JP2009067753A - Method for producing diarylmethane compound or cyclic organic compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a diarylmethane compound in high yield while reducing the load on the environment. <P>SOLUTION: The diarylmethane compound is produced by the dehydration reaction of (A) an aromatic compound expressed e.g. by general formula (A1) with (B) a benzyl alcohol which may have substituents in the presence of crystalline molybdenum trioxide. In the formula (A1), R<SB>1</SB>is a substituent consisting of a 1-4C alkyl group or a 1-4C alkoxyl group; x is the number of the R<SB>1</SB>group and is an integer of 0-5; when x is 2 to 5, the multiple R<SB>1</SB>groups may be different from each other. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for producing a diarylmethane compound or a cyclic organic compound.

  Diarylmethane compounds typified by diphenylmethane and cyclic organic compounds typified by 9,10-dihydroanthracene are useful as raw materials for pharmaceuticals and chemical products. In general, these compounds can be synthesized by eliminating a hydroxyl group of benzyl alcohol and hydrogen of an aromatic compound. That is, it can be synthesized by dehydrating benzyl alcohol and an aromatic compound.

For example, Non-Patent Document 1 discloses a method of obtaining diphenylmethane by reacting benzyl alcohol and benzene in the presence of sulfuric acid and aluminum chloride. Non-Patent Document 2 discloses a method of obtaining a diarylmethane compound by reacting benzyl alcohol and an aromatic compound in the presence of zeolite as a solid acid catalyst.
Further, Non-Patent Document 3 discloses a method for obtaining a diarylmethane compound by reacting benzyl alcohol with an aromatic compound in the presence of Nafion (registered trademark), which is a copolymer of perfluorosulfonic acid and tetrafluoroethylene. Has been.

  However, the methods disclosed in these documents have poor reaction activity and reaction selectivity, and it has been difficult to obtain a diarylmethane compound in a high yield. Furthermore, since the method disclosed in Non-Patent Document 1 requires the use of a strong acid, there is a problem that it is inferior in environmental compatibility.

From the above, a method for obtaining a diarylmethane compound or a cyclic organic compound that has a high yield and a low environmental burden has been desired.
G. A Olah, Freidel-Crafts and Related reactions, Vol II, NewYork, John Wile & Sons Inc. New York, (1964) Rao, YX; Trudeau, M .; Antonelli, DJ Am. Chem. Soc., 128,13996, (2006) Yamato, T .; Hideshima, C .; Prakash, GKS; Olah, GAJ Org. Chem., 56, 2089 (1991)

  In view of the above, the present invention provides a high yield and low environmental load, such as a diarylmethane compound or a cyclic organic compound such as 9,10-dihydroanthracene (hereinafter also simply referred to as “cyclic organic compound”). ) Is provided.

［式（Ａ１）中、Ｒ_１は置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である；
ｘは前記Ｒ_１の数であり、０〜５の整数である；
ｘが２〜５である場合、それぞれのＲ_１は異なっていてもよい］

［式（Ａ２）中、Ｒ_２はナフタレン環の１〜８位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である；
ｙは前記Ｒ_２の数であり、０〜７の整数である；
ｙが２〜７である場合、それぞれのＲ_２は異なっていてもよい］
［２］ （Ｄ）一般式（Ｄ１）で表されるアルコールを、結晶性の三酸化モリブデンの存在下で分子内脱水反応させる、一般式（Ｅ）で表される環式有機化合物の製造方法。

［式（Ｄ１）中、数字は位置番号である；
Ｒ_３は３’〜６’位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である；
ｐは前記Ｒ_３の数であり、０〜４の整数である；ｐが２〜４である場合、それぞれのＲ_３は異なっていてもよい；
Ｒ_４は３〜６位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である；
ｑは前記Ｒ_４の数であり、０〜４の整数である；ｑが２〜４である場合、それぞれのＲ_４は異なっていてもよい；
ｎは１または２である］

［式（Ｅ）中、数字は位置番号である；
Ｒ_３は５〜８位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である；
ｐは前記Ｒ_３の数であり、０〜４の整数である；ｐが２〜４である場合、それぞれのＲ_３は異なっていてもよい；
Ｒ_４は１〜４位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である；
ｑは前記Ｒ_４の数であり、０〜４の整数である；ｑが２〜４である場合、それぞれのＲ_４は異なっていてもよい；
ｎは１または２である］
［１］に記載の製造方法。
［３］ 前記結晶性の三酸化モリブデンは、板状であり、電界放射型走査電子顕微鏡を用いて測定された板状粒子の平均サイズが、縦０．５〜２μｍ、横１〜３μｍ、厚さ３０〜２００ｎｍである、［１］または［２］に記載の製造方法。
［４］前記結晶性の三酸化モリブデンの全表面積中に占める板状面の面積の割合が、６０〜９５％である、［１］〜［３］のいずれかに記載の製造方法。
［５］前記結晶性の三酸化モリブデンの板状面の面積が、５〜２０ｍ^２／ｇである、［１］〜［４］いずれかに記載の製造方法。 As a result of intensive studies, the inventors have found that the above problem can be solved by using crystalline molybdenum trioxide. That is, the said subject is solved by the following this invention.
[1] (A) an aromatic compound represented by the general formula (A1) or (A2);
(B) benzyl alcohol which may have a substituent, or naphthalenemethanol which may have a substituent,
A method for producing a diarylmethane compound, wherein a dehydration reaction is performed in the presence of crystalline molybdenum trioxide.

[In Formula (A1), R ₁ is a substituent, which is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
x is the number of R ₁ and is an integer of 0 to 5;
when x is 2-5, each R ₁ may be different]

[In the formula (A2), R ₂ is a substituent at the 1 to 8 position of the naphthalene ring and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
y is the number of R ₂ and an integer of 0 to 7;
when y is 2-7, each R ₂ may be different]
[2] (D) A process for producing a cyclic organic compound represented by the general formula (E), wherein the alcohol represented by the general formula (D1) is subjected to an intramolecular dehydration reaction in the presence of crystalline molybdenum trioxide. .

[In the formula (D1), the number is a position number;
R ₃ is a substituent at the ₃ ′ to 6 ′ position and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
p is the number of R ₃ and is an integer of 0 to 4; when p is 2 to 4, each R ₃ may be different;
R ₄ is a substituent at the 3-6 position, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
q is the number of R ₄ and is an integer of 0 to 4; when q is 2 to 4, each R ₄ may be different;
n is 1 or 2]

[In the formula (E), the number is a position number;
R ₃ is a substituent at the 5- to 8-position, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
p is the number of R ₃ and is an integer of 0 to 4; when p is 2 to 4, each R ₃ may be different;
R ₄ is a substituent at the 1 to 4 position and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
q is the number of R ₄ and is an integer of 0 to 4; when q is 2 to 4, each R ₄ may be different;
n is 1 or 2]
[1] The production method according to [1].
[3] The crystalline molybdenum trioxide is plate-like, and the average size of the plate-like particles measured using a field emission scanning electron microscope is 0.5 to 2 μm in length, 1 to 3 μm in width, and thickness. The production method according to [1] or [2], wherein the thickness is 30 to 200 nm.
[4] The production method according to any one of [1] to [3], wherein the ratio of the area of the plate-like surface in the total surface area of the crystalline molybdenum trioxide is 60 to 95%.
[5] The manufacturing method according to any one of [1] to [4], wherein an area of the plate-like surface of the crystalline molybdenum trioxide is 5 to ²⁰ m ² / g.

  According to the present invention, a diarylmethane compound or a cyclic organic compound can be obtained with high yield under conditions with reduced environmental load. That is, a method for producing a diarylmethane compound or a cyclic organic compound that is excellent in safety and productivity can be provided.

  In the following, a method for producing a diarylmethane compound and a method for producing a cyclic organic compound will be described separately. In the presence of crystalline molybdenum trioxide, both are described as “hydroxyl group of hydroxymethyl group bonded to an aromatic ring”. And desorbing hydrogen on the aromatic ring.

1. Method for producing diarylmethane compound The method for producing a diarylmethane compound of the present invention comprises:
(A) an aromatic compound represented by the general formula (A1) or (A2);
(B) benzyl alcohol which may have a substituent, or naphthalenemethanol which may have a substituent,
The dehydration reaction is performed in the presence of crystalline molybdenum trioxide.
A diarylmethane compound is a compound in which two hydrogens of methane are each substituted with an aromatic compound.

上記反応式は、一般式（Ａ１）で表される化合物と、ベンジルアルコール（式（Ｂ１））を原料として用いた場合の反応スキームである。この場合、ジアリールメタン化合物は式（Ｃ１）で表される化合物となる。ベンジルアルコールは、置換基を有していてもよい。 The reaction formula of the present invention is shown below.

The above reaction formula is a reaction scheme in the case where a compound represented by the general formula (A1) and benzyl alcohol (formula (B1)) are used as raw materials. In this case, the diarylmethane compound is a compound represented by the formula (C1). Benzyl alcohol may have a substituent.

  In the case of using the compound represented by the general formula (A2) and the benzyl alcohol optionally having a substituent as a raw material in addition to the combination of the above raw materials, the above reaction is represented by the general formula (A2). In the case where the starting material is a naphthalene methanol which may have a substituent and a substituent; the case where the compound represented by the general formula (A1) and a naphthalene methanol which may have a substituent are used as a starting material. is there.

(1) About (A) component In this invention, the aromatic compound represented by general formula (A1) or (A2) is used as (A) component of a raw material. The compound represented by the general formula (A1) is benzene or benzene having a substituent. However, since hydrogen to be eliminated is required in the dehydration reaction, the maximum number of substituents of benzene having a substituent is five. The compound represented by the above formula (A1) is also referred to as “benzenes”.

式（Ａ１）中、Ｒ_１は置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である。
ｘは前記Ｒ_１の数であり、０〜５の整数である。ｘが２〜５である場合、それぞれのＲ_１は異なっていてもよい。

In formula (A1), R ₁ is a substituent, which is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms.
x is the number of R ₁ and is an integer of 0 to 5. When x is 2 to 5, each R ₁ may be different.

  Specific examples of benzenes include benzene; toluene, p-xylene, o-xylene, mesitylene (trimethylbenzene), alkylbenzene such as ethylbenzene, diethylbenzene, propylbenzene, and butylbenzene; alkoxybenzene such as anisole (methoxybenzene) It is.

  When a structurally target compound such as benzene, p-xylene, or mesitylene is used as the benzene, a diarylmethane compound having no isomer can be obtained.

  In addition, when a compound having an electron-donating methoxy group as a substituent, such as anisole, is used as the benzene, only diarylmethane compounds in which a methylene group is bonded to the para- or ortho-position with respect to the methoxy group of anisole. Is selectively obtained. That is, a compound having a methylene group bonded to the meta position cannot be obtained. As will be described later, anisole is subjected to an electrophilic substitution reaction by benzyl alcohol-derived benzyl cation or naphthalenemethanol-derived naphthylmethyl cation (hereinafter, benzyl cation and naphthylmethyl cation are collectively referred to as “benzyl cation”). Inferred to receive. When anisole undergoes an electrophilic substitution reaction, it has a remarkable ortho- and para-orientation, so that an electrophilic substitution reaction at the meta position hardly occurs, and a diarylmethane compound in which a methylene group is bonded to the meta position of anisole is obtained. It is not considered.

  Similarly, when toluene is used as the benzene, a diarylmethane compound in which a methylene group is bonded to the para or ortho position with respect to the methyl group of toluene is easily obtained. Toluene is not as electron-donating as anisole, but has a methyl group which is an electron-donating group, so it is presumed that a compound having a methylene group bonded to the meta position is difficult to obtain.

  The compound represented by the general formula (A2) is naphthalene or naphthalene having a substituent. However, since hydrogen to be eliminated is necessary in the dehydration reaction described later, the maximum number of substituents of naphthalene having a substituent is seven. The compound represented by the general formula (A2) is also referred to as “naphthalenes”.

式（Ａ２）中、Ｒ_２はナフタレン環の１〜８位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である。
ｙは前記Ｒ_２の数であり、０〜７の整数である。ｙが２〜７である場合、それぞれのＲ_２は異なっていてもよい。

In formula (A2), R ₂ is a substituent at the 1 to 8 position of the naphthalene ring, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms.
y is the number of the _{R 2,} it is an integer of 0-7. When y is 2-7, each R ₂ may be different.

  Specific examples of naphthalenes include naphthalene; 1-methylnaphthalene, 2-methylnaphthalene, 2,6-dimethylnaphthalene, 1-ethylnaphthalene, 2-ethylnaphthalene, 1-propylnaphthalene, 2-propylnaphthalene, 1-butyl. Alkylnaphthalene such as naphthalene and 2-butylnaphthalene; alkoxynaphthalene such as 1-methoxynaphthalene and 2-methoxynaphthalene.

  As the alkylnaphthalene, a compound having no substituent at the 1-position is preferable. As will be described later, in the reaction of the present invention, the naphthalene ring is electrophilically substituted with a benzyl cation or the like. The reactivity of the reaction depends on the stability of the intermediate carbocation generated by the electrophilic substitution reaction. It is known that an intermediate carbocation generated by attacking the 1-position of the naphthalene ring is more stable than an intermediate carbocation generated by attacking the 2-position of the naphthalene ring. Accordingly, the alkylnaphthalene preferably has no substituent at the 1-position.

In the alkoxynaphthalene, either the 1-position or the 2-position may be substituted. Since the alkoxyl group has an electron donating property, when it is bonded to the 1-position of naphthalene, a diarylmethane compound in which a methylene group is bonded to the 4-position of naphthalene is easily obtained. When the alkoxyl group is substituted at the 2-position of naphthalene, a diarylmethane compound having a methylene group bonded at the 1-position is easily obtained.
The above benzenes and naphthalenes may be collectively referred to as “benzenes”.

(2) About (B) component In this invention, the benzyl alcohol or naphthalene methanol which may have a substituent is used as (B) component of a raw material. The “benzyl alcohol optionally having a substituent (also referred to as“ benzyl alcohol ””) refers to benzyl alcohol or benzyl alcohol having a substituent on the benzene ring. The substituent is preferably an alkyl group or an alkoxyl group.
Examples of benzyl alcohols include benzyl alcohol, (methoxyphenyl) methanol, (3,4-dimethoxyphenyl) methanol, (4-isopropylphenyl) methanol (also referred to as “cuminol”).

  The “optionally substituted naphthalene methanol (also referred to as“ naphthalene methanol ”)” refers to naphthalene methanol or naphthalene methanol having a substituent on the naphthalene ring. Naphthalenemethanol is a compound represented by the following formula (B2).

  In formula (B2), the hydroxymethyl group may be bonded to the 1-position or 2-position of naphthalene, but is preferably bonded to the 1-position. In the present invention, it is considered that a diarylmethane compound is obtained by an electrophilic substitution reaction of naphthylmethyl cation with benzene. The 1-naphthylmethyl cation is more stable than the 2-naphthylmethyl cation. Therefore, when 1-naphthol which generates 1-naphthylmethyl cation is used as naphthalenemethanol, the reactivity can be increased.

When the naphthalene ring has a substituent, the substituent is preferably an alkyl group or an alkoxyl group.
The above benzyl alcohols and naphthalenemethanols may be collectively referred to as “benzyl alcohols”.

  The ratio of benzenes and benzyl alcohols is not particularly limited as long as it is a chemical equivalent. However, it is preferable that benzyl alcohol etc. is 1 mol or more with respect to 1 mol of benzene etc., It is more preferable that it is 10-200 mol, It is more preferable that it is 30-90 mol. This is because the reaction can be performed efficiently.

(3) About molybdenum trioxide Molybdenum trioxide is a compound represented by MoO ₃ . Molybdenum trioxide is known to be amorphous and crystalline. In the present invention, crystalline molybdenum trioxide (hereinafter simply referred to as “molybdenum trioxide”) is used. Molybdenum trioxide is an orthorhombic crystal and has a layered structure in which the two vertices of the distorted octahedron of MoO ₆ are shared. The layer has a thickness of about 30 to 60 nm.

In the present invention, molybdenum trioxide acts as a catalyst when synthesizing a diarylmethane compound. The mechanism is presumed as follows. A case where benzyl alcohol is used as the A component will be described as an example.
Molybdenum trioxide may generate Mo sites that are unstable in terms of valence due to elimination of oxygen atoms. The part is in a state where electrons are insufficient. The site then behaves like a Lewis acid and pulls out the hydroxyl group of benzyl alcohol. As a result, a benzyl cation is generated. The benzyl cation is subjected to nucleophilic attack by the aforementioned benzenes and the like. Conversely, the benzyl cation makes an electrophilic attack on benzenes and the like. If molybdenum trioxide has a high proton donating ability like Bronsted acid, it is considered that dibenzyl ether is generated by donating a proton to benzyl alcohol, but in the present invention, dibenzyl ether is not generated. From this, it is speculated that molybdenum trioxide plays a role of Lewis acid, thereby generating a benzyl cation.

  The Lewis acid site is likely to occur on the surface of molybdenum trioxide. Therefore, molybdenum trioxide preferably has a large surface area, that is, preferably has a small particle size. Further, it is considered that the Lewis acid site is most likely to occur on the 010 plane according to the Miller index of molybdenum trioxide having a layered structure. For this reason, it is preferable that molybdenum trioxide is plate-shaped. From the above, the molybdenum trioxide of the present invention is plate-like, and the average size of the plate-like particles is preferably 0.5 to 2 μm in length, 1 to 3 μm in width, and 30 to 200 nm in thickness. The size of the plate-like particle is preferably measured from the obtained image using a field emission scanning electron microscope or the like.

  Furthermore, in the molybdenum trioxide of the present invention, the ratio of the area of the plate-like surface to the total surface area (also referred to as “R value”) is preferably 60 to 95%. The R value can be obtained by image analysis from an image of a field emission scanning electron microscope. This is because when the R value is within the above range, the above-described Lewis acid site is likely to occur. The plate-like surface is the 010 surface in the Miller index.

The molybdenum trioxide of the present invention more preferably has a plate-like surface area (also referred to as “A value”) of 5 to ²⁰ m ² / g. The A value can be obtained by image analysis from an image of a field emission scanning electron microscope. This is because when the A value is within the above range, the above-described Lewis acid site is likely to occur.

The molybdenum trioxide of the present invention may be obtained by preparing a commercially available product and pulverizing it into a desired shape. However, as shown below, the chemical formula (NH ₄ ) ₆ Mo ₇ O ₂₄ · 4H It is preferable to synthesize ammonium heptamolybdate tetrahydrate (hereinafter also referred to as “AHM”) represented by ₂ O.

  First, the molybdenum trioxide of the present invention may be obtained by firing AHM in an air atmosphere or a nitrogen atmosphere. Specifically, firing can be performed by placing AHM in a crucible and heating at 400 ° C. for a fixed time. The time maintained at 400 ° C. is preferably 1 to 5 hours, more preferably about 2 hours. Moreover, it is preferable that the temperature increase rate at the time of heating to 400 degreeC is about 10 degreeC / min.

  As the atmosphere for firing, molybdenum trioxide obtained as an air atmosphere is referred to as “MCA”, and molybdenum trioxide obtained as a nitrogen atmosphere is referred to as “MCN”. The molybdenum trioxide of the present invention is preferably MCN. This is because the already described R and A values can be made larger than MCA, and excellent catalytic activity is exhibited.

The molybdenum trioxide of the present invention may be obtained by baking ammonium heptamolybdate tetrahydrate (AHM) after washing with water or a solvent to remove impurities such as salt and organic matter. Such a method of extracting impurities from AHM with a solvent or the like to obtain molybdenum trioxide may be referred to as a “solvent extraction method”. Firing is preferably performed in an air atmosphere. Molybdenum trioxide obtained by baking AHM after extracting impurities with a solvent in an air atmosphere is referred to as “MSEA”.
Further, it is not preferable to sinter AHM after extracting impurities with a solvent in a nitrogen atmosphere because Mo ₄ O ₁₁ is obtained instead of molybdenum trioxide. Although this mechanism is not clear, it is guessed as follows.

The AHM from which impurities have been removed tends to desorb oxygen atoms from the AHM when fired for some reason. Therefore, the valence of the generated molybdenum trioxide tends to be lower than hexavalent where it should originally be hexavalent. However, when fired in an air atmosphere, oxygen is abundant in the atmosphere, and desorbed oxygen atoms are supplied from the atmosphere, so that the valence of molybdenum does not change. On the other hand, when firing in a nitrogen atmosphere, since there is no oxygen supply source, oxygen is easily desorbed from the AHM, and the valence of molybdenum decreases. As a result, a compound containing Mo ₄ O ₁₁ as a main component is obtained. Since the compound does not have a layered structure like molybdenum trioxide, it is considered that the compound does not function as a catalyst in the present invention.

The solvent extraction method is preferably performed as follows.
1) Prepare a beaker containing pure water, insert AHM into it, and stir.
2) Subsequently, an organic solvent is inserted into the beaker and stirred.
3) Filter to obtain AHM from which impurities have been removed.
4) AHM is fired by the method already described.
The amount of pure water used in the step 1) is not particularly limited, but is preferably 50 to 100 parts by mass with respect to 1 part by mass of AHM. The type of the organic solvent used in the step 2) is not particularly limited, but examples of preferable solvents include acetone and pentane. The amount of the organic solvent is preferably 50 to 200 parts by mass with respect to 1 part by mass of AHM.

The molybdenum trioxide of the present invention is particularly preferably MSEA. This is because MSEA has a higher R value and A value than the aforementioned MCN and MCN, and has excellent performance as a catalyst of the present invention.
The reason why MSEA has higher R and A values than MCN and MCN is presumed to be because it is fired in a state in which impurities are removed, and the resulting fired product becomes highly pure molybdenum trioxide. The This is because molybdenum trioxide inherently has a layered structure and thus has a high R value and A value.

  The molybdenum trioxide thus obtained may be treated with alkoxysilane or the like as necessary. The treatment with alkoxysilane may be performed by a known method. As an example of the method, MCN or the like can be immersed in a toluene solution containing alkoxysilane and reacted for a while under toluene reflux. When molybdenum trioxide treated with alkoxysilane is used in the reaction of the present invention, an effect of enhancing the reactivity can be expected by improving affinity with a solvent, a raw material or the like.

The amount of molybdenum trioxide used is not particularly limited as long as the reaction proceeds sufficiently, but is preferably about 1 to 1.5 g with respect to 1 mL of benzyl alcohol.
Since molybdenum trioxide used in the present invention is a heterogeneous catalyst, it can be easily recovered by filtration or the like after the reaction. Furthermore, molybdenum trioxide can be reused, and has an advantage that the environmental load is small.

(4) Solvent In the present invention, since benzyl alcohols are liquid, the reaction may be performed without using a solvent, but a solvent may be used. Although a well-known thing may be used for a solvent, A 1, 4- dioxane and nitromethane are contained in the example of a preferable solvent.

(5) Reaction conditions The reaction of the present invention may be carried out under arbitrary conditions, but a preferable reaction method will be described below.
Raw materials such as benzyl alcohol and benzene, molybdenum trioxide and, if necessary, a solvent are charged into a glass container. The glass container is heated in an oil bath or the like so as to be sealed in an argon gas atmosphere. At that time, it is preferable to stir the system using a magnetic stirrer or the like.
The reaction temperature is preferably set so that the benzene or solvent is refluxed. The reaction time is appropriately adjusted depending on the progress of the reaction. After completion of the reaction, molybdenum trioxide is separated by filtration. The target compound remaining in the filtrate is isolated by a conventional method.

2. Manufacturing method of cyclic organic compound The manufacturing method of the cyclic organic compound represented by the general formula (E) of the present invention includes:
(D) The alcohol represented by the general formula (D1) is subjected to an intramolecular dehydration reaction in the presence of crystalline molybdenum trioxide.
The cyclic organic compound represented by the general formula (E) has a structure in which two benzene rings are bonded by an alkyl chain.

式（Ｅ）中、Ｒ_３は５〜８位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である。
ｐは前記Ｒ_３の数であり、０〜４の整数である。ｐが２〜４である場合、それぞれのＲ_３は異なっていてもよい。
Ｒ_４は１〜４位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である。
ｑは前記Ｒ_４の数であり、０〜４の整数である。ｑが２〜４である場合、それぞれのＲ_４は異なっていてもよい。
ｎは１または２である。

In formula (E), R ₃ is a substituent at the 5 to 8 position, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms.
p is the number of R ₃ and an integer of 0-4. When p is 2 to 4, each R ₃ may be different.
R ₄ is a 1 to 4 position substituent, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms.
q is the number of R ₄ and is an integer of 0 to 4. When q is 2-4, each R ₄ may be different.
n is 1 or 2.

  Examples of the compound represented by the general formula (E) include 9,10-dihydroatracene and 10,11-dihydro-5H-dibenzo [a, d] cycloheptene.

(1) About (D) component In this invention, the alcohol represented by general formula (D1) which is (D) component is used as a raw material. The alcohol represented by the general formula (D1) is an alcohol in which one hydrogen of methanol is substituted with a phenyl group. However, a phenylalkyl group is bonded to the 2-position of the phenyl group.
The alcohol represented by the general formula (D1) may be hereinafter referred to as “specific alcohol”.

式（Ｄ１）中、数字は位置番号を示す。Ｒ_３はフェニルアルキル基上の置換基であり、２’位以外、すなわち３’〜６’位の置換基である。２’位は、分子内脱水反応に必要であるため、置換されていない。Ｒ_３は炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である。Ｒ_３が３’位に結合していると立体障害により分子内脱水反応が進みにくくなるおそれがあるため、Ｒ_３は３’位に結合していないことが好ましい。ｐは前記Ｒ_３の数であり、０〜４の整数である。ｐが２〜４である場合、それぞれのＲ_３は異なっていてもよい。
Ｒ_４は３〜６位の置換基であり、炭素数が１〜４のアルキル基、または炭素数が１〜４のアルコキシル基である。ｑは前記Ｒ_４の数であり、０〜４の整数である。ｑが２〜４である場合、それぞれのＲ_４は異なっていてもよい。ｎは１または２である。

In the formula (D1), numerals indicate position numbers. R ₃ is a substituent on the phenylalkyl group, and is a substituent other than the 2 ′ position, that is, the 3 ′ to 6 ′ position. The 2 ′ position is not substituted because it is necessary for the intramolecular dehydration reaction. R ₃ is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms. If R ₃ is bonded to the 3 ′ position, the intramolecular dehydration reaction may be difficult to proceed due to steric hindrance, and therefore R ₃ is preferably not bonded to the 3 ′ position. p is the number of R ₃ and an integer of 0-4. When p is 2 to 4, each R ₃ may be different.
R ₄ is a substituent at the 3-6 position, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms. q is the number of R ₄ and is an integer of 0 to 4. When q is 2-4, each R ₄ may be different. n is 1 or 2.

  Examples of preferred compounds of the specific alcohol include (2-benzylphenyl) methanol and (2-phenylethylphenyl) methanol.

(2) About molybdenum trioxide Molybdenum trioxide may be the same as described in the method for producing a diarylmethane compound. However, the amount of molybdenum trioxide used is preferably about 5 to 8 g with respect to 1 mol of the specific alcohol.

(3) Solvent Since the specific alcohol is solid at room temperature, it is preferable to use a solvent. It is preferable to use the same solvent as described in the method for producing a diarylmethane compound. Although the quantity of a solvent is not specifically limited, It is preferable that it is about 0.1-0.3L with respect to 1 mol of specific alcohols.

(4) Reaction conditions The reaction conditions are preferably as described in the method for producing a diarylmethane compound.

In the examples, all reagents manufactured by Wako Pure Chemical Industries, Ltd. were used.
[Synthesis Example 1: Synthesis of MCA]
A crucible was charged with 15 g of ammonium heptamolybdate tetrahydrate (AHM) represented by the chemical formula (NH ₄ ) ₆ Mo ₇ O ₂₄ · 4H ₂ O. The crucible was placed in an oven, heated to 400 ° C. at a heating rate of 10 ° C./min under an air stream of 50 mL / min, and calcined by holding at 400 ° C. for 2 hours. Next, the crucible was allowed to cool in an oven and cooled to 50 ° C. or lower. The MCA thus obtained was stored in a sealed container.

The MCA thus obtained was subjected to X-ray diffraction analysis using RINT Ultimate + from Rigaku Corporation, and confirmed to be molybdenum trioxide.
The average size of the plate-like particles of MCA particles observed using a field emission scanning electron microscope was 1 μm in length, 1.5 μm in width, and 60-100 nm in thickness.
The surface area was measured by the BET method using the MCA field emission scanning electron microscope (manufactured by JEOL Ltd., JSM-7400F), the R value and the A value, and 6AG manufactured by Quant Chrome Instruments. The respective values are shown in Table 1.

[Synthesis Example 2: Synthesis of MCN]
MCN was obtained in the same manner as in Synthesis Example 1 except that 50 mL / min of nitrogen gas was blown into the oven and baked. When the MCN thus obtained was analyzed by X-ray diffraction in the same manner as MCA, it was confirmed to be molybdenum trioxide.
The average size of the plate-like particles of MCN particles observed using a field emission scanning electron microscope was 1 μm in length, 1.5 μm in width, and 40 to 80 nm in thickness.
The R value, A value and surface area of MCN were measured in the same manner as MCA. The respective values are shown in Table 1.

[Synthesis Example 3: Synthesis of MSEA]
A 2 L beaker was charged with 500 mL water and 7.5 g AHM and stirred at room temperature for 4.5 minutes. Subsequently, 1 L of acetone was added to the beaker and stirred for 7 minutes. Thereafter, AHM was separated by filtration. The AHM was washed twice with 100 mL acetone, followed by 2 washes with 20 mL pentane. Thereafter, the AHM was dried at 80 ° C. for 14 hours to obtain an AHM in which impurities were solvent extracted.
Subsequently, AHM was calcined under an air stream in the same manner as in Synthesis Example 1 to obtain MSEA. When MSEA thus obtained was analyzed by X-ray diffraction in the same manner as MCA, it was confirmed to be molybdenum trioxide.
The average size of the plate-like particles of MSEA particles observed using a field emission scanning electron microscope was 1 μm in length, 2 μm in width, and 30 to 60 nm in thickness.
MSEA R, A and surface areas were measured in the same manner as MCA. The respective values are shown in Table 1.

[Synthesis Example 4: Synthesis of MSEN]
In the same manner as in Synthesis Example 3, an AHM in which impurities were solvent extracted was obtained. The AHM was baked under a nitrogen stream to obtain MSCN. When MSEN thus obtained was analyzed by X-ray diffraction in the same manner as MCA, it was confirmed that there was no molybdenum trioxide and that it was Mo ₄ O ₁₁ .

[Synthesis Example 5: Synthesis of Silylated MCA-1]
A 100 mL flask equipped with a condenser was prepared and charged with 1.0 g MCA. The flask was purged with argon gas.
0.5 mL of methoxytrimethylsilane was dissolved in 25 mL of toluene dried using NaH to prepare a toluene solution of methoxytrimethylsilane. The toluene solution was charged into the flask, and the flask was heated in an oil bath to react methoxytrimethylsilane and MCA under toluene reflux for 24 hours. The reaction was performed under an argon gas stream.
Subsequently, the MCA was filtered, washed with 200 mL of toluene, washed with 10 mL of acetonitrile three times, and further washed with 10 mL of pentane three times.
The silylated MCA thus obtained was dried at 120 ° C. for 14 hours under an argon gas stream.

[Synthesis Example 6: Synthesis of Silylated MCA-2]
Silylated MCA-2 was synthesized in the same manner as in Synthesis Example 5 except that ethoxytrimethylsilane was used instead of methoxytrimethylsilane.

[Example 1: Production of diarylmethane compound using MSEA]
A 50 mL three-necked flask equipped with a condenser was prepared. The flask was charged with 0.3 g of MSEA and a magnetic stirrer. The flask was purged with argon gas at 20 mL / min, sealed, heated in an oil bath, and kept at 120 ° C. for 20 minutes.

The flask was removed from the oil bath and air cooled to room temperature. In this state, 0.24 mL of benzyl alcohol, 15 mL of toluene, and 0.1 mL of hexadecane as an internal standard were charged into the flask. After introducing 10 mL / min of argon gas into the flask for 3 minutes, 5 mL / min of argon gas was introduced into the flask.
The flask was heated in an oil bath at 116 ° C., and toluene and benzyl alcohol were reacted under reflux of toluene. 0.1 mL of the reaction solution was sampled every 5 minutes for analysis, and the reaction was followed. The collected reaction solution was filtered with a 0.2 μm membrane filter, and the filtrate was analyzed with GC / Mass (M-100QA, manufactured by Anelva).

The residue of the filtrate was analyzed by ¹ H-NMR. ¹ H-NMR was performed at 23 ° C. using d ⁶ -DMSO by ECX-600 and ECX-400 manufactured by JEOL Ltd.

Thus, reaction was performed for 10 minutes and the diarylmethane compound represented by Formula (C2) was isolated. The conversion rate of benzyl alcohol in this reaction was 100%, and the yield was 95%. In this reaction, an isomer in which the bonding site of the methylene group is ortho, meta or para in the formula (C2) with respect to the methyl group is obtained. Therefore, the yield was a value obtained by dividing the total mass of the isomer by the theoretical yield.
As shown in Table 1, the ratio of the isomers of the diarylmethane compound in this example is ortho / meta / para = 44/10/46, and it is clear that the ortho and para isomers are selectively obtained. It became.
MSEA used in this example had an R value of 90%, an A value of 9 m ² / g, and a surface area by BET method of 10 m ² / g.

[Example 2: Production of diarylmethane compound using MCN]
A diarylmethane compound was produced in the same manner as in Example 1 except that MCN was used instead of MSEA as molybdenum trioxide. The conversion rate of benzyl alcohol in this reaction was 100%, and the yield was 95%. As shown in Table 1, the ratio of isomers of the obtained diarylmethane compound was ortho / meta / para = 45/9/46, and ortho and para were selectively obtained.
The MCN used in this example had an R value of 86%, an A value of 9 m ² / g, and a surface area by BET method of 11 m ² / g.

[Example 3: Production of diarylmethane compound using MCA]
A diarylmethane compound was produced in the same manner as in Example 1 except that MCA was used instead of MSEA as molybdenum trioxide and the reaction time was changed from 10 minutes to 20 minutes. The conversion rate of benzyl alcohol in this reaction was 100%, and the yield was 95%. As shown in Table 1, the ratio of isomers of the obtained diarylmethane compounds was ortho / meta / para = 44/9/47, and ortho and para isomers were selectively obtained.
The MCA used in this example had an R value of 50%, an A value of 3 m ² / g, and a surface area by the BET method of 6 m ² / g.

[Example 4: Production of diarylmethane compound using commercially available molybdenum trioxide]
A diarylmethane compound was produced in the same manner as in Example 1 except that commercially available molybdenum trioxide was used instead of MSEA as molybdenum trioxide, and the reaction time was changed from 10 minutes to 30 minutes. The conversion of benzyl alcohol in this reaction was 54%. As shown in Table 1, the ratio of isomers of the obtained diarylmethane compounds was ortho / meta / para = 44/9/47, and ortho and para isomers were selectively obtained.
The commercially available molybdenum trioxide used in this example had an R value of 45%, an A value of 1 m ² / g, and a surface area by the BET method of 2 m ² / g.

[Comparative Example 1: Production of diarylmethane compound using molybdenum dioxide]
A diarylmethane compound was produced in the same manner as in Example 1 except that commercially available molybdenum dioxide was used instead of MSEA as molybdenum trioxide, and the reaction time was changed from 10 minutes to 260 minutes. However, the conversion rate of benzyl alcohol in this reaction was 11%, which revealed that the reaction did not proceed sufficiently. As shown in Table 2, the ratio of isomers of the obtained diarylmethane compound was ortho / meta / para = 48/6/46, and the ortho and para isomers were selectively obtained.
The commercially available molybdenum dioxide used in this example had a surface area of 1 m ² / g according to the BET method.

[Comparative Example 2: Production of diarylmethane compound using MSEN]
Synthesis of a diarylmethane compound was attempted in the same manner as in Example 1 except that MSEN was used instead of MSEA as molybdenum trioxide and the reaction time was changed from 10 minutes to 20 minutes. However, the conversion of benzyl alcohol in this reaction was 0%, and no diarylmethane compound was obtained.

[Example 5: Production of diarylmethane compound using benzene]
A diarylmethane compound was synthesized in the same manner as in Example 3 except that benzene was used instead of toluene, the oil bath temperature was changed from 116 ° C. to 85 ° C., and the reaction time was changed from 20 minutes to 90 minutes. The conversion rate of benzyl alcohol in this reaction was 100%, and the yield was 94%.

[Example 6: Production of diarylmethane compound using anisole]
A diarylmethane compound was synthesized in the same manner as in Example 3 except that anisole was used instead of toluene. The conversion rate of benzyl alcohol in this reaction was 100%, and the yield was 94%. As shown in Table 3, an isomer having a methylene group bonded to the ortho-position and para-position to the methoxy group was obtained as a diarylmethane compound, but an isomer having a methylene group bonded to the meta-position was obtained. There wasn't. Due to the strong ortho and para orientation in the electrophilic substitution reaction of anisole, extremely high reaction selectivity was shown.

[Example 7: Production of diarylmethane compound using p-xylene]
A diarylmethane compound was synthesized in the same manner as in Example 3 except that p-xylene was used instead of toluene, the oil bath temperature was changed from 116 ° C. to 144 ° C., and the reaction time was changed from 20 minutes to 10 minutes. The conversion rate of benzyl alcohol in this reaction was 100%, and the yield was 93%.

[Example 8: Production of diarylmethane compound using ethylbenzene]
A diarylmethane compound was synthesized in the same manner as in Example 3 except that ethylbenzene was used instead of toluene, the oil bath temperature was changed from 116 ° C. to 144 ° C., and the reaction time was changed from 20 minutes to 5 minutes. The conversion rate of benzyl alcohol in this reaction was 100%, and the yield was 93%. As a diarylmethane compound, as shown in Table 3, an isomer in which a methylene group was bonded to the ortho, meta, and para positions with respect to the ethyl group was obtained. The ratio was ortho isomer / meta isomer / para isomer = 42/12/46, and ortho and para isomers were selectively obtained.

[Example 9: Production of diarylmethane compound using mesitylene]
A diarylmethane compound was synthesized in the same manner as in Example 3 except that mesitylene was used instead of toluene, the oil bath temperature was changed from 116 ° C. to 146 ° C., and the reaction time was changed from 20 minutes to 5 minutes. The conversion rate of benzyl alcohol in this reaction was 100%, and the yield was 95%.

[Example 10: Production of diarylmethane compound using naphthalene]
A diarylmethane compound was produced in the same manner as in Example 3, using 0.78 mmol of naphthalene, 26 μmol of benzyl alcohol, 30 μL of hexadecane as an internal standard, 30 mg of MCA, and 2 mL of 1,4-dioxane as a solvent. The oil bath temperature in the reaction was 106 ° C., and the reaction time was 120 minutes. The conversion of benzyl alcohol in this reaction was 95%.
As a diarylmethane compound, as shown in Table 3, isomers in which the methylene group binding sites were the 1-position and 2-position of naphthalene were obtained. The ratio was 1-position / 2-position = 74/26, and the 1-position was selectively obtained. It was inferred that the reactivity of naphthalene had an effect.

The results of Examples 5-10 are shown in Table 3.

[Example 11: Production of cyclic organic compound]
An intramolecular dehydration reaction was performed in the same manner as in Example 1 using 15 mmol of (2-benzylphenyl) methanol, 3.0 mL of 1,4-dioxane as a solvent, and 0.1 g of MCA as molybdenum trioxide, and a cyclic organic compound. 9,10-dihydroanthracene was produced. The oil bath temperature was 106 ° C., and the reaction time was 4 hours.
The conversion rate of (2-benzylphenyl) methanol in this reaction was 97%.

[Example 12: Production of cyclic organic compound]
The cyclic organic compound 10,11-dihydro-5H-dibenzo [a, except that (2-phenylethylphenyl) methanol is used instead of (2-benzylphenyl) methanol, in the same manner as in Example 10. d] Cycloheptene was produced. The oil bath temperature was 106 ° C., and the reaction time was 4 hours.
The conversion rate of (2-benzylphenyl) methanol in this reaction was 42%. The reason why the conversion rate was lower than that of Example 11 was presumed that the cyclopentane ring was an unstable compound having higher strain energy than the cyclohexane ring.

The results of Examples 11 and 12 are shown in Table 4.

[Example 13: Recyclability of molybdenum trioxide]
In the same manner as in Example 1, a diarylmethane compound was produced (first reaction). The mixture after the reaction was filtered through a 0.2 μm membrane filter (manufactured by Toyo Roshi Kaisha, Ltd.), and MSEA was separated by filtration. The filtered MSEA was washed 5 times with 3 mL of toluene.
New benzyl alcohol and toluene were prepared, and the diarylmethane compound was produced in the same manner as in Example 1 using the MSEA (second reaction). After completion of the reaction, MSEA was filtered and washed by the method described above.
The same reaction was repeated using the same MSEA, and the seventh reaction was performed. As a result, also in the seventh reaction, a diarylmethane compound was obtained with the same conversion rate, yield and selectivity as in Example 1. This revealed that the MSEA of the present invention is excellent in recyclability.

[Example 14: Production of diarylmethane compound using silylated MCA-1]
A diarylmethane compound was produced in the same manner as in Example 3 except that silylated MCA-1 was used instead of MCA. As a result, a diarylmethane compound was obtained with the same conversion rate, yield and selectivity as in Example 3.

[Example 15: Production of diarylmethane compound using silylated MCA-2]
A diarylmethane compound was produced in the same manner as in Example 3 except that silylated MCA-2 was used instead of MCA. As a result, a diarylmethane compound was obtained with the same conversion rate, yield and selectivity as in Example 3.

  Silylated MCA has almost no hydroxyl group on the surface of molybdenum trioxide because the hydroxyl group present on the surface of molybdenum trioxide is reacted with alkoxylsilane. However, the results of Examples 13 and 14 were almost the same as the results of Example 3 using MCA. This suggests that the hydroxyl group present on the surface of molybdenum trioxide is not involved in the reaction of the present invention.

[Comparative Example 3]
Production of a diarylmethane compound was attempted in the same manner as in Example 1 except that pyridine having the same number of moles as benzyl alcohol was added. However, a diarylmethane compound was not obtained. From this result, it is clear that the reaction is inhibited in the presence of a Lewis base such as pyridine. It was assumed that the Lewis acid site of molybdenum trioxide was inactivated by the reaction of the Lewis acid site of molybdenum trioxide with pyridine. That is, it was speculated that the Lewis acid site of molybdenum trioxide was greatly involved in the reaction of the present invention.

  By this reaction, a diarylmethane compound or a cyclic organic compound can be obtained in good yield under mild conditions. The present invention is useful as a method for producing a diarylmethane compound or a cyclic organic compound, which is a raw material for pharmaceuticals and chemical products.

Claims (5)

(A) an aromatic compound represented by the general formula (A1) or (A2);
(B) benzyl alcohol which may have a substituent, or naphthalenemethanol which may have a substituent,
A method for producing a diarylmethane compound, wherein a dehydration reaction is performed in the presence of crystalline molybdenum trioxide.

[In Formula (A1), R ₁ is a substituent, which is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
x is the number of R ₁ and is an integer of 0 to 5;
when x is 2-5, each R ₁ may be different]

[In the formula (A2), R ₂ is a substituent at the 1 to 8 position of the naphthalene ring, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
y is the number of R ₂ and an integer of 0 to 7;
when y is 2-7, each R ₂ may be different] (D) A method for producing a cyclic organic compound represented by the general formula (E), wherein the alcohol represented by the general formula (D1) is subjected to an intramolecular dehydration reaction in the presence of crystalline molybdenum trioxide.

[In the formula (D1), the number is a position number;
R ₃ is a substituent at the ₃ ′ to 6 ′ position and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
p is the number of R ₃ and is an integer of 0 to 4; when p is 2 to 4, each R ₃ may be different;
R ₄ is a substituent at the 3-6 position, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
q is the number of R ₄ and is an integer of 0 to 4; when q is 2 to 4, each R ₄ may be different;
n is 1 or 2]

[In the formula (E), the number is a position number;
R ₃ is a substituent at the 5- to 8-position, and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
p is the number of R ₃ and is an integer of 0 to 4; when p is 2 to 4, each R ₃ may be different;
R ₄ is a substituent at the 1 to 4 position and is an alkyl group having 1 to 4 carbon atoms or an alkoxyl group having 1 to 4 carbon atoms;
q is the number of R ₄ and is an integer of 0 to 4; when q is 2 to 4, each R ₄ may be different;
n is 1 or 2]   The crystalline molybdenum trioxide is plate-like, and the average size of the plate-like particles measured using a field emission scanning electron microscope is 0.5 to 2 μm in length, 1 to 3 μm in width, and 30 to 30 in thickness. The manufacturing method of Claim 1 or 2 which is 200 nm.   The manufacturing method of Claim 3 whose ratio of the area of the plate-shaped surface which occupies for the total surface area of the said crystalline molybdenum trioxide is 60 to 95%. The manufacturing method of Claim 3 whose area of the plate-shaped surface of the said crystalline molybdenum trioxide is 5-20 m < ² > / g.