Chemistry 0310 Organic Chemistry 1 Chapter 8 The Hydroxy Functional Group Alcohols Dr Peter Wipf Alcohols can act both as acids as well as bases the relevant pKa s for MeOH are 15 5 and 2 2 respectively The introduction of electron withdrawing groups can increase or decrease this values The synthesis of alcohol proceeds by way of SN1 AND SN2 reactions from halides or sulfonates In order to reduce the amount of elimination side products carboxylic acid salts can be used for their higher nucleophilicity and the resulting esters can be cleaved to the desired alcohols by treatment with aqueous NaOH a process known as saponification Another major route toward alcohols uses the reduction of carbonyl compounds LiAlH4 LAH and NaBH4 are the most common reducing agents and can donate 4 hydride ions each to a suitably electrophilic acceptor C O Organometallic agents such as organolithium and organomagnesium Grignard derivatives follow very similar mechanisms to hydride additions and provide a third major pathway to alcohols The reverse reaction to reduction is oxidation Important oxidizing agents are PCC pyridine HCl and CrO3 Jones reagent CrO3 H2SO4 in acetone and KMnO4 The following table gives a brief summary of the reactions between major classes of functional groups and reducing oxidizing and organometallic agents A B acid base reaction simple proton transfer no reaction Mechanisms of these processes are provided in lecture notes and in the textbook Substrate RCH2OH RR CHOH RR R COH RCHO RCOR RCO2R RCO2H Reagent RCH2OH LAH A B A B A B RCH2OH RR CHOH HOR RCH2OH NaBH4 A B A B A B RCH2OH RR CHOH A B RCHO RCOR RCOOH RCOR RCOOH R Li A B A B A B RR CHOH RR R COH R MgX A B A B A B RR CHOH RR R COH PCC CrO3 H2SO4 RR R COH HOR RR R COH HOR RCOR A B Organometallic reagents can be prepared from the corresponding organohalides and Li or Mg metal Another important pathway is proton transfer to generate an organometallic compound of decreased basicity from a derivative of higher basicity The differential reactivity of different reducing oxidizing and organometallic agents allows the selective bond formation and structure manipulation a strategy that is employed in the process of retrosynthetic analysis Retrosynthesis is the process of deconstructing a target molecule into readily available starting materials by means of imaginary breaking of bonds disconnections and by the conversion of one functional group into another functional group interconversions OH Target Molecule Ph Ph pathway B pathway A OH OH Synthons Ph Ph Reagents Br Ph Ph O Ph BrMg Ph Synthons Reagents Ph