CN105418499A - Preparation method of acridine compound - Google Patents
Preparation method of acridine compound Download PDFInfo
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- CN105418499A CN105418499A CN201510813903.6A CN201510813903A CN105418499A CN 105418499 A CN105418499 A CN 105418499A CN 201510813903 A CN201510813903 A CN 201510813903A CN 105418499 A CN105418499 A CN 105418499A
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- compound
- acridine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/02—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with only hydrogen, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention relates to a preparation method of an acridine compound. The structural formula of the prepared acridine compound is shown in the specification, wherein R1, R2 and R3 are selected from hydrogen atoms, alkyl, aryl, halogens, alkoxy, aryloxy, trifluoromethyl and the like. A dehydrogenation method comprises the steps that o-amino benzophenone and cyclohexanone serve as the reaction raw materials, methylbenzene serves as solvent, a reaction is conducted for 8 h at 150 DEG C under acid catalysis, and after the reaction is completed, a quinoline compound is obtained through concentration and column chromatography separation; the quinoline compound is reacted for 6 h on the condition that palladium trifluoroacetate and 1,10-phenanthroline hydrate serve as catalysts, NMP serves as solvent, O2 atmosphere exists, and the temperature is 100 DEG C, extraction, concentration and column chromatography purification are conducted, and the acridine compound is obtained. The yield ranges from 60 percent to 80 percent. According to the preparation method of the acridine compound, the o-amino benzophenone and the cyclohexanone serve as substrates, the quinoline compound is obtained through a Friedlander synthesis method, and an acridine derivative is obtained through a palladium catalysis and hydrogen transfer method, so that the preparation method of the acridine compound has the advantages that the raw materials are stable and easy to obtain, the product selectivity is good, operation is easy, and the preparation method is suitable for industrial production.
Description
Technical field
The present invention is with a kind of preparation method of acridine compound.
Background technology
Natural acridine and the anthracene of structural similitude coexist in coal tar.Germanization scholar carga thunder shellfishes in 1870 and Heinrich Caro first time in the anthracene component coal tar has isolated acridine (Chem.Soc.Rev., 2001,30,70).Acridine derivatives has very unique biological activity, is widely used in medical aspect, has antitumor, antibacterial, anti-inflammatory, the drug effect such as treatment acquired immune deficiency syndrome (AIDS) and senile dementia.Acridine compound is reaction intermediate important in organic synthesis, and the synthesis about acridine compound has many bibliographical informations.Bernthsen reaction (J.Mol.Spectrosc., 2011,268,66) is the earliest for the synthesis of the method for acridine derivatives.Zimmerman etc. report organometallic reagent and naphthazin(e) ketone derivatives reacts the method (Proc.Natl.Acad.Sci.USA generating acridine compound; 2007; 104; 17347.); first the method protects the reactive hydrogen on the nitrogen-atoms of azepine anthrone, avoids reacting with organometallic reagent, then reacts with organometallic reagent (such as grignard reagent); finally use HCl treatment, obtain acridine derivatives.The present invention for substrate, obtains quinoline compound by Friedl nder synthesis method with adjacent aminobenzophenone and pimelinketone, generates Acridine derivatives again by palladium chtalyst hydrogen transference method.Compared with existing acridine compou nd synthesis method, the present invention has the features such as cheaper starting materials is easy to get, good product selectivity, simple to operate, applicable suitability for industrialized production.
Summary of the invention
A kind of preparation method of acridine compound.The present invention for substrate, has that cheaper starting materials is easy to get with adjacent aminobenzophenone and pimelinketone, good product selectivity, simple to operate, be applicable to the features such as suitability for industrialized production.
For achieving the above object, the acridine compounds that this experiment provides as Fig. 1, wherein R
1, R
2, R
3for hydrogen atom, alkyl, aryl, halogen, alkoxyl group, aryloxy, trifluoromethyl etc.The method that this experiment provides, key step is: adjacent aminobenzophenone and pimelinketone are reaction raw materials, and solvent made by toluene, and under the catalysis of acid, 150 ° of C react 8 hours, and after reaction terminates, concentrated, column chromatography for separation obtains quinoline compound.Quinoline compound is at palladium trifluoroacetate, and under the catalysis of 1,10-phenanthroline, NMP makees solvent, O
2atmosphere, under 100 ° of C temperature condition after 6 hours, extraction, concentrated, column chromatography is purified, and obtains acridine compounds.Productive rate is 60% ~ 80%.
Gained compound through nmr spectrum (
1h-NMR and
13c-NMR) and high resolution mass spectrum determine, structure is errorless.
The present invention adopts substituted or unsubstituted adjacent aminobenzophenone and pimelinketone can directly commercially.
The catalyzer palladium trifluoroacetate (5mol%) that the present invention adopts, 1,10-phenanthroline (10mol%).
Column chromatography of the present invention eluent used is sherwood oil and ethyl acetate.
Accompanying drawing explanation
Fig. 1 is acridine compounds structure iron;
Fig. 2 is embodiment procedure chart.
Embodiment
Its reaction process is as Fig. 2.
Concrete preparation method's citing: adjacent aminobenzophenone and pimelinketone (1:1.2, amount of substance ratio) are put into reaction tubes, the citric acid of 10% equivalent, and then add 2 milliliters of toluene, 150 ° of C react 8 hours; After reaction terminates, reaction solution concentrates, and column chromatography is purified, and eluent is sherwood oil and ethyl acetate, obtains quinoline compound, and yield is 92%.Quinoline compound, at palladium trifluoroacetate (5mol%), under 1,10-phenanthroline (10mol%) catalysis, adds 2 milliliters of NMP, O
2atmosphere, reacts 6 hours under 100 ° of C temperature condition.After reaction terminates, extraction, concentrated, column chromatography is purified, and eluent is sherwood oil and ethyl acetate, obtains acridine compounds, and yield is 75%.Proton nmr spectra
1hNMR (400MHz, CDCl
3) δ 8.27 (dd, 2H,
j=15.2,9.0Hz) 7.89 (dd, 1H,
j=9.2,1.8Hz) 7.72 (dd, 2H,
j=17.7,8.5Hz), 7.63 – 7.23 (m, 10H), 1.31 (s, 9H); Carbon-13 nmr spectra
13cNMR (75MHz, CDCl
3) δ 148.7,147.1,135.8,130.3,129.8,129.5,128.3,128.2,126.7,125.5,125.0.
The present invention relates to a kind of preparation method of acridine compound, with adjacent aminobenzophenone and pimelinketone for substrate, obtain quinoline compound by Friedl nder synthesis method, generate Acridine derivatives by palladium chtalyst hydrogen transference method.Compared with existing acridine compou nd synthesis method, the present invention has the features such as cheaper starting materials is easy to get, good product selectivity, simple to operate, applicable suitability for industrialized production.Above-mentioned concrete implementation example is tightly preferred embodiments of the present invention, is not restriction the present invention being made to other form.
Claims (2)
1. prepare the method for compound claims, key step is:
A) adjacent aminobenzophenone and pimelinketone (1:1.2, amount of substance ratio) are put into reaction tubes, the acid (as citric acid) of 10% equivalent, then add a little toluene, 150 ° of C react 8 hours;
B) after reaction terminates, reaction solution concentrates, and column chromatography is purified, and eluent is sherwood oil and ethyl acetate, obtains quinoline compound;
C) quinoline compound is at palladium trifluoroacetate (5mol%), under 1,10-phenanthroline (10mol%) catalysis, adds a little NMP, O
2atmosphere, reacts 6 hours under 100 ° of C temperature condition, and after reaction terminates, extraction, concentrated, column chromatography is purified, and eluent is sherwood oil and ethyl acetate, obtains acridine compounds.
2. the catalyzer that the present invention adopts is palladium trifluoroacetate (5mol%), and 1,10-phenanthroline (10mol%), solvent is NMP.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510813903.6A CN105418499A (en) | 2015-11-23 | 2015-11-23 | Preparation method of acridine compound |
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| CN201510813903.6A CN105418499A (en) | 2015-11-23 | 2015-11-23 | Preparation method of acridine compound |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109956902A (en) * | 2017-12-14 | 2019-07-02 | 中国科学院大连化学物理研究所 | A method of preparing azepine anthracene compound |
| CN109970643A (en) * | 2019-04-19 | 2019-07-05 | 哈尔滨工业大学（威海） | A kind of green synthesis method of the Activities of Tetrahydroacridine Derivatives under the promotion of iodine anion |
-
2015
- 2015-11-23 CN CN201510813903.6A patent/CN105418499A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109956902A (en) * | 2017-12-14 | 2019-07-02 | 中国科学院大连化学物理研究所 | A method of preparing azepine anthracene compound |
| CN109970643A (en) * | 2019-04-19 | 2019-07-05 | 哈尔滨工业大学（威海） | A kind of green synthesis method of the Activities of Tetrahydroacridine Derivatives under the promotion of iodine anion |
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Application publication date: 20160323 |
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