2-alkylation Of Quinoline N-oxide And The Synthesis Of ?-hydroxy Sulfones

Quinoline and its derivatives are a class of very important organic compounds,it has important applications in organic chemistry,natural products and pharmaceutical chemistry and other fields.Quinoline and its derivatives have a variety of biological and pharmaceutical activity,Such as anti-bacterial,anti-inflammatory,antihypertensive,anti-allergy,antidepressant,anti-tumor,anti-cancer and anti-HIV.However,quinoline compounds are easily oxidized to 2-hydroxy quinoline in the human body,which greatly reduce or even lose its drug activity and biological activity,In order to prevent the occurrence of such an oxidation process,it is often carried out by modifying the quinoline 2-position.In the past,to build carbon-heteroatom bond to modify quinoline in its 2-position is the main method of modification.The method of modifying by carbon-carbon bond in the 2-position of quinolines is limited in number,what's more,it's concentrated in the modification by2-arylation of quinolines,and few methods are used to modify the quinoline by synthesis 2-alkyl quinoline.A novel scheme for alkylation of quinoline by cross-de-hydrogenation coupling reaction with extremely high atomic economy is proposed in this paper,It has the advantages of green,cheap and practical.This way is a green,cheap and practical scheme to synthesize 2-alkyl quinolines.To put the quinoline N-oxides,the active methylene reagent,the H-phosphite,the carbon tetrachloride and the potassium carbonate are placed in the DMF solution,stir for three hours in one-pot at room temperature in the air,then obtain the target compound after extraction and separation.The advantage of this method is that the raw materials are cheap and easy to obtain,the reaction is quick,the condition is mild,and the regional selectivity is highly.?-hydroxy sulfone compounds are a common organic synthesis intermediates,in the field of asymmetric synthesis has a wide range of applications.What's more,?-hydroxy sulfone compounds also have drug activity such as anti-cancer,anti-fungal.The following four methods are the traditional synthesis of ?-hydroxy sulfone compounds:(i)The nucleophilic reaction of sodium sulfite with epoxy derivative,(ii)The reduction reaction of ?-keto sulfones,(iii)The hydroxylation reaction of ?,?-unsaturated sulfones,(iv)The addition reaction of sulfonic acid(salt),sulfonyl derivatives with alkene.In this paper,we use tert-butyl sulfenamide and styrene-based compounds as source to synthesize the ?-hydroxy sulfone compounds at 40 degrees Celsius conditions in one-pot in air,which provides a new idea for the synthesis of ?-hydroxysulfone compounds.Compared with the previous method,the advantage of this reaction is Cheaper reagents,more moderate condition and simpler steps.The main research contents are as follows:(?)A New Method for 2-Alkylation of Quinoline1.The properties,synthesis methods and actual application of quinolines and its derivatives are summarized.2.The quinoline N-oxides and ethyl acetoacetate was used as model reaction to optimize the reaction conditions.The kinds and amount of phosphorus reagent,the kinds and amount of bases,the amount of carbon tetrachloride,reaction solvents,ratio of raw materials,time and temperature are screened.The obtained optimalconditions are: 0.4 mmol of quinoline N-oxide,0.4 mmol of acetoacetic ester,0.8mmol of diethyl H-phosphonate,0.8 mmol of K2CO3,and 0.5 m L of carbon tetrachloride in 1.0 m L DMF at room temperature for 3 h.3.Under the optimized reaction conditions,the reaction scope was investigated via the use of quinoline N-oxides with different substituents and active methylene compounds with different electron-donating groups.A total of 23 target compounds were obtained and their structures were characterized by ~1H,13 C NMR and HR MS.4.Explore the mechanism of the reaction using free radical blocking and so on.(?)A New Method for Synthesis of ? – Hydroxysulfone1.The reaction was optimized,including time,temperature,substrate ratio,and the type and amount of catalyst,phosphorus reagent,acid and solvent.The results were as follows: 0.5 mmol of styrene,0.5 mmol of tert-butylsulfenamide,20 mmol%of copper sulfate pentahydrate,0.75 mmol of phosphorous acid and 1.0 mmol of trifluoroacetic acid,and the reaction was carried out at 40 o C for 12 h without solvent.2.Under the optimized reaction conditions,the reaction scope was investigated via the use of styrene compounds with different substituents and tert-butylsulfenamide.A total of 9 target compounds were obtained and their structures were characterized by ~1H,13 C NMR and HR MS.3.Explore the reaction mechanism.