JP2941143B2 - Method for producing tetralin derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing a tetralin derivative.

[0002]

2. Description of the Related Art At present, a display device using a liquid crystal compound which is widely used is usually driven by a TN (twisted nematic) mode.

[0003] However, when this method is adopted,
In order to change the displayed image, it is necessary to change the position of the molecules of the liquid crystal compound in the device, which increases the driving time and the voltage required to change the molecular position of the liquid crystal compound, that is, consumption There is a problem that electric power also increases.

A switching element using a ferroelectric liquid crystal compound is a TN (twisted nematic) mode or an S-mode.
Unlike a switching element using a TN mode, the switching element can function as a switching element only by changing the alignment direction of the molecules of the liquid crystal compound, so that the switching time is significantly reduced. Further, since the value of Ps × E given by the spontaneous polarization (Ps) and the electric field strength (E) of the ferroelectric liquid crystal compound is the effective energy intensity for changing the orientation direction of the molecules of the liquid crystal compound, the power consumption is Is also very low.

[0005] Such a ferroelectric liquid crystal compound has two stable states, ie, bistability, depending on the direction of an applied electric field. Particularly suitable for use as a device or the like.

[0006] Antiferroelectric liquid crystals have these characteristics and are easy to realize a memory property and can easily achieve high contrast. Therefore, they are particularly suitable for use as display devices and the like.

When such a ferroelectric liquid crystal compound or an antiferroelectric liquid crystal compound is used for an optical switching element, the operating temperature range of the ferroelectric liquid crystal compound or the antiferroelectric liquid crystal compound is, for example, about room temperature. Alternatively, many characteristics are required, such as being lower than that, a wide operating temperature range, a high (fast) switching speed, and a switching threshold voltage within an appropriate range.

[0008] Among them, the operating temperature range is a particularly important characteristic when a ferroelectric liquid crystal compound or an antiferroelectric liquid crystal compound is put to practical use. However, among known ferroelectric liquid crystal compounds, for example, a paper by RB Meyer, et. Al., [J. de Phys., 36, L-69, 1975] , Masaaki Taguchi,
Takamasa Harada's paper [Preprints of the 11th LCD Discussion Meeting, 168 pages, 1985]
Year], the operating temperature is generally narrow,
Even a ferroelectric liquid crystal compound having a wide operating temperature range has not been practically satisfactory as a ferroelectric liquid crystal compound, for example, the operating temperature range is a high temperature range not including room temperature. Further, no practically satisfactory antiferroelectric liquid crystal compound has been obtained.

[0009]

Problems in the Prior Art The present inventors have found that a carboxylic acid ester compound is highly useful as such a liquid crystal compound. This carboxylic acid ester compound can be produced using a tetralin derivative.

[0010] Conventionally, as a general method for synthesizing a tetralin derivative, a naphthalene compound is converted to Raney nickel (R-Ni).
There has been known a method for reducing the catalyst with a catalyst. For example, 1
In 938, an example of reducing 1-naphthol in the presence of R-Ni was reported. In this method, 5-hydroxytetralin is obtained in a yield of 40% (J. Am, Chem. Soc., 60 , 664).
(1938)).

However, in this method, hydrogen is added to 350
There is a problem that the reaction needs to be performed under the high pressure condition of atm. Also, in such a reduction method using an R-Ni catalyst, it is difficult to selectively reduce one of the naphthalene rings forming the naphthalene compound, and therefore, two different types of naphthalene compounds having a substituent are required. A tetralin derivative is formed. Therefore, it has been difficult to selectively increase the yield of the tetralin derivative to be obtained by this method.

As another method, a method has been found in which an acetophenone derivative is used as a starting material to synthesize a tetralin derivative via a tetralone derivative obtained by a ring closure reaction (Helv. Chim. Acta., 65 , 1318 (1982)). ). According to this method, for example, when synthesizing 2-alkyl-6-phenyl-1,2,3,4-tetrahydronaphthalene, 4-phenylacetophenone is used as a starting material, and a tetralin derivative is obtained through a reaction process of actually six steps. However, there is a problem that it is difficult to synthesize efficiently.

As described above, according to the conventional method for synthesizing a tetralin derivative, it is difficult to synthesize a tetralin compound by selectively reducing a naphthalene compound, or a form in which one ring of a naphthalene compound is selectively reduced. In order to synthesize a tetralin derivative, it was necessary to perform synthesis through an extremely large number of reaction steps.

[0014]

SUMMARY OF THE INVENTION The present invention provides a highly useful tetralin derivative from a naphthalene compound with high efficiency.
Moreover, it is an object of the present invention to provide a novel method which can be manufactured with a high selectivity.

More specifically, an object of the present invention is to provide a method for efficiently producing a desired tetralin derivative by selectively reducing one ring of a naphthalene compound.

[0016]

According to the present invention, there is provided a method for producing a tetralin derivative, wherein one of the rings has a relatively electron-accepting substituent or atom and the other ring has a relatively electron-donating substituent. A naphthalene compound having a group or an atom is brought into contact with hydrogen in the presence of a Pd catalyst to selectively reduce a ring substituted with a substituent or an atom having a relatively high electron-donating property.

According to the method for producing a tetralin derivative of the present invention, by using a Pd catalyst as a catalyst, a group (or atom) having a high electron-donating property in a naphthalene ring is relatively compared with a substituent. Can be selectively reduced.

From this tetralin derivative, a carboxylate compound having high utility as a liquid crystal can be produced.

[0019]

DETAILED DESCRIPTION OF THE INVENTION Hereinafter, a method for producing a tetralin derivative according to the present invention will be specifically described. The method for producing a tetralin derivative of the present invention can be used, for example, in the step of producing a specific carboxylate compound having high utility as a liquid crystal compound, when synthesizing a tetralin derivative as a raw material from a naphthalene compound.

An example of the synthesis route of this carboxylic acid ester compound is as follows.

[0021]

Embedded image

In the method for producing a tetralin derivative of the present invention, 6-n-alkoxynaphthalene-2-carboxylic acid is applied under pressure with a palladium / carbon catalyst in the above exemplified synthetic route as shown below. It is shown as a step of obtaining 5,6,7,8-tetrahydro-6-n-alkoxynaphthalene-2-carboxylic acid by heating and hydrogenating.

[0023]

Embedded image

In the above example, the 6-n-alkoxynaphthalene-2-carboxylic acid used as a naphthalene compound is represented by a general formula. The naphthalene compound used as a raw material in the present invention is represented by the following formula [I]. Can be.

[0025]

Embedded image

... [I] In the above formula [I], R ^a is an electron donating group or atom, and R ^b is an electron accepting group or atom. M and n are each independently an integer of 0 to 4,
And has a relationship of m × n ≠ 0.

Here, examples of the electron donating group or atom represented by ^Ra include an alkyl group, an alkoxy group and a hydroxyl group. Examples of the electron-accepting property or atom represented by R ^b include a carboxyl group, a carbonyl, a nitro group, a halogen atom, and a cyano group. The electron-donating and electron-accepting properties of these groups or atoms are relative. For example, in the above formula [I], when comparing ^Ra and ^Rb , ^a group having a higher electron-accepting property is An electron-accepting group is a group having a lower electron-accepting property than the electron-accepting group. For example, given by the following equation [IA],

[0028]

Embedded image

When the alkoxy group represented by R—O— (R represents an alkyl group) and the carboxyl group represented by —COOH are compared, the alkoxy group has a higher electron donating property than the carboxyl group. In the compound represented by the formula [IA], the electron donating group (R ^a ) is an alkoxy group, and the electron accepting group (R ^b ) is a carboxyl group. Therefore, in the method of the present invention, the ring to which the alkoxy group as the electron donating group is bonded is selectively reduced.

The naphthalene compound is represented by the following formula [I-
As shown in B], when the compound has two or more substituents, the relative electron accepting property and electron donating property can be determined as follows.

[0031]

Embedded image

That is, a group R ¹ bonded to one ring,
The overall electron donating (or electron accepting) properties of R ² , R ³ and R ⁴ and the group R ⁵ ,
Compared with the total electron donating property (or electron accepting property) of R ⁶ , R ⁷ and R ⁸ , the ring having higher electron donating property has an electron donating group (or electron accepting group). And the other is a ring having an electron accepting group (or an electron donating group).

As described above, in the present invention, the electron-accepting group and the electron-donating group are relatively determined by comparing the two in a state of being bonded to the naphthalene ring.
As described above, even if the group is generally recognized as an electron-accepting group, as long as the group to be compared has a higher electron-accepting property, electron donation is limited in the compound. It is recognized as a sex group.

For example, a halogen atom and a carboxyl group have an electron donating halogen atom, a halogen atom and a cyano group have an electron donating halogen atom, and a halogen atom and a nitro group have an electron donating electron . In the carbonyl group and the cyano group, the carbonyl group is electron donating, in the carbonyl group and the nitro group, the carbonyl group is electron donating , and in the carboxyl group and the cyano group, the carboxyl group is electron donating . The carboxyl group of the carboxyl group and the cyano group has an electron donating property , and the ring to which the electron donating group is bonded is selectively reduced. These relative relationships also hold between groups and atoms.

In the present invention, the above naphthalene compound is brought into contact with hydrogen in the presence of a Pd catalyst. Although this catalyst can be used alone, it is preferable to use it by supporting it on a carrier. As the carrier used here, a substance usually used as a catalyst carrier can be used, but an alumina carrier, a carbon carrier, a silica carrier and the like are particularly preferably used. It is preferable that the specific surface area of these supports is as large as possible.
It has a specific surface area of about 00 m ² / g, preferably about 200 to 400 m ² / g.

The catalyst component Pd is supported on the carrier in an amount of usually 1 to 20% by weight, preferably 4 to 10% by weight. Particularly, in the present invention, a combination of Pd / carbon or a combination of Pd / alumina is preferable.

The amount of the catalyst as described above is usually 1 to 30% by weight, preferably 5 to 30% by weight, based on the naphthalene compound as the raw material.
It is used in the range of １５15% by weight. The reduction reaction of the naphthalene compound using the above catalyst is usually performed in a reaction solvent. The reaction solvent used here is a compound which has substantially no reactivity with naphthalene compounds, catalysts and hydrogen, and which is liquid near room temperature or a mixture of such compounds. Examples of such a solvent include a saturated hydrocarbon solvent, an ether solvent, an alcohol solvent, and a fatty acid solvent. Among them, ether solvents such as tetrahydrofuran, diethyl ether, dibutyl ether, dioxane and 2-methoxyethyl ether; alcohol solvents such as methanol, ethanol, propanol, 2-propanol and butanol; fatty acids such as acetic acid and propionic acid It is preferable to use a solvent. These solvents can be used alone or in combination of two or more. Among such reaction solvents, the catalyst Pd /
Considering compatibility with carbon, tetrahydrofuran, ethanol, acetic acid, and a mixed solvent of ethanol / acetic acid are preferably used. The reaction solvent is usually used in an amount of 1,000 to 20,000 parts by weight based on 100 parts by weight of the naphthalene compound.

In the reaction of the present invention using a Pd / carbon catalyst or a Pd / alumina catalyst, the reaction temperature is usually -20 to 2
The reaction is carried out at a temperature of 50 ° C, preferably 80 to 150 ° C. The reaction pressure at this time is not particularly limited, and is usually from normal pressure to 60 kg / cm ² · G, preferably from 10 to 30 kG.
g / cm ² · G, more preferably 15 to 25 kg / cm ² · G
Is set within the range of The reaction pressure is controlled by adjusting the pressure of hydrogen introduced into the reaction vessel. Under the above conditions, the reaction time is the reaction temperature,
It is appropriately set in consideration of the reaction pressure, the catalyst used, and the like, and is usually 5 minutes to 100 hours, preferably 1 to 20 hours.

By reacting in this manner, for example, in the naphthalene compound represented by the formula [I], the ring to which the electron-donating group (R ^a ) is bonded is selectively reduced to give the following formula [I]
I] is produced.

[0040]

Embedded image

[II] Here, R ^a , R ^b , m and n have the same meaning as in the formula [I]. Specifically, the naphthalene compound represented by the formula [IA] is obtained by selectively reducing the ring to which the electron-donating group -OR is bonded as represented by the following formula [II-A]. A tetralin derivative is formed.

[0042]

Embedded image

[II-A] According to the method for producing a tetralin derivative of the present invention as described above, one of the naphthalene rings is selectively reduced depending on the characteristics of the group bonded to the naphthalene compound. Can be efficiently synthesized. That is, according to the method of the present invention, a desired tetralin derivative can be synthesized from a naphthalene compound with a high selectivity, and the selectivity of this reaction is usually 20% or more, and 90% depending on the reaction conditions. A desired tetralin derivative can be synthesized with the above selectivity.

The tetralin derivative thus obtained can be separated from the reaction solution by using a known method such as recrystallization, column chromatography, and the like. The obtained tetralin derivative can be used for various applications. For example, a specific carboxylate compound having high utility as a liquid crystal material can be produced from the tetralin derivative according to the above reaction route.

Hereinafter, a method for producing a liquid crystal material from the tetralin derivative obtained by the method of the present invention will be described with reference to an example of a method for producing a carboxylic acid ester compound having high utility as a liquid crystal material.

In the above reaction route, 4-hydroxybenzoic acid ester and 4-benzyloxybenzoic acid are converted to 4-N, N-
The reaction between 4-hydroxybenzoic acid ester and 4- (4'-benzyloxybenzoyloxy) benzoic acid was carried out by using dimethylaminopyridine and methylene chloride as a solvent and reacting while dropwise adding an N, N'-dicyclohexylcarbodiimide solution. An ester compound can be obtained.

The ester compound obtained as described above is put into a solvent such as tetrahydrofuran and reduced with hydrogen gas in the presence of a reducing catalyst such as palladium / carbon to obtain a benzyl group from the ester compound. Can be obtained.

The benzyl group-eliminated ester compound obtained as described above and the ester compound obtained by the method of the present invention were obtained.
Using 5,6,7,8-tetrahydro-6-n-alkoxynaphthalene-2-carboxylic acid, 4-N, N-dimethylaminopyridine and methylene chloride as a solvent, a N, N′-dicyclohexylcarbodiimide solution is added dropwise. The carboxylic acid ester compound can be obtained by performing the reaction while performing the reaction. In addition,
Here, when the 4-hydroxybenzoic acid ester has an optically active group, the resulting carboxylate compound also has optical activity.

For example, the carboxylic acid ester compound obtained as described above can be represented by the following formula [A].

[0050]

Embedded image

... [A] In the above formula [A], R varies depending on the type of the substituent in the naphthalene compound used as a raw material in the method of the present invention, but is usually an alkyl group having 3 to 20 carbon atoms. ,
It is either an alkoxy group having 3 to 20 carbon atoms or a halogenated alkyl group having 3 to 20 carbon atoms.

In the above formula [A], R represents 3 to 2 carbon atoms.
When it is an alkyl group of 0, such an alkyl group may be any of a linear, branched, and alicyclic form, and R is a linear alkyl group. The carboxylic acid ester molecule has a rigid structure in which the molecule extends straight, and thus exhibits excellent liquid crystallinity.

Specific examples of such a linear alkyl group include hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, hexadecyl and octadecyl. be able to.

When R is a halogenated alkyl group having 3 to 20 carbon atoms, examples of the halogenated alkyl group include at least some of the atoms of the above-mentioned alkyl group as F, Cl, Br and And a group substituted with a halogen atom such as I.

When R is an alkoxy group having 3 to 20 carbon atoms, examples of such an alkoxy group include the above-mentioned alkoxy groups having an alkyl group. Specific examples of such an alkoxy group include a hexoxy group, a heptoxy group, an octyloxy group, a nonyloxy group, a decyloxy group, an undecyloxy group, a dodecyloxy group, a tetradecyloxy group, a heptadecyloxy group, and a hexadecyloxy group And an octadecyloxy group.

Among the compounds having R as described above, compounds having an alkoxy group show particularly excellent liquid crystallinity. In the above formula [A], X and Y are each independently, -COO -, - OCO -, - CH 2 CH 2 -, - C
_{H 2 O -, - OCH 2} -, - S-S -, - CO-CH 2 -
And it represents a group or a single bond selected from -CH ₂ -CO- the group consisting of.

When the carboxylic acid ester compound is used as a liquid crystal compound, X and Y each independently represent -COO-, -OCO-, -CH ₂ CH ₂
—, —CH ₂ O— and —OCH ₂ — are preferably selected. In particular, considering the linearity of the molecule, at least one of X and Y, and preferably both,
—COO— is preferred.

In the above formula [A], A and B
Are, independently of each other,

[0059]

Embedded image

Represents a group selected from the group consisting of Among these groups, when a carboxylic acid ester compound is used as a liquid crystal compound, in consideration of properties as a liquid crystal substance,

[0061]

Embedded image

The phenylene group is particularly preferred. In the formula [A], R
^* Represents 4 to 20 carbon atoms having at least one asymmetric carbon.
Represents an optically active group. The hydrogen atom bonded to the carbon atom constituting the optically active group is, for example, F, C
It may be substituted by a halogen atom such as l, Br and I, particularly preferably a fluorine atom.

Examples of such an optically active group are preferably-(CH ₂ ) ₃ -C ^* H (CH ₃ ) -C ₂ H ₅ , -CH ₂ -C
^{_{* H (CH 3) -C 2}} H 5, -C * H (CH 3) -C 6 H 13, -
_{^{C * H (CH 3) -C}} 5 H 11, -C * H (C 2 H 5) -C
^{_{6 H 13, -C * H (}} CF 3) -C 6 H 13, and -C ^* H (C
F ₃₎ may be mentioned chromatography CH ₂ over COO-C ₂ H _5.

Among these groups, when this carboxylic acid ester compound is used as a liquid crystal compound, the following groups are preferred in view of the properties as a liquid crystal substance. _{^{-C * H (CH 3) -C}} 6 H 13, -C * H (CF 3) -C 6 H 13
And -C ^* H (CF ₃₎ over CH ₂ over COO-C ₂ H ₅ further groups shown below Among these particularly preferred.

[0065] _{^{-C * H (CF 3) -C}} 6 H 13. In the formula [A], m and n each independently represent an integer of 0 to 2. However, in the above formula [A], both m and n do not become 0 at the same time.
In particular, when this carboxylic acid ester compound is used as a liquid crystal compound, m is preferably 1 or 2.

In the above formula [A], the 5,6,7,8-tetrahydronaphthyl group derived from the naphthalene compound by the method of the present invention includes 5,6,7,8-tetrahydro-1,5 -Naphthyl group 5,6,7,8-tetrahydro-1,6-naphthyl group 5,6,7,8-tetrahydro-2,6-naphthyl group and 5,6,7,8-tetrahydro-1,7- A naphthyl group can be mentioned.

In particular, when this carboxylic acid ester compound is used as a liquid crystal compound, it is preferable that the whole molecule be linear. Therefore, as the 5,6,7,8-tetrahydronaphthyl group, 5,6, The 7,8-tetrahydro-2,6-naphthyl group is particularly preferred.

Accordingly, the carboxylic acid ester compound represented by the above formula [A] is specifically represented by the following formula [A ']:

[0069]

Embedded image

... [A '] R, X, Y, m, n, A, B and R ^* are, for example, as shown in Tables 1 to 6 below, compound numbers [1] to [10]
4].

In the following table, R, X, Y, m, n,
A, B and R ^* have the same meanings as above, and p, q, r
Each of _{R: C p H q O r} - carbon atom number in the group, the number of hydrogen atoms, represents the number of oxygen atoms.

In the symbol A,

[0073]

Embedded image

, Respectively. Further, in the symbols R ^{*, _{b: -C * H (CF 3)}} -C 6 H 13 _{^{B: -C * H (CH 3)}} -C 6 H 13 C: -CH ₂ over C ^* H (CH ₃₎ -C ₂ H ₅ d: represents a _{^{-C * H (C 2 H 5}} ) -C 6 H 13. Hereinafter, the same applies in the present specification.

[0075]

[Table 1]

[0076]

[Table 2]

[0077]

[Table 3]

[0078]

[Table 4]

[0079]

[Table 5]

[0080]

[Table 6]

For example, 4- [4 '-(5 ",
6 ", 7", 8 "- tetrahydro -6"-n-decyloxy -2 "- naphthoyloxy) benzoyloxy] benzoic acid R-1 '' - figure ¹ H-NMR chart of trifluoromethyl heptyl ester It is shown in FIG. In the following formula, (eq) represents an equatorial conformation, and (ax) represents an axial conformation.

[0082]

Embedded image

In the above formula, numbers 1 to 16
Indicates a hydrogen atom, and this number indicates a peak in FIG.
It corresponds to the number attached to. Also, for example,
4- (5 ', 6', 7 ', 8'-tetrahydro-6'-n-decyloxy
-2'-Naphthoyloxy) benzoic acid R-1 "'-Trifluoromethy
Of ruheptyl ester ¹The H-NMR chart is shown in FIG.
Show.

[0084]

Embedded image

The numbers 1 to 15 in the above formula represent hydrogen atoms, and these numbers correspond to the numbers assigned to the peaks in FIG. The carboxylic acid ester compound represented by the formula [A] obtained as described above,
For example, it can be used as a liquid crystal compound.

Particularly, a carboxylic acid ester compound having optical activity can be used as a ferroelectric liquid crystal compound or an antiferroelectric liquid crystal compound. And among such carboxylic acid ester compounds, the following formulas [4] and [12]
The compound represented by represents particularly excellent liquid crystal properties.

[0087]

Embedded image

Table 7 shows the phase transition temperatures of the compounds represented by the formulas [4] and [12] which are particularly excellent as a liquid crystal compound. In the following table, Cry
The crystal phase, SmC _A ^* is an antiferroelectric phase, SmA is smectic A phase, Iso represents an isotropic liquid.

[0089]

[Table 7]

Among the carboxylic acid ester compounds represented by the formula [A], as exemplified in Table 7, many compounds exhibit a smectic phase in a wide temperature range. The liquid crystal compound has not only a wide temperature range in which a smectic phase is exhibited, but also an optical switching element manufactured using such a liquid crystal compound has excellent high-speed response.

This liquid crystal compound can be used alone, but can also be used as a liquid crystal composition by mixing with another liquid crystal compound. For example, this liquid crystal compound can be used as an auxiliary for a liquid crystal composition containing a compound exhibiting a chiral smectic phase as a main component.

When a display device or the like is formed using this liquid crystal compound, for example, in addition to the above-mentioned carboxylic acid ester compound and other liquid crystal compounds, furthermore, for example, an electric conductivity imparting agent and a life improving agent such as May be added to the liquid crystal compound.

The above liquid crystal compound can be used for a surface stabilized ferroelectric liquid crystal element, a surface stabilized antiferroelectric liquid crystal element, a helical distortion type element, a transient scattering type element, a guest-host type element, a vertical alignment liquid crystal element and the like. Can be used.

Among the above-mentioned liquid crystal compounds, liquid crystal compounds having ferroelectricity or antiferroelectricity may be used in addition to the above-mentioned applications, in addition to optical shutters, optical switching elements such as liquid crystal printers, piezoelectric elements and pyroelectric elements. It can be preferably used as a liquid crystal element such as an element.

[0095]

According to the method of the present invention, a tetralin derivative can be synthesized by selectively hydrogenating one ring of a naphthalene compound. Moreover, in this reaction, the ring to be reduced is specified by the type of the substituent of the naphthalene compound, the desired tetralin derivative can be synthesized with a very high selectivity, and the yield of this reaction itself is high.

Furthermore, this reaction does not change the reaction conditions, but the selectivity of the ring to be reduced depends on the substituent. Therefore, the reaction conditions can be easily set, and the desired tetralin derivative can be easily prepared. Can be synthesized. In addition, this reaction does not require a complicated reaction operation and is completed in one step, so that the reaction operation is easy.

By using the tetralin derivative obtained as described above, a carboxylate compound having high utility as a liquid crystal can be obtained.

[0098]

EXAMPLES Next, examples of the present invention will be described, but the present invention is not limited to these examples.

The R and S used below mean the R and S forms of the optical isomer.

[0100]

Example 1 4- [4 '-(5 ", 6", 7 ", 8" -tetrahydro-6 "-n-
Synthesis of decyloxy-2 "-naphthoyloxy) benzoyloxy] benzoic acid R-1"'-trifluoromethylheptyl ester.

First Step 5,6,7,8-Tetrahydro-6-n-decyloxynaphthalene-2-
Synthesis of carboxylic acids. In a 100 ml autoclave, 328 m of 6-n-decyloxynaphthalene-2-carboxylic acid was added.
g (1.0 mmol) and 5% palladium / carbon 0.1
g was mixed with 10 ml of tetrahydrofuran. Hydrogen was introduced into the autoclave, pressurized to 25 atm, and then
Stirred at C for 3 hours.

After the temperature was returned to normal temperature and normal pressure, the reaction mixture was filtered using Celite as a filter aid, and the obtained filtrate was concentrated.
Column purification using a 1: 1 mixed solvent of F) and n-hexane, and those obtained by recrystallization from n-hexane were added up to obtain a white solid of 5,6,7,8- Tetrahydro-6-n-
90 mg of decyloxynaphthalene-2-carboxylic acid (0.27
Mmol) (yield 27.0%, selectivity 95%).

[0103]

REFERENCE EXAMPLE 1 Second stage R-1-trifluoromethylheptanol 9.20 g (50 mmol), 4-benzyloxybenzoic acid 11.40 g (5
0 mmol), 4-N, N-dimethylaminopyridine 0.61
g (5 mmol) and 100 ml of methylene chloride in 11.33 g of N, N-dicyclohexylcarbodiimide.
(55 mmol) in 70 ml of methylene chloride solution were added dropwise at room temperature over 2.5 hours with stirring.

Further, the reaction was carried out at room temperature for 4 hours. The reaction mixture was filtered, and the obtained filtrate was concentrated. The concentrate was separated by column chromatography to obtain 15.96 g (40.6 mmol) of 4-benzyloxybenzoic acid R-1′-trifluoromethylhexyl ester as a white solid.

Third Step 15.96 g of R-1'-trifluoromethylhexyl ester of 4-benzyloxybenzoic acid obtained in the second step (40.6)
(Mmol), hydrogen was bubbled into a mixture of 1.6 g of 5% palladium / carbon and 80 g of tetrahydrofuran at room temperature and under normal pressure for 8 hours. The reaction mixture was filtered using celite as a filter aid, and the obtained filtrate was concentrated, and 12.34 g (40.6) of a white solid, 4-hydroxybenzoic acid R-1′-trifluoromethylhexyl ester, was obtained. Mmol).

Fourth stage 12.34 g (40.6 mmol) of R-1'-trifluoromethylhexyl ester of 4-hydroxybenzoic acid obtained in the third stage and 9.26 g (40.40 g) of 4-benzyloxybenzoic acid. 6
Mmol), 0.49 g of 4-N, N-dimethylaminopyridine
(4 mmol) and 80 ml of methylene chloride,
9.2 g (44.7) of N, N-dicyclohexylcarbodiimide
(Mmol) of methylene chloride was added dropwise over 2 hours at room temperature with stirring.

Further, the reaction was carried out at room temperature for 3.5 hours. The reaction mixture was filtered, and the obtained filtrate was concentrated. The concentrate was separated by column chromatography to obtain 19.64 g (38.2 mmol) of 4- (4'-benzyloxybenzoyloxy) benzoic acid R-1'-trifluoromethylhexyl ester as a white solid. I got

Step 5 19.64 g (38.2 mmol) of 4- (4'-benzyloxybenzoyloxy) benzoic acid R-1'-trifluoromethylhexyl ester obtained in step 4 and 5% palladium / Hydrogen was blown into a mixture of 3.0 g of carbon and 100 g of tetrahydrofuran at room temperature under stirring under normal pressure for 14 hours. The reaction mixture was filtered using celite as a filter aid, and the obtained filtrate was concentrated to give a white solid, 4-
16.29 g (38.2 mmol) of (4'-hydroxybenzoyloxy) benzoic acid R-1'-trifluoromethylhexyl ester were obtained.

Sixth Step The 5,6,7,8-tetrahydro-6 obtained in the first step of Example 1
-n-decyloxynaphthalene-2-carboxylic acid, 0.332
g (1.0 mmol), 0.424 g (1.0 mmol) of R-1'-trifluoromethylhexyl ester of 4- (4'-hydroxybenzoyloxy) benzoic acid obtained in the fifth step,
To a mixture of 0.012 g (0.1 mmol) of 4-N, N-dimethylaminopyridine and 25 ml of methylene chloride was added 10 ml of a methylene chloride solution containing 0.247 (1.2 mmol) of N, N'-dicyclohexylcarbodiimide at room temperature. The mixture was added dropwise over 2.5 hours with stirring. Further, the reaction was performed at room temperature for 2 hours. The reaction mixture was filtered, and the obtained filtrate was concentrated. The concentrate was separated by column chromatography to obtain 0.23 g of a white solid.

The value of the FD-mass spectrum of this white solid was M / e = 738. FIG. 1 shows the ¹ H-
3 shows a chart of an NMR spectrum. From the results of these analyses, this compound was found to be the desired 4- [4 '-(5 ", 6", 7 ", 8"
-Tetrahydro-6 "-n-decyloxy-2" -naphthoyloxy) benzoyloxy] benzoic acid R-1 "'-trifluoromethylheptyl ester.

[0111]

Example 2 Synthesis of 4- (5 ', 6', 7 ', 8'-tetrahydro-6'-n-decyloxy-2'-naphthoyloxy) benzoic acid R-1 "-trifluoromethylheptyl ester .

First Step 5,6,7,8-Tetrahydro-6-n-decyloxynaphthalene-2-
Synthesis of carboxylic acids. In a 1 liter autoclave, 50 g of 6-n-decyloxynaphthalene-2-carboxylic acid
(0.15 mol) and 5 g of 5% palladium / carbon were mixed in 500 ml of tetrahydrofuran. Hydrogen was introduced into this autoclave, pressurized to 20 atm, and then
Stirred for hours.

After returning to normal temperature and normal pressure, the reaction mixture was filtered using celite as a filter aid, and the obtained filtrate was concentrated. Then, a 1: 1 mixture of tetrahydrofuran (THF) and n-hexane was added. The column was purified using a solvent, and the total amount obtained by recrystallization from n-hexane was 5, 6, 7,
35.2 g of 8-tetrahydro-6-n-decyloxynaphthalene-2-carboxylic acid was obtained (yield 69%, selectivity 70%).

[0114]

REFERENCE EXAMPLE 2 5,6,7,8-Tetrahydro-6-n-decyloxynaphthalene-2-carboxylic acid obtained in the above Example 2 was added to 33
2 mg (1.0 mmol), 304 mg (1.0 mmol) of 4-hydroxybenzoic acid R-1′-trifluoromethylhexyl ester obtained in the third step of Example 1, 4-N, N-dimethylamino To a mixture of 12 mg (0.1 mmol) of pyridine and 25 ml of methylene chloride, 10 ml of a methylene chloride solution containing 247 mg (1.2 mmol) of N, N'-dicyclohexylcarbodiimide was added dropwise with stirring at room temperature over 2.5 hours. And reacted. The reaction mixture was filtered, and the obtained filtrate was concentrated. The concentrate was subjected to column purification using a 1: 1 mixed solution of dichloromethane and hexane to obtain a colorless transparent liquid 3.
00 mg was obtained.

The value of the FD-mass spectrum of this white solid was M / e = 618. FIG. 2 shows the ¹ H-
3 shows a chart of an NMR spectrum. From the results of these analyses, this compound was found to be the desired 4- (5 ', 6', 7 ', 8'-tetrahydro-6'-n-decyloxy-2'-naphthoyloxy) benzoic acid R-1 " -Trifluoromethylheptyl ester was identified.

[0116]

Example 3 4- (5 ', 6', 7 ', 8'-Tetrahydro-6'-n-decyloxy-2'-naphthoyloxy) benzoic acid R-1 "-trifluoromethylhepsyl ester Synthesis.

First Step 5,6,7,8-Tetrahydro-6-n-decyloxynaphthalene-2-
Synthesis of carboxylic acids.

In a 100 ml autoclave, 6-n-
328 mg (1 mmol) of decyloxynaphthalene-2-carboxylic acid and 0.1 g of 5% palladium / alumina;
10 ml of tetrahydrofuran (THF) was mixed. After introducing hydrogen into this autoclave and pressurizing to 30 atm,
The mixture was stirred at 140 ° C. for 5 hours.

After the temperature was returned to normal temperature and normal pressure, the reaction mixture was filtered using Celite as a filter aid. The obtained filtrate was concentrated, and then a 1: 1 mixture of tetrahydrofuran (THF) and n-hexane was added. The residue was purified by column using a solvent, and the residue obtained by recrystallization from n-hexane was added to obtain 3,12 mg of desired 5,6,7,8-tetrahydro-6-n-decyloxy-2-carboxylic acid. (Yield 94.1%, selectivity 95)
%).

[0120]

Reference Example 2 Second Step 332 mg (1.0 mmol) of 5,6,7,8-tetrahydro-6-n-decyloxy-2-carboxylic acid obtained in the same manner as in Example 3 above was used as a reference. 4-hydroxybenzoic acid R-1'-trifluoromethylhexyl ester 304 mg (1.0 mmol) 4-N, N-dimethylaminopyridine 12 mg and methylene chloride 25 ml obtained in the third step of Reference Example 1 according to Example 2
Is mixed with N, N'-dicyclohexylcarbodiimide 2
10m of methylene chloride solution containing 47mg (1.2mmol)
l was added dropwise over 2.5 hours with stirring at room temperature to react.

The reaction mixture was filtered, and the obtained filtrate was concentrated. The filtrate was purified by column using a 1: 1 mixed solution of dichloromethane and hexane to obtain 300 mg of a colorless liquid. Since the result of instrumental analysis of this compound was consistent with the result obtained in Reference Example 2, this compound was identified as 4- (5 ', 6', 7 ', 8'-tetrahydro-6'-n-decyloxy-2' -Naphthoyloxy)
It was identified as benzoic acid R-1 "-trifluoromethylhepsyl ester.

[Brief description of the drawings]

FIG. 1 shows the results of 4- [4 '-(5 ", 6", 7 ", 8" -tetrahydro-
¹ is a chart of 1H-NMR spectrum of 6 "-n-decyloxy-2" -naphthoyloxy) benzoyloxy] benzoic acid R-1 "'-trifluoromethylheptyl ester.

FIG. 2 shows 4- (5 ′, 6 ′, 7 ′, 8′-tetrahydro-6′-n-
1 is a chart of ¹ H-NMR spectrum of decyloxy-2′-naphthoyloxy) benzoic acid R-1 ″ -trifluoromethylheptyl ester.

Continued on the front page (72) Inventor Shinichi Nishiyama 580-32 Takuji, Nagaura, Sodegaura-cho, Kimitsu-gun, Chiba Prefecture Inside Mitsui Petrochemical Industries Co., Ltd. Takuji No. 580 No. 32 Inside Mitsui Petrochemical Industry Co., Ltd. (56) References JP-A-63-83033 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) C07B 35/02 C07C 67/303 C07C 69/76

Claims (3)

(57) [Claims] 1. A naphthalene compound having a relatively electron-accepting substituent or atom on one ring and a relatively electron-donating substituent or atom on the other ring in the presence of a Pd catalyst. To produce a tetralin derivative by contacting with a hydrogen to selectively reduce a ring substituted with a substituent or atom having a relatively high electron donating property. 2. The method for producing a tetralin derivative according to claim 1, wherein the catalyst is supported on a carrier. 3. The relatively electron-accepting substituent is a group selected from the group consisting of a carboxyl group, a carbonyl, a nitro group, a halogen atom and a cyano group, and the relatively electron-donating substituent is 2. The method for producing a tetralin derivative according to claim 1, wherein the group is selected from the group consisting of an alkyl group, an alkoxy group and a hydroxyl group.