NUCLEOPHILIC UNI-BI MOLECULAR

REACTION(SN1 & SN2 REACTIONS)

PRESENTED BY
RESHMI PAUL
VP22PHAR0300002
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
GITAM DEEMED TO BE UNIVERSITY
VISHAKHAPATNAM
 CONTENT

NUCLEOPHILIC SUBSTITUTION REACTION

SN1 REACTION(INTRODUCTION)
FACTOR AFFECTING SN1 REACTION
REACTION AND REACTION MECHANISM
SN2 REACTION
FACTOR AFFECTING SN2 REACTION
REACTION AND REACTION MECHANISM
DIFFERENCE BETWEEN SN1 &SN2 REACTION
 NUCLEOPHILIC SUBSTITUTION REACTION

• Overall a nucleophilic substitution can be represented as follows:

Nu C LG LG
C Nu

• There are two fundamental events in a nucleophilic substitution reaction:

 formation of the new σ bond to the nucleophile

 breaking of the σ bond to the leaving group

• Depending on the relative timing of these events, three different mechanisms are possible:

 Bond breaking to form a carbocation proceeds the formation of the new bond: SN1 reaction

 Simultaneous bond formation and bond breaking: SN2 reaction

 SN1 REACTION(INTRODUCTION)

• The SN1 reaction is a substitution reaction in organic chemistry . “SN” stands for nucleophilic substitution and “1”
represents thst the rate determining step is unimolecular.

Substrate for SN1 reaction:

• Best if tertiary or conjugated (benzylic or allylic) carbocation can be formed as leaving group departs never primary

Formation of carbonium ion:

• Reactivity of an alkyl halide depends chiefly upon how stable a carbonium ion it can form. In SN1 reactions the order of
reactivity of alkyl halides is Allyl, benzyl >3 o>2o>1o>CH3X.

• 3oalkyl halides undergo SN1 reaction very fast because of the high stability of 30carbocations. S N1 reaction.
factors affecting the rates of SN1 reaction
Nucleophile character in SN1 reaction:

• Best if more reactive (i.e. more anionic or more basic)

Leaving Group nature:

• Best if more stable (i.e. can support negative charge well)

• Examples: TsO- (very good) > I-> Br-> Cl-> F-(poor)

Solvent used in SN1 reaction:

• Protic solvents used in SN1 reaction because formation of carbocation intermediate is the rate determining step.

Example : the reaction of tert- butyl bromide with sodium hydroxide in a mixture of water and acetone to form tert-butyl

alcohol is a good example for SN1 REACTION

Reaction and reaction mechanism
• General reaction- (CH3)3Br +2H2O Acetone (CH3)3COH

Mechanism- Step 1:
CH3 CH3

H3C C Br H3C C+ Br
+
CH3 CH3 bromide
Tert-Butyl bromide Carbocation
Step2:
CH3 CH3 H

H3C C + O H3 C C O

H H H
CH3 CH3

Carbocation Oxonium

CH3
CH3
Step3: H
+ O CH3 C OH + H3O
H3 C C O
H H
H CH3 Hydronium
CH3

Oxonium Water Tert-butyl alcohol

 SN 2 REACTION

• SN2 stands for substitution nucleophilic bimolecular reaction. In this reaction one bond is formed and one bond is broken in one step.

• In an SN2 reaction, Nucleophile attacks opposite side of the leaving group. This occurs because the nucleophilic attack is always on the back
lobe (antibonding orbital) of the carbon atom acting as the nucleus. The bond between nucleophile (Nu) and carbon (C) forms at the exact same
time that the bond between carbon and Leaving Group(L) breaks. In other words, Nu-C bond formation and C-Leaving Group bond breakage
happen simultaneously. In the transition state, the carbon is partially attached to both.

• Factors affecting the rates of SN2 reaction

1) Structure of substrate-

 In SN2 reaction the substrate plays the most important part in determining the rate of the reaction.

 This is because the nucleophile attacks from the back of the substrate, thus breaking the carbon leaving group bond and forming the carbon
nucleophile bond. Therefore, to maximise the rate of the SN2 reaction, the back of the substrate must be as unhindered as possible.

 Overall, this means that methyl and primary substrates react the fastest, followed by secondary substrates.Tertiary substrates do not participate
in SN2 reactions, because of steric hindrance.
Cont….
2) The nature of nucleophile-

 A nucleophile with a negative charge is always more powerful than its conjugate acid. Thus OH¯ is more powerful than H2O, NH2¯ is more

powerful than NH3, CH3O¯ is more powerful than CH3OH, etc.

 In comparing nucleophiles whose attacking atom is in the same row of the periodic table, nucleophilicity isapproximately in order of basicity as

following:

NH2¯> RO¯ > OH¯> NH3 > F¯> H2O

 Going down the periodic table, nucleophilicity increases, though basicity decreases. Thus the usual order of halide nucleophilicity is:

I¯ > Br¯ > Cl¯ > F¯

 So, a strong/anionic nucleophile always favors SN2 manner of nucleophilic substitution.

3)Effect of solvent-

Polar aprotic solvent (without OH) favors SN2.

- For examples of polar aprotic solvents are acetone, dimethylsulfoxide, N,N’-dimethylformamide, etc.
Rection and reaction mechanism

• General Reaction-
CH3BR + OH CH3OH + Br

Mechanism-

H
H
OH C Br HO C + Br
HO + C Br

H
 Difference between SN1 and SN2
Points S N1 S N2
Steps Two steps One steps

molecularity unimolecular bimolecular

Kinetics and rate First order Second order

stereochemistry racemization Complete inversion

Effect of substrate Stability of carbocation: Steric hindrance decreases the rate of reaction:
tertiary>secondary>primary>methyl Methyl> primary >secondary> tertiary

Effects of solvents on rate Polar protic solvents like water favors S N1. Polar aprotic solvents like acetone favors S N2.

Nucleophilicity and concentration of Weak nucleophiles of low concentration can Strong nucleophiles of high concentration
nucleophiles make the reaction to occur increases the rate

Leaving group effect Weakly basic and highly polarizable group Weakly basic and highly polarizable group
increases the rate increases the rate

Reaction intermediate carbocation none

Competition reaction E1 E2
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