WO2022166441A1 - Preparation method for 2-acetyl-1,10-phenanthroline - Google Patents

Preparation method for 2-acetyl-1,10-phenanthroline Download PDF

Info

Publication number
WO2022166441A1
WO2022166441A1 PCT/CN2021/139664 CN2021139664W WO2022166441A1 WO 2022166441 A1 WO2022166441 A1 WO 2022166441A1 CN 2021139664 W CN2021139664 W CN 2021139664W WO 2022166441 A1 WO2022166441 A1 WO 2022166441A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
preparation
acetyl
present
phenanthroline
Prior art date
Application number
PCT/CN2021/139664
Other languages
French (fr)
Chinese (zh)
Inventor
韩得满
李运广
武承林
李培贤
Original Assignee
台州市生物医化产业研究院有限公司
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 台州市生物医化产业研究院有限公司 filed Critical 台州市生物医化产业研究院有限公司
Priority to GB2304953.9A priority Critical patent/GB2614199A/en
Publication of WO2022166441A1 publication Critical patent/WO2022166441A1/en

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the invention relates to the technical field of organic synthesis, in particular to a preparation method of 2-acetyl-1,10-phenanthroline.
  • 2-acetyl-1,10-phenanthroline is mainly used in optoelectronic materials, which mainly uses 2-bromophenanthroline to extract bromine through butyllithium at -78 °C, and then react with N,N- Prepared by dimethylacetamide reaction.
  • the raw materials of the above preparation method are expensive, the synthesis conditions are too harsh, and the industrialization advantage is not large.
  • the object of the present invention is to provide a preparation method of 2-acetyl-1,10-phenanthroline.
  • the preparation method has simple synthetic route, easy industrial production, and green and friendly raw materials.
  • the invention provides a kind of preparation method of 2-acetyl-1,10-phenanthroline, comprising the following steps:
  • the 2-acetyl-1,2-dihydrophenanthroline, the oxidizing agent and the second organic solvent are mixed to undergo an oxidation reaction to obtain the 2-acetyl-1,10-phenanthroline.
  • the molar ratio of the 8-aminoquinoline to 3-acetylacrolein is 1:(0.9-3.0).
  • the acid includes an organic acid or an inorganic acid
  • the mass ratio of the acid to the 8-aminoquinoline is 100:(60-145).
  • the organic acid includes one or more of acetic acid, polyphosphoric acid, phosphorus oxychloride, trifluoroacetic acid and trifluoromethanesulfonic acid;
  • the inorganic acid includes one or more of hydrochloric acid, sulfuric acid and vanadic acid.
  • the temperature of the addition reaction is 50-65° C., and the time is 15-25 h.
  • the catalyst is one or more of polyphosphoric acid, vanadic acid, concentrated hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid and trifluoroacetic acid;
  • the mass concentration of the concentrated hydrochloric acid is 30-36%.
  • the mass ratio of the 4-oxo-3-(quinoline-8-amino)pentanal to the catalyst is 1:(0.1-10).
  • the temperature of the cyclization reaction is 77-82° C., and the time is 15-25 h.
  • the oxidant is tetrachlorobenzoquinone, dichlorodicyanobenzoquinone, potassium permanganate, hydrogen peroxide, tert-butanol peroxy or peracetic acid.
  • the mass ratio of the 2-acetyl-1,2-dihydrophenanthroline to the oxidizing agent is (70-120): (35-200).
  • the temperature of the oxidation reaction is room temperature, and the time is 5-10 h.
  • the steps of solid precipitation, first filtration, pulping, second filtration, rinsing and drying are performed in sequence.
  • the precipitation of solid is to add water or saturated aqueous sodium bicarbonate solution to the product system obtained after the oxidation reaction is completed to precipitate the solid;
  • the volume ratio of the water or saturated aqueous sodium bicarbonate solution to the second organic solvent is 30:13 or 30:15.
  • the beating is mixing the filter cake obtained by the first filtration with toluene and beating at a temperature of 70° C. for 30 minutes.
  • the invention provides a preparation method of 2-acetyl-1,10-phenanthroline, comprising the following steps: in a protective atmosphere, mixing 8-aminoquinoline, 3-acetyl acrolein, an acid and a solvent, Addition reaction is carried out to obtain 4-oxo-3-(quinoline-8-amino)pentanal; the 4-oxo-3-(quinoline-8-amino)pentanal, the catalyst and the first organic
  • the solvent is mixed, and a cyclization reaction is carried out to obtain 2-acetyl-1,2-dihydrophenanthroline; the 2-acetyl-1,2-dihydrophenanthroline, the oxidant and the second organic solvent are mixed, An oxidation reaction occurs to give the 2-acetyl-1,10-phenanthroline.
  • the preparation method has simple synthetic route, mild reaction conditions, easy industrial production, and green and friendly preparation raw materials.
  • Fig. 1 is the nuclear magnetic spectrum of 2-acetyl-1,10-phenanthroline prepared in Example 1.
  • the invention provides a kind of preparation method of 2-acetyl-1,10-phenanthroline, comprising the following steps:
  • the 2-acetyl-1,2-dihydrophenanthroline, the oxidizing agent and the second organic solvent are mixed to undergo an oxidation reaction to obtain the 2-acetyl-1,10-phenanthroline.
  • the preparation process of the 2-acetyl-1,10-phenanthroline is preferably as shown in formula I:
  • the present invention 8-aminoquinoline, 3-acetylacrolein, acid and solvent are mixed in a protective atmosphere, and an addition reaction is carried out to obtain 4-oxo-3-(quinoline-8-amino)pentanal.
  • the present invention does not have any special limitation on the protective atmosphere, and a non-oxygen atmosphere well-known to those skilled in the art can be used.
  • the protective atmosphere is specifically a nitrogen atmosphere.
  • the structural formula of the 8-aminoquinoline is The 8-aminoquinoline is preferably a commercially available product; the structural formula of the 3-acetyl acrolein is The structural formula of described 4-oxo-3-(quinoline-8-amino) pentanal is
  • the acid preferably includes an organic acid or an inorganic acid; the inorganic acid preferably includes one or more of hydrochloric acid, sulfuric acid and vanadic acid; in the present invention, when the inorganic acid includes hydrochloric acid, The hydrochloric acid is preferably mixed in the form of a solution, and the mass concentration of the hydrochloric acid is preferably 30-36%; when the inorganic acid includes sulfuric acid and/or vanadic acid, both the sulfuric acid and vanadic acid are preferably sulfuric acid or vanadium. Pure acid.
  • the organic acid preferably includes one or more of acetic acid, polyphosphoric acid, phosphorus oxychloride, trifluoroacetic acid and trifluoromethanesulfonic acid. The acid acts as a catalyst to promote the addition reaction.
  • the solvent includes water and alcohol-based organic solvent; the alcohol-based organic solvent is more preferably methanol.
  • the present invention does not have any special limitation on the ratio of the water and the alcoholic organic solvent, and can be mixed according to any ratio.
  • the alcoholic organic solvent is methanol, and the volume ratio of the water to the alcoholic organic solvent is 3:4 and 1:2.
  • the use of a mixed solvent including water and an alcoholic organic solvent can prevent the polymerization of 3-acetyl acrolein and the uniformity of the system, and further improve the product yield.
  • the molar ratio of the 8-aminoquinoline and 3-acetylacrolein is preferably 1:(0.9-3.0), more preferably 1:(1.5-2.5); the acid and the 8
  • the mass ratio of -aminoquinoline is preferably 100:(60-145), more preferably 100:(70-75).
  • the mass ratio of the 8-aminoquinoline to the solvent is preferably 1 g: (3-20) mL, more preferably 1 g: (4-7) mL.
  • the present invention does not have any special limitation on the mixing, and it can be carried out by a process well known to those skilled in the art.
  • the temperature of the addition reaction is preferably 50-65°C, more preferably 55-60°C; the time is preferably 15-25h, more preferably 18-23h.
  • the present invention also preferably includes filtration; the present invention does not have any special limitation on the filtration, and can be performed by a process well known to those skilled in the art.
  • the present invention mixes the 4-oxo-3-(quinoline-8-amino)pentanal, the catalyst and the first organic solvent , cyclization reaction was carried out to obtain 2-acetyl-1,2-dihydrophenanthroline.
  • the catalyst is preferably one or more of polyphosphoric acid, vanadic acid, concentrated hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid and trifluoroacetic acid, and the mass concentration of the concentrated hydrochloric acid is preferably 30 ⁇ 36%; when the catalysts are two or more of the above specific options, the present invention does not have any special restrictions on the proportion of the above specific substances, and the mixture can be carried out according to any proportion.
  • the catalyst is polyphosphoric acid and vanadic acid; the mass ratio of the polyphosphoric acid and vanadic acid is specifically 45:1.
  • the first organic solvent is preferably one or more of ethyl acetate, methyl tert-butyl ether, toluene, chlorinated alkanes and polyphosphoric acid; when the first organic solvent is the above
  • the present invention does not have any special limitation on the mixing ratio of the above-mentioned specific substances, and the mixture can be carried out according to any mixing ratio.
  • the first organic solvent is ethyl acetate.
  • the mass ratio of the 4-oxo-3-(quinoline-8-amino)pentanal to the catalyst is preferably 1:(0.1-10), more preferably 1:(0.3-1).
  • the mass ratio of the 4-oxo-3-(quinoline-8-amino)pentanal to the volume of the first organic solvent is preferably 1 g: (3-20) mL, more preferably 1 g: (3 to 5) mL.
  • the present invention does not have any special limitation on the mixing, and it can be carried out by a process well known to those skilled in the art.
  • the temperature of the cyclization reaction is preferably 77-82°C, more preferably 80°C; the time is preferably 15-25h, more preferably 18-22h.
  • the cyclization reaction is preferably carried out under reflux conditions.
  • the present invention also preferably includes the process of successively recovering the solvent and using acetic acid jacket to steam; the method of recovering the solvent is preferably reduced pressure distillation; the process of using the acetic acid jacket to steam is preferably reduced pressure. Distilled.
  • the catalyst includes polyphosphoric acid or the first organic solvent includes polyphosphoric acid
  • the definition of can use the type well-known to those skilled in the art.
  • the present invention mixes the 2-acetyl-1,2-dihydrophenanthroline, an oxidizing agent and a second organic solvent, and an oxidation reaction occurs to obtain The 2-acetyl-1,10-phenanthroline.
  • the oxidant is preferably tetrachlorobenzoquinone, dichlorodicyanobenzoquinone, potassium permanganate, hydrogen peroxide, tert-butanol peroxy or peracetic acid, more preferably tetrachlorobenzoquinone or peroxygen Acetic acid; when the catalyst is peracetic acid, the peracetic acid is preferably added in the form of a solution; the mass concentration of the peracetic acid is preferably 35%.
  • the second organic solvent is preferably acetic acid, dichloromethane, chloroform, dichloroethane, toluene or an ether solvent, more preferably acetic acid.
  • the mass ratio of the 2-acetyl-1,2-dihydrophenanthroline to the oxidizing agent is preferably (70-120):(35-200), more preferably (100-110):( 38-180), most preferably 109:175 or 75:38.5.
  • the mass ratio of the 2-acetyl-1,2-dihydrophenanthroline to the second organic solvent is preferably 1 g: (3-15) mL, more preferably 1 g: ( 4 to 7) mL, most preferably 1 g: 5.96 mL.
  • the present invention does not have any special limitation on the mixing, and it can be carried out by a process well known to those skilled in the art.
  • the mixing is to dissolve the 2-acetyl-1,2-dihydrophenanthroline in the second organic solvent and then add an oxidant.
  • the temperature of the oxidation reaction is preferably room temperature, and the time is preferably 5-10 hours, more preferably 6-8 hours.
  • the oxidation reaction is preferably carried out under stirring conditions, and the present invention does not have any special limitation on the rotational speed of the stirring, and the rotational speed well known to those skilled in the art can be used.
  • the present invention also preferably includes the successive steps of precipitating solids, first filtration, beating, second filtration, rinsing and drying; Water or saturated aqueous sodium bicarbonate solution is added to the obtained product system to precipitate solids.
  • the volume ratio of the water or saturated aqueous sodium bicarbonate solution to the second organic solvent is preferably 30:13 or 30:15.
  • the beating is preferably made by mixing the filter cake obtained by the first filtration with toluene and beating at a temperature of 70° C.
  • the rinsing agent used in the rinsing is preferably isopropyl ether; the drying is preferably drying; the present invention does not have any special limitation on the drying, and can be performed by a process well known to those skilled in the art.
  • the 2-acetyl-1,2-dihydrophenanthroline was dissolved in 750 mL of toluene, 110 g of peracetic acid with a mass concentration of 35% was added dropwise, stirred at room temperature for 6 hours, added to 1500 mL of water, stirred, and allowed to stand for fractionation. layer, the toluene layer was washed with water, then the temperature was raised to 70°C for beating for 30min, cooled to 5°C, filtered, rinsed and dried with isopropyl ether to obtain 61g of 2-acetyl-1,10-phenanthroline with a purity of 98.1%;
  • the 2-acetyl-1,10-phenanthroline was subjected to a nuclear magnetic test, and the test results were similar to those of Example 1.

Abstract

The present invention relates to the technical field of organic synthesis, in particular, to a preparation method for 2-acetyl-1,10-phenanthroline. The preparation method provided in the present invention comprises the following steps: in a protective atmosphere, mixing 8-aminoquinoline, 3-acetylacrolein, an acid, and a solvent, and performing an addition reaction to obtain 4-oxo-3-(quinolin-8-ylamino)pentanal; mixing 4-oxo-3-(quinolin-8-ylamino)pentanal, a catalyst, and a first organic solvent, and performing a cyclization reaction to obtain 2-acetyl-1,2-dihydrophenanthroline; and mixing the 2-acetyl-1,2-dihydrophenanthroline, an oxidant, and the second organic solvent, and performing an oxidation reaction to obtain 2-acetyl-1,10-phenanthroline. The preparation method is simple in synthesis route, mild in reaction conditions, easy in industrial production, and is green and eco-friendly in preparation raw materials.

Description

一种2-乙酰基-1,10-菲啰啉的制备方法A kind of preparation method of 2-acetyl-1,10-phenanthroline
本申请要求于2021年02月06日提交中国专利局、申请号为202110175700.4、发明名称为“一种2-乙酰基-1,10-菲啰啉的制备方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。This application claims the priority of the Chinese patent application filed on February 06, 2021, with the application number of 202110175700.4 and the invention titled "A method for the preparation of 2-acetyl-1,10-phenanthroline", The entire contents of which are incorporated herein by reference.
技术领域technical field
本发明涉及有机合成技术领域，尤其涉及一种2-乙酰基-1,10-菲啰啉的制备方法。The invention relates to the technical field of organic synthesis, in particular to a preparation method of 2-acetyl-1,10-phenanthroline.
背景技术Background technique
目前，2-乙酰基-1,10-菲啰啉主要用在光电材料，其主要是用2-溴菲啰啉在-78℃的条件下通过丁基锂拔溴，然后与N,N-二甲基乙酰胺反应制备得到。上述制备方法原料价格昂贵，合成条件太苛刻，工业化优势不大。还有报道过的工艺是先合成2-氰基-1,10-菲啰啉然后再合成2-乙酰基-1,10-菲啰啉，但是合成路线中用到了三甲基氰硅烷，毒性较大，操作复杂。At present, 2-acetyl-1,10-phenanthroline is mainly used in optoelectronic materials, which mainly uses 2-bromophenanthroline to extract bromine through butyllithium at -78 °C, and then react with N,N- Prepared by dimethylacetamide reaction. The raw materials of the above preparation method are expensive, the synthesis conditions are too harsh, and the industrialization advantage is not large. There is also a reported process of synthesizing 2-cyano-1,10-phenanthroline first and then synthesizing 2-acetyl-1,10-phenanthroline, but trimethylsilyl cyanide is used in the synthetic route, which is toxic. Large and complicated to operate.
发明内容SUMMARY OF THE INVENTION
本发明的目的在于提供一种2-乙酰基-1,10-菲啰啉的制备方法。所述制备方法合成路线简单，易于工业化生产，且原料绿色友好。The object of the present invention is to provide a preparation method of 2-acetyl-1,10-phenanthroline. The preparation method has simple synthetic route, easy industrial production, and green and friendly raw materials.
为了实现上述发明目的，本发明提供以下技术方案：In order to achieve the above-mentioned purpose of the invention, the present invention provides the following technical solutions:
本发明提供了一种2-乙酰基-1，10-菲啰啉的制备方法，包括以下步骤：The invention provides a kind of preparation method of 2-acetyl-1,10-phenanthroline, comprising the following steps:
在保护气氛中，将8-氨基喹啉、3-乙酰基丙烯醛、酸和溶剂混合，进行加成反应，得到4-氧代-3-(喹啉-8-氨基)戊醛；In a protective atmosphere, 8-aminoquinoline, 3-acetyl acrolein, an acid and a solvent are mixed to carry out an addition reaction to obtain 4-oxo-3-(quinoline-8-amino)pentanal;
将所述4-氧代-3-(喹啉-8-氨基)戊醛、催化剂和第一有机溶剂混合，进行环合反应，得到2-乙酰基-1,2-二氢菲啰啉；Mixing the 4-oxo-3-(quinoline-8-amino)pentanal, the catalyst and the first organic solvent, and carrying out a cyclization reaction to obtain 2-acetyl-1,2-dihydrophenanthroline;
将所述2-乙酰基-1,2-二氢菲啰啉、氧化剂和第二有机溶剂混合，发生氧化反应，得到所述2-乙酰基-1,10-菲啰啉。The 2-acetyl-1,2-dihydrophenanthroline, the oxidizing agent and the second organic solvent are mixed to undergo an oxidation reaction to obtain the 2-acetyl-1,10-phenanthroline.
优选的，所述8-氨基喹啉和3-乙酰基丙烯醛的摩尔比为1：(0.9～3.0)。Preferably, the molar ratio of the 8-aminoquinoline to 3-acetylacrolein is 1:(0.9-3.0).
优选的，所述酸包括有机酸或无机酸；Preferably, the acid includes an organic acid or an inorganic acid;
所述酸与所述8-氨基喹啉的质量比为100：(60～145)。The mass ratio of the acid to the 8-aminoquinoline is 100:(60-145).
优选的，所述有机酸包括醋酸、多聚磷酸、三氯氧磷、三氟乙酸和三氟甲磺酸中的一种或几种；Preferably, the organic acid includes one or more of acetic acid, polyphosphoric acid, phosphorus oxychloride, trifluoroacetic acid and trifluoromethanesulfonic acid;
所述无机酸包括盐酸、硫酸和矾酸中的一种或几种。The inorganic acid includes one or more of hydrochloric acid, sulfuric acid and vanadic acid.
优选的，所述加成反应的温度为50～65℃，时间为15～25h。Preferably, the temperature of the addition reaction is 50-65° C., and the time is 15-25 h.
优选的，所述催化剂为多聚磷酸、钒酸、浓盐酸、硫酸、三氟甲磺酸和三氟乙酸中的一种或几种；Preferably, the catalyst is one or more of polyphosphoric acid, vanadic acid, concentrated hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid and trifluoroacetic acid;
所述浓盐酸的质量浓度为30～36％。The mass concentration of the concentrated hydrochloric acid is 30-36%.
优选的，所述4-氧代-3-(喹啉-8-氨基)戊醛和催化剂的质量比为1：(0.1～10)。Preferably, the mass ratio of the 4-oxo-3-(quinoline-8-amino)pentanal to the catalyst is 1:(0.1-10).
优选的，所述环合反应的温度为77～82℃，时间为15～25h。Preferably, the temperature of the cyclization reaction is 77-82° C., and the time is 15-25 h.
优选的，所述氧化剂为四氯苯醌、二氯二氰基苯醌、高锰酸钾、双氧水、过氧叔丁醇或过氧乙酸。Preferably, the oxidant is tetrachlorobenzoquinone, dichlorodicyanobenzoquinone, potassium permanganate, hydrogen peroxide, tert-butanol peroxy or peracetic acid.
优选的，所述2-乙酰基-1,2-二氢菲啰啉和氧化剂的质量比为(70～120)：(35～200)。Preferably, the mass ratio of the 2-acetyl-1,2-dihydrophenanthroline to the oxidizing agent is (70-120): (35-200).
优选的，所述氧化反应的温度为室温，时间为5～10h。Preferably, the temperature of the oxidation reaction is room temperature, and the time is 5-10 h.
优选的，所述氧化反应完成后，还包括依次进行的析出固体、第一过滤、打浆、第二过滤、淋洗和干燥。Preferably, after the oxidation reaction is completed, the steps of solid precipitation, first filtration, pulping, second filtration, rinsing and drying are performed in sequence.
优选的，所述析出固体为在所述氧化反应完成后得到的产物体系中加入水或饱和碳酸氢钠水溶液使固体析出；Preferably, the precipitation of solid is to add water or saturated aqueous sodium bicarbonate solution to the product system obtained after the oxidation reaction is completed to precipitate the solid;
所述水或饱和碳酸氢钠水溶液与第二有机溶剂的体积比为30:13或30:15。The volume ratio of the water or saturated aqueous sodium bicarbonate solution to the second organic solvent is 30:13 or 30:15.
优选的，所述打浆为将所述第一过滤得到的滤饼与甲苯混合在70℃的温度下打浆30min。Preferably, the beating is mixing the filter cake obtained by the first filtration with toluene and beating at a temperature of 70° C. for 30 minutes.
本发明提供了一种2-乙酰基-1，10-菲啰啉的制备方法，包括以下步骤：在保护气氛中，将8-氨基喹啉、3-乙酰基丙烯醛、酸和溶剂混合，进行加成反应，得到4-氧代-3-(喹啉-8-氨基)戊醛；将所述4-氧代-3-(喹啉-8-氨基)戊醛、催化剂和第一有机溶剂混合，进行环合反应，得到2-乙酰基-1,2-二氢菲啰啉；将所述2-乙酰基-1,2-二氢菲啰啉、氧化剂和第二 有机溶剂混合，发生氧化反应，得到所述2-乙酰基-1,10-菲啰啉。所述制备方法合成路线简单，反应条件温和，易于工业化生产，且制备原料绿色友好。The invention provides a preparation method of 2-acetyl-1,10-phenanthroline, comprising the following steps: in a protective atmosphere, mixing 8-aminoquinoline, 3-acetyl acrolein, an acid and a solvent, Addition reaction is carried out to obtain 4-oxo-3-(quinoline-8-amino)pentanal; the 4-oxo-3-(quinoline-8-amino)pentanal, the catalyst and the first organic The solvent is mixed, and a cyclization reaction is carried out to obtain 2-acetyl-1,2-dihydrophenanthroline; the 2-acetyl-1,2-dihydrophenanthroline, the oxidant and the second organic solvent are mixed, An oxidation reaction occurs to give the 2-acetyl-1,10-phenanthroline. The preparation method has simple synthetic route, mild reaction conditions, easy industrial production, and green and friendly preparation raw materials.
附图说明Description of drawings
图1为实施例1制备得到的2-乙酰基-1,10-菲啰啉的核磁谱图。Fig. 1 is the nuclear magnetic spectrum of 2-acetyl-1,10-phenanthroline prepared in Example 1.
具体实施方式Detailed ways
本发明提供了一种2-乙酰基-1，10-菲啰啉的制备方法，包括以下步骤：The invention provides a kind of preparation method of 2-acetyl-1,10-phenanthroline, comprising the following steps:
在保护气氛中，将8-氨基喹啉、3-乙酰基丙烯醛、酸和溶剂混合，进行加成反应，得到4-氧代-3-(喹啉-8-氨基)戊醛；In a protective atmosphere, 8-aminoquinoline, 3-acetyl acrolein, an acid and a solvent are mixed to carry out an addition reaction to obtain 4-oxo-3-(quinoline-8-amino)pentanal;
将所述4-氧代-3-(喹啉-8-氨基)戊醛、催化剂和第一有机溶剂混合，进行环合反应，得到2-乙酰基-1,2-二氢菲啰啉；Mixing the 4-oxo-3-(quinoline-8-amino)pentanal, the catalyst and the first organic solvent, and carrying out a cyclization reaction to obtain 2-acetyl-1,2-dihydrophenanthroline;
将所述2-乙酰基-1,2-二氢菲啰啉、氧化剂和第二有机溶剂混合，发生氧化反应，得到所述2-乙酰基-1,10-菲啰啉。The 2-acetyl-1,2-dihydrophenanthroline, the oxidizing agent and the second organic solvent are mixed to undergo an oxidation reaction to obtain the 2-acetyl-1,10-phenanthroline.
在本发明中，若无特殊说明，所有制备原料均为本领域技术人员熟知的市售产品。In the present invention, unless otherwise specified, all preparation raw materials are commercially available products well known to those skilled in the art.
在本发明中，所述2-乙酰基-1,10-菲啰啉的制备流程优选如式Ⅰ所示：In the present invention, the preparation process of the 2-acetyl-1,10-phenanthroline is preferably as shown in formula I:
Figure PCTCN2021139664-appb-000001
Figure PCTCN2021139664-appb-000001
本发明在保护气氛中，将8-氨基喹啉、3-乙酰基丙烯醛、酸和溶剂混合，进行加成反应，得到4-氧代-3-(喹啉-8-氨基)戊醛。本发明对所述保护气氛没有任何特殊的限定，采用本领域技术人员熟知的非氧气氛即可。在本发明的实施例中，所述保护气氛具体为氮气气氛。In the present invention, 8-aminoquinoline, 3-acetylacrolein, acid and solvent are mixed in a protective atmosphere, and an addition reaction is carried out to obtain 4-oxo-3-(quinoline-8-amino)pentanal. The present invention does not have any special limitation on the protective atmosphere, and a non-oxygen atmosphere well-known to those skilled in the art can be used. In an embodiment of the present invention, the protective atmosphere is specifically a nitrogen atmosphere.
在本发明中，所述8-氨基喹啉的结构式为
Figure PCTCN2021139664-appb-000002
所述8-氨基喹啉优选为市售产品；所述3-乙酰基丙烯醛的结构式为
Figure PCTCN2021139664-appb-000003
所述4- 氧代-3-(喹啉-8-氨基)戊醛的结构式为
Figure PCTCN2021139664-appb-000004
In the present invention, the structural formula of the 8-aminoquinoline is
Figure PCTCN2021139664-appb-000002
The 8-aminoquinoline is preferably a commercially available product; the structural formula of the 3-acetyl acrolein is
Figure PCTCN2021139664-appb-000003
The structural formula of described 4-oxo-3-(quinoline-8-amino) pentanal is
Figure PCTCN2021139664-appb-000004
在本发明中，所述酸优选包括有机酸或无机酸；所述无机酸优选包括盐酸、硫酸和矾酸中的一种或几种；在本发明中，当所述无机酸包括盐酸时，所述盐酸优选以溶液的形式进行混合，所述盐酸的质量浓度优选为30～36％；当所述无机酸包括硫酸和/或矾酸时，所述硫酸和钒酸均优选为硫酸或钒酸的纯品。所述有机酸优选包括醋酸、多聚磷酸、三氯氧磷、三氟乙酸和三氟甲磺酸中的一种或几种。所述酸起到的是催化作用，促进所述加成反应的发生。In the present invention, the acid preferably includes an organic acid or an inorganic acid; the inorganic acid preferably includes one or more of hydrochloric acid, sulfuric acid and vanadic acid; in the present invention, when the inorganic acid includes hydrochloric acid, The hydrochloric acid is preferably mixed in the form of a solution, and the mass concentration of the hydrochloric acid is preferably 30-36%; when the inorganic acid includes sulfuric acid and/or vanadic acid, both the sulfuric acid and vanadic acid are preferably sulfuric acid or vanadium. Pure acid. The organic acid preferably includes one or more of acetic acid, polyphosphoric acid, phosphorus oxychloride, trifluoroacetic acid and trifluoromethanesulfonic acid. The acid acts as a catalyst to promote the addition reaction.
在本发明中，所述溶剂包括水和醇类有机溶剂；所述醇类有机溶剂更优选为甲醇。本发明对所述水和醇类有机溶剂的配比没有任何特殊的限定，按任意配比进行混合即可。在本发明的具体实施例中，所述醇类有机溶剂为甲醇，所述水和醇类有机溶剂的体积比为3:4和1:2。在本发明中，采用包括水和醇类有机溶剂的混合溶剂可以防止3-乙酰基丙烯醛聚合和体系的均一性，进一步提高产品收率。In the present invention, the solvent includes water and alcohol-based organic solvent; the alcohol-based organic solvent is more preferably methanol. The present invention does not have any special limitation on the ratio of the water and the alcoholic organic solvent, and can be mixed according to any ratio. In a specific embodiment of the present invention, the alcoholic organic solvent is methanol, and the volume ratio of the water to the alcoholic organic solvent is 3:4 and 1:2. In the present invention, the use of a mixed solvent including water and an alcoholic organic solvent can prevent the polymerization of 3-acetyl acrolein and the uniformity of the system, and further improve the product yield.
在本发明中，所述8-氨基喹啉和3-乙酰基丙烯醛的摩尔比优选为1：(0.9～3.0)，更优选为1：(1.5～2.5)；所述酸与所述8-氨基喹啉的质量比优选为100：(60～145)，更优选为100：(70～75)。在本发明中，所述8-氨基喹啉的质量与溶剂的体积比优选为1g：(3～20)mL，更优选为1g：(4～7)mL。In the present invention, the molar ratio of the 8-aminoquinoline and 3-acetylacrolein is preferably 1:(0.9-3.0), more preferably 1:(1.5-2.5); the acid and the 8 The mass ratio of -aminoquinoline is preferably 100:(60-145), more preferably 100:(70-75). In the present invention, the mass ratio of the 8-aminoquinoline to the solvent is preferably 1 g: (3-20) mL, more preferably 1 g: (4-7) mL.
本发明对所述混合没有任何特殊的限定，采用本领域技术人员熟知的过程进行即可。The present invention does not have any special limitation on the mixing, and it can be carried out by a process well known to those skilled in the art.
在本发明中，所述加成反应的温度优选为50～65℃，更优选为55～60℃；时间优选为15～25h，更优选为18～23h。In the present invention, the temperature of the addition reaction is preferably 50-65°C, more preferably 55-60°C; the time is preferably 15-25h, more preferably 18-23h.
在所述加成反应过程中，优选通过TLC检测所述8-氨基喹啉是否消耗完成来判断所述加成反应是否结束。In the process of the addition reaction, it is preferable to judge whether the addition reaction is finished by detecting whether the consumption of the 8-aminoquinoline is completed by TLC.
所述加成反应完成后，本发明还优选包括过滤；本发明对所述过滤没有任何特殊的限定，采用本领域技术人员熟知的过程进行即可。After the addition reaction is completed, the present invention also preferably includes filtration; the present invention does not have any special limitation on the filtration, and can be performed by a process well known to those skilled in the art.
得到4-氧代-3-(喹啉-8-氨基)戊醛后，本发明将所述4-氧代-3-(喹啉-8-氨基)戊醛、催化剂和第一有机溶剂混合，进行环合反应，得到2-乙酰基-1,2-二氢菲啰啉。After obtaining 4-oxo-3-(quinoline-8-amino)pentanal, the present invention mixes the 4-oxo-3-(quinoline-8-amino)pentanal, the catalyst and the first organic solvent , cyclization reaction was carried out to obtain 2-acetyl-1,2-dihydrophenanthroline.
在本发明中，所述催化剂优选为多聚磷酸、钒酸、浓盐酸、硫酸、三氟甲磺酸和三氟乙酸中的一种或几种，所述浓盐酸的质量浓度优选为30～36％；当所述催化剂为上述具体选择中的两种以上时，本发明对上述具体物质的配比没有任何特殊的限定，按任意配比进行混合即可。在本发明的具体实施例中，所述催化剂为多聚磷酸和钒酸；所述多聚磷酸和钒酸的质量比具体为45:1。In the present invention, the catalyst is preferably one or more of polyphosphoric acid, vanadic acid, concentrated hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid and trifluoroacetic acid, and the mass concentration of the concentrated hydrochloric acid is preferably 30～ 36%; when the catalysts are two or more of the above specific options, the present invention does not have any special restrictions on the proportion of the above specific substances, and the mixture can be carried out according to any proportion. In a specific embodiment of the present invention, the catalyst is polyphosphoric acid and vanadic acid; the mass ratio of the polyphosphoric acid and vanadic acid is specifically 45:1.
在本发明中，所述第一有机溶剂优选为乙酸乙酯、甲基叔丁基醚、甲苯、氯代烷烃和多聚磷酸中的一种或几种；当所述第一有机溶剂为上述具体选择中的两种以上时，本发明对上述具体物质的配比没有任何特殊的限定，按任意配比进行混合即可。在本发明的具体实施例中，所述第一有机溶剂为乙酸乙酯。In the present invention, the first organic solvent is preferably one or more of ethyl acetate, methyl tert-butyl ether, toluene, chlorinated alkanes and polyphosphoric acid; when the first organic solvent is the above When more than two kinds of materials are specifically selected, the present invention does not have any special limitation on the mixing ratio of the above-mentioned specific substances, and the mixture can be carried out according to any mixing ratio. In a specific embodiment of the present invention, the first organic solvent is ethyl acetate.
在本发明中，所述4-氧代-3-(喹啉-8-氨基)戊醛和催化剂的质量比优选为1：(0.1～10)，更优选为1：(0.3～1)。在本发明中，所述4-氧代-3-(喹啉-8-氨基)戊醛的质量与所述第一有机溶剂的体积比优选为1g：(3～20)mL，更优选为1g：(3～5)mL。In the present invention, the mass ratio of the 4-oxo-3-(quinoline-8-amino)pentanal to the catalyst is preferably 1:(0.1-10), more preferably 1:(0.3-1). In the present invention, the mass ratio of the 4-oxo-3-(quinoline-8-amino)pentanal to the volume of the first organic solvent is preferably 1 g: (3-20) mL, more preferably 1 g: (3 to 5) mL.
本发明对所述混合没有任何特殊的限定，采用本领域技术人员熟知的过程进行即可。The present invention does not have any special limitation on the mixing, and it can be carried out by a process well known to those skilled in the art.
在本发明中，所述环合反应的温度优选为77～82℃，更优选为80℃；时间优选为15～25h，更优选为18～22h。所述环合反应优选在回流的条件下进行。In the present invention, the temperature of the cyclization reaction is preferably 77-82°C, more preferably 80°C; the time is preferably 15-25h, more preferably 18-22h. The cyclization reaction is preferably carried out under reflux conditions.
在所述环合反应过程中，优选通过TLC检测所述3-乙酰基丙烯醛是否消耗完成来判断所述环合反应是否结束。In the process of the cyclization reaction, it is preferable to judge whether the cyclization reaction ends by detecting whether the consumption of the 3-acetylacrolein is completed by TLC.
所述环合反应完成后，本发明还优选包括依次进行的回收溶剂和采用醋酸套蒸的过程；所述回收溶剂的方式优选为减压蒸馏；所述采用醋酸套蒸的过程优选为减压蒸馏。当所述催化剂包括多聚磷酸或所述第一有机溶剂包括多聚磷酸时，所述回收溶剂前，优选包括采用碱水洗掉多聚磷酸； 本发明对所述碱水的种类没有任何特殊的限定，采用本领域技术人员熟知的种类即可。After the cyclization reaction is completed, the present invention also preferably includes the process of successively recovering the solvent and using acetic acid jacket to steam; the method of recovering the solvent is preferably reduced pressure distillation; the process of using the acetic acid jacket to steam is preferably reduced pressure. Distilled. When the catalyst includes polyphosphoric acid or the first organic solvent includes polyphosphoric acid, before recovering the solvent, it is preferable to use alkaline water to wash off the polyphosphoric acid; the present invention does not have any special type of the alkaline water. The definition of , can use the type well-known to those skilled in the art.
得到2-乙酰基-1,2-二氢菲啰啉后，本发明将所述2-乙酰基-1,2-二氢菲啰啉、氧化剂和第二有机溶剂混合，发生氧化反应，得到所述2-乙酰基-1,10-菲啰啉。After obtaining 2-acetyl-1,2-dihydrophenanthroline, the present invention mixes the 2-acetyl-1,2-dihydrophenanthroline, an oxidizing agent and a second organic solvent, and an oxidation reaction occurs to obtain The 2-acetyl-1,10-phenanthroline.
在本发明中，所述氧化剂优选为四氯苯醌、二氯二氰基苯醌、高锰酸钾、双氧水、过氧叔丁醇或过氧乙酸，更优选为四氯苯醌或过氧乙酸；当所述催化剂为过氧乙酸时，所述过氧乙酸优选以溶液的形式加入；所述过氧乙酸的质量浓度优选为35％。In the present invention, the oxidant is preferably tetrachlorobenzoquinone, dichlorodicyanobenzoquinone, potassium permanganate, hydrogen peroxide, tert-butanol peroxy or peracetic acid, more preferably tetrachlorobenzoquinone or peroxygen Acetic acid; when the catalyst is peracetic acid, the peracetic acid is preferably added in the form of a solution; the mass concentration of the peracetic acid is preferably 35%.
在本发明中，所述第二有机溶剂优选为醋酸、二氯甲烷、氯仿、二氯乙烷、甲苯或醚类溶剂，更优选为醋酸。In the present invention, the second organic solvent is preferably acetic acid, dichloromethane, chloroform, dichloroethane, toluene or an ether solvent, more preferably acetic acid.
在本发明中，所述2-乙酰基-1,2-二氢菲啰啉和氧化剂的质量比优选为(70～120)：(35～200)，更优选为(100～110)：(38～180)，最优选为109:175或75:38.5。In the present invention, the mass ratio of the 2-acetyl-1,2-dihydrophenanthroline to the oxidizing agent is preferably (70-120):(35-200), more preferably (100-110):( 38-180), most preferably 109:175 or 75:38.5.
在本发明中，所述2-乙酰基-1,2-二氢菲啰啉的质量与所述第二有机溶剂的体积比优选为1g：(3～15)mL，更优选为1g：(4～7)mL，最优选为1g：5.96mL。In the present invention, the mass ratio of the 2-acetyl-1,2-dihydrophenanthroline to the second organic solvent is preferably 1 g: (3-15) mL, more preferably 1 g: ( 4 to 7) mL, most preferably 1 g: 5.96 mL.
本发明对所述混合没有任何特殊的限定，采用本领域技术人员熟知的过程进行即可。在本发明的实施例中，所述混合为将所述2-乙酰基-1,2-二氢菲啰啉溶于第二有机溶剂后再加入氧化剂。The present invention does not have any special limitation on the mixing, and it can be carried out by a process well known to those skilled in the art. In the embodiment of the present invention, the mixing is to dissolve the 2-acetyl-1,2-dihydrophenanthroline in the second organic solvent and then add an oxidant.
在本发明中，所述氧化反应的温度优选为室温，时间优选为5～10h，更优选为6～8h。在本发明中，所述氧化反应优选在搅拌的条件下进行，本发明对所述搅拌的转速没有任何特殊的限定，采用本领域技术人员熟知的转速进行即可。In the present invention, the temperature of the oxidation reaction is preferably room temperature, and the time is preferably 5-10 hours, more preferably 6-8 hours. In the present invention, the oxidation reaction is preferably carried out under stirring conditions, and the present invention does not have any special limitation on the rotational speed of the stirring, and the rotational speed well known to those skilled in the art can be used.
所述氧化反应完成后，本发明还优选包括依次进行的析出固体、第一过滤、打浆、第二过滤、淋洗和干燥；在本发明中，所述析出固体优选为在所述氧化反应完成后得到的产物体系中加入水或饱和碳酸氢钠水溶液使固体析出。所述水或饱和碳酸氢钠水溶液与第二有机溶剂的体积比优选为30:13或30:15。本发明对所述第一过滤和第二过滤的过程没有任何特 殊的限定，采用本领域技术人员熟知的过程进行即可。在本发明中，所述打浆优选为将所述第一过滤得到的滤饼与甲苯混合在70℃的温度下打浆30min；所述甲苯与醋酸的体积比优选为20:13。所述淋洗采用的淋洗剂优选为异丙醚；所述干燥优选为烘干；本发明对所述烘干没有任何特殊的限定，采用本领域技术人员熟知的过程进行即可。After the oxidation reaction is completed, the present invention also preferably includes the successive steps of precipitating solids, first filtration, beating, second filtration, rinsing and drying; Water or saturated aqueous sodium bicarbonate solution is added to the obtained product system to precipitate solids. The volume ratio of the water or saturated aqueous sodium bicarbonate solution to the second organic solvent is preferably 30:13 or 30:15. The present invention does not have any special limitation on the process of the first filtration and the second filtration, and can be performed by using a process well known to those skilled in the art. In the present invention, the beating is preferably made by mixing the filter cake obtained by the first filtration with toluene and beating at a temperature of 70° C. for 30 minutes; the volume ratio of the toluene to the acetic acid is preferably 20:13. The rinsing agent used in the rinsing is preferably isopropyl ether; the drying is preferably drying; the present invention does not have any special limitation on the drying, and can be performed by a process well known to those skilled in the art.
下面结合实施例对本发明提供的2-乙酰基-1,10-菲啰啉的制备方法进行详细的说明，但是不能把它们理解为对本发明保护范围的限定。The preparation method of 2-acetyl-1,10-phenanthroline provided by the present invention will be described in detail below in conjunction with the examples, but they should not be construed as limiting the protection scope of the present invention.
实施例1Example 1
将72g(0.499mol)8-氨基喹啉，85g(0.867mol)3-乙酰基丙烯醛、150g水、100g醋酸和200mL甲醇混合，在氮气气氛下，升温至60℃，进行加成反应18h，过滤，得到118g 4-氧代-3-(喹啉-8-氨基)戊醛；Mix 72 g (0.499 mol) of 8-aminoquinoline, 85 g (0.867 mol) of 3-acetylacrolein, 150 g of water, 100 g of acetic acid and 200 mL of methanol, and under a nitrogen atmosphere, the temperature is raised to 60 ° C, and an addition reaction is carried out for 18 h, Filtration to obtain 118g of 4-oxo-3-(quinoline-8-amino)pentanal;
将所述4-氧代-3-(喹啉-8-氨基)戊醛在400mL乙酸乙酯中溶解后，加入45g多聚磷酸和1g钒酸，加热至回流状态(77℃)，反应20h，采用碱水洗掉多聚磷酸，减压回收溶剂，再用醋酸套蒸，得到109g 2-乙酰基-1,2-二氢菲啰啉；After the 4-oxo-3-(quinoline-8-amino)pentanal was dissolved in 400 mL of ethyl acetate, 45 g of polyphosphoric acid and 1 g of vanadic acid were added, heated to reflux (77° C.), and reacted for 20 h , the polyphosphoric acid was washed off with alkaline water, the solvent was recovered under reduced pressure, and then steamed with acetic acid to obtain 109g of 2-acetyl-1,2-dihydrophenanthroline;
将所述2-乙酰基-1,2-二氢菲啰啉在650mL醋酸中溶解后，加入175g四氯苯醌，室温搅拌6小时，加入1500mL水析出固体，过滤，用1000mL甲苯在70℃的温度下打浆30min，降温至5℃，过滤，采用异丙醚淋洗，烘干，得到87g 2-乙酰基-1,10-菲啰啉，总收率为78.3％，纯度为98.8％；After dissolving the 2-acetyl-1,2-dihydrophenanthroline in 650 mL of acetic acid, add 175 g of tetrachlorobenzoquinone, stir at room temperature for 6 hours, add 1500 mL of water to precipitate a solid, filter, and use 1000 mL of toluene at 70° C. Beating for 30min at a temperature of 100 °C, cooling to 5°C, filtering, rinsing with isopropyl ether, drying to obtain 87g of 2-acetyl-1,10-phenanthroline, the total yield was 78.3%, and the purity was 98.8%;
将所述2-乙酰基-1,10-菲啰啉进行核磁测试，测试结果如图1所示：1H NMR解谱数据是：1H NMR(400MHz,DMSO-d6)δ9.22(dd,J＝4.3,1.8Hz,1H),8.68(d,J＝8.3Hz,1H),8.56(dd,J＝8.1,1.8Hz,1H),8.30(d,J＝8.3Hz,1H),8.19–8.06(m,2H),7.85(dd,J＝8.1,4.3Hz,1H),2.92(s,3H)。The 2-acetyl-1,10-phenanthroline was subjected to nuclear magnetic test, and the test results are shown in Figure 1: 1H NMR decomposing data is: 1H NMR (400MHz, DMSO-d6) δ9.22 (dd, J =4.3,1.8Hz,1H),8.68(d,J=8.3Hz,1H),8.56(dd,J=8.1,1.8Hz,1H),8.30(d,J=8.3Hz,1H),8.19–8.06 (m, 2H), 7.85 (dd, J=8.1, 4.3 Hz, 1H), 2.92 (s, 3H).
实施例2Example 2
将72g(0.499mol)8-氨基喹啉，65g(0.66mol)3-乙酰基丙烯醛、100g水、50g质量浓度为30％的盐酸和200mL甲醇混合，在氮气气氛下，升温至65℃，进行加成反应18h，过滤，得到92g 4-氧代-3-(喹啉-8-氨基)戊醛；Mix 72g (0.499mol) 8-aminoquinoline, 65g (0.66mol) 3-acetylacrolein, 100g water, 50g hydrochloric acid with a mass concentration of 30% and 200mL methanol, under nitrogen atmosphere, heat up to 65 ℃, The addition reaction was carried out for 18h and filtered to obtain 92g of 4-oxo-3-(quinoline-8-amino)pentanal;
将所述4-氧代-3-(喹啉-8-氨基)戊醛在450mL乙酸乙酯中溶解后，加入50g多聚磷酸，加热至回流状态(77℃)，反应20h，采用碱水洗掉多聚磷酸，减压回收溶剂，再用醋酸套蒸，得到70g 2-乙酰基-1,2-二氢菲啰啉；After the 4-oxo-3-(quinoline-8-amino)pentanal was dissolved in 450 mL of ethyl acetate, 50 g of polyphosphoric acid was added, heated to a reflux state (77° C.), and reacted for 20 h, using alkaline water Polyphosphoric acid was washed off, the solvent was recovered under reduced pressure, and then steamed with acetic acid to obtain 70g of 2-acetyl-1,2-dihydrophenanthroline;
将所述2-乙酰基-1,2-二氢菲啰啉在750mL甲苯中溶解，滴加质量浓度为35％的过氧乙酸110g，室温搅拌6小时，加入到1500mL水中搅拌，静置分层，甲苯层水洗，然后升温至70℃打浆30min，降温至5℃，过滤，采用异丙醚淋洗烘干，得到61g 2-乙酰基-1,10-菲啰啉，纯度为98.1％；The 2-acetyl-1,2-dihydrophenanthroline was dissolved in 750 mL of toluene, 110 g of peracetic acid with a mass concentration of 35% was added dropwise, stirred at room temperature for 6 hours, added to 1500 mL of water, stirred, and allowed to stand for fractionation. layer, the toluene layer was washed with water, then the temperature was raised to 70°C for beating for 30min, cooled to 5°C, filtered, rinsed and dried with isopropyl ether to obtain 61g of 2-acetyl-1,10-phenanthroline with a purity of 98.1%;
将所述2-乙酰基-1,10-菲啰啉进行核磁测试，测试结果跟实施例1的结果相似。The 2-acetyl-1,10-phenanthroline was subjected to a nuclear magnetic test, and the test results were similar to those of Example 1.
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润蚀，这些改进和润湿也应视为本发明的保护范围。The above are only the preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, without departing from the principles of the present invention, several improvements and erosions can also be made. Wetness should also be considered within the scope of protection of the present invention.

Claims (14)

  1. 一种2-乙酰基-1,10-菲啰啉的制备方法，其特征在于，包括以下步骤：A preparation method of 2-acetyl-1,10-phenanthroline, is characterized in that, comprises the following steps:
    在保护气氛中，将8-氨基喹啉、3-乙酰基丙烯醛、酸和溶剂混合，进行加成反应，得到4-氧代-3-(喹啉-8-氨基)戊醛；In a protective atmosphere, 8-aminoquinoline, 3-acetyl acrolein, an acid and a solvent are mixed to carry out an addition reaction to obtain 4-oxo-3-(quinoline-8-amino)pentanal;
    将所述4-氧代-3-(喹啉-8-氨基)戊醛、催化剂和第一有机溶剂混合，进行环合反应，得到2-乙酰基-1,2-二氢菲啰啉；Mixing the 4-oxo-3-(quinoline-8-amino)pentanal, the catalyst and the first organic solvent, and carrying out a cyclization reaction to obtain 2-acetyl-1,2-dihydrophenanthroline;
    将所述2-乙酰基-1,2-二氢菲啰啉、氧化剂和第二有机溶剂混合，发生氧化反应，得到所述2-乙酰基-1,10-菲啰啉。The 2-acetyl-1,2-dihydrophenanthroline, the oxidizing agent and the second organic solvent are mixed to undergo an oxidation reaction to obtain the 2-acetyl-1,10-phenanthroline.
  2. 如权利要求1所述的制备方法，其特征在于，所述8-氨基喹啉和3-乙酰基丙烯醛的摩尔比为1：(0.9～3.0)。The preparation method according to claim 1, wherein the molar ratio of the 8-aminoquinoline and 3-acetylacrolein is 1:(0.9-3.0).
  3. 如权利要求1所述的制备方法，其特征在于，所述酸包括有机酸或无机酸；The preparation method of claim 1, wherein the acid comprises an organic acid or an inorganic acid;
    所述酸与所述8-氨基喹啉的质量比为100：(60～145)。The mass ratio of the acid to the 8-aminoquinoline is 100:(60-145).
  4. 如权利要求3所述的制备方法，其特征在于，所述有机酸包括醋酸、多聚磷酸、三氯氧磷、三氟乙酸和三氟甲磺酸中的一种或几种；The preparation method of claim 3, wherein the organic acid comprises one or more of acetic acid, polyphosphoric acid, phosphorus oxychloride, trifluoroacetic acid and trifluoromethanesulfonic acid;
    所述无机酸包括盐酸、硫酸和矾酸中的一种或几种。The inorganic acid includes one or more of hydrochloric acid, sulfuric acid and vanadic acid.
  5. 如权利要求1～4任一项所述的制备方法，其特征在于，所述加成反应的温度为50～65℃，时间为15～25h。The preparation method according to any one of claims 1 to 4, wherein the temperature of the addition reaction is 50-65° C. and the time is 15-25 h.
  6. 如权利要求1所述的制备方法，其特征在于，所述催化剂为多聚磷酸、钒酸、浓盐酸、硫酸、三氟甲磺酸和三氟乙酸中的一种或几种；The preparation method of claim 1, wherein the catalyst is one or more of polyphosphoric acid, vanadic acid, concentrated hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid and trifluoroacetic acid;
    所述浓盐酸的质量浓度为30～36％。The mass concentration of the concentrated hydrochloric acid is 30-36%.
  7. 如权利要求1或6所述的制备方法，其特征在于，所述4-氧代-3-(喹啉-8-氨基)戊醛和催化剂的质量比为1：(0.1～10)。The preparation method according to claim 1 or 6, wherein the mass ratio of the 4-oxo-3-(quinoline-8-amino)pentanal and the catalyst is 1:(0.1-10).
  8. 如权利要求7所述的制备方法，其特征在于，所述环合反应的温度为77～82℃，时间为15～25h。The preparation method according to claim 7, wherein the temperature of the cyclization reaction is 77-82°C, and the time is 15-25h.
  9. 如权利要求1所述的制备方法，其特征在于，所述氧化剂为四氯苯醌、二氯二氰基苯醌、高锰酸钾、双氧水、过氧叔丁醇或过氧乙酸。The preparation method of claim 1, wherein the oxidant is tetrachlorobenzoquinone, dichlorodicyanobenzoquinone, potassium permanganate, hydrogen peroxide, tert-butanol peroxy or peracetic acid.
  10. 如权利要求1或9所述的制备方法，其特征在于，所述2-乙酰基-1,2-二氢菲啰啉和氧化剂的质量比为(70～120)：(35～200)。The preparation method according to claim 1 or 9, wherein the mass ratio of the 2-acetyl-1,2-dihydrophenanthroline to the oxidizing agent is (70-120): (35-200).
  11. 如权利要求10所述的制备方法，其特征在于，所述氧化反应的温度为室温，时间为5～10h。The preparation method according to claim 10, wherein the temperature of the oxidation reaction is room temperature, and the time is 5-10 h.
  12. 如权利要求1所述的制备方法，其特征在于，所述氧化反应完成后，还包括依次进行的析出固体、第一过滤、打浆、第二过滤、淋洗和干燥。The preparation method according to claim 1, characterized in that, after the oxidation reaction is completed, it further comprises precipitation of solids, first filtration, beating, second filtration, rinsing and drying performed in sequence.
  13. 如权利要求12所述的制备方法，其特征在于，所述析出固体为在所述氧化反应完成后得到的产物体系中加入水或饱和碳酸氢钠水溶液使固体析出；The preparation method of claim 12, wherein the precipitated solid is to add water or a saturated aqueous sodium bicarbonate solution to the product system obtained after the oxidation reaction is completed to precipitate the solid;
    所述水或饱和碳酸氢钠水溶液与第二有机溶剂的体积比为30:13或30:15。The volume ratio of the water or saturated aqueous sodium bicarbonate solution to the second organic solvent is 30:13 or 30:15.
  14. 如权利要求12所述的制备方法，其特征在于，所述打浆为将所述第一过滤得到的滤饼与甲苯混合在70℃的温度下打浆30min。The preparation method of claim 12, wherein the beating is mixing the filter cake obtained by the first filtration with toluene and beating at a temperature of 70° C. for 30 minutes.
PCT/CN2021/139664 2021-02-06 2021-12-20 Preparation method for 2-acetyl-1,10-phenanthroline WO2022166441A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB2304953.9A GB2614199A (en) 2021-02-06 2021-12-20 Preparation method for 2-acetyl-1, 10-phenanthroline

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202110175700.4A CN112961154B (en) 2021-02-06 2021-02-06 Preparation method of 2-acetyl-1, 10-phenanthroline
CN202110175700.4 2021-02-06

Publications (1)

Publication Number Publication Date
WO2022166441A1 true WO2022166441A1 (en) 2022-08-11

Family

ID=76284364

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/139664 WO2022166441A1 (en) 2021-02-06 2021-12-20 Preparation method for 2-acetyl-1,10-phenanthroline

Country Status (3)

Country Link
CN (1) CN112961154B (en)
GB (1) GB2614199A (en)
WO (1) WO2022166441A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112961154B (en) * 2021-02-06 2022-01-28 台州市生物医化产业研究院有限公司 Preparation method of 2-acetyl-1, 10-phenanthroline
CN114773591B (en) * 2022-04-26 2023-10-13 中国科学技术大学先进技术研究院 Preparation method of polyfuran dicarboxyl butanediamine

Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB454526A (en) * 1934-12-22 1936-10-02 Nl Kininefabriek Nv Process of preparing halogenated phenanthrolines
RU2313525C1 (en) * 2006-05-04 2007-12-27 Институт нефтехимии и катализа РАН Method for preparing 2,3-dialkyl-1,10-phenanthrolines
CN101239977A (en) * 2007-02-09 2008-08-13 北京大学 Quadridentate-bridged ligand, its iridium complexes and iridium-rare earth ion bimetal complexes, and preparation method and application thereof
CN101903418A (en) * 2007-12-21 2010-12-01 巴塞尔聚烯烃股份有限公司 Phenantroline-comprising complexes
CN102485733A (en) * 2010-12-01 2012-06-06 中国石油化工股份有限公司 Preparation of acetyl-substituted-1,10-phenanthroline complex and application of prepared complex as catalyst
CN103804428A (en) * 2012-11-09 2014-05-21 中国石油化工股份有限公司 Preparation method and application of complex
CN104418915A (en) * 2013-08-23 2015-03-18 中国石油化工股份有限公司 Preparation method and application of complex
CN104418690A (en) * 2013-08-23 2015-03-18 中国石油化工股份有限公司 Method for oligomerization of ethylene
CN105153032A (en) * 2015-10-13 2015-12-16 遵义医学院 Preparation method of 6-H-phenanthridine compounds by one-pot process
CN105348281A (en) * 2015-10-31 2016-02-24 丁玉琴 Synthetic method of 2, 9-dinitro-4, 7-dimethyl-1, 10-phenanthroline
CN108290865A (en) * 2015-12-01 2018-07-17 喜星素材株式会社 Heterocyclic compound and use its organic luminescent device
CN110003203A (en) * 2019-04-11 2019-07-12 北京燕联化工技术有限公司 A kind of method of synthesis 2- acetyl group -1,10- ferrosin (3)
CN111087394A (en) * 2019-12-30 2020-05-01 西安瑞联新材料股份有限公司 Synthetic method of 2, 9-substituted 4-halo-1, 10-phenanthroline
CN112961154A (en) * 2021-02-06 2021-06-15 台州市生物医化产业研究院有限公司 Preparation method of 2-acetyl-1, 10-phenanthroline

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB450624A (en) * 1935-10-03 1936-07-22 Jacob Boeeseken Process of preparing substituted amino-m-phenanthrolines

Patent Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB454526A (en) * 1934-12-22 1936-10-02 Nl Kininefabriek Nv Process of preparing halogenated phenanthrolines
RU2313525C1 (en) * 2006-05-04 2007-12-27 Институт нефтехимии и катализа РАН Method for preparing 2,3-dialkyl-1,10-phenanthrolines
CN101239977A (en) * 2007-02-09 2008-08-13 北京大学 Quadridentate-bridged ligand, its iridium complexes and iridium-rare earth ion bimetal complexes, and preparation method and application thereof
CN101903418A (en) * 2007-12-21 2010-12-01 巴塞尔聚烯烃股份有限公司 Phenantroline-comprising complexes
CN102485733A (en) * 2010-12-01 2012-06-06 中国石油化工股份有限公司 Preparation of acetyl-substituted-1,10-phenanthroline complex and application of prepared complex as catalyst
CN103804428A (en) * 2012-11-09 2014-05-21 中国石油化工股份有限公司 Preparation method and application of complex
CN104418915A (en) * 2013-08-23 2015-03-18 中国石油化工股份有限公司 Preparation method and application of complex
CN104418690A (en) * 2013-08-23 2015-03-18 中国石油化工股份有限公司 Method for oligomerization of ethylene
CN105153032A (en) * 2015-10-13 2015-12-16 遵义医学院 Preparation method of 6-H-phenanthridine compounds by one-pot process
CN105348281A (en) * 2015-10-31 2016-02-24 丁玉琴 Synthetic method of 2, 9-dinitro-4, 7-dimethyl-1, 10-phenanthroline
CN108290865A (en) * 2015-12-01 2018-07-17 喜星素材株式会社 Heterocyclic compound and use its organic luminescent device
CN110003203A (en) * 2019-04-11 2019-07-12 北京燕联化工技术有限公司 A kind of method of synthesis 2- acetyl group -1,10- ferrosin (3)
CN111087394A (en) * 2019-12-30 2020-05-01 西安瑞联新材料股份有限公司 Synthetic method of 2, 9-substituted 4-halo-1, 10-phenanthroline
CN112961154A (en) * 2021-02-06 2021-06-15 台州市生物医化产业研究院有限公司 Preparation method of 2-acetyl-1, 10-phenanthroline

Also Published As

Publication number Publication date
GB2614199A (en) 2023-06-28
CN112961154B (en) 2022-01-28
GB202304953D0 (en) 2023-05-17
CN112961154A (en) 2021-06-15

Similar Documents

Publication Publication Date Title
WO2022166441A1 (en) Preparation method for 2-acetyl-1,10-phenanthroline
CN107434786A (en) Benzimidazole compound and preparation method thereof
CN108892669A (en) A method of preparing 2- amido-6-chloropurine
CN115368272A (en) Preparation method of 4-cyano-2-methoxybenzaldehyde
CN104262109B (en) A kind of synthetic method of resorcinol
CN111747840A (en) Preparation method of 1, 4-naphthalenedicarboxylic acid
CN115124465A (en) Preparation method of quinclorac intermediate
CN108047089B (en) Preparation method of 4-tert-butyl phthalonitrile
CN108059634B (en) The preparation method of piece spiral shell chlorins compound and its intermediate
CN105294415A (en) Preparation method of 3-halogenated fluorenone compound
CN106045942B (en) A kind of preparation method of Pramoxine HCL
CN101514161B (en) Method for preparing 2-bromo-7-nitrofluorenone
CN111675917B (en) Method for preparing solvent violet 13
CN105399703B (en) A kind of preparation method of methylene blue
CN108129363A (en) Solid phase synthesis 1- amino anthraquinones -2- sulfonic acid techniques
US20120165532A1 (en) One-Step Synthesis Method of 2,9-Dimethyl-4,7-Diphenyl-1,10- Phenanthroline
CN103923056A (en) Synthetic method of 3, 4-methylene dioxybenzaldehyde
CN109503339A (en) A kind of preparation method of meta-methoxy phenol
CN113354623B (en) Preparation method of ilaprazole key intermediate 5- (1H-pyrrole-1-yl) -2-mercaptobenzimidazole
CN110229096A (en) A kind of preparation method of 2,6- pyridinedicarboxylic acid
CN115385855B (en) Method for preparing quinclorac by two-step oxidation
CN115073364B (en) Preparation method of 6-nitropyridin-3-ol
CN112745205B (en) Preparation method of simod intermediate
US4212813A (en) Process for producing substituted or unsubstituted naphthalic acids and acid anhydrides thereof
CN106957313A (en) A kind of preparation method and purposes of heteropoly acid crystal

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21924434

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 202304953

Country of ref document: GB

Kind code of ref document: A

Free format text: PCT FILING DATE = 20211220

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21924434

Country of ref document: EP

Kind code of ref document: A1