CN113511971B - 4-halogenated-2-methyl-2-butenoic acid ethyl ester and preparation method thereof - Google Patents
4-halogenated-2-methyl-2-butenoic acid ethyl ester and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title abstract description 6
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 28
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 17
- UNSIKXJBHRTIOD-UHFFFAOYSA-N ethyl 2-hydroxy-2-methylbut-3-enoate Chemical compound CCOC(=O)C(C)(O)C=C UNSIKXJBHRTIOD-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 8
- 238000005658 halogenation reaction Methods 0.000 claims abstract description 8
- 230000002140 halogenating effect Effects 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 239000003054 catalyst Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- WDCCXADRWCXXOR-UHFFFAOYSA-N ethyl 2-methylbut-3-enoate Chemical compound CCOC(=O)C(C)C=C WDCCXADRWCXXOR-UHFFFAOYSA-N 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 11
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 150000007530 organic bases Chemical class 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 5
- SXQCPXKZTFJHQI-UHFFFAOYSA-N 2-hydroxy-2-methylbut-3-enoic acid Chemical compound C=CC(O)(C)C(O)=O SXQCPXKZTFJHQI-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 3
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 3
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 3
- 238000007599 discharging Methods 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 239000012433 hydrogen halide Substances 0.000 claims description 3
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 3
- 238000004321 preservation Methods 0.000 claims description 3
- 238000010791 quenching Methods 0.000 claims description 3
- ATLBQYLERQCFBC-UHFFFAOYSA-N 4-bromo-2-methylbut-2-enoic acid Chemical compound OC(=O)C(C)=CCBr ATLBQYLERQCFBC-UHFFFAOYSA-N 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 230000000171 quenching effect Effects 0.000 claims description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 abstract description 14
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 6
- 238000009776 industrial production Methods 0.000 abstract description 6
- 231100000331 toxic Toxicity 0.000 abstract description 6
- 230000002588 toxic effect Effects 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000001308 synthesis method Methods 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 2
- 239000013067 intermediate product Substances 0.000 description 13
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 10
- 239000002994 raw material Substances 0.000 description 7
- 239000007795 chemical reaction product Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000012467 final product Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 235000005473 carotenes Nutrition 0.000 description 2
- 235000021466 carotenoid Nutrition 0.000 description 2
- 150000001747 carotenoids Chemical class 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 230000036632 reaction speed Effects 0.000 description 2
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- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 229920001567 vinyl ester resin Polymers 0.000 description 2
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BRFRRYWRNMHZJE-UHFFFAOYSA-N 2-methylbut-3-enyl acetate Chemical compound C=CC(C)COC(C)=O BRFRRYWRNMHZJE-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- -1 haloalkenyl ester Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000015094 jam Nutrition 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000003264 margarine Substances 0.000 description 1
- 235000013310 margarine Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- AABBHSMFGKYLKE-UHFFFAOYSA-N propan-2-yl but-2-enoate Chemical class CC=CC(=O)OC(C)C AABBHSMFGKYLKE-UHFFFAOYSA-N 0.000 description 1
- ZHDCHCTZRODSEN-UHFFFAOYSA-N propyl but-2-enoate Chemical compound CCCOC(=O)C=CC ZHDCHCTZRODSEN-UHFFFAOYSA-N 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- IAHFWCOBPZCAEA-UHFFFAOYSA-N succinonitrile Chemical compound N#CCCC#N IAHFWCOBPZCAEA-UHFFFAOYSA-N 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/307—Preparation of carboxylic acid esters by modifying the acid 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
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/62—Halogen-containing esters
- C07C69/65—Halogen-containing esters of unsaturated acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application discloses 4-halogenated-2-methyl-2-ethyl butenoate and a preparation method thereof, and particularly relates to the technical field of chemical intermediate synthesis. A preparation method of 4-halogenated-2-methyl-2-ethyl butenoate comprises the following steps: 2-methyl-3-ethyl butenoate is synthesized into 2-methyl-2-hydroxy-3-ethyl butenoate through oxidation reaction; carrying out halogenation reaction on the ethyl 2-methyl-2-hydroxy-3-butenoate and a halogenating reagent to obtain the ethyl 4-halogeno-2-methyl-2-butenoate. The synthesis method is simple, has high yield, avoids the use of toxic liquid bromine and hydrocyanic acid, and is easy for industrial production.
Description
Technical Field
The application relates to the technical field of chemical intermediate synthesis, in particular to 4-halogenated-2-methyl-2-ethyl butenoate and a preparation method thereof.
Background
Beta-apo-8' -ethyl carotene is also called ethyl apo-carotene or apo-carotene, is an oxygen-containing apo-carotene compound in carotenoid, is mainly applied to coloring of edible oil, margarine, jam, jelly and beverage products in the food industry, and is a high-efficiency carotenoid additive. Because the content of the natural product in the nature is low, no valuable method capable of being extracted from the natural raw materials is found at present, so that the beta-apo-8' -ethyl carotene is mainly produced in a commercial way by a total synthesis method.
4-halo-2-methyl-2-butenoic acid ethyl ester is an important intermediate for synthesizing beta-apo-8' -carotenoic acid ethyl ester and related compounds, and the synthesis thereof has been reported in a series of literature. The main industrialized synthesis methods are the butenenitrile method and the methyl vinyl ketone method.
The methyl vinyl ketone method (US 4937308, DE 3244273) is to take ethanol as a solvent, take methyl vinyl ketone and hydrocyanic acid to carry out addition reaction to synthesize cyanohydrin, introduce dry hydrogen chloride gas to react, hydrolyze under alkaline condition to generate 2-methyl-2-hydroxy-3-ethyl butenoate, and then synthesize 4-halogenated 2-methyl-2-ethyl butenoate with phosphorus tribromide, and the specific route is as follows:
the method needs to use the highly toxic reagent hydrocyanic acid, and has high requirements on equipment and environment.
The butenenitrile method (patent DE3244273A1 and US 4937308A) takes butenenitrile as a raw material, ethanol as a solvent, dry hydrogen chloride gas is introduced to react to generate 2-vinyl propionate, then elemental bromine is added dropwise or chlorine gas is introduced, and then elimination reaction is carried out to synthesize 4-halogeno-2-methyl-2-ethyl butenoate. The reaction route is as follows.
In the technical scheme, the raw material butenenitrile is a byproduct of succinonitrile production, is cheap and easy to obtain, but the trans-content of the product haloalkenyl ester is low (the yield of a bromination route is only about 49%, and the yield of the chlorinated route is 44-46%), the trans-enyl ester is required to be separated and shifted for many times to improve the yield of the trans-enyl ester, in addition, bromine is expensive, the toxicity is high, the route cost is high, the industrialization is not favored, a large amount of chlorine escapes during the reaction, the reaction speed and the quality are influenced, and simultaneously, high requirements on equipment type selection, safety control and tail gas treatment are provided, and the route industrialization application difficulty is increased.
The two methods for synthesizing the 4-halogenated-2-methyl-2-ethyl butenoate commonly used in the industry at present have a series of defects of high toxicity, complex process route, high requirements on production environment and equipment and the like, and are not beneficial to industrial production.
Disclosure of Invention
In order to solve the defects in the art, the application provides 4-halogenated-2-methyl-2-ethyl butenoate and a preparation method thereof, and the synthesis method is simple, has high yield, avoids the use of toxic liquid bromine and hydrocyanic acid, and is easy for industrial production.
According to one aspect of the present application, a process for preparing ethyl 4-halo-2-methyl-2-butenoate comprises the steps of:
(1) 2-methyl-3-ethyl butenoate is synthesized into 2-methyl-2-hydroxy-3-ethyl butenoate through oxidation reaction;
(2) Carrying out halogenation reaction on the ethyl 2-methyl-2-hydroxy-3-butenoate and a halogenating reagent to obtain the ethyl 4-halogeno-2-methyl-2-butenoate.
According to some embodiments of the present application, in the step (1), 2-methyl-3-butenyl acetate is placed in an alcohol solvent containing an organic base, a catalyst is added, an oxygen-containing atmosphere is introduced, and a certain pressure is maintained for oxidation reaction.
According to some embodiments of the present application, the organic base is selected from one or more of triethylamine, dimethylamine, pyridine;
according to some embodiments of the application, the organic base is pyridine;
according to some embodiments of the application, the alcoholic solvent comprises ethanol;
according to some embodiments of the present application, the oxygen-containing atmosphere is air, which is selected as the oxidizing agent, is non-toxic and inexpensive and readily available.
According to some embodiments of the present application, the catalyst is selected from copper-based catalysts;
according to some embodiments of the present application, the catalyst is selected from one or more of copper chloride, copper sulfate, copper nitrate.
According to some embodiments of the present application, the molar ratio of ethyl 2-methyl-3-butenoate to the organic base in the oxidation reaction is 1: (0.015-0.06);
according to some embodiments of the present application, the molar ratio of ethyl 2-methyl-3-butenoate to the catalyst in the oxidation reaction is 1: (0.015-0.03);
according to some embodiments of the present application, the mass ratio of ethyl 2-methyl-3-butenoate to solvent in the oxidation reaction is 2: (2.5-4.5);
according to some embodiments of the present application, the mass ratio of ethyl 2-methyl-3-butenoate to solvent in the oxidation reaction is 2:3.
According to some embodiments of the present application, the oxidation reaction is carried out under stirring for 15-25 hours;
according to some embodiments of the present application, the reaction is 20-21h;
according to some embodiments of the present application, the stirring rate is 800-1200r/min;
according to some embodiments of the present application, 1000r/min.
According to some embodiments of the present application, the temperature of the oxidation reaction is 30-60 ℃;
according to some embodiments of the present application, 30-50 ℃;
according to some embodiments of the present application, the pressure of the oxidation reaction is 0.8 to 1.5MPa;
according to some embodiments of the present application, 0.8-1.2MPa.
According to some embodiments of the present application, after the oxidation reaction is performed under stirring for 15-25 hours, the method further comprises:
cooling to room temperature, and discharging the pressure to normal pressure;
rectifying and separating the reaction filtrate to obtain the 2-methyl-2-hydroxy-3-butenoate.
According to some embodiments of the application, in step (2):
placing the obtained 2-methyl-2-hydroxy-3-butenoate in a reaction vessel, cooling to 0-15 ℃, according to some embodiments of the present application, to 5-10 ℃;
dropwise adding a halogenated reagent under the stirring condition, and controlling the reaction temperature to be 0-20 ℃;
after the addition of the halogenated reagent, the reaction is carried out at 0-20 ℃ for 3-6 hours, and according to some embodiments of the application, the reaction is carried out at 15 ℃ for 4-5 hours.
According to some embodiments of the present application, the halogenated agent is selected from one or more of hydrogen halide, phosphorus tribromide, phosphorus trichloride;
according to some embodiments of the application, the halogenated agent is selected from the group consisting of phosphorus tribromide, phosphorus trichloride.
According to some embodiments of the present application, the molar ratio of the halogenated 2-methyl-2-hydroxy-3-butenoic acid ethyl ester to the halogenated reagent is 1: (1.1-1.2).
According to some embodiments of the present application, the halogenation reaction further comprises:
after the heat preservation reaction is finished, excessive phosphorus tribromide is quenched by dropwise adding water at the temperature of not higher than 20 ℃, and the mixture is stirred, stood and layered to obtain 4-bromo-2 methyl-2-butenoate.
The reaction process comprises the following steps:
the green process for preparing the 4-halogenated-2 methyl-2-ethyl butenoate, which is described in the step (1), avoids the generation of isomerization byproducts.
According to another aspect of the present application, there is provided ethyl 4-halo-2-methyl-2-butenoate prepared by the above process.
Compared with the prior art, the beneficial effects of the application comprise one or more of the following.
According to the embodiment of the application, the synthetic method is obtained by taking the ethyl 2-methyl-3-butenoate as a raw material, and carrying out halogenation reaction after oxidation.
According to the embodiment of the application, the use of expensive and toxic liquid bromine and hydrocyanic acid in the existing synthesis method can be avoided, the use of a large amount of halogen on the butenenitrile route of the C5 phosphate is avoided, the treatment capacity of a large amount of halogen-containing wastewater is reduced, and the safety risk is reduced.
According to the embodiment of the application, air is selected as the oxidant, so that the method is nontoxic, low in cost and easy to obtain.
According to the embodiment of the application, the requirement on synthesis equipment is low, and the industrial production is easy.
According to the embodiment of the application, side reactions can be avoided, and the yield is high, wherein the content of trans-4-bromo-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%.
Drawings
FIG. 1 is a schematic illustration of ethyl 2-methyl-2-hydroxy-3-butenoate according to an exemplary embodiment of the present application 1 H-NMR；
FIG. 2 is an illustration of ethyl 2-methyl-2-hydroxy-3-butenoate according to an exemplary embodiment of the present application 13 C-NMR；
FIG. 3 is a vapor phase detection diagram of ethyl 2-methyl-2-hydroxy-3-butenoate according to an exemplary embodiment of the present application.
Detailed Description
As mentioned above, the main industrialized synthetic methods of 4-halogeno-2-methyl-2-ethyl butenoate are the butenenitrile method and the methyl vinyl ketone method, and the synthetic processes thereof have some disadvantages:
the methyl vinyl ketone method (US 4937308, DE 3244273) requires the use of the highly toxic reagent hydrocyanic acid, and has high requirements on equipment and environment.
The product of the butenenitrile method (patent DE3244273A1 and US 4937308A) has lower trans-form content of halogenated vinyl ester, needs to be separated and shifted for many times to improve the trans-vinyl ester yield, has high bromine price, high toxicity and high route cost, is unfavorable for industrialization, and can lead chlorine to escape in a large amount during the reaction, thereby providing higher requirements for equipment selection, safety control and tail gas treatment and increasing the difficulty of route industrialization application while influencing the reaction speed and quality.
The application aims to provide 4-halogenated-2-methyl-2-ethyl butenoate and a green synthesis process thereof.
The following description of the embodiments of the present application will be made clearly and fully with reference to the embodiments of the present application, and it is apparent that the described embodiments are some, but not all, of the embodiments of the present application. All other embodiments, which can be made by those skilled in the art based on the embodiments herein without making any inventive effort, are intended to be within the scope of the present application.
It is particularly pointed out that similar substitutions and modifications made in relation to the present application will be apparent to a person skilled in the art and are all considered to be included in the present application. It will be apparent to those skilled in the relevant art that modifications and variations can be made in the methods and applications described herein, or in the appropriate variations and combinations, without departing from the spirit and scope of the application. It will be apparent that the described embodiments are only some, but not all, of the embodiments of the present application.
The application is carried out according to the conventional conditions or the conditions suggested by manufacturers if the specific conditions are not noted, and the raw materials or auxiliary materials and the reagents or the equipment are conventional products which can be obtained commercially if the manufacturers are not noted.
According to the technical conception of the application, the 4-halogenated-2-methyl-2-ethyl butenoate and a green process thereof are provided, the synthesis method is simple, the yield is high, the use of toxic liquid bromine and hydrocyanic acid is avoided, the industrial production is easy, and the raw material 2-methyl-3-ethyl butenoate can be obtained by directly alcoholysis of butenenitrile with reference to the existing patent (DE 3244273A1 and US 4937308A).
The present application is described in detail below with reference to the accompanying drawings.
(1) Process for preparing ethyl 4-halo-2-methyl-2-butenoate
Comprising the following steps:
2-methyl-3-ethyl butenoate is used as a raw material to perform oxidation reaction to obtain an intermediate product;
the intermediate product is subjected to halogenation reaction to obtain the 4-halogeno-2-methyl-2-ethyl butenoate.
More specifically, at 30-50 ℃, a proper amount of ethyl 2-methyl-3-butenoate is put into an alcohol solvent containing organic alkali, a catalyst is added, air is introduced, and oxidation reaction is carried out under the pressure of 0.8-1.2MPa to synthesize an intermediate product ethyl 2-methyl-2-hydroxy-3-butenoate;
and (3) carrying out halogenation reaction on the synthesized ethyl 2-methyl-2-hydroxy-3-butenoate and a halogenating reagent at the temperature of 0-20 ℃ to synthesize the ethyl 4-halogeno-2-methyl-2-butenoate.
The reaction avoids isomerization reaction at 30-50 ℃; air is selected to oxidize and pressurize to increase the content of oxygen in the solvent, so that the oxidation reaction is promoted; meanwhile, oxygen in the air is used as an oxidant, and in some cases, the oxygen can react under the condition of oxygen-deficient environment or pure oxygen, but the pure oxygen condition has high risk, and the air belongs to a clean oxidant, and is nontoxic and easy to obtain.
Preferably, the organic base is selected from one of triethylamine, dimethylamine and pyridine; the alcohol solvent comprises ethanol; ethanol is selected as a solvent, so that the occurrence of side reactions of transesterification can be avoided; the action of adding alkali into ethanol comprises: hydrogen is extracted and is used as a ligand of copper.
The halogenated reagent is selected from hydrogen halide, phosphorus tribromide and phosphorus trichloride;
the catalyst is selected from: a copper-based catalyst;
the catalyst is selected from one or more of copper chloride, copper sulfate and copper nitrate; the catalyst plays a role in activating hydrogen and improves selectivity.
Preferably, the mass ratio of the ethyl 2-methyl-3-butenoate to the solvent in the oxidation reaction is 2: (2.5-4.5); the molar ratio of the ethyl 2-methyl-3-butenoate to the catalyst in the oxidation reaction is 1: (0.015-0.03); the molar ratio of the ethyl 2-methyl-3-butenoate to the organic base in the oxidation reaction is 1: (0.015-0.06); the molar ratio of the halogenated 2-methyl-2-hydroxy-3-butenoic acid ethyl ester to the halogenated reagent is 1: (1.1-1.2).
(2) Structural characterization and content determination of intermediate 2-methyl-2-hydroxy-3-butenoic acid ethyl ester
Structural characterization: 1 H-NMR (see FIG. 1)
13 C-NMR (see FIG. 2)
And (3) content measurement: content determination by gas chromatography (see FIG. 3)
Gas phase conditions: detector 250 ℃, sample inlet 250 ℃, column temperature box 80 ℃ constant temperature, chromatographic column DB-1
Example 1
(1) Oxidation reaction: weighing ethyl 2-methyl-3-butenoate, dissolving in an ethanol solvent containing organic alkali, adding a catalyst, and placing in a 2L high-pressure reaction kettle; pressurizing air, heating, stirring at 1000r/min, and reacting at a constant temperature;
(2) And (3) oxidation reaction post-treatment: cooling to room temperature, and discharging the pressure to normal pressure; rectifying and separating the reaction filtrate to obtain an intermediate product of the ethyl 2-methyl-2-hydroxy-3-butenoate, (solvent is rectified and recycled, and the catalyst can be recycled to the next batch reaction after treatment);
(3) Halogenation reaction: placing the separated 2-methyl-2-hydroxy-3-ethyl butenoate into a 1000mL four-necked flask, cooling to 5 ℃, slowly dropwise adding phosphorus tribromide under the stirring of 500r/min, controlling the reaction temperature to be not higher than 10 ℃, and carrying out heat preservation reaction for 4h at 10 ℃. After the reaction is finished, a proper amount of water is slowly added dropwise to quench excessive phosphorus tribromide, the temperature of the reaction liquid is controlled in the quenching process, the mixture is stirred for 30min after the dropwise addition, and the mixture is stood for layering, so that a crude product of 4-bromo-2-methyl-2-ethyl butenoate is obtained.
Specific reaction parameters:
using the parameters set forth above, 210g of intermediate product was obtained, the final product: 290g (wherein the content of trans-4-bromo-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%).
Example 2
The reaction procedure of this example was identical to that of example 1, and some of the reaction condition parameters were adjusted, specifically as shown in the following table:
using the parameters set forth above, 215g of intermediate product, end product: 296g (wherein the content of trans-4-bromo-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%).
Example 3
The reaction procedure of this example was the same as that of example 1, and other reaction condition parameters were adjusted, specifically as shown in the following table:
using the parameters set forth above, 214g of intermediate product and end product were obtained: 295g (wherein the content of trans-4-bromo-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%).
Example 4
The reaction procedure of this example was the same as that of example 1, and other reaction condition parameters were adjusted, specifically as shown in the following table:
using the parameters set forth above, 213g of intermediate product was obtained, the final product: 296g (wherein the content of trans-4-bromo-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%).
Example 5
The reaction procedure of this example was the same as that of example 1, and other reaction condition parameters were adjusted, specifically as shown in the following table:
using the parameters set forth above, 214g of intermediate product and end product were obtained: 297g (wherein the content of trans-4-bromo-2-methyl-2-butenoic acid ethyl ester is not less than 95%).
Example 6
The reaction procedure of this example was the same as that of example 1, and other reaction condition parameters were adjusted, specifically as shown in the following table:
using the parameters set forth above, 213g of intermediate product was obtained, the final product: 235g (wherein the content of trans-4-chloro-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%).
Example 7
The reaction procedure of this example was the same as that of example 1, and other reaction condition parameters were adjusted, specifically as shown in the following table:
using the parameters set forth above, 214g of intermediate product and end product were obtained: 292g (wherein the content of trans-4-bromo-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%).
Example 8
The reaction procedure of this example was the same as that of example 1, and other reaction condition parameters were adjusted, specifically as shown in the following table:
using the parameters set forth above, 214g of intermediate product and end product were obtained: 291g (wherein the content of trans-4-bromo-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%).
Example 9
The reaction procedure of this example was the same as that of example 1, and other reaction condition parameters were adjusted, specifically as shown in the following table:
using the parameters set forth above, 213g of intermediate product was obtained, the final product: 233g (wherein the content of trans-4-chloro-2-methyl-2-butenoic acid ethyl ester is more than or equal to 95%).
In summary, the 4-halogeno-2-methyl-2-ethyl butenoate prepared by the method has high yield, simple process, low toxicity and easy industrial production.
The above description of embodiments is only for aiding in the understanding of the method of the present application and its core ideas. It should be noted that it would be obvious to those skilled in the art that various improvements and modifications can be made to the present application without departing from the principles of the present application, and such improvements and modifications fall within the scope of the claims of the present application.
Claims (13)
1. A process for preparing ethyl 4-halo-2-methyl-2-butenoate comprising the steps of:
(1) Placing the 2-methyl-3-ethyl butenoate into an alcohol solvent containing organic base, adding a catalyst, introducing an oxygen-containing atmosphere, and carrying out oxidation reaction under a certain pressure to synthesize the 2-methyl-2-hydroxy-3-ethyl butenoate;
(2) Carrying out halogenation reaction on 2-methyl-2-hydroxy-3-ethyl butenoate and a halogenating reagent to obtain 4-halogeno-2-methyl-2-ethyl butenoate;
wherein the organic base is selected from one or more of triethylamine, dimethylamine and pyridine;
the catalyst is selected from one or more of copper chloride, copper sulfate and copper nitrate;
the halogenated reagent is selected from one or more of hydrogen halide, phosphorus tribromide and phosphorus trichloride.
2. The method of claim 1, wherein the alcoholic solvent comprises ethanol.
3. The method of claim 1, wherein the oxygen-containing atmosphere is air.
4. The process of claim 1, wherein the molar ratio of ethyl 2-methyl-3-butenoate to the organic base in the oxidation reaction is 1: (0.015 to 0.06).
5. The process according to claim 1 or 4, characterized in that the molar ratio of ethyl 2-methyl-3-butenoate to the catalyst in the oxidation reaction is 1: (0.015 to 0.03).
6. The method according to claim 1 or 4, wherein the mass ratio of ethyl 2-methyl-3-butenoate to solvent in the oxidation reaction is 2: (2.5-4.5).
7. The method according to claim 1, wherein the oxidation reaction is carried out under stirring for 15-25 hours;
the stirring speed is 800-1200r/min.
8. The method according to claim 1, wherein the temperature of the oxidation reaction is 30-50 ℃; the pressure of the oxidation reaction is 0.8-1.2MPa.
9. The method of claim 7, wherein the oxidation reaction is performed for 15-25 hours under stirring, further comprising:
cooling to room temperature, and discharging the pressure to normal pressure;
rectifying and separating the reaction filtrate to obtain the 2-methyl-2-hydroxy-3-butenoate.
10. The method of claim 1, wherein the halogenated agent is selected from the group consisting of phosphorus tribromide, phosphorus trichloride.
11. The method according to claim 1, wherein in step (2):
placing the obtained 2-methyl-2-hydroxy-3-butenoate in a reaction vessel, and cooling to 0-15 ℃;
dropwise adding a halogenated reagent under the stirring condition, and controlling the reaction temperature to be 0-20 ℃;
after the halogenated reagent is added, the reaction is carried out for 3 to 6 hours at the temperature of 0 to 20 ℃.
12. The process according to any one of claims 1 or 10 to 11, wherein the molar ratio of the halogenated ethyl 2-methyl-2-hydroxy-3-butenoate to the halogenated reagent is 1: (1.1 to 1.2).
13. The method as recited in claim 11, further comprising:
quenching excessive halogenated reagent at the temperature of not higher than 20 ℃ after the heat preservation reaction is finished, stirring, standing and layering to obtain 4-bromo-2-methyl-2-butenoate.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4596889A (en) * | 1978-12-04 | 1986-06-24 | Basf Aktiengesellschaft | Preparation of alkenyl-lactic acid esters and the novel esters obtained |
| US4937308A (en) * | 1987-06-12 | 1990-06-26 | Basf Aktiengesellschaft | Preparation of alkyl O,O-dialkyl-γ-phosphonotiglates |
| CN103539666A (en) * | 2013-09-27 | 2014-01-29 | 上虞新和成生物化工有限公司 | Preparation method of 2-methyl-3-butenoic acid ester |
| CN104513164A (en) * | 2013-09-30 | 2015-04-15 | 上虞新和成生物化工有限公司 | 4-halogenated-2-methyl-2-ethyl crotonate preparing method |
-
2021
- 2021-07-14 CN CN202110796147.6A patent/CN113511971B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4596889A (en) * | 1978-12-04 | 1986-06-24 | Basf Aktiengesellschaft | Preparation of alkenyl-lactic acid esters and the novel esters obtained |
| US4937308A (en) * | 1987-06-12 | 1990-06-26 | Basf Aktiengesellschaft | Preparation of alkyl O,O-dialkyl-γ-phosphonotiglates |
| CN103539666A (en) * | 2013-09-27 | 2014-01-29 | 上虞新和成生物化工有限公司 | Preparation method of 2-methyl-3-butenoic acid ester |
| CN104513164A (en) * | 2013-09-30 | 2015-04-15 | 上虞新和成生物化工有限公司 | 4-halogenated-2-methyl-2-ethyl crotonate preparing method |
Non-Patent Citations (2)
| Title |
|---|
| Takashi Ooi et al..Advantage of anaerobic conditions in the highly enantioselective synthesis of α,α-dialkyl-α-amino acids by chiral phase-transfer catalysis.《Synlett》.2001,(第7期),1185-1187. * |
| Takeshi Kitahara et al..SYNTHETIC MICROBIAL CHEMISTRY .19. THE SYNTHESIS OF (-)-SIRENIN, SPERM ATTRACTANT OF THE WATER MOLD ALLOMYCES-MACROGYNUS.《Tetrahedron》.1988,第44卷(第15期),4713-4720. * |
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