substituition nucleophilic unimolecular) · compounds undergo faster sn2 mechanism instead of sn1....

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SUBSTITUTION NUCLEOPHILIC REACTION SN1: (Substituition Nucleophilic Unimolecular) The reaction occure through these 2 steps. In the 1 st 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 2 nd 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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  • 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.

  • 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

  • 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

  • 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

  • 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.

  • 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

  • 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.

  • 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.

  • 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.

  • 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]

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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,

  • 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.