JPS633882B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel optically active polyacrylic acid amide, and more specifically, the present invention relates to a novel optically active polyacrylic acid amide. This invention relates to a novel polyacrylic amide in which a disubstituted acrylic amide is polymerized using an optically active initiator, and the resulting polymer exhibits large optical rotation due to its molecular asymmetry.

Conventionally, N/N-disubstituted acrylamides in which both N-substituents are methyl, ethyl, propyl, butyl, isopropyl, cyclohexyl, or phenyl groups are polymerized with an anionic initiator such as ethyllithium to form a crystalline product. It is known to produce polymers (K.Butler, P.R.
Thomas and GT Tyler; J. Polymer Sci., 48,
357 (1960)).

However, there are cases where acrylamide, which itself has no asymmetric carbon and exhibits no optical activity, is polymerized using an optically active initiator, and the resulting polymer exhibits remarkable optical activity. unknown. Remarkable optical activity here means that it exhibits a clearly large optical rotation compared to the measurement error of a polarimeter or the weak optical rotation exhibited by asymmetric initiator fragments contained in the polymer.

The present inventors used an optically active anionic initiator to produce N・N-diphenylacrylamide, which itself has no optical activity, and N-phenyl-N-α-
naphthylacrylamide, N-phenyl-N-β
The present invention was achieved by synthesizing an optically active polymer by polymerizing N·N-disubstituted acrylamide such as -naphthylacrylamide.

That is, the present invention is based on the general formula However, R ₁ and R ₂ are hydrocarbon groups, at least one of which is a structural unit represented by a phenyl or naphthyl group, and the novel polyacrylic acid has a degree of polymerization of 5 or more and exhibits remarkable optical activity. It concerns amides.

A feature of the novel polyacrylic acid amide of the present invention is that the polymer maintains an asymmetric conformation (probably a helical structure in which the winding direction is biased to either the left or right side), and as a result, the polymer molecules are molecularly asymmetric. This shows the optical rotation that is thought to be based on this.

It is clear that this optical rotation depends on the conformation of the polymer, that is, on molecular asymmetry for the following reasons.

(1) Although the monomer N/N-disubstituted acrylamide has no asymmetric carbon and exhibits no optical activity, the polymer exhibits optical rotation.

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

(3) For example, the circular dichroism spectrum of N・N-diphenylacrylamide polymer is 222 nm.
It shows a large absorption at 246 nm derived from the carbonyl and phenyl groups present in the monomer units of the polymer, but this absorption is due to butyllithium-
(-)-Phenyl group like the sparteine complex,
Also present in polymers obtained using initiators that do not contain carbonyl groups.

(4) (R)-N-(1-phenylethyl)aniline has a specific optical rotation of -19.5° for [α] ²⁵ _D , but the N・N-
The polymer of diphenyl acrylamide is [α] ²⁵ _D
+7.4° (in sulfuric acid), showing a positive optical rotation opposite to that of the above aniline.

For example, if a complex such as butyllithium-(-)-sparteine is used to polymerize N.N-diphenylacrylamide, bulky substituents of the monomer and Under the influence of the asymmetric structure of (-)-sparteine, which is present at the growing end of the polymer formed and coordinated with the counter ion, the polymer grows while assuming an asymmetric structure, and even after polymerization, the asymmetric structure remains unchanged. It is interpreted that the high optical rotation of the polymer occurs as a result of the retention of the uniform structure. On the other hand, lithium (R)-N-(1-phenylethyl)
When an alkali salt of an optically active compound such as anilide is used as an initiator, the resulting polymer contains initiator fragments present at the initiation terminal, such as (R)-N-(1
-Phenylethyl)anilino group and the asymmetric structure of the monomer unit formed when bonding to this group form an asymmetric structure in the polymer molecule, which exhibits greater optical rotation than that due to the initiator fragment. considered to be a thing.

The novel polyacrylic acid amide of the present invention is crystalline, and those with a degree of polymerization of about 40 to 50 or more are soluble in concentrated sulfuric acid, but insoluble in common organic solvents. This new polyacrylic acid amide also has high heat resistance, up to 180°C in air and up to 250°C in a nitrogen atmosphere.
Even after leaving it for 6 hours, almost no weight loss was observed.
Does not melt even at 300℃.

The novel polyacrylic acid amide of the present invention is useful as an optical resolution agent. For example, racemic forms of α-substituted benzyl alcohol, α-phenylethylamine, amino acid derivatives, etc. can be optically resolved easily and sharply by chromatography using the novel polyacrylic acid amide of the present invention or metal complexes thereof. Can be done.

Furthermore, this novel polyacrylic acid amide or its metal complex can also be used as a site for asymmetric synthesis by being present during the synthesis reaction.

N·N-disubstituted acrylamide, which is a monomer forming the structural unit of the novel optically active polyacrylic acid amide of the present invention, can be produced by a conventionally known method. That is, it is obtained by reacting methacrylic acid chloride and a secondary amine in the presence of an excess of secondary amine or other tertiary amine.

Note that the novel polymeric substance mainly composed of polyacrylic acid amide of the present invention may contain a copolymerizable monomer within a range that does not impair optical activity. The content of copolymerizable monomers is 20 mol% or less. In this case, examples of copolymerizable monomers include styrene derivatives, conjugated dienes, methacrylic acid esters, methacrylonitrile, and N.N-disubstituted acrylamide. Of course, the copolymer may be a block copolymer or a graft copolymer.

The polymerization method for obtaining the novel polyacrylic acid amide 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 mentioned here is
A complex consisting of an optically active organic alkali metal compound or an organic alkali metal compound and an optically active organic compound that can coordinate therewith.

Examples include lithium (R)-N-(1-phenylethyl)anilide and a complex of butyllithium and (-)-sparteine or a derivative thereof. Lithium (R)-N-(1-phenylethyl)anilide can be synthesized by reacting (R)-N-(1-phenylethyl)aniline and butyllithium. In addition, its mirror image can also be used.

A complex of butyllithium and (-)-sparteine or a derivative thereof can be prepared by mixing butyllithium and (-)-sparteine at room temperature.

Further examples include complexes obtained from living polymers of styrene derivatives, conjugated dienes, 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 inhibit anionic polymerization and optically active polymerization cannot be used.

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

On the other hand, when using butyllithium-(-)-sparteine complex, benzene, toluene, dioxane, diethyl ether, hexane-benzene mixture, hexane-toluene mixture, THF, etc. can be used.

Polymerization temperature is -100 to 50℃, preferably -100 to 0
It is ℃.

Since the novel polyacrylic acid amide of the present invention is synthesized by living polymerization, it is preferable to cap the ends with alcohol or the like after the reaction is completed.

The polyacrylic acid amide of the present invention is expected to be a mixture of various degrees of polymerization, and its specific optical rotation may indicate the average value of the mixture.

The specific optical rotation was measured as follows. i.e. 0.1 g of polymer, 10 ml of solvent, cell optical path length 10 cm, 25
It was measured at ℃ using a polarimeter (Model DIP-181) manufactured by JASCO Corporation. Toluene or THF as solvent
However, in the case of high polymers that are insoluble in these solvents, concentrated sulfuric acid was used as the solvent. The specific optical rotation ([α] ²⁵ _D ) of a polymer dissolved in THF is 3° or more in absolute value, and the specific optical rotation ([α]
²⁵ _D ) is 0.2° or more.

Moreover, the novel polyacrylic acid amide of the present invention
When CD spectra were measured as THF solutions at room temperature, for the polymers shown in Examples 1 and 6,
Spectra as shown in Figures 1 and 2 were obtained, the former at 222nm and 246nm, and the latter at 222nm and 246nm.
Each shows strong absorption at 260 nm. This CD spectrum was measured using a circular dichroism spectrometer J-40 manufactured by JASCO Corporation.

The degree of polymerization of the novel polyacrylic acid amide of the present invention is 5 or more as measured by gel permeation chromatography (GPC method). When this is used as a racemic optical resolution agent, it is preferably 20 or more.

The novel polyacrylic acid amide metal complex of the present invention can be obtained as follows. That is, a solution of a metal compound to be formed into a complex is added to a solution of optically active polyacrylamide, and if necessary, a precipitant is added to precipitate and separate the complex. Toluene, THF, dimethylformamide, dimethyl sulfoxide, etc. can be used as a solvent for polyacrylamide. As the metal compound, chloride, inorganic salt, hydroxide, alkoxide, carbonyl compound, organic acid salt, organic compound complex, etc. are used.

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

Example 1 4.5g of N.N-diphenylacrylamide
Dissolved in 90ml of toluene and heated to -96℃ using liquid nitrogen.
Cool to Separately, 12 mmol of (-)-sparteine was dissolved in 5 ml of toluene, 5 ml of a toluene solution of 10 mmol of butyllithium was added thereto, and the mixture was reacted at room temperature to prepare a polymerization initiator. This solution
Cool 1.0 ml to -96°C and add to the monomer solution with stirring. Polymer precipitates immediately.
After reacting at -96°C for 1 hour, the reaction contents were poured into methanol, and the resulting polymer precipitate was collected, washed with methanol, and dried. 4.2 g of polymer (93% yield) was obtained. Polymer is
THF soluble, degree of polymerization is 23, specific optical rotation [α]
^25D was _−47.2 ° (in THF). Moreover, its CD spectrum was as shown in FIG.

Example 2 4.5g of N.N-diphenylacrylamide
Dissolve in 90 ml of toluene and cool to -78°C. To this was added 1.0% of the polymerization initiator solution of Example 1 cooled to -78°C.
ml with stirring and react at -78°C for 1 hour. The reaction mixture was treated in the same manner as in Example 1 to obtain 4.14 g of polymer (92% yield). Polymer is
THF soluble, degree of polymerization is 25, specific optical rotation [α]
^25D was -31.8 _° (in THF).

Example 3 4.5g of N.N-diphenylacrylamide
Dissolve in 45 ml of toluene and cool to -78°C. On the other hand, a polymerization initiator is prepared by reacting 10 mmol of butyllithium and 12 mmol of (+)-6-benzylsparteine in 10 ml of toluene at room temperature. 0.33 ml of this solution is cooled to -78°C and added to the above monomer solution with stirring. After reacting at −78° C. for 1 hour, the reaction solution is treated in the same manner as in Example 1 to obtain 42.3 g of polymer (yield: 94%). This polymer partially contained a high polymer insoluble in THF, and the amount thereof was 0.6 g.
The part soluble in THF has a degree of polymerization of 35 and a specific optical rotation [α]
²⁵ _D was -37.8°. The [α] ²⁵ _D of the THF-insoluble portion was −13° (in concentrated sulfuric acid).

Example 4 3 g of N.N-diphenylacrylamide was added to 30
Dissolve in ml of toluene and cool to -78°C. on the other hand
10 mmol of butyllithium and 12 mmol of (R)-N-(1-phenylethyl)aniline in 10
ml of toluene to prepare a polymerization initiator. Take 0.14 ml of this solution, add it to the monomer solution with stirring, and react at -78°C for 30 minutes.
2.82 g of polymer (yield 94
%)was gotten. The polymer was almost insoluble in THF, and its [α] ²⁵ _D was +7.4° (in concentrated sulfuric acid).

Example 5 5.5 g of N-phenyl-N-α-naphthylacrylamide is dissolved in 90 ml of toluene and cooled to -78°C. 1.0 ml of the toluene solution of the butyllithium-(-)-sparteine complex shown in Example 1 is cooled to -78 DEG C. and added to the monomer solution with stirring. After reacting at -78°C for 1 hour, the reaction solution was treated in the same manner as in Example 1, resulting in 3.52 g of polymer (yield:
64%). Polymer is toluene, THF
The degree of polymerization was 24, and the specific optical rotation [α] ²⁵ _D was +8.7° (in toluene).

Example 6 5.5 g of N-phenyl-N-β-naphthylacrylamide is dissolved in 100 ml of toluene and cooled to -78°C. 1.0 ml of the initiator solution shown in Example 1 was added to -78
Cool to 0.degree. C. and add to the monomer solution with stirring. After reacting for 10 minutes, the reaction solution is treated in the same manner as in Example 1 to obtain 5.01 g of polymer (yield 91%). The polymer is soluble in toluene, THF,
Its degree of polymerization was 35, and its specific optical rotation [α] ²⁵ _D was +81.7° (in toluene). Also, the CD spectrum is the second
It was as shown in the figure.

Example 7 Polymerization of N-phenyl-N-β-naphthylacrylamide was carried out at a polymerization temperature of 0° C., and the other conditions were as in Example 6.
I did the same thing for 60 minutes. 5.19 g of polymer (yield 94.3%) was obtained. 2.9g in the polymer
It was soluble in THF and the rest was insoluble. The degree of polymerization of the soluble portion was 30, and its specific optical rotation [α] ²⁵ _D was −32.1° (in THF).

Example 8 0.5 g of the N·N-diphenylacrylamide polymer shown in Example 1 was dissolved in 10 ml of toluene,
0.5 g of titanium tetrachloride dissolved in 5 ml of toluene
Gradually add the solution dropwise while stirring at room temperature. A complex of polymer and titanium tetrachloride precipitates. Pour the reaction solution into a large amount of hexane and centrifuge the precipitate. After washing with hexane and drying, 0.96 g of powder is obtained.

[Brief explanation of the drawing]

Figure 1 shows the polymer of the present invention obtained in Example 1.
CD Spectrum FIG. 2 is the CD spectrum of the polymer of the present invention obtained in Example 6.

Claims (1)

[Claims] 1. General formula (However, R ₁ and R ₂ are hydrocarbon groups, at least one of which is a phenyl group or a naphthyl group), and the degree of polymerization is 5 or more,
An optically active polymer that also exhibits optical rotation.