JPS5949217B2 - Method for producing substituted diphenyl ether - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing substituted diphenyl ethers that are used in a wide range of fields such as agricultural chemicals, medicines, and functional polymer materials.

In general, a well-known method for producing substituted diphenyl ethers is a reaction between an alkali metal salt of a substituted phenol and a substituted halogenated benzene. However, when carrying out the above reaction, the following problems arise due to the low reactivity of the alkali metal salt of substituted phenol and substituted halogenated benzene.
That is, in order to obtain a substituted diphenyl ether in a desired yield, it is necessary to heat a mixture of a substituted phenol with an alkali metal salt and a substituted halogenated benzene at a high temperature of 200'C or higher for a long period of time.

Not only does it consume a lot of heat, but there are also restrictions on the heating method, and since the reaction takes place at high temperatures and for a long time, side reactions are likely to occur, resulting in significant product deterioration and coloring. Such products do not satisfy the purity and quality that have been strongly demanded in recent years in the fields of medicine, functional polymer materials, etc., and the fundamental calorific value of the manufacturing method is required. For this reason, various methods for producing substituted diphenyl ethers at low temperatures and in a short time with high yields have been investigated, but no satisfactory results have been obtained to date.

In the reaction between an alkali metal salt of a substituted phenol and a substituted halogenated benzene, attempts have been made, for example, to coexist with copper powder as a reaction catalyst, or to use highly polar dimethylformamide, dimethyl sulfoxide, etc. as a reaction solvent. It was difficult to significantly lower the reaction temperature.

In addition, among the alkali metal salts of substituted phenols, potassium salts, which have relatively high reactivity, were used to slightly increase the reaction rate, but this did not improve the conventional conditions, and furthermore, The drawback was that the manufacturing cost was significantly higher than that of standard atrium salt. The inventors
As a result of intensive research into a method for safely producing high-quality substituted diphenyl ether at relatively low temperatures and in a short period of time without the above disadvantages, we found that substituted ditrobenzene was prepared in a suitable organic solvent. The inventors have discovered that the above object can be easily achieved by carrying out the reaction in the presence of an alkali metal salt or an alkali metal hydroxide, and have completed the present invention.

That is, the present invention is based on the general formula (1) (wherein, X represents a nitro group or a cyano group, and n is an integer of 1 or 2).

However, when n is 2, X may be the same or different.
) is used directly, or the substituted ditrobenzene represented by formula (1) produced in the reaction system is used without isolation, and the alkali metal is dissolved in a polar organic solvent. This is a method for producing a substituted diphenyl ether represented by the general formula (2) (the symbols in the formula have the same meanings as in formula (1)) in the presence of a salt or an alkali metal hydroxide.

The present inventors continued to investigate methods for synthesizing substituted phenols at low temperatures and in a short time with good yields, but surprisingly, they found that substituted diphenols were synthesized from substituted diphenols, which had not been previously known. It has been found that enyl ether can be produced under relatively mild conditions and in good yield.

This is a novel production method that cannot be predicted even by those with sufficient knowledge in the field, and it proceeds at a much lower temperature and with better yield than the reaction of substituted phenol salts and substituted halogenated benzenes. For example, in the case of a condensation reaction between p-nitrophenol sodium salt and p-nitrochlorobenzene, the reaction usually does not proceed with a practical yield unless it is above 230°C, but the method of the present invention can produce p-dinitrobenzene. If used, it is possible to increase yields higher than conventional methods in the temperature range of 60 to 160°C. Since the reaction temperature is thus low, there are few undesirable side reaction products, and furthermore, there is little coloring of the obtained target product, and a highly pure product can be easily obtained. Furthermore, a significant feature of the process of the present invention is that it does not require two aromatic compounds as starting materials, as in conventional condensation reactions, and only substituted nitrobenzene is sufficient.

Furthermore, substituted nitrobenzene is preferable as a starting material because it can be obtained relatively inexpensively by nitration of substituted benzene, which is an industrially easy reaction. In the method of the present invention, since the reaction temperature is relatively low, various polar organic solvents can be easily used, which further speeds up the reaction.

Conventional methods using substituted phenol salts and substituted halogenated benzenes as raw materials are not advantageous because the reaction temperature is high even when a solvent is used, resulting in a pressurized reaction and requiring more expensive equipment than normal pressure reactions. When carrying out the method of the present invention, the objective can be achieved with quite simple operations.

That is, it is sufficient to simply dissolve the substituted nitrobenzene or the reaction mixture containing the substituted nitrobenzene in a polar organic solvent, further add an alkali metal salt or alkali metal hydroxide, and allow the reaction to occur at a predetermined temperature for a predetermined time. Raw material components, solvents,
There are no restrictions on the order of use or addition method of the alkali metal compounds. Furthermore, since the product can be easily separated and purified, the method of the present invention is a novel and industrially superior method. In the substituted nitrobenzene used in the method of the present invention, X in formula (1) is a nitro group or a cyano group, and the number of these groups in the molecule is 1 or 2, and 2 In this case, X may be the same or different.

Representative examples of substituted nitrobenzenes included in this range include p-cyanonitrobenzene, o-cyanonitrobenzene, m-cyanonitrobenzene, 2,4-dicyanonitrobenzene, 2,5-dicyanonitrobenzene,
Examples include 2,4-dinitro-5-cyanobenzene, p-dinitrobenzene, o-dinitrobenzene, and m-dinitrobenzene. There are no particular restrictions on the alkali metal salts or alkali metal hydroxides used in the method of the present invention, but examples of compounds that yield favorable results include sodium carbonate, acidic sodium carbonate, potassium carbonate, acidic potassium carbonate, Lithium, rubidium carbonate, cesium carbonate, sodium nitrate, potassium nitrate, lithium nitrate, rubidium nitrate, cesium nitrate, sodium nitrite, potassium nitrite, lithium nitrite; cesium nitrite, sodium phosphate, potassium phosphate, lithium phosphate, phosphorus Rubidium acid, sodium sulfate, potassium sulfate, lithium sulfate, rubidium sulfate, cesium sulfate, sodium hydroxide, potassium hydroxide, lithium hydroxide, rubidium hydroxide, cesium hydroxide, sodium formate, sodium acetate, sodium benzoate, disodium oxalate , sodium formate, potassium acetate, and the like.

There is no particular restriction on the amount of the alkali metal salt or alkali metal hydroxide used, but it may be in the range of 0.1 to 10 equivalents per mole of substituted nitrobenzene as a raw material.

More preferably, per mole of substituted nitrobenzene,
It is in the range of 0.3 to 5 equivalents. Further, the alkali metal salt used may be a hydrated salt or an anhydride, and furthermore, various organic solvents and organic compounds inert to the reaction may be included in the crystal. The alkali hydroxide used may be anhydrous or hydrated, and may also contain carbonate. Furthermore, although one type of alkali metal salt or alkali metal hydroxide may be used, good results can be obtained by using two or more types of compounds.

For example, there are mixtures of two types, such as sodium carbonate and potassium carbonate, and sodium carbonate and potassium hydroxide, as well as mixtures of three or more types, and similarly good results can be obtained. In particular, if a certain metal salt or hydroxide has excellent solubility or reactivity but is expensive, it becomes necessary to use a mixture to replace some of it with a cheaper salt. . Particularly effective solvents used in the method of the present invention are polar organic solvents, and in particular, those commonly referred to as polar aprotic solvents show excellent results. Representative examples include N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, N-methyl-2-pyrrolidone, hexamethylphosphoramide, sulfolane, and the like.
Furthermore, basic solvents such as pyridine and triethylamine, ethers such as dioxane and tetrahydrofuran,
Cellosolves such as butyl cellosolp and (enal) cellosolp can also be used, but solvents with low boiling points must be used in a closed container, which imposes significant restrictions on their use. There is no particular restriction on the amount of solvent used, but it varies widely depending on not only the type of solvent but also the type of substituted nitrobenzene used as a raw material.

Generally, from 0.3 to the weight of the substituted nitrobenzene used.
Use 50 times the amount of solvent, preferably 0.5 to 30
Use solvents in the range of Further, the solvent may be anhydrous or hydrated.

In the case of a water-containing solvent, even if the solvent contains water in an amount not exceeding 30%, the reaction will not be hindered, and in some cases, it may show better results than an anhydrous solvent. This is because the solubility of the alkali metal salt or alkali metal hydroxide present in the reaction system in the solvent is significantly increased by the presence of water, and the reaction is promoted. However, when the water content in the solvent exceeds 30%, the solubility of the substituted nitrobenzene as a raw material decreases rapidly, and the yield of the desired product, the substituted diphenyl ether, decreases rapidly. In carrying out the method of the present invention, the reaction temperature varies depending on the type of substituted nitrobenzene used, the type of alkali metal salt or hydroxide, and the type of solvent, but is usually 60-200 m
It is carried out within the range of °C. Below 60'C, the reaction rate of substituted nitrobenzene accumulates and is low, making it impractical, and when 200 is above C, substituted nitrobenzene becomes unstable.
This not only accelerates side reactions, but also causes the reaction to proceed explosively, making it unsuitable as a condition for actual implementation.

A particularly preferred temperature range is 100-180°C.
Further, the reaction time is greatly influenced by the reaction temperature, the type of reaction raw materials, etc., but is preferably in the range of 30 minutes to 30 hours.

If the reaction is continued at a relatively high temperature for a long time, the produced substituted diphenyl ethers may decompose or re-react, resulting in a decrease in the yield of the target product. There are no particular restrictions on the reaction method when carrying out the method of the present invention.

In particular, the method and order of addition of reaction components and solvents are not limited, and various methods can be employed depending on the purpose. Although a stirring device is usually used in the reaction, the method of the present invention can also be carried out without stirring. Further, as a matter of course, there are no restrictions on the shape, material, heating method, temperature control method, etc. of the reactor, and the reaction can be carried out at either pressurized or normal pressure. In addition, good results may be obtained by replacing the inside of the reactor with an inert gas or other specific gas, or by conducting the reaction in a stream of such gas or under pressure.

Nitrogen, argon, helium, etc. are used as inert gases, and examples of other specific gases include nitrogen dioxide, nitrogen monoxide, dinitrogen trioxide, and various other gases are used. be done. Partitioning of the substituted diphenyl ether produced by the method of the present invention is easy and can be carried out in a short time and by simple operations.

Since the substituted diphenyl ether produced is usually dissolved in a solvent, a common method is to add a precipitant such as water or methanol to precipitate, and then separate and dry the precipitate. However, if the solvent used has a relatively low boiling point, the target product can also be recovered by distilling off the solvent and washing the residue. Furthermore, depending on the type of solvent, most crystals of the desired substituted diphenyl ether may be analyzed simply by cooling the reaction solution to room temperature, so it may be necessary to simply separate, wash, and dry the crystals. , the target product with high purity can be obtained. If the target product is a liquid, it is common to purify it by distillation after distilling off the solvent, but it is also possible to add water etc. to the reaction solution to separate the two layers and separate them by liquid separation. . Hereinafter, the method of the present invention will be explained in more detail in Examples.

Example 1 33.69 (0.2
mol) and sodium carbonate 10.69 (0.1 mol)
Weigh out and add 80f of dimethyl sulfoxide! was added and stirred at room temperature for 30 minutes.

The mixture was further heated to 135°C over 35 minutes with stirring, and the mixture was reacted with stirring at 135°C for an additional 2 hours, after which heating was stopped and the mixture was allowed to cool at room temperature. After cooling, 200 ml of water was added to the reaction solution, and a pale yellow solid precipitated. After being left for 30 minutes, it was separated and dried.

This pale yellow solid exhibits a melting point of 139-14FC and an IR
This revealed that it was 4,4'-dinitrodiphenyl ether. 80ml of toluene was added to the above pale yellow solid.
was dissolved at 80'C, allowed to cool to room temperature, and recrystallized. As a result, 23.7g (
Yield: 91%). Examples 2 to 8 The same procedure as in Example 1 was performed except that other alkali metal salts or alkali metal hydroxides were used in place of sodium carbonate in Example 1, and the results shown in Table 1 were obtained.

Examples 9 to 15 Table 2 was used instead of dimethyl sulfoxide in Example 1.
The same procedure as in Example 1 was carried out except that the solvent shown in Table 2 was used, and the results shown in Table 2 were obtained.

Example 16 In a flask, 31.59 p-nitrochlorobenzene (
0.2 mol) and sodium nitrite 13.81 (
DMSOlOO containing 10% water.
y was added and stirred at room temperature for 15 minutes.

While stirring, the temperature was raised to 130'C over 30 minutes, and after further stirring for 30 minutes, a portion of the reaction solution was collected.
Gas chromatography (column M-IezOneCr)
As a result of analysis at easeL (3 mm length, 3 m column temperature, 150° C.), it was revealed that the concentration of p-nitrochlorobenzene was significantly reduced, and p-dinitrobenzene was produced.

Without separating the generated p-dinitrobenzene, 10.69 (0.1 mol) of sodium carbonate was further added, and the reaction was stirred at 135°C for 4 hours. The reaction solution was collected and analyzed using gas chromatography (column Tnax).
G.C. 3mm (l), 1m, 270'C from 120°C
As a result, p-dinitrobenzene almost disappeared and only the peak of 4,4/-dinitro diphenyl ether was observed. The product was separated from the reaction solution in the same manner as in Example 1, and recrystallized from toluene to give pale yellow crystals with a melting point of 142-143°C at 24.29°C.
(yield 93%).

It was confirmed from the melting point IR and elemental analysis that it was 4,4'-dinitrodiphenyl ether. Elemental analysis results C
OC55.35H3.22NlO. 9lC6H8N2O
5 and C55.39H3. lONIO. Theoretical value (total) of 77 Example 17 The amount of sodium nitrite used in Example 16 was reduced to 6.9
The reaction was carried out using the same raw material composition as in Example 16, except that the amount was changed to 1 (0.1 mol).

After reacting at 135°C for 6 hours, the product was separated and purified in the same manner as in Example 1. As a result, pale yellow crystals with a melting point of 142-143°C corresponding to 4,4'-dinitrodiphenyl ether were obtained at 22.5°C. 9y (yield 8870) was obtained. Example
18 The reaction was carried out in the same manner as in Example 16, except that 10.61 (0.1 mol) of sodium carbonate was weighed into the reactor together with p-nitrochlorobenzene and sodium nitrite from the beginning.
After separation and purification, 23.61 pale yellow crystals with a melting point of 142-143°C corresponding to 4,4'-dinitrodiphenyl ether were obtained (yield: 9170).

Example 19 29.6 g (0.2 mol) of p-cyanonitrobenzene
and 10.69 (0.1 mol) of sodium carbonate were weighed into a reactor, 80 g of N-methyl 2-pyrrolidone was added, and the mixture was stirred at room temperature for 30 minutes and then heated to 190'C over 45 minutes.

The reaction was allowed to continue for 4 hours at 190'C with stirring, and after completion of the reaction, the reaction was allowed to cool to room temperature. After adding 1 t of water to precipitate the reaction product, it was separated in a furnace, further washed with 300 cc of water, and then dried. Furthermore, after dissolving in 150ml of toluene and concentrating the toluene solution, it was left to stand at room temperature to obtain 15.3y of pale yellow crystals with a melting point of 175-176°C (yield 6).
9.570) obtained. The obtained crystals were confirmed to be 4,4'-dicyanodiphenyl ether from the melting point 1R, NMR and elemental analysis.

Elemental analysis results (to) C76.4lH3.5ONl2.8
9C,,H8N,O C76.35H3.66Nl2
．． 72 Theoretical value CO Examples 20 to 23: Instead of sodium carbonate in Example 1, Table 13
The results shown in Table 3 were obtained by carrying out the same procedure as in Example except that the alkali metal salt shown in Table 3 was used.

Claims (1)

[Claims] 1. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (in the formula,
represents a nitro group or a cyano group, and n is an integer of 1 or 2. However, when n is 2, X may be the same or different. ) is used directly, or the substituted nitrobenzene of formula (I) produced in the reaction system is used without isolation and treated with an alkali metal salt or an alkali in a polar organic solvent. General formula (II), which is reacted in the presence of metal hydroxide ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) (The symbol in the formula is (I)
A method for producing a substituted diphenyl ether represented by the formula (having the same meaning as the formula).