阅读说明：本技术 一种通过铑金属催化偶联的方式合成α,β–不饱和酮方法 (Method for synthesizing alpha, beta-unsaturated ketone by rhodium metal catalytic coupling ) 是由 岳燕妮 邓学祖 于 2021-05-27 设计创作，主要内容包括：本发明涉及了一种合成α,β–不饱和酮衍生物的方法,该方法通过金属催化剂铑催化烯基硅化合物与羧酸反应。步骤一：将烯基硅衍生物,羧酸,六水合氯化镁,四羰基二氯化二铑和二碳酸二叔丁酯加进放有磁子的干燥两口瓶中；步骤二：在氮气氛围下缓慢加入有机溶剂,通冷凝水,搅拌反应,待烯基硅衍生物完全反应,停止反应,冷却至室温；步骤三,进行过滤,洗涤,再将得到的滤液用旋转蒸发仪在低压下旋干,得到相应的α,β–不饱和酮。该发明相对于传统的合成α,β–不饱和酮的方法有以下优点：合成得到单一构型的；反应过程中不再需要加入碱性试剂,有毒试剂等；反应产率较高；方法的适用范围广,可得到一系列的α,β–不饱和酮类衍生物。(The invention relates to a method for synthesizing alpha, beta-unsaturated ketone derivatives, which uses rhodium as a metal catalyst to catalyze the reaction of alkenyl silicon compounds and carboxylic acid. The method comprises the following steps: adding alkenyl silicon derivative, carboxylic acid, magnesium chloride hexahydrate, rhodium dicarbonyl dichloride and di-tert-butyl dicarbonate into a dry two-mouth bottle with magnetons; step two: slowly adding an organic solvent in the nitrogen atmosphere, introducing condensed water, stirring for reaction, stopping the reaction when the alkenyl silicon derivative completely reacts, and cooling to room temperature; and step three, filtering and washing, and then carrying out spin-drying on the obtained filtrate by using a rotary evaporator under low pressure to obtain the corresponding alpha, beta-unsaturated ketone. Compared with the traditional method for synthesizing the alpha, beta-unsaturated ketone, the method has the following advantages that: synthesizing to obtain a single configuration; alkaline reagents, toxic reagents and the like are not required to be added in the reaction process; the reaction yield is high; the method has wide application range and can obtain a series of alpha, beta-unsaturated ketone derivatives.)

1. A method for synthesizing alpha, beta-unsaturated ketone by rhodium metal catalytic coupling is characterized in that: the method comprises the following steps:

the method comprises the following steps: adding alkenyl silicon derivative (formula I), carboxylic acid derivative (formula II), magnesium chloride hexahydrate, metal catalyst tetracarbonyl rhodium dichloride, magnesium chloride hexahydrate and di-tert-butyl dicarbonate into a drying bottle with magnetons, and filling a condenser pipe into two bottles;

slowly adding an organic solvent in the nitrogen atmosphere, introducing condensed water, stirring and reacting at 80-110 ℃, stopping the reaction until the alkenyl silicon derivative completely reacts, and cooling to room temperature;

step three, filtering and washing the mixture obtained in the step two, then carrying out spin-drying on the obtained filtrate by using a rotary evaporator under low pressure, and finally carrying out separation and purification on the obtained crude product by using a silica gel column to obtain a corresponding alpha, beta-unsaturated ketone derivative (formula three);

the specific reaction equation is as follows:

wherein R is¹Comprises the following steps: alkyl or phenyl; r²Comprises the following steps: alkyl or phenyl; r³Comprises the following steps: alkyl or phenyl; r⁴Is alkyl or phenyl, R⁵Is alkyl or phenyl.

2. The process of claim 1 for the synthesis of α, β -unsaturated ketones by way of rhodium metal catalyzed coupling, characterized in that: the carboxylic acid derivatives are selected from fatty acid, aromatic carboxylic acid or heterocyclic carboxylic acid.

3. The preparation method of the alpha, beta-unsaturated ketone derivative according to claim 2, wherein the preparation method comprises: the fatty acid is selected from formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, tertiary butyric acid, cyclohexanoic acid or cyclopentanoic acid.

4. The process of claim 1 for the synthesis of α, β -unsaturated ketones by way of rhodium metal catalyzed coupling, characterized in that: the aromatic carboxylic acid is selected from benzoic acid, phenylacetic acid, 2-naphthoic acid, p-methoxybenzoic acid or p-methoxyphenylacetic acid.

5. The process of claim 1 for the synthesis of α, β -unsaturated ketones by way of rhodium metal catalyzed coupling, characterized in that: the alkenyl silicon derivatives are selected from aliphatic, aromatic or heterocyclic alkenyl silicon.

6. The process of claim 1 for the synthesis of α, β -unsaturated ketones by way of rhodium metal catalyzed coupling, characterized in that: the temperature of the reaction is 100 ℃; the reaction time is 6-24 h.

7. The process of claim 1 for the synthesis of α, β -unsaturated ketones by way of rhodium metal catalyzed coupling, characterized in that: the reaction molar ratio is alkenyl silicon derivative: carboxylic acid derivatives: di-tert-butyl carbonate: dicarbonyl dirhodium dichloride: magnesium chloride hexahydrate of 1: 4: 3: 0.05: 0.1.

8. the process of claim 1 for the synthesis of α, β -unsaturated ketones by way of rhodium metal catalyzed coupling, characterized in that: the solvent is selected from benzene or toluene.

Technical Field

The invention belongs to the field of organic chemistry, and particularly relates to a method for synthesizing alpha, beta-unsaturated ketone.

Background

The alpha, beta-unsaturated ketone compound widely exists in nature, and has wide application prospect in various fields of biomedicine, organic chemical synthesis and the like. The methods for synthesizing the alpha, beta-unsaturated ketone are also various, such as dehydrosilicification reaction of silicon-based enol ether, Homer-Wadsworth-Emmons reaction/Witting reaction which uses a phosphorus reagent as a substrate, metal catalytic oxidation reaction, transition metal cross-coupling reaction and the like. However, these methods for synthesizing α, β -unsaturated ketones all have certain disadvantages, such as strong requirements for alkaline or acidic reaction conditions, low product yield, harsh reaction conditions, long reaction time, use of toxic reagents, low regioselectivity, and the like. The method uses transition metal rhodium as a catalyst, and alkenyl silicon and carboxylic acid as raw materials, so that the alpha, beta-unsaturated ketone compound with a single configuration is effectively synthesized, and the method has the advantages of high stability of the used reagent, no need of strong acid and strong alkali in the reaction process, wide reaction yield and reaction application range and the like.

Disclosure of Invention

The invention aims to provide an effective method for synthesizing alpha, beta-unsaturated ketone, which solves the defects of low yield, low chemical selectivity and the like of a traditional synthetic method because a strong acid and strong base reagent needs to be added in the reaction process through a metal rhodium catalytic coupling mode.

In order to solve the technical problem of the invention, the technical scheme is as follows: a method for synthesizing alpha, beta-unsaturated ketone by rhodium metal catalytic coupling, comprising the following steps:

the method comprises the following steps: adding alkenyl silicon derivative (formula I), carboxylic acid derivative (formula 2), magnesium chloride hexahydrate, metal catalyst tetracarbonyl rhodium dichloride, magnesium chloride hexahydrate and di-tert-butyl dicarbonate into a drying bottle with magnetons, and filling a condenser pipe into two bottles;

slowly adding an organic solvent in the nitrogen atmosphere, introducing condensed water, stirring and reacting at 80-110 ℃, stopping the reaction until the alkenyl silicon derivative completely reacts, and cooling to room temperature;

step three, filtering and washing the mixture obtained in the step two, then carrying out spin-drying on the obtained filtrate by using a rotary evaporator under low pressure, and finally carrying out separation and purification on the obtained crude product by using a silica gel column to obtain a corresponding alpha, beta-unsaturated ketone derivative (formula three);

the specific reaction equation is as follows:

wherein R is¹Comprises the following steps: alkyl or phenyl; r²Comprises the following steps: alkyl or phenyl; r³Comprises the following steps: alkyl or phenyl; r⁴Is alkyl or phenyl, R⁵Is alkyl orA phenyl group.

Preferably, the carboxylic acid derivative is selected from fatty acid, aromatic carboxylic acid or heterocyclic carboxylic acid.

Preferably, the fatty acid is selected from formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, tert-butyric acid, cyclohexanoic acid or cyclopentanecarboxylic acid.

Preferably, the aromatic carboxylic acid is selected from benzoic acid, phenylacetic acid, 2-naphthoic acid, p-methoxybenzoic acid or p-methoxyphenylacetic acid.

Preferably, the alkenyl silicon derivative is selected from aliphatic, aromatic or heterocyclic alkenyl silicon.

Preferably, the temperature of the reaction is 100 ℃; the reaction time is 6-24 h.

Preferably, the reaction molar ratio is alkenyl silicon derivative: carboxylic acid derivatives: di-tert-butyl carbonate: dicarbonyl dirhodium dichloride: magnesium chloride hexahydrate of 1: 4: 3: 0.05: 0.1.

preferably, the solvent is selected from benzene or toluene.

The specific experimental scheme of the invention is as follows:

the preparation scheme for synthesizing the alpha, beta-unsaturated ketone compound by rhodium catalysis is as follows:

the method comprises the following steps: alkenylsilicon derivative 1 of formula one (1equiv,0.1mmol), carboxylic acid 2 of formula two (4equiv,0.4mmol), magnesium chloride hexahydrate (20 mmol), dicarbonyldirhodium chloride ([ RhCl (CO))₂]₂) (5 mmol%) and di-tert-butyl dicarbonate ((t-BuOCO)₂)₂O) (3equiv,0.3mmol) was added to a dry 25ml two-necked flask with magnetite and a condenser tube was fitted to the two-necked flask;

step two: slowly adding 2ml of organic solvent benzene in the nitrogen atmosphere, introducing condensed water, stirring and reacting at 100 ℃, monitoring the reaction through a TLC plate, stopping the reaction when the alkenyl silicon derivative is completely reacted, and cooling to room temperature;

and step three, filtering and washing the mixture obtained in the step two, then carrying out spin-drying on the obtained filtrate by using a rotary evaporator under low pressure, and finally carrying out separation and purification on the obtained crude product by using a silica gel column to obtain the corresponding alpha, beta-unsaturated ketone compound shown as the formula three.

R in formula I, formula II and formula III₁Comprises the following steps: alkyl, phenyl, heterocyclic, substituted phenyl, benzoheterocyclic, and the like.

R in formula I, formula II and formula III₂Comprises the following steps: alkyl, phenyl, substituted phenyl, heterocyclic, and the like

In the formula I, R₃,R₄,R₅Is methyl or phenyl

In the second step, the reaction is monitored by a TLC plate, and the reaction time is 7-24h.

The alpha, beta-unsaturated ketone compound obtained in the third step is a single product with the (E) type configuration

The molar amount of dicarbonyl dirhodium dichloride mentioned in step one is 5 mmol%

The molar amount of dicarbonyl dirhodium dichloride mentioned in step one is 10 mmol%

The most preferred solvent used in step two is benzene, but is not limited to this solvent.

Compared with the prior art, the invention has the beneficial effects that:

1. the reaction system is simple, only a catalyst needs to be added in the reaction, the selected substrate is stable and easy to obtain, and the preparation cost is low;

2. the reaction system is clean, the conversion rate is high, the catalyst in the system is only required to be filtered, and the product is easy to separate;

3. the method has wide applicability, most common carboxylic acids are applicable to the method, the applicability of substrates is wide, and a series of alpha, beta-unsaturated ketone compounds can be prepared according to the method.

4. The metal catalysts used in the invention, namely the dicarbonyl dirhodium dichloride and the magnesium chloride hexahydrate, are unique catalysts which can catalyze the reaction and are obtained after screening conditions.

5. Additive (t-BuOCO) of the invention₂)₂The main function of O in the reaction is to promote carboxylic acid to generate anhydride, and the screening proves that O has uniqueness in the reaction.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.

FIG. 1 shows NMR of (E) -1, 5-diphenylpent-2-en-1-one provided in example 1 of the present invention¹H, spectrogram;

FIG. 2 shows NMR of (E) -1, 5-diphenylpent-2-en-1-one provided in example 1 of the present invention¹³C, spectrum;

FIG. 3 shows the NMR of (E) -chalcone provided in example 1 of the present invention¹H, spectrogram;

FIG. 4 shows the NMR of (E) -chalcone provided in example 1 of the present invention¹³C spectrum

FIG. 5 is the NMR of 6 phenylhex-3-en-2-one of example (E) of the present invention¹H, spectrogram;

FIG. 6 shows NMR spectra of 6-phenylhex-3-en-2-one of example (E) of the present invention¹³And C, spectrum.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

The method can synthesize various types of alpha, beta-unsaturated ketone compounds by the same mechanism according to different reaction substrate structures.

(1) The utility of the process was discussed using different classes of carboxylic acid compounds with (E) -dimethyl (phenyl) (4-phenylbut-1-ene) silane as the template substrate. The specific reaction equation is as follows:

wherein R is phenyl, p-methoxyphenyl, naphthyl, p-methoxybenzyl, cyclopropyl, cyclopentyl, methyl, butyl, tert-butyl, 2-tetrahydrofuryl, 2-furyl, 2-thienyl, etc. The structural formula is as follows:

(2) the utility of the method was discussed using different types of alkenyl silicon compounds with benzoic acid as the template substrate. The specific reaction equation is as follows:

wherein R is²Is methyl or phenyl, but is not limited to methyl or phenyl. The R group is 1-phenyl-propane, phenyl, cyclopentyl, cyclohexyl, tertiary butyl, cyclopentene, cyclohexene, furan, phenylpropane and the like. The concrete structure is as follows:

example 1

This example carries out the preparation of (E) -1, 5-diphenylpent-2-en-1-one. The specific operation is as follows:

under a nitrogen atmosphere, (E) -dimethyl (phenyl) (4-phenylbut-1-enyl) silane (0.1mmol), benzoic acid (0.4mmol), di-tert-butyl dicarbonate (0.3mmol), MgCl₂.6H₂O (10mmol％)，[RhCl(CO)₂]₂(5 mmol%) and benzene (2ml) were added to the flaskCondenser tube in 25ml two-necked flask. The reaction was monitored by TLC plate at 100 ℃ until (E) -dimethyl (phenyl) (4-phenylbut-1-ene) silane was completely reacted, heating was stopped and the reaction was cooled to room temperature. The resulting mixture was filtered through a sand funnel, washed with dichloromethane (10ml,3-5 times), and the solvent was evaporated with a rotary evaporator at low pressure to give a crude product. The crude product was purified by silica gel column chromatography (2% EA/PE) to give the desired product (E) -1, 5-diphenylpent-2-en-1-one as a colorless oily liquid in 73% yield (17.3 mg).

The result of the nuclear magnetic resonance hydrogen spectrum measurement of (E) -1,5 diphenyl pent-2-en-1-one is as follows:¹H NMR(400MHz,Chloroform-d)δ7.92–7.86(m,2H),7.59–7.53(m, 1H),7.49–7.43(m,2H),7.36–7.28(m,2H),7.25–7.19(m,3H),7.09 (dt,J＝15.4,6.8Hz,1H),6.88(dt,J＝15.4,1.4Hz,1H),2.86(t,J＝7.7 Hz,2H),2.74–2.56(m,2H).

the result of the nuclear magnetic resonance carbon spectrum measurement of (E) -1,5 diphenyl pent-2-en-1-one is as follows:¹³C NMR(101MHz,Chloroform-d)δ190.98,148.57,140.92,137.96, 132.78,128.66,128.62,128.52,126.65,126.31,34.64,34.59.

example 2

This example carries out the preparation of (E) -chalcone. The specific operation is as follows:

under a nitrogen atmosphere, (E) -dimethyl (phenyl) (styryl) silane (0.1mmol), benzoic acid (0.4mmol), di-tert-butyl dicarbonate (0.3mmol), MgCl₂.6H₂O(10 mmol％)，[RhCl(CO)₂]₂(5 mmol%) and benzene (2ml) were added to a 25ml two-necked flask equipped with a condenser tube. The reaction was monitored by TLC plate at 100 ℃ until (E) -dimethyl (phenyl) (styryl) silane was completely reacted, heating was stopped and the reaction was cooled to room temperature. The resulting mixture was filtered through a sand funnel, washed with dichloromethane (10ml,3-5 times), and the solvent was evaporated with a rotary evaporator at low pressure to give a crude product. Coarse product warp-knitted fabricPurification by gel column chromatography (2% EA/PE) gave the desired product (E) -chalcone as a colorless oily liquid in 60% yield (12.5 mg).

The result of the measurement of the (E) -chalcone nuclear magnetic resonance hydrogen spectrum is as follows:¹H NMR(400MHz, Chloroform-d)δ8.06–7.99(m,2H),7.82(d,J＝15.7Hz,1H),7.70– 7.48(m,6H),7.46–7.38(m,3H).

the result of the measurement of the (E) -chalcone nuclear magnetic resonance carbon spectrum is as follows:¹³C NMR(101MHz, Chloroform-d)δ190.74,145.01,138.33,135.01,132.94,130.71,129.11, 128.78,128.65,128.60,122.21.

example 3

This example proceeds to the preparation of (E) -6-phenylhex-3-en-2-one. The specific operation is as follows:

under nitrogen, (E) -dimethyl (phenyl) (4-phenylbut-1-ene) silane (0.1mmol), acetic acid (0.4mmol), di-tert-butyl dicarbonate (0.3mmol), MgCl₂.6H₂O (10mmol％)， [RhCl(CO)₂]₂(5 mmol%) and benzene (2ml) were added to a 25ml two-necked flask equipped with a condenser tube. The reaction was monitored by TLC plate at 100 ℃ until (E) -dimethyl (phenyl) (4-phenylbut-1-ene) silane was completely reacted, heating was stopped and the reaction was cooled to room temperature. The resulting mixture was filtered through a sand funnel, washed with dichloromethane (10ml,3-5 times), and the solvent was evaporated with a rotary evaporator at low pressure to give a crude product. The crude product was purified by silica gel column chromatography (2% EA/PE) to give the desired product (E) -6-phenylhex-3-en-2-one as a colorless oily liquid in 79% yield (13.8 mg).

The result of the nuclear magnetic resonance hydrogen spectrum measurement of the (E) -6 phenylhex-3-en-2-one is as follows: 1H NMR (400MHz, Chloroform-d) δ 7.34-7.27 (m,2H), 7.25-7.16 (m, 3H),6.82(dt, J ═ 15.9,6.8Hz,1H),6.10(d, J ═ 16.0Hz,1H), 2.87-2.71 (m,2H), 2.65-2.46 (m,2H),2.23(s,3H).

The result of the nuclear magnetic resonance carbon spectrum measurement of the (E) -6 phenylhex-3-en-2-one is as follows: 13C NMR (101MHz, Chloroform-d) delta 198.84,147.33,131.78,128.62,128.42, 126.34,34.48,34.25,27.01.

Comparative example 1

This comparison is compared with the preparation of 1(E) -1, 5-diphenylpent-2-en-1-one of the examples, the specific operating procedure being as follows:

under a nitrogen atmosphere, (E) -dimethyl (phenyl) (4-phenylbut-1-enyl) silane (0.1mmol), benzoic acid (0.4mmol), di-tert-butyl dicarbonate (0.3mmol), MgCl₂.6H₂O (10mmol％)，[RhOH(COD)₂]₂(5 mmol%) and benzene (2ml) were added to a 25ml two-necked flask equipped with a condenser tube. Reaction at 100 ℃ and after 12h, no product formation and no conversion of (E) -dimethyl (phenyl) (4-phenylbut-1-enyl) silane occurred.

Comparative example 2

This comparison is compared with the preparation of 1(E) -1, 5-diphenylpent-2-en-1-one of the examples, the specific operating procedure being as follows:

under nitrogen, (E) -dimethyl (phenyl) (4-phenylbut-1-enyl) silane (0.1mmol), benzoic acid (0.4mmol), MgCl₂.6H₂O(10mmol％)，[RhCl(CO)₂]₂(5 mmol%) and benzene (2ml) were added to a 25ml two-necked flask equipped with a condenser tube. Reaction at 100 ℃ and after 12h, no product formation and no conversion of (E) -dimethyl (phenyl) (4-phenylbut-1-enyl) silane occurred.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.