JPH02134335A - Production of p-fluorophenol - Google Patents

Abstract

PURPOSE:To safely obtain the subject compound in high yield and high purity on an industrial scale by diazotizing p-aminophenol with an alkyl nitrite in the presence of an aqueous solution of hydrofluoric acid having a specific concentration and heat-decomposing the resultant diazonium salt. CONSTITUTION:p-Aminophenol of formula I is reacted with a diazotizing agent in the presence of hydrogen fluoride and the obtained diazonium salt of formula II is subjected to thermal decomposition usually at about 20-200 deg.C, preferably at about 30-150 deg.C to obtain p-fluorophenol of formula III useful as all intermediate for pharmaceuticals, agricultural chemicals or dyes. In the above process, the diazotizing reaction is carried out with an alkyl nitrite of formula IV (R is CnH2n+1; n is integer of >=1) in the presence of an aqueous solution of hydrofluoric acid having a concentration of 40-90wt.% at -100 to +150 deg.C, preferably -80 to +100 deg.C. The objective compound can be produced in high purity and yield at a low cost.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing p-fluorophenol.

p-Fluorophenol is a compound that has recently been gaining attention as an intermediate raw material for medicines, agricultural chemicals, or dyes, and its range of applications has expanded in recent years.

[Prior art and problems to be solved by the invention] p-fluorophenol is a type of aromatic fluorine compound,
As a conventional method for producing aromatic fluorine compounds, a method using a diazotization reaction of an aromatic amine and a thermal decomposition reaction of a diazonium salt obtained by this nocyazotization reaction, a method using the so-called Ziemann reaction, is well known. .

The first stage diazotization reaction in this production method is a reaction in which diazotization is performed using sodium nitrite in the presence of borofluoric acid or anhydrous hydrofluoric acid at low temperature to produce a diazonium salt of an aromatic amine. In the second stage reaction, the diazonium salt obtained in the first stage reaction is
This is a reaction in which the target aromatic fluorine compound is obtained by thermal decomposition at a temperature of about 00°C.

However, when this production method is applied to produce P-fluorophenol, there are the following problems. That is, when p-aminophenol is used as an aromatic amine and diazotized with sodium nitrite in the presence of anhydrous hydrofluoric acid, the yield of p-fluorophenol is extremely low at less than 30%, and solid Cane Sodium Acid Fluoride (NaH
Fz) is produced in large amounts as a by-product, and this by-produced NaH
This has industrially disadvantageous problems, such as Fz sticking to the reaction vessel and the stirrer, interfering with smooth operation.

[Means to solve the problem]

The present inventors have solved the above-mentioned problems caused by the diazotization reaction and thermal decomposition reaction of p-aminophenol, the so-called Dieman reaction, and have succeeded in producing p-aminophenol without producing by-products such as NaHFt. As a result of extensive research to establish a method for industrial production with high yield, we found that when diazotizing p-aminophenol, we used aqueous hydrofluoric acid solution of a specific concentration and using submersible chloride as a diazotizing agent. The present inventors have discovered that the above object can be achieved by using alkyl nitrate, and have completed the present invention.

That is, the present invention provides a method for producing p-fluorophenol by reacting p-aminophenol with a diazotizing agent in the presence of hydrogen fluoride and thermally decomposing the resulting diazonium salt. The present invention provides a method for producing p-fluorophenol, characterized in that a diazotization reaction is carried out using an alkyl nitrite in the presence of a ~90% by weight aqueous hydrofluoric acid solution.

[Detailed disclosure of the invention]

The present invention will be explained in more detail.

The alkyl nitrite used in the present invention has a general formula of R-O.
A compound represented by NO, in this formula R is C7H1
It is an alkyl group represented by a+1 (where n is a positive integer of 1 or more). As such alkyl nitrite,
Methyl nitrite, ethyl nitrite, n-propyl nitrite, isopropyl nitrite, n-butyl nitrite, isobutyl nitrite, 5ee-butyl nitrite, tert-butyl nitrite,
n-amyl nitrite, isoamyl nitrite, ter nitrite
Examples include t-amyl and the like.

In the present invention, first, p-aminophenol is used at a concentration of 40 to 90% by weight (hereinafter, % by weight is simply abbreviated as %).
It is necessary to diazotize using an alkyl nitrite in the presence of an aqueous solution of hydrofluoric acid to generate a diazonium salt, and the diazonium salt is generated according to the following formula (11).

In the above diazotization reaction, the ratio of alkyl nitrite to p-aminophenol is 1
The amount is 1 to 3 mol, preferably 1.1 to 2 mol. Further, the amount of the hydrofluoric acid aqueous solution used is 1 to 50 mol, preferably 10 to 50 mol, per 1 mol of p-aminophenol.
~30 moles.

In the present invention, the concentration of the hydrofluoric acid aqueous solution used during the diazotization reaction is particularly important.

If the concentration of the aqueous solution is less than 40%, the reaction rate will decrease and hydroquinone will be produced as a by-product, whereas if the concentration exceeds 90%, a tar-like substance will be produced as a by-product, and both of them will reduce the target p-
This is disadvantageous because the yield of fluorophenol decreases.

In the present invention, the above-mentioned diazotization reaction is usually carried out from -100 to 15
It is carried out at a temperature of 0°C, preferably -80 to 100°C. Further, the reaction time may vary depending on the reaction temperature, but is usually about 10 minutes to 10 hours, preferably about 15 minutes to 5 hours.

Incidentally, it is preferable to carry out the diazotization reaction in a suitable organic solvent because the reaction can be easily controlled. As the organic solvent at this time, aprotic polar solvents are suitable, and representative examples include acetonitrile, tetrahydrofuran, N, N-
Dimethylacetamide, N,N-dimethylformamide, N-methyl-2-pyrrolidone, 1,3-dimethyl-2
Preferred examples include -imidazolidinone, dimethyl sulfoxide, dimethyl sulfone, and tetramethylene sulfone.

There is no particular limitation on the amount of organic solvent used, but if the amount used is too large, the burden on the recovery process of the organic solvent after the reaction will increase, which is undesirable. Therefore, in the present invention, the amount of organic solvent used is , usually 1 for p-aminophenol
It is carried out in a range of about 10 to 10 times the weight.

By heating the diazonium salt thus obtained, the desired p-fluorophenol can be easily obtained through the thermal decomposition reaction shown in the following formula (2).

In the present invention, this thermal decomposition reaction may be carried out after separating the diazonium salt from the reaction solution containing the diazonium salt obtained by the diazotization reaction, but the above thermal decomposition reaction is usually carried out at a temperature of about 20 to 200°C. Preferably 30-15
Since the reaction is carried out at a temperature of about 0°C, the reaction solution containing the above diazonium salt is heated to produce p-fluorophenol, and then separated by distillation or other operations to produce the desired p-fluorophenol. The method of obtaining is preferred.

The reaction time during the thermal decomposition reaction varies depending on the temperature, but is usually about 2 seconds to 10 hours, preferably about 5 seconds to 5 hours.

In addition, in the present invention, as mentioned above, the diazotization reaction is carried out at -100°C ~
It is carried out at 150°C, preferably about -80 to 100°C. Therefore, when the diazotization reaction is carried out at a temperature of 20°C or higher, the diazotization reaction and the thermal decomposition reaction proceed simultaneously (more precisely, according to a sequential reaction mechanism), but even in this case, overall, the objective p- which is a thing
Since fluorophenol is produced quantitatively, there is no problem.

The reaction solution thus obtained contains, in addition to the target product 2-fluorophenol, a small amount of unreacted raw materials, a by-product alkyl alcohol, and when an organic solvent is used in the diazotization reaction. Although organic solvents are contained, these can be easily isolated into their respective components by conventional separation procedures known per se, such as vacuum distillation, steam distillation, extraction, etc., thereby producing highly pure p-fluorinated Phenol is obtained. In addition, when an organic solvent is used during the diazotization reaction, it goes without saying that the organic solvent can be isolated by the above-mentioned separation operation and thus can be repeatedly reused.

In addition, the alkyl alcohol produced as a by-product during the diazotization reaction can also be isolated by the above separation procedure, so the isolated alkyl alcohol can be treated with sodium nitrite in the presence of a mineral acid such as sulfuric acid, hydrochloric acid, nitric acid, or phosphoric acid. If you react, the following (
3) Since it can be converted into alkyl nitrite again by the reaction shown in the formula, this can also be effectively reused.

ROH+ NaN0= + 1/281504-RON
O+ 1/2NaiSOn + HiO--・----
(3) In this regard, as in the conventional method using sodium nitrite as a diazotization agent, a large amount of solid sodium acid fluoride (NaHF, This is a serious problem with methods that cause various problems such as sticking.

〔Example〕

Hereinafter, the present invention will be explained in more detail with reference to Examples. In the following, % indicates weight %.

Examples 1-3 A Teflon reaction vessel with a capacity of 11 equipped with a stirrer, a reflux condenser and a thermometer was charged with p- Aminophenol, isoamyl nitrite as an alkyl nitrite, an aqueous hydrofluoric acid solution with a concentration shown in Table 1, and acetonitrile as an organic solvent in the amounts shown in Table 1 were charged, and then this mixed solution was heated while stirring. The diazotization reaction was carried out at a temperature of -10°C. After completion of the diazotization reaction,
The temperature of the reaction solution was further raised, and a thermal decomposition reaction was carried out at the temperature and time shown in Table 1.

The reaction in the present invention does not produce by-products such as solid acidic sodium fluoride as in conventional methods, so the operation is extremely smooth, and there are no problems such as stopping the reaction midway due to adhesion of solids. Ta.

After the completion of the thermal decomposition reaction, each reaction solution was rapidly cooled with ice water and neutralized with an aqueous sodium hydroxide solution.
Fluorophenol was eluted, and benzene was added thereto to extract p-fluorophenol. The extract was further distilled under reduced pressure to obtain p-fluorophenol. The amount and yield of P-fluorophenol (based on p-fluorophenol) are as shown in Table 1, and as a result of analysis by liquid chromatography, the purity was high at 99% by weight or more.

Examples 4 to 6 Using the reaction apparatus used in Examples 1 to 3, the diazotization reaction and thermal decomposition reaction of p-aminophenol were carried out in the same manner as in Examples 1 to 3 under the conditions shown in Table 1. .

After the completion of the thermal decomposition reaction, each reaction solution was rapidly cooled with ice water, neutralized with an aqueous sodium hydroxide solution, eluted with steam distillation, extracted with benzene, and the extract was distilled under reduced pressure in the same manner as in Examples 1 to 3. p-fluorophenol was obtained. The amount and yield of p-fluorophenol (based on p-fluorophenol) are shown in Table 1, and as a result of analysis by liquid chromatography, the purity was high at 99% by weight or more.

Incidentally, as in Examples 1 to 3, no trouble occurred during the diazotization reaction and thermal decomposition reaction.

Comparative Examples 1-2 Using the reaction apparatus used in Examples 1-3, the diazotization reaction and thermal decomposition reaction of p-amine phenol were carried out in the same manner as in Examples 1-3 under the conditions shown in Table 2. .

After the thermal decomposition reaction was completed, the same operations as in Examples 1 to 3 were performed to obtain p-fluorophenol. The amount and yield (based on p-fluorophenol) of p-fluorophenol were as shown in Table 2.

Table 2 [Effects of the Invention] As explained in detail above, the method for producing p-fluorophenol of the present invention uses p-aminophenol with an alkyl nitrite in the presence of an aqueous solution of hydrofluoric acid at a specific concentration. In this method, the diazonium salt produced is thermally decomposed.

Therefore, the conventional method of using sodium nitrite as a diazotizing agent has a low yield and produces a large amount of solid acidic sodium fluoride (Ha) IF g) as a by-product.
There was a problem that a1lFt could stick to the reaction vessel or stirrer, causing problems such as interfering with smooth reaction operation.
In contrast, the method of the present invention is as described above, so
As shown in the examples, the yield is as high as 40 to 60%, and a product of high purity can be obtained.

In addition, since the by-product is alkyl alcohol, there is no problem of it sticking to the reaction vessel.Furthermore, this by-product alkyl alcohol can be reacted with sodium nitrite in the presence of a mineral acid such as sulfuric acid. Another great advantage is that it can be reused as alkyl nitrite.

Incidentally, if the concentration of the hydrofluoric acid aqueous solution is outside the range specified by the present invention, the yield will decrease significantly as shown in Comparative Examples 1 and 2.

As described above, the method of the present invention makes it possible to safely produce high-purity p-fluorophenol on an industrial scale in high yield and has extremely large economic effects.

Patent applicant: Mitsui Toatsu Chemical Co., Ltd.

Claims (1)

[Claims] (1) A method for producing p-fluorophenol by reacting p-aminophenol with a diazotizing agent in the presence of hydrogen fluoride and thermally decomposing the resulting diazonium salt, comprising:
- A method for producing p-fluorophenol, which comprises carrying out a diazotization reaction of aminophenol using an alkyl nitrite in the presence of an aqueous solution of hydrofluoric acid having a concentration of 40 to 90% by weight.