CN116178294A - Method for preparing 5, 5-dimethyl-4, 5-dihydro-isoxazole - Google Patents
Method for preparing 5, 5-dimethyl-4, 5-dihydro-isoxazole Download PDFInfo
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- DIYSFZUJSGOINT-UHFFFAOYSA-N 5,5-dimethyl-4h-1,2-oxazole Chemical compound CC1(C)CC=NO1 DIYSFZUJSGOINT-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 claims abstract description 19
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- 239000003377 acid catalyst Substances 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 13
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 11
- 150000002443 hydroxylamines Chemical class 0.000 claims abstract description 11
- SEPQTYODOKLVSB-UHFFFAOYSA-N 3-methylbut-2-enal Chemical compound CC(C)=CC=O SEPQTYODOKLVSB-UHFFFAOYSA-N 0.000 claims abstract description 10
- ACWQBUSCFPJUPN-UHFFFAOYSA-N Tiglaldehyde Natural products CC=C(C)C=O ACWQBUSCFPJUPN-UHFFFAOYSA-N 0.000 claims abstract description 5
- JDYQJSJLIJQMCW-UHFFFAOYSA-N N-(3-methylbut-2-enylidene)hydroxylamine Chemical compound CC(=CC=NO)C JDYQJSJLIJQMCW-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000009471 action Effects 0.000 claims abstract description 4
- 239000003791 organic solvent mixture Substances 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 239000011964 heteropoly acid Substances 0.000 claims description 3
- JZSKWOFOVWVHFZ-UHFFFAOYSA-N molybdenum phosphoric acid Chemical compound [Mo].OP(O)(O)=O JZSKWOFOVWVHFZ-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 239000006227 byproduct Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000002699 waste material Substances 0.000 abstract description 2
- 238000004821 distillation Methods 0.000 description 11
- 239000012043 crude product Substances 0.000 description 9
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 239000004009 herbicide Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000002363 herbicidal effect Effects 0.000 description 4
- ZNBNBTIDJSKEAM-UHFFFAOYSA-N 4-[7-hydroxy-2-[5-[5-[6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-2-methyl-3-propanoyloxypentanoic acid Chemical compound C1C(O)C(C)C(C(C)C(OC(=O)CC)C(C)C(O)=O)OC11OC(C)(C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CC1 ZNBNBTIDJSKEAM-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 229910000378 hydroxylammonium sulfate Inorganic materials 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- YMCWJQIZJIKFHO-UHFFFAOYSA-N 3-chloro-5,5-dimethyl-4h-1,2-oxazole Chemical compound CC1(C)CC(Cl)=NO1 YMCWJQIZJIKFHO-UHFFFAOYSA-N 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- MFSWTRQUCLNFOM-SECBINFHSA-N haloxyfop-P-methyl Chemical group C1=CC(O[C@H](C)C(=O)OC)=CC=C1OC1=NC=C(C(F)(F)F)C=C1Cl MFSWTRQUCLNFOM-SECBINFHSA-N 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- MFSWTRQUCLNFOM-UHFFFAOYSA-N methyl 2-(4-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}phenoxy)propanoate Chemical group C1=CC(OC(C)C(=O)OC)=CC=C1OC1=NC=C(C(F)(F)F)C=C1Cl MFSWTRQUCLNFOM-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000009333 weeding Methods 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- WVQBLGZPHOPPFO-UHFFFAOYSA-N 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(1-methoxypropan-2-yl)acetamide Chemical compound CCC1=CC=CC(C)=C1N(C(C)COC)C(=O)CCl WVQBLGZPHOPPFO-UHFFFAOYSA-N 0.000 description 1
- JQZGUQIEPRIDMR-UHFFFAOYSA-N 3-methylbut-1-yn-1-ol Chemical compound CC(C)C#CO JQZGUQIEPRIDMR-UHFFFAOYSA-N 0.000 description 1
- DHTHKMKVJRYFPK-UHFFFAOYSA-N 5,5-dimethyl-1,2-oxazolidine Chemical compound CC1(C)CCNO1 DHTHKMKVJRYFPK-UHFFFAOYSA-N 0.000 description 1
- VTNQPKFIQCLBDU-UHFFFAOYSA-N Acetochlor Chemical compound CCOCN(C(=O)CCl)C1=C(C)C=CC=C1CC VTNQPKFIQCLBDU-UHFFFAOYSA-N 0.000 description 1
- 208000003643 Callosities Diseases 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
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- 231100000719 pollutant Toxicity 0.000 description 1
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention provides a method for preparing 5, 5-dimethyl-4, 5-dihydro-isoxazole, which comprises the following steps: (a) Reacting the compound I in the solvent with hydroxylamine salt under the action of an alkaline catalyst to obtain an organic solvent mixture containing the compound III; the compound I is 3-methyl-2-butenal, and the compound III is 3-methyl-2-butenal oxime; (b) And (3) carrying out cyclization reaction on the compound III under the condition of an acid catalyst to obtain the 5, 5-dimethyl-4, 5-dihydro isoxazole. The raw materials are low in price, easy to store, high in cyclization conversion rate and easy to realize industrial production; the target compound can be successfully produced without using any ketoxime, the production of byproducts and waste can be suppressed, and the atomic efficiency can be improved; the target compound is efficiently produced by a simple operation using an inexpensive catalyst.
Description
Technical Field
The invention belongs to the field of organic synthesis, relates to a synthesis method of an important intermediate of haloxyfop-methyl, and in particular relates to a green synthesis method of 5, 5-dimethyl-4, 5-dihydro isoxazole, which has high reaction conversion rate, few byproducts and no pollutants.
Background
WO2002/062770 discloses a useful herbicide, haloxyfop-R-methyl, which is a herbicide with excellent herbicidal activity. The haloxyfop-R-methyl is a biosynthesis inhibitor of extremely long side chain fatty acid in plants, and can effectively prevent and remove grassy weeds and broadleaf weeds in wheat, corn and soybean fields. The herbicide has the characteristics of low dosage per unit area, good weeding effect and long weeding duration, is the biggest, has the possibility of replacing conventional herbicides such as metolachlor, acetochlor and the like in the future, and has good application prospect in crops such as soybeans, corns and the like in China.
JP2013512202A discloses that 5, 5-dimethyl-4, 5-dihydroisoxazole is an important intermediate for herbicides; namely, the 5, 5-dimethyl-dihydro-isoxazole is an important intermediate for preparing the haloxyfop-methyl, and has the structure as follows: . In the existing synthesis report (1006-0413 (2013) 09-0642-03) of the fenpyr-diethyl, 3-chloro-5, 5-dimethyl-4, 5-dihydro-isoxazole is mainly used as an intermediate, and the research of the synthesis route of the 5, 5-dimethyl-4, 5-dihydro-isoxazole is particularly important by using different transformation synthesis methods of an isoxazole ring structure as a main structure. In JP2013512202A, methylbutynol is used as a starting material, isopentylaldehyde is obtained through high-temperature conversion and then cyclized with acetone oxime to obtain 5, 5-dimethyl-4, 5-dihydro-isoxazole, and then 3-chloro-5, 5-dimethyl-4, 5-dihydro-isoxazole is obtained through chlorination. The method has moderate synthetic route length, but the byproduct ketone generated by cyclization has low purity, large purification difficulty and large environment-friendly treatment pressure, and cannot realize industrial production.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a method for preparing 5, 5-dimethyl-4, 5-dihydro-isoxazole.
In order to achieve the technical problems, the invention provides a method for preparing 5, 5-dimethyl-4, 5-dihydro-isoxazole, which comprises the following steps:
(a) Reacting the compound I in the solvent with hydroxylamine salt under the action of an alkaline catalyst to obtain an organic solvent mixture containing the compound III; the compound I is 3-methyl-2-butenal, and the compound III is 3-methyl-2-butenal oxime;
(b) And (3) carrying out cyclization reaction on the compound III under the condition of an acid catalyst to obtain the 5, 5-dimethyl-4, 5-dihydro isoxazole.
Optimally, in the step (a), the alkaline catalyst is a mixture of one or more selected from sodium hydroxide, potassium hydroxide and ammonia. That is, the basic catalysts may be used alone, or in any combination of two or more in any ratio. The base may be of any form as long as the reaction proceeds.
Optimally, in step (a), the mass ratio of the basic catalyst to the hydroxylamine salt is about 1 to 1.2:1.1. the basic catalyst is preferably ammonia; the basic catalyst may be in a slight excess, and the mass ratio of the basic catalyst to hydroxylamine salts such as hydroxylamine hydrochloride/hydroxylamine sulfate is 1:1.1 to adjust the pH to 6.7-7.
Further, in the step (a), the solvent is a mixture of one or more selected from the group consisting of water, acetonitrile, toluene, xylene and methylene chloride; acetonitrile is preferred.
Still further, in step (a), the molar ratio of the compound I to the hydroxylamine salt is 1:1 to 1.5; the temperature of the reaction is 10-70 ℃, preferably the reaction temperature of the cyclization reaction is 10-30 ℃; too high a temperature promotes side reactions. The reaction time is 1 h-24 h.
Optimally, in the step (b), the acid catalyst may be any existing acid catalyst, and a preferable specific example is a mixture of one or more selected from the group consisting of heteropolyacid, phosphotungstic acid, molybdenum phosphoric acid and maleic acid.
Further, in the step (b), the molar amount of the acid catalyst is 10 to 100% of the molar amount of the compound I.
Further, in the step (b), the reaction temperature of the cyclization reaction is 20-80 ℃; preferably 20℃to 30 ℃.
Further, in the step (b), the reaction time of the cyclization reaction is 1 to 48 hours, preferably 36 to 48 hours.
In the above steps (a) and (b), the compound I, the hydroxylamine salt, the basic catalyst and the solvent may be mixed in any order of addition, and in order to allow the reaction raw materials to be converted more rapidly and efficiently, it is preferable to mix the solvent and the hydroxylamine salt, then add the basic catalyst and then add the compound I; the reactants may be added in one portion, or may be added in portions or continuously for better mixing uniformity.
After the cyclization reaction of the step (b), carrying out reduced pressure distillation and purification on the organic phase to obtain a target product, wherein the liquid phase content is more than 90%, the yield can be more than 80%, if the purity is required to be improved, the method can be used for washing with saturated sodium bicarbonate aqueous solution, separating liquid, extracting (anhydrous methanol), merging the organic phase, concentrating the liquid phase content to be more than 95%, and the distilled solvent can be recycled.
The method for preparing 5, 5-dimethyl-4, 5-dihydro-isoxazole has the following advantages:
(1) The raw materials are low in price, easy to store, high in cyclization conversion rate and easy to realize industrial production; the target compound can be successfully produced without using any ketoxime, the production of byproducts and waste can be suppressed, and the atomic efficiency can be improved; the target compound is efficiently produced by a simple operation using an inexpensive catalyst;
(2) The reaction condition is mild, the excessive temperature and pressure are not needed, the reaction operation is simple and convenient, the requirements on equipment are low, and the safety coefficient is greatly increased;
(3) The post-treatment is simple, and the acid catalyst can be recycled by filtering the organic phase after the reaction is finished; the organic solvent used for oxime formation and cyclization can be the same solvent, and the organic phase is recovered by reduced pressure distillation for cyclic solvent application, so that the pollution is less, the post-treatment cost is greatly reduced, and the method is very suitable for industrial mass production;
therefore, the method of the invention is industrially, economically and environmentally desirable and has high industrial utility value.
Drawings
FIG. 1 is a chemical reaction scheme of a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole of the present invention;
FIG. 2 is a process flow diagram of the process of the present invention for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole.
Detailed Description
The invention will be further described with reference to examples of embodiments shown in the drawings.
Example 1
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, as shown in fig. 1 and 2, comprising the steps of:
(a) Reacting a compound I (3-methyl-2-butenal) in a solvent with hydroxylamine salt (compound II) under the action of an alkaline catalyst to obtain an organic solvent mixture containing a compound III (3-methyl-2-butenal oxime) (namely oxime reaction): to a 250ml flask was added 120ml acetonitrile, 34.75g (0.5 mol) hydroxylamine hydrochloride, followed by ammonia gas for 20min (flow rate 4L/min); cooling by ice bath, and dropwise adding 42g (0.5 mol) of 3-methyl-2-butenal into the system after cooling to 5 ℃, wherein the temperature in the dropwise adding process is controlled below 30 ℃ and the dropwise adding time is controlled at 2h; after the completion of the dropwise addition, stirring was carried out at room temperature for 3 hours, and the reaction was completed to obtain an organic phase.
(b) The compound III undergoes cyclization under the condition of an acid catalyst to obtain 5, 5-dimethyl-4, 5-dihydro isoxazole: the aforementioned organic phase (150 ml) was charged into a 250ml flask, and phosphotungstic acid (H) was added in portions at room temperature 5 O 40 PW 12 ) 28.8g (0.1 mol) were stirred at 30℃for 48h. Centrifuging to recover phosphotungstic acid after the reaction is completed, adding 30ml of saturated sodium bicarbonate solution into the product solution after the phosphotungstic acid is recovered, stirring, layering and separating; the aqueous layer was extracted with 20ml of anhydrous methanol, separated, and the organic phases were combined and concentrated under reduced pressure to give a crude product, which was purified by distillation under reduced pressure to give 41.21g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oil), and gas chromatography analysis of the reaction mixture showed that the content of the objective product such as the discharged solvent was 97.4%, yield was 81.1%.
Example 2
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in step (b), the acid catalyst employed is a heteropolyacid; the crude product was purified by distillation under reduced pressure to give 40.98g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oil) in an amount of 97.0% and a yield of 80.3%.
Example 3
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in step (a), 0.75mol of hydroxylamine hydrochloride is added; the crude product was purified by distillation under reduced pressure to give 41.40g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oil) with a content of 97.6% and a yield of 81.7%.
Example 4
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in step (a), hydroxylamine hydrochloride 0.65mol is added; the crude product was purified by distillation under reduced pressure to give 41.25g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oil), content: the yield was 80.99% at 97.2%.
Example 5
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in step (a), hydroxylamine sulfate 0.5mol was added; the crude product was purified by distillation under reduced pressure to give 40.82g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oil) with a content of 96.25% and a yield of 79.36%.
Comparative example 1
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in the step (a), after the dripping is finished, the temperature is raised to 80 ℃ for reaction; the crude product was purified by distillation under reduced pressure to give 41.58g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oil) with a content of 87.6% and a yield of 73.6%.
Comparative example 2
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 5 except that: in the step (a), 41g (0.25 mol) of hydroxylamine sulfate was added, and the crude product was purified by distillation under reduced pressure to give 40.5g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oil) with a content of 95.3% and a yield of 78%.
Comparative example 3
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in step (b), a cyclization reaction is carried out at 90 ℃; the crude product was purified by distillation under reduced pressure to give 43.16g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oily substance), content 72.6%, yield 87.6%
Comparative example 4
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in the step (a), ammonia gas is not introduced, and a product cannot be obtained.
Comparative example 5
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in step (b), the acid catalyst used is molybdenum phosphoric acid (H 5 Mo12O 41 P) 18.25g (0.1 mol); the crude product was purified by distillation under reduced pressure to give 41.15g of 5, 5-dimethyl-4, 5-dihydroisoxazole (colorless oil) with a content of 94.3% and a yield of 78.4%.
Comparative example 6
This example provides a process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole, which is substantially the same as in example 1 except that: in step (b), the product cannot be obtained without using an acid catalyst.
The above embodiments are provided to illustrate the technical concept and features of the present invention and are intended to enable those skilled in the art to understand the content of the present invention and implement the same, and are not intended to limit the scope of the present invention. All equivalent changes or modifications made in accordance with the spirit of the present invention should be construed to be included in the scope of the present invention.
Claims (9)
1. A process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole comprising the steps of:
(a) Reacting the compound I in the solvent with hydroxylamine salt under the action of an alkaline catalyst to obtain an organic solvent mixture containing the compound III; the compound I is 3-methyl-2-butenal, and the compound III is 3-methyl-2-butenal oxime;
(b) And (3) carrying out cyclization reaction on the compound III under the condition of an acid catalyst to obtain the 5, 5-dimethyl-4, 5-dihydro isoxazole.
2. A process for the preparation of 5, 5-dimethyl-4, 5-dihydroisoxazole according to claim 1, characterized in that: in the step (a), the alkaline catalyst is a mixture of one or more selected from sodium hydroxide, potassium hydroxide and ammonia.
3. A process for the preparation of 5, 5-dimethyl-4, 5-dihydroisoxazole according to claim 1 or 2, characterized in that: in the step (a), the solvent is a mixture composed of one or more selected from water, acetonitrile, toluene, xylene and dichloromethane;
preferably, the solvent is acetonitrile.
4. A process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole according to claim 3, characterized in that: in step (a), the molar ratio of the compound I to the hydroxylamine salt is 1:1 to 1.5;
the temperature of the reaction is 10 ℃ to 70 ℃,
preferably, the reaction temperature of the cyclization reaction is 10-30 ℃;
the reaction time is 1 h-24 h.
5. A process for the preparation of 5, 5-dimethyl-4, 5-dihydroisoxazole according to claim 1, characterized in that: in step (a), the mass ratio of the basic catalyst to the hydroxylamine salt is about 1 to 1.2:1.1.
6. a process for the preparation of 5, 5-dimethyl-4, 5-dihydroisoxazole according to claim 1, characterized in that: in the step (b), the acid catalyst is a mixture of one or more selected from heteropolyacid, phosphotungstic acid, molybdenum phosphoric acid and maleic acid.
7. A process for the preparation of 5, 5-dimethyl-4, 5-dihydroisoxazole according to claim 1 or 6, characterized in that: in step (b), the molar amount of the acid catalyst is 10 to 100% of the molar amount of the compound I.
8. The process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole according to claim 7, wherein: step (b), the reaction temperature of the cyclization reaction is 20-80 ℃;
preferably, the reaction temperature of the cyclization reaction is 20-30 ℃.
9. The process for preparing 5, 5-dimethyl-4, 5-dihydroisoxazole according to claim 7, wherein: step (b), wherein the reaction time of the cyclization reaction is 1-48 h
Preferably, the reaction time of the cyclization reaction is 36-48 hours.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN117285479A (en) * | 2023-09-26 | 2023-12-26 | 山东滨农科技有限公司 | Preparation method of 3-chloro-5, 5-dimethyl-4, 5-dihydro-isoxazole |
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| CN102666503A (en) * | 2009-11-26 | 2012-09-12 | 巴斯夫欧洲公司 | Method for producing 5,5-disubstituted 2-isoxazolines |
| CN111491926A (en) * | 2017-12-15 | 2020-08-04 | 组合化学工业株式会社 | Novel method for producing 5, 5-disubstituted-4, 5-dihydroisoxazoles |
| CN112004805A (en) * | 2018-04-27 | 2020-11-27 | 组合化学工业株式会社 | Process for producing 5, 5-disubstituted-4, 5-dihydroisoxazoles |
| CN112358454A (en) * | 2020-09-30 | 2021-02-12 | 山东润博生物科技有限公司 | Preparation method of 4, 5-dihydroisoxazole derivative |
| CN114644602A (en) * | 2020-12-17 | 2022-06-21 | 帕潘纳(北京)科技有限公司 | Preparation method of dihydro isoxazole compound |
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| CN117285479A (en) * | 2023-09-26 | 2023-12-26 | 山东滨农科技有限公司 | Preparation method of 3-chloro-5, 5-dimethyl-4, 5-dihydro-isoxazole |
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