nucleophilic substitution reaction (sn2)-1

19
Nucleophilic substitution bimolecular (S N 2) Reaction Prof. R. B. Sunoj IIT Bombay

Upload: ramesh-katkam

Post on 29-Oct-2014

82 views

Category:

Documents


4 download

TRANSCRIPT

Page 1: Nucleophilic Substitution Reaction (SN2)-1

Nucleophilic substitution bimolecular (SN2) Reaction

Prof. R. B. SunojIIT Bombay

Page 2: Nucleophilic Substitution Reaction (SN2)-1

SN2 correspond to substitution Nucleophilic Bimolecular.

This Reaction is a concerted reaction in which bond forming and bond

breaking occur simultaneously.

Figure –SN2 reaction

Energy required to break the bond is compensated by bond

formation.

Introduction

Page 3: Nucleophilic Substitution Reaction (SN2)-1

Example 1:

Introduction

Example 2:

Example 3:

Page 4: Nucleophilic Substitution Reaction (SN2)-1

Kinetics The rate of the reaction is found to be vary linearly with non zero slope with

respect to electrophile as well as nucleophile .

2 in the SN2 correspond to bimolecular.

In presence of large excess of nucleophile kinetics is found to be first

order experimentally even though mechanism is bimolecular.

Nucleophile affect the rate even being in large excess but concentration does

not vary significantly and rate is found to be determined alone by electrophile.

Such kinetics are known as “Pseudo first order reaction”.

Rate=K [elec][Nucl] K= equilibrium constant

rate=K[elec]

Page 5: Nucleophilic Substitution Reaction (SN2)-1

Mechanism During SN2 reaction nucleophile first approaches to antibonding orbital of

C-Y bond.

Attractive interaction between orbital, develop bond between incoming

group and carbon. Simultaneously the leaving group start to depart away

from carbon center.

Substitution may be possible either via front side or backside attack of

nucleophile.

In SN2 substitution backside attack is preferred in which approach of

nucleophile is 180 away from the leaving group.⁰

Page 6: Nucleophilic Substitution Reaction (SN2)-1

Walden Inversion Complete Inversion in stereochemistry is observed during aliphatic

nucleophilic substitution via SN2 pathway, confirming that backside

attack is preferred over front side attack.

Stereochemical outcome of the SN2 reaction is termed as Walden

inversion in honor of his discovery.

Only backside attack of nucleophile provide the most favorable interaction

between antibonding orbital of C-Y bond and orbital of incoming nucleophile.

Page 7: Nucleophilic Substitution Reaction (SN2)-1

Nucleophile and Nucleofuge Nucleophile is a species looking for a nucleus (positive charge) to which it

can donate its electron.

Usually nucleophiles are electron rich species.

A Nucleofuge is nucleophile departing from a molecule instead of adding.

The term Nucleophile and Nucleofuge are kinetic term, used for

discussing reactivity and kinetics.

Page 8: Nucleophilic Substitution Reaction (SN2)-1

Effect of Solvent Solvent may play a vital role in the rate of SN2 reaction as it involves either

creation or dispersion of charge.

Charged species are more stabilized in the polar solvent than non-polar

solvent.

Difference between the solvation capacity of reactant and transition state in

various solvent lead to the solvent effect in a reaction.

Reactants Transition State Charge Creation/Dispersion

Effect of Increasing the

Polarity of Solvent

Charge dispersion Retard the reaction

Charge creation speed the reaction

Charge dispersion Retard the reaction

Charge dispersion Retard the reaction

δδNuc R-LG

Nuc R LGNuc R-LG

Nuc R LG

δ

δ δ

Nuc R-LGδδ

Nuc R-LG

Nuc R LG

Nuc R LGδ

Page 9: Nucleophilic Substitution Reaction (SN2)-1

In case of negative nucleophile a remarkable change in rate of SN2 reaction

is observed while changing the solvent from polar protic to polar non-protic

solvent.

In polar aprotic solvent negatively charged nucleophile are less soluble but

solvent are polar enough to solubilize the nucleophile making them highly

reactive. Solvent K relative

Methanol 0.9

Water 1.0

Formamide 14.1

Acetonitrile 3.58 x 104

Acetone 1.41 x 106

Solubility of nucleophile is a major problem in substitution reaction,

particularly in less polar aprotic solvent.

Crown ether is added to solvate the counter-cation which induce the solubility

of corresponding anionic nucleophile.

Page 10: Nucleophilic Substitution Reaction (SN2)-1

Structure Function Correlation With Nucleophile

In SN2 reaction stronger the nucleophile faster the reaction will occur.

Strength of a nucleophile can be determined by given principle-

1. A nucleophile with negative charge is more powerful than its conjugate acid.

Example: NH2─ >NH3, OH─ >H2O,

2. Nucleophilicity is almost in same order as basicity in row.

Example: R3C ─ > R2N ─ > RO ─ > F ─

NH2 ─ > RO ─ >R2NH ─ > ArO ─ > NH3 > Pyridine > F ─ > H2O > ClO4

3. Going down in a group nucleophilicity increase while basicity decrease.

Example: I ─ >Br ─ > Cl ─ > F ─(less solvation, Higher polarization)

S ─ >O ─

Page 11: Nucleophilic Substitution Reaction (SN2)-1

4. More free nucleophile, more nucleophilicity.

Example 1: Rate of reaction using NaOH can be largely enhanced by

specifically solvating cation Na+. (use of crown ether).

Example 2: NaOHDMSO >NaOHwater (basicity)

In water Na+ and HO ─ both are solvated while in DMSO

Na+ is solvated preferably than HO ─ leaving HO ─ as free

nucleophile.

Structure Function Correlation With Nucleophile

Page 12: Nucleophilic Substitution Reaction (SN2)-1

Structure function correlation with leaving group Negative charge develops on leaving group during the rate determining step.

Thus, reaction proceed faster with a leaving group which stabilize better

negative charge.

Better leaving group are mostly weak bases which stabilize the negative

charges.

Example: TsO ─ , MsO ─, TfO ─

In presence of better leaving group, SN1 reaction do not require strong base,

but for SN2 reaction it is required.

Example:

1. XH is always a weaker base than X ─. Thus XH is a better leaving group which

facilitate the SN2 reaction.

HS─ > H2S, HO ─ > H2O, I ─ > HI, NH2 ─ >NH3

2. Acidic medium also protonate the base making them weaker.

ROH is converted to ROH2+ in acid medium which is a better leaving group.

Page 13: Nucleophilic Substitution Reaction (SN2)-1

Structure Function Correlation With R Group R group plays vital role on the rate of reaction as well as in determination of the

reaction.

R group may have stearic, electronic and neighboring group effect.

Stearic hindrance may slower the rate of reaction, as nucleophile adds to the

carbon centre in rate determining step.

During transition state incoming nucleophile(Nuc) and leaving group(LG) are

90 to the R group. Thus placing larger group at 90 to LG and Nuc, transition ⁰ ⁰

state will be more strained which causes lesser rate of reaction.

R

R

YX

R

900900

Bulkier R group increase steric hindrance

Page 14: Nucleophilic Substitution Reaction (SN2)-1

A bulkier adjacent group may bend the trajectory of nucleophile away from

the linear approach which leads to a strained transition state.

RRR

RR

LGNuc

Strained transition state due to adjacent group steric effect

electron withdrawing nature of groups having sp2 carbon(vinyl and phenyl)

make the adjacent carbon more electrophilic and hence reactivity towards

nucleophile increases.

Example:

Higher rate for nucleophilic substitution at allyl and benzyl system.

Structure Function Correlation With R Group

Page 15: Nucleophilic Substitution Reaction (SN2)-1

Neighboring Group Participation

Two consecutive SN2 substitution, leads to retention of

configuration.

In presence of electron donor neighboring group, reaction undergo with higher

rate of reaction than expected and neither inversion nor racemisation is

observed.

It shows the neighboring group participation in the reaction.

Example 1

Page 16: Nucleophilic Substitution Reaction (SN2)-1

The most likely neighboring group participation in three, five, six

membered ring.

Four membered ring neighboring group participation is higher in case

of alkyl substitution on α or β carbon.

The effect of halogen increase as going down the group ( I> Br> Cl ).

Neighboring Group ParticipationExample 2

Page 17: Nucleophilic Substitution Reaction (SN2)-1

Some neighboring groups are COO ─, COOR, COAr, OCOR, OR, OH, O─,

NH2 , NHR , NHCOR, SH, SR, I, Br, S ─

Example 3

Example 4

Page 18: Nucleophilic Substitution Reaction (SN2)-1

SN2’ Reaction

allylic rearrangement in SN2 condition is known as SN2’ reaction.

X

Usual attack(SN2)SN2' attack

Attack at γ carbon with SN2 condition is SN2’ reaction.

Simultaneous movement of three electron pair during transition state

Page 19: Nucleophilic Substitution Reaction (SN2)-1

Increasing the size of nucleophile as well as stearic hindrance at α- carbon

increases the extent of SN2 reaction.

Leaving group also affect the extent of reaction in certain cases.

Example:

PhCH=CHCH2X treated with LiAlH4 when X=Br,Cl only SN2 reaction

=P(Ph)3+Br ─ only SN2’ reaction

Stereochemistry depends upon the nature of incoming group and leaving group

in SN2’ reaction, still syn-substitution is preferred over anti.

SN2’ Reaction