JP3034086B2 - Method for producing optically active ether - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing an optically active ether by dehydrating an optically active alcohol. More specifically, the present invention relates to a method for producing an optically active ether by subjecting a secondary or tertiary optically active alcohol to a dehydration reaction in a solid state.

[0002]

2. Description of the Related Art Conventionally, various reaction methods have been known as methods for producing ether compounds. That is, a method of dehydrating alcohol, a method of reacting various alkyl compounds such as alkyl halides, sulfates or sulfonates known as Williamson synthesis with metal alkoxide compounds, various alcohol compounds and diazomethane. Many methods are known, such as a method based on a methylation reaction of an alcohol, or an addition reaction of an alcohol to various olefin compounds. In addition to the above methods, various other reaction methods can be used for synthetic organic chemistry, but the above-mentioned methods are exemplified as simple and representative methods.

Conventionally, even if the optically active alcohol is dehydrated by a conventional method in order to obtain an optically active ether, it is very difficult to carry out the reaction while maintaining the steric state. I could not get ether.
Similarly, when reacting various alkoxides with various alkyl compounds, it is very difficult to carry out the etherification reaction while maintaining the steric condition, that is, the optically active ethers using optically active alcohols as raw materials. Was not known at all.

[0004] Although the synthesis of the gas phase method is not mentioned, ether production by the conventional liquid phase method is generally carried out using a solvent. It aims at improving the reactivity such as solvation with a solvent and facilitating the control of the heat of reaction. In the case of reacting a raw material which is solid under the reaction conditions, it has been a general method to dissolve it in a solvent once and react in a homogeneous solution state. .

However, recently, attempts have been made to carry out an organic reaction in a solid state. For example, J. Chem.
Soc. Chem. Commun. , (1988) 9
58-959 discloses Baeyer-Villi performed on a solid phase.
Ger reaction is described in Org. Chem. , (1989)
54 , 3007-3009, discloses an oxidative coupling reaction of phenols carried out in a solid phase. Let
t. , (1990) 373-376 report a benzyl acid transfer reaction and the like performed in a solid phase.
These are reacted without using any reaction solvent,
Not only is it a reaction system that could not be considered from the common sense of conventional chemical reactions, but it is also remarkable that the reaction rate is faster and the reaction yield is often higher than the reaction in the solution state using the corresponding solvent. Characteristics have already been found.

[0006] Similarly, an ether formation reaction by a solid-state dehydration reaction using alcohol as a raw material is also described in J. Am.
Chem. Soc. Chem. Commun. , (1
990) 1270-1271. Here, too, it has been found that the reaction yield is higher under milder conditions than the corresponding dehydration reaction in the solution state.

[0007]

An object of the present invention is to produce an optically active ether by dehydrating an optically active alcohol.

[0008]

Means for Solving the Problems The present inventor has proposed an optically active alcohol in a method for producing an ether from alcohol, which is the simplest method for producing an ether. We have been studying a method of producing optically active ethers by dehydrating while maintaining the three-dimensional shape as a raw material. It has been found that a reaction while maintaining the steric state selectively occurs, which could not be imagined from the solution reaction, and the present invention has been completed.

That is, the present invention provides a method for producing an optically active ether, comprising dehydrating at least one optically active alcohol with a secondary or tertiary alcohol in a solid state. Things.

The present invention will be described in more detail. As the raw material alcohol that can be used in this reaction, any alcohol can be used as long as it is in a solid state under the reaction conditions. Therefore, any secondary or tertiary optically active alcohol may be used as long as it satisfies the condition of a solid phase.

[0011]

Embedded image (Where X represents hydrogen, an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, a nitro group, or a halogen)
An optically active alcohol represented by the following formula can be used. For example, a secondary or tertiary optically active alcohol having an alkyl group such as tert-butyl group, phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, o-chlorophenyl group, p-bromophenyl Group, p-methoxyphenyl group,
Examples thereof include secondary or tertiary optically active alcohols having one or two or more different aromatic groups such as a biphenyl group, a phenoxyphenyl group, and a p-nitrophenyl group.

In the present invention, optically active ethers can be selectively produced from the above-mentioned alcohols by a dehydration reaction of a combination of one or more alcohols.
When two or more alcohols are subjected to a dehydration reaction, at least one alcohol may be an optically active substance.
In addition, in the dehydration reaction of one kind of optically active alcohol, an optically active ether which does not substantially generate a meso form is produced.

In the present invention, a catalyst such as an acid is used for the dehydration reaction of alcohol in a solid state. The acid that can be used is preferably an acid capable of maintaining a reaction state in a solid phase. Examples of such an acid include trihaloacetic acids such as trichloroacetic acid, p-toluenesulfonic acid monohydrate or sulfonic acid type. Examples include organic sulfonic acids such as strongly acidic cation exchange resins, heteropoly acids such as Nafion, silicomolybdic acid, silicotungstic acid, phosphomolybdic acid or phosphotungstic acid, and inorganic or organic acids such as hydrochloric acid gas and high silica zeolite. You can do it.
They can be used in any amount from a catalyst amount of 0.1 mol% to the starting alcohol to a stoichiometric amount or more.

The method of the dehydration reaction is to crush or grind the optically active solid alcohol as a raw material into a powder, mix it well with an acid, and at any temperature and for any time at which the solid state can be maintained. Desirably, it can be carried out simply by leaving it for about 5 minutes to 12 hours. Further, as other charging methods, a method in which crystals are simultaneously precipitated from a solution in which different kinds of raw material alcohols are dissolved, a mixed crystal, a complex form, or a mixture of these different kinds of alcohols is used. It is possible to react even one that has been mixed and then re-solidified. During the reaction, a method may be adopted in which the reaction is carried out while stimulating the mixture appropriately by applying ultrasonic waves, but in particular, a continuous stirring operation is not required. After the completion of the reaction, the desired optically active ether can be obtained by a conventional method. For example, it is directly recovered by distillation, or once dissolved and extracted with a solvent such as ether, washed with water, and then separated. to recover.

[0015]

The present invention will be described in more detail with reference to the following examples. Example 1

[0016]

Embedded image Optically active solid alcohol (2) ([α] D-2.4 ゜ (c = 0.41, MeOH) 0.2 g (1.01 mmol)
l) and p-toluenesulfonic acid in a solid phase
Left for hours. (After mixing with the solid, the mixture spontaneously melted in about 5 minutes.) Thereafter, water was added and ether extraction was performed, and the mixture was thoroughly washed with saturated aqueous sodium hydrogen carbonate and water. After drying, it was concentrated to give 0.2 g of a pale yellow oil, which was further purified by column chromatography on silica gel to give 0.19 g of a pale yellow oil.
Tell (3) was obtained. [Α] D-3.0 ° (c = 0.27, MeOH) By comparison with analytical data of a standard sample obtained separately, etherification by dehydration reaction at 100% Retention was found. Was happening. Example 2

[0017]

Embedded image (R, R)-(-)-1,6-diphenyl-1,
6-bis (o-chlorophenyl) hexa
When -2,4-diyne-1,6-diol was recrystallized from methanol, colorless prism crystals (mp: 125 to 126 ° C) represented by (4) were obtained.

The Complex 0.5g and 0.17g
And p-toluenesulfonic acid in a mortar.
(Where it became slightly wet, but did not melt.) After standing at room temperature for 2 hours, water was added, and the mixture was extracted with ether, and washed well with saturated aqueous sodium hydrogen carbonate and water. After drying, concentration was performed to obtain 0.49 g of a brown solid, which was further purified by column chromatography on silica gel to obtain 0.16 g of crystal (5) (yield: 35%). [Α] D-94 ゜ (c = 0.49, MeOH), mp:
141-143 ° C. By comparison of analytical data with a separately synthesized standard sample, the ee of the (R, R) -isomer was 94%.

[0019]

As described above, according to the present invention, an optically active ether having a high optical purity can be obtained very easily by causing a dehydration reaction of an optically active alcohol in a solid phase. That is, the most readily available raw material, alcohol, can be used as it is, and can be easily converted to optically active ether by the most easily carried out reaction method, dehydration reaction. Is what you do.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI B01J 31/02 103 B01J 31/02 103 31/04 31/04 31/08 31/08 C07B 53/00 C07B 53/00 G C07C 41/09 C07C 41/09 43/164 43/164 43/17 43/17 43/178 43/178 43/205 43/205 A 43/275 43/275 205/34 205/34 // C07B 61/00 300 C07B 61/00 300 (58) Fields investigated (Int. Cl. ⁷ , DB name) C07B 41/04 B01J 31/02 103 C07B 53/00 C07C 41/09 C07C 43/164 C07C 43/17 C07C 43 / 178 C07C 43/205 C07C 43/275 C07C 205/34 C07B 61/00 300

Claims (4)

(57) [Claims] 1. A method for producing an optically active ether, comprising subjecting at least one optically active alcohol to a dehydration reaction in a solid state with a secondary or tertiary alcohol. 2. The method for producing an optically active ether according to claim 1, wherein the dehydration reaction is carried out in the presence of an acid catalyst. 3. A compound of the general formula (1) (Where X represents hydrogen, an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, a nitro group, or a halogen)
A secondary or tertiary alcohol having at least one phenyl group or substituted phenyl group at the α-position represented by the formula: wherein at least one optically active alcohol is subjected to a dehydration reaction in a solid state. A method for producing an optically active ether. 4. The method for producing an optically active ether according to claim 3, wherein the dehydration reaction is carried out in the presence of an acid catalyst.