JP5488834B2 - Method for producing 2-hydroxyarylaldehyde compound - Google Patents

Description

  The present invention relates to a method for producing a 2-hydroxyaryl aldehyde compound useful as a material for a photosensitive resist composition, a curing agent, a developer, or a ligand intermediate of an asymmetric synthesis catalyst.

Numerous methods have been reported for the formylation of aromatic compounds (Non-patent Document 1).
Examples of a method for producing an arylaldehyde compound by formylating a hydroxyaryl compound include the following methods.
(Conventional method 1) Gattermann method: A method of producing an aryl aldehyde compound by reacting hydrogen cyanide with a hydroxyaryl compound or reacting cyanogen zinc with hydrogen chloride using aluminum chloride or zinc chloride as a catalyst (non-patented) Reference 2, non-patent reference 3).
(Conventional method 2) Gattermann-Koch method: A method of producing an aryl aldehyde compound by reacting carbon monoxide and hydrogen chloride in the presence of aluminum chloride and copper chloride (Non-patent Document 4).
(Conventional method 3) A method using formyl fluoride and boron trifluoride (Non-patent Document 5).
(Conventional method 4) Method using dichloromethyl alkyl ether or orthoformate; reacting dichloromethyl alkyl ether or orthoformate in the presence of titanium tetrachloride, aluminum chloride or tin chloride, followed by hydrolysis And a method for producing an arylaldehyde compound (Non-patent Document 6).
(Conventional method 5) Vilsmeier-Haack method; a method for producing an arylaldehyde compound by reacting phosphorus oxychloride, thionyl chloride or oxalyl chloride with a compound obtained by reacting with an N-substituted formamide compound (Non-patent Document 7) Non-patent document 8).
(Conventional method 6) Reimer-Tiemann reaction; a method of producing an arylaldehyde compound by reacting chloroform, bromoform, trichloroacetic acid or the like in the presence of alkali (Non-patent Document 9).
(Conventional method 7) Duff reaction; a method of producing an aryl aldehyde compound by reacting hexamethylenetetramine in the presence of boric acid glycerin ester, acetic acid or trifluoroacetic acid (Non-patent Documents 10 and 11).
(Conventional method 8) Catalytic method using a formaldehyde compound (paraformaldehyde, formalin, etc.); As a catalyst, a tin chloride compound (Non-patent Document 12), a titanium compound or a zirconium compound (Patent Document 1, Patent Document 2), etc. is there.
(Conventional Method 9) A method for producing an aryl aldehyde compound by reacting with a 1: 1 complex of aryloxymagnesium bromide and hexamethylphosphoramide (HMPA) using paraformaldehyde (Non-patent Document 13, Non-patent Document) Reference 14 and Non-Patent Reference 15)
(Conventional method 10) A method for producing an aryl aldehyde compound by using paraformaldehyde and reacting with a phenoxy magnesium salt compound prepared from magnesium methoxide and a phenol compound (Patent Document 3, Non-Patent Document 16)
(Conventional method 11) A method of producing an arylaldehyde compound from a hydroxyaryl compound by reacting with a combination of magnesium chloride and triethylamine using paraformaldehyde (Non-patent Document 17, Non-patent Document 18)
(Conventional method 12) A method for producing an aryl aldehyde compound by deprotection of a methoxymethyl group by using a compound in which a hydroxyaryl compound is protected with a methoxymethyl group, lithiation and formylation, and deprotecting the methoxymethyl group (Non-patent Document 19)

Japanese Patent Laid-Open No. 58-72536 JP 59-73537 A Japanese Patent No. 3373228

Chem. Rev. (1987), 87, 671-686. Organic Reactions (1957), 9, 37-72. J. et al. Am. Chem. Soc. (1923), 45, 2373-2377. Ber. (1897), 30, 1622-1624. J. et al. Am. Chem. Soc. (1960), 82, 2380-2382. Chem. Ber. (1960), 93, 88-94. Ber. (1927), 60B, 119-122. Organic Synthesis Collective Volume 3 (1955), 98-100. Ber. (1876), 9, 423-424. Chem. Rev. (1946), 38, 227-254. J. et al. Org. Chem. (1994), 59, 1939-1942. J. et al. Chem. Soc. Perkin Trans I. (1980), 1862-1865. J. et al. Chem. Soc. Perkin Trans I. (1978), 318-321. J. et al. Org. Chem. (1993), 58, 1515-1522. Bioorganic & Medicinal Chemistry (2007), 15, 3783-3800 (page 3793). J. et al. Chem. Soc. Perkin Trans I. (1994), 1823-1831. Acta. Chemica. Scandinavica. (1999), 53, 258-262. Organic Synthesis, (2005), 82, 64-67. Synthetic Communications (1975), 5 (1), 65-78.

  In these methods, the methods from (Conventional Method 1) to (Conventional Method 7) are toxic to the raw materials, and the products and by-products derived from the reaction are corrosive to the reactor. It is hard to say that this is an advantageous method from an industrial point of view. In addition, the yield is often moderate, and depending on the raw material, there are problems that it can be obtained only in a low yield and that a by-product is generated.

  In the method of (Conventional Method 8), the tin chloride compound used as a catalyst is toxic. When a titanium compound or a zirconium compound is used as a catalyst, a reaction temperature of 150 ° C. or higher is required, and it is difficult to say that the method is advantageous from an industrial standpoint from the viewpoint of yield and by-product formation. In the method of (Conventional Method 9), the hexamethylphosphoramide (HMPA) used is a carcinogenic substance, and a Grignard reagent or toxic benzene is used to prepare aryloxymagnesium bromide. It is difficult to say that this method is advantageous from an industrial point of view. Further, improved methods are described in Non-Patent Document 14 and Non-Patent Document 15, but the use of Grignard reagent or hexamethylphosphoramide (HMPA) cannot be avoided. The method of (Conventional Method 10) uses a toluene solvent, and there are examples of good results in terms of the yield of the product aldehyde, but in the reaction substrate, a by-product diarylmethane compound is produced. Also, the preparation of the phenoxymagnesium salt compound is difficult to say from the viewpoint of industrial work in terms of solvent removal by distillation.

The method of (Conventional Method 11) is an improved method in which formylation by Casiraghi et al. Is simplified (Non-Patent Document 12, Non-Patent Document 13). A method for producing a compound. Although the use of hexamethylphosphoramide (HMPA), which is a carcinogenic substance, was avoided and the yield was improved as compared to formylation by Casiraghi et al., There was a problem with by-products.
The method of (Conventional Method 12) is a method that can be selectively formylated at the ortho position of the hydroxyaryl compound. However, when an object having a substituent is obtained, it cannot be achieved by a one-step reaction, and the substituent is protected. , A formylation reaction, deprotection of substituents and a three-stage reaction are required, which is difficult to say from an industrial point of view. Furthermore, this method has a problem in that, for a hydroxyaryl compound whose substituent is halogen or a hydroxyaryl compound having a benzyl moiety, the lithiation reaction cannot be controlled and a by-product is generated.

  Thus, an industrially useful production method of 2-hydroxyaryl aldehyde compounds that can achieve both suppression of by-products and improvement in yield is continuously demanded.

  As a result of diligent research on industrially useful production methods for 2-hydroxyaryl aldehyde compounds, the inventors have used paraformaldehyde and reacted with a combination of magnesium chloride and triethylamine to convert 2-hydroxyaryl aldehydes from 2-hydroxyaryl aldehyde compounds. Focusing on methods for producing aldehyde compounds (Non-Patent Document 17, Non-Patent Document 18), with respect to triethylamine used as a base function in the reaction, (i) a function as a base and (ii) a magnesium reaction By using an amine compound that becomes a multidentate ligand having a ligand function that stabilizes the intermediate in the reaction, the by-product is suppressed and the chemical yield is higher than that of the conventional technique. The present inventors have found that a hydroxyaryl aldehyde compound can be produced and completed the present invention.

（式（１）中のＲ¹、Ｒ²、Ｒ³及びＲ⁴は、それぞれ独立に水素原子、１ないし３のフェニル基（該フェニル基は無置換であるか、又は置換基Ａ及びヒドロキシ基から選ばれる同一又は相異なった１以上の置換基で置換されている。）で置換され、さらにＣ_1-4アルキル基及びハロゲン原子から選ばれる同一又は相異なった１以上の置換基で置換されていてもよいＣ_1-4アルキル基、１ないし３のフェニル基（該フェニル基は無置換であるか、又は置換基Ａ及びヒドロキシ基から選ばれる同一又は相異なった１以上の置換基で置換されている。）で置換されたフェニル基、フェニルカルボニル基（該フェニルカルボニル基は無置換であるか、又は置換基Ａ及びヒドロキシ基から選ばれる同一又は相異なった１以上の置換基で置換されている。）、フェニルスルホニル基（該フェニルスルホニル基は無置換であるか、又は置換基Ａ及びヒドロキシ基から選ばれる同一又は相異なった１以上の置換基で置換されていてもよい。）又は置換基Ａであり、
Ｒ²とＲ³とは一緒になって−ＣＲ⁵＝ＣＲ⁶−ＣＲ⁷＝ＣＲ⁸−を形成していても良く、このときＲ⁵、Ｒ⁶、Ｒ⁷及びＲ⁸は、それぞれ独立に水素原子又は置換基Ａであり、
置換基Ａは、ハロゲン原子、Ｃ_1-4アルキル基、Ｃ_1-4ハロアルキル基、Ｃ_1-4アルコキシ基、Ｃ_6-12アリールオキシ基、Ｃ_6-22アリール基（該アリールオキシ基及び該アリール基は、無置換であるか、又はＣ_1-4アルキル基、Ｃ_1-4ハロアルキル基、Ｃ_1-4アルコキシ基、Ｃ_1-4アルキルカルボニルオキシ基、Ｃ_6-12アリール基（該アリール基は、無置換であるか、又はＣ_1-4アルキル基、Ｃ_1-4ハロアルキル基及びＣ_1-4アルコキシ基から選ばれる同一又は相異なった１以上の置換基で置換されている。）、ｔ−ブチルジメチルシリル基、Ｃ_6-22アリールメチルオキシ基（該アリールメチルオキシ基は、無置換であるか、又はＣ_1-4アルキル基、Ｃ_1-4アルコキシ基、ハロゲン原子及びフェニル基から選ばれる同一又は相異なった１以上の置換基で置換されている。）及びハロゲン原子から選ばれる同一又は相異なった１以上の置換基で置換されている。）、ニトロ基又はシアノ基から選ばれる置換基である。）で表されるヒドロキシアリール化合物を、式（ａ）

（式（ａ）中のＲ⁹はＣ_1-3アルキル基であるか、又は同じ窒素原子上の２つのＲ⁹が一緒になって＝ＣＨ−Ｒ¹⁰を表し、
Ｒ¹⁰はＣ_6-12アリール基（該アリール基は、無置換であるか、又はＣ_1-4アルキル基、Ｃ_1-4アルコキシ基及びハロゲン原子から選ばれる同一又は相異なった１以上の置換基で置換されている。）であり、
ｎは０又は１から１０までの整数である。）で表されるアミン化合物存在下、無水塩化マグネシウム及びパラホルムアルデヒドと反応させることにより、ヒドロキシアリール化合物のオルト位選択的にホルミル化することを特徴とする下記式（２）

（上記式中のＲ¹、Ｒ²、Ｒ³及びＲ⁴は前記と同じである。）で表される２−ヒドロキシアリールアルデヒド化合物の製造方法。That is, the present invention
[1] Formula (1)

(In the formula (1), R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom, 1 to 3 phenyl groups (the phenyl group is unsubstituted or a substituent A and a hydroxy group) And substituted with one or more substituents selected from the same or different ones selected from C _1-4 alkyl groups and halogen atoms. An optionally substituted C _1-4 alkyl group, 1 to 3 phenyl groups (the phenyl group is unsubstituted or substituted with one or more substituents selected from the same or different substituents A and hydroxy groups). A phenyl group substituted with one or more substituents selected from the same or different substituents selected from the substituent A and a hydroxy group. ing.) A phenylsulfonyl group (the phenylsulfonyl group may be unsubstituted, or may be substituted with one or more substituents selected from the substituent A and a hydroxy group) or a substituent A ,
R ² and R ³ may be combined to form —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ —, in which R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently A hydrogen atom or a substituent A,
Substituent A includes a halogen atom, a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _6-12 aryloxy group, a C _6-22 aryl group (the aryloxy group and the The aryl group may be unsubstituted or C _1-4 alkyl group, C _1-4 haloalkyl group, C _1-4 alkoxy group, C _1-4 alkylcarbonyloxy group, C _6-12 aryl group (the aryl group). The group is unsubstituted or substituted with one or more substituents which are the same or different and are selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group. , T-butyldimethylsilyl group, C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or C _1-4 alkyl group, C _1-4 alkoxy group, halogen atom and phenyl group) Substituted with one or more substituents selected from Are.) And is substituted with one or more substituents the same or different selected from halogen atom.), A substituent selected from nitro group or a cyano group. A hydroxyaryl compound represented by formula (a)

(R ⁹ in formula (a) is a C _1-3 alkyl group, or two R ⁹ on the same nitrogen atom together represent ═CH—R ¹⁰ ;
R ¹⁰ represents a C _6-12 aryl group (the aryl group is unsubstituted or one or more substituents selected from a C _1-4 alkyl group, a C _1-4 alkoxy group and a halogen atom). Substituted with a group)
n is 0 or an integer from 1 to 10. In the presence of an amine compound represented by the following formula (2):

(Wherein R ¹ , R ² , R ³ and R ⁴ are the same as described above).

[2] R ¹ is a hydrogen atom, a phenyl group (the phenyl group is unsubstituted or a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 alkyl A carbonyloxy group, a C _6-12 aryl group (the aryl group is unsubstituted or the same or different selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group) A C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or a C _1-4 alkyl group, a C _1-4 alkoxy group). Substituted with one or more substituents selected from the same or different from each other selected from a halogen atom and a phenyl group.) Or substituted with one or more substituents selected from the same or different from a halogen atom. A naphthyl group (the naphthyl group is unsubstituted or Is a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 alkylcarbonyloxy group, a C _6-12 aryl group (the aryl group is unsubstituted or Substituted with one or more of the same or different substituents selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group.), T-butyldimethylsilyl group, C _{6 -22} arylmethyloxy group (the arylmethyloxy group is unsubstituted or one or more same or different selected from C _1-4 alkyl group, C _1-4 alkoxy group, halogen atom and phenyl group) And is substituted with one or more substituents selected from the same or different ones selected from halogen atoms, and is optically active or optically inactive.
R ² is a hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, i-propyl group, t-butyl group, trifluoromethyl group or pentafluoroethyl group, and R ³ and R ⁴ are each independently hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, i-propyl group, t-butyl group, trifluoromethyl group, methoxy group, ethoxy group, i-propoxy The production method of [1], which is a group or a t-butoxy group.

[3] R ¹ is a hydrogen atom, a phenyl group (the phenyl group is unsubstituted or a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 alkyl A carbonyloxy group, a C _6-12 aryl group (the aryl group is unsubstituted or the same or different selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group) A C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or a C _1-4 alkyl group, a C _1-4 alkoxy group). Substituted with one or more substituents selected from the same or different from each other selected from a halogen atom and a phenyl group.) Or substituted with one or more substituents selected from the same or different from a halogen atom. A naphthyl group (the naphthyl group is unsubstituted or Is a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 alkylcarbonyloxy group, a C _6-12 aryl group (the aryl group is unsubstituted or Substituted with one or more of the same or different substituents selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group.), T-butyldimethylsilyl group, C _{6 -22} arylmethyloxy group (the arylmethyloxy group is unsubstituted or one or more same or different selected from C _1-4 alkyl group, C _1-4 alkoxy group, halogen atom and phenyl group) And is substituted with one or more substituents selected from the same or different ones selected from halogen atoms, and is optically active or optically inactive.
R ² and R ³ together represent —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ —, and R ⁵ and R ⁷ are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom. , Methyl group, ethyl group, i-propyl group, t-butyl group, trifluoromethyl group, methoxy group, ethoxy group, i-propoxy group or t-butoxy group, R ⁶ is a hydrogen atom, a fluorine atom, chlorine In [1], an atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, an i-propyl group, a t-butyl group, a trifluoromethyl group or a pentafluoroethyl group, and R ⁸ is a hydrogen atom or a fluorine atom The manufacturing method as described.

[4] R ⁹ is a methyl group, two R ⁹ on the ethyl group or the same nitrogen atom together form = represents CH-R ^10, R ¹⁰ is a phenyl group, 2-fluorophenyl group, 2-methylphenyl [1] The production method according to [1], which is a 2-methoxyphenyl group or a 2-i-propoxyphenyl group.

  According to the present invention, a 2-hydroxyaryl aldehyde compound can be produced with high chemical yield while suppressing by-products. The hydroxyaryl aldehyde compound that can be produced in the present invention is useful as a material for photosensitive resist compositions, a curing agent, a developer, a ligand intermediate of an asymmetric synthesis catalyst, and the like.

As used herein, “n” is normal, “i” is iso, “s” is secondary, “t” is tertiary, “c” is cyclo, “o” is ortho, “m” Means meta, “p” means para. Further, “Me” represents a methyl group, “Et” represents an ethyl group, “Bu” represents a butyl group, “TMEDA” represents N, N, N ′, N′-tetramethylethylenediamine, and “THF” represents tetrahydrofuran. “Et ₂ O” means diethyl ether.

（式（１）中のＲ¹、Ｒ²、Ｒ³及びＲ⁴は、それぞれ独立に水素原子、１ないし３のフェニル基（該フェニル基は無置換であるか、又は置換基Ａ及びヒドロキシ基から選ばれる同一又は相異なった１以上の置換基で置換されている。）で置換され、さらにＣ_1-4アルキル基及びハロゲン原子から選ばれる同一又は相異なった１以上の置換基で置換されていてもよいＣ_1-4アルキル基、１ないし３のフェニル基（該フェニル基は無置換であるか、又は置換基Ａ及びヒドロキシ基から選ばれる同一又は相異なった１以上の置換基で置換されている。）で置換されたフェニル基、フェニルカルボニル基（該フェニルカルボニル基は無置換であるか、又は置換基Ａ及びヒドロキシ基から選ばれる同一又は相異なった１以上の置換基で置換されている。）、フェニルスルホニル基（該フェニルスルホニル基は無置換であるか、又は置換基Ａ及びヒドロキシ基から選ばれる同一又は相異なった１以上の置換基で置換されていてもよい。）又は置換基Ａであり、
Ｒ²とＲ³とは一緒になって−ＣＲ⁵＝ＣＲ⁶−ＣＲ⁷＝ＣＲ⁸−を形成していても良く、このときＲ⁵、Ｒ⁶、Ｒ⁷及びＲ⁸はそれぞれ独立に水素原子又は置換基Ａであり、
置換基Ａは、ハロゲン原子、Ｃ_1-4アルキル基、Ｃ_1-4ハロアルキル基、Ｃ_1-4アルコキシ基、Ｃ_6-12アリールオキシ基、Ｃ_6-22アリール基（該アリールオキシ基及び該アリール基は、無置換であるか、又はＣ_1-4アルキル基、Ｃ_1-4ハロアルキル基、Ｃ_1-4アルコキシ基、Ｃ_1-4アルキルカルボニルオキシ基、Ｃ_6-12アリール基（該アリール基は、無置換であるか、又はＣ_1-4アルキル基、Ｃ_1-4ハロアルキル基及びＣ_1-4アルコキシ基から選ばれる同一又は相異なった１以上の置換基で置換されている。）、ｔ−ブチルジメチルシリル基、Ｃ_6-22アリールメチルオキシ基（該アリールメチルオキシ基は、無置換であるか、又はＣ_1-4アルキル基、Ｃ_1-4アルコキシ基、ハロゲン原子及びフェニル基から選ばれる同一又は相異なった１以上の置換基で置換されている。）及びハロゲン原子から選ばれる同一又は相異なった１以上の置換基で置換されている。）、ニトロ基又はシアノ基から選ばれる置換基である。）で表されるヒドロキシアリール化合物と無水塩化マグネシウムとパラホルムアルデヒドと式（ａ）

（式（ａ）中のＲ⁹はＣ_1-3アルキル基であるか、又は同じ窒素原子上の２つのＲ⁹が一緒になって＝ＣＨ−Ｒ¹⁰を表し、
Ｒ¹⁰はＣ_6-12アリール基（該アリール基は、無置換であるか、又はＣ_1-4アルキル基、Ｃ_1-4アルコキシ基及びハロゲン原子から選ばれる同一又は相異なった１以上の置換基で置換されている。）であり、
ｎは０又は１から１０までの整数である。）で表されるアミン化合物存在下、トリエチルアミンの存在下又は非存在下、無水塩化マグネシウム及びパラホルムアルデヒドと反応させることにより、ヒドロキシアリール化合物のオルト位選択的にホルミル化することにより下記式（２）

（上記式中のＲ¹、Ｒ²、Ｒ³及びＲ⁴は前記と同じである。）で表される２−ヒドロキシアリールアルデヒド化合物を製造できることが特徴である。The present invention is described in detail below. The method for producing a 2-hydroxyaryl aldehyde compound of the present invention is represented by the formula (1).

(In the formula (1), R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom, 1 to 3 phenyl groups (the phenyl group is unsubstituted or a substituent A and a hydroxy group) And substituted with one or more substituents selected from the same or different ones selected from C _1-4 alkyl groups and halogen atoms. An optionally substituted C _1-4 alkyl group, 1 to 3 phenyl groups (the phenyl group is unsubstituted or substituted with one or more substituents selected from the same or different substituents A and hydroxy groups). A phenyl group substituted with one or more substituents selected from the same or different substituents selected from the substituent A and a hydroxy group. ing.) A phenylsulfonyl group (the phenylsulfonyl group may be unsubstituted, or may be substituted with one or more substituents selected from the substituent A and a hydroxy group) or a substituent A ,
R ² and R ³ may be combined to form —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ —, wherein R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently hydrogen. An atom or substituent A,
Substituent A includes a halogen atom, a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _6-12 aryloxy group, a C _6-22 aryl group (the aryloxy group and the The aryl group may be unsubstituted or C _1-4 alkyl group, C _1-4 haloalkyl group, C _1-4 alkoxy group, C _1-4 alkylcarbonyloxy group, C _6-12 aryl group (the aryl group). The group is unsubstituted or substituted with one or more substituents which are the same or different and are selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group. , T-butyldimethylsilyl group, C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or C _1-4 alkyl group, C _1-4 alkoxy group, halogen atom and phenyl group) Substituted with one or more substituents selected from Are.) And is substituted with one or more substituents the same or different selected from halogen atom.), A substituent selected from nitro group or a cyano group. ) Hydroxyaryl compound, anhydrous magnesium chloride, paraformaldehyde and formula (a)

(R ⁹ in formula (a) is a C _1-3 alkyl group, or two R ⁹ on the same nitrogen atom together represent ═CH—R ¹⁰ ;
R ¹⁰ represents a C _6-12 aryl group (the aryl group is unsubstituted or one or more substituents selected from a C _1-4 alkyl group, a C _1-4 alkoxy group and a halogen atom). Substituted with a group)
n is 0 or an integer from 1 to 10. In the presence or absence of triethylamine in the presence or absence of an amine compound represented by the following formula (2):

(R ¹ , R ² , R ^3, and R ⁴ in the above formula are the same as described above).

Each substituent and partial structure in the formula (1) and formula (2) will be described.
R ¹ , R ² , R ³ and R ⁴ in formula (1) and formula (2) are each independently a hydrogen atom, 1 to 3 phenyl groups (the phenyl group is unsubstituted or substituted) Substituted with one or more substituents selected from the group A and a hydroxy group), and further, one or more same or different selected from a C _1-4 alkyl group and a halogen atom. A C _1-4 alkyl group which may be substituted with a substituent, 1 to 3 phenyl groups (the phenyl group is unsubstituted or the same or different one or more selected from the substituent A and a hydroxy group) A phenyl group or a phenylcarbonyl group (the phenylcarbonyl group is unsubstituted, or is the same or different from one selected from the substituent A and a hydroxy group). Substitute with substituent A phenylsulfonyl group (the phenylsulfonyl group may be unsubstituted or substituted by one or more substituents selected from the substituent A and a hydroxy group). Or a substituent A,
R ² and R ³ may be combined to form —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ —, wherein R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently hydrogen. An atom or substituent A,
Substituent A includes a halogen atom, a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _6-12 aryloxy group, a C _6-22 aryl group (the aryloxy group and the The aryl group may be unsubstituted or C _1-4 alkyl group, C _1-4 haloalkyl group, C _1-4 alkoxy group, C _1-4 alkylcarbonyloxy group, C _6-12 aryl group (the aryl group). The group is unsubstituted or substituted with one or more substituents which are the same or different and are selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group. , T-butyldimethylsilyl group, C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or C _1-4 alkyl group, C _1-4 alkoxy group, halogen atom and phenyl group) Substituted with one or more substituents selected from Are.) And is substituted with one or more substituents the same or different selected from halogen atom.), A substituent selected from nitro group or a cyano group.

R ¹ in Formula (1) and Formula (2) will be specifically described. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Examples of the C _1-4 alkyl group include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, an s-butyl group, and a t-butyl group. Examples of the C _1-4 alkoxy group include methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butoxy group, i-butoxy group, s-butoxy group and t-butoxy group. Examples of the C _6-12 aryloxy group include phenyloxy group, 1-naphthyloxy group, 2-naphthyloxy group, 2-biphenylyloxy group, 3-biphenylyloxy group and 4-biphenylyloxy group. It is done. The C _1-4 haloalkyl group is a fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, chlorofluoromethyl group, dichloromethyl group, bromofluoromethyl group, trifluoromethyl group, chlorodifluoromethyl group. Dichlorofluoromethyl group, trichloromethyl group, bromodifluoromethyl group, bromochlorofluoromethyl group, dibromofluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2-chloro-2-fluoroethyl group, 2,2-dichloroethyl group, 2-bromo-2-fluoroethyl group, 2,2,2-trifluoroethyl group, 2-chloro-2,2-difluoroethyl group 2,2-dichloro-2-fluoroethyl group, 2,2,2-tri Chloroethyl group, 2-bromo-2,2-difluoroethyl group, 2-bromo-2-chloro-2-fluoroethyl group, 2-bromo-2,2-dichloroethyl group, 1,1,2,2-tetra Fluoroethyl group, pentafluoroethyl group, 1-chloro-1,2,2,2-tetrafluoroethyl group, 2-chloro-1,1,2,2-tetrafluoroethyl group, 1,2-dichloro-1 , 2,2-trifluoroethyl group, 2-bromo-1,1,2,2-tetrafluoroethyl group, 2-fluoropropyl group, 2-chloropropyl group, 2-bromopropyl group, 2-chloro-2 -Fluoropropyl group, 2,3-dichloropropyl group, 2-bromo-3-fluoropropyl group, 3-bromo-2-chloropropyl group, 2,3-dibromopropyl group, 3,3,3-trifluoro Lopyl group, 3-bromo-3,3-difluoropropyl group, 2,2,3,3-tetrafluoropropyl group, 2-chloro-3,3,3-trifluoropropyl group, 2,2,3,3 , 3-pentafluoropropyl group, 1,1,2,3,3,3-hexafluoropropyl group, heptafluoropropyl group, 2,3-dichloro-1,1,2,3,3-pentafluoropropyl group 2-fluoro-1-methylethyl group, 2-chloro-1-methylethyl group, 2-bromo-1-methylethyl group, 2,2,2-trifluoro-1- (trifluoromethyl) ethyl group, 1,2,2,2-tetrafluoro-1- (trifluoromethyl) ethyl group, 2,2,3,3,4,4-hexafluorobutyl group, 2,2,3,4,4,4- Hexafluorobutyl group, 2,2,3 , 4,4,4-heptafluorobutyl group, 1,1,2,2,3,3,4,4-octafluorobutyl group, nonafluorobutyl group, 4-chloro-1,1,2,2, 3,3,4,4-octafluorobutyl group, 2-fluoro-2-methylpropyl group, 2-chloro-1,1-dimethylethyl group, 2-bromo-1,1-dimethylethyl group and the like can be mentioned. .

The C _6-22 aryl group of R ^{1 in} the formulas (1) and (2) will be described. The C _6-22 aryl group includes a phenyl group (the phenyl group is unsubstituted or a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 An alkylcarbonyloxy group, a C _6-12 aryl group (the aryl group is unsubstituted or the same or a phase selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group); Substituted with one or more different substituents), a C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or a C _1-4 alkyl group, a C _1-4 alkoxy group). Substituted with one or more substituents selected from the same or different from each other selected from a group, a halogen atom and a phenyl group.) And substituted with one or more substituents selected from the same or different from a halogen atom. , Biphenylyl group, naphthyl group (the naphthyl group is Which is unsubstituted or substituted by C _1-4 alkyl groups, C _1-4 haloalkyl group, C _1-4 alkoxy, C _1-4 alkylcarbonyloxy group, C _6-12 aryl group (the aryl group is unsubstituted Substituted or substituted with one or more substituents selected from the same or different groups selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group.), T-butyl Dimethylsilyl group, C _6-22 arylmethyloxy group (this arylmethyloxy group is unsubstituted or the same selected from C _1-4 alkyl group, C _1-4 alkoxy group, halogen atom and phenyl group) Or substituted with one or more different substituents selected from halogen atoms and substituted with one or more different substituents selected from halogen atoms, and is optically active or optically inactive. It is done.

The C _6-22 aryl group of R ^{1 in} the formulas (1) and (2) will be specifically described. The C _6-22 aryl group includes a phenyl group, a 2-methylphenyl group, a 2-trifluoromethylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2-ethylphenyl group, and 2-pentafluoroethyl. Phenyl group, 2-n-propylphenyl group, 2-i-propylphenyl group, 2-heptafluoro-n-propylphenyl group, 2-heptafluoro-i-propylphenyl group, 2-n-butylphenyl group, 2 -I-butylphenyl group, 2-s-butylphenyl group, 2-t-butylphenyl group, 2-nonafluoro-n-butylphenyl group, 2-nonafluoro-t-butylphenyl group, 2,6-dimethylphenyl group 2,6-ditrifluoromethylphenyl group, 3,5-dimethylphenyl group, 3,5-ditrifluoromethylphenyl group, 2, -Diethylphenyl group, 2,6-dipentafluoroethylphenyl group, 3,5-diethylphenyl group, 3,5-dipentafluoroethylphenyl group, 2-methoxyphenyl group, 2- (1-anthrylmethoxy) Phenyl group, 2- (2-anthrylmethoxy) phenyl group, 2- (9-anthrylmethoxy) phenyl group, 2- (1-phenanthrylmethoxy) phenyl group, 2- (2-phenanthrylmethoxy) Phenyl group, 2- (3-phenanthrylmethoxy) phenyl group, 2- (4-phenanthrylmethoxy) phenyl group, 2- (9-phenanthrylmethoxy) phenyl group, 2- (1-pyrenylmethoxy) phenyl Group, 2-mesitylmethoxyphenyl group, 2- (1-naphthylmethoxy) phenyl group, 2- (2-naphthylmethoxy) phenyl group, 2- (2-biphenylylmethoxy) phenyl group, 2- (3-biphenylylmethoxy) phenyl group, 2- (4-biphenylylmethoxy) phenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2- Ethoxyphenyl group, 3-ethoxyphenyl group, 4-ethoxyphenyl group, 2-i-propoxyphenyl group, 3-i-propoxyphenyl group, 4-i-propoxyphenyl group, 2-n-butoxyphenyl group, 2- i-butoxyphenyl group, 2-s-butoxyphenyl group, 2-t-butoxyphenyl group, 3-n-butoxyphenyl group, 3-i-butoxyphenyl group, 3-s-butoxyphenyl group, 3-t- Butoxyphenyl group, 4-n-butoxyphenyl group, 4-i-butoxyphenyl group, 4-s-butoxyphenyl group, 4-t-butoxy Enyl group, 2,6-dimethoxyphenyl group, 3,5-dimethoxyphenyl group, 2,6-diethoxyphenyl group, 3,5-diethoxyphenyl group, 2,6-di-i-propoxyphenyl group, 3 , 5-di-i-propoxyphenyl group, 2-methylcarbonyloxyphenyl group, 2-ethylcarbonyloxyphenyl group, 2-n-propylcarbonyloxyphenyl group, 2-i-propylcarbonyloxyphenyl group, 2-n -Butylcarbonyloxyphenyl group, 2-i-butylcarbonyloxyphenyl group, 2-s-butylcarbonyloxyphenyl group, 2-t-butylcarbonyloxyphenyl group, 2-benzyloxyphenyl group, 2- (2-methyl Benzyloxy) phenyl group, 2- (3-methylbenzyloxy) phenyl group, 2- (4 Methylbenzyloxy) phenyl group, 2- (2-i-propylbenzyloxy) phenyl group, 2- (3-i-propylbenzyloxy) phenyl group, 2- (4-i-propylbenzyloxy) phenyl group, 2 -(2,4,6-tri-i-propylbenzyloxy) phenyl group, 2- (2-fluorobenzyloxy) phenyl group, 2- (3-fluorobenzyloxy) phenyl group, 2- (4-fluorobenzyl) Oxy) phenyl group, 2- (2-bromobenzyloxy) phenyl group, 2- (3-bromobenzyloxy) phenyl group, 2- (4-bromobenzyloxy) phenyl group, 2- (2-methoxybenzyloxy) Phenyl group, 2- (3-methoxybenzyloxy) phenyl group, 2- (4-methoxybenzyloxy) phenyl group, 5-bromo -Phenyl group, 5-bromo-2-methylphenyl group, 5-bromo-2-trifluoromethylphenyl group, 5-bromo-3-methylphenyl group, 5-bromo-4-methylphenyl group, 5-bromo- 2-ethylphenyl group, 5-bromo-2-pentafluoroethylphenyl group, 5-bromo-2-n-propylphenyl group, 5-bromo-2-i-propylphenyl group, 5-bromo-2-heptafluoro -N-propylphenyl group, 5-bromo-2-heptafluoro-i-propylphenyl group, 5-bromo-2-n-butylphenyl group, 5-bromo-2-i-butylphenyl group, 5-bromo- 2-s-butylphenyl group, 5-bromo-2-t-butylphenyl group, 5-bromo-2-nonafluoro-n-butylphenyl group, 5-bromo-2-nonafluoro -T-butylphenyl group, 5-bromo-2,6-dimethylphenyl group, 5-bromo-2,6-ditrifluoromethylphenyl group, 5-bromo-2,6-diethylphenyl group, 5-bromo-2 , 6-dipentafluoroethylphenyl group, 5-bromo-2-methoxyphenyl group, 5-bromo-3-methoxyphenyl group, 5-bromo-4-methoxyphenyl group, 5-bromo-2-ethoxyphenyl group, 5-bromo-3-ethoxyphenyl group, 5-bromo-4-ethoxyphenyl group, 5-bromo-2-i-propoxyphenyl group, 5-bromo-3-i-propoxyphenyl group, 5-bromo-4- i-propoxyphenyl group, 5-bromo-2-n-butoxyphenyl group, 5-bromo-2-i-butoxyphenyl group, 5-bromo-2-s-butoxyphe Group, 5-bromo-2-t-butoxyphenyl group, 5-bromo-3-n-butoxyphenyl group, 5-bromo-3-i-butoxyphenyl group, 5-bromo-3-s-butoxyphenyl group 5-bromo-3-t-butoxyphenyl group, 5-bromo-4-n-butoxyphenyl group, 5-bromo-4-i-butoxyphenyl group, 5-bromo-4-s-butoxyphenyl group, 5 -Bromo-4-t-butoxyphenyl group, 5-bromo-2,6-dimethoxyphenyl group, 5-bromo-2,6-diethoxyphenyl group, 5-bromo-2,6-di-i-propoxyphenyl Group, 5-bromo-2-methylcarbonyloxyphenyl group, 5-bromo-2-ethylcarbonyloxyphenyl group, 5-bromo-2-n-propylcarbonyloxyphenyl group, 5-bromo 2-i-propylcarbonyloxyphenyl group, 5-bromo-2-n-butylcarbonyloxyphenyl group, 5-bromo-2-i-butylcarbonyloxyphenyl group, 5-bromo-2-s-butylcarbonyloxy Phenyl group, 5-bromo-2-t-butylcarbonyloxyphenyl group, 5-bromo-2-benzyloxyphenyl group,
5-iodo-phenyl group, 5-iodo-2-methylphenyl group, 5-iodo-2-trifluoromethylphenyl group, 5-iodo-3-methylphenyl group, 5-iodo-4-methylphenyl group, 5 -Iodo-2-ethylphenyl group, 5-iodo-2-pentafluoroethylphenyl group, 5-iodo-2-n-propylphenyl group, 5-iodo-2-i-propylphenyl group, 5-iodo-2 -Heptafluoro-n-propylphenyl group, 5-iodo-2-heptafluoro-i-propylphenyl group, 5-iodo-2-n-butylphenyl group, 5-iodo-2-i-butylphenyl group, 5 -Iodo-2-s-butylphenyl group, 5-iodo-2-t-butylphenyl group, 5-iodo-2-nonafluoro-n-butylphenyl group, 5-iodo-2- Nafluoro-t-butylphenyl group, 5-iodo-2,6-dimethylphenyl group, 5-iodo-2,6-ditrifluoromethylphenyl group, 5-iodo-2,6-diethylphenyl group, 5-iodo- 2,6-dipentafluoroethylphenyl group, 5-iodo-2-methoxyphenyl group, 5-iodo-3-methoxyphenyl group, 5-iodo-4-methoxyphenyl group, 5-iodo-2-ethoxyphenyl group 5-iodo-3-ethoxyphenyl group, 5-iodo-4-ethoxyphenyl group, 5-iodo-2-i-propoxyphenyl group, 5-iodo-3-i-propoxyphenyl group,
5-iodo-4-i-propoxyphenyl group, 5-iodo-2-n-butoxyphenyl group, 5-iodo-2-i-butoxyphenyl group, 5-iodo-2-s-butoxyphenyl group, 5- Iodo-2-t-butoxyphenyl group, 5-iodo-3-n-butoxyphenyl group, 5-iodo-3-i-butoxyphenyl group, 5-iodo-3-s-butoxyphenyl group, 5-iodo- 3-t-butoxyphenyl group, 5-iodo-4-n-butoxyphenyl group, 5-iodo-4-i-butoxyphenyl group, 5-iodo-4-s-butoxyphenyl group, 5-iodo-4- t-butoxyphenyl group, 5-iodo-2,6-dimethoxyphenyl group, 5-iodo-2,6-diethoxyphenyl group, 5-iodo-2,6-di-i-propoxyphenyl group, 5-iodo 2-methylcarbonyloxyphenyl group, 5-iodo-2-ethylcarbonyloxyphenyl group, 5-iodo-2-n-propylcarbonyloxyphenyl group, 5-iodo-2-i-propylcarbonyloxyphenyl group, 5- Iodo-2-n-butylcarbonyloxyphenyl group, 5-iodo-2-i-butylcarbonyloxyphenyl group, 5-iodo-2-s-butylcarbonyloxyphenyl group, 5-iodo-2-t-butylcarbonyl An oxyphenyl group, a 5-iodo-2-benzyloxyphenyl group,
2-biphenylyl group, 3-biphenylyl group, 4-biphenylyl group,
1-naphthyl group, 2-naphthyl group, 2-methyl-1-naphthyl group, 2-trifluoromethyl-1-naphthyl group, 2-ethyl-1-naphthyl group, 2-pentafluoroethyl-1-naphthyl group, 2-n-propyl-1-naphthyl group, 2-i-propyl-1-naphthyl group, 2-pentafluoro-n-propyl-1-naphthyl group, 2-heptafluoro-i-propyl-1-naphthyl group, 2-n-butyl-1-naphthyl group, 2-i-butyl-1-naphthyl group, 2-s-butyl-1-naphthyl group, 2-t-butyl-1-naphthyl group, 2-nonafluoro-n- Butyl-1-naphthyl group, 2-nonafluoro-t-butyl-1-naphthyl group, 2-methoxy-1-naphthyl group, 2-ethoxy-1-naphthyl group, 2-i-propoxy-1-naphthyl group, 2 -N-but Ci-1-naphthyl group, 2-i-butoxy-1-naphthyl group, 2-s-butoxy-1-naphthyl group, 2-t-butoxy-1-naphthyl group, 2-methylcarbonyloxy-1-naphthyl group 2-ethylcarbonyloxy-1-naphthyl group, 2-n-propylcarbonyloxy-1-naphthyl group, 2-i-propylcarbonyloxy-1-naphthyl group, 2-n-butylcarbonyloxy-1-naphthyl group 2-i-butylcarbonyloxy-1-naphthyl group, 2-s-butylcarbonyloxy-1-naphthyl group, 2-t-butylcarbonyloxy-1-naphthyl group, 2-phenyl-1-naphthyl group, 2 -(2-Fluorophenyl) -1-naphthyl group, 2- (2-chlorophenyl) -1-naphthyl group, 2- (2-bromophenyl) -1-naphthyl group 2- (2-iodophenyl) -1-naphthyl group, 2- (2-methylphenyl) -1-naphthyl group, 2- (2-methylphenyl) -1-naphthyl group, 2- (3-methylphenyl) -1-naphthyl group, 2- (4-methylphenyl) -1-naphthyl group, 2- (3,5-dimethylphenyl) -1-naphthyl group, 2- (2-methoxyphenyl) -1-naphthyl group, 2- (3-methoxyphenyl) -1-naphthyl group, 2- (4-methoxyphenyl) -1-naphthyl group, 2- (3,5-dimethoxyphenyl) -1-naphthyl group, 2- (o-biphenylyl) ) -1-naphthyl group, 2- (m-biphenylyl) -1-naphthyl group, 2- (p-biphenylyl) -1-naphthyl group, 2- [p- (t-butyldimethylsilyl) phenyl] -1- Naphthyl group, 2-benzylo A xyl-1-naphthyl group,
6-bromo-1-naphthyl group, 6-bromo-2-naphthyl group, 6-bromo-2-methyl-1-naphthyl group, 6-bromo-2-trifluoromethyl-1-naphthyl group, 6-bromo- 2-ethyl-1-naphthyl group, 6-bromo-2-pentafluoroethyl-1-naphthyl group, 6-bromo-2-n-propyl-1-naphthyl group, 6-bromo-2-i-propyl-1 -Naphthyl group, 6-bromo-2-heptafluoro-n-propyl-1-naphthyl group, 6-bromo-2-heptafluoro-i-propyl-1-naphthyl group, 6-bromo-2-n-butyl- 1-naphthyl group, 6-bromo-2-i-butyl-1-naphthyl group, 6-bromo-2-s-butyl-1-naphthyl group, 6-bromo-2-t-butyl-1-naphthyl group, 6-Bromo-2-nonafluoro-n Butyl-1-naphthyl group, 6-bromo-2-nonafluoro-t-butyl-1-naphthyl group, 6-bromo-2-methoxy-1-naphthyl group, 6-bromo-2-ethoxy-1-naphthyl group, 6-bromo-2-i-propoxy-1-naphthyl group, 6-bromo-2-n-butoxy-1-naphthyl group, 6-bromo-2-i-butoxy-1-naphthyl group, 6-bromo-2 -S-butoxy-1-naphthyl group, 6-bromo-2-t-butoxy-1-naphthyl group, 6-bromo-2-methylcarbonyloxy-1-naphthyl group, 6-bromo-2-ethylcarbonyloxy- 1-naphthyl group, 6-bromo-2-n-propylcarbonyloxy-1-naphthyl group, 6-bromo-2-i-propylcarbonyloxy-1-naphthyl group, 6-bromo-2-n-butylcarboxyl Nyloxy-1-naphthyl group, 6-bromo-2-i-butylcarbonyloxy-1-naphthyl group, 6-bromo-2-s-butylcarbonyloxy-1-naphthyl group, 6-bromo-2-t-butyl Carbonyloxy-1-naphthyl group, 6-bromo-2-phenyl-1-naphthyl group, 6-bromo-2- (3-bromophenyl) -1-naphthyl group, 6-bromo-2- [2-methylphenyl ] -1-naphthyl group, 6-bromo-2- (3-methylphenyl) -1-naphthyl group, 6-bromo-2- (4-methylphenyl) -1-naphthyl group, 6-bromo-2- ( 3,5-dimethylphenyl) -1-naphthyl group, 6-bromo-2- (2-methoxyphenyl) -1-naphthyl group, 6-bromo-2- (3-methoxyphenyl) -1-naphthyl group, 6 -Bromo-2 -(4-methoxyphenyl) -1-naphthyl group, 6-bromo-2- (3,5-dimethoxyphenyl) -1-naphthyl group, 6-bromo-2- (o-biphenylyl) -1-naphthyl group, 6-bromo-2- (m-biphenylyl) -1-naphthyl group, 6-bromo-2- (p-biphenylyl) -1-naphthyl group, 6-bromo-2- [p- (t-butyldimethylsilyl) Phenyl] -1-naphthyl group, 6-bromo-2-benzyloxy-1-naphthyl group,
6-iodo-1-naphthyl group, 6-iodo-2-naphthyl group, 6-iodo-2-methyl-1-naphthyl group, 6-iodo-2-trifluoromethyl-1-naphthyl group, 6-iodo- 2-ethyl-1-naphthyl group, 6-iodo-2-pentafluoroethyl-1-naphthyl group, 6-iodo-2-n-propyl-1-naphthyl group, 6-iodo-2-i-propyl-1 -Naphthyl group, 6-iodo-2-heptafluoro-n-propyl-1-naphthyl group, 6-iodo-2-heptafluoro-i-propyl-1-naphthyl group, 6-iodo-2-n-butyl- 1-naphthyl group, 6-iodo-2-i-butyl-1-naphthyl group, 6-iodo-2-s-butyl-1-naphthyl group, 6-iodo-2-t-butyl-1-naphthyl group, 6-iodo-2-nonafluoro-n Butyl-1-naphthyl group, 6-iodo-2-nonafluoro-t-butyl-1-naphthyl group, 6-iodo-2-methoxy-1-naphthyl group, 6-iodo-2-ethoxy-1-naphthyl group, 6-iodo-2-i-propoxy-1-naphthyl group, 6-iodo-2-n-butoxy-1-naphthyl group, 6-iodo-2-i-butoxy-1-naphthyl group, 6-iodo-2 -S-butoxy-1-naphthyl group, 6-iodo-2-t-butoxy-1-naphthyl group, 6-iodo-2-methylcarbonyloxy-1-naphthyl group, 6-iodo-2-ethylcarbonyloxy- 1-naphthyl group, 6-iodo-2-n-propylcarbonyloxy-1-naphthyl group, 6-iodo-2-i-propylcarbonyloxy-1-naphthyl group, 6-iodo-2-n-butylcarboxyl Nyloxy-1-naphthyl group, 6-iodo-2-i-butylcarbonyloxy-1-naphthyl group, 6-iodo-2-s-butylcarbonyloxy-1-naphthyl group, 6-iodo-2-t-butyl Carbonyloxy-1-naphthyl group, 6-iodo-2-phenyl-1-naphthyl group, 6-iodo-2- (3-bromophenyl) -1-naphthyl group, 6-iodo-2- (2-methylphenyl) ) -1-naphthyl group, 6-iodo-2- (3-methylphenyl) -1-naphthyl group, 6-iodo-2- (4-methylphenyl) -1-naphthyl group, 6-iodo-2- ( 3,5-dimethylphenyl) -1-naphthyl group, 6-iodo-2- (2-methoxyphenyl) -1-naphthyl group, 6-iodo-2- (3-methoxyphenyl) -1-naphthyl group, 6 -Iodo-2 -(4-methoxyphenyl) -1-naphthyl group, 6-iodo-2- (3,5-dimethoxyphenyl) -1-naphthyl group, 6-iodo-2- (o-biphenylyl) -1-naphthyl group, 6-iodo-2- (m-biphenylyl) -1-naphthyl group, 6-iodo-2- (p-biphenylyl) -1-naphthyl group, 6-iodo-2- [p- (t-butyldimethylsilyl) Phenyl] -1-naphthyl group, 6-iodo-2-benzyloxy-1-naphthyl group, and the like.

Preferred R ¹ in the formulas (1) and (2) is a hydrogen atom, a phenyl group (the phenyl group is unsubstituted, a C _1-4 alkyl group, a C _1-4 haloalkyl group, C _1-4 alkoxy group, C _1-4 alkylcarbonyloxy group, C _6-12 aryl group (the aryl group is unsubstituted or C _1-4 alkyl group, C _1-4 haloalkyl group and C ₁ Substituted with one or more substituents selected from the same or different _-4 alkoxy groups.), C _6-22 arylmethyloxy groups (the arylmethyloxy groups are unsubstituted or C _{1 -4} alkyl group, C _1-4 alkoxy group, one or more substituents selected from the same or different substituents selected from a halogen atom and a phenyl group. A naphthyl group (the naphthyl group). Butyl group is unsubstituted, or a C _1-4 alkyl group, C _1-4 haloalkyl group, C _1-4 alkoxy, C _1-4 alkylcarbonyloxy group, C _6-12 aryl group (said aryl The group is unsubstituted or substituted with one or more substituents which are the same or different and are selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group. , T-butyldimethylsilyl group, C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or C _1-4 alkyl group, C _1-4 alkoxy group, halogen atom and phenyl group) Substituted with one or more substituents selected from the same or different from each other) and one or more substituents selected from halogen atoms, and are optically active or optically inactive. .)

Preferred R ¹ in the above formulas (1) and (2) is a hydrogen atom, a phenyl group, a 2-trifluoromethylphenyl group, a 2-pentafluoroethylphenyl group, a 2-benzyloxyphenyl group, 2- (2 -Methylbenzyloxy) phenyl group, 2- (3-methylbenzyloxy) phenyl group, 2- (4-methylbenzyloxy) phenyl group, 2- (2,4,6-tri-i-propylbenzyloxy) phenyl Group, 2- (2-fluorobenzyloxy) phenyl group, 2- (3-fluorobenzyloxy) phenyl group, 2- (4-fluorobenzyloxy) phenyl group, 2- (2-bromobenzyloxy) phenyl group, 2- (3-bromobenzyloxy) phenyl group, 2- (4-bromobenzyloxy) phenyl group, 2- (2-methoxybenzyloxy) Enyl group, 2- (3-methoxybenzyloxy) phenyl group, 2- (4-methoxybenzyloxy) phenyl group, 2-methoxyphenyl group, 2- (9-anthrylmethoxy) phenyl group, 2- (1- Pyrenylmethoxy) phenyl group, 2-mesitylmethoxyphenyl group, 2- (2-naphthylmethoxy) phenyl group, 2- (2-biphenylylmethoxy) phenyl group, 2-ethoxyphenyl group, 2-i-propoxyphenyl group, 2-n-butoxyphenyl group, 2-phenyl-1-naphthyl group, 2-methoxy-1-naphthyl group.

More preferable R ¹ in the above formulas (1) and (2) is a hydrogen atom, 2-trifluoromethylphenyl group, 2-benzyloxyphenyl group, 2- (4-methylbenzyloxy) phenyl group, 2- (2,4,6-tri-i-propylbenzyloxy) phenyl group, 2- (2-fluorobenzyloxy) phenyl group, 2- (2-bromobenzyloxy) phenyl group, 2- (2-methoxybenzyloxy) ) Phenyl group, 2-methoxyphenyl group, 2- (9-anthrylmethoxy) phenyl group, 2-mesitylmethoxyphenyl group, 2- (2-naphthylmethoxy) phenyl group, 2- (2-biphenylylmethoxy) A phenyl group, a 2-phenyl-1-naphthyl group, and a 2-methoxy-1-naphthyl group;

R ² in the formulas (1) and (2) is a hydrogen atom, a halogen atom, a C _1-4 alkyl group or a C _1-4 haloalkyl group.

R ² in Formula (1) and Formula (2) will be specifically described. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Examples of the C _1-4 alkyl group include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, an s-butyl group, and a t-butyl group. The C _1-4 haloalkyl group is a fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, chlorofluoromethyl group, dichloromethyl group, bromofluoromethyl group, trifluoromethyl group, chlorodifluoromethyl group. Dichlorofluoromethyl group, trichloromethyl group, bromodifluoromethyl group, bromochlorofluoromethyl group, dibromofluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2-chloro-2-fluoroethyl group, 2,2-dichloroethyl group, 2-bromo-2-fluoroethyl group, 2,2,2-trifluoroethyl group, 2-chloro-2,2-difluoroethyl group 2,2-dichloro-2-fluoroethyl group, 2,2,2-tri Chloroethyl group, 2-bromo-2,2-difluoroethyl group, 2-bromo-2-chloro-2-fluoroethyl group, 2-bromo-2,2-dichloroethyl group, 1,1,2,2-tetra Fluoroethyl group, pentafluoroethyl group, 1-chloro-1,2,2,2-tetrafluoroethyl group, 2-chloro-1,1,2,2-tetrafluoroethyl group, 1,2-dichloro-1 , 2,2-trifluoroethyl group, 2-bromo-1,1,2,2-tetrafluoroethyl group, 2-fluoropropyl group, 2-chloropropyl group, 2-bromopropyl group, 2-chloro-2 -Fluoropropyl group, 2,3-dichloropropyl group, 2-bromo-3-fluoropropyl group, 3-bromo-2-chloropropyl group, 2,3-dibromopropyl group, 3,3,3-trifluoro Lopyl group, 3-bromo-3,3-difluoropropyl group, 2,2,3,3-tetrafluoropropyl group, 2-chloro-3,3,3-trifluoropropyl group, 2,2,3,3 , 3-pentafluoropropyl group, 1,1,2,3,3,3-hexafluoropropyl group, heptafluoropropyl group, 2,3-dichloro-1,1,2,3,3-pentafluoropropyl group 2-fluoro-1-methylethyl group, 2-chloro-1-methylethyl group, 2-bromo-1-methylethyl group, 2,2,2-trifluoro-1- (trifluoromethyl) ethyl group, 1,2,2,2-tetrafluoro-1- (trifluoromethyl) ethyl group, 2,2,3,3,4,4-hexafluorobutyl group, 2,2,3,4,4,4- Hexafluorobutyl group, 2,2,3 , 4,4,4-heptafluorobutyl group, 1,1,2,2,3,3,4,4-octafluorobutyl group, nonafluorobutyl group, 4-chloro-1,1,2,2, 3,3,4,4-octafluorobutyl group, 2-fluoro-2-methylpropyl group, 2-chloro-1,1-dimethylethyl group, 2-bromo-1,1-dimethylethyl group and the like can be mentioned. .

Preferred R ² in the formula (1) and the formula (2) is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a yo atom, a methyl group, urine, an ethyl group, an n-propyl group, an i-propyl group, n-butyl group, t-butyl group, fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, chlorofluoromethyl group, trifluoromethyl group, chlorodifluoromethyl group, dichlorofluoromethyl group, bromodifluoro Methyl group, bromochlorofluoromethyl group, dibromofluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2-chloro-2-fluoroethyl group, 2- Bromo-2-fluoroethyl group, 2,2,2-trifluoroethyl group, 2-chloro-2,2-difluoro Til group, 2,2-dichloro-2-fluoroethyl group, 2-bromo-2,2-difluoroethyl group, 2-bromo-2-chloro-2-fluoroethyl group, 1,1,2,2-tetra A fluoroethyl group and a pentafluoroethyl group;

More preferable R ² in the formula (1) and the formula (2) is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, an i-propyl group, a t-butyl group, A fluoromethyl group and a pentafluoroethyl group;

R ³ and R ⁴ in the formulas (1) and (2) are each independently a hydrogen atom, a halogen atom, a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, C _{A 6-12} aryl group, a C _6-12 aryloxy group, a nitro group or a cyano group;

R ³ and R ⁴ in the formulas (1) and (2) will be specifically described. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Examples of the C _1-4 alkyl group include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, an s-butyl group, and a t-butyl group. The C _1-4 haloalkyl group is a fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, chlorofluoromethyl group, dichloromethyl group, bromofluoromethyl group, trifluoromethyl group, chlorodifluoromethyl group. Dichlorofluoromethyl group, trichloromethyl group, bromodifluoromethyl group, bromochlorofluoromethyl group, dibromofluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2-chloro-2-fluoroethyl group, 2,2-dichloroethyl group, 2-bromo-2-fluoroethyl group, 2,2,2-trifluoroethyl group, 2-chloro-2,2-difluoroethyl group 2,2-dichloro-2-fluoroethyl group, 2,2,2-tri Chloroethyl group, 2-bromo-2,2-difluoroethyl group, 2-bromo-2-chloro-2-fluoroethyl group, 2-bromo-2,2-dichloroethyl group, 1,1,2,2-tetra Fluoroethyl group, pentafluoroethyl group, 1-chloro-1,2,2,2-tetrafluoroethyl group, 2-chloro-1,1,2,2-tetrafluoroethyl group, 1,2-dichloro-1 , 2,2-trifluoroethyl group, 2-bromo-1,1,2,2-tetrafluoroethyl group, 2-fluoropropyl group, 2-chloropropyl group, 2-bromopropyl group, 2-chloro-2 -Fluoropropyl group, 2,3-dichloropropyl group, 2-bromo-3-fluoropropyl group, 3-bromo-2-chloropropyl group, 2,3-dibromopropyl group, 3,3,3-trifluoro Lopyl group, 3-bromo-3,3-difluoropropyl group, 2,2,3,3-tetrafluoropropyl group, 2-chloro-3,3,3-trifluoropropyl group, 2,2,3,3 , 3-pentafluoropropyl group, 1,1,2,3,3,3-hexafluoropropyl group, heptafluoropropyl group, 2,3-dichloro-1,1,2,3,3-pentafluoropropyl group 2-fluoro-1-methylethyl group, 2-chloro-1-methylethyl group, 2-bromo-1-methylethyl group, 2,2,2-trifluoro-1- (trifluoromethyl) ethyl group, 1,2,2,2-tetrafluoro-1- (trifluoromethyl) ethyl group, 2,2,3,3,4,4-hexafluorobutyl group, 2,2,3,4,4,4- Hexafluorobutyl group, 2,2,3,3 4,4,4-heptafluorobutyl group, 1,1,2,2,3,3,4,4-octafluorobutyl group, nonafluorobutyl group, 4-chloro-1,1,2,2,3 , 3,4,4-octafluorobutyl group, 2-fluoro-2-methylpropyl group, 2-chloro-1,1-dimethylethyl group, 2-bromo-1,1-dimethylethyl group, and the like. Examples of the C _1-4 alkoxy group include methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butoxy group, i-butoxy group, s-butoxy group, t-butoxy group and the like. Examples of the C _6-12 aryl group include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 2-biphenylyl group, a 3-biphenylyl group, and a 4-biphenylyl group. Examples of the C _6-12 aryloxy group include phenyloxy group, 1-naphthyloxy group, 2-naphthyloxy group, 2-biphenylyloxy group, 3-biphenylyloxy group, 4-biphenylyloxy group and the like. It is done.

Preferred R ³ and R ⁴ in the formulas (1) and (2) are a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n- Butyl group, i-butyl group, s-butyl group, t-butyl group, trifluoromethyl group, pentafluoroethyl group, methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butoxy group, i -Butoxy group, s-butoxy group, t-butoxy group, phenyl group, 1-naphthyl group, 2-naphthyl group, phenyloxy group.

More preferable R ³ and R ⁴ in the above formulas (1) and (2) are hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, i-propyl group, t-butyl. Group, trifluoromethyl group, methoxy group, ethoxy group, i-propoxy group and t-butoxy group.

Specific examples of R ⁵ and R ^{7 in} the case where R ² and R ^{3 in the} formulas (1) and (2) together form —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ — The description is the same as R ³ and R ⁴ described above. Moiety ^{-CR 5 = CR 6 -CR 7 =} CR 8 - -CR 5 = the partial structure corresponds to R ^2, the partial structure -CR ⁸ = corresponds to R ^3.

The specific explanation of R ⁶ when R ² and R ^{3 in the} formulas (1) and (2) together form —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ — The same as R ² described above.

In the formula (1) and the formula (2), when R ² and R ³ are combined to form —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ —, R ⁸ is a hydrogen atom, A halogen atom, and specific examples of R ⁶ include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. R ⁸ is preferably a hydrogen atom or a fluorine atom.

Preferred R ⁵ and R ⁷ when R ² and R ^{3 in the} formulas (1) and (2) are combined to form —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ — Each independently a hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, i-propyl group, t-butyl group, trifluoromethyl group, methoxy group, ethoxy group, i-propoxy group Or a t-butoxy group, and preferred R ⁶ is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, an i-propyl group, a t-butyl group, a trifluoromethyl group or a penta It is a fluoroethyl group.

から選ばれる構造に、Ｒ¹、Ｒ²、Ｒ³及びＲ⁴のうち３つがそれぞれ独立に置換基Ａを表す式（１）で表される部分構造が、Ｒ¹、Ｒ²、Ｒ³及びＲ⁴のいずれかの位置で２ないし３個結合した構造を持つ多核のフェノール化合物が好ましい。結合するフェニル基の結合位置は、それぞれ同一でも相異なっていてもよい。式（ｉ）中のｍは、２又は３の整数である。R ¹ , R ² , R ^3, and R ⁴ are each independently 1 to 3 phenyl groups (the phenyl group is unsubstituted, or is the same or different one or more selected from substituent A and hydroxy group) is substituted with a substituent.) substituted by further C _1-4 alkyl groups and the same or different by one or more, optionally substituted with a substituent C _1-4 alkyl group selected from halogen atoms Phenyl substituted by 1 to 3 phenyl groups (the phenyl group is unsubstituted or substituted by one or more substituents selected from substituent A and hydroxy group). A group, a phenylcarbonyl group (the phenylcarbonyl group is unsubstituted or substituted with one or more substituents selected from the substituent A and a hydroxy group), a phenylsulfonyl group ( When the phenylsulfonyl group is unsubstituted or may be substituted with one or more substituents selected from the substituent A and a hydroxy group, the preferred structure is represented by the following formula: (I), (ii), (iii), (iv), (v) and (vi)

A partial structure represented by the formula (1) in which three of R ¹ , R ² , R ³ and R ⁴ each independently represent a substituent A is R ¹ , R ² , R ³ and A polynuclear phenol compound having a structure in which 2 to 3 bonds are bonded at any position of R ⁴ is preferred. The bonding positions of the phenyl groups to be bonded may be the same or different. M in the formula (i) is an integer of 2 or 3.

  Among the formulas (i), (ii), (iii), (iv), (v) and (vi), for example, the structures represented by the formulas (i), (ii) and (iii) are more preferable. . M in the formula (i) is preferably 2.

Examples of R ¹¹ in formula (i) include a hydrogen atom, a halogen atom, a C _1-4 alkyl group, or a C _1-4 haloalkyl group.

R ¹¹ in the formula (i) will be specifically described. Examples of the C _1-4 alkyl group include a methyl group, an ethyl group, an n-propyl group, and an n-butyl group. Examples of the C _1-4 haloalkyl group include a fluoromethyl group, a chloromethyl group, a bromomethyl group, an iodomethyl group, a trifluoromethyl group, and a pentafluoroethyl group.
Preferred R ¹¹ in the formula (i) is hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, trifluoro group. A methyl group and a pentafluoroethyl group;
More preferable R ¹¹ in the formula (i) is a hydrogen atom, a fluorine atom, a methyl group or a trifluoromethyl group.

Next, each substituent in the said formula (a) showing the amine compound used as a multidentate ligand is demonstrated.
R ⁹ in the formula (a) is a C _1-3 alkyl group, or two R ⁹ on the same nitrogen atom together are ═CH—R ¹⁰ .
R ⁹ in the formula (a) will be specifically described. Examples of the C _1-3 alkyl group include a methyl group, an ethyl group, an n-propyl group, and an i-propyl group.
Preferable R ⁹ in the formula (a) is a methyl group or an ethyl group.

When two R ⁹ on the same nitrogen atom in the formula (a) are ═CH—R ¹⁰ together, R ¹⁰ is a C _6-12 aryl group (the aryl group is unsubstituted) Or substituted with one or more substituents which are the same or different and are selected from a halogen atom, a C _1-4 alkyl group and a C _1-4 alkoxy group.

R ¹⁰ in the case where two R ⁹ on the same nitrogen atom in the formula (a) are together ═CH—R ¹⁰ will be specifically described. The C _6-12 aryl group is a phenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-bromophenyl group. 3-bromophenyl group, 4-bromophenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2-ethylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group, 2 -N-propylphenyl group, 2-i-propylphenyl group, 2-n-butylphenyl group, 2-i-butylphenyl group, 2-s-butylphenyl group, 2-t-butylphenyl group, 2,6 -Dimethylphenyl group, 2,6-dipropylmethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, -Ethoxyphenyl group, 3-ethoxyphenyl group, 4-ethoxyphenyl group, 2-n-propoxyphenyl group, 2-i-propoxyphenyl group, 2-n-butoxyphenyl group, 2-i-butoxyphenyl group, 2 -S-butoxyphenyl group, 2-t-butoxyphenyl group, 2,6-dimethoxyphenyl group, 2,6-dipropoxymethoxyphenyl group, 1-naphthyl group, 2-naphthyl group, o-biphenylyl group, m- Biphenylyl group, p-biphenylyl group and the like can be mentioned.

The preferred R ¹⁰ when two R ⁹ on the same nitrogen atom in the formula (a) is a = CH-R ¹⁰ taken together are phenyl, 2-fluorophenyl group, 2-bromophenyl group, A 2-methylphenyl group, a 2-ethylphenyl group, a 2-methoxyphenyl group, and a 2-i-propoxyphenyl group;
More preferred R ¹⁰ is a phenyl group, 2-fluorophenyl group, 2-methylphenyl group when two R ⁹ on the same nitrogen atom in the formula (a) is a = CH-R ¹⁰ taken together 2-methoxyphenyl group and 2-i-propoxyphenyl group.
Preferred amine compounds represented by the formula (a) are N, N, N ′, N′-tetramethylethylenediamine, N, N, N ′, N ″, N ″ -pentamethyldiethylenetriamine, and more A preferred amine compound is N, N, N ′, N′-tetramethylethylenediamine.

  Many of the amine compounds that are polydentate ligands represented by the formula (a) are available as reagents. Moreover, about the amine compound which is not marketed, the example which can be manufactured with the method shown below is shown.

For amine compounds of formula (a) where n = 2, J. et al Org. Chem. (1987), 52, 2571-2576. It can be produced according to the method described on page 2574. (Reaction Formula 1) is shown below.

For synthesis examples of amine compounds in which two R ⁹ on the same nitrogen atom of formula (a) are taken together to represent ═CH—R ¹⁰ , see Tetrahedron Letters (1990), 31, 451-454. It can be produced according to the method described on page 452. (Reaction formula 2) is shown below.

  The conventional method 11 described above is a method for producing an aldehyde compound from a hydroxyaryl compound by using paraformaldehyde and reacting with a combination of magnesium chloride and triethylamine (Non-patent Documents 17 and 18). This is a reaction in which a hydroxyaryl aldehyde compound can be efficiently and regioselectively introduced with a formyl group. Organic Synthesis, (2005), 82, 64-67. Describes that it only gives a formylated hydroxyaryl compound at the ortho position, but not a bisformylated compound. As a result of further investigation by the present inventors, a bisformylated compound reacted as described. It was confirmed not to generate. However, it was found that a by-product with an unknown structure was formed.

  When this was further examined, it was found that this by-product can be suppressed by replacing the amine used for the reaction with an amine compound that becomes a multidentate ligand. A comparative example is described in the following example description part.

  The operation of the production method when the 2-hydroxyarylaldehyde compound is mononuclear will be described. After replacing the flask equipped with a stirrer and a reflux tube with nitrogen, 1 to 4 mol (preferably 1.5 to 3 mol) of magnesium chloride and 1 to 8 mol of paraformaldehyde with respect to the starting hydroxyaryl compound. (1.5 to 4 mol is preferred) and an organic solvent (the concentration is not particularly limited, but 0.05 to 2.0 mol / L is preferred) and stirred. The organic solvent used in the reaction is preferably a nitrile solvent, an ether solvent, or dimethyl sulfoxide. Examples of the nitrile solvent include acetonitrile, propionitrile, butyronitrile, isobutyronitrile, and acetonitrile and propionitrile are preferable. Examples of the ether solvent include dioxane, t-butyl methyl ether, c-pentyl methyl ether, tetrahydrofuran, and diethyl ether, and dioxane and tetrahydrofuran are preferable. The temperature of the reaction solution at this stage is not particularly limited, but is from the solvent freezing point temperature to the solvent boiling point temperature, preferably 15 to 120 ° C.

  Next, 0.1 to 4 mol (preferably 0.2 to 3 mol) of an amine compound is added to hydroxyaryl as a starting material, and the organic solvent (the type of the organic solvent is described above) is added. A solution of the starting hydroxyaryl (1 mole) dissolved or suspended is added into the reaction solution. The starting material hydroxyaryl itself can also be added to the reaction solution. The reaction temperature is preferably 55 to 120 ° C, more preferably 60 to 100 ° C. The reaction time is not particularly limited, and is appropriately selected by examining the reaction conversion rate. After completion of the reaction, the reaction mixture is cooled to 10 to 30 ° C., quenched with diluted hydrochloric acid prepared to 1 to 4 mol / L, subjected to liquid separation operation and re-extraction, and the solvent is distilled off to obtain a crude product. .

  The purification method of the crude product is not particularly limited, and is appropriately selected depending on the target 2-hydroxyaryl aldehyde compound. Purification methods include sublimation purification, column chromatography purification, purification by crystallization operation-filtration operation, and the like.

  The operation of the production method when the 2-hydroxyaryl aldehyde compound is polynuclear will be described. The amount of the reaction reagent to be used is prepared according to the number of phenolic hydroxyl groups in the starting material. In the case of a binuclear hydroxyaryl compound, 2 to 8 mol (preferably 3 to 6 mol) of magnesium chloride and 2 to 16 mol (preferably 3 to 8 mol) of paraformaldehyde are used with respect to the starting hydroxyaryl compound. And 0.2 to 8 mol (preferably 0.4 to 6 mol) of the amine compound. In the case of the trinuclear hydroxyaryl compound, 3 to 12 mol (preferably 4.5 to 9 mol) of magnesium chloride and 3 to 24 mol (4.5 to 4.5 mol) of paraformaldehyde are used with respect to the starting hydroxyaryl compound. 12 mol is preferable), and the amine compound is 0.3 to 12 mol (preferably 0.6 to 9 mol). About other operation, it is the same as operation of the manufacturing method of said mononuclear 2-hydroxyaryl aldehyde compound.

  Hereinafter, although an Example demonstrates in more detail, this invention is not limited to these.

(Synthesis of starting material hydroxyaryl compound)
The synthesis of 2 ′-(phenylmethoxy) -1,1′-biphenyl-2-ol (5) is described in Organic & Biomolecular Chemistry (2006), 4 (19), 3639-3647. It can be produced according to the method described. The synthesis method is shown in (Reaction Scheme 3).

The synthesis of 2′-methoxy-1,1′-biphenyl-2-ol (8) is described in Tetrahedron Letters (2002), 43, 9327-9329. It can be produced according to the method described. The synthesis method is shown in (Reaction Scheme 4).

撹拌機器と還流管を備えたフラスコを窒素置換した後、塩化マグネシウム（０．６９ｇ，７．２ｍｍｏｌ）を、パラホルムアルデヒド（０．３３ｇ，１１ｍｍｏｌ）を、テトラヒドロフラン（１０ｍＬ）を加え、２６〜３０℃にて撹拌した。
次にアミン化合物であるＮ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン（０．８４ｇ，７．２ｍｍｏｌ）を加え、テトラヒドロフラン（１．１ｍＬ）に溶解させたヒドロキシアリール化合物（５）（１．０ｇ，３．６ｍｍｏｌ）の溶液を、反応溶液中に加えた。反応温度を６４〜６６℃にて、２１時間撹拌し反応を行った。反応終了後は、１５〜２０℃に冷却し、２．５ｍｏｌ／Ｌに調製した希釈塩酸を用いて反応をクエンチして、有機層を分液し、テトラヒドロフランにて再抽出した有機層と合わせ、溶媒留去し粗生成物を得た。次にカラムクロマトグラフィーを用いて精製し、目的化合物の２−ヒドロキシアリールアルデヒド化合物（９）（０．８８ｇ，収率８０％，化学純度９９．５％）を淡黄色オイル状で得た。
ＨＰＬＣ分析条件：
カラム名 Ｇｅｍｉｎｉ ５ｕ Ｃ１８ １１０Ａ （ｐｈｅｎｏｍｅｎｅｘ社製），
溶離液 アセトニトリル／水／酢酸＝６００／４００／１（ｖ／ｖ／ｖ），
流量 １．０ｍＬ／ｍｉｎ，カラム温度 ４０℃，測定波長 ２３０ｎｍ．
¹Ｈ−ＮＭＲ（３００ＭＨｚ，ＣＤＣｌ₃）δ；５．０８（ｓ，２Ｈ，―ＣＨ₂―），７．０２〜７．０９（ｍ，３Ｈ，Ａｒ），７．２１〜７．３７（ｍ，７Ｈ，Ａｒ），７．５４〜７．５９（ｍ，２Ｈ，Ａｒ），９．９４（ｓ，１Ｈ，ＣＨＯ），１１．３６（ｓ，１Ｈ，ＯＨ）．(Synthesis of hydroxyaryl aldehyde compounds)
Example 1
A synthesis method of 2-hydroxy-2 ′-(phenylmethoxy) -1,1′-biphenyl-3-carbaldehyde (9) and (Scheme 5) are shown below.

A flask equipped with a stirrer and a reflux tube was purged with nitrogen, and then magnesium chloride (0.69 g, 7.2 mmol), paraformaldehyde (0.33 g, 11 mmol), tetrahydrofuran (10 mL) were added, and the temperature was 26-30 ° C. Was stirred at.
Next, N, N, N ′, N′-tetramethylethylenediamine (0.84 g, 7.2 mmol) as an amine compound was added, and the hydroxyaryl compound (5) (1. 0 g, 3.6 mmol) was added into the reaction solution. The reaction was carried out by stirring for 21 hours at a reaction temperature of 64 to 66 ° C. After completion of the reaction, the reaction mixture is cooled to 15 to 20 ° C., quenched with diluted hydrochloric acid prepared to 2.5 mol / L, the organic layer is separated, combined with the organic layer re-extracted with tetrahydrofuran, The solvent was distilled off to obtain a crude product. Next, purification was performed using column chromatography to obtain the target compound 2-hydroxyarylaldehyde compound (9) (0.88 g, yield 80%, chemical purity 99.5%) as a pale yellow oil.
HPLC analysis conditions:
Column name Gemini 5u C18 110A (Phenomenex),
Eluent acetonitrile / water / acetic acid = 600/400/1 (v / v / v),
Flow rate: 1.0 mL / min, column temperature: 40 ° C., measurement wavelength: 230 nm.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.08 (s, 2H, —CH ₂ —), 7.02 to 7.09 (m, 3H, Ar), 7.21 to 7.37 (m , 7H, Ar), 7.54-7.59 (m, 2H, Ar), 9.94 (s, 1H, CHO), 11.36 (s, 1H, OH).

撹拌機器と還流管を備えたフラスコを窒素置換した後、塩化マグネシウム（２．９ｇ，３０ｍｍｏｌ）を、パラホルムアルデヒド（１．４ｇ，４５ｍｍｏｌ）を、テトラヒドロフラン（３０ｍＬ）を加え、２４〜２７℃にて撹拌した。
次にアミン化合物であるＮ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン（３．５ｇ，３０ｍｍｏｌ）を加え、テトラヒドロフラン（３．４ｍＬ）に溶解させたヒドロキシアリール化合物（８）（３．０ｇ，１５ｍｍｏｌ）の溶液を、反応溶液中に加えた。反応温度を６４〜６６℃にて、２０時間撹拌し反応を行った。反応終了後は、１５〜２０℃に冷却し、２．５ｍｏｌ／Ｌに調製した希釈塩酸を用いて反応をクエンチして、有機層を分液し、テトラヒドロフランにて再抽出した有機層と合わせ、溶媒留去し粗生成物を得た。次にカラムクロマトグラフィーを用いて精製し、目的化合物の２−ヒドロキシアリールアルデヒド化合物（１０）（２．８８ｇ，収率８４％，化学純度９７％）を淡黄色結晶で得た。
ＨＰＬＣ分析条件：
カラム名 Ｇｅｍｉｎｉ ５ｕ Ｃ１８ １１０Ａ （ｐｈｅｎｏｍｅｎｅｘ社製），
溶離液 アセトニトリル／水／酢酸＝６００／４００／１（ｖ／ｖ／ｖ），
流量 １．０ｍＬ／ｍｉｎ，カラム温度 ４０℃，測定波長 ２５４ｎｍ．
¹Ｈ−ＮＭＲ（３００ＭＨｚ，ＣＤＣｌ₃）δ；３．７９（ｓ，３Ｈ，ＯＣＨ₃），７．００〜７．１０（ｍ，３Ｈ，Ａｒ），７．２５〜７．４１（ｍ，２Ｈ，Ａｒ），７．５３〜７．５８（ｍ，２Ｈ，Ａｒ），９．９４（ｓ，１Ｈ，ＣＨＯ），１１．２９（ｓ，１Ｈ，ＯＨ）．Example 2
A synthesis method of 2-hydroxy-2′-methoxy-1,1′-biphenyl-3-carbaldehyde (10) and (Reaction Scheme 6) are shown below.

A flask equipped with a stirrer and a reflux tube was purged with nitrogen, and then magnesium chloride (2.9 g, 30 mmol), paraformaldehyde (1.4 g, 45 mmol), and tetrahydrofuran (30 mL) were added, and the temperature was 24-27 ° C. Stir.
Next, the amine compound N, N, N ′, N′-tetramethylethylenediamine (3.5 g, 30 mmol) was added, and the hydroxyaryl compound (8) (3.0 g, dissolved in tetrahydrofuran (3.4 mL)) was added. 15 mmol) was added into the reaction solution. The reaction was carried out by stirring at a reaction temperature of 64 to 66 ° C. for 20 hours. After completion of the reaction, the reaction mixture is cooled to 15 to 20 ° C., quenched with diluted hydrochloric acid prepared to 2.5 mol / L, the organic layer is separated, combined with the organic layer re-extracted with tetrahydrofuran, The solvent was distilled off to obtain a crude product. Next, purification was performed using column chromatography to obtain the target compound 2-hydroxyarylaldehyde compound (10) (2.88 g, yield 84%, chemical purity 97%) as pale yellow crystals.
HPLC analysis conditions:
Column name Gemini 5u C18 110A (Phenomenex),
Eluent acetonitrile / water / acetic acid = 600/400/1 (v / v / v),
Flow rate 1.0 mL / min, column temperature 40 ° C., measurement wavelength 254 nm.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 3.79 (s, 3H, OCH ₃ ), 7.00 to 7.10 (m, 3H, Ar), 7.25 to 7.41 (m, 2H) , Ar), 7.53 to 7.58 (m, 2H, Ar), 9.94 (s, 1H, CHO), 11.29 (s, 1H, OH).

Example 3
Synthesis Method of 2-Hydroxy-2′-methoxy-1,1′-biphenyl-3-carbaldehyde (10) After replacing a flask equipped with a stirrer and a reflux tube with nitrogen, magnesium chloride (52 g, 0.55 mol) Paraformaldehyde (25 g, 0.82 mol) was added tetrahydrofuran (495 mL), and the mixture was stirred at 63 to 66 ° C.
Next, N, N, N ′, N′-tetramethylethylenediamine (64 g, 0.55 mol) as an amine compound was added, and the hydroxyaryl compound (8) (55 g, 0.27 mol) dissolved in tetrahydrofuran (93 mL) was added. Was added to the reaction solution. The reaction was carried out by stirring for 12 hours at a reaction temperature of 64 to 66 ° C. A part of the reaction solution was sampled, and an affinity analysis of the target product 2-hydroxyarylaldehyde compound (10) was conducted by HPLC analysis to obtain a conversion rate. The results are shown in Table 1 below.
HPLC analysis conditions:
Column name L-columnODS (Chemicals Evaluation and Research Institute),
Eluent acetonitrile / water / acetic acid = 600/400/1 (v / v / v),
Flow rate: 1.0 mL / min, column temperature: 40 ° C., measurement wavelength: 230 nm.

（注１）：
原料ヒドロキシアリール化合物（８）の水酸基のオルト位の水素が、ヒドロキシメチル基になった化合物と推定される。Table 1: Results of Example 3

(Note 1):
It is presumed that the hydrogen at the ortho position of the hydroxyl group of the raw material hydroxyaryl compound (8) is a hydroxymethyl group.

Comparative Example 1
Synthesis method of 2-hydroxy-2′-methoxy-1,1′-biphenyl-3-carbaldehyde (10) The N, N, N ′, N′-tetramethylethylenediamine used in Example 3 was changed to triethylamine. It shows about the comparative example 1 performed.
A flask equipped with a stirrer and a reflux tube was purged with nitrogen, then magnesium chloride (3.8 g, 40 mmol), paraformaldehyde (1.8 g, 60 mmol), and tetrahydrofuran (40 mL) were added, and the temperature was 63 to 66 ° C. Stir.
Next, triethylamine (4.0 g, 40 mmol) as an amine compound was added, and a solution of hydroxyaryl compound (8) (4.0 g, 20 mmol) dissolved in tetrahydrofuran (5 mL) was added to the reaction solution. The reaction was carried out by stirring at a reaction temperature of 64 to 66 ° C. for 5 hours. A part of the reaction solution was sampled, and an affinity analysis of the target product 2-hydroxyarylaldehyde compound (10) was conducted by HPLC analysis to obtain a conversion rate. Table 2 below shows the results.
HPLC analysis conditions:
Column name L-columnODS (Chemicals Evaluation and Research Institute),
Eluent acetonitrile / water / acetic acid = 600/400/1 (v / v / v),
Flow rate: 1.0 mL / min, column temperature: 40 ° C., measurement wavelength: 230 nm.

（注１）：原料ヒドロキシアリール化合物（８）の水酸基のオルト位の水素が、ヒドロキシメチル基になった化合物と推定される。Table 2: Results of Comparative Example 1

(Note 1): It is presumed that the hydrogen at the ortho position of the hydroxyl group of the raw material hydroxyaryl compound (8) is a hydroxymethyl group.

撹拌機器と還流管を備えたフラスコを窒素置換した後、塩化マグネシウム（２．６ｇ，２７ｍｍｏｌ）を、パラホルムアルデヒド（１．２ｇ，３９ｍｍｏｌ）を、アセトニトリル（２０ｍＬ）を加え、２６〜３０℃にて撹拌した。
次にアミン化合物であるＮ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン（３．１ｇ，２６ｍｍｏｌ）を加え、市販品のヒドロキシアリール化合物である４，４’−（１−メチルエチリデン）ビスフェノール（１１）（１．５ｇ，６．６ｍｍｏｌ）を、反応溶液中に加えた。反応温度を７８〜８１℃にて、１８時間撹拌し反応を行った。反応液の一部をサンプリングして、ＨＰＬＣ分析により転化率は、７８％であった。反応終了後は、１５〜２０℃に冷却し、２ｍｏｌ／Ｌに調製した希釈塩酸を用いて反応をクエンチした後、ジクロロメタンを加えて有機層を分液した。水層をジクロロメタンで再抽出した有機層と合わせ、溶媒留去し粗生成物を得た。次にカラムクロマトグラフィーを用いて精製し、目的化合物の二核の２−ヒドロキシアリールアルデヒド化合物（１２）（１．４ｇ，収率７３％）を微黄透明オイル状で得た。この得られた化合物は数時間後に微黄白色固体となった。
ＨＰＬＣ分析条件：
カラム名 Ｇｅｍｉｎｉ ５ｕ Ｃ１８ １１０Ａ （ｐｈｅｎｏｍｅｎｅｘ社製），
溶離液 アセトニトリル／水／酢酸＝６００／４００／１（ｖ／ｖ／ｖ），
流量 １．０ｍＬ／ｍｉｎ，カラム温度 ４０℃，測定波長 ２３０ｎｍ．
¹Ｈ−ＮＭＲ（３００ＭＨｚ，ＣＤＣｌ₃）δ；１．７１（ｓ，６Ｈ，ＣＨ₃），６．９２（ｄ, Ｊ＝９．０Ｈｚ,２Ｈ，Ａｒ）,７．３５（ｄｄ, Ｊ＝９．０Ｈｚ,２．４Ｈｚ,２Ｈ,Ａｒ）,７．４４（ｄ, Ｊ＝２．４Ｈｚ,２Ｈ,Ａｒ），９．８６（ｓ，２Ｈ，ＣＨＯ），１０．９４（ｓ，２Ｈ，ＯＨ）．Example 4
A synthesis method of 3,3 ′-(1-methylethylidene) bis (6-hydroxybenzaldehyde) (12), which is a binuclear 2-hydroxyarylaldehyde compound, is shown in (Reaction Scheme 7).

A flask equipped with a stirrer and a reflux tube was purged with nitrogen, and then magnesium chloride (2.6 g, 27 mmol), paraformaldehyde (1.2 g, 39 mmol), acetonitrile (20 mL) were added, and the temperature was 26 to 30 ° C. Stir.
Next, N, N, N ′, N′-tetramethylethylenediamine (3.1 g, 26 mmol) which is an amine compound is added, and 4,4 ′-(1-methylethylidene) bisphenol which is a commercially available hydroxyaryl compound ( 11) (1.5 g, 6.6 mmol) was added into the reaction solution. The reaction was carried out by stirring at a reaction temperature of 78 to 81 ° C. for 18 hours. A part of the reaction solution was sampled, and the conversion was 78% by HPLC analysis. After completion of the reaction, the reaction mixture was cooled to 15 to 20 ° C. and quenched with diluted hydrochloric acid adjusted to 2 mol / L, and then dichloromethane was added to separate the organic layer. The aqueous layer was combined with the organic layer re-extracted with dichloromethane, and the solvent was distilled off to obtain a crude product. Next, it refine | purified using column chromatography and obtained the binuclear 2-hydroxy aryl aldehyde compound (12) (1.4g, 73% of yield) of the target compound in the form of a pale yellow transparent oil. The obtained compound became a slightly yellowish white solid after several hours.
HPLC analysis conditions:
Column name Gemini 5u C18 110A (Phenomenex),
Eluent acetonitrile / water / acetic acid = 600/400/1 (v / v / v),
Flow rate: 1.0 mL / min, column temperature: 40 ° C., measurement wavelength: 230 nm.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 1.71 (s, 6H, CH ₃ ), 6.92 (d, J = 9.0 Hz, 2H, Ar), 7.35 (dd, J = 9 0.0 Hz, 2.4 Hz, 2H, Ar), 7.44 (d, J = 2.4 Hz, 2H, Ar), 9.86 (s, 2H, CHO), 10.94 (s, 2H, OH) .

撹拌機器と還流管を備えたフラスコを窒素置換した後、塩化マグネシウム（１．９ｇ，２０ｍｍｏｌ）を、パラホルムアルデヒド（０．９０ｇ，３０ｍｍｏｌ）を、テトラヒドロフラン（１８ｇ）を加え、２０〜２５℃にて撹拌した。
次に市販のアミン化合物であるＮ，Ｎ，Ｎ’，Ｎ’’，Ｎ’’−ペンタメチルジエチレントリアミン（２．３ｇ，２０ｍｍｏｌ）を加え、テトラヒドロフラン（２ｇ）に溶解させたヒドロキシアリール化合物（８）（２．０ｇ，１０ｍｍｏｌ）の溶液を、反応溶液中に加えた。反応温度を６４〜６６℃にて、３０時間撹拌して反応を行った。反応溶液の一部をサンプリングして、ＨＰＬＣ分析により転化率は、８５％であった。
ＨＰＬＣ分析条件：
カラム名 Ｌ−ｃｏｌｕｍｎＯＤＳ （化学物質評価研究機構），
溶離液 アセトニトリル／水／酢酸＝６００／４００／１（ｖ／ｖ／ｖ），
流量 １．０ｍＬ／ｍｉｎ，カラム温度 ４０℃，測定波長 ２３０ｎｍ．Example 5
A synthesis method of 2-hydroxy-2′-methoxy-1,1′-biphenyl-3-carbaldehyde (10) and (Reaction Scheme 8) are shown below.

A flask equipped with a stirrer and a reflux tube was purged with nitrogen, and then magnesium chloride (1.9 g, 20 mmol), paraformaldehyde (0.90 g, 30 mmol), and tetrahydrofuran (18 g) were added at 20 to 25 ° C. Stir.
Next, a commercially available amine compound N, N, N ′, N ″, N ″ -pentamethyldiethylenetriamine (2.3 g, 20 mmol) was added, and the hydroxyaryl compound (8) dissolved in tetrahydrofuran (2 g) A solution of (2.0 g, 10 mmol) was added into the reaction solution. The reaction was carried out at a reaction temperature of 64 to 66 ° C. with stirring for 30 hours. A part of the reaction solution was sampled, and the conversion was 85% by HPLC analysis.
HPLC analysis conditions:
Column name L-columnODS (Chemicals Evaluation and Research Institute),
Eluent acetonitrile / water / acetic acid = 600/400/1 (v / v / v),
Flow rate: 1.0 mL / min, column temperature: 40 ° C., measurement wavelength: 230 nm.

Example 6
The synthesis of 2-hydroxy-2 ′-(9-anthrylmethoxy) -1,1′-biphenyl-3-carbaldehyde (23) is described in the following (Reaction Scheme 9). “TMEDA” means N, N, N ′, N′-tetramethylethylenediamine.

(Synthesis of hydroxyaryl compounds)
Synthesis of 2 ′-(9-anthrylmethoxy) -1,1′-biphenyl-2-ol (22):
2,2-biphenol (4.10 g, 22 mmol), potassium carbonate (3.04 g, 22 mmol), potassium iodide (3.66 g, 22 mmol) and 26 mL of acetone were put into a reaction vessel and stirred with an oil bath. Was heated to 60 ° C. To this suspension, 9-chloromethylanthracene (21) (5.01 g, 22 mmol) was added and stirred at 60 ° C. for 20 hours. After confirming the reaction conversion rate by HPLC, a saturated aqueous ammonium chloride solution was added to stop the reaction. After liquid separation, the aqueous layer was extracted with ethyl acetate, combined and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography to obtain the hydroxyaryl compound (22) (3.01 g) as white crystals in a yield of 36.3%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.92 (s, 2 H, —OCH ₂ —), 6.46 (s, 1 H, —OH), 6.80 (dd, J = 8.0, 1.2 Hz, 1H), 6.94 (dt, J = 7.3, 1.2 Hz, 1H), 7.14-7.28 (m, 3H), 7.34-7.49 (m, 7H) ), 7.93 to 8.03 (m, 2H), 8.03 to 8.13 (m, 2H), 8.45 (s, 1H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2 ′-(9-anthrylmethoxy) -1,1′-biphenyl-3-carbaldehyde (23):
Paraformaldehyde (0.72 g, 31 mmol), anhydrous magnesium chloride (1.5 g, 31 mmol), N, N, N ′, N′-tetramethylethylenediamine (2.4 mL, 16 mmol) and acetonitrile (27 mL) were added to the reaction vessel. The temperature was kept at 85 ° C. The starting material (22) (3.0 g, 8 mmol) was added to this mixed solution and washed with acetonitrile (3.0 g). After stirring at 85 ° C. for 17 hours, 2 mol / L hydrochloric acid was added to stop the reaction. After neutralization, the aqueous layer from which acetonitrile was distilled off was extracted with ethyl acetate, the organic layer was washed with water (100 mL) three times, and then ethyl acetate was distilled off to obtain pale brown crystals. The crude product crystals were suspended and washed with isopropyl alcohol to obtain hydroxyaryl aldehyde (23) (1.86 g) as a pale yellow powder in a yield of 57.5% and HPLC relative area percentage of 89.2%. Obtained.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.90 (s, 2H, —O—CH ₂ —), 6.65 (t, J = 7.7 Hz, 1H), 7.08 to 7.20 (M, 2H), 7.25 to 7.32 (m, 2H), 7.35 to 7.50 (m, 6H), 7.87 to 7.97 (m, 2H), 8.12 to 8 .23 (m, 2H), 8.35 (s, 1H), 9.64 (s, 1H, -CHO), 11.15 (s, 1H, -OH).
HPLC analysis conditions:
Column name Inertsil ODS-3 4.6 × 150 mm × 3 μm,
Eluent acetonitrile / 20 mM aqueous sodium acetate solution = 96/4 (v / v),
Flow rate 1.0 mL / min, column temperature 40 ° C., retention time 2.5 minutes,
Analysis wavelength 280 nm.

Example 7
The synthesis of 2-hydroxy-2 ′-(4-methylbenzyloxy) -1,1′-biphenyl-3-carbaldehyde (33) is described in the following (Scheme 10).

(Synthesis of hydroxyaryl compounds)
Synthesis of 2 ′-(4-methylbenzyloxy) -1,1′-biphenyl-2-ol (32):
2,2-biphenol (3.72 g, 20 mmol), potassium carbonate (1.38 g, 10 mmol), potassium iodide (3.72 g, 20 mmol) and 23.5 mL of acetone were charged into the reaction vessel, and while stirring, The oil bath was heated to 60 ° C. To this suspension, p-methylbenzyl chloride (31) (2.81 g, 20 mmol) was added dropwise and stirred at 60 ° C. for 17 hours. After confirming the reaction conversion rate by HPLC, a saturated aqueous ammonium chloride solution was added to stop the reaction. After liquid separation, the aqueous layer was extracted with ethyl acetate, combined and concentrated to obtain a crude product. Purification by silica gel column chromatography (hexane / ethyl acetate = 9/1, Rf value = 0.25) gave the hydroxyaryl compound (32) (4.30 g) as white crystals in a yield of 74.0%. .
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 2.32 (s, 3 H, —CH ₃ ), 5.07 (s, 2 H, —OCH ₂ —), 6.41 (s, 1 H, —OH) 6.97-7.05 (m, 2H), 7.07-7.19 (m, 6H), 7.23-7.38 (m, 4H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2 ′-(4-methylbenzyloxy) -1,1′-biphenyl-3-carbaldehyde (33):
Paraformaldehyde (0.93 g, 31 mmol), anhydrous magnesium chloride (2.0 g, 31 mmol), N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (3.1 mL, 21 mmol) and tetrahydrofuran (30 mL). The reaction vessel was charged and the temperature was kept at 65 ° C. The starting material (32) (3.0 g, 10 mmol) was added to this mixed solution and washed with tetrahydrofuran (3.0 g). After stirring at 65 ° C. for 17 hours, 2 mol / L hydrochloric acid was added to stop the reaction. After separation, the aqueous layer was extracted with tetrahydrofuran, and the organic layers were combined and concentrated. The concentrate was dissolved in ethyl acetate (200 mL), washed three times with water (100 mL), and then ethyl acetate was distilled off to obtain pale brown crystals. The crystals were suspended and washed with isopropyl alcohol to obtain hydroxyarylaldehyde (33) (2.21 g) as a white powder in a yield of 67.4%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 2.31 (s, 3H, —CH ₃ ), 5.04 (s, 2H, —OCH ₂ —), 7.01 to 7.12 (m, 5H) ), 7.13 to 7.18 (m, 2H), 7.29 to 7.37 (m, 2H), 7.53 to 7.59 (m, 4H), 9.95 (s, 1H, − CHO), 11.34 (s, 1H, -OH).

Example 8
The synthesis of 2-hydroxy-2′-mesitylmethoxy-1,1′-biphenyl-3-carbaldehyde (43) is described in the following (Reaction Scheme 11).

(Synthesis of hydroxyaryl compounds)
Synthesis of 2′-mesitylmethoxy-1,1′-biphenyl-2-ol (42):
2,2-Biphenol (3.72 g, 20 mmol), potassium carbonate (2.76 g, 20 mmol), potassium iodide (3.32 g, 20 mmol) and 24 mL of acetone were put into a reaction vessel and stirred in an oil bath. Was heated to 60 ° C. To this suspension, 2,4,6-trimethylbenzyl chloride (41) (3.37 g, 20 mmol) was added and stirred at 60 ° C. for 17 hours. After confirming the reaction conversion rate by HPLC, a saturated aqueous ammonium chloride solution was added to stop the reaction. After liquid separation, the aqueous layer was extracted with ethyl acetate, combined and concentrated to obtain a crude product. The crude product was recrystallized from 2-propanol to obtain the hydroxyaryl compound (42) (5.93 g) as white crystals in a yield of 93.1%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 2.17 (s, 6 H, —CH ₃ ), 2.24 (s, 3 H, —CH ₃ ), 5.01 (s, 2 H, —OCH ₂ — ), 6.70 (s, 1H, —OH), 6.80 (s, 2H), 6.89 to 7.02 (m, 2H), 7.16 to 7.28 (m, 4H), 7 .32-7.43 (m, 2H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2′-mesitylmethoxy-1,1′-biphenyl-3-carbaldehyde (43):
Paraformaldehyde (0.90 g, 30 mmol), anhydrous magnesium chloride (1.9 g, 20 mmol), N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (3.0 mL, 20 mmol) and tetrahydrofuran (32 mL). The reaction vessel was charged and the temperature was kept at 65 ° C. The starting material (42) (3.2 g, 10 mmol) was added to this mixed solution and washed with tetrahydrofuran (3.2 g). After stirring at 70 ° C. for 17 hours, 2 mol / L hydrochloric acid was added to stop the reaction. After neutralization, the aqueous layer from which acetonitrile was distilled off was extracted with ethyl acetate, the organic layer was washed with water (100 mL) three times, and then ethyl acetate was distilled off to obtain a crude product. This crude product was suspended and washed with isopropyl alcohol to obtain hydroxyarylaldehyde (43) (1.57 g) as white crystals in a yield of 45.4% and a HPLC relative area percentage of 99.2%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 2.19 (s, 6 H, —CH ₃ ), 2.21 (s, 3 H, —CH ₃ ), 4.97 (s, 2 H, —O—CH ₂ −), 6.76 (s, 2H), 6.94 (t, J = 7.4 Hz, 1H), 6.75 (td, J = 7.3, 1.3 Hz, 1H), 7.18. ˜7.33 (m, 2H), 7.35 to 7.49 (m, 3H), 9.84 (s, 1H, —CHO), 11.21 (s, 1H, —OH).
HPLC analysis conditions:
Column name Inertsil ODS-3 4.6 × 150 mm × 3 μm,
Eluent acetonitrile / 20 mM aqueous sodium acetate solution = 96/4 (v / v),
Flow rate 1.0 mL / min, column temperature 40 ° C., retention time 2.5 minutes,
Analysis wavelength 254 nm.

Example 9
The synthesis of 2-hydroxy-2 ′-(2-naphthylmethoxy) -1,1′-biphenyl-3-carbaldehyde (53) is described in the following (Reaction Scheme 12).

(Synthesis of hydroxyaryl compounds)
Synthesis of 2 ′-(2-naphthylmethoxy) -1,1′-biphenyl-2-ol (52):
2,2-Biphenol (3.7 g, 20 mmol), potassium carbonate (2.8 g, 20 mmol) and 24 mL of acetone were added to the reaction vessel, and the oil bath was heated to 60 ° C. while stirring. To this suspension, 2- (bromomethyl) naphthalene (51) (4.42 g, 20 mmol) was added and stirred at 60 ° C. for 17 hours. After confirming the reaction conversion rate by HPLC, a saturated aqueous ammonium chloride solution was added to stop the reaction. After liquid separation, the aqueous layer was extracted with ethyl acetate, combined and concentrated to obtain a crude product. The crude product was recrystallized from 2-propanol to obtain the hydroxyaryl compound (52) (4.75 g) as white crystals in a yield of 72.8%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.27 (s, 2H, —OCH ₂ —), 6.31 (s, 1H, —OH), 6.97 to 7.08 (m, 2H) , 7.08-7.18 (m, 2H), 7.25-7.41 (m, 5H), 7.41-7.50 (m, 2H), 7.67-7.84 (m, 4H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2 ′-(2-naphthylmethoxy) -1,1′-biphenyl-3-carbaldehyde (53):
Paraformaldehyde (0.90 g, 30 mmol), anhydrous magnesium chloride (1.9 g, 20 mmol), N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (3.0 mL, 20 mmol) and tetrahydrofuran (33 mL). The reaction vessel was charged and the temperature was kept at 65 ° C. The starting material (52) (3.26 g, 10.0 mmol) was added to this mixed solution and washed with tetrahydrofuran (3.3 g). After stirring at 70 ° C. for 15 hours, 2 mol / L hydrochloric acid was added to stop the reaction. After neutralization, the aqueous layer from which acetonitrile was distilled off was extracted with ethyl acetate, the organic layer was washed with water (100 mL) three times, and then ethyl acetate was distilled off to obtain a crude product. This crude product was suspended and washed with isopropyl alcohol to obtain hydroxyarylaldehyde (53) (2.63 g) as white crystals in a yield of 74.1% and a HPLC relative area percentage of 99.0%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.17 (s, 2H, —O—CH ₂ —), 6.93 to 7.08 (m, 3H), 7.25 to 7.49 (m 6H), 7.55 (dd, J = 7.4, 1.8 Hz, 1H), 7.61-7.78 (m, 4H), 9.84 (s, 1H, -CHO), 11. 42 (s, 1H, -OH).
HPLC analysis conditions:
Column name Inertsil ODS-3 4.6 × 150 mm × 3 μm,
Eluent acetonitrile / 20 mM aqueous sodium acetate solution = 96/4 (v / v),
Flow rate 1.0 mL / min, column temperature 40 ° C., retention time 2.5 minutes,
Analysis wavelength 254 nm.

Example 10
The synthesis of 2-hydroxy-2 ′-(4-bromobenzyloxy) -1,1′-biphenyl-3-carbaldehyde (63) is described in the following (Reaction Scheme 13).

(Synthesis of hydroxyaryl compounds)
Synthesis of 2 ′-(4-bromobenzyloxy) -1,1′-biphenyl-2-ol (62):
2,2-Biphenol (3.72 g, 20 mmol), potassium carbonate (2.76 g, 20 mmol), potassium iodide (3.32 g, 20 mmol) and 24 mL of acetone were put into a reaction vessel and stirred in an oil bath. Was heated to 60 ° C. 4-Bromobenzyl bromide (61) (4.99 g, 20 mmol) was added to this suspension and stirred at 60 ° C. for 17 hours. After confirming the reaction conversion rate by HPLC, a saturated aqueous ammonium chloride solution was added to stop the reaction. After liquid separation, the aqueous layer was extracted with ethyl acetate, combined and concentrated to obtain a crude product. The crude product was recrystallized from 2-propanol to obtain the hydroxyaryl compound (62) (4.78 g) as white crystals in a yield of 67.3%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.05 (s, 2H, —OCH ₂ —), 6.11 (s, 1H, —OH), 6.97 to 7.19 (m, 6H) , 7.20-7.47 (m, 6H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2 ′-(4-bromobenzyloxy) -1,1′-biphenyl-3-carbaldehyde (63):
Paraformaldehyde (0.98 g, 33 mmol), anhydrous magnesium chloride (2.1 g, 22 mmol), N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (3.3 mL, 22 mmol) and tetrahydrofuran (36 mL). The reaction vessel was charged and the temperature was kept at 65 ° C. The starting material (62) (3.2 g, 10 mmol) was added to this mixed solution and washed with tetrahydrofuran (3.6 g). After stirring at 70 ° C. for 15 hours, 2 mol / L hydrochloric acid was added to stop the reaction. After neutralization, the aqueous layer from which acetonitrile was distilled off was extracted with ethyl acetate, the organic layer was washed with water (100 mL) three times, and then ethyl acetate was distilled off to obtain crystals of the crude product. . This crude product was suspended and washed with isopropyl alcohol to obtain hydroxyarylaldehyde (63) (2.64 g) as white crystals in a yield of 63.3% and a HPLC relative area percentage of 98.9%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.01 (s, 2H, —O—CH ₂ —), 6.92 to 7.18 (m, 5H), 7.27 to 7.45 (m , 3H), 7.51 to 7.61 (m, 3H), 9.95 (s, 1H, —CHO), 11.37 (s, 1H, —OH).
HPLC analysis conditions:
Column name Inertsil ODS-3 4.6 × 150 mm × 3 μm,
Eluent acetonitrile / 20 mM aqueous sodium acetate solution = 96/4 (v / v),
Flow rate 1.0 mL / min, column temperature 40 ° C., retention time 2.5 minutes,
Analysis wavelength 254 nm.

Example 11
The synthesis of 2-hydroxy-2 ′-(2-methoxybenzyloxy) -1,1′-biphenyl-3-carbaldehyde (73) is described in the following (Reaction Scheme 14).

(Synthesis of hydroxyaryl compounds)
Synthesis of 2 ′-(2-methoxybenzyloxy) -1,1′-biphenyl-2-ol (72):
2,2-Biphenol (3.7 g, 20 mmol), potassium carbonate (2.8 g, 20 mmol) and 24 mL of acetone were added to the reaction vessel, and the oil bath was heated to 60 ° C. while stirring. To this suspension, 2-methoxybenzyl chloride (71) (3.13 g, 20 mmol) was added and stirred at 60 ° C. for 17 hours. After confirming the reaction conversion rate by HPLC, a saturated aqueous ammonium chloride solution was added to stop the reaction. After liquid separation, the aqueous layer was extracted with ethyl acetate, combined and concentrated to obtain a crude product. The crude product was recrystallized from 2-propanol to obtain the hydroxyaryl compound (72) (5.58 g) as white crystals in a yield of 91.0%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 3.81 (s, 3 H, —OCH ₃ ), 5.15 (s, 2 H, —OCH ₂ —), 6.60 (s, 1 H, —OH) , 6.82 to 6.93 (m, 2H), 6.95 to 7.03 (m, 2H), 7.05 to 7.18 (m, 2H), 7.18 to 7.31 (m, 4H), 7.31-7.40 (m, 2H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2 ′-(2-methoxybenzyloxy) -1,1′-biphenyl-3-carbaldehyde (73):
Paraformaldehyde (0.90 g, 30 mmol), anhydrous magnesium chloride (1.9 g, 20 mmol), N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (3.0 mL, 20 mmol) and tetrahydrofuran (31 mL). The reaction vessel was charged and the temperature was kept at 65 ° C. The starting material (72) (3.26 g, 10.0 mmol) was added to this mixed solution and washed with tetrahydrofuran (3.1 g). After stirring at 70 ° C. for 15 hours, 2 mol / L hydrochloric acid was added to stop the reaction. After neutralization, the aqueous layer from which acetonitrile was distilled off was extracted with ethyl acetate, the organic layer was washed with water (100 mL) three times, and then ethyl acetate was distilled off to obtain crystals of the crude product. . The crude product was suspended and washed with isopropyl alcohol to obtain hydroxyarylaldehyde (73) (2.08 g) as white crystals in a yield of 62.1% and a HPLC relative area percentage of 99.2%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 3.81 (s, 2H, —O—CH ₃ ), 5.12 (s, 2H, —O—CH ₂ —), 6.74 to 6.89 (M, 2H), 6.97-7.13 (m, 3H), 7.13-7.26 (m, 2H), 7.26-7.39 (m, 2H), 7.49-7 .67 (m, 2H), 9.94 (s, 1H, -CHO), 11.29 (s, 1H, -OH).
HPLC analysis conditions:
Column name Inertsil ODS-3 4.6 × 150 mm × 3 μm,
Eluent acetonitrile / 20 mM aqueous sodium acetate solution = 96/4 (v / v),
Flow rate 1.0 mL / min, column temperature 40 ° C., retention time 2.5 minutes,
Analysis wavelength 254 nm.

Example 12
The synthesis of 2-hydroxy-2 ′-(2-fluorobenzyloxy) -1,1′-biphenyl-3-carbaldehyde (83) is described in the following (Reaction Scheme 15).

(Synthesis of hydroxyaryl compounds)
Synthesis of 2 ′-(2-fluorobenzyloxy) -1,1′-biphenyl-2-ol (82):
2,2-Biphenol (24.21 g, 130 mmol), potassium carbonate (8.98 g, 65 mmol), potassium iodide (4.32 g, 26 mmol) and 120 g of acetone were charged into a reaction vessel and stirred at 20 to 25 ° C. did. To this reaction solution was added 2-fluorobenzyl bromide (81) (24.57 g, 130 mmol), and the mixture was stirred at a reaction temperature of 60 ° C. for 23 hours. After cooling to 20 to 25 ° C., a saturated aqueous solution of ammonium chloride is added to the reaction solution to stop the reaction, and after separation, the aqueous layer is extracted with chloroform, the organic layers are combined and concentrated, and then silica gel column chromatography. By purifying by chromatography (hexane: ethyl acetate = 80: 20), the hydroxyaryl compound (82) (26.55 g) was obtained as light brown crystals in a yield of 69.4%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.17 (s, 2 H, —OCH ₂ —), 6.17 (s, 1 H, —OH), 6.97 to 7.20 (m, 7 H) , 7.22-7.43 (m, 5H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2 ′-(2-fluorobenzyloxy) -1,1′-biphenyl-3-carbaldehyde (83):
A flask equipped with a stirrer and a reflux tube was purged with nitrogen, and then paraformaldehyde (4.62 g, 154 mmol), anhydrous magnesium chloride (10.2 g, 107 mmol), starting material (82) (15.1 g, 51.2 mmol) And acetonitrile (100 mL) was added and it stirred at 20-25 degreeC. N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (11.84 g, 102 mmol) was added dropwise to the reaction solution. The reaction solution was stirred at a reaction temperature of 75 to 80 ° C. for 16 hours, cooled to 15 to 20 ° C., and 2 mol / L hydrochloric acid was added to stop the reaction. After neutralizing the reaction solution, the aqueous layer from which acetonitrile was distilled off was extracted with ethyl acetate, the organic layers were combined, and then the solvent was distilled off to obtain a crude product. The crude product was recrystallized in a chloroform-hexane-ethyl acetate system to obtain hydroxyarylaldehyde (83) (10.3 g) as pale white yellow crystals in a yield of 62.7%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 5.15 (s, 2H, —OCH ₂ —), 6.95 to 7.12 (m, 5H), 7.17 to 7.41 (m, 4H) ), 7.53-7.61 (m, 2H), 9.94 (s, 1H, -CHO), 11.32 (s, 1H, -OH).

Example 13
The synthesis of 2-hydroxy-2 ′-(2-phenylbenzyloxy) -1,1′-biphenyl-3-carbaldehyde (93) is described in the following (Reaction Scheme 16).

(Synthesis of hydroxyaryl compounds)
Synthesis of 2 ′-(2-phenylbenzyloxy) -1,1′-biphenyl-2-ol (92):
2,2-Biphenol (18.62 g, 100 mmol), potassium carbonate (6.91 g, 50.0 mmol), potassium iodide (3.32 g, 20.0 mmol) and acetone 90 g were charged into a reaction vessel and 20-25 Stir at ° C. To this reaction solution, 2-phenylbenzyl bromide (91) (24.71 g, 100 mmol) was charged, followed by stirring at a reaction temperature of 55 ° C. for 27 hours. After cooling to 20 to 25 ° C., the reaction was stopped by adding saturated aqueous ammonium chloride solution to the reaction solution, and after separation, the aqueous layer was extracted with chloroform, the organic layers were combined, concentrated, and then ethyl acetate-diisopropyl. By recrystallization in an ether-hexane system and purification, the hydroxyaryl compound (92) (34.38 g) was obtained as a yellow oil in a yield of 97.6%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 4.97 (s, 2H, —OCH ₂ —), 6.30 (s, 1H, —OH), 6.84 to 6.90 (m, 1H) 6.96-7.05 (m, 2H), 7.06-7.14 (m, 1H), 7.19-7.43 (m, 13H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2 ′-(2-phenylbenzyloxy) -1,1′-biphenyl-3-carbaldehyde (93):
A flask equipped with a stirrer and a reflux tube was purged with nitrogen, then paraformaldehyde (4.61 g, 154 mmol), anhydrous magnesium chloride (9.73 g, 102 mmol), starting material (92) (18 g, 51 mmol) and acetonitrile (144 g). ) Was added and stirred at 20-25 ° C. N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (11.86 g, 102 mmol) was added dropwise to the reaction solution. The reaction solution was stirred at a reaction temperature of 80 ° C. for 24 hours, cooled to 20 to 25 ° C., and 2 mol / L hydrochloric acid was added to stop the reaction. The reaction solution was neutralized and extracted with chloroform, and the organic solvent was distilled off to obtain a crude product. The crude product was recrystallized in a chloroform-hexane-ethyl acetate system to obtain hydroxyarylaldehyde (93) (10 g) as white crystals in a yield of 54%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 4.96 (s, 2H, —OCH ₂ —), 6.81 to 6.86 (m, 1H), 6.98 to 7.08 (m, 2H) ), 7.20-7.43 (m, 11H), 7.50-7.57 (m, 2H), 9.95 (s, 1H, -CHO), 11.33 (s, 1H, -OH) ).

Example 14
The synthesis of 2-hydroxy-2 ′-(2,4,6-tri-i-propylbenzyloxy) -1,1′-biphenyl-3-carbaldehyde (103) is described in the following (Reaction Scheme 17). To do.

(Synthesis of hydroxyaryl compounds)
Synthesis of 2 ′-(2,4,6-tri-i-propylbenzyloxy) -1,1′-biphenyl-2-ol (102):
2,2-biphenol (7.36 g, 39.5 mmol), potassium carbonate (2.84 g, 20.5 mmol), potassium iodide (1.32 g, 7.95 mmol) and acetone 35 g were charged into a reaction vessel, 20 Stir at ~ 25 ° C. 2,4,6-Tri-i-propylbenzyl chloride (101) (9.99 g, 39.5 mmol) was charged into the reaction solution, and then stirred at a reaction temperature of 55 ° C. for 39 hours. After cooling to 20 to 25 ° C., the reaction was stopped by adding a saturated aqueous solution of ammonium chloride to the reaction solution, and after separation, the aqueous layer was extracted with ethyl acetate, and the combined organic layer was dried over magnesium sulfate. Concentration gave the hydroxyaryl compound (102) (13.9 g) as pale orange white crystals in a yield of 87.2%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 1.10 (d, J = 6.9 Hz, 12H), 1.24 (d, J = 6.9 Hz, 6H), 2.86 (qq, J = 6.9 Hz, 1H), 3.04 (qq, J = 6.9 Hz, 2H), 5.06 (s, 2H), 6.45 (s, 1H), 6.87 to 7.01 (m, 4H), 7.14-7.29 (m, 4H), 7.34-7.46 (m, 2H).

(Synthesis of hydroxyaryl aldehyde compounds)
Synthesis of 2-hydroxy-2 ′-(2,4,6-tri-i-propylbenzyloxy) -1,1′-biphenyl-3-carbaldehyde (103):
A flask equipped with a stirrer and a reflux tube was purged with nitrogen, and then paraformaldehyde (3.13 g, 104 mmol), anhydrous magnesium chloride (6.62 g, 69.6 mmol), starting material (102) (14.0 g, 34.34). 8 mmol) and acetonitrile (100 mL) were added, and the mixture was stirred at 20 to 25 ° C. N, N, N ′, N′-tetramethylethylenediamine (TMEDA) (8.08 g, 69.6 mmol) was added dropwise to the reaction solution. The reaction solution was stirred at a reaction temperature of 80 ° C. for 37 hours, cooled to 20 to 25 ° C., and 2 mol / L hydrochloric acid was added to stop the reaction. The reaction solution was neutralized and extracted with dichloromethane, and the organic solvent was distilled off to obtain a crude product. The crude product was recrystallized in a chloroform-hexane-ethyl acetate system to obtain hydroxyarylaldehyde (103) (11.8 g) as white crystals in a yield of 78.5%.
¹ H-NMR (300 MHz, CDCl ₃ ) δ; 1.10 (d, J = 6.9 Hz, 12H), 1.22 (d, J = 6.9 Hz, 6H), 2.84 (qq, J = 6.9 Hz, 1H), 3.13 (qq, J = 6.9 Hz, 2H), 4.99 (s, 2H), 6.90-6.99 (m, 3H), 7.04-7. 12 (m, 1H), 7.20-7.31 (m, 2H), 7.39-7.49 (m, 3H), 9.85 (s, 1H), 11.20 (s, 1H) .

  The production method of the present invention can produce a 2-hydroxyaryl aldehyde compound with high chemical yield while suppressing by-products. Moreover, the 2-hydroxyaryl aldehyde compound which can be manufactured by this invention is useful as a ligand intermediate of a photosensitive resist composition, a curing agent, a developer or an asymmetric synthesis catalyst.

Claims (4)

Formula (1)

(In the formula (1), R ¹ , R ² , R ³ and R ⁴ are each independently a hydrogen atom, 1 to 3 phenyl groups (the phenyl group is unsubstituted or substituted with a substituent A and a hydroxy group) Substituted with one or more substituents selected from the same or different ones), and further substituted with one or more substituents selected from the same or different ones selected from a C _1-4 alkyl group and a halogen atom. An optionally substituted C _1-4 alkyl group, 1 to 3 phenyl groups (the phenyl group is unsubstituted or substituted by one or more substituents selected from the same or different substituents A and hydroxy groups). Substituted with one or more substituents selected from the same or different substituents selected from the substituent A and hydroxy group. ), A phenylsulfonyl group (the phenylsulfonyl group may be unsubstituted or substituted with one or more substituents selected from the substituent A and a hydroxy group) or a substituent A. ,
R ² and R ³ may be combined to form —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ —, wherein R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently hydrogen. An atom or substituent A,
Substituent A includes a halogen atom, a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _6-12 aryloxy group, a C _6-22 aryl group (the aryloxy group and the The aryl group may be unsubstituted or C _1-4 alkyl group, C _1-4 haloalkyl group, C _1-4 alkoxy group, C _1-4 alkylcarbonyloxy group, C _6-12 aryl group (the aryl group). The group is unsubstituted or substituted with one or more substituents which are the same or different and are selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group and a C _1-4 alkoxy group. , T-butyldimethylsilyl group, C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or C _1-4 alkyl group, C _1-4 alkoxy group, halogen atom and phenyl group) Substituted with one or more substituents selected from Are.) And is substituted with one or more substituents the same or different selected from halogen atom.), A substituent selected from nitro group or a cyano group. A hydroxyaryl compound represented by formula (a)

(R ⁹ in formula (a) is a C _1-3 alkyl group, or two R ⁹ on the same nitrogen atom together represent ═CH—R ¹⁰ ;
R ¹⁰ represents a C _6-12 aryl group (the aryl group is unsubstituted or one or more substituents selected from a C _1-4 alkyl group, a C _1-4 alkoxy group and a halogen atom). Substituted with a group)
n is 0 or an integer from 1 to 10. In the presence of an amine compound represented by the following formula (2):

(Wherein R ¹ , R ² , R ³ and R ⁴ are the same as described above). R ¹ is a hydrogen atom, a phenyl group (the phenyl group is unsubstituted or a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 alkylcarbonyloxy group) , A C _6-12 aryl group (the aryl group is unsubstituted or one or more same or different selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group, and a C _1-4 alkoxy group) A C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or a C _1-4 alkyl group, a C _1-4 alkoxy group, a halogen atom). And substituted with one or more substituents selected from the same or different selected from a phenyl group) and one or more substituents selected from halogen atoms) or a naphthyl group ( The naphthyl group is unsubstituted or C _1-4 An alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 alkylcarbonyloxy group, a C _6-12 aryl group (the aryl group is unsubstituted or C _1-4 alkyl Substituted with one or more substituents selected from the group, C _1-4 haloalkyl group and C _1-4 alkoxy group.), T-butyldimethylsilyl group, C _6-22 arylmethyloxy Group (the arylmethyloxy group is unsubstituted or substituted with one or more substituents which are the same or different and are selected from a C _1-4 alkyl group, a C _1-4 alkoxy group, a halogen atom and a phenyl group; And is substituted with one or more substituents selected from the same or different halogen atoms, and is optically active or optically inactive).
R ² is a hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, i-propyl group, t-butyl group, trifluoromethyl group or pentafluoroethyl group, and R ³ and R ⁴ are each independently hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, i-propyl group, t-butyl group, trifluoromethyl group, methoxy group, ethoxy group, i-propoxy The production method according to claim 1, which is a group or a t-butoxy group. R ¹ is a hydrogen atom, a phenyl group (the phenyl group is unsubstituted or a C _1-4 alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 alkylcarbonyloxy group) , A C _6-12 aryl group (the aryl group is unsubstituted or one or more same or different selected from a C _1-4 alkyl group, a C _1-4 haloalkyl group, and a C _1-4 alkoxy group) A C _6-22 arylmethyloxy group (the arylmethyloxy group is unsubstituted or a C _1-4 alkyl group, a C _1-4 alkoxy group, a halogen atom). And substituted with one or more substituents selected from the same or different selected from a phenyl group) and one or more substituents selected from halogen atoms) or a naphthyl group ( The naphthyl group is unsubstituted or C _1-4 An alkyl group, a C _1-4 haloalkyl group, a C _1-4 alkoxy group, a C _1-4 alkylcarbonyloxy group, a C _6-12 aryl group (the aryl group is unsubstituted or C _1-4 alkyl Substituted with one or more substituents selected from the group, C _1-4 haloalkyl group and C _1-4 alkoxy group.), T-butyldimethylsilyl group, C _6-22 arylmethyloxy Group (the arylmethyloxy group is unsubstituted or substituted with one or more substituents which are the same or different and are selected from a C _1-4 alkyl group, a C _1-4 alkoxy group, a halogen atom and a phenyl group; And is substituted with one or more substituents selected from the same or different halogen atoms, and is optically active or optically inactive).
R ² and R ³ together represent —CR ⁵ ═CR ⁶ —CR ⁷ ═CR ⁸ —, and R ⁵ and R ⁷ are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom. , Methyl group, ethyl group, i-propyl group, t-butyl group, trifluoromethyl group, methoxy group, ethoxy group, i-propoxy group or t-butoxy group, R ⁶ is a hydrogen atom, a fluorine atom, chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, i- propyl, t- butyl group, a trifluoromethyl group or pentafluoroethyl group, to claim 1 R ⁸ is a hydrogen atom or a fluorine atom The manufacturing method as described. R ⁹ represents a methyl group, an ethyl group, or two R ⁹ groups on the same nitrogen atom together represent ═CH—R ¹⁰ , and R ¹⁰ represents a phenyl group, a 2-fluorophenyl group, a 2-methylphenyl group, 2 The production method according to claim 1, which is -methoxyphenyl group or 2-i-propoxyphenyl group.