Types ofSmreactions

Snf Bimolecular Nucleophilicsubstitution rims

Said UnimolecularNucleophilicsubstitution rxns

Sni IntramolecularNucleophilicsubstitution exns

SNMP Nucleophilicsubstitution exnsby Neighbouring Group Participation

SNAE o Nucleophilicsubstitution exnsby addition elimination steps

snea Nucleophilic
substitution rxns
by elimination Addition steps
 Nucleophile
Nucleus phile tolove Nucleus
loving specie
1 Electron rich specie Anion bonepair and
pibond containing groups
Strong Nuo List

H0 D 0 T 0 00
11 0012 00
Ph N o_O Neo
RofFitz CHzcitao.ph c c0

Fo Ao Br0 I 0 8H 813 8Ph Nitz Konitz Rcoo_0 Good Nuo

WeakNuohist

1120 Haji R H RIoR RE R Rini Hcooit Revolt

solvent whichprovides the surface area of interaction bw reagents and substrates

solvent usually is chemically inert to both substrate and reagents

solvents

I
1
Nonpolarsolvent
1
PolarsolventCpe10
fµ o

Css coke NV E dielectricconstant

cits HighCT LowCb

I 1
Polarphoticsolventdoeshaveacidic Polarapnotesolvent
A
donothaveacidica
Hao Roh
fatzataciteatgat
abort
CHzutant
H city
cook
CHzuolt
noon
Phcooet

HasKSH KnitsRent
423N
 f
miffy Belt
Few Polarapnotesolvents
THF Dms Dimethylsulphide fatzs cud Dioyane f
ab 5
DME H Il n fzDimethylformamide Dmso Dimethyl
sulphonide at
0

DMA Dimethyl
acetamide CHz I N If i Ethers
R E R etao Mezo

HMPA Heyamethylphosphoramide cyclic ethers Crownethers jecrown

IT
TO OT
Eg lacrown g Yo
1
k1 iscrown o
o o
It

Nucleophilicity electronpain donor and bond forming with atom otherthan H

is called Nucleophile and this phenomenon is called Nucleophile

city
H d
n LG0
do Ht d0 city G Caz I
Base
Nucleophile

M 8 is a measure
of how readily an atom donates its e pain to
other e deficientatom It is characterized
by rate constant k making it a kinetic

property

Basicity is of howreadily an atom donates its pair to

a measure electron

a proton It is characterised
by equilibrium constant Kb and is therefore

a Thermodynamic property

Notes Proton is spherical so no need to see orientationduring basic strength but

for nucleophilicstrength we need to consider orientation also

 city strength
Nucleophile

Inudeophile atom
when donor is from sameperiod
Nucleophilicity a basicity a n

Nu0 Order CHF NHI otto T E0

Nitz Hai it

Basic City NH

Nucleophilic
015 70
atomfrom same group In Polarprotic
solvents
Effi
a size
h.gs nucleophile city 2
tf goodextentofoverlapfrombackside
Bro I0 to o orbital
city
Nucleophile F0 40
hereextraction proton neededtobedone
of
But basicity F0 do Bro I0 which is a spherical orbital

Egs NWOstrength OH0 s SH0 s sett0

Ha Haj Haie

NH s PHz s Asks

Note Above concepts are valid as long a solvent is PolarProtea

In polar Protea solvent Nucleophilic strength a

1
Basicstrength

In polar aprotiesolvent Nucleophilic strength x Basicstrength

In H2O I0 Bro do F0
Nucleophilicstrength
In DMF FO do Byo so

Basic F 40 Bro 20

solvent is not mentioned default is also protie

Note of
protie solvent
 alkanesRCH alkenesRCHCHz Amines RNA AmmoniaNH AlkynesRC CH
Ac
PhenolPhott Carbonic acid ROOHCHzCOOH PhoonsHOOK
AlcoholsROH H2O
RsozH c Haloacids Hd
HBrCHI
Picricacid c sulphonicacid

when nucleophilic atom is same but belongs to diff family of functional groups
nucleophilic strength o.O

itI EI 4a'IF nTIEd

Iii
n
m.ae donate e

Nucleophilicity a basicity

Equivalentresonating
ID CHz
CEO0 CHz Koo c cH5 o structures

Acetate ion CHzcoo0 is betternucleophilethen city so 0

o
11 0 0
stability atz Koo L Catz
f
o
o Nucleophilicity 7

Hao0
Overall Caza R c R fo F city
Nucleophile
1
Nucleophilic strength
stabilityofanion

4 sterically hindered bases are poor nucleophiles

citz
Eg CitgoO CHzof o_0 TestButoxide tBu8
methoxide
cuz
I I
Basic strength I 2

Nucleophilic strength I II

Eg Nucleophilic strength CHzo_O CHIHao

0
Caz dio_O Caz I o_0
CH3

1
city a
Nucleophile
stereohendererreel
crowding

n each a

no
Solvent effect on Nucleophilicity

Polar Protic solvent pps C ishigh

Eg CHg Br K CN to CHz CIN t KBR

Lf ppso
Hao

Koni hastwo parts k metale'on and CNOanion

Salt Mx is better soluble in PolarBoticsolvent Hao due to highdielectricconstant

Therefore Pps will solvate the ions M 4 XO to be large amount

Hao't g
o
i
soft i
g i o
H2O
Mfs1 H
Both Cation and anion gets highly solvated in PPS

go on0 being highly solvated its nucleophilic strength decreases and Caio

gets hydrated as well

Cow Pps always decreases the nucleophilicstrength and the solvent itself
acts like nucleophile and this reaction is called solvolysis

PolarApnotesolvent PAs E o butlow

8
CHz Br
1 Nat
CHzatzoo dryAggro CHz o cH2cHz
NaBr
U Snnew
sodEthoniede

PAs has good solubility towards MX there availability

of Mt x 0 will be in
sufficient amount

In PAs we have dense so centre whichsolvatesonlythe metal ion cation

but negatively charged Nucleophile Is not solvated so Nucleophile is readilyavailable

for the attack
 If PAS solvent is Ether Etao then
Eet
et s
Etyo
I Elite x 0 is not solvated hence have
i i s high ionic mobility and hence acts
et o's o et
I 1
et et like a good nucleophile

conclusion PAS Etzo THFDMS DMSO DMF DMA AMPA Acetone

crownethers

all will solvate the metal ion and increasing the nucleophilic

strength
of anion

Polarsolvent c no verylow snips

Non

Mx salt is Very less soluble or insoluble due to which the availability

of Nuo is for Sm reactions

less

pit eof Exo

s
o R M 90 lessfavourable
Nps

NP me Cd4 Csz etc

hexane

x 0 is hardly available hence Sov oars are

hasty going to takeplace

lon In NPs weak ionpair1M will be more soluble and will acts as
better nucleophile

µ1 0 ME m XO

Solubility of MX will decide the nucleophilic strength

NWOorder in Nps Fitz

Nato NatFitz NaOH NatF 0
weakionpair VeryhighIonic
character
 Nae order in Nps Naf L NII L MatBI a Nats
1 weak ionpair
1 meresoluble
BetterNuo

CFzsosH PKa 9
ons pka 8
heavenggooups.nu
0 posthugs 5 REnut Log

0Tf ONS OBS Ots Nz co

Super Log
o1g Triflate ion CFz fo P ONS Nosylation no sky o_0

Bs Boosylate ion i B foo_0 ots Tosylateion e foo_0

111
Nz Hao CHzott co are betterhearingGroups
Rott 1111 Eg REH HE

do Bro 10 are good hearing groups

F0 ok 0 cm0 NHI NRF 812 at c cH2 are Poor

leavinggroups

A Leaving Group is thepartof molecule that leaves the cationicpart of substrate wrote

with electronpair
More stable the Leavinggroup better is the leaving ability

oh weak Poor bases acts like good leaving groups

LeavingGroup comparisons

NHzcg Haole Rottle at roomtemp

Reason gaseous state

R NI Nitsg

R8H a Re Huo e
 NO Br me
o_0 o_0 o_0 EW Group
0 40 0 40 0 40
I I
I
Nos
l l
Br me

o_0
o 0 40
CFz I o_0 l
o
TI
nos
o
0
CHzCHao HEP C CHzCoo CHz
IfGood
o_0
Poor Moderate
VeryPoor
weak conjugate bases are good leavinggroups

FO L U0 a Bro IO 20 is weakbase
Reason size increases bondstrength
decreases and acts like betterhog

Cfg C o0 CHz 00
I
Reason due to I Effect
of Cts
Snfreaction Bimolecular nucleophilic substitution reaction

nuEhIqfig nut
y
his
I Nu Efg a

Transitionstate

f Logi R K NU subs
of the reaction
ENUOTER x
Rate R d
Bimolecularreaction Order 2

Graphs qate Rate

T T
1123 NUT

All feasible Snf reactions are exothermic reactions DH re weak0 bond is replaced

bystrong 5 bond
Energy Profile
as will be more like Rha substrate
Diagrams
Ea Hammond'sPrinciple

nwo Req Intern

RNu LG Yu L.gs

a et ez
line

singlestepreaction of

I cha
as Nut Lois Nu
NELLIE y my
Log

1 strong Nu
0
Transitionstate

usually unstable anions strong conybaseof

weakacids

strong Nuo I Bro NJ RP Ho PhotoRoooo

 Few
of the strong Nuo are

Hydroxide Ho
0 Thiohydroxide SH0

Alkoxide KO0 Thioalkoniede Rs0

Phenonide 1h00 Thiophenoniede 17h50

cyanide CN0 halides F 0 I9138,19

Nitrite 8N0 Hydride Ho
Neutral but strong Nuo NHz

Good hearing groups

d Br I o ER o fo R n 02 84
OTS OBS 0ns

Poor hearinggroups

F OH ok OPh SH SR NHz hence doesn't usually used

SN2 sins
for
Subtrates which doesn't
give Swa ran

Measons
2 Backside attack onthese x
B is not possible

Rx bond is too strong to be broken

Ange halides

f partial doubleboned character

Phenyl
 Also nuoµf8 f a
f f
Backside attack is not possible

To
X TYffae
double bondcharacter Cc

Ii Backside attack
ofNuo not possible

Veenylhalides donot show Sn2 ran

Pie
Wa Partial double bond character
CH CH IMf ha ggg

not Nu0 Backside attack is sterically hindered as it bond

will repel the incoming Nuo

Reasons
CHECK cl
1 Partialdouble boned character c x

Ii Backsideattack ofNuo not possible

30Alkylhalides heavy stereo crowding backside attackof Nuo

not possible
H H
CH3 May
CHz l X 11
Br X
fGt3
I muor
Nuff
X f Effy H
Bay

xs
a
 Log with f
c at 40carbon

Amylhalides CH3

City olI CHz Br X

g
Fnm
Too bulky to let Nuoapproach the 0 orbitalof
carbon
i Backside attack is not possible due to Stoic crowding
of
neo
group

L G at bridge head C atom

of substrate will not give Snperror
a
mE EeI
as one is in a cage like structure where Nao cannot reach

FT a

Eyocylic bonds show IT bond with carbon

characteristics
1
orbitals hence difficult to break C A bond

a
not
g
a nuoxrffffqf.tt
1 backside attack is not possible
I
X
i
f Ea x
Snp
1 due to backside attack being not possible

Poor Leaving Groups

A Sw2
X
Nuo 13 X
µ
if x OH MHz NRz SH SR oats OR 0th F ete

of Sn2 440.5m
Pyatt a breaking
of C x bond

i
sfnu if
o i
ie
Dy FL R d L 4 Br 13 I
O Rateof Saf
i weaker the C x bond more will be the rate of reaction
1 This Phenomenon is called elemental effect
1 Variation in the rate by change of element in the LG
1 It is observed during Sar
 Rate of Snp CHz x CHzCHz X y CH x city 4x
city

to as the bulkiergroups increases backside attack

of Nao
decreases

x 1
Snr rate
stericcrowding

Inversion in configuration Walden Inversion

se
nihqejE.ee
o
Luu a
HOT
Transition slate
Lf
Inductomericeffect

In Transitionstate when Lvg is pulling electionstowards itself then its

inductive effect increasing abruptly this type
of an effect is called
Inductometric Effect

se churner
Nuo G Nu Lug
fee
Transition slate

D D
o
I got a
EI Hoo me
5 i its
i Bff CaqKong
H H
114
Substrate Product
414 configuration inversiontookplace
Walden's inversion
A
loneemmemter

Any chloral position atom odd no of interchanges

a
lead to inversion of configuration
Even none interchanges lead to retention
of of configuration

D H D
Eg
8 z
Nat It I CHz
cuz
acetone
H D H

Eg
to
Br
ayKOH
apprott
niff
oo
p at b 50
CH CHz 50

Rate of reaction stability of 7 s

Ts
TSZ
se s Acetone
Ts3 I R I Nacl1
POE
Reactants
Tf Faf

Products

In case of Electron Donating groups present with pi bond

lone the d carbon it stabilises the transition
or
pair on
a 18
EDG
state
quo initTransitionslate E

a_
of stone
Experimental data
substrate Snfrelativerate Remarks
BU t z0

L
Ma
CH3 I 200 because
ofless sterichindrance
CH I 0.02 more steric crowding

d
so
pibond support in stabilising
Ts

Aa 120000 Reaction tends to become Snl

NUT U and 30 Carbocation is formed

d soo pibond support in stabilising

TS

MeO Chad 920 bone in

pair support stabilising

0 Ts
Ph c Chad 100,000 due to intermixingoftwoABMO a
lowerenergyorbital is producedwhich
is easilypenetrated ext na0
by
Reason As
per Mot
pn dkc.it DPD
Oo 7 11
0 2 Lower energy ABMO
e
NO
NO
entry
of LUMO
Order of Sni Ph RE CHIU Phated 0H34

9H56 7 d fee
Reactionsthrough Sw2

Williamson Ether Synthesis

Rooncato
St
R X
S dayether R o 13 t Naxf
strongmug Csw2ready

Alkoxide
x Cl Br I

X F CN oh D
R 1920allyl benzyl
RF 39Vinyl phenyl
neo

we know that 03 x
128

oX 5
R OH N X
may I fffgfj.am
zHzP
RFballgonide

I
o Hast 1

NAH Azt

U
a CHzCH20 Na XX
notSafready

EEL
b t Citzata I NaBrb
Sn seady Cindyether
Ethylphenylether
 l Br CHzatz o cha
c CHzCH2o Na

5m ready
Ethylbenzylether
Br Br

fly
i
Los
d CHzCH2o Na

bet

c
n
ABT wW Et
Ur
CHzCH28 DE
Lf
Me
Sna d
H H

f city Piva
CH5Bq
β CHz OCHS

1
D D

note Nu0 configuration doesn't change

H H

g CHz0 a
rLf por DE a Cayo CH3

LL D
SNZ
D
Walden's ersion
Retrosynthesis what are the suitable reactants to prepare the following
ethers

R O Na R Br Product

v
CHzo CHzel CHz O CHz
 R OoNa R Br Product

o_O CHzd o CHz

U i

0
c'ts
I case

O_0 O CH
CHzCl
i

X O

x x
of
x x
of
x x
o

5 6,78 cannot be prepared Williamson's Ether synthesis

by
 et
Lysoonato pyo
D Beat
CHzCHa Br DE_ yBEACH

µaso0Na city Br a Yadao CHL

CH
V CHS
d

2 Reaction of B x with dilute alkali

age x
RX R tg oHtNaX
n2seadyJNaHcoz.NaottkottiKzcoz.k
1h03
X Ct Br I Nazcoz Cacott

R 1929413 allyl
benzyl

a CHzCHzBr
aq KOH a CHzCH2OH

Ffg
so
fit
ii f
Br
l aq Kott
b M
6 d
X a

D D

c CH Br AV KOH a 0
Ho 1 CH

H H

IF
d Br ay Kot qpWott
CHz
city
Be
 oh
U
Ag Kott
p
e
M the

oet
CHz
s8

yy
NatOtto
f
Tcuz
SH
h it a
f
I
citz

f a CH3CH2OH
CHzatgott

Kmt

II.i
CHzatasa

CHzCH2B2 H HfCHzatasPh
CHzCHzOCH

CHzCH2scH3

t3 CHzCH20CH3

3 Finkelstein Reaction A halogenexchange method or reactor's

zoning XS Nato
pg I Nacl or NaBr

x Br U
Tune
EIT
Ppt in acetone

Mote of solvent
was is soluble in acetone while Wade NaBr are sparingly
soluble

in acetone

NaBrCNaI
solubility in acetone Nacl
 NAI NAB.r
a CHzcha Br
Acetone
CHEE
CHzCity 1

b
I't's mm
affine
EEnaBr
r
H H
me Nabr
zI
c NAI me
me By
Acetone
D D

Br F Nabr
d
fly
Nate
Acetone
f6 d
6 a

4 SwastjsRxn_ A halogenexchange method to prepare R F only

Coxsk
Bx Agf Critz DMSO
R R FEgfAgile
Sb SbX3
HgzFz
HgzXz

In DMSO Nucleophilic strength F0 do Bro I0

X Ct BHI
R 1920allylbenzyl

Agf
A CHzCH2BZ
DMSO
a CHzCH2 F
ftAgBr
t AyBr

CH3
A Agf
CH3
Agent
b I I
I
CH
CHA Cha Cha Br
DMSO HEHEHE
U
lat
d ata ata c if

FO
 Ea i Éy a
Aget

I Aged
d EE
f
A

Etf
U
e P Agt tycet
MY U Dmso d

t
Br

a
a
Ag't
DMSO
i
EEE a
BA
WWWF

me

5 and Kew with R X

Reaction of Agon

Ambident Nucleophile Nuo D

1 more then one donor site

if o iito
nato
EET betterdonor sitedueto c atom having
ionic
character
B x
n
Ay if ebetter
donor
more covalent
 NauvooKen Alkylnitrile
R EN
e
B x

Agan q N 8 Agxb i Alkylisonitrile

Similarly nanodor Knop Alkylnitrib

pro neo

BX o
Agnoz q NK
too
nitroalkane

6 Misc reaction

KNO2
CHzCHaONO

a
Saf
CHzCH2BT N2
a N0z
CHzCH2
to pyx

k h cHzCH2S Dh

NAL cHzCH21
Acetone

you Kon
pardon
b fX Br pas fBr

Br h
Yo kiEph
yawl Eigg
c Toy I I

d k cH3CH2Br
PAT ftp.SCHzCH
TsSCH2CH3
 I 413
7 Utz

f fat
jOp
e Br Cha k City City cited
µ a Br Cha d City City cH2SPh
I
CHz CHz

neoamyl neoamyl

CHz
city CHz
Br I It

ÉTÉ
f H
was
H D Acetone H D
City CHz

Br U F

Anth
Br
Agt et
8 AN Dmso

CHs
cuz cuz

ffy
f t Br F H
Ag a
H D HgFz Sbf H D
CH CH
CHz

Reaction with BOH

watch0 Sn2 not at0

R OH a X R I
b
strongerbasethen do
is
a ROH PIG R I Pods t Hel
U H U
Fil U f
R lo PLA
Mechi 12.0 H U Pf ee
race
Gte dow
sp
k
 b

a at
toffee fit PEE
Mets

Drivingforce is High B D E of 10 0 formed

f o
Il
Huta I Pods

Egs a H

me oet Pds U me Pods HI

D
SNZ
D

fpdott pas
Sna
gawd
d
Me me

oh 0 d POU T Hel
Snz

Quickstep
o o o
11 11 11 U
R R R C R c R c
I0 Io lo lO to Pdz
s f
H1 Rl H
R c R
t t t t t b
Rd 212cL Rood 212cal Rcodt RI POI

U Pelz d d H
similarly o
Il
R d ol R N
l l Hd
q c Nita et H

e
E if
 similarly o
Pds
gd H a B Caffe

r Er Ee cece

o d u
Pds
f

o
Pds a
E Lda

d
Meck
d Pd3
RcH
zf
U
If k cH
al