Catalyst-free Synthesis Of Quinoxaline And The Condensation Reaction Of Tert-butanesulfinamide

1. Catalyst-free synthesis of quinoxalinesQuinoxalines is a class of aromatic heterocyclic compounds. Quinoxalines andits derivatives play a very important role in agriculture, industry, pharmaceuticals andanimal husbandry. For example, a new herbicide quinoxaline (R0017-3664) can beused to control of weeds in broadleaved crops TianZhonghe; one kind of quinoxalinederivatives polyimide PMR (Polymerization of Monomer Reactants) can be used tosynthetic polymers; quinoxaline derivatives can be used in the manufacture of OLED(Organic Light Emitting Diode); Quinomycins and Triostins are the efficacy ofanti-carcinogenic&anti-neoplatic; Carbadox can be used for antibacterial and growthpromoting additives. Therefore, study of thesynthesis of quinoxalines has veryimportant significance.As early as one hundred years ago, there exist synthetic studies of quinoxalines.In recent years, studies ofthe synthesis ofquinoxalinesare also active. Literatures havereported many methods of synthesis of quinoxalines, which is mainly made ofo-phenylendiamine, such as o-phenylendiamine with α-hydroxyketone,o-phenylendiamine with α-halogenateketones, o-phenylendiamine with ketonecompounds, o-phenylendiamine with diols, o-phenylendiamine with epoxycompounds, o-phenylendiamine with the benzaldehydes. Although these methods canefficiently synthesize quinoxalines, but these methods also have some defects, such astoxic catalyst, high cost, tedious reaction steps, difficult purification. So, to explore anew synthetic method (such as finding a suitable solvent or catalyst) of quinoxalineshas important research significance.We choosed o-phenylendiamine and α-bromoacetophenone as raw materal forsynthesis quinoxaline compounds. The effects of factors, such as the type and amountof catalyst, reaction temperature, reaction time, the type and amount of base, solventand other factors were investigated. We finally reached the best rection system,o-phenylendiamine: alpha-bromoacetophenone: base=1:1:1.2, DMSO as solvent,under air at120℃for24hours in an open test tube. The reaction yields reached up to99%. The system is not only easy purification, but also friendly to environment. Under the optimized conditons, we examined o-phenylendiamine with variousα-haloketones, respectively, such as2-bromo-4′-methoxyacetophenone,2-bromo-4-phenylacetophenone,2,4’-dibromoacetophenone. We also examined the reaction ofα-bromoacetophenone with o-phenylendiamine and it’s derivatives, such as1,2-diamino-4,5-dimethylbenzene,4-methoxy-o-phenylenediamine. Under theoptimized conditions, high yields are obtained. According to the results, this protocolis suitable for a wide scope of the substrates.2The condensation reaction of tert-butanesufinamideN-aryl-tert-butanesulfinamides are very important nitrogen-containing organiccompounds. It has important biological activities, medicinal value and commercialvalue. For example, N-aryl-tert-butanesulfinamides can be used to synthesizeneurokininreceptoragonists (NK1) and antibiotics.The synthesis of N-aryl-tert-butanesulfinamides has few reports, and the reportedsynthesis procedures are multifarious, need expensive or toxic catalyst.Zhao YunHui uses alicylicaldehyde and tert-butanesulfinamide under thecondition of microwave heating synthesis N–aryl-tert-butanesulfinamide, although theyield is ideal, but it is difficult to purify, and the universality of the reaction system isnot good.Sun Xiaofei, a former teamer of our group, studied the C-N coupling reaction ofaryl halides and tert-butanesulfinamide using expensive palladium catalyst and a toxicorganic phosphorus ligand. We tried to use optical pure, cheap accessibletert-butanesulfinamide with anilines to synthesize N-aryl-tert-butanesulfinamides.We investigated the condensation reaction of tert-butanesulfinamide, chooseanilines and tert-butanesulfinamide as reactants. The effecting factors, such as the typeand amount of catalysts, solvent, reaction temperature, reaction time were investigated.We finally reached the optimalconditions. The best reaction conditions are potassiumphosphate monobasic (15mol%),1,4-dioxane as solvent, at90℃for36hours in anargon protecting test tube. Under the optimized conditions, we examined the reactionsof tert-butanesulfinamide with o-toluidine, m-toluidine, p-toluidine, m-chloroaniline,p-chloroaniline and4-bromoanilines. We found the generality of the reaction systemwas not good, and we only obtained racemic N-aryl-tert-butanesulfinamides.We also investigated theself-condensation of tert-butanesulfinamide andpara-toluenesulfonamide. To our surprise, even in very mild condition,tert-butanesulfinamide could carry out self-condensation. The best rection system is: 1,4-dioxane as solvent, at110℃for15hours in an test tubeunderargon. The reactionyield is up to95.8%.