NO146322B - ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE STEEL BENDER DERIVATIVES - Google Patents

Description

The present invention relates to an analogue method for the production of new therapeutically active stilbene derivatives with the formula Q

where n = 1 or 2 and, if n = 1, R 1 and R < 2 > means hydrogen, lower alkoxy or halogen, or, if n = 2, R < 1 > means hydrogen, lower alkoxy or halogen and R < 2 > hydrogen, R <3 >R4, R5 and R6 hydrogen or lower alkyl, R7 hydrogen, 9 methyl or ethyl, R and R hydrogen, lower alkyl or halogen and R10 is a residue -(CH=CR<19>) R< 11>, where m is 0 11 m . or 1 and R a remainder

or the 2-oxazolinyl residue, or if m = 1, also hydro-12 13

gene, R hydrogen or lower alkyl, R . hydrogen, lower alkyl or a residue N(R<17>, R<18>) or -OR<14>, R14 hydrogen, lower alkyl or alkanoyl, R1^ hydrogen, lower alkyl or a residue -OR16 or -(CH2) pN(R17, R18), R16 hydrogen, lower alkyl, hydroxy-lower-alkyl, phenyl-lower-alkyl,

17 18 nitro-substituted phenyl lower alkyl, R and R hydrogen, lower alkyl or together with the nitrogen atom to which they are attached, a piperidino-, piperazino-, morpholino-, thiamorpho-19

lino- or pyrrolidino residue, R hydrogen or lower alkyl and p means 0, 1, 2 or 3, as well as ketals of compounds of formula I, in which R<11> is a residue -C(0)R<15> and R<15 > hydrogen or lower alkyl,

and salts of compounds of formula I.

The term "lower" used here denotes groups with up to 6 carbon atoms.

Alkyl and alkoxy groups can be branched or unbranched, such as methyl, ethyl, isopropyl or 2-methylpropyl, respectively methoxy, ethoxy or isopropoxy.

Alkanoyl groups are derived, e.g. from acetic, propionic or pivalic acid or also from the higher carboxylic acids with up to 20 carbon atoms, e.g. from palmitic or stearic acid.

Among the halogen atoms, chlorine and bromine are preferred.

A preferred group of compounds of formula I are those in which R <0> is hydroxymethyl, alkoxymethyl, alkanoyloxymethyl, carboxyl, alkoxycarbonyl, formyl, alkylenedioxymethyl, alkanoyl, carbamoyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, piperidino- , morpholino-, thiomorpholino-, pyrrolidinocarbonyl- or 2-oxazolinyl.

The compounds of formula I are obtained according to the invention by reacting a compound of the general formula

with a compound msd the general formula

wherein R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, R8, R9 and n have the above meaning, and either A is a triarylphosphonium alkyl group of formula R- CH-<p>[q]3<®> Y ®, where R denotes hydrogen, methyl or ethyl, Q an aryl residue and Y the anion of an organic or inorganic acid, and B is formyl, or A is formyl, acetyl or propionyl , and B is a dialkoxyphosphinylalkyl group of the formula R-CH-<p>Cz^,

0 in which Z denotes a lower carboxylic acid residue,

to a compound of the general formula I, and if reduced, the residue R10 functionally converts.

The aryl groups in the mentioned triarylphosphonium groups which are denoted by Q simply include all known aryl residues, but in particular mononuclear residues such as phenyl or lower-alkyl, respectively lower-alkoxy-substituted.phenyl, such as tolyl, xylyl, mesityl or p-methoxyphenyl.

Of the inorganic acid anions Y, the chlorine and bromine ion or the hydrosulphate ion are preferred, and of the organic acid anions tosyloxy ion.t..

The carboxylic acid residues denoted by Z in the dialkoxyphosphinyl alkyl group with the formula R-CH-P[z]9 are preferably lower

o carboxylic acid residues with 1-6 carbon atoms such as methoxy or ethoxy.

The starting compounds of formula II can, insofar as their preparation is not known or described in the following, be prepared analogously with known or in the subsequently described methods.

Compounds of formula II, in which A. is a formyl-, acetyl-

1 2

or propionyl group, and the substituents R and R hydrogen, [oxo compounds of formula II], are e.g. obtainable by subjecting a in the cyclopentene ring substituted indan corresponding to the desired final compound of formula I,

or a similarly substituted tetrahydronaphthalene in the cyclohexene ring in an acylation reaction. This can e.g.

happen in such a way that one acylates in - or tetrahydro-naphthalene derivative in the presence of a Lewis acid.

Suitable acylating agents are formaldehyde/hydrochloric acid, acetyl and propionyl halides, e.g. acetyl and propionyl chloride.

Of the Lewis acids, the halides of aluminium, such as aluminum trichloride, are preferred. The reaction is preferably carried out in a solvent such as nitrobenzene or in a chlorinated hydrocarbon such as methylene chloride. The reaction temperature is preferably 0 to approx. +5°C.

1 2

The obtained oxo compound of formula II, in which R and R are hydrogen, is condensed according to the invention with a phosphonate of formula III, in which B is a dialkoxyphosphinylmethyl-1 2

group to compounds of formula I in which R and R are hydrogen.

The necessary phosphonium salts of formula II in which A means

a 1-(triarylphosphonium)-methyl[ethyl or propyl] group for the condensation with an aldehyde of formula III, in which B is an oxo group, can be prepared, for example, as follows: The aforementioned obtained oxo compounds of formula II,

12

where R and R . means hydrogen, is reduced by approx. 0 to approx. +5°C using a complex metal hydride, e.g. with sodium borohydride in an alkanol or with lithium aluminum hydride in an ether, tetrahydrofuran or dioxane to the corresponding alcohol. The alcohol obtained is then halogenated in the presence of an amine base such as pyridine by means of a common halogenating agent, e.g. with phosphorus oxychloride or phosphorus tribromide. The halide obtained is then reacted with a triarylphosphine in a solvent, preferably with triphenylphosphine in toluene or xylene to give the desired phosphonium salt of formula II.

Oxo compounds and phosphonium salts of formula II, in which the substituents R 1 and R 2 are alkoxy or halogen, can e.g. is produced by converting the corresponding phenol in a manner known per se by treatment with an alkylating agent, e.g. by reaction with a lower alkyl halide or with a lower alkanol in the presence of an acidic agent to the corresponding alkoxy derivative of formula II.

The aforementioned phenols are e.g. available as follows: The oxo compound of formula II unsubstituted in the aromatic ring part is nitrated by treatment with a mixture of concentrated nitric acid and concentrated sulfuric acid. The nitro group, which preferably occurs in the o-position to the formyl, acetyl or propionyl group, is catalytically reduced in a manner known per se, e.g. by means of Raney nickel, to the amino group, which is converted through the diazonium salt in a known manner into the hydroxy group.

If the diazonium salt prepared from the amine is treated hot with a copper (I) halide, the corresponding halogen derivative of the oxo compound of formula II is obtained. Upon renewed treatment of the halogen derivative obtained with nitric acid, it is possible to introduce a nitro group in the m-position to the formyl, acetyl or propionyl group, which can likewise, as described above, be converted into hydroxy or halogen. By converting the hydroxy group into alkoxy, one obtains identically or mixed substituted derivatives of the starting ketones of formula II.

A halogen atom in the aromatic core can, if desired, be removed again by reduction in a manner known per se.

The compounds of formula III, in which B means formyl, can be prepared from nitro-substituted phenyl derivatives in the 1-position as described in Chem. Berichte: 102 (1969) at pages 2502-2507. They are also available through reduction of the corresponding p-carboxy substituted phenyl derivatives. The reduction of the carboxyl to formyl group can e.g. is carried out with di i sobutyl aluminum hydr id.

The condensation components of formula III, in which B is a dialkoxyphosphinylmethyl group, can be prepared from the aforementioned compounds of formula III, in which B means formyl in such a way that one uses a metal hydride, e.g. using sodium borohydride converts the formyl group into the hydroxymethyl group, halogenates this using a common halogenating agent, e.g. with phosphorus trichloride and reacts the halogen derivative obtained with a trialkyl phosphite, especially with triethyl phosphite to the desired phosphonate of formula III.

The condensation components of formula III, in which B means formyl or a di- hydroxyphosphinylmethyl group, are furthermore also available by halogenating the corresponding methyl-substituted phenyl derivative in the 1-position and reacting the resulting halomethyl derivative either with a trialkyl phosphite or hydrolyzing to the hydroxymethyl derivative and oxidizing this by treatment with an oxidizing agent , e.g. with manganese dioxide.

The conversion of the compounds of formula II and III can be carried out according to the known methods of Wittig, respectively. The Horner reaction. Preferably, such compounds of formula III are used as starting materials, in which R<1>"'" is not a reactive group towards phosphoranes, such as in particular the formyl group.

As a functional conversion of a substituent R<10> in a compound of formula I comes e.g. the conversion of a carboxyl group into a salt, an ester, an amide, an oxazoline derivative or into the hydroxymethyl group in question, which in turn can be esterified or etherified, and

the saponification of a carboxylic acid ester or its reduction to the hydroxymethyl group.

The hydroxymethyl group can also be oxidized to the formyl group. Compounds of formula I containing a formyl residue

can e.g. is converted by means of a Wittig reaction to compoundx of formula I, in which R<10> is a residue ~(CH=CR"<1>"<9>)m R ,

19 11

where m = 1, R H or alkyl and R e.g. alkoxymethyl, alkanoyloxymethyl, carboxyl, alkoxycarbonyl, alkanyl or alkenyl.

All these conversions can be carried out according to methods known per se.

In the Wittig reaction, the components react with each other in the presence of an acid-binding agent, e.g. in the presence of a strong base, such as butyllithium, sodium hydride or the sodium salt of dimethylsulfoxide, preferably however in the presence of an optionally lower alkyl substituted ethylene oxide such as 1,2-butylene oxide, optionally in a solvent, e.g. in an ether, such as diethyl ether or tetrahydrofuran, or in an aromatic hydrocarbon such as benzene in a temperature range between room temperature and the boiling point of the reaction mixture.

In the Horner reaction, the components are condensed with the aid of a base and preferably in the presence of an inert organic solvent, e.g. by means of sodium hydride in benzene, toluene, dimethylformamide, tetrahydrofuran, dioxane or 1,2-dimethoxyalkane, or also by means of a sodium alcoholate in an alkanol, e.g. sodium methylate in methanol, in a temperature range between 0° and the boiling point of the reaction mixture.

The. has also proven appropriate in certain cases

to link the aforementioned reactions to each other in situ, i.e. the condensation components without isolating the relevant phosphonium salt or phosphonate.

A carboxylic acid of formula I can be transferred in a manner known per se, e.g. by treatment with thionyl chloride, preferably in pyridine, or phosphorus trichloride in toluene in the acid chloride, which through reaction with alcohols can be converted into an ester and with amines into the corresponding amide. Amides can be converted in a manner known per se to amines, e.g. by reduction with complex metal hydrides such as LiAlH^. A carboxylic acid ester of formula I can be hydrolysed in a manner known per se, e.g. by treatment with alkalis, especially by treatment with aqueous alcoholic caustic soda or caustic soda in a temperature range that lies between room temperature and the boiling point of the reaction mixture and either through an acid halide or, as described above, immediately amidated.

A carboxylic acid ester of formula I can e.g. is converted with lithium amide directly to the corresponding amide. The lithium amide is advantageously brought to react with the appropriate ester at room temperature.

A carboxylic acid of formula I can further be converted through the halide by reaction with 2-aminoethanol or 2-amino-2-methyl-1-propanol and subsequent cyclization to an oxazoline derivative of formula I.

A carboxylic acid or a carboxylic acid ester of formula I

can be reduced in a manner known per se to the corresponding alcohol of formula I. The reduction is advantageously carried out using a metal hydride or alkyl metal hydride in an inert solvent. Suitable hydrides have above all been found to be mixed metal hydrides such as lithium aluminum hydride or bis-[methoxy-ethyleneoxy]-sodium aluminum hydride. Useful as solvents are i.a. ether, tetrahydrofuran or dioxane, when lithium aluminum hydride is used, and ether, hexane, benzene or toluene, when diisobutylaluminum hydride or bis-[methoxy-ethyleneoxy-sodium aluminum hydride is used.

An alcohol of formula I may be preferred, e.g. in the presence of

a base, preferably in the presence of sodium hydride, in an organic solvent such as dioxane, tetrahydrofuran, 1,2-dimethoxyethane, dimethylformamide, or also in the presence of an alkali metal alcoholate in an alkanol in a temperature range between 0° and room temperature with an alkyl halide, e.g. with methyl iodide.

An alcohol of formula I can also be esterified by treatment

with an alkanoyl halide or anhydride, suitably in the presence of a base, e.g. in the presence of pyridine or triethylamine in a temperature range between room temperature and the boiling point of the reaction mixture.

The carboxylic acids of formula I form salts with bases, especially with alkali metal hydroxides, preferably with sodium or potassium hydroxide.

The compounds of formula I are predominantly formed in trans form. Any cis-parts formed can, if desired, be separated from or isomerized to the trans-compounds in a manner known per se.

The process products of formula I are pharmacodynamically valuable compounds. They can find application for topical and systemic therapy of benign and malignant neoplasias, of premalignant lesions and furthermore also for systemic and topical prophylaxis of the aforementioned disorders.

They are also suitable for topical and systematic therapy of acne, psoriasis and other dermatoses with an increased or pathologically altered cornification incipient dermatoses as well as inflammatory and allergic dermatological problems. The process products with formula I can also be used to combat mucosal diseases with inflammatory or degenerative or metaplastic changes.

The new compounds differ from known retinoids in that they are effective in extremely small amounts.

The tumor-inhibiting effect of the process products is significant. In papilloma experiments on mice, a recurrence of tumors induced with dimethylbenzanthracene and croton oil is observed. The cross-section of the papillomas decreases over the course of 2 weeks with intraperitoneal application of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]- benzoic acid

ethyl ester

at 0.2 mg/kg/week with 75%

at 0.1 mg/kg/week with 56%

at 0.05 mg/kg/week with 48%.

Upon oral application of p-[(E)-2-(5,6,7,8-tetrahydro-5,5, 8, 8-tetramethyl-2-naphthyl)propenyl]-benzoic acid ethyl ester to mice, the cross-section of the induced tumors decreases in the course of 2 weeks

[5 single doses/week]

at 0.4 mg [5x0.08 mg]/kg/week with 63%

at 0.2 mg [5x0.04 mg]/kg/week with 48%

at 0.05 mg [5x0.01 mg]Ag/week with 3 7%.

The compounds of formula I and their salts can further be used for the oral treatment of rheumatic diseases, especially those of an inflamed and degenerative nature such as joints, muscles, tendons and other parts which attack the locomotor system. Examples of such diseases are primary-chronic polyarthritis, spondyl-arthritis ankylopoetica bechterew and arthropathy psoriatica.

Example 1

30.5 g [1-(1,1,3,3-tetramethyl-5-indanyl)ethyl]-triphenylphosphonium bromide and & g 4-ethoxycarbonyl-benzaldehyde are stirred after adding 300 ml of butylene oxide for 12 hours in an inert gas atmosphere at 65°C. The clear solution formed is stirred, then introduced for approx. 500 ml ice/water and extracted twice

with hexane. The organic extract is shaken three times with methanol/water, dried over sodium sulfate and evaporated under reduced pressure. The residue is purified by absorption on silica gel [eluent: hexane/ether 19:1]. The p-[(E)-2-(1,1,3,3-tetramethyl-5-indanyl)propenyl]-benzoic acid ethyl ester obtained from the eluate melts after recrystallization from ether/hexane at 70 - 71°C.

The [1-(1,1,3,3-tetramethyl-5-indanyl)ethyl]-triphenylphosphonium bromide used as starting material can e.g. is prepared as follows: 87.8 g of acetyl chloride are dissolved in 240 ml of nitrobenzene. 149.2 g of aluminum chloride are introduced in portions into the solution. The mixture is cooled to 0 - 5°C and is then mixed with strong cooling dropwise with a solution of 195.0 g of 1,1,3,3-tetramethyl-indane in 360 ml of nitrobenzene. The temperature must not exceed 5°C. The reaction mixture is stirred for 15 hours at 0°C, it is then introduced into 3 1 of ice/water and extracted with ether. The ether extract is washed twice with a 2N sodium hydroxide solution and twice with a saturated sodium hydroxide solution, dried over sodium sulfate and then evaporated first in a water jet vacuum and then to remove the nitrobenzene in a high vacuum. The residual oily (1,1,3,3-tetramethyl-5-indanyl)-methyl ketone boils at 100-103°C/0.5 Torr.

2.66 g of lithium aluminum hydride is mixed with 40 ml of absolute ether. While cooling to 0 - 5°C, drip over the course of 30 min. 26 g of 1,1,3,3-tetramethyl-5-indanyl-methyl-ketone.

After another 30 min. carefully mix the mixture dropwise with 25 ml of a saturated sodium sulphate solution. React—

the solution is filtered. The filtrate is washed once with a

In sodium hydroxide solution and twice with a saturated saline solution, dry over sodium sulfate and evaporate under reduced pressure to remove the solvent. The remaining oily oc-1,1,3,3-pentamethyl-5-indan-methanol, a thin-layer chromatographically uniform compound [eluent: hexane/ether 80:20], is further processed immediately as follows: 24.0 g oc-1, 1,3,3-pentamethyl-5-indan-methanol is dissolved in 20 ml of absolute ether and 100 ml of absolute hexane. The solution is mixed after adding 2 drops of pyridine at 0 - 5°C over the course of 30 minutes. dropwise with 16.2 g of phosphorus tribromide dissolved in 80 ml of absolute hexane. After a further hour of stirring at 0 - 5°C, the reaction product is introduced into ice/water and extracted to exhaustion with ether. The ether extract is washed twice with a saturated sodium bicarbonate solution and coke solution, dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The remaining oily 5-(1-bromomethyl)-1,1,3,3-tetramethyl-indane, a thin-layer chroma togra-fish uniform compound [eluent: hexane/ether 95:5], is further worked up immediately as follows: 26.3 g of triphenylphosphine are dissolved in 120 ml of xylene. The solution is mixed with 30.9 g of 5-(1-bromomethyl)-1,1,3,3-tetramethylindane dissolved in 60 ml of xylene. The mixture is heated with stirring to 100°C and remains at this temperature for 12 hours. The resulting viscous 1-(1,1,3,3-tetramethyl-5-indanyl)ethyl-triphenylphosphonium bromide, which crystallizes after grafting, melts after recrystallization from methylene chloride/toluene at 151 - 156°C (the crystals contain 0.3 equivalents of toluene ).

EXAMPLE 2

2.4 g of 1,1,3,3-tetramethyl-5-indanyl-methyl ketone as well as 3.4 g of 4-[(diethoxyphosphinyl)methyl]-benzoic acid ethyl ester are dissolved in 7 ml of dimethylformamide. The solution is added dropwise under argon at room temperature and with stirring a sodium ethanolate solution, prepared from 0.33 g of sodium and 7 ml of ethanol, and then stirred

after for 18 hours at 70°C. The reaction mixture is then introduced

in ice/water and extracted with ether. The ether extract is washed with a saturated sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure. The remaining p-[(E)-2-(1,1,3,3-tetramethyl-5-indanyl)propenyl]-benzoic acid ethyl ester, a brown oil, is purified by absorption on silica gel [eluent: hexane/ether 9:1 ]. The ester melts after recrystallization from hexane/ether at 70-71°C.

EXAMPLE 3

Analogously to the working method described in example 1, p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid ethyl ester, m.p. 90-91°, is obtained from [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide and 4-ethoxycarbonylbenzaldehyde.

The starting compound [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide is available in an analogous way as described in example 1 from 5 ,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthalene over (5,6,7,8-tetrahydro-5,5,-8,8-tetramethyl-2-naphthyl)methyl ketone, 5 ,6,7,8-tetrahydro-α-5,5,8,3-pentamethyl-2-naphthalene methanol, 2-(bromomethyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene .

EXAMPLE 4

Analogously to the method described in example 1, p-[(E)-2-(3-methoxy-5,6,7,3-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl ] -benzoic acid ethyl ester, m.p. 97-98°C, obtained from [1-(3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide and 4-ethoxycarbonyl-benzaldehyde .

The [1-(3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]triphenylphosphonium bromide used as starting compound is available in an analogous manner as described in example 1 from 3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene above (3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 -naphthyl)methyl ketone, over 3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalene-methanol, over 2-(1-bromomethyl)-3-methoxy -5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthalene.

EXAMPLE 5

Analogous to the method described in example 1, p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-2-methyl- the benzoic acid ethyl ester as a colorless thin-layer chromatographic uniform oil, (Rf = 0.6; hexane/15% ether) from [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) ethyl]-triphenylphosphonium bromide and 3-methyl-4-ethoxycarbonyl-benzaldehyde.

The 3-methyl-4-ethoxycarbonyl-benzaldehyde used as condensation component can, starting from 4-nitro-3-methyl-benzoic acid, be prepared in an analogous manner to the preparation of 2-methyl-4-ethoxycarbonyl-benzaldehyde according to Huneck et al , in Chem. Pray. 102, 2502-2507 (1969).

EXAMPLE 6

Analogous to the working method described in example 1, the p-[(E)-2-(1,1,2,3,3-pentamethyl-5-indanyl)propenyl]-benzoic acid ethyl ester m.p. 79-80°C, is obtained from [1-(1,1,2,3,3-pentamethyl-5-indanyl)-ethyl]-triphenylphosphonium bromide and 4-ethoxycarbonyl.1-benzaldehyde.

EXAMPLE 7

Analogously to the working method described in example 1, the β-1(E)-2-(7-methoxy-1,1,3,3-tetramethyl-5-indanyl)propenyl]-benzoic acid ethyl ester, m.p. 72-73°C, is obtained from [1-(7-methoxy-1,1,3,3-tetramethyl-5-indanyl)ethyl]-triphenylphosphonium bromide and 4-ethoxycarbonyl-benzaldehyde.

The [1-(7-methoxy-1,1,3,3-tetramethyl-5-indanyl)ethyl]-triphenylphosphonium bromide used as starting compound can e.g. is prepared as follows: 84.3 g of (1,1,3,3-tetramethyl-5-indanyl)-methyl ketone (Example 1) is dissolved in 160 ml of concentrated sulfuric acid and cooled to -20°C. At this temperature, nitric acid, prepared from 40 ml of concentrated nitric acid and 80 ml of concentrated sulfuric acid, is added within 10 minutes. After the addition is complete, the thick porridge is immediately poured onto ice and extracted twice with ether. The ether extract is washed with a sodium bicarbonate solution and a sodium bicarbonate solution, dried over sodium sulfate and freed from the solvent under reduced pressure. The precipitated (6-nitro-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone melts after recrystallization from ether/hexane at 111-112°C.

75.8 g of (6-nitro-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone are dissolved in 1500 ml of methanol and hydrogenated under nitrogen with the aid of 20 g of Raney nickel for 48 hours at 45°C. 15 liters of hydrogen are taken up. The reaction solution is then filtered through. Speedex and the solvent are removed under reduced pressure. The precipitated (6-aminyl,1,3,3-tetramethyl-5-indanyl)-methyl ketone melts after the recrystallization from ether/hexane at 161-162°C.

113.1 g of (6-amino-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone are suspended in 2260 ml of 20% hydrochloric acid and cooled to 0-5°C. A solution of 33.9 sodium nitrite in 115 ml of water is added dropwise over the course of 10 minutes to the cold mixture and stirred for 30 minutes. The cold reaction solution is then added dropwise

during 2 hours with stirring in a solution of 243.2 g of copper(I) chloride in 250 ml of water and 250 ml of concentrated sarctic acid, which has been heated to 40-45°C. The reaction mixture is then cooled, introduced into ice water and drawn out three times with methylene chloride. The organic extract is washed with a sodium chloride solution, dried over sodium sulfate and freed from the solvent under reduced pressure. The residue is purified by adsorption on silica gel [eluent hexane/acetone 19:1]. The eluate obtained (6-chloro- 1,1,3,3-tetramethyl-5-indanyl)-methyl ketone melts after the recrystallization from hexane/ether at 69-71°C.

Analogously to the method described above, the (6-chloro-7-nitro-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone, m.p. Ii9- • 120°C, is obtained from (6-chloro-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone, and (6-chloro-7-amino-1,1,3,3 -tetramethyl-5-indanyl)-methyl-ketone, m.p. 116-117°C, from (6-chloro-7-nitro-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone.

21.1 g of (6-chloro-7-amino-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone is introduced into 48 ml of concentrated sulfuric acid and, after heating to 50°C, is added slowly with 140 ml of distilled water. Add dropwise to the mixture after cooling to 0-5°C in the course

of 45 minutes a solution of 5.5 g of sodium nitrite in 20 ml of water. The obtained cold reaction mixture is added dropwise while stirring and

during 2 hours a solution of 60 ml of water and 60 ml of concentrated sulfuric acid held at 70°C. The mixture is cooled, then ice water is introduced and extracted three times with ether. The organic phase is washed with a sodium chloride solution, dried over sodium sulfate and freed from the solvent under reduced pressure. The residue is purified by adsorption on silica gel [eluent hexane/ether 19:1], The (6-chloro-7-hydroxy-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone obtained from the eluate melts after the recrystallization from hexane/ether at 78-80°C.

4.4 g of (6-chloro-7-hydroxy-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone are dissolved in 10 ml of dimethylformamide. First, 1.1 g of potassium hydroxide (dissolved in 1.2 ml of water) is added to the solution, then 5.5 ml of methyl iodide and then stirred for 3 hours at room temperature. The reaction mixture is then introduced into ice water and extracted

twice with ether. The organic extract is washed several times with a sodium chloride solution, dried over sodium sulphate and freed from the solvent under reduced pressure. The precipitated (6-chloro-7-methoxy-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone melts after recrystallization at 59-60°C.

25 g of (6-chloro-7-methoxy-1,1,3,3-tetramethyl-5-indanyl)-methyl-

ketone dissolves in approx. 200 ml of methanol and hydrogenated after adding 10 g of triethylamine and 2.5 g of 5Vig palladium/carbon catalyst at room temperature. Within 5 hours, a mole equivalent of hydrogen is absorbed. The reaction solution is filtered over "Speedex". The filtrate is evaporated. The residue is dissolved in water/ether and extracted several times with ether. The organic extract is washed with sodium chloride solution, dried over sodium sulphate and freed from the solvent under reduced pressure. The precipitated (7-methoxy-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone melts after recrystallization from hexane at 76-77°C.

Analogously to the working method described in example 1, [1-(7-methoxy-1,1,3,3-tetramethyl-5-indanyl)ethyl]-triphenylphosphonium bromide, m.p. 209-210°C, is prepared from (7-methoxy-1,1,3,3-tetramethyl-5-indanyl)-methyl ketone over 7-methoxy-α-1,1,3,3-pentamethyl-5-indan -methanol, over 5-(1-bromomethyl-7-methoxy-1,1,3,3-tetramethyl-indane).

EXAMPLE 8

Analogous to the working method described in example 1, p-..[. The (E>-2-(1,1,3,3-tetramethyl-5-indanyl)vinyl]-benzoic acid ethyl ester, m.p. 151-152°C, is obtained from [(1,1,3,3-tetramethyl-5 -indanyl)methyl]-triphenylphosphonium chloride and 4-ethoxycarbonylbenzaldehyde.

The [(1,1,3,3-tetramethyl-5-indan-yl)methyl]-triphenylphosphonium chloride used as starting compound can e.g. f is represented as , . ;. follows: 34.2 g of 1,1,3,3-tetramethyl-indan, 150 ml of glacial acetic acid, 300 ml of concentrated hydrochloric acid and 77 ml of formaldehyde solution (35%) are heated, at • room temperature with stirring for 2 more hours. 75-78°C.. Then •. a further 7.7 ml of 35% formaldehyde solution is added dropwise over the course of 10 minutes. The react ion mixture is kept in '. 15 hours at the same temperature, then cooled, introduced for approx. 1 liter of ice water and extracted exhaustively with toluene; The organic phase is washed neutral with water, dried over sodium sulphate and ■ evaporated under reduced pressure. The crude product obtained, a reddish oil, is distilled over a Vigreux column. The pure 5-chloro-methyl-1,1,3,3-tetramethyl-indane boils at 143-146°C/19 mm Hg.

Analogous to the method described in example 1, [1-(1,1,3,3-tetramethyl-5-indanyl)methyl]-triphenylphosphonium chloride can be obtained from 5-chloromethyl-1,1,3,3-tetramethyl-indan and triphenylphosphine .

EXAMPLE 9

Analogous to the working method described in example 1, the 4'-[(E)-2-(1,1,3,3-tetramethyl-5-indanyl)propenyl]-acetophenone, m.p. 130-131°C, is obtained from [1-(1,1,3,3-tetramethyl-5-indanyl)ethyl]-triphenylphosphonium bromide and 4-acetyl-benzaldehyde.

EXAMPLE 10

49 g of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]-benzoic acid ethyl ester (Example 3) are dissolved in 500 ml of ethanol at 45°C and is mixed dropwise with stirring with a solution of 20 g of potassium hydroxide in 50 ml of water. The mixture is stirred for 18 hours at 55°C, then cooled, introduced into ice/water, acidified with 3N sulfuric acid to pH 2 and extracted twice with methylene chloride. The methylene chloride extract is washed with a saturated saline solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The remaining p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid melts after the recrystallization from methylene chloride/hexane at 24 7 -248°C.

EXAMPLE 11

To a suspension of 7.0 g of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid (Example 10) in 40 ml of absolute ether, 3.5 ml of thionyl chloride are added dropwise after adding 1.8 ml of pyridine while stirring at 0-5°C. After adding 5 drops of N,N-dimethylformamide, the reaction solution is heated to room temperature, stirred for 18 hours and then decanted. The clear yellow acid chloride solution is introduced dropwise into a solution of 3 ml of ethylamine in 20 ml of absolute ether. The mixture is then stirred for 2 hours at room temperature, then introduced into a saturated sodium chloride solution and extracted twice with ether. The ether extract is washed with a saturated sodium chloride solution, dried over anhydrous sodium sulphate and evaporated under reduced pressure. The remaining p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid monoethylamide melts after the recrystallization from methylene chloride/hexane at 177-178.5°C.

EXAMPLE 12

11.3 g p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]-benzoic acid ethyl ester (Example 3) dissolved in 20 ml of absolute ether and 20 ml of absolute tetrahydrofuran are introduced dropwise at 0-5°C into a slurry of 1.33 g of lithium aluminum hydride in 20 ml of absolute ether. The reaction solution is stirred for 12 hours under inert gas at room temperature, then added dropwise at 0-5°C

5 ml of a saturated sodium sulfate solution and filter over "Speedex". The filtrate is diluted with ether and washed once with a saturated sodium bicarbonate solution and twice with a saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated under reduced pressure. The precipitated p- [ (E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzyl alcohol melts after the recrystallization from methanol/ether at 123- 124°C.

EXAMPLE 13

To a suspension of 6.6 g of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzyl alcohol (Example 12) in 10

ml of ether and 10 ml of pyridine are introduced dropwise at approx. 5°C with stirring 5.8 ml acetyl chloride. The reaction mixture is stirred for 3 hours at room temperature, then it is introduced for approx. 100 ml of ice/water and extracted three times with ether. The ether extract is waxed once with 1 N hydrochloric acid, then three times with a saturated sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure.

The precipitated p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzyl acetate melts after the recrystallization from ether at 100-101° C.

EXAMPLE 14

5.0 g p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]-benzyl alcohol (Example 12), dissolved in 25 ml of dimethylformamide are introduced into a solution of 0.4 g of sodium hydride in 10 ml of dimethylformamide. After stirring for 1 hour at room temperature, 4.3 g of methyl iodide is added to the mixture and stirred for a further 2 hours. The reaction solution is then poured into approx. 200 ml of ice water and extracted three times with ether. The ether extract is washed three times with a saturated sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The precipitated p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzyl methyl ether melts after the recrystallization from ether at 55-56° C.

EXAMPLE 15

3.48 g of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]-benzoic acid (Example 10) is suspended in 12 ml of toluene. The suspension is stirred after the addition of 3.57 g of thionyl chloride for 12 hours at 50° and then evaporated under reduced pressure to dryness. The residue is dissolved in 6 ml of methylene chloride. The solution is introduced dropwise at 0°C into a solution of 2.3 g of 2-amino-2-methyl-1-propanol in 6 ml of methylene chloride. - The white suspension is stirred for 2 1/2 hours at room temperature, diluted with vinegar, washed

three times with water, dried over sodium sulfate and concentrated under reduced pressure. The white crystalline residue is suspended in 20 ml of ether and 6 g of thionyl chloride are added dropwise at 0°C. The white suspension is stirred for 30 minutes at room temperature and a saturated sodium carbonate solution is then carefully added until the pH value is 9. The now clear solution is diluted with ether. The ether phase is washed three times with a saturated sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure. The remaining 2-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]phenyl]-4,4-dimethyl- 2-oxazoline melts after recrystallization from ether at 115-116°C.

EXAMPLE 16

Analogously to the working method described in example 1, p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-butenyl]-benzoic acid ethyl ester can , m.p. 82-83°C is obtained from [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propyl]-triphenylphosphonium bromide and 4-methoxycarbonyl-benzaldehyde.

The [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propyl]-triphenylphosphonium bromide used as starting compound can be obtained in an analogous manner to that described in example 1 by starting from 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthalene and propionic acid chloride.

EXAMPLE 17

Analogous to the working method described in example 11, the p-[(E)-2-(5,6,7,8-tetrahydro-5,5,3,3-tetramethyl-2-naphthyl)propenyl]-benzoic acid diethylamide , m.p. 111-112°C, is obtained from p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid and diethylamine.

EXAMPLE 18

Analogously to the working method described in example 1, the p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,3-tetramethyl-2-naphthyl)propenyl]-benzoic acid morpholide, m.p. 143-144°C, is obtained from p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid and morpholine.

EXAMPLE 19

Analogous to the working method described in example 11, the p-[(.E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid isopropyl ester , m.p. 119-120°C, is obtained from p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid and isopropanol.

EXAMPLE 20

Analogous to the working method described in example 11, p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid-(2 )-diethylaminoethyl ester, m.p. 65-66°C is obtained from p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid and 2- diethylamino-ethanol.

EXAMPLE 21

6.7 g of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]-benzyl alcohol (Example 12) dissolved in 100 ml of absolute ether is added dropwise over 10 minutes to a stirred, cooled to 0-5°C slurry of manganese dioxide in 100 ml of absolute ether. Stir overnight at room temperature and then filter over "Celite". The filtrate is concentrated to dryness on a rotary evaporator. The yellowish oil crystallizes. Recrystallization from ether gives the p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]benzaldehyde as colorless crystals with m.p. 140-141°C.

EXAMPLE 22

Analogously to the working method described in example 1, the 4'-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) propenyl]-aceto-phenone , m.p. 148-149°C, is obtained from [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide and 4-acetyl-benzaldehyde.

EXAMPLE 2 3

3.0 g of 4'-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]-acetophenone (Example 22) dissolved in A catalytic amount of p-toluenesulfonic acid and 0.6 g of ethylene glycol are added to 40 ml of benzene and heated in a Dean-Stark apparatus, whereby the water formed is continuously separated. After 2 days of reflux heating

ning is cooled, introduced into ice/saturated sodium bicarbonate solution and extracted exhaustively with ether. The ether extract is washed twice with a saturated sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure to remove the solvent. The oily residue is purified by absorption on silica gel (eluent: hexane/ether 9:1). The 2-methyl-2-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-phenyl/ -1,3-dioxolane melts after recrystallization from ether at 122-123°C.

EXAMPLE 2 4

To 10.4 g of 4'-[(E)-2-(5,6,7,3-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-acetophenone (Example 22) dissolved in 100 ml of absolute methanol is carefully added at 0-5°C in portions to 1.0 g of sodium borohydride. The reaction solution is stirred for 1 hour at 0° and 2 hours at room temperature and is then poured into ice/water and extracted exhaustively with ether. The ether solution is washed twice with a saturated sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The precipitated α-methyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,3,8-tetramethyl-2-naphthyl)propenyl]-benzyl alcohol melts after crystallization from ether at 121-123°C.

EXAMPLE 25

Analogous to the method described in example 14, 1,2,3,4-tetrahydro-6-[(E)-p-(1-methoxyethyl)-α-methylstyryl]-1,1,4,4-tetramethylnaphthalene , m.p. 88-89°C, obtained from α-methyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzyl alcohol .

EXAMPLE 2 6

Analogous to the method described in example 13, α-methyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl ]-benzyl acetate, m.p. 85-86°C, obtained from α-methyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzyl alcohol .

EXAMPLE 2 7

Analogous to the working method described in example 1, 6-[(E)-p,a-dimethylstyryl]-1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalene, m.p. 84-85°C, is obtained from [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide and 4-methylbenzaldehyde.

EXAMPLE 2 8

Analogous to the working method described in example 1, 6-[(E)-p-isopropyl-α-methylstyryl]-1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-naphthalene, m.p. 86-37°C, is obtained from [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide and 4-isopropyl-benzaldehyde.

EXAMPLE 29

Analogously to the method described in example 1, 6-[(E)-α,2,4-trimethylstyryl]-1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalene, m.p. 54-56°C, is obtained from [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide and 2,4-dimethylbenzaldehyde.

EXAMPLE 30

Analogously to the working method described in example 1, but preferably with an extended reaction time, 1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-t(E)-a-methyl-p-vinylstyryl] -naphthalene, m.p. 94-95°C, is obtained from methyl-triphenylphosphonium bromide and p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzaldehyde (Example 21).

EXAMPLE 31

Analogously to the working method described in example 1, but preferably with an extended reaction time, 1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-[(E)-a-methyl-p-allylstyryl] naphthalene, m.p. 64-66°C, obtained from ethyl triphenylphosphonium bromide and p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzaldehyde (Example 21).

EXAMPLE 32

2 g of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl]-benzaldehyde (Example 21) and 1.4 g diethylphosphonic acid ethyl ester is dissolved in 5 ml of dimethylformamide. While stirring, a sodium alcoholate solution (prepared with 6.16 g of sodium in 3 ml of absolute alcohol) is added thereto at room temperature. After stirring for 18 hours at room temperature, the reaction mixture is poured onto ice-cold IN hydrochloric acid and extracted exhaustively with ether. The ether phases are washed with saturated sodium bicarbonate solution and sodium chloride solution and concentrated after drying over anhydrous sodium sulfate under reduced pressure. The residue is purified by adsorption on silica gel (eluent: hexane/ether 19:1). The (E)-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-cinnamic acid ethyl ester obtained from the eluate melts after recrystallization from hexane/ether at 126-127°C.

EXAMPLE 3 3

Analogous to the working method described in example 11, the p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid benzyl ester, m.p. 113-114°C, is obtained from p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl).propenyl]-benzoic acid and benzyl chloride.

EXAMPLE 34

Analogous to the working method described in example 11, 4-nitro-benzyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl )propenyl]-benzoate, m.p. 183-184°C, is obtained from p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid and 4-nitro -benzaldehyde.

EXAMPLE 35

Analogous to the method described in example 11, 2-hydroxyethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl ]-benzoate, m.p. 138-139°C, obtained from p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid and methylene glycol.

EXAMPLE 36

To a solution of 14.1 g of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-(E)-cinnamic acid ethyl ester (example 32) in 70 ml of absolute hexane is added dropwise at room temperature under an inert gas atmosphere and stirring 60 ml of a 20% solution of "Dibah" (dibutyl aluminum hydride) in hexane and stirred further overnight. The reaction solution is then added dropwise at 0-5°C to 50 ml of methanol and filtered over "Speedex". The filtrate is diluted with ether, washed once with a saturated sodium bicarbonate solution and twice with a saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated under reduced pressure. The precipitated 3-p-/[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]phenyl/-(E)-2- propen-l-ol melts after recrystallization from hexane at 109-110°C.

EXAMPLE 37

Analogous to the working method described in example 13, 3-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-phenyl/ -(E)-2-propen-1-yl acetate, m.p. 109-110°C, is obtained starting from 3-p-/[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl ]phenyl/-2-propan-1-ol.

EXAMPLE 38

Analogously to the working method described in example 14, 3-p-/[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl ] phenyl/-2-propen-1-yl-methyl ether, m.p. 88-90°C, is obtained starting from 3-p-/[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl ]phenyl/-(E)-2-propen-1-ol.

Claims (4)

<!>• Analogous procedure for the preparation of therapeutically active stilbene derivatives of the formula: 1 2 where n = 1 or 2, and, if n = 1 means R and R are hydrogen, lower alkoxy or halogen, or if n = 2, R1 means hydrogen, lower alkoxy or halogen and R2 hydrogen, R3, R4, R^ and R^ hydrogen or 7 8 lower alkyl, R hydrogen, methyl or ethyl, R and 9 10 R hydrogen, lower alkyl or halogen and R means a residue -(CH =CR 19 ) R 11, where m is 0 or 1 11 m oa R a remainder or the 2-oxazolinyl residue, or if m = 1 also 12 13 hydrogen, R hydrogen or lower alkyl, R hydro-17 18 gen, lower alkyl or a residue N(R , R ), or 14 14 -OR , R hydrogen, lower alkyl or alkanoyl, R<1>^ hydrogen, lower alkyl or a residue -OR"^ or -(CH2)pN(R17,R18), R16 hydrogen, lower alkyl hydroxy-lower-alkyl, phenyl-lower-alkyl, nitrosub-17 18 substituted phenyl lower alkyl, R and R hydrogen, lower alkyl or together with the nitrogen atom to which they are attached to a piperidino, piperazino, morpholino, thiamorpholino or pyrrolidino residue, R 19 hydrogen or lower alkyl and p is 0, 1, 2 or 3, as well as ketals of compounds, of formula I, where R is a residue -C(0)R'*'^ and R<1>^ hydrogen or lower alkyl, and salts of compounds of formula I, characterized in that one reacts a compound with the general formula with a compound of the general formula in which R,R,R,R,R,R,R, R, r<1>^ and n have the above meaning, and either A is a triarylphosphonium alkyl group of the formula R-CH-P [oJ3 ® Y ®, where R denotes hydrogen, methyl or ethyl, Q an aryl residue and Y the anion of an organic or inorganic acid and B is formyl, or A is formyl, acetyl or propionyl, and B a dialkoxyphosphinylalkyl group of the formula R-CH -p[z]_ • ir 0 where Z denotes a lower alkoxy acid residue, to a compound of the general formula I, and if desired, the residue R<10> functionally converts. 2. Method according to claim 1, characterized in that a starting material is used where R<1>^ denotes hydroxymethyl, alkoxymethyl, alkanoyloxymethyl, carboxyl, alkoxycarbonyl, formyl, alkylenedioxymethyl, alkanoyl, carbamoyl, mono-loweralkyl-carbamoyl, di-loweralkyl-carbamoyl , piperidino-, morpholino-, thiomorpholino-, pyrrolidinocarbonyl or 2-oxazolinyl. 3. Process according to claim 1 in the preparation of p-[(E)-2-(3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]- benzoic acid ethyl ester characterized by 12 5 6 that starting compounds are used in which R , R , R , R , 8 9 3 4 7 11 R and R are hydrogen, R , R and R are methyl, R carbethoxy and n means 2. 4. Method according to claim 1 in the preparation of p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzyl methyl ether characterized in that 1 2 5 6 8 9 starting compounds are used in which R , R , R , R , R and R are hydrogen, R<3>, R<4> and R<7> are methyl, R<11> carbethoxy and n means 2 , reduces the obtained p-[(E)-2-(3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid ethyl ester to the corresponding benzyl alcohol and methylates this.