WO2021218073A1 - Procédé de préparation de benzimidazolone dans un solvant aqueux - Google Patents

Procédé de préparation de benzimidazolone dans un solvant aqueux Download PDF

Info

Publication number
WO2021218073A1
WO2021218073A1 PCT/CN2020/123236 CN2020123236W WO2021218073A1 WO 2021218073 A1 WO2021218073 A1 WO 2021218073A1 CN 2020123236 W CN2020123236 W CN 2020123236W WO 2021218073 A1 WO2021218073 A1 WO 2021218073A1
Authority
WO
WIPO (PCT)
Prior art keywords
auxiliary agent
reaction
water
aqueous solution
benzimidazolone
Prior art date
Application number
PCT/CN2020/123236
Other languages
English (en)
Chinese (zh)
Inventor
张国辉
姜福元
张翠翠
付德修
王磊
侯绪会
王亮亮
Original Assignee
山东汇海医药化工有限公司
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 山东汇海医药化工有限公司 filed Critical 山东汇海医药化工有限公司
Publication of WO2021218073A1 publication Critical patent/WO2021218073A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/26—Oxygen atoms

Definitions

  • the invention belongs to the field of processing by-products of biological polypeptide condensation agents, and specifically relates to a method for preparing benzimidazolones in an aqueous solvent.
  • Benzimidazolones are important organic intermediates, especially in the fields of medicine, pigments and pesticides.
  • the organic solvent used is harmful to the human body, and the process is complicated with a large amount of waste liquid;
  • the purpose of the present invention is to overcome the problems of poor safety, low yield, high production cost, etc., which are common in the prior art, and provide a method for preparing benzimidazolones in an aqueous solvent.
  • the technical solution adopted by the present invention to solve its technical problem is: a method for preparing benzimidazolone in a water solvent, including the following steps: adding an auxiliary agent aqueous solution to a reaction flask, turning on the stirring, and adding when the temperature reaches 90-140°C O-phenylenediamine and urea are incubated and reacted for 3-8h. After the reaction is completed, the auxiliary aqueous solution or mother liquor is added, filtered with suction and rinsed with water. The solid material is benzimidazolone, the mother liquor is used, and the eluent is concentrated and then used.
  • the mass ratio of the auxiliary agent to water in the auxiliary agent aqueous solution is 1-2:1-20.
  • the auxiliary agent is one or more of sodium salt, magnesium salt, aluminum salt, potassium salt, calcium salt, iron salt, copper salt, and zinc salt.
  • the mass ratio of urea to o-phenylenediamine is 1:1.3-1:1.
  • the mass ratio of the o-phenylenediamine to the water initially added to the auxiliary agent aqueous solution in the reaction flask is 1-2:1-5.
  • the temperature for adding o-phenylenediamine and urea is preferably 105-130°C.
  • the reaction route of the present invention is as follows:
  • the present invention has the following beneficial effects: the present invention selects urea and o-phenylenediamine to react to prepare benzimidazolones, uses urea as a cyclization agent, and the reproduced ammonia can be easily absorbed and utilized; the addition of auxiliary agents can effectively increase the boiling point of water and make the reaction The temperature in the process reaches the temperature of the condensation reaction of o-phenylenediamine and urea to promote the reaction.
  • the auxiliary agent selected by the invention is safe and environmentally friendly, low in price and easy to obtain.
  • the mother liquor after the reaction can also be recycled and reused without multiple addition of additives, saving material costs; the reaction materials are carried out in a homogeneous reaction system, and the reaction materials are fully mixed; the solvent water is used multiple times to achieve green synthesis and product yield Up to 99%, the purity is greater than 99.0%.
  • auxiliary agent aqueous solution Add the auxiliary agent aqueous solution to the reaction flask.
  • the auxiliary agent is sodium salt.
  • the mass ratio of auxiliary agent to water in the auxiliary agent aqueous solution is 1:8.
  • the mass ratio of phenylenediamine is 1:1.1, the mass ratio of o-phenylenediamine to the water initially added to the auxiliary agent aqueous solution in the reaction flask is 2:5, and the reaction is kept at 130°C for 5 hours.
  • auxiliary agent aqueous solution 14 After the reaction is completed, add auxiliary agent aqueous solution 14 , Suction filtration and rinsing with water, the filter cake is dried into benzimidazolone, the filtrate is the mother liquor after being concentrated, the benzimidazolone yield is 99.04%, and the purity is 99.32%.
  • auxiliary agent aqueous solution Add the auxiliary agent aqueous solution to the reaction flask.
  • the auxiliary agent is magnesium salt.
  • the mass ratio of auxiliary agent to water in the auxiliary agent aqueous solution is 2:15.
  • the mass ratio of phenylenediamine is 1:1, the mass ratio of o-phenylenediamine to the water initially added to the auxiliary agent aqueous solution in the reaction flask is 1:3, and the reaction is kept at 105°C for 3 hours.
  • the auxiliary agent aqueous solution is added. Suction filtration and rinsing with water, the filter cake is dried into benzimidazolone, the filtrate is the mother liquor after being concentrated, the yield of benzimidazolone is 99.19%, and the purity is 99.61%.
  • the auxiliary agent is a mixture of aluminum salt and zinc salt
  • the mass ratio of auxiliary agent to water in the auxiliary agent aqueous solution is 1.1:20
  • turn on the stirring and add o-phenylenediamine
  • the mass ratio of urea, urea and o-phenylenediamine is 1:1.2
  • the mass ratio of o-phenylenediamine to the water initially added to the auxiliary agent aqueous solution in the reaction flask is 1:4.
  • the reaction is kept at 90°C for 7 hours.
  • auxiliary agent aqueous solution Add the auxiliary agent aqueous solution to the reaction flask.
  • the auxiliary agent is potassium salt.
  • the mass ratio of auxiliary agent to water in the auxiliary agent aqueous solution is 1:1.
  • the mass ratio of phenylenediamine is 1:1.3, the mass ratio of o-phenylenediamine to the water initially added to the auxiliary agent aqueous solution in the reaction flask is 1.8:3.5, and the reaction is kept at 120°C for 6 hours.
  • the mother liquor is added and filtered with suction. It is rinsed with water, the filter cake is dried into benzimidazolone, and the filtrate, which is the mother liquor, is concentrated and used.
  • the yield of benzimidazolone is 99.53% and the purity is 99.05%.
  • the auxiliary agent is a mixture of iron salt and copper salt
  • the mass ratio of auxiliary agent to water in the auxiliary agent aqueous solution is 1.5:13, turn on the stirring, and add o-phenylenediamine and
  • the mass ratio of urea, urea and o-phenylenediamine is 1:1.2, and the mass ratio of o-phenylenediamine to the water initially added to the auxiliary aqueous solution in the reaction flask is 1.3:2.
  • the reaction is kept at 140°C for 4 hours.
  • auxiliary agent aqueous solution Add the auxiliary agent aqueous solution to the reaction flask.
  • the auxiliary agent is calcium salt.
  • the mass ratio of auxiliary agent to water in the auxiliary agent aqueous solution is 1.7:10.
  • the mass ratio of phenylenediamine is 1:1.3, the mass ratio of o-phenylenediamine to the water initially added to the auxiliary agent aqueous solution in the reaction flask is 1:1, and the reaction is kept at 110°C for 8 hours.
  • the mother liquor is added and filtered with suction. It is rinsed with water, the filter cake is dried into benzimidazolone, and the filtrate is the mother liquor after being concentrated.
  • the yield of benzimidazolone is 99.18% and the purity is 99.45%.
  • the present invention is not limited to the above-mentioned embodiments.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Est divulgué par la présente invention un procédé de préparation de benzimidazolone dans un solvant aqueux, le procédé consistant : à ajouter une solution aqueuse d'un additif dans un flacon à réaction, à débuter l'agitation, à ajouter de l'o-phénylènediamine et de l'urée lorsque la température monte à 90-140 °C, à maintenir la chaleur et à mettre en réaction pendant 3 à 8 heures, à ajouter la solution aqueuse de l'additif ou d'une liqueur mère une fois la réaction terminée, à réaliser une filtration par aspiration, à réaliser une lixiviation avec de l'eau pour obtenir un matériau solide qui est la benzimidazolone, à recycler la liqueur mère, à concentrer la solution de lixiviation, puis à la recycler. Une solution technique destinée à synthétiser la benzimidazolone en utilisant de l'eau comme solvant sous pression normale est obtenue, le rendement de benzimidazolone étant supérieur à 99 % et sa pureté étant supérieure à 99 %. Le présent processus utilise de l'eau comme solvant, permet le recyclage de la liqueur mère, est respectueux de l'environnement, est sûr et faisable, comporte des coûts de production, et est approprié pour une production industrielle.
PCT/CN2020/123236 2020-04-28 2020-10-23 Procédé de préparation de benzimidazolone dans un solvant aqueux WO2021218073A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010348819.2 2020-04-28
CN202010348819.2A CN111362879A (zh) 2020-04-28 2020-04-28 一种水溶剂中制备苯并咪唑酮的方法

Publications (1)

Publication Number Publication Date
WO2021218073A1 true WO2021218073A1 (fr) 2021-11-04

Family

ID=71203589

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/123236 WO2021218073A1 (fr) 2020-04-28 2020-10-23 Procédé de préparation de benzimidazolone dans un solvant aqueux

Country Status (2)

Country Link
CN (1) CN111362879A (fr)
WO (1) WO2021218073A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111362879A (zh) * 2020-04-28 2020-07-03 山东汇海医药化工有限公司 一种水溶剂中制备苯并咪唑酮的方法
CN116003298A (zh) * 2022-12-23 2023-04-25 山东汇海医药化工有限公司 一种苯并咪唑酮合成反应母液中回收尿素的方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101307023A (zh) * 2008-05-23 2008-11-19 东营市天正化工有限公司 5-乙酰乙酰氨基苯并咪唑酮的生产工艺
CN107935937A (zh) * 2017-12-14 2018-04-20 山东汇海医药化工有限公司 一种制备苯并咪唑酮的方法
CN111362879A (zh) * 2020-04-28 2020-07-03 山东汇海医药化工有限公司 一种水溶剂中制备苯并咪唑酮的方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102285924A (zh) * 2011-05-26 2011-12-21 山东汇海医药化工有限公司 一种苯并咪唑酮的合成方法
CN108558888A (zh) * 2018-05-31 2018-09-21 兰州大学 一种吩嗪并咪唑酮的合成方法
CN109627219A (zh) * 2018-12-29 2019-04-16 高邮市华宝颜料有限公司 一种5-氨基-6-甲基苯并咪唑酮的生产方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101307023A (zh) * 2008-05-23 2008-11-19 东营市天正化工有限公司 5-乙酰乙酰氨基苯并咪唑酮的生产工艺
CN107935937A (zh) * 2017-12-14 2018-04-20 山东汇海医药化工有限公司 一种制备苯并咪唑酮的方法
CN111362879A (zh) * 2020-04-28 2020-07-03 山东汇海医药化工有限公司 一种水溶剂中制备苯并咪唑酮的方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ABBAS MUHAMMAD AZHAR, HAMEED SHAHID, KRESSLER JOERG: "Preparation of 2(3H)-Benzimidazolone and its Derivative Under Aqueous Condition As a Potential Agent for Antidiabetic Compounds", ASIAN JOURNAL OF CHEMISTRY, CHEMIC PUBLISHING, SAHIBADAD, IN, vol. 25, no. 1, 1 January 2013 (2013-01-01), IN , pages 509 - 511, XP055861037, ISSN: 0970-7077, DOI: 10.14233/ajchem.2013.13372 *
JAWAD KADHIM ABDULLAH: "Synthesis and Characterization Benzimidazole Ring by using O-Phenylinediamine with Different Compounds and using Mannich Reaction to Preparation some of Derivatives", ORIENTAL JOURNAL OF CHEMISTRY, ORIENTAL SCIENTIFIC PUBLISHING COMPANY, INC., IN, vol. 34, no. 1, 28 February 2018 (2018-02-28), IN , pages 473 - 481, XP055861034, ISSN: 0970-020X, DOI: 10.13005/ojc/340152 *
TAN CHUANJIANG: "Synthesis and Improvement on Process of 5-Aminobenzimidazolone-2", CHINESE MASTER'S THESES FULL-TEXT DATABASE, TIANJIN POLYTECHNIC UNIVERSITY, CN, no. 4, 30 April 2009 (2009-04-30), CN , XP055861033, ISSN: 1674-0246 *

Also Published As

Publication number Publication date
CN111362879A (zh) 2020-07-03

Similar Documents

Publication Publication Date Title
WO2021218073A1 (fr) Procédé de préparation de benzimidazolone dans un solvant aqueux
CN107602661B (zh) 一种聚普瑞锌的制备方法
WO2021114893A1 (fr) Procédé de préparation de 5-acétyl acétylaminobenzimidazolone
CN104130194B (zh) 一种5-氨基苯并咪唑酮的合成方法
CN112717911B (zh) 一种用于制备富马酸的固体催化剂及其制备方法和应用
CN111072492A (zh) 一种合成3,4-二氯-2-氨基-5-氟联苯的方法
WO2022082723A1 (fr) Procédé pour la synthèse de n,n'-diisopropylcarbodiimide à l'aide d'oxygène en tant qu'agent oxydant
CN103803622B (zh) 一种由六水氯化铝脱水制备无水氯化铝的方法
CN105153041B (zh) 一种适用于工业化生产的5‑氟胞嘧啶的制备方法
CN108298563A (zh) 一种单氰胺水溶液的清洁制备方法
CN106905161A (zh) 一种2‑氯‑4‑氟‑5‑硝基苯甲酸的合成方法
CN103113254A (zh) 从硝基苯直接合成对乙酰氨基苯酚的工艺
CN108558790B (zh) 一种2-氨基-4-甲基苯并噻唑的制备方法
CN109734645B (zh) 一种靛红的合成工艺
CN114920670B (zh) 一种5-氯-2-氨基苯磺酰胺的制备方法
CN107739315A (zh) 间氨基乙酰苯胺盐酸盐母液的处理方法
CN117447405A (zh) 一种节能、环保制备苯并咪唑酮的方法
CN114773177B (zh) 一种以乌尔丝d为原料制备氯冉的方法
CN105524005B (zh) 一种从三聚氰酸废渣中回收三聚氰酸的方法
WO2024125580A1 (fr) Procédé de préparation d'un intermédiaire d'oseltamivir
WO2022088302A1 (fr) Procédé de préparation d'isophtalamide
GB2077261A (en) Process for the manufacture of 2-6 dichloro-4-nitroaniline
CN100500572C (zh) 氟化亚铜晶体的水热还原法制备方法
CN115772099A (zh) 一种dcc生产中异硫氰酸环己酯杂质的处理方法
CN105732510A (zh) 5，6-二氨基苯并咪唑酮-2的制备方法

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: 20933602

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20933602

Country of ref document: EP

Kind code of ref document: A1