JP2002088071A - Method for producing bicycloheptene derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing the cis-isomer of a bicycloheptene derivative easily, in high selectivity and in high yield from a compound of the general formula (1) comprising many isomers thereof. SOLUTION: This method for producing the cis-isomer of a bicycloheptene derivative of the general formula (3) is characterized by comprising the following process: the isomer mixture of a compound of the general formula (1) with the isomer molar ratio Z/E of (0:100) to (10:90) is irradiated with rays to form an isomer mixture with Z/E of (1:9) to (6:4), to which a cyclopentadiene derivative of the general formula (2) at 0.5-1.5 molar times the Z-isomer in the isomer mixture followed by heating. In the above formulas (1), (2) and (3), R1 is H or a 1-6C alkyl; Q is a (substituted) 5- or 6-membered heterocyclic group containing 1-4 N, O or S atom(s); R2 and R3 are each a 1-4C alkoxy or the like; and X is a halogen atom.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing a cis-isomer of a bicycloheptane derivative which is useful as an intermediate for producing agricultural chemicals and pharmaceuticals, particularly an intermediate for producing herbicidally active compounds, in a highly selective, high-yield, and simple manner. It relates to a method of manufacturing.

[0002]

2. Description of the Related Art General formula (3 ')

[0003]

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(Wherein R ¹ represents a hydrogen atom or a C1-C6 alkyl group, and R ² and R ³ each independently represent a C1-C6 alkyl group)
X represents a halogen atom;
Represents a 5- or 6-membered optionally substituted heterocyclic group containing 1 to 4 N, O or S atoms. Also, R ² and R ³ together may have a substituent C2~
A C3 alkylenedioxy group may be formed. (Hereinafter referred to as “bicycloheptene derivative”) is useful as an intermediate for producing pesticides and pharmaceuticals, particularly as an intermediate for producing herbicidally active compounds (for example, WO97 /
No. 41117, WO98 / 31681).

The bicycloheptene derivative is composed of a compound represented by the following general formula (1) and a compound represented by the following general formula (2) (hereinafter referred to as "cyclopentadiene derivative"): -Alder reaction (WO 00/03988)
Reference).

[0006]

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(Wherein, R ¹ , R ² , R ³ , X and Q have the same meanings as described above. In addition, a compound in which both R ¹ and Q are added to the end position is referred to as “cis isomer (Cis)”). , R ¹ is an isomer which Q is added to the end position in the exo position (Trans-
1) The isomer in which R ¹ is added to the endo position and Q is added to the exo position is referred to as (Trans-2). ) Among these stereoisomers, intermediates for the production of agricultural chemicals and medicaments, especially the above-mentioned WO 97/41117, WO 98 /
The cis isomer is useful as an intermediate for producing a herbicidally active compound disclosed in, for example, Japanese Patent No. 31681. Therefore, in the above reaction, it is necessary to efficiently produce the cis isomer.

[0008] In the Diels-Alder reaction between an ene such as a compound represented by the general formula (1) and a diene such as a compound represented by the general formula (2), an ene compound is generally used. It is known that a cis isomer of a 6-membered cyclic compound is mainly produced from the (Z) isomer, and a trans isomer is mainly produced from the (E) isomer. Therefore, if only the (Z) isomer of the compound represented by the general formula (1) is used, the cis isomer of bicycloheptene represented by the general formula (3) can be efficiently obtained.

However, the compound represented by the general formula (1) contains, as a main component, an isomer (E) which is easily synthesized and available, wherein Q is an ester group or an aldehyde group in the general formula (1). It is manufactured from the starting compound. Therefore, the compound represented by the general formula (1) can also be obtained as an isomer mixture containing a large amount of the (E) isomer, but it is complicated to separate the (Z) isomer from the isomer mixture and use it in the reaction. A simple separation step is required. Therefore, in a conventional method for producing a bicycloheptane derivative (WO00 / 03988 or the like), an isomer mixture of a compound represented by the general formula (1) is reacted with a cyclopentadiene derivative,
The bicycloheptene derivative is obtained as a mixture of isomers, and it has been difficult to produce the cis isomer of the bicycloheptene derivative useful as an intermediate for producing a herbicidally active compound in good yield.

[0010]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and uses (E) a compound represented by the general formula (1) containing a large number of isomers as a starting material,
An object of the present invention is to provide a method for industrially and advantageously producing a cis isomer of a bicycloheptane derivative in a highly selective, high yield, and simple manner.

[0011]

Means for Solving the Problems In order to solve the above problems, the present inventors have studied in detail the Diels-Alder reaction between a compound represented by the general formula (1) and a cyclopentadiene derivative. As a result, among the isomers of the compound represented by the general formula (1), it has been found that the (Z) isomer has higher reactivity with the cyclopentadiene derivative than the (E) isomer, and By using the present invention, the present invention has been completed.

That is, in the present invention, first, the isomer molar ratio is (Z) isomer: (E) isomer = 0: 100 to 10: 9
General formula (1) that is 0

[0013]

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Wherein R ¹ represents a hydrogen atom or a C1-C6 alkyl group, and Q represents one to four N, O or S atoms.
And represents a saturated or unsaturated 5- or 6-membered heterocyclic group which may have a substituent. ) Is photo-isomerized by irradiating a mixture of isomers of the compound represented by the formula (1) with an isomer molar ratio of (Z) isomer: (E) isomer = 1: 9 to 6:
4, a first step of obtaining an isomer mixture of the compound represented by the general formula (1), the isomer mixture obtained in the first step, and a compound represented by the general formula (1). Is 0.5 to 1.5 moles per mol of the (Z) isomer contained in the isomer mixture of the general formula (2)

[0015]

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(Wherein R ² and R ³ each independently represent C
X represents a 1 to C6 alkoxy group, and X represents a halogen atom. Further, R ² and R ³ are taken together to form a C 1 such as an ethylenedioxy or trimethylenedioxy group which may have a substituent.
A 2-C3 alkylenedioxy group may be formed. And a second step of heating the cyclopentadiene derivative represented by the formula (3) to a predetermined temperature.

[0017]

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(Wherein, R ¹ , R ² , R ³ , X and Q have the same meanings as described above). A process for producing a cis isomer of a bicycloheptene derivative represented by the formula:

The present invention secondly provides an isomer of the compound represented by formula (1) wherein the isomer molar ratio is (Z) isomer: (E) isomer = 0: 100 to 10:90. The mixture and the cyclopentadiene derivative represented by the general formula (2) in an amount of 0.1 to 1 mol per mol of the compound represented by the general formula (1) are irradiated with light at a predetermined temperature. And a method for producing a cis isomer of the bicycloheptene derivative represented by the general formula (3), characterized by heating. In the first and second inventions, it is preferable to perform light irradiation in the presence of a photosensitizer in order to increase the efficiency of the photoisomerization reaction.

According to the first aspect, the cis-isomer of the bicycloheptene derivative represented by the general formula (3) can be easily produced with high selectivity, high yield, and high yield.

According to the second aspect of the present invention, the desired cis isomer of the bicycloheptene derivative represented by the general formula (3) can be highly selectively obtained without going through two steps as in the first aspect. , High yield and simple production.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in detail. The present invention relates to a compound represented by the general formula (1), wherein the isomer molar ratio is (Z) isomer: (E) isomer = 0: 100 to
A 10:90 isomer mixture is used as starting material. First, the first step of irradiating the compound represented by the general formula (1) with light to perform photoisomerization will be described.

[0023]

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In the formula, R ¹ represents a hydrogen atom or a C1-C6 alkyl group such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl and t-butyl.

Q represents an optionally substituted saturated or unsaturated 5- or 6-membered heterocyclic group containing 1 to 4 N, O or S atoms.

(A) Specific examples of the 5-membered saturated heterocyclic group include 2-pyrrolidinyl, 3-pyrrolidinyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl, 3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 3
-Isothiazolidinyl, 4-isothiazolidinyl, 5-
Isothiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1,2,4-oxadiazolidine-3-
Yl, 1,2,4-oxadiazolidine-5-yl,
1,3,4-oxadiazolidine-2-yl, 1,2,2
4-thiadiazolidin-3-yl, 1,2,4-thiadiazolidin-5-yl, 1,3,4-thiadiazolidin-2-yl, 1,3,4-triazolidine-2-yl,
1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl, 1,3-dioxolan-2-yl, 1,
3-dioxolan-4-yl, 1,3-oxathiolan-2-yl group and the like,

(B) Specific examples of the 5-membered unsaturated heterocyclic group include 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2,3-dihydrofuran-2-yl, 2,3-
Dihydrofuran-3-yl, 2,3-dihydrofuran-
4-yl, 2,3-dihydrofuran-5-yl, 2,5
-Dihydrofuran-2-yl, 2,5-dihydrofuran-3-yl, 2,3-dihydrothiophen-2-yl,
2,3-dihydrothiophen-3-yl, 2,3-dihydrothiophen-4-yl, 2,3-dihydrothiophen-5-yl, 2,5-dihydrothiophen-2-yl, 2,5-dihydrothiophen -3-yl,

Pyrrole-2-yl, pyrrol-3-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, 2-imidazoline-2-
Yl, 2-imidazolin-4-yl, 2-imidazolin-5-yl, pyrazol-3-yl, pyrazol-4-
Yl, pyrazol-5-yl, oxazol-2-yl, oxazol-3-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-
Yl, isoxazol-4-yl, isoxazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,
3,4-oxadiazol-2-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,5-oxadiazole- 3-
Il,

2-thiazolyl, 4-thiazolyl, 5-thiazolyl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, 1,2,4-
Thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 1,2,3-thiadiazol-4-yl, 1,2,2
3-thiadiazol-5-yl, 1,2,5-thiadiazol-3-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,3,4
-Triazol-2-yl, 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, tetrazol-5-yl, 2-pyrrolin-1-yl, 2-
Pyrrolin-2-yl, 2-pyrrolin-3-yl, 2-pyrrolin-4-yl, 2-pyrrolin-5-yl, 2-oxazolin-2-yl, 2-oxazolin-4-yl, 2
-Oxazolin-5-yl, 3-oxazolin-2-yl, 3-oxazolin-4-yl, 3-oxazoline-
5-yl, 4-oxazolin-2-yl, 4-oxazolin-4-yl, 4-oxazolin-5-yl, 2-isoxazolin-3-yl, 2-isoxazolin-4
-Yl, 2-isoxazolin-5-yl, 3-isoxazolin-3-yl, 3-isoxazolin-4-yl, 3-isoxazolin-5-yl, 4-isoxazolin-3-yl, 4- Isoxazolin-4-yl,
4-isoxazolin-5-yl, 2-thiazoline-2
-Yl, 4-thiazolin-4-yl, 4-thiazoline-
5-yl, 2-isothiazolin-3-yl, 2-isothiazolin-4-yl, 2-isothiazolin-5-yl,
3-isothiazolin-3-yl, 3-isothiazoline-
4-yl, 3-isothiazolin-5-yl, 4-isothiazolin-3-yl, 4-isothiazolin-4-yl,
4-isothiazolin-5-yl, 1-pyrazolin-3-
Yl, 1-pyrazolin-4-yl, 1-pyrazolin-5
-Yl, 2-pyrazolin-3-yl, 2-pyrazolin-
4-yl, 2-pyrazolin-5-yl, 3-pyrazolin-3-yl, 3-pyrazolin-4-yl, 3-pyrazolin-5-yl group and the like,

(C) Specific examples of the 6-membered saturated heterocyclic group include 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 2-piperazinyl, morpholin-2-yl, morpholin-3-yl, 5,6- Dihydro-4H-1,3
-Thiazin-2-yl, 2-tetrahydropyranyl, 3
-Tetrahydropyranyl, 4-tetrahydropyranyl,
2-tetrahydrothiopyranyl, 3-tetrahydrothiopyranyl, 4-tetrahydrothiopyranyl group and the like,

(D) Specific examples of the 6-membered unsaturated heterocyclic group include 2-pyridyl, 3-pyridyl, 4-pyridyl,
-Pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyrazine-
2-yl 2H-pyran-3-yl, 2H-thiopyran-
And a 3-yl group.

Further, these groups may have one or more same or different substituents at any position of the hetero ring. Such substituents include, for example, C1-C4 alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl; chloromethyl, dichloromethyl, trichloromethyl, fluoro C1 to C4 haloalkyl groups such as methyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, and pentafluoroethyl; Among these, preferred specific examples of Q include the following Q-1 to Q-9

[0033]

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The groups represented by In the above formula, n
Is 0, 1 or 2, and R ′ is, for example, a C1-C4 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl group; C1-C4 haloalkyl groups such as dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl and the like; And so on.

The compound represented by the general formula (1) is an example
For example, methods described in the following documents (a) to (e)
It can be manufactured according to (A) Chim. Ind. (Milan). ,59
(1) 56 (1977): 3- (1-propenyl) -1
Production of H-pyrrole (b) Zh. Organ. Khim. ,2, 417 (1
996): 5- (1-propenyl) -isoxazole
Production of (c) J. Org. Chem. ,62, 3671 (19
97): 3- (1-propenyl) -2-isoxazolyl
(D) Heterocycles. ,22(11), 2
475 (1984): 4- (1-propenyl) pyridine
Production of (e) Heterocycles. ,29(1), 10
3 (1989): 5- (1-propenyl) -oxazo
Manufacturing

The photoisomerization of the compound represented by the general formula (1) can use ultraviolet light, visible light, or the like, and is preferably near ultraviolet light having a wavelength of 300 nm to 700 nm or visible light. As the light source, an incandescent bulb, a low-pressure mercury lamp, a high-pressure mercury lamp, or the like can be used. The irradiation time is usually 5 hours to 30 hours, preferably 10 hours to 2 hours.
0 hours. The temperature of photoisomerization is not particularly limited, but is usually room temperature to 100 ° C.

In the photoisomerization, it is considered that a photochemical equilibrium state exists. Therefore, all of the (E) isomers cannot be isomerized to the (Z) isomer. In general, the higher the intensity of the irradiation light, the sooner the photochemical equilibrium state is reached, and the longer the irradiation time, the closer to the photochemical equilibrium state. The irradiation light intensity and irradiation time can be appropriately selected, but in the present invention,
The isomer mixture in which (Z) isomer: (E) isomer = 1: 9 to 6: 4 can be directly used for the next reaction.

In this photoisomerization reaction, the reaction proceeds more smoothly when a photosensitizer such as aromatic ketones such as benzophenone, acetophenone and anthraquinone is added. The amount of the photosensitizer to be added is preferably from 0.001 mol to 0.1 mol per 1 mol of the compound represented by the general formula (1).

This photoisomerization reaction can be carried out without a solvent, but can also be carried out using a solvent. As a solvent used, a compound represented by the general formula (1) is dissolved,
There is no particular limitation as long as it is stable to light. Examples of the solvent used include aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene, chlorobenzene, and dichlorobenzene; ethanol, n-propyl alcohol, ethylene glycol, 1,3-butanediol, and ethylene glycol monomethyl ether. Alcohols; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N-dimethylimidazolidinone, N, N-dimethylimidazoline, hexamethylphosphoric triamide; Sulfur-containing hydrocarbons such as dimethyl sulfoxide and sulfolane; acetonitrile; These solvents can be used alone or as a mixed solution of two or more.

The abundance ratio (isomer molar ratio) of the isomer of the compound represented by the general formula (1) is determined by gas chromatography,
It can be measured by analysis means such as ¹ H-NMR. The isomer mixture of the compound represented by the general formula (1) is
It can be used for the next reaction as it is or after the solvent is distilled off under reduced pressure.

Next, the second step for producing the cis isomer (3) of the bicycloheptene derivative by reacting the obtained isomer mixture with the cyclopentadiene derivative (2) will be described.

[0042]

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In the cyclopentadiene derivative represented by the general formula (2), X represents a halogen atom. Examples of the halogen atom include fluorine, chlorine, and bromine atoms. Further, X may be all the same halogen atom or different halogen atoms.
R ² and R ³ each independently represent a C1 to C6 alkoxy group. As the C1-C6 alkoxy group, for example,
Methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy,
and a t-butoxy group. R ² and R ³ may be combined to form a C2 to C3 alkylenedioxy group such as an ethylenedioxy or trimethylenedioxy group. Further, the C2-C3 alkylenedioxy group is
It may have a substituent such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl and the like. Among them, compounds in which X is all chlorine atoms and R ² and R ³ are lower alkoxy groups such as methoxy group and ethoxy group are preferred.

This reaction is carried out, for example, in Tetrahedr.
on. , 42 , 1741 (1986); Org. C
hem. , 26 , 2066 (1961) and the like.

This reaction is carried out at room temperature to 250 ° C., preferably at 70 ° C. to 200 ° C., more preferably at 100 to 130 ° C. It is also possible to change the reaction temperature continuously. Further, for example, the reaction temperature may be maintained at 110 ° C. to 115 ° C. for several hours, then raised to 125 ° C. to 135 ° C., and maintained for several hours, and the reaction temperature may be divided into several stages. As a result, it is possible to suppress the generation of the trans-form which is a by-product.

The above reaction is carried out by adding a predetermined amount of a cyclopentadiene derivative to the reaction solution obtained in the first step and heating the reaction solution to a predetermined temperature. The amount of the cyclopentadiene derivative used is determined by the amount of the (Z) isomer 1 of the compound represented by the general formula (1) contained in the reaction solution obtained in the first step.
0.1 mol to 10 mol, preferably 0.5 mol
Mol to 1 mol.

This reaction is usually carried out without a solvent, but can be carried out using a solvent. As the solvent used, benzene, toluene, xylene, ethylbenzene,
Aromatic hydrocarbons such as chlorobenzene and dichlorobenzene; alcohols such as ethanol, n-propyl alcohol, ethylene glycol, 1,3-butanediol and ethylene glycol monomethyl ether; N, N-dimethylformamide, N, N-dimethyl Acetamide, N-
Amides such as methylpyrrolidone, N, N-dimethylimidazolidinone, N, N-dimethylimidazoline and hexamethylphosphoric triamide; sulfur-containing hydrocarbons such as dimethylsulfoxide and sulfolane; acetonitrile; They can be used alone or as a mixture of two or more.

The reaction is carried out by adding a polymerization inhibitor such as hydroquinone, diphenylpicrylhydrazyl and tri-p-nitrophenylmethyl, and a base such as sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate and potassium carbonate. It can be performed more smoothly. Polymerization inhibitor,
The amount of the base to be used is 0.0001 mol to 0.1 mol per 1 mol of the compound represented by the general formula (1).

In this reaction, among the (Z) and (E) isomers represented by the general formula (1), the (Z) isomer easily reacts with the cyclopentadiene derivative (the reaction rate is high,
Or high reactivity).
That is, the reaction solution obtained in the first step contains 10 mol%
The compound represented by the general formula (1) contains 60 mol% of the (Z) isomer and 40 mol% to 90 mol% of the (E) isomer. Add cyclopentadiene derivative as much as the abundance of
(Z) The isomer reacts preferentially with the cyclopentadiene derivative to give the cis isomer of the bicycloheptene derivative with high yield and high selectivity. In addition, since this reaction can be performed continuously, it is simple and convenient.
It is industrially advantageous.

The reaction solution contains, in addition to the target substance, the (E) isomer not used in the reaction, but the unreacted (E) isomer can be reused in the photoisomerization reaction.

As described above, the photoisomerization reaction and the Die
By continuously performing the ls-Alder reaction in two steps, the cis isomer of the bicycloheptene derivative can be produced with high selectivity, high yield, and simply.

In the present invention, the above reaction is carried out by one
It is also possible to carry out in a single step. That is, the isomer molar ratio is (Z) isomer: (E) isomer = 0: 100-1.
By heating an isomer mixture of the compound represented by the general formula (1) at a ratio of 0:90 and a predetermined amount of a cyclopentadiene derivative represented by the general formula (2) to a predetermined temperature under light irradiation, The cis isomer of the bicycloheptene derivative can also be produced.

The amount of the cyclopentadiene derivative to be used is 0.1 mol to 10 mol, preferably 0.1 mol to 1 mol, per 1 mol of the compound represented by the general formula (1).
More preferably, the abundances of the (Z) isomer and the (E) isomer in the photochemical isomerization state of the compound represented by the general formula (1) are determined in advance, and based on the abundances, ) Add as much cyclopentadiene derivative as the amount of isomer and heat.

This reaction is carried out at room temperature to 250 ° C., preferably at 70 ° C. to 200 ° C., more preferably at 100 to 130 ° C. It is also possible to change the reaction temperature during the reaction. Alternatively, the reaction temperature may be maintained at 110 ° C. to 115 ° C. first, then raised to 125 ° C. to 135 ° C., and held for several hours, and the reaction temperature may be changed in several steps. As a result, it is possible to suppress the generation of the trans-form which is a by-product.

The conditions for light irradiation and the reaction solvent in this reaction can be carried out in the same manner as in the first invention.
As in the case of the first reaction, it is preferable to add a photosensitizer such as an aromatic ketone such as benzophenone, acetophenone and anthraquinone since the reaction proceeds more smoothly.

The reaction can be carried out without a solvent, but can also be carried out using a solvent. As the solvent used,
Aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene, chlorobenzene, and dichlorobenzene; alcohols such as ethanol, n-propyl alcohol, ethylene glycol, 1,3-butanediol, and ethylene glycol monomethyl ether; N, N -Dimethylformamide, N, N-dimethylacetamide, N-
Amides such as methylpyrrolidone, N, N-dimethylimidazolidinone, N, N-dimethylimidazoline and hexamethylphosphoric triamide; sulfur-containing hydrocarbons such as dimethylsulfoxide and sulfolane; acetonitrile; Or a mixture of two or more

The addition of a polymerization inhibitor such as hydroquinone, diphenylpicrylhydrazyl, tri-p-nitrophenylmethyl, or a base such as sodium hydrogencarbonate, potassium hydrogencarbonate, sodium carbonate, potassium carbonate, or the like, is also effective in the reaction. This is preferable in order to perform the operation more smoothly.

By the above-mentioned method, the cis isomer of the bicycloheptene derivative can be produced in a single step with high selectivity, high yield, and simple.

In this reaction, the compound represented by the general formula (1) containing a large amount of the (E) isomer is photoisomerized, and the (Z) isomer formed by photoisomerization is present in the system. It selectively reacts with the cyclopentadiene derivative to obtain the desired cis isomer of the bicycloheptene derivative.

[0060]

Next, the present invention will be described in more detail by way of examples. The present invention is not limited to the following Examples, and can freely select the compounds represented by the general formulas (1) to (3), the type of the solvent, the type of the base to be used, and the like without departing from the gist of the present invention. Can be changed.

Example 1 Cis-1,2,3,4-tetrachloro-6-methyl-
Production of 7,7-dimethoxy-5- (2-oxazolin-3-yl) -bicyclo [2.2.1] hepta-2-ene

[0062]

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(E) -3-E contains 3 mol% of isomer
111 g of (1-propenyl) -2-isoxazoline was dissolved in 890 ml of toluene, and 9 g of benzophenone was added as a photosensitizer. The solution was irradiated with light from a high-pressure mercury lamp (400 W) for 10 hours under a nitrogen stream. From the reaction solution, toluene was distilled off under reduced pressure to obtain 111 g of an isomer mixture consisting of (Z) isomer: (E) isomer = 30: 70 (molar ratio). In addition, the abundance of isomers
It was determined by measuring by gas chromatography.

Then, 111 g of the isomer mixture obtained above was obtained.
51.8 g (0.2 mol) of 1,1-dimethoxy-2,3,4,5-tetrachlorocyclopentadiene was added to the mixture, and the mixture was heated at 110 to 115 ° C. for 5 hours at 125 to 130 ° C.
For 8 hours. When the obtained reaction product was analyzed by high performance liquid chromatography, Cis-1,
2,3,4-tetrachloro-6-methyl-7,7-dimethoxy-5- (2-isoxazolin-3-yl) -bicyclo [2.2.1] hept-2-ene was obtained in a yield of 95. %
(Based on cyclopentadiene).

[0065]

As described above, according to the present invention,
A cis-isomer of a bicycloheptane derivative useful as an intermediate for producing pesticides and pharmaceuticals, particularly an intermediate for producing a herbicidally active compound, can be produced with high yield, high selectivity, and simply.

Claims (3)

[Claims] 1. The general formula (1) wherein the molar ratio of the isomers is (Z) isomer: (E) isomer = 0: 100 to 10:90. (In the formula, R ¹ represents a hydrogen atom or a C1-C6 alkyl group, and Q represents a 5- or 6-membered heterocyclic group which may have a substituent and has 1-4 N, O or S atoms. ), The isomer mixture of the compound represented by the formula (I) is irradiated with light to give an isomer molar ratio of (Z) isomer: (E) isomer = 1:
A first step of obtaining an isomer mixture of the compound represented by the general formula (1), which is 9 to 6: 4; an isomer mixture obtained in the first step; The compound represented by the general formula (2) is 0.5 to 1.5 times the mol of the (Z) isomer contained in the isomer mixture of the compound represented by the formula (2). (Wherein represents R ² and R ³ are independently a C1~C6 alkoxy group, X represents a halogen atom. In addition, R ²
And R ³ together form C2 which may have a substituent
~ C3 alkylenedioxy groups may be formed. And a second step of heating the cyclopentadiene derivative represented by the general formula (3) to a predetermined temperature. (In the formula, R ¹ , R ² , R ³ , X and Q have the same meanings as described above.) A method for producing a cis isomer of a bicycloheptene derivative represented by the formula: 2. An isomer mixture of the compound represented by the general formula (1) wherein the molar ratio of the isomers is (Z) isomer: (E) isomer = 0: 100 to 10:90; Heating the cyclopentadiene derivative represented by the general formula (2) to a predetermined temperature while irradiating the compound with the compound represented by the general formula (2) in an amount of 0.1 to 1 mol per mol of the compound represented by the formula (1). A method for producing a cis isomer of a bicycloheptene derivative represented by the general formula (3). 3. The method according to claim 1, wherein the light irradiation is performed in the presence of a photosensitizer.
Or a method for producing a cis isomer of a bicycloheptene derivative represented by the general formula (3).