JP2000256298A - Production of aromatic alpha-bromoalkyl compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method by which an aromatic α-bromoalkyl compound can efficiently be produced from an aromatic alkyl compound without using an expensive brominating agent. SOLUTION: This method is to brominate an aromatic alkyl compound in an organic solvent with bromine. The aromatic alkyl compound is dissolved in the organic solvent and a radical initiator and bromine are added to the resultant solution of the aromatic alkyl compound in the organic solvent while aerating an inert gas thereinto. The radical initiator is preferably dividedly or continuously added to the solution of the aromatic alkyl compound in the organic solvent so that the radical initiator is always present in the solution of the aromatic alkyl compound in the organic solvent until the bromination of the aromatic alkyl compound is completed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing an aromatic α-bromoalkyl compound. For more information,
Aromatic α useful as a synthetic intermediate for fine chemicals and pharmaceuticals
A method for producing a bromoalkyl compound.

[0002]

2. Description of the Related Art Generally, as a method for brominating an aromatic alkyl compound, an α-bromination method using bromine is known. However, when this method is carried out on a small experimental scale, the reaction may proceed, but when it is carried out on a factory scale, hydrogen bromide accumulates in the reaction system, and bromination stops. However, there is a disadvantage of being delayed.

[0003] In recent years, as a method of brominating an aromatic alkyl compound without using bromine, 4'-methyl-2-cyanobiphenyl, which is an aromatic alkyl compound, is converted to N-bromosuccinimide, which is a brominating agent. A method for brominating is known (JP-A-6-192170).

However, since the N-bromosuccinimide used in this method is expensive, the aromatic alkyl compound is efficiently brominated without using an expensive brominating agent such as N-bromosuccinimide. The development of a method that can do this is awaited.

[0005]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above prior art, and is intended to efficiently convert an aromatic α-bromoalkyl compound from an aromatic alkyl compound without using an expensive brominating agent. An object is to provide a method that can be manufactured well.

[0006]

That is, the present invention relates to a method for brominating an aromatic alkyl compound with bromine in an organic solvent, wherein the aromatic alkyl compound is dissolved in the organic solvent to obtain an aromatic compound. The present invention relates to a method for producing an aromatic α-bromoalkyl compound, which comprises adding a radical initiator and bromine while passing an inert gas through an organic solvent solution of an alkyl compound.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The method for producing an aromatic α-bromoalkyl compound according to the present invention comprises dissolving an aromatic alkyl compound in an organic solvent, The method is characterized in that a radical initiator and bromine are added while an inert gas is passed through the device.

[0008] The aromatic alkyl compound means a compound in which a hydrogen atom of an aromatic compound is an alkyl group. Here, as the alkyl group, a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group,
Examples thereof include an i-butyl group, and among them, a methyl group is preferable. Examples of the aromatic compound include, for example, benzene, condensed rings such as naphthalene and anthracene, and alkyl-substituted heterocyclic compounds such as pyridine and quinoline.

The aromatic alkyl compound may have a substituent such as a nitro group, a halogen atom, a cyano group, a carboxyl group and an alkoxycarbonyl group. As a typical example of the aromatic alkyl compound, 4′-methyl-
2-cyanobiphenyl is mentioned. When 4'-methyl-2-cyanobiphenyl is used as the aromatic alkyl compound, 4'-bromomethyl-2-cyanobiphenyl is obtained as the aromatic α-bromoalkyl compound as the target compound.

From the viewpoint of efficient bromination, the organic solvent is preferably an organic solvent that is difficult to be brominated. Examples of organic solvents that are difficult to be brominated include, for example,
Halogenated aromatic hydrocarbons such as chlorobenzene, o-dichlorobenzene and bromobenzene, saturated aliphatic hydrocarbons having 5 to 7 carbon atoms such as hexane and heptane, and saturated halogenated hydrocarbons having 1 to 6 carbon atoms such as methylene chloride and dichloroethylene 6 carbon atoms such as aliphatic hydrocarbons and cyclohexane
To 8 alicyclic hydrocarbons, and these can be used alone or in combination of two or more. Among these, halogenated aromatic hydrocarbons and halogenated saturated aliphatic hydrocarbons having 1 to 6 carbon atoms, in particular,
Chlorobenzene and dichloroethylene can be suitably used in the present invention.

The amount of the organic solvent used is preferably at least 100 parts by weight, more preferably at least 300 parts by weight, from the viewpoint of efficient bromination with respect to 100 parts by weight of the aromatic alkyl compound. From the viewpoint of avoiding a decrease in industrial productivity due to an increase in the reaction solution, and not more than 1500 parts by weight, preferably 100 parts by weight.
It is desirable that the content be 0 parts by weight or less.

An organic solvent solution of an aromatic alkyl compound obtained by dissolving an aromatic alkyl compound in an organic solvent,
Vent inert gas.

As the inert gas, for example, nitrogen gas,
Examples include argon gas and helium gas. Among them, nitrogen gas can be suitably used in the present invention because it is inexpensive.

The flow rate of the inert gas when the inert gas is passed through the organic solvent solution is such that hydrogen bromide generated when the aromatic alkyl compound is brominated is efficiently removed from the organic solvent solution, From the viewpoint of promoting the conversion, per mole of the aromatic alkyl compound, 10 ml / min or more,
Preferably, it is 50 ml / min or more, and if used in an excessively large amount, the effect corresponding to it is not exhibited, which is rather uneconomical.
00 ml / min or less, preferably 500 ml / min
It is desirable to make the following. When the inert gas is passed, the inert gas is introduced into the organic solvent solution from the viewpoint of improving the dispersibility of the inert gas and more efficiently discharging hydrogen bromide from the organic solvent solution. In this case, it is preferable that the diameter of the vent hole at the distal end of the introduction pipe used is reduced, the number of holes is increased, and the inert gas is ventilated from the bottom of the organic solvent solution as much as possible. Also,
From the viewpoint of increasing the bromination efficiency, it is preferable to continuously perform the ventilation of the inert gas until the end of the bromination.

A radical initiator and bromine are added while passing an inert gas through the organic solvent solution.

As the radical initiator, for example, 2,
2'-azobis-2-methylbutyronitrile, 1,1 '
Azobis-1-cyclohexanecarbonitrile, 2,
2'-azobis-2-isobutyronitrile, benzoyl peroxide and the like can be mentioned, and these can be used alone or in combination of two or more. Among these, 2,2′-azobis-2-methylbutyronitrile and 1,1′-azobis-1-cyclohexanecarbonitrile are difficult to dissolve in the organic solvent used for the bromination reaction and the radical thereof. From the viewpoint of excellent stability, it can be suitably used in the present invention.

From the viewpoint of accelerating bromination per mole of the aromatic alkyl compound,
0.0001 mol or more, preferably 0.005 mol or more.
From the viewpoint of avoiding coloring of the -bromoalkyl compound and improving the economic efficiency, it is desirable that the amount be 0.1 mol or less, preferably 0.05 mol or less.

When the radical initiator is added to the organic solvent solution, a solution in which the radical initiator is dissolved in the organic solvent is prepared in advance, and the solution is added to the organic solvent solution. It is preferable from the viewpoint of preventing contamination of the working environment and improving industrial productivity. in this case,
The amount of the organic solvent is, per 100 parts by weight of the radical initiator,
About 300 to 1500 parts by weight, preferably 500 to 80 parts by weight
It is desirably about 0 parts by weight.

In addition, when the radical initiator is added to the organic solvent solution, the radical initiator is not added to the organic solvent solution at the beginning of the bromination, but the bromination of the aromatic alkyl compound is performed. It is preferable to add the radical initiator in portions or continuously so that the radical initiator is always present in the organic solvent solution until the above is completed. This is because, when the radical initiator is added to the organic solvent solution at the same time at the start of bromination, the radical initiator is decomposed during the bromination, and the reaction is delayed or stopped. Therefore, when the radical initiator is dividedly or continuously added to the organic solvent solution, for example, about 10 to 50% by weight of the total used amount of the radical initiator is added at the start of bromination, and Is preferably added in portions or continuously so that the radical initiator is always present in the organic solvent solution until the bromination is completed.

When adding bromine to an organic solvent solution,
Rather than adding bromine all at once in the early stage of bromination, the bromine is divided or continuously so that bromine is always present in the organic solvent solution until bromination of the aromatic alkyl compound is completed. It is preferred to add. When bromine is added to the organic solvent solution at once at the start of bromination,
This is because dibromination, which is a side reaction, easily occurs, and the selectivity decreases. Therefore, when bromine is dividedly or continuously added to the organic solvent solution, for example, about 1 to 5% by weight of the total use amount of bromine is added at the start of bromination, and the remaining amount is reduced by bromination. It is preferred that bromine be added in portions or continuously so that bromine is always present in the organic solvent solution until completion. The bromine may be added simultaneously with the radical initiator, or may be added separately from the radical initiator.

The temperature of the solution of the organic solvent at the time of bromination is preferably 0 ° C. or higher, preferably 40 ° C. or higher, from the viewpoint of prompt bromination, and the selectivity of the bromination reaction is low. From the viewpoint of preventing the decrease and eliminating the formation of dibromo bodies and the residual aromatic alkyl compounds, 110 ° C or lower,
Preferably, the temperature is 90 ° C. or lower.

The time required for bromination depends on the type of the aromatic alkyl compound, the type of the radical initiator, the reaction temperature and the like, but is usually about 3 to 12 hours, preferably about 5 to 12 hours.
About 10 hours.

The completion of the bromination can be confirmed by the fact that the coloring by the bromine has disappeared.

The aromatic α-bromoalkyl compound obtained after the completion of the bromination can be isolated from the reaction mixture, if necessary. Examples of the isolation method include, for example, a method of distilling a solvent from a reaction mixture, followed by crystallization with an appropriate solvent, a method of distillation, and the like, but the present invention is not limited to only such a method. . When the reaction mixture is used as it is in the next step, it is needless to say that it need not be isolated from the reaction mixture.

[0025]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to only these examples.

Example 1 102 g of 4'-methyl-2-cyanobiphenyl was dissolved in 303 g of monochlorobenzene and heated to 60.degree.
To this solution, about 25% by weight of a monochlorobenzene solution in which 4.17 g of 2,2′-azobis-2-methylbutyronitrile was dissolved in 30.6 g of monochlorobenzene.
Was added.

Next, nitrogen gas was added to the solution at a flow rate of 70 ml.
While maintaining the liquid temperature at 60 to 65 ° C. while blowing at a rate of about 75% by weight of the remaining amount of the monochlorobenzene solution.
At the same time, 89.3 g of bromine was added dropwise over about 7 hours to perform bromination.

After completion of the bromination, the resulting reaction mixture was analyzed by high performance liquid chromatography to find that the composition was 45.9% of the desired product, 4′-bromomethyl-2-cyanobiphenyl, and 4 ′ as the starting material. -Methyl-2-
8.9% of cyanobiphenyl and 5.2% of 4 ', 4'-dibromomethyl-2-cyanobiphenyl.

Next, about 80% of monochlorobenzene was obtained under reduced pressure.
g was distilled off, the mixture was concentrated, and cooled to -10 ° C to precipitate crystals. The precipitated crystals were filtered, washed with n-heptane, and dried to obtain 4'-bromomethyl-2-cyanobiphenyl.

The yield of the obtained 4'-bromomethyl-2-cyanobiphenyl was 96.6 g (yield: 6
7.2%).

Example 2 102 g of 4'-methyl-2-cyanobiphenyl was dissolved in 303 g of monochlorobenzene and heated to 80.degree.
To this solution, 5.08 g of 1,1′-azobis-1-cyclohexanecarbonitrile was added to 30.30% of monochlorobenzene.
About 2 of the monochlorobenzene solution dissolved in 6 g
5% by weight was added.

Next, nitrogen gas was added to the solution at a flow rate of 50 ml.
/ Min while maintaining the liquid temperature at 80 ° C.
89.3 g of bromine together with the remaining amount of about 75% by weight of the monochlorobenzene solution was added dropwise over about 7 hours to perform bromination.

After completion of the bromination, about 80 g of monochlorobenzene was distilled off under reduced pressure, concentrated, and cooled to -10 ° C. to crystallize crystals. The precipitated crystals were filtered, washed with n-heptane, and dried to obtain 4'-bromomethyl-2-cyanobiphenyl.

The yield of the obtained 4'-bromomethyl-2-cyanobiphenyl was 96.2 g (yield: 6
7.0%).

Example 3 After dissolving 102 g of 4'-methyl-2-cyanobiphenyl in 303 g of monochlorobenzene,
Crystal powder of 2'-azobisisobutyronitrile 0.87
g and warmed to about 60 ° C.

Next, while blowing nitrogen gas into the solution, 89.3 g of bromine was added dropwise over about 7 hours to perform bromination. During the dropping of bromine, 2.68 g of crystal powder of 2,2′-azobisisobutyronitrile was added in seven portions.

After completion of the bromination, the resulting reaction mixture was analyzed by high performance liquid chromatography to find that the composition was 74.8% of the desired product, 4'-bromomethyl-2-cyanobiphenyl, and 4 'as the starting material. -Methyl-2-
12.7% of cyanobiphenyl and 8.1% of 4 ', 4'-dibromomethyl-2-cyanobiphenyl.

Next, about 80% of monochlorobenzene was obtained under reduced pressure.
g was distilled off, the mixture was concentrated, and cooled to -10 ° C to precipitate crystals. The precipitated crystals were filtered, washed with n-heptane, and dried to obtain 4'-bromomethyl-2-cyanobiphenyl.

The yield of the obtained 4'-bromomethyl-2-cyanobiphenyl was 96.6 g (yield: 6
7.2%).

Comparative Example 1 102 g of 4'-methyl-2-cyanobiphenyl was dissolved in 303 g of monochlorobenzene and heated to 60.degree.
To this solution, about 25% by weight of a monochlorobenzene solution in which 4.17 g of 2,2′-azobis-2-methylbutyronitrile was dissolved in 30.6 g of monochlorobenzene.
Was added.

Next, while maintaining the liquid temperature at 60 to 65 ° C., 89.3 g of bromine was added dropwise together with the remaining amount of about 75% by weight of the monochlorobenzene solution, and bromination was carried out. After a time, coloring with bromine was observed, and bromination was delayed.

7 hours after the start of the bromination, a monochlorobenzene solution obtained by further dissolving 89.3 g of bromine and 4.17 g of 2,2'-azobis-2-methylbutyronitrile in 30.6 g of monochlorobenzene. 77 g was added dropwise, and 41% of the starting material, 4'-methyl-2-cyanobiphenyl, remained.

Therefore, 2,2′-
After a monochlorobenzene solution obtained by dissolving 2.2 g of azobis-2-methylbutyronitrile in 20 g of monochlorobenzene and 22 g of bromine were added dropwise over 4 hours, the resulting reaction mixture was analyzed by high performance liquid chromatography. 4'-bromomethyl-2
-Cyanobiphenyl 66.3%, starting material 4'-
18.5% of methyl-2-cyanobiphenyl and 4,
4'-dibromomethyl-2-cyanobiphenyl 8.7%
Met.

Next, about 90% of monochlorobenzene was obtained under reduced pressure.
g was distilled off, the mixture was concentrated, and cooled to -10 ° C to precipitate crystals. The precipitated crystals were filtered, washed with n-heptane, and dried to obtain 4'-bromomethyl-2-cyanobiphenyl.

The yield of the obtained 4'-bromomethyl-2-cyanobiphenyl was 85.2 g (yield: 5
9.3%).

From the above results, according to the method of the embodiment,
Unlike the method of the comparative example, while passing an inert gas,
Since the radical initiator is added so that the radical initiator is always present, it can be seen that the aromatic α-bromoalkyl compound can be obtained very efficiently.

[0047]

According to the production method of the present invention, since relatively inexpensive bromine is used without using an expensive brominating agent, not only is economic efficiency excellent, but also aromatic α-bromo The effect that an alkyl compound can be manufactured efficiently is produced.

 ──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Yasuhiro Shiidahara 6-4-1, Koshimadaguchi, Kurashiki-shi, Okayama Prefecture Sumika Finechem Co., Ltd. Okayama Plant Environmental Engineering Department (72) Inventor Takuya Mashita Kojima, Kurashiki-shi, Okayama Prefecture 6-4-1, Tanoguchi Sumika Finechem Co., Ltd. Okayama Plant Environmental Technology Department F-term (reference) 4H006 AA02 AC30 BA50 BA51 BA93 BB11 BB12 BB61 BC10 BC19 BC35 BE53 BM10 BM73 FE71 FE76 QN30

Claims (7)

[Claims] 1. A method for brominating an aromatic alkyl compound with bromine in an organic solvent, comprising dissolving the aromatic alkyl compound in the organic solvent and inactivating the resulting aromatic alkyl compound in an organic solvent solution. Aromatic α-characterized by adding a radical initiator and bromine while ventilating gas.
A method for producing a bromoalkyl compound. 2. The method according to claim 1, wherein the radical initiator is divided or continuously divided so that the radical initiator is always present in the organic solvent solution of the aromatic alkyl compound until the bromination of the aromatic alkyl compound is completed. The method for producing an aromatic α-bromoalkyl compound according to claim 1, which is added to a solvent solution. 3. The method for producing an aromatic α-bromoalkyl compound according to claim 1, wherein bromine is gradually added to the organic solvent solution. 4. The method according to claim 1, wherein the aromatic alkyl compound is 4′-methyl-
The method for producing an aromatic α-bromoalkyl compound according to any one of claims 1 to 3, wherein the aromatic α-bromoalkyl compound is 2-cyanobiphenyl and the aromatic α-bromoalkyl compound is 4′-bromomethyl-2-cyanobiphenyl. 5. The method according to claim 1, wherein the radical initiator is 2,2′-azobis-
2-methylbutyronitrile or 1,1'-azobis-
5. 1-4. It is 1-cyclohexanecarbonitrile.
The method for producing an aromatic α-bromoalkyl compound according to any one of the above. 6. The method according to claim 1, wherein the inert gas is nitrogen gas.
5. The method for producing an aromatic α-bromoalkyl compound according to any one of 5. 7. The method for producing an aromatic α-bromoalkyl compound according to claim 1, wherein the organic solvent is a halogenated aromatic hydrocarbon or a halogenated saturated aliphatic hydrocarbon having 1 to 6 carbon atoms. .