JPH07179452A - Dihydrochroman carboxylic acids and their production - Google Patents

Abstract

PURPOSE:To provide a new dihydrochroman compound useful as an intermediate for producing a 1-alkyl-1,2-dibenzoylhydrazine having insecticidal activity. CONSTITUTION:A compound of formula I (R is a 1-6C lower alkyl except ethyl), e.g. isopropyl 5-methyl-7,8-dihydro-6-chromancarboxylate. The compound of formula I is obtained by reacting a compound of formula II with a compound of formula III (X and Y each is a halogen) in the presence of a base such as NaOH or KOH in a two phase system consisting of an nonaqueous solvent such as dichloromethane, (di)chlorobenzene, toluene or xylene and water.

Description

Detailed Description of the Invention

[0001]

The present invention relates to an intermediate useful in the process for producing 1-alkyl-1,2-dibenzoylhydrazines known to have insecticidal activity (JP-A-5-163266). The present invention relates to a dihydrochromanic acid which is a precursor of chromanic acid and a method for producing the same. The hydrazines are useful as agricultural insecticides.

[0002]

2. Description of the Related Art A method is known in which a cyclohexenone ester and 1,3-dibromopropane are reacted with potassium t-butoxide in t-butanol to obtain a dihydrochromancarboxylic acid ester. (J. Indian
Chem. Soc. , 45, 200 (1968)) Also, 4-oxo-2-methyl-2-cyclohexenecarboxylic acid ethyl ester is known as a Hagemanns ester. (J. Amer. Chem. Soc., 6
5,631 (1943), J. C. S. Prekin
1,602,1972)

[0003]

From the industrial point of view, the prior art is t-butoxide, which is difficult to handle and expensive in terms of danger, and a solvent (t-butoxide) which is water-soluble and difficult to recover.
Butanol) is used, and a spiro compound that is difficult to purify is by-produced, which is not an industrial production method. For this reason, there has been a demand for an industrially advantageous production method that uses an easily recoverable solvent and is inexpensive and has a good yield.

[0004]

The present invention has the following formula (2).

[0005]

[Chemical 6]

(In the formula, R represents a C ₁ -C ₆ lower alkyl group.) 4-oxo-2-methyl-2
-Cyclohexenecarboxylic acid ester and the following formula (3)

[0007]

[Chemical 7]

## STR1 ## wherein X and Y represent a halogen atom, and a halogen compound represented by the following formula (1) is prepared.

[0009]

[Chemical 8]

The present invention relates to an industrially advantageous process for producing 5-methyl-7,8-dihydro-6chromanate represented by the formula (wherein R represents a C ₁ -C ₆ lower alkyl group). .

Specifically, (A) a method of carrying out a reaction in the presence of a base in a two-phase system of water and a non-water-soluble solvent, and (B)
It is intended to provide a method for performing a reaction in a polar aprotic solvent in the presence of a base. That is, according to this production method, an inexpensive base such as sodium hydroxide or potassium carbonate can be used and a dihydrochroman acid ester can be obtained in good yield.

The non-aqueous solvent used is, for example, dichloromethane, chloroform, 1,1,1-trichloroethane,
Examples thereof include halogenated hydrocarbons such as tetrachloroethylene, chlorobenzene and dichlorobenzene, and hydrocarbons such as methyl butyl ketone, acetic acid t-butyl ester, xylene and toluene. Preferred are dichloromethane, chlorobenzene, dichlorobenzene, toluene and xylene. As the polar aprotic solvent used,
N-methylpyrrolidinone (NMP), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N, N-dimethylimidazolinone (D
MI), dimethyl sulfoxide (DMSO) and the like. Preferred are NMP and DMAC. The amount of the solvent used is 200 with respect to the compound of the formula (2).
-1500 ml / mol, preferably 400-1
It is 000 ml / mol.

The bases used include alkali metal and alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, and alkali metal and alkaline earth metal hydroxides such as sodium carbonate, potassium carbonate and calcium carbonate. I can give you a carbonate. In the case of the method using water and a non-water-soluble solvent (method A), sodium hydroxide and potassium hydroxide are preferable. In the case of the method using a polar aprotic solvent (method B), potassium carbonate and sodium carbonate are preferable. The amount of the base used is 2-8 eq / mol, preferably 2-5 eq / mol, based on the compound of formula (2). The concentration of the base may be arbitrary, but it is preferably as high as possible in consideration of productivity and reaction rate. For example, in the method (A), when sodium hydroxide is used, the higher the concentration of the base, the faster the reaction rate and the better the productivity per reactor. In the case of sodium hydroxide, it may be added as a solid (granular to finely granular) without using water.

In the method (A), the reaction rate can be increased by adding a phase transfer catalyst. The phase transfer catalyst used is tetrabutylammonium bromide, tetramethylammonium chloride, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, benzyltributylammonium chloride, methyltrioctylammonium chloride, methyltriphenylphosphonium bromide, amyltriphenylphosphonium. It is a ammonium bromide, preferably tetrabutylammonium bromide and methyltrioctylammonium chloride. The amount of the phase transfer catalyst added is 0.01 to 20% with respect to the compound represented by the formula (2).
It is preferably an equivalent amount.

In the method (B), it was found that the addition of potassium iodide improves the yield. The amount of potassium iodide added is 0.05 to 1.0 equivalent, preferably 0.1 to 1.0, relative to the compound of formula (2).
It is 0.3 equivalent.

The 1,3-dihalogenopropane represented by the formula (3) used for alkylation and cyclization is 1,3-dichloro, 1,3-dibromo, 1,3-diiodo, 1-chloro-3-bromo, 1-chloro-3. -Iodo, 1-bromo-3-iodopropane. 1-chloro-3-bromo and 1-chloro-3-iodopropane are preferred, and 1-chloro-3-bromopropane is more preferred. The amount of 1,3-dihalogenopropane used is 1-5 eq / mol, preferably 1-1.5 eq / mol in the (A) method, and 1-3 eq in the (B) method.
q / mol.

The reaction temperature is 0 to 10 in the method (A).
It may be 0 ° C, but preferably 0 to 60 ° C. In method (B), the boiling point of the solvent is preferably 50 to 90 ° C., more preferably 90 to 170 ° C.

Specific examples of the substituents of the compounds represented by the formulas (1) and (2) are as follows: R is linear alkyl such as methyl, ethyl, propyl and isopropyl, t-butyl, s.
Examples include branched alkyl groups such as ec-butyl. Here, R is a 4-oxo-2-methyl-2-cyclohexenecarboxylic acid ester represented by the formula (2) in which a methyl group, an ethyl group and a t-butyl group are removed, and R is represented by a formula (1) in which the ethyl group is removed. The 5-methyl-7,8-dihydro-6-chromanate is a compound not described in the literature.

The compound of formula (1) can be converted to 5-methyl-6-chromanic acid by oxidizing it to give 5-methyl-6-chromanic acid ester, and then by hydrolyzing the ester group. The compound is disclosed in JP-A-5-16.
It can be used as a raw material of a dibenzoylhydrazine compound having an excellent insecticidal activity against pests such as Lepidoptera, Hemiptera and other insects described in 3266.

[0020]

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

Example 1 Preparation of ethyl 5-methyl-7,8-dihydro-6-chromancarboxylate Ethyl 4-oxo-2-methyl-2-cyclohexenecarboxylate 80 g (purity 95%, 0.418 mol), 1
-Bromo-3-chloropropane 69g (0.44mo
l) and 6.7 g of tetrabutylammonium bromide
(0.02 mol) was dissolved in 300 ml of dichloromethane, and stirred at 20-30 ° C. with 48% caustic soda water 134.
g was added dropwise. After completion of the dropping, the mixture was stirred at 40 ° C. for 1 hour, and 80 ml of water was added at 10 ° C. or lower under ice cooling. After separating the aqueous layer,
The organic layer was washed with water, dried (magnesium sulfate) and concentrated to obtain 111.3 g of a light brown oil. The purity of this product was 55.1% (gas chromatography, internal standard method), and the pure yield was 66%. By distilling this light brown oil under reduced pressure, the desired ethyl 5-methyl-7,8-dihydro-6-chromancarboxylate 5 was obtained.
5.1 g was obtained. B. p. 130-135 ℃ / 2mmH
g, melting point: 68-9 ° C. H-NMR σ (ppm)
4.17 (2H, q, J = 7Hz), 4.01 (2H,
t, J = 4.6 Hz), 2.45 (2H, m), 2.1
7 (3H, s), 2.3-1.8 (6H, M)

Example 2 Preparation of isopropyl 5-methyl-7,8-dihydro-6-chromancarboxylate 40 g isopropyl 4-oxo-2-methyl-2-cyclohexenecarboxylate (purity 94.8%, 0.193 m)
ol), 31.9 g of 1-bromo-3-chloropropane
(0.203 mol) and 1.25 g (0.0039 mol) of tetrabutylammonium bromide were dissolved in 97 ml of chlorobenzene, and 42.7 g of 40% caustic soda water was added dropwise at 30 ° C under stirring. After completion of dropping, the mixture was stirred at 40 ° C for 6 hours, and 40 ml of water was added at 10 ° C or lower under ice cooling. After separating the aqueous layer, the organic layer is washed with water, dried (magnesium sulfate), and concentrated to give 70.2 g of a light brown oil.
Got By distilling this light brown oil under reduced pressure, 27.3 g of the target isopropyl 5-methyl-7,8-dihydro-6-chromancarboxylate was obtained. B. p.
130-135 ℃ / 1,5mmHg.

Example 3 Preparation of methyl 5-methyl-7,8-dihydro-6-chromancarboxylate 10 g of methyl 4-oxo-2-methyl-2-cyclohexenecarboxylate (purity 83%, 0.0493 mol),
Bromochloropropane 9.3 g (0.0591 mol)
And tetrabutylammonium bromide 0.9g
(2.8 mmol) was dissolved in 50 ml of dichloromethane, and 19 g of 48% caustic soda water was added at 20-25 ° C. with stirring.
Was dripped. After completion of dropping, the mixture was stirred at 25 ° C for 1 hour and at 40 ° C for 2 hours, and then 20 ml of ice-cooled water was added. After separating the aqueous layer, the organic layer was washed with water, dried (sodium sulfate) and concentrated to obtain 10.1 g of a light brown oil. The oil solidified at room temperature and was recrystallized from MeOH to give 6 g of white crystals. Net yield 58%. M. P. 90-9
1 ° C. H-NMR σ (ppm) 4.00 (2H, t,
J = 5 Hz), 3.71 (3 H, s), 2.45 (2
H, m), 2.17 (3H, s), 2.3-1.8 (6
H, m)

Example 4 Preparation of 5-methyl-7,8-dihydro-6-chromanic acid ethyl ester: 50 g of ethyl 4-oxo-2-methyl-2-cyclohexenecarboxylate (purity 92.4%, 0.254mo)
l) 120 g of 1-bromo-3-chloropropane, NM
P232g and 4.2 g of potassium iodide were charged and heated to 140 ° C under a nitrogen stream while stirring. 84.3 g of powdery potassium carbonate was added, and the mixture was stirred at 140 ° C. for 2 hours. The reaction mixture was cooled to 5 ° C or lower and then filtered. The residue was washed with ethyl acetate, and the obtained filtrate was washed with saturated brine / water (1: 1). The ethyl acetate solution was dried over magnesium sulfate and then concentrated to give a light brown oil (87.6 g).
Got This light brown oil was distilled under reduced pressure to obtain 31.2 g of the objective ethyl 5-methyl-7,8-dihydro-6-chromanate. (B.p.120-140 / 2mmHg
Yield 55.3%)

Example 5 Preparation of 5-methyl-7,8-dihydro-6-chromanic acid isopropyl ester: 40 g of 4-oxo-2-methyl-2-cyclohexenecarboxylic acid isopropyl ester (purity 94.8%,
193 mol), 1-bromo-3-chloropropane 7
5.6 g, NMP 144 g and potassium iodide 2.66
g was charged and heated to 140 ° C. under a nitrogen stream while stirring. Add 53.1 g of powdered potassium carbonate,
Stirred at 0 ° C. for 2 hours. The reaction mixture was cooled to 5 ° C or lower and then filtered. The residue was washed with ethyl acetate, and the obtained filtrate was washed with saturated brine / water (1: 1). The ethyl acetate solution was dried over magnesium sulfate and then concentrated to obtain 67.5 g of a light brown oil. The light brown oil was distilled under reduced pressure to obtain 25.1 g of the target isopropyl 5-methyl-7,8-dihydro-6-chromanate.
(B.p. 130-135 / 1.5 mmHg yield 55%)

Example 6 Preparation of 5-methyl-7,8-dihydro-6-chromanic acid ethyl ester: 5-methyl-7,8-dihydro-6-chroman was prepared in the same manner as in Example 4 except that potassium iodide was not added. 22.4 g of ethyl acidate was obtained (yield 39.6%).

Example 7 Preparation of 4-oxo-2-methyl-2-cyclohexenecarboxylic acid isopropyl ester: 144.2 g (1 mo) of acetoacetic acid isopropyl ester
l) and 7 ml of piperidine in a nitrogen atmosphere,
Paraformaldehyde 15 g (0.5
mol) was added to a small amount. After stirring at 90 to 95 ° C. for 31 hours and then distilling under reduced pressure, isopropyl 4-oxo-2-methyl-2-cyclohexenecarboxylate 62.
9 g (purity 93%) were obtained. Oil, B.I. p. 122-130 ℃
/ 6 mmHg. Yield 59.6%.

Reference Example Preparation of ethyl 5-methyl-7,8-dihydro-6-chromancarboxylate 18.2 g (0.10 mol) of ethyl 4-oxo-2-methyl-2-cyclohexenecarboxylate was added to KOBu t.
-Butanol solution (K: 12.0 g and t-butanol 2
Then, 26.8 g (0.133 mol) of 1,3-dibromopropane was added dropwise. After heating under reflux for 4 hours, concentrate under reduced pressure, and dilute hydrochloric acid (1.1 eq) under cooling.
Was added and extracted with 200 ml of ether. The organic layer was dried (magnesium sulfate), concentrated, and then distilled under reduced pressure. B.
p. 120-140 ° C / 2mmHg: 18g However, this is a mixture of the compound and other by-products which are considered to be spiro compounds by gas chromatography and thin layer chromatography, and the object can be obtained in high purity. I couldn't.

[0029]

INDUSTRIAL APPLICABILITY According to the present invention, 5-methyl-7,8-dihydro-6-chroman which is a useful intermediate in the process for producing 1-alkyl 1,2-dibenzoylhydrazines known to have insecticidal activity The acid ester can be industrially manufactured at low cost and in good yield.

Claims (15)

[Claims] 1. The following formula (1): (In the formula, R represents a C _{1 to} C ₆ lower alkyl group excluding an ethyl group.) 5-methyl-7,8-dihydro-6-chromanate ester 2. The compound according to claim 1, wherein R is a methyl group, an isopropyl group, an n-propyl group, an n-butyl group or a t-butyl group. 3. The following formula (2): (In the formula, R represents a C ₁ -C ₆ lower alkyl group.)
4-oxo-2-methyl-2-cyclohexenecarboxylic acid ester represented by the following formula (3) (Wherein X and Y represent a halogen atom) in the presence of a base in the two-phase system of water and a water-insoluble solvent, the following formula (1) 4] (In the formula, R represents a C ₁ -C ₆ lower alkyl group.) A method for producing 5-methyl-7,8-dihydro-6chromanate ester 4. The compound represented by the formula (2) and the compound represented by the formula (3) are reacted in the presence of a base in a polar aprotic solvent, wherein A method for producing 5-methyl-7,8-dihydro-6-chromanate represented by 1). 5. The method according to claim 2, wherein X is a bromine atom and Y is a chlorine atom. 6. The method according to claim 2, which is carried out by adding a phase transfer catalyst such as a quaternary ammonium salt or a phosphonium salt. 7. The method according to claim 3, 5 or 6, wherein the base used is sodium hydroxide or potassium hydroxide. 8. The water-insoluble solvent used is dichloromethane,
The method according to any one of claims 3, 5, 6 and 7, which is chlorobenzene, dichlorobenzene, toluene or xylene. 9. The method according to claim 4, wherein the base used is potassium carbonate, sodium carbonate or calcium carbonate. 10. The polar aprotic solvent used is N-methylpyrrolidinone, N, N-dimethylformamide,
The method according to claim 4, which is N, N-dimethylacetamide or N, N-dimethylimidazolidinone. 11. The method according to claim 4, wherein the reaction is carried out in the presence of potassium iodide. 12. The method according to any one of claims 4, 5, 9, 10 and 11, wherein the reaction temperature range is 90 to 150 ° C. 13. The method according to claim 3, wherein R is a methyl group, an ethyl group, an isopropyl group, an n-propyl group, an n-butyl group or a t-butyl group. 14. The following formula (2): (In the formula, R is C excluding methyl, ethyl and t-butyl groups.
_It represents a lower alkyl group of _{1 to} C ₆ . ) 4-oxo-2-methyl-2-cyclohexenecarboxylic acid ester represented by 15. R is an isopropyl group, n-propyl, n
The compound according to claim 14, which is a -butyl group.