CN110938015B - Preparation method of azido-substituted salicylic acid derivative - Google Patents

Preparation method of azido-substituted salicylic acid derivative Download PDF

Info

Publication number
CN110938015B
CN110938015B CN201911243788.8A CN201911243788A CN110938015B CN 110938015 B CN110938015 B CN 110938015B CN 201911243788 A CN201911243788 A CN 201911243788A CN 110938015 B CN110938015 B CN 110938015B
Authority
CN
China
Prior art keywords
salicylic acid
acid derivative
azido
substituted salicylic
azide
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
Application number
CN201911243788.8A
Other languages
Chinese (zh)
Other versions
CN110938015A (en
Inventor
孙斌
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chongqing Technology and Business University
Original Assignee
Chongqing Technology and Business University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Chongqing Technology and Business University filed Critical Chongqing Technology and Business University
Priority to CN201911243788.8A priority Critical patent/CN110938015B/en
Publication of CN110938015A publication Critical patent/CN110938015A/en
Application granted granted Critical
Publication of CN110938015B publication Critical patent/CN110938015B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C247/00—Compounds containing azido groups
    • C07C247/16—Compounds containing azido groups with azido groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C247/18—Compounds containing azido groups with azido groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention discloses a preparation method of an azido-substituted salicylic acid derivative, which comprises the steps of adding azide salt and the salicylic acid derivative into an alcohol-water mixed solvent at low temperature, adding simple substance bromine to react and precipitate solid, and filtering, washing and drying to obtain the azido-substituted salicylic acid derivative. The method has simple steps, low reagent cost and high reaction speed, is easy to obtain the azido-substituted salicylic acid derivative, has theoretical significance in methodology research, has wide application prospect, and can generate great economic benefit in industrial implementation.

Description

Preparation method of azido-substituted salicylic acid derivative
Technical Field
The invention belongs to the field of chemical medicine, and particularly relates to a preparation method of an azido-substituted salicylic acid derivative.
Background
At present, in the chemical and medical industries, salicylic acid is mainly used as a raw material in the pharmaceutical industry, and the salicylic acid derivatives found at present have wide application in the aspects of medicines and dyes, such as aspirin, sodium salicylate, salicylamide, analgesic, phenyl salicylate, blood defense-67 and the like which are common medicines in the medical field at present; in the dye industry, salicylic acid is used for preparing mordant pure yellow, direct brown 3GN, acid chrome yellow and other dyes; in addition, salicylic acid can also be used as a rubber vulcanization retardant, a disinfecting preservative, and the like. Therefore, if salicylic acid or a derivative thereof is modified with a new functional group, it is possible to obtain a new pharmaceutical, agrochemical and other fine chemicals. In the prior art, because azido is a strong electron-withdrawing group and can change certain properties of salicylic acid or derivatives thereof after being introduced into salicylic acid or derivatives thereof, azido can react with carbon-carbon triple bonds to introduce other functional groups into salicylic acid, and in addition, azido can be reduced into amino which is an active group, and a plurality of functional groups can be introduced into salicylic acid and derivatives thereof through the amino, so that azido has great utilization value for preparing salicylic acid derivatives.
There are two common methods currently used to introduce azido groups into salicylic acid and its derivatives:
method 1. Catalytic process: iodo salicylic acid or its derivative is obtained, and then reacted with sodium azide at high temperature in the presence of cuprous salt such as cuprous iodide to obtain salicylic acid and its derivative containing azido group. The method has the defects of expensive reagent (such as iodine), high reaction temperature, long reaction time, difficult removal of solvent after the reaction is finished and the like, so that the method can only be researched as methodology research, cannot realize industrial production and has no economy.
Method 2 diazonium salt method: 5-aminosalicylic acid is used as a raw material, diazonium salt is prepared in the presence of sodium nitrite in sulfuric acid rain, and the diazonium salt reacts with sodium azide to obtain the 5-azidosalicylic acid. Although this method does not require expensive reagents and high-temperature long-time screening, it requires at least nitrification and reduction, and the production cost of the product is relatively high, and there is a considerable risk if industrialization is carried out.
Therefore, the method for preparing the azido-substituted salicylic acid and the derivative thereof, which has the advantages of simple steps, low reagent cost, high reaction speed and easy product obtaining, has a theoretical significance on methodology research, has a wide application prospect, and realizes industrial implementation to generate great economic benefits.
Disclosure of Invention
The invention aims to overcome the defects that the cost for preparing azido-substituted salicylic acid or derivatives thereof is higher and the widespread application and implementation are not facilitated in the prior art, and provides a preparation method of azido-substituted salicylic acid derivatives, which has the advantages of simple steps, low reagent cost, high reaction speed and easiness in widespread implementation.
The invention adopts the following technical scheme:
the key point of the preparation method of the azido-substituted salicylic acid derivative is that: under a low-temperature environment, adding azide salt and a salicylic acid derivative into an alcohol-water mixed solvent, adding simple substance bromine, reacting to precipitate solid, and filtering, washing and drying to obtain the azide-substituted salicylic acid derivative.
As a preferred scheme, the low-temperature environment is 0-5 ℃.
Preferably, the preparation method comprises the following specific preparation steps:
s1, mixing azide salt and a small amount of water, and then adding a proper amount of methanol to obtain a mixture, wherein sodium azide is not separated out;
s2, adding a proper amount of salicylic acid derivative into the mixed solution obtained in the step S1, fully dissolving, and controlling the environmental temperature to be kept at 0-5 ℃;
s3, keeping the temperature unchanged, stirring the mixed solution obtained in the step S2, slowly adding a proper amount of elemental bromine while stirring, and continuously stirring for 30min after the elemental bromine is added;
and S4, pouring the mixture obtained in the step S3 into a proper amount of ice water, stirring, and filtering, washing and drying after a large amount of solids are separated out to obtain the azido-substituted salicylic acid derivative.
Preferably, sodium azide is adopted as the azide salt, and the molar ratio of the sodium azide to the salicylic acid derivative is 4:1.
preferably, the molar ratio of the elemental bromine to the azide salt is 1:2.
preferably, the step S1 ensures that the sodium azide does not precipitate by controlling the amount of methanol added.
Preferably, the salicylic acid derivative is methyl salicylate or methyl 3-methyl salicylate.
As a preferred scheme, the azido-substituted salicylic acid derivative is obtained as a crude product after filtration, washing and drying, and then the crude product is recrystallized by ethyl acetate to obtain a finished product with higher purity.
Has the beneficial effects that: the preparation method of the azido-substituted salicylic acid derivative has the advantages of simple steps, low reagent cost, high reaction speed and easy obtainment of the azido-substituted salicylic acid derivative, has theoretical significance on methodology research, has wide application prospect, and can produce great economic benefit in industrial implementation.
Drawings
FIG. 1 is a schematic flow diagram of the process of the present invention;
FIG. 2 shows the product C prepared in example 1 and example 2 9 H 10 N 3 O 3 Using CDCl 3 As a solvent, a nuclear magnetic resonance hydrogen spectrum with the frequency of radio frequency electromagnetic wave of 400 MHZ;
FIG. 3 shows the product C prepared in example 1 and example 2 9 H 10 N 3 O 3 Using CDCl 3 As a solvent, a nuclear magnetic resonance carbon spectrogram with the frequency of radio frequency electromagnetic waves of 100 MHZ;
FIG. 4 shows product C prepared in example 3 and example 4 8 H 7 N 6 O 3 Using DMSO-d 6 As a solvent, a nuclear magnetic resonance hydrogen spectrogram with the frequency of radio frequency electromagnetic waves of 400 MHZ;
FIG. 5 shows product C prepared in example 3 and example 4 8 H 7 N 6 O 3 Using DMSO-d 6 As a solvent, a nuclear magnetic resonance carbon spectrum with the frequency of radio frequency electromagnetic wave of 100 MHZ;
FIG. 6 shows product C prepared in example 1 and example 2 9 H 10 N 3 O 3 The molecular structural formula of (1);
FIG. 7 shows the product C prepared in example 1 and example 2 8 H 7 N 6 O 3 The molecular structural formula of (1).
Detailed Description
The invention is described in further detail below with reference to the accompanying drawings:
the invention discloses a preparation method of azido-substituted salicylic acid derivatives, which comprises the steps of adding azide salt and salicylic acid derivatives into an alcohol-water mixed solvent under a low-temperature environment, adding simple substance bromine for reaction to precipitate solids, and filtering, washing and drying to obtain the azido-substituted salicylic acid derivatives.
As shown in the attached figure 1, when the preparation of the azido-substituted salicylic acid derivative is specifically carried out, the following steps are mainly adopted:
s1, mixing azide salt and a small amount of water, adding a proper amount of methanol to obtain a mixture, and controlling the amount of the added methanol to ensure that no sodium azide is separated out;
s2, adding a proper amount of salicylic acid derivative into the mixed solution obtained in the step S1, fully dissolving, and controlling the environmental temperature to be kept at 0-5 ℃;
s3, keeping the temperature unchanged, stirring the mixed solution obtained in the step S2, slowly adding a proper amount of elemental bromine while stirring, and continuously stirring for 30min after the elemental bromine is added;
and S4, pouring the mixture obtained in the step S3 into a proper amount of ice water, stirring, and filtering, washing and drying after a large amount of solids are precipitated to obtain the azido-substituted salicylic acid derivative.
When the preparation of the azido-substituted salicylic acid derivative is carried out by the steps, sodium azide is used as the azide salt, and the molar ratio of the sodium azide to the salicylic acid derivative is 4:1; the salicylic acid derivative can adopt methyl salicylate or 3-methyl salicylate; the molar ratio of the elemental bromine to the azide salt is 1:2.
after a large amount of solid products are separated out in the step S4, excess sodium sulfite is used for neutralizing unreacted elemental bromine, then the filtering operation is carried out, a filter cake obtained by filtering is washed by ice water for 3 times, then the vacuum drying is carried out to obtain a crude product of the azido-substituted salicylic acid derivative, and the crude product is recrystallized by ethyl acetate to obtain a product with the purity of more than 99 percent.
From the analysis of the prior art, the pseudohalogen compounds can obtain the pseudohalogen aromatic compounds by synthesizing azido-substituted salicylic acid derivatives, but a large number of experiments show that if the method is adopted, sodium azide reacts with the salicylic acid derivatives, and bromine substitution products are obtained no matter how conditions are changed, because the sodium azide easily generates hydrogen azide in formic acid and acetic acid environment and volatilizes. To solve this problem, we finally determined a certain ratio of methanol-water solvent to ensure that the resulting product is azido substituted rather than bromo. When judging whether the product is the azido-substituted product, the best method is to characterize the product by infrared spectrum, nuclear magnetic resonance hydrogen spectrum and mass spectrum, wherein the infrared spectrum is important and can directly reflect whether the product is azido-substituted or bromine-substituted according to the characteristic absorption peak of azido groups, and the product prepared by the method is the azido-substituted salicylic acid derivative which is specifically proved by combining with the embodiment 1-4.
Example 1: methyl 3-methylsalicylate (3.32g, 20mmol) and sodium azide (5.2g, 80mmol) were dissolved in a methanol-water mixed solvent (26 mL) in a 50mL three-necked flask equipped with a mechanical stirrer and a constant-pressure dropping funnel, and then the reaction flask was cooled with ice water, stirred at a low temperature of 0 to 5 ℃ for 2 to 3 hours, and elemental bromine (2.1mL, 40mmol) was slowly added dropwise with stirring. In the process of dropwise adding the elemental bromine, a large amount of solid is generated, after dropwise adding, stirring is continuously carried out for 30min at the temperature, the reaction mixture is poured into 50mL of ice water, filtering is carried out after stirring is carried out for 5min, a filter cake is mixed with 50mL of water, residual acid is neutralized by a saturated sodium bicarbonate solution and a sodium sulfite solution, filtering is carried out, the filter cake is washed to be neutral by water, vacuum drying is carried out, a crude product is obtained, 3.5g of a product with the purity of more than 99% is obtained after the crude product is recrystallized by ethyl acetate, the yield is 84.1%, and the product is respectively subjected to nuclear magnetic resonance hydrogen spectrum analysis, nuclear magnetic resonance carbon spectrum analysis, infrared spectrum analysis and electrospray ionization mass spectrometry to obtain the following results:
1 H NMR(400MHz,CDC l3 ,ppm)δ10.93(s,1H,OH),7.79(d,J＝2.0Hz,1H),3.93(s,3H,OCH3),2.23(s,3H,ArCH3)；
13 C NMR(100MHz,CDC l3 ,ppm)δ169.9,159.1,138.8,129.5,129.2,110.1,52.5,15.5；
IR (KBr) upsilon: 2116 (expansion and contraction vibration frequency of N3);
ESI-MS Calcd for C 9 H 10 N 3 O 3 [M+H]+208.07,Found:208.06。
example 2: methyl 3-methylsalicylate (33.2 g,0.2 mol) and sodium azide (52.0 g,0.8 mol) were dissolved in a methanol-water mixed solvent (260 mL) in a 500mL three-necked flask equipped with a mechanical stirrer and a constant pressure dropping funnel, and then the reaction flask was cooled with ice water and stirred at a low temperature of 0 to 5 ℃ for 2 to 3 hours while slowly dropping elemental bromine (20.5 mL,0.4 mol) under stirring. In the process of dropwise adding the elemental bromine, a large amount of solid is generated, after dropwise adding, stirring is continuously carried out for 30min at the temperature, the reaction mixture is poured into 500mL of ice water, filtering is carried out after stirring is carried out for 5min, a filter cake is mixed with 200mL of water, residual acid is neutralized by saturated sodium bicarbonate solution and sodium sulfite solution, filtering is carried out, the filter cake is washed to be neutral by water and dried in vacuum, a crude product is obtained, 34.8g of product with the purity of more than 99% is obtained after the crude product is recrystallized by ethyl acetate, the yield is 84%, and the product is respectively subjected to nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum, infrared spectrum and electrospray ionization mass spectrometry to obtain the following results:
1 H NMR(400MHz,CDC l3 ,ppm)δ10.93(s,1H,OH),7.79(d,J＝2.0Hz,1H),3.93(s,3H,OCH3),2.23(s,3H,ArCH3)；
13 C NMR(100MHz,CDC l3 ,ppm)δ169.9,159.1,138.8,129.5,129.2,110.1,52.5,15.5；
IR (KBr) upsilon: 2116 (expansion and contraction vibration frequency of N3);
ESI-MS Calcd for C 9 H 10 N 3 O 3 [M+H]+208.07,Found:208.06。
example 3: methyl salicylate (3.0 g, 20mmol) and sodium azide (5.2 g, 80mmol) were dissolved in a methanol-water mixed solvent (26 mL) in a 50mL three-necked flask equipped with a mechanical stirrer and a constant-pressure dropping funnel, and then the reaction flask was cooled with ice water, stirred at a low temperature of 0-5 ℃ for 2-3 hours, and elemental bromine (2.1mL, 40mmol) was slowly added dropwise with stirring. In the process of dropwise adding the elemental bromine, a large amount of solid is generated, after dropwise adding, stirring is continuously carried out for 30min at the temperature, the reaction mixture is poured into 50mL of ice water, filtering is carried out after stirring is carried out for 5min, a filter cake is mixed with 50mL of water, residual acid is neutralized by a saturated sodium bicarbonate solution and a sodium sulfite solution, filtering is carried out, the filter cake is washed to be neutral by water, vacuum drying is carried out, a crude product is obtained, 3.8g of a product with the purity of more than 99% is obtained after the crude product is recrystallized by ethyl acetate, the yield is 80.5%, and the product is respectively subjected to nuclear magnetic resonance hydrogen spectrum analysis, nuclear magnetic resonance carbon spectrum analysis, infrared spectrum analysis and electrospray ionization mass spectrometry to obtain the following results:
1 H NMR(400MHz,DMSO-d 6 ,ppm)δ11.06(s,1H,OH),8.06(s,1H),7.86(s,1H),3.90(s,3H)；
13 C NMR(100MHz,DMSO-d 6 ,ppm)δ168.1,156.2,140.5,131.9,116.3,112.8,110.8,53.7；
IR (KBr) upsilon: 2116 (expansion and contraction vibration frequency of N3);
ESI-MS Calcd for C 8 H 7 N 6 O 3 [M+H]+235.06,Found:235.05。
example 4: in a 500mL three-necked flask equipped with a mechanical stirrer and a constant pressure dropping funnel, methyl salicylate (30.4 g, 0.2mol) and sodium azide (52.0 g, 0.8mol) were dissolved in a methanol-water mixed solvent (260 mL), and then the reaction flask was cooled with ice water, stirred at a low temperature of 0 to 5 ℃ for 2 to 3 hours, and elemental bromine (20.5 mL, 0.4mol) was slowly added dropwise with stirring. In the process of dropwise adding the elemental bromine, a large amount of solid is generated, after the dropwise adding is finished, stirring is continuously carried out for 30min at the temperature, the reaction mixture is poured into 500mL of ice water, filtering is carried out after stirring for 5min, a filter cake is mixed with 200mL of water, residual acid is neutralized by a saturated sodium bicarbonate solution and a sodium sulfite solution, filtering is carried out, the filter cake is washed to be neutral by water, vacuum drying is carried out, a crude product is obtained, 37.5g of a product with the purity of more than 99 percent is obtained after the crude product is recrystallized by ethyl acetate, and the yield is 80 percent.
1 H NMR(400MHz,DMSO-d 6 ,ppm)δ11.06(s,1H,OH),8.06(s,1H),7.86(s,1H),3.90(s,3H)；
13 C NMR(100MHz,DMSO-d 6 ,ppm)δ168.1,156.2,140.5,131.9,116.3,112.8,110.8,53.7；
IR (KBr) v 2116 (N3 expansion and contraction vibration frequency);
ESI-MS Calcd for C 8 H 7 N 6 O 3 [M+H]+235.06,Found:235.05。
as shown in FIGS. 2 to 5, the products prepared in examples 1 to 4 were analyzed by hydrogen NMR, carbon NMR, IR and electrospray ionization mass spectrometry to find that the products prepared by the method were azido-substituted salicylic acid derivatives, and the products of examples 1 and 2 were C 9 H 10 N 3 O 3 The products of examples 3 and 4 are both C 8 H 7 N 6 O 3 。
Finally, it should be noted that the above-mentioned description is only a preferred embodiment of the present invention, and those skilled in the art can make various similar representations without departing from the spirit and scope of the present invention.

Claims (5)

1. A method for preparing an azido-substituted salicylic acid derivative, characterized in that: adding azide salt and salicylic acid derivatives into an alcohol-water mixed solvent at 0-5 ℃, adding simple substance bromine for reaction to separate out solid, and filtering, washing and drying to obtain azide-substituted salicylic acid derivatives;
the salicylic acid derivative adopts methyl salicylate or 3-methyl salicylate;
the preparation method comprises the following specific steps:
s1, mixing azide salt and a small amount of water, and then adding a proper amount of methanol to obtain a mixture, wherein sodium azide is not separated out;
s2, adding a proper amount of salicylic acid derivative into the mixed solution obtained in the step S1, fully dissolving, and controlling the environmental temperature to be kept at 0-5 ℃;
s3, keeping the temperature unchanged, stirring the mixed solution obtained in the step S2 for 2-3 hours, slowly adding a proper amount of elemental bromine while stirring, and continuously stirring for 30min after the elemental bromine is added;
and S4, pouring the mixture obtained in the step S3 into a proper amount of ice water, stirring, and after a large amount of solid is separated out, filtering, washing and drying to obtain the 5-azido substituted salicylic acid derivative.
2. The method of claim 1, wherein the azido-substituted salicylic acid derivative is prepared by: the azide salt is sodium azide, and the molar ratio of the sodium azide to the salicylic acid derivative is 4:1.
3. the method of claim 1, wherein the azido-substituted salicylic acid derivative is prepared by: the molar ratio of the elemental bromine to the azide salt is 1:2.
4. the method of claim 1, wherein the azido-substituted salicylic acid derivative is prepared by: the step S1 ensures that the sodium azide is not separated out by controlling the amount of the added methanol.
5. The method for producing an azido-substituted salicylic acid derivative according to any one of claims 1 to 4, characterized in that: filtering, washing and drying to obtain the azido-substituted salicylic acid derivative as a crude product, and recrystallizing the crude product with ethyl acetate to obtain a finished product with higher purity.
CN201911243788.8A 2019-12-06 2019-12-06 Preparation method of azido-substituted salicylic acid derivative Active CN110938015B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911243788.8A CN110938015B (en) 2019-12-06 2019-12-06 Preparation method of azido-substituted salicylic acid derivative

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201911243788.8A CN110938015B (en) 2019-12-06 2019-12-06 Preparation method of azido-substituted salicylic acid derivative

Publications (2)

Publication Number Publication Date
CN110938015A CN110938015A (en) 2020-03-31
CN110938015B true CN110938015B (en) 2022-10-25

Family

ID=69909140

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911243788.8A Active CN110938015B (en) 2019-12-06 2019-12-06 Preparation method of azido-substituted salicylic acid derivative

Country Status (1)

Country Link
CN (1) CN110938015B (en)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008151211A1 (en) * 2007-06-05 2008-12-11 Sanofi-Aventis Substituted benzoylamino-indan-2-carboxylic acids and related compounds
JP6700203B2 (en) * 2014-07-01 2020-05-27 レンペックス・ファーマシューティカルズ・インコーポレイテッド Boronic acid derivatives and their therapeutic use
WO2016149393A1 (en) * 2015-03-17 2016-09-22 Rempex Pharmaceuticals, Inc. Boronic acid derivatives and therapeutic uses thereof
TW201906616A (en) * 2017-07-06 2019-02-16 日商大日本住友製藥股份有限公司 Amide derivative

Also Published As

Publication number Publication date
CN110938015A (en) 2020-03-31

Similar Documents

Publication Publication Date Title
CN111704555B (en) Method for synthesizing 4-methoxy-2-nitroaniline by adopting continuous flow reactor
CN101891606A (en) New method for synthesizing rhodium caprylate (II)
CN113416150A (en) Novel synthesis method of lobaplatin intermediate
CN110938015B (en) Preparation method of azido-substituted salicylic acid derivative
CN110698352B (en) Synthetic method of 3-bromo-5-aminocatechol dimethyl ether
CN110627754B (en) Method for preparing 2-oxo-2-furyl acetic acid by using continuous flow microchannel reactor
CN106986886A (en) A kind of preparation method of the Trifluoromethoxyphen-l pinacol borate of 4 fluorine 3
CN107501338B (en) Preparation method of 2, 6-diaminopyridine condensed 4-carboxybenzaldehyde bis-Schiff base cobalt complex
CN106349163B (en) One kind being based on the metal organic coordination polymer and the preparation method and application thereof of Cu (I)
CN115557904A (en) Synthetic method suitable for large-scale production of 5, 7-bis (trifluoromethyl) quinazoline-2, 4-diketone
CN113801104B (en) Preparation method of hydrolysis impurity of ivermectin Mo Sida cyclic lactone
CN114644582A (en) Preparation method of phenyl bis-thiourea compound
CN110256325B (en) Process method for synthesizing 3,3' -diindolylmethane
CN105254485B (en) A kind of method of o-phenylenediamine condensing benzaldehyde Bis-Schiff Bases palladium complex catalyst synthesis difunisal
CN114149335A (en) Synthesis method of 4, 4' -diaminodiphenyl ether by taking parachloroaniline as initial raw material
CN108727445B (en) Synthesis method of azithromycin impurity F
CN108727179B (en) Synthetic method of alpha-allyl substituted alpha, beta-unsaturated ketone, ester or nitrile compound
CN102391170B (en) A kind of preparation method of N, N-diallyl-5-methoxytryptamine hydrochlorides
CN114507240A (en) Preparation method of cyclobutane tetracarboxylic dianhydride
WO2021180874A1 (en) Method for preparing benzamide compound
US20220235010A1 (en) Synthesis method for 1-methyl-1h-indazole-6-carboxylic acid
CN117050011B (en) Method for synthesizing 2-methylquinoline by using vinyl acetate as raw material
CN110563721A (en) Preparation method of azasetron hydrochloride
CN108341770A (en) A kind of preparation method of Sorafenib compound
CN104370807B (en) The synthetic method of a kind of 6-hydroxyl-5-nitronicotinic acid and process for separation and purification thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant