Nucleophilic Substitution Reactions
(Halogen Exchange Reaction)
Definition of SN Reactions
The substitution reactions in which
one nucleophile displaces another nucleophile (–X) from electrophilic carbon of
a compound are called Nucleophilic Substitution Reactions or SN reactions
[where S stands for substitution and N for nucleophilic]. These reactions occur
in alkyl halides. There are two types of SN Reactions
General Representation
Examples of Nucleophiles
Nu– = OH–, OR–, SH–, SR–, CN–, NH2–,–NHR, >NR2, –NR3, RCOO–, NO2–, etc.
Explanation
The reactivity of alkyl halide is due to the polarity of C–X bond. Since the halogen atom is more electronegative than carbon atom, therefore carbon atom attached to halogen atom carries a partial positive charge i.e. it becomes electrophilic in nature while halogen atom develops a partial negative charge i.e. it becomes nucleophilic in nature. The electrophilic a-carbon atom of alkyl halide has a tendency to accept an electron pair from a nucleophilic reagent and forms a new carbon-nucleophile bond while in doing so old C–X bond breaks giving X– ion. It involves heterolytic cleavage. [The reaction occurs in solution and the function of solvent is to stabilize the ion]. The reagent Nu– is called Attacking Nucleophile, alkyl halide (R–CH2–X) is called Substrate and halide (X–) ion is called Leaving Nucleophile.
The attacking nucleophile should be a stronger base than the leaving X– group in a SN reaction e.g. OH– group displaces weaker base Cl– but the reverse is not true.
Difference between SN2 and SN1 Reactions
Bimolecular Nucleophilic Substitution (SN2) Reaction
Definition
of Bimolecular Nucleophilic Substitution (SN2) Reaction
The single step SN reaction
characterized by back-side displacement with inversion of configuration of
α-carbon (Walden Inversion) marked by transition state involving the
formation of the carbon-nucleophile bond and the cleavage of carbon-halogen
bond simultaneously and the reaction rate is influenced by both the concentrations of
substrate alkyl halide and attacking nucleophile is known as Bimolecular
Nucleophilic Substitution (SN2) Reaction.
Mechanism
and General Representation of Bimolecular Nucleophilic Substitution (SN2) Reaction
In SN2 reaction, the removal of outgoing nucleophile (–X) and new entrant nucleophile take place simultaneously. Stated differently, attacking nucleophile (Nu‒) becomes partially attached to the electrophilic carbon of alkyl halides as well as the halide group (X-) is detached at the same time. This momentary unstable high-energy state is termed as transition state which readily changes to new carbon-nucleophile bond leaving halide group as nucleophile.
As the bond formation and bond cleavage processes occur simultaneously, it is also the “rate-determining or slow step” that determines the overall reaction rate. Since two molecules undergo change in covalency in the rate-determining step of reaction, therefore, one-step nucleophilic substitution reaction is bimolecular reaction symbolized as SN2which stands for bimolecular nucleophilic substitution reactions. In SN2 reaction, the attacking nucleophile always comes from the side opposite to that from which the halide ion is attached.
In transition state of SN2 mechanism, the carbon atom is sp2-hybridized due to its planar structure. At this point, carbon almost acquires ‘Pentavalency’ with three full bonds and two partial bonds, and a planar complex is formed, which is sp2-hybridized.
Details of Mechanism (Hughes, Ingold, Walden)
Walden
Inversion
There
are two possible spatial arrangements of the new entrant nucleophile in relation to
the outgoing leaving nucleophile. The first stereochemical possibility is
termed as “front-side substitution” with retention of configuration in which attacking nucleophile
simply assumes the position of occupied by the leaving group i.e. it attacks
the substrate at the same face from which leaving group departs. The second
stereochemical possibility is called “back-side substitution” with inversion of
configuration
in which attacking nucleophile attacks the substrate from the side opposite the
bond to the leaving group.
It has
been found through numerous experiments by Hughes, Ingold, Walden, that SN2 mechanism is stereospecific and proceeds with inversion of
configuration of α-carbon. There is a stereoelectronic requirement for the nucleophile to
approach α-carbon from the side opposite the bond to the leaving group. This
back-side displacement with inversion of configuration is often termed as Walden Inversion.
In order to give to the nucleophile enough
room to attack, the substrate carbon atom changes its state of
hybridization from tetrahedral sp3
to planar sp2.
Steric
Hindrance
In SN2 mechanism, the attacking nucleophile approaches the alkyl halides from the side opposite to that of the halide group. Alkyl groups being larger than hydrogen atoms, occupy more space. Hence if alkyl groups are present on the α-carbon of the C – X bond, they block the entry of the attacking nucleophile. The blocking of new entrant nucleophile on α-carbon of substrate due to presence of bulky alkyl groups on α-carbon (or β-carbon ) is known as steric hindrance (steric = space).
The steric hindrance increases from 1° to 3°-alkyl halides due to increase in number of alkyl groups from 0 or 1 to 2 and 3 and tendency for SN2 reaction decreases in the same order.
The steric hindrance shields the α-carbon from back-side attack of nucleophile thereby favouring SN1 mechanism instead of SN2. Thus tertiary alkyl halides with greater steric hindrance due to most crowded alkyl substituents structure are least reactive for SN2 reactions.
Examples of Alkyl Halides undergoing SN2Reactions
Order of reactivity of different alkyl halides for SN2reaction is 1°-alkyl halides > 2°-alkyl halides > 3°-alkyl halides. Steric hindrance in tertiary alkyl halides shields the from back-side nucleophilic attack. Thus tertiary alkyl halides with greater steric hindrance due to most crowded alkyl substituents structure are least reactive for SN2reactions.
SN2reactions occur in primary alkyl halides (CH3X or
RCH2X) due to least steric hindrance and least stability of their
carbonium ions (RCH2+).
Factors Favouring SN2Reactions
Polar aprotic solvents (DMSO, acetone, acetonitrile, DMF, HMPA; Hexamethylphosphoramide) which reduces ionization, favour SN2 mechanism. Aprotic solvents that lacks – OH group with low dielectric constants [such as dimethyl sulphoxide, (CH3)2S=O (48.9), methyl nitrile, CH3C≡N (37.5)] and less tendency to solvate attacking nucleophile, leaving them much more able to express their nucleophilicity, favours SN2 reactions.
Kinetics
The rate of SN2 reaction depends upon the concentration of both the attacking nucleophile and substrate (alkyl halide). The rate expression according to law of mas action is:
Unimolecular Nucleophilic Substitution (SN1) Reaction
Definition of Unimolecular Nucleophilic Substitution (SN1) Reaction
The two steps SN reaction characterized by either-side displacement with 50% inversion and 50% retention of configuration of α-carbon marked by slow reversible heterolytic cleavage or ionization of C-X bond of alkyl halide into carbonium ion and halide ion followed by fast combination of carbonium ion with attacking nucleophile and the reaction rate is influenced by the concentration of substrate (alkyl halide) only is known as Unimolecular Nucleophilic Substitution (SN1) Reaction.
Mechanism and General Representation of Bimolecular Nucleophilic
Substitution (SN1) Reaction
SN1 reaction proceeds through two steps mechanism. The first step
involves the slow reversible Heterolytic fission of C – X bond of alkyl halide
into carbonium ion (R+) and halide ion (X-) while second
step involves the fast combination of carbonium ion and attacking nucleophile
to form the final product.
The C –
X bond cleavage step is slow and hence rate-determining step in which only one
molecule i.e. alkyl halide undergoes change in covalency, therefore, the two
steps SN reaction is unimolecular reaction symbolized as SN1 reaction which stands
for unimolecular nucleophilic substitution reactions.
inversion product will be present in higher amount than
retention product.
Examples of Alkyl Halides
undergoing SN1 Reactions
Order of reactivity of different alkyl halides for SN1 reactions is 3°-alkyl halides > 2°-alkyl halides > 1°-alkyl halides. SN1 reactions occur in
tertiary alkyl halides (R3CX) due to stability of tertiary carbonium
ions (R3C+) and greater steric hindrance.
Factors Favouring SN1Reactions
Polar protic solvents which help ionization favour SN1 mechanism.
Kinetics
The rate of SN1 reactions depend on the concentration of substrate (alkyl halides) only and is independent of concentration of attacking nucleophile. The rate-expression according to law of mass action is:
No comments:
Post a Comment