CN107207457A - Cycloaliphatic epoxy and its manufacture method and the ring [4.2.1.0 of 2 hydroxyl, 4 oxa-, 5 thia three3,7] nonane derivatives manufacture method - Google Patents

Cycloaliphatic epoxy and its manufacture method and the ring [4.2.1.0 of 2 hydroxyl, 4 oxa-, 5 thia three3,7] nonane derivatives manufacture method Download PDF

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CN107207457A
CN107207457A CN201580072340.8A CN201580072340A CN107207457A CN 107207457 A CN107207457 A CN 107207457A CN 201580072340 A CN201580072340 A CN 201580072340A CN 107207457 A CN107207457 A CN 107207457A
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halogen atom
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alkyl
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大野充
张雷涛
刘冰
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Daicel Packaging Systems Co ltd
Daicel Corp
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    • 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
    • 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
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Epoxy Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

It is an object of the invention to provide be used as the ring [4.2.1.0 of 2 hydroxyl, 4 oxa-, 5 thia three3,7] nonane derivatives raw material and useful new cycloaliphatic epoxy.The cycloaliphatic epoxy of the present invention is the compound shown in following formula (1).[in formula, R1、R2、R3And R4It is identical or different, represent hydrogen atom, halogen atom, the alkyl of the optional carbon number 1~6 with halogen atom or optionally the hydroxy alkyl of the carbon number 1~6 of halogen atom is protected and optionally had by protection group to hydroxyl.R5、R6And R7It is identical or different, represent hydrogen atom, halogen atom, alkyl, the carboxyl of optional forming salt, substituted oxy carbonyl, the sulfino of optional forming salt, substituted oxy sulfinyl, the sulfo group of optional forming salt, substituted oxy sulfonyl or the cyano group of the optional carbon number 1~6 with halogen atom.Q is represented optionally by alkyl-substituted methylene, oxygen atom or the sulphur atom of 1 or 2 carbon number 1~3.N represents 1 or 2.X represents halogen atom.R1、R2Position spatially, R with epoxy radicals7With S (O)nThe position spatially of X bases is optionally introversive or export-oriented respectively.]

Description

Cycloaliphatic epoxy and its manufacturing method and 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane derivatives manufacturing method Technical field
The present invention relates to as synthesizing 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane derivatives raw material and useful novel cycloaliphatic epoxy and its manufacturing method, the 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane derivatives are used as the raw material of coating, the raw material of functional high-polymer, medicine, pesticide and other fine chemicals.Moreover, it relates to using above-mentioned cycloaliphatic epoxy as the 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 of raw material3,7] nonane derivatives manufacturing method.
Background technique
Just with the 4- oxygen -5- thia tricyclic [4.2.1.0 of polymerizable group3,7] for nonane derivatives, known its can improve dissolubility relative to water after water-disintegrable and hydrolysis in the case where being derived as polymer etc. while keeping resistance to chemical reagents equistability, it is monomer component as high functionality macromolecule etc. etc. and useful compound (for example, with reference to patent document 1).As being suitable for use as 4- oxygen -5- thia tricyclic [4.2.1.03,7] nonane derivatives raw material 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane derivatives manufacturing method, it has been disclosed that for example by sulfonic acid halide derivative hydrolysis after, handled using oxidant, to obtain 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane derivatives method (referring to patent document 2).
Existing technical literature
Patent document
Patent document 1: Japanese Unexamined Patent Publication 2007-31355 bulletin
Patent document 2: Japanese Patent No. 5352387
Summary of the invention
Problems to be solved by the invention
However, there is no industrially can securely and effectively manufacture 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 in the prior art3,7] nonane derivatives method.In method described in Patent Document 2, such as when using sodium hydroxide as alkali for hydrolysis, yield is low, according to the record of patent document 2, 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 relative to 2- chloroethene alkanesulphonyl chlorides3,7] nonane derivatives yield (continuous yield) be 29%.However, failing to obtain reproducibility, and above-mentioned continuous yield is at most 7% when the present inventor etc. verify for the above method.On the other hand, according to the record of patent document 2, such as when using pyridines as the alkali for being used for hydrolysis, above-mentioned continuous yield reaches as high as 47%, but for the method in this way using pyridines, since pyridines can be brought into the oxidation operation as subsequent handling in the form of sulfonate, there are the hidden danger that by-product has volatile pyridine N-oxides, it is difficult to realize industrial implementation.
Therefore, the purpose of the present invention is to provide be suitable for use as 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane derivatives raw material novel cycloaliphatic epoxy and its manufacturing method.
In addition, another object of the present invention is to provide the 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 that industrially can securely and effectively implement3,7] nonane derivatives manufacturing method.
Solution to the problem
The inventors of the present invention's discovery, by by newfound cycloaliphatic epoxy (2, bicyclic [2.2.1] heptane -2- alkene -5- sulfonic acid halide derivative of 3- epoxy) it is used as raw material, it can use industrial safe and efficient method and obtain the 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 of target3,7] nonane derivatives, and then complete the present invention.
That is, the present invention relates to following proposals.
[1] cycloaliphatic epoxy shown in following formula (1).
[chemical formula 1]
[in formula, R1、R2、R3And R4It is identical or different, indicate hydrogen atom, halogen atom, the alkyl of the optionally carbon atom number 1~6 with halogen atom or optionally hydroxyl by protecting group protection and the hydroxy alkyl of the optionally carbon atom number 1~6 with halogen atom.R5、R6And R7It is identical or different, indicate hydrogen atom, halogen atom, optionally with the alkyl of carbon atom number 1~6, the carboxyl of optional forming salt, substituted oxy carbonyl, the sulfino of optional forming salt, substituted oxy sulfinyl, the sulfo group of optional forming salt, substituted oxy sulfonyl or the cyano of halogen atom.Q indicates alkyl-substituted methylene, oxygen atom or the sulphur atom optionally by 1 or 2 carbon atom number 1~3.N indicates 1 or 2.X indicates halogen atom.R1、R2With epoxy group Position spatially, R7With S (O)nThe position spatially of X base is optionally introversive or export-oriented respectively.]
[2] cycloaliphatic epoxy according to [1], wherein Q is methylene, R1、R2、R3、R4、R5、R6And R7For hydrogen atom, n 2.
[3] manufacturing method of cycloaliphatic epoxy shown in following formula (1),
[chemical formula 2]
[in formula, R1、R2、R3And R4It is identical or different, indicate hydrogen atom, halogen atom, the alkyl of the optionally carbon atom number 1~6 with halogen atom or optionally hydroxyl by protecting group protection and the hydroxy alkyl of the optionally carbon atom number 1~6 with halogen atom.R5、R6And R7It is identical or different, indicate hydrogen atom, halogen atom, optionally with the alkyl of carbon atom number 1~6, the carboxyl of optional forming salt, substituted oxy carbonyl, the sulfino of optional forming salt, substituted oxy sulfinyl, the sulfo group of optional forming salt, substituted oxy sulfonyl or the cyano of halogen atom.Q indicates alkyl-substituted methylene, oxygen atom or the sulphur atom optionally by 1 or 2 carbon atom number 1~3.N indicates 1 or 2.X indicates halogen atom.R1、R2With the position spatially of epoxy group, R7With S (O)nThe position spatially of X base is optionally introversive or export-oriented respectively.]
Wherein, this method comprises: being handled using oxidant ester ring type olefin(e) compound shown in following formula (2), to generate cycloaliphatic epoxy shown in above-mentioned formula (1).
[chemical formula 3]
[in formula, R1、R2、R3、R4、R5、R6、R7, Q, n and X it is identical as the meaning in formula (1).R1、R2Position spatially, R7With S (O)nThe position spatially of X base is optionally introversive or export-oriented respectively.]
[4] manufacturing method of the cycloaliphatic epoxy according to [3], wherein oxidant is peroxide Change hydrogen or the peracid as derived from hydrogen peroxide.
[5] manufacturing method of the cycloaliphatic epoxy according to [3] or [4], wherein Q is methylene, R1、R2、R3、R4、R5、R6And R7For hydrogen atom, n 2.
[6] 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 shown in following formula (4)3,7] nonane derivatives manufacturing method,
[chemical formula 4]
[in formula, R1、R2、R3And R4It is identical or different, indicate hydrogen atom, halogen atom, the alkyl of the optionally carbon atom number 1~6 with halogen atom or optionally hydroxyl by protecting group protection and the hydroxy alkyl of the optionally carbon atom number 1~6 with halogen atom.R5、R6And R7It is identical or different, indicate hydrogen atom, halogen atom, optionally with the alkyl of carbon atom number 1~6, the carboxyl of optional forming salt, substituted oxy carbonyl, the sulfino of optional forming salt, substituted oxy sulfinyl, the sulfo group of optional forming salt, substituted oxy sulfonyl or the cyano of halogen atom.Q indicates alkyl-substituted methylene, oxygen atom or the sulphur atom optionally by 1 or 2 carbon atom number 1~3.N indicates 1 or 2.R1Position spatially with hydroxyl is optionally introversive or export-oriented.]
Wherein, this method comprises:
The hydrolysis of cycloaliphatic epoxy shown in following formula (1) is obtained into following formula (3) compound represented, cyclization is carried out again, to generate 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 shown in above-mentioned formula (4)3,7] nonane derivatives.
[chemical formula 5]
[in formula, R1、R2、R3、R4、R5、R6、R7, Q and n it is identical as the meaning in formula (4).X Indicate halogen atom.R1、R2With the position spatially of epoxy group, R7With S (O)nThe position spatially of X base is optionally introversive or export-oriented respectively.]
[chemical formula 6]
[in formula, R1、R2、R3、R4、R5、R6、R7, Q and n it is identical as the meaning in formula (4).M indicates hydrogen atom, alkali metal, alkaline-earth metal or quaternary ammonium group.R1、R2With the position spatially of epoxy group, R7With S (O)nThe position spatially of OM base is optionally introversive or export-oriented respectively.]
[7] the 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 according to [6]3,7] nonane derivatives manufacturing method, wherein Q is methylene, R1、R2、R3、R4、R5、R6And R7For hydrogen atom, n 2.
The effect of invention
By using cycloaliphatic epoxy of the invention as raw material, industrial safe and efficient method manufacture 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 can use3,7] nonane derivatives.As will obtained from this method 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane derivatives are as raw material, available 4- oxygen -5- thia tricyclic [4.2.1.03,7] nonane derivatives (such as, derivative etc. with polymerizable group), it can improve dissolubility relative to water after water-disintegrable and hydrolysis in the case where being derived as polymer etc. while keeping resistance to chemical reagents equistability, be monomer component as high functionality macromolecule etc. etc. and useful compound.
Detailed description of the invention
Formula (iia) compound represented obtained in [Fig. 1] embodiment 11The spectrogram of H-NMR spectrum.
Formula (2a) compound represented obtained in [Fig. 2] embodiment 1 (use methylene chloride as reaction dissolvent in the case where)1The spectrogram of H-NMR spectrum.
Formula (2a) compound represented obtained in [Fig. 3] embodiment 1 (use acetonitrile as reaction dissolvent in the case where)1The spectrogram of H-NMR spectrum.
Formula (1a) compound represented obtained in [Fig. 4] embodiment 1 (use hydrogen peroxide as oxidant in the case where)1The spectrogram of H-NMR spectrum.
Formula (1a) compound represented obtained in [Fig. 5] embodiment 1 (use metachloroperbenzoic acid as oxidant in the case where)1The spectrogram of H-NMR spectrum.
Formula (4a) compound represented obtained in [Fig. 6] embodiment 11The spectrogram of H-NMR spectrum.
Specific embodiment
<formula (1) compound represented>
Cycloaliphatic epoxy of the invention is following formula (1) compound represented (cycloaliphatic epoxy with sulfonic acid halide or sulfenyl halogen position).In formula (1), R1、R2、R3And R4It is identical or different, indicate hydrogen atom, halogen atom, the alkyl of the optionally carbon atom number 1~6 with halogen atom or optionally hydroxyl (hydroxylic moiety) by protecting group protection and the hydroxy alkyl of the optionally carbon atom number 1~6 with halogen atom.In formula (1), R5、R6And R7It is identical or different, indicate hydrogen atom, halogen atom, optionally with the alkyl of carbon atom number 1~6, the carboxyl of optional forming salt, substituted oxy carbonyl, the sulfino of optional forming salt, substituted oxy sulfinyl, the sulfo group of optional forming salt, substituted oxy sulfonyl or the cyano of halogen atom.Q indicates alkyl-substituted methylene, oxygen atom or the sulphur atom optionally by 1 or 2 carbon atom number 1~3.N indicates 1 or 2.
[chemical formula 7]
As above-mentioned halogen atom, it can be mentioned, for example: fluorine atom, chlorine atom, bromine atom etc..As the alkyl of carbon atom number 1~6, it can be mentioned, for example: methyl, ethyl, propyl, isopropyl, butyl, isobutyl group, sec-butyl, tert-butyl, amyl, hexyl etc..Wherein, the preferably alkyl of carbon atom number 1~3, more preferable methyl.As the alkyl of the carbon atom number 1~6 with halogen atom, it can be mentioned, for example: the chloros alkyl such as chloromethyl；Trifluoromethyl, 2, fluoro-alkyls such as 2,2- trifluoroethyls, pentafluoroethyl group (the preferably fluoro-alkyl of carbon atom number 1~3) etc..
As the hydroxy alkyl of carbon atom number 1~6, it can be mentioned, for example: hydroxymethyl, 2- hydroxyethyl, 1- hydroxyethyl, 3- hydroxypropyl, 2- hydroxypropyl, 4- hydroxybutyl, 6- hydroxyl hexyl etc..As the hydroxy alkyl of the carbon atom number 1~6 with halogen atom, it can be mentioned, for example: difluoro hydroxymethyl, the fluoro- 2- hydroxyethyl of 1,1- bis-, the fluoro- 2- hydroxyethyl of 2,2- bis-, 1,1,2,2- tetra- fluoro- 2- hydroxyethyl etc..Optionally having Have in the hydroxy alkyl of carbon atom number 1~6 of halogen atom, preferably the carbon atom number hydroxy alkyl or hydroxyhalogenalkyl that are 1 or 2 (especially carbon atom number is 1).The protecting group of the hydroxyl of hydroxy alkyl as the carbon atom number 1~6 optionally with halogen atom; it can enumerate and be often used as the protecting group of the protecting group of hydroxyl in organic synthesis field, such as: the group of ether or acetal bonds can be collectively formed in methyl, methoxy etc. with the oxygen atom for constituting hydroxyl；The group etc. of ester bond can be collectively formed in acetyl group, benzoyl etc. with the oxygen atom for constituting hydroxyl.As carboxyl, sulfino, sulfo group salt, alkali metal salt, alkali salt, transition metal salt etc. can be enumerated.
As above-mentioned substituted oxy carbonyl, it can be mentioned, for example: the alkoxy carbonyls such as methoxycarbonyl, ethoxy carbonyl, isopropyloxycarbonyl group, propoxycarbonyl (C1-4Alkoxy-carbonyl etc.)；The allyloxycarbonyls such as ethylene oxy carbonyl, allyloxy carbonyl (C2-4Alkenyloxy group-carbonyl etc.)；The cycloalkyloxycarbonyls such as cyclohexyl Epoxide carbonyl；Aryloxycarbonyls such as phenyloxycarbonyl etc..As substituted oxy sulfinyl, substituted oxy sulfonyl, it can be mentioned, for example: substituted oxy sulfinyl corresponding with above-mentioned substituted oxy carbonyl, substituted oxy sulfonyl.In Q, as the alkyl for the carbon atom number 1~3 being optionally substituted on methylene, it can be mentioned, for example: methyl, ethyl, propyl etc..As by the alkyl substituted methylene of 1 or 2 carbon atom number 1~3, it can be mentioned, for example: methylmethylene, dimethylmethylene etc..
As R1、R2、R3And R4, they are identical or different, preferably indicate: hydrogen atom；The alkyl or halogenated alkyl of the carbon atom numbers such as methyl, trifluoromethyl 1~3；Hydroxy alkyl or hydroxyhalogenalkyl (especially the hydroxyls such as hydroxymethyl, acetoxy-methyl protected by protecting group hydroxymethyl) of the carbon atom number 1~3 that hydroxyl is optionally protected by protecting group etc., more preferably hydrogen atom.As R5、R6And R7, they are identical or different, preferably indicate: hydrogen atom；The alkyl or halogenated alkyl (especially methyl, halogenated methyl) of the carbon atom numbers such as methyl, trifluoromethyl 1~3；Substituted oxy carbonyl；Cyano, more preferably hydrogen atom.In addition, as n, preferably 2, as Q, preferably methylene.
In formula (1), X indicates halogen atom.As halogen atom, it can be mentioned, for example: fluorine atom, chlorine atom, bromine atom etc..
R in formula (1)1、R2It is optionally introversive or export-oriented with the position of epoxy group spatially.In addition, the R in formula (1)7With S (O)nThe position of X base spatially is optionally introversive or export-oriented.
As the typical example of formula (1) compound represented, compound shown in following formula can be enumerated (comprising each stereoisomer).It should be noted that X and n are respectively indicated and formula (1) identical meaning in following formula.In following formula, Ac indicates acetyl group.
[chemical formula 8]
[chemical formula 9]
[chemical formula 10]
The manufacturing method of cycloaliphatic epoxy of the invention is not particularly limited, such as, it can be by being handled using oxidant following formula (2) compound represented (ester ring type olefin(e) compound), to generate cycloaliphatic epoxy of the invention.
[chemical formula 11]
In formula (2), R1、R2、R3、R4、R5、R6、R7, Q, n and X it is identical as the meaning in formula (1) respectively (respectively with the R in formula (1)1、R2、R3、R4、R5、R6、R7, Q, n and X it is corresponding).In formula (2) compound represented, R1、R2Position spatially, R7With S (O)nThe position of X base spatially is optionally introversive or export-oriented respectively.
Formula (2) compound represented can be manufactured by known or customary way, be not particularly limited, for example, It can as shown below, by manufacturing following formula (ii) compound represented (unsaturated sulfonic acid halide or unsaturated sulfenyl halogen) and carrying out Diels-Alder reaction with following formula (iii) compound represented (cyclopentadiene derivant, furan derivatives or thiophene derivant).
[chemical formula 12]
R in formula (ii)5、R6、R7, n and X it is identical as the meaning in formula (1) respectively (respectively with the R in formula (1)5、R6、R7, n and X it is corresponding).In addition, the R in formula (iii)1、R2、R3、R4And Q it is identical as the meaning in formula (1) respectively (respectively with the R in formula (1)1、R2、R3、R4And Q is corresponding).
As formula (ii) compound represented, it can be mentioned, for example: the halide of the unsaturated sulfonic acids such as vinyl sulfonic acid, Alpha-Methyl vinyl sulfonic acid, Beta-methyl vinyl sulfonic acid, α-trifluoromethyl vinyl sulfonic acid, β-trifluoromethyl vinyl sulfonic acid, alpha-cyano vinyl sulfonic acid, beta-cyano vinyl sulfonic acid, α-carboxy vinyl sulfonic acid, β-carboxy vinyl sulfonic acid；The halide etc. of unsaturation sulfinic acid corresponding with these compounds.As formula (iii) compound represented, it can be mentioned, for example: 1, 3- cyclopentadiene, 1- methyl-1, 3- cyclopentadiene, 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, bis- (hydroxymethyls) -1 of 4-, 3- cyclopentadiene, 2, bis- (hydroxymethyls) -1 of 3-, 3- cyclopentadiene, 1- acetoxy-methyl -1, 3- cyclopentadiene, 1, 4- bis- (acetoxy-methyls) Cyclopentadiene derivants (the Q=CH such as bis- (acetoxy-methyl) -1,3- cyclopentadiene of -1,3- cyclopentadiene, 2,3-2Compound)；Furans, 2- methylfuran, 3- methylfuran, 2,5- dimethyl furan, 3,4- dimethyl furan, 2,3,4, the furan derivatives (compound of Q=O) such as bis- (hydroxymethyl) furans of 5- 4-methyl furan, 2- hydroxymethylfurans, 2,5-, 2- acetoxy-methyl furans, bis- (acetoxy-methyl) furans of 2,5-；Thiophene derivant (compound of Q=S) corresponding with above-mentioned furan derivatives etc..
Reacting for formula (ii) compound represented and formula (iii) compound represented can carry out in the presence of the solvent or in the presence of non-.As solvent, it can be mentioned, for example: the esters such as ethyl acetate；The organic acids such as acetic acid；The alcohol such as the tert-butyl alcohol；The halogenated hydrocarbons such as chloroform, methylene chloride, 1,2- dichloroethanes；The aromatic hydrocarbons such as benzene；Hexane, The aliphatic hydrocarbons such as heptane, octane；The ester ring type hydrocarbons such as hexamethylene；The amides such as n,N-Dimethylformamide, n,N-dimethylacetamide；The nitriles such as acetonitrile, propionitrile, benzonitrile；The chains or cyclic ether etc. such as ether, tetrahydrofuran (THF).Solvent can be used alone, and can also be used in combination of two or more.
In above-mentioned reaction, in order to improve reaction speed, the selectivity of reaction (stereoselectivity etc.), lewis acid can be added in system.As lewis acid, it is not particularly limited, it can be mentioned, for example: AlCl3、SnCl4、TiCl4、BF3、ZnI2Deng.The temperature (reaction temperature) for carrying out above-mentioned reaction can suitably be selected according to type of reaction raw materials etc., be not particularly limited, but preferably -80~300 DEG C, more preferably -70~250 DEG C.In general, above-mentioned reaction carries out under normal pressure or pressurization.In addition, above-mentioned reaction can be carried out according to the arbitrary form in batch-type, semi-batch, continous way etc..Formula (2) compound represented generated through above-mentioned reaction can be isolated and purified for example, by separation methods such as filtering, concentration, distillation, extraction, partial crystallization, recrystallization, column chromatographies or by separation method that these methods are composed.
It should be noted that above-mentioned formula (ii) compound represented can be manufactured by known or customary way, it is not particularly limited, for example, can be manufactured as shown below by the de-hydrogen halide of following formula (i) compound represented.
[chemical formula 13]
R in formula (i)5、R6、R7, n and X it is identical as the meaning in formula (1) respectively (respectively with the R in formula (1)5、R6、R7, n and X it is corresponding).Y in formula (i) indicates halogen atom, and it can be mentioned, for example chlorine atom, bromine atom, iodine atoms etc..Above-mentioned reaction (de-hydrogen halide) can use known customary way and implement, and be not particularly limited, for example, can be according to Japanese Unexamined Patent Publication 2010-83873 bulletin, J.Am.Chem.Soc., method disclosed in 1954,76,1926 etc. is implemented.
As the oxidant (oxidant for being handled formula (2) compound represented) reacted with formula (2) compound represented, known or usual oxidant can be used, it is not particularly limited, it can be mentioned, for example: peroxide (especially hydrogen peroxide) or peracid (the especially peracid as derived from hydrogen peroxide, for example, the aftermentioned balance peracid etc. for having used hydrogen peroxide) etc..As above-mentioned peroxide, it can be mentioned, for example: hydrogen peroxide, peroxide, hydroperoxides, peroxy acid, salt of peroxy acid etc..As hydrogen peroxide, also pure hydrogen peroxide can be used, but from the aspect of operability, (for example, form of the aqueous hydrogen peroxide solution of 30 weight % or so) is used usually in the form of diluted in solvent appropriate (such as water). The usage amount of the peroxide such as the hydrogen peroxide in above-mentioned reaction (formula (2) compound represented is reacted with oxidant) is not particularly limited, relative to 1 mole of compound represented of formula (2), preferably 0.9~5 mole, more preferably 0.9~3 mole, further preferably 0.95~2 mole.
As above-mentioned peracid, it can be mentioned, for example: the organic peracids such as performic acid, peracetic acid, perpropionic acid, trifluoroperacetic acid, benzylhydroperoxide, metachloroperbenzoic acid, single peroxide phthalic acid；Inorganic peracids such as permanganic acid etc..Peracid can also be used in the form of salt.Organic peracid is also possible to balance peracid (for example, balance performic acid, equilibrium peracetic acid etc.).That is, making them generate corresponding organic peracid in system such as that organic acid formic acid, acetic acid and hydrogen peroxide can be applied in combination.In the case where using balance peracid, as catalyst, the strong acid such as a small amount of sulfuric acid can be added.The usage amount of peracid in above-mentioned reaction (formula (2) compound represented is reacted with oxidant) is not particularly limited, relative to 1 mole of compound represented of formula (2), preferably 0.8~2 mole, more preferably 0.9~1.5 mole, further preferably 0.95~1.2 mole.
Above-mentioned hydrogen peroxide is mostly used in conjunction with metallic compound.As above-mentioned metallic compound, it can be mentioned, for example: oxide, oxyacid or its salt, sulfide, halide, oxyhalide, boride, carbide, silicide, nitride, phosphide, peroxide, complex compound (inorganic complex and organic complex), organo-metallic compound comprising metallic elements such as W, Mo, V, Mn, Re etc..These metallic compounds can be used alone, and can also be used in combination of two or more.
As above-mentioned oxide, it can be mentioned, for example: tungsten oxide (WO2、WO3Deng)；Molybdenum oxide (MoO2、MoO3Deng)；Vanadium oxide (VO, V2O3、VO2、V2O5Deng)；Manganese oxide (MnO, Mn2O3、Mn3O4、MnO2、Mn2O7Deng)；Composite oxides etc. comprising metallic elements such as W, Mo, V, Mn.
It as above-mentioned oxyacid, other than such as wolframic acid, molybdic acid, vanadic acid, mangaic acid etc., can also enumerate: with more wolframic acids, isopolymolybdic acid, with isopolyacids such as more vanadic acid；The heteropoly acid etc. that phosphotungstic acid, silico-tungstic acid, phosphomolybdic acid, silicomolybdic acid, molybdovanaphosphoric acid etc. are made of above-mentioned metallic element and other elements etc..As other elements etc. in above-mentioned heteropoly acid, preferably phosphorus or silicon, more preferably phosphorus.
As the salt of above-mentioned oxyacid, it can be mentioned, for example: the alkali metal salts such as sodium salt, sylvite of above-mentioned oxyacid；The alkali salts such as magnesium salts, calcium salt, barium salt；Ammonium salt；Transition metal salt etc..A part that the salt (for example, salt of heteropoly acid) of oxyacid is also possible to will be equivalent to the hydrogen atom of cation replaces with salt made of other cations.
As the peroxide comprising metallic element, it can be mentioned, for example: the peroxy acids such as peroxide wolframic acid, peroxo-polymolybdic acid, peroxide vanadic acid；The salt of the peroxy acids such as alkali metal salt, alkali salt, ammonium salt, the transition metal salt of above-mentioned peroxy acid；The peracid such as permanganic acid；The alkali metal salt of above-mentioned peracid, alkali salt, ammonium salt, The salt etc. of the peracid such as transition metal salt.
The usage amount for the metallic compound being used in conjunction with above-mentioned hydrogen peroxide is not particularly limited, but preferably with respect to 1 mole of compound represented of formula (2) is 0.0001~2 mole, more preferably 0.0005~0.5 mole, further preferably 0.001~0.2 mole.
Reacting for formula (2) compound represented and oxidant can carry out in the presence of the solvent or in the presence of non-.As solvent, known or usual solvent can be used, be not particularly limited, can enumerate: the alcohol such as tert-butyl alcohol；The halogenated hydrocarbons such as chloroform, methylene chloride, 1,2- dichloroethanes；The aromatic hydrocarbons such as benzene；The aliphatic hydrocarbons such as hexane, heptane, octane；The ester ring type hydrocarbons such as hexamethylene；The amides such as n,N-Dimethylformamide, n,N-dimethylacetamide；The nitriles such as acetonitrile, propionitrile, benzonitrile；The chains such as ether, tetrahydrofuran or cyclic ether；The esters such as ethyl acetate；The organic acids such as acetic acid；Water etc..Solvent can be used alone, and can also be used in combination of two or more.In addition, reaction can carry out in homogeneous system in the case where using solvent, can also be carried out in heterogeneous system, two-phase system.It should be noted that using water or the solvent comprising water as solvent in the case where reaction in heterogeneous system more.
Formula (2) compound represented is considered that reaction speed and reaction selectivity etc. with the temperature (reaction temperature) when oxidant reaction and suitably selects, and is not particularly limited, but preferably 0~100 DEG C, more preferably 10~80 DEG C.Above-mentioned reaction can be carried out according to the arbitrary form in batch-type, semi-batch, continous way etc., also the same for the other reactions recorded in this manual.
By above-mentioned reaction, epoxidation, production (1) compound represented (cycloaliphatic epoxy of the invention) occur for carbon-to-carbon double bond possessed by formula (2) compound represented.Formula (1) compound represented generated by above-mentioned reaction can be for example, by known in the separation methods such as filtering, concentration, distillation, extraction, partial crystallization, recrystallization, column chromatography or the separation method being composed of these methods etc. or usual purification process is isolated and purified.
Cycloaliphatic epoxy (formula (1) compound represented) of the invention is used as coating, the raw material of functional high-polymer, medicine, pesticide and raw material of other fine chemicals etc..In particular, following formula (4) compound represented (2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 of cycloaliphatic epoxy of the invention particularly preferable as the raw material for being used as the raw material of coating, functional high-polymer, medicine, pesticide and other fine chemicals3,7] nonane derivatives) and raw material use.By using cycloaliphatic epoxy of the invention as raw material, method manufacture formula (4) compound represented that industrially can securely and effectively implement can use.
[chemical formula 14]
In formula (4), R1、R2、R3、R4、R5、R6、R7, Q and n it is identical as the meaning in formula (1) (respectively with the R in formula (1)1、R2、R3、R4、R5、R6、R7, Q and n it is corresponding).It should be noted that R1Position spatially with hydroxyl is optionally introversive or export-oriented.
<manufacturing method of formula (4) compound represented>
Use cycloaliphatic epoxy of the invention as formula (4) compound represented (2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 of raw material3,7] nonane derivatives) and manufacturing method (also referred to as " the manufacturing method of the present invention "), it is that formula (1) compound represented (cycloaliphatic epoxy of the invention) hydrolysis is obtained into following formula (3) compound represented (cycloaliphatic epoxy), cyclization, the method for production (4) compound represented are carried out again.
[chemical formula 15]
In formula (3), R1、R2、R3、R4、R5、R6、R7, Q and n it is identical as the meaning in formula (1) (that is, formula (4)) (respectively with the R in formula (1)1、R2、R3、R4、R5、R6、R7, Q and n it is corresponding).In formula (3), M indicates hydrogen atom, alkali metal, alkaline-earth metal or quaternary ammonium group.It should be noted that R1、R2With the position spatially of epoxy group, R7With S (O)nThe position spatially of OM base is optionally introversive or export-oriented respectively.
As the alkali metal of M, it can be mentioned, for example sodium, potassium etc..As the alkaline-earth metal of M, it can be mentioned, for example magnesium, calcium, barium etc..As the quaternary ammonium group of M, it can be mentioned, for example the groups that: the nitrogen-atoms in aftermentioned tertiary amines, nitrogen-containing aromatic compound is cationized (for example, based on protonation, alkylated cationization) and is formed (for example, NH4 +；Me3NH+、Et3NH+Equal tertiary alkyls ammonium ion；Pyridinium ion etc.) etc..
The method that the hydrolysis of formula (1) compound represented obtains formula (3) compound represented is not particularly limited, can be used can be by the S (O) in formula (1)nX base is converted to S (O)nThe known usual method for hydrolysis of OM base.As the method for hydrolysis, it can be mentioned, for example: the method that is hydrolyzed in the presence of acids and bases, there is no methods being hydrolyzed in the case where acid and alkali etc..Wherein, from the viewpoint of reaction speed and yield, the method that is preferably hydrolyzed in the presence of base.
In the hydrolysis of the compound shown in formula (1), known or usual alkali can be used, be not particularly limited, it can be mentioned, for example: the hydroxide of the alkali metal such as lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide；The hydroxide of the alkaline-earth metal such as magnesium hydroxide, calcium hydroxide, barium hydroxide；The carbonate of the alkali metal such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate；The carbonate of the alkaline-earth metal such as magnesium carbonate；The bicarbonate of the alkali metal such as lithium bicarbonate, sodium bicarbonate, sodium bicarbonate, saleratus, caesium bicarbonate；The acylate (for example, acetate) of the alkali metal such as lithium acetate, sodium acetate, potassium acetate, cesium acetate；The acylate (for example, acetate) of the alkaline-earth metal such as magnesium acetate；The alkali alcoholates such as lithium methoxide, sodium methoxide, sodium ethoxide, sodium isopropylate, potassium ethoxide, potassium tert-butoxide；The alkali phenolates such as phenol sodium；Ammonia；Chain fatty race tertiary amine [such as, trimethylamine, triethylamine, tripropyl amine (TPA), tri-n-butylamine, diisopropyl ethyl amine etc.], annular aliphatic tertiary amine [such as, N- crassitude, N- methyl piperidine, N-methylmorpholine, 1,4- diazabicyclo [2.2.2] octane, 1,5- diazabicyclo [4.3.0] nonane -5- alkene, 1,11 carbon -7- alkene of 8- diazabicyclo [5.4.0] etc.], the amines such as aromatic nitrile base [for example, n,N-Dimethylaniline etc.]；Azole derivatives [such as, pyrroles, N- methylpyrrole etc.], imdazole derivatives [such as, imidazoles, 1- methylimidazole, 2-methylimidazole, 4-methylimidazole etc.], triazole derivative [such as, triazole etc.], pyridine derivate [such as, pyridine, 4- (dimethylamino) pyridine, 2- picoline, 3- picoline, 4- picoline, 2, 4- lutidines, 2, 6- lutidines, 3, 4- lutidines, 3, 5- lutidines, 2- methoxypyridine, 2- cyanopyridine, nicotinonitrile, 4- cyanopyridine, bipyridyl, trimethylpyridine, quinoline, isoquinolin etc.], pyridyl derivatives [such as, pyridazine, 3- methyl pyridazine, 4- methyl pyridazine etc.], pyrimidine derivatives [such as, pyrimidine, 4- methylpyrimidine etc.], pyrazine is derivative Nitrogen-containing aromatic compounds such as object [for example, pyrazine, 2- methylpyrazine etc.], pyrrolotriazine derivatives [for example, triazine etc.] (nitrogenous heteroaromatic formula compound) etc..Alkali can be used alone, and can also be used in combination of two or more.In addition, alkali can also be used in the form of being dissolved or dispersed in water equal solvent.The usage amount of alkali is not particularly limited, but preferably with respect to 1 mole of compound represented of formula (1) is 1~10 mole, more preferably 1~5 mole.
In the hydrolysis of formula (1) compound represented, known or usual acid can be used, be not particularly limited, it can be mentioned, for example: the inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid；Phosphate；The carboxylic acids such as acetic acid, formic acid, trifluoroacetic acid；The sulfonic acid such as methanesulfonic acid, trifluoromethanesulfonic acid, p-methyl benzenesulfonic acid；Atlapulgite Equal solid acids；Lewis acids such as iron chloride etc..Acid can be used alone, and can also be used in combination of two or more.In addition, acid can also be used in the form of being dissolved or dispersed in water equal solvent.The usage amount of acid is not particularly limited, but preferably with respect to 1 mole of compound represented of formula (1) is 1~10 mole, more preferably 1~5 mole.
Above-mentioned reaction (hydrolysis of formula (1) compound represented) can carry out in the presence of the solvent or in the presence of non-.As solvent, known or usual solvent can be used, be not particularly limited, may be used at solvent used in the reacting of above-mentioned formula (2) compound represented and oxidant etc..In addition, the reaction system of above-mentioned reaction can be mixed by organic layer and water layer and reach uniform, without mixing but heterogeneous system, two-phase system can also be become.For matrix (for example, formula (1) compound represented, acid, alkali etc.), the degree that in solvent reaction can extremely carry out is dissolved them in, solution state is can be, is also possible to dispersity.Furthermore it is also possible to be used as solvent to use in water itself.Solvent can be used alone, and can also be used in combination of two or more.
The amount of water used in above-mentioned reaction is not particularly limited, but preferably with respect to 1 mole of compound represented of formula (1) is 1~1000 mole, more preferably 1~100 mole.
The temperature (reaction temperature) for carrying out above-mentioned reaction is not particularly limited, but preferably 0~100 DEG C, more preferably 10~50 DEG C.The time (reaction time) for carrying out above-mentioned reaction is not particularly limited, such as can suitably select from 0.01~100 hour range.
As long as carrying out method formula (1) compound represented of above-mentioned reaction and embodiment that water coexists (embodiment of acid or alkali (especially alkali) preferably further also coexists), it is not particularly limited.It can be mentioned, for example: into formula (1) compound represented or its solution add water (such as, dissolved with acid or alkali aqueous solution) method, Xiang Shui (for example, dissolved with acid or alkali aqueous solution) in adding type (1) compound represented or the method for its solution etc..
It should be noted that, formula (3) compound represented generated through above-mentioned reaction can directly (without purifying), supply to subsequent reactions (reaction of production (4) compound represented), can also be supplied after being purified to subsequent reactions.As purification process, known or customary way can be used, be not particularly limited, it can be mentioned, for example the separation methods such as filtering, concentration, distillation, extraction, partial crystallization, recrystallization, column chromatography or the separation methods etc. being composed of these methods.
Then, formula (3) compound represented (cycloaliphatic epoxy) carries out cyclization and production (4) compound represented.In the case where M is hydrogen atom, above-mentioned cyclization for example can be only dissolved in solvent by formula (3) compound represented to carry out.On the other hand, in the case that M is alkali metal, alkaline-earth metal or quaternary ammonium group, as the method for carrying out above-mentioned cyclization, the presence in acid can be enumerated Descend the method heated as needed.
As above-mentioned acid, known or usual acid can be used, be not particularly limited, it can be mentioned, for example: the inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid；Phosphate；The carboxylic acids such as acetic acid, formic acid, trifluoroacetic acid；The sulfonic acid such as methanesulfonic acid, trifluoromethanesulfonic acid, p-methyl benzenesulfonic acid；The solid acids such as atlapulgite；Lewis acids such as iron chloride etc..It should be noted that acid can be used alone, can also be used in combination of two or more.In addition, acid can also be used in the form of being dissolved or dispersed in water equal solvent.
Above-mentioned reaction (cyclization of formula (3) compound represented) can carry out in the presence of the solvent or in the presence of non-.As solvent, known or usual solvent can be used, be not particularly limited, may be used at solvent used in the reacting of above-mentioned formula (2) compound represented and oxidant etc..Furthermore it is also possible to be used as solvent to use in water itself.Solvent can be used alone, and can also be used in combination of two or more.
The temperature (reaction temperature) for carrying out above-mentioned reaction is not particularly limited, but preferably 10~100 DEG C, more preferably 20~80 DEG C.The time (reaction time) for carrying out above-mentioned reaction is not particularly limited, but preferably 1~40 hour, more preferably 5~30 hours.
Formula (4) compound represented (2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 generated through above-mentioned reaction3,7] nonane derivatives) can be for example, by known in the separation methods such as filtering, concentration, distillation, extraction, partial crystallization, recrystallization, column chromatography or the separation method being composed of these methods etc. or usual means of purification is isolated and purified.
It should be noted that the cyclization of compound shown in the hydrolysis and formula (3) of compound shown in formula (1) in the manufacturing method of the present invention can be carried out continuously, discontinuous can also carry out.
The manufacturing method of the present invention can also further include production (1) compound represented process (such as, the process that above-mentioned formula (2) compound represented is handled using oxidant), other process (for example, process for generating above-mentioned formula (2) compound represented etc.).These processes and it is above-mentioned reaction is hydrolyzed, the process of cyclization can be carried out continuously, discontinuous can also carry out.
Manufacturing method according to the invention can use industrial safe and efficient method manufacture formula (4) compound represented.Specifically, there are the hidden danger that N- oxide of by-product pyridines etc. has volatile compound unlike for example not via the method recorded in Japan Patent 5352387 of formula (1) compound represented for the manufacturing method of the present invention, and can be with high yield production (4) compound represented.
The raw material of formula (4) compound represented that manufacturing method through the invention obtains preferably as such as raw material of coating, functional high-polymer, medicine, pesticide and other fine chemicals etc. uses.For example, by importing polymerizable group (for example, acryloyl group, methylacryloyl etc.) to the hydroxylic moiety of compound shown in formula (4), it is available to keep resistance to chemical reagents etc. in the case where being derived as polymer etc. Dissolubility relative to water, the 4- oxygen -5- thia tricyclic [4.2.1.0 useful as the monomer component of high functionality macromolecule etc. etc. after water-disintegrable and hydrolysis are improved while stability3,7] nonane derivatives.Polymerizable group is not particularly limited to the importing of formula (4) compound represented, can be carried out according to method recorded in such as Japanese Unexamined Patent Publication 2007-31355 bulletin etc..
Embodiment
Hereinafter, the present invention is described in more detail, but the present invention is not limited to these embodiments in conjunction with the embodiments.It should be noted that the identification of product passes through1H-NMR spectrum measurement (solvent: CDCl3) Lai Jinhang.
Embodiment 1
Formula (1a) compound represented has been manufactured according to following reaction route figures.In addition, having manufactured formula (4a) compound represented by raw material of formula (1a) compound represented.
[chemical formula 16]
[step 1: the synthesis of compound shown in formula (iia)]
Adding type (ia) compound represented (purity 98%, 20.00g, 120.23mmol) and methylene chloride (100ml), are cooled to -5 DEG C in the three-neck flask equipped with the inner capacities 500ml of blender, thermometer and dropping funel while being stirred.Then, it is added thereto in a manner of not making interior temperature be more than 0 DEG C of speed, being added dropwise through 30 minutes or more and 2,6- lutidines (purity 98%, 14.46g, 1.1 equivalents) is dissolved in solution made of methylene chloride (100ml).On one side by gained mixture natural warming to room temperature, continue stirring 40 minutes on one side.Then, it is cooled to after 0 DEG C, is slowly added to then stir mixture 2 minutes under synthermal (0 DEG C) by ice-cold sulfuric acid (1%, 125ml).Then, dichloromethane layer is isolated, using water washing 2 times of 100ml, and is dried, is concentrated with sodium sulphate, has been obtained shallow The product (14.69g, yield 96%) of the form of the oil of brown.By the product1H-NMR composes measurement result it has been confirmed that generating formula (iia) compound represented (referring to Fig. 1).
It should be noted that the reaction about step 1, the method by being different from above-mentioned reaction route figure, specifically, can similarly implement in the case where using ethyl acetate as solvent as described below.
[step 1 (other way): using ethyl acetate as solvent]
Adding type (ia) compound represented (purity 98%, 20.00g, 120.23mmol) and ethyl acetate (200ml), are cooled to -5 DEG C in the three-neck flask equipped with the inner capacities 500ml of blender, thermometer and dropping funel while being stirred.Then, it is added thereto in a manner of not making interior temperature be more than 0 DEG C of speed, being added dropwise through 30 minutes or more and 2,6- lutidines (purity 98%, 14.46g, 1.1 equivalents) is dissolved in solution made of ethyl acetate (100ml).At this point, white solid has been precipitated.On one side by gained mixture natural warming to room temperature, continue stirring 40 minutes on one side.Then, it is cooled to after 0 DEG C, is slowly added to then stir mixture 2 minutes under synthermal (0 DEG C) by ice-cold sulfuric acid (1%, 125ml).Then, ethyl acetate layer is isolated, with water washing 2 times of 100ml, and is dried, is concentrated with sodium sulphate, has obtained the product (13.64g, yield 90%) of the form of beige oil.By1The result of H-NMR spectrum measurement generates formula (iia) compound represented it has been confirmed that with using in the same manner as the case where methylene chloride is as solvent.
[step 2: the synthesis of compound shown in formula (2a)]
Cyclopentadiene (3.13g, 1.2 equivalents), phenthazine (39mg, 0.005 equivalent) and methylene chloride (50ml) are added in the three-neck flask equipped with the inner capacities 100ml of blender, thermometer and dropping funel, and -10 DEG C are cooled to while being stirred.Then, formula (iia) compound represented (5.00g, 39.51mmol) is added thereto in a manner of not making interior temperature be more than -5 DEG C of speed, be added dropwise through 1 hour or more and is dissolved in solution made of methylene chloride (10ml).After completion of dropwise addition, acquired solution is continued to stirring 3 hours in -10~-5 DEG C.Then, it is concentrated while decompression in 25~30 DEG C, has obtained the crude product (7.61g, quantitative, introversive/extroversion=9.09/1) of the form of the oil of pale orange.By the product1The result of H-NMR spectrum measurement is it has been confirmed that generate formula (2a) compound represented (referring to fig. 2).
It should be noted that formula (2a) compound represented is solidified in -10 DEG C.
It should be noted that the reaction about step 2, the method by being different from above-mentioned reaction route figure, specifically, can similarly implement in the case where using acetonitrile as solvent as described below.
[step 2 (other way): using acetonitrile as solvent]
Cyclopentadiene (0.63g, 1.2 equivalents), phenthazine (8mg, 0.005 equivalent) and acetonitrile (15ml) are added in the three-neck flask equipped with the inner capacities 100ml of blender, thermometer and dropping funel, are stirred - 10 DEG C are cooled to while mixing.Then, formula (iia) compound represented (1.00g, 7.90mmol) is added thereto in a manner of not making interior temperature be more than -5 DEG C of speed, be added dropwise through 1 hour or more and is dissolved in solution made of acetonitrile (10ml).After completion of dropwise addition, acquired solution is continued to stirring 3 hours in -10~-5 DEG C.Then, it is concentrated while decompression in 35~40 DEG C, has obtained the crude product (1.52g, quantitative, introversive/extroversion=10.7/1) of the form of the oil of pale orange.By the product1The result of H-NMR spectrum measurement is it has been confirmed that generate formula (2a) compound represented (referring to Fig. 3).
[step 3；The synthesis of formula (1a) compound represented]
Equipped with adding type (2a) compound represented (1.00g, 5.19mmol), formic acid (98%, 0.49g, 2.0 equivalents), oxalic acid (dehydration) (20mg, 0.03 equivalent) and acetonitrile (15ml) while stirring in the three-neck flask of blender and the inner capacities 100ml of thermometer.Then, it is added dropwise in 25 DEG C through 1 minute syringe utilized above and 30% aqueous hydrogen peroxide solution (0.88g, 1.5 equivalents) is added.Then, acquired solution is heated to 50 DEG C, stirred 18 hours.Then, reaction mixture is cooled to 5~10 DEG C, is slowly added to 10% sodium sulfite aqueous solution until can not detect peracid using potassium iodide starch test paper.For thus obtained product, used in the next steps without purifying.By the product1The result of H-NMR spectrum measurement is it has been confirmed that generate formula (1a) compound represented (bicyclic [2.2.1] heptane -2- alkene -5- sulfonic acid chloride of 2,3- epoxies) (referring to fig. 4).
It should be noted that the reaction about step 3, the method by being different from above-mentioned reaction route figure, specifically, can similarly implement in the case where using metachloroperbenzoic acid (mCPBA) as oxidant as described below.
[step 3 (other way): using mCPBA as oxidant]
Adding type (2a) compound represented (8.00g, 41.52mmol) and methylene chloride (60ml), are cooled to 0 DEG C in the three-neck flask equipped with the inner capacities 250ml of blender, dropping funel and thermometer while being stirred.Then, not make interior temperature be more than that 5 DEG C of speed is added dropwise and is added mCPBA (75%, 10.03g, 1.05 equivalents) being dissolved in solution made of methylene chloride (40ml).Then, acquired solution is heated up to 5~10 DEG C, be stirred until formula (2a) compound represented is totally consumed.It should be noted that the consumption of formula (2a) compound represented can be checked using TLC.Then, reaction mixture is cooled to 0 DEG C again, is slowly added to 10% sodium sulfite aqueous solution until can not detect peracid using potassium iodide starch test paper.Thereafter, for organic layer, 1 time (until reaching pH=7~8) is washed with 10% sodium bicarbonate aqueous solution, 1 time is washed with water (40ml), is washed 1 time with saline solution (40ml), and it is made it dry with sodium sulphate, it is concentrated, has obtained the crude product (8.3g) of the form of the oil of yellow.
Further the oil of 1.5g yellow is purified using silica gel chromatography (eluent: PE (petroleum ether)/ethyl acetate=10/1~5/1), has obtained the product (0.39g, yield 34%) of flavescent white solid forms.By the product1The result of H-NMR spectrum measurement is it has been confirmed that generate formula (1a) compound represented (bicyclic [2.2.1] heptane -2- alkene -5- sulfonic acid chloride of 2,3- epoxies) (referring to Fig. 5).
[step 4: the synthesis of compound shown in formula (3a)]
Adding type (1a) compound represented (2.00g, 9.58mmol) and THF (15ml) while stirring in the three-neck flask equipped with the inner capacities 100ml of blender, dropping funel and thermometer.Then, it was added dropwise in 25 DEG C through 3 minutes or more and sodium bicarbonate (2.01g, 2.5 equivalents) is dissolved in solution made of water (20ml).Then, gained suspension is stirred 1.5 hours in the temperature, is used in subsequent step 5 without purifying.
[step 5: the synthesis of compound shown in formula (4a)]
Equipped with side stirring addition suspension (suspension obtained in step 4) in the three-neck flask of blender and the inner capacities 100ml of thermometer.Then, it is added dropwise in 25 DEG C through 2 minutes syringes utilized above and formic acid (98%, 2.25g, 5.0 equivalents) is added.Then, gained suspension is heated to 50 DEG C, is stirred 18 hours in the temperature.THF is evaporated, dilutes residue using ethyl acetate (100ml).Thereafter, for organic layer, 1 time is washed with saturated sodium bicarbonate aqueous solution (30ml), 2 times are washed with water (20ml), is washed 1 time with saline solution (20ml), and it is made it dry using sodium sulphate, it is concentrated, has obtained the crude product (1.3g) of the form of colourless oil.
The crude product is recrystallized using Di Iso Propyl Ether (100ml), the pure product (0.8g) of white solid forms is obtained (wherein, it is analyzed according to TLC, show that there are a large amount of products in the filtrate of recrystallization, it is therefore desirable to optimize to the condition of recrystallization).By the product1The result of H-NMR spectrum measurement is it has been confirmed that generate formula (4a) compound represented (2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane -2,2- diketone) (referring to Fig. 6).
The continuous yield on the basis of compound shown in formula (ia) of compound shown in the formula as obtained from step 1~5 (4a) is 34%.It is possible thereby to confirm, manufacturing method according to the invention, it can use industrial safe and efficient method with good yield and manufacture 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane derivatives.
Embodiment 2
[2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 is continuously synthesized by formula (ia) compound represented3,7] nonane -2,2- diketone]
Feed type (ia) compound represented (50g) and methylene chloride into the three-neck flask of 500ml (150ml), is cooled to -5 DEG C.It is added dropwise thereto within 40 minutes in the way of not making up to 0 DEG C or more of liquid temperature rise and 2,6- lutidines (36.15g) is dissolved in solution made of methylene chloride (100ml).After completion of dropwise addition, while reaction temperature is slowly raised to 22 DEG C, continue stirring 1.5 hours.Then, reaction solution is cooled down, again not make liquid temperature be more than that sulfuric acid (1%, 250g) is added dropwise in 10 DEG C of speed.After completion of dropwise addition, water layer is removed, organic layer is washed 2 times with water (200mL).Using thus obtained reaction solution as " reaction of coarse liquid A ".So far, it is equivalent to above-mentioned step 1.
Cyclopentadiene (22.3g), phenthazine (305mg) and methylene chloride (100ml) are fed into the three-neck flask of other 1L, are cooled to -10 DEG C.Above-mentioned reaction of coarse liquid A is added dropwise thereto within 2 hours in a manner of not making liquid temperature be more than -5 DEG C.After completion of dropwise addition, in reaction temperature -10~-5 DEG C, the reaction was continued 4 hours.Using thus obtained reaction solution as " reaction of coarse liquid B ".It obtains after reaction of coarse liquid A so far, being equivalent to above-mentioned step 2.
Reaction of coarse liquid B is held in 5~10 DEG C, is added after 98% formic acid (34.57g), through 10 minutes 30% aqueous hydrogen peroxide solutions of dropwise addition (41.72g).After completion of dropwise addition, in 22 DEG C of reaction temperature, the reaction was continued 40 hours.Then, liquid temperature is cooled to 10 DEG C, 10% sodium sulfite aqueous solution (30ml) is added dropwise in a manner of making 10~15 DEG C of liquid temperature.It after completion of dropwise addition, is confirmed using potassium iodide starch test paper, there is no the remaining of peroxide in system.Using thus obtained reaction solution as " reaction of coarse liquid C ".It obtains after reaction of coarse liquid B so far, being equivalent to above-mentioned step 3.
Sodium hydroxide (47.85g) is dissolved in sodium hydrate aqueous solution obtained from water (300ml) to be added drop-wise within 25 minutes in above-mentioned reaction of coarse liquid C in 15 DEG C.After completion of dropwise addition, by water layer and organic layer liquid separation, and after washing organic layer with water (100ml), liquid separation water-yielding stratum simultaneously merges with previous water layer.Using thus obtained water layer as " reaction of coarse liquid D ".It obtains after reaction of coarse liquid C so far, being equivalent to above-mentioned step 4.
98% formic acid (53.3g) was added dropwise into reaction of coarse liquid D through 5 minutes in 15 DEG C of liquid temperature.The reaction mixture is warming up to 50 DEG C, continues stirring 18 hours.After reaction, reaction solution is cooled to room temperature, has carried out 2 extractions using ethyl acetate (150ml).Merge the ethyl acetate layer, 5% sodium hydrate aqueous solution of addition makes pH reach 7.Then organic layer is recycled, is concentrated, the 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 of the target of faint yellow solid form is resulted in3,7] nonane -2,2- diketone.Receipts amount is 19.8g, the continuous yield on the basis of formula (ia) compound represented is 34%, the purity on the basis of GC area is 92% or more.
Reference example
[2- methacryloxy -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane -2,2- diketone synthesis]
Using (4a) compound represented of formula obtained in embodiment 1 as raw material, the 4- oxygen -5- thia tricyclic [4.2.1.0 with polymerizable group has been synthesized according to following sequences3,7] nonane derivatives.
2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 is fed in the four-neck flask of 100ml3,7] nonane -2,2- diketone (5.0g), sulfuric acid (0.26g), methacrylic acid (22.63g), p-hydroxyanisole (メ ト キ ノ Application) (0.15g) and toluene (50.0g), are mounted with thermometer and Dean and Stark apparatus.The vacuum degree of adjustment system is heated to reflux it at 85 DEG C of liquid temperature, and the reaction was continued 12 hours.After reaction, after being washed with water (50g) to gained organic layer, 3 times similarly is washed with 8% sodium bicarbonate aqueous solution to organic layer, is washed with water 3 times.Then, concentration of organic layers brings it about partial crystallization and carrying out cooling after adding heptane 50g, has obtained the 2- methacryloxy -4- oxa- -5- thia tricyclic [4.2.1.0 as object3,7] nonane -2,2- diketone 4.4g.It is 99.2% using the purity that gas chromatography (GC) is measured, yield 65%.
Comparative example 1
[2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.03,7] nonane -2,2- diketone synthesis]
Use 2- chloroethene alkanesulphonyl chlorides 350g as initial substance, synthesizes 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 according to Japan Patent 5352387 reference examples 1 and the method for embodiment 13,7] nonane -2,2- diketone.Receipts amount is 51.8g, yield (the continuous yield on the basis of 2- chloroethene alkanesulphonyl chlorides) is 6.5%.
Industrial applicibility
The raw material that cycloaliphatic epoxy of the invention is especially suitable as being used as formula (4) compound represented of the raw material of coating, the raw material of functional high-polymer, medicine, pesticide and other fine chemicals uses.By using cycloaliphatic epoxy of the invention as raw material, formula (4) compound represented is manufactured using the method that industrially can securely and effectively implement.

Claims (7)

  1. Cycloaliphatic epoxy shown in following formula (1),
    [chemical formula 1]
    In formula (1),
    R1、R2、R3And R4Identical or different, the hydroxy alkyl of the carbon atom number 1~6 of halogen atom is protected and optionally had by protecting groups to expression hydrogen atom, halogen atom, the alkyl of the optionally carbon atom number 1~6 with halogen atom or optional hydroxyl,
    R5、R6And R7It is identical or different; indicate hydrogen atom, halogen atom, optionally with the alkyl of carbon atom number 1~6, the carboxyl of optional forming salt, substituted oxy carbonyl, the sulfino of optional forming salt, substituted oxy sulfinyl, the sulfo group of optional forming salt, substituted oxy sulfonyl or the cyano of halogen atom
    Q indicates alkyl-substituted methylene, oxygen atom or the sulphur atom optionally by 1 or 2 carbon atom number 1~3,
    N indicates 1 or 2,
    X indicates halogen atom,
    R1、R2With the position spatially of epoxy group, R7With S (O)nThe position spatially of X base is optionally introversive or export-oriented respectively.
  2. Cycloaliphatic epoxy according to claim 1, wherein
    Q is methylene,
    R1、R2、R3、R4、R5、R6And R7For hydrogen atom,
    N is 2.
  3. The manufacturing method of cycloaliphatic epoxy shown in following formula (1),
    [chemical formula 2]
    In formula (1),
    R1、R2、R3And R4Identical or different, the hydroxy alkyl of the carbon atom number 1~6 of halogen atom is protected and optionally had by protecting groups to expression hydrogen atom, halogen atom, the alkyl of the optionally carbon atom number 1~6 with halogen atom or optional hydroxyl,
    R5、R6And R7It is identical or different; indicate hydrogen atom, halogen atom, optionally with the alkyl of carbon atom number 1~6, the carboxyl of optional forming salt, substituted oxy carbonyl, the sulfino of optional forming salt, substituted oxy sulfinyl, the sulfo group of optional forming salt, substituted oxy sulfonyl or the cyano of halogen atom
    Q indicates alkyl-substituted methylene, oxygen atom or the sulphur atom optionally by 1 or 2 carbon atom number 1~3,
    N indicates 1 or 2,
    X indicates halogen atom,
    R1、R2With the position spatially of epoxy group, R7With S (O)nThe position spatially of X base is optionally introversive or export-oriented respectively,
    Wherein, this method comprises:
    Ester ring type olefin(e) compound shown in following formula (2) is handled using oxidant, generates cycloaliphatic epoxy shown in above-mentioned formula (1),
    [chemical formula 3]
    In formula (2),
    R1、R2、R3、R4、R5、R6、R7, Q, n and X it is identical as the meaning in formula (1),
    R1、R2Position spatially, R7With S (O)nThe position spatially of X base is optionally introversive or export-oriented respectively.
  4. The manufacturing method of cycloaliphatic epoxy according to claim 3, wherein oxidant is hydrogen peroxide or the peracid as derived from hydrogen peroxide.
  5. The manufacturing method of cycloaliphatic epoxy according to claim 3 or 4, wherein
    Q is methylene,
    R1、R2、R3、R4、R5、R6And R7For hydrogen atom,
    N is 2.
  6. 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 shown in following formula (4)3,7] nonane derivatives manufacturing method,
    [chemical formula 4]
    In formula (4),
    R1、R2、R3And R4Identical or different, the hydroxy alkyl of the carbon atom number 1~6 of halogen atom is protected and optionally had by protecting groups to expression hydrogen atom, halogen atom, the alkyl of the optionally carbon atom number 1~6 with halogen atom or optional hydroxyl,
    R5、R6And R7It is identical or different; indicate hydrogen atom, halogen atom, optionally with the alkyl of carbon atom number 1~6, the carboxyl of optional forming salt, substituted oxy carbonyl, the sulfino of optional forming salt, substituted oxy sulfinyl, the sulfo group of optional forming salt, substituted oxy sulfonyl or the cyano of halogen atom
    Q indicates alkyl-substituted methylene, oxygen atom or the sulphur atom optionally by 1 or 2 carbon atom number 1~3,
    N indicates 1 or 2,
    R1Position spatially with hydroxyl is optionally introversive or extroversion,
    Wherein, this method comprises:
    The hydrolysis of cycloaliphatic epoxy shown in following formula (1) is obtained into following formula (3) compound represented, then carries out cyclization, generates 2- hydroxyl -4- oxa- -5- thia tricyclic shown in above-mentioned formula (4) [4.2.1.03,7] nonane derivatives,
    [chemical formula 5]
    In formula (1),
    R1、R2、R3、R4、R5、R6、R7, Q and n it is identical as the meaning in formula (4),
    X indicates halogen atom,
    R1、R2With the position spatially of epoxy group, R7With S (O)nThe position spatially of X base is optionally introversive or export-oriented respectively,
    [chemical formula 6]
    In formula (3),
    R1、R2、R3、R4、R5、R6、R7, Q and n it is identical as the meaning in formula (4),
    M indicates hydrogen atom, alkali metal, alkaline-earth metal or quaternary ammonium group,
    R1、R2With the position spatially of epoxy group, R7With S (O)nThe position spatially of OM base is optionally introversive or export-oriented respectively.
  7. 2- hydroxyl -4- oxa- -5- thia tricyclic [4.2.1.0 according to claim 63,7] nonane derivatives manufacturing method, wherein
    Q is methylene,
    R1、R2、R3、R4、R5、R6And R7For hydrogen atom,
    N is 2.
CN201580072340.8A 2015-03-11 2015-03-11 Cycloaliphatic epoxy and its manufacture method and the ring [4.2.1.0 of 2 hydroxyl, 4 oxa-, 5 thia three3,7] nonane derivatives manufacture method Pending CN107207457A (en)

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JP2007119696A (en) * 2005-10-31 2007-05-17 Daicel Chem Ind Ltd Polymeric compound having alicyclic skeleton
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