Synthesis Of Pyrrolo[1,2-a]quinoxaline Derivatives And Process Optimization Of 4-n-butyloxyphenol

Pyrrolo[1,2-a]quinoxaline,as an important nitrogenous fused-heterocycle compound,was widely presented as a key structural synthesis of various types of medicines,natural products,and organic functional materials.Pyrrolo[1,2-a]quinoxaline derivatives exhibit not only the properties and bioactivities in anti-inflammatories,antibacterials,antivirals and antiparasitics,but also have the applications in the optoelectronic materials for synthesis of dyes,fluorescent probes and electronic components.While p-alkoxyphenol,as an important organic synthesis intermediate,was widely applied in medicine,chemical and polymer industries.Among the p-alkoxyphenols,4-n-butyloxyphenol can not only help synthesis the monomer of novel liquid crystal polymer material PBPCS,but also work as an intermediate in the synthesis of pomacaine,a local anesthetic widely applied in clinical purposes.This dissertation was mainly focused on the synthesis of pyrrolo[1,2-a]quinoxaline derivatives and the industrial synthesis process optimization of the 4-n-butyloxyphenol.First,the development of free radical reaction to C-C and C-X(N,O,S,etc)bonds formation based on C-H bond activation was introduced.The resent representative reaction types were also summarized.Followed by the detailed introduction about the synthesis method of p-alkoxyphenol,the synthesis method and application of pyrrolo[1,2-a]quinoxaline,respectively.Furthermore,brief descriptions were given with typical implementations.Second,synthesis method of pyrrolo[1,2-a]quinoxaline derivatives via free radical strategy with using terminal methyl as a one-carbon synthon was developed.In conventional synthesis process,N-(2-aminophenyl)pyrrole was applied as a simple source for pyrrolo[1,2-a]quinoxaline derivatives synthesis,which was widely reported through the reaction with active substrates such as acids?alcohols and aldehyde ketones.However,while disadvantages of these methods were also claimed such as time consuming,high cost and strict reaction conditions.In this work a series of pyrrolo[1,2-a]quinoxaline and indolo[1,2-a]quinazolinederivatives were achived by free radical reaction with N-(2-aminophenyl)pyrrole and solvent DMF in the presence of Fe(?).Such reaction was not only suitable for common solvents of chain compounds such as N-methyl,O-methyl and S-methyl,but also exhibits tolerance towards amine and ether cyclic compounds to some extent.Furthermore,this method also performed applicable under mild reaction conditions,excellent functional group tolerance and wide substrate range.Therefore,this method provides a new method for the high yield synthesis of nitrogen-containing heterocycle and a novel idea for synthesis of complex pharmaceutical compounds.Third,the modification of massive synthesis process of 4-n-butyloxyphenol via Williamson method was investigated.In conventional synthesis process,hydroquinone worked as a cheap industrial source for the production,which reacted with alkylation reagent under catalytic condition to produce O-alkylation.Such method become a main route for recent industrial synthesis process.However,method applied alcohol compound and sulfonic ester as alkylation reagent and similar multistep methods were given up by industries since which cannot meet the requirement of organic synthesis process.Therefore,the current industrial process was mainly based on Williamson with hydroquinone and n-butylbromid.Despite some current reported method has better yield,but the yield was hard to reach beyond 50%without expensive or special designed equipment In order to overcome such issues,a modification of Williamson method was carried out with the optimized solvent,molar ratio and alkali modifications was carried out,giving a better synthesis method of 4-n-butyloxyphenol with low cost of source,simple operating and easy for massive production.This method has a substantial value of application in industrial massive production,providing more possibilities and making contributions to integrated production system of pomacaine industries.