Applications Of α-Oxo Ketene Dithioacetals As Odorless Thiol Equivalents In Organic Synthesis

It is well-known that thiols are kind of versatile reagent and have been widely utilized in organic synthesis. However, commonly used thiols, such as methanethiol, ethanethiol and benzyl mercaptan, having toxicity and a foul smell, can lead to environmental and safety problems. To develop green chemistry, we study systematically the application of commercially available, odorless and stable α-oxo ketene dithioacetals substituting for thiols in organic synthesis. As nonthiolic odorless thiol equivalents, their thioacetalization reaction, thia-Michael addition and the nucleophilic substitution reaction were carried out successfully under mild reaction conditions, which indicated that the application of a-oxo ketene dithioacetals in organic synthesis had been further developed, and which is propitious to environment and human due to escaping the use of toxic and foul smell thiols.1. Firstly, thioacetalization reaction of 3-(1, 3-dithian-2-ylidene)-pentane-2, 4- dione la and 1-(1, 3-dithian-2-ylidene) propan-2-one 4a as equivalent of propane-1, 3-dithiol had been succefully carried out in MeCOCl-MeOH. Compound 4a was chosen as optimal equivelent of propane-1, 3-dithiol on the basis of the reaction activity in thioacetalization reaction. Then the analogs of 4a: 1-(1, 3-dithiolan-2-ylidene) propan-2-one 4b, 4,4-bis (ethylthio/benzylthio) but-3-en-2-one 4c and 4d were investigated as equivalents of ethane-1, 2-dithiol, ethanethiol and benzyl mercaptan in thioacetalization reaction, respectively, and the thioacetalization products were obtained in high yield.2. 4 in MeCOCl-MeOH and 2-[bis(alkylthio)menthylene]-3-oxo-vV-o-tolylbutan amide 8a-e as odorless thiol equivalents in NaOH-EtOH had been studied in thia-Michael addition reaction at room temperature, respectively. 4 and 8 underwent facile conjugate addition to a, (3-unsaturated carbonyl compounds affording corresponding P-keto sulfides in very high yield in respective reaction system. Meanwhile, 3-oxo-iV-o-tolylbutanamide 7, the precursor of compounds 8, could be recovered from thia-Michael addition reaction in good yield.3. 8 reacted with a series of epoxides to afford corresponding sulfides at room temperature in NaOH-EtOH. The experimental results revealed that the addition reaction between 8 and asymmetrical oxiranes, for example 2-phenyloxirane and 2-methyloxirane, proceeded in a highly regioselective manner, and thiolate anoins generated preferred to attack on the less-hindered carbon of the epoxides. However, when reacting with calchone oxide, only 2-(alkylthiol)-l-phenylethanones deriving from the retroaldol reaction were isolated in high yield. In addition, the nucleophilic substitution reactions of 8 as thiol equivalents with 2-bromo-1-arylethanones, which are sensitive to alkali, and alkylogens were successfully carried out under above conditions. Moreover, 3-oxo-iV-o-tolylbutanamide 7, the precursor of compounds 8, could be recovered from these reactions in good yield, too.