CN109942364A - A kind of olefin synthesis method using water as hydrogen source - Google Patents

Abstract

The invention discloses an olefin synthesis method using water as a hydrogen source. In this method, alkyne is used as synthesis raw material, cobalt compound is used as catalyst, water is used as hydrogen source, and olefin is synthesized by transfer hydrogenation reaction. In the present invention, adding a bisphosphine ligand to the reaction system can obtain a trans olefin, and if no ligand is added, a cis olefin can be obtained. The present invention provides a mild, efficient, universal and highly efficient synthesis method of cis/trans olefins with adjustable chemical selectivity.

Description

A kind of olefin synthesis method using water as hydrogen source

technical field

The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing olefins using water as a hydrogen source.

Background technique

Highly selective semi-reductive hydrogenation of alkynes is an important method to obtain single-configuration alkenes. In recent decades, it has mainly relied on noble metal catalytic hydrogenation (such as the classic Lindela palladium catalyst). Therefore, the development and development of inexpensive metal Catalysts and greener, more economical sources of hydrogen are of great significance. In the semi-reductive hydrogenation of alkynes, in order to obtain more alkene products with a single configuration, high reaction selectivity is required. Therefore, the construction of a tunable and highly selective semi-reductive hydrogenation catalytic system has become a worthy challenge for the majority of scientific researchers. Water is one of the most common substances in nature. It is the most ideal hydrogen source because of its cheap and environmentally friendly properties. The transfer hydrogenation reaction using water as a hydrogen source is economical, environmentally friendly, mild and efficient.

In the molecular structure of natural products and pharmaceuticals, the cis-trans isomerism of alkenes widely exists. For example, the stilbene-based natural products widely distributed in various plants are mainly in the trans configuration, mostly in the form of aglycones or glycosides. , and often form a trans-3,4',5-trihydroxystilbene (resveratrol) skeleton and its derivatives. Trans-stilbene compounds often have many important biological activities such as anti-senile dementia, anti-cancer, antibacterial, anti-oxidation, and lowering blood lipids, which have attracted great attention and in-depth research by scholars at home and abroad. In medicinal chemistry, cis-alkenes represent an important class of pharmacodynamic structures and are widely present in many biologically active molecules, such as 11-cis-retinal (11-cis-retinal), which plays a key role in the formation of human vision. -retinal); the antipsychotic drug chlorprothixene (chlorprothixene), its molecular structure contains double bonds, so there are cis and trans isomers, of which the antipsychotic effect of cis is eight times that of trans; from South African dwarf willow bark CombretastatinA-4 isolated from , showed strong antitumor activity as a potent tubulin inhibitor, and the compound had therapeutic effect only when it was in the cis configuration.

It can be seen that the method of synthesizing olefins with specified configuration with high selectivity has broad application prospects. It is of great significance to use cheap metal catalysis to construct an economical, environmentally friendly and highly selective catalytic system.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a method for synthesizing olefins using water as a hydrogen source.

The object of the present invention is achieved by the method for synthesizing olefins using water as a hydrogen source, which is to synthesize olefins through a transfer hydrogenation reaction by using an inner alkyne as a synthesis raw material, a cobalt compound as a catalyst, and water as a hydrogen source.

The invention is a high-selective synthesis method of cis/trans olefins with cheap metal catalysis, water as hydrogen source, simple operation, mild reaction, high efficiency and good universality.

The present invention adopts the following technical solutions to realize:

1. The cobalt catalysts used are cobalt iodide, cobalt bromide, cobalt chloride, cobalt acetate, cobalt acetylacetonate, etc.

2. The ligands used are bisphosphine ligands: dppe, dppm, dppp, dppb, dppf, dppen, XantPhos, rac-Binap, dinitrogen ligands: 1,10-phen, monophosphine ligands: PPh ₃ , which The molecular structures are:

.

3. The molecular structure of internal alkyne is:

.

4. The high-selectivity synthesis method of cis/trans olefins with inner alkyne as starting material cobalt catalysis with water as hydrogen source comprises the following steps:

Synthesis steps for cis-alkenes:

(1) Using inner acetylene as raw material, in the glove box, accurately weigh cobalt iodide (0.01 mmol), reducing agent zinc powder (0.6 mmol), and any inner acetylene (0.2 mmol), and add them in turn to a stirring bar. The Snake reaction tube is plugged with a rubber stopper and removed from the glove box.

(2) Aspirate 2 mL of methanol and 36 μL of water, and add them to the reaction tube in turn. The reaction was stirred under a constant temperature magnetic stirrer at 60°C, and the reaction progress was monitored by TLC.

(3) After the reaction is completed, the reaction tube is taken out, the volatile solvent is removed from the reaction solution under reduced pressure, and the cis olefin is obtained by purification by column chromatography.

Synthesis steps for trans-alkenes:

(1) Using inner alkyne as raw material, in a glove box, accurately weighed cobalt iodide (0.01 mmol) and dppe ligand (0.012 mmol) were added to a Snake reaction tube with a stirrer, and 1 mL of acetonitrile was added to dissolve it. , and stirred at room temperature for 30 min with a magnetic stirrer.

(2) Accurately weigh the reducing agent zinc (0.6 mmol) and any arylidene (0.2 mmol), add them to the reaction tube in turn, add 1 mL of acetonitrile, plug the rubber stopper and remove the glove box.

(3) Pipette 36 μL (2 mmol) of water into the reaction tube. The reaction was stirred under a constant temperature magnetic stirrer at 60°C, and the reaction progress was monitored by TLC.

(4) After the reaction is completed, the reaction tube is taken out, the volatile solvent is removed from the reaction solution under reduced pressure, and the trans-olefin is obtained by purification by column chromatography.

The above process can be represented by the following chemical equation:

.

In the above steps, the metal catalyst is any one of cobalt iodide, cobalt bromide, cobalt chloride, cobalt acetate, and cobalt acetylacetonate, and the preferred metal catalyst is cobalt iodide.

In the above-mentioned cis-olefin synthesis step, the solvent used is any one or more of methanol, ethanol, isopropanol, trifluoroethanol, acetonitrile, tetrahydrofuran, dioxane and toluene, wherein the preferred solvent is methanol.

In the synthesis step of above-mentioned trans olefin, the solvent used is any one or more of acetonitrile, tetrahydrofuran, dioxane, toluene, N,N-dimethylformamide, sulfoxide, and methanol, wherein preferably The solvent is acetonitrile.

In the synthesis steps of above-mentioned trans olefins, the ligand used is a bisphosphine ligand: dppe, dppm, dppp, dppb, dppf, dppen, XantPhos, rac-Binap, two nitrogen ligands: 1,10-phen, monophosphine ligand Body: any of PPh ₃ , wherein the preferred ligand is dppe.

In the above steps, the reducing agent used includes one or more of zinc powder, manganese powder, magnesium powder and iron powder of simple metal, wherein the preferred reducing agent is zinc powder.

Compared with the prior art, the technical scheme that can be used in the present invention has the following advantages:

1. The present invention utilizes the strategy of adopting cheap transition metal cobalt catalysis, and uses water as a hydrogen source to prepare cis or trans olefin compounds with high selectivity, which can greatly reduce production costs and have significant social and economic benefits.

2. The catalytic system of the present invention is simple, easy to operate, and good in selectivity.

3. Under the catalysis of cobalt iodide, the present invention can realize the highly selective regulation of the configuration of the reaction product by adjusting the conditions of the ligand and solvent.

Detailed ways

The present invention is further described below in conjunction with the examples, but the present invention is not limited in any way, and any transformation or replacement made based on the teachings of the present invention belongs to the protection scope of the present invention.

The method for synthesizing olefins using water as a hydrogen source according to the present invention is to synthesize olefins through a transfer hydrogenation reaction by using an alkyne as a synthesis raw material, a cobalt compound as a catalyst, and water as a hydrogen source.

The olefin synthesis method using water as a hydrogen source includes a cis olefin synthesis method and a trans olefin synthesis method.

Described cis olefin synthesis method comprises the following steps:

A. First, the molar ratio of cobalt compound, reducing agent and internal alkyne is 1:(50~70):(10~30) and successively added to the reaction vessel to obtain material a;

B. In material a, add methanol whose molar volume ratio (ml: mmol) of cobalt compound is (100~300): 1 and water whose molar volume ratio (μl: mmol) is (3000~4000): 1 in turn The reaction was stirred at a constant temperature at a temperature of 50-70 °C, and the reaction progress was monitored by TLC. After the reaction, the volatile solvent was removed from the reaction solution under reduced pressure, and the target cis olefin was obtained by column chromatography purification.

Described trans olefin synthesis method comprises the following steps:

A. First, the cobalt compound and the ligand are added to the reaction vessel in a molar ratio of 1:(1~1.5), and then the acetonitrile with a molar volume ratio (ml:mmol) of the cobalt compound (50~150):1 is added and stirred 20~40min to get material a after dissolving;

B. In the material a, add the reducing agent and internal alkyne with the molar ratio of cobalt compound as 1:(50~70):(10~30) in turn, and then add the molar volume ratio of cobalt compound (ml:mmol) to be (50 ~150): 1 of acetonitrile to obtain material b;

C. Add water with a molar volume ratio (μl: mmol) of (3000~4000): 1 to material b, then stir the reaction at a constant temperature at a temperature of 50~70°C, and use TLC to monitor the reaction process. After the reaction, the reaction solution The volatile solvent was removed under reduced pressure and purified by column chromatography to obtain the target trans-olefin.

The cobalt compound is one or more of cobalt iodide, cobalt bromide, cobalt chloride, cobalt acetylacetonate, and cobalt acetate.

The reducing agent is one or more of metal elemental zinc powder, manganese powder, magnesium powder or iron powder.

The internal alkyne is a diaryl internal alkyne, a monoaryl aliphatic internal alkyne, a monoaryl internal alkyne ester or an aliphatic internal alkyne.

The ligand is dppe, dppm, dppp, dppb, dppf, dppen, XantPhos, rac-Binap, 1,10-phen or PPh ₃ .

The present invention is further described below with specific implementation cases:

Example 1

In the glove box, sequentially weigh cobalt iodide (0.01 mmol), zinc powder (0.6 mmol), and the above-mentioned alkyne (0.2 mmol) accurately and put them into a Snake reaction tube with a stirrer, and plug it with a rubber stopper. Remove the glove box, take 2 ml of methanol from the syringe, add 36 μL (2 mmol) of water to the reaction tube from the micro-injector, and place it in a constant temperature magnetic stirrer at 60 °C to stir the reaction, and use TLC to monitor the reaction process. After the reaction was completed, the reactor was opened and volatiles were removed using a rotary evaporator under reduced pressure, and purified by column chromatography using ethyl acetate and petroleum ether as eluents. The reaction solvent was concentrated under reduced pressure, and then purified by column chromatography to obtain a stilbene compound (99% yield, Z/E = 90:10). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.30 - 7.12 (m, 10H), 6.59 (s, 2H).

Example 2

In the glove box, sequentially weigh cobalt iodide (0.01 mmol), zinc powder (0.6 mmol), and the above-mentioned alkyne (0.2 mmol) accurately and put them into a Snake reaction tube with a stirrer, and plug it with a rubber stopper. Remove the glove box, take 2 ml of methanol from the syringe, add 36 μL (2 mmol) of water to the reaction tube from the micro-injector, and place it in a constant temperature magnetic stirrer at 60 °C to stir the reaction, and use TLC to monitor the reaction process. After the reaction was completed, the reactor was opened and volatiles were removed using a rotary evaporator under reduced pressure, and purified by column chromatography using ethyl acetate and petroleum ether as eluents. The reaction solvent was concentrated under reduced pressure, and then purified by column chromatography to obtain a stilbene compound (96% yield, Z/E: 90:10). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.28 – 7.14 (m, 7H), 6.74 (d, J = 8.8 Hz, 2H), 6.51 (s, 2H), 3.76 (s, 3H).

Example 3

In the glove box, sequentially weigh cobalt iodide (0.01 mmol), zinc powder (0.6 mmol), and the above-mentioned alkyne (0.2 mmol) accurately and put them into a Snake reaction tube with a stirrer, and plug it with a rubber stopper. Remove the glove box, take 2 ml of methanol from the syringe, add 36 μL (2 mmol) of water to the reaction tube from the micro-injector, and place it in a constant temperature magnetic stirrer at 60 °C to stir the reaction, and use TLC to monitor the reaction process. After the reaction was completed, the reactor was opened and volatiles were removed using a rotary evaporator under reduced pressure, and purified by column chromatography using ethyl acetate and petroleum ether as eluents. The reaction solvent was concentrated under reduced pressure, and then purified by column chromatography to obtain a stilbene compound (98% yield, Z/E = 91:9). ¹ H NMR (400 MHz, CDCl ₃ ) δ7.33 (d, J = 8.4 Hz, 2H), 7.26 – 7.18 (m, 5H), 7.10 (d, J = 8.3 Hz, 2H), 6.56 (dd, J = 52.0, 12.2 Hz, 2H).

Example 4

In a glove box, accurately weigh cobalt iodide (0.01 mmol) and dppe (0.012 mmol) and put them into a Snake reaction tube with a stirring bar, add 1 mL of acetonitrile to dissolve, and place it on a magnetic stirrer at room temperature Stir for 30min to make the complexation fully. Then accurately weighed zinc powder (0.6 mmol) and the above-mentioned internal alkyne (0.2 mmol) were added to the reaction tube in turn, and 1 mL of acetonitrile was added, plugged with a rubber stopper and removed from the glove box. The micro-injector sucked 36 μL (2 mmol) of water into the reaction tube, placed it in a constant temperature magnetic stirrer at 60 °C to stir the reaction, and monitored the reaction progress by TLC. After the reaction was completed, the reactor was opened and volatiles were removed using a rotary evaporator under reduced pressure, and purified by column chromatography using ethyl acetate and petroleum ether as eluents. The reaction solvent was concentrated under reduced pressure, and then purified by column chromatography to obtain a stilbene compound (99% yield, Z/E = 97:3). ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.50 (d, J = 7.7 Hz, 4H), 7.34 (t, J = 7.6 Hz, 4H), 7.25 (dd, J = 8.4, 6.2 Hz, 2H), 7.10 ( d, J = 2.4 Hz, 2H).

Example 5

In a glove box, accurately weigh cobalt iodide (0.01 mmol) and dppe (0.012 mmol) and put them into a Snake reaction tube with a stirring bar, add 1 mL of acetonitrile to dissolve, and place it on a magnetic stirrer at room temperature Stir for 30min to make the complexation fully. Then accurately weigh zinc powder (0.6 mmol) and the above-mentioned internal alkyne (0.2 mmol) into the reaction tube in turn, and add 1 mL of acetonitrile, plug it with a rubber stopper and remove it from the glove box. The micro-injector sucked 36 μL (2 mmol) of water into the reaction tube, placed it in a constant temperature magnetic stirrer at 60 °C to stir the reaction, and monitored the reaction progress by TLC. After the reaction was completed, the reactor was opened and volatiles were removed using a rotary evaporator under reduced pressure, and purified by column chromatography using ethyl acetate and petroleum ether as eluents. The reaction solvent was concentrated under reduced pressure, and then purified by column chromatography to obtain a stilbene compound (98% yield, Z/E = 7:93). ¹ HNMR (400 MHz, CDCl3) δ 7.46 (dd, J = 14.5, 8.0 Hz, 4H), 7.33 (t, J = 7.6 Hz, 2H), 7.25 – 7.19 (m, 1H), 7.01 (dd, J = 38.4, 16.3 Hz, 2H), 6.89 (d, J = 8.8Hz, 2H), 3.80 (s, 3H).

Example 6

In a glove box, accurately weigh cobalt iodide (0.01 mmol) and dppe (0.012 mmol) and put them into a Snake reaction tube with a stirring bar, add 1 mL of acetonitrile to dissolve, and place it on a magnetic stirrer at room temperature Stir for 30min to make the complexation fully. Then accurately weigh zinc powder (0.6 mmol) and the above-mentioned internal alkyne (0.2 mmol) into the reaction tube in turn, and add 1 mL of acetonitrile, plug it with a rubber stopper and remove it from the glove box. The micro-injector sucked 36 μL (2 mmol) of water into the reaction tube, placed it in a constant temperature magnetic stirrer at 60 °C to stir the reaction, and monitored the reaction progress by TLC. After the reaction was completed, the reactor was opened and volatiles were removed using a rotary evaporator under reduced pressure, and purified by column chromatography using ethyl acetate and petroleum ether as eluents. The reaction solvent was concentrated under reduced pressure, and then purified by column chromatography to obtain a stilbene compound (70% yield, Z/E = 5:95). ¹ HNMR (400 MHz, CDCl ₃ ) δ 7.56 – 7.45 (m, 4H), 7.38 (dd, J = 8.1, 6.2 Hz, 4H), 7.32 – 7.26 (m, 1H), 7.07 (q, J = 16.3 Hz , 2H).

The above-mentioned embodiments are only for illustrating the technical concept and characteristics of the present invention, and all equivalent changes or modifications made according to the spirit of the present invention are included within the protection scope of the present invention.

Claims (8)

1. an olefin synthesis method with water as a hydrogen source, it is characterized in that the described olefin synthesis method with water as a hydrogen source is that an alkyne is a synthetic raw material, a cobalt compound is a catalyst, and water is a hydrogen source, by transfer hydrogenation reaction Synthetic olefins. 2 . The olefin synthesis method using water as a hydrogen source according to claim 1 , wherein the olefin synthesis method using water as a hydrogen source comprises a cis olefin synthesis method and a trans olefin synthesis method. 3 . 3. the olefin synthesis method that takes water as hydrogen source according to claim 2 is characterized in that described cis olefin synthesis method comprises the following steps: A. First, the molar ratio of cobalt compound, reducing agent and internal alkyne is 1:(50~70):(10~30) and successively added to the reaction vessel to obtain material a; B. In material a, add methanol whose molar volume ratio (ml: mmol) of cobalt compound is (100~300): 1 and water whose molar volume ratio (μl: mmol) is (3000~4000): 1 in turn The reaction was stirred at a constant temperature at a temperature of 50-70 °C, and the reaction progress was monitored by TLC. After the reaction, the volatile solvent was removed from the reaction solution under reduced pressure, and the target cis olefin was obtained by column chromatography purification. 4. the olefin synthesis method that takes water as hydrogen source according to claim 2 is characterized in that described trans olefin synthesis method comprises the following steps: A. First, the cobalt compound and the ligand are added to the reaction vessel in a molar ratio of 1:(1~1.5), and then the acetonitrile with a molar volume ratio (ml:mmol) of the cobalt compound (50~150):1 is added and stirred 20~40min to get material a after dissolving; B. In the material a, add the reducing agent and internal alkyne with the molar ratio of cobalt compound as 1:(50~70):(10~30) in turn, and then add the molar volume ratio of cobalt compound (ml:mmol) to be (50 ~150): 1 of acetonitrile to obtain material b; C. Add water with a molar volume ratio (μl: mmol) of (3000~4000): 1 to material b, then stir the reaction at a constant temperature at a temperature of 50~70°C, and use TLC to monitor the reaction process. After the reaction, the reaction solution The volatile solvent was removed under reduced pressure and purified by column chromatography to obtain the target trans-olefin. 5. the olefin synthesis method that takes water as hydrogen source according to claim 3 or 4, is characterized in that described cobalt compound is cobalt iodide, cobalt bromide, cobalt chloride, cobalt acetylacetonate, cobalt acetate one or more. 6. the olefin synthesis method that takes water as hydrogen source according to claim 3 or 4, it is characterized in that described reducing agent is one or more in metal elemental zinc powder, manganese powder, magnesium powder or iron powder . 7. the olefin synthesis method that takes water as hydrogen source according to claim 3 or 4, is characterized in that described internal alkyne is diaryl internal alkyne, monoaryl fatty internal alkyne, monoaryl lactyn ester or Fatty alkynes. 8. the olefin synthesis method that takes water as hydrogen source according to claim 4 is characterized in that described part is dppe, dppm, dppp, dppb, dppf, dppen, XantPhos, rac-Binap, 1,10- phen or PPh ₃ .