JPS6330329B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel optically active polymeric substance, and more specifically, triphenyl methacrylate, which itself does not have an asymmetric carbon and exhibits no optical activity. This invention relates to a novel polymeric substance in which methyl is polymerized using an optically active initiator, and the resulting polymer exhibits large optical rotation due to its molecular asymmetry.

Conventionally, a monomer that itself does not have an asymmetric carbon and does not exhibit optical activity is polymerized using an optically active initiator, and the resulting polymer has an optical rotation that is higher than that due to the optically active group of the initiator used. It is known that there are examples showing an optical rotation of .

For example, an isotact polymer obtained by anionic polymerization of methyl methacrylate using an optically active Grignard reagent has an optical rotation that is too large, considering that it is based only on the contribution of the optically active group introduced as a terminal group. It may also indicate.
(Refer to Proceedings of the 22nd Annual Meeting of the Chemical Society of Japan (1969), p. 2111) However, polymerization of mono- or 1,1-di-substituted olefins that do not have asymmetric carbons exhibits remarkable optical activity. The polymer shown has not been obtained so far. In this case, remarkable optical activity means that it exhibits a much larger optical rotation value than the measurement error of the polarimeter or the weak optical rotation exhibited by the asymmetric initiator fragments contained in the polymer. . For example, even with the above-mentioned optically active polymethyl methacrylate, its specific optical rotation ([α] ²⁵ _D )
is about 2 in absolute value.

On the other hand, triphenylmethyl methacrylate is known to produce isotactic polymers regardless of the polymerization conditions during polymerization due to steric hindrance due to the presence of bulky substituents, and the isotactic chains are tightly formed. It is estimated that it has a helical structure. However, this polymer obtained by polymerization using a conventional initiator does not exhibit optical activity because the winding direction produces the same number of helices on the left and right sides. (J.Polym.Sci.Part B 6 , 753
(1968)) The present inventors synthesized a highly optically active polymer of triphenylmethyl methacrylate by polymerizing triphenylmethyl methacrylate using an optically active anionic initiator. This is what we have come to do.

That is, the present invention provides the general formula Mainly composed of structural units represented by
The present invention relates to a new optically active polymeric substance having the above properties and having a specific optical rotation ([α] ²⁰ _D ) of 50° or more as an absolute value.

A feature of the novel polymeric substance of the present invention is that the winding direction of the helical structure formed by the polymer is biased to either the left or right side, and therefore, it exhibits extremely large optical rotation, which is thought to be based on this. It is.

It is clear that this optical rotation depends on the helical structure of the polymer for the following reason.

(1) Although triphenylmethyl methacrylate does not have an asymmetric carbon, the polymer exhibits large optical rotation.

(2) For example, a polymer obtained by polymerizing a butyllithium-(-)-sparteine complex as an initiator has a large optical rotation even though only butyl groups are bonded as initiator fragments. To show.

(3) The polymer of (S)-1-phenylethyl methacrylate exhibits negative optical rotation, but the polymer of triphenylmethyl methacrylate obtained by polymerizing this low polymer anion as an initiator exhibits positive optical rotation. To show degree.

(4) (R)-N-(1-phenylethyl)aniline has a specific optical rotation of -19.5° for [α] ²⁵ _D , but the polymer obtained by polymerizing it with the lithium compound has [α] ²⁰ _D shows a much larger specific rotation of -70° or more.

(5) The circular dichroism spectrum of the polymer is 208 nm.
It shows a large absorption at 232 nm due to phenyl and carbonyl groups, but this absorption also exists in polymers obtained using initiators that do not contain phenyl groups, such as butyllithium-(-)sparteine complex. .

For example, when an alkali salt of an optically active compound such as lithium (R)-N-(1-phenylethyl)anilide is used as an initiator, the resulting polymer contains initiator fragments present at the starting end, such as Due to the asymmetric structure of the (R)-N-(1-phenylethyl)anilino group and the monomer unit bonded to it, the polymer molecules preferentially form a helix wound in either the left or right direction. However, on the other hand, butyllithium
When a complex such as (-)-sparteine is used as an initiator, in the polymerization reaction, the asymmetric structure of (-)-sparteine, which is present in the growing terminal of the produced polymer and is coordinated with the counter ion, is It is interpreted that this effect restricts the winding direction of the helix to either the left or right direction at the time of polymer formation, and that the helical structure is maintained even after polymerization, resulting in high optical rotation.

The novel polymeric substance of the present invention is crystalline and has a degree of polymerization of about 70 or more, and is insoluble in ordinary organic solvents.

In addition, even soluble low polymers precipitate when the solution is heated to 60°C, but when cooled, they dissolve again and are stable without decreasing their optical rotation.

The novel polymeric substance of the present invention is useful as an optical resolution agent. For example, racemic compounds such as α-substituted benzyl alcohol, α-phenylethylamine, Traeger's base, etc., and hydrocarbon compounds such as helicene, which have traditionally been difficult to optically resolve, can be prepared using the new polymeric substance of the present invention. Optical resolution can be easily and sharply performed using chromatographic methods.

Moreover, the new polymeric substance can also be used as a site for asymmetric synthesis by being present during the synthesis reaction.

Triphenylmethyl methacrylate, which is a monomer forming the structural unit of the novel optically active polymeric substance of the present invention, can be produced by a conventionally known method. That is, it is obtained by reacting silver methacrylate and triphenylmethyl chloride in ether.

(NA Adrova and LK Prokhorova,
(See Vysokomol. Soedin. 3 , 1509 (1961)) The novel polymeric substance of the present invention may contain copolymerizable monomers within a range that does not impair optical activity. The content of copolymerizable monomers is 20 mol% or less. In this case, copolymerizable monomers include styrene derivatives, conjugated dienes, methacrylic esters, methacrylonitrile, N,
Examples include N-disubstituted acrylamide. Of course, the copolymers include block copolymers,
A graft copolymer may also be used.

The polymerization method for obtaining the novel polymeric substance of the present invention is ionic polymerization.

As the polymerization initiator used for polymerization, an optically active anionic catalyst is effective.

The optically active anionic catalyst herein refers to a complex consisting of an optically active organic compound, such as an alkali metal compound or an organic alkali metal compound, and an optically active organic compound that can coordinate therewith.

Preferred examples of the above anionic catalysts include lithium (R) or (S)-N-(1-phenylethyl)anilide, and (-)-sparteine-n-
BuLi, (-)-6-ethylsparteine-n-
BuLi, (+)-6-benzylsparteine-n-
BuLi and (-)-dihydrosparteine-n-
There are complexes of (+) or (-)-sparteine or its derivatives, such as BuLi, and alkyl lithiums.

Lithium (R)-N-(1-phenylethyl)anilide was synthesized by reaction of (R)-N-(1-phenylethyl)aniline and n-BiLi. Also, its mirror image can also be used.

(-)-Sparteine-n-BuLi was prepared by mixing (-)-Sparteine and n-BuLi at room temperature.

Further examples include the following:

Examples include complexes obtained from living polymers of styrene derivatives and methacrylic acid esters and (-) or (+) sparteine and its derivatives.

Polymerization is carried out in a solvent. Any solvent may be used as long as it dissolves monomers and polymers at least in the form of low polymers, but it goes without saying that solvents that interfere with anionic polymerization and optically active polymerization cannot be used.

For example, as a polymerization initiator, (R)-N-(1-
When using (phenylethyl) anilide, benzene, toluene, tetrahydrofuran (THF), dioxane, dimethoxyethane, diethyl ether, pyridine, tetrahydropyran, dimethyl sulfoxide (DMSO), DMF, etc. can be used as the solvent.

On the other hand, when using (-)-sparteine-n-BuLi, benzene, toluene, dioxane, diethyl ether, hexane-benzene mixture, hexane-toluene mixture, etc. can be used.
THF cannot be used.

The polymerization temperature is -98° to +60°C, preferably -78° to +40°C.

Since the novel polymeric substance of the present invention undergoes living polymerization, it is preferable to cap the end with alcohol or the like after the reaction is completed.

The novel polymeric substance of the present invention is highly optically active, and its specific rotation is [α] measured in THF.
^20D _, the absolute value is 50° or more.

Since the polymeric substance of the present invention is expected to be a mixture of various degrees of polymerization, its specific optical rotation may indicate the average value of the mixture.

The specific optical rotation was measured as follows. Namely, 0.05 to 0.3 g of polymer, 10 ml of THF, 5 cm of cell,
At 20°C, measurements were made using a Yanagimoto direct-reading polarimeter (model OR-10).

The novel polymeric substance of the present invention becomes insoluble in ordinary solvents such as THF when its molecular weight becomes high.
Measuring its specific rotation becomes difficult.

In that case, for those insoluble in THF, use acid.
By partially hydrolyzing it until it dissolves in THF and measuring its specific optical rotation, it can be assumed that the specific rotation of the THF-insoluble material is larger than this. However, if it is completely hydrolyzed, the optical activity will be lost, so
It is important to stop at the point when it starts to dissolve in THF.

Furthermore, when the CD spectrum (circular dichroism) of the novel polymeric substance of the present invention is measured, it has the following properties (in THF at room temperature) as shown in FIG. 1 for Examples 1 and 2.
It shows absorption at 208 nm, 232 nm and 257-280 nm (4 lines). This CD spectrum was measured using a circular dichroism spectrometer J-40 manufactured by JASCO Corporation. The degree of polymerization is 5 or more as measured by gel permeation chromatography (GPC method).

Soluble polymers can be measured directly by GPC method, but insoluble polymers can be measured directly by GPC method.
The polymer is hydrolyzed to form polymethacrylic acid, which is further methyl esterified to convert into polymethyl methacrylate for measurement.

The optically active polymeric substance according to the present invention can be produced by optically resolving a racemate using the novel polymeric substance of the present invention. An advantage in this case is that polymeric substances with opposite optical activity can be produced.

The degree of polymerization of the novel polymeric substance of the present invention is preferably
100 or more.

Next, the present invention will be explained with reference to examples.

Example 1 0.15 g of triphenylmethyl methacrylate was placed in a sealed cell for measuring optical rotation with an optical path length of 1.0 cm.
Dissolve in 3 ml of toluene and cool to -40°C. To this, 5 mol % of n-butyllithium based on triphenylmethyl methacrylate and 1.2 times the mole of (-)-sparteine dissolved in toluene at room temperature are added.

Measure the optical rotation in a polarimeter while keeping the temperature at -40°C. The optical rotation gradually increases, and after 1.5 hours α ^-40 _D =
It reaches 2.40°.

The reaction solution was taken out and added to 30 ml of methanol to precipitate the polymer. pass through the polymer,
After washing with methanol, dry at room temperature. The polymerization degree of the obtained polymer was 42, and the specific optical rotation ([α]
²⁰ _D ) is +262°. The yield was 100%. or,
The absorption curve of the CD spectrum was as shown by the solid line in FIG.

Example 2 1.2 mmol of optically active (R)-(1-phenylethyl)-aniline ([α] ²⁵ _D = -19.5°, in methanol) was dissolved in 5 ml of toluene, and 1.0 mmol of n-butyllithium was added to the toluene. 5 ml of the solution was added and reacted at room temperature to prepare a polymerization initiator.

Meanwhile, 6.5g of triphenylmethyl methacrylate
was dissolved in 130 ml of toluene and cooled to -78°C. The above polymerization initiator was added to the solution and reacted for 3 hours under a stream of dry nitrogen.

Pour the reaction contents into methanol to precipitate the formed polymer. After washing with methanol and drying, 4.75 g of polymer was obtained.

The polymerization degree of the obtained polymer was 62, and the specific optical rotation was [α] ²⁰ _D = -70°. Moreover, its CD spectrum was as shown by the dotted line in FIG. The strength of absorption is proportional to the specific rotation.

Example 3 The polymerization reaction of Example 2 is carried out in tetrahydrofuran solvent for 2.3 hours.

The weight of the obtained polymer was 6.05 g, the degree of polymerization was 21, and the specific optical rotation was [α] ²⁰ _D = -82°.

Example 4 Triphenylmethyl methacrylate 10.0g
(30.4 mmol) was dissolved in 200 ml of toluene, and a toluene solution of n-butyllithium-(-)-sparteine (1:1.2 mol/mol) was added to the solution at -78°C with n to triphenylmethyl methacrylate. - Add butyllithium at a ratio of 1/50 (mol/mol).
The tube was sealed and reacted at -78°C. After 3 hours, 3 ml was taken out and the optical rotation was measured at -78°, and it was found to be [α] ^-78 _D = +410° in toluene. However, the polymer yield was 0.045g. Continue to react,
After standing for 24 hours, raise the temperature to -40° and react for 4 hours. Open the package and pour the contents into 2 methanol to precipitate the polymer. The polymer is taken, washed with methanol, and dried under reduced pressure. The yield of polymer is 9.85g. When this is crushed and fractionated with chloroform, 9.7 g of polymer is obtained as an insoluble portion.

The degree of polymerization of the obtained polymer was 210, and since the obtained polymer did not dissolve in THF, it was hydrolyzed in a methanol/HCl system to the extent that it could be dissolved, and the ^specific optical rotation was _measured . +50° or more, and the CD spectrum showed the same type of absorption as in Example-1.

Reference Example 1 Chloroform-insoluble portion of the pulverized triphenylmethyl methacrylate polymer obtained in Example 4: 7.35
Add g to 100 ml of hexane and leave at room temperature for 24 hours. This is filled into a glass tube with an inner diameter of 9.5 mm and a length of 37.5 cm, and 150 ml of hexane is poured into it in about 20 hours. Using this column, optical resolution is performed as follows.

Racemic Tro¨ger base () A solution of 24.5 mg dissolved in 2 ml of hexane is gradually dropped from the top, and then 10 ml of hexane is added dropwise to develop the base in the column. The hexane solution flowing out from the bottom is added dropwise at a rate of 0.19ml per minute.
Collect 3.3 ml of fraction using a fraction collector. Optical rotation for each fraction,
Measure UV and determine the concentration of the base in the solution from the UV absorption at 247 nm using a calibration curve determined in advance. Further, the specific optical rotation of the base is calculated from this concentration and the optical rotation value, and its optical purity is determined. (Optical purity 100
%, the specific optical rotation [α] ²⁵ _D is 274°. ) The amount of base collected in the 14th to 18th fractions is
At 11.82 mg, [α] ²⁵ _D is +258 to +281° (in hexane)
The optical activity purity is almost 100%.
Also, the bases collected in the 23rd to 29th flanks are
At 5.42 mg, [α] ²⁵ _D shows −258 to −278° (in hexane), and its optical purity is almost 100%.

Reference Example 2 Using the column of Reference Example 1, 160 mg of racemic 1-phenylethyl alcohol was fractionated in the same manner. The effluent was separated into 10.5 ml portions, and the fourth fraction contained [α] ²⁵ _D +23° (in CCl ₄ ), optical purity 42%.
5.4 mg of alcohol was obtained. The alcohol obtained in the 6th fraction is [α] ²⁵ _D -7.4° and the yield is
It was 49.4 mg.

Reference Column 3 Using the column of Reference Example 1, 133 mg of racemic 1-phenylethylamine was optically resolved in the same manner. Collect the effluent every 4.2 ml, and as the 7th fraction, [α] ²⁵ _D +11.8° (in hexane), 45.5 mg of amine with an optical purity of 29%, and as the 9th fraction, [α] ²⁵ _D −15°. (in hexane), 7.9 mg of amine with optical purity of 37% was obtained.

Reference Example 4 In the same manner as in Example 4, 40 g of triphenylmethyl methacrylate was dissolved in 800 ml of toluene, and a mixture was prepared from 2 mol% n-butyllithium and 1.2 times the mole of (-)-sparteine based on the monomer. Add the complex catalyst solution and polymerize at -78°C for 60 hours. After further reacting at 0° C. for 1 hour, the reaction mixture was added to methanol in step 5 with thorough stirring to precipitate the polymer. Separate the polymer, wash with methanol and dry. The dried polymer is thoroughly ground, dispersed in 700 ml of tetrahydrofuran (THF), stirred well, and centrifuged to remove the THF-insoluble portion of the polymer, washed with methanol, and dried. 38.70 g of THF-insoluble polymer are obtained. In the same manner as in Example 4, 3 ml was taken out after 10 hours during the reaction and the optical rotation was measured at -78°. In toluene, [α] ^-78 _D = +
It was 560°. However, the polymer yield was 0.125g. The degree of polymerization of the polymer obtained in this polymerization reaction was 248, and since this polymer did not dissolve in THF, it was hydrolyzed in a methanol/HCl system to the extent that it could be dissolved, and the ^optical rotation was _measured . It showed more than +50°.

Grind the polytriphenylmethyl methacrylate obtained above, and 31.7g of 200 to 250 mesh pieces.
Take out. This was dispersed in hexane, and Reference Example 1
Fill a glass tube with an inner diameter of 1.16 cm and a length of 80.6 cm in the same manner as above to prepare a column for optical separation.

Using the above column and using hexane as a solvent, 202
Optical resolution of mg of dl-menthyl benzoate was performed. As a result of development at a flow rate of 0.076 ml per minute, the amount of menthyl benzoate contained in the 19th franchise is 62.6
mg, [α] ²⁵ ₃₆₅ −129.5° (hexane), optical purity 71.1
%
It was hot. Also, 60.2mg from the 22nd to 29th fractions,
Menthyl benzoate with [α] ²⁵ ₃₆₅ +94.4° (hexane) and optical purity of 51.9% was obtained.

[Brief explanation of the drawing]

FIG. 1 is a CD spectrum diagram of the optically active substance of the present invention, where the solid line is the polymer of Example 1 and the dotted line is the polymer of Example 2.

Claims (1)

[Claims] 1. General formula Mainly composed of structural units represented by
A new optically active polymeric substance which has the above properties and has a specific optical rotation ([α] ²⁰ _D ) of 50° or more as an absolute value.