JPH0931023A - Production of 2-methyl-4-oxo-2-cyclohexenecarboxylic acid ester and its new intermediate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject ester useful as an intermediate for physiological ly active substances, especially agrichemicals, by condensing an acetoacetate with formalin or paraformaldehyde and subsequently subjecting the obtained cyclohexanone derivative to dehydration and decarboxylation reactions. SOLUTION: (A) An acetoacetic acid ester of formula I (R is a linear or branched 1-6C alkyl, benzyl) is condensed with (C) formalin or paraformaldehyde in the presence of (B) an inorganic base (preferably calcium carbonate), and (D) the obtained cyclohexanone derivative of formula II or its tautomer is subjected to dehydration and decarboxylation reactions in the presence of (E) an inorganic salt (preferably magnesium dichloride hydrate or calcium dihalide hydrate) or a base (preferably sodium hydrate, potassium hydrate) to obtain the 2-methyl-4-oxo-2-cyclohexenecarboxylic acid ester of formula III.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing 2-methyl-4-oxo-2-cyclohexenecarboxylic acid ester. The 2-methyl-4-oxo-2-cyclohexenecarboxylic acid ester is useful as an intermediate for physiologically active substances, especially agricultural chemicals.

[0002]

2. Description of the Related Art A method of reacting acetoacetic acid ester and paraformaldehyde with an amine base such as piperidine as a catalyst to obtain 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-zircaponic acid diester is known. Is. (For example, Acta. Chem. Scan.
d. , 16 , 1329 (1962), Bull. So
c. Chim. France. , 843 (1958),
Justus. Liebig. Ann. Chem. 33
2 , 10 (1904)) Only ethyl ester and t-butyl ester are known for this compound. Further, as a method for obtaining 2-methyl-4-oxo-2-cyclohexenecarboxylic acid ester, 4-hydroxy-
A method in which 4-methyl-6-oxocyclohexane-1,3-dicarboxylic acid diester is dehydrated and decarboxylated with a metal alkoxide in an alcohol solvent (for example, Ch
em. Bcr. , 38 , 965 (1905)). In addition, acetoacetic acid ester and paraformaldehyde are reacted with piperidine as a catalyst to give 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-
A method is known in which dicarboxylic acid diester is obtained and then obtained by distillation or metal alkoxide. (J. Ch
em. Soc. Perkin I, 1837 (197)
9); Am. Chem. Soc. , 65 , 631
(1943)).

[0003]

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention
The reaction for obtaining -hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylic acid diester took a very long time of 2-3 days. Also, 2
The reaction for obtaining -methyl-4-oxo-2-cyclohexenecarboxylic acid ester has a low yield of 50 to 60%, and a large amount of industrial waste is produced after distillation, which is an industrial problem. In the dehydration and decarboxylation reaction, there is a method of using an inorganic acid such as sulfuric acid or hydrochloric acid, but the selectivity is low, and 3-methyl-2-cyclohexenone in which two esters are removed is produced, so that the yield is low. J. C. S. Perkin I,
In the method of 1837 (1979), a decarboxylation reaction occurs during distillation, so that the yield is low and the desired product with high purity cannot be obtained.

[0004]

As a result of repeated studies to solve the above-mentioned problems, 2-methyl-4-oxo-2-cyclohexenecarboxylic acid ester and its intermediate 4-hydroxy-4-methyl A method for producing -6-oxocyclohexane-1,3-dicarboxylic acid diester in good yield was found. That is, the present invention uses the formula

[0005]

Embedded image

(Wherein R is linear or branched C _1- )
A C ₆ alkyl group or a benzyl group is shown. ) 2-methyl-4-oxo-2-cyclohexenecarboxylic acid ester represented by

[0007]

[Chemical 6]

(Wherein R is a linear or branched C _1-
A C ₆ alkyl group or a benzyl group is shown. ) Is represented by 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylic acid diester. The compound of formula (1) can be produced as follows. That is, the expression

[0009]

[Chemical 7]

(Wherein R is linear or branched C _1-
A C ₆ alkyl group or a benzyl group is shown. ) The acetoacetic acid ester represented by) is condensed with paraformaldehyde or formalin in the presence of an inorganic base to give an intermediate.

[0011]

Embedded image

(Wherein R is linear or branched C _1- )
A C ₆ alkyl group or a benzyl group is shown. ), A cyclohexanone derivative or a tautomer thereof can be produced, followed by reaction with an inorganic salt or a base, and dehydration and decarboxylation reactions without isolation to produce the compound.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The amount of acetoacetic acid ester used in the above reaction is usually 2 equivalents to 4 equivalents with respect to formalin or paraformaldehyde, and preferably 2.
It is 2 equivalents to 3 equivalents.

With respect to the condensation step, examples of the inorganic base used include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate and the like, with potassium carbonate and sodium carbonate being preferred. . The amount of the inorganic base is usually 0.1 equivalent to 2 equivalents, preferably 0.1 equivalent to 1 equivalent relative to formalin or paraformaldehyde. Also,
The addition can be performed twice before and after the addition of formalin to control runaway reaction due to heat generation.

The formalin dropping temperature or paraformaldehyde addition temperature is usually -20 ° C to 120 ° C, preferably -10 ° C to 70 ° C.

In the condensation step of the compound of the formula (2) with formalin or the like, the solvent used is benzene,
Examples of the solvent include aromatic solvents such as toluene, xylene and chlorobenzene, alcohol solvents such as methanol and ethanol, and halogen solvents such as dichloromethane.

When an inorganic salt is used in the dehydration and decarboxylation step, the inorganic salt is preferably a magnesium salt such as magnesium chloride hydrate, a calcium salt such as calcium chloride hydrate, or sodium chloride. Examples thereof include sodium salts, lithium salts such as lithium chloride, and potassium salts such as potassium chloride. The amount is the formula (3)
The amount is usually 0.1 equivalent to 2 equivalents, preferably 0.2 equivalent to 1 equivalent relative to the compound of.

When the above-mentioned inorganic salt is used, dehydration and decarboxylation reactions may be carried out without a solvent, but may be carried out in a dipolar solvent or an inorganic acid water. As the dipolar solvent, N-methyl-
2-pyrrolidinone, N, N-dimethylacetamide,
N, N-dimethylformamide, ethylene glycol,
Dimethyl sulfoxide, hexamethylphosphoric triamide and the like can be mentioned, and the amount used is usually 0.001 L / mol to 3.0 L / mol, preferably 0.01 L / mol to the compound of the formula (3). 1.5 L / mol
It is. Examples of the inorganic acid include hydrochloric acid water, sulfuric acid water and the like, and the amount used is usually 0.001 with respect to the compound of the formula (3).
Equivalent to 0.5 equivalent, preferably 0.01 equivalent
It is 0.2 equivalent.

When an inorganic salt is used, the reaction temperature is usually 5
The temperature is 0 ° C to 180 ° C, preferably 70 ° C to 160 ° C.

When a base is used in the dehydration and decarboxylation step, examples of the base include sodium hydroxide, potassium hydroxide and potassium carbonate, and sodium hydroxide and potassium hydroxide are preferable. The amount of base is 0.2 equivalent to 3 equivalents relative to the compound of formula (3), preferably 1
Equivalent to 2 equivalents.

When a base is used in the dehydration and decarboxylation step, examples of the solvent to be used include aromatic solvents such as toluene and xylene, alcohol solvents such as methanol and ethanol, or water, and preferably. It is water. The reaction temperature is generally 0 ° C to solvent reflux temperature, preferably 50 ° C to solvent reflux temperature.

As the compound of the formula (1) obtained in the present invention, R is, for example, methyl group, ethyl group, n-propyl group,
Examples thereof include i-propyl group, n-butyl group, t-butyl group, n-pentyl group, 1,1-dimethylpropyl group, 2,2-diethyl-1-methylpropyl group and n-hexyl group.

These compounds are converted into chromanic acid derivatives by the following reaction formula.

[0024]

Embedded image

In addition, Jour. Indian. Che
m. Soc. , Vol. 45, no. 3,200 (19
It can also be converted to a chroman acid derivative by the following reaction formula described in 68).

[0026]

Embedded image

This chroman derivative is used as a raw material for a hydrazine compound having a high insecticidal activity against the pests of Lepidoptera and Hemiptera known in EP 049634.

[0028]

The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

Example 1 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: Ethyl acetoacetate (1560 g, 12
mol, 2.4 equivalents) to potassium carbonate (138.2 g,
1 mol) was added and heated to 50 ° C. While maintaining this temperature, 35% formalin (429 g, 5 mol) was added dropwise, and after completion of the addition, the mixture was stirred at 50 ° C. for 30 minutes. After that, the reaction liquid was cooled to 30 ° C., and after liquid separation, potassium carbonate (138.2 g, 1 mol) was added again, and the mixture was stirred at 70 ° C. for 2 hours. Next, the reaction solution was cooled to 50 ° C., 15% hydrochloric acid water (520 g) was added for neutralization, and the layers were separated. The organic layer was used as a yellow oil to obtain 1636 g. Next, magnesium chloride hexahydrate (203 g, 1 mol) was added, and the mixture was heated to 140 ° C. and stirred for 7 hours while removing low-boiling distillate. Then, the reaction solution was cooled to 30 ° C., water (200 g) was added, and the solution was separated. Vacuum distillation of the organic layer (130-138 ° C / 9mm
Hg) to obtain the desired product (753.9 g, purity 95.6%, yield 79.1%).

¹ H-NMR (300 MHz, CDCl ₃ ) (ppm) 1.30 (t, 3H, J = 7.0 Hz) 2.02 (s, 3H) 2.1 to 2.4 (3H) 2. 5-2.6 (m, 1H) 3.26 (s, 1H) 4.21 (q, 2H, J = 7.0Hz) 5.96 (s, 1H) Example 2 4-hydroxy-4-methyl Preparation of diethyl-6-oxocyclohexane-1,3-dicarboxylate: Add potassium carbonate (13.8 g, 0.1 mol) to ethyl acetoacetate (156.2 g, 1.2 mol, 2.4 eq) and add 5
Heated to 0 ° C. While maintaining this temperature, 35% formalin (42.9 g, 0.5 mol) was added dropwise, and after completion of the addition, the mixture was stirred at 50 ° C. for 30 minutes. After that, the reaction solution was cooled to 30 ° C., and after liquid separation, potassium carbonate (13.8 g,
0.1 mol) was added and the mixture was stirred at 70 ° C. for 2 hours. Next, the reaction liquid was cooled to 50 ° C., 8% aqueous sulfuric acid (130 g) was added to neutralize, and the liquid was separated. 15 as the target oil
5.6 g was obtained. (4-hydroxy-4-methyl-6-
Oxocyclohexane-1,3-dicarboxylate diethyl, purity 68.5%, yield 78.3%, 2-methyl-4.
Ethyl -oxo-2-cyclohexenecarboxylate, purity 10.3%, yield 17.6%) ¹ H-NMR (300 MHz, CDCl ₃ ) (ppm) 1.29 (t, 3H, J = 7.1 Hz). 1.31 (t, 3H, J = 7.1 Hz) 1.34 (s, 3H) 2.2-2.3 (m, 1H) 2.36 (dd, 1H, J = 2.4, 14. 4 Hz) 2.6 to 2.7 (m, 2H) 2.86 (dd, 1H, J = 3.5, 13.5 Hz) 3.40 (dd, 1H, J = 5.5, 12.3 Hz) 3.61 (d, 1H, J = 2.2 Hz) 4.15 to 4.25 (m4H) When the temperature at the time of dropping formalin was changed and the same operation as in Example 2 was performed, the following results were obtained. Was given. When the dropping temperature is 70 ° C. or lower, the target product can be obtained in good yield.

[0031]

[Table 1]

Example 6 Preparation of isopropyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: isopropyl acetoacetate (8
Potassium carbonate (34.6 g, 0.25 mol) was added to a toluene solution (6.4 g, 0.6 mol, 2.4 eq) of toluene (100 ml, 0.4 L / mol), and the mixture was cooled to 5 ° C. While maintaining this temperature, 92% paraformaldehyde (8.16 g, 0.25 mol) was added, and the mixture was stirred at this temperature for 2 hours. After that, stop cooling and heat to 70 ° C. 3
Stirred for hours. Next, the reaction solution was cooled to 20 ° C., 10% hydrochloric acid water (180 ml) was added to neutralize, and the layers were separated. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give a yellow oil (80.8 g). Then N-methyl-2-pyrrolidinone (75 ml,
0.3 L / mol), magnesium chloride hexahydrate (5
0.8 g, 0.25 mol) was added, and the mixture was heated to 130 ° C. and stirred for 5 hours. Then, the reaction solution was cooled to 20 ° C., 5% hydrochloric acid (100 ml), ethyl acetate (100 m)
l) was added and the layers were separated. Wash the organic layer with saturated saline,
After drying over anhydrous magnesium sulfate, the solvent was removed under reduced pressure to obtain 53.2 g of a brown oil. This oil was distilled under reduced pressure (89 to 92 ° C / 1 mmHg) to obtain the desired product (41.1
g, purity 98.8%, yield 78.9%).

¹ H-NMR (300 MHz, CDCl ₃ ) (ppm) 1.27 (d, 6H, J = 6.4 Hz) 2.02 (s, 3H) 2.2-2.4 (3H) 2. 5-2.6 (m, 1H) 3.23 (t, 1H, J = 5.5Hz) 5.07 (sep, 1H, J = 6.4Hz) 5.96 (s, 1H) of acetoacetic acid ester When the same operation was performed by changing the amount, the results shown in Table 2 were obtained. When the amount of acetoacetic acid ester is 2.2 equivalents or more relative to formaldehyde, the target product can be obtained in good yield.

[0034]

[Table 2]

Example 10 Preparation of isopropyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: 4-hydroxy-4-methyl-
Magnesium chloride hexahydrate (6.10 g, 0.03 mol) was added to diisopropyl 6-oxocyclohexane-1,3-dicarboxylate (9.01 g, 0.03 mol), and the mixture was stirred at 130 ° C for 4.5 hours. Then, the reaction solution was cooled to room temperature, 10% hydrochloric acid (50 ml) and ethyl acetate (50 ml) were added, and the layers were separated. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give the desired product (6.36 g, purity 75.3%, yield 81.4%).

Example 11 Preparation of isopropyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: 4-hydroxy-4-methyl-
6-oxocyclohexane-1,3-dicarboxylate diisopropyl (9.01 g, 0.03 mol) in N-methyl-2-pyrrolidinone (0.3 ml, 0.01 L / mo)
l), and then calcium chloride dihydrate (4.41
g, 0.03 mol) was added, and the mixture was stirred at 130 ° C. for 4 hours. Then, the reaction solution was cooled to room temperature, and 10% hydrochloric acid (5
0 ml) and ethyl acetate (50 ml) were added and the layers were separated. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to remove the desired product (6.31 g,
The purity was 77.1% and the yield was 82.7%).

Example 12 Preparation of isopropyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: 4-hydroxy-4-methyl-
N-Methyl-2-pyrrolidinone (9 ml, 0.3 L / mol) was added to diisopropyl 6-oxocyclohexane-1,3-dicarboxylate (9.01 g, 0.03 mol), and then magnesium chloride hexahydrate (6 .10 g,
0.03 mol) was added and the mixture was stirred at 130 ° C. for 1.5 hours. Then, the reaction solution was cooled to room temperature, and 10% hydrochloric acid (5
0 ml) and ethyl acetate (50 ml) were added and the layers were separated. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to remove the desired product (6.59 g,
The purity was 80.9% and the yield was 90.7%).

Example 13 Preparation of isopropyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: 4-hydroxy-4-methyl-
2% Hydrochloric acid water (1 ml, 0.6 mmol) was added to diisopropyl 6-oxocyclohexane-1,3-dicarboxylate (9.01 g, 0.03 mol), and then magnesium chloride hexahydrate (6.10 g, 0. (03 mol) was added, and the mixture was stirred at 110 ° C. for 3.5 hours. Then, the reaction solution was cooled to room temperature, 10% hydrochloric acid (50 ml) and ethyl acetate (50 ml) were added, and the layers were separated. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give the desired product (6.35 g, purity 67.2%, yield 72.5%).

Example 14 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: Diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate (8.17 g, 0. Magnesium chloride 6 in (03 mol)
Add the hydrate (6.10 g, 0.03 mol) and add 130
Stirred at C for 5 hours. Then, the reaction solution was cooled to room temperature, 10% hydrochloric acid (10 ml), ethyl acetate (50 ml)
Was added and liquid separation was performed. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure to obtain the desired product (5.67 g, purity 82.3%, yield 85.4%).
I got

Example 15 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate (68.08 g, 0. Magnesium chloride hydrate (15.25 g, 0.075 mol) was added to (25 mol), and then N-methyl-2-pyrrolidinone (7.5 ml, 0.
(03 L / mol) was added, and the mixture was stirred at 130 ° C to 136 ° C for 5 hours. Then, the reaction solution was cooled to room temperature, 10% hydrochloric acid (70 ml) and ethyl acetate (70 ml) were added for extraction. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to remove the desired product (40.
67 g, purity 79.8%, yield 80.7%) were obtained.

Example 16 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: Diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate (68.85 g, 0.85 g). Magnesium chloride hexahydrate (10.17 g, 0.05 mol) was added to 25 mol), and then 2% hydrochloric acid water (7 ml, 0.005 mol) was added,
The mixture was stirred at 108 ° C to 112 ° C for 3.5 hours. Then, the reaction solution was cooled to room temperature, water (50 ml) and ethyl acetate (70 ml) were added for extraction. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give the desired product (45.57 g, purity 73.0%, yield 73.0%).

Example 17 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate (8.17 g, 0. Calcium chloride dihydrate (4.41 g, 0.03 mol) to
-Methyl-2-methylpyrrolidinone (0.3 ml, 0.
(01 L / mol) was added, and the mixture was stirred at 130 ° C. for 10 hours. Then, the reaction solution was cooled to room temperature, and water (50 m
l) and ethyl acetate (50 ml) were added for extraction. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give the desired product (5.63 g, purity 80.0%, yield 82.4%).

Example 18 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: Diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate (5.44 g, 0.40 g). While maintaining a mixed solution of 02 mol) and water (10 ml) at 20 ° C to 30 ° C, 48% sodium hydroxide (1.67 g, 0.02 mol) was added dropwise. Then, it heated at 75 degreeC-80 degreeC, and stirred for 2 hours. After that, the reaction solution was cooled to room temperature, neutralized with 5% hydrochloric acid (6 ml), and extracted with ethyl acetate (30 ml). The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give the desired product (3.54 g,
Purity 72.8%, yield 70.7%) was obtained.

Example 19 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate (5.44 g, 0.40 g). While maintaining a mixed solution of 02 mol) and water (10 ml) at 20 ° C to 30 ° C, 50% potassium hydroxide (2.24 g, 0.02 mol) was added dropwise. Then, it heated at 75 degreeC-80 degreeC, and stirred for 2 hours. After that, the reaction solution was cooled to room temperature, neutralized with 5% hydrochloric acid (6 ml), and extracted with ethyl acetate (30 ml). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to remove the desired product (3.50 g,
Purity 75.0%, yield 72.0%) was obtained.

For comparison, dehydration and decarboxylation of diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate were carried out under other conditions. (Reference examples 1 and 2).

Reference Example 1 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate (1.0 g, 3. 7 mol) to piperidine (62.9 m
g, 0.74 mmol) was added, and the mixture was stirred at 100 ° C. for 5 hours. The product (0.92 g) was analyzed by gas chromatography, and the purity was only 6.2%. (Yield 8.5%).

Reference Example 2 Preparation of ethyl 2-methyl-4-oxo-2-cyclohexenecarboxylate: diethyl 4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate (2.0 g, 7. Toluene (1.5m
g, 0.2 L / mol), then potassium carbonate (1.02 g, 7.4 mmol), and added at 110 ° C. for 3
Stirred for hours. Then, the reaction solution was cooled to room temperature, and water (5
0 ml) was added, and the mixture was extracted with toluene (50 ml). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to remove the desired product (1.
30 g, purity 54.5%, yield 53.1%) were obtained.

Results of Examples 10 to 19 and Reference Examples 1 and 2
From the results, the method of Example showed better results than the method of Reference Example.

Example 20 Preparation of diisopropyl 4,6-dihydroxy-4-methyl-6-cyclohexene-1,3-dicarboxylate: A solution of isopropyl acetoacetate (288.8 g, 2.0 mol) in toluene (400 ml, 0. Potassium carbonate (138.2 g, 1.0 mol) was added to 2 L / mol), and the temperature was 5 ° C.
And cooled. Paraformaldehyde (33.4 g, 1.0 mol) was added while maintaining this temperature, and the mixture was stirred at this temperature for 3 hours. Thereafter, the cooling was stopped, and the mixture was stirred at 30 ° C. for 2.5 hours and then at 65 ° C. for 4 hours. Next, the reaction solution was cooled to 20 ° C., 10% hydrochloric acid water (800 ml) was added to neutralize, and the layers were separated. The organic layer was washed successively with water (300 ml) and saturated brine (300 ml), dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give a pale yellow oil 291.8 g. This was purified by silica gel column chromatography (n-hexane-ethyl acetate system) to give the desired product (enol system) as white crystals (26
1.0 g, gas chromatographic purity 93%, yield 81.1%, melting point 54-55 ° C.).

¹ H-NMR (300 MHz, CDCl ₃ ) (ppm) 1.26 (d, 6 H, J = 6.5 Hz) 1.29 (d, 6 H, J = 6.5 Hz) 1.31 (s, 3H) 2.25 to 2.55 (m, 5H) 3.50 (d, 1H, J = 6.1 Hz) 5.10 (sep, 2H, J = 6.1 Hz) 12.3 (s, 1H) 4-Hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylic acid was reacted in the same manner as in Example 20 except that 2.0 mol of methyl acetoacetate was used instead of 2.0 mol of isopropyl acetoacetate. Dimethyl (keto form) was obtained as white crystals (melting point: 76-78 ° C). (Yield 38%) ¹ H-NMR (300 MHz, CDCl ₃ ) (ppm) 1.34 (s, 3H) 2.2 to 2.3 (m, 1H) 2.37 (dd, 1H, J = 2) .4, 15.7 Hz) 2.62 (d, 1H, J = 14.2 Hz) 2.73 (ddd, 1H, J = 12.8, 12.8, 1
2.8 Hz) 2.84 (dd, 1H, J = 3.3, 12.9 Hz) 3.41 (dd, 1H, J = 6.1, 12.9 Hz) 3.51 (d, 1H, J = 2.6 Hz) 3.76 (s, 3H) 3.78 (s, 3H)

[0051]

Industrial Applicability According to the present invention, a raw material of a hydrazine derivative having a high insecticidal activity can be obtained in a high yield.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location C07C 67/327 C07C 67/327 67/343 67/343 // C07B 61/00 300 C07B 61/00 300 (72) Inventor Tetsuya Toya 1090 Kamiochiai, Yono-shi, Saitama Nippon Kayaku Yonosha Home (72) Inventor Shuji Kawata 331-61, Oina, Kita Adachi-gun, Saitama Prefecture

Claims (16)

[Claims] (1) Formula (1) (Wherein R represents a C ₁ -C ₆ alkyl group which may be linear or branched or a benzyl group), and a method for producing a 2-methyl-4-oxo-2-cyclohexenecarboxylic acid ester represented by the formula [Chemical 2] (Wherein R represents a C ₁ -C ₆ alkyl group which may be linear or branched or a benzyl group) and is condensed with formalin or paraformaldehyde in the presence of an inorganic base. , The formula: (Wherein R represents a C ₁ -C ₆ alkyl group which may be linear or branched or a benzyl group), or a tautomer thereof is produced, and then in the presence of an inorganic salt. Alternatively, the production method is characterized in that dehydration and decarboxylation are carried out in the presence of a base. 2. Regarding the production of the cyclohexanone derivative represented by the formula (3) or a tautomer thereof, the acetoacetic acid ester represented by the formula (2) is condensed with formalin or paraformaldehyde in the presence of an inorganic base. A manufacturing method characterized by that. 3. A process for producing a compound represented by the formula (1) from a cyclohexanone derivative represented by the formula (3) or a tautomer thereof, in the presence of an inorganic salt or a base, dehydration and decarboxylation. The manufacturing method characterized by performing. 4. The method according to claim 1, wherein in the condensation reaction, the amount of acetoacetic acid ester is 2 equivalents to 4 equivalents with respect to formalin or paraformaldehyde. 5. The method according to claim 1, wherein the inorganic base is potassium carbonate in the condensation reaction. 6. The method according to claim 1, wherein in the condensation reaction, the amount of the inorganic base is 0.1 equivalent to 1 equivalent with respect to formalin or paraformaldehyde. 7. The method according to any one of claims 1, 2, 4, 5 and 6, wherein in the condensation reaction, the inorganic base is added separately before and after the addition of formalin. . 8. The method according to claim 1, wherein in the condensation reaction, the formalin dropping temperature is −10 ° C. to 70 ° C. 9. In the dehydration and decarboxylation reaction, when an inorganic salt is used, the inorganic salt is magnesium chloride hydrate or calcium chloride hydrate.
The method according to any one of 6, 7, and 8. 10. The dehydration / decarboxylation reaction, when an inorganic salt is used, the reaction temperature is 70 ° C. to 160 ° C., and the reaction temperature is 70 ° C. to 160 ° C. the method of. 11. The method according to any one of claims 1, 3, 4, 5, 6, 7, 8, 9 and 10, wherein a dipolar solvent is added when an inorganic salt is used in dehydration and decarboxylation reactions. The method described in. 12. The water and the inorganic acid are added when an inorganic salt is used in the dehydration and decarboxylation reactions, which are characterized in that: The method described in any one of. 13. A solvent used when a base is used in dehydration and decarboxylation reactions is toluene, xylene, methanol, ethanol or water.
9. The method according to any one of 8 and 8. 14. The method according to any one of claims 1, 3, 4, 5, 6, 7, 8 and 13, wherein when a base is used in the dehydration and decarboxylation reaction, the base is sodium hydroxide or potassium hydroxide. That way. 15. The method according to claim 1, wherein the reaction temperature is 50 ° C. to the solvent reflux temperature when a base is used in the dehydration and decarboxylation reactions. Either way. 16. The formula: (In the formula, R represents a linear or branched C ₁ -C ₆ alkyl group or a benzyl group, excluding an ethyl group and a t-butyl group.), And a cyclohexanone derivative and a tautomer thereof.