Chemical reactions of alkyl halide:
Nucleophilic substitution reaction:
Those organic compounds in which an sp3 hybridized carbon is bonded to an electronegative atom or group can undergo two type of reaction e.g. substitution reactions in which the electronegative atom or group is replaced by another atom or group. Sec
ond is elimination reaction in which the electronegative atom or group is eliminated along with hydrogen from an adjacent carbon. The electronegative atom or group which is substituted or eliminated is known as leaving group.
Because of more electronegativity of halogen atom it has partial negative charge and partial positive cha develops on carbon atom.
X = F, Cl, Br, I
Due to this polar carbon - halogen bond alkyl halides shows nucleophilic substitution and elimination reaction.
There are two important mechanisms for the substitution reaction
(1) A nucleophile is attracted to the partially positively charged carbon. As the nucleophile approaches the carbon,
it causes the carbon - halogen bond to break heterolytically (the halogen keeps both of the bonding electrons.)
(2) The carbon-halogen bond breaks heterolytically without any assistance from the nucleophile, by the help of polar protic solvent and carbocation is formed (solvolysis). Formed carbocation then reacts with the nucleophile to form the substitution product.
(A) Bimolecular nucleophilic substitution reaction (SN2)
The mechanism of SN2 reaction
Characteristic of SN2
(1) It is bimolecular, unistep process
(2) It is second order reaction because in the Rds two species are involved
(3) Kinetics of the reaction → rate ∝ [alkyl halide] [nucleophile]
rate ∝ k[alkyl halide] [nucleophile]
If the concentration of alkyl halide in the reaction mixture is doubled, the rate of the nucleophilic substitution reaction is double. If the concentration of nucleophile is doubled the rate of reaction is also double. If the concentration of both are doubled then the rate of the reaction quadriples.
(4) Energetics of the reaction →
Figure : A free energy diagrams for a hypothetical SN2 reaction that takes place with a negative DGº
(5) No intermediates are formed in the SN2 reaction, the reaction proceeds through the formation of an unstable arrangement of atoms or group called transition state.
(6) The stereochemistry of SN2 reaction → As we seen earlier, in an SN2 mechanism the nucleophile attacks from the back side, that is from the side directly opposite to the leaving group. this mode of attack causes a inversion of configuration at the carbon atom that is the target of nucleophilic attack. This inversion is also known as walden inversion.
(7) Factor's affecting the rate of SN2 reaction → Number of factors affect the relative rate of SN2 reaction, the most important factors are
(i) Structure of the substrate
(ii) Concentration and reactivity of the nucleophile
(iii) Effect of the solvent
(iv) Nature of the leaving group
(i) Effect of the structure of the substrate →
Order of reactivity in SN2 reaction : - CH3 > 1º > 2º >> 3º (unreactive)
the important factor behind this order of reactivity is a steric effect. Very large and bulky groups can often hinder the formation of the required transition state and crowding raises the energy of the transition state and slows down reaction.
Table : 6 Relative rates of reactions of alkyl halide in SN2 reaction.
(ii) According to kinetics of SN2 increasing the concentration of the nucleophile increases the rate of an SN2 reaction. The nature of nucleophile strongly affect the rate of SN2 reaction. A stronger nucleophile is much more effective than a weaker. For example we know that a negatively charged nucleophile is more reactive than its conjugate acid e.g. HO! > H2O, RO! > ROH.
Table : 7
Steric effects on nucleophilicity
t-butoxide ,Stronger base, nucleophile cannot approach the carbon atom so easily.
CH3 - CH2 - O!
ethoxide,weaker base, yet weaker yet stronger nucleophile
(iii) The effect of the solvent ° In polar protic solvent large nucleophiles are good, and the halide ions show the following order
I! > Br! > Cl! > F! (in polar protic solvent)
This effect is related to the strength of the interaction between nucleophile and solvent molecules of polar protic solvent forms hydrogen bond to nucleophiles in the following manner.
Because small nucleophile is solvated more by the polar protic solvent thus its nucleophilicity decreases and rate of SN2 decreases
Relative nucleophilicity in polar protic solvent
SH! > CN! > I! > OH! > N3! > Br! > ACO! > Cl! > F! > H2O
So, polar protic solvents are not useful for rate of SN2, if nucleophile is anionic. But polar aprotic solvent does not have any active hydrogen atom so they can not forms H bond with nucleophiles. Polar aprotic solvent have crowded positive centre, so they do not solvate the anion appreciably therefore the rate of SN2 reactions increased when they are carried out in polar aprotic solvent.
Examples of polar aprotic solvent.
In DMSO, the relative order of reactivity of halide ions is
F! > Cl! > Br! > I!
(iv) The nature of the leaving group ° The best leaving groups are those that become the most stable ion after they leave, because leaving group generally leave as a negative ion, so those leaving group are good, which stabilise negative charge most effectively and weak base do this best, so weaker bases are good leaving groups. A good leaving group always stabilize the transition state and lowers its free energy of activation and thereby increases the rate of the reaction.
Order of leaving ability of halide ion
I! > Br! > Cl! > F!
Other leaving groups are
Strongly basic ions rarely act as leaving group →
Table : 8 Examples of SN2 reactions of alkyl halide →
|Nucleophile||Product||Class of Product|
|R -||Alkyl halide|
|R -||Thioether (sulphide)|
|R - COO - R||Ester|
|[R - PPh3]+||Posphonium salt|
Ex. Complete the following reactions with mechanism
(c) Ph - CH2Cl
Sol. CH3-CH2-O! is present in excess and it is stronger nucleophile than Ph - O! so product is Ph-CH2 - OEt
(d) CH3 - C º CH X Y
(e) Ph3 → Salt
Ex. When the concentration of alkyl halide is tripled and the concentration of OH- ion is reduced to half, the rate of SN2 reaction increases by :
(A) 3 times (B) 2 times (C) 1.5 times (D) 6 times
Ex. In the given reaction, CH3CH2 - X CH3SNa °
The fastest reaction occurs when 'X' is -
(A) - OH (B) - F (C) - OCOCF3 (D) OCOCH3
Ex. Correct decreasing order of reactivity towards SN2 reaction
(III) CH3CH2CH2CH2 Cl
(A) IV > I > II > III (B) III > II > I > IV (C) IV > I > III > II (D) II > I > IV > III
Q.2 KF Products.
What is the function of 8 corwn-6?
Q.3 Write mechanisms that account for the product of the following reactions:
(b) NH2-CH2-CH2-CH 2-CH2-Br
Q.4 Draw a flscher projection for the product of the following SN2 reaction
(B) Unimolecular nucleophillic substitution reaction (SN1) :
Characteristics of SN1 reactions
1. It is unimolecular, two step process and intermediate is formed, (intermediate is carbocation)
2. It is first order reaction
3. Kinetics of the reaction
Rate ∝ [Alkyl halide]
Rate = k[(CH3)3C-X]
Rate of SN1 reaction is independent of concentration and reactivity of nucleophile.
4. Energetics of the SN1
Figure : free energy diagram for the SN1 reaction.
5 Factor's affecting the rates of SN1
5.(i) The structure of the substrate °
The Rds of the SN1 reaction is ionization step, in this step form a carbocation. This ionisation is strongly endothermic process, rate of SN1 reaction depends strongly on carbocation stability because carbocation is the intermediate of SN1 reaction which determines the energy of activation of the reaction.
SN1 reactivity : 3º > 2º > 1º > CH3 - X
5.(ii) Concentration and reactivity of the nucleophile °
The rate of SN1 reactions are unaffected by the concentration and nature of the nucleophile
5.(iii) Effect of the solvent ° the ioizing ability of the solvent:
Because to solvate cations and anions so effectively the use of polar protic solvent will greatly increase the rate of ionization of an alkyl halide in any SN1 reaction. It does this because solvation stabilizes the transition state leading to the intermediate carbocation and halide ion more than it does the reactant, thus the energy of activation is lower.
Table : 9 Dielectric constants (ä) and ionization rates of t-Butylchloride in common solvents
5.(iV) The nature of the leaving group °
In the SN1 reaction the leaving group begins to acquire a negative charge as the transition state is reached stabilisation of this developing negative charge at the leaving group stabilizes the transition state and : this lowers the free energy of activation and thereby increases the rate of reaction.
6. Stereochemistry of SN1 reactions → In the SN1 mechanism, the carbocation intermediate is sp2 hybridized and planar. A nucleophile can attack on the carbocation from either face,if reactant is chiral than after attack of nucleophile from both faces gives both enantiomers of the product, which is called recemization.
Mechanism of recemization (SN1) →
Comparison of SN1 and SN2 reactions :
Effect of the nucleophile
Nucleophile strength is not important
Stronger nucleophile is required
Effect of the substrate
3° > 2° > 1° > CH3X
CH3X > 1° >2°
Effect of solvent
Good ionizing solvent required
It goes faster in less polar solvent, if Nud is present
Rate = k [R-X]
Rate = k[R-X] [Nu°]
Ex. 6 Predict the compound in each pair that will undergo solvolysis (in aqueous ethanol) more rapidly.
Sol. (a) II > I (b) II > I (c) I > II (d) II > I (e) II > I
Ex. 7 Give the solvolysis products expected when each compound is heated in ethanol
Ex.8 The rate of SN1 reaction is fastest with
Reaction of RX with aq. KOH
1. R - OH + KCl
2. CH3-CH2-Cl CH3-CH2-OH
3. CH3-CH CH3-CH CH3-CHO
4. CH3-C CH3-C CH3COOH
5. C - C - C - C - Br C - C - C - C - OH
7. 14C = C - C - I 14C = C - C - OH + C = C - C14 - OH
Other Nucleophilic reaction of R - X :-
WillionSon's Ether Synthesis: (SN2)
2. EtONa + Me - Cl EtOMe
Rate (2) > (3) 2 is better method. (Due to less steric hindrence)
4. MeONa + PhCl No reaction
5. + NaCl
6. Me3CO!NaÅ + MeCl Me3COMe + NaCl
7. MeO!NaÅ + Me3C - Cl + MeOH + NaCl
8. PhONa + Me3C-Cl + PhOH + NaCl
9. Me3CONa + Ph-Cl No. reaction
Me3CO-Ph can not prepared by willionson's ether synthesis.
3. + HCl
4. + HBr
5. (Pyridinium salt)
Some Other reactions
Hydrolysis of Ether
2. MeOEt Et - + Me - OH
Reaction of ether with HI :
1. Me - O - Et
2. (Due to formation of more stable carbocation)
With moist and dry Ag2O :
2. 2Me - Cl Me - O - Me + 2AgCl
3. Me - Cl + EtCl Me - O - Et + Me - O - Me + EtOEt
SNi (Nucleophilic substitution intramolecular )
R - Cl + O = S = O (g)
Note : (1) In SNi retention of configuration takes place.
Note : (2) In presence of pyridene above reaction follow the SN2 reaction mechanism.
SNNGP(Neighbouring group participation)
Increase in rate of SN reaction due to attack of internal nucleophie is called as SNNGP is also known as Anchimeric assistence.
1. Internal nucleophile must be present
2. Internal nucleophile must be anti to lg.
During NGP :-
3. + (enantiomer) Rate 3 > 2 > 1