JPH0157103B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing an alicyclic compound. More specifically, the present invention relates to a method for producing a 1,2-divinylcyclopropane compound and/or an alicyclic seven-membered ring compound via Cope rearrangement of the divinylcyclopropane compound. Conventionally, the Cope rearrangement of 1,2-divinylcyclopropane-based compounds has been known as a seven-membered ring formation method, but it has the disadvantage that it is relatively difficult to synthesize the 1,2-divinylcyclopropane-based compounds themselves. , it was a reaction that was difficult to use from the viewpoint of organic synthesis [e.g. organic synthetic chemistry 34, 396
(1976); see 38, 381 (1980)]. The present inventors have conducted extensive studies on a method for producing a 7-membered ring compound via Cope rearrangement of a 1,2-divinylcyclopropane compound, including an easy means for producing the 1,2-divinylcyclopropane compound. The present invention has now been completed. That is, according to the present invention, the general formula () (In the formula, R ¹ and R ² are the same or different and represent a hydrogen atom, a lower alkyl group or a cycloalkyl group, R ³ represents a lower alkyl group, a lower alkoxy group or an aryl group, and R ¹ , R ² and R ³
Any two of them may be taken together to form a ring. ) and general formula () (In the formula, R ⁴ represents a hydrogen atom or a lower alkyl group, and Z ¹ and Z ² represent the same or different halogen atoms.) By condensing the compound represented by the general formula () in the presence of a base, (In the formula, R ¹ , R ² and R ³ are as defined above, and one of R ⁵ and R ⁶ is equal to R ⁴ above, and the other is a hydrogen atom.) and/or General formula () The compound represented by the formula (wherein R ¹ , R ² , R ³ , R ⁵ and R ⁶ are as defined above) can be easily produced. It has also been found that when the compound represented by the general formula () obtained in the above reaction is heated to about 150°C to about 250°C, it rearranges to the compound represented by the general formula (). The reaction mechanism in the method of the present invention can be depicted as follows. As described above, in accordance with the present invention, compound () and compound () are combined in the presence of a base from about 0°C to about 80°C.
When condensed in a range of (in situ) compound ()
Because compound (B) is difficult to take the transition state necessary for Cope rearrangement, it remains in the system as it is,
In the end, the final product of this reaction is compound (B) [corresponding to the compound represented by the general formula (). ] and the compound () are obtained. However, compound (B) is heated at a temperature of about 150°C to about 250°C, preferably about 170°C to about 200°C.
When heated to ℃, Cope rearrangement gradually progresses to form compound (). In the general formula (), R ¹ and R ² are each independently a hydrogen atom, a lower alkyl group (e.g., methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, t-butyl group, etc.) or a cyclo It can be an alkyl group (eg, cyclopentyl group, cyclohexyl group, etc.). In addition, R ³ is a methyl group, an ethyl group, an n-propyl group,
Lower alkyl groups such as isopropyl group, n-butyl group, t-butyl group, methoxy group, ethoxy group,
It can be a lower alkoxy group such as n-propoxy group or n-butoxy group, or an aryl group such as phenyl group, tolyl group or naphthyl group. Note that R ¹ , R ² and R ³ are any two of them.
may be joined together to form a ring. Preferred examples of the compound represented by the general formula () used in the present invention include mesityl oxide, cyclopentylidene acetone, cyclohexylidene acetone, 4-
Ethyl-3-hexen-2-one, isophorone,
Examples include 3-methyl-1-phenyl-2-buten-1-one and lower alkyl senethionate (eg, ethyl senethionate). In the general formula (), R ⁴ is a hydrogen atom or a lower alkyl group (e.g. methyl group, ethyl group, etc.)
and Z ¹ and Z ² can be the same or different halogen atoms, such as Cl or Br. Suitable examples of the compound represented by the general formula () include 1,4-dichloro-2-butene, 1,
4-dibrome-2-butene, 1,4-dibrome-
Examples include 2-methyl-2-butene. In the condensation reaction according to the present invention, alkali metal amides such as lithium amide and sodium amide, potassium t-butoxide and other alkali metal alkoxides, etc. can be used as bases, but for mass production, sodium hydroxide, water It is particularly preferred to use a combination of an aqueous solution of an alkali metal hydroxide, such as potassium oxide, and a phase transfer catalyst. The concentration of the alkali metal hydroxide in the aqueous alkali metal hydroxide solution is about 30% by weight or more, preferably within the range of about 40% to 65% by weight. The amount of the alkali metal hydroxide aqueous solution to be used is such that the molar ratio of the alkali metal hydroxide to the compound represented by the general formula () is about 2 to 20, preferably about 3 to 8.
It is best to choose one that falls within the range of . As the phase transfer catalyst, it is preferable to use quaternary ammonium salts, phosphonium salts, etc., and specific examples of particularly recommended catalysts include tetrabutylammonium chloride, tetrabutylammonium bisulfate, tetrabutylammonium iodide, and trimethylbenzylammonium chloride. , trimethyllauryl ammonium chloride, trimethylcetylammonium chloride, trimethylstearylammonium chloride, trimethylstearylammonium bromide, dimethyldicyclohexylphosphonium chloride, methyltricyclohexylphosphonium chloride, ethyltricyclohexylphosphonium chloride, ethyltricyclohexylphosphonium bromide, and the like. The amount of phase transfer catalyst used is about 0.1 mol% to about 10 mol% based on the compound represented by the general formula ()
The range up to is preferred. A compound represented by the general formula () is expressed by the general formula ()
It is preferable to use the compound at a molar ratio of about 2 to 6 times that of the compound represented by. Suitable reaction temperatures vary widely depending on the type of base used, with temperatures around 20
Particularly preferred are temperatures within the range of 80°C to about 80°C. Although the use of a reaction solvent is not particularly necessary, it may be used as long as it is stable under the reaction conditions. The rearrangement reaction from the compound represented by the general formula () to the compound represented by the general formula () is carried out at the above temperature, that is, about 150°C to about 250°C, preferably about 170°C to about 200°C.
The reaction can be carried out at a temperature of 100 ml without a solvent or in the presence of an aromatic hydrocarbon solvent such as paracymene or mesitylene or another suitable solvent. This rearrangement reaction is preferably carried out under an atmosphere of nitrogen gas or other inert gas. The compound represented by the general formula () produced by the method of the present invention is useful, for example, as a fragrance or an antibacterial agent, or as a synthetic raw material for fragrances, medicines, antibacterial agents, etc. It can be used as a raw material for the synthesis of compounds shown in parentheses and other useful compounds. The present invention will be explained below using examples. Example 1 Mesityl oxide 5.0g (50.9mmol), trans-1,4-dichloro-2-butene 6.25g
(50.0 mmol), trimethylstearylammonium chloride 0.70 g (2.0 mmol) and benzene 5
ml of the mixed solution was added an aqueous sodium hydroxide solution (8 g of NaOH in 10 ml of water) and stirred at 20°C for 30 minutes, then the temperature was raised to 50°C in 15 minutes, and stirring was continued at 50°C for an additional 2.5 hours. . The reaction solution was then poured into water and extracted with diethyl ether. The resulting ether layer was washed with saturated brine and dried over magnesium sulfate. The solvent and unreacted mesityl oxide were distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 1-acetyl-2-methyl-1,5-cycloheptadiene (i) and 1-acetyl -1-vinyl-2-isopropenylcyclopropane (ii) at 18.1% and
6.6% yield (based on reacted mesityl oxide)
I got it from The structures of these products were confirmed based on the following analysis results.

【formula】

[Formula] Infrared absorption spectrum (neat): 1680, 1618, 1433, 1351, 1270, 1190, 630cm
^-1 nuclear magnetic resonance spectrum δ ^{in CDc3} _ppn : 1.92 (s, 3H), 2.20-2.30 (m, 2H), 2.15 (s,
3H), 2.30-2.58 (m, 2H), 3.03 (br.s, 2H),
5.53 (AB, 2H) Nuclear magnetic resonance spectrum δ ^{in CDc3} _ppn : 0.96 (dd, J = 8.7, 3.9Hz, 1H), 1.65 (dd, J
=6.3, 3.9Hz, 1H), 1.83 (s, 3H), 1.95~
2.35 (m, 1H), 2.20 (s, 3H), 4.90~5.80 (m,
3H), 5.12 (s, 2H) Example 2 3-methyl-1-phenyl-2-butene-1-
8.15 g (50.9 mmol), trans-1,4-dichloro-2-butene 6.25 g (50.0 mmol), tetra n-butylammonium bisulfate [(n-
_{Aqueous sodium} hydroxide solution _{( water}
(contains 8g of NaOH in 10ml) and incubate at 20℃ for 30 minutes.
After stirring for 15 minutes, the temperature was increased to 50℃, and then the temperature was increased to 50℃.
Stirring was continued for an additional 3 hours. After the reaction, the reaction solution was treated in the same manner as in Example 1 to obtain 1-benzoyl-2-methyl-1,5-cyclohebutadiene.
(iii) and 1-benzoyl-1-vinyl-2-isopropenylcyclopropane (iv) with yields of 25.4% and 6.3%, respectively (based on 3-methyl-1-phenyl-2-buten-1-one charge). I got it from The structures of these products were confirmed based on the following analysis results.

【formula】

[Formula] Nuclear magnetic resonance spectrum δ ^{in CDc3} _ppn : 1.63 (s, 3H), 2.07-2.58 (m, 4H), 2.93 (br.
s, 2H), 5.58 (AB, 2H), 7.20~7.50 (m,
3H), 7.75-7.95 (m, 3H) Nuclear magnetic resonance spectrum δ ^{in CDc3} _ppn : 0.95 (dd, J=9.1, 4.8Hz, 1H), 1.63 (s,
3H), 1.78 (dd, J=7.2, 4.8Hz, 1H), 2.33~
2.60 (m, 1H), 4.73~5.33 (m, 5H), 7.20~
7.50 (m, 3H), 7.75-7.96 (m, 2H) Example 3 Isophorone 7.03g (50.9mmol), trans-
1,4-dichloro-2-butene 6.25g
(50.0 mmol), tetra n-butylammonium iodide [(n-C ₄ H ₉ ) ₄ NI] 0.74 g
(2.0 mmol) and benzene (5 ml) was added with an aqueous sodium hydroxide solution (containing 8 g of NaOH in 10 ml of water), stirred at 15°C for 30 minutes, heated to 50°C over 20 minutes, and further heated at 50°C. Stirring was continued for 3 hours. After the reaction, the reaction solution was treated in the same manner as in Example 1 to obtain compounds represented by the following formulas (v) and (vi) in yields of 6.7% and 13.4%, respectively (based on the reacted isophorone).

【formula】

[Formula] Infrared absorption spectrum (neat): 1665, 1640, 1380, 1370, 1300, 1280, 900cm
^-1 nuclear magnetic resonance spectrum δ ^{in CDc3} _ppn : 1.00 (s, 6H), 1.90~2.37 (m, 6H), 2.37~
2.65 (m, 2H), 3.08 (br.s, 2H), 5.53 (AB,
2H) Nuclear magnetic resonance spectrum δ ^{in CDc3} _ppn : trans-(vi); 1.02 (s, 3H), 1.08 (s, 3H), 1.38 (dd, J=
8.5, 4.3Hz, 1H), 1.55 (s, 3H), 1.70~2.12
(m, 2H), 2.23 (s, 2H), 4.93 (dd, J=7.3,
2.3Hz, 1H), 5.11 (dd, J=15.3, 2.3Hz, 1H),
5.38-5.88 (m, 1H), 5.57 (s, 1H) cis-(vi); 1.03 (s, 3H), 1.12 (s, 3H), 1.26 (dd, J=
6.7, 3.8Hz, 1H), 1.61 (s, 3H), 1.75~2.13
(m, 2H), 2.23 (s, 2H), 5.07 (dd, J=9.4,
2.9Hz, 1H), 5.21(dd, J=13.7, 2.88Hz,
1H), 5.35-5.83 (m, 1H), 5.73 (s, 1H) Example 4 5.0 g of a 2:3 mixture of cyclopentylidene acetone and 1-cyclopentenyl acetone
(40.3mmol), trans-1,4-dichlor-2
- Adding an aqueous sodium hydroxide solution (8 g of NaOH in 10 ml of water) to a mixture of 5.0 g (40.0 mmol) of butene, 0.74 g (2.0 mmol) of tetra-n-butylammonium iodide, and 5 ml of benzene.
After stirring at 16°C for 30 minutes, the temperature was raised to 50°C over 15 minutes, and stirring was continued at 50°C for an additional 3 hours. After the reaction,
By treating the reaction solution in the same manner as in Example 1, the compounds represented by the following formulas (vii) and (viii) were each converted to 8
%
and a yield of 12% (based on the ketone starting material).

【formula】

[Formula] Nuclear magnetic resonance spectrum δ ^{in CDc3} _ppn : 1.57-1.92 (m, 4H), 1.92-2.54 (m, 2H),
2.18 (s, 3H), 2.54-2.93 (m, 3H), 3.08
(AB, 2H), 5.47 (AB, 2H) Nuclear magnetic resonance spectrum δ ^{in CDc3} _ppn : 0.92 (dd, J = 9.0, 4.4Hz, 1H), 1.63 (dd, J
=7.2, 4.4Hz, 1H), 1.81~2.23 (m, 3H),
2.07 (s, 3H), 2.23~2.56 (m, 4H) 4.97~
5.65 (m, 3H), 5.72 (t, J = 1.8Hz, 1H) Example 5 Mesityl oxide 147g (1.5mol), trans-1,4-dichloro-2-butene 62g (0.5mol)
Add 88 g of a 50% by weight aqueous sodium hydroxide solution to a mixture of 1 g of trimethylstearylammonium chloride and 1 g of trimethylstearylammonium chloride while stirring at 45°C.
(NaOH 1.1 mol) was added dropwise, and stirring was continued at the same temperature for an additional 4 hours. The reaction solution was then poured into water and extracted with diethyl ether. The resulting ether layer was washed with saturated brine and dried over magnesium sulfate. The solvent and unreacted mesityl oxide were distilled off under reduced pressure, and the residue was vacuum distilled to a boiling point of 52-56℃/
22.5 g of 1-acetyl-2-methyl-1,5-cycloheptadiene as a 0.3 mmHg fraction (yield 30
%) was obtained. Example 6 Example 5 except that 207 g (1.5 mol) of isophorone was used instead of mesityl oxide (1.5 mol).
The reaction and post-treatment were carried out in the same manner as in Example 3.
38 g (yield: 40%) of the compound represented by formula (v) was obtained. Example 7 1-Acetyl-1-vinyl-2 is produced by reacting mesityl oxide and trans-1,4-dichloro-2-butene according to the method of Example 1.
-Synthesized isopropenylcyclopropane. 50 mg of this 1-acetyl-1-vinyl-2-isopropenylcyclopropane was dissolved in 3 ml of paracymene, and after reaction at 170°C for 24 hours in a nitrogen gas atmosphere, the product was purified by silica gel column chromatography. 45 mg of acetyl-2-methyl-1,5-cycloheptadiene was obtained. Example 8 3-Methyl-1-phenyl-2-buten-1-one and trans-1,4 according to the method of Example 2
1-benzoyl-1-vinyl-2-isopropenylcyclopropane was synthesized by reacting it with -dichloro-2-butene. 100 mg of this 1-benzoyl-1-vinyl-2-isopropenylcyclopropane was dissolved in 5 ml of mesitylene and subjected to a rearrangement reaction at 190°C for 15 hours in a nitrogen gas atmosphere.
83 mg of benzoyl-2-methyl 1,5-cycloheptadiene was obtained. Example 9 Ethyl 3-methylcrotonate 5.12g (40mmol)
and trans-1,4-dibromo-2-butene
Dissolve 8.4g (40mmol) in 100ml of tetrahydrofuran and add 8.96g (8.96g) of tert-butoxypotassium powder to this.
After slowly adding 40 g (80 mmol) at room temperature,
The reaction was carried out at ℃ for 3 hours. The solvent was then distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 1-ethoxycarbonyl-2-methyl 1,5-cycloheptadiene.
1.8g (yield 25%) was obtained. Example 10 In the same manner as in Example 1, 5-cyclohexyl-4
- 4 g of NaOH in a mixed solution of 5.24 g (20 mmol) of cyclohexylmethyl-3-penten-2-one, 2.48 g (20 mmol) of trans-1,4-dichloro-2-butene, 0.1 g of trimethylstearylammonium chloride, and 10 ml of benzene. A 5 ml solution of water was added, and the reaction was carried out at 50°C for 3 hours. The product was purified by silica gel column chromatography to obtain 1.76 g (yield 28%) of 1-acetyl-2-cyclohexylmethyl-3-cyclohexyl-1,5-cycloheptadiene.

Claims (1)

[Claims] 1. General formula (In the formula, R ¹ and R ² are the same or different and represent a hydrogen atom, a lower alkyl group or a cycloalkyl group, R ³ represents a lower alkyl group, a lower alkoxy group or an aryl group, and R ¹ , R ² and R ³
Any two of them may be taken together to form a ring. ) and the general formula (In the formula, R ⁴ represents a hydrogen atom or a lower alkyl group, and Z ¹ and Z ² represent the same or different halogen atoms.) A general formula characterized by condensing a compound represented by the following in the presence of a base: (In the formula, R ¹ , R ² and R ³ are as defined above, and R ⁵ and R ⁶ are either one of the above R ⁴
and the other is a hydrogen atom. ) Compounds and/or general formulas represented by (In the formula, R ¹ , R ² , R ³ , R ⁵ and R ⁶ are as defined above.) A method for producing a compound represented by the following. 2 General formula (In the formula, R ¹ and R ² are the same or different and represent a hydrogen atom, a lower alkyl group or a cycloalkyl group, R ³ represents a lower alkyl group, a lower alkoxy group or an aryl group, and R ¹ , R ² and R ³
Any two of them may be taken together to form a ring. ) and the general formula (In the formula, R ⁴ represents a hydrogen atom or a lower alkyl group, and Z ¹ and Z ² represent the same or different halogen atoms.) The general formula obtained by condensing the compound represented by the following in the presence of a base: (In the formula, R ¹ , R ² and R ³ are as defined above, and R ⁵ and R ⁶ are either one of the above R ⁴
and the other is a hydrogen atom. ) A general formula characterized by rearrangement by heating the compound represented by about 150°C to about 250°C (In the formula, R ¹ , R ² , R ³ , R ⁵ and R ⁶ are as defined above.) A method for producing a compound represented by the following.