JPS6154772B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides the following formula (1) which is not only useful as a fragrance substance itself, but also useful as a synthetic intermediate for diasmonoid fragrance compounds, and also as a synthetic intermediate for pharmaceuticals, agricultural chemicals, etc. However, in the formula, R is CH ₃ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ −
basis,

【formula】

The present invention relates to a new method for producing 4-oxoalkanals, a known compound represented by the formula: CH ₃ CH ₂ C≡CCH ₂ CH ₂ - group, and X represents a halogen atom. More specifically, the present invention is based on the following formula (3) However, in the formula, n represents 2 or 3. 4,4-Polymethylenedioxybutyronitrile represented by the following formula (4) RMgX (4) However, in the formula, R is CH ₃ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ −
base,

【formula】

[Formula] represents a group or a CH ₃ CH ₂ C≡CCH ₂ CH ₂ - group, and X represents a halogen atom. The following formula (2) is formed by reacting with a Grignard reagent represented by However, in the formula, R and n have the same meanings as above, and the following formula (1) is characterized by reacting an acidic catalyst with a 4-oxo-1,1-polymethylenedioxy compound represented by: However, in the formula, R has the same meaning as above, and relates to a method for producing a 4-oxoalkanal represented by: Conventionally, various proposals have been made for the synthesis of 4-oxoalkanals of the above formula (1), but the reality is that no satisfactory synthesis method suitable for implementation on an industrial scale has been provided. It is. For example, Tetra−
hadron Letters 1978 (52) 5175-5178 contains the following formula, A method for synthesizing 4-oxo-cis-7-decenal, which is included in the above formula (1), is described through multiple steps shown in (LDA: lithium diisopropylamide, HMPA: hexamethyl phosphoramide). According to this method, decenal can be obtained in a good yield, but in addition, it requires a low temperature reaction operation and equipment of -78°C, which is disadvantageous industrially. There are troubles and disadvantages that make it difficult to adopt it industrially, such as the use of HMPA which is not suitable for the above formula, and the fact that three steps are required to form the decenal from the nitrile (a) in the above formula. The present inventors have conducted research to overcome the disadvantages or deficiencies of the above proposal and have found that the above conventional method The following formula (3) can be synthesized cheaply and easily compared to However, in the formula, n represents 2 or 3. The compound of formula (1) can be industrially advantageously produced from 4,4-polymethylenedioxybutyronitrile in a shortened process in high yield and with high purity. discovered that it is possible to produce Therefore, an object of the present invention is to provide a method for producing the compound of formula (1) using a new process that is industrially advantageous and shortened. 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-oxoalkanates of the formula (1) are deacetalized by reacting the 4-oxo-1,1-polymethylenedioxy compound of the formula (2) with an acidic catalyst. It can be easily obtained with high yield and high purity by reaction.
Further, the compound of formula (2) is 4.4 represented by the above formula (3).
-Polymethylenedioxybutyronitrile is prepared, for example, in the presence of an inert catalyst, by the formula (4)RMgX [where R
can be easily obtained by reacting with a Grignard reagent as defined above for formulas (1) and (2). The method of the present invention can be schematically illustrated as follows. 4,4-Polymethylenedioxybutyronitrile of the above formula (3) can be obtained by desalting 1,1-polymethylenedioxy-3-halogenopropane with a metal cyanide compound, for example, as shown in the following formula. can be easily manufactured. The details are Japanese Patent Application No. 54-141173 filed by the same applicant.
(Japanese Patent Publication No. 56-65839). However, in the formula, X represents halogen and M represents an alkali metal, alkaline earth metal, etc. Formula (2) 4-oxo-1.1- used in the method of the present invention
The polymethylenedioxy compound can be obtained, for example, as described above, and is represented by 4 or 4 of the above formula (3).
- polymethylenedioxybutyronitrile of the above formula
(4) The 4-oxo-1,1-polymethylenedioxy compound of formula (2), which can be easily formed by a Grignard reaction in which it is brought into contact with Grignard reagents, for example in an inert solvent, can be formed using an acidic catalyst. By reacting with the compound, a deacetalization reaction can be carried out and the compound can be easily converted into the 4-oxo-alkanal of formula (1). The Grignard reagent of the formula (4) used in the above Grignard reaction is prepared according to a known method, for example, by combining metal magnesium with the following formula (5) RX (5) in an inert solvent, where X represents a halogen and R is as described above. It can be easily obtained by contacting with an alkyl halide represented by the same meaning. In the Grignard reaction, for example, the Grignard reagent of the formula (4) obtained as described above is brought into contact with 4,4-polymethylenedioxybutyronitrile of the formula (3) dropwise, and then the Grignard reaction product is reacted under weakly acidic conditions. By decomposing , the compound of formula (2) can be easily produced with good yield and purity. The reaction can be carried out over a wide temperature range, for example from about -30°C to about +100°C, with a more preferred example being a temperature range from about 0°C to about 50°C. The dropwise addition and reaction time can be changed as appropriate depending on the reaction temperature and the like, and for example, a reaction time of about 1 hour to about 5 hours can be exemplified. In addition, the magnesium compound of the formula (4) compound used in the Grignard reaction is the raw material of the formula (3).
The amount used is often, for example, about 1 to 1.5 mol, preferably about 1.2 mol, per 1 mol of the compound. Further, specific examples of the inert solvent used in the Grignard reaction include ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, dimethoxyethane, diglyme, tetrahydrofuran, and dioxane, and carbonized solvents such as benzene, toluene, and hexane. Examples include hydrogen-based solvents. These solvents can be used alone or in combination. There is no particular restriction on the amount of these solvents used, but for example, about 1 to about
For example, the amount used is about 200 times by weight, more preferably about 5 to about 50 times by weight. After completion of the Grignard reaction, for example, a dilute aqueous acid solution, for example, a 1% aqueous hydrochloric acid solution, is added dropwise to the reaction product to cause a decomposition reaction. This dripping and decomposition reaction is
When the reaction temperature is set, for example, in the temperature range of about 0° to about 50°C, the reaction time can be about 2 to about 10 hours. After completion of the decomposition reaction, the compound of formula (2) can be obtained in high yield and purity by extracting with a suitable solvent, washing the solvent layer with water, drying, and concentrating. If desired, further purification can be achieved by distillation under reduced pressure. In the present invention, in order to produce the 4-oxoalkanals of the formula (1) from the 4-oxo-1,1-polymethylenedioxyalkanes of the formula (2), in the presence of an acidic catalyst, for example, a suitable It can be easily produced with high yield and good selectivity by hydrolysis in a solvent. This hydrolysis reaction can be carried out, for example, in a temperature range of about 0°C to about 50°C, preferably in a temperature range of about 10 to 35°C. The reaction time can be changed as appropriate depending on the reaction temperature and the like, and for example, a reaction time of about 50 to 10 hours can be exemplified. Specific examples of acidic catalysts used in the above hydrolysis reaction include sulfuric acid, hydrochloric acid, phosphoric acid, p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, trichloroacetic acid, dichloroacetic acid, monochloroacetic acid, trifluoroacetic acid. , difluoroacetic acid, monofluoroacetic acid, oxalic acid, formic acid, etc., as well as conjugate acids such as pyridine hydrochloride, and strongly acidic ion exchange resins such as IR-120. The amount to be used is about 0.1 to about 5 times the mole of the compound of formula (2), more preferably about 0.1 to about 5 times.
A value of about 0.5 times the mole is often adopted. Examples of solvents used in the reaction include water, methanol,
In addition to polar solvents such as ethyl alcohol, hydrocarbon solvents such as benzene, xylene, toluene, and hexane, and diethyl ether,
Examples include solvents such as ethers such as diisopropyl ether, dimethoxyethane, dimethoxymethane, tetrahydrofuran, and dioxane. These solvents can be used alone or in combination of two or more, and there are no particular restrictions on the amount used, but about 5 to 50 times the weight of the compound of formula (2), More preferably, the amount used is about 3 to 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 ( 1) Straight chain
_C104 -oxo-saturated and unsaturated aldehydes can be obtained in high yield and purity. If desired, it can be further purified by means such as vacuum distillation or column chromatography. It should also be noted that the deacetalization reaction conditions for obtaining 4-oxoalkanals of formula (1) from 4-oxo-1,1-polymethylenedioxyalkanes of formula (2) are applied to the Grignard reaction and decomposition conditions described above. Then, the compound of formula (1) can be obtained in one step without isolating and purifying the compound of formula (2). Hereinafter, several aspects of the present invention will be explained in more detail with reference to Examples. For practical purposes 1. Method for producing 4-oxodecanal. With hexyl bromide (0.1 mol), magnesium (0.11 mol), and 50 ml of dry diethyl ether,
Prepare Grignard reagent. In this Grignard reagent solution, 2-(2-cyanoethyl)-1,3-
A 50 ml solution of dioxolane (0.1 mol) in ether
Add dropwise at 30-35°C. After the dropwise addition was completed, the mixture was left at room temperature overnight, and the reaction solution was poured into 200 ml of 10% sulfuric acid water, and stirring was continued at room temperature for 10 hours. After the reaction was completed, the aqueous layer was extracted with 100ml of ether.
Combine organic layers. After neutralizing and washing with 200 ml of sodium chloride water, drying with magnesium sulfate and recovering ether yields crude 4-oxodecanal. The boiling point is purified by distillation under reduced pressure.
12 g (70% yield) of 4-oxodecanal with 88-90°C/3 mmHg was obtained. Example 2 Method for producing 4-oxo-cis-7-decenal. Cis-3-hexenyl chloride (0.1 mol) in place of hexyl bromide in Example 1
A similar Grignard reaction operation is performed using Next, instead of 10% sulfuric acid water, add 1% hydrochloric acid water 200%
Perform the reaction treatment in ml. Thereafter, by performing the same post-treatment operation, 15.3 g of 1,1-ethylenedioxy-cis-7-decen-4-one (boiling point
115-118°C/3 mmHg, 71% yield). Next, by reacting with 50 ml of 10% sulfuric acid water at room temperature to deacetalize, and performing the same post-treatment, 4.
-Oxo-cis-7-decenal 9.6g (90-92
°C/3 mmHg, 80% yield). Example 3 Method for producing 4-oxo-trans-7-decenal. Trans-3-hexenyl chloride (0.1 mol) in place of hexyl bromide in Example 1
and 2-(2-cyanoethyl))- instead of 2-(2-cyanoethyl)-1,3-dioxolane.
Using 1,3-dioxane (0.1 mol), 4-oxo-
Trans-7-decenal 13g (boiling point 90-92℃/
3 mmHg, 76% yield). Example 4 Preparation of 4-oxo-7-decyne-1-al. By using 3-hexynyl bromide (0.1 mol) in place of hexyl bromide in Example 3 and carrying out the same reaction procedure, 4
-oxo-7-decyne-1-al 7g (boiling point 98
~100°C/3mmHg, 42% yield).

Claims (1)

[Claims] 1 The following formula (3) However, in the formula, n represents 2 or 3. 4,4-Polymethylenedioxybutyronitrile represented by the following formula (4) RMgX (4) However, in the formula, R is CH ₃ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ −
The following formula (2) is formed by reacting with a Grignard reagent represented by a group, [Formula] [Formula] group or CH ₃ CH ₂ C≡CCH ₂ CH ₂ - group, and X represents a halogen atom. , However, in the formula, R and n have the same meanings as above, and the following formula (1) is characterized by reacting an acidic catalyst with a 4-oxo-1,1-polymethylenedioxy compound represented by: However, in the formula, R has the same meaning as above. A method for producing a 4-oxoalkanal compound represented by: