CN112939755A - Novel process for preparing 5-chloro-2, 3-dihydro-1-indanone - Google Patents
Novel process for preparing 5-chloro-2, 3-dihydro-1-indanone Download PDFInfo
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- CN112939755A CN112939755A CN202110110422.4A CN202110110422A CN112939755A CN 112939755 A CN112939755 A CN 112939755A CN 202110110422 A CN202110110422 A CN 202110110422A CN 112939755 A CN112939755 A CN 112939755A
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- chloride
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- indanone
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- 238000004519 manufacturing process Methods 0.000 title claims description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims abstract description 54
- 238000006243 chemical reaction Methods 0.000 claims abstract description 50
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 47
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 38
- 239000003054 catalyst Substances 0.000 claims abstract description 33
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 claims abstract description 32
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 239000011780 sodium chloride Substances 0.000 claims abstract description 19
- 239000011592 zinc chloride Substances 0.000 claims abstract description 19
- 239000002994 raw material Substances 0.000 claims abstract description 16
- 235000005074 zinc chloride Nutrition 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 238000005580 one pot reaction Methods 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 238000004321 preservation Methods 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- 238000012544 monitoring process Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- -1 4-chlorphenyl Chemical group 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000005457 ice water Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 230000005311 nuclear magnetism Effects 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 14
- 238000007086 side reaction Methods 0.000 abstract description 7
- 239000007788 liquid Substances 0.000 abstract description 5
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 239000000575 pesticide Substances 0.000 abstract description 3
- 239000000654 additive Substances 0.000 description 11
- 230000000996 additive effect Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- 239000012264 purified product Substances 0.000 description 9
- FKGDMSJKLIQBQS-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(Cl)C(Cl)=C1 FKGDMSJKLIQBQS-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- AYFJBHFMQODYBC-UHFFFAOYSA-N 3-chloro-1-(4-chlorophenyl)propan-1-one Chemical compound ClCCC(=O)C1=CC=C(Cl)C=C1 AYFJBHFMQODYBC-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 3
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- FFKGOJWPSXRALK-SNAWJCMRSA-N (e)-3-(3-chlorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(Cl)=C1 FFKGOJWPSXRALK-SNAWJCMRSA-N 0.000 description 2
- AJUAASWQUWIMHM-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)propan-2-one Chemical compound CC(=O)CC1=CC=C(Cl)C(Cl)=C1 AJUAASWQUWIMHM-UHFFFAOYSA-N 0.000 description 2
- QEYMMOKECZBKAC-UHFFFAOYSA-N 3-chloropropanoic acid Chemical compound OC(=O)CCCl QEYMMOKECZBKAC-UHFFFAOYSA-N 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 2
- 229910021577 Iron(II) chloride Inorganic materials 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000011403 purification operation Methods 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000007039 two-step reaction Methods 0.000 description 2
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 1
- ZKUOUPNEARANHV-UHFFFAOYSA-N 2,3,5-trichloro-2,3-dihydroinden-1-one Chemical compound ClC=1C=C2C(C(C(C2=CC=1)=O)Cl)Cl ZKUOUPNEARANHV-UHFFFAOYSA-N 0.000 description 1
- YRUBJDXEYFCYCX-UHFFFAOYSA-N 2-(3-chlorophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=CC(Cl)=C1 YRUBJDXEYFCYCX-UHFFFAOYSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- CYABLYFBMFFNPD-UHFFFAOYSA-N 3-(3-chlorophenyl)propanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC(Cl)=C1 CYABLYFBMFFNPD-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000010813 internal standard method Methods 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/08—Halides
- B01J27/10—Chlorides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/125—Halogens; Compounds thereof with scandium, yttrium, aluminium, gallium, indium or thallium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/138—Halogens; Compounds thereof with alkaline earth metals, magnesium, beryllium, zinc, cadmium or mercury
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/20—Catalysts, in general, characterised by their form or physical properties characterised by their non-solid state
- B01J35/27—Catalysts, in general, characterised by their form or physical properties characterised by their non-solid state in a liquid or molten state
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention belongs to the technical field of preparation of pesticide intermediates, and provides a preparation process of 5-chloro-2, 3-dihydro-1-indanone. 3-chloropropionyl chloride and chlorobenzene are used as raw materials, mixed molten salt of aluminum trichloride, sodium chloride and zinc chloride is used as a catalyst, and a one-pot reaction process is adopted to prepare the product 5-chloro-2, 3-dihydro-1-indanone. The method realizes the liquid-liquid first-step reaction by directly dripping the 3-chloropropionyl chloride and the chlorobenzene raw material into the molten salt at a lower temperature, so that the raw material and the catalyst are easy to disperse and contact, and the stirring is more uniform. The lower molten state temperature of the catalyst also enables the second step reaction to realize liquid-liquid reaction at a relatively lower temperature (130 ℃ -135 ℃), which is beneficial to reducing side reactions and requirements on equipment and energy.
Description
Technical Field
The invention belongs to the technical field of preparation of pesticide intermediates, and particularly relates to a preparation process of 5-chloro-2, 3-dihydro-1-indanone.
Background
5-chloro-2, 3-dihydro-1-indanone is an important intermediate of a new pesticide variety developed by DuPont in 1992, and at present, the synthesis of the product mainly comprises the following methods:
first, a first synthesis method: m-chlorocinnamic acid method.
The method takes m-chloro cinnamic acid as a raw material, obtains m-chloro phenylpropionic acid by hydrogenation, obtains m-chloro phenylpropionyl chloride by chlorination, and finally obtains 5-chloro-2, 3-dihydro-1-indanone by cyclization. The method has the defects that selectivity exists during ring closing, 7-chloro-2, 3-dihydro-1-indanone can be formed in a certain proportion, so that the product is impure and the separation problem exists.
Second, second synthesis method: 3, 4-dichlorophenylacetone synthesis method.
The method takes 3, 4-dichloropropiophenone as a raw material, and 5-chloro-2, 3-dihydro-1-indanone is generated by cyclization. The catalyst used for the cyclization is aluminum trichloride, concentrated sulfuric acid, trifluoromethanesulfonic acid and the like.
The catalyst has respective defects at present, and the problems of overlarge using amount, high cost and high price exist when the trifluoromethanesulfonic acid is used as the catalyst. The problem of carbonization is easily caused in the reaction process by using concentrated sulfuric acid as a catalyst, and generally, dozens of times of equivalent of concentrated sulfuric acid is needed, so that the consumption is too large, the corrosivity is strong, and the pollution is serious. The aluminum chloride is used as a catalyst, and the problems of difficulty in selecting a proper solvent, serious side reaction and the like exist at present.
The preparation of the 3, 4-dichlorophenylacetone mainly comprises two synthetic routes:
one is obtained by Friedel-crafts reaction of 3-chloropropionyl chloride and chlorobenzene in the presence of a catalyst, wherein the used catalyst comprises aluminum trichloride, trifluoromethanesulfonic acid, hydrofluoric acid/boron trifluoride and the like.
Secondly, the 3, 4-dichloropropiophenone can be obtained by catalyzing chlorobenzoyl chloride and ethylene by aluminum trichloride under certain pressure. The ethylene synthesis method has a problem that raw materials are not easily available and pressurization is required although the yield is high, and thus it is difficult to industrially produce the ethylene in a large scale.
3-chloropropionyl chloride and chlorobenzene are used as raw materials to generate 3, 4-dichloropropiophenone through Friedel-crafts acylation reaction, and the 3, 4-dichloropropiophenone is cyclized to generate 5-chloro-2, 3-dihydro-1-indanone through self Friedel-crafts alkylation reaction. The synthesis route is relatively simple and easy to obtain raw materials, reaction conditions are easy to realize, industrialization can be realized, the synthesis route is a common method for preparing 5-chloro-2, 3-dihydro-1-indanone, and the reaction formula is as follows:
the preparation process introduced in the Chinese patent CN1403434A adopts a two-step method: the first step, the Friedel-crafts acylation reaction is carried out on 3-chloropropionyl chloride and chlorobenzene, and then an intermediate 3, 4-dichloropropiophenone is obtained through hydrolysis, separation and purification; secondly, the intermediate is subjected to Friedel-crafts alkylation reaction, and then is hydrolyzed, separated and purified to obtain the 5-chloro-2, 3-dihydro-1-indanone. Two hydrolysis, separation and purification operations are needed before and after the hydrolysis, separation and purification operations, and the consumption and discharge are large. Also, patent CN109293488A discloses that the intermediate is not subjected to hydrolysis, separation and purification steps, but still needs to be reacted in two reactors with different catalysts in two steps, the first step is using aluminum chloride as a catalyst, and the second step is using mixed molten salt as a catalyst. Patent CN103012086B provides a method for preparing 2, 3-dihydro-1-indanone, which, although it realizes the "one-pot" preparation process of two-step reaction, has two disadvantages: firstly, in the first step of Friedel-crafts acylation reaction, catalysts of aluminum trichloride and sodium chloride are solid and have large addition amount at the reaction temperature, no other solvent is used except for raw materials, the reaction is a liquid-solid reaction, a system is viscous along with gradual generation of an intermediate, and the problems of difficult stirring, uneven mixing and the like easily occur. Secondly, because the molten temperature of the molten salt of aluminum trichloride and sodium chloride is higher, the reaction temperature in the second step needs to be controlled to be more than 150 ℃, on one hand, more side reactions are easy to occur, and on the other hand, the requirements on equipment, energy and the like are greatly increased due to the too high temperature.
Disclosure of Invention
The invention aims to overcome the defects of the preparation process of 5-chloro-2, 3-dihydro-1-indanone in the prior art, provides a new one-pot method process for preparing 5-chloro-2, 3-dihydro-1-indanone, and screens out a mixed molten salt catalyst which can be melted at a lower temperature. So that the second step reaction can be carried out in a liquid-liquid reaction mode at a relatively low temperature (130-135 ℃), side reactions are reduced, and requirements on equipment and energy are lowered.
The technical scheme for realizing the purpose of the invention is as follows:
the invention takes 3-chloropropionyl chloride and chlorobenzene as raw materials, takes mixed molten salt as a catalyst and a solvent, the molten salt is mixed molten salt of aluminum chloride, sodium chloride and zinc chloride, the raw materials of 3-chloropropionyl chloride and chlorobenzene react by a one-pot method to obtain 5-chloro-2, 3-dihydro-1-indanone, and the method comprises the following process flows:
a. mixing aluminum chloride, sodium chloride and zinc chloride according to the weight ratio of aluminum chloride: sodium chloride: zinc chloride ═ 1: (0.5-1.5): (0.05-0.1) putting the mixture into a reactor, heating and stirring the mixture to form mixed molten salt, controlling the temperature to be 70-90 ℃, and adding 3-chloropropionyl chloride and chlorobenzene, wherein the adding proportion (molar ratio) of the 3-chloropropionyl chloride, the chlorobenzene and aluminum chloride is 3-chloropropionyl chloride: chlorobenzene: aluminum chloride is 1: (1-2.0): (5-15), carrying out heat preservation reaction, and carrying out nuclear magnetic monitoring reaction until the 3-chloropropionyl chloride is completely converted to generate 3-chloro-1- (4-chlorphenyl) -1-acetone;
b. and raising the temperature of the reaction system to 130-135 ℃, continuing the heat preservation reaction, and monitoring the reaction by nuclear magnetism until the 3-chloro-1- (4-chlorphenyl) -1-acetone is completely converted to generate the 5-chloro-2, 3-dihydro-1-indanone.
Preferably: the adding proportion (molar ratio) of the aluminum chloride, the sodium chloride and the zinc chloride is as follows: sodium chloride: zinc chloride ═ 1: (0.8-1.2): (0.05-0.1).
Further preferably: the proportion (molar ratio) of chlorobenzene to 3-chlorophenylchloride to aluminum trichloride in the step a is 3-chloropropionyl chloride: chlorobenzene: aluminum chloride is 1: (1.0-1.3): (8-10).
Preferably: in the step a, the reaction time is 0.5-4 h, and preferably: the reaction time was 2 hours. In the step b, the reaction time is 2-7 h, and preferably: the reaction time was 3 hours.
And c, after the reaction is finished, adding the reaction solution into a mixture of hydrochloric acid and ice water in a weight ratio of 1: (20-40) extracting the mixture with dichloromethane, washing with alkali, drying, removing the solvent to obtain a crude product, and distilling with steam to obtain the refined 5-chloro-2, 3-dihydro-1-indanone.
The invention has the advantages and beneficial effects that:
the invention prepares the product by a one-pot method, and materials react in the same reactor, thereby saving the steps of hydrolysis, separation and purification of the intermediate in the first step. The technical key for realizing the new preparation process of the one-pot method is to screen out the mixed molten salt catalyst which can be melted at a lower temperature. The zinc chloride additive is added to realize that the molten salt can keep molten state at the temperature as low as 70 ℃, so that the 3-chloropropionyl chloride and chlorobenzene raw materials are directly dripped into the molten salt at a lower temperature to ensure that the first-step acylation reaction is carried out in a liquid-liquid reaction mode, so that the raw materials and the catalyst are more easily dispersed and contacted, and the stirring is more uniform. The lower molten state temperature of the catalyst also enables the second step reaction to be carried out in a liquid-liquid reaction mode at a relatively lower temperature (130 ℃ -135 ℃), which is beneficial to reducing side reactions and requirements on equipment and energy.
Drawings
The accompanying drawings are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, but do not constitute a limitation of the invention. In the drawings:
FIG. 1 is a nuclear magnetic monitoring chart of 3-chloropropionyl chloride converted to an intermediate 3-chloro-1- (4-chlorophenyl) -1-propanone in example 1 of the present invention;
FIG. 2 is a nuclear magnetic monitoring chart of the intermediate 3-chloro-1- (4-chlorophenyl) -1-propanone during the ring-closing reaction in example 1 of the present invention.
Detailed Description
The present invention is further illustrated by the following specific examples, which are intended to be illustrative, not limiting and are not intended to limit the scope of the invention.
In the reaction process, the reaction process is monitored by a nuclear magnetic means, and the specific method comprises the following steps: opening the reaction bottle mouth under the protection of nitrogen, rapidly collecting a small amount of reaction liquid by using a dropper, hydrolyzing the reaction liquid, and then performing nuclear magnetic hydrogen spectrum detection by using a deuterated chloroform dissolved product. And judging whether the reaction is carried out or not and the degree of the reaction according to the characteristic peaks of the raw materials and the products on the nuclear magnetic hydrogen spectrogram. In FIG. 1, 3-chloropropionyl chloride has been converted to 3-chloropropionic acid by hydrolysis, and the peaks of the two groups of hydrogen 1 and 2 of 3-chloropropionic acid and the peaks of the two groups of hydrogen 3 and 4 of 3-chloro-1- (4-chlorophenyl) -1-propanone are therefore compared in the nuclear magnetic diagram. In FIG. 2, two sets of hydrogen peaks for 3-chloro-1- (4-chlorophenyl) -1-propanone, 1 and 2, and two sets of hydrogen peaks for 5-chloro-2, 3-dihydro-1-indanone, 3 and 4, are compared.
Example 1
Under the protection of nitrogen, 40g (300mmol) of aluminum trichloride, 17.5g (300mmol) of sodium chloride and 2.9g (21mmol) of zinc chloride are added into a 250ml three-neck flask, heated and stirred until the mixture is molten, the temperature is controlled at 80 ℃, and a mixed solution of 4.4g (39mmol) of chlorobenzene and 3.8g (30mmol) of 3-chloropropionyl chloride is added. After the dropwise addition, the reaction is carried out for 2h at 80 ℃, and the 3-chloropropionyl chloride is completely converted by nuclear magnetic monitoring to generate the 3-chloro-1- (4-chlorphenyl) -1-acetone. Then the temperature is raised to 130 ℃, the reaction is carried out for 3h at the temperature, and the nuclear magnetism monitors that the intermediate is completely converted to generate the 5-chloro-2, 3-dihydro-1-indanone. The product was poured into hydrochloric acid: ice water 15 g: 450g of hydrochloric acid and ice water mixture is added with dichloromethane to extract the product, the dichloromethane layer is washed by saturated sodium bicarbonate and distilled water respectively, solvent is removed by rotary evaporation to obtain a crude product, and the crude product is distilled by steam to obtain 3.26g of refined product with the yield of 65.2%.
Example 2
The difference from example 1 is that the amount of zinc chloride used is: 2.0g (15mmol), 3.20g of a purified product was obtained, yield 64.0%.
Example 3
The difference from example 1 is that the amount of zinc chloride used is: 4.1g (30mmol), 3.18g of the purified product was obtained, yield 63.7%.
Example 4
The difference from example 1 is that:
1. the amount of sodium chloride used was: 8.8g (150 mmol);
2. controlling the temperature to be 90 ℃;
the yield of the purified product was 3.01g, which was 60.2%.
Example 5
The difference from example 4 is that: the amount of sodium chloride used was: 26.3g (450mmol)
The purified product was obtained in an amount of 2.98g, and the yield was 59.6%.
Example 6
The difference from example 4 is that:
1. the amount of sodium chloride used was: 17.5g (300mmol)
2. Controlling the temperature to be 70 ℃;
the yield of the purified product was 3.20g, which was 64.0%.
Example 7
The difference from example 6 is that: the temperature was controlled at 90 ℃ to obtain 3.19g of a purified product in a yield of 63.8%.
Example 8
The difference from example 6 is that:
1. controlling the temperature to be 80 ℃;
2. a mixture of 8.8g (78mmol) of chlorobenzene and 7.6g (60mmol) of 3-chloropropionyl chloride was added.
The purified product was obtained in an amount of 5.76g, and the yield thereof was 57.6%.
Example 9
The difference from example 8 is that:
a mixture of 2.9g (26mmol) of chlorobenzene and 2.5g (20mmol) of 3-chloropropionyl chloride was added.
The yield of the purified product was 2.20g, which was 66.0%.
Example 10
The difference from example 9 is that:
1. a mixture of 4.4g (39mmol) of chlorobenzene and 3.8g (30mmol) of 3-chloropropionyl chloride was added.
2. The temperature was raised to 180 ℃ and the reaction was carried out at this temperature for 3 h.
The yield of the purified product was found to be 3.16g, 63.2%.
Comparative example 1
The purpose of this comparative example is to demonstrate that the molten salt catalyst of the present invention has a lower curing temperature, so that the first acylation reaction can occur at a relatively lower temperature, and contributes to an improvement in yield.
Proportioning is AlCl3: NaCl: additive 1: 1: 0.1 (molar ratio, wherein AlCl30.1mol) of catalyst was heated and stirred to slowly increase the temperature until melting and the temperature at which melting started was recorded, and then slowly decreased to solidification, and the temperature at which solidification started (i.e., the lowest temperature in the molten state) was recorded. And (3) dropwise adding a mixed solution of 1.27g (0.01mol) of 3-chloropropionyl chloride and 1.24g (0.011mol) of chlorobenzene into the molten salt, wherein the dropwise adding temperature is the lowest temperature at which the catalyst keeps molten state, and continuously carrying out heat preservation reaction for 2 hours after the dropwise adding is finished to generate the 3, 4-dichloropropiophenone. Then heating to 140 ℃, keeping the temperature and reacting for 3 hours to obtain 5-chloro-2, 3-dichloro-1-indanone, and determining the yield by a nuclear magnetic internal standard method, wherein the experimental results are shown in table 1:
TABLE 1 Effect of additives on catalyst melt temperature and catalytic Performance
As can be seen from Table 1, the catalyst, which contained no additive, kept in the molten state at a temperature above 150 ℃ and above the boiling points of the starting materials chlorobenzene and 3-chloropropionyl chloride, failed to undergo the first reaction step in the molten state, and thus had no "one-pot" process yield data for this catalyst. When the additive component in the catalyst is changed, the preparation and the catalytic effect of the catalyst are influenced to a certain extent, and the additive is ZnCl2、CuCl、FeCl2、MgCl2KCl, catalysisThe temperature at which the agent starts to melt is between 110 ℃ and 120 ℃, but the temperature range at which it remains molten is significantly different. The additive is CuCl or FeCl2KCl, when the temperature is reduced to below 100 deg.C, the curing is started, and the additive is ZnCl2And MgCl2In the process, the catalyst is solidified below 70 ℃, so that molten salt with the temperature as low as 70 ℃ can be formed, and the acylation reaction in the first step is facilitated to occur at a relatively low temperature. The additive is ZnCl2The explicit additive is MgCl2The catalyst has better catalytic effect, so the invention selects the catalyst additive which can ensure that the fused salt has lower freezing point and better catalytic effect as ZnCl2。
Comparative example 2
This comparative example is intended to illustrate that the second reaction is susceptible to polymerization side reactions under an aluminum chloride-sodium chloride catalytic system, resulting in poor yields.
Under the protection of nitrogen, 20mL of dichloromethane and 5.33g (40mmol,2equiv.) of aluminum trichloride catalyst are added into a 100mL three-necked flask, and the mixture is stirred for 30min until the catalyst is dispersed in the solvent. Adding 2.48g (22mmol,1.1equiv.) of chlorobenzene, dropwise adding 2.54g (20mmol, 1equiv.) of 3-chloropropionyl chloride at 35 ℃, carrying out heat preservation reaction after the dropwise adding is finished, sampling during the reaction, carrying out nuclear magnetic monitoring, and completely converting the 3-chloropropionyl chloride after 2 hours to generate a 3-chloro-1- (4-chlorophenyl) -1-acetone intermediate. Heating to evaporate dichloromethane, adding a certain equivalent of aluminum trichloride and sodium chloride, gradually heating to a certain temperature, carrying out heat preservation reaction at the temperature, and sampling nuclear magnetism to monitor the conversion rate of the intermediate. After the reaction was stopped, the reaction solution was poured into a mixed solution of hydrochloric acid and ice water to hydrolyze the reaction solution, and many black insoluble substances were generated, which were estimated to be organic polymers by elemental analysis. Adding dichloromethane to dissolve the product, filtering black insoluble substances, washing with dichloromethane for three times, mixing mother liquor, transferring the mother liquor into a separating funnel, standing, layering, separating a water layer, washing an organic layer with saturated sodium bicarbonate aqueous solution and distilled water in sequence, adding anhydrous magnesium sulfate, drying, filtering, removing dichloromethane by rotary evaporation to obtain a crude product, weighing, and calculating the total crude yield of the two-step reaction, wherein the results are as follows:
TABLE 2 reaction of the aluminum chloride-sodium chloride catalyzed intermediate to 5-chloro-2, 3-dihydro-1-indanone
As can be seen from Table 2, the reaction time becomes shorter as the temperature is increased, but side reactions to form black insoluble polymers are liable to occur at reaction temperatures of 150 ℃ or higher, resulting in poor final yields. In the reactions of the listed examples 1 to 10, the black insoluble material described in comparative example 2 was not produced, and the yield after final purification was relatively high.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various changes and modifications can be made without departing from the inventive concept, and these changes and modifications are all within the scope of the present invention.
Claims (6)
1. A preparation process of 5-chloro-2, 3-dihydro-1-indanone takes 3-chloropropionyl chloride and chlorobenzene as raw materials and takes mixed molten salt as a catalyst and a solvent, and is characterized in that: the molten salt is a mixed molten salt of aluminum chloride, sodium chloride and zinc chloride, the raw materials of 3-chloropropionyl chloride and chlorobenzene are reacted by a one-pot method to obtain 5-chloro-2, 3-dihydro-1-indanone, and the method comprises the following process flows of:
a. mixing aluminum chloride, sodium chloride and zinc chloride according to the weight ratio of aluminum chloride: sodium chloride: zinc chloride ═ 1: 0.5-1.5: placing the mixture in a reactor at a molar ratio of 0.05-0.1, heating and stirring to form mixed molten salt, controlling the temperature to be 70-90 ℃, and adding 3-chloropropionyl chloride and chlorobenzene, wherein the adding molar ratio of the 3-chloropropionyl chloride to the chlorobenzene to aluminum chloride is 3-chloropropionyl chloride: chlorobenzene: aluminum chloride is 1: 1-2.0: 5-15, carrying out heat preservation reaction, and carrying out nuclear magnetic monitoring reaction until the 3-chloropropionyl chloride is completely converted to generate 3-chloro-1- (4-chlorphenyl) -1-acetone;
b. and raising the temperature of the reaction system to 130-135 ℃, continuing the heat preservation reaction, and monitoring the reaction by nuclear magnetism until the 3-chloro-1- (4-chlorphenyl) -1-acetone is completely converted to generate the 5-chloro-2, 3-dihydro-1-indanone.
2. The process for preparing 5-chloro-2, 3-dihydro-1-indanone according to claim 1, which comprises: the adding molar ratio of the aluminum chloride to the sodium chloride to the zinc chloride is as follows: sodium chloride: zinc chloride ═ 1: 0.8-1.2: 0.05 to 0.1.
3. The process for preparing 5-chloro-2, 3-dihydro-1-indanone according to claim 1, which comprises: the adding mole ratio of the 3-chloropropionyl chloride to the chlorobenzene to the aluminum chloride in the step a is 3-chloropropionyl chloride: chlorobenzene: aluminum chloride is 1: 1.0-1.3: 8 to 10.
4. The process for preparing 5-chloro-2, 3-dihydro-1-indanone according to claim 1, which comprises: the heat preservation reaction time of the step a is 0.5-4 h, and the heat preservation reaction time of the step b is 2-7 h.
5. The process for preparing 5-chloro-2, 3-dihydro-1-indanone according to claim 1 or 4, characterized in that: the reaction time of the step a is 2 hours, and the reaction time of the step b is 3 hours.
6. The process for preparing 5-chloro-2, 3-dihydro-1-indanone according to claim 1, which comprises: and c, after the reaction is finished, adding the reaction solution into a mixture of hydrochloric acid and ice water in a weight ratio of 1: and (2) extracting the mixture of 20 to 40 with dichloromethane, washing with alkali, drying, removing the solvent to obtain a crude product, and distilling with steam to obtain the refined 5-chloro-2, 3-dihydro-1-indanone.
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| CN103012086A (en) * | 2011-09-26 | 2013-04-03 | 江西阿尔法高科药业有限公司 | Method for preparing 2,3-dihydro-1-indanone and derivative thereof |
| CN109293488A (en) * | 2018-11-14 | 2019-02-01 | 四平市精细化学品有限公司 | A kind of preparation method of 5-chloro-1-indanone |
| CN111454137A (en) * | 2020-03-17 | 2020-07-28 | 山东京博生物科技有限公司 | Synthetic method for improving yield of 5-chloro-1-indanone |
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| CN103012086A (en) * | 2011-09-26 | 2013-04-03 | 江西阿尔法高科药业有限公司 | Method for preparing 2,3-dihydro-1-indanone and derivative thereof |
| CN109293488A (en) * | 2018-11-14 | 2019-02-01 | 四平市精细化学品有限公司 | A kind of preparation method of 5-chloro-1-indanone |
| CN111454137A (en) * | 2020-03-17 | 2020-07-28 | 山东京博生物科技有限公司 | Synthetic method for improving yield of 5-chloro-1-indanone |
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