JPH09221444A - Stereoselective production of cis-substituted bicycloheptanedione derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To stereoselectively, economically advantageously produce only a cis isomer of a bicycloheptane-2,4-dione derivative useful as an intermediate raw material of a herbicide. SOLUTION: This derivative of formula I (R<1> and R<2> are each a 1-6C alkyl) is obtained by reacting an α-alkoxy-α-alkyl acetate of formula II (R<3> is a 1-6C alkyl) with lithium amides of formula III (R<4> and R<5> are each a 1-6C alkyl or trimethylsilyl) and reacting with a trialkylsilyl halide of the formula XSiR<a> R<b> R<c> (R<a> -R<c> are each a 1-4C alkyl; X is halogen) to obtain ketene silyl acetal of the formula R<1> (R<2> O)C=C(OR<3> )OSiR<a> R<b> R<c> , then reacting with 1- halogeno-2-pentene-4-one of formula IV (Y is a halogen) in the presence of a Lewis acid (e.g. aluminum chloride), and further reacting with a base (e.g. sodium methoxide). The compound of the formula I can be introduced to 3- substituted benzoyl-bicycloheptane-2,4-dione derivative useful as a herbicide.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a compound of formula (VI) useful as a herbicide.

[0002]

Embedded image

A compound of formula (I) which is an intermediate for the production of a 3-benzoyl-bicycloheptane-2,4-dione derivative represented by

[0004]

Embedded image

The present invention relates to a technique for stereoselectively producing a cis isomer of a bicycloheptane-2,4-dione derivative represented by

[0006]

2. Description of the Related Art WO91 / disclosed by the present applicants
The 3-benzoylbicycloheptane-2,4-dione derivative described in No. 00260 is a compound having excellent herbicidal activity. And in the specification, there are cis and trans isomers between the substituent at the 5-position of the bicycloheptanedione ring and the bicyclo ring, and the herbicidal activity and crop selectivity differ depending on the type of isomer. It is disclosed that there may be. In addition, the present inventors
No. 2/00084 discloses a stereoselective method for producing a bicycloheptane-2,4-dione derivative in which the 5-position of the bicycloheptanedione ring is substituted with an alkyl group or an alkoxycarbonyl group. In addition, we have:
In the previous application (International Application JP 95/02259), it is disclosed that a compound in which a methyl group and an alkoxy group are substituted at the 5-position of the bicycloheptanedione ring gives particularly excellent herbicidal activity and compound stability. However, a method for stereoselectively producing a compound in which an alkyl group and an alkoxy group are substituted at the 5-position of the bicycloheptanedione ring has not yet been known.

[0007]

An object of the present invention is to provide a technique for stereoselectively producing only the cis isomer of the above bicycloheptane-2,4-dione derivative.

[0008]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that α-
Alkoxy-α-alkyl acetic acid ester was used to form a silyl enol ether by reacting lithium amides with γ-halogeno-ether in the presence of Lewis acid.
It was found that the desired cis isomer (I) of the bicycloheptane-2,4-dione derivative can be efficiently produced by adding an α, β-unsaturated ketone and then performing a ring closure reaction with a base. The present invention has been completed. Hereinafter, the present invention will be described in detail.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention includes the following (1) and (2).
And a step (3), which is a stereoselective method for producing a bicycloheptane-2,4-dione derivative represented by the formula (I).

[0010]

Embedded image

(In the formula, R ¹ and R ² each independently represent a linear or branched C _1-6 alkyl group such as a methyl, ethyl, propyl, isopropyl, butyl or t-butyl group. )

(1) Formula (II)

[0013]

Embedded image

(In the formula, R ¹ and R ² have the same meanings as described above, and R ³ is a linear or branched C such as methyl, ethyl, propyl, isopropyl, butyl or t-butyl group.
Represents a _1-6 alkyl group. ) Α-alkoxy-
The α-alkyl acetic acid ester has the formula (III)

[0015]

Embedded image

(Wherein R ⁴ and R ⁵ are each independently a linear or branched C _1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl group or a trimethylsilyl group. Represented by the general formula XSiR ^a R ^b R ^c (R ^a , R ^b , and R ^c are methyl, respectively), such as trimethylsilyl chloride and t-butyl-dimethylsilyl chloride. (A linear or branched C _1-4 alkyl such as ethyl, propyl, isopropyl, butyl or t-butyl group is represented, and X represents a halogen atom such as chlorine atom.)
In addition to the trialkylsilyl halide represented by the general formula (IV)

[0017]

Embedded image

(Wherein R ¹ , R ² , R ³ , R ^a , R ^b ,
R ^c has the same meaning as described above. ) In the step of isolating the ketene silyl acetal, and (2) in the reaction product of the step (1) in the presence of a Lewis acid, the compound of formula (V)

[0019]

Embedded image

(In the formula, Y represents a halogen atom such as chlorine and bromine.) 1-halogeno-2-pentene-
Reacting 4-one. (3) By reacting the reaction product of the step (2) with a base, the compound of the general formula (I)

[0021]

Embedded image

The cis isomer of the bicycloheptane-2,4-dione derivative represented by the formula (3) is stereoselectively produced.

As the α-alkoxy-α-alkyl acetic acid ester which can be used in the step (1), methyl α-methoxypropionate, ethyl α-methoxypropionate, methyl α-ethoxypropionate, α- Ethyl ethoxypropionate, methyl α-propoxypropionate, ethyl α-propoxypropionate, methyl α-isopropoxypropionate, ethyl α-isopropoxypropionate, methyl α-butoxypropionate, ethyl α-butoxypropionate, etc. It can be illustrated. Usually, the ester used is selected so that the ester residue of the ester matches the alkoxy part of the alkoxide used in step (3).

Examples of the lithium amides that can be used in the above step (1) include compounds represented by the general formula (III). Lithium amides are generally produced from alkyllithium and amines, but when they are prepared immediately before use in the reaction, those already prepared may be used. Examples of more preferable lithium amides include lithium diisopropylamide (for example, obtained from n-butyllithium and diisopropylamine) and lithium bis (trimethylsilyl) amide.

In this step, the amount of lithium amides used is usually preferably 1.0 to 2.0 mol per 1.0 mol of α-alkoxy-α-alkyl acetic acid ester.

In the above step (1), examples of the reaction solvent that can be used include ethers such as tetrahydrofuran and diethyl ether, and hydrocarbons such as toluene and xylene. The reaction is -78
It progresses smoothly in the range of ℃ to room temperature.

In the above step (2), Lewis acids that can be used include titanium tetrachloride, ferric chloride,
Examples include stannic chloride, aluminum chloride, zinc chloride and the like.

Also, in this step, the Lewis acid used and 1-halogeno-2-pentene-4 to be reacted are used.
The amount of -one (V) used is usually α-alkoxy-α-
For each 1.0 mol of alkyl acetate ester, 0.
1-3.0 mol and 0.5 mol-2.0 mol are preferable.

In the above step (2), examples of the reaction solvent that can be used include ethers such as tetrahydrofuran and diethyl ether, and hydrocarbons such as toluene and xylene. The reaction is -78
It can be carried out in the temperature range of 0 ° C to the boiling point of the solvent used.

In the above step (3), as a base which can be used, an alkali such as sodium methylate, sodium ethylate, potassium methylate, potassium ethylate, potassium t-butyrate, magnesium methylate or magnesium ethylate can be used. Examples include metal alkoxides and alkaline earth metal alkoxides.

In the step (3), reaction solvents that can be used include, for example, alcohols such as methanol and ethanol, ethers such as diethyl ether and tetrahydrofuran, hydrocarbons such as benzene and toluene, and DMF. The amides of

In this step, the amount of the base used is usually 2.0 to 4.0 mol, based on 1.0 mol of the product of the step (2), and the reaction is -78. It can be carried out in the temperature range of 0 ° C to the boiling point of the solvent used.

After the completion of the reaction in each of the above steps, the target product can be obtained by separating and purifying by a post-treatment operation by a usual synthetic chemical method. In addition, the identification of the reaction product
The measurement was carried out by NMR, MASS and IR spectra. The chemical structural formula of the bicycloheptanedione derivative shown in this specification is 5
The relative configuration with respect to the position substituent is shown for convenience, not the absolute configuration. Further, the raw material compound, the production intermediate and the compound of the present invention may have an optically active compound, a stereoisomer and a tautomer. All such compounds are included within the scope of this invention.

[0034]

Next, the present invention will be described in more detail with reference to examples. (Example 1) Production of methoxyketene methyltrimethylsilyl acetal

[0035]

Embedded image

To 300 ml of anhydrous diethyl ether was added 42 ml (0.54 mol) of diisopropylamine,
After cooling to 70 ° C., 325 ml (0.52 mol) of n-butyllithium 1.6M hexane solution was added and stirred for 30 minutes to prepare lithium diisopropylamide. In the obtained lithium diisopropylamide solution (LDA), 59 g of methyl 2-methoxypropionate (0.5 m
ol) was slowly added dropwise and stirred for 30 minutes. Furthermore, trimethylsilyl chloride (TMSCl) 82.5
ml (0.89 mol) was slowly added dropwise, and after completion of the addition, the mixture was further stirred at 0 ° C. for 1 hour. Water and then saturated aqueous sodium hydrogen carbonate solution were added to the reaction solution to terminate the reaction, and the mixture was extracted with diethyl ether. The organic layer was dried over magnesium sulfate and the solvent was distilled off under reduced pressure to obtain 90 g of an oily substance as a target substance (yield 95%).

¹ H-NMR data (CDCl ₃ , δpp
m): 3.48 (s, 3H, OCH ₃ ), 3.43
(S, 3H, OCH ₃ ), 1.76 (s, 3H, C
_{H 3), 0.23 (s,} 9H, Si (CH 3) 3)

(2) 5-ethoxy-5-methylbicyclo
Production of [4,1,0] heptane-2,4-dione (cis)

[0039]

Embedded image

To 500 ml of methylene chloride, 66.2 g (0.5 mol) of anhydrous aluminum chloride was added, and 53.5 g (0.45 mo) of 1-chloro-2-penten-4-one was added.
1) was added and the mixture was heated under reflux for 10 minutes. 90 g (0.47 mol) of methoxyketenemethyltrimethylsilyl acetal obtained in (1) was added dropwise thereto, and the mixture was refluxed for 1 hour, ice water was added to the reaction solution, and the mixture was extracted with methylene chloride. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To the obtained crude addition product, 95 g (0.49 mol) of sodium methoxide 28% methanol solution and 300 ml of methanol were added, and the mixture was stirred at room temperature for 3 hours.
Water and diluted hydrochloric acid were added to the reaction solution to make it acidic, and the mixture was extracted with methylene chloride. The extract was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude cyclized crude product. 173.5 g (0.9 mol) of a 28% methanol solution of sodium methoxide was added to the obtained crude cyclized product, and the mixture was refluxed for 24 hours. Water and diluted hydrochloric acid were added to the reaction solution to adjust the pH to 11, and the mixture was extracted with methylene chloride. Dilute hydrochloric acid was added to the aqueous layer to adjust the pH to 3, and the mixture was extracted with methylene chloride. The obtained organic layers were combined, washed with water and saturated brine, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 28 g (yield 38%) of a white powder. Melting point 10
8-109 ° C ( ¹ H-NMR: δppm) 3.45 (s, 3H, O
_{CH 3), 3.19 (m,} 2H, CH 2), 2.22
(M, 1H), 1.47 ( s, 3H, CH 3), 1.2
3 (m, 1H)

Reference Example 1 5-Methoxy-3- (4-methylsulfonyl-2-nitrobenzoyl) -5-methylbicyclo [4.1.0] heptane-2,4-dione (cis
)Manufacturing of

[0041]

Embedded image

5-methoxy-5-methylbicyclo [4.1.
0] 2.1 g of heptane-2,4-dione (cis) (1
2.5 mmol) was dissolved in 20 ml of methylene chloride, 1.4 g (13.9 mmol) of triethylamine was added, and the mixture was stirred at room temperature for 10 minutes. 3-methoxy-2-
Methyl-4-methylsulfonylbenzoyl chloride
3.28 g (12.5 mmol) was added, and the mixture was further stirred for 2 hours. Water and diluted hydrochloric acid were added to the reaction solution and extracted with methylene chloride, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product of O-benzoyl compound. This product was purified by silica gel column chromatography (eluting with a mixed solvent of benzene: ethyl acetate = 4: 1),
2.34 g of a viscous liquid was obtained (48% yield). 2.34 g (5.94 mmol) of the obtained O-benzoyl compound was dissolved in 20 ml of acetonitrile, 0.7 g (6.9 mmol) of triethylamine and 0.1 g (1.2 mmol) of acetone cyanohydrin were added, and the mixture was stirred at room temperature. Stir for 5 hours. Water and diluted hydrochloric acid were added to the reaction solution to make it acidic, and the mixture was extracted with methylene chloride. Purification by silica gel chromatography (eluting with a mixed solvent of chloroform: methanol = 50: 1) gave the title compound as white crystals (1.02 g).
(Yield 44%) was obtained. Melting point 165-168 ° C This compound has excellent herbicidal activity and is useful as a herbicide.

[0043]

INDUSTRIAL APPLICABILITY As described above, the present invention provides 3-substituted benzoyl-bicycloheptane-useful herbicides.
This is a method for stereoselectively producing only the cis isomer of the bicycloheptane-2,4-dione derivative, which is an intermediate raw material of the 2,4-dione derivative. The method of the present invention uses only industrially inexpensive raw materials and is extremely economical.

Claims (4)

[Claims] 1. A process for producing a cis isomer of a bicycloheptane-2,4-dione derivative represented by the formula (I), which comprises the following steps (1), (2) and (3): Law. Embedded image (In the formula, R ¹ and R ² each independently represent a linear or branched C _1-6 alkyl group.) (1) Formula (II) (In the formula, R ¹ and R ² represent the same meaning as described above, and R ³ represents a linear or branched C _1-6 alkyl group.) Α-alkoxy-α-alkyl acetic acid ester And has the formula (III) (In the formula, R ⁴ and R ⁵ each independently represent a linear or branched C _1-6 alkyl group or a trimethylsilyl group.) And reacted with a lithium amide represented by the general formula XSiR ^a R A trialkylsilyl halide represented by ^b R ^c (R ^a , R ^b , and R ^c each represent a linear or branched C _1-4 alkyl, and X represents a halogen atom), and a compound represented by the general formula (IV) (In the formula, R ¹ , R ² , R ³ , R ^a , R ^b and R ^c have the same meanings as described above.) A step of isolating the ketene silyl acetal. (2) In the reaction product of the step (1), in the presence of a Lewis acid, the compound of the formula (V): (In the formula, Y represents a halogen atom.) A step of reacting 1-halogeno-2-penten-4-one. (3) A step of reacting the reaction product of the step (2) with a base to obtain a cis isomer of the bicycloheptane-2,4-dione derivative represented by the general formula (I): 2. The bicycloheptane-2,4- according to claim 1, wherein the lithium amide used in the step (1) is lithium diisopropylamide or lithium bis (trimethylsilyl) amide.
Process for producing cis isomer of dione derivative. 3. The Lewis acid used in step (2) is one selected from the group consisting of titanium tetrachloride, ferric chloride, stannic chloride, aluminum chloride and zinc chloride. The method for producing the cis isomer of the bicycloheptane-2,4-dione derivative according to claim 1. 4. The cis isomerization of the bicycloheptane-2,4-dione derivative according to claim 1, wherein the base used in the step (3) is an alkali metal alkoxide or an alkaline earth metal alkoxide. Body manufacturing method.