- Development of a large-scale asymmetric process for tert-butanesulfinamide
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Process development for a scalable and green synthesis of chiral tert-butanesulfinamide (TBSA) on a multikilogram scale is reported. The process is based on the identification of a chiral sulfinyl transfer agent, benzo[1,3]oxathiozin-2-one, that contains active and differentiated S?N and S?O bonds, allowing the synthesis to proceed under mild reaction conditions. This method is practical and overcomes the disadvantages of earlier methods deploying harsh reaction conditions and hazardous and toxic reagents.
- DeCroos, Philomen,Han, Zhengxu S.,Sidhu, Kanwar,Lorenz, Jon,Nummy, Larry,Byrne, Denis,Qu, Bo,Xu, Yibo,Wu, Ling,Lee, Heewon,Roschangar, Frank,Song, Jinhua J.,Senanayake, Chris H.
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Read Online
- Method of synthesizing enantiomerically pure tert-butanesulfinamide
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The invention discloses a method of synthesizing enantiomerically pure tert-butanesulfinamide. The method comprises the following steps of using tert-butyl disulfide and hydrogen peroxide for selective oxidation, then performing reaction on a product and an acylation reagent to obtain tert-butylsulfinyl chloride or tert-butylsulfinyl bromide, then performing reaction on the tert-butylsulfinyl chloride or the tert-butylsulfinyl bromide and hydrazine hydrate to obtain tert-butylsulfinyl hydrazine, then performing reaction on the tert-butylsulfinyl hydrazine and a DTTA resolving agent for resolution and dissociation, and performing zinc/acetic acid pyrolysis to obtain the enantiomerically pure tert-butanesulfinamide. The method provided by the invention is simple, convenient and stable in technological operation and high in yield, is environmentally friendly, is cheap and available in raw materials compared with the prior art, lowers the production cost of the existing enantiomerically pure tert-butanesulfinamide and is beneficial to industrialized mass production.
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Paragraph 0060
(2018/09/11)
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- Method for preparing enantiomer pure methylpropane-2-sulfinamide
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The invention discloses a method for preparing enantiomer pure methylpropane-2-sulfinamide. The method comprises the following steps: performing selective oxidation on tertiary butyl dithioether and hydrogen peroxide; adding an acylation reagent so as to obtain tertiary butyl sulfonyl chloride or tertiary butyl thionyl bromide; adding hydrazine hydrate so as to obtain tertiary butyl thionyl hydrazine; further performing resolving dissociation with a tartaric acid resolving agent; performing cracking with zinc acetate, thereby obtaining the enantiomer pure methylpropane-2-sulfinamide. The method is simple and stable in process operation, high in yield and good in environment protection, and compared with a conventional process, the method is low in raw material price, easy in raw material obtaining, capable of reducing the production cost of conventional enantiomer pure methylpropane-2-sulfinamide, and beneficial to industrial on-scale production.
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Paragraph 0015; 0058; 0060
(2018/09/29)
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- Method for preparing pure enantio-methylpropane-2-sulfinamide
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The invention discloses a method for preparing pure enantio-methylpropane-2-sulfinamide. The method comprises the following steps: carrying out selective oxidation on di-tert-butyl disulfide and hydrogen peroxide, reacting with an acylation reagent so as to obtain tert-butylsulfinyl chloride and tertiary butyl sulfonyl bromide, further reacting with hydrazine hydrate so as to obtain tertiary butylhydrazide, further carrying out resolution and separation with a DBTA resolving agent, and carrying out cracking with zinc acetate, thereby obtaining the pure enantio-methylpropane-2-sulfinamide. Themethod is simple, convenient and stable in process operation, high in yield and good in environment protection, and compared with a conventional process, the method is cheap and easy in raw materialobtaining, low in production cost of pure enantio-methylpropane-2-sulfinamide, and beneficial to industrial on-scale production.
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Paragraph 0015; 0041; 0058; 0060
(2018/10/19)
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- Process for synthesizing chiral tert-butanesulfinyl amide
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The invention discloses a process for synthesizing chiral tert-butanesulfinyl amide. The process includes carrying out reaction on tert-butyl mercaptan and iodine/hydrogen peroxide acetone to generate di-tert-butyl disulfide; oxidizing hydrogen peroxide under the catalytic effect of vanadium to generate chiral tert-butyl sulfenyl tert-butyl mercaptide; carrying out one-pot reaction on the chiral tert-butyl sulfenyl tert-butyl mercaptide and lithium reagents/liquid ammonia in the presence of alkyl chloride to obtain the tert-butanesulfinyl amide. Compared with existing processes, the process has the advantages that the smoothness of the process can be enhanced, the usage of the liquid ammonia can be reduced to a great extent, and the operational efficiency can be improved.
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Paragraph 0018; 0019
(2017/08/28)
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- Design and synthesis of chiral oxathiozinone scaffolds: Efficient synthesis of hindered enantiopure sulfinamides and sulfinyl ketimines
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Is that S-O? The title scaffolds have a highly active and properly differentiated S-O bond for the efficient synthesis of enantiopure sulfinamides. The method is practical, green, and has the potential to provide an economical commercial process for the synthesis of bulky sulfinamides. Copyright
- Han, Zhengxu S.,Herbage, Melissa A.,Mangunuru, Hari P. R.,Xu, Yibo,Zhang, Li,Reeves, Jonathan T.,Sieber, Joshua D.,Li, Zhibin,Decroos, Philomen,Zhang, Yongda,Li, Guisheng,Li, Ning,Ma, Shengli,Grinberg, Nelu,Wang, Xiaojun,Goyal, Navneet,Krishnamurthy, Dhileep,Lu, Bruce,Song, Jinhua J.,Wang, Guijun,Senanayake, Chris H.
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supporting information
p. 6713 - 6717
(2013/07/26)
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- The fate of the tert-butylsulfinyl auxiliary after acid-promoted cleavage-a method for recycling t-BuSONH2
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Ellman's chiral auxiliary is converted into tert-butylsulfinyl chloride on sulfinamide deprotection with HCl and can be recovered in high yield upon treatment with ammonia. The enantiopure auxiliary can be obtained by trapping the sulfinyl chloride with a chiral alcohol followed by treatment of the resulting sulfinate ester with LiNH2.
- Aggarwal, Varinder K.,Barbero, Nekane,McGarrigle, Eoghan M.,Mickle, Greg,Navas, Raquel,Suárez, José Ramón,Unthank, Matthew G.,Yar, Muhammad
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supporting information; experimental part
p. 3482 - 3484
(2009/09/28)
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- Practical and highly stereoselective technology for preparation of enantiopure sulfoxides and sulfinamides utilizing activated and functionally differentiated N-sulfonyl-1,2,3-oxathiazolidine-2-oxide derivatives
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A simple, general, and practical technology to prepare enantiopure 1,2,3-oxathiazolidine-2-oxide derivatives using chiral aryl N-sulfonyl aminoalcohol derivatives and thionyl chloride is reported. The versatility of these novel chiral building blocks (MIOO and TMPOO), was exemplified by the expedient production of a variety of unique chiral sulfoxides and valuable chiral sulfinamides in excellent yields and enantiopurities.
- Han, Zhengxu,Krishnamurthy, Dhileepkumar,Grover, Paul,Fang, Q. Kevin,Su, Xiping,Wilkinson, H. Scott,Lu, Zhi-Hui,Magiera, Daniel,Senanayake, Chris H.
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p. 6386 - 6408
(2007/10/03)
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- Improved synthesis of tert-butanesulfinamide suitable for large-scale production
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(Matrix presented) An improved synthesis of tert-butanesulfinamide that overcomes the scalability problems of the previous syntheses is described. The key step is the catalytic asymmetric oxidation of the inexpensive di-tert-butyl disulfide starting material. The new homogeneous reaction conditions utilize an inexpensive chiral ligand prepared in a single step from commercially available cis-1-amino-indan-2-ol. The reaction is performed at a 2.3 M concentration in the practical solvent acetone and can readily be run on a kilogram scale.
- Weix, Daniel J.,Ellman, Jonathan A.
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p. 1317 - 1320
(2007/10/03)
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- Properly designed modular asymmetric synthesis for enantiopure sulfinamide auxiliaries from N-sulfonyl-1,2,3-oxathiazolidine-2-oxide agents
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Simple and practical asymmetric synthesis of functionally differentiated aminoindanol based endo-N-sulfonyl 1,2,3-oxathiazolidine-2-oxide as sulfinyl transfer agents are developed. The importance of these new and unique sulfinyl transfer reagents are exemplified by the expedient production of several sulfinamide ligands, including either enantiomer of (R)-tert-butanesulfinamide in excellent yields and enantiopurities. Copyright
- Han, Zhengxu,Krishnamurthy, Dhileepkumar,Grover, Paul,Fang, Q. Kevin,Senanayake, Chris H.
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p. 7880 - 7881
(2007/10/03)
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