JPS6114127B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel method for producing an optically active dihalogen compound, and more specifically, the present invention relates to a novel method for producing an optically active dihalogen compound, and more specifically,

[Formula] (At least one of R ₁ to R ₄ in the formula is alkyl, alkenyl, alkynyl, ararykyl, aryl,
Any organic compound such as an alkoxy or aryloxy group, others containing hydrogen, which allows a compound of the formula to exist stably and does not prevent inclusion or addition of halogen to a carbon-carbon unsaturated bond. It is a residue that can also be linked together 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 (X is a halogen group). 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.Inc.Ed Engl., 8608 (1969)], where it was achieved not only by using optically active starting materials but also by using larger single crystals. Therefore, this method
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. 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 cyclodextrin, gaseous halogen was applied to the solid clathrate compounds. After that, by recovering the halide from the clathrate, we successfully synthesized an optically active halogenated hydrocarbon. 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 in which appropriate chemical groups are 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 halogen 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

[Formula] (At least one of R ₁ to _{R 4} in the formula is an alkyl, alkenyl, alkynyl, ararykyl, aryl, alkoxy, aryloxy group, etc., and the others contain hydrogen, so that the compound of the formula exists stably, Also, it is any organic residue that does not hinder inclusion with cyclodextrin or the addition of halogen to a carbon-carbon unsaturated bond, and is a group that can be interconnected to form a ring. These organic residues include the above-mentioned, alkyl,
These include allyl, aryl, alkynyl, ararykyl, and alkenyl 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,
Aromatic hydrocarbon acids such as - and m-, p-methylcinnamic acid, cinnamylideneacetic acid, o- and m-, p-hydroxycinnamic acid, and their alkyl, alkenyl, alkynyl, ararykyl,
There are 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. Vinyl fluoride, vinyl bromide, allyl chloride, allyl bromide, allyl iodo, trichloroethylene, 1,2-dichloroethylene, 1-phenyl-3-bromopropene-1, o- and m-, p-chlorostyrene, etc. These include halogen-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 (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 pickling machine, 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. Halogen gas is blown into the clathrate compound of the unsaturated compound thus obtained in powder form while blocking light, and the mixture is heated at -50°C to 90°C, preferably -20°C to 50°C.
and react for 15 minutes to 150 hours, preferably 30 minutes to 50 hours. The reaction temperature and time should be selected appropriately depending on the stability of the clathrate, the reactivity of the clathrated unsaturated compound, the reactivity of the halogen added, and the stability of the dihalide produced. be. After the reaction, excess unreacted halogen gas is removed under vacuum, followed by extraction with a suitable solvent such as diethyl ether to obtain the desired optically active dihalide from the clathrate. The halogen gas used in the present invention may be any of fluorine, chlorine, bromine, and iodine gas. Next, the present invention will be explained in more detail with reference to Examples. Example 1 120 g of β-cyclodextrin is added to 900 ml of water and heated to 50° C. while stirring. 10 g of methacrylic acid was added to the resulting solution, and the mixture was stirred while heating at 40° C. for about 2 hours, then allowed to cool, and the resulting precipitate was filtered to obtain a clathrate compound. The obtained clathrate compound was vacuum dried for 24 hours. This clathrate compound was placed in a sealed container and exposed to bromine gas at 50°C for 5 hours without exposing it to light.
Unreacted bromine gas was removed under vacuum. The reacted bromide was extracted with diethyl ether and chromatographed using a silica gel column and 1.2 dichloroethane to obtain 2.3-dibromoisobutyric acid. [α] ²⁵ _D was +2.5 when the yield was 90% and the concentration in methanol was 0.59 g/100 ml. Elemental analysis values Calculated values C = 19.53% H = 2.44% Br = 65.01% Analysis values C = 19.47% H = 2.48% Br = 65.08% Example 2 Add 200 g of α-cyclodextrin to 1600 ml of water and stir to approx. Heat to ℃ to make a homogeneous solution. Add 20g of methacrylic acid to this for about 3 hours.
After heating to 40°C with stirring, the mixture was allowed to cool, and the resulting precipitate was filtered to obtain a clathrate compound. After drying this clathrate compound, it was placed in a sealed container and exposed to bromine gas at 45° C. for 50 hours without exposure to light, and then unreacted bromine gas was removed under vacuum. The bromide was extracted with diethyl ether and 2.
3-dibromoisobutyric acid was obtained. [α] ²⁵ _D measured at a yield of 30% and a concentration in methanol of 0.50 g/100 ml was -1.0. Elemental analysis values Calculated values C = 19.53% H = 2.44% Br = 65.01% Analysis values C = 19.58% H = 2.39% Br = 64.93% Example 3 Add 600 ml of water to 200 g of β-cyclodextrin to make a paste, and make malein. Add 15g of acid to 7
Knead at room temperature for an hour. The clathrate compound was obtained by drying using a spray drying method. This clathrate compound was placed in a sealed container and exposed to bromine gas at 50° C. for 8 hours without exposure to light, and then unreacted bromine gas was removed under vacuum. The reacted bromide was extracted with diethyl ether to obtain 2,3-dibromobutane-1,4-dibasic acid. Yield 2%, concentration in dichloroethane 0.62g/100
[α] ²⁵ _D measured in ml was −22.0, and the optical yield was 15%. Elemental analysis values Calculated values C = 17.40% H = 1.45% Br = 57.94% Analysis values C = 17.36% H = 1.42% Br = 57.89% Example 4 Trans-cinnamic acid obtained in the same manner as Example 1 Similarly, bromine gas was applied to the β-cyclodextrin clathrate compound at 0°C for 5 hours, and the yield was 3.
% of 2,3-dibromo-3-phenylpropanoic acid was obtained. [α] ²⁵ _D measured at a concentration of 0.55 g/100 ml in ethanol was −27.5, and the optical yield was 40%. Elemental analysis values Calculated values C = 35.09% H = 2.60% Br = 51.92% Analysis values C = 35.12% H = 2.57% Br = 51.96% Example 5 α-Cyclodextrin of crotonic acid obtained by the same operation as in Example The clathrate compound was placed in a sealed container and exposed to chlorine gas at 25°C for 10 hours without exposure to light, and then unreacted chlorine gas was removed under vacuum. Extraction of the chloride with dichloroethane yielded 2,3-dichloro-butanoic acid. [α] ²⁵ _D measured at a yield of 10% and a concentration in methanol of 0.40 g/100 ml was +2.7. Elemental analysis values Calculated values C = 30.59% H = 3.82% Cl = 45.19% Analysis values C = 30.62% H = 3.73% Cl = 45.10% Example 6 α- of crotonic acid obtained by the same operation as Example 2
The cyclodextrin clathrate compound was treated with bromine gas at 45° C. for 30 hours, and then treated in the same manner as in Example 2 to obtain 2,3-dibromobutanoic acid in a yield of 20%. [α] ²⁵ _D measured at a concentration of 1.00 g/100 ml in methanol was +1.0. Elemental analysis values Calculated values C = 19.53% H = 2.44% Br = 65.01% Analysis values C = 19.60% H = 2.36% Br = 64.96% Example 7 β- of cinnabar nitrile obtained in the same manner as Example 1 The cyclodextrin clathrate compound was exposed to bromine gas at 0° C. for 5 hours and treated in the same manner as in Example 1 to obtain 2,3-dibromo-3-phenylpropanenitrile in a yield of 70%. [α] in ethyl acetate
²⁵ _D was -26. Elemental analysis values Calculated values C = 37.40% H = 2.42% Br = 55.33% Analysis values C = 37.31% H = 2.40% Br = 55.2% Example 8 β-Cyclo of cinnamic alcohol obtained in the same manner as Example 1 Dextrin clathrate at -5℃
Bromine gas was applied for 10 hours, and the same treatment as in Example 1 was performed to obtain 2,3-dibromo-3-phenylpropanol in a yield of 46%. [α] ²⁵ _D in ethyl acetate
was -8.0. Elemental analysis values Calculated values C = 36.76% H = 3.40% Br = 54.39% Analysis values C = 36.70% H = 3.43% Br = 54.19% Example 9 α- of cinnamic aldehyde obtained in the same manner as Example 2 The cyclodextrin clathrate compound was treated with bromine gas at 30° C. for 6 hours and treated in the same manner as in Example 2 to obtain 2,3-dibromo-3-phenyl-propanal in a yield of 60%. [α] ²⁵ _D in ethyl acetate was -4.7. Elemental analysis values Calculated values C = 37.01% H = 2.74% Br = 54.76% Analysis values C = 37.13% H = 2.66% Br = 54.80% Example 10 Styrene α-cyclodextrin capsule obtained in the same manner as Example 2 The contact compound was exposed to bromine gas for 2 hours at 0°C and treated in the same manner as in Example 2 to obtain 1.
2-dibromo-2-phlethane was obtained with a yield of 90%. [α] ²⁵ _D in ethyl acetate was -33. Elemental analysis values Calculated values C = 36.39% H = 3.03% Br = 60.58% Analysis values C = 36.30% H = 3.06% Br = 60.45% Example 11 α-Cyclodextrin clathrate of o-methylstyrene at 5°C Bromine gas was applied for 12 hours, and the same treatment as in Example 2 was performed to obtain 1,2-dibromo-2-(2-methylphenyl)-ethane in a yield of 20%. [α] ²⁵ _D in ethyl acetate was -29.6. Elemental analysis values Calculated values C = 38.88% H = 3.60% Br = 57.52% Analysis values C = 38.94% H = 3.57% Br = 57.50% Example 12 Add 100 g of γ-cyclodextrin to 100 ml of water and stir to approx. 5 g of allylbenzene was added to the solution obtained by heating to 40° C., and the mixture was stirred while heating at 40° C. for about 3 hours, then allowed to cool, and the resulting precipitate was filtered to obtain a clathrate compound. After drying the obtained clathrate compound, it was treated with bromine gas at 0°C for 3 hours, and then treated in the same manner as in Example 1 to obtain 1,2-dibromo-3-phenylpropane in a yield of 50%. Ta. [α] ²⁵ _D in ethyl acetate was -0.9. Elemental analysis values Calculated values C = 38.88% H = 3.60% Br = 57.52% Analysis values C = 38.80% H = 3.63% Br = 57.60% Example 13 Of cinnamate methyl ester obtained in the same manner as Example 1 The β-cyclodextrin clathrate compound was exposed to bromine gas at −5° C. for 20 hours, and then treated in the same manner as in Example 1 to obtain 2,3-dibromo-3-phenylpropanoic acid methyl ester. The yield was 40%, and the [α] ²⁵ _D in ethanol was +4.1. Elemental analysis values Calculated values C = 37.29% H = 3.11% Br = 9.94% Analysis values C = 37.19% H = 3.17% Br = 9.91% Example 14 β of cinnamate ethyl ester obtained in the same manner as Example 1 -25 cyclodextrin clathrates
After being exposed to chlorine gas for 20 hours at °C, it was treated in the same manner as in Example 1 to obtain 2,3-dichloro-3-phenylpropanoic acid ethyl ester. The yield was 64%, and the [α] ²⁵ _D in ethanol was +7.2. Elemental analysis values Calculated values C = 53.46% H = 4.86% Cl = 28.72% Analysis values C = 53.53% H = 4.90% Cl = 28.79% Example 15 Already proposed method [Wiedenhof et al.
Die Starke, 21, 119 (1969)] β-cyclodextrin polymer (average molecular weight
5000) and β-methylstyrene in the same manner as in Example 3, a poly(β-cyclodextrin) clathrate of β-methylstyrene was treated with bromine gas at 10°C for 15 hours to form a poly(β-cyclodextrin) inclusion compound of Example 3. Similar treatment yields 1,2-dibromo-1-phenylpropane.
Got it at 27%. [α] ²⁵ _D in ethyl acetate is −24.3
It was hot. Elemental analysis values Calculated values C = 38.88% H = 3.60% Br = 57.52% Analysis values C = 38.82% H = 3.62% Br = 57.60% In order to characterize the present invention, a comparative example is shown below. Comparative Example 1 Separately obtained racemic 2,3-dibromo-3-phenylpropanoic acid was prepared by the method of Kramer et al. [F.
Cramer, W.Dietsch; Chem.Ber.92 378
(1959)], optical resolution was performed using β-cyclodextrin. In this case, [α] ²⁵ _D is +2.5, which is the opposite sign, and the optical yield is also small, at 4%. Therefore, it is clear that the results of Example 4 are not due to optical resolution. Comparative Example 2 The β-cyclodextrin clathrate of cinnamic acid used in Example 4 was dissolved in dimethyl sulfoxide and treated in the same manner as in Example 4. At this time, compared to Example 4, the yield was as low as 4%, and [α] ²⁵ _D was also −
3.8, and the optical yield was small at 6%.

Claims (1)

[Claims] 1 Does not prevent inclusion with cyclodextrin,
Moreover, an ethylenically unsaturated compound having any organic residue that does not hinder the addition of halogen, and whose dihalogenated hydrocarbon can become an asymmetric compound, is included in cyclodextrin, and then light is irradiated. A method for producing an optically active dihalogenated hydrocarbon, which comprises bringing it into contact with a halogen while blocking it.