JP2004180505A - Method for producing unsaturated carboxylic acid ester - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a bulky unsaturated carboxylic acid ester for resists, or the like, under mild conditions without using an acidic catalyst. <P>SOLUTION: The method for producing the unsaturated carboxylic acid ester represented by formula (3) (wherein, X<SP>1</SP>denotes C(O), O-C(O), C(O)-O or CO-O-C(O); (a) and (b) denote each an integer of 0-2; Z denotes a cyclic saturated hydrocarbon group which may have a substituent; and R<SP>2</SP>denotes hydrogen atom or a 1-4C alkyl group which may have a substituent) or formula (3) having a substituent is carried out as follows. A specific bulky alcohol or ester is reacted with the specific unsaturated carboxylic acid or the specific unsaturated carboxylic acid ester in the presence of the catalyst having an ability to catalyze an esterification or a transesterification. Thereby, the esterification or transesterification is carried out. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

（式中、Ｒ^１は水素または炭素数１〜６のアシル基、Ｘ^１は−Ｃ（Ｏ）−、−Ｏ−Ｃ（Ｏ）−、−Ｃ（Ｏ）−Ｏ−または−Ｃ（Ｏ）−Ｏ−Ｃ（Ｏ）−を表し、ａ、ｂはそれぞれ０〜２の整数を表し、Ｚは置換基を有していてもよい環式飽和炭化水素基を表す。Ｚの環状骨格中のメチレン基は酸素原子または硫黄原子で置き換えられていてもよい。）
【００１５】
【化９】

（Ｒ^２は水素原子または置換基を有していてもよい炭素数１〜４のアルキル基を表し、Ｒ^３は水素原子または置換基を表す。）
【００１６】
【化１０】

（式中、Ｚ、Ｘ^１、ａ、ｂは前記式（１）と同義であり、Ｒ^２は前記式（２）と同義である。）
【００１７】
【発明の実施の形態】
本発明において、前記式（３）または置換基を有する式（３）で表される不飽和カルボン酸エステル（以下、これらをまとめて式（３）で表される不飽和カルボン酸エステルとも言う。）は、エステル化またはエステル交換反応を触媒する能力を有する生体由来の触媒の存在下、前記式（１）または置換基を有する式（１）で表される化合物（以下、これらをまとめて式（１）で表される化合物とも言う。）と前記式（２）で表される化合物から製造する。
【００１８】
式（１）において、Ｘ^１を含む環構造は、Ｘ^１が−Ｃ（Ｏ）−の場合は環状ケトン、−Ｏ−Ｃ（Ｏ）−または−Ｃ（Ｏ）−Ｏ−の場合はラクトン、−Ｃ（Ｏ）−Ｏ−Ｃ（Ｏ）−の場合は酸無水物である。反応時または精製時の副反応が少ないことから、Ｘ^１は−Ｃ（Ｏ）−、−Ｏ−Ｃ（Ｏ）−または−Ｃ（Ｏ）−Ｏ−が好ましい。また、反応性の点から、Ｘ^１は−Ｏ−Ｃ（Ｏ）−または−Ｃ（Ｏ）−Ｏ−が好ましい。
【００１９】
式（１）において、Ｒ^１は水素または炭素数１〜６のアシル基である。炭素数１〜６のアシル基としては、例えば、ホルミル基、アセチル基、プロピオニル基、ブチリル基、イソブチリル基、バレリル基、イソバレリル基等が挙げられる。反応性の点から、Ｒ^１としては水素原子、ホルミル基、アセチル基が好ましい。
【００２０】
式（１）において、Ｒ^１Ｏで表される基は複数でもよい。Ｒ^１Ｏで表される基が複数の場合、使用する生体触媒の種類や数によっては、特定のＲ^１Ｏで表される基だけをエステル化またはエステル交換したり、全てのＲ^１Ｏで表される基をエステル化またはエステル交換したりできる。
【００２１】
式（１）において、ａ、ｂはそれぞれ０〜２の整数である。ａ、ｂはそれぞれ０または１が好ましい。反応時または精製時の原料および生成物の安定性の点から、ａ＋ｂは、Ｘ^１が−Ｃ（Ｏ）−の場合は１〜２が好ましく、−Ｏ−Ｃ（Ｏ）−または−Ｃ（Ｏ）−Ｏ−の場合は０〜２が好ましく、−Ｃ（Ｏ）−Ｏ−Ｃ（Ｏ）−の場合は０〜１が好ましい。
【００２２】
式（１）において、Ｚは置換基を有していてもよい環式飽和炭化水素基であり、単環式飽和炭化水素基または多環式飽和炭化水素基のいずれでもよい。多環式飽和炭化水素基としては、例えば、縮合多環式飽和炭化水素基、橋かけ環式飽和炭化水素基、スピロ飽和炭化水素基およびこれらの基を含む基が挙げられる。本発明の方法で得られる式（３）で表される化合物のレジスト用構成成分樹脂等の原料として求められる重合体の熱安定性、ドライエッチング耐性等の点から、Ｚは多環式飽和炭化水素基が好ましく、橋かけ環式飽和炭化水素基がより好ましい。
【００２３】
置換基（以下、第１置換基と言う。）を有する式（１）で表される化合物における第１置換基としては、例えば、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、ｓｅｃ−ブチル基、ｔｅｒｔ−ブチル基、ｔｅｒｔ−アミル基、ｎ−ペンチル基、ｎ−ヘキシル基等の炭素数１〜６のアルキル基；ビニル基、プロペニル基、ブテニル基等の炭素数２〜４のアルケニル基；エチニル基、プロピニル基、ブチニル基、ペンチニル基、ヘキシニル基等の炭素数２〜６のアルキニル基；メトキシ基、エトキシ基、プロポキシ基、ブトキシ基等の炭素数１〜４のアルコキシ基；メチルチオ基、エチルチオ基、プロピルチオ基、ブチルチオ基等の炭素数１〜４のアルキルチオ基；ホルムアミド基、アセトアミド基、プロピオンアミド基、ヘキサンアミド基等の炭素数１〜７のアミド基；シアノ基；ホルミル基、アセチル基、プロピオニル基、ブチリル基等の炭素数１〜４のアシル基；メトキシカルボニル基、エトキシカルボニル基、プロポキシカルボニル基等の炭素数２〜４のアルコキシカルボニル基；ベンジル基、フェネチル基、ナフチルメチル基等のアラルキル基；メチルアミノ基、ジメチルアミノ基、エチルアミノ基、プロピルアミノ基、ブチルアミノ基等の炭素数１〜４のアルキル基を有しているアミノ基；ニトロ基；およびチオール基等の置換基やそれらから誘導化された置換基等が挙げられる。前記のアルキル基、アルケニル基、アルキニル基、アルコキシ基、アルキルチオ基、アミド基、アシル基、アルコキシカルボニル基、アラルキル基、アルキル基を有しているアミノ基等の置換基は、ハロゲン等の第２置換基を有していてもよい。第２置換基としては、炭素数１〜６のアルキル基が好ましく、メチル基、エチル基がより好ましい。
【００２４】
また、Ｚの環状骨格を構成するメチレン基は、酸素原子または硫黄原子に置き換えられていてもよい。Ｒ^１Ｏ−Ｚの具体例としては次の式（８）〜（２５）が挙げられる。
【００２５】
【化１１】

（式中、Ｒ^１は式（１）と同義である。）
【００２６】
また、式（１）で表される化合物の付加反応に対する反応性の点から、Ｒ^１Ｏ−Ｚとしては式（４）で表される環式飽和炭化水素基が好ましい。
【００２７】
【化１２】

（式中、Ｒ^１は式（１）と同義であり、Ｒ^４〜Ｒ^９は、独立している場合、水素原子、炭素数１〜６の直鎖若しくは分岐アルキル基を表す。また、Ｒ^４〜Ｒ^９は一緒になって炭素数１〜６のメチレン鎖であってもよい。メチレン鎖の水素は炭素数１〜２のアルキル基で置換されていてもよく、またメチレン鎖の途中に−Ｏ−、−Ｓ−を有していてもよい。さらに、Ｒ^４とＲ^５は一緒になって−Ｏ−または−Ｓ−であってもよい。）
【００２８】
式（４）における炭素数１〜６の直鎖若しくは分岐アルキル基としては、例えば、メチル基、エチル基、プロピル基、イソプロピル基、ｎ−ブチル基、ｓｅｃ−ブチル基、ｔｅｒｔ−ブチル基、ｔｅｒｔ−アミル基、ｎ−ペンチル基、ｎ−ヘキシル基等が挙げられる。
【００２９】
また、式（４）における途中に−Ｏ−、−Ｓ−を有する炭素数１〜６のメチレン鎖としては、例えば、−ＣＨ_２−Ｏ−ＣＨ_２−、−ＣＨ_２−Ｏ−（ＣＨ_２）_２−、−ＣＨ_２−Ｏ−（ＣＨ_２）_３−、−ＣＨ_２−Ｏ−（ＣＨ_２）_４−、−ＣＨ_２−Ｏ−（ＣＨ_２）_５−、−（ＣＨ_２）_２−Ｏ−（ＣＨ_２）_２−、−（ＣＨ_２）_２−Ｏ−（ＣＨ_２）_３−、−（ＣＨ_２）_２−Ｏ−（ＣＨ_２）_４−、−（ＣＨ_２）_３−Ｏ−（ＣＨ_２）_３−、−ＣＨ_２−Ｓ−ＣＨ_２−、−ＣＨ_２−Ｓ−（ＣＨ_２）_２−、−ＣＨ_２−Ｓ−（ＣＨ_２）_３−、−ＣＨ_２−Ｓ−（ＣＨ_２）_４−、−ＣＨ_２−Ｓ−（ＣＨ_２）_５−、−（ＣＨ_２）_２−Ｓ−（ＣＨ_２）_２−、−（ＣＨ_２）_２−Ｓ−（ＣＨ_２）_３−、−（ＣＨ_２）_２−Ｓ−（ＣＨ_２）_４−、−（ＣＨ_２）_３−Ｓ−（ＣＨ_２）_３−等が挙げられる。
【００３０】
式（４）で表される環式飽和炭化水素基の具体例としては次の式（２６）〜（４３）が挙げられる。
【００３１】
【化１３】

【００３２】
さらに、式（１）で表される化合物としては、式（６）または炭素数１〜６の直鎖若しくは分岐アルキル基を置換基として有する式（６）で表される化合物（以下、これらをまとめて式（６）で表される化合物とも言う。）がより好ましい。
【００３３】
【化１４】

（式中、Ｒ^１は式（１）と同義であり、Ｘ^２は−Ｏ−Ｃ（Ｏ）−または−Ｃ（Ｏ）−Ｏ−を表し、ｃ、ｄはそれぞれ０または１の整数を表し、Ｗは−ＣＨ_２−または−Ｏ−を表す。）
【００３４】
式（６）で表される化合物としては、次の式（４４）〜（４９）の化合物、および炭素数１〜６の直鎖若しくは分岐アルキル基を有する式（４４）〜（４９）の化合物が挙げられる。反応性、目的物選択性の観点から、式（４４）〜（４６）で表される化合物、およびその幾何異性体、光学異性体または鏡像異性体等の異性体が特に好ましい。
【００３５】
【化１５】

【００３６】
式（１）で表される化合物は、Ｊ．Ｃｈｅｍ．Ｓｏｃ．，Ｐｅｒｋｉｎ Ｔｒａｎｓ．１（１９９６），２３０９−２３１３、Ｊ．Ｃｈｅｍ．Ｓｏｃ．， （１９５９），２２１−２２６、特開２００１−１８８３５１号公報、ＷＯ０２／４６１７９号公報、特開２０００−１５９７５８号公報等に記載の製法によって製造可能である。
【００３７】
以上の化合物と、エステル化またはエステル交換反応させるのに使用する式（２）で表される化合物において、Ｒ^２は水素原子またはメチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、ｔ−ブチル基であり、このアルキル基は、ハロゲン等の置換基を有していてもよい。Ｒ^２は、好ましくは、水素原子またはメチル基である。また、Ｒ^３は水素原子または置換基であり、この置換基としては、例えば、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、ペンチル基、ヘキシル基等の炭素数１〜６のアルキル基；ビニル基、プロペニル基、ブテニル基、ペンテニル基、ヘキセニル基等の炭素数２〜６のアルケニル基；エチニル基、プロピニル基、ブチニル基、ペンチニル基、ヘキシニル基等の炭素数２〜６のアルキニル基；およびベンジル基、フェネチル基、ナフチルメチル基等のアラルキル基等が挙げられる。前記のアルキル基、アルケニル基、アルキニル基、アラルキル基等の置換基は、炭素数１〜４のアルコキシ基、炭素数１〜４のアルキルチオ基、炭素数１〜４のアミド基、炭素数１〜４のアシル基、シアノ基等の置換基を有していてもよい。Ｒ^３は、好ましくは、水素原子、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、ビニル基、１−メトキシビニル基、１−エトキシビニル基である。
【００３８】
式（１）で表される化合物と式（２）で表される化合物とを生体触媒の存在下で反応させて、エステル化またはエステル交換反応を行うことにより、式（３）で表される不飽和カルボン酸エステルを製造することができる。
【００３９】
また、Ｒ^１Ｏ−Ｚが式（４）である式（１）で表される化合物と式（２）で表される化合物とを生体触媒の存在下で反応させて、エステル化またはエステル交換反応を行うことにより、式（５）で表される不飽和カルボン酸エステルを製造することができる。
【００４０】
【化１６】

（式中、Ｘ^１は式（１）と同義であり、Ｒ^２は式（２）と同義であり、Ｒ^４〜Ｒ^９は式（４）と同義である。）
【００４１】
さらに式（６）で表される化合物と式（２）で表される化合物とを生体触媒の存在下で反応させて、エステル化またはエステル交換反応を行うことにより、式（７）で表される不飽和カルボン酸エステルを製造することができる。
【００４２】
【化１７】

（式中、Ｒ^２は式（２）と同義であり、Ｘ^２、Ｗ、ｃ、ｄは式（６）と同義である。）
【００４３】
本発明において使用する生体触媒は、前記エステル化またはエステル交換反応を触媒する能力を有する生体由来のものであれば、その種類および起源は特に限定されないが、中でも、微生物または動植物由来の酵素が好ましく、その中でもリパーゼ活性、エステラーゼ活性、プロテアーゼ活性およびアミダーゼ活性等の加水分解活性を有する酵素が特に好ましい。
【００４４】
微生物由来の酵素としては、例えば、天野エンザイム社リパーゼＰ（Ｐｓｅｕｄｏｍｏｎａｓ属由来）、天野エンザイム社リパーゼＰＳ（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ由来）、天野エンザイム社リパーゼＡ６（Ａｓｐｅｒｇｉｌｌｕｓ属由来）、天野エンザイム社リパーゼＡＰ６（Ａｓｐｅｒｇｉｌｌｕｓ属由来）、天野エンザイム社リパーゼＭ−１０（Ｍｕｃｏｒ属由来）、名糖産業社リパーゼＯＦ（Ｃａｎｄｉｄａ属由来）、名糖産業社リパーゼＰＬ（Ａｌｃａｌｉｇｅｎｅｓ属由来）、名糖産業社リパーゼＱＬＭ（Ａｌｃａｌｉｇｅｎｅｓ属由来）、名糖産業社リパーゼＳＬ（Ｂｕｒｋｈｏｌｄｅｒｉａ属由来）、名糖産業社リパーゼＴＬ（Ｐｓｅｕｄｏｍｏｎａｓ属由来）、名糖産業社リパーゼＭＹ（Ｃａｎｄｉｄａ属由来）、東洋紡社トヨチームＬＩＰ（Ｐｓｅｕｄｏｍｏｎａｓ属由来）、ＳＩＧＭＡ社Ｌｉｐａｓｅ Ｔｙｐｅ ＶＩＩ（Ｃａｎｄｉｄａ ｒｕｇｏｓａ由来）、ＳＩＧＭＡ社Ａｃｙｌａｓｅ Ｉ（Ａｓｐｅｒｇｉｌｌｕｓ ｍｅｌｌｅｕｓ由来）、ＳＩＧＭＡ社Ｐｒｏｔｅａｓｅ Ｔｙｐｅ ＸＸＸＩ（Ｂａｃｉｌｌｕｓ ｌｉｃｈｅｎｉｆｏｒｍｉｓ由来）、Ｆｌｕｋａ社Ｌｉｐａｓｅ（Ｃａｎｄｉｄａ ａｎｔａｒｃｔｉｃａ由来）、ＮＯＶＯ社Ｌｉｐｏｚｙｍｅ ＩＭ ２０（Ｈｕｍｉｃｏｌａ ｌａｎｕｇｉｎｏｓａ由来）、天野エンザイム社リパーゼＭ（Ｍｕｃｏｒ ｊａｖａｎｉｃｕｓ由来）、天野エンザイム社リパーゼＭＦＬ、ＮＯＶＯ社Ｎｏｖｏｚｙｍ４３５（Ｃａｎｄｉｄａ ａｎｔａｒｃｔｉｃａ由来）、ＮＯＶＯ社Ｌｉｐｏｚｙｍｅ ＲＭ ＩＭ（Ｒｈｉｚｏｍｕｃｏｒ ｍｉｅｈｅｉ由来）、ＮＯＶＯ社ＬｉｐｏｚｙｍｅＴＬ ＩＭ（Ｔｈｅｒｍｏｍｙｃｅｓ ｌａｎｕｇｉｎｏｓｕｓ由来）、ＮＯＶＯ社Ａｌｃａｌａｓｅ（Ｂａｃｉｌｌｕｓ ｌｉｃｈｅｎｉｆｏｒｍｉｓ由来）、ＮＯＶＯ社Ｄｕｒａｚｙｍ（Ｂａｃｉｌｌｕｓ属由来）、ＮＯＶＯ社Ｅｓｐｅｒａｓｅ（Ｂａｃｉｌｌｕｓ属由来）、ＮＯＶＯ社Ｓａｖｉｎａｓｅ（Ｂａｃｉｌｌｕｓ属由来）、ナガセ生化学工業社ビオプラーゼコンク（Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ由来）、天野エンザイム社リパーゼ ＡＹ（Ｃａｎｄｉｄａ ｒｕｇｏｓａ由来）、ナガセ生化学工業社リリパーゼＡ−１０（Ｒｈｉｚｏｐｕｓ ｊａｐｏｎｉｃｕｓ由来）、ナガセ生化学工業社リパーゼ２Ｇ（Ｐｓｅｕｄｏｍｏｎａｓ属由来）、ナガセ生化学工業社ビオプラーゼ ＡＬ−１５ＦＧ（Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ由来）、天野エンザイム社リパーゼＰＳ−Ｃ ”Ａｍａｎｏ” Ｉ（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ由来）、天野エンザイム社リパーゼＰＳ−Ｃ ”Ａｍａｎｏ” ＩＩ（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ由来）、天野エンザイム社リパーゼＰＳ−Ｄ ”Ａｍａｎｏ” Ｉ（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ由来）、天野エンザイム社リパーゼＡＫ ”Ａｍａｎｏ”２０（Ｐｓｅｕｄｏｍｏｎａｓ ｆｌｕｏｒｅｓｃｅｎｓ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−２（Ｃａｎｄｉｄａ ａｎｔａｒｃｔｉｃａ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−３（Ｃａｎｄｉｄａ ｒｕｇｏｓａ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−３ｐ（Ｃａｎｄｉｄａ ｒｕｇｏｓａ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−６（Ｐｓｅｕｄｏｍｏｎａｓ属由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−８（Ｔｈｅｒｍｏｍｙｃｅｓ ｌａｎｕｇｉｎｏｓ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−９（Ｒｈｙｚｏｍｕｃｏｒ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−１０（Ａｌｃａｌｉｇｅｎｅｓ属由来）等が挙げられる。
【００４５】
また、動物由来の酵素としては、例えば、天野エンザイム社パンクレアチン（豚由来）、ＳＩＧＭＡ社Ｐｏｒｃｉｎｅ Ｐａｎｃｒｅａｓ Ｌｉｐａｓｅ（豚由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−７（豚由来）等が、更に植物由来の代表的なものとしてＳＩＧＭＡ社Ｐａｐａｉｎ等が挙げられる。
【００４６】
本発明で使用する酵素としては、天野エンザイム社リパーゼＰ（Ｐｓｅｕｄｏｍｏｎａｓ属由来）、天野エンザイム社リパーゼＰＳ（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ由来）、天野エンザイム社リパーゼＰＳ−Ｃ ”Ａｍａｎｏ” Ｉ（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ由来）、天野エンザイム社リパーゼＰＳ−Ｃ ”Ａｍａｎｏ” ＩＩ（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ由来）、天野エンザイム社リパーゼＰＳ−Ｄ ”Ａｍａｎｏ” Ｉ（Ｐｓｅｕｄｏｍｏｎａｓ ｃｅｐａｃｉａ由来）、天野エンザイム社リパーゼＡＫ ”Ａｍａｎｏ”２０（Ｐｓｅｕｄｏｍｏｎａｓ ｆｌｕｏｒｅｓｃｅｎｓ由来）、天野エンザイム社リパーゼ ＡＹ（Ｃａｎｄｉｄａ ｒｕｇｏｓａ由来）、名糖産業社リパーゼＯＦ（Ｃａｎｄｉｄａ属由来）、名糖産業社リパーゼＰＬ（Ａｌｃａｌｉｇｅｎｅｓ属由来）、名糖産業社リパーゼＱＬＭ（Ａｌｃａｌｉｇｅｎｅｓ属由来）、名糖産業社リパーゼＳＬ（Ｂｕｒｋｈｏｌｄｅｒｉａ属由来）、名糖産業社リパーゼＴＬ（Ｐｓｅｕｄｏｍｏｎａｓ属由来）名糖産業社リパーゼＭＹ（Ｃａｎｄｉｄａ属由来）、ＮＯＶＯ社Ｎｏｖｏｚｙｍ４３５（Ｃａｎｄｉｄａ ａｎｔａｒｃｔｉｃａ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−２（Ｃａｎｄｉｄａ ａｎｔａｒｃｔｉｃａ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−６（Ｐｓｅｕｄｏｍｏｎａｓ属由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−９（Ｒｈｙｚｏｍｕｃｏｒ由来）、ロシュ社キラザイム（ＣＨＩＲＡＺＹＭＥ）Ｌ−１０（Ａｌｃａｌｉｇｅｎｅｓ属由来）が好ましい。
【００４７】
更に、前記のような単離された粗酵素または精製酵素のみならず、前記のエステル化またはエステル交換反応を触媒する能力を有する生体細胞またはその処理物をそのまま生体触媒として用いることもできる。生体細胞としては微生物、動物細胞、植物細胞を用いることができる。例えば、微生物を培養して得られる培養液をそのまま用いるか、または、培養液から遠心分離等の集菌操作によって得られる菌体またはその処理物等を用いることができる。菌体外に酵素が産生される場合は、遠心分離等の除菌操作を施した後の培養液をそのまま用いることもできるが、硫安、有機溶媒処理等の濃縮精製操作を実施することがより有効である。菌体処理物としては、アセトン、トルエン等で処理した菌体、凍結乾燥菌体、菌体破砕物、菌体を破砕した無細胞抽出物、これらから酵素を抽出した粗酵素液等が挙げられる。
【００４８】
このような微生物は特に限定されないが、例えば、シュードモナス（Ｐｓｅｕｄｏｍｏｎａｓ）属、アグロバクテリウム（Ａｇｒｏｂａｃｔｅｒｉｕｍ）属、バチルス（Ｂａｃｉｌｌｕｓ）属、ミクロバクテリウム（Ｍｉｃｒｏｂａｃｔｅｒｉｕｍ）属、アスペルギルス（Ａｓｐｅｒｇｉｌｌｕｓ）属、ムコール（Ｍｕｃｏｒ）属、リゾムコール（Ｒｈｙｚｏｍｕｃｏｒ）属、モルテエレラ（Ｍｏｒｔｉｅｒｅｌｌａ）属、ノカルデア（Ｎｏｃａｒｄｉａ）属、ステノトロフォモナス（Ｓｔｅｎｏｔｒｏｐｈｏｍｏｎａｓ）属、ブレブンディモナス（Ｂｒｅｖｕｎｄｉｍｏｎａｓ）属、ロドコッカス（Ｒｈｏｄｏｃｏｃｃｕｓ）属、エアロモナス（Ａｅｒｏｍｏｎａｓ）属、カンジダ（Ｃａｎｄｉｄａ）属、ピキア（Ｐｉｃｈｉａ）属、デバリオマイセス（Ｄｅｂａｒｙｏｍｙｃｅｓ）属、アルカリゲネス（Ａｌｃａｌｉｇｅｎｅｓ）属、フミコラ（Ｈｕｍｉｃｏｌａ）属、サーモマイセス（Ｔｈｅｒｍｏｍｙｃｅｓ）属、リゾプス（Ｒｈｉｚｏｐｕｓ）属に属する微生物が挙げられる。
【００４９】
また、これらの微生物の変異体、または目的の酵素遺伝子を単離し、通常の方法で各種宿主ベクター系に導入し、該ベクター系で形質転換した微生物を利用することも可能である。
【００５０】
本発明の反応を触媒する微生物は、例えば以下の方法によりスクリーニングすることができる。適当な栄養培地、例えば液体培地等を選択し、該培地により微生物を培養する。培養終了後、遠心分離等の操作を行い、培養菌体と培養上清を得る。それらを式（１）および式（２）で表される化合物を含む溶液に添加し、例えば３０℃で振とうする。反応終了後、ＧＣ（ガスクロマトグラフィー）により式（３）で表される化合物の有無を確認することにより、触媒活性の有無を確認する。
【００５１】
本発明において生体触媒を反応に供するに際しては、前記の触媒活性を示す限りその使用形態は特に限定されず、これら生体触媒を常法により適当な担体に固定化して用いることもできる。固定化は、例えば、架橋したアクリルアミドゲル、多糖類等で生体触媒を包括したり、または、イオン交換樹脂、珪藻土、セラミック等の固体担体に生体触媒を物理的、化学的に固定化することにより実施できる。生体触媒を固定化して用いることにより、触媒活性が上昇する場合がある。更に、反応終了後に生体触媒の分離、回収が容易になるため、生体触媒を再利用できるとともに、反応生成物の単離が容易になる。
【００５２】
また、これら生体触媒に、凍結乾燥もしくは真空乾燥等の処理を施すことにより、またはアセトン、メタノール、エタノール等の有機溶媒処理を施すことにより、該生体触媒の水分含有量を減じることができ、このように処理した生体触媒を使用すると反応が円滑に進行する場合が多い。
【００５３】
本発明では、通常これら生体触媒を１種類用いるが、同様な能力を有する２種類以上の生体触媒を混合して用いることも可能である。
【００５４】
本発明において、生体触媒源の一つである微生物の培養には、通常これらの微生物が生育し得るものであれば何れの培養条件でも採用できる。炭素源としては、例えば、グルコース、シュークロースやマルトース等の糖類、酢酸、クエン酸やフマル酸等の有機酸またはその塩、エタノールやグリセロール等のアルコール類等を使用できる。窒素源としては、例えば、ペプトン、肉エキス、酵母エキスやアミノ酸等の一般天然窒素源の他、各種無機アンモニウム塩、有機酸アンモニウム塩等が使用できる。その他、無機塩、微量金属塩、ビタミン等が必要に応じて適宜添加される。また、高い触媒活性を得るために、オリーブオイル、大豆油等を含有する培地、またはエステル結合もしくはアミド結合を持つ化合物等を含有する培地で培養することも有効である。
【００５５】
その培養は常法に従って行えばよく、例えば、ｐＨ４〜１０、温度１５〜４０℃の範囲にて好気的に６〜９６時間培養する方法が挙げられる。
【００５６】
式（３）で表される不飽和カルボン酸エステルの製造方法におけるエステル化またはエステル交換反応は、例えば、以下の方法で行うことができる。
【００５７】
前記生体触媒の存在下、原料である式（１）で表される化合物および式（２）で表される化合物を混合し、溶解または懸濁させる。そして、この溶液または懸濁液を、温度等の条件を制御しながら反応させる。
【００５８】
なお、原料である式（１）で表される化合物および式（２）で表される化合物は、生成物の用途および生体触媒反応であることを考慮すると、共に高純度であることが好ましく、夾雑不純物の混入を防ぐことは当然で、積極的に夾雑不純物を除去することがさらに好ましい。例えば、式（１）で表される化合物にその製造過程に生じた副生成物、無機塩等が含まれる場合は生体触媒反応を阻害しないレベルまでそれら夾雑物を除去することが望ましい。また、界面活性剤等の反応促進作用のある化合物を加えることで効率的に反応が進行する。
【００５９】
反応溶媒の使用は任意であり、必要に応じて適宜使用できる。反応溶媒を用いる場合、通常、無水の有機溶媒を使用するが、イオン交換水、緩衝液等の水性媒体を含んだ系でも反応を行うことができる。有機溶媒としては、例えば、メタノール、エタノール、プロパノール、イソプロパノール、ブタノール、イソブタノール、ｔ−ブチルアルコール、ｔ−アミルアルコール等のアルコール系溶媒、ペンタン、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素系溶媒、ベンゼン、トルエン、キシレン等の芳香族炭化水素系溶媒、塩化メチレン、クロロホルム、四塩化炭素、ジクロロエタン等のハロゲン化炭化水素系溶媒、ジエチルエーテル、ジイソプロピルエーテル、メチル−ｔ−ブチルエーテル、テトラヒドロフラン、ジオキサン等のエーテル系溶媒、酢酸エチル、酢酸プロピル、酢酸ブチル等のエステル系溶媒、アセトン、メチルエチルケトン、メチルイソブチルケトン等のケトン系溶媒、アセトニトリル、Ｎ，Ｎ−ジメチルホルムアミド、ジメチルスルホキシド等が挙げられる。これらのうち、ｔ−ブチルアルコール、ヘキサン、オクタン、ジイソプロピルエーテル、テトラヒドロフラン、ジオキサン、メチル−ｔ−ブチルエーテル、メチルエチルケトン、アセトニトリルが好ましい。また、これらの有機溶媒を水への溶解度以上に加えた２層系で反応を行うこともできる。
【００６０】
反応液中の両原料、すなわち式（１）で表される化合物および式（２）で表される化合物のモル比、濃度は任意であり、特に制限はない。反応溶媒を使用する場合、通常、両原料の各々の濃度は反応液の重量に対して０．１〜４０重量％の間である。生産性等を考慮すると、両原料とも０．５重量％以上の濃度で実施するのが好ましい。反応溶媒を使用しない場合は、後の処理等を考慮すると、式（２）で表される化合物を式（１）で表される化合物に対して過剰に用いる方が好ましく、式（１）で表される化合物に対して式（２）で表される化合物を１．１〜１０００倍当量使用することがより好ましい。
【００６１】
式（２）で表される化合物をアシルドナーとして複数種類用いることも可能である。
【００６２】
反応液中の生体触媒の濃度は、その使用形態および反応条件により適宜決定されるが、通常、反応液の重量の０．０１〜５０重量％であり、好ましくは０．０５〜２０重量％である。
【００６３】
その他の反応温度または反応時間等の条件は使用する原料、生体触媒の活性等により、適宜決定されるもので、一概に言えないが、通常は５〜８０℃で１時間〜１週間、好ましくは１０〜７０℃で１〜１２０時間という範囲で反応が終了する条件を適宜選択することが好ましい。
【００６４】
更に、エステル化またはエステル交換反応中で、生成する水またはアルコール、アルデヒド等を系外に留出しながら反応することが速度論的に好ましい。そのため、減圧下で本反応を実施することも有効である。また、副生するアルコール、水等と共沸組成を作る溶剤を添加してもよい。このような溶剤は特に限定されないが、例えば、メチルエチルケトン、メチルイソプロピルケトン、メチルイソブチルケトン、ｎ−ヘキサン、ｎ−ヘプタン、トルエン等が挙げられる。
【００６５】
以上のような原料仕込み条件、生体触媒濃度、温度、溶媒、反応時間およびその他の反応条件は、反応収率等を考慮して、目的とするモノマーが最も多く採取できる条件を選択することが望ましい。
【００６６】
また、式（３）で表される不飽和カルボン酸エステルのうち、そのアルコールの結合部分あるいはその他の炭素原子を不斉中心とする立体異性体が存在する場合があるが、原料の式（１）で表される化合物は、Ｒ体、Ｓ体もしくはエンド、エキソ体等の立体異性体またはそれら混合物のいずれであってもよい。また、適宜生体触媒を選択し、目的や用途に応じた任意の立体構造を持った不飽和カルボン酸エステルを製造することもできる。
【００６７】
不飽和カルボン酸エステルを反応終了後の反応液から単離する方法としては、例えば、蒸留、薄膜蒸留、抽出洗浄、カラム分離等の方法が挙げられる。具体的には、生体触媒を濾過等で除去後、反応液から反応溶媒および／または未反応物を留去し、次いで蒸留またはカラム精製等により不飽和カルボン酸エステルを単離する方法が例示できる。
【００６８】
【実施例】
以下、本発明を実施例により具体的に説明するが、本発明の範囲はこれらの実施例の範囲に限定されるものではない。実施例において、反応終了後の反応液中の目的生成物濃度は、ＦＩＤガスクロマトグラフ分析（カラム；ＤＢ−５（０．３２ｍｍ ＩＤ ｘ ３０ｍ，Ｊ＆Ｗ Ｓｃｉｅｎｔｉｆｉｃ））により定量した。
【００６９】
［実施例１］ ２−ｅｘｏ−メタクリロイルオキシ−４−オキサトリシクロ［４．２．１．０^３，７］ノナン−５−オン（式（５０）で表される化合物）の合成
ｔ−ブタノール（以下、ｔ−ＢｕＯＨと言う。）中、２−ｅｘｏ−ヒドロキシ−４−オキサトリシクロ［４．２．１．０^３，７］ノナン−５−オン（式（５１）で表される化合物）およびビニルメタクリレートをそれぞれ１．０％（Ｗ／Ｖ）および０．８％（Ｗ／Ｖ）になるように調製した。そこに表１に示した酵素を５％（Ｗ／Ｖ）になるように加え、３０℃で２４時間反応させた。表１に反応液中の２−ｅｘｏ−メタクリロイルオキシ−４−オキサトリシクロ［４．２．１．０^３，７］ノナン−５−オン濃度を示した。
【００７０】
【化１８】

【００７１】
【化１９】

【００７２】
【表１】

【００７３】
［実施例２］ ８−または９−メタクリロイルオキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物（式（５２）で表される化合物）の合成
ｔ−ＢｕＯＨ中、８−または９−ヒドロキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物（式（５３）で表される化合物）およびビニルメタクリレートをそれぞれ１．０％（Ｗ／Ｖ）および０．７３％（Ｗ／Ｖ）になるように調製した。そこに表２に示した酵素を５％（Ｗ／Ｖ）になるように加え、３０℃で２４時間反応させた。表２に反応液中の８−または９−メタクリロイルオキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物濃度を示した。
【００７４】
【化２０】

【００７５】
【化２１】

【００７６】
【表２】

【００７７】
［実施例３］ ８−または９−メタクリロイルオキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物（式（５２）で表される化合物）の合成
メチルメタクリレート中、８−または９−ヒドロキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物（式（５３）で表される化合物）を１．０％（Ｗ／Ｗ）になるように調製し、そこに表３に示した酵素を５％（Ｗ／Ｖ）になるように加え、３０℃で２４時間反応させた。表３に反応液中の８−または９−メタクリロイルオキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物濃度を示した。
【００７８】
【表３】

【００７９】
［実施例４］ ２−ｅｘｏ−メタクリロイルオキシ−４、９−ジオキサトリシクロ［４．２．１．０^３，７］ノナン−５−オン（式（５４）で表される化合物）の合成
ｔ−ＢｕＯＨ中、２−ｅｘｏ−ヒドロキシ−４、９−ジオキサトリシクロ［４．２．１．０^３，７］ノナン−５−オン（式（５５）で表される化合物）およびビニルメタクリレートをそれぞれ１．０％（Ｗ／Ｖ）および０．７９％（Ｗ／Ｖ）になるように調製した。そこに表４に示した酵素を５％（Ｗ／Ｖ）になるように加え、３０℃で２４時間反応させた。表４に反応液中の２−ｅｘｏ−メタクリロイルオキシ−４、９−ジオキサトリシクロ［４．２．１．０^３，７］ノナン−５−オン濃度を示した。
【００８０】
【化２２】

【００８１】
【化２３】

【００８２】
【表４】

【００８３】
［実施例５］ ２−ｅｘｏ−アクリロイルオキシ−４−オキサトリシクロ［４．２．１．０^３，７］ノナン−５−オン（式（５６）で表される化合物）の合成
ｔ−ＢｕＯＨ中、２−ｅｘｏ−ヒドロキシ−４−オキサトリシクロ［４．２．１．０^３，７］ノナン−５−オンおよびビニルアクリレートをそれぞれ１．０％（Ｗ／Ｖ）および０．７％（Ｗ／Ｖ）になるように調製した。そこに表５に示した酵素を５％（Ｗ／Ｖ）になるように加え、３０℃で２４時間反応させた。表５に反応液中の２−ｅｘｏ−アクリロイルオキシ−４−オキサトリシクロ［４．２．１．０^３，７］ノナン−５−オン濃度を示した。
【００８４】
【化２４】

【００８５】
【表５】

【００８６】
［実施例６］ ８−または９−アクリロイルオキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物（式（５７）で表される化合物）の合成
ｔ−ＢｕＯＨ中、８−または９−ヒドロキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物（式（５３）で表される化合物）およびビニルアクリレートをそれぞれ１．０％（Ｗ／Ｖ）および０．６４％（Ｗ／Ｖ）になるように調製した。そこに表６に示した酵素を５％（Ｗ／Ｖ）になるように加え、３０℃で２４時間反応させた。表６に反応液中の８−または９−アクリロイルオキシ−４−オキサトリシクロ［５．２．１．０^２，６］デカン−３−オン混合物濃度を示した。
【００８７】
【化２５】

【００８８】
【表６】

【００８９】
【発明の効果】
本発明によれば、酸触媒を使用せず、また穏和な条件でレジスト用等の嵩高い不飽和カルボン酸エステルを製造することができる。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for producing an unsaturated carboxylic acid ester useful as a raw material monomer such as a constituent resin for a resist.
[0002]
[Prior art]
A resist for fine processing by lithography is prepared from various materials. For example, a resist for semiconductor production is prepared by polymerizing one or more monomers and adding an additive, an acid generator, a solvent, and the like thereto. In these resists, it is necessary to minimize impurities according to the purpose. Therefore, it is preferable to minimize the generation of by-products in the production of a resist monomer. As a resist monomer, an unsaturated carboxylic acid ester of an alcohol having an alicyclic structure is known.
[0003]
As a general method for synthesizing an unsaturated carboxylic acid ester, an addition reaction of an alkene and (meth) acrylic acid is carried out under an acid catalyst, and dehydration of an alcohol and (meth) acrylic acid in the presence of a condensing agent or an acid catalyst. There are chemical synthesis methods such as esterification by reaction, ester exchange reaction between alcohol and ester, and esterification reaction with acid anhydride or acid chloride.
[0004]
Unsaturated carboxylic acid esters of alcohols having an alicyclic structure are sterically bulky and acid-decomposable, so that it is generally difficult to synthesize them by addition reaction, dehydration reaction, and transesterification reaction under an acid catalyst. it is conceivable that. For this reason, as in Patent Documents 1 to 4, usually, it is often synthesized by an esterification reaction with an acid chloride.
[0005]
On the other hand, esterification or transesterification by a biological catalyst having the ability to catalyze esterification or transesterification (hereinafter also referred to as biocatalyst) is widely known. In general, it is considered that it is difficult to use it for a transesterification reaction for producing a bulky monomer because of its high site selectivity. For this reason, there has been no example of applying a biocatalyst to the synthesis of a special monomer having a three-dimensional bulkiness such as a resist monomer.
[0006]
[Patent Document 1] JP-A-2000-26446
[0007]
[Patent Document 2] JP-A-2000-159758
[0008]
[Patent Document 3] JP-A-2001-64273
[0009]
[Patent Document 4] JP-A-2001-64325
[0010]
[Problems to be solved by the invention]
However, in the production method based on the chemical synthesis method, a large amount of by-products, added catalysts, and the like are mixed, and purification requires a large amount of labor. Therefore, a method for producing a bulky unsaturated carboxylic acid ester for use in resists and the like under a mild condition without using an acid catalyst is desired.
[0011]
Accordingly, an object of the present invention is to provide a method for producing a bulky unsaturated carboxylic acid ester for use as a resist under mild conditions without using an acid catalyst.
[0012]
[Means for Solving the Problems]
The present inventors have made intensive studies to solve the above problems, and as a result, found that the above problems can be solved by performing esterification or transesterification in the presence of a biocatalyst, and completed the present invention.
[0013]
That is, the present invention provides a compound represented by the formula (1) or a compound represented by the formula (1) having a substituent in the presence of a biologically-derived catalyst having an ability to catalyze an esterification or transesterification reaction; This is a method for producing an unsaturated carboxylic acid ester represented by the formula (3) or a formula (3) having a substituent by reacting a compound represented by the formula (1) with an esterification or transesterification reaction.
[0014]
Embedded image

(Where R ¹ Is hydrogen or an acyl group having 1 to 6 carbon atoms, X ¹ Represents -C (O)-, -OC (O)-, -C (O) -O- or -C (O) -OC (O)-, wherein a and b are each 0 to 2; And Z represents a cyclic saturated hydrocarbon group which may have a substituent. The methylene group in the cyclic skeleton of Z may be replaced by an oxygen atom or a sulfur atom. )
[0015]
Embedded image

(R ² Represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a substituent; ³ Represents a hydrogen atom or a substituent. )
[0016]
Embedded image

(Where Z, X ¹ , A and b have the same meanings as in the above formula (1), ² Has the same meaning as in the above formula (2). )
[0017]
BEST MODE FOR CARRYING OUT THE INVENTION
In the present invention, the unsaturated carboxylic acid ester represented by the formula (3) or the formula (3) having a substituent (hereinafter, these are collectively referred to as an unsaturated carboxylic acid ester represented by the formula (3). ) Is a compound represented by the above formula (1) or a formula (1) having a substituent (hereinafter collectively referred to as a compound represented by the formula (1)) in the presence of a biological catalyst having an ability to catalyze an esterification or transesterification reaction. (Also referred to as a compound represented by (1)) and a compound represented by the formula (2).
[0018]
In equation (1), X ¹ A ring structure containing ¹ Is -C (O)-, a cyclic ketone, -OC (O)-or -C (O) -O-, lactone, -C (O) -OC (O)- Is an acid anhydride. Since there are few side reactions during the reaction or purification, X ¹ Is preferably -C (O)-, -OC (O)-or -C (O) -O-. Further, from the viewpoint of reactivity, X ¹ Is preferably -OC (O)-or -C (O) -O-.
[0019]
In the formula (1), R ¹ Is hydrogen or an acyl group having 1 to 6 carbon atoms. Examples of the acyl group having 1 to 6 carbon atoms include a formyl group, an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, and an isovaleryl group. In terms of reactivity, R ¹ Are preferably a hydrogen atom, a formyl group, and an acetyl group.
[0020]
In the formula (1), R ¹ The group represented by O may be plural. R ¹ When there are a plurality of groups represented by O, depending on the type and number of the biocatalyst used, a specific R ¹ Only the group represented by O is esterified or transesterified, ¹ The group represented by O can be esterified or transesterified.
[0021]
In the formula (1), a and b are each an integer of 0 to 2. a and b are each preferably 0 or 1. From the viewpoint of the stability of the starting materials and products during the reaction or purification, a + b is represented by X ¹ Is preferably 1 to 2 when is -C (O)-, and is preferably 0 to 2 when -C (O)-or -C (O) -O-, and -C (O) -O- In the case of C (O)-, 0 to 1 is preferable.
[0022]
In the formula (1), Z is a cyclic saturated hydrocarbon group which may have a substituent, and may be either a monocyclic saturated hydrocarbon group or a polycyclic saturated hydrocarbon group. Examples of the polycyclic saturated hydrocarbon group include a condensed polycyclic saturated hydrocarbon group, a bridged cyclic saturated hydrocarbon group, a spiro saturated hydrocarbon group, and groups containing these groups. Z is a polycyclic saturated carbon in view of the thermal stability and dry etching resistance of the polymer required as a raw material for the resist component resin of the compound represented by the formula (3) obtained by the method of the present invention. Hydrogen groups are preferred, and bridged cyclic saturated hydrocarbon groups are more preferred.
[0023]
Examples of the first substituent in the compound represented by the formula (1) having a substituent (hereinafter, referred to as a first substituent) include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, and an isobutyl group. Alkyl group having 1 to 6 carbon atoms such as a group, sec-butyl group, tert-butyl group, tert-amyl group, n-pentyl group, n-hexyl group; and 2 carbon atoms such as vinyl group, propenyl group and butenyl group. An alkenyl group having 2 to 6 carbon atoms such as an ethynyl group, a propynyl group, a butynyl group, a pentynyl group, and a hexynyl group; An alkoxy group; an alkylthio group having 1 to 4 carbon atoms such as a methylthio group, an ethylthio group, a propylthio group, and a butylthio group; a formamide group, an acetamido group, and a propion An amide group having 1 to 7 carbon atoms such as an amide group and a hexaneamide group; a cyano group; an acyl group having 1 to 4 carbon atoms such as a formyl group, an acetyl group, a propionyl group, and a butyryl group; a methoxycarbonyl group, an ethoxycarbonyl group; An alkoxycarbonyl group having 2 to 4 carbon atoms such as a propoxycarbonyl group; an aralkyl group such as a benzyl group, a phenethyl group, a naphthylmethyl group; a methylamino group, a dimethylamino group, an ethylamino group, a propylamino group, a butylamino group; Examples of the substituent include an amino group having an alkyl group having 1 to 4 carbon atoms; a nitro group; and a substituent such as a thiol group or a substituent derived therefrom. Substituents such as the above-mentioned alkyl group, alkenyl group, alkynyl group, alkoxy group, alkylthio group, amide group, acyl group, alkoxycarbonyl group, aralkyl group, and amino group having an alkyl group are the second groups such as halogen. It may have a substituent. As the second substituent, an alkyl group having 1 to 6 carbon atoms is preferable, and a methyl group and an ethyl group are more preferable.
[0024]
Further, the methylene group constituting the cyclic skeleton of Z may be replaced by an oxygen atom or a sulfur atom. R ¹ The following formulas (8) to (25) are specific examples of OZ.
[0025]
Embedded image

(Where R ¹ Has the same meaning as in formula (1). )
[0026]
Further, from the viewpoint of reactivity to the addition reaction of the compound represented by the formula (1), R ¹ As OZ, a cyclic saturated hydrocarbon group represented by the formula (4) is preferable.
[0027]
Embedded image

(Where R ¹ Has the same meaning as in formula (1), ⁴ ~ R ⁹ Represents a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms when independently. Also, R ⁴ ~ R ⁹ May be together a methylene chain having 1 to 6 carbon atoms. Hydrogen in the methylene chain may be substituted by an alkyl group having 1 to 2 carbon atoms, and may have -O- or -S- in the middle of the methylene chain. Further, R ⁴ And R ⁵ May together be -O- or -S-. )
[0028]
Examples of the linear or branched alkyl group having 1 to 6 carbon atoms in the formula (4) include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, a tert-butyl group, and a tert. -Amyl group, n-pentyl group, n-hexyl group and the like.
[0029]
Examples of the methylene chain having 1 to 6 carbon atoms having -O- and -S- in the formula (4) include, for example, -CH ₂ -O-CH ₂ -, -CH ₂ -O- (CH ₂ ) ₂ -, -CH ₂ -O- (CH ₂ ) ₃ -, -CH ₂ -O- (CH ₂ ) ₄ -, -CH ₂ -O- (CH ₂ ) ₅ -,-(CH ₂ ) ₂ -O- (CH ₂ ) ₂ -,-(CH ₂ ) ₂ -O- (CH ₂ ) ₃ -,-(CH ₂ ) ₂ -O- (CH ₂ ) ₄ -,-(CH ₂ ) ₃ -O- (CH ₂ ) ₃ -, -CH ₂ -S-CH ₂ -, -CH ₂ -S- (CH ₂ ) ₂ -, -CH ₂ -S- (CH ₂ ) ₃ -, -CH ₂ -S- (CH ₂ ) ₄ -, -CH ₂ -S- (CH ₂ ) ₅ -,-(CH ₂ ) ₂ -S- (CH ₂ ) ₂ -,-(CH ₂ ) ₂ -S- (CH ₂ ) ₃ -,-(CH ₂ ) ₂ -S- (CH ₂ ) ₄ -,-(CH ₂ ) ₃ -S- (CH ₂ ) ₃ -And the like.
[0030]
Specific examples of the cyclic saturated hydrocarbon group represented by the formula (4) include the following formulas (26) to (43).
[0031]
Embedded image

[0032]
Further, as the compound represented by the formula (1), a compound represented by the formula (6) or a formula (6) having a linear or branched alkyl group having 1 to 6 carbon atoms as a substituent (hereinafter, these are referred to as Are collectively referred to as a compound represented by the formula (6)).
[0033]
Embedded image

(Where R ¹ Is synonymous with formula (1), and X ² Represents -OC (O)-or -C (O) -O-, c and d each represent an integer of 0 or 1, and W represents -CH ₂ Represents-or -O-. )
[0034]
Examples of the compound represented by the formula (6) include compounds of the following formulas (44) to (49) and compounds of the formulas (44) to (49) having a linear or branched alkyl group having 1 to 6 carbon atoms. Is mentioned. From the viewpoints of reactivity and target product selectivity, the compounds represented by formulas (44) to (46) and isomers such as geometric isomers, optical isomers or enantiomers thereof are particularly preferred.
[0035]
Embedded image

[0036]
The compound represented by the formula (1) is described in J. Am. Chem. Soc. , Perkin Trans. 1 (1996), 2309-2313; Chem. Soc. , (1959), 221-226, JP-A-2001-188351, WO02 / 46179, JP-A-2000-159758, and the like.
[0037]
In the compound represented by the formula (2) used for esterification or transesterification with the above compound, ² Is a hydrogen atom or a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a t-butyl group, and the alkyl group may have a substituent such as halogen. R ² Is preferably a hydrogen atom or a methyl group. Also, R ³ Is a hydrogen atom or a substituent. Examples of the substituent include an alkyl group having 1 to 6 carbon atoms such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a pentyl group and a hexyl group. An alkenyl group having 2 to 6 carbon atoms such as vinyl group, propenyl group, butenyl group, pentenyl group and hexenyl group; an alkynyl group having 2 to 6 carbon atoms such as ethynyl group, propynyl group, butynyl group, pentynyl group and hexynyl group. And aralkyl groups such as a benzyl group, a phenethyl group and a naphthylmethyl group. Substituents such as the alkyl group, alkenyl group, alkynyl group, aralkyl group and the like are an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an amide group having 1 to 4 carbon atoms, It may have a substituent such as an acyl group and a cyano group of No. 4. R ³ Is preferably a hydrogen atom, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a vinyl group, a 1-methoxyvinyl group, or a 1-ethoxyvinyl group.
[0038]
By reacting the compound represented by the formula (1) with the compound represented by the formula (2) in the presence of a biocatalyst and performing an esterification or transesterification reaction, the compound represented by the formula (3) is obtained. Unsaturated carboxylic esters can be produced.
[0039]
Also, R ¹ Reacting a compound represented by the formula (1) in which OZ is the formula (4) with a compound represented by the formula (2) in the presence of a biocatalyst to perform an esterification or transesterification reaction; Thus, the unsaturated carboxylic acid ester represented by the formula (5) can be produced.
[0040]
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(Where X ¹ Has the same meaning as in formula (1), ² Has the same meaning as in formula (2), ⁴ ~ R ⁹ Is synonymous with formula (4). )
[0041]
Further, by reacting the compound represented by the formula (6) with the compound represented by the formula (2) in the presence of a biocatalyst to perform an esterification or transesterification reaction, the compound represented by the formula (7) is obtained. Unsaturated carboxylic acid esters can be produced.
[0042]
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(Where R ² Has the same meaning as in formula (2), and X ² , W, c, and d have the same meanings as in equation (6). )
[0043]
The type and origin of the biocatalyst used in the present invention is not particularly limited, as long as it is derived from a living body having the ability to catalyze the esterification or transesterification reaction. Among them, enzymes having hydrolytic activities such as lipase activity, esterase activity, protease activity and amidase activity are particularly preferred.
[0044]
Examples of microorganism-derived enzymes include, for example, Amano Enzyme Lipase P (derived from Pseudomonas sp.), Amano Enzyme Lipase PS (derived from Pseudomonas cepacia), Amano Enzyme Lipase A6 (derived from Aspergillus), and Amano Enzyme Lipase APilAusPusAil. Lipase M-10 (derived from Mucor genus), Meito Sangyo Co., Ltd. lipase OF (derived from Candida), Meito Sangyo Co., Ltd. lipase PL (derived from genus Alcaligenes), Meito Sangyo Co., Ltd. ), Meito Sangyo Co., Ltd. Lipase SL (derived from the genus Burkholderia), Meito Sangyo Co., Ltd. lipase TL (derived from the genus Pseudomonas), Meito Sangyo Co., Ltd. Lipase MY (from the genus Candida) ), Toyobo Team LIP (from Pseudomonas genus), Lipase Type VII from SIGMA (from Candida rugosa), Acylase I from SIGMA (from Aspergilus Limex melexus), SIGMA from ProteXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXeXiXiXiYYYYYYYYYYYYYYYYI ToYZYM LIP (from Pseudomonas genus), SIGMA's Lipase Type VII (from Candida rugosa), SIGMA's Acylase I (from Aspergillus melaseus) antarctica), NOVO Lipozyme IM 20 (from Humicola lanuginosa), Amano Enzyme lipase M (from Mucor javanicus), Amano Enzyme lipase MFL, NOVO Novozym RicaVidMidOntVicaMidVaidZipVadMicVadMicVidMidVaidZipVicMidVadMicVidMicVidMidVaidMicVidMidVaidMicVidMidVaidMicVidMidVaidMicVidOmicaVipMicVidAmpicVidMicVipAmpicaV lipozyme 435. IM (derived from Rhizomucor miehei), NOVO LipozymeTL IM (derived from Thermomyces lanuginusus), NOVO Alcalase (derived from Bacillus licheniformisBacillusBacillusBacillusBac) Origin), Nagase Seikagaku Bio-Prase Conc (from Bacillus subtilis), Amano Enzyme lipase AY (from Candida rugosa), Nagase Biochemical Co., Ltd. lipase A-10 (from Rhizopus japonicus), Nagase Biochemical 2G (from Pseudomonas sp.), Na Bioseparation Bioseparase AL-15FG (from Bacillus subtilis), Lipase PS-C "Amano" I from Amano Enzyme (from Pseudomonas cepacia), Lipase PS-C "Amano" II from Amano Enzyme (Pseudomas) II (Pseudomas) Enzyme lipase PS-D "Amano" I (from Pseudomonas cepacia), Amano Enzyme lipase AK "Amano" 20 (from Pseudomonas fluorescens), Roche's Kirazyme (CHIRAZYME) Lacciant Laccia (CHIRAZYME) Lacciant CHIRAZYME) L-3 (from Candida rugosa), Roche Kirazyme (From Candida rugosa) (CHIRAZYME) L-3p, Roche Chirazyme (CHIRAZYME) L-6 (Pseudomonas genus), Roche Chirazyme (Chirazyme) L-8 (from Thermomyces Lanuginos), Roche Chirazyme (Chirazyme) L- 9 (derived from Rhyzomucor) and Roche Kirazyme L-10 (derived from the genus Alcaligenes).
[0045]
Examples of animal-derived enzymes include, for example, Amano Enzyme Pancreatin (porcine), SIGMA Porcine Pancreas Lipase (porcine), Roche Kirazyme (CHIRAZYME) L-7 (porcine), and plant-derived enzymes. Representative examples include SIGMA Papain.
[0046]
The enzymes used in the present invention include Amano Enzyme Lipase P (derived from the genus Pseudomonas), Amano Enzyme Lipase PS (derived from Pseudomonas cepacia), and Amano Enzyme Lipase PS-C "Amano" I (derived from Pseudomonas cepazyme). Company lipase PS-C "Amano" II (Pseudomonas cepacia derived), Amano enzyme Inc. lipase PS-D "Amano" I (from Pseudomonas cepacia), Amano enzyme Inc. lipase AK "Amano" 20 (derived from Pseudomonas fluorescens), Amano enzyme Inc. Lipase AY (from Candida rugosa), Meito Sangyo Co., Ltd. Lipase OF (from Candida genus) Meiji Sangyo Co., Ltd. lipase PL (derived from the genus Alcaligenes), Meito Sangyo Co., Ltd. lipase QLM (derived from the genus Alcaligenes), Meito Sangyo Co., Ltd. lipase SL (derived from the genus Burkholderia), Meito Sangyo Co., Ltd. Lipase TL (derived from the genus Pseudomonas) Sangyosha Lipase MY (from Candida genus), NOVO Novozym435 (from Candida antarctica), Roche Kirazyme (CHIRAZYME) L-2 (Candida antarctica), Roche Kirazym (CHIRAZYME, CHIRAZMEP) KIRAZYME L-9 (from Rhyzomucor), Roche KIRAZYME L-10 (Alcaligen) s derived from the genus) are preferred.
[0047]
Further, not only the isolated crude enzyme or the purified enzyme as described above, but also a living cell having the ability to catalyze the above-mentioned esterification or transesterification reaction or a processed product thereof can be used as it is as a biocatalyst. Microorganisms, animal cells, and plant cells can be used as living cells. For example, a culture solution obtained by culturing a microorganism can be used as it is, or a cell obtained by a cell collection operation such as centrifugation from the culture solution or a processed product thereof can be used. When the enzyme is produced outside the cells, the culture solution after eradication operation such as centrifugation can be used as it is, but it is more preferable to carry out concentration and purification operations such as ammonium sulfate and organic solvent treatment. It is valid. Examples of the treated cells include cells treated with acetone, toluene, etc., freeze-dried cells, crushed cells, cell-free extracts obtained by crushing cells, and crude enzyme solutions obtained by extracting enzymes from these cells. .
[0048]
Such microorganisms are not particularly limited, but for example, Pseudomonas, Agrobacterium, Bacillus, Microbacterium, Aspergillus, and Mucor. Genus, Rhyzomucor, Mortierella, Nocardia, Stenotrophomonas, Brebundimonas, Rhodocos, Rhodococcus, Rhodococcos, Rhodococcus, Rhodococca, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus, Rhodococcus rhoda Genus (Candida), Genus Pichia, Deva Omaisesu (Debaryomyces) genus Alcaligenes (Alcaligenes) genus Humicola (Humicola) genus Thermomyces (Thermomyces) genus include microorganisms belonging to Rhizopus (Rhizopus) genus.
[0049]
Further, it is also possible to isolate mutants of these microorganisms or target enzyme genes, introduce them into various host vector systems by an ordinary method, and use microorganisms transformed with the vector systems.
[0050]
Microorganisms that catalyze the reaction of the present invention can be screened, for example, by the following method. An appropriate nutrient medium, such as a liquid medium, is selected, and the microorganism is cultured in the medium. After the completion of the culture, operations such as centrifugation are performed to obtain cultured cells and a culture supernatant. They are added to a solution containing the compounds represented by the formulas (1) and (2) and shaken, for example, at 30 ° C. After completion of the reaction, the presence or absence of the compound represented by the formula (3) is confirmed by GC (gas chromatography) to confirm the presence or absence of the catalytic activity.
[0051]
When the biocatalyst is subjected to the reaction in the present invention, the form of use is not particularly limited as long as it exhibits the above-mentioned catalytic activity, and these biocatalysts can be immobilized on a suitable carrier by a conventional method and used. Immobilization is, for example, by encapsulating the biocatalyst with a crosslinked acrylamide gel, polysaccharide, or the like, or by physically and chemically immobilizing the biocatalyst on a solid carrier such as an ion exchange resin, diatomaceous earth, and ceramic. Can be implemented. Immobilization of the biocatalyst may increase the catalytic activity in some cases. Further, since the separation and recovery of the biocatalyst after the reaction is completed, the biocatalyst can be reused and the reaction product can be easily isolated.
[0052]
Further, by subjecting these biocatalysts to a treatment such as freeze-drying or vacuum drying, or to an organic solvent treatment such as acetone, methanol, and ethanol, the water content of the biocatalyst can be reduced. When a biocatalyst treated as described above is used, the reaction often proceeds smoothly.
[0053]
In the present invention, one kind of these biocatalysts is usually used, but two or more kinds of biocatalysts having the same ability can be mixed and used.
[0054]
In the present invention, for culturing microorganisms, which are one of the biocatalyst sources, any culturing conditions can be employed as long as these microorganisms can grow normally. Examples of the carbon source include sugars such as glucose, sucrose and maltose, organic acids such as acetic acid, citric acid and fumaric acid or salts thereof, and alcohols such as ethanol and glycerol. As the nitrogen source, for example, various inorganic ammonium salts, organic acid ammonium salts and the like can be used in addition to general natural nitrogen sources such as peptone, meat extract, yeast extract and amino acids. In addition, inorganic salts, trace metal salts, vitamins and the like are added as needed. In order to obtain high catalytic activity, it is also effective to culture in a medium containing olive oil, soybean oil, or the like, or a medium containing a compound having an ester bond or an amide bond.
[0055]
The cultivation may be performed according to a conventional method, for example, a method of culturing aerobically for 6 to 96 hours at pH 4 to 10 and temperature of 15 to 40 ° C.
[0056]
The esterification or transesterification in the method for producing the unsaturated carboxylic acid ester represented by the formula (3) can be performed, for example, by the following method.
[0057]
In the presence of the biocatalyst, the raw material compound represented by the formula (1) and the compound represented by the formula (2) are mixed and dissolved or suspended. Then, the solution or suspension is reacted while controlling conditions such as temperature.
[0058]
The compounds represented by the formula (1) and the compound represented by the formula (2), which are raw materials, are preferably both highly pure in consideration of the use of the product and the fact that it is a biocatalytic reaction. Naturally, it is more preferable to positively remove the impurities. For example, when the compound represented by the formula (1) contains by-products, inorganic salts, and the like generated during the production process, it is desirable to remove such contaminants to a level that does not inhibit the biocatalytic reaction. Further, the reaction proceeds efficiently by adding a compound having a reaction promoting action such as a surfactant.
[0059]
The use of a reaction solvent is optional, and can be used as needed. When a reaction solvent is used, usually, an anhydrous organic solvent is used, but the reaction can also be performed in a system containing an aqueous medium such as ion-exchanged water and a buffer. Examples of the organic solvent include alcohol solvents such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, t-butyl alcohol, and t-amyl alcohol; and aliphatic hydrocarbon solvents such as pentane, hexane, heptane, and octane. Benzene, toluene, xylene and other aromatic hydrocarbon solvents, methylene chloride, chloroform, carbon tetrachloride, halogenated hydrocarbon solvents such as dichloroethane, diethyl ether, diisopropyl ether, methyl-t-butyl ether, tetrahydrofuran, dioxane, etc. Ether solvents, ester solvents such as ethyl acetate, propyl acetate and butyl acetate, ketone solvents such as acetone, methyl ethyl ketone and methyl isobutyl ketone, acetonitrile, N, N-dimethylformamide Dimethyl sulfoxide and the like. Of these, t-butyl alcohol, hexane, octane, diisopropyl ether, tetrahydrofuran, dioxane, methyl-t-butyl ether, methyl ethyl ketone, and acetonitrile are preferred. In addition, the reaction can be carried out in a two-layer system in which these organic solvents are added to the solubility in water or higher.
[0060]
The molar ratio and concentration of both raw materials in the reaction solution, that is, the compound represented by the formula (1) and the compound represented by the formula (2) are arbitrary and are not particularly limited. When a reaction solvent is used, the concentration of each of the raw materials is usually between 0.1 and 40% by weight based on the weight of the reaction solution. In consideration of productivity and the like, it is preferable to carry out both raw materials at a concentration of 0.5% by weight or more. When the reaction solvent is not used, it is preferable to use the compound represented by the formula (2) in excess of the compound represented by the formula (1) in consideration of the subsequent treatment and the like. It is more preferable to use the compound represented by the formula (2) in an amount of 1.1 to 1000 times equivalent to the compound represented.
[0061]
It is also possible to use a plurality of compounds represented by the formula (2) as an acyl donor.
[0062]
The concentration of the biocatalyst in the reaction solution is appropriately determined depending on its use form and reaction conditions, but is usually 0.01 to 50% by weight, preferably 0.05 to 20% by weight of the weight of the reaction solution. is there.
[0063]
Other conditions such as the reaction temperature or the reaction time are appropriately determined depending on the raw materials to be used, the activity of the biocatalyst, and the like, and cannot be specified unconditionally, but are usually 5 to 80 ° C. for 1 hour to 1 week, preferably It is preferable to appropriately select the conditions under which the reaction is completed at a temperature of 10 to 70 ° C. for 1 to 120 hours.
[0064]
Furthermore, it is kinetically preferable to react while distilling out generated water, alcohol, aldehyde and the like out of the system during the esterification or transesterification reaction. Therefore, it is also effective to carry out this reaction under reduced pressure. Further, a solvent that forms an azeotropic composition with alcohol, water, and the like as a by-product may be added. Such a solvent is not particularly limited, and examples thereof include methyl ethyl ketone, methyl isopropyl ketone, methyl isobutyl ketone, n-hexane, n-heptane, and toluene.
[0065]
As for the raw material charging conditions, the biocatalyst concentration, the temperature, the solvent, the reaction time and other reaction conditions, it is desirable to select conditions under which the target monomer can be collected most in consideration of the reaction yield and the like. .
[0066]
In addition, among the unsaturated carboxylic acid esters represented by the formula (3), there may be a stereoisomer having an asymmetric center at a bonding portion of the alcohol or another carbon atom. The compound represented by the formula (1) may be an R-form, an S-form, an endo-form, an exo-form or other stereoisomers, or a mixture thereof. In addition, it is also possible to select an appropriate biocatalyst and produce an unsaturated carboxylic acid ester having an arbitrary steric structure according to the purpose or use.
[0067]
Methods for isolating the unsaturated carboxylic acid ester from the reaction solution after the reaction include, for example, methods such as distillation, thin-film distillation, extraction washing, and column separation. Specifically, a method of removing the biocatalyst by filtration or the like, distilling the reaction solvent and / or unreacted substances from the reaction solution, and then isolating the unsaturated carboxylic acid ester by distillation or column purification can be exemplified. .
[0068]
【Example】
Hereinafter, the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited to the Examples. In Examples, the concentration of the target product in the reaction solution after the completion of the reaction was quantified by FID gas chromatography (column: DB-5 (0.32 mm ID x 30 m, J & W Scientific)).
[0069]
[Example 1] 2-exo-methacryloyloxy-4-oxatricyclo [4.2.1.0 ^3,7 Synthesis of Nonan-5-one (Compound Represented by Formula (50))
In t-butanol (hereinafter referred to as t-BuOH), 2-exo-hydroxy-4-oxatricyclo [4.2.1.0]. ^3,7 Nonan-5-one (compound represented by the formula (51)) and vinyl methacrylate were prepared to be 1.0% (W / V) and 0.8% (W / V), respectively. The enzymes shown in Table 1 were added thereto to a concentration of 5% (W / V) and reacted at 30 ° C. for 24 hours. Table 1 shows 2-exo-methacryloyloxy-4-oxatricyclo [4.2.1.0 in the reaction solution. ^3,7 Nonan-5-one concentration was shown.
[0070]
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[0071]
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[0072]
[Table 1]

[0073]
Example 2 8- or 9-methacryloyloxy-4-oxatricyclo [5.2.1.0 ^2,6 Synthesis of decane-3-one mixture (compound represented by formula (52))
8- or 9-Hydroxy-4-oxatricyclo [5.2.1.0 in t-BuOH ^2,6 A decane-3-one mixture (the compound represented by the formula (53)) and vinyl methacrylate were prepared to be 1.0% (W / V) and 0.73% (W / V), respectively. The enzymes shown in Table 2 were added thereto to a concentration of 5% (W / V) and reacted at 30 ° C. for 24 hours. Table 2 shows 8- or 9-methacryloyloxy-4-oxatricyclo [5.2.1.0] in the reaction solution. ^2,6 ] The concentration of the decane-3-one mixture was indicated.
[0074]
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[0075]
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[0076]
[Table 2]

[0077]
Example 3 8- or 9-methacryloyloxy-4-oxatricyclo [5.2.1.0 ^2,6 Synthesis of decane-3-one mixture (compound represented by formula (52))
8- or 9-hydroxy-4-oxatricyclo [5.2.1.0 in methyl methacrylate ^2,6 A decane-3-one mixture (compound represented by the formula (53)) was prepared to be 1.0% (W / W), and the enzyme shown in Table 3 was added thereto at 5% (W / V). ) And reacted at 30 ° C. for 24 hours. Table 3 shows that 8- or 9-methacryloyloxy-4-oxatricyclo [5.2.1.0 in the reaction solution. ^2,6 ] The concentration of the decane-3-one mixture was indicated.
[0078]
[Table 3]

[0079]
Example 4 2-exo-methacryloyloxy-4,9-dioxatricyclo [4.2.1.0 ^3,7 Synthesis of Nonan-5-one (Compound Represented by Formula (54))
In tert-BuOH, 2-exo-hydroxy-4,9-dioxatricyclo [4.2.1.0 ^3,7 Nonan-5-one (compound represented by formula (55)) and vinyl methacrylate were prepared to be 1.0% (W / V) and 0.79% (W / V), respectively. The enzymes shown in Table 4 were added thereto to a concentration of 5% (W / V) and reacted at 30 ° C. for 24 hours. Table 4 shows that 2-exo-methacryloyloxy-4,9-dioxatricyclo [4.2.1.0 in the reaction solution. ^3,7 Nonan-5-one concentration was shown.
[0080]
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[0081]
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[0082]
[Table 4]

[0083]
Example 5 2-exo-acryloyloxy-4-oxatricyclo [4.2.1.0 ^3,7 Synthesis of Nonan-5-one (Compound Represented by Formula (56))
2-exo-hydroxy-4-oxatricyclo [4.2.1.0 in t-BuOH ^3,7 Nonan-5-one and vinyl acrylate were prepared to be 1.0% (W / V) and 0.7% (W / V), respectively. The enzymes shown in Table 5 were added thereto to a concentration of 5% (W / V) and reacted at 30 ° C. for 24 hours. Table 5 shows 2-exo-acryloyloxy-4-oxatricyclo [4.2.1.0] in the reaction solution. ^3,7 Nonan-5-one concentration was shown.
[0084]
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[0085]
[Table 5]

[0086]
Example 6 8- or 9-acryloyloxy-4-oxatricyclo [5.2.1.0 ^2,6 Synthesis of decane-3-one mixture (compound represented by formula (57))
8- or 9-Hydroxy-4-oxatricyclo [5.2.1.0 in t-BuOH ^2,6 A decane-3-one mixture (the compound represented by the formula (53)) and vinyl acrylate were prepared to be 1.0% (W / V) and 0.64% (W / V), respectively. The enzymes shown in Table 6 were added thereto to a concentration of 5% (W / V) and reacted at 30 ° C. for 24 hours. Table 6 shows 8- or 9-acryloyloxy-4-oxatricyclo [5.2.1.0] in the reaction solution. ^2,6 ] The concentration of the decane-3-one mixture was indicated.
[0087]
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[0088]
[Table 6]

[0089]
【The invention's effect】
ADVANTAGE OF THE INVENTION According to this invention, a bulky unsaturated carboxylic acid ester for resists etc. can be manufactured under mild conditions, without using an acid catalyst.

Claims (4)

A compound represented by the formula (1) or a compound represented by the formula (1) having a substituent and a compound represented by the formula (2) in the presence of a biological catalyst having an ability to catalyze an esterification or transesterification reaction. And performing an esterification or transesterification reaction to produce an unsaturated carboxylic acid ester represented by the formula (3) or the formula (3) having a substituent.

(Wherein, R ¹ is hydrogen or an acyl group having 1 to 6 carbon atoms, X ¹ is —C (O) —, —OC (O) —, —C (O) —O—, or —C (O A) and b each represent an integer of 0 to 2, and Z represents a cyclic saturated hydrocarbon group which may have a substituent. May be replaced by an oxygen atom or a sulfur atom.)

(R ² represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a substituent, and R ³ represents a hydrogen atom or a substituent.)

(In the formula, Z, X ¹ , a, and b have the same meanings as in the formula (1), and R ² has the same meaning as in the formula (2).) In the formulas (1) and (3), Z is an optionally substituted 5 to 18 polycyclic saturated hydrocarbon group, and the methylene group in the cyclic skeleton of Z is an oxygen atom or The method for producing an unsaturated carboxylic acid ester according to claim 1, wherein the unsaturated carboxylic acid ester may be replaced with a sulfur atom. In the formula (1), R ¹ O-Z is a cyclic saturated hydrocarbon group represented by the following formula (4), and the produced unsaturated carboxylic acid ester is a compound represented by the formula (5) The method for producing an unsaturated carboxylic acid ester according to claim 1, wherein

(Wherein, R ¹ has the same meaning as in formula (1), and R ^{4 to} R ⁹ independently represent a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms. ^{4 to} R ⁹ may be taken together to form a methylene chain having 1 to 6 carbon atoms, wherein hydrogen of the methylene chain may be substituted by an alkyl group having 1 to 2 carbon atoms. And R ⁴ and R ⁵ may be taken together to be —O— or —S—.

(Wherein, X ¹ has the same meaning as in formula (1), R ² has the same meaning as in formula (2), and R ^{4 to} R ⁹ have the same meaning as in formula (4).) The compound of the formula (1) is a compound represented by the formula (6), and the produced unsaturated carboxylic acid ester is a compound represented by the formula (7). The method for producing an unsaturated carboxylic acid ester of the above.

(Wherein, R ¹ has the same meaning as in formula (1), X ² represents —OC (O) — or —C (O) —O—, and c and d each represent an integer of 0 or 1. represents, W is -CH ₂ - represents a or -O-).

(Wherein, R ² has the same meaning as in formula (2), and X ² , W, c, and d have the same meaning as in formula (6).)