JP5300239B2 - Method for oxygenating organic substrates - Google Patents

Description

The present invention relates to a method for oxygenating an organic substrate using a ruthenium complex as a catalyst.

  Catalytic oxidation reactions of organic substrates have been studied using active oxygen such as harsh hydrogen or peracid as an oxygen source. For example, a reaction that oxidizes cyclohexene to adipic acid using a metal oxoacid as a separate catalyst, hydrogen peroxide as an oxidizing agent, and adipic acid in the presence of a phase transfer catalyst has been reported (Non-patent Document 1).

  Thus, it has been studied that metal-oxo complexes become oxidation active species in an aqueous solution using water as an oxygen source instead of hydrogen peroxide and the like to advance the catalytic oxidation reaction of hydrocarbons and alcohols. Specifically, the oxygenation reaction of organic substrates using metal porphyrins was studied (Non-patent Document 2). However, the catalytic oxygenation reaction of organic substrates using high-valent metal oxoporphyrins has so far been limited to oxygenation using active oxygen species (eg, PhIO, hydrogen peroxide, and peracid). These oxygenation reactions require the production of high valent metal oxo species.

Further, a catalytic oxygenation reaction of an organic substrate with manganese porphyrin using water as an oxygen source is also disclosed (Patent Document 1). In the living body, oxygen molecules are reductively activated to oxygenate organic substrates using cytochrome P450 enzymes. This enzymatic reaction activity is known to be a high valent metal porphyrin complex. This high valent metal porphyrin oxo complex is also known to be obtained by reaction of metal porphyrin with active oxygen such as hydrogen peroxide or peracid.
JP-A-2005-255602 (P2005-255602A) Science 1988, 281, 1646 J. et al. Am. Chem. Soc. 1997, 119, 6269-6273

  An object of the present invention is to develop a catalytic oxygenation reaction of an organic substrate using water as an oxygen source.

As a result of intensive studies, the present inventor has produced a ruthenium-oxo complex by an electron transfer reaction using [Ce (NO ₃ ) ₆ ] ^2- ion complex salt, which is a one-electron oxidant, and oxygen of an organic substrate. It was found that the chemical reaction proceeds. It was found that water is an oxygen source and carbonyl compounds are produced with high selectivity.

According to the present invention, Ru is provided the following materials and methods.

( 1 ) In an aqueous solution (however, 5% by weight or less of a water-soluble organic solvent may be contained) , a bisquatris [(2-pyridylmethyl) amine] ruthenium (II) complex salt (however, each The 2-pyridyl groups in the (2-pyridylmethyl) amine ligand may be the same or different and may be substituted with 1 to 3 substituents), and [ Ru (bpy) ₃ ] ³⁺ , (However, bpy is 2,2′-bipyridine which may be substituted, and any pyridyl group in the bipyridine ligand may be the same or different and may be substituted with 1 to 3 substituents. Or oxygenating the organic substrate using [Fe (bpy) ₃ ] ³⁺ (where bpy has the above meaning), and oxygenating the organic substrate .

(2) said organic substrate,
Optionally substituted with 1-3 substituents _C 4 _{-C 10} unsaturated carbocyclic ring,
Benzene optionally substituted with 1 to 3 substituents, or
The method for oxygenating an organic substrate according to ( 1 ), which is a primary alcohol having 2 to 8 carbon atoms.

(3) the organic substrate is
C ₄ -C ₈ cycloalkene, the compound obtained by oxygenation is a dicarboxylic acid,
A benzene derivative substituted with 1 to 3 substituents, wherein the compound obtained by oxygenation is substituted with an aldehyde or a ketone,
A primary alcohol having 3 to 6 carbon atoms and obtained by oxygenation is a carboxylic acid
The method for oxygenating an organic substrate according to (1) or (2) .

(6) Bisquatris [(2-pyridylmethyl) amine] ruthenium (II) complex salt (provided that each of the water-soluble organic solvents may contain 5% by weight or less) The 2-pyridyl groups in the (2-pyridylmethyl) amine ligand may be the same or different and may be substituted with 1 to 3 substituents), and the redox potential (SCE) relative to the saturated calomel electrode. ) Is a one-electron oxidant having a pH of 0.75 to 1.2 V and is stable at a pH of 0 to 2.5, and the organic substrate is oxygenated under the conditions of pH 0 to 2.5. A method for oxygenating an organic substrate, characterized by comprising: The potential (SCE) of (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] is 1.0 V, and the potential of [Ru (bpy) ₃ ] ³⁺ (where bpy is 2,2′-bipyridine). (SCE) is 1.1 V, and the potential (SCE) of [Fe (bpy) ₃ ] ³⁺ (where bpy is 2,2′-bipyridine) is 0.81 V.

  According to the present invention, it is possible to perform catalytic oxygenation of an organic substrate using cheap and safe water instead of active oxygen such as hydrogen peroxide or peracid which has been used as an oxygen source. It was. The present invention is far superior in terms of cost and safety compared to the prior art. Moreover, according to the present invention, various functional groups in an organic compound can be oxygenated with high selectivity.

In a preferred embodiment of the present invention, an organic substrate is oxygenated with a one-electron oxidizing agent in an aqueous solution using a ruthenium complex as a catalyst. The product can be identified by MS and ¹ H-NMR, and the carbonyl compound can be obtained efficiently. In the oxygenation reaction in the method of the present invention, water proceeds as an oxygen source. This was confirmed by MS with heavy water, ie D ₂ O, and the product labeled with D on the product. One-electron oxidizing agents include cerium complexes in which cerium (IV) is the central metal, for example, [Ce (NO ₃ ) ₆ ] ²⁻ , [Ru (bpy) ₃ ] ³⁺ (where bpy is substituted 2,2′-bipyridine, and any pyridyl group in the bipyridine ligand may be the same or different and may be substituted with 1 to 3 substituents) or [Fe (bpy) ₃ ] ³⁺ is used.

  In an embodiment of the present invention, as a ruthenium complex, a bisaquatris [(2-pyridylmethyl) amine ruthenium (II) complex salt (wherein the 2-pyridyl group in each (2-pyridylmethyl) amine ligand is The same or different and may be substituted with 1 to 3 substituents).

FIG. 1 shows the chemical structural formula of this ruthenium complex. In the formula, R is the same or different and is 1 to 3 substituents. These substituents are located in the meta or para position. Substituents are hydrogen atom, halogen atom, hydroxy, cyano, nitro, carboxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-10 alkoxy, —NR ¹ R ² (R ¹ And R ² are the same or different and are a hydrogen atom, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl), —S (O) _m C _1-6 alkyl (where m is Is an integer selected from 0 to 2), C _1-6 alkylcarbonyl, C _2-6 alkenylcarbonyl, C _2-6 alkynylcarbonyl, C _1-6 alkoxycarbonyl. The carbon atom of the hydrocarbon moiety of these substituents may be substituted with one or more halogen atoms or hydroxy.

FIG. 2 shows a method for synthesizing the ruthenium complex. Binuclear complexes are described in Inorg. Chem. 1998, 37, 4076 describes the synthesis method. The binuclear complex reacts with a silver salt dissolved in the solvent in a solvent. The solvent is typically water, but a mixed solvent of water and a water-soluble organic solvent may be used. For example, water is 90% by weight or more, and the water-soluble organic solvent is 10% by weight or less. Examples of the water-soluble silver salt include AgPF ₆ , AgClO ₄ , AgNO _{3 and the} like. This reaction typically proceeds by refluxing. For example, the reaction is performed at 70 to 120 ° C. After the reaction is complete, water-insoluble AgCl precipitates.

FIG. 3 shows a ¹ H-NMR spectrum in the case of the ruthenium complex, in which all Rs are hydrogen atoms.

An organic substrate is oxygenated with a ruthenium complex as a catalyst and a cerium complex in which cerium (IV) as a one-electron oxidant is a central metal, for example, [Ce (NO ₃ ) ₆ ] ²⁻ . In this reaction, the catalytically active species is considered to be the complex shown in FIG. In this catalytically active species, one of the two aqua ligands is converted to an oxo ligand.

Even if it is not a cerium complex, [Ru (bpy) ₃ ] ³⁺ (where bpy is an optionally substituted 2,2′-bipyridine, and any pyridyl group in the bipyridine ligand is The reaction proceeds in the same manner even if they are the same or different and may be substituted with 1 to 3 substituents) or [Fe (bpy) ₃ ] ³⁺ .

The substituent of the pyridyl group is preferably located at the 3-position, 4-position or 5-position. Substituents are hydrogen atom, halogen atom, hydroxy, cyano, nitro, carboxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-10 alkoxy, —NR ¹ R ² (R ¹ And R ² are the same or different and are a hydrogen atom, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl), —S (O) _m C _1-6 alkyl (where m is Is an integer selected from 0 to 2), C _1-6 alkylcarbonyl, C _2-6 alkenylcarbonyl, C _2-6 alkynylcarbonyl, C _1-6 alkoxycarbonyl. The carbon atom of the hydrocarbon moiety of these substituents may be substituted with one or more halogen atoms or hydroxy.

  In one embodiment of the present invention, a bisquatris [(2-pyridylmethyl) amine] ruthenium (II) complex salt (wherein the 2-pyridyl group in each (2-pyridylmethyl) amine ligand) in an aqueous solution. May be the same or different and may be substituted with 1 to 3 substituents.) And an oxygenated organic substrate using a cerium complex wherein cerium (IV) is the central metal.

  The aqueous solution may contain a trace amount of a water-soluble organic solvent, but typically it is preferable that no organic solvent is contained. This is because the one that does not contain an organic solvent is environmentally friendly.

  It is preferable to make it react at 10-120 degreeC, and it is still more preferable to make it react at 10-80 degreeC. The pressure is preferably about 1 atmosphere. However, you may make it react at 0.1-10 atmospheres. The present invention is characterized in that the reaction proceeds even at room temperature.

  For example, 10 μmol to 1 mol of substrate can be used with respect to 1 μmol of bis-aquatris [(2-pyridylmethyl) amine] ruthenium (II) complex salt, that is, ruthenium catalyst. A 0.1 molar substrate can also be used.

  For 1 mmol substrate, 2 to 3 mmol one-electron oxidant can be used, and 2 to 2.5 mmol one-electron oxidant can be used. Also, with respect to the ruthenium catalyst, one to one electron oxidant can be used 4 to 1000 times based on mole, 100 times or more organic substrate can be used, and 1000 times or more organic substrate is used. You can also.

The organic substrate may be a C _{4 to} C ₁₀ unsaturated carbocycle optionally substituted with 1 to 3 substituents, for example, a C _{4 to} C ₈ cycloalkene is oxygenated to form a dicarboxylic acid Is obtained. The substituent is, for example, a C _{1 to} C ₆ hydrocarbon group. The substituent is preferably located at a position other than the alpha position of the double bond. This is because when the substituent is located at the alpha position, the substrate becomes difficult to approach the active center of the catalyst, that is, the ruthenium metal, thereby inhibiting the catalytic reaction.

The organic substrate is benzene optionally substituted with 1 to 3 substituents. For example, a benzene derivative substituted with 1 to 3 substituents is oxygenated and substituted with an aldehyde or a ketone. Benzene derivatives are obtained. In particular, the para position may be substituted with, for example, —SO ₃ M ₁ (M ₁ means an alkali metal such as Na or K).

  The organic substrate is a primary alcohol having 2 to 8 carbon atoms which may be substituted with a phenyl group or a naphthyl group, and a first one having 3 to 6 carbon atoms which may be substituted with a phenyl group or a naphthyl group. The secondary alcohol is oxygenated to give the corresponding carboxylic acid.

Example 1
[RuCl (TPA)] ₂ (PF ₆ ) ₂ (wherein TPA means 2-pyridylmethylamine), that is, chlorotris [(2-pyridylmethyl) amine] ruthenium (II) complex is cojima, etc. Inorg. Chem. It was synthesized by the method described in 1998, 37, 4076.
[RuCl (TPA)] ₂ (PF ₆ ) ₂ was refluxed in an aqueous solution for 6 hours to obtain [Ru (TPA) (OH ₂ ) ₂ ] ₂ (PF ₆ ) ₂ (yield 59%). . The product was identified using ¹ H-NMR, absorption spectrum, and elemental analysis.

Calculated elemental analysis: C, 29.32; H, 2.96; N, 7.72. Found: C, 29.40; H, 3.29; N, 7.62.

Example 2
Example 2-1
3 ml of water or heavy water, cyclohexene (0.5 mmol, 1.7 × 10 ⁻¹ M), (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] (referred to as CAN in this specification as appropriate) ( 1 mmol, 3.3 × 10 ⁻¹ M), [Ru (TPA) (OH ₂ ) ₂ ] (PF ₆ ) ₂ (5 μmol, 1.7 × 10 ⁻³ M) were stirred at room temperature for 1 hour. . Hexanedioic acid, ie adipic acid, was obtained.

Alternatively, water or heavy water, cyclohexene (1.0 × 10 ⁻¹ M), (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] (9.0 × 10 ⁻¹ M), [Ru (TPA) as an organic substrate ) (OH ₂ ) ₂ ] (PF ₆ ) ₂ (1.0 × 10 ⁻³ M) was stirred at room temperature for 1 hour. Adipic acid was obtained.

Example 2-2
Water or heavy water, cyclooctene (1.0 × 10 ⁻¹ M), (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] (9.0 × 10 ⁻¹ M), [Ru (TPA) as organic substrate (OH ₂ ) ₂ ] (PF ₆ ) ₂ (1.0 × 10 ⁻³ M) was stirred at 60 ° C. for 4.5 hours to obtain octanedioic acid.

Example 2-3
Water or heavy water, sodium vinylbenzenesulfonate (1.0 × 10 ⁻¹ M), (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] (8.0 × 10 ⁻¹ M), [Ru as an organic substrate (TPA) (OH ₂ ) ₂ ] (PF ₆ ) ₂ (1.0 × 10 ⁻³ M) was stirred at room temperature for 1 hour. Parasulfonatobenzaldehyde was obtained.

Example 2-4
Water or heavy water, hydroxymethylbenzene (1.0 × 10 ⁻¹ M), (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] (3.0 × 10 ⁻¹ M), [Ru (TPA) as an organic substrate ) (OH ₂ ) ₂ ] (PF ₆ ) ₂ (1.0 × 10 ⁻³ M) was stirred at room temperature for 1 hour. Parasulfonatobenzaldehyde was obtained.

Example 2-5
Water or heavy water, 1-propanol (1.0 × 10 ⁻¹ M), (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] (6.0 × 10 ⁻¹ M), [Ru (TPA) as an organic substrate ) (OH ₂ ) ₂ ] (PF ₆ ) ₂ (1.0 × 10 ⁻³ M) was stirred at room temperature for 1 hour. Propionic acid was obtained.

Example 2-6
As water or heavy water, an organic substrate, parasulfonatoethylbenzene, that is, sodium ethylbenzenesulfonate (1.0 × 10 ⁻¹ M), (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] (6.0 × 10 ⁻¹ M), [Ru (TPA) (OH ₂ ) ₂ ] (PF ₆ ) ₂ (1.0 × 10 ⁻³ M) was stirred at room temperature for 1 hour. Parasulfonatoacetophenone was obtained.

Table 1

Example 3
The durability of the ruthenium catalyst was tested. [Ru (TPA) (OH ₂ ) ₂ ] (PF ₆ ) ₂ (5.0 × 10 ⁻⁴ M), cyclohexene (0.1 M), (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] (1. An aqueous solution of ² × 10 ⁻² M) was stirred at room temperature. After 115 minutes and 165 minutes, (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ] was added in the same amount as the initial stage.

Example 4
Instead of (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ], [Ru (bpy) ₃ ] ³⁺ (where bpy is 2,2′-bipyridine) was used. Sodium vinylbenzenesulfonate was oxygenated to obtain parasulfonatobenzaldehyde (yield 100%).

Example 5
Instead of (NH ₄ ) ₂ [Ce (NO ₃ ) ₆ ], [Fe (bpy) ₃ ] ³⁺ (where bpy is 2,2′-bipyridine) was used. Parasulfonatoethylbenzene, that is, sodium ethylbenzenesulfonate was oxygenated to obtain parasulfonatoacetophenone.

  As described above, the oxygenation reaction of the present invention is a completely new type of oxygenation reaction using water as an electron source, isotope can be easily introduced, and has a very high application value.

  As mentioned above, although this invention has been illustrated using preferable embodiment of this invention, this invention should not be limited and limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range based on the description of the present invention and the common general technical knowledge from the description of specific preferred embodiments of the present invention. Patents, patent applications, and documents cited herein should be incorporated by reference in their entirety, as if the contents themselves were specifically described herein. Understood.

  It is a chemical structural formula of a bisquatris [(2-pyridylmethyl) amine] ruthenium (II) complex salt (R is the same or different and is a substituent).   This is a method for synthesizing a bisquatris [(2-pyridylmethyl) amine] ruthenium (II) complex salt. Are the above ruthenium complex, R are all hydrogen atoms, and shows the ¹ H-NMR spectrum of the _CD 3 in CN when the counterion is PF _6.   It is a chemical structural formula of aquaoxotris [(2-pyridylmethyl) amine] ruthenium (IV) complex (R is the same or different and is a substituent). Examples include oxygenation of an aliphatic C—H bond and ¹ H-NMR spectrum in D ₂ O. Examples are oxygenation of primary alcohols, ¹ H-NMR spectrum in D ₂ O, and the like.   It is a graph about durability of a ruthenium catalyst.   It is a resonance Raman spectrum of aquaoxotris [(2-pyridylmethyl) amine] ruthenium (IV) complex (R is the same or different and is a substituent).   It is a graph which shows the relationship between pH and the oxidation reduction potential (SCE) with respect to a saturated calomel electrode.

Claims (3)

In an aqueous solution (however, 5% by weight or less of a water-soluble organic solvent may be contained)
Bisquatris [(2-pyridylmethyl) amine] ruthenium (II) complex salt (wherein the 2-pyridyl group in each (2-pyridylmethyl) amine ligand is the same or different and has 1 to 3 substitutions) Optionally substituted with a group), and
[ Ru (bpy) 3] ³⁺ , where bpy is an optionally substituted 2,2′-bipyridine, and any pyridyl group in the bipyridine ligand is the same or different and is 1 to 3 Or [Fe (bpy) ₃ ] ³⁺ (where bpy is as defined above),
A method for oxygenating an organic substrate, characterized by oxygenating an organic substrate. The organic substrate is
Optionally substituted with 1-3 substituents _C 4 _{-C 10} unsaturated carbocyclic ring,
Benzene optionally substituted with 1 to 3 substituents, or
The method for oxygenating an organic substrate according to claim 1 , which is a primary alcohol having 2 to 8 carbon atoms which may be substituted with a phenyl group or a naphthyl group. The organic substrate is
C ₄ -C ₈ cycloalkene, the compound obtained by oxygenation is a dicarboxylic acid,
A benzene derivative substituted with 1 to 3 substituents, wherein the compound obtained by oxygenation is substituted with an aldehyde or a ketone,
The organic system according to claim 1 or 2 , wherein the primary alcohol having 3 to 6 carbon atoms which may be substituted with a phenyl group or a naphthyl group, and the compound obtained by oxygenation is a carboxylic acid. Substrate oxygenation method.

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