JP2010024232A - Optically active benzoate compound, and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an optically active alkoxy alcohol for the purpose of solving such a problem as the crystallization in a liquid crystal composition. <P>SOLUTION: There are provided an optically active benzoate compound, and a chiral dopant for a liquid crystal display containing the same. The optically active benzoate compound, which exhibits an excellent degree of optical rotation, has optically active characteristics equivalent to or better than those of liquid crystal chiral dopants containing a conventional optically active compound and is excellent particularly in crystallization characteristics because of increasing solubility with liquid crystal, and thus is suitable for use as a chiral dopant for a liquid crystal. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an optically active alkyl-4- (4-alkoxyphenyl-4-carbonyloxy) benzoate compound using an optically active alkoxy alcohol compound having two chiral centers that can be used in a liquid crystal composition, and production thereof. It is about the method.

  The liquid crystal display element is a display that displays characters and images by controlling the arrangement of liquid crystal molecules by voltage and adjusting the amount of light passing therethrough. At this time, the liquid crystal composition having a light amount adjusting function is composed of an optically active compound that causes a helical structure in the nematic host liquid crystal, and the helical pitch of the liquid crystal is adjusted by the twisting force of the optically active compound. The optically active compound that causes the helical structure is usually called a chiral dopant.

  The TN (twisted nematic) mode, which is currently put into practical use and frequently used, is a mode in which the pitch of the nematic liquid crystal is controlled by a chiral dopant so that the liquid crystal molecules between the upper substrate and the lower substrate are twisted by 90 °. . STN (super twisted nematic) mode is a mode in which the pitch of the nematic liquid crystal is controlled by a chiral dopant so that liquid crystal molecules between the upper substrate and the lower substrate are twisted around 220 °.

Although it is not known how many chiral dopants have been synthesized so far, S-811 having the structural formula I, CB15 having the structural formula II, and CN compounds having the structural formula III are typically known as follows. .

JP 10-195004 A JP-A-10-139706 JP-A-10-004998 Korean Special Dept. 10-061931

However, the conventional chiral dopant has a large molecular weight, and when added in a large amount to the nematic liquid crystal, there has been a problem that the performance deteriorates, such as an increase in viscosity of the liquid crystal and a tendency to cause crystallization. In order to improve this, the chiral dopant in the future should not increase the viscosity of the liquid crystal composition or cause crystallization while having a helical twisting power corresponding to the conventional chiral dopant. Therefore, it must have high chemical stability and be well dissolved in the liquid crystal composition.

In order to solve such a problem in the prior art, the present inventors focused on a primary alcohol consisting only of a carbon chain having a methyl substituent in an asymmetric carbon structure, and oxygen instead of a methylene group (CH ₂ ). Focusing on the fact that optically active alkoxy alcohols with atoms introduced can be obtained easily and inexpensively, two chiral centers with a structure in which an asymmetric carbon with a methyl group and a carbon with a hydroxy group are separated by a long chain are separated. A new optically active alkoxy alcohol having high yield and low cost was produced. In addition, a novel optically active dopant derived from a novel optically active alcohol having two chiral centers prepared was prepared. In particular, at this time, the chiral dopant has two chiral centers in the side chain, thereby preventing a problem that the chiral dopant tries to pack each other.

  Thus, the present invention minimizes the crystallization tendency of the chiral dopant in the liquid crystal composition by increasing the solubility of the liquid crystal and the chiral dopant, resulting in the chiral dopant in the liquid crystal composition containing two chiral centers. Increase stability.

  Therefore, the present invention can prevent the problem of packing between chiral dopants than conventional chiral dopants, and increase the solubility with liquid crystals in the liquid crystal composition to solve the crystallization problem due to chiral dopants. An object is to provide an alkoxy alcohol having optical activity having two chiral centers.

  Another object of the present invention is to provide a novel benzoate compound using the optically active alkoxy alcohol.

  Another object of the present invention is to provide a chiral dopant for LCD comprising the alkoxy alcohol and the benzoate compound.

（前記式で、ｍは１乃至２の整数であり、ｎは０または１の整数であり、*は非対称炭素である。） The present invention provides an optically active alkoxy alcohol compound having two chiral centers represented by the following chemical formula 1.

(In the above formula, m is an integer of 1 to 2, n is an integer of 0 or 1, and * is an asymmetric carbon.)

（前記化学式２で、Ｒ^１は以下の化学式Ａであり（ここで、ｍは１乃至２の整数であり、ｎは０または１の整数であり、*は非対称炭素である）、Ｒ^２は炭素数１乃至９の直鎖アルキル基である。）

The present invention also provides an alkyl-4- (4-alkoxyphenyl-4-carbonyloxy) benzoate compound represented by the following chemical formula 2.

(In Formula 2, R ¹ is the following chemical formula A (wherein, m is 1 or 2 an integer, n is an integer of 0 or 1, * is asymmetric carbon), R ² is (It is a linear alkyl group having 1 to 9 carbon atoms.)

（前記反応式１で、Ｒ^３は以下の化学式Ｂであり（ここで、ｍは１乃至２の整数である）、*は非対称炭素である。）

In the present invention, the production method of Chemical Formula 1 is represented by the following Reaction Formula 1.
a) A primary or secondary alcohol compound represented by the following chemical formula 4 is reacted with propylene oxide to produce a compound represented by the chemical formula 5;
b) (S, S) —compound represented by Formula 1 ((S, S) -1) and a compound represented by Formula 6 are prepared from the compound of Formula 5 using an enzyme, and c) The method includes the step of hydrolyzing the compound represented by Formula 6 to produce a compound (R, S) -1 represented by (R, S) -Chemical Formula 1.

(In the reaction formula 1, R ³ is the following chemical formula B (where m is an integer of 1 to 2), and * is an asymmetric carbon.)

  In the above, it is preferable to use a lipase novozyme as the enzyme.

In addition, the production method of Chemical Formula 1 is represented by the following Reaction Formula 2.
a) An optically active alcohol compound having one chiral center represented by Formula 8 by hydrogenation-reduction reaction after a protection reaction of the secondary alcohol compound of (S) -lactate represented by Formula 7 with benzyl bromide Manufacture and
b) reducing the compound of Formula 8 with lithium aluminum hydride to produce an optically active alcohol represented by Formula 9;
c) tosylate the optically active alcohol of Formula 9 to produce a compound of Formula 12; and d) catalytically hydrogenate the compound of Formula 12 to produce a compound of Formula 1c below. be able to.

（前記化学式１１で、Ｔｓはスルホニル基である） At this time, the compound of Formula 12 in the step c) is prepared by reacting the compound of Formula 9 with sulfonyl chloride to produce the compound of Formula 11 below, and reacting the compound of Formula 11 with 2-methyl-1-butanol. Can be produced.

(In the above chemical formula 11, Ts is a sulfonyl group)

（前記反応式３で、Ｒ^１及びＲ^２は前記化学式２で定義された通りである。） In the present invention, the production method of Chemical Formula 2 is represented by the following Reaction Formula 3,
a) reacting an optically active alkoxy alcohol compound having two chiral centers of formula 1 with a benzoxy benzoic acid of formula 13 to produce a compound represented by formula 14;
b) hydrolyzing the compound of Formula 14 to produce a compound of Formula 15; and c) reacting the compound of Formula 15 with an alkoxy benzoic acid of Formula 16.

(In Reaction Formula 3, R ¹ and R ² are as defined in Chemical Formula 2.)

（前記反応式４で、Ｒ^１及びＲ^２は前記化学式２で定義された通りである。） In addition, the production method of Chemical Formula 2 of the present invention is represented by the following Reaction Formula 4, and an optically active alkoxy alcohol compound having two chiral centers of Chemical Formula 1 is converted to an alkoxyphenylcarbonyloxybenzoic acid of Chemical Formula 17 (alkoxykphenylcarbonyl benzoic acid) Reacting may be included.

(In Reaction Scheme 4, R ¹ and R ² are as defined in Formula 2 above.)

  In addition, the present invention provides a chiral dopant including the optically active alkyl-4- (4-alkoxyphenyl-4-carbonyloxy) benzoate represented by Formula 2. In addition, the present invention can provide a liquid crystal composition for LCD containing the chiral dopant and a liquid crystal material, and a liquid crystal display device manufactured using the same.

  Hereinafter, the present invention will be described in detail. The optically active alkoxy alcohol compound represented by the chemical formula 1 of the present invention has a structure different from that of secondary alcohols described in JP-A-10-195004, JP-A-10-139706, Korean Patent Registration No. 10-061931, etc. Is different. In other words, the optically active alkoxy alcohol compound of the present invention has two asymmetric carbons to which a methyl group is bonded, that is, a chiral center, and the two asymmetric carbons and the hydroxy group of the alcohol, as shown in Chemical Formula 1. It has a secondary alcohol structure separated by a carbon chain containing oxygen. Therefore, the benzoate compound of Formula 2 prepared using such a compound can also exhibit excellent effects when used as a chiral dopant containing two chiral centers.

  In general, a chiral center can be evaluated for its superiority by evaluating its specific rotation. However, since a conventional optically active compound has one chiral center, it has a lower intrinsic light rotation than the optically active compound of the present invention having two chiral centers. In other words, the absolute value of the R contrast (R, S) is larger in two cases than in the case where the absolute value of the intrinsic photorotation is one according to the number of chiral centers, and the S contrast (S, S). It becomes bigger than the case. Therefore, when there are two chiral centers, the distinctiveness and superiority of the single chiral center are marked and superior, and the performance of the chiral dopant proportional to the intrinsic light rotation rate is even better.

  The optically active compounds of Chemical Formula 1 and Chemical Formula 2 of the present invention showing such characteristics will be specifically described.

  The optically active compound of Formula 1 of the present invention is as shown in Formula 1. Such compounds of Formula 1 are (S, S) -5-methyl-4-oxa-2-heptanol (1a), (S, S) -5-methyl-4-oxa-2-octanol (1b). Or (S, S) -6-methyl-4-oxa-2-octanol (1c).

  In addition, the method for producing an optically active alkoxy alcohol of the present invention optically resolves from a racemic secondary alcohol using an enzyme obtained in nature to produce an optically active secondary alcohol having two optically pure chiral centers. The production has the advantage that an optically active secondary alcohol having two chiral centers having a structure in which the hydroxy group of the asymmetric carbon and the alcohol is separated by a carbon chain containing oxygen can be obtained economically.

  In addition, when an enzyme is used, difficult processes such as crystal experiments such as optical resolution and optical purity are required. To remedy this problem, the present invention provides an optical resolution by synthesizing two optically pure starting materials using (S) -lactoic acid derivatives of an inexpensive and commercially available product. Has developed a synthesis method that does not require

  The production method of such an optically active alkoxy alcohol compound of the formula 1 according to the present invention is classified according to the definition of n. Hereinafter, the production method will be described separately depending on whether n is 0 or 1.

（前記反応式１−１で、Ｒ^３は以下の化学式Ｂであり、ここで、ｍは１乃至２の整数である。）

(1) When n is 0 In the chemical formula 1, m is 1 to 2, and the method for producing an optically active alkoxy alcohol compound having two chiral centers where n is 0 is represented by the reaction formula 1. More specifically, it is as shown in the following reaction formula 1-1. That is, when n is 0, the production method of Formula 1 is
a) An optically active primary or secondary alcohol compound having one chiral center represented by Chemical Formula 4 is reacted with propylene oxide to produce a mixed compound of partial isomers having two chiral centers represented by Chemical Formula 5 Manufacture and
b) The compound of the partial isomers having the two chiral centers of Formula 5 is optically resolved by an enantioselective esterification using an enzyme, and (S, S)- An optically active alkoxy alcohol compound having a chiral center ((S, S) -1) and an optically active propionate ((R, S) -6) represented by Chemical Formula 6 are produced,
c) an optical activity having two chiral centers represented by (R, S) -Chemical Formula 1, including the step of hydrolyzing a propionate having a chiral center of (R, S) in Chemical Formula 6 with NaOH. An alkoxy alcohol compound ((R, S) -1) is produced.

(In the reaction formula 1-1, R ³ is the following chemical formula B, where m is an integer of 1 to 2.)

  In the reaction formula 1-1, in step a), an optically active primary or secondary alcohol compound having one chiral center represented by the chemical formula 4 is converted into an alkoxide with NaH, and then the alkoxide is added in the presence of propylene alkoxide and a solvent. By reacting, a mixture of partial isomers of (S, S)-and (R, S)-represented by Formula 5 is produced. At this time, the secondary alcohol compound of Formula 4 can be purchased commercially, or directly manufactured and used. The specific manufacturing method is lipase novo by the method described in JP-A-10-004998. It can be produced from racemic 2-alkanol using Lime Novozyme.

  In step b), the mixture of the partial isomers of formula 5 obtained from step a) is optically resolved by a stereoselective esterification reaction with nobozyme to obtain a compound of formula 1 having a chiral center with high optical purity (S, S). The propionate compound (R, S) -6 of Formula 9 having the chiral centers of the secondary alcohol compounds (S, S) -1 and (R, S) can be produced.

  Finally, in step c), the secondary alcohol of formula 1 having a chiral center (R, S) having a high optical purity by hydrolyzing (R, S) -6 of formula 6 obtained from step b). Compound (R, S) -1 is produced.

(2) In the case where n is 1 An optically active alkoxy alcohol compound having two chiral centers in which Chemical Formula 1 is m = 1 and n is 1 can be represented by Reaction Formula 2 and more specifically. Is as shown in the following reaction formula 2-1. That is, when n is 1, the production method of Formula 1 is
a) From the alcohol of ethyl lactate represented by Chemical Formula 7, a protection reaction is performed using benzyl bromide to produce a compound represented by Chemical Formula 7,
b) reducing the compound of Formula 8 with lithium aluminum hydride to produce an optically active benzooxyalcohol compound of Formula 9;
c) reacting the compound of Formula 9 with a sulfonyl compound of 2-methyl-1-butanol of Formula 10 to produce a benzyl ether compound of Formula 12;
d) Compound (S, S) -1c represented by Chemical Formula 1, which is an optically active alcohol having two chiral centers, is obtained by dibenzylation of the compound of Chemical Formula 12 by catalytic hydrogenation reaction.

At this time, the benzyl ether compound of Formula 12 is selectively,
e) reacting the compound of Formula 9 with sulfonyl chloride to produce a sulfonyl compound of Formula 11;
f) The compound of Formula 11 can also be produced by reacting with 2-methyl-1-butanol represented by Formula 4.

  Specifically, in step a), ethyl (S) -lactate represented by Formula 7 is reacted with benzyl bromide in the presence of silver oxide to produce a compound represented by Formula 8 that protects the alcohol group. The compound of Chemical Formula 7 can be purchased and used commercially.

  In step b), the compound represented by Chemical Formula 8 is reduced with lithium aluminum hydride in the presence of a solvent to produce an optically active benzyloxy alcohol compound represented by Chemical Formula 9. At this time, an ether solvent is used as the solvent, and the reaction is carried out under reflux conditions.

  In step c), the compound represented by Formula 9 is treated with NaH to obtain an alkoxide, and then tosylated with the sulfonyl compound of (S) -2-methyl-1-butanol of Formula 10 to obtain a benzyl ether of Formula 12. A compound is produced. At this time, THF is used as the solvent, the alkoxide is reacted at a low temperature, and the reaction with the sulfonyl compound proceeds under reflux conditions.

  In step d), an optically active alcohol having two chiral centers having high optical purity is prepared by deprotection reaction (dibenzylation) of the compound represented by Formula 12 by catalytic hydrogenation. The benzyl ether compound of formula 12 can also be prepared by steps e) and f).

  In step e), a sulfonyl compound of formula 11 is prepared by reacting the compound of formula 9 with sulfonyl chloride in the presence of a solvent and a tertiary amine. At this time, a halogenated carbon such as dichloromethane or chloroform can be used as the solvent, and triethylamine or the like can be used as the tertiary amine.

  In step f), the compound represented by Formula 11 is treated with NaH to obtain an alkoxide, and then reacted with (S) -2-methyl-1-butanol represented by Formula 4 to convert the benzyl ether compound of Formula 12 To manufacture. At this time, THF is used as the solvent, the alkoxide is reacted at a low temperature, and the reaction with the sulfonyl compound proceeds under reflux conditions.

  On the other hand, the optically active alkoxy alcohol compound having two chiral centers represented by Chemical Formula 1 can be applied as a chiral dopant for liquid crystals, an intermediate for synthesizing pharmaceuticals, agricultural chemicals and natural products, and preferably applied as a chiral dopant for liquid crystals. To do.

  The benzoate compounds of the present invention have optically active characteristics similar to those of conventional liquid crystal chiral dopants. In particular, the benzoate compound of the present invention has two chiral centers, thereby preventing compact packing between the chiral dopant and the liquid crystal. It is particularly excellent in terms of crystallization characteristics by increasing the solubility.

（前記化学式２で、Ｒ^１は以下の化学式Ａであり（ここで、ｍは１乃至２の整数であり、ｎは０または１の整数であり、*は非対称炭素である）、Ｒ^２は炭素数１乃至９の直鎖アルキル基である。）

More specifically, a compound represented by the following chemical formula 2, which is a chiral dopant of liquid crystal, is produced using an optically active alkoxy alcohol having two chiral centers of the above chemical formula 1. Therefore, the present invention is characterized by providing a benzoate compound represented by the following chemical formula 2 using the compound of the chemical formula 1 as an intermediate.

(In the chemical formula 2, R ¹ is the following chemical formula A (where m is an integer of 1 to 2, n is an integer of 0 or 1, * is an asymmetric carbon), and R ² is (It is a linear alkyl group having 1 to 9 carbon atoms.)

The compound represented by Formula 2 is
(2S, 5S) -5-methyl-4-oxa-2-heptyl-4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate,
(2R, 5S) -5-methyl-4-oxa-2-heptyl-4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate,
(2S, 5S) -5-methyl-4-oxa-2-heptyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate,
(2R, 5S) -5-methyl-4-oxa-2-heptyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate,
(2S, 5S) -5-methyl-4-oxa-2-octyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate,
(2R, 5S) -5-methyl-4-oxa-2-octyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate,
(2S, 6S) -6-methyl-4-oxa-2-octyl-4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate,
(2R, 6S) -6-methyl-4-oxa-2-octyl-4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate,
(2S, 6S) -6-methyl-4-oxa-2-octyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate or (2R, 6S) -6-methyl-4-oxa-2 Preferred is -octyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate.

  The method for preparing the alkyl-4- (4-alkoxyphenyl-4-carbonyloxy) benzoate compound of Formula 2 uses the compound of Formula 1 having two chiral centers and uses the two types of Reaction Formulas 3 and 4. A preferable manufacturing method will be described below.

（前記反応式３−１で、Ｒ^１とＲ^２は化学式２で定義された通りである） First, the manufacturing method of the chemical formula 2 is as shown in the following reaction formula 3-1.
a) reacting an optically active alkoxy alcohol compound having two chiral centers of Formula 1 with 4-benzyloxybenzoic acid represented by Formula 13 to produce a 4-benzyloxybenzoate compound represented by Formula 14;
b) A 4-hydroxybenzoate compound represented by Formula 15 is prepared by reducing the compound of Formula 14 by catalytic hydrogenation reaction;
c) Optically active alkyl-4- (4-alkoxyphenyl-4-carbonyloxy) having two chiral centers of formula 2 from the compound of formula 15 by esterification reaction with 4-alkoxybenzic acid of formula 16 and DCC A benzoate compound is produced.

(The reaction formula 3-1, ^{R 1} and ^{R 2} are as defined in Formula 2)

  Specifically, in step a), an esterification reaction with 4-benzyloxybenzic acid and DCC is performed from the optically active alkoxy alcohol compound of Formula 1 in the presence of a solvent to obtain a 4-benzyloxybenzoate compound represented by Formula 14. To manufacture. At this time, a haloalkane-based or ether-based solvent such as dichloromethane can be used as the solvent.

  Next, in step b), the compound of formula 14 is reduced by a catalytic hydrogenation reaction to produce a 4-hydroxybenzoate compound represented by formula 15. At this time, a polar alcohol such as methanol is used as the solvent.

  Finally, in step c), an optically active alkyl-4- (4-alkoxyphenyl) having two chiral centers of formula 2 is obtained by proceeding esterification reaction of the compound of formula 15 with 4-alkoxybenzic acid of formula 16 and DCC. A -4-carbonyloxy) benzoate compound is produced. At this time, a haloalkane-based or ether-based solvent such as dichloromethane can be used as the solvent.

（前記反応式４−１で、Ｒ^１及びＲ^２は前記化学式２で定義された通りである。） In addition, as a second method, the production method of Chemical Formula 2 is represented by Chemical Formula 17 represented by Chemical Formula 17 from an optically active alkoxy alcohol compound having two chiral centers of Chemical Formula 1, as shown in Reaction Formula 4-1. An optically active alkyl-4- (4-alkoxyphenyl-4-carbonyloxy) benzoate compound having two chiral centers represented by Formula 2 is prepared by esterification with (4-alkoxyphenylcarbonyloxy) benzic acid and DCC.

(In Reaction Formula 4-1, R ¹ and R ² are as defined in Formula 2 above.)

  Specifically, in the presence of a solvent, from an optically active alkoxy alcohol having two chiral centers represented by Chemical Formula 1, two ester groups represented by Chemical Formula 2 can be obtained by esterification with 4- (4-alkoxyphenylcarbonyloxy) benzic acid and DCC. An optically active alkyl-4- (4-alkoxyphenyl-4-carbonyloxy) benzoate compound having a chiral center is prepared. At this time, a haloalkane-based or ether-based solvent such as dichloromethane can be used as the solvent.

  The benzoate compound of Formula 2 prepared by the method as described above contains two chiral centers in the molecule and exhibits a higher intrinsic photorotation value than before, so that the performance as a chiral dopant can be improved. .

  In addition, the optically active alkyl-4- (4-alkoxyphenyl-4-carbonyloxy) benzoate compound having two chiral centers of Formula 2 prepared in the present invention is a conventional chiral dopant for liquid crystal having an optically active alkyl group. While having a structure similar to a certain MCA (S-811), the problems of the S-811 can be improved. That is, the compound of the present invention can improve problems such as crystallization due to strong interaction between chiral dopants. Therefore, by using the benzoate derivative derived from the novel optically active alkoxy alcohol having two chiral centers of the present invention, a liquid crystal mixture having improved problems such as crystallization of chiral dopant can be produced.

  When the benzoate compound of Formula 2 is used as a chiral dopant in the present invention, it can be used in a predetermined amount.

  In addition, the chiral dopant may be included in a liquid crystal composition, and according to a preferred embodiment, the liquid crystal composition may include a chiral dopant having a predetermined composition including the chemical formula 2 and a liquid crystal material. In the liquid crystal composition, the liquid crystal material may include STN, TN, chiral nematic, and ferroelectric material. The chiral dopant compound of Formula 2 of the present invention acts as a chiral dopant in liquid crystals. The chiral dopant of Formula 2 may be included in a composition of 0.1 to 15% by weight with respect to the entire liquid crystal composition.

  In addition, the present invention can provide a liquid crystal display element using the liquid crystal composition.

  A liquid crystal display device according to an embodiment of the present invention includes a first substrate on which a thin film transistor is formed, a second substrate facing the first substrate, and a liquid crystal layer positioned between the first and second substrates. (Not shown). The liquid crystal layer can be formed by a method of coating the substrate using the liquid crystal composition. The method for manufacturing the liquid crystal display device of the present invention having the above-described structure is widely known in the field and can be sufficiently understood by those working in the field. Is omitted.

  In addition to the use as a chiral dopant as described above, the benzoate compound of Formula 2 according to the present invention can be usefully used in the field of bioactive substances and natural product synthesis as substitutes for various carbon analogs. it can.

  The optically active alkoxy alcohol of the present invention has a structure in which the asymmetric carbon and the hydroxy group of the alcohol are separated by a carbon chain containing oxygen, and is useful for the production of chiral dopants for LCDs. Can be used as Further, an optically active alkyl 4- (4-alkoxyphenyl-4-carbonyloxy) benzoate having an optically active alkoxyalkyl terminal group derived therefrom has a similar degree of photorotation as that of a conventional chiral dopant having an optically active alkyl group. Therefore, it can be usefully used as a component of a chiral dopant in the development of a liquid crystal crude product for LCD.

  Hereinafter, the present invention will be described in more detail through examples. The following examples are merely illustrative of the invention and are not intended to limit the invention.

Production Example 1
(Production of optically active 2-alkanol having two chiral centers)
An optically active 2-alkanol having two chiral centers was prepared by the following method. In order to produce optically active (S) -2-alkanol having two chiral centers, optically active (S) -2-alkanol having one chiral center is treated with NaH and reacted with propylene oxide to produce partial isomerism. (R / S, S) -2-alkanol was obtained as a mixture of the body. This partial isomer mixture produced optically active 2-alkanol having two chiral centers according to JP-A-10-004998. 0.6 equivalent of vinyl propionate is added to 2-alkanol having two chiral centers, which is a mixture of partial isomers produced, and then subjected to stereoselective esterification reaction with lipase novozyme ( R, S) -2-alkanol propionate and (S, S) -2-alkanol were obtained. Chromatography (silica gel, hexane: ether = 3: 1) was used to separate (R, S) -2-alkanol propionate from (S, S) -2-alkanol. The (R, S) -2-alkanol propionate was hydrolyzed with KOH in ethanol solvent to give (R, S) -2-alkanol. The (S, S) -isomer and (R, S) -isomer thus produced can be used for the production of the optically active alkoxy alcohol compound of the present invention. The S) -isomer was utilized.

  The optical purity of the optically active secondary alcohol having two chiral centers is obtained by reacting 2-alkanol with benzoyl chloride and the optical activity obtained by reacting the racemic benzoate with a chiral column (chiralcel OJ-H, 1% IPA- 0.05% TEA in hexane) was analyzed by HPLC, and the optical purity was 99% ee or higher.

Example 1. Synthesis of optically active 5-methyl-4-oxa-2-heptanol (1a)

1) (2R / S, 5S) -5-methyl-4-oxa-2-heptanol 5a
NaH (60% dispersion in mineral oil, 13.0 g, 0.33 mol) was washed twice with THF (50 mL), DMF (150 mL) was added, and (S)-(+)-2-butanol 4a (12 0.2 g, 0.16 mol) was slowly added at 0 ° C. After shaking at room temperature for 1 hour, a solution of propylene oxide (14.3 g, 0.25 mol) in DMF (25 mL) is gradually injected, shaken again at room temperature for about 1 hour, and then heated and refluxed at 100 ° C. for 12 hours. It was. The reaction was quenched with 1N HCl (70 mL), extracted with ether (50 mL × 3), and the organic layer was washed again with water (100 mL × 3). The organic layer was removed by simple distillation, and the residue was distilled under reduced pressure (72 ° C., 9 mmHg) (2R / S, 5S) -5 Methyl-4-oxa-2-heptanol 5a 14.0 g (65% )Obtained.

  1H-NMR δ 0.84-0.92 (m, 3H), 1.10-1.14 (m, 6H), 1.37-1.56 (m, 2H), 2.34 (brs, OH), 3.07-3.48 (m, 3H), 3.86-3.92 (m, 1H).

2) (2S, 5S) -5-Methyl-4-oxa-2-heptanol (2S, 5S) -1a and (2R, 5S) -5-methyl-4-oxa-2-heptylpropionate (6a)
(2R / S, 5S) -5-methyl-4-oxa-2-heptanol 5a (7.15 g, 54.1 mmol) to Novozyme 435 (0.11 g) and vinyl propionate (2.82 g, 28.1 mmol) ) And shaken at room temperature for 12 hours, followed by filtration. Thereafter, the organic layer is removed by simple distillation, and the residue is distilled under reduced pressure using an aspirator. {(2S, 5S) -2, 72 ° C., 9 mmHg, (2R, 5S) -3 remaining residue} , Each was purified by column chromatography (silica gel, hexane: ether = 3: 1) to give (2S, 5S) -5-methyl-4-oxa-2-heptanol (2S, 5S) -1a (2.68 g, 38%, Rf = 0.20) and (2R, 5S) -5-methyl-4-oxa-2-heptylpropionate 6a (4.30 g, 42%, Rf = 0.70).

  (2S, 5S) -1a: 1H-NMR δ 0.89 (t, 3H, J = 7.4 Hz), 1.13 (d, 3H, J = 6.0 Hz), 1.14 (d, 3H, J = 6.3 Hz) 1.39-1.58 (m, 2H), 2.98 (brs, OH), 3.23 (dd, 1H, J = 8.2, 9.3 Hz), 3.33-3 .41 (m, 2H), 3.89-3.95 (m, 1H).

  (2R, 5S) -6a: 1H-NMR δ 0.88 (t, 3H, J = 7.4 Hz), 1.10 (d, 3H, J = 6.0 Hz), 1.13 (t, 3H, J = 7.6 Hz), 1.22 (d, 3H, J = 6.3 Hz), 1.39-1.52 (m, 2H), 2.31 (q, 2H, J = 7.6 Hz), 3. 32 (sex, 1H, J = 6.1 Hz), 3.39 (dd, 1H, J = 6.0, 10.4 Hz), 3.48 (dd, 1H, J = 4.5, 10.4 Hz) , 5.02-5.05 (m, 1H).

3) (2R, 5S) -5-methyl-4-oxa-2-heptanol (2R, 5S) -1a
The (2R, 5S) -5-methyl-4-oxa-2-heptylpropionate 6a (2.70 g, 14.3 mmol) obtained above was added to a methanol (30 ml) solution with NaOH (2.80 g, 71. 7 mmol) aqueous solution (15 mL) was added and then heated and refluxed for 4 hours. The reaction was terminated by adding 6N HCl (10 mL), extracted with dichloromethane (15 mL × 3), the organic layer was collected, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure (2R, 5S) -5. -Methyl-4-oxa-2-heptanol (2R, 5S) -1a (1.61 g 85%) was obtained.

  1H-NMR δ 0.90 (t, 3H, J = 7.4 Hz), 1.12 to 1.15 (m, 6H), 1.40 to 1.61 (m, 2H), 2.84 (brs, OH) ), 3.11 (dd, 1H, J = 8.4, 9.3 Hz), 3.36 (sext, 1H, J = 6.1 Hz), 3.49 (dd, 1H, J = 3.0, 9.3 Hz), 3.89-3.95 (m, 1H).

Example 2 Synthesis of optically active 5-methyl-4-oxa-2-octanol 1b

1) (2R / S, 5S) -5-methyl-4-oxa-2-octanol 5b
In the same manner as in Example 1-1), NaH (60% dispersion in mineral oil, 2.60 g, 63.0 mmol), DMF (40 mL), (S) -2-pentanol 4b (3.70 g, 42) 0.0 mmol) solution was added propylene oxide (3.66 g, 63.0 mmol) and DMF (10 mL) solution to react to give (2R / S, 5S) -5-methyl-4-oxa-2-octanol 5b. 1.85 g (31%) was obtained.

  1H-NMR δ 0.85-0.90 (m, 3H), 1.10-1.15 (m, 6H), 1.25-1.56 (m, 4H), 2.24 (brs, OH), 3.06-3.49 (m, 3H), 3.88-3.95 (m, 1H).

2) (2S, 5S) -5-Methyl-4-oxa-2-octanol (2S, 5S) -1b and (2R, 5S) -5-methyl-4-oxa-2-octylpropionate 6b
(2R / S, 5S) -5-methyl-4-oxa-2-octanol 5b (1.85 g, 12.7 mmol) to Novozyme 435 (0.03 g) and vinyl propionate (0.76 g, 7.59 mmol) ) Was added to give (2S, 5S) -5-methyl-4-oxa-2-octanol (2S, 5S) -1b (0.53 g, 29%) and 6b (1.00 g, 39%).

  (2S, 5S) -1b: 1H-NMR δ 0.89 (t, 3H, J = 7.4 Hz), 1.13 (d, 3H, J = 6.0 Hz), 1.14 (d, 3H, J = 6.3 Hz) 1.39-1.58 (m, 2H), 2.05 (brs, OH), 3.24 (dd, 1H, J = 8.1, 9.2 Hz), 3.37 (dd 1H, J = 3.3, 9.2 Hz), 3.39-3.46 (m, 1H), 3.89-3.95 (m, 1H).

  6b: 1H-NMR δ 0.89 (t, 3H, J = 7.0 Hz), 1.10-1.16 (m, 5H), 1.22 (d, 3H, J = 6.3 Hz), 1.25 -1.52 (m, 4H), 2.31 (q, 2H, J = 7.6 Hz), 3.34-3.42 (m, 2H), 3.49 (dd, 1H, J = 4. 4, 10.4 Hz), 5.00-5.06 (m, 1H).

3) (2R, 5S) -5-methyl-4-oxa-2-octanol (2R, 5S) -1b
NaOH (10 mL) was added to a solution of (2R, 5S) -5-methyl-4-oxa-2-octylpropionate 6b (1.00 g, 4.94 mmol) in methanol (10 mL) in the same manner as in Example 1-3). An aqueous solution (8 mL) was added (0.98 g, 24.7 mmol) to obtain 0.64 g (89%) of (2R, 5S) -5-methyl-4-oxa-2-octanol (2R, 5S) -1b. .

  1H-NMR δ 0.91 (t, 3H, J = 7.2 Hz), 1.12-1.15 (m, 6H), 1.20-1.56 (m, 4H), 1.98 (brs, OH) ), 3.11 (dd, 1H, J = 8.5, 9.0 Hz), 3.40-3.53 (m, 2H), 3.88-3.95 (m, 1H).

Example 3 FIG. Synthesis of (2S, 6S) -6-methyl-4-oxa-2-octanol 1c

1) (2R / S, 6S) -6-methyl-4-oxa-2-octanol 5c
In the same manner as in Example 1-1), NaH (60% dispersion in mineral oil, 13.0 g, 0.33 mol), DMF (150 mL), (S)-(−)-2-methyl-1-butanol Propylene oxide (14.6 g, 0.25 mol) and DMF (150 mL) solution were added to the 4c (14.8 g, 0.17 mol) solution and reacted (2R / S, 6S) -6-methyl-4- 16.5 g (68%) of oxa-2-octanol 5c was obtained.

  1H-NMR δ 0.85-0.92 (m, 6H), 1.13 (d, 3H, J = 6.3 Hz), 1.11-1.67 (m, 3H), 2.32 (brs, OH) ) 3.15-3.41 (m, 4H), 3.91-3.97 (m, 1H).

2) (2S, 6S) -6-Methyl-4-oxa-2-octanol (2S, 6S) -1c and (2R, 6S) -6-methyl-4-oxa-2-octylpropionate 6c
(2R / S, 6S) -6-methyl-4-oxa-2-octanol 5c (11.7 g, 80.0 mmol) to Novozyme 435 (0.16 g) and vinyl propionate (4.16 g, 41.6 mmol) ) Were added to give (2S, 6S) -6-methyl-4-oxa-2-octanol (2S, 6S) -1c (4.82 g, 83%) and 6c (3.00 g, 40%).

  (2S, 6S) -1c: 1H-NMR δ 0.86-0.91 (m, 6H), 1.13 (d, 3H, J = 6.3 Hz), 1.11-1.66 (m, 3H) 2.12 (brs, OH), 3.19 (dd, 1H, J = 8.4, 9.5 Hz), 3.26-3.30 (m, 2H), 3.39 (dd, 1H, J = 3.2, 9.5 Hz), 3.93-3.98 (m, 1H).

  6c: 1H-NMR δ 0.85-0.90 (m, 6H), 1.13 (t, 3H, J = 7.6), 1.22 (d, 3H, J = 6.3 Hz), 1.11 −1.65 (m, 3H), 2.31 (q, 2H, J = 7.7 Hz), 3.17 (dd, 1H, J = 6.9, 9.1 Hz), 3.33 (dd, 1H, J = 6.0, 10.3 Hz), 3.37-3.48 (m, 2H), 5.05-5.10 (m, 1H).

3) (2R, 6S) -6-Methyl-4-oxa-2-octanol (2R, 6S) -1c
To a solution of (2R, 6S) -6-methyl-4-oxa-2-octylpropionate 5c (2.90 g, 14.3 mmol) in methanol (30 mL) in the same manner as in Example 1-3), NaOH was added. An aqueous solution (15 mL) (2.80 g, 71.7 mmol) was added to obtain 1.70 g (82%) of (2R, 6S) -6-methyl-4-oxa-2-octanol 11.

  1H-NMR δ 0.86-0.91 (m, 6H), 1.14 (d, 3H, J = 6.6 Hz), 1.11-1.66 (m, 3H), 3.24 (brs, OH) ) 3.16-3.42 (m, 4H), 3.93-3.96 (m, 1H).

Example 4 Synthesis of optically active (2S, 6S) -6-methyl-4-oxa-2-octanol (2S, 6S) -1c of (R, S) and (S, S) of alcohols having two conventional chiral centers The method of optically resolving a mixture of partial stereoisomers by stereoselective esterification reaction with novozyme to produce alcohol with high optical purity requires very difficult processes such as optical resolution and optical purity determination experiment. It was very difficult to obtain a high yield. To remedy this, one more chiral center with a chiral alcohol is derived from a cheap and commonly used (S) -lactic acid derivative (ie synthesized from two starting materials that are optically pure enantiomers) Optically active alcohols with two chiral centers were synthesized without having to go through an optical resolution step.

In the synthesis method, ethyl (S) -lactate (7) was reacted with benzyl bromide in the presence of 2 equivalents of silver oxide to protect the alcohol group, and then reduced with LiAlH ₄ to obtain benzyl alcohol. The obtained benzyl alcohol was treated with NaH to obtain an alkoxide, and then benzyl ether was synthesized by tosylation of (S) -2-methyl-1-butanol and reaction in a THF solvent. The obtained benzyl ether compound was subjected to catalytic hydrogenation reaction to deprotection to obtain optically active (2S, 6S) -6-methyl-4-oxa-2-octanol having two chiral centers.

A more specific method based on the reaction formula is as follows.
1) Synthesis of ethyl (S) -2- (benzyloxy) propanoate 8 Ethyl (S)-(-)-lactate (7, 12.17 g, 0.103 mol) and benzyl bromide (26.34 g, 0.154 mol) _Ag 2 O _(35.66g a mixture of), 0.154 mol) was shaken added powdered one day at 30 ° C.. Ether (100 ml) was added and filtered to remove AgBr and residual Ag ₂ O. The residue was washed with 5% aqueous KOH solution (20 ml), the organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane: ether = 5: 1). As a result, 13.41 g (63%) of Compound 8 was obtained.

  1H-NMR δ 1.30 (t, 3H, J = 7.2 Hz), 1.44 (d, 3H, J = 6.9 Hz), 4.05 (q, 1H, J = 6.9 Hz), 4.22 (Q, 2H, J = 7.2 Hz), 4.45 (d, 1H, J = 12.0 Hz), 4.70 (d, 1H, J = 12.0 Hz), 7.29-7.38 ( m, 5H).

2) Synthesis of (S) -2- (benzyloxy) propan-1-ol 9 Compound 8 (17.32 g, 0. 1 g) in a suspension of lithium aluminum hydride (4.99 g, 0.125 mol) in ether (100 ml). (0832 mol) in ether (80 ml) was added and heated and refluxed for 12 hours. The reaction was terminated with 1N dilute hydrochloric acid (250 ml), extracted with ether (60 ml × 3), the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 13.36 g (97%) of Compound 9. It was.

  1H-NMR δ 1.18 (d, 3H, J = 6.3 Hz), 1.67 (brs, OH), 3.47-3.53 (m, 1H), 3.60-3.72 (m, 2H) ), 4.49 (d, 1H, J = 11.7 Hz), 4.66 (d, 1H, J = 11.7 Hz), 7.28-7.36 (m, 5H).

3) Synthesis of benzyl ether 12 of (2S, 6S) -6-methyl-4-oxa-2-octanol (Method A)
NaH (60% dispersion in mineral oil, 1.44 g, 0.036 mol) was washed with THF (10 ml) three times, and then THF (14 ml) was added thereto to add compound 9 (5 g, 0.030 mol) in THF (20 ml). The solution was added slowly at 0 ° C. After shaking at room temperature for 30 minutes, a solution of compound 10 (8.72 g, 0.036 mol) in THF (25 ml) was gradually added at 0 ° C., shaken again at room temperature for 30 minutes, and then heated and refluxed at 100 ° C. for 12 hours. I let you. The reaction was terminated by adding 70 ml of cold distilled water, extracted with ether (30 ml × 3), and the organic layer was collected and washed with distilled water (20 ml × 3). The organic layer was dried over anhydrous sodium sulfate, and then the residue obtained by concentration under reduced pressure was purified by column chromatography (silica gel, dichloromethane) to obtain 3.94 g (56%) of Compound 12.

  1H-NMR δ 0.88 (t, 3H, J = 7.2 Hz), 0.89 (d, 3H, J = 6.6 Hz), 1.19 (d, 3H, J = 6.3 Hz), 1.08 -1.20 (m, 2H), 1.44 to 1.66 (m, 1H), 3.19-3.38 (m, 3H), 3.48-3.53 (m, 1H), 3 .70-3.72 (m, 1H), 4.62 (s, 2H), 7.27-7.35 (m, 5H).

(Method B)
Synthesis of (S) -2- (benzyloxy) propyl 4-methylbenzenesulfonate 11 Compound 9 (4.101 g, 24) was added to a solution of p-toluenesulfonyl chloride (5.68 g, 29.8 mmol) in dichloromethane (40 ml). 0.7 mmol) and triethylamine (4.96 g, 49.0 mmol) in dichloromethane (30 ml) were added, followed by shaking at room temperature for 12 hours. A saturated aqueous sodium hydrogen carbonate solution (20 ml) was added to the reaction solution to terminate the reaction, followed by extraction with dichloromethane (20 ml × 3) and washing of the organic layer with distilled water (20 ml × 3), followed by concentration under reduced pressure. The residue was purified by column chromatography (silica gel, hexane: ether = 8: 1) to obtain 7.07 g (89%) of Compound 11.

  1H-NMR δ 1.16 (d, 3H, J = 6.3 Hz), 2.43 (s, 3H), 3.73-3.78 (m, 1H), 3.96-4.00 (m, 2H ), 4.53 (d, 1H, J = 12 Hz), 4.47 (d, 1H, J = 12 Hz), 7.26-7.32 (m, 7H), 7.78 (d, 3H, J = 6.3 Hz).

Synthesis of benzyl ether 12 of (2S, 6S) -6-methyl-4-oxa-2-octanol NaH (60% dispersion in mineral oil, 1.78 g, 44.5 mmol) was washed 3 times with THF (3 ml). DMSO (17 ml) was added, and a solution of (S) -2-methyl-1-butanol (4c, 2.61 g, 29.6 mmol) in DMSO (24 ml) was gradually added. After shaking at room temperature for 30 minutes, a solution of compound 11 (9.48 g, 29.6 mmol) in DMSO (24 ml) was gradually added and shaken at room temperature for 16 hours. Cold distilled water (70 ml) was added to terminate the reaction. After extraction with ether (30 ml × 3), the organic layer was washed with distilled water (20 ml × 2) and saturated aqueous sodium chloride solution (20 ml × 2). The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane: ether = 1: 1) to obtain 5.19 g (74%) of Compound 12. .

  1H-NMR δ 0.88 (t, 3H, J = 7.2 Hz), 0.89 (d, 3H, J = 6.6 Hz), 1.19 (d, 3H, J = 6.3 Hz), 1.08 -1.20 (m, 2H), 1.44 to 1.66 (m, 1H), 3.19-3.38 (m, 3H), 3.48-3.53 (m, 1H), 3 .70-3.72 (m, 1H), 4.62 (s, 2H), 7.27-7.35 (m, 5H).

4) Synthesis of (2S, 6S) -6-methyl-4-oxa-2-octanol (2S, 6S) -1c Compound 12 (1.01 g, 4.23 mmol) in ethanol (5 ml) in catalytic amount 5 % Pd / C (20 mg) was added, and the mixture was reacted at room temperature in a hydrogenation reactor under a hydrogen stream (60 ps1) for 36 hours, filtered to remove the catalyst, and the remaining solution was dried over anhydrous sodium sulfate. Thereafter, the mixture was decompressed and concentrated to obtain 0.371 g (60%) of compound (2S, 6S) -1c.

  1H-NMR δ 0.86-0.90 (m, 3H), 0.90 (d, 3H, J = 6.3 Hz), 1.13 (d, 3H, J = 6.3 Hz), 1.11-1 .68 (m, 3H), 1.92 (brs, OH), 3.16-3.42 (m, 4H), 3.93-39 (m, 1H).

(Synthesis of chiral dopant using optically active 2-alcohol having two chiral centers)

  Embodiment 5 FIG. Synthesis of optically active dopant (2S, 5S) -5-methyl-4-oxa-2-heptyl 4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2S, 5S) -2a-C5 (Method A)

1) (2S, 5S) -5-Methyl-4-oxa-2-heptyl 4-benzyloxybenzoate (2S, 5S) -14a
To a solution of 1.2 equivalents of DCC (1.87 g, 9.07 mmol) and DMAP (1.11 g, 9.07 mmol) in dichloromethane (20 mL) was added 4-benzyloxybenzic acid 13 (1.72 g, 7.56 mmol). (2S, 5S) -5-methyl-4-oxa-2-heptanol (2S, 5S) -1a ((1.00 g, 7.56 mmol) was added and shaken for 24 hours at room temperature. The solid was filtered and removed, and the residue obtained by reducing and concentrating the surplus liquid was purified by column chromatography (silica gel, dichloromethane, Rf = 0.80) to give 4-benzyloxybenzoate (2S, 5S). Obtained 1.42 g (55%) of -14a.

  1H-NMR δ 0.89 (t, 3H, J = 7.4 Hz), 1.13 (d, 3H, J = 6.3 Hz) 1.34-1.56 (m, 5H), 3.38 (sext, 1H, J = 6.0 Hz), 3.48 (dd, 1H, J = 4.9, 10.4 Hz), 3.68 (dd, 1H, J = 5.8, 10.4 Hz), 5.12 (S, 2H), 5.20-5.25 (m, 1H), 6.98 (d, 2H, J = 9.1 Hz), 7.32-7.44 (m, 5H), 7.9 (D, 2H, J = 9.1 Hz).

2) (2S, 5S) -5-Methyl-4-oxa-2-heptyl 4-hydroxybenzoate (2S, 5S) -15a
To a solution of 4-benzyloxybenzoate (2S, 5S) -14a (1.42 g, 4.14 mmol) in methanol (15 mL), a catalytic amount of 5% Pd / C (0.30 g) was dropped, and a hydrogen stream at room temperature was added. The mixture was reacted in a hydrogenation reactor under (60 ps1) for 4 hours, diluted with dichloromethane (10 mL), filtered, the catalyst was removed, and the remaining solution was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure and concentration. 0.76 g (73%) of 4-hydroxybenzoate (2S, 5S) -15a was obtained.

  1H-NMR δ 0.89 (t, 3H, J = 7.4 Hz), 1.11 (d, 3H, J = 6.3 Hz), 1.30-1.60 (m, 5H), 1.89 (brs) OH), 3.40 (sext, 1H, J = 6.0 Hz), 3.51 (dd, 1H, J = 4.6, 10.6 Hz), 3.68 (dd, 1H, J = 5. 8, 10.6 Hz), 5.24 (sext, 1H, 6.0 Hz), 6.82 (d, 2H, J = 8.5 Hz), 7.90 (d, 2H, J = 8.5 Hz).

3) (2S, 5S) -5-Methyl-4-oxa-2-heptyl 4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2S, 5S) -2a-C5
To a solution of 1.2 equivalents of DCC (0.20 g, 0.95 mmol) and DMAP (0.12 g, 0.95 mmol) in dichloromethane (10 mL) was added 4-hydroxybenzoate (2S, 5S) -15a (0.20 g, 0 .79 mmol) and 4-pentyloxybenzic acid 16-C5 (0.17 g, 0.79 mmol) were added and shaken at room temperature for 24 hours. After completion of the reaction, the precipitated solid was filtered and removed, and the residue obtained by reducing the pressure and concentrating the residue was purified by column chromatography (silica gel, dichloromethane, Rf = 0.56) to obtain the final compound ( 0.30 g (85%) of 2S, 5S) -2a-C5 was obtained.

  1H-NMR δ 0.87-0.97 (m, 6H), 1.12 (d, 3H, J = 6.0 Hz), 1.30-1.60 (m, 9H), 1.78-1.85 (M, 2H), 3.39 (sext, 1H, J = 6.0 Hz), 3.51 (dd, 1H, J = 4.8, 10.6 Hz), 3.67 (dd, 1H, J = 5.8, 10.6 Hz), 4.05 (t, 2H, J = 6.5 Hz), 5.27 (sext, 1H, J = 6.0 Hz), 6.97 (d, 2H, J = 8) 0.8 Hz), 7.28 (d, 2H, J = 8.5 Hz), 8.11 (d, 2H, J = 8.8 Hz), 8.14 (d, 2H, J = 8.5 Hz).

(Method B)
4) (2S, 5S) -5-Methyl-4-oxa-2-heptyl 4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2S, 5S) -2a-C5
DCC (2.12 g, 10.2 mmol) and DMAP (1.26 g, 10.2 mmol), 4- (4-pentyloxyphenyl-4-carbonyloxy) benzic acid 17-C5 (2.89 g, 8.47 mmol) A solution of alcohol (2S, 5S) -1a (1.12 g, 8.47 mmol) in dichloromethane (17 ml) was added and shaken at room temperature for 48 hours. After completion of the reaction, the precipitated solid was filtered and removed, and the residue obtained by concentrating the remaining liquid under reduced pressure was purified by column chromatography (silica gel, hexane: ether = 1: 1) (2S, 5S). ) -2a-C5 2.885 g (75%).

  1H-NMR δ 0.87-0.92 (m, 6H), 1.12 (d, 3H, J = 6.0 Hz), 1.35-1.56 (m, 11H), 1.77-1.85 (M, 1H), 3.38-3.42 (m, 1H), 3.51 (dd, 1H, J = 4.8, 10.5 Hz), 3.67 (dd, 1H, J = 5. 4, 10.6 Hz), 4.05 (t, 2H, J = 6.6), 5.26-5.29 (m, 1H), 6.97 (d, 2H, J = 8.7 Hz), 7.28 (d, 2H, J = 9.9 Hz), 8.11 (d, 2H, J = 8.1 Hz), 8.13 (d, 2H, J = 8.1 Hz).

  Example 6 Synthesis of (2R, 5S) -5-methyl-4-oxa-2-heptyl 4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2R, 5S) -2a-C5

(Method A)
1) (2S, 5S) -5-Methyl-4-oxa-2-heptyl 4-benzyloxybenzoate (2R, 5S) -14a
In the same manner as in Example 5-1), DCC (1.53 g, 7.44 mmol), DMAP (0.91 g, 7.44 mmol) in dichloromethane (30 mL) solution in 4-benzyloxybenzic acid 13 (1. 41 g, 6.20 mmol) and (2R, 5S) -5-methyl-4-oxa-2-heptanol (2R, 5S) -1a (0.82 g, 6.20 mmol) were reacted to give 4-benzyloxybenzoate ( 0.94 g (45%) of 2R, 5S) -14a was obtained.

  1H-NMR δ 0.86 (t, 3H, J = 7.4 Hz), 1.12 (d, 3H, J = 6.3 Hz) 1.34 (d, 3H, J = 6.6 Hz), 1.37− 1.57 (m, 2H), 3.34-3.58 (m, 3H), 5.12 (s, 2H), 5.19-5.26 (m, 1H), 6.98 (d, 2H, J = 8.8 Hz), 7.32-7.44 (m, 5H), 7.99 (d, 2H, J = 8.8 Hz).

2) (2S, 5S) -5-Methyl-4-oxa-2-heptyl 4-hydroxybenzoate (2S, 5S) -15a
In the same manner as in Example 5-2), 4-benzyloxybenzoate (2R, 5S) -14a (0.94 g, 2.74 mmol) in methanol (15 mL) was added to a catalytic amount of 5% Pd / C ( 0.20 g) was added and hydrogenated to obtain 0.60 g (87%) of 4-hydroxybenzoate (2R, 5S) -15a.

  1H-NMR δ 0.87 (t, 3H, J = 7.4 Hz), 1.14 (d, 3H, J = 6.3 Hz), 1.34 (d, 3H, J = 6.3 Hz), 1.40 -1.62 (m, 2H), 3.40 (sext, 1H, J = 6.0 Hz), 3.54-3.63 (m, 2H), 5.21-5.27 (m, 1H) 6.82 (d, 2H, J = 8.8 Hz), 7.91 (d, 2H, J = 8.8 Hz).

3) (2R, 5S) -5-Methyl-4-oxa-2-heptyl 4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2R, 5S) -2a-C5
To a solution of DCC (0.20 g, 0.95 mmol), DMAP (0.12 g, 0.95 mmol) in dichloromethane (10 mL) was added 4-hydroxybenzoate (2R, 5S) -15a (0.20 g, 0.79 mmol) and 4 -Pentyloxybenzic acid 16-C5 (0.17 g, 0.79 mmol) was added to give 0.27 g (76%) of the final compound (2R, 5S) -2a-C5.

  1H-NMR δ 0.87 (t, 3H, J = 7.4 Hz), 0.95 (t, 3H, J = 7.0 Hz), 1.13 (d, 3H, J = 6.0 Hz), 1.25 -1.60 (m, 9H), 1.78-1.85 (m, 2H), 3.38 (sext, 1H, J = 6.0 Hz), 3.50-3.64 (m, 2H) 4.04 (t, 2H, J = 6.5 Hz), 5.27 (sext, 1H, J = 6.0 Hz), 6.97 (d, 2H, J = 9.1 Hz), 7.28 ( d, 2H, J = 8.8 Hz), 8.11 (d, 2H, J = 9.1 Hz), 8.13 (d, 2H, J = 8.8 Hz).

  Example 7 Synthesis of (2S, 5S) -5-methyl-4-oxa-2-heptyl 4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate (2S, 5S) -2a-C6

  In the same manner as in Example 5-3), 4-hydroxybenzoate (2R, 5S)-was added to a solution of DCC (0.20 g, 0.95 mmol) and DMAP (0.12 g, 0.95 mmol) in dichloromethane (10 mL). 15a (0.20 g, 0.79 mmol) and 4-hexyloxybenzic acid 16-C6 (0.18 g, 0.79 mmol) were added to give 0.27 g (76%) of the final compound (2S, 5S) -2a-C6. )Obtained.

  1H-NMR δ 0.84-0.94 (m, 6H), 1.13 (d, 3H, J = 6.0 Hz), 1.32-1.60 (m, 11H), 1.77-1.84 (M, 2H), 3.38 (sext, 1H, J = 6.0 Hz), 3.53-3.62 (m, 2H), 4.04 (t, 2H, J = 6.6 Hz), 5 .27 (sext, 1H, J = 6.0 Hz), 6.97 (d, 2H, J = 9.1 Hz), 7.28 (d, 2H, J = 8.8 Hz), 8.11 (d, 2H, J = 9.1 Hz), 8.13 (d, 2H, J = 8.8 Hz).

  13C-NMR δ 165.4, 164.4, 163.8, 154.7, 132.4, 131.2, 128.1, 121.7, 121.1, 114.4, 77.2, 70.9, 70.8, 68.4, 31.5, 29.2, 29.0, 25.6, 22.6, 19.3, 17.0, 14.0, 9.8.

  Example 8 FIG. Synthesis of (2R, 5S) -5-methyl-4-oxa-2-heptyl 4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate (2R, 5S) -2a-C6

  In the same manner as in Example 5-3), 4-hydroxybenzoate (2R, 5S)-was added to a solution of DCC (0.20 g, 0.95 mmol) and DMAP (0.12 g, 0.95 mmol) in dichloromethane (10 mL). 15a (0.20 g, 0.79 mmol) and 4-hexyloxybenzoic acid 16-C6 (0.18 g, 0.79 mmol) were added to give 0.27 g (76%) of the final compound (2R, 5S) -2a-C6. )Obtained.

  1H-NMR δ 0.84-0.94 (m, 6H), 1.13 (d, 3H, J = 6.0 Hz), 1.32-1.60 (m, 11H), 1.77-1.84 (M, 2H), 3.38 (sext, 1H, J = 6.0 Hz), 3.53-3.62 (m, 2H), 4.04 (t, 2H, J = 6.6 Hz), 5 .27 (sext, 1H, J = 6.0 Hz), 6.97 (d, 2H, J = 9.1 Hz), 7.28 (d, 2H, J = 8.8 Hz), 8.11 (d, 2H, J = 9.1 Hz), 8.13 (d, 2H, J = 8.8 Hz).

  13C-NMR δ 165.4, 164.4, 163.8, 154.7, 132.4, 131.2, 128.1, 121.7, 121.1, 114.4, 77.2, 70.9, 70.8, 68.4, 31.5, 29.2, 29.0, 25.6, 22.6, 19.3, 17.0, 14.0, 9.8.

  Example 9 Synthesis of (2S, 5S) -5-methyl-4-oxa-2-octyl 4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate (2S, 5S) -2b-C6

1) (2S, 5S) -5-Methyl-4-oxa-2-octyl 4-benzyloxybenzoate (2S, 5S) -14b
In the same manner as in Example 5-1), 4-benzyloxybenzic acid 13 (0. 0. 0) was added to a solution of DCC (0.74 g, 3.61 mmol) and DMAP (0.44 g, 3.61 mmol) in dichloromethane (10 mL). 69 g, 3.01 mmol) and (2S, 5S) -5-methyl-4-oxa-2-octanol (2S, 5S) -1b (0.44 g, 3.01 mmol) are reacted to give 4-benzyloxybenzoate ( As a result, 0.60 g (60%) of 2S, 5S) -14b was obtained.

  1H-NMR δ 0.88 (t, 3H, J = 7.0 Hz), 1.11 (d, 3H, J = 6.3 Hz), 1.20-1.57 (m, 7H), 3.41-3 .50 (m, 2H), 3.66 (dd, 1H, J = 5.6, 10.3 Hz), 5.12 (s, 2H), 5.19-5.24 (m, 1H), 6 .98 (d, 2H, J = 9.1 Hz), 7.32-1.44 (m, 5H), 7.99 (d, 2H, J = 9.1 Hz).

2) (2S, 5S) -5-Methyl-4-oxa-2-octyl 4-hydroxybenzoate (2S, 5S) -15b
In the same manner as in Example 5-2), 4-benzyloxybenzoate (2S, 5S) -14b (0.14 g, 0.416 mmol) in a methanol (10 mL) solution in a catalytic amount of 5% Pd / C ( 0.10 g) was added to cause a hydrogenation reaction to obtain 0.10 g (90%) of 4-hydroxybenzoate (2S, 5S) -15b.

  1H-NMR δ 0.88 (t, 3H, J = 7.0 Hz), 1.12 (d, 3H, J = 6.1 Hz), 1.18-1.56 (m, 7H), 3.45-3 .51 (m, 2H), 3.66 (dd, 1H, J = 5.8, 10.4 Hz), 5.24 (next, 1H, J = 6.0 Hz), 6.52 (brs, OH) 6.84 (d, 2H, J = 8.1 Hz), 7.95 (d, 2H, J = 8.2 Hz).

3) (2S, 5S) -5-Methyl-4-oxa-2-octyl 4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate (2S, 5S) -2b-C6
To a solution of DCC (0.093 g, 0.45 mmol), DMAP (0.055 g, 0.93 mmol) in dichloromethane (10 mL) was added 4-hydroxybenzoate (2S, 5S) -15b (0.10 g, 0.38 mmol) and 4 -Hexyloxybenzic acid 16-C6 (0.083 g, 0.38 mmol) was added to give 0.11 g (65%) of the final compound (2S, 5S) -2b-C6.

  1H-NMR δ 0.87-0.94 (m, 6H), 1.12 (d, 3H, J = 6.3 Hz), 1.25-1.57 (m, 13H), 1.78-1.87 (M, 2H), 3.43-3.52 (m, 2H), 3.68 (dd, 1H, J = 5.6, 10.3 Hz), 4.05 (t, 2H, J = 6. 6 Hz), 5.26 (sext, 1H, J = 6.0 Hz), 6.97 (d, 2H, J = 8.8 Hz), 7.28 (d, 2H, J = 8.5 Hz), 8. 11 (d, 2H, J = 8.5 Hz), 8.13 (d, 2H, J = 8.8 Hz).

  Example 10 Synthesis of (2R, 5S) -5-methyl-4-oxa-2-octyl 4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate (2R, 5S) -2b-C6

1) (2R, 5S) -5-Methyl-4-oxa-2-octyl 4-benzyloxybenzoate (2R, 5S) -14b
In the same manner as in Example 5-1), 4-benzyloxybenzic acid 13 (0. 0. 0) was added to a solution of DCC (0.74 g, 3.61 mmol) and DMAP (0.44 g, 3.61 mmol) in dichloromethane (10 mL). 69 g, 3.01 mmol) and (2R, 5S) -5-methyl-4-oxa-2-octanol (2R, 5S) -1b (0.44 g, 3.01 mmol) are reacted to give 4-benzyloxybenzoate ( Obtained 0.60 g (60%) of 2R, 5S) -14b.

  1H-NMR δ 0.85 (t, 3H, J = 7.0 Hz), 1.12 (d, 3H, J = 6.0 Hz), 1.21-1.55 (m, 7H), 3.41-3 .62 (m, 3H), 5.12 (s, 2H), 5.19-5.26 (m, 1H), 6.98 (d, 2H, J = 9.1 Hz), 7.32-7 .45 (m, 5H), 7.99 (d, 2H, J = 9.1 Hz).

2) (2R, 5S) -5-Methyl-4-oxa-2-octyl 4-hydroxybenzoate (2R, 5S) -15b
In the same manner as in Example 5-2), 4-benzyloxybenzoate (2R, 5S) -14b (0.14 g, 0.416 mmol) in a methanol (10 mL) solution in a catalytic amount of 5% Pd / C ( 0.10 g) was added and hydrogenated to obtain 0.10 g (90%) of 4-hydroxybenzoate (2R, 5S) -15b.

  1H-NMR δ 0.85 (t, 3H, J = 7.1 Hz), 1.13 (d, 3H, J = 6.3 Hz), 1.21-1.55 (m, 7H), 3.42-3 .61 (m, 3H), 5.21-5.25 (m, 1H), 6.83 (d, 2H, J = 8.8 Hz), 7.94 (d, 2H, J = 8.8 Hz) .

3) (2R, 5S) -5-Methyl-4-oxa-2-octyl 4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate (2R, 5S) -2b-C6
To a solution of DCC (0.093 g, 0.45 mmol), DMAP (0.055 g, 0.93 mmol) in dichloromethane (10 mL) was added 4-hydroxybenzoate (2R, 5S) -15b (0.10 g, 0.38 mmol) and 4 -Hexyloxybenzic acid 16-C6 (0.083 g, 0.38 mmol) was added to give 0.12 g (68%) of the final compound (2R, 5S) -2b-C6.

  1H-NMR δ 0.84-0.94 (m, 6H), 1.13 (d, 3H, J = 6.3 Hz), 1.25-1.53 (m, 13H), 1.78-1.87 (M, 2H), 3.40-3.67 (m, 3H), 4.05 (t, 2H, J = 6.6 Hz), 5.27 (sext, 1H, J = 6.0 Hz), 6 .97 (d, 2H, J = 8.8 Hz), 7.28 (d, 2H, J = 8.5 Hz), 8.11 (d, 2H, J = 8.5 Hz), 8.13 (d, 2H, J = 8.8 Hz).

  Example 11 Synthesis of (2S, 6S) -6-methyl-4-oxa-2-octyl- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2S, 6S) -2c-C5

1) (2S, 6S) -6-Methyl-4-oxa-2-octyl 4-benzyloxybenzoate (2S, 5S) -14b
In the same manner as in Example 5-1), DCC (1.35 g, 6.56 mmol) and DMAP (0.80 g, 6.56 mmol) in dichloromethane (25 mL) were added to 4-benzyloxybenzic acid 13 (1. 24 g, 5.47 mmol) and (2S, 6S) -6-methyl-4-oxa-2-octanol (2S, 5S) -1b (0.80 g, 5.47 mmol) were reacted to give 4-benzyloxybenzoate 1.13 g (58%) of (2S, 5S) -14b was obtained.

  1H-NMR δ 0.86 (t, 3H, J = 7.3 Hz), 0.87 (d, 3H, J = 6.9 Hz), 1.05-1.18 (m, 1H), 1.34 (d 3H, J = 6.3 Hz), 1.38-1.66 (m, 2H), 3.27-3.31 (m, 2H), 3.50 (dd, 1H, J = 4.7, 10.4 Hz), 3.61 (dd, 1H, J = 5.9, 10.4 Hz), 5.12 (s, 2H), 5.25-5.30 (m, 1H), 6.98 ( d, 2H, J = 9.1 Hz), 7.32-7.44 (m, 5H), 8.00 (d, 2H, J = 9.1 Hz).

2) (2S, 6S) -5-Methyl-4-oxa-2-octyl 4-hydroxybenzoate (2R, 5S) -15c
In the same manner as in Example 5-2), 4-benzyloxybenzoate (2S, 6S) -14c (1.13 g, 3.08 mmol) in a methanol (15 mL) solution in a catalytic amount of 5% Pd / C ( 0.30 g) was added and hydrogenated to obtain 0.81 g (98%) of 4-hydroxybenzoate (2S, 6S) -15c.

  1H-NMR δ 0.85 (t, 3HJ = 7.3 Hz), 0.86 (d, 3H, J = 6.9 Hz), 1.03-1.17 (m, 1H), 1.34 (d, 3H) , J = 6.3 Hz), 1.37-1.67 (m, 2H), 3.26-3.32 (m, 2H), 3.51 (dd, 1H, J = 4.4, 10. 7 Hz), 3.61 (dd, 1H, J = 6.0, 10.7 Hz), 5.25-5.31 (m, 1H), 6.58 (brs, OH), 6.83 (d, 2H, J = 8.8 Hz), 7.93 (d, 2H, J = 8.8 Hz).

3) (2S, 6S) -5-Methyl-4-oxa-2-octyl 4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2S, 5S) -2c-C6
To a solution of DCC (0.27 g, 1.35 mmol), DMAP (0.16 g, 1.35 mmol) in dichloromethane (10 mL) was added 4-hydroxybenzoate (2S, 6S) -15c (0.30 g, 1.13 mmol) and 4 -Pentyloxybenzic acid 16-C5 (0.25 g, 1.13 mmol) was added to give 0.45 g (88%) of the final compound (2S, 6S) -2c-C5.

  1H-NMR δ 0.84-0.96 (m, 9H), 1.06-1.74 (m, 10H), 1.78-1.87 (m, 2H), 3.29-3.32 (m 2H), 3.52 (dd, 1H, J = 4.4, 10.6 Hz), 3.62 (dd, 1H, J = 5.9, 10.6 Hz), 4.04 (t, 2H, J = 6.6 Hz), 5.32 (sext, 1H, J = 6.0 Hz), 6.97 (d, 2H, J = 8.8 Hz), 7.28 (d, 2H, J = 8.5 Hz) ), 8.11 (d, 2H, J = 8.5 Hz), 8.13 (d, 2H, J = 8.8 Hz).

  Example 12 Synthesis of (2R, 6S) -6-methyl-4-oxa-2-octyl 4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2R, 6S) -2c-C5

1) (2R, 6S) -6-Methyl-4-oxa-2-octyl 4-benzyloxybenzoate (2R, 6S) -14b
In the same manner as in Example 5-1), DCC (2.62 g, 12.7 mmol), DMAP (1.55 g, 12.7 mmol) in dichloromethane (50 mL) solution in 4-benzyloxybenzic acid 13 (2. 41 g, 10.6 mmol) and (2R, 6S) -6-methyl-4-oxa-2-octanol (2R, 6S) -1b (1.55 g, 10.6 mmol) were reacted to give 4-benzyloxybenzoate ( 2R, 6S) -14b was obtained in 3.11 g (78%).

  1H-NMR δ 0.83-0.91 (m, 6H), 1.06-1.18 (m, 1H), 1.34 (d, 3H, J = 6.6 Hz), 1.37-1.66 (M, 2H), 3.20-3.62 (m, 4H), 5.12 (s, 2H), 5.25-5.30 (m, 1H), 6.98 (d, 2H, J = 9.1 Hz), 7.34-7.45 (m, 5H), 8.00 (d, 2H, J = 9.1 Hz).

2) (2R, 5S) -5-Methyl-4-oxa-2-octyl 4-hydroxybenzoate (2R, 5S) -15b
In the same manner as in Example 5-2), 4-benzyloxybenzoate (2R, 6S) -14c (1.80 g, 4.91 mmol) in methanol (20 mL) was added to a catalytic amount of 5% Pd / C ( 0.30 g) was added and hydrogenated to give 1.27 g (98%) of 4-hydroxybenzoate (2R, 6S) -15c.

  1H-NMR δ 0.83-0.89 (m, 6H), 1.03-1.17 (m, 1H), 1.33 (d, 3H, J = 6.3 Hz), 1.36-1.67 (M, 2H), 3.21-3.65 (m, 4H), 5.26-5.32 (m, 1H), 6.82 (d, 2H, J = 8.8 Hz), 7.90 (D, 2H, J = 8.8 Hz).

3) (2R, 6S) -6-Methyl-4-oxa-2-octyl 4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate (2R, 6S) -2c-C5
4-hydroxybenzoate (2R, 6S) -15c (0.30 g, 1.13 mmol) and 4 in a solution of DCC (0.27 g, 1.35 mmol), DMAP (0.16 g, 1.35 mmol) in dichloromethane (10 mL). -Pentyloxybenzic acid 16-C5 (0.25 g, 1.13 mmol) was added to give 0.34 g (67%) of the final compound (2R, 6S) -2c-C5.

  1H-NMR δ 0.85-0.89 (m, 6H), 0.94 (t, 3H, J = 7.1 Hz), 1.07-1.64 (m, 10H), 1.78-1.87 (M, 2H), 3.21-3.65 (m, 4H), 4.04 (t, 2H, J = 6.5 Hz), 5.32 (sext, 1H, J = 6.0 Hz), 6 .97 (d, 2H, J = 8.8 Hz), 7.28 (d, 2H, J = 8.5 Hz), 8.11 (d, 2H, J = 8.5 Hz), 8.13 (d, 2H, J = 8.8 Hz).

  Example 13 Synthesis of (2S, 6S) -6-methyl-4-oxa-2-octyl 4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate (2S, 6S) -2c-C6

  In the same manner as in Example 5-3), 4-hydroxybenzoate (2S, 6S)-was added to a solution of DCC (0.27 g, 1.35 mmol) and DMAP (0.16 g, 1.35 mmol) in dichloromethane (10 mL). 15c (0.30 g, 1.13 mmol) and 4-hexyloxybenzic acid 16-C6 (0.25 g, 1.13 mmol) were added to give 0.41 g (77%) of the final compound (2S, 6S) -2c-C6. )Obtained.

  1H-NMR δ 0.84-0.94 (m, 9H), 1.06-1.74 (m, 12H), 1.78-1.87 (m, 2H), 3.29-3.32 (m 2H), 3.52 (dd, 1H, J = 4.4, 10.7 Hz), 3.62 (dd, 1H, J = 6.0, 10.7 Hz), 4.04 (t, 2H, J = 6.6 Hz), 5.32 (sext, 1H, J = 6.0 Hz), 6.97 (d, 2H, J = 9.1 Hz), 7.28 (d, 2H, J = 8.8 Hz) ), 8.11 (d, 2H, J = 8.8 Hz), 8.13 (d, 2H, J = 9.1 Hz).

  Example 14 FIG. Synthesis of (2R, 6S) -6-methyl-4-oxa-2-octyl 4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate (2R, 6S) -2c-C6

  In the same manner as in Example 5-3), 4-hydroxybenzoate (2R, 6S)-was added to a solution of DCC (0.27 g, 1.35 mmol) and DMAP (0.16 g, 1.35 mmol) in dichloromethane (10 mL). 15c (0.30 g, 1.13 mmol) and 4-hexyloxybenzic acid 16-C6 (0.25 g, 1.13 mmol) were added to give 0.43 g (81% of the final compound (2R, 6S) -2c-C6) )Obtained.

  1H-NMR δ 0.84-0.94 (m, 9H), 1.07-1.69 (m, 12H), 1.77-1.84 (m, 2H), 3.21-3.64 (m 4H), 4.04 (t, 2H, J = 6.6 Hz), 5.32 (sext, 1H, J = 6.0 Hz), 6.97 (d, 2H, J = 8.8 Hz), 7 .28 (d, 2H, J = 8.5 Hz), 8.11 (d, 2H, J = 8.5 Hz), 8.13 (d, 2H, J = 8.8 Hz).

Experimental Example 1
(Measurement comparison of light rotation)
Using a polarimeter (Autopol IV: Rudolph Research Analytical), the solvent chloroform is placed in a 10 cm cell to zero. After washing the cell with the sample solution, the average value of the values with a standard deviation of less than 5% of the values measured five times at a temperature of 20 ° C. or 26 ° C. in the cell was recorded as the intrinsic light rotation.

  At this time, the conventional compounds having one chiral center (Comparative Examples 1 to 9) and the compounds of Examples 5 to 14 described in Korean Patent Registration No. 10-0611931 were used as samples. Table 1 below shows measured values of intrinsic light rotation for the Korean Patent Registration No. 10-0611931. In addition, Table 2 below shows the intrinsic photorotation measured values for each compound of Examples 5 to 14 having two chiral centers used as chiral dopants. The optical purity of Examples 5 to 14 is the same as the optically active alcohol of the starting material.

  As can be seen from Table 1, in the case of Comparative Examples 1 to 9, when the R sequence (Configuration) is provided according to the length and structure of the carbon chain, the intrinsic light rotation rate is + 1.7 ° to + 2.8 °. In the case of having an S arrangement, the intrinsic light rotation was + 8.0 ° to + 16.1 °.

  On the other hand, as can be seen from Table 2, Examples 5 to 14, which have two chiral centers, have an (R, S) sequence depending on the length and structure of the carbon chain, from -3.799 ° to The intrinsic light rotation rate was −6.801 °, and the intrinsic light rotation rate was + 8.1 ° to + 21.797 ° when the (S, S) array was provided.

  Comparing the results depending on the number of chiral centers, the absolute value of the R contrast (R, S) is 2.2 or more in the case of two as compared with the case where the absolute value of the intrinsic light rotation is one. 2.4 times larger and 1 to 1.4 times larger in the case of S contrast (S, S). In particular, S is different from the case where the value of intrinsic light rotation is + 8.0 °, + 10.0 °, + 14.7 °, + 16.1 ° depending on the structure, and in the case of (S, S) Are + 8.1 °, + 18.203 °, + 19.103 °, + 21.799 °, etc., and all values are higher than + 18 ° except for the value of + 8.1 °.

  Therefore, when there are two chiral centers, it is judged that the performance of the chiral dopant is more excellent than that of one case, and the chiral dopant is proportional to this intrinsic light rotation rate. .

  At this time, Comparative Examples 1 to 9 are in the form of alcohol, and the compounds of Examples 5 to 14 have a benzoate structure and a difference in the skeleton. The difference above is not a big problem.

Experimental Example 2.
(Measurement of phase transition temperature)
The melting points measured by DSC observation results of chiral dopants, which are compounds having two chiral centers in Examples 5 to 14, were recorded in Table 3 below. The synthesized chiral dopant was observed with a polarizing microscope while changing the temperature at a rate of 5 ° C./min. The phase was observed by reducing the rate to 1 ° C./min near the phase transition and heating and cooling.

  For observation of the optically active alkoxy-4- (4-alkoxyphenyl-4-carbonyloxy) benzoate compound having two chiral centers in Examples 5 to 14 on the liquid crystal and measurement of the phase transition temperature, a polarizing microscope and A differential scanning analyzer (DSC) was used. The temperature of the polarizing microscope heating apparatus was corrected by using N-succinic succinimide (NBS) and benzic acid as standard samples, and the heating rate and cooling rate were adjusted to 1-2 ° C./min. The liquid crystal was put between 20 mm × 20 mm × 0.01 mm size glass plates, inserted into a heating device, and the liquid crystal was observed with a polarizing microscope. The polarizing plate and the analyzer plate were fixed at 90 °, and the magnification was 500 times. The temperature and transition energy of the differential thermal analyzer (Perkin Elmer DSC-7 series) were corrected using high purity indium (Indium; 99.9%, 156.60 ° C., 28.45 J / g). The DSC scanning range was determined based on the phase transition temperature range measured with a polarizing microscope with a heating device, and the sample amount was about 2 to 4 mg. The sample heating rate and cooling rate were adjusted to 3 ° C./min.

  As a result of measurement, most optically active alkyl 4- (4-alkoxyphenyl-4-carbonyloxy) benzoate compounds having two chiral centers derived from the optically active alkoxy alcohol of the present invention have liquid crystallinity by themselves. Not shown. Therefore, according to the present invention, the solubility of the liquid crystal and the chiral dopant can be increased in consideration of the structure of the benzoate compound. The present invention also minimizes the crystallization tendency of the chiral dopant in the liquid crystal composition, increases the stability of the chiral dopant in the liquid crystal composition containing two chiral centers, and thereby causes a phase transition of the liquid crystal composition by the chiral dopant. It can be sufficiently predicted that the decrease can be prevented.

Claims (7)

A benzoate compound represented by the following chemical formula 2.

(In the chemical formula 2, R ¹ is the following chemical formula A (where m is an integer of 1 to 2, n is an integer of 0 or 1, * is an asymmetric carbon), and R ² is (It is a linear alkyl group having 1 to 9 carbon atoms.)

The compound according to claim 1, wherein n is 0 and m is an integer of ^{1 to} 2 in the R ¹ definition of Formula 2. The compound according to claim 1, wherein n is 1 and m is an integer of 1 in the R ¹ definition of Chemical Formula 2. The compound is
(2S, 5S) -5-methyl-4-oxa-2-heptyl-4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate,
(2R, 5S) -5-methyl-4-oxa-2-heptyl-4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate,
(2S, 5S) -5-methyl-4-oxa-2-heptyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate,
(2R, 5S) -5-methyl-4-oxa-2-heptyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate,
(2S, 5S) -5-methyl-4-oxa-2-octyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate,
(2R, 5S) -5-methyl-4-oxa-2-octyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate,
(2S, 6S) -6-methyl-4-oxa-2-octyl-4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate,
(2R, 6S) -6-methyl-4-oxa-2-octyl-4- (4-pentyloxyphenyl-4-carbonyloxy) benzoate,
(2S, 6S) -6-methyl-4-oxa-2-octyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate, or (2R, 6S) -6-methyl-4-oxa- The compound of claim 1 which is 2-octyl-4- (4-hexyloxyphenyl-4-carbonyloxy) benzoate. It is shown by the following reaction formula 3,
a) reacting an optically active alkoxy alcohol compound having two chiral centers of Formula 1 with a benzoxybenzoic acid of Formula 13 to produce a compound of Formula 14;
b) hydrolysis of the compound of formula 14 to produce a compound of formula 15; and c) production of a benzoate compound of formula 2 comprising reacting the compound of formula 15 with an alkoxybenzoic acid of formula 16. Method.

(In Reaction Formula 3, R ¹ and R ² are as defined in Chemical Formula 2.) It is shown by the following reaction formula 4,
A method for producing a benzoate compound of formula 2, comprising a step of reacting an optically active alkoxy alcohol compound having two chiral centers of formula 1 with an alkoxyphenylcarbonyloxybenzoic acid of formula 17.

(Wherein in Scheme 4, R ¹ and R ² are as defined in Formula 2.) The chiral dopant containing the optically active benzoate compound of following Chemical formula 2.

(In the chemical formula 2, R ¹ is the following chemical formula A (where m is an integer of 1 to 2, n is an integer of 0 or 1, * is an asymmetric carbon), and R ² is (It is a linear alkyl group having 1 to 9 carbon atoms.)