JP2000191554A - Production of acrylic acid derivative having functional group having high reaction activity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrial method for producing the subject acrylic acid derivative which is economically excellent, capable of selectively and highly efficiently obtaining in high yield by reacting a specific ketoester derivative with a specific alcohol in the presence of an acid catalyst. SOLUTION: A ketoester derivative of formula I (X is a group eliminating when reacted with a nucleophilic reagent; Y and Z is each H, a halogen, an alkyl, a cycloalkyl or the like; R1 is an alkyl, a cycloalkyl, an alkenyl or the like; and R2 is H, an alkyl, a cycloalkyl or the like) or formula II is reacted with an alcohol of the formula R11OH (R11 is an alkyl, a cycloalkyl, an alkenyl or the like) in the presence of an acid catalyst to provide the objective compound of formula III. The compound of formula I which becomes a raw material can be synthesized by reacting a phenylacetic acid derivative with esters or orthoester in the presence of a Lewis acid or a base.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to compounds useful as intermediates for agricultural chemicals and pharmaceuticals, and more particularly to acrylic acid derivatives useful as intermediates for agricultural chemicals and pharmaceuticals, especially functional groups having high reactivity in the molecule. For example, the present invention relates to a method for producing an acrylic acid derivative having a functional group such as a monohalogenated methyl group with high yield and efficiency with high selectivity.

[0002]

2. Description of the Related Art Acrylic acid derivatives are important as raw materials and intermediates of agricultural chemicals and pharmaceuticals, and particularly, the following compounds are known as fungicides and insecticides.

Embedded image It is required to efficiently synthesize the compound represented by the general formula (III) as a synthetic intermediate of these compounds. Conventionally, as a method for synthesizing the compound represented by the general formula (III), for example, as shown in the following formula, WO94 is a method in which a benzyl methyl group is brominated under light irradiation using a deoxidizing agent polymer as a catalyst and bromine. / 05620.

Embedded image However, there are problems such as the necessity of equipment for light irradiation, the difficulty of controlling the reaction due to the radical reaction, the low yield of about 60%, and the use of a large amount of bromine. EP 0 299 694 discloses that instead of bromine N
Although an example using BS is described, the yield was not satisfactory. In any case, since a halogen atom is introduced in the final step, other functional groups are attacked by the halogenating agent and cause a decrease in yield, and furthermore, purification from by-products is difficult. Was.

[0003] Further, although there is no specific description in EP178826, it is described that the compound represented by the general formula (III) can be synthesized under relatively mild conditions as shown in the following formula.

Embedded image However, when a similar reaction is carried out using a starting material having an active halogen atom which is easy and inexpensive, for example, methyl 2-chloromethylphenylacetate, the dimerization reaction of the starting material or intramolecular The cyclization reaction was prioritized and the yield of the desired product was low. Further, since an expensive reaction reagent is used, it is industrially disadvantageous.

[0004]

The introduction of highly reactive functional groups in the final step is advantageous because it is not affected by side reactions due to those functional groups in an intermediate step. However, satisfactory results were not obtained in terms of yield and isolation and purification. Conversely, when starting from a phenylacetic acid derivative having a highly reactive functional group in the molecule and leading to an acrylic acid derivative while leaving the highly reactive functional group in the molecule, unnecessary by-products are produced. Satisfactory results have not been obtained, such as a decrease in yield or the need to use expensive reagents. The present invention provides an economical method capable of selectively obtaining a high-yield, high-efficiency acrylic acid derivative represented by the general formula (III) by a novel method without affecting a highly reactive functional group in a molecule. It is intended to provide an industrially superior production method.

[0005]

The present invention has been made as a result of intensive studies to solve the above-mentioned problems. As a result, a phenylacetic acid derivative corresponding to an acrylic acid derivative having a highly reactive functional group in the molecule and an ester or orthoester A novel ketoester derivative (I) is produced by the action of a Lewis acid and a base on a compound, and a novel ketoester derivative (I) is produced. Then, the acetalization is carried out with an alcohol under neutral to acidic conditions to obtain a novel acetal derivative (V). Thus, the present invention was completed by continuing the reaction under neutral to acidic conditions, and finding a method for producing the desired acrylic acid derivative with high selectivity and high yield by dealcoholation.

That is, the present invention provides a compound represented by the general formula (I)

Embedded image (Wherein, X represents a group which is eliminated when reacted with a nucleophile, and Y and Z may be the same or different and each represent a hydrogen atom, a halogen atom, an alkyl group, a cycloalkyl group,
Alkenyl group, alkynyl group, haloalkyl group, alkoxyalkyl group, aryl group, heteroaryl group, aralkyl group, alkoxy group, haloalkoxy group, allyloxy group, propargyloxy group, arylalkoxy group, aryloxy group, heteroaryloxy group, acyloxy group, an amino group, an arylazo group, an acylamino group, a nitro group, a cyano group, -CO ₂ R _3, -CONR _{4
R 5, -COR 6, -CR 7} = NR 8, or -N = CR
₉ represents R _10, and when Y and Z are adjacent to each other, forms an aliphatic or aromatic fused ring or a heterocyclic ring containing at least one hetero atom, and R ₁ represents an alkyl group, a cycloalkyl group,
Represents an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group, wherein R _{2 to} R ₇ , R ₉ and R ₁₀ may be the same or different, and may be a hydrogen atom, an alkyl group; Represents a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group, and R ₈ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group. Represents a group, a heteroaryl group, an aralkyl group, a cycloalkylalkyl group, or an alkoxy group. The ketoester derivative represented by the general formula (II)

Embedded image (In the formula, R ₁₁ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, an aralkyl group, or a cycloalkylalkyl group.)
With an alcohol represented by the general formula (III)

Embedded image (Wherein, X, Y, Z, R ₁ , R ₂ , and R ₁₁ represent the same groups as described above).

The general formula (I)

Embedded image (Wherein, X, Y, Z, R ₁ and R ₂ represent the same groups as described above).
I)

Embedded image (Wherein, R ₁₁ represents the same group as described above), and general formula (IV)

Embedded image (In the formula, R ₁₂ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, an aralkyl group, or a cycloalkylalkyl group.)
With an orthoester represented by the formula (III):

Embedded image (Wherein, X, Y, Z, R ₁ , R ₂ , and R ₁₁ represent the same as described above).

Further, the general formula (I)

Embedded image (X, Y, Z, R ₁ , and R ₂ represent the same groups as described above), and a general formula (V)

Embedded image (Wherein, X, Y, Z, R ₁ , R ₂ , and R ₁₁ represent the same as described above).

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION In the general formula (I), X is not particularly limited as long as it is a group which can be eliminated by the attack of a nucleophile and undergoes a nucleophilic substitution reaction. A halogen atom, a substituted or unsubstituted arylsulfonyloxy group, a lower alkylsulfonyloxy group, a trifluoromethanesulfonyloxy group, or a trialkylammonium group, more preferably a chlorine atom, a bromine atom, an iodine atom, p- Examples thereof include a toluenesulfonyloxy group and a methanesulfonyloxy group, and a chlorine atom is particularly preferable.

In the formula (I), Y and Z may be the same or different, and represent a hydrogen atom, a halogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, a haloalkyl group, an alkoxyalkyl group. , Aryl group, heteroaryl group, aralkyl group, alkoxy group,
Haloalkoxy, allyloxy, propargyloxy, arylalkoxy, aryloxy, heteroaryloxy, acyloxy, amino, arylazo, acylamino, nitro, cyano,-
_{CO 2 R 3, -CONR 4 R} 5, -COR 6, -CR 7 = NR
₈ , or -N = CR ₉ R ₁₀ , when Y and Z are adjacent to each other, form an aliphatic or aromatic condensed ring or a heterocyclic ring containing at least one hetero atom, and R _{3 to} R ₇ , R ₉ and R ₁₀
May be the same or different, a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group,
Represents an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group, wherein R ₈ is a hydrogen atom,
Represents an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, a cycloalkylalkyl group, or an alkoxy group. Specifically, hydrogen atom, chlorine atom, bromine atom,
Iodine atom, fluorine atom, methyl group, vinyl group, allyl group, ethynyl group, propargyl group, chloromethyl group, benzyl group, phenyl group, pyridyl group, methoxy group, phenoxy group, pyridyloxy group, allyloxy group, propargyloxy group , P-chlorobenzyloxy group, acetoxy group, dimethylamino group, phenylazo group, acetamido group, nitro group, cyano group, methoxycarbonyl group,
Examples thereof include a dimethylcarbamoyl group, an acetyl group, an N-phenylimino group, an N-hydroxyimino group, a benzylideneamino group, a condensed pyridine ring, and a condensed imidazole ring.

In the general formula (I), R ₁ represents an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group or a cycloalkylalkyl group. Specific examples include a methyl group, an ethyl group, an allyl group, a propargyl group, a benzyl group, a cyclohexyl group, a phenyl group, and a 2-pyridyl group. R ₂ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group. Specifically, a hydrogen atom,
Examples thereof include a methyl group, an ethyl group, an allyl group, a propargyl group, a benzyl group, a cyclohexyl group, a phenyl group, and a 2-pyridyl group.

The ketoester used in the present invention is not particularly limited as long as it is a compound represented by the general formula (I). Specific examples are shown in Table 1 (Tables 1001 to 100).
3]).

[0013]

[Table 1001]

[0014]

[Table 1002]

[0015]

[Table 1003]

The ketoester derivative represented by the general formula (I) is described, for example, in M.S. N. It can be synthesized by reacting with esters and orthoesters in the presence of a Lewis acid and a base by applying the conditions of Deshumuk et al. (Synth. Commun., 1996, 26, 1657). Specifically, the following formula can be exemplified using 2-chloromethylphenylacetic ester as a starting material.

Embedded image The Lewis acid used in this reaction is not particularly limited, and a general one can be used.
Tin chloride, iron chloride, titanium chloride, alkoxytitanium chloride, alkoxytitanium, boron trifluoride diethyl ether complex and the like can be preferably used, and titanium tetrachloride and aluminum chloride are particularly preferable. As the base used in this reaction, a general base can be used, but tertiary alkylamines such as diisopropylethylamine and triethylamine are preferable.

Further, as the solvent used for synthesizing the compound represented by the general formula (I), general solvents which can be used industrially can be used, and hydrocarbons such as hexane, cyclohexane and Isopar E can be used. And halogenated hydrocarbons such as methylene chloride and chloroform, and aromatic hydrocarbons such as toluene and chlorobenzene. The amount of the solvent to be used is not particularly limited, and may be an amount capable of performing a reaction as uniform as possible, and it is not necessary to use a necessary amount or an appropriate amount or more. The amount of the solvent used in the reaction is 0.1 to 10 with respect to the number of moles of the reaction substrate.
A double liter is used, and an average usage amount is 0.5 to 3 liters. The reaction of the present invention can be carried out in the range of -80 ° C to the boiling point of the reaction solvent, and preferably -15 ° C to 150 ° C.

In the reaction for obtaining the general formula (III) from the general formula (I), the alcohol to be introduced is used as a solvent, or the alcohol to be introduced into an inert solvent with an acid such as benzene, toluene or chlorobenzene is used. The reaction is carried out at room temperature to the reflux temperature of the solvent in the presence of an acid catalyst using at least an equivalent amount. As described above, the compound represented by the general formula (I) is an intermediate from which an acrylic acid derivative (III) having a desired substituent R ₁₁ can be obtained by freely selecting a substituent of an alcohol to be used. Is a compound having high utility. In particular, when R ₂ is a hydrogen atom, the resulting acrylic acid derivative (III) hardly contains its stereoisomer,
In particular, it has a feature that only an E-form useful as an intermediate for pesticides is formed.

The reaction proceeds by a route of dealcoholation via an acetal derivative represented by the general formula (V). Therefore, when the alcohol is not used as a solvent, the reaction proceeds efficiently if the reaction is carried out while distilling off the alcohol in the reaction system outside the system. For the purpose of accelerating the acetalization reaction step, an orthoester represented by the general formula (IV) may be present in an amount of a catalytic amount or more.

The acetal compound (V) can be isolated by controlling the reaction conditions such as the reaction time or the reaction temperature. For example, the acetal compound (V) can be isolated by keeping the reaction temperature at around 60 ° C. and completing the reaction in a short time. The synthesis can also be carried out by using an orthoester in excess or as a solvent. Further, the compound can be synthesized by performing the reaction without distilling off the alcohol desorbed from the acetal compound (V) to the outside of the system. The acetal form (V) is an equivalent of the keto ester form (I), and exhibits not only the same reactivity as the keto ester form (I), but also the alkylation at the ester α-position which is usually difficult in the keto ester form (I). And the like, which is an intermediate that can be modified at the α-position, and can be said to be a highly useful compound also as an intermediate for other agricultural chemicals, medicines and the like.

From the general formulas (II) to R ₁₁ in the general formula (V)
Represents an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group. Specific examples include a methyl group, an allyl group, a cyclohexyl group, a phenyl group, and a 2-pyridyl group. In formula (IV), R ₁₂ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group. Specific examples include a hydrogen atom, a methyl group, an allyl group, a cyclohexyl group, a phenyl group, and a 2-pyridyl group. Specific examples of the compound represented by the general formula (IV) include methyl orthoformate and methyl orthoacetate.

The acid used in the reaction for converting the ketoester derivative (I) to the acrylic acid derivative (III) is not particularly limited and may be any of protonic acids and Lewis acids. Toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, aluminum chloride, zinc chloride, tin chloride, iron chloride, titanium chloride, alkoxy titanium chloride, alkoxy titanium, boron trifluoride diethyl ether complex, sulfuric acid, potassium monosulfate, etc. And particularly preferably p-
Toluenesulfonic acid, methanesulfonic acid and the like can be mentioned. Even when the isolated acetal compound (V) is used, the same reaction can lead to the acrylic acid derivative (III).

The acetal compound used in the present invention is not particularly limited as long as it is a compound represented by the general formula (V), or the acrylic acid derivative is a compound represented by the general formula (III). [Table 2001] to [Table 2003]).

[0024]

[Table 2001]

[0025]

[Table 2002]

[0026]

[Table 2003]

[0027]

The present invention will be described in more detail with reference to the following examples, but it should not be construed that the invention is limited thereto.

Example 1 To a solution of 2.28 g of titanium tetrachloride in 5 ml of methylene chloride, a solution of 1.27 g of trimethyl orthoformate in 5 ml of methylene chloride was added at room temperature. After stirring for 1 hour, the reaction solution was cooled to 0 ° C., and methyl 2-chloromethylphenylacetate
8 g of a 5 ml methylene chloride solution was added. After 30 minutes, a solution of 2.4 g of triethylamine in 5 ml of methylene chloride was added, and the mixture was further reacted for 1 hour. The reaction solution was diluted with 1N hydrochloric acid 24
The organic layer was dried with magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 1.70 g of target methyl 2- (2-chloromethylphenyl) -3-hydroxyacrylate (94% yield).

Example 2 A solution of 0.72 g of methyl formate in 5 ml of methylene chloride was added to a solution of 2.28 g of titanium tetrachloride in 5 ml of methylene chloride at room temperature. The reaction solution was cooled to 0 ° C., and a solution of 1.58 g of methyl 2-chloromethylphenylacetate in 5 ml of methylene chloride was added. After 30 minutes, 2.4 g of triethylamine
Was added, and the mixture was further reacted for 1 hour. The reaction solution was washed with 24 ml of 1N hydrochloric acid, and the organic layer was dried over magnesium sulfate. The solvent is distilled off under reduced pressure to give the desired 2- (2-chloromethylphenyl) -3-
1.72 g of methyl hydroxyacrylate was obtained (yield
96%). ¹ H-NMR (chemical shift value based on TMS) δ 3.74 (s, 3H, COOMe), 4.52
_{(S, 2H, CH 2)} , 7.06-7.41 (m, 5
H, Ar and CH), 12.0 (d, 1H, OH)

Example 3 To a solution of 2.00 g of aluminum chloride in 10 ml of methylene chloride was added 1.59 g of trimethyl orthoformate at 0 ° C. Subsequently, 1.98 g of methyl 2-chloromethylphenylacetate was added. 30 minutes later, triethylamine
33 g was added at 10 ° C. or lower, and the reaction was further performed for 1 hour.
The reaction solution was washed with 50 ml of 2N hydrochloric acid, and the aqueous layer was extracted twice with 10 ml of methylene chloride. The organic layer was dried with magnesium sulfate. The solvent was distilled off under reduced pressure to give an oil.
02 g were obtained. The target content of methyl 2- (2-chloromethylphenyl) -3-hydroxyacrylate is about 3
8%, and the remainder was raw material methyl 2-chloromethylphenylacetate (yield 34%).

Example 4 1.72 g of methyl 2- (2-chloromethylphenyl) -3-hydroxyacrylate was dissolved in 5 ml of methanol, and 0.2 g of p-toluenesulfonic acid monohydrate was added. This solution was refluxed for 6 hours, and then p-xylene 5m
1 was added. After refluxing for another 2.5 hours, 40 mmH
g of low boiling substances up to 30 ° C. were distilled off under reduced pressure. The system was returned to normal pressure and refluxed for about 1 hour. After cooling, 23.65 g of solution was obtained. According to HPLC analysis, this solution contained 4.08% of target methyl 2- (2-chloromethylphenyl) -3-methoxyacrylate (yield: 52).
%).

Example 5 To 1200 ml of monochlorobenzene, 342.0 g of titanium tetrachloride, 108.0 g of methyl formate, and 238.4 g of methyl 2-chloromethylphenylacetate were sequentially added at 1200 ° C. or less under a nitrogen stream. After 30 minutes, triethylamine 363.
6 g were added. After another 30 minutes, 76.8 g of methanol was added. 840 g of 15% hydrochloric acid and 600 of monochlorobenzene
ml was sequentially added to the reaction solution. The organic layer was washed twice with 12% hydrochloric acid, and about 600 ml of monochlorobenzene was distilled off under normal pressure to obtain 1564.5 g of a solution. 22.8 g of p-toluenesulfonic acid monohydrate and 76.9 of methanol were added to this solution.
g and trimethyl orthoformate (165.6 g), and
Heat at 0 ° C. for 5 hours. A distillation apparatus was attached to the reactor, and the solvent was distilled off for 3.5 hours while maintaining the internal temperature at 110 ° C. or lower. After cooling to room temperature, the reaction mixture was diluted with 2 N hydrochloric acid (479 m).
1, 479 ml of 5% aqueous sodium bicarbonate and 479 ml of water were washed in this order. Aqueous solution containing chlorobenzene about 2 under reduced pressure of 75 mmHg
After 40 ml was distilled off, 1488.6 g of a solution was obtained after cooling. According to HPLC analysis, this solution contained 17.08% of methyl 2- (2-chloromethylphenyl) -3-methoxyacrylate (88% yield).

The solvent was distilled off under reduced pressure from 532 g of this solution. 124 ml of ethyl acetate and 661 of n-hexane were added to the residue.
Then, the mixture was dissolved by heating to obtain a uniform solution. The solution was cooled to 4 to 6 ° C., and the precipitated crystals were separated by filtration. The crystals were washed with a mixed solvent of ethyl acetate / n-hexane and dried. 80.8 g of crystals of methyl 2- (2-chloromethylphenyl) -3-methoxyacrylate were obtained. ¹ H-NMR (chemical shift value based on TMS) δ 3.69 (s, 3H, COOCH ₃ ), 3.80
_{(S, 3H, OCH 3)} , 4.49 (s, 2H, C
_{H 2), 7.00-7.50 (m,} 4H, Ar), 7.
61 (s, 1H, CH)

Example 6 A solution of methyl 2- (2-chloromethylphenyl) -3-hydroxyacrylate in monochlorobenzene 137 prepared in the same manner as in Example 5 using 19.87 g of methyl 2-chloromethylphenylacetate. To 1.41 g, 1.44 g of methanesulfonic acid, 12.80 g of methanol, and 13.80 g of trimethyl orthoformate were added, and the mixture was reacted for 5.5 hours while maintaining the internal temperature at 67 to 68 ° C. After cooling the reaction solution, 5%
Washed with aqueous sodium bicarbonate and water. After the organic layer was dried over magnesium sulfate, the solvent was distilled off to obtain 29.11 g of a yellow oily substance. This was purified by silica gel chromatography (developing solvent: n-hexane / ethyl acetate) to give 2- (2-chloromethylphenyl) -3,3-dimethoxypropion as white crystals having a melting point of 63.5 to 64.5 ° C. 19.73 g of methyl acid was obtained (yield: 72%). ¹ H-NMR (chemical shift value based on TMS) δ 3.15 (s, 3H, OCH ₃ ), 3.50 (s,
3H, OCH ₃ ), 3.69 (s, 3H, COOC
_{H 3), 4.34 (d,} 1H, CH), 4.73 (d
_{d, 2H, CH 2),} 5.00 (d, 1H, CH),
7.25 to 7.61 (m, 4H, Ar)

Crystalline 2- (2-chloromethylphenyl)
2.73 g of methyl -3,3-dimethoxypropionate was dissolved in 10 ml of monochlorobenzene. 0.14 g of methanesulfonic acid was added to this solution and reacted at 110 ° C. for 40 minutes. After cooling, 17.66 g of solution was obtained. HP
According to LC analysis, methyl 2- (2-chloromethylphenyl) -3-methoxyacrylate was 12.1 in this solution.
6% was contained (89%).

Example 7 To a solution of 8.54 g of titanium tetrachloride in 15 ml of chlorobenzene, 2.70 g of methyl formate was added at 10 ° C. or lower.
Next, a solution of 7.29 g of methyl 2-bromomethylphenylacetate in 15 ml of chlorobenzene was added while maintaining the reaction solution at 10 ° C. or lower. After stirring at 10 ° C or lower for 30 minutes, 9.10 g of triethylamine was added at 10 ° C or lower.
The reaction was performed for 30 minutes. Chlorobenzene 15m in the reaction solution
1, 1.82 g of acetic acid and 12 ml of water were sequentially added. After stirring at room temperature for 1 hour, the organic layer was washed with 18 ml of 2N hydrochloric acid. The organic layer was concentrated and dried by distillation under reduced pressure. Add 7.5ml of chlorobenzene and add 30ml of chlorobenzene
It was adjusted to become. The thus obtained 2-
To a monochlorobenzene solution of methyl (2-bromomethylphenyl) -3-hydroxyacrylate, 0.43 g of methanesulfonic acid, 3.84 g of methanol, and 4.14 g of trimethyl orthoformate were sequentially added, and reacted at 55 ° C. for 4 hours.
A low-boiling substance was distilled off over 2 hours while keeping the internal temperature at 110 ° C. or lower by attaching a distillation apparatus to the reactor. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel chromatography (developing solvent: n-hexane / ethyl acetate) to give 2- (2-bromomethylphenyl) as white crystals having a melting point of 94 to 98 ° C. 4.05 g of methyl) -3-methoxyacrylate was obtained (yield 47%). ¹ H-NMR (chemical shift value based on TMS) δ 3.70 (s, 3H, OCH ₃ ), 3.83 (s, 3
H, COOCH ₃ ), 4.41 (s, 2H, CH ₂ ),
7.10 to 7.55 (m, 4H, Ar), 7.64
(S, 1H, CH).

[0037]

According to the method of the present invention, general formula (I)
Using a compound represented by the general formula (III), which is useful as a pharmaceutical or agricultural chemical intermediate in high yield and high selectivity without affecting a leaving group active for a nucleophile The compounds represented can be synthesized. The compound represented by the general formula (I) can be easily synthesized from inexpensive raw materials under known conditions. Further, the compound represented by the general formula (V) is a novel substance, and is a useful substance as another agricultural chemical or a pharmaceutical intermediate.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor: Hiroshi Ishii, Nakazawa-mura, Niigata Prefecture, Nakago-mura, Osamu Fujisawa 950 Japan Soda Corporation Nihongi Plant (72) Inventor: Hiroyuki Yazaki, Nakago-mura, Niigata Prefecture, Nakago-mura, Fujisawa 950, Soda, Japan F-term in Nihongi Plant Co., Ltd. (reference) 4H006 AA01 AA02 AB84 AC26 AC43 BA10 BA37 BA66 BA67 BJ50 BM10 BM30 BM72 BN10 BP10 BP30 BQ10 BR10 KA31 4H039 CA61 CD10 CD40

Claims (4)

[Claims] 1. A compound of the general formula (I) (Wherein, X represents a group which is eliminated when reacted with a nucleophile, and Y and Z may be the same or different and each represent a hydrogen atom, a halogen atom, an alkyl group, a cycloalkyl group,
Alkenyl group, alkynyl group, haloalkyl group, alkoxyalkyl group, aryl group, heteroaryl group, aralkyl group, alkoxy group, haloalkoxy group, allyloxy group, propargyloxy group, arylalkoxy group, aryloxy group, heteroaryloxy group, acyloxy group, an amino group, an arylazo group, an acylamino group, a nitro group, a cyano group, -CO ₂ R _3, -CONR _{4
R 5, -COR 6, -CR 7} = NR 8, or -N = CR
₉ represents R _10, and when Y and Z are adjacent to each other, forms an aliphatic or aromatic fused ring or a heterocyclic ring containing at least one hetero atom, and R ₁ represents an alkyl group, a cycloalkyl group,
Represents an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group, wherein R _{2 to} R ₇ , R ₉ and R ₁₀ may be the same or different, and may be a hydrogen atom, an alkyl group; Represents a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group, and R ₈ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group. Represents a group, a heteroaryl group, an aralkyl group, a cycloalkylalkyl group, or an alkoxy group. The ketoester derivative represented by the general formula (II): (Wherein, R ₁₁ represents an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkylalkyl group) and an acid catalyst. Reacting the compound with the general formula (III) (Wherein, X, Y, Z, R ₁ , R ₂ , and R ₁₁ represent the same groups as described above). 2. A compound of the general formula (I) (Wherein, X, Y, Z, R ₁ and R ₂ represent the same groups as described above).
I) Wherein R ₁₁ represents the same group as described above, and an alcohol represented by the general formula (IV): (In the formula, R ₁₂ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aryl group, an aralkyl group, or a cycloalkylalkyl group.)
Is reacted in the presence of an acid catalyst to form an orthoester represented by the general formula (III): (Wherein X, Y, Z, R ₁ , R ₂ , and R ₁₁ represent the same as described above). 3. A compound of the general formula (I) (X, Y, Z, R ₁ and R ₂ represent the same groups as described above). 4. A compound of the general formula (V) (Wherein, X, Y, Z, R ₁ , R ₂ , and R ₁₁ represent the same groups as described above).