JPH07133245A - Production of chroman carboxylic acid and intermediate thereof and production thereof - Google Patents

Abstract

PURPOSE:To obtain a novel compound which is used in the production of a synthetic intermediate for chroman carboxylic acid derivative which is useful as a synthetic intermediate for medicines and agrochemicals. CONSTITUTION:A compound of formula I (R<1>, R<2> are H, alkyl; R<3>, R<4> are H, methyl; R<5> is halogen, hydroxyl, alkyloxy, alkylsulfonyloxy; X1 is halogen), for example, 1-(3-chloropropyloxy)-2,4-dibromo-6-t-butyl-3-methylbenzene. The compound of formula I is obtained by halogenation of a compound of formula II, and the reaction of the product of formula III with a halide of formula IV in the presence of a base in the presence or absence of a phasetransfer catalyst in a solvent. Further, the compound of formula I is allowed to react with metallic magnesium in the presence or absence of a catalyst in a solvent and further react with carbon dioxide or a compound of formula V (R<1> is H, alkyl, phenyl; halogen) or of formula VI (R<8> is alkyl) to give a chroman carboxylic acid derivative of formula VII (R<11> is H, OH).

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a process for producing a chromancarboxylic acid derivative useful as a synthetic intermediate for pharmaceuticals and agricultural chemicals, an intermediate thereof and a process for producing the same.

[0002]

2. Description of the Related Art Heretofore, several methods for producing chromancarboxylic acid derivatives have been known.
Construction of chroman ring (J. Org. Chem. 37 P8
41 (1973), Helv. Chem. Acta. 5
6 P2981 (1973)), and then introducing a carbonyl group by Friedel-Crafts reaction or the like. Moreover, a synthetic method of a chromancarboxylic acid derivative using a Grignard reaction using metallic magnesium is not known. In general, a large number of alkylphenyl ethers are known, and some methods of synthesizing a chroman derivative by the ring-closing reaction of the alkylphenyl ethers are also known (for example, J.O.
rg. Chem. 37 P841 (1973), Hel
v. Chem. Acta. 56 P2981 (197
3)). The alkyl phenyl ether derivative of the present invention and its intermediate, 2,4-dibromo-6-t-butyl-3
-Methylphenol is a synthetic intermediate of a chroman derivative and is a novel compound.

[0003]

There is a demand for a method for inexpensively producing a chroman derivative useful as a synthetic intermediate for pharmaceuticals and agricultural chemicals in a short number of steps.

[0004]

The inventors of the present invention have achieved the present invention as a result of earnest studies to solve the above-mentioned problems. That is, the present invention has the general formula (1)

[0005]

[Chemical 11]

(R ¹ and R ² each independently represent a hydrogen atom or an alkyl group, R ³ and R ⁴ each independently represent a hydrogen atom or a methyl group, and R ⁵ represents a halogen atom, a hydroxyl group or an alkyl group. An oxy group and an alkanesulfonyloxy group, and X ¹ represents a halogen atom.)
And a method for producing the same. The compound of general formula (1) can be produced as follows. That is, the general formula (2)

[0007]

[Chemical 12]

(Wherein R ¹ and R ² each independently represent a hydrogen atom), which is obtained by halogenating a compound represented by the general formula (3)

[0009]

[Chemical 13]

(Wherein R ¹ and R ² are as defined above, X ¹ is a halogen atom), and a compound represented by the general formula (4)

[0011]

[Chemical 14]

(In the formula, R ³ and R ⁴ each independently represent a hydrogen atom or a methyl group, R ⁵ is a halogen atom,
It represents a hydroxyl group, an alkyloxy group or an alkanesulfonyloxy group, and X ² represents a halogen atom. ) It can manufacture by making it react with the halide represented.

In the above reaction, examples of the solvent for halogenating the compound of the general formula (2) by a known method include carbon tetrachloride, chlorinated solvents such as chloroform, carbon disulfide, acetic acid and the like. Acetic acid is preferred. Examples of the halogenating agent include bromine, chlorine, N-bromosuccinimide, and N-chlorosuccinimide, with bromine or chlorine being preferred, and bromine being more preferred. The amount used is preferably 2 to 3 equivalent moles relative to the compound of the general formula (2). Reaction temperature is 0
C to room temperature is preferred.

The solvent used in the reaction of the compound of the general formula (3) thus obtained with the compound of the general formula (4) is usually a water-soluble aprotic polar solvent, preferably dimethylformamide and N-methylpyrrolidinone. , Dimethylimidazolidinone, and more preferably dimethylformamide and N-methylpyrrolidinone. The base used when the solvent is dimethylformamide is preferably sodium hydride, and the amount to be added is preferably 1.0 to 1.2 equivalents relative to the compound of the general formula (3). When N-methylpyrrolidinone is used, the base is preferably potassium carbonate, and the addition amount is 1.0 to 10 parts with respect to the compound of the general formula (3).
2.0 equivalents are preferred. More preferably 1.0-1.
It is 2 equivalents. At this time, if a small amount of the phase transfer catalyst is present in the reaction system, the reaction proceeds rapidly. Tetrabutylammonium bromide is preferable as the phase transfer catalyst, and it is preferable to add 1 to 10 mol% to the compound of the general formula (3). The reaction temperature is preferably in the range of 0 ° C to 50 ° C.

Examples of R ^{1 to} R ⁵ and X ¹ in the compound of the general formula (1) obtained by the present invention include those mentioned above. Preferably, R ¹ and R ² are each independently a hydrogen atom or a lower atom. Alkyl group, C ₃ to C ₆ branched alkyl group, R ³ and R ⁴ are each independently a hydrogen atom or a methyl group, R ⁵ is a chlorine atom, a bromine atom, a methyloxy group, a methanesulfonyloxy group, p-toluenesulfonyl group An oxy group, a trifluoromethanesulfonyloxy group, X ¹ is a chlorine atom or a bromine atom, more preferably R ¹ is a methyl group, R ² is a t-butyl group, R ³ and R ⁴ are hydrogen atoms, and R ⁵ is chlorine. Atom, bromine atom, hydroxyl group, methoxy group, methanesulfonyloxy group,
It is a p-toluenesulfonyloxy group and a trifluoromethanesulfonyloxy group, and X ¹ is a chlorine atom or a bromine atom. In addition, R ¹ and R in the compound of the general formula (2) are
^Examples of ² include those described above. Preferably, R ¹ and R ² are each independently a hydrogen atom, a lower alkyl group, a C ₃ -C ₆ branched alkyl group, and more preferably R ¹ is a methyl group. R ² is a t-butyl group. Further, R ¹ , R ² and X ¹ in the compound of the general formula (3) are
Examples of the above include, but preferably R ¹ ,
R ² is independently a hydrogen atom, a lower alkyl group, C
_{It is a 3-} C ₆ branched alkyl group, X ¹ is a chlorine atom or a bromine atom, and more preferably R ¹ is a methyl group or R ^1.
2 is a t-butyl group and X ¹ is a bromine atom. Then, R ³ , R ⁴ , R ⁵ and X ² in the compound of the general formula (4) are
Examples of the above include, but preferably R ³
And R ⁴ are each independently a hydrogen atom or a methyl group, R ⁵ is a chlorine atom, a bromine atom, a methoxy group, a methanesulfonyloxy group, a p-toluenesulfonyloxy group,
A trifluoromethanesulfonyloxy group, X ² is a chlorine atom or a bromine atom, more preferably R ³ and R ⁴ are hydrogen atoms, R ⁵ is a chlorine atom, and X ² is a bromine atom.

The compound of the general formula (1) thus obtained is reacted with magnesium metal in a solvent in the presence or absence of a catalyst, and then carbon dioxide or the general formula (5).

[0017]

[Chemical 15]

(In the formula, R ⁶ represents a hydrogen atom, an alkyl group, an optionally substituted phenyl group, an alkyloxy group or an optionally substituted phenoxy group, and R ⁷ is a halogen atom,
NR ¹² R ¹³ and —OR ¹⁴ are shown, R ¹² and R ¹³ are lower alkyl groups, and R ¹⁴ is an alkyl group or an optionally substituted phenyl group. ) Or a compound represented by the general formula (6)

[0019]

Embedded image R ⁸ —CN (6)

(Wherein R ⁸ represents an alkyl group or an optionally substituted phenyl group) or a compound represented by the general formula (7)

[0021]

Embedded image R ⁹ —C (OR ¹⁰ ) ₃ (7)

(R ⁹ represents a hydrogen atom, an alkyl group or an optionally substituted phenyl group, and R ¹⁰ represents a lower alkyl group.) General formula (8)

[0023]

[Chemical 18]

(Wherein R ^{1 to} R ⁴ have the same meanings as described above, R ¹¹ represents a hydrogen atom, a hydroxyl group, or R ⁶ , R ⁸ and R ⁹ defined above). An acid derivative can be produced.

In the above reaction, examples of the solvent include ether type solvents such as diethyl ether, tetrahydrofuran, diisopropyl ether, and methyl-t-butyl ether. Among them, diethyl ether and tetrahydrofuran are preferable, and tetrahydrofuran is more preferable. . At a reaction temperature of room temperature, metallic magnesium is reacted with a small amount of the compound of the general formula (1), and when self-reflux starts due to the heat of reaction, the remaining compound of the general formula (1) is added so that the reflux continues. Is good. And 0-
It is preferable to reflux for about 2 hours. The metal magnesium used in the reaction is finely ground metal, preferably a commercially available Grignard reagent, which is used in an amount of 2.0 to 4 with respect to the compound of the general formula (1). It is 0.0 equivalent and preferably 2.0 to 3.0 equivalent. At this time, iodine, 1,2-dibromoethane, which is used as a catalyst when preparing a general Grignard reagent,
The reaction proceeds rapidly by adding a catalytic amount of bromoethane.

After confirming the disappearance of the compound of the general formula (1) by various kinds of chromatography, a chromancarboxylic acid derivative is obtained by adding a carbonyl compound of the general formula 5. The form of carbon dioxide used at this time is dry ice or liquefied carbon dioxide gas. In the case of dry ice, the reaction liquid is cooled to room temperature or lower, and then a crushed product is added in a large excess. It is also possible to pour the reaction solution on a large excess of dry ice.
When liquefied carbon dioxide is used, the gas is dried with a desiccant such as silica gel or concentrated sulfuric acid -30 ° C
It is advisable to blow between the boiling points of the solvent used, preferably a large excess of the boiling point of the solvent used.

When the compounds (5) to (7) specified above are reacted, the reaction solution is cooled to -78 ° C to 0 ° C,
It is preferable that 1.0 to 3.0 equivalents of the compound of the general formula (1) are added dropwise thereto. It was also found that the reaction proceeds rapidly by adding a catalytic amount of cupric iodide when introducing the carbonyl group as described above.

Examples of R ⁶ and R ⁷ in the compound of the general formula (5) used as a raw material in the present invention include those mentioned above. Preferably, R ⁶ is a hydrogen atom, a methyl group, a phenyl group, a methoxy group, A phenoxy group, R ⁷ is a chlorine atom, a bromine atom, —NR ¹² R ¹³ , —OR ¹⁴ ;
R ¹² and R ¹³ are methyl groups, R ¹⁴ is a lower alkyl group,
It is a phenyl group, and more preferably, R ⁷ is —NR ¹² R ¹³ when R ⁶ is a hydrogen atom, and R ¹² and R ¹³ are methyl groups at this time. When R ⁶ is a methoxy group, R ⁷ is a chlorine atom. In addition, R in the compound of the general formula (6)
^Examples of ⁸ include those mentioned above, but R ⁸ is preferable.
Is a lower alkyl group or a phenyl group, and more preferably R ⁸ is a methyl group or a phenyl group. Further, in the general formula (7), R ⁹ and R ^{10 are} as described above, but preferably R ⁹ represents a hydrogen atom, a methyl group, a phenyl group, and R ¹⁰ represents a methyl group or an ethyl group. More preferably, R ⁹ represents a hydrogen atom and R ¹⁰ represents an ethyl group. And, as the R ^{1 to} R ⁴ and R ¹¹ in the compound of the general formula (8) which can be produced by the present invention, those mentioned above can be mentioned, but preferably R ¹ and R ² are each independently a hydrogen atom or a lower alkyl. A group, a C _{3 to} C ₆ branched alkyl group,
R ³ and R ⁴ are each independently a hydrogen atom or a methyl group, more preferably R ¹ is a methyl group, R ² is a t-butyl group, R ³ and R ⁴ are hydrogen atoms, R ¹¹ is a hydrogen atom, A methyl group, a phenyl group, a methoxy group, and a hydroxyl group.

The compounds of the general formula (8), if R ² is a hydrogen atom as it otherwise substituents known in JP-converted EP43492 a hydrogen atom desorb the R ^2, Lepidoptera It can be used as a raw material for a benzoylhydrazine insecticide having an excellent insecticidal effect against harmful insects.

[0030]

EXAMPLES The present invention will be described more concretely with reference to the following examples.

Example 1 Preparation of 2,4-dibromo-6-t-butyl-3-methylphenol: t-butyl-m-
Cresol (50 g, 304 mmol) in acetic acid 400 m
bromine (124 g, 77
6 mmol) is added dropwise and the mixture is stirred at room temperature for 3 hours.
Aqueous sodium hydrogen sulfite solution was added, extracted with ethyl acetate, washed with water, and the solvent was evaporated under reduced pressure to give 2,4-dibromo-6.
-T-butyl-3-methylphenol (oil, 96g)
Was obtained with a yield of 98%. ( ¹ H-NMR 1.37 ppm
(S, 9H), 2.52ppm (s, 3H), 5.90
ppm (s, 1H), 7,39 ppm (s, 1H))

Example 2 Preparation of 1- (3-chloropropyloxy) -2,4-dibromo-6-t-butyl-3-methylbenzene: 2,4-dibromo-6-t-butyl-
3-Methylphenol (50 g, 155 mmol) is dissolved in 500 ml of dimethylformamide, sodium hydride (60% in Oil 7.5 g, 186 mmol) is added, and the mixture is stirred. 3-Bromo-1-chloropropane (25.6 g, 163 mmol) was added thereto, and the mixture was stirred at 30 to 40 ° C. for 6 hours. After adding water and extracting with toluene, the solvent was distilled off under reduced pressure and 1- (3-chloropropyloxy) -2,4.
-Dibromo-6-t-butyl-3-methylbenzene (oil, 58g) was obtained with a yield of 94%. ( ¹ H-NMR
1.37 ppm (s, 9H), 2.35 ppm (tt,
J = 6.27, 5.94Hz, 2H), 2.55ppm
(S, 3H), 3.82 ppm (t, J = 6.27H
z, 2H), 4.13 ppm (t, J = 5.94 Hz,
2H), 7.47ppm (s, 1H))

Example 3 Preparation of 1- (3-chloropropyloxy) -2,4-dibromo-6-t-butyl-3-methylbenzene: 2,4-dibromo-6-t-butyl-
3-Methylphenol (20 g, 62 mmol) was added to N-
It is dissolved in 50 ml of methylpyrrolidinone, potassium carbonate (9.4 g, 68 mmol) is added, the temperature is raised to about 70 ° C. and the mixture is stirred for 30 minutes. The temperature was lowered to 40 ° C., 0.2 g of tetrabutylammonium bromide and 3-bromo-1-chloropropane (10 g, 63 mmol) were added, and the mixture was stirred at room temperature for 4 hours.
Stir for hours. Water was added, the mixture was extracted with toluene, the solvent was evaporated under reduced pressure, and 1- (3-chloropropyloxy) -2,4-dibromo-6-t-butyl-3-methylbenzene (oil, 2
4.2 g) was obtained with a yield of 98%.

Example 4 Preparation of 1- (3-hydroxypropyloxy) -2,4-dibromo-6-t-butyl-3-methylbenzene: 2,4-dibromo-6-t-butyl-3-methyl Phenol (5 g, 15 mmol) is dissolved in 20 ml of dimethylformamide, sodium hydride (60% inOil 0.75 g, 18.6 mmol) is added, and the mixture is stirred. 3-Bromopropanol (2.1
5 g, 15 mmol) and stirred at 100 ° C. for 6 hours. After adding water, the mixture was extracted with ethyl acetate and the solvent was distilled off under reduced pressure.
Purified by column chromatography, 1- (3-
Chloropropyloxy) -2,4-dibromo-6-t-
Butyl-3-methylbenzene (oil, 3.3 g) was obtained with a yield of 58%. ( ¹ H-NMR 1.37 ppm (s,
9H), 2.08 ppm (tt, J = 5.94, 5.9)
3Hz, 2H), 2.55ppm (s, 3H), 3.9
6ppm (t, J = 5.94Hz, 2H), 4.16p
pm (t, J = 5.93Hz, 2H), 7.48ppm
(S, 1H))

Example 5 Preparation of 1- (3-chloropropyloxy) -2,4-dibromo-3-methylbenzene:
2,4-dibromo-3-methylphenol (4 g, 15
(mmol) was dissolved in 15 ml of N-methylpyrrolidinone, potassium carbonate (2.28 g, 16.5 mmol) was added, the temperature was raised to about 60 ° C, and the mixture was stirred for 1 hour. The temperature was lowered to 40 ° C, and 3-bromo-1-chloropropane (2.36
g, 15 mmol) and stirred at room temperature for 4 hours. Water was added and the mixture was extracted with toluene and the solvent was distilled off under reduced pressure to obtain 1- (3-chloropropyloxy) -2,4-dibromo-3methylbenzene (oil, 4.5 g) with a yield of 87%. ( ¹ H
-NMR 2.14-2.40 ppm (m, 2H),
2.58 ppm (s, 3H), 3.81 ppm (t, J
= 6.26 Hz, 2H), 4.14 ppm (t, J =
5.94 Hz, 2H), 6.63 ppm (d, J = 8.
57 Hz, 1 H), 7.43 ppm (d, J = 8.57)
Hz, 1H))

Example 6 Preparation of 8-t-butyl-5-methylchroman-6-carboxylic acid: metallic magnesium (
0.64 g, 26.4 mmol) of THF (10 ml)
A catalytic amount of iodine is added to the suspension solution and stirred. There 1-
(3-chloropropyloxy) -2,4-dibromo-6
-T-butyl-3-methylbenzene (5 g, 12.6 m
(mol) and the mixture is heated under reflux for 2 hours. The reaction solution was cooled to 10 ° C. and crushed into finely divided dry ice (100
g) was added to the reaction solution and the mixture was allowed to stand to room temperature. Water was added, the mixture was extracted with toluene, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. Purification was performed by silica gel chromatography to obtain the target 8-t-butyl-5-methylchroman-6-carboxylic acid (white solid, 2.0 g) in a yield of 63%.
Got with.

Example 7 Preparation of 5-methylchroman-6-carboxylic acid: Magnesium metal (0.64 g, 26.
A catalytic amount of iodine is added to a suspension solution of 4 mmol) in THF (10 ml), and the mixture is stirred. 1- (3-chloropropyloxy) -2,4-dibromo-3-methylbenzene (5
g, 12.6 mmol) and the mixture is heated under reflux for 2 hours. The reaction solution was cooled to 10 ° C., finely crushed dry ice (100 g) was added to the reaction solution, and the mixture was allowed to stand to room temperature. Water was added, the mixture was extracted with toluene, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. Purification was performed by silica gel chromatography to obtain the desired 5-methylchroman-6-carboxylic acid (white solid, 1.5 g) in a yield of 60%.
Got with.

Example 8 Preparation of 5-methylchroman-6-carboxylic acid: Magnesium metal (0.64 g, 26.
A catalytic amount of dibromoethane and cupric iodide are added to a suspension solution of 4 mmol) in THF (10 ml), and the mixture is stirred. 1- (3-Chloropropyloxy) -2,4-dibromo-3-methylbenzene (5 g, 12.6 mmol) was added dropwise thereto, and the mixture was heated under reflux for 2 hours. Under reflux, a large excess amount of carbon dioxide gas dried with silica gel and sulfuric acid was blown into the reaction solution. The reaction mixture was cooled to room temperature, water was added, the mixture was extracted with toluene, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. Purification was performed by silica gel chromatography to obtain the desired 5-methylchroman-6-carboxylic acid (white solid, 1.5 g) with a yield of 60%.

Example 9 Preparation of 8-t-butyl-5-methylchroman-6-aldehyde: Magnesium metal (
0.64 g, 26.4 mmol) of THF (10 ml)
A catalytic amount of iodine is added to the suspension solution and stirred. There 1-
(3-chloropropyloxy) -2,4-dibromo-6
-T-butyl-3-methylbenzene (5 g, 12.6 m
(mol) and the mixture is heated under reflux for 2 hours. The reaction solution was cooled to −20 ° C. and N, N-dimethylformamide (1.38 g, 18.9 mmol) was added. The mixture was allowed to stand to room temperature, water was added, the mixture was extracted with ethyl acetate, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. Purification was performed by silica gel chromatography to obtain the desired 8-t-butyl-5-methylchroman-6-aldehyde (oil, 1.
3 g) was obtained with a yield of 46%.

Example 10 Preparation of methyl 8-t-butyl-5-methylchroman-6-carboxylate: Metallic magnesium (0.64 g, 26.4 mmol) in THF (10
ml) A catalytic amount of iodine is added to the suspension solution and stirred. There (3-chloropropyloxy) -2,4-dibromo-6
-T-butyl-3-methylbenzene (5 g, 12.6 m
(mol) and the mixture is heated under reflux for 2 hours. The reaction solution was cooled to -78 ° C, and methyl chlorocarbonate was added. After returning to room temperature with stirring, adding water and extracting with ethyl acetate,
After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. Purification was performed by silica gel chromatography to obtain the desired methyl 8-t-butyl-5-methylchroman-6-carboxylate (oil, 1.3 g).

[0041]

INDUSTRIAL APPLICABILITY According to the present invention, an intermediate for producing a chromancarboxylic acid derivative useful as an intermediate for pharmaceuticals and agricultural chemicals can be obtained, and by using the intermediate, the construction of a chroman ring and the introduction of a carbonyl group are simultaneously carried out. , Chroman carboxylic acid derivative can be easily synthesized.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location C07C 303/30 309/65 7419-4H C07D 311/58 // C07B 61/00 300

Claims (17)

[Claims] 1. A general formula (1): (R ¹ and R ² each independently represent a hydrogen atom or an alkyl group, R ³ and R ⁴ each independently represent a hydrogen atom or a methyl group, and R ⁵ is a halogen atom, a hydroxyl group, an alkyloxy group, A compound represented by an alkanesulfonyloxy group and X ¹ represents a halogen atom.). 2. R ¹ is a methyl group, R ² is a t-butyl group, R
³ , R ⁴ are hydrogen atoms, R ⁵ is chlorine atom, bromine atom, hydroxyl group, methoxy group, methanesulfonyloxy group, p-toluenesulfonyloxy group, trifluoromethanesulfonyloxy group, X ¹ is chlorine atom, bromine atom The compound of claim 1, which is 3. A general formula (2): (Wherein R ¹ and R ² are as defined above) and are halogenated to give a compound represented by the general formula (3): (Wherein R ¹ , R ² and X ¹ are as defined above) in a solvent, in the presence of a base, in the presence or absence of a phase transfer catalyst, the compound represented by the general formula (4): Chemical 4] (X ² is a halogen ^{atom, R 3, R 4, R} 5 are. Showing the same as above defined) preparation of compounds of general formula (1), characterized in that is reacted with halide represented by. 4. The method according to claim 3, wherein the solvent is a water-soluble aprotic polar solvent. 5. The method according to claim 3, wherein the base is an alkali metal carbonate or an alkali metal hydride. 6. The method according to any one of claims 3 to 5, wherein the aprotic polar solvent is N-methylpyrrolidinone, dimethylimidazolinone or dimethylformamide. 7. The method according to claim 3, wherein the base is potassium carbonate or sodium hydride. 8. The method according to claim 3, wherein the phase transfer catalyst is tetrabutylammonium bromide. 9. A compound represented by the general formula (1): (Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and X ¹ are as defined above) are reacted with metallic magnesium in a solvent in the presence or absence of a catalyst. Then, carbon dioxide or the general formula (5) (In the formula, R ⁶ represents a hydrogen atom, an alkyl group, an optionally substituted phenyl group, an alkyloxy group or an optionally substituted phenoxy group, R ⁷ is a halogen atom, —NR ¹² R ¹³ ,
Represents -OR ¹⁴ , R ¹² and R ¹³ represent a lower alkyl group,
R ¹⁴ represents an alkyl group or an optionally substituted phenyl group. Or a compound represented by the general formula (6): embedded image R ⁸ —CN (6) (wherein R ⁸ represents an alkyl group or an optionally substituted phenyl group) (7) embedded image R ⁹ —C (OR ¹⁰ ) ₃ (7) (In the formula, R ⁹ represents a hydrogen atom, an alkyl group or an optionally substituted phenyl group, and R ¹⁰ represents a lower alkyl group. ), Which is obtained by reacting any of the compounds represented by the formula (8). (Wherein R ^{1 to} R ⁴ have the same meanings as described above, R ¹¹ represents a hydrogen atom, a hydroxyl group, or R ⁶ defined above,
Shows the R ^8, R ^9. ) A method for producing a chromancarboxylic acid derivative represented by: 10. The method according to claim 9, wherein the solvent is diethyl ether or tetrahydrofuran. 11. The method according to claim 9, wherein one of iodine, 1,2-dibromoethane and bromoethane is added as a catalyst during the reaction with magnesium metal. 12. The cupric iodide as a catalyst is added in the reaction of introducing a carbonyl group.
The method according to any one of 1 to 11. 13. A compound of the general formula (1) is prepared by halogenating the compound of the general formula (2) to produce a compound of the general formula (3) and then reacting it with a halide of the general formula (4). A compound is prepared and then reacted with magnesium metal in a solvent in the presence or absence of a catalyst, followed by carbon dioxide or any of the compounds of the above general formulas (5) (6) or (7). A method for producing the compound represented by the general formula (8), characterized in that 14. R ⁷ is a methyl group, R ² is a hydrogen atom or a t-butyl group, R ³ and R ⁴ are hydrogen atoms, R ⁵ is a chlorine atom, and when R ⁶ is a hydrogen atom, R ⁷ is -NR ¹² R
^When R ¹³ and R ⁶ are methoxy groups, R ⁷ is a chlorine atom, and R ^{8 is}
Is a methyl group or a phenyl group, R ⁹ is a hydrogen atom, R ¹⁰ is an ethyl group, R ¹¹ is a hydrogen atom, a methyl group, a phenyl group, a hydroxyl group, a methoxy group, X ¹ is a bromine atom, R ¹² and R.
The method according to any one of claims 3 to 13, wherein ¹³ is a methyl group. 15. The following formula: 2,4-dibromo-6-t-butyl-3-methylphenol represented by 16. t-Butyl-m-cresol in a solvent,
2,4-dibromo-6-t characterized by bromination
-Method for producing butyl-3-methylphenol. 17. The method according to claim 16, wherein the solvent is acetic acid and the brominating agent is bromine.