TW201002659A - Method of producing 2-hydroxyaryl aldehyde compound - Google Patents

Abstract

Disclosed is a process for producing a 2-hydroxyaryl aldehyde compound. Specifically disclosed is a process for producing a 2-hydroxyaryl aldehyde compound, which is characterized by comprising reacting a hydroxyaryl compound with paraformaldehyde in the presence of magnesium chloride and an amine compound represented by formula (a) [wherein R9 represents a C1-3 alkyl group, or two R9's on the same nitrogen atom together form =CH-R10; R10 represents a C6-12 aryl group (provided that the alkyl group is unsubstituted or substituted by a halogen atom); and n represents a number of 0 or an integer of 1 to 10].

Description

201002659 VI. Description of the Invention: [Technical Field] The present invention relates to a 2-hydroxy group which is suitable as a ligand for a photosensitive photoresist, a hardener, a color developer or a ligand intermediate of an asymmetric synthetic catalyst. A method for producing an aryl aldehyde compound. [Prior Art] There have been many reports on the methylation reaction of aromatic compounds (Non-Patent Document 1). A method of isomerizing a hydroxyaryl compound to produce an aryl aldehyde compound is as follows. (Previous method 1) Gattermann method: a method of reacting a hydroxyaryl compound with hydrogen cyanide using aluminum chloride or zinc chloride as a catalyst, or reacting cyanide with hydrogen chloride to produce an aryl aldehyde compound (Non-Patent Literature) 2. Non-patent literature 3). (Previous method 2) Gattermann-Koch method: A method of producing an aryl aldehyde compound by reacting carbon monoxide with hydrogen chloride in the presence of aluminum chloride and copper chloride (Non-Patent Document 4). (Previous Method 3) A method of using fluorinated formamidine and boron trifluoride (Non-patent Document 5). (Previous Method 4) A method of using dichloromethyl alkyl ether or an orthoformate: in the presence of titanium tetrachloride, aluminum chloride or tin chloride, the dichloromethyl alkyl ether or the orthoformate is subjected to The reaction is followed by hydrolysis to produce an aryl aldehyde compound (Non-Patent Document 6). -5- 201002659 (Previous method 5) Vilsmeier-Haack method: reacting a compound obtained by reacting phosphorus oxychloride, thionyl chloride or chlorinated herbicide with an N-substituted formamide compound to produce an aryl aldehyde compound Method (Non-Patent Document 7 and Non-Patent Document 8). (Previous method 6) Reimer-Tiemann reaction: A method of producing an aryl aldehyde compound by reacting chloroform, bromoform or trichloroacetic acid under a base (Non-Patent Document 9). (Previous method 7) Duff reaction: A method in which a hexamethyltetramine is reacted to produce an aryl aldehyde compound in the presence of glyceryl borate, acetic acid or trifluoroacetic acid (Non-Patent Document 1 and Non-Patent Document 1 1). (Previous Method 8) Catalyst method using a formaldehyde compound (paraformaldehyde, formaldehyde water, etc.); tin chloride compound (Non-Patent Document 12), titanium compound or pin compound (Patent Document 1, Patent Document 2), etc. For the catalyst. (Previous Method 9) A method of producing an aryl aldehyde compound by reacting a brominated aryloxymagnesium hydride with an I:1 complex of hexamethylphosphoniumamine (HMP A ) using a paraformaldehyde (Non-Patent Document 1) Non-Patent Document 14 and Non-Patent Document 15). (Previous method 10) A method of producing an aryl aldehyde compound by reacting a phenoxy magnesium salt compound prepared by catalyzing magnesium oxyhydroxide and a phenol compound using a paraformaldehyde (Patent Document 3, Non-Patent Document 16). (Previous Method 1 1) A method of producing an aryl aldehyde compound from a hydroxyaryl compound by using a paraformaldehyde to react a composition of magnesium chloride and triethylamine (Non-Patent Document 17 and Non-Patent Document 18). (Previous Method 12) A method of producing a aryl aldehyde compound by deprotecting a methoxymethyl group after lithiation and formazanization using a compound which protects the hydroxyaryl compound -6 - 201002659 with a methoxymethyl group ( Non-patent document 19) Patent document 2: JP-A-59-72536 Patent Document 2: JP-A-59-73 5 3 No. 7 Patent Document 3: Japanese Patent No. 3 3 73 228 Non-Patent Document 1: Chem. Rev. (1987), vol. 87, 671-686 ° Non-Patent Document 2: Organic Reactions (1957), 9 volumes, 37-72 ° Polysaccharides 3: J. Am. Chem. Soc. (1923 Year), Volume 45, 2373-2377 ° Non-Patent Document 4: Ber. (1 8 97), 30 volumes, 1 622-1 624 Non-Patent Document J. Am. Chem. S o c. (1 960) , 82 volumes, 2380-2382. Non-Patent Document 6: Chem. Ber. (1960), Vol. 93, 88-94. Non-Patent Document 7 ·· Ber_ (1927) '6〇B Volume' 119-122 ° Non-sounding literature g: Organic Synthesis Collective V olume3 (1955), 98-100 ° Non-Patent Document 9: Ber_ (1 876) 'Volume 9' 423·424 ° Non-Patent Document 1〇: Chem· Rev· (1 946) '38 Volume' 227-254 ° Non-Patent Document \ 1 : J. Ο r g. Chem. ( 1 994), Vol. 59, 201002659 1939-1942 ° Non-Patent Document 12: J. Chem. Soc. Perkin Trans I_ (1980), 1862-1865° Non-Patent Document 13: J_Chem. Soc. Perkin Trans I. ( 1978), 3 1 8-32 1. Non-Patent Document 14: 1_〇1. (: 1^111. (1993), Vol. 58, 1515-1522° Non-Patent Document 15: Bioorganic & Medicinal Chemistry (2007), Vol. 15, 3783-3800 ( Page 3793) ° Non-Patent Document 16: J. Chem. Soc. Perkin Trans I. (1994), 1 823 - 1 83 1 ° Non-Patent Document 17: Acta. Chemica. Scandinavica. (1999), Volume 53, 258-262 ° Non-Patent Document 18: Organic Synthesis, (205), 82, 64-67 ° Non-Patent Document 19: Synthetic Communications (1 9 7 5), 5(1), 65-78. SUMMARY OF THE INVENTION Problems to be Solved by the Invention In the methods of the above methods (Previous Method 1) to (Previous Method 7), the raw materials are toxic, and the products and by-products from the reaction are corrosive to the reaction device, so It has become an industrially advantageous method. The harvest rate is mostly moderate, so there will be low yield and by-products due to raw materials. -8-201002659. (Previous method 8), catalyst chlorine The tin compound is toxic. When the catalyst used is a titanium compound and a ruthenium compound, the reaction temperature is high. The degree of demand is above 150 °c, and neither the yield nor the by-products can be industrially advantageous. (Previous method 9), the hexamethylphosphoniumamine (HMPA) used is In addition to the carcinogenic substance, the Grignard reagent and the toxic benzene are used in order to prepare the bromo aryloxymagnesium, and thus it is not an industrially advantageous method. Further, the non-patent document 14 and the non-patent document 15 describe the improvement method. However, the use of Grignard reagent and hexamethylphosphoniumamine (HMPA) cannot be avoided. In the method of the prior method 10, the yield of the aldehyde is favored by the use of the toluene solvent, but by-products are formed in the reaction matrix. A diarylmethane compound. In addition, when the phenoxy magnesium salt compound is prepared, the solvent is removed by distillation, so that the method of industrial operation is not advantageous (previous method 1 1), the Casiraghi will be simple Improved method (Non-Patent Document 1 2, Non-Patent Document 13), which is a method for reacting a composition of magnesium chloride and triethylamine, and a method for producing an aryl yeast compound from a hydroxyaryl compound, although it can be avoided Amides with hexamethylphosphoramide carcinogenic substances (of HMPA), Comparative A are acylated using Casiraghi liter may provide a yield, but the problem byproducts. (Previous method 1 2) The method is 'a method for selectively formazing the ortho position of a hydroxyaryl compound, but in order to obtain a target system having a substituent, it is not possible to achieve a one-stage reaction, but to protect the substituent, The methylation reaction and the 3-stage reaction of the deprotection of the substituent cannot be industrially advantageous as the -9-201002659 method. Further, in the method, the hydroxyaryl compound in which the substituent is a halogen and the hydroxyaryl compound having a benzyl moiety have a problem that the lithiation reaction cannot be controlled to produce a by-product. Therefore, in order to simultaneously achieve inhibition of by-products and increase the yield, an industrially useful method for producing a 2-hydroxyaryl aldehyde compound is required. MEANS FOR SOLVING THE PROBLEMS The present inventors have focused on the industrially useful method for producing a 2-hydroxyaryl aldehyde compound, and found that a reaction of a composition of magnesium chloride and triethylamine is carried out using para-formaldehyde, which is produced from a hydroxyaryl compound. In the method of the 2-hydroxyaryl aldehyde compound (Non-Patent Document 17 and Non-Patent Document 18), the reaction system uses bismuth (i) base with respect to the triethylamine having a base function used in the reaction. Functionality and (ii) when a plurality of ligands for the coordination function of the magnesium reaction intermediate are stabilized, the amine compound is used, and the by-product can be inhibited from the prior art while producing the 2-hydroxyaryl aldehyde compound at a high yield. The present invention has been completed. That is, the present invention is [1] a following formula (2) [Chemical 3]

(In the above formula, a method for producing a 2-hydroxyl aldehyde compound represented by R1, R2, R3 and R4 is as follows), characterized in that the existence formula -10- 201002659 1 9 R-

R-N R-Nr

9 R (in the formula (a), R is a C^k group, or the same - two R9 groups on the nitrogen atom form =CH-R1C) 'R10 is a C^2 aryl group (the aryl group is unsubstituted, or An amine compound represented by a Ci4 alkyl group, a G-4 alkoxy group, and a halogen atom selected by the same or different one or more substituents, wherein 'η is 〇 or an integer of 1 to 1 〇, [Chemical 1] R4

R3 R1 (1 ) R2- —ΟΗ (In the formula (1), R1, R2, R3 and V are each independently a hydrogen atom of 1 to 3 phenyl groups (the phenyl group is unsubstituted or substituted by octaves and a Cl.4 compound, which is substituted by the same or different one or more substituents, and which is substituted by the C!_4 alkyl group and the halogen atom, which is substituted with the same or different one or more substituents. a phenyl 'phenylcarbenyl group substituted to three phenyl groups (which are unsubstituted or substituted with one or more substituents selected from the same or different substituents in the hydroxyl group) The base is non-generation, or is selected by the substituent A and the hydroxyl group to be the same or different & one: substituent substituted), phenylsulfonyl (the phenyl polymer is unsubstituted, | -11 - 201002659 R1 and R3 may be formed together by substituent A and the same or different substituents in the hydroxy group. R2 and R3 may form together -CR5 = CR6-CR7 = CR8 R6, R7 and R8 are each independently a hydrogen atom or a substituent A Substituent A is a halogen atom, a Cm alkyl group, a C 4 halooxy group, an aryloxy group, a C6-22 aryl group (the aryloxy group is substituted, or is C!-4 alkyl group, Cu haloalkyl group, Cl 4 Home base carbon methoxy Chu aryl (the aryl group is unsubstituted, the base 'Cl-4 sulfonyl group and the C!·4 oxy group are substituted with the same substituents above), t-butyl dimethyl decyl group, c group ( The arylmethoxy group is unsubstituted, or is selected by the C1_4 yard group, the halogen atom and the phenyl group in the same or different ones) and the halogen atom is selected as the same or different one, and the nitrate The substituent represented by the substituent in the cyano group or the cyano group is reacted with anhydrous magnesium chloride and paraformaldehyde to form a methoxy group ortho-selectively methylated; [2] The production method according to [1], wherein benzene a group (the phenyl group is unsubstituted or substituted by a C 4 alkyl group, a C1·4 alkoxy group, a Cl-4 amphoteric carbon azeooxy group, a c6.12 aryl group, or a Cl·4 alkyl group, C^ 4 haloalkyl and Ci4 alkane are substituted by one or more substituents which are the same or different), c6.22 The arylmethoxy group is unsubstituted or is selected by d-4 alkyl, Ci atom and phenyl group Or one or more of the different ones and the halogen atoms are selected to be the same or different one or more substituents - in this case, R5, the hospital base, the C _ 4 hospital and the aryl group are no radicals, C 1 · 4 homes or by C! -4 R1 of an alkane or a different -6·22-square-methyl methoxy group, a substituent of the above-mentioned hydroxy-arylated aryl compound substituted with a substituent, and a hydrogen atom, a Cl-4 haloalkyl group, An aryl or oxy group selected from the group consisting of an aryl methoxy group (- 4 I methoxy group, a halogen substituent substituted with a substituent) or a -12- 201002659 naphthyl group (the naphthyl group is unsubstituted or is a Cl_4 alkane) a group, a Cl_4 haloinyl group, a C1-4 alkoxy group, a C|·4-yard carbamethoxy group, a Cm aryl group (the aryl group is unsubstituted or is a G.4 alkyl group, c]_4 haloalkyl group And the same or different one or more substituents selected in the Cl_4 alkoxy group), t-butyldimethyl group, the Cm aryl methoxy group (the aryl methoxy group is unsubstituted, or Substituted by Ci4 alkyl, C!-4 alkoxy, halogen atom and one or more substituents selected from the same or different substituents in the phenyl group) and substituted by one or more substituents selected from the same or different halogen atoms Also optically or optically inactive), R is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a monumental atom, a methyl group, an ethyl group, an i-propyl group, a t-butyl group, a trifluoromethyl group or a pentafluoro group. Ethyl, R3 and R4 are each independently 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, a methoxy group, an ethoxy group, and i. (3) The production method according to [1], wherein Ri is a hydrogen atom or a phenyl group (the phenyl group is unsubstituted or is Ci 4 alkyl, Ci 4 haloalkane). Base, Ci-4, oxy, C!·4, carbaryl, c6_12 aryl (the aryl group is unsubstituted or is C?·4, K4, C4, and C4) One or more substituents of the same or different substituents are selected), C6.22 aryl methoxy (the aryl methoxy group is unsubstituted, or is a C 4 alkyl group, a C. 4 alkoxy group, a halogen atom and One or more substituents selected from the same or different substituents in the phenyl group) and one or more substituents selected from the same or different substituents in the halogen atom) or a naphthyl group (the naphthyl group is unsubstituted or is subjected to Cl 4 ) Alkyl, Cl_4_alkyl, alkoxy, C..4 carbene carbonyl, c6_12 aryl (the aryl is unsubstituted or is C?_4, Cl-4 haloalkyl and ^Alkoxy selected 13-201002659 identical or different More than one substituent substituted), t-butyldimethylsilyl, C6'22 aryl methoxy (the aryl methoxy group is unsubstituted, or is Ci4k-based, Cl.4 alkoxy And one or more substituents selected from the same or different halogen atoms in the halogen atom and the phenyl group) and one or more substituents selected from the same or different ones in the halogen atom are further optically active or optically inactive, R And R3 can form _cr5 = cr6_cr7 = cr8·, and R and R7 are each independently 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, Trifluoromethyl, methoxy, ethoxy, i.propoxy or t. butoxy, R6 is a hydrogen atom, a fluorine atom, a chlorine atom 'bromine atom, an iodine atom 'methyl, ethyl, i- a propyl group, a t-butyl group, a trifluoromethyl group or a pentafluoroethyl group, and R8 is a hydrogen atom or a fluorine atom; [4] The production method as described in [丨], wherein R9 is a methyl group, an ethyl group or the same nitrogen atom. The above two R9s together form =CH_Ri〇, R is a yl group, a 2-oxophenyl group, a 2-methylphenyl group, a 2-methoxyphenyl group or a 2-i-propoxyphenyl group. EFFECTS OF THE INVENTION The present invention can suppress by-products and produce a 2-hydroxyaryl aldehyde compound at a high chemical recovery rate. Further, the hydroxyaryl aldehyde compound produced by the present invention is suitably used as a material for a photosensitive photoresist composition, a curing agent, a color developing agent, or a ligand intermediate of an asymmetric coupling catalyst. BEST MODE FOR CARRYING OUT THE INVENTION-14- 201002659 In this manual, “η” means “正”, “丨” means “和”, “t”, “曰”, “e”, “'” means “neighborhood” "P" means right. "M e" means methyl,"

, "Bu" means butyl, "TMEDA" is N, N, N

Et2〇 2-bondyl aryl aldehyde compound means "extension" means "ethyl", N'-tetramethylexene I diethylethyldiamine, and "THF" means tetrahydrofuran ether. The invention will be described in detail below. The method of producing the present invention is characterized by the existence of the formula (i) [Chemical 4] R2

OH (in the formula (1) is substituted by 1 to 3 phenyl groups (the phenyl group is unsubstituted, or is taken from 1, 碁A and the same or different substituents selected from the residues are taken as w π) And may be selected by the 4·4 alkyl group and the halogen atom with the same or opposite — m — < 1 or more substituents substituted by 1S 3 phenyl groups (the phenyl group is unsubstituted, ... and R4 Each of which is independently a hydrogen atom or a substituted phenyl or phenyl carbon (tetra) substituted with the same or different i or more substituents selected from the substituent A and the hydroxyl group (the phenylcarbon group is unsubstituted or substituted) a substituent of the same or different substituents selected from the group A and the hydroxyl group), a phenylsulfonyl group (the phenylsulfonyl group is unsubstituted, or may be selected by the substituents 8 and the same or the same in the hydroxyl group) Substituted with one or more substituents) or substituents A, R and R3 may form together -CR5 = CR6-CR7 = CR8-, in which case, -15-201002659 R, R7 and R8 are each independently a hydrogen atom or a substituent A, —Substituent A is a halogen atom, a Cl.4 compound, a Ci4 halogen, and a Ci4 methoxy C6_丨2 cyclyl 'C6-22 aryl group (the aryloxy group and the aryl group are Substituted, or by C" alkyl, Cl_4 haloalkyl, Ci 4 alkoxy, C" alkyl carbaoxy, C6 heart aryl (the aryl group is unsubstituted, or is ci4, q_4 alkane And the C1_4 alkoxy group selected the same or different one or more substituents substituted), t-butyldimethylmethylalkyl, C6 22 aryl methoxy (the aryl methoxy group is unsubstituted, Or substituted by a c14 alkyl group, a c14 alkoxy group, a halogen atom and a phenyl group selected by the same or different i or more substituents) and the same or different i or more substituents selected from the halogen atom), a hydroxyaryl compound represented by a substituent selected from a nitro group or a cyano group, anhydrous magnesium chloride, paraformaldehyde, and (a) W匕5] R9 r9-n R9 R9 N-Re (in the formula (a) R9 is Ci-3's base' or 2 R9 on the same nitrogen atom to form =CH-R1(), R1() is c6.12 aryl (the aryl group is unsubstituted or is Cl.4 alkyl , in the presence or absence of triethyl, in the presence or absence of an amine compound represented by a C i alkoxy group and a halogen atom selected by the same or different one or more substituents, and η is 0 or an integer of 1 to 10) Under the amine Anhydrous magnesium chloride and paraformaldehyde the reaction, the ortho-hydroxy aryl carboxylic selective acylation of the compound, can be obtained by the following formula (2-16-201002659 [Formula 6]

(In the above formula, the 2-hydroxyaryl aldehyde compound represented by 'R1, 15·2, r3 and R4 as defined above). The respective substituents and partial structures in the above formulas (1) and (2) will be explained below. In the above formulas (1) and (2), R^R2, ! ^3 and R4 are each independently a hydrogen atom, substituted by 1 to 3 phenyl groups (the phenyl group is unsubstituted, or substituted by the substituent A and the same or different one or more substituents selected from the hydroxyl group), and a C i ·4 alkyl group which may be substituted by a C 1 · 4 fluorenyl group and one or more substituents selected from the same or different halogen atoms, and is 1 to 3 phenyl groups (the phenyl group is unsubstituted 'or a substituted phenyl or phenylcarbenyl group substituted with one or more substituents selected from the same or different substituents in the hydroxyl group (the phenylcarbenyl group is unsubstituted or substituted by a substituent A and a hydroxyl group) One or more substituents of the same or different substituents are selected), phenylsulfonyl (the phenylsulfonyl group is unsubstituted) or one or more substituents which may be selected by the substituent A and the same or different from the hydroxyl group The substituents or the substituents A, R2 and R3 may form together _CR5 = cr6_cr7 = CrS_, in which case, R, R7 and r8 are each independently a hydrogen atom or a substituent A, and the substituent A is a halogen atom, C]_4 Alkyl, Cl. 4 haloalkyl ' Ci_4 alkoxy, Cm aryloxy, aryl (the aryloxy group and the aryl group are substituted by -17-201002659, or by Cw alkane , q-based carbonoxy, C0_12 aryl (•4-haloalkyl, CU4 alkoxy, Ci_4 alkane, the aryl group is unsubstituted, or is C!.4 alkyl, C,-4 haloalkyl and ^_4 alkoxy group selected from the same or different substituents substituted by more than one substituent), t-butyldimethyl sand compound, 匕22 aryl methoxy (the aryl methoxy group is unsubstituted) Or substituted by a c14 alkyl group, a C14 alkoxy group, a halogen atom and one or more substituents selected from the same or different substituents in the group) and one or more substituents selected from the same or different halogen atoms) a substituent selected from a nitro group or a cyano group. The RI in the above formula (1) and formula (2) will be specifically described below. The halogen atom such as a 'fluorine atom, a chlorine atom, a bromine atom and an iodine atom. 3^4 alkyl such as methyl, ethyl, η-propyl, i-propyl, n-butyl, i-butyl, s-butyl and t-butyl, etc. The C!_4 courtyard oxygen Such as 'methoxy, ethoxy, n-propoxy, i-propoxy, η-butoxy, i-butoxy, 8-butoxy and t-butoxy, etc.. Alkoxy such as phenoxy, 1-naphthyloxy, 2-naphthyloxy, 2-biphenyloxy, 3-biphenyl And 4-biphenoxy, etc. The Cl_4 haloalkyl group, such as fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, chlorofluoromethyl, dichloromethyl, bromofluoro Methyl, trifluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trichloromethyl, bromodifluoromethyl, bromochlorofluoromethyl, dibromofluoromethyl, 2-fluoroethyl, 2 -Chloroethyl, 2-bromoethyl, 2,2-difluoroethyl, 2-chloro-2-fluoroethyl, 2,2-dichloroethyl, 2-bromo-2-fluoroethyl, 2 , 2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, 2-bromo -2,2-difluoroethyl, 2-bromo-2-chloro-2-fluoroethyl, 2-bromo-2,2-dichloroethyl, 1,1,2,2-tetrafluoroethyl, Pentafluoroethyl, 1-chloro-l,2,2,2-tetrafluoroethyl, 2-chloro-l,l,2,2-tetrafluoroethyl, l,2-dichloro--18- 201002659 "2,2-Trifluoroethyl, ^"-tetrafluoroethyl fluoropropyl" chloropropyl, 2-bromopropyl, 2-chloro-2-fluoropropyl, 2,3-dichloropropane Fluoropropyl, 3-bromo-2-chloropropyl, 2^'3' '~bromopropyl, 3,3,3_ξ, 3-bromo-3,3-difluoropropyl, 2,2 3 3 & base,, 3' tetrafluoropropyl, 2-chloro_3,3 3 = Base, 2,2,3,3,3-pentafluoropropyl', monofluoro 3,3-hexafluoropropyl, hepta, 2,3-dichloro-1,1,2,3,3-five Fluorocarbon group, 2. fluoro small methyl ethyl chloride small methyl ethyl group, 2. bromine small methyl ethyl group, 2, 2, 2 - trifluoromethane (-yi 2) ethyl group, 1, 2, 2 ,2-tetrafluoro]-chloromethyl(trifluoromethyl)ethyl 2.2.3.3.4.4- hexafluorobutyl, hydrazine, * 2,2,3,4,4,4_ hexafluorobutene 2.2.3.3.4.4 .4-Heptafluorobutyl, ^,, 2,3,3,4,4-octafluorobutyl, butyl, 4-chloro-1,1,2,2,3,3,4,4-eight Fluorine butyl fluoride, 2-fluoro 2 -methylpropane 2 -chloro-1,1-dimethylethyl and 2-dimethyl phthalate. The above formula (1) and the formula (1) towel R1_c-base will be explained below. The C6-22 aryl group is, for example, phenyl 622-square-dwelling (children phenyl is unsubstituted, or c-alkyl, C-tetrahaloalkyl-Cm-alkane--4 machine-based, Cm alkyl-carbon fluorene Oxygen, aryl (the aryl group is unsubstituted, or her 6-12 4 is selected by the Cb4 alkyl group, the Cl. 4 decyloxy group, the same or the opposite phase and the H 丨 J phase) Substituent, C6-22 aryl methoxy (the methoxy group is unsubstituted, or is c-based, Ci_4, oxy, halogen atom along ~ 4 囟 atom and the base The same one or more substituents are selected to be substituted) and -e, ,, /, the same or more than one substituent are selected in the sub), and the biphenyl- π group (the n- group is unsubstituted, Ci-4 alkyl, Ci_4 dentate alkyl, oxy, C6, alkoxy, Cm alkylcarbenyloxy 6.12 square group (the aryl group is unsubstituted, or is c-hospital, dentate alkyl and Among the Cl.4 alkoxy groups, the same or different ones are selected as the above-mentioned substitutions -19-201002659, the base-substituted 't_T-based dimethyl fluorenyl group, C6_22 aryl methoxy group (the aryl methoxy group is unsubstituted γ) -Η- η 吟## ^ ^ ^ or by C--4 yard base, C]_4 courtyard oxygen And one or more substituents selected from the same or different ones of the halogen atom and the phenyl group) and one or more substituents selected from the same or different halogen atoms, which are optically active or optically inactive. The C 6-22 aryl group of R1 in the above formula (1) and formula (2) will be specifically described. The C6-22 aryl group is, for example, phenyl, 2-methylphenyl, 2-trifluoromethylphenyl , 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 2-pentafluoroethylphenyl, 2-n-propylphenyl, 2-i-propylphenyl, 2-7 Fluorine-n-propylphenyl, 2-heptafluoro-i-propylphenyl, 2-n-butylphenyl, 2-i-butylphenyl, 2-s-butylphenyl, 2_t- Butylphenyl, 2-9 nonafluoro-n-butylphenyl, 2-9-fluoro-t-butylphenyl, 2,6-dimethylphenyl, 2,6-ditrifluoromethylphenyl, 3,5-Dimethylphenyl, 3,5-ditrifluoromethylphenyl, 2,6-diethylphenyl, 2,6·dipentafluoroethylphenyl, 3,5·diethyl Phenyl, 3,5-dipentafluoroethylphenyl, 2-methoxyphenyl, 2-(indolylmethoxy)phenyl, 2-(2-decylmethoxy)phenyl , 2-(9-fluorenylmethoxy)phenyl, 2-(1-phenanthrylmethoxy)phenyl 2-(2-phenanthrylmethoxy)phenyl, 2-(3-phenanthrylmethoxy)phenyl, 2-(4-phenanthryloxy)phenyl, 2-(9-phenanthrylmethoxy) Phenyl, 2-(1-indolylmethoxy)phenyl, 2-tolylmethoxyphenyl, 2-(1-naphthylmethoxy)phenyl, 2-(2-naphthylmethyl) Oxy)phenyl, 2-(2-diphenylmethoxy)phenyl, 2-(3-diphenylmethoxy)phenyl, 2-(4-biphenylmethoxy)phenyl , 3-methoxyphenyl, 4-methoxyphenyl, 2·ethoxyphenyl ' 3-ethoxyphenyl, 4-ethoxyphenyl, 2-i-propoxyphenyl , 3-i-propoxyphenyl, 4-i-propoxyphenyl, 2-n-butoxy-20- 201002659, 2-i-butoxy-based, 2-s-butoxy Phenyl, 2-t-butoxy, benzo, 3-n-butoxyphenyl, 3-i-butoxyphenyl, 3-s-butoxyphenyl, 3-t-butoxy Phenylphenyl, 4-n-butoxyphenyl, 4-i-butoxyphenyl, 4-s-toxyphenyl, 4-t-butoxyphenyl, 2,6-dimethoxy Phenyl, 3,5-dimethoxyphenyl, 2,6-diethoxyphenyl, 3,5-diethoxyphenyl, 2,6---i-propoxyphenyl , 3,5 - _^-i-propoxyphenyl, 2-methyl carbon Benzo, 2-ethylcarbocyloxy, 2-n-propylcarbomethoxyphenyl, 2-i-propylcarbonoxyphenyl, 2-n-butylcarbenyloxyphenyl , 2-i-butylcarbenyloxyphenyl, 2-s-butylcarbenyloxyphenyl, 2-t-butylcarbenyloxyphenyl, 2-benzyloxyphenyl, 2- (2-methylbenzyloxy)phenyl, 2-(3-methylkethoxy)phenyl, 2-(4-methylbenzyloxy)phenyl, 2-(2-i-propylbenzyl Oxy)phenyl, 2-(3-i-propylbenzyloxy)phenyl, 2-(4-i-propylbenzyloxy)phenyl, 2-(2,4,6-tri-i -propylbenzyloxy)phenyl, 2-(2-fluorobenzyloxy)phenyl, 2-(3-fluorobenzyloxy)phenyl, 2-(4-fluorobenzyloxy)phenyl, 2 - (2-Bromobenzyloxy)phenyl, 2-(3-bromobenzyloxy)phenyl, 2-(4-bromobenzyloxy)phenyl, 2-(2-methoxybenzyloxy) Phenyl, 2-(3-methoxybenzyloxy)phenyl, 2-(4-methoxybenzyloxy)phenyl, 5-bromo-phenyl, 5-bromo-2-methylphenyl , 5-bromo-2-trifluoromethylphenyl, 5-bromo-3-methylphenyl, 5-bromo-4-methylphenyl, 5-bromo-2-ethylphenyl, 5-bromo -2 - pentafluoroethylphenyl, 5-bromo-2-n-propylphenyl, 5-bromo-2-i-prop Basic group, 5-di-pyridin-2-hexa-propyl-propylphenyl, 5-di-ki-7-qi-i-propylphenyl, 5-bromo-2-n-butylphenyl, 5- Bromo-2-i-butylphenyl, 5-bromo-2-s-butylphenyl, 5-bromo-2-t-butylphenyl, 5-bromo-2-nonafluoro-η-butyl Phenyl, 5-dioxa-2-nine gas|-t-butyl base, 5-di--2,6- _methyl-based, 5_-21 - 201002659 bromo-2,6-ditrifluoromethylphenyl , 5-bromo-2,6-diethylphenyl, 5-bromo-2,6-dipentafluoroethylphenyl, 5-bromo-2-methoxyphenyl, 5-bromo-3-methyl Oxyphenyl, 5-bromo-4-methoxyphenyl, 5-bromo-2-ethoxyphenyl, 5-bromo-3-ethoxyphenyl, 5-oxa-4-ethoxy 5-, 5-hydroxy- 2-i-propoxy-based, 5-bromo-3-i-propoxyphenyl, 5-bromo-4-i-propoxyphenyl, 5-bromo-2-n -butoxyphenyl, 5-ismo-2-i-butoxybenyl, 5-dioxa-2-s-butoxybenyl, 5-bromo-2-t-butoxyphenyl, 5-bromo- 3-n-butoxyphenyl, 5-bromo-3-i-butoxyphenyl, 5-oxa-3-s-butoxybenyl, 5-oxa-3-tert-butoxy-based, 5_Bromo-4-n-butoxyphenyl, 5-bromo-4-i-butoxyphenyl, 5-bromo-4-s-butoxyphenyl, 5-indi-4-t-butyl Oxybenyl, 5-di-2,6 - __•Methane base, 5-bromo-2,6-diethoxyphenyl, 5-bromo-2,6-di-i-propoxyphenyl, 5-bromo-2-methyl carbon Nonyloxyphenyl, 5-bromo-2-ethylcarbenyloxyphenyl, 5-bromo-2-n-propylcarbonoxyphenyl, 5-bromo-2-i-propylcarbazide Oxyphenyl, 5-bromo-2-n-butylcarbenyloxyphenyl, 5-bromo-2-i-butylcarbenyloxyphenyl, 5-oxa-2-s-butyl carbon Oxygen-based, 5-di-2-t-butylcarbomethoxy, 5-bromo-2-benzyloxyphenyl, 5-iodo-phenyl, 5-iodo-2-methylphenyl 5-iodo-2-trifluoromethylphenyl, 5-iodo-3-methylphenyl, 5-iodo-4-methylphenyl, 5-iodo-2-ethylphenyl, 5-iodo -2-pentafluoroethylphenyl, 5-iodo-2-n-propylphenyl, 5-iodo-2-i-propylphenyl, 5-iodo-2-heptafluoro-η-propylbenzene , 5-iodo-2-heptafluoro-i-propylphenyl, 5-iodo-2-n-butylphenyl, 5-iodo-2-i-butylphenyl, 5-iodo-2- S-butylphenyl, 5- sure:-2-t-butylphenyl, 5-yao-2-nine-n-butylphenyl, 5-amino-2-9 per-1; Phenyl, 5- sure-2,6- _methylamino, 5-indole-2,6-ditrifluoromethylphenyl, 5-iodo-2,6-diethylphenyl' 5-iodo -2,6-dipentafluoro-22- 201 002659 ethyl phenyl, 5-iodo-2-methoxyphenyl, 5-iodo-3-methoxyphenyl, 5-iodo-4-methoxyphenyl, 5-iodo-2-ethoxy Phenylphenyl, 5-iodo-3-ethoxyphenyl, 5- sure-4-ethoxybenyl, 5-ya-2-i-propoxy-based, 5-react: -3 - i _ Oxyphenyl, 5-iodo-4_i-propoxyphenyl, 5-iodo-2-n-butoxyphenyl, 5-iodo-2-i-butoxyphenyl, 5-letogram-2 - s-butoxyphenyl, 5-iodo-2-t-butoxyphenyl, 5-iodo-3-n-butoxyphenyl, 5-iodo-3-i-butoxyphenyl , 5-t-3-s-butoxy-based, 5-pic-3-t-butoxyphenyl, 5-au-4-n-butoxyphenyl, 5-iodo-4-i-butyl Oxyphenyl, 5-iodo-4-s-butoxyphenyl, 5-iodo-4-t-butoxyphenyl, 5-iodo-2,6-dimethoxyphenyl, 5- Iodine-2,6-diethoxyphenyl, 5-iodo-2,6-di-i-propoxyphenyl, 5-iodo-2-methylcarbenyloxyphenyl, 5-iodo- 2-ethylcarbonoxyphenyl, 5-iodo-2-n-propylcarbonoxyphenyl, 5-iodo-2-i-propylcarbonoxyphenyl, 5-iodo-2 -n-butyl carbon-branched oxy-based, 5-A-2-i-butyl-carto-oxyphenyl, 5--:-2- s-butyl-carbonoxy-based base, 5-letogram- 2-t-butylcarboyloxyphenyl, 5-indol-2-benzyloxyphenyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, 1-naphthyl, 2- Naphthyl, 2-methyl-1-naphthyl, 2-trifluoromethyl-1-naphthyl, 2-ethyl-1-naphthyl, 2-pentafluoroethyl-1-naphthyl, 2-n -propyl-1-naphthyl, 2-i-propyl-1-nyl, 2-penta-η-propyl-1-caiyl, 2 -hepta-i-propyl-1-naphthyl , 2-n-butyl-1-naphthyl, 2-i-butyl-1-naphthyl, 2-s-butyl-1-nyl, 2-t-butyl-1-nyl, 2 -Nine gas-η-butyl-1-nyl, 2·nonafluoro-t-butyl-1-naphthyl, 2-methoxy-1-naphthyl, 2-ethoxy-1-naphthyl 2-i-propenyl-1-nyl, 2-n-butoxy-1-naphthyl, 2-i-butylene-1-naphthyl, 2-s-butoxy-1- Naphthyl, 2-t-butoxy-1-naphthyl, 2-methylcarb-23- 201002659 醯oxy-1-naphthyl, 2-ethylcarbenyloxy-1-naphthyl, 2- Η-propylcarbonoxy-1-naphthyl, 2-i-propylcarbonoxy-1-naphthyl, 2-η-butylcarbenyloxy-1-naphthyl' 2-i- Butylcarbonoxy-1-naphthyl, 2-s-butylcarbenyloxy-1-naphthyl, 2-t-butylcarbenyloxy-1-naphthyl, 2-phenyl-1 -naphthyl, 2-(2-fluorophenyl)-1-naphthyl, 2-( 2-Chlorophenyl)-1-naphthyl, 2·(2-bromophenyl)-1-naphthyl, 2-(2-iodophenyl)-1-naphthyl, 2-(2-methylbenzene 1-naphthyl, 2-(2-methylphenyl)-1-naphthyl, 2-(3-methylphenyl)-1-naphthyl, 2-(4-methylphenyl) 1-naphthyl, 2-(3,5-dimethylphenyl)-1-naphthyl, 2-(2-methoxyphenyl)-1-naphthyl, 2-(3-methoxy Phenyl)-1-naphthyl, 2-(4-methoxyphenyl)-1-naphthyl, 2-(3,5-dimethoxyphenyl)-1-naphthyl, 2-(〇 -biphenyl)-1-naphthyl, 2-(m-biphenyl)-1-caiyl, 2-(p-biphenyl)-1-nyl, 2-[p-(t-butyl) Dimethyl decyl)phenyl]-1-naphthyl, 2-benzyloxy-1-naphthyl, 6-indol-1-nyl, 6-indol-2-nyl, 6-di-2 -methyl-1-naphthyl, 6-bromo-2-trifluoromethyl-1-naphthyl, 6-bromo-2-ethyl-1-naphthyl, 6-bromo-2-pentafluoroethyl-1 -naphthyl, 6-bromo-2-n-propyl-1-naphthyl, 6-bromo-2-i-propyl-1-naphthyl, 6-diose-2-seven-n-propyl- 1-Caiji, 6-Xi-2-qiqi-i-propyl-1-caiji, 6-mo- 2- 2-n-butyl-1-nyl, 6-di- 2- i-butyl -1-naphthyl, 6-di- 2- s-butyl-1-naphthyl, 6-bromo-2-t-butyl-1-naphthyl, 6-bromo- 2-nonafluoro-n-butyl-1-naphthyl, 6-bromo-2-nonafluoro-t-butyl-1-naphthyl, 6-bromo-2-methoxy-1-nyl, 6 -Moly-2-ethoxy-1-nyl, 6-di- 2- i-propoxy-1-nyl, 6-bromo-2-n-butoxy-1-naphthyl, 6- Bromo-2-n-butoxy-1-naphthyl, 6-di-2- s-butoxy-1-nyl, 6-di- 2-t-butoxy-1-nyl, 6 -Moistence 2-methylcarbenyloxy-p-naphthyl, 6-bromo-2-ethylcarbenyloxy-1-naphthyl, -24- 201002659 6 -Moisture - 2-n-propyl carbon oxy -1-naphthyl, 6-moly- 2- i-propyl 1-naphthyl, 6-bromo-2-n-butylcarbenyloxy-p-naphthyl, 6-bromo-acidoxy-1-naphthyl , 6 - desert - 2- s-butyl carbon, oxy-1-cainyl t-butylcarbenyloxy-1-naphthyl, 6-bromo-2-phenyl-1-naphthyl, 3- Bromophenyl)-1-naphthyl, 6-bromo-2-[2-methylphenyl]-1 bromo-2-(3-methylphenyl)-1-naphthyl, 6-bromo-2- (4-methylnaphthyl, 6-bromo-2-(3,5-dimethylphenyl)-1-naphthyl, 6-goxyphenyl)-p-naphthyl, 6-bromo-2-(3 -Methoxyphenyl) 6-bromo-2-(4-methoxyphenyl)-1-naphthyl, 6-bromo-2-(3,5 phenyl)-1-naphthyl, 6-bromo - 2-(o-biphenyl)-1-naphthyl, m_biphenyl)- 1-naphthyl, 6-bromo-2-(p-biphenyl)-1-naphthalene 2-[p-(t-butyl-methyl-indolyl)phenyl]-1-inyl, oxygen -1 -naphthyl, 6-iodo-1-naphthyl, 6-iodo-2-naphthyl, 6-iodo-2-methyl-1 iodo-2-trifluoromethyl-1-naphthyl, 6 -iodo-2-ethyl-1-naphthyl, 6 ethyl-1-naphthyl, 6-iodo-2-n-propyl-1-naphthyl, 6-iodo-2-i-yl, 6-碑-2-七气- η-propyl-1-nyl, 6-exchange-2-hepta-i, 6-iodo· 2 - η-butyl-1 -naphthyl, 6-iodo-2 - i - butyl-; 1-naphthalene 2-s-butyl-1-naphthyl, 6-iodo-2_t-butyl-p-naphthyl, 6-iodobutyl-1-naphthyl, 6-iodo-2- Nonafluoro-t-butyl-1-naphthyl, 6-yl-1-naphthyl, 6-iodo-2-ethoxy-1-naphthyl, 6-iodo-2-i-propyl, 6- Iodo-2-n-butoxy-1-naphthyl, 6-iodo-2-i-butoxy 6-iodo-2-s-butoxy-1-naphthyl, 6-iodo-2-t -butoxy-1-naphthalene 2-methylcarbenyloxy-1-naphthyl, 6-iodo-2-ethylcarbenyloxycarbenyloxy-2-i-butyl carbon; Bromo-2-6-indi-2-(-naphthyl, 6-phenyl)-1-b 2-(2-methyl-1-naphthyl, dimethoxy-6-indi-2-(yl, 6 -Moly-6-bromo-2-benzyl-naphthyl, 6-- sure-2-pentafluoro-propyl-1-naphthalenyl-propyl-1-naphthyl, 6-砸_-2 -nonafluoro-n-iodo-2-methoxyoxy-1-naphthalene-1-naphthyl, benzyl, 6-yao--1-naphthyl, -25- 201002659 6-iodo-2-n-propyl Carboxyoxy-i-naphthyl, 6-iodo-2-i-propylcarbenyloxy-1- 1-naphthyl, 6-iodo-2-n-butylcarbenyloxy-nonyl-naphthyl, 6. Iodine-2_i_butylcarbenyloxy-1-naphthyl, 6-iodo-2-s-butoxycarbonyloxy-1-naphthyl, 6-捵_2_t-butyl carbonate-based 1-Nyliden, 6-trace_2·phenyl-1-caiyl, 6-suo-2-(3-bromophenyl)-1-naphthyl, 6-iodo-2-(2-methylbenzene 1-naphthyl, 6-iodo-2-(3-methylphenyl)-1_naphthyl, 6-iodo-2-(4-methylphenyl)naphthyl, 6-iodo- 2- (3,5-Dimethylphenyl)-1-naphthyl '6-iodo-2-(2-methoxyphenyl)-1-naphthyl, 6-iodo-2-(3-methoxy Phenyl)-1-naphthyl, 6-iodo-2-M-methoxyphenyl)-1-naphthyl, 6-iodo-2-(3,5-dimethoxyphenyl)-1-naphthalene 6, 6-捵- 2-(〇-biphenyl)-1-naphthyl, 6-iodo-2-( m-biphenyl)-1-naphthyl, 6-iodo-2-(p-linked Phenyl)-1-naphthyl, 6_shuo_2-[p-(t-butyldimethylmethylalkyl)phenyl]-anthracene-naphthyl, 6-iodo-2-ethoxyl-1 Naphthyl and the like. In the above formula (1) and formula (2), R1 is preferably a hydrogen atom or a phenyl group (the group is unsubstituted or is Cl-4 fluorenyl, Ci_4 dentate, Ci_4 oxy, <^_4 Alkyl carboxyoxy, C6., 2 aryl (the aryl group is unsubstituted or is selected by Ci-4 alkyl, (^_4_alkyl and C!-4 alkoxy the same or different) One or more substituents are substituted), C6-22 aryl methoxy (the aryl methoxy group is unsubstituted or selected by Cu olefin, C 1-4 alkoxy group, halogen atom and phenyl group) Or one or more substituents substituted with one or more substituents) and one or more substituents selected from the same or different halogen atoms, or a naphthyl group (the naphthyl group is unsubstituted) or is substituted by Ci-4, Ci- 4 halogen-based, Ci-4, oxy, C! alkyl carboxyoxy, C6.22 aryl (the aryl group is unsubstituted, or is Ci.4 alkyl, (^.4 haloalkyl) Among the Ci-4 alkoxy groups, one or more substituents of the same or different -26-201002659 are selected, S m ^ , y) t-butyl monomethyl decyl, C 6-22 aryl methoxy (the aryl) The methoxy alkoxy fluorenyl group is unsubstituted or is selected by C 丨 4 alkyl group, Cu: extraction, tooth atom and phenyl group. One or more of the same or different ones are selected from the same or different ones or more than one or more of the substituents are optically active or optically inactive. One-to-one (1) and (2) Wherein R1 is again a hydrogen atom, a phenyl group, a fluoro-phenylphenyl group, a 2-pentafluoroethylphenyl group, a 2-benzyloxy-2-methyl group, a 2 phenyl group, a phenyl group, a 2-(3_A group) Phenyloxy)phenyl, 2-(4-yloxy)phenyl, 2-(2,4,6-tri-i-propylbenzyloxy)phenyl, 2- 2-fluorobenzyloxy)benzene , 2-(3-fluorobenzyloxy)phenyl, 2 methoxy)phenyl, octa(2-bromobenzyloxy)phenyl, 2)phenyl-[j /旲卞%]_ 2- (4-bromobenzyloxy) benzyl, 2·(2-methoxybenzyloxy) benzyl 2, (3-methoxybenzyloxy)phenyl, 2-(4-methoxybenzyl) Benzene! ^ Anthracene, 2-methoxyphenyl, 2-(9-fluorenylmethoxy)phenyl, 1_fluorenylmethoxy)phenyl, 2-mercaptomethoxyphenyl, 2_(2 _Naphthyloxy)phenyl, 2-(2-biphenylmethoxy)phenyl, 2-ethoxybenzene, 2μ'-didecylphenyl, 2-η-butoxyphenyl, 2 _Phenyl-丨-naphthylmethoxy-indolyl group is preferred. In the above formula (1) and formula (2), R is more preferably a hydrogen atom, methyl benzoquinone, 2-benzyloxyphenyl, 2-(4-methylbenzyloxy)phenyl, 4 (2, 4). ,6-Hi-propylbenzyloxy)phenyl, 2-(octafluorobenzyloxy)phenyl' 2_(2,bromobenzyloxy)phenyl, 2-(2-methoxybenzyloxy) Benzene, 2-methoxyphenyl, 2-(9-fluorenylmethoxy)phenyl, benzyl-based 2'(2.naphthylmethoxy)-based, 2-(2·linked Phenylmethoxy (4-gas -27-201002659 phenyl, 2-phenyl-1-naphthyl, 2-methoxy-1-naphthyl. R2 in the above formula (1) and formula (2) It is a hydrogen atom, a halogen atom, a Ch4 or a Cl.4 halogen. The R2 in the above formula (1) and formula (2) will be specifically described below. The halogen atom is, for example, a fluorine atom, a chlorine atom or a bromine atom. Iodine atom, the alkyl group such as methyl, ethyl, η-propyl, i-propyl, η-butyl, i-butyl, s-butyl, t-butyl, etc. The Ch4 haloalkyl group For example, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, chlorofluoromethyl, dichloromethyl, bromofluoromethyl, trifluoromethyl, chlorodifluoromethyl, Chlorofluoromethyl, trichloromethyl, bromodifluoromethyl, bromine Chlorofluoromethyl, dibromofluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2,2-difluoroethyl, 2-chloro-2-fluoroethyl, 2, 2-Dichloroethyl, 2-bromo-2-fluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2- Fluoroethyl, 2,2,2-trichloroethyl, 2-bromo-2,2-difluoroethyl, 2-bromo-2-chloro-2-fluoroethyl, 2-bromo-2,2- Dichloroethyl, 1,1,2,2-tetrafluoroethyl, pentafluoroethyl, 1-chloro-1,2,2,2-tetrafluoroethyl, 2-chloro-1,1,2, 2-tetrafluoroethyl, 1,2-dichloro-1,2,2-trifluoroethyl, 2-bromo-1,1,2,2-tetrafluoroethyl, 2-fluoropropyl, 2- Chloropropyl, 2-bromopropyl, 2-chloro-2-fluoropropyl, 2,3-dichloropropyl, 2-bromo-3-fluoropropyl, 3-bromo-2-chloropropyl, 2 ,3-dibromopropyl, 3,3,3-trifluoropropyl, 3-bromo-3,3-difluoropropyl, 2,2,3,3-tetrafluoropropyl, 2-chloro-3 ,3,3-trifluoropropyl, 2,2,3,3,3-pentafluoropropyl, 1,1,2,3,3,3-hexafluoropropyl, heptafluoropropyl, 2,3 -dichloro-1,1,2,3,3-pentafluoropropyl, 2-fluoro-1-methylethyl, 2-chloro-1-methylethyl, 2-bromo-1-methyl Base, 2,2,2-trifluoro-1-(trifluoromethyl)ethyl, 1,2,2,2-tetrafluoro-1-(trifluoromethyl) , 2,2,3,3,4,4-hexafluorobutyl-28- 201002659 , 2,2,3,4,4,4-hexafluorobutyl, 2,2,3,3,4,4 ,4-heptafluorobutyl, 1,1,2,2,3,3,4,4-octafluorobutyl, nonafluorobutyl, 4-chloro-1,1,2,2,3,3, 4,4-octafluorobutyl, 2-fluoro-2-methylpropyl, 2-chloro-1,1-dimethylethyl and 2-bromo-1,1-dimethylethyl. R2 in the above formula (1) and formula (2) is preferably a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, an η-propyl group, an i-propyl group or a η-butyl group. , t-butyl, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, chlorofluoromethyl, trifluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, bromine Difluoromethyl, bromochlorofluoromethyl, dibromofluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2,2-difluoroethyl, 2-chloro-2- Fluoroethyl, 2-bromo-2-fluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl , 2-bromo-2,2-difluoroethyl, 2-bromo-2-chloro-2-fluoroethyl, 1,1,2,2-tetrafluoroethyl, pentafluoroethyl. R2 in the above formula (1) and formula (2) is more preferably 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 or a trifluoromethyl group. , pentafluoroethyl. In the above formulas (1) and (2), R3 and R4 each independently represent a hydrogen atom, a halogen atom, a Cm alkyl group, (^_4 haloalkyl group, Cm alkoxy group, C6.12 aryl group, C6-12 squarium oxygen). The nitro group and the aryl group. Hereinafter, R3 and R4 in the above formula (1) and formula (2) will be specifically described. The halogen atom is, for example, a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. Alkyl such as methyl, ethyl, η-propyl, i-propyl, η-butyl, i-butyl, S-butyl, t-butyl%=. The Ci-4 _ ^Gas methyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, chlorofluoromethyl, dichloromethyl, -29- 201002659 bromofluoromethyl, trifluoromethyl, chlorodifluoro Base, dichlorofluoromethyl, trichloromethyl, bromodifluoromethyl, bromochlorofluoromethyl, dibromofluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2 ,2-difluoroethyl, 2-chloro-2-fluoroethyl, 2.2-dichloroethyl, 2-bromo-2-fluoroethyl, 2,2,2-trifluoroethyl, 2-chloro- 2.2-Difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, 2-bromo-2,2-difluoroethyl, 2-bromo-2- Chloro-2-fluoroethyl, 2-bromo-2,2-dichloroethyl, 1,1,2,2-tetrafluoroethyl, pentafluoro Ethyl, 1-chloro-1,2,2,2-tetrafluoroethyl, 2-chloro-1,1,2,2-tetrafluoroethyl, 1,2-dichloro-1,2,2- Trifluoroethyl, 2-bromo-1,1,2,2-tetrafluoroethyl, 2-fluoropropyl, 2-chloropropyl, 2-bromopropyl, 2-chloro-2-fluoropropyl, 2,3-dichloropropyl, 2-bromo-3-fluoropropyl, 3-bromo-2-chloropropyl, 2,3-dibromopropyl, 3,3,3-trifluoropropyl, 3 -Bromo-3,3-difluoropropyl, 2,2,3,3-tetrafluoropropyl, 2-chloro-3,3,3-trifluoropropyl, 2,2,3,3,3- Pentafluoropropyl, 1,1,2,3,3,3-hexafluoropropyl, heptafluoropropyl, 2,3-dichloro-1,1,2,3,3-pentafluoropropyl, 2 -Fluoro-1_methylethyl, 2-chloro-1-methylethyl, 2-bromo-1-methylethyl, 2,2,2-trifluoro-1-(trifluoromethyl)B Base, 1.2.2.2-tetrafluoro-1-(trifluoromethyl)ethyl, 2,2,3,3,4,4-hexafluorobutyl, 2,2,3,4,4,4-hexa Fluorobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, 1,1,2,2,3,3,4,4-octafluorobutyl, nonafluorobutyl, 4 -Chlorine-1,1,2,2,3,3,4,4-octafluorobutyl, 2-fluoro-2-methylpropyl, 2-chloro-1,1-dimethylethyl and 2 -Bromo-1,1-dimethylethyl, etc. The Ci.4 alkoxy group, such as methoxy, ethoxy, η-propoxy, i-propoxy, η-butoxy, i -butoxy, s-butyl Group, T-butoxy group, etc. The C6-12 aryl group such as phenyl, 1-naphthyl, 2-naphthyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl and the like. The C6.12 aryloxy group, such as phenoxy, 1-naphthyloxy, 2-naphthyloxy, 2-biphenyloxy, 3-biphenyloxy, -30-201002659 4-biphenyloxy, etc. . In the above formulas (1) and (2), R3 and R4 are preferably a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a methyl group, an ethyl group, an η-propyl group, an i-propyl group or a η-butyl group. I-butyl, s-butyl, t-butyl, trifluoromethyl, pentafluoroethyl, methoxy, ethoxy, η-propoxy, i-propoxy, η-butoxy , i-butoxy, s-butoxy, t-butoxy, phenyl, 1-naphthyl, 2-naphthyl, phenoxy. R3 and R4 in the above formula (1) and formula (2) are more preferably 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 or a trifluoro group. Methyl, methoxy, ethoxy, i-propoxy, t-butoxy fluorene Specifically, in the above formulas (1) and (2), R2 and R3 together form - CR5 = CR6-CR7 = CR8-, R5 and R7 are the same as R3 and R4 above. Partial construction - CR5 = CR6-CR7 = CR8 - medium part structure - CR5 = equivalent to R2, partial structure - CR8 = equivalent to R3. Specifically, in the above formulas (1) and (2), when R2 and R3 together form -CR5 = CR6-CR7 = CR8-, R6 is the same as the above R2. In the above formulas (1) and (2), R2 and R3 together form -CR5 = CR6-CR7 = CR8-, and R8 is a gas atom or a halogen atom. When R6 is specifically described, the halogen atom is a fluorine atom or a chlorine atom. , bromine atom, iodine atom. R8 is preferably a hydrogen atom or a fluorine atom. In the above formulas (1) and (2), when R2 and R3 together form -CR5 = CR6-CR7 = CR8-, R5 and R7 are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom or an iodine. Atom, methyl, ethyl, i-propyl-31 - 201002659 _ fluoromethyl, methoxy, ethoxy, i-propoxy or t-butoxy A is preferably a hydrogen atom or a fluorine atom. , chlorine atom, bromine atom, iodine atom, methyl, ethyl, propyl t-butyl, trifluoromethyl or pentafluoroethyl. R, r2, r3 and r4 are each independently substituted into three phenyl groups (the phenyl group is unsubstituted or substituted by a certain A + substituent A and one or more substituents selected from the same or different hydroxyl groups)彳# a ~r ^ , substituted) substituted, and can be used in q·4 alkyl and halogen atoms

The Ci 4 alkyl group substituted by one or more substituents, which is substituted by one or more phases, is one to three phenyl groups (the phenyl group is unsubstituted, Or substituted by a substituent A and a radial group: a phenyl group substituted with the same or different substituents substituted by more than one substituent, a phenylcarbenium group which is unsubstituted, and a substituent A and a hydroxyl group. The same or more than one or more substituents are selected to be substituted, phenyl fluorenyl (the phenyl sulfonyl group is unsubstituted, or is selected by the substituent A and the same or different in the radial group; Substituted), preferably constructed as follows: Π), (Π), (out), (Μ, Μ, and (V1) ' [化7] + _ •R"

(1) (Hi) (iv) (Η) In the structure selected in (vi), part of the structure of 'Rl, R2, R3, and r4, and the three of which are independently represented by the formula (:!) of the substituent A, A polynuclear phenol compound having 2 to 3 bond structures held at any one of R1, R2, V and R4. The bonding positions of the bonded phenyl groups may be the same or different. 1 (i) where m is an integer of 2 or 3. -32- 201002659 The structures represented by formulas (i), (ii) and (iii) are better as in (i), (ii), (iii), (iv), (v) and (vi). m in the formula (i) is preferably 2. R11 in the formula (i) is, for example, a hydrogen atom, a halogen atom, a C?-4 alkyl group or a C,.4 haloalkyl group or the like. R11 in the above formula (i) will be specifically described below. The Ci.4 hospital base is such as methyl, ethyl, η-propyl, n-butyl and the like. The Cl_4 haloalkyl group is fluoromethyl, chloromethyl, bromomethyl, iodomethyl, trifluoromethyl, pentafluoroethyl or the like. R11 in the above formula (i) is preferably a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an atom, a methyl group, an ethyl group, an η-propyl group, an i-propyl group, an η-butyl group or a trifluoromethyl group. , pentafluoroethyl. R11 in the above formula (i) is more preferably a hydrogen atom, a fluorine atom, a methyl group or a trifluoromethyl group. Hereinafter, each substituent in the above formula (a) representing an amine compound for a plurality of ligands will be explained. In the above formula (a), the rule 9 is a Cm alkyl group, or two R9 on the same nitrogen atom together form =CH-R1(). R9 in the formula (a) will be specifically described below. The d_3 fluorenyl group is, for example, a methyl group, an ethyl group, an η-propyl group, an i-propyl group or the like. R9 in the above formula (a) is preferably a methyl group or an ethyl group. When two R9 on the same nitrogen atom in the above formula (a) are formed together = CH_R1Q, 'R1CI is a Cbn aryl group (the aryl group is unsubstituted, or is halogenated by a halogen atom, Cl.4, and Cl.4). One or more substituents of the same or the target are substituted in the base). -33- 201002659 Next, R1() when two R9 on the same nitrogen atom in the above formula (a) is formed together with =CH-R1() will be specifically described. The C6.12 aryl group is phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromobenzene. , 3-bromophenyl, 4-bromophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4 -ethylphenyl, 2-n-propylphenyl, 2-i-propylphenyl, 2-n-butylphenyl, 2-i-butylphenyl, 2-s-butylphenyl , 2-t-butylphenyl, 2,6-dimethylphenyl, 2,6-dipropylmethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4- Methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-n-propoxyphenyl, 2-i-propoxyphenyl, 2-n-butoxyphenyl, 2-i-butoxy-based, 2-s-butoxy-based, 2-t-butoxy-based, 2,6-dimethoxyphenyl, 2, 6-Dipropoxymethoxyphenyl, 1-naphthyl, 2-naphthyl, anthracene-biphenyl, m-biphenyl, p-biphenyl, and the like. When two R9 on the same nitrogen atom in the above formula (a) form a =CH-R1(), R1() is preferably a phenyl '2-fluorophenyl group, a 2-bromophenyl group or a 2-methyl group. Phenyl, 2-ethylphenyl, 2-methoxyphenyl, 2-i-propoxyphenyl. When two R9 on the same nitrogen atom in the above formula (a) form =C Η-R1(), R1() is more preferably phenyl, 2-fluorophenyl, 2-methylphenyl, 2- Methoxyphenyl, 2-i-propoxyphenyl. The amine compound represented by the above formula (a) is preferably ruthenium, osmium, iridium, Ν'-tetramethylethylidene diamine. ^,>4,',>^",>^"-pentamethyldiethylideneamine, the preferred amine compound is hydrazine, hydrazine, hydrazine, Ν'-tetramethylexylethyl amine. Most of the amine compounds for the plurality of ligands represented by the above formula (a) can be obtained from a reagent. Further, an unsold amine compound can be produced by the following method -34-201002659. The amine compound of the formula (a) wherein n = 2 can be produced by the method described in J. 〇rg. Chem_ (1987) '52 Vol. 2571-2576. (Reaction formula 1) is as follows. Nh2 + hcho hco2h h2o i (Reaction formula 1) Synthesis of two R9 on the same nitrogen atom of formula (a) to form an amine compound = CH-R1() For example, 'by Tetrahedron Letters (1990) , Volume 31, 451-454. Manufactured by the method described on page 452. (Reaction formula 2) is as follows. [Chemistry 9]

+ PhCHO

MgS04

Et20 (Reaction formula 2) The foregoing method 11 described above is a method in which a composition of magnesium chloride and triethylamine is reacted using a paraformaldehyde to form a wake-up compound from a aryl group-based compound (Non-Patent Document 17 and Non-Patents). Document 18), which can efficiently and positionally introduce a formazan group to carry out a 2-hydroxyaryl aldehyde compound reaction. Organic Synthesis, (2005) 82, 64-67. Only the compound which imparts the hydroxyaryl compound of the formazan to the ortho position and which does not impart the bis-carbamidine is described by the inventors of the present invention, and it is confirmed that the compound of the amidoformin which is described cannot be formed by the reaction, and A by-product of unknown construction is generated. Further examination of this by-product revealed that the by-product was inhibited by substituting an amine compound for a plurality of ligands for the amine for the reaction. In the following description, the comparative example is described in the section -35-201002659. Next, a method for producing a 2-hydroxyaryl aldehyde compound as a single core will be explained. After nitrogen substitution of the flask equipped with the stirring machine and the reflux tube, 1 to 4 moles (preferably 1.5 to 3 moles) of magnesium chloride, and 1 to 8 moles, relative to the starting hydroxyaryl compound are added. The (or preferably 1.5 to 4 moles) of the paraformaldehyde' and the organic solvent (the concentration is not particularly limited, preferably 0.05 to 2.0 m/L) are stirred. The organic solvent used for the reaction is preferably a nitrile solvent, an ether solvent or dimethyl hydrazine. The nitrile solvent is, for example, acetonitrile, propionitrile, butyronitrile, isobutyronitrile or the like. Preferred are acetonitrile and propionitrile. The ether solvent is, for example, 'dioxane, t-butyl methyl ether, c-pentyl methyl ether, tetrahydrofuran, diethyl ether or the like. Preferred are dioxane and tetrahydrofuran. The temperature of the reaction solution at this stage is not particularly limited, and is preferably from 15 to 1 20 ° C below the boiling point temperature of the solvent above the boiling point of the solvent. Next, an amine compound of 0.1 to 4 moles (preferably 0.2 to 3 moles) is added to the hydroxyaryl compound of the starting material, and the starting hydroxyaryl group (1 mole) is dissolved or suspended in the organic compound. A solution obtained by using a solvent (the organic solvent type is as described above) is added to the reaction solution. Further, only the hydroxyaryl group of the starting material may be added to the reaction solution. The reaction temperature is preferably from 55 to 120 ° C, more preferably from 60 to i 〇 (TC. The reaction time is not particularly limited, and the reaction conversion rate can be checked and appropriately selected. After the reaction is completed, it is cooled to 10 to 30 ° C. The reaction is quenched by using diluted hydrochloric acid prepared to a concentration of 1 to 4 mol/L. The liquid is subjected to liquid separation and re-extraction, and the solvent is distilled off to obtain a crude product. The method for purifying the crude product is not particularly limited, and the 2-hydroxy aryl group can be used depending on the purpose. The aldehyde compound may be appropriately selected. The purification method may be sublimation purification, column color-36-201002659 spectrum purification, or purification by crystallization operation-filtration operation, etc. The following describes the 2-hydroxyaryl aldehyde compound as a multi-nuclear. The phenolic hydroxyl number of the starting material used for the preparation. When it is a dinuclear hydroxyaryl compound, it is 2 to 8 moles (preferably 3, and the secondary formaldehyde is 2 to 16 moles) relative to the magnesium chloride of the starting aryl compound. (preferably 3 to 8 moles of 〇_2 to 8 moles (preferably 0.4 to 6 moles). The hydroxyaryl compound is 3 to 12 moles relative to the starting hydroxyaromatic magnesium chloride ( Preferably 4 to 5 to 9 moles are 3 to 24 moles (preferably 4.5 to 12) Ears, 0.3 to 12 moles (preferably 0.6 to 9 moles). Method for producing other mononuclear 2-hydroxyaryl aldehyde compounds. [Embodiment] Hereinafter, the present invention will be described in more detail by way of examples, but Non-Example (Hydroxyaryl compound of starting material for synthesis) 2'-(Phenylmethoxy)-, [!'-biphenyl-2-alcohol (Organic & Biomolecular Chemistry (2006) 3639_3647. The method of the invention is as follows. The synthesis method is as follows: (reversely, the production method is a reagent for the amount of the hydroxyl group of the raw material to 6 mol), and the amine compound is a trinuclear compound), and the paraformaldehyde compound is operated as described above. When the case 5) can be based on 4 (19), the volume should be 3) -37- 201002659

The synthesis of 2'-methoxy-1,1'-biphenyl-2-ol (8) can be carried out according to Tetrahedron Letters (2002), Volume 43, 9327-9329. The method described is manufactured. The synthesis method is as shown in (Reaction formula 4). [化11]

(6) K2C〇3 acetone

(Reaction formula 4) (Synthesis of hydroxyaryl aldehyde compound) Example 1 Synthesis method of 2-hydroxy-2'-(phenylmethoxy)biphenyl-3-carbaldehyde (9) and (Reaction formula 5) are as follows Shown.

(Reaction formula 5) [Chem. 12]

(5)

MgCip (CH20)n / \ _N N- N_/

Amine compound THF After nitrogen substitution of a flask equipped with a stirring machine and a reflux tube, magnesium chloride (〇-69g, 7_2 mmol), argon (0.33 g, 11 mmol) -38-201002659, tetrahydrofuran (l〇mL) was added. , then take 26 to 30. (: stirring. Next, add N, N, N', N'-tetramethylethylidene diamine (0.84g' 7.2 mmol) of the amine compound and then the hydroxyaryl compound (5) (l.Og, 3.6 mmol) A solution of tetrahydrofuran (1 mL) was added to the reaction solution. The reaction was stirred at a reaction temperature of 64 to 66 ° C for 21 hours. After the reaction, it was cooled to 15 to 20 ° C, and then adjusted to 2.5 mol. /L diluted hydrochloric acid to quench the reaction, and the organic layer was separated, and the organic layer was extracted with tetrahydrofuran, and the solvent was evaporated to give a crude product, which was purified by column chromatography to give a pale yellow oily compound. 2-hydroxyaryl aldehyde compound (9 ) (0 _ 8 8 g, yield 80%, chemical purity 9 9.5 %). Η PLC analysis conditions: column name Gemini 5 u C 1 8 110A (manufactured by phenomenex), Dissolution liquid acetonitrile / water / acetic acid = 600/400/1 (v / v / v), flow rate 1 · 0 mL / min, column temperature 40 ° C, measurement wavelength 23 0nm 〇 ^-NMR ( 3 00MHz > CDC13 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 to 7.59 (m, 2H, Ar) 9.94 (s, ih, CHO), 11.36 (s, 1H, OH). Example 2 2-Phenyl-2'-methoxy-1,1'-biphenyl-3-carbohydrazide (i〇) The synthesis method and (Reaction Formula 6) are as follows. -39- 201002659 [Chem. 13]

MgCb (CH20)n / \ a N N- \_/ amine compound Dic UIC

CHO

OH (Reaction formula 6) (8) (10) After nitrogen substitution of a flask equipped with a stirring machine and a reflux tube, magnesium chloride (2.9 g '30 mmol), paraformaldehyde (i_4g, 45 mmol), tetrahydrofuran (30 mL) was added. Then, stir at 24 to 27 °C. Next, an amine compound, Ν, Ν', Ν'· tetramethyl-ethylidene diamine (3.5 g > 30 mmol), and a hydroxyaryl compound (8) (3.0 g, i5 mm ο 1 ) were added. A solution dissolved in tetrahydrofuran (3.4 m L ) was added to the reaction solution. The reaction was carried out by stirring at a reaction temperature of 64 to 66 t for 20 hours. After the completion of the reaction, the mixture was cooled to 15 to 20 ° C, and the reaction was quenched with a diluted hydrochloric acid of 2.5 mol/L. After the organic layer was separated, the organic layer was extracted with tetrahydrofuran and the solvent was evaporated to give a crude product. Things. Subsequently, it was purified by column chromatography to give the title compound 2-hydroxy aryl aldehyde compound (10) ( 2.88 g, yield: 84%, chemical purity: 97%). HPLC analysis conditions: column name Gemini 5 u C 1 8 110A (manufactured by phenomenex), dissolvent acetonitrile / water / acetic acid two 600 / 400 / 1 (v / v / v), flow rate 1 · 〇 mL / min, column temperature 4 (TC, measurement wavelength 2 5 4 nm 〇*H-NMR (3 00 MHz > CDC13) δ ; 3.79 ( s, 3H, OCH 3 ), 7_00 to 7.10 (m, 3H, Ar) , 7_25 to 7.41 (m, 2H , Ar -40 - 201002659 ), 7.53 ~ 7.58 ( m, 2H, Ar ) , 9.94 ( s, 1 1 .29 ( s, 1 Η, OH ). Example 3 2 hydroxy-2'-methoxy- oxime , ι'_biphenyl-3·carbonaldehyde (! For the flask equipped with a stirring machine and a reflux tube, magnesium nitrate (52g, 0.55 mol), paraformaldehyde (25g, tetrahydrofuran (495mL)' and then 63 to 66 °C The solution of S, followed by the addition of the amine compound N, N, N', N'-tetramethyl 64g, 0.55 mol) 'and the hydroxyaryl compound mol) to tetrahydrofuran (93 mL) was added to the reaction temperature 64. After stirring at 66 ° C for 12 hours to carry out the reaction solution, the mixture of the target product (10) was subjected to the edge analysis by H p L c analysis to determine the conversion rate. The analysis conditions of the PLC: column name L -columnODS (chemical substance Price 硏 male solvent acetonitrile / water / acetic acid = 600 / 400/1 flow rate 1 · 〇m L / mi η, column temperature 4 0. (:, measured ο Table 1: Results of Example 3 1 Η, CHO) &gt ;) After the synthesis method is substituted, add 0.82 mol), I mix: Stretch ethyl diamine ( ) (55 g, 0.27 in the reaction solution.). Sampling part of the anti-hydroxyaryl aldolized fruit as shown in Table 1 Mechanism), (V/V/V), 疋 wavelength 230nm -41 - 201002659 [Table l] HPLC relative area percentage (%), 230 nm Reaction time (h) Starting material (8) Intermediate product (Note 1) By-product 1 byproduct 2 by-product total product of interest (10) 4 4.0 40.9 0.3 undetected 0.3 54.8 12 undetected 1.4 0.6 0.6 1.2 97.3 (Note 1) Inferred from the ortho position of the hydroxyl group in the starting hydroxyaryl compound (8) Hydrogen forms a compound via a methyl group. Comparative Example 1 Synthesis of 2-hydroxy-2'-methoxy-id,-biphenyl-3-carbaldehyde (1〇) Comparative Example 1 was replaced with triethylamine The N,N,N',N'-tetramethylethylidene diamine used in Example 3 was carried out. After nitrogen substitution in a flask equipped with a stirring machine and a reflux tube, 'addition of a chlorination table (3_8 g, 40 mmol), a secondary awake (1.8 g, 60 mmol), tetrahydrofuran (40 mL), and then at 63 to 66 ° C Stir. Next, an amine compound of triethylamine (4.0 g, 40 mmol) was added, and a solution of the 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 liquid was sampled, and the 2-hydroxyaryl aldehyde compound (10) of the desired product was subjected to a rim analysis by HPLC analysis to obtain a conversion ratio. The results are shown in Table 2 below. HPLC analysis conditions: column name L-column ODS (chemical substance evaluation research institution), dissolved solution acetonitrile / water / acetic acid = 600 / 400/1 (v / v / v), -42 - 201002659 flow rate 1.0 mL / min, column Temperature 40 ° C 'Measurement wavelength 23 0 nm Table 2 : Results of Comparative Example 1 [Table 2] HPLC relative area percentage (%), 230 nm Reaction time (h) Starting material (8) Intermediate product (Note 1) By-product 1 By-product 2 by-product total product of interest (10) 4 6.0 5.0 0.1 2.8 2.9 86.0 5 4.8 4.2 0.1 2.8 2.9 88.1 (Note 1): Inferred hydrogen in the ortho position of the hydroxyl group in the starting hydroxyaryl compound (8) A compound of methyl. Example 4 Synthesis of 3,3,-(1-methyl(ethylidene))bis(6-pyridylaldehyde) (12) of a dinuclear 2-hydroxyaryl aldehyde compound as shown in (Reaction formula 7) [14] (11)

MgCI2 (CH20)n / \ -N N- \_/ Amination

MeCN

(Reaction formula 7) After nitrogen substitution of a flask equipped with a stirring machine and a reflux tube, magnesium chloride (2.6 g, 27 mm )l), paraformaldehyde (! & 39 匪〇1), acetonitrile (20 mL) were added. Then disturb at 26 to 30 °C. Next, an amine compound of N, N, N, N,-tetramethylethylidene diamine (3.1 g, 26 mmol) was added, followed by a commercially available hydroxyaryl compound of 4,4,_ (_ -43- 201002659 Methyl ethylene) bisphenol (11) (I.5g' 6.6mmo1) was added to the reaction solution. The reaction was carried out by stirring at a reaction temperature of 7 8 to 81 ° C for 18 hours. After sampling a portion of the reaction solution, the conversion was determined by HPLC analysis and the result was 78%. After completion of the reaction, the mixture was cooled to 15 to 20 ° C. After the reaction was quenched by diluting hydrochloric acid with 2 mol / L, dichloromethane was added and the organic layer was separated. The aqueous layer was re-extracted with dichloromethane, and the organic layer was blended to remove the solvent to give a crude product. Then, it was purified by column chromatography to give a dinuclear 2-hydroxyaryl aldehyde compound (1 2 ) (1·4 g 'yield of 73 %) of the objective compound as a yellowish transparent oil. The resulting compound became a yellowish white solid after several hours. HPLC analysis conditions: column name Gemini 5u C18 110A (manufactured by phenomenex), dissolving solution acetonitrile / water / acetic acid = 600/400/1 (v/v/v), flow rate 1.0 mL / min, column temperature 40 ° C, Determination wavelength 2 30 nm 〇'H-NMR (300MHz, CDC13) δ; 1.71 ( s - 6H , CH3 ), 6.92 ( d ' J = 9.0Hz ' 2H, Ar ) , 7_35 ( dd, J = 9.〇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). Example 5 A method for synthesizing 2-hydroxy-2'-methoxy-1,1'-biphenyl-3-carbaldehyde (i) was carried out as follows (Reaction formula 8). -44- 201002659 [化15]

CHO OH

MgC!2 (CH20)n

(Reaction formula 8) After nitrogen substitution of a flask equipped with a stirring machine and a reflux tube, magnesium chloride (1.9 g, 20 mmol), paraformaldehyde (〇.90 g '30 mmol), tetrahydrofuran (18 g), 20 to 25 ° C were added. Stir. Next, add the commercially available amine compound, Ν, Ν', Ν'', Ν''-pentamethyldiethylidamine (2.3g, 20mmol), and then the aryl compound (8) (2.0 g, 10 mmol of a solution dissolved in tetrahydrofuran (2 g) was added to the reaction solution, and the reaction was carried out by stirring at a reaction temperature of 64 to 66 ° C for 30 hours. After sampling a part of the reaction solution, the conversion was determined by ΗPLC analysis and the result was 85%. HPLC analysis conditions: Column name L-column ODS (Chemical substance evaluation research institute), Dissolution liquid acetonitrile / water / acetic acid = 600 / 400 / l (v / v / v) ' Flow rate 1 · 0 mL / min, column temperature 4 0 ° C, measurement wavelength 23 0 nm 〇 Example 6 Synthesis of 2-hydroxy-2,-(9-fluorenylmethoxy)-1, fluorene biphenyl-3-carbaldehyde (23) as follows (Reaction formula 9 "TMEDA" is Ν,Ν,Ν',Ν'-tetramethylethylidene diamine. -45- 201002659 [Chem. 16] Deuterated alkyl compound

(6)

Magnesium chloride TMEDA paraformaldehyde acetonitrile

(Reaction formula 9) (Synthesis of hydroxyaryl compound) Synthesis of 2'-(9-fluorenylmethoxy)biphenyl-2-ol (22): 2,2-biguanide (4.10邑'22111111〇1) Cesium carbonate (3.04 Lu '2 2 mmol), potassium (3.66 g, 22 mmol) and acetone 26 mL were placed in a reaction vessel, and heated to 60 ° C in an oil bath with stirring. 9-Chloromethylhydrazine (21) (5.01 g, 22 mmol) was added to the suspension, and the mixture was stirred at 60 ° C for 20 hours, and the reaction conversion was confirmed by HPLC, and the reaction was stopped from a saturated aqueous solution of ammonium chloride. After liquid separation, the aqueous layer was extracted with ethyl acetate, and the mixture was concentrated to give a crude product. The crude product was purified by silica gel column chromatography to yield white crystals of hydroxy aryl compound (22) (3.01 g).

1H-NMR (300 MHz, CDC13) <5; 5.92 ( s, 2H OC Η 2 - ) ' 6.46 ( s' 1H ' -OH ) , 6.80 ( dd, J = 8.0 1.2 Hz, 1H ), 6.94 ( dt > J = 7.3 i > 1 , 2 Hz ; , 1 H ) , 7. 1 4 ~ 7.28 ( r η, 3H ) , 7.34 ~ 7.4 9 ( rn - 7H ), 7.93 ～ 8.03 ( rr , 2H ) , 8.03 ~ 8.13( m > 2 H ) -8.45 ( s , 1 H ). (Synthesis of hydroxyaryl aldehyde compound) -46- 201002659 Synthesis of 2-hydroxy-2'-(9-fluorenylmethoxy)n'-biphenyl-3_carbaldehyde (23): Paraformaldehyde (〇_72g) , 31 mmol), anhydrous magnesium chloride (i. 5g, 3 1 mmol), N, N, N', N'-tetramethylethylidene diamine (2.4 mL, 16 mmol) and acetonitrile (27 mL) were placed in a reaction vessel. The starting material (22) (3.0 g, 8 mmol) was added to the mixed solution while maintaining the temperature at 85 C, and then washed with acetonitrile (3.0 g). 85. (After stirring for 17 hours, the reaction was stopped by adding 2 mol/L hydrochloric acid. After neutralization, the acetonitrile was distilled off and the aqueous layer was extracted with ethyl acetate. The organic layer was washed three times with water (100 mL) and then evaporated. The crystals of the product were obtained as a pale brown crystal. The crystals of the crude product were washed with isopropyl alcohol to give a pale yellow powder of hydroxyaryl aldehyde (23 ) ( 1.86 g ) with a yield of 57.5% and a relative area fraction of HP LC of 89.2. %-NMR (3 00MHz > CDC13) <5; 5.90 ( s - 2H, -O- CH2- ) , 6.65 (t, J = 7.7Hz, 1 H ) , 7.08~7.20 (m, 2H) , 7.25 ~ 7_32 (m, 2H), 7.35 ~ 7.50 (m, 6H), 7_87 ~ 7.97 (m, 2H), 8.12 ~ 8_23 (m, 2H) ' 8.35 ( s - 1H ) , 9.64 (s, lH, -CHO), 11.15 (s, lH, -0H) HPLC analysis conditions: column name Inertsil ODS-3 4·6χ 1 50mmx3// m 'dissolve acetonitrile / 20 mM sodium acetate solution = 96/ 4 ( v / v ) , flow rate 1.0 mL / min, column temperature 4 〇 ° C, hold time 2 · 5 minutes, analysis wavelength 280 nm. -47- 201002659 Example 7 Synthesis of 2-hydroxy-2'-(4-methylbenzyloxy)- ΐ, ι'_biphenyl-3-carbaldehyde (3 3 ) is as described below (Reaction formula 10) [Chemical Formula 17] halogenated alkyl compound

(Synthesis of hydroxyaryl compounds) Synthesis of 2'-(4-methylbenzyloxy)biphenyl-2-ol (32): 2,2-bisphenol (3.72 Kun, 2〇111111〇1), potassium carbonate (1.38 §, 10 mmol), potassium iodide 3.72 g, 20 mmol) and acetone 23.5 mL were placed in a reaction vessel and heated to 6 Torr with an oil bath under stirring. (: p-Methylbenzyl chloride (31) (2.81 g, 20 mmol) was added dropwise to the suspension, and stirred at 60 ° C for 17 hours. After confirming the conversion of the reaction with HP LC, saturated chlorination was added. The ammonium aqueous solution was stopped, and the aqueous layer was extracted with ethyl acetate, and the mixture was combined and concentrated to give a crystals, which was purified by silica gel column chromatography (hexane / ethyl acetate = 9 / 1, Rf 値 = 0.25). Crystalline hydroxyaryl compound (32) (4.30 g), yield 74.0%. !H-NMR (3 00 MHz ' CDC13 ) δ ; 2.32 ( s ' 3H ' -CH3 ), 5.07 ( s - 2H, -OCH2 - ) , 6.4 1 ( s,1H ' -OH), 6.97~7.05(m,2H) ,7_07 〜7_19 ( m,6H) ' 7.23 〜 7.38 (m,4H). -48- 201002659 (Synthesis of hydroxyaryl Aldehyde compound) Synthesis of 2-hydroxy-2'-(4-methylbenzyloxy)-1, (33): Paraformaldehyde (0.93 g, 31 mmol), anhydrous in the case of 31 mmol) 'Ν, Ν, Ν', The temperature of Ν'-tetramethylethylenediamine 3.1 mL, 21 mmol) and tetrahydrofuran (30 mL) was maintained at 65 °C. The starting material (32) ( ) was put into the mixed solution, and stirred under tetrahydrofuran (3.0 g) for 17 hours. After adding 2 mol/L hydrochloric acid, the aqueous layer was extracted with tetrahydrofuran, and the organic layer was combined and concentrated to ethyl acetate. (200 mL), water (10 mL), and ethyl acetate was evaporated to give crystals of pale brown crystals, which crystallised to afford crystals of hydroxy aryl aldehyde (3 3 ) (yield 6 7.4 %. H-NMR (3 00MHz > CDC13) δ ; 2.31 ), 5.04 ( s, 2H, -〇CH2- ) , 7.01 ~ 7.12 7-13 ~ 7.18 ( m, 2H) , 7.29 ~ 7.37 ( m ' 7-59 (m, 4H) , 9 · 9 5 ( s, 1H, - CH 0 ), , -OH ). Example 8 Synthesis of 2-hydroxy-2'-methyl methoxybiphenyl as follows (Reaction formula 1 1 ) is recorded.

1 biphenyl-3-carbaldehyde magnesium (2.0 g, (TMEDA) (in the reaction vessel, 3.0 g » lOmmol after washing, 65 °C $ stop reaction. Dissolve ί. dissolve the concentrate) 3 After the second acetol suspension wash the 2.2 1 g), harvest (s, 3H, -CH3; (m, 5 Η) ' 2Η), 7.53 ~ 1 1.34 (s, 1H -3-carbaldehyde (43) -49 - 201002659 [Chemical 18] Halogenated alkyl compounds

Magnesium chloride TMEDA paraformaldehyde tetrahydrofuran

(Synthesis of a hydroxyaryl compound) Synthesis of 2'-mercaptomethoxy-1,1'-biphenyl-2-ol (42): 2,2-bisphenol (3.72 §, 2〇111111〇1), Potassium carbonate (2.76 §, 20 mmol), potassium iodide (3_32 g, 20 mmol) and acetone 24 mL were placed in a reaction vessel and heated to 60 ° C in an oil bath with stirring. 2,4,6-Trimethylbenzyl chloride (4 1 ) ( 3.37 g, 20 mmol) was added to the suspension, and stirred at 60 ° C for 17 hours. After confirming the conversion of the reaction by HPLC, the reaction was stopped by adding a saturated aqueous solution of ammonium chloride. After liquid separation, the aqueous layer was extracted with ethyl acetate, and then concentrated to give a crude product. The crude product was recrystallized from 2-propanol to give a white crystalline hydroxy aryl compound (42) (5.93 g). 'H-NMR (300MHz > CDC13) <5; 2.17 ( s > 6H - -CH3 )' 2.24 ( s 5 3H, - C Η 3 ) ' 5.01 ( s, 2H, - 0 C Η 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 to 7.43 (m, 2H). (Synthesis of a hydroxyaryl aldehyde compound) Synthesis of 2-carbyl-2'-propenylmethoxy-1,1'-biphenyl-3-carboprotein (43) -50- 201002659 Para-formaldehyde (〇.9〇) g, 30 mmol), anhydrous magnesium chloride (1.9 g, 20 mmol), N,N,N ',N '-tetramethylethylidene diamine (TM ED A ) (3.0 mL, 20 mmol) and tetrahydrofuran (32 mL) In the reaction vessel, the temperature was maintained at 65 °C. Starting material (42) (3.2 g, 10 mmol) was added to the mixed solution, washed with tetrahydrofuran (3.2 g), stirred at 701 for 17 hours, and then quenched by adding 2 mol/L hydrochloric acid. After the neutralization, the acetonitrile was evaporated and the aqueous layer was extracted with ethyl acetate. The organic layer was washed three times with water (100 mL), and then ethyl acetate was evaporated to yield crude product. The crude product was washed with isopropyl alcohol to afford white crystals of hydroxy aryl aldehyde (4 3 ) (1. 57 g). The yield was 45.4%, and the relative area fraction of HPLC was 99.2%. ^-NMR (3 00MHz > CDC13) δ ; 2.1 9 ( s,6 Η, - C Η 3 ), 2.21 ( s,3H > -CH3 ) ' 4.97 ( s ' 2H > -0-CH2-) ' 6_76 ( s, 2H ) , 6.94 ( t - J = 7.4 Hz, 1 H ) ' 6.75 ( td ' J = 7_3, 1.3 Hz, 1H) , 7.18 ~ 7.33 (m, 2H) > 7.35 ~ 7.49

(m > 3 H ) , 9_84 (s, 1H, -CHO), 11.21 (s' 1H, -OH ). HPLC analysis conditions: column name Inertsil ODS-3 4.6xl50mmx3# m, dissolving solution acetonitrile / 20 mM sodium acetate solution = 96/4 (v/v), flow rate 1.0 m L / min, column temperature 40 ° C 'maintained Time 2 _ 5 minutes' Analysis wavelength 2 5 4 nm. -51 - 201002659 Example 9 Synthesis of 2-hydroxy-2'-(2-naphthylmethoxy)-1,1'-biphenyl-3-carbaldehyde (5 3 ) as described below (Reaction formula 12) . Halogenated alkyl compound

(Synthesis of a hydroxyaryl compound) Synthesis of 2'-(2-naphthylmethoxy)-1,1'-biphenyl-2-ol (52): 2,2-bisphenol (3.7 g, 20 mmol), Potassium carbonate (2.8 g, 20 mmol) and acetone 24 mL were placed in a reaction vessel and heated to 60 ° C in an oil bath with stirring. 2-(Bromomethyl)naphthalene (51) (4.22 g > 20 mmol) was added to the suspension, and stirred at 60 ° C for 17 hours. After confirming the reaction conversion rate by HPLC, the reaction was stopped by adding a saturated aqueous ammonium chloride solution. After liquid separation, the aqueous layer was extracted with ethyl acetate, and then concentrated to give a crude product. The crude product was recrystallized from 2-propanol to give white crystals of hydroxy aryl compound (52) (4.75 g). *H-NMR (3 00MHz >CDC13); 5.26 (s,2H-OCH2-)> 6.3 1 (s > 1H, -OH), 6.97~7.08 (m, 2H), 7.08 to 7.18 (m , 2H), 7.25 ~ 7.41 (m, 5H), 7.41 ~ 7.50 (m, 2H), 7.67 ~ 7.84 (m, 4H). -52- 201002659 (Synthesis of hydroxyaryl aldehyde compounds) Synthesis of 2-hydroxy-2'-(2-naphthylmethoxy)-1,1'-biphenyl-3-carbaldehyde (53): 0.90 g, 30 mm 〇l), anhydrous magnesium chloride (1.9 g, 20 mmol), N,N,N',N'-tetramethylethylidene diamine (TMEDA) (3.0 mL, 20 mmol) and tetrahydrofuran (33 mL) ) Put into the reaction vessel and keep the temperature at 65 °C. The starting material (52) (3.26 g, 10 0. Ommo 1 ) was charged into the mixed solution, and washed with tetrahydrofuran (3.3 g). After stirring at 70 ° C for 15 hours, the reaction was stopped by adding 2 mol / L of hydrochloric acid. After the neutralization, the acetonitrile was evaporated and the aqueous layer was extracted with ethyl acetate. The organic layer was washed three times with water (1 〇 〇mL), and then ethyl acetate was evaporated to give a crude product. The crude product was washed with isopropyl alcohol to give a white crystals of hydroxy aryl aldehyde (53) (2.63 g), yield: 74.1%, and the relative area fraction of HPLC was 99.0%. ^-NMR (300MHz > CDC13) <5 ; 5 · 17 ( s, 2 Η, - 〇 _ C Η 2 * ) , 6.93 〜 7.08 ( m, 3H) , 7.25 〜 7.49 (m, 6H), 7.55 ( Dd » J = 7.4 > 1.8Hz » 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 4·6χ 1 50mmx3 // m, dissolving solution acetonitrile / 20 mM sodium acetate solution = 96/4 (v/v) flow rate 1.0 m L / min, column temperature 4 〇 ° C, Hold time 2 · 5 minutes, analysis wavelength 254nm. -53- 201002659 Example 1 Synthesis of 2-transyl-2'-(4-bromoprenyloxy)-1,1'-biphenyl_3_carbonase (6 3 ) as follows (Reaction formula 13) Documented. Halogenated alkyl compound

(Synthesis of hydroxyaryl compounds) Synthesis of 2'-(4-bromooctyloxy)-1,1'-biphenyl-2-ol (62): 2,2-bisphenol (3.72 Lu '2〇111111〇) 1) Potassium carbonate (2_76 ru, 20 mmol), potassium iodide (3.32 g, 20 mmol) and acetone 24 ml were placed in a reaction vessel, and heated to 60 ° C in an oil bath with stirring. 4-Bromobenzyl bromide (61) (4.99 g, 20 mmol) was added to the suspension, and stirred at 60 ° C for 17 hours. After confirming the conversion of the reaction with Η P L C, the reaction was stopped by adding a saturated aqueous solution of ammonium chloride. After liquid separation, the aqueous layer was extracted with ethyl acetate, and then concentrated to give a crude product. The crude product was recrystallized from 2-propanol to give a white crystals of hydroxy aryl compound (62) (4.78 g) with a yield of 67.3%. H-NMR (3 00MHz, CDC13) δ; 5.05 ( s, 2H, - 〇CH2-) , 6.11 (s, 1H, -0H), 6_97 -7 7 (19, m, 6H), 7.20 to 7.47 (m, 6H) . -54- 201002659 (Synthesis of hydroxyaryl aldehyde compound) Synthesis of 2-hydroxy-2'-(4-bromobenzyloxy)biphenyl_3_carbonase (63): Paraformaldehyde (〇_98g, 33mmol), Anhydrous magnesium chloride (2.lg, 22 mmol), >^,;^;^',:^'-tetramethylethylidene diamine (butyl ketone) (3.3 mL, 22 mmol) and tetrahydrofuran ( 36 mL) was charged into the reaction vessel, and the temperature was maintained at 65 °C. Starting material (62) (3.2 g, 10 mmol) was added to the mixed solution and washed with tetrahydrofuran (3 · 6 g). After stirring at 70 ° C for 15 hours, the reaction was stopped by adding 2 m ο 1 / L of hydrochloric acid. After the neutralization, the acetonitrile was saturated and the aqueous layer was extracted with ethyl acetate. The organic layer was washed three times with water (1 〇 〇 m L ), and then ethyl acetate was evaporated to give a crude crystal. The crude product was washed with isopropyl alcohol to give a white crystals of hydroxy aryl aldehyde (63) ( 2.64 g ) yield yield of 63.3%, and HPLC relative area percentage of 98.9%. 'H-NMR (3 00MHz, CDC13) <5; 5.01 (s,2H,-0-CH2-), 6.92~7.18(m,5H), 7.27~7.45(m,3H), 7.51~7.61 (m , 3H), 9.95 (s, 1H, -CHO), 11.37 (s , 1 H, -OH ). HPLC analysis conditions: column name Inertsil ODS-3 4.6xl50mmx3// m, solution acetonitrile / 20 mM sodium acetate solution = 96/4 (v/v), flow rate 1.0 m L / min, column temperature 40 ° c, Hold time 2 · 5 minutes, analysis wavelength 254nm. -55-201002659 Example π Synthesis of 2-hydroxy-2'-(2-methoxybenzyloxybiphenyl-3-carbaldehyde (73) is as follows (Reaction formula 14). [Chem. 21] Halogenation Alkyl compound

(Synthesis of hydroxyaryl compounds) Synthesis of 2'-(2-methoxybenzyloxy)-1,1'-biphenyl-2-ol (72): 2,2-bisphenol (3.7 g, 20 mmol) Potassium carbonate (2_8g, 2〇mm〇l) and acetone 24mL were put into the reaction vessel and heated to 6 (TC) with an oil bath under stirring. 2-Methoxybenzyl chloride (71) (3.13g > 20mm〇 l) Into the suspension, stir at 60 ° C for 17 hours. After confirming the reaction conversion rate by Η PLC, the reaction was stopped by adding a saturated aqueous solution of ammonium chloride. After separation, the aqueous layer was extracted with ethyl acetate, and concentrated and concentrated. The crude product was obtained. The crude product was recrystallized from 2-propanol to give a white crystalline hydroxy aryl compound (7 2 ) (5.5 8 g). The yield was 91.0%. 'H-NMR ( 300 MHz » CDC13 δ ; 3.81 ( s,3H,. OCH3-) ' 5.15 ( s ' 2H ' -OCH2- ) , 6.60 ( s - 1H > -〇H ) , 6_82 〜6_93(m,2H) , 6.95 〜7. 〇3(m,2H) ,7_〇5 ～ 7.18 ( m > 2H ) '7.18~7.31(m,4H) ,7.31 to 7.40( m ,2H ). -56- 201002659 (Synthesis of hydroxyaryl aldehyde compounds) Synthesis of 2_hydroxy-2'-(2-methoxybenzyloxy)·ι,ι'-link -3_Carboxaldehyde (73): Paraformaldehyde (〇.9〇g' 30mm〇l), anhydrous magnesium chloride (1.9g, 20 mmol), N,N,N',N'-tetramethylethylidene Diamine (TMEDA) (3.0 mL, 20 mmol) and tetrahydrofuran (31 mL) were placed in a reaction vessel, and the temperature was maintained at 65 ° C. The starting materials (7 2 ) ( 3 · 2 6 g, 1 O.Ommol ) were charged. The mixed solution was washed with tetrahydrofuran (3.1 g). After stirring at 70 ° C for 15 hours, the reaction was stopped by adding 2 mol / L hydrochloric acid. After neutralization, the acetonitrile was distilled off and the aqueous layer was extracted with ethyl acetate. (1 〇〇mL ) After washing the organic layer three times, 'the ethyl acetate was distilled off to obtain a crude product crystal. The crude product was washed with isopropyl alcohol to obtain a white crystalline hydroxyaryl aldehyde (73) ( 2.08 g), the yield was 62.1%, and the HPLC relative area percentage was 99.2%. ^-NMR (300 MHz - CDC13) <5; 3.81 (s > 2H > -〇-CH3) ' 5.12 ( s - 2H,-0-CH2-), 6.74~6.89 (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, lH, - CHO), 11.29 (s, lH, -OH). HPLC analysis conditions: column name Inertsil ODS-3 4·6χ150πΐΓηχ3μ m, dissolving solution acetonitrile / 20mM sodium acetate aqueous solution = 96 / 4 ( v / v ) > flow rate 1.0 mL / min, column temperature 40 ° C, hold time 2.5 minutes , -57- 201002659 Analysis wavelength 254nm. Example 1 2 Synthesis of 2-hydroxy-2'-(2-fluorobenzyloxy)-1,1'-biphenyl-3-carbaldehyde (8 3 ) is as described below (Reaction formula 15). Halogenated alkyl compound

(Synthesis of a hydroxyaryl compound) Synthesis of 2'-(2-fluorobenzyloxy)-1,1biphenyl-2-ol (82): 2,2-bisphenol (24_218, 13〇111111〇1), Potassium carbonate (8.988' 6 5 mmol), hydrazine: potassium (4.32 g, 26 mmol) and acetone 120 g were placed in a reaction vessel and stirred at 20 to 25 °C. After the 2-fluorobenzyl bromide (81) (2 4 · 5 7 g, 1 30 m m ο 1 ) was added to the reaction solution, the reaction was stirred at 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. After the liquid separation, the aqueous layer is extracted with chloroform, and the organic layer is combined, concentrated, and then subjected to silica gel column chromatography (hexane: acetic acid The ester was modified to give a pale brown crystal of the hydroxyaryl compound (82) (26.55 g), and the yield was 69.4%. j-NMR ( 3 00MHz, CDC13 ) ^ ; 5_17 ( s ' 2H ' - OCH2- ) , 6_17(s,lH,-OH) , 6.97~7.20(m,7H) ' -58- 201002659 7_22 ～7_43 ( m , 5H). (Synthesis of a hydroxyaryl aldehyde compound) Synthesis of 2-hydroxy-2'-(2-fluorobenzyloxy)-1,1biphenyl-3-carbaldehyde (83): For a flask equipped with a stirring machine and a reflux tube After nitrogen substitution, the secondary ketone (4.62 g, 154 mmol), anhydrous chlorination table (_l 〇.2 g, 1 07 mmol) was added to start the starting material (82) (15_lg, 51.2 mmol) and acetonitrile (10 mL), 20 Stirring was carried out at 25 °C. N,N,N',N'-tetramethylethylidene diamine (TMEDA) (11.84 g, 102 mmol) was added dropwise to the reaction solution. After the reaction solution was stirred at a reaction temperature of 7 5 to 80 ° C for 16 hours, it was cooled to 15 to 20 ° C and then 2 mol / L of hydrochloric acid was added to stop the reaction. After neutralizing the reaction solution, the acetonitrile was distilled off, and the aqueous layer was extracted with ethyl acetate. The organic layer was combined and evaporated to give a crude product. The crude product was recrystallized from chloroform-hexane-ethyl acetate to give pale-yellow crystals of hydroxy aryl aldehyde (8 3 ) (1 〇 _3 g). The yield was 62.7%. 'H-NMR (3 00MHz > CDCI3 ) δ ; 5.15 ( s, 2Η, -OCH2 ) , 6.95 〜 7_12 (m, 5H) , 7.17~7.41 (m, 4H) , 7.53~7.61 (m, 2H) , 9.94 (s, 1H, .CHO) > 11.32 (s, 1H, -OH ). Example 1 3 Synthesis of 2-hydroxy-2'-(2-phenylbenzyloxy)-1,1'-biphenyl-3-carbaldehyde (93) is as described below (Reaction formula 16). -59- 201002659 [Chemical 23] Halogenated alkyl compound

Magnesium chloride

TMEOA paraformaldehyde acetonitrile (synthetic hydroxy aryl compound) Synthesis of 2'-(2-phenylbenzyloxy)_1,1'-biphenyl-2-ol (92): 2,2-bisphenol (18_628,10) 〇111«1〇1), potassium carbonate (6.91g, 50. Ommol), potassium selected (3_32g, 20.0mmol) and acetone 90g were placed in a reaction vessel and stirred at 20 to 25 °C. 2-Phenylbenzyl bromide (91) (24-71 g, 100 mmol) was placed in the reaction solution, and stirred at a reaction temperature of 5 5 ° C for 27 hours. After cooling to 20 to 25 ° C, the reaction solution was added to a saturated aqueous solution of ammonium chloride to stop the reaction. After the liquid separation, the aqueous layer was extracted with chloroform, and the organic layer was combined, concentrated, and then recrystallized from ethyl acetate-diisopropyl ether-hexane to give a yellow oily hydroxy aryl compound (92) ( 34.38g), the harvest rate was 97.6%. j-NMR (300MHz, CDC13) 3 ; 4_97 ( s ' 2H, - 〇CH2- ) , 6.30 (s, lH'-OH) '6.84 ~ 6.90 (m'lH) ' 6.96 〜7_05 ( m, 2H) , 7_06 ~7·14 (m,1H) ' 7.19 ~ 7.43 ( m,1 3H ). (Synthesis of hydroxyaryl aldehyde compound) Synthesis of 2-carbyl-2,-(2-phenyl-hydroxy)-1,1'-biphenyl-3-carbon vinegar-60-201002659 (93) After replacing the flask with the reflux tube with nitrogen, add paraformaldehyde (4.6 1 g '1 54 mmol), anhydrous magnesium chloride (9 _ 7 3 g, 1 〇 2 mm ο 1 ), and start the starting material (92) (18 g, 51 mmol). Acetonitrile (i44g) was stirred at 20 to 25 tons. Ν,Ν,Ν',Ν'-tetramethylethylidene diamine (TMEDA) (ll_86g' 102mmol) was added dropwise to the reaction solution, and the reaction solution was stirred at 80 ° C for 24 hours. The reaction was stopped by cooling to 20 to 25 ° C and adding 2 mol 1 / L of hydrochloric acid. After neutralizing the reaction solution, it was extracted with chloroform, and the organic solvent was evaporated to give a crude product. The crude product was recrystallized from chloroform-hexane-ethyl acetate to give a white crystal of hydroxy aryl aldehyde (93) (i? g). 'H-NMR (3 00MHz ' CDC13 ) δ ; 4.96 (s> 2H--0 C Η 2 - ) , 6_81 ~ 6.86 (m, lH) , 6.98 ~ 7. 〇 8 (m, 2H) , 7.20 ~ 7_43 (m, 11H), 7.50 to 7.57 (m, 2H), 9.95 (s, lH, -CHO), 11.33 (S, 1H, -OH). Example 1 4 Synthesis of 2-hydroxy-2'-(2,4,6-tri-i-propylbenzyloxy),-biphenyl-3-carbaldehyde (1〇3) as described below (Reaction formula 17) Documented. [Chem. 24]

201002659 (Synthesis of hydroxyaryl compounds) Synthesis of 2,-(2,4,6-tri-i-propylbenzyloxy)biphenyl-2-ol (102): 2,2-bisphenol (7.36§, 39_51^111〇1), potassium carbonate (2.84§, 20.5mmol), cesium iodide (1.32g, 7.95mmol) and acetone 35g were placed in a reaction vessel and stirred at 20 to 25 °C. 2,4,6-Tri-i-propylbenzyl chloride (101) (9.99 g, 39.5 mmol) was placed in the reaction solution, and the reaction was stirred at 55 ° C for 39 hours and then cooled to 20 to 25 °. C, a saturated aqueous solution of ammonium chloride is added to the reaction solution to stop the reaction. After separation, the aqueous layer is extracted with ethyl acetate, and the combined organic layer is dried with magnesium sulfate, and concentrated to give a pale orange-white crystalline hydroxy aryl compound ( 1 0 2 ) (1 3.9 g), the harvest rate was 8 7.2%. 'H-NMR ( 3 00MHz ' CDC13 ) δ ; 1 · 1 0 ( d, J = 6 · 9 Η ζ, 12H) ' 1.24 ( d, J = 6.9 Η ζ > 6 Η ) ' 2.86 ( qq 5 J = 6.9 Η ζ >

1 Η ) ' 3_04 ( qq ' J = 6.9Hz, 2H ) , 5.06 ( s, 2H ) , 6.45 (s, 1H) , 6.87 ~ 7.01 (m, 4H) , 7.14 ~ 7_29 (m, 4H ), 7_34 ~ 7_46 ( m, 2H ). (Synthesis of a hydroxyaryl aldehyde compound) Synthesis of 2-hydroxy-2'-(2,4,6-tri-indolyl-propylbenzyloxy)-1,1'-biphenyl-3-carbaldehyde (103): After nitrogen substitution of the flask equipped with the stirring machine and the reflux tube, paraformaldehyde (3.13 g, 4 mmol), anhydrous magnesium chloride (6.62 g, 69.6 mmol), starting material (102) (14.0 g, 34.8 mmol) and B-62-201002659 A anti-and white is 90 (20 2- 2-化 • nitrile (l〇〇mL), stirred at 20 to 25 ° C. The Ν, Ν, Ν ', Ν '- four base extension B Diamine (TMEDA) (8.08g, 69_6mmol) was dropped into the solution, and the reaction solution was stirred at 80 ° C for 3 hours, then cooled to 20 to 25 ° C and then added with 2 mol / L of hydrochloric acid. The reaction mixture was extracted with dichloromethane, and the organic solvent was evaporated to give a crude product. The crude product was recrystallized from chloroform-hexane-ethyl acetate to give crystals of hydroxy aryl aldehyde compound ( 103) (11.8g), harvest rate 7 8.5%. ^-NMR (3 00MHz > CDC13) <5 ; 1 · 1 0 ( d, J = 6.9 Η z 12H) , 1.22 ( d, J = 6.9Hz , 6H ) , 2.84 ( qq > J-6.9Hz 1 H ) , 3.13 ( Qq, J = 6.9Hz > 2H ) , 4.99 ( s > 2H ) , 6. ~ 6.99 (m, 3H) , 7.04 ~ 7.12 (m, lH) , 7.20 ~ 7.31 m > 2H ) , 7.39~7_49 (m, 3H) , 9.85 (s, lH) » 11. (s, l H ). Industrial Applicability The production method of the present invention can produce a 2-hydroxyaryl aldehyde compound at a high yield while suppressing by-products. Further, the hydroxyaryl aldehyde compound which can be produced by the present invention is suitably used as a material for a photosensitive photoresist composition, a hardener, a color developer or a ligand intermediate of an asymmetric synthesis catalyst. -63-

Claims (1)

201002659 VII. Patent application scope: 1 · One following formula (2 [3] The method for producing a 2-hydroxyaryl aldehyde compound represented by the formula (wherein ri, r2, and R are the same as defined below) is characterized by the presence of the formula (a) [Chemical 9 9 V RIN 9 R— N 9 R (in the formula (a), 'R9 is a Cl-3 group' or two R9 groups on the same nitrogen atom form =CH-R10 'R10 is a C^2 aryl group (the aryl group is Unsubstituted, or substituted by an amine compound represented by a Ci4 alkyl group, a C 1-4 alkoxy group, and a halogen atom selected from the same or different one or more substituents, and η is 0 or 1 to an integer) , make the formula (1) [Chemical 1] R4 Η OH 64 - 201002659 R are each independently a hydrogen atom (in the formula (1), R1, R: are 1 to 3 phenyl groups (the phenyl group is unsubstituted, or ', the substituent A and the hydroxyl group are selected the same or phase a C.·4 alkyl group substituted by one or more substituents of the C, _4 alkyl group and the halogen atom, which are substituted with one or more substituents which are the same or different from each other. a phenyl group substituted with 3 phenyl groups (the side group is unsubstituted or substituted with the same or different substituents selected from the substituent A and the hydroxy group) (the benzene ^ The fluorenyl group is unsubstituted or substituted with the same or different i or more substituents selected from the substituent A and the hydroxy group, and the phenyl sulfonyl group is unsubstituted or Substituent A and the same or different one or more substituents selected from the hydroxyl group) or substituent A, R2 and R3 may form together -Cr5 = cr6_cr7 = cr8_, in which case r5, R6, R7 and R8 are each independently a hydrogen atom or a substituent A, the substituent A is a halogen atom, a d.4 alkyl group, a c,.4 haloalkyl group, a C4 alkoxy group, a Cm octaoxy group, a Cm group Aryl group (the aryloxy group and the aryl group are unsubstituted, or are C.4, Cm-halogen, Cm alkoxy, d.4 alkylcarbenyloxy, Cm aryl (the aromatic The group is unsubstituted or substituted with one or more substituents selected from the same or different ones of the Ci4 alkyl group, the Ci4 halogen compound group and the C^4 alkoxy group), t-butyldimethylmethylalkyl group, c6 22 Arylmethoxy (the arylmethoxy group is unsubstituted or substituted by a heart-4 alkyl group (^-4 alkoxy group, a halogen atom, and the same or different substituents selected from the phenyl group) And a hydroxyaryl compound represented by a substituent selected from the same or different ones of the halogen atoms, or a substituent selected from a nitro group or a cyano group, reacted with anhydrous magnesium chloride and paraformaldehyde to cause The ortho-position of the hydroxyaryl compound is -65-201002659. The method of the invention of claim 1, wherein R1 is a hydrogen atom, a phenyl group (the phenyl group is unsubstituted, or is a Cl_4 alkane). Base, Cl 4 haloalkyl, Ci-4 alkoxy, Cm alkyl carboxyoxy, q ^ aryl (the aryl group is unsubstituted or C?-4 alkyl, Cl "haloalkyl" and Ci_4 Alkoxy The same or different one or more substituents are selected in the group, Cm aryl methoxy (the methoxy group is unsubstituted, or is a C 4 alkyl group, a Ci 4 alkoxy group, a tooth atom, and a benzene group). One or more substituents selected by the same or different substituents in the group) and one or more substituents selected from the same or different halogen atoms in the group are substituted or naphthyl (the naphthyl group is unsubstituted or is a C 4 alkyl group) , Ci_4 haloalkyl, C!-4 alkoxy, Cl_4 alkyl carboxyoxy, aryl (the aryl group is unsubstituted or selected by Cl_4 alkyl, Cl_4 haloalkyl and Ci_4 alkoxy) Substituted or different i or more substituents substituted), butyl butyl dimethyl decyl 'Cm aryl methoxy (the aryl methoxy group is unsubstituted, or is & 4 alkyl, C, _4 alkoxy Substituting one or more substituents of the same or different substituents selected from the group consisting of a halogen atom and a phenyl group) and one or more substituents selected from the same or different halogen atoms, which are optically active or optically inactive, R2 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 pentafluoroethyl group. , R3 and R4 are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a desert atom, a ya atom, a methyl group, an ethyl group, an i. propyl group, a t-butyl group, a trifluoromethyl group, a methoxy group, an ethoxy group. , i-propoxy and (-butoxy). 3. The manufacturing method according to the scope of the patent application, wherein ... is a hydrogen atom, a phenyl group (the phenyl group is unsubstituted, or is Ci 4 alkyl, c: two 1-4 national base - 66- 201002659 , Ci-4 alkoxy, Cw alkylcarbenyloxy, c^2 aryl (the aryl group is oxime, substituted or substituted by C1·4, fluorenyl, Ci-4 haloalkyl and Ch alkoxy One or more substituents selected in the same or different substituents), C 6 2 2 aryl methoxy (M-aryl methoxy group is unsubstituted, or alkyl, cl-4 alkoxy, halogen atom And one or more substituents selected from the same or different substituents in the phenyl group) and one or more substituents selected from the same or different substituents in the tooth atom) or a naphthyl group (the naphthyl group is unsubstituted or c14) Alkyl, c14 haloalkyl, C!-4 alkoxy 'Cl_4 alkyl carboxyoxy, Cm aryl (the aryl group is unsubstituted or C?·4 alkyl, Cl-4 haloalkyl And the same or different one or more substituents selected in the Cl_4 alkoxy group), t-butyldimethylmethylalkyl group, ce_22 aryl methoxy group (the aryl methoxy group is unsubstituted, or Ci.4 hospital base, C^4 alkoxy group, halogen atom and phenyl group Substituting one or more substituents of the same or different substituents and one or more substituents selected from the same or different halogen atoms, which are optically active or optically inactive, and R2 and R3 may form together - cr5 = cr6-cr7 = cr8-, R5 and R7 are each independently 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, Methoxy, ethoxy, i-propoxy or t-butoxy, R6 is a hydrogen atom, a fluorine atom 'a chlorine atom, a bromine atom, an iodine atom 'methyl, ethyl, i-propyl, t- Butyl, trifluoromethyl or pentafluoroethyl, R8 is a hydrogen atom or a fluorine atom. 4. The method of claim 1, wherein R9 is methyl, ethyl or two R9 on the same nitrogen atom together form = CH-R10, R1Q is phenyl, 2-fluorophenyl, 2- Methylphenyl, 2-methoxyphenyl or 2-i-propoxyphenyl. -67- 201002659 IV Designated representative map: (1) The representative representative of the case is: None. (2) Simple description of the symbol of the representative figure: None 201002659 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: none