JPS6236011B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing an optically active halogen compound, and more specifically,
general formula (At least one of R ₁ to _{R 4} in the formula is an alkyl, alkenyl, alkynyl, aralkyl, aryl, alkoxy, aryloxy group, etc., and the others contain hydrogen, and the compound of the formula is stably present, and It is any organic residue that does not hinder the addition of halogen to a carbon-carbon unsaturated bond, and is a group that can be interconnected to form a ring.

However, R ₁ and R ₂ and R ₃ and R ₄ must not be the same residue at the same time. The present invention also relates to a novel method for producing an optically active halogenated hydrocarbon represented by the following formula: if X ₁ is hydrogen, then X ₂ is a halogen, and if X ₂ is hydrogen, then X ₁ is a halogen.

Attempts to synthesize optically active halides from compounds with carbon-carbon double bonds were made by Penzien and Schmidt [K. Penzien, GM Schmidt;
Angew Chem.Int.Ed.Engl., 8 608 (1969)]
was first carried out by , who not only used optically active starting materials, but also achieved this using larger single crystals. Therefore, this method is extremely limited in that it cannot be applied to optically active compounds that cannot be formed into single crystals or to compounds that are not optically active, and cannot be applied to general compounds with double bonds. isn't it.

If optically active halides, which are effective as intermediates or starting materials for useful compounds such as agricultural chemicals, pharmaceuticals, and amino acids, could be synthesized from compounds with ordinary unsaturated bonds, the synthesis method would be extremely useful.

As a result of various studies for this purpose, the present inventors discovered that after clathrating ethylenically unsaturated compounds with carbon-carbon double bonds into cyclodextrins, gaseous hydrogen halide was added to these solid clathrate compounds. They succeeded in synthesizing optically active halogenated hydrocarbons by reacting the halogenated hydrocarbons with the clathrates and then recovering the halogenated hydrides from the clathrates.

The cyclodextrin used in the present invention is
It is a cyclic dextrin obtained by the action of special microorganisms or enzymes on starch or dextrin, and its characteristic feature is that it has a donut-shaped molecular structure and a cavity with a diameter of about 6 to 10 Å inside. Three types of cyclodextrin are currently isolated, α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin, depending on the number of constituent units of d-glucose. Any of these may be used, or a mixture thereof may be used. In addition, modified cyclodextrins with suitable chemical groups introduced into the side chains of these cyclodextrins and polycyclodextrins in which cyclodextrins are insolubilized do not hinder inclusion, and
It can be used as long as it does not interfere with the addition of hydrogen halide to the inclusion compound. That is, it is known that cyclodextrin forms clathrates with various substances, such as hydrocarbons, as a characteristic of its doughnut-shaped molecular structure composed of glucose.

The compound containing at least one carbon-carbon double bond in the molecule used as a raw material in the present invention has the general formula (At least one of R ₁ to _{R 4} in the formula is an alkyl, alkenyl, alkynyl, aralkyl, aryl, alkoxy, aryloxy group, etc., and the others contain hydrogen. without hindering the inclusion of
Furthermore, it is any organic residue that does not prevent the addition of halogen to a carbon-carbon unsaturated bond, and is a group that can be interconnected to form a ring. Examples of these organic residues include nitro groups, cyano groups, halogens, carboxyl groups, carbonyl groups, hydroxyl groups, alkoxy groups, and the above-mentioned alkyl, allyl, aryl, alkynyl, ararykyl, and alkenyl groups substituted with these groups. . Also, R ₁ and R ₂
and R ₃ and R ₄ must not be the same residue at the same time).

For example, crotonic acid (2-butenoic acid), 2-pentenoic acid, 3-octenoic acid, acrylic acid, methacrylic acid, tiglic acid,
Aliphatic hydrocarbon acids such as angelic acid, oleic acid, elaidic acid, linoleic acid, cinnamic acid,
- and m-, p-methylcinnamic acid, cinnamylideneacetic acid, o- and m-, p-hydroxycinnamic acid, and other aromatic hydrocarbons and their alkyl, alkenyl, alkynyl, aralyl, and aryl esters.

Furthermore, ethylene, propylene, butene, isobutene, pentene, hexene, heptene, octene, 2-methylbutene-1,3-methylbutene-
1. Aliphatic unsaturated hydrocarbons such as trimethylethylene and styrene, α- and β-methylstyrene o- and m-, p-methylstyrene, allylbenzene, 1-phenyl-2-butene, tetraphenylethylene, allyl naphthalene, 1,1-
There are aromatic substituted unsaturated hydrocarbons such as diphenylethylene and vinylnaphthalene. Halogens such as vinyl fluoride, vinyl bromide, allyl chloride, anyl bromide, allyl iodo, trichloroethylene, 1,2-dichloroethylene, 1-phenyl-3-bromo-propene-1, o- and m-, p-chlorostyrene These include substituted unsaturated hydrocarbons, unsaturated hydroxy compounds such as allyl alcohol, cinnamic alcohol, and crotyl alcohol, and unsaturated aldehydes such as crotonaldehyde and cinnamic aldehyde.

There are various methods for inclusion, including a kneading method and a solution method.

In the kneading method, water (approximately 0.1 to 6 times the weight of cyclodextrin) is added to cyclodextrin to form a paste. Next, the unsaturated compound to be included is added and thoroughly kneaded. The kneading time is approximately 1 to 12 hours, preferably 2 to 8 hours, and the kneading temperature may be arbitrary, but room temperature is sufficient. A crusher, ball mill, disper mill, emulsifier, etc. are sufficient for kneading. on the other hand,
In the solution method, a saturated aqueous solution of cyclodextrin is prepared, an unsaturated compound is added thereto, and the mixture is stirred for 30 minutes to 12 hours, preferably 1 to 4 hours, to obtain the clathrate compound as a precipitate.

The obtained clathrate compound can be dried by various methods, including spray drying and vacuum drying.
The odor inherent to each unsaturated compound in the resulting powder has disappeared, but when it is poured into hot water or treated with diethyl ether, it re-emits the odor of the clathrate before it is clathrated. When H nuclear magnetic resonance is measured after dissolving it in a dissolving solvent, a signal derived from the clathrate compound is observed.
It is clear that the powder contains unsaturated compounds.

Hydrogen halide gas is blown into the clathrate compound of the unsaturated compound thus obtained in the unpowdered state while blocking light, and the mixture is heated at -50°C to 90°C, preferably at -20°C.
~50℃, 15 minutes to 150 hours, preferably 30 minutes to 100 hours
Allow time to react. The reaction temperature and time are determined appropriately depending on the stability of the clathrate, the reactivity of the unsaturated compound included, the reactivity of the hydrogen halide to be added, and the stability of the hydrogen halide produced. You should choose. After the reaction, excess unreacted hydrogen halide gas is removed under vacuum, followed by extraction with a suitable solvent such as diethyl ether to obtain the desired optically active hydrogen halide from the clathrate.

The hydrogen halide gas used in the present invention may be any of hydrogen fluoride, hydrogen chloride, hydrogen bromide, and hydrogen iodide gas.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 200 g of α-cyclodextrin is placed in 1600 ml of water and heated to about 80° C. while stirring. After adding 20 g of crotonic acid to the obtained solution and stirring while heating at 50° C. for about 3 hours, the mixture was allowed to cool and the resulting precipitate was filtered to obtain a clathrate compound. This clathrate compound was vacuum dried at 20° C. overnight, placed in a sealed container, and exposed to hydrogen chloride gas at room temperature for 100 hours without exposure to light, and then unreacted hydrogen chloride gas was removed under vacuum. Hydrochloride was extracted with ethyl ether and chromatographed using a silica gel column and 1,2-dichloroethane.
-Chlorobutanoic acid was obtained. [α] ²⁵ _D measured at a yield of 50% and a concentration of 0.5 g/100 ml in dichloromethane is -
It was 1.8.

Elemental analysis value (as C ₄ H ₇ O ₂ Cl) Calculated value C = 39.20% H = 5.72% Cl = 28.95% Analysis value C = 39.13% H = 5.70% Cl = 29.00% Example 2 150 g of β-cyclodextrin Add 15 g of methacrylic acid to a solution obtained by heating to about 60°C while stirring in 1000ml of water, and keep at 40°C for about 2 hours.
After stirring while heating, the mixture was allowed to cool. After filtering the resulting precipitate, it was vacuum dried for 24 hours to obtain a clathrate compound. This clathrate compound was placed in a sealed container and exposed to hydrogen chloride gas at 30°C for 60 hours without exposing it to light.
The same treatment as in Example 1 was carried out to obtain 2-chloro-2-methylpropanoic acid. The yield was 67%, and the [α] ²⁵ _D measured at a concentration of 0.6 g/100 ml in dichloroethane was -1.5.

Elemental analysis value (as C ₄ H ₇ O ₂ Cl) Calculated value C = 39.20% H = 5.72% Cl = 28.95% Analysis value C = 39.33% H = 5.69% Cl = 28.87% Example 3 Same as Example 1 The α-cyclodextrin clathrate compound of styrene obtained was exposed to hydrogen bromide gas at -20°C for 90 hours, and then treated in the same manner as in Example 1 to obtain 1-bromo-1-phenylethane. Yield 19%, [α] ²⁵ _D in trichloromethane is +1.2
It was hot.

Elemental analysis value (as C ₈ H ₉ Br) Calculated value C = 51.92% H = 4.87% Br = 43.21% Analysis value C = 51.84% H = 4.90% Br = 43.30% Example 4 Obtained in the same manner as Example 2 The β-cyclodextrin clathrate of trans-cinnamic acid was prepared at 20°C.
After being exposed to hydrogen bromide gas for 45 hours, it was treated in the same manner as in Example 2 to obtain 2-bromo-3-phenylpropanoic acid. Yield 42%, concentration in ethanol 0.45
[α] ²⁵ _D measured in g/100ml was +2.2.

Elemental analysis value (as C ₉ H ₉ O ₂ Br) Calculated value C = 47.18% H = 3.93% Br = 34.91% Analysis value C = 47.23% H = 3.89% Br = 34.97% Example 5 Already proposed method [Wiedenhof et al., Die
Starke, 21, 119 (1969)] γ-cyclodextrin polymer (average molecular weight 5500) 100
300 g of water was added to the mixture and thoroughly stirred and mixed to form a paste. 10 g of β-methylstyrene was added thereto, and the mixture was sufficiently stirred and mixed to obtain a poly(γ-cyclodextrin) clathrate of β-methylstyrene. This clathrate compound was heated at 10℃ for 72 hours.
After exposure to hydrogen bromide gas, the same treatment as in Example 1 was performed to obtain 1-bromo-1-phenylpropane in a yield of 46%. Concentration in dichloromethane: 0.6g/100
[α] ²⁵ _D measured in ml was -1.7.

Elemental analysis value (as C ₉ H ₁₁ Br) Calculated value C = 54.30% H = 5.53% Br = 40.17% Analysis value C = 54.96% H = 5.49% Br = 39.72% Example 6 Using the same method as Example 5 Poly(β-cyclodextrin) of allylbenzene was prepared in the same manner as in Example 5 using the produced β-cyclodextrin polymer (average molecular weight 5000) and allylbenzene.
A clathrate compound was obtained. This clathrate compound was exposed to hydrogen iodide gas at 5° C. for 80 hours, and then treated in the same manner as in Example 1 to obtain 2-iodo-3-phenylpropane in a yield of 58%. Concentration in dichloromethane 0.47
[α] ²⁵ _D measured at g/100ml was -3.0.

Elemental analysis value (as C ₉ H ₁₁ I) Calculated value C = 43.92% H = 4.47% I = 51.61% Analysis value C = 44.16% H = 4.40% I = 51.47% Example 7 Obtained in the same manner as Example 2 β of cinnamic nitrile
-The cyclodextrin clathrate compound was exposed to hydrogen chloride gas at 25° C. for 20 hours, and then treated in the same manner as in Example 1 to obtain 1-chloro-1-cyano-2-phenylethane. The yield was 80%, and the [α] ²⁵ _D in dichloromethane was +16.

Elemental analysis value (as C ₉ H ₈ NCl) Calculated value C = 65.28% H = 4.84% N = 8.46% Cl = 21.43% Analysis value C = 65.02% H = 4.88% N = 8.40% Cl = 21.50% Example 8 α of ethyl cinnamate obtained in the same manner as in Example 1
-The cyclodextrin clathrate compound was exposed to hydrogen bromide gas at 20°C for 20 hours, and then treated in the same manner as in Example 1 to obtain ethyl 2-bromo-3-phenylpropanoate. The yield was 17%, and the [α] ²⁵ _D in dichloromethane was +8.8.

Elemental analysis value (as C ₁₁ H ₁₃ O ₂ Br) Calculated value C = 51.38% H = 5.06% Br = 31.10% Analysis value C = 51.43% H = 5.09% Br = 31.00% Example 9 Using γ-cyclodextrin In the same manner as in Example 2, a γ-cyclodextrin clathrate of benzyl cinnamate was obtained. This clathrate compound is −
After being exposed to hydrogen fluoride gas at 5°C for 30 hours, the mixture was treated in the same manner as in Example 1 to obtain benzyl 2-fluoro-3-phenylpropanoate. The yield was 35%, and the [α] ²⁵ _D in trichloromethane was -2.4.

Elemental analysis value (as C ₁₆ H ₁₅ O ₂ F) Calculated value C = 74.42% H = 5.81% F = 7.36% Analysis value C = 74.50% H = 5.78% F = 7.41% Example 10 Same as Example 2 β of ethyl cinnamate obtained by
-The cyclodextrin clathrate compound was exposed to hydrogen bromide gas at 0°C for 35 hours, and then treated in the same manner as in Example 1 to obtain ethyl 2-bromo-3-phenylpropanoate. The yield was 21%, and the [α] ²⁵ _D in dichloromethane was -6.1.

Elemental analysis value (as C ₁₁ H ₁₃ O ₂ Br) Calculated value C = 51.38% H = 5.06% Br = 31.10% Analysis value C = 51.31% H = 5.02% Br = 31.20% In order to characterize the present invention, A comparative example is shown below.

Comparative Example 1 The β-cyclodextrin clathrate of ethyl cinnamate used in Example 10 was dissolved in dimethyl sulfoxide and mixed with a glacial acetic acid solution of hydrogen bromide at 0°C. Thereafter, the same treatment as in Example 10 was carried out to obtain ethyl 2-bromo-3-phenylpropanoate.
Compared to Example 10, the yield was low at 9%, and [α] ²⁵ _D was also small at -1.6.

Comparative Example 2 Separately obtained racemic 1-bromo-1-phenylethane was prepared by the method of Cramer et al. [F. Cramer, W.
Dietsch; Chem. Ber., 92 378 (1959)] using α-cyclodextrin. In this case, [α] ²⁵ _D is −0.8, which is the opposite numbering, and the optical yield is also lower than that of Example 3.

Therefore, it is clear that the results of Example 3 are not due to optical resolution.

Claims (1)

[Claims] 1. General formula (At least one of R ₁ to _{R 4} in the formula is an alkyl, alkenyl, alkynyl, aralkyl, aryl, alkoxy, aryloxy group, etc., and the others are hydrogen-containing compounds of the formula to be stably present, and cyclodextrin and without hindering the inclusion of
Further, it is any organic residue that does not prevent halogenation of a carbon-carbon unsaturated bond, and is a group that can be interconnected to form a ring. Examples of such organic residues include nitro groups, cyano groups, halogens, carboxyl groups, carbonyl groups, hydroxyl groups, alkoxy groups, and the above-mentioned alkyl, allyl, aryl, alkynyl, ararykyl, and alkenyl groups substituted with these groups. Furthermore, R ₁ and R ₂ and R ₃ and R ₄ must not be the same residue at the same time. 1. A method for producing an optically active halogenated hydrocarbon, which comprises including an ethylenically unsaturated compound represented by the following formula in cyclodextrin, and then contacting the cyclodextrin with hydrogen halide.