JPS62238226A - Production of thermally stable fluorophenol or such - Google Patents

Abstract

PURPOSE:To obtain a thermally stable fluorophenol useful as an intermediate for drugs, agricultural chemicals, liquid crystal compounds, etc., by treating a crude fluorophenol with a reducing agent in production process or after production. CONSTITUTION:A fluorophenol shown by the formula (X1 and Z2 are H, Cl, F or Br and at least one is F; Y is H, Cl or Br; Z is amino or nitro when X1 is Cl, X2 is F and Y is H and Z is H in other cases) is treated with a reduc ing agent to stabilize the fluorophenol thermally. A metallic reducing agent, a H2 gas in the presence of a catalyst for hydrogenation, phosphine, phosphite, sulfide, etc., except reducing agents which can not be thermally used are used as the reducing agent and the amount of the reducing agent used is 0.5-30mol% based on the fluorophenol. Addition of protecting agent is further effective in order to protecting materials of reactor from the actions of a decomposition inhibitor (e.g. alkylamine) of the fluorophenol and hydrofluoric acid.

Description

DETAILED DESCRIPTION OF THE INVENTION "Industrial Field of Application" Fluorophenols, which are the object of the present invention, are important compounds as intermediates in the production of medicines, agricultural chemicals, liquid crystal compounds, and the like.

"Prior Art" Several methods are known for synthesizing fluorophenols, as described below.

For example, (1) JP-A-50-13342 (21 JP-A-50-36431) (3) JAC88194 (19
59) (41 USSR 154, 250 (1963)
(Known in 51 Japanese Unexamined Patent Publication No. 6O-193939, etc.).

However, when fluorophenols are industrially produced and the production process requires heating to 50'C or higher, it is not known that decomposition occurs. Further, there is no known means for preventing its decomposition.

1. Problems to be Solved by the Present Invention" The present inventors discovered that while performing inspection for producing fluorophenols on an industrial scale, reactions or, in particular, concentration, distillation, sublimation, and I was in disbelief at the extremely poor material balance during the refining of crystals, etc. Although the cause is not clear, it was also found that this effect is greatly amplified on an industrial scale.

As detailed experiments were carried out, it was discovered that the fluorophenols used for dyeing the χ of the present invention are common phenols, cresols,
It has been found that the decomposition upon heating is an order of magnitude greater than that of chlorophenol, etc.

"Means for Solving the Problems" The present invention provides a thermally stable fluorophenol which is characterized in that it is treated with a reducing agent during or after the production of the fluorophenol represented by the following general formula (1). This relates to a manufacturing method.

' (Xi, X2 is a hydrogen atom, a monoatomic atom, a bromine atom,
At least one of Xi + X2 is a fluorine atom Y: hydrogen atom, chlorine atom, bromine atom Z: When X is a chlorine atom, X2 is a fluorine atom, and Y is a hydrogen atom, an amine group, a nitro group , others are hydrogen atoms) The present inventors conducted trial and error with the understanding that the most important point when producing the present fluorophenols on an industrial scale is to suppress the above-mentioned decomposition during heating. As a result of stacking,
We have arrived at the present invention.

That is, the gist of the present invention is the general formula (1)
The method is to prevent thermal decomposition of fluorophenols by treating them with a reducing agent shown in the following.

Thermal decomposition is more likely to occur with impure 70-lophenols, and the resulting thermal decomposition products contain many polymeric substances that have undergone dehydrohalogenation. The method of treatment with a reducing agent was discovered by chance, and its theoretical basis in relation to thermal decomposition products has not yet been sufficiently clarified. There has never been a case where something like this has been reported. However, it currently seems reasonable to believe that removing trace amounts of triggering impurities contained in fluorophenols through reduction helps prevent decomposition. It is thought that this impurity is something that is very easily reduced, such as an oxidized intermediate.

The treatment with a reducing agent [1υ] may be performed during the production process of the crude fluorophenols or after the production. An example of this is a method in which a reducing agent is added during steam distillation of a diazonium salt of fluoroaniline to obtain thermally stable fluorophenol. Post-manufacturing processing is
There is a method of normally treating crude fluorophenols with a reducing agent, or a method of adding (presence of) a reducing agent to the system during a process where thermal decomposition is a problem (for example, a process of heating above 50°C). .

For treatment with a reducing agent, it is usually sufficient to simply add it, but it is also possible to select the optimal conditions depending on the type of reducing agent.The guidelines for this can be found in "Oxidation and Reduction of Organic Compounds" by Yoshibe Ogata, published by Nankodo.
is described in detail.

As the reducing agent of the present invention, all commonly used reducing agents can be used. However, I, thermal LiAlH4,Na
Alkali metal hydrides such as BFL, hydrazine,
These include strong alkaline reducing agents such as sodium thiosulfate, sodium sulfite, and hydrosulfide, iron powder, iron compounds such as ferric chloride, and copper compounds such as copper powder and cupric chloride.

The reason these cannot be used when heated is that they act as accelerators for decomposition by another mechanism, so they must be removed from the outside of the system after reduction treatment at room temperature or lower, or they must be removed from the system using strong alkaline i
If the base agent is neutralized with an acid, it will have a sufficient effect of preventing decomposition even if a heating operation is performed afterwards.

Examples of reducing agents other than these that can be used in the present invention include metal reducing agents such as metal aluminum, metal zinc, metal tin, and expanded Raney nickel, and hydrogenation catalysts (palladium-carbon expanded Raney nickel, etc.) in the coexistence. hydrogen scum, phosphines such as triphenylphosphine, tritolylphosphine, tri-11-7' tylphosphine, 5
Metal hydrides such as nI42.5nl-1, phosphites such as trimethyl phosphite and triethyl phosphite, sulfides such as hydrogen sulfide, nickel sulfide and zinc sulfide, acidic sulfites such as acidic sodium sulfate, Examples include side phosphates such as potassium diphosphate, and sacrificial phosphates such as potassium hypophosphite. The amount used is preferably 0.5% to 30'% of the mole of the fluorophenol, particularly preferably 1 to 15%.

The stable fluorophenols obtained according to the present invention are particularly effective in concentration, distillation, recrystallization, and recrystallization.

Also, considering operability, efficacy, sustainability, etc., citronorolophenols f? F: It is industrially more advantageous to add a reducing agent into the heat treatment system such as concentrated distillation. It is even more effective when a protective agent is used to protect the reactor material from the action of hydrogen acid.

Examples of the decomposition inhibitor include amines such as argylamines, aromatic amines, and heterocyclic amines, and thi'ols such as aliphatic thiols and aromatic thiols.

As a protective agent for protecting the reactor material from the action of hydrofluoric acid, 13. 7. Group 1 A metals such as At or compounds thereof; Group 1 B metals such as Ti and Zr or compounds thereof; alkaline earth metals or compounds thereof; n,
Examples include Ni metal or compound.

"Example" This will be explained in detail in the following examples.

Example 1゜ 150g of P-fluoroaniline and 150g of concentrated sulfuric acid.

water. 91.2 g of sodium nitrite in 650 g of water
was diazotized as an aqueous solution of 40%. During diazotization, the temperature was maintained at 5°C while adding 800 g of ice. Copper sulfate 5
100-120 g into a bath containing 225 g of water and 225 g of water.
It was added dropwise at °C, and the diazonium salt was decomposed while steam distilling the generated P-fluorophenol. The obtained P-fluorophenol was added to 600% of toluene from water.
m1. After extraction 1-, a toluene solution was obtained. There were 113.2 g of P-fluorophenol in this.

To this, 60 ml of water, 5uCl・21 (2016g
, @20 g of hydrochloric acid was added, and the mixture was stirred vigorously at room temperature overnight.

After separating the toluene layer and washing with dilute brine, P-fluorophenol was extracted using a gas chromatograph at a constant f&l-
It contained 1.09.4g.

This was heated under reduced pressure at 150WHg, 70° (:, 12hr
Concentrate with ca 30 ml II Hg 100-1
Distillation was carried out for 20 hours at 30°C (pot internal temperature). A total of 99° IgP-fluorophenol was obtained from the first distillate, main distillate, and 1-fluorophenol.

The P-fluorophenol in the hold-up in the distillation column and the P-fluorophenol in the bottoms are 2.2 g and 4.8 g, respectively, and the mass balance for P-fluorophenol during concentration and distillation is 97 .0% was confirmed.

Comparative Example 1 In exactly the same manner as in Example 14, a toluene solution of P-fluorophenol was obtained. The P-fluorophenol contained therein was 113.3 g. This was concentrated and distilled under the same conditions as in Example 1.0 without any reduction treatment. A total of 94.4 g of P-fluorophenol was obtained from the first distillate and main distillate, and 2.
It was found that 5.9 g of I)-fluorophenol was contained in the residue. The product balance for I)-fluorophenol in the concentration and distillation steps without reduction treatment was 90.8%. Example 1. Compared to ■)-17g lower F17 in the initial distillation and main distillation of fluorophenol, the effect of reduction treatment is clear, but if you look at the mass balance in the concentration and distillation process,
Furthermore, the effect is clear.

Example 2 300 g of P-fluorophenol, 2 tons of water, and 120 g of sodium hydroxide are placed in a four-eye flask in sequence. 20'C
The temperature was adjusted to 15.51 w/w, and 1.381 w/w of Hirosho sodium chlorate was added in about 3 hours. Thereafter, the reaction solution is neutralized with hydrochloric acid until it becomes neutral. Furthermore, it was extracted twice with 500 g of 1,2-dichloroethane. As a result, 284 g of 2-chloro-4-fluorophenol and 52 g of 2-6-cyclo-4-fluorophenol.

A composition containing 20 g of raw material was obtained. 10 g of triphenylphosphine was added to this and rectified at 73°C at 126 liters for 24 hours. 267 g of the main distillate, initial distillate, hold-up, and bottom residue were analyzed to find 12 g of 2-chloro-4-fluorophenol (1ζ). is.

The material balance was 982 cm.

Example: 3° Comparative Example 1. A toluene solution of 1)-fluorophenol after the completion of diazolysis using iG was prepared, and the solution was treated under the same conditions as in Comparative Example 1 until the concentration of 1)-fluorophenol was 79.3%. It was concentrated until

20 g of this concentrated liquid was placed in a Deflon container, various reducing agents were added thereto, and the mixture was heated at 1500C for 20 hours. The p-fluorophenol remaining after the treatment was quantified by gas chromatography, and the residual rate was calculated.

The results are shown in the table in comparison with the case without additives.

Examples 9 to 14 Using the same experimental methods as Examples 3 to 8, a fluorophenol decomposition inhibitor and some protective agents to protect the reactor material from the action of hydrofluoric acid were combined to produce P- The residual rate of fluorophenol was determined to be 1111.

In addition, in Example 9.11.13.1.4, glass (
Slide glass for blood microscope) 5tJS, 304.5U
A test piece of S316 was put in, but no corrosion was observed in any of them.

Example 15゜Actual IA Example 1. Same as <I) - A toluene solution of fluorophenol is fG.

The P-fluorophenol contained in this is 112.8
It was g.

3.4 g of triphenylphosphine was added thereto, and Example 1. Concentration and distillation were carried out under the same conditions as above. A combination of the first distillate and the main fraction yielded 103.6 g L:1) P-fluorophenol.

The yield of the concentration and distillation process was 91.8%.

P-fluorophenol in the hold-up in the tower, 2
．． 5g, ffi remaining P-70 Rofeno // &t
The mass balance for P-fluorophenol was 98.1%.

"Effects of the Invention" According to the present invention, it has become possible to suppress the decomposition of fluorophenols during heating, and it has become possible to improve the yield.

Claims (1)

[Claims] (1) Process for producing thermally stable fluorophenols, characterized by treatment with a reducing agent during or after the production of crude fluorophenols represented by the following general formula (I) ) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (X_1 and X_2 are hydrogen atoms, chlorine atoms, fluorine atoms,
Represents a bromine atom. However, at least one of X_1 and X_2 is a fluorine atom. Y represents a hydrogen atom, a chlorine atom, or a bromine atom, and in Z, X_1 represents a chlorine atom and X_2 represents a fluorine atom. However, when Y is a hydrogen atom, it represents an amino group, a nitro group, and the others represent a hydrogen atom. )