CN111635300B - Method for preparing deuterated benzoin by taking heavy water as deuterium source - Google Patents
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- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 title claims abstract description 44
- 229910052805 deuterium Inorganic materials 0.000 title claims abstract description 30
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 title claims abstract description 29
- 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 20
- 238000000034 method Methods 0.000 title claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- -1 benzil compound Chemical class 0.000 claims abstract description 29
- 238000010348 incorporation Methods 0.000 claims description 11
- 238000011161 development Methods 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 9
- 239000012300 argon atmosphere Substances 0.000 claims description 9
- 238000012544 monitoring process Methods 0.000 claims description 9
- 239000000741 silica gel Substances 0.000 claims description 9
- 229910002027 silica gel Inorganic materials 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- 238000001514 detection method Methods 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 abstract description 9
- 239000003960 organic solvent Substances 0.000 abstract description 8
- 239000002841 Lewis acid Substances 0.000 abstract description 7
- 150000007517 lewis acids Chemical class 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 238000002360 preparation method Methods 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
- 239000003054 catalyst Substances 0.000 abstract description 3
- 235000019382 gum benzoic Nutrition 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000013459 approach Methods 0.000 abstract description 2
- 238000009509 drug development Methods 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 239000013076 target substance Substances 0.000 abstract 1
- 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
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- 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 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 206010042772 syncope Diseases 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- REKFALFAMJBFCR-UHFFFAOYSA-N 1-(4-bromophenyl)-2-phenylethane-1,2-dione Chemical compound C1=CC(Br)=CC=C1C(=O)C(=O)C1=CC=CC=C1 REKFALFAMJBFCR-UHFFFAOYSA-N 0.000 description 1
- NTINAJCDYRYMML-UHFFFAOYSA-N 1-(4-methoxyphenyl)-2-phenylethane-1,2-dione Chemical compound C1=CC(OC)=CC=C1C(=O)C(=O)C1=CC=CC=C1 NTINAJCDYRYMML-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- 238000007193 benzoin condensation reaction Methods 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
- 230000036461 convulsion Effects 0.000 description 1
- 238000005695 dehalogenation reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000005445 isotope effect Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process 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
- 230000037361 pathway Effects 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 230000001737 promoting effect Effects 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
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
Landscapes
- 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 taking heavy water as a deuterium source, which is characterized in that a benzil compound and heavy water are taken as reaction raw materials, lewis acid is taken as a catalyst, and the deuterated benzoin compound as a target substance is obtained by reaction and synthesis in an organic solvent under the condition of a reducing agent, wherein the reaction general formula is as follows: The invention provides a preparation method of deuterated benzoin for the first time, which has the advantages of simple operation, mild reaction condition, environment protection, high synthesis efficiency and high 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 thought and approach for benzoin drug development.
Description
Technical Field
The invention belongs to the technical field of chemistry, and particularly relates to a method for preparing deuterated benzoin by taking heavy water as a deuterium source.
Background
Deuterium (D or 2 H) is an isotope of hydrogen (H), and the atomic mass is twice that of hydrogen, also known as deuterium. Deuterium, non-toxic and non-radioactive. Deuterated compounds are a very important class of high value-added chemicals. Specific binding of deuterium in molecules is often used to obtain isotopically labeled compounds, and has wide-ranging 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 terms of pharmaceutical chemistry, deuterium incorporation is a common strategy to alter absorption, distribution, metabolism and excretion characteristics of candidate drugs, deuterium labeled compounds can also serve as tracers and analytical criteria, helping elucidate the mechanism and products of drug metabolism. Deuterium labeled compounds are widely used in synthetic chemistry to measure and track the reaction pathway by kinetic isotope effects. Because of this broad value, there is a great deal of research interest in the efficient synthesis of deuterated compounds. At present, the preparation methods of deuterated compounds mainly comprise hydrogen-deuterium exchange, direct deuteration, dehalogenation deuteration and other methods (J.Am.Chem.Soc.2019,141,1467-1472;J.Am.Chem.Soc.2018,140, 10970-10974;Adv.Synth.Catal.2018,360,637-641.)., and meanwhile, a cheaper, green and efficient synthetic method of the deuterated compounds is also sought.
Benzoin is a drug that is common in everyday life. The main functions of the medicine are as follows: the medicine has the functions of promoting qi and blood circulation, and relieving pain. Can be used for treating apoplexy, phlegm syncope, qi stagnation syncope, middle-jiao malignant coma, heart and abdomen pain, puerperal blood dizziness, infantile convulsion, etc. Therefore, the research on the new synthesis method has certain academic value and application value, and particularly has very important significance on the synthesis of deuterated compounds. At present, no literature reports about a high-efficiency synthetic method of deuterated benzoin. Therefore, the development of a mild, efficient, economic and universal deuterated benzoin synthesis method with high-level deuterium incorporation has very important value and application prospect.
Disclosure of Invention
The invention aims to provide a method for preparing deuterated benzoin by taking heavy water as a deuterium source.
The invention aims to realize the method for preparing deuterated benzoin by taking heavy water as a deuterium source, which is to take benzil compound and heavy water as reaction raw materials, take Lewis acid as a catalyst, and react and synthesize the target deuterated benzoin compound in an organic solvent under the condition of a reducing agent, wherein the reaction general formula is as follows:
The lewis acid is AgOTf, agBF 4、CuCl、Zn(OTf)2、Cu(OTf)2、Fe(OTf)2 or Al (OTf), preferably Zn (OTf) 2.
The Lewis acid is used in an amount of 0.01% to 100%, preferably 0.01% by mole of the benzil compound.
The metal simple substance reducer is Fe, cu, zn, mn metal simple substance, preferably Zn.
The reducing agent is used in an amount of 50-500%, preferably 300% by mole 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, preferably tetrahydrofuran.
The organic solvent is used in an amount of 0.1mol/L to 10mol/L, preferably 1.0mol/L, based on the molar concentration of the benzil compound.
The reaction temperature is 25℃to 140℃and preferably 90 ℃.
The heavy water is used in an amount of 100% -500%, preferably 100% of the benzil compound in mole percent.
The invention has the advantages that: the invention provides a preparation method of deuterated benzoin for the first time, which has the advantages of simple operation, mild reaction condition, environment protection, high synthesis efficiency and high 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 thought and approach for benzoin drug development.
Drawings
FIG. 1 is a 1 H NMR spectrum of deuterated compound according to example 5 of the present invention.
FIG. 2 is a 13 C NMR spectrum of deuterated compound of example 5 according to the invention.
FIG. 3 is a 1 H NMR spectrum of deuterated compound according to example 6 of the present invention.
FIG. 4 is a 13 C NMR spectrum of a deuterated compound of example 6 according to the invention.
Detailed Description
The invention is further described below with reference to examples and figures, but is not limited in any way, and any alterations or substitutions based on the teachings of the invention are within the scope of the invention.
The method for preparing deuterated benzoin by taking heavy water as deuterium source is characterized in that a benzil compound and heavy water are taken as reaction raw materials, lewis acid is taken as a catalyst, and the reaction is carried out in an organic solvent under the condition of a reducing agent to obtain the target deuterated benzoin compound, wherein the reaction general formula is as follows:
the Lewis acid is AgOTf, agBF 4、CuCl、Zn(OTf)2、Cu(OTf)2、Fe(OTf)2 or Al (OTf) 3.
The dosage of the Lewis acid is 0.01-100% of the mole percentage of the benzil compound.
The organic solvent is toluene, tetrahydrofuran, tetrahydropyran, methyl tertiary 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 benzil compound.
The dosage of the heavy water is 50-500% of the mole percentage of the benzil compound.
The reducing agent is a metal simple substance reducing agent.
The metal simple substance reducer is Fe, cu, zn, mn.
The usage amount of the reducing agent is 50-500% of the mole percentage of the benzil compound.
The reaction synthesis temperature is 25-140 ℃.
The invention is further illustrated by the following examples:
example 1
Zn (OTf) 2 (0.002 mmol), zn (0.6 mmol) and benzil (0.2 mmol) were sequentially added to a 10mL reaction tube in an anhydrous anaerobic glove box under an argon atmosphere, followed by addition of 2mL THF (tetrahydrofuran) and then addition of heavy water (0.2 mmol) to exit the glove box. The reaction is carried out in an oil bath at 90 ℃, TLC monitoring and I 2 color development mode detection are carried out, after the reaction is completed, concentration is carried out, the deuterated benzoin compound is obtained by passing through a silica gel column, the white solid is obtained, the yield is 95%, and the deuterium incorporation rate is 91%.
1H NMR(400MHz,CDCl3):δ7.92-7.90(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
AgOTf (0.02 mmol), mn (1.0 mmol) and 4-fluorobenzoyl (0.2 mmol) were sequentially added to a 10mL reaction tube in an anhydrous anaerobic glove box under an argon atmosphere, followed by 2mL of 1,4-Dioxane, and then heavy water (0.5 mmol) was added to the glove box. The reaction is carried out in an oil bath at 110 ℃, TLC monitoring and I 2 color development mode detection are carried out, after the reaction is completed, concentration is carried out, the deuterated benzoin compound is obtained by passing through a silica gel column, the white solid is obtained, the yield is 97%, and the deuterium incorporation rate is 93%.
1H NMR(400MHz,CDCl3):δ8.02-7.84(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
AgBF 4 (0.2 mmol), fe (0.1 mmol) and 3-fluorobenzoyl (0.2 mmol) were sequentially added to a 10mL reaction tube in an anhydrous anaerobic glove box under an argon atmosphere, followed by addition of 2mL tetrahydropyran and then addition of heavy water (1.0 mmol) to discharge the glove box. The reaction is carried out in an oil bath at 70 ℃, TLC monitoring and I 2 color development mode detection are carried out, after the reaction is completed, concentration is carried out, the deuterated benzoin compound is obtained by passing through a silica gel column, the white solid is obtained, the yield is 95%, and the deuterium incorporation rate is 96%.
1H NMR(400MHz,CDCl3)δ7.73–7.63(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 an anhydrous anaerobic glove box under argon atmosphere, cuCl (0.005 mmol), cu (0.5 mmol) and 2-fluorobenzoyl (0.2 mmol) were sequentially added to a10 mL reaction tube, followed by 2mL of 1, 2-dichloroethane, and then heavy water (0.1 mmol) was added to discharge the glove box. The reaction is carried out in an oil bath at 50 ℃, TLC monitoring and I 2 color development mode detection are carried out, after the reaction is completed, concentration is carried out, the deuterated benzoin compound is obtained by passing through a silica gel column, the white solid is obtained, the yield is 88%, and the deuterium incorporation rate is 97%.
1H NMR(400MHz,CDCl3)δ7.87(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
Cu (OTf) 2 (0.01 mmol), cu (0.3 mmol) and 4-methylbenzoyl (0.2 mmol) were sequentially added to a 10mL reaction tube in an anhydrous anaerobic glove box under an argon atmosphere, then 2mL DMF (N, N-dimethylformamide) was added, and then heavy water (1.0 mmol) was added to discharge the glove box. The reaction is carried out in an oil bath at 140 ℃, TLC monitoring and I 2 color development mode detection are carried out, after the reaction is completed, water is added for extraction, an organic phase is concentrated, a silica gel is used for passing through a column to obtain the deuterated benzoin compound, the white solid is obtained, the yield is 94%, and the deuterium incorporation rate is 97%.
1H NMR(400MHz,CDCl3)δ7.74(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). Specific 1 H NMR and 13 C NMR spectra are shown in FIGS. 1 and 2, respectively.
Example 6
Fe (OTf) 2 (0.002 mmol), mn (1.0 mmol) and 4-methoxybenzil (0.2 mmol) were sequentially added to a 10mL reaction tube in an anhydrous anaerobic glove box under an argon atmosphere, followed by addition of 2mL of methyl t-butyl ether and then addition of heavy water (0.2 mmol) to exit the glove box. The reaction is carried out in an oil bath at 80 ℃, the reaction progress is detected by TLC monitoring and I 2 color development, after the reaction is completed, concentration is carried out, the deuterated benzoin compound is obtained by passing silica gel through a column, the white solid is obtained, the yield is 92%, and the deuterium incorporation rate is 97%.
1H NMR(400MHz,CDCl3)δ7.90(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). Specific 1 H NMR and 13 C NMR spectra are shown in FIGS. 3 and 4, respectively.
Example 7
Al (OTf) 3 (0.002 mmol), zn (0.8 mmol) and 4-chlorobenzoyl (0.2 mmol) were sequentially added to a 10mL reaction tube in an anhydrous anaerobic glove box under an argon atmosphere, followed by addition of 2mL toluene and then addition of heavy water (0.2 mmol) to discharge the glove box. The reaction is carried out in an oil bath at 100 ℃, the reaction progress is detected by TLC monitoring and I 2 color development, after the reaction is completed, concentration is carried out, the deuterated benzoin compound is obtained by passing silica gel through a column, the white solid is obtained, the yield is 88%, and the deuterium incorporation rate is 94%.
1H NMR(400MHz,CDCl3)δ7.88–7.75(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
AgOTf (0.002 mmol), fe (1.0 mmol) and 4-bromobenzil (0.2 mmol) were sequentially added to a 10mL reaction tube in an anhydrous anaerobic glove box under argon atmosphere, followed by addition of 2mL of methylene chloride and then addition of heavy water (0.2 mmol) to exit the glove box. The reaction is carried out in an oil bath at 25 ℃, the reaction progress is detected by TLC monitoring and I 2 color development, after the reaction is completed, concentration is carried out, the deuterated benzoin compound is obtained by passing silica gel through a column, the white solid is obtained, the yield is 93%, and the deuterium incorporation rate is 98%.
1H NMR(400 MHz,CDCl3)δ7.78–7.69(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 (1)
1. A method for preparing deuterated benzoin by taking heavy water as deuterium source is characterized in that 0.002mmol of Zn (OTf) 2, 0.6mmol of Zn and 0.2mmol of benzil are sequentially added into a 10mL reaction tube in an anhydrous anaerobic glove box under the argon atmosphere, 2mL of tetrahydrofuran is added, 0.2mmol of heavy water is added and is sent out of the glove box, the reaction is carried out in an oil bath at 90 ℃, TLC monitoring and I 2 color development mode detection are carried out, after the reaction is completed, concentration is carried out, silica gel is used for passing through a column to obtain deuterated benzoin compound, white solid is obtained, the yield is 95%, and the deuterium incorporation rate is 91%.
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CN110128233A (en) * | 2019-05-21 | 2019-08-16 | 南京工业大学 | A kind of preparation method of deuterated alcohols or aminated compounds |
CN111004076A (en) * | 2019-12-16 | 2020-04-14 | 云南民族大学 | Method for preparing deuterated amino acid ester by using deuterium source as deuterium source |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110128233A (en) * | 2019-05-21 | 2019-08-16 | 南京工业大学 | A kind of preparation method of deuterated alcohols or aminated compounds |
CN111004076A (en) * | 2019-12-16 | 2020-04-14 | 云南民族大学 | Method for preparing deuterated amino acid ester by using deuterium source as deuterium source |
Non-Patent Citations (3)
Title |
---|
Asymmetric synthesis of benzoin by samarium diiodide-mediated enantioselective protonation;Takeuchi, Seji;Bulletin of the Chemical Society of Japan;第65卷(第7期);2001-2003 * |
Practical Method for Reductive Deuteration of Ketones with Magnesium and D2O;Zhu, Nengbo;Organic Letters;第22卷(第3期);991-996 * |
Visible-Light-Mediated Umpolung Reactivity of Imines: Ketimine Reductions with Cy 2 NMe and Water;Rui Wang等;organic letters;20181231;第20卷;2433-2436 * |
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