WO2018121050A1 - 一种3-氰基-4-羟基苯甲酸甲酯的制备方法 - Google Patents
一种3-氰基-4-羟基苯甲酸甲酯的制备方法 Download PDFInfo
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- WO2018121050A1 WO2018121050A1 PCT/CN2017/109092 CN2017109092W WO2018121050A1 WO 2018121050 A1 WO2018121050 A1 WO 2018121050A1 CN 2017109092 W CN2017109092 W CN 2017109092W WO 2018121050 A1 WO2018121050 A1 WO 2018121050A1
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- hydroxybenzoate
- cyano
- several times
- methyl
- filtered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
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- the invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of methyl 3-cyano-4-hydroxybenzoate.
- the relatively large defect of this process lies in the use of cyanide cyanide in the process of the process, which has a relatively large hazard in the actual market.
- the technical proposal of the present invention is to design a method for preparing methyl 3-cyano-4-hydroxybenzoate, which comprises the following steps:
- Methylparaben was added with magnesium chloride, triethylamine, paraformaldehyde, dichloromethane, and heated in an oil bath at 60 ° C overnight. After cooling to room temperature, the aqueous solution diluted with concentrated hydrochloric acid was slowly added, and the insoluble material was filtered off, extracted with DCM several times, dried over sodium sulfate, and filtered and dried to give methyl 3- aldehyde hydroxy-4-hydroxybenzoate;
- the advantages and advantageous effects of the present invention are as follows: 1) avoiding the use of cuprous cyanide which is highly toxic cyanide in the prior art, More suitable for industrialization; 2) Preparation of cyano group from aldehyde group, efficient and direct, suitable for mass production; 3) All raw materials are cheap and easy to obtain, and the cost advantage is obvious.
- Figure 1 is a flow chart of the present invention.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种3-氰基-4-羟基苯甲酸甲酯的制备方法,第一步,对羟基苯甲酸甲酯制备3-醛基-4-羟基苯甲酸甲酯;第二步,3-醛基-4-羟基苯甲酸甲酯制备3-氰基-4-羟基苯甲酸甲酯。本发明一种3-氰基-4-羟基苯甲酸甲酯的制备方法的优势有:1)避免了使用以前工艺中剧毒氰化物的氰化亚铜,更加适合工业化;2)由醛基制备氰基,高效直接,适合大量生产;3)所有原料便宜易得,成本优势明显。
Description
本发明属于有机合成技术领域,尤其是涉及一种3-氰基-4-羟基苯甲酸甲酯的制备方法。
制备3-氰基-4-羟基苯甲酸甲酯的传统工艺如下:
该工艺存在的比较大的缺陷在于工艺过程中采用了剧毒氰化物的氰化亚铜,在实际市场中有比较大的危害性。
发明内容
本发明的目的在于提供一种3-氰基-4-羟基苯甲酸甲酯的制备方法,旨在解决上述问题。
为了实现上述目的,本发明的技术方案是设计一种3-氰基-4-羟基苯甲酸甲酯的制备方法,包括如下步骤:
1)对羟基苯甲酸甲酯中加入氯化镁、三乙胺、多聚甲醛、二氯甲烷,油浴加热60℃过夜。冷却至室温后,慢慢加入浓盐酸稀释的水溶液,滤掉不溶物,DCM萃取若干次,硫酸钠干燥,过滤旋干,获得3-醛基-4-羟基苯甲酸甲酯;
2)将上一步骤中获得的3-醛基-4-羟基苯甲酸甲酯以及盐酸羟胺、乙腈/N,N-二甲基甲酰胺加入乙酰氯,80℃加热搅拌2小时。冷却至室温后,加入EA,水洗若干次,水相反萃取若干次,合并有有机层,硫酸钠干燥,过滤,旋至半干,析出固体,抽滤,EA洗若干次,得到粉红色粗品,抽滤,二氯甲烷洗若干次,得粉红色固体,即为3-氰基-4-羟基苯甲酸甲酯;
本发明的优点和有益效果在于:本发明一种3-氰基-4-羟基苯甲酸甲酯的制备方法的优势有:1)避免了使用以前工艺中剧毒氰化物的氰化亚铜,更加适合工业化;2)由醛基制备氰基,高效直接,适合大量生产;3)所有原料便宜易得,成本优势明显。
图1为本发明的流程图。
下面结合附图和实施例,对本发明的具体实施方式作进一步描述。以下实施例仅用于更加清楚地说明本发明的技术方案,而不能以此来限制本发明的保护范围。
实施例:
1)50L反应壶中加入,4-羟基苯甲酸甲酯(2.5kg,16.4mol),氯化镁(3.2kg,32.8mol),三乙胺(9.3L,82mol),多聚甲醛(3.9kg,131.2mol),二氯甲烷(18L),油浴60℃加热(内温44℃)过夜。冷却至室温后,慢慢加入5L浓盐酸稀释的水溶液,滤掉不溶物,DCM萃取4次,硫酸钠干燥,过滤旋干。直接下一步反应。
2)50L反应壶中加入上一步原料,盐酸羟胺(1.14kg)和乙腈/N,N-二甲基甲酰胺(10L/2.5L),加入乙酰氯(1.17L),80℃加热搅拌2小时。冷却至室温后,加入EA10L,5L水洗两次,水相反萃取一次,合并有机层,硫酸钠干燥,过滤,旋至大半干,析出大量固体,直接抽滤,EA洗两次,得到粉红色粗品,抽滤,二氯甲烷(混合少量乙酸乙酯)洗2次,得到粉红色固体1215g纯品,两步收率42%。
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,在不脱离本发明技术原理的前提下,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 (1)
- 一种3-氰基-4-羟基苯甲酸甲酯的制备方法,其特征在于,包括如下步骤:1)对羟基苯甲酸甲酯中加入氯化镁、三乙胺、多聚甲醛、二氯甲烷,油浴加热60℃过夜。冷却至室温后,慢慢加入浓盐酸稀释的水溶液,滤掉不溶物,DCM萃取若干次,硫酸钠干燥,过滤旋干,获得3-醛基-4-羟基苯甲酸甲酯;2)将上一步骤中获得的3-醛基-4-羟基苯甲酸甲酯以及盐酸羟胺、乙腈/N,N-二甲基甲酰胺加入乙酰氯,80℃加热搅拌2小时。冷却至室温后,加入EA,水洗若干次,水相反萃取若干次,合并有有机层,硫酸钠干燥,过滤,旋至半干,析出固体,抽滤,EA洗若干次,得到粉红色粗品,抽滤,二氯甲烷洗若干次,得粉红色固体,即为3-氰基-4-羟基苯甲酸甲酯;
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