CS216504B2 - Method of making the derivatives of the 3-+l 2-hydroxy-4-subst.phenyl+p-cycloalcanons and cycloalkanoles - Google Patents

Abstract

The invention relates to a process for the preparation of derivatives 3- (2-hydroxy-4-substitutedphenyl) cycloalkanones and cycloalkanols of the general formula cleavage of the phenolic hydroxyl protecting group function from the corresponding compound in a known manner.

Description

The present invention relates to a process for the preparation of certain cycloalkanones, cycloalkanols and their unsaturated derivatives of 5 to 8 carbon atoms in the cycloalkyl ring, containing in the 3-position a 2-hydroxy-4- (ZW-substituted) phenyl group, wherein Z represents an alkylene group of 1 to 13 carbon atoms or a radical of formula

- (alki) _m -O- (alk ₂ ) _n - in which each of the symbols man has a value of 0 or 1 and each of the symbols (alkij and (alkka)) represents an alkylene group having 1 to 13 carbon atoms, provided that: the sum of the carbon atoms in the residues (alki + (alk)) is not more than 13 and W represents a hydrogen atom, a phenyl group, a chlorophenyl group, a fluorophenyl group or a pyridyl group.

The above products are useful as central nervous system agents, in particular as analgesics, tranquilizing agents, sedatives and anti-anxiety agents in mammals, including humans, and / or as anticonvulsants, diuretics, and antidiarrheal agents for mammals, including humans.

Although a number of analgesics are currently available, there is a continuing search for new and better formulations, as there is no agent suitable for the treatment of a wide range of pain conditions, which at the same time has minimal side effects. The most commonly used substance, aspirin, is of no practical significance for the treatment of major pain and, moreover, is known to exhibit various undesirable side effects. Other analgesics such as d-propoxyphene, codeine and morphine are addictive. This clearly implies a need for a better and more effective analgesic.

U.S. Patent 3,576,887 (Apr 27, 71) discloses a series of 1- (1'-hydroxy) alkyl-2-o-hydroxyphenylcyclohexane and -cyclohexene derivatives as intermediates for the preparation of 6,6-dialkyltetrahydro- and hexahydrodibenzo [b, d] pyranes, which can be used as central nervous system depressants.

It has now been found that certain cycloalkanones, cycloalkanols and their unsaturated derivatives containing a 2-hydroxy-4-substituted phenyl group at the 3-position (see Formula I below) are effective as agents for influencing the central nervous system, particularly as analgesics. , tranquilizing agents, sedatives, and anti-anxiety agents in mammals, including humans, and / or as anticonvulsants, diuretics, and antidiarrheal agents for mammals, including humans. The invention also relates to various derivatives of these compounds which are useful as dosage forms of these compounds, as well as intermediates for the preparation of compounds of formula I, including processes for their preparation.

The compounds produced by the process according to the invention correspond to the general formula I,

in which

R is a saturated or unsaturated cycloalkyl radical selected from the group consisting of radicals of formulas I-A, II-A, I-B, II-B, I-C, II-C, I-D, and II-D,

(I-AJ (II-A)

il-B) (11-8 / (I-Cl (II-C))

(1-D) (II-D) in which the dotted line represents an optional double bond at any of the indicated positions, wherein in the case of the presence of a double bond, the remainder of R3 cannot be present,

A represents a hydrogen atom and

B is hydroxy, hydroxymethyl or C 1 -C 5 alkanoyloxy (Formula I), or

A and B together (formula II series) form an oxo, methylene or C 2 -C 4 alkylenedioxy group,

R 1 represents a hydrogen atom,

R 2 represents a hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 6 alkenyl group, a phenyl group or a C 1 -C 4 phenylalkyl group in the alkyl moiety,

R 5 represents a hydrogen atom or a methyl group,

R1 represents a hydrogen atom or a C1-C6 alkyl group, provided that when R5 represents a methyl group, R1 represents a hydrogen atom,

Z is C 1 -C 13 alkylene or a radical of formula

- (alk) _m -O- (alk _{2 n} j -, wherein (alk) and (alkzj are each an alkylene group having 1 to 13 carbon atoms, with the proviso that the sum of carbon atoms in (alk) + (alkz) is not greater than 13 aman each have a value of 0 or 1; and

W represents a hydrogen atom, a pyridyl group or a radical of formula wherein W 1 represents a hydrogen, fluorine or chlorine atom.

The invention also includes pharmaceutically acceptable acid addition salts of those compounds of formula I which contain basic groups. Typical examples of such compounds are those in which W represents a pyridyl group. Of course, in the case of compounds containing two basic groups, acid addition salts with several acids are possible. Representative examples of the above-mentioned pharmaceutically acceptable acid addition salts include salts with mineral acids such as hydrochlorides, hydrobromides, sulfates, phosphates and nitrates, salts with organic acids such as citrates, acetates, sulfosalicylates, tartrates, glycolates, malic acid salts, malonates, maleates, pamoates, salicylates, stearates, phthalates, succinates, gluconates, 2-hydroxy-3-naphthoates, lactates, mandelic acid salts and methanesulfonates.

Compounds of the invention which, in the meaning of R, contain radicals of formulas II-A to II-D, in which A and B together form an oxo group and R 1 represents a hydrogen atom, exist in solution in equilibrium with their hemiketalic forms. Both keto forms and hemiketal forms of such compounds of formula I are within the scope of the invention.

Compounds of the invention containing radicals IA to ID, in which A represents a hydrogen atom and B represents a hydroxyl group, contain centers of asymmetry at positions 1, 3 and 4 and, in the case of a cycloalkyl radical, and, of course, may contain other asymmetric centers in the substituents at positions 4 and 5 and in the -ZW moiety on the phenyl ring. Due to the quantitatively higher biological activity, the cis-arrangement between the substituent at the 1-position of the cycloalkyl ring and the phenolic or substituted phenolic residue at the 3-position, and the trans-arrangement between the substituents at positions 3 and 4 and the substituents at positions 4 and 5 on the cycloalkyl ring are preferred. For the same reason, the trans-arrangement between the substituents at positions 3 and 4 is also preferred for compounds containing the radicals of formulas IIA to IID, in which A and B together form an oxo group.

For the sake of simplicity, the above formulas refer to racemic compounds, but it is to be understood that racemic mixtures of the respective compounds, mixtures of diastereomers as well as pure enantiomers and diastereomers are also meant to be included. The usefulness of racemic mixtures, mixtures of diastereomers as well as pure enantiomers and diastereomers is determined by their biological activity as determined by the procedures described below.

Because of their greater biological activity over the other compounds described herein, those compounds in which R is one of the groups of formulas IA-ID and IIA-IID, wherein one of A and B is hydrogen and the other hydroxyl group, are preferred, respectively. in which A and B together form an oxo group, R 2 represents a hydrogen atom or an alkyl group as defined above, R 1 represents a hydrogen atom or an alkanoyl group as defined above, R 1 represents a hydrogen atom or an alkyl group as defined above, and Z and W have the following meanings:

C 8 -C 11 alkylene - C 4 -C 7 alkylene - (alki-O- (alk ₂ ) _n · 0 (alk-O- [alk ₂ ) _n 0 hydrogen

pyridyl hydrogen

Particularly preferred compounds of the formula I, in particular the saturated cycloalkyl derivatives of the formula I, are those mentioned above in which:

R 1 and R 5 are hydrogen atoms,

Z is —C (CH3) 2 (CH2) 6 and W is hydrogen,

Z is C 4 -C 7 alkylene and W is phenyl,

Z is -O-alkylene of 7 to 9 carbon atoms and W is hydrogen,

Z represents a C 4 -C 5 -alkylene group and W represents a phenyl group,

A is hydrogen and B is hydroxy (cis- and trans-formyl,

A and B together form an oxo group,

Ra represents a hydrogen atom, a methyl, propyl or propenyl group,

R 5 represents a hydrogen atom and

R4 represents a hydrogen atom or a methyl group.

Particularly preferred are saturated cycloalkyl derivatives containing radicals of formulas IB and IC, in which R 1, R a, R 5, R 1, Z and W have any of the meanings given above for the preferred compounds and A and B independently of one another hydrogen or hydrogen. hydroxyl group.

With respect to analgesic activity, particularly preferred compounds from the group of the above-mentioned preferred compounds are those in which Ra represents a methyl, propyl or propenyl group and R3 and R4 represent hydrogen atoms.

The saturated cycloalkyl derivatives of the formula I according to the invention, in which R 5 represents a hydrogen atom, are prepared from the corresponding 2-bromo-5- (Z-W-substituted) phenol by a series of reactions comprising the first step of protecting the phenolic hydroxyl by introducing a protecting group Q.

Suitable protecting groups are those which do not interfere with the subsequent reactions and which can be removed under conditions that do not lead to undesired reactions at other sites of the above compounds or products thereof. Representative examples of such Q-protecting groups include methyl, ethyl, benzyl, or substituted benzyl, with, for example, C 1 -C 4 alkyl, halogen (fluoro, chloro, bromo, or iodo). or C1-C4alkoxy.

Our related patents 216,502, 216,505, 216,506 describe various methods for converting the aforementioned protected 2-bromo-5- (Z-W-substituted-phenol) to a compound of formula

in which

A, B, R a, R 3, R 4, Z, W and n are as defined above and a

Q represents the aforementioned protecting group.

These compounds are used as starting materials in the process according to the invention by removing the above protecting group Q to release the hydroxyl group at the 2-position of the aryl radical.

Ether protecting groups can be cleaved using hydrobromic acid in acetic acid or by treatment with 48% aqueous hydrobromic acid. The reaction is carried out at an elevated temperature, preferably at reflux. However, when Z represents a residue

- (alk) -O- (alk ₂ ) _n -, acids such as polyphosphoric or trifluoroacetic acid must be used to prevent cleavage of the ether bond and other reagents may be used to remove ether protecting groups such as methyl or ethyl groups, If the protecting groups are benzyl or substituted benzyl groups, such groups can be cleaved by catalytic hydrogenolysis Suitable catalysts are palladium or platinum, especially on carbon as a support, alternatively such groups can be cleaved by solvolysis. Use of trifluoroacetic acid is further carried out by treating n-butyllithium in an inert solvent at room temperature.

The precise chemical structure of the protecting group does not play a decisive role, only its ability to meet the above requirements is important. The selection and identification of suitable protecting groups will not be a problem for those skilled in the art. The suitability and effectiveness of a given hydroxyl protecting group is determined by its utility in the reactions described herein. Thus, the protecting group should be one that can be easily removed by regenerating the hydroxyl group. Because of their easy cleavability, methyl and benzyl groups are preferred protecting groups.

The analgesic properties of the compounds of the invention are determined by the tests described below using irritant stimuli.

Tests using thermal stimuli

(a) Hot plate analgesic efficacy test

A modification of the procedure described by Woolfe and MacDonald [J. Pharmacoi. Exp. Ther. 80, 300-307 (1944)]. The test mice are placed on a 0.3 cm thick aluminum plate, which is heated in a controlled manner to irritate the mouse paws with heat. Below the aluminum plate is an infrared radiator with a power input of 250 W. The radiator operation is controlled by a thermal regulator coupled to thermistors on the surface of the plate so that the temperature of the plate is maintained at a constant value of 57 ° C. Each test mouse is placed in a glass cylinder (16.5 cm diameter) seated on a hot plate, and the time is counted when the animal's paw touches the plate. Experimental mice are observed at 0.5 and 2 hours after administration of the test compound to detect the first jerky movements of one or both hindpaws, or for 10 seconds in the absence of such movements. Morphine has an MPE50 value of 4 to 5.6 mg / kg (subcutaneous administration) in this assay.

(b) Mouse analgesic efficacy test, in which animals vigorously remove the tail from the site of thermal irritation

This test is a modification of the procedure described by D‘Amour and Smith [J. Pharmacoi.

Exp. Ther. 72, 74-79 (1941)], and utilizes thermal irritation of the tail of a controlled intensity mouse. Each mouse is placed in a sliding metal cylinder such that its tail protrudes at one end of the cylinder. The cylinder is arranged such that the protruding tail of the animal is in a horizontal position above the covered heat emitter. At the beginning of the test, the aluminum diaphragm is removed from the emitter and the beam of light with the slit and focus is directed to. the end of the animal's tail. At the same time the clocks start. An increase in the time required for the mouse to respond to thermal irritation by tail twitching is observed. Untreated mice usually respond to thermal irritation in 3 to 4 seconds. The endpoint of protection provided by the test substance is 10 seconds. Each mouse is tested at 0.5 to 2 hours after administration of morphine or test compound. Morphine has an MPE50 = 3, z and b, of mg / kg / kg (subcutaneous administration).

cj Tests in submerged tail mice

The method used is a modification of the procedure developed by Benbasset et al. [Sheet. int. Pharmacodyn. 122, 434 (1959)]. Male white mice (Charles River CD-I strain, weighing 19 to 21 gj) are weighed and provided with identification marks. Each substance is tested on a group of 5 animals each serving as its own control. first administered intraperitoneally or subcutaneously at a dose of 56 mg / kg given at a volume of 10 ml / kg Before and at 0.5 and 2 hours after administration of the active substance, each animal is placed in a cylinder provided with adequate ventilation and closed with a circular The cylinder is kept upright, with the protruding tail of the animal fully immersed in a water bath heated to a constant temperature of 56 ° C. The experiment always ends with an energetic twitch or pulling of the tail associated with motor response In some cases there may be tests after administration To prevent unwanted tissue damage, the experiment is terminated and the animal's tail is removed from the bath after 10 seconds. The latency of the response is recorded in seconds, rounded to 0.5 seconds. In parallel, the test is performed after application of only the vehicle and standard of known efficacy. If the efficacy of the test substance does not decrease to baseline within 2 hours after administration, the latency of the response is determined at 4 and 6 hours after administration. If, at the end of the test day, the test compound still shows efficacy, a final measurement is made 24 hours after administration.

Test using chemical stimuli

Suppression of painful convulsions (writhing) induced by phenylbenzoquinone

Groups of 5 mice (Carworth Farms CF-1) are each pre-treated by subcutaneous or oral administration of saline, morphine, codease, or test compound. Phenylbenzoquinone, which is known to induce abdominal contractions, is then administered intraperitoneally to all groups of test animals after 20 minutes (for subcutaneous administration) or 50 minutes (for oral administration). Five minutes after injection of the compound, mice are observed for 5 minutes to determine whether or not they experience painful convulsions. MPE50 values are determined for each test substance to prevent painful convulsions when administered prematurely.

Tests using pressure stimuli

Efficiency in the Haffner test

A modification of the procedure described by Haffner [Experimentelle Prufung Schmerzstillender] is used to determine the effectiveness of a test compound on an aggressive tail-induced response. Deutsch. Copper. Wschr., 55, 731-732 (1929)].

Male white rats (50-60 g) of Charles River strain (Sprague-Dawleyj CD) are used for the test. Before the test substance is administered and again at 0.5, 1, 2 and 3 hours after drug administration, the rat's tail is clamped ( John-I-Iopkins, 6.35 cm “bulldog” clampj The end point of each experiment is the explicitly offensive behavior and biting towards the pain-inducing tool, recording the latency of the response in seconds, unless the attack takes 30 seconds , the clamp is removed and the latency of the response is recorded as 30 seconds Morine is effective in this test when administered intraperitoneally at a dose of 17.8 mg / kg.

Tests using electrical stimuli

A test in which test animals bounce from the site of an electrical irritant stimulus

A modification of the procedure described by Temen [Psychopharmacologia, 12, 278-285 (1968}) is used to determine the pain threshold, using male white rats (175-200 g) of the Charles River (Sprague-Dawley) CD strain prior to administration. the test substances are immersed in the paws of all rats in a 20% glycerin solution in saline, and the animals are placed in a cage and pawed at 30-second intervals with one second electric shocks at increasing current intensity. 39, 0.52, 0.78, 1.05, 1.31, 1.58, 1.86, 2.13, 2.42, 2.72 and 3.04 mA. whether in the event of an electric shock there is also a bounce back, bj a screech and / or cj a bounce or a fast forward movement.

One series of shocks are given to each rat just prior to administration of the test substance and at 0.5, 2, 4, and 24 hours after administration of the test substance at increasing current intensity.

The results of the above tests are recorded as the maximum possible effect in% (% MPEj. The I-values of% MPE for each group are statistically compared to the% MPE for the standard and the control values observed prior to drug administration. the following formula:

Measured Time - Check Time% MPE = · -—τ-r? —R ~ rz- X 100 Interrupt Time - Check Time

When administered orally or parenterally as analgesics, the compounds of the invention are conveniently administered in the form of compositions comprising a pharmaceutical carrier selected on the basis of the chosen route of administration and taking into account standard pharmaceutical practice. For example, the compounds described herein may be administered in the form of tablets, pills, powders or granules containing, for example, starch, milk sugar, certain types of clay, as carriers, and the like. The compounds of the invention may also be administered in capsules containing the same. with equivalent carriers. The disclosed compounds may also be administered in the form of suspensions, solutions, emulsions, syrups or elixirs for oral administration, which dosage forms may contain flavoring and coloring agents. For most oral applications of the therapeutic agents of the invention, tablets or capsules containing from about 0.01 to 100 mg of active ingredient are suitable.

The most appropriate dosage for a particular patient, which will vary depending on the age, weight, response and route of administration, will be determined by the attending physician. In general, however, the initial analgesically effective dose for adult patients may range from about 0.1 to 750 mg / day, the total dose being administered in single or multiple doses. In many cases it is not necessary to exceed the daily dose of 100 mg. A suitable dosage range for oral administration is from about 1.0 to 300 mg / day, a preferred range from about 1.0 to 50 mg / day. A preferred range is 216504 for parenteral administration, from about 0.1 to 100 mg / day, a preferred range from about 0.1 to 20 mg / day.

The invention also provides pharmaceutical compositions comprising unit dosage forms suitable for use as the analgesics described above and for other applications described below. These dosage forms may be formulated as single or multiple doses, as described above, in order to achieve a daily dosage effective for each use.

The compounds of the invention may be formulated for administration as solid or liquid preparations for oral or parenteral administration. The active ingredient capsules of the present invention may be prepared by mixing 1 part by weight of the active ingredient with 9 parts of a carrier, such as starch or milk sugar, and filling the insertable gelatin capsules so that each capsule contains 100 parts of the mixture. Tablets containing the above-described compounds as active ingredients are prepared using suitable mixtures of the active ingredient and standard carriers and excipients used in the preparation of tablets, such as starch, binding agents and glidants, such that each tablet contains from 0.10 to 100 mg of active substance.

Suspensions and solutions of the compounds of the invention are often prepared just prior to use in order to avoid storage-related stability or stability problems of the active ingredient suspension or solution (e.g., precipitation of the active ingredient).

Compositions suitable for such use are generally dry, solid preparations which are then suitably formulated for injection.

The analgesic activity of several compounds according to the invention has been determined by the methods described above. These compounds correspond to the general formula

Table I shows the results of the activity tests of the compounds of the above formula wherein A is hydrogen and B a hydroxyl group, Table II shows the results of the activity tests of the compounds of the above formula wherein A and B together form an oxo group.

The following abbreviations are used in the tables for each .test:

FBCH = painful cramps caused by phenylbenzoquinone,

DO = heat irritation of tail

HD = hot plate

SO = tail clamping (Haffner),

OD = electric shock.

The ED 50 values are given in the tables (if only one number is given). The figure followed by the second number in parentheses refers to the protection in% at the given batch. Thus, a value of 31 (56) means that a dose of 56 mg / kg body weight of the test substance provides 31% protection.

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The diuretic activity of the compounds of the present invention is illustrated by the assay performed by Lipschitz et al. [J. Pharmacol., 197, 97 (1943)], using rats as test animals. The dosage range for this use corresponds to the dosage given above for the use of the compounds of the invention as analgesics.

Antidiarrheal efficacy was determined using a modification of the procedure described by Neimegeers et al. [Modern Pharmacology-Toxicology, Willem van Bever and Harbans Lal, Eds. 7, 68-73 (1976)]. Charles River CD-I rats (170-200 g) were placed in common cages 18 hours prior to the start of the test. Before castor oil administration, the animals are fasted overnight, without limiting water intake. The test substance is administered subcutaneously or orally in a constant volume of 5 ml / kg body weight, in a mixture of 5% ethanol, 5% emulsifier based on polyoxyethylated vegetable oil and 90% saline, and orally administered a challenge dose after one hour ( 1 ml] of castor oil The animals are placed in small individual cages (20.5 x 16 x 21 cm) with suspended wire plates, a cardboard strip is placed under the wire plate and 1 hour after castor oil administration, it is determined whether or not it has occurred For all tests carried out within 1 day, the control group of animals receiving only vehicle and castor oil always serves as a control, and the results are recorded as the number of animals lunged prior to diarrhea for 1 hour after castor oil administration. The dosages of the disclosed compounds as antidiarrheal agents correspond to the dosages m used in the application of these compounds as analgesics.

The transquilizing activity of the compounds of the invention is determined by orally administering test compounds to rats at doses of about 0.01 to 50 mg / kg body weight and observing the following decrease in spontaneous motor activity. The daily dosage for mammals ranges from about 0.01 to 100 mg.

Anticonvulsive activity was determined by subcutaneously administering the test compound to male mice (Charles Riverj weighing 14-23 g in a vehicle of the same type as used in the diarrheal activity test). Experiments were performed on groups of 5 mice each. mice are fasted overnight without being restricted in water intake Test compound is administered at a volume of 10 ml / kg using a subcutaneous syringe # 25. 1 hour after administration of the test substance, the animals are transcorneally shocked with 50 mA (60 Hzj) In parallel, a control experiment is conducted in which mice are given vehicle only, and electroconvulsive shock induces tonic stretcher stretcher convulsions with a latency of 1.5 to 3 seconds in all control mice. for 10 seconds after application, el. electroconvulsive shock there will be no tonic cramps of the stretcher.

Efficacy against anxiety states was determined in a manner similar to anticonvulsant, except that pentylentetrazole administered intraperitoneally at a dose of 120 mg / kg was used as a seizure agent. Administration of this agent induces clonic convulsions in more than 95% of control mice within less than 1 minute. A test substance is considered to be effective if the latency time of convulsions is at least doubled when premedicated with the substance.

Sedative / depressant efficacy was determined by administering to groups of 6 mice each subcutaneously various doses of the test compound. 30 and 60 minutes after application, mice are placed on a rotating rod for 1 minute and evaluated for their ability to remain on the rod. The inability of the treated mouse to stick to the rotating rod indicates the sedative / depressive efficacy of the test substance.

The invention is illustrated by the following non-limiting examples.

Example 1

3- (4- (1,1-Dimethylheptyl) -2-hydroxyphenyl) cyclohexanone

A mixture of 19.5 g (0.0468 mol) of 3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclohexanone, 12.3 g of sodium bicarbonate, 3.00 grams of 10% palladium on carbon and 250 ml The reaction mixture was filtered through diatomaceous earth after the addition of ethyl acetate and the filtrate was evaporated to a solid residue, which was purified by chromatography on a 280 g silica gel column using 20% silica gel. ether in cyclohexane as eluent to give a solid material which yielded 9.1 g (62%) of the title compound, predominantly in the form of hemiketal, melting at 87 ° C.

PMR (deuterochloroform, tetramethylsilane, δ values):

0.87 (multiplet, terminal methyl),

1.27 (singlet, geminal dimethyl),

1.0 - 2.2 (multiple multiplets,

3.21 (multiplet corresponding to two protons); and

6.92 (multiplet, proton of the aryl residue).

IR (KBr):

3226, 1629 and 1580 ^cm-first

IR (chloroform):

3571, 3289, 1704, 1623 and 1575 ^cm-first

Mass spectrum (m / e):

316 (M &lt; + &gt;), 298, 273 and 231.

216504 17

For C21H32O2: calculated: 79.70% C, 10.19% H, found: 79.69% C, 9.89% H.

By repeating the above procedure using the appropriate starting material, the following products are obtained:

3- (4- (1,1-Dimethylheptyl) -2-hydroxyphenyl) -3-methylcyclohexanone

This product was obtained as an oil from 80 mg (0.19 mmol) of 3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -3-methylcyclohexanone. Yield: 54 mg (86%).

IR (chloroform):

3597, 3390, 1623 and 1572 cm -1

Mass spectrum (m / e):

330 (M &lt; + &gt;), 315, 287 and 245.

trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -4-methylcyclohexanone

This product, melting after recrystallization from pentane at 62-64 ° C, was obtained from 1.05 g (2.50 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -4 -methylcyclohexanone. Yield: 825 mg (99%).

PMR (deuterochloroform, tetramethylsilane, δ j values:

0.84 (multiplet, terminal methyl in side chain),

1.28 (singlet, geminal dimethyl) a

6.75 - 7.2 (multiplet, proton of aryl residue).

IR (chloroform):

3571, 3333, 1721 (low maximum), 1626 and

1577 cm ^1st

Mass spectrum (m / e):

330 (M &lt; + &gt;), 312, 288, 273, 245, 203, and 161.

For C22H34O2: calculated: 79.97% C, 10.37% H, found: 80.33% C, 10.30% H.

3- [4- (1,1-Dimethylheptyl} -2-hydroxyphenyl] cyclopentanone

This product, melting after crystallization from pentane at 61-62 ° C, was obtained from 1.50 g (3.83 mmol) of 3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclopentanone. Yield: 0.54 g (47%).

PMR (deuterochloroform, tetramethylsilane, δ values):

0.88 (multiplet, terminal methyl in side chain),

1.29 (singlet, geminal dimethyl),

2.0 - 3.0 (multiplet, methylenes on C 2, C 4 and C 5),

3.70 (multiplet, meth group of the benzyl residue),

5.90 (singlet, phenol),

6.82 (broad singlet superimposed at 6.92, aryl residue proton),

6.92 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.17 (doublet, J = 8 Hz, proton of the aryl residue).

IR (KBr):

3279, 1739, 1621 and 1577 ^cm-first

Mass spectrum (m / e):

302 (M &lt; + &gt;), 283, 217, 189, 175 and 161.

For C20H30O2: calculated: 79.42% C, 10.00% H, found: 79.65% C, 10.03% H.

3- [441,1-Dimethylheptyl) -2-hydroxyphenyl] cycloheptanone

This product, melting after crystallization from pentane at 78-79 ° C, was obtained from 1.60 g (3.80 mmol) of 3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cycloheptanone. Yield 795 mg (63%).

PMR (deuterochloroform, tetramethylsilane, δ values):

0.84 (multiplet, terminal methyl),

1.25 (singlet, geminal dimethyl),

6.80 (broad singlet overlapping at 6.88, aryl residue proton),

6.88 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue),

7.10 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3571, 3289, 1701, 1621, 1605 and 1577 cm ^-1 .

Mass spectrum (m / ej):

330 (M + 1 and 245.

H, 10.37; H, 10.37. Found: C, 79.60; H, 10.33.

3- [2-Hydroxy-4- (2-5-phenylpentyloxy) phenyl] cyclohexanone

This product, obtained as an oil, was obtained in quantitative yield from 1.0 g (2.26 mmol) of 3- [2-benzyloxy-4- (2- (5-phenylpentyloxy) phenyl] cyclohexanone.

PMR (deuterochloroform, tetramethylsilane, δ values):

1.28 (doublet, J = 6 Hz, methyl),

2.7 (multiplet, two methylenes),

3.12 (multiplet, methine group of the benzyl residue),

4.30 (multiplet, inethin group in the side chain),

6.32 (doublet, J = 2 Hz, proton of the aryl residue),

6.32 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue),

6.80 (doublet, J = 8 Hz, proton of the aryl residue) and

7.18 (singlet, phenyl proton).

IR (chloroform):

3571, 3333, 1709, 1623 and 1587 cm ^-1 .

Mass spectrum (m / e):

352 (M &lt; + &gt;), 206, 188 and 91.

3- (2,4-Dihydroxyphenyl) cyclohexanone

This product, melting after crystallization from isopropyl ether at 158 DEG C., is obtained from 8.5 g (94%) of 16.9 g (43.7 mmol) of 3- (2,4-dibenzyloxyphenyl) cyclohexanone.

PMR (perdeuterodimethylsulfoxide, tetramethylsilane, δ values):

1.3 - 3.5 (multiple multiplets)

6.1 - 6.8 (several multiplets, proton aryl residue and hydroxyl);

6.93 (doublet, 1 = 8 Hz, proton of the aryl residue).

IR (KBr):

3195, 1631 and 1603 cm -1.

Mass spectrum (m / e):

206 (M &lt; + &gt;), 188, 163, 149 and 136.

H, 6.84; Found: 69.94 ° C, 6.78 ° H.

3- (4- (1,1-Dimethyloctyl) -2-hydroxyphenyl] cyclohexanone

This product, melting after crystallization from pentane at 78 ^DEG- 80 ^DEG C., is obtained from 2.00 g (4.76 mmol) of 3- [2-benzyloxy-4- (1,1-dimethyloctyl) phenyl] cyclohexanone (yield: 0). , 75 grams (48%).

PMR (deuterochloroform, tetramethylsilane, δ values):

0.83 (multiplet, terminal methyl iv side chain),

1.22 (singlet, geminal dimethyl) and

6.85 (multiplet, proton of aryl residue). IR (chloroform):

3571, 3333, 1709 (weak maximum), 1626 and 1577 cm ^-1 .

Mass spectrum (m / e):

330 (M &lt; + &gt;), 314, 312, 287 and 231.

H, 10.37; Found: C, 79.97; H, 9.99.

3- (4-tert-Butyl-2-hydroxyphenyl) cyclohexanone

This product, melting after crystallization from isopropyl ether at 177-178 ° C, is obtained from 4.2 g (10.0 g, 0.0298 mol) of 3- (2-benzyloxy-4-tert-butylphenyl) cyclohexanone (m.p. 58 °

PMR (perdeuterodimethylsulfoxide, tetramethylsilane, S j values:

1.25 (singlet, t-butyl),

6.7 - 6.9 (multiplet, two protons of the aryl residue) and

7.02 (doublet, J = 8 Hz, proton of the aryl residue).

IR (KBr):

3279, 1639 and 1592 cm ^-1 .

Mass spectrum (m / e):

246 (M &lt; + &gt;), 231, 228, 215, 213, 203, 189, 176 and 161.

3- (4- (1,1-Dimethylpropyl) -2-hydroxyphenyl] cyclohexanone

This product, melting after crystallization from isopropyl ether at 165-166 ° C, is obtained from

7.50 g (0.0214 mol) of 3- [2-benzyloxy-4- (1,1-dimethylpropyl) phenyl] cyclohexanone. Yield: 2.52 g (45%).

PMR (perdeuterodimethylsulfoxide, tetramethylsilane, δ j values:

0.63 (triplet, J = 7 Hz, terminal methyl),

1.11 (singlet, geminal dimethyl),

6.8 (multiplet, aryl residue proton and hydroxyl),

7.10 (doublet, J = 8 Hz, arly residue proton).

IR (chloroform):

3636, 3401, 1724 (low maximum), 1634 and 1587 cm ^-1 .

Mass spectrum (m / e):

260 (M &lt; + &gt;), 242, 231, 217, 213 and 161.

For C17H21O2: calculated: 78.42% C, 9.29% H, found: 78.17% C, 9.22% H.

3- (4- (1,1-Dimethylbutyl) -2-hydroxyphenyl) cyclohexanone

This product, melting after crystallization from isopropyl ether at 101-102 ° C, was prepared from 7.00 g (0.0192 mol) of 3- [2-benzyloxy-4- (1,1-dimethylbutyl) phenyl] cyclohexanone. 0.6 g (11%).

PMR (deuterochloroform, tetramethylsilane, δ values):

0.82 (multiplet, terminal methyl),

1.25 (singlet, geminal dimethyl) and

6.80 (multiplet, proton aryl residue).

IR (chloroform):

3636, 3401, 1724 (low maximum), 1634 and 1585 cm ^-1 .

Mass spectrum (m / e):

274 (M &lt; + &gt;), 256, 231 and 213.

H, 9.55; Found: C, 78.78; H, 9.21.

trans-3- [4- (1,1-Diinomethylheptyl) -2-hydroxyphenyl] -4-propylcyclohexanone

This product, obtained in oily form, is prepared from 1.65 g (3.69 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -4- (2-propenyl) cyclohexanone. Yield 1.0 g (76%).

IR (chloroform):

3610, 3390, 1718 (thin band), 1629 and 1577 cm ^-1 .

Mass spectrum (m / e):

358 (M &lt; + &gt;), 340, 288, 273, 255, 203 and 161.

PMR (deuterochloroform, tetramethylsilane, values of 5):

0.9 (multiplet, terminal methyls),

1.22 (singlet, geminal dimethyls),

6.70 (double doublet, J = 8 Hz and J = 2 Hz, proton of aryl residue),

6.75 (doublet, J = 2 Hz, hence an aryl residue) and

6.87 (doublet, J = 8 Hz, proton of the aryl residue).

3- (4- (1,1-Dimethylpentyl) -2-hydroxyphenyl) cyclohexanone

This product, melting after crystallization from pentane at 124.5 to 125.5 ° C, was prepared from 5.5 g (0.0146 mol) of 3- [2-benzyloxy-4- (1,1-dimethylpentyl) phenyl] cyclohexanone. Yield 4.0 g (95%).

IR (chloroform):

3623, 3378, 1718 (weak band), 1634 and 1587 cm ^-1 .

Mass spectrum (m / e):

288 (M &lt; + &gt;), 245 and 231.

P

For C19H28O2: calculated: 79.12% C, 9.79% H, found: 79.32% C, 9.53% H.

3- (4- (1,1-Dimethylhexyl) -2-hydroxyphenyl) cyclohexanone

This product, melting at 82-83 ° C, was obtained in quantitative yield from 2.0 g (5.1 mmol) of 3- [2-benzyloxy-4- (1,1-dimethylhexyl) phenyl] cyclohexanone.

IR (chloroform):

3636, 1634, 1616 and 1585 cm ^-1 .

Mass spectrum (m / e):

302 (M &lt; + &gt;), 284, 259 and 231.

PMR (deuterochloroform, tetramethylsilane, values of 5):

0.82 (singlet, terminal methyl)

1.23 (singlet, geminal dimethyl),

3.10 (multiplet)

3.55 (multiplet)

6.83 (multiplet, proton of aryl residue).

For C20H30O2: calculated: 79.42% C, 10.00% H, found: 79.16% C, 9.75% H.

3- (4- (1,1-Dimethylnonyl) -2-hydroxyphenyl] cyclohexanone

This product, melting at 72-73 ° C, was prepared from 5.0 g (11.5 mmol) of 3- [2-benzyloxy-4- (1,1-dimethylnonyl) phenyl] cyclohexanone. Yield 2.4 g (61%).

IR (chloroform):

3650, 3413, 1721 (thin band), 1639 and 1595 cm ^-1 .

High resolution mass spectrum (m / e):

344.2691 (M ⁺ ) for C 23 H 36 O 2, 326.2570 and

301.2168.

PMR (deuterochloroform, tetramethylsilane, values of 5):

0.87 (multiplet, terminal methyl),

1.28 (singlet, geminal dimethyl),

3.10 (multiplet) a

6.85 (multiplet, proton of aryl residue).

3- (4- (1,1-Dimethyldecyl) -2-hydroxyphenyl] cyclohexanone

This product, m.p. 78 DEG-79 DEG C., was prepared from 2.0 g (4.46 mmol) of 3- [2-benzyloxy-3- (1,1-dimethyldecyl) phenyl] cyclohexanone, yield 880 mg (m.p. 55%).

IR (chloroform):

3623, 1629, 1616 and 1587 cm -1.

High resolution mass spectrum (m / e J):

358.2836 (M ⁺ j for C 24 H 38 O 2).

PMR (deuterochloroform, tetramethylsilane, values of 5):

0.88 (multiplet, terminal methyl),

1.27 (singlet, geminal dimethyl),

3.15 (multiplet) and

6.85 (multiplet, proton of aryl residue).

3- [4- (1,1-Dimethyl -undecyl) -2-hydroxy-phenyl] -cyclohexanone

This product, melting at 72-73 ^° C, was prepared from 4.00 g (8.66 mmol) of 3- [2-benzyl-oxy-4- (1,1-dimethylundecyl) -phenyl] -cyclohexanone. Yield 1.49 g (46%).

IR (KBr):

3268, 1629 and 1580 cm ^-1 .

Mass spectrum (m / c):

372 (M &lt; + &gt;), 354, 329 and 231.

PMR (deuterochloroform, tetramethylsilane, values <5):

0.87 (multlplet, terminal methyl),

1.24 (singlet, geminal dimethyl),

3.16 (multlplet)

3.42 (multiplet) and

6.88 (multiplet, proton of aryl residue).

H, 10.82; H, 10.82. Found: C, 80.70; H, 10.84.

3- [4- (1,1-Dimethylhephyl) -2-hydroxyphenyl] cyclooctanone

This product, m.p. 118 DEG C., was prepared from 3.92 g (1.95 g, 81%) of 3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclooctane. %).

IR (chloroform):

3623, 3356, 1709, 1629 and 1587 ^cm-first

Mass spectrum (m / e):

344 (M &lt; + &gt;), 329, 326, 283, 273, 259, and 241.

PMR (deuterochloroform, tetramethylsilane, δ values):

0.82 (multiplet, terminal methyl),

1.27 (singlet, geminal dimethyl),

3.55 (broad multiplet, meth group of the benzyl residue),

6.76 (doublet, J = 2 Hz, aryl residue proton),

6.78 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.02 (doublet, J = 8 Hz, proton of the aryl residue).

For C23H36O2: calculated: 80.18% C, 10.53% H, found: 79.92% C, 10.37% H.

3- (4- (1,1-Dimethylheptyl) -2-hydroxyphenyl) -4-methyl-2-cyclohexen-1-one

This product, melting after crystallization from a mixture of diisopropyl ether and petroleum ether at 111 ° C, was prepared from 2.10 g (5.02 mmol) of 3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -4- methyl 2-cyclohexen-1-one. Yield 1.15 g (70%).

IC (chloroform):

3534, 3279, 1667, 1623 and 1567 cm ^-1 .

Mass spectrum (m / e):

328 (M &lt; + &gt;), 313 and 243.

PMR (deuterochloroform, tetramethylsilane, δ values):

0.83 (multiplet, terminal methyl),

1.10 (doublet, J = 7 Hz, methyl),

1.25 (singlet, geminal dimethyl),

2.6 (multlplet, methylene),

3.2 (multiplet, methine),

6.32 (wide singlet, vinyl group proton),

6.63 (singlet, hydroxyl),

6.9 (multiplet, proton aryl residue), 7.08 (doublet, J = 8 Hz, proton aryl residue).

H, 9.83; Found: C, 80.35; H, 9.67.

Example 2 cis-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] cyclohexanol

A mixture of 22.0 g (0.0539 mol) of cis-3 - [- benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclohexanol, 12.0 g of sodium bicarbonate, and 2.0 g of 10% polysaccharide with 2 The mixture was stirred under a hydrogen pressure of 1 bar for 1 hour. After addition of ethyl acetate, the reaction mixture was filtered through diatomaceous earth and the filtrate was evaporated. The solid residue was recrystallized from hexane to give 13.2 g (77%) of the title compound, melting at 109-110 ° C.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.81 [multiplet, terminal methyl],

1.25 (singlet, geminal dimethyl),

2.80 (broad multiplet, meth group of the benzyl residue,

3.80 (broad multiplet, methine grouping of carbinol residue),

5.4 (broad signal, hydroxyl),

6.63 (broad singlet, proton of the aryl residue),

6.77 (double doublet, J = 8 Hz and J = 2 Hz),

6.87 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3610, 3356, 1626 and 1582 ^cm-first

Mass spectrum (m / e):

318 (M &lt; + &gt;), 300, 233 and 215.

For C21H34O2: calculated: 79.19% C, 10.76% H, found: 78.96% C, 10.59% H.

Using the above procedure, the following products are obtained using the appropriate starting materials:

trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane at 124-125 ° C, was prepared from 4.50 g (0.011 mol) of trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cycloliexanol. Yield: 2.47 g (71%).

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.81 (multiplet, terminal methyl),

1.25 (singlet, geminal dimethyl),

3.25 (multiplet, meth group of the benzyl residue),

4.22 (multiplet, methine grouping of carbinol residue),

6.81 (doublet, J = 2 Hz, aryl residue proton),

6.81 (double doublet, J = 8 Hz and J = 2 Hz),

7.08 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3610, 3390, 1626 and 1575 cm ^-1 .

Mass spectrum (m / e):

318 (M &lt; + &gt;), 300, 233 and 215.

H, 10.76; Found: C, 78.82; H, 10.43.

Z-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -3-methylcyclohexanol

This product, melting after recrystallization from petroleum ether at 90-91 ° C, was prepared in quantitative yield from 180 mg (0.246 mmol) of Z-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -3- methylcyclohexanol.

PMR (deuterochloroform, tetramethylsilane, values of 5):

0.85 (multiplet, terminal methyl in side chain),

1.25 (singlet, geminal dimethyl),

1.33 (singlet, Cs-methyl),

3.65 (multiplet, methine grouping of carbinol residue),

5.48 (broad singlet, hydroxyl),

6.63 (doublet, J = 2 Hz, proton of the aryl residue),

6.82 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.19 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3597, 3333, 1605 and 1570 ^cm-first

Mass spectrum (m / e):

332 (M &lt; + &gt;), 314, 299, 286, 271, 247, and 229.

H, 10.92; Found: C, 79.24; H, 10.64;

trans, trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -4-methylcyclohexanol

This product, melting after crystallization from pentane at 134-135 ° C, was prepared in quantitative yield from 190 mg (0.450 mmol) of tris, trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -4-methylcyclohexanol.

PMR (deuterochloroform, tetramethylsilane, δ '):

0.7 - 0.9 (multiplet, methyl to C4 and terminal methyl in the side chain),

1.24 (singlet, geminal dimethyl),

3.00 (multiplet, meth group of the benzyl residue),

4.22 (multiplet, methine grouping of carbinol residue),

6.78 (doublet, J = 2 Hz, proton of the aryl residue),

6.88 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.02 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3571, 3333, 1626 and 1575 cm ^-1 .

Mass spectrum (m / e):

332 (M &lt; + &gt;), 317, 314, 247, 233 and 229.

For C22H36O2: calculated: 79.46% C, 10.92% H, found: 79.13% C, 10.68% H.

cis, trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -4-methylcyclohexanol

This product, melting after crystallization from pentane at 150-151 [deg.] C., was prepared in quantitative yield from 1.15 g (2.72 mmol) of cis, trans-3- [benzyloxy-4- (1,1-dimethylheptyl). Phenyl] -4-methylcyclohexanol.

PMR (deuterochloroform, tetramethylsilane, ά values):

0.72 (doublet, J = 6 Hz, methyl on C4),

0.86 (multiplet, terminal methyl in side chain),

1.24 (singlet, geminal dimethyl),

2.62 (multiplet, meth group of the benzyl residue),

3.77 (multiplet, methine grouping of carbinol residue),

6.70 (doublet, J = 2 Hz, proton of aryl residue),

6.83 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.04 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3571, 3333, 1621, 1605 and 1580 cm ^-1 .

Mass spectrum (m / e):

332 (M &lt; + &gt;), 314, 272, 247, 233 and 229.

For C22H36O2: calculated: 79.46% C, 10.92% H, found: 79.15% C, 10.72% H.

cis-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] cyclopentanol and the corresponding trans-isomer

These products, obtained in oily form, are prepared from 1.10 g (2.79 mmol) of a mixture of cis- and trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclopentanol. The yield of the cis isomer is 464 mg (55%), the yield of the trans isomer is 228 mg (27%). cis-Isomer:

PMR (deuterochloroform, tetramethylsilane, values <$):

0.83 (multiplet, terminal methyl in side chain),

1.24 (singlet, geminal dimethyl),

3.2 (multiplet, meth group of benzyl residue),

4.52 (multiplet, methine grouping of carhinol residue),

6.75 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue),

6.81 (broad singlet, superimposed at 6.75, aryl residue proton),

6.97 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3571, 3300, 1623 and 1567 ^cm-first

Mass spectrum (m / e):

304 (M ^& lt ^{; +} & gt ^; ), 286, 219, 201 and 159.

trans-isomer:

PMR (deuterochloroform, tetramethylsilane, values <S):

0.83 (multiplet, terminal methyl in side chain),

1.27 (singlet, geminal dimethyl),

3.60 (multiplet, methine group of the benzyl residue),

4.55 (multiplet, methine grouping of carhinol residue),

6.78 (broad singlet, superimposed at 6.88, aryl residue proton),

6.88 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.10 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3571, 3333, 1621 and 1575 ^cm-first

Mass spectrum (m / e):

304 (M ^& lt ^{; +} & gt ^; ), 286, 219 and 201.

trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] cycloheptanol

This product, melting at 55-57 ° C, was prepared in quantitative yield from 695 mg (1.64 mmol) of trans-3- (2-benzyioxy-4- (1,1-dimethylheptyl) phenyl) cycloheptanol.

PMR (deuterochloroform, tetramethylsilane, δ '):

0.88 (multiplet, terminal methyl),

1.22 (singlet, geminal dimethyl),

3.20 (multiplet, methine grouping of the benzyl residue),

4.22 (multiplet, methine grouping of carhinol residue),

6.85 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue),

6.90 (broad singlet, superimposed at 6.85, proton of aryl residue);

7.13 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3333, 1621 and 1570 ^cm-first

Mass spectrum (m / e):

332 (M ^& lt ^{; +} & gt ^; ), 314, 247 and 229.

H, 10.92; Found: C, 79.68; H, 10.62.

cis-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] cycloheptanol

This product, melting after crystallization from pentane at 103-104 ° C, was prepared in quantitative yield from 380 mg (0.900 mmol) of cis-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cycloheptanol,

PMR (deuterochloroform, tetramethylsilane, values of 5):

0.82 (multiplet, terminal methyl),

1.20 (singlet, geminal dimethyl),

3.0 (multiplet, meth group of the benzyl residue),

4.0 (multiplet, methine grouping of carhinol residue),

6.72 (broad singlet, superimposed at 6.81, proton of the aryl residue),

6.81 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.08 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3571, 3311, 1621, 1605 and 1580 ^cm-first

Mass spectrum (m / e):

332 (M ^& lt ^{; +} & gt ^; ), 314, 247 and 229.

H, 10.92; Found: C, 79.39; H, 10.72.

cis-3- [2-Hydroxy-4- (2- (5-phenylpentyloxy)) phenyl] cyclohexanol

This product, melting after recrystallization from pentane at 80-84 ° C, was prepared in quantitative yield from 1.45 g (3.27 mmol) of cis-3- [2-benzyloxy-4- (2- / 5-phenylpentyloxy). (i) phenyl] cyclohexanol.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

1.25 (doublet, J = 6 Hz, methyl)

3.75 (multiplet, methine grouping of carbinol residue),

4.20 (multiplet, methine grouping in side chain),

6.23 (broad singlet, proton of the aryl residue),

6.40 (double doublet, J = 8 Hz and J = 2 Hz,

6.98 (doublet, J = 8 Hz, proton of the aryl residue) and

7.13 (singlet, proton of phenyl residue).

IR (chloroform):

3597, 3333, 1623 and 1597 cm ^-1 .

Mass spectrum (ni / e):

354 (M &lt; + &gt;), 336, 208, 190 and 91.

For C23H30O3: calculated: 77.93% C, 8.53% H, found: 77.95% C, 8.31 ° / o H.

trans-3- (2-Hydroxy-4- (2- (5-phenylpentyloxy)) phenyl] cyclohexanol

This product, melting after crystallization from pentane at 65-70 ° C, was prepared from 0.355 g (0.754 mmol) of trans -3- [2-benzyloxy-4- (2- (5-phenylpentyloxy) phenyl] cyclohexanol). 241 mg (90%).

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

1.25 (doublet, J = 6 Hz, side chain methyl group),

4.13 (multiplet, methine groupings in carbinol residue and side chain),

6.26 (doublet, J = 2 Hz, proton of the aryl residue),

6.26 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue),

6.26 (double doublet,) = 8 Hz and J = 2 Hz, proton of the aryl residue),

6.82 (doublet, l = 8 Hz, proton of the aryl residue) and

7.05 (singlet, proton of the phenyl residue).

IR (chloroform):

3597, 3378, 1629 and 1587 cm ^-1 .

Mass spectrum (m / e):

354 (M &lt; + &gt;), 336, 208, 190 and 91.

H, 8.53; Found: C, 77.53; H, 8.40.

cis-3- [4- (1,1-Dimethyloctyl) -2-hydroxyphenyl) cyclohexanol

This product, melting after recrystallization from hexane at 100-101 ° C, was prepared from 1.36 g (3.22 mmol) of cis-3- (2-benzyloxy-4- (1,1-dimethyloctyl) phenyl] cyclohexanol. Yield: 0.725 g (68%).

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.82 (multiplet, terminal methyl in side chain),

1.22 (singlet, geminal dimethyl),

2.90 [multiplet, meth group of benzyl residue),

3.12 (broad singlet, hydroxyl),

3.70 (multiplet, methine grouping of carbinol residue),

6.62 (doublet, J = 2 Hz, proton of aryl residue j,

6.75 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue) and

7.00 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3571, 3333, 1626 and 1582 cm ^-1 .

Mass spectrum (m / ej):

332 (M ^{+ 1} , 314, 233 and 215).

For C22H36O2: calculated: 79.46% C, 10.92% H, found: 79.85% C, 11.03% H.

trans-3- [4- (1,1-Dimethyloctyl) -2-hydroxyphenyl] cyclohexanol

This product was obtained as an oil from 246 mg (0.582 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethyloctyl) phenyl] cyclohexanol. Yield 0.195 g (100%). After recrystallization from petroleum ether, the product melts at 94-95 ° C.

PMR (deuterochloroform, tetramethylsilane)

0.82 (multiplet, terminal methyl in side chain),

1.24 (singlet, geminal dimethyl),

3.28 (multiplet, meth group of the benzyl residue),

4.20 (multiplet, methine grouping of carbinol residue and hydroxyl),

6.83 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue,

6.83 (doublet, 1 = 2 Hz, proton of the aryl residue] a

7.10 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3650, 3436, 1639 and 1582 cm ^-1 .

Mass spectrum (m / e):

332 (M ^& lt ^{; +} & gt ^; ), 314, 233 and 215.

For C22H36O2: calculated: 79.46% C, 10.92% H, found: 79.34% C, 10.55% H.

cis-3- (4-tert-butyl-2-hydroxyphenyl) cyclohexanol

This product, melting after crystallization from isopropyl ether at 177-178 ° C, was prepared from 7.1 g (0.021 mol) of cis-3- (2-benzyloxy-4-tert-butylphenyl) cyclohexanol. The yield is

3.99 g (77%).

PMR (deuterochloroform, tetramethylsilane, S-values):

1.23 (singlet, t-butyl),

2.88 (multiplet, meth group of the benzyl residue),

3.55 (multiplet, methine grouping of carbinol residue),

6.75 (multiplet, two protons of the aryl moiety) and

6.92 (doublet, J = 8 Hz, proton of the aryl residue).

IR (KBr):

3484, 3268, 1634 and 1592 cm -1.

Mass spectrum (m / e):

248 (M &lt; + &gt;), 233, 230, 215, 187, 176, 173, 161.

For C16H25O2: calculated: 77.37% C, 9.74% H, found: 77.00% C, 9.54% H.

trans-3- (4-tert-Butyl-2-hydroxy-phenyl) -cyclohexanol

This product, melting after crystallization from isopropyl ether at 136-137 ° C, was prepared from 1.25 g (2.96 mmol) of trans-3- (2-benzyloxy-4-tert-butylphenyl) cyclohexanol. Yield: 0.725 g (99%).

PMR (deuterochloroform, tetramethylsilane, values of 5):

1.27 (singlet, t-butyl),

3.35 (multiplet, meth group of the benzyl residue),

4.32 (multiplet, methine grouping of carbinol residue),

6.95 (doublet, J = 2 Hz, proton of the aryl residue),

6.96 (double doublet, J-8HzaJ = 2 Hz, proton aryl residue) a

7.15 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3623, 3401, 1626 and 1575 cm ^-1 .

Mass spectrum (m / e):

248 (M &lt; + &gt;), 233, 230, 215, 187 and 173.

For C16H24O2: calculated: 77.37% C, 9.74% H, found: 77.34% C, 3.49% H.

cis-3- [4- (1,1-Dimethylpropyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from isopropyl ether at 166-167 ^° C, was prepared from 6.1 g (0.0173 mol) of cis -3- [2-benzyloxy-4- (1,1-dimethylpropyl) phenyl] cyclohexanol. Yield 1.45 g (32%).

PMR (deuterochloroform, tetramethylsilane, values of i):

0.65 (triplet, J = 7 Hz, terminal methyl),

1.20 (singlet, geminal dimethyl),

2.91 (multiplet, methine group of the benzyl residue),

3.62 (multiplet, methine grouping of carbinol residue),

6.75 (multiplet, two protons of the aryl residue),

7.02 (doublet, J = 8 Hz, proton of aryl residue);

7.55 (singlet, hydroxyl).

IR (KBr):

3509, 3279, 1629 and 1592 ^cm-first

Mass spectrum (m / e):

262 (M ^& lt ^{; +} & gt ^; ), 247, 244, 233 and 215.

trans-3- [4- (1,1-Dimethylpropyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from isopropyl ether at 124-125 ° C, was prepared from 1.00 g (2.84 mmol) of trans -3- [2-benzyloxy-4- (1,1-dimethylpropyl) phenyl] cyclohexanol. Yield 0.50 g (68%).

PMR (deuterochloroform, tetramethylsilane, values <S):

0.67 (triplet, J = 7 Hz, terminal methyl),

1.23 (geminal dimethyl),

3.30 (multiplet, meth group of the benzyl residue),

4.05 (multiplet, methine grouping of carbinol residue),

6.76 (multiplet, two protons of the aryl residue) and

6.93 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3636, 3413, 1639 and 1585 ^cm-first

Mass spectrum (m / e):

262 (M &lt; + &gt;), 247, 244, 233 and 215.

Analysis: Found: C, 77.51; H, 9.87.

calculated: 77.82% C, 9.99% H, cis-3- [4- (1,1-Dimethylbutyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane at 138-139 ° C, was prepared from 3.39 g (9.26 mmol) of cis -3- [2-benzyloxy-4- (1,1-dimethylbutyl) phenyl] cyclohexanol. Yield: 1.9 g (74%).

PMR (deuterochloroform, tetramethylsilane, values <$):

0.82 (multiplet, terminal methyl),

1.25 (singlet, geminal dtmethyl),

2.90 (multiplet, meth group of the benzyl residue),

3.78 (multiplet, methine grouping of carbinol residue),

6.8 (multiplet, proton of aryl residue);

7.11 (doublet, J = 8 Hz, proton of the aryl residue).

IR (KBr):

3509, 3279, 1629 and 1592 cm -1

Mass spectrum (m / e):

276 (M &lt; + &gt;), 261, 258, 233 and 215.

trans-3- [4- (1,1-Dimethylbutyl) -2-hydroxyphenyl] cyclohexanol

This product was prepared as an oil from 0.700 g (1.91 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylbutyl) phenyl] cyclohexanol. Yield: 0.45 g (87%).

PMR (deuterochloroform, tetramethylsilane, values of 5):

0.80 (multiplet, terminal methyl),

1.22 (singlet, geminal dimethyl),

3.25 (multiplet, meth group of the benzyl residue),

4.22 (multiplet, methine grouping of carbinol residue),

6.81 (doublet, J = 2 Hz, aryl residue proton),

6.81 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.06 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3636, 3390, 1629 and 1575 cm ^-1 .

Mass spectrum (m / e):

276 (M &lt; + &gt;), 261, 258, 233 and 215.

trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -cis-4-propylcyclohexanol

This product, melting at 92-94 ° C, was prepared from 1.0 g (2.23 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -cis-4- ( 2-propenyl) cyclohexanol. The yield was 626 mg (78%).

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.85 (multiplet, terminal methyls),

1.25 (singlet, geminal dimethyl),

3.05 (multiplet, meth group of the benzyl residue),

4.22 (multiplet, methine grouping of carbinol residue),

6.55 to 6.9 (multiplet, proton of aryl residue),

7.01 (doublet, J = 8 Hz, proton of the aryl residue).

IR (chloroform):

3623, 3390, 1629 and 1578 cm ^-1 .

For C24H40O2: calculated: 79.94% C, 11.18% H, found: 80.10% C, 10.89% H.

cis-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -trans-4-propylcyclohexanol

This product, melting after crystallization from pentane at 126 ° C, was prepared from 930 mg (2.07 mmol) of cis -3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -trans-4- ( 2-propenyl) cyclohexanol. Yield: 550 mg (74%).

IR (chloroform):

3597, 3390, 1629 and 1575 cm ^-1 .

Mass spectrum (m / e):

360 (M ^& lt ^{; +} & gt ^; ), 345, 342, 275 and 257.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.82 (multiplet, terminal methyls),

1.27 (singlet, geminal dimethyl),

2.65 (multiplet, meth group of the benzyl residue),

3.75 (multiplet, methine grouping of carbinol residue),

6.75 (multiplet, aryl residue proton) and

7.07 (doublet, J = 8 Hz, proton of the aryl residue).

H, 11.18; Found: C, 79.85; H, 10.95;

trans-4-Butyl-cis-3- [4- (1,1-dimethylheptyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane at 131 ° C, was prepared from 500 mg (1.08 mmol) of cis -3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -trans-4- ( 2-butenyl) cyclohexanol. Yield: 322 mg (80%).

IR (chloroform):

3636, 3356, 1629 and 1587 cm ^-1 .

Mass spectrum (m / e):

374 (M ⁺ ), 356, 302,289,272,271,257,

247, 233, 217, 187, and 161.

PMR (deuterochloroform, tetramethylsilane, values of i):

0.8 (multiplet, terminal methyls),

1.28 (singlet, geminal dimethyl),

2.67 (multiplet, meth group of the benzyl residue),

3.70 (multiplet, methine grouping of carbinol residue),

6.69 (doublet, J = 2 Hz, proton of the aryl residue),

6.82 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.07 (doublet, J = 8 Hz, proton of the aryl residue).

trans-4-Pentyl-cis-3- [4- (1,1-dimethylheptyl) -2-hydroxyphenyl] cyclohexanol

This product, melting at 135-136 ° C, was prepared from 363 mg (0.762 mmol) of cis-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -trans-4- (2-pentenyl) Yield: 225 mg (76%).

PMR (deuterochloroform, tetramethylsilane, values of i):

0.8 (multiplet, terminal methyls),

1.23 (singlet, geminal dimethyl),

2.65 (multiplet, methine group of benzyl residue),

3.75 (multiplet, methine grouping of carbinol residue),

4.88 (singlet, hydroxyl),

6.78 (multiplet, proton of aryl residue) and

7.02 (doublet, J = 8 Hz, proton of aryl residue j.

cis-3- [4- (1,1-Dimethylpentyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane and isopropyl ether at 112-113 ° C, was prepared from 5.5 g (0.0144 mol) of cis -3- [2-benzyloxy-4- (1,1-dimethylpentyl) phenyl]. The yield was 2.5 g (60%).

IR (chloroform):

3636, 3390, 1631 and 1592 cm ^-1 .

Mass spectrum (m / e):

290 (M &lt; + &gt;), 272, 233 and 215.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.80 (multiplet, terminal methyl),

1.20 (singlet, geminal dimethyl),

2.90 (multiplet, methylene group of the benzyl residue),

3.61 (multiplet, methine carbinol moiety) and

6.4 - 7.1 (multiplet, proton of the aryl residue).

For C19H50O2: calculated: 78.57% C, 10.41% H, found: 78.76% C, 10.11% H.

trans-3- (4- (1,1-Dimethylphenyl) -2-hydroxyphenyl) cyclohexanol

This product, melting after crystallization from pentane at 114-115 ° C, was prepared from 640 mg (1.68 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylpentyl) phenyl] cyclohexanol. 385 mg (78%).

IR (chloroform):

3636, 3390, 1631 and 1577 cm ^-1 .

Mass spectrum (m / e):

290 (M &lt; + &gt;), 272, 233 and 215.

PMR (deuterochloroform, tetramethylsilane, values of i):

0.80 (multiplet, terminal methyl),

1.27 (singlet, geminal dimethyl),

3.30 (multiplet, meth group of the benzyl residue),

4.28 (multiplet, methine grouping of carbinol residue),

4.72 (broad singlet, hydroxyl),

6.81 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue),

6.81 (doublet, J = 2 Hz, proton of the aryl residue);

7.03 (doublet, J = 8 Hz, proton of the aryl residue).

H, 10.41; Found: C, 78.38; H, 10.10.

cis-3- [4- (1,1-Dimethylhexyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane at 98-100 ° C, was prepared from 3.00 grams (7.61 mmol) of cis -3- [2-benzyloxy-4- (1,1-dimethylhexyl) phenyl] cyclohexanol. Yield 2.3 g (99%).

IR (chloroform):

3636, 3367, 1626 and 1587 cm ^-1 .

Mass spectrum (m / e):

304 (M &lt; + &gt;), 286, 233 and 215.

PMR (deuterochloroform, tetramethylsilane, values <$):

0.82 (multiplet, terminal methyl),

1.20 (singlet, geminal dimethyl),

2.92 (multiplet, meth group of the benzyl residue),

3.76 (multiplet, methine grouping of carbinol residue) and

6.65 to 7.4 (multiplet, proton of the aryl residue).

H, 10.59; Found: C, 78.57; H, 10.46.

trans-3- [4- (1,1-Dimethylhexyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane at 113-114 ° C, was prepared from 660 mg (1.68 mmol) of trans-3- [2-benzyl-oxy-4- (1,1-dimethylhexyl) phenyl] cyclohexanol. Yield: 440 mg (86%).

IR (chloroform):

3636, 3390, 1631, 1616 and 1580 ^cm-first

Mass spectrum (m / e):

304 (M &lt; + &gt;), 286, 233 and 215.

High resolution mass spectrum:

304.2419 (C20H32O2).

cis-3- [4- (1,1-Dimethylnonyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane at 82-83 ° C, was prepared from 5.0 g (1.15 mmol) of cis -3- [2-benzyloxy-4- (1,1-dimethylnonyl) phenyl] cyclohexanol. Yield 4.0 g (100%).

IR (chloroform):

3350, 3390, 1637 and 1597 cm ^-1 .

Mass spectrum (m / e):

346 (M ^& lt ^{; +} & gt ^; ), 328, 233 and 215.

H, 11.05; H, 11.05. Found: C, 79.71; H, 11.14.

trans-3- [4- (1,1-Dimethylnonyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane at 69-70 ° C, was prepared from 1.00 g (2.29 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylnonyl) phenyl] cyclohexanol. Yield: 709 mg (89%).

IR (chloroform):

3636, 3413, 1631, 1618 and 1532 cm ^-1 .

Mass spectrum (m / e):

346 (M &lt; + &gt;), 328, 233 and 215.

PMR (deuterochloroform, tetramethylsilane, δ '):

0.87 (multiplet, terminal methyl),

1.22 (singlet, geminal dimethyl),

3.30 (multiplet, meth group of the benzyl residue),

4.22 (multiplet, methine grouping of carbinol residue),

4.98 (broad singlet, hydroxyl),

6.7 to 7.3 (multiplet, proton of aryl residue).

For C25H38O2: calculated: 79.71 ° C, 11.05% H, found: 79.11% C, 10.86% H.

cis-3- [4- (1,1-Dimethyldecyl) -2-hydroxyphenyl] cyclohexanol

This product, melting after crystallization from pentane at 93-94 ° C, was prepared from 2.6 g (5.78 mmol) of cis -3- [2-benzyloxy-4- (1,1-dimethyldecyl) phenyl] cyclohexanol. Yield 2.02 g (98%).

IR (chloroform):

3636, 3390, 1629 and 1587 ^cm-first

Mass spectrum (m / e):

360 (M &lt; + &gt;), 342, 288, 233 and 215.

PMR (deuterochloroform, tetramethylsilane, values <S):

0.83 (multiplet, terminal methyl),

1.20 (singlet, geminal dimethyl),

2.85 (multiplet, meth group of the benzyl residue),

3.75 (multiplet, methine grouping of carbinol residue),

4.4 (broad signal, hydroxyl) a

6.4 to 7.2 (multiplet, proton of the aryl residue).

H, 11.18; Found: C, 80.12; H, 11.39.

trans-3- [4- (1,1-Dimethyldecyl) -2-hydroxyphenyl] cyclohexanol

This product, melting at 76-77 ° C, was prepared from 360 mg (0.80 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethyldecyl) phenyl] cyclohexanol. Yield: 130 mg (45%). IR (chloroform):

3636, 3425, 1631, 1616 and 1580 ^cm-first

Mass spectrum (m / e):

360 (M &lt; + &gt;), 342, 233 and 215.

PMR (deuterochloroform, tetramethylsilane, δ '):

0.86 (multiplet, terminal methyl),

1.22 (singlet, geminal dimethyl),

3.2 (multiplet, meth group of benzyl residue),

4.17 (multiplet, methine carbinol moiety and hydroxyl); and

6.6 to 7.2 (multiplet, proton of the aryl residue).

H, 11.18; Found: C, 80.20; H, 11.27.

cis-3- [4- (1,1-Dimethyundecyl) -2-hydroxyphenyl] cyclohexanol

This product, melting at 85-88 ° C, is prepared from 3.5 g (7.54 mmol) of cis-3- [2-benzyloxy-4- (1,1-dimethylundecyl) phenyl] cyclohexanol. 39 g (85%).

IR (chloroform):

3636, 3390, 1634 and 1592 ^cm-first

Mass spectrum (m / ej):

374 (M &lt; + &gt;), 356, 233 and 215.

PMR (deuterochloroform, tetramethylsilane, values of 5):

0.89 (multiplet, terminal methyl),

1.22 (singlet, geminal dimethyl),

2.98 (multiplet, methine group of benzyl residue),

3.95 (multiplet, methine grouping of carbinol residue),

6.83 (multiplet, proton of aryl residue);

7.09 (doublet, J = 8 Hz, proton of the aryl residue).

For C25H42O2: calculated: 80.15 ° C, 11.30% H, found: 80.00% C, 11.48% H.

trans-3- [4- (1,1-Dimethylundecyl) -2-hydroxyphenyl] cyclohexanol

This product melts at. Mp 73-74 ° C, prepared from 1.00 g (2.16 mmol) of trans -3- [2-benzyloxy-4- (1,1-dimethylundecyl) phenyl) cyclohexanol. Yield: 487 mg (60%).

IR (chloroform):

3636, 3413, 1637 and 1585 ^cm-first

Mass spectrum (m / e):

374 (M &lt; + &gt;), 356, 233 and 215.

PMR (deuterochloroform, tetramethylsilane, δ values):

0.89 (multiplet, terminal methyl),

1.27 (singlet, geminal dimethyl),

3.25 (multiplet, meth group of the benzyl residue),

4.31 (multiplet, methine grouping of carbinol residue),

5.07 (broad singlet, hydroxyl);

6.7 to 7.3 (multiplet, proton of aryl residue).

For C25H42O2: calculated: 80.15 ° C, 11.30% IT, found: 80.11% C, 11.16% H.

cis-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] cyclooctanol

This product, melting after crystallization from pentane at 89-90 ° C, was prepared from 1.36 g (3.11 mmol) of cis-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclooctanol. g (73%).

Mass spectrum (m / e):

346 (M ^& lt ^{; +} & gt ^; ), 328, 261 and 243.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.83 (multiplet, terminal methyl),

1.22 (singlet, geminal dimethyl),

3.0 (broad multiplet, meth group of benzyl residue),

3.98 (broad multiplet, methine grouping of carbinol residue),

6.75 (multiplet, proton of the aryl residue);

7.00 (doublet, J = 8 Hz, proton of the aryl residue).

For C23H38Q2 calculated: 79.91% C, 11.05% H, found: 79.90% C, 10.89% H.

trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] cyclooctanol

This product, melting after crystallization from pentane at 76-77 ° C, was prepared from 4.0 g (9.17 mmol) of trans -3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclooctanol. Yield: 2.62 g (83%).

Mass spectrum (m / e):

346 (M &lt; + &gt;), 328, 261 and 243.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.83 (multiplet, terminal methyl),

1.24 (singlet, geminal dimethyl),

3.15 (broad multiplet, meth group of the benzyl residue),

4.05 (multiplet, methine grouping of carbinol residue),

6.78 (multiplet, proton of aryl residue) and

7.02 (doublet, J = 8 Hz, proton of the aryl residue).

H, 11.05; H, 11.05. Found: C, 79.81; H, 10.86.

Example 3

3- (4- (1,1-Dimethylheptyl) -2-hydroxyphenyl) cyclohex-2-enone

A mixture of 400 mg (0.988 mmol) of 3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclohex-2-enone and 20 mg of 5% palladium on carbon was stirred under a hydrogen atmosphere at 0.1 pressure for 30 min. MPa. After addition of ether, the reaction mixture was filtered through diatomaceous earth and the filtrate was evaporated. The solid residue was recrystallized from petroleum ether to give 110 mg (35%) of the title compound, melting at 122-123 ° C.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.82 (multiplet, terminal methyl in side chain),

1.30 (geminal dimethyl),

2.19 (double triplet, J = 6 Hz and J = 6 Hz, methylene on Cs),

2.52 (triplet, J = 6 Hz, methylene on Cl), 2.80 (triplet, J = 6 Hz, methyl on C6),

6.7 to 7.4 (multiplet, proton of aryl residue and proton of vinyl group);

8.16 (singlet, phenol).

IR (KBr):

3448, 1634, 1608 and 1565 cm ^-1 .

Mass spectrum (m / e):

314 (M &lt; + &gt;), 299 and 229.

H, 9.62; Found: C, 80.23; H, 9.46.

Example 4 trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -5-methylcyclohexanone

A mixture of 175 mg (0.417 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -5-methylcyclohexanone and 175 mg of 5% palladium on carbon containing 50% water in 8 ml of methanol The mixture was stirred in a hydrogen atmosphere at a pressure of 1 bar until the consumption of hydrogen ceased. The reaction mixture was filtered through diatomaceous earth and the filtrate was evaporated under reduced pressure. Crystallization of the residue from pentane gave 89 mg (64%) of the title compound, melting at 99-102 ° C.

Mass spectrum (m / e):

330 (M ^& lt ^{; +} & gt ^; ), 312, 273 and 245.

Example 5 trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -cis-5-methylcyclohexanol

A mixture of 220 mg (0.521 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -cis-5-methylcyclohexanol and 220 mg of 5% palladium on carbon containing 50% water was taken up in 8 ml of methanol. The mixture was stirred under a hydrogen pressure of 1 bar for 3 hours. The reaction mixture was filtered through diatomaceous earth, the filtrate was evaporated and the residue crystallized from petroleum ether. 91 mg (53%) of the title compound melting at 111-112 ° C is obtained.

IR (chloroform):

3571, 3333, 1629 and 1572 ^cm-1

Mass spectrum (m / e):

332 (M &lt; + &gt;), 314, 246 and 229.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.85 (multiplet, terminal methyl),

1.13 (doublet, J = 7 Hz, methyl to Cs),

1.26 (singlet, geminal dimethyl),

3.55 (multiplet, benzyl residue meth group),

4.15 (multiplet, methine grouping of carbinol residue),

5.90 (broad singlet, hydroxyl),

6.90 (multiplet, aryl residue proton); and

7.20 (doublet, J = 8 Hz, proton of the aryl residue).

In a similar manner, the following compounds were prepared from the appropriate starting materials:

cis-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -trans-5-methylcyclohexanol

This product was prepared as an oil from 45 mg (0.107 mmol) of oily cis-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -1H-5-methylcyclohexanol. Yield: 20.0 mg (56%).

High resolution mass spectrum (m / e):

332.2698 (M +, C 22 H 36 O 2), 314.2635, 247.1657, and 229.1600.

trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -trans-5-methylcycloliexanol

This product was obtained in quantitative yield (28 mg) as an oil from 36 mg (0.0853 mmol) of trans -3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -trans-5-methylcyclohexanol.

R f = 0.35 (silica gel, 50% ether in pentane).

cis-3- [4- (1,1-Dimethylphenyl) -2-hydroxyphenyl] -cis-5-methylcyclohexanol

This product was obtained in quantitative yield from 168 mg (0.398 mmol) of cis-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -cis-5-methylcyclohexanol.

Melting point 113-114 ° C.

IR (chloroform):

3636, 3390, 1631 and 1592 cm ^-1 .

Mass spectrum (m / e):

332 (M &lt; + &gt;), 314, 247, 229 and 95.

PMR (deuterochloroform, tetramethylsilane, values of 5):

1.21 (singlet, geminal dimethyl),

2.95 (multiplet, meth group of the benzyl residue),

3.82 (multiplet, methine grouping of carbinol residue),

5.62 (singlet, hydroxyl),

6.82 (multiplet, aryl residue proton); and

7.12 (doublet, J = 8 Hz, aryl residue proton).

H, 10.91; Found: C, 79.79; H, 10.62.

Example 6 trans-3- [4- (1,1-Dimethylheptyl) -2-hydroxyphenyl] -cis-4- (2-propenyl) cyclohexanol

A solution of 900 mg (2.01 mmol) of trans-3- [2-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -cis-4- (2-propenyl) cyclohexanol and 2.74 ml of 2.2M n-butyllithium (in hexane) in 3 mL of ether was stirred at room temperature for 2 days, then an additional 2.0 mmol of n-butyllithium was added and stirring was continued for 2 days and the reaction mixture was added to 250 mL of saturated ammonium chloride solution. The mixture was extracted with ether, dried (MgSO4) and evaporated and the residue purified by column chromatography (20 g silica gel, 50% ether / pentane) to give 631 mg (88%) of the title compound. m.p. 85-91 ^° C.

IR (chloroform):

3311, 1639, 1618 and 1567 ^cm-first

Mass spectrum (m / e):

358 (M &lt; + &gt;), 343, 340, 316, 299, 273 and 255.

PMR (deuterochloroform, tetramethylsilane, hodnoty values):

0.82 (multiplet, thyminal methyl),

1.28 (singlet, geminal dimethyl),

3.02 (multiplet, meth group of the benzyl residue),

4.23 (multiplet, methine grouping of carbinol residue),

4.6 to 5.0 and 5.4 to 6.0 (multiplet, vinyl residue proton),

6.81 (doublet, J = 2 Hz, proton of the aryl residue),

6.82 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.05 (doublet, J = 8 Hz, proton of the aryl residue).

Using 500 mg (1.12 mmol) of cis-3- [2-benzyloxy-4- (1,1-dimethylheptyl-phenyl) -tris-4- (2-propenyl) -cyclohexanol, 500 mg (241 mg) was prepared. (60%) also cis-3- [4- (1,1-dimethylheptyl) -2-hydroxyphenyl] -tris-4- (2-propenyl) cyclohexanol.

Melting point after crystallization from pentane 124-125 ° C.

IR (chloroform):

3571, 3333, 1642, 1618 and 1580 ^cm-first

Mass spectrum (m / e):

358 (M &lt; + &gt;), 340, 298, 286, 273 and 255.

PMR (deuterochloroform, tetramethylsilane, values <5):

0.83 (multiplet, thyminal methyl),

1.23 (singlet, geminal dimethyl),

3.70 (multiplet, methine grouping of carbinol residue),

4.6 to 5.1 and 5.2 to 6.0 (multiplet, vinyl residue proton),

6.70 (doublet, J = 2 Hz, proton of aryl residue),

6.82 (double doublet, J = 8 Hz and J = 2 Hz, proton of the aryl residue);

7.05 (doublet, J = 8 Hz), proton of the aryl residue).

For C24H38O2: calculated: 80.39% C, 10.68% H, found: 80.52% C, 10.57% H.

Claims (2)

Process for the preparation of 3- (2-hydroxy-4-substituted-phenyl) -cycloalkanones and cycloalkanols derivatives of the general formula: R2 represents a hydrogen atom, a C1 -C6 alkyl group, a C1 -C6 alkenyl group, a phenyl group or a C1 -C4 phenylalkyl group in the alkyl moiety, R3 represents a hydrogen atom or a methyl group, Z is C 1 -C 13 alkylene or a radical of formula - (alkjn, -O- (alk _{2) n} -, wherein (a alkij (alka) are each an alkylene group having 1 to 13 carbon atoms, with the proviso that the sum of carbon atoms in (alk) + (alkz) does not exceed than 13, aman is always 0 or 1, W represents a hydrogen atom, a pyridyl group or a radical of formula wherein W 1 represents a hydrogen, fluorine or chlorine atom, A represents a hydrogen atom and B represents a hydroxy group, a hydroxymethyl group or an alkanoyloxy group having 1 to 5 carbon atoms, or A and B together form an oxo, methylene or C 2 -C 4 alkylenedioxy group, Rd represents a hydrogen atom or a (C1-C6) alkyl group and n is 0, 1, 2, 3 or 4, provided that if n is 0, then R4 represents a hydrogen atom, characterized in that of the general formula in which Q represents a phenolic hydroxyl function protecting group and the remaining general symbols are as described above, in a manner known per se cleaving the phenolic hydroxyl function protecting group Q. 2. The process of claim 1 wherein the protecting group of the phenolic hydroxyl function of Q is benzyl or substituted benzyl, and is cleaved by hydrogenation in the presence of palladium on carbon catalyst.