JPS6136254A - Preparation of optically active sulfoxide - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an optical resolving agent very easily in high purity and yield, by reacting a racemate of a sulfoxide with optically active 1,1'-bi-2-naphthol. CONSTITUTION:A racemate of a sulfoxide expressed by the formula (R1 and R2 are mutually different lower alkyl) is reacted with optically active 1,1'-bi-2- naphthol in a solvent, e.g. benzene or ethyl acetate, at room temperature for several hours - some ten hours to give a clathrate compound, which is then separated and decomposed with silica gel, etc. to afford the aimed compound. The amounts of the sulfoxide and the 1,1'-bi-2-naphthol to be used are 2:1 molar ratio, and either one is used in an excess amount if necessary to carry out the reaction.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention provides a novel method for producing optically active sulfoxides, more specifically, a method for producing optically active sulfoxides as an optical resolving agent by directly optically resolving a racemic form of sulfoxides. The present invention relates to an industrially advantageous method by which useful optically active sulfoxides can be produced extremely easily with high purity and high yield.

Sulfoxides in which two different substituents R and R' are bonded to a sulfoxide group exist in two types of optical isomers, (+) and (-), in which the sulfur atom is an asymmetric atom. It is known to do.

By the way, for sulfoxides in which R and R' are different lower alkyl groups, there is no known method to obtain an optically active form by optically resolving the corresponding racemic form. ↓ ←)-menthyl 1-butanesulfinate ↓ + methermagnesium firomide (10)-methyl-n-furobyl sulfoxide A method for obtaining an optically active substance [K. Mislowet
al-; J. Am. Chem. SOC. , 87.
1958 (1965)] is known.

Problems to be Solved by the Invention However, this method has problems such as requiring very special reagents, involving numerous steps requiring complicated operations, and having a low yield. .

It was unsuitable for industrial implementation.

In view of these circumstances, the present inventors have conducted extensive research to provide an industrial method for obtaining optically active sulfoxides with high purity and high yield by directly resolving racemic sulfoxides. As a result, they discovered that the purpose could be achieved by using optically active β-dinanafur.
Based on this knowledge, we have completed the present invention.

Means for solving the problems, that is, the present invention provides a racemic body of sulfoxides represented by the general formula % (1) (in which R1 and R2 are different lower alkyl groups), . Reacting the optically active form of 1'-bi-2-naphthol to produce an inclusion compound of the optically active form of the sulfoxides and the optically active form of 1.1'-bi-2-naphthol, and separating this. The present invention provides a method for producing optically active sulfoxides, which is characterized in that the optically active sulfoxides are then decomposed to obtain optically active forms of the sulfoxides.

The sulfoxides represented by the general formula (1) that are optically resolved by the method of the present invention are known compounds and are usually obtained as racemates. R1 and R2 in the general formula ([) are different lower alkyl groups, such as a methyl group or an ethyl group.

These include n-propyl group, n-butyl group, 1SO-butyl group, and the like. Further, these groups may be substituted with an inert substituent such as a nohalogen atom or an alkoxy group. Specific examples of such sulfoxides include methyl-n
-butyl sulfoxide, methyl-iso-butyl sulfoxide, methyl-n-propylsulfoxide, methyl-
Examples include ethyl sulfoxide, ethyl-n-bunal sulfoxide, and ethyl-n-propylsulfoxide. Among these, those that can be optically resolved particularly preferably are methyl-n-butyl sulfoxide and methyl-iSO.
-butyl sulfoxide, methyl n-furovir sulfoxide, methyl-ethyl sulfoxide.

On the other hand, 1,1'-bi2- used as an optical resolving agent
Optically active forms of naphthol are also known. It is easily available as a commercial product. This optically active form of l,1'-bi-2-naphthol has the following q-form structure (
R) − (+1 and (S) − (−)) exist as two O enantiomers.

The (R) − (+) integral and (S) − (−) integral exhibit decorative dust at +37.7° and −37.7°, respectively, in tetrahydrofuran, but in the method of the present invention, teeth.

Any of these enantiomers can be used. And when (R) − (+) is used,
This is the combination of (g) sulfoxides and (S) −
(−) When using monolithic sulfoxides, (
-) selectively combine with each other to form an inclusion compound with a molar ratio of 1°1.

In order to perform optical resolution of sulfoxides according to the method of the present invention, the racemic form of sulfoxides is dissolved in a suitable solvent, 1,1'-bi-2-naphthol is added thereto, and the mixture is heated at room temperature for several hours to 10 hours. Leave it for several hours. in this case,
In order to promote the dissolution of each raw material component or to promote the precipitation of the formed clathrate compound, heating or cooling can be performed as desired.

The amount of sulfoxide and 1,17-bi-2-naphthol to be used is preferably a molar ratio of about 2=1, but if desired, either one can be used in excess.

Examples of solvents include aliphatic hydrocarbons such as hexane, heptane, kerosene, and petroleum ether, ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene, toluene, and xylene, diethyl ether,
Dipropyl ether.

Ethers such as tetrahydrofuran, methanol,
Alcohols such as ethanol and esters such as ethyl acetate and butyl acetate are used. These may be used alone or in combination of two or more.

Next, the clathrate crystals precipitated as described above are filtered out, purified by recrystallization as necessary, and then dissolved in a solvent and treated with silica gel, alumina gel, silica-alumina gel, etc. By doing 1,
It decomposes into an optically active form of 1'-bi-2-naphthol and an optically active form of sulfoxides.

In addition, instead of processing with silica gel or alumina gel, it is possible to treat each component optically with an alkali such as sodium hydroxide or potassium hydroxide, or to perform distillation under mild conditions that do not cause racemization. It can also be decomposed into active forms.

In this way, highly purified optically active forms of sulfoxides can be obtained in high yield.

Effects of the Invention The method of the present invention is a method for directly optically resolving racemic forms of sulfoxides to industrially advantageously produce optically active forms of sulfoxides. According to this method, optically active forms of sulfoxides are extremely It is easily obtained with high purity and high yield. The obtained optically active form of sulfoxides selectively forms clathrate compounds with optically active components, and is therefore useful as an optical resolution agent.

EXAMPLES Next, the invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples in any way.

Example 1 Racemic form of methyl-n-butyl sulfoxide 1.682
and (R)-(t)-1,1'-bi-2-naphthol [[
α], +37.7° (in tetrahydrofuran)]2,
OOr was dissolved in benzene 10-, n-hexane 10- was added thereto, and after leaving it at room temperature for 12 hours, it precipitated. A clathrate compound consisting of mol and 1 mol of ←)-methyl-n-butyl sulfoxide was collected by filtration, recrystallized twice with 20 m/m of benzene, and dried to obtain colorless prismatic crystals.
Melting point: 152-155°C, [α]. +55.8° (in ethanol)] 2.14r was obtained.

Next, the crystals were passed through a silica gel column using a mixture of equal amounts of benzene and ethyl acetate as an elution solvent to obtain (+)-methyl-n-butyl sulfoxide 0.639.

Example 2 Racemic form of methyl-iso-butyl sulfoxide 0,8
4IP and proviso) - (+) - 1. 1'-B2-naphthol [[α. :], + 37.7° C in tetrahydrone run)]1,0Or was dissolved in benzene 5-, n-hexane 5- was added thereto, and after standing at room temperature for 12 hours, the precipitated (R)- A clathrate compound consisting of 1 mole of (t)-1,1'-bi-2-naphthol and 1 mole of (t)-methyl-iso-butyl sulfoxide was filtered and 57% of benzene was added. by recrystallizing it five times and then drying it.

Colorless prismatic crystal [melting point 122-124℃, [α]9+5
5,4° (in ethanol)] 0.43 g was obtained.

Next, the crystals were passed through a silica gel column using an equal mixture of benzene and ethyl acetate as an elution solvent, resulting in (t)-methyl-is.

-Butyl sulfoxide [[α,]. +109° (in ethanol) ] 0.12 fI was obtained.

Example 3 Racemic form of methyl-n-propylsulfoxide 0.74
fI and (R)-(t)-1,1'-bi-2-naphthol [[α], +37.7° (in tetrahydrofuran)
] 1.00 g is dissolved in benzene 5-, and n-
After adding hexane 5- and leaving it at room temperature for 12 hours, the precipitated sail)-(t)-1,17-bi-2-naphthol 1
The clathrate compound consisting of 1 mole of ruto(+)-methyl-n-propylsulfoxide was collected by filtration and diluted with 10-benzene.
After recrystallization, it is dried.

Colorless prismatic crystals [melting point 157-160°C, [α].

+54.2° (in ethanol)] 1.0 Or was obtained.

The crystals were then passed through a silica gel column using an equal mixture of benzene and ethyl acetate as the elution solvent, resulting in ←)-methyl-n-propylsulfoxide [[α], + 123° (in ethanol) ) 0.
I got 27g.

Example 4 Racemic form of methyl-ether sulfoxide 0.642 and tri-(t)-1,1'-bi-2-naphthol [[α]].

+ 37.7° (in 7 runs of tetrahydro)] 1.00
Ritowohenzen 5m/! After adding 5 ml of n-hexane and leaving it at room temperature for 12 hours, (R) -(+) -1,1'-bi-2-naphthol 1 was precipitated.
A clathrate compound consisting of 1 mole of (+)-nonaluethylsulfoxide was collected by filtration, recrystallized once with benzene 5- and dried to give colorless prismatic crystals [melting point 124-127°C]. , [α]9+ 30.5° (in ethanol) 30.5 (J/) was obtained.

In the next step, the crystals of were passed through a silica gel column using an equal mixture of benzene and ethyl acetate as the elution solvent, resulting in (t)-methyl-ethyl sulfoxide [
[α], +39.1° (in ethanol)] 0.14F
I got it.

Claims (1)

[Claims] 1 A racemic body of sulfoxides represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (R_1 and R_2 in the formula are different lower alkyl groups), 1,1' - Reacting the optically active form of bi-2-naphthol to produce an inclusion compound of the optically active form of the sulfoxides and the optically active form of 1,1'-bi-2-naphthol, which was separated. A method for producing optically active sulfoxides, which comprises subsequently decomposing the sulfoxides to obtain optically active forms of the sulfoxides.