JPH0761939A - Method for producing aromatic fluorine compound - Google Patents

Abstract

(57) [Summary] [Objective] A method for highly selectively obtaining an aromatic fluorine compound from an aromatic amino compound (particularly one having a polar group such as a hydroxyl group or an alkoxy group at the ortho or para position with respect to the amino group). I will provide a. [Structure] An aromatic amino compound is diazotized in a solution consisting of anhydrous hydrofluoric acid and an organic base by a nitrous acid-providing agent, and then the resulting diazonium salt has a standard redox potential of −2 V or more +0. A method for producing an aromatic fluorine compound, which comprises thermally decomposing in the presence of a metal salt (tin salt, samarium salt, or the like) of 2 V or less.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing an aromatic fluorine compound. The aromatic fluorine compound is
It is an extremely important compound as an intermediate raw material for functional materials such as pharmaceuticals, agricultural chemicals, liquid crystals and dyes.

[0002]

2. Description of the Related Art Conventionally, a method for producing an aromatic fluorine compound by a diazotization reaction of an aromatic amino compound and a thermal decomposition reaction (dediazofluorination reaction) of a generated diazonium salt in anhydrous hydrofluoric acid has been carried out. Known for a long time (GA
Olah et al., J. Org. Chem., 44 (1979) 3872.).

The inventors of the present invention have also proposed some methods for producing an aromatic fluorine compound using this reaction (Japanese Patent Laid-Open Nos. 61-63627 and 63-18).
8631, JP-A-1-233232). According to these methods, the target aromatic fluorine compound can be obtained in a relatively high yield in one step by a diazotization reaction and a dediazofluorination reaction from an aromatic amino compound.

[0004]

However, a diazonium salt of an aromatic amino compound having a polar group such as a hydroxyl group, an alkoxy group, a nitro group, an amino group, and a halogen group in the ortho position or the para position with respect to the amino group is However, a high thermal decomposition temperature is required due to the contribution of the resonance structure. Therefore, in the reaction of these aromatic amino compounds having a polar group, the formation of various by-products due to the high temperature thermal decomposition reaction is unavoidable, and a satisfactory high reaction yield cannot be obtained. The present invention aims to solve such problems.

[0005]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that an aromatic amino compound is added to a nitrous acid-providing agent in a solution containing anhydrous hydrofluoric acid and an organic base. To diazotize, and then the resulting diazonium salt has a standard redox potential of −2 V or more +0.
It was found that an aromatic fluorine compound can be highly selectively obtained by thermal decomposition in the presence of a metal salt of 2 V or less,
The present invention has been reached. The present invention will be described in detail below.

The structure of the aromatic amino compound that can be used in the production method of the present invention is not particularly limited and is a compound having one or more amino groups as a substituent on the aromatic ring. Further, the aromatic ring may be substituted with an alkyl group, a perfluoroalkyl group, an alkoxy group, a hydroxyl group, an acyl group, an acyloxy group, a carboalkoxy group, a dialkylamino group, a nitro group or a halogen group. Further, it may be condensed with another aromatic ring.

Of these aromatic amino compounds, the diazonium salt of an aromatic amino compound having a polar group such as a hydroxyl group, an alkoxy group, a nitro group, an amino group or a halogen group at the ortho or para position with respect to the amino group is , A high pyrolysis temperature is required due to the contribution of its resonance structure. The effect of the present invention is particularly remarkable for the substrates requiring these high thermal decomposition reaction temperatures.

These aromatic amino compounds undergo a diazotization reaction in a solution of anhydrous hydrofluoric acid and an organic base, with a nitrous acid-providing agent acting on them. Hydrofluoric anhydride is used in an amount of 3 to 200 times mol, preferably 5 to 100 times mol, of the aromatic amino compound. The organic base may be a Lewis base containing a nitrogen, oxygen, sulfur or phosphorus atom, and its structure is not particularly limited, but a tertiary amine is particularly preferable. Specific examples include pyridine, quinoline, lutidine, N-dimethylaniline, triethylamine and 2-halopyridine. The use of these organic bases has the advantages that the target product can be easily extracted and separated, and the tar-forming reaction is reduced. The amount used is 1 to 80% by weight, preferably 5 to 50% by weight, based on anhydrous hydrofluoric acid.

The nitrous acid-providing agent is not particularly limited as long as it is a nitrous acid-providing agent usually used for diazotization of an amino group.
Alkali metal nitrites, alkyl nitrites, nitrosyl compounds (NOX; here, X represents Cl, F, HSO _4, etc.), anhydrous nitrous acid and the like are preferably used. Specific examples include sodium nitrite, potassium nitrite, amyl nitrite, butyl nitrite, nitrosylsulfuric acid, N ₂ O ₄ , N ₂ O _{3 and the} like. The amount used is 0.5 to 10 equivalents, preferably 1 to 3 equivalents, relative to the aromatic amino compound.

The reaction temperature of the diazotization reaction is -20 to +20.
C., preferably in the range of −10 to + 10 ° C. from the viewpoint of reaction rate. After the completion of the diazotization reaction, a metal salt having a standard oxidation-reduction potential of −2 V or more and +0.2 V or less is added, and then the reaction solution is heated as it is for thermal decomposition (dediazofluorination reaction).

The thermal decomposition reaction of the produced diazonium salt is
By adding the metal salt under the above conditions, the thermal decomposition reaction start temperature is lowered, and it becomes possible to suppress the production of by-products due to the high thermal decomposition reaction temperature, and the desired aromatic fluorine is obtained at a high reaction yield. The compound can be obtained. this is,
The usual thermal decomposition reaction of a diazonium salt proceeds by an ionic mechanism involving a heterolytic cleavage reaction as shown in the formula (1), whereas there is a metal salt whose standard redox potential is lower than + 0.2V. In that case, the one-electron reduction reaction of the diazonium salt with the metal salt proceeds, and the decomposition reaction proceeds with a radical mechanism involving a homolytic cleavage reaction as shown in formula (2). However, it is considered that this is because the decomposition reaction of the diazonium salt becomes possible.

[0012]

[Chemical 1]

The metal salt exhibiting such an action is as follows:
A metal salt having a standard oxidation-reduction potential of +0.2 V or less is effective, but a metal salt having a standard oxidation-reduction potential of less than -2 V is not preferable because a reduction reaction other than the intended dediazofluorination reaction becomes remarkable. Therefore, the metal salt used in the present invention has a standard redox potential of −2 V or more and +0.2 V.
The following metal salts.

Specific metal salts include tin (II) [+
0.154V], cobalt (II) [+ 0.195V],
Chromium (II) [-0.424V], Samarium (II)
Examples thereof include halides such as [−1.55V], acetates, and hydroxides. Incidentally, the cuprous salt Cu (I) known in the Sandmeyer reaction has a standard oxidation-reduction potential of +.
0.153V, but Cu (0) and Cu whose standard redox potential is + 0.337V in anhydrous hydrofluoric acid
(II) disproportionated and does not exist stably (HM
Haendler, J. Am. Chem. Soc., 76 (1954) 2178.), So no effect is observed in this reaction system.

The amount of these metal salts added may be such that the diazonium salt can be reduced by one electron. For example, a two-electron reducing agent Sn (II) salt [Sn (II) → Sn (I
V)] is used in an amount of 0.5 times equivalent or more based on the diazonium salt. Furthermore, in this dediazofluorination reaction process, by adding a highly nucleophilic F anion source together with the above metal salt, higher selectivity of the aromatic fluorine compound is exhibited. Preferred examples of the highly nucleophilic F anion source are tetraalkylammonium fluoride HF salts, specifically, compounds such as nBu ₄ N ⁺ F ⁻ (HF) _m [m = 1, 2]. To be The amount added is
It is 0.1 to 5 times equivalent, preferably 0.5 to 1.5 times equivalent to the diazonium salt.

The present invention can also be carried out in a solvent.
In this case, the solvent is preferably an aprotic organic solvent such as diethyl ether, tethydrofuran or acetonitrile. The start and end of the thermal decomposition reaction can be easily confirmed by the generation of nitrogen gas. Separation of the product after the reaction is easily carried out by adding a large amount of water to the reaction solution, separating the product by extraction, and then subjecting it to distillation, recrystallization, chromatography and the like.

[0017]

EXAMPLES Next, the present invention will be described in more detail by way of examples, but the present invention is not limited to the following examples without departing from the gist thereof.

Example 1 59 ml of a pyridine / anhydrous hydrofluoric acid solution having a weight ratio of 40/60% was placed in a cooled Teflon reactor, and 3 g of p-aminophenol (30 mmo) was added at about 0 ° C. with stirring.
l) was added and the sodium nitrite was continuously added at 5.degree.
5 g (31.5 mmol) was added. 3 below 10 ° C
The reaction was stirred for 0 minutes. Then 6.82 g of SnCl ₂
(36 mmol) was added and the diazonium salt was thermally decomposed at 100 ° C. for 3 hours. After completion of the thermal decomposition, the reaction solution was cooled and ice water and methylene chloride were added to extract the product.
As a result of analyzing the organic layer after washing with water, the conversion rate of the diazonium salt was 96% and the yield of the target p-fluorophenol was 83% (selectivity = 86%).

Example 2 The same operation as in Example 1 was performed except that the amount of SnCl ₂ added was 3.41 g (18 mmol). The conversion of the diazonium salt was 92%, and the yield of the target p-fluorophenol was 76% (selectivity = 82%).

Example 3 Instead of SnCl ₂ , SmI ₂ in THF (36 mm
ol) was added, and the same operation as in Example 1 was performed. The conversion rate of the diazonium salt was 90%, and the yield of the target p-fluorophenol was 68% (selectivity = 7.
5%).

Example 4 At the time of thermal decomposition of a diazonium salt, n was added together with SnCl ₂ .
The same operation as in Example 1 was performed except that Bu ₄ N ⁺ F ⁻ (HF) ₂ (36 mmol) was added. The conversion of the diazonium salt was 100%, and the yield of the target p-fluorophenol was 92% (selectivity = 92%).

Comparative Example 1 By the operation of Example 1, the thermal decomposition reaction of the diazonium salt was carried out without adding SnCl ₂ . As a result, the conversion rate of the diazonium salt was 76%, and the target p-fluorophenol yield was 41% (selectivity = 59%).

Comparative Example 2 Instead of SnCl ₂ , the standard redox potential was +0.15.
As a Cu (I) salt of 3 V, CuCl (36 mmo
The same operation as in Example 1 was performed except that l) was added. The conversion rate of the diazonium salt was 89%, and the yield of the target p-fluorophenol was 43% (selectivity = 4.
8%).

Comparative Example 3 The standard redox potential was +0.77 instead of SnCl _2.
The same operation as in Example 1 was performed except that FeCl ₂ was added as the Fe (II) salt of 1V. The conversion rate of the diazonium salt was 79%, and the yield of the target p-fluorophenol was 26% (selectivity = 33%).

Comparative Example 4 Instead of SnCl ₂ , the standard redox potential was -2.37.
The same operation as in Example 1 was carried out except that Mg (0) powder of V was added. Conversion rate of diazonium salt is 75%
And the target yield of p-fluorophenol is 2
It was 6% (selectivity = 34%).

Comparative Example 5 The procedure of Example 1 was repeated except SnCl₂Instead of adding
nBu_FourN⁺F^-(HF) ₂(36 mmol) was added to
A thermal decomposition reaction of the azonium salt was performed. As a result, diazo
The conversion rate of the aluminum salt is 78%, and the target p-full
The yield of orophenol was 42% (selectivity = 54%).
It was.

[0027]

According to the method of the present invention, an aromatic fluorine compound can be obtained with high selectivity.

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Claims (3)

[Claims] 1. An aromatic amino compound is diazotized by reacting it with a nitrite-providing agent in a solution consisting of anhydrous hydrofluoric acid and an organic base, and then the resulting diazonium salt has a standard redox potential of -2 V. A method for producing an aromatic fluorine compound, which comprises thermally decomposing in the presence of a metal salt of +0.2 V or less. 2. The standard redox potential is −0.2 V or more and +0.2.
The method for producing an aromatic fluorine compound according to claim 1, wherein the metal salt of V or less is a tin salt or a samarium salt. 3. An aromatic amino compound having at least one polar group selected from a hydroxyl group, an alkoxy group, a nitro group, an amino group and a halogen group at the ortho or para position with respect to the amino group. The method for producing an aromatic fluorine compound according to claim 1, wherein