Facilitator: Chris Lovero Organic Chemistry II Reactions 1 Task Reaction NotesSymmetrical ethers through dehydration of 1o alcohols*cannot be unsymetrical (you will get mixtures!)ROHx 2RORH2SO4140oCCleavage of ethers byvstrong acidsOCH3HBrBr+CH3BrOHBrOHBr*can also use HI, HCl, etc* vinyl or aryl do not get cleaved (NO SN2 ON SP2)AutoxidationRO HRRO2 (xs)slowRO ORROH+OO HRRR*basically forms peroxides.... which EXPLODE!MCPBACH3CH3CH3CH3OMCPBA*epoxide will form along the more substituted alkeneIntramolecular WilliamsonBrOHNaOHOCH3OHClNaOHOCH3*SN2 like*forms O- that attacks halogenated CH3O+H2OCH3DOCH3DOHOHCH3DO1)-OH2)H3O+OHOHDCH3Opening of Epoxides*activate the O first*weak Nu are good*more substituted side attacked*SN2 like (least subs) so strong Nu and base*Grignard reagent and acetylide anion can work toooFacilitator: Chris Lovero Organic Chemistry II Reactions 2 Task Reaction NotesFree Radical Halogenation ExpandedCH3CH3NBShv 0oC*Low T: more stable TS*High T: more stable compoundCH3CH3BrCH3CH3BrCH3CH3CH3CH3..transition stateNBS60oCConjugated SystemsCH2CH2HBr*in this example we will examine the case of HBrBr2H3O+HBr / 0oCHBr / 40oCCH2HBrBrH++transition state*Low T: more stable TS*High T: more stable compound*NOTE: If more than one conjugated system possibly exists, examine the transition states of each one and do the reactions with the more stable transtion states!Diels-Alder ReactionD = donating group W = withdraw groupD+WheatDWDW+heatDW*1,2 or 1,4 adduct*know endo rule*Diene and Dienophile*Know Stereochem*PRACTICE THIS!!!Facilitator: Chris Lovero Organic Chemistry II Reactions 3 Task Reaction NotesNOTE: FROM HERE, YOU HAVE TO KNOW YOUR META, ORTHO, AND PARA DIRECTORSHalogenation of BenzeneX2, FeX3 or(I2 / CuCl2)X*X = Cl or BrHNO3H2SO4 heatNO2Nitration of Benzene*H2SO4 acts as a catalystSO3 / H2SO4 heatSO3H*REVERSIBLE DUE TO ENTROPYSulfonation (fuming sulfuric)+H2SO4SO3H+H2OFriedel-Crafts AlkylationRClAlCl3R*watch rearrangement!*no strong deactivators (no strong W grps)*no amino groups*watch for polyalkylationFriedel-Crafts AcetylationAlCl3ROORCl*no strong deactivators (no strong W grps)*no amino groupsCO / HClAlCl3 / CuClHOGatterman-Koch Formation (forming benzaldehyde)*no strong deactivators (no strong W grps)*no amino groupsClemmensen ReductionROZn(Hg)HClR*avoid using this reactant in the presence of alkenes, alkynes, alcohols and amines.Facilitator: Chris Lovero Organic Chemistry II Reactions 4 Task Reaction NotesNucleophilic Aromatic Substitution of Aryl Halides: Addition / EliminationWWWX Nu (2eq)heat, pressureWWWNu*need Strong W groups ortho and/or para to leaving group.*Nu can be OH-, RO-, NH3.*NOTE: If - OCH3 is the Nu, only need 1 eqW = withdraw group X = leaving grp (halide) Nu = nucleophileNucleophilic Aromatic Substitution of Aryl Halides: Elimination / AdditionCH3XNaNH2 /NH3 (l)CH3NH2+CH3NH2X1) NaOH (2eq) / 340oC / 2500 psi2) H3O+OH*occurs when Strong W group is not O/P*formation of benzyne in mechanism* Nu can be OH-, RO-, -NH2.*will get a mixture (like second example)Chlorination of Benzene3 Cl2 / heatpressureClClClClClCl*8 different stereochems actually occur*this particular molecule is the commercial compound Rid (lice killer)Catalytic Hydrogenation3 H2 / 1000 psi / 100oCRu or Rh (Pt,Pd,Ni also)Birch ReductionWDNa0 or Li0NH3(l) / ROHWD*withdraw groups -> sp3*donating groups -> sp2Reduction of Nitro group into Amino GroupNO2Zn, Sn, or FeHClNH2*Do not confuse with Clemmenson Red.Facilitator: Chris Lovero Organic Chemistry II Reactions 5 Task Reaction NotesSide Chain Rxn: Oxidation*Can use either reagent*Does not work for bulky groups.(CH2)nOKMnO4/H2OOH-/100oCNa2Cr2O7 / H2SO4 heatCO2HCO2HCO2HHO2CHalogenation of side chainsCH2CH3Cl2 / lightClCl+54% 44%Br2 (or NBS) / lightBr*If aromatic ring is activated, use NBS instead of Br2*Pay attention to Temp (if it's low or high)*WILL EXPLAIN THIS BETTER IN CLASSNucleophilic Subs of Benzylic HalidesCH2BrCH3OH heat++ major!*SN1 or SN2 or E2? Depends on conditions!*Resonance form that does not disrupt the aromaticity is more stableCH2OCH3*SN1BrCH3CH2O- Na+ NaI acetone*SN2*E2IRxns of phenols similar to alocholsOH NaOHRCO2Hor RCOClPBr3O-ORO(no rxn)OH(no rxn)*2nd rxn is Fischer Estherification*3rd rxn is only one that is different!Facilitator: Chris Lovero Organic Chemistry II Reactions 6 Task Reaction NotesOxidation of Phenols to Quinones*This reaction forms a D-A dienophile!OHOH Na2Cr2O7 H2SO4OOFormation of Salycilic AcidOH1) NaOH2) CO23) H3O+OHOHO*Phenoxide anion can react with the weak electrophile because it is so strongly activated.REVIEW: Oxidation of alcohols2o alcoholsOHNa2CrO7H2SO4 / H2OCrO3 / H2SO4 / H2Oacetone / 0oC(Jones reagent)PCCCH2Cl2O*any [ox] can be used*KMnO4 and NO3 can be used but they are harsh.1o alcoholsOHPCCCH2Cl2OH*Only use PCC because Jones reagent will yield carboxyllic acidREVIEW: Cleavage of Alkenes by OzonolysisCH3HCH3CH31) O32) (CH3)2SOCH3HOCH3CH3+REVIEW: Hydration of AlkynesRHH2O / H2SO4HgSO41) Sia2BH2) H2O2 / OH-RR1eitherreagentHHROHOHHRHCH3RORCH2OHmixture of ketones*Really know the mechanism now and how the enols tautomerize.Facilitator: Chris Lovero Organic Chemistry II Reactions 7 Task Reaction NotesDithiane Synthesis of Aldehydes and Ketones*Dithiane will be given*BuLi = CH3(CH2)2CH2-Li*Halide must be methyl or 1oSSHH1) BuLi2) R - XSSRH1) BuLi2) R1 - X H3O+ HgCl2RHOSSRR1 H3O+ HgCl2RR1OKetones from Carboxylic AcidsROHO1) R1 - Li (2eq)2) H3O+RR1O*2 eq because first is used to make saltKetones from NitrilesCNR1) R1-MgX2)