CN106518790B - A kind of synthetic method of 2,4- dichloroquinazoline - Google Patents
A kind of synthetic method of 2,4- dichloroquinazoline Download PDFInfo
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- CN106518790B CN106518790B CN201610944870.3A CN201610944870A CN106518790B CN 106518790 B CN106518790 B CN 106518790B CN 201610944870 A CN201610944870 A CN 201610944870A CN 106518790 B CN106518790 B CN 106518790B
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- dichloroquinazoline
- synthetic method
- chloride
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- anthranilic
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- TUQSVSYUEBNNKQ-UHFFFAOYSA-N 2,4-dichloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC(Cl)=C21 TUQSVSYUEBNNKQ-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000010189 synthetic method Methods 0.000 title claims description 13
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims abstract description 22
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003054 catalyst Substances 0.000 claims abstract description 20
- RLCMQWBYWOIEGD-UHFFFAOYSA-N 2-aminobenzoyl chloride Chemical compound NC1=CC=CC=C1C(Cl)=O RLCMQWBYWOIEGD-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000000706 filtrate Substances 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 239000007787 solid Substances 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 239000011230 binding agent Substances 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical compound O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 claims description 12
- XOLBLPGZBRYERU-UHFFFAOYSA-N tin dioxide Chemical compound O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 claims description 11
- 229910001887 tin oxide Inorganic materials 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 9
- 229910000423 chromium oxide Inorganic materials 0.000 claims description 9
- SOQBVABWOPYFQZ-UHFFFAOYSA-N oxygen(2-);titanium(4+) Chemical compound [O-2].[O-2].[Ti+4] SOQBVABWOPYFQZ-UHFFFAOYSA-N 0.000 claims description 9
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 5
- 229910017604 nitric acid Inorganic materials 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 229910052720 vanadium Inorganic materials 0.000 claims description 4
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 claims description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 3
- 235000011152 sodium sulphate Nutrition 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 claims description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000002274 desiccant Substances 0.000 claims description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 2
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 2
- ZNOKGRXACCSDPY-UHFFFAOYSA-N tungsten trioxide Chemical compound O=[W](=O)=O ZNOKGRXACCSDPY-UHFFFAOYSA-N 0.000 claims 4
- 239000012141 concentrate Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- 239000000376 reactant Substances 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- CMPGARWFYBADJI-UHFFFAOYSA-L tungstic acid Chemical compound O[W](O)(=O)=O CMPGARWFYBADJI-UHFFFAOYSA-L 0.000 description 8
- 239000000203 mixture Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 238000010792 warming Methods 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-N anhydrous cyanic acid Natural products OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- -1 carbobenzoxy isocyanic acid ester Chemical class 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
一种2,4‑二氯喹唑啉的合成方法，包括以下步骤：1）将邻氨基苯甲酰氯、四氯化碳、缚酸剂、催化剂、氨基甲酸甲酯与有机溶剂混合；2）于100～120℃、0.2～0.3MPa下反应5～7h；3）升温至200～230℃，于0.6～0.8MPa下继续反应20～25h；4）滤除不溶物，将滤液提取得到白色固体。与现有技术相比，本发明原料易得，价格低，污染小；反应步骤较短，一步反应；且不使用高毒和腐蚀性强的反应物，操作安全；产率高，达97.0%以上。A method for synthesizing 2,4-dichloroquinazoline, comprising the following steps: 1) mixing anthranilic acid chloride, carbon tetrachloride, an acid binding agent, a catalyst, methyl carbamate and an organic solvent; 2) mixing in an organic solvent; React at 100-120°C and 0.2-0.3MPa for 5-7h; 3) Raise the temperature to 200-230°C and continue the reaction at 0.6-0.8MPa for 20-25h; 4) Filter off insolubles and extract the filtrate to obtain a white solid. Compared with the prior art, the present invention has the advantages of easy availability of raw materials, low price and little pollution; short reaction steps, one-step reaction; no highly toxic and corrosive reactants, safe operation; high yield, up to 97.0% 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- dichloroquinazoline.
Background technique
2,4- dichloroquinazolines are a kind of important medicine and fine-chemical intermediate, have extensive bioactivity and medicine
Object activity can be used in anticancer, sterilization, desinsection, anti-inflammatory, analgesic, calm, decompression, anti-diabetic and the fields such as antiviral.With
The downstream product demand of 2,4- dichloroquinazolines increases, and market prospects are boundless.In the prior art, there are commonly benzene
Amine/carbobenzoxy isocyanic acid ester process and ortho-aminobenzoic acid/potassium cyanate method, both methods are required to using limiter trichlorine oxygen
The chlorinating agents such as phosphorus, corrosivity is stronger, in addition, that there are material toxicities is big, is difficult to obtain for these methods, reaction step is long, and reaction produces
The disadvantages of rate is lower and environmental pollution is serious.
Summary of the invention
To solve the above-mentioned problems, it is an object of that present invention to provide the synthetic methods of one kind 2,4- dichloroquinazoline.
Based on this purpose, this invention takes following technical solutions: the synthetic method of one kind 2,4- dichloroquinazoline, including
Following steps: 1) o-amino benzoyl chloride, carbon tetrachloride, acid binding agent, catalyst, methyl carbamate and organic solvent are mixed
It closes；2) 5~7h is reacted under 100~120 DEG C, 0.2~0.3MPa；3) 200~230 DEG C are warming up to, under 0.6~0.8MPa after
20~25h of continuous reaction；4) insoluble matter is filtered out, filtrate is extracted to obtain white solid.
The catalyst is made of the raw material of following weight percent: 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 dioxide.
The catalyst the preparation method comprises the following steps: by chromium oxide, tin oxide, vanadic anhydride, that tungstic acid is placed in quality is dense
In the nitric acid that degree is 15~20%, 2~5h of stirring, addition nano-titanium dioxide, 30~48h of stirring, concentration removing moisture, 120 DEG C
After drying 2h, in 300 DEG C of activation 5h to obtain the 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 is the 3~5% of the quality of o-amino benzoyl chloride.
The acid binding agent is pyridine or 4- picoline, and dosage is 3~3.12 times of o-amino benzoyl chloride molal quantity.
Organic solvent in step 1) is selected from DMSO, DMF and tetrahydrofuran.
Filtrate extracted in step 4) include by filtrate to enter in water, extraction, dry, concentration process, extraction when extraction
Agent is selected from ethyl acetate, ether and chloroform, and the dry desiccant used is selected from anhydrous calcium chloride, sodium sulphate and magnesium sulfate.
Compared with prior art, the present invention has following technical effect that
1) raw material is easy to get, and price is low；
2) reaction step is shorter, single step reaction；
3) reactant strong without using high poison and corrosivity, safe operation；
4) yield is high, at low cost up to 97.0 % or more, pollutes small.
Specific embodiment
Combined with specific embodiments below, the present invention is further illustrated.
Embodiment 1
The synthetic method of one kind 2,4- dichloroquinazoline, comprising the following steps:
1) o-amino benzoyl chloride, carbon tetrachloride, pyridine, catalyst, methyl carbamate and DMSO are mixed, adjacent amino
The mole dosage ratio of chlorobenzoyl chloride, carbon tetrachloride and methyl carbamate is 1:1:1, and catalyst amount is o-amino benzoyl chloride
Quality 3 %, the dosage of pyridine is 3 times of o-amino benzoyl chloride molal quantity；
2) mixture is reacted into 5h under 100 DEG C, 0.2MPa；
3) mixture is then warming up to 200 DEG C again, the reaction was continued under 0.6MPa, and 20~25h terminates；
4) after cooling, it is filtered to remove insoluble matter, is then poured into water filtrate, ethyl acetate extraction is added, organic phase is used
Anhydrous calcium chloride is concentrated to get white solid, i.e. 2,4- dichloroquinazoline, 97.0 % of yield after being dried.
Used catalyst is made of the raw material of following weight percent in the present embodiment: chromium oxide 2%, tin oxide 5%, five oxygen
Change two vanadium 0.5%, tungstic acid 12%, remaining be nano-titanium dioxide.Catalyst the preparation method comprises the following steps: by chromium oxide, tin oxide,
Vanadic anhydride, tungstic acid are placed in the nitric acid that mass concentration is 15%, stir 2h, and nano-titanium dioxide is added, and stir 30h,
It is concentrated and removes moisture, after 120 DEG C of drying 2h, in 300 DEG C of activation 5h.
Embodiment 2
The synthetic method of one kind 2,4- dichloroquinazoline, comprising the following steps:
1) o-amino benzoyl chloride, carbon tetrachloride, pyridine, catalyst, methyl carbamate and DMF are mixed, adjacent amino
The mole dosage ratio of chlorobenzoyl chloride, carbon tetrachloride and methyl carbamate is 1:1.05:1.1, and catalyst amount is adjacent aminobenzene
The 5% of the quality of formyl chloride, the dosage 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) mixture is then warming up to 230 DEG C again, 0.8 MPa, the reaction was continued, and 25 h terminate；
4) after cooling, it is filtered to remove insoluble matter, is then poured into water filtrate, be added chloroform extraction, organic phase is with anhydrous
Sodium sulphate is concentrated to get white solid i.e. 2,4- dichloroquinazoline, 99.1 % of yield after being dried.
Used catalyst is made of the raw material of following weight percent in the present embodiment: chromium oxide 3%, tin oxide 9%, five oxygen
Change two vanadium 2%, 15 % of tungstic acid, remaining be nano-titanium dioxide.Catalyst the preparation method comprises the following steps: by chromium oxide, tin oxide,
Vanadic anhydride, tungstic acid are placed in the nitric acid that mass concentration is 20%, stir 5h, and nano-titanium dioxide is added, and stir 48h,
Concentration removes moisture, at 120 DEG C after 2h drying, activates 5h at 300 DEG C to obtain the final product.
Embodiment 3
The synthetic method of one kind 2,4- dichloroquinazoline, comprising the following steps:
1) by o-amino benzoyl chloride, carbon tetrachloride, 4- picoline, catalyst, methyl carbamate and tetrahydrofuran
Mixing, the mole dosage ratio of o-amino benzoyl chloride, carbon tetrachloride and methyl carbamate are 1:1.02:1.05, and catalyst is used
Amount is 4 % of the quality of o-amino benzoyl chloride, and acid binding agent, the dosage of 4- picoline is o-amino benzoyl chloride molal quantity
3.1 again；
2) mixture is reacted into 6 h under 110 DEG C, 0.25 MPa；
3) mixture is then warming up to 210 DEG C again, the reaction was continued at 0.7MPa, and 22h terminates；
4) after cooling, it is filtered to remove insoluble matter, is then poured into water filtrate, be added ether extraction, organic phase is with anhydrous
Magnesium sulfate is concentrated to get white solid i.e. 2,4- dichloroquinazoline, 98.5 % of yield after being dried.
Used catalyst is made of the raw material of following weight percent in the present embodiment: 2.6 % of chromium oxide, tin oxide 7.6
%, 1.3 % of vanadic anhydride, 13 % of tungstic acid, remaining be nano-titanium dioxide.Catalyst the preparation method comprises the following steps: will oxidation
Chromium, tin oxide, vanadic anhydride, tungstic acid are placed in the nitric acid that mass concentration is 18%, stir 3h, and nanometer titanium dioxide is added
Titanium stirs 40h, and concentration removes moisture, at 120 DEG C after 2h drying, 5 h is activated at 300 DEG C to obtain the final product.
Structural confirmation
The product that embodiment 1-3 is obtained is white solid, while carrying out fusing point test, HNMR test and mass spectrum to each product
Analysis, being analyzed to identify products therefrom is really target product, concrete outcome are as follows:
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 (5)
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-
2016
- 2016-11-02 CN CN201610944870.3A patent/CN106518790B/en active Active
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| 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 |
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| Hybrid diarylbenzopyrimidine non-nucleoside reverse transcriptase inhibitors as promising new leads for improved anti-HIV-1 chemotherapy;Zhao S.Z.et al.;《Bioorganic & Medicinal Chemistry》;20100604;第18卷;第5039-5047页 |
| Synthesis and In Vitro Antimicrobial Evaluation of Piperazine Substituted Quinazoline Based Thiourea/Thiazolidinone/Chalcone Hybrids;Shah D.R.et al.;《Russian Journal of Bioorganic Chemistry》;20141231;第41卷(第2期);第209-222页 |
| Synthesis and in vitro antitumor evaluation of primary amine substituted quinazoline linked benzimidazole;Kamaldeep P. et al.;《Bioorganic & Medicinal Chemistry Letters》;20131208;第24卷;第624-629页 |
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