2527-66-4Relevant articles and documents
Synthesis method of N-alkane-1, 2-benzisothiazoline-3-ketone
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Paragraph 0039-0041, (2021/04/10)
The invention discloses a synthetic method of N-alkane-1,2-benzisothiazoline-3-ketone, which comprises the following steps: (1) under the protection of nitrogen, mixing and stirring phenyl sulfur chloride and a solvent; (2) dropwise adding alkyl carbamyl chloride; (3) slowly heating until hydrogen chloride is released and the system becomes turbid from clear and then becomes clear again; (4) mixing and stirring a catalyst and the solvent, keeping the temperature, and dropwise adding the mixture; (5) after dropwise adding, heating the system to 90 DEG C, keeping the temperature for 2 hours, and detecting that the BIT intermediate residue is less than 0.5% by HPLC; and (6) cooling to 30-40 DEG C, adding water while stirring, standing for layering, and carrying out reduced pressure distillation on the upper organic layer to obtain the N-alkane 1, 2-benzisothiazoline-3-ketone. The method has the advantages of cheap raw materials, low process difficulty, simple process flow, less wastewater amount, high yield, less solid waste, environmental friendliness and the like.
Novel synthesis method of N-substituted benzisothiazoline-3-ketone derivative
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Paragraph 0044-0046, (2020/07/02)
The invention discloses a novel synthesis method of an N-substituted benzisothiazoline-3-ketone derivative. The preparation method comprises the following steps: by taking a dithiosalicylic acid derivative and sulfur as raw materials, introducing chlorine or bromine to obtain a halogenated thiobenzoyl halide derivative, then preferably dropwise adding a mixed solution of primary amine and tertiaryamine, and carrying out reaction and ring closing to obtain the N-substituted benzisothiazole-3-ketone. The method disclosed by the invention is simple in process, safe and controllable, and easy forindustrial large-scale production.
Synthetic method 1-2 - benzisothiazol -3 -one compound (by machine translation)
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, (2020/09/09)
The invention discloses a synthetic method of 1-2 - benzisothiazol -3 -one compound, and belongs to the field of chemical synthesis. 2 - 1-benzisothiazol 2 -one compounds are synthesized through acid chlorination, amidation and cyclization reaction by using the sulfenyl-substituted benzoic acid extracted from BIT process -3 - waste water as a starting raw material. The method disclosed by the invention has the advantages of mild reaction conditions, simple and convenient operation, strong practicability, less waste water, high product purity and the like, and is suitable for large-scale industrial production. The technical scheme provided by the invention is resource utilization and preparation 1 of wastewater extract produced in BIT production, and a feasible method is provided for the 2 -benzisothiazol -3 -one compound. (by machine translation)
Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines
Castelli, Riccardo,Scalvini, Laura,Vacondio, Federica,Lodola, Alessio,Anselmi, Mattia,Vezzosi, Stefano,Carmi, Caterina,Bassi, Michele,Ferlenghi, Francesca,Rivara, Silvia,M?ller, Ingvar R.,Rand, Kasper D.,Daglian, Jennifer,Wei, Don,Dotsey, Emmanuel Y.,Ahmed, Faizy,Jung, Kwang-Mook,Stella, Nephi,Singh, Simar,Mor, Marco,Piomelli, Daniele
, p. 1261 - 1280 (2019/12/25)
We describe a set of benzisothiazolinone (BTZ) derivatives that are potent inhibitors of monoacylglycerol lipase (MGL), the primary degrading enzyme for the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Structure-activity relationship studies evaluated various substitutions on the nitrogen atom and the benzene ring of the BTZ nucleus. Optimized derivatives with nanomolar potency allowed us to investigate the mechanism of MGL inhibition. Site-directed mutagenesis and mass spectrometry experiments showed that BTZs interact in a covalent reversible manner with regulatory cysteines, Cys201 and Cys208, causing a reversible sulfenylation known to modulate MGL activity. Metadynamics simulations revealed that BTZ adducts favor a closed conformation of MGL that occludes substrate recruitment. The BTZ derivative 13 protected neuronal cells from oxidative stimuli and increased 2-AG levels in the mouse brain. The results identify Cys201 and Cys208 as key regulators of MGL function and point to the BTZ scaffold as a useful starting point for the discovery of allosteric MGL inhibitors.
Pipeline type continuous production method of 3-isothiazolinone compound
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Paragraph 0023, (2019/12/02)
The invention discloses a pipeline type continuous production method of a 3-isothiazolinone compound, which comprises the following steps: carrying out mixed reaction on a thioamide compound, a catalyst, a solvent and chlorine through a pipeline reactor system, and carrying out after-treatment after the reaction is completed to obtain the 3-isothiazolinone compound. According to the method, the defects of large occupied area, small productivity, low efficiency, high energy consumption and small safety coefficient caused by existing batch production of the 3-isothiazolinone compound are overcome; the invention provides a mode for continuously producing the 3-isothiazolinone compound, so that the reaction process is easy to control, energy consumption is reduced, the production efficiency and the safety coefficient of the production process are improved, and the process is an efficient and energy-saving safe production process.
Ebsulfur as a potent scaffold for inhibition and labelling of New Delhi metallo-β-lactamase-1 in vitro and in vivo
Su, Jianpeng,Liu, Jiayun,Chen, Cheng,Zhang, Yuejuan,Yang, Kewu
, p. 192 - 201 (2018/12/02)
The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has grown into an emerging threat, labelling and inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. Here, we report a potent covalent scaffold, ebsulfur, for targeting the protein in vitro and in vivo. Enzymatic kinetic study indicated that eighteen ebsulfurs gained except 1a–b and 1f inhibited NDM-1, exhibiting an IC50 value ranging of 0.16–9 μM, and 1g was found to be the best, dose- and time-dependent inhibitor with an IC50 of 0.16 μM. Also, these ebsulfurs effectively restored the antibacterial activity of cefazolin against E. coli expressing NDM-1, and the best effect was observed to be from 1g, 1i and 1n, resulting in an 256-fold reduction in MIC of the antibiotic at a dose of 16 μg/mL. The equilibrium dialysis study implied that the ebsulfur disrupted the coordination of one Zn(II) ion at active site of NDM-1. Labelling of NDM-1 using a constructed fluorescent ebsulfur Ebs-R suggested that the inhibitor covalently bound to the target through SDS-PAGE analysis in vitro. Also, labelling NDM-1 in living E. coli cells with Ebs-R by confocal microscopic imaging showed the real-time distribution change process of intracellular recombinant protein NDM-1. Moreover, the cytotoxicity of these ebsulfurs against L929 mouse fibroblastic cells was tested, and their capability to restore antibacterial activity of antibiotic against clinical strains E. coli EC08 producing NDM-1 was determined. The ebsulfur scaffold proposed here is valuable for development of the covalent irreversible inhibitors of NDM-1, and also for labelling the target in vitro and in vivo.
A MBIT BIT and method of production
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Paragraph 0039; 0047-0051, (2019/06/27)
The invention discloses a method for coproducing BIT (1,2-benzisothiazoline-3-ketone) and MBIT (2-methyl-1,2-benzisothiazoline-3-ketone). The method comprises the following steps: 1) performing hydrolytic cyclization reaction on o-methylthiocyanophenyl serving as a raw material, water and chlorine, filtering and salifying the reaction liquid after the reaction to obtain a BIT salt aqueous solution, acidizing and filtering to obtain a BIT product, and absorbing, pressurizing and condensing a byproduct methane chloride generated in the reaction process to collect for later use; 2) adding the BIT salt aqueous solution obtained in the step 1) into a high-pressure kettle, adding the byproduct methane chloride obtained in the step 1), and performing temperature-increasing reaction to obtain a mixture containing the MBIT and a byproduct MOBIT (3-methoxyl-1,2-benzisothiazoline); 3) adding the mixture containing the MBIT and the byproduct MOBIT and obtained in the step 2) into the hydrolytic cyclization reaction in the step 1), performing demethylating reaction on the byproduct MOBIT to change into BIT and methane chloride, combining the MBIT with hydrogen chloride to form MBIT hydrochloride, and performing separation steps such as filtering and neutralizing on the reaction mixture to obtain BIT and MBIT products separately. The method has the advantages of reasonable process, energy saving, low pollution, capability of greatly reducing production cost and the like.
Synthetic method of N-methyl-1,2-benzoisothiazolin-3-one
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Paragraph 0021; 0022; 0023; 0024; 0026-0027; 0029-0030, (2018/10/19)
The invention provides a synthetic method of N-methyl-1,2-benzoisothiazolin-3-one. The synthetic method of N-methyl-1,2-benzoisothiazolin-3-one comprises the following steps: step one, feeding methylchloride in a first system which is formed by 1,2-benzoisothiazolin-3-one, liquid caustic soda and water, stopping feeding the methyl chloride until the content of 1,2-benzisothiazole-3-one in a mixture is 1% or below, cooling and standing for layering, and collecting an upper organic layer; and step two, collecting an upper water layer, adding the 1,2-benzisothiazole-3-one, caustic soda flakes and a composite catalyst in the upper water layer to form a second system, heating and feeding the methyl chloride until the content of the 1,2-benzoisothiazolin-3-one is 1% or below, cooling and standing for layering, and distilling the upper organic layer under reduced pressure; and collecting a lower water layer of the second system and repeating step two. The reaction steps are less, and the route is short; raw materials are low and easily obtained, and the cost is reduced; the raw materials and by-products are odorless or has small odor, and are environmentally friendly; and a large amountof waste liquid is avoided, and thus, the pressure for environmental protection of enterprises is relieved.
Benzisothiazol-3-ones through a Metal-Free Intramolecular N–S Bond Formation
Yang, Ke,Zhang, Hao,Niu, Ben,Tang, Tiandi,Ge, Haibo
supporting information, p. 5520 - 5523 (2018/10/26)
The highly efficient synthesis of benzoisothiazol-3-ones from thiobenzamides has been described with good functional group compatibility and excellent yields. This work represents the first example of selectfluor-promoted N–S bond formation processes. This method provides a facile approach to access various important bioactive benzoisothiazol-3-ones.
An efficient approach to construct benzisothiazol-3(2: H)-ones via copper-catalyzed consecutive reaction of 2-halobenzamides and carbon disulfide
Li, Ting,Yang, Lei,Ni, Kaidong,Shi, Zhenyu,Li, Fei,Chen, Dongyin
, p. 6297 - 6303 (2016/07/11)
An efficient copper-catalyzed reaction for the synthesis of benzisothiazol-3(2H)-ones has been developed, starting from easily available 2-halobenzamides and carbon disulfide, which gave the corresponding target products in 30-89% yield for 25 examples. The reaction proceeds via a consecutive process with S-C bond and S-N bond formation.
