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Synthesis method of polysubstituted 4-phenyl chroman compounds

A synthesis method, phenyl color technology, applied in the direction of organic chemistry, can solve the problems of using noble metal catalysts, harsh synthesis conditions, etc., to achieve excellent diastereoselectivity, convenient post-processing, yield and diastereoselectivity maintenance Effect

Active Publication Date: 2019-12-20
QINGDAO UNIV OF SCI & TECH
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

[0005] The object of the present invention is to provide a non-metallic catalyzed, mild multi-substituted 4-phenylchroman compound in order to overcome the existing defects of using noble metal catalysts and harsh synthesis conditions in the existing methods for preparing multi-substituted 4-phenylchromans. Preparation method of gechroman compounds

Method used

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  • Synthesis method of polysubstituted 4-phenyl chroman compounds
  • Synthesis method of polysubstituted 4-phenyl chroman compounds
  • Synthesis method of polysubstituted 4-phenyl chroman compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] The reaction equation is as follows:

[0026]

[0027] Add compound 1a (100mmol) and compound 2a (150mmol) into the reactor, add 1000mL 1,2-dichloroethane solution, then add 1,8-diazabicyclo[5.4.0]undec-7- Alkene (150mmol), while adding Molecular sieves (50m%), stirred at room temperature for 40 hours. After the reaction, the reaction system was distilled off under reduced pressure to remove 1,2-dichloroethane to obtain a crude product. The crude product was added to a silica gel chromatography column, using a mixed solvent of petroleum ether / ethyl acetate (V / V=30 / 1) as the eluent, and column chromatography gave 3a as a white solid. The yield of 3a was 85%, and the diastereoselectivity was greater than 20:1.

[0028] The NMR data of 3a are as follows:

[0029] 1 H NMR (500MHz, CDCl 3 )δ(ppm): 7.46(d, J=7.1Hz, 2H), 7.32-7.38(m, 3H), 7.16(t, J=7.2Hz, 1H), 6.96(d, J=7.8Hz, 3H) ,6.82(m,2H),5.23(d,J=6.9Hz,1H),5.14(s,1H),4.49-4.54(m,2H),3.35(s,3H),1.39(s,18H).

[...

Embodiment 2

[0032] The reaction equation is as follows:

[0033]

[0034] Add compound 1b (0.1mmol) and compound 2a (0.15mmol) into the reactor, add 1mL 1,2-dichloroethane solution, and then add 1,8-diazabicyclo[5.4.0]undeca- 7-ene (0.15mmol), while adding Molecular sieves (50m%), stirred at room temperature for 40 hours. After the reaction, the reaction system was distilled off under reduced pressure to remove 1,2-dichloroethane to obtain a crude product. The crude product was added to a silica gel chromatography column, using a mixed solvent of petroleum ether / ethyl acetate (V / V=30 / 1) as the eluent, and column chromatography gave 3b as a white solid. The yield of 3b was 80%, and the diastereoselectivity was greater than 20:1.

[0035] The NMR data of 3b are as follows:

[0036] 1 H NMR (500MHz, CDCl 3 )δ (ppm): 7.45 (d, J = 7.2Hz, 2H), 7.30-7.37 (m, 3H), 6.94 (s, 2H), 6.89 (d, J = 8.8Hz, 1H), 6.74 (dd, J=8.8,2.5Hz,1H),6.36(d,J=2.5Hz,1H),5.16(d,J=8.4Hz,1H),5.12(s,1H),4.46-4.52...

Embodiment 3

[0039] The reaction equation is as follows:

[0040]

[0041] Add compound 1a (0.1mmol) and compound 2b (0.15mmol) into the reactor, add 1mL 1,2-dichloroethane solution, then add 1,8-diazabicyclo[5.4.0]undeca- 7-ene (0.15mmol), while adding Molecular sieves (50m%), stirred at room temperature for 40 hours. After the reaction, the reaction system was distilled off under reduced pressure to remove 1,2-dichloroethane to obtain a crude product. The crude product was added to a silica gel chromatography column, using a mixed solvent of petroleum ether / ethyl acetate (V / V=30 / 1) as the eluent, and column chromatography gave 3c as a white solid. The yield of 3c was 56% with a diastereoselectivity greater than 20:1.

[0042] The NMR data of 3c are as follows:

[0043] 1 H NMR (500MHz, CDCl 3 )δ(ppm): 7.32(d, J=4.6Hz, 1H), 7.16(t, J=7.3Hz, 1H), 7.08(d, J=2.2Hz, 1H), 6.93-6.97(m, 4H) ,6.80-6.86(m,2H),5.58(d,J=9.9Hz,1H),5.15(s,1H),4.42-4.53(m,2H),3.43(s,3H),1.39(s,18H ).

[004...

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Abstract

The invention belongs to the technical field of organic synthesis and discloses a synthesis method of polysubstituted 4-phenyl chroman compounds. The structural formula of polysubstituted 4-phenyl chroman compounds is shown by formula I. The method involves non-metal catalyzed oxamichael addition and 1,6-tandem reaction conjugated addition under mild condition. The catalyst used in the invention is a commercial nonmetallic alkali, has low cost, is environmentally friendly and is easy to operate; the method disclosed in the invention has high yield, excellent diastereoselectivity, mild conditions, convenient post-treatment and easy separation and purification of products; the method of the invention is easy to produce on a large scale, and the amplified yield and diastereoselectivity can bemaintained.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and mainly relates to a synthesis method of multi-substituted 4-phenylchroman compounds. Background technique [0002] 4-Phenylchromans are widely found in bioactive molecules and natural products, such as: omexifen, a selective estrogen receptor modulator; and MyristininA, a Flavonoids extracted from fenugreek have antifungal activity. [0003] Because 4-phenylchroman compounds have potential medicinal value and wide application, the synthesis and reporting of such compounds is a long-term research direction of chemists, which is of great significance. At present, the strategies for synthesizing such compounds mainly fall into the following two categories: oxadiene synthesis reactions (Angew.Chem., Int.Ed.2015, 54, 5460-5464; Org.Biomol.Chem. 7276.) and the [4+2] cycloaddition reaction of o-hydroxyphenyl-p-methylenebenzoquinone (p-QMs) with alkenes (Angew.Chem., Int.Ed.2016,55,12104-12108 ; J...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/60C07D409/04
CPCC07D311/60C07D409/04
Inventor 吕健宋然司雯
Owner QINGDAO UNIV OF SCI & TECH
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