- Facile synthesis and in vitro activity of n-substituted 1,2-benzisothiazol-3(2H)-ones against dengue virus NS2BNS3 protease
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Several new N-substituted 1,2-benzisothiazol-3(2H)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties. Thus, the synthesised BITs were tested for inhibitory activity against the recombinant dengue virus serotype-2 (DENV-2) NS2BNS3 protease. Dose–response experiments and computational docking analyses revealed that several BITs bind to the protease in the vicinity of the catalytic triad with IC50 values in the micromolar range. The DENV2 infection assay showed that two BITs, 2-(2-chlorophenyl)benzo[d]isothiazol-3(2H)-one and 2-(2,6-dichlorophenyl)benzo[d]isothiazol-3(2H)-one, could suppress DENV replication and virus infectivity. These results indicate the potential of BITs for developing new anti-dengue therapeutics.
- Batool, Farwa,Saeed, Muhammad,Saleem, Hafiza Nosheen,Kirschner, Luisa,Bodem, Jochen
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- Synthesis method of N-alkane-1, 2-benzisothiazoline-3-ketone
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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.
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Paragraph 0036-0038
(2021/04/10)
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- Method for synthesizing 2-butyl-1, 2-benzisothiazoline-3-ketone
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The invention discloses a method for synthesizing 2-butyl-1, 2-benzisothiazoline-3-ketone. The method comprises the following steps: reacting n-butylamine with a chlorobenzene solution of triethylamine 25% o-methylthiobenzoyl chloride to obtain a mixed solution of N-butyl o-methylthiobenzamide, and filtering the mixed solution of N-butyl o-methylthiobenzamide, and obtaining chlorobenzene solutionand solids of N-butyl o-methylthiobenzamide, reacting the solid with liquid caustic soda to obtain triethylamine, reacting the chlorobenzene solution of N-butyl o-methylthiobenzamide with water, and carrying out reduced pressure distillation to separate chlorobenzene. The method has the advantages of simple process steps, low cost, high yield, recyclability and the like.
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Paragraph 0044-0049
(2021/02/06)
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- Synthetic method 1-2 - benzisothiazol -3 -one compound (by machine translation)
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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)
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- Novel synthesis method of N-substituted benzisothiazoline-3-ketone derivative
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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.
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Paragraph 0050-0052
(2020/07/02)
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- Pipeline type continuous production method of 3-isothiazolinone compound
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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.
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Paragraph 0022
(2019/12/02)
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- Domino Reactions Initiated by Copper-Catalyzed Aryl-I Bond Thiolation For the Switchable Synthesis of 2,3-Dihydrobenzothiazinones and Benzoisothiazolones
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The three-component reactions of o-iodobenzamides, elemental sulfur and dichloromethane (DCM) providing 2,3-dihydro-4H-benzo[e][1,3]thiazin-4-ones (2,3-dihydrobenzothiazinones) are accomplished via copper-catalyzed aryl C?I thiolation and subsequent N-, S-hetero ring formation. In addition, the in situ aryl C?I bond thiolation is also employed for the switchable synthesis of benzo[d]isothiazol-3(2H)-ones (benzoisothiazolones) by subjecting o-iodobenzamides, elemental sulfur to the copper-catalyzed condition with microwave irradiation. (Figure presented.).
- Xiong, Jin,Zhong, Guofeng,Liu, Yunyun
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supporting information
p. 550 - 555
(2018/12/14)
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- Novel synthesis method of 2-butyl-1,2-benzothiazol-3-one
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The invention relates to the technical field of fine chemical engineering, and discloses a novel synthesis method of 2-butyl-1,2-benzothiazol-3-one. The method comprises the following specific steps:allowing N-butyl-2-methyl(thiobenzamide) to react with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) in the presence of N,N-dimethyl-formamide for six hours at 60 DEGC, so as to obtain 2-butyl-1,2-benzothiazol-3-one. Compared with the prior art, the method has the advantages that no metal ions or chlorine-containing toxic reagents are introduced, and the yield ishigh, the operation is simple, the influence on the environment is small, the potential industrial value is achieved, and the method is worthy of popularization and application.
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Paragraph 0010; 0011; 0012; 0013; 0014; 0015; 0016
(2018/11/27)
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- Benzisothiazol-3-ones through a Metal-Free Intramolecular N–S Bond Formation
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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.
- Yang, Ke,Zhang, Hao,Niu, Ben,Tang, Tiandi,Ge, Haibo
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supporting information
p. 5520 - 5523
(2018/10/26)
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- 2-butyl-1,2-benzisothiazolin-3-one preparation method
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The present invention discloses a 2-butyl-1,2-benzisothiazolin-3-one synthesis process, which comprises that (1) a starting raw material BIT reacts with an alkali to form a BIT salt; and (2) the BIT salt reacts with halogenated n-butane to obtain the target product 2-butyl-1,2-benzisothiazolin-3-one (BBIT). The present invention further discloses a separation and purification method of 2-butyl-1,2-benzisothiazolin-3-one, wherein an acid is added to a mixture containing BBIT to make the BBIT form the salt, and the obtained BBIT salt is alkalized so as to obtain the high purity BBIT. According to the present invention, the synthesis method has advantages of easily available raw materials, mild reaction condition, high yield, low cost, low environmental pollution and convenient industrial production; and with the separation and purification method, the high purity target product can be obtained, and the method can be widely used for industrial production.
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Paragraph 0062-0065
(2017/09/08)
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- Potassium bromide catalyzed N[sbnd]S bond formation via oxidative dehydrogenation
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N-Substituted benzo[d]isothiazol-3(2H)-ones are a family of compounds with extremely important application. Recently, we have developed a new green pathway to synthesize these compounds via potassium bromide-catalyzed intramolecular oxidative dehydrogenative cyclization. This reaction has high functional group tolerance and affords excellent yield even in gram scale.
- Yu, Tian-Qun,Hou, Yong-Sheng,Jiang, Yi,Xu, Wen-Xuan,Shi, Tao,Wu, Xia,Zhang, Jin-Chao,He, Dian,Wang, Zhen
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supporting information
p. 2084 - 2087
(2017/05/10)
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- 2-butyl -1,2-benzisothiazolin-3-one synthesis method
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The invention discloses a synthesis method of 2-buyl-1,2-benzisothiazolin-3-one. The synthesis method comprises the following steps: taking an alcohol as a solvent and adding 1,2-benzisothiazolin-3-one into the alcohol; adding a base to the mixed alcohol solution; adding a certain amount of n-butyl sulfonate or n-butyl phosphate at a certain temperature, and finally, generating the 2-buyl-1,2-benzisothiazolin-3-one in 3-24 hours. The synthesis method of the 2-buyl-1,2-benzisothiazolin-3-one has the beneficial effects of low pollution, high reaction selectivity, high yield and extremely high economic benefit.
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Paragraph 0025
(2017/04/11)
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- An efficient approach to construct benzisothiazol-3(2: H)-ones via copper-catalyzed consecutive reaction of 2-halobenzamides and carbon disulfide
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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.
- Li, Ting,Yang, Lei,Ni, Kaidong,Shi, Zhenyu,Li, Fei,Chen, Dongyin
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p. 6297 - 6303
(2016/07/11)
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- Process for preparing benzisothiazolinones
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N-alkylated 1,2-benzisothiazolin-3-ones can be prepared in good yield and good selectivity by reaction of the lithium salt of 1,2-benzisothiazolin-3-one with an electrophilic alkylating agent.
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- PROCESS FOR PREPARING 1,2-BENZOISOTHIAZOLIN-3-ONES
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Sodium sulfide hydrate is at least partially dehydrated by heating with N-methyl 2-pyrrolidone. 2-Chlorobenzamide is added to the mixture which is heated further. The mixture is cooled and treated with aqueous hydrogen peroxide to give the sodium salt of 1,2-benzisothiazolin-3-one in good yield. Acidification if desired gives rise to the free 1,2-benzisothiazolin-3-one.
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Paragraph 0053
(2014/10/29)
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- Preparation of benzisothiazolones from 2-bromobenzamides and sulfur under copper catalysis conditions
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A convenient two-stage method has been developed for preparing benz[d]isothiazol-3(2H)-ones from 2-bromobenzamides and sulfur in a one-pot process under copper catalysis conditions. The method is suitable for the synthesis of N-aryl-, benzyl-, and alkyl-substituted benzisothiazolones. The yields of the benzisothiazolones depend on the nature of the starting amide and can reach 91%.
- Krasikova,Katkevics
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p. 1684 - 1690
(2013/07/04)
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- Concise approach to benzisothiazol-3(2 H)-one via copper-catalyzed tandem reaction of o -bromobenzamide and potassium thiocyanate in water
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A concise approach to various benzisothiazol-3(2H)-one derivatives has been developed by copper-catalyzed the reaction of o-bromobenzamide derivatives with potassium thiocyanate (KSCN) in water. The reaction proceeds via a tandem reaction with S-C bond and S-N bond formation.
- Wang, Fei,Chen, Chao,Deng, Geng,Xi, Chanjuan
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experimental part
p. 4148 - 4151
(2012/06/18)
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- Synthesis of 1,2-benzisothiazolin-3-ones by ring transformation of 1,3-benzoxathiin-4-one 1-oxides
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1,2-Benzisothiazolin-3-ones were synthesized from 1,3-benzoxathiin-4-one 1-oxides by means of a nonhazardous and inexpensive method. The 1,3-benzoxathiin-4-one 1-oxides were prepared by oxidation of 1,3-benzoxathiin-4-ones with hydrogen peroxide in the presence of a catalyst. Attack of amines on the carbonyl groups of the 1,3-benzoxathiin-4-one 1-oxides and subsequent elimination of carbonyl compounds likely produced sulfenic acids, which then underwent ring closure to afford the 1,2-benzisothiazolin-3-ones.
- Shimizu, Masao,Shimazaki, Teruaki,Yoshida, Tetsuya,Ando, Wataru,Konakahara, Takeo
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p. 3932 - 3936
(2012/07/14)
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- An efficient copper mediated synthetic methodology for benzo[d]isothiazol- 3(2H)-ones and related sulfur-nitrogen heterocycles
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A copper mediated sulfur-nitrogen coupling reaction for the synthesis of benzo[d]isothiazol-3(2H)-ones and related sulfur-nitrogen heterocycles has been presented, which requires 2-halo-arylamides, sulfur powder, 25-50 mol % of copper iodide/1,10-phenanthroline, and potassium carbonate as base.
- Bhakuni, Bhagat Singh,Balkrishna, Shah Jaimin,Kumar, Amit,Kumar, Sangit
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supporting information; experimental part
p. 1354 - 1357
(2012/04/10)
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- Crucial role of selenium in the virucidal activity of benzisoselenazol- 3(2h)-ones and related diselenides
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Various N-substituted benzisoselenazol-3(2H)-ones and their non-seleniumcontaining analogues have been synthesized and tested against selected viruses (HHV-1, EMCV and VSV) to determine the extent to which selenium plays a role in antiviral activity. The data presented here show that the presence of selenium is crucial for the antiviral properties of benzisoselenazol-3(2H)-ones since their isostructural analogues having different groups but lacking selenium either did not show any antiviral activity or their activity was substantially lower. The open-chain analogues of benzisoselenazol- 3(2H)-ones-diselenides also exhibited high antiviral activity while selenides and disulfides were completely inactive towards model viruses.
- Pietka-Ottlik, Magdalena,Potaczek, Piotr,Piasecki, Egbert,Mlochowski, Jacek
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experimental part
p. 8214 - 8228
(2011/03/19)
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- A practical synthesis of N-substituted 1,2-benzisothiazolin-3-ones from N,N′-disubstituted 2,2′-dithiodibenzamides
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A variety of N-substituted 1,2-benzisothiazolin-3-ones were easily synthesized from N,N′-disubstituted 2,2′-dithiodibenzamides in the presence of O-methylhydroxylamine hydrochloride. Derivatives with a primary, secondary, or tertiary alkyl group or an aryl group on the N-1 nitrogen of the 1,2-benzisothiazolin-3-one were obtained.
- Sano, Tomohumi,Takagi, Toshiyuki,Gama, Yasuo,Shibuya, Isao,Shimizu, Masao
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p. 1585 - 1588
(2007/10/03)
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- Methods of using spermicidal vaginal compositions comprising 1,2-benzisothiazole derivatives
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A spermicidal vaginal composition comprises a spermicidal-effective amount of a 1,2-benzisothiazole derivative having the general formula (I) STR1 wherein: X is either O or S; y is H; NO2 ; an halogen atom or an alkyl radical having from 1 to 4 carbon atoms; and R is H; a straight or branched alkyl or alkenyl radical having from 1 to 6 carbon atoms, optionally substituted by one or more hydroxyl, tertiary amino and alkoxyl groups; a cycloaliphatic radical having from 3 to 8 carbon atoms; an aryl radical optionally substituted by halogen atoms, alkyl or alkoxy radicals; an aralkyl radical optionally having the aromatic moiety substituted by halogen atoms, alkyl and alkoxyl radicals; or an acyl radical --COR' wherein R' is an alkyl group having from 1 to 4 carbon atoms or an aryl radical.
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