WO2018159846A1 - PRODUCTION METHOD FOR α,β-UNSATURATED ACID ESTER OR α-HALOESTER - Google Patents

PRODUCTION METHOD FOR α,β-UNSATURATED ACID ESTER OR α-HALOESTER Download PDF

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WO2018159846A1
WO2018159846A1 PCT/JP2018/008169 JP2018008169W WO2018159846A1 WO 2018159846 A1 WO2018159846 A1 WO 2018159846A1 JP 2018008169 W JP2018008169 W JP 2018008169W WO 2018159846 A1 WO2018159846 A1 WO 2018159846A1
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formula
compound represented
group
organic base
compound
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PCT/JP2018/008169
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French (fr)
Japanese (ja)
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岡添　隆
稔 公山
貴史 川上
京子 野崎
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Ａｇｃ株式会社
国立大学法人東京大学
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Publication of WO2018159846A1 publication Critical patent/WO2018159846A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/22—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety
    • C07C69/24—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with monohydroxylic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
    • C07C69/533—Monocarboxylic acid esters having only one carbon-to-carbon double bond
    • C07C69/54—Acrylic acid esters; Methacrylic acid esters

Definitions

  • the present invention relates to a method for producing an ⁇ , ⁇ -unsaturated acid ester or an ⁇ -haloester.
  • Non-Patent Document 1 1,1,1-trichloro-2-methyl-2-propanol (TCMP) is obtained from acetone and chloroform, and then 2-methoxy-2-methylpropanoic acid is obtained from TCMP.
  • TCMP 1,1,1-trichloro-2-methyl-2-propanol
  • 2-methoxy-2-methylpropanoic acid is obtained from TCMP.
  • a method for obtaining the methyl ester and further obtaining the methyl methacrylate (MMA) by dealcoholization is disclosed.
  • the manufacturing method of MMA described in Non-Patent Document 1 is as steps A to D below.
  • Step A CH 3 C (O) CH 3 + CHCl 3 ⁇ C (CH 3 ) 2 (OH) (CCl 3 )
  • Step B C (CH 3) 2 (OH) (CCl 3) + 4KOH + CH 3 OH ⁇ C (CH 3) 2 (OCH 3) (COOK) + 3KCl + 3H 2 O
  • Step C C (CH 3) 2 (OCH 3) (COOK) + CH 3 OH ⁇ C (CH 3) 2 (OCH 3) (COOCH 3) + KOH
  • Step D C (CH 3 ) 2 (OCH 3 ) (COOCH 3 ) ⁇ CH 2 ⁇ C (CH 3 ) C (O) OCH 3 + CH 3 OH
  • Patent Document 1 discloses a method of obtaining MMA by reacting TCMP and the like in the presence of zinc chloride to obtain a reaction crude liquid and then reacting the reaction crude liquid with methanol (Example 3).
  • Patent Document 2 discloses a method of obtaining MMA by reacting TCMP with methanol in the presence of zinc oxide (Example 1).
  • Non-Patent Document 1 Since the MMA production method described in Non-Patent Document 1 is performed in a multistage reaction, it is not economical from the viewpoints of process complexity and production cost.
  • the MMA manufacturing methods described in Patent Documents 1 and 2 use TCMP manufactured in advance. Therefore, when TCMP production is included in MMA production, it can be said that MMA is substantially produced by a multi-step reaction, and therefore there is room for improvement from an economical viewpoint.
  • ⁇ , ⁇ -unsaturated acid esters are conventionally produced by a reaction that requires a multi-step process, and it has been difficult to produce a short process, preferably in one pot.
  • the present invention has been made in view of the above problems, and an object of the present invention is to provide a production method for obtaining an ⁇ , ⁇ -unsaturated acid ester or ⁇ -haloester in a short process (preferably 1 pot).
  • a compound represented by formula (1), formula (2) and formula (3) described below in the presence of an organic base containing a nitrogen atom.
  • a compound represented by formula (4) described later ⁇ , ⁇ -unsaturated ester
  • a compound represented by formula (5) described later ⁇ -haloester
  • the present invention has been found. That is, the present inventor has found that the above problem can be solved by the following configuration. [1] A compound represented by the following formula (1), a compound represented by the following formula (2), and a compound represented by the following formula (3) are reacted in the presence of an organic base containing a nitrogen atom.
  • Formula (1) CH 3 C (O) R Formula (2) CHX 3 Formula (3)
  • CH 3 CXRC (O) OQ The symbols in the formula represent the following meanings.
  • R represents an alkyl group or aryl group having 1 to 10 carbon atoms, an alkyl group or aryl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom.
  • X represents a halogen atom.
  • Q represents a monovalent organic group having 1 to 20 carbon atoms.
  • Q represents a monovalent organic group having 1 to 20 carbon atoms.
  • pK BH in acetonitrile in an organic base containing a nitrogen atom is 20 or more, the production method according to any one of [1] to [3].
  • the organic base containing a nitrogen atom is an organic base having a phosphazene structure, an organic base having a guanidine structure, an organic base having an amidine structure, or an organic base having a proazaphosphatran structure.
  • a numerical range expressed using “to” means a range including numerical values described before and after “to” as a lower limit value and an upper limit value.
  • a compound represented by the formula (4) described below (hereinafter also referred to as “compound 4”) and a compound represented by the formula (5) described below (hereinafter also referred to as “compound 5”) are nitrogen.
  • a compound represented by the following formula (1) (hereinafter also referred to as “compound 1”) and a compound represented by the following formula (2) (hereinafter also referred to as “compound 2”).
  • a compound represented by the following formula (3) hereinafter also referred to as “compound 3”.
  • R represents an alkyl group or aryl group having 1 to 10 carbon atoms, an alkyl group or aryl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom.
  • a compound represented by the formula (1-1) is preferable.
  • Formula (1-1) CH 3 C (O) R ′ R ′ represents an alkyl group having 1 to 10 carbon atoms, an alkyl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom.
  • R is preferably a methyl group, an ethyl group, a trifluoromethyl group, or a hydrogen atom.
  • Examples of compound 1 include acetone, methyl ethyl ketone, 1,1,1-trifluoroacetone, acetaldehyde, and acetophenone.
  • X is a halogen atom.
  • Examples of the compound 2 include CHCl 3 , CHBr 3 , and CHI 3 , and CHCl 3 is preferable from the viewpoint of economy.
  • Q represents a monovalent organic group having 1 to 20 carbon atoms.
  • the monovalent organic group include a monovalent hydrocarbon group or a monovalent hydrocarbon group having a hetero atom.
  • the monovalent hydrocarbon group in the above formula (3) may be linear, branched or cyclic, and may be saturated or unsaturated.
  • Examples of the linear monovalent hydrocarbon group include a methyl group, an ethyl group, an n-propyl group, and a vinyl group.
  • Examples of the branched monovalent hydrocarbon group include isopropyl group, isobutyl group, t-butyl group and the like.
  • the cyclic monovalent hydrocarbon group include an alicyclic hydrocarbon group and an aromatic hydrocarbon group.
  • Examples of the alicyclic hydrocarbon group include a monocyclic saturated hydrocarbon group such as a cyclohexyl group, a polycyclic alicyclic hydrocarbon group such as a decacyclonaphthyl group, a bridged cyclic saturated carbon such as a norbornyl group and an adamantyl group. Spiro hydrocarbon groups such as a hydrogen group and spiro [3.4] octyl group can be mentioned.
  • Examples of the aromatic hydrocarbon group include a phenyl group, a benzyl group, a naphthyl group, and a biphenyl group.
  • the “monovalent hydrocarbon group having a hetero atom” in the above formula (3) means that —O—, —S— or —NH— is inserted between the carbon atom-carbon atom bond of the monovalent hydrocarbon group. Or a group in which the hydrogen atom in the monovalent hydrocarbon group is substituted with a substituent such as a group having a halogen atom or an oxygen atom (for example, a hydroxyl group or a carbonyl group).
  • the cyclic monovalent hydrocarbon group may be either aromatic or non-aromatic.
  • the aromatic heterocyclic group examples include pyridyl group, thiophenyl group, quinolyl group, isoquinolyl group, thiazolyl group, and benzothiazolyl group.
  • the non-aromatic heterocyclic group examples include an epoxyethyl group, a glycidyl group, an epoxycyclohexyl group, a tetrahydrofuranyl group, and a dihydrofuranyl group.
  • the linear or branched monovalent hydrocarbon is a group in which the hydrogen atom in the linear or branched monovalent hydrocarbon group is substituted with a fluorine atom.
  • a group in which two hydrogen atoms in the linear or branched monovalent hydrocarbon group are substituted with oxygen atoms to form a carbonyl group.
  • Q in the above formula (3) include linear alkyl groups having 1 to 10 carbon atoms (methyl group, ethyl group, propyl group, butyl group, etc.), cyclic groups having 6 to 10 carbon atoms.
  • Alkyl groups cyclohexyl group, norbornyl group, adamantyl group, etc.
  • alkyl groups containing an etheric oxygen atom having 2-10 carbon atoms polyoxyalkylalkyl group, glycidyl group, dihydrofuranyl group, etc.
  • 10 aromatic hydrocarbon groups phenyl group, aralkyl group (benzyl group), etc.
  • C2-C10 fluoroalkyl groups R F CH 2 —, R F CH 2 CH 2 —, etc., where R F is the number of carbon atoms.
  • Specific examples of the fluoroalkyl group having 2 to 10 carbon atoms include CF 3 CH 2 —, (CF 3 ) 2 CH—, CF 3 CF 2 CF 2 CF 2 CH 2 CH 2 —, and CF 3 CF 2 CF 2 CF. 2 CF 2 CF 2 CH 2 CH 2 —.
  • fluoroalkyl group having 2 to 10 carbon atoms containing an etheric oxygen atom examples include CF 3 OCF 2 CF 2 OCF 2 CF 2 OCF 2 CH 2 —, CF 3 CF 2 OCF 2 CF 2 OCF 2 CF 2 OCF 2 CH 2 —.
  • the present invention is carried out in the presence of an organic base containing a nitrogen atom.
  • the “organic base” in the present invention is a general term for organic compounds used as a base.
  • Organic bases containing nitrogen atoms include primary amines, secondary amines, tertiary amines, organic bases having a phosphazene structure, organic bases having a guanidine structure, organic bases having an amidine structure, and proazaphospha Examples include organic bases having a tolan structure.
  • the primary amine, secondary amine, and tertiary amine include an organic base having a phosphazene structure, an organic base having a guanidine structure, an organic base having an amidine structure, and proazaphosphatran.
  • Organic bases having a structure are not included.
  • Examples of the primary amine include ethylamine, propylamine, octylamine, cyclohexylamine, 1,5-diaminopentane, N-methylbenzylamine, 4,4′-methylenedianiline and the like.
  • Examples of the secondary amine include dimethylamine and diethylamine.
  • the “phosphazene structure” in the present invention means a structure represented by the following formula (B1) (“*” in the formula represents a bonding position with another group or atom).
  • the “guanidine structure” in the present invention means a structure represented by the following formula (B2) (“*” in the formula represents a bonding position with another group or atom).
  • the “amidine structure” in the present invention means a structure represented by the following formula (B3) (“*” in the formula represents a bonding position with another group or atom).
  • the “organic base having a proazaphosphatran structure” in the present invention is a structure represented by the following formula (B4) (“*” in the formula represents a bonding position with another group or atom). means.
  • the organic base containing a nitrogen atom is preferably an organic base having no nitrogen atom bonded to a hydrogen atom from the viewpoint of further improving the yield of compound 4 or compound 5.
  • the organic base containing a nitrogen atom is an organic base having a phosphazene structure, an organic base having a guanidine structure, or an organic substance having an amidine structure because the yield of the compound 4 is further improved among the organic bases containing a nitrogen atom.
  • a base or an organic base having a proazaphosphatran structure is preferable, and it is more preferable that these organic bases do not have a nitrogen atom bonded to a hydrogen atom.
  • PK BH in acetonitrile organic bases including the nitrogen atom is preferably 20 or more, more preferably 22 or more, more preferably 24 or more. If pK BH of organic bases containing nitrogen atom is 20 or more, the yield of compound 4 or compound 5 is further improved. Incidentally, pK BH is usually 45 or less.
  • pK BH is an index representing the degree of basicity, and the basicity is higher as pK BH is larger.
  • the pK BH of the organic base B in the solvent S is expressed as follows using the acid dissociation constant K BH of the conjugate acid HB + of the base B defined by the following formula (X) and the following formula (Y): Calculated by the formula (Z).
  • pK BH of organic bases including the nitrogen atom is a value in acetonitrile.
  • “ ⁇ ” in the following formula (Y) represents an activity coefficient.
  • the pK BH of an organic base in acetonitrile containing the nitrogen atom Table 1 of "J.Org.Chem.2005,70,1019-1028". The value shown in pKa (AN) b may be adopted.
  • the organic base containing a nitrogen atom may be used alone or in combination of two or more.
  • the organic base containing a nitrogen atom may be present in the system all at once, or may be partially introduced into the system by split charging or the like.
  • compound 4 which is an ⁇ , ⁇ -unsaturated acid ester or compound 5 which is an ⁇ -haloester is obtained as a target product.
  • both compound 4 and compound 5 may be obtained, or only one of compound 4 or compound 5 may be obtained.
  • Compound 4 is used as a raw material for a monomer such as a chemical product or a coating agent. If dehydrochlorination of compound 5 is carried out, it can be used as compound 4.
  • Formula (4) CH 2 CRC (O) OQ
  • Formula (5) CH 3 CXRC (O) OQ
  • R, X and Q are as defined above.
  • the reaction of Compound 1, Compound 2, and Compound 3 is preferably performed in the presence of an aprotic polar solvent in addition to the organic base containing the nitrogen atom.
  • an aprotic polar solvent examples include dimethylformamide, dimethylacetamide, ⁇ -butyrolactone, ⁇ -valerolactone, ⁇ -caprolactone, dimethyl sulfoxide, tetramethylene sulfoxide, 1-methyl-2-pyrrolidone, tetrahydrofuran, dimethylurea, 1, 1,3,3-tetramethylurea, acetonitrile, diglyme and the like can be mentioned.
  • the amount of compound 1 used is preferably 1 to 10-fold mol, more preferably 1 to 7-fold mol, and even more preferably 1 to 5-fold mol based on the amount of compound 2. If the usage-amount of the compound 1 is in the said range, the production amount of the by-product produced at the time of reaction will decrease.
  • the amount of compound 3 used is preferably 1 to 10 times the mole, more preferably 1 to 5 times the mole, and still more preferably 1 to 3 times the mole of compound 2. If the usage-amount of the compound 3 is the said upper limit, the production amount of a by-product will decrease.
  • the amount of the organic base containing a nitrogen atom is preferably 2 times mol or more, more preferably 3 times mol or more with respect to the amount of compound 2 used.
  • the amount of the organic base containing a nitrogen atom is usually 5 times or less the amount of compound 2 used. If the amount of the organic base containing a nitrogen atom is 2 times or more, it is a stoichiometrically appropriate amount when the target product in the production method of the present invention is the compound (4).
  • the amount of the aprotic polar solvent used is preferably 0.01 to 100 L, more preferably 0.1 to 1 L, relative to 1 mol of Compound 2.
  • compound 4 is obtained in one pot.
  • Base represents an organic base having a nitrogen atom
  • MMA represents methyl methacrylate which is one embodiment of Compound 4.
  • the compound obtained immediately before MMA is methyl 2-chloro-2-methylpropanoate which is one embodiment of compound 5.
  • the manufacturing cost can be reduced because the process can be simplified as compared with the conventional production method in which the raw material compound is reacted stepwise.
  • dehydrochlorination of compound 5 obtained by the production method of the present invention When dehydrochlorination of compound 5 obtained by the production method of the present invention is carried out, compound 4 is obtained.
  • the dehydrochlorination of Compound 5 can be easily carried out by the methods described in, for example, US Pat. No. 2013648, US Pat. No. 2,199,774, and International Publication No. 2014/038489. Specifically, it is preferably carried out based on Step B described in paragraphs 0043 to 0053 of International Publication No. 2014/038489, a method of reacting Compound 5 with a basic compound, The method of irradiating with an ultrasonic wave, a microwave, etc. is mentioned.
  • metal hydroxides, metal oxides, metal carbonates, metal alkoxides, metal amides, and amines are preferable because they are easily available.
  • Metal hydroxides, metal oxides, metal carbonates, metals Alkoxides and amines are more preferred. Examples of the metal in these compounds include lithium, sodium, potassium, calcium, and magnesium.
  • One of the by-products in the production method of the compound 4 of the present invention is a by-product based on an organic base having a nitrogen atom.
  • a by-product based on an organic base having a nitrogen atom is specifically a hydrohalide salt (for example, hydrochloride) of an organic base having a nitrogen atom.
  • a by-product based on an organic base having a nitrogen atom can be regenerated as an organic base having a nitrogen atom by dehydrohalogenation (for example, dehydrochlorination) as shown in the following reaction mechanism.
  • the recovered hydrogen halide (for example, hydrogen chloride) can be reused as a raw material for the compound 2 of the present invention, as exemplified in the following reaction mechanism.
  • “Base” in the following reaction mechanism means an organic base having a nitrogen atom.
  • the organic base having a nitrogen atom may be used while being supported on a carrier. That is, after carrying out the production method of the compound 4 using a carrier on which an organic base having a nitrogen atom is supported, this is recovered and dehydrohalogenated (for example, dehydrochlorinated) as described above, An organic base having a nitrogen atom supported on a carrier can be regenerated and reused.
  • the carrier include fine particles such as carbon black, silica (for example, colloidal silica, fumed silica, wet silica, silicate mineral), metal oxide, and metal nitride.
  • Japanese Patent Application Laid-Open No. 08-157570 can be referred to as a method for supporting an organic base having a nitrogen atom on a carrier.
  • Examples 27 to 29 are comparative examples.
  • surface mentioned later shows a mass reference
  • MMA methacrylate
  • 2-chloro Formation of methyl -2-methylpropanoate was confirmed.
  • the reaction yields of MMA and methyl 2-chloro-2-methylpropanoate were 61 mol% and 7.8 mol% based on chloroform, respectively.
  • Example 2 to Example 29 As shown in Table 1, Table 2 and Table 3, Examples 2 to 29 were carried out in the same manner as in Example 1 except that at least one of the type of base, the type of raw materials used, the reaction solvent and the reaction conditions was changed. Carried out. The reaction yield of the product in each example is summarized in Table 1.
  • compound 4 and compound 5 are methyl methacrylate and methyl 2-chloro-2-methylpropanoate in order when the used raw material combination is S1 to S13, and when the used raw material combination is S14.
  • ethyl methacrylate and ethyl 2-chloro-2-methylpropanoate in this order, and when the raw material combination is S15, tert-butyl methacrylate and tert-butyl 2-chloro-2-methylpropanoate are in order.
  • CH 2 C (CH 3 ) C (O) OCH 2 CF 3 and CH 3 CCl (CH 3 ) C (O) OCH 2 CF 3 are used in this order.
  • Each value in the combination of raw materials used in Table 2 is the molar ratio of each raw material to 1 mol of chloroform. Moreover, "Solv.” In the used raw material combination (S11) in Table 2 means that 8 mol times or more of raw material was used with respect to 1 mol of chloroform. Reaction condition C5 in Table 3 means that the reaction was carried out at 50 ° C. for 18 hours and then at 80 ° C. for 24 hours.
  • Example 30 Acetone (75 mg, 13 mmol), t-Bu-P 1 (2.0 g, 8.4 mmol), methanol (0.13 g, 4.0 mmol), internal standard 1,4-dibromobenzene (37 mg, 0.15 mmol) Then, chloroform (0.30 g, 2.5 mmol) was slowly added to a solution containing acetonitrile (6.9 g) with stirring at 0 ° C., followed by stirring at 50 ° C. for 20 hours. Further, DBU (0.76 g, 5.0 mmol) was slowly added, and the mixture was stirred at reflux (80 ° C.) for 26 hours, and then the reaction solution obtained at 25 ° C.
  • Example 31 To a solution of methyl 2-chloro-2-methylpropanoate (2.58 g, 19 mmol), 1,4-dibromobenzene (0.117 g, 0.50 mmol) as an internal standard in acetonitrile (8.0 mL) while stirring, 1 , 8-diazabicyclo [5.4.0] undec-7-ene (DBU, 3.21 g, 21 mmol) was added slowly. The reaction mixture was reacted under reflux for 13 hours. The formation of methyl methacrylate (MMA) was confirmed by 1 H-NMR analysis, and the reaction yield was 97 mol% based on methyl 2-chloro-2-methylpropanoate.
  • DBU 8-diazabicyclo [5.4.0] undec-7-ene
  • Examples 32 to 33 As shown in Tables 4 and 5, Examples 32 to 33 were carried out in the same manner as Example 1 except that at least one of the type of base, the type of raw material used, the reaction solvent and the reaction conditions was changed.
  • the reaction yield of the product in each example is summarized in Table 4.
  • Table 4 the reaction yields of compound 4 and compound 5 which are reaction products are based on chloroform (bromoform in Example 32), and the total value is the total reaction yield of compound 4 and compound 5.
  • Each value in the used raw material combinations in Table 5 is the molar ratio of each raw material to 1 mol of chloroform (1 mol of bromoform in Example 32).
  • Reaction condition C5 in Table 4 means that the reaction was carried out at 50 ° C. for 18 hours and then at 80 ° C. for 24 hours.

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Abstract

The present invention provides a production method for an α,β-unsaturated acid ester or an α-haloester, the method being capable of producing the α,β-unsaturated acid ester or α-haloester through a few steps. The method of the present invention, which is for producing a compound represented by the formula CH2=CRC(O)OQ, comprises reacting a compound represented by CH3C(O)R, CHX3, and a compound represented by the formula QOH in the presence of an organic base containing a nitrogen atom. In the formulae, R represents a C1-10 alkyl or aryl group, a C1-10 hetero-atom-containing alkyl or aryl group, or a hydrogen atom, X represents a halogen atom, and Q represents a C1-20 monovalent organic group.

Description

α，β－不飽和酸エステルまたはα－ハロエステルの製造方法Process for producing α, β-unsaturated ester or α-haloester
　本発明は、α，β－不飽和酸エステルまたはα－ハロエステルの製造方法に関する。 The present invention relates to a method for producing an α, β-unsaturated acid ester or an α-haloester.
　アクリル酸エステルおよびメタクリル酸エステル等のα，β－不飽和酸エステルの製造方法として、種々の方法が知られている。
　非特許文献１では、アセトンとクロロホルムから１，１，１－トリクロロ－２－メチル－２－プロパノール（ＴＣＭＰ）を得て、つぎにＴＣＭＰから２－メトキシ－２－メチルプロパン酸を得た後、そのメチルエステルを得て、さらにその脱アルコールによってメタクリル酸メチル（ＭＭＡ）を得る方法が開示されている。非特許文献１に記載のＭＭＡの製造方法は、下記ステップＡ～Ｄの通りである。
　　ステップＡ：ＣＨ３Ｃ（Ｏ）ＣＨ３　＋　ＣＨＣｌ３　→　Ｃ（ＣＨ３）２（ＯＨ）（ＣＣｌ３）
　　ステップＢ：Ｃ（ＣＨ３）２（ＯＨ）（ＣＣｌ３）　＋　４ＫＯＨ　＋　ＣＨ３ＯＨ　→　Ｃ（ＣＨ３）２（ＯＣＨ３）（ＣＯＯＫ）＋　３ＫＣｌ　＋　３Ｈ２Ｏ
　　ステップＣ：Ｃ（ＣＨ３）２（ＯＣＨ３）（ＣＯＯＫ）　＋　ＣＨ３ＯＨ　→　Ｃ（ＣＨ３）２（ＯＣＨ３）（ＣＯＯＣＨ３）　＋　ＫＯＨ
　　ステップＤ：Ｃ（ＣＨ３）２（ＯＣＨ３）（ＣＯＯＣＨ３）→　ＣＨ２＝Ｃ（ＣＨ３）Ｃ（Ｏ）ＯＣＨ３　＋　ＣＨ３ＯＨ Various methods are known for producing α, β-unsaturated acid esters such as acrylic acid esters and methacrylic acid esters.
In Non-Patent Document 1, 1,1,1-trichloro-2-methyl-2-propanol (TCMP) is obtained from acetone and chloroform, and then 2-methoxy-2-methylpropanoic acid is obtained from TCMP. A method for obtaining the methyl ester and further obtaining the methyl methacrylate (MMA) by dealcoholization is disclosed. The manufacturing method of MMA described in Non-Patent Document 1 is as steps A to D below.
Step A: CH 3 C (O) CH 3 + CHCl 3 → C (CH 3 ) 2 (OH) (CCl 3 )
Step B: C (CH 3) 2 (OH) (CCl 3) + 4KOH + CH 3 OH → C (CH 3) 2 (OCH 3) (COOK) + 3KCl + 3H 2 O
Step C: C (CH 3) 2 (OCH 3) (COOK) + CH 3 OH → C (CH 3) 2 (OCH 3) (COOCH 3) + KOH
Step D: C (CH 3 ) 2 (OCH 3 ) (COOCH 3 ) → CH 2 ═C (CH 3 ) C (O) OCH 3 + CH 3 OH
　特許文献１には、塩化亜鉛の存在下で、ＴＣＭＰ等を反応させて反応粗液を得た後、反応粗液とメタノールを反応させて、ＭＭＡを得る方法が開示されている（実施例３）。特許文献２では、酸化亜鉛の存在下で、ＴＣＭＰとメタノールとを反応させて、ＭＭＡを得る方法が開示されている（実施例１）。 Patent Document 1 discloses a method of obtaining MMA by reacting TCMP and the like in the presence of zinc chloride to obtain a reaction crude liquid and then reacting the reaction crude liquid with methanol (Example 3). ). Patent Document 2 discloses a method of obtaining MMA by reacting TCMP with methanol in the presence of zinc oxide (Example 1).
国際公開第２０１４／０３８４８９号International Publication No. 2014/038489 国際公開第２０１５／００５２４３号International Publication No. 2015/005243
　上記非特許文献１に記載のＭＭＡの製造方法は、多段階反応で実施されるため、工程の複雑さや製造コスト等の観点から、経済的ではない。
　また、特許文献１～２に記載のＭＭＡの製造方法は、予め製造されたＴＣＭＰを用いている。そのため、ＴＣＭＰの製造をＭＭＡの製造に含めた場合、ＭＭＡは実質的に多段階反応で製造されているといえるため、経済的な観点から改良の余地がある。
　このように、従来α，β－不飽和酸エステルは、多段階工程を要する反応で製造され、短工程、好ましくは１ポットで製造するのが困難であった。 Since the MMA production method described in Non-Patent Document 1 is performed in a multistage reaction, it is not economical from the viewpoints of process complexity and production cost.
In addition, the MMA manufacturing methods described in Patent Documents 1 and 2 use TCMP manufactured in advance. Therefore, when TCMP production is included in MMA production, it can be said that MMA is substantially produced by a multi-step reaction, and therefore there is room for improvement from an economical viewpoint.
As described above, α, β-unsaturated acid esters are conventionally produced by a reaction that requires a multi-step process, and it has been difficult to produce a short process, preferably in one pot.
　本発明は、上記課題に鑑みてなされ、α，β－不飽和酸エステルまたはα－ハロエステルを短工程（好ましくは１ポット）で得るための製造方法の提供を目的とする。 The present invention has been made in view of the above problems, and an object of the present invention is to provide a production method for obtaining an α, β-unsaturated acid ester or α-haloester in a short process (preferably 1 pot).
　本発明者は、上記課題について鋭意検討した結果、窒素原子を含む有機塩基の存在下、後述する式（１）、式（２）および式（３）で表される化合物を反応させれば、後述する式（４）で表される化合物（α，β－不飽和酸エステル）または後述する式（５）で表される化合物（α－ハロエステル）が短工程（好ましくは１ポット）で得られることを見出し、本発明に至った。
　すなわち、本発明者は、以下の構成により上記課題が解決できることを見出した。
［１］　窒素原子を含む有機塩基の存在下、下式（１）で表される化合物と、下式（２）で表される化合物と、下式（３）で表される化合物とを反応させて下式（４）で表される化合物または下式（５）で表される化合物を得る、下式（４）で表される化合物または下式（５）で表される化合物の製造方法。
　式（１）　ＣＨ３Ｃ（Ｏ）Ｒ
　式（２）　ＣＨＸ３
　式（３）　ＱＯＨ
　式（４）　ＣＨ２＝ＣＲＣ（Ｏ）ＯＱ
　式（５）　ＣＨ３ＣＸＲＣ（Ｏ）ＯＱ
　式中の記号は、以下の意味を表す。
　Ｒは、炭素数１～１０のアルキル基もしくはアリール基、炭素数１～１０のヘテロ原子を含むアルキル基もしくはアリール基、または水素原子を表す。
　Ｘはハロゲン原子を表す。
　Ｑは、炭素数１～２０の１価有機基を表す。 As a result of earnestly examining the above problems, the present inventor reacted the compounds represented by formula (1), formula (2) and formula (3) described below in the presence of an organic base containing a nitrogen atom. A compound represented by formula (4) described later (α, β-unsaturated ester) or a compound represented by formula (5) described later (α-haloester) is obtained in a short process (preferably 1 pot). The present invention has been found.
That is, the present inventor has found that the above problem can be solved by the following configuration.
[1] A compound represented by the following formula (1), a compound represented by the following formula (2), and a compound represented by the following formula (3) are reacted in the presence of an organic base containing a nitrogen atom. A method for producing a compound represented by the following formula (4) or a compound represented by the following formula (5), wherein a compound represented by the following formula (4) or a compound represented by the following formula (5) is obtained: .
Formula (1) CH 3 C (O) R
Formula (2) CHX 3
Formula (3) QOH
Formula (4) CH 2 = CRC (O) OQ
Formula (5) CH 3 CXRC (O) OQ
The symbols in the formula represent the following meanings.
R represents an alkyl group or aryl group having 1 to 10 carbon atoms, an alkyl group or aryl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom.
X represents a halogen atom.
Q represents a monovalent organic group having 1 to 20 carbon atoms.
［２］　窒素原子を含む有機塩基の存在下、下式（１－１）で表される化合物と下式（２－１）で表される化合物と下式（３）で表される化合物とを反応させて下式（４－１）で表される化合物または下式（５－１）で表される化合物を得る、［１］に記載の製造方法。
　式（１－１）　ＣＨ３Ｃ（Ｏ）Ｒ´
　式（２－１）　ＣＨＣｌ３
　式（３）　ＱＯＨ
　式（４－１）　ＣＨ２＝ＣＲ´Ｃ（Ｏ）ＯＱ
　式（５－１）　ＣＨ３ＣＣｌＲ´Ｃ（Ｏ）ＯＱ
　式中の記号は、以下の意味を表す。
　Ｒ´は、炭素数１～１０のアルキル基、炭素数１～１０のヘテロ原子を含むアルキル基、または水素原子を表す。
　Ｑは、炭素数１～２０の１価有機基を表す。
［３］　前記窒素原子を含む有機塩基が、水素原子と結合した窒素原子を有しない、［１］または［２］に記載の製造方法。
［４］　前記窒素原子を含む有機塩基のアセトニトリル中でのｐＫＢＨが、２０以上である、［１］～［３］のいずれか１つに記載の製造方法。
［５］　前記窒素原子を含む有機塩基が、ホスファゼン構造を有する有機塩基、グアニジン構造を有する有機塩基、アミジン構造を有する有機塩基、またはプロアザホスファトラン構造を有する有機塩基である、［１］～［４］のいずれか１つに記載の製造方法。
［６］　ＲまたはＲ´が、メチル基、エチル基、トリフルオロメチル基、または水素原子である、［１］～［５］のいずれか１つに記載の製造方法。
［７］　Ｑが、炭素数１～２０の１価炭化水素基またはヘテロ原子を有する炭素数１～２０の１価炭化水素基である、［１］～［６］のいずれか１つに記載の製造方法。
［８］　前記式（２）で表される化合物の使用量に対して、前記式（１）で表される化合物の使用量が１～１０倍モルである、［１］～［７］のいずれか１つに記載の製造方法。
［９］　前記式（２）で表される化合物の使用量に対して、前記式（３）で表される化合物の使用量が１～１０倍モルである、［１］～［８］のいずれか１つに記載の製造方法。
［１０］　前記式（２）で表される化合物の使用量に対して、前記窒素原子を含む有機塩基の使用量が２倍モル以上である、［１］～［９］のいずれか１つに記載の製造方法。
［１１］　前記反応が、非プロトン性極性溶剤の存在下で行われる、［１］～［１０］のいずれか１つに記載の製造方法。
［１２］　前記式（４）で表される化合物を得る、［１］～［１１］のいずれか１つに記載の製造方法。
［１３］　［１］～［１１］のいずれか１つに記載の製造方法で（５）で表される化合物を得て、該化合物を脱塩化水素させて、式（４）で表される化合物を得る、式（４）で表される化合物の製造方法。 [2] In the presence of an organic base containing a nitrogen atom, a compound represented by the following formula (1-1), a compound represented by the following formula (2-1), and a compound represented by the following formula (3): To obtain the compound represented by the following formula (4-1) or the compound represented by the following formula (5-1).
Formula (1-1) CH 3 C (O) R ′
Formula (2-1) CHCl 3
Formula (3) QOH
Formula (4-1) CH 2 = CR′C (O) OQ
Formula (5-1) CH 3 CClR′C (O) OQ
The symbols in the formula represent the following meanings.
R ′ represents an alkyl group having 1 to 10 carbon atoms, an alkyl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom.
Q represents a monovalent organic group having 1 to 20 carbon atoms.
[3] The production method according to [1] or [2], wherein the organic base containing a nitrogen atom does not have a nitrogen atom bonded to a hydrogen atom.
[4] pK BH in acetonitrile in an organic base containing a nitrogen atom is 20 or more, the production method according to any one of [1] to [3].
[5] The organic base containing a nitrogen atom is an organic base having a phosphazene structure, an organic base having a guanidine structure, an organic base having an amidine structure, or an organic base having a proazaphosphatran structure. [1] The production method according to any one of [4] to [4].
[6] The production method according to any one of [1] to [5], wherein R or R ′ is a methyl group, an ethyl group, a trifluoromethyl group, or a hydrogen atom.
[7] Any one of [1] to [6], wherein Q is a monovalent hydrocarbon group having 1 to 20 carbon atoms or a monovalent hydrocarbon group having 1 to 20 carbon atoms having a hetero atom. Manufacturing method.
[8] The amount of the compound represented by the formula (1) is 1 to 10 times mol of the amount of the compound represented by the formula (2). The manufacturing method as described in any one.
[9] The amount of the compound represented by the formula (3) is 1 to 10 times mol of the amount of the compound represented by the formula (2). The manufacturing method as described in any one.
[10] Any one of [1] to [9], wherein the amount of the organic base containing a nitrogen atom is 2 times or more the amount of the compound represented by the formula (2) The manufacturing method as described in.
[11] The production method according to any one of [1] to [10], wherein the reaction is performed in the presence of an aprotic polar solvent.
[12] The production method according to any one of [1] to [11], wherein the compound represented by the formula (4) is obtained.
[13] The compound represented by (5) is obtained by the production method according to any one of [1] to [11], the compound is dehydrochlorinated, and represented by the formula (4) The manufacturing method of the compound represented by Formula (4) which obtains a compound.
　以下に示すように、本発明によれば、α，β－不飽和酸エステルまたはα－ハロエステルが短工程で容易に得られる製造方法を提供できる。 As described below, according to the present invention, it is possible to provide a production method in which α, β-unsaturated acid ester or α-haloester can be easily obtained in a short process.
　本明細書において、「～」を用いて表される数値範囲は、「～」の前後に記載される数値を下限値および上限値として含む範囲を意味する。 In this specification, a numerical range expressed using “to” means a range including numerical values described before and after “to” as a lower limit value and an upper limit value.
　本発明において、後述する式（４）で表される化合物（以下「化合物４」ともいう。）および後述する式（５）で表される化合物（以下「化合物５」ともいう。）は、窒素原子を含む有機塩基の存在下、下式（１）で表される化合物（以下「化合物１」ともいう。）と下式（２）で表される化合物（以下「化合物２」ともいう。）と、下式（３）で表される化合物（以下「化合物３」ともいう。）とを反応させて得られる。 In the present invention, a compound represented by the formula (4) described below (hereinafter also referred to as “compound 4”) and a compound represented by the formula (5) described below (hereinafter also referred to as “compound 5”) are nitrogen. In the presence of an organic base containing an atom, a compound represented by the following formula (1) (hereinafter also referred to as “compound 1”) and a compound represented by the following formula (2) (hereinafter also referred to as “compound 2”). And a compound represented by the following formula (3) (hereinafter also referred to as “compound 3”).
　本発明において、化合物１、化合物２、および化合物３が原料として使用される。
　　式（１）　ＣＨ３Ｃ（Ｏ）Ｒ
　　式（２）　ＣＨＸ３
　　式（３）　ＱＯＨ In the present invention, Compound 1, Compound 2, and Compound 3 are used as raw materials.
Formula (1) CH 3 C (O) R
Formula (2) CHX 3
Formula (3) QOH
　上記式（１）中、Ｒは、炭素数１～１０のアルキル基もしくはアリール基、炭素数１～１０のヘテロ原子を含むアルキル基もしくはアリール基、または水素原子を表す。化合物１としては、式（１－１）で表される化合物が好ましい。
　　式（１－１）　ＣＨ３Ｃ（Ｏ）Ｒ´
　Ｒ´は、炭素数１～１０のアルキル基、炭素数１～１０のヘテロ原子を含むアルキル基または水素原子を表す。
　Ｒは、化合物４の合成適性の観点から、メチル基、エチル基、トリフルオロメチル基または水素原子が好ましい。
　化合物１としては、例えばアセトン、メチルエチルケトン、１，１，１－トリフルオロアセトン、アセトアルデヒド、アセトフェノンが挙げられる。
　上記式（２）中、Ｘはハロゲン原子である。
　化合物２としては、例えばＣＨＣｌ３、ＣＨＢｒ３、ＣＨＩ３が挙げられるが、経済性の観点からＣＨＣｌ３が好ましい。 In the above formula (1), R represents an alkyl group or aryl group having 1 to 10 carbon atoms, an alkyl group or aryl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom. As the compound 1, a compound represented by the formula (1-1) is preferable.
Formula (1-1) CH 3 C (O) R ′
R ′ represents an alkyl group having 1 to 10 carbon atoms, an alkyl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom.
From the viewpoint of suitability for synthesis of compound 4, R is preferably a methyl group, an ethyl group, a trifluoromethyl group, or a hydrogen atom.
Examples of compound 1 include acetone, methyl ethyl ketone, 1,1,1-trifluoroacetone, acetaldehyde, and acetophenone.
In the above formula (2), X is a halogen atom.
Examples of the compound 2 include CHCl 3 , CHBr 3 , and CHI 3 , and CHCl 3 is preferable from the viewpoint of economy.
　上記式（３）中、Ｑは、炭素数１～２０の１価有機基を表す。１価有機基としては、例えば１価炭化水素基またはヘテロ原子を有する１価炭化水素基が挙げられる。
　上記式（３）における１価炭化水素基は、直鎖状、分岐状または環状であってもよく、飽和または不飽和であってもよい。
　直鎖状の１価炭化水素基としては、例えばメチル基、エチル基、ｎ－プロピル基、ビニル基等が挙げられる。
　分岐状の１価炭化水素基としては、例えばイソプロピル基、イソブチル基、ｔ－ブチル基等が挙げられる。
　環状の１価炭化水素基としては、例えば脂環式炭化水素基、芳香族炭化水素基等が挙げられる。脂環式炭化水素基としては、例えばシクロヘキシル基等の単環式飽和炭化水素基、デカシクロナフチル基等の多環式脂環式炭化水素基、ノルボルニル基、アダマンチル基等の架橋環式飽和炭化水素基、スピロ［３．４］オクチル基等のスピロ炭化水素基が挙げられる。芳香族炭化水素基としては、例えばフェニル基、ベンジル基、ナフチル基、ビフェニル基等が挙げられる。 In the above formula (3), Q represents a monovalent organic group having 1 to 20 carbon atoms. Examples of the monovalent organic group include a monovalent hydrocarbon group or a monovalent hydrocarbon group having a hetero atom.
The monovalent hydrocarbon group in the above formula (3) may be linear, branched or cyclic, and may be saturated or unsaturated.
Examples of the linear monovalent hydrocarbon group include a methyl group, an ethyl group, an n-propyl group, and a vinyl group.
Examples of the branched monovalent hydrocarbon group include isopropyl group, isobutyl group, t-butyl group and the like.
Examples of the cyclic monovalent hydrocarbon group include an alicyclic hydrocarbon group and an aromatic hydrocarbon group. Examples of the alicyclic hydrocarbon group include a monocyclic saturated hydrocarbon group such as a cyclohexyl group, a polycyclic alicyclic hydrocarbon group such as a decacyclonaphthyl group, a bridged cyclic saturated carbon such as a norbornyl group and an adamantyl group. Spiro hydrocarbon groups such as a hydrogen group and spiro [3.4] octyl group can be mentioned. Examples of the aromatic hydrocarbon group include a phenyl group, a benzyl group, a naphthyl group, and a biphenyl group.
　上記式（３）における「ヘテロ原子を有する１価炭化水素基」とは、上記１価炭化水素基の炭素原子－炭素原子結合間に、－Ｏ－、－Ｓ－または－ＮＨ－が挿入された基であるか、または、上記１価炭化水素基における水素原子がハロゲン原子、酸素原子を有する基（例えば水酸基、カルボニル基）等の置換基に置換された基である。
　ヘテロ原子を有する１価炭化水素基のうち、環状の１価炭化水素基としては、芳香族または非芳香族のいずれであってもよい。芳香族複素環基としては、例えばピリジル基、チオフェニル基、キノリル基、イソキノリル基、チアゾリル基、ベンゾチアゾリル基等が挙げられる。非芳香族複素環基としては、例えばエポキシエチル基、グリシジル基、エポキシシクロヘキシル基、テトラヒドロフラニル、ジヒドロフラニル基等が挙げられる。
　ヘテロ原子を有する１価炭化水素基のうち、直鎖状または分岐状の１価炭化水素としては、上記直鎖状または分岐状の１価炭化水素基における水素原子がフッ素原子に置換された基や、上記直鎖状または分岐状の１価炭化水素基における２個の水素原子が酸素原子で置換されてカルボニル基を形成した基が挙げられる。 The “monovalent hydrocarbon group having a hetero atom” in the above formula (3) means that —O—, —S— or —NH— is inserted between the carbon atom-carbon atom bond of the monovalent hydrocarbon group. Or a group in which the hydrogen atom in the monovalent hydrocarbon group is substituted with a substituent such as a group having a halogen atom or an oxygen atom (for example, a hydroxyl group or a carbonyl group).
Of the monovalent hydrocarbon groups having a hetero atom, the cyclic monovalent hydrocarbon group may be either aromatic or non-aromatic. Examples of the aromatic heterocyclic group include pyridyl group, thiophenyl group, quinolyl group, isoquinolyl group, thiazolyl group, and benzothiazolyl group. Examples of the non-aromatic heterocyclic group include an epoxyethyl group, a glycidyl group, an epoxycyclohexyl group, a tetrahydrofuranyl group, and a dihydrofuranyl group.
Among the monovalent hydrocarbon groups having a hetero atom, the linear or branched monovalent hydrocarbon is a group in which the hydrogen atom in the linear or branched monovalent hydrocarbon group is substituted with a fluorine atom. And a group in which two hydrogen atoms in the linear or branched monovalent hydrocarbon group are substituted with oxygen atoms to form a carbonyl group.
　上記式（３）中のＱの好適な具体例としては、炭素数１～１０の直鎖状のアルキル基（メチル基、エチル基、プロピル基、ブチル基等）、炭素数６～１０の環状のアルキル基（シクロヘキシル基、ノルボルニル基、アダマンチル基等）、炭素数２～１０のエーテル性酸素原子を含むアルキル基（ポリオキシアルキルアルキル基、グリシジル基、ジヒドロフラニル基等）、炭素数６～１０の芳香族炭化水素基（フェニル基、アラルキル基（ベンジル基）等）、炭素数２～１０のフルオロアルキル基（ＲＦＣＨ２－、ＲＦＣＨ２ＣＨ２－等。ＲＦは炭素数１～６のポリフルオロアルキル基を表す。）、および、エーテル性酸素原子を含む炭素数２～１０のフルオロアルキル基（ペルフルオロオキシアルキレン基を有するフルオロアルキル基等。）が挙げられる。
　炭素数２～１０のフルオロアルキル基の具体例としては、ＣＦ３ＣＨ２－、（ＣＦ３）２ＣＨ－、ＣＦ３ＣＦ２ＣＦ２ＣＦ２ＣＨ２ＣＨ２－、ＣＦ３ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＦ２ＣＨ２ＣＨ２－が挙げられる。
　エーテル性酸素原子を含む炭素数２～１０のフルオロアルキル基の具体例としては、ＣＦ３ＯＣＦ２ＣＦ２ＯＣＦ２ＣＦ２ＯＣＦ２ＣＨ２－、ＣＦ３ＣＦ２ＯＣＦ２ＣＦ２ＯＣＦ２ＣＦ２ＯＣＦ２ＣＨ２－が挙げられる。 Preferable specific examples of Q in the above formula (3) include linear alkyl groups having 1 to 10 carbon atoms (methyl group, ethyl group, propyl group, butyl group, etc.), cyclic groups having 6 to 10 carbon atoms. Alkyl groups (cyclohexyl group, norbornyl group, adamantyl group, etc.), alkyl groups containing an etheric oxygen atom having 2-10 carbon atoms (polyoxyalkylalkyl group, glycidyl group, dihydrofuranyl group, etc.), 10 aromatic hydrocarbon groups (phenyl group, aralkyl group (benzyl group), etc.), C2-C10 fluoroalkyl groups (R F CH 2 —, R F CH 2 CH 2 —, etc., where R F is the number of carbon atoms. Represents a 1 to 6 polyfluoroalkyl group), and a fluoroalkyl group having 2 to 10 carbon atoms containing an etheric oxygen atom (a fluoroalkyl having a perfluorooxyalkylene group) Etc..), And the like.
Specific examples of the fluoroalkyl group having 2 to 10 carbon atoms include CF 3 CH 2 —, (CF 3 ) 2 CH—, CF 3 CF 2 CF 2 CF 2 CH 2 CH 2 —, and CF 3 CF 2 CF 2 CF. 2 CF 2 CF 2 CH 2 CH 2 —.
Specific examples of the fluoroalkyl group having 2 to 10 carbon atoms containing an etheric oxygen atom include CF 3 OCF 2 CF 2 OCF 2 CF 2 OCF 2 CH 2 —, CF 3 CF 2 OCF 2 CF 2 OCF 2 CF 2 OCF 2 CH 2 —.
　本発明は、窒素原子を含む有機塩基の存在下に行われる。本発明における「有機塩基」とは、塩基として用いられる有機化合物の総称である。
　窒素原子を含む有機塩基としては、第１級アミン、第２級アミン、第３級アミン、ホスファゼン構造を有する有機塩基、グアニジン構造を有する有機塩基、アミジン構造を有する有機塩基、およびプロアザホスファトラン構造を有する有機塩基等が挙げられる。
　なお、本発明において、第１級アミン、第２級アミンおよび第３級アミンには、ホスファゼン構造を有する有機塩基、グアニジン構造を有する有機塩基、アミジン構造を有する有機塩基、およびプロアザホスファトラン構造を有する有機塩基は含まれない。 The present invention is carried out in the presence of an organic base containing a nitrogen atom. The “organic base” in the present invention is a general term for organic compounds used as a base.
Organic bases containing nitrogen atoms include primary amines, secondary amines, tertiary amines, organic bases having a phosphazene structure, organic bases having a guanidine structure, organic bases having an amidine structure, and proazaphospha Examples include organic bases having a tolan structure.
In the present invention, the primary amine, secondary amine, and tertiary amine include an organic base having a phosphazene structure, an organic base having a guanidine structure, an organic base having an amidine structure, and proazaphosphatran. Organic bases having a structure are not included.
　第１級アミンとしては、例えばエチルアミン、プロピルアミン、オクチルアミン、シクロヘキシルアミン、１，５－ジアミノペンタン、Ｎ－メチルベンジルアミン、４，４’－メチレンジアニリン等が挙げられる。
　第２級アミンとしては、例えばジメチルアミン、ジエチルアミン等が挙げられる。
　第３級アミンとしては、例えばトリメチルアミン、トリエチルアミン（Ｅｔ３Ｎ）（ｐＫＢＨ＝１８．８２）、トリブチルアミン、１，８－ジアザビシクロ［２．２．２］オクタン（ＤＡＢＣＯ）（ｐＫＢＨ＝１８．２９）、４－イソプロピルモルホリン、４－ジメチルアミノピリジン等が挙げられる。 Examples of the primary amine include ethylamine, propylamine, octylamine, cyclohexylamine, 1,5-diaminopentane, N-methylbenzylamine, 4,4′-methylenedianiline and the like.
Examples of the secondary amine include dimethylamine and diethylamine.
As the tertiary amine, for example, trimethylamine, triethylamine (Et 3 N) (pK BH = 18.82), tributylamine, 1,8-diazabicyclo [2.2.2] octane (DABCO) (pK BH = 18. 29), 4-isopropylmorpholine, 4-dimethylaminopyridine and the like.
　本発明における「ホスファゼン構造」とは、下式（Ｂ１）で表される構造（式中の「＊」は他の基または原子との結合位置を表す。）を意味する。ホスファゼン構造を有する有機塩基としては、例えばｔｅｒｔ－ブチルイミノ－トリ(ピロリジノ)ホスホラン（ＢＴＰＰ）（ｐＫＢＨ＝２８．３５）、ｔｅｒｔ－ブチルイミノ－トリス（ジメチルアミノ）ホスホラン（ｔ－Ｂｕ－Ｐ１）（ｐＫＢＨ＝２６．９８）、２－ｔｅｒｔ－ブチルイミノ－２－ジエチルアミノ－１，３－ジメチルペルヒドロ－１，３，２－ジアザホスホリン（ＢＥＭＰ）等が挙げられる。
　本発明における「グアニジン構造」とは、下式（Ｂ２）で表される構造（式中の「＊」は他の基または原子との結合位置を表す。）を意味する。グアニジン構造を有する有機塩基としては、例えばグアニジン、１，１，３，３－テトラメチルグアニジン、１，３，４，６，７，８－ヘキサヒドロ－２Ｈ－ピリミド［１，２－ａ］ピリミジン（ＴＢＤ）（ｐＫＢＨ＝２６．０３）、１，３，４，６，７，８－ヘキサヒドロ－１－メチル－２Ｈ－ピリミド［１，２－ａ］ピリミジン（ＭＴＢＤ）（ｐＫＢＨ＝２５．４９）等が挙げられる。
　本発明における「アミジン構造」とは、下式（Ｂ３）で表される構造（式中の「＊」は他の基または原子との結合位置を表す。）を意味する。アミジン構造を有する有機塩基としては、例えばイミダゾール、１，８－ジアザビシクロ［５．４．０］ウンデカ－７－エン（ＤＢＵ）（ｐＫＢＨ＝２４．３４）、１，５－ジアザビシクロ［４．３．０］－５－ノネン（ＤＢＮ）（ｐＫＢＨ＝２３．８９）等が挙げられる。
　本発明における「プロアザホスファトラン構造を有する有機塩基」とは、下式（Ｂ４）で表される構造（式中の「＊」は他の基または原子との結合位置を表す。）を意味する。プロアザホスファトラン構造を有する有機塩基としては、例えば２，８，９－トリメチル－２，５，８，９－テトラアザ－１－ホスファビシクロ［３．３．３］ウンデカン（Ｖｅｒｋａｄｅ　ｂａｓｅ）（ｐＫＢＨ＝３２．９０）、２，８，９－トリイソプロピル－２，５，８，９－テトラアザ－１－ホスファビシクロ［３，３，３］ウンデカン、２，８，９－トリイソブチル－２，５，８，９－テトラアザ－１－ホスファビシクロ［３．３．３］ウンデカン等が挙げられる。 The “phosphazene structure” in the present invention means a structure represented by the following formula (B1) (“*” in the formula represents a bonding position with another group or atom). Examples of the organic base having a phosphazene structure include tert-butylimino-tri (pyrrolidino) phosphorane (BTPP) (pK BH = 28.35), tert-butylimino-tris (dimethylamino) phosphorane (t-Bu-P 1 ) ( pK BH = 26.98), 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) and the like.
The “guanidine structure” in the present invention means a structure represented by the following formula (B2) (“*” in the formula represents a bonding position with another group or atom). Examples of the organic base having a guanidine structure include guanidine, 1,1,3,3-tetramethylguanidine, 1,3,4,6,7,8-hexahydro-2H-pyrimido [1,2-a] pyrimidine ( TBD) (pK BH = 26.03), 1,3,4,6,7,8-hexahydro-1-methyl-2H-pyrimido [1,2-a] pyrimidine (MTBD) (pK BH = 25.49) ) And the like.
The “amidine structure” in the present invention means a structure represented by the following formula (B3) (“*” in the formula represents a bonding position with another group or atom). Examples of the organic base having an amidine structure include imidazole, 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) (pK BH = 24.34), 1,5-diazabicyclo [4.3. .0] -5-nonene (DBN) (pK BH = 23.89).
The “organic base having a proazaphosphatran structure” in the present invention is a structure represented by the following formula (B4) (“*” in the formula represents a bonding position with another group or atom). means. Examples of the organic base having a proazaphosphatran structure include 2,8,9-trimethyl-2,5,8,9-tetraaza-1-phosphabicyclo [3.3.3] undecane (Verkade base) ( pK BH = 32.90), 2,8,9-triisopropyl-2,5,8,9-tetraaza-1-phosphabicyclo [3,3,3] undecane, 2,8,9-triisobutyl- 2,5,8,9-tetraaza-1-phosphabicyclo [3.3.3] undecane and the like.
Figure JPOXMLDOC01-appb-C000001
Figure JPOXMLDOC01-appb-C000001
　上記窒素原子を含む有機塩基は、化合物４または化合物５の収率がより向上する点から、水素原子と結合した窒素原子を有しない有機塩基が好ましい。
　窒素原子を含む有機塩基は、上述した窒素原子を含む有機塩基の中でも、化合物４の収率がより向上する点から、ホスファゼン構造を有する有機塩基、グアニジン構造を有する有機塩基、アミジン構造を有する有機塩基、または、プロアザホスファトラン構造を有する有機塩基が好ましく、これらの有機塩基が水素原子と結合した窒素原子を有しないのがより好ましい。 The organic base containing a nitrogen atom is preferably an organic base having no nitrogen atom bonded to a hydrogen atom from the viewpoint of further improving the yield of compound 4 or compound 5.
The organic base containing a nitrogen atom is an organic base having a phosphazene structure, an organic base having a guanidine structure, or an organic substance having an amidine structure because the yield of the compound 4 is further improved among the organic bases containing a nitrogen atom. A base or an organic base having a proazaphosphatran structure is preferable, and it is more preferable that these organic bases do not have a nitrogen atom bonded to a hydrogen atom.
　上記窒素原子を含む有機塩基のアセトニトリル中でのｐＫＢＨは、２０以上が好ましく、２２以上がより好ましく、２４以上がさらに好ましい。窒素原子を含む有機塩基のｐＫＢＨが２０以上であれば、化合物４または化合物５の収率がより向上する。なお、ｐＫＢＨは、通常４５以下である。
　ここで、ｐＫＢＨは、塩基性の程度を表す指標であり、ｐＫＢＨが大きいほど、塩基性が高い。具体的には、溶媒Ｓ中の有機塩基ＢのｐＫＢＨは、下式（Ｘ）および下式（Ｙ）によって定義される塩基Ｂの共役酸ＨＢ＋の酸解離定数ＫＢＨを用いて、下式（Ｚ）により算出される。なお、本発明では、溶媒Ｓとしてアセトニトルを用い、上記窒素原子を含む有機塩基のｐＫＢＨはアセトニトリル中での値である。また、下式（Ｙ）の「α」は活量係数を表す。
　なお、本発明において、上記窒素原子を含む有機塩基のアセトニトリル中でのｐＫＢＨには、「Ｊ．Ｏｒｇ．Ｃｈｅｍ．２００５，７０，１０１９－１０２８」のＴａｂｌｅ １．のｐＫａ（ＡＮ）ｂに示された値等を採用してもよい。 PK BH in acetonitrile organic bases, including the nitrogen atom is preferably 20 or more, more preferably 22 or more, more preferably 24 or more. If pK BH of organic bases containing nitrogen atom is 20 or more, the yield of compound 4 or compound 5 is further improved. Incidentally, pK BH is usually 45 or less.
Here, pK BH is an index representing the degree of basicity, and the basicity is higher as pK BH is larger. Specifically, the pK BH of the organic base B in the solvent S is expressed as follows using the acid dissociation constant K BH of the conjugate acid HB + of the base B defined by the following formula (X) and the following formula (Y): Calculated by the formula (Z). In the present invention, using Acetonitrile as the solvent S, pK BH of organic bases, including the nitrogen atom is a value in acetonitrile. Further, “α” in the following formula (Y) represents an activity coefficient.
In the present invention, the pK BH of an organic base in acetonitrile containing the nitrogen atom, Table 1 of "J.Org.Chem.2005,70,1019-1028". The value shown in pKa (AN) b may be adopted.
Figure JPOXMLDOC01-appb-M000002
Figure JPOXMLDOC01-appb-M000002
　本発明の製造方法において、窒素原子を含む有機塩基は、１種のみを単独使用してもよく、２種以上を併用してもよい。また、本発明の製造方法において、窒素原子を含む有機塩基は、一括して系に存在させてもよく、分割仕込等により部分的に系に導入して存在させてもよい。 In the production method of the present invention, the organic base containing a nitrogen atom may be used alone or in combination of two or more. In the production method of the present invention, the organic base containing a nitrogen atom may be present in the system all at once, or may be partially introduced into the system by split charging or the like.
　本発明によれば、α，β－不飽和酸エステルである化合物４またはα－ハロエステルである化合物５が目的生成物として得られる。なお、本発明の製造方法では、化合物４および化合物５の両方が得られても、化合物４または化合物５の一方のみが得られてもよい。　化合物４は、化成品またはコーティング剤等のモノマー原料として用いられる。化合物５の脱塩化水素を実施すれば、化合物４として使用できる。
　　式（４）　ＣＨ２＝ＣＲＣ（Ｏ）ＯＱ
　　式（５）　ＣＨ３ＣＸＲＣ（Ｏ）ＯＱ
　上記式（４）および式（５）中、Ｒ、ＸおよびＱは上記定義の通りである。 According to the present invention, compound 4 which is an α, β-unsaturated acid ester or compound 5 which is an α-haloester is obtained as a target product. In the production method of the present invention, both compound 4 and compound 5 may be obtained, or only one of compound 4 or compound 5 may be obtained. Compound 4 is used as a raw material for a monomer such as a chemical product or a coating agent. If dehydrochlorination of compound 5 is carried out, it can be used as compound 4.
Formula (4) CH 2 = CRC (O) OQ
Formula (5) CH 3 CXRC (O) OQ
In the above formulas (4) and (5), R, X and Q are as defined above.
　上記化合物１、化合物２、および化合物３の反応は、上記窒素原子を含む有機塩基に加えて、非プロトン性極性溶剤の存在下で行われるのが好ましい。
　非プロトン性極性溶剤としては、例えばジメチルホルムアミド、ジメチルアセトアミド、γ－ブチロラクトン、γ－バレロラクトン、ε－カプロラクトン、ジメチルスルホキシド、テトラメチレンスルホキシド、１－メチル－２－ピロリドン、テトラヒドロフラン、ジメチル尿素、１，１，３，３－テトラメチル尿素、アセトニトリル、ジグライム等が挙げられる。 The reaction of Compound 1, Compound 2, and Compound 3 is preferably performed in the presence of an aprotic polar solvent in addition to the organic base containing the nitrogen atom.
Examples of the aprotic polar solvent include dimethylformamide, dimethylacetamide, γ-butyrolactone, γ-valerolactone, ε-caprolactone, dimethyl sulfoxide, tetramethylene sulfoxide, 1-methyl-2-pyrrolidone, tetrahydrofuran, dimethylurea, 1, 1,3,3-tetramethylurea, acetonitrile, diglyme and the like can be mentioned.
　化合物２の使用量に対して、化合物１の使用量が１～１０倍モルであるのが好ましく、１～７倍モルがより好ましく、１～５倍モルがさらに好ましい。化合物１の使用量が上記範囲内であれば、反応時に生じる副生成物の生成量が少なくなる。
　本発明において、化合物２の使用量に対して、化合物３の使用量が１～１０倍モルであるのが好ましく、１～５倍モルがより好ましく、１～３倍モルがさらに好ましい。化合物３の使用量が上記上限値であれば、副生成物の生成量が少なくなる。
　化合物２の使用量に対して、窒素原子を含む有機塩基の使用量が２倍モル以上であるのが好ましく、３倍モル以上がより好ましい。また、窒素原子を含む有機塩基の使用量は、化合物２の使用量に対して、通常、５倍モル以下である。窒素原子を含む有機塩基の使用量が２倍モル以上であれば、本発明の製造方法における目的物を化合物（４）とする場合に化学量論的に適量である。
　上記非プロトン性極性溶剤を用いる場合、化合物２の１ｍｏｌに対して、非プロトン性極性溶剤の使用量が０．０１～１００Ｌであるのが好ましく、０．１～１Ｌがより好ましい。 The amount of compound 1 used is preferably 1 to 10-fold mol, more preferably 1 to 7-fold mol, and even more preferably 1 to 5-fold mol based on the amount of compound 2. If the usage-amount of the compound 1 is in the said range, the production amount of the by-product produced at the time of reaction will decrease.
In the present invention, the amount of compound 3 used is preferably 1 to 10 times the mole, more preferably 1 to 5 times the mole, and still more preferably 1 to 3 times the mole of compound 2. If the usage-amount of the compound 3 is the said upper limit, the production amount of a by-product will decrease.
The amount of the organic base containing a nitrogen atom is preferably 2 times mol or more, more preferably 3 times mol or more with respect to the amount of compound 2 used. The amount of the organic base containing a nitrogen atom is usually 5 times or less the amount of compound 2 used. If the amount of the organic base containing a nitrogen atom is 2 times or more, it is a stoichiometrically appropriate amount when the target product in the production method of the present invention is the compound (4).
When the aprotic polar solvent is used, the amount of the aprotic polar solvent used is preferably 0.01 to 100 L, more preferably 0.1 to 1 L, relative to 1 mol of Compound 2.
　以下の反応機構に例示するように、化合物４は、１ポットで得られる。なお、以下の反応機構中、Ｂａｓｅは窒素原子を有する有機塩基を表し、ＭＭＡは化合物４の一態様であるメタクリル酸メチルを表す。また、以下の反応機構中、ＭＭＡの直前に得られる化合物は、化合物５の一態様である２－クロロ－２－メチルプロパン酸メチルである。
　このように、本発明の製造方法によれば、原料である化合物を段階的に反応させる従来製法と比較して、工程を簡略化できるので、製造コスト等を削減できる。 As illustrated in the reaction mechanism below, compound 4 is obtained in one pot. In the following reaction mechanism, Base represents an organic base having a nitrogen atom, and MMA represents methyl methacrylate which is one embodiment of Compound 4. In the following reaction mechanism, the compound obtained immediately before MMA is methyl 2-chloro-2-methylpropanoate which is one embodiment of compound 5.
As described above, according to the production method of the present invention, the manufacturing cost can be reduced because the process can be simplified as compared with the conventional production method in which the raw material compound is reacted stepwise.
Figure JPOXMLDOC01-appb-C000003
Figure JPOXMLDOC01-appb-C000003
　本発明の製造方法で得られた化合物５の脱塩化水素を実施すれば、化合物４が得られる。化合物５の脱塩化水素は、例えば、米国特許第２０１３６４８号明細書、米国特許第２１９９７７４号明細書、および、国際公開第２０１４／０３８４８９号等に記載される方法によって容易に実施できる。
　具体的には、国際公開第２０１４／０３８４８９号の段落００４３～００５３に記載の工程Ｂに基づいて実施されるのが好ましく、化合物５と塩基性化合物とを反応させる方法や、化合物５に光、超音波、マイクロ波などを照射する方法が挙げられる。
　該塩基性化合物としては、金属水酸化物、金属酸化物、金属炭酸塩、金属アルコキシド、金属アミド、アミン類が入手し易い点で好ましく、金属水酸化物、金属酸化物、金属炭酸塩、金属アルコキシド、アミン類がより好ましい。これらの化合物中の金属としては、リチウム、ナトリウム、カリウム、カルシウムおよびマグネシウム等が挙げられる。 When dehydrochlorination of compound 5 obtained by the production method of the present invention is carried out, compound 4 is obtained. The dehydrochlorination of Compound 5 can be easily carried out by the methods described in, for example, US Pat. No. 2013648, US Pat. No. 2,199,774, and International Publication No. 2014/038489.
Specifically, it is preferably carried out based on Step B described in paragraphs 0043 to 0053 of International Publication No. 2014/038489, a method of reacting Compound 5 with a basic compound, The method of irradiating with an ultrasonic wave, a microwave, etc. is mentioned.
As the basic compound, metal hydroxides, metal oxides, metal carbonates, metal alkoxides, metal amides, and amines are preferable because they are easily available. Metal hydroxides, metal oxides, metal carbonates, metals Alkoxides and amines are more preferred. Examples of the metal in these compounds include lithium, sodium, potassium, calcium, and magnesium.
　本発明の化合物４の製造方法における副生成物の１つとして、窒素原子を有する有機塩基に基づく副生成物が挙げられる。窒素原子を有する有機塩基に基づく副生成物は、具体的には、窒素原子を有する有機塩基のハロゲン化水素酸塩（例えば塩酸塩）である。
　窒素原子を有する有機塩基に基づく副生成物は、以下の反応機構に示すように、脱ハロゲン化水素（例えば脱塩化水素）させれば、窒素原子を有する有機塩基として再生できる。また、回収されたハロゲン化水素（例えば塩化水素）は、以下の反応機構に例示するように、本発明の化合物２の原料として再利用できる。このように、本発明の製造方法に使用する原料は、副生成物を用いて再生できるため、本発明の製造方法は工業的に非常に優れる。なお、以下の反応機構における「Ｂａｓｅ」は、窒素原子を有する有機塩基を意味する。 One of the by-products in the production method of the compound 4 of the present invention is a by-product based on an organic base having a nitrogen atom. A by-product based on an organic base having a nitrogen atom is specifically a hydrohalide salt (for example, hydrochloride) of an organic base having a nitrogen atom.
A by-product based on an organic base having a nitrogen atom can be regenerated as an organic base having a nitrogen atom by dehydrohalogenation (for example, dehydrochlorination) as shown in the following reaction mechanism. The recovered hydrogen halide (for example, hydrogen chloride) can be reused as a raw material for the compound 2 of the present invention, as exemplified in the following reaction mechanism. Thus, since the raw material used for the manufacturing method of this invention can be reproduced | regenerated using a by-product, the manufacturing method of this invention is very excellent industrially. “Base” in the following reaction mechanism means an organic base having a nitrogen atom.
Figure JPOXMLDOC01-appb-C000004
Figure JPOXMLDOC01-appb-C000004
　窒素原子を有する有機塩基は、担体に担持された状態で使用されてもよい。つまり、窒素原子を有する有機塩基が担持された担体を用いて上記化合物４の製造方法を実施した後、これを回収し、上述したように脱ハロゲン化水素（例えば脱塩化水素）させれば、担体に担持された窒素原子を有する有機塩基を再生して、再利用できる。
　上記担体としては、カーボンブラック、シリカ（例えば、コロイダルシリカ、フュームドシリカ、湿式シリカ、ケイ酸塩鉱物）、金属酸化物、金属チッ化物等の微粒子が挙げられる。窒素原子を有する有機塩基を担体に担持させる方法としては、日本国特開平０８－１５７５７０号公報を参照できる。 The organic base having a nitrogen atom may be used while being supported on a carrier. That is, after carrying out the production method of the compound 4 using a carrier on which an organic base having a nitrogen atom is supported, this is recovered and dehydrohalogenated (for example, dehydrochlorinated) as described above, An organic base having a nitrogen atom supported on a carrier can be regenerated and reused.
Examples of the carrier include fine particles such as carbon black, silica (for example, colloidal silica, fumed silica, wet silica, silicate mineral), metal oxide, and metal nitride. Japanese Patent Application Laid-Open No. 08-157570 can be referred to as a method for supporting an organic base having a nitrogen atom on a carrier.
　以下、実施例を挙げて本発明を詳細に説明する。ただし、本発明はこれらの実施例に限定されない。なお、例２７～２９は比較例である。
　後述する表中における各成分の配合量は、質量基準を示す。 Hereinafter, the present invention will be described in detail with reference to examples. However, the present invention is not limited to these examples. Examples 27 to 29 are comparative examples.
The compounding quantity of each component in the table | surface mentioned later shows a mass reference | standard.
［例１］
　アセトン（２．９ｇ、５０ｍｍｏｌ）、１，８－ジアザビシクロ［５．４．０］ウンデカ－７－エン（ＤＢＵ、５．０ｇ、３３ｍｍｏｌ）、メタノール（０．８０ｇ，２５ｍｍｏｌ）、内部標準の１，４－ジブロモベンゼン（０．１５ｇ、０．６４ｍｍｏｌ）およびアセトニトリル（５．０ｍＬ）を含む溶液に、０℃にて撹拌下、クロロホルム（１．２ｇ，１０ｍｍｏｌ）をゆっくり加えた後、５０℃にて１８時間撹拌した。さらに還流下（８０℃）、２４時間撹拌した後、２５℃にして得られた反応液を１，４－ジブロモベンゼンを内部標準として１ＨＮＭＲ分析した結果、メタクリル酸メチル（ＭＭＡ）と２－クロロ－２－メチルプロパン酸メチルの生成を確認した。また、ＭＭＡおよび２－クロロ－２－メチルプロパン酸メチルの反応収率はそれぞれ、クロロホルムを基準として６１ｍｏｌ％、７．８ｍｏｌ％であった。 [Example 1]
Acetone (2.9 g, 50 mmol), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU, 5.0 g, 33 mmol), methanol (0.80 g, 25 mmol), 1, Chloroform (1.2 g, 10 mmol) was slowly added to a solution containing 4-dibromobenzene (0.15 g, 0.64 mmol) and acetonitrile (5.0 mL) with stirring at 0 ° C., and then at 50 ° C. Stir for 18 hours. Further, after stirring for 24 hours under reflux (80 ° C.), the reaction solution obtained at 25 ° C. was analyzed by 1 HNMR using 1,4-dibromobenzene as an internal standard. As a result, methyl methacrylate (MMA) and 2-chloro Formation of methyl -2-methylpropanoate was confirmed. The reaction yields of MMA and methyl 2-chloro-2-methylpropanoate were 61 mol% and 7.8 mol% based on chloroform, respectively.
［例２～例２９］
　表１、表２および表３に示すように、塩基の種類、使用原料の種類、反応溶媒および反応条件の少なくとも１つを変更した以外は、例１と同様にして、例２～例２９を実施した。それぞれの例における生成物の反応収率を表１にまとめて示す。 [Example 2 to Example 29]
As shown in Table 1, Table 2 and Table 3, Examples 2 to 29 were carried out in the same manner as in Example 1 except that at least one of the type of base, the type of raw materials used, the reaction solvent and the reaction conditions was changed. Carried out. The reaction yield of the product in each example is summarized in Table 1.
　なお、略称で示す窒素原子を含む有機塩基の構造は以下の通りであり、アセトニトリル中でのｐＫＢＨとあわせて以下に示す。 The structure of the organic bases containing nitrogen atom indicated by abbreviations as follows, illustrated below in conjunction with pK BH in acetonitrile.
Figure JPOXMLDOC01-appb-C000005
Figure JPOXMLDOC01-appb-C000005
　表１における、化合物４および化合物５は、使用原料組み合せがＳ１～Ｓ１３である場合には順にメタクリル酸メチル、２－クロロ－２－メチルプロパン酸メチルであり、使用原料組み合せがＳ１４である場合には順にメタクリル酸エチル、２－クロロ－２－メチルプロパン酸エチルであり、使用原料組み合せがＳ１５である場合には順にメタクリル酸ｔｅｒｔ－ブチル、２－クロロ－２－メチルプロパン酸ｔｅｒｔ－ブチルであり、使用原料組み合せがＳ１６である場合には順にＣＨ２＝Ｃ（ＣＨ３）Ｃ（Ｏ）ＯＣＨ２ＣＦ３、ＣＨ３ＣＣｌ（ＣＨ３）Ｃ（Ｏ）ＯＣＨ２ＣＦ３であり、使用原料組み合せがＳ１７である場合には順にＣＨ２＝Ｃ（ＣＨ３）Ｃ（Ｏ）ＯＣＨ２ＣＨ２（ＣＦ２）６Ｆ、ＣＨ３ＣＣｌ（ＣＨ３）Ｃ（Ｏ）ＯＣＨ２ＣＨ２（ＣＦ２）６Ｆである。
　表１における、反応生成物である化合物４および化合物５の反応収率はクロロホルムを基準とし、合計の値は化合物４と化合物５の反応収率の合計値である。 In Table 1, compound 4 and compound 5 are methyl methacrylate and methyl 2-chloro-2-methylpropanoate in order when the used raw material combination is S1 to S13, and when the used raw material combination is S14. Are ethyl methacrylate and ethyl 2-chloro-2-methylpropanoate in this order, and when the raw material combination is S15, tert-butyl methacrylate and tert-butyl 2-chloro-2-methylpropanoate are in order. When the combination of raw materials used is S16, CH 2 = C (CH 3 ) C (O) OCH 2 CF 3 and CH 3 CCl (CH 3 ) C (O) OCH 2 CF 3 are used in this order. There sequentially CH 2 = C (CH 3) in the case of S17 C (O) OCH 2 CH 2 (CF 2) 6 F, CH 3 CCl (CH ) C (O) OCH 2 CH 2 (CF 2) a 6 F.
In Table 1, the reaction yields of compound 4 and compound 5, which are reaction products, are based on chloroform, and the total value is the total reaction yield of compound 4 and compound 5.
　表２における使用原料組み合せにおけるそれぞれの値は、クロロホルム１ｍｏｌに対する、それぞれの原料のｍｏｌ比率である。また、表２における使用原料組み合せ（Ｓ１１）における「Ｓｏｌｖ．」とは、クロロホルム１ｍｏｌに対して、８ｍｏｌ倍以上の原料を用いたことを意味する。
　また、表３における反応条件Ｃ５は、５０℃にて１８時間反応させた後に、８０℃にて２４時間反応させたことを意味する。 Each value in the combination of raw materials used in Table 2 is the molar ratio of each raw material to 1 mol of chloroform. Moreover, "Solv." In the used raw material combination (S11) in Table 2 means that 8 mol times or more of raw material was used with respect to 1 mol of chloroform.
Reaction condition C5 in Table 3 means that the reaction was carried out at 50 ° C. for 18 hours and then at 80 ° C. for 24 hours.
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
　表１に示す通り、窒素原子を含む有機塩基の存在下、化合物１と化合物２と化合物３とを反応させると、化合物４および／または化合物５が短工程（ワンポット）で得られた（例１～例２６）。一方、窒素原子を含む有機塩基を用いていない例２７～例２９によれば、化合物４および化合物５が得られなかった。 As shown in Table 1, when Compound 1, Compound 2 and Compound 3 were reacted in the presence of an organic base containing a nitrogen atom, Compound 4 and / or Compound 5 were obtained in a short process (one pot) (Example 1). To Example 26). On the other hand, according to Examples 27 to 29 using no organic base containing a nitrogen atom, compounds 4 and 5 were not obtained.
［例３０］
　アセトン（７５ｍｇ、１３ｍｍｏｌ）、ｔ－Ｂｕ－Ｐ１（２．０ｇ、８．４ｍｍｏｌ）、メタノール（０．１３ｇ，４．０ｍｍｏｌ）、内部標準の１，４－ジブロモベンゼン（３７ｍｇ、０．１５ｍｍｏｌ）およびアセトニトリル（６．９ｇ）を含む溶液に、０℃にて撹拌下、クロロホルム（０．３０ｇ，２．５ｍｍｏｌ）をゆっくり加えた後、５０℃にて２０時間撹拌した。さらにＤＢＵ（０．７６ｇ、５．０ｍｍｏｌ）をゆっくり加えたのち、還流下（８０℃）、２６時間撹拌した後、２５℃にして得られた反応液を１，４－ジブロモベンゼンを内部標準として１ＨＮＭＲ分析した結果、メタクリル酸メチルと２－クロロ－２－メチルプロパン酸メチルの生成を確認した。また、ＭＭＡおよび２－クロロ－２－メチルプロパン酸メチルの反応収率はそれぞれ、クロロホルムを基準として７８ｍｏｌ％、２．９ｍｏｌ％であった。 [Example 30]
Acetone (75 mg, 13 mmol), t-Bu-P 1 (2.0 g, 8.4 mmol), methanol (0.13 g, 4.0 mmol), internal standard 1,4-dibromobenzene (37 mg, 0.15 mmol) Then, chloroform (0.30 g, 2.5 mmol) was slowly added to a solution containing acetonitrile (6.9 g) with stirring at 0 ° C., followed by stirring at 50 ° C. for 20 hours. Further, DBU (0.76 g, 5.0 mmol) was slowly added, and the mixture was stirred at reflux (80 ° C.) for 26 hours, and then the reaction solution obtained at 25 ° C. was converted to 1,4-dibromobenzene as an internal standard. As a result of 1 HNMR analysis, formation of methyl methacrylate and methyl 2-chloro-2-methylpropanoate was confirmed. The reaction yields of MMA and methyl 2-chloro-2-methylpropanoate were 78 mol% and 2.9 mol%, respectively, based on chloroform.
［例３１］
　２－クロロ－２－メチルプロパン酸メチル（２．５８ｇ、１９ｍｍｏｌ）、内部標準の１，４－ジブロモベンゼン（０．１１７ｇ、０．５０ｍｍｏｌ）のアセトニトリル（８．０ｍＬ）溶液に、攪拌しながら１，８－ジアザビシクロ［５．４．０］ウンデカ－７－エン（ＤＢＵ、３．２１ｇ、２１ｍｍｏｌ）をゆっくり加えた。反応混合物を１３時間還流下に反応させた。１Ｈ－ＮＭＲ分析により、メタクリル酸メチル（ＭＭＡ）の生成を確認し、反応収率は２－クロロ－２－メチルプロパン酸メチルを基準として９７ｍｏｌ％であった。 [Example 31]
To a solution of methyl 2-chloro-2-methylpropanoate (2.58 g, 19 mmol), 1,4-dibromobenzene (0.117 g, 0.50 mmol) as an internal standard in acetonitrile (8.0 mL) while stirring, 1 , 8-diazabicyclo [5.4.0] undec-7-ene (DBU, 3.21 g, 21 mmol) was added slowly. The reaction mixture was reacted under reflux for 13 hours. The formation of methyl methacrylate (MMA) was confirmed by 1 H-NMR analysis, and the reaction yield was 97 mol% based on methyl 2-chloro-2-methylpropanoate.
［例３２～例３３］
　表４および表５に示すように、塩基の種類、使用原料の種類、反応溶媒および反応条件の少なくとも１つを変更した以外は、例１と同様にして、例３２～例３３を実施した。
　それぞれの例における生成物の反応収率を表４にまとめて示す。
　表４における、反応生成物である化合物４および化合物５の反応収率はクロロホルム（例３２ではブロモホルム）を基準とし、合計の値は化合物４と化合物５の反応収率の合計値である。
　表５における使用原料組み合せにおけるそれぞれの値は、クロロホルム１ｍｏｌ（例３２ではブロモホルム１ｍｏｌ）に対する、それぞれの原料のｍｏｌ比率である。
　また、表４における反応条件Ｃ５は、５０℃にて１８時間反応させた後に、８０℃にて２４時間反応させたことを意味する。 [Examples 32 to 33]
As shown in Tables 4 and 5, Examples 32 to 33 were carried out in the same manner as Example 1 except that at least one of the type of base, the type of raw material used, the reaction solvent and the reaction conditions was changed.
The reaction yield of the product in each example is summarized in Table 4.
In Table 4, the reaction yields of compound 4 and compound 5 which are reaction products are based on chloroform (bromoform in Example 32), and the total value is the total reaction yield of compound 4 and compound 5.
Each value in the used raw material combinations in Table 5 is the molar ratio of each raw material to 1 mol of chloroform (1 mol of bromoform in Example 32).
Reaction condition C5 in Table 4 means that the reaction was carried out at 50 ° C. for 18 hours and then at 80 ° C. for 24 hours.
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
　本発明を詳細に、また特定の実施態様を参照して説明したが、本発明の精神と範囲を逸脱することなく、様々な変更や修正を加えることができることは、当業者にとって明らかである。
　本出願は、２０１７年３月２日出願の日本特許出願２０１７－０３９５１２に基づくものであり、その内容はここに参照として取り込まれる。 Although the present invention has been described in detail and with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention.
This application is based on Japanese Patent Application No. 2017-039512 filed on Mar. 2, 2017, the contents of which are incorporated herein by reference.

Claims (13)

  1. 　窒素原子を含む有機塩基の存在下、下式（１）で表される化合物と、下式（２）で表される化合物と、下式（３）で表される化合物とを反応させて下式（４）で表される化合物または下式（５）で表される化合物を得る、下式（４）で表される化合物または下式（５）で表される化合物の製造方法。
    　式（１）　ＣＨ３Ｃ（Ｏ）Ｒ
    　式（２）　ＣＨＸ３
    　式（３）　ＱＯＨ
    　式（４）　ＣＨ２＝ＣＲＣ（Ｏ）ＯＱ
    　式（５）　ＣＨ３ＣＸＲＣ（Ｏ）ＯＱ
    　式中の記号は、以下の意味を表す。
    　Ｒは、炭素数１～１０のアルキル基もしくはアリール基、炭素数１～１０のヘテロ原子を含むアルキル基もしくはアリール基、または水素原子を表す。
    　Ｘはハロゲン原子を表す。
    　Ｑは、炭素数１～２０の１価有機基を表す。     In the presence of an organic base containing a nitrogen atom, the compound represented by the following formula (1), the compound represented by the following formula (2), and the compound represented by the following formula (3) are reacted: A method for producing a compound represented by the following formula (4) or a compound represented by the following formula (5), wherein the compound represented by the formula (4) or the compound represented by the following formula (5) is obtained.
    Formula (1) CH 3 C (O) R
    Formula (2) CHX 3
    Formula (3) QOH
    Formula (4) CH 2 = CRC (O) OQ
    Formula (5) CH 3 CXRC (O) OQ
    The symbols in the formula represent the following meanings.
    R represents an alkyl group or aryl group having 1 to 10 carbon atoms, an alkyl group or aryl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom.
    X represents a halogen atom.
    Q represents a monovalent organic group having 1 to 20 carbon atoms.
  2. 　窒素原子を含む有機塩基の存在下、下式（１－１）で表される化合物と下式（２－１）で表される化合物と下式（３）で表される化合物とを反応させて下式（４－１）で表される化合物または下式（５－１）で表される化合物を得る、請求項１に記載の製造方法。
    　式（１－１）　ＣＨ３Ｃ（Ｏ）Ｒ´
    　式（２－１）　ＣＨＣｌ３
    　式（３）　ＱＯＨ
    　式（４－１）　ＣＨ２＝ＣＲ´Ｃ（Ｏ）ＯＱ
    　式（５－１）　ＣＨ３ＣＣｌＲ´Ｃ（Ｏ）ＯＱ
    　式中の記号は、以下の意味を表す。
    　Ｒ´は、炭素数１～１０のアルキル基、炭素数１～１０のヘテロ原子を含むアルキル基、または水素原子を表す。
    　Ｑは、炭素数１～２０の１価有機基を表す。     In the presence of an organic base containing a nitrogen atom, a compound represented by the following formula (1-1) is reacted with a compound represented by the following formula (2-1) and a compound represented by the following formula (3). The production method according to claim 1, wherein the compound represented by the following formula (4-1) or the compound represented by the following formula (5-1) is obtained.
    Formula (1-1) CH 3 C (O) R ′
    Formula (2-1) CHCl 3
    Formula (3) QOH
    Formula (4-1) CH 2 = CR′C (O) OQ
    Formula (5-1) CH 3 CClR′C (O) OQ
    The symbols in the formula represent the following meanings.
    R ′ represents an alkyl group having 1 to 10 carbon atoms, an alkyl group containing a hetero atom having 1 to 10 carbon atoms, or a hydrogen atom.
    Q represents a monovalent organic group having 1 to 20 carbon atoms.
  3. 　前記窒素原子を含む有機塩基が、水素原子と結合した窒素原子を有しない、請求項１または２に記載の製造方法。 The production method according to claim 1 or 2, wherein the organic base containing a nitrogen atom does not have a nitrogen atom bonded to a hydrogen atom.
  4. 　前記窒素原子を含む有機塩基のアセトニトリル中でのｐＫＢＨが、２０以上である、請求項１～３のいずれか１項に記載の製造方法。 PK BH in acetonitrile in an organic base containing a nitrogen atom is 20 or more, the production method according to any one of claims 1 to 3.
  5. 　前記窒素原子を含む有機塩基が、ホスファゼン構造を有する有機塩基、グアニジン構造を有する有機塩基、アミジン構造を有する有機塩基、またはプロアザホスファトラン構造を有する有機塩基である、請求項１～４のいずれか１項に記載の製造方法。 The organic base containing a nitrogen atom is an organic base having a phosphazene structure, an organic base having a guanidine structure, an organic base having an amidine structure, or an organic base having a proazaphosphatran structure. The manufacturing method of any one of Claims.
  6. 　ＲまたはＲ´が、メチル基、エチル基、トリフルオロメチル基、または水素原子である、請求項１～５のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 5, wherein R or R 'is a methyl group, an ethyl group, a trifluoromethyl group, or a hydrogen atom.
  7. 　Ｑが、炭素数１～２０の１価炭化水素基またはヘテロ原子を有する炭素数１～２０の１価炭化水素基である、請求項１～６のいずれか１項に記載の製造方法。 7. The production method according to any one of claims 1 to 6, wherein Q is a monovalent hydrocarbon group having 1 to 20 carbon atoms or a monovalent hydrocarbon group having 1 to 20 carbon atoms having a hetero atom.
  8. 　前記式（２）で表される化合物の使用量に対して、前記式（１）で表される化合物の使用量が１～１０倍モルである、請求項１～７のいずれか１項に記載の製造方法。 The amount of the compound represented by the formula (1) is 1 to 10 times mol of the amount of the compound represented by the formula (2), according to any one of claims 1 to 7. The manufacturing method as described.
  9. 　前記式（２）で表される化合物の使用量に対して、前記式（３）で表される化合物の使用量が１～１０倍モルである、請求項１～８のいずれか１項に記載の製造方法。 The amount of the compound represented by the formula (3) is 1 to 10 times the amount of the compound represented by the formula (2) according to any one of claims 1 to 8. The manufacturing method as described.
  10. 　前記式（２）で表される化合物の使用量に対して、前記窒素原子を含む有機塩基の使用量が２倍モル以上である、請求項１～９のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 9, wherein the amount of the organic base containing a nitrogen atom is 2 times or more by mole with respect to the amount of the compound represented by the formula (2). .
  11. 　前記反応が、非プロトン性極性溶剤の存在下で行われる、請求項１～１０のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 10, wherein the reaction is carried out in the presence of an aprotic polar solvent.
  12. 　前記式（４）で表される化合物を得る、請求項１～１１のいずれか１項に記載の製造方法。 The production method according to any one of claims 1 to 11, wherein the compound represented by the formula (4) is obtained.
  13. 　請求項１～１１のいずれか１項に記載の製造方法で（５）で表される化合物を得て、該化合物を脱塩化水素させて、式（４）で表される化合物を得る、式（４）で表される化合物の製造方法。 A compound represented by formula (5) is obtained by the production method according to any one of claims 1 to 11, and the compound represented by formula (4) is obtained by dehydrochlorinating the compound. (4) The manufacturing method of the compound represented.
PCT/JP2018/008169 2017-03-02 2018-03-02 PRODUCTION METHOD FOR α,β-UNSATURATED ACID ESTER OR α-HALOESTER WO2018159846A1 (en)

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