Studies On The Organic Synthesis Reactions In Which Inexpensive Metal Activated Alcohols As Alkylating Agents

In organic chemistry, the C-C bond formation is most fundamental and pivotal forsynthesizing more complex molecular structures; the alkylation reaction is one of routinereactions for the formation of the C-C bond. However, the traditional alkylating agents (i.e.alkyl halide, alkyl sulfonate, alkyl sulfate, etc) inevitably bring a lot of salt byproducts, inwhich some are even toxic and hazardous; so many drawbacks exist in the view of atomeconomy and environmental protection. Therefore, activate alcohol compounds, especiallyprimary alcohols, are explored as alkylating agents of organic synthesis reactions.However, nowadays, the alkylation reaction with primary alcohols as alkylating agentsstill mainly uses the rare and expensive transition metal catalysts including Ru, Rh, Ir, Pd, etal, and some shortages exist:1) the catalysts is specially synthesized, rather than commercial;2) a lot of hydrogen donor (acceptor) and complex N, P ligands are needed;3) thestoichiometric alkali is needed and has serious environmental influences. Therefore, theexploitation of cheap metals as catalysts has been a great challenge facing by the scientists.In this study, on the basis of the preliminary work of our lab, we not only studied deeply onthe substrate applicability of β-alkylation of secondary alcohols using iron activated primaryalcohols as alkylating agents, but also have a preliminary investigation for the reactionmechanism. Moreover, we made a preliminary exploration for the possibility of β-oxidativealkylation of secondary alcohols using cheap metal (especially iron catalyst) activatedprimary alcohols. These works not only deepen our understanding and knowledge of ironcatalyst, but also extend the application of iron catalyst in organic synthesis reactions.Firstly, on the basis of our lab’s previous study on direct β-alkylation of secondaryalcohols, we attempt further study on the substrate applicability to1-phenyl alcohols, benzylalcohols, aliphatic primary alcohols, aliphatic secondary alcohols and heterocyclic substratesand obtain seven kinds of senior alcohols compounds with yield at54%~95%. This studyfirstly applies iron catalysts to the direct β-alkylation of secondary alcohols with activatedalcohols as alkylating agents, and has explored new catalyst systems and enriched the kindsof metal catalysts. This catalyst is cheap and easy to get and supplies new choices for findingthe alternatives of commonly used noble metal catalysts.Secondly, we attempt to make preliminary discussion to the reaction mechanism of direct β-alkylation of secondary alcohols. At the period of the parameter optimization forsubstrate applicability study, we have detected many intermediate products, for example:acetophenone, etc. For obtaining more information about reaction mechanism, we have madeadditive experiments. The preliminary conclusion can be obtained. For this system, theprimary alcohol and secondary alcohol are firstly oxidized to the corresponding aldehydeand ketone reapectively, and the alkali provides required alkaline environment, then the aldolcondensation is followed between the aldehyde and ketone to produce α,β-unsaturated ketone, finally, Michael addition reaction reduces C=C to α-alkylation ketone,the final carbonyl group is reduced in situ to senior alcohol as target product. However, otherreaction lines are not excluded at present. Our lab is making the study on the reactionmechanism using quantum computational chemistry.Thirdly, we make preliminary exploration about the possibility of β-oxidative alkylationof secondary alcohols with cheap metal (especially iron catalyst) activated primary alcohols.The different influence factors of oxidative alkylation reaction are mainly examined, forexample: the kinds of catalysts, the alkali types, reaction temperature, reaction time and theratio between catalyst and alkali, etc, Up to now, the perfect synthesis conditions are2%acetylacetone ferrous as catalyst,20%sodium hydroxide providing alkaline environment,0.5mL p-xylene as reaction solvent, magnetic stirring at140oC for12h with GC yield at69%.It belongs to one-step reaction for direct β-oxidative alkylation of secondary alcoholswith cheap metal (especially iron catalyst) activated primary alcohols. The used catalysts arecheap metals which are simple and easy to get. This reaction process does not require anyligand, hydrogen donor (acceptor), or foreign hydrogen source and only needcatalytic amount of alkaline to finish the reaction. It decreases the reaction difficulty,improves atom efficiency and is suitable for the requirement of green chemistry andsustainable development. These works not only deepen our understanding and knowledgeabout cheap metal catalyst, especially iron catalyst, but also extend the application of ironcatalyst in organic synthesis reactions.