JPH0245614B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel cispentene derivative and a method for producing the same. More specifically, the present invention relates to the general formula () (In the formula, X represents a bromine or chlorine atom, and R ¹
represents an acetyl group, a propionyl group, a butyryl group, or a benzyl group) and a method for producing the same. The cispentene derivatives represented by the general formula () provided by the present invention are useful for synthesizing β-santalol, which is the main component of sandalwood oil, which is indispensable for its oriental aroma. Sandalwood is a special parasitic plant, and it takes a long time to extract sandalwood oil, so white sandalwood oil, like other natural fragrances, is in short supply, and its main ingredient is Synthesis of santalol has attracted worldwide attention, but the synthesis methods proposed so far generally require a large number of steps to synthesize the side chain moiety and have low yields, so they cannot be called industrial production methods. According to the research conducted by the present inventors, the cispentene derivative of the present invention represented by the general formula () enables the industrial production of β-santalol, for example, by the following route. According to the present invention, the cispentene derivative represented by the general formula () can be produced by the following method. That is, by reacting 3-methyl-5,6-dihydro-2H-pyran with triarylphosphine dibromide or triarylphosphine dichloride, the general formula () [2Z]-1,5-dihalo-2-methyl-2 represented by (wherein X represents a bromine or chlorine atom)
- obtaining pentene and reacting it with an alkali metal compound represented by the following general formula () R ¹ OM () (wherein R ¹ represents a lower acyl group or benzyl group, and M represents an alkali metal); By the general formula () A cispentene derivative represented by the formula (wherein X and R ¹ each have the above-mentioned meanings) is obtained. The reaction of triarylphosphine dibromide or triarylphosphine dichloride (hereinafter sometimes referred to as triarylphosphine dihalide for convenience) and 3-methyl-5,6-dihydro-2H-pyran usually takes about At a reaction temperature of 60-100°C, preferably for example chloroform,
Carbon tetrachloride, dichloroethane, chlorobenzene,
This is carried out under dilution with a solvent inert to the reaction, such as acetonitrile. The solvent may be a single solvent or a mixed solvent. Triarylphosphine dihalide is preferably used in a proportion of about 0.8 to 1.5 moles per mole of 3-methyl-5,6-dihydro-2H-pyran. Triarylphosphine dihalides used in the present invention include triphenylphosphine dibromide, triphenylphosphine dichloride, tritolylphosphine dibromide, tritolylphosphine dichloride, tolyldiphenylphosphine dibromide, tris(chlorophenyl)phosphine dichloride, etc. I can give an example. Since triarylphosphine dihalide is easily obtained by simply mixing triarylphosphine with bromine or chlorine, 3-methyl-5,6-dihydro-2H-pyran and triarylphosphine dihalide can be easily obtained by simply mixing triarylphosphine with bromine or chlorine. Instead of triarylphosphine dihalide, triarylphosphine and bromine or chlorine may be introduced into the reaction system to generate triarylphosphine dihalide on the spot. [2Z]-1,5-dihalo-2-methyl-
2-pentene (crude) is obtained. The reaction between [2Z]-1,5-dihalo-2-methyl-2-pentene represented by the general formula () and an alkali metal compound represented by the general formula () is usually carried out by
The reaction is carried out at a reaction temperature of about -30°C to +50°C, preferably -20°C to +25°C, preferably in the presence of an aprotic polar solvent such as dimethylformamide, hexamethylphosphoramide, N-methylpyrrolidone and the like. In the general formula (), R ¹ is an acetyl group, a propionyl group, a butyryl group, or a benzyl group, and M is an alkali metal such as sodium or potassium, and particularly preferably sodium. The alkali metal compound represented by the general formula () is [2Z]-1,5-dihalo-2-
It is used in a proportion of about 0.8 to 2 mol, preferably about 1.2 to 1.8 mol, per 1 mol of methyl-2-pentene. After the reaction, the desired compound represented by the general formula () can be obtained by conventional separation means. EXAMPLES The present invention will be explained below with reference to Examples, but the present invention is not limited in any way by these Examples. Reference example 1 1 Synthesis of 3-formyl-5,6-dihydro-2H-pyran Acrolein 140g (2.5 mol), water 700g, 36%
140 g of hydrochloric acid and 72 c.c. of toluene were placed in a flask with an internal volume of 2, fitted with a Zimrow condenser, and heated to reflux on a water bath. After about 1 hour of reaction, the mixture was allowed to cool, the contents were taken out and filtered under suction, the filtrate was separated into an organic layer and an aqueous layer, and the aqueous layer was extracted with diethyl ether. The above organic layer and diethyl ether extract were combined and thoroughly washed with saturated brine, and traces of hydrochloric acid were removed with an aqueous sodium carbonate solution. Then, the 3-formyl-
5,6-dihydro-2H-pyran (bp82-84
C/15 mmHg; n ²⁰ 1.4969) was obtained in a yield of 30%. 2 3-hydroxymethyl-5,6-dihydro-
Synthesis of 2H-pyran: Add absolute ethanol to a 200 ml three-necked flask equipped with a dropping funnel, condenser, and thermometer.
80 c.c. and 2 g (0.0529 mol) of NaBH ₄ were added, and a stirrer was attached. 20 g of the above 3-formyl-5,6-dihydro-2H-pyran from the dropping funnel.
(0.1785 mol) and 40 c.c. of absolute ethanol were added dropwise.
As this was added dropwise, it generated a lot of heat, so the dropping rate was adjusted to keep the reaction temperature at 25°C. After the dropwise addition was completed, the mixture was stirred and left at room temperature for about 1 hour. Then about 3
g of water was added, ethanol was removed using an evaporator, and ammonium chloride powder was added for neutralization.
This was extracted with diethyl ether, the extract was washed with an aqueous solution of sodium bisulfite (30%) to remove unreacted aldehyde, and then distilled under reduced pressure.
-Hydroxymethyl-5,6-dihydro-2H-
Pyran (bp 78-80°C/0.7mmHg; n ²⁰ _D 1.4870) was obtained in 67% yield. 3 Synthesis of 3-methyl-5,6-dihydro-2H-pyran A four-necked flask equipped with a dropping funnel, condenser, gas inlet and stirrer was placed on a dry ice-methanol bath, and liquid ammonia 200c. c., and quickly added 2.5 g (0.109 mol) of metallic sodium to dissolve it in liquid ammonia. Next, nitrogen gas is blown in to block the liquid surface from oxygen, and 3-hydroxymethyl-
A mixture of 4.5 g (0.046 mol) of 5,6-dihydro-2H-pyran, 1.5 g (0.046 mol) of anhydrous methanol and 20 c.c. of anhydrous diethyl ether was slowly added dropwise to carry out the reaction at -50°C. Stirring was continued for 1 hour even after the dropwise addition was completed. At that time, the color of the solution changed from blue ink color to white, indicating the completion of the reaction. Finally, 20 c.c. of diethyl ether was added, the flask was lifted from the bath, and the liquid ammonia was gradually vaporized and dissipated. After the liquid ammonia was completely volatilized, an equivalent amount of concentrated hydrochloric acid was added to neutralize the sodium methoxide in the reaction system. Next, it was extracted with diethyl ether, the extract was washed with saturated saline, dried over magnesium sulfate, the diethyl ether was distilled off at normal pressure, the pressure was reduced to about 10 mmHg using an aspirator, and the remaining ether and 3-methyl-5 , 6-dihydro-2H-pyran was trapped. This was distilled under atmospheric pressure to obtain 3-methyl-5,6-dihydro-2H-pyran (bp115~
116°C/760mmHg; n ²⁰ _D 1.4460) (consumed 3-hydroxymethyl-5,6-dihydro-2H
- 60% yield based on pyran). Reference Example 2 A four-necked flask with an internal volume of 200 ml was equipped with a magnetic stirrer, a cooling condenser with a salt cap tube, a dropping funnel, and a thermometer, and 6.8 g (0.026 mol) of triphenylphosphine and dried acetonitrile were placed in the flask. I put in 30c.c. The reaction flask was brought to 0°C in an ice bath while stirring well with a magnetic stirrer. Slowly drop 4.2 g (0.026 mol) of bromine from the dropping funnel and lower the temperature.
The temperature was kept below 10℃. After the dropwise addition was completed, the mixture was stirred for 30 minutes, 60 c.c. of dry chlorobenzene was added, the ice bath was replaced with an oil bath, and the temperature was gradually raised to reflux temperature. 3-Methyl-5,6-dihydro- through a dry addition funnel.
2H-pyran 2.4g (0.024mol) and chlorobenzene
10 c.c. was mixed and slowly dripped. After refluxing for 20 hours, the temperature of the reaction vessel was lowered to room temperature. Next, first, acetonitrile and chlorobenzene were removed under reduced pressure, crystalline triphenylphosphine oxide was separated by suction, and the crystals were washed with dry pentane. After combining the liquid and the washing liquid and distilling off low-boiling substances such as the solvent under reduced pressure at room temperature, the residue was distilled under reduced pressure [2Z]-1,5
-3.6g of dibromo-2-methyl-2-pentene
(yield 62%). This product has a boiling point of 70℃/0.2
mmHg, and showed the following NMR spectrum. NMR (δ) 1.90 (s, 3H) 2.60 (m, 2H) 3.45 (t, 2H) 3.95 (m, 2H) 6.00 (m, 1H) ppm. Example 1 Performed except that purification by vacuum distillation was not performed. By repeating Example 1, 4 g of crude 1,5-dibromo-2-methyl-2-pentene (crude product yield
69%). Next, this 1,5-dibromo-2-
Internal volume of methyl-2-pentene in unpurified form
Place in a 100 c.c. Erlenmeyer flask and add 40 c.c. of dry dimethylformamide and 2.1 g of anhydrous sodium acetate.
was added, tightly capped and stirred at room temperature for 12 hours, then 20c.c.
water, extracted 5 times with a mixture of n-hexane-diethyl ether (1:1), and the organic layer (extract liquid)
was washed with saturated brine, dried by adding magnesium sulfate, and low-boiling substances were removed under reduced pressure to obtain the crude product 2.6.
g (yield 70%) was obtained. This crude product was distilled as a fraction with a boiling point of 70-72℃/0.4mmHg [2Z]-1-
2.4 g (yield 64%) of acetoxy-5-bromo-2-methyl-2-pentene was obtained. of this product
The NMR spectrum was as follows. NMR (δ) 1.90 (s, 3H) 2.00 (s, 3H) 2.60 (t, 2H) 3.40 (t, 2H) 4.60 (m, 2H) 6.20 (m, 1H) ppm. Example 2 In 10 ml of benzyl alcohol metallic sodium
0.23g (0.01 mol) was dissolved, and then [2Z]-1,5-dibromo-2-methyl-2 was added to the solution under ice cooling.
- 2.16 g (0.009 mol) of pentene was added and stirred overnight at the same temperature. After the reaction, benzyl alcohol was distilled off from the reaction mixture under reduced pressure, and the residue was treated with silica gel column chromatography (using a 1:9 mixture of isopropyl ether:hexane as a developing solvent) to obtain [2Z]-1- Benzyloxy-5-bromo-2-methyl-2-pentene was obtained in a yield of 48%. The results of elemental analysis of the product were as follows. Calculated value (as C ₁₃ H ₁₇ BrO)
C: 58.00 H: 6.37, actual value C: 57.86 H: 6.12 Examples 3 and 4 In Example 1, 2.1 g of anhydrous sodium acetate
The reaction was carried out in the same manner as in Example 1 except that 2.46 g of anhydrous sodium propionate or 2.82 g of anhydrous sodium butyrate was used instead of Corresponding [2Z]-1
-Propionyloxy-5-bromo-2-methyl-2-pentene (Example 3) or [2Z]-1-
Butyryloxy-5-bromo-2-methyl-2-
Pentene (Example 4) was obtained. The results are shown in Table 1. 【table】

Claims (1)

[Claims] 1 General formula () (In the formula, X represents a bromine or chlorine atom, and R ¹
represents an acetyl group, a propionyl group, a butyryl group, or a benzyl group). 2 By reacting 3-methyl-5,6-dihydro-2H-pyran with triarylphosphine dibromide or triarylphosphine dichloride, the general formula () (In the formula, X represents a bromine or chlorine ^atom .) ¹ represents an acetyl group, a propionyl group, a butyryl group, or a benzyl group, and M represents an alkali metal. (In the formula, X and R ¹ each have the above meanings.) A method for producing a cispentene derivative represented by the following formula.