JP2013014534A - Benzoylformic acid compound and method for producing the same - Google Patents
Benzoylformic acid compound and method for producing the same Download PDFInfo
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- JP2013014534A JP2013014534A JP2011147853A JP2011147853A JP2013014534A JP 2013014534 A JP2013014534 A JP 2013014534A JP 2011147853 A JP2011147853 A JP 2011147853A JP 2011147853 A JP2011147853 A JP 2011147853A JP 2013014534 A JP2013014534 A JP 2013014534A
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- 0 *c1cc(S*)c(*)cc1C(C(O*)=O)=O Chemical compound *c1cc(S*)c(*)cc1C(C(O*)=O)=O 0.000 description 3
- JPEADVHWRBGOJV-UHFFFAOYSA-N CCCCC(CC)CSc1c(C)cc(C(C(Cl)=O)=O)c(C)c1 Chemical compound CCCCC(CC)CSc1c(C)cc(C(C(Cl)=O)=O)c(C)c1 JPEADVHWRBGOJV-UHFFFAOYSA-N 0.000 description 1
- DOQLXQXVVDIDGO-UHFFFAOYSA-N CCCCC(CC)CSc1c(C)cc(C(C(O)=O)=O)c(C)c1 Chemical compound CCCCC(CC)CSc1c(C)cc(C(C(O)=O)=O)c(C)c1 DOQLXQXVVDIDGO-UHFFFAOYSA-N 0.000 description 1
- CZYYERANIHHAMI-UHFFFAOYSA-N CCCCC(CC)CSc1c(C)cc(C(C(OCC)=O)=O)c(C)c1 Chemical compound CCCCC(CC)CSc1c(C)cc(C(C(OCC)=O)=O)c(C)c1 CZYYERANIHHAMI-UHFFFAOYSA-N 0.000 description 1
- OWZFULPEVHKEKS-UHFFFAOYSA-N CCOC(C(Cl)=O)=O Chemical compound CCOC(C(Cl)=O)=O OWZFULPEVHKEKS-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
本発明は、医薬、農薬、又はその中間体、電子材料中間体、光重合開始剤等として有用なベンゾイルギ酸化合物、及びその製造方法に関する。 The present invention relates to a benzoylformic acid compound useful as a pharmaceutical, agricultural chemical, or an intermediate thereof, an electronic material intermediate, a photopolymerization initiator, and the like, and a production method thereof.
ベンゾイルギ酸化合物は、医薬、農薬、又はその中間体、電子材料中間体、光重合開始剤等として有用であることが知られている。特許文献１には、農業用殺菌剤の中間体として有用なフェニルグリオキシル酸エステルが記載されている。特許文献２には、光重合開始剤として、パラ位にメチルチオ基を有するフェニルグリオキシル酸及びその誘導体が記載されている。 Benzoyl formic acid compounds are known to be useful as pharmaceuticals, agricultural chemicals, or intermediates thereof, electronic material intermediates, photopolymerization initiators, and the like. Patent Document 1 describes phenylglyoxylic acid esters useful as intermediates for agricultural fungicides. Patent Document 2 describes phenylglyoxylic acid having a methylthio group at the para position and a derivative thereof as a photopolymerization initiator.
本発明の目的は、医薬、農薬、又はその中間体、電子材料中間体、光重合開始剤等として有用な新規のベンゾイルギ酸化合物を提供することにある。
本発明の他の目的は、新規のベンゾイルギ酸化合物の製造方法を提供することにある。
An object of the present invention is to provide a novel benzoylformic acid compound useful as a medicine, agricultural chemical, or an intermediate thereof, an electronic material intermediate, a photopolymerization initiator, and the like.
Another object of the present invention is to provide a method for producing a novel benzoylformic acid compound.
本発明者は、上記課題を解決するため鋭意検討した結果、塩基の存在下、アルキル置換ベンゼンチオールに炭素数４〜１０のハロゲン化アルキルを反応させて得られる化合物にグリオキシル基を導入すると、新規のベンゾイルギ酸化合物が得られることを見いだした。本発明はこれらの知見に基づいて完成させたものである。 As a result of intensive studies to solve the above problems, the present inventor introduced a glyoxyl group into a compound obtained by reacting an alkyl-substituted benzenethiol with an alkyl halide having 4 to 10 carbon atoms in the presence of a base. It was found that a benzoylformic acid compound was obtained. The present invention has been completed based on these findings.
すなわち、本発明は下記式（１）
で表されるベンゾイルギ酸化合物を提供する。
That is, the present invention provides the following formula (1):
The benzoyl formic acid compound represented by these is provided.
本発明は、また、下記式（２）
で表される化合物と、下記式（３）
で表されるグリオキシル酸誘導体を、酸触媒の存在下で反応させる工程を経て、下記式（１）
で表されるベンゾイルギ酸化合物を得るベンゾイルギ酸化合物の製造方法を提供する。
The present invention also provides the following formula (2):
And a compound represented by the following formula (3)
Through the step of reacting the glyoxylic acid derivative represented by the following formula (1):
The manufacturing method of the benzoyl formate compound which obtains the benzoyl formate compound represented by this is provided.
本発明は、さらにまた、下記式（２）
で表される化合物を提供する。
The present invention further provides the following formula (2):
The compound represented by these is provided.
本発明にかかるベンゾイルギ酸化合物の製造方法によれば、効率よく且つ簡便に、上記式（１）で表される新規のベンゾイルギ酸化合物を合成することができる。そして、得られた上記式（１）で表されるベンゾイルギ酸化合物は、医薬、農薬、又はその中間体、電子材料中間体、光重合開始剤等として有用である。 According to the method for producing a benzoylformate compound according to the present invention, a novel benzoylformate compound represented by the above formula (1) can be synthesized efficiently and simply. The obtained benzoylformic acid compound represented by the above formula (1) is useful as a medicine, agricultural chemical, or an intermediate thereof, an electronic material intermediate, a photopolymerization initiator, and the like.
［ベンゾイルギ酸化合物］
本発明にかかるベンゾイルギ酸化合物は上記式（１）で表される。式中、Ｒ1は炭素数１〜３の脂肪族炭化水素基、Ｒ2は水素原子又は炭素数１〜３の脂肪族炭化水素基若しくは脂環式炭化水素基、Ｒ3は炭素数４〜１０の脂肪族炭化水素基若しくは脂環式炭化水素基を示す。Ａはヒドロキシル基、ハロゲン原子、又はＯＲ4（Ｒ4は炭素数１〜６の脂肪族炭化水素基）を示す。
[Benzoylformic acid compound]
The benzoylformic acid compound according to the present invention is represented by the above formula (1). In the formula, R 1 is an aliphatic hydrocarbon group having 1 to 3 carbon atoms, R 2 is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 3 carbon atoms or an alicyclic hydrocarbon group, and R 3 is 4 to 4 carbon atoms. 10 aliphatic hydrocarbon groups or alicyclic hydrocarbon groups are shown. A represents a hydroxyl group, a halogen atom, or OR 4 (R 4 is an aliphatic hydrocarbon group having 1 to 6 carbon atoms).
Ｒ1は炭素数１〜３の脂肪族炭化水素基を示し、例えば、メチル、エチル、プロピル、イソプロピル基等の直鎖状又は分岐鎖状のＣ1-3アルキル基；ビニル、１−プロペニル、アリル基等の直鎖状又は分岐鎖状のＣ2-3アルケニル基；エチニル、１−プロピニル、２−プロピニル基等の直鎖状又は分岐鎖状のＣ2-3アルキニル基等が挙げられる。本発明におけるＲ1としては、なかでも直鎖状又は分岐鎖状のＣ1-3アルキル基が好ましい。 R 1 represents an aliphatic hydrocarbon group having 1 to 3 carbon atoms, for example, a linear or branched C 1-3 alkyl group such as methyl, ethyl, propyl, isopropyl group; vinyl, 1-propenyl, Examples include linear or branched C 2-3 alkenyl groups such as an allyl group; linear or branched C 2-3 alkynyl groups such as ethynyl, 1-propynyl, and 2-propynyl groups. In the present invention, R 1 is preferably a linear or branched C 1-3 alkyl group.
Ｒ2は水素原子又は炭素数１〜３の脂肪族炭化水素基若しくは脂環式炭化水素基を示す。炭素数１〜３の脂肪族炭化水素基の例としては上記Ｒ1における炭素数１〜３の脂肪族炭化水素基の例と同様の例を挙げることができる。また、炭素数１〜３の脂環式炭化水素基の例としては、シクロプロピル基、シクロプロペニル基等を挙げることができる。本発明におけるＲ2としては、なかでも炭素数１〜３の脂肪族炭化水素基が好ましく、特に、直鎖状又は分岐鎖状のＣ1-3アルキル基が好ましい。 R 2 represents a hydrogen atom, an aliphatic hydrocarbon group having 1 to 3 carbon atoms or an alicyclic hydrocarbon group. Examples of the aliphatic hydrocarbon group having 1 to 3 carbon atoms may be the same examples and examples of the aliphatic hydrocarbon group having 1 to 3 carbon atoms in the R 1. Examples of the alicyclic hydrocarbon group having 1 to 3 carbon atoms include a cyclopropyl group and a cyclopropenyl group. As R 2 in the present invention, an aliphatic hydrocarbon group having 1 to 3 carbon atoms is preferable, and a linear or branched C 1-3 alkyl group is particularly preferable.
Ｒ3は炭素数４〜１０の脂肪族炭化水素基若しくは脂環式炭化水素基を示す。炭素数４〜１０の脂肪族炭化水素基としては、例えば、ブチル、イソブチル、sec−ブチル、tert−ブチル、１−メチルブチル、２−メチルブチル、３−メチルブチル、１，２−ジメチルブチル、１，３−ジメチルブチル、２，３−ジメチルブチル、１，２，３−トリメチルブチル、アミル、イソアミル、ヘキシル、イソヘキシル、２−エチルヘキシル、３−エチルヘキシル、４−エチルヘキシル、ヘプチル、イソヘプチル、オクチル、イソオクチル、カプリル、ノニル、デシル基等の直鎖状又は分岐鎖状アルキル基；１−ブテニル、２−ブテニル、３−ブテニル、２−メチル−１−プロペニル、２−メチルアリル、１−メチル−１−プロペニル、１−メチルアリル、１，１−ジメチルビニル、１−ペンテニル、２−ペンテニル、３−ペンテニル、４−ペンテニル、３−メチル−１−ブテニル、３−メチル−２−ブテニル、３−メチル−３−ブテニル、２−メチル−１−ブテニル、２−メチル−２−ブテニル、２−メチル−３−ブテニル、１−メチル−１−ブテニル、１−メチル−２−ブテニル、１−メチル−３−ブテニル、１，１−ジメチルアリル、１，２−ジメチル−１−プロペニル、１，２−ジメチル−２−プロペニル、１−エチル−１−プロペニル、１−エチル−２−プロペニル、１−ヘキセニル、２−ヘキセニル、３−ヘキセニル、３−メチル−１−ブテニル、４−ヘキセニル、５−ヘキセニル、１，１−ジメチル−１−ブテニル、１，１−ジメチル−２−ブテニル、１，１−ジメチル−３−ブテニル、３，３−ジメチル−１−ブテニル、１−メチル−１−ペンテニル、１−メチル−２−ペンテニル、１−メチル−３−ペンテニル、１−メチル−４−ペンテニル、４−メチル−１−ペンテニル、４−メチル−２−ペンテニル、４−メチル−３−ペンテニル基等の直鎖状又は分岐鎖状アルケニル基等を挙げることができる。 R 3 represents an aliphatic hydrocarbon group having 4 to 10 carbon atoms or an alicyclic hydrocarbon group. Examples of the aliphatic hydrocarbon group having 4 to 10 carbon atoms include butyl, isobutyl, sec-butyl, tert-butyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylbutyl, 1,3 -Dimethylbutyl, 2,3-dimethylbutyl, 1,2,3-trimethylbutyl, amyl, isoamyl, hexyl, isohexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, heptyl, isoheptyl, octyl, isooctyl, capryl, Linear or branched alkyl groups such as nonyl and decyl groups; 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 2-methylallyl, 1-methyl-1-propenyl, 1- Methylallyl, 1,1-dimethylvinyl, 1-pentenyl, 2-pentenyl, 3-pentenyl 4-pentenyl, 3-methyl-1-butenyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 2-methyl-3 -Butenyl, 1-methyl-1-butenyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 1,1-dimethylallyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl- 2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 3-methyl-1-butenyl, 4-hexenyl, 5-hexenyl, 1, 1-dimethyl-1-butenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 1-methyl-1-pentenyl, 1- Linear chain such as til-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 4-methyl-1-pentenyl, 4-methyl-2-pentenyl, 4-methyl-3-pentenyl Or a branched alkenyl group.
Ｒ3における炭素数４〜１０の脂環式炭化水素基としては、例えば、シクロブチル、シクロペンチル、シクロヘキシル、シクロオクチル基などの４〜１０員（好ましくは５〜６員）のシクロアルキル基；シクロブテニル、シクロペンテニル、シクロヘキセニル基などの４〜１０員（好ましくは５〜６員）のシクロアルケニル基などの単環の脂環式炭化水素基；アダマンタン環、パーヒドロインデン環、デカリン環、トリシクロデカン環、ノルボルナン環、ノルボルネン環など２〜３環程度の有橋脂環などを有する有橋脂環式炭化水素基（橋かけ環炭化水素基）等を挙げることができる。 Examples of the alicyclic hydrocarbon group having 4 to 10 carbon atoms in R 3 include 4 to 10-membered (preferably 5 to 6-membered) cycloalkyl groups such as cyclobutyl, cyclopentyl, cyclohexyl, and cyclooctyl groups; cyclobutenyl, Monocyclic alicyclic hydrocarbon groups such as 4-10 membered (preferably 5-6 membered) cycloalkenyl groups such as cyclopentenyl and cyclohexenyl groups; adamantane ring, perhydroindene ring, decalin ring, tricyclodecane Examples thereof include a bridged alicyclic hydrocarbon group (bridged hydrocarbon group) having about 2 to 3 rings such as a ring, a norbornane ring and a norbornene ring.
本発明におけるＲ3としては、なかでも、炭素数４〜１０の脂肪族炭化水素基が好ましく、特に、炭素数４〜１０の分岐鎖状アルキル基が好ましい。 As R 3 in the present invention, an aliphatic hydrocarbon group having 4 to 10 carbon atoms is preferable, and a branched alkyl group having 4 to 10 carbon atoms is particularly preferable.
Ｒ4は炭素数１〜６の脂肪族炭化水素基を示す。炭素数１〜６の脂肪族炭化水素基としては、例えば、メチル、エチル、プロピル、イソプロピル、ブチル、イソブチル、ペンチル、ヘプチル、イソヘプチル基等の直鎖状又は分岐鎖状のアルキル基；ビニル、１−プロペニル、アリル基等の直鎖状又は分岐鎖状のアルケニル基；エチニル、１−プロピニル、２−プロピニル基等の直鎖状又は分岐鎖状のアルキニル基等が挙げられる。本発明におけるＲ4としては、なかでも直鎖状又は分岐鎖状のアルキル基（特に、炭素数１〜３の直鎖状アルキル基）が好ましい。 R 4 represents an aliphatic hydrocarbon group having 1 to 6 carbon atoms. Examples of the aliphatic hydrocarbon group having 1 to 6 carbon atoms include linear or branched alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, heptyl, and isoheptyl groups; vinyl, 1 -Linear or branched alkenyl groups such as propenyl and allyl groups; linear or branched alkynyl groups such as ethynyl, 1-propynyl and 2-propynyl groups. R 4 in the present invention is preferably a linear or branched alkyl group (particularly a linear alkyl group having 1 to 3 carbon atoms).
本発明における式（１）で表されるベンゾイルギ酸化合物の具体例としては、下記化合物等を挙げることができる。
［ベンゾイルギ酸化合物の製造方法］
上記式（１）で表されるベンゾイルギ酸化合物は、上記式（２）で表される化合物と、上記式（３）で表されるグリオキシル酸誘導体とを、酸触媒の存在下で反応させる工程を経て合成することができる。
[Method for producing benzoylformic acid compound]
The benzoylformic acid compound represented by the above formula (1) is a step of reacting the compound represented by the above formula (2) with the glyoxylic acid derivative represented by the above formula (3) in the presence of an acid catalyst. It can be synthesized via.
上記式（２）中、Ｒ1は炭素数１〜３の脂肪族炭化水素基、Ｒ2は水素原子又は炭素数１〜３の脂肪族炭化水素基若しくは脂環式炭化水素基、Ｒ3は炭素数４〜１０の脂肪族炭化水素基若しくは脂環式炭化水素基を示す。 In the above formula (2), R 1 is an aliphatic hydrocarbon group having 1 to 3 carbon atoms, R 2 is a hydrogen atom, an aliphatic hydrocarbon group having 1 to 3 carbon atoms or an alicyclic hydrocarbon group, and R 3 is An aliphatic hydrocarbon group having 4 to 10 carbon atoms or an alicyclic hydrocarbon group is shown.
式（２）中のＲ1、Ｒ2、Ｒ3は、上記式（１）中のＲ1、Ｒ2、Ｒ3に対応する。 R 1, R 2, R 3 in the formula (2) corresponds to R 1, R 2, R 3 in the formula (1).
式（２）で表される化合物の具体例としては、下記化合物を挙げることができる。
上記式（２）で表される化合物は、例えば、下記式（４）
で表される化合物に、塩基の存在下で、下記式（５）
Ｒ3−Ｘ' （５）
（式中、Ｒ3は上記に同じ。Ｘ'はハロゲン原子を示す）
で表される化合物を反応させることによりチオール基をチオエーテル化して合成することができる。
The compound represented by the above formula (2) is, for example, the following formula (4).
In the presence of a base, the compound represented by the following formula (5)
R 3 -X ′ (5)
(Wherein R 3 is the same as above, X ′ represents a halogen atom)
Can be synthesized by thioether-converting the thiol group.
Ｘ'はハロゲン原子を示し、例えば、塩素原子、臭素原子、ヨウ素原子などを挙げることができる。 X ′ represents a halogen atom, and examples thereof include a chlorine atom, a bromine atom, and an iodine atom.
塩基としては、例えば、アルカリ金属のギ酸塩、酢酸塩、プロピオン酸塩、安息香酸塩、リン酸塩、炭酸塩、又は炭酸水素塩等を挙げることができる。本発明においては、なかでも、炭酸ナトリウム、炭酸カリウム等のアルカリ金属の炭酸塩等の弱塩基を使用することが好ましい。塩基の使用量としては、例えば、上記式（４）で表される化合物１モルに対して、０．１〜５モル程度、好ましくは０．５〜２モル程度である。また、前記弱塩基と共に、水酸化ナトリウム、水酸化カリウムなどの強塩基を使用してもよい。水酸化ナトリウム、水酸化カリウムなどの強塩基を併用する場合、その使用量としては、上記式（４）で表される化合物１モルに対して、０．１〜５モル程度、好ましくは０．５〜３モル程度である。 Examples of the base include alkali metal formate, acetate, propionate, benzoate, phosphate, carbonate, bicarbonate, and the like. In the present invention, it is particularly preferable to use a weak base such as an alkali metal carbonate such as sodium carbonate or potassium carbonate. As the usage-amount of a base, it is about 0.1-5 mol with respect to 1 mol of compounds represented by the said Formula (4), Preferably it is about 0.5-2 mol. Moreover, you may use strong bases, such as sodium hydroxide and potassium hydroxide, with the said weak base. When a strong base such as sodium hydroxide or potassium hydroxide is used in combination, the amount used is about 0.1 to 5 mol, preferably about 0.1 mol, per 1 mol of the compound represented by the above formula (4). About 5 to 3 moles.
上記式（４）で表される化合物と式（５）で表される化合物の反応は、溶媒の存在下又は非存在下で行われる。前記溶媒としては、例えば、ヘキサン、ヘプタン、オクタンなどの脂肪族炭化水素；シクロヘキサンなどの脂環式炭化水素；ベンゼン、トルエン、キシレン、エチルベンゼンなどの芳香族炭化水素；ジエチルエーテル、ジメトキシエタン、テトラヒドロフラン、ジオキサンなどのエーテル；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドなどのアミド；ジメチルスルホキシド（ＤＭＳＯ）等を挙げることができる。これらの溶媒は単独で又は２種以上を混合して用いられる。 The reaction of the compound represented by the formula (4) and the compound represented by the formula (5) is performed in the presence or absence of a solvent. Examples of the solvent include aliphatic hydrocarbons such as hexane, heptane, and octane; alicyclic hydrocarbons such as cyclohexane; aromatic hydrocarbons such as benzene, toluene, xylene, and ethylbenzene; diethyl ether, dimethoxyethane, tetrahydrofuran, Examples include ethers such as dioxane; amides such as N, N-dimethylformamide and N, N-dimethylacetamide; dimethyl sulfoxide (DMSO) and the like. These solvents are used alone or in admixture of two or more.
上記式（４）で表される化合物と式（５）で表される化合物の反応の際の温度としては、例えば、０〜１００℃、好ましくは０〜５０℃程度である。反応時間は、例えば、０．５〜２４時間、好ましくは、０．５〜１８時間である。反応は常圧で行ってもよく、減圧又は加圧下で行ってもよい。反応の雰囲気は反応を阻害しない限り特に限定されず、例えば、窒素雰囲気、アルゴン雰囲気などの何れであってもよい。また、反応はバッチ式、セミバッチ式、連続式などの何れの方法で行うこともできる。 As temperature in the case of reaction of the compound represented by the said Formula (4), and the compound represented by Formula (5), it is 0-100 degreeC, for example, Preferably it is about 0-50 degreeC. The reaction time is, for example, 0.5 to 24 hours, preferably 0.5 to 18 hours. The reaction may be carried out at normal pressure or under reduced pressure or increased pressure. The reaction atmosphere is not particularly limited as long as the reaction is not inhibited, and may be any of nitrogen atmosphere, argon atmosphere, and the like. Further, the reaction can be carried out by any method such as batch, semi-batch and continuous methods.
反応終了後、反応生成物は、例えば、濾過、濃縮、蒸留、抽出、晶析、再結晶、カラムクロマトグラフィーなどの分離手段や、これらを組み合わせた分離手段により分離精製できる。 After completion of the reaction, the reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography, etc., or a separation means combining these.
上記式（３）中、Ｒ4は炭素数１〜６の脂肪族炭化水素基を示す。Ｘはハロゲン原子を示し、フッ素、塩素、臭素、ヨウ素の何れかである。 In the formula (3), R 4 is an aliphatic hydrocarbon group having 1 to 6 carbon atoms. X represents a halogen atom and is any one of fluorine, chlorine, bromine and iodine.
式（３）中のＲ4は、上記式（１）中のＡにおけるＲ4に対応する。 R 4 in the formula (3) corresponds to R 4 in A in the formula (1).
上記式（２）で表される化合物と、上記式（３）で表されるグリオキシル酸誘導体を酸触媒の存在下で反応させると、下記式（1a）で表される化合物［＝上記式（１）で表されるベンゾイルギ酸化合物において、ＡがＯＲ4である化合物］を得ることができる。下記式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は上記に同じ。 When the compound represented by the above formula (2) and the glyoxylic acid derivative represented by the above formula (3) are reacted in the presence of an acid catalyst, the compound represented by the following formula (1a) [= the above formula ( In the benzoylformic acid compound represented by 1), a compound in which A is OR 4 can be obtained. In the following formulae, R 1 , R 2 , R 3 and R 4 are the same as above.
酸触媒としては、従来のフリーデル・クラフツアシル化反応で用いられている酸触媒を使用することができ、なかでもルイス酸を使用することが好ましい。ルイス酸としては、例えば、三塩化アルミニウム、三臭化アルミニウム、三塩化ホウ素、三塩化鉄、二塩化亜鉛、四塩化スズ、四塩化チタン、三フッ化ホウ素等を挙げることができる。本発明においては、なかでも三塩化アルミニウムを使用することが好ましい。 As the acid catalyst, an acid catalyst used in a conventional Friedel-Crafts acylation reaction can be used, and among them, a Lewis acid is preferably used. Examples of the Lewis acid include aluminum trichloride, aluminum tribromide, boron trichloride, iron trichloride, zinc dichloride, tin tetrachloride, titanium tetrachloride, boron trifluoride and the like. In the present invention, it is particularly preferable to use aluminum trichloride.
酸触媒の使用量としては特に制限はなく、例えば、上記式（２）で表される化合物１モルに対して０．５〜２０モル程度（好ましくは、０．５〜５モル）である。 There is no restriction | limiting in particular as the usage-amount of an acid catalyst, For example, it is about 0.5-20 mol (preferably 0.5-5 mol) with respect to 1 mol of compounds represented by the said Formula (2).
また、上記式（３）で表されるグリオキシル酸誘導体の使用量としては、上記式（２）で表される化合物１モルに対して、例えば１〜３モル程度である。 Moreover, as the usage-amount of the glyoxylic acid derivative represented by the said Formula (3), it is about 1-3 mol with respect to 1 mol of compounds represented by the said Formula (2).
上記反応は、溶媒の存在下又は非存在下で行われる。前記溶媒としては、例えば、ヘキサン、ヘプタン、オクタンなどの脂肪族炭化水素；シクロヘキサンなどの脂環式炭化水素；ジエチルエーテル、ジメトキシエタン、テトラヒドロフラン、ジオキサンなどのエーテル；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドなどのアミド；ジメチルスルホキシド（ＤＭＳＯ）等を挙げることができる。これらの溶媒は単独で又は２種以上を混合して用いられる。 The above reaction is carried out in the presence or absence of a solvent. Examples of the solvent include aliphatic hydrocarbons such as hexane, heptane, and octane; alicyclic hydrocarbons such as cyclohexane; ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, and dioxane; N, N-dimethylformamide, N, Examples thereof include amides such as N-dimethylacetamide; dimethyl sulfoxide (DMSO) and the like. These solvents are used alone or in admixture of two or more.
上記反応における温度は、例えば、０〜１００℃、好ましくは０〜８０℃程度である。反応時間は、例えば、０．５〜１０時間、好ましくは、１〜８時間である。反応は常圧で行ってもよく、減圧又は加圧下で行ってもよい。反応の雰囲気は反応を阻害しない限り特に限定されず、例えば、窒素雰囲気、アルゴン雰囲気などの何れであってもよい。また、反応はバッチ式、セミバッチ式、連続式などの何れの方法で行うこともできる。 The temperature in the above reaction is, for example, about 0 to 100 ° C., preferably about 0 to 80 ° C. The reaction time is, for example, 0.5 to 10 hours, preferably 1 to 8 hours. The reaction may be carried out at normal pressure or under reduced pressure or increased pressure. The reaction atmosphere is not particularly limited as long as the reaction is not inhibited, and may be any of nitrogen atmosphere, argon atmosphere, and the like. Further, the reaction can be carried out by any method such as batch, semi-batch and continuous methods.
反応終了後、反応生成物は、例えば、濾過、濃縮、蒸留、抽出、晶析、再結晶、カラムクロマトグラフィーなどの分離手段や、これらを組み合わせた分離手段により分離精製できる。 After completion of the reaction, the reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography, etc., or a separation means combining these.
式（１）で表されるベンゾイルギ酸化合物におけるＡがヒドロキシル基である化合物［下記式（1b）で表されるベンゾイルギ酸化合物］は、上記式（1a）で表される化合物を、加水分解することにより合成することができる。下記式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は上記に同じ。 In the benzoylformic acid compound represented by formula (1), A is a hydroxyl group [benzoylformic acid compound represented by the following formula (1b)] hydrolyzes the compound represented by the above formula (1a). Can be synthesized. In the following formulae, R 1 , R 2 , R 3 and R 4 are the same as above.
上記加水分解反応は、例えば、水酸化ナトリウム等のアルカリ性条件下、又は塩酸等の酸性条件下で行うことができる。また、反応温度としては、例えば、０〜１００℃、好ましくは１０〜４０℃程度である。反応時間は、例えば、０．５〜３０時間程度である。 The hydrolysis reaction can be performed, for example, under alkaline conditions such as sodium hydroxide or acidic conditions such as hydrochloric acid. Moreover, as reaction temperature, it is 0-100 degreeC, for example, Preferably it is about 10-40 degreeC. The reaction time is, for example, about 0.5 to 30 hours.
上記加水分解反応は、溶媒の存在下又は非存在下で行われる。前記溶媒としては、上記式（２）で表される化合物と式（３）で表されるグリオキシル酸誘導体との反応の際に使用することができる溶媒と同様の例、及びメタノール、エタノール、イソプロピルアルコール、エチレングリコール等のアルコール類等を挙げることができる。上記式（２）で表される化合物と式（３）で表されるグリオキシル酸誘導体との反応を溶媒の存在下で行う場合、反応終了後、前記溶媒を留去して、得られた式（６）で表される化合物を新たな溶媒に再溶解して加水分解反応を行ってもよく、上記式（２）で表される化合物と式（３）で表されるグリオキシル酸誘導体との反応に使用した溶媒を留去することなく、続いて加水分解反応を行ってもよい。 The hydrolysis reaction is performed in the presence or absence of a solvent. Examples of the solvent include the same examples as the solvent that can be used in the reaction of the compound represented by the above formula (2) and the glyoxylic acid derivative represented by the formula (3), and methanol, ethanol, isopropyl Alcohols, such as alcohol and ethylene glycol, etc. can be mentioned. When the reaction between the compound represented by the above formula (2) and the glyoxylic acid derivative represented by the formula (3) is carried out in the presence of a solvent, the solvent is distilled off after completion of the reaction, and the obtained formula The compound represented by (6) may be redissolved in a new solvent to carry out a hydrolysis reaction. The compound represented by the above formula (2) and the glyoxylic acid derivative represented by the formula (3) Subsequently, the hydrolysis reaction may be carried out without distilling off the solvent used in the reaction.
更に、式（１）で表されるベンゾイルギ酸化合物におけるＡがハロゲン原子である化合物［下記式（1c）で表されるベンゾイルギ酸化合物］は、上記式（1b）で表されるベンゾイルギ酸化合物を、ハロゲン化剤を使用してハロゲン化することにより合成することができる。下記式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は上記に同じ。Ｘ”はハロゲン原子を示し、フッ素、塩素、臭素、ヨウ素の何れかである。 Furthermore, the compound [A benzoylformic acid compound represented by the following formula (1c)] in which A in the benzoylformic acid compound represented by the formula (1) is a halogen atom is a benzoylformic acid compound represented by the above formula (1b). It can be synthesized by halogenation using a halogenating agent. In the following formulae, R 1 , R 2 , R 3 and R 4 are the same as above. X ″ represents a halogen atom and is any one of fluorine, chlorine, bromine and iodine.
ハロゲン化剤としては、例えば、オキサリルハライド、ハロゲン化チオニル、ハロゲン化リン等を挙げることができる。本発明においては、なかでも、優れた選択率で上記式（1c）で表されるベンゾイルギ酸化合物を得ることができる点で、オキサリルハライドが好ましい。 Examples of the halogenating agent include oxalyl halide, thionyl halide, phosphorus halide and the like. In the present invention, among these, oxalyl halide is preferable in that the benzoylformic acid compound represented by the above formula (1c) can be obtained with excellent selectivity.
上記ハロゲン化反応は、溶媒の存在下又は非存在下で行われる。前記溶媒としては、上記式（２）で表される化合物と式（３）で表されるグリオキシル酸誘導体との反応の際に使用することができる溶媒と同様の例やベンゼン、トルエン、キシレン、エチルベンゼン、ｏ-ジクロロベンゼン等の芳香族炭化水素等を挙げることができる。また、Ｎ，Ｎ-ジメチルホルムアミド等を触媒として少量添加してもよい。 The halogenation reaction is performed in the presence or absence of a solvent. Examples of the solvent include the same examples as the solvent that can be used in the reaction of the compound represented by the formula (2) and the glyoxylic acid derivative represented by the formula (3), benzene, toluene, xylene, Aromatic hydrocarbons such as ethylbenzene and o-dichlorobenzene can be mentioned. A small amount of N, N-dimethylformamide or the like may be added as a catalyst.
上記ハロゲン化反応における反応温度は、例えば、０〜１００℃、好ましくは０〜８０℃程度である。反応時間は、例えば、０．５〜１０時間、好ましくは、１〜８時間である。反応は常圧で行ってもよく、減圧又は加圧下で行ってもよい。反応の雰囲気は反応を阻害しない限り特に限定されず、例えば、窒素雰囲気、アルゴン雰囲気などの何れであってもよい。また、反応はバッチ式、セミバッチ式、連続式などの何れの方法で行うこともできる。 The reaction temperature in the said halogenation reaction is 0-100 degreeC, for example, Preferably it is about 0-80 degreeC. The reaction time is, for example, 0.5 to 10 hours, preferably 1 to 8 hours. The reaction may be carried out at normal pressure or under reduced pressure or increased pressure. The reaction atmosphere is not particularly limited as long as the reaction is not inhibited, and may be any of nitrogen atmosphere, argon atmosphere, and the like. Further, the reaction can be carried out by any method such as batch, semi-batch and continuous methods.
反応終了後、反応生成物は、例えば、濾過、濃縮、蒸留、抽出、晶析、再結晶、カラムクロマトグラフィーなどの分離手段や、これらを組み合わせた分離手段により分離精製できる。 After completion of the reaction, the reaction product can be separated and purified by separation means such as filtration, concentration, distillation, extraction, crystallization, recrystallization, column chromatography, etc., or a separation means combining these.
本発明にかかるベンゾイルギ酸化合物の製造方法によれば、上記式（１）で表されるベンゾイルギ酸化合物を簡便、且つ効率よく合成することができる。また、前記方法により得られるベンゾイルギ酸化合物は、医薬、農薬、又はその中間体、電子材料中間体、光重合開始剤等として有用である。 According to the method for producing a benzoylformic acid compound according to the present invention, the benzoylformic acid compound represented by the above formula (1) can be synthesized easily and efficiently. In addition, the benzoylformic acid compound obtained by the above method is useful as a pharmaceutical, agricultural chemical, or an intermediate thereof, an electronic material intermediate, a photopolymerization initiator, and the like.
以下、実施例により本発明をより具体的に説明するが、本発明はこれらの実施例により限定されるものではない。尚、得られた化合物の純度及び収率の測定にはガスクロマトグラフィーを使用した。 EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited by these Examples. In addition, gas chromatography was used for the measurement of the purity and yield of the obtained compound.
実施例１
工程１［１−（２−エチルヘキシルチオ）−２，５−ジメチル−ベンゼンの合成］
２，５−ジメチルベンゼンチオール １５０．０ｇ（１．０９ｍｏｌ）と炭酸カリウム ３００．０ｇ（２．１７ｍｏｌ）をＮ，Ｎ−ジメチルホルムアミド ７５０ｇと混合し、５〜１０℃に冷却した。
そこへ、２−エチルヘキシルブロミド ２０９．６ｇ（１．０９ｍｏｌ）を内温１０±５℃の範囲で滴下した。滴下終了後、温度を２０〜２５℃に保持して１時間反応した。
反応液中の２，５−ジメチルベンゼンチオールの消失が確認できたため、シクロヘキサン ７５０ｇと水 ６００ｇを添加し、生成物を抽出した。分液した有機層に水 ６００ｇを加え、水層のｐＨが６〜７になるように塩酸を添加し、洗浄した。さらに分液した有機層を水 ６００ｇで洗浄し、エバポレーターにてシクロヘキサンを留去することで、下記式で表される１−（２−エチルヘキシルチオ）−２，５−ジメチル−ベンゼンを２６９．６ｇ取得した（純度：９７重量％、収率：９６％）。
Example 1
Step 1 [Synthesis of 1- (2-ethylhexylthio) -2,5-dimethyl-benzene]
150.0 g (1.09 mol) of 2,5-dimethylbenzenethiol and 300.0 g (2.17 mol) of potassium carbonate were mixed with 750 g of N, N-dimethylformamide and cooled to 5 to 10 ° C.
Thereto, 209.6 g (1.09 mol) of 2-ethylhexyl bromide was dropped in an internal temperature range of 10 ± 5 ° C. After completion of the dropwise addition, the temperature was kept at 20 to 25 ° C. and reacted for 1 hour.
Since the disappearance of 2,5-dimethylbenzenethiol in the reaction solution was confirmed, 750 g of cyclohexane and 600 g of water were added, and the product was extracted. 600 g of water was added to the separated organic layer, and hydrochloric acid was added and washed so that the pH of the aqueous layer was 6-7. Further, the separated organic layer was washed with 600 g of water, and cyclohexane was distilled off with an evaporator, thereby obtaining 269.6 g of 1- (2-ethylhexylthio) -2,5-dimethyl-benzene represented by the following formula. Obtained (purity: 97% by weight, yield: 96%).
工程２［４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸エチルの合成］
塩化アルミニウム ２．９ｇ（０．０２２ｍｏｌ）、シクロヘキサン １０．０ｇを混合し、１０〜１５℃に冷却した。
そこへ上記工程１で得られた１−（２−エチルヘキシルチオ）−２，５−ジメチルベンゼン（純度：９７重量％）５．０ｇ（０．０２０ｍｏｌ）をゆっくり滴下しながら内温を０〜５℃に調整した。
次に、クロログリオキシル酸エチル ３．０ｇ（０．０２２ｍｏｌ）を内温０〜１０℃で滴下した。滴下途中にシクロヘキサン ３．５ｇを添加した。滴下終了後、内温を２５〜２８℃に保持して２時間反応し、さらに内温を４０℃に昇温して１．５時間反応した。その後、室温に冷却し、エチルメチルケトン １０ｇを滴下した。
次に、その溶液を希塩酸（０．４重量％）２５．７ｇに滴下した。有機層を水 ２５．０ｇで２回洗浄し、エチルメチルケトン、シクロヘキサンを留去して、４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸エチルを５．３７ｇ取得した（純度：６５重量％、収率：５０％）。
シリカゲルカラムクロマトグラフィー（展開溶媒として、ｎ−ヘキサン：酢酸エチル＝４：１(v/v)を使用）を使用して精製し、純度９９重量％の４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸エチルを得た。
1H-NMR（500MHz,CDCl3） δ0.90〜0.95 (6H, m), δ1.31〜1.33 (4H, m), δ1.42 (3H, t), δ1.44〜1.57(4H, m), δ1.66〜1.71 (1H, m), δ2.30 (3H, s), δ2.59 (3H, s), δ2.95 (2H, d), δ4.4 (2H, q), δ7.03 (1H, s), δ7.41 (1H, s)
13C-NMR(500MHz,CDCl3） δ10.8, δ14.0, δ14.1, δ19.5, δ21.5, δ22.9, δ25.8, δ28.8, δ32.6, δ35.7, δ38.5, δ62.0, δ126.5, δ127.3, δ132.7, δ133.3, δ139.5, δ146.6, δ165.1, δ188.0
Step 2 [Synthesis of ethyl 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate]
2.9 g (0.022 mol) of aluminum chloride and 10.0 g of cyclohexane were mixed and cooled to 10 to 15 ° C.
While slowly dropping 5.0 g (0.020 mol) of 1- (2-ethylhexylthio) -2,5-dimethylbenzene (purity: 97 wt%) obtained in Step 1 above, the internal temperature was adjusted to 0-5. Adjusted to ° C.
Next, 3.0 g (0.022 mol) of ethyl chloroglyoxylate was added dropwise at an internal temperature of 0 to 10 ° C. In the middle of dropping, 3.5 g of cyclohexane was added. After completion of the dropwise addition, the reaction was continued for 2 hours while maintaining the internal temperature at 25-28 ° C, and the reaction was continued for 1.5 hours by raising the internal temperature to 40 ° C. Then, it cooled to room temperature and ethyl methyl ketone 10g was dripped.
Next, the solution was added dropwise to 25.7 g of diluted hydrochloric acid (0.4 wt%). The organic layer was washed twice with 25.0 g of water, and ethyl methyl ketone and cyclohexane were distilled off to obtain 5.37 g of ethyl 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate (purity: 65 wt%, yield: 50%).
Purification was performed using silica gel column chromatography (using n-hexane: ethyl acetate = 4: 1 (v / v) as a developing solvent), and 4- (2-ethylhexylthio) -2, having a purity of 99% by weight, Ethyl 5-dimethylbenzoylformate was obtained.
1 H-NMR (500 MHz, CDCl 3 ) δ0.90 to 0.95 (6H, m), δ1.31 to 1.33 (4H, m), δ1.42 (3H, t), δ1.44 to 1.57 (4H, m ), δ1.66 to 1.71 (1H, m), δ2.30 (3H, s), δ2.59 (3H, s), δ2.95 (2H, d), δ4.4 (2H, q), δ7 .03 (1H, s), δ7.41 (1H, s)
13 C-NMR (500 MHz, CDCl 3 ) δ10.8, δ14.0, δ14.1, δ19.5, δ21.5, δ22.9, δ25.8, δ28.8, δ32.6, δ35.7, δ38.5, δ62.0, δ126.5, δ127.3, δ132.7, δ133.3, δ139.5, δ146.6, δ165.1, δ188.0
工程３［４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸の合成］
上記工程２で得られた４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸エチル（純度：６５重量％）４．６ｇ（０．００８６ｍｏｌ）に、室温下、５重量％水酸化ナトリウム水溶液 １３．７ｇ（０．０１７ｍｏｌ）、メタノール ３．４ｇを添加し、内温２３〜２７℃で１．５時間反応した。
４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸エチルの消失を確認後、トルエン １５ｇを添加した。さらにエチレングリコール ５．０ｇを添加し、トルエン層と水層の界面を確認してトルエン層を除去した。
分液した水層に３５重量％塩酸 １．３ｇを滴下しｐＨを２〜３に調整し、酢酸エチル １５ｇで抽出した。分液した酢酸エチル層を水 １５ｇで２回洗浄し、エバポレーターで酢酸エチルを留去して、４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸のＣｒｕｄｅ品 ３．０ｇ得た（純度：５８重量％、収率：６３％）。
４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸のＣｒｕｄｅ品をシリカゲルカラムクロマトグラフィー（展開溶媒として、ｎ−ヘキサン：酢酸エチル＝２：１(v/v)を使用）を使用して精製し、純度９８重量％の４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸を１．５ｇ取得した。
1H-NMR（500MHz,CDCl3） δ0.90〜0.96 (6H, m), δ1.31〜1.34 (4H, m), δ1.44〜1.57(4H, m), δ1.67〜1.72 (1H, m), δ2.32 (3H, s), δ2.59 (3H, s), δ2.97 (2H, d), δ7.05 (1H, s), δ7.82 (1H, s), δ10.0 (1H, s)
13C-NMR（500MHz,CDCl3） δ10.8, δ14.0, δ19.5, δ21.7, δ22.9, δ25.8, δ28.8, δ32.6, δ35.6, δ38.5, δ125.7, δ127.1, δ132.8, δ133.9, δ140.2, δ147.7, δ165.1, δ185.9
Step 3 [Synthesis of 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformic acid]
To 4.6 g (0.0086 mol) of ethyl 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate (purity: 65% by weight) obtained in Step 2 above, 5% by weight sodium hydroxide at room temperature 13.7 g (0.017 mol) of an aqueous solution and 3.4 g of methanol were added and reacted at an internal temperature of 23 to 27 ° C. for 1.5 hours.
After confirming the disappearance of ethyl 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate, 15 g of toluene was added. Further, 5.0 g of ethylene glycol was added, the interface between the toluene layer and the aqueous layer was confirmed, and the toluene layer was removed.
To the separated aqueous layer, 1.3 g of 35% by weight hydrochloric acid was added dropwise to adjust the pH to 2 to 3, followed by extraction with 15 g of ethyl acetate. The separated ethyl acetate layer was washed twice with 15 g of water, and the ethyl acetate was distilled off with an evaporator to obtain 3.0 g of a crude product of 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate ( (Purity: 58% by weight, yield: 63%).
Using a Crude product of 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate using silica gel column chromatography (using n-hexane: ethyl acetate = 2: 1 (v / v) as a developing solvent). And 1.5 g of 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformic acid having a purity of 98% by weight was obtained.
1 H-NMR (500 MHz, CDCl 3 ) δ0.90 to 0.96 (6H, m), δ1.31 to 1.34 (4H, m), δ1.44 to 1.57 (4H, m), δ1.67 to 1.72 (1H , m), δ2.32 (3H, s), δ2.59 (3H, s), δ2.97 (2H, d), δ7.05 (1H, s), δ7.82 (1H, s), δ10 .0 (1H, s)
13 C-NMR (500 MHz, CDCl 3 ) δ10.8, δ14.0, δ19.5, δ21.7, δ22.9, δ25.8, δ28.8, δ32.6, δ35.6, δ38.5, δ125.7, δ127.1, δ132.8, δ133.9, δ140.2, δ147.7, δ165.1, δ185.9
工程４［４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸クロリドの合成］
上記工程３で得られた４‐(２‐エチルヘキシルチオ)‐２，５-ジメチルベンゾイルギ酸 ２．３９ｇ(純度８５％、０．００６３ｍｏｌ)にＮ，Ｎ-ジメチルホルムアミド ０．０１２３ｇ(０．０００２ｍｏｌ)とｏ-ジクロロベンゼン ６．０ｇを加え、内温１５〜２０℃の範囲でオキサリルクロリド ０．９ｇ(０．００７ｍｏｌ)を滴下し、３時間反応して、４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸クロリドを得た（反応液の一部をエタノールと混合したところ、４-(２-エチルヘキシルチオ)-２，５-ジメチルベンゾイルギ酸エチルの生成が認められたため、４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸クロリドが生成していることを確認できた）。
Step 4 [Synthesis of 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate chloride]
4- (2-Ethylhexylthio) -2,5-dimethylbenzoylformic acid obtained in Step 3 above (2.39 g, purity 85%, 0.0063 mol) and N, N-dimethylformamide (0.0123 g, 0.0002 mol) And 6.0 g of o-dichlorobenzene were added, 0.9 g (0.007 mol) of oxalyl chloride was added dropwise within the range of 15 to 20 ° C., and reacted for 3 hours to give 4- (2-ethylhexylthio) -2. , 5-Dimethylbenzoylformate chloride was obtained (a portion of the reaction mixture was mixed with ethanol, and formation of ethyl 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate was observed. 2-ethylhexylthio) -2,5-dimethylbenzoyl formic acid chloride was confirmed to be formed).
実施例２
塩化アルミニウム ２．９ｇ（０．０２２ｍｏｌ）、シクロヘキサン １０．０ｇを混合し、１０〜１５℃に冷却し、クロログリオキシル酸エチル ８．９９ｇ（０．０６６ｍｏｌ）を内温０〜１０℃で滴下し撹拌した。
そこへ、上記実施例１の工程１で得られた１−（２−エチルヘキシルチオ）−２，５−ジメチルベンゼン １５．０ｇ（０．０６ｍｏｌ）とシクロヘキサン １５．０ｇを混合した溶液を内温０〜１０℃でゆっくり滴下した。滴下終了後、内温を０〜１０℃に保持して１．５時間反応し、さらに内温を４０℃に昇温して１．５時間反応した。その後、室温に冷却し、エチルメチルケトン ３０．０ｇを滴下した。
次に、その溶液を希塩酸（０．４重量％）７７．１ｇに滴下した。有機層を水７５．０ｇで２回洗浄し、４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸エチル／シクロヘキサン溶液を６９．４ｇ（濃度１２．６重量％）得た。
Example 2
2.9 g (0.022 mol) of aluminum chloride and 10.0 g of cyclohexane were mixed and cooled to 10 to 15 ° C., and 8.99 g (0.066 mol) of ethyl chloroglyoxylate was added dropwise at an internal temperature of 0 to 10 ° C. and stirred. did.
A solution prepared by mixing 15.0 g (0.06 mol) of 1- (2-ethylhexylthio) -2,5-dimethylbenzene and 15.0 g of cyclohexane obtained in Step 1 of Example 1 was used. Slowly dropwise at -10 ° C. After completion of the dropping, the reaction was carried out for 1.5 hours while maintaining the internal temperature at 0 to 10 ° C., and the reaction was carried out for 1.5 hours by raising the internal temperature to 40 ° C. Then, it cooled to room temperature and 30.0 g of ethyl methyl ketone was dripped.
Next, the solution was added dropwise to 77.1 g of dilute hydrochloric acid (0.4 wt%). The organic layer was washed twice with 75.0 g of water to obtain 69.4 g (concentration 12.6% by weight) of ethyl 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate / cyclohexane.
得られた４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸エチル／シクロヘキサン溶液に５重量％水酸化ナトリウム水溶液 １９．９ｇとエチレングリコール １７．４ｇを添加し、内温２０〜３０℃で反応した。原料の残存があったため、５重量％水酸化ナトリウム水溶液１９．９ｇを追加し反応を継続した。４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸エチルの消失を確認後、シクロヘキサン層を除去した。分液した水層にシクロヘキサン ４０ｇを加えて洗浄した。シクロヘキサンとエチレングリコールを添加して、界面が確認できたところで分液し、シクロヘキサン層を除去した。分液した水層に３５重量％塩酸 ５．２ｇを滴下し、トルエン ６１ｇで抽出した。
トルエン層を食塩水 １００ｇで２回洗浄し、トルエンを留去して４−（２−エチルヘキシルチオ）−２，５−ジメチルベンゾイルギ酸を１２．２ｇ（純度：７４重量％、一貫収率：４７％）得た。
To the obtained ethyl 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate / cyclohexane solution, 19.9 g of 5 wt% aqueous sodium hydroxide solution and 17.4 g of ethylene glycol were added, and the internal temperature was 20-30 ° C. It reacted with. Since the raw material remained, 19.9 g of 5 wt% aqueous sodium hydroxide solution was added and the reaction was continued. After confirming the disappearance of ethyl 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformate, the cyclohexane layer was removed. The separated aqueous layer was washed with 40 g of cyclohexane. Cyclohexane and ethylene glycol were added, liquid separation was performed when the interface was confirmed, and the cyclohexane layer was removed. To the separated aqueous layer, 5.2 g of 35% by weight hydrochloric acid was added dropwise and extracted with 61 g of toluene.
The toluene layer was washed twice with 100 g of brine, and toluene was distilled off to give 12.2 g of 4- (2-ethylhexylthio) -2,5-dimethylbenzoylformic acid (purity: 74% by weight, consistent yield: 47 %)Obtained.
Claims (3)
で表されるベンゾイルギ酸化合物。 Following formula (1)
A benzoylformic acid compound represented by:
で表される化合物と、下記式（３）
で表されるグリオキシル酸誘導体を、酸触媒の存在下で反応させる工程を経て、下記式（１）
で表されるベンゾイルギ酸化合物を得るベンゾイルギ酸化合物の製造方法。 Following formula (2)
And a compound represented by the following formula (3)
Through the step of reacting the glyoxylic acid derivative represented by the following formula (1):
The manufacturing method of the benzoyl formate compound which obtains the benzoyl formate compound represented by these.
で表される化合物。 Following formula (2)
A compound represented by
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| JP7025531B2 (en) | 2017-09-06 | 2022-02-24 | 常州強力電子新材料股▲分▼有限公司 | Sulfonium salt photoinitiator, its production method, photocurable composition containing it and its application |
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