JPH07109269A - Production of chromane derivative and intermediate thereof - Google Patents

Abstract

PURPOSE:To industrially and advantageously obtain the compound useful as an intermediate for benzoylhydrazine insecticides, etc., by esterifying a specific omicron-allylphenol compound, reacting the reaction product with a hydrogen halide in the presence of an active radical, and further treating the product with a base. CONSTITUTION:A method for producing a chromane derivative comprises reacting a compound of formula I (R<1> is 1-2C alkyl, halogen; R<2> 18 4-6C t-alkyl; R<3>, R<4> are H, methyl) (e.g. 2-allyl-3-hydroxy-4-t-butyl-toluene) with a compound of formula: R<5> COY [R<5> is 1-4C alkyl, 1-4C alkoxy; Y is halogen, formula: OCOR<5>, formula: OSO2R<6> (R<6> is alkyl, haloalkyl, aryl)] (e.g. acetic acid anhydride) in the presence or absence of a base in a solvent or in a solvent-free state, reacting the produced compound of formula II with a hydrogen halide in the presence of an azo compound, a peroxide, oxygen, etc., or under the irradiation of light in a solvent, and subsequently treating the produced compound of formula III (X is halogen) with a base in a solvent, thus obtaining the objective compound of formula IV.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a process for producing a chroman derivative and an intermediate thereof. The chroman derivative is useful as an intermediate for medicines and agricultural chemicals.

[0002]

2. Description of the Related Art A method of producing a chroman derivative by a thermal rearrangement reaction of a propargyl ether derivative is known. However, since propargyl halides used in the production process are expensive and dangerous, a new production method that can be produced inexpensively and safely has been desired.

[0003]

DISCLOSURE OF THE INVENTION The present inventors have conducted research for the purpose of obtaining a chroman derivative industrially advantageously, and as a result found a novel production method thereof and completed the present invention. That is, the present invention has the general formula (4)

[0004]

[Chemical 13]

The present invention relates to a process for producing a chroman derivative represented by the formula (wherein R ¹ , R ² , R ³ and R ⁴ are as described above) and an intermediate thereof.

The novel manufacturing method of the present invention is as follows.

[0007]

[Chemical 14]

1) First step General formula (2)

[0009]

[Chemical 15]

(Wherein R ¹ is a C ₁ -C ₂ alkyl group or a halogen atom, R ² is a C ₄ -C ₆ tertiary alkyl group, and R ³ and R ⁴ are independently hydrogen. An atom or a methyl group, and R ⁵ represents a C ₁ -C ₄ alkyl group or a C ₁ -C ₄ alkoxy group.) Can be produced as follows. That is, the general formula (1)

[0011]

[Chemical 16]

(Wherein R ¹ , R ² , R ³ and R ⁴ are the same as defined above) in the presence or absence of a base in a solvent or without solvent in the formula R ⁵ COY
(In the formula, R ⁵ represents the above, Y represents a halogen atom,
It can be produced by reacting with a compound of OCOR ⁵ or OSO ₂ R ⁶ (R ⁶ represents an alkyl group, a haloalkyl group or an aryl group).

As the solvent used in the above reaction, ether hydrocarbons such as tetrahydrofuran, MeOH, E
Aliphatic lower alcohols such as tOH, aliphatic lower hydrocarbons such as hexane, aromatic hydrocarbons such as toluene, lower fatty acids and their anhydrides, dimethylformamide, dimethylsulfoxide, water and mixed solvents thereof, etc. However, ether hydrocarbons, aromatic hydrocarbons, lower fatty acids and their anhydrides are preferable. It can also be carried out without solvent.

As the base used in the above reaction, KOH,
Metal hydroxide such as NaOH, K ₂ CO ₃ , Na ₂ CO
Metal carbonates such as ₃ , MeONa, EtONa, t-B
Alkali metal salts of aliphatic lower alcohols such as uOK,
Metal hydrides such as NaH, organic bases such as pyridine and triethylamine, and particularly organic bases can also be used as a solvent. It can also be carried out in the absence of a base.

When a base is used, the amount used is usually 0.5 to 5 equivalents, preferably 1 to 2 equivalents.

The compound of the general formula R ⁵ COY (in the formula, R ⁵ and Y are the same as defined above) used in the above reaction, is a lower fatty acid chloride such as acetyl chloride,
Lower fatty acid anhydrides such as acetic anhydride, lower fatty acid mixed anhydrides such as AcOTf and alkyl chlorocarbonates such as methyl chlorocarbonate, especially lower fatty acid chlorides, lower fatty acid anhydrides and alkyl chlorocarbonates.

The amount of the compound of the general formula R ⁵ COY to be used is usually 1 equivalent to 10 equivalents, preferably 1 equivalent to 2 equivalents.

The reaction temperature is usually from -20 ° C to solvent reflux temperature,
The temperature is preferably −10 ° C. to solvent reflux temperature.

2) Second step General formula (3)

[0020]

[Chemical 17]

(Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵
Shows the same thing as the above, and X shows a halogen atom. )
The compound can be produced as follows. That is, the general formula (2)

[0022]

[Chemical 18]

(Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵
Indicates the same as above. It can be produced by reacting the compound represented by the formula (4) as a radical initiator in a solvent with a hydrogen halide under at least one condition selected from the presence of an azo compound, peroxide oxygen and under light irradiation.

Examples of the solvent used in the above reaction include aliphatic hydrocarbons such as hexane, aromatic hydrocarbons such as toluene and chlorobenzene, organochlorine hydrocarbons such as dichloromethane and aliphatic lower carboxylic acids, and mixed solvents thereof. And the like, preferably an aliphatic hydrocarbon,
Aromatic hydrocarbons and mixed solvents thereof.

The reaction temperature is usually 0 ° C. to solvent reflux temperature, preferably 20 ° C. to solvent reflux temperature.

Examples of the radical initiator used in the above reaction include azo compounds such as AIBN, peroxides such as benzoyl peroxide, oxygen and light.

The amount of radical initiator used is usually 0.001.
Equivalent to 1 equivalent, preferably 0.01 equivalent to 0.03.
It is 1 equivalent.

Examples of the hydrogen halide used in the above reaction include hydrogen bromide and hydrogen chloride, and hydrogen bromide is preferable.

The amount of hydrogen halide used is usually 1 equivalent to 5 equivalents, preferably 1 equivalent to 2 equivalents.

3) Third step General formula (4)

[0031]

[Chemical 19]

The compound of the formula (wherein R ¹ , R ² , R ³ and R ⁴ are the same as described above) can be produced as follows. That is, the general formula (3)

[0033]

[Chemical 20]

A compound represented by the formula (wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and X are the same as above) is produced by treating the compound with a base in a solvent. Can be done.

Examples of the solvent used in the above reaction include aromatic hydrocarbons such as toluene, organic chlorine hydrocarbons such as dichloromethane, aliphatic lower alcohols such as methanol and ethanol, ether hydrocarbons such as tetrahydrofuran, dimethylformamide, and the like. Examples thereof include dimethyl sulfoxide, water and a mixed solvent thereof, preferably aliphatic lower alcohol, ether hydrocarbon, dimethylformamide, dimethyl sulfoxide, water and a mixed solvent thereof.

The reaction temperature is usually -40 ° C to solvent reflux temperature, preferably -20 ° C to solvent reflux temperature.

Examples of the base include alkali metal hydroxides such as KOH and NaOH, alkali metal carbonates such as K2 CO3 and Na2 CO3, MeONa, EtONa and t-B.
Alkali metal salts of aliphatic lower alcohols such as uOK,
Alkali metal hydrides such as NaH, organic bases such as pyridine and triethylamine, preferably metal hydroxides, alkali metal carbonates, and alkali metal salts of aliphatic lower alcohols.

The amount used is usually 0.5 equivalent to 10
It is an equivalent, preferably 2 equivalents to 5 equivalents.

In the present invention, examples of the compound represented by the general formula (1) include 2-allyl-3-hydrox.
y-4-tert-butyltoluene, 3-aceto is an example of the compound represented by the general formula (2).
xy-2-allyl-4-tert-butyl-t
oluene and 2-allyl-3-methoxy
carbonyloxy-4-tert-butyl-
Toluene, as an example of the compound represented by the general formula (3), 3-acetoxy-2- (3-bromop
ropyl) -4-tert-butyl-tolue
ne and 2- (3-bromopropyl) -3-m
etoxycarbonyloxy-4-tert-
Butyltolue, 8-tert-butyl-5-met as an example of the compound represented by the general formula (4)
hyl-4-chromane and the like can be mentioned.

8-tert-Butyl-5-meth
yl-4-chromane then introduces, for example, a —COCH ₃ group at the 6-position, further converts this group into a carboxyl group, and eliminates the tert-butyl group at the 8-position by formula (5)

[0041]

[Chemical 21]

It is converted to a compound represented by: This compound is useful as an intermediate of a benzoylhydrazine compound having a high insecticidal activity against insect pests such as Lymoptera, Diptera, and Hemiptera known in JP-A-5-163266.

[0043]

EXAMPLES The method of the present invention will be specifically described below with reference to examples.

Example 1 3-Acetoxy-2-allyl-4-tert-
Production of butyl-toluene: 2-Allyl-
3-hydroxy-4-tert-butyl-to
luene 5 g, acetic anhydride 3.5 ml and pyri
Dine 2.2 ml mixture heated to reflux for 10 hours. Water was added to the reaction mixture, extraction was performed with AcOEt, and 10% H
It is washed with Cl water and saturated saline. After drying MgSO _{4, the} solvent was distilled off, and the obtained residue was subjected to silica gel column chromatography to obtain n-hexane-AcOEt.
From the flow fraction, 5 g (83%) of the desired compound is obtained as a colorless oil.

¹ H-NMR (CDCl ₃ , ppm)
δ: 1.32 (9H, s), 2.27 (3H, s),
2.32 (3H, s), 3.07 (2H, m), 4.8
0-5.00 (1H, m), 5.00-5.10 (1
H, m), 5.55-6.10 (1H, m), 6.98
(1H, d, J = 8.4 Hz), 7.19 (1H, d,
J = 8.4Hz)

Example 2 2-Allyl-3-methoxycarbonyl
Preparation of oxy-4-tert-butyltoluene: 2-Allyl-3-hydroxy-4-ter
5 g of t-butyl-toluene was added to anhydrous THF.
Dissolve in 50 ml and cool with NaH (60% in oi
l) Add 1.2 g. MeOCOCl at the same temperature
Add 2.3 ml and stir at room temperature for 3 hours. The reaction mixture was added to water, extracted with AcOEt, the organic layer was washed with water and saturated brine, dried over MgSO _{4, and the} solvent was distilled off. The obtained residue is subjected to silica gel column chromatography, and 5 g (78%) of the desired compound is obtained as a colorless oily substance from the n-hexane-AcOEt fraction.

¹ H-NMR (CDCl ₃ , ppm)
δ: 1.33 (9H, s), 2.28 (3H, s),
3.28 (H, dt, J = 1.5 and 5.9H
z), 3.87 (3H, s), 4.80-5.00 (1
H, m), 5.00-5.10 (1H, m), 5.55
-6.010 (1H, m), 7.00 (1H, d, J =
8.5Hz), 7.19 (1H, d, J = 8.5Hz)

Example 3 3-Acetoxy-2- (3-bromopropy)
l) Preparation of 4-tert-butyltoluene: 3-Acetoxy-2-allyl-4-ter
t-butyl-toluene 1g, 30% HBr
(Acetic acid solution) 1.2 ml and AIBN 66 mg were dissolved in chlorobenzene 5 ml and stirred at 70 ° C. for 1 hour,
The reaction solution is added to water and extracted with AcOEt. The organic layer was washed with saturated NaHCO ₃ water and saturated saline,
After drying SO _{4, the} solvent was distilled off. The obtained residue was subjected to silica gel column chromatography to obtain n-hexane-A.
Target bromide body 1.3 g (86
%) As a colorless oil.

¹ H-NMR (CDCl ₃ , ppm)
δ: 1.32 (9H, s), 1.90-2.20 (2
H, m), 2.31 (3H, s), 2.39 (3H,
s), 2.40-2.75 (2H, m), 3.46 (2
H, t, J = 5.9 Hz), 6.99 (1H, d, J =
8.4Hz), 7.19 (1H, d, J = 8.4Hz)

Example 4 2- (3-Bromopropyl) -3-metho
xy-carbonyloxy-4-tert-but
Production of yltolue: 2-Allyl-3-meth
oxycarbonyloxy-4-tert-but
2.9 g of yltoluene, 3.4 ml of 30% HBr (acetic acid solution) and 115 mg of AIBN are dissolved in 10 ml of chlorobenzene and stirred at 70 ° C. for 1 hour, and the reaction solution is added to water and extracted with AcOEt. The organic layer was washed with saturated aqueous NaHCO ₃ solution and saturated saline solution, and washed with MgSO 4.
₄ After drying, evaporate the solvent. The obtained residue was subjected to silica gel column chromatography, n-hexane-Ac
2.2 g (54
%) As a colorless oil.

¹ H-NMR (CDCl ₃ , ppm)
δ: 1.33 (9H, s), 1.85-2.15 (2
H, m), 2.31 (3H, s), 2.50-2.80
(2H, m) 3.44 (2H, t, J = 6.2H
z), 3.90 (3H, s), 6.99 (1H, d, J
= 8.4 Hz), 7.18 (1H, d, J = 8.4H)
z)

Example 5 8-tert-Butyl-5-methylcrom
Manufacture of ane: 3-Acetoxy-2- (3-bromprop
yl) -4-tert-butyltoluene 3
g was dissolved in 15 ml of dimethylsulfoxide and cooled under ice.
-Add 2 g of BuOK. After stirring for 1 hour at room temperature, the reaction mixture is poured into water and extracted with AcOEt, and the organic layer is washed with water and saturated saline. After drying over MgSO _{4, the} solvent was distilled off, and the resulting residue was subjected to silica gel column chromatography to obtain 2.3 g (91%) of the desired chroman derivative as a colorless oily substance from the n-hexane-AcOEt fraction. .

3-Acetoxy-2- (3-bro
mopropyl) -4-tert-butyltol
uene 4.2g dissolved in MeOH 50ml K
Add 1.8 g of OH and stir at room temperature for 15 hours. The reaction mixture is acidified with 10% aqueous HCl, extracted with AcOEt, and washed with saturated brine. The organic layer is Mg
After drying with SO _{4, the} solvent was distilled off, and the resulting residue was subjected to column chromatography to obtain n-hexane-AcOE.
From the t-stream, the target chroman derivative 1.5 g (5
7%) as a colorless oil.

¹ H-NMR (CDCl ₃ , ppm)
δ: 1.35 (9H, s), 1.82-2.20 (2
H, m), 2.16 (3H, s), 2.64 (2H,
t, J = 6.6 Hz), 4.13 (2H, t, J =
6.6 Hz), 6.66 (1H, d, J = 7.9H
z), 7.13 (1H, d, J = 7.9Hz)

[0055]

INDUSTRIAL APPLICABILITY According to the present invention, a chroman derivative useful as an intermediate for a benzoylhydrazine insecticide can be obtained in good yield.

Claims (8)

[Claims] 1. A compound represented by the general formula (1): (In the formula, R ¹ is a C ₁ -C ₂ alkyl group or a halogen atom, R ² is a C ₄ -C ₆ tertiary alkyl group, R ³
And R ⁴ each independently represent a hydrogen atom or a methyl group. ) In the presence or absence of a base in a solvent or in the absence of a solvent, the compound represented by the general formula R ⁵ COY (wherein R ⁵ is a C ₁ -C ₄ alkyl group or C ₁ -C
_{4 is} an alkoxyl group, Y is a halogen atom, OCOR ⁵
Alternatively, it represents OSO ₂ R ⁶ (R ⁶ represents alkyl, haloalkyl or aryl). ) Is reacted with a compound of formula (2) (Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the same meanings as described above), and the compound is then added to a solvent in the presence of an azo compound, a peroxide and oxygen. By reacting with a hydrogen halide under at least one condition selected from under and under light irradiation. (Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same as above, and X is a halogen atom), and the compound is treated with a base in a solvent. General formula (4) characterized by processing (Wherein R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above). 2. A compound represented by the general formula (1): (Wherein R ¹ , R ² , R ³ and R ⁴ have the same meanings as described above), the compound represented by the general formula R ⁵ COY Wherein R ⁵ and Y have the same meanings as described above) and are reacted with a compound represented by the general formula (2): (In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same as defined above). 3. A compound represented by the general formula (2): (Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same as above), the compound is represented by an azo compound in a solvent,
The compound of the general formula (3) is characterized by reacting with hydrogen halide under at least one condition selected from the presence of peroxide, oxygen and under light irradiation. (In the formula, R ¹ , R ¹ , R ³ , R ⁴ , R ⁵ and X are the same as defined above.) 4. A compound represented by the general formula (3): (Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are the same as defined above), the compound is treated with a base in a solvent. (4) [Chemical Formula 10] (In the formula, R ¹ , R ² , R ³ and R ⁴ are the same as defined above.) A process for producing a compound represented by the formula. 5. A compound represented by the general formula (2): (In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same as defined above). 6. R ¹ is a methyl group and R ² is tert.
A butyl group, R ³ and R ⁴ are hydrogen atoms,
The compound according to claim 5, wherein R ⁵ is a methyl or methoxyl group. 7. A compound represented by the general formula (3): (In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and X are the same as defined above). 8. R ¹ is a methyl group and R ² is tert.
-Butyl group, R ³ and R ⁴ are hydrogen atoms, and R
The compound according to claim 7, wherein ⁵ is a methyl or methoxyl group and Y is bromine.