CN117510296A - Preparation method of bromine-containing intermediate alpha, beta-dibromophenylethane - Google Patents
Preparation method of bromine-containing intermediate alpha, beta-dibromophenylethane Download PDFInfo
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- CN117510296A CN117510296A CN202311467169.3A CN202311467169A CN117510296A CN 117510296 A CN117510296 A CN 117510296A CN 202311467169 A CN202311467169 A CN 202311467169A CN 117510296 A CN117510296 A CN 117510296A
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- bromine
- dibromophenylethane
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 title claims abstract description 35
- SHKKTLSDGJRCTR-UHFFFAOYSA-N 1,2-dibromoethylbenzene Chemical compound BrCC(Br)C1=CC=CC=C1 SHKKTLSDGJRCTR-UHFFFAOYSA-N 0.000 title claims abstract description 27
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 229910052794 bromium Inorganic materials 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims abstract description 32
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000003999 initiator Substances 0.000 claims abstract description 16
- SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 claims abstract description 13
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 claims abstract description 13
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims description 17
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical group [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical group N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 14
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 claims description 10
- 238000002347 injection Methods 0.000 claims description 10
- 239000007924 injection Substances 0.000 claims description 10
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical group [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000004440 column chromatography Methods 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical class [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 239000012071 phase Substances 0.000 claims description 5
- 238000010791 quenching Methods 0.000 claims description 5
- 238000002390 rotary evaporation Methods 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 230000000171 quenching effect Effects 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 8
- 238000005893 bromination reaction Methods 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 150000003254 radicals Chemical class 0.000 abstract description 4
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 231100000572 poisoning Toxicity 0.000 abstract description 2
- 230000000607 poisoning effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 238000010586 diagram Methods 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- -1 4-substituted phenylacetylene Chemical group 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- URFPRAHGGBYNPW-UHFFFAOYSA-N 1-bromo-4-ethylbenzene Chemical compound CCC1=CC=C(Br)C=C1 URFPRAHGGBYNPW-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- JRLPEMVDPFPYPJ-UHFFFAOYSA-N 1-ethyl-4-methylbenzene Chemical compound CCC1=CC=C(C)C=C1 JRLPEMVDPFPYPJ-UHFFFAOYSA-N 0.000 description 1
- SRQOBNUBCLPPPH-UHFFFAOYSA-N 1-ethyl-4-phenylbenzene Chemical group C1=CC(CC)=CC=C1C1=CC=CC=C1 SRQOBNUBCLPPPH-UHFFFAOYSA-N 0.000 description 1
- MUJPTTGNHRHIPH-UHFFFAOYSA-N 1-tert-butyl-3-ethylbenzene Chemical compound CCC1=CC=CC(C(C)(C)C)=C1 MUJPTTGNHRHIPH-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- IIEJGTQVBJHMDL-UHFFFAOYSA-N 2-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-[2-oxo-2-[3-(sulfamoylamino)pyrrolidin-1-yl]ethyl]-1,3,4-oxadiazole Chemical compound C1CN(CC1NS(=O)(=O)N)C(=O)CC2=NN=C(O2)C3=CN=C(N=C3)NC4CC5=CC=CC=C5C4 IIEJGTQVBJHMDL-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- 239000006004 Quartz sand Substances 0.000 description 1
- 150000000475 acetylene derivatives Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000012769 display material Substances 0.000 description 1
- 238000007337 electrophilic addition reaction Methods 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- MDHYEMXUFSJLGV-UHFFFAOYSA-N phenethyl acetate Chemical compound CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000007347 radical substitution reaction Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/14—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the side-chain of aromatic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/26—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only halogen atoms as hetero-atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/23—Preparation of halogenated hydrocarbons by dehalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/287—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/297—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of bromine-containing intermediate alpha, beta-dibromophenylethane, which has the following reaction formula:in polar solution, ethylbenzene, sulfuric acid, bromide and bromate are mixed, heated and refluxed, quenched, separated, filtered, concentrated and purified. The preparation method of the bromine-containing intermediate alpha, beta-dibromophenylethane provided by the invention can obviously shorten the reaction steps, simplify the reaction conditions and reduce the production cost; the redox system consisting of bromate, bromide and sulfuric acid is used as a green bromine source, and the generated liquid bromine directly carries out free radical bromination reaction of alkyl C-H bonds under the action of an initiator, so that hidden danger of liquid bromine poisoning is avoided; the raw materials have stable purity and chemical properties, accurate dosage, controllable process, no generation of toxic and harmful substances and polysubstituted products, and environmental protection; simple and easy to operate, good in functional group tolerance, strong in substrate universality and strong in universality.
Description
Technical Field
The invention relates to the technical field of compound preparation, in particular to a preparation method of bromine-containing intermediate alpha, beta-dibromophenylethane.
Background
Phenylacetylene is an organic compound with a chemical formula of C 8 H 6 Is insoluble in water, can be mixed with most organic solvents such as ethanol, diethyl ether and the like, is an important chemical raw material and organic synthesis intermediate in the modern industry, and plays an important role in the fields of petrochemical industry, high polymer materials, pharmaceutical synthesis and the like. Aryl substituted acetylenes are also key raw materials for new photoelectric materials which have been attracting attention in recent years, such as polyphenylacetylene having conductive properties, 4-substituted phenylacetylene which is an important intermediate for liquid crystal display materials, and the like.
Alpha, beta-dibromophenylethane is an important intermediate for synthesizing phenylacetylene, and the elimination reaction of the alpha, beta-dibromophenylethane under alkaline conditions is one of main ways for industrially synthesizing phenylacetylene. At present, the alpha, beta-dibromophenylethane is mainly prepared by catalytic dehydrogenation of ethylbenzene at high temperature to obtain styrene, and then the styrene is obtained by electrophilic addition reaction with liquid bromine, wherein the reaction formula is that
The preparation process requires high-temperature catalysis at 500-700 ℃, has high requirements on production equipment and complex operation steps, also requires toxic liquid bromine, has large pollution to the environment and has strong harm to the health of staff.
Disclosure of Invention
The invention aims to provide a preparation method of bromine-containing intermediate alpha, beta-dibromophenylethane, which shortens the reaction step of producing the alpha, beta-dibromophenylethane from ethylbenzene, reduces the preparation difficulty, the production cost, the pollution to the environment and the harm to the health of staff.
In order to achieve the above purpose, the preparation method of the bromine-containing intermediate alpha, beta-dibromophenylethane provided by the invention comprises the following steps:
s1, sequentially adding ethylbenzene, DCE, sulfuric acid and bromide shown in a formula I into a three-necked flask, placing the three-necked flask into an oil bath, stirring at a certain speed, heating until reflux, and then starting to add 1/3 volume of initiator;
s2, slowly injecting the aqueous solution of bromate and the rest of the initiator solution when the system starts to reflux again, and continuing to react for 14 hours after the injection is finished;
s3, after the reaction is finished, removing the three-neck flask from the oil bath kettle to cool the reaction system, and adding a saturated sodium bisulfite solution into the reaction system to quench the reaction after the reaction system is cooled to room temperature;
s4, separating the reaction mixture after the reaction is finished, repeatedly extracting the water phase with DCM for 3 times, combining the organic phases, drying with anhydrous sodium sulfate, filtering, concentrating, and purifying the crude product by column chromatography or recrystallization to obtain the 1, 2-dibromoethylbenzene shown in the formula I;
formula I isWherein R is one of H, methyl, tertiary butyl, acetoxy, halogen and phenyl.
Preferably, the concentration of sulfuric acid is 75%; bromate is sodium bromate; the bromide is sodium bromide.
Preferably, the initiator is azobisisobutyronitrile dissolved with DCE at a concentration of 0.08moL/L, initiator: the mass ratio of ethylbenzene was 1:25.
Preferably, the ethylbenzene represented by formula I: bromate: bromide: the ratio of the amounts of sulfuric acid materials was 1:0.68:2.74:1.03.
Preferably, in the step S1, the temperature of the oil bath is set to 105 ℃, the stirring speed is 200rpm/min, and the initiator is added dropwise.
Preferably, the slow injection in the step S2 refers to that bromate is respectively injected with the initiator solution at an injection rate of 6mL/h after being dissolved in deionized water, and bromate is: the mass-to-volume ratio of deionized water was 0.308 g/1 mL.
Preferably, the amount of the saturated sodium bisulfite solution added in the step S3 is equal to the amount of DCE, the quenching reaction time is 5min, the concentration is realized by rotary evaporation under reduced pressure at 40 ℃, and petroleum ether or petroleum ether/ethyl acetate with the volume ratio of 20:1 is used as a developing agent in column chromatography.
The application of the preparation method in phenylacetylene synthesis.
Therefore, the preparation method of the bromine-containing intermediate alpha, beta-dibromophenylethane provided by the invention has the following beneficial effects:
1. compared with the traditional method, the method shortens the reaction steps, avoids the use of extremely high temperature and metal catalysts, and reduces the production cost;
2. the invention adopts a redox system composed of sodium bromate, sodium bromide and sulfuric acid as a green bromine source, and the generated liquid bromine directly carries out free radical bromination reaction of alkyl C-H bond under the action of an initiator, thereby avoiding the toxicity to staff and environment in the process of independently adding liquid bromine in the traditional method;
3. in the method provided by the invention, the three components of sodium bromate, sodium bromide and sulfuric acid generate in-situ liquid bromine through oxidation-reduction reaction, so that the generation speed of bromine can be regulated and controlled by controlling the dropping speed of sodium bromate, thereby inhibiting the electrophilic bromination reaction speed of an aromatic ring C-H bond and improving the selectivity of the bromination reaction of ethyl phenylalkyl radicals;
4. the sodium bromate and sodium bromide used in the method provided by the invention are solid substances, the purity of industrial products is stable, the dosage can be accurately calculated, and the formation of polybrominated products due to excessive bromine can be avoided; by adding the initiator, the free radical substitution reaction can be promoted, so that the formation of polysubstituted products on the aromatic ring can be avoided;
5. the sodium bromate and sodium bromide used in the method provided by the invention are both non-volatile substances, and have no toxic and harmful substances, so that the method is green and safe; the operation is simple, high temperature and high pressure are not needed, and the requirements on instruments and equipment are low; the reaction yield is good, the tolerance of the functional group is good, the universality of the substrate is strong, and the universality is strong.
The technical scheme of the invention is further described in detail through the drawings and the embodiments.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the description of the embodiments of the present invention will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a diagram of the product obtained in example 1 1 H NMR spectrum;
FIG. 2 is a diagram of the product obtained in example 1 13 C NMR spectrum;
FIG. 3 is a diagram of the product of example 2 1 H NMR spectrum;
FIG. 4 is a diagram of the product of example 2 13 C NMR spectrum;
FIG. 5 shows the product of example 3 1 H NMR spectrum;
FIG. 6 shows the product of example 3 13 C NMR spectrum;
FIG. 7 is a diagram of the product of example 4 1 H NMR spectrum;
FIG. 8 is a diagram of the product of example 4 13 C NMR spectrum;
FIG. 9 is a diagram of the product of example 5 1 H NMR spectrum；
FIG. 10 is a diagram of the product of example 5 13 C NMR spectrum;
FIG. 11 is a diagram of the product of example 6 1 HNMR spectrogram;
FIG. 12 is a diagram of the product of example 6 13 C NMR spectrum.
Detailed Description
The technical scheme of the invention is further described below through the attached drawings and the embodiments.
In order to make the objects, technical solutions and advantages of the present application more clear, thorough and complete, the technical solutions of the present invention will be clearly and completely described below through the accompanying drawings and examples. The following detailed description is of embodiments, and is intended to provide further details of the invention. Unless defined otherwise, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
Unless otherwise indicated, reagents and equipment used in the examples were all obtained commercially, with sodium bromate, sodium bromide, ethylbenzene, 1, 2-Dichloroethane (DCE) and Azobisisobutyronitrile (AIBN) purities being analytically pure; the sulfuric acid having a concentration of 75% used in the examples was obtained by dilution with concentrated sulfuric acid having a concentration of 98%.
Example 1
Preparing a bromine-containing intermediate alpha, beta-dibromophenylethane, which comprises the following steps:
s1, setting the temperature of an oil bath pot to 105 ℃, and sequentially adding 0.37mL into a 50mL three-necked flask
(3 mmoL,1 eq.) ethylbenzene, 10mL DCE, 0.27mL (3.09 mmol,1.03 eq.) in terms of weight percent
75% strength sulfuric acid, 0.85g (8.22 mmoL,2.74 eq.) of sodium bromide, and the three-necked flask was placed in an oil bath, stirring was started at a stirring speed of 200rpm/min, and after heating to reflux, 0.5mL of azobisisobutyronitrile solution (131 mg of azobisisobutyronitrile was dissolved in 10 mM DCE, and the final concentration was 0.08 mol/L) was rapidly added dropwise to the system.
S2, when the system starts to reflux again, using an automatic injection pump, 1mL of aqueous solution of sodium bromate (308 mg, 2.04mmol, 0.68 equivalent of sodium bromate dissolved in 1mL of deionized water) and 1mL of azodiisobutyronitrile solution (131 mg of azodiisobutyronitrile dissolved in 10mL of DCE, with a final concentration of 0.08 mol/L) are slowly injected at the injection rate of 6mL/h simultaneously, and the reaction is continued for 14h after the injection is completed.
S3, after the reaction is finished, the three-necked flask is moved out of the oil bath pot, 10mL of saturated sodium bisulfite solution is added into the reaction system after the reaction system is cooled to room temperature, and the quenching reaction is carried out for 5min;
s4, pouring the reaction mixture into a separating funnel after the reaction is finished, fully shaking, standing the solution for layering, using a clean conical flask to accept the oil phase below the solution after layering, simultaneously extracting the water phase again by using DCM, pouring out the oil phase, repeatedly extracting for 3 times, combining the organic phases, adding anhydrous sodium sulfate for drying, standing for 20min, and filtering to collect filtrate when the moisture in the system is fully absorbed.
S5, performing reduced pressure rotary evaporation at the temperature of 40 ℃, adding 200-mesh silica gel powder after rotary drying, performing rotary evaporation again on a small amount of DCM dissolved product to enable the product to be attached to silica gel, scraping all silica gel on the wall of a flask by a spatula, pouring the silica gel into a chromatographic column which is already installed, spreading a layer of quartz sand on the silica gel to prevent the product from being splashed when the solvent is poured, performing column chromatography operation, eluting by using petroleum ether as an expanding agent, finally collecting the target product alpha, beta-dibromophenylethane 2a, performing rotary evaporation, vacuumizing, and weighing to calculate the yield to be 65%.
The reaction is
The nmr data for product 2a were:
1 H NMR(600MHz,CDCl 3 ) Delta=7.42-7.34 (m, 5H), 5.17-5.13 (m, 1H), 4.11-4.01 (m, 2H) ppm.
13 C NMR(101MHz,CDCl 3 ) Delta = 138.7,129.3,129.0,127.8,60.0,35.2ppm spectra are shown in figure 2.
Example 2
A bromine-containing intermediate alpha, beta-dibromophenylethane was prepared in exactly the same manner as in example 1 except that ethylbenzene was p-acetoxyethylbenzene and petroleum ether/ethyl acetate (volume ratio: 20:1) was used as a developing agent for column chromatography.
The reaction formula is:
the yield was 62% and the nmr data for product 2b were:
1 H NMR(600MHz,CDCl 3 ) Delta=7.42-7.41 (m, 2H), 7.13-7.11 (m, 2H), 5.14 (dd, j=10.8, 5.4hz, 1H), 4.08-4.05 (m, 1H), 3.98 (t, j=10.2 hz, 1H), 2.31 (s, 3H) ppm.
13 C NMR(151MHz,CDCl 3 ) Delta = 169.2,151.1,136.2,129.0,122.0,50.2,35.1,21.3ppm. Spectra are shown in figure 4.
Example 3
The procedure used for the preparation of this intermediate, α, β -dibromophenylethane, was exactly the same as in example 1, except that ethylbenzene was p-bromoethylbenzene.
The reaction formula is:
yield 40%, nuclear magnetic resonance data for product 2 c:
1 H NMR(400MHz,CDCl 3 ) Delta=7.54-7.50 (m, 2H), 7.30-7.26 (m, 2H), 5.09 (dd, j=11.2, 5.2hz, 1H), 4.08-4.04 (m, 1H), 3.97 (t, j=10.8 hz, 1H) ppm.
13 C NMR(101MHz,CDCl 3 ) Delta = 137.8,132.2,129.5,123.3,49.7,34.7ppm. The spectra are shown in figure 6.
Example 4
The procedure used for the preparation of this bromine-containing intermediate 1, 2-dibromoethylbenzene was exactly the same as in example 1, except that ethylbenzene was p-methyl ethylbenzene.
The reaction formula is:
yield 65%, nuclear magnetic resonance data for product 2 e:
1 H NMR(400MHz,CDCl 3 ) δ=7.31-7.29 (m, 2H), 7.20 (d, j=7.6 hz, 2H), 5.15 (dd, j=10.4, 5.6hz, 1H), 4.10-4.00 (m, 2H), 2.37 (s, 3H) ppm.
13 C NMR(101MHz,CDCl 3 ) Delta = 139.4,135.8,129.7,127.7,51.2,35.2,21.4ppm. The spectra are shown in figure 8.
Example 5
The procedure used for the preparation of this bromine-containing intermediate, α, β -dibromophenylethane, was exactly the same as in example 1, except that ethylbenzene was 4-ethylbiphenyl.
The reaction formula is:
yield 60%, nuclear magnetic resonance data for product 2 e:
1 H NMR(400MHz,CDCl 3 ) Delta=7.62-7.59 (m, 4H), 7.49-7.44 (m, 4H), 7.37 (t, j=7.2 hz, 1H), 5.23 (dd, j=10.4, 5.6hz, 1H), 4.14-4.05 (m, 2H) ppm.
13 C NMR(101MHz,CDCl 3 ) Delta = 142.2,140.4,137.6,129.0,128.2,127.8,127.7,127.2,50.8,35.0ppm. The spectra are shown in figure 10.
Example 6
A bromine-containing intermediate 1, 2-dibromoethylbenzene was prepared in exactly the same manner as in example 1 except that ethylbenzene was 3-t-butylphenyl ethane.
The reaction formula is:
yield 67%, nuclear magnetic resonance data for product 2 f:
1 H NMR(400MHz,CDCl 3 ) Delta=7.40-7.38 (m, 2H), 7.33-7.31 (m, 1H), 7.26-7.23 (m, 1H), 5.17 (dd, j=10.0, 5.6hz, 1H), 4.11-4.01 (m, 2H), 1.351-1.345 (m, 9H) ppm.
13 C NMR(101MHz,CDCl 3 ) Delta = 151.9,138.3,128.7,126.4,125.0,124.7,51.9,35.5,34.9,31.4ppm. Spectra are shownFig. 12.
Analysis of results
As can be seen from fig. 1 to 12, examples 1 to 6 successfully prepared the compounds, and the purity of the compounds was above 95%.
Therefore, the preparation method of the bromine-containing intermediate alpha, beta-dibromophenylethane provided by the invention can obviously shorten the reaction steps, simplify the reaction conditions and reduce the production cost; the redox system consisting of bromate, bromide and sulfuric acid is used as a green bromine source, and the generated liquid bromine directly carries out free radical bromination reaction of alkyl C-H bonds under the action of an initiator, so that hidden danger of liquid bromine poisoning is avoided; the raw materials have stable purity and chemical properties, accurate dosage, controllable process, no generation of toxic and harmful substances and polysubstituted products, and environmental protection; the functional group tolerance is good, the substrate universality is strong, and the universality is strong.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention and not for limiting it, and although the present invention has been described in detail with reference to the preferred embodiments, it will be understood by those skilled in the art that: the technical scheme of the invention can be modified or replaced by the same, and the modified technical scheme cannot deviate from the spirit and scope of the technical scheme of the invention.
Claims (8)
1. The preparation method of the bromine-containing intermediate alpha, beta-dibromophenylethane is characterized by comprising the following steps:
s1, sequentially adding ethylbenzene, DCE, sulfuric acid and bromide shown in a formula I into a three-necked flask, placing the three-necked flask into an oil bath, stirring at a certain speed, heating until reflux, and then starting to add 1/3 volume of initiator;
s2, slowly injecting the aqueous solution of bromate and the rest of the initiator solution when the system starts to reflux again, and continuing to react for 14 hours after the injection is finished;
s3, after the reaction is finished, removing the three-neck flask from the oil bath kettle to cool the reaction system, and adding a saturated sodium bisulfite solution into the reaction system to quench the reaction after the reaction system is cooled to room temperature;
s4, separating the reaction mixture after the reaction is finished, repeatedly extracting the water phase with DCM for 3 times, combining the organic phases, drying with anhydrous sodium sulfate, filtering, concentrating, and purifying the crude product by column chromatography or recrystallization to obtain the 1, 2-dibromoethylbenzene shown in the formula I;
formula I isWherein R is one of H, methyl, tertiary butyl, acetoxy, halogen and phenyl.
2. The method for preparing bromine-containing intermediate alpha, beta-dibromophenylethane according to claim 1, which is characterized in that: the concentration of sulfuric acid is 75%; bromate is sodium bromate; the bromide is sodium bromide.
3. The method for preparing bromine-containing intermediate alpha, beta-dibromophenylethane according to claim 1, which is characterized in that: the initiator is azobisisobutyronitrile dissolved by DCE and the concentration is 0.08mol/L, and the initiator is: the mass ratio of ethylbenzene was 1:25.
4. The method for preparing bromine-containing intermediate alpha, beta-dibromophenylethane according to claim 1, which is characterized in that: ethylbenzene represented by formula I: bromate: bromide: the ratio of the amounts of sulfuric acid materials was 1:0.68:2.74:1.03.
5. The method for preparing bromine-containing intermediate alpha, beta-dibromophenylethane according to claim 1, which is characterized in that: in the step S1, the temperature of the oil bath pot is set to 105 ℃, the stirring speed is 200rpm/min, and the initiator is dropwise added.
6. The method for preparing bromine-containing intermediate alpha, beta-dibromophenylethane according to claim 1, which is characterized in that: the slow injection in the step S2 refers to the injection of bromate and initiator solution at the injection rate of 6mL/h after the bromate is dissolved in deionized water, respectively: the mass-to-volume ratio of deionized water was 0.308 g/1 mL.
7. The method for preparing bromine-containing intermediate alpha, beta-dibromophenylethane according to claim 1, which is characterized in that: the amount of the saturated sodium bisulfite solution added in the step S3 is equal to the amount of DCE, the quenching reaction time is 5min, the concentration is realized by rotary evaporation under reduced pressure at 40 ℃, and petroleum ether or petroleum ether/ethyl acetate with the volume ratio of 20:1 is used as a developing agent in column chromatography.
8. Use of the preparation method according to any one of claims 1-7 in phenylacetylene synthesis.
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