WO2021212734A1 - Application of mixed n-heterocyclic carbene-based nickel (ii) complex in reaction for synthesizing 2-linear alkylbenzothiazole compound - Google Patents

Application of mixed n-heterocyclic carbene-based nickel (ii) complex in reaction for synthesizing 2-linear alkylbenzothiazole compound Download PDF

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WO2021212734A1
WO2021212734A1 PCT/CN2020/116941 CN2020116941W WO2021212734A1 WO 2021212734 A1 WO2021212734 A1 WO 2021212734A1 CN 2020116941 W CN2020116941 W CN 2020116941W WO 2021212734 A1 WO2021212734 A1 WO 2021212734A1
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reaction
linear alkyl
synthesizing
benzothiazole
catalyst
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孙宏枚
水雨
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苏州大学
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2265—Carbenes or carbynes, i.e.(image)
    • B01J31/2269—Heterocyclic carbenes
    • B01J31/2273—Heterocyclic carbenes with only nitrogen as heteroatomic ring members, e.g. 1,3-diarylimidazoline-2-ylidenes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
    • B01J31/185—Phosphites ((RO)3P), their isomeric phosphonates (R(RO)2P=O) and RO-substitution derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0225—Complexes comprising pentahapto-cyclopentadienyl analogues
    • B01J2531/0233—Aza-Cp ligands, i.e. [CnN(5-n)Rn]- in which n is 0-4 and R is H or hydrocarbyl, or analogous condensed ring systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/84—Metals of the iron group
    • B01J2531/847—Nickel
    • 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

Definitions

  • the invention belongs to the technical field of organic synthesis preparation, and specifically relates to a method for synthesizing 2-linear alkyl benzothiazole compounds.
  • Benzothiazole and its derivatives are a class of fused heterocyclic compounds containing nitrogen and sulfur. As an important leading framework with good biological activity, they are widely used in the creation of pesticides and medicines. In industry, these compounds can also be used as rubber vulcanization accelerators and plastic dyes (see Dai, XQ; Zhu, YB; Wang, ZY; Wong, JQ Chin. J. Org. Chem. 2017 , 37 , 1924) . Among them, with the discovery of 2-substituted benzothiazole units in various biologically active molecules such as antibacterial, insecticidal, and anticancer, more and more attention has been paid to the development of its synthetic methods.
  • the purpose of the present invention is to provide a new method for synthesizing 2-linear alkyl benzothiazole compounds, that is, the air-stabilized mixed nickel (II) complex Ni[P(OEt) 3 ][(RNCHCHNR) C]Br 2 is a catalyst, where R is 2,6-bis(diphenylmethyl)-4-methoxyphenyl, in the presence of metal magnesium, through aliphatic ⁇ -olefins and benzothiazole compounds Hydrogen heteroarylation reaction to synthesize 2-linear alkyl benzothiazole compounds, the catalyst cost, operability and substrate applicability are significantly better than the prior art.
  • the air-stabilized mixed nickel (II) complex Ni[P(OEt) 3 ][(RNCHCHNR) C]Br 2 is a catalyst, where R is 2,6-bis(diphenylmethyl)-4-methoxyphenyl, in the presence of metal magnesium, through aliphatic ⁇ -olefins and benzothiazo
  • the present invention adopts the following technical scheme:
  • the present invention discloses the application of a nitrogen heterocyclic carbene group mixed nickel (II) complex as a catalyst in the synthesis of 2-linear alkyl benzothiazole compounds.
  • the reaction substrate is a benzothiazole compound and aliphatic a-olefin; preferably, the synthesis of 2-linear alkyl benzothiazole compounds
  • the reaction is carried out in the presence of magnesium in an inert gas atmosphere.
  • the invention discloses a method for synthesizing 2-linear alkyl benzothiazole compounds.
  • the method includes the following steps. In an inert gas atmosphere, a catalyst, a metal magnesium, a benzothiazole compound, an aliphatic a-olefin and a solvent are sequentially added to react Obtain 2-linear alkyl benzothiazole compounds.
  • the chemical structure formula of the catalyst (nitrogen heterocyclic carbene group mixed nickel (II) complex) is as follows: .
  • R has the following structural formula: .
  • the reaction is terminated with water, and the reaction product is extracted with ethyl acetate, and separated and purified by column chromatography to obtain the product yield, which can be quantitatively analyzed.
  • the temperature of the reaction is 50-70°C, and the time is 1 to 5 hours.
  • the inert gas is argon; and the solvent is tetrahydrofuran.
  • the molar ratio of the catalyst, the metal magnesium, the benzothiazole compound, and the aliphatic a-olefin is 0.05 to 0.10:0.5:1:1.5.
  • the amount of aliphatic a-olefin is 1.5 times that of benzothiazole compounds, the amount of metal magnesium is 0.5 times that of benzothiazole compounds, and the amount of catalyst is benzothiazole compounds. 10% of the compound; the reaction temperature is 60°C, and the reaction time is 3 hours.
  • R 1 is one of hydrogen, 6-methyl, and 6-methoxy.
  • aliphatic a-olefins include 1-hexene, 1-heptene, 1-octene, 1-nonene, 1-decene, dodecene, tetradecene, hexadecene, 3,3- Dimethyl-1-butene, 4-phenyl-1-butene.
  • R 1 is derived from a benzothiazole compound
  • R 2 is derived from an aliphatic a-olefin.
  • the prior art uses a styrene compound as a substrate to react with a benzothiazole compound.
  • the reaction conditions involved are 80°C/60h, and the amount of magnesium is equivalent to the molar amount of the benzothiazole compound; the present invention uses 60°C to react for 3 hours and The amount of magnesium metal is half of the benzothiazole compound, which can catalyze the reaction of aliphatic a-olefins and benzothiazole compounds to form 2-linear alkyl benzothiazole compounds with a yield of 95%, which is unexpected Technical effect.
  • the present invention has the following advantages.
  • the low-cost, easy-to-obtain, air-stable mixed nickel (II) complex is used as a catalyst to realize the hydroheteroarylation of aliphatic a-olefins and benzothiazole compounds in the presence of magnesium
  • the reaction provides a new synthetic method for 2-linear alkyl benzothiazole compounds.
  • the preparation method disclosed in the present invention has mild reaction conditions, cheap and easy-to-obtain catalysts, good substrate applicability and 100% atomic economy, meets the requirements of green synthesis, and has great practical application value.
  • the method for synthesizing 2-linear alkyl benzothiazole compounds disclosed in the present invention is as follows. In an inert gas atmosphere, a catalyst, metal magnesium, benzothiazole compound, aliphatic a-olefin and solvent are sequentially added into a reaction flask. The reaction yields 2-linear alkyl benzothiazole compounds.
  • R has the following structural formula: .
  • Example 1 The divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of 1-hexene and benzothiazole: .
  • the catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), 1 -Hexene (93 ⁇ l, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvents, react at 60 o C for 3 hours, stop the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (with ethyl acetate The volume ratio of ester/petroleum ether is 1:10 as the developing agent, and the yield is 95%.
  • the amount of catalyst was reduced to 5 mol%, and the rest remained unchanged, and the yield of the product obtained according to the above method was 81%.
  • Example 1 The tri-divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of 1-heptene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol) was added to the reaction flask in sequence , 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), 1-heptene (106 ⁇ l, 0.75 mmol), tetrahydrofuran (1.5 ml) Solvent, react at 60 o C for 3 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:10 as the developing solvent). The rate is 94%.
  • Example Four Divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of 1-octene and benzothiazole: Under the protection of argon, a catalyst (66 mg, 0.05 mmol) is added to the reaction flask in sequence , 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), 1-octene (118 ⁇ l, 0.75 mmol), tetrahydrofuran (1.5 ml) Solvent, react at 60 o C for 3 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:10 as the developing solvent). The rate is 94%.
  • Example 5 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of 1-nonene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol) was added to the reaction flask in sequence , 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), 1-nonene (130 ⁇ l, 0.75 mmol), tetrahydrofuran (1.5 ml) Solvent, react at 60 o C for 3 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:10 as the developing solvent). The rate is 90%.
  • Example 6 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of 1-decene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol) was added to the reaction flask in sequence , 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), 1-decene (142 ⁇ l, 0.75 mmol), tetrahydrofuran (1.5 ml) Solvent, react at 60 o C for 5 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:10 as the developing solvent). The rate is 90%.
  • Example 7 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of dodecene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), dodecene (166 ⁇ l, 0.75 mmol), and tetrahydrofuran (1.5 ml) as solvents, React at 60 o C for 4 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using ethyl acetate/petroleum ether volume ratio 1:10 mixed solvent as the developing solvent), the yield is 92%.
  • Example 8 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of tetradecene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), tetradecene (190 ⁇ l, 0.75 mmol), and tetrahydrofuran (1.5 ml) as solvents, React at 60 o C for 5 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using ethyl acetate/petroleum ether volume ratio 1:10 mixed solvent as the developing solvent), the yield is 91%.
  • Example 9 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of hexadecene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), hexadecene (215 ⁇ l, 0.75 mmol), and tetrahydrofuran (1.5 ml) as solvents, React at 70 o C for 5 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using ethyl acetate/petroleum ether volume ratio 1:10 mixed solvent as the developing solvent), the yield is 90%.
  • Dodecavalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of 3,3-dimethyl-1-butene and benzothiazole: under the protection of argon, add sequentially to the reaction flask Catalyst (33 mg, 0.025 mmol, 5 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 ⁇ l, 0.5 mmol), 3,3-dimethyl-1-butene (97 ⁇ l, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 60 o C for 3 hours, stop the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (ethyl acetate/petroleum) A mixed solvent with an ether volume ratio of 1:10 is used as a developing agent, and the yield is 95%.
  • Catalyst 33 mg, 0.025 mmol, 5 mol
  • the present invention uses cheap and easily available divalent nickel (II) complexes as catalysts to realize the hydrogen heteroarylation reaction of aliphatic ⁇ -olefins and benzothiazole compounds under relatively mild conditions. It provides a new synthetic method with 100% atom economy for 2-linear alkylthiazole compounds, which has obvious practical application value.

Abstract

Disclosed in the present invention are an application of a mixed N-heterocyclic carbene-based nickel (II) complex in a reaction for synthesizing a 2-linear alkylbenzothiazole compound, and a method for synthesizing a 2-linear alkylbenzothiazole compound. A 2-linear alkylbenzothiazole compound is synthesized by a hydroheteroarylation reaction of an aliphatic α-olefin and a benzothiazole compound in the presence of magnesium by using as a catalyst a mixed nickel (II) complex having the molecular formula Ni[P(OEt) 3](RNCHCHNR)C]Br 2 , [R being 2,6-bis(diphenylmethyl)-4-methoxyphenyl]. Compared with existing methods, the present invention avoids the use of expensive monovalent rhodium complexes, and provides a novel method for preparing a 2-linear alkylbenzothiazole compound by means of the hydroheteroarylation reaction of an aliphatic α-olefin by using a divalent nickel catalyst.

Description

氮杂环卡宾基混配型镍(II)配合物在合成2-直链烷基苯并噻唑类化合物反应中的应用Application of Nitrogen Heterocyclic Carbenyl Mixed Ligand Nickel(II) Complex in the Synthesis of 2-Linear Alkyl Benzothiazole Compounds 技术领域Technical field
本发明属于有机合成制备技术领域，具体涉及到一种合成2-直链烷基苯并噻唑类化合物的方法。The invention belongs to the technical field of organic synthesis preparation, and specifically relates to a method for synthesizing 2-linear alkyl benzothiazole compounds.
背景技术Background technique
苯并噻唑及其衍生物是一类含氮、硫的稠杂环化合物，作为具有良好生物活性的重要先导骨架被广泛应用于农药及医药等药物创制中。在工业上,这类化合物还可用作橡胶硫化促进剂和塑料染色剂（参见Dai, X. Q.; Zhu, Y. B.; Wang, Z. Y.; Wong, J. Q. Chin. J. Org. Chem. 2017, 37, 1924）。其中，随着2-取代苯并噻唑单元在抗菌、杀虫、抗癌等各种生物活性分子中的发现, 对其合成方法的开发也受到了越来越多的关注。但是，目前关于在苯并噻唑的2位引入直链烷基的方法还是非常有限的，并且存在着明显的局限性。在公开的苯并杂环反应中，如吲哚类底物可以与芳基乙烯反应，但如1-辛烯类脂肪族α-烯烃是不能反应的（参见Wong, M. Y.; Yamakawa, T.; Yoshikai, N. Org. Lett. 2015, 17, 442）。本课题组利用混配型二价镍(II)配合物实现了苯并噻唑与芳基乙烯的氢杂芳基化反应，但反应用于芳基乙烯类底物，因此也无法提供2-直链烷基苯并噻唑类化合物。 Benzothiazole and its derivatives are a class of fused heterocyclic compounds containing nitrogen and sulfur. As an important leading framework with good biological activity, they are widely used in the creation of pesticides and medicines. In industry, these compounds can also be used as rubber vulcanization accelerators and plastic dyes (see Dai, XQ; Zhu, YB; Wang, ZY; Wong, JQ Chin. J. Org. Chem. 2017 , 37 , 1924) . Among them, with the discovery of 2-substituted benzothiazole units in various biologically active molecules such as antibacterial, insecticidal, and anticancer, more and more attention has been paid to the development of its synthetic methods. However, the current methods for introducing linear alkyl groups at the 2-position of benzothiazole are still very limited, and there are obvious limitations. In the disclosed benzoheterocyclic reaction, substrates such as indole can be reacted with arylethylene, but aliphatic α-olefins such as 1-octene cannot be reacted (see Wong, MY; Yamakawa, T.; Yoshikai, N. Org. Lett. 2015 , 17 , 442). Our research group used mixed-type divalent nickel (II) complexes to achieve the hydroheteroarylation reaction of benzothiazole and arylethylene, but the reaction was used for arylethylene substrates, so it was unable to provide 2-direction Alkyl benzothiazole compounds.
技术问题technical problem
本发明的目的是提供一种合成2-直链烷基苯并噻唑类化合物的新方法，即以空气稳定的混配型镍(II)配合物Ni[P(OEt) 3][(RNCHCHNR)C]Br 2为催化剂，其中R为2,6-二(二苯基甲基)-4-甲氧基苯基，在金属镁的存在下，通过脂肪族α-烯烃与苯并噻唑类化合物的氢杂芳基化反应来合成2-直链烷基苯并噻唑类化合物，催化剂成本、可操作性和底物适用性都要明显优于现有技术。 The purpose of the present invention is to provide a new method for synthesizing 2-linear alkyl benzothiazole compounds, that is, the air-stabilized mixed nickel (II) complex Ni[P(OEt) 3 ][(RNCHCHNR) C]Br 2 is a catalyst, where R is 2,6-bis(diphenylmethyl)-4-methoxyphenyl, in the presence of metal magnesium, through aliphatic α-olefins and benzothiazole compounds Hydrogen heteroarylation reaction to synthesize 2-linear alkyl benzothiazole compounds, the catalyst cost, operability and substrate applicability are significantly better than the prior art.
技术解决方案Technical solutions
本发明采用如下技术方案：本发明公开了氮杂环卡宾基混配型镍(II)配合物作为催化剂在合成2-直链烷基苯并噻唑类化合物反应中的应用。The present invention adopts the following technical scheme: The present invention discloses the application of a nitrogen heterocyclic carbene group mixed nickel (II) complex as a catalyst in the synthesis of 2-linear alkyl benzothiazole compounds.
进一步的，合成2-直链烷基苯并噻唑类化合物的反应中，反应底物为苯并噻唑化合物、脂肪族a-烯烃；优选的，合成2-直链烷基苯并噻唑类化合物的反应在镁存在下、在惰性气体气氛中进行。Further, in the reaction for the synthesis of 2-linear alkyl benzothiazole compounds, the reaction substrate is a benzothiazole compound and aliphatic a-olefin; preferably, the synthesis of 2-linear alkyl benzothiazole compounds The reaction is carried out in the presence of magnesium in an inert gas atmosphere.
本发明公开了合成2-直链烷基苯并噻唑类化合物的方法，包括以下步骤，在惰性气体气氛中，依次加入催化剂、金属镁、苯并噻唑化合物、脂肪族a-烯烃和溶剂，反应得到2-直链烷基苯并噻唑类化合物。The invention discloses a method for synthesizing 2-linear alkyl benzothiazole compounds. The method includes the following steps. In an inert gas atmosphere, a catalyst, a metal magnesium, a benzothiazole compound, an aliphatic a-olefin and a solvent are sequentially added to react Obtain 2-linear alkyl benzothiazole compounds.
本发明中，所述催化剂（氮杂环卡宾基混配型镍(II)配合物）的化学结构式如下：
Figure 454281dest_path_image001
。 In the present invention, the chemical structure formula of the catalyst (nitrogen heterocyclic carbene group mixed nickel (II) complex) is as follows:
Figure 454281dest_path_image001
.
R具有以下结构式：
Figure 105842dest_path_image002
。 R has the following structural formula:
Figure 105842dest_path_image002
.
上述技术方案中，反应结束后，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯，得到产物收率，可进行定量分析。In the above technical scheme, after the reaction is completed, the reaction is terminated with water, and the reaction product is extracted with ethyl acetate, and separated and purified by column chromatography to obtain the product yield, which can be quantitatively analyzed.
上述技术方案中，所述反应的温度为50～70℃，时间为1～5小时。In the above technical scheme, the temperature of the reaction is 50-70°C, and the time is 1 to 5 hours.
上述技术方案中，所述惰性气体为氩气；所述溶剂为四氢呋喃。In the above technical solution, the inert gas is argon; and the solvent is tetrahydrofuran.
上述技术方案中，催化剂、金属镁、苯并噻唑化合物、脂肪族a-烯烃的摩尔比为0.05～0.10∶0.5∶1∶1.5。In the above technical scheme, the molar ratio of the catalyst, the metal magnesium, the benzothiazole compound, and the aliphatic a-olefin is 0.05 to 0.10:0.5:1:1.5.
优选的技术方案中，以物质的量计，脂肪族a-烯烃的用量是苯并噻唑类化合物的1.5倍，金属镁的用量是苯并噻唑化合物的0.5倍，催化剂的用量是苯并噻唑类化合物的10 %；反应的温度是60℃，反应的时间为3小时。In the preferred technical solution, the amount of aliphatic a-olefin is 1.5 times that of benzothiazole compounds, the amount of metal magnesium is 0.5 times that of benzothiazole compounds, and the amount of catalyst is benzothiazole compounds. 10% of the compound; the reaction temperature is 60°C, and the reaction time is 3 hours.
本发明中，苯并噻唑化合物由下列化学结构式表达：
Figure 682317dest_path_image003
R 1为氢、6-甲基、6-甲氧基中的一种。 In the present invention, the benzothiazole compound is expressed by the following chemical structural formula:
Figure 682317dest_path_image003
R 1 is one of hydrogen, 6-methyl, and 6-methoxy.
脂肪族a-烯烃的化学结构式如下：
Figure 811947dest_path_image004
。 The chemical structural formula of aliphatic a-olefin is as follows:
Figure 811947dest_path_image004
.
具体的，脂肪族a-烯烃包括1-己烯、1-庚烯、1-辛烯、1-壬烯、1-癸烯、十二烯、十四烯、十六烯、3,3-二甲基-1-丁烯，4-苯基-1-丁烯。Specifically, aliphatic a-olefins include 1-hexene, 1-heptene, 1-octene, 1-nonene, 1-decene, dodecene, tetradecene, hexadecene, 3,3- Dimethyl-1-butene, 4-phenyl-1-butene.
2-直链烷基苯并噻唑类化合物的化学结构式如下：
Figure 626319dest_path_image005
。 The chemical structure of 2-linear alkyl benzothiazole compounds is as follows:
Figure 626319dest_path_image005
.
其中，R 1来自苯并噻唑化合物、R 2来自脂肪族a-烯烃。 Among them, R 1 is derived from a benzothiazole compound, and R 2 is derived from an aliphatic a-olefin.
本发明的技术方案可表示如下：
Figure 245520dest_path_image006
。 The technical scheme of the present invention can be expressed as follows:
Figure 245520dest_path_image006
.
现有技术以苯乙烯化合物为底物，与苯并噻唑化合物反应，涉及的反应条件为80℃/60h，且镁用量与苯并噻唑化合物的摩尔量等同；本发明采用60℃反应3小时且金属镁的用量是苯并噻唑化合物的一半，可以催化脂肪族a-烯烃与苯并噻唑类化合物反应生成2-直链烷基苯并噻唑类化合物，收率达到95%，具有预料不到的技术效果。The prior art uses a styrene compound as a substrate to react with a benzothiazole compound. The reaction conditions involved are 80°C/60h, and the amount of magnesium is equivalent to the molar amount of the benzothiazole compound; the present invention uses 60°C to react for 3 hours and The amount of magnesium metal is half of the benzothiazole compound, which can catalyze the reaction of aliphatic a-olefins and benzothiazole compounds to form 2-linear alkyl benzothiazole compounds with a yield of 95%, which is unexpected Technical effect.
有益效果Beneficial effect
由于上述技术方案的运用，本发明具有下列优点。Due to the application of the above technical solutions, the present invention has the following advantages.
1.  本发明首次以价廉易得、空气稳定的混配型镍(II)配合物为催化剂，在镁的存在下实现了脂肪族a-烯烃与苯并噻唑类化合物的氢杂芳基化反应，为2-直链烷基苯并噻唑类化合物提供了一种新的合成方法。1. In the present invention, for the first time, the low-cost, easy-to-obtain, air-stable mixed nickel (II) complex is used as a catalyst to realize the hydroheteroarylation of aliphatic a-olefins and benzothiazole compounds in the presence of magnesium The reaction provides a new synthetic method for 2-linear alkyl benzothiazole compounds.
2.  本发明公开的制备方法反应条件温和，催化剂价廉易得，具有较好的底物适用性和100%原子经济性，符合绿色合成的要求，实际应用价值大。2. The preparation method disclosed in the present invention has mild reaction conditions, cheap and easy-to-obtain catalysts, good substrate applicability and 100% atomic economy, meets the requirements of green synthesis, and has great practical application value.
本发明的实施方式Embodiments of the present invention
本发明公开的合成2-直链烷基苯并噻唑类化合物的方法如下，在惰性气体气氛中，在反应瓶中依次加入催化剂、金属镁、苯并噻唑化合物、脂肪族a-烯烃和溶剂，反应得到2-直链烷基苯并噻唑类化合物。The method for synthesizing 2-linear alkyl benzothiazole compounds disclosed in the present invention is as follows. In an inert gas atmosphere, a catalyst, metal magnesium, benzothiazole compound, aliphatic a-olefin and solvent are sequentially added into a reaction flask. The reaction yields 2-linear alkyl benzothiazole compounds.
下面结合实施例对本发明作进一步描述：实施例一 参见CN108002966A，催化剂氮杂环卡宾基混配型镍(II)配合物Ni[P(OEt) 3][(RNCHCHNR)C]Br 2的化学结构式如下，用于以下实施例：
Figure 246974dest_path_image007
。 The present invention will be further described in conjunction with the following examples: For example one, see CN108002966A, the chemical structure formula of the catalyst nitrogen heterocyclic carbenyl mixed nickel (II) complex Ni[P(OEt) 3 ][(RNCHCHNR)C]Br 2 As follows, used in the following examples:
Figure 246974dest_path_image007
.
R具有以下结构式：
Figure 445874dest_path_image008
。 R has the following structural formula:
Figure 445874dest_path_image008
.
实施例二 二价镍(II)配合物为催化剂，催化1-己烯与苯并噻唑的氢杂芳基化反应：
Figure 911490dest_path_image009
。 Example The divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of 1-hexene and benzothiazole:
Figure 911490dest_path_image009
.
氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、1-己烯（93微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应3小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为95%。 Under the protection of argon, the catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), 1 -Hexene (93 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvents, react at 60 o C for 3 hours, stop the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (with ethyl acetate The volume ratio of ester/petroleum ether is 1:10 as the developing agent, and the yield is 95%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3): δ 7.98 (d, J = 8.3 Hz, 1H), 7.85 – 7.80 (m, 1H), 7.45 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.38 – 7.32 (m, 1H), 3.15 – 3.10 (t, J = 7.5 Hz, 2H), 1.87 (p, J = 7.6 Hz, 2H), 1.49 – 1.28 (m, 6H), 0.93 – 0.85 (m, 3H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, and measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.98 (d, J = 8.3 Hz , 1H), 7.85 – 7.80 (m, 1H), 7.45 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.38 – 7.32 (m, 1H), 3.15 – 3.10 (t, J = 7.5 Hz, 2H ), 1.87 (p, J = 7.6 Hz, 2H), 1.49 – 1.28 (m, 6H), 0.93 – 0.85 (m, 3H).
将60℃提高到80℃，其余不变，根据上述方法得到的产物产率为88%。Increasing 60°C to 80°C, and the rest unchanged, the yield of the product obtained according to the above method is 88%.
将催化剂用量降为5mol%，其余不变，根据上述方法得到的产物产率为81%。The amount of catalyst was reduced to 5 mol%, and the rest remained unchanged, and the yield of the product obtained according to the above method was 81%.
实施例三 二价镍(II)配合物为催化剂，催化1-庚烯与苯并噻唑的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、1-庚烯（106微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应3小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为94%。 Example The tri-divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of 1-heptene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol) was added to the reaction flask in sequence , 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), 1-heptene (106 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) Solvent, react at 60 o C for 3 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:10 as the developing solvent). The rate is 94%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3): δ 7.97 (d, J = 8.3 Hz, 1H), 7.87 – 7.80 (m, 1H), 7.46 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.40 – 7.35 (m, 1H), 3.15 – 3.10 (t, J = 7.5 Hz, 2H), 1.85 (p, J = 7.6 Hz, 2H), 1.39 – 1.28 (m, 8H), 0.92 – 0.85 (m, 3H)。 The product was dissolved in CDCl 3 (approximately 0.4 mL), the tube was sealed, and it was measured and characterized on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.97 (d, J = 8.3 Hz , 1H), 7.87 – 7.80 (m, 1H), 7.46 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.40 – 7.35 (m, 1H), 3.15 – 3.10 (t, J = 7.5 Hz, 2H ), 1.85 (p, J = 7.6 Hz, 2H), 1.39 – 1.28 (m, 8H), 0.92 – 0.85 (m, 3H).
实施例四 二价镍(II)配合物为催化剂，催化1-辛烯与苯并噻唑的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、1-辛烯（118微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应3小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为94%。 Example Four: Divalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of 1-octene and benzothiazole: Under the protection of argon, a catalyst (66 mg, 0.05 mmol) is added to the reaction flask in sequence , 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), 1-octene (118 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) Solvent, react at 60 o C for 3 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:10 as the developing solvent). The rate is 94%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3): δ 7.99 (d, J = 8.2 Hz, 1H), 7.88 – 7.80 (m, 1H), 7.45 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.38 – 7.32 (m, 1H), 3.16 – 3.09 (t, J = 7.5 Hz, 2H), 1.89 (p, J = 7.6 Hz, 2H), 1.49 – 1.28 (m, 10H), 0.93 – 0.87 (m, 3H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.99 (d, J = 8.2 Hz , 1H), 7.88 – 7.80 (m, 1H), 7.45 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.38 – 7.32 (m, 1H), 3.16 – 3.09 (t, J = 7.5 Hz, 2H ), 1.89 (p, J = 7.6 Hz, 2H), 1.49 – 1.28 (m, 10H), 0.93 – 0.87 (m, 3H).
对比例：氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、苯乙烯（86微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应3小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为10%，可认为不反应。 Comparative example: Under the protection of argon, the catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), and benzothiazole (54 μl, 0.5 mmol) were sequentially added to the reaction flask under the protection of argon. ), styrene (86 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvents, react at 60 o C for 3 hours, stop the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (with acetic acid The mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:10 is used as a developing agent, and the yield is 10%, which can be considered as non-reactive.
实施例五 二价镍(II)配合物为催化剂，催化1-壬烯与苯并噻唑的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、1-壬烯（130微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应3小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为90%。 Example 5 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of 1-nonene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol) was added to the reaction flask in sequence , 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), 1-nonene (130 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) Solvent, react at 60 o C for 3 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:10 as the developing solvent). The rate is 90%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3): δ 7.99 (d, J = 8.2 Hz, 1H), 7.88 – 7.80 (m, 1H), 7.45 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.38 – 7.32 (m, 1H), 3.16 – 3.09 (t, J = 7.5 Hz, 2H), 1.89 (p, J = 7.6 Hz, 2H), 1.49 – 1.25 (m, 12H), 0.95 – 0.83 (m, 3H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.99 (d, J = 8.2 Hz , 1H), 7.88 – 7.80 (m, 1H), 7.45 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.38 – 7.32 (m, 1H), 3.16 – 3.09 (t, J = 7.5 Hz, 2H ), 1.89 (p, J = 7.6 Hz, 2H), 1.49 – 1.25 (m, 12H), 0.95 – 0.83 (m, 3H).
实施例六 二价镍(II)配合物为催化剂，催化1-葵烯与苯并噻唑的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、1-葵烯（142微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应5小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为90%。 Example 6 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of 1-decene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol) was added to the reaction flask in sequence , 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), 1-decene (142 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) Solvent, react at 60 o C for 5 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using a mixed solvent of ethyl acetate/petroleum ether volume ratio of 1:10 as the developing solvent). The rate is 90%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3):δ 7.99 (d, J = 7.5 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.49 – 7.42 (m, 1H), 7.34 (td, J = 7.7, 1.2 Hz, 1H), 3.17 – 3.07 (t, J = 7.5 Hz, 2H), 1.89 (p, J = 7.6 Hz, 2H), 1.49 – 1.26 (m, 14H), 0.90 (t, J = 6.8 Hz, 3H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, and measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.99 (d, J = 7.5 Hz , 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.49 – 7.42 (m, 1H), 7.34 (td, J = 7.7, 1.2 Hz, 1H), 3.17 – 3.07 (t, J = 7.5 Hz, 2H), 1.89 (p, J = 7.6 Hz, 2H), 1.49 – 1.26 (m, 14H), 0.90 (t, J = 6.8 Hz, 3H).
实施例七 二价镍(II)配合物为催化剂，催化十二烯与苯并噻唑的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、十二烯（166微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应4小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为92%。 Example 7 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of dodecene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), dodecene (166 μl, 0.75 mmol), and tetrahydrofuran (1.5 ml) as solvents, React at 60 o C for 4 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using ethyl acetate/petroleum ether volume ratio 1:10 mixed solvent as the developing solvent), the yield is 92%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3):δ 7.99 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.49 – 7.43 (m, 1H), 7.39 – 7.32 (m, 1H), 3.16 – 3.10 (t, J = 7.5 Hz, 2H), 1.90 (p, J = 7.6 Hz, 2H), 1.48 – 1.27 (m, 18H), 0.91 (t, J = 6.7 Hz, 3H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, and measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.99 (d, J = 8.2 Hz , 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.49 – 7.43 (m, 1H), 7.39 – 7.32 (m, 1H), 3.16 – 3.10 (t, J = 7.5 Hz, 2H), 1.90 ( p, J = 7.6 Hz, 2H), 1.48 – 1.27 (m, 18H), 0.91 (t, J = 6.7 Hz, 3H).
实施例八 二价镍(II)配合物为催化剂，催化十四烯与苯并噻唑的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、十四烯（190微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应5小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为91%。 Example 8 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of tetradecene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), tetradecene (190 μl, 0.75 mmol), and tetrahydrofuran (1.5 ml) as solvents, React at 60 o C for 5 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using ethyl acetate/petroleum ether volume ratio 1:10 mixed solvent as the developing solvent), the yield is 91%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3):δ 7.97 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.49 – 7.43 (m, 1H), 7.39 – 7.32 (m, 1H), 3.15 – 3.10 (t, J = 7.5 Hz, 2H), 1.89 (p, J = 7.6 Hz, 2H), 1.45 – 1.27 (m, 22H), 0.89 (t, J = 6.7 Hz, 3H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, and measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.97 (d, J = 8.2 Hz , 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.49 – 7.43 (m, 1H), 7.39 – 7.32 (m, 1H), 3.15 – 3.10 (t, J = 7.5 Hz, 2H), 1.89 ( p, J = 7.6 Hz, 2H), 1.45 – 1.27 (m, 22H), 0.89 (t, J = 6.7 Hz, 3H).
实施例九 二价镍(II)配合物为催化剂，催化十六烯与苯并噻唑的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（66毫克，0.05毫摩尔，10 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、十六烯（215微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于70 oC下反应5小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为90%。 Example 9 The divalent nickel (II) complex was used as a catalyst to catalyze the hydroheteroarylation reaction of hexadecene and benzothiazole: under the protection of argon, a catalyst (66 mg, 0.05 mmol, 10 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), hexadecene (215 μl, 0.75 mmol), and tetrahydrofuran (1.5 ml) as solvents, React at 70 o C for 5 hours, terminate the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (using ethyl acetate/petroleum ether volume ratio 1:10 mixed solvent as the developing solvent), the yield is 90%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3): δ 7.99 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.49 – 7.43 (m, 1H), 7.39 – 7.32 (m, 1H), 3.16 – 3.10 (t, J = 7.5 Hz, 2H), 1.90 (p, J = 7.6 Hz, 2H), 1.48 – 1.27 (m, 26H), 0.91 (t, J = 6.7 Hz, 3H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.99 (d, J = 8.2 Hz , 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.49 – 7.43 (m, 1H), 7.39 – 7.32 (m, 1H), 3.16 – 3.10 (t, J = 7.5 Hz, 2H), 1.90 ( p, J = 7.6 Hz, 2H), 1.48 – 1.27 (m, 26H), 0.91 (t, J = 6.7 Hz, 3H).
实施例十 二价镍(II)配合物为催化剂，催化3,3-二甲基-1-丁烯与苯并噻唑的氢杂芳基化反应：氩气保护下，在反应瓶中依次加入催化剂（33毫克，0.025毫摩尔，5 mol%）、镁屑（6.0毫克，0.25毫摩尔）、苯并噻唑（54微升，0.5毫摩尔）、3,3-二甲基-1-丁烯（97微升，0.75毫摩尔）、四氢呋喃（1.5毫升）作溶剂，于60 oC下反应3小时，用水终止反应，反应产物用乙酸乙酯萃取，柱层析提纯（以乙酸乙酯/石油醚体积比为1∶10的混合溶剂为展开剂），产率为95%。 Example Dodecavalent nickel (II) complex is used as a catalyst to catalyze the hydroheteroarylation reaction of 3,3-dimethyl-1-butene and benzothiazole: under the protection of argon, add sequentially to the reaction flask Catalyst (33 mg, 0.025 mmol, 5 mol%), magnesium chips (6.0 mg, 0.25 mmol), benzothiazole (54 μl, 0.5 mmol), 3,3-dimethyl-1-butene (97 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 60 o C for 3 hours, stop the reaction with water, extract the reaction product with ethyl acetate, and purify by column chromatography (ethyl acetate/petroleum) A mixed solvent with an ether volume ratio of 1:10 is used as a developing agent, and the yield is 95%.
将产物溶于CDCl 3中（约0.4 mL），封管，室温下于Unity Inova-400型NMR仪上测定表征： 1H NMR (400 MHz, CDCl 3): δ 7.99 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.49 – 7.41 (m, 1H), 7.34 (t, J = 7.6 Hz, 1H), 3.18 – 3.05 (m, 2H), 1.93 – 1.68 (m, 2H), 1.02 (s, 9H)。 Dissolve the product in CDCl 3 (about 0.4 mL), seal the tube, measure and characterize it on a Unity Inova-400 NMR instrument at room temperature: 1 H NMR (400 MHz, CDCl 3 ): δ 7.99 (d, J = 8.2 Hz , 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.49 – 7.41 (m, 1H), 7.34 (t, J = 7.6 Hz, 1H), 3.18 – 3.05 (m, 2H), 1.93 – 1.68 ( m, 2H), 1.02 (s, 9H).
因此，本发明利用廉价易得的二价镍(II)配合物为催化剂，在相对温和的条件下实现脂肪族α-烯烃与苯并噻唑类化合物的氢杂芳基化反应具有独创性，可以为2-直链烷基噻唑类化合物提供具有100%的原子经济性的新合成方法，具有显而易见的实际应用价值。Therefore, the present invention uses cheap and easily available divalent nickel (II) complexes as catalysts to realize the hydrogen heteroarylation reaction of aliphatic α-olefins and benzothiazole compounds under relatively mild conditions. It provides a new synthetic method with 100% atom economy for 2-linear alkylthiazole compounds, which has obvious practical application value.

Claims (10)

  1. 氮杂环卡宾基混配型镍(II)配合物作为催化剂在合成2-直链烷基苯并噻唑类化合物反应中的应用；所述氮杂环卡宾基混配型镍(II)配合物的化学结构式如下：Application of nitrogen heterocyclic carbene-based mixed nickel (II) complex as a catalyst in the synthesis of 2-linear alkyl benzothiazole compounds; the nitrogen heterocyclic carbene-based mixed nickel (II) complex The chemical structure of is as follows:
    Figure dest_path_image001
    Figure dest_path_image001
    R具有以下结构式：R has the following structural formula:
    Figure dest_path_image002
    。
    Figure dest_path_image002
    .
  2. 根据权利要求1所述的应用，其特征在于，合成2-直链烷基苯并噻唑类化合物的反应中，反应底物为苯并噻唑化合物、脂肪族a-烯烃。The application according to claim 1, characterized in that, in the reaction of synthesizing 2-linear alkyl benzothiazole compounds, the reaction substrates are benzothiazole compounds and aliphatic a-olefins.
  3. 根据权利要求1所述的应用，其特征在于，合成2-直链烷基苯并噻唑类化合物的反应在镁存在下、在惰性气体气氛中进行。The application according to claim 1, wherein the reaction for synthesizing 2-linear alkyl benzothiazole compounds is carried out in the presence of magnesium in an inert gas atmosphere.
  4. 根据权利要求1所述的应用，其特征在于，所述反应的温度为50～70℃，时间为1～5小时。The application according to claim 1, wherein the temperature of the reaction is 50-70°C, and the time is 1 to 5 hours.
  5. 一种合成2-直链烷基苯并噻唑类化合物的方法，其特征在于，包括以下步骤，在惰性气体气氛中，混合催化剂、金属镁、苯并噻唑化合物、脂肪族a-烯烃和溶剂，反应得到2-直链烷基苯并噻唑类化合物；所述催化剂的化学结构式如下：A method for synthesizing 2-linear alkyl benzothiazole compounds, characterized in that it comprises the following steps, in an inert gas atmosphere, mixing a catalyst, a metal magnesium, a benzothiazole compound, an aliphatic a-olefin and a solvent, The reaction obtains 2-linear alkyl benzothiazole compounds; the chemical structural formula of the catalyst is as follows:
    Figure dest_path_image003
     
    Figure dest_path_image003
    R具有以下结构式：R has the following structural formula:
    Figure dest_path_image004
    。
    Figure dest_path_image004
    .
  6. 根据权利要求5所述合成2-直链烷基苯并噻唑类化合物的方法，其特征在于，反应结束后，用水终止反应，反应产物用乙酸乙酯萃取，通过柱层析分离提纯，得到产物。The method for synthesizing 2-linear alkyl benzothiazoles according to claim 5, characterized in that, after the reaction, the reaction is terminated with water, the reaction product is extracted with ethyl acetate, and the product is separated and purified by column chromatography to obtain the product .
  7. 根据权利要求5所述合成2-直链烷基苯并噻唑类化合物的方法，其特征在于，催化剂、金属镁、苯并噻唑化合物、脂肪族a-烯烃的摩尔比为0.05～0.10∶0.5∶1∶1.5。The method for synthesizing 2-linear alkyl benzothiazole compounds according to claim 5, wherein the molar ratio of the catalyst, metal magnesium, benzothiazole compound, and aliphatic a-olefin is 0.05 to 0.10:0.5: 1:1.5.
  8. 根据权利要求5所述合成2-直链烷基苯并噻唑类化合物的方法，其特征在于，所述反应的温度为50～70℃，时间为1～5小时。The method for synthesizing 2-linear alkyl benzothiazole compounds according to claim 5, characterized in that the reaction temperature is 50-70°C, and the time is 1-5 hours.
  9. 根据权利要求8所述合成2-直链烷基苯并噻唑类化合物的方法，其特征在于，所述反应的温度为60℃，时间为3小时。The method for synthesizing 2-linear alkyl benzothiazole compounds according to claim 8, wherein the temperature of the reaction is 60° C. and the time is 3 hours.
  10. 根据权利要求5所述合成2-直链烷基苯并噻唑类化合物的方法合成的2-直链烷基苯并噻唑类化合物。A 2-linear alkyl benzothiazole compound synthesized according to the method for synthesizing a 2-linear alkyl benzothiazole compound according to claim 5.
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