JPS608238A - Manufacture of cycloalkenyl alkines - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing cycloalkenylalkynes, which is particularly suitable for the production of cycloalkenylalkynes. The invention also relates to novel intermediates in this process.

The method provided by the present invention is characterized by the general formula, where n is the number O
or 1; one of the symbols R1 and R2 represents hydrogen and the other represents hydrogen, a hydroxy or oxo group or a protected hydroxy or oxo group, and R
3 represents hydroxy, an oxo group, =CH-CH2-OH or =CH-CHO or a group derived from these 1 with a protected hydroxy or oxo functional group; R4 is -Co-OR6,- Co-R6, -Co-NR' R7, -GO-CL or =so2-
and R6 and R7 represent saturated or aromatic hydrocarbon radicals, or R7 also represents hydrogen, by cleavage of R'OH, in which n, R
1, R2 and R3 are converted into a compound having the meaning of 11, and optionally R1.

It is characterized in that a compound of formula 11 in which R2 or R3 has a protected hydroxy or oxo group is hydrolyzed to the corresponding hydroxy or oxo compound.

As used herein, the term "protected hydroxy or oxo group" or "protected hydroxy or oxo functional group" includes protecting groups commonly used for alcohols and ketones or aldehydes. . Preferred protected hydroxy groups are ether, silyl ether and acetal groups containing up to 7 carbon atoms, such as methoxy, ethoxy, benzyloxy, trimethylsilyloxy, (2-methoxy-2-propyl)oxy and the like. Preferred protected oxino, ( is an acetal or ketal group containing up to 10 carbon atoms, especially a group in which the oxo group is ketalized or acetalized with an alkanol or alkanediol. In a particularly preferred embodiment, "protected" Oxo group
The term represents two methoxy or ethylenedioxy groups.

The term "saturated or aromatic hydrocarbon group" preferably includes alkyl, aryl, arylalkyl and alkylaryl groups containing up to 10 carbon atoms. Examples of these groups are methyl, ethyl, phenyl, tolyl and the like.

In accordance with the present invention, it has been found that compounds of formula I can be converted into pure compounds of formula II in good yields under relatively mild conditions.

The preparation according to the invention of the compounds of the formula IT can be carried out in a manner known per se by cleaving the R' OH in the compounds of the formula I by heating and/or in the presence of a catalyst. li3! I-I catalysts are, for example: a) organic nitrogen bases, especially primary and secondary nitrogen bases (such as imidazole, 1,2
．． b) salts of organic nitrogen bases with strong acids (preferably vinegar with a pKa of 1), especially monochlorides, bromides and tosylates (e.g. pyridinium p-tosylate), C) phosphonium salts (e.g. I・
Riphenylphosphonium chloride or bromide)
, d) Acids, preferably with pKa<1, such as toluenesulfonic acid, Amberlys i□
t) A 150 (FlukaAG), hydrochloric acid, sulfuric acid], e)) Realkylchlorosilane (e.g. trimethylchlorosilane), f) Lithium salts, e.g. strong (p K
a < 1) butylic lithium salts (e.g. lithium chloride,
lithium perchlorate, lithium boron tetrafluoride), and g) palladium-(0) catalysts (for example by addition of palladium acetate).

The reaction temperature depends, inter alia, on the meaning of the radical R4 and on whether the reaction is carried out in the presence or absence of a catalyst. The required reaction temperature is generally below 200°C; however, in some cases the cleavage of R40H occurs at room temperature. Pressure is not critical. Therefore, this process 1 is also preferably carried out under atmospheric pressure.

The conversion of compounds of formula I into compounds of formula II according to the invention is advantageously carried out in inert organic solvents, such as ethers, alcohols, nitriles, amides or saturated, aromatic or chlorinated hydrocarbons. Examples of preferable solvents include diethyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, diethyl 1/glycol dimethyl ether, triethylene glycol dimethyl ether, methanol, acetate nitrile, dimethylformamide, Δxane, I toluene, benzene, xylene',
Examples include methylene chloride, dichloroethane, etc.

The process provided by the present invention can be carried out in the presence or absence of a catalyst. When the process is carried out in the presence of a catalyst, the catalyst can be used in catalytic or higher amounts. Preferred catalysts are organic nitrogen bases, their bases and lithium salts.

Hydrolysis of the resulting compounds of formula (1) in which R1, R2 or R3 carries a protected hydroxy or oxo group can be carried out according to methods known per se for the hydrolysis of protective groups.

A further preferred variant of the method provided by the invention is:
It consists of reacting a compound of formula 1 in which R8 represents the group ═CH-CH20H in the presence of equimolar or higher amounts of a phosphonium salt, preferably triphenylphosphonium chloride or bromide. According to this variant, the corresponding compound of formula II is first formed, which is then converted directly into the corresponding phosphonium salt [i.e. the hydroxy group in R3 is converted to a phosphonium salt, e.g. -p (Ca Ha ) s is converted to C18 or -p(C6Ha)g@Brθ].

According to the method provided by the present invention, preferably n
represents the number 0 and R2 represents hydrogen or n represents the number 1, compounds of formula I are used. In a particularly preferred embodiment, n in formula I represents the number l;
And R1 represents hydrogen. Furthermore, in principle, the symbol R1
and compounds of formula I in which one of R2 represents hydrogen and the other represents hydrogen or hydroxy, in particular hydroxy, for example n represents the number 1, R1 represents hydrogen, and R
Preference is given to compounds of formula I in which 2 represents hydroxy.

Particularly preferred groups represented by R3 are hydroxy and the group =CH-CH2,OH. In addition, the optional double bond in R3 preferably has a generally trans configuration.

A particularly preferred group represented by R4 in formula I above is the group -CO-ORB, especially a group in which R6 represents C1-C6-alkyl.

Particularly preferred groups are 100-0CR and -00-0C2
It is H6. Another preferred group represented by R4 in formula 1 above is the group -Co-OR', especially a group in which R6 represents an aromatic hydrocarbon group (eg benzoyl).

In principle, the hydrogen atom at the 5-position of the cyclopentyl ring or the 6-position of the cyclohexyl ring and the QR40- are mutually cis-position M[syn elimination (elimination).
) ] Compounds of formula 1 are further preferred.

A further preferred variant of the process provided by the invention is a general formula in which R5 represents hydroxy or the group =CH-CH2-0I, and R4 has the meaning given above.

or its optical enantiomer by cleavage of R40H in the presence of a sterically hindered basic lithium compound, wherein R5 has the above meaning.

or its optical enantiomer.

The term "sterically hindered basic lithium compound" refers to a sterically hindered basic lithium compound having a steric hindrance on the basic group (nucleophil-ic attack on the group -0R4).
) at least one 9. Preferably lithium-organic compounds derived from organic compounds having a pKa value of at least 11 are included. For example, steric hindrance is
This can be done by branching or substitution at the carbon atom in the - position or by substitution in the 0-position of the benzene ring. Among such compounds, preferred are alkyl lithiums, lithium alkalates, and lithium alkalates that satisfy the above conditions.
Lithium ferulate, lithium dialkylamide, etc.
For example, lithium tert, butyrate, lithium 1.
1=dimethylpentalt, lithium 2,6-dimethylfelt, lithium 2,6-di(tert, butyl)
ferulate, lithium 2.6-cyclofert,
tert, butyllithium, 2,6-di(tert, butyl)phenyllithium, and lithium diisopropylamide.

In this variant, preferably at least about 2 moles of lithium compound are used per mole of compound of formula Ia (or its enantiomer). In particularly preferred embodiments, about 2 to 3 molar equivalents of lithium compound are used, although larger amounts can be used without deleteriously affecting the reaction.

The temperatures, pressures and solvents mentioned above in connection with the reaction of compounds of formula I can likewise be applied to this variant. However, this variant is preferably carried out at temperatures of about 40°C to about 70°C. Saturated and aromatic hydrocarbons are particularly preferred solvents.

This variant gives high yields. Furthermore, the configuration of the double bond that may optionally be present in R5 is preserved. Furthermore, since generally only the compound of formula I and its optical counterpart (but not the remaining stereoisomers) reacts satisfactorily under the mild temperature conditions described above, this variant does not allow the preparation of pure isomeric compounds. It is particularly suitable for manufacturing.

-1-R6 in formula Ia is preferably a group =CH-C
Represents H2-OH. The double bond in this group is preferably present in the trans configuration. Preferred groups represented by R4 are -Co-R' and especially -〇〇-0
It is R6. Particularly preferred among such groups are COOCH3, COOC2H5, -Go-C,H, and -Co-CH.

The compounds of formula I are new and also form part of the invention. This compound can be prepared in a manner known per se, for example by the corresponding lithium alcohol-1
- (compounds of formula I in which R' represents lithium), from the corresponding chlorides, i.e. of the formula Cl-Co-0R', CI-C
o-R', CI-Co-NR' R? , C1-CO-C
I or Cl-3o2-R', (+,!LR' and R
7 can be prepared by reaction with a compound having the above meaning. The thiium alcoholate required for this reaction can be obtained in a manner known per se by reacting the corresponding cyclopentanone or cyclohexanone with the corresponding alkynyllithium. Hydroxy and oxo groups which may also optionally be present in this case are preferably present in protected form. These protecting groups can be cleaved, if desired, before or after the introduction of the group R4, or only after the cleavage of R40H in the present invention.

The conversion of compounds of the formula II into carotenoids can be carried out in known manner or in a manner known per se, for example by conversion into the appropriate aldehyde or phosphonium salt and subsequent subjecting to a Wt t t i g reaction. .

The present invention also covers all novel compounds as described herein,
Concerning mixtures, manufacturing methods and uses.

The present invention will be explained in more detail by the following examples.

Example 1 Ethyl (is, 4R,6R')-4-hydroxy-1
,-(3-hydroxy-1-butynyl)-2゜2.6-
Trimethylcyclohexyl carbonate 10.14g
was dissolved in 50 ml of hot dimethylformamide. The solution was treated with pyridinium p-l sylate Ig and the Jtt reactor was stirred in a preheated oil bath for 1.5 hours (oil bath temperature 90-93°C, internal temperature about 79-82°C). The mixture was then poured into 500 ml of half-saturated, dihydrated sodium solution and extracted three times with 200 ml each of diethyl ether. The organic phase was washed once with saturated sodium chloride solution, dried over sodium sulfate and evaporated. The crude product obtained (8.3 g) was chromatographed on silica gel with hexane/diethyl ether (volume ratio i:t). Thus, (4R)-
4-(4-hydroxy-2,2,6-drimethyl-1-
cyclohexenyl)-3-butyn-2-ol 5-9 g
(83.3%) was obtained.

Ethyl (13,4R,6R)-4 used as starting material
-Hydroxy-1-(3-hydroxy-1-butynyl)
-2,2,6-)limethylcyclohexyl carbonate was prepared as follows: a) In a four-eye flask equipped with a magnetic stirrer, a thermometer, a dropping funnel and an inert gasifier, (4R ,6R)-4-hydroxy-2,2,6-
19.52 g of 1-dimethylcyclohexanone was added to 40 ml of anhydrous tetrahydrofuran and 2 ml of pyridinium Pi sylate.
0 mg of the mixture under argon and then 14-4 g of isopropyl methyl ether was added dropwise to this solution within about 20 minutes at 15-20°C. The obtained solution A is ff
Processed as described in ic).

b) A solution of 23.5 g of 3-butyn-2-yltrimethylsilyl ether in 80 ml of anhydrous tetrahydrofuran in a sulfonation flask equipped with a stirrer, a thermometer, a dropping funnel riser and an inert gasifier under argon. and cooled to -30°C, then heated at -30°C to 20°C for 10
Within minutes, approximately 1,56% of butyllithium in hexane
It was treated dropwise with 105 ml of MmI. Add this mixture to 1
Stirred for a further 30 minutes at 0°C, then cooled again to -40°C. The resulting solution B was treated as described in IIC).

C) Solution A was added dropwise to solution B within 10 minutes at -4.0°C. The mixture was stirred for a further 30 minutes and then treated with 15.7 ml of ethyl chloroxate and the mixture was allowed to warm to room temperature within 1 hour while stirring.

The mixture was then cooled to O'C and, with stirring, added 1 part of 3N sulfuric spirits.
00 ml and further 30 min at 0-5 °C (1~)
! Stirred. The mixture was diluted with 250 ml of ethyl acetate and the aqueous phase was separated. Add 250ml each of ethyl acetate to the aqueous phase.
It was back-extracted twice. The organic phase was washed three times with 250 ml each of saturated sodium carbonate solution and once with 250 ml of saturated sodium chloride solution, combined and dried over sodium sulfate. After filtering off the desiccant and concentrating the filtrate in a rotary evaporator (water bath temperature +11i50 °C), 43.6 g of crude product were obtained, which was dissolved in silica gel in hexane/diethyl ether (volume ratio 1). : l
) was chromatographed. From the fractions containing the product, a total of 36.5% was obtained as a slightly yellowish oil.
g (97,8%) of ethyl(is,4R,6R)-4
-Hydroxy-1-(3-hydroxy-1-butynyl)
-2,2,61-limethylcyclohexyl carponate was obtained.

Example 2 In a corroflask equipped with a magnetic stirrer, a thermometer, a reflux condenser and a headpiece to argon, 6.7 g of imidazole are dissolved in 40 ml of triethylene glycol dimethyl ether under argon and the solution is dissolved. Heated to 195°C in an oil bath. Next, noethyl (t) in 15 ml of triethylene glycol dimethyl ether
s, 4R, 5R)-4-hydroxy-1-(5-hydroxy-3-methyl-3E~penten-1-ynyl)-2
, 2,6-dolinotylcyclohexyl carbonate8.
0 g of solution was added dropwise within 60 minutes at an internal threat temperature of 188-190°C. The mixture was kept at the same temperature for a further 30 minutes and then poured into 200 ml of ice/water. The aqueous phase was extracted twice with 250 ml each of diethyl ether. The combined ether phase was washed 4 times with 10ml of sphagnum moss, dried over 42ml of sodium sulfate, condensed in a rotary evaporator at about 50°C, and then condensed in a high vacuum at room temperature. It was dried for 3 hours. The purified crude product (0.6 g) was chromatographed on silica gel L with diethyl ether/hexane (volume ratio 1: l), < L, teya (F).
The reason for the yellow color is (4R)-5~(4-hydroxy-2,2,6-l.rifthyl-1-cyclohexenyl)
-3-methyl-2-penten-4-yn-1-ol 3
．． 5 g (61.4%) could be isolated (ratio 2E
/2Z=91, 0:4.

7).

Ethyl (Is, 4R) used as starting material.

6R)-4-hydroxy-1-(5-hydroxy-3-
Methyl-3E-penten-1-ynyl)-2,2,6-
) Limethyl cycloha, xyl carbonate was produced as follows.

a) In a four-eye flask equipped with a 1fi stirrer, a thermometer, a dropping funnel and an inert cassifier, (4R, 6R)
-4-Hydroxy-2,2,6-)limethylcyclohexanone (52.0 g) was dissolved in tetrahydrofuran (6 g) under argon.
5ml and pyridinium silane i 50mg
This solution was treated dropwise with 48.0 g of impropenyl methyl ether within 20 minutes at 15-200 G. #! The yellow solution A was treated directly as described in section C).

b) 5-(2-methoxy-2-
Propyl)oxy-3-merinoa~3E-pentene-1
A solution of 79 g of -in was added to Albond, and -20
Cooled to °C.

This solution was treated dropwise within 20 minutes at -30°C to 20°C with 2.80 ml of a solution of about 1,56M bunallithium in hexane, and the diluted mixture was stirred for an additional 30 minutes.
I stirred it. flf orange solution Bfciijc)
directly processed as described in .

C) Solution B was treated dropwise with solution A within 20 minutes at -15[deg.]C and the mixture was stirred for a further 30 minutes at room temperature. The mixture was cooled to -20'C and treated with 42 tnl of ethyl chloroxate with stirring, then the 41g mixture was allowed to warm to room temperature over 1 hour.

The lfi compound was then diluted with 250 ml of diethyl ether and the aqueous phase was backwashed with 250 ml of diethyl ether. b) Add 250 ml of saturated sodium chloride solution to 2
The mixture was washed twice, combined, and dried over sodium sulfate-E. The desiccant was filtered off, and the filtrate was condensed with a rotary evaporator (water bath temperature: 50
℃), the crude ethyl (is
,4R,6R)-4-(2-methoxy-2-propyl)
Oxy-1-[5-(2-methoxy-2-propyl)oxy-3-methyl-3E-penten-1-ynyl]-2
,2゜6-drimethylcyclohedylcarbo, lT, -
1.5 g of +-tg was obtained.

d) Add 450 m of tetrahydrofuran to the rubbed brown-yellow oil.
1 and pA solution in 50 ml of water), treated with 2 g of pyridinium p-)sylate and stirred for a further 20 minutes (clear solution). This brown-yellow oil solution was then treated with 2 g of solid potassium carbonate and evaporated to constant weight in a 1-5 rotary evaporator (bath temperature 50 DEG C.). The residue was diluted with 250 ml of diethyl ether and extracted with 250 ml of water. The aqueous phase was separated and back-extracted with 250 ml of diethyl ether. The organic phase was saturated with sodium chloride L, each solution was 250 m
The mixture was washed twice with 200ml of sodium sulfate, combined and dried with 200ml of sodium sulfate. After filtering off the desiccant and e-condensing the filtrate in a rotary evaporator (water bath temperature 50° C.), 140 g of a crude product was obtained, which was poured onto silica gel in a diethyl ether/hexane C'3 ratio of 1: Chromatographed by l). The product-containing fractions yielded pure ethyl(is,4R,6R)-4-hydroxy-1-(5-hydro-3-methyl-3E-menthen-l-ynyl)-2,2 as a slightly yellowish oil. ,6-drimethylcyclohexylcarpone'Total 99,0 g (:91.6
%) was (1t).

Example 3 In a bilo flask equipped with a m/A stirrer, a reflux condenser and an argon henode piece, 4.4 g of imidazole are dissolved in 50 ml of triethylene glycol dimethyl ether under argon and the solution is heated to 195 ml in an oil bath. heated to ℃. Next, triethylene glycol dimethyl ether 10
Ethyl 1-(5-hydroxy-3-methyl-3 in ml
A solution of 5 g of E-penten-1-ynyl)-2,2,6-drimethylcyclohexyl carbonate was heated to an internal temperature of 18
It was added dropwise within about 20 minutes at 5-190°C. The mixture was kept at the same temperature for a further hour and then poured onto 200 ml of ice/water. The aqueous phase was diluted with 250 ml each of diethyl ether.
Extracted twice. Pour the combined ether phase into a 100ml water cup.
The crude product (3 , 6 g) with silica gel in diethyl ether/hexane (volume ratio l:
1) was subjected to chromatography. The product-containing fractions yielded 5-(2,
6,6-1-dimethyl-1-cyclohexenyl)-3-
2.1 g of methyl-2-penten-4-yn-1-ol
(59.5%) was obtained.

(Ratio 2E/2Z=98.8: O', 6).

Ethyl 1-(5-hydroxy-3
-Methyl-3E-penten-1-ynyl)-2,2,6
-19 Methylcyclohexylcarpo-1. methoxy-2-propyl)oxy-3-
115.1 g of methyl-3E-penten-1-yne and 90 ml of tetrahydrofuran are charged, the 7Hj compound is cooled to -25°C, and at this temperature a 1°6M solution of butyllithium in hexane is added dropwise within 20 minutes. Processed. The mixture was stirred for a further 15 minutes at 0°C, then cooled to -10'C and treated dropwise at this temperature within 15 minutes with 72.9 g of 2.2.6-1-limethylcyclo, gisanone. The mixture was then warmed to room temperature and stirred for a further 2 hours. This 1j
The mixture was cooled to O'C and treated dropwise at this temperature within 15 minutes with 67.5 ml of ethyl chloroxate, allowed to warm to room temperature and stirred for a further 1.5 hours. The mixture was then poured into 11 parts of saturated sodium bicarbonate solution and extracted twice with 11 parts each of diethyl ether. Remove the organic phase with deionized water 11
The desiccant was filtered off and the filtrate was concentrated under vacuum on a rotary evaporator (bath temperature approx.
5℃). The 5-(2-methoxy-2-propyl)oxy-3-methyl-3E-penten-1-yne was removed from the residue under high vacuum at a bath temperature of 60°C for 1 hour.

232.1 g (117 , 3%), which was processed directly without further purification.

b) Dissolve 105.5 g of the crude product obtained as described in paragraph a) above in 630 ml of tetrahydrofuran in a sulfonation flask equipped with a stirrer, thermometer and Alyne headpiece and add this solution. deionized water 10
5 ml and 5.25 g of pyridinium p-tosylate and the mixture was stirred for a further 30 minutes at room temperature. This mixture was poured into 750 ml of feed sodium bicarbonate solution and extracted three times with 600 ml each of diethyl ether.

Add 750 ml of half-saturated sodium hydrogen carbonate solution to
Wash with t'f+L, dry over sodium sulfate, filter off the desiccant, and transfer the solution under vacuum to a rotary evaporator (bath temperature approx.
℃). After drying under high vacuum, 84.8 g (116.9%) of the crude product was chromatographed on silica gel with hexane/diethyl ether (volume ratio ?=1). Thus, 5-(2,6°6-drimethyl-1-cyclohexenyl)-3-methyl-2-penten-4-yn-1-
2.3 g (4,5%) of ol and ethyl 1-(5-hydroxy-3-methyl-3E-penten-1-ynyl)-
2,2,6-drimethylcyclohexyl carbonate 5
3.6 g (73.9%) was obtained.

Example 4 A tert in a sulfonation flask equipped with a stirrer, a thermometer, a dropping funnel, a reflux condenser and an inert gasifier;
, 16 ml of butanol and 20 ml of anhydrous toluene were charged under argon and cooled to -2500. This solution was treated dropwise within 10 minutes at -30 DEG C. to -20 DEG C. with 25 ml of a 1.56 M solution of butyllithium in hexane, and the mixture was stirred with cooling for a further 30 minutes.

A solution of the lithium tert, butyrate thus prepared was then added (lS,
4R,6R)-4-hydroxy-1-(5-hydroxy-3-methyl-3E-penten-1-ynyl)-2,2
, 6-1 linotylcyclohexylbenzony) 14.4
g solution was added all at once. The resulting suspension was carefully heated to 65° C. by means of an oil bath and stirred at this temperature for 1.5 hours. The mixture was then poured onto 150 ml of ice/water. The aqueous phase was separated and extracted twice with 150 ml each of diethyl ether. The organic phase was dissolved in saturated sodium chloride solution 150
ml, combined and dried over sodium sulfate, concentrated on a rotary evaporator at about 40° C., and then the residue was dried in a high vacuum at room temperature for 1 hour.

71) The obtained crude product (tz, og) was dissolved in diethyl ether/hexane (volume ratio 1:1) on silica gel.
Chromatography was carried out by From the fraction containing the product, (4R)-5-(
4-Hydroxy-2,2,6-dolinothyl-1-cyclohexen-1-yl)-3-methyl-2E-pentene-
A total of 7.5 g (80%) of 4-yn-1-ol was obtained (purity 98.8%, 2Z isomer content 1.1%).

(IS, 4R, 6R)-4-hydroxy-1-(5-hydroxy-3-methyl-3E-menthen-1-ynyl)-2,2°6-drimethylcyclohexylbenzoate used as a starting material was Prepared as follows: a) (4R16R in 20 ml of tetrahydrofuran)
)-4-Hydroxy-2,2,6-1-limethylcyclohexanone 16.4g and pyridinium p-+.silley'
A solution of 30 mg p was heated at 15-20° under argon.
Impropenyl methyl ether 16. within 10 minutes at C.
Dropwise treatment was carried out at 0g.

b) A solution of 27 g of 5-(2-methoxy-2-propyl)oxy-3-methyl-3E-penten-1-yne in 30 ml of anhydrous tetrahydrofuran is heated under argon to -20 ml of anhydrous tetrahydrofuran.
C. and then treated dropwise within 10 minutes with 90 ml of a 56M solution of butyllithium in hexane at -30.degree. C. and 20.degree. C., and the mixture was stirred for a further 30 minutes.

c) The solution obtained as described in h ftTb) -
Within 15 minutes at 15°C, the solution prepared as described in section a) was added dropwise to F, IL, and the mixture was stirred for a further hour at room temperature. The mixture was cooled to -10'0 and treated with 18.6 ml of benzoyl chloride with stirring,
It was then stirred overnight (18 hours) at room temperature. The mixture was then poured into 200 ml of saturated sodium bicarbonate solution,
Separate the aqueous phase.

Back extraction was carried out twice with 300 ml each of diethyl ether. The organic phase was washed twice with 250 ml each of saturated sodium chloride solution, concentrated, dried over sodium sulphate and the drying agent was filtered off. After concentrating the filtrate on a rotary evaporator (water bath temperature 40 °C), the crude (IS, 4R, 6R) was obtained as a brown-yellow oil.
)-41(2-medoxy-2-propyl)oxy-1-
[5-(2-methoxy-2-propyl)oxy-3-methyl-3E-penten-1-ynyl]-2,2°6-drimethylcyclohexylbenzoate is obtained. d)
b) Convert the brown-φ colored oil into 400% tetrahydrofuran.
The solution was treated with pyridinium p-1 sylate Ig and stirred for 15 minutes (clear solution). The mixture was then passed into 200 mX of saturated sodium bicarbonate solution, the aqueous phase was separated and extracted twice with 300 ml each of diethyl ether. The organic phases were combined overnight, dried and smoked with 1/2 sulfuric acid, and the desiccant was filtered off.

After concentrating the filtrate on a rotary evaporator (bath temperature 40 °C), 51.3 g of the crude product was obtained, which was chromatographed on silica gel-1 with diethyl ether (volume ratio 2:1). . From the fraction containing the product, pure (Is,4R,6R) was obtained as a pale yellow oil.
-4-Hydroxy-1-(5-hydroxy-3-methyl-3E-penten-1-ynyl)-2.2.6-drimethylcyclohexylbenzoate Total 37.

2g (86.1%) was obtained.

Example 5 A tert. tert.
40 ml of Buknol and 50 ml of anhydrous toluene were charged under argon and cooled to -25°C. This solution was mixed with 1 part of butyllithium in hexane at 30°C to 20°C within 30 minutes.

It was treated dropwise with 130 ml of a 56M solution and the mixture was stirred for a further 30 minutes while cooling. The thus produced lithium tert. Butyrate solution at 6℃
Ethyl (IS) in 150 ml of anhydrous toluene at
, 4R. 6R)-4-hydroxy-1-(5-hydroxy-3-methyl-3E-penten-l-ynyl)-2
．． 2. A solution of 32.4 g of 6-1-limethylcyclohexyl sulfonate (prepared according to Example 2) was added at a time. Carefully remove this #i self-compound using an oil bath.
℃ and stirred for 30 minutes using this Tomisho. The mixture was then poured into 400 ml water/water. The aqueous phase was separated and extracted twice with 300 ml each of diethyl ether. The organic phases are washed with 300 ml of saturated sodium chloride solution, combined, dried over sodium sulfate and concentrated on a rotary evaporator at about 40° C., and the residue is then concentrated under high vacuum at room temperature. It was dried for 5 hours. Thus (4R)-5-(4-hydroxy-2,6.61-limethyl-1-cyclohexenyl)
-3-methyl-2-penten-4-yn-1-ol (
2Z isomer 1.

23.9 g (102-1%) of a yellow-orange crystalline product containing 90.5% of the 2E isomer with 4% of
This was chromatographed on silica gel with diethyl ether/hexane (1:1 by volume). From the fraction containing the product, (4R)-5-(4-hydroxy-2.6.6-l.
riftyl-1-cyclohexen-1-yl)-3-methyl-2E-penten-4-yn-1-ol (purity 98
．． 0%, 2z isomer content o, 5%) total 19.9 g (
85%) was obtained.

4k Permit m1 Person F Hoffmann Fist und Φ Konhani Akchen Gesellschaft Continuation of page 1 ■ Int, C1,' Identification code Internal reference number C07
C1751006561-4H //B 01 J 31102 102 7059-4
G priority claim @ October 13, 1983 ■Switzerland (C
H)■5583/83-2 0 Inventor Milan Soukup Switzerland 4332 Stein Blumenbeek (no street address) 0 Inventor Erich Widmer Switzerland 4142 Münchenstein Mitzilbeek 47

Claims (1)

[Claims] 1. In the general formula, n represents the number O or l; symbols -R1 and R2
one represents hydrogen and the other represents hydrogen, hydroxy or oxo group, or protected hydroxy or oxo group; R3 is hydroxy, oxo group, =CH
-CH2-OH or =CH-CHo or these groups with a protected hydroxy or oxo functional group; -R'', -〇〇-NR6R?, -Co-CI or -5o2-Re; and R6 and R7 represent a saturated or aromatic hydrocarbon group, or R7 also represents hydrogen; By cleavage of R' OH, the compound can be converted into a compound of the general formula: n,
R', R2 and R3 have the meanings given above, and optionally a compound of formula II in which R1, R2 or R3 has a protected hydroxy or oxo group is converted into a compound of formula II with the corresponding hydroxy or oxo group. A method for producing cycloalkenyl alkynes, which comprises hydrolyzing them into compounds. 2. The method according to claim 1, wherein the cleavage of R40H is carried out by heating. 3. The method according to claim 1 or 2, wherein the reaction of the compound of formula 1 is carried out in the presence of a probe. 4. The reaction is carried out in the presence of an organic nitrogen base or a salt of such a base or a lithium salt, preferably imidazole, 1.2.4-triazole, aniline, pyridinium p-tosylate, lithium chloride, lithium peroxide. , lithium tert. 4. A process according to any one of claims 1 to 3, carried out in the presence F of lithium butyrate or borotetrafluoride. 5.Formula I in which n represents Gl and R1 represents hydrogen
The method according to any one of claims 1 to 4, using the compound. 6. Process according to any one of claims 1 to 5, using a compound of the formula 1 in which one of the symbols 1 and R2 represents hydrogen and the other represents hydrogen or hydroxy, preferably hydroxy. 7. The process according to any one of claims 1 to 6, using a compound of formula I in which R3 represents hydroxy or the group =CH-CH2-OH. 8. In the general formula, R5 represents hydroxy or the group =CH-CH2-OH. =CH-CH2-OH17, and R4 has the meaning given in claim 1, or its optical counterpart in the presence of a sterically hindered basic lithium compound. The reaction method according to any one of claims 1 to 7. 9. R4 is the formula -〇〇 = CR8 or -CO-R6
group, preferably -CO-OCH3, -C0-OC2R
5 or 100-C6H, the method according to any one of claims 1 to srs+, using a compound of formula (1) or Ia representing 5 or 100-C6H. 10. In the general formula, n represents the number 0 or 1; one of the symbols R1 and R2 represents hydrogen; R3 is hydroxy, oxo group, =CH
-CH2-OH or =CH-CHo or protected hydroxy represents a group derived from these groups with an oxo function, R4 is -Go-ORB, -C
o-R', -CO-NR6R7, -CO-C1 or -3O2-R
'; and R6 and R7 represent a saturated or aromatic hydrocarbon group, or i? also represents hydrogen, a compound of.