JP2002205963A - New naphthalene compound having reaction-active group and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain new naphthalene compounds, and to provide a method for producing these compounds. SOLUTION: A synthesis route comprises a series of the following step processes: obtaining a 1-halogeno-3,7-bis(trifluoromethyl)naphthalene from 2,6- bis(trifluoromethyl)naphthalene; obtaining 1-hydroxymethyl-3, 7- bis(trifluoromethyl)naphthalene through the 1-halogeno-3,7-bis(trifluoromethyl) naphthalene, and converting the hydroxy group into a releasing group and then reacting the releasing group with a cyanide ion to obtain the objective 1-cyanomethyl-3,7-bis(trifluoromethyl)naphthalene. The final product: 1- cyanomethyl-3,7-bis(trifluoromethyl)naphthalene, is useful as a precursor for organic fluorescent substances, and the like, and the other intermediate products are also useful as intermediates for wide uses.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

FIELD OF THE INVENTION The present invention relates to novel naphthalene compounds, specifically to fluorine-containing naphthalene compounds,
And their production methods. The novel compounds of the present invention are useful as precursors for organic fluorescent substances, liquid crystal materials, and dyes, and are expected to be widely used as various other intermediates.

[0002]

2. Description of the Prior Art The naphthalene compounds according to the invention are novel and, therefore, the process for preparing them is also novel.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide novel naphthalene compounds represented by the following general formula (I) and methods for producing them.

[0004]

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That is, the present invention relates to a novel 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene represented by the following formula (V) and a 1-halogeno represented by the formula (III) as a precursor thereof. -3,7-bis (trifluoromethyl) naphthalene [the halogen atom at the 1-position is F, Cl, B
r, or I], and 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (IV). The novel 1-cyanomethyl-3,7- represented by the formula (V) provided by the present invention
Bis (trifluoromethyl) naphthalene has high reactivity with various compounds due to having active methylene, and is expected to be useful for producing organic fluorescent substances, dyes, liquid crystal materials, etc. having a trifluoromethyl group. Intermediate compound. Also, 1-halogeno-3,7-bis (trifluoromethyl) naphthalene represented by the formula (III) and 1-hydroxymethyl-3,7 represented by the formula (IV)
-Bis (trifluoromethyl) naphthalene has the formula (V)
Not only useful as a precursor of the compound of formula (I), but also because each has a reactive halogen atom and a hydroxymethyl group, it is an intermediate for the production of medical and agricultural chemicals having a trifluoromethyl group, functional materials, etc. It is a useful compound that is expected to be applied in a wide range of fields.

[0006]

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[0007]

Means for Solving the Problems The present inventors have found that the formula (V)
A novel 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (II) is used as a starting material, and a novel 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (II) And a method for producing the compound via 1-halogeno-3,7-bis (trifluoromethyl) naphthalene and 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (IV). Was.

A specific method for producing the novel compounds of the present invention will be described in detail below. 2,6-bis (trifluoromethyl) naphthalene represented by formula (II), readily available 2,6-naphthalenedicarboxylic acid can be produced by fluorinating with a fluorinating agent such as SF _4.

By directly halogenating 2,6-bis (trifluoromethyl) naphthalene represented by the formula (II), 1-halogeno-3,7, a novel naphthalene compound represented by the formula (III), is obtained. -Bis (trifluoromethyl) naphthalene can be produced. In view of the yield of this direct halogenation reaction and the yield of the next step [production of the compound of the formula (IV)], the novel 1-halogeno-3,7-bis (trifluoromethyl) represented by the formula (III) It is preferable and recommended that the halogen at the 1-position of naphthalene be a bromine atom.

Therefore, 1-bromo-3,7-bis (trifluoromethyl) naphthalene wherein the halogen in the formula (III) is a bromine atom [compound represented by the formula (VI)]
The manufacturing method of the will be described below. <Method for Producing 1-Bromo-3,7-bis (trifluoromethyl) naphthalene> A method for producing a target compound of the formula (VI) from a starting compound of the following formula (II) is as follows. The compound of formula (VI) can be prepared by directly brominating the compound of formula (II).

[0011]

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Bromine is added dropwise to 2,6-bis (trifluoromethyl) naphthalene of the formula (II) in the presence of an iron-based catalyst at a predetermined temperature and for a predetermined time using a solvent without a solvent, or By reacting, 1-bromo-3,7-bis (trifluoromethyl) naphthalene which is a novel naphthalene compound represented by the formula (VI) can be produced.

The raw material represented by the formula (II) is free of a solvent,
Alternatively, it is preferable to use it after diluting it with a chlorine-based solvent such as dichloromethane or chloroform. The amount of the solvent used is 0 to 20 ml per 1 g of the raw material. Since this raw material has a trifluoromethyl group on the naphthalene ring, it has low reactivity to bromine, and it is preferable to use a catalyst. As the catalyst, an iron-based catalyst is preferable,
Iron powder, iron (III) bromide and the like can be used. The amount used is preferably 0 to 0.2 times the molar amount of the raw material. As for bromine, it can be used without dilution. The amount used is 0.9-1.
It is 5 times the molar amount. Bromine It is preferable to drop the solution in 0.5 to 5 hours.
Continue stirring for hours. The reaction temperature during and after the dropping of bromine is preferably in the range of 0 to 150 ° C. The bromination reaction can be performed under normal pressure, but may be performed under pressure. After completion of the reaction, a usual naphthalene compound represented by the formula (VI) 1-
Bromo-3,7-bis (trifluoromethyl) naphthalene can be produced. <Production of 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene> Starting from 2,6-bis (trifluoromethyl) naphthalene represented by the aforementioned formula (II) as a raw material, 1-halogeno-3,7-bis (trifluoromethyl) naphthalene represented by 1-hydroxymethyl- represented by the formula (IV)
As a method for producing 3,7-bis (trifluoromethyl) naphthalene, a compound represented by the formula (II) under an inert gas atmosphere is used.
It can be produced by preparing an organometallic compound from the compound of I) and reacting it with formaldehyde.

Here, in the compound of the formula (III), X
Is 1-bromo-3,7-bis (trifluoromethyl) naphthalene represented by the formula (VI), and a compound of the formula (IV) is produced from the compound of the formula (VI) As a method, it can be produced by preparing an organometallic compound from the compound of the formula (VI) under an inert gas atmosphere and reacting the compound with formaldehyde.

[0015]

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1-bromo-3,7 represented by the formula (VI)
A solution containing an organometallic compound is prepared by reacting an organolithium reagent or metallic magnesium with bis- (trifluoromethyl) naphthalene in a solvent at a predetermined temperature and for a predetermined time with stirring, and agitating the solution and formaldehyde. By reacting at a predetermined temperature and for a predetermined time, 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene, which is a novel naphthalene compound represented by the formula (IV), can be produced. Since this reaction is a reaction that dislikes moisture, it is preferable to perform the reaction in a reaction vessel under an atmosphere of a dry inert gas such as nitrogen.

As a solvent for this reaction, ether solvents such as diethyl ether and tetrahydrofuran can be used. The amount used is preferably 1 to 100 ml per 1 g of raw material.

When the organolithium reagent is allowed to act,
Usually, it is necessary to perform at low temperature. The temperature is between -80 ° C and 0
C is preferred. When metallic magnesium is allowed to act, the temperature is preferably about -30C to 50C. The amount of the organic lithium reagent and the metal magnesium used is preferably 1 g of the raw material.
1 to 2 times the molar amount of The solution containing the prepared organometallic compound is reacted with formaldehyde,
As the formaldehyde, paraformaldehyde (solid) may be directly added, or formaldehyde (gas) generated by thermally decomposing paraformaldehyde in a separate container may be used. The amount used is 1 to 3 times the molar amount of the raw material. The reaction with formaldehyde is preferably carried out at a temperature between -50C and 30C. The reaction time is preferably 0.5 to 5 hours. After completion of the reaction, dilute sulfuric acid, dilute hydrochloric acid, and the like are added dropwise at a temperature not higher than room temperature, and ordinary post-treatment and purification are performed, whereby 1-hydroxymethyl-3,7, a novel naphthalene compound represented by the formula (IV), is obtained.
-Bis (trifluoromethyl) naphthalene can be produced. <Production method of 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene> 2,2 represented by the formula (II)
Starting from 6-bis (trifluoromethyl) naphthalene, 1-halogeno- represented by formula (III)
Via 3,7-bis (trifluoromethyl) naphthalene and 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene of the formula (IV), a novel compound of the formula (V) As a method for producing 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene, a compound of the formula (IV) is produced from a compound of the formula (II) by the above-mentioned method route, and further, the reaction is carried out in an inert atmosphere. The compound of the formula (IV) can be produced by converting a hydroxyl group into a leaving group and then reacting the compound with a cyanide ion.

As a method for producing the compound of the formula (V) from the compound of the following formula (IV), the compound of the formula (I) is prepared under an inert gas atmosphere.
A novel naphthalene compound of the formula (V) can be produced by converting a hydroxyl group of the compound of V) into a leaving group and reacting the compound with a cyanide ion.

[0020]

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The hydroxy group (hydroxyl group) of 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (IV) is stirred in a solvent at a predetermined temperature,
The solution is converted into a leaving group by reacting with an appropriate reagent in a predetermined time, and the solution is reacted with a cyanide ion at a predetermined temperature and a predetermined time under stirring to obtain a novel 1-type compound represented by the formula (V). Cyanomethyl-3,7-bis (trifluoromethyl) naphthalene can be produced. Since this reaction is a reaction that dislikes moisture, it is preferable to perform the reaction in a reactor under an atmosphere of a dry inert gas such as nitrogen.

The leaving group is preferably a p-toluenesulfonyl group, a methanesulfonyl group, a trifluoromethanesulfonyl group, a halogen atom or the like. As the sulfonylating agent, the corresponding acid chloride or acid anhydride can be used. As the halogenating agent, a hydrohalic acid, a halide of an inorganic acid or the like can be used. The amount of these reagents used is preferably 1 to 3 times the molar amount of the raw materials. In the sulfonylation reaction, the same amount or slightly excess of base as the sulfonylating agent, for example, triethylamine,
It is preferably carried out in the presence of a tertiary amine such as pyridine. The reaction temperature and reaction time for sulfonylation and halogenation vary depending on the reagent, but it is usually preferable to carry out the reaction at a temperature of -20 ° C to 100 ° C.

The resulting compound having a leaving group is dissolved in a polar solvent and reacted with a cyanating agent. As the polar solvent, dimethyl sulfoxide, dimethylformamide,
N-methylpyrrolidone, acetone and the like can be used. The amount used is preferably 1 to 100 ml per 1 g of the compound having a leaving group. As the cyanating agent, sodium cyanide, potassium cyanide and the like can be used. The amount used is preferably 1 to 2 times the molar amount of the compound having a leaving group. The reaction temperature for cyanation is preferably from 0 to 150C. The reaction time is preferably 0.5 to 5 hours. After completion of the reaction, a normal naphthalene compound represented by the formula (V), 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene, can be produced by ordinary post-treatment and purification. .

An embodiment of the present invention will be described below. The method for producing the novel compounds in the present invention is not limited to those described in the examples.

[0025]

EXAMPLES 1-Bromo-3,7-bis (trifluoromethane
Example 1 Production of chill) naphthalene Example 1 2,6-bis (trifluoromethyl) naphthalene 5 was placed in a 300 ml glass flask equipped with an oil bath, a reflux condenser, a thermometer and a dropping funnel equipped with a pressure balance tube under a nitrogen atmosphere.
0 g (0.189 mol), 1 g (0.019 mol) of reduced iron powder and 100 ml of chloroform were charged. While stirring under reflux, 34.7 g (0.217 mol) of bromine was added dropwise over 2 hours. The by-produced hydrogen bromide gas was detoxified by an alkaline scrubber. After completion of the dropwise addition, stirring was continued for another 5 hours while heating under reflux. The stirring was stopped, and the reaction solution was cooled to room temperature as it was, filtered by suction, and the filtrate was washed with 100 ml of a 5% aqueous sodium sulfite solution and 100 ml of saturated saline. The organic phase was dried over anhydrous sodium sulfate, and after filtering off sodium sulfate, chloroform was distilled off under reduced pressure. The obtained crude product was purified by silica gel chromatography to give 1-bromo-3,7-
A pale yellow solid of bis (trifluoromethyl) naphthalene was obtained. LC purity 98%, yield 62.1 g (yield 95.7)
%).

The structure of the product was confirmed by nuclear magnetic resonance analysis and the like. Nuclear magnetic resonance analysis [Varian, Gemin
i200] were as follows. ¹ H-NMR (solvent: CDCl _3, standard: tetramethylsilane) δ 8.61ppm (s, 1H, Ar H) 8.81ppm (s, 1H, Ar H) 8.08ppm (d, J = 8. 64 Hz, 1 H, Ar H ) 8.05 ppm (s, 1 H, Ar H ) 7.82 ppm (d, J = 8.46 Hz, 1 H, Ar H ) ¹⁹ F-NMR (solvent: CDCl ₃ , standard: CFCl ₃₎ ) δ -62.43ppm (s, 3F, C F 3) -62.52ppm (s, 3F, C F 3) 1- hydroxymethyl-3,7-bis (trifluoromethanesulfonyl
Example 2 Production of tyl) naphthalene 1-bromo-3,7-bis (trifluoromethyl) naphthalene 3 in a 500 ml glass flask equipped with a cooling bath, a thermometer and a dropping funnel equipped with a pressure balance tube under a nitrogen atmosphere.
0 g (0.087 mol) and 150 ml of dry ether were charged. After cooling to −50 ° C. and stirring, 61.2 ml of an n-butyllithium hexane solution (1.54 M) (0.09
4 mol) was added dropwise over 30 minutes. Next, 7.9 g (0.26 mol) of paraformaldehyde was heated to 100 to 180 ° C. and heated in a separate glass flask under a nitrogen atmosphere with stirring to generate formaldehyde together with dry nitrogen in the main reaction flask. -50 ° C near the gas-liquid interface
Introduced over a period of 30 minutes while controlling within the range of -30 ° C. After the generation of formaldehyde is completed,
150 ml of water and concentrated hydrochloric acid
0 ml was slowly added dropwise. After dropping, add ether
The organic phase was extracted with 100 ml of a saturated saline solution.
And washed. The organic phase was dried over anhydrous sodium sulfate, and after filtering off sodium sulfate, chloroform was distilled off under reduced pressure.
The obtained crude product was purified by silica gel chromatography to obtain 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene as a white solid. LC
Purity: 99%, yield: 18.3 g (71.1%).

The structure of the product was confirmed by nuclear magnetic resonance analysis and the like. Nuclear magnetic resonance analysis [Varian, Gemin
i200] were as follows. ¹ H-NMR (solvent: CDCl ₃ , standard: tetramethylsilane) δ 8.44 ppm (s, 1H, Ar H ) 8.16 ppm (s, 1 H, Ar H ) 8.09 ppm (d, J = 5. 84Hz, 1H, Ar H) 7.84ppm (s, 1H, Ar H) 7.79ppm (dd, J = 1.60,8.60Hz, 1H, Ar H) 5.25ppm (s, 2H, C H 2 ) 2.05ppm (bs, 1H, O H) 19 F-NMR ( solvent: CDCl _{3, standard: CFCl 3) δ -62.26ppm (s} , 3H, C F 3) -62.60ppm (s, 3H , C F ₃₎ 1- cyanomethyl-3,7-bis (trifluoromethyl
3 ) Preparation of naphthalene Example 3 5 g of 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene was placed in a 100 ml glass flask equipped with a cooling bath, a thermometer and a dropping funnel equipped with a pressure balance tube under a nitrogen atmosphere. 0.017 mol), 3.45 g (0.034 mol) of triethylamine and 20 m of dichloromethane
l was charged. Under cooling and stirring at about 0 ° C., 2.95 g (0.026 mol) of methanesulfonyl chloride was added dropwise over 30 minutes. After completion of the dropwise addition, stirring was further continued at room temperature for 30 minutes. The mixture was cooled again to 0 ° C., and while stirring, 20 ml of a saturated sodium hydrogen carbonate solution was slowly added dropwise, followed by addition of 20 ml of dichloromethane and extraction. After completion of the dropwise addition, the organic phase was separated and washed with 20 ml of a saturated saline solution. The organic phase was dried over anhydrous sodium sulfate, sodium sulfate was filtered off, and chloroform was distilled off under reduced pressure. 6.0 g of a methanesulfonic acid ester was obtained as a pale yellow solid.

Next, 1.25 g (0.026 mol) of sodium cyanide and 30 ml of dimethyl sulfoxide were charged into a flask made of 100 ml equipped with an oil bath, a thermometer and a dropping funnel equipped with a pressure balance tube under a nitrogen atmosphere. , 70
Heated to ℃ to make a homogeneous solution. Here, the methanesulfonic acid ester prepared above was added to dimethyl sulfoxide 10 m
The solution dissolved in 1 was added immediately. After addition, 7
Stirred at 0 ° C. for another 30 minutes. After cooling, 100 ml of benzene was added to the reaction solution, and the mixture was washed with 50 ml of saturated saline. Separate the organic phase, dry over anhydrous sodium sulfate,
After filtering off sodium sulfate, benzene was distilled off under reduced pressure. The obtained crude product was purified by silica gel chromatography to obtain 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene as a pale yellow solid. LC purity 99%, yield 2.9 g (yield 56.3%).

The structure of the product was confirmed by nuclear magnetic resonance analysis and the like. Nuclear magnetic resonance analysis [Varian, Gemin
i200] were as follows. ¹ H-NMR (solvent: CDCl ₃ , standard substance: tetramethylsilane) δ 8.26 ppm (s, 1H, Ar H ) 8.23 ppm (s, 1 H, Ar H ) 8.17 ppm (d, J = 8. 60Hz, 1H, Ar H) 7.90ppm (s, 1H, Ar H) 7.87ppm (d, J = 8.60Hz, 1H, Ar H) 4.27ppm (s, 1H, C H 2) 19 F- NMR (solvent: CDCl ₃ , standard: CFCl ₃ ) δ 62.37 ppm (s, 3F, CF ₃ ) 62.62 ppm (s, 3F, CF ₃ )

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 255/35 C07C 255/35 // C07B 61/00 300 C07B 61/00 300 (72) Inventor Mitsuharu Shimoda 1497, Shibukawa-shi, Gunma, Kanto Denka Kogyo Co., Ltd. (72) Inventor Takahara 1497, Shibukawa-shi, Gunma Kanto Denka Kogyo Co., Ltd. Inside the Shibukawa Plant of Industrial Co., Ltd. (72) Inventor Tadao Nakaya 9 Kirihara-cho, Fujisawa-shi, Kanagawa Taiho Industrial Co., Ltd. Central Research Laboratory (72) Inventor Yuki Noguchi 9 Kirihara-cho, Fujisawa-shi, Kanagawa Prefecture Taiho Kogyo Co., Ltd. Institute in (72) inventor Akio Tajima Fujisawa, Kanagawa Prefecture Kirihara-cho, address 9 Taiho Industry Co., Ltd., Central Research Laboratory in the F-term (reference) 4H006 AA02 AC30 AC41 AC54 BB61 BE53 FC54 FE11 FE74 FE76 4H039 CA53 CD10

Claims (5)

[Claims] 1. A naphthalene compound represented by the following general formula (I). Embedded image 2. A novel naphthalene compound, 1-halogeno-3,7-bis of the following formula (III), which is obtained by directly halogenating 2,6-bis (trifluoromethyl) naphthalene of the following formula (II): A method for producing (trifluoromethyl) naphthalene. Embedded image 3. The following formula (II) obtained from 2,6-bis (trifluoromethyl) naphthalene of the following formula (II)
An organometallic compound is prepared from 1-halogeno-3,7-bis (trifluoromethyl) naphthalene of I) under an inert gas atmosphere and reacted with formaldehyde to obtain a novel naphthalene compound represented by the following formula ( IV)
Of producing 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene. Embedded image 4. A compound of the following formula (II) obtained from 2,6-bis (trifluoromethyl) naphthalene of the following formula (II):
Through 1-halogeno-3,7-bis (trifluoromethyl) naphthalene of I), 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene of the following formula (IV) is obtained, and its hydroxyl group is removed. After conversion into a leaving group, the compound is reacted with cyanide ion to obtain a novel naphthalene compound, 1-cyanomethyl-3,7- of the following formula (V).
A method for producing bis (trifluoromethyl) naphthalene. Embedded image 5. A bromination of 2,6-bis (trifluoromethyl) naphthalene of the following formula (II) directly in the presence of an iron-based catalyst to give 1-bromo-3,7-bis of the following formula (VI) A method for producing (trifluoromethyl) naphthalene. Embedded image