CN112174782B - Application of metal deuteride/palladium compound catalytic reduction system in deuteration reaction - Google Patents
Application of metal deuteride/palladium compound catalytic reduction system in deuteration reaction Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/128—Halogens; Compounds thereof with iron group metals or platinum group metals
- B01J27/13—Platinum group metals
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
- B01J31/121—Metal hydrides
Abstract
The invention discloses an application of a metal deuteride/palladium compound catalytic reduction system in a deuterization reaction, wherein a palladium compound and a metalate are suspended in a solvent and stirred for 5 minutes under the protection of nitrogen, a deuterization reaction raw material is added, the reaction is carried out for 0.5-36 hours at the temperature of-50-120 ℃, ice water is added for stopping the reaction, the pH value is adjusted to 3.5 by dilute hydrochloric acid, and a reaction solution is subjected to solvent extraction, evaporation to dryness and column chromatography purification to complete the reaction, so that a deuterization product is obtained. In the reduction system of the invention, the hydride and palladium compound catalysts used are readily available reagents in the laboratory, and compared with the existing method, the method is easier to operate and has higher safety.
Description
The invention relates to application of a catalytic reduction system of a metalate/palladium compound in a deallyl reaction and a deuteration reaction, which is a divisional application of the invention with the application date of 2018, 1 month and 30 days and the application number of 201810090551X, and belongs to the technical field of other catalytic systems.
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to application of a metal hydride (deutero) compound/palladium compound catalytic reduction system in a deuteration reaction.
Background
Sodium hydride is a strong base commonly used in laboratories and industry, and is commonly used to dehydrogenate substrates to form the corresponding sodium salt. Although the application history is over 100 years, sodium hydride is rarely used as a reducing agent, and related reports are few. Until recently, several groups reported a new use of sodium hydride as a reducing agent. Such as sodium hydride as a reducing agent to reduce amides to aldehydes, bromobenzene debromination, etc., but here a large excess of sodium hydride is required, and at least 2 equivalents of sodium iodide are required as a promoter; for another example, sodium hydride, catalyzed by 1, 10-phenanthroline, promotes the reduction of aryl halides to hydrogen, where the sodium hydride portion is reacted as a reducing agent and is used in large amounts (3 equivalents).
Disclosure of Invention
The technical problem to be solved by the invention is to provide an application of a metal hydride (deutero) compound/palladium compound catalytic reduction system, thereby providing a new method for deallyl and deuteration reactions and an application of the method in allyl alcohol ester reductive alkylation; this is the first method of using metal activated hydrogen (deuteride) compounds for reduction.
The technical means of the invention for realizing the above-mentioned deallyl and reductive alkylation is to take hydride as a reducing agent and palladium and salts thereof as catalysts to react in a solvent to obtain a deprotected product, a reduced product or a deuterated product. The specific technical scheme is as follows:
the application of a metalate/palladium compound catalytic reduction system in allyl-containing compound deallyl reaction; the metalate is a metal hydride or metal deuteride.
The application of a catalytic reduction system of a metalate/palladium compound in a deuteration reaction raw material deuteration reaction; the metalate is a metal deuteride.
In the present invention, the metal hydride is sodium hydride, lithium hydride, potassium hydride and calcium hydride, preferably sodium hydride and lithium hydride, more preferably sodium hydride.
In the present invention, the metal deuteride is sodium deuteride, lithium deuteride, potassium deuteride and calcium deuteride, preferably sodium deuteride and lithium deuteride, more preferably sodium deuteride.
Sodium hydride as a reducing agent has the following advantages: 1) sodium hydride is industrially prepared by heating hydrogen and metallic sodium, and is cheap and easily available. 2) The use of sodium hydride as a reducing agent is an atom-economical process due to the small molecular weight and simple composition, and the small dosage required in the reaction. 3) When the sodium hydride is used as alkali, the hydride in the sodium hydride is changed into hydrogen to be discharged, which is a waste of resources; when the catalyst is used as a reducing agent, hydride ions enter a product after reaction, so that atoms are economical, and deuterium can be introduced into the product when isotopic sodium deuteride is used for replacing sodium hydride, and the method is very practical.
In the invention, the chemical structural formula of the allyl-containing compound is shown asThe Ar substituent is aryl; r substituents are aryl, alkyl and the like; r1The substituent is allyl or substituted allyl. Preferably, R1The substituent is allyl.
In the present invention, the palladium compound is palladium acetate, palladium chloride, Pd (MeCN)2Cl2、[(η3-C3H5)PdCl]2、Pd(TFA)2、Pd(dppp)Cl2、Pd2(dba)3、Pd(C6H5CN)2Cl2、Pd(OH)2、Pd/C、Pd(PPh3)4、Pd(PPh3)2Cl2Palladium acetate and palladium chloride are preferred, and palladium acetate is more preferred.
In the invention, the molar ratio of the palladium compound, the metalate and the substrate is (0.01-1): (1-5): 1, preferably, the molar ratio of the palladium compound, the metalate and the substrate is (0.03-0.1): (1-2.5): 1, more preferably, the molar ratio of the palladium compound, the metalate and the substrate is 0.06: (1.5-2): 1, most preferably, the molar ratio of the palladium compound, the metalate and the substrate is 0.06: 1.7: 1; the substrate is an allyl-containing compound or a deuterated reaction raw material.
The above technical solution can be expressed as follows:
wherein the Ar substituent is aryl; r substitutionThe radicals are aryl, alkyl, etc.; r1The substituent is allyl or substituted allyl; m is metal such as lithium, sodium, potassium, calcium and the like.
The technical scheme of the invention can be as follows: suspending a palladium compound and a metalate in a solvent under the protection of nitrogen, stirring for 5 minutes, adding a substrate, reacting for 0.5-36 hours at the temperature of-50 ℃ to 120 ℃, adding ice water to stop the reaction, adjusting the pH value to 3.5 by using dilute hydrochloric acid, extracting by using the solvent, evaporating to dryness, and purifying by using column chromatography to finish the reaction to obtain a product, wherein the substrate is an allyl-containing compound or a deuterated reaction raw material.
In the above technical scheme, the solvent is DMA (N, N-dimethylacetamide), DMF, THF, DME, or dioxane.
Preferably, the allyl-containing compound is an aryl allyl ether, an allyl carboxylate; the aryl in the aryl allyl ether is phenyl, naphthyl, substituted phenyl, aromatic heterocycle and the like; the carboxylic acids in the allyl carboxylate are aryl carboxylic acids and fatty carboxylic acids; the allyl groups in the aryl allyl ether and the allyl carboxylate are unsubstituted allyl groups and substituted allyl groups, and the unsubstituted allyl groups are preferred.
In the technical scheme, the deuterated reaction raw materials comprise:
in the technical scheme, the reaction temperature is-50 ℃ to 120 ℃, preferably 10 ℃ to 60 ℃, and more preferably 25 ℃; the reaction time is 0.5 to 36 hours, preferably 1 to 8 hours, more preferably 4 hours.
The invention also discloses a method for the allyl-removing reaction of the allyl-containing compound, which comprises the following steps: suspending a palladium compound and a metalate in a solvent under the protection of nitrogen, stirring for 5 minutes, adding an allyl-containing compound, reacting for 0.5-36 hours at the temperature of-50-120 ℃, adding ice water to stop the reaction, adjusting the pH value to 3.5 by using dilute hydrochloric acid, and performing solvent extraction, evaporation to dryness and column chromatography purification on a reaction solution to finish the reaction.
The invention also discloses a method for carrying out the deuteration reaction by using the deuteration reaction raw material, which comprises the following steps: suspending a palladium compound and a metalate in a solvent under the protection of nitrogen, stirring for 5 minutes, adding a deuteration reaction raw material, reacting for 0.5-36 hours at the temperature of-50-120 ℃, adding ice water to stop the reaction, adjusting the pH value to 3.5 by using dilute hydrochloric acid, and performing solvent extraction, evaporation to dryness and column chromatography purification on a reaction solution to complete the reaction to obtain a deuteration product.
In the technical scheme, the solvent is DMA, DMF, THF, DME or dioxane; the allyl-containing compound is aryl allyl ether or allyl carboxylate; the aryl in the aryl allyl ether is phenyl, naphthyl, substituted phenyl and aromatic heterocycle; the carboxylic acids in the allyl carboxylate are aryl carboxylic acids and fatty carboxylic acids; the allyl groups in the aryl allyl ether and the allyl carboxylate are unsubstituted allyl groups and substituted allyl groups; the deuterated reaction raw material comprises:
the reaction temperature is 10-60 ℃; the reaction time is preferably 1 to 8 hours.
Allyl protection is a frequently used strategy in synthesis, double bonds are isomerized into alkenyl ether by using a palladium catalyst generally, and then the alkenyl ether is removed under an acidic condition, so that two-step operation is relatively complicated; in addition, the catalyst can also be removed by Lewis acid, the reaction condition is more severe, and the functional group tolerance is poor.
The reduction system of the invention is a simple method for removing allyl of phenol and carboxylic acid, the hydride and palladium compound catalyst used are all reagents which are easy to obtain in the laboratory, compared with the existing method, the method is easier to operate, higher in safety, wider in substrate range (no influence on nitryl, aldehyde group, ketone group and double bond), mild in condition and high in reaction yield.
In addition, the present invention is also a good method for introducing deuterium atoms into a substrate.
Detailed Description
Example 1
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 1 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 2 in 99% yield.1H NMR (400 MHz, DMSO-d6): δ 10.10 (br, 1H), 8.13 (d, J = 7.9 Hz, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.51-7.37 (m, 2H), 7.31 (q, J = 8.0 Hz, 2H), 6.87 (d, J = 6.8 Hz, 1H); 13C NMR (151 MHz, DMSO-d6): δ 153.12, 134.38, 127.34, 126.39, 126.04, 124.53, 124.50, 121.94, 118.29, 108.00. LR-MS (ESI): m/z 145.1 [M+H]+。
Example 2
Palladium chloride (0.006 mmol, 2 mol%) and lithium hydride (0.9 mmol, 3 equiv) were suspended in THF (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 1 (0.3 mmol) in THF (0.5 mL) was added, then reacted at 80 ℃ for 1 hour, ice water was added to quench the reaction, pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, combined extracts, dried over sodium sulfate, rotary evaporated to dryness, purified by column chromatography to give product 2 in 92% yield.
Example 3
Under the protection of nitrogen, Pd (MeCN)2Cl2(0.003 mmol, 1 mol%) and potassium hydride (0.3 mmol, 1 equiv) were suspended in DMF (1.0 mL) and stirred at 25 ℃ for 5After the reaction for 36 hours at-50 ℃, a solution of the compound 1 (0.3 mmol) in DMF (0.5 mL) was added, the reaction was stopped by adding ice water, the pH was adjusted to 3.5 with dilute hydrochloric acid, extraction was performed with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purification by column chromatography gave the product 2 with a yield of 84%.
Example 4
Under the protection of nitrogen, Pd2(dba)3(0.3 mmol, 100 mol%) and calcium hydride (1.5 mmol, 5 equiv) were suspended in DME (1.0 mL), stirred at 25 ℃ for 5 minutes, a solution of compound 1 (0.3 mmol) in DME (0.5 mL) was added, then reacted at 120 ℃ for 36 hours, quenched with ice water, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2 in 78% yield.
Example 5
Pd (TFA) under nitrogen protection2(0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in dioxane (1.0 mL), stirred at 25 ℃ for 5 minutes, a solution of compound 1 (0.3 mmol) in dioxane (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 2 in 89% yield.
Example 6
Pd (PPh) under nitrogen protection3)4(0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol)l, 1.7 equiv) was suspended in DMA (1.0 mL), stirred at 25 ℃ for 5 minutes, added with a solution of compound 3 (0.3 mmol) in DMA (0.5 mL), then reacted at 25 ℃ for 4 hours, quenched with ice water, adjusted to pH 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2 in 95% yield.
Example 7
Pd (PPh) under nitrogen protection3)2Cl2(0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL), stirred at 25 ℃ for 5 minutes, a solution of Compound 4 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, quenched with ice water, adjusted to pH 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2 in 92% yield.
Example 8
Under the protection of nitrogen, Pd (OH)2(0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL), stirred at 25 ℃ for 5 minutes, a solution of Compound 5 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, quenched with ice water, adjusted to pH 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2 in 96% yield.
Example 9
Pd/C (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 6 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation and purified by column chromatography to give product 2 in 98% yield.
Example 10
Under the protection of nitrogen, [ (eta ]3-C3H5)PdCl]2(0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL), stirred at 25 ℃ for 5 minutes, a solution of compound 7 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, quenched with ice water, adjusted to pH 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, rotary evaporated to dryness, and purified by column chromatography to give product 2 in 91% yield.
Example 11
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 8 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 50 ℃ for 3 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation and purified by column chromatography to give product 9 in 93% yield.1H NMR (400 MHz, DMSO-d6): δ 8.88 (br, 1H), 6.74 (d, J = 8.9 Hz, 2H), 6.67 (d, J= 8.9 Hz, 2H), 3.65 (s, 3H); 13C NMR (151 MHz, DMSO-d6): δ 152.09, 151.10, 115.69, 114.58, 55.30. LR-MS (ESI): m/z 125.1 [M+H]+。
Example 12
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 10 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 11 in 95% yield.1H NMR: (400 MHz, CDCl3): δ 7.55 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H), 6.75 (br, 1H); 13C NMR (151 MHz, CDCl3): δ 160.41, 134.46, 119.39, 116.61, 103.06. LR-MS (ESI): m/z 120.0 [M+H]+。
Example 13
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 12 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation and purified by column chromatography to give product 13 in 96% yield.1H NMR (400 MHz, CDCl3): δ 9.86 (s, 1H), 7.82 (d, J = 8.3 Hz, 2H), 6.99 (d, J= 8.3 Hz, 2H); 13C NMR (151 MHz, CDCl3): δ 191.42, 161.85, 132.67, 129.93, 116.16. LR-MS (ESI): m/z 123.0 [M+H]+。
Example 14
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 14 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give 15 in 93% yield.1H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 8.5 Hz, 2H), 6.96 (d, J = 8.5 Hz, 2H), 2.59 (s, 3H); 13C NMR (151 MHz, CDCl3): δ 198.86, 161.58, 131.38, 129.64, 115.70, 26.44. LR-MS (ESI): m/z 137.1 [M+H]+。
Example 15
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 16 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 10 ℃ for 8 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation and purified by column chromatography to give product 17 in 92% yield.1H NMR (400 MHz, CDCl3): δ 10.59 (br, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 6.99 (t, J = 7.8 Hz, 1H); 13C NMR (151 MHz, CDCl3): δ 155.26, 137.67, 133.84, 125.21, 120.35, 120.11. LR-MS (ESI): m/z 140.0 [M+H]+。
Example 16
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 18 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation and purified by column chromatography to give 19% yield 97%.1H NMR (400 MHz, CDCl3): δ 7.56-7.46 (m, 3H), 7.40-7.30 (m, 3H), 7.25 (m, 1H), 7.17-7.05 (m, 2H), 6.94 (m, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.00 (s, 1H); 13C NMR (151 MHz, CDCl3): δ 153.05, 137.69, 130.32, 128.79, 127.75, 127.36, 126.68, 124.82, 123.09, 121.32, 116.07. LR-MS (ESI): m/z 197.0 [M+H]+。
Example 17
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 20 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation and purified by column chromatography to give product 21 in 93% yield.1H NMR (400 MHz, DMSO-d6): δ 12.26 (br, 1H), 8.16-8.04 (m, 2H), 7.81 (t, J = 7.5 Hz, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H); 13C NMR (151 MHz, DMSO-d6): δ 160.73, 148.69, 145.39, 134.30, 127.16, 126.72, 125.81, 122.61. LR-MS (ESI): m/z 147.0 [M+H]+。
Example 18
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 22 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 23 in 97% yield.1H NMR (400 MHz, CDCl3): δ 7.10 (t, J = 7.9 Hz, 1H), 7.00-6.94 (m, 2H), 6.58-6.52 (m, 2H), 5.31 (br, 1H), 3.77 (s, 3H); 13C NMR (151 MHz, CDCl3): δ 149.08, 138.80, 127.80, 122.60, 118.02, 103.92, 102.61, 97.16, 33.25. LR-MS (ESI): m/z 147.9 [M+H]+。
Example 19
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 24 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 25 in 97% yield.1H NMR (400 MHz, DMSO-d 6 ): δ 12.08 (br, 1H), 7.74 (d, J = 8.3 Hz, 2H), 6.68 (d, J = 8.3 Hz, 2H), 2.97 (s, 6H); 13C NMR (151 MHz, DMSO-d 6 ): δ 167.51, 153.06, 130.90, 116.92, 110.74, 39.62. LR-MS (ESI): m/z 166.1 [M+H]+。
Example 20
Nitrogen gasPalladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under protection, stirred at 25 ℃ for 5 minutes, a solution of compound 26 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 27 in 95% yield.1H NMR (400 MHz, CDCl3): δ 8.04 (m, 1H), 7.61 (m, 1H), 7.26 (m, 1H), 7.19 (m, 1H); 13C NMR (151 MHz, CDCl3):δ 169.93 (d, J = 3.0 Hz), 162.79 (d, J = 262.1 Hz), 135.77 (d, J = 9.2 Hz), 132.91, 124.25 (d, J = 3.9 Hz), 117.70 (d, J = 9.0 Hz), 117.32 (d, J = 22.2 Hz). LR-MS (ESI): m/z 141.0 [M+H]+。
Example 21
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 28 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation and purified by column chromatography to give product 29 in 93% yield.1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 7.0 Hz, 1H), 7.63 (s, 1H), 7.39 (t, J= 7.5 Hz, 1H), 7.17 (d, J = 7.2 Hz, 1H), 3.88 (s, 3H); 13C NMR (151 MHz, CDCl3): δ 172.33, 159.75, 130.71, 129.67, 122.84, 120.64, 114.55, 55.61. LR-MS (ESI): m/z 153.0 [M+H]+。
Example 22
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 30 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 31 in 95% yield.1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 7.6 Hz, 1H), 7.46 (t, J = 7.0 Hz, 1H), 7.36-7.26 (m, 2H), 2.68 (s, 3H); 13C NMR (151 MHz, CDCl3): δ 173.51, 141.36, 132.94, 131.91, 131.58, 128.31, 125.84, 22.11. LR-MS (ESI): m/z 137.0 [M+H]+。
Example 23
Palladium acetate (0.018 mmol, 6 mol%) and sodium hydride (60% in oil, 0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, stirred at 25 ℃ for 5 minutes, a solution of compound 32 (0.3 mmol) in DMA (0.5 mL) was added, then reacted at 25 ℃ for 4 hours, ice water was added to quench the reaction, the pH was adjusted to 3.5 with dilute hydrochloric acid, extracted with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation and purified by column chromatography to give product 33 in 97% yield.1H NMR (400 MHz, CDCl3): δ 9.43 (br, 1H), 7.37-7.26 (m, 5H), 5.21-5.13 (m, 2H), 4.44-4.37 (m, 1H), 3.60-3.46 (m, 2H), 2.27-2.10 (m, 2H), 1.96-1.91 (m, 2H); LR-MS (ESI): m/z 250.1 [M+H]+。
Example 24
Palladium acetate (0.018 mmol, 6 mol%) and sodium deuteride (0.51 mmol, 1.7 equiv) were suspended in DMA (1.0 mL) under nitrogen, and stirred at 25 ℃ for 5 minutesThen, a solution of compound 34 (0.3 mmol) in DMA (0.5 mL) was added, followed by reaction at 25 ℃ for 4 hours, ice water was added to quench the reaction, extraction was performed with ethyl acetate, the combined extracts were dried over sodium sulfate, evaporated to dryness by rotary evaporation, and purified by column chromatography to give product 35 with a yield of 95%.1H NMR (400 MHz, CDCl3): δ 7.43 (d, J = 7.2 Hz, 1H), 7.19 (t, J = 7.4 Hz, 1H), 6.91 (t, J = 7.0 Hz, 1H), 6.86 (d, J = 7.9 Hz, 1H), 6.71 (d, J = 15.9 Hz, 1H), 6.30-6.15 (m, 1H), 3.85 (s, 3H), 2.23 (m, 1H), 1.48 (m, 2H), 1.34 (m, 4H), 0.91 (m, 3H); 13C NMR (151 MHz, CDCl3): δ 156.39, 132.14, 127.87, 127.20, 126.50, 124.31, 120.77, 110.94, 55.62, 33.62, 31.66, 29.36, 22.73, 14.23. LR-MS (ESI): m/z 206.2 [M+H]+。
Claims (5)
1. The application of a metal deuteride/palladium compound catalytic reduction system in deuteration reaction; the metal deuteride is sodium deuteride; the deuterated reaction raw material comprises:
the palladium compound is palladium acetate, palladium chloride, Pd (MeCN)2Cl2、[(η3-C3H5)PdCl]2、Pd(TFA)2、Pd(dppp)Cl2、Pd2(dba)3、Pd(C6H5CN)2Cl2、Pd(OH)2、Pd/C、Pd(PPh3)4、Pd(PPh3)2Cl2One kind of (1).
2. The use of the metal deuteride/palladium compound catalytic reduction system of claim 1, wherein the deuterization reaction is performed at 10-60 ℃ for 1-8 hours.
3. The use of the metal deuteride/palladium compound catalytic reduction system in a deuteration reaction according to claim 1, wherein the molar ratio of the palladium compound, the metal deuteride and the deuteration reaction raw material is (0.03-0.1) to (1-2.5) to 1.
4. The use of the metal deuteride/palladium compound catalytic reduction system in deuteration reaction as in claim 3, wherein the molar ratio of the palladium compound, the metal deuteride and the deuteration reaction raw material is 0.06: 1.7: 1.
5. The use of the metal deuteride/palladium compound catalytic reduction system according to claim 1 in deuteration, wherein deuteration comprises the steps of: under the protection of nitrogen, suspending a palladium compound and a metal deuteride in a solvent, stirring, adding a deuterion reaction raw material, and reacting at-50-120 ℃ for 0.5-36 hours to obtain a deuterion product.
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