CN111635300A - Method for preparing deuterated benzoin by using deuterium source as deuterium source - Google Patents
Method for preparing deuterated benzoin by using deuterium source as deuterium source Download PDFInfo
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- CN111635300A CN111635300A CN202010619537.1A CN202010619537A CN111635300A CN 111635300 A CN111635300 A CN 111635300A CN 202010619537 A CN202010619537 A CN 202010619537A CN 111635300 A CN111635300 A CN 111635300A
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- deuterium
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- 229910052805 deuterium Inorganic materials 0.000 title claims abstract description 46
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 title claims abstract description 45
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical class C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 46
- -1 benzil compound Chemical class 0.000 claims abstract description 32
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 239000002841 Lewis acid Substances 0.000 claims abstract description 10
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 10
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052802 copper Inorganic materials 0.000 claims description 3
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 229910052748 manganese Inorganic materials 0.000 claims description 3
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 238000011161 development Methods 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 5
- 244000028419 Styrax benzoin Species 0.000 abstract description 3
- 235000000126 Styrax benzoin Nutrition 0.000 abstract description 3
- 235000008411 Sumatra benzointree Nutrition 0.000 abstract description 3
- 229960002130 benzoin Drugs 0.000 abstract description 3
- 235000019382 gum benzoic Nutrition 0.000 abstract description 3
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 239000012300 argon atmosphere Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000012544 monitoring process Methods 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- 238000011160 research Methods 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- FZTLLUYFWAOGGB-UHFFFAOYSA-N 1,4-dioxane dioxane Chemical compound C1COCCO1.C1COCCO1 FZTLLUYFWAOGGB-UHFFFAOYSA-N 0.000 description 1
- WHUBKNDNRSGZIS-UHFFFAOYSA-N 1-(2-fluorophenyl)-2-phenylethane-1,2-dione Chemical compound FC1=CC=CC=C1C(=O)C(=O)C1=CC=CC=C1 WHUBKNDNRSGZIS-UHFFFAOYSA-N 0.000 description 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
- 125000002672 4-bromobenzoyl group Chemical group BrC1=CC=C(C(=O)*)C=C1 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000005695 dehalogenation reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005445 isotope effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing deuterated benzoin by using deuterium as a deuterium source, which comprises the following steps of taking a benzil compound and deuterium as reaction raw materials, taking Lewis acid as a catalyst, and reacting in an organic solvent under a reducing agent to synthesize a target deuterated benzoin compound, wherein the reaction general formula is as follows:
the invention provides a preparation method of deuterated benzoin for the first time, which is simple to operate, mild in reaction conditions, environment-friendly, high in synthesis efficiency and high in deuterium doping level, wherein the yield of deuterated benzoin compounds is up to 97%, the deuterium doping rate is up to 98%, and the preparation method is suitable for large-scale production and provides a new idea and way for the development of benzoin medicaments.
Description
Technical Field
The invention belongs to the technical field of chemistry, and particularly relates to a method for preparing deuterated benzoin by using deuterium source as deuterium source.
Background
Deuterium (D or2H) Is an isotope of hydrogen (H) with twice the atomic mass of hydrogen, also known as deuterium. Deuterium, non-toxic and non-radioactive. Deuterated compounds are a very important class of high value-added chemicals. The specific binding of deuterium in molecules is often used to obtain isotopically labeled compounds, having a wide range of uses in chemical research. An increase in the strength of the C-D bond compared to C-H generally results in a significant change in reactivity. In the pharmaceutical chemistry, deuterium incorporation is a common strategy to alter the absorption, distribution, metabolism and excretion properties of candidate drugs, and deuterium labeled compounds can also serve as tracers and analytical standards to help elucidate the mechanisms and products of drug metabolism. Deuterium-labelled compounds are widely used in synthetic chemistry for kinetic isotope effect measurements and for following reaction pathways. Because of this wide range of value, there has been intense research interest in the efficient synthesis of deuterated compounds. At present, methods for preparing deuterated compounds mainly comprise methods such as hydrogen-deuterium exchange, direct deuteration and dehalogenation deuteration (J.Am.Chem.Soc.2019,141, 1467-1472; J.Am.Chem.Soc.2018,140, 10970-10974; adv.Synth.Catal.2018,360, 637-641.). Meanwhile, people also seek a synthesis method of a deuterated compound which is cheaper, green and efficient.
Benzoin, as a drug, is common in daily life. The main functions of the medicine are as follows: relieving theft, refreshing mind, promoting qi circulation, promoting blood circulation, and relieving pain. Can be used for treating apoplexy, phlegm syncope, qi stagnation, coma, heart and abdomen pain, puerperal blood faint, infantile convulsion, etc. Therefore, the research on the new synthesis method has certain academic value and application value, and especially has very important significance on the synthesis of the deuterated compound. At present, no literature reports a high-efficiency synthesis method of deuterated benzoin. Therefore, the method for synthesizing the deuterated benzoin which is mild, efficient, economic, universal and doped with high-level deuterium has very important value and application prospect.
Disclosure of Invention
The invention aims to provide a method for preparing deuterated benzoin by using deuterium as a deuterium source.
The invention aims to realize the purpose, and the method for preparing the deuterated benzoin by using the heavy water as the deuterium source is characterized in that a target deuterated benzoin compound is synthesized by using a benzil compound and the heavy water as reaction raw materials and using Lewis acid as a catalyst in an organic solvent under a reducing agent, and the reaction general formula is as follows:
the Lewis acid is AgOTf or AgBF4、CuCl、Zn(OTf)2、Cu(OTf)2、Fe(OTf)2Or Al (OTf), preferably Zn (OTf)2。
The amount of the Lewis acid is 0.01 to 100 percent, preferably 0.01 percent of the mole percent of the benzil compound.
The metal simple substance reducing agent is Fe, Cu, Zn and Mn metal simple substances, and Zn is preferred.
The amount of the reducing agent is 50 to 500 percent, preferably 300 percent of the mole percentage of the benzil compound.
The organic solvent is toluene, tetrahydrofuran, tetrahydropyran, methyl tert-butyl ether, 1,4-dioxane, dichloromethane, 1, 2-dichloroethane, N-dimethylformamide, dimethyl sulfoxide and other organic solvents, and tetrahydrofuran is preferred.
The amount of the organic solvent is 0.1mol/L to 10mol/L, preferably 1.0mol/L of the molar concentration of the benzil compound.
The reaction temperature is 25 ℃ to 140 ℃, preferably 90 ℃.
The amount of the heavy water is 100 to 500 percent, preferably 100 percent of the mole percentage of the benzil compound.
The invention has the advantages that: the invention provides a preparation method of deuterated benzoin for the first time, which is simple to operate, mild in reaction conditions, environment-friendly, high in synthesis efficiency and high in deuterium doping level, wherein the yield of deuterated benzoin compounds is up to 97%, the deuterium doping rate is up to 98%, and the preparation method is suitable for large-scale production and provides a new idea and way for the development of benzoin medicaments.
Drawings
FIG. 1 shows example 5 of deuterated compounds of the invention1H NMR spectrum.
FIG. 2 shows the preparation of deuterated compounds of example 5 of the present invention13C NMR spectrum.
FIG. 3 shows the preparation of deuterated compounds of example 6 of the present invention1H NMR spectrum.
FIG. 4 shows example 6 of deuterated compounds13C NMR spectrum.
Detailed Description
The present invention is further illustrated by the following examples and the accompanying drawings, but the present invention is not limited thereto in any way, and any modifications or alterations based on the teaching of the present invention are within the scope of the present invention.
The invention relates to a method for preparing deuterated benzoin by using deuterium as a deuterium source, which is characterized in that a target deuterated benzoin compound is synthesized by using a benzil compound and deuterium as reaction raw materials and lewis acid as a catalyst in an organic solvent under a reducing agent, and the reaction general formula is as follows:
the Lewis acid is AgOTf or AgBF4、CuCl、Zn(OTf)2、Cu(OTf)2、Fe(OTf)2Or Al (OTf)3。
The dosage of the Lewis acid is 0.01 to 100 percent of the mole percentage of the benzil compound.
The organic solvent is toluene, tetrahydrofuran, tetrahydropyran, methyl tert-butyl ether, 1,4-dioxane, dichloromethane, 1, 2-dichloroethane, N-dimethylformamide or dimethyl sulfoxide.
The dosage of the organic solvent is 0.1mol/L-10mol/L of the molar concentration of the benzil compound.
The dosage of the heavy water is 50 to 500 percent of the mole percentage of the benzil compound.
The reducing agent is a metal simple substance reducing agent.
The metal simple substance reducing agent is Fe, Cu, Zn and Mn.
The dosage of the reducing agent is 50 to 500 percent of the mole percentage of the benzil compound.
The temperature of the reaction synthesis is 25-140 ℃.
The invention is further illustrated by the following specific examples:
example 1
In a water-free and oxygen-free glove box under argon atmosphere, Zn (OTf)2(0.002mmol), Zn (0.6mmol) and benzil (0.2mmol) were added to a 10mL reaction tube in this order, followed by 2mL THF (tetrahydrofuran), and then addition of heavy water (0.2mmol) and removal from the glove box. Reaction in a 90 ℃ oil bath, TLC monitoring and I2Detecting the reaction in a color development mode, concentrating after the reaction is finished, and passing silica gel through a column to obtain the deuterated benzoin compound as a white solid, wherein the yield is 95 percent and the deuterium doping rate is 91 percent.
1H NMR(400MHz,CDCl3):7.92-7.90(m,2H),7.53-7.49(m,1H),7.41- 7.24(m,7H),5.96(d,J＝8Hz,0.09H),4.56(s,1H).
Example 2
In an anhydrous oxygen-free glove box under argon atmosphere, AgOTf (0.02mmol), Mn (1.0mmol) and 4-fluorobenzoyl (0.2mmol) were sequentially added to a 10mL reaction tube, then 2mL of 1,4-Dioxane (Dioxane) was added, and then heavy water (0.5mmol) was added and the glove box was taken out. Reaction in 110 ℃ oil bath, TLC monitoring and I2Detecting the reaction in a color development mode, concentrating after the reaction is finished, and passing silica gel through a column to obtain the deuterated benzoin compound as a white solid, wherein the yield is 97 percent, and the deuterium doping rate is 93 percent.
1H NMR(400MHz,CDCl3):8.02-7.84(m,2H),7.36-7.25(m,2H),7.13 -6.95(m,4H),5.90(d,J＝8Hz,0.07H),4.55(s,1H).
Example 3
In an anhydrous oxygen-free glove box under argon atmosphere, AgBF is put4(0.2mmol), Fe (0.1mmol) and 3-fluorobenzoyl (0.2mmol) were added to a 10mL reaction tube in this order, then 2mL tetrahydropyran was added, and then heavy water (1.0mmol) was added and taken out of the glove box. Reaction in a 70 ℃ oil bath, TLC monitoring and I2Detecting the reaction in a color development mode, concentrating after the reaction is finished, and passing silica gel through a column to obtain the deuterated benzoin compound as a white solid, wherein the yield is 95 percent, and the deuterium doping rate is 96 percent.
1H NMR(400MHz,CDCl3)7.73–7.63(m,1H),7.60(ddd,J＝9.2,2.4,1.7 Hz,1H),7.40(td,J＝8.0,5.5Hz,1H),7.35–7.21(m,2H),7.12(dd,J＝7.7,1.0Hz, 1H),7.08–6.85(m,2H),5.91(d,J＝8Hz,0.04H),4.51(s,1H).
Example 4
In a dry, oxygen-free glove box under argon atmosphere, CuCl (0.005mmol), Cu (0.5mmol) and 2-fluorobenzil (0.2mmol) were added sequentially to a 10mL reaction tube, then 2mL of 1, 2-dichloroethane were added, and then heavy water (0.1 mmo)l) out of the glove box. Reaction in 50 ℃ oil bath, TLC monitoring and I2Detecting the reaction in a color development mode, concentrating after the reaction is finished, and passing silica gel through a column to obtain the deuterated benzoin compound as a white solid, wherein the yield is 88 percent, and the deuterium doping rate is 97 percent.
1H NMR(400MHz,CDCl3)7.87(td,J＝7.6,1.8Hz,1H),7.47(dddd,J＝8.3, 7.2,5.1,1.8Hz,1H),7.29–7.15(m,3H),7.09–6.91(m,3H),(d,J＝8Hz,0.03H), 4.50(s,1H).
Example 5
In a water-free and oxygen-free glove box under argon atmosphere, Cu (OTf)2(0.01mmol), Cu (0.3mmol) and 4-methylbenzoyl (0.2mmol) were sequentially added to a 10mL reaction tube, followed by addition of 2mL of DMF (N, N-dimethylformamide) and addition of heavy water (1.0mmol) and taken out of the glove box. Reaction in 140 ℃ oil bath, TLC monitoring and I2Detecting the reaction in a color development mode, adding water for extraction after the reaction is finished, concentrating an organic phase, and passing silica gel through a column to obtain the deuterated benzoin compound as a white solid with the yield of 94 percent and the deuterium doping rate of 97 percent.
1H NMR(400MHz,CDCl3)7.74(d, J ═ 8.2Hz,2H),7.12(dd, J ═ 15.2,8.1 Hz,4H),7.03(d, J ═ 7.9Hz,2H),5.82(s,0.03H),4.49(s,1H),2.23(d, J ═ 25.9Hz, 6H)1H NMR and13the C NMR spectra are shown in FIG. 1 and FIG. 2, respectively.
Example 6
In a water-free and oxygen-free glove box under argon atmosphere, Fe (OTf)2(0.002mmol), Mn (1.0mmol) and 4-methoxybenzoyl (0.2mmol) were added to a 10mL reaction tube in this order, followed by addition of 2mL methyl t-butyl ether and addition of heavy water (0.2mmol) and removal from the glove box. Reaction in an oil bath at 80 ℃ monitored by TLC and I2Detecting the reaction process by color development, concentrating after the reaction is finished, and using siliconAnd (3) passing the gel through a column to obtain the deuterated benzoin compound as a white solid, wherein the yield is 92 percent and the deuterium doping rate is 97 percent.
1H NMR(400MHz,CDCl3)7.90(d, J ═ 8.9Hz,2H),7.25(d, J ═ 8.7Hz,2H), 6.93-6.69 (m,4H),5.85(d, J ═ 5.6Hz,0.03H),4.59(s,1H),3.77(d, J ═ 24.6Hz, 6H)1H NMR and13the C NMR spectra are shown in FIGS. 3 and 4, respectively.
Example 7
In a water-free and oxygen-free glove box under argon atmosphere, Al (OTf)3(0.002mmol), Zn (0.8mmol) and 4-chlorophenyl homoyl (0.2mmol) were sequentially added to a 10mL reaction tube, followed by addition of 2mL of toluene, addition of heavy water (0.2mmol) and removal from the glove box. Reaction in 100 ℃ oil bath, monitoring by TLC and I2And detecting the reaction process in a color development mode, concentrating after the reaction is finished, and passing silica gel through a column to obtain the deuterated benzoin compound as a white solid, wherein the yield is 88 percent and the deuterium doping rate is 94 percent.
1H NMR(400MHz,CDCl3)7.88–7.75(m,2H),7.42–7.34(m,2H),7.34– 7.19(m,4H),5.88(d,J＝2.8Hz,0.06H),4.55(d,J＝4.5Hz,1H).
Example 8
In an anhydrous oxygen-free glove box under an argon atmosphere, AgOTf (0.002mmol), Fe (1.0mmol) and 4-bromobenzoyl (0.2mmol) were sequentially added to a 10mL reaction tube, then 2mL of dichloromethane was added, and then heavy water (0.2mmol) was added and the glove box was taken out. Reaction in a 25 ℃ oil bath, monitoring by TLC and I2And detecting the reaction process in a color development mode, concentrating after the reaction is finished, and passing the concentrated solution through a silica gel column to obtain the deuterated benzoin compound as a white solid, wherein the yield is 93 percent and the deuterium doping rate is 98 percent.
1H NMR(400 MHz,CDCl3)7.78–7.69(m,2H),7.61–7.49(m,2H),7.51– 7.39(m,2H),7.23–7.08(m,2H),5.86(d,J＝5.9 Hz,0.02H),4.52(d,J＝6.0 Hz, 1H)。
Claims (10)
1. A method for preparing deuterated benzoin by using deuterium as a deuterium source is characterized in that a target deuterated benzoin compound is synthesized by using a benzil compound and deuterium as reaction raw materials and Lewis acid as a catalyst in an organic solvent under a reducing agent, and the reaction general formula is as follows:
2. the method for preparing deuterated benzoin by using heavy water as deuterium source as claimed in claim 1, wherein the Lewis acid is AgOTf or AgBF4、CuCl、Zn(OTf)2、Cu(OTf)2、Fe(OTf)2Or Al (OTf)3。
3. The method for preparing deuterated benzoin by using deuterium as a deuterium source as claimed in claim 1 or 2, wherein the lewis acid is used in an amount of 0.01-200% by mole based on the benzil compound.
4. The method of claim 1, wherein the organic solvent is toluene, tetrahydrofuran, tetrahydropyran, methyl tert-butyl ether, 1,4-dioxane, dichloromethane, 1, 2-dichloroethane, N-dimethylformamide, or dimethylsulfoxide.
5. The method for preparing deuterated benzoin by using heavy water as a deuterium source as claimed in claim 1 or 4, wherein the organic solvent is used in an amount of 0.1-10 mol/L of the molar concentration of the benzil compound.
6. The method of claim 1, wherein the deuterium oxide is used in an amount of 50-500 mol% based on the amount of the benzil compound.
7. The method for preparing deuterated benzoin by using heavy water as a deuterium source as recited in claim 1, wherein said reducing agent is an elemental metal reducing agent.
8. The method of claim 7, wherein the elemental metal reducing agent is Fe, Cu, Zn, Mn.
9. The method for preparing deuterated benzoin by using heavy water as a deuterium source as claimed in claim 1 or 7, wherein the amount of the reducing agent is 50-500% of the mole percentage of the benzil compound.
10. The method for preparing deuterated benzoin by using deuterium as a deuterium source as claimed in claim 1, wherein the reaction synthesis temperature is 25 ℃ to 140 ℃.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112939732A (en) * | 2021-02-03 | 2021-06-11 | 中国农业大学 | Synthesis method of alpha-deuterated alcohol compound and deuterated drug |
| CN114181036A (en) * | 2021-12-17 | 2022-03-15 | 安徽秀朗新材料科技有限公司 | Preparation method of deuterated bromobenzene |
| CN114213205A (en) * | 2021-12-17 | 2022-03-22 | 安徽秀朗新材料科技有限公司 | Preparation method of deuterium-substituted benzene |
| CN114181036B (en) * | 2021-12-17 | 2023-07-18 | 安徽秀朗新材料科技有限公司 | Preparation method of total deuterated bromobenzene |
| CN114213205B (en) * | 2021-12-17 | 2023-12-22 | 安徽秀朗新材料科技有限公司 | Preparation method of total deuterated benzene |
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