WO2016141563A1 - 脂环式环氧化合物及其制造方法、以及2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法 - Google Patents

脂环式环氧化合物及其制造方法、以及2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法 Download PDF

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WO2016141563A1
WO2016141563A1 PCT/CN2015/073991 CN2015073991W WO2016141563A1 WO 2016141563 A1 WO2016141563 A1 WO 2016141563A1 CN 2015073991 W CN2015073991 W CN 2015073991W WO 2016141563 A1 WO2016141563 A1 WO 2016141563A1
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formula
halogen atom
atom
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大野充
张雷涛
刘冰
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Daicel Corp
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Daicel Corp
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Priority to CN201580072340.8A priority patent/CN107207457A/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/04—Compounds containing oxirane rings containing only hydrogen and carbon atoms in addition to the ring oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/78—Halides of sulfonic acids
    • C07C309/85—Halides of sulfonic acids having halosulfonyl groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
    • C07D327/04—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
    • C07D497/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D497/18—Bridged systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the present invention relates to a novel alicyclic epoxy compound useful as a raw material for synthesizing a 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]decane derivative and a process for producing the same
  • the 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]decane derivative can be used as a raw material for coatings, functional polymers, medicines, pesticides and other fines. Raw materials for chemicals.
  • the present invention relates to a process for producing a 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]nonane derivative using the above alicyclic epoxy compound as a raw material.
  • a method for producing a decane derivative for example, after hydrolyzing a sulfonyl halide derivative, treatment with an oxidizing agent to obtain 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 A method of 3,7 ]decane derivative (see Patent Document 2).
  • Patent Document 1 Japanese Laid-Open Patent Publication No. 2007-31355
  • Patent Document 2 Japanese Patent No. 5352387
  • Patent Document 2 when pyridine is used as the base for hydrolysis, the above continuous yield is up to 47%, but in the case of using the pyridine, the pyridine is Since it is carried out in the form of a sulfonate as an oxidation step in a subsequent step, there is a risk that the explosive pyridine N-oxide is produced as a by-product, and industrial implementation is difficult.
  • Another object of the present invention is to provide a process for producing a 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]nonane derivative which can be industrially carried out safely and efficiently.
  • the present inventors have found that a newly discovered alicyclic epoxy compound (2,3-epoxybicyclo[2.2.1]heptane-2-ene-5-sulfonyl halide derivative) can be utilized as a raw material.
  • An industrially safe and effective process yields the desired 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]nonane derivative, thereby completing the present invention.
  • the present invention relates to the following scheme.
  • R 1 , R 2 , R 3 and R 4 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a halogen atom, or an optional hydroxyl group protected by a protecting group; Further, a hydroxyalkyl group having 1 to 6 carbon atoms which has a halogen atom is optional.
  • R 5 , R 6 and R 7 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a halogen atom, a carboxyl group which may form a salt, a substituted oxycarbonyl group, or the like.
  • a sulfinyl group of a salt a substituted oxysulfinyl group, a sulfo group optionally forming a salt, a substituted oxysulfonyl group, or a cyano group.
  • Q represents a methylene group, an oxygen atom or a sulfur atom which may be optionally substituted by one or two alkyl groups having 1 to 3 carbon atoms.
  • n represents 1 or 2.
  • X represents a halogen atom.
  • R 1 , R 2 , R 3 and R 4 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a halogen atom, or an optional hydroxyl group protected by a protecting group; Further, a hydroxyalkyl group having 1 to 6 carbon atoms which has a halogen atom is optional.
  • R 5 , R 6 and R 7 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a halogen atom, a carboxyl group which may form a salt, a substituted oxycarbonyl group, or the like.
  • a sulfinyl group of a salt a substituted oxysulfinyl group, a sulfo group optionally forming a salt, a substituted oxysulfonyl group, or a cyano group.
  • Q represents a methylene group, an oxygen atom or a sulfur atom which may be optionally substituted by one or two alkyl groups having 1 to 3 carbon atoms.
  • n represents 1 or 2.
  • X represents a halogen atom.
  • the method comprises treating an alicyclic olefin compound represented by the following formula (2) with an oxidizing agent to produce an alicyclic epoxy compound represented by the above formula (1).
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q, n and X have the same meanings as in the formula (1).
  • the spatial position of R 1 and R 2 and the spatial position of R 7 and S(O) n X are respectively selected to be inward or outward.
  • R 1 , R 2 , R 3 and R 4 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a halogen atom, or an optional hydroxyl group protected by a protecting group; Further, a hydroxyalkyl group having 1 to 6 carbon atoms which has a halogen atom is optional.
  • R 5 , R 6 and R 7 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a halogen atom, a carboxyl group which may form a salt, a substituted oxycarbonyl group, or the like.
  • a sulfinyl group of a salt a substituted oxysulfinyl group, a sulfo group optionally forming a salt, a substituted oxysulfonyl group, or a cyano group.
  • Q represents a methylene group, an oxygen atom or a sulfur atom which may be optionally substituted by one or two alkyl groups having 1 to 3 carbon atoms.
  • n represents 1 or 2. The spatial position of R 1 and the hydroxyl group is optionally inward or outward.
  • the method comprises:
  • the alicyclic epoxy compound represented by the following formula (1) is hydrolyzed to obtain a compound represented by the following formula (3), and a cyclization reaction is carried out to produce a 2-hydroxy group represented by the above formula (4).
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q and n have the same meanings as in the formula (4).
  • X represents a halogen atom.
  • the spatial positions of R 1 , R 2 and the epoxy group, and the spatial positions of R 7 and S(O) n X groups are optionally inward or outward.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q and n have the same meanings as in the formula (4).
  • M represents a hydrogen atom, an alkali metal, an alkaline earth metal, or a quaternary ammonium group.
  • the spatial position of R 1 , R 2 and the epoxy group, and the spatial position of R 7 and the S(O) n OM group are optionally inward or outward.
  • 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]decane can be produced by an industrially safe and effective method. Things.
  • 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]decane derivative obtained by this method as a raw material, 4-oxo-5-thiatricyclo can be obtained.
  • a decane derivative for example, a derivative having a polymerizable group, etc. which can be hydrolyzed while maintaining stability such as chemical resistance when derivatized into a polymer or the like
  • the solubility in water and the solubility in water is a compound which is useful as a monomer component such as a highly functional polymer.
  • Fig. 1 is a chart of the 1 H-NMR spectrum of the compound represented by the formula (iia) obtained in Example 1.
  • Example 2 is a spectrum of a 1 H-NMR spectrum of a compound represented by the formula (2a) obtained in Example 1 (in the case of using dichloromethane as a reaction solvent).
  • Example 3 is a spectrum of a 1 H-NMR spectrum of a compound represented by the formula (2a) obtained in Example 1 (in the case of using acetonitrile as a reaction solvent).
  • Example 4 is a spectrum of a 1 H-NMR spectrum of a compound represented by the formula (1a) obtained in Example 1 (in the case of using hydrogen peroxide as an oxidizing agent).
  • Fig. 5 is a chart showing the 1 H-NMR spectrum of the compound represented by the formula (1a) obtained in Example 1 (when m-chloroperbenzoic acid was used as an oxidizing agent).
  • Fig. 6 is a chart showing the 1 H-NMR spectrum of the compound represented by the formula (4a) obtained in Example 1.
  • the alicyclic epoxy compound of the present invention is a compound represented by the following formula (1) (an alicyclic epoxy compound having a sulfonyl halide or a sulfinyl halide moiety).
  • R 1 , R 2 , R 3 and R 4 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a halogen atom, or an optional hydroxyl group (hydroxyl group).
  • R 5 , R 6 and R 7 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a halogen atom, a carboxyl group which may optionally form a salt, and a substituted oxygen.
  • Q represents a methylene group, an oxygen atom or a sulfur atom which may be optionally substituted by one or two alkyl groups having 1 to 3 carbon atoms.
  • n represents 1 or 2.
  • the halogen atom may, for example, be a fluorine atom, a chlorine atom or a bromine atom.
  • the alkyl group having 1 to 6 carbon atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a t-butyl group, a pentyl group, and a hexyl group.
  • an alkyl group having 1 to 3 carbon atoms is preferable, and a methyl group is more preferable.
  • alkyl group having 1 to 6 carbon atoms having a halogen atom examples include a chloroalkyl group such as a chloromethyl group; a fluorine such as a trifluoromethyl group, a 2,2,2-trifluoroethyl group or a pentafluoroethyl group; An alkyl group (preferably a fluoroalkyl group having 1 to 3 carbon atoms) or the like.
  • Examples of the hydroxyalkyl group having 1 to 6 carbon atoms include a hydroxymethyl group, a 2-hydroxyethyl group, a 1-hydroxyethyl group, a 3-hydroxypropyl group, a 2-hydroxypropyl group, and a 4-hydroxybutyl group. 6-hydroxyhexyl and the like.
  • Examples of the hydroxyalkyl group having 1 to 6 carbon atoms having a halogen atom include difluorohydroxymethyl, 1,1-difluoro-2-hydroxyethyl, and 2,2-difluoro-2-hydroxyethyl. Base, 1,1,2,2-tetrafluoro-2-hydroxyethyl and the like.
  • hydroxyalkyl groups having 1 to 6 carbon atoms having a halogen atom a hydroxyalkyl group having a carbon number of 1 or 2 (particularly, 1 carbon atom) or a hydroxyhaloalkyl group is preferable.
  • the protective group of the hydroxyl group of the hydroxyalkyl group having 1 to 6 carbon atoms which has a halogen atom may, for example, be a protective group which is generally used as a protective group of a hydroxyl group in the field of organic synthesis, for example, methyl group, methoxy group.
  • a group such as a group which can form an ether or an acetal bond together with an oxygen atom constituting a hydroxyl group; a group such as an acetyl group or a benzoyl group which can form an ester bond with an oxygen atom constituting a hydroxyl group.
  • the salt of a carboxyl group, a sulfinyl group, and a sulfo group include an alkali metal salt, an alkaline earth metal salt, and a transition metal salt.
  • the substituted oxycarbonyl group may, for example, be an alkoxycarbonyl group such as a methoxycarbonyl group, an ethoxycarbonyl group, an isopropyloxycarbonyl group or a propoxycarbonyl group (C 1-4 alkoxy-carbonyl group); An oxycarbonyl group such as a vinyloxycarbonyl group or an allyloxycarbonyl group (such as a C 2-4 alkenyloxy-carbonyl group); a cycloalkyloxycarbonyl group such as a cyclohexyloxycarbonyl group; and an aryloxycarbonyl group such as a phenoxycarbonyl group; Wait.
  • an alkoxycarbonyl group such as a methoxycarbonyl group, an ethoxycarbonyl group, an isopropyloxycarbonyl group or a propoxycarbonyl group (C 1-4 alkoxy-carbonyl group);
  • An oxycarbonyl group such as
  • the substituted oxysulfinyl group or the substituted oxysulfonyl group may, for example, be a substituted oxysulfinyl group or a substituted oxysulfonyl group corresponding to the above substituted oxycarbonyl group.
  • examples of the alkyl group having 1 to 3 carbon atoms which are optionally substituted on the methylene group include a methyl group, an ethyl group, a propyl group and the like.
  • the methylene group substituted by one or two alkyl groups having 1 to 3 carbon atoms may, for example, be a methylmethylene group or a dimethylmethylene group.
  • R 1 , R 2 , R 3 and R 4 which are the same or different, preferably represent a hydrogen atom; an alkyl group having 1 to 3 carbon atoms such as a methyl group or a trifluoromethyl group; or a halogenated alkyl group; the hydroxy group is optionally protected
  • the hydroxyalkyl group having a carbon number of 1 to 3 or a hydroxyhaloalkyl group is more preferably a hydrogen atom.
  • R 5 , R 6 and R 7 which are the same or different, preferably represent a hydrogen atom; an alkyl group having 1 to 3 carbon atoms such as a methyl group or a trifluoromethyl group or a halogenated alkyl group (particularly methyl group, halogenated group A). a substituted oxycarbonyl group; a cyano group, more preferably a hydrogen atom. Further, as n, it is preferably 2, and as Q, a methylene group is preferable.
  • X represents a halogen atom.
  • the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom.
  • the spatial position of R 1 , R 2 and the epoxy group in the formula (1) is optionally inward or outward. Further, the spatial position of R 7 and the S(O) n X group in the formula (1) is optionally inward or outward.
  • Representative examples of the compound represented by the formula (1) include a compound represented by the following formula (including each stereoisomer).
  • X and n each have the same meanings as in the formula (1).
  • Ac represents an acetyl group.
  • the method for producing the alicyclic epoxy compound of the present invention is not particularly limited.
  • the compound represented by the following formula (2) (alicyclic olefin compound) can be treated with an oxidizing agent to form the alicyclic ring of the present invention.
  • Epoxy compound alicyclic olefin compound
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q, n and X have the same meanings as in the formula (1), respectively (in the formula (1) R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q, n and X correspond).
  • the spatial positions of R 1 and R 2 and the spatial positions of R 7 and S(O) n X groups are optionally inward or outward.
  • the compound represented by the formula (2) can be produced by a known or customary method, and is not particularly limited, for example,
  • the compound represented by the following formula (ii) (unsaturated sulfonyl halide or unsaturated sulfinyl halide) and the compound represented by the following formula (iii) (cyclopentadiene derivative) can be obtained as follows.
  • a furan derivative or a thiophene derivative is produced by a Diels-Alder reaction.
  • R 5, R 6 , R 7, the same meaning as n, and X, respectively of formula (1) in the (respectively of formula (1) R 5, R 6, R 7 , n and X-phase correspond).
  • R 1 , R 2 , R 3 , R 4 and Q in the formula (iii) have the same meanings as in the formula (1) (respectively with R 1 , R 2 , R 3 , R in the formula (1), respectively. 4 and Q correspond).
  • Examples of the compound represented by the formula (ii) include vinylsulfonic acid, ⁇ -methylvinylsulfonic acid, ⁇ -methylvinylsulfonic acid, ⁇ -trifluoromethylvinylsulfonic acid, and ⁇ -.
  • a halide of an unsaturated sulfonic acid such as trifluoromethylvinylsulfonic acid, ⁇ -cyanovinylsulfonic acid, ⁇ -cyanovinylsulfonic acid, ⁇ -carboxyvinylsulfonic acid or ⁇ -carboxyvinylsulfonic acid a halide of an unsaturated sulfinic acid or the like corresponding to these compounds.
  • Examples of the compound represented by the formula (iii) include 1,3-cyclopentadiene, 1-methyl-1,3-cyclopentadiene, and 2-methyl-1,3-cyclopentadiene. , 5-methyl-1,3-cyclopentadiene, 1,2-dimethyl-1,3-cyclopentadiene, 1,4-dimethyl-1,3-cyclopentadiene, 2 ,3-dimethyl-1,3-cyclopentadiene, 1,2,3,4-tetramethyl-1,3-cyclopentadiene, 1,2,3,4,5-pentamethyl -1,3-cyclopentadiene, 1-hydroxymethyl-1,3-cyclopentadiene, 1,4-bis(hydroxymethyl)-1,3-cyclopentadiene, 2,3-dual (hydroxymethyl)-1,3-cyclopentadiene, 1-acetoxymethyl-1,3-cyclopentadiene, 1,4-bis(acetoxymethyl)-1,3-ring a cyclopentadiene derivative such
  • the reaction of the compound represented by the formula (ii) with the compound represented by the formula (iii) can be carried out in the presence or absence of a solvent.
  • a solvent include an ester such as ethyl acetate; an organic acid such as acetic acid; an alcohol such as t-butanol; a halogenated hydrocarbon such as chloroform, dichloromethane or 1,2-dichloroethane; and an aromatic hydrocarbon such as benzene; Alkane, An aliphatic hydrocarbon such as heptane or octane; an alicyclic hydrocarbon such as cyclohexane; an amide such as N,N-dimethylformamide or N,N-dimethylacetamide; acetonitrile, propionitrile, benzonitrile, etc. Nitrile; chain or cyclic ether such as diethyl ether or tetrahydrofuran (THF).
  • the solvent may be used singly or
  • a Lewis acid may be added to the system in order to increase the reaction rate and the selectivity (stereoselectivity) of the reaction.
  • the Lewis acid is not particularly limited, and examples thereof include AlCl 3 , SnCl 4 , TiCl 4 , BF 3 , and ZnI 2 .
  • the temperature (reaction temperature) for carrying out the above reaction can be appropriately selected depending on the type of the reaction raw material and the like, and is not particularly limited, but is preferably -80 to 300 ° C, and more preferably -70 to 250 ° C. Usually, the above reaction is carried out under normal pressure or under pressure.
  • the above reaction can be carried out in any of a batch type, a semi-batch type, a continuous type, and the like.
  • the compound represented by the formula (2) produced by the above reaction can be carried out by, for example, a separation method such as filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography, or a separation method by a combination of these methods. Isolation and Purification.
  • the compound represented by the above formula (ii) can be produced by a known or customary method, and is not particularly limited.
  • the dehydrohalogenation reaction of the compound represented by the following formula (i) can be carried out as follows. To manufacture.
  • R 5, R 6 , R 7, the same meaning as n, and X, respectively of formula (1) in the (respectively of formula (1) R 5, R 6, R 7 , n and X-phase correspond).
  • Y in the formula (i) represents a halogen atom, and examples thereof include a chlorine atom, a bromine atom, and an iodine atom.
  • the above reaction dehydrohalogenation reaction
  • the oxidizing agent (the oxidizing agent used for treating the compound represented by the formula (2)) which reacts with the compound represented by the formula (2)
  • a known or customary oxidizing agent can be used, and it is not particularly limited, and examples thereof include a peroxide. (especially hydrogen peroxide) or peracid (particularly a peracid derived from hydrogen peroxide, for example, an equilibrium peracid using hydrogen peroxide described later).
  • the peroxide include a salt of hydrogen peroxide, a peroxide, a hydroperoxide, a peroxyacid, and a peroxyacid.
  • the hydrogen peroxide pure hydrogen peroxide may be used.
  • a suitable solvent for example, water
  • a suitable solvent for example, water
  • a suitable solvent for example, water
  • a suitable solvent for example, water
  • the amount of the peroxide used in the reaction is not particularly limited, and is preferably 0.9 to 5 based on 1 mol of the compound represented by the formula (2).
  • the molar ratio is more preferably 0.9 to 3 moles, still more preferably 0.95 to 2 moles.
  • peracid examples include organic peracids such as performic acid, peracetic acid, perpropionic acid, trifluoroperacetic acid, perbenzoic acid, m-chloroperbenzoic acid, and monoperoxyphthalic acid; and inorganic acids such as permanganic acid. Over acid and so on. Peracid can also be used in the form of a salt.
  • the organic peracid may also be an equilibrium peracid (eg, equilibrium percarboxylic acid, equilibrium peracetic acid, etc.). That is, for example, an organic acid such as formic acid or acetic acid may be used in combination with hydrogen peroxide to form a corresponding organic peracid in the system.
  • the amount of the peracid used in the reaction is not particularly limited, and is preferably 0.8 to 2 mol, more preferably 1 mol, per mol of the compound represented by the formula (2). It is 0.9 to 1.5 moles, more preferably 0.95 to 1.2 moles.
  • the above hydrogen peroxide is often used in combination with a metal compound.
  • the metal compound include an oxide containing a metal element such as W, Mo, V, Mn, and Re, an oxo acid or a salt thereof, a sulfide, a halide, an oxyhalide, a boride, a carbide, and a silicidation.
  • the oxide examples include tungsten oxide (WO 2 and WO 3 ), molybdenum oxide (such as MoO 2 and MoO 3 ), and vanadium oxide (VO, V 2 O 3 , VO 2 , V 2 O 5 , etc.).
  • MoO 2 and MoO 3 molybdenum oxide
  • VO vanadium oxide
  • a composite oxide containing a metal element such as W, Mo, V, or Mn.
  • oxoacid examples include, in addition to, for example, tungstic acid, molybdic acid, vanadic acid, manganic acid, and the like: polytungstic acid, homopolymolybdic acid, polyoxovanic acid equivalent polyacid; phosphotungstic acid, silicon tungsten
  • polytungstic acid homopolymolybdic acid, polyoxovanic acid equivalent polyacid
  • phosphotungstic acid silicon tungsten
  • phosphorus or silicon is preferable, and phosphorus is more preferable.
  • the oxoacid-containing salt examples include an alkali metal salt such as a sodium salt or a potassium salt of the above oxo acid; an alkaline earth metal salt such as a magnesium salt, a calcium salt or a barium salt; an ammonium salt; and a transition metal salt.
  • the salt of an oxyacid (for example, a salt of a heteropolyacid) may be a salt obtained by replacing a part of a hydrogen atom corresponding to a cation with another cation.
  • peroxide containing a metal element examples include peroxyacids such as peroxytungstic acid, peroxomolybdic acid, and peroxovanic acid; alkali metal salts, alkaline earth metal salts, ammonium salts, and transition metals of the above peroxyacids.
  • a salt of a peroxyacid such as a salt
  • a peracid such as permanganic acid
  • a salt of a peracid such as a transition metal salt.
  • the amount of the metal compound to be used in combination with the above-mentioned hydrogen peroxide is not particularly limited, but is preferably 0.0001 to 2 mol, more preferably 0.0005 to 0.5 mol, still more preferably 0.001 to 1 mol of the compound represented by the formula (2). 0.2 moles.
  • the reaction of the compound represented by the formula (2) with an oxidizing agent can be carried out in the presence or absence of a solvent.
  • a solvent a known or customary solvent can be used, and it is not particularly limited, and examples thereof include an alcohol such as t-butanol; a halogenated hydrocarbon such as chloroform, dichloromethane or 1,2-dichloroethane; and an aromatic hydrocarbon such as benzene; An aliphatic hydrocarbon such as an alkane, heptane or octane; an alicyclic hydrocarbon such as cyclohexane; an amide such as N,N-dimethylformamide or N,N-dimethylacetamide; acetonitrile, propionitrile and benzoyl Nitrile and other nitriles; chain or cyclic ethers such as diethyl ether and tetrahydrofuran; esters such as ethyl acetate; organic acids such as acetic
  • the solvent may be used singly or in combination of two or more. Further, in the case of using a solvent, the reaction may be carried out in a homogeneous system or in a heterogeneous system or a two-phase system. In the case where the reaction is carried out in a heterogeneous system, water or a solvent containing water is often used as a solvent.
  • reaction temperature at the time of reacting the compound represented by the formula (2) with the oxidizing agent can be appropriately selected in consideration of the reaction rate, the reaction selectivity, and the like, and is not particularly limited, but is preferably 0 to 100 ° C, more preferably 10 to 10 80 ° C.
  • the above reaction can be carried out in any of a batch type, a semi-batch type, a continuous type, and the like, and the same applies to the other reactions described in the present specification.
  • the carbon-carbon double bond of the compound represented by the formula (2) is epoxidized to form a compound represented by the formula (1) (the alicyclic epoxy compound of the present invention).
  • the compound represented by the formula (1) produced by the above reaction can be known, for example, by a filtration method, concentration, distillation, extraction, crystallization, recrystallization, column chromatography or the like, or a separation method obtained by combining these methods. Or a conventional purification method for separation and purification.
  • the alicyclic epoxy compound (the compound represented by the formula (1)) of the present invention can be used as a raw material for coatings, functional polymers, raw materials for medicines, agricultural chemicals, and other fine chemicals.
  • the alicyclic epoxy compound of the present invention is particularly preferably a compound represented by the following formula (4) which can be used as a raw material of a coating material, a functional polymer, a raw material of a medicine, a pesticide, and other fine chemicals ( A raw material of 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]decane derivative) is used.
  • the compound represented by the formula (4) can be produced by a method which can be carried out industrially safely and efficiently.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q and n have the same meanings as in the formula (1) (respectively with R 1 in the formula (1) , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q and n correspond). It should be noted that the spatial position of R 1 and the hydroxyl group is optionally inward or outward.
  • the production method (also referred to as "the production method of the present invention") is a method of hydrolyzing a compound represented by the formula (1) (an alicyclic epoxy compound of the present invention) to obtain a compound represented by the following formula (3). (Epider-type epoxy compound), a method of further performing a cyclization reaction to produce a compound represented by the formula (4).
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q and n have the same meanings as in the formula (1) (ie, the formula (4)) (respectively with R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Q and n in the formula (1) correspond to each other).
  • M represents a hydrogen atom, an alkali metal, an alkaline earth metal, or a quaternary ammonium group. It should be noted that the spatial positions of R 1 , R 2 and the epoxy group, and the spatial positions of R 7 and S(O) n OM groups are optionally inward or outward.
  • the alkali metal of M examples include sodium, potassium, and the like.
  • Examples of the alkaline earth metal of M include magnesium, calcium, barium, and the like.
  • the quaternary ammonium group of M may, for example, be a group formed by a cationization (for example, cationization by protonation or alkylation) of a nitrogen atom in a tertiary amine or a nitrogen-containing aromatic compound to be described later (for example, NH 4 + ; Me 3 NH + , tertiary alkyl ammonium ion such as Et 3 NH + ; pyridinium ion, etc.).
  • the method of hydrolyzing the compound represented by the formula (1) to obtain the compound represented by the formula (3) is not particularly limited, and it is possible to convert the S(O) n X group in the formula (1) into S(O) n .
  • a well-known conventional hydrolysis method for OM groups The method of hydrolysis includes, for example, a method of performing hydrolysis in the presence of an acid or a base, a method of performing hydrolysis in the absence of an acid or a base, and the like. Among them, from the viewpoint of the reaction rate and the yield, a method of performing hydrolysis in the presence of a base is preferred.
  • a known or customary base can be used, and it is not particularly limited, and examples thereof include hydroxides of alkali metals such as lithium hydroxide, sodium hydroxide, potassium hydroxide and barium hydroxide.
  • a hydroxide of an alkaline earth metal such as magnesium hydroxide, calcium hydroxide or barium hydroxide; a carbonate of an alkali metal such as lithium carbonate, sodium carbonate, potassium carbonate or cesium carbonate; a carbonate of an alkaline earth metal such as magnesium carbonate;
  • An alkali metal hydrogenate such as lithium hydrogen phosphate, sodium hydrogencarbonate, sodium hydrogencarbonate, potassium hydrogencarbonate or cesium hydrogencarbonate; an organic acid salt of an alkali metal such as lithium acetate, sodium acetate, potassium acetate or cesium acetate (for example, acetate)
  • An organic acid salt of an alkaline earth metal such as magnesium acetate (for example, acetate); an alkali metal alkoxide such as lithium methoxide, sodium methoxide, sodium ethoxide, sodium isopropoxide, potassium ethoxide or potassium t-butoxide; sodium phenolate, etc.
  • amines such as N,N-dimethylaniline, etc.; pyrrole derivatives [eg, pyrrole, N-methylpyrrole, etc.], imidazole derivatives [eg, imidazole, 1-methylimidazole, 2-methyl
  • the base may be used singly or in combination of two or more. Further, the base may be used in a form of being dissolved or dispersed in a solvent such as water.
  • the amount of the base to be used is not particularly limited, but is preferably 1 to 10 moles, more preferably 1 to 5 moles per mole of the compound represented by the formula (1).
  • a known or customary acid can be used, and it is not particularly limited, and examples thereof include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and boric acid; phosphoric acid esters; acetic acid, formic acid, and the like.
  • a carboxylic acid such as fluoroacetic acid
  • a sulfonic acid such as methanesulfonic acid, trifluoromethanesulfonic acid or p-toluenesulfonic acid
  • Such as solid acid Lewis acid such as ferric chloride.
  • the acid may be used singly or in combination of two or more.
  • the acid may be used in a form of being dissolved or dispersed in a solvent such as water.
  • the amount of the acid to be used is not particularly limited, but is preferably 1 to 10 moles, more preferably 1 to 5 moles per mole of the compound represented by the formula (1).
  • the above reaction (hydrolysis of the compound represented by the formula (1)) can be carried out in the presence or absence of a solvent.
  • a solvent a known or customary solvent can be used, and it is not particularly limited, and a solvent or the like used in the reaction of the compound represented by the above formula (2) with an oxidizing agent can be used.
  • the reaction system of the above reaction may be homogenized by mixing the organic layer and the aqueous layer, or may be a heterogeneous system or a two-phase system without mixing.
  • the substrate for example, a compound represented by the formula (1), an acid, a base or the like
  • water itself can also be used as a solvent.
  • the solvent may be used singly or in combination of two or more.
  • the amount of water used in the above reaction is not particularly limited, but is preferably from 1 to 1,000 mol, more preferably from 1 to 100 mol, per mol of the compound represented by the formula (1).
  • reaction temperature is not particularly limited, but is preferably 0 to 100 ° C, and more preferably 10 to 50 ° C.
  • time (reaction time) at which the above reaction is carried out is not particularly limited, and can be appropriately selected, for example, from the range of 0.01 to 100 hours.
  • the method of carrying out the above reaction is not particularly limited as long as it is an embodiment in which the compound represented by the formula (1) and water coexist (preferably, an embodiment in which an acid or a base (particularly a base) is further coexisted).
  • a method of adding water (for example, an aqueous solution in which an acid or a base is dissolved) to a compound represented by the formula (1) or a solution thereof, and adding the form to water (for example, an aqueous solution in which an acid or a base is dissolved) may be mentioned ( 1) A method of the compound shown or a solution thereof, and the like.
  • the compound represented by the formula (3) produced by the above reaction may be directly (without purification) supplied to the subsequent reaction (reaction of the compound represented by the formula (4)), or may be subjected to purification. Supply to subsequent reactions.
  • the purification method a known or customary method can be employed, and it is not particularly limited, and examples thereof include separation methods such as filtration, concentration, distillation, extraction, crystallization, recrystallization, and column chromatography, or a separation method obtained by combining these methods. Wait.
  • the compound represented by the formula (3) (alicyclic epoxy compound) is subjected to a cyclization reaction to produce a compound represented by the formula (4).
  • M is a hydrogen atom
  • the above cyclization reaction can be carried out, for example, simply by dissolving the compound represented by the formula (3) in a solvent.
  • M is an alkali metal, an alkaline earth metal or a quaternary ammonium group
  • the method of carrying out the above cyclization reaction may be exemplified by the presence of an acid. The method of heating as needed.
  • the acid a known or customary acid can be used, and it is not particularly limited, and examples thereof include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and boric acid; phosphates; carboxylic acids such as acetic acid, formic acid, and trifluoroacetic acid; and methanesulfonic acid; A sulfonic acid such as trifluoromethanesulfonic acid or p-toluenesulfonic acid; a solid acid such as activated clay; a Lewis acid such as ferric chloride; and the like. It is to be noted that the acid may be used singly or in combination of two or more. Further, the acid may be used in a form of being dissolved or dispersed in a solvent such as water.
  • a solvent such as water.
  • the above reaction (cyclization reaction of the compound represented by the formula (3)) can be carried out in the presence or absence of a solvent.
  • a solvent a known or customary solvent can be used, and it is not particularly limited, and a solvent or the like used in the reaction of the compound represented by the above formula (2) with an oxidizing agent can be used.
  • water itself can also be used as a solvent.
  • the solvent may be used singly or in combination of two or more.
  • reaction temperature The temperature (reaction temperature) at which the above reaction proceeds is not particularly limited, but is preferably 10 to 100 ° C, and more preferably 20 to 80 ° C.
  • time (reaction time) at which the above reaction is carried out is not particularly limited, but is preferably 1 to 40 hours, more preferably 5 to 30 hours.
  • the compound represented by the formula (4) (2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ]nonane derivative) which is produced by the above reaction can be, for example, filtered, concentrated, Separation and purification are carried out by a known or conventional purification means such as separation, distillation, extraction, crystallization, recrystallization, column chromatography or the like, or a separation method by a combination of these methods.
  • the hydrolysis reaction of the compound represented by the formula (1) and the cyclization reaction of the compound represented by the formula (3) may be carried out continuously or discontinuously.
  • the production method of the present invention may further include a step of producing a compound represented by the formula (1) (for example, a step of treating the compound represented by the above formula (2) with an oxidizing agent), or another step (for example, generating the above formula ( 2) a step of the compound shown, etc.).
  • steps and the above-described steps of performing the hydrolysis reaction and the cyclization reaction may be carried out continuously or discontinuously.
  • the compound represented by the formula (4) can be produced by an industrially safe and effective method. Specifically, the production method of the present invention does not have the risk of explosive compounds such as N-oxides which are by-produced by pyridine, such as the method described in Japanese Patent No. 5352387, which is not a compound represented by the formula (1). Further, the compound represented by the formula (4) can be produced in a high yield.
  • the compound represented by the formula (4) obtained by the production method of the present invention can be preferably used, for example, as a raw material for a coating material or a functional polymer, a raw material for medicines, agricultural chemicals, and other fine chemicals.
  • a polymerizable group for example, an acryloyl group, a methacryloyl group, or the like
  • 4-oxo-5-thiatricyclo[4.2.1.0 3,7 ] which is useful as a monomer component such as a highly functional polymer, etc., while improving the hydrolyzability and the solubility in water after hydrolysis.
  • Decane derivative The introduction of the polymerizable group into the compound represented by the formula (4) is not particularly limited, and can be carried out, for example, according to the method described in JP-A-2007-31355.
  • the compound represented by the formula (1a) was produced according to the following reaction scheme. Further, a compound represented by the formula (4a) is produced from a compound represented by the formula (1a).
  • the compound of the formula (ia) (purity: 98%, 20.00 g, 120.23 mmol) and dichloromethane (100 ml) were added to a three-necked flask containing 500 ml of a stirrer, a thermometer, and a dropping funnel, and stirred. While cooling to -5 ° C. Next, 2,6-lutidine (purity: 98%, 14.46 g, 1.1 equivalent) was dissolved in dichloromethane so that the internal temperature did not exceed 0 ° C and was added dropwise over 30 minutes. 100ml) solution. The mixture was stirred while stirring for 40 minutes while naturally warming to room temperature.
  • reaction of the step 1 can be similarly carried out by a method different from the above-described reaction scheme, specifically, when ethyl acetate is used as a solvent as described below.
  • the compound of the formula (ia) (purity: 98%, 20.00 g, 120.23 mmol) and ethyl acetate (200 ml) were added to a three-necked flask containing 500 ml of a stirrer, a thermometer, and a dropping funnel, and stirred. While cooling to -5 ° C.
  • 2,6-lutidine (purity of 98%, 14.46 g, 1.1 equivalent) was dissolved in ethyl acetate by adding it at a rate not exceeding 0 ° C and passing over 30 minutes. 100ml) solution. At this time, a white solid precipitated. The mixture was stirred while stirring for 40 minutes while naturally warming to room temperature.
  • a cyclopentadiene (3.13 g, 1.2 equivalents), phenothiazine (39 mg, 0.005 equivalent), and dichloromethane (50 ml) were placed in a three-necked flask equipped with a stirrer, a thermometer, and a dropping funnel. Cool to -10 ° C while stirring. Then, the compound represented by the formula (iia) (5.00 g, 39.51 mmol) was dissolved in dichloromethane (10 ml) by dropwise addition thereto at a rate not exceeding the internal temperature of -5 ° C over 1 hour. The resulting solution. After the completion of the dropwise addition, the resulting solution was further stirred at -10 to -5 ° C for 3 hours.
  • reaction of the step 2 can also be carried out by a method different from the above reaction scheme, specifically, when acetonitrile is used as a solvent as described below.
  • reaction of the step 3 can also be carried out by a method different from the above reaction scheme, specifically, when m-chloroperbenzoic acid (mCPBA) is used as the oxidizing agent as described below.
  • mCPBA m-chloroperbenzoic acid
  • a compound (2.00 g, 9.58 mmol) and THF (15 ml) of the formula (1a) were added to a three-necked flask equipped with a stirrer, a dropping funnel and a thermometer in a 100 ml portion. Then, a solution obtained by dissolving sodium hydrogencarbonate (2.01 g, 2.5 equivalent) in water (20 ml) was added dropwise thereto at 25 ° C for 3 minutes or more. Then, the resulting suspension was stirred at this temperature for 1.5 hours, and used in the subsequent step 5 without purification.
  • the suspension (the suspension obtained in the step 4) was stirred while stirring in a 100 ml three-necked flask equipped with a stirrer and a thermometer. Subsequently, formic acid (98%, 2.25 g, 5.0 equivalent) was added dropwise at 25 ° C for 2 minutes or more using a syringe. Then, the resulting suspension was heated to 50 ° C and stirred at this temperature for 18 hours. The THF was evaporated and the residue was diluted with ethyl acetate (100 mL).
  • the compound of the formula (4a) obtained in the steps 1 to 5 had a continuous yield of 34% based on the compound represented by the formula (ia). From this, it was confirmed that, according to the production method of the present invention, 2-hydroxy-4-oxa-5-thiatricyclo[4.2.1.0 3,7 ] can be produced in a good yield by an industrially safe and effective method. Decane derivative.
  • the compound (50 g) of the formula (ia) and dichloromethane were fed into a 500 ml three-necked flask. (150 ml), cooled to -5 °C.
  • a solution obtained by dissolving 2,6-lutidine (36.15 g) in dichloromethane (100 ml) was added dropwise thereto for 40 minutes without increasing the liquid temperature to 0 °C or higher.
  • the reaction temperature was slowly raised to 22 ° C while stirring was continued for 1.5 hours. Then, the reaction liquid was again cooled, and sulfuric acid (1%, 250 g) was added dropwise at such a rate that the liquid temperature did not exceed 10 °C.
  • reaction crude liquid A The reaction liquid thus obtained was referred to as "reaction crude liquid A". Up to this point, it corresponds to the above step 1.
  • reaction crude liquid B The reaction liquid thus obtained was referred to as "reaction crude liquid B". After the reaction crude liquid A is obtained, it corresponds to the above step 2.
  • reaction crude liquid B was kept at 5 to 10 ° C, and after adding 98% formic acid (34.57 g), a 30% aqueous hydrogen peroxide solution (41.72 g) was added dropwise over 10 minutes. After completion of the dropwise addition, the reaction was continued at a reaction temperature of 22 ° C for 40 hours. Then, the liquid temperature was cooled to 10 ° C, and a 10% aqueous sodium sulfite solution (30 ml) was added dropwise so that the liquid temperature was 10 to 15 °C. After the completion of the dropwise addition, it was confirmed by using a potassium iodide starch test paper that no peroxide remained in the system. The reaction liquid thus obtained was referred to as "reaction crude liquid C". The reaction crude liquid B is obtained up to this point and corresponds to the above step 3.
  • reaction crude liquid D An aqueous sodium hydroxide solution obtained by dissolving sodium hydroxide (47.85 g) in water (300 ml) was added dropwise to the above-mentioned reaction crude liquid C at 15 ° C for 25 minutes. After the completion of the dropwise addition, the aqueous layer and the organic layer were separated, and the organic layer was washed with water (100 ml), and the aqueous layer was separated and combined with the previous aqueous layer. The water layer thus obtained was referred to as "reaction crude liquid D". After the reaction crude liquid C is obtained, it corresponds to the above step 4.
  • the obtained organic layer was washed with water (50 g), and the organic layer was washed three times with 8% aqueous sodium hydrogen carbonate and three times with water. Then, the organic layer was concentrated, and crystallization was carried out by cooling 50 g of heptane to obtain a 2-methacryloyloxy-4-oxa-5-thiatricyclo[4.2] as a target. .1.0 3,7 ]decane-2,2-dione 4.4g.
  • the purity by gas chromatography (GC) was 99.2%, and the yield was 65%.
  • the alicyclic epoxy compound of the present invention is particularly suitably used as a raw material of a compound represented by the formula (4) which can be used as a raw material of a coating material or a functional polymer, a raw material of a pharmaceutical, a pesticide, and other fine chemicals.
  • a compound represented by the formula (4) By using the alicyclic epoxy compound of the present invention as a raw material, the compound represented by the formula (4) can be produced by a method which can be industrially carried out safely and efficiently.

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Abstract

本发明的目的在于提供作为2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的原料而有用的新型的脂环式环氧化合物。本发明的脂环式环氧化合物为下述式(1)所示的化合物。[式中，R1、R2、R3及R4相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、或任选羟基被保护基保护且任选具有卤原子的碳原子数1～6的羟基烷基。R5、R6及R7相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、任选形成盐的羧基、取代氧基羰基、任选形成盐的亚磺基、取代氧基亚磺酰基、任选形成盐的磺基、取代氧基磺酰基、或氰基。Q表示任选被1个或2个碳原子数1～3的烷基取代的亚甲基、氧原子或硫原子。n表示1或2。X表示卤原子。R1、R2与环氧基的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向。

Description

脂环式环氧化合物及其制造方法、以及2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法 技术领域
本发明涉及作为用于合成2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的原料而有用的新型的脂环式环氧化合物及其制造方法，所述2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物可被用作涂料、功能性高分子的原料、医药、农药及其它精细化学品的原料。另外，本发明涉及以上述脂环式环氧化合物为原料的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法。
背景技术
就具有聚合性基团的4-氧-5-硫杂三环[4.2.1.03，7]壬烷衍生物而言，已知其在衍生为聚合物等的情况下可以在保持耐药品性等稳定性的同时提高水解性及水解后相对于水的溶解性，是作为高功能性高分子等的单体成分等而有用的化合物(例如，参见专利文献1)。作为适宜用作4-氧-5-硫杂三环[4.2.1.03，7]壬烷衍生物的原料的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法，已公开了例如在将磺酰卤衍生物水解之后，利用氧化剂进行处理，从而得到2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的方法(参见专利文献2)。
现有技术文献
专利文献
专利文献1：日本特开2007-31355号公报
专利文献2：日本专利第5352387号
发明内容
发明要解决的问题
然而，现有技术中尚不存在工业上能够安全且有效地制造2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的方法。在专利文献2记载的方法中，例如在使用氢氧化钠作为用于水解的碱时，收率低，根据专利文献2的记载， 相对于2-氯乙烷磺酰氯的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的收率(连续收率)为29％。然而，本发明的发明人等针对上述方法进行验证时，未能获得再现性，且上述连续收率至多为7％。另一方面，根据专利文献2的记载，例如在使用吡啶类作为用于水解的碱时，上述连续收率最高可达47％，但就这样的使用吡啶类的方法而言，由于吡啶类会以磺酸盐的形式被带入作为后续工序的氧化工序，因此存在副产具有爆炸性的吡啶N-氧化物的隐患，难以实现工业上的实施。
因此，本发明的目的在于提供适宜用作2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的原料的新型的脂环式环氧化合物及其制造方法。
另外，本发明的另一目的在于提供工业上能够安全且有效地实施的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法。
解决问题的方法
本发明人等发现，通过将新发现的脂环式环氧化合物(2，3-环氧双环[2.2.1]庚烷-2-烯-5-磺酰卤衍生物)作为原料，可以利用工业上安全且有效的方法得到目标的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物，进而完成了本发明。
即，本发明涉及下述方案。
[1]下述式(1)所示的脂环式环氧化合物。
[化学式1]
Figure PCTCN2015073991-appb-000001
[式中，R1、R2、R3及R4相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、或任选羟基被保护基保护且任选具有卤原子的碳原子数1～6的羟基烷基。R5、R6及R7相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、任选形成盐的羧基、取代氧基羰基、任选形成盐的亚磺基、取代氧基亚磺酰基、任选形成盐的磺基、取代氧基磺酰基、或氰基。Q表示任选被1个或2个碳原子数1～3的烷基取代的亚甲基、氧原子或硫原子。n表示1或2。X表示卤原子。R1、R2与环氧基 的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向。]
[2]根据[1]所述的脂环式环氧化合物，其中，Q为亚甲基，R1、R2、R3、R4、R5、R6及R7为氢原子，n为2。
[3]下述式(1)所示的脂环式环氧化合物的制造方法，
[化学式2]
Figure PCTCN2015073991-appb-000002
[式中，R1、R2、R3及R4相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、或任选羟基被保护基保护且任选具有卤原子的碳原子数1～6的羟基烷基。R5、R6及R7相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、任选形成盐的羧基、取代氧基羰基、任选形成盐的亚磺基、取代氧基亚磺酰基、任选形成盐的磺基、取代氧基磺酰基、或氰基。Q表示任选被1个或2个碳原子数1～3的烷基取代的亚甲基、氧原子或硫原子。n表示1或2。X表示卤原子。R1、R2与环氧基的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向。]
其中，该方法包括：利用氧化剂对下述式(2)所示的脂环式烯烃化合物进行处理，从而生成上述式(1)所示的脂环式环氧化合物。
[化学式3]
Figure PCTCN2015073991-appb-000003
[式中，R1、R2、R3、R4、R5、R6、R7、Q、n及X与式(1)中的含义相同。R1、R2的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向。]
[4]根据[3]所述的脂环式环氧化合物的制造方法，其中，氧化剂为过氧 化氢、或由过氧化氢衍生的过酸。
[5]根据[3]或[4]所述的脂环式环氧化合物的制造方法，其中，Q为亚甲基，R1、R2、R3、R4、R5、R6及R7为氢原子，n为2。
[6]下述式(4)所示的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法，
[化学式4]
Figure PCTCN2015073991-appb-000004
[式中，R1、R2、R3及R4相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、或任选羟基被保护基保护且任选具有卤原子的碳原子数1～6的羟基烷基。R5、R6及R7相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、任选形成盐的羧基、取代氧基羰基、任选形成盐的亚磺基、取代氧基亚磺酰基、任选形成盐的磺基、取代氧基磺酰基、或氰基。Q表示任选被1个或2个碳原子数1～3的烷基取代的亚甲基、氧原子或硫原子。n表示1或2。R1与羟基的空间上的位置任选为内向或外向。]
其中，该方法包括：
将下述式(1)所示的脂环式环氧化合物水解而得到下述式(3)所示的化合物，再进行环化反应，从而生成上述式(4)所示的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物。
[化学式5]
Figure PCTCN2015073991-appb-000005
[式中，R1、R2、R3、R4、R5、R6、R7、Q及n与式(4)中的含义相同。X 表示卤原子。R1、R2与环氧基的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向。]
[化学式6]
Figure PCTCN2015073991-appb-000006
[式中，R1、R2、R3、R4、R5、R6、R7、Q及n与式(4)中的含义相同。M表示氢原子、碱金属、碱土金属、或季铵基。R1、R2与环氧基的空间上的位置、R7与S(O)nOM基的空间上的位置分别任选为内向或外向。]
[7]根据[6]所述的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法，其中，Q为亚甲基，R1、R2、R3、R4、R5、R6及R7为氢原子，n为2。
发明的效果
通过使用本发明的脂环式环氧化合物作为原料，可以利用工业上安全且有效的方法制造2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物。通过将利用该方法而得到的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物作为原料，可以得到4-氧-5-硫杂三环[4.2.1.03，7]壬烷衍生物(例如，具有聚合性基团的衍生物等)，其在衍生为聚合物等的情况下可以在保持耐药品性等稳定性的同时提高水解性及水解后相对于水的溶解性，是作为高功能性高分子等的单体成分等而有用的化合物。
附图说明
[图1]实施例1中得到的式(iia)所示的化合物的1H-NMR谱的谱图。
[图2]实施例1中得到的式(2a)所示的化合物(使用二氯甲烷作为反应溶剂的情况下)的1H-NMR谱的谱图。
[图3]实施例1中得到的式(2a)所示的化合物(使用乙腈作为反应溶剂的情况下)的1H-NMR谱的谱图。
[图4]实施例1中得到的式(1a)所示的化合物(使用过氧化氢作为氧化剂的情况下)的1H-NMR谱的谱图。
[图5]实施例1中得到的式(1a)所示的化合物(使用间氯过苯甲酸作为氧化剂的情况下)的1H-NMR谱的谱图。
[图6]实施例1中得到的式(4a)所示的化合物的1H-NMR谱的谱图。
具体实施方式
<式(1)所示的化合物>
本发明的脂环式环氧化合物是下述式(1)所示的化合物(具有磺酰卤或亚磺酰卤部位的脂环式环氧化合物)。式(1)中，R1、R2、R3及R4相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、或任选羟基(羟基部分)被保护基保护且任选具有卤原子的碳原子数1～6的羟基烷基。式(1)中，R5、R6及R7相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、任选形成盐的羧基、取代氧基羰基、任选形成盐的亚磺基、取代氧基亚磺酰基、任选形成盐的磺基、取代氧基磺酰基、或氰基。Q表示任选被1个或2个碳原子数1～3的烷基取代的亚甲基、氧原子或硫原子。n表示1或2。
[化学式7]
Figure PCTCN2015073991-appb-000007
作为上述卤原子，可列举例如：氟原子、氯原子、溴原子等。作为碳原子数1～6的烷基，可列举例如：甲基、乙基、丙基、异丙基、丁基、异丁基、仲丁基、叔丁基、戊基、己基等。其中，优选碳原子数1～3的烷基、更优选甲基。作为具有卤原子的碳原子数1～6的烷基，可列举例如：氯甲基等氯代烷基；三氟甲基、2，2，2-三氟乙基、五氟乙基等氟代烷基(优选碳原子数1～3的氟代烷基)等。
作为碳原子数1～6的羟基烷基，可列举例如：羟基甲基、2-羟基乙基、1-羟基乙基、3-羟基丙基、2-羟基丙基、4-羟基丁基、6-羟基己基等。作为具有卤原子的碳原子数1～6的羟基烷基，可列举例如：二氟羟基甲基、1，1-二氟-2-羟基乙基、2，2-二氟-2-羟基乙基、1，1，2，2-四氟-2-羟基乙基等。在任选具 有卤原子的碳原子数1～6的羟基烷基中，优选碳原子数为1或2(特别是碳原子数为1)的羟基烷基或羟基卤代烷基。作为任选具有卤原子的碳原子数1～6的羟基烷基的羟基的保护基，可列举在有机合成领域通常被用作羟基的保护基的保护基，例如：甲基、甲氧基甲基等可与构成羟基的氧原子共同形成醚或缩醛键的基团；乙酰基、苯甲酰基等可与构成羟基的氧原子共同形成酯键的基团等。作为羧基、亚磺基、磺基的盐，可列举碱金属盐、碱土金属盐、过渡金属盐等。
作为上述取代氧基羰基，可列举例如：甲氧基羰基、乙氧基羰基、异丙基氧基羰基、丙氧基羰基等烷氧基羰基(C1-4烷氧基-羰基等)；乙烯氧基羰基、烯丙氧基羰基等烯氧基羰基(C2-4烯氧基-羰基等)；环己基氧基羰基等环烷基氧基羰基；苯氧基羰基等芳氧基羰基等。作为取代氧基亚磺酰基、取代氧基磺酰基，可列举例如：与上述取代氧基羰基对应的取代氧基亚磺酰基、取代氧基磺酰基。Q中，作为任选取代在亚甲基上的碳原子数1～3的烷基，可列举例如：甲基、乙基、丙基等。作为被1个或2个碳原子数1～3的烷基取代了的亚甲基，可列举例如：甲基亚甲基、二甲基亚甲基等。
作为R1、R2、R3及R4，它们相同或不同，优选表示：氢原子；甲基、三氟甲基等碳原子数1～3的烷基或卤代烷基；羟基任选被保护基保护的碳原子数1～3的羟基烷基或羟基卤代烷基(特别是羟基甲基、乙酰氧基甲基等羟基被保护基保护了的羟基甲基)等，更优选为氢原子。作为R5、R6及R7，它们相同或不同，优选表示：氢原子；甲基、三氟甲基等碳原子数1～3的烷基或卤代烷基(特别是甲基、卤代甲基)；取代氧基羰基；氰基，更优选为氢原子。另外，作为n，优选为2，作为Q，优选为亚甲基。
式(1)中，X表示卤原子。作为卤原子，可列举例如：氟原子、氯原子、溴原子等。
式(1)中的R1、R2与环氧基在空间上的位置任选为内向或外向。另外，式(1)中的R7与S(O)nX基在空间上的位置任选为内向或外向。
作为式(1)所示的化合物的代表例，可列举下式所示的化合物(包含各立体异构体)。需要说明的是，下述式中，X及n分别表示与式(1)相同的含义。下式中，Ac表示乙酰基。
[化学式8]
Figure PCTCN2015073991-appb-000008
[化学式9]
Figure PCTCN2015073991-appb-000009
[化学式10]
Figure PCTCN2015073991-appb-000010
本发明的脂环式环氧化合物的制造方法没有特殊限制，例如，可以通过对下述式(2)所示的化合物(脂环式烯烃化合物)利用氧化剂进行处理，从而生成本发明的脂环式环氧化合物。
[化学式11]
Figure PCTCN2015073991-appb-000011
式(2)中，R1、R2、R3、R4、R5、R6、R7、Q、n及X分别与式(1)中的含义相同(分别与式(1)中的R1、R2、R3、R4、R5、R6、R7、Q、n及X相对应)。在式(2)所示的化合物中，R1、R2在空间上的位置、R7与S(O)nX基在空间上的位置分别任选为内向或外向。
式(2)所示的化合物可通过公知或惯用的方法制造，没有特殊限制，例如， 可以如下所示地，通过使下述式(ii)所示的化合物(不饱和磺酰卤或不饱和亚磺酰卤)与下述式(iii)所示的化合物(环戊二烯衍生物、呋喃衍生物、或噻吩衍生物)进行狄尔斯-阿尔德反应而制造。
[化学式12]
Figure PCTCN2015073991-appb-000012
式(ii)中的R5、R6、R7、n及X分别与式(1)中的含义相同(分别与式(1)中的R5、R6、R7、n及X相对应)。另外，式(iii)中的R1、R2、R3、R4及Q分别与式(1)中的含义相同(分别与式(1)中的R1、R2、R3、R4及Q相对应)。
作为式(ii)所示的化合物，可列举例如：乙烯基磺酸、α-甲基乙烯基磺酸、β-甲基乙烯基磺酸、α-三氟甲基乙烯基磺酸、β-三氟甲基乙烯基磺酸、α-氰基乙烯基磺酸、β-氰基乙烯基磺酸、α-羧基乙烯基磺酸、β-羧基乙烯基磺酸等不饱和磺酸的卤化物；与这些化合物对应的不饱和亚磺酸的卤化物等。作为式(iii)所示的化合物，可列举例如：1，3-环戊二烯、1-甲基-1，3-环戊二烯、2-甲基-1，3-环戊二烯、5-甲基-1，3-环戊二烯、1，2-二甲基-1，3-环戊二烯、1，4-二甲基-1，3-环戊二烯、2，3-二甲基-1，3-环戊二烯、1，2，3，4-四甲基-1，3-环戊二烯、1，2，3，4，5-五甲基-1，3-环戊二烯、1-羟基甲基-1，3-环戊二烯、1，4-双(羟基甲基)-1，3-环戊二烯、2，3-双(羟基甲基)-1，3-环戊二烯、1-乙酰氧基甲基-1，3-环戊二烯、1，4-双(乙酰氧基甲基)-1，3-环戊二烯、2，3-双(乙酰氧基甲基)-1，3-环戊二烯等环戊二烯衍生物(Q＝CH2的化合物)；呋喃、2-甲基呋喃、3-甲基呋喃、2，5-二甲基呋喃、3，4-二甲基呋喃、2，3，4，5-四甲基呋喃、2-羟基甲基呋喃、2，5-双(羟基甲基)呋喃、2-乙酰氧基甲基呋喃、2，5-双(乙酰氧基甲基)呋喃等呋喃衍生物(Q＝O的化合物)；与上述呋喃衍生物相对应的噻吩衍生物(Q＝S的化合物)等。
式(ii)所示的化合物与式(iii)所示的化合物的反应可在溶剂的存在下或非存在下进行。作为溶剂，可列举例如：乙酸乙酯等酯；乙酸等有机酸；叔丁醇等醇；氯仿、二氯甲烷、1，2-二氯乙烷等卤代烃；苯等芳香族烃；己烷、 庚烷、辛烷等脂肪族烃；环己烷等脂环式烃；N，N-二甲基甲酰胺、N，N-二甲基乙酰胺等酰胺；乙腈、丙腈、苯甲腈等腈；乙醚、四氢呋喃(THF)等链状或环状醚等。溶剂可以单独使用一种，也可以将两种以上组合使用。
上述反应中，为了使反应速度、反应的选择性(立体选择性等)提高，可以在体系内添加路易斯酸。作为路易斯酸，没有特殊限制，可列举例如：AlCl3、SnCl4、TiCl4、BF3、ZnI2等。进行上述反应的温度(反应温度)可根据反应原料的种类等而适当选择，没有特殊限制，但优选为-80～300℃、更优选为-70～250℃。通常，上述反应在常压或加压下进行。另外，上述反应可以按照分批式、半分批式、连续式等中的任意形式进行。经上述反应而生成的式(2)所示的化合物可通过例如过滤、浓缩、蒸馏、提取、晶析、重结晶、柱色谱法等分离方法、或由这些方法组合而成的分离方法来进行分离纯化。
需要说明的是，上述式(ii)所示的化合物可通过公知或惯用的方法制造，没有特殊限制，例如，可以如下所示地通过下述式(i)所示的化合物的脱卤化氢反应来制造。
[化学式13]
Figure PCTCN2015073991-appb-000013
式(i)中的R5、R6、R7、n及X分别与式(1)中的含义相同(分别与式(1)中的R5、R6、R7、n及X相对应)。式(i)中的Y表示卤原子，可列举例如氯原子、溴原子、碘原子等。上述反应(脱卤化氢反应)可以利用公知惯用的方法实施，没有特殊限制，例如，可以按照日本特开2010-83873号公报、J.Am.Chem.Soc.，1954，76，1926中公开的方法等实施。
作为与式(2)所示的化合物反应的氧化剂(用于对式(2)所示的化合物进行处理的氧化剂)，可使用公知或惯用的氧化剂，没有特殊限制，可列举例如：过氧化物(特别是过氧化氢)、或过酸(特别是由过氧化氢衍生的过酸，例如，后述的使用了过氧化氢的平衡过酸等)等。作为上述过氧化物，可列举例如：过氧化氢、过氧化物、氢过氧化物、过氧酸、过氧酸的盐等。作为过氧化氢，也可以使用纯粹的过氧化氢，但从操作性的方面出发，通常以在适当的溶剂(例如水)中稀释的形态(例如，30重量％左右的过氧化氢水溶液的形态)使用。 上述反应(式(2)所示的化合物与氧化剂的反应)中的过氧化氢等过氧化物的使用量没有特殊限制，相对于式(2)所示的化合物1摩尔，优选为0.9～5摩尔、更优选为0.9～3摩尔、进一步优选为0.95～2摩尔。
作为上述过酸，可列举例如：过甲酸、过乙酸、过丙酸、三氟过乙酸、过苯甲酸、间氯过苯甲酸、单过氧苯二甲酸等有机过酸；高锰酸等无机过酸等。过酸也可以以盐的形态使用。有机过酸也可以是平衡过酸(例如，平衡过甲酸、平衡过乙酸等)。即，例如可以将甲酸、乙酸等有机酸与过氧化氢组合使用，使它们在体系内生成对应的有机过酸。使用平衡过酸的情况下，作为催化剂，可以添加少量的硫酸等强酸。上述反应(式(2)所示的化合物与氧化剂的反应)中的过酸的使用量没有特殊限制，相对于式(2)所示的化合物1摩尔，优选为0.8～2摩尔、更优选为0.9～1.5摩尔、进一步优选为0.95～1.2摩尔。
上述过氧化氢多与金属化合物共同使用。作为上述金属化合物，可列举例如：包含W、Mo、V、Mn、Re等金属元素的氧化物、含氧酸或其盐、硫化物、卤化物、卤氧化物、硼化物、碳化物、硅化物、氮化物、磷化物、过氧化物、络合物(无机络合物及有机络合物)、有机金属化合物等。这些金属化合物可以单独使用一种，也可以将两种以上组合使用。
作为上述氧化物，可列举例如：氧化钨(WO2、WO3等)；氧化钼(MoO2、MoO3等)；氧化钒(VO、V2O3、VO2、V2O5等)；氧化锰(MnO、Mn2O3、Mn3O4、MnO2、Mn2O7等)；包含W、Mo、V、Mn等金属元素的复合氧化物等。
作为上述含氧酸，除了例如钨酸、钼酸、钒酸、锰酸等以外，还可以列举：同多钨酸、同多钼酸、同多钒酸等同多酸；磷钨酸、硅钨酸、磷钼酸、硅钼酸、磷钼钒酸等由上述金属元素和其它元素等构成的杂多酸等。作为上述杂多酸中的其它元素等，优选磷或硅，更优选为磷。
作为上述含氧酸的盐，可列举例如：上述含氧酸的钠盐、钾盐等碱金属盐；镁盐、钙盐、钡盐等碱土金属盐；铵盐；过渡金属盐等。含氧酸的盐(例如，杂多酸的盐)也可以是将相当于阳离子的氢原子的一部分替换为其它阳离子而成的盐。
作为包含金属元素的过氧化物，可列举例如：过氧钨酸、过氧钼酸、过氧钒酸等过氧酸；上述过氧酸的碱金属盐、碱土金属盐、铵盐、过渡金属盐等过氧酸的盐；高锰酸等过酸；上述过酸的碱金属盐、碱土金属盐、铵盐、 过渡金属盐等过酸的盐等。
与上述过氧化氢共同使用的金属化合物的使用量没有特殊限制，但优选相对于式(2)所示的化合物1摩尔为0.0001～2摩尔、更优选为0.0005～0.5摩尔、进一步优选为0.001～0.2摩尔。
式(2)所示的化合物与氧化剂的反应可在溶剂的存在下或非存在下进行。作为溶剂，可使用公知或惯用的溶剂，没有特殊限制，可列举：叔丁醇等醇；氯仿、二氯甲烷、1，2-二氯乙烷等卤代烃；苯等芳香族烃；己烷、庚烷、辛烷等脂肪族烃；环己烷等脂环式烃；N，N-二甲基甲酰胺、N，N-二甲基乙酰胺等酰胺；乙腈、丙腈、苯甲腈等腈；乙醚、四氢呋喃等链状或环状醚；乙酸乙酯等酯；乙酸等有机酸；水等。溶剂可以单独使用一种，也可以将两种以上组合使用。另外，使用溶剂的情况下，反应可以在均相体系中进行，也可以在非均相体系、二相体系中进行。需要说明的是，在非均相体系中进行反应的情况下，多使用水、或包含水的溶剂作为溶剂。
使式(2)所示的化合物与氧化剂反应时的温度(反应温度)可以考虑到反应速度及反应选择性等而适当选择，没有特殊限制，但优选为0～100℃、更优选为10～80℃。上述反应可以按照分批式、半分批式、连续式等中的任意形式进行，对于本说明书中记载的其它反应而言也同样。
通过上述反应，式(2)所示的化合物所具有的碳-碳双键发生环氧化，生成式(1)所示的化合物(本发明的脂环式环氧化合物)。通过上述反应而生成的式(1)所示的化合物可通过例如过滤、浓缩、蒸馏、提取、晶析、重结晶、柱色谱法等分离方法、或由这些方法组合而成的分离方法等公知或惯用的纯化方法进行分离纯化。
本发明的脂环式环氧化合物(式(1)所示的化合物)可被用作涂料、功能性高分子的原料、医药、农药及其它精细化学品的原料等。特别是，本发明的脂环式环氧化合物特别优选作为可被用作涂料、功能性高分子的原料、医药、农药及其它精细化学品的原料的下述式(4)所示的化合物(2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物)的原料使用。通过将本发明的脂环式环氧化合物作为原料使用，可以利用工业上能够安全且有效地实施的方法制造式(4)所示的化合物。
[化学式14]
Figure PCTCN2015073991-appb-000014
式(4)中，R1、R2、R3、R4、R5、R6、R7、Q及n与式(1)中的含义相同(分别与式(1)中的R1、R2、R3、R4、R5、R6、R7、Q及n相对应)。需要说明的是，R1与羟基的空间上的位置任选为内向或外向。
<式(4)所示的化合物的制造方法>
使用本发明的脂环式环氧化合物作为原料的式(4)所示的化合物(2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物)的制造方法(也称为“本发明的制造方法”)，是将式(1)所示的化合物(本发明的脂环式环氧化合物)水解而得到下述式(3)所示的化合物(脂环式环氧化合物)，再进行环化反应，生成式(4)所示的化合物的方法。
[化学式15]
Figure PCTCN2015073991-appb-000015
式(3)中，R1、R2、R3、R4、R5、R6、R7、Q及n与式(1)(即，式(4))中的含义相同(分别与式(1)中的R1、R2、R3、R4、R5、R6、R7、Q及n相对应)。式(3)中，M表示氢原子、碱金属、碱土金属、或季铵基。需要说明的是，R1、R2与环氧基的空间上的位置、R7与S(O)nOM基的空间上的位置分别任选为内向或外向。
作为M的碱金属，可列举例如钠、钾等。作为M的碱土金属，可列举例如镁、钙、钡等。作为M的季铵基，可列举例如：后述的叔胺类、含氮芳香族化合物中的氮原子经阳离子化(例如，基于质子化、烷基化的阳离子化)而形成的基团(例如，NH4 +；Me3NH+、Et3NH+等叔烷基铵离子；吡啶鎓离子等)等。
将式(1)所示的化合物水解而得到式(3)所示的化合物的方法没有特殊限制，可采用能够将式(1)中的S(O)nX基转换为S(O)nOM基的公知惯用的水解方法。作为水解的方法，可列举例如：在酸或碱的存在下进行水解的方法、在不存在酸及碱的情况下进行水解的方法等。其中，从反应速度及收率的观点出发，优选在碱的存在下进行水解的方法。
在式(1)所示化合物的水解中，可使用公知或惯用的碱，没有特殊限制，可列举例如：氢氧化锂、氢氧化钠、氢氧化钾、氢氧化铯等碱金属的氢氧化物；氢氧化镁、氢氧化钙、氢氧化钡等碱土金属的氢氧化物；碳酸锂、碳酸钠、碳酸钾、碳酸铯等碱金属的碳酸盐；碳酸镁等碱土金属的碳酸盐；碳酸氢锂、碳酸氢钠、碳酸氢钠、碳酸氢钾、碳酸氢铯等碱金属的碳酸氢盐；乙酸锂、乙酸钠、乙酸钾、乙酸铯等碱金属的有机酸盐(例如，乙酸盐)；乙酸镁等碱土金属的有机酸盐(例如，乙酸盐)；甲醇锂、甲醇钠、乙醇钠、异丙醇钠、乙醇钾、叔丁醇钾等碱金属的醇盐；酚钠等碱金属的酚盐；氨；链状脂肪族叔胺[例如，三甲胺、三乙胺、三丙胺、三丁胺、二异丙基乙基胺等]、环状脂肪族叔胺[例如，N-甲基吡咯烷、N-甲基哌啶、N-甲基吗啉、1，4-二氮杂双环[2.2.2]辛烷、1，5-二氮杂双环[4.3.0]壬烷-5-烯、1，8-二氮杂双环[5.4.0]十一碳-7-烯等]、芳香族叔胺[例如，N，N-二甲基苯胺等]等胺类；吡咯衍生物[例如，吡咯、N-甲基吡咯等]、咪唑衍生物[例如，咪唑、1-甲基咪唑、2-甲基咪唑、4-甲基咪唑等]、三唑衍生物[例如，三唑等]、吡啶衍生物[例如，吡啶、4-(二甲基氨基)吡啶、2-甲基吡啶、3-甲基吡啶、4-甲基吡啶、2，4-二甲基吡啶、2，6-二甲基吡啶、3，4-二甲基吡啶、3，5-二甲基吡啶、2-甲氧基吡啶、2-氰基吡啶、3-氰基吡啶、4-氰基吡啶、联吡啶、三甲基吡啶、喹啉、异喹啉等]、哒嗪衍生物[例如，哒嗪、3-甲基哒嗪、4-甲基哒嗪等]、嘧啶衍生物[例如，嘧啶、4-甲基嘧啶等]、吡嗪衍生物[例如，吡嗪、2-甲基吡嗪等]、三嗪衍生物[例如，三嗪等]等含氮芳香族化合物(含氮芳香族杂环式化合物)等。碱可以单独使用一种，也可以将两种以上组合使用。另外，碱也可以以溶解或分散于水等溶剂中的形态使用。碱的使用量没有特殊限制，但优选相对于式(1)所示的化合物1摩尔为1～10摩尔、更优选为1～5摩尔。
在式(1)所示的化合物的水解中，可使用公知或惯用的酸，没有特殊限制，可列举例如：盐酸、硫酸、硝酸、磷酸、硼酸等无机酸；磷酸酯；乙酸、甲酸、三氟乙酸等羧酸；甲磺酸、三氟甲磺酸、对甲苯磺酸等磺酸；活性白土 等固体酸；氯化铁等路易斯酸等。酸可以单独使用一种，也可以将两种以上组合使用。另外，酸也可以以溶解或分散于水等溶剂中的形态使用。酸的使用量没有特殊限制，但优选相对于式(1)所示的化合物1摩尔为1～10摩尔、更优选为1～5摩尔。
上述反应(式(1)所示的化合物的水解)可在溶剂的存在下或非存在下进行。作为溶剂，可使用公知或惯用的溶剂，没有特殊限制，可使用在上述式(2)所示的化合物与氧化剂的反应中使用的溶剂等。另外，上述反应的反应体系可以由有机层和水层混和而达到均一，也可以不进行混和而是成为非均相体系、二相体系。对于基质(例如，式(1)所示的化合物、酸、碱等)，将它们溶解在溶剂中至可使反应进行的程度即可，可以是溶液状态，也可以是分散状态。另外，还可以将水本身作为溶剂使用。溶剂可以单独使用一种，也可以将两种以上组合使用。
上述反应中使用的水的量没有特殊限制，但优选相对于式(1)所示的化合物1摩尔为1～1000摩尔、更优选为1～100摩尔。
使上述反应进行的温度(反应温度)没有特殊限制，但优选为0～100℃、更优选为10～50℃。使上述反应进行的时间(反应时间)没有特殊限制，例如可以从0.01～100小时的范围中适当选择。
进行上述反应的方法只要是式(1)所示的化合物与水共存的实施方式(优选为进一步还共存有酸或碱(特别是碱)的实施方式)即可，没有特殊限制。可列举例如：向式(1)所示的化合物或其溶液中添加水(例如，溶解有酸或碱的水溶液)的方法、向水(例如，溶解有酸或碱的水溶液)中添加式(1)所示的化合物或其溶液的方法等。
需要说明的是，经上述反应而生成的式(3)所示的化合物可以直接(不进行纯化)供给至后续反应(生成式(4)所示的化合物的反应)，也可以在进行纯化之后供给至后续反应。作为纯化方法，可采用公知或惯用的方法，没有特殊限制，可列举例如过滤、浓缩、蒸馏、提取、晶析、重结晶、柱色谱法等分离方法、或由这些方法组合而成的分离方法等。
接着，使式(3)所示的化合物(脂环式环氧化合物)进行环化反应而生成式(4)所示的化合物。在M为氢原子的情况下，上述环化反应例如可仅通过使式(3)所示的化合物溶解于溶剂中来进行。另一方面，M为碱金属、碱土金属或季铵基的情况下，作为使上述环化反应进行的方法，可列举在酸的存在 下根据需要而进行加热的方法。
作为上述酸，可使用公知或惯用的酸，没有特殊限制，可列举例如：盐酸、硫酸、硝酸、磷酸、硼酸等无机酸；磷酸酯；乙酸、甲酸、三氟乙酸等羧酸；甲磺酸、三氟甲磺酸、对甲苯磺酸等磺酸；活性白土等固体酸；氯化铁等路易斯酸等。需要说明的是，酸可以单独使用一种，也可以将两种以上组合使用。另外，酸也可以以溶解或分散于水等溶剂中的形态使用。
上述反应(式(3)所示的化合物的环化反应)可在溶剂的存在下或非存在下进行。作为溶剂，可使用公知或惯用的溶剂，没有特殊限制，可使用在上述式(2)所示的化合物与氧化剂的反应中使用的溶剂等。另外，还可以将水本身作为溶剂使用。溶剂可以单独使用一种，也可以将两种以上组合使用。
使上述反应进行的温度(反应温度)没有特殊限制，但优选为10～100℃、更优选为20～80℃。使上述反应进行的时间(反应时间)没有特殊限制，但优选为1～40小时、更优选为5～30小时。
经上述反应而生成的式(4)所示的化合物(2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物)可通过例如过滤、浓缩、蒸馏、提取、晶析、重结晶、柱色谱法等分离方法、或由这些方法组合而成的分离方法等公知或惯用的纯化手段进行分离纯化。
需要说明的是，本发明的制造方法中的式(1)所示化合物的水解反应、和式(3)所示化合物的环化反应可以连续地进行，也可以非连续地进行。
本发明的制造方法也可以进一步包含生成式(1)所示的化合物的工序(例如，利用氧化剂对上述式(2)所示的化合物进行处理的工序)、其它工序(例如，生成上述式(2)所示的化合物的工序等)。这些工序、及上述的进行水解反应、环化反应的工序可以连续地进行，也可以非连续地进行。
根据本发明的制造方法，可以利用工业上安全且有效的方法制造式(4)所示的化合物。具体而言，本发明的制造方法不像例如不经由式(1)所示的化合物的日本专利5352387号中记载的方法那样存在副产吡啶类的N-氧化物等具有爆炸性的化合物的隐患，并且能够以高收率生成式(4)所示的化合物。
通过本发明的制造方法得到的式(4)所示的化合物可优选作为例如涂料、功能性高分子的原料、医药、农药及其它精细化学品的原料等使用。例如，通过向式(4)所示化合物的羟基部分导入聚合性基团(例如，丙烯酰基、甲基丙烯酰基等)，可以得到在衍生为聚合物等的情况下可以在保持耐药品性等 稳定性的同时提高水解性及水解后相对于水的溶解性、作为高功能性高分子等的单体成分等有用的4-氧-5-硫杂三环[4.2.1.03，7]壬烷衍生物。聚合性基团向式(4)所示的化合物的导入没有特殊限制，可按照例如日本特开2007-31355号公报中记载的方法等进行。
实施例
以下，结合实施例对本发明进行更为详细的说明，但本发明并不限定于这些实施例。需要说明的是，产物的鉴定通过1H-NMR谱测定(溶剂：CDCl3)来进行。
实施例1
按照下述反应路线图制造了式(1a)所示的化合物。另外，以式(1a)所示的化合物为原料制造了式(4a)所示的化合物。
[化学式16]
Figure PCTCN2015073991-appb-000016
[步骤1：式(iia)所示化合物的合成]
在配备有搅拌器、温度计及滴液漏斗的内容量500ml的三颈烧瓶中添加式(ia)所示的化合物(纯度98％、20.00g、120.23mmol)及二氯甲烷(100ml)，进行搅拌的同时冷却至-5℃。接着，以不使内温超过0℃的速度、经30分钟以上滴加的方式向其中加入将2，6-二甲基吡啶(纯度98％、14.46g、1.1当量)溶解于二氯甲烷(100ml)而成的溶液。一边将所得混合物自然温热至室温，一边继续搅拌40分钟。接着，冷却至0℃之后，缓慢加入经过冰冷的硫酸(1％、125ml)，然后将混合物在同温度(0℃)下搅拌2分钟。然后，分离出二氯甲烷层，利用100ml的水洗涤2次，并用硫酸钠进行干燥，进行浓缩，得到了浅 褐色的油的形式的产物(14.69g、收率96％)。由该产物的1H-NMR谱测定结果可以确认，生成了式(iia)所示的化合物(参见图1)。
需要说明的是，关于步骤1的反应，通过不同于上述反应路线图的方法，具体而言，在如下所述地使用乙酸乙酯作为溶剂的情况下也同样能够实施。
[步骤1(其它方式)：使用乙酸乙酯作为溶剂]
在配备有搅拌器、温度计及滴液漏斗的内容量500ml的三颈烧瓶中添加式(ia)所示的化合物(纯度98％、20.00g、120.23mmol)及乙酸乙酯(200ml)，进行搅拌的同时冷却至-5℃。接着，以不使内温超过0℃的速度、经30分钟以上滴加的方式向其中加入将2，6-二甲基吡啶(纯度98％、14.46g、1.1当量)溶解于乙酸乙酯(100ml)而成的溶液。此时，析出了白色固体。一边将所得混合物自然温热至室温，一边继续搅拌40分钟。接着，冷却至0℃之后，缓慢加入经过冰冷的硫酸(1％、125ml)，然后将混合物在同温度(0℃)下搅拌2分钟。然后，分离出乙酸乙酯层，用100ml的水洗涤2次，并用硫酸钠进行干燥，进行浓缩，得到了浅褐色的油的形式的产物(13.64g、收率90％)。由1H-NMR谱测定的结果可以确认，与使用二氯甲烷作为溶剂的情况同样地，生成了式(iia)所示的化合物。
[步骤2：式(2a)所示化合物的合成]
在配备有搅拌器、温度计及滴液漏斗的内容量100ml的三颈烧瓶中添加环戊二烯(3.13g、1.2当量)、吩噻嗪(39mg、0.005当量)及二氯甲烷(50ml)，进行搅拌的同时冷却至-10℃。接着，以不使内温超过-5℃的速度、经1小时以上滴加的方式向其中加入使式(iia)所示的化合物(5.00g、39.51mmol)溶解于二氯甲烷(10ml)而成的溶液。滴加结束后，将所得溶液于-10～-5℃继续搅拌3小时。然后，进行减压的同时于25～30℃进行浓缩，得到了淡橙色的油的形式的粗产物(7.61g、定量的、内向/外向＝9.09/1)。由该产物的1H-NMR谱测定的结果可以确认，生成了式(2a)所示的化合物(参见图2)。
需要说明的是，式(2a)所示的化合物于-10℃发生了凝固。
需要说明的是，关于步骤2的反应，通过不同于上述反应路线图的方法，具体而言，在如下所述地使用乙腈作为溶剂的情况下也同样能够实施。
[步骤2(其它方式)：使用乙腈作为溶剂]
在配备有搅拌器、温度计及滴液漏斗的内容量100ml的三颈烧瓶中添加环戊二烯(0.63g、1.2当量)、吩噻嗪(8mg、0.005当量)及乙腈(15ml)，进行搅 拌的同时冷却至-10℃。接着，以不使内温超过-5℃的速度、经1小时以上滴加的方式向其中加入使式(iia)所示的化合物(1.00g、7.90mmol)溶解于乙腈(10ml)而成的溶液。滴加结束后，将所得溶液于-10～-5℃继续搅拌3小时。然后，进行减压的同时于35～40℃进行浓缩，得到了淡橙色的油的形式的粗产物(1.52g、定量的、内向/外向＝10.7/1)。由该产物的1H-NMR谱测定的结果可以确认，生成了式(2a)所示的化合物(参见图3)。
[步骤3；式(1a)所示的化合物的合成]
在配备有搅拌器及温度计的内容量100ml的三颈烧瓶中边搅拌边添加式(2a)所示的化合物(1.00g、5.19mmol)、甲酸(98％、0.49g、2.0当量)、草酸(脱水)(20mg、0.03当量)及乙腈(15ml)。接着，于25℃经1分钟以上利用注射器进行滴加而加入30％过氧化氢水溶液(0.88g、1.5当量)。接着，将所得溶液加热至50℃，搅拌18小时。然后，将反应混合物冷却至5～10℃，缓慢加入10％亚硫酸钠水溶液直到利用碘化钾淀粉试纸无法检测到过酸为止。对于由此得到的产物，不进行纯化而在后续步骤中使用。由该产物的1H-NMR谱测定的结果可以确认，生成了式(1a)所示的化合物(2，3-环氧双环[2.2.1]庚烷-2-烯-5-磺酰氯)(参见图4)。
需要说明的是，关于步骤3的反应，通过不同于上述反应路线图的方法，具体而言，在如下所述地使用间氯过苯甲酸(mCPBA)作为氧化剂的情况下也同样能够实施。
[步骤3(其它方式)：使用mCPBA作为氧化剂]
在配备有搅拌器、滴液漏斗及温度计的内容量250ml的三颈烧瓶中添加式(2a)所示的化合物(8.00g、41.52mmol)及二氯甲烷(60ml)，进行搅拌的同时冷却至0℃。接着，以不使内温超过5℃的速度进行滴加而加入将mCPBA(75％、10.03g、1.05当量)溶解于二氯甲烷(40ml)而成的溶液。然后，将所得溶液加温至5～10℃，进行搅拌直到式(2a)所示的化合物被完全消耗为止。需要说明的是，式(2a)所示的化合物的消耗可利用TLC进行检查。然后，再次将反应混合物冷却至0℃，缓慢加入10％亚硫酸钠水溶液直到利用碘化钾淀粉试纸无法检测到过酸为止。其后，对于有机层，用10％碳酸氢钠水溶液洗涤1次(直至达到pH＝7～8)、用水(40ml)洗涤1次、用食盐水(40ml)洗涤1次，并用硫酸钠使其干燥，进行浓缩，得到了黄色的油的形式的粗产物(8.3g)。
利用硅胶色谱法(洗脱液：PE(石油醚)/乙酸乙酯＝10/1～5/1)进一步对1.5g黄色的油进行纯化，得到了稍带黄色的白色固体形式的产物(0.39g、收率34％)。由该产物的1H-NMR谱测定的结果可以确认，生成了式(1a)所示的化合物(2，3-环氧双环[2.2.1]庚烷-2-烯-5-磺酰氯)(参见图5)。
[步骤4：式(3a)所示化合物的合成]
在配备有搅拌器、滴液漏斗及温度计的内容量100ml的三颈烧瓶中边搅拌边添加式(1a)所示的化合物(2.00g、9.58mmol)及THF(15ml)。接着，于25℃经3分钟以上滴加将碳酸氢钠(2.01g、2.5当量)溶解于水(20ml)而成的溶液。然后，于该温度将所得悬浮液搅拌1.5小时，不进行纯化而在后续步骤5中使用。
[步骤5：式(4a)所示化合物的合成]
在配备有搅拌器及温度计的内容量100ml的三颈烧瓶中边搅拌添加悬浮液(步骤4中得到的悬浮液)。接着，于25℃经2分钟以上利用注射器进行滴加而加入甲酸(98％、2.25g、5.0当量)。然后，将所得悬浮液加热至50℃，于该温度搅拌18小时。使THF蒸发，利用乙酸乙酯(100ml)稀释残渣。其后，对于有机层，用饱和碳酸氢钠水溶液(30ml)洗涤1次、用水(20ml)洗涤2次、用食盐水(20ml)洗涤1次，并利用硫酸钠使其干燥，进行浓缩，得到了无色的油的形式的粗产物(1.3g)。
利用二异丙基醚(100ml)对该粗产物进行重结晶，得到了白色固体形式的纯粹的产物(0.8g)(其中，根据TLC分析，表明重结晶的滤液中存在大量的产物，因此需要对重结晶的条件进行优化)。由该产物的1H-NMR谱测定的结果可以确认，生成了式(4a)所示的化合物(2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷-2，2-二酮)(参见图6)。
通过步骤1～5而得到的式(4a)所示化合物的以式(ia)所示化合物为基准的连续收率为34％。由此可以确认，根据本发明的制造方法，可以利用工业上安全且有效的方法以良好的收率制造2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物。
实施例2
[由式(ia)所示的化合物连续合成2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷-2，2-二酮]
向500ml的三颈烧瓶中进料式(ia)所示的化合物(50g)及二氯甲烷 (150ml)，冷却至-5℃。以不使液温升高至0℃以上的方式经40分钟向其中滴加将2，6-二甲基吡啶(36.15g)溶解于二氯甲烷(100ml)而成的溶液。滴加结束后，将反应温度缓慢升高至22℃的同时，继续搅拌1.5小时。然后，再次冷却反应液，以不使液温超过10℃的速度滴加硫酸(1％、250g)。滴加结束后，除去水层，将有机层用水(200mL)洗涤2次。将由此得到的反应液作为“反应粗液A”。至此为止，相当于上述的步骤1。
向另外的1L的三颈烧瓶中进料环戊二烯(22.3g)、吩噻嗪(305mg)及二氯甲烷(100ml)，冷却至-10℃。以不使液温超过-5℃的方式经2小时向其中滴加上述的反应粗液A。滴加结束后，于反应温度-10～-5℃继续反应4小时。将由此得到的反应液作为“反应粗液B”。得到反应粗液A之后至此为止，相当于上述的步骤2。
将该反应粗液B保持于5～10℃，加入98％甲酸(34.57g)之后，经10分钟滴加30％过氧化氢水溶液(41.72g)。滴加结束后，于反应温度22℃继续反应40小时。然后，将液温冷却至10℃，以使液温为10～15℃的方式滴加10％亚硫酸钠水溶液(30ml)。滴加结束后，利用碘化钾淀粉试纸确认到，体系中没有过氧化物的残存。将由此得到的反应液作为“反应粗液C”。得到反应粗液B之后至此为止，相当于上述的步骤3。
将氢氧化钠(47.85g)溶解于水(300ml)而得到的氢氧化钠水溶液于15℃经25分钟滴加到上述的反应粗液C中。滴加结束后，将水层和有机层分液，并用水(100ml)洗涤有机层之后，分液出水层并与先前的水层合并。将由此得到的水层作为“反应粗液D”。得到反应粗液C之后至此为止，相当于上述的步骤4。
于液温15℃经5分钟向反应粗液D中滴加98％甲酸(53.3g)。将该反应混合物升温至50℃，继续搅拌18小时。反应结束后，将反应液冷却至室温，使用乙酸乙酯(150ml)进行了2次萃取。合并该乙酸乙酯层，添加5％氢氧化钠水溶液、使pH达到7。然后回收有机层，进行浓缩，由此得到了淡黄色固体形式的目标的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷-2，2-二酮。收量为19.8g、以式(ia)所示的化合物为基准的连续收率为34％、以GC面积为基准的纯度为92％以上。
参考例
[2-甲基丙烯酰氧基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷-2，2-二酮的合成]
以实施例1中得到的式(4a)所示的化合物为原料，按照下述顺序合成了具有聚合性基团的4-氧-5-硫杂三环[4.2.1.03，7]壬烷衍生物。
在100ml的四颈烧瓶中进料2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷-2，2-二酮(5.0g)、硫酸(0.26g)、甲基丙烯酸(22.63g)、对羟基苯甲醚(メトキノン)(0.15g)及甲苯(50.0g)，安装了温度计、及迪安-斯达克装置。调整体系的真空度、使其在液温85℃下发生加热回流，继续反应12小时。反应结束后，用水(50g)对所得有机层进行水洗之后，同样地对有机层用8％碳酸氢钠水溶液洗涤3次、用水洗涤3次。然后，浓缩有机层，通过在添加庚烷50g后进行冷却而使其发生晶析，得到了作为目标物的2-甲基丙烯酰氧基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷-2，2-二酮4.4g。利用气相色谱法(GC)测定的纯度为99.2％、收率为65％。
比较例1
[2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷-2，2-二酮的合成]
使用2-氯乙烷磺酰氯350g作为起始物质，按照日本专利5352387号的参考例1及实施例1的方法合成了2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷-2，2-二酮。收量为51.8g、收率(以2-氯乙烷磺酰氯为基准的连续收率)为6.5％。
工业实用性
本发明的脂环式环氧化合物特别适宜作为可被用作涂料、功能性高分子的原料、医药、农药及其它精细化学品的原料的式(4)所示的化合物的原料使用。通过使用本发明的脂环式环氧化合物作为原料，可利用工业上能够安全且有效地实施的方法制造式(4)所示的化合物。

Claims (7)

  1. 下述式(1)所示的脂环式环氧化合物，
    [化学式1]
    Figure PCTCN2015073991-appb-100001
    式(1)中，
    R1、R2、R3及R4相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、或任选羟基被保护基保护且任选具有卤原子的碳原子数1～6的羟基烷基，
    R5、R6及R7相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、任选形成盐的羧基、取代氧基羰基、任选形成盐的亚磺基、取代氧基亚磺酰基、任选形成盐的磺基、取代氧基磺酰基、或氰基，
    Q表示任选被1个或2个碳原子数1～3的烷基取代的亚甲基、氧原子或硫原子，
    n表示1或2，
    X表示卤原子，
    R1、R2与环氧基的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向。
  2. 根据权利要求1所述的脂环式环氧化合物，其中，
    Q为亚甲基，
    R1、R2、R3、R4、R5、R6及R7为氢原子，
    n为2。
  3. 下述式(1)所示的脂环式环氧化合物的制造方法，
    [化学式2]
    Figure PCTCN2015073991-appb-100002
    式(1)中，
    R1、R2、R3及R4相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、或任选羟基被保护基保护且任选具有卤原子的碳原子数1～6的羟基烷基，
    R5、R6及R7相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、任选形成盐的羧基、取代氧基羰基、任选形成盐的亚磺基、取代氧基亚磺酰基、任选形成盐的磺基、取代氧基磺酰基、或氰基，
    Q表示任选被1个或2个碳原子数1～3的烷基取代的亚甲基、氧原子或硫原子，
    n表示1或2，
    X表示卤原子，
    R1、R2与环氧基的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向，
    其中，该方法包括：
    利用氧化剂对下述式(2)所示的脂环式烯烃化合物进行处理，生成上述式(1)所示的脂环式环氧化合物，
    [化学式3]
    Figure PCTCN2015073991-appb-100003
    式(2)中，
    R1、R2、R3、R4、R5、R6、R7、Q、n及X与式(1)中的含义相同，
    R1、R2的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向。
  4. 根据权利要求3所述的脂环式环氧化合物的制造方法，其中，氧化剂为过氧化氢、或由过氧化氢衍生的过酸。
  5. 根据权利要求3或4所述的脂环式环氧化合物的制造方法，其中，
    Q为亚甲基，
    R1、R2、R3、R4、R5、R6及R7为氢原子，
    n为2。
  6. 下述式(4)所示的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法，
    [化学式4]
    Figure PCTCN2015073991-appb-100004
    式(4)中，
    R1、R2、R3及R4相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、或任选羟基被保护基保护且任选具有卤原子的碳原子数1～6的羟基烷基，
    R5、R6、及R7相同或不同，表示氢原子、卤原子、任选具有卤原子的碳原子数1～6的烷基、任选形成盐的羧基、取代氧基羰基、任选形成盐的亚磺基、取代氧基亚磺酰基、任选形成盐的磺基、取代氧基磺酰基、或氰基，
    Q表示任选被1个或2个碳原子数1～3的烷基取代的亚甲基、氧原子或硫原子，
    n表示1或2，
    R1与羟基的空间上的位置任选为内向或外向，
    其中，该方法包括：
    将下述式(1)所示的脂环式环氧化合物水解而得到下述式(3)所示的化合物，再进行环化反应，生成上述式(4)所示的2-羟基-4-氧杂-5-硫杂三环 [4.2.1.03，7]壬烷衍生物，
    [化学式5]
    Figure PCTCN2015073991-appb-100005
    式(1)中，
    R1、R2、R3、R4、R5、R6、R7、Q及n与式(4)中的含义相同，
    X表示卤原子，
    R1、R2与环氧基的空间上的位置、R7与S(O)nX基的空间上的位置分别任选为内向或外向，
    [化学式6]
    Figure PCTCN2015073991-appb-100006
    式(3)中，
    R1、R2、R3、R4、R5、R6、R7、Q及n与式(4)中的含义相同，
    M表示氢原子、碱金属、碱土金属或季铵基，
    R1、R2与环氧基的空间上的位置、R7与S(O)nOM基的空间上的位置分别任选为内向或外向。
  7. 根据权利要求6所述的2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法，其中，
    Q为亚甲基，
    R1、R2、R3、R4、R5、R6及R7为氢原子，
    n为2。
PCT/CN2015/073991 2015-03-11 2015-03-11 脂环式环氧化合物及其制造方法、以及2-羟基-4-氧杂-5-硫杂三环[4.2.1.03，7]壬烷衍生物的制造方法 Ceased WO2016141563A1 (zh)

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