INTRODUCTION
Nucleophilicsubstitutionreactionsareamongthemostfundamentaltypesof
organicreactions.Ingeneral,wecandepictnucleophilicsubstitutionreactions
inthefollowingway:
Inthistypeofreactionanucleophile(Nu:)replacesaleavinggroup(LG)in
themoleculethatundergoessubstitution(calledthesubstrate).The
nucleophileisalwaysaLewisbase,anditmaybenegativelychargedor
neutral.Theleavinggroupisalwaysaspeciesthattakesapairofelectrons
withitwhenitdeparts.Oftenthesubstrateisanalkylhalide(R
)andthe
leavinggroupisahalideanion(X)
Innucleophilicsubstitutionreactionsthebondbetweenthesubstratecarbon
andtheleavinggroupundergoesheterolyticbondcleavage,andtheunshared
electronpairofthenucleophileformsanewbondtothecarbonatom.
TYPES OF NUCLEOPHILIC SUBSTITUTION REACTIONS
Therearetwotypesofnucleophilicsubstitutionreactionsbasedon
themechanismtheyproceedandthekineticsofthereaction.They
are:
a) SubstitutionNucleophilicUnimolecular(SN1)
b) SubstitutionNucleophilicBimolecular(SN2)
NUCLEOPHILE
Anucleophileisachemicalspeciesthatdonatesanelectronpairto
anelectrophiletoformachemicalbondinrelationtoareaction.
Anucleophileisareagentthatseeksapositivecentre.
Anynegativeionorunchargedmoleculewithanunsharedelectronpair
isapotentialnucleophile.
Allmoleculesorionswithafreepairofelectronsoratleastonepi
bondcanactasnucleophiles.Becausenucleophilesdonateelectrons,
theyarebydefinitionLewisbases.
Nucleophilicdescribestheaffinityofanucleophiletothenuclei.
E.g.,Hydroxylion(OH),water(H2O),ammonia(NH3),cyanideion(CN).
LEAVING GROUP
Aleavinggroupisamolecularfragmentthatdepartswithapairof
electronsinheterolyticbondcleavage.
Toactasthesubstrateinanucleophilicsubstitutionreaction,amolecule
musthaveagoodleavinggroup.
Agoodleavinggroupisasubstituentthatcanleaveasarelativelystable,
weaklybasicmoleculeorion.
E.g.,Halideion(X),sulphonateesters,water(H2O),ammonia(NH3)
SUBSTITUTION NUCLEOPHILIC
BIMOLECULAR (SN2)
SN2reactionsfollowsecondorderkinetics,i.e.,theratedependson
concentrationofboththereactants.
Thenucleophileapproachesthecarbonbearingtheleavinggroupfrom
thebackside,thatis,fromthesidedirectlyoppositetheleavinggroup.
Asthereactionprogresses,thebondbetweenthenucleophileandthe
carbonatomstrengthens,andthebondbetweenthecarbonatomand
theleavinggroupweakens.
Asthenucleophileformsabondandtheleavinggroupdeparts,the
substratecarbonatomundergoesinversionofconfigurationits
tetrahedralbondingconfigurationisturnedinsideout.
TheSN2reactionproceedsinasinglestep(withoutanyintermediates)
throughanunstablearrangementofatomscalledthetransitionstate.
MechanismforanSN2reactionisasfollows:
Thefreeenergydiagramof
thereactionsshowsthat
thefreeenergychangeis
negative.Thereactantsin
oneenergylevelmust
surmountanenergybarrier
(thetransitionstate)in
ordertoreachthelower
energylevelofthe
products.
BallandstickmodelofageneralSN2reaction
AnSN2reactionrequiresanapproachbythenucleophiletoadistancewithin
thebondingrangeofthecarbonatombearingtheleavinggroup.Becauseof
this,bulkysubstituentsonornearthatcarbonatomhaveadramaticinhibiting
effect.
SUBSTITUTION NUCLEOPHILIC
UNIMOLECULAR (SN1)
TheSN1reactionisanucleophilicsubstitutionreactionwheretherate
determiningstepisunimolecular.
Thereactioninvolvesacarbocationintermediateandiscommonlyseen
inreactionsofsecondaryortertiaryalkylhalidesunderstronglybasicor
acidicconditions,withsecondaryortertiaryalcohols.Withprimaryalkyl
halides,thealternativeSN2reactionoccurs.
RACEMIZATION
Racemizationreferstotheconvertingofanenantiomericallypure
mixture(onewhereonlyoneenantiomerispresent)intoamixture
wheremorethanoneoftheenantiomersarepresent.
Iftheracemizationresultsinamixturewheretheenantiomersare
presentinequalquantities,theresultingsampleisdescribed
asracemicmixture.
Racemizationtakesplacewheneverthereactioncauseschiralmolecules
tobeconvertedtoanachiralintermediate.
STEREOCHEMICALASPECTSOFSN1REACTION
AnSN1reactionproceedswithracemization.
TheSN1reactionproceedsthroughtheformationofanintermediate
carbocationandthecarbocation,becauseofitstrigonalplanar
configuration,isachiral.
Itreactswithnucleophileatequalratesfromeithersidetoformthe
enantiomersinequalamounts.
REACTIVITYOFALKYLHALIDESTOWARDSSN1&SN2
REACTIONS
ForSN1reactionsinincreasingorder
Primary
Secondary
Tertiary
ForSN2reactionsinincreasingorder
Tertiary
Secondary
Primary
FACTORS AFFECTING SN1
& SN2 REACTIONS
FactorsfavouringSN1 versusSN2 Reactions
Factor
Substrate
Nucleophile
Solvent
Leavinggroup
TABLE 6.
SN1
SN2
Methyl>1>2
3(requires
formationof
(requires
relativelystable
unhindered
carbocation)
substrate)
WeakLewisbase,
StrongLewisbase,
neutralmolecule,
rateincreased
nucleophilemaybe
byhigh
thesolvent
concentrationof
(solvolysis)
nucleophile
Polarprotic(e.g.,
Polaraprotic(e.g.,
alcohols,water)
DMF,DMSO)
I >Br >Cl >F forbothSN1andSN2
(theweakerthebaseafterthegroup
departs,
thebettertheleavinggroup)
