenium-supported hydroxyapatite, and (C) α-cyanoacetate adducts to cationic ruthenium-supported hydroxyapatite. The structure and the bond distance between atoms were estimated as shown in FIG.

Table 3 Curve fitting analysis of Ru ⁺ / HAP treated with ClRu / HAP, Ru ⁺ / HAP and ethyl cyanoacetate (3a)

^*)Δσ：ＣｌＲｕ／ＨＡＰとそれ以外の試料とのDebye-Waller因子の差異

^*) Δσ: Difference in Debye-Waller factor between ClRu / HAP and other samples

Reaction schemes of typical reactions using the catalyst of the present invention (Scheme 1 is a Diels-Alder reaction scheme, Scheme 2 is an aldol reaction scheme, and Scheme 3 is an isonitrile cycloaddition reaction scheme. And scheme 4 is the reaction mode of the Mukaiyama-Aldol reaction). Catalyst precursors of the invention (ClRu / HAP), catalysts of the invention (Ru ⁺ / HAP- (I) and-(II)) and intermediates of addition of nitriles to the catalysts of the invention (ethyl cyanoacetate (3a ) Is a putative structure of Ru ⁺ / HAP- (II)) treated with FIG. 6 is a graph showing Fourier transform (FT) of k ³ -weighted Ru-K-edge EXAFS experimental data for a precursor of the catalyst of the present invention (ClRu / HAP). Graph showing the inverse Fourier transform (inverse FT) of the k ³ -weighted Ru-K-edge EXAFS experimental data of the precursor of the catalyst of the present invention (ClRu / HAP) (dotted line is a curve in the range of 4 to 12 ^-1 ) Shows fitting suspension). It is a graph which shows the Fourier transform (FT) of the k < ³ > -weighted Ru-K end EXAFS experimental data of the catalyst (Ru ^<+ > / HAP- (I)) of this invention. Graph showing the inverse Fourier transform (inverse FT) of the k ³ -weighted Ru-K-ended EXAFS experimental data of the catalyst of the present invention (Ru ⁺ / HAP- (I)) (the dotted line is in the range of 4 to 12 ^-1 ) Shows a curve fitting suspension). Fourier transform (FT) of k ³ -weighted Ru-K-edge EXAFS experimental data of nitrile addition intermediate to the catalyst of the present invention (Ru ⁺ / HAP- (II) treated with ethyl cyanoacetate (3a)) ). Inverse Fourier transform of k ³ -weighted Ru-K-edge EXAFS experimental data of nitrile addition intermediate (Ru ⁺ / HAP- (II) treated with ethyl cyanoacetate (3a)) to the catalyst of the present invention ( It is a graph (dotted line shows a curve fitting suspension in the range of 4 to 12 ^-1 ) showing an inverse FT).

Claims (8)

General formula:
Ca _10-Z (HPO ₄ ) _Z (PO ₄ ) _6-Z (OH) _2-Z · nH ₂ O
[Wherein Z is a number from 0 to 1 and n is a number from 0 to 2.5]
Cationic ruthenium-supported hydroxyapatite obtained by supporting cationic ruthenium on hydroxyapatite represented by the formula:   The cationic ruthenium-supported hydroxyapatite according to claim 1, wherein the amount of the cationic ruthenium supported on hydroxyapatite is 1.0 µmol / g to 2.0 mmol / g.   A heterogeneous Lewis acid catalyst comprising the cationic ruthenium-supported hydroxyapatite according to claim 1 or 2.   The heterogeneous Lewis acid catalyst according to claim 3 for aldol reaction, mukaiyama-aldol reaction, diels alder reaction, allylic substitution reaction, mannich reaction, strecker reaction, cycloaddition reaction, knoevenegel reaction or parkin reaction.   A process for producing a cycloadduct from a conjugated diene and an α, β-unsaturated carbonyl compound by a Diels-Alder reaction using the catalyst according to claim 3 or 4.   A method for producing a β-hydroxycarbonyl compound from a silyl enol ether and a carbonyl compound by Mukaiyama-Aldol reaction using the catalyst according to claim 3 or 4.   A method for producing an oxazoline derivative from an isonitrile and a carbonyl compound by a cycloaddition reaction using the catalyst according to claim 3. (A) General formula: Ca _10-Z (HPO ₄ ) _Z (PO ₄ ) _6-Z (OH) _2-Z · nH ₂ O
[Wherein Z is a number from 0 to 1 and n is a number from 0 to 2.5]
A step of treating the hydroxyapatite represented by the following formula with ruthenium trihalide (III) to obtain a ruthenium monohalide-supported hydroxyapatite:
(B) a step of reacting the ruthenium monohalide-supported hydroxyapatite obtained in the step (A) with a dehalogenating agent,
The method for producing a cationic ruthenium-supported hydroxyapatite according to claim 1 or 2.

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