JPS6210494B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides (Z)-3-nonenal, (Z)-3-
The following formula (A) includes a fragrance component such as (Z)-6-nonadienal, However, in the formula, R is a C ₁ -C ₁₆ alkyl group, C ₂ -
It _{is represented by} ( The following formula (1) useful as a production intermediate for Z)-3-alkenals, However, in the formula, R has the same meaning as described above for formula (A), and R' represents a C ₁ to C ₃ alkyl group. More specifically, the following formula (2), However, in the formula, R' represents a C ₁ - C ₃ alkyl group. By reacting 4,4-dialkoxy-1-butyne represented by the following with a Grignard reagent or an alkali metal amide, the product and the following formula ( 3) R-X (3) However, in the formula, R is a _C1 - _C16 alkyl group, _C2-
Alkyl represented by a group selected from the group consisting of a C ₁₆ alkenyl group, a C ₃ to _{C 16} alkynyl group, and an aryl group, and X represents a group selected from the group consisting of halogen, mesyl, and tosyl. The following formula (1) is characterized by reacting with a curing agent. However, in the formula, R and R' have the same meanings as above, and relates to a method for producing 1,1-dialkoxy-3-alkynes represented by (Z)-3-nonenal and (Z)-3-(Z)-6-nonadienal included in the above formula (A) are compounds isolated from watermelon essential oil, which is a natural source, and are important compounds in watermelon essential oil. It is one of the aroma components and has high value as a base material for perfume preparation, as it significantly enhances the aroma. Conventionally, Helv.Chim.
Acta. vol. 46 , p. 1792 (1963) contains the following process formula,

According to the table, methods for synthesizing the above compounds are described. HC≡C-CH=CHOCH ₃ used in the above conventional method
In addition to the disadvantage of being an expensive raw material, the formula
There is a drawback that two steps are required to synthesize the compound of formula (1)′ included in (1). Furthermore, in the conventional method, the above R″-C≡C-
The yield of CH=CHOCH ₃ is 47-73%, the yield of the above formula (1)' compound from this compound is 72%, and the yield of the formula (1)' compound from the above raw material compound is about 53%. degree and low yield. Furthermore, the formula R″-C≡C-CH=
The formation of the compound of formula (1)' from CHOCH ₃ may involve an undesirable isomerization reaction, and troubles are also difficult to avoid in this respect. The present inventors conducted research in order to overcome the deficiencies of the conventional methods as described above and provide an improved method for producing the intermediates of the formula (1), including the compounds of the formula (1)'. As a result, for example, from 4,4-dialkoxy-1-butyne of the formula (2), which can be easily synthesized in high yield from propargyl halide and orthoformic acid ester, the formula (1) can be synthesized in one step. It has been discovered that 1,1-dialkoxy-3-alkynes can be easily synthesized in high yields of about 90% or more and without the trouble of inconvenient isomerization reactions. Therefore, an object of the present invention is to provide an improved method for industrially advantageously producing the 1,1-dialkoxy-3-alkynes of the formula (1). The above objects and many other objects and advantages of the present invention will become more apparent from the following description. According to the method of the present invention, the 4,4-dialkoxy-1-butyne of the formula (2) is allowed to react with a Grignard reagent or an alkali metal amide, and the product is reacted with the alkylating agent of the formula (3). By this,
In one step operation, the formula (1) 1,1-dialkoxy-
3-Alkynes can be produced with high yield and high purity. The compound of formula (1) thus obtained is
After being converted into (Z)-3-alkenal dialkyl acetal represented by the following formula (B) by catalytic hydrogen reduction in the presence of Lindlar catalyst (reduction catalyst) by a method known per se, the acidic (Z) of the above formula (A) by hydrolysis in the presence of a catalyst
- Can be used to produce 3-alkenals. In addition to this known step, the method of the present invention can be schematically illustrated as follows.

[Table] Formula (B) Formula (A)
(In the formula, R and R'X have the same meanings as above)
The above formula (2) 4,4-dialkoxy-1-butyne can be easily produced, for example, by reacting propargyl bromide with aluminum and orthoformate. According to the method of the present invention, 4,4-dialkoxy-1-butyne of the formula (2), which can be obtained as described above, is reacted with a Grignard reagent or an alkali metal amine, and the product and the alkyl of the formula (3) are reacted. By reacting with a compounding agent, the desired formula (1) 1.1
-Dialkoxy-3-alkynes can be easily obtained. The reaction can be carried out by adding 4,4-dialkoxy-1-butyne of formula (2) to a Grignard reagent or alkali metal amide solution in a solvent, and then adding and contacting an alkylating agent of formula (3). . This reaction can be carried out in one step by sequentially contacting 4,4-dialkoxy-1-butyne of the formula (2) with a Grignard reagent or an alkali metal amide, and then with the alkylating agent of the formula (3). can be selected as appropriate. The reaction can be carried out over a wide temperature range, for example from about -80°C to about +150°C, preferably at about -
Temperatures such as 70°C to about +70°C may be exemplified. The reaction time is appropriately selected depending on the type of reaction reagent, reaction time, etc., but for example, from about 1 to about
An example of a reaction time range is about 10 hours. The reaction molar ratio can also be selected appropriately, for example, formula (2) 4・4-
About 0.5 to about 1 mole of dialkoxy-1-butyne
10, more preferably about 1 to about 1.5 moles of Grignard reagent or alkali metal amide, and about 0.5 moles per 4,4-dialkoxy-1-butyne.
The amount of alkylating agent used can be exemplified from about 10 moles to about 10 moles, more preferably from about 1 to about 1.5 moles. Specific examples of the above formula (2) 4,4-dialkoxy-1-butyne include: 4,4-dimethoxy-1-butyne 4,4-diethoxy-1-butyne 4,4-dipropyloxy-1 - Compounds such as butyne may be exemplified. Examples of Grignard reagents include methylmagnesium chloride, ethylmagnesium bromide, ethylmagnesium chloride, allylmagnesium chloride, and examples of alkali metal amides include lithium amide, sodium amide, potassium amide, etc. Amide, etc. can be exemplified. Specific examples of the solvent used in the above reaction include ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, dimethoxyethane, diglyme, tetrahydrofuran, and dioxane;
Hydrocarbon solvents such as n-hexane; also, for example,
Examples include liquid ammonia. These solvents can be used alone or in combination of two or more. There is no particular restriction on the amount of these solvents to be used, but for example, they may be used in an amount of about 1 to about 200 times, more preferably about 5 to about 50 times, the weight of the compound of formula (2) as a raw material. Quantities can be exemplified. After the completion of the above reaction, for example, the reaction product is poured into saturated ammonium chloride water, the reaction solution is decomposed, extracted with an appropriate solvent, the solvent layer is washed with water, dried and concentrated to obtain the compound of formula (1). It can be obtained in high yield and high purity. If desired, further purification can be achieved by distillation under reduced pressure. As described above, formula (1) obtained by the method of the present invention
1,1-Dialkoxy-3-alkynes can be converted to (Z )-3-alkenal dialkyl acetal and further hydrolyzed in the presence of an acidic catalyst to convert (Z)-3-alkenal of the formula (A), such as (Z)-3-nonenal,
It can be advantageously used in the production of perfume substances such as (Z)-3-(Z)-6-nonadienal. The above formula (B) compound can be produced, for example, by subjecting the formula (1) compound to a catalytic hydrogen reduction reaction in an inert organic solvent in the presence of a reduction catalyst such as poisoned palladium. can be easily carried out with excellent selectivity. The reaction proceeds satisfactorily even at room temperature, and can be carried out, for example, at a temperature of about 5°C to about 40°C, and more preferably a temperature range of about 10°C to about 30°C. Although the reaction proceeds satisfactorily under normal pressure, pressurized conditions can also be used, and
Pressure ranges of the order of Kg/cm ² are often employed. Catalysts such as poisoned palladium suitable for use in the above catalytic reduction reaction include, for example:
Palladium poisoned with lead acetate (Rindler catalyst)
and palladium-barium sulfate to which quinoline or the like is added. The amount of these catalysts to be used is, for example, approximately
About 0.1 to about 20% by weight, more preferably about 0.5 to about
A content of around 10% by weight is most often employed. Examples of the inert solvent used in the catalytic hydrogen reduction reaction include methanol, ethanol, n-propanol, isopropyl alcohol, ethyl acetate, hexane, and petroleum ether. These solvents may be used alone or in a mixture of two or more. There is no particular restriction on the amount of these solvents used, but for example, about 5 to about
About 300 times the weight, preferably about 10 to about 100 times the weight, is often employed. After the catalytic hydrogen reduction reaction, the catalyst used is separated, the liquid is washed with water, dried, and concentrated, whereby the compound of formula (B) can be obtained in good yield and excellent selectivity. If desired, further purification can be achieved by distillation under reduced pressure. In addition, in order to produce the (Z)-3-alkenals of the formula (A) from the (Z)-3-alkenal dialkyl acetals of the formula (B), in the presence of an acidic catalyst, in a suitable solvent. , can be easily produced with high yield and good selectivity by hydrolysis. This hydrolysis reaction is, for example, about 0
Temperature range from ゜~about 50℃, preferably about 10゜~
A temperature range of approximately 35°C is adopted. The reaction time can be changed appropriately depending on the reaction temperature, etc., for example, about 10
An example of a reaction time is about 50 hours. Specific examples of acidic catalysts used in the hydrolysis reaction include sulfuric acid, hydrochloric acid, phosphoric acid, para-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, trichloroacetic acid, dichloroacetic acid,
In addition to monochloroacetic acid, trifluoroacetic acid, difluoroacetic acid, monofluoroacetic acid, oxalic acid, formic acid, etc., examples include conjugate acids such as pyridine hydrochloride, strong acidic ion exchange resins, and the like. The amount of these used is about 0.1 to about 5
About twice the molar amount, preferably about 0.1 to about 0.5 times the molar amount, is often employed. Solvents used in the reaction include polar solvents such as water, methanol, and ethanol, as well as hydrocarbon solvents such as benzene, toluene, and hexane, and examples such as diethyl ether, diisopropyl ether, dimethoxyethane, and dimethoxy. Examples include ether solvents such as methane, tetrahydrofuran, and dioxane. These solvents can be used alone or in combination of two or more, and there are no special restrictions on the amount used, but it is about 5 to about 50 times the weight of the compound of formula (B) above. , more preferably from about 3 to
An example of an amount used is about 30 times the weight. After the completion of the above hydrolysis reaction, for example, the reaction product is poured into water, extracted with an appropriate solvent, the solvent layer is washed with a 5% aqueous sodium carbonate solution, then washed with water, dried, and concentrated to obtain the formula (A ) (Z)-3-alkenals can be obtained in high yield and purity. If desired, it can be further purified by means such as vacuum distillation or column chromatography. Hereinafter, several embodiments of the present invention will be explained in more detail with reference to Examples. Reference Example 1 Synthesis of 4,4-diethoxy-1-butyne 20 ml of tetrahydrofuran and 2.5 g of aluminum chips were placed in a reaction vessel and heated at a temperature of 60 to 65°C.
The reaction was carried out by dropping 10 g of propargyl bromide while stirring for 30 minutes. 60-65 after completion of dripping
After continuing the reaction at ℃ for another hour, the reaction solution was diluted to 10
Cooled to ℃. After cooling, at a temperature of 10-20℃ about 30
While stirring for minutes, 15 g of ethyl orthoformate was added dropwise to carry out the reaction. After the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour to complete the reaction. The reaction solution was poured into 100 ml of saturated ammonium chloride aqueous solution and extracted with ether. The ether layer was washed with water, separated and purified to obtain 9.5 g of pure 4,4-diethoxy-1-butyne having a boiling point of 50-51°C/7 mmHg. (Theoretical yield 84%) Example 1 Synthesis of 1,1-diethoxy-3-hexyne Charge liquid ammonia 1 into a reaction vessel, and -35
27.6 g of sodium metal and ferric nitrate were added while stirring for about 40 minutes at a temperature of ˜-40° C. to form sodium amide. -35 to -40 in the reaction solution
4.4 g of 142 g while stirring for about 30 minutes at a temperature of ℃.
-Diethoxy-1-butyne was added dropwise, and after the addition was completed, the reaction was further stirred at a temperature of -35 to -40°C for 1 hour. Next, 130 g of ethyl bromide was added dropwise into the reaction solution while stirring for 30 minutes at -35 to -40°C, and after the dropwise addition was completed, the reaction was further stirred at a temperature of -35 to -40°C for 1 hour.
After the reaction was completed, liquid ammonia was collected, and the residue was poured into a saturated aqueous ammonium chloride solution and extracted with ether. Separate and purify according to conventional methods to obtain a boiling point of 85~
154 g of pure 1,1-diethoxy-3-hexyne with a temperature of 86°C/15 mmHg were obtained. (Theoretical yield 91%) Example 2 Synthesis of 1,1-diethoxy-3,6-nonadiyne 30 ml of tetrahydrofuran and 4.8 g of metal magnesium chips were placed in a reaction vessel, and 32.8 g was added under water cooling.
A mixture of ethyl bromide and 30 ml of tetrahydrofuran is added dropwise at room temperature with stirring. After dripping, 28.4
A mixture of g of 4,4-diethoxy-1-butyne and 30 ml of tetrahydrofuran was added dropwise at room temperature with stirring. After the dropwise addition, tetrahydrofuran is further stirred and reacted under reflux for 2 hours. Then 20g
A mixture of 1-bromo-2-pentyne and 30 ml of tetrahydrofuran was added dropwise at room temperature with stirring. After completion of the dropwise addition, the mixture is further stirred and reacted at room temperature for 1 hour. After the reaction is completed, the mixture is poured into a saturated aqueous ammonium chloride solution to extract ether. Separate and purify according to conventional methods, boiling point 113-115℃/3mmHg
26 g of pure 1,1-diethoxy-3,6-nonadiyne having the following properties are obtained. (Theoretical yield 89%) Reference example 2 Synthesis of 1,1-diethoxy-(Z).(Z)-3,6-nonadiene 1,1-diethoxy-3.
Prepare 25 g of 6-nonadiyne, 240 ml of methanol, 3.2 g of quinoline, and 3.2 g of Lindlar catalyst at room temperature.
The reaction is stirred at a maximum hydrogen pressure of 10 kg/cm ² until the theoretical amount of hydrogen is absorbed. After the reaction is completed, the catalyst is separated from the reaction solution and methanol is recovered from the solution. Add 50 ml of ether to the residue, wash with water, wash with 5% hydrochloric acid, wash with water, wash with saturated heavy acid, and wash with water. Separation and purification were performed according to conventional methods to obtain pure 1,1-diethoxy-cis, cis-3,6 having a boiling point of 91-93℃/3 mmHg.
- Obtain 23 g of nonadiene. (Theoretical yield 90%) Reference example 3 Synthesis of (Z)・(Z)-3・6-nonadienal In a reaction vessel, 30 ml of 0.5N hydrochloric acid aqueous solution, 3 g of 1・1-diethoxy-cis, cis-3・6-nonadiene
and react with stirring at room temperature for 20 hours. After the reaction is complete, extract with ether. Separation and purification is performed according to a conventional method to obtain 1.5 g of pure cis, cis-3,6-nonadienal having a boiling point of 70-72°C/3 mmHg. (Theoretical yield 75%)

Claims (1)

[Claims] 1. The following formula (2), However, in the formula, R' represents a C ₁ - C ₃ alkyl group. By reacting 4,4-dialkoxy-1-butyne represented by the following with a Grignard reagent or an alkali metal amide, the product and the following formula ( 3) R-X (3) However, in the formula, R is a _C1 - _C16 alkyl group, _C2-
represents a group selected from the group consisting of a C ₁₆ alkenyl group, a C ₃ to _{C 16} alkynyl group, and an aryl group, and X represents a group selected from the group consisting of halogen, mesyl, and tosyl; The following formula (1) is characterized by reacting with a curing agent. However, in the formula, R and R' have the same meaning as above. A method for producing 1,1-dialkoxy-3-alkynes represented by: