CN103951632B - The preparation method of 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds - Google Patents
The preparation method of 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds Download PDFInfo
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- NTFHNBWMARSIJQ-UHFFFAOYSA-N Oc1c(C(C2)C2C(C(CF)(F)Br)=O)ccc(F)c1 Chemical compound Oc1c(C(C2)C2C(C(CF)(F)Br)=O)ccc(F)c1 NTFHNBWMARSIJQ-UHFFFAOYSA-N 0.000 description 1
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- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
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Abstract
The invention discloses a kind of 2,2, the fluoro-2H-1 of 7-tri-, the preparation method of 4-benzoxazine-3 (4H)-one compounds, the method comprises: fluoro-for 7-2H-1,4-benzoxazine-3 (4H)-one compounds and chlorination reagent are carried out chlorination reaction by (1) in the first reaction medium, generates 2, the chloro-7-of 2-bis-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds; (2) chloro-for 2,2-bis-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds and fluorination reagent are carried out chloro-fluorine permutoid reaction.Method provided by the invention can obtain higher product yield, due to use materials safety, be easy to get, also can not produce the intermediate product of potential safety hazard in reaction process, overcome the deficiency producing in expensive raw material price, poor stability and the reaction process existed in existing technique and have the intermediate product of potential safety hazard.
Description
Technical field
The present invention relates to the preparation method of 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds.
Background technology
WO2012/041789 describes 2-position and is had better weeding activity by the benzoxazinones of 1 or 2 halogen substiuted, especially 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds [formula (I)] has more excellent weeding activity.
WO2010/145992 describes the fluoro-2H-1 of preparation 2,2,7-tri-, the method of 4-benzoxazine-3 (4H)-one [formula (I-01)], wherein two, 2-position fluorine atom derives from bromo-2, the 2-ethyl difluoros of 2-[formula (V)], and its reaction process is as follows:
There is apparent shortcoming in above-mentioned preparation method: raw material 2-bromo-2, the price of 2-ethyl difluoro and 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene (DBU) is high, and yield is only 52%, cause the price of finished product very high, lack the market competitiveness; In addition, the easy moisture absorption of NaH and reaction process discharges hydrogen is dangerous high.
Based on above-mentioned shortcoming, what WO2013/092859 described a kind of improvement prepares the fluoro-6-amino-2H-1 of key intermediate 2,2,7-tri-, the method for 4-benzoxazine-3 (4H)-one, and its reaction process is as follows:
Although above-mentioned modification method avoids use 1 of costliness, 8-diazabicylo [5.4.0] 11 carbon-7-alkene (DBU) and dangerous material NaH, but still employ expensive raw material N, bromo-2,2-bis-monofluoroacetamides of N-dimethyl-2-[formula (VIII)]; Reaction process relates to dinitro compound [formula (X)], himself be heat-labile, in nitrifying process, have high risk.
Summary of the invention
The object of this invention is to provide a kind of 2,2, the fluoro-2H-1 of 7-tri-, the preparation method of 4-benzoxazine-3 (4H)-one compounds, the method overcome the fluoro-2H-1 of existing preparation 2,2,7-tri-, the expensive starting materials existed in the method for 4-benzoxazine-3 (4H)-one compounds and poor stability, the deficiency that product yield is lower.
The present inventor is through further investigation, be surprised to find that fluoro-for the 7-of cheapness 2H-1, the 2-position hydrogen atom of 4-benzoxazine-3 (4H)-one compounds carries out chlorination and can generate 2, the fluoro-2H-1 of the chloro-7-of 2-bis-, 4-benzoxazine-3 (4H)-one compounds, simultaneously 2, the fluoro-2H-1 of the chloro-7-of 2-bis-, two, the 2-position chlorine atom of 4-benzoxazine-3 (4H)-one compounds also can occur " chloro-fluorine permutoid reaction " smoothly, thus introduce two fluorine atoms in its 2-position, and then prepare 2, 2, the fluoro-2H-1 of 7-tri-, 4-benzoxazine-3 (4H)-one compounds, thus complete the present invention further.
To achieve these goals, the invention provides the preparation method of a kind of 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds, the method comprises the following steps:
(1) by the fluoro-2H-1 of 7-shown in formula (III), 4-benzoxazine-3 (4H)-one compounds and chlorination reagent carry out chlorination reaction in the first reaction medium, shown in production (II) 2, the chloro-7-of 2-bis-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds;
(2) 2,2-bis-chloro-7-fluoro-2H-1,4-benzoxazine-3 (4H) the-one compounds shown in formula (II) and fluorination reagent are carried out chloro-fluorine permutoid reaction;
Wherein,
R
1be selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 allyl group, C3-C6 halogenated allyl, C3-C6 propargyl, C3-C6 acetylenic halide propyl group, C1-C6 alkoxyl group, benzyl, methylsulfonyl and N, N-dialkyl group methylsulfonyl any one;
R
2be selected from hydrogen, nitro, amino, cyano group, isothiocyano, diazanyl and containing 1-3 nitrogen heterocycle in any one;
W is oxygen or sulphur.
The preparation method of described 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds provided by the invention can obtain higher product yield.
And, the materials safety used in method of the present invention, to be easy to get, also can not produce the intermediate product of potential safety hazard in reaction process, overcome the deficiency producing in expensive raw material price, poor stability and the reaction process existed in existing technique and have the intermediate product of potential safety hazard.
In addition, method of the present invention has evaded annulation complicated in prior art, and method technique is simpler, is easier to industrialization.
Other features and advantages of the present invention are described in detail in embodiment part subsequently.
Embodiment
Below the specific embodiment of the present invention is described in detail.Should be understood that, embodiment described herein, only for instruction and explanation of the present invention, is not limited to the present invention.
The invention provides the preparation method of 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds shown in a kind of formula (I), the method comprises the following steps:
(1) by the fluoro-2H-1 of 7-shown in formula (III), 4-benzoxazine-3 (4H)-one compounds and chlorination reagent carry out chlorination reaction in the first reaction medium, shown in production (II) 2, the chloro-7-of 2-bis-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds;
(2) 2,2-bis-chloro-7-fluoro-2H-1,4-benzoxazine-3 (4H) the-one compounds shown in formula (II) and fluorination reagent are carried out chloro-fluorine permutoid reaction;
Wherein,
R
1be selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 allyl group, C3-C6 halogenated allyl, C3-C6 propargyl, C3-C6 acetylenic halide propyl group, C1-C6 alkoxyl group, benzyl, methylsulfonyl and N, N-dialkyl group methylsulfonyl any one;
R
2be selected from hydrogen, nitro, amino, cyano group, isothiocyano, diazanyl and containing 1-3 nitrogen heterocycle in any one; The described heterocycle containing 1-3 nitrogen can be any one in pyrroles, pyrazoles, imidazoles, pyridine, pyrimidine, quinoline;
W is oxygen or sulphur.
In step (1), the usage quantity of described chlorination reagent is not particularly limited, and usually uses the chlorination reagent of reaction equivalent.The mol ratio of fluoro-2H-1, the 4-benzoxazine-3 (4H) of the 7-shown in described chlorination reagent and formula (III)-one compounds can be 1:(1-10), be preferably 1:(1-6).
In step (1), described chlorination reagent can be any chlorination reagent for chlorination reaction in this area.Described chlorination reagent can for being selected from least one in phosphorus pentachloride, phosphorus trichloride, chlorine, TCCA (Trichloroisocyanuric acid) and SULPHURYL CHLORIDE.Described chlorination reagent is preferably phosphorus pentachloride.Described phosphorus pentachloride can adopt the method for phosphorus trichloride and chlorine reaction in－situ to prepare.
In step (1), described first reaction medium is not particularly limited, and usually selects according to the solubleness situation of substrate.Described first reaction medium can for being selected from least one in hydrochloric ether, aromatic hydrocarbons, ester class, ethers and phosphorus trichloride.Described hydrochloric ether can for being selected from least one in methylene dichloride, ethylene dichloride, tetracol phenixin and zellon.Described aromatic hydrocarbons can for being selected from least one in toluene, dimethylbenzene and chlorobenzene.Described ester class can be butylacetate and/or isopropyl acetate.Described ethers can for being selected from least one in methyl tertiary butyl ether, tetrahydrofuran (THF) and methyltetrahydrofuran.
In step (1), described chlorination reaction can adopt the chlorination reaction condition of this area routine.Preferably, in order to improve selectivity and the transformation efficiency of reaction, described chlorination reaction condition is carried out under room temperature to reflux state.
In step (2), the consumption of described fluorination reagent is relevant with the fluorinated reactive of the fluorination reagent selected, as long as the consumption of described fluorination reagent can ensure that chloro-fluorine permutoid reaction is fully carried out.Preferably, the consumption of described fluorination reagent is 1 ~ 3 times of reaction equivalent.
In step (2), described fluorination reagent can be any fluorination reagent that chloromethyl on heterocycle can be converted into methyl fluoride in this area.Described fluorination reagent can be at least one in the complex compound of hydrogen fluoride, hydrogen fluoride tertiary amine salt and hydrogen fluoride and nitrogenous reagent.Described hydrogen fluoride tertiary amine salt can be hydrogen fluoride triethylamine salt and/or hydrogen fluoride tri-n-butylamine salt.The complex compound of described hydrogen fluoride and nitrogenous reagent can be pyridine hydrofluoride and/or pyrroles's hydrofluoride.Described fluorination reagent is preferably at least one in hydrogen fluoride triethylamine salt, hydrogen fluoride tri-n-butylamine salt and pyridine hydrofluoride.
In step (2), described chloro-fluorine permutoid reaction existence second reaction medium or there is not the second reaction medium environment in carry out.Described second reaction medium is not particularly limited, and usually selects according to the solubleness situation of substrate, as long as fully can dissolve substrate, reaction is carried out smoothly.Described second reaction medium can be at least one in hydrochloric ether, aromatic hydrocarbons, ester class and ethers.Described hydrochloric ether can for being selected from least one in methylene dichloride, ethylene dichloride, tetracol phenixin and zellon.Described aromatic hydrocarbons can for being selected from least one in toluene, dimethylbenzene and chlorobenzene.Described ester class can be butylacetate and/or isopropyl acetate.Described ethers can for being selected from least one in methyl tertiary butyl ether, tetrahydrofuran (THF) and methyltetrahydrofuran.
In step (2), the temperature of reaction of described chloro-fluorine permutoid reaction is relevant to the fluorinated reactive of the fluorination reagent selected.Such as, when the pyridine hydrofluoride selecting fluorinated reactive higher, reaction can be carried out under room temperature or lower temperature.
According to the present invention, compound shown in formula (II) can be any one compound following:
The chloro-7-of 2,2-bis-fluoro-2H-1,4-benzoxazine-3 (4H)-one,
2,2-bis-chloro-6-nitro-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one,
2,2-bis-chloro-6-amino-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one,
2,2-bis-chloro-6-isocyano--7-fluoro-2H-1,4-benzoxazine-3 (4H)-one,
2,2-bis-chloro-6-diazanyl-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one,
2,2-bis-chloro-4-propargyl-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one,
2,2-bis-chloro-4-propargyl-6-nitro-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one,
2,2-bis-chloro-4-propargyl-6-amino-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one,
2,2-bis-chloro-4-propargyl-6-isocyano--7-fluoro-2H-1,4-benzoxazine-3 (4H)-one and
2,2-bis-chloro-4-propargyl-6-diazanyl-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one.
In described reaction, fluoro-2H-1, the 4-benzoxazine-3 (4H) of the 7-shown in formula (III)-one compounds according to the ordinary method synthesis of this area or can be purchased (Jiangsu Tian Shi Fine Chemical Co., Ltd, article No.: 579-56) acquisition.
According to the present invention, the step (1) in the preparation method of shown in described formula (I) 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds and step (2) two-step reaction can in introducing substituent R
1and R
2before or after carry out.
Below will be described the present invention by specific embodiment.
In following examples, the calculation formula of the yield of 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds is as follows:
Yield=(mole number of mole number/7-fluoro-2H-1,4-benzoxazine-3 (4H)-one of 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds) × 100%
Embodiment 1
The present embodiment is in order to illustrate the preparation method of 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one.
(1) in phosphorus trichloride (42g) suspension liquid of fluoro-2H-1, the 4-benzoxazine-3 (4H)-one (8.36g, 49mmol) of 7-, chlorine (7.23g, 102mmol) is passed under room temperature; Then phosphorus trichloride is reclaimed in air distillation, obtain 11.32g reddish-brown liquid, GC/MSm/e (M+)=234.96, show that this liquid comprises 99% 2, the chloro-7-of 2-bis-fluoro-2H-1,4-benzoxazine-3 (4H)-one (structure is shown below).
The reddish-brown that takes a morsel liquid, adds tetracol phenixin in this reddish-brown liquid, cooling, leave standstill, crystallize out is used for NMR(nucleus magnetic resonance) test, NMR result is: 1H-NMR (500MHz, DMSO-d6): δ (ppm)=2.90 (br, 1H).
(2) the reddish-brown fluid drips that step (1) obtains is added in pyridine hydrofluoride (27.92g, 100mmol) solution, then stirs 4 hours at 50 DEG C, be extracted with ethyl acetate (extract three times, use 30mL ethyl acetate at every turn); Merge organic phase, being washed to pH with the 5%NaOH aqueous solution is 5, sloughs ethyl acetate, obtains 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one (8.63g, 41.6mmol), yield 84.97%.
Get appropriate 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one and carry out gas chromatography-mass spectrum (GC/MS) analysis and NMR analysis, result is as follows:
GC/MSm/e(M+)=203.02；
1H-NMR(500MHz,CDCl
3):δ(ppm)=2.90(br,1H)。
Embodiment 2
The present embodiment is in order to illustrate the fluoro-6-nitro of 2,2,7-tri--2H-1, the preparation method of 4-benzoxazine-3 (4H)-one.
(1) in phosphorus trichloride (42g) suspension liquid of fluoro-2H-1, the 4-benzoxazine-3 (4H)-one (10.61g, 49mmol) of 6-nitro-7-, chlorine (7.23g, 102mmol) is passed under room temperature; Then phosphorus trichloride is reclaimed in air distillation, obtain 13.21g reddish-brown liquid, GC/MSm/e (M+)=279.95, show that this liquid comprises 99% 2,2-bis-chloro-6-nitro-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one (structure is shown below).
The reddish-brown that takes a morsel liquid, adds ethyl acetate in this reddish-brown liquid, cooling, leaves standstill, and crystallize out is used for NMR test, and NMR result is: 1H-NMR (500MHz, DMSO-d6): δ (ppm)=2.90 (br, 1H).
(2) the reddish-brown fluid drips that step (1) obtains is added in pyridine hydrofluoride (27.92g, 100mmol) solution, then stirs 2 hours, with dichloromethane extraction (extract three times, use 30mL methylene dichloride) at every turn at 20 DEG C; Merge organic phase, being washed to pH with the 5%NaOH aqueous solution is 6, sloughs methylene dichloride, obtains 2,2,7-tri-fluoro-6-nitro-2H-1 of brown solid, 4-benzoxazine-3 (4H)-one (10.42g, 41.16mmol), yield 83.99%.
Get appropriate 2,2,7-tri-fluoro-6-nitro-2H-1,4-benzoxazine-3 (4H)-one is carried out GC/MS and is analyzed and NMR analysis, and result is as follows:
GC/MSm/e(M+)=248.12；
1H-NMR(500MHz,CDCl
3):δ(ppm)=2.90(br,1H),7.15(d,1H),7.80(d,1H)。
Embodiment 3
The present embodiment is in order to illustrate the fluoro-6-amino of 2,2,7-tri--2H-1, the preparation method of 4-benzoxazine-3 (4H)-one.
(1) in phosphorus trichloride (42g) suspension liquid of fluoro-2H-1, the 4-benzoxazine-3 (4H)-one (9.11g, 49mmol) of 6-amino-7-, chlorine (7.23g, 102mmol) is passed under room temperature; Then phosphorus trichloride is reclaimed in air distillation, obtain 11.55g reddish-brown liquid, GC/MSm/e (M+)=251.04, show that this liquid comprises 98% 2,2-bis-chloro-6-amino-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one (structure is shown below).
The reddish-brown that takes a morsel liquid, adds in ethyl acetate by this reddish-brown liquid, cooling, leaves standstill, and crystallize out is used for NMR test, and NMR result is: 1H-NMR (500MHz, DMSO-d6): δ (ppm)=2.90 (br, 1H).
(2) the reddish-brown fluid drips that step (1) obtains is added in pyridine hydrofluoride (27.92g, 100mmol) solution, then stirs 2 hours at 18 DEG C; Reaction solution is poured in the 5%NaOH aqueous solution, regulate pH to 8, filter 2,2, the 7-tri-fluoro-6-amino-2H-1 obtaining brown solid, 4-benzoxazine-3 (4H)-one (8.94g, 40.17mmol), yield 81.97%.
Get appropriate 2,2,7-tri-fluoro-6-amino-2H-1,4-benzoxazine-3 (4H)-one is carried out GC/MS and is analyzed and NMR analysis, and result is as follows:
GC/MSm/e(M+)=218.03；
1H-NMR(500MHz,DMSO-d
6):δ(ppm)=11.90(bs,1H),7.15(d,J=11.0Hz,1H),6.55(d,J=8.5Hz,1H),5.28(bs,2H)；13C-NMR(DMSO-d6,125MHz):δ(ppm)=153.7(t,J=38Hz);146.1(d,J=235Hz);133.9(d,J=15Hz);127.3(d,J=11Hz);120.9(d,J=3Hz);113.1(d,J=260Hz);140.9(d,J=24Hz);102.4(d,J=5Hz)。
Embodiment 4
The present embodiment is in order to illustrate the fluoro-4-propargyl of 2,2,7-tri--6-amino-2H-1, the preparation method of 4-benzoxazine-3 (4H)-one.
(1) in phosphorus trichloride (42g) suspension liquid of fluoro-2H-1, the 4-benzoxazine-3 (4H)-one (11.01g, 32.17mmol) of 4-propargyl-6-amino-7-, chlorine (7.23g, 102mmol) is passed under room temperature; Then phosphorus trichloride is reclaimed in air distillation, obtain 13.00g reddish-brown liquid, GC/MSm/e (M+)=287.99, show that this liquid comprises 98% 2,2-bis-chloro-4-propargyl-6-amino-7-fluoro-2H-1,4-benzoxazine-3 (4H)-one (structure is shown below).
The reddish-brown that takes a morsel liquid, will add in ethylene dichloride in this reddish-brown liquid, cooling, leave standstill, crystallize out is used for NMR test, and NMR result is: 1H-NMR (500MHz, DMSO-d6): δ (ppm)=2.90 (br, 1H).
(2) the reddish-brown fluid drips that step (1) obtains is added in pyridine hydrofluoride (27.92g, 100mmol) solution, then stirs 2 hours at 20 DEG C; Be extracted with ethyl acetate (extract three times, use 30mL ethyl acetate at every turn); Merge organic phase, being washed to pH with the 5%NaOH aqueous solution is 7, sloughs ethyl acetate, obtains the fluoro-4-propargyl of 2,2,7-tri--6-amino-2H-1,4-benzoxazine-3 (4H)-one (6.87g, 25.74mmol), yield 80%.Used recrystallizing methanol, obtained faint yellow to white crystal, fusing point: 239.2 DEG C.
Get appropriate 2,2,7-tri-fluoro-4-propargyl-6-amino-2H-1,4-benzoxazine-3 (4H)-one is carried out liquid chromatography-mass spectrography (LC/MS) and is analyzed and NMR analysis, and result is as follows:
LC/MSm/e(M+)=256.05；
1H-NMR(500MHz,DMSO-d
6):δ(ppm)=3.45(s,1H),4.74(s,2H),5.42(s,2H),6.85(d,1H),7.26(d,1H)。
Embodiment 5
The present embodiment is in order to illustrate the preparation method of 2-(the fluoro-3-oxygen of 2,2,7-tri--4-propargyl-3,4-dihydro-2H-benzo [b] [Isosorbide-5-Nitrae] oxazines-6-base)-4,5,6,7-tetrahydrochysene-1H-isoindole-1,3 (2H)-diketone.
(1) under room temperature to 2-(the fluoro-3-oxygen of 7--4-propargyl-3,4-dihydro-2H-benzo [b] [1,4] oxazines-6-base)-4,5,6,7-tetrahydrochysene-1H-isoindole-1,3 (2H)-diketone (11.01g, chlorine (7.23g, 102mmol) is passed in phosphorus trichloride (42g) suspension liquid of 30.45mmol) (structure is such as formula 51 Suo Shi); Then phosphorus trichloride is reclaimed in air distillation, obtain 11.72g reddish-brown liquid, GC/MSm/e (M+)=287.99, shows 2-(the fluoro-3-oxygen-3 of the chloro-7-of 2,2-bis-that this liquid comprises 98%, 4-dihydro-2H-benzo [b] [1,4] oxazines-6-base)-4,5,6,7-tetrahydrochysene-1H-isoindole-1,3 (2H)-diketone (structure is such as formula 52 Suo Shi).
The reddish-brown that takes a morsel liquid, adds in ethyl acetate by this reddish-brown liquid, cooling, leaves standstill, and crystallize out is used for NMR test, and NMR result is: 1H-NMR (500MHz, DMSO-d6): δ (ppm)=2.90 (br, 1H).
(2) the reddish-brown fluid drips that step (1) obtains is added in pyridine hydrofluoride (27.92g, 100mmol) solution, then stirs 2 hours at 20 DEG C; Be extracted with ethyl acetate (extract three times, use 30mL ethyl acetate at every turn); Merge organic phase, being washed to pH with the 5%NaOH aqueous solution is 7, sloughs ethyl acetate, obtain 2-(the fluoro-3-oxygen of 2,2,7-tri--4-propargyl-3,4-dihydro-2H-benzo [b] [1,4] oxazines-6-base)-4,5,6,7-tetrahydrochysene-1H-isoindole-1,3 (2H)-diketone (9.7g, 24.36mmol), yield 80%.Used recrystallizing methanol, obtained white crystal, fusing point: 239.2 DEG C, boiling point: 605.8 ± 55 DEG C (760torr), density 1.57 ± 0.1g/cm
3.
Get appropriate 2,2,7-tri-fluoro-4-propargyl-6-amino-2H-1,4-benzoxazine-3 (4H)-one is carried out LC/MS and is analyzed and NMR analysis, and result is as follows:
LC/MSm/e(M+)=256.05；
1H-NMR(500MHz,DMSO-d
6):δ(ppm)=3.45(s,1H),4.74(s,2H),5.42(s,2H),6.85(d,1H),7.26(d,1H)。
Can find out that method according to the present invention can obtain higher product yield by the result of above-described embodiment.Simultaneously due to use in described method of the present invention materials safety, be easy to get, also can not produce the intermediate product of potential safety hazard in reaction process, overcome the deficiency producing in expensive raw material price, poor stability and the reaction process existed in existing technique and have the intermediate product of potential safety hazard.Described method of the present invention does not have complicated annulation, and therefore working method is simpler, is easier to industrialization.
More than describe the preferred embodiment of the present invention in detail; but the present invention is not limited to the detail in above-mentioned embodiment, within the scope of technical conceive of the present invention; can carry out multiple simple variant to technical scheme of the present invention, these simple variant all belong to protection scope of the present invention.
Claims (7)
1. the preparation method of shown in a formula (I) 2,2,7-tri-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds, it is characterized in that, the method comprises the following steps:
(1) by the fluoro-2H-1 of 7-shown in formula (III), 4-benzoxazine-3 (4H)-one compounds and chlorination reagent carry out chlorination reaction in the first reaction medium, shown in production (II) 2, the chloro-7-of 2-bis-fluoro-2H-1,4-benzoxazine-3 (4H)-one compounds;
(2) 2,2-bis-chloro-7-fluoro-2H-1,4-benzoxazine-3 (4H) the-one compounds shown in formula (II) and fluorination reagent are carried out chloro-fluorine permutoid reaction;
Wherein,
R
1be selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 allyl group, C3-C6 halogenated allyl, C3-C6 propargyl, C3-C6 acetylenic halide propyl group, C1-C6 alkoxyl group, benzyl, methylsulfonyl and N, N-dialkyl group methylsulfonyl any one;
R
2be selected from hydrogen, nitro, amino, cyano group, isothiocyano, diazanyl and containing 1-3 nitrogen heterocycle in any one;
W is oxygen or sulphur; Wherein,
In step (1), described chlorination reagent is selected from least one in phosphorus pentachloride, phosphorus trichloride, chlorine, TCCA (Trichloroisocyanuric acid) and SULPHURYL CHLORIDE;
In step (1), described first reaction medium is selected from least one in hydrochloric ether, aromatic hydrocarbons, ester class, ethers and phosphorus trichloride;
In step (2), described fluorination reagent is at least one in the complex compound of hydrogen fluoride, hydrogen fluoride tertiary amine salt and hydrogen fluoride and nitrogenous reagent.
2. method according to claim 1, wherein, in step (1), the mol ratio of fluoro-2H-1, the 4-benzoxazine-3 (4H) of the 7-shown in described chlorination reagent and formula (III)-one compounds is 1:(1-10).
3. method according to claim 2, wherein, in step (1), the mol ratio of fluoro-2H-1, the 4-benzoxazine-3 (4H) of the 7-shown in described chlorination reagent and formula (III)-one compounds is 1:(1-6).
4. method according to claim 1, wherein, in step (1), described chlorination reaction is carried out under room temperature to reflux state.
5. method according to claim 1, wherein, in step (2), the consumption of described fluorination reagent is 1 ~ 3 times of reaction equivalent.
6. method according to claim 1, wherein, described hydrogen fluoride tertiary amine salt is hydrogen fluoride triethylamine salt and/or hydrogen fluoride tri-n-butylamine salt, and the complex compound of described hydrogen fluoride and nitrogenous reagent is pyridine hydrofluoride and/or pyrroles's hydrofluoride.
7. method according to claim 1, wherein, chloro-fluorine permutoid reaction described in step (2) existence second reaction medium or there is not the second reaction medium environment in carry out, described second reaction medium is at least one in hydrochloric ether, aromatic hydrocarbons, ester class and ethers.
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| WO2011018486A2 (en) * | 2009-08-14 | 2011-02-17 | Basf Se | Herbicidally active composition comprising benzoxazinones |
| CN103221409A (en) * | 2010-10-01 | 2013-07-24 | 巴斯夫欧洲公司 | Herbicidal benzoxazinones |
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