RU2343142C2 - Method of obtaining pentafluorophenol - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: method of obtaining pentafluorophenol can be used for obtaining medications, fluoridated monomers and reagents for peptide synthesis by reaction of hexafluorobenzol with water solutions of alkali and earth alkali metal hydroxides. Process is carried out in presence of catalyst of interphase transfer at temperature 100-140°C. As a rule, as catalysts of interphase transfer, chlorides or bromides of tetrakis(dialkylamido)phosphonium, or N,N',N" - hexa-alkyl-substituted guanidinium, or their mixtures are used, and catalyst of interphase transfer is used in concentration from 0.5 to 1 wt % of initial hexafluorobenzol amount. Usually 2.05-2.35 equivalent of alkali reagent with respect to hexafluorobenzol is used in form of 20-30% water solution.

EFFECT: obtaining pentafluorophenol with high purity degree and simplification of its synthesis technology.

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Description

The invention relates to the field of chemical technology for the preparation of derivatives of fluoroaromatic compounds, namely pentafluorophenol C ₆ F ₅ OH. The specified compound is used to obtain drugs, fluorinated monomers and reagents for peptide synthesis. One of the main conditions for the practical use of pentafluorophenol is to obtain this compound of high purity.

State of the art

A known method of producing pentafluorophenol by decomposition of pentafluorophenylalkyl ethers; the latter are obtained by the reaction of the corresponding alcoholates with hexafluorobenzene (72% yield for pentafluoroanisole). Decomposition is carried out by acids or aluminum chloride, the yield of pentafluorophenol is 20-58% (E. Forbes, R. Richardson, M. Stasey, J. Tatlow, J. Chem. Soc., June, p.2019-2021, 1959).

Signs that are common to the known and claimed method are to use hexafluorobenzene available in industrial quantities as a starting compound.

The reason that prevents obtaining the required technical result in the known method is the use of a two-stage scheme for producing pentafluorophenol from hexafluorobenzene. Another reason is the low overall yield of the target product. In addition, the pentafluorophenol thus obtained requires additional purification from impurities due to the incomplete conversion of the decomposition of pentafluorophenylalkyl ethers and the formation of by-products.

A known method of producing pentafluorophenol directly from hexafluorobenzene and potassium hydroxide in an organic solvent. In tert-butanol, the yield of pentafluorophenol reaches 71% (J. M. Birchall, R. N. Haszeldine, J. Chem. Soc., Jan., p. 13-17, 1959). In anhydrous pyridine, the yield of pentafluorophenol is 52% (W. Pummer, L. Wall, Science, 127, p. 643, 1958).

Signs that are common to the known and claimed method are to use potassium hydroxide and hexafluorobenzene available in industrial quantities as starting compounds.

The reason that impedes obtaining the required technical result in the known method is the need to use organic solvents and their subsequent regeneration, which significantly limits the industrial implementation of these methods. Another significant limitation of these methods is the low yield and low quality of the target product. So, pentafluorophenol obtained in tert-butanol has a melting point of only 25-30 ° C instead of the required 34-36 ° C and requires additional purification from traces of solvents and by-products.

The closest analogue (prototype) is a method for producing pentafluorophenol by reacting hexafluorobenzene with a concentrated aqueous solution of potassium hydroxide in an autoclave with stirring and a temperature of 175 ° C in 83.5% yield (L.Wall, W.Pummer, J.Fearn, J. Antonucci, J. Rcs. NBS, 67A, p. 481-497, 1963).

Signs that are common to the known and claimed method are to use potassium hydroxide and hexafluorobenzene available in industrial quantities as starting compounds.

The reason that impedes obtaining the required technical result in the known method is the necessity of carrying out the reaction at high pressure (above 15 atm.), Which significantly limits the industrial implementation of this method. In addition, carrying out the process at high temperature leads to the formation of undesirable by-products of further substitution of fluorine atoms in the aromatic ring of tetrafluororesorcinol and tetrafluorohydroquinone.

SUMMARY OF THE INVENTION

The problem to which the invention is directed, is to improve the technology for producing high purity pentafluorophenol by overcoming the disadvantages of known methods.

The technical result that determines the solution of the problem is that the synthesis of pentafluorophenol occurs under mild conditions that allow the use of serial equipment and do not lead to the formation of by-products.

The technical result is achieved by carrying out the reaction of hexafluorobenzene with aqueous solutions of hydroxides of alkali or alkaline-earth metals in the presence of a phase transfer catalyst at a temperature of 100-140 ° C.

The phase transfer catalysts in the reaction of hexafluorobenzene with alkalis are preferably taken in amounts of from 0.5 to 10 weight percent relative to the amount of the starting hexafluorobenzene, preferably 2-5%.

In the inventive method, the chlorides and bromides of tetrakis (dialkylamino) phosphonium, or N, N ', N ”-hexaalkyl-substituted guanidinium, or mixtures thereof are preferably used as phase transfer catalysts.

For the implementation of the reaction, preferably aqueous solutions of alkali metal hydroxides are used, taken in a slight excess against stoichiometry, most often 2.05-2.35 equivalents of an alkaline reagent are used with respect to hexafluorobenzene. More often used 20-30% aqueous solutions.

New (relative to the prototype) features of the claimed method are the reaction of hexafluorobenzene with alkali metal hydroxides in the presence of phase transfer catalysts at elevated temperatures.

Industrial applicability

The synthesis of pentafluorophenol in the presence of phase transfer catalysts can significantly reduce the temperature of the process and, accordingly, reduce the excess pressure in the reactor to the operating pressure of standard industrial devices. In addition, the use of phase transfer catalysts that are stable at temperatures of 100-140 ° C, allows to reduce the number of by-products formed and increase the yield of the target product.

The most commonly used chlorides and bromides are tetrakis (dialkylamido) phosphonium and N, N ', N ”-hexaalkyl substituted guanidinium, which are quite accessible and highly stable in concentrated aqueous solutions of alkalis at elevated temperatures and are highly effective in nucleophilic substitution of fluorine atoms in the aromatic ring . The use of iodides is possible, but irrational because of their high cost.

The reaction of hexafluorobenzene with alkali or alkaline earth metal hydroxides in the presence of phase transfer catalysts is carried out under stirring and heating in a typical pressure reactor.

The amount of catalyst in the reaction is from 0.5 to 10% by weight relative to hexafluorobenzene, preferably 2-5%. The use of small concentrations of the catalyst leads to a slowdown of the reaction and a decrease in the yield of the target products, and an increase in its amount over 10% is not economically feasible.

Sodium and potassium hydroxides are used as the alkaline agent, and calcium hydroxide as the alkaline-earth agent. Hydroxides of lithium, rubidium, cesium and strontium are expensive for widespread use.

The amount of hydroxide is determined by the stoichiometry of the reaction and is usually taken with an excess of not more than 35% by stoichiometric.

The reaction temperature is selected based on the hardware design. The use of high temperatures above 140 ° C will lead to the formation of high pressures, and temperatures below 100 ° C will greatly slow down the reaction and will not give a complete conversion of the reactants. The optimal range can be considered as 100-140 ° C, more preferably 120-130 ° C, while the pressure in the reactor does not exceed 5 atmospheres.

Embodiments of the invention

The following examples confirm the possibility of implementing the method for producing pentafluorophenol according to the invention, but do not exhaust it.

Example No. 1 (comparison experience with the prototype without the use of a catalyst).

In a 2.5 liter steel reactor for pressure purposes, equipped with a stirrer, 930 g (5.0 mol) of hexafluorobenzene and a solution of 440 g (11.0 mol) of NaOH in 1000 ml of water are placed. The reaction mass is heated with stirring to 125 ° C for 48 hours, while the pressure reaches 4.5 atm. Then, unreacted hexafluorobenzene is distilled off from the reactor. 874 g of unreacted hexafluorobenzene were isolated; the conversion according to the starting reagent was 6%.

Example No. 2.

In a 2.5 liter steel reactor for pressure purposes, equipped with a stirrer, 930 g (5.0 mol) of hexafluorobenzene (basic substance content 99.7%), a solution of 440 g (11.0 mol) NaOH in 1000 ml of water are placed and 30 g (7.5 mmol) of tetrakis (diethylamido) phosphonium bromide. The reaction mass is heated with stirring to 125 ° C for 12 hours, while the pressure drops from 4.5 atm. up to 2.2 atm., and the conversion of hexafluorobenzene reaches 100%. Then the reaction mass is cooled, filtered from sodium fluoride, the filtrate is acidified with sulfuric acid. The organic layer containing pentafluorophenol and up to 20% water is rectified. Received 846 g of pentafluorophenol with so Kip. 142-143 ° C, mp 35-36 ° C and a basic substance content of 99.4% (water content of 0.4%). Yield 92%.

Example No. 3.

In a 2.5 L steel reactor for pressure purposes, equipped with a stirrer, 930 g (5.0 mol) of hexafluorobenzene (basic substance content 99.7%), a solution of 220 g (5.5 mol) NaOH in 1000 ml of H are placed ₂ O, 203.5 (2.75 mol) of Ca (OH) ₂ and 30 g (7.5 mmol) of tetrakis (diethylamido) phosphonium bromide are added. The reaction mass is heated with stirring to 125 ° C for 12 hours, while the pressure drops from 4.5 atm. up to 2.2 atm., and the conversion of hexafluorobenzene reaches 100%. Then the reaction mass is cooled, filtered from calcium fluoride, the filtrate is acidified with sulfuric acid. The organic layer containing pentafluorophenol and 20% water is rectified. Received 853 g of pentafluorophenol with so Kip. 142-143 ° C, mp 35-36 ° C and a basic substance content of 99.3% (water content of 0.4%). Yield 92.7%.

Example 4

930 g (5.0 mol) of hexafluorobenzene (99.7% of the basic substance), 1540 g of a 40% aqueous potassium hydroxide solution (11.0 mol) are placed in a 2.5 L steel reactor for pressure purposes, equipped with a stirrer. and 25 g (8.1 mmol) of N, N ', N ”-hexaethyl substituted guanidinium bromide. The reaction mass is heated with stirring to 130 ° C for 16 hours, while the pressure drops from 4.9 atm. up to 2.2 atm., and the conversion of hexafluorobenzene reaches 100%. Then the reaction mass is cooled, the precipitated potassium pentafluorophenolate is filtered, to which 2 L of 40% sulfuric acid is added. The organic layer is separated and dried by azeotropic distillation of water, the resulting pentafluorophenol is rectified. 819 g of pentafluorophenol with boiling point are isolated. 142-143 ° C, mp 35-36 ° C and a basic substance content of 99.4% (water content of 0.4%). Yield 89%.

Example No. 5 (scaling).

25 kg (134.4 mol) of hexafluorobenzene (99.7% of the basic substance), a solution of 12.5 kg (312.5 mol) of NaOH in 35 l of water are placed in a 63 L steel reactor for pressure purposes, equipped with a stirrer and 0.75 kg (1.85 mol) of tetrakis (diethylamido) phosphonium bromide. The reaction mass is heated with stirring to 120 ° C for 24 hours, while the pressure drops from 4.8 atm. up to 2.1 atm., and the conversion of hexafluorobenzene reaches 100%. Then the reaction mass is cooled, filtered, the filtrate is acidified with sulfuric acid. The organic layer containing pentafluorophenol and up to 20% water is separated and rectified. Get 22.75 kg of pentafluorophenol with so Kip. 142-143 ° C, mp 35-36 ° C and a basic substance content of 99.4% (water content of 0.4%). Yield 92%.

Claims (4)

1. The method of producing pentafluorophenol by the reaction of hexafluorobenzene with aqueous solutions of hydroxides of alkali and alkaline earth metals, characterized in that the process is carried out in the presence of a phase transfer catalyst at a temperature of 100-140 ° C. 2. The method of producing pentafluorophenol according to claim 1, characterized in that the phase transfer catalyst is used in a concentration of from 0.5 to 10 wt.% Of the amount of the starting hexafluorobenzene, preferably 2-5%. 3. The method of producing pentafluorophenol according to any one of claims 1, 2, characterized in that tetrakis (dialkylamido) phosphonium chlorides or bromides, or N, N ', N ”-hexaalkyl substituted guanidinium, or mixtures thereof are used as phase transfer catalysts. 4. The method of producing pentafluorophenol according to any one of claims 1 to 3, characterized in that 2.05-2.35 equivalents of an alkaline reagent are used with respect to hexafluorobenzene in the form of a 20-30% aqueous solution.