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Method for realizing asymmetric alpha-hydroxylation of pyrazolone compounds through phase-transfer catalyzed photosensitized molecular oxygen

A technology of phase transfer catalysis and phase transfer catalyst, applied in organic chemistry and other directions, to achieve mild reaction conditions, good substrate applicability, environmental friendliness, and simple operation.

Active Publication Date: 2022-01-21
XINXIANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The applicant combined the strategy of phase transfer catalysis with the strategy of photo-sensitized oxidation of molecular oxygen, and successfully realized the method of preparing chiral α-hydroxylation products of pyrazolone by photo-sensitized molecular oxygen of phase-transfer catalysis. There is no related report on this aspect so far.

Method used

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  • Method for realizing asymmetric alpha-hydroxylation of pyrazolone compounds through phase-transfer catalyzed photosensitized molecular oxygen
  • Method for realizing asymmetric alpha-hydroxylation of pyrazolone compounds through phase-transfer catalyzed photosensitized molecular oxygen
  • Method for realizing asymmetric alpha-hydroxylation of pyrazolone compounds through phase-transfer catalyzed photosensitized molecular oxygen

Examples

Experimental program
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Effect test

Embodiment 1

[0019] Embodiment 1: Preparation of Ia-1

[0020]

[0021] Add NaH (60% mass fraction, 8.4g) into a 250mL three-necked flask, connect the reflux device, and connect with argon protection. At room temperature, 17.6 ml of dimethyl carbonate and 30 ml of ultra-dry tetrahydrofuran were added to the system. Heat the system to reflux. Subsequently, 10ml of acetophenone was carefully added dropwise to the system, and bubbles were released. The dropwise addition was completed in half an hour, and the stirring reaction was continued for 2 hours until no acetophenone remained as detected by TLC. After the reaction, the temperature was lowered, and 20 ml of saturated ammonium chloride was carefully added to the system under an ice bath, and the pH was adjusted to 6-7 with 3 mol / L hydrochloric acid. Then add ethyl acetate to separate the layers, the aqueous layer was extracted once with ethyl acetate, the organic layers were combined, washed once with water, washed once with saturat...

Embodiment 37

[0030]

[0031] Take a 10mL single-port reaction flask, add 0.0324g (0.1mmol) pyrazolone substrate Ia-1, 0.0001g (tetraphenylporphyrin (TPP), and 0.0028g phase transfer catalyst IIa-1 respectively. At 15°C, Add 2 mL of toluene and stir for 10 minutes. Subsequently, add 0.2 mL of 30% K 2 CO 3 Aqueous solution, react under the irradiation of 3W LED white light. After 2 hours of reaction, TLC (thin layer chromatography) traced that the reaction was almost complete. The product was separated by petroleum ether / ethyl acetate=5:1 column chromatography with a yield of 89%. Chiral HPLC (high performance liquid chromatography) analysis, the final measured ee value was 15%. Chiral OJ-H column (250×4.6mm); mobile phase: n-hexane:isopropanol=9:1; flow rate 0.8mL / min; column temperature: 25°C; detection wavelength: 254nm. τ R (major)=12.6min,τ R (minor) = 10.7min. 1 H NMR (400MHz, Chloroform-d) δ8.18–8.05(m,2H),7.67–7.55(m,2H),7.50(dd,J=5.3,2.0Hz,3H),7.31(t,J=8.0 Hz, 2H), 7.16(s...

Embodiment 136

[0098] Example 136: Preparation of (S)-pyrazolone chiral hydroxylation product Ib-1 (catalyst recycling)

[0099]

[0100]Weigh 5mmol pyrazolone Ia-1, add 2.5mol% phase transfer catalyst IIe-2, 0.005mmol TPP (porphyrin), put it into a 250mL reaction bottle, add 10% KOH aqueous solution 30mL, 100mL toluene, under 25W LED white light The reaction was stirred at -20 °C under irradiation. After reacting for 6 hours, the mixture was separated into layers, and the catalyst was slightly soluble in the organic layer and suspended in the water layer. The organic layer was collected, and the organic solvent was spin-dried, separated by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the asymmetric hydroxylated product Ib-1, and the ee was detected and the yield was calculated. Add 5 mmol of pyrazolone Ia-1, 0.005 mmol of TPP (porphyrin), and 100 mL of toluene to the water layer again, and continue stirring to react. After the reaction was finished, it was tre...

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Abstract

The invention discloses a method for realizing asymmetric alpha-hydroxylation of pyrazolone compounds by phase-transfer catalyzed photosensitized molecular oxygen, and belongs to the technical field of synthesis of chiral alpha-hydroxypyrazolone compounds in organic synthesis. According to the technical scheme, the preparation method is characterized by comprising the following steps: uniformly stirring and mixing the pyrazolone compounds, a phase transfer catalyst and a photosensitizer in a solvent, then adding alkali, and reacting at -78-60 DEG C under the condition of visible light and air or oxygen to prepare the chiral alpha-hydroxy pyrazolone compound. The method is mild in reaction condition, simple to operate, good in substrate applicability and environmental friendliness, low in cost and suitable for large-scale production.

Description

technical field [0001] The invention belongs to the technical field of synthesis of chiral α-hydroxypyrazolone compounds in organic synthesis, and in particular relates to a method for realizing asymmetric α-hydroxylation of pyrazolone compounds by phase-transfer catalyzed photosensitized molecular oxygen. Background technique [0002] Pyrazolone is a five-membered heterocyclic compound containing two nitrogen atoms, which is the core structure of many natural products and biologically active compounds. In particular, pyrazol-5-one compounds, which have insecticidal, antibacterial, analgesic, anti-inflammatory, anti-tumor effects, have been found to have an inhibitory effect on CD80, and have a strong inhibitory effect on the accumulation of protease-resistant prion proteins It can also act as a cytokine, p38 kinase inhibitor, neuroprotective agent, HIV-1 integrase inhibitor and antipyretic drug, etc. (Progressin Chemistry, 2020, 32, 1710). At the same time, compounds conta...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/22C07D231/28
CPCC07D231/22C07D231/28
Inventor 王亚坤张涛王帅飞刘洁房立真陈依帆张聪慧赵婷
Owner XINXIANG MEDICAL UNIV
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