CN104876920A - Isooxazole compounds and intermediates thereof, and preparation method and application thereof - Google Patents
Isooxazole compounds and intermediates thereof, and preparation method and application thereof Download PDFInfo
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- CN104876920A CN104876920A CN201510228197.9A CN201510228197A CN104876920A CN 104876920 A CN104876920 A CN 104876920A CN 201510228197 A CN201510228197 A CN 201510228197A CN 104876920 A CN104876920 A CN 104876920A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
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- 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
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention relates to isooxazole compounds [2-(4,5-dihydroisooxazolyl-3-yl)-3-methyl-4-(methylsulfonyl)phenyl]-(5-hydroxy-1-methyl-1H-pyrazolyl-4-yl)ketone of which the structural formula is disclosed in the specification. The invention also relates to intermediates 3-[6-bromo-2-methyl-3-methylsulfonylphenyl]-4,5-dihydroisooxazole and 3-methylsulfonyl-2-methyl-6-bromobenzaldehyde and a preparation method of the compounds. The test detects that the isooxazole compounds have certain preventive effects on piemarker, and can be used as a weedicide.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of isoxazole compounds, intermediate, preparation method and the application as weedicide thereof.
Background technology
Isoxazole is a kind of heterogeneous ring compound, and it has special physiology and pharmacologically active, as antibacterial, spasmolytic, anti-inflammatory, coordinate plant growth and anti-platelet aggregation etc.Be used as calcium as medicine ， isoxazole compound regulate and be used for the treatment of alzheimer's disease, some isoxazole compounds can also kill microorganism.Some isoxazole compounds are also had to be used as weedicide.In addition, excellent photoelectric characteristic and the transmittability of current carrier isoxazole compound make it be widely used in photoelectric functional material and organic photoconductor.
Summary of the invention
The object of the invention is to provide a kind of isoxazole compounds, intermediate and its preparation method and application.
For achieving the above object, the present invention adopts following technical scheme:
A kind of isoxazole compounds [2-(4; 5-dihydro-isoxazole-3-base)-3-methyl-4-(p-dimethylamino-azo-benzene acyl group) phenyl]-(5-hydroxyl-1-methyl isophthalic acid H-pyrazoles-4-base) ketone (being designated as compound 1), its structural formula is as follows:
。
A kind of intermediate 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles (being designated as compound 2) of above-mentioned isoxazole compounds, its structural formula is as follows:
。
A kind of intermediate 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde (being designated as compound 3) of above-claimed cpd, its structural formula is as follows:
。
A preparation method for above-mentioned isoxazole compounds, it comprises the steps:
1) with 4-methyl sulphonyl-2,3-dimethyl bromobenzene for raw material, at CCl
4diisopropyl azodicarboxylate and N-bromo-succinimide is added in solvent, then illumination backflow 3-6h under incandescent light, filtered while hot, filtrate decompression evaporate to dryness, residual solid silica gel column chromatography is separated, and obtains 4-methyl sulphonyl-2-methyl-3-brooethyl bromobenzene and 4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene;
2) with the 4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene in step 1) products therefrom for raw material, acetonitrile is solvent, drips N-methylmorpholine-N-oxide water solution (50
wt%), stirring reaction 6-24h, to proceed in water and is 3-4 with concentrated hydrochloric acid (concentration of commercially available concentrated hydrochloric acid is 37%) tune pH, and hold over night (12h) separates out solid, filtration, and gained solid is above-mentioned intermediate 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde;
3) with step 2) products therefrom 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde is raw material, methyl alcohol is solvent, add oxammonium hydrochloride, back flow reaction 1-4h, remove methyl alcohol under reduced pressure, solid saturated common salt water washing, and vacuum-drying, obtain solid 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde oxime;
4) step 3) products therefrom 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde oxime is scattered in methylene dichloride, pass into ethene 15-45min at ambient temperature, then chlorine bleach liquor's (available chlorine content is not less than 10%) is added, and in ethene atmosphere stirring reaction 12-24h, stratification, organic phase through washing, dry, remove methylene dichloride under reduced pressure, obtain above-mentioned intermediate 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles;
5) in pressurized vessel, add step 4) products therefrom 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazole and Rong Ji diox, and add 1-methyl-5-hydroxypyrazoles hydrochloride, calcium hydroxide, triphenylphosphine and Palladous chloride (II) under agitation, after pressurized vessel rinses with CO, CO pressure is increased to 1-2MPa, pressurized vessel is heated to 120-140 DEG C, then CO pressure is increased to 2-4MPa, and at 120-140 DEG C, stirring reaction 18-30h under 2-4MPa pressure; Water is added in the reactive mixture after reaction terminates; the undissolved material of filtering also steams Chu diox and water; precipitated product; be cooled to room temperature and filter, wash gained solid; be aforesaid compound [2-(4,5-dihydro-isoxazole-3-base)-3-methyl-4-(p-dimethylamino-azo-benzene acyl group) phenyl]-(5-hydroxyl-1-methyl isophthalic acid H-pyrazoles-4-base) ketone.
Concrete, in step 1), every 1g 4-methyl sulphonyl-2,3-dimethyl bromobenzene adds 2-4mL tetracol phenixin, 0.02-0.06g Diisopropyl azodicarboxylate, 0.65-0.75g N-bromo-succinimide.The leacheate that in step 1), silica gel column chromatography is used is that the ethyl acetate of 1:4-6 and sherwood oil form by volume ratio.
Step 2) in, every 1g 4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene adds 7-10mL acetonitrile, the N-methylmorpholine-N-oxide water solution of 1.5-3mL massfraction 50%, 25-50mL water.
In step 3), every 1g 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde adds 10-20mL methyl alcohol, 0.2-0.25g oxammonium hydrochloride.
In step 4), every 1g 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde oxime adds 8-15mL methylene dichloride, 1.5-5mL chlorine bleach liquor.
In step 5), the mol ratio of 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles, 1-methyl-5-hydroxypyrazoles hydrochloride, calcium hydroxide, triphenylphosphine and Palladous chloride (II) is: 1:1-1.2:1.1-1.3:0.03-0.04:0.01-0.013.
Synthetic route in the present invention is as follows:
。
Wherein, get 0.5g step 2) products therefrom is dissolved in 20mL methyl alcohol, and at room temperature leave standstill 5-7 days, the monocrystalline of 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde can be obtained.Getting 0.5g step 4) products therefrom is dissolved in 20mL methyl alcohol, at room temperature leaves standstill 5-7 days, can obtain the monocrystalline of 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles.
Compared to the prior art, beneficial effect of the present invention:
Present invention finds a kind of novel isoxazole compounds [2-(4,5-dihydro-isoxazole-3-base)-3-methyl-4-(p-dimethylamino-azo-benzene acyl group) phenyl]-(5-hydroxyl-1-methyl isophthalic acid H-pyrazoles-4-base) ketone (compound
1) and intermediate 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazole (compounds
2), 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde (compound
3), and give the preparation method of above-claimed cpd.Preparation method is with 4-methyl sulphonyl-2,3-dimethyl bromobenzene for raw material, passes through with the bromo-reaction of N-succimide and obtains compound with the oxidizing reaction of N-methylmorpholine-N-oxide compound
3, then obtain compound by compound 3 through condensation and cyclization
2, compound 2 is obtained by reacting compound with 5-methyl isophthalic acid-hydroxypyrazoles and CO again
1, this synthetic method mild condition, product yield is higher.In addition, through test, the present invention finds that: isoxazole compounds has certain preventive effect to piemarker, have the potential being used as weedicide.
Accompanying drawing explanation
The molecular structure that the X-ray single crystal diffraction that Fig. 1 shows crystal 1 obtains;
The molecule space that the X-ray single crystal diffraction that Fig. 2 shows crystal 1 obtains piles up figure;
The molecular structure that the X-ray single crystal diffraction that Fig. 3 shows crystal 2 obtains;
The molecule space that the X-ray single crystal diffraction that Fig. 4 shows crystal 2 obtains piles up figure; Fusing point measures in the scope of 100 DEG C to 200 DEG C by using numeral melting point instrument, and heating rate is 3 DEG C/min, and sample size is 5-10mg.
Embodiment
Do to introduce in detail further to technical scheme of the present invention below in conjunction with embodiment, but protection scope of the present invention is not limited thereto.
Instrument title used in following embodiment and model: BRUKER AVANCE400 type nuclear magnetic resonance analyser; Agilent 1100 LC-MS mass spectrograph; X-ray, German Apex II type X-ray single crystal diffraction instrument; AVATAR360 type Fourier transformation infrared spectrometer (KBr compressing tablet)
embodiment 1
Preparation 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde (compound
3)
4g 4-methyl sulphonyl-2,3-dimethyl bromobenzene, 10mL tetracol phenixin, 0.16g Diisopropyl azodicarboxylate and 2.72g N-bromo-succinimide is added, illumination backflow 5h under incandescent light, filtered while hot, filtrate decompression evaporate to dryness in 50mL reactor.Residual solid silica gel column chromatography (developping agent is ethyl acetate, the sherwood oil mixed solution of volume ratio 1:5) is separated, and obtains 4-methyl sulphonyl-2-methyl-3-brooethyl bromobenzene and 4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene.
4-methyl sulphonyl-2-methyl-3-brooethyl bromobenzene, white powder, fusing point: 99.3-100.1 DEG C, productive rate: 56.5%.MS (M+H
+)：341.1，IR
ν: 3084(Ar-CH
3) 3012(Ar-H) 2920(SO
2-CH
3) 1303 1126(-SO
2-)；
1H NMR (400 MHz, CDCl
3,)
δ: 7.85 (d,
J= 8.6 Hz, 1H, Ar-H), 7.75 (d,
J= 8.6 Hz, 1H, Ar-H), 4.91 (s, 2H, -CH
2Br), 3.28 (s, 3H, SO
2-CH
3), 2.62 (s, 3H, Ar-CH
3)。
4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene, white powder, fusing point: 157.6-158.1 DEG C, productive rate: 34.5%.MS (M+H
+): 341.1；IR
ν:3081(Ar-CH
3), 3007(Ar-H), 2917(, SO
2-CH
3), 1303 1126(-SO
2-)；
1H NMR (400 MHz, CDCl
3)
δ: 7.92 (d,
J= 8.6 Hz, 1H, Ar-H), 7.67 (d,
J= 8.6 Hz, 1H, Ar-H), 4.74 (s, 2H, -CH
2Br), 3.12 (s, 3H, SO
2-CH
3), 2.86 (s, 3H, Ar-CH
3)。
In 50mL reactor, add 4g 4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene and 30mL acetonitrile, stirred at ambient temperature dissolves, and instills 8mL concentration 50 in 30 minutes
wtn-methylmorpholine-N-the oxide water solution of %, stirring reaction 12h.Pour in 200mL water, adjust about pH to 3.5 with concentrated hydrochloric acid, hold over night (12h) separates out solid, and filter, the solid of gained is 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde.This solid is white powder, fusing point: 122.7-124.1 DEG C, productive rate: 79.1%.
1h NMR confirms compound
3existence.MS(M+H
+) 276.9; IR
ν:3074(Ar-CH
3), 3014(Ar-H), 2932(SO
2-CH
3), 1705(C=O), 1305 1121(-SO
2-);
1H NMR (400 MHz, CDCl
3)
δ: 10.49 (s, 1H, -CHO), 8.13 (d,
J= 8.6 Hz, 1H, Ar-H), 7.73 (d,
J= 8.6 Hz, 1H, Ar-H), 3.13 (s, 3H, SO
2-CH
3), 2.90 (s, 3H, Ar-CH
3).
Get the above-mentioned gained dissolution of solid of 0.5g in 20mL methyl alcohol; at room temperature leave standstill; obtain the monocrystalline (being designated as crystal 1) of 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde after 7 days, confirm the existence of crystalline form 1 through X-ray single crystal diffraction, crystalline structure is as attached Fig. 1 and 2.The research of crystal 1 is shown: the underlying crystal structure of this crystal is oblique system.Structure cell has spacer P2 (1)/c.The crystal structure characteristic data (measuring at 20 DEG C) of crystal 1, refer to following table 1.In table 1, a, b, c=structure cell length of side; α, β, γ=structure cell angle; Molecule number in Z=structure cell.
embodiment 2
Preparation 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazole (compounds
2)
Get 4g 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde to be dissolved in 60mL methyl alcohol, add 0.84g oxammonium hydrochloride, backflow 2h.Remove methyl alcohol under reduced pressure, solid saturated common salt water washing, and vacuum-drying, obtain solid 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde oxime.White powder, productive rate: 96.9%.MS(M+H
+) 292.2; IR
ν: 3078(Ar-CH
3), 3006(Ar-H), 2930(SO
2-CH
3), 1558(C=N), 1305 1123(-SO
2-);
1H NMR (400 MHz, DMSO)
δ: 11.55 (s, 1H, -NOH), 8.03 (d,
J= 8.4 Hz, 2H, Ar-H), 7.86 (s, 1H,-CH=N-), 7.68 (d,
J= 8.4 Hz, 1H, Ar-H), 3.28 (s, 3H, SO
2-CH
3), 2.68 (s, 3H, Ar-CH
3).
Getting 2g 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde oxime is scattered in 20mL methylene dichloride, at room temperature passes into ethene 30 min, adds 5mL chlorine bleach liquor (available chlorine content is not less than 10%), then in ethene atmosphere, stir 12h, stratification.Organic phase is through washing, and anhydrous sodium sulfate drying, removes dichloromethane solvent under reduced pressure, and obtain white solid 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles, its fusing point is 160.8-161.7 DEG C, productive rate: 76.9%.
1h NMR confirms the existence of compound 2.MS (M+H
+) 318.1;
1H NMR (400 MHz, CDCl
3)
δ: 8.01 (d,
J= 8.6 Hz, 1H, Ar-H), 7.70 (d,
J= 8.6 Hz, 1H, Ar-H), 4.61 (t,
J= 10.1 Hz, 2H, -CH
2-), 3.29 (t,
J= 10.1 Hz, 2H, -CH
2-), 3.11 (s, 3H, SO
2-CH
3), 2.69 (s, 3H, Ar-CH
3).
Getting the above-mentioned gained solid of 0.5g is dissolved in 20mL methyl alcohol, at room temperature leave standstill, after 7 days, obtain the monocrystalline (being designated as crystal 2) of 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles, confirm the existence of crystalline form 2 through X-ray single crystal diffraction, crystalline structure is as accompanying drawing 3 and 4.The research of crystal 2 is shown: the underlying crystal structure of this crystal is triclinic(crystalline)system.Structure cell has spacer P-1.The crystal structure characteristic data (measuring at 20 DEG C) of crystal 2, refer to following table 2.In table 2, a, b, c=structure cell length of side; α, β, γ=structure cell angle; Molecule number in Z=structure cell.
embodiment 3
Preparation [2-(4,5-dihydro-isoxazole-3-base)-3-methyl-4-(p-dimethylamino-azo-benzene acyl group) phenyl]-(5-hydroxyl-1-methyl isophthalic acid H-pyrazoles-4-base) ketone (compound
1)
By 3.18g 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4 in pressurized vessel, 5-dihydro-isoxazole is dissolved in 400mL diox, and under agitation adds 1.34g 1-methyl-5-hydroxypyrazoles hydrochloride, 0.8g calcium hydroxide, 84mg triphenylphosphine and 21mg Palladous chloride (II).Pressurized vessel CO rinses 3 times, and CO pressure is increased to 2MPa, and pressurized vessel is heated to 130 DEG C, then CO pressure is increased to 3MPa.And at 130 DEG C, stirring reaction 24h under 3MPa pressure.Reaction terminates to add about 100g water in backward reaction mixture, and the undissolved material of filtering also steams Chu diox and water, obtains the final volume of about 50mL.Add about 50mL methyl alcohol and 25mL concentrated hydrochloric acid precipitated product under 60 DEG C of conditions wherein.Be cooled to room temperature and filter, wash gained solid; obtain aforesaid compound [2-(4,5-dihydro-isoxazole-3-base)-3-methyl-4-(p-dimethylamino-azo-benzene acyl group) phenyl]-(5-hydroxyl-1-methyl isophthalic acid H-pyrazoles-4-base) ketone.
1h NMR confirms the existence of compound 1, productive rate 73.9%.
1H NMR (400 MHz, CDCl
3)
δ: 8.01 (d,
J = 8.6 Hz, 1H), 7.70 (d,
J= 8.6 Hz, 1H), 7.37 (s, 1H), 4.61 (t,
J = 10.1 Hz, 2H), 3.74 (s, 3H), 3.41 (s, 1H), 3.29 (t,
J = 10.1 Hz, 2H), 3.11 (s, 3H), 2.69 (s, 3H).。
Application test: the weeding activity greenhouse test of the compounds of this invention 1:
What quantitative gramineous weeds (barnyard grass, lady's-grass) and broadleaf weeds (youth-and-old-age, piemarker) seed are sowed at respectively diameter 7cm is equipped with in the dixie cup of Nutrition Soil, after planting earthing 1cm, in hot-house culture after suppression, trickle, seedling pre-treatment was carried out at after planting 24 hours; Seedling aftertreatment need emerge after thinning, field planting (gramineous weeds 10-20 strain/cup, broadleaf weeds 2-4 strain/cup), treat the gramineous weeds 1.5-2 leaf phase, broadleaf weeds 2 leaf periods, carry out spraying process by 1000 g of compound 1/ hectare track type as composition spray.Repeat for three times.After liquid natural air drying, be placed in greenhouse and manage according to a conventional method, the situation of growing of routine observation weeds, and according to practical situation, periodical visual inspection investigation medicament is to the preventive effect of weeds after process.
Effect grade scale, 0 is invalid, and 100% for kill weeds completely.
After seedling, test result is as follows:
During 1000 grams/ha of consumptions, the preventive effect of compound 1 pair of piemarker is 10%.
Above-described embodiment is for illustration of the present invention and should not be construed as restriction the present invention, those skilled in the art is to be understood that: still can modify to the present invention or replace on an equal basis, and not departing from any modification or partial replacement of the spirit and scope of the present invention, it all should be encompassed in the middle of right of the present invention.
Claims (10)
1. an isoxazole compounds, its structural formula is as follows:
。
2. an intermediate for isoxazole compounds described in claim 1, its structural formula is as follows:
。
3. an intermediate for compound described in claim 2, its structural formula is as follows:
。
4. a preparation method for isoxazole compounds described in claim 1, is characterized in that, comprises the steps:
1) with 4-methyl sulphonyl-2,3-dimethyl bromobenzene for raw material, at CCl
4in add Diisopropyl azodicarboxylate and N-bromo-succinimide, then illumination backflow 3-6h under incandescent light, filtered while hot, filtrate decompression evaporate to dryness, residual solid silica gel column chromatography is separated, and obtains 4-methyl sulphonyl-2-methyl-3-brooethyl bromobenzene and 4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene;
2) with the 4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene in step 1) products therefrom for raw material, acetonitrile is solvent, drip N-methylmorpholine-N-oxide water solution, stirring reaction 6-24h, to proceed in water and to adjust pH to be 3-4 with concentrated hydrochloric acid, hold over night separates out solid, and filter, gained solid is intermediate 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde according to claim 3;
3) with step 2) products therefrom 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde is raw material, methyl alcohol is solvent, add oxammonium hydrochloride, back flow reaction 1-4h, remove methyl alcohol under reduced pressure, solid saturated common salt water washing, and vacuum-drying, obtain solid 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde oxime;
4) step 3) products therefrom 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde oxime is scattered in methylene dichloride, pass into ethene 20-45min at ambient temperature, then chlorine bleach liquor is added, and in ethene atmosphere stirring reaction 12-24h, stratification, organic phase through washing, dry, remove methylene dichloride under reduced pressure, obtain intermediate 3-according to claim 2 [the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles;
5) in pressurized vessel, add step 4) products therefrom 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazole and Rong Ji diox, and add 1-methyl-5-hydroxypyrazoles hydrochloride, calcium hydroxide, triphenylphosphine and Palladous chloride under agitation, after pressurized vessel rinses with CO, CO pressure is increased to 1-2MPa, pressurized vessel is heated to 120-140 DEG C, then CO pressure is increased to 2-4MPa, and at 120-140 DEG C, stirring reaction 18-30h under 2-4MPa pressure; Add water in the reactive mixture after reaction terminates, the undissolved material of filtering also steams Chu diox and water, precipitated product, is cooled to room temperature and filters, washes gained solid, being compound described in claim 1.
5. preparation method as claimed in claim 4, is characterized in that: in step 1), and every 1g 4-methyl sulphonyl-2,3-dimethyl bromobenzene adds 2-4mL tetracol phenixin, 0.02-0.06g Diisopropyl azodicarboxylate, 0.65-0.75g N-bromo-succinimide.
6. preparation method as claimed in claim 4; it is characterized in that: step 2) in, every 1g 4-methyl sulphonyl-3-methyl-2-brooethyl bromobenzene adds 7-10mL acetonitrile, the N-methylmorpholine-N-oxide water solution of 1.5-3mL massfraction 50%, 25-50mL water.
7. preparation method as claimed in claim 4, is characterized in that: in step 3), and every 1g 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde adds 10-20mL methyl alcohol, 0.2-0.25g oxammonium hydrochloride; In step 4), every 1g 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde oxime adds 8-15mL methylene dichloride, 1.5-5mL chlorine bleach liquor.
8. preparation method as claimed in claim 4, it is characterized in that: in step 5), the mol ratio of 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles, 1-methyl-5-hydroxypyrazoles hydrochloride, calcium hydroxide, triphenylphosphine and Palladous chloride is: 1:1-1.2:1.1-1.3:0.03-0.04:0.01-0.013.
9. preparation method as claimed in claim 4, is characterized in that: get 0.5g step 2) products therefrom is dissolved in 20mL methyl alcohol, and at room temperature leave standstill 5-7 days, obtain the monocrystalline of 3-methyl sulphonyl-2-methyl-6-bromobenzaldehyde; Getting 0.5g step 4) products therefrom is dissolved in 20mL methyl alcohol, at room temperature leaves standstill 5-7 days, obtains the monocrystalline of 3-[the bromo-2-methyl of 6--3-methylsulfonyl phenyl]-4,5-dihydro-isoxazoles.
10. isoxazole compounds described in claim 1 is as the application of weedicide.
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| CN (1) | CN104876920A (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105924405A (en) * | 2016-04-27 | 2016-09-07 | 广西师范大学 | Method for synthesizing isoxazole compound from nitrine and acetylenic ketone compound |
| CN107652246A (en) * | 2017-09-25 | 2018-02-02 | 江苏先导药业有限公司 | A kind of 3 [3 bromomethyls 6（Methyl sulphonyl）Phenyl] 4,5 2 Qingization isoxazoles preparation method |
| CN111440160A (en) * | 2020-04-26 | 2020-07-24 | 黑龙江省绥化农垦晨环生物制剂有限责任公司 | Preparation method and application of topramezone |
| CN112694425A (en) * | 2020-12-29 | 2021-04-23 | 利民化学有限责任公司 | Method for preparing topramezone intermediate by using supergravity reaction |
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| CN1248255A (en) * | 1997-01-17 | 2000-03-22 | 巴斯福股份公司 | 3-heterocyclyl-substituted benzoyl derivatives |
| CN1278259A (en) * | 1997-10-30 | 2000-12-27 | 日本曹达株式会社 | Novel benzoylpyrazole compound, production intermediate and herbicide |
| CN101687862A (en) * | 2007-07-06 | 2010-03-31 | 巴斯夫欧洲公司 | Crystalline form of [3-(4, 5-dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl) phenyl]-(5-hydroxy-1-methyl-1H-pyrazol-4-yl) methanone |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105924405A (en) * | 2016-04-27 | 2016-09-07 | 广西师范大学 | Method for synthesizing isoxazole compound from nitrine and acetylenic ketone compound |
| CN107652246A (en) * | 2017-09-25 | 2018-02-02 | 江苏先导药业有限公司 | A kind of 3 [3 bromomethyls 6（Methyl sulphonyl）Phenyl] 4,5 2 Qingization isoxazoles preparation method |
| CN111440160A (en) * | 2020-04-26 | 2020-07-24 | 黑龙江省绥化农垦晨环生物制剂有限责任公司 | Preparation method and application of topramezone |
| CN112694425A (en) * | 2020-12-29 | 2021-04-23 | 利民化学有限责任公司 | Method for preparing topramezone intermediate by using supergravity reaction |
| CN112694425B (en) * | 2020-12-29 | 2022-04-26 | 利民化学有限责任公司 | Method for preparing topramezone intermediate by using supergravity reaction |
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