CN112281182A - Method for preparing deuterated aromatic hydrocarbon under electrochemical condition - Google Patents
Method for preparing deuterated aromatic hydrocarbon under electrochemical condition Download PDFInfo
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- 150000004945 aromatic hydrocarbons Chemical class 0.000 title claims abstract description 79
- 238000000034 method Methods 0.000 title claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- -1 tetrabutylammonium tetrafluoroborate Chemical compound 0.000 claims abstract description 25
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000003792 electrolyte Substances 0.000 claims abstract description 22
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 13
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 6
- ODHXBMXNKOYIBV-UHFFFAOYSA-N triphenylamine Chemical compound C1=CC=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 ODHXBMXNKOYIBV-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000003487 electrochemical reaction Methods 0.000 claims abstract description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 72
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 25
- 238000001035 drying Methods 0.000 claims description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000012074 organic phase Substances 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 12
- 239000000741 silica gel Substances 0.000 claims description 12
- 229910002027 silica gel Inorganic materials 0.000 claims description 12
- 238000002386 leaching Methods 0.000 claims description 11
- 238000000926 separation method Methods 0.000 claims description 3
- 125000006617 triphenylamine group Chemical group 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000005070 sampling Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 abstract description 10
- 229910052805 deuterium Inorganic materials 0.000 abstract description 8
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 abstract description 7
- 125000003118 aryl group Chemical group 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 3
- 150000001503 aryl iodides Chemical class 0.000 abstract description 2
- 239000003638 chemical reducing agent Substances 0.000 abstract description 2
- 230000007935 neutral effect Effects 0.000 abstract description 2
- 239000007800 oxidant agent Substances 0.000 abstract description 2
- 230000001590 oxidative effect Effects 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 150000001499 aryl bromides Chemical class 0.000 abstract 1
- 150000001500 aryl chlorides Chemical class 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 239000007788 liquid Substances 0.000 description 10
- 238000011068 loading method Methods 0.000 description 10
- 238000005868 electrolysis reaction Methods 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 239000003814 drug Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 150000001491 aromatic compounds Chemical class 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- APSMUYYLXZULMS-UHFFFAOYSA-N 2-bromonaphthalene Chemical compound C1=CC=CC2=CC(Br)=CC=C21 APSMUYYLXZULMS-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- WYURNTSHIVDZCO-SVYQBANQSA-N oxolane-d8 Chemical compound [2H]C1([2H])OC([2H])([2H])C([2H])([2H])C1([2H])[2H] WYURNTSHIVDZCO-SVYQBANQSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- MKJIEFSOBYUXJB-VFJJUKLQSA-N (3r,11br)-3-(2-methylpropyl)-9,10-bis(trideuteriomethoxy)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one Chemical compound C1CN2C[C@@H](CC(C)C)C(=O)C[C@@H]2C2=C1C=C(OC([2H])([2H])[2H])C(OC([2H])([2H])[2H])=C2 MKJIEFSOBYUXJB-VFJJUKLQSA-N 0.000 description 1
- SXNCMLQAQIGJDO-UHFFFAOYSA-N 2-bromo-5-(5-bromothiophen-2-yl)thiophene Chemical compound S1C(Br)=CC=C1C1=CC=C(Br)S1 SXNCMLQAQIGJDO-UHFFFAOYSA-N 0.000 description 1
- JDDAFHUEOVUDFJ-UHFFFAOYSA-N 2-iodobenzonitrile Chemical compound IC1=CC=CC=C1C#N JDDAFHUEOVUDFJ-UHFFFAOYSA-N 0.000 description 1
- PJUAIXDOXUXBDR-UHFFFAOYSA-N 3-iodo-9-phenylcarbazole Chemical compound C12=CC=CC=C2C2=CC(I)=CC=C2N1C1=CC=CC=C1 PJUAIXDOXUXBDR-UHFFFAOYSA-N 0.000 description 1
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 1
- TVQLYTUWUQMGMP-UHFFFAOYSA-N 5-iodo-1h-indole Chemical compound IC1=CC=C2NC=CC2=C1 TVQLYTUWUQMGMP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- RSQXKVWKJVUZDG-UHFFFAOYSA-N 9-bromophenanthrene Chemical compound C1=CC=C2C(Br)=CC3=CC=CC=C3C2=C1 RSQXKVWKJVUZDG-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UHYPYGJEEGLRJD-UHFFFAOYSA-N cadmium(2+);selenium(2-) Chemical compound [Se-2].[Cd+2] UHYPYGJEEGLRJD-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000005695 dehalogenation reaction Methods 0.000 description 1
- 150000001975 deuterium Chemical group 0.000 description 1
- 229950005031 deutetrabenazine Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- XZIAFENWXIQIKR-UHFFFAOYSA-N ethyl 4-bromobenzoate Chemical compound CCOC(=O)C1=CC=C(Br)C=C1 XZIAFENWXIQIKR-UHFFFAOYSA-N 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000005445 isotope effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- WPGAGRPPDYAZAD-UHFFFAOYSA-N methyl 4-bromo-2-methoxybenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1OC WPGAGRPPDYAZAD-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for preparing deuterated aromatic hydrocarbon under electrochemical conditions, which comprises the following steps: 1) preparing an electrolyte: adding halogenated aromatic hydrocarbon, sacrificial reagent, tetrabutylammonium tetrafluoroborate and D to a solvent2O, uniformly mixing to obtain electrolyte; 2) and respectively inserting a platinum electrode or a carbon rod as an anode and a lead electrode as a cathode into the electrolyte, introducing direct current into the electrolyte under the stirring condition to perform electrochemical reaction, and separating to obtain the deuterated aromatic hydrocarbon after the reaction is finished. The invention takes heavy water as a deuterium source, triphenylamine and triphenylphosphine as sacrificial reagents, reaction substrates can be aryl bromide, aryl chloride or aryl iodide, the reaction is carried out in a neutral environment at room temperature, strong chemical oxidant and strong chemical reducing agent are not involved, the reaction condition is mild, the yield is high, and the deuteration rate of the prepared deuterated aryl is high.
Description
Technical Field
The invention belongs to the technical field of electrolytic production of organic compounds, and particularly relates to a method for preparing deuterated aromatic hydrocarbon under electrochemical conditions.
Background
Deuterium is an inexpensive nonradioactive hydrogen isotope. Furthermore, cleavage of the C-D bond is more difficult than cleavage of the C-H bond. Due to the above characteristics, deuterated compounds are widely applied in many fields, such as kinetic isotope effects, quantitative analysis, drug research, and the like. In 2017, the united states Food and Drug Administration (FDA) approved austedo (deuttebrabenazine) as the first deuterated drug (c.schmidt, nat. biotechnol.,2017, 35, 493-. The deuterated drugs improve the pharmacokinetic properties and toxicity of the non-deuterated drugs and have wide application prospects.
Almost all commercial drugs contain aromatic ring structures. Thus, deuteration of aromatic compounds has been the focus of attention of organic chemists. Although the direct Hydrogen Isotope Exchange (HIE) method is more attractive, it has poor selectivity and functional group tolerance, limiting the range of applications. Halogenated aromatic hydrocarbons, as a bulk chemical feedstock, remain a common choice for the synthesis of deuterated aromatic compounds. Traditional metal halogen exchange, free radical induction, transition metal catalysis and the like all need harsh conditions, such as metal halogen use dangerous alkyl lithium reagent, need lower reaction temperature (-78 ℃), and functional group tolerance is not good (H.J.Reich, J.org.chem.2012,77, 5471-5491) faces the problem of convenient operation; radical induction uses a virulent tin reagent, and requires a large amount of expensive deuterated tetrahydrofuran as a solvent (m. tomonobu, tetrahedron.2011,67, 1158-; transition metal catalysis often requires reaction under basic conditions with noble metals as catalysts, and the deuteration reagents used are expensive and special (c.s. donald, Tetrahedron lett, 2014,55, 3305-3307), which face green and economic problems. Recently, photocatalytic dehalogenation deuteration reaction (y. dong, ACS nano.2019,13, 10754-10760; c. liu, nat. commun.2018, 9,80) with heavy water as deuterium source was reported. However, the synthesis of heavy metal-containing Au/CdS or CdSe materials is required, and the use of a solvent amount of heavy water as a deuterium source poses problems of greenness and economy. It is necessary to research a more convenient, safe, green and economical method for preparing deuterated aromatics.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a simple, convenient, economical and safe method for preparing deuterated aromatic hydrocarbon aiming at the defects in the prior art.
In order to solve the technical problems, the technical scheme provided by the invention is as follows:
a method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
1) preparing an electrolyte: adding halogenated aromatic compounds to the solventHydrocarbons, sacrificial agents, tetrabutylammonium tetrafluoroborate and D2O, uniformly mixing to obtain electrolyte;
2) and respectively inserting a platinum electrode or a carbon rod as an anode and a lead electrode as a cathode into the electrolyte, introducing direct current into the electrolyte under the stirring condition to perform electrochemical reaction, and separating to obtain the deuterated aromatic hydrocarbon after the reaction is finished.
According to the scheme, the solvent in the step 1) is N, N-Dimethylformamide (DMF).
According to the scheme, the halogenated aromatic hydrocarbon in the step 1) is brominated aromatic hydrocarbon, chlorinated aromatic hydrocarbon or iodo aromatic hydrocarbon.
According to the scheme, when the halogenated aromatic hydrocarbon in the step 1) is brominated aromatic hydrocarbon or chlorinated aromatic hydrocarbon, the sacrificial reagent is triphenylamine (NPh)3) The molar ratio of triphenylamine to brominated aromatic hydrocarbon or chlorinated aromatic hydrocarbon is 3-5: 5;
when the halogenated aromatic hydrocarbon is iodo aromatic hydrocarbon, the sacrificial reagent is triphenylphosphine (PPh)3) The molar ratio of triphenylphosphine to iodoarene is 1-2: 1.
according to the scheme, the molar ratio of tetrabutylammonium tetrafluoroborate to halogenated aromatic hydrocarbon in the step 1) is 1: 1 to 2.
According to the scheme, step 1) is D2The molar ratio of O to halogenated aromatic hydrocarbon is 4-40: 1.
according to the scheme, the direct current in the step 2) is 5-20 mA, and the electrochemical reaction time is 2-9 h.
According to the scheme, the separation method in the step 2) comprises the following steps: and after the reaction is finished, extracting the reaction solution by using ethyl acetate, spin-drying the organic phase, carrying out dry-method sampling by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain the deuterated aromatic hydrocarbon.
Halogenated aromatic hydrocarbon can be reduced to generate active intermediates of halogen anions and aryl under the electrochemical condition, the halogen anions are oxidized into free radicals at the anode, the free radicals substitute hydrogen on triphenylamine to generate halogenated triphenylamine, and the aryl free radicals can react with heavy water in a system to generate deuterated compounds. Iodine removed from aryl iodide cannot replace hydrogen on the triphenylamine aryl ring, and triphenylphosphine serving as a sacrificial reagent is oxidized into triphenylphosphine oxide at an electrochemical anode, so that the reduction reaction of a cathode can be promoted.
The invention has the beneficial effects that:
the invention takes the deuterium source as the deuterium source, has high deuterium atom utilization rate, cheap, safe and green deuterium source, cheap and easily obtained sacrificial reagents of triphenylamine and triphenylphosphine and good compatibility of reaction substrates, can be halogenated polycyclic aromatic hydrocarbon or alkyl aromatic hydrocarbon, functional groups such as halogen atom, ether bond, cyano-group, ester group, trialkyl silicon group and the like, and substituted aromatic compounds such as thiophene, indole and carbazole and the like, the reaction is carried out in neutral environment at room temperature, strong chemical oxidant and strong chemical reducing agent are not involved, the reaction condition is mild, the reaction process is simple and easy to operate, the reaction can be better realized by using a dry battery as a power supply (see example 33), the method is flexible and strong in practicability, the prepared deuterated aromatic hydrocarbon has high deuteration rate and high purity, the preparation and separation operations are simple and convenient, and the cost is low, wherein various deuterated aromatic compounds are important raw materials for organic synthesis.
Detailed Description
In order to make the technical solutions of the present invention better understood by those skilled in the art, the present invention is further described in detail with reference to the following examples.
Examples 1 to 21
The method is characterized in that brominated aromatic hydrocarbon or chlorinated aromatic hydrocarbon is used as a raw material to prepare deuterated aromatic hydrocarbon, the used sacrificial reagent is triphenylamine, and the molecular formulas, the yield and the deuteration rate of the halogenated aromatic hydrocarbon and the generated deuterated aromatic hydrocarbon used in examples 1-21 are shown in Table 1.
TABLE 1
The specific preparation method is exemplified as follows, and the preparation method of the other examples is similar to that of the following:
example 1
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask (15mL) equipped with magnetons was added 0.5mmol of 2-bromonaphthalene(103.5mg) and 0.3mmol NPh3(73.6mg), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box, and 5.0mmol of D was added to the system2O (90. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 15mA for electrolysis reaction for 3 hours at room temperature, extracting the reaction solution by using ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-method sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon with the yield of 99% and the deuteration rate of 95%.
The nuclear magnetic data of the deuterated aromatic hydrocarbon obtained in the example are as follows:1H NMR(400MHz,CDCl3)δ7.85-7.83(m, 4H),7.48-7.46(m,3H).13C NMR(101MHz,CDCl3)δ133.38,127.85,127.73,125.78, 125.69.
example 3
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask equipped with magnetons (15mL) were added 0.5mmol of 9-bromophenanthrene (128.6mg) and 0.3mmol of NPh3(73.6mg), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box, and 5.0mmol of D was added to the system2O (90. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 15mA for electrolysis reaction for 3 hours at room temperature, extracting the reaction solution by using ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-method sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon, wherein the yield is more than 99% and the deuteration rate is 95%.
The nuclear magnetic data of the deuterated aromatic hydrocarbon obtained in the example are as follows:1H NMR(400MHz,CDCl3)δ8.70(d,J＝ 8.0Hz,2H),7.90(d,J＝8.4Hz,2H),7.75(s,1H),7.68-7.59(m,4H).13C NMR(101 MHz,CDCl3)δ131.98,131.92,130.24,128.54,128.49,126.89,126.76,126.54, 122.62.
example 13
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask equipped with magnetons (15mL) were added 0.5mmol of 4-bromobenzonitrile (91.0mg) and 0.3mmol of NPh3(73.6mg), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box, and 5.0mmol of D was added to the system2O (90. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 10mA for electrolysis reaction for 4.5 hours at room temperature, extracting the reaction solution by ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-method sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon with the yield of 80% and the deuteration rate of 90%.
The nuclear magnetic data of the deuterated aromatic hydrocarbon obtained in the example are as follows:1H NMR(400MHz,CDCl3)δ7.67(d,J＝ 8.4Hz,4H),7.48(d,J＝7.6Hz,4H).13C NMR(101MHz,CDCl3)δ132.19,129.04, 118.93,112.41.
example 16
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask equipped with magnetons (15mL) were added 0.5mmol of ethyl 4-bromobenzoate (114.5mg) and 0.3mmol of NPh3(73.6mg), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box, and 5.0mmol of D was added to the system2O (90. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 10mA for electrolysis reaction for 4.5 hours at room temperature, extracting the reaction solution by ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-method sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon with the yield of 69% and the deuteration rate of 90%.
Example 17
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask equipped with magnetons (15mL) were added 0.5mmol of methyl 2-methoxy-4-bromobenzoate (122.5mg) and 0.3mmol of NPh3(73.6mg), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box, and 5.0mmol of D was added to the system2O (90. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 20mA for electrolysis reaction for 2.5 hours at room temperature, extracting the reaction solution by ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-method sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon with the yield of 91% and the deuteration rate of 93%.
The nuclear magnetic data of the deuterated aromatic hydrocarbon obtained in the example are as follows:1H NMR(400MHz,CDCl3)δ7.80(d,J＝7.6Hz,1H),6.99-6.97(m,2H),3.91(s,3H),3.89(s,3H).13C NMR(101MHz,CDCl3) δ166.68,159.03,133.52,131.63,119.94,111.77,55.91,52.02.
example 18
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask (15mL) equipped with magnetons were added 0.25mmol of 5,5 '-dibromo-2, 2' -bithiophene (81.0mg) and 0.3mmol of NPh3(73.6mg), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box, and 5.0mmol of D was added to the system2O (90. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 20mA for electrolysis reaction for 2.5 hours at room temperature, extracting the reaction solution by ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-method sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon with the yield of 72% and the deuteration rate of 92%.
Examples 22 to 32
The method is characterized in that iodo aromatic hydrocarbon is used as a raw material to prepare deuterated aromatic hydrocarbon, and the sacrificial reagent is triphenylphosphine. The molecular formula, yield and deuteration rate of the used halogenated aromatic hydrocarbon and the generated deuteration aromatic hydrocarbon are shown in table 2.
TABLE 2
The specific preparation method is exemplified as follows, and the preparation method of the other examples is similar to that of the following:
example 29
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask (15mL) equipped with magnetons were added 0.5mmol of 2-iodobenzonitrile (114.5mg) and 1.0mmol of PPh3(262.3mg, 1.0mmol), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box and 10.0mmol of D was added to the system2O (180. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 15mA for electrolysis reaction for 4 hours at room temperature, extracting the reaction solution by using ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-process sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon, wherein the yield is more than 99%, and the deuteration rate is more than 99%.
The nuclear magnetic data of the deuterated aromatic hydrocarbon obtained in the example are as follows:1H NMR(400MHz,CDCl3)δ7.68-7.66 (m,1H),7.64-7.60(m,1H),7.51-7.47(m,2H).13C NMR(101MHz,CDCl3)δ132.76, 132.12,129.09,128.97,118.84,112.27.
example 31
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask (15mL) equipped with magnetons were added 0.5mmol of 5-iodoindole (121.5mg) and 1.0mmol of PPh3(262.3mg), then 0.25m electrolyte was added to the glove boxmol of tetrabutylammonium tetrafluoroborate (82.3mg), 10.0mmol of D was added to the system2O (180. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 15mA for electrolysis reaction for 4 hours at room temperature, extracting the reaction solution by using ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-method sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon, wherein the yield is 84%, and the deuteration rate is more than 87%.
Example 32
A method for preparing deuterated aromatic hydrocarbon under electrochemical conditions comprises the following steps:
to a dry three-necked flask (15mL) equipped with magnetons were added 0.3mmol of 3-iodo-9-phenylcarbazole (110.8mg) and 1.0mmol of PPh3(262.3mg), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box, and 10.0mmol of D was added to the system2O (180. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, platinum electrode and lead electrode (1.5X 0.03 cm)3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the direct current of 15mA for electrolysis reaction for 4 hours at room temperature, extracting the reaction solution by using ethyl acetate after the reaction is finished, spin-drying the organic phase, carrying out dry-method sample loading by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain deuterated aromatic hydrocarbon with the yield of 89% and the deuteration rate of 92%.
The nuclear magnetic data of the deuterated aromatic hydrocarbon obtained in the example are as follows:1H NMR(400MHz,CDCl3)δ8.16-8.14 (m,2H),7.62-7.55(m,4H),7.48-7.38(m,5H),7.30-7.27(m,1H).13C NMR(101MHz, CDCl3)δ140.80,137.61,129.82,127.39,127.08,125.87,125.76,123.26,120.26, 120.15,119.83,109.71.
example 33
The deuterated aromatic hydrocarbon was prepared by the method of example 1, except that a dry cell was used as a power source, comprising the following steps:
to a magneton-equipped glass tube (15mL) were added 0.5mmol of 2-bromonaphthalene (103.5mg) and 0.3mmol of NPh3(73.6mg), then 0.25mmol of tetrabutylammonium tetrafluoroborate (82.3mg) as electrolyte was added to the glove box, and 5.0mmol of D was added to the system2O (90. mu.L) and 6.0mL of ultra-dry N, N-dimethylformamide, a carbon rod and a lead foil (1.5X 0.03 cm) fixed with a copper wire3) Respectively inserting the solution below the liquid level as an anode and a cathode, stirring the reaction system under the condition that a dry battery (1.5V multiplied by 3) is used as a power supply to perform electrolytic reaction for 3.5h (current is 8-10mA) at room temperature, extracting the reaction solution by using ethyl acetate after the reaction is finished, spin-drying the organic phase, performing dry sample loading by using 200-300-mesh silica gel, performing gradient elution by using petroleum ether and ethyl acetate, wherein the yield is 77% and the deuteration rate is 90%.
The nuclear magnetic data of the deuterated aromatic hydrocarbon obtained in the example are as follows:1H NMR(400MHz,CDCl3)δ7.85-7.83 (m,4H),7.48-7.46(m,3H).13C NMR(101MHz,CDCl3)δ133.38,127.85,127.73, 125.78,125.69。
Claims (8)
1. a method for preparing deuterated aromatic hydrocarbon under electrochemical conditions is characterized by comprising the following steps:
1) preparing an electrolyte: adding halogenated aromatic hydrocarbon, sacrificial reagent, tetrabutylammonium tetrafluoroborate and D to a solvent2O, uniformly mixing to obtain electrolyte;
2) and respectively inserting a platinum electrode or a carbon rod as an anode and a lead electrode as a cathode into the electrolyte, introducing direct current into the electrolyte under the stirring condition to perform electrochemical reaction, and separating to obtain the deuterated aromatic hydrocarbon after the reaction is finished.
2. The method for preparing deuterated aromatic hydrocarbon under electrochemical conditions as recited in claim 1, wherein the solvent in step 1) is N, N-dimethylformamide.
3. The method for preparing deuterated aromatic hydrocarbon under the electrochemical condition as recited in claim 1, wherein the halogenated aromatic hydrocarbon in step 1) is a brominated aromatic hydrocarbon, a chlorinated aromatic hydrocarbon or an iodo aromatic hydrocarbon.
4. The method for preparing deuterated aromatic hydrocarbon under the electrochemical condition as recited in claim 1, wherein in the step 1) when the halogenated aromatic hydrocarbon is brominated aromatic hydrocarbon or chlorinated aromatic hydrocarbon, the sacrificial reagent is triphenylamine, and the molar ratio of triphenylamine to brominated aromatic hydrocarbon or chlorinated aromatic hydrocarbon is 3-5: 5;
when the halogenated aromatic hydrocarbon is iodo aromatic hydrocarbon, the sacrificial reagent is triphenylphosphine, and the molar ratio of the triphenylphosphine to the iodo aromatic hydrocarbon is (1-2): 1.
5. the method for preparing deuterated aromatic hydrocarbons under electrochemical conditions according to claim 1, wherein the molar ratio of tetrabutylammonium tetrafluoroborate to halogenated aromatic hydrocarbons in step 1) is 1: 1 to 2.
6. The method for preparing deuterated aromatic hydrocarbon under electrochemical conditions as recited in claim 1, wherein step 1) said step D is performed2The molar ratio of O to halogenated aromatic hydrocarbon is 4-40: 1.
7. the method of claim 1, wherein the magnitude of the direct current in the step 2) is 5 to 20mA, and the electrochemical reaction time is 2 to 9 hours.
8. The method for preparing deuterated aromatic hydrocarbon under electrochemical conditions as recited in claim 1, wherein the separation method in step 2) comprises: and after the reaction is finished, extracting the reaction solution by using ethyl acetate, spin-drying the organic phase, carrying out dry-method sampling by using 200-300-mesh silica gel, carrying out gradient leaching by using petroleum ether and ethyl acetate, and separating to obtain the deuterated aromatic hydrocarbon.
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