| Taurine and its derivatives are a series of naturally occurring amino acids, which play an indispensible role in the life body. As a nutrient, it widely used in food, drink, medicine and so on. In China, taurine has a very broad market space because their per capita consumption is greatly lower than that in developed countries. With the rapid development of pharmaceutical chemistry, the biological activities of various substituted taurines and their derivatives had been developed by the biochemical scientists. Therefore, synthesis of various substituted taurines was attracted by the more and more organic synthetic scientists. Herein, based on the reported methods, we have developed three kinds of synthetic methods of taurine and substituted taurines, hoping to fill up some vacancies in the preparation of substituted taurines.1. Synthesis of2,2-dialkyl or aromatic1,1-disubstituted taurines from2,2-disubstituted aziridines and sodium sulfide or bisulfide.2,2-Dialkylaziridines were specifically attacked on their less substituted carbon atoms with sodium bisulfite, affording2,2-substituted taurines; while2,2-disubstituted aziridines with either one or two aryl substituent(s) were attacked specifically on their more substituted carbon atoms with the same nucleophile, giving rise to aromatic1,1-substituted taurines. Sodium sulfite attacked the less substituted carbon atoms of all aziridines specifically to afford2,2-disubstituted taurines. The regioselectivity is governed by the nucleophile and the balance between the steric hindrance and the electronic effect. The current method provides an alternative route to synthesis of2,2-dialkyltaurines and aromatic1,1-disubstituted taurines.2. Salt-free synthesis of versatile substituted taurines by oxidation of thiazolidine-2-thiones.Taurine and structurally diverse substituted taurines have been synthesized efficiently via oxidation of thiazolidine-2-thiones, which were prepared conveniently from the corresponding amino alcohols or aziridines. Compared with the previous synthetic method, the current route can be used for the synthesis of1-substituted,2-substituted,2,2-disubstituted, and N-substituted taurines, including linear, cyclic, and optically active taurines. Furthermore, this method is an inexpensive, versatile, and salt-free procedure for synthesis of highly pure and diverse taurines in both industrial large-scale production and laboratorial preparation.3. Salt-free synthesis of1,2-disubstituted taurines from the α,β-disubstituted nitroolefins.Nitroalkylthioacetates, generated from nitroolefins and thioacetic acid, could be oxidized by peroxyformic acid and then reduced by hydrogen on palladium on carbon powder to afford the corresponding substituted taurines, especially the1,2-disubstituted taurines. In the Michael addition of nitroolefins and thioacetic acid, we separated the diastereoisomers by recrystallization and column chromatograph, identified the structures by the Karplus equation analysis in lH NMR, computational analysis, and XRD of single crystals, and deduced the diasteromeric ratio by the Cram Rule I. The method also could be applied in the preparation of1-,2-substituted and1,1-disubstituted taurines.In addition, we also systemically studied the synthesis of different intermediates and their formation mechanisms. Chlorosulfonic acid was widely used in the preparation of N-H aziridines and thiazolidine-2-thiones. In the synthesis of aziridine, when chlorosulfonic acid used, the yield of2-aryl aziridines was dramatically improved. The2,2-diaryl substituted aziridines, which could not be synthesized by the conventional Wenker method, were generated by using chlorosulfonic acid. Three methods were provided to prepare the versatile thiazolidine-2-thiones. While in the improved method via aminoalcohol hydrogen sulfates as intermediates, the yield of thiazolidine-2-thiones also increased obviously. Furthermore,5,5-disubstituted thiazolidine-2-thiones were also been separated in the reaction, which was proved by the Thorpe-Ingold effect. |
PDF Full Text Request