JP2834616B2 - Method for producing chromene compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a highly pure chromene compound from a chromanol compound.

[0002]

2. Description of the Prior Art It has been known that alumina or thorium dioxide is used as a catalyst for alcohol dehydration. In these reactions, the amount of alumina or thorium dioxide used is a catalytic amount, for example, about 1% by weight, based on the alcohol used as the raw material.

[0003]

DISCLOSURE OF THE INVENTION The present inventors have attempted a dehydration reaction using the above-mentioned catalytic amount of alumina or thorium dioxide in order to produce a chromene compound from a chromanol compound. As a result, there has been a problem that the purity of the chromene compound is not sufficient and the produced chromene compound is colored.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, dehydration was carried out in the presence of an amount of alumina which greatly exceeded the amount of catalyst with respect to the starting chromanol compound. By carrying out the reaction, a method for producing a chromene compound with high purity and no color was found, and the present invention was completed.

That is, the present invention provides a compound represented by the general formula (1):

[0006]

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Wherein the chromanol compound is subjected to a dehydration reaction in an organic solvent in the presence of 50 to 1000 parts by weight of alumina with respect to 100 parts by weight of the chromanol compound.

[0008]

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[0009] The method for producing a chromene compound shown in the above.

The chromanol compound used in the present invention is generally represented by the following formula (1).

[0011]

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(However,

[0013]

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Is an optionally substituted aromatic hydrocarbon group or unsaturated heterocyclic group, and R ₁ , R ₂ and R ₃
Are respectively the same or different hydrogen atoms, alkyl groups, amino groups or substituted amino groups, of which R ₁ and R ₂
May together form a ring. ) In the general formula (1),

[0015]

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The group represented by is an optionally substituted aromatic hydrocarbon group or unsaturated heterocyclic group. Specific examples of the aromatic hydrocarbon group include a benzene ring such as a benzene ring, a naphthalene ring, a phenanthrene ring, and an anthracene ring.
Valence groups. Further, the above aromatic hydrocarbon group may be substituted with a substituent.

Specific examples of the unsaturated heterocyclic group include divalent groups derived from a bicyclic unsaturated heterocyclic ring such as a quinoline ring, an isoquinoline ring, a benzothiophene ring, a benzofuran ring and an indole ring. No. Further, the above unsaturated heterocyclic group may be substituted with a substituent.

Examples of the substituent of the aromatic hydrocarbon group or the unsaturated heterocyclic group include halogen atoms such as fluorine, chlorine, bromine and iodine; hydroxyl group; cyano group; nitro group; amino group; A methylamino group; an alkylamino group having 1 to 4 carbon atoms such as a diethylamino group;
A lower alkyl group having 1 to 4 carbon atoms such as a propyl group and a t-butyl group; a halogenated lower alkyl group having 1 to 3 halogen atoms such as a trifluoromethyl group and a 2-chloroethyl group; A lower alkoxy group having 1 to 4 carbon atoms such as methoxy group, ethoxy group and t-butoxy group; an aryl group having 6 to 10 carbon atoms such as phenyl group, naphthyl group and tolyl group; a phenoxy group and 1-naphthoxy group An aryloxy group having 6 to 14 carbon atoms; an aralkyl group having 7 to 15 carbon atoms such as benzyl group, phenylethyl group and phenylpropyl group; an aralkoxy group having 7 to 15 carbon atoms such as benzyloxy group and phenylpropoxy group; And an alkylthio group of the formulas 1-4. further,

[0019]

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Wherein R ₅ is an alkylene group or — (O—R
₈ ) n- (where R ₈ is an alkylene group and n is a positive integer), R ₆ and R ₇ are the same or different alkyl groups, and X is

[0021]

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## EQU1 ## ｝ May be substituted one or more times. The carbon number of the alkyl group and the alkylene group is preferably in the range of 6 to 20, and n is preferably an integer such that the total carbon number is 6 to 20. These substituents may be the same or different, and the substitution position is not particularly limited.

Next, in the above general formula (1), R ₁ , R ₂ and R ₃ are the same or different hydrogen atoms, alkyl groups, amino groups or substituted amino groups, respectively, and R ₁ and R ₂
And may form a ring together. In this case, the ring is generally preferably a cycloalkyl ring having 5 to 10 carbon atoms, a bicycloalkyl ring, or a tricycloalkyl ring.
When these are exemplified more specifically, a cyclopentyl ring,
And a divalent group derived from a cyclohexyl ring, a cycloheptyl ring, a norbornane ring, an adamantane ring, and a bicyclo [3.3.1] nonane ring.

Specific examples of chromanol compounds that can be suitably used in the present invention are as follows.

(1) Spiro [norbornane-2,2'-
4-benzo [h] chromanol] (2) spiro [bicyclo [3.3.1] nonane-9,
2'-4-benzo [f] chromanol] (3) 4'-methylspiro [bicyclo [3.3.1] nonane-9,2'-4-benzo [f] chromanol] (4) 3'-methylspiro [ Norbornane-2,2'-
4-benzo [f] chromanol] (5) 2,2-dimethyl-7-octoxy-4-benzo [h] chromanol] (6) spiro [tricyclo [3.3.1.1 ^3,7 ] decane-2 , 2'-4-benzo [h] chromanol] (7) 4'-piperidinospiro [bicyclo [3.3.
1] Nonane-9,2'-4-benzo [h] chromanol] (8) 2,2-dimethyl-6-octadecyl-4-benzo- [h] chromanol (9) Spiro [norbornane-2,2'- 4-naphtho [1,2-h] chromanol] (10) 2,2-dimethyl-7- (ethylthiohexyl)
Oxy-4-benzo [h] chromanol (11) 6-chloro-2,2-dimethyl-7- (dipropylphosphonohexyl) oxy-4-benzo [h] chromanol (12) 2,2-dimethyl-4 -Pyrido [2,3-h] chromanol (13) 7-methoxy-2,2-dimethyl-4-benzo [h] chromanol (14) 7- (diethylaminooctyl) -2,2-dimethyl-4-benzo [ h] Chromanol The alumina used in the present invention is not particularly limited, but generally, those having fine particles and high activity are preferably used. For example, the average particle size is 50 to 200 μ
Activated alumina in the range of m is preferred. Also, 50
p of the supernatant when 5 g of alumina was dispersed in cc of water
Activated alumina having H of 3 to 10, preferably 4 to 6, is suitably used.

The amount of the above-mentioned alumina to be used must be at least 50 parts by weight, preferably at least 70 parts by weight, based on 100 parts by weight of the raw material chromanol compound. When the amount of alumina is less than 50 parts by weight, it is impossible to produce a non-colored and high-purity chromene compound. On the other hand, although the use of a large amount of alumina does not significantly affect the purity of the chromene compound, it is economically disadvantageous.

The dehydration reaction in the present invention is preferably performed in an organic solvent. The organic solvent used is not particularly limited, but generally a non-polar organic solvent is preferably used. More specifically, for example, aliphatic hydrocarbons such as hexane, heptane and pentane; aromatic hydrocarbons such as benzene, toluene and xylene; carbon tetrachloride, chloroform,
Halogenated hydrocarbons such as ethylene chloride and chlorofluorocarbon; ether compounds such as isopropyl ether and diethyl ether;

The reaction method is not particularly limited, and a known dehydration reaction method can be employed as it is. For example, a method can be employed in which a chromanol compound and alumina are added to a solvent, and the mixture is heated to near the boiling point of the solvent and dehydrated. The reaction temperature is usually from 100 to 150 ° C., and the reaction time is 1 hour.
It can be adopted from a range of 10 hours. In this way, a highly pure and colorless chromene compound can be produced.

The chromene compound has the general formula (1)
Is a dehydrated compound, and is generally represented by the following formula (2).

[0030]

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Where R ₁ , R ₂ , R ₃ and

[0032]

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Is the same as the above equation (1). ｝

[0034]

As described above, the chromene compound can be obtained with high purity and no color by the production method of the present invention.

[0035]

EXAMPLES The present invention will be described below in more detail with reference to typical examples, but the present invention is not limited to these examples.

Example 1 A chromanol compound of the following formula was placed in a vessel equipped with a stirrer, thermometer and reflux condenser.

[0037]

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After supplying 27.9 g and heptane 150 ml, activated alumina (PH = 4.5, average particle size 1)
(50 μm) was added and stirred. After raising the inside of the vessel to the reflux temperature, the mixture was stirred for 4 hours. After completion of the reaction, the temperature in the vessel was lowered to 25 ° C., and the alumina was filtered. Next, heptane was expelled by an evaporator and crystallized and dried with a mixed solvent of methanol and acetone to obtain 21.0 g of a white chromene compound represented by the following formula. The product was analyzed by liquid chromatography to find a purity of 9
9%.

[0039]

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Examples 2 to 4 and Comparative Example The same procedures as in Example 1 were carried out except that the amount of alumina was changed to the amount shown in Table 1. The results are shown in Table 1.

[0041]

[Table 1]

Examples 5 to 6 The procedure of Example 1 was repeated, except that the activated alumina shown in Table 2 was used (the average particle diameter was 150 μm in each case). The results are shown in Table 2. In each case, the chromene compound was white.

[0043]

[Table 2]

Examples 7 to 11 The procedure of Example 1 was repeated, except that the chromanol compound was changed to the chromanol compound shown in Table 3. The results are shown in Table 3. In each case, the chromene compound was white.

[0045]

[Table 3]

Examples 12 to 14 The same procedures as in Example 1 were carried out except that heptane was changed to the organic solvent shown in Table 4. The results are shown in Table 4. In each case, the chromene compound was white.

[0047]

[Table 4]

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI C07D 495/04 101 C07D 495/04 101 // C07B 61/00 300 C07B 61/00 300 (56) References Chemical Society of Japan New Experimental Chemistry Lecture 14 Synthesis and Reaction of Organic Compounds (I) "(1972-1974) Maruzen pp. 119-122 Morrison Boyd" Organic Chemistry (1) Third Edition "(1977-2-1) Tokyo Chemistry Doujin, p. Chem. Soc. , Perkin Trans. 1, [4] (1983) p. 827-830, “Large Organic Chemistry, Vol. 14, Heterocyclic Compounds I” (Showa 40-10-30), Asakura Shoten, p. Heterocyclic Chem. , 29 [6] (1992) p. 1457-1460 (58) Fields surveyed (Int. Cl. ⁶ , DB name) C07D 311/22-311/96 C07D 491/052-495/04 101 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. A compound of the general formula (1) Wherein the chromanol compound is subjected to a dehydration reaction in an organic solvent in the presence of 50 to 1000 parts by weight of alumina with respect to 100 parts by weight of the chromanol compound represented by the general formula (2). And a method for producing a chromene compound.