JPH06305984A - Production of cyclohexene derivative - Google Patents

Abstract

PURPOSE:To obtain the derivative industrially and advantageously with a recoverable and reusable catalyst by using the catalyst comprising a salt of a rare earth element and a perfluoroalkanesulfonate, reacting a conjugated olefin with an active olefin. CONSTITUTION:A conjugated olefin of formula II (R1 to R6 are H, alkyl, alkenyl, aryl, alkoxy or any two of R1 to R6 are linked to form cyclic structure) is reacted with an active olefin of formula III (R7 to R10 are H, halogen, alkyl, aryl, alkoxy, etc., or any two of R7 to R10 are linked to form cyclic structure) in the presence of a rare earth element-based catalyst of formula I (RE is rare earth element; Rf is perfluoroalkyl) as a catalyst to inexpensively give the objective cyclohexene derivative of formula IV in a shortened reaction time.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing a cyclohexene derivative useful as a synthetic intermediate for pharmaceuticals, agricultural chemicals and the like.

[0002]

2. Description of the Related Art As a method for producing a cyclohexene derivative, a so-called Diels-Alder reaction is known in which a compound having a conjugated double bond is reacted with a compound having an active double bond. At this time, the addition of a Lewis acid catalyst such as aluminum chloride makes it possible to proceed the reaction smoothly [J. Am. Chem. Soc., Vol. 82, p4432 (19
60); J. Org. Chem., Vol. 32, p869 (1967)].

However, when these Lewis acids are used, the reaction mixture is usually treated with water in order to separate the product from the Lewis acid after completion of the reaction. That is,
The Lewis acid catalyst is separated by reacting it with water to convert it into a water-soluble substance. However, it is very difficult to regenerate the Lewis acid catalyst from this water-soluble substance, and the treatment cost is high even when it is discarded, which is a problem as a method for industrially mass-producing. .

[0004]

Therefore, as a result of intensive studies to solve the above-mentioned problems, the inventors of the present invention have found that the Diels
When producing a cyclohexene derivative by the Alder reaction, it was found that the rare earth catalyst becomes a good catalyst, and by using this rare earth catalyst as a reaction catalyst, the catalyst recovery after the reaction is easy, Moreover, they have found that the recovered catalyst can be reused and have reached the present invention.

Therefore, an object of the present invention is to provide a method for industrially advantageous production of a cyclohexene derivative in which the catalyst can be easily recovered after completion of the reaction, and the recovered catalyst can be reused if necessary. To provide.

[0006]

That is, the present invention provides the following general formula (1):

[0007]

[Chemical 4]

(However, in the formula, R₁, R₂, R₃, R_Four,
R_FiveAnd R₆Is a hydrogen atom, an alkyl group, an alkenyl group,
An aryl group or an alkoxyl group, and R
₁, R ₂, R₃, R_Four, R_FiveAnd R₆Either two are one
May form a part of the ring structure)
Conjugated olefin and the following general formula (2)

[0009]

[Chemical 5]

(In the formula, R ₇ , R ₈ , R ₉ and R ₁₀
Is a hydrogen atom, halogen atom, alkyl group, alkenyl group, aryl group, alkoxyl group, acyloxy group, oxycarbonyl group, amino group, nitro group, cyano group, sulfonyl group, haloformyl group, formyl group, carboxyl group, carbamoyl group or It is an amidino group, and any two of R ₇ , R ₈ , R ₉ and R ₁₀ may be integrated to form a part of a cyclic structure. However, R ₇ , R
_At least one of ₈ , R ₉ and R ₁₀ is an alkenyl group, aryl group, alkoxyl group, acyloxy group, oxycarbonyl group, amino group, halogen atom, nitro group, cyano group, sulfonyl group, haloformyl group, formyl group. , A carboxyl group, a carbamoyl group or an amidino group) is reacted with an active olefin represented by the following general formula (3)

[0011]

[Chemical 6]

(However, in the formula, R₁, R₂, R₃, R_Four,
R_Five, R₆, R₇, R₈, R₉And R _TenIs the same as above
A method for producing a cyclohexene derivative represented by
In the following general formula (4) RE (OSO₂Rf)₃ (4) (where RE is a rare earth metal element and Rf is a
Rare-earth catalyst represented by a fluoroalkyl group)
For producing cyclohexene derivative by reacting in the presence of
Is.

Further, the present invention is the above-mentioned method for producing a cyclohexene derivative, which is a method in which after the reaction is completed, the rare earth catalyst used as the catalyst is recovered and the recovered catalyst is reused as the reaction catalyst.

In the above general formula (1), R ₁ , R ₂ ,
Examples of the alkyl group used as R ₃ , R ₄ , R ₅ and R ₆ include a substituted or unsubstituted methyl group, ethyl group, propyl group, butyl group, isobutyl group, t-butyl group, octyl group and dodecyl group. Can be widely illustrated.
Examples of the alkenyl group used as R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ include a substituted or unsubstituted ethenyl group, propenyl group, butenyl group and the like. Further, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆
Examples of the aryl group used as are a substituted or unsubstituted phenyl group, tolyl group, naphthyl group, pyridyl group, thienyl group, furyl group, pyrrolyl group and the like. Specific examples of the alkoxyl group used as R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ include a methoxyl group, an ethoxyl group and a butoxyl group.

The halogen elements used as R ₇ , R ₈ , R ₉ and R ₁₀ in the above general formulas (2) and (3) include chlorine, bromine and iodine. Further, examples of the acyl group used as R ₇ , R ₈ , R ₉ and R ₁₀ include an acetyl group, a propionyl group, a butyryl group, an acryloyl group, a propioloyl group, a benzoyl group, a naphthoyl group and a nicotinoyl group. it can.

In the above general formulas (1) and (3), any _{two of} R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are integrated to form a part of the ring structure. R may be formed, and in the above general formulas (2) and (3), R
Any two of ₇ , R ₈ , R ₉ and R ₁₀ may together form a part of a cyclic structure. Specific examples of the cyclic structure include a cyclohexane ring, a cyclohexene ring and a cyclopentane ring. And a cycloalkane ring such as a cyclopentene ring or a cycloalkene ring.

Further, in the above general formula (4), as RE, scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, etc. Rare earth elements can be preferably used.
As for the rare earth element RE, only one kind thereof may be used alone, or a mixture of two or more kinds may be used. Examples of Rf include perfluoroalkyl groups such as trifluoromethyl group, pentafluoroethyl group, nonafluorobutyl group and the like.

In carrying out the reaction of the present invention, the conjugated olefin and the active olefin are usually used in stoichiometric amounts, that is, equimolar amounts, but either one may be used in excess. In particular, when one of the compounds is inexpensive, it is preferable to use it in excess, because the reaction can be speeded up.

The amount of the rare earth catalyst used in the reaction of the present invention is 0.01 to 200 mol%, preferably 0.1 to 200 mol% with respect to the compound of the conjugated olefin and the active olefin, which has a small amount of use. It is 100 mol%. 0.
If the amount used is less than 01 mol%, the reaction is slow and the reaction does not substantially proceed. On the other hand, the rare earth-based catalyst may be used in a large amount exceeding the above range, but there is no economic advantage because the reaction rate is not substantially improved.

The reaction of the present invention can be carried out without a solvent, but a solvent may be used. As the solvent, dichloromethane, chloroform, dichloroethane, halogenated hydrocarbon represented by chlorobenzene, hexane,
Aliphatic or alicyclic hydrocarbons such as cyclohexane, aromatic hydrocarbons such as benzene and toluene, aprotic solvents such as acetonitrile, nitromethane, nitrobenzene and carbon disulfide, or water. Although a wide range of protic solvents such as methanol, ethanol, and isopropanol can be used, halogenated hydrocarbons, acetonitrile, nitromethane, carbon disulfide, water and the like are preferable from the viewpoint of high solubility of raw materials and catalysts. Moreover, it does not interfere even if these mixed solvents are used.

The reaction temperature will differ depending on the reaction solvent and catalyst used, but will usually be in the range of -100 ° C to 300 ° C, and preferably in the range of room temperature to 200 ° C. Also,
The reaction time also varies depending on the reaction conditions, but usually the reaction is completed in 10 minutes to 100 hours. After completion of the reaction, the produced cyclohexene derivative can be isolated by various methods, but the following method is preferable because the rare earth catalyst can be easily recovered and reused.

The first method is a method in which the rare earth catalyst is separated from the reaction mixture as an aqueous solution, recovered and reused. That is, after adding a solvent amount of water to the reaction mixture,
The unreacted conjugated olefin, activated olefin, and cyclohexene derivative of the reaction product are separated from this aqueous solution by a solvent extraction method or the like to recover an aqueous solution containing a rare earth catalyst. Water is distilled off from this aqueous solution to isolate the rare earth catalyst.

The second method is a method of recovering a rare earth catalyst as a residue by separating unreacted conjugated olefin, active olefin, and cyclohexene derivative as a reaction product by a distillation method. In either method, the reaction product is isolated and purified by column chromatography, distillation, recrystallization, etc. according to a conventional method. On the other hand, the rare earth catalyst can be reused as the reaction catalyst of the present invention after further purification operation if necessary.

[0024]

According to the method of the present invention, it is considered that the rare earth catalyst functions as a so-called Lewis acid catalyst and becomes a good catalyst in the Diels-Alder reaction of the conjugated olefin and the active olefin. Further, this rare earth catalyst is well soluble in water, which facilitates separation from the reaction product, and the catalyst can be separated and reused easily.

[0025]

EXAMPLES The present invention will be specifically described below based on examples.

Example 1 10.0 g of methacrolein and 17.7 g of tris (trifluoromethanesulfonic acid) ytterbium were heated to 350 m.
It was dissolved in 1 methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours, 250 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, 5-norbornene-2-methyl-2-
It was found that the carboxaldehyde was produced in a yield of 77%. In addition, as a result of analysis with a nuclear magnetic resonance apparatus,
The ratio of the exo form and the endo form of 5-norbornene-2-methyl-2-carboxaldehyde was 93: 7.

Tris (trifluoromethanesulfonic acid) ytterbium 17.6 recovered by distilling water from the aqueous layer
g and 10.0 g of methacrolein were dissolved in 350 ml of methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours, 250 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, it was found that 5-norbornene-2-methyl-2-carboxaldehyde was produced in a yield of 75%. As a result of analysis by a nuclear magnetic resonance apparatus, the ratio of exo-form to endo-form of 5-norbornene-2-methyl-2-carboxaldehyde was 92: 8.

Example 2 35 g of 10.0 g of methyl vinyl ketone and 17.7 g of tris (trifluoromethanesulfonic acid) ytterbium were used.
It was dissolved in 0 ml of methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours, 250 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, it was found that 2-acetyl-5-norbornene was produced in a yield of 86%. Moreover, as a result of analysis by a nuclear magnetic resonance apparatus, 2-acetyl-5
-The ratio of exo-form to endo-form of norbornene is 10:90
Met.

Tris (trifluoromethanesulfonic acid) ytterbium 17.5 recovered by distilling water from the aqueous layer
g and 10.0 g of methyl vinyl ketone were dissolved in 350 ml of methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours, 250 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, it was found that 2-acetyl-5-norbornene was produced in a yield of 87%. Moreover, as a result of analysis by a nuclear magnetic resonance apparatus, 5-norbornene-2-methyl-
The ratio of the exo-form to the endo-form of 2-carboxaldehyde was 11:89.

Example 3 32.6 g of 1,4-naphthoquinone and 17.7 g of tris (trifluoromethanesulfonic acid) ytterbium were added.
It was dissolved in 50 ml of methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours, 250 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, it was found that 1,4,1a, 4a-tetrahydro-1,4-methanoanthracene-9,10-dione was produced in a yield of 93%. In addition, as a result of analysis with a nuclear magnetic resonance apparatus, in this reaction,
Only the endo body of 1,4,1a, 4a-tetrahydro-1,4-methanoanthracene-9,10-dione was selectively produced, and the endo body was not produced at all.

Tris (trifluoromethanesulfonic acid) ytterbium 17.6 recovered by distilling water from the aqueous layer
g and 10.0 g of 1,4-naphthoquinone were dissolved in 350 ml of methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours as it was, 50 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, 1,4,1a, 4a-tetrahydro-1,4
It was found that -methanoanthracene-9,10-dione was produced in a yield of 96%. As a result of analysis by a nuclear magnetic resonance apparatus, only the endo body of 1,4,1a, 4a-tetrahydro-1,4-methanoanthracene-9,10-dione was selectively produced, and the endo body was not produced at all. There wasn't.

Example 4 350 ml of 10.0 g of methacrolein and 14.0 g of scandium tris (trifluoromethanesulfonate)
Was dissolved in methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours as it was, 50 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, it was found that 5-norbornene-2-methyl-2-carboxaldehyde was produced in a yield of 96%. Moreover, as a result of analysis by a nuclear magnetic resonance apparatus,
The ratio of exo-form to endo-form of norbornene-2-methyl-2-carboxaldehyde was 11:89.

14.0 g of scandium (trifluoromethanesulfonate) scandium recovered by distilling water from the aqueous layer
And 10.0 g of methacrolein were dissolved in 350 ml of methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours, 250 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, it was found that 5-norbornene-2-methyl-2-carboxaldehyde was produced in a yield of 75%. As a result of analysis by a nuclear magnetic resonance apparatus, the ratio of exo-form to endo-form of 5-norbornene-2-methyl-2-carboxaldehyde was 92: 8.

Example 5 350 ml of 10.0 g of methacrolein and 14.0 g of scandium tris (trifluoromethanesulfonate)
Was dissolved in methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 2 hours as it was, 50 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, it was found that 5-norbornene-2-methyl-2-carboxaldehyde was produced in a yield of 96%. Moreover, as a result of analysis by a nuclear magnetic resonance apparatus,
The ratio of exo-form to endo-form of norbornene-2-methyl-2-carboxaldehyde was 11:89.

Examples 6 to 14 As in Example 4, various conjugated olefins (1) and various active olefins (2) were used, and 14.0 g of scandium tris (trifluoromethanesulfonate) was used as a catalyst. The reaction was carried out. The types and amounts of various conjugated olefins used at this time, the types and amounts of various active olefins, and the yield of the cyclohexene derivative (3) of the obtained reaction product were determined by analysis by a nuclear magnetic resonance apparatus. Table 1 shows the ratio of the exo-form to the endo-form of the cyclohexene derivative (3).

[0036]

[Table 1]

Example 15 350 ml of 10.0 g of methacrolein and 7.65 g of tris (trifluoromethanesulfonic acid) yttrium
Was dissolved in methylene chloride and cooled to 0 ° C. To this, 28.2 g of cyclopentadiene was added over 15 minutes, the mixture was stirred for 16 hours, 250 ml of water was added, and the mixture was extracted with methylene chloride. As a result of analyzing the organic layer by gas chromatography, 5-norbornene-2-methyl-2-
It was found that the carboxaldehyde was produced in a yield of 63%. In addition, as a result of analysis with a nuclear magnetic resonance apparatus,
The ratio of exo-form to endo-form of 5-norbornene-2-methyl-2-carboxaldehyde was 89:11.

Examples 16 to 27 28.2 g of cyclopentadiene was used as the conjugated olefin, and methacrolein 10.0 was used as the active olefin.
g, using various rare earth catalysts as catalysts,
The same reaction as in Example 15 was performed. The types and amounts of the various rare earth catalysts used at this time, the yield of the cyclohexene derivative (3) of the obtained reaction product, and the exo form of the cyclohexene derivative (3) determined by analysis by a nuclear magnetic resonance apparatus. Table 2 shows the ratio with the endo body.

[0039]

[Table 2]

[0040]

According to the method of the present invention, a rare earth catalyst is used when a conjugated olefin and an active olefin are reacted to produce a cyclohexene derivative, whereby the catalyst can be easily recovered after the reaction, In addition, the recovered catalyst can be reused if necessary, and
The reaction time can be shortened, and the cyclohexene derivative can be industrially advantageously produced.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location C07C 43/188 7419-4H 43/192 7419-4H 45/69 46/00 47/42 7188-4H 47/445 7188-4H 49/543 7188-4H 50/16 7188-4H 50/22 7188-4H 51/353 57/26 8930-4H 205/10 7188-4H 253/30 255/46 9357-4H C07D 263 / 22 // C07B 61/00 300 (72) Inventor Miharu Araki 1-20-60-203 Niikura, Wako-shi, Saitama (72) Inventor Waro Ishitani 1-9-5-203 Minamiikebukuro, Toshima-ku, Tokyo (72) Inventor Ken Takahori 940 New House, Aboshi Ward, Himeji City, Hyogo Prefecture

Claims (2)

[Claims] 1. The following general formula (1):(However, in the formula, R₁, R₂, R₃, R_Four, R_FiveAnd R₆
Is a hydrogen atom, alkyl group, alkenyl group, aryl group or
Represents an alkoxyl group, and R₁, R ₂, R
₃, R_Four, R_FiveAnd R₆Any two of them are integrated into a ring
May also form part of a structure)
And the following general formula (2):(However, in the formula, R₇, R₈, R₉And R_TenIs a hydrogen atom,
Halogen atom, alkyl group, alkenyl group, aryl
Group, alkoxyl group, acyloxy group, oxycarbonyl group
Group, amino group, nitro group, cyano group, sulfonyl group,
Haloformyl group, formyl group, carboxyl group, carba
A moyl group or an amidino group, and these R₇, R
₈, R₉And R_TenAny two of them are integrated into an annular structure
May form a part of. However, R₇, R₈, R₉as well as
R_TenAt least one of them is an alkenyl group or aryl
Group, alkoxyl group, acyloxy group, oxycarbonyl group
Group, amino group, halogen atom, nitro group, cyano group,
Sulfonyl group, haloformyl group, formyl group, carboxy
Silyl group, carbamoyl group or amidino group)
By reacting with an activated olefin represented by the following general formula (3):(However, in the formula, R₁, R₂, R₃, R_Four, R_Five, R₆,
R₇, R₈, R₉And R _TenIs the same as above)
In the method for producing a cyclohexene derivative,
As a medium, the following general formula (4) RE (OSO₂Rf)₃ (4) (where RE is a rare earth metal element and Rf is a
Rare-earth catalyst represented by a fluoroalkyl group)
Cyclohexene characterized by reacting in the presence of
Method for producing derivative. 2. The method for producing a cyclohexene derivative according to claim 1, wherein after the completion of the reaction, the rare earth catalyst used as the catalyst is recovered and the recovered catalyst is reused as the reaction catalyst.