CN102199130A

CN102199130A - Preparation and synthesis method for chiral oxazoline

Info

Publication number: CN102199130A
Application number: CN201110069671XA
Authority: CN
Inventors: 罗梅
Original assignee: Individual
Current assignee: Individual
Priority date: 2011-03-22
Filing date: 2011-03-22
Publication date: 2011-09-28

Abstract

The invention discloses a preparation and synthesis method for chiral oxazoline. The chiral oxazoline is 1-[2-4-isobutyl-4,5-dihydro-2-oxazolinyl]-ethyl hexahydropyridine, which has the chemical structural formula shown as the description. The synthesis method for the chiral oxazoline comprises reaction, separation and purification, and is characterized by comprising the following steps of: performing reflux reaction on 3-(1-hexahydropyridine)-propionitrile and D-leucinol in a chlorobenzene solvent for 24 hours in the presence of a catalyst of anhydrous ZnCl2 under the conditions of no water and no oxygen; and separating and purifying, namely removing the chlorobenzene after the reaction is finished, adding water to dissolving the product, extracting by using chloroform, removing a solvent from an extract phase, and purifying through column chromatography. The chiral oxazoline serving as a chiral catalyst in the process of preparing a chiral target product from 2-methylbenzaldehyde through Henry reaction has good catalytic effect.

Description

A kind of preparation of chiral oxazoline and synthetic method

One, technical field

The present invention relates to a kind of chipal compounds and purposes, specifically preparation of a kind of chiral oxazoline and uses thereof.

Two, background technology

The title complex of chiral oxazoline and metal (shows the active and high enantioselectivity of good asymmetry catalysis, thereby is subjected to paying close attention to widely at Didls-Alder in the many reactions such as diene cycloaddition reaction, Michael (Mi Xieer) condensation reaction, Friedel-Crafts (Fu Ruide-carat Buddhist now) condensation reaction, Aldol (alcohol aldehyde) condensation reaction of Di Lesi-Ai Erte).

Three, summary of the invention

The present invention is intended to provide a kind of efficient chiral catalyst for the asymmetric synthesis field particularly prepares the chiral drug compound, technical problem to be solved be select and the synthesis of chiral part with the preparation composition catalyst.

The alleged chiral oxazoline of the present invention is that chemical name is 1-[2-4 (R)-isobutyl--4,5-dihydro-2-oxazolinyl]-ethyl piperidine, be the compound (I) shown in the following chemical formula (I):

This chiral oxazoline compound (I) has shown catalytic effect preferably at the Henle reaction of 2-tolyl aldehyde.

The synthetic method of this chipal compounds is a feedstock production compound 1-[2-4-isobutyl--4 with 3-(1-hexahydropyridine base)-propionitrile, 5-dihydro-2-oxazolinyl]-ethyl piperidine, flow process schematically as follows:

The synthetic method of this chiral oxazoline comprises reaction, separation and purifying, it is characterized in that by 3-(1-hexahydropyridine base)-propionitrile and D-leucinol under the anhydrous and oxygen-free condition and the anhydrous ZnCl of catalyzer ₂When existing in chlorobenzene solvent back flow reaction 24 hours, separate then, purifying, i.e. reaction is sloughed chlorobenzene after finishing, chloroform extraction is used in the back that is dissolved in water, and uses column chromatography purification behind the extraction phase precipitation.

Four, description of drawings

Fig. 1, Fig. 2 are respectively the chiral oxazoline Compound I ¹HNMR figure and ¹³CNMR figure.

Five, embodiment

(the preparation of a) chiral oxazoline Compound I

In the 100mL two-mouth bottle, under the anhydrous and oxygen-free condition, add anhydrous ZnCl ₂2g (14.7mmol), the 40mL chlorobenzene, 3-(1-hexahydropyridine base)-propionitrile 6.3g, D-leucinol 10g, with the mixture 24h that at high temperature refluxes, stopped reaction, decompression is desolvated to remove,,, and use CHCl with the residuum water dissolution ₃(20mLx2) extraction, the organic phase anhydrous sodium sulfate drying, rotation removes and desolvates, and thick product with sherwood oil/methylene dichloride (4: 1) column chromatography, is got colourless oil liquid productive rate 70%; [a] ⁵ _D=+30.40 ° of (c=0.148, CHCl ₃): ¹HNMR (500MHz, CDCl ₃, 27 ℃), δ (ppm)=4.26～4.30 (m, 1H), 4.07～4.11 (m, 1H), 3.77～3.79 (m, 1H), 2.64～2.68 (m, 1H), 2.41～2.48 (m, 4H), 1.40～1.60 (m, 8H), 1.23～1.25 (m, 2H), 0.91～0.95 (m, 6H) ¹³CNMR, 22.68,22.77,24.28,25.35,25.93,26.07,45.61,53.72,54.19,54.93,55.34,64.52,72.74,166.04.IR (KBr compressing tablet): 3307,2934,2869,2804,1668,1545,1468,1384,1367,1304,1273,1225,1172,1156,1116,1040,989,920,862,758, HRMS (EI): m/z (%): calcd for C ₁₄H ₂₆N ₂O:238.2045; Found:238.2038.

(2) 2-nitro-1-(2 '-phenyl) alcoholic acid preparation

Get 0.20mmol chiral oxazoline compound 1 (catalytic amount is 20%) in the little flask of 25mL, the methanol solution that adds 2 milliliters, then, add the 2-tolyl aldehyde of 0.1mmol and the Nitromethane 99Min. of 0.5mL in above-mentioned solution, stirring at normal temperature was reacted 72 hours, with sherwood oil/eluent methylene chloride, carry out column chromatography, transformation efficiency: 67% ¹HNMR (300MHz, CDCl ₃) 7.28～7.32 (m, 5H, Ar-H), 5.32～5.35 (d, J=9.18Hz, 1H ,-CH), 4.38～4.56 (m, 2H ,-CH ₂), 3.89 (br, 1H ,-OH).

Claims

1. chiral oxazoline is characterized in that: by following chemical formulation, its chemical name is 1-[2-4-isobutyl--4,5-dihydro-2-oxazolinyl]-ethyl piperidine, following chemical structural formula is arranged:

2. the synthetic method by the described chiral oxazoline of claim 1 comprises reaction, separation and purifying, it is characterized in that by 3-(1-hexahydropyridine base)-propionitrile and D-leucinol under the anhydrous and oxygen-free condition and the anhydrous ZnCl of catalyzer ₂When existing in chlorobenzene solvent back flow reaction 24 hours, separate then, purifying, i.e. reaction is sloughed chlorobenzene after finishing, chloroform extraction is used in the back that is dissolved in water, and uses column chromatography purification behind the extraction phase precipitation, catalyst levels is 1～3wt% of material quantity.