JP5077795B2 - Method for producing carbonyl compound - Google Patents

Description

  The present invention relates to a method for producing a carbonyl compound by oxidizing an alkane compound.

Although the oxidation reaction of alkanes by a combination of iron salt and peroxide has long been known as a Gif system, the use of pyridine solvents and acid additives is essential, and there are few studies on benzylic oxidation. Recently, benzylic oxidation of arylalkanes using t-butyl hydroperoxide as an oxidant using iron (III) chloride as a catalyst has been reported, but it still requires a pyridine solvent and high temperature, and is not activated. In the case of arylalkanes, there is a problem that the yield is extremely low (Non-patent Document 1).
Moreover, about the complex which consists of an iron ion-long-chain alkyl sulfate ion utilized as a catalyst by this invention, the synthesis method, its structure, and the use as a surfactant were known (nonpatent literature 2).

Synth. Catal. 2007, 349, 861 J. Am. Chem. Soc. 1997, 119, 8652

  The present invention further improves the oxidation reaction (Non-patent Document 1) used for the conventional iron (III) chloride catalyst, and oxidizes alkane compounds under mild conditions in water to produce the corresponding ketone compounds in high yield. A method for synthesis and a catalyst therefor are provided.

Although the application of the complex composed of iron ions and long-chain alkyl sulfate ions (Non-patent Document 2) to the catalytic reaction was not known at all, the present inventors used only this complex as an oxidation catalyst, so As a solvent, it was found that a simple arylalkane can be oxidized to a ketone at a low temperature at a low temperature, and the present invention has been completed.
That is, the present invention relates to the following general formula Fe ₂ O (O ₃ SOR ¹ ) _{4 in} water.
(Wherein R ¹ represents a linear or branched hydrocarbon group having 8 to 20 carbon atoms ) and in the presence of an oxygen-bridged dinuclear iron (III) catalyst and an oxidant represented by the following general formula: the formula R _² -CH ² -R ³
(In the formula, R ² and R ³ may be the same or different, and at least one of them represents an optionally substituted aromatic hydrocarbon group or aromatic heterocyclic group, and the remainder is Represents an alkyl group, a cycloalkyl group or an alkenyl group which may have a substituent, and R ² and R ³ may form a 5- or 6-membered ring which may contain a hetero atom. The following general formula R ² —CO—R ³ comprising oxidizing an alkane compound represented by
(Wherein R ² and R ³ are defined in the same manner as described above).

In the production method of the present invention, an arylalkylketone or diarylketone synthesized by a Friedel-Crafts reaction using an acid chloride and a benzene derivative as raw materials usually in the presence of aluminum chloride can be synthesized by direct oxidation of the alkylbenzene derivative. The solvents, oxidizing agents, and catalysts used are all inexpensive and less toxic, and have high industrial utility value.
The production method of the present invention can be used for a novel production process of arylalkyl ketones or diaryl ketones.

The oxygen-bridged dinuclear iron (III) catalyst used in the present invention is represented by the following general formula.
Fe ₂ O (O ₃ SOR ¹ ) ₄
In the formula, R ¹ represents a linear or branched hydrocarbon group having from 8 to 20 carbon atoms, preferably an alkyl group having a carbon number of linear 10 to 16.
This compound has been known as a kind of iron (III) alkylsulfate complex (Non-patent Document 2), and the synthesis method thereof is referred to this document.

The alkane compound which is a substrate for the reaction of the present invention is represented by the following general formula.
R ² —CH ₂ —R ³
In the formula, R ² and R ³ may be the same or different, and at least one represents an aromatic hydrocarbon group or an aromatic heterocyclic group which may have a substituent. Therefore, both R ² and R ³ may be an aromatic hydrocarbon group or an aromatic heterocyclic group which may have a substituent.
In the synthesis method of the present invention, it is essential that at least one bonding group bonded to an alkane (that is, a methylene group) is an aromatic group in order to stabilize a radical on the methylene group. Become.
Examples of the aromatic hydrocarbon group include an aryl group, and examples of the aryl group include a phenyl group and an α or β-naphthyl group. Aromatic heterocyclic groups include monocyclic aromatic heterocyclic groups such as pyridyl, pyrimidinyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, furyl, imidazolyl, benzisothiazolyl, benzisoxazolyl, benzfuryl, quinolyl, isoquinolyl And bicyclic aromatic heterocyclic groups such as indolyl, indazolyl, benzimidazolyl, benzoxazolyl, naphthyridinyl, pteridinyl, thienofuranyl, imidazothiophenyl, and imidazolofuranyl.
These may have a substituent and are not particularly limited, and examples thereof include a linear or branched alkyl group, an alkoxyl group, an aryl group, and a halogen atom.

Residual (i.e., at R ² or R ^3, means a non-aromatic hydrocarbon group or an aromatic heterocyclic group.) May have a substituent, A alkyl group, a cycloalkyl group or an alkenyl group by weight, preferably alkyl groups. The alkyl group may be linear or branched and is not particularly limited, but usually has 1 to 20 carbon atoms. Examples of the cycloalkyl group include cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl groups. Examples of the alkenyl group include a vinyl group, a propenyl group, a 1-methylvinyl group, and an allyl group.
These may also have the same substituents as described above.
R ² and R ³ may together form a 5- or 6-membered ring that may contain a heteroatom. Examples of the hetero atom include —O—, —S—, and —NH—.

The solvent of the synthesis method of the present invention is water. The solvent may be substantially water and may contain about 10% by volume of a solvent compatible with water such as alcohol, acetone, tetrahydrofuran, and acetonitrile.
Examples of the oxidizing agent used in the present invention include hydroperoxide (ROOH, where R = tBu, PhC (Me) _2- , MeCO-, PhCO-, etc.), dialkyl peroxide (ROOR, where R = tBu, PhC (Me) _2- And diacyl peroxide (ROOR, where R = MeCO-, PhCO-, etc.).
The concentration of the substrate is usually 0.1 to 2M.
The concentration of the oxidizing agent is usually 1.0 to 10M.
The reaction temperature is usually 0-50 ° C. It is one of the features of the present invention that the alkane compound can be oxidized at such a low temperature.
The reaction time is usually 24 to 72 hours.

As a result of this oxidation reaction, the methylene group at the benzyl position where the radical is stabilized is most preferentially oxidized, and a carbonyl compound represented by the following formula corresponding to the alkane compound is obtained.
R ² —CO—R ³
(Wherein R ² and R ³ are as defined above.)

The following examples illustrate the invention but are not intended to limit the invention.
In this example, ¹ H NMR and ¹³ C NMR are measured using an NMR measuring instrument (JEOL JNM-ECX-400, JNM-ECX-500 or JNM-ECX-600) with CDCl ₃ as a solvent and tetramethylsilane ( (δ = 0, ¹ H NMR) or CDCl ₃ (δ = 77.0, ¹³ C NMR) was measured as an internal standard substance. Silica gel 60 (Merck) was used for column chromatography and Wakogel B-5F was used for preparative thin layer chromatography.

Production Example 1
In this production example, Fe ₂ O (DS) ₄ · 10H ₂ O was synthesized according to the literature (J. Am. Chem. Soc. 1997, 119, 8652) and used as a catalyst in the following examples.
Dissolve Fe (NO ₃ ) ₃ · 9H ₂ O (3.0 g, 7.4 mmol) in 30 mL of water at room temperature. To this solution was added an aqueous solution of sodium dodecyl sulfate (6.4 g, 22.3 mmol / 90 mL), and a yellow solid precipitated immediately. After stirring for 1 hour, the solid was collected by filtration, washed with water several times until no foaming was seen to remove excess sodium dodecyl sulfate adhering to the solid, and dried at room temperature under reduced pressure (ca. 5 mmHg). Then, 2.4 g (1.8 mmol) of Fe ₂ O (DS) ₄ · 10H ₂ O was obtained as a bright yellow solid powder. Yield 49%. Elemental analysis: Calculated as C ₄₈ H ₁₂₀ Fe ₂ O ₂₇ S ₄ C: 42.10, H: 8.83; Experimental C: 41.97, H 8.45

表１に示すアリールアルカン化合物（0.5 mmol）と、製造例１で得たFe₂O(DS)₄ ・10H₂O (17 mg, 0.0125 mmol)を純水 (0.5 mL) 中で良くかき混ぜ、70% t-ブチルヒドロペルオキシド（和光純薬工業株式会社）水溶液(0.34 mL, 2.5 mmol)を加える。反応液を30℃にて50時間撹拌後、飽和炭酸水素ナトリウム（ナカライテスク）水溶液(0.2 mL) を加えて反応を停止した。反応液をジエチルエーテルで3回抽出し、有機層を無水硫酸マグネシウムで乾燥後、ろ過、減圧濃縮し、粗生成物を得た。薄層クロマトグラフィー（展開溶媒：n-ヘキサン／酢酸エチル＝19/1）により精製し、目的とするケトンを得た。
結果を下表に示す。

Examples 1-10
In these examples, the arylalkane compound was oxidized according to the following formula using the catalyst synthesized in Production Example 1 to synthesize the corresponding ketone (wherein R ¹ is an aryl group).

The arylalkane compound (0.5 mmol) shown in Table 1 and Fe ₂ O (DS) ₄ · 10H ₂ O (17 mg, 0.0125 mmol) obtained in Production Example 1 were mixed well in pure water (0.5 mL). Add% t-butyl hydroperoxide (Wako Pure Chemical Industries, Ltd.) aqueous solution (0.34 mL, 2.5 mmol). The reaction solution was stirred at 30 ° C. for 50 hours, and then saturated sodium hydrogen carbonate (Nacalai Tesque) aqueous solution (0.2 mL) was added to stop the reaction. The reaction solution was extracted three times with diethyl ether, and the organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. Purification by thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 19/1) gave the desired ketone.
The results are shown in the table below.

Hereinafter, the source of the arylalkane compound used in the above Examples and the analysis results of the purified product are shown. Some compounds were synthesized according to the literature (Reference 1: Org. Lett. 2004, 6, 1297, Reference 2: Chem. Ber. 1985, 118, 1050., Reference 3: Synthesis 2007, 2249.).
(1) Example 1:
Arylalkane compounds: n-octylbenzene (Tokyo Chemical Industry)
Products: 1-phenyloctan-1-one (1a) ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.96 (d, J = 7.6 Hz, 2H), 7.55 (t, J = 7.6 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 2.96 (t, J = 7.4 Hz, 2H), 1.73 (m, 2H), 1.39-1.20 (m, 8H), 0.88 (t, J = 6.4 Hz, 3H ¹³ C NMR (100 MHz, CDCl ₃ ): δ 200.5, 137.0, 132.8, 128.5, 128.0, 38.6, 31.7, 29.3, 29.1, 24.3, 22.6, 14.0.
(2) Example 2:
Arylalkane compound: 1- (4-methoxyphenyl) octane (synthesized according to the method described in Reference 1)
Product: 1- (4-methoxyphenyl) octan-1-one (1b). ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.94 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 3.86 (s, 3H), 2.90 (t, J = 7.4 Hz, 2H), 1.72 (m, 2H), 1.37-1.20 (m, 8H), 0.88 (t, J = 6.8 Hz, ¹³ C NMR (100 MHz, CDCl ₃ ): δ 199.2, 163.2, 130.2, 130.1, 113.6, 55.4, 38.2, 31.7, 29.3, 29.1, 24.6, 22.6, 14.0.
(3) Example 3:
Arylalkane compound: 1- (4-fluorophenyl) octane (synthesized according to the method described in Reference 1)
Products: 1- (4-Fluorophenyl) octan-1-one (1c). ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.01-7.96 (m, 2H), 7.15-7.10 (m, 2H), . 2.93 (t, J = 7.4 Hz, 2H), 1.73 (m, 2H), 1.41-1.20 (m, 10H), 0.88 (t, J = 6.6 Hz) 13 C NMR (100 MHz, CDCl 3): δ 198.9, 165.5 (d, JCF = 253.9 Hz), 133.4 (d, JCF = 2.9 Hz), 130.6 (d, JCF = 8.6 Hz), 115.5 (d, JCF = 22.1), 38.5, 31.7, 29.3, 29.1, 24.3 , 22.6, 14.0.
(4) Example 4:
Arylalkane compound: 1- (4-t-butylphenyl) octane (synthesized in the same manner as described in Document 1)
Product: 1- (4-t-butylphenyl) octan-1-one (1d). ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.90 (d, J = 8.0, 2H), 7.47 (d, J = 8.0, 2H), 2.94 (t, J = 7.4 Hz, 2H), 1.72 (m, 2H), 1.38-1.21 (m, 19H), 0.88 (t, J = 7.0, 3H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 200.3, 156.5, 134.5, 128.0, 125.4, 38.5, 35.0, 31.7, 31.1, 29.3, 29.1, 24.5, 22.6, 14.1.

(5) Example 5:
Arylalkane compound: 4-pentylbiphenyl (Wako Pure Chemical Industries, Ltd.)
Product: 1-[(1,1'-biphenyl)]-4-yl-1-pentanone (1e). ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.03 (d, J = 8.0 Hz, 2H) , 7.68 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 6.8 Hz, 2H), 7.49-7.37 (m, 3H), 2.99 (t, J = 7.2 Hz, 2H), 1.75 (m, . 2H), 1.43 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H) 13 C NMR (100 MHz, CDCl 3): δ 200.2, 145.5, 139.9, 135.7, 128.9, 128.6, 128.1, 127.2, 127.1, 38.3, 26.5, 22.5, 13.9.
(6) Example 6:
Arylalkane compound: 1,1-dimethylindane (synthesized according to the method described in Document 2)
Product: 3,3-dimethyl-1-indanone (1f). ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.70 (d, J = 7.2. 1H), 7.62 (m, 1H), 7.50 (d, . J = 7.6, 1H), 7.37 (m, 1H), 2.60 (s, 2H), 1.42 (s, 6H) 13 C NMR (100 MHz, CDCl 3): δ 206.0, 163.8, 135.2, 134.9, 127.3, 123.5, 123.2, 52.8, 38.4, 29.9.
(7) Example 7:
Arylalkane compound: 1,1-dimethyl-1,2,3,4-tetrahydronaphthalene (synthesized according to the method described in Document 2)
Product: 4,4-dimethyl-1-tetralone (1 g). ¹ H NMR (400 MHz, CDCl ₃ ): δ 8.02 (dd, J = 8.0, 1.2, 1H), 7.53 (dt, J = 8.0, 1.6 , 1H), 7.42 (dd, J = 7.6, 0.8, 1H), 7.29 (dt, J = 7.8, 1.2, 1H), 2.73 (t, J = 7.0 Hz, 2H), 2.03 (t, J = 7.0 Hz , 2H), 1.40 (s, 6H) 13 C NMR (100 MHz, CDCl 3):. δ 198.4, 152.2, 133.8, 131.0, 127.2, 126.2, 125.8, 37.0, 35.0, 33.8, 29.7.
(8) Example 8:
Arylalkane compound: 2,2-dimethylchroman (synthesized according to the method described in Reference 3)
Product: 2,3-dihydro-2,2'-dimethylchromen-4-one (1h). ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.86 (dd, J = 7.6, 1.8 Hz, 1H), 7.47 (m, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 2.73 (s, 2H), 1.47 (s, 6H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 192.4, 159.8, 136.0, 126.4, 120.5, 120.0, 118.2, 79.0, 48.7, 26.5.
(9) Example 9:
Arylalkane compound: Fluorene (Wako Pure Chemical Industries, Ltd.)
Product: 9-fluorenone (1i). ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.65 (brd, J = 7.2 Hz, 2H), 5.52-7.46 (m, 4H), 7.29 (dt, J = 7.2 , 1.6 Hz, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 193.8, 144.3, 134.6, 134.0, 128.9, 124.1, 120.2.
(10) Example 10:
Arylalkane compounds: Diphenylmethane (Nacalai Chemical)
Products: Benzophenone (1j). ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.81 (d, J = 7.6 Hz, 4H), 7.60 (t, J = 7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz, 4H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 196.6, 137.4, 132.3, 129.9, 128.2.

Claims (3)

In water, the following general formula Fe ₂ O (O ₃ SOR ¹ ) ₄
(Wherein R ¹ represents a linear or branched hydrocarbon group having 8 to 20 carbon atoms ) and in the presence of an oxygen-bridged dinuclear iron (III) catalyst and an oxidant represented by the following general formula: the formula R _² -CH ² -R ³
(In the formula, R ² and R ³ may be the same or different, and at least one of them represents an optionally substituted aromatic hydrocarbon group or aromatic heterocyclic group, and the remainder is Represents an alkyl group, a cycloalkyl group or an alkenyl group which may have a substituent, and R ² and R ³ may form a 5- or 6-membered ring which may contain a hetero atom. The following general formula R ² —CO—R ³ comprising oxidizing an alkane compound represented by
(Wherein R ² and R ³ are defined in the same manner as described above). The production method according to claim 1, wherein at least one of R ² and R ^{3 is} an aryl group which may have a substituent. The following general formula Fe ₂ O (O ₃ SOR ¹ ) ₄
(Wherein R ¹ represents a linear or branched hydrocarbon group having 8 to 20 carbon atoms ), a catalyst for oxidizing a alkane compound to synthesize a corresponding ketone compound .