SN1/SN2/E1/E2 Decision Framework"Master Organic Chemistry"masterorganicchemistry.comNote - this sheet is not meant to be comprehensive. Your coursemay provide additional material, or may not cover some of the reactions shown here. Your course instructor is the final authority.Omissions, Mistakes, Suggestions? [email protected] sheet copyright 2015, James A. Ashenhurstmasterorganicchemistry.comDo you see Br, Cl, I, OTs, OMs, or other similar good leaving group present?Is an alcohol (OH) presentIs it attached to an sp3 hybridized carbon (i.e. a carbon with no multiple bonds)PrimaryIs the nucleophile a strong, bulky base (e.g. tBuO )E2 (but with formation of leastsubstituted alkene)Secondaryand attached to sp3 hybridized carbonIs acid being added? If so, identifyHCl, HBr, HIH2SO4, TsOH, H3PO4Identify Carbon Attached To Leaving GroupIs the nucleophilestrongly basic?Good nucleophile present?TertiaryTertiary alcohol?concertedH shift w/subsequentE1 (rare)Is a good nucleophile or strong base present?Polar Protic solvent?Carbocation formation:Is rearrangement possibleto give a more stablecarbocation?Strong base present?Heat applied?YESNONOYESYESNO1°2°3°YESNOSN2YESNONOIs the solvent polar aprotic?YESNOYESYESNOYESYESNOYESNONOYESNONOYESTertiary alcohol?YESPrimaryalcohol?YESNONOSecondaryalcoholLeaving Group AbilitySlow SN2SN2SN2SN2E2E2YESRearrangement (hydride or alkyl shift)NOSN1SN1SN1NO REACTIONE1E1Carbocation formation:Is rearrangement possibleto give a more stablecarbocation?YESRearrangement (hydride or alkyl shift)NOSN1Here, HCl, HBr, and HI have nucleophiliccounter-ions, whereas H2SO4, TsOH, and H3PO4 do notAlkenyl and alkynyl halidesdo not participate in these reactionsCH3SN2SN2SN2SN2Primaryalcohol?SecondaryalcoholSome variability here; E2 willstrongly competeRule of thumb: pKa ofconjugate acid is above 12Carbocation formation:Is rearrangement possibleto give a more stablecarbocation?YESRearrangement (hydride or alkyl shift)E1NOHeat generally favorselimination reactionsPolar ProticDMSOCH3OH (MeOH)CH3CH2OH (EtOH)H2O(CH3)3COH (t-BuOH)CH3COOH (AcOH)HMPACH3CNCH3CCH3OAcetonitrileAcetone(Dimethyl Sulfoxide)DMFIn general, solventswith O-H or N-HbondsExcellentI BrClTsO MsOH2OGoodR3NCH3COOPoorHORONon leaving groupsH RNH2SolventsPolar AproticN,N-Dimethyl formamideThe weaker the base,the betterthe leaving groupBase StrengthNucleophilicityExcellentN3CNHS RSHHOC CROGoodFFClBr IROOR3N R2NHRNH2PoorR–SHH2O R–OHROOHEssentially Non-nucleophilicHHSO4(CH3)3COStrong BasesHO ROH RNH2(CH3)3COHC CNR2For more background see the summary sheet on SN1/SN2/E1/E2due to steric hindranceNote: applying this framework mindlessly without understanding the concepts and variables behind each of the four major reactionsis unlikely to lead to success. Usage of this framework assumes youare familiar with the following concepts:•What makes a good nucleophile•What makes a good leaving group•Strength of acids and bases•Factors that affect carbocation stabilityIt also goes without saying that it is absolutely necessary to be able to draw the products of each reaction, including stereochemistryTsO* this can be very instructor-dependent!!best to check this with your