JPS6113696B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention utilizes a reaction method different from conventional proposals to synthesize the following formula (1), R ¹ CH, which is useful for the synthesis of perfumes, agriculture, pharmaceuticals, etc., and is also useful as a perfume itself. ₂ CH ₂ CHO (1) However, in the formula, R ¹ is a C ₁ - C ₂₀ alkyl group, C ₂ -
Known aliphatic aldehydes represented by the following represent a C ₂₀ alkenyl group or a C ₂ to _{C 20} alkynyl group, which can be industrially advantageously produced with high purity and high yield. Regarding the manufacturing method. Conventionally, various proposals have been known regarding the synthesis of aldehydes represented by the above formula (1). Typical of these proposals are: (A) Oxo method: − (B) Dehydrogenation method: − (C) Grignard method: − etc. can be mentioned. In these conventional methods,
There are restrictions on the raw materials because there are many side reactions and the purity tends to deteriorate, and compounds with double bonds are more likely to undergo isomerization because high heat is required, and raw materials are expensive for industrial use. There are many difficulties and disadvantages, such as the need for The present inventors conducted research to overcome the problems of the conventional methods as described above and to develop a method that can industrially advantageously synthesize the compound of formula (1). As a result, by using a completely different reaction method from the conventional method, without the troubles of the conventional method mentioned above,
We have discovered that aliphatic aldehydes of formula (1) can be produced. That is, according to the research of the present inventors, β
- By deacetalizing the acetals of formula (2), which can be easily obtained by the coupling reaction between halopropanal acetals and Grignard reagents, there are disadvantages such as restrictions on raw material compounds and requirements for high temperature reaction. It has been found that aldehydes of formula (1) can be easily produced with high purity and high yield without accompanying. Therefore, an object of the present invention is to provide an industrially advantageous method for producing aldehydes represented by formula (1) with high purity and high yield. The above objects, as well as many other objects and advantages of the present invention will become more apparent from the following description. Acetals of the following formula (2) of the raw materials used in the method of the present invention,

[Formula] However, in the formula, R ² is a C ₁ to C ₅ alkyl group, a benzyl group, or two R ^2s taken together (-CH ₂
) − _o (where n is 2 or 3), and R ¹ is C ₁ ~
_C20 alkyl group, preferably _C3 - _C15 alkyl group, _C2 - _C20 alkenyl group, preferably _C2 - _C12
represents an alkenyl group, or a _C2 - _C20 alkynyl group, preferably a _C3 - _C12 alkynyl group, is the following formula (3),

[Formula] In the formula, R ² has the same meaning as above, and X represents Br or I. β-halopropanal acetals represented by the following formula (4), R ¹ MgY (4) with the proviso that In the formula, R ¹ has the same meaning as described above, and Y represents a halogen atom. It can be formed by coupling a Grignard reagent represented by the following in an inert organic solvent in the presence of a coupling catalyst. According to the method of the present invention, the acetals of the formula (2) obtained as described above are subjected to a deacetalization reaction in the presence of an acid catalyst ^. ₂ CH ₂ CHO (1) where R ¹ has the same meaning as above, and a method for producing an aliphatic aldehyde represented by the following is provided. The method of the present invention can be illustrated as follows.

【formula】

The β-halopropanal acetals of the formula (3) can be prepared, for example, in the presence of an appropriate inert organic solvent or in accordance with the method known in J.Org. in the absence of the desired
For example, hydrogen bromide, hydrogen iodide, etc. are saturated in an appropriate amount of alcohols or diols having R ² (R ² is a C ₁ to _{C 5} alkyl group or benzyl group), and acrolein is added dropwise to this to react. This can be obtained by Further, the Grignard reagent of formula (4) may be, for example, a _C1 - _C20 alkyl halide, a _C2 - _C20 alkenyl halide, a _C2 - _C20 alkynyl halide in the presence of a suitable inert solvent. It can be easily produced by bringing halides into contact with metallic magnesium. The compound of formula (2) used in the method of the present invention is prepared by combining β-halopropanal acetals of formula (3) which can be formed as described above and a Grignard reagent of formula (4) in an inert organic solvent in the presence of a coupling catalyst. , can be formed by a coupling reaction. The Grignard coupling reaction, for example,
This can be carried out with good purity and yield by bringing the Grignard reagent solution of formula (4) into dropwise contact with a mixture of the compound of formula (3) and the coupling catalyst in an inert organic solvent. This coupling reaction can be carried out over a wide temperature range, for example from about -80°C to about +100°C,
A more preferable example is a temperature range of about -45°C to about +40°C. The dropping time and the reaction time can be changed as appropriate depending on the reaction temperature, the type of catalyst, etc., and can be exemplified by a reaction time of about 1 to about 50 hours, for example. The amount of the Grignard reagent of formula (4) used in the above coupling reaction can be selected as appropriate, but for example, an amount of about 1 to about 2 moles per mole of the compound of formula (3) is often adopted. . Specific examples of the coupling catalyst used in the above coupling reaction include, for example, Li ₂ CuCl ₄ ,
Cu(Acac) ₂ , AgNO ₃ , FeCl ₃ , Fe(Acac) ₃ ,
CuBr, CuCl, CuCl ₂・TMEDA [Acac: acetylacetonate, TMEDA: (CH ₃ ) ₂ NCH ₂ CH ₂ N
(CH ₃ ) ₂ ], etc. The amount of these catalysts used can be changed as appropriate depending on the type of catalyst, but for example, the amount of the catalyst used is about 0.001 to
About 0.1 mole is sufficient. Specific examples of the inert organic solvent used in the above coupling reaction include ether solvents such as diethyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, diglyme, and hydrocarbon solvents such as n-hexane and benzene. can be mentioned. 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 examples include about 1 to about 200 times the weight of the compound of formula (3), more preferably about 5 to about 50 times the weight of the compound. can do. After completion of the reaction, for example, after recovering the solvent, the reaction product is extracted with an appropriate solvent, washed with water, dried, and concentrated to obtain the compound of formula (2) in high yield.
Can be obtained in high purity. Subsequently, the compound of formula (3) may be subjected to a deacetalization reaction in the presence of an acid catalyst, but if desired, it is also possible to use it after further purification by means such as vacuum distillation. . According to the method of the present invention, for example, the acetals of the formula (2) that can be obtained as described above are subjected to a deacetalization reaction in the presence of an acid catalyst.
The target aliphatic aldehyde (1) can be produced with good yield and purity. This deacetalization reaction can be carried out in water or an aqueous inert organic solvent. The reaction can be carried out in a wide temperature range, for example, from about -80°C to about +200°C, with a more preferred example being a temperature range from about -10°C to about 80°C. Although the reaction time can be changed as appropriate depending on the reaction temperature, the type of acid catalyst used, etc., for example, the reaction time can be about 1 hour to about 50 hours. Specific examples of acid catalysts used in the deacetalization reaction include mineral acids such as sulfuric acid, hydrochloric acid, and phosphoric acid; organic acids such as formic acid, acetic acid, and oxalic acid; and monochloroacetic acid, Examples include organic halogen acids such as trichloroacetic acid and trifluoroacetic acid. The amount of these acids used is, for example, about 0.0001 to 1 mole of the compound of formula (2) above.
About 0.1 mol is sufficient, but the amount used can be changed as appropriate depending on the type of acid catalyst. Specific examples of the solvent used in the above deacetalization reaction include water, or a mixture of water and a suitable organic solvent, such as a water-miscible solvent such as acetone, tetrahydrofurandioxane, dimethylformamide, dimethyl sulfoxide, and methanol. can be mentioned. There is no particular restriction on the amount of these solvents used, but the amount used is about 1 to about 200 times, more preferably about 5 to about 50 times the weight of the compound of formula (2). I can give an example. After the completion of the above reaction, for example, the reaction product is extracted with an appropriate solvent, the solvent layer is washed with water,
By drying and concentrating after neutralization, the aliphatic aldehyde represented by formula (1) can be obtained in high yield and purity. If desired, further purification can be carried out, for example, by means such as vacuum distillation or column chromatography. Hereinafter, several aspects of the present invention will be explained in more detail with reference to Examples. Example 1 Cis-6-nonenal From 12 g (0.1 mol) of cis-3-hexenyl chloride and 2.6 g (0.11 mol) of metallic magnesium, cis-6-nonenal was prepared in 70 ml of tetrahydrofuran.
Prepare 3-hexenylmagnesium chloride. Then, 2-(2-bromoethyl)-1.3-
Dioxolane 14.5g (0.08mol), Li ₂ CuCl ₄ 0.008
mol, in a mixed solution of tetrahydrofuran, −10 to
The Grignard reagent is added dropwise while cooling to maintain the temperature at 0°C. After the dropwise addition was completed, stirring was further continued for 2 hours at 0 to 30°C, and then the reaction was completed. The reaction solution was poured into 200 ml of ammonium chloride water, and the organic layer was extracted with 500 ml of ether. The mixture was washed twice with 200 ml of water, then dried over anhydrous magnesium sulfate, and the ether was recovered to obtain 13 g of crude 1,1-ethylenedioxy-cis-6-nonene. Distillation was performed under reduced pressure to obtain 12 g (82% yield) of 1,1-ethylenedioxy-cis-6-nonene having a boiling point of 80-82°C/2 mmHg. Next, the mixture was stirred overnight with 100 ml of 10% sulfuric acid water and 50 ml of tetrahydrofuran to perform a deacetal reaction. Extract the organic matter with 100ml of ether. After neutralizing with aqueous sodium bicarbonate and drying over anhydrous magnesium sulfate, the ether was recovered to obtain 9.1 g of crude cis-6-nonenal. Then, the mixture was distilled under reduced pressure to obtain 8.5 g (93% yield) of a cis-6-nonenal fraction having a boiling point of 65-68°C/2 mmHg. Similar reactions were carried out below, and the results shown in the table below were obtained.

【table】

Claims (1)

[Claims] 1 The following formula (3), [Formula] In the formula, R ² is a C ₁ to C ₅ alkyl group, a benzyl group, or two R ^2s taken together are (-CH ₂
) _-o (where n represents 2 or 3), X represents Br or I, and β-halopropanal acetals represented by the following formula (4), P ¹ MgY (4), where in the formula , R ¹ is a C ₁ to C ₂₀ alkyl group, C ₂ to
A Grignard reagent represented by the following represents a _C20 alkenyl group or a _C2 to _C20 alkynyl group, and Y represents a halogen atom, and is subjected to a coupling reaction in an inert organic solvent in the presence of a coupling catalyst to produce the following reaction. Formula (2), [Formula] However, in the formula, R ¹ and R ² have the same meaning as above, forming acetals represented by and deacetalizing the acetals in the presence of an acid catalyst. A method for producing aliphatic aldehydes represented by the following formula (1), R ¹ CH ₂ CH ₂ CHO (1) where R ¹ has the same meaning as above.