Preparation method of alpha-hydroxy-beta-dicarbonyl compound using cinchona alkaloid derivative as catalyst

A technology of dicarbonyl compounds and cinchona base, which is applied in the preparation of organic compounds, chemical instruments and methods, and preparation of carboxylate esters, and can solve problems such as inapplicable production

Inactive Publication Date: 2013-10-02
DALIAN UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] CN101503358, Synlett.2009,16,2659-2662 discloses that the analgesic diterpene alkaloid homogenin catalyzes the asymmetric oxidation reaction of β-dicarbonyl compounds, the ...

Method used

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  • Preparation method of alpha-hydroxy-beta-dicarbonyl compound using cinchona alkaloid derivative as catalyst
  • Preparation method of alpha-hydroxy-beta-dicarbonyl compound using cinchona alkaloid derivative as catalyst
  • Preparation method of alpha-hydroxy-beta-dicarbonyl compound using cinchona alkaloid derivative as catalyst

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Embodiment 1: prepare 9-oxygen-benzyl-6'-hydroxy cinchonidine (formula IIIa, wherein R 10 , R 11 for H).

[0086] Quinine (648 mg, 2.0 mmol) was dissolved in 20 ml of DMF, and 300 mg of 40% mass fraction of sodium hydride was added under nitrogen protection. After the mixture was stirred at room temperature for 1 hour, Bian bromide (423 mg, 2.5 mmol) was mixed with 2 ml of DMF, carefully added dropwise into the reactor, and stirred overnight at room temperature. After the raw materials were completely reacted, brine was added to quench the system, and the mixture was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and evaporated in vacuo. The crude product was a yellow oil, which was directly used in the next reaction. Add 1.2 g of 40% mass fraction of sodium hydride to the dry DMF, and carefully add 2 ml of ethanethiol with a needle under the protection of nitrogen. After the reaction mixture was stirred for two...

Embodiment 2

[0087] Embodiment 2: 9-O-(3,5-tert-butyl)-benzyl-6'-hydroxy cinchonidine (formula IIIa, wherein R 10 is tert-butyl, R 11 for H)

[0088] With the preparation method of Example 1, silica gel column chromatography (elution gradient: CH 2 Cl 2 / MeOH / Et 3 N=100:5:1), a white solid was obtained with a final yield of 82%. [α] D 20 =-51.6(c0.25, CHCl 3 );mp:108-110℃; 1 H NMR (400MHz, CDCl 3 )δ8.69(d,J=4.4Hz,1H),8.02(d,J=9.0Hz,2H),7.47(d,J=3.9Hz,1H),7.37(s,1H),7.31(d, J=8.9Hz,1H),7.17(s,2H),5.74–5.52(m,2H),5.07–4.77(m,2H),4.47(s,3H),3.77(s,1H),3.25(t ,J=12.0Hz,1H),3.10(s,1H),2.90(d,J=7.3Hz,1H),2.69(d,J=10.5Hz,1H), 2.42(s,1H),2.13(s ,1H),2.00(s,1H),1.89(s,1H),1.65(s,1H),1.49(d,J=7.0Hz,1H),1.43–1.21(m,18H). 13 C NMR (101MHz, CDCl 3 )δ150.90,146.78,143.78,140.53,138.35,136.90,131.32,127.95,123.00,121.81,121.73,115.13,107.23,104.75,71.87,59.66,56.27,39.35,34.85,31.47,27.80,26.77.HRMS(ES + ) calcd for (C 34 h 44 N 2 o 2 +H + ):513.3405,found:513.3412.

Embodiment 3

[0089] Embodiment 3: prepare 9-O-(3-trifluoromethyl)-benzyl-6'-hydroxy cinchonidine (formula IIIa, wherein R 10 is trifluoromethyl, R 11 for H)

[0090] With the preparation method of Example 1, silica gel column chromatography (elution gradient: CH 2 Cl 2 / MeOH=15:1), a white solid was obtained with a final yield of 81%. [α] D 20 =-31.5(c0.25, CHCl 3 );mp:117-121℃; 1 H NMR (400MHz, CDCl 3 )δ8.71(d,J=4.2Hz,1H),8.12(s,1H),8.03(d,J=9.0Hz,1H),7.63(d,J=7.8Hz,2H),7.46(d, J=8.5Hz,3H),7.34(d,J=8.7Hz,1H),5.73(s,1H),5.68–5.53(m,1H),5.05–4.84(m,2H),4.49(dd,J =26.8,11.8Hz,2H),3.71(s,1H),3.39–3.12(m,2H),2.92(d,J=28.5Hz,1H),2.78(d,J=11.8Hz,1H),2.45 (s,1H),2.11(s,1H),1.93(s,2H),1.61(d,J=47.4Hz,2H). 13 C NMR (101MHz, CDCl 3 )δ156.89,146.71,143.91,142.51,139.90,138.66,131.61,131.08,130.60,129.02,127.65,125.41,124.63,123.95,123.16,115.61,106.27,77.35,77.03,76.72,70.51,59.58,56.00,45.35,43.51 , 38.91, 27.57, 26.43. HRMS (ES + ) calcd for (C 27 h 27 f 3 N 2 o 2 +H + ):469.203...

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Abstract

The invention discloses a preparation method of an alpha-hydroxy-beta-dicarbonyl compound using a cinchona alkaloid derivative as a catalyst. In the condition that the cinchona alkaloid derivative is used as the catalyst, a compound is caused to be in contact with oxidants including oxygen, hydrogen peroxide, and alkyl hydroperoxide; the compound and the oxidant in contact are mixed and stirred in an inert solvent for reaction; after the reaction is ended, the alpha-hydroxy-beta-dicarbonyl compound is obtained by separation, wherein the inert solvent comprises halogenated hydrocarbon, aromatic hydrocarbon, alkane and the like; the dosage molar ratio of the peroxide, which is used as the oxidant, to a beta-dicarbonyl compound is 1-30; the dosage of the catalyst III is 0.5-50mol%; the reaction temperature is minus 78 to 50 DEG C. According to the novel preparation method of the alpha-hydroxy-beta-dicarbonyl compound using the cinchona alkaloid derivative as the catalyst disclosed by the invention, cinchona alkaloid quinine and cinchona alkaloid quinindium, which are main alkaloids in the bark of cinchona and congener, are widely applied to organic unsymmetrical catalytic reaction.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis and relates to a method for preparing chiral α-hydroxyl-β-dicarbonyl compounds using cinchona base derivatives as catalysts. technical background [0002] The optically active α-hydroxy-β-dicarbonyl structure is ubiquitous in natural products and some drug molecules and pesticide molecular structures; some α-hydroxy-β-dicarbonyl compounds can be used as intermediates to prepare fine chemicals, drugs and plants Protective products such as oxadiazines. The most direct and effective way to synthesize chiral α-hydroxy-β-dicarbonyl compounds is chiral catalytic oxidation of β-dicarbonyl compounds. [0003] In recent years, some methods for the preparation of α-hydroxy-β-dicarbonyl compounds have been reported. WO95 / 29171 reports a preparation method for the preparation of oxadiazines and hydroxylation of β-dicarbonyl compounds, including a preparation step involving the hydroxylation of β-k...

Claims

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Application Information

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IPC IPC(8): C07C69/757C07C67/31
Inventor 孟庆伟王亚坤李智廉明明姚鸿杰曾辉
Owner DALIAN UNIV OF TECH
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