CN113402358A - Novel synthesis method of cyclopropyl bromide - Google Patents
Novel synthesis method of cyclopropyl bromide Download PDFInfo
- Publication number
- CN113402358A CN113402358A CN202110770182.0A CN202110770182A CN113402358A CN 113402358 A CN113402358 A CN 113402358A CN 202110770182 A CN202110770182 A CN 202110770182A CN 113402358 A CN113402358 A CN 113402358A
- Authority
- CN
- China
- Prior art keywords
- synthesis method
- cyclopropyl
- bromine
- reaction
- novel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 238000001308 synthesis method Methods 0.000 title claims description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 9
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 238000003747 Grignard reaction Methods 0.000 claims abstract description 4
- 239000012043 crude product Substances 0.000 claims abstract description 4
- 230000007062 hydrolysis Effects 0.000 claims abstract description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims abstract description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- UWTUEMKLYAGTNQ-UHFFFAOYSA-N 1,2-dibromoethene Chemical group BrC=CBr UWTUEMKLYAGTNQ-UHFFFAOYSA-N 0.000 claims description 7
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- RGDPYGJFXILIQP-UHFFFAOYSA-N 1,1-dibromocyclopropane Chemical compound BrC1(Br)CC1 RGDPYGJFXILIQP-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- RFLFDJSIZCCYIP-UHFFFAOYSA-L palladium(2+);sulfate Chemical compound [Pd+2].[O-]S([O-])(=O)=O RFLFDJSIZCCYIP-UHFFFAOYSA-L 0.000 claims 1
- GPNDARIEYHPYAY-UHFFFAOYSA-N palladium(II) nitrate Inorganic materials [Pd+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O GPNDARIEYHPYAY-UHFFFAOYSA-N 0.000 claims 1
- 229910000364 palladium(II) sulfate Inorganic materials 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 238000007256 debromination reaction Methods 0.000 abstract description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 abstract 1
- 239000006227 byproduct Substances 0.000 abstract 1
- 230000007613 environmental effect Effects 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- INLLPKCGLOXCIV-UHFFFAOYSA-N bromoethene Chemical group BrC=C INLLPKCGLOXCIV-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910000474 mercury oxide Inorganic materials 0.000 description 2
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 2
- 239000010413 mother solution Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960000740 enrofloxacin Drugs 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229960004954 sparfloxacin Drugs 0.000 description 1
- DZZWHBIBMUVIIW-DTORHVGOSA-N sparfloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DZZWHBIBMUVIIW-DTORHVGOSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/35—Preparation of halogenated hydrocarbons by reactions not affecting the number of carbon or of halogen atoms in the reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/361—Preparation of halogenated hydrocarbons by reactions involving a decrease in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/16—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic System
- C07F3/02—Magnesium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Abstract
The invention discloses a novel method for synthesizing cyclopropyl bromine, which takes ethylene dibromide as a raw material and diazomethane in Pd (oAc)2Under the action of catalyst, denitrogenation and cyclization reaction are carried out in solvent, then Grignard reaction is carried out, hydrolysis and debromination are carried out to obtain cyclopropyl bromine crude product, and then filtration, layering and normal pressure rectification are carried out to obtain pure product with the content of more than 99.5 percent, and the yield is more than 85 percent. The synthesis route has the advantages of few byproducts, mild reaction conditions, high yield, environmental friendliness and good industrial prospect.
Description
Technical Field
The invention relates to a novel method for synthesizing cyclopropyl bromide, and belongs to the technical field of synthesis of medical intermediates.
Background
The cyclopropyl bromine is mainly applied to synthesizing various drugs containing cyclopropyl such as ciprofloxacin, enrofloxacin, sparfloxacin and the like, the main synthesis method in the industry at present is to prepare the cyclopropanecarboxylic acid through decarboxylation bromination reaction with bromine in tetrachloroethane under the catalysis of mercury oxide, the method has low yield, a large amount of mercury-containing wastewater can be generated in the production process, and the environmental pollution is serious. In the prior report, bromoethylene is used as a raw material, and denitrification cyclization reaction is carried out through palladium catalysis to prepare cyclopropyl bromine.
Disclosure of Invention
Aiming at the problems, the invention provides an improved cyclopropyl bromine synthesis route, which adopts dibromoethylene as a raw material to perform denitrification and cyclization with diazomethane under the catalysis of palladium, and then prepares cyclopropyl bromine by Grignard reaction and hydrolysis debromination, and the specific mechanism and steps are as follows:
1) firstly, dibromoethylene is used as an initial raw material and reacts with diazomethane in a certain amount of solvent at a certain molar ratio and a certain reaction temperature under the action of a palladium catalyst to obtain a crude product of dibromo-cyclopropane.
2) And secondly, carrying out Grignard reaction on the crude product of the dibromo-cyclopropane and Mg, and carrying out acid washing, filtering, layering and normal-pressure distillation to obtain a cyclopropyl bromine finished product.
Further, in the above scheme, in the first step, the reaction solvent is at least one of THF, DMF, toluene, xylene, chlorobenzene, dichlorobenzene, acetonitrile, ethanol, diethyl ether, ethyl acetate;
further, in the above scheme, in the first step, the molar ratio of the vinyl bromide to the diazomethane and the palladium catalyst is 1: 1-1.5: 0.005 to 0.01;
further, in the scheme, in the first step, the reaction temperature is-15-120 ℃, and the reaction time is 5-15 h;
further, in the scheme, in the second step, the molar ratio of the trans-dibromo-cyclopropane to Mg is 1: 1.0-1.5;
further, in the scheme, in the second step, the reaction temperature is-10-80 ℃, and the reaction time is 4-20 hours;
further, in the above scheme, in the second step, the hydrolytic agent is at least one of hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and nitric acid;
further, in the scheme, in the second step, the concentration of the hydrolytic agent is 1-10%.
The invention has the beneficial effects that:
1) the method avoids the use of dangerous chemicals of vinyl bromide and mercury oxide, almost has no wastewater, is environment-friendly, has high production safety, and has very high economic and social meanings.
2) The synthesis route has the advantages of mild reaction conditions, high product yield, high purity and stable quality.
The specific implementation example is as follows:
[ example 1 ] Synthesis of cyclopropyl Bromide
Firstly, 200ml of THF/diethyl ether mixed solution (mass ratio of 1: 1) is added into a 500ml four-mouth bottle under the protection of nitrogen, the temperature is reduced to-15 ℃, and then 12.6g (0.30mol) of diazomethane and 0.67g (0.003mol) of Pd (oAc) are added2Stirring is started, 46.45g (0.25mol) of dibromoethene is slowly dropped into the mixture, the temperature is raised and the reflux is carried out after the reaction is carried out for 1.5h, the reaction is kept for 10 h-12 h, and the temperature is reduced to-5 ℃ after the TLC detection reaction is finished.
Secondly, under the protection of nitrogen, adding 120ml of THF and 6g (0.25mol) of Mg into another 500ml four-mouth bottle for Grignard initiation, then dropwise adding the reaction solution in the first step at-5-0 ℃, reacting for 1h, then heating to 40 ℃, reacting for 6h, then cooling to room temperature, slowly dropwise adding 100g of 1% diluted hydrochloric acid into the reaction mother solution, stirring for 0.5h, then standing for liquid separation, and distilling the organic phase at normal pressure to obtain 27.2g of cyclopropyl bromine; the purity is 99.8 percent, and the yield is 90 percent.
[ example 2 ] Synthesis of cyclopropyl Bromide
Firstly, adding 180ml THF into a 250ml four-mouth bottle under the protection of nitrogen, and coolingAfter a temperature of-10 ℃ was reached, 14.7g (0.35 mol) of diazomethane and 0.89g (0.004mol) of Pd (oAc)2Starting stirring, slowly dropwise adding 65.0g (0.30mol) of dibromoethylene, reacting for 1h, heating up and refluxing, keeping the temperature for reaction for 10 h-12 h, and cooling to-10 ℃ after TLC detection reaction.
Secondly, under the protection of nitrogen, adding 120ml of THF and 9.6g (0.4mol) of Mg into another 500ml four-mouth bottle, after Grignard initiation, dropwise adding the reaction solution in the first step at 0-5 ℃, reacting for 3h, then heating to 60 ℃, reacting for 6h, then cooling to room temperature, slowly dropwise adding 100g of 1% dilute sulfuric acid into the reaction mother solution, stirring for 0.5h, then standing for liquid separation, and distilling the organic phase at normal pressure to obtain 31.95g of cyclopropyl bromine; purity 99.6%, yield 88%.
[ example 3 ] Synthesis of cyclopropyl Bromide
The first step, 150ml toluene is added into a 250ml four-mouth bottle under the protection of nitrogen, the temperature is reduced to-5 ℃, and then 12.6g (0.30mol) diazomethane and 0.67g (0.003mol) Pd (oAc) are added2Starting stirring, slowly dropwise adding 46.47g (0.25mol) of liquid dibromoethene, reacting for 2h, heating up and refluxing, keeping the temperature for reacting for 4 h-6 h, and cooling to-5 ℃ after TLC detection reaction.
Secondly, under the protection of nitrogen, 100ml of THF and 6g (0.25mol) of Mg are added into another 500ml four-mouth bottle for Grignard initiation, then the reaction liquid in the first step is dripped at-5 ℃ for reaction for 2h, then the temperature is raised to 60 ℃ for reaction for 4h, then the temperature is lowered to room temperature, 100g of dilute hydrochloric acid with the concentration of 1 percent is slowly dripped into the reaction mother liquid, the mixture is stirred for 0.5h, then the mixture is kept stand for liquid separation, and the organic phase is distilled under normal pressure to obtain 25.7g of cyclopropyl bromide; the purity is 99.7 percent, and the yield is 85 percent.
Claims (9)
1. A novel cyclopropyl bromine synthesis method is characterized by comprising the following two synthesis steps:
1) dibromoethylene is used as an initial raw material, and reacts with diazomethane in a certain amount of solvent at a certain molar ratio and a certain reaction temperature under the action of a palladium catalyst to obtain dibromo-cyclopropane;
2) and (3) carrying out Grignard reaction on the crude product of the dibromo-cyclopropane and Mg, and carrying out acid washing, filtering, layering and normal pressure distillation to obtain a cyclopropyl bromine finished product.
2. The novel cyclopropyl bromide synthesis method according to claim 1, characterized in that the reaction solvent in step 1) is at least one of THF, DMF, toluene, xylene, chlorobenzene, dichlorobenzene, acetonitrile, ethanol, diethyl ether and ethyl acetate.
3. The novel cyclopropyl bromide synthesis method according to claim 1, wherein the molar ratio of the dibromoethylene to the diazomethane to the palladium catalyst in step 1) is 1: 1-2.0: 0.002 to 0.02.
4. The novel cyclopropyl bromine synthesis process according to claim 1, characterized in that step 1) said palladium catalyst is Pd (oAc)2、Pd(NO3)2、PdSO4、Pdcl2、Pd(TFA)2At least one of them.
5. The novel cyclopropyl bromide synthesis method according to claim 1, characterized in that the reaction temperature in the step 1) is-15-130 ℃, and the reaction time is 5-15 hours.
6. The novel cyclopropyl bromide synthesis method according to claim 1, characterized in that in the step 2), the molar ratio of the trans-dibromo-cyclopropane to Mg is 1: 1.0-1.5.
7. The novel cyclopropyl bromide synthesis method according to claim 1, characterized in that in the step 2), the reaction temperature is-10-80 ℃, and the reaction time is 4-20 hours.
8. The novel cyclopropyl bromine synthesis method according to claim 1, wherein the hydrolysis agent in step 2) is at least one of hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and nitric acid.
9. The novel cyclopropyl bromine synthesis method according to claim 1, wherein the concentration of the hydrolysis agent in the step 2) is 1-5%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110770182.0A CN113402358A (en) | 2021-07-08 | 2021-07-08 | Novel synthesis method of cyclopropyl bromide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110770182.0A CN113402358A (en) | 2021-07-08 | 2021-07-08 | Novel synthesis method of cyclopropyl bromide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113402358A true CN113402358A (en) | 2021-09-17 |
Family
ID=77685414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110770182.0A Pending CN113402358A (en) | 2021-07-08 | 2021-07-08 | Novel synthesis method of cyclopropyl bromide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113402358A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114315508A (en) * | 2022-01-15 | 2022-04-12 | 大连双硼医药化工有限公司 | Process for synthesizing cyclopropyl bromine |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH069499A (en) * | 1992-02-26 | 1994-01-18 | Dai Ichi Seiyaku Co Ltd | Production of halogenocyclopropanecarboxylic acid derivative |
| JPH0797353A (en) * | 1993-08-05 | 1995-04-11 | Dai Ichi Seiyaku Co Ltd | Method for selectively removing halogen |
| CN106242941A (en) * | 2016-07-08 | 2016-12-21 | 潍坊日兴化工有限公司 | A kind of synthetic method of Cyclopropylmetyl bromide |
| CN106748630A (en) * | 2016-11-28 | 2017-05-31 | 孟祥寨 | A kind of synthetic method of antalgesic intermediate Bromomethylcyclobutane |
| WO2021000248A1 (en) * | 2019-07-02 | 2021-01-07 | 凯莱英医药集团（天津）股份有限公司 | Method and apparatus for continuous synthesis of cyclopropane compounds |
-
2021
- 2021-07-08 CN CN202110770182.0A patent/CN113402358A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH069499A (en) * | 1992-02-26 | 1994-01-18 | Dai Ichi Seiyaku Co Ltd | Production of halogenocyclopropanecarboxylic acid derivative |
| JPH0797353A (en) * | 1993-08-05 | 1995-04-11 | Dai Ichi Seiyaku Co Ltd | Method for selectively removing halogen |
| CN106242941A (en) * | 2016-07-08 | 2016-12-21 | 潍坊日兴化工有限公司 | A kind of synthetic method of Cyclopropylmetyl bromide |
| CN106748630A (en) * | 2016-11-28 | 2017-05-31 | 孟祥寨 | A kind of synthetic method of antalgesic intermediate Bromomethylcyclobutane |
| WO2021000248A1 (en) * | 2019-07-02 | 2021-01-07 | 凯莱英医药集团（天津）股份有限公司 | Method and apparatus for continuous synthesis of cyclopropane compounds |
Non-Patent Citations (1)
| Title |
|---|
| I. E. DOLGS 等: ""Interaction of diazoalkanes with unsaturated compounds. 4. Cyclopropanation of vinyl and allyl halides with diazomethane in the presence of cuprous chloride complex with triphenyl phosphite"", 《N. D. ZELINSKII INSTITUTE OF ORGANIC CHEMISTRY, ACADEMY OF SCIENCES OF THE USSR, MOSCOW.》, vol. 23, no. 1, pages 135 - 138 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114315508A (en) * | 2022-01-15 | 2022-04-12 | 大连双硼医药化工有限公司 | Process for synthesizing cyclopropyl bromine |
| CN114315508B (en) * | 2022-01-15 | 2023-10-03 | 大连双硼医药化工有限公司 | Technological method for synthesizing cyclopropyl bromide |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111187153B (en) | Preparation method of 1, 3-cyclohexanedione | |
| CN109384664B (en) | Preparation method of erlotinib intermediate | |
| CN114539048B (en) | Carlong anhydride intermediate and preparation method of Carlong anhydride | |
| CN113402358A (en) | Novel synthesis method of cyclopropyl bromide | |
| CN111018757B (en) | Method for synthesizing 3-mercaptopropionic acid from acidic waste gas | |
| CN113480404A (en) | Novel method for synthesizing cyclopropyl bromide | |
| CN113773182B (en) | Method for synthesizing 6, 8-dichloro octanoate | |
| CN111099958A (en) | Novel method for synthesizing cyclopropyl bromide | |
| CN110357769B (en) | Continuous flow method for preparing 3, 5-dichloro-2-pentanone | |
| CN113443986A (en) | Preparation method of intermediate for synthesizing 3-oxo-1-cyclobutanecarboxylic acid | |
| CN112898152A (en) | Preparation method of ethoxy diethyl methylene malonate | |
| CN110713442A (en) | Preparation method of o-nitrobenzaldehyde | |
| CN113735712B (en) | Preparation method of o-nitrobenzaldehyde | |
| CN1907928A (en) | Process for preparing 2,7-dibromine fluorenes | |
| CN114292162B (en) | Preparation method of 3-chloro-beta-methylene phenethyl alcohol compound and intermediate thereof | |
| CN114249654B (en) | Process for preparing alkylanilines | |
| CN114478239A (en) | Novel synthesis method of cyclopropyl formic acid | |
| CN115322070B (en) | Preparation method of p-alkylphenyl o-fluorobenzene | |
| CA2502360C (en) | Process for producing acetylene compound | |
| CN114195626A (en) | Synthesis method of cyclopropyl formaldehyde | |
| CN110407676B (en) | Synthetic method and application of diphenylethanedione compound | |
| CN114380690A (en) | Novel preparation method of methyl cyclopropylformate | |
| CN111777544B (en) | Method for preparing N-phenylcarbazole through benzene and carbazole oxidative coupling | |
| CN117623936A (en) | Novel method for synthesizing cyclopropylamine | |
| CN107954976A (en) | A kind of method of synthesis 3,4- dimethoxy-thiophenes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |