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CN116199701A - Pyrazolooxazinone compound prepared based on intramolecular free radical cycloaddition and preparation method thereof - Google Patents

Pyrazolooxazinone compound prepared based on intramolecular free radical cycloaddition and preparation method thereof Download PDF

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CN116199701A
CN116199701A CN202310195680.6A CN202310195680A CN116199701A CN 116199701 A CN116199701 A CN 116199701A CN 202310195680 A CN202310195680 A CN 202310195680A CN 116199701 A CN116199701 A CN 116199701A
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王斌
李馨悦
罗绅绅
方玉华
薛雨慧
雍婷婷
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Anhui University of Traditional Chinese Medicine AHUTCM
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Abstract

The invention relates to a method for preparing pyrazolooxazinone compounds based on intramolecular free radical cycloaddition, which adopts free radical cycloaddition reaction to synthesize the pyrazolooxazinone compounds in one step, wherein two nitrogen atoms on a pyrazole ring in a reaction product come from benzenesulfonyl hydrazide molecules, the safety is good, the synthetic route does not need high-temperature reflux, and the reaction is energy-saving and green; the catalyst may be a nonmetallic catalyst PhI (OAc) 2 The method avoids the environmental pollution problems such as toxic metal lead acetate or metal residue, and the reaction can be carried out in an acidic environment or an alkaline environment.

Description

Pyrazolooxazinone compound prepared based on intramolecular free radical cycloaddition and preparation method thereof
Technical Field
The invention belongs to the field of chemical synthesis, and in particular relates to pyrazolooxazinone compounds and a preparation method thereof.
Background
Oxazinone is a novel heterocyclic herbicide, has systemic conductivity, is mainly absorbed by roots and stem leaf bases of weeds, and can prevent annual gramineous weeds such as dried golden seeds, barnyard grass, heterotypic nutgrass galingale and the like by preventing the formation of plant endogenous GA3 hormone, so that the stems and leaves of the weeds are green, and the growth is inhibited until the weeds die. However, oxazin has poor control effect on broadleaf weeds, and can not completely and effectively control paddy field weeds when being used alone, so that other products are often required to be compounded for use in order to enlarge the weed killing spectrum.
Figure BDA0004107903900000011
The synthetic route of oxazin mainly comprises 2 steps:
route 1: 3, 5-dichlorobenzoic acid is used as a raw material to react with thionyl chloride to prepare 3, 5-dichlorobenzoyl chloride, the 3, 5-dichlorobenzoyl chloride is obtained through hydrogen reduction, the 3, 5-dichlorobenzoyl chloride is obtained through substitution by hydrochloric acid, the 3, 5-dichlorobenzoyl chloride is obtained through reaction with sodium cyanide, the 3, 5-dichlorobenzonitrile is obtained through reaction, the dimethyl substituted benzonitrile of the 3, 5-dichlorobenzonitrile is prepared through reaction with methyl iodide, the amide is hydrolyzed by hydrolysis, the 1-methyl-1- (3, 5-dichlorophenyl) ethylamine is obtained through Huffman degradation, and finally the N-methylene-1-methyl-1- (3, 5-dichlorophenyl) ethylamine is generated by formaldehyde. The preparation method comprises the steps of taking phenyl ethyl acetate as a raw material and carrying out claisen reaction on the phenyl ethyl acetate to obtain 3-phenyl acetoacetate, hydrolyzing the 3-phenyl acetoacetate, and then reacting the 3-phenyl acetoacetate with acetone to obtain 5-phenyl-2, 6-trimethyl-2H, 4H-1, 3-dioxin-4-ketone. Reacting 5-phenyl-2, 6-trimethyl-2H, 4H-1, 3-dioxin-4-ketone with N-methylene-1-methyl-1- (3, 5-dichlorophenyl) ethylamine to obtain oxazinone:
Figure BDA0004107903900000021
the synthesis condition of the route is simpler, but the steps are too long, the total yield is lower, naCN is used in the reaction, the toxicity is high, and the safety is poor.
Route 2: 3, 5-dichlorobenzoic acid is used as a raw material, reacts with thionyl chloride to prepare 3, 5-dichlorobenzoyl chloride, reacts with acetonitrile to prepare dimethyl-substituted benzyl alcohol, reacts with acetonitrile to prepare N- [ 1-methyl-1- (3, 5-dichlorophenyl) ethyl ] acetamide, hydrolyzes to obtain 1-methyl-1- (3, 5-dichlorophenyl) ethylamine, and finally reacts with formaldehyde to generate N-methylene-1-methyl-1- (3, 5-dichlorophenyl) ethylamine. The ethyl phenylacetate is taken as a raw material to react with ethyl acetate to obtain the 3-phenyl acetoacetic acid ethyl ester through claisen reaction. 3-phenyl acetoacetic acid ethyl ester reacts with N-methylene-1-methyl-1- (3, 5-dichlorophenyl) ethylamine to prepare oxazinone. 3-phenyl acetoacetic acid ethyl ester reacts with N-methylene-1-methyl-1- (3, 5-dichlorophenyl) ethylamine to prepare oxazinone:
Figure BDA0004107903900000031
the route conditions are relatively mild, but the route is still long.
Disclosure of Invention
Based on the above problems, the object of the present invention is to provide pyrazolooxazinone compounds having a completely new structure and a method for preparing the pyrazolooxazinone compounds based on intramolecular free radical cycloaddition.
The inventor of the invention discovers a new route which is completely different from the existing oxazinone synthesis method, adopts a free radical cycloaddition reaction to realize the synthesis of a target object in one step, and ensures that two nitrogen atoms on a pyrazole ring in a reaction product come from benzenesulfonyl hydrazide molecules rather than hydrazine hydrate molecules which are easy to explosion and has good safety. Through investigation of reaction conditions and yield, the synthetic route of the invention can well perform reaction at 25 ℃, does not need high-temperature reflux, and has the advantages of energy conservation and environmental protection; the catalyst may be a nonmetallic catalyst PhI (OAc) 2 The environmental pollution problems of toxic metal lead acetate or metal residues (copper ions in copper catalytic reaction) and the like are avoided; the reaction can be carried out in an acidic environment (such as acetic acid) or an alkaline environment (such as sodium carbonate), and the application prospect is wide.
The reaction mechanism of the synthetic route in the invention is as follows:
Figure BDA0004107903900000041
specifically, the present invention provides a compound having the following general structure:
Figure BDA0004107903900000042
wherein R is 1 、R 2 Each independently H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, phenoxy or halogen.
Preferably, R 1 Is H, C C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, phenoxy or halogen, R 2 H, C1 is C1-C6 alkyl, C1-C6 alkoxy or halogen.
More preferably, R 1 Is H, methyl, ethyl, phenoxy, diethylamino, fluoro or chloro, R 2 Is H, methyl, ethyl, fluorine or chlorine.
The compound specifically comprises a compound with the following structure:
Figure BDA0004107903900000043
Figure BDA0004107903900000051
the invention also provides a synthesis method of the compound:
the phenylsulfonyl hydrazone compound with the structure shown below, an oxidant and acid or alkali are reacted in a solvent.
Figure BDA0004107903900000052
In the method, the solvent is selected from one or more of tetrahydrofuran, DMF, acetone, DMAC and DMSO; the oxidant is selected from TBHP, DTBP, TBN, phI(OAc) 2 One or more of the following; the acid is selected from one or more of formic acid, acetic acid and fluoboric acid; the alkali is selected from one or more of sodium carbonate, sodium acetate, triethylamine, DMAP and potassium phosphate.
In the method, the molar ratio of the benzenesulfonyl hydrazone compound to the oxidant is 1-5:1-5:0.1-10, preferably 1-2:2-5:5-10, more preferably 1:2:10.
In the process, the reaction temperature is 20℃to 120℃and preferably 25℃50℃80℃105 ℃.
In the method, the reaction time is 2-24h, preferably 2h,4h,6h,8h,10h,12h and 24h.
The benzenesulfonyl hydrazone compound used in the present invention can be prepared by the following method:
Figure BDA0004107903900000053
Figure BDA0004107903900000061
the invention has the following advantages: 1. the synthesis of the target object is realized in one step by adopting a free radical cycloaddition reaction, and the design idea is innovative; 2. the reaction can be well carried out at 25 ℃, the condition is mild, and the reaction is energy-saving and green; 3. with nonmetallic catalysts PhI (OAc) 2 The environmental pollution problems such as toxic metal or metal residue are avoided; 4. the reaction can be carried out in an acidic environment (such as acetic acid) or an alkaline environment (such as sodium carbonate), and the application prospect is wide; 5. the two nitrogen atoms on the pyrazole ring in the reaction product come from benzenesulfonyl hydrazine molecules instead of hydrazine hydrate molecules which are easy to explosion, so that the safety is good; 6. the application range of the substrate is wider, and substrates with different substituent groups can be used; 7. no method for synthesizing the compound is reported at home and abroad.
Drawings
FIG. 1 is a schematic diagram of a synthetic route of the present invention;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of the compound B of the present invention;
FIG. 3 is a nuclear magnetic resonance spectrum of the compound B of the present invention;
FIG. 4 shows a compound B of the present invention 1 Nuclear magnetic hydrogen spectrogram of (2);
FIG. 5 shows a compound B of the present invention 1 Nuclear magnetic carbon spectrogram of (2);
FIG. 6 shows a compound B of the present invention 1 A crystal structure diagram of (2);
FIG. 7 shows a compound B of the present invention 2 Nuclear magnetic hydrogen spectrogram of (2);
FIG. 8 shows a compound B of the present invention 2 Nuclear magnetic carbon spectrogram of (2);
FIG. 9 shows a compound B of the present invention 3 Nuclear magnetic hydrogen spectrogram of (2);
FIG. 10 shows a compound B of the present invention 3 Nuclear magnetic carbon spectrogram of (2);
FIG. 11 shows a compound B of the present invention 4 Nuclear magnetic hydrogen spectrogram of (2);
FIG. 12 shows a compound B of the present invention 4 Nuclear magnetic carbon spectrogram of (2);
FIG. 13 shows a compound B of the present invention 5 Nuclear magnetic hydrogen spectrogram of (2);
FIG. 14 shows a compound B of the present invention 5 Nuclear magnetic carbon spectrogram of (2);
FIG. 15 shows a compound B of the present invention 6 Nuclear magnetic hydrogen spectrogram of (2);
FIG. 16 shows a compound B of the present invention 6 Nuclear magnetic carbon spectrogram of (2);
FIG. 17 shows a compound B of the present invention 7 Nuclear magnetic hydrogen spectrogram of (2);
FIG. 18 shows a compound B of the present invention 7 Nuclear magnetic carbon spectrogram of (2).
Detailed Description
Example 1 verification of synthetic route
Synthetic ortho-substituted benzenesulfonylhydrazone Compound A (10.5 mg,0.025 mmol) and the oxidant iodobenzene acetate (PhI (OAc) 2 16.1mg,0.05 mmol) of N, N-Dimethylacetamide (DMAC)/glacial acetic acid=10:1, (V/V) as a solvent, and stirring at 25 ℃ for 3H to obtain the target compound 2-phenyl-9H-benzol [ e ]]pyrazolo[5,1-b][1,3]oxazin-9-one (compound B) is reacted as follows (i.e., FIG. 1 of the specification).
Figure BDA0004107903900000071
The structure of the compound B is verified through nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum, and the structure is shown in the accompanying figures 2 and 3 of the specification.
Example 2 optimization of reaction conditions
With reference to the starting materials of example 1, the reaction solvent (tetrahydrofuran, DMF, acetone, DMAC, DMSO), the oxidant (TBHP, DTBP, TBN, phI (OAc) was reacted in the same amount as the starting materials 2 ) The screening is carried out on the parameters of acid (formic acid, acetic acid, fluoroboric acid) or alkali (sodium carbonate, sodium acetate, triethylamine, DMAP, potassium phosphate), the reaction temperature (25 ℃,50 ℃,80 ℃,105 ℃) and the reaction time (2 h,4h,6h,8h,10h,12h,24 h) and the like, the process is shown as follows, and the screening results are shown in Table 1.
Figure BDA0004107903900000072
Table 1 optimization of Synthesis conditions for Compound B yield
Figure BDA0004107903900000081
[a]conditions:A(0.25mmol),PhI(OAc) 2 (0.5mmol),Acid(2.5mmol),Solvent(0.5mL),4.0h,air.
[b]Isolated yields based on A after chromatography.
Conclusion: when DMAC is used as solvent, phI (OAc) is used 2 As an oxidizing agent, acetic acid was used, the reaction time was controlled at 25 ℃, the yield at 12 hours was optimal, and the target B was obtained in 88% yield.
Example 3 expansion of reaction substrates
To verify the applicability of the above reaction, the reaction was performed using substrates of different substituents, and it was found that all of them can be applied to the reaction scheme to obtain the following reaction products:
Figure BDA0004107903900000082
Figure BDA0004107903900000083
Figure BDA0004107903900000091
compound B 1 -B 7 The specific preparation process of (2) is as follows:
B 1 step1: weighing C 1 (2 mmol), 3-phenylpropionic acid (2.2 mmol) and DMAP (0.15 mmol) were placed in a Schlenk tube (stirring bar was added), 2mL of anhydrous dichloromethane was added, placed in a magnetic stirrer for ice bath, and cooled to 0 ℃; another flask was taken and EDC (1 mmol) was taken with 1mL CH 2 CL 2 Dissolving. The mixture was added dropwise and reacted at 30℃for 12 hours to give a yellow clear solution. The yield was 24.5%.
Step2: paraphthalenesulfonyl hydrazine (0.72 mmol) was weighed into a flask (with stirring) and 3.75mL of methanol was added, dissolved in an oil bath at 60℃and cooled to room temperature. Another flask was taken to weigh substrate D 1 (0.6mmol)CH 2 Cl 2 Dissolving, dropwise adding by a glass dropper, and stirring at room temperature for reaction for 3h. The yield was 86.4%.
Step3: weighing A 1 (0.45 mmol) and the oxidant iodobenzene diacetic acid (0.99 mmol) were placed in a Schlenk tube (with stirring), and 4.5mL of DMF and 450. Mu.L of glacial acetic acid were added with stirring at room temperature and the temperature was raised to 25℃again for reaction for 12h. The yield was 58%.
B 2 Step1: weighing C 2 (2 mmol), 3-phenylpropionic acid (2.2 mmol) and DMAP (0.15 mmol) were placed in a Schlenk tube (stirring bar was added), 2mL of anhydrous dichloromethane was added, placed in a magnetic stirrer for ice bath, and cooled to 0 ℃; another flask was taken and EDC (1 mmol) was taken with 1mL CH 2 CL 2 Dissolving. The mixture was added dropwise and reacted at 30℃for 12 hours to give a yellow clear solution. The yield was 18.5%.
Step2: weighing p-toluenesulfonylHydrazine (0.72 mmol) was dissolved in a flask (with stirring) with 3.75mL of methanol in an oil bath at 60℃and cooled to room temperature. Another flask was taken to weigh substrate D 2 (0.6mmol)CH 2 Cl 2 Dissolving, dropwise adding by a glass dropper, and stirring at room temperature for reaction for 3h. The yield was 89.6%.
Step3: weighing A 2 (0.45 mmol) and the oxidant iodobenzene diacetic acid (0.99 mmol) were placed in a Schlenk tube (with stirring), and 4.5mL of DMF and 450. Mu.L of glacial acetic acid were added with stirring at room temperature and the temperature was raised to 25℃again for reaction for 12h. The yield was 52%.
B 5 Step1: weighing C 5 (2 mmol), 3-phenylpropionic acid (2.2 mmol) and DMAP (0.15 mmol) were placed in a Schlenk tube (stirring bar was added), 2mL of anhydrous dichloromethane was added, placed in a magnetic stirrer for ice bath, and cooled to 0 ℃; another flask was taken and EDC (1 mmol) was taken with 1mL CH 2 CL 2 Dissolving. The mixture was added dropwise and reacted at 30℃for 12 hours to give a yellow clear solution. The yield was 15.7%.
Step2: paraphthalenesulfonyl hydrazine (0.72 mmol) was weighed into a flask (with stirring) and 3.75mL of methanol was added, dissolved in an oil bath at 60℃and cooled to room temperature. Another flask was taken to weigh substrate D 5 (0.6mmol)CH 2 Cl 2 Dissolving, dropwise adding by a glass dropper, and stirring at room temperature for reaction for 3h. The yield was 82.3%.
Step3: weighing A 5 (0.45 mmol) and the oxidant iodobenzene diacetic acid (0.99 mmol) were placed in a Schlenk tube (with stirring), and 4.5mL of DMF and 450. Mu.L of glacial acetic acid were added with stirring at room temperature and the temperature was raised to 25℃again for reaction for 12h. The yield was 59.2%.
B 3 Step1: paraphthalenesulfonyl hydrazine (0.72 mmol) was weighed into a flask (with stirring) and 3.75mL of methanol was added, dissolved in an oil bath at 60℃and cooled to room temperature. Another flask was taken to weigh substrate C 3 (0.6mmol)CH 2 Cl 2 Dissolving, dropwise adding by a glass dropper, and stirring at room temperature for reaction for 3h. The yield was 92.7%.
Step2: weighing D 3 (2 mmol), 3-phenylpropionic acid (2.2 mmol) and DMAP (0.15 mmol) were placed in a Schlenk tube (stirring bar was added), 2mL of anhydrous dichloromethane was added, placed in a magnetic stirrer for ice bath, and cooled to 0 ℃; in addition, anotherA flask was taken and EDC (1 mmol) was taken with 1mL CH 2 CL 2 Dissolving. The mixture was added dropwise and reacted at 30℃for 12 hours to give a yellow clear solution. The yield was 26.7%.
Step3: weighing A 3 (0.45 mmol) and the oxidant iodobenzene diacetic acid (0.99 mmol) were placed in a Schlenk tube (with stirring), and 4.5mL of DMF and 450. Mu.L of glacial acetic acid were added with stirring at room temperature and the temperature was raised to 25℃again for reaction for 12h. The yield was 50.2%.
B 4 Step1: paraphthalenesulfonyl hydrazine (0.72 mmol) was weighed into a flask (with stirring) and 3.75mL of methanol was added, dissolved in an oil bath at 60℃and cooled to room temperature. Another flask was taken to weigh substrate C 4 (0.6mmol)CH 2 Cl 2 Dissolving, dropwise adding by a glass dropper, and stirring at room temperature for reaction for 3h. The yield was 89.5%.
Step2: weighing D 4 (2 mmol), 3-phenylpropionic acid (2.2 mmol) and DMAP (0.15 mmol) were placed in a Schlenk tube (stirring bar was added), 2mL of anhydrous dichloromethane was added, placed in a magnetic stirrer for ice bath, and cooled to 0 ℃; another flask was taken and EDC (1 mmol) was taken with 1mL CH 2 CL 2 Dissolving. The mixture was added dropwise and reacted at 30℃for 12 hours to give a yellow clear solution. The yield was 23.6%.
Step3: weighing A 4 (0.45 mmol) and the oxidant iodobenzene diacetic acid (0.99 mmol) were placed in a Schlenk tube (with stirring), and 4.5mL of DMF and 450. Mu.L of glacial acetic acid were added with stirring at room temperature and the temperature was raised to 25℃again for reaction for 12h. The yield was 44.2%.
B 6 Step1: paraphthalenesulfonyl hydrazine (0.72 mmol) was weighed into a flask (with stirring) and 3.75mL of methanol was added, dissolved in an oil bath at 60℃and cooled to room temperature. Another flask was taken to weigh substrate C 6 (0.6mmol)CH 2 Cl 2 Dissolving, dropwise adding by a glass dropper, and stirring at room temperature for reaction for 3h. The yield was 92.5%.
Step2: weighing D 6 (2 mmol), 3-phenylpropionic acid (2.2 mmol) and DMAP (0.15 mmol) were placed in a Schlenk tube (stirring bar was added), 2mL of anhydrous dichloromethane was added, placed in a magnetic stirrer for ice bath, and cooled to 0 ℃; another flask was taken and EDC (1 mmol) was taken with 1mL CH 2 CL 2 Dissolving. The mixed solution is added dropwise and reversely at 30 DEG CThe reaction time was 12h, and a yellow clear solution was obtained. The yield was 18.9%.
Step3: weighing A 6 (0.45 mmol) and the oxidant iodobenzene diacetic acid (0.99 mmol) were placed in a Schlenk tube (with stirring), and 4.5mL of DMF and 450. Mu.L of glacial acetic acid were added with stirring at room temperature and the temperature was raised to 25℃again for reaction for 12h. The yield was 53.2%.
B 7 Step1: paraphthalenesulfonyl hydrazine (0.72 mmol) was weighed into a flask (with stirring) and 3.75mL of methanol was added, dissolved in an oil bath at 60℃and cooled to room temperature. Another flask was taken to weigh substrate C 7 (0.6mmol)CH 2 Cl 2 Dissolving, dropwise adding by a glass dropper, and stirring at room temperature for reaction for 3h. The yield was 92.3%.
Step2: weighing D 7 (2 mmol), 3-phenylpropionic acid (2.2 mmol) and DMAP (0.15 mmol) were placed in a Schlenk tube (stirring bar was added), 2mL of anhydrous dichloromethane was added, placed in a magnetic stirrer for ice bath, and cooled to 0 ℃; another flask was taken and EDC (1 mmol) was taken with 1mL CH 2 CL 2 Dissolving. The mixture was added dropwise and reacted at 30℃for 12 hours to give a yellow clear solution. The yield was 21.4%.
Step3: weighing A 7 (0.45 mmol) and the oxidant iodobenzene diacetic acid (0.99 mmol) were placed in a Schlenk tube (with stirring), and 4.5mL of DMF and 450. Mu.L of glacial acetic acid were added with stirring at room temperature and the temperature was raised to 25℃again for reaction for 12h. The yield was 47.5%.
The compound B prepared 1 -B 7 The structure is as follows:
Figure BDA0004107903900000111
for the above compound B 1 -B 7 The structure verification is carried out through nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum, and the structure verification is respectively shown in figures 4-17 of the attached drawings.
Compound B therein by X-ray single crystal diffraction 1 The analysis of the crystal structure was performed as shown in fig. 18 of the specification.
Verification of Effect of the Compounds of example 4
The test method comprises the following steps: plate method
Compound B of example 3 5 Adding acetone to dissolve to prepare homogeneous solution, and adding appropriate amount of 0.1% Tween-80 to dilute to 50 mg/L. Soaking barnyard grass seeds in 25 ℃ water for 12 hours, placing the soaked seeds in a culture dish filled with wet filter paper, and accelerating germination at 35 ℃ until white buds are exposed for later use.
2 pieces of filter paper are filled in a culture dish with the diameter of 9cm, 20 seeds with consistent germination conditions are respectively selected and placed in the culture dish, the direction of radicle and embryo of the seeds is kept consistent, 10mL of liquid medicine is added into the culture dish, a blank control group is added with acetone solvent without compound, the culture is carried out in a greenhouse incubator for 5 days, each concentration is repeated for 3 times, and the root length, fresh weight and dry weight of crops are measured in time after 5 days. The effect of the compound of interest on the growth of the target crop is evaluated in terms of the rate of promotion over the length of the root (or stem).
The calculation formula for correcting the root length (stem length) growth promotion rate is as follows:
Figure BDA0004107903900000121
r-correct root length (stem length) growth rate;
L 0 control root length (stem length);
L 1 -treating root length (stem length);
L S solvent control root length (stem length);
the units are percentages, two digits after the decimal point are reserved.
The results are shown in Table 2.
TABLE 2 Compound B 5 Growth inhibition effect on barnyard grass at different concentrations
Concentration of 0.1μg/ml 1μg/ml 10μg/ml
Inhibition rate% 21.05 35.67 60.25

Claims (10)

1. A compound having the general structure shown below:
Figure FDA0004107903880000011
wherein R is 1 、R 2 Each independently H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, phenoxy or halogen.
2. The compound of claim 1, wherein R 1 H, C1 is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamino, phenoxy or halogen; r is R 2 H, C1 is C1-C6 alkyl, C1-C6 alkoxy or halogen.
3. The compound of claim 1, wherein R 1 Is H, methyl, ethyl, phenoxy, diethylamino, fluoro or chloro, R 2 Is H, methyl, ethyl, fluorine or chlorine.
4. The compound of claim 1, which is:
Figure FDA0004107903880000012
5. the process for producing a compound according to any one of claims 1 to 4, wherein a benzenesulfonylhydrazone compound having the structure shown below is reacted with an oxidizing agent and an acid or base in a solvent:
Figure FDA0004107903880000021
6. the method of claim 5, wherein the solvent is selected from one or more of tetrahydrofuran, DMF, acetone, DMAC, DMSO.
7. The method of claim 5, wherein the oxidizing agent is selected from the group consisting of TBHP, DTBP, TBN, phI (OAc) 2 One or more of the following.
8. The method of claim 5, wherein the acid is selected from one or more of formic acid, acetic acid, fluoroboric acid; the alkali is selected from one or more of sodium carbonate, sodium acetate, triethylamine, DMAP and potassium phosphate.
9. The process according to claim 5, wherein the molar ratio of benzenesulfonylhydrazone compound to oxidant is 1-5:1-5:0.1-10, preferably 1-2:2-5:5-10, more preferably 1:2:10.
10. The process of claim 5, wherein the reaction temperature is 20℃to 120℃and the reaction time is 2 to 24 hours.
CN202310195680.6A 2023-02-27 2023-02-27 Pyrazolooxazinone compound prepared based on intramolecular free radical cycloaddition and preparation method thereof Pending CN116199701A (en)

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US20200165236A1 (en) * 2017-07-28 2020-05-28 Yuhan Corporation Improved process for preparing aminopyrimidine derivatives
CN114634516A (en) * 2022-03-17 2022-06-17 安徽中医药大学 Coumarin pyrazole compound and preparation method thereof

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US20200165236A1 (en) * 2017-07-28 2020-05-28 Yuhan Corporation Improved process for preparing aminopyrimidine derivatives
CN114634516A (en) * 2022-03-17 2022-06-17 安徽中医药大学 Coumarin pyrazole compound and preparation method thereof

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PANT, U. C., ET AL: "Studies on 1-hydroxy-2-naphthoic and 3-hydroxy-2-naphthoic acid hydrazides", REVUE ROUMAINE DE CHIMIE, vol. 24, no. 3, 31 December 1979 (1979-12-31), pages 471 - 482 *

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