JPH0472834B2 - - 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 8β,12-epoxy-13,14,15,16,17-pentanollabdane. The compound formula () is dodecahydro-6,6,9a-trimethylnaphtho[2,1b]furan according to the nomenclature of Chemical Abstracts. Compound () is useful as a perfume with an excellent amber aroma. As a fragrance with an amber scent, a compound called ambrox is manufactured using manur and scleraol as raw materials, but these are both compounds obtained by extraction from coniferous trees grown in New Zealand, and production quantities are small. It's expensive. The purpose of the present invention is to provide a method for producing a compound () with an amber scent from raw pine tar, which is produced in large quantities and is inexpensive.More precisely, the following compound () (compound (a) ,same(
b). ), and is not limited to raw pine tar. 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).
Synthesis, Collective Volume V, p. 699). Compound (a)
When reacted with diazomethane, methyl levopimarate (compound (b) below) is obtained. Oxidation of compound (b) yields compound (a). As the 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 sulfate. Decomposes due to fluid. 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). )
The yield of compound (a) can be increased by adding and reacting at -10°C to 20°C. After extracting compound (a) as a saponified product from the product of Johns oxidation, reacting it with diazomethane,
If compound (b) is used, purification by silica gel column chromatography becomes easy. Compound (b) is heated at about 0 to 60°C using a reducing agent such as lithium aluminum hydride in a solvent such as tetrahydrofuran, ethyl ether, etc.
Compound () is obtained by reacting for about 0.5-12 hours. 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. When compound (a) or (b) is treated with a reducing agent, compound () is obtained. As the reducing agent, for example, sodium iodide-zinc powder is used, and in this case, 80
It is appropriate to react at ~140°C for 1 to 12 hours. There is also the following alternative method for obtaining compound () from compound (a) or (b). That is, when these are hydrolyzed under acidic conditions or basic conditions, compound (c) is obtained, and when this is oxidized using an oxidizing agent, compound (d) is obtained. For example, using pyridinium chlorochromate or chromic acid-pyridine complex, the reaction is carried out at 0 to 30°C for 0.5 to 5 hours. Compound (d) is subjected to Wolff-Kissiner reduction to obtain compound (). That is, when the aldehyde group of compound (d) is converted to 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 (d) with ethanedithiol using an acid catalyst to form a thioketal into compound (e), and further desulfurizing and reducing it using a reducing agent such as Raney nickel. be able to. Further, there is the following alternative method for obtaining compound (c), compound (a), or compound (b) from compound (b). That is, when compound (b) is reduced using sodium borohydride under basic conditions, compound () is obtained. When this is reduced using diborane, compound (f) is obtained. Compound (c) is obtained by reducing compound (f) using lithium aluminum hydride. When this product is dissolved in a basic solvent such as pyridine and reacted with methanesulfonyl chloride, compound (a) is obtained, and similarly, compound (c) is obtained.
Compound (b) is obtained by reacting P-toluenesulfonyl chloride with P-toluenesulfonyl chloride. Alternatively, dissolve compound (b) in a solvent such as toluene or benzene, add dimethyl sulfoxide and chlorotrimethylsilane, and heat the mixture at 15 to 110°C for 10 minutes.
Compound (c) can also be obtained by reacting for 24 hours.
is obtained. Compound (c), (a), or (b) thus obtained can be converted into compound () by the method described above. Here, compounds (), compound (a), compound (
b); Compound (), Compound (a), Compound (b); Compound (); Compound (), Compound (a), Compound (b),
Same (c), Same (d), Same (e), Same (f);
Compound (): The chemical formula of compound () is shown collectively. 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 group. , _CH2OH ,
CH ₂ OSO ₂ CH ₃ ,

[Formula] CH ₃ OSO ₂ C ₆ CH ₄ CH Indicates one group selected from ₃ groups. When R ₁ is CO ₂ H, compound (a), R ¹ is
For 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 _R3 is _CH2OSO2CH2 , _{compound (} a);
If R ₃ is CH ₂ OSO ₂ C ₆ H ₄ CH ₃ then the compound (
b); When R ₃ is CH ₂ OH, compound (c); When R ₃ is
In the case of CHO, compound (d); R ₃ is

In the case of [Formula], compound (e); If R ₃ is CO ₂ CH ₃ , 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 10 g of methyl alcohol was dissolved in 20 ml of methylene chloride.
Added ml. Ozone-oxygen mixed gas was blown into the solution for 1 hour while cooling the solution to -70°C using a dry 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 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. After the dropwise addition, the mixture was stirred for 1 hour under ice cooling. did. After adding 2 ml of isopropyl alcohol to decompose excess oxidizing agent, ether extraction was performed by adding 200 ml of water and 200 ml of ethyl ether. 200 ml of 2N aqueous potassium hydroxide solution was added to the ether layer, and the saponified product was extracted into the aqueous layer. The aqueous layer from which the saponified products were extracted was made acidic by adding hydrochloric acid, ethyl ether was added, and the saponified products were extracted into the ether layer. This ether layer was washed with a saturated aqueous sodium salt solution and dehydrated with anhydrous sodium sulfate, and then an ethyl ether solution of diazomethane was added to convert the carboxylic acid into methyl ester. The reaction solution was concentrated under reduced pressure, and the resulting residue was subjected to column chromatography (hexane: ethyl acetate 5:1) using silica gel to obtain the compound (
b) Obtained 1.2g. Compound (b): pale yellow oil C ₁₇ H ₂₆ O ₅ (molecular weight 310) yield 48.9% (compared to compound (b)),
IR: 1730 cm ^-1 ; ¹³ C-NMR: 209.6 ppm (C-
8, = 0), 178.4ppm (C-18, -COO-),
173.4ppm (C-12, -COO-), 52.1ppm (-
OCH ₃ ), 51.7 ppm (-OCH ₃ ) (2) Compound (b) → Compound (a) In a nitrogen gas atmosphere, add 2.7 g of lithium aluminum hydride to a suspension of 200 ml of tetrahydrofuran,
A solution of 7.0 g of compound (b) in 30 ml of tetrahydrofuran was added dropwise with stirring at room temperature, followed by refluxing for 1 hour. After cooling, a saturated aqueous sodium sulfate solution was added, and the white precipitate was filtered off. The filtrate was concentrated under reduced pressure to obtain a crude compound (). This was dissolved in 200 ml of pyridine, and 5.0 ml of methanesulfonyl chloride was added under ice-cooling, followed by standing at room temperature for 2 days. Add 500ml of ether and 500ml of water to this solution,
Ether extraction was performed. The ether layer was washed with dilute hydrochloric acid and saturated aqueous sodium chloride, and then dehydrated with anhydrous sodium sulfate. The residue obtained by further concentration under reduced pressure was subjected to silica gel column chromatography (hexane: ethyl acetate 3:1) to obtain 1.8 g of compound (a). Compound (a): pale yellow oil, C ₁₆ H ₂₈ O ₄ S (molecular weight 316), yield 25.2% (compared to compound (b)) IR: 1350 cm ^-1 , 1175 cm ^-1 , (-
OSO ₂ CH ₃ ) ¹³ CNMR77.7ppm (C-18, -CH ₂
-OSO ₂ -), 77.3ppm (C-8, CH-O
-), 66.2ppm (C-12, -CH2 _- O-),
37.0ppm (-OSO ₂ CH ₃ ) (3) Compound (a) → Compound () Dissolve 6.0 g of compound (a) in 50 ml of N,N-dimethylformamide, and add 6.0 g of zinc powder (activated by acid washing). and 11 g of sodium iodide were added, heated to 115°C, and stirred for 6 hours. After cooling, 100 ml of ethyl acetate was added and filtered. The filtrate was washed with an aqueous sodium thiosulfate solution and a saturated aqueous sodium chloride solution, and then dehydrated with anhydrous sodium sulfate.
The residue obtained by further concentration under reduced pressure was subjected to silica gel chromatography (hexane: ethyl acetate 20:
1) to obtain 2.2 g of compound (), namely 8β,12-epoxy-13,14,15,16,17-pentanollabdane, and 2.4 g of compound (a). Compound (): colorless crystals, melting point 54°C to 55°C, C ₁₅ H ₂₆ O (molecular weight 222), yield 52.2% (compared to compound (a)), IR: 1040 cm ^{-1 13} CNMR 77.8 ppm (C-8, CHO), 66.4ppm
(C-12, -CH ₂ O-), 33.8ppm (C-18, -
_CH3 ), 22.2ppm (C-19, _-CH3 ), 15.5ppm
(C-20, _-CH3 )

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 then treated with a reducing agent and a dehydrating agent to obtain the following general formula (). A compound represented by formula (),
8β,12-epoxy represented by the following general formula (), which is further treated with a reducing agent or an oxidizing agent and a reducing agent after hydrolysis.
13, 14, 15, 16, 17 - Method for producing pentanollabdan. (R ₁ in the formula is −CO ₂ H or −CO ₂ CH ₃ ; R ₂ is −CHO, −CO ₂ H or −CO ₂ CH ₃ ; R ₃ is −
_{Represents CO2H , -CO2CH3 , -CH2OH , -CH2OSO2CH3 or -CH2OSO2C6H4CH3 . _} )