JPS59110656A - Optical resolution of 1-phenyl-2-(p-tolyl)ethylamine - Google Patents

Abstract

PURPOSE:Optically active mandelic acid is used as an optically resolving agent for (+ or -)-1-phenyl-2-(p-tolyl)ethylamine (PTE) to enable easy production of the titled compound used as an optically resolving agent for racemic acids, especially chrysanthemumic acid which is used as an insecticide of high purity and obtd. in high yield. CONSTITUTION:(+ or -)-PTE is combined with a stoichiometric amount of (+)- or (-)-mandelic acid and they are dissolved in a solvent such as alcohol, ketone or ester with heat to form a supersatturated solution. Then, the solution is cooled down to room temperature to effect optical resolution of (+ or -)-phenyl-2-(p-tolyl) ethylamine. The mandelic acid as a resolving agent is industrially available in a large scale at an inexpensive price.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to (±)-1-phenyl-2-(para-tolyl)
This relates to the optical resolution method of ethylamine (hereinafter abbreviated as (±)PTE).

Optically active PTE is widely used as an optical resolving agent for racemic acids, similar to basic natural optical resolving agents such as ephedrine, quinine, or purusin, and is particularly useful as a resolving agent for chrysanthemum acid, which is effective as an insecticide. is known,
A simple method for optical resolution of PTH is desired.

As the optical resolution method of PTE known so far, for example, there is a method using (+)-aspartic acid as a resolving agent (German Patent No. 2,023,426).
According to these methods, it is possible to obtain a pure form of one enantiomer, but in order to obtain a pure form of the other enantiomer, the diastereomeric salt must first be decomposed to recover the PTE, and then a different optically active substance must be obtained. It has the disadvantage that it requires a complicated operation of forming a diastereomeric salt with an acid and performing fractional crystallization.

(1) As a result of intensive studies on the optical resolution of PTE, the present inventors found that optically active PTE can be easily obtained by using optically active mandelic acid, which is industrially available in large quantities and at low cost, as a resolving agent. They discovered that it can be efficiently obtained with high purity and high yield, and completed the present invention.

That is, the present invention is a method for optically resolving PTE, characterized in that (1) optically active mandelic acid (hereinafter abbreviated as MA) is allowed to act on PTE as a resolving agent.

In the present invention, optically active MA ((+)MA or ←)M
A ) acts as a resolving agent (±) in a solvent.
When PTE is reacted with (+)MA, (+)P
T E・(+) M A salt and (−) P T E・(
When reacting +) MA salt or (-) MA salt, (-) P T E・(-) MA salt and (+) P
TE・(-)MA salt and the generated 2
It refers to the ability to separate different types of salts based on their solubility differences in solvents.

Next, the dividing method of the present invention will be specifically described. First (±)
Preferably, the equimolar amount of (
+) or (-) MA, add these (solvent, heat dissolve to make supersaturated, cool to room temperature, if necessary, after inoculating a small amount of optically active PTE-MA salt seeds, leave to stand, The same type of salts that precipitate are separated.

Solvents used here include alcohols, ketones,
Solvents commonly used for optical resolution operations such as esters or mixtures thereof with water may be used, but if a mixed solvent of water:methanol-1:1 (volume ratio) is used, salts (+) of the same sign (+) P T E・(+)MA Shiomaf,: e;t(
-1P T E・(-)M A salt precipitates, and if isopropyl alcohol is used, a salt of the opposite sign (+) P T E
-(-)MA salt or (-)PTE/(+)MA salt precipitates. Therefore, after removing the optically active salt using either the mixed solvent or isopropyl alcohol, the mother liquor is evaporated to dryness, and then it is treated with another solvent to remove the other optically active salt. By precipitating the crystals, it is convenient because salts with the same sign and salts with the opposite sign can be obtained alternately.

The optically active mandelic acid salt of PTE obtained in this way is recrystallized, if necessary, using the same solvent as the solvent used for crystallization, and then treated with a base such as sodium hydroxide or ammonia. When the salt is decomposed, extracted with an organic solvent such as ether or benzene, and then distilled, optically pure (+)
Or (-) PTE can be obtained.

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

Example 1 (f3PTE6.97t((α)589 = -6,4°
(~1.35゜methanol)) and (-) MA
5.02? , water: methanol = 1 = 1 mixed solvent 2
00d, and after heating and dissolving, the mixture was cooled to room temperature. This solution was inoculated with (-)PTE・(-)M A salt at 0.11F, and after being left overnight, the precipitated crystals were separated by P, and 4.429-
(-)PTE·(-)MA salt was obtained. mp=
148~152C1 [α), 35=-234,8°(
C=1.10. methanol). This (-)PTE・(-
) Add 60ml of 6N sodium hydroxide aqueous solution to MA salt.
In addition, the salt was decomposed, extracted with ether, and then distilled to obtain (-)PTE 2.569-. [α]589-
-6. ．． 0.2° (C=1.19.methanol), optical purity 96.9%.

The mother liquor from which the salt crystals were separated was evaporated under reduced pressure to solidify, leaving a solid of 7.30 fl. Add isopropyl alcohol 146 to this, heat to dissolve and cool to room temperature, then (+) P T E · (-) MA salt 0.055
' was inoculated and left overnight. By separating the precipitated crystals, (+) P T Ii:・(-) MA salt 3.6
9? I got it.

1rLP=175~177C1 [α) =+60.6
(C=1.01°35 methanol). The (+)PTE/(-)MA salt was decomposed with 60 ml of a 2N aqueous solution, extracted with ether, and then distilled to produce #)(+)PTE2.1.
I got 0F.

2 [α]58. =+58.7° (c=105.methanol), optical purity 94.5°.

Example 2 (PTE 13.01 fI- and (+)MA 9
．． 37? A mixed solvent of water: methanol = 1:1 660
- In addition, the mixture was heated and dissolved and then cooled to room temperature. Add this solution (
+)PTE/(+)MA salt approximately 61n9 was inoculated, and after being left for 2 days, the crystals were separated by P and Z51? (+) P T
E.(+)MA salt was obtained.

m, p=148-150t:', [α]=+237.8
6Cc=35 0.980. methanol). This (+)PTE・(+
) MA salt was decomposed with 45 N aqueous sodium hydroxide solution, extracted with ether, and distilled to obtain J(+)PT.
I got E3.99. [α]589=+60.2°(c
= 1.31° methanol), optical purity 96.9%.

The mother liquor from which the salt crystals were separated was evaporated to dryness under reduced pressure, leaving 14.13&- of solids. 280 g of inpropyl alcohol was added to this, heated to dissolve, cooled to room temperature, inoculated with about 6~ of (-)PTE・(+)MA salt, left to stand overnight, and precipitated crystals were separated by P. 8.26
) was obtained. [α
ζ=-614° (C=1.13.methanol). this(
-)PTE.(+)MA salt was decomposed with 5 [1 m/ml] of a 6N aqueous sodium hydroxide solution, extracted with ether, and then distilled to obtain 4.68P of Kyofi (-)PTE7. [α″JS8.= −59,4a(
C=1.20, methanol), optical purity 95.7
blood.

Example 6 In Example 2, when the (-)PTE/(+)MA salt is separated from P and the remaining mother liquor is evaporated to dryness under reduced pressure, the result is 6.14? of residual solid was obtained. In this solid (f) PTE 6.43
t, (+)MA 4.63? and water: methanol-
250M of a 1:1 mixed solvent was added, heated and dissolved, and then cooled to room temperature. Add (+)PTE・(+)M to this solution
Inoculate about 6 cm of A salt, leave it for one night, separate the crystals from P, 5.3
A crude (+) PTE·(+)MA salt of 7y- was obtained.

[α)28=+235.4° (C-35 1,03, methanol). This coarse (+) P T E・
(+) Purify M A salt by recrystallizing it twice from a mixed solvent of water: methanol = 1:1 (+) P T
E.(+)MA salt 3.695' was obtained. mp=15
0~152C1 [α)435 = ” ” 4”4゜(
C=1.03. methanol).

This purified (+)PTE・(+)MA salt 105? 1
By decomposing with 20mj of specified sodium hydroxide aqueous solution, extracting with ether, and distilling! ri(+)PTE O,
519- was obtained. (αl,,,, = +62.1°
(C=1.09, yl tanol), optical purity 100 chi.

The mother liquor from which the crude (+)PTE/(+)MA salt was separated from P was evaporated to dryness under reduced pressure, leaving a solid of 10.5551-. Add isopropyl alcohol 195- to this, heat to dissolve and cool to room temperature, then (-)PTE・(+1M
After inoculating about 6 μm of A salt and incubating for one night, the crystals were separated,
(-)PTE.(+)MA salt 6.321i1' was obtained.

[α] = 35 -61.0° (=0.984.methanol).

5.30g of this crude (-)PTE/(+)MA salt was recrystallized from 100M isopropyl alcohol, and 4.35g
- Separate #(-)PTE-(+1MA salt was obtained. mp=1
77-179c, 3 [(IE)435=-67,1°(c=tcJ 5
, meta, t-ru).

This purified (-)PTIli:・(+)M A salt was added to a 2N aqueous sodium hydroxide solution at 35+nA! (-) PTE 2
．． 36? I got it.

1 [α)58. = -61,6° (e=1.21.methanol), optical purity 992%.

Claims (1)

[Claims] Optical properties of (±)-phenyl-2-(para-tolyl)ethylamine, which is characterized by allowing optically active mandelic acid to act as a resolving agent on (±)-1-phenyl-2-(para-tolyl)ethylamine. Min Jfl-method.