CN114574883A - Method for deoxidizing, hydrogenating and deuterating alpha, beta-unsaturated aldehyde ketone into corresponding olefin and deuterated olefin - Google Patents
Method for deoxidizing, hydrogenating and deuterating alpha, beta-unsaturated aldehyde ketone into corresponding olefin and deuterated olefin Download PDFInfo
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Abstract
The invention discloses a synthesis method for deoxidizing, hydrogenating and deuterating alpha, beta-unsaturated aldehyde ketone compounds into corresponding olefins and deuterated olefins under electrochemical conditions, and relates to the technical field of drug synthesis. The synthesis method comprises the following steps: in an electrochemical reaction tank, alpha, beta-unsaturated aldehyde ketone, electrolyte and protonic acid or deuterated protonic acid are dissolved in a solvent, electrodes are connected, and the alpha, beta-unsaturated aldehyde ketone compound can be reduced into corresponding olefin or deuterated olefin compound by electrifying reaction at room temperature, wherein the position of the carbon-carbon double bond of the olefin is moved from the original alpha, beta-position to the original carbonyl carbon atom and alpha-position thereof. The method can be widely applied to synthesis of corresponding medicines and deuterated medicines.
Description
Technical Field
The invention relates to the technical field of drug synthesis, in particular to a novel synthesis method for preparing corresponding olefin and deuterated olefin by deoxidizing, hydrogenating and deuterating alpha, beta-unsaturated aldehyde ketone under electrochemical conditions, wherein the position of an olefin carbon-carbon double bond is moved from the original alpha, beta-position to the original carbonyl carbon atom and alpha-position thereof.
Background
In the history of drug synthesis, the alpha, beta-unsaturated aldehyde ketone compound is efficiently reduced to corresponding olefin in a green way, which is a synthesis method with extremely high value and is widely applied to the synthesis of a large number of drugs.
The literature reports that the existing methods for deoxidizing and reducing alpha, beta-unsaturated aldehyde ketone into olefin are as follows:
(1) climensen reduction (2019, CN 110028544; 2016, CN105237606)
The disadvantages are as follows: the method needs to use highly toxic zinc amalgam, which can cause serious mercury pollution to the environment; in addition, with the increasing tension of mercury sources in recent years, the cost is higher and higher;
(2) Wolff-Kishner-Huang Minlon reduction (2017, CN104861034)
The disadvantages are as follows: the method has high reaction temperature (180-200 ℃) and needs a large amount of strong alkali, so that a plurality of substrates sensitive to alkali and high temperature are limited; in addition, the method uses a large amount of hydrazine and has low atom utilization rate.
(3) Multi-step synthesis (Journal of Chemical Research, Miniprint,1989,2,401-428)
The results of a literature search show that Hoffmann Joachim et al reported an example of the conversion of cyclohexenone to an olefin-displaced cyclohexene. The conversion is carried out in three steps, and particularly, the electrochemical reduction deoxidation in the last step is remarkable in that an expensive platinum electrode is required, and the yield is only 5%.
Furthermore, the deuterated compound refers to a compound obtained by reacting a hydrogen atom in a certain C-H bond or certain C-H bonds in the molecule of the compound: (1H) Replacement by deuterium atom (D or2H) In that respect Deuterium atom (D or2H) And a hydrogen atom (1H) Is an isotope, has the same number of protons, is a neutron and an electron. Since the C-D bond has larger bond energy, the breaking of the C-D bond requires higher energy than the breaking of the C-H bond, and the breaking of the carbon-hydrogen bond is often an important step in the metabolic process of organic molecules. Therefore, replacing the C-H bond in a drug molecule with a more difficult to break C-D bond generally reduces the rate of drug metabolism.
Compared with a drug molecule which is not modified by a deuterium atom, a deuterated drug generally has the following advantages: prolonging the half-life period of the medicine; the dosage or frequency of taking the medicine is reduced, and the compliance of patients is improved; thirdly, certain metabolic sites can be blocked, the generation of toxic metabolites is reduced, and the toxicity of the medicine is reduced; and fourthly, the isomerization of some medicines in the body can be prevented from losing the medicinal activity and even generating toxicity.
At present, the methods for synthesizing deuterated drugs mainly include chemical synthesis methods and hydrogen-deuterium exchange methods, and commonly used deuterium sources include deuterium gas, deuterated water, deuterated iodomethane, deuterated methanol, deuterated ethanol, deuterated benzene, deuterated lithium aluminum and the like, which are specifically described below:
(1) chemical synthesis method
The most common deuterated group in deuterated drugs is a heteroatom having a deuterated methyl (-CD) attached thereto3) Or deuterated ethyl (-CD)2CD3) For this structure, deuterated iodomethane (CD) is typically used3I) Or deuterated iodoethane (CD)3CD2I) Etc. to produce the corresponding deuterated product. Such as the synthesis of the drug deuterated agomelatine.
For deuterium atom bondingThe target compound is obtained through multi-step reactions by using deuterated benzene or derivatives thereof (such as deuterated bromobenzene, deuterated aniline, deuterated benzoic acid and the like) as a substrate on a drug molecule on a benzene ring. Such as the drug deuterodilarox (deferasirox-d)4) And (4) synthesizing.
When the drug synthesis route contains reduction reaction, the unsaturated bond can be reduced by using a reducing deuteration reagent (such as deuterium gas, lithium aluminum deuterate and the like) so as to obtain a product of deuterium atom added on the unsaturated bond and further obtain a target deuteration drug molecule, in addition, for a compound containing a carbon-halogen bond, reduction dehalogenation can be carried out under the catalysis of Pd/C, and if the deuterium gas is used as a deuterium source, a product of which the halogen is replaced by deuterium can be obtained, such as a drug deuteration nevirapine (nevirapine-d)1) And (4) synthesizing.
The chemical synthesis method has the disadvantages of multiple synthesis steps, low yield and easy occurrence of the phenomena of transfer of deuteron sites and deuteron removal in subsequent reactions; furthermore, the deuterated reagents used are generally expensive, and the deuterated sites are limited by the type of deuterated reagents, making it difficult to prepare deuterated compounds of complex natural products and polymers.
(2) Hydrogen deuterium exchange method
The C-H bond at the ortho position of the carbonyl group has stronger acidity and can generate hydrogen and deuterium exchange reaction with deuterated water under the action of alkali. Such as the synthesis of CTP-499 as a therapeutic agent of diabetic nephropathy.
The C-H bond of the end alkyne also has certain acidity, and can also generate hydrogen and deuterium exchange reaction with a deuterated solvent under the catalysis of alkali or metalFor example, the drug deutero-phenthoate (Edudatin-d)1) And (4) synthesizing.
In summary, the existing methods for deoxidizing and reducing α, β -unsaturated aldehyde ketone into corresponding olefin and synthesizing deuterated compound all have obvious disadvantages and need to be improved. In particular, the deoxidation, hydrogenation and deuteration of α, β -unsaturated aldehyde ketones to the corresponding olefins and deuterated olefins not only requires a multi-step synthesis, but also has extremely low conversion. Therefore, improvement of such transformation is urgently required.
Disclosure of Invention
The invention aims to create a novel, green, safe and low-cost method for deoxidizing, hydrogenating or deuterating alpha, beta-unsaturated aldehyde ketone into corresponding olefin and deuterated olefin compounds, and the position of the carbon-carbon double bond of the olefin is moved from the original alpha, beta-position to the original carbonyl carbon atom and alpha-position thereof.
In order to improve the existing method, the invention designs a method for deoxidizing, hydrogenating and deuterating alpha, beta-unsaturated aldehyde ketone into corresponding olefin and deuterated olefin compounds under electrochemical conditions. The method comprises the following steps: in an electrochemical reaction pool, alpha, beta-unsaturated aldehyde ketone, electrolyte and protonic acid or deuterated protonic acid are dissolved in a solvent, and the alpha, beta-unsaturated aldehyde ketone compound is deoxidized, hydrogenated or deuterated and reduced into corresponding olefin or deuterated olefin compound by electrifying reaction at room temperature, and the position of the carbon-carbon double bond of the olefin is moved from the original alpha, beta-position to the original carbonyl carbon atom and alpha-position thereof. The specific synthetic method is shown as the following formula:
or:
the invention has the beneficial effects that: compared with the existing synthesis process, the method is green, safe, economical, simple and convenient, and does not need to use highly toxic metal (such as mercury); noble metals (such as palladium and platinum) are not needed; high temperature and high pressure conditions are not needed; and the method can be used for large-scale production, so that the method disclosed by the invention can be widely applied to industrial production.
The invention provides a new method for deoxidizing, hydrogenating, deuterating and reducing alpha, beta-unsaturated aldehyde ketone into corresponding olefin and deuterated olefin compound, which is green, efficient, safe and low in consumption, and the position of the carbon-carbon double bond of the olefin is moved from the original alpha, beta-position to the original carbonyl carbon atom and alpha-position thereof. The method comprises the following steps:
dissolving an alpha, beta-unsaturated aldehyde ketone compound, an electrolyte and protonic acid or deuterated protonic acid in a solvent in an electrochemical reaction tank, connecting electrodes, electrifying at room temperature for reaction, monitoring the reaction process, powering off and stopping stirring after the reaction is finished, distilling under reduced pressure to recover the solvent, extracting by using dichloromethane and water, combining organic phases, drying by using anhydrous sodium sulfate or magnesium sulfate, filtering, concentrating, and carrying out column chromatography or reduced pressure distillation on residues to obtain the product.
Detailed description of the preferred embodiments
The process of the present invention will be further illustrated by the following examples, but the present invention is not limited to these examples.
Example 1:
collecting adrenal sterone (150mg, 0.5mmol, 1.0eq.), NaCl (58.4mg, 1.0mmol, 2.0eq.) in a 10mL three-necked flask; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was dissolved with stirring; hydrochloric acid (36%) (0.4mL, 10.0eq.), HCOOH (0.15mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extracted with DCM (3X 5mL) and combined withThe organic phase was dried over anhydrous sodium sulfate, filtered and the residue after distillation to recover the solvent was purified by column chromatography to give the product (78%).
Example 2:
taking adrenosterone (150mg, 0.5mmol, 1.0eq.), NaCl (58.4mg, 1.0mmol, 2.0eq.) in a 10mL three-necked flask; adding CH3CN(8.0mL)，D2O (1.0mL), DCM (2.0mL) was dissolved with stirring; deuterated hydrochloric acid (DCl, 20 wt.% in D) was added2O) (0.78mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extracted with DCM (3X 5mL), combined organic phases, dried over anhydrous sodium sulfate, filtered, and the residue after distillation to recover the solvent was purified by column chromatography to give the product (82%, deuteration rate)>99％)。
Example 3:
taking adrenosterone (150mg, 0.5mmol, 1.0eq.), NaCl (5.8mg, 0.1mmol, 0.2 eq.) in a 10mL three-necked bottle; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was stirred to dissolve; hydrochloric acid (36%) (0.4mL, 10.0eq.), HCOOH (0.15mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extracted with DCM (3 × 5mL), the combined organic phases dried over anhydrous sodium sulfate, filtered and the residue after distillation to recover the solvent was purified by column chromatography to give the product (44%).
Example 4:
taking adrenalone (150mg, 0.5mmol, 1.0eq.), NaCl (584.4mg, 10mmol, 20eq.) in a 10mL three-necked bottle; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was dissolved with stirring; hydrochloric acid (36%) (0.4mL, 10.0eq.), HCOOH (0.15mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extraction with DCM (3 × 5mL), combination of the organic phases, drying over anhydrous sodium sulphate, filtration and purification by column chromatography of the residue after recovery of the solvent by distillation gave the product (90%).
Example 5:
taking progesterone (157mg, 0.5mmol, 1.0eq.), NaCl (58.4mg, 1.0mmol, 2.0eq.) and placing in a 10mL three-neck bottle; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was dissolved with stirring; hydrochloric acid (36%) (0.4mL, 10.0eq.), HCOOH (0.15mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extracted with DCM (3X 5mL), the organic phases were combined, dried over anhydrous sodium sulfate, filtered and the residue after distillation to recover the solvent was purified by column chromatography to give the product (85%).
Example 6:
placing androstenedione (143mg, 0.5mmol, 1.0eq.), NaCl (58.4mg, 1.0mmol, 2.0eq.) in a 10mL three-necked flask; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was dissolved with stirring; hydrochloric acid (36%) (0.4mL, 10 was added.0eq.), HCOOH (0.15mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extracted with DCM (3 × 5mL), the combined organic phases dried over anhydrous sodium sulfate, filtered and the residue after distillation to recover the solvent was purified by column chromatography to give the product (80%).
Example 7:
taking androstenedione (14.3mg, 0.05mmol, 0.10eq.), NaCl (58.4mg, 1.0mmol, 2.0eq.) in a 10mL three-necked bottle; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was dissolved with stirring; hydrochloric acid (36%) (0.4mL, 10.0eq.), HCOOH (0.15mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, and a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extraction with DCM (3 × 5mL), combination of the organic phases, drying over anhydrous sodium sulphate, filtration and purification by column chromatography of the residue after recovery of the solvent by distillation gave the product (92%).
Example 8:
taking androstenedione (1430mg, 5mmol, 10eq.), NaCl (58.4mg, 1.0mmol, 2.0eq.) in a 10mL three-necked bottle; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was dissolved with stirring; hydrochloric acid (36%) (0.4mL, 10.0eq.), HCOOH (0.15mL, 10.0 eq.); an electrode (an anode is a metal zinc rod, a cathode is a graphite felt sheet) is inserted into a three-necked flask, and the three-necked flask is electrified and reacts for about 3 hours at a constant current of 500 mA. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extracted with DCM (3X 5mL), the organic phases combined, dried over anhydrous sodium sulfate, filtered and the residue after recovery of the solvent by distillationPurification by column chromatography gave the product (38%).
Example 9:
taking the compound 3-biphenyl cyclohexene-1-one (124mg, 0.5mmol, 1.0eq.), NaCl (58.4mg, 1.0mmol, 2.0eq.) in a 10mL three-neck bottle; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was dissolved with stirring; hydrochloric acid (36%) (0.4mL, 10.0eq.), HCOOH (0.15mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, and a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extraction with DCM (3 × 5mL), combination of the organic phases, drying over anhydrous sodium sulphate, filtration and purification of the residue after distillation of the solvent by column chromatography gave the product in 82% yield.
Example 10:
taking the compound 3-p-chlorophenyl cyclohexen-1-one (103mg, 0.5mmol, 1.0eq.), NaCl (58.4mg, 1.0mmol, 2.0eq.) in a 10mL three-necked flask; adding CH3CN(8.0mL)，H2O (1.0mL), DCM (2.0mL) was dissolved with stirring; hydrochloric acid (36%) (0.4mL, 10.0eq.), HCOOH (0.15mL, 10.0 eq.); inserting an electrode (an anode is a metal zinc rod, a cathode is a graphite felt sheet) into a three-necked flask, electrifying, and carrying out 30mA constant current reaction for about 3 h. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (10mL), extracted with DCM (3 × 5mL), the combined organic phases dried over anhydrous sodium sulfate, filtered and the residue after distillation to recover the solvent was purified by column chromatography to give the product in about 87% yield.
Example 11:
take adrenosterone (15.0g, 50mmol, 1.0eq), NaCl (5.84g, 100mmol, 2.0eq) in a 2L beaker; adding CH3CN(800mL)，H2O (100mL), DCM (200mL) was stirred to dissolve; hydrochloric acid (36%) (43.0mL, 10.0eq), HCOOH (14.9mL, 10.0eq) was added; electrodes (an anode is a zinc bar, a cathode is a graphite felt sheet) are respectively inserted into the beakers, and the beakers are electrified and react for about 10 hours at a constant current of 300 mA. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (200mL), extracted with DCM (3X 100mL), the organic phases were combined, dried over anhydrous sodium sulfate, filtered and the residue after evaporation of the solvent was purified by column chromatography to give the product (92%).
Example 12:
glycyrrhetinic acid (456.7g, 1.0mol, 1.0eq), NaCl (116.9g, 2.0mol, 2.0eq) were put in a 10L reactor; adding CH3CN(1L)，H2O (150mL), DCM (200mL) was stirred to dissolve; hydrochloric acid (36%) (429.6mL, 5.0eq), HCOOH (149mL, 5.0eq) was added; electrodes (an anode is a zinc rod and a cathode is a graphite felt sheet) are respectively inserted into the beakers, and the beakers are electrified and subjected to 20A constant current reaction for about 5 hours. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (200mL), extracted with DCM (3X 200mL), the organic phases were combined, dried over anhydrous sodium sulfate, filtered and the residue after evaporation of the solvent was purified by column chromatography to give the product (90%).
Example 13:
putting progesterone (314.5g, 1.0mol, 1.0eq) and NaCl (116.9g, 2.0mol, 2.0eq) in a 10-liter reaction kettle; adding CH3CN(1L)，D2O (150mL), DCM (200mL) was stirred to dissolve; deuterated hydrochloric acid (DCl, 20 wt.% in D) was added2O) (781.2mL, 5.0 eq.); respectively inserted into the beakersAnd electrifying an electrode (the anode is a zinc rod, and the cathode is a graphite felt sheet), and carrying out 10A constant current reaction for about 10 hours. After the reaction is completed, the solvent is recovered by distillation, and H is added2O (200mL), extraction with DCM (3X 200mL), combination of the organic phases, drying over anhydrous sodium sulfate, filtration, and purification by column chromatography of the residue after removal of the solvent to give the product (88%, deuteration rate)>99％)。
TABLE-1 general yields of the dehydroxyreduction of α, β -unsaturated aldoketones under various conditions (electrochemical dehydroxyreduction of progesterone is exemplified) (the present invention is not limited to the reaction conditions listed in the Table)
And (4) surface note: the amount of substance of progesterone in the table is 1.0 millimolar; hydrochloric acid is 36%; the dimensions of the rod-shaped electrode are as follows: the diameter is 0.8cm, and the length is 10 cm; the length, width and height of the graphite felt are as follows: 2cm × 1cm × 0.5 cm; DCM is dichloromethane; TMAF is tetramethylammonium fluoride; TEAC is tetraethylammonium chloride; TEABF4Is tetraethylammonium tetrafluoroborate; TEAPF6Tetraethylammonium hexafluorophosphate; DMF is N, N-dimethylformamide.
TABLE-2 general yields of the deoxydeuteration of α, β -unsaturated aldoketones under various conditions (taking the electrochemical deoxydeuteration of norgestrel as an example) (the invention is not limited to the reaction conditions listed in the Table)
And (4) surface note: the amount of norgestrel species in the table was 1.0 millimolar; deuterated hydrochloric acid is 20 wt.% in D2O; the dimensions of the rod-shaped electrode are as follows: the diameter is 0.8cm, and the length is 10 cm; the length, width and height of the graphite felt are as follows: 2cm × 1cm × 0.5 cm; TMAF is tetramethylammonium fluoride; TEAC is tetraethylammonium chloride; TEABF4Is tetraethylammonium tetrafluoroborate; TEAPF6Tetraethylammonium hexafluorophosphate; DMF is N, N-dimethylformamide.
Appendix-3 Deoxyhydroreduction of alpha, beta-unsaturated aldehyde ketone substrates and selection of the yields (not restricted to these substrates) examined by the invention
And (4) surface note: the yields in this table are isolated yields obtained according to the reaction conditions in example 4.
TABLE-4 Deoxydeutralization of products of alpha, beta-unsaturated aldehyde ketones and their yield and deuteration data for the investigation of the invention (not limited to these substrates)
And (4) surface note: the yields in this table are the isolated yields obtained according to the reaction conditions in example 2, the deuteration rates are determined by nmr spectroscopy, and the numbers in the table indicate: (yield, deuteration rate).
Claims (11)
1. A method for deoxidizing, hydrogenating and deuterating alpha, beta-unsaturated aldehyde ketone into corresponding olefin and deuterated olefin is characterized in that in an electrochemical reaction cell, the alpha, beta-unsaturated aldehyde ketone, electrolyte and protonic acid or deuterated protonic acid are dissolved in a solvent, electrodes are connected, and the alpha, beta-unsaturated aldehyde ketone compound can be reduced into corresponding olefin or deuterated olefin compound by electrifying reaction at room temperature, and the position of the carbon-carbon double bond of the olefin is moved from the original alpha, beta-position to the original carbonyl carbon atom and alpha-position thereof, wherein,
the electrode is characterized in that: the anode material is one or alloy of zinc, magnesium, aluminum, tin, iron, manganese, nickel, copper, lead, cobalt or titanium;
the cathode material is one or an alloy of carbon or graphite felt or glassy carbon or zinc or magnesium or aluminum or tin or iron or manganese or nickel or copper or lead or cobalt or steel or silver or platinum or mercury or chromium or titanium;
the electrolyte is as follows: salts of cations with anions;
the protonic acid is: one or a mixture of two or more of sulfuric acid, phosphoric acid, hydrochloric acid, acetic acid, trifluoroacetic acid, formic acid, benzoic acid, benzenesulfonic acid, p-toluenesulfonic acid and nitric acid;
the deuterated protonic acid is as follows: one or a mixture of two or more of deuterated sulfuric acid, deuterated phosphoric acid, deuterated hydrochloric acid, deuterated acetic acid, deuterated trifluoroacetic acid, deuterated formic acid, deuterated benzoic acid, deuterated benzenesulfonic acid, deuterated p-toluenesulfonic acid and deuterated nitric acid;
α, β -unsaturated aldehyde ketone: the mass ratio of the protonic acid or deuterated protonic acid is 1: (0.1-1000).
2. The method of claim 1, wherein the electrochemical reaction cell is a divided cell or a non-divided cell.
3. The deoxygenation hydrogenation and deuteration reduction of α, β -unsaturated aldehyde ketones to the corresponding olefins and deuterated olefins according to claim 1, wherein the solvent is one or a mixture of two or more of acetonitrile, deuterated acetonitrile, Dichloromethane (DCM), deuterated dichloromethane, Dichloroethane (DCE), deuterated dichloroethane, chloroform, deuterated chloroform, carbon tetrachloride, N-Dimethylformamide (DMF), 1, 4-dioxane, methanol, deuterated methanol, ethanol, deuterated ethanol, isopropanol, hexafluoroisopropanol, acetone, deuterated acetone, dimethyl sulfoxide (DMSO), deuterated dimethyl sulfoxide, tetrahydrofuran, water, and deuterated water.
4. The method of claim 1, wherein the α, β -unsaturated aldehyde-ketone is a compound of formula (1), the olefin product of deoxyhydrogenation is a compound of formula (2), and the deuterated olefin product of deoxydeuteration is a compound of formula (3):
wherein R and R' are hydrogen or aryl or heterocyclic aryl or alkyl or cycloalkyl or alkyl or aryl with halogen, oxygen, nitrogen, silicon, phosphorus, sulfur atoms; or R and R' are linked together to form an alicyclic or aromatic ring compound; n is a positive integer of 0, 1-11, wherein the product is olefin or deuterated olefin, and the position of the carbon-carbon double bond of the olefin is moved from the original alpha, beta-position to the original carbonyl carbon atom and alpha-position thereof.
5. The method of claim 1, wherein the electrode, anode, is one or two or more of zinc, magnesium, aluminum, tin, iron, manganese, nickel, copper, lead, cobalt, titanium, alloy or foam metal; the cathode is carbon or graphite felt or glassy carbon or one or two or more of metal zinc, magnesium, aluminum, tin, iron, manganese, nickel, copper, lead, cobalt, silver, steel, platinum, mercury, chromium and titanium alloy or foam metal.
6. The method of deoxygenation hydrogenation and deuteration reduction of α, β -unsaturated aldehyde ketones to the corresponding olefins and deuterated olefins according to any one of claims 1 to 5, wherein said electrodes are in the shape of sheets or blocks or rods or nets.
7. The process for the deoxygenation, hydrogenation, and deuteration of an α, β -unsaturated aldehyde ketone to the corresponding alkene and deuterated alkene as in any one of claims 1 to 5, wherein the electrolyte is a salt of one or two or more cations with one or two or more anions; the cation mentioned herein is lithium ion, sodium ion, potassium ion, magnesium ion, calcium ion, zinc ion, iron ion (divalent or trivalent), copper ion (monovalent or divalent), cobalt ion, titanium ion (trivalent or tetravalent), manganese ion (divalent or tetravalent), nickel ion (divalent), ammonium group (NH)4 +) Tetraalkylammonium radical (R)4N+) At least one of; the alkyl is at least one of methyl, ethyl, propyl, isopropyl, butyl and n-hexadecyl; the anion mentioned here is fluorine anion, chlorine anion, bromine anion, iodine anion, perchloric acid anion, tetrafluoroboric acid anion, hexafluorophosphoric acid anionAt least one of p-toluenesulfonic acid negative ions, benzenesulfonic acid negative ions, methanesulfonic acid negative ions, acetic acid negative ions, benzoic acid negative ions, carbonate radicals, bicarbonate radicals, nitrate radicals, nitrite radicals, phosphate radicals, hydrogen phosphate radicals, dihydrogen phosphate radicals, sulfate radicals and hydrogen sulfate radicals.
8. The process for the deoxygenation, hydrogenation and deuteration reduction of α, β -unsaturated aldehyde ketones to the corresponding olefins and deuterated olefins according to any one of claims 1 to 5, wherein the ratio of the amounts of the α, β -unsaturated aldehyde ketone compound and the protic or deuterated protic acid species is: the alpha, beta-unsaturated aldehyde ketone compound is a protonic acid or deuterated protonic acid 1 (0.1-1000).
9. The method for the deoxygenation, hydrogenation and deuteration of α, β -unsaturated aldehyde ketone into corresponding olefin and deuterated olefin according to any of claims 1 to 5, wherein the electrochemical reaction is powered by a constant current or a constant voltage, and the current intensity is 1 mA-20A; the reaction temperature is-30 to 100 ℃.
10. The method of deoxygenation, hydrogenation and deuteration of α, β -unsaturated aldehyde ketones to the corresponding olefins and deuterated olefins according to any of claims 1 to 5, wherein the molar concentration of the electrolyte is 0.01 to 100 mol/L.
11. The method of deoxygenation hydrogenation and deuteration reduction of α, β -unsaturated aldehyde ketones to the corresponding olefins and deuterated olefins according to any of claims 1 to 5, wherein the molar concentration of α, β -unsaturated aldehyde ketones is 0.01 to 100 mol/L.
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| US4082627A (en) * | 1977-05-26 | 1978-04-04 | Eli Lilly And Company | Electrolytic reduction of dihydrobenzopyranoxanthenones |
| DE19709870A1 (en) * | 1996-03-28 | 1997-10-30 | Knoell Hans Forschung Ev | New 17-substituted 16 alpha ,17 alpha -carbocyclic steroid compounds |
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| US20140110268A1 (en) * | 2012-10-24 | 2014-04-24 | Board Of Trustees Of Michigan State University | Electrocatalytic hydrogenation and hydrodeoxygenation of oxygenated and unsaturated organic compounds |
| US20150008139A1 (en) * | 2012-03-06 | 2015-01-08 | Board Of Trustees Of Michigan State University | Electrocatalytic Hydrogenation and Hydrodeoxygenation of Oxygenated and Unsaturated Organic Compounds |
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