Olefinic Bond Of Ammonia Addition Reaction Of Bromine And Its Applied Research

This thesis developed a serious of new systems of high regio-and stereoselective aminobromination of olefins. The general mechanism of aminobromination was proposed based on a large number of experiment results in this work. A new viewpoint was recommended in which the reaction how to work in aminobromination is according to substrate's structure strongly. For the applications of aminomromination to the olefins, the two new methods were developed. The first method is to synthesize aziridines via intramolecular cyclization of vicinal haloamine products. The corresponding aziridines were quantitative obtained catalyzed by urea. The second method is to synthesize N-protected α,β-dehydroamino derivatives via opening ring reaction of aziridines. The corresponding α,β-dehydroamino derivatives were obtained in excellent yield catalyzed by thiourea. The mechanism of the reaction was proposed. Nine chapters are included in this thesis. The first part (chapter one) includes a review of the aminohalogenation research progress and the determination of the subject for this thesis. The second part (chapter two to chapter eight) are the development of new systems of aminobromination reaction of olefins and their applications including to synthesize aziridines from vicinal haloamine products as well as synthesizing α,β-dehydroamino derivatives from aziridines. The third part (chapter nine) is a summary. The main contribution of this thesis is included in chapter two to chapter eight below:1Copper-Powder Catalyzed Aminobromination of α,β-Unsaturated Ketones (chapter2)Considering copper powder (Cu0) can be oxidized by NBS into Cu+or Cu2+, the idea of a Lewis acid produced in-situ from above oxidation to catalyze amonobromination of olefins was generated. Thus, a new method of aminobromination of α,β-unsaturated ketones has been developed in which the NBS and p-toluenesulfonamide (4-TsNH2) are as halogen and nitrogen sources and the copper powder is employed as catalyst to displace Cu(Ⅰ)-or Cu(Ⅱ)-containing compounds. The results showed that the reaction was carried out smoothly at room temperature to afford the desired aminobrominated products. The nearly quantitative products were obtained in most reactions under mild conditions without the protection of inert gaseous atmosphere. This method provides an easy process for preparation of vicinal aminohalo derivatives. The strong electron-donating substituents bearing benzene ring activate the double bond of α,β-unsaturated ketones remarkably to the addition reactions, whereas the strong electron-withdrawing substituents deactivate them, revealing that the addition reaction has an electrophilic feature. Regioselective of the reaction have been controlled in this method. The strong electron-donating substituents bearing4-position of benzene ring selectively afforded the a-bromo-β-amino adductive products and the strong electron-withdrawing substituents selectively afforded the a-amino-β-bromo adductive products.26Cases were investigated in this reaction which indicates that the new system is suitable for a wide scope.2Aluminium-Powder Catalyzed Aminobromination of α,β-Unsaturated Carbonyl Compounds and Simple Olefins(chapter3)Based on the copper powder can catalyze the aminobromination of α, β-unsaturated ketones, and in order to seek more efficient, low poisonous and less loaded catalysts for the regio-and stereoselective aminobromination of α,β-unsaturated carbonyl compounds and simple olefins, a systematic study was carried out via screening various elementary metals. Some elementary metal powders were also found to be suitable catalyst toward the aminobromination. Considering the lower toxicity and effectiveness of aluminium-powder, the new system of the aluminium powder-catalyzed high regio-and stereoselective aminobromination of α,β-unsaturated carbonyl compounds and simple olefins with the combination of TsNH2and NBS as halogen and nitrogen sources has been developed. The electron-rich and-deficient olefins shown significant differences in activity to the aminobromination reaction and gave the converse regioselectivity product. Based on a large number of experiment results, the possible mechanisms of aluminium-catlyzed aminobromination reaction for electron-deficient olefins including α,β-unsaturated carbonyl compounds and simple olefins were proposed. The proposed mechanisms involving process of bromonium and aziridinium intermediates not only could explains the anti-stereochemistry and the regioselectivity of the adductive products, but also explains well the remarkable difference in reactivity between the electron-rich olefin and electron-deficient olefin. The X-ray crystallographic study of3-bromo-4-(3.4.5-trimethoxyphenyl)-4-(p-toluenesulfonamido)butan-2-one showed clearly that the nitrogen atom was added to the β-carbon and the bromine atom was added to the a-carbon of the α,β-unsaturated ketones in trans relative stereochemistry.24Cases were investigated in this system which indicates that the new system has a wide scope suitable for the aminobromination of α,β-unsaturated ketones.Beside aluminium powder, the Cr,Mn,Zn,Mg,Sn,Sb and Pb et al elementary powders were also found to be good catalysts for the aminobromination of olefins.3Silicon Powder-Catalyzed Aminobromination of α,β-Unsaturated Carbonyl Compounds and Simple Olefins (chapter4)After the study of aminobromination reaction of olefins catalyzed by some metals powder successfully, a very important question was engraved on my mind:could or not nonmetal powders catalyze this reaction? Thereupon, our attention focused on the investigating the catalytic activity of11nonmetal elements powders in the aminobromination of olefins. Herein, the chalcone (1,3-diphenyl-propen-l-one) is as the model substrate, the reaction was carried out by stirring a mixture of catalyst, chalcone, NBS, and TsNH2in CH2Cl2at room temperature under the common conditions described above. The experiment result showed that the elemental silicon powder can be used as an efficient catalyst to the aminobromination reaction. This protocol has the advantages of applicability for a large scope of olefins (30cases) and high regio-and stereoselectivity with the NBS/TsNH2combination at ambient conditions. Additionally, silicon powder as catalyst has the advantage of avoiding any hazardous metals retained in the products. The relative nontoxicity, low cost, recyclability, and simpleness of silicon separation from reaction mixture make the methodology to be a useful tool for preparation of the vicinal aminobromo products, especially considering that the trace transition metal residues are highly regulated. More importantly. this may be the first example of using elemental silicon powder as catalyst in organic reactions.Beside silicon powder. the boron powder was found to be another efficient catalyst for the aminobromination of olefins. This result may be a promotion for the research of boron-organic chemistry.4(+)-Tartaric Acid-Catalyzed Aminobromination of α,β-Unsaturated Carbonyl Compounds and Simple Olefins(chapter5)Lewis acids were as efficient catalysts toward the aminohalogenation of olefins have been reported previously. Br(?)nsted acid (sulphuric acid) was also as catalyst has been reported recently. Considering the sulphuric acid has strong corrosivity,22kinds of organic acids have been screed for catalyzing aminobromination reaction of olefins. It was found that the tartaric acid was an efficient catalyst to this reaction. Thus, the new method of (+)-tartaric acid-catalyzed regio-and stereoselective aminobromination of olefins in CH2Cl2with p-toluenesulfonamido (TSNH2) and NBS as the nitrogen/bromine sources has been developed. This protocol offered an example of the small molecular organic acid-catalyzed methodology to synthesize civinal haloamino derivatives at the ambient temperature. The method is successfully applied to a wide range of α, β-unsaturated ketones. α,β-unsaturated esters and simple olefins (21cases). Among α, β-unsaturated carbonly compounds, higher regioselective isomers of a-bromo-β-amino products have been obtained when4-position of benzene ring bearing OCH3group. The other α,β-unsaturated carbonly compounds afforded correspouding converse isomers of a-amino-/?-bromo products. To the best of our knowledge.(+)-tartaric acid is a most convenient and practical organic small molecular catalyst to aminohalogenation so far.5K3PO4-Catalyzed Regiospecific Aminobromination of β-Nitrostyrene Derivatives with N-Bromoacetamide as Aminobrominating Reagent (chapter6)To expand the research scope of substrate for the aminobromination of olefins, an easy and efficient new method for the aminobromination reaction of β-nitrostyrene derivatives has been established. The method can conveniently and efficiently convert β-nitrostyrenes into vicinal haloamines at room temperature with N-bromoacetamide (NBA) in excellent yields (78-99%) and full regiospecificity products were obtained in CH2Cl2catalyzed by K3PO4. This methodology has advantages of low cost, nontoxicity, and elimination of the toxic issue associated with metal. The tendency indicates that the reaction is worked as a nucleophilic fashion due to the more electron-deficient is in the double bond of substrate, the more reactivity behave in the reaction. A possible mechanism involving conjugate addition was proposed and it explains well the reactivity of substrates and the regiochemistry of products.6Solvent-Free Grind:a Rapid and Simple Method for Quantitative Synthesis Aziridine from Aminobrominated Derivatives of Various Olefins (chapter7)Aziridination is an important synthetic transformation. Aziridines are found broad in the Pharmaceuticals and agrochemicals as electrophiles and as synthetic intermediates. Although the formation of aziridines from the addition of thermally or photochemically generated nitrenes to olefins is a well-known reaction, its utility is limited due to low yields and competing hydrogen abstraction and insertion reactions. In the preparation of aziridines, the metal catalyst is necessary in previously aziridination methods. In this chapter, a new method of urea-catalyzed aziridination of vicinal haloamino compounds with unexpectedly high efficiency has been developed. This protocol is a very easy and eco-friendly procedure for the aziridination of aminohalogenated derivatives of olefins by simply grinding the solid mixture of the substrate, K2CO3and catalytic amount of urea at room temperature in air. The reaction proceeded completely and cleanly to give aziridines in quantitative yields, and thus this method provides a "real" green protocol for preparation of aziridines from a large scope of aminohalogenated derivatives of simple and electron-deficient conjugated olefins. Compared with the standard procedures, this method offers many essential advantages such as quantitative yields, mild conditions, short reaction times, easy work-up and elimination of the toxicity issues related to metal catalysts.7Thiourea-Catalyzed Synthesis of α,β-Dehydroamino Derivatives from Aziridines (chapter8)The functionalized enamines have long served as the useful building blocks in the synthesis of a variety of importance different structure compounds in the biological chemisty and the pharmaceutical chemistry. As a member of this family, a-ketoenamines (also referred to as α,β-dehydroamino derivatives) occur frequently as a unit in natural products and biologically active compounds. This unit also plays an important role in organic synthesis. Not only this is the application of organic synthesis in the electrophilic and the nucleophilic chemistry, but also is the application in the photochemistry and the electrocyclic reactions, especially for the synthesis of the heterocyclic compounds. As one of an important application of aziridines, how to transform aziridines into corresponding α,β-dehydroamino derivatives in high yields is a topic of the organic synthesis so far. Thus, aziridine was converted into corresponding α,β-dehydroamino derivatives has been studied in this work and an easy and efficient new method has been established. The experiment result indicated that various aziridines can be transformed into corresponding α,β-dehydroamino derivatives in nearly quantitative yield catalyzed by K2CO3/NH2CSNH2in a mixing solvent (CH2Cl2:DMF=1:1(v/v)) at room temperature(16cases,97%-99%yield). This protocol has many advantages such as handling easily, high selectivity, high yield. And, the reaction can be catalyzed by an available, stable and economical thiourea. This method affords an efficient process for preparing various α,β-dehydroamino derivatives. The reaction mechanism has been discussed in this thesis.