CN101973956B - Methods for synthesizing isatoic anhydride and N-isopropyl-2-aminobenzamide - Google Patents
Methods for synthesizing isatoic anhydride and N-isopropyl-2-aminobenzamide Download PDFInfo
- Publication number
- CN101973956B CN101973956B CN 201010297432 CN201010297432A CN101973956B CN 101973956 B CN101973956 B CN 101973956B CN 201010297432 CN201010297432 CN 201010297432 CN 201010297432 A CN201010297432 A CN 201010297432A CN 101973956 B CN101973956 B CN 101973956B
- Authority
- CN
- China
- Prior art keywords
- trichloromethyl
- solution
- isatoic anhydride
- aminobenzamide
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Abstract
The invention provides a method for synthesizing isatoic anhydride, comprising the steps of: dropwise adding a di(trichloromethyl) carbonic ester solution into an o-aminobenzoic acid solution, refluxing for reaction to obtain the isatoic anhydride. The invention further also provides a method for synthesizing N-isopropyl-2-aminobenzamide, comprising the steps of: a) dropwise adding the di(trichloromethyl) carbonic ester solution into the o-aminobenzoic acid solution, and refluxing for reaction to obtain an isatoic anhydride solution; and b) dropwise adding isopropamide into the isatoic anhydride solution, and reacting to obtain the N-isopropyl-2-aminobenzamide. After o-aminobenzoic acid and di(trichloromethyl) carbonic ester react in an organic solvent to generate the isatoic anhydride, the N-isopropyl-2-aminobenzamide can be obtained by directly adding the isopropamide for amidation, without carrying out the steps of extraction, purification, drying and the like on the isatoic anhydride, therefore, operation steps are reduced, production cycle is shortened, and industrialized production is easy to realize.
Description
Technical field
The present invention relates to the pesticide intermediate compound technical, relate in particular to a kind of synthetic method of isatoic anhydride and the synthetic method of N-sec.-propyl-2-aminobenzamide.
Background technology
Isatoic anhydride is named again and relies on acid anhydrides, N-carboxylic O amine benzoic anhydride, carboxylic O amine benzoic anhydride, and English name is 4H-3,1-benzoxazine-2,4 (1H)-dione, the CAS accession number is 118-48-9, molecular formula is C8H5NO3, and relative molecular weight is 163.13, and structural formula is shown in (I):
Isatoic anhydride can react with electrophilic reagent, can react with nucleophilic reagent again, and be a kind of useful chemical intermediate, be widely used in the synthetic of fine chemical products such as agrochemicals, dyestuff, pigment, spices, essence, medicine, whipping agent, fire retardant.
Prior art discloses the synthetic method of multiple isatoic anhydride, as anthranilic acid being dissolved in hot water and the concentrated hydrochloric acid, feeding phosgene and can produce isatoic anhydride; Perhaps phthalic imidine and clorox generation oxidizing reaction obtain isatoic anhydride; Be that raw material reaction prepares isatoic anhydride etc. perhaps with Tetra hydro Phthalic anhydride and triazo-compound.Wherein, anthranilic acid and phosgene reaction generate isatoic anhydride method because simple and easy to do, be swift in response and the most commonly used, phosgene is fed in the hot water and concentrated hydrochloric acid solution of anthranilic acid, can separate out isatoic anhydride.But molecular formula is COCl
2Phosgene be highly toxic substance, have strong and stimulating and asphyxiating, be the strict control reaction conditions of feedstock production isatoic anhydride with the phosgene, in order to avoid phosgene is overflowed human body is damaged.In addition, need to use excessive anthranilic acid in preparation process so that phosgene reaction is complete, therefore, the isatoic anhydride that obtains contains a large amount of anthranilic acids, and purity is lower.
At present, the domestic isatoic anhydride route synthetic herbicide bentazone that generally adopts may further comprise the steps: synthetic isatoic anhydride; Amidate action takes place and generates intermediate N sec.-propyl-2-aminobenzamide in isatoic anhydride and Isopropylamine in organic solvent; Described N-sec.-propyl-2-aminobenzamide and chlorsulfonic acid, 2-picoline generation sulfonation reaction form double salt; Described double salt is synthetic bentazone under the effect of phosphorus oxychloride.But, because isatoic anhydride is generally synthetic in water medium, need increase operation steps with could in organic solvent, carrying out amidate action after isatoic anhydride extraction, purifying, the drying, prolonged the production cycle.And existing isatoic anhydride product purity is lower, impurity such as the anthranilic acid that contains also are present in intermediate N sec.-propyl-2-aminobenzamide and the finished product bentazone, cause bentazone quality of the pharmaceutical preparations instability, turbid phenomenon be precipitated, be taken place to long-term the placement can generation.
Summary of the invention
In view of this, technical problem to be solved by this invention is to provide a kind of synthetic method of isatoic anhydride and the synthetic method of N-sec.-propyl-2-aminobenzamide, and is higher by the isatoic anhydride productive rate that method provided by the invention obtains, purity is higher; The synthetic method operation steps of N-sec.-propyl provided by the invention-2-aminobenzamide is simple, and the production cycle is shorter.
The invention provides a kind of synthetic method of isatoic anhydride, comprising:
Drip two (trichloromethyl) carbonate solution in the o-amino benzoyl acid solution, back flow reaction obtains isatoic anhydride.
Preferably, the rate of addition of described two (trichloromethyl) carbonate solution is 0.05gL
-1h
-1～0.5gL
-1h
-1
Preferably, the mol ratio of described two (trichloromethyl) carbonic ethers and described anthranilic acid is 0.34～0.40: 1.
The present invention also provides the synthetic method of a kind of N-sec.-propyl-2-aminobenzamide, comprising:
A), in the o-amino benzoyl acid solution, drip two (trichloromethyl) carbonate solution, back flow reaction obtains isatoic anhydride solution;
B), in described isatoic anhydride solution, drip Isopropylamine, reaction obtains N-sec.-propyl-2-aminobenzamide.
Preferably, the rate of addition of described two (trichloromethyl) carbonate solution is 0.05gL
-1h
-1～0.5gL
-1h
-1
Preferably, the mol ratio of described two (trichloromethyl) carbonic ethers and described anthranilic acid is 0.34～0.40: 1.
Preferably, in the described step a), the temperature of described back flow reaction is 60 ℃～90 ℃.
Preferably, the mol ratio of described Isopropylamine and described anthranilic acid is 1.0～1.5: 1.
Preferably, in the described step b), the temperature of described reaction is 50 ℃～65 ℃.
Preferably, described two (trichloromethyl) carbonate solution is the toluene solution of benzole soln or two (trichloromethyl) carbonic ether of dichloroethane solution, two (trichloromethyl) carbonic ether of dichloromethane solution, two (trichloromethyl) carbonic ether of chloroformic solution, two (trichloromethyl) carbonic ether of two (trichloromethyl) carbonic ether.
Compared with prior art, the present invention is that raw material reaction prepares isatoic anhydride with anthranilic acid and two (trichloromethyl) carbonic ether.Two (trichloromethyl) carbonic ether is a solid matter, can be in organic solvent medium and the anthranilic acid generation isatoic anhydride that reacts, and this reaction is homogeneous reaction, productive rate is higher; And two (trichloromethyl) carbonate reaction amount is controlled relatively, need not to add excessive anthranilic acid, and therefore the isatoic anhydride purity that obtains is higher.In addition, compare with phosgene, two (trichloromethyl) carbonic ether toxicity is lower, and transportation, storage and use are all safer, make that building-up process comparatively cleans, toxicity is lower, can not damage human body.
After anthranilic acid and two (trichloromethyl) carbonic ether reacts in organic solvent and generates isatoic anhydride, need not to described isatoic anhydride extract, operation such as purifying, drying can directly add Isopropylamine and carry out amidation and obtain N-sec.-propyl-2-aminobenzamide, be that raw material can " one kettle way " be produced N-sec.-propyl-2-aminobenzamide promptly with anthranilic acid and two (trichloromethyl) carbonic ether, reduced operation steps, shorten the production cycle, be easy to realize suitability for industrialized production.In addition,, can not influence the N-sec.-propyl-2-aminobenzamide and the finished product bentazone of subsequent preparation, make the bentazone steady quality that obtains because the isatoic anhydride purity that obtains is higher.
Description of drawings
The liquid chromatogram of N-sec.-propyl-2-aminobenzamide that Fig. 1 provides for the embodiment of the invention.
Embodiment
The invention provides a kind of synthetic method of isatoic anhydride, comprising:
Drip two (trichloromethyl) carbonate solution in the o-amino benzoyl acid solution, back flow reaction obtains isatoic anhydride.
The present invention is a raw material with anthranilic acid and two (trichloromethyl) carbonic ether, and the generation isatoic anhydride reacts in organic solvent.
Anthranilic acid has formula (II) structure, and is comparatively close with the isatoic anhydride structure with formula (I) structure.
Two (trichloromethyl) carbonic ether has another name called solid phosgene or triphosgene, and chemical formula is C
3O
3Cl
6, toxicity is lower, and is safer in transportation, storage and use.
According to the present invention, at first prepare o-amino benzoyl acid solution and two (trichloromethyl) carbonate solution, specifically may further comprise the steps:
Anthranilic acid is mixed with organic solvent, after intensification is stirred to dissolving, obtain the o-amino benzoyl acid solution;
Two (trichloromethyl) carbonic ether is dissolved in the organic solvent, obtains two (trichloromethyl) carbonate solution.
According to the present invention, the concentration of described o-amino benzoyl acid solution is preferably 0.05g/L～0.5g/L, and more preferably 0.1g/L～0.4g/L most preferably is 0.15g/L～0.3g/L; The concentration of described two (trichloromethyl) carbonate solution is preferably 0.2g/L～0.7g/L, and more preferably 0.3g/L～0.6g/L most preferably is 0.4g/L～0.5g/L.
Described organic solvent is preferably chloroform, methylene dichloride, ethylene dichloride, benzene or toluene, and more preferably methylene dichloride or ethylene dichloride most preferably are ethylene dichloride.
Reaction is more abundant in order to make, contain few impurity of trying one's best in the product that obtains, and the present invention is added drop-wise to two (trichloromethyl) carbonate solution in the o-amino benzoyl acid solution.In the present invention, the rate of addition of described two (trichloromethyl) carbonate solution should be tried one's best slowly, so that two (trichloromethyl) carbonic ethers and anthranilic acid fully react; But rate of addition is crossed slowly and can be extended manufacture cycle, and is unfavorable for suitability for industrialized production, and therefore, the rate of addition of described two (trichloromethyl) carbonate solution is preferably 0.05gL
-1h
-1～0.5gL
-1h
-1, 0.1gL more preferably
-1h
-1～0.4gL
-1h
-1, most preferably be 0.2gL
-1h
-1～0.3gL
-1h
-1
In the process that drips, anthranilic acid and two (trichloromethyl) carbonic ether reacts in organic solvent, and by obtaining isatoic anhydride behind addition condensation, the closed loop dehydrochlorination, reaction formula is as follows:
But, owing to contain three COCl groups in two (trichloromethyl) carbonic ether, in the dropping process, can not react completely, in order to make reaction more complete, obtain the higher isatoic anhydride of purity, proceed back flow reaction after two (trichloromethyl) carbonate solution dropwises, anthranilic acid and two (trichloromethyl) carbonic ether continues to take place the reaction of addition condensation, closed loop dehydrochlorination.
In the back flow reaction process of two (trichloromethyl) carbonic ethers and anthranilic acid, the control in reflux temperature and reaction times is significant to the productive rate and the purity of isatoic anhydride: temperature is crossed when hanging down, HCl is difficult to overflow, carry out thereby influence successful reaction, make that reaction yield is low, product purity is low; And temperature is too high, and isatoic anhydride can decompose and take place other side reactions, and producing by product influences its purity, reduces its productive rate.In the present invention, the temperature of described back flow reaction is preferably 50 ℃～100 ℃, more preferably 60 ℃～90 ℃, most preferably is 70 ℃～80 ℃.For the time of back flow reaction, the time is too short, and two (trichloromethyl) carbonic ethers and o-amino benzoyl acid-respons are incomplete, and the productive rate of isatoic anhydride and purity are all lower; And overlong time, isatoic anhydride can decompose and take place other side reactions, influences productive rate and purity.In the present invention, the time of described back flow reaction is preferably more than the 2h, and more preferably 3h～10h most preferably is 3h～5h.
The present invention is a raw material with two (trichloromethyl) carbonic ether, the reacting weight of itself and anthranilic acid is controlled, therefore the present invention preferably is controlled at the mol ratio of two (trichloromethyl) carbonic ethers and anthranilic acid within the zone of reasonableness, avoids the excessive degree of purity of production that influences of raw material.In the present invention, the mol ratio of described two (trichloromethyl) carbonic ethers and described anthranilic acid is preferably 0.34～0.40: 1, more preferably 0.35～0.38.
Need to prove that described reflux temperature and reflux time can be adjusted according to the addition of reaction raw materials and the concentration of reaction raw materials, so that obtain best productive rate and purity.These adjustment need not to pay creative work to those skilled in the art, therefore, also fall within protection scope of the present invention.
Compare with phosgene, not only toxicity is lower for two (trichloromethyl) carbonic ether, and can be dissolved in the organic solvent and react with anthranilic acid, because reacting weight is controlled relatively, need not to add excessive anthranilic acid, therefore can access productive rate, the higher isatoic anhydride of purity.Experiment shows, adopts method synthetic isatoic anhydride purity provided by the invention can reach 99.1%, and yield can reach 96.5%.In addition, because described isatoic anhydride generates at organic solvent medium, need not promptly to can be used as intermediate and other raw material reactions prepare fine chemical products such as agrochemicals, dyestuff through processing such as extractions, purification, drying, generate N-sec.-propyl-2-aminobenzamide as continuing to react, realize " one kettle way " production N-sec.-propyl-2-aminobenzamide with Isopropylamine.
According to the present invention, after anthranilic acid and two (trichloromethyl) carbonic ether generates isatoic anhydride, need not isatoic anhydride is purified, react but directly in described isatoic anhydride solution, drip Isopropylamine, can obtain N-sec.-propyl-2-aminobenzamide, react as follows:
According to the present invention, the mol ratio of described Isopropylamine and described anthranilic acid is preferably 1.0～1.5: 1, more preferably 1.1～1.4: 1.The temperature that described Isopropylamine and described anthranilic acid react is preferably 50 ℃～65 ℃, more preferably 55 ℃～60 ℃.; Reaction times is preferably more than the 2h, and more preferably 3h～10h most preferably is 3h～5h.
In order to make reaction more abundant, the present invention is added drop-wise to described Isopropylamine in the described anthranilic acid, is preferably more than the 2h to dropwise.The dropping time of described Isopropylamine is relevant with the consumption of described Isopropylamine, consumption more for a long time, rate of addition can be fast slightly; Consumption hour, rate of addition can be slow slightly, those skilled in the art can carry out the adjustment of rate of addition as the case may be; In addition, those skilled in the art also can adjust the rate of addition of Isopropylamine according to the production cycle of N-sec.-propyl-2-aminobenzamide.
N-sec.-propyl-2-aminobenzamide is an intermediate of producing the weedicide bentazone, obtains can proceeding the synthetic of bentazone after N-sec.-propyl-2-aminobenzamide.
After anthranilic acid and two (trichloromethyl) carbonic ether reacts in organic solvent and generates isatoic anhydride, need not to described isatoic anhydride extract, operation such as purifying, drying can directly add Isopropylamine and carry out amidation and obtain N-sec.-propyl-2-aminobenzamide, be that raw material can " one kettle way " be produced N-sec.-propyl-2-aminobenzamide promptly with anthranilic acid and two (trichloromethyl) carbonic ether, reduced operation steps, shorten the production cycle, be easy to realize suitability for industrialized production.In addition,, can not influence the N-sec.-propyl-2-aminobenzamide and the finished product bentazone of subsequent preparation, make the bentazone steady quality that obtains because the isatoic anhydride purity that obtains is higher.Experiment shows that the purity that adopts method provided by the invention to synthesize N-sec.-propyl-2-aminobenzamide can reach 99.3%, and yield can reach more than 90%.
In order to further specify the present invention, the synthetic method of isatoic anhydride provided by the invention and the synthetic method of N-sec.-propyl-2-aminobenzamide are described in detail below in conjunction with embodiment.
In the 500mL four-hole bottle that agitator, thermometer and circulating condensing device are housed, add 20g commercially available, purity is 98% anthranilic acid and 150mL ethylene dichloride, turn on agitator and circulating condensing device, be warming up to 68 ℃, be stirred to anthranilic acid and dissolve fully, obtain the o-amino benzoyl acid solution; Two (trichloromethyl) carbonic ether that 16g is commercially available is dissolved in the 40mL ethylene dichloride, obtains two (trichloromethyl) carbonate solution; Described two (trichloromethyl) carbonate solution is slowly dropped in the described o-amino benzoyl acid solution, and 2h drips off, and is warming up to 75 ℃ of back flow reaction 2h then, obtains isatoic anhydride solution.After reducing to room temperature,, be weighed as 22.7g after the drying with described isatoic anhydride solution suction filtration.Described dry thing is carried out liquid chromatogram measuring, and wherein isatoic anhydride content is 99.1%, and yield is 96.5%.
In the 500mL four-hole bottle that agitator, thermometer and circulating condensing device are housed, add 20g commercially available, purity is 98% anthranilic acid and 150mL ethylene dichloride, turn on agitator and circulating condensing device, be warming up to 68 ℃, be stirred to anthranilic acid and dissolve fully, obtain the o-amino benzoyl acid solution; Two (trichloromethyl) carbonic ether that 16g is commercially available is dissolved in the 40mL ethylene dichloride, obtains two (trichloromethyl) carbonate solution; Described two (trichloromethyl) carbonate solution is slowly dropped in the described o-amino benzoyl acid solution, and 2h drips off, and is warming up to 80 ℃ of back flow reaction 2h then, obtains isatoic anhydride solution;
Described isatoic anhydride solution is cooled to 55 ℃, slowly drip the 12g Isopropylamine, 2h drips off, then insulation reaction 1h, obtain N-sec.-propyl-2-aminobenzoyl amine aqueous solution, with described solution suction filtration, in the suction filtration thing, add 150mL water, after removing ethylene dichloride, intensification reduces to room temperature, suction filtration once more, 65 ℃ of oven dry with weighing dry substances, are 23.5g.Described dry thing is carried out liquid chromatogram measuring, the results are shown in Figure 1 and table 1, the analytical results table of the liquid chromatography of N-sec.-propyl-2-aminobenzamide that the liquid chromatogram of N-sec.-propyl-2-aminobenzamide that Fig. 1 provides for the embodiment of the invention, table 1 provide for the embodiment of the invention.
The analytical results of the liquid chromatography of N-sec.-propyl-2-aminobenzamide that table 1 embodiment of the invention provides
By Fig. 1 and table 1 as can be known, the content of N-sec.-propyl-2-aminobenzamide is 99.3%, and yield is 91%.
In the 500mL four-hole bottle that agitator, thermometer and circulating condensing device are housed, add 20g commercially available, purity is 98% anthranilic acid and 150mL ethylene dichloride, turn on agitator and circulating condensing device, be warming up to 68 ℃, be stirred to anthranilic acid and dissolve fully, obtain the o-amino benzoyl acid solution; Two (trichloromethyl) carbonic ether that 17g is commercially available is dissolved in the 40mL ethylene dichloride, obtains two (trichloromethyl) carbonate solution; Described two (trichloromethyl) carbonate solution is slowly dropped in the described o-amino benzoyl acid solution, and 2h drips off, and is warming up to 70 ℃ of back flow reaction 2h then, obtains isatoic anhydride solution;
Described isatoic anhydride solution is cooled to 55 ℃, slowly drip the 12.5g Isopropylamine, 2h drips off, then insulation reaction 1h, obtain N-sec.-propyl-2-aminobenzoyl amine aqueous solution, with described solution suction filtration, in the suction filtration thing, add 150mL water, after removing ethylene dichloride, intensification reduces to room temperature, suction filtration once more, 65 ℃ of oven dry with weighing dry substances, are 23.3g.Described dry thing is carried out liquid chromatogram measuring, and wherein, the content of N-sec.-propyl-2-aminobenzamide is 99.3%, and yield is 90.9%.
Embodiment 4
In the 5000L reactor, add 200kg commercially available, purity is 98% anthranilic acid and 1500L ethylene dichloride, stirs to be warming up to 70 ℃ anthranilic acid is dissolved fully, obtains the o-amino benzoyl acid solution; Two (trichloromethyl) carbonic ether that 170kg is commercially available is dissolved in the 400L ethylene dichloride, obtains two (trichloromethyl) carbonate solution; Described two (trichloromethyl) carbonate solution is slowly dropped in the described o-amino benzoyl acid solution, and 2h drips off, and is warming up to 85 ℃ of back flow reaction 2h then, obtains isatoic anhydride solution;
Described isatoic anhydride solution is cooled to 53 ℃, slowly drip the 125kg Isopropylamine, 3h drips off, then insulation reaction 2h, obtain N-sec.-propyl-2-aminobenzoyl amine aqueous solution, with described solution suction filtration, in the suction filtration thing, add 150mL water, after removing ethylene dichloride, intensification reduces to room temperature, suction filtration once more, 65 ℃ of oven dry with weighing dry substances, are 23.3g.Described dry thing is carried out liquid chromatogram measuring, and wherein, the content of N-sec.-propyl-2-aminobenzamide is 99.3%, and yield is 90.7%.
The explanation of above embodiment just is used for helping to understand method of the present invention and core concept thereof.Should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention, can also carry out some improvement and modification to the present invention, these improvement and modification also fall in the protection domain of claim of the present invention.
Claims (4)
1. the synthetic method of N-sec.-propyl-2-aminobenzamide comprises:
A), in the o-amino benzoyl acid solution, drip two (trichloromethyl) carbonate solution, back flow reaction obtains isatoic anhydride solution, described o-amino benzoyl acid solution is that anthranilic acid is dissolved in the solution that organic solvent obtains, and described two (trichloromethyl) carbonate solution is that two (trichloromethyl) carbonic ether is dissolved in the solution that organic solvent obtains; The rate of addition of described two (trichloromethyl) carbonate solution is 0.05gL
-1h
-1～0.5gL
-1h
-1The temperature of described back flow reaction is 60 ℃～90 ℃;
B), in described isatoic anhydride solution, drip Isopropylamine, reaction obtains N-sec.-propyl-2-aminobenzamide, and the temperature of described reaction is 50 ℃～65 ℃.
2. synthetic method according to claim 1 is characterized in that, the mol ratio of described two (trichloromethyl) carbonic ethers and described anthranilic acid is 0.34～0.40:1.
3. synthetic method according to claim 1 is characterized in that, the mol ratio of described Isopropylamine and described anthranilic acid is 1.0～1.5:1.
4. synthetic method according to claim 1, it is characterized in that described two (trichloromethyl) carbonate solution is the toluene solution of benzole soln or two (trichloromethyl) carbonic ether of dichloroethane solution, two (trichloromethyl) carbonic ether of dichloromethane solution, two (trichloromethyl) carbonic ether of chloroformic solution, two (trichloromethyl) carbonic ether of two (trichloromethyl) carbonic ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010297432 CN101973956B (en) | 2010-09-26 | 2010-09-26 | Methods for synthesizing isatoic anhydride and N-isopropyl-2-aminobenzamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010297432 CN101973956B (en) | 2010-09-26 | 2010-09-26 | Methods for synthesizing isatoic anhydride and N-isopropyl-2-aminobenzamide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101973956A CN101973956A (en) | 2011-02-16 |
| CN101973956B true CN101973956B (en) | 2013-07-31 |
Family
ID=43573874
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010297432 Active CN101973956B (en) | 2010-09-26 | 2010-09-26 | Methods for synthesizing isatoic anhydride and N-isopropyl-2-aminobenzamide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101973956B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102863399B (en) * | 2012-10-09 | 2014-10-22 | 西北大学 | Synthetic method for isatoic anhydride derivative |
| CN103450107B (en) * | 2013-09-13 | 2016-05-25 | 陕西嘉禾生物科技股份有限公司 | A kind of preparation method of N-methyl-isatin acid anhydrides |
| CN108586362A (en) * | 2018-07-09 | 2018-09-28 | 郭秦 | A kind of dichloro- pyrazole amide intermediate synthetic method |
| CN114674946A (en) * | 2022-03-12 | 2022-06-28 | 青岛科技大学 | Method for determining four main components in N-isopropyl-anthranilamide synthesis reaction liquid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008092049A1 (en) * | 2007-01-26 | 2008-07-31 | Smithkline Beecham Corporation | Anthranilamide inhibitors of aurora kinase |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1063688A (en) * | 1991-01-28 | 1992-08-19 | 南开大学 | The synthetic method of Bentazon herbicide |
-
2010
- 2010-09-26 CN CN 201010297432 patent/CN101973956B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008092049A1 (en) * | 2007-01-26 | 2008-07-31 | Smithkline Beecham Corporation | Anthranilamide inhibitors of aurora kinase |
Non-Patent Citations (1)
| Title |
|---|
| Huang, Jun-Min et al.An unusual addition and ring-closure reaction of 1-(2-bromoethyl)-2,3-dihydro-3-propyl-1,3,2-benzo- diazaphosphorin-4(1H)- one 2-oxide with carbon disulfide for a new and convenient synthesis of the fused phosphorus heterocyclic compound.《Synthetic Communications》.2002,第132卷(第14期),2215-2225. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101973956A (en) | 2011-02-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108689876B (en) | Preparation method of sodium 8- (2-hydroxybenzamido) caprylate | |
| CN101973956B (en) | Methods for synthesizing isatoic anhydride and N-isopropyl-2-aminobenzamide | |
| CN105061416B (en) | A kind of method for preparing flumioxazin | |
| CN102775358B (en) | Preparation method of 6-fluoro-3-hydroxy-2-pyrazinamide | |
| CN104961710A (en) | Synthesis method of dinotefuran | |
| CN107141278A (en) | The method that bicyclic alcohols are prepared using DDB | |
| CN106946956A (en) | A kind of recrystallization method of acetic acid esters of sucrose 6 and its application | |
| CN103724258A (en) | Preparation method of sorafenib | |
| CN104961724B (en) | A kind of vanguard technology for obtaining high-purity Desloratadine | |
| CN109265341B (en) | Synthetic method of 5-aminolevulinic acid hydrochloride | |
| CN104402813B (en) | Novel method for synthesizing sorafenib | |
| CN106631885A (en) | 4-formaldoxime benzoate derivative preparation method | |
| CN106187870A (en) | A kind of 4 picoline location nitrations are the method for 3 nitro 4 picolines | |
| CN101735165A (en) | Preparation method of 3-morpholone | |
| CN107417606B (en) | Method for converting N-cyanomethyl bis (trifluoromethyl) nicotinamide into flonicamid and application | |
| CN103159694A (en) | Continuous isatoic anhydride production method | |
| CN103193666A (en) | Preparation method of 2-amino-3-chlorobenzoic methyl ester | |
| CN110563721A (en) | Preparation method of azasetron hydrochloride | |
| CN102432559A (en) | Synthetic method for preparing 2,6-dichlorobenzoxazole by photocuring | |
| CN101906115B (en) | Preparation method of beta-methyl carbapenem antibiotic intermediate | |
| CN101391969A (en) | Method for preparing N-methyl-2-(2,4-dichlorophenoxy) acetamide | |
| CN115677593B (en) | Preparation method of terglazan intermediate | |
| CN104292133A (en) | Method for synthesizing anti-cancer drug vorinostat | |
| CN108276328A (en) | A kind of preparation method of Sorafenib | |
| CN103864632B (en) | Production method for glycine ethyl ester hydrochloride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |