CN115772105B - Synthesis method of 4-nitroanisole - Google Patents
Synthesis method of 4-nitroanisole Download PDFInfo
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- BNUHAJGCKIQFGE-UHFFFAOYSA-N Nitroanisol Chemical compound COC1=CC=C([N+]([O-])=O)C=C1 BNUHAJGCKIQFGE-UHFFFAOYSA-N 0.000 title claims description 17
- 238000001308 synthesis method Methods 0.000 title 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 70
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims abstract description 42
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 28
- CZGCEKJOLUNIFY-UHFFFAOYSA-N 4-Chloronitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1 CZGCEKJOLUNIFY-UHFFFAOYSA-N 0.000 claims abstract description 24
- 235000003270 potassium fluoride Nutrition 0.000 claims abstract description 21
- 239000011698 potassium fluoride Substances 0.000 claims abstract description 21
- 239000002994 raw material Substances 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 120
- 238000000605 extraction Methods 0.000 claims description 13
- 239000012074 organic phase Substances 0.000 claims description 9
- 238000000746 purification Methods 0.000 claims description 9
- 238000001953 recrystallisation Methods 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical group [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 claims description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 4
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 claims description 3
- -1 4-nitroanisole sulfide Chemical compound 0.000 claims description 3
- 239000000047 product Substances 0.000 claims 6
- 239000012295 chemical reaction liquid Substances 0.000 claims 2
- 238000010189 synthetic method Methods 0.000 claims 2
- 239000012043 crude product Substances 0.000 claims 1
- 238000010025 steaming Methods 0.000 claims 1
- NEZGPRYOJVPJKL-UHFFFAOYSA-N 1-methylsulfanyl-4-nitrobenzene Chemical compound CSC1=CC=C([N+]([O-])=O)C=C1 NEZGPRYOJVPJKL-UHFFFAOYSA-N 0.000 abstract description 42
- 238000009776 industrial production Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 description 9
- 238000004821 distillation Methods 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000000376 reactant Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 4
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 3
- SCCCFNJTCDSLCY-UHFFFAOYSA-N 1-iodo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(I)C=C1 SCCCFNJTCDSLCY-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- FYFDQJRXFWGIBS-UHFFFAOYSA-N 1,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C([N+]([O-])=O)C=C1 FYFDQJRXFWGIBS-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- KFIMOMYDCZFXKC-UHFFFAOYSA-N (4-methylphenyl)-oxido-sulfanylideneazanium Chemical compound CC1=CC=C([N+]([O-])=S)C=C1 KFIMOMYDCZFXKC-UHFFFAOYSA-N 0.000 description 1
- XONGBDXIFQIQBN-UHFFFAOYSA-N 1-methylsulfonyl-4-nitrobenzene Chemical compound CS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 XONGBDXIFQIQBN-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- YKFROQCFVXOUPW-UHFFFAOYSA-N 4-(methylthio) aniline Chemical compound CSC1=CC=C(N)C=C1 YKFROQCFVXOUPW-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 101001121408 Homo sapiens L-amino-acid oxidase Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102100026388 L-amino-acid oxidase Human genes 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供一种4‑硝基茴香硫醚的合成方法。以对硝基氯苯、氟化钾以及二甲基亚砜为原料,在催化剂的作用下,反应生成4‑硝基茴香硫醚。本发明涉及的4‑硝基茴香硫醚合成工艺所有原料,来源广泛且价格低廉,反应条件温和、工艺相对简单,各步反应均为常规操作,且产物收率较高。该方法满足工业化生产4‑硝基茴香硫醚的基本要求。The present invention provides a method for synthesizing 4-nitrothioanisole. Using p-nitrochlorobenzene, potassium fluoride and dimethyl sulfoxide as raw materials, under the action of a catalyst, 4-nitrothioanisole is reacted. All raw materials of the 4-nitrothioanisole synthesis process of the present invention are widely available and inexpensive, the reaction conditions are mild, the process is relatively simple, each step of the reaction is a conventional operation, and the product yield is high. The method meets the basic requirements for the industrial production of 4-nitrothioanisole.
Description
技术领域Technical Field
本发明属于精细化工技术领域,具体涉及一种以对硝基氯苯和氟化钾为原料在二甲基亚砜中反应合成4-硝基茴香硫醚的方法。The invention belongs to the technical field of fine chemicals, and particularly relates to a method for synthesizing 4-nitrothioanisole by reacting p-nitrochlorobenzene and potassium fluoride as raw materials in dimethyl sulfoxide.
背景技术Background technique
4-硝基茴香硫醚,又称对甲硫基硝基苯、对硝基甲苯硫醚,常温下为浅黄色至棕黄色固体,易溶于乙酸乙酯等有机溶剂,其结构式如式S-1所示。4-硝基茴香硫醚用途广泛,是医药、农药、兽药等精细化工常用的中间体。如4-硝基茴香硫醚经过加氢还原制得4-氨基茴香硫醚,该中间体是非甾体药物艾沙利酮(专利CN 114456098)的重要原料之一。4-Nitrothioanisole, also known as p-methylthionitrobenzene and p-nitrotoluene thioether, is a light yellow to brown solid at room temperature and is easily soluble in organic solvents such as ethyl acetate. Its structural formula is shown in Formula S-1. 4-Nitrothioanisole has a wide range of uses and is a commonly used intermediate in fine chemicals such as medicine, pesticides, and veterinary drugs. For example, 4-nitrothioanisole is hydrogenated to produce 4-aminothioanisole, which is one of the important raw materials for the non-steroidal drug esalidonate (patent CN 114456098).
文献(Journal of Fluorine Chemistry,245,109778;2021)报道以对硝基氟苯与二甲基二硫醚反应制备4-硝基茴香硫醚;文献(Tetrahedron Letters,56(37),5199-5202;2015)报道以对硝基碘苯或对硝基溴苯在碘化亚铜/三乙烯二胺催化下与二甲亚砜反应制备4-硝基茴香硫醚;文献(Tetrahedron Letters,56(38),5323-5326;2014)报道以对硝基氟苯或对硝基氯苯或对二硝基苯在在N,N-二异丙基乙胺催化下与二甲亚砜反应制备4-硝基茴香硫醚,其中以对硝基氯苯为底物进行反应目标产物收率仅为49%。在该合成路线中,所用原料硝基苯衍生物(对氟硝基苯、对溴硝基苯、对碘硝基苯及对二硝基苯)及催化剂价格较贵、成本较高,或产物收率很低(如以对氯硝基苯为底物)。文献(Phosphorus,Sulfurand Silicon and the Related Elements,190(7),1169-1176;2015)使用1-甲磺亚酰基4-硝基苯合成4-硝基茴香硫醚,所用原料昂贵,不适合工业生产。文献还报道了其他以对硝基碘苯或对硝基溴苯或对硝基氯苯与二甲基亚砜反应制备4-硝基茴香硫醚的方法。在该类合成路线中,对硝基碘苯或对硝基溴苯价格较贵、成本较高,不适用于工业生产;以对硝基氯苯为原料时产率较低且反应时间较长,同样不利于其工业生产。The literature (Journal of Fluorine Chemistry, 245, 109778; 2021) reported that 4-nitroanisole was prepared by the reaction of p-nitrofluorobenzene with dimethyl disulfide; the literature (Tetrahedron Letters, 56(37), 5199-5202; 2015) reported that 4-nitroanisole was prepared by the reaction of p-nitroiodobenzene or p-nitrobromobenzene with dimethyl sulfoxide under the catalysis of cuprous iodide/triethylenediamine; the literature (Tetrahedron Letters, 56(38), 5323-5326; 2014) reported that 4-nitroanisole was prepared by the reaction of p-nitrofluorobenzene or p-nitrochlorobenzene or p-dinitrobenzene with dimethyl sulfoxide under the catalysis of N,N-diisopropylethylamine, wherein the yield of the target product in the reaction with p-nitrochlorobenzene as the substrate was only 49%. In this synthetic route, the raw materials nitrobenzene derivatives (p-fluoronitrobenzene, p-bromonitrobenzene, p-iodinitrobenzene and p-dinitrobenzene) and catalysts used are expensive, the cost is high, or the product yield is very low (such as using p-chloronitrobenzene as a substrate). The literature (Phosphorus, Sulfur and Silicon and the Related Elements, 190 (7), 1169-1176; 2015) uses 1-methylsulfonyl 4-nitrobenzene to synthesize 4-nitrothioanisole, and the raw materials used are expensive and not suitable for industrial production. The literature also reports other methods for preparing 4-nitrothioanisole by reacting p-nitroiodobenzene, p-nitrobromobenzene or p-nitrochlorobenzene with dimethyl sulfoxide. In this type of synthetic route, p-nitroiodobenzene or p-nitrobromobenzene is expensive and the cost is high, so it is not suitable for industrial production; when p-nitrochlorobenzene is used as a raw material, the yield is low and the reaction time is long, which is also not conducive to its industrial production.
综上所述,目前4-硝基茴香硫醚的合成方案均存在一定缺陷和不足,因此开发一个收率高、成本低、工艺简单的合成工艺对4-硝基茴香硫醚的工业化生产意义重大。In summary, the current synthesis schemes of 4-nitrothioanisole all have certain defects and shortcomings. Therefore, developing a synthesis process with high yield, low cost and simple process is of great significance for the industrial production of 4-nitrothioanisole.
发明内容Summary of the invention
本发明要解决的技术问题是提供一种新的4-硝基茴香硫醚的合成方法,The technical problem to be solved by the present invention is to provide a new method for synthesizing 4-nitrothioanisole.
本发明的技术方案是:The technical solution of the present invention is:
一种4-硝基茴香硫醚的合成方法,包括如下步骤:以对硝基氯苯、氟化钾以及二甲基亚砜为原料,在催化剂的作用下,反应生成4-硝基茴香硫醚。A method for synthesizing 4-nitrothioanisole comprises the following steps: using p-nitrochlorobenzene, potassium fluoride and dimethyl sulfoxide as raw materials, reacting in the presence of a catalyst to generate 4-nitrothioanisole.
优选地,按质量比,硝基氯苯、氟化钾以及二甲基亚砜的比例为氟化钾10-15份:对硝基氯苯10-20份:二甲基亚砜30-100份。Preferably, in terms of mass ratio, the ratio of nitrochlorobenzene, potassium fluoride and dimethyl sulfoxide is 10-15 parts of potassium fluoride: 10-20 parts of p-nitrochlorobenzene: 30-100 parts of dimethyl sulfoxide.
优选地,反应温度为185-220℃,反应时间为12~15h。Preferably, the reaction temperature is 185-220° C., and the reaction time is 12 to 15 hours.
优选地,所述的催化剂为四甲基氯化铵或聚乙二醇2000。Preferably, the catalyst is tetramethylammonium chloride or polyethylene glycol 2000.
优选地,催化剂使用量为1-30份。Preferably, the catalyst is used in an amount of 1-30 parts.
本发明的另一技术方案为:Another technical solution of the present invention is:
一种4-硝基茴香硫醚的合成方法,包括如下步骤:A method for synthesizing 4-nitrothioanisole comprises the following steps:
将氟化钾10-15份,对硝基氯苯10-20份,催化剂1-30份,二甲基亚砜30-100份加入到反应器中反应,反应温度为185-220℃,反应时间为12~15h生成目标产物4-硝基茴香硫醚。10-15 parts of potassium fluoride, 10-20 parts of p-nitrochlorobenzene, 1-30 parts of catalyst and 30-100 parts of dimethyl sulfoxide are added into a reactor for reaction at a temperature of 185-220° C. for 12-15 hours to generate the target product 4-nitrothioanisole.
优选地,生成目标产物4-硝基茴香硫醚之后,还包括产品提取步骤和提纯步骤。Preferably, after the target product 4-nitrothioanisole is generated, the process further includes a product extraction step and a purification step.
优选地,所述的产品提取步骤包括:Preferably, the product extraction step comprises:
反应结束后减压蒸除反应液中剩余的二甲基亚砜,然后向其中加入适量水和乙酸乙酯进行洗涤和萃取,脱除所得有机相中的乙酸乙酯即得4-硝基茴香硫醚粗产品;After the reaction is completed, the remaining dimethyl sulfoxide in the reaction solution is evaporated under reduced pressure, and then appropriate amounts of water and ethyl acetate are added thereto for washing and extraction, and the ethyl acetate in the obtained organic phase is removed to obtain a crude 4-nitrothioanisole product;
优选地,提纯步骤是将所得4-硝基茴香硫醚粗产品提纯,得产品4-硝基茴香硫醚。Preferably, the purification step is to purify the obtained crude 4-nitrothioanisole product to obtain the product 4-nitrothioanisole.
优选地,所述提纯的方法采用重结晶或精馏。Preferably, the purification method is recrystallization or distillation.
在本发明中,在二甲基亚砜溶剂中,在催化剂催化下,对硝基氯苯、氟化钾发生反应生成含氟中间体(所得中间体无需分离),所得中间体与二甲基亚砜进一步发生反应得到目标产物4-硝基茴香硫醚。反应方程式如S-2所示。In the present invention, in a dimethyl sulfoxide solvent, under the catalysis of a catalyst, p-nitrochlorobenzene and potassium fluoride react to generate a fluorine-containing intermediate (the intermediate does not need to be separated), and the intermediate further reacts with dimethyl sulfoxide to obtain the target product 4-nitrothioanisole. The reaction equation is shown in S-2.
本发明的合成产物可由NMR进行分析。The synthetic product of the present invention can be analyzed by NMR.
本发明与现有技术相比,其有益效果为:Compared with the prior art, the present invention has the following beneficial effects:
采用本发明的方法制备4-硝基茴香硫醚,以对硝基氯苯及氟化钾为主原料、二甲基亚砜作为硫甲基化试剂及溶剂,可以在较温和的反应条件下以较高的收率获得4-硝基茴香硫醚。该工艺原料成本低廉、反应及后处理工艺简单,在较优工艺条件下目标产物收率接近90%。与现有技术相比,本发明具有原料成本低、操作方便、收率高、后处理工艺简单等优点,是一种高效、低成本制备4-硝基茴香硫醚硫醚的方法。The method of the present invention is used to prepare 4-nitrothioanisole. With p-nitrochlorobenzene and potassium fluoride as main raw materials and dimethyl sulfoxide as a thiomethylation reagent and solvent, 4-nitrothioanisole can be obtained with a high yield under mild reaction conditions. The process has low raw material cost, simple reaction and post-processing processes, and the yield of the target product is close to 90% under better process conditions. Compared with the prior art, the present invention has the advantages of low raw material cost, convenient operation, high yield, simple post-processing process, etc., and is an efficient and low-cost method for preparing 4-nitrothioanisole sulfide.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
下面结合附图对本发明的具体实施方案进一步详细说明The specific embodiments of the present invention are further described in detail below with reference to the accompanying drawings.
图1是本发明实施例3的4-硝基茴香硫醚的核磁氢谱图。FIG1 is a hydrogen nuclear magnetic spectrum of 4-nitrothioanisole of Example 3 of the present invention.
图2是本发明实施例3的4-硝基茴香硫醚的核磁碳谱图。FIG. 2 is a carbon NMR spectrum of 4-nitrothioanisole of Example 3 of the present invention.
具体实施方式Detailed ways
本发明一种4-硝基茴香硫醚的合成方法,包括如下步骤:以对硝基氯苯、氟化钾以及二甲基亚砜为原料,在催化剂的作用下,反应生成4-硝基茴香硫醚。The invention discloses a method for synthesizing 4-nitrothioanisole, which comprises the following steps: taking p-nitrochlorobenzene, potassium fluoride and dimethyl sulfoxide as raw materials, and reacting in the presence of a catalyst to generate 4-nitrothioanisole.
优选地,按质量比,硝基氯苯、氟化钾以及二甲基亚砜的比例为氟化钾10-15份:对硝基氯苯10-20份:二甲基亚砜30-100份。Preferably, in terms of mass ratio, the ratio of nitrochlorobenzene, potassium fluoride and dimethyl sulfoxide is 10-15 parts of potassium fluoride: 10-20 parts of p-nitrochlorobenzene: 30-100 parts of dimethyl sulfoxide.
实施例1Example 1
(1)称取1.0g氟化钾、1.2g对硝基氯苯、0.18g四甲基氯化铵、5.5g二甲基亚砜于可加热耐压反应器中,油浴加热至220℃搅拌反应15小时;(1) Weigh 1.0 g of potassium fluoride, 1.2 g of p-nitrochlorobenzene, 0.18 g of tetramethylammonium chloride, and 5.5 g of dimethyl sulfoxide in a heatable pressure-resistant reactor, heat to 220° C. in an oil bath, and stir to react for 15 hours;
(2)反应结束降温后减压蒸除反应液中剩余的二甲基亚砜,随后向其中加入50ml水和15ml乙酸乙酯进行洗涤和萃取,所得水相再使用乙酸乙酯萃取2次(每次使用乙酸乙酯15ml),脱除所得有机相中的溶剂乙酸乙酯后得到4-硝基茴香硫醚粗产品1.3g,对其进一步纯化后获得1.15g产品4-硝基茴香硫醚,收率89.2%;(2) After the reaction was completed and the temperature was lowered, the remaining dimethyl sulfoxide in the reaction solution was evaporated under reduced pressure, and then 50 ml of water and 15 ml of ethyl acetate were added thereto for washing and extraction. The obtained aqueous phase was extracted twice with ethyl acetate (15 ml of ethyl acetate was used each time), and the solvent ethyl acetate in the obtained organic phase was removed to obtain 1.3 g of crude 4-nitrothioanisole. After further purification, 1.15 g of product 4-nitrothioanisole was obtained, with a yield of 89.2%;
反应物萃取旋蒸后脱除乙酸乙酯冷却至室温为胶状混合物,可通过精馏或重结晶对其进一步纯化。The reactants are extracted and rotary evaporated to remove ethyl acetate and cooled to room temperature to obtain a colloidal mixture, which can be further purified by distillation or recrystallization.
实施例2Example 2
(1)称取1.0g氟化钾、1.2g对硝基氯苯、0.18g四甲基氯化铵、5.5g二甲基亚砜于可加热耐压反应器中,油浴加热至220℃搅拌反应12小时;(1) Weigh 1.0 g of potassium fluoride, 1.2 g of p-nitrochlorobenzene, 0.18 g of tetramethylammonium chloride, and 5.5 g of dimethyl sulfoxide in a heatable pressure-resistant reactor, heat to 220° C. in an oil bath, and stir to react for 12 hours;
(2)反应结束降温后减压蒸除反应液中剩余的二甲基亚砜,随后向其中加入50ml水和15ml乙酸乙酯进行洗涤和萃取,所得水相再使用乙酸乙酯萃取2次(每次使用乙酸乙酯15ml),脱除所得有机相中的溶剂乙酸乙酯后得到4-硝基茴香硫醚粗产品1.3g,对其进一步纯化后获得1.06g产品4-硝基茴香硫醚,收率82.2%;(2) After the reaction was completed and the temperature was lowered, the remaining dimethyl sulfoxide in the reaction solution was evaporated under reduced pressure, and then 50 ml of water and 15 ml of ethyl acetate were added thereto for washing and extraction. The obtained aqueous phase was extracted twice with ethyl acetate (15 ml of ethyl acetate was used each time), and the solvent ethyl acetate in the obtained organic phase was removed to obtain 1.3 g of crude 4-nitrothioanisole. After further purification, 1.06 g of product 4-nitrothioanisole was obtained, with a yield of 82.2%;
反应物萃取旋蒸后脱除乙酸乙酯冷却至室温为胶状混合物,可通过精馏或重结晶对其进一步纯化。The reactants are extracted and rotary evaporated to remove ethyl acetate and cooled to room temperature to obtain a colloidal mixture, which can be further purified by distillation or recrystallization.
实施例3Example 3
(1)称取0.9g氟化钾、1.2g对硝基氯苯、0.17g四甲基氯化铵、5.5g二甲基亚砜于可加热耐压反应器中,油浴加热至220℃搅拌反应12小时;(1) Weigh 0.9 g potassium fluoride, 1.2 g p-nitrochlorobenzene, 0.17 g tetramethylammonium chloride, and 5.5 g dimethyl sulfoxide in a heatable pressure-resistant reactor, heat to 220° C. in an oil bath, and stir to react for 12 hours;
(2)反应结束降温后减压蒸除反应液中剩余的二甲基亚砜,随后向其中加入50ml水和15ml乙酸乙酯进行洗涤和萃取,所得水相再使用乙酸乙酯萃取2次(每次使用乙酸乙酯15ml),脱除所得有机相中的溶剂乙酸乙酯后得到4-硝基茴香硫醚粗产品1.3g,对其进一步纯化后获得1.07g产品4-硝基茴香硫醚,收率83.0%;(2) After the reaction was completed and the temperature was lowered, the remaining dimethyl sulfoxide in the reaction solution was distilled off under reduced pressure, and then 50 ml of water and 15 ml of ethyl acetate were added thereto for washing and extraction. The obtained aqueous phase was extracted twice with ethyl acetate (15 ml of ethyl acetate was used each time), and the solvent ethyl acetate in the obtained organic phase was removed to obtain 1.3 g of crude 4-nitrothioanisole. After further purification, 1.07 g of product 4-nitrothioanisole was obtained, with a yield of 83.0%;
反应物萃取旋蒸后脱除乙酸乙酯冷却至室温为胶状混合物,可通过精馏或重结晶对其进一步纯化。The reactants are extracted and rotary evaporated to remove ethyl acetate and cooled to room temperature to obtain a colloidal mixture, which can be further purified by distillation or recrystallization.
实施例4Example 4
(1)称取1.0g氟化钾、1.2g对硝基氯苯、0.18g四甲基氯化铵、5.5g二甲基亚砜于可加热耐压反应器中,油浴加热至185℃搅拌反应12小时;(1) Weigh 1.0 g of potassium fluoride, 1.2 g of p-nitrochlorobenzene, 0.18 g of tetramethylammonium chloride, and 5.5 g of dimethyl sulfoxide in a heatable pressure-resistant reactor, heat to 185° C. in an oil bath, and stir to react for 12 hours;
(2)反应结束降温后减压蒸除反应液中剩余的二甲基亚砜,随后向其中加入50ml水和15ml乙酸乙酯进行洗涤和萃取,所得水相再使用乙酸乙酯萃取2次(每次使用乙酸乙酯15ml),脱除所得有机相中的溶剂乙酸乙酯后得到4-硝基茴香硫醚粗产品1.0g,对其进一步纯化后获得0.62g产品4-硝基茴香硫醚,收率48.0%;(2) After the reaction was completed and the temperature was lowered, the remaining dimethyl sulfoxide in the reaction solution was distilled off under reduced pressure, and then 50 ml of water and 15 ml of ethyl acetate were added thereto for washing and extraction. The obtained aqueous phase was extracted twice with ethyl acetate (15 ml of ethyl acetate was used each time), and the solvent ethyl acetate in the obtained organic phase was removed to obtain 1.0 g of crude 4-nitrothioanisole, which was further purified to obtain 0.62 g of product 4-nitrothioanisole, with a yield of 48.0%;
反应物萃取旋蒸后脱除乙酸乙酯冷却至室温为胶状混合物,可通过精馏或重结晶对其进一步纯化。The reactants are extracted and rotary evaporated to remove ethyl acetate and cooled to room temperature to obtain a colloidal mixture, which can be further purified by distillation or recrystallization.
实施例5Example 5
(1)称取1.0g氟化钾、1.2g对硝基氯苯、3.2g聚乙二醇2000、5.5g二甲基亚砜于可加热耐压反应器中,油浴加热至220℃搅拌反应15小时;(1) Weigh 1.0 g of potassium fluoride, 1.2 g of p-nitrochlorobenzene, 3.2 g of polyethylene glycol 2000, and 5.5 g of dimethyl sulfoxide in a heatable pressure-resistant reactor, heat to 220° C. in an oil bath, and stir to react for 15 hours;
(2)反应结束降温后减压蒸除反应液中剩余的二甲基亚砜,随后向其中加入50ml水和15ml乙酸乙酯进行洗涤和萃取,所得水相再使用乙酸乙酯萃取2次(每次使用乙酸乙酯15ml),脱除所得有机相中的溶剂乙酸乙酯后得到4-硝基茴香硫醚粗产品1.2g,对其进一步纯化后获得0.96g产品4-硝基茴香硫醚,收率74.5%;(2) After the reaction was completed and the temperature was lowered, the remaining dimethyl sulfoxide in the reaction solution was evaporated under reduced pressure, and then 50 ml of water and 15 ml of ethyl acetate were added thereto for washing and extraction. The obtained aqueous phase was extracted twice with ethyl acetate (15 ml of ethyl acetate was used each time), and the solvent ethyl acetate in the obtained organic phase was removed to obtain 1.2 g of crude 4-nitrothioanisole, which was further purified to obtain 0.96 g of product 4-nitrothioanisole, with a yield of 74.5%;
反应物萃取旋蒸后脱除乙酸乙酯冷却至室温为胶状混合物,可通过精馏或重结晶对其进一步纯化。The reactants are extracted and rotary evaporated to remove ethyl acetate and cooled to room temperature to obtain a colloidal mixture, which can be further purified by distillation or recrystallization.
实施例6Example 6
(1)称取1.0g氟化钾、1.2g对硝基氯苯、3.2g聚乙二醇2000、5.5g二甲基亚砜于可加热耐压反应器中,油浴加热至220℃搅拌反应12小时;(1) Weigh 1.0 g of potassium fluoride, 1.2 g of p-nitrochlorobenzene, 3.2 g of polyethylene glycol 2000, and 5.5 g of dimethyl sulfoxide in a heatable pressure-resistant reactor, heat to 220° C. in an oil bath, and stir to react for 12 hours;
(2)反应结束降温后减压蒸除反应液中剩余的二甲基亚砜,随后向其中加入50ml水和15ml乙酸乙酯进行洗涤和萃取,所得水相再使用乙酸乙酯萃取2次(每次使用乙酸乙酯15ml),脱除所得有机相中的溶剂乙酸乙酯后得到4-硝基茴香硫醚粗产品1.2g,对其进一步纯化后获得0.87g产品4-硝基茴香硫醚,收率67.5%;(2) After the reaction was completed and the temperature was lowered, the remaining dimethyl sulfoxide in the reaction solution was evaporated under reduced pressure, and then 50 ml of water and 15 ml of ethyl acetate were added thereto for washing and extraction. The obtained aqueous phase was extracted twice with ethyl acetate (15 ml of ethyl acetate was used each time), and the solvent ethyl acetate in the obtained organic phase was removed to obtain 1.2 g of crude 4-nitrothioanisole, which was further purified to obtain 0.87 g of product 4-nitrothioanisole, with a yield of 67.5%;
反应物萃取旋蒸后脱除乙酸乙酯冷却至室温为胶状混合物,可通过精馏或重结晶对其进一步纯化。The reactants are extracted and rotary evaporated to remove ethyl acetate and cooled to room temperature to obtain a colloidal mixture, which can be further purified by distillation or recrystallization.
实施例7Example 7
(1)称取0.8g氟化钾、1.2g对硝基氯苯、0.6g聚乙二醇2000、5.5g二甲基亚砜于可加热耐压反应器中,油浴加热至220℃搅拌反应12小时;(1) Weigh 0.8 g potassium fluoride, 1.2 g p-nitrochlorobenzene, 0.6 g polyethylene glycol 2000, and 5.5 g dimethyl sulfoxide in a heatable pressure-resistant reactor, heat to 220° C. in an oil bath, and stir to react for 12 hours;
(2)反应结束降温后减压蒸除反应液中剩余的二甲基亚砜,随后向其中加入50ml水和15ml乙酸乙酯进行洗涤和萃取,所得水相再使用乙酸乙酯萃取2次(每次使用乙酸乙酯15ml),脱除所得有机相中的溶剂乙酸乙酯后得到4-硝基茴香硫醚粗产品1.2g,对其进一步纯化后获得0.89g产品4-硝基茴香硫醚,收率69.0%;(2) After the reaction was completed and the temperature was lowered, the remaining dimethyl sulfoxide in the reaction solution was distilled off under reduced pressure, and then 50 ml of water and 15 ml of ethyl acetate were added thereto for washing and extraction. The obtained aqueous phase was extracted twice with ethyl acetate (15 ml of ethyl acetate was used each time), and the solvent ethyl acetate in the obtained organic phase was removed to obtain 1.2 g of crude 4-nitrothioanisole, which was further purified to obtain 0.89 g of product 4-nitrothioanisole, with a yield of 69.0%;
反应物萃取旋蒸后脱除乙酸乙酯冷却至室温为胶状混合物,可通过精馏或重结晶对其进一步纯化。The reactants are extracted and rotary evaporated to remove ethyl acetate and cooled to room temperature to obtain a colloidal mixture, which can be further purified by distillation or recrystallization.
以上所述,仅是本发明的若干个具体实例。显然,本发明不限于以上实施例,还可以有许多变形。本领域的普通技术人员能从本发明公开的内容直接导出或联想到的所有变形,均应认为是本发明的保护范围。The above are only some specific examples of the present invention. Obviously, the present invention is not limited to the above embodiments, and there are many variations. All variations that can be directly derived or associated with the content disclosed by a person skilled in the art should be considered as the protection scope of the present invention.
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