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SUBSTITUTION NUCLEOPHILIC REACTION

SN1: (Substituition Nucleophilic Unimolecular)

The reaction occure through these 2 steps. In the 1st step liberates from the substrate (t-butyl bromide) to form stable . This is the slowest (RATE DETERMINING STEP). This is an endothermic process. In the 2nd step ( 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. 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 . The driving force of SN1 reaction is the formation of stable carbocation. Mesomeric (+M) effect, & (+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 : 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 ( 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 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 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 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 ] [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 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.