JPH027300B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula () The present invention relates to a method for producing a δ,ε-unsaturated carbonyl compound represented by: In the above general formula (), R ¹ , R ² , R ³ , R ⁴
and R ⁵ are the same or different, each being a hydrogen atom; methyl, ethyl, propyl, butyl, 3-methylbutyl, pentyl, hexyl, heptyl, octyl, 3,7-dimethyloctyl, etc. Alkyl group; cycloalkyl group such as cyclopentyl group, cyclohexyl group, menthyl group;
Vinyl group, 1-propenyl group, allyl group, isopropenyl group, 2-methylallyl group, 1-butenyl group, 2-butenyl group, prenyl group, 3-methyl-
3-butenyl group, 2,3-dimethyl-2-butenyl group, 3-methyl-2-pentenyl group, 3-methyl-3-pentenyl group, 3,7-dimethyl-2-
Octenyl group, 3,7-dimethyl-6-octenyl group, geranyl group, neryl group, 3-ethyl-7-
Alkenyl groups such as methyl-2,6-nonadienyl; alkynyl groups such as propargyl, 2-butynyl, and 3-butynyl; aryl groups such as phenyl, tolyl, xylyl, and naphthyl; or benzyl, 1-phenylethyl group, 2
-phenylethyl group, 1-phenylpropyl group,
It represents an aralkyl group such as a 3-phenylpropyl group, a 2-methyl-1-phenylpropyl group, or a 2-naphthylethyl group. Further, R ⁴ and R ⁵ may be combined with the carbon atoms to which they are bonded to form a ring. The δ,ε-unsaturated carbonyl compound represented by the general formula () can not only be used as a fragrance per se, but is also a compound useful as an intermediate in the production of fragrances, cosmetic base materials, medicines, agricultural chemicals, and the like. Conventionally, δ, ε-unsaturated ketones are produced by reacting mesityl oxide with halogenated hydrocarbons in the presence of an alkaline condensing agent to form β, γ-unsaturated ketones with α-positions substituted with hydrocarbon groups. It is produced by reacting with a vinyl Grignard reagent or ethynylation reaction followed by partial hydrogenation to obtain an allyl type alcohol, and then heating and isomerizing the allyl type alcohol (JP-A-52-1999)
83409). This conventional method is excellent as an industrial method for producing δ,ε-unsaturated ketones because it uses cheap mesityl oxide as a raw material and is easy to operate. The δ,ε-unsaturated ketones produced by this method are limited to those having a methyl group at the δ position of the basic skeleton and one hydrocarbon group at the ε position, and are therefore diverse. It is not suitable for the production of δ,ε-unsaturated ketones. The present inventors have made extensive studies to solve the above-mentioned problems in the conventional method using mesityl oxide as a raw material. The present inventors have discovered a method for producing the same, leading to the present invention. That is, according to the present invention, the general formula () [In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are general formula ()
has the same meaning as in and R ⁶ represents an alkyl group or an aryl group. ] A δ,ε-unsaturated carbonyl compound represented by the general formula () can be produced by oxidizing the sulfur-containing homoallylic alcohol represented by the formula to form the corresponding sulfoxide, and then reacting the sulfoxide under heating. can. In addition, the sulfur-containing homoallylic alcohol represented by the general formula () has the general formula () [In the formula, R ¹ , R ² and R ³ have the same meanings as in the general formula (), and X represents a chlorine atom, a bromine atom or an iodine atom. ] Allyl Grignard reagent and general formula () [In the formula, R ⁴ , R ⁵ and R ⁶ have the same meanings as in the general formula (). ] It can be obtained in high yield by reacting with the β-thiocarbonyl compound shown below. The corresponding sulfoxide can be obtained by oxidizing the sulfur-containing homoallylic alcohol represented by the general formula (). This oxidation reaction can be carried out according to ordinary oxidation methods, including performic acid, peracetic acid, perpropionic acid, perphthalic acid, perbenzoic acid,
This can be easily carried out by a method known per se, which involves treatment with an organic peracid such as m-chloroperbenzoic acid or a suitable oxidizing agent such as hydrogen peroxide. As the oxidizing agent, m-chloroperbenzoic acid is particularly preferred from the viewpoint of ease of handling and selectivity to the target sulfoxide.
[D. Heissler, Tetrahedron Letters 4879 (1976)
reference〕. The optimal amount of the oxidizing agent to be used is about 1 equivalent relative to the sulfur-containing homoallylic alcohol. The reaction temperature is suitably in the range of -30°C to +50°C. Further, this oxidation reaction is preferably carried out in the presence of a solvent, and inert solvents such as chloroform, methylene chloride, carbon tetrachloride, benzene, and toluene are used as the solvent. After the reaction is completed, the organic acid produced from the reaction mixture and the unreacted oxidizing agent are neutralized with a base and then removed, and then the solvent is distilled off to obtain a sulfoxide. This sulfoxide can then be subjected to a reaction under heat without purification. In a preferred embodiment when m-chloroperbenzoic acid is used as the oxidizing agent, a sulfur-containing homoallylic alcohol represented by the general formula () is added to a methylene chloride solution in which the sulfur-containing homoallylic alcohol is dissolved. The reaction is carried out by adding approximately 1 equivalent of a methylene chloride solution of m-chloroperbenzoic acid dropwise at 0 to 5°C, followed by stirring at room temperature for about 1 hour. After the reaction was completed, a 10% potassium hydroxide aqueous solution was added to the reaction mixture in an amount of about 3 times the molar amount of the m-chloroperbenzoic acid used, and the m-chloroperbenzoic acid used was added.
- Neutralize chlorobenzoic acid and unreacted m-chloroperbenzoic acid. Next, wash this mixed solution with water,
After drying, methylene chloride is distilled off from this under reduced pressure, and the resulting residue containing sulfoxide is subjected to the next reaction under heating. A δ,ε-unsaturated carbonyl compound represented by the general formula () is obtained by reacting the sulfoxide corresponding to the sulfur-containing homoallylic alcohol represented by the general formula () obtained by the above oxidation reaction under heating. be able to. This reaction can be carried out in liquid phase or gas phase by heating at a temperature of about 100 to 600°C, but from the viewpoint of reaction rate and selectivity, the temperature is about 130 to 250°C, preferably 150 to 230°C.
It is practical to carry out the process in the liquid phase. Although there are no particular restrictions on the atmosphere of the reaction system, an atmosphere of an inert gas such as nitrogen or helium is generally preferred. Although this reaction can be carried out in the absence of a solvent, it is preferably carried out in the presence of a solvent. As a solvent, N,N-dimethylformamide, ε-caprolactam, N-methyl-2-pyrrolidone, N-
Nitrogen-containing compounds such as ethyl-2-pyrrolidone are particularly preferably used. The reaction time is greatly influenced by the reaction temperature, but when the reaction is carried out at a temperature of 165° C. in a liquid phase system using N-methyl-2-pyrrolidone as a solvent, the reaction is completed in about 6 hours. This reaction under heating is thought to proceed through a two-step reaction as shown in the following formula, but the reaction mechanism is not particularly limited. After the reaction is complete, in the case of a reaction mixture obtained in the absence of a solvent, it can be directly distilled, or in the case of a reaction mixture obtained in the presence of a solvent, it can be poured into water and diluted with, for example, hexane. The δ,ε-unsaturated carbonyl compound represented by the general formula () can be isolated by distilling the extract or subjecting it to column chromatography. The allyl Grignard reagent represented by the general formula () is prepared by mixing the corresponding allyl halide and magnesium metal in an ether solvent such as tetrahydrofuran or diethyl ether in an atmosphere of an inert gas such as nitrogen or helium at -30°C to 50°C. It can be prepared by reacting at a temperature of preferably -5°C to 30°C. The time required for this reaction is considerably influenced by the type of allyl halide and the reaction temperature, but is usually about 1 hour. A β-thiocarbonyl compound represented by the general formula () is added dropwise to this reaction system at a temperature of -30°C to 50°C, preferably -10°C to 30°C, and the mixture is stirred for about 1 hour at that temperature or at room temperature. A reaction mixture containing a sulfur-containing homoallylic alcohol represented by the general formula () is obtained. The amount of the β-thiocarbonyl compound represented by the general formula () is approximately 0.3 to 0.3 to the allyl Grignard reagent represented by the general formula ().
1 equivalent, preferably about 0.5 to 0.9 equivalent. The sulfur-containing homoallylic alcohol can be separated and recovered from the reaction mixture by a conventional method. For example, an ammonium chloride aqueous solution is added to the reaction mixture, followed by extraction with diethyl ether, hexane, etc., the extract is washed with water, dried, and the solvent is distilled off to obtain the sulfur-containing homoallylic alcohol represented by the general formula (). obtain. This sulfur-containing homoallylic alcohol can be subjected to the next oxidation reaction without being purified, but there is no problem in subjecting a sulfur-containing homoallylic alcohol that has been further purified by distillation or column chromatography to the oxidation reaction. do not have. β- represented by the general formula () used as a raw material
Thiocarbonyl compounds have the general formula () [In the formula, R ⁴ and R ⁵ have the same meanings as in the general formula (). ] An α,β-unsaturated carbonyl compound represented by the general formula () R ⁶ SH ... () [wherein R ⁶ has the same meaning as in the general formula (). ] The thiol represented by 1,5-diazabicyclo[5,4,0]undecene-5 (commonly known as DBU), 1,
It can be easily produced by reaction in the presence of an organic nitrogen base such as 4-diazabicyclo[2,2,2]octane (commonly known as DABCO).
Examples of the α,β-unsaturated carbonyl compound represented by the general formula () include methyl vinyl ketone,
Examples include ethyl vinyl ketone, methyl isopropenyl ketone, and isobutenyl aldehyde. Preferred examples of the thiol represented by the general formula () include methanethiol, ethanethiol, and benzenethiol. Hereinafter, the present invention will be specifically explained with reference to Examples. Example 1 1-(2-ethylthio)ethyl-1,2,2-
Synthesis of trimethyl-3-buten-1-ol Magnesium metal in a 100ml three-necked flask
0.32 g and 30 ml of dry tetrahydrofuran were taken, and 1.37 g of prenyl chloride was gradually added dropwise under a nitrogen gas stream while keeping the internal temperature at 20 to 25°C to prepare a Grignard reagent. Next, add 4 to this Grignard reagent.
-Ethylthio-2-butanone (94% purity) 1.40g
5 ml of tetrahydrofuran solution was added dropwise at an internal temperature of 20 to 23°C. After stirring for 1 hour at room temperature, the reaction mixture was poured into a large amount of aqueous ammonium chloride solution.
This was extracted with diethyl ether. The extract was washed several times with water and then dried over anhydrous sodium sulfate. After distilling off the ether under reduced pressure, the residue was subjected to silica gel column chromatography (eluent: ethyl acetate/hexane mixed solution, volume ratio 1/
10), 1.91g of oily substance (purity 98
%) was obtained. Yield 93%. This product was confirmed to be 1-(2-ethylthio)ethyl-1,2,2-trimethyl-3-buten-1-ol by H1 ^- NMR and IR analysis. Representative signals are listed below. H ¹ −NMR (CDCl ₃ , ppm) 1.00 (6H, s)

【formula】 1.10 (3H, s)

【formula】 1.20 (3H, t)

【formula】 1.50~1.92 (2H, m)

【formula】 2.34~2.78 (4H, m)

[Formula] 4.87-5.18 (2H, m) = CH ₂ 5.80-6.20 (1H, m) - CH = IR (cm ^-1 ) 3480, 3080, 2960, 2920, 2880,
1635, 1450, 1420, 1375, 1275, 1110, 1010,
920, 790 Synthesis of 7-methyl-6-octen-2-one 1-(2-ethylthio)ethyl-1,2,2-
0.51 g of trimethyl-3-buten-1-ol was dissolved in 5 ml of methylene chloride and cooled to about 0°C. Next, m-chloroperbenzoic acid (purity 80
%) in 20 ml of methylene chloride was added dropwise at the same temperature. Then, the temperature was returned to room temperature and stirred for 1 hour. A 10% aqueous sodium hydroxide solution in an amount of three times the amount of m-chloroperbenzoic acid used was added to the reaction mixture, and the mixture was stirred for 1 hour. The methylene chloride layer was separated, and the aqueous layer was further extracted with methylene chloride. The methylene chloride layer and the methylene chloride extract were combined, and the mixed solution was washed with water and then dried over anhydrous sodium sulfate. Methylene chloride was distilled off under reduced pressure. The residue was dissolved in 2 g of N-methyl-2-pyrrolidone and heated under a nitrogen atmosphere at a bath temperature of 175±2° C. for 6 hours. The reaction mixture was then poured into a large amount of water and extracted with hexane. The hexane layer was washed with water and dried over anhydrous sodium sulfate. After distilling off hexane under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate-hexane system) to obtain 0.18 g of oily 7-methyl-6-octen-2-one. Obtained. Yield 51%. Characteristic fragments in the GC-MASS spectrum of the product are shown below. GC conditions: Column packing material PEG20M, column length 2
m, temperature 120℃ MASS spectrum m/e: [M] ⁺ 140, 122, 82,
67, 47 Examples 2 to 6 Various allyl Grignard reagents () and β-thiocarbonyl compounds () were reacted under the same conditions as in Example 1, and sulfur-containing homoallylic alcohols () were obtained by separation and recovery. Then, the sulfur-containing homoallylic alcohol () was prepared in Example 1
The δ,ε-unsaturated carbonyl compound () is obtained by heating the reaction under the same conditions and separating and purifying it
I got it. The results are shown in Table 1.

【table】

[Table] Examples 7 to 10 Various allyl Grignard reagents () and β-thiocarbonyl compounds () were reacted under the same conditions as in Example 1, and sulfur-containing homoallylic alcohols () were obtained by separation and recovery. Then, the sulfur-containing homoallylic alcohol () was subjected to a heating reaction under the same conditions as in Example 1 except that it was heated at 200°C, and the δ,ε-unsaturated carbonyl compound () was obtained by separation and purification. . The results are shown in Table 2.

【table】

【table】

Claims (1)

[Claims] 1. General formula (In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group, and R ⁴ and R ⁵ may form a ring together with the carbon atom to which they are bonded. R ⁶ represents an alkyl group or an aryl group. to form the corresponding sulfoxide, and then the sulfoxide is reacted under heating. (In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined above.) A method for producing a δ,ε-unsaturated carbonyl compound. 2 General formula (In the formula, R ¹ , R ² and R ³ are the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group or an aralkyl group, and X is a chlorine atom, a bromine atom or represents an iodine atom.) Allyl Grignard reagent and general formula represented by (In the formula, R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, or an aralkyl group, and R ⁴ and R ⁵ are the bonds between them. may form a ring together with the carbon atoms represented by the formula (R ⁶ represents an alkyl group or an aryl group). (In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are as defined above.) Obtaining a sulfur-containing homoallylic alcohol,
A general formula characterized in that the sulfur-containing homoallylic alcohol is oxidized to the corresponding sulfoxide, and then the sulfoxide is reacted under heating. (In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined above.) A method for producing a δ,ε-unsaturated carbonyl compound.