DE1233861B - Process for the preparation of cycloalkylaryl ketones - Google Patents

Description

GERMAN <^ 0τ9 ^ PATENT OFFICE

German class: 12 ο -25

EDITORIAL

Number: 1233 861

File number: S 90341IV b / 12 ο

1 233 861 filing date: April 2, 1964

Opened on: February 9, 1967

The present invention relates to a process for the preparation of cycloalkylaryl ketones from aromatic ones Hydrocarbons and cycloaliphatic carboxylic acids.

It is known that ketones by means of the Friedel-Crafts reaction by conversion of aromatic hydrocarbons with carboxylic acids or their derivatives such as chlorides and anhydrides in the presence of catalysts such as anhydrous aluminum trichloride, which is the most widely used condensing agent represents, can be produced. Although aluminum trichloride is only a catalytic one Has function, it is necessary to achieve good yields of ketones, large amounts of the same use. For example, when a carboxylic acid is used as the acylating agent, 5 to 6 moles per mole of acid are required. In addition, these known methods have the considerable disadvantage that the aluminum chloride used in the reaction cannot be recovered, therefore the process is uneconomical, especially when carried out on an industrial scale will. Another disadvantage of those commonly used in the known condensation processes Condensation agent consists in applying this to the materials used to manufacture the industrial Systems are used, are considerably corrosive.

As a condensing agent in the reaction between aliphatic carboxylic acids and aromatic ones Hydrocarbons for making alkyl aromatic ketones, such as acetophenones, are used of polyphosphoric acid (F. D. P ο ρ ρ, Chem. Reviews, Vol. 58, 1958, p. 384) has already been proposed been. However, the use of such a condensing agent is limited to manufacture alkylaromatic ketones, and in addition, due to secondary reactions that occur, one of which is the intramolecular condensation of the ketones so formed, very low yields achieved.

The present invention now relates to a process for the preparation of cycloalkylaryl ketones from aromatic hydrocarbons and cycloalkanecarboxylic acids, having 4 to 12 carbon atoms in the ring in the presence of an acidic condensing agent, which is characterized in that as the acidic condensing agent, as known from similar reactions, polyphosphoric acid with a Total content of phosphoric anhydride between and 85%> preferably between 80 and 85%, used and at 60 to 150 ⁰ C, preferably 85 to Process for the production of
Cycloalkyl aryl ketones

Applicant:

Societä Edison, Milan (Italy)
Representative:

Dipl.-Ing. Dipl.-Chem. Dr. phil. Dr. techn.
J. Reitstötter and Dr.-Ing. W. Bünte,
Patent Attorneys, Munich 15, Haydnstr. 5

Named as inventor:
Corrado Brichta, Milan;
Giuseppe Ribaldone, Gallarate-Varese;
Adriano Nenz, Milan (Italy)

Claimed priority:

Italy April 6, 1963 (7266)

100 ⁰ C, is worked. The much less economical anhydrides or acyl halides therefore do not need to be used.

When using the cycloalkanecarboxylic acids, no undesirable side reactions are observed either.

The condensing agent used can also be easily recovered and corroded the materials used in the devices do not.

At the temperature used, the polyphosphoric acid is sufficiently liquid to achieve the intended Carry out condensation without interference, a good reaction course with sufficiently high To obtain reaction rates and good yields.

The method according to the invention can be shown schematically as follows:

Ar - H + R - COOH> Ar - CO - R + H ₂ O

where Ar is a residue of an aromatic hydrocarbon and R is a residue of a cycloaliphatic hydrocarbon represents having a ring of 4 to 12 carbon atoms. Examples of aromatic hydrocarbons, which are suitable according to the invention are benzene, toluene, xylene, ethylbenzene, cumene and in general all mono- and polyalkylated derivatives of benzene.

Examples of cycloaliphatic carboxylic acids used in the process of the invention are: Cyclopentanecarboxylic acid, Hexahydrobenzoic acid, Cyclooctanecarboxylic acid, Cyclohen-

709 508/341

decanecarboxylic acid, cyclododecarboxylic acid and when using aromatic hydrocarbons, their alkyl-substituted derivatives, such as 4-methylcyclo- which are monosubstituted by alkyl groups, such as hexanecarboxylic acid. Toluene, ethylbenzene or cumene, or if used

The aromatic hydrocarbons used in the process according to the invention, which are disubstituted by alkyl-polyphosphoric acid as the condensing agent, are disubstituted by 5 groups in the 1- and 3-positions, as in the usual known processes, ie m-xylene, or when using aromatic carbons by prolonged heating Orthophosphoric acid on hydrogens trisubstituted by alkyl groups in 1-, 3- and higher temperatures until the desired Concentric 5-position, such as 1,3,5-trimethyltration on phosphoric anhydride, or benzene, the carbonyl group occupies the 4- Position.
by dissolving the calculated amount of phosphorus io If, by alkyl groups at the 1- and anhydride in orthophosphoric acid. The 4-position disubstituted hydrocarbons, the position of polyphosphoric acid is very variable, the carbonyl group with respect to one of the alkyl and contains a mixture of orthophosphoric acid, substitutes in the ortho position, while in pyrophosphoric acid and linear polyphosphoric acid aromatic hydrocarbons with trisubstitute - (FD P ο ρ ρ, WE McE ν e η, "Chemical Re- 15 ierter Alkylgrappe in 1-, 3- and 4-position die Carviews", Vol. 58, 1958, p. 324). bonyl group occupies the 6-position.

Although the molar ratio between the cyclo- The alkanecarboxylic acid according to the invention and the aromatic carbon-containing ketones are valuable intermediate hydrogen can therefore fluctuate within wide limits, products for the manufacture of pharmaceutical products will give good results if they are used with molar 20s and monomers from which Plastic fiber ratios between 0.1 and 10 and preferably and molded bodies can be produced,
between 0.3 and 0.4 is worked. The following examples illustrate the present

The amount of according to the present invention. . • I ₁

polyphosphoric acid used, expressed in moles Example
In a phosphoric acid per mole Cycloalkancarbon- 25 with a stirrer, a thermometer, varies from 1 mole up to 9 to 10 moles and a reflux condenser and 250 cc Kolliegt preferably at about 5 mol. 13.8 g were ben hexahydrobenzoic acid, 30 ecm

It was found that the reaction time ent- toluene and 70 g of polyphosphoric acid given the reactivity of the cycloalkane total content of 85% phosphoric anhydride, carboxylic acid and the aromatic hydrocarbon 30. The mixture was then varied with vigorous stirring and was between 30 minutes and 6 hours. Heated to 100 ° C for 6 hours. The reaction mass

It has been found that it is advantageous for the ab- was cooled to room temperature and then with treated separation of the ketone from the reaction mass by 100 ecm of ice water.

Extraction with the same aromatic charcoal The mixture was repeated with ether hydrogen, which was extracted as starting 35 in the reaction, and the collected ether extracts were used, using the then three times with 10 ecm of a 10% aqueous heat of reaction or washed by diluting the re sodium hydroxide solution. In the alkaline action mass with water and subsequent ex-extract, 0.21 g was not reclassified with solvents by titration. Equated hexahydrobenzoic acid found,
The ether solution was then dried over anhydrous organic extract in addition to the sodium sulphate during the reaction and the ether in a ketone produced also the cycloalkanecarboxylic acid, water bath evaporated. After removing the last one that was not implemented; This can easily be done from the traces of the solvent by evaporation in the organic extract according to known methods, vacuum, which mainly consisted of excess toluene such as treating the extract with aqueous, 45 , 19.8 g of cyclohexyl-p-tolyl ketone (entalkaline solutions and subsequent acidification , speaking of a yield of 92.5 ° / ₀ > calculated on to be removed. the converted hexahydrobenzoic acid) as a light yellow,

Another suitable method for separating crystalline residue obtained
the unreacted cycloalkanecarboxylic acid was then subjected to vacuum distillation in the organic extract of the fractionated 50 17.5 g of pure cyclohexyl-p-tolyl ketone with a boiling distillation in vacuo, so that the point from 97 to 100 ° C / 0.15 mm Hg and a solvent containing the cycloalkanecarboxylic acid and the melting point of 65 to 66 ° C.
Ketone can be obtained separately. The oxime was made from this product,

If you work as described above, it showed a melting point of 168 ° C, which is possible because the poly-55 used in the reaction corresponds well to the values in the phosphoric acid from the inorganic residue niche literature,
regain and use again after. .

the total content of P ₂ O ₅ using known methods

drive brought back to the desired value In the apparatus described in Example 1, the polyphosphoric acid in the heat 60 , 13.8 g of hexahydrobenzoic acid, 60 ecm of toluene were concentrated or the calculated amount of phosphoric and 70 g of polyphosphoric acid with a total content of phosphoric anhydride can be added. This introduced from 85% phosphoric anhydride. This enables a continuous implementation of the entire mixture was then 6 hours at 85 ° C process on an industrial scale. held while stirring vigorously at the same time. so

The yields of 65 prepared according to the invention, the reaction mass to room temperature cycloalkylaryl ketones fluctuate between 90 and cooled, treated with 100 ecm of ice water and 100% of the theoretical yield, based on the finally repeatedly extracted with ether. The converted cycloalkanecarboxylic acid. collected ether extracts were used three times

10 ecm of an aqueous, 10% sodium hydroxide solution. Were obtained from the alkaline extract by acidification with dilute hydrochloric acid, extraction with ether and evaporation of the solvent 2.73 g of unreacted hexahydro-s benzoic acid were obtained.

The ether extracts dried over anhydrous sodium sulfate were concentrated on a water bath and after removing the last traces of the solvent by evaporation in vacuo, 16.6 g of cyclohexyl-p-tolyl ketone obtained as a light yellow, crystalline residue. The yield based on the converted Hexahydrobenzoic acid, was 95.6%. Distillation in vacuo gave the crude product

15.4 g of pure cyclohexyl-p-tolyl ketone with a boiling point of 113 to 115 ° C / 2mmHg and a Melting point of 66 ° C.

Example 3

In an apparatus described in the preceding examples, a mixture of 13.8 g of hexahydrobenzoic acid, 4.5 g of polyphosphoric acid (with a total content of 76% P2O5) ^U1 * d 60 ecm of toluene was heated to 115 ° C. for 6 hours.

The still hot reaction mass was poured into a liquid extractor and extracted with toluene. The toluene solution thus obtained was three times with 20 ecm of a 10% aqueous sodium hydroxide solution washed. In the alkaline extracts, 3.4 g were unreacted by titration Hexahydrobenzoic acid found.

The collected toluene extracts were dried over anhydrous sodium sulfate and then concentrated to dryness by evaporation of the solvent in vacuo. The residue was 13.7 g obtained light brown cyclohexyl-p-tolyl ketone.

The yield of cyclohexyl-p-tolyl ketone, based on the converted hexahydrobenzoic acid, was

83.5 «/ ο.

Example 4

As in the previous examples, a mixture of 13.8 g of hexahydrobenzoic acid, 30 ecm of benzene and 70 g of polyphosphoric acid (total P ₂ O ₅ content = 80%) was reacted for 6 hours at 80 to 85 ° C. In the alkaline extracts 10.2 g unreacted hexahydrobenzoic found, while in the ether extracts 5 g of a residue was obtained, the g after distillation in vacuo 3.9 cyclohexyl phenyl ketone having a boiling point 165-166 ° C / 20mmHg and a melting point 52-53 ⁰ C. yielded.

Example 5

Under the conditions of the preceding examples, 13.8 g of hexahydrobenzoic acid, 35 cc of p-xylene and 70 g of polyphosphoric acid (with a total content of 85% P ₂ O ₅₎ are reacted at IOO 6 hours ⁰ C.

4.7 g of unreacted hexahydrobenzoic acid were found in the alkaline extracts. By Concentration of the ether extracts gave 12.2 g of cyclohexyl (2,5-dimethylphenyl) ketone as a solid residue obtained with the following elemental analysis:

65

Found C 84.9%, H 9.7%;

calculated
MrC ₁₅ H ₂₀ O ... C 83.3%, H 9.3%.

The yield of ketone, based on the converted hexahydrobenzoic acid, was 79.4%.

7.1 g of this product gave 5.3 g of pure cyclohexyl (2,5-dimethylphenyl) ketone after vacuum distillation with a boiling point of 113 to 115 ° C / 0.2 mm Hg and a melting point of 43 to 44 ° C

The product also showed the following elemental analysis:

Found ... C 84.0%;

H 9.6%.

The infrared absorption spectrum showed the following characteristic maxima (expressed in microns ± 0.02): 5.93, 6.70, 8.58, 11.15, 11.33, 12.28, 12.74.

The measurements were made in KBr tablets. From the obtained as described above Cyclohexyl (2,5-dimethylphenyl) ketone was used to prepare the corresponding oxime. This, from a benzene-petroleum ether mixture crystallized, melted at 152 to 153 ° C and resulted in the following elemental analysis:

Found C 78.5%, H 9.6%, N 5.8%;

calculated

for C ₁₅ H ₂₁ NO, C 77.8%, H 9.2%, N 6.0%.

Example 6

In the same apparatus and as described in Example 1 according to the same procedure, 13.8 g hexahydrobenzoic acid, 35 cc of ethylbenzene and 70 g polyphosphoric acid (with a total content of 85% phosphoric anhydride) with vigorous stirring for 6 hours at IOO were reacted ^0C.

3.8 g of unreacted hexahydrobenzoic acid were found in the alkaline extracts.

By concentrating the ether extracts, 14.1 g of cyclohexyl (4-ethylphenyl) ketone were obtained as a solid residue obtained with the following elemental analysis:

Found C 84.0%, H 9.8%;

calculated

for C ₁₅ H ₂₀ O .. C 83.3%, H 9.3%.

The yield, based on the converted hexahydrobenzoic acid, was 83.5% x 8.3 g of the product after distillation resulted in 7.2 g of pure cyclohexyl (4-ethylphenyl) ketone with a boiling point of 123 up to 126 ° C / 0.4mmHg and a melting point of 50 to 51 ° C as well as the following elemental analysis:

Found ... C 84.2%;

H 9.5%.

The infrared absorption spectrum showed the following characteristic maxima (expressed in microns ± 0.02): 6.00, 6.23, 6.37, 7.98, 8.23, 8.42, 8.52, 10.25, 11.65, 11.91.

The measurement was carried out in KBr tablets. The cyclohexyl (4-ethylphenyl) ketone became the oxime produced, which melted after crystallization from a benzene-petroleum ether mixture at 153 to 144 ° C and the following elemental analysis resulted:

Found C 77.9%, H 9.4%, N 6.2%;

I? qx c cli n et

for C ₁₅ H ₂₁ NO C 77.8%, H 9.2%, N 6.0%

Example 7

In the same apparatus and in the same manner as described in Example 1, 13.8 g of hexahydro-

Claims (2)

benzoic acid, 35 ecm of m-xylene and 70 g of polyphosphoric acid (with a total content of 85% phosphoric anhydride) heated to 100 ° C. for 3 hours. 0.85 g of hexahydrobenzoic acid was removed from the alkaline extracts. 18.1 g of a liquid residue were obtained from the ether extracts by evaporation of the solvent. Pure cyclohexyl (2,4-dimethylphenyl) ketone with a boiling point of 105 to 107 ° C / 0.15 mmHg and a refractive index n2g = 1.5370 with the following elemental analysis was obtained by vacuum distillation: Found C 84.1%, H 9 , 4%; for C15H20O ... C 83.3%, H 9.3%. The infrared absorption spectrum showed the following characteristic maxima (expressed in microns ± 0.02): 5.95, 6.20, 6.39, 8.02, 8.29, 10.25, 12.18, 12.46, 12, 82. Example 8 In the same apparatus and in the same manner as described in Example 1, 13.8 g of hexahydrobenzoic acid, 40 ecm of cumene and 70 g of polyphosphoric acid (with a total content of 85% phosphoric anhydride) were heated to 100 ° C. for 6 hours. 2.5 g of hexahydrobenzoic acid were removed from the alkaline extracts. 11.9 g of a liquid residue were obtained from the ether extracts by evaporation of the solvent, which after distillation in vacuo was pure cyclohexyl (4-isopropylphenyl) ketone with a boiling point of 120 to 125 ° C / 0.3 mm Hg and a refractive index ns§ = 1.5334 and the following elemental analysis gave: The infrared absorption spectrum showed the following characteristic maxima (expressed in microns ± 0.02): 5.95, 6.22, 6.36, 8.47, 8.95; and the following maxima with respect to the cycloalkyl group: 6.8, 6.9, 7.1, 7.25, 7.32. The oxime was prepared from the cyclooctyl-p-tolyl ketone, which, crystallized from a benzene-petroleum ether mixture, melted at 148 to 150 ° C. and gave the following elemental analysis: Found C 79.0%, H 9.3%, N 6 ,1%; for C16H23NO: C 78.3%, H 9.45%, N 5.7%. Example 10 In the same apparatus and in the same manner as described in the previous examples, a mixture of 13.6 g of cyclododecanecarboxylic acid, 18 ecm of toluene and 40 g of polyphosphoric acid (with a total content of 85% phosphoric anhydride) was heated to 100 ° C. for 4 hours. 6.7 g of cyclododecanecarboxylic acid were recovered from the alkaline extracts. A crystalline product which was mixed with traces of an oily product and weighed 7.6 g was obtained from the ether extracts by evaporation of the solvent ° C / 0.3 mm Hg and after crystallization from petroleum ether with a melting point of 63 to 65 0C resulted. The resulting product showed the following elemental analysis: found C 83.9%, H 10.2%; calculated for C20H30O ... C 83.8%, H 10.5%. 40 45 50 Found C 83.2%, H 9.7%; for C16H22O ... C 83.4%, H 9.6%. The oxime was prepared from this product, which crystallized from a benzene-petroleum ether mixture, had a melting point of 163 to 164 ° C and gave the following elemental analysis: Found C 78.8%, H 9.6%, N 5.5% ; Calculated MrC16H23NO C 78.3%, H 9.45%, N 5.7%. EXAMPLE 9 In the same apparatus and in the same manner as described in Example 1, 20 g of cycloctanecarboxylic acid, 36 ecm of toluene and 80 g of polyphosphoric acid (with a total content of 85% P2O5) were heated to 100 ° C. for 3½ hours. 1.4 g of cyclooctanecarboxylic acid were obtained from the alkaline extracts. 31 g of an oily residue were obtained from the ether extracts by evaporation of the solvent, from which 26 g of cyclooctyl-p-tolyl ketone with a boiling point of 140 to 145 ° C / 0.5 mmHg, a refractive index nf - 1.5481 and the following elemental analysis were obtained by vacuum distillation obtained: Found C 83.4%, H 9.1%; for C16H22O ... C 83.4%, H 9.6%. The infrared absorption spectrum had the following characteristic maxima (expressed in microns ± 0.02): 5.96, 6.23, 6.37, 8.05, 8.34, 8.46, 8.56, 12.92, 13 , 75, 13.92. The measurement was carried out in KBr tablets. Patent claims: 1. A process for the preparation of cycloalkylaryl ketones from aromatic hydrocarbons and cycloalkanecarboxylic acids with 4 to 12 carbon atoms in the ring in the presence of an acidic condensation agent, characterized in that the acidic condensation agent, as known from similar reactions, is polyphosphoric acid with a total content of phosphoric anhydride between 73 and 85% > preferably between 80 and 85%, and used at 60 to 150 ° C, preferably 85 to IOO ⁰ C, is carried out. 2. The method according to claim 1, characterized in that with a molar ratio of P ₂ O ₅ / cycloalkanecarboxylic acid between 1 and 10, preferably about 5, and a molar ratio of cycloalkanecarboxylic acid to aromatic hydrocarbon of 0.1 to 10, preferably 0.3 to 0.4, is worked. Considered publications:
Belgian patent specification No. 633 124;
Chem. Reviews, Vol. 58, 1958, pp. 321-401. 709 508 / 3M 1.67 © BundesdruckereiBerlin