JPS644501B2 - - Google Patents

Description

[Detailed description of the invention]

In the present invention, aromatic phenols represented by the general formula ArOH (wherein Ar represents an aromatic residue) are reacted with chlorodifluoromethane to produce the general formula ArOCHF ₂
Regarding the method for producing aryl difluoromethyl ethers represented by (wherein Ar is the same as above),
In particular, the reaction is carried out in an aprotic, strongly polar solvent in the presence of a basic catalyst. In general, the method for producing the corresponding aryl difluoromethyl ethers by reacting phenols with chlorodifluoromethane is to dissolve the phenols in a large excess of concentrated alkaline water, add dioxane as a solvent, and then react the phenols with chlorodifluoromethane. A method has been adopted in which methane is introduced at 60 to 90℃, and detailed reports on this can be found, for example.
Journal of Organic Chemistry.Volume 25 (1966)
Described on pages 2009-2012. This reaction requires the presence of a large excess of a strong alkaline aqueous solution and dioxane as a solvent, and chlorodifluoromethane is also decomposed by strong alkalis, and side reactions other than those used in the original reaction occur at a considerable rate. This is not necessarily an advantageous method in terms of effective use of expensive chlorodifluoromethane. Furthermore, with this method, it is difficult to recover dioxane as a solvent. Under these circumstances, we investigated various methods for producing aryl difluoromethyl ethers and found that aromatic phenols and chlorodifluoromethane were reacted to produce the desired aryl difluoromethyl ethers in large excess. They have now invented a method that does not require a strong base and allows this reaction to proceed extremely well in a substantially non-aqueous system. In other words, we have found that when a highly polar aprotic solvent is used as a solvent in the reaction, the desired reaction proceeds extremely well in the coexistence of an equimolar or small excess of a basic substance. . The highly polar aprotic solvent mentioned here has a dielectric constant (ε) of 15 or more, a dipole efficiency (μ) of 2.5D or more, and an E _T (30) value, which is one of the solvent polarity parameters. 40 to 47. Typical examples of these solvents are:
For example, dimethylsulfoxide (DMSO), dimethylformamide (DMF), diethylformamide, dimethylacetamide, diethylacetamide, propylene carbonate, ethylene carbonate, acetonitrile, sulfolane, dimethylsulfolane, dimethylsulfone, acetone, acetophenone, nitrobenzene, benzonitrile,
Examples include 1-methyl-2-pyrrolidine, tetramethylurea, and the like. Even if these solvents contain a small amount of water or other organic solvents, it will not have a major effect, and usually 50 to 100% content can be used. As the basic substance, alkali metal hydroxides, carbonates, and bicarbonates are used. For example, relatively weak bases such as potassium carbonate, sodium carbonate, potassium bicarbonate, and sodium bicarbonate can be used, and strong bases such as caustic soda and caustic potash can also be used. Although there are no strict restrictions on the amount used, it is usually advisable to use 1 to 4 moles of the basic substance relative to the phenol. Chlorodifluoromethane may be directly blown into the above solvent, aromatic phenols, and a mixture of basic substances, or may be pressurized into an autoclave and raised to the reaction temperature for reaction. The reaction may be carried out using a reaction tank. In either case, the amount used is not particularly limited, but it is preferable to use chlorodifluoromethane in an amount of 1 to 10 times the mole of the phenol. The reaction conditions depend on the type of aromatic phenol and basic substance used, but are generally room temperature or 150℃.
℃ range, preferably 50℃ or
It is appropriate to carry out the reaction in the range of 120°C. The method of the present invention can be applied to the production of a very wide range of aryl difluoromethyl ethers. For example, the aromatic residue represented by Ar in the above general formula may include a phenyl group, a naphthalene group, a halogen atom, a nitro a phenyl group substituted with one or two substituents consisting of a group, an alkyl group, an alkenyl group, an alkoxy group, an alkenyloxy group, an aralkyl group, an aralkyloxy group, a cyano group, a carboxyl group, an alkoxycarbonyl group or a carbamoyl group Alternatively, a naphthalene group, etc. may be mentioned. When this manufacturing method is compared with conventional manufacturing methods, it has the following advantages and is an extremely superior method from an industrial perspective. First, since the reaction can be carried out in a non-aqueous system, the solvent can be distilled off after the reaction is completed and reused as is, allowing efficient use of expensive solvents. Second, chlorodifluoromethane used in excess hardly causes any side reactions, and recovery of the excess is extremely easy, making it possible to effectively use expensive chlorodifluoromethane. Third, unreacted aromatic phenols form salts with basic substances and become insoluble in common solvents such as toluene, so they can be easily separated from the product as insoluble solids by appropriate solvent extraction. It is possible to significantly reduce the burden of phenolic wastewater in the separation and purification process. Furthermore, the amount of basic substances used is extremely small compared to conventional methods, which not only improves economy but also significantly reduces the burden of wastewater treatment. Below, typical examples of the method of the present invention will be shown, and the method of the present invention will be explained in more detail. However, these examples are merely illustrative examples of typical ones, and it goes without saying that the method of the present invention is not limited to these only, and is not limited in any way by these examples. . Examples 1 to 7 0.1 mole of the phenols shown in Table-1
It was added to a mixed solution of 200 ml of DMF and 0.2 mol of anhydrous potassium carbonate, and placed in an autoclave, into which 0.3 mol of chlorodifluoromethane was pressurized. after that
The reaction was carried out at 100°C for 3 hours, and after the reaction was completed, the pressure was returned to normal to remove excess chlorodifluoromethane. After distilling off DMF under reduced pressure, toluene was added, and the organic layer was diluted with alkaline water (5% caustic soda aqueous solution). After washing with water and water, toluene was distilled off, and the product was further distilled under reduced pressure. Table 1 shows the yield of the target product.
It was shown to. The yields listed in the reference examples are from the Journal of Organic
The yield was as described in Chemistry, Vol. 25, pp. 2009-2012 (1960).

[Table] Examples 8 to 12 12.3 g (0.1 mol) of paranitrophenol was added to 200
Dissolve in ml of DMF, add various basic substances, and incubate at 100℃.
Then, chlorodifluoromethane was introduced at normal pressure for 2 hours to cause a reaction. After the reaction was completed, DMF was distilled off, 300 ml of toluene was added, the toluene was distilled off after washing with alkaline water and water, and the product was heated to 105°/
Paradifluoromethoxynitrobenzene was obtained by vacuum distillation at 6 minHg. The results are shown in Table-2.

【table】

[Table] Example 13 Paranitrophenol in a glass autoclave
12.3g (0.1 mol), anhydrous potassium carbonate 13.8g (0.1
mol) and 220 ml of DMF were added, and 26 g (0.3 mol) of chlorodifluoromethane was introduced under pressure. This was thoroughly stirred, kept at 100℃ for 3 hours to react, and then returned to normal pressure to remove excess chlorodifluoromethane.
Furthermore, the temperature was returned to room temperature, insoluble substances were removed, and the liquid was concentrated under reduced pressure to recover DMF. Toluene 200% to the residue
After adding ml, wash twice with 50ml of 5% caustic soda,
After further washing with 50 ml of water, toluene was removed under reduced pressure. Distilling the residue under reduced pressure yields the desired paradifluoromethoxynitrobenzene at 106°/6 mmHg.
Obtained 14.2g. The yield was 75%. Example 14 Ortho-[N-(3,4-dichlorophenyl)carbamoyl]-phenol 5 g, potassium carbonate 2.4
A mixture of g and 50 ml of DMF was heated to 100°C, and chlorodifluoromethane was introduced into the system for 4 hours to cause a reaction. After the completion of the reaction, DMF was distilled off, toluene was added, this toluene layer was washed with alkaline water and water, and then toluene was distilled off. The residue was recrystallized with a mixed solvent of benzene and hexane to obtain 3.8 g of N-( 3,4-dichlorophenyl)-orthodichloromethoxy was obtained. The yield was 59%. Example 15 A mixed solution of 14 g (0.1 mol) of paranitrophenol, 28 g (0.1 mol) of potassium carbonate, and 200 ml of DMSO was heated to 100° C., and chlorodifluoromethane was introduced for 3 hours to cause a reaction. After the reaction was completed, the solvent was distilled off, 200 g of toluene was added, the insoluble matter was removed, the toluene layer was washed with alkaline water and water, the toluene was distilled off, and further distilled under reduced pressure.
11.3g of paradifluoromethoxynitrobenzene was obtained as a fraction of 103-106°C/6mmHg. yield
It was 59.7%. Similar reaction was carried out using 200ml of N,N instead of DMSO.
- Dimethylacetamide was used to obtain paradifluoromethoxynitrobenzene with an isolated yield of 67%.

Claims (1)

[Claims] 1. General formula ArOH (in the formula, Ar represents an aromatic residue)
The aromatic phenol represented by is reacted with chlorodifluoromethane in an aprotic strongly polar solvent in the presence of a basic _catalyst . A method for producing aryl difluoromethyl ether. 2 The aprotic strong polar solvent has a melting rate (ε)
15 or more, dipole efficiency (μ) 2.5D or more, E _T (30) value, which is one of the solvent polarity parameters, is 40 to 47.
The manufacturing method according to claim 1, wherein the solvent has the following. 3. The production method according to claim 1, wherein the basic catalyst is at least one of alkali metal hydroxides, carbonates, and bicarbonates.