阅读说明：本技术 由有机硒代硫酸钠合成α-硒基-α,β-不饱和羰基化合物的方法 (Method for synthesizing alpha-seleno-alpha, beta-unsaturated carbonyl compound by using organic seleno sodium sulfate ) 是由 仇晃耀 张志国 易文斌 刘帆敏 赫五卷 于 2021-01-15 设计创作，主要内容包括：本发明公开了一种由有机硒代硫酸钠合成α-硒基-α,β-不饱和羰基化合物的方法。所述方法以α,β-不饱和羰基化合物和有机硒代硫酸钠为原料,在碘的催化下,以二甲亚砜为溶剂,在60～80℃下充分反应制得α-硒基-α,β-不饱和羰基化合物。本发明方法工艺条件合理,操作简单安全；避免使用气味难闻的硒醇等原料,无需金属催化剂,环境友好。(The invention discloses a method for synthesizing alpha-seleno-alpha, beta-unsaturated carbonyl compounds by using organic selenosulfate. The method takes alpha, beta-unsaturated carbonyl compound and organic sodium selenosulfate as raw materials, takes dimethyl sulfoxide as solvent under the catalysis of iodine, and fully reacts at 60-80 ℃ to prepare the alpha-seleno-alpha, beta-unsaturated carbonyl compound. The method has reasonable process conditions and simple and safe operation; avoids using raw materials such as selenol with unpleasant smell and the like, does not need a metal catalyst, and is environment-friendly.)

1. The method for synthesizing the alpha-seleno-alpha, beta-unsaturated carbonyl compound by using the organic selenosulfate is characterized in that the reaction formula is as follows:

the method comprises the following specific steps: alpha, beta-unsaturated carbonyl compound shown in formula (II) and organic seleno sodium sulfate shown in formula (III) are used as raw materials, and iodine (I)₂) Taking dimethyl sulfoxide (DMSO) as a solvent as a catalyst, fully reacting at 60-80 ℃, and after the reaction is finished, separating and purifying reaction liquid to obtain an alpha-seleno-alpha, beta-unsaturated carbonyl compound shown in a formula (I); the alpha, beta-unsaturated carbonyl compound is selected from benzalacetone or chromone, and R in the formula (I) and the formula (III)₂Selected from benzyl or phenyl.

2. The method according to claim 1, wherein the molar ratio of the α, β -unsaturated carbonyl compound to the sodium organoselenosulfate is 1:1 to 1: 1.5.

3. The method according to claim 1, wherein the molar ratio of the α, β -unsaturated carbonyl compound to the sodium organoselenosulfate is 1:1.4 to 1: 1.5.

4. The method according to claim 1, wherein the molar amount of iodine is 0.1 to 0.4 times the molar amount of the α, β -unsaturated carbonyl compound.

5. The method according to claim 1, wherein the molar amount of iodine is 0.2 to 0.3 times the molar amount of the α, β -unsaturated carbonyl compound.

6. The method according to claim 1, wherein the molar amount of dimethyl sulfoxide is 50 to 80 times that of the α, β -unsaturated carbonyl compound.

7. The method according to claim 1, wherein the molar amount of dimethyl sulfoxide is 60 to 70 times the molar amount of the α, β -unsaturated carbonyl compound.

8. The method according to claim 1, wherein the reaction temperature is 65 to 75 ℃.

9. The process according to claim 1, wherein the reaction time is 6 to 10 hours, preferably 7 to 8 hours.

10. The method according to claim 1, wherein the separation and purification method comprises: after the reaction is finished, adding water into the reaction liquid for dilution, extracting for 3 times by ethyl acetate, combining organic phases, washing by saturated saline solution, separating and taking an organic layer, drying by anhydrous sodium sulfate, carrying out reduced pressure distillation to remove the solvent, separating the crude product by column chromatography to obtain the alpha-seleno-alpha, beta-unsaturated carbonyl compound, wherein the eluent is a compound with a volume ratio of 10-20: 1 of petroleum ether and ethyl acetate.

Technical Field

The invention relates to the field of organic synthesis, and relates to a method for synthesizing an alpha-seleno-alpha, beta-unsaturated carbonyl compound from organic seleno-sodium sulfate.

Background

Alpha-seleno-alpha, beta-unsaturated carbonyl compound is an important synthetic intermediate in the field of organic synthesis, corresponding 1, 3-diene is formed through Wittig reaction, then allyl [2,3] -sigma rearrangement of seleno is carried out, corresponding alpha-propadiene, alpha-allenamine or alpha-propadiene chloride can be generated, or the compound directly serves as conjugated diene to generate heteroatom Diels-Alder reaction with olefin, and corresponding dihydropyran is generated. In addition, the alpha-seleno-alpha, beta-unsaturated carbonyl compound can also be used as a Z-allyl precursor to participate in subsequent reactions so as to maintain the configuration. Therefore, the synthesis of α -seleno- α, β -unsaturated carbonyl compounds is an important issue in organic synthesis. Many synthetic methods have been reported so far, for example:

document 1(Berlin S, Engman L.A radial circulation route to pyrolidines based on connected addition to electronic benzene substituents [ J]Tetrahedron Letters,2000,41(19):3701-3704) Berlin et al use an α, β -unsaturated carbonyl compound and phenylselenium chloride with the aid of zinc chloride with dichloromethane (CH)₂Cl₂) Is used as a solvent to obtain an addition product, and then one molecule of hydrogen chloride is removed under the alkaline condition to synthesize the alpha-seleno-alpha, beta-unsaturated carbonyl compound. The method needs two steps of reaction, toxic phenyl selenium chloride is used, and the substrate applicability of the reaction is poor due to the lack of organic selenium chloride, and the reaction formula is as follows:

document 2(Redon S, Berth Berkaoui A-L, Pannecake X, Outurquin F. selenized dienes: Synthesis, stereochemical studios by 77se nmr, and transformation into functionalized olefins [ J ]. Tetrahedron,2007,63(18): 3707-. The method avoids using selenium chloride which has bad smell and is toxic, but the reaction only realizes the substitution reaction of selenophenyl, and the reaction formula is as follows:

document 3 (Silverra C, Guerra R B, Comasseto J V. stereoselective synthesis of viral peptides through viral Substruction by lithium organic carbonyl peptides [ J ]. Tetrahedron Letters,2007,48(29):5121-5124) Silvera et al use a 1, 3-dicarbonyl compound as a starting material, react with lithium selenide under a strong alkali sodium hydride to obtain an α -seleno-dicarbonyl compound, and then react with diethyl chlorophosphate under another equivalent of sodium hydride to synthesize the corresponding α -seleno- α, β -unsaturated carbonyl compound. The method requires multiple reactions and the presence of large amounts of strong base, and the seleno-lithium is prepared according to the following reaction formula:

the above methods have some disadvantages, such as limited raw materials, small substrate range, or inevitable use of selenium halide compounds with unpleasant odor, and some reactions require the use of metal catalysts and additives, which also increase the reaction cost, cause great harm to the environment, and are not in line with the development of green chemistry. Therefore, a more suitable reaction is sought, and the use of reagents having a large influence on the environment is avoided.

Disclosure of Invention

The invention aims to provide a method for synthesizing alpha-seleno-alpha, beta-unsaturated carbonyl compounds by using organic selenosulfate, which has reasonable process, low toxicity and high reaction efficiency.

The technical scheme for realizing the purpose of the invention is as follows:

the method for synthesizing the alpha-seleno-alpha, beta-unsaturated carbonyl compound by using the organic seleno sodium sulfate has the following reaction formula:

the method comprises the following specific steps: alpha, beta-unsaturated carbonyl compound shown in formula (II) and organic seleno sodium sulfate shown in formula (III) are used as raw materials, and iodine (I)₂) Taking dimethyl sulfoxide (DMSO) as a solvent as a catalyst, fully reacting at 60-80 ℃, and after the reaction is finished, separating and purifying reaction liquid to obtain an alpha-seleno-alpha, beta-unsaturated carbonyl compound shown in a formula (I); the alpha, beta-unsaturated carbonyl compound is selected from benzalacetone or chromone, and R in the formula (I) and the formula (III)₂Selected from benzyl or phenyl.

Further, the molar ratio of the alpha, beta-unsaturated carbonyl compound to the organic sodium selenosulfate is 1:1 to 1:1.5, preferably 1:1.4 to 1: 1.5.

Further, the molar amount of iodine is 0.1 to 0.4 times, preferably 0.2 to 0.3 times the molar amount of the α, β -unsaturated carbonyl compound.

Further, the molar amount of dimethyl sulfoxide is 50 to 80 times, preferably 60 to 70 times the molar amount of the α, β -unsaturated carbonyl compound.

Further, the reaction temperature is preferably 65-75 ℃.

Further, the reaction time is 6-10 h, preferably 7-8 h.

Further, the separation and purification method comprises the following steps: after the reaction is finished, adding water into the reaction liquid for dilution, extracting for 3 times by ethyl acetate, combining organic phases, washing by saturated saline solution, separating and taking an organic layer, drying by anhydrous sodium sulfate, carrying out reduced pressure distillation to remove the solvent, separating the crude product by column chromatography to obtain the alpha-seleno-alpha, beta-unsaturated carbonyl compound, wherein the eluent is a compound with a volume ratio of 10-20: 1 of petroleum ether and ethyl acetate.

Compared with the prior art, the invention has the following advantages:

(1) reasonable process conditions and simple and safe operation.

(2) Avoids using raw materials with unpleasant smell, has rich types of starting raw materials, few three wastes and is environment-friendly.

(3) The application range of the substrate is wide, and the yield of the reaction is improved.

Detailed Description

The present invention will be described in more detail with reference to specific examples.

Reference to the preparation of sodium organoselenosulfate used in the following examples: crich D, Krishnhancythy V, Hutton T K. Allylic Selenosulfide reading A Method for Chemical Ligation to Cysteine and Other metals [ J ] Journal of the American Chemical Society,2006,128(25):2544-5 ].

Example 1

To a 35mL thick-walled pressure tube were added 0.073g (0.5mmol) of benzylidene acetone, 0.2055g (0.75mmol) of sodium benzylselenosulfate, 0.0254g (0.1mmol) of iodine and 2mL (25mmol) of dimethyl sulfoxide. The reaction was stirred at 70 ℃ for 8 h. After the reaction, the reaction mixture was diluted with 20mL of water, extracted 3 times with 15mL of ethyl acetate, the organic phases were combined, washed with saturated brine, the organic phase was separated, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The crude product was isolated by column chromatography (eluent was a mixture of petroleum ether and ethyl acetate in a volume ratio of 10: 1) to yield 0.1153g of α -benzylseleno-benzylidene acetone in 73% yield.

Process for preparing alpha-benzylseleno-benzylidene acetone¹H NMR and¹³the C NMR data are as follows.

¹H NMR(500MHz,Chloroform-d)δ7.53(d,J＝15.9Hz,1H),7.48–7.45(m,2H),7.34–7.28(m,4H),7.22(t,J＝7.4Hz,2H),7.15(q,J＝7.4,6.0Hz,1H),6.78(d,J＝16.0Hz,1H),3.73(s,2H),3.28(s,3H)；

¹³C NMR(126MHz,Chloroform-d)δ194.25,143.55,138.46,134.56,130.74,129.44,129.10,128.76,128.63,127.21,124.31,30.51,28.27。

Example 2

To a 35mL thick-walled pressure tube were added 0.073g (0.5mmol) chromone, 0.195g (0.75mmol) sodium phenylselenosulfate, 0.0254g (0.1mmol) iodine, and 2mL (25mmol) of dimethyl sulfoxide. The reaction was stirred at 70 ℃ for 8 h. After the reaction, the reaction mixture was diluted with 20mL of water, extracted 3 times with 15mL of ethyl acetate, the organic phases were combined, washed with saturated brine, the organic phase was separated, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The crude product was isolated by column chromatography (eluent was a mixture of petroleum ether and ethyl acetate at a volume ratio of 20: 1) to yield 0.1042g of α -phenylseleno-chromone in 69% yield.

Process for preparing alpha-phenylseleno-chromones¹H NMR and¹³c NMR data are as follows。

¹H NMR(500MHz,Chloroform-d)δ8.23(d,J＝8.0Hz,1H),7.88(d,J＝0.9Hz,1H),7.70-7.56(m,3H),7.41(dd,J＝9.7,8.2Hz,2H),7.34-7.24(m,3H)；

¹³C NMR(126MHz,Chloroform-d)δ175.27,156.47,155.86,133.98,133.93,129.64,128.31,128.23,126.47,125.89,123.30,118.18,118.02。

Example 3

This example is essentially the same as example 1, except that the reaction temperature is 60 ℃. The yield was 68%.

Example 4

This example is essentially the same as example 1, except that the reaction temperature is 80 ℃. The yield was 71%.

Comparative example 1

This comparative example is essentially the same as example 1, except that potassium iodide was added as the catalyst. The yield was 56%.

Comparative example 2

This comparative example is essentially the same as example 1, except tetrabutylammonium iodide was added as catalyst. The yield was 62%.

Comparative example 3

This comparative example is essentially the same as example 1, except that water is used as the solvent. The yield was 0%.

Comparative example 4

This comparative example is essentially the same as example 1, except that dimethyl sulfoxide/water (1: 1 by volume) was used as the solvent. The yield was 43%.

Comparative example 5

This comparative example is essentially the same as example 1, except that the reaction temperature is 100 ℃. The yield was 53%.

Comparative example 6

This comparative example is essentially the same as example 1, except that the reaction temperature is 40 ℃. The yield was 41%.

Comparative example 7

This comparative example is essentially the same as example 1, except that coumarin is used as the reaction substrate. The yield was 0%.

Although coumarin also belongs to the group of α, β -unsaturated carbonyl compounds, it is not suitable for the synthesis of the corresponding α -seleno- α, β -unsaturated carbonyl compounds by the process of the present invention.

The above embodiments do not limit the present invention in any way, and all technical solutions obtained by means of equivalent substitution or equivalent transformation fall within the protection scope of the present invention.