WO2001014336A1 - Benzene derivatives substituted by aromatic ring and process for producing the same - Google Patents

Abstract

A novel process by which benzene derivatives substituted by an aromatic ring which are represented by general formula (9) are produced in high yield from an inexpensive material under mild reaction conditions. [In the formula, X represents an optionally substituted benzene ring, optionally substituted naphthalene ring, optionally substituted five- or six-membered heterocycle having at least one of nitrogen, oxygen, and sulfur, or optionally substituted condensate of any of these with benzene; Y represents CO2R6, CN, NO2, SO3R6, SO2NR4R5, SO2R6, or SO2R6; and R4, R5, and R6 each represents hydrogen, optionally substituted C1-6 alkyl, phenyl, etc.]

Description

 Description Aromatic ring-substituted benzene derivatives and their production

 The present invention relates to pharmaceutical intermediates, particularly angiotensin II receptor antagonists (210th-ACS National meeting, MEDI 063 and 209th-ACS National Meeting, ORGN 120), factor Xa inhibitors (Annual Report in Medicinal Chemistry, vol. 34, 81, Academic Press). Aromatic ring-substituted benzene derivatives that are very useful as intermediates such as protease inhibitors (J. Med. Chem., (1998), 41, 3378) And its manufacturing method.

 The aromatic-substituted benzene derivative of the present invention is also useful as an intermediate for agricultural chemicals, liquid crystals, heat-resistant polymers, liquid crystalline polymers, and the like.

Background art

Conventionally, as a method for producing a biphenyl derivative, l) a method based on the Ullman reaction (Japanese Patent Application Laid-Open No. 5-257564), 2) an organometallic compound and a halogenated aryl A method of coupling a compound in the presence of a catalyst such as a Pd complex (Japanese Patent Application Laid-Open No. 5-978113, Japanese Patent Application Laid-open No. Hei 6-234690), 3) Nodulation catalyst The catalyst compound with a Ni catalyst and Coupling method in the presence of metal powder (Japanese Patent Application Laid-Open No. 6-61553), 4) Tetra by cyclizing poly-cyanoky cinnamate and butadiene A method for synthesizing a hydroxyphenyl derivative and producing it by dehydrogenation and decarboxylation (Japanese Patent Laid-Open No. 9-87238), 5) Cyclo The cyclohexenol derivative, which is converted from the xenon derivative, is dehydrated and produced by dehydration of the cyclohexagen derivative and the dehydrogenation reaction. Method (Japanese Patent Application No. 11-1497211), 6) Conversion of cyclohexenone derivative to cyclohexahexane derivative, followed by dehydrochlorination. In addition, a method for producing the same (Japanese Patent Application Laid-Open No. 11-49722) is known.

 In addition, as a method for producing a heterocyclic-substituted benzene derivative, an organometallic compound such as boron disulfide and a halogenated aryl compound are reacted in the presence of a catalyst such as a Pd complex. There are known printing methods (Tetrahedron Letters, 36, 5247 (1996), Tetrahedron Letters, 32, 2273 (1991)).

However, conventional methods based on coupling (Japanese Patent Application Laid-Open Nos. 4-2575764, 5-978113, Japanese Patent No. 6-234690, Japanese Patent No. — 6 5 1 5 3, Tetrahedron Letters, 36, 5247 (1996), In Tetrahedron Letters, 32, 2273 (1991)), the production of organometallic compounds under anhydrous conditions, reactions under high-temperature and high-pressure conditions, and expensive catalysts are required. There were many problems in terms of facilities and costs.

 Further, in the production method of Japanese Patent Application Laid-Open No. Hei 9-87272, high-temperature and high-pressure reaction conditions were required. Since the selectivity of the reaction is not necessarily high in these production methods, there are problems such as generation of many by-products and complicated isolation and purification.

Further, the production method of No. 1 1—4 9 7 2 1 has a reaction yield of 4 3 in the dehydration reaction when converting a cyclohexenol derivative to a cyclohexadiene derivative. %, There is a problem in the synthesis yield, etc. In the production method of JP-A-11-49722, chlorine remains in the product in the dehydrochlorination reaction of the cyclocyclohexadiene derivative. Disclosure of invention _c which had problems such as contamination of the obtained chlorobiphenyl derivative

 The present invention provides a novel method for producing an aromatic ring-substituted benzene derivative with high selectivity and high yield under mild reaction conditions using inexpensive raw materials, and aims to solve the above problems.

That is, the present invention [1] General formula (1)

X

 0 '(1)

[Wherein X is at least one of Ν, 0, and S and is a 5- or 6-membered optionally substituted heterocyclic ring or an optionally substituted heterocyclic ring and benzene. Condensate (however, the number of substituents is 1 to 3 and may be the same or different, and may be substituted, Η, 0 置換, or substituted (^ to ( ₆ Optionally substituted C ₂ -C ₆ alkenyl group, optionally substituted C ₂ -C _G alkynyl group optionally substituted Ci-C ₆ alkoxy group, optionally substituted alkylthio group , NR ⁴ R ⁵ , NO LOGOGEN, NO CN, COR

C0 ₂ R ⁶ , C0NR ⁴ R ⁵ , S0 ₃ R ⁶ , S0 ₂ NR ⁴ R ⁵ , S0R ⁶ , S0 ₂ R ⁶ , 0C0R ⁶ , 0C0 ₂ R ⁶ , 0C0NR ⁴ R ^{5 0} S0 ₂ R ⁶ , replaced A phenyl group which may be substituted, a phenyl group which may be substituted, a heteroaryl group which may be substituted or a heteroaryl group which may be substituted. , shows a good) be formed 4-7 membered ring I by the substituents meet Ri next to the al, Y is ^{_{C0 2 R 6, CN, NO}} 2, S0 3 R 6, S0 2 NR 4 R ⁵ , SOR ⁶ , S 0 ₂ R ⁶ , R ⁴ , R ⁵ and R ⁶ are H, substituted or unsubstituted (^ to ( ₆ alkyl groups or substituted substituted) R ⁴ and R ⁵ may form a 4- to 7-membered ring. And a general formula (2)

[Wherein II ¹ , R ¹ and R ³ are H, optionally substituted (^ to ( ₆ alkyl groups, optionally substituted C _{2 to} C ₆ alkenyl groups, and optionally substituted Good C ₂ -C ₆ alkynyl group, optionally substituted (^-(] ₆ alkoxy group, optionally substituted alkylthio group, NR ⁴ R ⁵ , NO ₂ O gen, N 0 ₂ , CN , COR ⁶ , C0 ₂ R ⁶ , C0NR ⁴ R ⁵ ,

^{_{S0 3 R 6, S0 2 NR}} 4 R 5 s S0R 6, S0 2 R 6, OCOR 6, 0C0 2 R 6, OCONR 4 R 5, 0S0 2 R 6, optionally substituted phenylpropyl group, substituted R represents an optionally substituted phenyl group, an optionally substituted heteroaryl group or an optionally substituted heteroaryl group;

R ⁵ and R ⁶ is described. ] To react with the general formula (4)

[Wherein X, Y, R ¹ , a ′ and R ³ represent the above. A general formula characterized by synthesizing a compound represented by the formula ( Five )

[Wherein X, Y, R ¹ , R ′ and R ³ represent the above. A method for producing a xenopene derivative represented by

 [2] General formula (1)

X

 0 '(1)

[Where X and Υ are the same as those defined in [1]. Ding and general formula (3)

[In the formula, R ¹ and R ³ represent the same as defined in [1], and Z represents a leaving group. ] To react with the general formula (4)

[Where X, Y, R ¹ , R ′ and are the same as those defined in [1]. Show things. Wherein the compound represented by the general formula ( ⁵⁾ is synthesized and then subjected to a cyclization reaction.

Expression _{χ, γ, R i, R} : and ^ have the same meanings as those defined in [1]. A process for producing cyclohexenone derivatives represented by

[3] — General formula (5)

[Wherein X, Y, R ¹ , and R ³ are the same as defined in [ ¹ ]. Is reduced to the cyclohexenone derivative represented by the general formula (6)

[Formulas γ RI, R ^{! And} R ³ are the same as those defined in [1]. Show things. To obtain a cyclohexenol derivative represented by the general formula:

(7)

[Wherein X, Y, R and R ³ represents a the ones same also to that defined in [1], Q is a halogen, a _{^{0C0R 7, 0C0 2 R 7,}} OCONR 4 R 5 or 0s0 ₂ R ⁷ And R ⁷ may be substituted (^-( _{6 represents} an alkyl group or a phenyl group which may be substituted), and R ⁴ and R ⁵ are those defined in [1]. After conversion to a cyclohexene derivative represented by the general formula (1), an elimination reaction is carried out in the presence of a base to obtain a compound represented by the general formula

(8)

[Where X, Y, R ¹ , R ² and R ³ are the same as defined in [1]. A cyclohexadiene derivative represented by the formula In addition, a general formula (9) characterized by performing a dehydrogenation reaction

[Where X, Y, R ¹ , R ′ and R ^s are the same as defined in [1]. A method for producing a heterocyclic-substituted benzene derivative represented by the formula:

[4] General formula (6)

(6)

[Wherein X is an optionally substituted benzene, naphthylene ring, N,

A 5- or 6-membered optionally substituted heterocycle or a substituted or unsubstituted condensate thereof with benzene having at least one of 0 and S 1 to 3 substituents, which may be the same or different, may be H, 0H, or may be substituted (^ to ( ₆ alkyl groups, optionally substituted C ₂ C ₆ -C ₆ alkenyl group, substituted or unsubstituted C ₂ -C ₆ alkynyl group, substituted or unsubstituted (^-(^ alkoxy group, substituted or unsubstituted alkyl Chiomoto, NR ⁴ R ^S, Nono ^{_{androgenic, N0 2, CN, C0R 6}} , C0 2 R 6, C0NR 4 R 5, S0 3 R 6, S0 2 NR 4 R 5, S0R 6, S0 2 R 6, 0C0R ⁶ , 0C0 ₂ R ⁶ , 0C0NR ⁴ R ⁵ _s 0 _S 0 ₂ R ⁶ , an optionally substituted phenyl group, an optionally substituted phenoxy group, an optionally substituted heteroaryl group or A heteroaryl group which may be substituted, and a 4- to 7-membered ring may be formed by an adjacent substituent), and Y, R ¹ , and R ³ represent Indicates the same as defined in [1]. A cyclohexanol derivative represented by the general formula (7) is obtained by introducing a leaving group in the presence or absence of a base.

[Wherein X, Y, R ¹ , and R ³ represent the above, and Q represents the same as defined in [3]. Is converted to a cyclohexene derivative represented by the formula

(8)

(8) [Wherein X, Y, R ¹ , ^ and R ³ represent the above. A general formula (9) characterized in that after synthesizing a cyclohexadiene derivative represented by the formula:

[Wherein X, Y, R ¹ , ^ and R ³ represent the above. For producing aromatic ring-substituted benzene derivatives represented by the formula:

C 5] General formula (5)

[Wherein X, Y, R ¹ , and R ³ are the same as those defined in [1]. Is reduced to the cyclohexenone derivative represented by the general formula (6)

[Where X, Y, R ¹ , R ² and R ³ are the same as defined in [1]. Show things. The cyclohexenol derivative represented by the general formula (10) is synthesized by performing a dehydration reaction.

[Where X, Y, R ¹ , R ′ and R ³ are the same as defined in [1]. After conversion to a cyclohexadiene derivative represented by the general formula (9):

[Wherein X, Y, R ¹ , R ′ and R ³ represent the same as defined in [1]. A method for producing a heterocyclic-substituted benzene derivative represented by the formula:

[6] General formula (5)

[Where X, Y, R ¹ , and R ³ are the same as defined in [1]. Show things. Is reacted with a halogenating agent to produce a compound represented by the general formula (11A) and / or (11B).

[In the formula, X, Y, R ¹ , R ′ and R ³ represent the same as defined in [1], and W represents halogen. Wherein a halogen derivative represented by the general formula (9) is synthesized, and further subjected to a dehydrohalogenation reaction.

[Where X, Y, R ¹ , R ² and R ³ are the same as defined in [1]. A method for producing a heterocyclic-substituted benzene derivative represented by the formula:

[7] General formula (5)

(Five) [Where X, Y, R ¹ and R ³ are the same as defined in [1]. Is reacted with a nitrogenating agent to form a compound represented by the general formula (11A) and / or (11B)

[In the formula, X, Y, R ¹ , and R ³ represent the same as defined in [1], and represent the same as defined in [6]. By synthesizing a halogen derivative represented by the general formula (12)

[Wherein X, Y, R ¹ , and R ³ represent the same as defined in [1], and W represents the above. Wherein the heterocyclic-substituted halobenzene derivative represented by the general formula (9) is further subjected to a dehalogenation reaction.

(9) [Wherein X, Y, R ¹ , ^ and R ³ are the same as defined in [1]. A method for producing a heterocyclic-substituted benzene derivative represented by the formula:

[8] — General formula (11A) and / or (11B)

[Wherein ^{X, Y, W, R 1} , Ri and R ³ indicates those same as those defined in [4], W denotes those same as those defined in [6]. ] To the halogen derivative represented by the general formula (12)

[Wherein X, Y, W, R ¹ , R ² and R ³ represent the above. A heterocyclic-substituted halobenzene derivative represented by the following general formula (9):

(9) [Where X, Y, R ¹ , Ri and R ³ are the same as defined in [4]. A method for producing an aromatic ring-substituted benzene derivative represented by the formula:

[9] General formula (5)

(Wherein X, Y, R ¹ , R ′ and R ³ are the same as defined in [1].), A cyclohexenone derivative represented by the formula:

[10] — General formula (6)

(Wherein X, Y, R ¹ , R ^; and R ³ are the same as defined in [1].)

[11] General formula (7)

(7) Table in (wherein X, Y, R ^ and R ³ indicates the even Noto same also to define the [4], Q denotes were ones same also to that defined in [3].) Cyclohexenone derivatives

[1 2] General formula (8)

(Wherein X, Y, R ¹ R ′ and R ³ are the same as those defined in [4].)

[1 3] — General formula (10)

(Wherein X, Y, R ¹ , R ^2, and R ³ are the same as defined in [1].)

[14] General formula (11A) and / or (11B)

(11 Α) (1 IB) (Wherein ^{X, Y, R 1, R} 1 and R ³ indicates those defined also the same for the [1], W denotes those defined same also to that in [6].) Noxyloxyhexadiene derivative represented by

[15] General formula (9)

(Wherein X, Y, R ¹ , Ri and R ³ are the same as those defined in [4].)

[16] General formula (1 2)

(Where X, Y, R ¹ , and R ³ represent the same as defined in [4], and W represents the same as defined in claim 6). Aromatic halobenzene derivatives

BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the present invention will be described in detail.

In the general formulas (5) to (12) of the present invention, X is, for example, Optionally substituted benzenes, optionally substituted naphthenes, optionally substituted phenols, optionally substituted francs, Optionally substituted thiophene, optionally substituted pyrazole, optionally substituted imidazole, optionally substituted Isothiazoles, optionally substituted imidazoles, optionally substituted oxazoles, optionally substituted thiazoles, substituted Good pyridin, optionally substituted pyridazine, optionally substituted pyrimidine, optionally substituted virgin, substituted May be done

ル, optionally substituted benzo [b] franc, optionally substituted benzo [b] thiophene, optionally substituted benzo [b] d] imidazole, optionally substituted benzene [d] oxazole, optionally substituted benzo [d] thiazole, optionally substituted Purine, optionally substituted quinoline, optionally substituted isoquinoline, optionally substituted cyanoline, substituted Or substituted oxazolines, optionally substituted quinoxalines, or optionally substituted pteridines, etc. And, preferably, benzene, which may be replaced, naphthene, which Optionally substituted pyrrole, optionally substituted phenyl, optionally substituted thiophene, optionally substituted levirazole, substituted May be substituted isoxazole, may be substituted isothiazole, may be substituted pyridin, may be substituted Redidins, optionally substituted pyrimidines, optionally substituted virazines, optionally substituted installers, optionally substituted Good benzofuran, benzothiophene that may be replaced, quinoline that may be replaced, isoquinolene that may be replaced And, more preferably, optionally substituted benzene, optionally substituted Naphthalene, optionally substituted pyrrole, optionally substituted flaun, optionally substituted tifophane, optionally substituted A pyrimidine, a pyrimidine which may be substituted, may be substituted and a pycnid.

The substituent may be, for example, substituted (^ to (^ is an alkyl group such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group) , Tret-butyl, pentyl, hexyl, trifluoromethyl, chloromethyl, bromomethyl, benzyl, etc .; may be substituted C ₂ to C ₆ alkenyl groups and Such as vinyl group, aryl group, isopropenyl group, butenyl group, pentenyl group, hexenyl group and styrene group; which may be substituted C ₂ -C ₆ Alkynyl groups such as ethynyl group, vinyl group, petenyl group and pentynyl group; may be substituted (the alkynyl group of ^ to ₆ may be substituted; Methoxy, ethoxy, epoxy, isopropoxy, butoxy, tret-butoxy, trifluoromethoxy, benzyloxy NR ⁴ R ⁵ is amino group, methylamino group, dimethylamino group Group, ethylamino group, getylamino group, propylamino group, isopropylamino group, butylamino group, tret-butylamino group, pentylamino group, hexylamino group Mino group, pyrrolidino group, piperidino group, morpholino group, anilino group, etc .; Examples of nitrogen include fluorine, chlorine, bromine and iodine. etc.; N0 _2, CN, COR ⁶ and to the formate group, § Se ethyl group, pro pin Oniru group, Petit Li group, Lee Seo Petit Li group, Bruno, 'Les Li group, Pi Bruno , Oryl, benzoyl, toluyl, furanoyl, nicotinol, isonicotinoyl, cinnamoyl, etc .; C0 ₂ R ⁶ Examples include methoxy-, ethoxy-, propoxy-, butoxy-, tert-butoxy-, benzyloxy-, phenoxy- etc. force reportage sulfonyl group; C0NR ⁴ is a R ⁵ main Chirua Mi Bruno Karuponiru group, di main Chirua Mi Bruno Ca carbonyl group, Echirua Mi Roh Karuponiru group, Jefferies Chirua Mi Bruno Karuponiru group, peak b Li di Bruno carbonyl group, Pipechi di Bruno Ca carbonyl group, Moruho Li Roh mosquito Ruponiru group, § etc. two re Roh force Lupo two Le group; S0 ₃ is a R ⁶ main preparative Kishisurufu O group, e preparative key sheet sulphates O S0 ₂ N, such as a phenyl group, a propoxylithyl phenyl group, a butoxysulfonyl group, a benzyloxysulfonyl group, a phenoxysulfonyl group; R ⁴ R ⁵ is a sulfamoyl group, a methylsulfamoyl group, a dimethylsyllefamoyl group, a ethylsulfamoyl group, a getylsulfamoyl group, Propyl sulfamyl group, isopropyl pyrrhamyl group, butyl sulfamyl group, tret-butylsulfamyl group, pentylsulfamyl group Lille group, pyrrolidinosulfamyl group, piberizinosulfamyl group, morpholinosulfamyl group, anilinosulfamoy group S0R ⁶ includes methylsulfinyl, ethylsulfinyl, propylsulfur, petite Luz Le full I group, Ben Jirusurire full I group, full et Nils Le full I sulfonyl group, etc.; S0 ₂ is an R ⁶ main Chiriresuru off O group, Echiru sulphates O group, Pro Wills Le A phenyl group, a butylsulfonyl group, a benzylylsulfonyl group, a phenylsulfonyl group;

0C0R ⁶ includes acetyloxy, propionyloxy, butyryloxy, isobutylyloxy, no, “relyloxy, pinoyloxy” and benzoyloxy. Lee Rireoki sheet group, preparative Ruoi Ruoki shea group, off La Roh Lee Rireoki shea group, Nico Chi Roh i Ruokishi group, Lee Seo two co Chi Roh i Ruoki shea group, etc. shea N'namo Lee Ruokishi group; 0C0 and ₂ R ⁶ Methoxycarbonyl, ethoxycarbonyl, carbonyloxy, propoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl and benzyloxycarbonyl And OCONR ⁴ R ^{5 such} as methylaminocarbonyloxy group, dimethylaminocarbonyl group, and phenyloxycarbonyloxy group. Ethylamino propylonyloxy group, getylamino carbonyloxy group, pyrrolidino carbonyloxy group, bipetidino carbonyloxy group, morpholino carbonyloxy group, anilino carbonyloxy group Do etc.; 0S0 ₂ R ⁶ and to the main evening down scan le off O Niruo key sheet group, E evening main routine off O Niruokishi group, pro pan scan Levonyloxy group, Butanesulfonyloxy group, Pentansulfonyloxy group, Hexanesulfonyloxy group, Benzensulfonyloxy group, Toluenesulfone A phenyl group which may be substituted, such as a hydroxyphenyl group, a chlorophenyl group, a methylphenyl group, and a triphenyl group; Fluoromethyl phenyl, methoxyphenyl, tret-butoxyphenyl, benzyloxyphenyl, trifluoromethoxyphenyl Phenyl, phenyl, etc .; phenyl, hydroxy, phenyl, etc., even if they are substituted, Rolophenoxy, methylphenoxy, trifluoro Substituents such as methylenoxy group, methoxyphenoxy group, trifluorooxyenoxy group, phenoxyenoxy group, etc .; substitution Heteroaryl groups that may be used include phenyl, phenyl, thienyl, azolyl, pyridyl, and indril groups; Examples of the heteroaryl group include a phenyloxy group, a phenyloxy group, an azo'lyloxy group, a pyridyloxy group, and an indyloxy group. Is

Preferred and rather is H, optionally substituted (^ - ₍₆ alkyl group, but it may also be substituted (^ - ₍₆ Arco key sheet group, Nono b gain down, NO ₂ NR ⁴ R ^5, substituted optionally Yo Rere full et alkylsulfonyl group which may, optionally substituted off even if We Roh key sheet ^{_{group, C0R 6, C0 2 R 6}} , 0C0R 6, 0C0 2 R 6 der Ri, rather then preferred especially is H, methylation group, main preparative key sheet group, full et Bruno alkoxy group, main preparative Kishika Rubo group, e preparative key deer Ruponiru group, N0 _2, § Seto alkoxy group or It is a benzoyloxy group.

 The ring formed by adjacent substituents as the substituent for X includes a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, and a cyclohexane ring. Examples include a chlorobutane ring, an oxetane ring, a tetrahydrofuran ring, a fran ring, a pyran ring, a dioxolan ring, and a dioxane ring.

Examples of Y include, for example, CO ₂ R ⁶ such as a methoxycarbonyl group, a ethoxycarbonyl group, a propoxycarbonyl group, a butoxycarbonyl group, a tert-butoxycarbonyl group, and a benzyloxy group. etc. Karupo a group, CN, N0 _2, SO ₃ is in the R ⁶ main preparative Kishisuru off O sulfonyl group E preparative key cis Le off O group, pro epoxy sulphates O group, blanking preparative key Thistle off O SO ₂ NR ⁴ R ⁵ , sulfyl group, methylsulfamine group, dimethylsulfonyl group, benzyloxysulfonyl group, phenoxysulfonyl group, etc. Moyl group, ethyl sulfamyl group, getylsulfamylyl group, propylsul Famyl group, isopropyl sulfamyl group, butylsulfamyl group, tret-butylsulfamyl group, pentylsulfamyl group, hexylsulfur Famyl group, pyrrolidinosulfamyl group, piberidinosulfamyl group, morpholinosulfamyl group, anilinosulfamyl group S0R ⁶ includes methylsulfinyl phenyl, ethylsulfinyl, propylsulfinyl, butylsulfinyl, benzylsulfinyl, benzylsulfinyl, etc. d Niels Ruff I group, S0 ₂ R ⁶ and to the main Chirusu Le off O group, Echirusurufu O group, pro Birusuru off O group, butyl Surire off O group, base down Jirusu Le off O Nyl group, phenylsulfonyl And the like. In a preferred and rather ^{_{CN, C0 2 R 6, NO}} 2, S0 3 R 6, S 0 2 NR 4 R 5 der is, particularly preferred and rather is CN, main preparative alkoxycarbonyl group, E preparative key deer Ruponiru group is there .

Is the Z rather than by if a substituent that having a function of the leaving group, eg if Ha Russia Xuan and is in full Tsu iodine, chlorine, bromine, iodine, in the 0C0R ⁷ , Acetyloxy group, propionyloxy group, petityloxy group, isopetityloxy group, norreloxy group, pino, 'royoxy group, benzoyloxy group, Toluooxy group, furanoxy group, nicotinoxy group, isonicotinoki group Shi group, etc. Thin Namoi Ruoki shea group, 0C0 ₂ is a R ⁷ main preparative key imposes Ruponiruo alkoxy group, e preparative carboxymethyl Karuponiruo key sheet group, pro epoxy Karuponiruokishi group, blanking preparative carboxymethyl Cal Poni Ruo alkoxy group, tert- Bed DOO alkoxy Karuponiruokishi group, benzyl O carboxymethyl Cal Poni Ruo key sheet group, etc. full et Bruno Kishika Ruboniruokishi group, 0C0NR ⁴ R ⁵ and to the methylation a Mi Roh Karuponiruo alkoxy group, dimethyl Chirua Mi Bruno mosquito Ruponiruokishi Group, ethylaminocarbonyl group, ethylaminocarbonyl group, pyrrolidinocarbonyl group, piperidinocarbonyl group, morpholinocarbonyloxy group, anilininocarponyloxy group, etc. , 0s0 ₂ R ⁷ and to the main evening Nsu Le off O sulfonyl Okishi group, ethacrylic emission scan le off O Niruoki Shi , Propane sulfonyloxy group, butanesulfonyloxy group, pentanesulfonyloxy group, hexansulfonyloxy group, trifluorene sulfone Phenyloxy group, benzenesulfonyloxy group, acetyloxy group, toluenesulfonyloxy group, and the like, preferably chlorine, bromine, iodine, acetyloxy group, benzene, etc. Zyloxy, methoxycarpoxy, ethoxycarpoxy, tert-butoxycarpoxy, dimethylaminocarboxy, methanesulfonoxy , Particularly preferred are a sulfonyloxy group, a trifluoromethanesulfonyloxy group, a benzenesulfonyloxy group, and a toluenesulfonyloxy group. And a chlorine, bromine, acetyloxy group, methoxycarbonyl group, methansulfonyloxy group, or toluenesulfonyloxy group.

 Examples of W include fluorine, chlorine, bromine and iodine, preferably chlorine and bromine, and particularly preferably chlorine.

R ¹ and R ³ are, for example, H; and optionally substituted C 丄 to C ₆ alkyl groups are a methyl group, an ethyl group, a propyl group, and an isopropyl group. , Butyl, tret-butyl, pentyl, hexyl, trifluoromethyl, chloromethyl, bromomethyl, benzyl, etc .; The C _{2 to} C ₆ alkenyl groups may be vinyl, aryl, isopropenyl, butenyl, pentenyl, hexenyl, and styrene. A C ₂ -C ₆ alkynyl group which may be substituted, such as an ethynyl group, a propynyl group, a petynyl group, a pentynyl group; and the like. (^ ~ (^ Are methoxy, ethoxy, propoxy, isopro Alkoxy group, blanking preparative alkoxy group, t re t - Bed DOO key sheet group, Application Benefits off Ruo b menu preparative alkoxy group, etc. base down Jiruokishi group; location Examples of the alkylthio group which may be substituted include a methylthio group, an ethylthio group, a propylthio group, a butylthio group, a benzylthio group, a hexylthio group and a benzylthio group; and NR ⁴ R ⁵ and the like. Amino group, methylamino group, dimethylamino group, ethylamino group, ethylamino group, propylamino group, isopropylamino amino group, butylamino group , Tret-butylamino, pentylamino, hexylamino, pyrrolidino, biperidino, morpholino, anilinino, etc .; off is a gain down Tsu-containing, chlorine, bromine, Yo U disjoint etc.; NO _2, CN, formate Le group as a COR ^6, § Se ethyl group, flop port Pioniru group, Petit Li Le group , Isobutylyl group, norylyl group, pinoylyl Group, benzoyl group, toluene group, furanoyl group, nicotinylyl group, isonicotinol group, cinnamoyl group, etc .; CO ₂ R ⁶ These include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, tert-butoxycarponyl, benzyloxycarreponyl, and pheno. Xylation Ruponyl group, etc .; CONR ⁴ R ⁵ includes methylaminocarbonyl, dimethylaminocarbonyl, ethylaminocarbonyl, diethylaminocarbonyl, pyrrolidine Nocalponyl, pipetidinocarbonyl, morpholinocarbonyl, aniline Etc. sulfonyl group; S0 ₃ is a R ⁶ main preparative key Thistle off O group, E preparative key Thistle off O group, propoxide cis Le off O group, blanking preparative key cis Le off O group, base down Jiruo key Thistle off O group, full et Roh key cis Le off O alkenyl etc. groups; S0 ₂ NR ⁴ is an R ⁵ Sulf § moi group, methylation sulphates § Mo Lee group, dimethyl Tilesulfamoyl, ethylsulfamoyl, getylsulfamoyl, propylsulfamoyl, isopropylsulfamoyl, butylsulfamoyl Yl group, tret-butylilesulfamoyl group, pentylsulfamyl group, hexylsulfamoyl group, pyrrolidinosulfamoyl group, biperidinosulfamoyl group Group, molyreholinosulfamoyl group, D Re Roh Sulf § Mo Lee le group, etc.; S0R ⁶ and to the main Chirusu relay off I group, Echirusuru full I group, pro Pirusuru full I group, blanking Chirusu Ruff I group, base down Jirusu Le off I group, etc. full Enirusu Le full I sulfonyl group; S0 ₂ R ⁶ a with main Chirusuru off O group, E Ji Luz Le off O group, pro Pils Le off O group, Puchirusu Le off O group, base down Jirusu Ruch O group, etc. off Enirusuru off Oniru group; is a 0C0R ^6, § Se Chiruoki shea group, pro Pioniruokishi group Petit Li Ruokishi group, Lee Seo Petit Li Ruokishi group, Nono ' Reloxy group, pino'-yloxy group, benzoyloxy group, troyloxy group Group, off La Roh I Ruoki shea group, two co Chi Roh Lee Rireo key sheet group, Lee Seo Nico Chi Roh I Ruokishi group, shea N'namo Lee etc. Ruokishi group; 0C0 ₂ is a R ⁶ main preparative key deer Ruponiruoki Group, ethoxycarbonyl group, propoxy carboxy group, butoxy carboxy group, tert-butoxy carboxy group, benzyloxy carbonyl group, genoxy etc. carbonyl O dimethylvinylsiloxy groups; 0C0NR ⁴ R ⁵ and to the main Chirua Mi Roh Karuboniruoki shea group, dimethyl Chirua Mi Roh mosquito Lupo two Ruoki shea group, Echirua Mi Roh mosquito Ruponiruoki shea group, Jechirua Mi Roh mosquito Ruboniruokishi group, Pi L-dinocarbonyloxy group, pitidinocarbonyloxy group, morpholinocarbonyloxy group, anilinocarbonyloxy group Do etc.; 0S0 ₂ R ⁶ and to the main evening Nsu Le off O Niruo key sheet group, ethacrylic emissions sulphates O Niruo alkoxy group, pro Pas Nsu Le off O Niruokishi group, pig down Surire off O Niruokishi group, Pen Tansulfonyloxy group, hexanesulfonyloxy group, benzenesulfonyloxy group, toluenesulfonyloxy group, etc .; Examples of the phenyl group include a hydroxyphenyl group, a black phenyl group, a methylphenyl group, a trifluoromethylphenyl group, and a methoxyphenyl group. Benzyl group, tret-butoxyphenyl group, benzyloxyphenyl group, trifluoromethyxifene group A phenyl group, a phenyloxy group, etc .; substituted or unsubstituted phenoxy groups; Group, chlorophenoxy group, methylenoxy group, trifluoromethylenoxy group, methoxyphenoxy group, trifluorone Methoxy phenoxy group, phenoxy phenoxy group, etc .; a substituted or unsubstituted heteroaryl group may be a phenyl group; Chenyl group, azolyl group, pyridyl group, indolyl group; etc .; Group, azolyloxy group, pyridyloxy group, indyloxy group, etc., preferably H, methyl, etc. Group, ethyl group, propyl group, isopropyl group, butyl group, tret-butyl group, pentyl group, hexyl group, trifluoromethyl group, black methyl group, bromide Even if it is substituted with a methyl group, a benzyl group, etc., (^ ~ (^ alkyl group, hydroxyphenylyl group, cyclophenyl group, methylphenyl group, methylphenyl group) Group, trifluorenemethylphenylene group, methoxyphenyl group, tret-butoxyphenyl group, benzyloxyphenyl group, trifluorenemethyl group An optionally substituted phenyl group such as a xyphenyl group, a phenyloxyphenyl group, particularly preferably H, a methyl group, a methyl group, a propyl group or an iso group Building group, Trifluoromethyl group, chloromethyl group, bromomethyl group, hydroxyphenyl group, chlorophenyl group, methylphenyl group, triphenyl A fluoromethyl phenyl group, a methoxyphenyl group, and a trifluoromethoxyphenyl group.

R ⁴ , R ⁵ and R ⁶ are, for example, H; optionally substituted alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, tret -Butyl, pentyl, hexyl, etc .; phenyl groups which may be substituted and which may be substituted include hydroxyphenyl and cyclophenyl groups. , Methyl phenyl group, trifluoromethyl phenyl group, methoxy phenyl group, trifluoro methoxy phenyl group, phenoxy phenyl group And NR ⁴ R ⁵ include pyrrolidinyl group, biperazinyl group, morpholinyl group, and the like, and preferably, H, methyl group, ethyl group, and propyl group. Pill, isopropyl, pyrrolidinyl, biperazino or morpholino Good or was rather the of et al H, methylation group, Echiru group, Ru pin opening Li di Bruno Motodea.

A preferred compound of the general formula (5) is, for example, 2- (4-pyridyl) -141-year-old oxocyclohexyl 2-ethylencarboxylate , 2-(3-pyridyl) 1 4- 2-ethylene carbonate, 2— (2-pyridyl) -14-oxocyclohexyl 1-2—ethyl carbonate, 2— (2— 2-tro-5-pyridyl) 1 4—Oxocyclohexyl 2—enethyl carboxylate ester, 2— (2—clo 1—5—pyridyl) 1 4-oxocyclohexyl 2—ethyl carboxylester, 2— (2—methoxy-15—pyridyl) 1-4—hydroxycyclohexyl Sea 2—Ethyl ester, 2— (5—Pyrimidinyl) _4 1-year-old oxocyclohexyl 2—Ethyl ester, 2— (2—2 Tro 5-pyrimidinyl) 1 4-Oxocyclohexyl 2-Echinylester 2- (2-chloro-5-pyrimidinyl) 1-4-oxocyclohexyl 2-enethyl ester. 2 — (2—methoxy 5-pyrimidinyl) 1-4-oxocyclohexyl 2-enethyl carboxylate, 2-(4-pyridyl)-1-4-oxocyclohexyl 2-Encarbononitrile, 2-(3-Pyridyl) 14 1 year old Kisocyclohexyl 2-Encarbonitril, 2-(2-Pyridyl ) 14-year-old KIKOSHIKOHRO 2—EN CARBON TRIL, 2— (2—2-TRO 5—PYRIZIL) Kishi 1 2 — Encapsitol, 2 1 (2 — black mouth 5 — pyridyl) 1 4 — oxocyclohexyl 2 — encarponitrile, 2 — (2 — methoxy 5 — pyridyl) 1-4 4-Hydroxycyclohexyl 2—ene carbonitrile, 2- (5—pyrimidinyl) 1-4—oxocyclohexyl 2— Carbonitril, 2 — (2—Nitro-5—Pyrimidinyl) 14 1-year-old Kisocyclohexyl 1 2—Encarbonitril, 2— (2-chloro 5-pyrimidinyl) 1-4-oxocyclohexyl 2-encarboxyl, 2-(2-methoxy 5-pyrimidin) Jinyl) 1 4 — Oxocyclohexyl 2 — Encarbonitrile, 2-(4 — Pyrylyl) 1 4 — Oxocyclohexyl 1 2 — Ensulfone Acid Chilester, 2 — (3 — pyridyl) 14 1 year old Kisocyclohexyl 2 — Enthyl sulfonate, 2 — (2 — pyridyl) 1 4 — Oki Sociocyclohexyl 2—Ethrylefonic acid ester, 2— (2—Nitro-5—Pyridyl) 1-4 4-oxo Ethyl ester sulfonate, 2_ (2—chloro-5—pyridyl) 14 1-year-old chlorocyclohexyl 2—Ethyl sulfonate ester, 2— (2—methyl Toxic-5-pyridyl) —4 year old oxocyclohexyl 2—ethyl sulphonate, 2— (2—amino-5—pyrimidinyl) One 4-oxo Mouth hex 1—Ethyl sulfonic acid ester, 2— (2—Nitro 5—Pyrimidinyl) 14 1-year-old oxocyclohexy 2—Ensulfone Ethyl ester, 2- (2-black mouth 1-5-pyrimidinyl) 14-year-old oxocyclohexyl 2 _ ethyl sulfonate ester, 2 — (2 — Methoxy-5—pyrimidinyl) -4 oxocyclohexyl 2—ethyl sulphonate.

Preferred compounds of the general formula (6) include 4-hydroxy-2 -phenylcyclohexyl 1 -2-ethyl carboxylate and 4-hydroxy. 1-2-(4-methylphenyl) cyclohexyl 2-enethyl carboxylate, 4-hydroxy 2--(4-12 trophenyl) cyclo Hexoxy 2 — ethyl carponic acid ester, 4-hydroxyl 2 — (4 — methoxyphenyl) cyclohexyl 1-2 — encarponic acid ethyl ester Ter, 4-hydroxy 1-2-(41-mouth) cyclohexyl 2-enethyl ester, 4-hydroxy-2-( 4 Bromophenyl) Cyclohexyl 2—Ethylene carbonate, 4—Hydro Roxy 2 — (4-hydroxyphenyl) cyclohexyl 2 — enethyl ester, 4-hydroxy Coxy 2 — phenylcyclohexyl 2 — methyl acetyl ester, 4 — hydroxy 2 — (4 — methyl phenyl) Sea 2—Methyl carboxylate, 4-Hydroxy 2— (4—Nitrophenyl) Cyclohexyl 1—2—Hen carboxylate Chilester, 4 — v — 2 — (4 — methoxyphenyl) cyclohexyl 2 — methyl carboxylate, 4-hide mouth 2 — ( 4 1-mouth phenyl) cyclohexyl 2—methyl carboxylate, 4—hydroxy 2— (4—promophenyl) cyclo Xy 2—Methyl ester carbonate, 4—Hydroxy 1 2— (4-Hydroxyphenyl) to cyclo Ci-2—Methyl encarponic acid ester, 4-Hydroxy —2—Phenylcyclohexyl 2—Henka Reponitrile, 4-Hydroxy1-2— (4-methylphenyl) cyclohexyl 2-encarboxyl, 4-hydroxy 2-(4-diphenyl) cyclo XII 2 — Encapsulated Rep., 4-Hydroxy 2 — (4 — Methoxy Phenol) Cyclohex 2 — Enced. Rep. 2 4-Hydroxy 1 2 — (4 — Black mouth phenyl) Cyclohex 1 2 — Encarponitrile, 4-Hydroxy 1 2 — ( 4 Bromophenyl) cyclohexyl 2 — enecarbonite Lily, 4-hydroxyl 2 — (4-hydroxyphenyl) sic Mouth hex 1 — ene carboditrilyl, 4 — hydroxyl 2 — Phenylcyclohexyl-2—ethyl sulfonate, 4-hydroxy1-2— (4—methylphenyl) cyclohexyl-2-enesulfone Ethyl ester, 4—Hydroxy 1 2 — (4—Nitrophenyl) cyclohexyl 2 — Enethyl sulfonate, 4—Hydroxy 1 2 — (4-methoxyphenyl) cyclohexyl 2—ethyl sulphonate ester, 4—hydroxy 1 2— (41-closed phenyl) cyclo Rohexi 1 2 —Ethyl ester ester, 4-hydroxy 2 — (4 Bromofeni ) Cyclohexyl 2-ethyl ester ensulfonate, 4-hydroxy 1-2-(4-hydroxy phenyl) cyclohexyl 2-enthulfon Ethyl ester, 2 — (4-pyridyl) — 4 — Hydroxycyclohexyl 2 — Encarponic acid ester, 2 — (3 — pyridyl) 14 — Hydroxycyclohexyl 2 — Ethyl carboxylate, 2 — (2 — Pyridyl) 1 4 — Hydroxycyclohexyl 2 — Ethylester carboxylate, 2 — (2-Nitro-5 — Pyridyl) 1-4 —Hydroxycyclohexyl 2 — Enethylester, 2 — (2 1-chloro-5-pyridyl) 1-4-hydroxycyclohexyl 1-2-ethyl carbonate ester, 2- (2-methoxy-5-pyridyl) ) _ 4-Hydroxycyclohexyl _ 2-Ethyl ester of encarponic acid, 2-(5-Pyrimidinyl) 1-4-Hydroxycyclohexyl 2 — Ethyl carboxylate, 2 — (122-to-5-pyrimidinyl) 1-4-Hydroxy-cyclohexyl 2-—Ethyl carboxylate, 2 — (2 — Chloro 5 — pyrimidinyl) 1-4-Hydroxycyclohexyl 2 _ ethyl carboxylate, 2 — (2 — Methoxy 5-pyrimidinyl) 1-4-hydroxycyclohexyl-2-ethyl carboxylate, 2-(4-pyridyl) 1-4-hydroxycyclohexyl 1-2-encyclopedia, 2-(3-pyridyl) 14-hydroxy Cyclic hex 1-2-encarponitrile, 2-(2-pyridyl) 1-4-Hydroxyl hex 2-encarbine 2 — (2 — 2 1 5 — pyridyl) 1 4 — Hydroxycyclohexyl 2 _ encapsulated 2, 2 — (2 — Black mouth — 5 — pyridyl) 1-4 —Hydroxycyclohexyl 2 — encarponitrile, 2 — (2 — methoxy-1 5 — pyridyl) 1-4 — Hydroxy 1 2 — Enchanted bottle, 2 — (5 — Pyrimidinyl) 1-4-Hydroxy cyclohexyl 1-Encalponitrile, 2-(2-Nitro 1-5-Pyrimidinyl) 14- Hydroxy Cyclo 1-2-ene carbitol, 2-(2-Chloro 5-pyrimidinyl) 1 4-Hydroxy Xy 2—Encarbyl Tril, 2— (2—Methoxy 5—Pyrimidinyl) 1-4—Hydroxy Cyclohexy 2—Enka Rubinitrile, 2 — (4 — pyridyl) 1 4 — Hydroxyl cyclohexyl 1-2 1-Ethyl sulfonate, 2 — (3 — pyridyl) 1-4-Hydroxycyclohexyl 1-2-Ethyl sulfonic acid ester, 2-(2-pyridyl) 1-4-Hydroxylcyclohexyl 2 one 2-Sulfonic acid ethyl ester, 2 — (2—Nitro-5—Pyridyl) 1-4 — Hydroxycyclohexyl 1-2 — Ensulfonate ethyl ester, 2 — ( 2 — chloro 5 — pyridylyl) 1-4 4-hydroxy cyclohexyl 2 — ethyl esulphonate, 2 — (2 — methoxy 5 — pyridyl) ) _ 4 1-Hydroxycyclohexyl 1-2-Ethyl ethyl ester, 2-(2-Amino 5-pyrimidinyl) 14-Hydroxy 2-hexyl ester, 2-hexyl ester, 2- (2-nitro-5-pyrimidinyl) -14-hydroxycyclohexyl-2—ensuron Ethyl ester, 2 — (2 — Black mouth 5 — Pyrimidinyl) 1-4-Hydroxycyclohexyl 1-2 1 -Ethyl ethyl ester, 2 — (2 — Toxic 5-pyrimidinyl) 1-4-hydroxycyclohexyl 2-ethenyl ester ensulfonate.

Preferred compounds of the general formula (7) include: 41-chloro-2_phenylcyclohexyl-2-ethylencarbyl ester, 41-chloro 2 — (4 — methylphenyl) cyclohexyl 2 — enethyl carboxylate, 4-chloro 2 — (412 mouth phenyl) cyclohexyl Ci-2—Ethylester carboxylate, 4—Cro mouth 1-2— (4—Methoxy sulfide) Cyclichexi1-2—Ethylester enecarbonate, 4-Chloro 2— (4-Chlorophenyl) Cyclohex 1-2—Ethyl carboxylate ester, 41-Chloro 2— (4—Bromov Enyl) cyclohexyl-2- (2-ethylencarboxylate), 4- (chloro-2) (4—hydroxy (Phenyl) cyclohexyl 2—ethyl ester carboxylate, 41-chloro-2—phenyl cyclohexyl 2—methyl ester phenyl carboxylate, 4—h B mouth 1 2 — (41 methyl phenyl) cyclohexyl 1 2 — methyl carponic acid Sterol, 41-chloro-2— (412-trophenyl) cyclohexyl-2-ene methyl carbonate, 41-cro-mouth 1-2— (4— (Methoxy phenyl) Cyclohexyl 2—Methyl ester of encarponic acid, 4—Chloro 2— (41 crocl phenyl) Cyclohexyl 2—Methyl carboxylate, 4—Chloro-2- (4-bromophenyl) cyclohexyl —2—Methyl ester carboxylate, 4—Chloro Row 2 — (4-Hydroxyphenyl) cyclohexyl 2 — Methyl ester of encarponic acid, 41 1 2 — Phenyl cyclohexyl 2 — Encapsulated Tril, 4 — Black Mouth 1 — — (4 — Methyl phenyl) Cyclohexyl 1 — Enchal 2-tril, 41-chloro-2 — (4—nitrophenyl) cyclohexyl 1—encarbon tril, 4—chloro2— ( 4 — methoxyphenyl) cyclohexyl — 2 — encarponitrile, 4 — chloro-2 — (4 — phenyl) cyclohexyl 2 — Encarbonitrile, 41 chrome mouth 2 — (4 — Bromophenyl) cyclohexyl 2 — Encarbonitol tril, 41 chloroー 2 — (4-Hydroxy phenyl) Cyclohexone 1 — Encarbon tril, 41 口 1 2 — Phenylcyclohexyl 2 — Ensyllefonic acid ethyl ester, 41 ク 1 2 — (4 — methyl efirile) Cyclohexyl-2-enesulfonate, 41-Chloro2— (4—nitrophenyl) Cyclohexyl_2—ethylsulfonate Ter, 41-chloro-2— (4-methoxyphenyl) cyclohexyl-2-enesulphonic acid ester, 4—cycloethyl 1-2— (4-chloro Mouth phenyl) Cyclohexyl 2—Ethyl sulfonic acid ester, 41 cro Mouth 1— (4—Bromophenyl) Cyclohexyl 2—Ensulfone Acid ethyl ester, 41-chloro mouth 1 2 — (4—hydroxy phenyl) cyclohexyl 1 2 — Ensulfonate ethyl ester, 41-methyl sulfonic acid 1 2 — phenylcyclohexyl 2 — ethyl carbene ester, 4 _ Tansulfonyloxy 1-2-(4-methylphenyl) cyclohexyl 2-ethyl carboxylate, 4-Metatansulfonyloxy 1--( 4 — Nitrophenyl) Cyclohexyl 2 — Ethylene carboxylate, 41-Methanesulfonyloxy 1 2 — (4 — Methoxyphenyl) ) Cyclohexyl-2-ethyl ether ester, 4—Methanesulfonyloxy1-2— (41-crop phenyl) Cyclohexyl-2-ene Ethyl carboxylate, 4 — methane sulfonyloxy 2 — (4 — bromophenyl) cyclohexyl 2 — Ethyl carboxylate, 4—Methanesulfonyloxy 1- 2— (4—Hydroxyphenyl) Cyclohexyl 1-2—Ethyl carboxylate , 4 — methanesulfonyloxy 2 — phenylcyclohexyl 2 — methyl phenyl carboxylate, 4 — methansulfonyloxy 1 2 — (4 (Methyl phenyl) cyclohexyl-2--methyl ester of carboxylic acid, 41-methanesulfonyloxy 1-2 (-412 phenylphenyl) Hexyl 2 — methyl ester of carboxylic acid, 4-methyl sulfonyloxy 2 — (4 — methanol) cyclohexyl 1 — 2 Methyl carbonyl ester, 41-methyl sulfonyloxy 2 — (4 — phenyl chloro) cyclohexyl 2 — methyl carboxylic ester, 41 methansulfonyloxy 2 — (4 bromophene) Nil) Cyclohexyl 2 — methyl carboxylate, 4 — methane sulfonyloxy 1 — 2 — (4 — hydroxyphenyl) cyclohexyl 2 — methyl ethyl ester, 41 methansulfonyloxy 2 — phenylcyclohexyl 2 — phenyl carbonyl, 4 — methansulfonyl Xy2 — (4 — methylphenyl) cyclohexyl2 — encarponitrile, 41 methansulfonyloxy 2 -(412 trophenyl) cyclohexyl 1-2-phencarbonyl, 41-methane sulfonyloxy 1-2-(4-methoxyphenyl) cyclo Hexa 2-phenyl carnitrile, 41 meth- yl sulfonyloxy 1-2-(41 cro-mouth phenyl) cyclohexyl 2-enca Luponitrile, 4 — methanesulfonyloxy — 2 — (4 — bromophenyl) cyclohexyl 1 — enecarnitrile, 4 — methansul Phenyloxy 2-(4-Hydroxyphenyl) Cyclohexyl 2-Encapsulitol, 41 Eninolecyclohexyl 2—Ethyl sulfonate, 4—Methanesulfonyl XII 2 — (41-methylphenyl) cyclohexyl 2 — ethylsulfonate ester, 4 — methansulfonyloxy 1 2 — (412 trifluorophenyl) ) Cyclohexyl 2-ethyl sulphonate, 4-methansulfonyloxy 1-2-(4-methoxyphenyl) cyclohexyl 1- Ensulfonate ester, 41-Methanesulfonyloxy 1- 2-(4-Chlorophenyl) cyclohexyl 2-Ensulfonate ester, 4 1-Methanesulfonyloxy 1- 2-(4-Bromophenyl) cyclohexyl 2-Enethyl sulfonate, 4-Meta 1 2 — (4-hydroxyphenyl) 1 2-(4-pyridyl) 1-enethyl sulfonate, 2-(4-pyridyl) Chlorocyclohexyl 1-2-ethyl carboxylate, 2-(3-pyridyl) 14 1 Chlorocyclohexyl 1-2-ethyl carboxylate Ter, 2 — (2 — pyridyl) — 4 — Chlorocyclohexyl 2 — Ethyl carboxylate, 2 — (2 — Nitro 1 — Viridylile) 1—4—Kroxy 1—2—Ethylene carboxylate ester, 2— (2—Kro mouth 1—Pyridyl) 1—41ー 2 — Ethyl ester of encarponic acid, 2 — (2 — Methoxy 5 — Pyridyl) 1-4 2-hexyl carboxylate 2- (5-pyrimidinyl) -141 chlorocyclohexyl 2—ethyl carboxylate, 2— (2—Nitro-5—Pyrimidinyl) _4—Chlorocyclohexyl 2—Enecarboxylate ester, 2— (2—Chloro5— Pyrimidinyl) 1-4 -Chlorocyclohexyl 1-2-ethyl ethyl ester, 2-(2-methoxy-15-pyrimidinyl) 14-Chloro Cyclohexyl _ 2 — ethyl carboxylate, 2 — (4 — pyridyl) — 4 — chlorocyclohexyl 2 — encarbonitrile, 2 — ( Three 1-Pyryl) 1 4—Chlorocyclohexyl 2—Genecarbonitrile, 2— (2—Pyridyl) 14 1 Chlorocyclohexyl 2— Encarbon tril, 2 — (2—2 trough 5 — pyridyl) 14 1 Chronocyclohexyl 2 — Encarbon tril, 2 — (2—Black mouth 1—5—Pyridyl) 14—1 Black chrome 1—2—Encyclopedia, 2— (2—Methoxy 1—5—P (Rizil) _ 4 — Chromocyclohexyl 2 — ene carboxyl, 2 — (5 — pyrimidinyl) 14 1 Chromocyclohexyl 1 2 — Encarbonitrile, 2 — (2-2-Tro 5-Pyrimidinyl) 1-4-Chlorocyclohexyl 2-Encarbonitril, 2-(2- Black mouth _ 5 — (Mizinil) 14 1 Chromocyclohexyl 1-2-encapsulitol, 2-(2-methoxy 1-5-pyrimigel) 14-chloro Cyclohexyl 2 — encarponitrile, 2 — (4-pyridyl) 14 — chlorocyclohexyl 2 — ethylsulfonate ester, 2 — (3—Pyridyl) 14 1 Chlorocyclohexyl 2 _ Ensyl sulfonate ester, 2 — (2—Pyridyl) 14 — Chlorocyclo 2- (2-ethyl-5-pyridyl) -14-chlorocyclohexyl-2— (2-ethylhexyl ester) 2 — (2 — Black mouth _ 5 1-Pyridyl) 1-4—Chlorocyclohexyl 1—2—Ethyl ester sulphonate, 2— (2—Methoxy 5—Pyridyl) Chromohexi 2-enethyl sulfonate, 2- (2-amino 5-pyrimidinyl) 1-4 chloro cyclohexyl 2-enethyl esulphonate Ter, 2 — (2 — nitro-5-pyrimidinyl) -14 — chlorocyclohexyl _ 2 — ensulfonate ethyl ester, 2 — (2 — cro 5 — pyrimidinyl) 14 1 Chlorocyclohexyl 1 2 — ethylsulfonate ester, 2 — (2 — methoxy 1 5 — pyrimidinyl) 1 4 1 Chlorocyclohexyl-2-ethyl enethyl ester and the like.

Preferred compounds represented by the general formula (8) include 2-phenylhexaethyl-1,3-diethyl carboxylate and 2- (4-methylphenyl) cyclohexane (B) Hexahexyl 1, 3 — Jenethyl carboxylate, 2 — (4 — Nitrophenyl) Cyclohexa 1, 3 — Jencarboxylate, 2 _ (4 — Toxic phenyl) Cyclohexa-1,3—Ethylene carboxylate ester, 2— (41-crop phenyl) Cyclohexa-1,3—J Nethyl carboxylate, 2 — (4 — Bromo C) Cyclohexa-1,3—Genethyl carboxylate, 2— (4-Hydroxyphenyl) Cyclohexa1,3, —Genethyl carboxylate , 2 — phenylcyclohexa 1, 3 — methyl carbene ester, 2 — (4 — methyl phenyl) cyclohexa 1, 3, 3 — methyl phenyl carbonate Ter, 2 — (4-dinitrophenyl) cyclohexene 1, 3 — Methyl ester of gen carbonate, 2 — (4-methoxyphenyl) cyclo Hexa 1,3—Methyl ester of Jencarbonate, 21 (41-Mouth phenyl) Cyclohexa 1,3—Methyl ester of Jenn carbonate, 2— ( 4 Bromophenyl) Cyclohexa 1, 3 — Jenka 2- (4-hydroxyphenyl) cyclohexyl 1,3—methyl phenyl ester, 2—phenylcyclohexyl 1 , 3 — Jen carbonitrile, 2- (4-methyl phenyl) cyclohexa — 1, 3 — Jen carbonitrile, 2 — (412 trophen) Nil) Cyclohexa 1, 3 — Jennical porphyrin, 2 — (4-Methoxy phenyl) Cyclohexa 1, 3 — Jencarbyl Lily, 2 — (4 — phenyl) cyclohexene 1, 3 — Jencarbyl tril, 2 — (4 — bromophenyl) cyclohexa -1, 3 — Jenniferous lipotrile, 2 — (4-hydroxy hydrazine) cyclohexane 1, 3 — Jen carbitol tril, 2 — F Cyclohexene 1,3—ethyl sulphonate ester, 2— (4-methyl phenyl) Cyclohexa 1,3—ethyl hexyl ester, 2— ( 4 12-Trophenyl) cyclohexa — 1, 3 — ethylsulfonate ester, 2 — (4-methoxyphenyl) cyclohexa 1, 3 — die 2,3- (4-chlorophenyl) cyclohexa-1,3-diene sulfonate, 2-((4-bromophenyl) cyclohexane 1-, 3--Diethyl sulfonate ethyl ester, 2- (4-Hydro 1,3-cyclohexene-1,3-diethyl sulfonate, 2- (4-pyridyl) -1,3, cyclohexene-ethyl carboxylate, 2 — (3 — pyridyl) 1 1, 3 — cyclohexene gencarbyl ester, 2 — (2 — pyridyl) 1, 3 — Ethyl ester, 2— (2—Nitro-5—pyridyl) 1-1,3—Cyclohexagene carboxylate, 2— (2—Cro mouth—5—Pyryl Jill) 1, 3 — Cyclohexagene ethyl ester carbonate, 2 — (2 — Toxican 1-5—Pyridyl) 1,3—Cyclohexadienene carboxylate ester, 2— (5—Pyrimidinyl) 1-1,3—Cyclohexagen Ethyl carboxylate, 2— (2—nitro-5—pyrimidinyl) 1-1,3—cyclohexagene ethyl ester carboxylate, 2— (2—chloro-5— Pyrimidinyl) — 1, 3 — cyclohexene gencarboxylate, 2- (2 — methoxy 5 — pyrimidinyl) 1, 3 — cyclohexadenyl Ethyl ester of carbocarbonate, 2 — (4 — pyridyl) 1, 3 — cyclohexagene carbonitrile, 2 — (3 — pyridyl) 1 1, 3 — cyclo Hexagen carbonitrile, 2 — (21 pyridyl) 11, 3 — cyclohexyl Jefferies down carboxymethyl two door Li Le,

2-(2-2-Tro 5-pyridyl) 1 1, 3-Cyclohexadiene carnitrile, 2-(2-Chloro 5-pyridyl) 1 1 ,

3 — Cyclohexagen potassium nitrile, 2 — (2 — methoxy-5-pyridyl) 1-1, 3 — Cyclohexagen potassium nitrile, 2 — (5—pyrimidinyl) 1-1,3—cyclohexadiene trinitrate, 2— (2—two-tro-5—pyrimidinyl) -1,3— Cyclohexadiene Carbonitrile, 2 — (2 — Chloro 5 — Pyrimidinyl) 1 1, 3 — Cyclohexadiene Carbonite Lilyl, 2 — (2 — methoxy 5 — pyrimidinyl) _1, 3 — cyclohexagencarbone tril, 2 — (4 1 pyridyl) 1 1 , 3 — cyclohexadiene sulfonate ester, 2 — (3 — pyridyl) 1-1, 3 — cyclohexadiene sulfonate ester, 2 — (2 Jill) 1, 1-3-cyclohexene gensulfonate, 2-(2-2 tro 5-pyridyl) 1, 1-3-cyclohexadienesulfonate Ter, 2- (2—chloro-5—pyridyl) 1-1,3—cyclohexadienesulfonate ethyl ester, 2— (2—methoxy-5—pi (Rizil) 1, 3 — Cyclohexadienence ethylester sulfonate, 2 — (2 — Amino 5 — Limidinyl) 1, 3 — Cyclic mouth hexadiene sulphonate ester, 2 — (2 — nitro 1 5 — pyrimidinyl) 1, 3 — Cyclohexadiene sulpho Ethyl ester, 2- (2-chloro-5-pyrimidinyl) 1-1,3—Cyclohexadienes ethyl ester sulfonate, 2— (2—Methoxy 5— Pyrimidinyl) 1,1,3-cyclohexadiene sulfonate and the like.

Preferred compounds of the general formula (9) include biphenyl 2—ethyl carboxylate, 4′—methyl biphenyl 2—force Ethyl Luponate, 4 '-Nitrobiphenyl 2-Ethyl Carbonate, 4'-Chlorobiene 2-Power Ethylester, 4 ' — Promobiphenyl 2 — Ethyl ester of carboxylate, 4 '— Hydroxybiphenyl. 2 — Ethyl ester of carboxylate, Biphenyl 2 — Power Methyl ester, 4 '-methyl biphenyl 2-methyl ester carbonate, 4'-Nitro biphenyl 1-2-methyl ester carbonate, 4 ' 1-chlorobiphenyl 2-methyl carboxylate ester, 4'- Bromobiphenyl 2 _ carboxylic acid methyl ester, 4 '- Hydroxy-biphenyl 2 — Methyl les-terbiphenyl 2 — Power Polytrile, 4'-methyl biphenyl 1-2 -Carbon tril, 4 '-12 Bi-biphenyl 2 -Carbo tril, 4'-Cro Robi-Fu-Ri-Lu 2 — Power Lupo-Tri-Lu, 4'-Bro-Mobi-Fu-Ri-Lu 2 – Calbo-Tri-Lu, 4'- —Carbonitrile, biphenyl 2—ethyl sulphonate, 4'—methyl biphenyl 2—ethyl sulphonate, 4′12 Ru 2 —Sulfonate ethyl ester, 4'-Chlorophenyl 1-Sulfonate ester, 4'-Bromobiphenyl 2 —Ethyl sulfonate Estel, 4'-Hydroxybiphenyl-1 2-Ethyl sulfonate, 4- (2-ethoxycarbonylphenyl) pyridine, 3- (2-D Toxicarponylphenyl) pyridine, 2 — (2 — ethoxycarponylphenyl) pyridine, 2 — nitro5-(2 — ethoxycarbonylphenyl) pi Lysine, 2—chloro-5— (2—ethoxycarbonylphenyl) pyridin, 2—methoxy5— (2—ethoxycarbonylphenyl) pyridin, 5 — (2 — ethoxycarponylphenyl) pyrimidin, 2 — nitro-5 — (2 — ethoxycarponylphenyl) pyrimidin, 2 — black mouth One 5 — (2 — ethoxycarponylphenyl) bilimidine, 2 — methoxy Si 5 — (2-ethoxycarponylphenyl) pyrimidine, 4 — (2-cyanophenyl) pyrimidine, 3 — (21-cyanophenyl) pyrimidine Pyridine, 2 — (2 — cyanophenyl) pyridine, 2 — nitro 5 — (2 — cyanophenyl) pyridine, 2 _ Cyanophenyl) pyridin, 2—Methoxy 1-5— (2—Cyanophenyl) pyridin, 5— (2—Cyanophenyl) pyrimidine Gin, 2—Nitro 5— (2—Cyanophenyl) pyrimidine, 2—Cro mouth 5— (2—Cyanophenyl) pyrimidine, 2—Methoxy 5— (2—Cyanophenyl) Mizine, 4- (2-ethoxysulfonylphenyl) pyridin, 3- (2—ethoxysulfonylphenyl) pyridin, 2— (2-ethoxyxyl) 2-phenyl-2-phenyl-5- (2-ethoxyethoxyphenyl) pyridine, 2-chloro-5— (2— Ethoxysulfonylphenyl) pyridine, 2 — methoxy 5 — (2 — ethoxysulfonylphenyl) pyridine, 5 — (2 — ethoxysulfonyl) Onylphenyl) pyrimidine, 2—nitro-5_ (2—ethoxysulfonylphenyl) pyrimidine, 2—chloro-5— (2 — Ethoxysulfonylphenyl) pyrimidine, 2 — methoxy 5 — (2 — ethoxysulfone) Etc. Ruch enyl) a pin Li Mi di emissions can be mentioned, et al. Is Ru.

Preferred compounds of the general formula (10) include 2— (4—pyridyl) -12,4—cyclohexagene ethyl ester carbonate and 2— (3—pyridyl) 1, 2, 4-cyclohexagen carboxylate ester, 2-(2-pyridylyl) _ 2, 4-mouth mouth hexadiene carboxylate ethyl ester, 2 _ ( 2—Nitro-5—pyridyl) 1-2,4—Cyclohexagen carboxylate ethyl ester, 2— (2—Cro mouth-1-5—pyridyl) 1-2,4— Cyclohexagene ethyl ester carbonate, 2 — (2 — Toxican-5-pyridyl) 1-2,4-cyclohexadiene carboxylate ester, 2— (5—pyrimidinyl) 1-2,4—cyclohexadieneca Ethyruster ester, 2-((2-Nitro-5-pyrimidinyl) 1,2,4—Cyclohexadiene ethyl ester ester, 2— (2—Chloro-5— Pyrimidinyl) 1,2,4-cyclohexadiene carboxylate, 2- (2—methoxy-15-pyrimidinyl) 1-2,4-cyclohexadiene Ethyl carboxylate, 2— (4—pyridyl) -1,2,4—cyclohexadiene carbonitrile, 2— (3—pyridyl) 1-2,4—Si Cyclohexadiene carnitrile, 2 — (2 — pyridyl) 1, 2, 4 — cyclohexyl Jencarponitrile, 2— (2—Nitro-5—Pyridyl) -1,2,4—Cyclohexadiene Carponitrile, 2— (2—Cro 5 _ pyridyl) 1, 2,4-cyclohexadiene carboditrile, 2-(2-methoxyl 5-pyridyl) 1, 2,4-cyclohexadiene 2-4 (5-Pyrimidinyl) -1,2,4-cyclohexadiene triol, 2— (2—Nitro-5-pyr (Midinyl) 1, 2, 4-cyclohexadiene potassium nitrile, 2-(2-chloro 5-pyrimidinyl) 1, 2, 4-cyclohexadiene Carponite Lilyl, 2 — (2-methoxy-5-pyrimidinyl)-1, 2, 4-cyclohexagencalponitril, 2-(4-pyridyl)-1, 2, 4-cyclohexadiene sulphonate ethyl ester, 2 — (3 — pyridyl) one 2,4 — cyclohexadiene sulphonate ethyl ester, 2 — (2 — pyridyl) 1, 2, 4-cyclohexagenesyl ethyl ester sulfonate, 2-(2-nitro 1-5-pyridyl) 1, 2, 4-cyclohexadienesulfonate ethyl ester, 2— (2—Cro- mouth 1—Pyridyl) 1—2,4-Cyclohexadiene sulphonate ester, 2— (2—Methoxy 5—Pyridyl) 1 2, 4 — cyclohexadiens ethyl ester of sulfonate, 2 — (2 — amino 5 — pyriyl Dinyl) 1, 2, 4-cyclohexadiene sulfonate ethyl ester, 2 — (2-nitro 1-5-pyrimidinyl) 1, 2, 4 — cyclohexadiene sulfonate ethyl ester , 2 — (2 — cromo 1-5 — pyrimidinyl) 1-2, 4 — cyclohexadiene sulphonate ester, 2 — (2 — methoxy 5 — pyrimidinil) 1) 2,4-cyclohexadiene sulfonate ethyl ester.

Preferred compounds of the general formula (11A) include 3—chloro2_phenylcyclohexa 2,4—ethyl ethyl carboxylate Estel, 3-Black mouth 2-(4-methyl phenyl) Cyclohexane 1, 2, 4-1-ethyl ether ester, 3-Black mouth-2-(4- Nitrophenyl) cyclohexa 2,4—Genethyl ester carbonate, 3—Cro mouth 1 2— (4—Methoxyphenyl) cyclohexa 1 2 , 4 — Ethylene carboxylate, 3 — Black mouth 2 — (4-1 phenyl) Cyclohexa 1, 2, 4 — Ethylene carboxylate, 3 — Black mouth 2 — (4 — Bromophenyl) cyclohexa 1,2,4-Genoyl ethyl ester of carboxylic acid, 3 — Black mouth 1 2 — (4-hydroxy phenyl) Nil) Cyclohexa 2,4 1-gen ester eruponic acid ester, 3—Cro mouth 1 2— Enylcyclohexa 2,4-Methyl ester of carboxylate, 3—Chloro 2— (4—Methylphenyl) cyclohexa 2,4—J Methyl ester of carboxylic acid, 3 — chloro 2 — (4 — nitrophenyl) cyclohexa 2,4, methyl ester of di carboxylic acid, 3 — Black mouth-2-(4-Methoxysilane) Cyclohexa 2, 4 — methyl ester of gencarponic acid, 3 — Black mouth 1 2 — (4 — 2,4-cyclohexene 2,4-methylene methyl ester, 3-chloro-2- (4-bromophenyl) cyclohexyl 1,2,4—Methyl ester of jencarbonate, 3—Chloro2— (4-Hydroxyphenyl) cyclohexane 2,4—Jencarboxylate Methyl ester, 3 — Black mouth 1 2 — Fenirsk hex 2, 4 — Jen carbitol, 3 — Black mouth 1 2 — (4 — Methyl phenyl) Hexane 2 and 4 1-gen power rutile, 3—Cro mouth 1 2 — (412 trophenyl) Cyclohexa 12 and 4 1-gen power report 2 Tril, 3 — Chlorine 2 — (4 — Methoxyphenyl) Cyclohexa 1, 4, 1 Jencarbon tril, 3 — Chloro mouth 1 2 — ( 4 — black mouth phenyl) cyclohexa 1, 4 — gen carbitol, 3 — chloro 2 — (4-bromophenyl) Chromo-hexa 2, 4-1-gen carbotrile, 3-chloro 2-(4-hydroxyphenyl) cyclo-hexa 2, 4-gen 3 chloro-2-hexyl 2,4-diethyl sulfonate, 3—chloro 2 -— (4—methyl Enyl) cyclohexa 2,4-diene sulphonate ester, 3—cyclo 1,2— (412 trophenyl) cyclohexa 1,2,4—die Ethyl sulfonate, 3 — Black mouth 2 — (4-Methoxy phenyl) Cyclohexa 2, 4, 4-Diethyl sulfonate, 3 — Chlorolo 2 — (4 — Chlorohexyl) Cyclohexa 2, 4 — Diethyl sulfonate ester, 3 — Chloro 2 — (4 — Bromophenyl ) Cyclohexa 2,4-diethyl sulfonate, 3-Chloro 2-(4-hydroxyphenyl) Cyclohexa 2, 4-Diene Ethyl sulfonate, 2- (4-pyridyl) 1-41-Chloro 2,4—cyclohexagene ethyl ester carboxylate, 2_ (3-pyridyl) 1-4 2-, 4-cyclohexa- genogen carboxylate ester, 2-((2-pyridyl) -14-chloro-2,4-cyclohexadiene carbonyl Acid ethyl ester, 2 — (2 — nitro-5 — pyridyl) — 14 — black mouth — 1, 2, 4 2-cyclohexene ethyl carboxylate, 2- (2-chloro-5-pyridyl) -14-chloro-1,2,4-cyclohexagen-ethyl carboxylate , 2 — (2 — methoxy-5-pyridyl) 14-cro-1, 2, 4-cyclohexagene ethyl ester carbonate, 2-(5-pyrimidinil) 1) 4-chloro-2, 4—cyclohexenegen ethyl ester carbonate, 2 — (. 2—2-nitro-5—pyrimidinyl) 2,4-cyclohexageneethyl carbonate ester, 2- (2-chloro-5-pyrimidinyl) 1,2,4-cyclohexagen ester ethyl ester carboxylate, 2— (2—methoxy-15—pyrimidinyl) 14,41 mouth 1,2,4-cyclohexadiene Ethyl carboxylate, 2— (4-pyridyl) -1 4—Chloro2,4-cyclohexa-gengen-calponitrile, 2— (3—pyridyl) -1 41-chloro-2,4-cyclohexadiene carbonyl, 2-((2-pyridyl)) 1-41-cyclo2,4-cyclohexadiene 2nd tril, 2—

(2—Nitro-5—Pyridyl) 1-4—Chloro2,4—Cyclohexagen carbitol, 2— (2—Chloro5—Piryl (Jil) 14-Chloro-2, 4-cyclohexadiene calporitrile, 2 — (2—Methoxy 5—Pyridyl) 14—Chloro 2 , 4 — cyclohexagen calponitrile, 2 — (5 — pyrimidinil) 14 1-mouth 1, 2, 4 cyclohexagen calponitril, 2 — (2-2 1-5-pyrimidinyl) 1 4 1

2, 4—cyclohexadiene carbonyl, 2 _ (2—chloro 5—pyrimidinyl) 1-4 4—cyclo mouth 1, 2, 4—cyclohexadiene 2-(2-Methoxy 1-5-pyrimidinyl)-1-4-Black mouth 1-2, 4-Cyclohexane , 2 — (4 — pyridyl) 1 4 1 chrome 2, 4 — cyclohexyl Ethyl ester of sodium sulphonate, 2 — (3 — pyridyl) 14 1 ク 1, 2, 4 — Cyclohexadiene sulfonate ester, 2 — (2 — pyridyl) 1 4 — Black mouth 1, 4 — Cyclohexadiene sulphonate ethyl ester, 2 — (2 — nitro 5 — pyridyl) 1-4 — Black mouth 1, 4 — 6 Lohexadienes ethyl ester sulfonate, 2 — (2 — Chlor 5 — pyridylyl) 1 4 — Chloro 2, 4 — Etyl ester cyclohexadienesulfonate, 2 — (2—Methoxy 5—Pyridyl) 1 4—Cross mouth 2,4—Cyclohexadiene sulphonic acid ethyl ester, 2- (2—Amino 5—P (Limidinyl) 141-chloro-2,41-cyclohexadiene-ethyl sulfonate Estel, 2 — (2 — Nitro _ 5 — Pyrimidinyl) _ 4 — Black mouth 2, 4 — Cyclohexadiene sulphonate ethyl ester, 2 — (2 — Rollo 5—pyrimidinyl) 1—4—Chloro2,4—Cyclohexadienesulfonate ethyl ester, 2— (2—Methoxy-1-5—pyrimidinyl) 1) 4-chloro-2,4-cyclohexadiene sulfonate and the like.

Preferred compounds of the general formula (11B) include: 3_cycloalkyl 12-phenylcyclohexane 1,3—ethyl gencarboxylate Estel, 3 — chloro-2 — (4-methylphenyl) cyclohexa 1, 3 — gen-carboxylate ethyl ester, 3 — cromouth — 2 — (412 1,3-cyclohexyl-1,3-cyclohexylester, 3-cyclohexyl-ethyl ester, 3-cyclohexyl-2- (4-methoxyphenyl) cyclohexene 1, 3 — Jenronic acid ethyl ester, 3 — Black mouth 1 2 — (4 — Black mouth fenirile) Cyclohexa 1, 3 — Jencarponic acid ester, 3 — Chlorolo 2 — (4 — Bromophenyl) Cyclohexanol 1, 3 — Gen-ethyl ether ester, 3 _ Chlorol 2 — (4 — Hydro Xyphenyl) Cyclohexa-1,3—Genol ester ester, 3—Chloro2— Phenylcyclohexars 1, 3 — methyl ester of diencarponic acid, 3 — Chloro 2 — (4-methylphenyl) cyclohexayl 1, 3 — Methyl ester of jencarboxylate, 3 — chloro-2 — (4 — nitrophenyl) cyclohexane 1, 3 — methyl ester of jencarboxylate, 3-Black mouth-2-(4-methoxyphenyl) Cyclohexa 1, 3 — Methylester gencarboxylate, 3 _ Chloro 2 — (4 — Cyclohexyl 1,3-cyclohexyl methacrylate ester, 3—Chlorol 2— (4—Bromophenyl) cyclohexyl 1, 3 — methyl carbonate methyl ester, 3 — chloro 2 — (4-hydroxyphenyl) cyclohexa 1, 3 — methyl carboxylic acid Chillester, 3 — Black mouth 2 — Fernix mouth 1, 3 — Jennium power, 3 — Black mouth 1 2 — (4-methylphenyl) Cyclohexa-1,3—gen power, 3—crop mouth 2— (412 trophenyl) cyclohexa-1,3—gen power Luponitrile, 3 — Chlorine 2 — (4-methoxyphenyl) Cyclohexa-1, 3 — Gen-force Lutonitrile, 3 — Chloro 2 — (4 — Black mouth phenyl) Cyclohexa 1, 3 — Jennium power tril, 3 — Black mouth 1 2 — (4 — Bromophenyl Cyclohexa 1, 3 — Genotropin tril, 3 — Kuro mouth 1 2 — (4 — Hydroxyphenyl) Cyclohexa 1, 3 — Gen-Kali Repot Nitrile, 3—Kuro mouth 1—2—Frenylcyclohexene 1, 3—Diethyl sulfonate ethyl ester, 3—Chloro 2— (4—Metyl fu Nyl) cyclohexa-1,3-diene sulfonate ethyl ester, 3—chloro-2— (412-trifluorophenyl) cyclohexa-1,3-diene sulfo Ethyl ester, 3—Chloro 2— (4-Methoxy phenyl) cyclohexa 1,3—Ethylene disulfonic acid ester, 3 — Chloro-2 — (4 — phenyl) cyclohexa-1,3-diene sulphonic acid ester, 3 — kuroguchi 1 — — (4 — bromofu Nil) Cyclohexars 1, 3 — Diethyl sulfonate ester, 3 — Chloro 2 — (4 — Hydroxyphenyl) Cyclohexars 1, 3 — Ethylene disulfonic acid ester, 2- (4-pyridyl) -1 4-Chloro1,3—cyclohexageneethyl ester of carbonic acid, 2— (3—pyridyl) -1 4-Chloro-1,3-cyclohexagen ester ethyl carboxylate, 2— (2—pyridyl) -14,1-Chloro mouth 1,3—cyclohexaje Ethyl ester of carboxylic acid, 2 — (2 — 2-Tro 5 — Pyridyl) 14 1 Chlor 1, 3 — Cyclohexagene carboxylate ester, 2 — (2 — Kuro mouth 1 5 — pyridyl) _ 4 — chloro 1, 3 — Cyclohexagene ester carboxylate, 2-(2-methoxyl-5-pyridyl)-1-4-chloro-1,3-cyclohexagene carboxylate ester, 2-(5-bilimidinyl)-1- 4 — Black mouth 1, 3 — Cyclohexagene carboxylate ester, 2 — (2 — 2-Tro 5 — Pyrimidinyl) 14 1 Chloro 1, 3 — Cyclohexanegen ethyl ester carbonate, 2 — (2—chloro 5 _ pyrimidinyl) 1-4 — cyclo Rows 1 and 3 — cyclohexagene carboxylate ethyl ester,

2 — (2 — methoxy 1 5 — pyrimidinyl) 1 4 — black 1,

3—cyclohexagene ethyl ester ester carboxylate, 2— (4—pyridyl) 1-4—chloro-1,3—cyclohexanegen calponitrile, 2— (3-pyridyl) 14-1-mouth 1, 3-cyclohexagen-calponitrile, 2-(2-pyridyl) 14-4-mouth 1, 3 — Cyclohexadiene alcohol, 2 _

(2-Nitro-1-5-pyridyl) 1-4 Chlorine 1, 3-Cyclohexagene carnitrile, 2-(2-Cro-1-5-pyridyl) 1) 4-chloro-1, 3-cyclohexadiene calporitrile, 2-(2-methoxy 5-pyridyl) 1-4-cyclo 1, 3 — Cyclohexagen calponitrile, 2 — (5 — pyrimidinil) 1-4 — Chloro 1, 3 — Cyclohexagen calponitril, 2 — (2—2-Tro 5—Pyrimidinyl) 1—4—Chloro 1 and 3—Cyclohexadiene calporitrile, 2— (2—Chloro 5—P Limidinyl) 1 4 — Black mouth 1, 3 — Cyclohexacene carbonitrile, 2 — (2 — Methoxy 1 5 — Pyrimidinyl) 1 4 — Ro roー 1, 3 — Cyclohexyl gencarbone tril, 2-(4 ピ pyridyl) 1 4 1 chloro 1, 3 シ cyclohexyl Ethyl ester of sodium sulphonate, 2 — (3 — pyridyl) 1 4-1 Chloro 1, 3 — Cyclohexadiene ethyl ester of sulfonate, 2 — (2 — pyridyl) 1—4—Chloro 1 and 3—Cyclohexadienesulfonate ethyl ester, 2— (2—2—1—5—pyridyl) — 4 1—Chloro 1 and 3 — Cyclohexadienes ethyl ester sulfonate, 2 — (2—chloro 5 — pyridyl) — 4 1,4-cyclohexadienens ethyl ester sulfonate Ter, 2 — (2 — methoxy 1-5 — pyridyl) 1 -4 1-3, 3 — cyclohexadiene disulfonyl ethyl ester, 2-(2 — amino 1 5 — (Pyrimidinyl) 1 41 1 Cyclo mouth 1, 3 —cyclohexadiene ethyl sulfonate Stele, 2 — (2 — 2-Tro 5 — Pyrimidinil) 14 1 ロ 1, 1, 3 — Cyclohexadiene sulphate ethyl ester, 2 _ (2 — クRollo 5 — pyrimidinyl) 14 1 Black mouth 1, 3 — cyclohexadienence ethyl ester of sulfonate, 2 — (2 — methoxy 5 — pyrimidinil) 1) 4-chloro-1,3-cyclohexadiene ethylsulfonate.

Preferred compounds of the general formula (12) include 5—chlorobiphenyl-2—potassium ester, 5—chloro4′- Methyl biphenyl 1-2-ethyl chloride ester, 5-chloro 4 '12 Trobi phenyl 2-2-ethyl chloride ester, 5, 4'-dichloro Robiphenyl 2-ethyl propyl ester, 5-Chloro 4 '-Promo phenyl 1-2-ethyl propyl ester, 5-Chloro 4 '-Hydroxybiphenyl 1-yl ethyl ester, biphenyl 2—methyl carbonyl ester, 5—Cro-lipone 4'—methyl biphenyl Two-way 2 — Power methyl ester, 5 — Black mouth 4 '— Nitrobiphenyl 2 — Power sodium methyl ester, 5, 4' — Zikurorov Enyl-2-methyl ester of carboxylic acid, 5-black mouth 4 '-bromobiphenyl 2-methyl propyl ester, 5-chloro 4 '-hydroxy 2 2-methyl propyl ester, 5-chloro biphenyl 2 — Power reporter, 5 — Crawl 4 '— Methyl beef 2 Lou 2 — Carrepitol, 5 — Crop mouth 1 4 '12 Lou 2 — Carbonitrile, 5, 4 '— Dichlorobiphenyl 2 — Power Luponitrile, 5 — Kuroro 4' — Promolofenyl 1 2 — Carbonitrile, 5 — Chloro 4 '— Hydroxybiphenyl 2 _ Power Riponitrile, 5 — Chlorobiphenyl 2 — Sulfo Ethyl ester, 5 — Kroll 4 '-methyl biphenyl 2-sulfonate ethyl ester, 51-1 mouth 4'-nitrobiphenyl 2-sullyphonate ethyl ester, 5, 4 '- Dichlorobiphenyl-1 2—ethyl sulfonate, 5_chloro mouth 1'-Bromobiphenyl 1-2—ethyl sulfonate, 5—chloro 4 ' -Hydroxybiphenyl 2-Ethyl Sulfonate, 4- (4-chloro- mouth 1-21-ethoxycarbonylphenyl) Pyridin, 3-(4-Cro Mouth 2—ethoxycarponylphenyl) pyridin, 2— (4-chloro-12-ethoxycarbonylphenyl) pyridin, 2—2tro-5— ( 4 — Black mouth 2 — Ethoxycarbonylphenyl) pyridine, 2 — Black mouth 5 — (4 — Kuro mouth 1 2 — Ethoxycalireponyl phenyl) pyridin, 2 — Methoxy 1 5 — (4 — Chloro 2 — Ethoxycarbonyl phenyl) ) Pyridine, 5 — (4 — Kuro mouth 1 2 — Ethoxy karponylphenyl) Pyrimidin, 2 — N 2 mouth 1 5 — (4 — Chloro 2 — D) Toxylcarbonylphenyl) pyrimidine, 2—chloro-5— (4—black mouth_2—ethoxycarbonylphenyl) pyrimidine, 2—methoxy Si 5 — (41-ethoxy carbonyl phenyl) pyrimidine, 41 (4-chloro 21-cyanophenyl) pyrimidine, 3 — (4 — Roll 2 — Siano Phenyl) pyridin, 2 — (4-chloro-2 — cyanophenyl) pyridine, 2 — nitro-5 — (4 — chloro-2 — shear Nophenyl) Pyridine, 2—Black mouth 5— (41 Chlorine 2—Cyanophenyl) Pyridine, 2—Methoxy 5— (4 — Krollo 2 — Cyanophenyl pyridine, 5 — (4 — Kuroguchi 2 — Cyanophenyl) pyrimidine, 2 — Nitro 1 5 — (41-chloro-2—cyanophenyl) pyrimidine, 2—chloro-5— (4-1-chloro2—cyanophenyl) pyrimidine 2-, methoxy-5- (4-cyanophenyl) pyrimidine,

4- (4-chloro-2-phenylethoxyphenyl) pyridin, 3- (4-chloro-2-phenyl-2-ylphenyl) pyri 2-, 4- (2-chloro-2-phenyl) phenyl, 2--2-tro-5- (4-chloro-2-ethoxy) Thistle phenyl phenyl) pyridine, 2-chloro 5-(4-cro 1-2- ethoxysulfonyl phenyl) pyridine, 2-meth Xy 5-(4-Chloro 2-ethoxy sulfonylphenyl) pyridine, 5-(4-Chloro 2-ethoxy sulfonyl phenyl) ) Pyrimidin, 2-nitro 5-(4-chloro-2-phenoloxyphenyl) phenylimidine, 2-クMouth one 5 — (4-Cross mouth 1 2 — Ethoxysulfonylphenyl) pyrimidine, 2 — Methoxy 1 5 — (4 — Clos mouth 1 2 — Jet cis Levonylphenyl) pyrimidin and the like.

 In the present invention, the compounds represented by the general formulas (1) to (10), (11A), (1IB) and (12) include, for example, compounds such as hydrogen chloride and hydrogen bromide. Hydrogen hydride; other inorganic acids such as sulfuric acid, nitric acid, phosphoric acid; organic sulfonic acids such as methane sulfonic acid, p-toluene sulfonic acid; or triflic acid Although some salts can be formed using other organic acids such as chloroacetic acid and oxalic acid, these are also included in the present invention. . These can be used as an intermediate in the form of a salt or by neutralizing an acid.

In the present invention, the compounds represented by the general formulas (1) to (10), (11A), (1IB) and (12) include, for example, sodium salts and potassium salts. Metal salts such as magnesium salts, earth metal salts such as magnesium salts and calcium salts; transition metal salts such as copper salts and iron salts; Some salts form salts with salts, such as organic base salts such as ammonium salts and amine salts. These are also included in the present invention, and may be prepared by neutralizing a salt or a base by neutralizing the base. It can be provided as an interstitial body.

 In the present invention, general formulas (1) to (10), (11A),

The compounds represented by (1 IB) and (12) may have optical isomers, geometric isomers and tautomers, in which case the present invention relates to one isomer and several It also includes mixtures of isomers in any proportion. In addition, the general formulas (1) to (10) (11A)

Hydrates of the compounds represented by (11B) and (12) are also included.

 The reaction steps in the production method of the present invention are as follows:

[Synthetic route 1]

(1)

 (Five)

[Synthetic route 2]

 (5) (6) (7) (8) (9)

[Synthetic route 3]

(5) (6) (10) (9) [Synthetic route 4]

(Wherein X, indicating Y, Z, Q, W, R and R ³ also is given same as those defined above.)

 [Synthetic route 1]

 General formula (1) as starting material for this synthesis method

X

 0 '(1)

(Wherein X and Y are the same as defined above.) The ketone derivative represented by the formula is applied by applying a method such as J. Am. Chem. Soc. Can be synthesized by the general formula (2)

, 17, 809 (1987), Synth. Commun., 21, 271 (1991) and Tetrahedron Letters, 24, 3477.

(1983) can be synthesized by applying the general formula (3)

The compound represented in the Chemistry Letters, 1663 (1993) and _{Org. Syntheses Col 1. Vo 1 3} , 305 ∎ You can in this transgression be synthesized by applying the method such as (1955).

First step: Production of a compound of the general formula (4) from a compound of the general formula (1)

General formula (4)

(Wherein X, Y, R ¹ , and R ³ are the same as defined above). The compound represented by the general formula (1)

X

 0 '(1)

(Wherein X and Y are the same as defined above) or a salt thereof in a solvent in the presence or absence of a base in a solvent represented by the general formula (2):

(Wherein II ¹ and are the same as defined above)

(Wherein, II ¹ , R ^! R ³ and Z represent the same as described above).

 Solvents used in the above reaction include, for example, aliphatic lower alcohols such as methanol, ethanol, aromatic hydrocarbons such as toluene, and aliphatic alcohols such as ethyl acetate. Ether hydrocarbons such as ester and tedrahydric lanthanum, organic chlorine hydrocarbons such as dichloromethane, dimethylformamide, dimethylsulfoxide, acetate Examples include nitrile, water and mixtures thereof. Preferable examples include aliphatic lower alcohols, aromatic hydrocarbons, ether hydrocarbons, water, and mixtures thereof.

 The reaction temperature is usually from −20 ° C. to the reflux temperature of the solvent, preferably from 0 ° C. to the reflux temperature of the solvent. This reaction can also be carried out without a solvent.

Bases to which alkali metal hydroxide of K0H and NaOH is, K ₂ CO ₃ or Na ₂ C0 ₃ for which A L'force Li metal carbonates, MeONa and EtONa and t-BuOK Alkali metal salts of aliphatic lower alcohols, such as alkali metal hydrides such as NaH, organic bases such as pyridin triethylamine, and quaternary ammonium salts such as Triton B. Preference is given to alkali metal hydroxides, alkali metal carbonates, alkali metal salts of aliphatic lower alcohols, organic bases and quaternary ammonium salts. The amount used is usually 0.001 to 10 equivalents, preferably 0.05 to 5 equivalents.

As the purification method, a commonly used method such as recrystallization, distillation, and chromatography using silica gel can be used. The general formula (4)

(Wherein X, Y, R ¹ , R ² and R ³ are the same as defined above) may be a salt thereof, for example, a sodium salt , Potassium salts, hydrochlorides, sulfates and the like. Step 2: Production of a compound of the general formula (5) from a compound of the general formula (4)

General formula (5)

(Wherein X, Y, II ¹ , ^ and R ³ represent the same as defined above).

(Wherein X, Y, II ¹ , R ² and R ³ are as defined above) or a salt thereof in a solvent in the presence or in the presence of a base or acid, or a ring thereof. Can be produced by carrying out a chemical reaction

 Solvents used in the above reaction include, for example, methanol and ethanol.

-Aliphatic lower alcohols such as toluene, aromatic hydrocarbons such as toluene, aliphatic esters such as ethyl acetate, ether hydrocarbons such as tetrahydrofuran, franc, etc. Organic chlorine-based hydrocarbons such as dimethyl ether, dimethylformamide, dimethylsulfoxide, acetonitril, water, and mixtures thereof. Preferable examples include aliphatic lower alcohols, aromatic hydrocarbons, ether hydrocarbons, water, and mixtures thereof. The reaction temperature is usually from 0 ° C to the reflux temperature of the solvent, preferably from 20 ° C to the reflux temperature of the solvent. This reaction can also be carried out without a solvent.

Is made basic, K0H and NaOH as any alkali metal hydroxide, K ₂ C0 ₃ and Na ₂ C0 ₃ as any alkali metal carbonates, MeONa and EtONa and t-BuOK of any aliphatic lower alcohols al Alkali metal hydrides such as metal salts, NaH, organic bases such as pyridine, triethylamine, porcine lysine, pyridine, quaternary ammonium such as Triton B Palladium metal salts, preferably alkali metal hydroxides, alkaline metal carbonates, alkaline metal salts of aliphatic lower alcohols, organic bases, quaternary ammonium salts It is. In addition, the amount of use is usually from 0.01 to 10 equivalents, preferably from 0.1 to 5 equivalents.

 The acid is an organic acid such as formic acid and acetic acid, an inorganic acid such as hydrochloric acid and sulfuric acid, and is preferably an organic acid. The amount used is usually from 0.01 to 10 equivalents, preferably from 0.1 to 5 equivalents.

The above bases and acids can be used as a mixture, and are preferably a mixture of an organic base and an organic acid. The mixing ratio of organic base: organic acid is 1:10 to 10: 1, preferably 1: 5. From 5: 1.

 By performing the first and second steps under the same reaction conditions, the general formula (4)

(Where X, Y, R ¹ and ^ are the same as defined above) without isolating the compound represented by the general formula (5)

(Where X, Y, R ¹ , R ² and R ³ are the same as defined above) can also be produced.

 As the purification method, a commonly used method such as recrystallization, distillation and chromatography using silica gel can be employed.

 [Synthetic route 2]

Step 1 Production of general formula (6) from compound of general formula (5)

General formula (6)

(Wherein X, Y, R ¹ , R ^{! And} R ³ are the same as defined above) are represented by the general formula (5)

(Wherein X, Y, R ¹ , and R ³ are the same as defined above) in a solvent, in the presence or absence of an inorganic salt, in the presence of a borohydride compound or hydride. It can be produced by performing a reduction reaction with a reducing agent such as an aluminum compound.

 Examples of the solvent used in the above reaction include aliphatic lower alcohols such as methanol and ethanol, aromatic hydrocarbons such as toluene, and ethers such as tetrahydrofuran. Hydrocarbons, water and mixtures thereof. Preferred are aliphatic lower alcohols, ether hydrocarbons, water and mixtures thereof.

 This reaction can also be performed without a solvent.

The reaction temperature is usually from −40 ° C. to the reflux temperature of the solvent, preferably from 120 ° C. to 40 ° C. Is an inorganic salts include etc. CeC l _3. The amount of the borohydride used is usually from 0.1 to 5 equivalents, preferably from 0.5 to 2 equivalents, such as NaBH ₄ and NaBH ₃ CN. Examples of the aluminum halide compound include LiAlH ₄ . Rather than the favored include NaBH _4. The amount of use is usually from 0.2 to 5 equivalents, preferably from 0.25 to 4 equivalents.

 The purification can be performed by a commonly used method such as recrystallization, distillation and chromatography using silica gel.

Step 2: Production of the compound of the general formula (7) from the compound of the general formula (6)

General formula (7)

Compound represented by (wherein X, Y, Z, RR ³ and Q represents those same as those defined above) is general formula (6)

(6) (Wherein X, Y, R ¹ , R ² and R ³ are the same as defined above) in a solvent in the presence or absence of a base in a solvent. The compound can be produced by reacting a logizing agent, an acylating agent, a sulfonylating agent and the like.

 Solvents used in the above reaction include, for example, aliphatic lower alcohols such as methanol, ethanol, aromatic hydrocarbons such as toluene, and aliphatic esters such as ethyl acetate. Ether-based hydrocarbons such as tel, tetrahydrofuran, chloromethane, organic chlorinated hydrocarbons such as 1,2-dichloroethane, n-hexane And aliphatic hydrocarbons, water and mixtures thereof. Preferably, aromatic hydrocarbons, aliphatic hydrocarbons, chlorinated organic hydrocarbons, and mixtures thereof are mentioned.

 The reaction temperature is usually from −30 ° C. to the reflux temperature of the solvent, preferably from 110 ° C. to the reflux temperature of the solvent. This reaction can also be carried out without a solvent.

As a base K0H and NaOH as any alkali metal hydroxide, K ₂ C0 ₃ and Na ₂ C0 ₃ for which A L'force Li metal carbonates, MeONa and EtONa and t-BuOK of any aliphatic lower alcohol over Alkali metal salts, alkali metal hydrides such as NaH, and organics such as pyridin and triethylamine Bases and the like, preferably alkali metal hydroxides, alkali metal carbonates, alkali metal salts of aliphatic lower alcohols, organic bases, and quaternary ammonium salts

 Examples of the halogenating agent include chlorinating agents such as thionyl chloride, phosgene, oxalyl chloride, oxychloride, and pentachloride; brominating agents such as thionyl bromide and oxybromide. And the like, and preferably, thionyl chloride, phosgene, and oxychlorinated phosphorus. The amount used is usually from 0.5 to 10 equivalents, preferably from 0.8 to 5 equivalents.

 Examples of the acylating agent include acetic anhydride, acetyl chloride, benzoyl chloride and the like. It is usually used in an amount of 0.5 to 10 equivalents, preferably 0.8 to 5 equivalents.

Examples of the sulfonylating agent include methansulfonyl chloride, trifluoromesulfonyl anhydride, benzenesulfonyl chloride, and p-toluenesulfonyl chloride. The amount used is usually from 0.5 to 10 equivalents, preferably from 0.8 to 5 equivalents. The general formula (6)

(6) (Where X, Y, R ¹ , Ri and R ³ are the same as defined above) from the compound represented by the general formula (8)

(Where X, Y, R ¹ , R ^s and R ³ are the same as defined above) can be produced.

 The purification can be performed by a commonly used method such as recrystallization, distillation, and chromatography using silica gel.

Step 3 Production of compound of general formula (8) from compound of general formula (7)

General formula (8)

(Wherein X, Y, R ¹ , R ² and R ³ are the same as defined above) are represented by the general formula (7)

(Wherein X, Ys Q, R ¹ , ^ and R ³ are the same as defined above) by treating the compound with a base in a solvent. Can be manufactured.

 Examples of the solvent used in the above reaction include aliphatic lower alcohols such as methanol, ethanol, aromatic hydrocarbons such as toluene, and aliphatic esters such as ethyl acetate. Organic hydrocarbons such as tetrahydrofuran, dichloromethan, etc., organic solvents such as dichloromethan, dimethylformamide, dimethylsulfoxide, and acetone. Examples include tonitrile, water and mixtures thereof. Preferable examples include aliphatic lower alcohols, aromatic hydrocarbons, ether hydrocarbons, water, and mixtures thereof.

 The reaction temperature is usually from 120 ° C to the reflux temperature of the solvent, and preferably from 110 ° C to the reflux temperature of the solvent. This reaction can also be carried out without a solvent.

Examples of the base include alkali metal hydroxides such as K 0 H and NaOH, K ₂ C0 ₃ and Na ₂ C0 ₃ as any alkali metal carbonates, MeONa and EtONa and t-BuOK of any aliphatic lower alcohols al force Li metal salts, NaH for any alkali metal hydride, Pi Li Jinya Organic bases such as triethylamine and DBU, and quaternary ammonium salts such as Triton B, preferably alkali metal hydroxides, alkali metal carbonates, and aliphatic lower alcohol alcohols It is a lithium salt. The amount used is usually from 0.5 to 10 equivalents, preferably from 0.8 to 5 equivalents.

 As a purification method, it can be purified by a commonly used method such as recrystallization, distillation, and chromatography using a silica gel.

Fourth step: production of a compound of the general formula (9) from a compound of the general formula (8)

General formula (9)

(Wherein X, Y, R ¹ , and R ³ are the same as those defined above) are represented by the general formula (8)

(Wherein X, Y, R ¹ , and R ³ are the same as defined above) can be produced by performing a dehydrogenation reaction in a solvent. it can.

 Examples of the solvent used in the above reaction include aliphatic alcohols such as methanol, aromatic hydrocarbons such as toluene, ethyl acetate and methyl benzoate, and the like. Ether-based hydrocarbons such as aliphatic and aromatic esters and tetrahydrofuran diglyme, and organic chlorinated carbons such as dichloromethane and 1,2-dichloroethane. Aliphatic hydrocarbons such as hydrogen, n-hexane, organic acids such as acetic acid, aliphatic and aromatic nitriles such as acetonitrile and phenylnitrile, water, and mixtures thereof Is mentioned. Preference is given to aromatic hydrocarbons, ether hydrocarbons, aliphatic hydrocarbons, organochlorine hydrocarbons, aliphatic and aromatic nitriles, organic acids, water and mixtures thereof.

The reaction temperature is usually from room temperature to 400 ° C., preferably from 50 ° C. to 300 ° C. This reaction can also be performed without a solvent. Is an oxidizing agent KMn0 _4, Mn0 _2, metal oxides such as CrO _2, platinum Roh La di um, male Mi um, Lee Li di um, alone or a salt of ruthenium and b Jiu arm of any platinum group element And halogenating agents such as thionyl chloride and sulfuryl chloride; quinone derivatives such as DDQ; sulfur; and oxygen. Examples of the salts of platinum group elements include mineral salts such as hydrochlorides. Platinum group elements alone or their salts such as hydrochloric acid are activated carbon, graphite, silica, alumina, silica-alumina, zeolite, titania, magnesia, zirconia, silica. It may be in the form of an appropriate simple substance such as soil or barium sulfate. The amount used is usually from 0.001 to 20 equivalents, preferably from 0.05 to 10 equivalents.

 These oxidation reactions can be performed in the presence of oxygen. As the purification method, a commonly used method such as recrystallization, distillation and chromatography using a silica gel can be employed.

 [Synthetic route 3]

The first step can be performed in the same manner as the first step of the synthesis route 2. Second step: Production of the compound of the general formula (10) from the compound of the general formula (6) General formula (10)

(Wherein X, Y, R ¹ and R ³ are the same as defined above) are represented by the general formula (6)

(Wherein X, Y, R ¹ , and R ³ are the same as defined above) in a solvent or without solvent in the presence of a dehydrating agent. It can be manufactured more.

Solvents used in the above reaction include, for example, aliphatic lower alcohols such as methanol and ethanol, aromatic hydrocarbons such as toluene, tetrahydrofuran and the like. Examples include ether hydrocarbons, dichloromethane, 1,2-organochlorine hydrocarbons such as dichloroethane, n-hexacyclic aliphatic hydrocarbons such as hexane, water, and mixtures thereof. Can be Preferably aliphatic lower alcohols, aromatic hydrocarbons, aliphatic hydrocarbons, organochlorine hydrocarbons, water and their And mixtures thereof.

 The reaction temperature is usually between 120 ° C. and 400 ° C., and is preferably

The temperature is from 0 ° C to 300 ° C, and the solvent reflux temperature when a solvent is used. Dehydrating agents include inorganic acids such as hydrochloric acid, sulfuric acid, and boric acid, acidic salts such as potassium hydrogen sulfate, salts such as iron sulfate, toluene sulfonic acid, methansulfonate, and the like. Examples thereof include sulfonic acids, alumina, silica gel, and mixtures thereof. Is rather to good or sulfate, bisulfate mosquito Li U beam, etc. _{F e S 0 4 · S i} 0 a ₂ like et be. In addition, the usage amount is usually from 0.01 to 10 equivalents, preferably from 0.1 to 10 equivalents.

5 equivalents.

 Also, halogenating agents such as thionyl chloride, oxylin chloride, and boron tribromide, sulfonating agents such as p-toluenesulfonyl chloride, methanesulfonyl chloride, and acetyl chloride Alternatively, an esterifying agent such as pyridine and triethylamine can be reacted in the presence of a base such as pyrimidine or triethylamine for dehydration. The amount used is usually from 0.5 to 10 equivalents, preferably from 0.8 to 5 equivalents.

As the purification method, a commonly used method such as recrystallization, distillation, and chromatography using silica gel can be used. Step 3 From the compound of the general formula (10) to the compound of the general formula (9) Manufacturing of

General formula (9)

(Wherein X, Y, R ¹ , and R ³ are the same as defined above) are represented by the general formula (10)

(Where X, Y, R ¹ , R ² and R ³ are the same as defined above) are produced by performing a dehydrogenation reaction in a solvent. be able to.

Examples of the solvent used in the above reaction include aliphatic alcohols such as methanol and ethanol, aromatic hydrocarbons such as toluene methene, ethyl acetate and methyl benzoate. Any aliphatic and aromatic esters, ether hydrocarbons such as tetrahydrofuran diglyme, and organic chlorinated carbons such as dichloromethane and 1,2-dichloroethane. Aliphatic hydrocarbons such as hydrogen, η-hexane, organic acids such as acetic acid, and acetonitrile vinyl nitrite And aliphatic and aromatic nitriles such as water, water and mixtures thereof. Preference is given to aromatic hydrocarbons, ether hydrocarbons, aliphatic hydrocarbons, organochlorine hydrocarbons, aliphatic and aromatic nitriles, organic acids, water and mixtures thereof.

The reaction temperature is usually from room temperature to 400 ° C, preferably from 50 ° C to 300 ° C. This reaction can also be performed without a solvent. Is an oxidizing agent _{KMn0 4, Mn0 2, C rO} 2 of any metal oxides, platinum Bruno La indium, male Mi um, Lee Li indium, alone, or a salt thereof Rireteniumu and b Jiu arm of which platinum group elements, Examples include thionyl chloride, a nodulating agent such as sulfuryl chloride, quinone derivatives such as DDQ, sulfur, oxygen, and the like. Examples of salts of platinum group elements include mineral salts such as hydrochlorides. Platinum group elements alone or their salts such as hydrochloric acid are activated carbon, graphite, silica, alumina, silica-alumina, zeolite, titania, magnesia, zirconia, It may be in the form of an appropriate single substance such as diatomaceous earth or barium sulfate. The amount used is usually from 0.001 to 20 equivalents, preferably from 0.05 to 10 equivalents.

These oxidation reactions can be performed in the presence of oxygen. The purification method used was recrystallization, distillation, silica gel, etc. Can be purified by commonly used methods such as chromatography.

 [Synthetic route 4]

Step 1 Production of a compound of the general formula (11A) and / or (11B) from a compound of the general formula (5)

General formula (11A) and / or (11B)

(Wherein X, Y, W, RR ^j and R ³ represent the above.) Is a compound represented by the general formula (5)

Can be produced by reacting the compound represented by with a halogenating agent in a solvent.

Examples of the solvent used in the above reaction include aromatic hydrocarbons such as toluene, aliphatic esters such as ethyl acetate, ether hydrocarbons such as tetrahydrofuran, and dichloromethane. Such Organic hydrocarbons, aliphatic hydrocarbons such as n-hexane, and mixtures thereof. Preference is given to aromatic hydrocarbons, organochlorine hydrocarbons, aliphatic hydrocarbons and mixtures thereof. This reaction can also be carried out without a solvent.

 The reaction temperature is usually from 120 ° C to the reflux temperature of the solvent, and preferably from 0 ° C to the reflux temperature of the solvent.

 Examples of the halogenating agent include chlorinating agents such as thionyl chloride, phosgene, oxalyl chloride, oxychloride, and pentachloride; brominating agents such as thionyl bromide and oxybromide. And oxalyl chloride, phosgene and oxychlorinated phosphorus. The amount used is usually from 0.5 to 10 equivalents, preferably from 0.8 to 5 equivalents.

 An amide compound such as dimethylformamide can be added for the purpose of accelerating the reaction and improving the yield, and the amount of the amide compound used is usually 0.01 to 5 equivalents. And preferably from 0.05 to 3 equivalents.

In addition, in some cases, isomers derived from the difference in the position of the double bond are present in this reaction, but the ratio may be any. These isomers are usually used for chromatography such as chromatography using silica gel. It is possible to divide according to the method used, but even in the state of a mixture, there is no effect on the next step.

 As the purification method, a commonly used method such as recrystallization, distillation and chromatography using silica gel can be used. Second step: General formula (11A) and / or Or production of a compound of general formula (9) from a compound of (11B)

General formula (9)

(Wherein X, Y, R ¹ , R ² and R ³ are the same as defined above) are represented by the general formula (11A) and / or

(1 1 Β)

(Wherein X, Y, W, R ¹ , and R ³ are the same as defined above) by treating the compound with a base in a solvent or without a solvent. Can be manufactured. Examples of the solvent used in the above reaction include aliphatic lower alcohols such as methanol and ethanol, aromatic hydrocarbons such as toluene, and tetrahydrofuran. Examples include ether hydrocarbons such as lan, organic hydrocarbons such as dichloromethane, dimethylformamide, dimethyl sulfoxide, water, and mixtures thereof. Preferable examples include aliphatic lower alcohols, aromatic hydrocarbons, ether hydrocarbons, water, and mixtures thereof.

 The reaction temperature is usually from 120 ° C. to the reflux temperature of the solvent, and preferably from 0 ° C. to the reflux temperature of the solvent.

Is made basic, K0H, NaOH of which alkali metal _{hydroxide, K 2 C0 3, Na 2} C0 3 of which Anore force Li metal carbonates, MeONa, EtONa, t-BuOK of any aliphatic lower alcohol over Organic bases, such as alkali metal hydrides, alkali metal hydrides such as NaH, pyridines and triethylamines, preferably alkali metal hydroxides, alkali metal carbonates Salts are alkali metal salts of aliphatic lower alcohols. The amount used is usually 0.5 to 10 equivalents, preferably 1 to 5 equivalents.

[Synthetic route 5] The first step can be performed in the same manner as the first step of the synthesis route 4. Second step: From the compound of the general formula (11A) and / or (11B), the general formula (12 ))

General formula (1 2)

(Wherein X, Y, W, R ¹ , R ′ and R ³ are the same as defined above) are represented by the general formula (11A) and / or (1 1 B)

(1 1 B)

(Wherein X, Y, W, R ¹ and R ³ are the same as defined above) are produced by performing a dehydrogenation reaction in a solvent. be able to

 Examples of the solvent used in the above reaction include, for example, methanol and ethanol.

—Aromatic alcohols such as toluene, aromatics such as toluene Hydrocarbons, aliphatic and aromatic esters such as ethyl acetate and methyl benzoate, ether hydrocarbons such as tetrahydrofuran di-glyme, dichloromethan Chlorinated organic hydrocarbons such as 1,2-dichlorobenzene, aliphatic hydrocarbons such as n-hexane, organic acids such as acetic acid, and acetonitril and phenylni. Aliphatic and aromatic ditolyls such as tolyl, water and mixtures thereof. Preference is given to aromatic hydrocarbons, ether hydrocarbons, aliphatic hydrocarbons, organochlorine hydrocarbons, aliphatic and aromatic nitriles, organic acids, water and mixtures thereof. .

The reaction temperature is usually from room temperature to 400 ° C, and preferably from 50 ° C to 300 ° C. This reaction can also be carried out without a solvent. _{KMn 0 4, Mn 0 2,} C r O 2 of which the metal oxide is an oxidizing agent, a platinum - Bruno La di U beam, the male actual sales arm, Lee Li di c arm, Rireteni © arm and ii di © Metal salts such as metal or its salts, thionyl chloride, halogenating agents such as sulfuryl chloride, quinone derivatives such as DDQ, sulfur, oxygen, etc. Is Examples of the salts of platinum group elements include mineral salts such as hydrochlorides. Platinum group elements alone or their salts such as hydrochloric acid are activated carbon, graphite, silica, alumina, silica-alumina, zeolite, titania, and magnesium. Gunsia, Zirconia, It may be in the form of a suitable simple substance such as diatomaceous earth or barium sulfate. The amount used is usually from 0.001 to 20 equivalents, preferably from 0.05 to 10 equivalents.

 These oxidation reactions can be performed in the presence of oxygen. The purification can be performed by a commonly used method such as recrystallization, distillation, and chromatography using silica gel.

Third step: Production of the compound of the general formula (9) from the compound of the general formula (12)

General formula (9)

(Wherein X, Y, R ¹ and R ³ are the same as defined above) are represented by the general formula (12)

(Where X, Y, W, R ¹ , and R ³ are the same as defined above. Can be produced by performing a dehalogenation reaction in a solvent in the presence of hydrogen and a catalyst.

 Examples of the solvent used in the above reaction include aliphatic lower alcohols such as methanol, ethanol, and the like, aliphatic esters such as ethyl acetate, aromatic hydrocarbons such as toluene, and tetane. Examples include ether-based hydrocarbons such as lanthanum-furan, organic acids such as acetic acid, water, and mixtures thereof. Preferable examples include aliphatic lower alcohols, aliphatic esters, ether hydrocarbons, organic acids, water and mixtures thereof. This reaction can also be performed without a solvent.

 The reaction temperature is usually from 0 ° C to the reflux temperature of the solvent, and preferably from room temperature to the reflux temperature of the solvent.

Examples of the catalyst include a simple substance of a platinum group element such as platinum, palladium and rhodium or a salt thereof. Examples of salts of platinum group elements include mineral salts such as hydrochlorides. Platinum group elements alone or their salts can be activated carbon, graphite, silica, alumina, silica-alumina, zeolite, titania, magnesia, zirconia, silicon dioxide. It may be in the form of an appropriate simple substance such as soil or barium sulfate. Its usage is usually between 0.001 and 20 equivalents. And preferably from 0.05 to 10 equivalents.

The hydrogen pressure is from normal pressure to 10 kgf / cm ² , preferably from normal pressure to 5 kgf / cm ² .

Or If necessary K0H and NaOH of which Al force Li metal hydroxide, K ₂ C0 ₃ and Na ₂ C0 ₃ for which Al force Li metal carbonates, MeONa and EtONa and t-BuOK of any aliphatic lower It is also possible to add a dehydrochlorinating agent such as an organic base such as alcohol metal salt, pyridin or triethylamine.

 As the purification method, a commonly used method such as recrystallization, distillation, and chromatography using a silica gel can be employed. Example

 Hereinafter, the present invention will be described more specifically with reference to Examples.

Reference Synthesis Example 1 Preparation of 2-((4-methylphenyl) propionyl) -1-5-ethylhexyl ester

4'-Methylpentylacetic acid ethyl ester 2.28 g (11. 1 mmol) of ethanol solution (10 ml) was added to sodium methoxide 11 mg (0.16 mmo 1 ) Was added, and 2.0 g (27.8 mm01) of methyl vinylketone was slowly dropped at 25 ° C or less under cooling. The mixture was stirred at the same temperature for 4 hours. Ethanol under reduced pressure After distillation, the mixture was acidified by adding diluted hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with a saturated saline solution and dried over anhydrous magnesium sulfate. Next, anhydrous magnesium sulfate was filtered, and the solvent was distilled off under reduced pressure to obtain a residue. This was purified by silica gel chromatography chromatography (hexyl monoacetate) to obtain the target substance as pale yellow oil. (2.73 g, yield

8 9.0%)

HNMR (ppm, 3 0 0 MH z, CDC 1 3)

δ 79 2 (2 H, d, J = 8.0 Hz)

 7 2 8 (2H, d, J = 8.0Hz)

 4 4 1 (H t J = 70Hz)

 4.14 (2H, q, J = 6.9Hz)

 2.5 5 to 2.60 (2H, m)

 2.42 (3 H, s)

 2.2 0 to 2.2 5 (2 H, m)

 2.1 3 (3 H, s)

 1.17 (3H, t, J = 6.9Hz)

Reference Synthesis Example 2 2-((4-Methylphenyl) carbonyl)

5 — Manufacture of oxohexannitrile 4-Methylpenzoylacetonitrile 1.0 g (6.29 mm 01) of toluene solution (20 ml) is added to 1.0 ml (1 ml) of methylvinylketone. 2.6 mmol) and 0.088 ml (0.63 mm01) of triethylamine were added, and the mixture was stirred at room temperature for 24 hours. The solvent was distilled off under reduced pressure, and the resulting residue was removed. The product was purified by silica gel chromatography chromatography (ethyl hexyl monoacetate), and the target product was obtained as pale yellow oil. (1.0 g, 69.4% yield)

^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

ό "795 (2H, d, J = 8.0Hz)

 3 3 (2 H, d, J = 8.0 Hz)

 4 6 4 (1 H, d d, J = 95.1 .1 H z)

 7 8 to 2.89 (2H)

 2.4.4 (3H, s)

 2.30 to 2.40 (1H, m)

 2.2 1 (3 H, s)

 2.0 3 to 2.16 (1H, m)

Reference Synthesis Example 3 2 — (4-Methyl phenyl) 1-4 —Oxosic Mouth Hexyl — 2 —Ethylene Carbonate

2 — ((4-Methyl phenyl) carbonyl) 1-5 — To a solution of ethyl acetate (4.19 g, 15.2 mmol) in toluene (10 ml) was added 137 mg of acetic acid (2.28 mmo 1) and pyridine 12. 9 mg (l.52 mmol) was added, and the mixture was heated at 110 ° C for 9 hours. After cooling to room temperature, ethyl acetate was added, and the mixture was washed with dilute hydrochloric acid and saturated saline. The organic layer was dried over anhydrous magnesium sulfate, then filtered, and the solvent was distilled off under reduced pressure to obtain a residue. This was purified by silica gel chromatography chromatography (ethyl hexane monoacetate) and the target substance was obtained as brown oil. (3.46 g, 88.0% yield)

¹ H-NMR (Dpm, 300 MHz, CDC

δ 7 4 1 (2 Η, d, J = 8.2 Η)

 2 1 (2 Η, d, J = 8.2 Η)

 4 7 (1 Η, s)

 4 1 1 (2 Η q J = 7 0 Η ζ)

 3.96 (1,, d d, J = 4.8, 4.8 Η)

 2.5 5 to 2.65 (1 Η, m)

 2.40 to 2.55 (3 layers)

 2. 3 8 (3Η, s)

1.14 (3Η, t, J = 7.. Η Η) Reference Synthesis Example 4 2—Fenru 4 1-year-old Kisocyclohexyl 1-2—Production of ethyl ester of carboxylic acid

 2 In a toluene solution (5 ml) of 3.87 g (14.8 mmol) of phenylhexanol-5-oxohexanoate was added 130 mg of acetic acid (2 ml). . 17 mm 01) and 127 mg (1.49 mmo 1) of pyridin were added, and heated at 110 ° C for 5 hours. After cooling to room temperature, ethyl acetate was added, and the mixture was washed with dilute hydrochloric acid and saturated saline. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off under reduced pressure to obtain a residue. The product was purified by silica gel chromatography chromatography (hexyl monoacetate) to obtain the target product as a brown oil. (4.02 g, 94.7% yield)

^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

δ7.50 (2H, d, J = 3.0, 6.4Hz)

 7.40 to 7.48 (3H)

 6.47 (1 H, s)

 4.1 1 1 (2H, q, J = 7.0Hz)

 3.96 (1H, dd, J = 3.7, 3.7Hz)

2.6 to 2.70 (1H, m) 2.35 to 2.55 (3H)

 1.1 2 (3H, t, J = 7.0Hz)

Reference Synthesis Example 54 4-Chloro-2-phenylphenylhexaethyl, 41-Jethylcarboxylate and 41-Chloro-2-ethylphenylcyclohexaneー 1, 3 — Manufacture of a mixture of ethyl carbene ester

 2 — Phenyl 4-oxocyclohexyl 2 — Ethyl ester of encarponic acid 1.24 g (5.1 lmmol) of a toluene solution (10 ml) ) Was added to 2.58 mg (20.4 mmo 1) of oxalyl chloride, and the mixture was heated and stirred at 70 to 75 ° C for 2 hours. Next, the mixture was cooled to room temperature, ethyl acetate was added, and the mixture was washed sequentially with water, a saturated aqueous sodium hydrogen carbonate solution, and a saturated saline solution. The organic layer was dried over magnesium sulfate anhydride, filtered, and the solvent was distilled off under reduced pressure to obtain the target substance as a pale yellow oil. (1.24 g, yield 93.0%)

^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

δ 7.25 to 7.45 (8 Η)

 7.13 to 7.16 (2 layers)

6.35 ί 1 ί, s) 6 1 9 (1 H, s)

 5 8 7 (1H, brs)

 4.09 (2 H q J = 73 H z)

 9 3 (2 H, q, J = 7.3 H z)

 3.64 (1H, dd, J = 3.3, 8.6Hz)

 2 90 0 to 3.05 (1H, m)

 60-2.85 (5H)

 3 4 (3 H J = 7 3 H z)

 0 8 9 (3H, t, J = 7.3Hz)

Example 1 Production of ethyl acetyl acetate

 Ethyl acetate (4.0 m 1, 41.3 mmol) was obtained in a toluene solution (100 ml) of ethyl isonicotinate (5.0 g, 33.l mmol). t _ B u OK (5.6 g,

49.6 mm ο 1) was gradually added. After stirring at room temperature for 4 hours, water was added to the reaction solution, and further neutralized with 5% hydrochloric acid. The organic layer was separated, washed with water and saturated saline, and then dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained crystals were washed with hexane to give the desired product as pale brown crystals. (1.0 g, 15.7%) HNMR (ppm, 3 0 0 MH z, CDC 1 3)

 6 1 2 .4 4 (1 H, s)

 7 2 (2 H, d, J = 5.6 H z)

 7.6 2 (2H, d, J = 5.6Hz)

 7 7 (H s)

 4 3 0 (2 H, q, J = 7.1 H z)

 1.3 5 (3 H, t, J = 7.1 H z)

Example 22 Preparation of 2-isonicotinyl-5-oxohexanoic acid ethyl ester

 To a solution of isonicotinyl acetate ethyl ester (1.0 g, 18 mmol) in ethanol (5 ml) was added (sodium methoxide (35 mg, 0.5 mg). 18 mmo 1) was added, and methyl bilketone (400 mg, 5.70 mmol) was slowly dropped under ice-cooling. After the temperature was gradually raised to room temperature, the mixture was stirred overnight. After ethanol was distilled off under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated saline solution and dried with anhydrous magnesium sulfate.

The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel chromatography (ethyl hexane monoacetate), and the desired product was obtained as pale yellow oil. . (978 mg, yield 71.8%) ^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

δ 8 8 3 (2 H, t, J = 1 a n d 4.8 Hz)

 8 1 (2 H, t, J = 18 a n d 4.8 H z)

4 4 0 (1 H, d d, J = 6 4 a n d 7.0 H z)

4 1 5 (2H, q, J = 6.9Hz)

 60 to 2.70 (2H, m)

 4 to 2.35 (2H, m)

 5 (3 H, s)

 1 7 (3 H, t, J = 6.9 H z)

Example 3 2-(4-pyridyl) 1 4 1 year old

2 — Manufacture of enethyl ester

 Acetic acid (137 mg) was added to a toluene solution (20 ml) of 2-isonicotinol-5-oxohexanoate (978 mg, 15.2 mmol). , 5.57 mmo 1) and pyridin (31 1 mg, 3.66 mm ο 1) were added, and the mixture was dehydrated under reflux with heating.

After the completion of the reaction, the reaction solution was cooled to room temperature, and ethyl acetate was added thereto, followed by washing with water and saturated saline. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. Get The residue obtained is collected by silica gel chromatography chromatography (hexane).

—Ethyl acetate) to give the desired product as a brown oil. ( Five

(23 mg, yield 57.4%)

H - NMR (ppm, 3 0 0 MH z, CDC 1 3)

δ 8 6 8 (2 H, d d, J = 1 an d 4.8 Hz)

 3 5 (2 H, d d, J = an d 4.8 .8 H z)

5 0 (1 H, s)

 4 2 (2 H, q, J = 6.9 H z)

 9 1 (1 H, t, J = 4.6 H z)

 2.3 5 7 5 (4H, m)

 1.63 (3H, t, J = 6.9Hz)

Example 4 Preparation of 4—Hydroxy 2— (4-Pyridine) cyclohexyl 2—Ethylene Carbonate

2 — (4 — pyridyl) 1-4-oxocyclohexyl 2 — Enthanol ester methyl ester (523 mg, 2.13 mm 01) To the solution (5 ml) was added sodium borohydride (81.0 mg, 2.13 mmol) little by little at 0 ° C, and the mixture was stirred at the same temperature for 1 hour. did. After evaporating the solvent under reduced pressure, water was added to the residue, and the mixture was extracted with ethyl acetate. Water and saturated diet After successive washing with brine, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue is purified by silica gel chromatography (ethyl hexane monoacetate) to give the desired product as white crystals (melting point: 89 to 90 ° C). ). (366011, yield 68.4%)

1 H - NMR (ppm, 3 0 0 MH z, CDC 1 3)

δ 8.5 4 (2H, d, J = 5.8Hz)

 7.2 0-7.2 .2 6 (2 H, m)

 6.40-6.36 (1H, dandd, J = 2.9and4.4Hz)

 4.3 3-4.5 3 (1 H, br)

 4.00-4.10 (2H, m)

 3.6 9 an d 3.6 1 (1 H, t an d t, J = 5.8 an d 5.2 Hz)

 1.70-2.30 (4H, m)

 1.09 (3 H, m)

Example 5 Preparation of 4—Cro-guchi 2— (4—Pyridyl) cyclohexyl 2-Ethylene Carbonyl Ethyl Ester

4 — Hydroxy 1 — (4 — pyridyl) cyclohexyl 2 — Ethyl encarponic acid ester (360 mg, 1.46 mm 01) was dissolved in a mixed solvent of dichloromethane (3 ml) and toluene (3 ml), and the mixture was dissolved in ice-cooled titanium chloride. Nil (0.265 ml 3.64 mm 01) was added. Added Komizu stirring for 1 hour at room temperature, was neutralized with saturated N a HC 0 ₃ water are al and hand extracted acetate Echiruesu ether. The organic layer was washed successively with water and a saturated saline solution, dried over magnesium sulfate anhydride, and the solvent was distilled off to obtain 41-chloro-2- (4-pyridyl) silicone. Ethyl ester of chlorohexyl-2-ene-carbonate was obtained as a colorless oil. (3 9 0 mg, 1 0 0%) 1 H - NMR (ppm, 3 0 0 MH z, CDC 1 3)

δ 8.5 5-8.60 (2 H, m)

 7.2 5 — 7.2 7 (2 H, m)

 6.4 a then d 6.3 4 (1 H, d an d d, J = 4.6 a d 3.9 H z)

 4.8.5 and 4.7.4 (1H, m)

 4.05 (2H, q, J = 7.0Hz)

 3.6 0-3.7 5 (1 H, m)

 2.05-2.41 (4H, m)

1.1 1 and 1. 0 3 (3 H, tandt, J = 7.0 and 6.9 Hz)

Example 6 Production of 2- (4-pyridyl) cyclohexane 1,3—Jenethyl Ester Carbonate

 Tert-butanol 4- (2-pyridyl) cyclohexyl 2- (2-ethylene carbonate) (390 mg, 1.46 mm 01) Then, tret-Bu0K (246 mg, 2.19 mmo 1) was added to the solution under water cooling. After stirring at room temperature for 1 hour, the solvent was distilled off, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue is purified by silica gel chromatography chromatography (ethyl hexane monoacetate), and then purified to 2_ (4—pyridyl) cyclo. The 1,3-diene carboxylate ester was obtained as a pale yellow oil. (2 12 mg, 63.5%)

^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

 6 8.5. 6 (2 H, t, J = l. 9 an d 4.8 H z)

7.09 (2 H, t, J = l. 9 an d 4.8 Hz)

6.1 5 — 6.2 4 (1 H, m)

5.97 (1H, dt, J = l. 8 and 9.8Hz) 3.96 (2 HQJ = 7.0 Hz)

 5 7-2.6.7 (2 H, m)

 2 8-2.38 (2 H, m)

 0 9 4 (3H, t, J = 7.0Hz)

Example 7 Production of 4- (2-ethoxypropylonylphenyl) pyridine

2- (4-Pyridyl) cyclohexa-1,3-diethyl carboxylate (100 mg, 0.437 mmo 1) was added to acetic acid (1.5 m). It was dissolved in a mixed solution of 1) and water (1.5 ml), 5% Pd / C (30 mg) was added, and the mixture was heated under reflux for 2 hours. After cooling, the catalyst was filtered off, made alkaline with dilute NaOH water, and extracted with ethyl acetate. After the organic layer was washed with a saturated saline solution, the solvent was distilled off. After adding toluene to the residue, the residue was dried with magnesium sulfate anhydride and dried with magnesium sulfate anhydride. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel chromatography chromatograph (hexyl monoacetate) to give 4-(2 1-1) A mixture of (ethoxycarbonyl) phenyl) pyridine and 2— (4—pyridyl) cyclohexyl 2—encarponic acid ethyl ester Obtained as a colorless oil. The formation ratio was about 2: 1 (86.5 mg, 87.2%)

 4 One (2-ethoxycarbonylphenyl) pyridin

¹ H-NMR (ppm, 300 MHz, CDC

δ 8 6 3 (binary, t, J = l. 6 an d 4.9 Hz)

7 9 4 (1 H, d d, J = l. 4 a d d 7 H z)

5 47.62 (1H, m)

 4 6-7.5. 3 (1 H, m)

 3 3 (1 H, d d, J = 1.3 a n d 7.1 Hz)

2 4 (2 H, t, J = 1.6 a n d 4.9 Hz)

4 1 2 (2 H, d, J = 7.0 Hz)

 1.04 (3H, t, J = 7.0Hz)

 (4 — pyridyl) cyclohexyl 2 — encarponic acid ester

δ 8 5 3 (binary, d d, J = l. 5 an d 4.9 Hz)

7.06 (2 H, d d, J = l. 5 an d 4.9 Hz)

3.90 (2H, d, J = 7.2Hz)

 2.40-2.50 (2H, m)

 2.3 0-2 '. 4 0 (2 H, m)

1.7 0 — 1.8 3 (4 H, m) 0.88 (3H, t, J = 7.2Hz)

Example 8 4—Hydroxy 2—Phenyl Cyclohex 2—Preparation of Enethyl Ester

 4—Oxo-1—Phenylcyclohexyl-2-—Ethyl ester of encarboxylate (500 mg, 2.05 mmol) in methanol (10 ml) Was added at 0 ° C to the mixture at 0 ° C, and the mixture was stirred at the same temperature for 45 minutes. . After adding 5% HCI water, the solvent was distilled off under reduced pressure, water was added to the residue, and the mixture was extracted with ethyl acetate. After successive washing with water and saturated saline, the organic layer is dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. 4-Hydroxy-12-phenylcyclohexyl-2-ene carboxylate was obtained as pale yellow crystals. (504 mg, yield 100%)

1 H - NMR (ppm, 3 0 0 MH z, CDC 1 3)

δ 7.2 3 — 7.3 4 (5H, m)

 6.1 0 — 6.2 2 (1 H, m)

 4.30-4.50 (1 H, m)

3.90-4.08 (2H, m) 3.7 2 and 3.6 4 (1 H, tandt, J = 5.8 and 5.3 H z)

 1.6 0-2.3 0 (4 H, m)

 1 .0 0 a n d 1 .1 0 (3 H, m)

Example 9 Preparation of 41-chloro-2—phenylcyclohexyl-2—ethyl ester of carboxylic acid

4—Hydroxy-2—phenylcyclohexyl-2-eneethyl ester (100 mg, 0.407 mmol) was dissolved in toluene (2 ml). At 5 ° C., thionyl chloride (0.074 ml, 1.02 mm 01) was added. After stirring at room temperature for 3 hours, water was added, and the mixture was extracted with ethyl acetate. Saturated organic layer N a HC 0 ₃ was washed sequentially with water and with brine, the solvent was distilled off and dried over anhydrous sulfate Ma Gune shea © beam, 4 one click B B - 2 - off et two Hexyl hex-2-ethyl ester was obtained as a pale yellow oil. (Ll O mg, 100%)

1 H - NMR (ppm, 3 0 0 MH z, CDC 1 3)

67.25-7.3.7 (5H, m)

6.2 7 and 6.1.8 (1H, dandt, J = 4.6 and 1.7Hz) 4.8 7-4.7.9 1 and 4.74-4.79 (lH, m) 4.03 and 3.96 (2H, q, J = 6.9 and 7.1H z)

 3.6 8-3.7.6 (l H, m)

 2.05-2.3.3 7 (4H, m)

 1.09 a n d 0.9.7 (3 H, t, J = 6.9 an d 7.1 Hz)

Example 10 Preparation of 1,2-phenylcyclohexa 1,3—ethyl ethyl ester

4 1-Cross mouth 1 _ 2 -phenylcyclohexyl 2 — Ethyl ester of encarponic acid (110 mg, 0.407 mmol) was added to tert-butanol (2 ml). ), And added with potassium tert-butoxide (93 mg, 0.832 mm01) under water cooling. After stirring at room temperature for 1 hour, water was added, the mixture was acidified with 5% aqueous HC1, and extracted with ethyl acetate. The organic layer is washed with a saturated saline solution, dried over anhydrous magnesium sulfate, and the solvent is distilled off to remove 2-, phenylcyclohexane-1,3, -ethyl carboxylate. The ester was obtained as a pale yellow oil. (70 mg, 74%) ¹ H-NMR (ppm, 300 MHz, CDC

 6 7 1 4-7.3.3 9 (5 H, m)

 0 3-6.2.4 (2H, m)

 3.9 4 (2 H q J = 6.9 H z)

 2.5 5-2.6.5 (2 H, m)

 2.26-2.3.5 (2H, m)

 9 0 (3 H, t, J = 6.9 H z)

Example 1 1 2 — Preparation of biphenyl alcohol ester

2 — Phenylcyclohexa 1, 3 — Ethylene sterile dicarboxylate (90 mg, 0.395 mmol) was added to acetic acid (1.5 ml) and water (1.5 ml). ), 5% Pd / C (50 mg) was added, and the mixture was heated under reflux for 2 hours. After cooling, the catalyst was removed by filtration and the solvent was distilled off. Toluene was added to the residue, and the mixture was dried over magnesium sulfate anhydride, and the solvent was distilled off to obtain 2-ethylphenyl ethyl carboxylate as a pale yellow oil. (7 1 mg

80%)

^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

6 7.8 2 (1 H, dd, J = l. 4 and 7.7 H z) 7.1 0-7.0.6 (8 H)

 4.08 (2H, d, J = 7.0Hz)

 0.98 (3 H, t, J = 7.0 Hz)

Example 1 2 4 —Chloro 2 —phenyl cyclohexaene 2, 41 Ethyl carboxylate ester and 41 —Cro mouth 1 2 —Phenyl cyclohexa 1 1, 3 — Preparation of a mixture of ethyl carbene esters

 2 — Phenol 4 — Oxocyclohexyl 2 — Ethyl ester of encarboxylate 1.2 4 g (5.1 lmmol) of a toluene solution (10 ml) ) Was added with 2.58 mg (20.4 mmo 1) of oxalyl chloride, and the mixture was heated and stirred at 70 to 75 ° C for 2 hours. Then, the mixture was cooled to room temperature, ethyl acetate was added, and the mixture was washed with water, a saturated aqueous solution of sodium hydrogencarbonate, and a saturated saline solution in that order. The organic layer was dried over magnesium sulfate anhydride, then filtered, and the solvent was distilled off under reduced pressure to obtain the target substance as a pale yellow oil. (1.24 g, yield 93.0%)

^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

δ 7.2 5 to 7.4 5 (8 Η) 7 1 3 to 7.16 (2H)

 3 5 (1 H, s)

 1 9 (1 H, s)

 8 7 (1 H, b r s)

 4.09 (2 H q J 7.3 H z)

 3.93 (2 H q J = 73 H z)

 3 6 4 (1 H, d d, J = 3.3, 8.6 H z)

 90-3.05 (1H, m)

 6 0 2 .8 5 (5 H)

 1.3 4 (3 H, t, J = 7.3 H z)

 0.89 (3H, t, J = 7.3Hz)

Example 13 Preparation of 3 4 -Chloro 2 -Biphenyl Carponic Acid Ester and 4 -Chloro 2 -Biphenyl Carboxylic Acid

4-chloro-2—phenylcyclohexane 1,2-diethyl-potassium rubonic acid ester and 4-chloro-2—phenylcyclohexene-1,3-dicarboxylic acid A mixture of ethyl esters (200 mg, 0.762 mmol) was dissolved in tert-butanol (3 ml), and the mixture was dissolved at 5 ° C in potassium tert-butoxide (10%). 3 mg, 0.9 mm0 1) was added, and the mixture was stirred at room temperature for 2 days. Water was added to the reaction solution, the mixture was acidified with 5% aqueous HC1 and extracted with ethyl acetate. The organic layer is washed with a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent is distilled off to obtain 41-chloro-2-ethylphenyl ester and ethyl ester. A mixture of 41-biphenyl-2-carboxylic acid was obtained as a pale yellow oil (200 mg).

 4 — Chlorine 2 — Biphenyl alcohol

1 H - NMR (ppm, 3 0 0 MH z, CDC 1 3)

δ 7.79 (1H, d, J = 8.0Hz)

 7.1 0-7.5 0 (7 H)

 4.07 (2H, d, J = 6.9Hz)

 0.98 (3H, t, J = 6.9Hz)

4 One black 2 — Biphenyl alcohol

1 H - NMR (ppm, 3 0 0 MH z, CDC 1 3)

δ 7.9 1 (1H, d, J = 8.7Hz)

Example 14 Production of 2-bis-ethyl carboxylate and 2-biphenyl carboxylic acid

4-Krollo 2-biphenyl ethyl carboxylate and 4 Dissolve a mixture of 2-hydroxybenzoic acid (200 mg) in ethanol (10 ml) and add 5% Pd / C (200 mg). The mixture was stirred at room temperature under a hydrogen stream at a pressure of 3 kgf / cm ² for 2 days. The catalyst was removed by filtration, and the solvent was distilled off to obtain a mixture of 2-ethylphenylcarboxylate and 2-biphenylcarboxylic acid.

 2 — biphenyl carboxylic acid ethyl ester

^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

 6 7.8 2 (1 H, d d, J = l. 4 an d 7.7 H z)

7.10 — 7.60 (8H)

 4.08 (2H, d, J = 7.0Hz)

 0.98 (3 H, t, J = 7.0 Hz)

2 — Bif enilcarponic acid

^{1 H - NMR (ppm, 3} 0 0 MH z, CDC 1 3)

δ7.95 (1H, d, J = 7.9Hz)

Industrial applicability

According to the present invention, an aromatic ring-substituted benzene derivative that is useful as an intermediate for pharmaceuticals and agrochemicals, liquid crystals, heat-resistant polymers, liquid crystalline polymers, etc. can be efficiently produced. This synthesis method uses inexpensive raw materials and special It is an industrial method for the efficient production of aromatic-substituted benzene derivatives without the need for reaction conditions.

Claims

The scope of the claims

1. General formula (1)

 X

0 ^Y (1)

[Wherein X is at least one of Ν, 0, and S and is a 5- or 6-membered optionally substituted heterocyclic ring or an optionally substituted heterocyclic ring and benzene. Condensate (provided that the number of substituents is 1 to 3 and may be the same or different and may be substituted, Η, 0Η, or substituted (\ to ( ₆ alkyl groups, substituted Optionally substituted C ₂ -C ₆ alkenyl group, optionally substituted C ₂ -C ₆ alkynyl group optionally substituted (^-( ₆ alkoxy group, optionally substituted alkylthio group , NR ⁴ R ^5, Nono ^{_{androgenic, N0 2, CN, COR 6}} , C0 2 R 6, CONR 4 R 5 S0 3 R 6, S0 2 NR 4 R 5, S0R 6, S0 2 R 6, 0C0R 6, 0C0 ^{_{2 R 6, 0C0NR 4 R 5}} , 0S0 2 R 6, optionally substituted phenylpropyl group, optionally substituted full et Bruno alkoxy group, but it may also be substituted A teloaryl group or a substituted or unsubstituted heteroaryl group; and a 4- to 7-membered ring may be formed by an adjacent substituent. ), Y indicates C0 ₂ R ⁶ , CN, NO S0 ₃ R ⁶ , S 0 ₂ NR ⁴ R ⁵ , SOR ⁶ , SO ₂ R ⁶ , R ⁴ , R ⁵ and R ⁶ are H, substituted Sa (^ Represents an alkyl group of ₆ to ₆ or an optionally substituted phenyl group, and R ⁴ and R ⁵ may form a 4- to 7-membered ring.] A ketone derivative represented by the general formula (2)

[Wherein R ^1, R2 and R ³ is H, ~ optionally substituted C _e of § alkyl group, optionally substituted C ₂ -C ₆ alkenyl group, may be substituted C ₂ to C ₆ alkynyl group, which may be substituted (^ to (^ alkoxy group, optionally substituted alkylthio group, NR ⁴ R halogenogen NO CN ヽ C0R C0 ₉ R ⁶

_{^{C0NR 4 R 5, S0 3 R}} 6, S0 2 NR 4 R 5, SOR 6, S0 2 R 6, OCOR 6, 0C0 2 R 6, 0C0NR 4 R 5, 0S0 2 R 6, optionally substituted off An enyl group, an optionally substituted phenoxy group, an optionally substituted heteroaryl group, or an optionally substituted heteroaryloxy group; R ⁴ , R ⁵ and R ⁶ shows the above. ] To the general formula

( Four )

[Wherein X, Y, R ¹ , Ri and R ³ represent the above. A general formula characterized by synthesizing a compound represented by the formula

( Five )

[Wherein X, Y, R ¹ , and R ³ represent the above. Method for producing a hexahexone derivative represented by

 General formula (1)

 X

 , 丫

 0 '(1)

[Wherein X and Y are the same as those defined in claim 1]. ] And the general formula (3)

[Wherein R ¹ R ^; and R ³ represent the same as defined in claim 1, and Z represents a leaving group. ] To react with the general formula (4)

[Wherein X, Y, R ¹ , and R ³ are the same as defined in claim 1]. Wherein a compound represented by the general formula (5) is synthesized and then subjected to a cyclization reaction.

[Wherein X, Y, R ¹ , and R ³ are the same as defined in claim 1]. For producing cyclohexenone derivatives represented by

3. General formula (5)

[Wherein X, Y, R ¹ , R ^; and R ³ are the same as defined in claim 1]. ] To the cyclohexenone derivative represented by the general formula (6)

[Where X, Y, R ¹ , Ri and R ³ are the same as those defined in claim 1] Show the same thing. Cyclohexenol derivative represented by the general formula (7) by introducing a leaving group in the presence or absence of a base.

[Wherein X, Y, R ^1, and R ³ indicates those same as those defined in claim 1, Q is Nono _{^{androgenic, 0C0R 7, 0C0 2 R 7}} , 0C0NR 4 R 5 or 0s0 ₂ the R ⁷ indicates, R ⁷ is shows the optionally substituted (~ ₍₆ alkyl group or an optionally substituted off Eniru group, also R ⁴ and R ⁵ are as defined in claim 1, After conversion to a cyclohexene derivative represented by the formula [1], a elimination reaction is carried out in the presence of a base to obtain a compound of the general formula (8)

[Wherein X, Y, R ¹ , ^ and R ³ represent the same as defined in claim 1]. A cyclohexadiene derivative represented by the general formula (9):

[Wherein X, Y, R ¹ and R ³ are the same as defined in claim 1]. A method for producing a heterocyclic-substituted benzene derivative represented by the formula:

4 General formula (6)

 [Wherein X is an optionally substituted benzene, naphthylene ring, N,

A 5-membered or 6-membered ring having at least one of 0 and S, an optionally substituted heterocyclic ring or a condensed product thereof with benzene (optionally substituted) However, the number of substituents is 1 to 3, which may be the same or different, H, 0H, C which may be substituted.

A C ₆ -C ₆ alkyl group, an optionally substituted C ₂ -C ₆ alkenyl group, and an optionally substituted C. -C ₆ alkynyl group, substituted or unsubstituted Ci-C ₆ alkoxy group, optionally substituted alkylthio group, NR ⁴ R ⁵ , nitrogen, N 0 ₂ , CN, COR ⁶ _N C 0 ₂ R ⁶ , _{^{C0NR 4 R 5, S0 3 R}} 6, S0 2 NR 4 R 5, SOU 6, S0 2 R 6, 0C0R 6, 0C0 2 R 6, 0C0NR 4 R 5, 0S0 2 R 6, optionally substituted off Represents an enyl group, an optionally substituted phenoxy group, an optionally substituted heteroaryl group or an optionally substituted heteroaryloxy group, and further adjacent to each other And a 4- to 7-membered ring may be formed depending on the substituent), and Y, R ¹ s Ri and are the same as defined in claim 1. In the presence of a base, or in the absence of a base, a leaving group is introduced into the cyclohexenol derivative represented by the general formula (7)

[Wherein X, Y, R ¹ , ^ and R ³ represent the above, and Q represents the same as defined in claim 3]. Is converted to a cyclohexene derivative represented by the general formula (8) by performing an elimination reaction in the presence of a base.

[Wherein X, Y, RR ′ and are as defined above. ] Represented by] A general formula (9) characterized in that after the mouth hexadiene derivative is synthesized, a dehydrogenation reaction is further performed.

[Wherein X, Y, II ¹ , and R ³ represent the above. ] A method for producing an aromatic ring-substituted benzene derivative represented by the formula:

General formula (5)

[Wherein X, Y, R ¹ and R ³ are the same as defined in claim 1]. ] To the cyclohexenone derivative represented by the general formula (6)

[Wherein X, Y, R ¹ , R ² and R ³ represent the same as defined in claim 1]. Cyclohexenol derivative represented by Further, by further performing a dehydration reaction, the general formula (10)

Wherein X, Y, R ¹ , ^ and R ³ are the same as defined in claim 1. A general formula characterized by performing a dehydrogenation reaction after conversion to a cyclohexadiene derivative represented by the formula (9):

[Wherein X, Y, R ¹ , and R ³ are the same as defined in claim 1]. Of heterocyclic-substituted benzene derivatives represented by

General formula (5)

[Wherein X, Y _s R ^1, and show those same as those defined in claim 1. The cyclohexenone derivative represented by (11A) and Z or (11B)

[Wherein, X, Y, R ¹ , and R ³ represent the same as defined in claim ¹ , and W represents halogen. Wherein the halogen derivative represented by the general formula (9) is synthesized, and further subjected to a dehydrohalogenation reaction.

[Wherein X, Y, R ¹ , and R ³ are the same as defined in claim 1]. A method for producing a heterocyclic-substituted benzene derivative represented by the formula:

7 General formula (5)

[Where X, Y, R and R ³ are the same as defined in claim 1] Show the same thing. The cyclohexenone derivative represented by the formula (11A) and / or (11B) is reacted with a halogenating agent.

[In the formula, X, Y, R ¹ , Ri and R ³ represent the same as defined in claim 1, and W represents the same as defined in claim 6. By synthesizing a halogen derivative represented by the general formula (12)

[Wherein, X, Y, R ¹ , and R ³ represent the same as defined in claim ¹ , and W represents the above. Wherein the heterocyclic-substituted benzene derivative represented by the general formula (9) is synthesized and then subjected to a dehalogenation reaction.

[Wherein X, Y, R ¹ , R ² and R ³ are the same as defined in claim 1] Indicates the one. Of heterocyclic-substituted benzene derivatives represented by

8. General formula (11 A) and / or (11 B)

[Wherein ^{_{X, Y s W, R 1}} , Ri and R ³ indicates the ones same also to that defined in claim 4, W and those Ji also bet same as defined in claim 6 Show. ] To the halogen derivative represented by the general formula (12)

[Wherein X, Y, W, R ¹ , R ² and R ³ represent the above. A heterocyclic-substituted halobenzene derivative represented by the general formula (9), which is further subjected to a dehalogenation reaction.

(9) [Wherein, X, Y, R ¹ , and represent the same as defined in claim 4]. ] A method for producing an aromatic ring-substituted benzene derivative represented by the formula:

9. General formula (5)

(Wherein X, Y, R ¹ , and R ³ are the same as defined in claim 1).

1 0 General formula (6)

(Wherein X, Y, R ¹ , Ri and R ³ are the same as defined in claim 1). Cyclohexenol derivative represented by the formula:

1 1. General formula (7)

(Where X, Y, R ¹ , and R ³ represent the same as defined in claim 4 and Q represents the same as defined in claim 3). Rohexenone derivative

1 2 General formula (8)

(Wherein X, Y, R ¹ , Ri and R ³ are the same as defined in claim 4).

13 General formula (10)

(Wherein X, Y, R ¹ , and R ³ are the same as defined in claim 1).

14. General formula (11A) and / or (11B)

(11B) (Wherein X, Y, R ¹ , R ′ and R ³ represent the same as defined in claim 1, and W represents the same as defined in claim 6). Nodrocycline represented Hexadiene derivative

1 5. — General formula (9)

(Wherein X, Y, R and R ³ are the same as defined in claim 4).

16 General formula (1 2)

(Where X, Y, RR ² and R ³ represent the same as defined in claim 4, and W represents the same as defined in claim 6). Aromatic ring-substituted halobenzene derivatives.