JPH0526796B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel method for producing cyclohexenone derivatives, namely astaxanthin and intermediates in the synthesis of astaxanthin. The invention also relates to novel intermediates in the process. The method provided by the present invention has the general formula In the formula, n represents the number 0, and x is a group

[Formula], or n represents the number 1 and x represents 6,11-dimethylhexadeca-2,4,6,8,10,12,14-heptaene-2,15-diyl group, The symbols R ¹ have the same or different meanings and represent an alkyl group, and the symbol R ² represents a trialkylsilyloxy group -OSi(R ¹ ) ₃ or an ether group. Oxidation with acid and, if necessary, the resulting general formula In the formula, n, x and R ¹ have the above meanings, and α-siloxyketone of the general formula In the formula, n represents the number 0, and Y is a group

[Formula] or n represents the number 1 and Y represents a 6,11-dimethylhexadeca-2,4,6,8,10,12,14-heptaene-2,15-diyl group, and R ³ represents a hydroxy group or an ether group, which consists of hydrolysis to α-hydroxyketone of . The term "alkyl group" as used herein specifically includes alkyl groups containing from 1 to 20 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, decyl, octadecyl, etc. do. Preferred alkyl groups are those containing 1 to 5 carbon atoms. Examples of trialkylsiloxy radicals -OSi(R ¹ ) ₃ are triisopropylsiloxy, octadecyl-dimethylsiloxy and especially trimethylsiloxy and tert-butyl-dimethylsiloxy. The term "ether group" as used herein includes ether groups commonly introduced for the protection of hydroxy groups. Preferred ether groups are alkoxy groups containing 1 to 5 carbon atoms, especially methoxy groups. In the above formula ~, n is preferably the number 1
and X or Y preferably represents the formula 6,11-dimethylhexadeca-2,4,6,
Represents an 8,10,12,14-heptaene-2,15-diyl group. Furthermore, in the above formulas, n preferably represents the number 0, and X or Y preferably represents the group

Represents [formula]. Conventionally, astaxanthin could be produced from canthaxanthin only in low yields via astacin and kurtaxanthin [J.Chem.Soc.
Chem.Commun.49 (1967)]. The method provided by the present invention is a method for easily obtaining astaxanthin from canthaxanthin or an intermediate in the synthesis of canthaxanthin. Oxidation of the compound of formula using percarboxylic acid,
It can be carried out under conditions commonly used in epoxidation. In this case, the epoxidation of the silylated enol group and the 1,4-
It is presumed that the migration causes the opening of the epoxide ring. Examples of suitable percarboxylic acids are monoperphthalic acid, peracetic acid, perbenzoic acid, m-chloroperbenzoic acid, p-nitro-perbenzoic acid, permaleic acid, and the like. Peracetic acid, perbenzoic acid and especially monoperphthalic acid are preferred percarboxylic acids. Partial hydrolysis of the reaction mixture may occur during oxidation if large amounts of water or inorganic acids are present. Preference is therefore given to using percarboxylic acids which are essentially free of water or inorganic acids. However, this oxidation can also be carried out using "technical" percarboxylic acids (eg 40% peracetic acid). In order to reduce the probability of hydrolysis, it is advantageous in this case to use buffer salts, preferably with a PH value of about 5 to 9, such as acetate buffers, carbonate buffers, phosphate buffers, etc. value 6) etc. can be added. In order to achieve as complete a conversion as possible, this oxidation is preferably carried out using an excess of percarboxylic acid. Preferably about 1 per lysylated enol group.
1.2 to 5 equivalents of percarboxylic acid are used, especially about 1.6 to 3.0 equivalents. This oxidation is carried out in an inert organic solvent, e.g.
It is advantageously carried out in ethers or chlorinated or aromatic hydrocarbons, such as diethyl ether, tetrahydrofuran, methylene chloride, toluene and the like. Ethers, especially diethyl ether, are preferred solvents. To achieve high selectivities, the oxidation is preferably carried out in dilute solutions (e.g. 0.02-0.1M solutions of the compound of formula) and the contact time with the percarboxylic acid is short (e.g. about 10-60 minutes). Hold. The pressure and temperature during this oxidation are not critical; however, the oxidation is preferably carried out at atmospheric pressure and a temperature of about -20°C to about +30°C. Hydrolysis of the compounds in the formula follows methods known per se for the hydrolysis of silyl ethers.
For example, by reaction with dilute inorganic acids, aqueous organic acids, trialkylammonium, etc., or by boiling in methanol, optionally with addition of acid (e.g. p-toluenesulfonic acid). can. The compounds of the above formula and are new,
This likewise serves as an object of the present invention. The compound with the formula is the general formula It can be produced by converting a compound of the formula, in which n and Y have the above meanings, into a silyl ether of the formula. This method is new and also forms the object of the present invention. This method is a method known per se [for example, Liebigs Ann. Chem. 1981, 1643,
Tetrahedron Letters 22 , 3455 (1981),
Synthesis 1979 , 35]. A preferred method for the silylation of a compound of formula is to react a compound of formula with a trialkylhalosilane (such as trimethylchlorosilane or trimethyliodosilane) in the presence of an alkali metal dialkylamide (such as lithium diisopropylamide). . This reaction is preferably carried out in ether (eg tetrahydrofuran). About 1.2 to 3.0 equivalents of silane and about 1.05 to 1.3 equivalents of dialkylamide, preferably about 2.0 to 2.4 equivalents of silane and about 1.2 equivalents of dialkylamide, per carbonyl and hydroxy group in the compound of formula
It is advantageous to use equivalent weights. Furthermore, in many cases it has been found to be advantageous to provide the silane and solvent and then add the dialkylamine thereto. The temperature and pressure at which this reaction is carried out are not critical. However, generally this reaction is carried out at atmospheric pressure and from about -40°C to about +30°C, preferably about -15°C.
Performed at °C. Another method particularly suitable for the silylation of compounds of the formula in which n represents the number 0 is reaction with trialkylhalosilanes (eg trimethylchlorosilane) in the presence of trialkylamines (eg triethylamine). This reaction is preferably carried out in dimethylformamide under reflux. A further preferred method is the reaction of a compound of formula with a trifluoromethanesulfonic acid trialkylsilyl ester (eg t-butyl-dimethylsilyl ester) in the presence of a trialkylamine (eg triethylamine). Methylene chloride is the preferred solvent. Pressure and temperature are not critical, and generally the reaction is carried out at atmospheric pressure and a temperature between about -40°C and room temperature, preferably between about 0 and 10°C. Free hydroxy groups that may be present in the formula are likewise silylated in this reaction, while protected hydroxy groups are not silylated. The use of ether groups therefore makes it possible to reduce the consumption of silylating agents. The introduction of the protecting group can be carried out according to methods known per se for etherification of hydroxy groups. Subsequent cleavage of the protecting group is generally not necessary since it is removed in the subsequent reaction of the compound of formula B according to Scheme 2. By the method provided by the present invention, astaxanthin is obtained in fewer steps from canthaxanthin or intermediates known in the synthesis of canthaxanthin. Equations 1 and 2, where R ¹ , R ² and R ³ have the above meanings and X represents chlorine or bromine, illustrate simple synthetic routes, and for n=0 or 1 It clearly shows the correlation of the composite layout. Compounds of formula C and compounds of formula B in which R ³ represents an ether group are novel and likewise form the object of the invention. The present invention also relates to all novel compounds, methods of preparation and uses mentioned herein. The following examples further illustrate the invention: Example 1 (a) 14 ml of tetrahydrofuran and 1.64 ml of diisopropylamine are added to a dry sulfonation flask equipped with a stirrer, thermometer, addition funnel and argon gas inlet. and cooled to -15°C in an acetone/dry ice bath. 9.5 ml of a solution of butyllithium in hexane [butyllithium content 1.90 M (18.1 mmol)] were then added dropwise to this mixture through the dropping funnel, such that the temperature was maintained at -15°C, and the mixture was stirred at this temperature for 15 minutes. did. (b) 2.83 g (5 mmol) of freshly recrystallized canthaxanthin and 3 ml (23.7 mmol) of freshly recrystallized canthaxanthin in 100 ml tetrahydrofuran and 3 ml (23.7
mmol) and cooled to -15°C to -20°C in an acetone/dry ice bath. Completely transfer the solution of lithium diisopropylamide prepared according to paragraph (a) into a gas-tight syringe and incubate at -15°C with a dosage pump.
Added to mixture within 30 minutes. After stirring for 5 minutes, the batches are rinsed with 200 ml of diethyl ether, placed in a separating funnel and in each case 200 ml of phosphate buffer solution (solution 11
Contains 6.8 g of potassium dihydrogen phosphate and 5.6 ml of 1N sodium hydroxide solution; pH value 6)
Extracted twice and then twice with 200 ml each of ice water.
In each washing operation, the amount of tetrahydrofuran dissolved in the aqueous phase was added again. The aqueous phase was backwashed with 50 ml of diethyl ether. Combine the organic phases;
Dry over sodium sulfate, filter, bath temperature 50°C
It was completely evaporated in a rotary evaporator. Thus the formula 4.1 g of crude canthaxanthin bis(trimethylsilyl)-enol ether was obtained. Example 2 (a) In a sulfonation flask equipped with a stirrer, a thermometer, a dropping funnel and an argon gas inlet,
Canthaxanthin bis(trimethylsilyl)-enol ether obtained according to Example 1 was rinsed in with 100 ml of diethyl ether [formula A']. Next, 1 g of sodium acetate and the tip of a spatula of sequestren were added, and the suspension was cooled to 15° C. using an acetone/dry ice bath. This mixture was then added to 2.9 g (16 mmol) of monoperphthalic acid in about 43 ml of diethyl ether.
(produced by diluting a monoperphthalic acid solution as described below with diethyl ether) at -15
was added dropwise from the addition funnel within 15 minutes at 0.degree. C., then the temperature was increased to 25.degree. C. and the mixture was stirred for 45 minutes. Then add the mixture to 200ml of tetrahydrofuran
The mixture was rinsed into a separatory funnel and extracted once with 50 ml of 0.5M sodium pyrosulfite solution, once with 50 ml of half-saturated sodium bicarbonate solution, and once with 50 ml of half-saturated sodium chloride solution. The aqueous phase was backwashed once with 50 ml of diethyl ether. Combine the organic phases, dry over sodium sulfate, filter and cool at bath temperature.
It was completely evaporated in a rotary evaporator at 50°C. Thus the formula 4.3 g of crude astaxanthin bis(trimethylsilyl) ether was obtained. (b) The obtained astaxanthin bis(trimethylsilyl) ether [formula A'] was transferred to a round bottom flask equipped with a reflux condenser with 80 ml of methanol and treated with a spatula tipful of p-toluenesulfonic acid, It was then heated under reflux for 30 minutes and then the methanol was completely evaporated in a rotary evaporator at a bath temperature of 50°C. The entire crude product was dissolved in methylene chloride and analyzed by high performance liquid chromatography. Thus the formula Astaxanthin shown in was obtained. The yield based on the canthaxanthin used was 67.5% astaxanthin and 2.5% adonirubine.
In addition, 5% of unreacted canthaxanthin was found. The monoperphthalic solution used above was prepared as follows: In a sulfonation flask equipped with a stirrer, thermometer, and addition funnel, 300 ml of deionized water, 2.5 g of magnesium sulfate, and 30 g of sodium hydroxide were placed. and cooled to 5°C in an ice bath. 75ml of 30% hydrogen peroxide was added dropwise to this mixture within about 2 minutes until the temperature reached 10°C.
and then a solution of 37.0 g of phthalic anhydride in 230 ml of tetrahydrofuran was added dropwise within 15 minutes at 5-10°C. After stirring for 10 minutes, reduce this batch to 20%
Pour into 600 ml of sulfuric acid and the temperature rises from 0°C to 10°C. This mixture was mixed with 250 ml each of diethyl ether.
Extracted twice. The combined ether phases were backwashed twice with 200 ml each of 40% ammonium sulfate solution (the last wash water had a pH value of 4). The two phases were backwashed with 100 ml of diethyl ether. The combined ethereal phases were dried over sodium sulphate, filtered and concentrated to a volume of approximately 40 ml on a rotary evaporator at room temperature without vacuum. The approximately 10% monoperphthalic acid solution was poured into a four-necked flask and concentrated to a volume of approximately 130 ml by bubbling under nitrogen with stirring. The resulting solution was approximately 30% (determined iodometrically). The chemical yield of monoperphthalic acid was 88% based on phthalic anhydride. Example 3 A solution of 3.5 ml of diisopropylamine in 30 ml of tetrahydrofuran in a dry sulfonation flask equipped with an addition funnel, a thermometer, a septum and an argon gas inlet was added to butyllithium in hexane at −15° C. within 5 minutes. (by syringe) with 12 ml of an approximately 2M solution of The mixture was stirred for an additional 15 minutes at -15°C. Then tetrahydrofuran 400
A solution of 5.65 g of 96% canthaxanthin in -15 ml
It was added dropwise within about 20 minutes at -20°C and the brown-purple suspension was stirred for 10 minutes. A solution of 4 ml of trimethylchlorosilane in 4 ml of tetrahydrofuran was then added dropwise to this mixture at -15 DEG C., the cooling bath was removed, and the red solution was stirred for a further 30 minutes. This mixture was added to a separatory funnel containing 200 ml of diethyl ether and phosphate buffer solution, pH 6 (as in Example 1), 200 ml of diethyl ether,
ml and shaken. The organic phase was extracted with 200 ml of phosphate buffer solution PH value 6, then water bath 200 ml.
Washed 3 times with ml and dried over sodium sulfate,
Concentrate to a volume of 100 ml on a rotary evaporator at 30°C.
This solution of canthaxanthin bis(trimethylsilyl)-enol ether was used directly in subsequent reactions. The sample was recrystallized from a diethyl ether/pentane/methanol mixture and canthaxanthin bis(trimethylsilyl)-
Enol ether [formula A′] was obtained; melting point
168-169°C; R _f value [diethyl ether/hexane, (2:1)]: canthaxanthin bis(trimethylsilyl)-enol ether about 0.75, canthaxanthin trimethylsilyl-enol ether about 0.54, canthaxanthin about 0.03. Example 4 (a) While stirring the solution of canthaxanthin bis(trimethylsilyl)-enol ether [formula A'] obtained in Example 3, sulfonation was carried out using a separating funnel, a thermometer and an argon gas inlet. In a flask, add 2 ml of sodium acetate.
g and 4 g of sodium sulfate, and-
Cooled to 15°C. A solution of 3.4 ml of about 40% peracetic acid (concentration 7.15 M according to iodometry titration) in 34 ml of diethyl ether is added dropwise to this mixture within about 5 minutes, then the cooling bath is removed and the mixture is allowed to stand for about 2 hours. Stirred. A 0.5M aqueous sodium pyrosulfite solution was added to the ice-cooled mixture in a separating funnel.
Extracted once with 100 ml, twice with 100 ml each of half-saturated aqueous sodium bicarbonate solution, and once with 100 ml of half-saturated aqueous sodium chloride solution, dried over sodium sulfate and evaporated, astaxanthin bis(trimethylsilyl) ether [formula
About 8 g of a dark red solid crude product of A' was obtained; Rf value about 0.67 [diethyl ether/hexane (2:1)]. The sample was crystallized from methylene chloride/acetone to give astaxanthin disilylether as purple platelets; melting point
196-197℃. (b) Astaxanthin bis(trimethylsilyl)
The crude product of ether [formula A'] was taken up in 20 ml of methanol and boiled under reflux for 4 hours under argon. The mixture was allowed to cool to room temperature and then to -20°C, yielding a reddish-purple precipitate of 4.5 g of crude astaxanthin.
The mother liquor was concentrated to give about 3 g of a solid red residue, which was purified on silica gel with methylene chloride/diethyl ether (9:1) as eluent.
The crude astaxanthin was chromatographed under argon pressure 0.2-0.4 bar by
0.4g was obtained. The resulting crude astaxanthin (4.9 g) was dissolved in 10 g of methylene chloride,
Argon pressure was applied to silica gel with methylene chloride/diethyl ether (9:1) as eluent.
Chromatography was performed under 0.2-0.4 bar. A homogeneous fraction was collected and recrystallized from methylene chloride/methanol, yielding 2.87 g of all-trans-astaxanthin (formula A′; purity approximately 90%); melting point 216-219°C; yield 48% based on canthaxanthin. . Example 5 565 mg of canthaxanthin in 20 ml of methylene chloride
The solution was treated with 0.56 ml of triethylamine and cooled to about 3°C in an ice bath. Then t-butyl-dimethylsilyl trifluoromethanesulfonate
Add 0.57 ml dropwise and stir this mixture for another 30 min without cooling.
Stir for a minute. The mixture was then poured into a mixture of ice and saturated sodium chloride solution and extracted with diethyl ether. The ether phase was washed three times with water, dried over sodium sulfate and concentrated. The obtained crude canthaxanthin bis(t-butyl-
The dimethylsilyl)-enol ether could be treated directly in a similar manner to Example 2 or 4 without further purification. Complete evaporation of the crude enol ether gave a dark red residue, which after recrystallization from diethyl ether/methanol gave the formula as fine purple needles in 70% yield. Canthaxanthin bis(t-butyl-
Dimethylsilyl)-enol ether was obtained; melting point 166-168°C. Example 6 96.5% 1- in 85 ml of dimethylformamide in a four-necked flask equipped with a stirrer and a reflux condenser.
(3-oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methyl-1,4
A solution of 23.1 g of -pentadien-3-ol [formula B'] was treated with 80 ml of triethylamine and 73 ml of trimethylchlorosilane. The mixture was heated at reflux (heating bath temperature 120° C.) for 2 hours with stirring and under a weak argon atmosphere. The mixture was then cooled to approximately 0° C. in an ice bath and treated with 400 ml of hexane and 200 ml of half-saturated aqueous sodium bicarbonate solution while stirring. The phases were separated and the aqueous phase was extracted with 200ml hexane. The combined organic phases were added to a saturated sodium chloride solution.
Wash once with 100 ml, dry over sodium sulfate,
Concentrate at 40°C in a rotary evaporator. The resulting brown oil (39.5 g) was distilled at 102-107°C/0.1 Torr to give trimethyl [[1-methyl-3-
[2,6,6-trimethyl-3-(trimethylsiloxy)-1,3-cyclohexadien-1-yl]
-1-vinylallyl]oxo]silane [formula B']
Obtained 35.0g; purity approximately 77%. Example 7 Approximately 40% peracetic acid 18.3g, anhydrous methylene chloride 190ml,
3.8 g of anhydrous magnesium sulfate and 2.2 g of anhydrous sodium acetate were placed in a four-necked flask equipped with a stirrer under argon and cooled to -15° C. with stirring. This suspension was mixed with 77% trimethyl [[1-methyl-3-[2,6,6-trimethyl-3-(trimethylsiloxy)-1,3-cyclohexadien-1-yl]-1] in 70 ml of methylene chloride. A solution of 35 g of -vinylallyl]oxo]silane (formula B'; prepared according to Example 6) was added dropwise within 10 minutes. Remove the ice bath and stir the mixture for a further 15 minutes until the temperature reaches 17
The temperature rose to ℃. The mixture was treated with stirring with 38 g of anhydrous sodium carbonate and 38 g of sodium bicarbonate, stirred for a further 20 minutes and filtered (rinsed with 150 ml of methylene chloride). Trimethyl [[1
-Methyl-3-[2,6,6-trimethyl-3-
A solution (approximately 400 ml) containing oxo-4-(trimethylsiloxy)-1-cyclohexen-1-yl]-1-vinylallyl]oxy]silane [formula B'] was treated directly. The resulting filtrate was treated with 40 ml of triethylammonium fluoride with vigorous stirring at room temperature and then stirred for a further 20 hours. This solution was washed successively with 100 ml of half-saturated sodium chloride solution, 100 ml of half-saturated sodium pyrosulfite solution and 100 ml of half-saturated sodium chloride solution, dried over sodium sulfate and concentrated in a rotary evaporator at 40°C (bath temperature). . Thus, 1-(4-hydroxy-3
25.3 g of -oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methyl-1,4-pentadien-3-ol [formula B'] were obtained; purity by gas chromatography. 79.8
%. The obtained 1-(4-hydroxy-3-oxo-
2,6,6-trimethyl-1-cyclohexene-
1-yl)-3-methyl-1,4-pentadien-3-ol [formula B'] is converted to the bromide with 30 ml of a 63% hydrogen bromide solution in 250 ml of methylene chloride, and this bromide is then converted to triphenyl Converted to phosphonium bromide with 26.2 g of phosphine. Thus, the crude [(4E)-5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1
-cyclohexen-1-yl)-3-methyl-2,
45.3 g of 4-pentadienyl]-triphenylphosphonium bromide [formula'] was obtained; melting point
157-163℃. 32.4 g of 89.9% trans product after recrystallization from ethyl acetate/methylene chloride 2:1 at 0°C
was obtained; melting point 181-182°C. After two further recrystallizations from ethyl acetate/methylene chloride, the purity was 96%; mp 186-187°C. Example 8 In a four-necked flask equipped with a stirrer, 22.2 g of diisopropylamine was added to anhydrous tetrahydrofuran.
Dissolved in 330ml and cooled to -15°C under argon.
Add to this solution, with stirring, 106 ml of an approximately 2M solution of butyllithium in hexane and, after 10 minutes, 97% 1-(3-oxo-
2,6,6-trimethyl-1-cyclohexene-
A solution of 23.2 g of 1-yl)-3-methyl-1,4-pentadien-3-ol [formula B above] was added dropwise. Then add 48ml of trimethylchlorosilane to this.
was added dropwise so that the temperature could be maintained at -15°C. The mixture became homogeneous again. After the addition, the cooling bath was removed and the mixture was allowed to warm to room temperature. The mixture was transferred into a 2 volume flask (rinsing with pentane) and the solvent was removed on a rotary evaporator at approximately 40° C. (bath temperature) under vacuum. The residue was taken up in approximately 250 ml of pentane, the resulting suspension was filtered, and the excess residue was rinsed several times with pentane (250 ml total). The liquid was evaporated in a rotary evaporator to give the crude product (43.3
g) was distilled at 110°C/0.01 Torr. Thus, as a pale yellowish oil with a purity of 98%, trimethyl
-Methyl-3-[2,6,6-trimethyl-3-
(trimethylsiloxy)-1,3-cyclohexadien-1-yl]-1-vinylallyl]oxy]
37.2 g of silane [formula B' above] was obtained. Example 9 (a) Trimethyl [[1-methyl-3-[2,6,6
-Trimethyl-3-(trimethylsiloxy)-
1,3-cyclohexadien-1-yl]-1
-vinylallyl]oxy]silane (the above formula
B′; purity 98%) 37.2g with anhydrous diethyl ether
250 ml and treated with 24.7 g of sodium bicarbonate, 31.2 g of sodium carbonate and 24.7 g of sodium acetate under argon and with good stirring. The mixture was stirred for ten minutes at -5°C and then dissolved in monoperphthalic acid in diethyl ether.
Treated within 20 minutes with 326 ml of 0.9N solution. Pour the mixture into 100ml of saturated sodium bicarbonate solution,
Extracted with a mixture of 500 ml water and 500 ml diethyl ether. The organic phase was mixed once with 200 ml of half-saturated sodium pyrosulphite solution and 100 ml each with sodium chloride solution.
Washed twice with ml and evaporated. Trimethyl [[1-methyl-3-[2,6,6-trimethyl-3-oxo-4-(trimethylsiloxy)-
The evaporation residue (41.2 g) of 1-cyclohexen-1-yl]-1-vinylallyl]oxy]silane [formula B' above] was used directly for the treatment. (b) Dissolve this evaporation residue in 200 ml of methylene chloride,
Then triethylammonium fluoride solution
40 ml and stirred at room temperature for 4 hours. The mixture was poured into 100 ml of half-saturated sodium bicarbonate solution, then the organic phase was separated and evaporated. Thus, as an oil, 1-(4-hydroxy-
3-oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methyl-1,
4-Pentadien-3-ol [Formula B' above]
28.0 g of evaporation residue was obtained, which was processed directly. (c) The oil obtained was taken up in 250 ml of anhydrous methylene chloride at 0° C. under argon and treated within 10 minutes with 30 ml of 63% hydrogen bromide solution. This mixture was taken up in approximately 0.5 ml of ethyl acetate, washed once with saturated sodium chloride solution and once with saturated sodium bicarbonate solution, dried over sodium sulfate, and dried at 30 °C.
(bath temperature) in a rotary evaporator to approximately 300 ml. The bromide solution thus obtained was diluted with triphenylphosphine in 100 ml of anhydrous ethyl acetate.
It was added dropwise to 26.2 g of solution and stirred overnight at room temperature.
After filtration, crude [5-(4-hydroxy-2,
6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-
pentadienyl]-triphenylphosphonium bromide (formula '; content as determined by high performance liquid chromatography: 2E-isomer 77.2% and
49.0 g of 2Z-isomer (12.1%) was obtained; melting point
162-164℃. Recrystallized from 200 ml of methylene chloride and 400 ml of ethyl acetate to give phosphonium salt (content: 84.5% of 2E-isomer and 10% of 2Z-isomer).
Obtained 43.2g; melting point 178-180°C. Example 10 1-(3-oxo-2,6,6-trimethyl-
1-cyclohexen-1-yl)-3-methyl-
1,4-pentadien-3-ol [Formula B]
2.34g in 5ml hexane and 5ml diethyl ether
2 drops of tricaprylmethylammonium chloride and an aqueous solution of potassium hydroxide (prepared from 70 g of powdered potassium hydroxide and 50 ml of water) 4.54
ml and stirred well. Next, 1.98 g of sulfuric acid was added to this mixture, and the reaction process was monitored by gas chromatography. After stirring for 4 hours at room temperature (product/extract ratio 99.7:0.3), the mixture was poured onto ice. The organic phase was separated, washed neutral with water, dried over sodium sulfate and concentrated under water pump vacuum. 1-(3-oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methoxy-3-methyl- as a yellow oil.
2.47 g of 1,4-pentadiene [formula C'] was obtained. A solution of 19.5 g of diisopropylamine in 300 ml of anhydrous tetrahydrofuran was cooled to -20°C, treated dropwise with 126 ml of a 1.6M solution of butyllithium in hexane and stirred for a further 20 minutes at -20°C. The mixture was then dissolved in 50 ml of anhydrous tetrahydrofuran.
The mixture obtained by dropwise treatment with a solution of 40.0 g of oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methoxy-3-methyl-1,4-pentadiene [formula C'] The mixture was further stirred at 0°C for 1 hour. After cooling to -20°C and rapid addition of 21 g of trimethylchlorosilane, the mixture was stirred at 0°C for 15 min (at this point 96.5% of the extract had been converted to the desired product according to gas chromatography). ). The mixture was treated dropwise with 80 ml of saturated sodium chloride solution and then extracted with diethyl ether. The organic phase was washed three times with saturated sodium chloride solution, dried over sodium sulfate and concentrated under water pump vacuum. 1-[2,6,
6-trimethyl-3-(trimethylsiloxy)-
1,3-cyclohexadien-1-yl]-3-
51.0 g of methoxy-3-methyl-1,4-pentadiene (formula B″; purity 96.36%) was obtained. Example 11 1-[2,6,6-trimethyl-3-(trimethylsiloxy)-1,3-cyclohexadiene-1
-yl]-3-methoxy-3-methyl-1,4-
A mixture of 32.0 g of pentadiene [formula B''], 10.0 g of sodium hydrogen carbonate, 10.0 g of magnesium sulfate trihydrate, and 500 ml of diethyl ether was thoroughly stirred at 2 to 5°C, and then 26.45 g of 40% peracetic acid was added dropwise. treated and allowed to warm to room temperature.Then the mixture was
The mixture was cooled to 0.degree. C., treated dropwise with 90 ml of a mixture of methanol and 1N hydrochloric acid (volume ratio 1:1), and extracted with diethyl ether. The organic phase was washed twice with cold half-strength sodium pyrosulfite solution, once with ice water, and twice with ice water containing a small amount of saturated sodium bicarbonate solution.
Then, it was further washed twice with ice water. After drying over sodium sulfate and concentration at 35°C under water pump vacuum, the crude 1-(4-hydroxy-3-oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)- 3-methoxy-3-methyl-1,
4-pentadiene (formula B″; purity 91.5%) 26.4g
is obtained, which is still 1-(3-oxo-2,
6,6-trimethyl-1-cyclohexene-1-
yl)-3-methoxy-3-methyl-1,4-pentadiene (7.07%). 91.55% crude 1-(4) in 400 ml methylene chloride
-hydroxy-3-oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methoxy-3-methyl-1,4-pentadiene [formula
58.0 g of solution was stirred at -20°C, 38.5 g of 63% hydrogen bromide solution was rapidly added dropwise, and then stirred for an additional 10 minutes at -15°C. The mixture was extracted with cold ethyl acetate. The extract was washed with a cold 25% aqueous sodium bromide solution and a small amount of saturated sodium bicarbonate solution and then incubated under water pump vacuum at room temperature for approximately 70 min.
Concentrated to a volume of ~80ml. The resulting solution was added to a solution of 52.4 g of triphenylphosphine in 200 ml of ethyl acetate and the mixture was stirred at room temperature for about 3-4 hours. After crystallizing the product, the mixture was heated to 5°C.
The mixture was stirred for a further 15 hours at 30° C., then filtered with suction and the filtrate was dried at 35° C. under water pump vacuum.
The resulting crude phosphonium salt (95.3 g) was recrystallized from 200 ml of methylene chloride and 400 ml of ethyl acetate. Thus, [(4E)-5-(4-hydroxy-
2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-
pentadienyl]-triphenylphosphonium bromide (formula ′; 2E-isomer 83.36% and 2Z-
80.35 g (containing 13.55% isomer) was obtained; melting point
179-182℃.

Claims (1)

[Claims] 1. General formula In the formula, n represents the number 0 and X represents the group [Formula], or n represents the number 1 and X represents the number 6,11-dimethylhexadeca-2,4,6,8,10,12, represents a 14-heptaene-2,15-diyl group, the symbol R ¹ has the same or different meaning and represents an alkyl group, and the symbol R ² represents a trialkylsiloxy group -OSi(R ¹ ) ₃ or an ether A compound representing a group. 2 General formula In the formula, n represents the number 0 and X represents the group [Formula], or n represents the number 1 and X represents the number 6,11-dimethylhexadeca-2,4,6,8,10,12, 14-heptaene-2,15-diyl group, the symbol R ¹ has the same or different meaning and represents an alkyl group, and the symbol R ² represents a trialkylsilyloxy group -OSi(R ¹ ) ₃ or A general formula characterized by oxidizing the silyl-enol ether of , which represents an ether group, with a percarboxylic acid A method for producing a compound of the formula, wherein n, X and R ¹ have the above meanings. 3 General formula as starting material 2. A method according to claim 2 using a compound of the following formula, wherein the symbol R ¹ has the meaning as defined in claim 2. 4 General formula as starting material 2. The method according to claim 2, using a compound of the following, wherein the symbols R ¹ and R ² have the meanings defined in claim 2. 5. Process according to claim 4, in which as starting material a compound of the formula B is used, in which R ² represents an alkoxy group containing 1 to 5 carbon atoms, preferably methoxy. 6 General formula as starting material 4. The method according to claim 4, using a compound of the following, wherein the symbol R ¹ has the meaning as defined in claim 2. 7. Process according to any one of claims 2 to 6, in which as starting material a compound of the formula R ¹ represents an alkyl group containing 1 to 5 carbon atoms. 8 As a starting material, trialkylsiloxy group -
8. A method according to claim 7 using a compound of the formula in which OSi( ^R1 ) ₃ is trimethylsiloxy or t-butyl-dimethylsiloxy. 9. The method according to any one of claims 2 to 8, wherein the oxidation of the compound of formula 9 is carried out using monoperphthalic acid, peracetic acid or perbenzoic acid.