substituition nucleophilic unimolecular) · compounds undergo faster sn2 mechanism instead of sn1....
TRANSCRIPT
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SUBSTITUTION NUCLEOPHILIC REACTION
SN1: (Substituition Nucleophilic Unimolecular)
The reaction occure through these 2 steps. In the 1st step
leaving group liberates from the substrate (t-butyl bromide)
to form stable carbocation. This is the slowest (RATE
DETERMINING STEP). This is an endothermic process. In the
2nd step nucleophile (hydroxide ion) attack to the
carbocation. This is an exothermic process.
RATE = k [RX] (where, k= rate constant of slow step)
The energy profile diagram is given below.
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In the 1st step tetrahedral substrate (sp3 hybridized)
undergoes slow dissociation & form trigonal planar
carbocation (sp2 hybridized). P-orbilal of the carbocation is
vacant & perpendicular with respect to 3 sp2 hybridized
molecular orbital. Nucleophile can attack to carbocation (due
to planarity) from either side with equal possibility. So if SN1
reaction is carried out with any optically active chiral
substrate, after completing the reaction a mixture of equal
amounts of 2 enantiomers i.e. racemic mixture are obtained.
FACTORS EFFECTING SN1 REACTION:
Factors which influence the rate of SN1 reaction are given
below--
NATURE OF SUBSTRATES: Electrical effect influences the
rate of this reaction mechanism. The driving force of SN1
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reaction is the formation of stable carbocation. Mesomeric
(+M) effect, & hyperconjugation (+H) effect, indictive (+I)
effect make carbocation stable. So in SN1 reaction the
reactivity order of alkyl helices is 3°>2°>1°>Methyl cation.
Steric effect is less important in SN1 reaction since in R.D.S
steric strain reliefs due to structural change of tetrahedral
(bond angle 109.4°) to trigonal planar (bond angle 120°).
NATURE OF SOLVENT: Since on going from substrate to
R.D.S step charges generate due to formation of carbocation
& anion from neutral molecule SN1 reaction favours in polar
protic solvent.
Ionizing power of the solvent depends on dielectric constant
of the solvent & ability to sulfate ions. Higher the dielectric
constant, greater will be the polarity of solvent, higher will be
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the salvation through dipole-dipole interaction. Polar protic
solvents ( MeOH, EtOH, H2O etc.) Effectively solvate both the
cation & anion. The lone pair of the oxygen atom of H2O is
donated to vacant p orbital of the carbocation to make it
solvate. Anion solvated thorough H-bonding with water
molecules.
NATURE OF NUCLEOPHILIC: The rate of SN1 reaction doesn’t
depend on nature of nucleophile. Rate will be unchanged in
strong as well as weak nucleophile.
NATURE OF LEAVING GROUP: Rate of SN1 & SN2 reaction is
influenced by nature of leaving group. A group which is very
stable as an ion or neutral molecule, is a very good leaving
group. Lower the basicity higher the nucleophilicity.
In periodic table down the group the size of halogen
increases. So the C-X bond strength order is C-F>C-Cl> C-
Br>C-I due to size mismatch of C & X. So order of ability of
leaving group is I>Br>Cl>F.
SN2: (Substitution Nucleophilic Bimolecular)
This is aa single step concerted reaction. The approaching of
nucleophilicity & liberating the leaving group occure
simultaneously in one step. Nucleophile approaches to the
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opposite side with respect to the leaving group. So only one
product is obtained with inversion of stereochemistry when a
chiral molecule is taken as a substrate. The rate of the
reaction depends on both substrate concentration as well as
concentration of nucleophile.
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RATE = k [RX] [Nucleophile]
FACTORS EFFECTING SN2 REACTION:
Factors which influence the rate of SN2 reation are given
below—
NATURE OF SUBSTRATE: Both bond making with nucleophile
& bond breaking with leaving group of substrate occurs
simultaneously in the transition state of SN2 reaction
mechanism. So steric effect of the substrate highly influences
the rate of reaction. Higher will be bulkiness of the substrate,
lesser will be the attaking tendency of a nucleophile. Steric
hindrance increases in the order 3°>>>2°>1°>methyl. So the
order of rate of the is methyl>1°>2°>>>3°.
The electrical effect of substrate is not so much influenced
the reaction rate since in transition state the central carbon
of substrate is considerably more positive or negative
compared to initial molecule.
NATURE OF THE SOLVENT: The polarity of solvent doesn’t
effect considerably on the rate of the reaction. In the
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transition state the charge is dispersed. So rate of the
reaction increases in aprotic polar solvent (DMSO, DMF, DMA
etc.) These solvents preferentially solvate the cation of the
nucleophile & make anion free to attack readily to the
substrate.
NATURE OF THE NUCLEOPHILE: The nucleophilic power of
nucleophile highly effects on the rate of the reaction since in
the transition state nucleophile is involved. Stronger the
nucleophile higher will be the rate of the reaction. Among
water & hydroxide ion more nucleophilic is hydroxide ion due
to high charge density (charge/size). In aprotic solvent cation
is solvated & anion remains free. So anion having high charge
density will be a better nucleophile. So in DMSO the order of
nucleophilicity of helices is fluoride>chloride >bromide
>iodide.
FEW EXAMPLES OF SN1 & SN2 REACTIONS:
Reaction with benzylic substrate—
The carbocation formed at benzylic position is stabilised due
to (+M) effect of benzene ring. So Benzyl chloride undergo
SN1 reaction & undergo hydrolysis readily. So SN1 reaction is
more favorable compared to SN2. As the number of Ph ring
increases, stability carbocation increases due to increase
charge delocalisation & rate of the SN1 reaction increases.
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Order of rate of SN1 reaction—Ph3CBr >Ph2CHBr > PhCH2Br
Reaction With Bicyclic Compound—
According to Bredt's rule carbocation at bridgehead position
is highly unstable. So this compound is underactive towards
SN1 reaction & also underactive towards SN2 mechanism.
When Nucleophile will approache from the backside it will
face steric hindrance due to cage like structure.
Reaction With Epoxide--
In acidic condition at 1st oxygen will be protonated & due to
strain in 3 membered ring, ring opening takes place to form
more stable carbocation. After that nucleophile will attack
that carbocation to form product. So under acid catalytic
condition epoxide undergoes SN1 reaction.
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Under basic condition, nucleophile attack at the less
hindered position i.e. ring opening takes place at the less
hindered position. So SN2 reaction takes place.
Reaction with ether—
In the above reaction after liberating the leaving group
chloride ion the resulting carbocation is stabilised due to
(+M) effect of OMe group. Therefore it will undergo SN1
mechanism instead of SN2.
In the 1st step ether oxygen atom is protonated. After that
the O-CMe3 bond will be cleaved due to formation of most
stable 3° carbocation. Therefore when ether contains tertiary
alkyl group then undergoes SN1 mechanism. Later iodide ion
will attack as a nucleophile.
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But when ether contains primary alkyl group instead of
tertiary one, it will undergo SN2 mechanism to the less
crowded alkyl group.
With Alpha-Halo Carbonyl Compounds—
Due to (-I) & (-M) effect of carbonyl group the positive sign
on the alpha carbon atom is unstable. So alpha halo carbonyl
Compounds undergo faster SN2 mechanism instead of SN1.
SNi : (Intramolecular Nucleophilic Substitution)
The solvent used in SNi mechanism is Tetrahydrofuran (THF)
or diethyl ether. Replacement of hydroxide ion occures by
chloride ion with retention of configuration. This is 2nd order
reaction. RATE = k [1-Phenyl ethanol] [Thionyl Chloride]
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SN1’ (Unimolecular Nucleophilic substitution with acrylic
rearrangement)
Under SN1 reaction conditions allylic substrate produces
rearrangement product in addition to normal product. At the
1st step OH group of substrate is protonated & produce 1°
carbocation which will undergo rearrangement to form more
stable 2° carbocation. After that nucleophile will attack to
form final products. Rate depends on substrate
concentration only.
SN2’: (Bimolecular Nucleophilic Substitution with allylic
rearrangement)
Normal SN2 mechanism can’t occure here. Nucleophile will
face steric hindrance as the leaving group is attached with 3°
carbon. Therefore nucleophile will attack gamma carbon
atom & rearranged product will obtain.
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NEIGHBOURING GROUP PARTICIPATION (N.G.P):
When a nucleophilic group present in a substrate molecule
temporarily participates in substitution reaction before
attacking of other nucleophile present in reaction medium &
control the stereochemistry & rate of the reaction is known
as N.G.P.
The rate of enhancement due to N.G.P. is called Anchimeric
Assistance. N.G.P mechanism consists two SN2 substitution
(i.e. two times backside attack) So product will have
retention of the stereochemistry.
FEW EXAMPLES OF N.G.P.—
1.
When nucleophile concentration will be higher in reaction
medium then normal SN2 reaction will undergo & product
will be with inversion of configuration.
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But when low concentrated nucleophile will be used then
N.G.P will occure.
Silver ion here act as electrophilic catalyst & ease the
removal of bromine.
2. Due to less electronegativity & more polarizability of
sulphur atom it will act as nucleophile & follow N.G.P.
3. Halogen act as nucleophile in N.G.P.
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4. Phenyl group act as neighbouring group participant.
Acetolysis of recemic threo-3-phenyl-2-butyl modulate form
racemic threo mixture of product.
Erythro isomer also undergoes acetolysis reaction. Since in
the meso-phenonium ion the 2 methyl group are cis & in
active phenonium ion they are trans to each other. So later
phenonium ion is thermodynamically more stable than
former. So acetolysis of erythro isomer is faster than threo.
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5. In norbornene system N.G.P. occure through sigma & pi-
bond participation & formed nom classical carbocation
intermedate. Pi-bond participation is more prominent
than sigma-bond participation because energy of pi-
bonded electrons are in higher energy than sigma
bonded electrons. So donor ability of pi-electrons are
higher than sigma electrons.
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PHASE TRANSFER CATALYST:
The phase transfer catalyst is a compound that catalyzes a
reaction by transferring a reagent into the phase in which it is
needed.
Sodium cyanide can’t react with alkyl halide with out phase
transfer catalyst. Since Sodium cyanide is water soluble &
alkyl halide is water insoluble. If aqu solution of cyanide is
mixed with 1-chlorooctane in a nonpolar solvent then 2
separate layers are formed & reaction is not proceed. But
this reaction can occure if catalytic amount of phase transfer
catalyst, a quaternary ammonium salt is added which is
soluble in non polar solvent due to presence of nonpolar alkyl
group, and also soluble in polar solvent because of having
charge. So that it can act as mediator between two solvents.
CROWN ETHER:
A group of large ring polyethers having 3 dimensional crown
shape is said to be crown ether. Cyclic polyethers of ethylene
glycol, (OCH2CH2)n & are named in the form of x-crown-y,
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where x= the total no. of atoms in ring & y= the total no. Of
oxygen atoms.
Crown ether is able to form complex effectively by sharing
lone pair of oxygen with that particular cation which fits well
into its cavity. 18-crown-6 form strong complex with K+ ion.
This newly formed cation is lipophilic in nature & soluble in
org. solvent of low polarity. The cyanide ion is now free to
react.