CN106518790A - Synthesis method of 2,4-dichloro quinazoline - Google Patents
Synthesis method of 2,4-dichloro quinazoline Download PDFInfo
- Publication number
- CN106518790A CN106518790A CN201610944870.3A CN201610944870A CN106518790A CN 106518790 A CN106518790 A CN 106518790A CN 201610944870 A CN201610944870 A CN 201610944870A CN 106518790 A CN106518790 A CN 106518790A
- Authority
- CN
- China
- Prior art keywords
- dichloroquinazolines
- synthetic method
- catalyst
- acid
- filtrate
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/002—Mixed oxides other than spinels, e.g. perovskite
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/16—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of arsenic, antimony, bismuth, vanadium, niobium, tantalum, polonium, chromium, molybdenum, tungsten, manganese, technetium or rhenium
- B01J23/24—Chromium, molybdenum or tungsten
- B01J23/30—Tungsten
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2523/00—Constitutive chemical elements of heterogeneous catalysts
Abstract
The invention discloses a synthesis method of 2,4-dichloro quinazoline. The synthesis method comprises the following steps: (1) mixing o-amino benzoyl chloride, carbon tetrachloride, an acid-binding agent, a catalyst, methyl carbamate and an organic solvent; (2) enabling reaction at 100 to 120 DEG C and 0.2 to 0.3 MPa for 5 to 7 hours; (3) heating to 200 to 230 DEG C, and continuously enabling reaction at 0.6 to 0.8 MPa for 20 to 25 hours; (4) filtering out insolubles, and extracting filtrate to obtain white solids. Compared with the prior art, the synthesis method disclosed by the invention has the advantages that the raw materials are readily available, the price is low, and the pollution is low; the reaction steps are relatively short, and one-step reaction is realized; furthermore, no high-toxicity and high-corrosiveness reactants are used, so that the operation is safe; the yield is high and can reach 97.0 percent or above.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to the synthetic method of one kind 2,4- dichloroquinazolines.
Background technology
2,4- dichloroquinazolines are a kind of important medicine and fine-chemical intermediate, with extensive biologically active and medicine
Thing activity, can be used in anticancer, sterilization, desinsection, anti-inflammatory, pain relieving, calmness, step-down, anti-diabetic and the field such as antiviral.With
The downstream product demand of 2,4- dichloroquinazolines increases, and its market prospects is boundless.In prior art, conventional has benzene
Amine/carbobenzoxy isocyanic acid ester process and ortho-aminobenzoic acid/potassium cyanate method, both approaches are required to using limiter trichlorine oxygen
The chlorinating agents such as phosphorus, corrosivity are stronger, additionally, these methods are present, material toxicity is big, be difficult to obtain, and reactions steps are long, and reaction is produced
The shortcomings of rate is relatively low serious with environmental pollution.
The content of the invention
In order to solve the above problems, present invention aim at providing the synthetic method of one kind 2,4- dichloroquinazolines.
Based on this purpose, following technical scheme is this invention takes：The synthetic method of one kind 2,4- dichloroquinazolines, including
Following steps：1）O-amino benzoyl chloride, carbon tetrachloride, acid binding agent, catalyst, methyl carbamate and organic solvent are mixed
Close；2）5～7h is reacted under 100～120 DEG C, 0.2～0.3MPa；3）Be warming up to 200～230 DEG C, under 0.6～0.8MPa after
20～25h of continuous reaction；4）Insoluble matter is filtered, filtrate is extracted and is obtained white solid.
The catalyst is made up of the raw material of following percentage by weight：Chromium oxide 2～3%, the oxidation of tin oxide 5～9%, five two
Vanadium 0.5～2%, tungstic acid 12～15%, remaining be nano titanium oxide.
The preparation method of the catalyst is：By chromium oxide, tin oxide, vanadic anhydride, that tungstic acid is placed in quality is dense
Spend in the nitric acid for 15～20%, stir 2～5h, add nano titanium oxide, stir 30～48h, concentrate and remove moisture, 120 DEG C
After drying 2h, 5h is activated in 300 DEG C and obtained final product.
The mole dosage ratio of the o-amino benzoyl chloride, carbon tetrachloride and methyl carbamate is 1:（1～1.05）:（1
～1.1）；The catalyst amount for the quality of o-amino benzoyl chloride 3～5%.
The acid binding agent is pyridine or 4- picolines, and its consumption is 3～3.12 times of o-amino benzoyl chloride molal quantity.
Step 1）In organic solvent be selected from DMSO, DMF and tetrahydrofuran.
Step 4）It is middle filtrate is extracted include by filtrate to entering in water, extraction, be dried, concentration process, extraction during extraction
Agent is selected from ethyl acetate, ether and chloroform, is dried the drier for adopting and is selected from anhydrous calcium chloride, sodium sulphate and magnesium sulfate.
Compared with prior art, the present invention has following technique effect：
1）Raw material is easy to get, and price is low；
2）Reactions steps are shorter, single step reaction；
3）The reactant for not using high poison and corrosivity strong, safe operation；
4）Yield is high, up to 97.0 more than %, low cost, pollutes little.
Specific embodiment
With reference to specific embodiment, the present invention is further illustrated.
Embodiment 1
The synthetic method of one kind 2,4- dichloroquinazolines, comprises the following steps：
1）O-amino benzoyl chloride, carbon tetrachloride, pyridine, catalyst, methyl carbamate are mixed with DMSO, o-amino benzoyl
The mole dosage ratio of acyl chlorides, carbon tetrachloride and methyl carbamate is 1:1:1, matter of the catalyst amount for o-amino benzoyl chloride
3 % of amount, the consumption of pyridine are 3 times of o-amino benzoyl chloride molal quantity；
2）Mixture is reacted into 5h under 100 DEG C, 0.2MPa；
3）Then mixture is warming up to 200 DEG C again, continues 20～25h of reaction under 0.6MPa and terminate；
4）After cooling, insoluble matter is filtered to remove, then filtrate is poured into water, add ethyl acetate extraction, organic phase is with anhydrous
White solid, i.e. 2,4- dichloroquinazolines, 97.0 % of yield are concentrated to give after calcium chloride dried process.
In the present embodiment, used catalyst is made up of the raw material of following percentage by weight：Chromium oxide 2%, tin oxide 5%, five oxygen
Change two vanadium 0.5%, tungstic acid 12%, remaining be nano titanium oxide.The preparation method of catalyst is：By chromium oxide, tin oxide,
Vanadic anhydride, tungstic acid are placed in the nitric acid that mass concentration is 15%, stir 2h, add nano titanium oxide, stir 30h,
Concentration removes moisture, after 120 DEG C of drying 2h, activates 5h in 300 DEG C.
Embodiment 2
The synthetic method of one kind 2,4- dichloroquinazolines, comprises the following steps：
1）O-amino benzoyl chloride, carbon tetrachloride, pyridine, catalyst, methyl carbamate are mixed with DMF, o-amino benzoyl
The mole dosage ratio of acyl chlorides, carbon tetrachloride and methyl carbamate is 1:1.05:1.1, catalyst amount is anthraniloyl
The 5% of the quality of chlorine, the consumption of pyridine are 3.12 times of o-amino benzoyl chloride molal quantity；
2）Mixture is reacted into 7h under 120 DEG C, 0.3MPa；
3）Then mixture is warming up to 230 DEG C again, 0.8 MPa continues 25 h of reaction and terminates；
4）After cooling, insoluble matter is filtered to remove, then filtrate is poured into water, add chloroform extraction, organic phase anhydrous slufuric acid
White solid i.e. 2,4- dichloroquinazolines, 99.1 % of yield are concentrated to give after sodium dried process.
In the present embodiment, used catalyst is made up of the raw material of following percentage by weight：Chromium oxide 3%, tin oxide 9%, five oxygen
Change two vanadium 2%, 15 % of tungstic acid, remaining be nano titanium oxide.The preparation method of catalyst is：By chromium oxide, tin oxide,
Vanadic anhydride, tungstic acid are placed in the nitric acid that mass concentration is 20%, stir 5h, add nano titanium oxide, stir 48h,
Concentration removes moisture, after 2h drying at 120 DEG C, activates 5h and obtain final product at 300 DEG C.
Embodiment 3
The synthetic method of one kind 2,4- dichloroquinazolines, comprises the following steps：
1）O-amino benzoyl chloride, carbon tetrachloride, 4- picolines, catalyst, methyl carbamate are mixed with tetrahydrofuran,
The mole dosage ratio of o-amino benzoyl chloride, carbon tetrachloride and methyl carbamate is 1:1.02:1.05, catalyst amount is neighbour
4 % of the quality of amino benzoyl chloride, acid binding agent, the consumption of 4- picolines are 3.1 times of o-amino benzoyl chloride molal quantity；
2）Mixture is reacted into 6 h under 110 DEG C, 0.25 MPa；
3）Then mixture is warming up to 210 DEG C again, continues reaction 22h under 0.7MPa and terminate；
4）After cooling, insoluble matter is filtered to remove, then filtrate is poured into water, add ether extraction, organic phase anhydrous slufuric acid
White solid i.e. 2,4- dichloroquinazolines, 98.5 % of yield are concentrated to give after magnesium dried process.
In the present embodiment, used catalyst is made up of the raw material of following percentage by weight：2.6 % of chromium oxide, tin oxide 7.6
%, 1.3 % of vanadic anhydride, 13 % of tungstic acid, remaining be nano titanium oxide.The preparation method of catalyst is：Will oxidation
Chromium, tin oxide, vanadic anhydride, tungstic acid are placed in the nitric acid that mass concentration is 18%, stir 3h, add nanometer titanium dioxide
Titanium, stirs 40h, and concentration removes moisture, after 2h drying at 120 DEG C, activates 5 h and obtain final product at 300 DEG C.
Structural confirmation
The product that embodiment 1-3 is obtained is white solid, while fusing point test, HNMR tests and mass spectrum point are carried out to each product
Analysis, it is really target product that Jing is analyzed to identify products therefrom, and its concrete outcome is：
Fusing point：119～120 DEG C；
Mass spectrum：ESI-MS, 200（M++1）；
Nuclear-magnetism：8.2（D, 1H）,8.0（D, 1H）, 7.9 (t, 1H), 7.7 (M, 1H).
Claims (7)
1. one kind 2, the synthetic method of 4- dichloroquinazolines, it is characterised in that comprise the following steps：1）By anthraniloyl
Chlorine, carbon tetrachloride, acid binding agent, catalyst, methyl carbamate are mixed with organic solvent；2）In 100～120 DEG C, 0.2～
5～7h is reacted under 0.3MPa；3）200～230 DEG C are warming up to, continue 20～25h of reaction under 0.6～0.8MPa；4）Filter not
Molten thing, filtrate is extracted and obtains white solid.
2. the synthetic method of 2,4- dichloroquinazolines as claimed in claim 1, it is characterised in that the catalyst is by following heavy
The raw material of amount percentage is made：Chromium oxide 2～3%, tin oxide 5～9%, vanadic anhydride 0.5～2%, tungstic acid 12～
15%th, remaining is nano titanium oxide.
3. the synthetic method of 2,4- dichloroquinazolines as claimed in claim 2, it is characterised in that the preparation side of the catalyst
Method is：Chromium oxide, tin oxide, vanadic anhydride, tungstic acid are placed in the nitric acid that mass concentration is 15～20%, stirring 2～
5h, adds nano titanium oxide, stirs 30～48h, and concentration removes moisture, after 120 DEG C of drying 2h, activates 5h in 300 DEG C and obtain final product.
4. the synthetic method of 2, the 4- dichloroquinazolines as described in claim 1-3 is arbitrary, it is characterised in that the adjacent aminobenzene
The mole dosage ratio of formyl chloride, carbon tetrachloride and methyl carbamate is 1:（1～1.05）:（1～1.1）, the catalyst use
Measure 3～5% of the quality for o-amino benzoyl chloride.
5. the synthetic method of 2,4- dichloroquinazolines as claimed in claim 4, it is characterised in that the acid binding agent be pyridine or
4- picolines, 3～3.12 times for o-amino benzoyl chloride molal quantity of its consumption.
6. the synthetic method of 2,4- dichloroquinazolines as claimed in claim 4, it is characterised in that step 1）In organic solvent
Selected from DMSO, DMF and tetrahydrofuran.
7. the synthetic method of 2,4- dichloroquinazolines as claimed in claim 4, it is characterised in that step 4）It is middle that filtrate is extracted
Including by filtrate to entering in water, extraction, be dried, concentration process, extractant during extraction is selected from ethyl acetate, ether and chloroform,
Drier when being dried is selected from anhydrous calcium chloride, sodium sulphate and magnesium sulfate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610944870.3A CN106518790B (en) | 2016-11-02 | 2016-11-02 | A kind of synthetic method of 2,4- dichloroquinazoline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610944870.3A CN106518790B (en) | 2016-11-02 | 2016-11-02 | A kind of synthetic method of 2,4- dichloroquinazoline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106518790A true CN106518790A (en) | 2017-03-22 |
| CN106518790B CN106518790B (en) | 2019-01-15 |
Family
ID=58292841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610944870.3A Active CN106518790B (en) | 2016-11-02 | 2016-11-02 | A kind of synthetic method of 2,4- dichloroquinazoline |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106518790B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002076976A2 (en) * | 2001-03-23 | 2002-10-03 | Bayer Corporation | Rho-kinase inhibitors |
| WO2012044090A2 (en) * | 2010-09-29 | 2012-04-05 | 크리스탈지노믹스(주) | Novel aminoquinazoline compound having a protein-kinase inhibiting action |
| WO2016003225A2 (en) * | 2014-07-03 | 2016-01-07 | 덕산네오룩스 주식회사 | Compound for organic electronic element, organic electronic element using same, and electronic device comprising same |
-
2016
- 2016-11-02 CN CN201610944870.3A patent/CN106518790B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002076976A2 (en) * | 2001-03-23 | 2002-10-03 | Bayer Corporation | Rho-kinase inhibitors |
| WO2012044090A2 (en) * | 2010-09-29 | 2012-04-05 | 크리스탈지노믹스(주) | Novel aminoquinazoline compound having a protein-kinase inhibiting action |
| WO2016003225A2 (en) * | 2014-07-03 | 2016-01-07 | 덕산네오룩스 주식회사 | Compound for organic electronic element, organic electronic element using same, and electronic device comprising same |
Non-Patent Citations (3)
| Title |
|---|
| KAMALDEEP P. ET AL.: "Synthesis and in vitro antitumor evaluation of primary amine substituted quinazoline linked benzimidazole", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| SHAH D.R.ET AL.: "Synthesis and In Vitro Antimicrobial Evaluation of Piperazine Substituted Quinazoline Based Thiourea/Thiazolidinone/Chalcone Hybrids", 《RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY》 * |
| ZHAO S.Z.ET AL.: "Hybrid diarylbenzopyrimidine non-nucleoside reverse transcriptase inhibitors as promising new leads for improved anti-HIV-1 chemotherapy", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106518790B (en) | 2019-01-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106117128A (en) | A kind of micro passage reaction prepares the method for pyridone chlorine addition product continuously | |
| US20100065416A1 (en) | 6-chloro-2-trichloromethyl pyridine preparation method | |
| CN106800512A (en) | The preparation method and preparation facilities of a kind of 3,5 dinitro o methyl benzoic acid | |
| CN112679421A (en) | Synthesis method of (R) -3-chloropyridyl-2-trifluoroethylamine hydrochloride | |
| CN105566215A (en) | Preparation method of Stivarga | |
| CN104829495A (en) | Method for preparation of high purity and high yield metformin hydrochloride by two-component solvent | |
| CN106117148A (en) | A kind of preparation and purification technique of Lopinavir | |
| CN106632244A (en) | A novel synthetic method for preparing an anticancer medicine Niraparib | |
| CN106397358B (en) | A kind of method of the micro passage reaction synthesis fluoro- 4- of 3- (4- morpholinyl) aniline | |
| CN102304116A (en) | Fluorescein compound and preparation method thereof | |
| SU489312A3 (en) | The method of producing tetrachlorophthalonitrile | |
| CN106518790A (en) | Synthesis method of 2,4-dichloro quinazoline | |
| CN106496184A (en) | A kind of preparation method of 2 thiophenic acid | |
| CN113980024A (en) | Preparation method of Ruideciclovir intermediate compound | |
| CN106378131A (en) | A catalyst for carbonate synthesis from urea alcoholysis and a preparing method thereof | |
| DE2256170C3 (en) | Continuous process for the production of copper phthalocyanine | |
| CN104557613A (en) | Deslagging method for continuous production of methyl isocyanate | |
| CN108129402A (en) | Using (diphenyl) acetylene compounds as the method for Material synthesis 2- phenylquinazoline ketone compounds | |
| EP0153593B1 (en) | Process for the preparation of cyanuric acid | |
| CN217140330U (en) | Device for continuously producing hydantoin by fixed bed reactor | |
| CN115583894B (en) | Method and device for continuously producing 2-nitro-4-methoxy acetanilide | |
| CN106749237A (en) | The preparation method of Zolpidemtar Trate and its intermediate | |
| CN103224452B (en) | 2-bromine-4,6-dichloroaniline preparation method | |
| JPS60501056A (en) | Preparation of polychlorinated pyridine mixtures by liquid phase chlorination of 3,5-lutidine or 3,5-lutidine hydrochloride | |
| CN103772282B (en) | A kind of preparation method of the 3-tertiary butyl-1H-pyrazoles-4-formaldehyde |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wang Yong Inventor after: Luo Beibei Inventor after: Du Rui Inventor after: Zhang Yaxun Inventor after: Ren Zhao Inventor after: Zhang Lipan Inventor after: Wang Fayun Inventor after: Liu Hongwei Inventor after: Zhang Jianjun Inventor after: Zhao Mengyao Inventor after: Zhang Wenjie Inventor after: Zhou Li Inventor after: Guan Bingfeng Inventor before: Wang Yong Inventor before: Zhang Lipan Inventor before: Wang Fayun Inventor before: Guo Qingzhao Inventor before: Luo Beibei Inventor before: Du Rui Inventor before: Hong Huijie Inventor before: Ren Zhao Inventor before: Zhang Yaxun |
|
| CB03 | Change of inventor or designer information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221116 Address after: 251907 Donggang 5th Road, Beihai Economic Development Zone, Binzhou City, Shandong Province Patentee after: BINZHOU YUNENG CHEMICAL Co.,Ltd. Address before: 450002 No. 87, Wenhua Road, Jinshui District, Henan, Zhengzhou Patentee before: HENAN BUSINESS RESEARCH INSTITUTE Co.,Ltd. |
|
| TR01 | Transfer of patent right |