JPH0350742B2 - - Google Patents

Description

[Detailed description of the invention] [Industrial application field]

The present invention provides (±)-1-phenyl-2-(para-
This invention relates to an improvement in a method for producing optically active PTE by optically resolving tolyl)ethylamine (hereinafter abbreviated as "(±)PTE").

[Conventional technology]

Optically active PTEs include efuedrin, quinine,
Like naturally occurring basic optical resolving agents such as brucine, it is widely used as an optical resolving agent for racemic acid, and is known to be used as an optical resolving agent for chrysanthemum acid, which is particularly effective as an insecticide. Therefore,
It would be desirable to have a simple and low cost method for producing optically active PTE. As a known optical resolution method for PTE, there is a method using (-)-aspartic acid as a resolving agent (West German Patent No. 2023426). According to this method, one enantiomer can be obtained in a pure form, but it is troublesome to obtain the other enantiomer in a pure form, and the diastereomeric salt must be decomposed.
It is necessary to collect PTE, generate diastereomeric salts with different optically active acids, and perform fractional crystallization. As a result of research on the optical resolution of (±)PTE, the inventors found that optically active mandelic acid, which is industrially available in large quantities and at low cost, is useful as a resolving agent. Furthermore, the inventors (±)
We have found that unique diastereomeric salts can be obtained by selecting a medium for the optical decomposition of PTE with mandelic acid.

[Problem to be solved by the invention]

An object of the present invention is to provide a method for efficiently producing optically active PTE with high purity and high yield by utilizing the above knowledge.

[Means to solve the problem]

The method for producing optically active PTE of the present invention involves producing (±)PTE in a solvent with optically active mandelic acid (hereinafter referred to as
(abbreviated as “(+)MA” or “(-)MA”)
In the method for producing optically active PTE, which consists of precipitating a diastereomeric salt and separating and obtaining (+)PTE or (-)PTE from this salt, the solvent is a water-lower alcohol mixed solvent or By selectively using an organic solvent selected from alcohols, ketones, and esters, diastereomeric salts containing optically active substances of the same sign, i.e., (+)PTE・(+)MA or (−)PTE・(-) MA, or a combination of optically active substances of opposite sign, i.e. (+)
PTE・(−)MA or (−)PTE・(+)MA
It is characterized by precipitating. A water-lower alcohol mixed solvent that provides a diastereomer salt formed by bonding optically active substances with the same sign has a volume ratio of water and a lower alcohol such as methanol or ethanol, which is centered around 1:1 and 0.5:
It is a mixture within the range of 1.5 to 1.5:0.5. Representative examples of alcohols, ketones, and esters, which are solvents that yield diastereomer salts formed by bonding optically active substances of opposite signs, are isopropyl alcohol, acetone, and ethyl acetate, respectively.

[Effect]

The operation of dividing (+)PTE to obtain an optically active substance is similar in principle to known techniques;
PTE (+) MA or (-) MA, preferably in equimolar proportions, is placed in any of the above solvents,
Heat to dissolve, cool to create a supersaturated solution, and leave to precipitate the diastereomeric salt.
At this time, add a small amount of salt crystals to be precipitated.
Inoculation is preferred. As mentioned above, when a water-lower alcohol mixed solvent is used as a solvent, the salt of the same sign (+) PTE.
(+)MA or (-)PTE/(-)MA precipitates, and when an organic solvent is used, a salt of the opposite sign (+)
Since PTE/(-)MA or (-)PTE/(+)MA will precipitate, use one of the solvents to precipitate salts of the same or opposite sign, and then evaporate the mother liquor to dryness. By repeating the operation of precipitating salts of different or the same sign using the other solvent, it is possible to alternately obtain salts of the same sign and salts of opposite sign using only one type of optical resolution agent. can. MA of optically active PTE thus obtained
After recrystallizing the salt from the same solvent as the one used for crystallization, if necessary, the optically active PTE is separated by decomposing the salt with the action of a base such as sodium hydroxide or ammonia. . this,
Optically pure (+) or (-) can be obtained by extraction with an organic solvent such as ether or benzene and distillation.
PTE is obtained. Example 1 (±) PTE6.97g [[α] ²⁰ ₅₈₉ = -6.4° (c = 1.35
,
Methanol)] and (-) MA (5.02 g) were added to 200 ml of a mixed solvent of water:methanol = 1:1, heated to dissolve, and then cooled to room temperature. This solution was inoculated with 0.11 g of (-)PTE/(-)MA salt,
After standing overnight, the precipitated crystals were filtered and 4.42
g of (-)PTE/(-)MA salt was obtained. Melting point: 148-152℃ [α] ²⁶ ₄₃₅ = -234.8° (c = 1.10, methanol) Add 30ml of 3N-NaOH aqueous solution to this (-)PTE/(-)MA salt to decompose the salt, and perform ether extraction. By distillation, 2.56 g of (-)PTE was obtained. [α] ³² ₅₈₉ = -60.2° (c = 1.19, methanol) Optical purity 96.9% When the liquid obtained by filtering off the precipitated crystals was evaporated to dryness under reduced pressure, 7.30 g of solid remained. 146 ml of isopropyl alcohol was added to this, heated to dissolve, and then cooled to room temperature. In this solution (+)
0.05 g of PTE/(-)MA salt was inoculated and left overnight. Separate the precipitated crystals by filtration and collect (+)PTE・(-)
3.69g of MA salt was obtained. Melting point: 175-177℃ [α] ³² ₄₃₅ = +60.6° (c = 1.01, methanol) Decompose this (+)PTE/(-)MA salt with 30ml of 2N-NaOH aqueous solution and distill the ether extract. As a result, 2.01 g of (+)PTE was obtained. [α] ³² ₅₃₉ = +58.7° (c = 1.05, methanol) Optical purity 94.5% Example 2 (±) 13.01 g of PTE and (+) 9.37 g of MA in 330 ml of a mixed solvent of water:methanol = 1:1 In addition,
The mixture was heated to dissolve and then cooled to room temperature. Approximately 3 mg of (+)PTE/(+)MA salt was inoculated into this solution,
After standing for 2 days, the crystals were filtered off to obtain 7.51 g of (+)PTE/(+)MA salt. Melting point 148-150℃ [α] ²⁵ ₄₃₅ = +237.8° (c = 0.980, methanol) Decompose this (+)PTE/(+)MA salt with 45ml of 3N-NaOH aqueous solution and distill the ether extract. As a result, 3.99 g of (+)PTE was obtained. [α] ²⁶ ₅₈₉ = +60.2° (c = 1.31, methanol) Optical purity 96.9% The mother liquor from which the salt crystals were filtered off was evaporated to dryness under reduced pressure, leaving 14.13 g of solid. 280 ml of isopropyl alcohol was added to this, heated to dissolve, and then cooled to room temperature. (-)PTE・
Approximately 3 mg of (+) MA salt was inoculated, and after standing overnight, the precipitated crystals were filtered out and 8.26 g of (-) PTE.
(+)MA salt was obtained. [α] ²⁴ ₄₃₅ = -61.4° (c = 1.13, methanol) This (-)PTE/(+)MA salt was decomposed with 50 ml of 3N-NaOH aqueous solution, and the ether extract was distilled to produce (-)PTE4. I got .68g. [α] ²⁷ ₅₈₉ = -59.4° (c = 1.20, methanol) Optical purity 95.7% Example 3 In Example 2, the (-)PTE/(+)MA salt was filtered off and the remaining mother liquor was evaporated to dryness under reduced pressure. Upon solidification, 6.14 g of residual solid was obtained. In this solid,
6.43 g of (+) PTE, 4.63 g of (+) MA and 250 ml of a mixed solvent of water:methanol=1:1 were added, heated to dissolve, and then cooled to room temperature. Approximately 3 mg of (+)PTE/(+) MA salt was inoculated into the solution, left overnight, and then the crystals were filtered out to form (+)PTE/(+)
5.37 g of crude crystals of MA salt were obtained. [α] ²⁵ ₄₃₅ = +235.4° (c = 1.03, methanol) The above crude (+)PTE/(+)MA salt was purified by recrystallizing it twice from a mixed solvent of water:methanol 1:1. (+)PTE・(+)MA salt 3.69
I got g. Melting point 150-152℃ [α] ²⁴ ₄₃₅ = +244.4° (c = 1.03, methanol) 1.05g of this purified (+)PTE/(+)MA salt 1N
By decomposing with 20 ml of -NaOH aqueous solution and distilling the ether extract, 0.15 g of (+)PTE was obtained. [α] ²³ ₅₈₉ = +62.1° (c = 1.09, methanol) Optical purity 100% When the mother liquor from which the crude (+) PTE and (+) MA salts were filtered off was evaporated to dryness under reduced pressure, it was 10.55 g of solid remained. 195 ml of isopropyl alcohol was added, heated to dissolve, and then cooled to room temperature. Approximately 3 mg of (-)PTE/(+)MA salt was inoculated, left overnight, and the crystals were filtered off.
6.32 g of crude crystals of (+)MA salt were obtained. [α] ²⁴ ₄₃₅ = -61.0° (c = 0.984, methanol) 5.30 g of this crude (-)PTE/(+)MA salt was recrystallized from 100 ml of isopropyl alcohol, and purified (-)PTE/(+)MA was obtained. 4.35 g of salt was obtained. Melting point 177-179℃ [α] ²³ ₄₃₅ = -67.1℃ (c = 1.05, methanol) By decomposing purified (-)PTE/(+)MA salt with 35ml of 2N-NaOH aqueous solution and distilling the ether extract. , (-)PTE・2.36g was obtained. [α] ²¹ ₅₈₉ = -61.6゜ (c = 1.21, methanol) Optical purity 99.2%

【Effect of the invention】

According to the method of the present invention, from (±)PTE to optically active PTE, i.e. (+)PTE and (−)PTE
diastereomeric salts containing can be obtained alternately using one type of optical resolving agent, i.e. (+)MA or (-)MA, by alternating the solvent in which its crystallization is carried out. can. Since it is easy to separate and obtain each optically active PTE from the obtained salt, optically active PTE can be efficiently produced by this method. The produced PTE has high optical purity and good yield.

Claims (1)

[Claims] 1 (±)-1-phenyl-2-(para-
Tolyl)ethylamine (hereinafter referred to as "(±)PTE") is reacted with optically active mandelic acid (hereinafter referred to as "(+)MA" or "(-)MA") to precipitate diastereomeric salts, and this salt In the method for producing optically active PTE, which comprises separating and obtaining (+)PTE or (-)PTE from
(+) as a diastereomeric salt by selectively using a lower alcohol mixed solvent or an organic solvent selected from alcohols, ketones, and esters.
PTE・(+)MA or (−)PTE・(−)
A manufacturing method characterized by precipitating MA, (+)PTE/(-)MA, or (-)PTE/(+)MA. 2. The manufacturing method according to claim 1, which is carried out using a water/methanol mixed solvent as the water-lower alcohol mixed solvent and isopropyl alcohol as the organic solvent.