Organic Chemistry I: Reactions and Overview - …

1 OrganicChemistryI:ReactionsandOverviewAn drewRosenEditor:RaghavMalikJanuary13,201 3 ContentsILibraryofSyntheticReactions3I IOrganicTrendsandEssentials41 onComp ersionForces(Polarizability).. o I XandH ,Dihydroxy,andCarb onylComp onylComp Notethatthisisapartiallistofreactions1 GraphicsareobtainedmostlyfromStonyBro okUniversityCHE327 PowerPointslidesand OrganicChemistry , IOrganicTrendsandEssentials1 ondsastructurehas, (formalcharges) ositivechargesonthemoreelectrop ositiveelementsaremorefavorable22 FamiliesofCarb onComp ersionForces(Polarizability) olarizablethanatomswithonlyb atter( longchains )havemoresurfaceareaandthushavelargerdis p Adegreeofunsaturationiseithera b ondoraringstructure Formula.

2 2C+ 2 +N H X2wherethevariablesarethenumb erofcarb ons(C),nitrogens(N),hydrogens(H),andhalo gens(X)3 AnIntro ectingAcidity(indecreasingsigni cance)3 (scharacter)2 Forthepurp osesofdrawingallresonancestructures,itis notconsideredaviolationoftheo ctetruleifasecond-rowelement,likecarb on,hasfewerthanano ,itisusuallyafairlygo o ARIO Explained: Atom:Lo okatwhatatomthechargeisonfortheconjugate base. Foratomsinthesamerow, erio dictableanatomis, 'snegativechargeisonamoreelectronegative atom,itismorestable,andthustheparentacid isstronger. Foratomsinthesamecolumn,weconsideranatom ' erio dictableanatomis,theb 'snegativechargeismorestabilizedonanatom furtherdownagroup,itisamorestablemolecul e,andthustheparentacidisstronger.

3 ResonanceStabilization:Lo ,thestrongertheparentacidis. InductiveE ect:Lo okforinductivee 'snegativecharge, ,iftherearemanyalkylgroups,thisisapro cesscalledhyp erconjugation,andtheparentacidisactually lessstable. Orbital:Lo Theaxialgroupsb ecomeequatorialandviceversa Whendoingaring ip,whetheragroupisupordowndo esnotchange ChairConformation1:ChairConformation2(af terring ip): Whenp erformingachair ip,eachatomisrotatedonesp otintheclo ckwisedirection Amoleculeismorestablewhensterichindrance isminimizedandbulkysubstituentsareequato rialasopp osedtoaxial5 Stereo ,2,3, eassignedonthebasisofatomicnumb eroftheatoms, cessiscontinueduntiladecisioncanb emadeatthe rstp ointofdi (a)Step1:Step2 (downward):Analyzeifthenumb ers(1 2 3 4)goclo ckwiseorcounterclo ckwiseindicatesthatthemoleculeis R, whilecounterclo ckwiseindicatesthemoleculeis S.

4 (upward):Analyzethis intermediate moleculetoseeifthenumb ersgoclo ckwiseorcounterclo ckwiseindicatesthattheoriginalmoleculeis S, whilecounterclo ckwiseindicatesthemoleculeis R. Adeprotonationstepisrequiredtocompleteth ereactionwhenthenucelophilewasaneutralat omthatb oreaprotonExampleshowingdeprotonation4 o cationStability OrderofCarb o cationStability:3 >2 >1 > ectingtheRatesofSN1andSN2 Reactions Simplealkylhalidesshowthefollowingtrendf ororderofreactivityinSN2reactions: Methyl>primary>secondary (tertiary-unreactive)4 DeprotonationisnormallyseenasH3O+inwater ,butwhenthereisadi erentsolventinexcessitwillb edi erent6 TheratesofSN2reactions(notSN1)dep endonb oththeconcentrationandidentityoftheattac kingnucleophile Inaselectionofnucleophilesinwhichthenucl eophilicatomisthesame,nucleophilicitiesp arallelbasicities.

5 RO >HO RCO 2>ROH>H2O Nucleophilesparallelbasicitywhencomparin gatomsinthesamep erio d Nucleophilesdonotparallelbasicityand,ins tead,parallelsizewhencomparingatomsofthe samegroup Theb estleavinggroupsareweakbasesaftertheydep art PolaraproticsolventsfavorSN2andp olarproticsolventsfavorSN1 Mostofthesolventswithabbreviatednamesare p Highertemp eraturesincreasetheratesofeliminationrea ctions Apro ductwithamoresubstituteddoubleb ondismorestableandthusmorefavorable Iftert-butoxideisused,stericsmustb econsideredto Note:Itisdebatable,butsecondarymolecules canhaveSN1orE1inp TodetermineEorZ,lo okatthetwogroupsattachedtoonecarb onatomofthedoubleb ,rep eatthisattheothercarb onatom. Ifthetwogroupsofhigherpriorityareonthesa mesideofthedoubleb ond,thealkeneisdesignatedZ.

6 Ifthetwogroupsofhigherpriorityareonopp ositesidesofthedoubleb ond, Thetransisomerisgenerallymorestablethant hecisisomer Thegreaternumb erofattachedalkylgroups, ectingEliminationReactions Anon-bulkybasefavorsthemoresubstituteddo ubleb ondwhileabulkybasefavorsinmakingthelesss ubstituteddoubleb Rearrangements,alsoknownas1,2shifts,cano ccurinprimaryandsecondaryalcoholdehydrat ion Themorefavoredpro ductisdictatedbythestabilityofthealkeneb eingformed Fordehydrationofsecondaryalcohols,thep ositivechargeisshiftedthroughahydrideshi ftoralkylshift Forthedehydrationofprimaryalcohols,acarb o ,rearrangementscanstillo 's b ondisbrokenwhenahydrogenatomfromtheacidb ondstothecarb ontoformacarb o ccursasusual. Aringcanchangeinsizeduetoamethylshift,es p elow: Note:Neverdotwomigrations8 PartI I Occurswithinversionofcon guration Iftheb ondtoachiralitycenterisbroken,thereisani nversionofstereo AnSN1reactionwillcauseracemizationifenan tiomersarep ossiblepro Theremustb Alkynescanb esynthesizedfromalkanesviacomp oundscalledvicinaldihalides,whicharecomp oundsb earingthehalogensonadjacentcarb ons ItrequirestheuseofNH 2,whichcanfrequentlyb Aprimaryhalideandastrongbasemustb o MetalcatalyzedH2additiontoanalkyne(eg:H2 /Pd-C)pro ducesanalkane ControlledmetalcatalyzedH2additiontoanal kyne(eg:H2andLindlar'sCatalyst5)pro ducesanalkenewithsyn-addition(cis).

7 ThisisalsoforH2/Ni2B(P 2) Chemicalreductionofanalkynepro ducesanalkenewithanti-addition(trans).So ,C2H5withNH4Cl10 AlkenesandAlkynesI XtoanAlkene Markovnikov,notstereosp eci c,andrearrangementsarep Markovnikov,notstereosp eci c,andrearrangementsarep oration-Oxidation Mercuration-Demercuration:Markovnikovadd ition,antistereo Chemistry ,andnorearrangements UsesHg(OAc)2,H2 OandthenNaBH4,NaOH Hydrob oration-Oxidation:Anti-Markovnikovadditi on,synstereo Chemistry ,andnorearrangements UsesBH3andthenH2O2,NaOH5 Lindlar'sCatalystisPd/CaCO3 XandH Ahalohydrinispro ducedwhenthehalogenationofanalkeneiscarr iedoutinanaqueoussolutionasopp osedtoanon-nucleophilicsolvent Ifthealkeneisunsymmetrical, O3orKMnO4canp erformoxidativecleavageofalkeneswithsyna dditions(usefulforaddingmultiplehydroxyl groups) Hot,basicKMnO4cleavesthedoubleb onsareoxidativelycleavedtoketones,monosu bstitutedalkenecarb onsarecleavedtocarb oxylicacids,andunsubstitutedalkenecarb onsareoxidizedtocarb ondioxide.

8 Usingozone-ozonolysis-istheb estmetho dtocleavealkenesandcanop enupcycloalkenes, , Fordetailsofthisreaction,seethetableb elow Itisimp ortanttokeepthebackb onethesametoensureprop erstereo ,Dihydroxy,andCarb Alkynesshowthesamekindofhalo-additionasa lkenes(anti-addition) Additionmayo ccuronceortwicedep endingup AlkynesreactwithonemolarequivalentofHXto formhaloalkenesandwithtwomolarequivalent stoformgeminaldihalidesviaMarkovnikov'sR ule Anti-Markovnikovadditiono ccurswhenp Oxidativecleavageofalkyneswithozonewilly ieldtwocarb X Racemicmixturesarepro ducedifenantiomersarep ossible Rearrangementsarepresent Methanoland1 and3 Convertsa1 or2 alcoholtoaleavinggroupwithoutrearrangeme nts Inversionofcon gurationo UsingeitherpyridineorDMAP,sulfonateester scanb epreparedfromcombininganalcoholwithachlo rinatedsulfonatederivative Thereisretentionofcon Alcoholscandehydratetoformalkenes, ,1 alcoholscandehydratetoformethersbythefol lowingmechanism.

9 Acid-catalyzeddehydrationisnotusefulforp reparingunsymmetricalethersfromdi erent1 alcoholsb ecausethereactionleadstoamixtureofpro ducts(ROR,ROR ,andR OR ) Alkoxymercuration-demercurationisametho dforsynthesizingethersdirectlyfromalkene s,likeintheexampleb elow, Toaddaprotectinggrouptoanalcohol,useTBDM S inpyridine Toremoveaprotectinggroup,a uorineanioncanb oxides Ep oxidationisasynadditionthatisstereosp eci c RCO3 Hcanb eusedtomakeanep oxidefromanalkene: Therearetwotyp esofreactionsthatep oxidesgothrough:Acid-CatalyzedandBase-Ca talyzed(b othring-op eningandanti-con guration) Usetheacronym BLAM Basic=LessSubstitutedAcidic= oxideReactionSummarywithExampleExampleof BLAM :12 AlcoholsfromCarb onylComp onylComp ounds Reductionconvertsacarb oxylicacidtoaprimaryalcoholbytakingo anoxygenfromC O Reductionconvertsanesterintotwo1 alcohols,onederivedfromthecarb onylpartoftheestergroupandtheotherfromth ealkoxylpartoftheester Reductionconvertsaketonetoa2 alcoholandanaldehydetoa1 alcohol PCCwillconverta1 alcoholtoanaldehydeandoxidizea2 alcoholtoaketone(notusefulfor3 ) KMnO4orH2 CrO4(JonesReagent)canoxidizea1 alcoholtoacarb oxylicacid H2 CrO4canoxidizea2 GrignardReagentsreactwithanycomp oundthathasahydrogenattachedtoanatomofhi ghelectronegativity(eg:oxygen,nitrogen,s ulfur,etc.)

10 Andreactwellwithcomp oundsthathavecarb onylgroups19 So Br2andheat/lightcanp erformthefollowinghalogenadditiontothemo resubstitutedcarb onofanalkane: HBrwithap eroxide(ROOR)willhavethebromineaddedtoth eleastsubstitutedcarb Cl2andheat/lightaddsachlorineatomtoanalk ane;however,itisonlyusefulsyntheticallyw henallp ossiblereplace-mentsyieldthesamecomp ound( entaneandCl2)20