CN113024412A - Preparation method of 2,4, 6-trichlorobenzonitrile - Google Patents
Preparation method of 2,4, 6-trichlorobenzonitrile Download PDFInfo
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- CN113024412A CN113024412A CN202110309760.0A CN202110309760A CN113024412A CN 113024412 A CN113024412 A CN 113024412A CN 202110309760 A CN202110309760 A CN 202110309760A CN 113024412 A CN113024412 A CN 113024412A
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- trichlorobenzene
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- trichlorobenzonitrile
- bromination
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- PGODHCIOIPODFE-UHFFFAOYSA-N 2,4,6-trichlorobenzonitrile Chemical compound ClC1=CC(Cl)=C(C#N)C(Cl)=C1 PGODHCIOIPODFE-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- 238000005893 bromination reaction Methods 0.000 claims abstract description 34
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 26
- BAPPAFMEUDJAQI-UHFFFAOYSA-N 2-bromo-1,3,5-trichlorobenzene Chemical compound ClC1=CC(Cl)=C(Br)C(Cl)=C1 BAPPAFMEUDJAQI-UHFFFAOYSA-N 0.000 claims abstract description 25
- XKEFYDZQGKAQCN-UHFFFAOYSA-N 1,3,5-trichlorobenzene Chemical compound ClC1=CC(Cl)=CC(Cl)=C1 XKEFYDZQGKAQCN-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 11
- 239000012074 organic phase Substances 0.000 claims description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 230000031709 bromination Effects 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 239000000706 filtrate Substances 0.000 claims description 10
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-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
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 6
- 238000007333 cyanation reaction Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 claims description 3
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 18
- 239000002904 solvent Substances 0.000 abstract description 9
- 230000007613 environmental effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 13
- 230000009286 beneficial effect Effects 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- XXFFSBRDPQFIPO-UHFFFAOYSA-N 1,3,5-trichloro-2-iodobenzene Chemical compound ClC1=CC(Cl)=C(I)C(Cl)=C1 XXFFSBRDPQFIPO-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- -1 ferric chloride Chemical compound 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 238000004537 pulping Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- NJQRKFOZZUIMGW-UHFFFAOYSA-N 1,3,5-trichloro-2-(chloromethyl)benzene Chemical compound ClCC1=C(Cl)C=C(Cl)C=C1Cl NJQRKFOZZUIMGW-UHFFFAOYSA-N 0.000 description 1
- NATVSFWWYVJTAZ-UHFFFAOYSA-N 2,4,6-trichloroaniline Chemical compound NC1=C(Cl)C=C(Cl)C=C1Cl NATVSFWWYVJTAZ-UHFFFAOYSA-N 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000007265 chloromethylation reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
Abstract
The invention provides a preparation method of 2,4, 6-trichlorobenzonitrile, which comprises the following steps: (1) 1,3, 5-trichlorobenzene is contacted with a brominating reagent in an aprotic solvent to carry out bromination reaction, so as to prepare 2-bromo-1, 3, 5-trichlorobenzene; (2) and (2) contacting the 2-bromo-1, 3, 5-trichlorobenzene with a cyaniding reagent in a dipolar aprotic solvent to carry out a cyaniding reaction, thereby obtaining the 2,4, 6-trichlorobenzonitrile. The invention takes cheap and easily available 1,3, 5-trichlorobenzene as raw material, and carries out bromination reaction and cyanidation reaction in a specific solvent in turn, the conversion rate of the raw material is high, and the invention has the advantages of high yield and purity of 2,4, 6-trichlorobenzonitrile, short route, simple process, low cost, environmental protection and the like.
Description
Technical Field
The invention relates to a preparation method of 2,4, 6-trichlorobenzonitrile, and belongs to the field of chemical synthesis.
Background
Fluorine is the element with the largest electronegativity, and the introduction of fluorine atoms enables the fluorine-containing organic compound to have unique physical properties, chemical properties and physiological activities and to show good chemical stability, surface activity, temperature resistance, corrosion resistance and other characteristics, so that the fluorine-containing material has wide application in the fields of biochemistry, pesticides, functional materials and the like. The 2,4, 6-trichlorobenzonitrile compounds are raw materials of a plurality of fluorine-containing compounds, can be used as intermediates of medicines, pesticides and liquid crystal materials, and have important application value and market prospect.
At present, the synthesis process of 2,4, 6-trichlorobenzonitrile compounds generally has the problems of complex process, high cost, low yield, serious pollution and the like, and has large industrial production limitation.
For example, WO2006044454A1 discloses the use of 2,4, 6-trichloro-1-iodobenzene, Zn (CN)2In Pd (PPH)4In the process for preparing 2,4, 6-trichlorobenzonitrile (reaction formula A) by catalytic reaction, the yield of the 2,4, 6-trichlorobenzonitrile is 84%, the raw material of the 2,4, 6-trichloro-1-iodobenzene used in the process is not easy to obtain, and expensive palladium reagent (Pd (PPH)) is required4) And the production cost is high.
Patent document CN111499540 discloses that 1,3, 5-trichlorobenzene is used as a raw material, chloromethylated to obtain 2,4, 6-trichlorobenzyl chloride, and then ammoxidation is performed under the action of a special ammoxidation catalyst to obtain 2,4, 6-trichlorobenzonitrile (reaction formula B), in the process, the chloromethylation process has low raw material conversion rate, high-temperature distillation is required, the equipment requirement is strict, an ammoxidation catalyst is required in the ammoxidation process, and the defects of long reaction time, incomplete raw material conversion and the like exist.
The document (Chemische Berichte,1894, vol.27, p.3151) discloses that 2,4, 6-trichlorobenzonitrile is prepared by Sandmeymer reaction by using 2,4, 6-trichloroaniline as a raw material, the preparation process is shown as a reaction formula C, the process introduces cyano group by diazotization reaction, and the defects of high cost, large amount of three wastes, serious environmental pollution and the like exist.
Disclosure of Invention
The preparation method of 2,4, 6-trichlorobenzonitrile provided by the invention has the advantages of simple process, low cost, high product yield, environmental protection and the like, and can effectively overcome the defects in the prior art.
The invention provides a preparation method of 2,4, 6-trichlorobenzonitrile, which comprises the following steps: (1) 1,3, 5-trichlorobenzene (or called as sym-trichlorobenzene) contacts with a bromination reagent in an aprotic solvent to carry out bromination reaction, so as to prepare 2-bromo-1, 3, 5-trichlorobenzene; (2) 2-bromo-1, 3, 5-trichlorobenzene is contacted with a cyaniding reagent in a dipolar aprotic solvent to carry out a cyanidation reaction, and 2,4, 6-trichlorobenzonitrile is prepared.
Specifically, the bromination reaction in step (1) is to introduce bromine (Br) atoms into 1,3, 5-trichlorobenzene to prepare 2-bromo-1, 3, 5-trichlorobenzene, and the cyanation reaction in step (2) is to replace-Br on 2-bromo-1, 3, 5-trichlorobenzene with cyano (-CN) to prepare 2,4, 6-trichlorobenzonitrile, and the reaction equation of the preparation process is as follows:
in some embodiments, the brominating reagent includes at least one of liquid bromine and N-bromosuccinimide (NBS), which facilitates an increase in the efficiency of 2,4, 6-trichlorobenzonitrile production, as compared to the use of liquid bromine which facilitates a further increase in product yield.
The inventor researches and discovers that the selection of the solvent has important influence on the bromination reaction process, and the non-protic solvent can ensure the stable operation of the bromination reaction process and improve the conversion rate of the raw materials and the yield of the 2-bromo-1, 3, 5-trichlorobenzene. To further optimize the reaction, in some embodiments, the aprotic solvent comprises at least one of dichloromethane, 1, 2-dichloroethane, chloroform, benzene, toluene, ethylbenzene, chlorobenzene.
In practice, the brominating reagent can be used in excess, which is beneficial to increase the conversion rate of 1,3, 5-trichlorobenzene. For example, in some embodiments, the brominating reagent comprises liquid bromine and/or NBS, the molar ratio of 1,3, 5-trichlorobenzene to brominating reagent is 1: (1.0-2.5), for example, 1:1, 1:1.3, 1:1.5, 1:1.8, 1:2, 1:2.3, 1:2.5 or a range consisting of any two of these ratios; or, the brominating reagent comprises dibromine hydantoin, and the molar ratio of 1,3, 5-trichlorobenzene to the brominating reagent is 1: (0.5-1.25), e.g., 1:0.5, 1:0.8, 1:1, 1:1.25 or ratios thereofAny two of (1) or (b). Typically, bromine molecules (Br) in liquid bromine2) One bromine atom participates in the bromination of 1,3, 5-trichlorobenzene, the other bromine atom forms a byproduct, one bromine atom is contained in NBS, the bromine atom participates in the bromination of 1,3, 5-trichlorobenzene, dibromohydantoin contains two bromine atoms, both the two bromine atoms can participate in the bromination of 1,3, 5-trichlorobenzene, and the molar ratio of each bromination reagent to 1,3, 5-trichlorobenzene is controlled within the range, so that the conversion rate of 1,3, 5-trichlorobenzene can be improved, and the use cost of the reagents is reduced.
According to the present study, the temperature of the bromination reaction can range from 0 ℃ to 50 ℃, e.g., from 0 ℃,1 ℃, 10 ℃, 20 ℃, 30 ℃, 40 ℃, 50 ℃, or any two thereof. In contrast, the control of the bromination reaction temperature within the above range is not only beneficial to improving the selectivity of the bromination reaction and obtaining the 2-bromo-1, 3, 5-trichlorobenzene with higher yield, but also beneficial to the stable operation of the bromination reaction, simultaneously saving energy consumption and being more beneficial to industrial production.
In order to further improve the bromination reaction efficiency, in some embodiments, 1,3, 5-trichlorobenzene is subjected to bromination reaction with a bromination reagent in the presence of a catalyst, and the catalyst may include a soluble salt of ferric iron, such as ferric chloride, and the like.
Specifically, 1,3, 5-trichlorobenzene is dissolved in a solvent, a catalyst is added into the solvent, the temperature is raised to the bromination reaction temperature, a bromination reagent is dropwise added into the solvent, the bromination reaction temperature is maintained after the dropwise addition is completed, the bromination reaction can be continued, the bromination reaction can be tracked by High Performance Liquid Chromatography (HPLC), when the ratio of the peak area of the 1,3, 5-trichlorobenzene in the reaction system to the peak area of the 1,3, 5-trichlorobenzene in the system before the bromination reaction is less than or equal to 2.0%, the bromination reaction is considered to be completed, the system is cooled to room temperature, an aqueous solution is added into the system to carry out quenching reaction, the system is kept stand and layered, an organic phase (marked as a first organic phase) is separated, and the first organic phase is washed 1-3 times or more by using an aqueous solution (i.e., the aqueous solution is added into the first organic phase is repeated 1-3 times or more), and the first organic Layer-organic phase separation process), drying and concentrating the finally obtained first organic phase, and in the drying and concentrating process, the 2-bromo-1, 3, 5-trichlorobenzene is gradually crystallized and separated from the organic phase, so as to prepare the 2-bromo-1, 3, 5-trichlorobenzene product (usually a light yellow solid), and through the preparation process, the yield of the 2-bromo-1, 3, 5-trichlorobenzene product can generally reach more than 97%, and the purity can reach more than 94%, so that the subsequent cyanidation reaction is facilitated, and the yield and the purity of the 2,4, 6-trichlorobenzonitrile are improved. Alternatively, the aqueous solution may include an aqueous sodium bisulfite solution and/or a saturated saline solution.
In some embodiments, the cyaniding reagent includes at least one of cuprous cyanide, zinc cyanide, and sodium cyanide, which is beneficial to improve the preparation efficiency of 2,4, 6-trichlorobenzonitrile, and relatively speaking, the use of cuprous cyanide can further improve the yield of 2,4, 6-trichlorobenzonitrile, and compared with cyaniding reagents such as sodium cyanide, cuprous cyanide is less toxic, cheap and easily available, and can further reduce pollution and cost.
According to further research of the inventor, the protonic solvent contains protons such as active hydrogen and is not beneficial to the cyanation reaction, and the nonpolar solvent (the dielectric constant is less than 15, and the dipole moment is 0-6.67 [ (])-30) Without donating protons) is also disadvantageous for the cyanation reaction, and the limited solubility of the two in the raw materials of the cyanating reagent, etc., limits its application in the preparation system of the present invention to some extent, while dipolar aprotic solvents (or dipolar solvents, dielectric constant greater than 15, dipole moment greater than 8.34 (e)-30) Not easy to give protons) has good solubility for raw materials such as cyaniding reagents and the like, and is favorable for the cyaniding reaction. To further optimize the selectivity of the cyanation reaction, increase the yield of 2,4, 6-trichlorobenzonitrile, and the like, in some preferred embodiments, the dipolar aprotic solvent includes at least one of N, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, sulfolane, N-methylpyrrolidone, hexamethylphosphoric triamide.
In specific implementation, the excess of the cyaniding reagent can be realized, which is beneficial to improving the conversion rate of the raw materials. For example, in some embodiments, the molar ratio of 2-bromo-1, 3, 5-trichlorobenzene to cyanating agent is 1: (1.0 to 3.0) means that the molar ratio of 2-bromo-1, 3, 5-trichlorobenzene to cyano groups in the cyanating reagent is 1: (1.0 to 3.0), for example, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2, 1:2.2, 1:2.5, 1:2.8, 1:3 or a range consisting of any two of these values.
As a further study, the temperature of the cyanidation reaction can range from 100 ℃ to 200 ℃, such as, but not limited to, 100 ℃, 120 ℃, 140 ℃, 160 ℃, 180 ℃, 200 ℃, or any two of these values. In contrast, the control of the temperature of the cyanidation reaction within the above range is not only beneficial to improving the selectivity of the cyanidation reaction and obtaining the 2,4, 6-trichlorobenzonitrile with higher yield, but also beneficial to the stable operation of the cyanidation reaction, simultaneously saving the energy consumption and being more beneficial to the industrial production.
In specific implementation, the cyanidation reaction may be tracked by HPLC, and after the 2-bromo-1, 3, 5-trichlorophenyl group is completely converted, that is, the cyanidation reaction is completed (the cyanidation reaction time is generally 4 to 8 hours), the present invention may further perform a purification treatment on a mixed system obtained after the cyanidation reaction is completed, so as to improve the purity of the 2,4, 6-trichlorobenzonitrile, for example, in some embodiments, the preparation process may further include: and (3) cooling the mixed system obtained after the cyanation reaction is finished to room temperature, adding an organic solvent into the mixed system, filtering to obtain a filtrate, adding ammonia water into the filtrate for extraction and separation to respectively obtain a water phase and an organic phase (denoted as a second organic phase), and sequentially crystallizing and recrystallizing the second organic phase to obtain the 2,4, 6-trichlorobenzonitrile. Through the preparation process, the yield of the 2,4, 6-trichlorobenzonitrile product can generally reach more than 68%, and the purity can reach more than 97%.
Optionally, the crystallization and recrystallization process comprises: carrying out reduced pressure concentration on the second organic phase, and gradually crystallizing and separating out the 2,4, 6-trichlorobenzonitrile from the second organic phase in the reduced pressure concentration process to obtain a crude product of the 2,4, 6-trichlorobenzonitrile; and mixing the crude product with an organic solvent, and then recrystallizing to obtain the 2,4, 6-trichlorobenzonitrile product.
In the present invention, the organic solvent may include at least one of petroleum ether, ethyl acetate, n-hexane, n-heptane, toluene, chlorobenzene, 1, 2-dichloroethane, dichloromethane, acetonitrile, acetone, ethanol, and methanol.
The preparation method provided by the invention takes cheap and easily-obtained 1,3, 5-trichlorobenzene as a raw material, and carries out bromination reaction and cyanidation reaction in a specific solvent in sequence, the conversion rate of the raw material is high, the specific expression is that the yield and the purity of 2,4, 6-trichlorobenzonitrile can be higher, the amount of three wastes generated is less, the preparation method is more environment-friendly and safe, the preparation process is carried out in a solvent system, complicated procedures such as diazotization reaction and the like are not needed, the process flow is simple, the requirements on equipment are not strict, the used raw materials/reagents are simple and easily-obtained, and the preparation method has the advantages of high yield and purity of target products, short route, simple process, low cost, environment friendliness and the like, and has important significance for practical industrial application.
Detailed Description
In order to make the technical solutions of the present invention more clearly and completely understandable to those skilled in the art, the following embodiments are described in detail, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, rather than all embodiments, and all other embodiments obtained by those skilled in the art without making any inventive idea should fall within the scope of the present invention.
Unless otherwise specified, the material ratios/percentages used in the following examples are in weight units, and the raw materials and auxiliary materials used are industrial grade materials.
Example 1
(1) Synthesis of 2-bromo-1, 3, 5-trichlorobenzene
Dissolving sym-trichlorobenzene (100 g, 1.00 eq) in dry dichloromethane (1200 ml), adding ferric chloride, heating to 20-30 deg.C, adding dropwise liquid bromine (96.8 g, 1.1 eq), after the dropwise addition, continuously maintaining the temperature at 20-30 ℃, reacting for 5 hours (HPLC detects that the reaction raw material is less than or equal to 2.0 percent), cooling to room temperature, pouring the reaction system into 15 percent sodium bisulfite solution (600 grams) for quenching reaction, standing and layering, the organic phase was separated, washed with a 15% aqueous solution of sodium bisulfite (300 g) and saturated brine (500 g), and then allowed to stand for demixing, followed by separation of the organic phase again, and the separated organic phase was dried and concentrated to give 2-bromo-1, 3, 5-trichlorobenzene as a product (pale yellow solid, about 140.4 g) in 97.79% yield and 94.50% purity.
(2) Synthesis of 2,4, 6-trichlorobenzonitrile
Adding the 2-bromo-1, 3, 5-trichlorobenzene product (70 g, 1.00 eq) into a reaction bottle, adding dried N, N-dimethylformamide (350 ml), adding cuprous cyanide (28.90 g, 1.20 eq) into the reaction bottle under the stirring state, then heating the reaction bottle in an oil bath to 150 ℃ for bromination reaction, and reacting for 6 hours (tracking the 2-bromo-1, 3, 5-trichlorobenzene to be basically completely reacted by HPLC) to obtain a mixed system; cooling the mixed system to room temperature, adding ethyl acetate (700 ml), stirring for 1.0-2.0 hours, fully mixing, and then filtering by using a Buchner funnel filled with diatomite to remove insoluble solids; adding a small amount of ethyl acetate into the obtained filtrate, pulping and washing, adding 25% ammonia water into the filtrate, performing extraction separation, and separating out an organic phase; drying the organic phase by adopting anhydrous sodium sulfate, then filtering, and carrying out reduced pressure concentration (namely crystallization) on the obtained filtrate to obtain a crude product of the 2,4, 6-trichlorobenzonitrile; the crude 2,4, 6-trichlorobenzonitrile product was then slurried (recrystallized) with n-heptane, filtered and dried to give a solid product of 2,4, 6-trichlorobenzonitrile (about 37.80 g as a solid) with a purity of 97.5% and a yield of 68.1%.
The reaction equation in the synthesis process is as follows:
example 2
(1) Synthesis of 2-bromo-1, 3, 5-trichlorobenzene
Dissolving sym-trichlorobenzene (150 g, 1.0 eq) in dry dichloromethane (1200 ml), adding ferric chloride, heating to 20-30 deg.C, adding dropwise liquid bromine (158.2 g, 1.2 eq), after the dropwise addition, continuously maintaining the temperature at 20-30 ℃, reacting for 5 hours (HPLC detects that the reaction raw material is less than or equal to 2.0 percent), cooling to room temperature, pouring the reaction system into 15 percent sodium bisulfite solution (900 g) for quenching reaction, standing and layering, the organic phase was separated, washed with a 15% aqueous solution of sodium bisulfite (450 g) and saturated brine (750 g), allowed to stand for demixing, and the organic phase was separated again and dried and concentrated to give 2-bromo-1, 3, 5-trichlorobenzene as a product (pale yellow solid, about 211.4 g) in 98.20% yield and 96.20% purity.
(2) Synthesis of 2,4, 6-trichlorobenzonitrile
Adding the 2-bromo-1, 3, 5-trichlorobenzene product (120 g, 1.00 eq) into a reaction bottle, adding dry N, N-dimethylformamide (600 ml), adding cuprous cyanide (61.9 g, 1.50 eq) into the reaction bottle under a stirring state, then heating the reaction bottle in an oil bath to 150 ℃ for bromination reaction for 6 hours (tracking the 2-bromo-1, 3, 5-trichlorobenzene to be completely reacted by HPLC), and obtaining a mixed system; cooling the mixed system to room temperature, adding ethyl acetate (1200 ml), stirring for 1.0-2.0 hours, fully mixing, and then filtering by using a Buchner funnel filled with diatomite to remove insoluble solids; adding a small amount of ethyl acetate into the obtained filtrate, pulping and washing, adding 25% ammonia water into the filtrate, performing extraction separation, and separating out an organic phase; drying the organic phase by adopting anhydrous sodium sulfate, then filtering, and carrying out reduced pressure concentration (namely crystallization) on the obtained filtrate to obtain a crude product of the 2,4, 6-trichlorobenzonitrile; the crude 2,4, 6-trichlorobenzonitrile product was then slurried (recrystallized) with n-heptane, filtered and dried to give a solid product of 2,4, 6-trichlorobenzonitrile (about 72.3 g as a solid) with 97.8% purity and 76% yield.
The above detailed description of the preferred embodiments of the present invention and experimental verification. It should be understood that numerous modifications and variations can be devised by those skilled in the art in light of the present teachings without departing from the spirit or scope of the invention. Therefore, the technical solutions available to those skilled in the art through logic analysis, reasoning and limited experiments based on the prior art according to the concept of the present invention should be within the scope of protection defined by the claims.
Claims (10)
1. A preparation method of 2,4, 6-trichlorobenzonitrile is characterized by comprising the following steps:
(1) 1,3, 5-trichlorobenzene is contacted with a brominating reagent in an aprotic solvent to carry out bromination reaction, so as to prepare 2-bromo-1, 3, 5-trichlorobenzene;
(2) and (2) contacting the 2-bromo-1, 3, 5-trichlorobenzene with a cyaniding reagent in a dipolar aprotic solvent to carry out a cyaniding reaction, thereby obtaining the 2,4, 6-trichlorobenzonitrile.
2. The method of claim 1, wherein the brominating reagent comprises at least one of liquid bromine, N-bromosuccinimide, or dibromohydantoin.
3. The production method according to claim 1 or 2, wherein the aprotic solvent comprises at least one of dichloromethane, 1, 2-dichloroethane, chloroform, benzene, toluene, ethylbenzene, and chlorobenzene.
4. The production method according to claim 1 or 2,
the bromination reagent comprises liquid bromine and/or N-bromosuccinimide, and the molar ratio of the 1,3, 5-trichlorobenzene to the bromination reagent is 1: (1.0-2.5);
or, the bromination reagent comprises dibromohydantoin, and the molar ratio of the 1,3, 5-trichlorobenzene to the bromination reagent is 1: (0.5 to 1.25).
5. The method of claim 1 or 2, wherein the bromination reaction is carried out at a temperature of 0 ℃ to 50 ℃.
6. The method of claim 1, wherein the cyaniding agent includes at least one of cuprous cyanide, zinc cyanide, and sodium cyanide.
7. The method of claim 1 or 6, wherein the dipolar-aprotic solvent comprises at least one of N, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, sulfolane, N-methylpyrrolidone, hexamethylphosphoric triamide.
8. The process according to claim 1 or 6, wherein the molar ratio of 2-bromo-1, 3, 5-trichlorobenzene to cyanating agent is 1: (1.0-3.0).
9. The process according to claim 1 or 6, wherein the temperature of the cyanation reaction is 100 ℃ to 200 ℃.
10. The method of claim 1, further comprising: cooling the mixed system obtained after the cyanidation reaction is finished to room temperature, adding an organic solvent into the mixed system, and filtering to obtain a filtrate; and adding ammonia water into the filtrate for extraction separation to respectively obtain a water phase and an organic phase, and sequentially crystallizing and recrystallizing the organic phase to obtain the 2,4, 6-trichlorobenzonitrile.
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