WO2017100985A1 - Procédé de préparation de dérivés 2,2-dihalo-1,3-dicarbonyle - Google Patents

Procédé de préparation de dérivés 2,2-dihalo-1,3-dicarbonyle Download PDF

Info

Publication number
WO2017100985A1
WO2017100985A1 PCT/CN2015/097321 CN2015097321W WO2017100985A1 WO 2017100985 A1 WO2017100985 A1 WO 2017100985A1 CN 2015097321 W CN2015097321 W CN 2015097321W WO 2017100985 A1 WO2017100985 A1 WO 2017100985A1
Authority
WO
WIPO (PCT)
Prior art keywords
propanedione
phenyl
ethyl acetate
reaction
dicarbonyl derivative
Prior art date
Application number
PCT/CN2015/097321
Other languages
English (en)
Chinese (zh)
Inventor
邹建平
周少方
张国玉
张令
Original Assignee
苏州大学张家港工业技术研究院
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 苏州大学张家港工业技术研究院 filed Critical 苏州大学张家港工业技术研究院
Priority to PCT/CN2015/097321 priority Critical patent/WO2017100985A1/fr
Publication of WO2017100985A1 publication Critical patent/WO2017100985A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B39/00—Halogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/04—Saturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/16—Saturated compounds containing keto groups bound to acyclic carbon atoms containing halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/80—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen
    • C07C49/813—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen polycyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
    • 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
    • C07C67/307—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 halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/62—Halogen-containing esters
    • C07C69/63—Halogen-containing esters of saturated acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
    • C07C69/716—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids

Definitions

  • the present invention relates to the technical field of preparation of organic compounds, and in particular to a method for preparing a 2,2-dihalo-1,3-dicarbonyl derivative.
  • 2,2-Dichloro-1,3-dicarbonyl derivatives are an important class of pharmaceutical and pesticide intermediates.
  • Sun has published a process for the preparation of 2-chloro-1,3-benzenediol from 2,2-dichloro-1,3-cyclohexanedione.
  • 2-Chloro-1,3-benzenediol is an important pharmaceutical and dye intermediate widely used in the synthesis of pharmaceuticals, pesticides and dyes. Its technical route is as follows:
  • 1,3-cycloheptanedione can be prepared from 2,2-dichlorocycloheptane-1,3-dione, which is an important pharmaceutical intermediate.
  • Tippe discloses a kind of 2,2-dichloro-4-(2,4-dichlorophenoxy)-1-phenyl-1,3-butanedione (1)
  • the 2,2-dichloro-1,3-dicarbonyl compound is prepared by using the KCIO 3 /NaHSO 3 /ZnSO 4 system, which has the disadvantages of narrow application range, high risk of operation, and large material loss.
  • a method for preparing a 2,2-dichloro-1,3-dicarbonyl derivative using PhICl 2 as a chlorinating reagent which has a disadvantage that the substrate is difficult to obtain, the operation process is dangerous, and the chlorinating reagent is expensive.
  • the synthetic methods for the disclosed 2,2-dibromo-1,3-dicarbonyl derivatives are mainly as follows:
  • a 2,2-dibromo-1,3-dicarbonyl derivative was prepared by a grinding method, and the method disclosed the results of three 2,2-dibromo-1,3-dicarbonyl derivatives, Insufficient application range, difficulty in amplification, etc.; Preparation of 2,2-dibromo-1,3-dicarbonyl derivative by using 0 XOne /NH 4 Br, the method is only applicable to 5 2,2-dibromo- The 1,3-dicarbonyl derivative has the disadvantages of a narrow application range of the substrate, a high risk of operation, and difficulty in amplification.
  • the dihalogenation technology of the disclosed 1,3-dicarbonyl derivatives has difficulty in obtaining substrates, narrow application range of substrates, harsh reaction conditions, expensive halogenated reagents, high production cost, high pollution, and inconvenient operation.
  • the scale of the reaction is difficult to enlarge. Therefore, it is important to find a method that meets the requirements of green chemistry, has mild reaction conditions, is universally suitable, and is suitable for large-scale production.
  • An object of the present invention is to provide a process for preparing a 2,2-dihalo-1,3-dicarbonyl derivative which has a simple source of raw materials, high yield, mild reaction conditions and good universality. advantage.
  • the technical solution adopted by the present invention is: a dihalogenation method of a 1,3-dicarbonyl derivative, comprising the steps of: 1,3-dicarbonyl derivative, sodium sulphate The manganese acetate and the copper catalyst are added to the solvent and reacted at 30 to 90 ° C to obtain a 2,2-di-1,3-dicarbonyl derivative;
  • the 1,3-dicarbonyl derivative is represented by the following chemical structural formula:
  • R 2 is selected from the group consisting of: an alkyl group, an aryl group, a heteroaryl group or an alkoxy group; and R 2 is selected from the group consisting of: an alkyl group, an aryl group
  • the sodium salt is sodium bromide or sodium chloride
  • the copper catalyst has the chemical formula CuX n , wherein X is C1 or Br;
  • the solvent is selected from the group consisting of: methanol, ethanol, ethylene glycol, acetonitrile, acetic acid, propionic acid, dimethylformamide One.
  • the 2,2-di-1,3-dicarbonyl derivative is represented by the following chemical structural formula:
  • the 1,3-dicarbonyl derivative is selected from the group consisting of ethyl benzoate, ethyl (4-methylbenzoyl)acetate, and (4-methoxybenzoyl) Ethyl acetate, (2-methylbenzoyl) ethyl acetate, (
  • the present invention uses sodium bromide or sodium chloride as a raw material, and reacts with a 1,3-dicarbonyl derivative to prepare a product; sodium hydride is used, in a molar ratio, 1,3-dicarbonyl derivative: sodium halide : Manganese acetate:
  • the copper catalyst is 1:2: (2 to 8): (0.08-0.12);
  • the 1,3-dicarbonyl derivative: manganese acetate: the copper catalyst is 1:4:0.1.
  • 1,3-dicarbonyl derivative sodium halide: manganese acetate: copper catalyst is 1:2: (6 ⁇ 8): (0.08-0.12); preferably, 1, 3-Dicarbonyl derivative: Manganese acetate: The copper catalyst was 1:7:0.1.
  • the product is subjected to column chromatography separation and purification after the reaction is completed; column chromatography separation Purification treatment with petroleum ether / ethyl acetate as the eluent, preferably the volume ratio of petroleum ether to ethyl acetate is 20:
  • the preferred reaction temperature of the present invention is from 60 to 70 °C.
  • the reaction is mild, the product yield is high, and energy waste is avoided.
  • the reaction process of the above technical solution can be expressed as:
  • the present invention uses the 1,3-dicarbonyl derivative and the sodium halide as the starting materials for the first time, and efficiently prepares 2,2-dihalo-1 in air in the presence of manganese acetate and a copper catalyst.
  • 3-dicarbonyl derivative easy to obtain raw materials, many kinds of products, the prepared product can be used directly, can also be used as an intermediate for other further reactions
  • the invention has simple raw materials, does not need various compounding reagents required by the prior art, has small reagent dosage, good selectivity, low cost, and avoids the application of existing toxic compounds and reduces pollution environment; A small amount of catalyst can efficiently obtain the product, which not only simplifies the purification process of the product, but also reduces the generation of waste. Moreover, manganese acetate and copper catalyst can be recycled, avoiding waste of raw materials, and has positive practical significance for industrial applications.
  • the preparation method of the present invention has simple reaction conditions, does not require a complicated atmosphere environment of the prior art, and can efficiently obtain a product by reacting in air, and the post-treatment is very simple, and column chromatography can be performed, thereby avoiding the existing reaction.
  • the risk factors in the process are conducive to chemical synthesis and safe production, and to ensure the safety of life and property.
  • the reaction is carried out in air, the reaction conditions are mild, the pollution is small, and the reaction time is short, and is particularly suitable for various 1,3-dicarbonyl derivatives, and the yield of the target product. High, easy to handle and post-process, suitable for industrial production.
  • the catalyst bromide in the reaction of the present invention and the manganese acetate which is not consumed in the reaction can be further utilized by the second reaction, and the subsequent reaction does not require the addition of the catalyst copper bromide, as long as the appropriate amount of manganese acetate is added, plus Other reactants and solvents can be used, so that resources can be reused to save resources and reduce pollution.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé de préparation de dérivés 2,2-dihalo-1,3-dicarbonyle. Ledit procédé peut être appliqué à une large gamme de dérivés 1,3-dicarbonyle, qui présentent divers types de matières premières facilement disponibles. Ledit procédé est utilisé pour produire divers types de produits, qui peuvent non seulement être utilisés directement, mais peuvent également être utilisés pour d'autres réactions. Ledit procédé présente des conditions de réaction douces, comprend des opérations et un processus de post-traitement simples, un temps de réaction court, un rendement élevé, et une pollution réduite et est approprié pour une production à l'échelle industrielle.
PCT/CN2015/097321 2015-12-14 2015-12-14 Procédé de préparation de dérivés 2,2-dihalo-1,3-dicarbonyle WO2017100985A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2015/097321 WO2017100985A1 (fr) 2015-12-14 2015-12-14 Procédé de préparation de dérivés 2,2-dihalo-1,3-dicarbonyle

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2015/097321 WO2017100985A1 (fr) 2015-12-14 2015-12-14 Procédé de préparation de dérivés 2,2-dihalo-1,3-dicarbonyle

Publications (1)

Publication Number Publication Date
WO2017100985A1 true WO2017100985A1 (fr) 2017-06-22

Family

ID=59055619

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2015/097321 WO2017100985A1 (fr) 2015-12-14 2015-12-14 Procédé de préparation de dérivés 2,2-dihalo-1,3-dicarbonyle

Country Status (1)

Country Link
WO (1) WO2017100985A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109384671A (zh) * 2017-08-09 2019-02-26 上海沃凯生物技术有限公司 一种溴代丙二酸二酯的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0687665A1 (fr) * 1994-06-10 1995-12-20 Hüls Aktiengesellschaft Procédé pour la préparation des esters de l'acide malonique 2,2 dichloré
CN105523874A (zh) * 2015-12-14 2016-04-27 苏州大学张家港工业技术研究院 一种2,2-二卤代-1,3-二羰基衍生物的制备方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0687665A1 (fr) * 1994-06-10 1995-12-20 Hüls Aktiengesellschaft Procédé pour la préparation des esters de l'acide malonique 2,2 dichloré
CN105523874A (zh) * 2015-12-14 2016-04-27 苏州大学张家港工业技术研究院 一种2,2-二卤代-1,3-二羰基衍生物的制备方法

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DI, JUCAI ET AL.: "A New Method for the Halogenation of 1,3-Dicarbonyl Compounds", NATURAL SCIENCE EDITION, vol. 24, no. 3, 10 July 2008 (2008-07-10), pages 75 - 78, ISSN: 1000-2073 *
KIM, J.J. ET AL.: "Conversion of Nucleophilic Halides to Electrophilic Halides: Efficient and Selective Halogenation of Azinones, Amides, and Carbonyl Compounds Using Metal Halide/Lead Tetraacetate", SYNLETT, 24 January 2006 (2006-01-24), pages 194 - 200, ISSN: 0936-5214 *
MACHARLA, A.K. ET AL.: "Oxidative Bromination of Ketones Using Ammonium Bromide and Oxone", TETRAHEDRON LETTERS, vol. 53, no. 2, 9 November 2011 (2011-11-09), pages 191 - 195, XP028393251, ISSN: 0040-4039 *
SHI, X.X. ET AL.: "Mild Halogenation of Stabilized Ester Enolates by Cupric Halides", J. ORG. CHEM., vol. 58, no. 17, 1 August 1993 (1993-08-01), pages 4596 - 4598, XP055392579, ISSN: 0022-3263 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109384671A (zh) * 2017-08-09 2019-02-26 上海沃凯生物技术有限公司 一种溴代丙二酸二酯的制备方法

Similar Documents

Publication Publication Date Title
Khazaei et al. Trityl chloride as an efficient organic catalyst for the synthesis of 1-amidoalkyl-2-naphtols in neutral media at room temperature
Lange et al. Decarboxylative biaryl synthesis in a continuous flow reactor
Reddy et al. Reductive amination of carbonyl compounds using NaBH4 in a Brønsted acidic ionic liquid
Rafiee et al. Cs2. 5H0. 5PW12O40 catalyzed diastereoselective synthesis of β-amino ketones via three component Mannich-type reaction in water
CA2715668A1 (fr) Procede de preparation de 2-alcoxymethylene-4,4-difluoro-3-oxobutyrates d'alkyle
Muñoz et al. Application of flow chemistry to the reduction of nitriles to aldehydes
CN102249879A (zh) 一种1, 2-二酮衍生物及其制备方法
Zarei et al. Aryldiazonium silica sulfates as efficient reagents for Heck-type arylation reactions under mild conditions
CN103664602A (zh) 一种α, β-不饱和羧酸酯类化合物及其制备方法
CN109232212B (zh) 一种由异戊烯醇合成甲基庚烯酮的方法
WO2017100985A1 (fr) Procédé de préparation de dérivés 2,2-dihalo-1,3-dicarbonyle
CN104086488B (zh) 一种2,4,6-三取代嘧啶类化合物的合成方法
CN103333123B (zh) 一种二氢喹唑啉酮化合物的脱卤方法
CN102702175B (zh) 一种吲哚-3-琥珀酰亚胺的制备方法
CN105367399A (zh) 一种9,10-菲醌类化合物的制备方法
US8609886B2 (en) Method for producing high purity terminal olefin compound
Chen et al. Copper-catalyzed aerobic oxidative cross-coupling reactions of vinylarenes with sulfinate salts: A direct approach to β-ketosulfones
EP3196183B1 (fr) Procédé de production d'une cétone aromatique substituée par un groupe 2'-trifluorométhyle
CN109232316B (zh) 一类α-三级腈结构β-二羰基化合物的合成方法
CN108358866B (zh) 一种非布司他中间体的制备方法及其在制备非布司他中的应用
CN104262123A (zh) 一种2-环己烯酮及其衍生物的合成方法
EP3224229B1 (fr) Procédé de production du 7,8-dihydro-c15-aldéhyde
CN104262085A (zh) 一种4-卤代苯乙炔的合成新方法
CN102382056B (zh) 5-羟基-取代吡唑的制备方法
CN110156716B (zh) 一种苯并噻唑酯类衍生物的合成方法

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: 15910458

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: 15910458

Country of ref document: EP

Kind code of ref document: A1