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 PDF

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CN103951632B
CN103951632B CN201410141173.5A CN201410141173A CN103951632B CN 103951632 B CN103951632 B CN 103951632B CN 201410141173 A CN201410141173 A CN 201410141173A CN 103951632 B CN103951632 B CN 103951632B
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王文军
陈建伟
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Beijing Nutrichem Co Ltd
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    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • 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
    • 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
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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

Preparation method of 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound
Technical Field
The invention relates to a preparation method of 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compounds.
Background
WO2012/041789 describes that benzoxazinone compounds substituted by 1 or 2 halogens at the 2-position have better herbicidal activity, especially 2,2, 7-trifluoro-2H-1, 4-benzoxazin-3 (4H) -one compounds [ formula (I) ] have more excellent herbicidal activity.
WO2010/145992 describes a process for the preparation of 2,2, 7-trifluoro-2H-1, 4-benzoxazin-3 (4H) -one [ formula (I-01) ], wherein the two fluorine atoms in the 2-position are derived from ethyl 2-bromo-2, 2-difluoroacetate [ formula (V) ], which is carried out as follows:
the above preparation method has obvious disadvantages: the raw materials of 2-bromo-2, 2-difluoroacetic acid ethyl ester and 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) are high in price, the yield is only 52%, and the price of the final product is very high and the market competitiveness is poor; in addition, NaH is prone to moisture absorption and releases hydrogen during the reaction, which is highly dangerous.
Based on the above disadvantages, WO2013/092859 describes an improved process for preparing the key intermediate 2,2, 7-trifluoro-6-amino-2H-1, 4-benzoxazin-3 (4H) -one, the reaction procedure of which is as follows:
the improved process avoids the use of expensive 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) and hazardous material NaH, but still uses the expensive starting material N, N-dimethyl-2-bromo-2, 2-difluoroacetamide [ formula (VIII) ]; the reaction process involves a dinitro compound [ formula (X) ] which is itself thermally unstable and highly dangerous in the nitration process.
Disclosure of Invention
The invention aims to provide a preparation method of 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compounds, which overcomes the defects of expensive raw materials, poor safety and lower product yield existing in the existing preparation method of the 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compounds.
The inventor of the invention has conducted intensive research and unexpectedly found that chlorination of the hydrogen atom at the 2-position of a cheap 7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound can generate a 2, 2-dichloro-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound, and two chlorine atoms at the 2-position of the 2, 2-dichloro-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound can also smoothly generate chlorine-fluorine exchange reaction, so as to introduce two fluorine atoms at the 2-position of the compound, thereby preparing the 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -ones, and further completed the present invention.
In order to achieve the above objects, the present invention provides a method for preparing 2,2, 7-trifluoro-2H-1, 4-benzoxazin-3 (4H) -one compounds, comprising the steps of:
(1) carrying out chlorination reaction on 7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in formula (III) and a chlorination reagent in a first reaction medium to generate 2, 2-dichloro-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in formula (II);
(2) carrying out chlorine-fluorine exchange reaction on a 2, 2-dichloro-7-fluorine-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in a formula (II) and a fluorinating reagent;
wherein,
R1any one selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 allyl, C3-C6 haloalkyi, C3-C6 propargyl, C3-C6 halopropargyl, C1-C6 alkoxy, benzyl, methylsulfonyl and N, N-dialkylmethylsulfonyl;
R2any one selected from the group consisting of hydrogen, nitro, amino, cyano, isothiocyanato, hydrazino, and a heterocyclic ring containing 1 to 3 nitrogen atoms;
w is oxygen or sulfur.
The preparation method of the 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound provided by the invention can obtain higher product yield.
In addition, the raw materials used in the method are safe and easy to obtain, and no intermediate product with potential safety hazard is generated in the reaction process, so that the defects of high price and poor safety of the raw materials and the intermediate product with potential safety hazard generated in the reaction process in the prior art are overcome.
In addition, the method avoids complex cyclization reaction in the prior art, and has simpler process and easier industrialization.
Additional features and advantages of the invention will be set forth in the detailed description which follows.
Detailed Description
The following describes in detail specific embodiments of the present invention. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.
The invention provides a preparation method of 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compounds shown in formula (I), which comprises the following steps:
(1) carrying out chlorination reaction on 7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in formula (III) and a chlorination reagent in a first reaction medium to generate 2, 2-dichloro-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in formula (II);
(2) carrying out chlorine-fluorine exchange reaction on a 2, 2-dichloro-7-fluorine-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in a formula (II) and a fluorinating reagent;
wherein,
R1any one selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 allyl, C3-C6 haloalkyi, C3-C6 propargyl, C3-C6 halopropargyl, C1-C6 alkoxy, benzyl, methylsulfonyl and N, N-dialkylmethylsulfonyl;
R2any one selected from the group consisting of hydrogen, nitro, amino, cyano, isothiocyanato, hydrazino, and a heterocyclic ring containing 1 to 3 nitrogen atoms; the heterocyclic ring containing 1-3 nitrogens can be any one of pyrrole, pyrazole, imidazole, pyridine, pyrimidine and quinoline;
w is oxygen or sulfur.
In the step (1), the amount of the chlorinating agent used is not particularly limited, and a reaction equivalent amount of the chlorinating agent may be used. The molar ratio of the chlorinating agent to the 7-fluoro-2H-1, 4-benzoxazine-3 (4H) -one compound represented by formula (III) may be 1: (1-10), preferably 1: (1-6).
In step (1), the chlorinating agent may be any chlorinating agent used in the art for chlorination reactions. The chlorinating agent may be at least one selected from the group consisting of phosphorus pentachloride, phosphorus trichloride, chlorine gas, trichloroisocyanuric acid and sulfuryl chloride. The chlorinating agent is preferably phosphorus pentachloride. The phosphorus pentachloride can be prepared by adopting a method of in-situ reaction of phosphorus trichloride and chlorine.
In step (1), the first reaction medium is not particularly limited and is generally selected according to the solubility of the substrate. The first reaction medium may be at least one selected from the group consisting of chlorinated hydrocarbons, aromatic hydrocarbons, esters, ethers, and phosphorus trichloride. The chlorinated hydrocarbon may be at least one selected from the group consisting of dichloromethane, dichloroethane, carbon tetrachloride and tetrachloroethylene. The aromatic hydrocarbon may be at least one selected from the group consisting of toluene, xylene, and chlorobenzene. The esters may be butyl acetate and/or isopropyl acetate. The ethers may be at least one selected from the group consisting of methyl t-butyl ether, tetrahydrofuran, and methyltetrahydrofuran.
In step (1), the chlorination reaction may employ chlorination reaction conditions conventional in the art. Preferably, the chlorination reaction is carried out under conditions ranging from room temperature to heating reflux in order to increase the selectivity and conversion rate of the reaction.
In step (2), the amount of the fluorinating agent is related to the fluorination activity of the selected fluorinating agent, and the amount of the fluorinating agent is enough to ensure that the chlorine-fluorine exchange reaction is fully performed. Preferably, the amount of the fluorinating agent is 1-3 times of the reaction equivalent.
In step (2), the fluorinating reagent can be any fluorinating reagent which can convert chloromethyl on heterocycle into fluoromethyl in the field. The fluorinating agent may be at least one of hydrogen fluoride, tertiary amine salts of hydrogen fluoride, and complexes of hydrogen fluoride with nitrogen-containing agents. The tertiary amine hydrogen fluoride salt can be triethylamine hydrogen fluoride salt and/or tri-n-butylamine hydrogen fluoride salt. The complex of hydrogen fluoride with the nitrogen-containing reagent may be a pyridine hydrofluoride salt and/or a pyrrole hydrofluoride salt. The fluorinating agent is preferably at least one of hydrogen fluoride triethylamine salt, hydrogen fluoride tri-n-butylamine salt and pyridine hydrofluoride salt.
In step (2), the chloro-fluoro exchange reaction is carried out in the presence or absence of a second reaction medium. The second reaction medium is not particularly limited, and is usually selected in accordance with the solubility of the substrate, so long as the substrate is sufficiently dissolved to allow the reaction to proceed smoothly. The second reaction medium may be at least one of chlorinated hydrocarbons, aromatic hydrocarbons, esters and ethers. The chlorinated hydrocarbon may be at least one selected from the group consisting of dichloromethane, dichloroethane, carbon tetrachloride and tetrachloroethylene. The aromatic hydrocarbon may be at least one selected from the group consisting of toluene, xylene, and chlorobenzene. The esters may be butyl acetate and/or isopropyl acetate. The ethers may be at least one selected from the group consisting of methyl t-butyl ether, tetrahydrofuran, and methyltetrahydrofuran.
In step (2), the reaction temperature of the chlorine-fluorine exchange reaction is related to the fluorination activity of the selected fluorinating agent. For example, when pyridine hydrofluoride salt having a higher fluorination activity is selected, the reaction can be carried out at room temperature or lower.
According to the present invention, the compound represented by the formula (II) may be any one of the following compounds:
2, 2-dichloro-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one,
2, 2-dichloro-6-nitro-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one,
2, 2-dichloro-6-amino-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one,
2, 2-dichloro-6-isocyano-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one,
2, 2-dichloro-6-hydrazino-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -one,
2, 2-dichloro-4-propargyl-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one,
2, 2-dichloro-4-propargyl-6-nitro-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one,
2, 2-dichloro-4-propargyl-6-amino-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one,
2, 2-dichloro-4-propargyl-6-isocyano-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one and
2, 2-dichloro-4-propargyl-6-hydrazino-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one.
In the reaction, the 7-fluoro-2H-1, 4-benzoxazine-3 (4H) -one compound represented by formula (III) may be synthesized according to a conventional method in the art or commercially available (fine chemical Co., Ltd. in Jiangsu Tianshi, cat # 579-56).
According to the invention, the two-step reaction of the step (1) and the step (2) in the preparation method of the 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in the formula (I) can be used for introducing the substituent R1And R2Before or after.
The present invention will be described in detail below by way of specific examples.
In the following examples, the formula for calculating the yield of 2,2, 7-trifluoro-2H-1, 4-benzoxazin-3 (4H) -one compounds is as follows:
yield = (mole of 2,2, 7-trifluoro-2H-1, 4-benzoxazin-3 (4H) -one compound/mole of 7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one) × 100%
Example 1
This example illustrates the preparation of 2,2, 7-trifluoro-2H-1, 4-benzoxazin-3 (4H) -one.
(1) Introducing chlorine gas (7.23 g, 102 mmol) into a suspension of 7-fluoro-2H-1, 4-benzoxazine-3 (4H) -one (8.36 g, 49 mmol) in phosphorus trichloride (42 g) at room temperature; phosphorus trichloride was then recovered by atmospheric distillation to give 11.32g of a reddish brown liquid, GC/MSm/e (M +) =234.96, showing that the liquid contained 99% 2, 2-dichloro-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one (structure shown below).
Taking a small amount of reddish brown liquid, adding carbon tetrachloride into the reddish brown liquid, cooling, standing, and separating out crystals for NMR (nuclear magnetic resonance) test, wherein the NMR result is as follows: 1H-NMR (500MHz, DMSO-d6) (ppm) =2.90(br, 1H).
(2) The reddish brown liquid obtained in step (1) was added dropwise to a solution of pyridine hydrofluoride (27.92 g,100 mmol), followed by stirring at 50 ℃ for 4 hours and extraction with ethyl acetate (three extractions with 30mL of ethyl acetate each); the organic phases were combined, washed with 5% aqueous NaOH to pH 5 and ethyl acetate was removed to give 2,2, 7-trifluoro-2H-1, 4-benzoxazin-3 (4H) -one (8.63 g, 41.6 mmol) in 84.97% yield.
The appropriate amount of 2,2, 7-trifluoro-2H-1, 4-benzoxazin-3 (4H) -one was analyzed by gas chromatography-mass spectrometry (GC/MS) and NMR as follows:
GC/MSm/e(M+)=203.02；
1H-NMR(500MHz,CDCl3):(ppm)=2.90(br,1H)。
example 2
This example illustrates the preparation of 2,2, 7-trifluoro-6-nitro-2H-1, 4-benzoxazin-3 (4H) -one.
(1) Introducing chlorine gas (7.23 g, 102 mmol) into a suspension of 6-nitro-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -one (10.61 g, 49 mmol) in phosphorus trichloride (42 g) at room temperature; phosphorus trichloride was then recovered by atmospheric distillation to give 13.21g of a reddish brown liquid, GC/MSm/e (M +) =279.95, showing that the liquid contained 99% 2, 2-dichloro-6-nitro-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one (structure shown below).
Taking a small amount of reddish brown liquid, adding ethyl acetate into the reddish brown liquid, cooling, standing, and separating out crystals for NMR test, wherein the NMR result is as follows: 1H-NMR (500MHz, DMSO-d6) (ppm) =2.90(br, 1H).
(2) The reddish brown liquid obtained in step (1) was added dropwise to a solution of pyridine hydrofluoride (27.92 g,100 mmol), followed by stirring at 20 ℃ for 2 hours and extraction with dichloromethane (three extractions with 30mL of dichloromethane each); the organic phases were combined, washed with 5% aqueous NaOH to pH 6 and dichloromethane was removed to give 2,2, 7-trifluoro-6-nitro-2H-1, 4-benzoxazin-3 (4H) -one (10.42 g, 41.16 mmol) as a brown solid in 83.99% yield.
GC/MS analysis and NMR analysis were carried out on the appropriate amount of 2,2, 7-trifluoro-6-nitro-2H-1, 4-benzoxazin-3 (4H) -one, and the results were as follows:
GC/MSm/e(M+)=248.12；
1H-NMR(500MHz,CDCl3):(ppm)=2.90(br,1H),7.15(d,1H),7.80(d,1H)。
example 3
This example illustrates the preparation of 2,2, 7-trifluoro-6-amino-2H-1, 4-benzoxazin-3 (4H) -one.
(1) Introducing chlorine gas (7.23 g, 102 mmol) into a suspension of 6-amino-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -one (9.11 g, 49 mmol) in phosphorus trichloride (42 g) at room temperature; phosphorus trichloride was then recovered by atmospheric distillation to give 11.55g of a reddish brown liquid, GC/MSm/e (M +) =251.04, showing that the liquid contained 98% 2, 2-dichloro-6-amino-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one (structure shown below).
Taking a small amount of reddish brown liquid, adding the reddish brown liquid into ethyl acetate, cooling, standing, and separating out crystals for NMR test, wherein the NMR result is as follows: 1H-NMR (500MHz, DMSO-d6) (ppm) =2.90(br, 1H).
(2) Dropwise adding the reddish brown liquid obtained in the step (1) into a pyridine hydrofluoride (27.92 g,100 mmol) solution, and then stirring at 18 ℃ for 2 hours; the reaction was poured into 5% aqueous NaOH, pH adjusted to 8, and filtered to give 2,2, 7-trifluoro-6-amino-2H-1, 4-benzoxazin-3 (4H) -one (8.94 g, 40.17 mmol) as a brown solid in 81.97% yield.
GC/MS analysis and NMR analysis were carried out on the appropriate amount of 2,2, 7-trifluoro-6-amino-2H-1, 4-benzoxazin-3 (4H) -one, and the results were as follows:
GC/MSm/e(M+)=218.03；
1H-NMR(500MHz,DMSO-d6):(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):(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)。
example 4
This example illustrates the preparation of 2,2, 7-trifluoro-4-propargyl-6-amino-2H-1, 4-benzoxazin-3 (4H) -one.
(1) Introducing chlorine gas (7.23 g, 102 mmol) into a suspension of 4-propargyl-6-amino-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -one (11.01 g, 32.17 mmol) in phosphorus trichloride (42 g) at room temperature; phosphorus trichloride was then recovered by atmospheric distillation to give 13.00g of a reddish brown liquid, GC/MSm/e (M +) =287.99, showing that the liquid contained 98% 2, 2-dichloro-4-propargyl-6-amino-7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one (structure shown below).
Taking a small amount of reddish brown liquid, adding the reddish brown liquid into dichloroethane, cooling, standing, and separating out crystals for NMR test, wherein the NMR result is as follows: 1H-NMR (500MHz, DMSO-d6) (ppm) =2.90(br, 1H).
(2) Dropwise adding the reddish brown liquid obtained in the step (1) into a pyridine hydrofluoride (27.92 g,100 mmol) solution, and then stirring at 20 ℃ for 2 hours; extraction with ethyl acetate (three times with 30mL of ethyl acetate each time); the organic phases were combined, washed with 5% aqueous NaOH to pH 7 and ethyl acetate was removed to give 2,2, 7-trifluoro-4-propargyl-6-amino-2H-1, 4-benzoxazin-3 (4H) -one (6.87 g, 25.74 mmol) in 80% yield. It was recrystallized from methanol to give light yellow to white crystals, melting point: 239.2 deg.C.
The appropriate amount of 2,2, 7-trifluoro-4-propargyl-6-amino-2H-1, 4-benzoxazin-3 (4H) -one was analyzed by liquid chromatography-mass spectrometry (LC/MS) and NMR as follows:
LC/MSm/e(M+)=256.05；
1H-NMR(500MHz,DMSO-d6):(ppm)=3.45(s,1H),4.74(s,2H),5.42(s,2H),6.85(d,1H),7.26(d,1H)。
example 5
This example illustrates the preparation of 2- (2,2, 7-trifluoro-3-oxo-4-propargyl-3, 4-dihydro-2H-benzo [ b ] [1,4] oxazin-6-yl) -4,5,6, 7-tetrahydro-1H-isoindole-1, 3(2H) -dione.
(1) Introducing chlorine gas (7.23 g, 102 mmol) into a suspension of 2- (7-fluoro-3-oxo-4-propargyl-3, 4-dihydro-2H-benzo [ b ] [1,4] oxazin-6-yl) -4,5,6, 7-tetrahydro-1H-isoindole-1, 3(2H) -dione (11.01 g,30.45 mmol) (with the structure shown in formula 51) in phosphorus trichloride (42 g) at room temperature; phosphorus trichloride was then recovered by atmospheric distillation to give 11.72g of a reddish brown liquid, GC/MSm/e (M +) =287.99, showing that the liquid contained 98% 2- (2, 2-dichloro-7-fluoro-3-oxo-3, 4-dihydro-2H-benzo [ b ] [1,4] oxazin-6-yl) -4,5,6, 7-tetrahydro-1H-isoindole-1, 3(2H) -dione (structure shown in formula 52).
Taking a small amount of reddish brown liquid, adding the reddish brown liquid into ethyl acetate, cooling, standing, and separating out crystals for NMR test, wherein the NMR result is as follows: 1H-NMR (500MHz, DMSO-d6) (ppm) =2.90(br, 1H).
(2) Dropwise adding the reddish brown liquid obtained in the step (1) into a pyridine hydrofluoride (27.92 g,100 mmol) solution, and then stirring at 20 ℃ for 2 hours; extraction with ethyl acetate (three times with 30mL of ethyl acetate each time); the organic phases were combined, washed with 5% aqueous NaOH solution to pH 7, and ethyl acetate was removed to give 2- (2,2, 7-trifluoro-2-ethyl acetate)-3-oxo-4-propargyl-3, 4-dihydro-2H-benzo [ b][1,4]Oxazin-6-yl) -4,5,6, 7-tetrahydro-1H-isoindole-1, 3(2H) -dione (9.7 g, 24.36 mmol), yield 80%. It was recrystallized from methanol to give white crystals, melting point: 239.2 ℃, boiling point: 605.8 + -55 deg.C (760torr), density 1.57 + -0.1 g/cm3。
An appropriate amount of 2,2, 7-trifluoro-4-propargyl-6-amino-2H-1, 4-benzoxazin-3 (4H) -one was taken for LC/MS analysis and NMR analysis, and the results were as follows:
LC/MSm/e(M+)=256.05；
1H-NMR(500MHz,DMSO-d6):(ppm)=3.45(s,1H),4.74(s,2H),5.42(s,2H),6.85(d,1H),7.26(d,1H)。
it can be seen from the results of the above examples that according to the process of the present invention, a higher product yield can be obtained. Meanwhile, because the raw materials used in the method are safe and easy to obtain, an intermediate product with potential safety hazard cannot be generated in the reaction process, and the defects that the raw materials are expensive and poor in safety and the intermediate product with potential safety hazard is generated in the reaction process in the prior art are overcome. The method of the invention has no complex cyclization reaction, so the operation method is simpler and is easier for industrialization.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.

Claims (7)

1. A method for preparing 2,2, 7-trifluoro-2H-1, 4-benzoxazine-3 (4H) -one compounds represented by formula (I), which comprises the following steps:
(1) carrying out chlorination reaction on 7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in formula (III) and a chlorination reagent in a first reaction medium to generate 2, 2-dichloro-7-fluoro-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in formula (II);
(2) carrying out chlorine-fluorine exchange reaction on a 2, 2-dichloro-7-fluorine-2H-1, 4-benzoxazine-3 (4H) -ketone compound shown in a formula (II) and a fluorinating reagent;
wherein,
R1any one selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 allyl, C3-C6 haloalkyi, C3-C6 propargyl, C3-C6 halopropargyl, C1-C6 alkoxy, benzyl, methylsulfonyl and N, N-dialkylmethylsulfonyl;
R2any one selected from the group consisting of hydrogen, nitro, amino, cyano, isothiocyanato, hydrazino, and a heterocyclic ring containing 1 to 3 nitrogen atoms;
w is oxygen or sulfur; wherein,
in the step (1), the chlorinating agent is at least one selected from phosphorus pentachloride, phosphorus trichloride, chlorine, trichloroisocyanuric acid and sulfuryl chloride;
in the step (1), the first reaction medium is selected from at least one of chlorohydrocarbon, aromatic hydrocarbon, esters, ethers and phosphorus trichloride;
in the step (2), the fluorinating agent is at least one of hydrogen fluoride, tertiary amine hydrogen fluoride salt and a complex of hydrogen fluoride and a nitrogen-containing reagent.
2. The process according to claim 1, wherein in step (1), the molar ratio of the chlorinating agent to the 7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one compound represented by formula (III) is 1: (1-10).
3. The process according to claim 2, wherein in step (1), the molar ratio of the chlorinating agent to the 7-fluoro-2H-1, 4-benzoxazin-3 (4H) -one compound represented by formula (III) is 1: (1-6).
4. The process according to claim 1, wherein, in the step (1), the chlorination reaction is carried out under a state of room temperature to heated reflux.
5. The method according to claim 1, wherein in the step (2), the amount of the fluorinating agent is 1 to 3 times of the reaction equivalent.
6. The process according to claim 1, wherein the tertiary amine hydrogen fluoride salt is triethylamine hydrogen fluoride salt and/or tri-n-butylamine hydrogen fluoride salt and the complex of hydrogen fluoride with a nitrogen-containing reagent is pyridine hydrofluoride salt and/or pyrrole hydrofluoride salt.
7. The method of claim 1, wherein the chloro-fluoro exchange reaction of step (2) is carried out in the presence or absence of a second reaction medium, the second reaction medium being at least one of chlorinated hydrocarbons, aromatic hydrocarbons, esters, and ethers.
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