Investigation On Nitrogen Dioxide-Catalyzed Aerobic Oxidative Thiocyanation Of Arenes

The thiocyanation of arenes is an important and fundamental transformation in modern organic synthesis because the resulting products is frequently used to synthetize a wide range of chemicals,e.g.sulfur-containing compounds and N-heterocyclic compounds.As a result,considerable attention is attracted by the present reaction where(SCN)2,and SCN+ are,at the early stage,used as thiocyanation reagent.However,(SCN)2 is unstable and toxic gas.By comparison,the compounds with a pronounced SCN+ character(e.g.N-thiocyanatosuccinimide)are more expensive,and their use easily resulting in large amount of organic wastes.So the inexpensive and readily available thiocyanate salts with SCN-are more attractive alternative.However,the SCNanion as a nucleophile is unreactive towards the aromatic rings.According to the law of charge conservation,the presence of an oxidizing reagent is necessary to in-situ oxidate the SCN-or aromatic rings to the reactive species,and this kind of reaction is also known as oxidative thiocyanation where the effective oxidants mainly involve hydrogen peroxide,potassium persulfate,ammonium metavanadate and iodine pentoxide.Compared with the mentioned above oxidants,the inexpensive and environmentally friendly oxygen gas,especially air,is more attractive.Surprisingly,only two examples of the oxidative thiocyanation of arenes have been reported in previous literatures where the substrates are limited to indoles and imidazoheterocycles,and the used catalysts is rose bengal and eosin Y.In the present thesis,an effective method for the thiocyanation of other substrates is developed using air as the terminal oxidant under the catalysis of nitrogen dioxide as the unique catalyst,which opens an avenue to synthesize aryl thiocyanates.The main research contents and conclusion are as follows.(1)Oxidative thiocyanation of arenes with amine groups was carried out using nitrogen dioxide as the catalyst,and oxygen as the terminal oxidant.Firstly,thiocyanation of N,N-diethylaniline was used as a model reaction to investigate the influence of various conditions on the reaction.The presence of a br?nsted acid remarkably facilitated the aerobic oxidative reactions,and trifluoroacetic acid was optimal among screened acids.In addition,the reaction was highly dependent on the reaction temperature.Complete conversion and high yield was observed in the range from 0 to 15oC.When the reaction temperature was increased to more than 20oC,both the conversion of substrate and the yield of the targeted product decreased significantly.It is difficult to understand why the conversion of the substrate become lower withincreasing the reaction temperature,which is possibly due to the deactivation of the catalytic species.Based on the results above,the optimal reaction conditions are summarized as follows: 1.3 equiv.NH4 SCN,9.2 mol% NO2,0.2 mL CF3 COOH,2 mL acetonitrile,15oC,3 h and 1atm air.Next,the reactions of different arylamines were investigated under the optimal reaction conditions,and the results showed that the reaction proceeded smoothly in the case of tertiary amine,while the substrates with primary and secondary amine groups are less reactive,which is possibly due to that these amine groups have stronger alkalinity and can destroy the catalytic species.In addition,electronic property and steric hindrance have varying degrees of influence on the thiocyanation reaction.(2)Oxidative thiocyanation of alkoxy group-substituted arenes and heterocyclic arenes was carried out using nitrogen dioxide as the catalyst,and oxygen as the terminal oxidant.Based on the optimal reaction conditions relative to the arylamine,the reaction of anisole and 1-methoxynaphthalene was investigated.The experimental results showed that the nitrogen dioxide was effective as the catalyst for this substrate,but anisole was unreactive.Various representative alkoxyaromatics and heterocyclic compounds were test to explore the scope and generality of the present reaction,and the results revealed that alkoxynaphthalenes,aryloxynaphthalenes,1,2,3-trimethoxybenzene,thiophene were smoothly thiocyanated.Our method was applicable to the selective functionalization of one aromatic ring if the substrate contains two or more aromatic rings,which prompted us to perform several competition reactions between two aromatic substrates.The experimental results suggested that the thiocyanation selectively occurred at the amine goup-substituted substrate in the presence of the electron donating or withdrawing group-substituted substrate.When anisole encountered naphthalene ring with a tertiary amine group,the thiocyanation of both two aromatic rings occured,and larger amount of thiocyanation product from naphthalene ring was observed.(3)Subsequently,several experiments were performed to clarify the oxidant and the real catalytic species.The results reveal that the residual oxygen in the reaction tube plays the role of the oxidant,and NO~+ seems to be one of the real catalytic species.Two kinds of possible mechanistic pathways for the oxidative thiocyanation have been proposed in the previous literatures.One starts with the reaction between the oxidativespecies and the aromatic rings to give the aromatic radical cations or a π-complex.The other starts with the oxidation of SCN to(SCN)2,SCN radical,or a reactive species with a pronounced SCN+ character.We performed several control experiments in which the well-known radical scavenger TEMPO was added to the reaction system.The presence of TEMPO led to a dramatic decrease in the yields of the thiocyanation products,which reveals that the reaction proceeds through either the aromatic radical or the SCN radical pathway.We believe that one of the most probable mechanism pathways involves the oxidation of the aromatic ring by NO~+ because NO~+ species possess the ability to oxidize various aromatic rings to cation radicals.The catalytic cycle starts with the reaction between the aromatic ring and NO~+to give the aromatic radical cation and NO.The latter is oxidized by O2 to regenerate the catalytically active NO~+.The resulting aromatic radical cation reacts with SCN to form a neutral radical intermediate,followed by electron transfer and deprotonation to give the targeted aryl thiocyanate product.