DE1127340B - Process for the preparation of fluorine-containing aromatic ketones - Google Patents

Description

Process for the preparation of fluorine-containing aromatic ketones The process relates to the production of ketones of the general formula Ar-CO- (CF2) nR where Ar is an aromatic radical as defined below, R is a hydrogen or halogen atom and n mean an odd integer.

For the production of fatty aromatic fluorine-containing ketones are various processes with a limited range of applications are known. So were Friedel-Crafts synthesis by means of aluminum chloride from benzene and fluorinated acetyl chlorides mono-, di- and Obtained trifluoroacetophenone. It is also known that difluoroacetophenone also from acetophenone by direct fluorination with a mixture of fluorine and hydrogen fluoride or from dibromoacetophenone by halogen exchange using hydrogen fluoride and silver fluoride can be produced. The Friedel-Crafts synthesis with metal chloride catalysts but is because of the easy replacement of fluorine atoms by chlorine atoms and in particular because of the characteristic proportions at the aromatic nucleus, which are expressed in the well-known substitution rules, only applicable to a limited extent, while the side chain fluorination of fatty aromatic ketones is cumbersome and proceeds with low yield. So far only have been able to achieve satisfactory yields Ketones by reacting aromatic Grignard or lithium compounds with perfluorocarboxylic acids getting produced. This method is limited to perfluoroalkyl-aryl-ketones and requires the not always easy production and use of organometallic Output connections.

The process according to the invention enables, in a simple manner, the production of fluorine-containing fatty aromatic ketones with a keto group in the nucleus, in which the side chain attached to the keto group can be of different lengths and in which the aromatic nucleus can be further substituted. Such ketones are obtained by the process of the invention by the action of strong mineral acids on aromatic compounds of the general formula in which R is a hydrogen or halogen atom, R 'is a hydrogen or halogen atom, an alkyl, cycloalkyl, aryl or alkoxyl radical, the nitrile group, the nitro group, the free, amidated, esterified or halogenated carboxyl group, the free, amidated, esterified or halogenated sulfonic acid group which represents free or protected amino group and two adjacent substituents R 'can also be designed in such a way that they are linked to one another - as in the case of naphthalene or tetrahydronaphthalene - to form a new ring, and n is an uneven number means. It is irrelevant here if sensitive substituents R 'are changed under the reaction conditions, as is possible, for example, when the acid amide group changes to the nitrile group with elimination of water, provided that this change can be reversed after the reaction. Of course, sensitive substituents can also be protected from the action of acids in a known manner.

The ketones obtained according to the invention correspond to the general formula: wherein R, R 'and n have the meaning given above. Most of these compounds are new substances.

The starting materials for the process are due to the addition of tetrafluoroethylene to aromatic compounds according to the methods of German patents 1058 980 and 1,064,045 easily and in many cases with very good yields. You are stable Compounds that give the normal reactions of aromatic bodies and in particular characterized by the extremely strong bond of their fluorine atoms in the side chains.-It However, it was found that when heated with strong acids, an exchange of two neighboring nuclei Fluorine atoms versus oxygen with formation of a ketone takes place, which in very good Yields is obtained.

Suitable acids are concentrated mineral acids such as phosphoric acids, Nitric acid, perchloric acid, but especially sulfuric acid and oleum.

Although the exchange of fluorine atoms for an oxygen atom at the nucleus adjacent Carbon atom has the character of a hydrolysis, the reaction proceeds with it decreasing water content of the reaction medium better. The course of the reaction depends on the type and position of the substituents in the nucleus and on the length of the fluorine-containing ones Side chain from, so that with substances with certain core substituents and longer more vigorous conditions apply to fluorine-containing side chains.

The reaction is exothermic and is activated by heating the fluorine-containing aromatic compounds with the mineral acid to temperatures of 100 to 250 ° C initiated. The beginning of the reaction is due to a rise in temperature, gentle foaming or gas evolution can be easily recognized. It is for a smooth reaction process it is often expedient to submit one component and the other in accordance with the course of the reaction to add. When the addition of the second component is complete, it reacts quickly Mixtures complete the reaction within a few minutes, while being less violent reacting mixtures advantageous for some time, for example up to 60 minutes, holds at the reaction temperature. In cases where the reaction is sluggish, you can also mix both components cold, heat them together and for so long hold at the reaction temperature until the reaction has ended. To the attack of the The reaction mixture can be used to reduce the amount of hydrogen fluoride formed on the walls of the vessel add some precipitated silica.

When using excess pure sulfuric acid, however, is the Development of gaseous hydrogen fluoride very little, which is due to its chemical Suggesting binding in a secondary reaction.

The mineral acid is used in at least an equimolar amount; An excess of 0.5 to 5 mol is advantageous.

The reaction mixture can be worked up in various ways take place. In the case of high-boiling or crystallizing reaction products, the After cooling, the mixture can be poured onto ice or diluted with water, whereupon the oily or crystalline precipitating ketone is separated off. Will be volatile ketones isolated by distillation. Isolation by steam distillation is particularly easy, where steam is passed into the reaction mixture after the reaction has ended and separates the ketone which precipitates out of the distillate as heavy oil.

While the sales, for example, when using sulfuric acid and oleum are very high and When approaching 100 per cent, they are used by others inorganic acids such as phosphoric acid or concentrated nitric acid lower. However, the use of these acids can be advantageous in such cases which the use of sulfuric acid or oleum because of too rapid progress Prohibits sulfonation.

The ketones produced by this process are chemically extraordinary stable substances, hardly even from strong acids and acidic oxidizing agents to be attacked. They show the usual reactions of ketones; their dinitrophenylhydrazones are mostly dimorphic. The ketones serve as intermediates for the manufacture of Dyes and for the production of other fluorine-containing compounds. They are as a result their stability suitable as heat transfer fluids. The procedure will illustrated by the following examples: Example 1 In a 500 ml round bottom flask 89 g of tetrafluoroethylbenzene (0.5 mol) are heated to 125 ° C. with stirring. Within 125 ml of pure sulfuric acid (monohydrate) are added dropwise from 30 minutes, whereupon the mixture is stirred at 125 ° C. for a further 30 minutes. By introducing steam a distillate is obtained from which the ec, o; -difluoroacetophenone is deposited. The pure distillation gives the pure ketone with a boiling point of 10 = 66 ° C in a 92% yield ; n'D '= 1, 4978. The two dinitrophenylhydrazones are yellow (mp = 126 ° C) or deep orange (F. = 226 ° C) colored.

Example 2 The same amount of tetrafluoroethylbenzene as above was used with a mixture of 162 g 86.5 "/ piger phosphoric acid and 60 g phosphorus pentoxide treated at 125 to 135 ° C as above. Work-up yielded 73 g unchanged Starting material and 10 g DiSluoroacetophenon. When using 200 g of 70% nitric acid delivered the same amount of tetrafluoroethylbenzene in addition to 68 g of unchanged starting material a mixture of 16 g of m-nitrotetrafluoroethylbenzene, 2 g of difluoroacetophenone and 5 g higher-ruined compounds as residues. These two experiments show that Sulfuric acid is superior to the other mineral acids with basically similar behavior is.

Example 3 106 g of o-chloro-tetrafluoroethylbenzene (n2D = 1.4564) were with 100 ml of concentrated sulfuric acid and 20 g of silica at 125 to 130 ° C, as described in Example 1, implemented and worked up. That in one yield o-chlorine, a-difluoroacetophenone obtained from 79% of theory is colorless Liquid with a boiling point of is = 110 ° C and n'DI = 1.5131.

CgHsOCIF, (190,6).

Calculated C 50.4 "/., H 2> 7 ° / o Cl 18.6 ° / o, F 19n6 ° / o; found C 50, 1 ° / o, H 2, 7 "/, Cl 18, 5 duos F 19, 2" / ..

The isomeric p-chloro-a obtained from p-chloro-tetrafluoroethylbenzene, α-difluoroacetophenone shows as constants: b.p. lo = 96 ° C, nD20 = 1.5182.

Example 4 112 g of m-nitro-tetrafluoroethylbenzene (0.5 mol) were with 20 g of silica and 100 ml of concentrated Sulfuric acid 45 Heated to 180 to 190 ° C for minutes.

After cooling, the mixture was poured onto 500 g of ice. The unusual Crystals were combined with the ether extract of the aqueous layer and recrystallized from carbon tetrachloride the pure m-nitro-a, a-difluoroacetophenone in large light yellow Crystals with a melting point of 64.5 ° C. were obtained in a yield of over 80% of theory.

C8Hb03NF2 (201, 1).

Calculated C47.9%, H 2.5%, N 6.7%, F 18.9%; found C 48.1%, H 2.8%, N 6.9%, F 18.7%.

The identity was established by nitration of difluoroacetophenone and comparison of the two connections ensured.

Example 5 52 g of m-tetrafluoroethylbenzenesulfofluoride (ho = 1.4440) were reacted with 10 g of SiO2 and 100 ml of concentrated sulfuric acid at 150 ° C. After cooling, the mixture was stirred with ice, extracted with ether and the ether solution with sodium bicarbonate and washed water. The oil remaining after evaporation of the ether was at 95 Distilled to 98 ° C at a pressure of 0.5 Torr, showed a refraction of n'Do = 1.4949 and solidified to form large colorless crystals with a temperature of 27 ° C. After the analysis it is the compound obtained in a yield of 50% of theory around the m-sulfofluoride of the difluoroacetophenone.

C8H5O3SF3 (238,2).

Calculated C 40.3%, H 2.2%, S 13.5%, F 23.9%; found C 39.7%, H 2.2%, S 13.4%, F 24.0%.

Example 6 213 g o αß, ß-tetrafluoro-ß-chloroethylbenzene (bp 75 = 84 ° C, nD20 = 1, 4330), prepared in the usual way for side chain chlorinations by chlorination of tetrafluoroethylbenzene in carbon tetrachloride under ultraviolet radiation at 78 ° C, were heated with 20 g of SiO2 with stirring to 125 ° C, whereupon within 150 g of pure sulfuric acid were added dropwise for 1 hour with the temperature increasing to 137 ° C became.

After an additional reaction time of 15 minutes at 140 ° C was Introduced steam into the mixture and fractionated the crude ketone which had passed over Purified distillation. The α, α-difluoro-α-chloroacetophenone from Bp 13 = 72 ° C and n'D '= 1.4960 was obtained in 92% pure yield.

C, H, OCIF, (190, 6).

Calculated ... C 50.4%, H 2.6%, F 19.9%; found ... C 50.6%, JH 2.9%, F 20.3%.

Example 7 A Tekailuoroethyltoluene of the refraction nD20 = 1, 4371, the consisted of the o- and p-isomers, was according to the information in Example 1 at 135.degree unset in a yield of 93% of theory for the corresponding ketone mixture. This showed the constants bp 22 = 96 to 98 ° C., nD20 = 1,4981.

C9H8OF2 (170,2).

Calculated ... C 63.5%, H 4.7%, F 22.3%; found ... C 63.2%, H 4.7%, F 23.1%.

Example 8 α, α, β, β, γ, γ-hexafluorobutyrophenone In the mixture of 55.6 g of octafluorobutylbenzene (b.p. 13 = 62 ° C, nD20 = 1.3926) and 10 g of silica are at 220 ° C 40 g of concentrated sulfuric acid within Entered for 30 minutes with stirring. Hold at the same temperature for another 30 minutes, pour on ice and extract the mixture with chloroform.

The combined chloroform phases are washed with water and washed over Dried sodium sulfate. After evaporation of the solvent and fractional vacuum distillation of the residue is obtained in addition to 8.9 g (15.8%) starting compound 24.2 g (56, 2% of conversion) pure hexafluorobutyrophenone, boiling point 31.5 = 103 ° C, nD20 = 1, 4335.

CloH6OF6 (256,2).

Calculated C 46.9%, H 2.4%, F 44.5%, Cl 0%; found C 46.7%, H 2.5%, F 44.3 "/., Cl 0.75 / 0.

2,4-Dinitrophenylhydrazone (from methanol): M.p. = 91 to 92 ° C.

Example 9 m-nitro-α, α, β, β, γ, γ-hexafluorobutyrophenone The mixture of 50 g of m-nitrooctafluorobutylbenzene (b.p. l2 = 131 ° C, nD20 = 1, 4326) and 3 g of glass wool is mixed with 50 g of 100% strength at 200 ° C. within 30 minutes while stirring Sulfuric acid ("monohydrate") is added and a further 30 minutes at the same temperature held. You work up as in the previous example. When fractionating in a vacuum 34.7 g (corresponding to 74.6% of theory) of m-nitrohexafluorobutyrophenone are obtained. The product purified for analysis shows the following values: b.p. 3 = 110 ° C, n2D0 = 1, 4678.

C10H5O3NF6 (301, 1).

Calculated C 39.9 ° / 0, H 1.7%, N 4.7%, F 37.8%; found C 39.9 ° / 0, H 1.9 ° / o, N 4.9 ° / 0, F 38.6 ° / o.

Example 10 o, α, ß, ß, γ, y, #, #, #, # - Decafluorcaprophenone 100 g dodecafluorohexylbenzene and 130 g 100% sulfuric acid (»monohydrate (x) are heated with stirring to 220 ° C and stirred for 1 hour at this temperature. After cooling, ice is added and the mixture is extracted with methylene chloride. The organic phases are combined, washed with water, over sodium sulfate dried and evaporated. The residue is fractionated in vacuo. You get 37g (corresponding to 39.3% of theory) of pure decafluorocaprophenone, b.p. 2o = 117 ° C, nD20 = 1,4100.

Ci2H6OFio (356,2).

Calculated ... C 40.5%, H 1.7%, F 53.4%; found .. C 40.4 ° / 0, H 2.0 ° / o, F 52.1 ° / o.

Example 11 c-H-Tetradecafluorocaprylophenone. 19.1 g hexadecafluorooctylbenzene, which contained a small amount of the isomeric bis-octafluorobutylbenzene, and 16 g of 20% oleum are heated to 160 ° C. in the course of 2 hours and then for 1 hour held at this temperature. Ice is added and the mixture is shaken with methylene chloride.

The combined extracts are washed with water over sodium sulfate dried and evaporated. You win from the residue The pure tetradecafluorocaprylophenone is vacuum distilled over a spinning band column in a yield of 7.2 g (corresponding to 39.5% of theory); Kp. Lo = 127 to 127.5 ° C, nD20 = 1.3949.

Cl4H6OFl4 (456,2).

Calculated ... C 36.9%, H 1.3%, F 58.3%; found ... C 36.6%, H 1, 6%, F 56.6%.

The ketone contained a small amount of that obtained from the isomeric bis-octafluorobutylbenzene 1, 3-bis-hexafluorobutyrylbenzene formed, which is oxidized to form isophthalic acid has been proven.

Example 12 6-chloro-3-nitro-os, Lx-difluoroacetophenone To 100 g of 6-chloro-3 Nitro-tetrailuoroethylbenzene (temperature = 46 to 47 ° C.) is added at 180 ° C. with stirring 75 g of 10% oleum and heated to 180 ° C for a further 10 minutes. One relocates cooling with ice and shaking the mixture with methylene chloride. The extract is washed with water and soda solution, dried over sodium sulfate, the solvent evaporated and the residue fractionated in vacuo. After 13.4 g (13.4%) starting material 54.4 g (66% of conversion) 6-chloro-3-nitrodifluoroacetophenone go over. That through repeated distillation of purified ketone boils at a pressure of 12 torr 152 ° C, ho = 1.5502.

CSH403NC1F2 (235,6).

Calculated: C 40.8%, H 1.7%, N 6.0%, Cl 15.0%, F 16.1%; found : C 40.8 ° / o, H 2, 0 ° / o, N 6,%, Cl 14.7%, F 16.4 ° / 0.

2,4-Dinitrophenylhydrazone: yellow, silky needles with a temperature of 182 ° C (from methanol).

Methyl half-ketal: colorless crystals of F.

= 106 ° C (from methanol).

C9H8O4NF2Cl (267,6).

Calculated: C 40.4 ° / 0, H 3, 0 ° / o, N 5, 2%, F 14, 2%, Cl 13, 3% ; found: C 40.0%, H 3, 0%, N 5, 1%, F 14.7%, Cl 13.5%.

The soda solution used for washing above can be acidified a small amount (0.3 g, corresponding to 0.5% of theory) of 6-chloro-3-nitrobenzoic acid from the melting point of 164 ° C that by mixing the melting point with an authentic Preparation is identified.

Example 13 4-chloro-3-nitro-difluoroacetophenone To 20 g of 4-chloro-3-nitro-tetrafluoroethylbenzene (F. = 28.2 ° C.), 40 g of 10% strength is added dropwise at 180 ° C. with stirring over the course of 5 minutes Oleum, heated to 200 ° C and left the reaction mixture for 5 minutes at this temperature. After cooling, ice is added and the mixture is extracted thoroughly with methylene chloride. The combined methylene chloride layers are washed with water and then with soda solution washed and dried over sodium sulfate. The one when the solvent evaporates any oily residue that remains is fractionated in vacuo. Man receives 8 g (corresponding to 43.8% of theory) 4-chloro-3-nitro-difluoroacetophenone, b.p. 5 = 131 ° C, nD20 = 1.5504 as a pale yellow oil that crystallizes immediately when rubbed. After this Recrystallization from n-pentane melts the compound at 34 to 35 ° C.

C8H403NC1F2 (235, 60).

Calculated: C 40.8%, H 1, .7%, N 6, 0%, Cl 15, 0%, F 16, 1%; found: -C 41.2 ° / o, H 1.9 "/., N 6.0%, Cl 14.9%, F 15.9% -2, 4-dinitrophenylhydrazone : orange-colored crystals with a temperature of 194 ° C (from ethyl acetate).

The soda solution used for washing above is obtained by acidification 2.33 g (corresponding to 19.4% of theory) of 4-chloro-3-nitro-benzoic acid, melting point = 181 to 182 ° C, identified by the mixed melting point with an authentic preparation will.

Claims (1)

PATENT CLAIM: Process for the production of fluorine-containing aromatic ketones of the general formula in which R is a hydrogen or halogen atom, n is an odd integer and R 'is a hydrogen or halogen atom, an alkyl, cycloalkyl, aryl or alkoxy group, the nitrile group, the nitro group, the free, amidated, esterified or halogenated carboxyl group , the free, amidated, esterified or halogenated sulfonic acid group, the free or protected amino group and two adjacent substituents R 'can be linked to form a new ring, characterized in that one fluorine-containing aromatic compounds of the general formula in which R, R 'and n have the above meanings, treated with mineral acids at elevated temperature and the fluorine-containing aromatic ketones formed in this way isolated by processes known per se. Papers considered: Journal of the American Chemical Society ", Vol. 77 (1955), pp. 3656 to 3658, and Vol. 78 (1, 956), pp. 2268 to 2270 ; "Journal of Organic Chemistry", Vol. 22 (1957), pp. 993 to 994.