JP2000159699A - Production of 3-(4-chlorophenyl)-1-bromopropane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To safely produce the subject compound in high yield and a high selectivity by efficiently and para-selectively chlorinating 3-phenyl-1- bromopropane using a zeolite catalyst as a catalyst and a dichloroalkane as a reactional solvent. SOLUTION: (A) 3-Phenyl-1-bromopropane is para-selectively chlorinated in the presence of (C) a dichloroalkane (preferably 1,2-dichloroethane, etc.), using (B) a zeolite catalyst (preferably type L zeolite). The reaction is preferably carried out at 40-140 deg.C by using the component B in an amount of 1-20 pts.wt. based on 100 pts.wt. of the component A and the component B in a volume of 0.1-10 vol. based on 1 vol. of the component A. Simple substance chlorine is usually used as a chlorinating agent in a molar amount of 0.5-1 based on 1 mol of the component A. The reaction is usually conducted in the liquid phase by a batch method. The component A is preferably prepared by a Grignard reaction of a halogenobenzenemagnesium with 1,3-dibromopropane.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing 3- (4-chlorophenyl) -1-bromopropane.
Specifically, 3-phenyl-1-bromopropane is para-selectively chlorinated to give 3- (4-chlorophenyl) -1-.
The present invention relates to a method for producing bromopropane. 3- (4-Chlorophenyl) -1-bromopropane is useful as an intermediate for pharmaceuticals and pesticides.

[0002]

2. Description of the Related Art Conventionally, 3- (4-chlorophenyl) -1
-Bromopropane is 3- (4-chlorophenyl) -1
-Propanol was prepared by using triphenylphosphine and bromine (JP-A-4-287086 and JP-A-2-289579; yield: 49%), phosphorus tribromide (JP-A-2-5023).
No. 81; 65% yield) and hydrobromic acid [J. Che
m. Soc. , P. 1548 (1964); 80% yield].
It is manufactured by bromination with reagents such as The intermediate 3- (4-chlorophenyl) -1-propanol has p
-Chlorobenzyl chloride treated with Mg and then reacted with ethylene oxide [J. Chem. So
c. , P. 1548 (1964); 75% yield / JP-A-2
And a method of reducing 3- (4-chlorophenyl) propionic acid with borane (Japanese Patent Application Laid-Open Nos. 4-24786 and 2-289579).
No., each publication is already known.

[0003] However, the conventional production methods require borane, p-chlorobenzyl chloride, ethylene oxide, etc., which require a large facility load in terms of safety and toxicity, and require expensive raw materials or reagents. However, it is not satisfactory as an industrial production method such as low yield. Moreover, 3- (4-chlorophenyl) -1- was obtained by the chlorination reaction of 3-phenyl-1-bromopropane.
No example of a method for producing bromopropane has been known so far. Generally, a p-chloro monosubstituted benzene derivative is produced by liquid-phase chlorination of a monosubstituted benzene derivative under a Lewis acid catalyst. For example, a method in which sulfur or selenium is used in the presence of Lewis acid, or a thianthrene compound (JP-A-52-19630),
Phenoxatin compounds (JP-A-57-175133), phenothiazine compounds (French patent 254500)
Some attempts have been made to enhance p-selectivity using a modified Lewis acid, such as a method using a heterocyclic compound in the presence of a heterocyclic compound such as that described in Japanese Patent Application Laid-Open No. 4 (1994) -104.

Recently, several attempts have been made to use zeolite as a catalyst, that is, to selectively produce a p-isomer having a small molecular diameter by utilizing the shape selectivity of zeolite. For example, JP-A-59-130227
And JP-A-59-144722 disclose a liquid phase chlorination method of various benzene derivatives using L-type zeolite or Y-type zeolite. Further, there has been reported an example in which the effect of a solvent is proposed in a chlorination reaction of toluene using a zeolite catalyst. For example, a method of chlorinating in the presence of m-dinitrobenzene (Japanese Patent No. 27372)
No. 89) and a method for producing parachlorotoluene by chlorination in the presence of methylene chloride and / or chloroform (Japanese Patent Application Laid-Open No. 3-120232). According to JP-A-3-81235, other halogenated hydrocarbons such as carbon tetrachloride, 1,1,1-trichloroethane, 1,2-dichloroethane, 1,2-dichloropropane, perchloroethane, perchloroethane Ethylene and the like have not been particularly effective.

[0005] The starting material of the present invention, 3-phenyl-
As for 1-bromopropane, triphenylphosphine having 3-phenyl-1-propanol supported on a polymer and bromine [J. Chem. Soc. PerkinI,
2, 195 (1984)], phosphorus tribromide [J. Ch
em. Sco. , P. 2509 (1923)] and hydrobromic acid [Bull. Chem. Soc. Jpn. , 49
Vol., P. 3280 (1976)], and a bromination method has already been reported. However, there are inconveniences such as the raw material alcohol being expensive, not being distributed on the market, and the yield being low. In addition, Friedel-Crafts reaction of benzene with 3-chloro-1-bromopropane [Z
h. Obshich. Kim. 10, 1075 (1940)], and converting allylbenzene in the presence of hydrobromic acid.
Oxidation with diacetyl peroxide [Ann. Ch
im. (Paris), vol. 13, p. 43 (1959)]
However, there are inconveniences such as that the raw materials and the reagents used are expensive, and the equipment load is large in terms of safety and toxicity. That is, 3-phenyl-1
-A practical production method for bromopropane has not been reported so far.

[0006]

DISCLOSURE OF THE INVENTION The present inventors have been concerned with chlorination of 3-phenyl-1-bromopropane with a solvent-free chlorination reaction using zeolite (JP-A-59-1302).
No. 27), a method of chlorination in the presence of m-dinitrobenzene (Japanese Patent No. 2737289) and a method of chlorination in the presence of methylene chloride and / or chloroform (Japanese Patent Application Laid-Open No. 3-120232). Although the conventional method was additionally tested and examined, this compound has highly reactive bromine in the benzene ring side chain, and its molecular diameter is larger than that of a known alkylbenzene, so that the para-selectivity has a selectivity of 66 to 66.
70% (see Comparative Example) is not sufficient, and is not industrially satisfactory. An object of the present invention is to provide 3-phenyl-
An object of the present invention is to provide a method for efficiently and paraselectively chlorinating 1-bromopropane. Another object of the present invention is to provide a method for producing 3- (4-chlorophenyl) -1-bromopropane that incorporates an improved method for producing 3-phenyl-1-bromopropane as a raw material.

[0007]

Means for Solving the Problems As a result of intensive studies in view of such circumstances, the present inventors have conducted chlorination of 3-phenyl-1-bromopropane using a specific catalyst in a specific solvent. As a result, para-selectivity is improved, and 3-phenyl-1-bromopropane as a raw material can be obtained in high selectivity and high yield by applying a Grignard reaction using inexpensive halogenated benzene as a starting material. That the present invention was completed

[0008] That is, the gist of the present invention is to provide 3- (4-)-chlorinating of 3-phenyl-1-bromopropane in a para-selective manner in the presence of dichloroalkane using a zeolite catalyst. 1. A method for producing (chlorophenyl) -1-bromopropane, Item 3. The zeolite according to item 1, wherein the zeolite is an L-type zeolite.
2. a method for producing-(4-chlorophenyl) -1-bromopropane; (A) Magnesium halogenobenzene and 1,3-
Dibromopropane is subjected to a Grignard reaction to give 3-phenyl-1-bromopropane. (B) Then, the obtained 3-phenyl-1-bromopropane is converted into a paraffin using a zeolite catalyst in the presence of dichloroalkane. A method for producing 3- (4-chlorophenyl) -1-bromopropane, which is selectively chlorinated. 4. 3. The chlorobenzene produced as a by-product in the step (b) is separated and used in the step (a).
A method for producing (4-chlorophenyl) -1-bromopropane. 5. 3. The reaction of step (a) is carried out in the presence of a copper compound and a lithium compound.
A method for producing (chlorophenyl) -1-bromopropane. Hereinafter, the inventions of claims 1 and 2 will be described as invention (I), and the inventions of claims 3, 4 and 5 will be described as invention (II).

[0009]

DESCRIPTION OF THE PREFERRED EMBODIMENTS First, the invention (I) will be described. The zeolite used as a catalyst in the production method of the present invention may be any zeolite as long as its structure is not deteriorated by generated hydrogen chloride and other acidic substances, for example, mordenite zeolite, ZSM zeolite, β zeolite, L-type zeolites, Y-type zeolites and the like can be mentioned. Among them, L-type zeolite is particularly preferably used. The exchangeable cation of zeolite is not particularly limited. Specific examples of the cation generally include sodium and potassium, but other cations such as calcium, magnesium and proton may be included. These cations can be easily exchanged by a known ion exchange method, for example, by impregnating zeolite in an aqueous solution containing them. The zeolite may be in the form of powder or pellets, but is usually used as it is. In the method of the present invention, the amount of zeolite used is 0.1 to 30 parts by weight, preferably 1 to 20 parts by weight, based on 100 parts by weight of 3-phenyl-1-bromopropane.

In the method of the present invention, the dichloroalkane used is not particularly limited as long as it is a saturated hydrocarbon having two chloro groups in the molecule. It may be either branched or may have a cycloalkyl group in the molecule. Specific examples of the dichloroalkane compound include, for example, 1,1-dichloroethane, 1,2-dichloroethane, 1,1-dichloropropane, 1,2-dichloropropane, 2,2-dichloropropane, 1,3-dichloropropane 1,1-dichlorobutane, 1,2-dichlorobutane, 1,3-dichlorobutane, 2,3-dichlorobutane, 2,2-dichlorobutane, 1,4-dichlorobutane, 1,1-dichloropentane, 1,2-dichloropentane, 1,3-dichloropentane, 1,4-dichloropentane, 1,5-dichloropentane, 2,3-dimethyl-1,3-dichloropentane, 1,3-dichloro-
3-methylbutane, 1,2-dichlorocyclopentane,
2,3-dichloropentane, 1,1-dichlorocyclopentane, 2,4-dichloropentane and the like, among which 1,2-dichloroethane, 1,2-dichloropropane, 1,2-dichlorobutane, 1 , 2-dichloropentane and the like having two chloro groups adjacent to the 1-position and 2-position give particularly high selectivity and are preferable. Furthermore, 1,2-dichloroethane and 1,2-dichloroethane are mainly for economic reasons.
Dichloropropane is particularly preferred.

In the method of the present invention, the method for causing the dichloroalkane compound to coexist in the reaction system is optional and not particularly limited. That is, the dichloroalkane compound may be added to the suspension of the raw material and the catalyst in the reaction system, or may be added after being adsorbed or supported on the catalyst in advance. Further, the coexistence amount of the dichloroalkane compound is 0.01 to 1 volume of the raw material 3-phenyl-1-bromopropane.
20 volumes, preferably 0.1 to 10 volumes. The selectivity of the target 3- (4-chlorophenyl) -1-bromopropane increases as the amount of the dichloroalkane compound increases in the above range, but even if it is added in excess of 20 volumes, the effect is further improved. Instead, it is economically disadvantageous. If it is less than 0.01, the effect of improving selectivity is insufficient. As the chlorinating agent used in the selective chlorination of the present invention, various kinds of sulfuryl chloride, thionyl chloride, phosgene and the like can be used, but usually chlorine alone is used.
Here, the chlorinating agent is usually used in an amount of 0.5 to 1 mole per 1 mole of the raw material 3-phenyl-1-bromopropane. The chlorinating agent may be added to the reaction system as it is, may be added after dilution with an inert gas such as nitrogen, or may be accompanied by air. This reaction may be performed at atmospheric pressure, under pressure, or under reduced pressure. The reaction temperature is a temperature at which the reaction solution normally maintains a liquid phase at atmospheric pressure or under pressure, preferably from 0 to 200 ° C, preferably from 20 ° C to the boiling point of the reaction solution, and more preferably from 40 to 140 ° C. . The reaction may be performed in a gas phase or a liquid phase, but is usually performed in a liquid phase. The reactor is not particularly limited, and may be, for example, a batch system, a semi-batch system or a continuous system, but is usually performed in a batch system.

Next, the invention (II) will be described. The present invention is as described in claims 3, 4 and 5. (B)
Is generally susceptible to the effects of trace impurities contained in the raw materials and the like, and the selectivity is generally lowered. For example, a trace amount of a halogenated phosphorus compound shows a catalytic action for side chain halogenation of an aromatic compound [J. Org. Che
m. 44, 2270 (1979)].
A trace by-product derived from the method for producing phenyl-1-bromopropane is chlorination at the benzyl position, increased ortho-chlorination,
It induces elimination of bromo group, deterioration of catalytic zeolite, etc., which is inconvenient. Surprisingly, as a result of various studies, the present inventors have found a raw material produced by a Grignard reaction of halogenobenzene and 1,3-dibromopropane, which has not been reported as a method for producing 3-phenyl-1-bromopropane. Has no negative effect on the selective chlorination reaction even when used without purification, further simplifies the process, facilitates the recovery and reuse of unreacted raw materials, and economical production The conditions of this manufacturing method with excellent advantages were established.

The halogenobenzenemagnesium, which is a Grignard reagent, is obtained by activating activated metal magnesium with an ethereal solvent such as anhydrous diethyl ether or anhydrous tetrahydrofuran in the range of 0 to 100 ° C., preferably 10 to 5 ° C.
At 0 ° C., 4-halogenobenzene was added dropwise with stirring,
It is obtained when stirring is further continued for 0.1 to 8 hours. The 4-halogenobenzene used in the present invention refers to chlorobenzene, bromobenzene and iodobenzene, all of which give the desired halogenobenzenemagnesium in high yield by this reaction, but in terms of reactivity, bromobenzene and iodobenzene are: Also, chlorobenzene is excellent in terms of economy, and can be used properly as appropriate. In the present invention,
Unreacted halogenobenzene magnesium can be reused because it produces chlorobenzene in the next chlorination step (b). The chlorobenzene separation step (4) is achieved by distilling the reaction solution obtained in the step (b). Insufficient chlorobenzene due to reaction or loss in the process is supplied from outside the process. As the metal magnesium used for the reaction, a commercially available tape-shaped or shaved (chip-shaped) metal is used, and the amount used is about 1 to 2 times the mole of halogenobenzene. In addition, prior to the reaction, stirring in a nitrogen atmosphere or under reduced pressure for the purpose of activating metal magnesium or adding a small amount of iodine or methyl iodide, ethyl bromide, dibromoethane, etc., facilitates the subsequent reaction. It is effective in proceeding to. The same results can be obtained even when the solvent used is tetrahydrofuran or diethyl ether alone or a mixture thereof with benzene or toluene.

(A) Copper compound; The copper compound used in the present invention represents a monovalent or divalent copper compound.
Inorganic salts such as copper oxide, copper fluoride, copper chloride, copper bromide, copper iodide, copper sulfate, copper carbonate and copper nitrate; organic acid salts such as copper formate, copper acetate, copper benzoate and copper octadecanoate; Copper (I) or (II) acetylacetonate, a complex compound in which carbon monoxide, nitriles, amines, phosphines, olefins, etc. are coordinated with copper; a compound in which these complex compounds are formed in the reaction system And a mixture of copper and copper. Among these copper compounds, monovalent or divalent copper chloride, copper bromide, and copper iodide are preferable, and monovalent copper chloride is particularly preferable because it gives a high yield and selectivity of the target product. The amount of the copper compound used in the reaction is not particularly limited, but is preferably in the range of 10 ^-4 to 1 in terms of molar ratio with respect to the halogenobenzene magnesium, and particularly preferably in the range of 10 ^-2 to 10 ^-1. Is preferred.

(B) Lithium compound: As the lithium compound used in the present invention, lithium oxide, lithium fluoride, lithium chloride, lithium bromide, lithium iodide,
Inorganic salts such as lithium sulfate, lithium carbonate, and lithium nitrate; lithium formate, lithium acetate, lithium benzoate,
Organic acid salts such as lithium octadecanoate can be exemplified. Among these, lithium salts are preferred, and among these lithium salts, lithium chloride, lithium bromide, and lithium iodide are preferred, and lithium chloride is particularly preferred. The amount of the lithium compound used in the reaction is not particularly limited, but may be 10 moles per mole of halogenobenzene magnesium.
^-4 to 1, preferably 10 ^-2 to 10
It is preferably in the range of ^-1 . According to the method of the present invention, both a copper compound and a lithium compound are added to the reaction system in order to allow the reaction to proceed efficiently. In this case, the molar ratio of the lithium compound to the copper compound is 0.1.
It is preferably in the range of 1 to 10, particularly preferably in the range of 1 to 5.

3-Phenyl-1-bromopropane is prepared by mixing a solvent, 1,3-dibromopropane, a copper compound and a lithium compound, and adding
The solution is added dropwise at 30 ° C. over 30 minutes to 2 hours, and the reaction solution is continued at a desired temperature and time to complete the reaction. In this case, when 1,3-dibromopropane is dropped into the Grignard reagent, the yield of 3-phenyl-1-bromopropane, which is the target substance, decreases. The amount of 1,3-dibromopropane to be used is preferably in the range of 1 to 20 in terms of molar ratio with respect to magnesium halogenobenzene, and in particular, 2 to 6
Is preferably within the range. The solvent used is 1,3
There is no restriction provided that it dissolves dibromopropane and does not interfere with the reaction. Specific examples thereof include ethers such as diethyl ether, tetrahydrofuran and dioxane, and aromatic hydrocarbons such as benzene, toluene and xylene. These solvents can be used as they are without pretreatment such as dehydration.

Although the reaction is sufficient even at 0 ° C. or less,
In order to further improve the reaction rate, the reaction is usually performed at 0 ° C. or higher. The reaction temperature is 0 to 200 ° C, preferably 20 to 15 ° C.
It is in the range of 0 ° C. The reaction is preferably carried out under an atmosphere of an inert gas such as nitrogen or argon. The reaction time depends on the reaction temperature, but is usually 0.1 to 200 hours, preferably 0.1 to 200 hours.
The range is from 5 to 50 hours. After completion of the reaction, a mineral acid such as hydrochloric acid, sulfuric acid or nitric acid or an organic acid such as acetic acid, formic acid or p-toluenesulfonic acid is added to the reaction solution to neutralize and decompose the unreacted Grignard reagent. The solvent is concentrated and removed,
The target 3-phenyl-1-bromopropane can be isolated by a general method such as extraction, distillation, crystallization, and the like. In addition, it is also possible to perform the next chlorination reaction by simply removing the solvent and without adding a purification operation.

[0018]

EXAMPLES Next, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples unless it exceeds the gist. The product was quantitatively analyzed by an internal standard method using gas chromatography to determine the conversion and selectivity. Example 1 9.76 g (0.4 mol) of chip-shaped magnesium metal and 240 mL of anhydrous tetrahydrofuran were added to a 500 mL four-necked flask purged with nitrogen, and stirred. 62.8 g (0.4 mol) of bromobenzene was dissolved in 160 mL of anhydrous tetrahydrofuran, added dropwise at 20 ° C. over 1 hour, and further stirred for 1 hour to obtain a Grignard reagent. When a part of this Grignard reagent was taken, hydrolyzed and analyzed by gas chromatography, the conversion was 99.5%. Then, the Grignard reagent obtained by the above operation is kept at 20 ° C., and the supernatant is filtered through a glass filter under a nitrogen atmosphere and transferred to another 500 mL dropping funnel in order to separate unreacted magnesium. I do. In another 1L four-necked flask,
242.4 g (1.2 mol) of 3-dibromopropane,
0.812 g (8 mmol) of copper (I) chloride, 0.684 g (12 mmol) of lithium chloride and 180 mL of tetrahydrofuran were put therein, and a Grignard reagent was added at 20 ° C.
For 1 hour. Further, the reaction solution was continuously stirred at the same temperature for 2 hours. After the reaction, the reaction solution is cooled, and
Thereafter, 1.2 g of acetic acid was added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was subjected to gas chromatography to quantitatively analyze the products. As a result, 18 mmol of unreacted benzene derived from bromobenzene, 0.34 mol of the target product, 3-phenylpropyl bromide, and 1,3- by-produced by reacting at the bromine sites at both terminals. 19.2 mmol of bisphenylpropane had been produced. The yield was 85.1% and the selectivity was 93.2%. Further, 58 g of 3-phenyl-1-bromopropane was isolated by distillation under reduced pressure (126 ° C./20 mmHg), and the yield was 72.8%.

Example 2 In a nitrogen atmosphere, 1,500 was placed in a four-neck flask having a capacity of 500 mL.
100.9 g (0.5 mol) of 3-dibromopropane,
0.202 g (2 mmol) of copper (I) chloride, 0.175 g (4 mmol) of lithium chloride and 45 mL of tetrahydrofuran were put therein, and phenylmagnesium bromide (0.1 mol) obtained by the same operation as in Example 1 was added thereto.
Of tetrahydrofuran (105 mL) was added dropwise at 20 ° C. for 1 hour. Further, the reaction solution was heated at the same temperature for 2 hours.
Stirring was continued for hours. After the reaction, the reaction solution was cooled, 0.3 g of acetic acid was added at 10 ° C. or lower, and the mixture was stirred at room temperature for 30 minutes.
As a result of quantitative analysis of the reaction product by gas chromatography, 3.5 mmol of unreacted benzene derived from bromobenzene, 91.2 mmol of the target product, 3-phenylpropyl bromide, and 1,2 produced as a by-product at the bromine sites at both terminals were obtained. 2.2 mmol of 3-bisphenylpropane had been produced. The yield was 91.2% and the selectivity was 95.4%. Further, 16.2 g of 3-phenyl-1 was obtained by distillation under reduced pressure.
-Bromopropane was isolated, and the yield was 81.3%.

Example 3 2.44 g (0.1 mol) of chip-shaped magnesium metal, 0.5 g (4.6 mmol) of ethyl bromide and 60 mL of anhydrous ethyl ether were added to a 300 mL four-necked flask purged with nitrogen and stirred. . Chlorobenzene 1
1.3 g (0.1 mol) was dissolved in 40 mL of anhydrous ethyl ether, added dropwise at room temperature over 1 hour, and further stirred at room temperature for 3 hours to obtain a Grignard reagent. When a part of this Grignard reagent was taken, hydrolyzed and analyzed by gas chromatography, the conversion was 98%. Next, in order to separate the Grignard reagent and unreacted magnesium obtained by the above operation, the supernatant is filtered through a glass filter at room temperature under a nitrogen atmosphere and transferred to another 200 mL dropping funnel. Another 50
In a 0 mL four-necked flask, 60.6 g (0.3 mol) of 1,3-dibromopropane and 0.20 g of copper (I) chloride were added.
5 g (2 mmol), lithium chloride 0.171 g (4 m
mol) and 45 mL of ethyl ether, and the Grignard reagent is added dropwise thereto at room temperature over 1 hour. Furthermore,
This reaction solution was continuously stirred at the same temperature for 2 hours. After the reaction, the reaction solution was cooled, and 0.3 g of acetic acid was added at 10 ° C. or lower to obtain 3
Stirred at room temperature for 0 minutes. As a result of quantitative analysis of the reaction solution by gas chromatography, the product was reacted at 45.1 mmol of benzene in which the Grignard reagent was hydrolyzed, 41.2 mmol of the target product 3-phenyl-1-bromopropane, and bromine at both ends. 3.1 mmol of 1,3-bisphenylpropane by-produced. Yield 4
The selectivity was 1.2% and the selectivity was 90.3%. Further, the reaction solution was filtered through a glass filter to remove magnesium halide, and then the solvent was removed under reduced pressure to obtain a crude reaction solution.

Example 4 2.44 g (0.1 mol) of chip-shaped magnesium metal and 60 mL of anhydrous ethyl ether were added to a 300 mL four-necked flask purged with nitrogen and stirred. 15.73 g (0.1 mol) of bromobenzene was dissolved in 40 mL of anhydrous ethyl ether, added dropwise at 20 ° C. over 1 hour, and further stirred for 1 hour to obtain a Grignard reagent. When a part of the Grignard reagent was taken, hydrolyzed and analyzed by gas chromatography, the conversion was 99.2%. Next, the Grignard reagent obtained by the above operation was kept at 20 ° C., and under an atmosphere of nitrogen, the supernatant was filtered through a glass filter under a nitrogen atmosphere to separate unreacted magnesium, and the filtered supernatant was placed in another 200 mL dropping funnel. Transfer. In another 500 mL four-neck flask, 60.5 g (0.3 mol) of 1,3-dibromopropane was added.
l), 0.207 g (2 mmol) of copper (I) chloride, 0.170 g (4 mmol) of lithium chloride and 45 mL of anhydrous ethyl ether were added.
Add dropwise over 1 hour at ° C. Further, the reaction solution was continuously stirred at the same temperature for 2 hours. After the reaction, the reaction solution is cooled and 10
At 0.3 ° C. or lower, 0.3 g of acetic acid was added, and the mixture was stirred at room temperature for 30 minutes. As a result of quantitative analysis of the product by gas chromatography, the reaction solution was reacted at 2.5 mmol of unreacted benzene derived from bromobenzene, 87.4 mmol of the target product, 3-phenyl-1-bromopropane, and bromine at both ends to produce by-products. 1,3-bisphenylpropane 4.4 mmol
Had been generated. The yield is 87.4% and the selectivity is 94.5.
%Met. Further, the reaction solution was filtered through a glass filter to remove magnesium bromide, and then the solvent was removed under reduced pressure to obtain a crude reaction solution.

Example 5 A 200 mL glass four-necked flask equipped with a reflux condenser, a gas injection tube and a stirring function was previously activated with KL zeolite at a temperature of 300 ° C. or higher under nitrogen flow (JGC Universal: LZ- KL) 1 g and 50 g (0.25 mol) of 3-phenyl-1-bromopropane and 50 g each of 1,2-dichloroethane obtained by the same operation as in Example 1 were charged, and stirred while flowing nitrogen and air. C. and kept for 30 minutes. Thereafter, the nitrogen was switched to chlorine gas at a flow rate of 170 mL / min and reacted for 6 hours. The reaction was carried out by shielding the entire reaction part with a metal light-shielding device so as to prevent light from entering from outside. After completion of the reaction, the reaction solution was cooled to room temperature under a nitrogen gas flow, and the catalyst zeolite was separated. The reaction solution was analyzed by gas chromatography using an internal standard method. As a result, 17.1 mmol of unreacted 3-phenyl-1-bromopropane was obtained. 3- (4-chlorophenyl) -1-bromopropane, 0.18 mol,
The conversion was 93.2%, the selectivity was 76.8%, and the p / o ratio in the product was 3.3.

Example 6 The same reaction conditions as in Example 5 except that 50 g of 1,2-dichloroethane was replaced with 50 g of 1,2-dichloropropane,
A chlorination reaction was performed by operation. After the completion of the reaction, the reaction solution was cooled to room temperature under nitrogen gas flow, and the catalyst zeolite was separated.
As a result of analysis by gas chromatography according to the internal standard method, unreacted 3-phenyl-1-bromopropane 0.1.
104 mol, target product 3- (4-chlorophenyl) -1
0.107 mol of bromopropane and a conversion of 58.
4%, selectivity 73.4%, p / o ratio in the product 3.
It was 4.

Example 7 1 g of KL zeolite (LZ-KL, manufactured by JGC Universal Co., Ltd.) used as a catalyst was changed to 3 g, and the reaction time was changed to 1.g.
A chlorination reaction was carried out under the same reaction conditions and operation as in Example 5, except that the time was changed to 5 hours. After the completion of the reaction, the reaction solution was cooled to room temperature under nitrogen gas flow, and the catalyst zeolite was separated.As a result of analysis by gas chromatography according to the internal standard method,
Unreacted 3-phenyl-1-bromopropane 12.3 m
mol, the target product, 0.194 mol of 3- (4-chlorophenyl) -1-bromopropane, and the conversion was 95.1%.
The selectivity was 81.2% and the p / o ratio in the product was 4.9.

Example 8 A chlorination reaction was carried out under the same reaction conditions and operations as in Example 5, except that 50 g of 1,2-dichloroethane was changed to 100 g and the reaction time was changed to 3 hours. After completion of the reaction, the reaction solution was cooled to room temperature under nitrogen gas flow, and the catalyst zeolite was separated. The reaction solution was analyzed by gas chromatography using an internal standard method. As a result, 13.8 mmol of unreacted 3-phenyl-1-bromopropane was obtained. Compound 3- (4-chlorophenyl)
With 0.199 mol of -1-bromopropane, the conversion was 9
The selectivity was 4.5%, the selectivity was 83.9%, and the p / o ratio in the product was 6.1.

Example 9 The procedure was carried out except that 1 g of KL zeolite (LZ-KL, JGC Universal Co., Ltd.) used as a catalyst was increased to 3 g, 50 g of 1,2-dichloroethane was increased to 100 g, and the reaction time was changed to 2 hours. A chlorination reaction was carried out under the same reaction conditions and operation as in Example 5. After the completion of the reaction, the reaction solution was cooled to room temperature under a nitrogen gas flow, and the catalyst zeolite was separated. As a result of analysis by gas chromatography according to an internal standard method, unreacted 3-phenyl-1-bromopropane (3.5 mmol) was obtained. Compound 3- (4-chlorophenyl) -1-bromopropane 0.21 mol, conversion rate 98.6%, selectivity 8
4.7%, the p / o ratio in the product was 6.3.

Example 10 1 g of KL zeolite (JGC Universal Co., Ltd .: LZ-KL) used as a catalyst was increased to 2.75 g, 50 g of 1,2-dichloropropane was increased to 100 g, and the reaction time was increased to 4 g.
A chlorination reaction was carried out under the same reaction conditions and operation as in Example 6, except for the time. After completion of the reaction, the reaction solution was cooled to room temperature under a nitrogen gas flow, and the catalyst zeolite was separated. The reaction solution was analyzed by gas chromatography using an internal standard method. As a result, unreacted 3-phenyl-1-bromopropane 11.8 mm was obtained.
ol, 0.197 mol of 3- (4-chlorophenyl) -1-bromopropane as a target product, the conversion was 95.3%, the selectivity was 82.3%, and the p / o ratio in the product was 5.3. there were.

Example 11 A 200 mL glass four-necked flask equipped with a reflux condenser, a gas injection tube and a stirring function was previously activated with KL zeolite at a temperature of 300 ° C. or higher under a nitrogen flow (JGC Universal: LZ- KL) (1.1 g) and 6.1 g (30.6 mmol) of 3-phenyl-1-bromopropane and 51 g of each of 1,2-dichloroethane obtained by the same operation as in Example 1 were charged, and nitrogen and air were passed through. With stirring, the temperature was raised to 50 ° C. and maintained for 30 minutes. Thereafter, nitrogen was switched to chlorine gas at a flow rate of 70 mL / min and reacted for 50 minutes. The reaction was carried out by shielding the entire reaction part with a metal light-shielding device so as to prevent light from entering from outside. After completion of the reaction, the reaction solution was cooled to room temperature under nitrogen gas flow, and the catalyst zeolite was separated. The reaction solution was analyzed by gas chromatography using an internal standard method.
-Bromopropane was not detected and the target product, 3- (4-chlorophenyl) -1-bromopropane, 27.8 mmol
The conversion was 100%, the selectivity was 90.9%, and the p / o ratio in the product was 10.7.

Example 12 A 50 mL glass four-necked flask equipped with a reflux condenser, a gas injection tube, and a stirring function was previously activated with KL zeolite at a temperature of 300 ° C. or higher under a nitrogen flow (JGC Universal: LZ- KL) 160 mg and the reaction solution (8.2 g of 3-phenyl-1-bromopropane) obtained in Example 3 and 8.2 each of 1,2-dichloroethane.
g, and the temperature was raised to 50 ° C. while stirring under a flow of nitrogen and air, and the temperature was maintained for 30 minutes. Thereafter, nitrogen was switched to chlorine gas at a flow rate of 30 mL / min and reacted for 6 hours. The reaction was carried out by shielding the entire reaction section from light from outside with a metal light-shielding device. After completion of the reaction, the reaction solution was cooled to room temperature under a flow of nitrogen gas to separate the catalyst zeolite, and analyzed by gas chromatography according to an internal standard method. As a result, unreacted 3-phenyl-1-bromopropane 3.2 was obtained.
mmol, the target product 3- (4-chlorophenyl) -1-bromopropane is 28.8 mmol, and the conversion is 93.2.
%, Selectivity 75.0%, p / o ratio in the product is 3.2
Met. By distilling the obtained reaction solution under normal pressure,
After collecting 8 g of 1,2-dichloroethane (bp; 83 ° C.) and 5 g of chlorobenzene (bp; 132 ° C.), 3- (4-chlorophenyl) -1 was obtained by distillation under reduced pressure.
6.2 g of bromopropane were obtained (bp; 98 ° C./0.
8 mmHg).

Example 13 A 100 mL glass four-necked flask equipped with a reflux condenser, a gas injection tube and a stirring function was previously activated with KL zeolite at a temperature of 300 ° C. or higher under a nitrogen flow (JGC Universal: LZ- KL) 350 mg and the reaction solution (3-phenyl-1-bromopropane 17.4 g) and 1,2-dichloroethane 1 obtained each in Example 4.
7.4 g was charged and stirred under nitrogen and air flow.
C. and kept for 30 minutes. Thereafter, nitrogen is added at 70 min / min.
The reaction was switched to chlorine gas at a mL flow rate for 6 hours. still,
The reaction was carried out by shielding the entire reaction part from light from outside with a metal light-shielding device. After the completion of the reaction, the reaction solution was cooled to room temperature under nitrogen gas flow, and the catalyst zeolite was separated. As a result of analysis by gas chromatography using an internal standard method, unreacted 3-phenyl-1-bromopropane (4.6 mmol) was obtained. Compound 3- (4-chlorophenyl)-
62.6 mmol of 1-bromopropane with a conversion of 9
4.9%, selectivity 75.6%, p / o ratio in the product was 3.2.

COMPARATIVE EXAMPLE 1 Under a nitrogen atmosphere, 68 g (0.4 mol) of 3- (4-chlorophenyl) -1-propanol was charged into a 200 mL four-necked flask equipped with a stirrer.
4 g (0.2 mmol) was added dropwise over 0.5 hour under ice cooling. Further, the reaction solution was continuously stirred at 100 ° C. for 1 hour. After the reaction, the reaction solution was cooled, 20 g of ice was added, and the organic layer was extracted with 120 g of pentane. After drying over anhydrous magnesium sulfate, the reaction mixture was distilled to obtain 58 g (0.29 mol).
1; bp; 75 ° C./0.1 mmHg) to give 3- (4-chlorophenyl) -1-bromopropane (yield 7).
2.8%).

Comparative Example 2 A chlorination reaction was carried out under the same reaction conditions and operations as in Example 5 except that 50 g of 1,2-dichloroethane was not added.
After completion of the reaction, the reaction solution was cooled to room temperature under a flow of nitrogen gas, and the catalyst zeolite was separated. As a result of analysis by gas chromatography according to an internal standard method, unreacted 3-phenyl-
24.4 mmol of 1-bromopropane, 3- (4
-Chlorophenyl) -1-bromopropane 0.151 m
In ol, the conversion was 90.3%, the selectivity was 66.5%, and the p / o ratio in the product was 2.3.

Comparative Example 3 The same reaction conditions as in Example 5 except that 50 g of 1,2-dichloroethane were replaced with 4.7 g of m-dinitrobenzene,
A chlorination reaction was performed by operation. After the completion of the reaction, the reaction solution was cooled to room temperature under nitrogen gas flow, and the catalyst zeolite was separated.
As a result of analysis by gas chromatography according to the internal standard method, unreacted 3-phenyl-1-bromopropane 1
3.8 mmol, the desired product 3- (4-chlorophenyl)-
0.157 mol of 1-bromopropane with a conversion of 9
4.5%, selectivity 66.1%, p / o ratio in the product was 2.4.

Comparative Example 4 A 200 mL glass four-necked flask equipped with a reflux condenser, a gas injection tube, and a stirring function was previously activated with KL zeolite at a temperature of 300 ° C. or more under a nitrogen flow (JGC Universal: LZ- KL) 1 g, 3-phenyl-1-bromopropane 50 g (0.251 mol) obtained by the same operation as in Example 1, and methylene chloride 50 each.
g was maintained at 20 ° C. while stirring under flowing nitrogen and air. Thereafter, the nitrogen was switched to chlorine gas at a flow rate of 10 mL / min and reacted for 18 hours. The reaction was carried out by shielding the entire reaction section from light from outside with a metal light-shielding device. After completion of the reaction, the reaction solution was cooled to room temperature under a flow of nitrogen gas to separate the catalyst zeolite, and analyzed by gas chromatography using an internal standard method. As a result, unreacted 3-phenyl-1-bromopropane 0.175 mol,
0.2 mmol of the desired product, 3- (4-chlorophenyl) -1-bromopropane, with a conversion of 30.3% and a selectivity of 6
6.1%, the p / o ratio in the product was 2.2.

Comparative Example 5 A 200 mL glass four-necked flask equipped with a reflux condenser, a gas injection tube, and a stirring function was previously activated with KL zeolite at 300 ° C. or higher under a nitrogen flow (Nikki Universal Co., Ltd .: LZ- KL) 50 g of 3-phenyl-1-bromopropane obtained in 1 g and Comparative Example 1
(0.251 mol) and 1,2-dichloroethane 5 each
Then, the temperature was raised to 50 ° C. while stirring under nitrogen and air flow, and the temperature was maintained for 30 minutes. After that, 170m / min of nitrogen
The gas was switched to chlorine gas at an L flow rate and reacted for 6 hours. The reaction was carried out by shielding the entire reaction section from light from outside with a metal light-shielding device. After completion of the reaction, the reaction solution was cooled to room temperature under nitrogen gas flow, and the catalyst zeolite was separated. The reaction solution was analyzed by gas chromatography using an internal standard method. As a result, 38.9 mol of unreacted 3-phenyl-1-bromopropane was obtained. Compound 3- (4-chlorophenyl)-
0.144 mol of 1-bromopropane and a conversion of 8
The selectivity was 4.5%, the selectivity was 67.6%, and the p / o ratio in the product was 2.6.

[0036]

According to the production method of the present invention, 3- (4-chlorophenyl)-useful as an intermediate for medicines and agricultural chemicals.
1-bromopropane in high yield, high selectivity and safely,
Moreover, since it can be obtained by a simple operation, it is industrially extremely advantageous.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 25/02 C07C 25/02 // C07B 61/00 300 C07B 61/00 300 (72) Inventor Shuji Ichikawa Mitsubishi Chemical Co., Ltd. Tsukuba Research Laboratory F-term (reference) 4H006 AA02 AC24 AC30 BA03 BA05 BA49 BA71 BB12 BD70 BE51 BE52 BE53 EA21 4H039 CA41 CA52 CD10 CD20

Claims (5)

[Claims] 1. A method for producing 3- (4-chlorophenyl) -1-bromopropane, which comprises chlorinating 3-phenyl-1-bromopropane in a paraselective manner using a zeolite catalyst in the presence of dichloroalkane. Production method. 2. The method for producing 3- (4-chlorophenyl) -1-bromopropane according to claim 1, wherein the zeolite is an L-type zeolite. 3. A method comprising: (a) subjecting magnesium halogenobenzene and 1,3-dibromopropane to a Grignard reaction;
(B) Then, the obtained 3-phenyl-1-bromopropane is chlorinated in a para-selective manner using a zeolite catalyst in the presence of dichloroalkane. A method for producing 3- (4-chlorophenyl) -1-bromopropane. 4. The method according to claim 3, wherein chlorobenzene by-produced in the step (b) is separated and used in the step (a).
3. The method for producing 3- (4-chlorophenyl) -1-bromopropane described in 1. above. 5. The method for producing 3- (4-chlorophenyl) -1-bromopropane according to claim 3, wherein the reaction in the step (a) is performed in the presence of a copper compound and a lithium compound. .