CN1066434C - Resolution of (minus and plus) -1-arylethanamine - Google Patents
Resolution of (minus and plus) -1-arylethanamine Download PDFInfo
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- CN1066434C CN1066434C CN97110696A CN97110696A CN1066434C CN 1066434 C CN1066434 C CN 1066434C CN 97110696 A CN97110696 A CN 97110696A CN 97110696 A CN97110696 A CN 97110696A CN 1066434 C CN1066434 C CN 1066434C
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- China
- Prior art keywords
- alpha
- ben yian
- aromatic
- ethamine
- yian
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Abstract
The present invention belongs to a disassemble technology for (+/-)-1-aryl ethylamine, which adopts a synthetic method of a disassemble reagent of R (-)-tetrahydrothiazole-2-thione-4-carboxylic acid which is shortened R (-)-TTCA. The synthetic method has the advantages of simplicity, facile raw materials, low cost and simple disassemble processes, and the optical purity of disassembled R (+)-alpha-aryl ethylamine and S (-)-alpha-aryl ethylamine is high.
Description
The invention belongs to (±)-the 1-aryl amine disassemble technique of (R.S-alpha-aromatic ethamine).
Have optically active α-Ben Yian, be important chirality synthetic intermediate, chiral source to methyl-α-Ben Yian, to the chloro-α-Ben Yian, to methoxyl group-α-Ben Yian, to nitro-α-Ben Yian etc.Can replace alkaloids such as ephedrine, brucine, quinine as resolution reagent again to R.S-acid.Therefore, having optically active alpha-aromatic ethamine is subjected to people and payes attention to widely.
The classical resolution process of R.S-alpha-aromatic ethamine is to split for resolution reagent with (+) or (-) tartrate, oxysuccinic acid (A.W.Ingersoll, Organic Synthesis, Coll.Vol.2, p506,1943).
Nineteen ninety, Japanese Patent (special permission, put down-2-4581) be that employing (+) amygdalic acid is that resolution reagent splits the R.S-α-Ben Yian.The shortcoming of these methods is: the resolution reagent that has is difficult to obtain, and price is more expensive; The need on fractured operation that have are recrystallization repeatedly, and process is numerous and diverse.
The present invention splits R.S-alpha-aromatic ethamine (R.S-α-Ben Yian, R.S-to methyl-α-Ben Yian, R.S-to chloro-α-Ben Yian, R.S-to methoxyl group-α-Ben Yian, R.S-to nitro-α-Ben Yian) for splitting examination with R (-)-thiazolidinethion-2-4-carboxylic acid [be called for short R (-) TTCA].The mol ratio of R (-) TTCA and the reaction of R.S-alpha-aromatic ethamine is 1: 2.Be characterized in: R (-) TTCA is that a kind of chiral reagent is used in the fractionation of R.S-alpha-aromatic ethamine first, its synthetic method simple (Chinese invention patent bulletin 1996,52,26), and raw material is easy to get, and cost is low.The optical purity of the R (+) that fractionation obtains-alpha-aromatic ethamine and S (-)-alpha-aromatic ethamine can reach 94.45%, and split process is simple.
The present invention is dissolved in organic solvent (ethyl acetate with R (-) TTCA (1mmol), chloroform, benzene, ether etc.) in, at 0 ℃～60 ℃, stir, be added drop-wise in (2mmol) R.S-alpha-aromatic ethylamine solution of corresponding organic solvent dissolution, drip the back and continued stirring reaction 30～60 minutes, generate a large amount of white precipitates, filtering out white solid is the ammonium salt of R (-) TTCAS (-)-alpha-aromatic ethamine
-44.05 °～-64.40 °, productive rate is up to 98.0%.
Filtrate is washed with 1.0M NaOH solution, and the saturated NaCl aqueous solution is washed, the organic layer anhydrous Na
2SO
4Drying steams solvent, obtains optically active R (+)-alpha-aromatic ethamine, and productive rate is up to 92.0%, and optical purity reaches 94.45%.
White solid is decomposed with 1.0M NaOH solution, use organic solvent extraction, the organic layer anhydrous Na
2SO
4Drying, decompression steams organic solvent, obtains optically active S (-)-alpha-aromatic ethamine, and productive rate reaches 85.1%, and optical purity is 90.36%.Water is neutralized to pH ≈ 1 with 1M HCl solution, and with organic solvent extraction, decompression steams organic solvent, recyclable R (-) TTCA,
-83.19～-85.50 °, the rate of recovery reaches 87.1%.
The fractionation of embodiment 1:R.S-α-Ben Yian
0.1640g (1mmol) R (-) TTCA is dissolved in (or chloroform in the ethyl acetate (10mL), benzene, ether etc.), be added drop-wise under the stirring at room in R.S-α-Ben Yian (10mL) ethyl acetate solution that is dissolved with 0.26mL (2mmol), continue reaction 30 minutes after dripping again, system produces a large amount of white precipitates, filter to such an extent that white solid is the ammonium salt of R (-) TTCAS (-)-α-Ben Yian, productive rate 92.0%, m.p.154～156 ℃
-53.14 ° (c 0.20, H
2O).
Filtrate is washed with 10mL 1M NaOH solution, and the saturated NaCl aqueous solution of 10mL is washed anhydrous Na
2SO
4Drying, decompression steams ethyl acetate, gets R (+)-α-Ben Yian, productive rate 89.0%,
+ 29.28 °, optical purity 94.45%.
White solid decomposes with 10mL 1.0M NaOH solution, with ethyl acetate (3 * 10mL) extractions, anhydrous Na
2SO
4Dry organic layer, decompression steams solvent, obtains optically active S (-)-α-Ben Yian, productive rate 80.0%,
-25.45 ° (c 0.16, C
2H
5OH), optical purity 82.10%.
Water is neutralized to pH ≈ 1 with 1M HCl liquid, with ethyl acetate (3 * 10mL) extraction, the decompression steam organic solvent, obtain R (-) TTCA,
-83.83 ° (c 0.20, and 0.5MHCl), the rate of recovery reaches 87.1%.
Embodiment 2:R.S-is to the fractionation of methoxyl group-α-Ben Yian
As embodiment 1 operation, white solid is R (-) TTCAS (-)-to methoxyl group-α-Ben Yian, productive rate 86.6%, m.p.164～166 ℃,
-47.24 ° (c 0.12, H
2O); R (+)-to methoxyl group-α-Ben Yian, productive rate 81.0%,
+ 26.02 ° (c 0.31, C
2H
5OH), optical purity 90.66%; Obtain S (-)-to methoxyl group-α-Ben Yian, productive rate 82.4%,
-24.70 (c 0.92, C
2H
5OH), optical purity 86.10% reclaims and obtains R (-) TTCA,
-83.19 °, the rate of recovery reaches 85.6%.
Embodiment 3:R.S-is to the fractionation of chloro-α-Ben Yian
As embodiment 1 operation, obtain white solid and be R (-) TTCAS (-)-to the ammonium salt of chloro-α-Ben Yian, productive rate 98.0%, m.p.172～174 ℃,
-47.62 ° of (c0.10, H
2O); Obtain R (+)-to the chloro-α-Ben Yian, productive rate 91.0%,
+ 23.34 (c0.19, C
2H
5OH), optical purity 87.19%; S (-)-to the chloro-α-Ben Yian, productive rate 85.1%,
-24.19 ° (c 0.12, C
2H
5OH), optical purity 90.36%; Reclaim R (-) TTCA,
-85.00 °, the rate of recovery reaches 86.5%.
Embodiment 4:R.S-is to the fractionation of methyl-α-Ben Yian
As embodiment 1 operation, obtain white solid and be R (-) TTCAS (-)-to the ammonium salt of methyl-α-Ben Yian, productive rate 94.5%, m.p.156～158 ℃,
-48.93 ° (c 0.17, H
2O; Obtain R (+)-to methyl-α-Ben Yian, productive rate 75.3%,
+ 21.49 (c0.24, C
2H
5OH), optical purity 74.54%; S (-)-to methyl-α-Ben Yian, productive rate 74.9%,
-21.00 ° (c 0.26, C
2H
5OH), optical purity 72.84%; Reclaim R (-) TTCA,
-83.50 °, the rate of recovery reaches 85.0%.
Embodiment 5:R.S-is to the fractionation of nitro-α-Ben Yian
As embodiment 1 operation, obtain white solid and be R (-) TTCAS (-)-to the ammonium salt of nitro-α-Ben Yian, productive rate 86.0%, m.p.168～170 ℃,
-64.40 ° (c 0.10, H
2O); Obtain R (+)-to nitro-α-Ben Yian, productive rate 74.3%,
+ 17.69 (c0.21, C
2H
5OH), optical purity 91.66%; S (-)-to nitro-α-Ben Yian, productive rate 76.6%,
-16.00 ° (c 0.12, C
2H
5OH), optical purity 82.90%; Reclaim R (-) TTCA,
-85.50 °, the rate of recovery reaches 82.5%.
Claims (1)
1. the method for splitting of a R.S-alpha-aromatic ethamine, it is characterized in that: is that R.S-α-Ben Yian or R.S-split nitro-α-Ben Yian methoxyl group-α-Ben Yian, R.S-chloro-α-Ben Yian, R.S-methyl-α-Ben Yian, R.S-with resolution reagent R (-)-thiazolidinethion-2-4-carboxylic acid to R.S-alpha-aromatic ethamine, the mol ratio of R (-)-thiazolidinethion-2-4-carboxylic acid and the reaction of R.S-alpha-aromatic ethamine is 1: 2, temperature of reaction is 0 ℃～60 ℃, and the reaction medium organic solvent is CH
3COOC
2H
5Or CHCl
3, C
6H
6, C
2H
5OC
2H
5, reacted 30～60 minutes, generate a large amount of white precipitates, to filter, filtrate is washed with 1.0MNaOH solution, and the saturated NaCl aqueous solution is washed, the organic layer anhydrous Na
2SO
4Drying, evaporating solvent obtains optically active R (+)-alpha-aromatic ethamine, and white solid uses 1.0MNaOH solution to decompose, and uses organic solvent extraction, organic layer Na
2SO
4Drying, decompression steams organic solvent, obtains optically active S (-)-alpha-aromatic ethamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97110696A CN1066434C (en) | 1997-06-09 | 1997-06-09 | Resolution of (minus and plus) -1-arylethanamine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97110696A CN1066434C (en) | 1997-06-09 | 1997-06-09 | Resolution of (minus and plus) -1-arylethanamine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1171393A CN1171393A (en) | 1998-01-28 |
| CN1066434C true CN1066434C (en) | 2001-05-30 |
Family
ID=5171543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97110696A Expired - Fee Related CN1066434C (en) | 1997-06-09 | 1997-06-09 | Resolution of (minus and plus) -1-arylethanamine |
Country Status (1)
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|---|---|
| CN (1) | CN1066434C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105153108A (en) * | 2015-08-31 | 2015-12-16 | 彭静 | Method of preparing R-3, 4-(methylenedioxy) mandelic acid by resolving |
| CN105153109A (en) * | 2015-09-02 | 2015-12-16 | 彭静 | Method for split preparation of S-3,4-(methylenedioxy) mandelic acid |
| CN108658784B (en) * | 2018-04-26 | 2020-12-18 | 联化科技股份有限公司 | Synthesis method of (R) -1- (4-methylphenyl) ethylamine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06107603A (en) * | 1992-09-30 | 1994-04-19 | Toray Ind Inc | Production of optically active 1-phenylethylamine derivative |
| JPH09143128A (en) * | 1995-11-24 | 1997-06-03 | Koei Chem Co Ltd | Production of optically active 1-phenylethylamine |
-
1997
- 1997-06-09 CN CN97110696A patent/CN1066434C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06107603A (en) * | 1992-09-30 | 1994-04-19 | Toray Ind Inc | Production of optically active 1-phenylethylamine derivative |
| JPH09143128A (en) * | 1995-11-24 | 1997-06-03 | Koei Chem Co Ltd | Production of optically active 1-phenylethylamine |
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| Publication number | Publication date |
|---|---|
| CN1171393A (en) | 1998-01-28 |
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