JPH1112218A - Production of alpha-alkylbenzyl methyl ketone derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject derivative that is useful as a synthetic intermediate for agrochemicals and medicine by reaction of a Grignard reagent with an α-haloketone in a preferably mixed solvent system. SOLUTION: The objective derivative of formula III is obtained by reaction of 1 mole of Grignard reagent of formula I [R<1> is a 1-8C alkyl, a substituted 1-2C alkyl; X<1> is Cl, Br, I] such as 4-methoxyphenylmagnesium bromide, 4- ethoxyphenylmagnesium bromide with 0.95-1.2 mole of an α-haloketone of formula II (R<2> is a 1-8C alkyl; X<2> is Cl, Br, I) such as 3-chloro-2-butanone, 3-chloro-2- pentanone) in a mixed solvent of an etheric solvent as diethyl ether or tetrahydrofuran and a hydrocarbon solvent as benzene, toluene or xylene at a volume ratio of 1/1-1/10.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing an α-alkyl-benzylmethyl ketone derivative useful as a synthetic intermediate for agricultural chemicals, medicines and the like. α-Alkyl-benzyl methyl ketone derivatives are, for example, compounds of the general formula 4 useful as agricultural pesticides.

Embedded image (Wherein, X represents a hydrogen atom or a fluorine atom, R ¹
Has the same meaning as described above. ) (JP-A-62-5928).
(See Reference Example 1 below)

2. Description of the Related Art As a method for producing an α-alkyl-benzyl methyl ketone derivative, a production method represented by the following scheme 5 is known as a known method. (J. Am. Chem. So
c. , 80, 4556 (1958))

Embedded image However, the production method is not satisfactory in terms of yield, and development of a more efficient production method is desired.

According to the present invention, as means for solving the above problems, there are provided: General formula 6

Embedded image (Wherein, R ¹ represents a C1-C8 alkyl group or a C1-C2 alkyl group substituted with one or more fluorine atoms;
¹ represents a chlorine atom, a bromine atom or an iodine atom. ) And a Grignard reagent represented by the general formula

Embedded image (Wherein, R ² represents a C1-C8 alkyl group, and X ² represents a chlorine atom, a bromine atom or an iodine atom), and an ether- and hydrocarbon-based mixed solvent of an α-haloketone compound represented by the formula: General formula by reacting in a system

Embedded image (Wherein, R ¹ and R ² have the same meanings as described above). 2. The above-mentioned production method, wherein the Grignard reagent represented by the general formula (6) is supplied to the reaction system as a solution in an ether-based solvent. 3. The process according to the above, wherein the α-haloketone compound represented by the general formula 7 is supplied to the reaction system as a solution of a hydrocarbon solvent. 4. The above-mentioned production method by dropping an ether-based solution of a Grignard reagent represented by the general formula 6 into a hydrocarbon-based solution of an α-haloketone compound represented by the general formula 7: 5. The above-described production method, wherein a hydrocarbon solution of the α-haloketone compound represented by the general formula (7) and an ether solution of a Grignard reagent represented by the general formula (6) are co-injected into the reaction system. 6. The above-mentioned method by co-injecting a hydrocarbon-based solution of an α-haloketone compound represented by the general formula 7 and an ether-based solution of a Grignard reagent represented by the general formula 6 into a hydrocarbon-based solvent. Manufacturing method. I will provide a.

[0002]

BEST MODE FOR CARRYING OUT THE INVENTION In the method of the present invention, the C1-C8 alkyl group represented by R ¹ is a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group,
Examples of the C1 to C2 alkyl group substituted with one or more fluorine atoms include a difluoromethyl group, a trifluoromethyl group, and a pentafluoroethyl group. (Where "n" represents "normal" and "s" represents "secondary"; the same applies hereinafter)
The C1~C8 alkyl group represented by R ^2, a methyl group, an ethyl group, n- propyl group, an isopropyl group, n-
Examples thereof include a butyl group and an s-butyl group.

Hereinafter, the present invention will be described in detail. In the method of the present invention, examples of the hydrocarbon solvent include aromatic hydrocarbons such as benzene, toluene, and xylene, and examples of the ether solvent include diethyl ether and tetrahydrofuran. In the reaction system according to the method of the present invention, the volume ratio between the ether solvent and the hydrocarbon solvent is from 1: 1 to 1:10. The amount of the reagent used in the reaction is usually 0.8 to 2.0 moles of the α-haloketone compound represented by the general formula 7 per mole of the Grignard reagent represented by the general formula 6 Preferably, the ratio is 0.95 to 1.2 mol. The reaction temperature range is usually from 0 ° C to 10 ° C during the dropwise addition of the Grignard reagent, and is usually from 30 ° C to 10 ° C after the dropwise addition of the Grignard reagent.
130 ° C., preferably 30 ° C. to 110 ° C. After the completion of the Grignard reagent, the reaction time range is
Usually 2 to 6 hours. After completion of the reaction, the reaction solution is poured into dilute acidic water such as dilute hydrochloric acid, and subjected to ordinary post-treatment operations such as extraction with an organic solvent and concentration to obtain an α-alkyl-benzylmethyl compound represented by the general formula (8). A ketone derivative can be obtained. Further, the compound can be purified, if necessary, by means such as distillation and chromatography. The Grignard reagent represented by the general formula 6 can be prepared according to a known method. (See Reference Example 2 described below.) As the α-haloketone compound represented by the general formula (7), a commercially available α-haloketone compound may be used, or the α-haloketone compound may be produced from the corresponding commercially available ketone compound by halogenation according to a known method. Can be. (For example, chlorination is described in J. Org. Ch.
em. 1985, 50, 1599. : Bromination is Tetr
ahedron Letters. 1984, 25, 3
369. : Iodination was performed according to Synthesis. 1986,
678. reference)

The α-alkyl-benzylmethyl ketone derivative represented by the general formula 8 obtained by the present production method, the Grignard reagent represented by the general formula 6 used in the present production method, and the general formula 7 Examples of the α-haloketone compounds are shown below, but the present invention is not limited to these. Α-alkyl-benzyl methyl ketone derivative represented by the general formula 8 3- (4-methoxyphenyl) -2-butanone 3- (4-ethoxyphenyl) -2-butanone 3- (4-isopropoxyphenyl) -2 -Butanone 3- (4-n-butoxyphenyl) -2-butanone 3- (4-s-butoxyphenyl) -2-butanone 3- (4-trifluoromethoxyphenyl) -2-butanone 3- (4-difluoro Methoxyphenyl) -2-butanone 3- (4-pentafluoroethoxyphenyl) -2-butanone 3- (4-methoxyphenyl) -2-pentanone 3- (4-ethoxyphenyl) -2-pentanone 3- (4- Isopropoxyphenyl) -2-pentanone 3- (4-n-butoxyphenyl) -2-pentanone 3- (4-s-butoxyphe Nyl) -2-pentanone 3- (4-trifluoromethoxyphenyl) -2-pentanone 3- (4-difluoromethoxyphenyl) -2-pentanone 3- (4-pentafluoroethoxyphenyl) -2-pentanone 3- ( 4-methoxyphenyl) -2-hexanone 3- (4-ethoxyphenyl) -2-heptanone 3- (4-ethoxyphenyl) -4-methyl-2-pentanone

The Grignard reagent represented by the general formula: 4-methoxyphenylmagnesium bromide 4-ethoxyphenylmagnesium bromide 4-n-propoxyphenylmagnesium bromide 4-isopropoxyphenylmagnesium bromide 4-n-butoxyphenylmagnesium bromide 4 -S-butoxyphenyl magnesium bromide 4-trifluoromethoxyphenyl magnesium bromide 4-difluoromethoxyphenyl magnesium bromide 4-pentafluoroethoxyphenyl magnesium bromide 4-methoxyphenyl magnesium chloride 4-ethoxyphenyl magnesium chloride 4-n-propoxyphenyl magnesium chloride 4-isopropoxyphenylmagnesium chloride 4-n-butoxyfe Le chloride 4-s-butoxyphenyl chloride 4-trifluoromethoxyphenyl magnesium chloride 4-difluoromethoxy-phenyl magnesium chloride 4-pentafluorophenyl-ethoxyphenyl chloride

The α-haloketone compound represented by the general formula (7) 3-chloro-2-butanone 3-chloro-2-pentanone 3-chloro-2-hexanone 3-chloro-4-methyl-2-pentanone 3-chloro- 2-heptanone 3-bromo-2-butanone 3-bromo-2-pentanone 3-bromo-2-hexanone 3-bromo-4-methyl-2-pentanone 3-bromo-2-heptanone

The compound represented by the general formula 8 can be derived, for example, by the following method. First, a compound represented by the following general formula:

Embedded image (Wherein, X represents the same meaning as described above), by reacting the compound with a compound represented by the following formula in a solvent in the presence of a phase transfer catalyst and an alkali metal hydroxide.

Embedded image (Wherein X and R ¹ represent the same meaning as described above). The reaction temperature range of the reaction is usually 0 ° C.
To 120 ° C, preferably from 10 ° C to 60 ° C.
The range of the reaction time is usually 0.5 hour to about 72 hours.
The amount of the reagent used for the reaction is such that the compound represented by the general formula 9 is based on 1 mol of the compound represented by the general formula 8
The ratio is usually 0.5 to 10 mol, preferably 1 to 1.5 mol, and the alkali metal hydroxide is usually 1 to 20 mol.
The molar ratio is preferably 1.5 to 10 mol, and the phase transfer catalyst is usually 0.001 to 0.5 mol, preferably 0.01 to 0.1 mol. Examples of the alkali metal hydroxide include sodium hydroxide and potassium hydroxide. Alkali metal hydroxides can be used in aqueous solutions, flakes or powders,
It is preferably used in flake or powder form. Examples of the phase transfer catalyst include tetra-n-butylammonium chlorinated, tetra-n-butylammonium bromide, tetra-n-butylammonium iodide, N-benzyltrimethylammonium hydroxide, tetra-n-butylammonium hydrogen sulfate, chlorine And tertiary amines such as tris [2- (2-methoxyethoxy) ethyl] amine.
Examples of the solvent include aromatic hydrocarbons such as toluene, xylene and monochlorobenzene, aliphatic hydrocarbons such as hexane and heptane, and mixtures thereof.
After completion of the reaction, the reaction solution is subjected to ordinary post-treatment operations such as extraction with an organic solvent and concentration to obtain the compound represented by the general formula (10). Further, the compound can be purified, if necessary, by means such as column chromatography.

Next, a compound represented by the general formula (10), a chlorine compound selected from the group consisting of phosphorus oxychloride, carbonyl chloride, oxalyl chloride, phosphorus pentachloride, pyrophosphoric chloride and phosphorus trichloride, and N, N-dimethyl After reacting with an amide compound selected from the group consisting of formamide and N-methylformanilide, the product of the reaction is hydrolyzed to give a compound of the general formula 1
1

Embedded image (Wherein X and R ¹ have the same meanings as described above). The reaction is carried out in a system with N,
N-dimethylformamide or N-methylformanilide reacts with the above chlorine compound, and the reactant is represented by the general formula
It proceeds by reacting with the compound shown in Chemical formula 10. As a form of the reaction, the reaction product is prepared in advance,
A method of reacting the compound with the compound represented by the general formula (10), or a method of mixing the respective reactants to form the above-described reactant in the system, and allowing the compound to react with the compound represented by the general formula (10) Any method may be employed depending on the purpose. In the reaction, a halogenated hydrocarbon solvent such as dichloromethane, 1,2-dichloroethane or the like, or an aromatic hydrocarbon solvent such as toluene or monochlorobenzene can be used as a reaction solvent, but it is usually a reaction reagent. It is carried out by using an excess amount of N, N-dimethylformamide or N-methylformanilide and using this as a solvent. The amount of the reagent used in the reaction is 1 to 2 moles of the compound represented by the general formula, and the amount of the chlorine compound is 2 to 50 moles, preferably 2.5 to 10 moles. , N-dimethylformamide or N-methylformanilide is from 1 to 5
The ratio is 00 mol, preferably 10 to 200 mol. The temperature range of the reaction is usually 5 ° C to 100 ° C, preferably 15 ° C to 70 ° C, more preferably 15 ° C to 35 ° C. The range of the reaction time is usually 1 hour to 200 hours. Phosphorus trichloride is preferred as the chlorine compound. In the hydrolysis treatment, the reaction solution obtained by the above reaction is poured into water, or after pouring into water, neutralized with a base or an aqueous solution thereof, or directly poured into an aqueous solution of a base. It is performed by The amount of water may be at least equimolar to the acid chloride used in the reaction, and usually an excess amount is used. The reaction temperature range is usually 0 ° C to 50 ° C
And preferably in the range of 0 ° C to 30 ° C. The range of the hydrogen ion concentration of the reaction solution after the hydrolysis treatment is usually
The pH is from pH 1 to pH 10, preferably from pH 2 to pH 8. When the reaction solution is poured into water and then neutralized with a base or an aqueous solution thereof, the base used is potassium acetate, sodium acetate, lithium acetate, potassium carbonate, sodium carbonate, lithium carbonate, potassium hydrogen carbonate. , Sodium bicarbonate, potassium hydroxide, sodium hydroxide or lithium hydroxide. When the reaction solution is directly poured into an aqueous solution of a base, it is preferable to use potassium acetate, sodium acetate, lithium acetate, potassium hydrogen carbonate or sodium hydrogen carbonate as the base. After completion of the hydrolysis, the reaction solution is subjected to ordinary post-treatment operations such as extraction with an organic solvent and concentration to obtain the compound represented by the general formula (11).

The compound represented by the general formula (11) thus obtained is purified as it is or, if necessary, is reacted with an alkali metal hydroxide in a solvent to obtain the compound represented by the general formula (1). The compound represented by Formula 4 can be led. The reaction time is usually 10 minutes to 72 hours, and the reaction temperature is usually 5 ° C.
To 150 ° C, preferably 15 ° C to 100 ° C. The amount of the alkali metal hydroxide used for the reaction is represented by the general formula
The ratio is usually 1 to 20 mol, preferably 1 to 10 mol, per 1 mol of the compound represented by 1. Examples of the alkali metal hydroxide include sodium hydroxide and potassium hydroxide. Examples of the solvent include hydrated alcohols such as hydrated ethanol, hydrated ethers such as hydrated dioxane and hydrated tetrahydrofuran, and mixtures thereof. After completion of the reaction, the reaction solution was extracted with an organic solvent,
The compound represented by the general formula 4 can be obtained by performing ordinary post-treatment operations such as concentration. The compound can be purified by column chromatography, if necessary, or by treatment with an adsorbent such as activated carbon, activated clay, activated alumina, and silica gel.

When the compound represented by the general formula (11) is to be purified, the compound may be derivatized into a bisulfite adduct by a column chromatography method or the like, and the adduct may be converted with a low-polarity organic solvent. A washing method can also be adopted. The bisulfite adduct of the compound represented by the general formula 11 can be easily obtained by reacting the compound with sodium bisulfite, potassium bisulfite or the like in a hydroalcoholic solution such as hydroethanol. Next, a low-polarity organic solvent such as hexane and heptane is added to the reaction solution, and a bisulfite adduct can be purified by performing washing operations such as stirring and liquid separation, and then adding an acid or a base to the adduct. By acting, the purified general formula 1
The compound represented by 1 is obtained. The purified bisulfite adduct thus obtained, or a hydroalcoholic solution thereof can be used as it is as a reaction raw material for the above reaction.

[0011]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention. Production Example 1 8.48 g of 3-chloro-2-butanone under a nitrogen stream
(0.0796 mol) and 160 ml of toluene in a tetrahydrofuran solution of 1.0 mol / l of 4-ethoxyphenylmagnesium bromide under ice-cooling.
9.6 ml were added dropwise. Next, stirring was continued at 87 ° C. for 4 hours, and then cooled to room temperature.
20 g were added. After separating the organic layer, the aqueous layer was further extracted twice with 75 ml of toluene. The organic layers were combined, washed and separated with 100 g of saturated saline, dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. This residue was subjected to silica gel column chromatography to give 10.0 g of 3- (4-ethoxyphenyl) -2-butanone (yield 65.
6%). 1 H-NMR (CDCl3 / TMS) δ value (ppm)
7.11 (d, 2H), 6.85 (d, 2H), 4.0
1 (q, 2H), 3.68 (q, 1H), 2.03
(S, 3H), 1.41 (t, 3H), 1.37 (d,
3H)

Production Example 2 Under a nitrogen stream, 14.3 g of 3-chloro-2-butanone
(0.1337 mol) and 270 ml of toluene was added to a solution of 1.0 mol / l of 4-methoxyphenylmagnesium bromide in tetrahydrofuran 13 under ice cooling.
3.7 ml was added dropwise. Next, stirring was continued at 95 ° C. for 4 hours, and then cooled to room temperature.
g was added. After separating the organic layer, the aqueous layer was further extracted twice with 75 ml of toluene. The organic layers were combined, washed and separated with 100 g of saturated saline, dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. This residue was subjected to silica gel column chromatography to give 17.3 g of 3- (4-methoxyphenyl) -2-butanone (yield 72.6).
%). 1 H-NMR (CDCl3 / TMS) δ value (ppm)
7.14 (d, 2H), 6.87 (d, 2H), 3.7
9 (s, 3H), 3.68 (q, 1H), 2.03
(S, 3H), 1.35 (d, 3H)

Production Example 3 Under a nitrogen stream and ice-cooling, 100 ml of toluene
1.45 mol of ethoxyphenylmagnesium bromide
/ L of 55 ml of tetrahydrofuran solution and 3-chloro-
160 mL of a toluene solution of 8.48 g (0.0796 mol) of 2-butanone was co-dropped. Then, stirring was continued at 95 ° C. for 4 hours, then cooled to room temperature, and 5%
100 g of aqueous hydrochloric acid was added. After separating the organic layer, the aqueous layer was further extracted twice with 75 ml of toluene. The organic layers were combined, washed and separated with 100 g of saturated saline, dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. This residue was subjected to silica gel column chromatography to give 3-
11.7 g of (4-ethoxyphenyl) -2-butanone
(Yield: 76.2%).

Production Example 4 Under a nitrogen gas stream and ice-cooling, 4-
2.81 mol of ethoxyphenylmagnesium chloride
/ L of tetrahydrofuran solution in 20 ml and 3-chloro-
5.99 g (0.0562 mol) of 2-butanone and 60 ml of a toluene solution were co-poured and dropped. Then, at 95 ° C., 3
After continuing stirring for an hour, the mixture was cooled to room temperature, and 100 g of 5% hydrochloric acid was added thereto. After separating the organic layer, the aqueous layer was further extracted twice with 75 ml of toluene. The organic layers were combined, washed and separated with 100 g of saturated saline, dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. This residue was subjected to silica gel column chromatography to give 3-
5.84 g of (4-ethoxyphenyl) -2-butanone
(59.4% yield).

Reference Example 1 3- (4-ethoxyphenyl) -6- (4-fluoro-
3-Phenoxyphenyl) -3-methyl-1-hexyne (Example of production of compound described in JP-A-62-25928) (1) 3- (4-ethoxyphenyl) -6- (4-fluoro-3- Preparation of phenoxyphenyl) -3-methylhexane-2-one) 3- (4-ethoxyphenyl) -2-butanone 88.2
g (0.459 mol) and 3- (4-fluoro-3-phenoxy) phenylpropyl bromide 165.9 (0.5
36 mol) was dissolved in 364 g of n-heptane, and 4.6 g (0.014 mol) of tetra-n-butylammonium bromide and 127.3 g (purity: 96) of potassium hydroxide in powder form were dissolved.
%, 2.178 mol) in a nitrogen stream at 20 to 3%.
The mixture was vigorously stirred at 0 ° C. for 48 hours. 454 g of water and 271 g of monochlorobenzene were added to the reaction mixture, and the mixture was separated. The organic layer was washed successively with 500 g of dilute hydrochloric acid, 450 g of saturated aqueous sodium hydrogen carbonate and 560 g of water, and the solvent was distilled off under reduced pressure to give 3- (4-ethoxyphenyl). 20) g of crude product containing 6- (4-fluoro-3-phenoxyphenyl) -3-methylhexane-2-one [pure yield from 3- (4-ethoxyphenyl) -2-butanone 79 %]. 1 H-NMR (CDCl3 / TMS) δ value (ppm)
7.3 to 6.8 (m, 12H), 4.0 (q, 2H),
2.5 to 2.6 (m, 2H), 1.9 to 1.8 (m, 5
H), 1.5-1.2 (m, 8H)

(2) Production of 3-chloro-4- (4-ethoxyphenyl) -7- (4-fluoro-3-phenoxyphenyl) -4-methyl-2-heptenal The above-mentioned 3- (4-ethoxyphenyl) ) -6- (4-Fluoro-3-phenoxyphenyl) -3-methylhexane-2-one (10 g, 0.0180 mol) was dried in 80.0 g (0.59 g) of N, N-dimethylformamide.
22.4 mol), and 12.4 g (0.0903 mol) of phosphorus trichloride was added to this solution under a nitrogen stream at 20 to 30 ° C.
Dropped over minutes. After the completion of the dropwise addition, the mixture was reacted at 25 ° C. for 27 hours. The reaction solution was poured into 80 g of ice water, adjusted to about pH 5 with 120 g of a 20% aqueous sodium acetate solution, and extracted three times with 50 g of diethyl ether. After the diethyl ether layers were combined and washed twice with 100 g of water, the solvent was distilled off under reduced pressure to give 3-chloro-4- (4-ethoxyphenyl) -7- (4-fluoro-3-phenoxyphenyl). 9.) Crude product of 4-methyl-2-heptenal
2 g (83% pure yield) were obtained. 1 H-NMR (CDCl3 / TMS) δ value (ppm) 1
0.3 (d, 1H), 7.3 to 6.8 (m, 12H),
6.2 (d, 1H), 4.1 (q, 2H), 2.5 to
2.6 (m, 2H), 2.1 to 1.8 (m, 2H),
1.6 to 1.4 (m, 11H)

(3) 3- (4-ethoxyphenyl) -6
Production of-(4-fluoro-3-phenoxyphenyl) -3-methyl-1-hexyne 3-Chloro-4- (4-ethoxyphenyl) -7 described above
To a mixture of 1.00 g (0.0015 mol of pure content) of crude product of-(4-fluoro-3-phenoxyphenyl) -4-methyl-2-heptenal and 2.0 g of n-heptane was added ethanol under a nitrogen stream. / Water = 1/1 (w / w)
0.33 g of sodium bisulfite dissolved in 2.0 g
Was added dropwise at room temperature, and the mixture was further stirred at room temperature for 15 minutes. The mixture was allowed to stand and separated, and the lower layer was separated into 1.0 g of n-heptane.
After washing twice with potassium hydroxide (purity 96%).
60 g (0.0103 mol) were added and the reflux temperature (about 77
C.) for 2 hours. After cooling the reaction solution, 3 g of n-heptane and 3 g of water were added and the mixture was separated, and the aqueous layer was further extracted with 3 g of n-heptane three times. The n-heptane layers were combined, washed three times with 6 g of water, and the solvent was distilled off under reduced pressure to give 3- (4
0.57 g (GC purity 79%, yield 74%) of a crude product containing -ethoxyphenyl) -6- (4-fluoro-3-phenoxyphenyl) -3-methyl-1-hexyne was obtained. 1 H-NMR (CDCl3 / TMS) δ value (ppm)
7.4 to 6.8 (m, 12H), 4.0 (q, 2H),
2.5 (brm, 2H), 2.3 (s, 1H), 1.8
~ 1.4 (m, 10H)

Reference Example 2 Preparation Example of Grignard Reagent 1.97 g (0.08117 mol) of magnesium was suspended in 10 ml of tetrahydrofuran and stirred at 40 ° C.
The temperature rose. 4-Bromophenetol was added to the reaction mixture.
A solution of 0g (0.07958 mol) in 69.6 ml of THF was added dropwise, and the mixture was aged at 40 to 50 ° C for 2 to 3 hours. Thereafter, the reaction solution was cooled to room temperature and used as it was in the reaction of the next step.

Comparative Example 1 8.48 g of 3-chloro-2-butanone under a nitrogen stream
(0.0796 mol) and 80 ml of tetrahydrofuran, at room temperature, 79.6 ml of a 1.0 mol / l tetraethoxyfuran solution of 4-ethoxyphenylmagnesium bromide was added dropwise. Next, stirring was continued at 65 ° C. for 3 hours, and then cooled to room temperature, and 120 g of 2.5% hydrochloric acid was added thereto. After separating the organic layer, the aqueous layer was further extracted twice with 75 ml of toluene. Combine the organic layers,
After washing and separating with 100 g of a saturated saline solution, the solution was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. This residue was subjected to silica gel column chromatography to give 3- (4-
4.73 g of ethoxyphenyl) -2-butanone (yield 3
0.9%).

[0020]

By using the reaction of the present invention, an α-alkyl-benzylmethyl ketone derivative useful as an intermediate for agricultural chemicals and medicines can be produced in high yield.

Claims (9)

[Claims] 1. A compound represented by the general formula: (Wherein, R ¹ represents a C1-C8 alkyl group or a C1-C2 alkyl group substituted with one or more fluorine atoms;
¹ represents a chlorine atom, a bromine atom or an iodine atom. ) And a Grignard reagent represented by the following general formula: (Wherein, R ² represents a C1-C8 alkyl group, and X ² represents a chlorine atom, a bromine atom or an iodine atom), and an ether- and hydrocarbon-based mixed solvent of an α-haloketone compound represented by the formula: A general formula characterized by reacting in a system. (Wherein, R ¹ and R ² have the same meanings as described above). 2. The process according to claim 1, wherein the Grignard reagent represented by the general formula 1 is supplied to the reaction system as a solution in an ether solvent. 3. The process according to claim 1, wherein the α-haloketone compound represented by the general formula 2 is supplied to the reaction system as a solution of a hydrocarbon solvent. 4. An ether-based solution of a Grignard reagent represented by the general formula 1 is dropped into a hydrocarbon-based solution of the α-haloketone compound represented by the general formula 1. 2. The production method according to 1. 5. A method according to claim 1, wherein a hydrocarbon solution of the α-haloketone compound represented by the general formula (2) and an ether solution of a Grignard reagent represented by the general formula (1) are co-injected into the reaction system. The method according to claim 1, wherein 6. A hydrocarbon solvent containing an α-haloketone compound represented by the general formula (2) and an ether solution of a Grignard reagent represented by the general formula (1). The method according to claim 1, wherein: 7. The method according to claim 1, wherein the hydrocarbon solvent is benzene, toluene or xylene. 8. The reaction system according to claim 1, wherein the volume ratio of the ether solvent to the hydrocarbon solvent is from 1: 1 to 1:10.
The production method according to 2, 3, 4, 5, 6, or 7. 9. The method according to claim 1, wherein R ¹ is an ethyl group and R ² is a methyl group.