Method for synthesizing chiral amine compound through catalyzing asymmetric hydrogenated imine by using iridium

A technology of hydrogenated imines and synthetic methods, applied in asymmetric synthesis, preparation of organic compounds, organic chemical methods, etc., can solve problems such as high equipment requirements, difficult ligand synthesis, etc., and achieve high selectivity

Inactive Publication Date: 2019-03-05
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the synthesis of ligands used in this reaction is difficult, and a large amount of acid is used in the hydrogenation system, which requires high equipment requirements.

Method used

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  • Method for synthesizing chiral amine compound through catalyzing asymmetric hydrogenated imine by using iridium
  • Method for synthesizing chiral amine compound through catalyzing asymmetric hydrogenated imine by using iridium
  • Method for synthesizing chiral amine compound through catalyzing asymmetric hydrogenated imine by using iridium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] 1 Preparation of Ligand I a

[0036] At minus 20 degrees, add n-butyllithium (0.1mol) dropwise to the ether solution of 12.118g of α-phenylethylamine, and then stir for 30min, then add trimethylchlorosilane (0.1mol), and stir for 30min Then add n-butyllithium (0.13mol) dropwise, and stir for 1h; then add diphenylphosphorous chloride (0.11mol) dropwise therein, stir for 2h after adding, rise to room temperature and stir for 4h, and then use 10% HCl (aq) Quench the reaction, separate the layers, spin the organic layer to dryness, and recrystallize with n-hexane to obtain a white solid (abbreviated as DPPNH 2 ), yield 48%.

[0037] To 3.0535g DPPNH 2 Add 2.5050 g of diphenylphosphine chloride to the toluene solution of (1 equiv) under the condition of 5 ml of triethylamine. After the reaction is finished, the salt generated by the reaction is filtered off, the organic phase is spin-dried, and recrystallized with n-hexane to obtain the ligand I a , yield 95%.

[0038] ...

Embodiment 2

[0057] The hydrogenation reaction was carried out in a 200ml autoclave. First the reactor was replaced with nitrogen three times, then 52g of imine (generated by 2-methyl-6-ethylaniline and methoxyacetone) was injected into the reactor, and then 0.5ml of in-situ coordinated catalyst ( S / C=5×10 5 ). Replace with hydrogen three times, pressurize to 80bar with hydrogen, heat up to 100°C for 3h, cool down, release the pressure, open the kettle, GC analysis reaction conversion rate is greater than 99%, vacuum distillation to get 50g (S)-NAA, yield 95%, HPLC analysis ee value is 91%.

[0058] The structural formula of (S)-NAA is as follows:

[0059]

[0060] HPLC (OJ-H, n-hexane / i-PrOH=98 / 2, 1.0ml / min, 254nm, 40°C):t R (minor)=3.9min,t R (major) = 4.3min. 1 H NMR (400MHz, CDCl 3 ):7.02(dd,J=7.6,15.2Hz,2H),6.89(t,J=7.6Hz,1H),3.36-3.40(m,6H),2.67(q,J=7.6Hz,2H),2.31 (s, 3H), 1.25 (t, J = 7.6Hz, 3H), δ = 1.20 (d, J = 5.6Hz, 3H) ppm.

Embodiment 3

[0062] Other conditions are the same as in Example 2, the reaction pressure is 100 bar, the GC analysis reaction conversion rate is greater than 99%, and the HPLC analysis ee value is 90%.

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Abstract

The invention relates to a method for synthesizing a chiral amine compound through catalyzing high-activity high-selectivity asymmetric hydrogenated imine by using iridium. An adopted catalyst is generated in situ by an iridium-cyclooctadiene complex and a chiral phosphine-amino phosphine ligand. (S)-N-(1-methoxy-2-propyl)-2-methyl-6-ethylaniline [(S)-NAA] can be obtained by catalyzing a hydrogenation reaction of 2-methyl-6-ethyl-N-methylene aniline (EMA-imine) by using the catalyst, wherein the enantiomeric excess (ee) can reach 90%, and the molar ratio of the EMA-imine to the catalyst can beup to 1000000. Refined metolachlor with an S-configuration effective content of 94% can be obtained by carrying out an acylation reaction on the (S)-NAA with chloroacetyl chloride. Therefore, the ligand provided by the invention can be used for synthesizing the chiral herbicide metolachlor.

Description

technical field [0001] The invention belongs to the technical field of chiral pesticide production. The invention provides a method for synthesizing chiral amine compounds through iridium-catalyzed high-activity and high-selectivity asymmetric hydrogenation of imines, which is suitable for the production of herbicide metolachlor-pure intermediates and metalaxyl-pure intermediates. Background technique [0002] Chiral amine compounds are important intermediates in organic synthesis and can be used to prepare various natural and non-natural compounds with biological activity. In recent years, the preparation of chiral amine compounds by asymmetric catalytic hydrogenation of imines has achieved great success [(a) H.-U. Blaser, F. Spinder in Handbook of Homogeneous Hydrogenation (Eds.: J.G.de Vries, C.J. Elsevier), Wiley-VCH, Weinheim, 2007, pp.1193; (b) C.Claver, E.Fernandez in Morden Reduction Methods (Eds.: P.Anderson, I.Munslow), Wiley-VCH, Weinheim, 2008, pp.237; (c) H.-U...

Claims

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Application Information

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IPC IPC(8): C07B53/00C07C213/02C07C217/08C07C227/06C07C229/18C07C231/02C07C233/18B01J31/24
CPCB01J31/2495B01J2231/643B01J2531/0238B01J2531/827C07B53/00C07B2200/07C07C213/02C07C227/06C07C231/02C07C217/08C07C229/18C07C233/18
Inventor 胡向平胡信虎
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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