ORGANIC CHEMISTRYREACTION MECHANISMS

(1) Substitution Nucleophilic Bimolecular (SN 2)Proposed by Edward Davis Hughes and Sir Christopher Ingold

(1937).The reaction between a primary halide and a nucleophile follows

second order Kinetics i.e., rate depends on the concentration of alkylhalide as well as nucleophile.

e.g. rate µ [alkyl halide] [nucleophile]

HO +

Solid wedge represents the bond coming out of the paper dashed line represent bond going down the paper and a straight line represent

bond in the plane of the paper.The incoming nucleophile interact with the alkyl halide causing the

C—X bond to break while forming a new C—OH bond. These twoprocesses takes place in a single step simultaneously and no intermediateis formed. Inversion of configuration takes place during the process.Carbon atom in the transition state is simultaneously bonded to fiveatom, therefore unstable and cannot be isolated.

Tertiary halides donot undergo SN2 mechanism due to steric hinderance.

Since the nucleophile attacks from opposite side of halide atom, thethree alkyl groups do not permit the nucleophile to attack on carbonatom, the order of reactivity followed is

Primary halide > Secondary halide > Tertiary halide

Nu: Nu: Nu: Nu:XX X

HH

HHHHH

H HC

C

C

tert-butyl 3°(0)

Isopropyl 2°(0.02)

Ethyl 1°(1)

Methyl(30)

X

HH

H

HH

H

HHH

H

H HHH

H

C

C C

(2) Substitution Nucleophilic Unimolecular (SN 1)Tertiary halide proceeds via SN1 mechanism. Rate of reaction depends

only on the concentration of alkyl haliderate µ [alkyl halide]

The reaction takes place in two stepsStep-I. The polarised C—X bond undergo slow cleavage to produce

a carbocation and a halide ion.

Br

Step-I is slowest and reversible.Step-II. The carbocation thus formed is attacked by nucleophile to

complete the substitution reaction.

Effect of Solvent : SN1 reactions are favoured in protic solvent (a)as step-I involves the C—Br breaking for which the energy is obtainedthrough solvation of halide ion with proton of protic solvent.

(b) Polar solvent promote ionization of halide ion.

Since the reaction proceeds through formation of carbocation, sogreater the stability of carbocation, faster will be the rate of reactiontherefore

Ph C Ph CH PhCH allyl CH C CH CH CH CH CH3 2 2 3 3 3 2 3 2 3Å Å Å Å Å Å Å> > > > > > >b g b g

For this reason allylic and benzylic halides show high reactivitytoward SN1 mechanism. The carbocation thus formed get stabilised throughresonance.

H C CH CH H C CH CH2 2 2 2= ¬®¾ =Å Å

— —

CHÅ

2 CH2 CH2 CH2Å

Å Å

For alkyl group, the reactivity of halides R—X follow the sameorder in both mechanisms.

R—I > R—Br > R—Cl > R—FVinyl halides neither undergo SN1 nor SN2 mechanism. SN 2 mechanism

is hindered by the fact that carbon atom attains a negative charge andSN1 mechanism is hindered by resonance and no ionization possible.

(3) Acid Catalysed Hydration of AlkeneAlkene reacts with H2O in presence of mineral acid as catalyst to

form alkenes. In unsymmetrical alkene the reaction proceed accordingto Markovnikov rule.

> = <+C C H O2H +

C C—H OH

CH H3CH = CH+ O —CH—CH2 2 3CH 3

OH

Step-1. Protonation of alkene to form carbocation by electrophilicattack of hydronium ion (H 3O+)

>C = C< + H—O—H —C—C— + H O 2

Å

H

HH

+ ::

SN2

1. SN2 reaction follow 2nd orderkinetics.

2. Inversion of configuration takesplace.

3. No effect of solvent.

SN1

SN 1 reaction follow first orderkinetics.Retention of configuration and alsoracemisation takes place.More polar sovlent more is the rateor reaction.

Step-2. Nucelophilic attack of water on carbocation.

Step-3. Deprotonation to form alcohol.

(4) Addition of Grignard Reagent on Carbonyl CompoundsStep-I. Nucleophilic addition of Grignard reagent to carbonyl group

to form an adduct.

> = + - ¾ ®¾

LNMMM

OQPPP

+ - + ++-

- +-C O R MgX C OM g X

d d d d d— — —

2

Bond in Grignard Reagent is highly polar carbon being non-metaland magnesium metal, So Mg reactes to oxygen to form adduct.

Step-II. Hydrolysis of adduct yield alcohol.

—C—O Mg X —C—OH + Mg+ –

– ++ –

R R X

OH

(5) Acid Catalysed Dehydration of AlcoholAlcohols undergo dehydration by heating with concentrated H 2SO4.

CH CH OH H C CH H OH SOK3 2

2 4443 2 2 2¾ ®¾¾ = +

R

Secondary and tertiary alcohols are dehydrated under milder conditions.

OH

CH CH CH CH CH CH H OH PO

K3 385% 3 4

443 3 2 2— — ¾ ®¾¾¾¾ = +

H C C OH CH C CH H OH P O

K320% 3 4

350 3 3 2— — — —¾ ®¾¾¾¾ +

CH3

CH 3 CH2

The reaction proceed in three steps—Step-1. Formation of protonated alcohol.

H SO H HSO2 4 4¾ ®¾ +Å

Step-2. Formation of carbocation : — It is the slowest step and ratedetermining step.

Step-3. Elimination of Proton.

The acid used in step-1 is released in step-3. To drive the equilibriumto the right ethene is removed fast.

(6) Reaction of Ether with HIStep-1. The reaction start with protonation of ether.

Step-2. Iodide is a good nucleophile. It attack the least substitutedcarbon atom of the oxonium ion formed in step-1 and displaces analcohol molecule by SN 2 mechanism. Thus in the cleavage of mixedethers with two different alkyl group, the lower alkyl group forms alkyliodide and larger forms alcohol.

I CH O CH CH I CH O CH CH CH I CH CH OH-Å Å

+ ® ¼ ¼ ¼

NMMM Q

PPP® +3 2 3 3 2 3 3 3 2— —HH

When HI is in excess and reaction is carried at high temperaturealcohol reacts with another molecule of HI to form another alkyliodide.

Step-3.

When one of the alkyl group is tertiary, the halide formed is atertiary halide.

H C C O CH HI CH OH CH C I3 3 3 3— — — —+ ¾ ®¾ +

CH3

CH 3

CH3

CH3

Due to formation of tertiary carbocation (stable).

H C C O CH HI H C C O CH CH OH CH CSlow3 3 3 3 3 3— — — — — —+ ¾ ®¾ ¾ ®¾ +

ÅÅ

CH3

CH 3

CH3

CH 3

CH3

CH3

H

CH C I CH C I SN3 31— — —Å + ¾ ®¾

CH3

CH 3

CH3

CH 3

In anisole :

+ HI + I

O CH— 3 H O C H— —+

3

The CH3—O bond is weaker then C6H5—O bond because the carbonatom of benzene ring is sp2 hybridised and there is a partial doublebond character. There attack of I break the CH3—O bond from CH3I .

H O CH I CH I— —¯+ ¾ ®¾ +3 3

OH

(7) Addition of HCN to >C = OThe reaction proceeds by attack of nucleophile.

> = + ¾ ®¾C O HCN COH

CN

Step-1. Generation of nucleophile.

HCN + OH : CN + H O 2

Step-2. Nucleophilic attack of CN – on carbonyl group.

CH COOH C H OH CH COOC H H OH SO3 2 5

2 43 2 5 2+ ¾ ®¾¾ +

(8) EsterificationStep-1. Protonation of carbonyl oxygen activate the carbonyl group

towards nucleophilic addition of alcohol. Proton transfer in the tetrahedral

intermediate convert the OH– group into -+FH IKOH2

Step-2. Transfer of Proton.

Step-3. OHÅ

2 is a better leaving group and eliminated as H2O.Protonated ester so formed finally loses a H+ (Proton) to give ester.

(9) MechanismAddition of NH3, NH2OH, NH 2NH2, C6H5NHNH2 or NH 2CONHNH2

to >C = O.Step-1. Addition of ammonia derivative to >C = O

Step-2. Elimination of H 2O to form product.Where X = – H, —R, —OH, —CONHNH2 or —NHC6H5

The pH of the reaction is controlled at 3.5, in strongly acidic mediumproton is captured by amino grup to form salt

RNH H RNH..

2 3+ ¾ ®¾ÅÅ

In basic medium, OH – cannot attack to electro-negative oxygenatom.

> = + ¾ ®¾+ - -

C O OH No reactiod d

n

Hence no product is formed in strongly acidic or basic medium.

(10) Some Important Reactions(A) Friedel Craft Reaction

Addition of alkyl (R) or aryl group (COR) to benzene nucleus inpresence of Anhydrous AlCl 3 (Lewis acid).

(a) Alkylation —

+ CHCl + HCl3Anhy. AlCl

CH3

(b) Acetylation or Acylation —

+ CHCOCl + HCl3

COCH3

Anhy. A lCl

CHCO3

CHCO3

+ O

COCH 3

+ HClAnhy. AlCl

(c) Benzoylation —

+ C HCOCl6 5

COC H 65

+ HCl

MechanismStep-I. Generation of electrophile, AlCl 3 is Lewis acid and generate

electrophile.

CH Cl AlCl AlCl C H3 3 4 3+ ¾ ®¾ +Å

Step-II. Formation of intermediate.

Step-III.

+

CH3H

+ AlCl4 + AlCl +HCl 3

CH3

Characteristics :(1) More stable carbocation will form the product. e.g.

(2) Phenol and aniline form addition product with AlCl 3 donotform carbocation.

(3) Chlorobenzene and vinyl cloride do not form carbocation.(4) Addition product will be determined by ortho, meta and para

directing group e.g.

+ CHCl 3A lCl CH +3 + HCl

CH3

CH3CH3CH3

(B) Aldol Condensation

(C) Cross Aldol Condensation Reaction

Aldehyde and ketones having one or more –H-atom when warmed with dilute base undergo self addition reaction known as aldol condensation.

Whatever be the size of aldehyde, attack comes from –H-atom and product is .

Ketones also undergo self addition to form ketol.

When two different aldehydes are condensed together 4 products are formed.

a

a

b

CH CH O H CH CHO CH CH CH CHONaOH3 2 3 2= + ¾ ®¾¾: — —

OH

Mechanism :

Cross Aldol Involving Aldehyde and Ketone

(D) Cannizzaro Reaction

Step-I.

Step-II.

Step-III.

Formation of carbanion.

–H-atom is removed by base as H O.

Disproportionation of an aldehyde lacking –H-atom like HCHO, CH CHO, RC—CHO to salt of an acid and a primary alcohol is known as Cannizzaro Reaction.

a

a

2

6 5 3

CH CH CH O H CH CHO CH CH CH CH CHONaOH3 2 2 3 2 2= + ¾ ®¾¾— — — —

OH

CH CH O OH CH CH O CH CH O H O3 2 2 2= + = ¬ ®¾ = +- -

— —

CH CH O CH CHO CH CH CH CHO3 2 3 2= + ¾ ®¾ — — —

O–

O– OH

CH CH CH CHO CH CH CH CHO OHH OH3 2 3 2— — —

+ - -¾ ®¾ ¾¾ +

OHO O

CH CH O H CH C CH CH CH CH C CHOH3 2 3 3 2 3= + ¾ ®¾¾

-— — — — — —

2 3HCHO NaOH CH OH HCOONa+ ¾ ®¾ +

Mechanism :Step-I.

Step-II.

Reversible addition of OH to >C = O.

Transfer of hydride ion (H ) to another aldehyde.

–

–

2 + NaOH +

COONaCHOH2CHO

2 3 3 2 3CH C CHO NaOH CH C CH OH CH C COONa— — — — — —+ ¾ ®¾ + +

CH3

CH3

CH3

CH3

CH3

CH3

–

H

OH

C H CH O OH C H C O6 5 6 5— — —= + ¾ ®¾-

C H C O C C H C H C O H C C HSlow6 5 6 5 6 5 6 5— — — — — —+ ¾ ®¾¾ = +

H

OH

H

O–OHO

H Step-III

C H C O C H CH OH6 5 6 5 2— — —+

O

Step-III. The acid and alkoxide ion so obtained involve in proton exchange to yield more stable product of salt and alcohol. Similarly

“In addition of HX molecule to an unsymmetrical alkene, H-atom goes to the C-atom which has already larger no of H-atoms attached to it.”

1. The molecule to be added is known as addendum e.g.

2. The positive part of adendum goes to the carbon atom which has already larger number of H-atoms attached to it.

3. The negative part of addendum goes to the C-atom which has lesser no of H-atoms attached to it.

Markownikov’s Rule (MKR)

H C H OH H C H H C H H OOH— — — — — —+ ¾ ®¾ ¾ ®¾¾ +- -

2

O–

OH

O–O

O–

H C H C O H C CH OH— — —+ = ¾ ®¾ + 3

O

O–O–

O–

H

H

H Cl HBr H I HF HCN H NO HH SO H OC l+ - + - + - + - + - + - + - - +, , , , , , ,3 4

CH CH CH H Br CH CH CH3 2 3 3— —= + ¾ ®¾

Br

4. When the reaction is carried in presence of some peroxide, the product is reverse of MKR, called Kharasch or peroxide effect.

MKR proceed via carbocation formation—1. Larger alkyl group polarise the -bond

2. attack first and generate secondary carbocation.3. Br attack to carbocation to form product.Another example is

Peroxide effect proceed via free radical mechanism

One free radical always generate another free radical

Mechanism—

p

–

l l l

CH CH CH HBr CH CH CH BrPeroxide

Benzoyl3 2 3 2 2= + ¾ ®¾ ¾¾

CH CH CH H CH CH CH CH CHCHBr3 3 3 3 3

¾ ®¾ + -Å

Å= + ¾ ®¾ ¾ ®¾

d d— —

Br

HÅ

CH CH CH CHCH H CH CH CHCH CH CH CH CHCHBr3 2 3 3 3 2 3 3 2 2

dd dd+ - + Å -= + ® ¾ ®¾ —

Br

CH3

C H C O O C C H C H C O C H COhv6 5 6 5 6 5 6 5 22— — — — — — —

• •¾ ®¾ ¾ ®¾ +

OOO

C H HBr C H Br• •

6 5 6 5+ ¾ ®¾ +

CH CH CH Br CH CHCH Br CH CH CH Br BrHBr3 2 3 2 3 2 2= + ¾ ®¾ ¾ ®¾¾ +

• • •