JP5157154B2 - 4 '-(alkoxycarbonyl) bicyclohexyl-4-ylcarboxylic acid and process for producing the same - Google Patents

4 '-(alkoxycarbonyl) bicyclohexyl-4-ylcarboxylic acid and process for producing the same Download PDF

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JP5157154B2
JP5157154B2 JP2006342612A JP2006342612A JP5157154B2 JP 5157154 B2 JP5157154 B2 JP 5157154B2 JP 2006342612 A JP2006342612 A JP 2006342612A JP 2006342612 A JP2006342612 A JP 2006342612A JP 5157154 B2 JP5157154 B2 JP 5157154B2
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bicyclohexyl
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ylcarboxylic acid
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昌幸 岩窪
哲生 楠本
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DIC Corp
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本発明は、液晶材料や医薬品化合物を製造する上で有用な中間体及びその製造方法に関する。   The present invention relates to an intermediate useful for producing a liquid crystal material or a pharmaceutical compound and a method for producing the same.

シクロヘキサンジカルボン酸モノエステル誘導体は、シクロヘキサン環の両側に非対称の置換基を導入した化合物の製造中間体として有用であり、液晶化合物、医薬品等の製造に応用されている特許文献１及び２参照）。   Cyclohexanedicarboxylic acid monoester derivatives are useful as intermediates for the production of compounds in which asymmetric substituents are introduced on both sides of the cyclohexane ring, and are applied to the production of liquid crystal compounds, pharmaceuticals and the like (see Patent Documents 1 and 2).

Figure 0005157154
（式中、Ａ及びＢは任意の置換基を表す。）特に液晶化合物の製造においては、非対称の化合物が液晶化合物としての物性が優れることから有用性が高く、当該化合物に関しての応用例が開示されている（特許文献１参照）。しかしながら、シクロヘキサン骨格に替えてビシクロヘキシル骨格を有する次式
Figure 0005157154
 (In the formula, A and B represent arbitrary substituents.) In particular, in the production of liquid crystal compounds, asymmetric compounds are highly useful because of their excellent properties as liquid crystal compounds, and application examples relating to the compounds are disclosed. (See Patent Document 1). However, the following formula having a bicyclohexyl skeleton instead of the cyclohexane skeleton

Figure 0005157154
で表されるモノエステル誘導体は報告が無い。この化合物は以下の式で示すようにビシクロヘキシル骨格の４位及び４’位に異なった置換基を有する化合物を製造するために使用できる可能性を有している
Figure 0005157154
 There is no report of the monoester derivative represented by these. This compound has the potential to be used to produce compounds having different substituents at the 4 and 4 'positions of the bicyclohexyl skeleton as shown in the following formula.

Figure 0005157154
（式中、Ａ及びＢは任意の置換基を表す。）しかし、シクロヘキサン環とビシクロヘキシル骨格は構造的に見ればシクロヘキサン環が一つ多いのみであるが化学的性状においては大きな差を有する。そのため、シクロヘキサンジカルボン酸モノエステル誘導体の有する非対称化合物製造に関する知見を持って、ビシクロヘキシル骨格を有する化合物に置換したとしても同等の効果を発現する保証は無いため当該化合物の液晶材料や医薬品化合物製造への応用が遅れていた。
以上より、液晶化合物の製造中間体として有用なビシクロヘキシル骨格を有する非対称モノエステル誘導体の開発が求められていた。
Figure 0005157154
 (In the formula, A and B represent arbitrary substituents.) However, the cyclohexane ring and the bicyclohexyl skeleton have only one cyclohexane ring in terms of structure, but have a great difference in chemical properties. For this reason, we have knowledge about the production of asymmetric compounds possessed by cyclohexanedicarboxylic acid monoester derivatives, and there is no guarantee that equivalent effects will be produced even if they are replaced with compounds having a bicyclohexyl skeleton. The application of was delayed.
In view of the above, development of an asymmetric monoester derivative having a bicyclohexyl skeleton that is useful as an intermediate for producing a liquid crystal compound has been demanded.

特開平０１‐２９９２５８号公報JP-A-01-299258 国際公開２００６／１２３７２５号パンフレットInternational Publication 2006/123725 Pamphlet

本発明が解決しようとする課題は、ビシクロヘキシル骨格を有する非対称モノエステル誘導体を提供し、併せて当該化合物の効率的な製造方法を提供することにある。   The problem to be solved by the present invention is to provide an asymmetric monoester derivative having a bicyclohexyl skeleton, and to provide an efficient method for producing the compound.

本願発明者らは、上記課題を解決するために鋭意検討した結果、一般式(２)   As a result of intensive studies to solve the above problems, the present inventors have found that the general formula (2)

Figure 0005157154
(式中、Rは炭素数1〜12のアルキル基を表す。)で表されるトランス、トランス-4’-(アルコキシカルボニル)ビシクロヘキシル-4-イルカルボン酸を提供する。
Figure 0005157154
 (Wherein R represents an alkyl group having 1 to 12 carbon atoms), trans, trans-4 ′-(alkoxycarbonyl) bicyclohexyl-4-ylcarboxylic acid is provided .

本願発明のトランス、トランス-4’-(アルコキシカルボニル)ビシクロヘキシル-4-イルカルボン酸は、非対称骨格を有するビシクロヘキサン誘導体の効率的な製造に有用であり、該骨格を有する医薬品、液晶化合物の製造に好適に使用できる。   The trans, trans-4 ′-(alkoxycarbonyl) bicyclohexyl-4-ylcarboxylic acid of the present invention is useful for the efficient production of a bicyclohexane derivative having an asymmetric skeleton, and the production of pharmaceuticals and liquid crystal compounds having the skeleton. Can be suitably used.

以下に本発明について詳細に説明する。
一般式（１）及び一般式（２）においてRは炭素数1〜12のアルキル基を表すが、炭素数１〜８のアルキル基を表すことが好ましく、具体的には−CH3、−CH2CH3、−(CH2)2CH3、−(CH2)3CH3、−(CH2)4CH3、−(CH2)5CH3、−(CH2)6CH3又は−(CH2)7CH3を表すことがより好ましい。 The present invention is described in detail below.
In the general formulas (1) and (2), R represents an alkyl group having 1 to 12 carbon atoms, preferably an alkyl group having 1 to 8 carbon atoms, specifically —CH 3 , —CH 2 CH 3 ,-(CH 2 ) 2 CH 3 ,-(CH 2 ) 3 CH 3 ,-(CH 2 ) 4 CH 3 ,-(CH 2 ) 5 CH 3 ,-(CH 2 ) 6 CH 3 or- More preferably, (CH 2 ) 7 CH 3 is represented.

一般式（１）で表されるジエステルを加水分解する方法としては、アルカリ金属塩を用いてプロトン性溶媒中で反応をおこなうことが好ましい。アルカリ金属塩としては水酸化ナトリウム、水酸化カリウム、水酸化リチウムが好ましい。   As a method for hydrolyzing the diester represented by the general formula (1), it is preferable to carry out the reaction in a protic solvent using an alkali metal salt. As the alkali metal salt, sodium hydroxide, potassium hydroxide and lithium hydroxide are preferable.

用いる溶媒は、反応溶媒としては、反応を好適に進行させるものであればいずれでも構わないが、プロトン性溶媒、エーテル系溶媒もしくは極性溶媒等を好ましく用いることができる。プロトン性溶媒としては、メタノール、エタノール、イソプロピルアルコール、水等を、エーテル系溶媒としては、1,4-ジオキサン、1,3-ジオキサン、テトラヒドロフラン、ジエチルエーテル及びｔ-ブチルメチルエーテル等を、極性溶媒としてはN,N-ジメチルホルムアミド、N-メチルピロリドン、ジメチルスルホキシド及びスルホラン等を好例として挙げることができる。中でも、メタノール、エタノール等のプロトン性溶媒及びテトラヒドロフラン等のエーテル系溶媒がより好ましい。また、前記の各溶媒を単独で使用しても、2種もしくはそれ以上の溶媒を混合して使用してもよい。
一般式（２）で表される化合物の内特に好ましい化合物として次に示す化合物を挙げることができる。 The solvent used may be any reaction solvent as long as it allows the reaction to proceed suitably, but a protic solvent, an ether solvent, a polar solvent, or the like can be preferably used. As the protic solvent, methanol, ethanol, isopropyl alcohol, water, etc., and as the ether solvent, 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, t-butyl methyl ether, etc. are polar solvents. As examples, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane and the like can be mentioned as preferable examples. Among these, a protic solvent such as methanol and ethanol and an ether solvent such as tetrahydrofuran are more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.
Among the compounds represented by the general formula (2), the following compounds can be given as particularly preferred compounds.

Figure 0005157154
Figure 0005157154

以下、実施例を挙げて本発明を更に詳述するが、本発明はこれらの実施例に限定されるものではない。化合物の構造は、核磁気共鳴スペクトル(NMR)等により確認した。
（実施例） トランス、トランス-4'-(メトキシカルボニル)ビシクロヘキシル-4-イルカルボン酸の製造 EXAMPLES Hereinafter, although an Example is given and this invention is further explained in full detail, this invention is not limited to these Examples. The structure of the compound was confirmed by nuclear magnetic resonance spectrum (NMR) or the like.
(Example) Production of trans, trans-4 '-(methoxycarbonyl) bicyclohexyl-4-ylcarboxylic acid

Figure 0005157154
トランス、トランス-4', 4-ビシクロヘキシルジカルボン酸ジメチルエステル（15.8g）のメタノール（46ｍL）/テトラヒドロフラン（46ｍL）溶液に、15℃で20％水酸化ナトリウム水溶液（11.7ｍL）を滴下した。25℃で２時間攪拌した後、10％塩酸でPH=３にし、溶媒を留去して析出した固体をろ取した。固体をジクロロメタンで分散洗浄し、洗浄液を濃縮、再結晶することにより、トランス、トランス-4'-(メトキシカルボニル)ビシクロヘキシル-4-イルカルボン酸（7.35g）を無色透明の結晶（融点204-207℃）として得た。
Figure 0005157154
 A 20% aqueous sodium hydroxide solution (11.7 mL) was added dropwise at 15 ° C. to a solution of trans, trans-4 ′, 4-bicyclohexyldicarboxylic acid dimethyl ester (15.8 g) in methanol (46 mL) / tetrahydrofuran (46 mL). After stirring at 25 ° C. for 2 hours, PH = 3 with 10% hydrochloric acid, the solvent was distilled off, and the precipitated solid was collected by filtration. The solid was dispersed and washed with dichloromethane, and the washing solution was concentrated and recrystallized to obtain trans, trans-4 '-(methoxycarbonyl) bicyclohexyl-4-ylcarboxylic acid (7.35 g) as colorless and transparent crystals (melting point 204-207 ° C).

1H-NMR (400 MHz, CDCl3)
δ: 0.95 1.13 (m, 6 H), 1.33 1.45 (m, 4 H), 1.79 (bs, 4H), 2.01 (t, J = 13.6 Hz, 4 H), 2.22 (ddt, J = 3.6 Hz, 12.4 Hz, 20.8 Hz, 2 H), 3.66 (s, 3 H).
トランス、トランス-4'-(メトキシカルボニル)ビシクロヘキシル-4-イルカルボン酸は、分子内にメトキシカルボニル基とカルボキシル基の反応性の異なる二つの置換基を有する。そのため、二つの置換基の反応性の差を利用して、ビシクロヘキシル骨格の４位および４’位に異なった置換基を有する化合物を容易に製造することが可能となる。 1 H-NMR (400 MHz, CDCl 3 )
δ: 0.95 1.13 (m, 6 H), 1.33 1.45 (m, 4 H), 1.79 (bs, 4H), 2.01 (t, J = 13.6 Hz, 4 H), 2.22 (ddt, J = 3.6 Hz, 12.4 Hz, 20.8 Hz, 2 H), 3.66 (s, 3 H).
Trans, trans-4 ′-(methoxycarbonyl) bicyclohexyl-4-ylcarboxylic acid has two substituents having different reactivity between the methoxycarbonyl group and the carboxyl group in the molecule. Therefore, a compound having different substituents at the 4-position and 4′-position of the bicyclohexyl skeleton can be easily produced by utilizing the difference in reactivity between the two substituents.

Claims (2)

一般式(２)
Figure 0005157154
 (式中、Rは炭素数1〜12のアルキル基を表す。)で表されるトランス、トランス-4'-(アルコキシカルボニル)ビシクロヘキシル-4-イルカルボン酸化合物。 General formula (2)
Figure 0005157154
 (Wherein R represents an alkyl group having 1 to 12 carbon atoms), trans, trans-4 ′-(alkoxycarbonyl) bicyclohexyl-4-ylcarboxylic acid compound. Rがメチル又はエチルを表す請求項１記載の化合物。 2. A compound according to claim 1, wherein R represents methyl or ethyl.
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JP2008208119A (en) * 2007-01-31 2008-09-11 Dic Corp 4'-dialkoxymethylbicyclohexyl-4-ylmethanol and method for producing it

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JP2010533644A (en) * 2007-05-31 2010-10-28 聡美 庭山 Synthesis method of half ester
WO2019240033A1 (en) * 2018-06-11 2019-12-19 富士フイルム株式会社 Method for producing dicyclohexanedicarboxylic acid diester and method for producing dicyclohexanedicarboxylic acid
JP7062783B2 (en) * 2018-09-27 2022-05-06 富士フイルム株式会社 Method for producing dicarboxylic acid monoester

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JP2684560B2 (en) * 1988-05-26 1997-12-03 関東化学株式会社 Cyclohexanecarboxylic acid compound and liquid crystal composition containing them
JPH0344351A (en) * 1989-07-13 1991-02-26 Chisso Corp Bicyclohexane derivative liquid crystal compound

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JP2008208119A (en) * 2007-01-31 2008-09-11 Dic Corp 4'-dialkoxymethylbicyclohexyl-4-ylmethanol and method for producing it

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