JPH043380B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing O-arylhydroxylamine, which is useful as a synthetic intermediate for pharmaceuticals and agricultural chemicals. Conventionally, O-arylhydroxylamine was prepared by combining potassium salts of phenols and hydroxylamine-
A method of reacting with O-sulfonic acid is known [Chemistry and Industry, p. 559 (1962
); Journal of Chemical Society Perkin I,
1827 pages (1977)]. However, the target O
-Yield of arylhydroxylamine is at most 15%
Moreover, depending on the type of benzene ring substituent of the phenol, the desired product may not be obtained at all, and this is not a general method for synthesizing O-arylhydroxylamines. Also, recently, O-
It has been reported that arylhydroxylamines can be obtained in relatively good yields by reacting potassium salts of phenols with O-mesitylenesulfonylhydroxylamines (Synthesis, 461).
(1980)). However, O-mesitylenesulfonylhydroxylamine is unstable and many explosions have been reported [for example, Chemical
Engineering News, Volume 51, December 17 issue, Page 36 (1977); Journal of Organic Chemistry, 42
Volume, 376 pages (1977); Journal of Chenical
Society, Perkin I, p. 1826 (1980);
Synthesis, p. 801 (1980)], so this method cannot be used as an industrial manufacturing method either. Therefore, O-
Until now, it has been impossible to supply large quantities of arylhydroxylamines to the pharmaceutical and agrochemical manufacturing industries. In view of the above-mentioned circumstances, the present inventors conducted intensive research for the purpose of developing a general and safe industrial synthesis method for O-arylhydroxylamine, and as a result, completed the present invention. That is, the present invention provides an alkali metal salt of a phenol represented by the general formula (), ArOM () (in the formula, Ar represents an aryl group and M represents an alkali metal. The same applies hereinafter); (In the formula, n is an integer from 1 to 3, X is hydrogen,
represents a halogen, a lower alkyl group, or a lower alkyl group substituted with a halogen, and (5-n) X are:
They may be the same or different. The gist thereof is a method for producing an O-arylhydroxylamine represented by the general formula (), ArONH ₂ (), which is characterized by reacting a compound represented by the formula () with a compound represented by the formula (). The present invention will be explained in detail below. The production method of the present invention can be expressed as a reaction formula using a general formula as follows. In the method of the present invention, an alkali metal salt of a phenol represented by the general formula ArOM () is used. Examples of the phenols used as raw materials for the metal salt include phenol, fluorophenol, difluorophenol, trifluorophenol, chlorophenol, dichlorophenol, trichlorophenol, bromophenol, dibromophenol, tribromophenol, and iodophenol. , diiodophenol, chlorofluorophenol, dichlorofluorophenol, chlorodifluorophenol, bromochlorophenol, bromodichlorophenol and other halogenated phenols; cresol, xylenol, trimethylphenol, ethylphenol, diethylphenol, propylphenol and other alkylphenols. alkoxyphenols such as methoxyphenol, dimethoxyphenol, ethoxyphenol, and propyloxyphenol; alkoxyalkylphenols such as methoxymethylphenol and methoxyethylphenol; alkenylphenols such as vinylphenol, divinylphenol, propenylphenol, and allylphenol; Alkynylphenols such as bropargylphenol, alkoxycarbonylphenols such as methoxycarbonylphenol, dimethoxycarbonylphenol, ethoxycarbonylphenol, diethoxycarbonylphenol, alkoxycarbonylalkylphenols such as methoxycarbonylmethylphenol, methoxycarbonylethylphenol, Acyloxyphenols such as acetoxyphenol and propionyloxyphenol, fluoromethylphenol, difluoromethylphenol, trifluoromethylphenol,
Haloalkylphenols such as chloroethylphenol, alkyl-substituted nitrophenols such as cyanophenol, nitrophenol, methylnitrophenol, dimethylnitrophenol, halogen-substituted nitrophenols such as fluoronitrophenol and chloronitrophenol, trifluoromethylnitrophenol haloalkyl-substituted nitrophenols such as methylfluorophenol, alkyl-substituted halogenated phenols such as methylchlorophenol, halogenated alkyl-substituted halogenated phenols such as fluorotrifluoromethylphenol, chlorotrifluoromethylphenol, phenylphenol, Aryl-substituted phenols such as substituted phenylphenols, phenoxyphenols, aryloxyphenols such as substituted phenoxyphenols, arylalkylphenols such as benzylphenols and substituted benzylphenols, 5
-, 6-, 7- or 8-hydroxychroman (substituents may be present), 5-, 6-, 7- or 8-hydroxycoumarin (substituents may be present), 5-, 6-, 7- or 8-hydroxy-3,4-dihydrocoumarin (with or without substituents), 5-, 6-, 7- or 8-hydroxy-2H-chromene (with or without substituents) good), 5
-,6-,7- or 8-hydroxy-4H-chromene (substituents may be present), naphthol,
Halogenated naphthols such as fluoronaphthol, difluoronaphthol, trifluoronaphthol, chloronaphthol, dichloronaphthol, trichloronaphthol, bromonaphthol, dibromonaphthol, chlorofluoronaphthol, dichlorofluoronaphthol, chlorodifluoronaphthol, methylnaphthol, dimethylnaphthol, ethyl Examples include alkylnaphthols such as naphthol and diethylnaphthol, and haloalkylnaphthols such as fluoromethylnaphthol, difluoromethylnaphthol, and trifluoromethylnaphthol. Further, in the general formula (), examples of the alkali metal represented by M include lithium, sodium, potassium, etc., with sodium or potassium being particularly preferred. In addition, the alkali metal salts of phenols represented by the general formula () include the phenols and alkali metal hydroxides (NaOH, KOH, etc.), alkali metal alkoxides (NaOMe, NaOEt, NaOBu, etc.).
KOMe, KOEt, KOBu, etc.), alkali metal hydrides (LiH, NaH, KH, etc.), alkali metal amides (LiNH ₂ , NaNH _2, etc.), or alkali metal alkyls (MeLi, BuLi, etc.) by known methods. The phenols may be synthesized and isolated for use, or the phenols may be dissolved in a solvent and alkali metal hydroxides (NaOH,
KOH, etc.), alkali metal alkoxides (NaOMe, NaOEt, NaOBu ^t , KOMe, KOEt,
KOBu ^t, etc.), alkali metal hydrides (LiH,
It is generated in the reaction system by adding an alkali metal amide (such as NaH, KH, etc.), an alkali metal amide (such as LiNH ₂ , NaNH ₂ ), or an alkali metal alkyl (such as MeLi, BuLi), and can be used in the reaction as is without isolation. It's okay. Specifically, the compound represented by the general formula () includes, for example, O-(nitrophenyl)hydroxylamines, O-(chloronitrophenyl)
Hydroxylamines, O-(fluoronitrophenyl(hydroxylamines), O-(dichloronitrophenyl)hydroxylamines, O-
(nitrotrifluoromethylphenyl)hydroxylamines, O-(dinitrophenyl)hydroxylamines, O-(chlorodinitrophenyl)
Examples include hydroxylamines, O-(trinitrophenyl)hydroxylamines, O-(methylnitrophenyl)hydroxylamines, and the like. Among these, it is particularly preferable to use those having nitro groups at the 2-, 4-, and 6-positions of the phenyl group. The compound represented by the general formula () can be prepared, for example, by the method of the following formula shown in "Method for producing nitrophenoxyamines" filed by the applicant on the same date, (wherein, X and n are the same as above) or Journal of Heterocyclic Chemistry,
The formula method described in Volume 4, page 413 (1967), It can be easily manufactured by, for example, Although the reaction between the general formulas () and () can be carried out without a solvent, it is preferable to use a solvent. Suitable solvents for the reaction include, for example, dimethylformamide, dimethylacetamide, N
- Aprotic polar solvents such as methylpyrrolidone and hexamethylphosphoramide, ethers such as ethyl ether, isopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diglyme, alcohols such as methanol, ethanol, propanol, and butanol, benzene, It is an aromatic hydrocarbon such as toluene or xylene, and may contain a small amount of water, for example, about 10% or less. Among the above solvents, aprotic polar solvents are particularly preferred. The reaction is usually ()
This is carried out by mixing () at a ratio of 0.1 to 5 mol, preferably 0.3 to 2 mol, based on the mole. When a solvent is used, it is effective to use 1 to 30 parts by weight per 1 part by weight of the solvent. The reaction temperature is generally -20 to 200°C, preferably 0 to 120°C. In addition, the reaction time is arbitrary, but usually 0.1 to 10 hours,
Preferably it is about 0.2 to 3 hours. After the reaction is complete, the desired general formula ArONH ₂ ()
To isolate the O-arylhydroxylamine represented by It is.
However, further purified () can be obtained by appropriately employing ordinary purification means such as recrystallization and distillation. It can also be isolated as a hydrohalide salt of () by blowing hydrogen halide gas into an organic solvent solution containing (). Next, the present invention will be specifically explained using examples. Example 1 19.8g (0.15mol) of potassium salt of phenol
After dissolving in 100 ml of dimethylformamide at 50°C, a solution of 19.9 g (0.1 mol) of O-(2,4-dinitrophenyl)hydroxylamine in 30 ml of dimethylformamide was added dropwise over 15 minutes. After the dropwise addition was completed, the mixture was further stirred at 50°C for 1 hour. After cooling the reaction mixture to room temperature, 200 ml of water was added and extracted with ethyl acetate. The extract was washed with a 5% aqueous sodium hydroxide solution and then with saturated brine, and then dried over anhydrous magnesium sulfate. When ethyl acetate is distilled off, O-
7.8 g of phenylhydroxylamine was obtained (yield 72%). Example 2 The reaction was carried out in the same manner as in Example 1 except that 17.4 g (0.15 mol) of the sodium salt of phenol was used instead of the potassium salt of phenol.
-6.5g of phenylhydroxylamine was obtained (60% yield). Examples 3 to 6 The reaction was carried out in the same manner as in Example 1, except that the solvents listed in Table 1 were used instead of dimethylformamide. Table 1 shows the yield of the O-phenylhydroxylamine obtained.

[Table] Examples 7 to 51 A reaction was carried out in the same manner as in Example 1 except that Ar shown in Table 2 was used instead of the phenyl group as Ar in ArOM. Table 2 shows the results.
Shown below.

【table】

【table】

【table】

【table】

【table】

【table】 Examples 51-55 In Example 1

A reaction was carried out in the same manner as in Example 1, except that the compound shown in Table 3 was used in place of O-(2,4-dinitrophenyl)hydroxylamine as [Formula], and the reaction temperature was changed to 100°C. The results are shown in Table 3.

【table】

【table】 Example 56 In Example 1

The reaction was carried out in the same manner as in Example 1 except that O-picrylhydroxylamine was used instead of O-(2,4-dinitrophenyl)hydroxylamine as the formula and the reaction temperature was 20°C. The yield of O-phenylhydroxylamine obtained was 81%.

Claims (1)

[Scope of Claims] 1 An alkali metal salt of a phenol represented by the general formula (), ArOM () (in the formula, Ar represents an aryl group and M represents an alkali metal. The same applies hereinafter); ), (In the formula, n is an integer from 1 to 3, X is hydrogen,
Indicates a halogen, a lower alkyl group, or a lower alkyl group substituted with a halogen. 1. A method for producing O-arylhydroxylamine represented by the general formula (), ArONH ₂ (), which comprises reacting the O-arylhydroxylamine with a compound represented by the formula ().