JPH093055A - Production of chromanone compound - Google Patents

Abstract

PURPOSE: To obtain a chromanone compound in a short time as a synthetic intermediate for chromene compounds useful as a photochromic compound by reaction between two specific compounds at a specific ratio in the presence of a condensing agent. CONSTITUTION: The condensation reaction between a compound of formula I (R1 -R4 are each H or a substituent, they may form a 5-8 membered ring containing nonmetallic elements) and a compound of formula II (R5 and R6 are each an aryl or a heterocycylic ring group or they may bond to each other to form a ring) is carried out in the presence of (C) a condensing agent, preferably a sodium alcoholate, particularly preferably sodium tert.-butylate, using a 1-10 equivalent amount of the component B per one equivalent of the component A, to produce the objective chromanone compound. In this reaction, an intermediate of formula IV (M is a mono- or divalent metal) can be isolated.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a chromanone compound, which is an important intermediate in the production of a chromene compound useful as a photochromic compound.

[0002]

2. Description of the Related Art Chromanone compounds in which the 2-position is substituted with a diaryl group are described in J. C. S. , 5261 (196
5). C. S. , 5228 (1964) and the like, but they had drawbacks such as using a large amount of the starting diaryl ketone, a long reaction time, and time-consuming purification.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel method for producing a chromanone compound, which overcomes the above-mentioned deficiencies.

[0004]

The objects of the present invention have been achieved by the following method. That is, the present invention is a method for producing a chromanone compound represented by the general formula (3) by reacting a compound represented by the general formula (1) with a compound represented by the general formula (2) in the presence of a condensing agent. A method for producing a compound represented by the general formula (1), wherein the compound represented by the general formula (2) is used in an amount of 1 to 10 equivalents.

[0005]

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In the formula, R ¹ , R ² , R ³ and R ⁴ each represent a hydrogen atom or an organic group. R ¹ , R ² , R ³ ,
R ⁴ may be mutually cyclized at adjacent positions to form a saturated or unsaturated ring composed of a 5- to 8-membered non-metal atom. R
⁵ and R ⁶ represent an aryl group or a heterocyclic group. R ⁵ and R
⁶ may combine with each other to form a ring. Alternatively, in the method for producing the chromanone compound represented by the general formula (3), the compound represented by the general formula (1) is reacted with the compound represented by the general formula (2) in the presence of a condensing agent. A method for producing, characterized in that the intermediate represented by (4) is isolated.

[0007]

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Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R
⁶ is synonymous with the above definition. M represents a monovalent or divalent metal.

Further explanation of the above general formulas (1) to (4)
I will tell. R¹, R^Two, R^Three, R^FourThe substituent of is a halogen atom
Child, optionally substituted alkyl group, substituted
Optionally aryl group, optionally substituted alkoxy
Group, acyl group, acylamino group, sulfonyl group, substituted
Optionally substituted amino group, carboxyl group, sulfo group
Group, cyano group, perfluoroalkyl group, alkanesul
Selected from phenyl, thioalkyl, nitro, etc.
You. Further, they are cyclized with each other at adjacent positions and have a size of 5-8.
A saturated or unsaturated ring composed of non-metal atoms
May be. In particular, the case of an aromatic ring which may be condensed is preferable.
Good. For example, cyclohexene, cyclopentene, a
Dulene, benzene, naphthalene, pyridine, pyrimidii
, Quinoline, imidazole, indole, furan, chi
Offen, indazole, benzimidazole, naphtho
Thiophene, naphthopyran, pyrene, anthracene, na
A cyclic structure such as futoquinoline may be mentioned as an example.
R^FiveAnd R⁶Is benzene, naphthalene, pyridine,
Norrin, imidazole, furan, thiophene, benzii
Midazole, naphthothiophene, naphthopyran, pyret
, Anthracene, naphthoquinoline and the like.
These are R¹, R ^Two, R^Three, R^FourSubstituents described in (cyclic
(Including the structure). R ^FiveAnd R⁶Are
They may be bonded to each other to form a ring. R^FiveAnd R⁶Joins
In the case of
Or by a single bond. -CR^Five(R⁶)-Example below
It was shown to.

[0010]

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[0011]

[Chemical 6]

In the formula, Me represents a methyl group and Ph represents a phenyl group. These may be substituted by the substituents described above. Preferred among R ⁵ and R ⁶ is substituted or unsubstituted benzene. Examples of M include alkali metals and alkaline earth metals. Alkali metals are preferred, especially sodium. Specific examples of the compound represented by formula (1) are shown below.

[0013]

[Chemical 7]

In the formula, Et represents an ethyl group and Bu represents a butyl group. Specific examples of the compound represented by the general formula (2) are shown below.

[0015]

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Specific examples of the compound represented by the general formula (4) are compound No. 1-1 to 1-16 and compound No. 2-1 to 2.
Examples thereof include those in which -18 is combined and dehydrated and condensed to form a metal salt (sodium salt, potassium salt, etc.).
Of the metal salts, the sodium salt is most preferred. A specific example will be described later.

The condensing agent used in the present invention is a basic compound,
For example, alkali metal alcoholates (eg, sodium or potassium methylate, ethylate, isopropylate, tertiary butyrate, etc.), amides (eg, sodium amide, lithium amide, lithium diisopropylamide, N-lithium (2,2,6,2). 6-tetramethyl) piperidine, etc.), lithium alkyl (eg tertiary butyl lithium), alkali or alkaline earth metal hydrides (eg lithium hydride,
Sodium hydride, potassium hydride, calcium hydride, etc.). Among these, sodium alcoholate is preferable, and sodium tertiary butyrate is particularly preferable.

The condensing agent is used in a catalytic amount or a stoichiometric amount or a large excess amount with respect to the compound represented by the general formula (1). Preferably stoichiometric amounts up to 6 equivalents are used.

The molar ratio between the compound represented by the general formula (1) and the compound represented by the general formula (2) in the condensation reaction is 1 to 10, preferably 2 to 5.

The condensation reaction may be an aliphatic or aromatic hydrocarbon (eg pentane, hexane, heptane, benzene, toluene, xylene), a chlorinated aliphatic or aromatic hydrocarbon (eg Dichloromethane, 1,1-dichloroethane, chlorobenzene), aliphatic or aromatic ethers (eg, diethylene glycol dimethyl ether, diethyl ether, tetrahydrofuran, diphenyl ether), alcohols (eg, methanol, ethanol, isopropanol, n-).
It is carried out in the presence of a suitable solvent selected from butanol, t-butanol), amides (eg dimethylformamide), dimethylsulfoxide, mixtures of two or more of these solvents.

The condensation reaction is carried out at a temperature of 0 to 200 ° C., preferably 50 to 120 ° C., and a reaction time of 1 minute to 60 hours, preferably 30 minutes to 20 hours.

After completion of the condensation reaction, the reaction mixture is treated with an acid (for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphonic acid, acetic acid or a mixture thereof) to give a chromanone compound represented by the general formula (3). can get. At this time, it is better to isolate the compound represented by the general formula (4) from the reaction mixture after completion of the condensation reaction, and then treat the compound with the above-mentioned acid in the presence of a suitable solvent (eg, methanol, ethanol, isopropanol). preferable.

[0023]

EXAMPLES The method of the present invention will be described below with reference to examples, but this is only one example and the present invention is not limited thereto. Example 1 Synthesis of chromanone 1

[0024]

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Compound No. 1-1, 5.36 g (0.02)
88 mol), Compound No. 2-1 10.49 g (0.0
576 mol) and 100 ml of benzene, and a solution of sodium t-butoxide (2.2 g of sodium metal)
(Prepared from 0.096 mol) and 40 ml of t-butanol)
The mixture was heated to reflux for 3 hours while stirring. The reaction mixture was poured into 400 ml of methanol and 30 ml of 47% hydrobromic acid and heated under reflux for 3 hours. After distilling off the solvent, the residue was purified by silica gel column chromatography (developing solvent benzene) and crystallized with hexane 1, and chromanone 1 at mp 170 to 171 ° C.
Was obtained 8.87 g (yield 87%).

Example 2 Synthesis of chromanone 1 5.36 g (0.0288 mol) of compound No. 1-1,
Compound No. 2-1 10.49 g (0.0576 mol)
And a solution of 100 ml of benzene was added to sodium t-
Butoxide solution (2.2 g of sodium metal (0.096
Mol) and 40 ml of t-butanol) and heated under reflux for 3 hours while stirring. The reaction mixture was cooled to 5 ° C., and the obtained crystals of compound No. 4-1 were collected by filtration.

[0027]

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The crystals were added to 100 ml of methanol and 15 ml of 47% hydrobromic acid and heated under reflux for 3 hours. The reaction mixture was stirred in an ice bath for 1 hour and the crystals were collected by filtration. The crystals were chromanone 1mp 169-171 ° C. Yield 8.
95 g (yield 90.0%).

Comparative Example 1 Synthesis of chromanone 1 (JCS, 5261 (196)
Method 5)) 5.36 g (0.0288 mol) of Compound No. 1-1,
A solution consisting of 54.6 g (0.300 mol) of Compound No. 2-1 and 450 ml of benzene was added with a sodium t-butoxide solution (5 g (0.22 mol) of metallic sodium and t).
-Butanol (prepared from 40 ml) and heated to reflux for 20 hours while stirring. This was poured into a mixture of 100 ml of hydrobromic acid and 150 ml of acetic acid while stirring. After separating the benzene layer, steam distillation was performed to remove the starting material. The remaining brown solid was purified by alumina chromatography (developing solvent benzene). After the solvent was distilled off, crystallization was performed from light oil (bp 100 to 120 ° C) to obtain 8.58 g (yield 85%) of chromanone-1 having an mp of 169 to 171 ° C.

It is apparent that Examples 1 and 2 of the present invention are superior to Comparative Example 1 in reaction time, operability, and not using a large excess of the raw material compound No. 2-1. . In particular, since Example 2 does not require the use of chromatography for purification, it can be said that it is far more suitable for mass synthesis.

Example 3 Synthesis of chromanone 2

[0032]

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Compound No. 1-2 2.65 g (0.01
42 mol), Compound No. 2-1 10.35 g (0.0
A solution of 568 mol) and 150 ml of benzene was added to a sodium t-butoxide solution (3.0 g of sodium metal).
(Prepared from 0.13 mol) and 40 ml of t-butanol) and heated under reflux for 10 hours while stirring. The reaction mixture was cooled to 5 ° C., and the obtained crystals of compound No. 4-2 were collected by filtration.

[0034]

[Chemical 12]

This crystal was mixed with 100 ml of ethanol and DMAC.
The mixture was added to 100 ml and 40 ml of 47% hydrobromic acid and heated under reflux for 10 hours. 100 ml of water was added to the reaction mixture, and the mixture was stirred in an ice bath for 1 hour, and the crystals were collected by filtration. This crystal is chromanon 2, m
It was p179-181 degreeC. Yield 3.33 g (yield 6
7%).

Comparative Example 2 Synthesis of Chromanon 2 (JCS, 5261 (196)
Method 4)) Compound No. 1-2 2.65 g (0.0142 mol),
A solution consisting of 32.0 g (0.176 mol) of Compound No. 2-1 and 300 ml of benzene was added to a sodium t-butoxide solution (3 g of metal sodium (0.13 mol) and t).
-Prepared from 25 ml of butanol) and heated to reflux for 20 hours while stirring. This was poured into a mixture of 75 ml hydrobromic acid and 50 ml acetic acid while stirring. After separating the benzene layer, steam distillation was performed to remove the starting material. The remaining orange gum was purified by alumina chromatography (developing solvent benzene). After distilling off the solvent, it was crystallized from light oil (bp 100 to 120 ° C.) to obtain chromanone 2 having an mp of 180 to 181 ° C.
86 g (yield 57%) was obtained.

In contrast to Comparative Example 2 described above, Example 3 of the present invention is suitable for large-scale synthesis because of its operability, in particular, it is not necessary to use chromatography for purification, and raw material compound No. 2-1 is not used in large excess. Is clearly much better. Example 4 Synthesis of chromanone 3

[0038]

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Chromanone 3 was obtained from compound No. 2-1 and compound No. 2-2 in the same manner as in Example 2.

Example 5 Synthesis of chromanone 4

[0041]

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Chromanone 4 was obtained from compound No. 2-1 and compound No. 2-3 in the same manner as in Example 2.

Example 6 Synthesis of chromanone 5

[0044]

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Chromanone 5 was obtained from compound No. 2-1 and compound No. 2-6 in the same manner as in Example 2.

Example 7 Synthesis of chromanone 6

[0047]

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Chromanone 6 was obtained from compound No. 2-1 and compound No. 2-7 in the same manner as in Example 2.

The compound represented by the general formula (3) can be produced by the same method. Specific examples are given below.

[0050]

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[0051]

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─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area C07D 493/10 C07D 493/10 C 493/20 493/20 495/20 495/20 // C09K 9 / 02 C09K 9/02 B

Claims (2)

[Claims] 1. A method for producing a chromanone compound represented by the general formula (3) by reacting a compound represented by the general formula (1) with a compound represented by the general formula (2) in the presence of a condensing agent. A method for producing a chromanone compound, wherein the compound represented by the general formula (1) is used in an amount of 1 to 10 equivalents relative to the compound represented by the general formula (1). Embedded image In the formula, R ¹ , R ² , R ³ and R ⁴ each represent a hydrogen atom or a substituent. R ¹ , R ² , R ³ and R ⁴ may be mutually cyclized at adjacent positions to form a saturated or unsaturated ring composed of a 5- to 8-membered non-metal atom. R ⁵ and R ⁶ represent an aryl group or a heterocyclic group. R ⁵ and R ⁶ may combine with each other to form a ring. 2. A method for producing a chromanone compound represented by the general formula (3) by reacting a compound represented by the general formula (1) with a compound represented by the general formula (2) in the presence of a condensing agent. A method for producing a chromanone compound, comprising isolating the intermediate represented by the general formula (4). Embedded image In the formula, R ¹ , R ² , R ³ and R ⁴ each represent a hydrogen atom or a substituent. R ¹ , R ² , R ³ and R ⁴ may be mutually cyclized at adjacent positions to form a saturated or unsaturated ring composed of a 5- to 8-membered non-metal atom. R ⁵ and R ⁶ represent an aryl group or a heterocyclic group. R ⁵ and R ⁶ may combine with each other to form a ring. M represents a monovalent or divalent metal.