REACTIONS AND MECHANISMS For Final Exam - Cook Group

REACTIONS AND MECHANISMSFor Final ExamReactions for Final ExamAlthough you don’t need to know all of the mechanisms for these reactions, knowing themmakes it easier to understand the reactions and to figure out a reaction if you forget it. Consult thelecture notes for more details on the mechanisms.ELECTROPHILIC ADDITION REACTIONSHXHg(O 2 CCF 3 ) 2CH 3 OHX+XOCH 3HgO 2 CCF 3NaBH 4OCH 3RHgSO 4OHORRH 3 O + enol ketoneOAlCl 3ClO(note this is really an electrophilic substitution reaction)OO O HCH 3 ClMCPBACH 3 HCH 33 O +OOHepoxideOHBr 2 , H 2 ONaHCH 3OHBrhalohydrinCH1) Hg(OAc) 2 H 2 O CH 3 32) NaBH 4OH© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

CH 3BH 3H 2 O 2 , OH - CH 3HOHCH 31) OsO 4 CH 32) NaHSO 3OHOHELECTROPHILIC SUBSTITUTION REACTIONSBr 2FeBr 3BrCl 2FeCl 3ClI 2CuI 2IHNO 3H 2 SO 4 NO 2SO 3H 2 SO 4SO 3 HR-ClAlCl 3ROR ClAlCl 3OROBr 2CH 3 CO 2 HOBrO1)Br 2 PBr 3OOH2) H 2 OBrOHNUCLEOPHILIC ADDITION REACTIONSROH1) NaBH 41) LiAlH 42) H 3 O + O2) H 3 O +R OHR HR OHOR OCH 31) LiAlH 41) DIBAH2) H 3 O + O2) H 3 O + OR OHR OCHR H3OR OCH 31) PhMgBr2) H 3 O + OHRPhPhPhOHHCNKOHHO CNPh Hcyanohydrin© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

H + or - OHO catalyst+ H 2 OHO OHO+hydrateR-NH 2H + N RimineO+R 2 NHH +RN RenamineOH + RO OR+ 2ROHOan acetalOCH 3 NH 21,4-additionNHCH 3O1) Ph 2 CuLi2) H 3 O + 1,2-additionOPh1,4-additionO1) PhMgBr2) H 3 O + HO PhO1) PhLi2) H 3 O + HO Ph1,2-additionROCl1) PhMgBr2) H 3 O + HO PhRPhOR OCH 31) PhMgBr2) H 3 O + HO PhR PhC N1) CH 3 MgBr2) H 2 OOCH 3© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

O+ Ph 3 P CH 2phosphoniumylideCH 2+ Ph 3 P OO 1) NaBH 42) H 3 O + HO H1,2-additionO 1) LiAlH 42) H 3 O + HO H1,2-additionThe addition of hydrides to carbonyls is also considered reductions and more examples are listedunder reduction reactions.MgBrO C OOOMgBrH 3 O +OOHELIMINATION REACTIONSH 3 COHH 2 SO 4CH 3E1OHPOBr 3pyridineE2ONH 2ClOS ClC NOBrpyridineOSUBSTITUTION REACTIONS (S N 1)CH 3OHHClCH 3OHH-H 2 OCH 3Cl© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

CH 3OHClCH 3O H(regioselective like S N1 but stereoselective like S N2)ClCH 3 ClOHSUBSTITUTION REACTIONS (S N 2)OHClOSClHOOSCl ClOHBrBrPBrHBrOPBr BrOHClOSTos-ClO TospyridineOH1) NaH2) CH 3 IO CH 3O HI HOIHO+IHO HCl OClOHClO1) PhMgBrOHPh2) H 2 OPhSHCH 3 IPh S CH 3ONaOHOCH 3 IOROHRONaR OCH 3O1) LDA2) CH 3 IOCH 3© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

OONaOEt, EtOHOOEtOOEtRBrEtOROEtH 3 COOOEtNaOEtEtOHRBrH 3 COOROEtSUBSTITUTION REACTIONS (Nucleophilic Aromatic and Nucleophilic Acyl)ClOHO 2 N NO 2NaOHO 2 N NO 225 °CNO 2NO 2ClHNaOH340 °C2500 psiOHHbenzyneintermediateROOH+ SOCl 2R ClO+ SO 2 + HClROOH+HOORHeatROOOR+ HOHOHAOROHR'OH R OR'ROCl+NaOORROOOR+ NaClROCl+ H 2 OROOH+ HClROCl+ R'OHpyridineROOR'+ Pyridine-HClROClO+ 2 NH 3R NH 2+ NH 4 ClO1) Ph 2 CuLi2) H 3 O +ORClRPh© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

OOO+ H 2 O2OOHOOO+ ROHOOR+OOHOOO+ NH 3ONH 2+OOHOR OCH 3+ H 2 ONaOH (cat)ROONa+CH 3 OHHO C NPhHH 3 O + HOOC OHPh HOR NH 2+ H 2 OHA (cat)ROOH+ NH 4 AOCH 3I 2 , NaOHOO+ CHI 3iodoformOXIDATION REACTIONSOH CrO 3ORRH 3 O + R ROH CrO 3ORH 3 O + R OHOHPCCORRHO CrO 3ORHH 3 O + R OHOOKMnO 4OHOHO© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

KMnO 4OCOHOKMnO 4OCOHOOHKMnO 4 2O1) O 32) Zn, AcOH+HOREDUCTION REACTIONS (note - hydride addition to carbonyls is also listed under thenucleohpilic addition section)O1) NaBH 42) H 3 O + R OHRHROHO1) LiAlH 42) H 3 O + R OHRHO1) LiAlH 42) H 3 O + R HR OCH 3O1) DIBAH2) H 3 O + OR OCH 3R CN1) DIBAH2) H 3 O + ORHHOC N1) LiAlH 42) H 3 O +HO NH 2PhHPhHO1) LiAlH 42) H 3 O +ROHROH© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

O1) BH 32) H 3 O +ROHROHROCl1) LiAlH 42) H 3 O +ROHO1) LiAlH(Ot-Bu) 3ORCl2) H 3 O + R NH 2RHO1) LiAlH 42) H 2 ORNH2O H 2 N NH 2KOHN NH 2HHa hydrazoneCH 3H 2Pt, 2000 psiCH 3orRh/C, 15 psiOPd/CH 2Pd/CNO 2H 2Pd/CNH 2NO2SnCl 2NH 2H 3 O +© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

OTHER REACTIONSNBSperoxidesBralso benzylicbromination+EWGEWGCl+KNH 2benzyneintermediateOheatOOHHOheatOOHHO(CH 3 ) 2 CuLiORClR CH 3HO C NPhHH 3 O + HOOC OHPh HOOH 3 O + , HeatOEtOOEtHOR + CO 2RH 3 COOOEtH 3 O + , HeatH 3 COR+ CO 2R© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

MECHANISMSElectrophilic Aromatic SubstitutionNEED TO KNOW MECHANISMBrBrHBrHBrHBr-HBrBrCarbonyl Addition ReactionsNEED TO KNOW MECHANISMMechanism for Imine FormationOHAHOH 2 N RHOH HNRAHOHNRHemiaminalUp to here this isidentical to a hydrationwith amine asnucleophile instead ofwaterHAN RAHNRHNR-H 2 OHHOHNRimineresonance structures© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

Acyl Substitution ReactionsMechanism for Enamine FormationNEED TO KNOW MECHANISMOHAHOHN RRHOR HNRAHORNRHemiaminalHARN RAHRNRRNR-H 2 OHHORNRenamineresonance structuresThe only difference is this last step. There is noproton on the nitrogen to come off, so a protonis taken off of the alpha carbonMechanism for Acetal FormationNEED TO KNOW MECHANISMOHAHOHOHO RHOO H RAHOO RHAHOHO Rresonance structuresHemiacetal-H 2 OROO RARHOO RROHO RO Rresonance structures© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

NEED TO KNOW MECHANISMFischer EsterificationOHAOHR'OHHHO OR'AHO OR'ROHROHROHROHHAOAOHHO OR'HO OR'ROR'ROR'RROHHNEED TO KNOW MECHANISMSAcid Catalyzed HydrolysisOHAHOHOH 2 OHOHOHAHOO HOCH 3OCH 3OCH 3OCH 3OCH 3HAOAHOHOHOO HOHOHOH- HOCH 3OCH 3HBEST METHODBase Catalyzed Hydrolysis (Saponification)OOCH 3OHOOHOCH 3OOHO+ OCH 3O+ HOCH 3Rapid acidbasereactiontakes placeCarboxylate is a thermodynamicsink and makes the reactionessentiall non-reversible. To getthe carboxylic acid, add acid toprotonate.© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

NEED TO KNOW MECHANISMAcid Catalyzed Hydrolysis of AmidesOHAHOHOH 2 OHOHOHAHOO HNH 2NH 2NH 2NH 2NH 2HAOAHOHOHOO HOHOHOHNH 2H© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

Other Mechanisms that may be useful but do not need to know.ClO 2 N NO 2NaOHCl OHO 2 N NO 2Cl OHO 2 N NO 2Cl OHO 2 N NO 2NO 2NO 2NO 2NO 2Acid Catalyzed Dehydration - E1 eliminationCH 3OHH + CH 3 HO-H 2 OCH 3HH3° alcohol oxonium is abetter leavinggroup than alcohol3° carbocationbaseCH 3POBr 3 Promoted Dehydration - E2 eliminationOHOPBr Br BrHOOPBrBrNpyridinemild baseOO PBrBr2° alcoholHGood LeavingGrouppyridineAcid Promoted Substitution - S N 1 - 3° AlcoholsCH 3OHHClCH 3OH-H 2 OCH 3HH3° alcohol oxonium is abetter leavinggroup than alcohol3° carbocationClCH 3Cl© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

Electrophile Promoted Substitution - S N 2 - 1° and 2° AlcoholsOHClOSClHOOSClClCl2° alcoholGood LeavingGroupInversion ofConfigurationOHBrBrPBrHOBrPBrBrBr2° alcoholGood LeavingGroupInversion ofConfigurationOHH +OHHHOS N 2OH-H +OHO Br NaHBrOOBase Catalyzed HydrocyanationHCNbaseOCNOCNHCNHOCNPhHPhHPhHcyanohydrinH 3 O + Ph HHOPhC NHheatHOOCOHHOPhC NH1) LiAlH 4HO NH 22) H 3 O + Ph H© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

Wittig ReactionO+ Ph 3 P CH 2phosphoniumylideCH 2+ Ph 3 P Oylides are prepared by S N 2 reactions of phosphines with alkyl halides then deprotonationP+R X Ph 3 P RXHHbasePh 3 PRtriphenylphosphineS N 2triphenylphosphoniumsalttriphenylphosphoniumylideylides are nucleophilic and will react with carbonylsO+Ph 3 PROPPh 3Ph 3POa betaine+PPh 3OAcid ChloridesROOH+ SOCl 2R ClO+ SO 2 + HClClOS ClRO O ClOS ClHClbase (solvent or Cl - )(This step may happen later after kicking off HOSOCl)ROOOS ClORClOO S Cl© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University

OH + OH Br Br OBr+ HBrOBr 2OBrpyridineOCH 3 CO 2 HO1)Br 2 PBr 3OOHPBr 32) H 2 OBrOHH 2 OOBrH +OHBrBr 2BrOBrOCH 3I 2 , NaOHOO+ CHI 3NaOHiodoformOCH 2I 2OCH2IrepeatOCIIINaOHO OHC II I© Gregory R. Cook page Chem Exam Reactions and MechanismsNorth Dakota State University