JPH0472835B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is to process a compound represented by the following general formula () to obtain a compound represented by the following general formula ().
The present invention relates to a method for producing 8α,12-epoxy-13,14,15,16-tetranordan. The chemical formula () is dodecahydro-3a,6,6,9a-tetramethylnaphtho[2.1-b]furan according to the nomenclature of Chemical Abstracts, and is also commonly called ambrox. Compound () is a substance useful as a fragrance with an excellent amber aroma. Compound (), namely Ambrox, is manufactured using manur and scleraol as raw materials, but these are both compounds obtained by extraction from New Zealand coniferous trees, and are produced in small quantities and are expensive. The purpose of the present invention is to provide a method for producing an amber-scented compound () from raw pine tar that can be produced in large quantities and is inexpensive.More precisely, the following compound () (compound (a) ,same(
The object of the present invention is to provide a method for producing a compound () from (b) (including b), and is not limited to raw pine resin. Raw pine tar contains various compounds, the main component of which is levopimaric acid (compound (a) below). Its content ranges from about 15% to 50%, for example, Organic Synthesis (Organic Synthesis).
Syntesis, Collective Volume V, p. 699). When compound (a) is reacted with diazomethane, methyl levopimarate (the following compound (b) is obtained. When compound (b) is oxidized, compound (a) is obtained. As an oxidation method, for example,
A combination of ozone oxidation and Jones oxidation is used. In this case, for ozone oxidation, ethyl acetate or a methylene chloride-methyl alcohol mixture is used as a solvent, and ozonide is generated with an ozone-containing gas at 5°C or lower, especially -70°C, and the ozonide is converted into potassium iodide or dimethyl Decomposed by sulfides. The above-mentioned compound (a) is contained in the product of this ozone oxidation, but by further subjecting the product to Zion's oxidation, that is, dissolving the product in acetone and using Zion's reagent (chromic acid-sulfuric acid aqueous solution). ) can be added at -10°C to 20°C and reacted to increase the yield of compound (a). From the Johns oxidized product,
If compound (a) is extracted as a saponified product and then reacted with diazomethane to convert it into compound (b), purification by silica gel column chromatography becomes easy. When compound (b) is subjected to a Wittig reaction, compound (b) is obtained. Wittig reagents used in the Wittig reaction to synthesize alkenes from carbonyl compounds include methyltriphenylphosphonium bromide, methyltriphenylphosphonium iodide, methyltriphenylphosphonium chloride, etc. as the phosphonium salt, and potassium as the base. Tert-butoxide, potassium tert-amyloxide, etc. are further synthesized using isopropyl ether, toluene, benzene, etc. as a solvent. The reaction temperature and reaction time of Wittig reaction are room temperature to 110℃, respectively.
And about 1 to 6 hours is appropriate. Compound (b) is mixed with a solvent such as chloroform, methylene chloride, and a peracid, preferably m-chloroperbenzoic acid, perbenzoic acid, peracetic acid, perphthalic acid, etc., at about 15 to 80°C for about 30 minutes. After reacting for ~48 hours, epoxidation of the double bond occurs to yield compound (). Compound () is reduced from about 0 to 60% using a reducing agent, e.g., lithium aluminum hydride, in a solvent, e.g., tetrahydrofuran, ethyl ether, etc.
℃ for about 0.5 to 12 hours to obtain compound (). Compound (a) is obtained by dissolving compound () in a basic solvent such as pyridine and reacting it with methanesulfonyl chloride, at a reaction temperature of 0.
-50°C and reaction time is preferably 6 to 48 hours. Compound (b) can also be obtained by reacting compound () with P-toluenesulfonyl chloride under the same conditions as above. Alternatively, compound (c) can be obtained by dissolving compound () in a solvent such as toluene or benzene, adding dimethyl sulfoxide and chlorotrimethylsilane, and reacting at 15 to 110°C for 10 minutes to 24 hours. When compound (c) is dissolved in a basic solvent such as pyridine and reacted with methanesulfonyl chloride, compound (a) is obtained, and similarly, compound (a) is obtained.
Reaction of c) with P-toluenesulfonic acid yields compound (b). Conversely, compound (a)
Alternatively, compound (c) can be obtained by hydrolyzing compound (b) under acidic or basic conditions. There is also the following alternative method for obtaining compound () or (c) from compound (b). That is,
When compound (b) is dissolved in alkaline methyl alcohol and treated at 20-70°C for 1-24 hours, it is partially hydrolyzed to yield compound (a). Compound (a) is obtained by dissolving compound (a) in a solvent such as acetic acid, tetrahydrofuran, methyl alcohol, etc. and reacting it with a mineral acid such as sulfuric acid, hydrochloric acid, etc. Compound () is reduced from about 0 to 60% using a reducing agent, e.g., lithium aluminum hydride, in a solvent, e.g., tetrahydrofuran, ethyl ether, etc.
℃ for about 0.5 to 12 hours to obtain compound (). Compound (b) can also be obtained by reducing compound () with a reducing agent such as diborane in a solvent such as tetrahydrofuran. Compound (c) is obtained by reducing compound (b) using a reducing agent such as lithium aluminum hydride. Compound () is obtained by treating compound (a) or (b) with a reducing agent. As the reducing agent, for example, sodium iodide-zinc powder is used, and in this case, N,N-dimethylformamide,
Among hexamethyltriamide phosphate, etc., 80~
It is appropriate to react at 140°C for 1 to 12 hours. Compound (e) is obtained by oxidizing compound (c). The oxidizing agent at this time is, for example, pyridinium chlorochromate or chromic acid.
A reaction is carried out using a pyridine complex at 0 to 30°C for 0.5 to 5 hours. Compound (e) is subjected to Wolff-Kissiner reduction to obtain compound (). That is, the compound (
When the aldehyde group in e) is replaced with hydrazone or semicarbazone and heated in the presence of a strong base such as an alkali metal alkoxide, compound () is obtained. Compound () can also be obtained by reacting compound (e) with ethanedithiol using an acid catalyst to form a thioketal into compound (f), and further desulfurizing and reducing it using a reducing agent such as Raney nickel. be able to. Here, compounds (), compound (a), compound (
b); Compound (), (a), (b); Compound (), (a), (b); Compound ();
Compound (); Compound (), Compound (a), Compound (
b), (c), (d), (e), (
f); Compound (); The chemical formulas of Compound () are collectively shown. However, R ₁ is CO ₂ H or CO ₂ CH ₃ group, R ₂ is any one of CHO, CO ₂ H and CO ₂ CH ₃ group, and R ₃ is CO ₂ H, CO ₂ CH ₃ , CH _2OH ,
CH ₂ OSO ₂ CH ₃ , CH ₂ OSO ₂ C ₆ H ₄ CH ₃ , CHO,

[Formula] represents any one group selected from the groups. When R ₁ is CO ₂ H; Compound (a) When R ¹ is CO ₂ CH ₃ ; Compound (b) When R ₁ is CO ₂ CH ₃ and R ₂ is CO ₂ H; the compound (
a) When R ₁ is CO ₂ CH ₃ and R ₂ is CO ₂ CH ₃ ; Compound (b) When R ₁ is CO ₂ CH ₃ and R ₂ is CO ₂ H; the compound (
a) When R ₁ is CO ₂ CH ₃ and R ₂ is CO ₂ CHH ₃ ; Compound (b) When R ₃ is CH ₂ OSO ₂ CH ₃ : Compound (a) When R ₃ is CH ₂ OSO ₂ C ₆ H ₄ CH ₃ : Compound (
b) When R ₃ is CH ₂ OH: Compound (c) When R ₃ is CO ₂ CH ₃ : Compound (d) When R ₃ is CHO: Compound (e ₎

[Formula]: Compound (f) Next, examples of the present invention will be described, but the present invention is not limited thereto. Example (1) Production of compound (b) from compound (b) Methyl levopimarate (2.5 g of compound (b) was dissolved in 20 ml of methylene chloride, and dissolved in 10 ml of methyl alcohol.
Added ml. Ozone-oxygen mixed gas was blown into the solution for 1 hour while the solution was cooled to -70°C using a Draer ice-acetone cryogen. Next, nitrogen gas was blown in to remove excess ozone, and then 2.5 ml of dimethyl sulfide was added and the temperature was returned to room temperature. After concentrating the reaction solution under reduced pressure, it was dissolved in 50 ml of acetone, and 5 ml of Jones's reagent (13.3 g of chromic acid dissolved in 12 ml of sulfuric acid and 25 ml of water) was added dropwise under ice cooling, followed by stirring for 1 hour under ice cooling. . After adding 2 ml of isopropyl alcohol to decompose the excess oxidizing agent, 200 ml of water and 200 ml of ethyl ether were added to perform ether extraction. 200 ml of 2N potassium hydroxide solution was added to the ether layer, and the saponified product was extracted into the aqueous layer. Hydrochloric acid was added to the aqueous layer to make it acidic, ethyl ether was added, and the saponified product was extracted into the ether layer. This ether layer was washed with a saturated aqueous sodium chloride solution and dehydrated with anhydrous sodium sulfate, and then an ethyl ether solution of diazomethane was added to convert the carboxylic acid into a methyl ester. The reaction solution was concentrated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (hexane: ethyl acetate 5:1) to obtain 1.2 g of compound (b). Compound (b): Pale yellow oil C ₁₇ H ₂₆ O ₅ (molecular weight 310) Yield 48.9% (counter compound (b)) IR: 1730 cm ^-1 (-CO ₂ Me) ¹³ C-NMR: 209.6 ppm (C -8, C=0),
178.4ppm (C-18, -CO2-) 173.4ppm (C-12, _-CO2- ) 52.1ppm (-
OCH ₃ ) 51.7 ppm (-OCH ₃ ) (2) Compound (b) to compound (a) 7.8 g of methyltriphenylphosphonium iodide
and 2.1 g of potassium tert-butoxide were dispersed in 70 ml of isopropyl ether under a nitrogen stream and heated at 60°C.
The mixture was stirred for 30 minutes. 2.8g of compound (b) there
A 20 ml solution of isopropyl ether was added thereto, and the mixture was refluxed for 2 hours. After cooling, 50 ml of water was added and stirred for 30 minutes. The organic layer was separated, washed with saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. Furthermore, the residue concentrated under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate 8:1) to obtain 1.65 g of compound (b). Compound (b) White crystals Melting point 65-68℃
C ₁₈ H ₂₈ O ₄ (molecular weight 308) Yield 59.3% (counter compound (b)) IR: 1730 cm ^-1 (-CO ₂ Me) ¹³ C-NMR: 179.0 ppm (C-18, -CO ₂ -)
174.2ppm (C-12, -CO ₂ -) 51.9ppm (-OCH ₃ ) 51.6ppm (-OCH ₃ ) 107.0ppm (C-17, =CH ₂ ) 148.4ppm (C-
8, C=) (3) Production of compound (a) from compound (b) Dissolve 1.45 g of compound (b) in 100 ml of chloroform, add 1.0 g of m-chloroperbenzoic acid, dissolve, and leave at room temperature for 18 hours. I left it still. The reaction solution was washed with an aqueous sodium iodide solution, an aqueous sodium thiosulfate solution, an aqueous sodium bicarbonate solution, and a saturated aqueous sodium chloride solution in this order, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude compound ().
1.54g was obtained. Under nitrogen flow, lithium aluminum hydride 0.5
g was dispersed in 50 ml of tetrahydrofuran, and a solution of 1.54 g of the crude compound (2) in 20 ml of tetrahydrofuran was added dropwise, followed by refluxing for 2 hours. After cooling, a saturated aqueous sodium sulfate solution was added to remove a white precipitate. The liquid was concentrated under reduced pressure to obtain 1.2 g of crude compound (). Dissolve 1.2 g of the crude compound () in 100 ml of pyridine, and add 2.0 ml of methanesulfonyl chloride under ice cooling.
was added and then allowed to stand at room temperature for 24 hours. Ether extraction was performed by adding 200 ml of ethyl ether and 200 ml of water to the reaction solution. The ether layer was washed with dilute hydrochloric acid and a saturated aqueous sodium chloride solution, then dehydrated with anhydrous sodium sulfate, and further concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (hexane: ethyl acetate 3:1) to obtain the compound (
a) Obtained 0.55g. Compound (a) White crystals Melting point 109-110℃
C ₁₇ H ₃₀ O ₄ S (molecular weight 330) Yield 35.4% (counter compound (b)) IR: 1340 cm ^-1 1180 cm ^-1 (-OSO ₂ CH ₃ ) ¹³ C-NMR: 79.4 ppm ((-8,

[Formula]) 77.6ppm (C-18, -CH ₂ -O-SO ₂ 64.8ppm (C-12, -CT ₂ -O-) 37.1ppm (-
OSO ₂ CH ₃ ) (4) Synthesis of compound () from compound (a) Dissolve 3.2 g of compound (a) in 50 ml of N,N-dimethylformamide, add 3.2 g of zinc dust (activated by acid washing) and iodine. 5.0 g of sodium chloride was added, heated to 115°C, and stirred for 6 hours. After cooling, 100 ml of ethyl acetate was added and filtered.
The solution was washed with an aqueous sodium thiosulfate solution and a saturated aqueous sodium chloride solution, then dehydrated with anhydrous sodium sulfate, and further concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (hexane: ethyl acetate 20:1) to obtain compound (). i.e.
1.2 g of 8α,12-epoxy-13,14,15,16-tetranorhabdane and 1.0 g of compound (a) were obtained. Compound () White crystals Melting point 73-74℃
C ₁₆ H ₂₈ O (molecular weight 236) Yield 52.4% (counter compound (a) IR1010cm ^{-1 13} C-NMR79.7ppm (C-8,

[Formula]) 64.8ppm (C-12, -CH ₂ -O-) 33.6ppm (C-18, -CH ₃ )

Claims (1)

[Claims] 1. A compound represented by the following general formula [] is treated with an oxidizing agent to obtain a compound represented by the following general formula [], which is subjected to a Wittig reaction to obtain a compound represented by the following general formula []. The compound is then treated with an oxidizing agent, a reducing agent, and a dehydrating agent in that order, or a mineral acid, a reducing agent, and a dehydrating agent are treated in that order to form a compound represented by the following general formula [], which is further treated with a reducing agent. 8α, 12-Epoxy-13, 14,
Method for producing 15,16-tetranorabdane. _{R1 is CO2H} or _CO2CH3 R ₁ is CO ₂ H or CO ₂ CH ₃ R ₂ is CHO, CO ₂ H or CO ₂ CH ₃ R ₁ is CO ₂ H or CO ₂ CH ₃ R ₂ is CHO, CO ₂ H or CO ₂ CH _{3 R3 is CO2H , CO2CH3 , CH2OH , CH2OSO2CH3 or CH2OSO2C6H4CH3 _ _}