JPH02154A - Production of 3,4,6-trifluorophthalonitrile - Google Patents

Abstract

PURPOSE:To obtain a compound useful as a synthetic intermediate for medicines, agricultural chemicals, industrial chemicals, etc., in high purity and yield for a short time by reacting tetrafluorophthalonitrile with a solid metal or alloy. CONSTITUTION:Tetrafluorophthalonitrile is reacted with a solid metal, such as metallic zinc, or solid alloy (e.g. zinc amalgam) in water or a mixed solvent thereof and an organic solvent (e.g. ethyl ether) at >=20 deg.C temperature to afford the objective substance. The solid metal or alloy is used in an amount of 0.8-10mol, preferably 1-2mol based on 1mol tetrafluorophthalonitrile. The reaction may be also carried out in the presence of an acid (e.g. sulfuric acid) or by using a water-soluble salt.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a method for producing 3,4,6-1-lifluorophthalonitrile, which is extremely useful as an intermediate for pharmaceuticals, agricultural chemicals, industrial drugs, etc. Specifically, the present invention relates to a method for producing 3,4°6-trifluorophthalonitrile, which comprises reacting tetrafluorophthalonitrile with a solid metal or solid alloy in an aqueous solvent.

[Conventional technology]

3.4. As far as the present inventor knows, there is almost no literature regarding a method for industrially synthesizing 6-1-lifluorophthalonitrile. The only “J, Chem, Soe”
.

Perkin II” Volume 12 No. 1288-129
On page 2 (1978 edition), “J, Org, Chem
, ``According to the method described in Vol. 31, p. 746 (1966 edition), 4-hydrazino-3,4,6-trifluorophthalonitrile was obtained from tetrafluorophthalonitrile, and then this was reacted with cupric sulfate. The preparation of 3,4.6 trifluorophthalonitrile is described.

The method described in "J, Org, Chem," Vol. 4 shif/-
2,3,5,6-titrafluorophenylhydrazine was reacted with an aqueous copper sulfate solution under heating to form 2,3°5.6-
Titrafluorobenzonitrile is obtained.

Therefore “J, Chem, Soc, Perkin
The method for synthesizing 3,4.6-trifluorophthalonitrile in Volume 12 of "If" is considered to follow the following formula.

However, this method requires a long process, and
As stated in this document, due to the low yield,
It is difficult to say that this method is sufficient in terms of industrial implementation.

[Problem that the invention seeks to solve]

The present inventors have solved the problems of the long process and insufficient reaction yield of the prior art (as a result of intensive research, we have found that tetrafluorophthalonitrile (hereinafter F, P
By simply heating N (sometimes abbreviated as N) in an aqueous solvent together with a solid metal ring such as metallic zinc, it can be defluorinated and reduced extremely easily and in a short time, resulting in highly pure 3.4.6-
The present invention was completed by discovering that trifluorophthalonitrile (hereinafter sometimes abbreviated as F or PN) can be produced in high yield.

[Means for solving the problem] The present invention provides a 3,4゜6-trifluorocarbon compound, characterized in that tetrafluorophthalonitrile is reacted with a solid metal or solid alloy, preferably metal zinc, in an aqueous solvent. The object of the present invention is to provide a method for producing fluorophthalonitrile.

The present invention will be explained in detail below.

The aqueous solvent used in the present invention refers to water or a mixed solvent of water and a water-soluble organic solvent, and by using such an organic solvent in combination, the solid phase and/or oil phase can be mixed into the aqueous phase. In some cases, they can be dissolved to form a single liquid phase, and when the reaction according to the present invention is carried out under reflux temperature conditions as described later, it is also possible to adjust the reflux temperature.

As such an organic solvent, any organic solvent that dissolves 50 parts by weight or more in 100 parts by weight of water can be used without any particular restriction, such as methyl alcohol, ethyl alcohol, propyl alcohol (n, -, i,), etc. Aliphatic alcohols having 1 to 3 carbon atoms; for example, other monohydric alcohols such as allyl alcohol and furfuryl alcohol; for example, ethylene glycol, propylene glycol (1,2-, 1,3-), glycerin Aliphatic polyhydric alcohols having 1 to 3 carbon atoms, such as polyethylene glycol that is liquid at room temperature; such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether,
Mono- or dietherified products of ethylene glycol and aliphatic alcohols having 1 to 4 carbon atoms, such as ethylene glycol dimethyl ether; for example, diethylene glycol dimethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, etc. A mono- or dietherified product of diethylene glycol and an aliphatic alcohol having 1 to 4 carbon atoms; For example, a monoetherified product of glycerin and an aliphatic alcohol having 1 to 3 carbon atoms, such as 1-glycerin monomethyl ether. ; For example, tetrahydrofuran, dioxane (1,3-, 1,4-)
and other water-soluble organic solvents such as acetone, acetonitrile, lactonitrile, N,N-dimethylformamide, dimethyl sulfoxide, and diethyl sulfoxide.

These organic solvents can be used alone or in a mixture of two or more. Among these organic solvents, aliphatic alcohols are particularly preferred from the viewpoint of availability and economy.

The present invention provides F4. The present invention relates to a method for producing F3PN, which is characterized by reacting PN with a solid metal or solid alloy (hereinafter sometimes abbreviated as solid metal, etc.) in an aqueous solvent.

Examples of the solid metals include zinc, tin, iron, nickel, chromium, aluminum, copper, etc., and examples of the solid alloys include metal amalgams such as zinc amalgam, tin amalgam, and aluminum amalgam; For example, other metal alloys such as brass, bronze, aluminum-nickel alloy, aluminum-lead alloy, etc. can be mentioned. Among these, it is preferable to use solid metals from the viewpoint of easy availability and good reaction yield, and it is particularly preferable to use metallic zinc.

As the above-mentioned metal zinc, any commercially available metal zinc powder or the like can be used. As shown in the reaction formula below, the amount of metallic zinc to be used is theoretically 1 mole per 1 mole of F, PN, but usually 0.8 to 10
mol, preferably 0.9 to 5 mol, particularly preferably 1
It is preferable to make it exist in an amount of ~2 mol. By using metallic zinc at or above the lower limit of the above usage range, the reaction rate can be increased, and by using at least the lower limit,
By-product 3,6-cyfluorophthalonitrile (hereinafter referred to as F2P) resulting from further defluorination reduction reaction of the generated F3PN
(sometimes abbreviated as N) can be suppressed to a very small amount or less, so it is preferable to use an amount within the above usage range.

The reaction formula when zinc is used as the solid metal is considered to be as follows.

The above reaction according to the present invention proceeds regardless of whether the aqueous solvent in the reaction system is in the neutral, acidic or alkaline range. For example, in the alkaline range of 9119 or higher, the 5-position 3, 4 in which fluorine is substituted with a hydroxyl group
．． 6-) Lifluoro-5-hydroxyphthalonitrile, phthalocyanine compounds resulting from addition reactions between nitrile groups, and tetrafluorophthalamide resulting from hydrolysis of nitrile groups may be produced as by-products.
Less than H9, number 4 is p)12-7, especially pFI3-
Preferably, the reaction is carried out in an aqueous solvent in the range of 6.

The reaction in the method of the invention can be carried out in the presence of an acid. Examples of acids that can be used in the present invention include inorganic acids such as sulfuric acid, hydrochloric acid, and nitric acid; and organic acids such as acetic acid, oxalic acid, benzoic acid, phthalic anhydride, p-)luenesulfonic acid, etc. Anything that exhibits acidity can be used. Among these acids, inorganic acids such as sulfuric acid, hydrochloric acid, and nitric acid are preferably used for reasons such as ease of availability.

However, for example, when using zinc, which is most suitable as a solid metal, if the reaction system is in a strongly acidic region, a side reaction between the acid and metal zinc (hydrogen is generated and the acid becomes fluorophthalimide, 3.4.6 -) Rifluorophthalimide, tetrafluorophthalic acid, 3.4.6-trifluorophthalic acid, etc., and mixtures thereof may be produced as by-products. For these reasons, the amount of acid used is preferably 0 to 5 equivalents, particularly 0.1 to 5 equivalents per mole of raw material F4PN, and the amount (number of moles) of the metal zinc used is X
It is preferable to use an amount in a range that satisfies the relational expression 1≦2x−y≦3, where y is the amount of acid (number of equivalents).

Furthermore, the acid concentration in the reaction is ff11000g of the aqueous solvent.
It is preferable to use it in a range of 10 equivalents or less, and 8
It is more preferable to use the amount within the equivalent range. As for the method of adding the acid, in addition to the method of adding the acid all at once at the beginning of the reaction, the method of adding the acid sequentially can also be selected as appropriate.

Zinc and acid may react to liberate corrosive hydrogen fluoride. Furthermore, if the concentration of acid is too excessive, the nitrile group undergoes hydrolysis, resulting in a tetraph, i.e. pH below 9.
Furthermore, the reaction can be carried out in a reaction system having a pH in the range of 2 to 7. According to this method, relatively inexpensive stainless steel such as 5IJS304.5US316 can be used during industrialization, and the target compound can be obtained with the same high purity and high yield as when using acids. It has an excellent effect of being able to

Such water-soluble salts are not particularly limited, and any salt can be used as long as it dissolves at least 0.101 g, preferably at least 1 g, in 100 g of water.

Such water-soluble salts include, for example, sulfates such as ammonium sulfate, sodium sulfate, sodium hydrogen sulfate, potassium sulfate, and potassium hydrogen sulfate; for example, ammonium chloride, sodium chloride, mu, potassium chloride, calcium chloride, magnesium chloride, Hydrochlorides such as barium chloride; For example, nitrates such as ammonium nitrate, sodium nitrate, potassium nitrate, calcium nitrate, magnesium nitrate; For example, ammonium phosphate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate, sodium phosphate,
Phosphates such as sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate; borates such as sodium tetraborate; for example, ammonium citrate , citrates such as ammonium hydrogen taunate, sodium citrate, sodium hydrogen citrate, potassium citrate, potassium hydrogen citrate; acetates such as ammonium acetate, sodium acetate, potassium acetate, calcium acetate; for example, tartaric acid; Tartarates such as sodium, sodium hydrogen tartrate, potassium tartrate, potassium hydrogen tartrate; for example,
Oxalates such as potassium oxalate; For example, lactates such as sodium lactate and calcium lactate; Ammonium phthalate, Ammonium hydrogen phthalate, Sodium phthalate,
Phthalate salts such as sodium hydrogen phthalate, potassium phthalate, potassium hydrogen phthalate; strong acid weak base salts such as ammonium sulfate, ammonium hydrochloride, ammonium nitrate, etc.; sodium hydrogen sulfate, potassium hydrogen sulfate, sodium phosphate-hydrogen, phosphorus; Sodium dihydrogen acid, phosphoric acid-
Strong base hydrogen salts of inorganic acids such as potassium hydrogen and potassium dihydrogen phosphate; ammonium hydrogen citrate, sodium hydrogen citrate, potassium hydrogen citrate, sodium hydrogen tartrate, potassium hydrogen tartrate, sodium hydrogen phthalate, potassium hydrogen phthalate If necessary, a base such as sodium hydroxide, potassium hydroxide, or ammonia may be used in combination to adjust the pH of the aqueous solvent to the above-mentioned suitable pH range. You can also.

Furthermore, by using the above-mentioned salts in combination with an appropriate acid, the pH of the aqueous solvent of the reaction system can be adjusted to the above-mentioned preferred range of 9. Such salts include sodium sulfate, potassium sulfate, sodium chloride, potassium chloride,
Strong acids and strong bases whose aqueous solutions are almost neutral, such as calcium chloride, magnesium chloride, barium chloride, sodium nitrate, and potassium nitrate; inorganic acids whose aqueous solutions are alkaline, such as sodium phosphate, potassium phosphate, and sodium tetraborate. Strong base normal salt; sodium citrate, potassium citrate, sodium acetate, potassium acetate, calcium acetate,
Sodium tartrate, potassium tartrate, sodium lactate,
Examples include organic acid strong base normal salts whose aqueous solutions are alkaline, such as calcium lactate, sodium phthalate, and potassium phthalate.

Acids suitable for combination with the above salts include, for example, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid; for example, citric acid, acetic acid, succinic acid, tartaric acid, oxalic acid,
Examples include organic acids such as lactic acid, phthalic acid, benzoic acid, and p-toluenesulfonic acid.

The amount of the water-soluble salt used is not particularly limited, but it is preferable to use an amount such that the pu of the reaction system falls within the above range, and the total amount is, for example, 0.01 to 1.0 mol, the concentration is, for example, 0.01 to 2.0 mol in total, particularly 0.02 to 2.0 mol.
A 1.0 molar layer is preferable.

The reaction in the method of the present invention can generally be carried out at a temperature of 20°C or higher, preferably 50°C or higher from the viewpoint of reaction rate, and it is also possible to carry out the reaction at high temperature and high pressure in a closed pressure-resistant reaction tank. be. However, from the viewpoint of reaction equipment cost, etc., it is preferable to carry out the reaction under atmospheric pressure and at a temperature in the range of 50° C. to reflux temperature. Further, from the viewpoint of reactivity, in a reaction system where the reflux temperature is 100°C or higher, it is more preferable to carry out the reaction at a temperature in the range of 80°C to refluxing temperature.

The reaction time is not particularly limited, but if it is too long, the side reaction of F2PN production may proceed, so it is generally carried out for about 15 minutes to 10 hours, preferably about 30 minutes to 6 hours. It's good.

Furthermore, although the reaction in the method of the present invention proceeds easily in an aqueous solvent, the starting material FtPN has a melting point of 8.
It is a water-insoluble solid with a temperature of 6 to 87°C, and the target substances P and PN are hydrophobic solids with a melting point of 36.5 to 37.5°C. A solid phase (a solid consisting of a starting material and a target substance, and a solid metal such as zinc metal, etc.), or two liquid phases, an aqueous phase and an oil phase, and a solid phase (a solid metal, etc.). This is a heterophasic reaction, and therefore it is best to carry out this reaction while keeping the reaction system as homogeneous as possible by stirring.

After the completion of the reaction, the solid matter is separated by means such as steam distillation or filtration, and the organic layer is extracted using an extraction solvent such as ether, chloroform, etc., and the solvent is distilled off.
．． 6-trifluorophthalonitrile can be obtained.

Moreover, if necessary, the obtained product can be further purified by means such as distillation.

〔Example〕

Hereinafter, the present invention will be explained in more detail with reference to Examples.

Example 1 300m6 flask equipped with cooling reflux tube and thermometer, F
4PN42 g (purity 96% ffi, 0.20-E
), 15 g of powdered zinc (purity 96% by weight, 0.22 mol) and 125 g of water, and while stirring, 6.2 g of sulfuric acid was added.
(purity 98% by weight, 0.062 gram equivalent) and 1
The reaction was carried out at 00°C for 2 hours. The pH values at the start and end of the reaction were 0.6 and 4.1, respectively.

After the reaction was completed, the mixture was cooled, 60g-a of ethyl ether was added, and the solids were separated by filtration.The solids were washed with ethyl ether, and the resulting mixture of the liquid and the ether washing liquid was separated. The ether layer is isolated by
It was analyzed using internal standard method using liquid chromatography.

The reaction conditions and analysis results are shown in Table 1.

Examples 2 to 5 Reactions and analyzes were carried out in the same manner as in Example 1 except that the amount of sulfuric acid used and the sulfuric acid concentration were changed. The reaction conditions and analysis results are shown in Table 1.

Example 6 Reaction and analysis were carried out in the same manner as in Example 1 except that the amounts of water and sulfuric acid used were changed. The reaction conditions and analysis results are shown in Table 1.

Example 7 In Example 1, the reaction and analysis were carried out in the same manner as in Example 1 except that the reaction temperature and reaction time were changed. The reaction conditions and analysis results are shown in Table 1.

Examples 8 to 10 Reactions and analyzes were carried out in the same manner as in Example 1 except that the amounts of zinc and sulfuric acid used were changed and the sulfuric acid concentration was changed. The reaction conditions and analysis results are shown in Table 1.

Examples 11 and 12 Reactions and analyzes were carried out in the same manner as in Example 1 except that hydrochloric acid and acetic acid were used instead of sulfuric acid.

The reaction conditions and analysis results are shown in Table 1.

Example 13 The reaction and analysis were carried out in the same manner as in Example 1 except that a 50% by weight aqueous ethanol solution was used instead of water. The reaction conditions and analysis results are shown in Table 1.

Example 14 Reaction and analysis were carried out in the same manner except that 98% by weight, 0.02 mol) was used and the reaction time was changed to 2 hours. The reaction conditions and analysis results are shown in Table 2.

Examples 15 to 19 In Example 14, the reaction was carried out in the same manner as in Example 14, except that the type and amount of water-soluble salt used were changed and the reaction temperature was set to 95°C. Hereinafter, analysis was carried out in the same manner as in Example 1. I did it. The reaction conditions and analysis results are shown in Table 2.

O Example ≠ The reaction was carried out in the same manner as in Example 1, the reaction product was treated in the same manner as in Example 1, and the ether layer obtained by separating the mixture from the furnace liquid and the ether cleaning liquid was added to magnesium sulfate. It was dried. After completion of drying, magnesium sulfate was filtered and ether was distilled off.

Purity 9 is obtained by distilling the residue after ether distillation under reduced pressure.
32.7 g of 8.0% by weight trifluorophthalonitrile
(yield: 88.0 mol%).

In addition, the obtained bird The analysis values are as follows mass spectrum EI　M/e=182 infrared spectrum 2250cm-' 3090cm-' 19F-NMR Quality; CFICOOH): δ=-'26.0ppm fluorophthalonitrile Met.

(C=N) (C-H) (Solvent; CDCNz 1H-decoupling (IF, d-d 41.3ppm (IF.

53.2ppm (IF, (Mゝ , internal standard ng , J=9.2H21 13,4Hz) J=9.2Hz 20.8Hz) -J = 13.4) 1z 20.8Hz d-d.

d-d.

Claims (1)

[Claims] (1) A method for producing 3,4,6-trifluorophthalonitrile, which comprises reacting tetrafluorophthalonitrile with a solid metal or solid alloy in an aqueous solvent.