CN115611768B - Synthesis method of 3, 4-dichlorobenzonitrile - Google Patents
Synthesis method of 3, 4-dichlorobenzonitrile Download PDFInfo
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- CN115611768B CN115611768B CN202211419975.9A CN202211419975A CN115611768B CN 115611768 B CN115611768 B CN 115611768B CN 202211419975 A CN202211419975 A CN 202211419975A CN 115611768 B CN115611768 B CN 115611768B
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- dichlorobenzonitrile
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- KUWBYWUSERRVQP-UHFFFAOYSA-N 3,4-dichlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1Cl KUWBYWUSERRVQP-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 238000001308 synthesis method Methods 0.000 title abstract description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000010949 copper Substances 0.000 claims abstract description 30
- 239000012074 organic phase Substances 0.000 claims abstract description 26
- 239000002904 solvent Substances 0.000 claims abstract description 21
- 239000003446 ligand Substances 0.000 claims abstract description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims abstract description 18
- CFPZDVAZISWERM-UHFFFAOYSA-N 4-bromo-1,2-dichlorobenzene Chemical compound ClC1=CC=C(Br)C=C1Cl CFPZDVAZISWERM-UHFFFAOYSA-N 0.000 claims abstract description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 229910052802 copper Inorganic materials 0.000 claims abstract description 10
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 9
- 238000001914 filtration Methods 0.000 claims abstract description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims abstract description 9
- 235000019341 magnesium sulphate Nutrition 0.000 claims abstract description 9
- 238000001816 cooling Methods 0.000 claims abstract description 8
- 238000010438 heat treatment Methods 0.000 claims abstract description 8
- 238000010791 quenching Methods 0.000 claims abstract description 8
- 230000000171 quenching effect Effects 0.000 claims abstract description 8
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 3
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 17
- 238000004440 column chromatography Methods 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- 239000003480 eluent Substances 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical group CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 6
- ZKXWKVVCCTZOLD-FDGPNNRMSA-N copper;(z)-4-hydroxypent-3-en-2-one Chemical compound [Cu].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O ZKXWKVVCCTZOLD-FDGPNNRMSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003208 petroleum Chemical group 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 20
- 239000000460 chlorine Substances 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- WYUIWKFIFOJVKW-UHFFFAOYSA-N 1,2-dichloro-4-methylbenzene Chemical compound CC1=CC=C(Cl)C(Cl)=C1 WYUIWKFIFOJVKW-UHFFFAOYSA-N 0.000 description 4
- -1 3, 4-dichloro-trichlorobenzyl Chemical group 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- FPENCTDAQQQKNY-UHFFFAOYSA-N 3,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(F)=C1 FPENCTDAQQQKNY-UHFFFAOYSA-N 0.000 description 1
- BTBFCBQZFMQBNT-UHFFFAOYSA-N 3,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1F BTBFCBQZFMQBNT-UHFFFAOYSA-N 0.000 description 1
- GJNGXPDXRVXSEH-UHFFFAOYSA-N 4-chlorobenzonitrile Chemical compound ClC1=CC=C(C#N)C=C1 GJNGXPDXRVXSEH-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical group [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of organic chemical synthesis, and discloses a synthesis method of 3, 4-dichlorobenzonitrile. Adding 3, 4-dichloro bromobenzene, a reducing agent, a solvent, a copper catalyst and a ligand into a reactor, and then injecting CO 2 And NH 3 Heating to 60-150 ℃, stirring and reacting 2-7 h, cooling to room temperature after the reaction is finished, quenching the reaction by using saturated sodium bicarbonate water solution, extracting an organic phase in the system by using ethyl acetate, and then sequentially drying magnesium sulfate, filtering by using diatomite, concentrating and purifying to obtain the 3, 4-dichlorobenzonitrile. The invention synthesizes CO which is easy to obtain 2 And NH 3 The method is a cyanide source, and 3, 4-dichlorobenzonitrile is obtained by one-step synthesis, and has the advantages of few reaction steps, green environmental protection and the like.
Description
Technical Field
The invention belongs to the field of organic chemical synthesis, and particularly relates to a synthesis method of 3, 4-dichlorobenzonitrile.
Background
The 3, 4-dichlorobenzonitrile is an organic intermediate with wide application, and is widely applied to industries such as medicines, materials, pesticides and the like. Meanwhile, 3, 4-dichlorobenzonitrile is used as a key intermediate, and can be used for preparing fluorine-containing organic compounds such as 3, 4-difluorobenzonitrile, 3, 4-difluorobenzoic acid and the like. At present, research on a synthetic method of 3, 4-dichlorobenzonitrile is also receiving more and more attention.
The synthesis method of the 3, 4-dichlorobenzonitrile mainly comprises the following steps:
(1) In the patent CN105732427B, the synthetic route is as follows, the p-chlorobenzonitrile reacts with chlorine to synthesize 3, 4-dichlorobenzonitrile, and the method has low product purity, raw materials are not easy to obtain and the toxicity of a reaction reagent is high;
；
(2) In the patent CN110317150A, the synthetic route is divided into two types, namely (i) the synthetic route is as follows, 3, 4-dichloro-trichlorobenzyl is prepared by synthesis starting from 3, 4-dichloro-toluene, and then the 3, 4-dichlorobenzonitrile is obtained by reaction with ammonium chloride at high temperature;
；
(ii) The synthetic route is as follows, 3, 4-dichlorobenzonitrile is prepared by 3, 4-dichlorotoluene through an ammoxidation method;
；
(3) In the patent CN102924329A, 3, 4-dichlorobenzonitrile is synthesized by taking a mixed carrier of alumina and titanium oxide as a catalyst under a relatively mild condition;
(4) In patent CN1137779C, the preparation of 3, 4-dichlorobenzonitrile by ammoxidation using a multicomponent catalyst with vanadium and phosphine as main catalysts is reported.
In summary, the reported methods have mainly the following disadvantages: complicated steps, long reaction time, high cost, serious pollution, higher temperature, use of extremely toxic reagents, more reaction byproducts, difficult separation and the like.
Disclosure of Invention
Aiming at the technical problems existing in the prior art, the invention aims to provide a synthesis method of 3, 4-dichlorobenzonitrile, which has the advantages of few reaction steps, easily available raw materials, high product purity and suitability for mass production.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a synthetic method of 3, 4-dichlorobenzonitrile comprises the following synthetic route:
；
the synthesis steps are as follows: adding 3, 4-dichloro bromobenzene, a reducing agent, a solvent, a copper catalyst and a ligand into a reactor, and then injecting CO 2 And NH 3 Heating to 60-150deg.C, stirring for 2-7-h, cooling to room temperature, quenching with saturated sodium bicarbonate aqueous solution, extracting organic phase with ethyl acetate, drying with magnesium sulfate, filtering with diatomite, concentrating,Purifying to obtain 3, 4-dichlorobenzonitrile;
wherein the mol ratio of 3, 4-dichloro bromobenzene, reducing agent, copper catalyst and solvent is 1:3-5:0.05-0.2:5-50, the mol ratio of copper catalyst and ligand is 1:1-4, CO 2 And NH 3 Pressure ratio of 1:1, CO 2 Is 1-10 atm;
the reducing agent is Cl 3 SiH、Ph 3 SiH、CH 3 SiH or Et 3 SiH；
The solvent is N-methylpyrrolidone, 2-methyltetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide or hexamethylphosphoramide;
the copper catalyst is CuCl, cuCl 2 、CuBr、CuBr 2 、CuI、CuI 2 、Cu(C 2 O 4 )、Cu(OAc) 2 、CuOTf、Cu(OTf) 2 、Cu(acac) 2 、Cu(PPh 3 ) 3 Cl、CuSO 4 、Cu(CH 3 CN) 4 PF 6 Or Cu (Py) 4 (OTf) 2 ；
The ligand is one of L1-L12; the structural formulas of L1-L12 are respectively as follows:
。
preferably, the purification treatment is column chromatography separation, the eluent adopted is a mixed solution of a solvent A and a solvent B according to the volume ratio of 1:1-20, the solvent A is dichloromethane, ethyl acetate or chloroform, and the solvent B is n-pentane, n-hexane, petroleum ether or methanol.
The beneficial effects are that: the invention synthesizes CO which is easy to obtain 2 And NH 3 The method is a cyanide source, and 3, 4-dichlorobenzonitrile is obtained by one-step synthesis, and has the advantages of few reaction steps, green environmental protection and the like.
Detailed Description
The present invention will be described in detail with reference to examples, but the scope of the present invention is not limited to the examples.
The ligand structural formulas involved in the following examples are as follows:
。
example 1
A synthesis method of 3, 4-dichlorobenzonitrile comprises the following steps: adding 3, 4-dichloro bromobenzene and Cl into a reactor 3 SiH、Cu(acac) 2 Ligand L1,NAfter injection of methyl pyrrolidone and magneton into CO 2 And NH 3 Heating the system to 150 ℃, cooling to room temperature after reacting 4 h, quenching the reaction by using saturated sodium bicarbonate aqueous solution, extracting organic phases in the system by using ethyl acetate, merging the organic phases, drying the organic phases by using magnesium sulfate for 30 min, filtering by using diatomite, concentrating the organic phases, separating a crude product by column chromatography, wherein a chromatographic column for the column chromatography is a silica gel column, an eluent is a mixed solution obtained by mixing dichloromethane and n-hexane according to the volume ratio of 1:10, decompressing and distilling the obtained component containing the target product to remove the solvent, thus obtaining the target product 3, 4-dichlorobenzonitrile, and the yield is 55%; wherein, 3, 4-dichloro bromobenzene:Cl 3 SiH、Cu(acac) 2 、NThe molar ratio of methylpyrrolidone is 1:3:0.05:5, cu (acac) 2 The molar ratio of the ligand L1 to CO is 1:1 2 And NH 3 Pressure ratio of 1:1, CO 2 Is 1 atm.
And (3) carrying out nuclear magnetic characterization on a target product, wherein the result is as follows:
1 H NMR (400 MHz, DMSO d6 ): δ 7.55(d, 1H), 7.44 (d, 1H), 7.39 (m, 1H)。
melting point: 74-75 ℃.
Density: 1.40 g/cm 3 。
Example 2
A synthesis method of 3, 4-dichlorobenzonitrile comprises the following steps: adding 3, 4-dichloro bromobenzene and Ph into a reactor 3 SiH、Cu(PPh 3 ) 3 After Cl, ligand L2, 2-methyltetrahydrofuran and magneton, CO is injected 2 And NH 3 The reaction mixture was cooled to room temperature after reaction 6 h, quenched with saturated aqueous sodium bicarbonate, and quenched with ethyl acetateExtracting organic phases in a system, combining the organic phases, drying the organic phases with magnesium sulfate for 30 min, filtering the diatomite, concentrating the organic phases, separating a crude product by column chromatography, wherein a chromatographic column for the column chromatography is a silica gel column, an eluent is a mixed solution obtained by mixing ethyl acetate and petroleum ether according to a volume ratio of 1:8, and the obtained component containing a target product is subjected to reduced pressure distillation to remove a solvent, so that the target product 3, 4-dichlorobenzonitrile is obtained, and the yield is 78%; wherein, 3, 4-dichloro bromobenzene:Ph 3 SiH、Cu(PPh 3 ) 3 The molar ratio of Cl to 2-methyltetrahydrofuran is 1:4:0.07:15, cu (PPh) 3 ) 3 The molar ratio of Cl to ligand L2 is 1:1.4, CO 2 And NH 3 Pressure ratio of 1:1, CO 2 Is 1 atm.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Example 3
A synthesis method of 3, 4-dichlorobenzonitrile comprises the following steps: adding 3, 4-dichloro bromobenzene and CH into a reactor 3 SiH、Cu(CH 3 CN) 4 PF 6 After ligand L7, 1, 4-dioxane and magneton, CO is injected 2 And NH 3 Heating the system to 100 ℃, cooling to room temperature after reacting 7 and h, quenching the reaction by using saturated sodium bicarbonate aqueous solution, extracting organic phases in the system by using ethyl acetate, merging the organic phases, drying the organic phases by using magnesium sulfate for 30 min, filtering by using diatomite, concentrating the organic phases, separating a crude product by column chromatography, wherein a chromatographic column for the column chromatography is a silica gel column, an eluent is a mixed solution obtained by mixing dichloromethane and methanol according to the volume ratio of 1:1, decompressing and distilling the obtained component containing the target product to remove the solvent, thus obtaining the target product 3, 4-dichlorobenzonitrile, and the yield is 83%; wherein, 3, 4-dichloro bromobenzene:CH 3 SiH、Cu(CH 3 CN) 4 PF 6 The molar ratio of the 1, 4-dioxane is 1:5:0.1:25, cu (CH) 3 CN) 4 PF 6 The molar ratio of ligand L7 is 1:1.5, CO 2 And NH 3 Pressure ratio of 1:1, CO 2 Is 2 atm.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Example 4
A synthesis method of 3, 4-dichlorobenzonitrile comprises the following steps: adding 3, 4-dichloro bromobenzene and Et into a reactor 3 SiH、Cu(Py) 4 (OTf) 2 Ligand L8,N,NAfter dimethylformamide and magnetons, CO injection 2 And NH 3 Heating the system to 150 ℃, cooling to room temperature after reacting 3 h, quenching the reaction by using saturated sodium bicarbonate aqueous solution, extracting organic phases in the system by using ethyl acetate, merging the organic phases, drying the organic phases by using magnesium sulfate for 30 min, filtering by using diatomite, concentrating the organic phases, separating a crude product by column chromatography, wherein a chromatographic column for the column chromatography is a silica gel column, an eluent is a mixed solution obtained by mixing ethyl acetate and n-pentane according to the volume ratio of 1:6, decompressing and distilling the obtained component containing the target product to remove a solvent, thus obtaining the target product 3, 4-dichlorobenzonitrile, and the yield is 96%; wherein, 3, 4-dichloro bromobenzene:Et 3 SiH、Cu(Py) 4 (OTf) 2 、N,NThe molar ratio of dimethylformamide is 1:3:0.2:35, cu (Py) 4 (OTf) 2 The molar ratio of the ligand L8 to CO is 1:1.5 2 And NH 3 Pressure ratio of 1:1, CO 2 Is 4 atm.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Example 5
A synthesis method of 3, 4-dichlorobenzonitrile comprises the following steps: adding 3, 4-dichloro bromobenzene and Cl into a reactor 3 SiH、Cu(OTf) 2 After ligand L9, hexamethylphosphoramide and magneton, CO is injected 2 And NH 3 Heating the system to 150 ℃, cooling to room temperature after reacting 2 h, quenching the reaction with saturated sodium bicarbonate aqueous solution, extracting organic phases in the system with ethyl acetate, merging the organic phases, drying for 30 min with magnesium sulfate, filtering with diatomite, concentrating the organic phases, separating a crude product by column chromatography, wherein the column chromatography is a silica gel column, the eluent is a mixed solution obtained by mixing diethyl ether and n-hexane according to the volume ratio of 1:5, and decompressing and distilling the obtained component containing the target product to remove the solvent to obtain the target product 3, 4-dichlorobenzonitrile, wherein the yield is 90%; wherein, 3, 4-dichloro bromobenzene:Cl 3 SiH、Cu(OTf) 2 The molar ratio of hexamethylphosphoramide is 1:4:0.1:40, cu (OTf) 2 The molar ratio of ligand L9 is 1:3, CO 2 And NH 3 Pressure ratio of 1:1, CO 2 Is 5 atm.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Example 6
A synthesis method of 3, 4-dichlorobenzonitrile comprises the following steps: adding 3, 4-dichloro bromobenzene and Ph into a reactor 3 SiH、Cu(OAc) 2 After ligand L11, dimethyl sulfoxide and magneton, CO is injected 2 And NH 3 Heating the system to 130 ℃, cooling to room temperature after reacting 6 h, quenching the reaction by using saturated sodium bicarbonate aqueous solution, extracting organic phases in the system by using ethyl acetate, merging the organic phases, drying the organic phases by using magnesium sulfate for 30 min, filtering by using diatomite, concentrating the organic phases, separating a crude product by column chromatography, wherein a chromatographic column for column chromatography is a silica gel column, an eluent is a mixed solution obtained by mixing ethyl acetate and methylene dichloride according to the volume ratio of 1:15, decompressing and distilling the obtained component containing the target product to remove a solvent, thus obtaining the target product 3, 4-dichlorobenzonitrile, and the yield is 91%; wherein, 3, 4-dichloro bromobenzene:Ph 3 SiH、Cu(OAc) 2 The molar ratio of dimethyl sulfoxide is 1:5:0.08:50, cu (OAc) 2 The molar ratio of the ligand L11 to CO is 1:2 2 And NH 3 Pressure ratio of 1:1, CO 2 Is 6 atm.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Claims (2)
1. A method for synthesizing 3, 4-dichlorobenzonitrile is characterized in that: adding 3, 4-dichloro bromobenzene, a reducing agent, a copper catalyst, a ligand and a solvent into a reactor, and then injecting CO 2 And NH 3 Heating to 60-150 ℃, stirring and reacting 2-7 h, cooling to room temperature after the reaction is finished, quenching and reacting by using saturated sodium bicarbonate water solution, extracting an organic phase in a system by using ethyl acetate, and then sequentially drying magnesium sulfate, filtering by using diatomite, concentrating and purifying to obtain 3, 4-dichlorobenzonitrile;
wherein the mol ratio of 3, 4-dichloro bromobenzene, reducing agent, copper catalyst and solvent is 1:3-5:0.05-0.2:5-50, the mol ratio of copper catalyst and ligand is 1:1-4, CO 2 And NH 3 Pressure ratio of 1:1, CO 2 Is 1-10 atm; the reducing agent is Cl 3 SiH、Ph 3 SiH、CH 3 SiH or Et 3 SiH; the solvent is N-methylpyrrolidone, 2-methyltetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide or hexamethylphosphoramide;
the copper catalyst is Cu (OAc) 2 、Cu(OTf) 2 、Cu(acac) 2 、Cu(PPh 3 ) 3 Cl、Cu(CH 3 CN) 4 PF 6 Or Cu (Py) 4 (OTf) 2 ；
The ligand is one of L1, L2, L7, L8, L9 or L11 in L1-L12; the structural formulas of L1-L12 are respectively as follows:
。
2. the method for synthesizing 3, 4-dichlorobenzonitrile according to claim 1, wherein: the purification treatment is column chromatography separation, the adopted eluent is a mixed solution of a solvent A and a solvent B according to the volume ratio of 1:1-20, the solvent A is dichloromethane, ethyl acetate or diethyl ether, and the solvent B is n-pentane, n-hexane, dichloromethane, petroleum ether or methanol.
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| CN202211419975.9A CN115611768B (en) | 2022-11-14 | 2022-11-14 | Synthesis method of 3, 4-dichlorobenzonitrile |
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| CN202211419975.9A CN115611768B (en) | 2022-11-14 | 2022-11-14 | Synthesis method of 3, 4-dichlorobenzonitrile |
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Citations (5)
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| JPH03145449A (en) * | 1989-10-27 | 1991-06-20 | Ihara Chem Ind Co Ltd | Production of 3,4-difluorobenzonitrile |
| JPH0672980A (en) * | 1992-08-26 | 1994-03-15 | Asahi Glass Co Ltd | Production of 3,4-difluorobenzonitrile |
| CN107001278A (en) * | 2014-10-08 | 2017-08-01 | Ucb生物制药私人有限公司 | Tetrahydro isoquinoline derivative |
| CN108017557A (en) * | 2017-12-06 | 2018-05-11 | 中国科学院兰州化学物理研究所苏州研究院 | A kind of Process for the cyanation for preparing nitrile compounds |
| CN113896652A (en) * | 2021-10-08 | 2022-01-07 | 江苏超跃化学有限公司 | Preparation method of 3, 4-dichlorobenzonitrile |
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| JPH03145449A (en) * | 1989-10-27 | 1991-06-20 | Ihara Chem Ind Co Ltd | Production of 3,4-difluorobenzonitrile |
| JPH0672980A (en) * | 1992-08-26 | 1994-03-15 | Asahi Glass Co Ltd | Production of 3,4-difluorobenzonitrile |
| CN107001278A (en) * | 2014-10-08 | 2017-08-01 | Ucb生物制药私人有限公司 | Tetrahydro isoquinoline derivative |
| CN108017557A (en) * | 2017-12-06 | 2018-05-11 | 中国科学院兰州化学物理研究所苏州研究院 | A kind of Process for the cyanation for preparing nitrile compounds |
| CN113896652A (en) * | 2021-10-08 | 2022-01-07 | 江苏超跃化学有限公司 | Preparation method of 3, 4-dichlorobenzonitrile |
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| Zeng, Yuehua etal.Copper-catalyzed enantioselective radical 1,4-difunctionalization of 1,3-enynes.《Journal of the American Chemical Society》.2020,18014-18021. * |
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