SN1, SN2, and SNi mechanisms DR K RAJARAJAN
1
SN2 Reaction Mechanism
SN1 Reaction Mechanism
SNi Reaction Mechanism
DR. K. RAJARAJAN
ASSISTANT PROF. OF CHEMISTRY
RAJAH SERFOJI GOVT. COLLEGE
THANJAVUR 613 005
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
2
SN2 Reaction Mechanism
The SN2 reaction is a nucleophilic substitution reaction where a bond is broken and another is formed synchronously. Two reacting species are involved in the rate determining step of the reaction. The term ‘SN2’ stands for – Substitution Nucleophilic Bimolecular. This type of reaction is also referred to as bimolecular nucleophilic substitution, associative substitution, and interchange mechanism.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
3
Examples of SN2 Reactions
The reaction between 2-bromobutane and OH- (nucleophile from KOH)
The reaction between methyl chloride and nucleophile OH-
The reaction between methyl chloride and bromide ion.
The reaction between benzyl bromide and sodium cyanide
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
4
This reaction proceeds through a backside attack by the nucleophile on the substrate. The nucleophile approaches the given substrate at an angle of 180 degree to the carbon-leaving group bond. The carbon-nucleophile bond forms and carbon-leaving group bond breaks simultaneously through a transition state.
The SN2 reaction mechanism for the nucleophilic substitution of chloroethane with bromine acting as the nucleophile
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
5
Now, the leaving group is pushed out of the transition state on the opposite side of the carbon-nucleophile bond, forming the required product. It is important to note that the product is formed with an inversion of the tetrahedral geometry at the atom in the centre. The rate of the SN2 mechanism depends both of the concentrations of substrate and attacking nucleophile.
Rate = K [SUBSTRATE] [NUCLEOPHILE]
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
6
SN1 Reaction Mechanism
The SN1 reaction is a nucleophilic substitution reaction where the rate-determining step is unimolecular. It is a type of organic substitution reaction. SN1 stands for substitution nucleophilic unimolecular. This reaction involves the formation of a carbocation intermediate. The hydrolysis of tertiary butyl bromide as an example, the mechanism of the SN1 reaction can be understood via the following steps.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
7
The nucleophile is not involved in the initial step of rate-determination, thus the concentration does not affect the overall reaction rate. This reaction follows first order kinetics. The reaction is first order with respect to alkyl halide while zero order with respect to the nucleophile
Rate = k [Substrate]
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
8
Step 1 The mechanism of the SN1 reaction
The carbon-bromine bond is a polar covalent bond. The cleavage of this bond allows the removal of the leaving group (bromide ion).
When the bromide ion leaves the tertiary butyl bromide, a carbocation intermediate is formed.
This is the rate-determining step of the SN1 mechanism.
It is important to note that the breaking of the carbon-bromine bond is endothermic.
hydrolysis of tertiary butyl bromide
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
9
Step 2 The mechanism of the SN1 reaction
In the second step of the SN1 reaction mechanism, the carbocation is attacked by the nucleophile.
Since water is used as a solvent, an oxonium ion intermediate is formed.
Since the solvent is of a neutral nature, a third step where deprotonation occurs is necessary.
hydrolysis of tertiary butyl bromide
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
10
Step 3 The mechanism of the SN1 reaction
The positive charge on the carbocation was shifted to the oxygen in the previous step.
The water solvent now acts as a base and deprotonates the oxonium ion to yield the required alcohol along with a hydronium ion as the product.
Step 2 and Step 3 of this reaction are fast.
hydrolysis of tertiary butyl bromide
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
11
SNi Reaction
SNi stands for substitution, nucleophilic internal. The reaction between
alcohols and thionyl chloride has been studied extensively.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
12
The product chloride is formed with complete retention of configuration on the starting alcohol. The reaction proceeds with the formation of a chlorosulphite ester which collapses with elimination on SO2. The chlorosulphite ester could form the product by SN2 with inversion; SN1 with racemization. In the present case, there occurs total retention of configuration identity,
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
13
Meachanism of SNi
Step-I: The first step is formation of cholrosulphite ester (intermediate)
Step-II: Dissociation of the chorosulphite ester to form an ion- pair (not dissociated ions)
Step-III: Because of the geometry of the ion pair, the chlorine atom is forced to attach the carbonium ion from the same side as original C-O bond of the alcohol (internal attack)
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
14
Factors Influencing SN2 Reaction
Effect of Solvent
Nucleophiles are more stabilized than the transition state in polar protic solvents due to solvation where the ground state energy of nucleophile is reduced in comparison to the transition state's energy. Due to this, reaction progress leads to a higher activation energy and thus to a lower reaction rate. The nucleophiles are less solvated in polar aprotic solvents (DMSO, DMF and HMPT) which results in the less stabilized ground state when compared to the polar protic solvents.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
15
Thus, the nucleophile is more reactive which leads to the lowering of activation energy, and a higher rate of the reaction. Thus, for SN2 mechanism, increasing solvent polarity usually decreases the rate of reaction.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
16
Effect of Leaving Group
A leaving group which becomes a more stable species after it departs is a better leaving group. The best leaving groups are the weakest bases. Stable anions are good leaving groups which results in the lowering of activation energy while reaction rate is higher.
For example, iodide anions are better leaving groups than chloride anions. Hydroxide anions, alkoxides, fluoride anions, and amide anions are poor leaving groups.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
17
Where, MsO‒ and TsO‒ are extremely good leaving groups due to resonance stabilization. Thus, the nature of leaving group not only affect the rate of reaction but may also change the reaction mechanism.
the leaving groups can be arranged in the order:
MsO‒, TsO‒ > I‒ > Br‒ > Cl‒ > F‒ > (‒OH, ‒NH2)
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
18
Factors Influencing SN1 Reaction
Effect of Solvent
Solvation of the carbocation allows the carbocation to be surrounded by more electron density, making the positive charge more stable. The solvent can be protic or aprotic, but it must be polar solvent. Polar protic solvents have a H-atom attached to an electronegative atom so the hydrogen is highly polarized. Polar aprotic solvents have a dipole moment, but their hydrogen is not highly polarized.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
19
Polar aprotic solvents are not used in SN1 reactions because some of them can react with the carbocation intermediate and lead to unwanted product. Thus, polar protic solvents are preferred in SN1 reaction which helps to speed up the rate of reaction due to large dipole moment of the solvent which helps to stabilize the transition state. The highly positive and highly negative parts interact with the substrate to lower the energy of the transition state. Since the carbocation is unstable, anything that can stabilize this even a little will speed up the reaction.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
20
Sometimes in an SN1 reaction the solvent acts as the nucleophile known as solvolysis reaction. The polarity and the ability of the solvent to stabilize the intermediate carbocation, is very important for the solvolysis. The dielectric constant of a solvent provides a measure of the solvent's polarity. A dielectric constant below 15 is usually considered non-polar. Thus, higher the dielectric constant more polar will be substance and in the case of SN1 reactions the faster the rate.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
21
Effect of Leaving Group
The leaving group is almost always expelled with a full negative charge. The best leaving groups are those that can best stabilize an anion (i.e. a weak base). SN1 reaction speeds up with a good leaving group. This is because the leaving group is involved in the rate-determining step. A good leaving group wants to leave so it breaks the C-leaving group bond faster.
, NH3 > H2O ≈ I- , Br- > Cl- > F- (-OH, -NH2)
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
22
From left to right on the periodic table, electron donating ability decreases and thus ability to be a good leaving group increases. Halides are an example of a good leaving group whose leaving-group ability increases as you go down the column. Other examples of good leaving group viz. methyl sulfate ion and other sulfonate ions.
(Good)….. I- > Br- > Cl- > F- …..(poor)
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
23
Thermodynamically also, anchimeric assistance is favored as the reaction between the substrate and Y- involves a large decrease in entropy of activation (∆S†), as the reactants are far less free in the transition state than before. Reaction of Z involves a much smaller loss of entropy.
SN1, SN2, and SNi mechanisms DR K RAJARAJAN
24