JP6218140B2 - Magnetic iron particle supported iodine catalyst - Google Patents

Description

The present invention relates to an iodine catalyst used for an oxidation reaction of alcohols or phenols and a method for producing a corresponding oxo compound from alcohols or phenols using the same.

Aldehydes, ketones, carboxylic acids and their derivatives are the main constituent substituents of the chemical structures of many organic natural products and pharmaceuticals, and are constructed by oxidation reactions of primary alcohols or secondary alcohols. Therefore, these oxidation reactions are the most important reactions in the production of organic compounds. Also, in organic synthetic chemistry, these oxidation reactions are one of basic reactions, and many excellent oxidizing agents and oxidation methods have been developed.
Classically, heavy metal oxidants such as chromium (VI) compounds have been used, but transition metals such as ruthenium, manganese and vanadium, and further activated dimethyl sulfoxide have been developed.
However, the use of metal compounds has problems such as adverse effects on the environment and the inclusion of trace metals in products, and the use of dimethyl sulfoxide is a foul odor after completion of the reaction, which requires improvements in environmental harmony and safety. Yes. In particular, these are the most important issues from the industrial viewpoint of pharmaceuticals, cosmetics, agricultural chemicals, foods, and the like.

In recent years, hypervalent organic iodine compounds having pentavalence exceeding the normal valence are widely used as oxidants for alcohols instead of conventional heavy metal oxidants.
For example, 2-iodobenzoic acid and its derivatives, 4-alkoxyiodobenzene and its derivatives are used as iodine catalysts. When these catalysts are reacted with oxone (hydrogen persulfate ion, double salt composed of sulfate ion and hydrogen sulfate ion) or peracid in the presence of alcohols or phenols, the corresponding oxidation products can be obtained in high yield. (Non-Patent Document 1).

Tetrahedron, 66, 5833-5840 (2010)

In the iodine catalyst described in Non-Patent Document 1, separation of the product after completion of the reaction and the catalyst used requires a liquid separation operation and a column operation, which are complicated. Therefore, an object of the present invention is to develop an iodine catalyst that can be easily separated and recovered from the product.

Magnetic iron nanoparticles such as magnetite are insoluble in most organic solvents. For this reason, when an iodine catalyst is bonded to the surface of the magnetic iron nanoparticles, a heterogeneous catalyst is generated.
In general, a heterogeneous catalyst is easier to recover after completion of the reaction than a homogeneous catalyst. That is, the catalyst can be easily separated after the reaction by filtration or the like. On the other hand, it is known that the reactivity of a heterogeneous catalyst is lower than that of a homogeneous catalyst. However, since magnetic iron nanoparticles have a very large surface area per unit weight, they have reactivity comparable to homogeneous catalysts. Furthermore, since the magnetic iron nanoparticles have a property of sticking to the magnet, the recovery of the catalyst after completion of the reaction can be achieved by adsorbing it to the magnet from the outside, and no filtration operation is required. A highly reactive catalyst that incorporates an iodine catalyst on the surface of magnetic iron nanoparticles with such properties and has been created easily from the reaction solution.
Hereinafter, the present invention will be described in detail.

In the present invention, unless otherwise specified, an alkyl group means a linear or branched C _1-6 alkyl group such as methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl and the like. , Alkylene is a linear or branched C _1-6 alkylene group such as methylene, ethylene or propylene, and alkyleneoxy group is a linear or branched C1 such as methyleneoxy, ethyleneoxy or isopropyleneoxy. _1-6 alkylene-O— group, alkyleneaminocarbonyl group means linear or branched C _1-6 alkylene-NHCO— group such as methyleneaminocarbonyl, ethyleneaminocarbonyl, isopropyleneaminocarbonyl, alkoxysilyl The groups mean groups such as methoxysilyl and ethoxysilyl, respectively.

The present invention is a magnetic iron nanoparticle-supported iodine catalyst of the following general formula [1].

“Wherein M represents magnetic iron nanoparticles, m represents an integer of 1 to 6, R ^a represents an alkoxysilyl group or phosphonyl group, and R ^b represents any one of the following formulae: .
(In the formula, R ^bb means an alkyleneoxy group or an alkyleneaminocarbonyl group.)

Examples of the magnetic iron particles of M in the general formula [1] include magnetite (Fe ₃ O ₄ ), maghemite (γ-Fe ₂ O ₃ ), and ferrite, with magnetite being preferred.

The size of the magnetic iron particles is nano-sized, and the size is 5 to 100 nm, preferably 5 to 20 nm.

The following are mentioned as a more concrete magnetic iron nanoparticle iodine catalyst of this invention.

In the general formulas [1aa] to [1cb], R ^aa represents an alkyl group, R ^bb represents an alkyleneoxy group or an alkyleneaminocarbonyl group, and m represents an integer of 1 to 6, respectively.

The present invention is also a method for producing a corresponding oxo compound by oxidizing alcohols or phenols in the presence of the iodine catalyst represented by the above general formula [1].

More specifically, an alcohol is an organic compound such as an inorganic oxidizing agent such as potassium peroxymonosulfate or an organic compound such as m-chloroperbenzoic acid in the presence of an iodine catalyst represented by the above general formulas [1a] to [1f]. In this method, an oxidant is reacted to produce a corresponding oxo compound.

By using the magnetic iron nanoparticle-supported iodine catalyst of the present invention and performing an oxidation reaction of alcohols or phenols, the corresponding oxo compound can be produced in high yield. Although the reaction activity of the catalyst is almost the same as that of a conventional homogeneous catalyst, the catalyst can be easily separated and recovered by placing a magnet outside the reaction vessel after the reaction is completed.

The magnetic iron nanoparticle carrying | support iodine catalyst of this invention can be manufactured with the following method, for example.

<Production method 1>

“In the formula, M represents magnetic iron nanoparticles, m represents an integer of 1 to 6, R ^a represents an alkoxysilyl group or phosphonyl group, R ^bb represents an alkyleneoxy group or an alkyleneaminocarbonyl group, X Represents a halogen atom such as a chlorine atom.)

The compound of general formula [1a] can be produced by reacting the compound of general formula [2] with the compound of general formula [3] in a solvent in the presence of a base.

Although the base used for this reaction will not be specifically limited if it is used as a base in a normal reaction, For example, N-methylmorpholine, a triethylamine, a diisopropylethylamine, a tributylamine, 1, 8- diazabicyclo [5.4. 0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [5.4.0] undec-7-ene, pyridine, 4- (N , N-dimethylamino) pyridine, or an organic base such as picoline, or an inorganic base such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, or sodium hydride.

The solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane, and pyridine also used as a base. These solvents may be used alone or in combination.
This reaction may be performed at 20 ° C. to 60 ° C. for 30 minutes to 12 hours.

The compound of the general formula [2] may be produced according to a known method, but for example, it can be produced by reacting aminotrialkoxysilane with activated magnetite.
<Production method 2>

“Wherein M represents magnetic iron nanoparticles, m represents an integer of 1 to 6, R ^a represents an alkoxysilyl group or phosphonyl group, and R ^bb represents an alkyleneoxy group or an alkyleneaminocarbonyl group, means.)

A compound of general formula [1b] or general formula [1c] can be produced by subjecting a compound of general formula [4] and a compound of general formula [5a] or general formula [5b] to a click reaction. The click reaction may be performed using a known method or a method similar thereto.

EXAMPLES The present invention will be described more specifically with reference to the following examples, but the present invention is not limited thereto.

Example 1
<Synthesis of magnetite nanoparticles supported iodine catalyst (MC-1)>

(1) 3-Aminopropyltriethoxysilane (122 mg, 0.55 mmol) was added to a suspension of activated magnetite (1.439 g, 6.215 mmol) in ethanol (30 mL) at room temperature (25 ° C.). After heating to 50 ° C. and stirring for 6 hours, a black solid aminosilyloxymagnetite (1.45 g) was obtained from the reaction solution using a magnet. Further, the mother liquor and the washing liquid were concentrated to recover 3-aminopropyltriethoxysilane (51 mg, 42%).

(2) Triethylamine (234 mg, 2.31 mmol) and N, N-dimethyl-4-aminopyridine (DMAP: 19 mg, 0.154 mmol) were added to a suspension of aminosilyloxymagnetite (1.45 g) in methylene chloride (7 mL) at 0 ° C. Added in. 4-Iodophenoxyacetyl chloride (228 mg, 0.77 mmol) was prepared by adding thionyl chloride (0.96 mL) to 4-iodophenoxyacetic acid (214 mg, 0.77 mmol) and heating to reflux. did. After heating up to room temperature (25 degreeC) and stirring for 4 hours, the magnetite nanoparticle carrying | support iodine catalyst was isolate | separated from the reaction liquid using the magnet. The obtained solid was washed with ethanol and air-dried to obtain a black solid magnetite nanoparticle-supported iodine catalyst MC-1 (1.479 g).

Example 2
<Synthesis of magnetite nanoparticles supported iodine catalyst (MC-2)>

(1) A solution of 2-iodobenzoyl chloride (799 mg, 3 mmol) in methylene chloride (3 mL) was mixed with 2-amino-2-methylpropanoic acid hydrochloride (553 mg, 3.6 mmol) and triethylamine (911 mg, 9 mmol) in methylene chloride (7 mL). ) Added to the solution at 0 ° C. and then stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate (50 mL), washed with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried and concentrated. The residue was purified by silica gel column chromatography to obtain 2- (2-iodobenzamido) -2-methylpropanoic acid methyl ester (889 mg, 85%).
Colorless needle crystals (recrystallization solvent: ethyl acetate-hexane).
Melting point: 125-127 ° C

(2) 2- (2-iodobenzamide) -2-methylpropanoic acid methyl ester (889 mg, 2.56 mmol) and lithium hydroxide monohydrate (430 mg, 10.24 mmol) were added to tetrahydrofuran, methanol, and water (25: 8: The mixture was dissolved in a mixed solvent (8) (8 mL) and stirred at room temperature for 30 minutes. The reaction was diluted with water (60 mL) and acidified with 10% hydrochloric acid. After extraction with ethyl acetate, the extract was dried and concentrated to give 2- (2-iodobenzamido) -2-methylpropanoic acid (836 mg, 98%).
Colorless needle crystal (recrystallization solvent: ethyl acetate-hexane)
Melting point: 206-207 ° C.

(3) Triethylamine (357 mg, 3.528 mmol) and N, N-dimethyl-4-aminopyridine (DMAP: 29 mg, 0.235 mmol) were added to a suspension of aminosilyloxymagnetite (1.796 g) in methylene chloride (8 mL) at 0 ° C. Added in. To 2- (2-iodobenzamido) -2-methylpropanoic acid (280 mg, 0.840 mmol) was added thionyl chloride (1.1 mL) and heated to reflux to give 2- (2-iodobenzamido) -2-methylpropanoyl chloride (295 mg). , 0.840 mmol) was slowly added dropwise to the suspension of magnetite. After heating up to room temperature (25 degreeC) and stirring for 4 hours, the magnetite nanoparticle carrying | support iodine catalyst was isolate | separated from the reaction liquid using the magnet. The obtained solid was washed with ethanol and air-dried to obtain a black solid magnetite nanoparticle-supported iodine catalyst MC-2 (1.549 g).

Example 3
<Synthesis of magnetite nanoparticles supported iodine catalyst (MC-3)>

1-iodo-4 prepared according to literature method ²⁾ was added to a suspension (3 mL) of tert-butanol-water (1: 1) of magnetite (300 mg) supported by the linker prepared according to literature method ^1). Add-(2-propynyloxy) benzene (199 mg, 0.77 mmol), copper (II) sulfate pentahydrate (9 mg, 0.035 mmol), sodium ascorbate (21 mg, 0.105 mmol), triethylamine (0.2 mL, 1.4 mmol) It was. After stirring for 24 hours at room temperature (25 ° C.), the magnetite nanoparticle-supported iodine catalyst was separated from the reaction solution using a magnet. The obtained solid was washed 3 times with a mixed solvent of methylene chloride-ether (1: 1), then further washed with ether 3 times, air-dried, and dried with black solid magnetite nanoparticles supported iodine catalyst MC-3 (250 mg). Got.
Literature
1) Tucker-Schwartz AK, Garrell RL Chem. Eur. J., 16, 12718 (2010).
2) Pal M., Parasuraman K., Yeleswarapu KR, Org. Lett., 5, 349 (2003).

Example 4
<Oxidation of 4-methoxyphenol (1)>

Magnetite nanoparticles supported iodine catalyst MC-1 (253 mg, 0.02 mmol: calculated 0.079 mmol / g) of 2-pivaloyloxymethyl-4-methoxyphenol (48 mg, 0.2 mmol) and oxone (123 mg, 0.2 mmol) It was added to 2,2,2-trifluoroethanol (1.3 mL) /0.1 M phosphate buffer (2.6 mL) at room temperature (25 ° C.). After stirring for 2 hours, magnetite nanoparticle-supported iodine catalyst (253 mg, 100%) was recovered using a magnet. The reaction mixture was diluted with ethyl acetate (20 mL), washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 2,2-dimethylpropanoic acid 3,6-dioxocyclohexa-1,4-dienylmethyl ester (38 mg, 86%).
Example 4

<Oxidation of 4-methoxyphenol (2)>

Magnetite nanoparticles supported iodine catalyst MC-3 (56 mg, 0.04 mmol: calculated 0.71 mmol / g) of 2-pivaloyloxymethyl-4-methoxyphenol (48 mg, 0.2 mmol) and oxone (123 mg, 0.2 mmol) The mixture was added to 2,2,2-trifluoroethanol (0.8 mL) / water (0.4 mL) at room temperature (25 ° C.). After stirring for 4 hours, magnetite nanoparticle-supported iodine catalyst (48 mg, 86%) was recovered using a magnet. The reaction mixture was diluted with ethyl acetate (20 mL), washed successively with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 2,2-dimethylpropanoic acid 3,6-dioxocyclohexa-1,4-dienylmethyl ester (40 mg, 91%).

The magnetic iron nanoparticle iodine catalyst of the present invention can be used in the oxidation process of alcohols in the production of fine chemicals such as pharmaceuticals and agricultural chemicals, and the construction of a green industrial plant with little waste can be achieved.

Claims (2)

Iodine catalyst represented by the following general formula
“Wherein M represents magnetic iron nanoparticles, m represents an integer of 1 to 6, R ^a represents an alkoxysilyl group or phosphonyl group, and R ^b represents any one of the following formulae: .
(In the formula, R ^bb means an alkyleneoxy group or an alkyleneaminocarbonyl group.) A method for producing a corresponding oxo compound from alcohols or phenols using the iodine catalyst according to claim 1.