Method for synthesizing Stilbene compound by utilizing Pfitzner-moffatt oxidizing reaction

A technology of stilbene compounds and oxidation reaction, which is applied in the field of synthesis of stilbene compounds by Pfitzner-moffatt oxidation reaction, which can solve the problems of high toxicity, environmental damage, and difficulty in industrial production

Inactive Publication Date: 2010-09-15

HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY

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AI-Extracted Technical Summary

Problems solved by technology

[0003] In recent years, the skeletons of stilbene compounds reported in literature at home and abroad are generally realized through Wittig-Horner condensation. The condensation reaction is carried out between substituted benzyl diethyl phosphate and substituted benzaldehyde. Some complex substituted benzaldehydes are generally formed from substituted benzene Oxidative synthesis of methanol, in order to prevent the generation of substituted benzoic acid and ensure that the oxidation stays in the aldehyde stage, special oxidizing ...

Abstract

The invention discloses a method for synthesizing Stilbene compound by utilizing Pfitzner-moffatt oxidizing reaction. In the method, substituted benzyl alcohol is taken as a raw material, DMSO, namely dimethyl sulfoxide is adopted to prepare corresponding substituted benzaldehyde compound through Pfitzner-moffatt oxidizing reaction; and the target production Stilbene compound is prepared through Wittig-Horner condensation. The method is simple and practicable, has safe reactant involving in the synthesized process, moderate reaction condition and high yield, is suitable for the industrial production of various Stilbene compound, such as red sandalwood, Stilbene, resveratrol, oxidized resveratrol and Piceatannol, etc.

Application Domain

Organic compound preparationOrganic chemistry methods

Technology Topic

BenzaldehydeBENZYL ALCOHOL/WATER +6

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Examples

Experimental program(8)

Example Embodiment

[0102] Example 1 A method for synthesizing 3,5-dimethoxy-4-isopropyl stilbene, namely phenenmod by Pfitzner-moffatt oxidation reaction

[0103] The reaction route of this example is as shown in formula (II):

[0104]

[0105] The reaction process is a 1 →b 1 →c 1 , The step-by-step reaction formula is as follows:

[0106]

[0107] The method of synthesizing phenenmod by Pfitzner-moffatt oxidation reaction is carried out in the following sequence of steps:

[0108] a 1.Compound A 1 That is the preparation of 3,5-dimethoxy-4-isopropylbenzaldehyde:

[0109] Take 10.0 g (47.6 mmol) of 3,5-dimethoxy-4-isopropylbenzyl alcohol, 33 mL of DMSO, and 22.5 mL of acetic anhydride into a four-necked flask, stir, and react at room temperature with TLC monitoring. After the reaction is completed, process, add water, extract with ethyl acetate, wash with water, and remove the solvent by rotary evaporation to obtain product A 1 8.72g (41.9mmol). The yield was 88%.

[0110] b 1. Preparation of compound B1, 3,5-dimethoxy-4-isopropyl stilbene:

[0111] Take 8.22g (41.9mmol) of benzyl phosphate and 150mL of anhydrous tetrahydrofuran into the four-neck flask, stir, N 2 Protect, cool, add NaH at 0℃, then add dropwise A 1 After the addition of the tetrahydrofuran solution, the temperature was raised to reflux and monitored by TLC. After the reaction is completed, add water, extract with ethyl acetate, wash with water, and rotate to obtain product B 1 9.58g (34.0mmol). The yield was 86%.

[0112] c 1. Preparation of compound C1, 3,5-dihydroxy-4-isopropyl stilbene (phenenmod):

[0113] Earned from the previous step B 1 Add 23.5 g (203.8 mmol) of pyridine hydrochloride and pyridine hydrochloride to a 100 mL single-necked flask, heat to reflux, and monitor by TLC. After the reaction is completed, add water, extract with ethyl acetate, wash with water, and spin-evaporate to obtain product C 1 (Benzenemod) 6.64 g (26.2 mmol). The yield was 77%.

[0114] Some explanations in the method of synthesizing phenenemod by Pfitzner-moffatt oxidation reaction:

[0115] ①The molar ratio of 3,5-dimethoxy-4isopropylbenzyl alcohol to DMSO and acetic anhydride is 1:1-50:1-10;

[0116] ②The molar ratio of 3,5-dimethoxy-4isopropylbenzaldehyde to diethyl benzylphosphonate, THF and NaH is 1:1-10:20-100:0.5-10;

[0117] ③The tetrahydrofuran solution of 3,5-dimethoxy-4-isopropylbenzaldehyde added dropwise during the process is based on the ratio of 3,5-dimethoxy-4-isopropylbenzaldehyde to tetrahydrofuran as 1g: Prepared in a ratio of 2-50mL;

[0118] ④ The molar ratio of 3,5-dimethoxy-4 isopropyl stilbene to pyridine hydrochloride is 1:2-30.

Example Embodiment

[0119] Example 2 Method for synthesizing 3,5-dimethoxy-4'-hydroxystilbene, i.e. Pterocarpus stilbene, using Pfitzner-moffatt oxidation method

[0120] The reaction route of this embodiment is as shown in formula (III):

[0121]

[0122] Formula (III)

[0123] The reaction process is a 2 →b 2 →c 2 , The step-by-step reaction formula is as follows:

[0124]

[0125] This method is carried out in the following sequence of steps:

[0126] a 2.Compound A 2 Namely the preparation of 3,5-dimethoxybenzaldehyde:

[0127] 10.0 g (59.5 mmol) of 3,5-dimethoxybenzyl alcohol, 50 mL of DMSO, and 30 mL of acetic anhydride were added to a four-necked flask, stirred, and reacted at room temperature with TLC monitoring. After the reaction is completed, process, add water, extract with ethyl acetate, wash with water, and remove the solvent by rotary evaporation to obtain product A 2 8.55g (51.5mmol). The yield was 86.5%.

[0128] b 2. Preparation of compound B2, 3,5-dimethoxy-4'-tert-butyldimethylsiloxy stilbene:

[0129] Take 13.35g (25.8mmol) of 4'-tert-butyldimethylsiloxybenzyltriphenylphosphonium chloride and 80mL of tetrahydrofuran into a 500mL four-neck flask, add tert-butyllithium dropwise at -20℃ in an ice bath 15.5mL (16.4mmol), warm to room temperature after the addition is complete, stir for about 30min, add dropwise the obtained step A 2 THF solution, TLC monitoring. After the reaction is completed, add water, extract with ethyl acetate, wash with water, dry, and rotate to obtain product B 2 9.91g (26.8mmol). The yield was 52%.

[0130] c 2.Compound C 2 That is, the preparation of 3,5-dimethoxy-4'-hydroxystilbene (Pterocarpus stilbene):

[0131] Earned from the previous step B 2 Add 55mL of THF to a 250mL four-neck flask, stir, and add (n-Bu) dropwise 4 NF solution in THF (11.10mL/1M), react at room temperature for about 15min. The solvent was distilled off under reduced pressure and separated by column chromatography to obtain product C 2 (Pterocarpus stilbene) 3.63 g (14.2 mmol). The yield was 53%.

[0132] Some explanations in the method of synthesizing 3,5-dimethoxy-4'-hydroxystilbene, namely Pterocarpus stilbene, using the Pfitzner-moffatt oxidation method:

[0133] ①The molar ratio of 3,5-dimethoxy to DMSO and acetic anhydride is 1:1-50:1-10;

[0134] ②The molar ratio of 3,5-dimethoxybenzaldehyde to 4'-tert-butyldimethylsiloxybenzyltriphenylphosphonium chloride, THF and tert-butyllithium is 1:1-10:20-100 : 0.5-10;

[0135] ③The tetrahydrofuran solution of 3,5-dimethoxybenzaldehyde dropped in the process is prepared according to the ratio of 3,5-dimethoxybenzaldehyde to tetrahydrofuran of 1g:2-50mL;

[0136] ④In the last step of the preparation of Pterocarpus stilbene, the molar ratio of 3,5-dimethoxy-4'-tert-butyldimethylsiloxy stilbene, namely B2 to THF, is 1:20-100.

Example Embodiment

[0137] Example 3 Synthetic method of 3,4',5-trihydroxystilbene, resveratrol by Pfitzner-moffatt oxidation reaction

[0138] The reaction route of this embodiment is as shown in formula (IV):

[0139]

[0140] Formula (IV)

[0141] The reaction process is a 3 →b 3 →c 3 , The step-by-step reaction formula is as follows:

[0142]

[0143]

[0144] This method is carried out in the following sequence of steps:

[0145] a 3.Compound A 3 Namely the preparation of 3,5-dimethoxybenzaldehyde

[0146] 10.0 g (59.5 mmol) of 3,5-dimethoxybenzyl alcohol, 60 mL of DMSO, and 40 mL of acetic anhydride were added to a four-necked flask, stirred, and reacted at room temperature with TLC monitoring. After the reaction is completed, process, add water, extract with ethyl acetate, wash with water, and remove the solvent by rotary evaporation to obtain product A 3 8.87g (53.4mmol). The yield was 89.8%.

[0147] b 3. Preparation of compound B3, 3,4',5-trimethoxystilbene

[0148] Take 36.23g (160.3mmol) of 4′-methoxybenzyl phosphate and 120mL of anhydrous tetrahydrofuran into the four-necked flask, stir, N 2 Protect, cool, add NaH at 0℃, then add dropwise A 3 After the addition of the tetrahydrofuran solution, the temperature was raised to reflux and monitored by TLC. After the reaction is completed, add water, extract with ethyl acetate, wash with water, and rotate to obtain product B 3 11.97g (44.35mmol). The yield was 83.0%.

[0149] c 3.Compound C 3 That is, the preparation of 3,4',5-trimethoxystilbene (resveratrol):

[0150] Earned from the previous step B 3 Add 19.5 g (168.8 mmol) of pyridine hydrochloride and 19.5 g (168.8 mmol) to a 100 mL single-neck flask, and heat to reflux in an oil bath at 170° C., and TLC monitors. After the reaction is completed, add water, extract with ethyl acetate, wash with water, dry, filter with suction, and rotate to obtain product C 3 3.03g (13.3mmol), yield 30%.

[0151] Some explanations in the synthetic method one of the method of synthesizing 3,4',5-trihydroxystilbene, resveratrol by Pfitzner-moffatt oxidation reaction:

[0152] ①The molar ratio of 3,5-dimethoxybenzyl alcohol to DMSO and acetic anhydride is 1:1-50:1-10;

[0153] ②The molar ratio of 3,5-dimethoxybenzaldehyde to 4'-methoxybenzyl diethyl phosphate, THF, NaH is 1:1-10:20-100:0.5-10;

[0154] ③The tetrahydrofuran solution with 3,5-dimethoxybenzaldehyde added dropwise is prepared according to the ratio of 3,5-dimethoxybenzaldehyde to tetrahydrofuran of 1g: 2-50mL;

[0155] ④ The molar ratio of 3,4',5-trimethoxystilbene to pyridine hydrochloride is 1:2-30.

PUM

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