WO2022166442A1 - 一种2-乙酰基-1,10-菲啰啉的制备方法 - Google Patents

一种2-乙酰基-1,10-菲啰啉的制备方法 Download PDF

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WO2022166442A1
WO2022166442A1 PCT/CN2021/139672 CN2021139672W WO2022166442A1 WO 2022166442 A1 WO2022166442 A1 WO 2022166442A1 CN 2021139672 W CN2021139672 W CN 2021139672W WO 2022166442 A1 WO2022166442 A1 WO 2022166442A1
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preparation
reaction
acid
imino
quinoline
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PCT/CN2021/139672
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韩得满
李运广
武承林
陈霞
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台州市生物医化产业研究院有限公司
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    • 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

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  • 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 and catalytic materials, which mainly uses 2-bromophenanthroline to extract bromine through butyllithium at -78 °C, and then react with N , N-dimethylacetamide reaction prepared.
  • the above-mentioned preparation method has expensive raw materials, too harsh synthesis conditions, and little industrialization advantage; at the same time, due to the use of trimethylsilyl cyanide in the above-mentioned preparation process, the toxicity is high, the synthesis yield is not high, and the operation is complicated.
  • 2-acetyl-1,10-phenanthroline is prepared by addition, cyclization and dehydrogenation through 3-acetyl acrolein as a raw material, but 3-acetyl acrolein is this
  • 3-acetyl acrolein is this
  • the stability of 3-acetyl acrolein is also not good, and it is not condensed. Condensation products leading to the formation of aldehydes and amino groups are easily controlled.
  • the object of the present invention is to provide a preparation method of 2-acetyl-1,10-phenanthroline.
  • the preparation method has a simple synthetic route, readily available raw materials, no solid waste, and a more environmentally friendly process.
  • the invention provides a preparation method of 2-acetyl-1,10-phenanthroline, comprising the following steps:
  • the E-1-(quinoline-8-imino) propan-2-one is mixed with absolute ethanol, and after removing moisture, a catalyst and pyruvic acid are added, and a doebner reaction occurs to obtain 2-acetylphenanthroline -4-carboxylic acid;
  • the 2-acetylphenanthroline-4-carboxylic acid is subjected to a decarboxylation reaction under alkaline conditions to obtain the 2-acetyl-1,10-phenanthroline.
  • the molar ratio of the 8-aminoquinoline to glyoxal is 1:(0.8-2.5).
  • the mass ratio of the 8-aminoquinoline to the alcoholic organic solvent is 1:(2-20).
  • the temperature of the Schiff base reaction is 40-70° C., and the time is 1-5 h.
  • the process of removing moisture is performed under reflux conditions, and the time for removing moisture is 2-3 hours.
  • the catalyst is one or more of polyphosphoric acid, vanadic acid, phosphorus oxychloride, 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 catalyst to the E-1-(quinoline-8-imino)propan-2-one is (0.01-8):1.
  • the molar ratio of the pyruvic acid to the E-1-(quinoline-8-imino)propan-2-one is (0.8-2.5):1.
  • the doebner reaction is carried out under reflux conditions, and the time of the doebner reaction is 5-20 h.
  • the pH value of the alkaline condition is 10-10.5.
  • the decarboxylation reaction is carried out under reflux conditions, and the time for the decarboxylation reaction is 8-10 h.
  • the steps of cooling, filtering, washing and drying are performed in sequence.
  • the described doebner reaction also includes the recovery of methanol and extraction that are carried out in sequence;
  • the extract used in the extraction includes purified water and dichloromethane
  • the volume ratio of the purified water and dichloromethane is 5:3.
  • the decarboxylation reaction also includes sequentially performing cooling, filtration, washing, decolorization and recrystallization.
  • the decolorization adopts activated carbon decolorization.
  • the invention provides a preparation method of 2-acetyl-1,10-phenanthroline, comprising the following steps: mixing 8-aminoquinoline, glyoxal and an alcohol organic solvent, and performing a Schiff base reaction to obtain E -1-(quinoline-8-imino)propan-2-one; Mix the E-1-(quinoline-8-imino)propan-2-one and absolute ethanol, after removing moisture , adding a catalyst and pyruvic acid, a doebner reaction occurs to obtain 2-acetylphenanthroline-4-carboxylic acid; the 2-acetylphenanthroline-4-carboxylic acid is subjected to a decarboxylation reaction under alkaline conditions to obtain the 2-Acetyl-1,10-phenanthroline.
  • the preparation method has a simple synthetic route, readily available raw materials, no solid waste, and a more environmentally friendly process.
  • 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 E-1-(quinoline-8-imino) propan-2-one is mixed with absolute ethanol, and after removing moisture, a catalyst and pyruvic acid are added, and a doebner reaction occurs to obtain 2-acetylphenanthroline -4-carboxylic acid;
  • the 2-acetylphenanthroline-4-carboxylic acid is subjected to a decarboxylation reaction under alkaline conditions 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 structural formula of the 8-aminoquinoline is The 8-aminoquinoline is preferably a commercially available product; the structural formula of the acetaldehyde is preferably The alcoholic organic solvent is preferably ethanol, methanol or isopropanol, more preferably ethanol.
  • the molar ratio of the 8-aminoquinoline to glyoxal is preferably 1:(0.8-2.5), more preferably 1:(1.0-2.0), and most preferably 1:(1.4-1.8).
  • the mass ratio of the 8-aminoquinoline to the alcoholic organic solvent is preferably 1:(2-20), more preferably 1:(6-13).
  • the temperature of the mixing is preferably room temperature, and the mixing is preferably carried out under stirring conditions.
  • the present invention does not have any special limitation on the stirring process, and the process can be carried out by a process well known to those skilled in the art. .
  • the mixing is preferably by dissolving 8-aminoquinoline in an alcoholic organic solvent, and then adding glyoxal dropwise; the present invention does not have any special limitation on the dropping process, and those skilled in the art are used. A well-known process can be performed.
  • the present invention also preferably includes a process of continuing stirring; the time for continuing stirring is preferably 1 to 10 minutes, more preferably 3 to 6 minutes.
  • the temperature of the Schiff base reaction is preferably 40-70°C, more preferably 45-60°C; the time is preferably 1-5h, more preferably 2-4h.
  • the present invention also preferably includes sequentially performing cooling, filtration, washing and drying.
  • the target temperature of the cooling is preferably -5 to 0°C, and the holding time is preferably 1 h; 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 washing preferably adopts cold ethanol to rinse the filter cake obtained by filtration.
  • the drying preferably includes suction drying and vacuum drying performed in sequence; the present invention does not have any special limitation on the suction drying, and the process can be performed by a process well known to those skilled in the art; the temperature of the vacuum drying is preferably 50-60°C, more preferably 55°C; the vacuum drying time is preferably 10h.
  • the present invention After obtaining E-1-(quinoline-8-imino)propan-2-one, the present invention combines the E-1-(quinoline-8-imino)propan-2-one and absolute ethanol After mixing and removing water, a catalyst and pyruvic acid are added, and a doebner reaction occurs to obtain 2-acetylphenanthroline-4-carboxylic acid.
  • the mass ratio of the E-1-(quinoline-8-imino)propan-2-one to the volume of absolute ethanol is preferably 1 g: (2-15) mL, more preferably 1 g : (5-12) mL.
  • the process of removing moisture is preferably performed under reflux conditions, and the time for removing moisture is preferably 2-3 hours.
  • the catalyst is preferably one or more of polyphosphoric acid (PPA), vanadic acid, phosphorus oxychloride, concentrated hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid and trifluoroacetic acid; the concentrated The mass concentration of hydrochloric acid is preferably 30-36%; when the catalyst is two or more substances in the above-mentioned specific selection, the present invention does not have any special restrictions on the ratio of the specific substances, and the mixture is carried out according to any ratio. Can.
  • the catalyst is specifically PPA and vanadic acid; the mass ratio of the PPA and vanadic acid is 46:1.
  • the pyruvic acid is preferably added by dropwise addition; the present invention does not have any special limitation on the dropwise addition process, and can be performed by a process well known to those skilled in the art.
  • the mass ratio of the catalyst to the E-1-(quinoline-8-imino)propan-2-one is preferably (0.01-8):1, more preferably (0.3-2 ):1.
  • the molar ratio of the pyruvic acid to the E-1-(quinoline-8-imino)propan-2-one is preferably (0.8 ⁇ 2.5):1, more preferably (1.04 ⁇ 1.2): 1.
  • the doebner reaction is preferably carried out under reflux conditions, and the time of the doebner reaction is preferably 5-20 hours, more preferably 10-16 hours, and most preferably 12-14 hours.
  • the described doebner reaction also preferably includes the recovery of methanol and extraction that are carried out in turn; the present invention does not have any special restrictions on the process of the recovery of methanol, and can be carried out by using a process well known to those skilled in the art; the extraction is preferably The extract is added to the product solution obtained by the doebner reaction, and after stirring for 2-3 hours, the layers are left to stand, and the obtained organic layer is washed with water.
  • the extraction solution preferably includes purified water and dichloromethane; the volume ratio of the purified water and dichloromethane is preferably 5:3; the volume ratio of the extraction solution to the absolute ethanol is preferably 8:5.
  • the present invention decarboxylates the 2-acetylphenanthroline-4-carboxylic acid under alkaline conditions to obtain the 2-acetyl-1,10 -Phenanthroline.
  • the pH value of the alkaline condition is preferably 10-10.5; the pH value is preferably adjusted by using lye solution, the invention does not have any special limitation on the type of the lye solution, and the technology in the art is used. Kinds that people are familiar with.
  • the alkali solution is a sodium hydroxide solution with a mass concentration of 10%.
  • the pH of the 2-acetylphenanthroline-4-carboxylic acid is adjusted by the alkali solution, it is preferable to select the aqueous layer by layers to carry out the subsequent decarboxylation reaction.
  • the decarboxylation reaction is preferably carried out under reflux conditions, and the time for the decarboxylation reaction is preferably 8-10 h.
  • the present invention also preferably includes sequentially performing cooling, filtration, water washing, decolorization and recrystallization.
  • the target temperature of the cooling is preferably (0 ⁇ 5) ⁇ 3°C, and the temperature is preferably kept for 1.5h after the cooling.
  • a well-known process can be performed.
  • the water washing mother liquor obtained after the water washing is completed can be directly used for the next batch of water washing process.
  • the decolorization is preferably performed by mixing the product obtained after washing with dehydrated ethanol, and then using activated carbon for decolorization; the present invention does not have any special restrictions on the amount of the dehydrated ethanol and activated carbon. Dosages that are well known to personnel. The present invention does not have any special limitation on the process of the recrystallization, and can be carried out by a process well known to those skilled in the art.
  • the crude product was obtained by filtration and washing, and the mother liquor after washing was directly used in the washing process of the next batch, and then the solid after washing was dissolved with 200 mL of absolute ethanol, and activated carbon was used to decolorize and recrystallize to obtain 46.3 g of 2-acetyl- 1,10-phenanthroline, the total yield is 83%, and the purity is 98.9%;
  • the 2-acetyl-1,10-phenanthroline was subjected to nuclear magnetic test, and the test results were similar to those of Example 1.

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Abstract

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。本发明提供的制备方法，包括以下步骤：将8-氨基喹啉、丙酮醛和醇类有机溶剂混合，发生席夫碱反应，得到E-1-(喹啉-8-亚胺基)丙烷-2-酮；将所述E-1-(喹啉-8-亚胺基)丙烷-2-酮和无水乙醇混合，去除水分后，加入催化剂和丙酮酸，发生doebner反应，得到2-乙酰基菲啰啉-4-甲酸；将所述2-乙酰基菲啰啉-4-甲酸在碱性条件下发生脱羧反应，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。

Description

一种2-乙酰基-1,10-菲啰啉的制备方法
本申请要求于2021年02月06日提交中国专利局、申请号为202110165277.X、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。
技术领域
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。
背景技术
目前，2-乙酰基-1,10-菲啰啉主要用在光电材料和催化材料，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；同时，在上述制备过程中由于用到了三甲基氰硅烷，毒性较大，合成收率也不高，操作复杂。
同时，现有技术中还有通过3-乙酰基丙烯醛作为原料通过加成、环合和脱氢制备得到2-乙酰基-1,10-菲啰啉，但是3-乙酰基丙烯醛这种原料目前还没有工业化的生产厂家(虽然可以从市售产品中买到，但是存储条件要求高，并未实现大量工业化生产)，而且3-乙酰基丙烯醛的稳定性也不好，缩合时不容易控制导致生成醛和氨基的缩合产物。
发明内容
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，原料易得，不产生固废，工艺更环保。
为了实现上述发明目的，本发明提供以下技术方案：
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：
将8-氨基喹啉、丙酮醛和醇类有机溶剂混合，发生席夫碱反应，得到E-1-(喹啉-8-亚胺基)丙烷-2-酮；
将所述E-1-(喹啉-8-亚胺基)丙烷-2-酮和无水乙醇混合，去除水分后，加入催化剂和丙酮酸，发生doebner反应，得到2-乙酰基菲啰啉-4-甲酸；
将所述2-乙酰基菲啰啉-4-甲酸在碱性条件下发生脱羧反应，得到所述2-乙酰基-1,10-菲啰啉。
优选的，所述8-氨基喹啉和丙酮醛的摩尔比为1：(0.8～2.5)。
优选的，所述8-氨基喹啉与醇类有机溶剂的质量比为1：(2～20)。
优选的，所述席夫碱反应的温度为40～70℃，时间为1～5h。
优选的，所述去除水分的过程在回流条件下进行，所述去除水分的时间为2～3h。
优选的，所述催化剂为多聚磷酸、钒酸、三氯氧磷、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为30～36％。
优选的，所述催化剂与所述E-1-(喹啉-8-亚胺基)丙烷-2-酮的质量比为(0.01～8)：1。
优选的，所述丙酮酸与所述E-1-(喹啉-8-亚胺基)丙烷-2-酮的摩尔比为(0.8～2.5)：1。
优选的，所述doebner反应在回流条件下进行，所述doebner反应的时间为5～20h。
优选的，所述碱性条件的pH值为10～10.5。
优选的，所述脱羧反应在回流条件下进行，所述脱羧反应的时间为8～10h。
优选的，所述席夫碱反应完成后，还包括依次进行的降温、过滤、洗涤和干燥。
优选的，所述doebner反应完成后，还包括依次进行的回收甲醇和萃取；
所述萃取采用的萃取液包括纯化水和二氯甲烷；
所述纯化水和二氯甲烷的体积比为5:3。
优选的，所述脱羧反应完成后，还包括依次进行的降温、过滤、水洗、脱色和重结晶。
优选的，所述脱色采用活性炭脱色。
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： 将8-氨基喹啉、丙酮醛和醇类有机溶剂混合，发生席夫碱反应，得到E-1-(喹啉-8-亚胺基)丙烷-2-酮；将所述E-1-(喹啉-8-亚胺基)丙烷-2-酮和无水乙醇混合，去除水分后，加入催化剂和丙酮酸，发生doebner反应，得到2-乙酰基菲啰啉-4-甲酸；将所述2-乙酰基菲啰啉-4-甲酸在碱性条件下发生脱羧反应，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，原料易得，不产生固废，工艺更环保。
附图说明
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。
具体实施方式
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：
将8-氨基喹啉、丙酮醛和醇类有机溶剂混合，发生席夫碱反应，得到E-1-(喹啉-8-亚胺基)丙烷-2-酮；
将所述E-1-(喹啉-8-亚胺基)丙烷-2-酮和无水乙醇混合，去除水分后，加入催化剂和丙酮酸，发生doebner反应，得到2-乙酰基菲啰啉-4-甲酸；
将所述2-乙酰基菲啰啉-4-甲酸在碱性条件下发生脱羧反应，得到所述2-乙酰基-1,10-菲啰啉。
在本发明中，若无特殊说明，所有原料组分均为本领域技术人员熟知的市售产品。
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：
Figure PCTCN2021139672-appb-000001
本发明将8-氨基喹啉、丙酮醛和醇类有机溶剂混合，发生席夫碱反应，得到E-1-(喹啉-8-亚胺基)丙烷-2-酮。
在本发明中，所述8-氨基喹啉的结构式为
Figure PCTCN2021139672-appb-000002
所述8-氨基喹 啉优选为市售产品；所述丙酮醛的结构式优选为
Figure PCTCN2021139672-appb-000003
所述醇类有机溶剂优选为乙醇、甲醇或异丙醇，更优选为乙醇。
在本发明中，所述8-氨基喹啉和丙酮醛的摩尔比优选为1：(0.8～2.5)，更优选为1：(1.0～2.0)，最优选为1：(1.4～1.8)。
在本发明中，所述8-氨基喹啉与醇类有机溶剂的质量比优选为1：(2～20)，更优选为1：(6～13)。
在本发明中，所述混合的温度优选为室温，所述混合优选在搅拌的条件下进行，本发明对所述搅拌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，所述混合优选为将8-氨基喹啉溶解在醇类有机溶剂中后，滴加丙酮醛；本发明对所述滴加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。所述滴加完成后，本发明还优选包括继续搅拌的过程；所述继续搅拌的时间优选为1～10min，更优选为3～6min。
在本发明中，所述席夫碱反应的温度优选为40～70℃，更优选为45～60℃；时间优选为1～5h，更优选为2～4h。
在本发明中，所述E-1-(喹啉-8-亚胺基)丙烷-2-酮的结构式为：
Figure PCTCN2021139672-appb-000004
所述席夫碱反应完成后，本发明还优选包括依次进行的降温、过滤、洗涤和干燥。在本发明中，所述降温的目标温度优选为-5～0℃，保温时间优选为1h；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。在本发明中，所述洗涤优选为采用冷乙醇对过滤得到的滤饼进行淋洗。在本发明中，所述干燥优选包括依次进行的抽干和真空干燥；本发明对抽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；所述真空干燥的温度优选为50～60℃，更优选为55℃；所述真空干燥的时间优选为10h。
得到E-1-(喹啉-8-亚胺基)丙烷-2-酮后，本发明将所述E-1-(喹啉-8-亚胺基)丙烷-2-酮和无水乙醇混合，去除水分后，加入催化剂和丙酮酸，发生doebner反应，得到2-乙酰基菲啰啉-4-甲酸。
在本发明中，所述E-1-(喹啉-8-亚胺基)丙烷-2-酮的质量和无水乙醇的体积比优选为1g：(2～15)mL，更优选为1g：(5～12)mL。
在本发明中，所述去除水分的过程优选在回流条件下进行，所述去除水分的时间优选为2～3h。
在本发明中，所述催化剂优选为多聚磷酸(PPA)、钒酸、三氯氧磷、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物质时，本发明对所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，所述催化剂具体为PPA和钒酸；所述PPA和钒酸的质量比为46:1。
在本发明中，所述丙酮酸优选通过滴加的方式加入；本发明对所述滴加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，所述催化剂与所述E-1-(喹啉-8-亚胺基)丙烷-2-酮的质量比优选为(0.01～8)：1，更优选为(0.3～2)：1。
在本发明中，所述丙酮酸与所述E-1-(喹啉-8-亚胺基)丙烷-2-酮的摩尔比优选为(0.8～2.5)：1，更优选为(1.04～1.2)：1。
在本发明中，所述doebner反应优选在回流条件下进行，所述doebner反应的时间优选为5～20h，更优选为10～16h，最优选为12～14h。
所述doebner反应完成后，还优选包括依次进行的回收甲醇和萃取；本发明对所述回收甲醇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；所述萃取优选为在所述doebner反应得到的产物溶液中加入萃取液，搅拌2～3h后，静置分层，将得到的有机层进行水洗。在本发明中，所述萃取液优选包括纯化水和二氯甲烷；所述纯化水和二氯甲烷的体积比优选为5:3；所述萃取液与所述无水乙醇的体积比优选为8:5。在本发明中，所述搅拌的温度优选为室温，本发明对搅拌的转速没 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；本发明对所述水洗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将所述有机层洗至pH＝6～7的范围内即可。
得到2-乙酰基菲啰啉-4-甲酸后，本发明将所述2-乙酰基菲啰啉-4-甲酸在碱性条件下发生脱羧反应，得到所述2-乙酰基-1,10-菲啰啉。
在本发明中，所述碱性条件的pH值优选为10～10.5；所述pH值优选通过采用碱液进行调节，本发明对所述碱液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。在本发明中的具体实施例中，所述碱液为质量浓度为10％的氢氧化钠溶液。
在本发明中，当所述2-乙酰基菲啰啉-4-甲酸通过碱液进行pH调节后，优选通过分层选取水层进行后续的脱羧反应。
在本发明中，所述脱羧反应优选在回流条件下进行，所述脱羧反应的时间优选为8～10h。
在所述脱羧反应的过程中，会有固体生成，优选通过TLC检测来判断反应是否完全；所述检测的过程优选为：取样，调节取样的pH＝4后，用二氯甲烷提取样品，然后对二氯甲烷层进行TLC中控，看看原料是否反应完全。
所述脱羧反应完成后，本发明还优选包括依次进行的降温、过滤、水洗、脱色和重结晶。在本发明中，所述降温的目标温度优选为(0～5)±3℃，所述降温后优选保温1.5h；本发明对所述过滤和水洗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。所述水洗完成后得到的水洗母液可直接用于下一批次的水洗过程。
在本发明中，所述脱色优选为将水洗后得到的产物与无水乙醇混合后，采用活性炭进行脱色；本发明对所述无水乙醇和活性炭的用量没有任何特殊的限定，采用本领域技术人员熟知的用量即可。本发明对所述重结晶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。
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。
实施例1
在室温下，将36g(0.25mol)8-氨基喹啉溶解在180mL的乙醇中，滴加20g(0.28mol)丙酮醛后，搅拌3min，在55℃下反应2h，降温至-5℃，保温1h，过滤，将得到的滤饼采用冷乙醇进行淋洗，抽干，在55℃下真空干燥10h，得到50.2g E-1-(喹啉-8-亚胺基)丙烷-2-酮(收率95％，纯度98％)；
将50g(0.25mol)E-1-(喹啉-8-亚胺基)丙烷-2-酮和250mL无水甲醇混合后，回流3h，再加入23gPPA和0.5g钒酸后，滴加23g(0.26mol)丙酮酸，加热回流12h，回收甲醇，加入250mL纯化水和150mL二氯甲烷，室温搅拌2h，静置分层，取有机层用水洗至pH＝7，得到2-乙酰基菲啰啉-4-甲酸；
将所述2-乙酰基菲啰啉-4-甲酸用质量浓度为10％的氢氧化钠溶液调节pH至10.5，分层，将水层进行回流9h(在回流过程中会有固体生成，取样，并调节pH＝4后，用二氯甲烷提取，二氯甲烷层进行TLC检测至所述2-乙酰基菲啰啉-4-甲酸完全消失)，降温至5±3℃，保温1.5h，过滤水洗得到粗品，水洗后的母液直接用于下一批次的水洗过程，然后用200mL的无水乙醇将水洗后的固体溶解，并采用活性炭进行脱色，重结晶，得到46.3g2-乙酰基-1,10-菲啰啉，总收率为83％，纯度为98.9％；
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：1HNMR解谱数据是：1HNMR(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),8.15(d,J＝8.8Hz,1H),8.09(d,J＝8.8Hz,1H),7.85(dd,J＝8.1,4.3Hz,1H),2.92(s,3H)。
实施例2
在室温下，将36g(0.25mol)8-氨基喹啉溶解在180mL的乙醇中，滴加20g(0.28mol)丙酮醛后，搅拌3min，在70℃下反应2h，降温至-5℃，保温1h，过滤，将得到的滤饼采用冷乙醇进行淋洗，抽干，在55℃下真空干燥10h，得到49g E-1-(喹啉-8-亚胺基)丙烷-2-酮；
将40g(0.20mol)E-1-(喹啉-8-亚胺基)丙烷-2-酮和220mL无水甲醇混合后，回流3h，再加入35g三氯氧磷，滴加21g(0.24mol)丙酮酸，加热回流15h，回收甲醇，加入到200mL纯化水和150mL二氯甲烷的混合液中，室温搅拌2h，静置分层，取有机层用水洗至pH＝7，得到2-乙酰基菲啰啉-4-甲酸；
将所述2-乙酰基菲啰啉-4-甲酸用质量浓度为10％的氢氧化钠溶液调节pH至10.5，分层，将水层进行回流15h(在回流过程中会有固体生成，取样，并调节pH＝4后，用二氯甲烷提取样品后，二氯甲烷层进行TLC检测至所述2-乙酰基菲啰啉-4-甲酸完全消失)，降温至0℃，保温1.5h，过滤水洗得到粗品，然后用200mL的无水乙醇将水洗后的固体溶解，并采用活性炭进行脱色，重结晶，得到30g 2-乙酰基-1,10-菲啰啉，纯度98.3％；
将所述2-乙酰基-1,10-菲啰啉进行核磁测试，测试结果与实施例1的结果相似。
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饰，这些改进和润饰也应视为本发明的保护范围。

Claims (15)

  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：
    将8-氨基喹啉、丙酮醛和醇类有机溶剂混合，发生席夫碱反应，得到E-1-(喹啉-8-亚胺基)丙烷-2-酮；
    将所述E-1-(喹啉-8-亚胺基)丙烷-2-酮和无水乙醇混合，去除水分后，加入催化剂和丙酮酸，发生doebner反应，得到2-乙酰基菲啰啉-4-甲酸；
    将所述2-乙酰基菲啰啉-4-甲酸在碱性条件下发生脱羧反应，得到所述2-乙酰基-1,10-菲啰啉。
  2. 如权利要求1所述的制备方法，其特征在于，所述8-氨基喹啉和丙酮醛的摩尔比为1：(0.8～2.5)。
  3. 如权利要求1所述的制备方法，其特征在于，所述8-氨基喹啉与醇类有机溶剂的质量比为1：(2～20)。
  4. 如权利要求1、2或3所述的制备方法，其特征在于，所述席夫碱反应的温度为40～70℃，时间为1～5h。
  5. 如权利要求1所述的制备方法，其特征在于，所述去除水分的过程在回流条件下进行，所述去除水分的时间为2～3h。
  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、三氯氧磷、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为30～36％。
  7. 如权利要求6所述的制备方法，其特征在于，所述催化剂与所述E-1-(喹啉-8-亚胺基)丙烷-2-酮的质量比为(0.01～8)：1。
  8. 如权利要求1所述的制备方法，其特征在于，所述丙酮酸与所述E-1-(喹啉-8-亚胺基)丙烷-2-酮的摩尔比为(0.8～2.5)：1。
  9. 如权利要求1或5～8任一项所述的制备方法，其特征在于，所述 doebner反应在回流条件下进行，所述doebner反应的时间为5～20h。
  10. 如权利要求1所述的制备方法，其特征在于，所述碱性条件的pH值为10～10.5。
  11. 如权利要求1或10所述的制备方法，其特征在于，所述脱羧反应在回流条件下进行，所述脱羧反应的时间为8～10h。
  12. 如权利要求1所述的制备方法，其特征在于，所述席夫碱反应完成后，还包括依次进行的降温、过滤、洗涤和干燥。
  13. 如权利要求1所述的制备方法，其特征在于，所述doebner反应完成后，还包括依次进行的回收甲醇和萃取；
    所述萃取采用的萃取液包括纯化水和二氯甲烷；
    所述纯化水和二氯甲烷的体积比为5:3。
  14. 如权利要求1所述的制备方法，其特征在于，所述脱羧反应完成后，还包括依次进行的降温、过滤、水洗、脱色和重结晶。
  15. 如权利要求14所述的制备方法，其特征在于，所述脱色采用活性炭脱色。
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