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The subject of the invention is a process for the preparation of new arylpropane derivatives of general formula Atr-CH (CH₈)₂wherein Ar is 4'-fluorodiphenylyl, 3-methoxy-4-phenoxyphenyl, 4- (1-cyclooctenyl) -phenyl, 4-cyclooctenyl-5-phenyl or 4- {2-norboimyl) -phenyl. These compounds have valuable healing properties.

By the method of the invention and the compounds of the general formula Ar-CH (CH₈)₂wherein At is as defined above, is prepared by catalytic hydrogenation of compounds of general formula Ar-C (CH₃)₂-OH or Ar-C (CH₈) = CH₂in which the formulas of Ar is as defined above. The first of these hydrogenation processes is preferably carried out in the presence of a palladium catalyst and the second in the presence of platinum oxide as the catalyst. The product obtained is isolated and purified by known methods, e.g. by extracting the filtrate after separating off the catalyst and evaporating the solvent. twenty

The course of the reactions carried out by the process according to the invention is illustrated in Schemes 1 and 2, while these schemes also show the methods of producing the starting products used according to the invention. In the formulas occurring in these schemes, Ar is as defined above, Et is an ethyl radical, R^{1 * * *} is a lower alkyl radical and Ac is an organic acid radical. Some examples of the preparation of these starting products 30 are given below

A. Preparation of 2- (4-diphenylyl) -propanol-2. To a solution of 98 g of 4-acetyldiphenyl in 500 ml of ether and 500 ml of benzene, a 2.25 molar solution of methylmagnesium chloride diluted 1: 1 with ether is added dropwise while stirring. The dropwise addition was carried out so as to maintain the mixture at a gentle boil, after which the mixture was continued to boil gently under reflux for 12 hours.

The mixture is then cooled to room temperature and excess Grignard reagent is decomposed by adding 178 ml of saturated ammonium chloride solution. The organic layer is separated, poured into ice-water, the organic solution is separated again, washed with a dilute bicarbonate solution (sodium carbonate and water, dried over sodium sulfate and the solvents are evaporated in vacuo). The white solid residue is recrystallized from hexane to give 85 g of 2- (4-diphenylyl) -prcpanol-2, mp 88.5-90.5 ° C.

Product analysis.

Ohl · end for formula C.₁₅H._lflO: 84.87% C, 7.60% H, Found: 85.01% C, 7.54% H.

In an analogous manner, from 3-methoxy-4-femokisyacetophenone is prepared from 2- (3-methoxy-4-phenoxyphenyl) -propanol, boiling point 170-1.177 ° C / 0.07 mm Hg⁵ = _ 1,57132.

Product analysis.

Calculated for the formula C10H1₈ABOUT₈: 74.89% C, 7.02% H,

Found: 74.58 · / · C, 7.29 · / · Η.

2- (4'-Fluorodiphenylyl)-2-propanol having a melting point of 110-111 ° C is also obtained in an analogous manner from 4'-fluoro-4-acetyldiphenyl.

Product analysis.

Calculated for the formula Ci₅H.₁₅FO: 78.24 · / · C, 6.57 · / · H, Found: 77.95 · / · C, 6.79 · / H.

B. Preparation of 4-phenyl-α-methylstyrene. A suspension of 42.4 g of 2X4 Tftmylyl) H 2 -ropanol in 100 ml of 4 N sulfuric acid and 50 ml of ethanol is kept under stirring and refluxing for 1.5 hours, then 50 ml of ethanol are added and still boiling for 2.5 hours. The mixture is then cooled to room temperature, poured into ice water and extracted with ether, benzene and chloroform. The extracts are combined with aa, rinsed with a sodium bicarbonate solution and; with water, then dried and evaporated under the pressure of mKKg. The residue was recrystallized from hexane to give

23.4 g of 4ff (siyk) -alpha.-methylsty] eaiu, mp 116-118 ° C.

Product analysis.

Calculated for the formula Ci_S.H._at: 92.74 · / · C, 7.26 · / · H, Found: 92.45 · / · C, 6.98 / · H.

In a similar manner, from - 2- <3-Hmetosy ---- pheicoxyphenyl) -propanol-2, 3-methdxy-4-phenoxy-α-methylstyrene is obtained with a boiling point of 157—160 ° C / 0.07 mm Hg, n £ = 1.5914.

Product analysis.

Calculated for the formula CieHfO,: 79.97 · / · C, 6.71 · / · H, Found: 79.75 · / · C, 6.76 · / · H.

Also in an analogous manner from - 2- (4 '-luorodiphenylyl)-2 -propanol - 4- (4'-fluorophenyl) -αH-methyl styrene, mp 127-128 ° C, is obtained.

Product analysis.

Calculated for formula C.₁₅H._ATF: 84.87 · / · C, 6.17 · / · H, Found: 84.68 / · 'C, 6.45 · / · H.

C. Preparation of L- (4-cumene) -cyclooctene. A solution of 70 g of 4-bromocumene in about 250 ml of ether is added dropwise with stirring to a suspension of 8.75 g of magnesium turnings in 50 ml of ether, controlling the rate of addition to keep the mixture at a gentle boiling point. After completion of the dropwise addition, the mixture is stirred for 3 hours at room temperature, then a solution of 38 g of cyclooctanone in 250 ml of ether is added dropwise and the mixture is refluxed for about 12 hours. The resulting mixture is cooled to room temperature and decomposed by carefully adding 60 ml of saturated ammonium chloride solution.

The ether layer was separated from the solid which was washed with ether and benzene. The combined organic solutions are washed with dilute hydrochloric acid and water, dried over sodium sulfate and the solvents are evaporated off in vacuo. The residue was distilled under reduced pressure to give 25.1 g of L- (4-cumene) -cyclooctene, bp 128-140 ° C (0.1 mm Hg, n = 1.5459.

Product analysis.

Calculated for the formula CH-: 89.91 · / · C, 10.59 · / · H, Found: 89.46 · / · C, 10.77 · / H.

In an analogous manner, by using appropriate amounts of 4-bromocumene, magnesium and norcamphora, 2-hydrocyy-2-4-cumene) -norbonnane is obtained, boiling point 137-145 ° C / 0.1 mm Hg, containing traces of 2- (4). -nkumenyl) -2-norbornene.

Likewise, in an analogous manner, by using appropriate amounts of 4-bromocumene, propionaldehyde and magnesium, L- (4-kU'menyl) -propanol is obtained, boiling point 124-135 ° C / 5 mm Hg, n ** = 1.5789 .

Product analysis.

Calculated for formula C.₁₂H.₁₈O: 80.85 / · C, 10.18% H, 81.08% C, 9.92 / · H.

The compounds according to the invention, administered orally or parenterally in daily doses of 1 to 100 mg per kg of body weight, in humans and animals clearly reduce inflammation and the accompanying symptoms of swelling, redness, restriction of freedom of movement, pain and elevated body temperature.

These compounds are excellent anti-inflammatory agents that do not cause the side effects of gastric disorders that often occur with known agents. The table shows the values ​​of the lowest ED dose_M. effective when administered orally. These values, expressed in mg per kg body weight, were determined using the erythema inhibition test by the method of CV Winder et al., Archives Int. Pharmacodyn vol. 116, p. 261 (1958).

Table

<td>The meaning of the symbol At in the studied relationship</td><td>ED50 value mg / kg for oral administration</td>

<td>4- (ιl-cyclooctenyLo) - -phenyl</td><td> 25</td>

<td>4-cyclooctylphenyl</td><td> 5</td>

<td>4'-fluorpdiphenylyl</td><td> 50</td>

<td>4-2-norbonnyl) -phenyl</td><td> 100</td>

<td>3-methoxy-4-fenoky- phenyl</td><td> 15</td>

The compounds according to the invention are used in the treatment of inflammatory conditions, preferably in doses containing about 50 to 100 mg of at least one of these compounds and an appropriately known carrier. Orally administered compositions are preferably in the form of, for example, capsules or tablets. 4-phenylcumene has particularly valuable properties, but it can be partially or completely replaced by other compounds according to the invention.

Example I. A mixture of 21.2 g of 2- (4- &lt;1 -tutphenylyl) -propainol-2, 4 g of 5 · / · palladium on carbon, 20 drops of sulfuric acid and 200 ml of ethyl acetate is hydrated until the calculated volume of hydrogen has been absorbed, then the catalyst is filtered off and the filtrate is washed successively with water, 5 · / · sodium hydrogencarbonate solution and recharged, then dried and the solvent is evaporated in vacuo. He is given a judgment g of 4-fniyldkiumieinu oily consistency. The product boils at 199-112^aboutC / 9.09 mm of Hg, n t = 1.5899.

Product analysis. Calculated for the formula 91.78 · / · C, 8.22% H,

Found: 92.06 · / · C, 7.97 · / · H.

Example II. By proceeding analogously to that described in Example 1, but starting from 2-hydrdxy-2- (4-cuunenyl) -norboman, 4- {2-xortb: om: yo) -cumen is obtained, boiling point 150- 156^aboutG / 5 mm Hg, n⁴ = 1,5333.

Product analysis.

Calculated for the formula: CieHn: 89.65 · / · C, 10.35% H, Found: 89.38% C, 19.29% H.

Example III. In an analogous manner to that described in Example 1, 4- (4-fluorophenyl) -cumen is obtained from 2- {4'-fluoro-diienoyl) -prqpaanol-2, mp 91-94 ° C.

Product analysis.

Calculated for formula C.₁₅H.₁₅F:

84.08% C, 7.06% H, 8.86% F,

Found: 84.92% C, 6.92% H, 8.59% F,

Example IV. In an analogous manner to that described in Example 1, 4-cyclooctylocumene is obtained from 1- &lt;4 ° C-methyl) -cytene, boiling point 126-134 ° C / 9.1 mm Hg, n′i = 1.5239.

Product analysis.

Calculated for formula C._nH._M.: 88.62% C, 11.38% Ή, Found: 88.38% C, 11.5% H.

Example 5 A mixture of 21 g of 3-phenoxy-α-methylstyrene in 209 ml of ethanol is hydrogenated in the presence of 1 g of platinum oxide until the calculated volume of hydrogen has been absorbed, then the catalyst is filtered off and the solvent of the filtrate is evaporated under reduced pressure.

The oily residue was distilled under reduced pressure to give 17.1 g of 3-phenoxycumene, boiling point 140-150.^aboutC / 5 mm Hg, n ·· = 1.5574.

Product analysis.

Calculated for the formula CuHleO: 84.87% C, 7.69% H, Found: 84.82 · / · C, 7.51% H.